3,

Si pc-funu RccurJi dealer

E K E \K OThtR.

SALEM ACRES BASELINE HEALTH RISK ASSESSMENT

VOLUME II APPENDICES

May 29, 1992

URS CONSULTANTS 3605 Warrensville Center Bead, Cleveland, Ohio 44122 (216) 283-4000

INTRODUCTION

The lexicological profiles have been divided into two sections within this volume. Section A contains general profiles, and Section B contains technical profiles. The general profile of a compound has been written for non-chemists/non-toxicologists and is intended to give the reader a feel for what a compound is, where it may have come from, and what health effects it may cause. No attempt has been made to present data, dosages, or risk coefficients within the general profiles section. The use of technical terminology has been kept to a minimum, although some terms have been included. Technical profiles provide a summary of the available coefficients used to calculate risk, and the lexicological evidence that was used to develop those coefficients and to classify the compound. A listing of literature cited is presented at the end of the technical profile section.

TABLE 14 SUMMARY OF CONTAMINANTS DETECTED ONSITE

FRACTION

VOCs

Semi-VOCs

Dioxins/ Furans

MEDIUM OF OCCURRENCE FOR EACH COMPOUND PARAMETER SLUDGE SOIL GROUND SURFACE FISH

WATER WATER SEDIMENT TISSUE Methylene Chloride X X Acetone X X X Carbon Disulfide X trans-1 ,2-Dichloroethene X 2-Butanone X 1,1,1-Trichloroethane X Trichloroethene X X Benzene X X X Tetrachloroethene X Toluene X X X Chlorobenzene X Ethybenzene X X X Total Xytenes X X X X 1 ,3-D'chlorobenzene X 1 ,4-Dchlorobenzene X Benzyl Alcohol X 1 ,2-Dichlorobenzene X 2-Methylphenol X 4-Methylphenol X X 2,4-Dimethvlphenol X Benzole Acid X X X Naphthalene X X X X 2- Methylnaphthalene X X X X Dimethyl phthalate X Acenaphthylene X X Acenaphthene X Dibenzofuran X Diethyl phthalate X Fluorene X X X 4-Nitroaniline X N- N itrosodi phenylam ine X X Hexachlorobenzene X Phenanthrene X X X Anthracene X X Di-n-Butyl phthalate X Fluoranthene X X X Pyrene X X X Butyl benzyl phthalate X Benzo (a) anthracene X X Chrysene X X bis(2-ethylhexyl) phthalate X X Di-n-Octyl phthalate X Benzo (bLFIuoranthene X X X Benzo (k) Fluoranthene X X X Benzo (a) pyrene X X lndeno(1 ,2,3-c,d) pyrene X X Dibenzo (a, h) anthracene X X Benzo(ah,i)pervtene X X 2,3,7,8-TCDD Equivalent X

TABLE 14 SUMMARY OF CONTAMINANTS DETECTED ONSITE

MEDIUM OF OCCURRENCE FOR EACH COMPOUND FRACTION PARAMETER SLUDGE SOIL GROUND SURFACE FISH

Pesticides/ Endosultan I X WATER WATER SEDIMENT TISSUE

X PCBs 4,4'-DDE X X X

4,4'-DDD X X X 4,4' -DDT X Aroclor-1254 X X Aroclor-1260 X X

Metals Aluminum X X X X X

Calcium X X X X X X

Copper X X X X X Iron X X X X X X Lead X X X X X X

Manganese X X X X X X

Potassium X X X X X

Zinc X X X X X X

Antimony X Arsenic X X X X Barium X X X X X X Beryllium X X Cadmium X X

Chromium X X X X X Cobalt X X X

Magnesium X X X X X X

Mercury X X X Nickel X X X

Selenium X X X X X Silver X X Sodium X X X X X Thallium X Vanadium X X X X

Cyanides (Total) X Titanium X

f

APPENDIX "A"

(ieneral Toxicity Profiles

GENERAL PROFILE

METHYLENE CHLORIDE

Methylene chloride is used as an extractant of substances which are affected by high temperatures. It can also be used as a solvent for oils, fats, waxes, esters, paint remover, and a degreaser. It can be inhaled, absorbed through the skin, ingested, and irritate the eyes and skin. Repeated contact with methylene chloride may cause a dry, scaly, and fissured dermatitis. Liquids and vapors are irritating to the eyes and respiratory tract at higher concentrations. If the liquid is held in contact with the skin, it may cause burns. Methylene chloride is a mild narcotic. Effects from intoxication include headache, giddiness, stupor, irritability, numbness, and tingling in the limbs. Irritation to the eyes and upper respiratory passages occurs at higher doses. In severe cases, observers have noted toxic encephalopathy with hallucinations, pulmonary edema, coma, and death. Cardiac arrhythmias has been produced in animals but has not been common in human experiences. Exposure to this agent may cause elevated carboxyl hemoglobin levels that may be significant in smokers, workers with anemia or heart disease, and those exposed to carbon monoxide.

GENERAL PROFILE

ACETONE

Acetone is a colorless liquid with a sweetish odor. It is used as a solvent in the production of lubricating oils, and in the manufacturing process for pesticides, Pharmaceuticals, and chloroform. The chemical has not been evaluated by the U.S. EPA for the evidence of human carcinogenic potential. It can be inhaled, ingested, or have contact with the skin and eyes. It may affect the respiratory system and the skin. It is moderately toxic by various routes and can be narcotic in high concentrations. Inhalation may produce headache, fatigue, excitement, and bronchial irritation. Serious poisoning is rare. Prolonged or repeated topical use may cause erythema and dryness (Merck, 1983).

GENERAL PROFILE

CARBON BISULFIDE

Carbon disulfide, CS2, is a clear colorless liquid which in pure form has a sweet odor and in commercial and reagent grades has a fowl smell (rotten eggs). Carbon disulfide is used in the manufacture of soil disinfectants and vacuum tubes. It is also used as a solvent for cleaning and extractions, especially in metal treatment and plating. It is a fumigant for commodities, a corrosion inhibitor, and inhibits polymerization for vinyl chloride (IRIS, 1990)., Carbon disulfide has not been evaluated by the U.S. EPA for evidence of human carcinogenic potential. Carbon disulfide is toxic and affects the central nervous system, cardiovascular system, eyes, kidneys, liver, and skin. It may be absorbed through the skin as a vapor or liquid, inhaled, or ingested. Alcoholics and those suffering from neuropsychic trouble are at special risk (LeFaux, 1968). In acute poisoning, early excitation of the central nervous system occurs, followed by depression with stupor, restlessness, and unconsciousness. If recovery occurs, the patient usually passes through the after stage of narcosis with nausea, vomiting, headache, etc. (Sax/Lewis, 1984). Also possible are motor disturbances of the bowel, anemia, disturbances of cardiac rhythm, loss of weight, polyuria, and menstrual disorders. The probable oral lethal dose for a human is between 0.5 and 5 g/kg or between one ounce or one pint for a 70-kg (150 Ib) person (Gosselin et al., 1976).

GENERAL PROFILE

TRANS-1.2. DICHLOROETHENE

1,2 Dichloroethene is an ethereal liquid with an acrid odor. It gradually decomposes in air in the presence of light and moisture releasing hydrochloric acid as a by-product. It is used as a solvent for fats, phenol, camphor, etc. Inhalation of vapors causes respiratory irritation and narcosis.

GENERAL PROFILE

2-BUTANONE

2-Butanone, otherwise known as methyl ethyl ketone (MEK), is a colorless flammable liquid. It is used as a solvent and a fumigant, and in the manufacture of Pharmaceuticals. MEK is not classified as a carcinogen. MEK can be inhaled, ingested, or irritate the skin and eyes. It is moderately toxic if ingested or absorbed through the skin. It is a strong irritant and affects the peripheral and central nervous systems. It also affects the eyes at low concentrations.

GENERAL PROFILE

1.1.1-TRICHLOROETHANE

1,1,1-Trichloroethane is a colorless, nonflammable liquid with an odor similar to chloroform. It has ben used as a substitute for carbon tetrachloride. In liquid form, it is used as a degreaser and for dip cleaning and bucket cleaning of metals. It is also used as a dry cleaning agent, a vapor degreasing agent, and a propellant. 1,1,1-Trichloroethane can affect the skin, eyes, cardiovascular system, and central nervous system. Liquid and vapors are irritating to eyes on contact. This effect is usually noted in acute exposure cases. Repeated skin contact may produce a dry, scaly, and fissured dermatitis, due to the solvent's defatting properties. 1,1,1-Trichloroethane acts as a narcotic and depresses the central nervous system. Acute exposure symptoms include dizziness, incoordination, drowsiness, increased reaction time, unconsciousness, and death.

GENERAL PROFILE

TRICHLOROETHENE

Trichloroethene is a solvent used for fats, waxes, resins, oils, rubber, paint, and varnishes. TCE may affect the respiratory system, heart, liver, kidneys, skin, and central nervous system (CNS). Exposure to trichloroethene may cause irritation to the eyes, nose, and throat. Repeated skin contact with TCE liquid may cause dermatitis. Acute exposure to TCE depresses the CNS, exhibiting such symptoms as headache, dizziness, vertigo, tremors, nausea and vomiting, irregular heartbeat, sleepiness, fatigue, blurred vision, and intoxication similar to that of alcohol. Alcohol consumption may worsen TCE symptoms. A form of addiction has been observed in exposed workers.

GENERAL PROFILE

BENZENE

Benzene is a chemical which is classified as a human carcinogen. The EPA classification known as weight of evidence for carcinogenicity is Group A: a human carcinogen with sufficient evidence from studies to support a causal association between the chemical and cancer in humans. Benzene is usually inhaled as a vapor, ingested, and can irritate the skin and eyes. It adversely affects the blood-making processes in the body and has shown to be poisonous to the fetus. It is known to cause leukemia in individuals and lethal to developing organisms in animals (IRIS, 1989).

GENERAL PROFILE

TETRACHLOROETHENE

Tetrachloroethene is a man-made substance widely used for dry cleaning fabrics and textiles and for metal-degreasing operations. It is also used as a starting material (building block) for the production of other man-made chemicals. Although tetrachloroethylene is a liquid at room temperature, some of the liquid can be expected to evaporate into the air producing an ether-like odor; evaporation increases as temperature increases. In high concentrations in air, particularly in closed, poorly ventilated areas, single exposures to tetrachloroethene can cause central nervous system effects leading to dizziness, headache, sleepiness, confusion, nausea, difficulty in speaking and walking, and possibly unconsciousness and death. The potential long-term health effects that might occur in humans from breathing lower levels of tetrachloroethene than those that produce CNS effects or from ingesting very low levels of the chemical found in some water supplies have not been identified.

GENERAL PROFILE

TOLUENE

Toluene is a colorless liquid used in the manufacture of benzene. It is derived from coal tar, and commercial grades usually contain small amounts of benzene as an impurity. It is used as chemical feed, as a solvent for paints and coatings, or as a component of automation and aviation fuels. Toluene is less toxic than benzene. Toluene is toxic when inhaled, ingested, or absorbed through the skin. It is a skin and eye irritant. Repeated or prolonged contact with liquid may cause removal of natural fats and oils from the skin, resulting in dry skin or inflammation of the skin. Acute exposure to toluene results in central nervous system depression. Symptoms and signs include headache, dizziness, fatigue, muscular weakness, drowsiness, collapse, and coma with higher concentrations. Enlarged livers can be found among exposed individuals.

GENERAL PROFILE

CHLOROBENZENE

Chlorobenzene is a colorless refractive liquid that is used in the manufacture of aniline, phenols, and as an intermediate in the manufacture of dyes and many pesticides. This substance can be toxic when inhaled, ingested, or when it comes into contact with the eyes and skin. It can have an effect on the respiratory and central nervous system, the liver, skin, and eyes. It is moderately toxic by ingestion. It is also a strong narcotic with slight irritant qualities. Little is known of the effects of repeated exposure at lower concentrations, but it may cause kidney and liver damage. Large quantities cause a state of unconsciousness in guinea pigs followed by death. Prolonged exposure may cause kidney and liver damage. Also sleepiness, loss of consciousness, twitching of the extremities, discoloration of the skin, deep, rapid respirations, and a small irregular pulse are the chief symptoms occurring in acute exposures. Urine may be red, and the red blood cells show degenerative and regenerative changes.

GENERAL PROFILE

ETHYLBENZENE

Ethylbenzene is a colorless liquid with a pungent aromatic odor (Sittig, 1985). It is used in the manufacture of sryrene, synthetic rubber, and is also a solvent and a component of automotive and aviation gasoline. Ethylbenzene is toxic when inhaled, ingested, or when it contacts the eyes and skin. Harmful effects include kidney disease, liver disease, chronic respiratory disease, and skin disease. Since Ethylbenzene is metabolized by the liver, concern is expressed for the tissue. It may cause dermatitis, narcosis, and coma. Pathological findings identified congestion of the brain and lungs (Sax/Lewis, 1987).

GENERAL PROFILE

TOTAL XYLENES

Xylene is used as a solvent, as a constituent of paint, lacquers, varnishes, inks, dyes and adhesives, cements, cleaning fluid and aviation fuels, and as a chemical feedstock used in the manufacture of plastic materials and synthetic textile fabrics. Xylene is also used in the manufacture of hydrogen peroxide, perfumes, insect repellents, epoxy resins, and in the leather industry. Xylene can affect the central nervous system (CNS), eyes, gastrointestinal tract, blood, liver, kidneys, and skin. Xylene vapor may cause irritation of the eyes, nose, and throat. Repeated or prolonged skin contact with xylene may cause drying and defatting of the skin, which may lead to dermatitis. Liquid xylene is irritating to the eyes and mucous membranes, and aspiration may cause chemical pneumonitis, pulmonary edema, and hemorrhage. Repeated exposure of the eyes to high concentrations of xylene vapor may cause reversible eye damage. Acute exposure to xylene vapor may cause CNS depression and minor reversible effects on the liver and kidneys. At high concentrations, xylene vapor may cause dizziness, staggering, drowsiness, and unconsciousness. Also at high concentrations breathing xylene vapors may cause anorexia, nausea, vomiting, and abdominal pain.

GENERAL PROFILE

1.3-DICHLOROBENZENE

1,3-Dichlorobenzene is one of a group of chlorinated benzene compounds. These compounds are rarely found in their pure form, but usually occur as mixtures. They are by-products of the manufacture of dyes and pesticides. Although little is known about the toxicity or health effects of 1,3-dichlorobenzene alone, it is thought that the effects are generally similar to those of chlorobenzene.

GENERAL PROFILE

1.4-DICHLOROBENZENE

There are three isomeric forms; 1,2-dichlorobenzene is a yellow liquid with aromatic odor; 1,3-dichlorobenzene is a colorless liquid,; 1,4-dichlorobenzene is a colorless solid with mothball-like odor. Routes of exposure are inhalation, ingestion, and dermal contact. Human exposure to dichlorobenzene is reported to cause hemolytic anemia and liver necrosis, and 1,4-dichlorobenzene has been found in human adipose tissue and causes liver cancer in mice. In addition, the dichlorobenzenes are toxic to nonhuman mammals, birds, and aquatic organisms and impart an offensive taste and odor to water. The dichlorobenzenes are metabolized by mammals, including humans, to various dichlorophenols, some of which are as toxic as the dichlorobenzenes. Chronic exposure by inhalation causes decreased body weight gain. Oral exposure effects the liver.

GENERAL PROFILE

BENZYL ALCOHOL

In the pure form benzyl alcohol is an aromatic white crystal. It is moderately toxic by ingestion and is a mild allergin and skin irritant. Long term ingestion of small amounts results in irritation and malaise in humans.

GENERAL PROFILE

1.2 DICHLOROBENZENE

1,2-Dichlorobenzene is a colorless to pale yellow liquid with a pleasant aromatic odor. It is used as a solvent for waxes, gums, resins, tars, rubbers, oils, asphalt; an insecticide for termites; a fumigant; a degreasing agent for metal, leather, and wool; an ingredient of metal polishes; and as an intermediate in the manufacture of dyes (Merck, 1985). 1,2-Dichlorobenzene can be ingested, inhaled, and absorbed by the skin. It is classified by the U.S. EPA to be considered as a human carcinogen. This does not imply that this chemical is necessarily a carcinogen. 1,2-Dichlorobenzene is a poison when swallowed and digested or mixed and passed through the blood. It is moderately toxic when breathed. 1,2-Dichlorobenzene can cause liver and kidney damage. High concentrations cause central nervous system depression. Symptoms may include irritation of eyes and nose and skin blistering (Sittig, 1985).

GENERAL PROFILE

2-METHYLPHENOL

2-Methylphenol, also known as o-cresol, is usually found in a mixture of compounds obtained from distillation of coal tar. Cresol was used as a germicide in Britain where it is known as lysol. Long term effects from ingestion of small quantities of cresol causes decreased body weight, kidney and liver malfunctions, and nervous system disorders. 2-Methylphenol is rated by EPA as every toxic compound with a lethal dose of about one ounce for a 150 pound human. Contact with the skin causes dermatitis, and serious or fatal poisoning can result if large areas of the skin are wet with cresol compounds and are not removed. Ingestion of even a small amount can cause paralysis and coma.

GENERAL PROFILE

4-METHYLPHENOL

4-Methylphenol (p-Cresol), (C7H8O), is used as a disinfectant, and as an intermediate in the manufacture of chemicals, dyes, plastics, and antioxidants. p-Cresols can be inhaled or absorbed through liquids and vapors, ingested, and irritate eyes and skin; it is corrosive to all tissues. It may cause burns, weakness of muscles, headaches, dizziness, dimness of vision, loss of consciousness, ringing in the ears, and sometimes death. Chronic or repeated absorption through skin, mucus membranes, or respiratory tract may cause systemic poisoning. Vomiting, difficulty in swallowing, salivation, diarrhea, loss of appetite, headache, fainting, dizziness, mental disturbances, and severe damage to the liver and kidneys may also occur. Decreased body weights and neurotoxicity are evidenced through subchronic and neurotoxicity studies (U.S. EPA, 1987).

GENERAL PROFILE

2.4-DIMETHYL PHENOL

2,4-Dimethyl phenol is usually found in coal tar creosote, a mixture of compounds obtained from the distillation of coal. Coal tar creosote is a wood preservative widely used on utility poles and railroad ties. It has similar toxicological effects to phenol. It burns the skin if contacted, and is poisonous if taken internally.

GENERAL PROFILE

BENZQIC ACID

Benzoic acid occurs in nature in free and combined forms. It is used in preserving foods, fats, fruit juices, dyes, for curing tobacco, and as a standard in chemical analysis. It can be inhaled, injected, or absorbed through the skin. This substance is poisonous if inhaled as a vapor. It is moderately irritating to human skin, eyes, and mucous membranes.

GENERAL PROFILE

NAPHTHALENE

Pure naphthalene is a white crystallized solid with characteristic mothball odor. Exposure is through skin absorption and ingestion. Naphthalene is a non-carcinogenic PAH. Naphthalene is primary irritant and causes erythema and dermatitis upon repeated contact. It is also an allergen and may produce dermatitis in hypersensitive individuals. Direct eye contact with the dust has produced irritation and cataracts. Chronic oral exposure results in ocular and internal lesions. Initial symptoms include eye irritation, headache, confusion, excitement, malaise, profuse sweating, nausea, vomiting, abdominal pain, and irritation of the bladder. There may be progressive jaundice, hematuria, hemoglobinuria, renal tubular blockage, and acute renal shutdown. Hematologic features include red cell fragmentation, icterus, severe anemia with nucleated red cells, leukocytosis, and dramatic decreases in hemoglobin, hematocrit, and red cell count.

GENERAL PROFILE

2-METHYLNAPHTHALENE

2-Methylnaphthalene is a poly cyclic aromatic hydrocarbon compound (PAH). It is formed when fossil fuels, garbage, or any plant or animal material is burned, and, therefore, it is usually found in smoke and soot. 2-methylnaphthalene is found in cigarette smoke, power plant emissions, and coal tar pitch. It causes numbness and erosion of tissues.

GENERAL PROFILE

DIMETHYL PHTHALATE

Dimethyl phthalate is a member of a group of chemicals called phthalic acid esters. These compounds are used as solvents, fixatives in perfumes, pesticides, and plasticizers. They are irritants to mucous membranes and are central nervous system depressants. Dimethyl phthalate is classified as slightly toxic by EPA. Symptoms of oral exposure include a burning sensation on the lips, tongue, and mouth, vomiting, diarrhea, paralysis, and coma. Inhalation of airborne dimethyl phthalate produces the same symptoms plus coughing and conjunctivitis.

GENERAL PROFILE

ACENAPHTHYLENE

Acenaphthylene is one of the poly cyclic aromatic hydrocarbon (PAH) compounds. Because it is formed when gasoline, garbage, or any animal or plant material burns, it is usually found in smoke and soot. This chemical combines with dust particles in the air and is carried into water and soil and onto crops. Acenaphthylene is found in coal tar pitch used by industry as an adhesive. People may be exposed to acenaphthylene from environmental sources such as air, water, and soil, and from cigarette smoke and overcooked food. Typical exposures are not usually to acenaphthylene alone, but to a mixture of similar chemicals. These mixtures cause numbness, skin and mucous membrane burns, and are eye and respiratory irritants.

GENERAL PROFILE

ACENAPHTHENE

Acenaphthene is one of the polycyclic aromatic hydrocarbon (PAH) compounds. Because it is formed when gasoline, garbage, or any animal or plant material burns, it is usually found in smoke and soot. This chemical combines with dust particles in the air and is carried into water and soil and onto crops. Acenaphthene is found in coal tar pitch used by industry as an adhesive. PAHs cause skin burns and numbness.

GENERAL PROFILE

DIBENZOFURAN

Dibenzofuran is formed as a byproduct in the manufacture of chlorinated herbicides, and is produced during the combustion of PCBs. It is not found in a pure form, but as a component of mixtures of dioxins and furans produced in a similar fashion.

GENERAL PROFILE

DIETHYL PHTHALATE

Diethylphthalate (DEP) is a clear, colorless liquid used as a solvent for cellulose esters; as a vehicle in pesticidal sprays; as a fixant and solvent in perfumery; as an alcohol denaturant; and as a plasticizer in solid rocket propellants. DEP has few acute and chronic toxic properties and seems to be devoid of any major irritating or sensitizing effects on the skin. Exposure to heated vapors may produce irritation of the nose and throat. Conjunctivitis, necrosis, respiratory tract irritation, dizziness, nausea, and eczema are symptoms cited by others. DEP has been shown to produce mutagenic effects. DEP is moderately toxic by ingestion and other routes and can be narcotic in high concentrations.

GENERAL PROFILE

FLUORENE

Fluorene is one of the poly cyclic aromatic hydrocarbon (PAH) compounds. Because it is formed when fossil fuels, garbage, or any other plant or animal material is burned, it is usually found in smoke and soot. This chemical combines with dust particles in the air and is carried into water and onto soil and crops. Fluorene is found in coal tar pitch used by industry as an adhesive. Although there are no human data that specifically link exposure to fluorene with human cancers, it is a component of mixtures that have been associated with human cancer. These include coal tar, soots, coke oven emissions, over cooked food and tobacco smoke. Exposure can cause numbness and results in skin burns.

GENERAL PROFILE

4-NITROANILINE

4-Nitroaniline most often occurs in industry as a by-product in the manufacture of aniline. These compounds are usually used as intermediates in the production of other chemicals, but are also found in products such as paints, varnishes, inks, dyes, and shoe polish. Poisonings by pure 4-nitroaniline are rare except in industrial settings. Ingestion of large amounts can cause coma and shock. Milder poisonings can result from skin contact or inhalation of vapors. Symptoms include weakness, headache, and vomiting. Long term exposure to small quantities can result in cyanosis (seen as a blueing of the fingers and lips), blood disorders, heart problems, as well as weakness, headache, and vomiting.

GENERAL PROFILE

N-NITROSODIPHENYLAMINE

N-nitrosodiphenylamine is structurally related to carcinogenic nitrosamines. Human exposure to nitrosamines results from contact with mixtures containing these compounds (e.g., cutting oils, tobacco products). Because of potential confounding by the other substances in these mixtures, data are of limited use in the evaluation of carcinogenicity of individual nitrosamines.

GENERAL PROFILE

HEXACHLOROBENZENE

Most of the hexachlorobenzene, (HCB) in the environment comes from agricultural processes. This substance progressively multiplies cells under conditions that do not develop normal cells. It also produces cancer-causing substances, tumors, and physical defects in developing embryos. HCB is a suspected human carcinogen. HCB can be inhaled, ingested, or affect the eyes and skin upon contact. Clinical manifestations include weight loss, enlargement of thyroid and lymph nodes, skin photosensitization, and abnormal growth of body hair. Skin sores and skin discoloration were associated with accidental consumption of HCB-contaminated seed grain. Cutaneous porphyria may result from prolonged periods of ingestion.

GENERAL PROFILE

PHENANTHRENE

Phenanthrene is one of the poly cyclic aromatic hydrocarbon (PAH) compounds. Because it is formed when gasoline, garbage, or any animal or plant material burns, it is usually found in smoke and soot. This chemical combines with dust particles in the air and is carried into water and onto soil and crops. Phenanthrene is found in coal tar pitch used by industry as an adhesive. People may be exposed to phenanthrene from environmental sources such as air, water, and soil, and from cigarette smoke and overcooked food. Typical exposures are not usually to phenanthrene along, but to a mixture of similar chemicals. Dermal exposures can result in skin burns and numbness.

GENERAL PROFILE

ANTHRACENE

Anthracene is one of the polycyclic aromatic hydrocarbon (PAH) compounds. Because it is formed when gasoline, garbage, or any animal or plant material burns, it is usually found in smoke and soot. This chemical combines with dust particles in the air and is carried into water and soil and onto crops. Anthracene is found in coal tar pitch used by industry as an adhesive. People may be exposed to naphthalene from environmental sources such as air, water, and soil, and from cigarette smoke and overcooked food. Typical exposures are not usually to anthracene alone, but to a mixture of similar chemicals. Dermal exposure can result in skin burns and numbness.

GENERAL PROFILE

DI-N-BUTYL PHTHALATE

Di-N-butyl phthalate is an oily liquid used as an insect repellent for the impregnation of clothing. It is toxic when ingested.

GENERAL PROFILE

FLUORANTHENE

Fluoranthene is one of the poly cyclic aromatic hydrocarbon (PAH) compounds. Because it is formed when gasoline, garbage, or any animal or plant material burns, it is usually found in smoke and soot. This chemical combines with dust particles in the air and is carried into water and onto soil and crops. Fluoranthene is found in coal tar pitch used by industry as an adhesive. People may be exposed to fluoranthene from environmental sources such as air, water, and from tobacco smoke and overcooked food. Typical exposures are not usually to chrysene alone, but to mixtures of similar compounds. Dermal exposure results in skin burns and numbness.

GENERAL PROFILE

PYRENE

Pyrene is absorbed by the skin and is a skin irritant. Workers exposed to 3 to 5 mg/m3 of pyrene exhibited some teratogenic effects. Pyrene is a polycyclic aromatic hydrocarbon (PAH). The acute toxicity of pure PAHs appears low when administered orally or dermally to rats or mice. Human exposure to PAHs is almost exclusively via the gastrointestinal and respiratory tracts, and approximately 99 percent is ingested in the diet. Despite the high concentrations of pyrene to which humans may be exposed through food, there is currently little information available to implicate diet-derived PAHs as the cause of serious health effects.

GENERAL PROFILE

BUTYL BENZYL PHTHALATE

Butyl benzyl phthalate is a member of a group of chemicals called phthalic acid esters. These compounds are used as solvents, fixatives in perfumes, pesticides, and plasticizers. They are irritants to mucous membranes and are central nervous system depressants. Butyl benzyl phthalate causes enlargement of the liver and kidneys if ingested in small quantities over a long period of time.

GENERAL PROFILE

BENZO(A)ANTHRACENE

Benz(a)anthracene is one of the polycyclic aromatic hydrocarbon (PAH) compounds. Because it is formed when gasoline, garbage, or any animal or plant material burns, it is usually found in smoke and soot. This chemical combines with dust particles in the air and is carried into water and onto soil and crops. Benz(a)anthracene is found in coal tar pitch used by industry as an adhesive. People may be exposed to benz(a) anthracene from environmental sources such as air, water, and soil, and from cigarette smoke and overcooked food. Typical exposures are not usually to benz(a) anthracene alone, but to a mixture of similar chemicals. Current theories on mechanisms of metabolic activation of polycyclic aromatic hydrocarbons are consistent with a carcinogenic potential for benz(a)anthracene. Benz(a)anthracene has a "bay-region" structure. It is metabolized by mixed function oxidases to reactive "bay-region" diol epoxides that are mutagenic in bacteria and tumorigenic in mouse skin painting assays.

GENERAL PROFILE

CHRYSENE

Chrysene is one of the poly cyclic aromatic hydrocarbon (PAH) compounds. Because it is formed when gasoline, garbage, or any animal or plant material burns, it is usually found in smoke and soot. This chemical combines with dust particles in the air and is carried into water and onto soil and crops. Chrysene is found in coal tar pitch used by industry as an adhesive. People may be exposed to chrysene from environmental sources such as air, water, and from tobacco smoke and overcooked food. Typical exposures are not usually to chrysene alone, but to mixtures of similar compounds. Current theories on mechanisms of metabolic activation of polycyclic aromatic hydrocarbons are consistent with a carcinogenic potential for chrysene. Chrysene has a "bay-region" in structure. It is metabolized by mixed function oxidases to reactive "bay-region" diol epoxides that are mutagenic in bacteria and tumorigenic in mouse skin painting assays and when injected into newborn mice.

GENERAL PROFILE

BIS(2-ETHYLHEXYU)PHTHALATE

Bis(2-ethylhexyl)phthalate otherwise known as DEHP (di(ethylhexyl)phthalate) is commercially produced by the reaction of two chemicals: 2-ethylhexyl alcohol and phthalic anhydride. It is used as a plasticizer for resins in the manufacture of organic pump fluids. DEHP is classified by the U.S. EPA as a probable human carcinogen. This classification is based on limited evidence from studies in humans and sufficient evidence that orally administered DEHP produced a significant dose-related increase in liver tumor responses in rats and mice of both sexes. DEHP can be inhaled, ingested, or irritate the skin and eyes. It effects the upper respiratory system and the stomach and intestines. It may irritate the eyes and mucous membranes and cause nausea and diarrhea.

GENERAL PROFILE

DI-N-OCTYL PHTHALATE

No information is available for di-n-octylph thai ate. As a group, the phthalic acid esters are oily liquids used as intermediates in manufacturing or as lubricants. They are generally toxic in high concentrations and some are considered to be carcinogenic.

GENERAL PROFILE

BENZOfBIFLUORANTHENE

Benzo (b) Fluoranthene B(b)F is one of the polycyclic aromatic hydrocarbon compounds. Because it is formed when gasoline, garbage, or any animal or plant material burns, it is usually found in smoke and soot. This chemical combines with dust particles in the air and is carried into water and soil and onto crops. B(b)F is found in the coal tar pitch used by industry, and is also found in creosote. People may be exposed to B(b)F from environmental sources such as air, water, and soil, and from cigarette smoke and overcooked food. Typically, exposures are not to B(b)F alone, but to a mixture of similar chemicals. The most common way B(b)F enters the body is through the lungs when a person breaths smoke or contaminated dust, or by eating contaminated or overcooked food. B(b)F does not normally enter the body through the skin, but if high concentrations are in the soil in areas near hazardous waste sites or if contact is made with used motor oil, small amounts of B(b)F could enter the body. B(b)F causes cancer in laboratory animals when applied directly to their skin. This finding suggests that it is likely that people exposed in the same manner could also develop cancer. Because studies with B(b)F are incomplete, it is not known if B(b)F inhaled or swallowed could cause cancer or any other harmful effect other than cancer.

GENERAL PROFILE

BENZOOOFLUORANTHENE

Benzo(k)fluoranthene is one of the polycyclic aromatic hydrocarbon (PAH) compounds. Because it is formed when gasoline, garbage, or any animal or plant material burns, it is usually found in smoke and soot. This chemical combines with dust particles in the air and is carried into water and onto soil and crops. Benzo(k)fluoranthene is found in coal tar pitch used by industry as an adhesive. People may be exposed to benzo(k)fluoranthene from environmental sources such as air, water, and soil, and from cigarette smoke and overcooked food. Typical exposures are not usually to benzo(k)fluoranthene alone, but to a mixture of similar chemicals. Current theories on mechanisms of metabolic activation of polycyclic aromatic hydrocarbons are consistent with carcinogenic potential for benzo(k)fluoranthene. Benzo(k)fluoranthene has a "bay-region" structure. It is metabolized by mixed function oxidases to reactive "bay-region" diol epoxides that are mutagenic in bacteria and tumorigenic in mouse skin painting assays.

GENERAL PROFILE

BENZO(A)PYRENE

Benzo(a)pyrene, (BAP), is a crystalline solid constituted in the class of polynuclear aromatic hydrocarbons (PAH). The U.S. EPA classifies this substance as a probable human carcinogen. It can be inhaled through vapors and particulates. It is also a common air contaminant of water, food, and smoke. No acute symptoms have been defined or documented. Chronic data provide information of BAP as a producer of genetic toxicological effects. Lung cancer has been shown to be induced in humans by various mixtures of PAH known to contain BAP, including cigarette smoke, roofing tar, and coke oven emissions. Skin cancers have also been noted. Multiple animal studies were conducted in rodent and nonrodent species demonstrating BAP to be carcinogenic following administration by oral, intratracheal, inhalation, and dermal routes. No quantitative data are available relating to oral or inhalation reference doses. For the Salem Acres site, the carcinogenic PAHs are:

• Benzo (A) Pyrene • Benzo (B) Fluoranthene • Benzo (K) Fluoranthene • Benzo (A) Anthracene • Chrysene • Indeno (l,2,3-c,d) Pyrene

GENERAL PROFILE

INDENOri.2.3-C.D)PYRENE

Indeno (l,2,3-c,d) pyrene is one of the polycyclic aromatic hydrocarbon (PAH) compounds. Because it is formed when fossil fuels, garbage, or any other plant or animal material is burned, it is usually found in smoke and soot. This chemical combines with dust particles in the air and is carried into water and onto soil and crops. Indeno(l,2,2-c,d)pyrene is found in coal tar pitch used by industry as an adhesive. There are animal data that specifically link exposure to indeno(l,2,3-c,d)pyrene with human cancers. It produced tumors in mice following lung implants, subcutaneous injection and dermal exposure. Indeno(l,2,3-c,d)pyrene is a component of mixtures that have been associated with human cancer. These include coal tar, soots, coke oven emissions, overcooked food and tobacco smoke.

GENERAL PROFILE

DIBENZCXA.HUNTHRECENE

Dibenz(a,h)anthracene is one of the polycyclic aromatic hydrocarbon (PAH) compounds. Because it is formed when fossil fuels, garbage, or any other plant or animal material is burned, it is usually found in smoke and soot. This chemical combines with dust particles in the air and is carried into water and onto soil and crops. Dibenz(a,h)anthracene is found in coal tar pitch used by industry as an adhesive. Although there are no human data that specifically link exposure to dibenz(a,h)anthracene with human cancers, it is a component of mixtures that have been associated with human cancer. These include coal tar, soots, coke oven emissions, overcooked food and tobacco smoke. Current theories on mechanisms of metabolic activation of polycyclic aromatic hydrocarbons are consistent with a carcinogenic potential for dibenz(a,h)anthracene. Dibenz(a,h)anthracene has a "bay-region" structure. It is metabolized by mixed-function oxidases to dihydrodiols that are mutagenic in bacteria and tumorigenic in mouse skin painting assays and when injected into newborn mice.

GENERAL PROFILE

BENZO(G.H.DPERYLENE

Benzo(g,h,i)perylene is one of the polycyclic aromatic hydrocarbon (PAH) compounds. Because it is formed when gasoline, garbage, or any animal or plant material burns, it is usually found in smoke and soot. This chemical combines with dust particles in the air and is carried into water and onto soil and crops. Benzo(g,h,i)perylene is found in coal tar pitch used by industry as an adhesive. People may be exposed to benzo(g,h,i)perylene from environmental sources such as air, water, and soil, and from cigarette smoke and overcooked food. Typical exposures are not usually to benzo(g,h,i)perylene alone, but to a mixture of similar chemicals.

GENERAL PROFILE

FURANS/DIQXINS

The chlorinated dibenzo-p-dioxins and dibenzofurans are a class of compounds that are loosely referred to as dioxins. There are 75 possible dioxins. The one with four chlorine atoms at positions 2,3, 7 and 8 of the dibenzo-p-dioxin chemical structure is called 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD). It is a colorless solid with no known odor. 2,3,7,8-TCDD does not occur naturally nor is it intentionally manufactured by any industry, except as a reference standard. It can be inadvertently produced in very small amounts as an impurity during the manufacture of certain herbicides and germicides and has been detected in products of incineration of municipal an industrial wastes. At the present time, 2, 3, 7, 8-TCDD is not used for any purpose other that scientific research. Dioxins and furans can affect human health by causing skin lesions, liver damage, digestive disorders, immune deficiency, reproductive failure, and low birth weight offspring. The human evidence for 2,3,7,8-TCDD alone is inadequate to demonstrate or reflect a carcinogenic hazard, although certain herbicide mixtures containing 2,3,7,8-TCDD as an impurity provide limited evidence of causing cancer in exposed humans. Based on the positive evidence in animal studies, 2,3,7,8-TCDD is probably carcinogenic in humans.

GENERAL PROFILE

ENDOSULFAN

Endosulfan is an organochlorine pesticide. It is toxic when inhaled and can be absorbed through the skin. Endosulfan is highly toxic to fish and other aquatic organisms. Occupational exposures have resulted in deaths due to improper safety practices. Its most potential effect is on the central nervous system.

GENERAL PROFILE

4.4'-DDE

4,4'-DDE, also classified as 1,1 Bis (4-chlorophenyl)-2-2-dichloroethane, is a crystalline solid. This compound forms from the environmental breakdown of DDT, an insecticide. The U.S. EPA classifies DDE as a probable human carcinogen. DDE is poisonous by ingestion. Poisoning may occur by ingestion or by absorption through the skin or respiratory tract. Acute symptoms include tumors of the head and neck muscles, toxic and chronic convulsions, and cardiac and respiratory failure leading to death. The estimated oral fatal dose is 500 mg/kg body weight of the solid material. Death occurs in two to 24 hours. Chronic effects include hepatic damage, CNS degeneration, agranulocytosis, dermatitis, weakness, convulsions, coma, and death.

GENERAL PROFILE

4.4' DDD

4,4' DDD is a colorless crystalline compound and is involved in the formulation and application of insecticides. The U.S. EPA canceled all pesticides using this product, and 4,4' DDD is no longer manufactured commercially. The EPA ranks DDE as a probable human carcinogen. 4,4' DDD is structurally similar to and is a known metabolite of DDT. There are sufficient animal studies and human studies supporting these data. There is some evidence that 4,4' DDD is cancerous, however, in other studies it does not appear cancerous, but is still mildly poisonous. 4,4' DDD has been shown to involve changes in chromosomes.

GENERAL PROFILE

4.4'-DDT

DDT, l,l,l-trichloro-2,2-J2is-(p-chlorophenyl)ethane, was one of the most widely used chemicals for controlling insect pests on agricultural crops and controlling insects that carry such diseases as malaria and typhus. Technical DDT is primarily a mixture of three forms (p,p'-DDT, o,p'-DDT, and o,o'-DDT), all of which are white, crystalline, tasteless, and almost odorless solids. In addition, DDE,1 ,l-dichloro-2,2-bjs(p-chlorophenyl)-ethylene,andDDD, 1, l-dichloro-2,2-bjs.(p-chlorophenyl)­ethane, are found in small amounts as contaminants in technical DDT. Humans can be exposed to DDT, DDE, and ODD primarily by eating food that contains small amounts of these compounds. Even though DDT has not been used in this country since 1972, small amounts of DDT and DDE are found in soil and, under certain conditions, may be transferred to crops grown on this soil. In addition, imported foods may have been directly exposed to DDT. The amount of DDT in crops has been decreasing and is expected to continue to decrease with time. In the United States, the DDT or its breakdown products are still found in air, water, and soil samples. Levels in most air and water samples are low, however, and exposure by these pathways is of little concern. Ingestion of DDT, DDE, and DDD, however, result in an increased occurrence of liver tumors. In the five studies of DDT exposed workers, results did not indicate increases in the number of deaths or cancers. EPA lists DDT, DDE, and DDD as probable human carcinogens.

GENERAL PROFILE

AROCLQR-1260. AROCLOR-1254 (PCBs)

Polychlorinated biphenyls (PCBs) are technical mixtures consisting of many compounds that vary from mobile oily liquids to solids and resins. Aroclor-1260, Aroclor-1254, and Aroclor-1242 are the PCBs found at the Salem Acres site. Health risk for all PCB mixtures are based on toxicity information for Aroclor 1260. PCBs are used in electrical capacitors, electrical transformers, vacuum pumps, and gas turbines. PCBs were formerly used in hydraulic fluids, plasticizers, adhesives and fire retardants. PCBs can be inhaled by vapors or fumes, absorbed through the skin, ingested, and contact and irritate the eyes and skin. Generally, toxic effects are dependent on the degree of exposure to chlorine particles, the higher the degree of exposure to chlorine particles, the stronger the effects. Acute and chronic exposure can cause liver damage. This substance is classified as a probable human carcinogen by EPA. There are two distinct effects on the body, namely a skin effect and a toxic action on the liver. Signs include swelling, discoloration of the skin, vomiting, anorexia, nausea, and fatigue. Where liver damage has been severe, the patient may pass into a coma and die.

GENERAL PROFILE

ALUMINUM

Aluminum is a light, silvery-white, soft, ductile, malleable metal. Routes of exposure are dermal and eye contact and inhalation. Health effects include necrosis of the cornea by particles deposited in the eye. Inhalation of aluminum powder is reported as a cause of pulmonary fibrosis. Salts of aluminum may cause dermatosis, eczema, conjunctivitis, and irritation of the mucous membranes of the upper respiratory system. Aluminum exposure has been implicated in Alzheimer's disease.

GENERAL PROFILE

ANTIMONY

Antimony is a silvery or gray lustrous metal widely used in the production of alloys, mining, smelting or refinery operations. Important alloys are pewter, babbitt, and white metal. Pure antimony compounds are used as abrasives, pigments, flame-proofing compounds, plasticizers, and explosives. Antimony and its compounds are generally regarded as primary skin irritants. They may attack the respiratory system, cardiovascular system, skin, eyes, and lungs. Symptoms of acute oral poisoning include violent irritation of the nose, mouth, stomach, and intestines; vomiting; bloody stools; pulmonary congestion, coma; and sometimes death due to circulatory or respiratory failure. Chronic poisoning presents symptoms of dry throat, nausea, headache, sleeplessness, loss of appetite, and dizziness. Liver and kidney changes are late manifestations.

GENERAL PROFILE

ARSENIC

Arsenic and its compounds are primarily used as insecticides, herbicides, and rodenticides. These substances are used in metallurgical processes for hardening copper, lead, alloys, and in the manufacture of certain types of glass. This substance and certain arsenic compounds have been listed as carcinogens by the U.S. EPA. Most forms of arsenic are toxic. Poisoning from arsenic compounds may be acute or long term. They are toxic either when inhaled or ingested. Acute symptoms following ingestion include irritation of the stomach lining, nausea, vomiting, and diarrhea, progressing to shock and death. Long-term poisoning can result in peeling and discoloration of the skin, herpes, inflammation of the nerves, altered formation and development of blood cells, and degeneration of the liver and kidneys. Chronic poisoning may manifest itself in different ways. Disturbances of the blood, kidneys, and nervous system are not infrequent. Arsenic can cause a variety of skin abnormalities, including itching and even cancerous changes.

GENERAL PROFILE

BARIUM AND COMPOUNDS

Elemental barium is a silvery-white metal generally found in nature as barium oxides in minerals. Numerous barium compounds are used for industrial purposes. The soluble barium salts, such as the chloride and sulfide, are poisonous when ingested. The usual result of exposure by inhalation or dermal contact is irritation of the eyes, nose, throat, and skin, producing dermatitis. Long term ingestion of small amounts of barium by rats can cause increased contractility of muscles. Heart rate is slowed. Other effects include intestinal, vascular, and bladder dysfunction due to increased muscle tension, and fetal toxicity.

GENERAL PROFILE

BERYLLIUM

Beryllium is a gray metal that is used extensively in the manufacture of electrical components, chemicals, ceramics and X-ray tubes. The metal is used to produce greater tensile strength, electrical conductivity, and resistance to corrosion and fatigue. Beryllium is also used as a neutron reflector in high-flex test reactors. This substance and certain beryllium compounds have been listed carcinogens by the U.S. EPA. Beryllium is inhaled as a fume or dust. These substances are highly toxic. Acute systemic effects primarily involve the respiratory tract and are manifested by a nonproductive cough, substernal pain, moderate shortness of breath, and some weight loss. Extent and severity of symptoms is dependent on type and extent of exposure. Severe chemical pneumonitis with pulmonary edema may result. Chronic beryllium disease is an intoxication arising from the inhalation of beryllium compounds. The chronic form of this disease is manifested primarily by respiratory symptoms, weakness, fatigue, and weight loss followed by a nonproductive cough and shortness of breath. Beryllium can attack the skin, eyes, respiratory system, lungs, liver, spleen, and heart (Sittig, 1985).

GENERAL PROFILE

CADMIUM

This metal produces byproducts consisting of various metal alloys. Cadmium is a high corrosion resistant metal and is alloyed with several other compounds. This substance and certain cadmium compounds have been listed as carcinogens. Exposure may occur through inhalation or ingestion of fumes or dust. It may attack the respiratory system, lungs, kidneys, prostrate and blood. Acute toxicity is almost always caused by inhalation of fumes or dust which are produced when cadmium is heated. Inhalation causes throat dry ness, coughs, headaches, vomiting, pneumonitis, and possibly bronchopneumonia. Ingestion may cause renal dysfunction, anemia, diarrhea, and tenesmus. Chronic cadmium poisoning has been reported after prolonged exposure to cadmium oxide fumes and cadmium oxide dust. Lung damage often results in the form of emphysema and risk of toxic effects including cancer.

GENERAL PROFILE

CALCIUM AND COMPOUNDS

Calcium is a soft silver-white metal. Calcium compounds have variable toxicity that can be poisonous by ingestion. Generally, calcium compounds should be considered toxic only when they contain toxic components, such as arsenic, or as calcium oxide or hydroxide. Routes of exposure include irritation of eyes, mucous membranes, and respiratory tract.

GENERAL PROFILE

CHROMIUM AND COMPOUNDS

Chromium may exist in one of three valence states in compounds, (II), (III), and (VI). Chromium metal (chromium (0)) is used in the steel making process and in electroplating. Chromic acid, along with chromates, is the hexavalent (VI) form and is found in compounds used for pigments, leather tanning, rubber making, wood treatment, and water treatment. Chromium (VI) is the most dangerous form of the element and is classified as a known human carcinogen. If inhaled as a dust it can cause lung cancer, and when injected into muscle tissue of rats it causes cancer at the site of injection. Non-cancerous effects of chromic acid and its salts include corrosive action on the skin and mucous membranes. The lesions are confined to the exposed parts, affecting chiefly the skin of the hands and forearms and the nasal septum. Acute exposures to dust or mist may cause coughing and wheezing, headache, dyspnea, pain or deep inspiration, fever, and loss of weight. Trivalent chromium (III) is an essential nutrient that must be included in the diet to maintain proper health. Direct contact with the skin can result in eczema (dermatitis), and over dosages taken orally can produce some of the same effects as hexavalent chrome (excluding cancer).

GENERAL PROFILE

COBALT AND COMPOUNDS

Cobalt is a silver-gray, hard, brittle metal. Some of the cobalt compounds are listed as hazardous by the EPA. Routes of entry are inhalation of dusts, ingestion, and dermal contact. Cobalt dust is mildly irritant to the eyes and to a lesser extent to the skin. It is an allergen and has caused allergic sensitivity type dermatitis in some industries where only minute quantities of cobalt are used. Inhalation of cobalt dust may cause an asthma-like disease with cough and dyspnea. This situation may progress to interstitial pneumonia with marked fibrosis. Pneumoconiosis may develop, which is believed to be reversible.

GENERAL PROFILE

COPPER

Copper is a reddish-brown metal used in the manufacture of bronzes, brass, electrical conductors, ammunition and works of art. Copper is toxic when inhaled as a fume or dust, ingested or when it contacts the skin and eyes. It can affect the lungs, skin, liver, and respiratory system. Copper salts can cause itching, and skin irritations. Copper salts can cause inflammation of the eyelids. Industrial exposure usually occurs from the fumes generated in welding copper-containing metals. Fumes and dust irritation cause breathing difficulties, nausea and in some instances discoloration of the skin and hair. Long-term affects rarely occur and then only in individuals with Wilson's disease. This is a disease which is caused when the body collects, stores, and retains large amounts of copper in the body. The disease is fatal if untreated.

GENERAL PROFILE

IRON AND COMPOUNDS

Iron is a malleable, silver-gray metal. Some forms of iron are slightly toxic in large quantities. Routes of exposure are inhalation of dust and dermal contact with compounds in solution. Harmful effects are associated with some iron compounds. The inhalation of iron oxide fumes or dust may cause a benign pneumoconiosis (siderosis). Iron compounds derive their dangerous properties from the radical with which the iron is associated. Iron pentacarbonyl is one of the more dangerous metal carbonyls. It is highly flammable and toxic. It can cause pneumonia, liver damage, vascular injury, and central nervous system degeneration.

GENERAL PROFILE

LEAD

Lead is an inorganic used for lining tanks, piping, and other equipment where pliability and corrosion resistance are required, such as in the chemical industry in handling corrosive gases and liquids used in the manufacture of sulfuric acid, petroleum refining, halogenation, sulfonation, extraction and condensation processes. It is also used as an ingredient in solder, a filter in the automotive industry, a shielding material for X-rays and atomic radiation, and in the manufacture of tetraethyl lead and inorganic and organic lead compounds, pigments for paint and varnishes, batteries, rubber, and plastics. It may also be added to bronze, brass, steel, and other alloys to improve their characteristics. The U.S. EPA classifies lead as a probable human carcinogen. Lead can be inhaled through common air contaminants, dust, fumes, mists and vapors; by ingestion of lead compounds trapped in the upper respiratory tract; or into the mouth via food, tobacco, and finger contact. Lead can also be absorbed through the skin. This route is of special importance in the case of organic compounds of lead, such as tetraethyl lead. Acute toxicity is most common in young children with a history of anorexia, vomiting, and malaise. Convulsions due to increased intracranial pressure may leave permanent brain damage. Chronic toxicity exhibits weight loss, weakness, and anemia. Lead poisoning in adults is usually occupational due mainly to inhalation of lead dust or fumes. More often there are stomach and central nervous system effects. Lead content of blood greater than 0.05 mg/1 and urine greater than 0.08 mg/1 support a diagnosis of lead poisoning.

GENERAL PROFILE

MAGNESIUM AND COMPOUNDS

Magnesium is a light silver-white metal. Routes of exposure are inhalation of dusts and ingestion of compounds. Magnesium and magnesium compounds are mild irritants to the conjunctiva and nasal mucosa, but are not specifically toxic. Magnesium salts, especially magnesium sulfate, have a laxative effect, particularly on new users, although the human body can adapt to the effects of magnesium with time.

GENERAL PROFILE

MANGANESE

Most of the manganese produced is used in the iron and steel industry in steel compounds. They are also utilized in the manufacture of dry cell batteries, paints, varnishes, inks, dyes, matches and fireworks, bleaching agent and as a coloring agent in the glass and ceramics industry. U.S. EPA has not classified manganese is relation to cancer in humans due to the lack of data in human and animal studies. Manganese can be inhaled as a dust or fume. Chronic manganese poisoning results from the inhalation of fumes or dusts. The central nervous system is the chief site of damage. It can also affect the lungs, blood, respiratory system, and kidneys. Early symptoms may include sleepiness, weakness of legs, mental confusion, and hallucinations. Speech disturbances, changes in skin texture and handwriting can be affected as the disease progresses. Chronic manganese poisoning is not a fatal disease although it is extremely disabling.

GENERAL PROFILE

MERCURY

Mercury, is a silver-white, heavy, mobile, liquid metal. It is used in barometers; thermometers; hydrometers; fluorescent lamps; extracting gold and silver from ores; making analgoms; in Pharmaceuticals; agricultural chemicals; and antifouling paints. Mercury can be inhaled, ingested, and may contact the eyes and skin. It can produce acute poisoning due to inhalation of mercury vapors. It affects the lungs primarily and can cause bronchitis, pneumonitis, and bronchiolitis. Chronic effects produce symptom complexes that can vary widely from individual to individual. These may include weakness, loss of appetite, loss of weight, insomnia, indigestion, diarrhea, increased salivation, soreness of mouth or throat, inflammation of the gums, loosening of the teeth, irritability, loss of memory, and tremors of fingers, eyelids, lips, or tongue. In general, chronic exposure produces four classical signs: gingivitis, sialorrhea, increased irritability, and muscular tremors. Rarely are all four seen together in an individual case (Sittig, 1985).

GENERAL PROFILE

NICKEL

Nickel is a hard magnetic metal with a silver-white color. It is used in electroplating, casting operations, for machine parts, in coinage; surgical and dental instruments; batteries, crank case oils; ceramics; glass; and synthetic coal oil production. The U.S. EPA classifies nickel as a human carcinogen. In industrial settings, nickel dust exposure caused lung and nasal tumors. Nickel is toxic when inhaled or ingested, and causes a reaction when it contacts the eyes and skin. The most common seen toxic reaction is reaction to the skin. This may cause dermatitis or chronic eczema. When swallowed, nickel effects cause nausea, vomiting, and diarrhea. This substance causes cancer in the lungs and nasal passages. Effects on the heart muscle, brain, liver, and kidney have been seen in animal studies.

GENERAL PROFILE

POTASSIUM AND COMPOUNDS

A soft, ductile, silvery white, reactive metal. The potassium cation is one of the major elements in the body. Toxicity of potassium compounds is almost always that of the anion. Contact with the metallic form of potassium can produce burns.

GENERAL PROFILE

SELENIUM AND COMPOUNDS

Selenium is found as a gray or red powder, or red crystals. Routes of exposure are inhalation of dusts, ingestion, and dermal absorption. Selenium is considered to be an essential nutrient, but has toxic effects at high exposure dosages. Elemental selenium is considered to be relatively nonirritating and is poorly absorbed. Some selenium compounds (particularly selenium dioxide and selenium oxychloride) are strong desiccants and can cause destruction of the skin. They are strong irritants to the upper respiratory tract and eyes, and may cause irritation of the mucous membrane of the stomach. Liver damage and other effects have been long recognized in livestock grazing on high selenium soil.

GENERAL PROFILE

SILVER

Silver is a white metal and combines with other elements to manufacture silverware, jewelry, coins, ornaments, plates, solders, in the application of metal films, on glass and ceramics, and paper. Some of the compounds are also of medical importance as antiseptics, astringents, and dental amalgams. Silver is toxic when inhaled as a fume or dust, ingested, or when it contacts the eyes and skin. It may cause permanent changes in skin color. The dust may irritate skin. Silver does not cause serious harmful effects, but prolonged absorption of silver compounds can lead to grayish-blue discoloration of skin. Once silver is deposited, there is no known method by which the silver can be removed.

GENERAL PROFILE

SODIUM AND COMPOUNDS

Sodium is a soft, ductile, malleable, silver white, reactive metal. Contact with the metallic form can produce burns, and in larger quantities, sodium poses a fire and explosion hazard. Toxicity of sodium compounds is almost always related to the anion. The Sodium cation is essential to life and is present in most living tissues.

GENERAL PROFILE

THALLIUM AND COMPOUNDS

A soft, heavy metal. Exposure is by inhalation or dermal contact with dusts and through skin absorption. Thallium is an extremely toxic and cumulative poison. In nonfatal occupational cases of moderate or long-term exposure, early symptoms usually include fatigue, limb pain, metallic taste in the mouth and loss of hair, although loss of hair is not always present as an early symptom. Later, peripheral neuritis, proteinuria, and joint pains occur. Occasionally, neurological signs are the presenting factor, especially in more severe poisonings. Long-term exposure may produce optic atrophy, paresthesia, and changes in pupillary and superficial tendon reflexes (slowed responses). Chronic exposure of .2 mg/kg/day in the diet causes changes in dermal enzymes and hair loss in rats.

GENERAL PROFILE

VANADIUM AND COMPOUNDS

Vanadium is a bright white soft ductile metal that is slightly radioactive. Vanadium compounds are respiratory irritants. More serious exposure may result in pulmonary edema and pneumonia, which may be fatal. Individuals who recover may experience persistent bronchitis resembling asthma, and bouts of dyspnea; however, no chronic lung lesions have been described. Chronic ingestion causes impaired kidney function.

GENERAL PROFILE

ZINC AND COMPOUNDS

Zinc is a bluish-white, lustrous metal. Pure zinc is an essential nutrient at low concentrations and is relatively non toxic at higher concentrations. Zinc compounds vary in toxicity, but are relatively non-toxic. However, zinc salts can be caustic. Chronic dosages taken orally result in anemia in humans.

GENERAL PROFILE

CYANIDES (TOTAL')

Cyanide (NOS) is commonly found in certain rat and pest poisons, silver and metal polishes, photographic solutions, and fumigant products. Cyanide is readily absorbed from all routes, including skin absorption, inhalation, and ingested through salts that are toxic. Death can occur within seconds of inhalation or ingestion. Death is due to respiratory arrest of central origin. Inhalation of toxic fumes represents a potentially rapid fatal type of exposure. Cyanide poisoning is reported to produce a bitter almond odor on the breath. Cyanide has a bitter, burning taste and following poisoning, symptoms of salivation, nausea without vomiting, anxiety, confusion, vertigo, giddiness, lower jaw stiffness, convulsions, opisthotonos, paralysis, coma, cardiac arrhythmias, and transient respiratory stimulation followed by respiratory failure may occur. Bradycardia is a common finding, but in most cases heartbeat usually outlasts respiration. Exposure to small amounts of cyanide compounds over long periods of time is reported to cause loss of appetite, headache, weakness, nausea, dizziness, and symptoms of irritation of the upper respiratory tract and eyes.

GENERAL PROFILE

TITANIUM

Titanium is a light weight metal used primarily by the aircraft industry. In foundries a dust is produced that is flammable. The naturally occurring state of titanium is as a mineral or salt. Titanium salts and titanium oxide are important ingredients in paint pigments. The salts are slightly poisonous if ingested. Inhalation of dusts containing titanium oxides produces irritating effects on mucous membranes and the lining of the lungs.

APPENDIX "B"

Technical Toxicity Profiles

TECHNICAL PROFILE

ACETONE

Classification

Acetone, C3H60, is a colorless liquid with a sweetish odor. It is used as a solvent for waxes, oils, resins, rubber, plastic, lacquers, varnishes, and rubber cement. It is classified as a noncarcinogen. This chemical has not been evaluated by the U.S. EPA for lifetime exposure for the potential as a human carcinogen.

Health Effects

Acetone may irritate the eyes, skin, nose, and throat. Its points of attack are the respiratory system and the skin. Inhalation may produce headache, fatigue, excitement, bronchial irritation, and in large amounts narcosis. Prolonged or repeated topical use may cause erythema and dryness.

Oral Exposure

The reference dose for chronic oral exposure has estimated values of 1 E-l mg/kg/day (U.S. EPA, 1986). A 90-day gavage study in albino rats was evaluated using acetone. Body weights, food consumption, clinical chemistry, hematology, and histo-pathologic parameters as well as organ weights and organ to body weight ratios were evaluated. Statistical analysis of the organ weight and ratio data revealed significant increased kidney weights for females in 500 and 2500 mg/kg group and increased kidney to body and brain weight ratios for males and females in the 2500 mg/kg group. Liver weight and liver/body weight ratios were also increased in the 2500 mg/kg males and females. Histopathologic studies revealed a marked increase in severity in tubular degeneration of the kidney and hyaline droplet accumulation with increasing doses. Animal NOAEL of 100 mg/kg/day and a LOAEL of 500 mg/kg/day were established. Limited human studies have shown that workers exposed to acetone vapors (600 to 2150 ppm) experienced transient eye and nose irritation. Animals exposed to acetone vapors at 45,134 mg/m1 experienced slight decreases in organ and body weights. The confidence in the oral reference dose was rated medium due to limited number of studies conducted.

Inhalation Exposure

The reference dose for chronic inhalation exposure is 3 E+l (IRIS, 1990).

Toxicity to Human Health and Animals

No ambient water quality values have been established for aquatic organisms to date (IRIS, 1990).

TECHNICAL PROFILE

BENZENE

Classification

The hydrocarbon benzene, CSHS, is a clear, volatile colorless liquid with a characteristic odor. This aromatic compound is recognized as a human carcinogen (IARC, 1982; IRIS, 1989). The International Agency for Research on Cancer (IARC) weight of evidence category for carcinogenicity is establishing sufficient evidence from epidemological studies to support a casual association between benzene and cancer in humans (ICF, 1985).

Health Effects

Poisoning occurs most commonly via inhalation of the vapor, though benzene can be ingested and penetrate the skin and poison in that manner.

Oral Exposure

Several epidemiological studies provide sufficient evidence of a causal relationship between benzene exposure and leukemia in humans (IARC, 1982). Benzene is a known inducer of aplastic anemia in humans, with a latent period of up to 10 years. It produces leukopenia and thrombocytopenia, which may progress to pancytopenia. Similar adverse effects on the blood-cell producing system occur in animals exposed to benzene. In both humans and animals benzene exposure is associated with chromosomal damage, although it is not mutagenic in microorganisms (IARC, 1982). Benzene was fetotoxic and caused embryolethality in experimental animals.

Numerous investigations have found significant increases in chromosomal aberrations of bone-marrow cells and peripheral lymphocytes from workers with exposure to benzene (IARC, 1982). Locally, benzene has a strong irritating effect producing erythema and burning and in more severe cases edema and blistering. Benzene is a recognized leukemogen. There is no specific blood picture occurring in cases of chronic benzol poisoning. The bone marrow may be hypoplastic, normal, or hyperplastic. Anemia, leucopenia, macrocytosis, reticulocytosis, thrombocytopenia, high color index, and prolonged bleeding may be present.

Benzene is an experimental mutagen, carcinogen, and teratogen. Quantitative estimates of carcinogenic risks from oral exposure are estimated as 2.9 E-2 mg/kg/day and drinking water risk estimate at 8.3 E-7/jag/l .The human

respiratory rate was assumed to be 20mVday, inhalation absorption was taken as 100%, and an air concentration of benzene of 1 ppm was taken to equal 3.25 mg/m3 (IRIS, 1987). The water unit risk was calculated on the estimated human consumption of two liters of water per day.

Inhalation Exposure

Benzene is a common air contaminant. Exposure to high concentrations of benzene about 20,000 ppm (66,000 mg/mj) in air can be fatal within minutes (IARC, 1982). The prominent signs are central nervous depression and convulsions, with death usually following as a consequence of cardiovascular collapse. Milder exposures can produce vertigo, drowsiness, headache, nausea, and eventually unconsciousness if exposure continues. Deaths from cardiac sensitization and cardiac arrhythmias have also been reported after exposure to unknown concentrations. Although most benzene hazards are associated with inhalation exposure, dermal absorption of liquid benzene may occur and prolonged or repeated skin contact may produce blistering, erythema, and a dry, scaly dermatitis.

Quantitative estimates from inhalation exposure have an estimated inhalation slope factor of 2.9 E-2 mg/kg/day"l

and an inhalation unit risk of 8.3 E-6 vig/m3 . Air concentration levels do not exceed 1E+1 ug/m1 for 1 in 10,000 persons (IRIS, 1987).

Toxicity to Human Health and Animals

Benzene has been listed as a hazardous air pollutant under Section 112 of the Clean Air Act. EPA established maximum contaminant level goal (MCLG) for drinking water at 0 mg/1 based on its carcinogenic effects and a maximum contaminant level (MCL) of 5 jag/1 for drinking water.

The ambient water quality criteria (AWQC) for human health established a level of 6.6 E-l mg/1 and 4.0 E+l mg/1 for water and fish consumption, respectively. For maximum protection from the potential carcinogenic properties, the AWQC should be zero. However, zero may not be attainable at this time so the recommended criteria represents an increase of risk over a lifetime.

The AWQC for freshwater organisms are measured at 5.3 E+3 Vtg/1 and 5.1+3 ng/1 for marine organisms. Chronic values are only recognized for marine species as 700 Vig/liter (IRIS, 1987). Results based on unmeasured concentrations in static tests are likely to underestimate toxicity for relatively volatile compounds like benzene. A chronic list with Daphina magna was incomplete, with no adverse

effects observed at test concentrations as high as 98,000 mg/1.

For saltwater species, acute toxicity values for one fish and five invertebrate species range from 10,900 |ag/l to 928,000 ng/1. Freshwater and saltwater plant species that have been studied exhibit toxic effects at benzene concentrations ranging from 20,000 jag/l to 525,000 iag/1 (Sittig, 1983).

TECHNICAL PROFILE

2-BUTANONE

2-Butanone, otherwise known as Methyl ethyl ketone (MEK), C4H8O, is a colorless liquid used as a solvent in coating industries, manufacturing of synthetic resins, in cements and adhesives, and in the dewaxing of lubricating oils .

Classification

The weight of evidence classification by the U.S. EPA categorizes MEK in Group D, which does not list MEK as a human carcinogen. No data presently exist to evaluate this classification, and evidence for carcinogenicity in humans and animals was inadequate.

Health Effects

MEK may affect the central nervous system and the lungs. It may be inhaled, absorbed through the skin, ingested, or contact the eyes and skin. Headaches, dizziness, or vomiting may develop. It is moderately toxic by ingest ion. MEK irritates the eyes at concentration in the range of 350 ppm. No other adverse effects have been observed.

Oral Exposure

The oral reference dose is calculated to be 5E-1 mg/kg/day. No quantitative estimate for carcinogenic risk from oral exposure is available. No human carcinogenic data are available. In a skin carcinogenesis study, no skin tumors developed in mice treated with 25 percent MEK. One of the 10 mice receiving 29 percent MEK developed a skin tumor. MEK was not mutagenic for Salmonella typhimurium strains TA98, TA100, TA1535, or TA1537 with or without rat hepatic homogenates (Florin, 1980). MEK induced aneuploidy in the diploid D61, M strain of Saccharomyces cerevisiae (Zimmerman, 1985). Low levels of MEK combined with low levels of nocodazole also produced elevated levels of aneuploidy in the system (Mayer and Gain, 1987).

Inhalation Exposure

The reference dose for chronic inhalation exposure is 9E-1 mg/kg/day. No data were available to assess carcinogenic potential of MEK by oral or inhalation routes,

Toxicity to Human Health and Animals

No criteria have been set as permissible concentrations in water for human health and aquatic organisms.

TECHNICAL PROFILE

CARBON DISULFIDE

Classification

Carbon disulfide, CS2, is a mobile, clear, or faintly yellow liquid. Pure distillates have a sweet pleasing ethereal odor. Reagent and commercial grades are foul-smelling. It is used in the manufacture of soil disinfectants, vacuum tubes, and for cleaning and extractions, especially in metal treatment and plating. It is a fumigant for commodities, a corrosion inhibitor, and a polymerization inhibitor for vinyl chlorides. This chemical has not been evaluated by the U.S. EPA for evidence of human carcinogenic potential. No weight of evidence is classified.

Health Effects

Poisoning usually occurs from inhalation but also may be caused by ingestion and skin absorption. Acute toxicity exhibits euphoria, restlessness, mucous membrane irritations, nausea vomiting, unconsciousness, and terminal convulsions. Chronic toxicity exhibits marked psychic disturbances ranging from extreme irritability to mania with hallucinations, tremors, auditory and visual disturbances, weight loss, and blood dyscrasis. Dermal contact with concentrated solutions may cause burning pain, erythema, and exfoliation.

Oral Exposure

An estimate of 7.3 ppm of CSZ can be considered as a NOAEL for neurotoxicity. This dose, when extrapolated to an oral reference dose of 1E-1 mg/kg/day, lends support to the animal NOAEL of 11 mg/kg/day. Hardin et al. (1981) observed no effects on fetal development in rats and rabbits following inhalation exposures which correspond to an oral dosage of 10 mg/kg for rats and 22 mg/kg for rabbits. The highest NOAEL of 22 mg/kg for the rabbit should not be used for a reference dose estimate because adverse effects were seen in rabbit fetuses following oral exposure of pregnant doses to 25 mg/kg (Price et al., 1984). The highest NOAEL that is below an effect level is the estimated low dose from the Hardin (1981) inhalation study using rabbits. This dose level is the most appropriate basis for reference dose. An oral study (Price et al., 1984) observed 25 mg/kg/day in rabbits as an PEL. Fetotoxicity and fetal malformations were not observed with lowest CS2 exposure. Rabbit fetus was observed to be more sensitive than the rat fetus to carbon disulfide-induced toxicity. Significant alterations in

sensory conduction velocity and peroneal motor conduction velocity and minimal neurotoxicity was evident in clinical findings. Reduction of nerve conduction velocity was in normal range values and not associated with specific health consequences. Fetal malformations in rats were observed, and relates the reference dose level to be lower than the reference dose that is derived from existing guidelines and epidemiologic data (Tabatcova et al.). The confidence in the oral reference dose is medium based on the need for additional chronic toxicity studies.

Inhalation Exposure

No reference dose for chronic inhalation exists (IRIS, 1990). The federal standard has been established at 60 mg/m3 determined as an eight-hour time weighted average (TWA). NIOSH recommends that TWA concentration be limited to 3 mg/m3 (Sittig, 1981).

Toxicity to Human Health and Animals

No ambient water quality criteria have been established for aquatic organisms to date. In view of the paucity of data on the mutagenicity, carcinogenicity, and long-term oral toxicity, estimates of chronic oral exposure for human health and for aquatic organisms cannot be made with any confidence.

TECHNICAL PROFILE

CHLQROBENZENE

Chlorobenzene C6HSC1, otherwise known as benzene chloride, is a clear, colorless liquid used in the manufacture of aniline, phenols, and as an intermediate of dyes and pesticides.

Classification

The weight of evidence for carcinogenicity by the U.S. EPA is presently being evaluated. This does not imply that Chlorobenzene is necessarily a carcinogen.

Health Effects

Chlorobenzene can be inhaled, ingested, or irritate the eyes and skin. It may affect the respiratory and central nervous systems, and the liver. It may cause drowsiness, incoherence, skin irritation, and liver damage. Little is known of the effects of repeated exposures at lower concentrations, but it may also cause kidney damage. Histopathologic changes have been observed in the liver in animal studies (Monsanto, 1967).

Oral Exposure

Cytologic alterations and leukocytic infiltration of the stroma (all in liver) were observed in dogs given Chlorobenzene orally (Monsanto, 1967). Death, body weight loss, various changes in hematology, clinical chemistry, urine analysis, and pathologic changes in liver, cytologic changes, leukocytic infiltration, centrolobular degeneration, kidney, gastrointestinal mucosa, and hematopoietic tissue at 272.5 mg/kg/day were observed for oral toxicity (Knapp, 1971). Subchronic studies were given medium confidence because they need a more complete toxicity assessment. The oral Rfd is 3E-2 mg/kg/day.

Inhalation Exposure

The reference dose for chronic inhalation exposure is 5E-3 mg/kg/day.

Toxicity to Human Health and Animals

No ambient water quality criteria (AWQC) exist for human health and aquatic organisms. A level of 250 yg/1 was established on an acute basis. To protect saltwater aquatic life, 160 ng/1 on an acute basis and 129 ug/1 on a chronic basis for chlorinated benzenes as a class (Sittig, 1983) were established.

TECHNICAL PROFILE

TRANS-1,2-DICHLQROETHENE

Trans-1,2,-dichloroethene is an ethereal liquid with an acrid odor. It gradually decomposes in air in the presence of light and moisture releasing HC1 as a by-product. It is used as a solvent for fats, phenol, camphor, etc. Inhalation of vapors causes respiratory irritation and narcosis.

Classification

The USEPA weight of evidence is a classification of a chemicals likelihood for carcinogenicity. Trans-1,2-dichloroethene has not been evaluated by the U.S. EPA for evidence of human carcinogenic potential.

Health Effect

Male and female mice were given trans-1,2-dichloroethene (DCE) in their drinking water. There were no differences in fluid consumption among the various groups of mice and at the termination of the 90- day experiment, no DCE-induced changes in terminal body weight or gross pathology were noted in either sex at any dose level. In male mice, there were significant increases in serum enzyme levels. In addition, liver glutathione concentrations were decreased at the highest dose. In females, the thymus weight, calculated as percent body weight, was significantly decreased, while the lung weight was depressed at the highest dose only. The levels of serum enzymes were decreased at the higher doses. Since there is uncertainty about the toxicological significance of the decreases in serum enzymes, these parameters were not used by EPA to set RfD values.

The immunotoxicity of trans-1,2-dichloroethene was assessed. In males on day 4 after treatment, there was a significant decrease, but the decreases were only significant at high levels when the data were calculated on the basis of spleen cells. No dose-dependent effects were noted in the DCE-treated female mice. The significance of the decrease in AFC/spleen in male mice at all three dose levels is uncertain.

Oral Exposure

Rats, 22 to 30 days old, were given trans-1,2-dichloroethene for 90 days in their drinking water The authors found no compound-related effects on fluid consumption, body weights, hematology, serum chemistry or urinalyses. They did note a significant dose-dependent decrease in kidney weight in female rats .

Inhalation Exposure

Wistar rats were exposed to air containing trans-l,2-dichloroethene. Brief (8-hour) or prolonged (8 hours/day, 5 days/week for 1, 2, 8, or 16 weeks) exposure at 200 ppm produced slight degeneration of the liver lobule and lipid accumulation in the Kupffer cells. At 8 and 16 weeks of exposure, severe pneumonic infiltration was observed. Exposure at 1000 ppm for 8 hours resulted in significant reductions in serum albumin, urea nitrogen and alkaline phosphatase. Eight-hour exposures at both 200 and 1000 ppm produced a significant decrease in the number of leucocytes.

Toxicity to Human Health and Animals

Not available at this time.

TECHNICAL PROFILE

ETHYLBENZENE

Ethylbenzene, CaHi0, is a colorless liquid with a pungent aromatic odor. It is used in the manufacture of cellulose acetate, styrene, and synthetic rubber.

Classification

The U.S. EPA weight of evidence classification is Group D: not a human carcinogen based on the lack of animal bioassays and human studies.

Health Effect

Ethylbenzene is moderately toxic by irritation to skin, eyes, mucous membranes, and by ingestion and inhalation routes (Sax/Lewis, 1987). The liquid is an irritant to the skin and mucous membranes. A concentration of 0.1 percent of vapor in the air is an irritant to human eyes, and a concentration of 0.2 percent is extremely irritating at first, then causes dizziness, irritation of the nose and throat, and a sense of constriction in the chest. Exposure of 1 percent concentration has been reported as causing atoxia, loss of consciousness, tremor of the extremities, and finally death through respiratory failure. Pathological findings were congestion of the brain and lungs, with edema. Ethylbenzene is an experimental teratogen.

Oral Exposure

A reference dose for chronic oral exposure calculates the NOAEL as 97.1 mg/kg/day and a LOAEL limit of 291 mg/kg/day. The LOAEL is associated with the histopathologic changes in the liver and kidney (Wolf, 1956). Toxic effects on the test animals were growth, mortality, appearance and behavior, hematologic findings, terminal concentration of urea nitrogen in the blood, final average organ and body weights, histopathologic findings, and bone marrow counts. The confidence of the oral reference dose is low due to limited duration and sex examined.

No human carcinogenic data are available (IRIS, 1990). The National Toxicology Program (NTP) plans to initiate bioassays in animal studies. Metabolism and excretion studies varying dose levels are to be conducted.

No quantitative estimate has been established in relation to carcinogenic risks from oral exposure.

Metabolic pathways for humans and rodents were noted to be different (Engstrom, 1984). Major metabolites in humans, mandelic acid and phenyl glyoxylic acid, are minor metabolites in rats and rabbits (Kiese and Lenk, 1974). Ethylbenzene was not mutagenic for Salmonella strains TA98, TA1535, TA1537, and TA1538 with or without Aroclor 1254 induced rat liver homogenates (S9) (Nestmann, 1980). Ethylbenzene was shown to increase the number of sister chromatid exchanges in human whole blood lymphocyte culture at the highest dose examined, without any metabolic activation system (Norppe and Vainio, 1983).

Ethylbenzene was not mutagenic in the range of concentrations tested for S. typhemurium TA98, TA100, TA1535, TA1537, and TA1538 or for Escherichia coli WP2 and WP2 uvrA (Dean et al., 1985).

Inhalation Exposure

Human volunteers exposed to ethylbenzene by inhalation at a concentration of 100 ppm established exposure conditions, and assumed an absorption factor of 64 percent to be equivalent to a NOAEL of 31.8 mg/kg/day.

A one day health advisory, assumary, 1 liter per day for a 10 kg child, is 3.2E+1 mg/1. Appropriate inhalation data for a long-term health advisory are not available.

Toxicity to Human Health and Animals

The DWEL is 3.4E+0 mg/1. Organoleptic properties established taste and odor thresholds for water to be .029 mg/1. Odor perception threshold is .062 mg/1.

The maximum contaminated level goal (MCLG) is 0.68 mg/1 for drinking water. A MCLG of 0.68 mg/1 for ethylbenzene is proposed based on the provisional DWEL of 3.4 mg/1 and an assumed drinking water contribution of 20 percent. To protect human health, a level of 1.4 mg/1 is established for water and fish consumption. To protect freshwater and marine aquatic life, acute toxicity levels are calculated to be 32,000 ]ug/l and 430 |ag/l, respectively. An Rfd for oral exposure has been established at 1.1E-1 mg/kg/day,

TECHNICAL PROFILE

METHYLENE CHLORIDE

Methylene chloride, is a nonflammable, colorless liquid with a pleasant aromatic odor. It is used as a solvent for degreasing and cleaning fluids and as a solvent for food processing.

Classification

The weight of evidence classification given to dichloromethane is B2, recognizing this substance as a probable human carcinogen. Human carcinogenicity data are inadequate. Neither of the two studies of chemical factory workers showed an excess of cancers (Frielandie, 1978). Exposures were low in former studies but the data provides some suggestion of increased incidence of pancreatic tumors. The latter report was designed to examine cardiovascular effects, and the study was too short to allow for latency of site-specific cancers.

Health Effects

Dichloromethane can irritate the eyes, nose, and throat. It can be inhaled as a vapor, absorbed-through the skin, or ingested. Methylene chloride is a mild narcotic. Effects from intoxication include headache, giddiness, stupor, irritability, numbness, and tingling in the limbs. Irritation to the eyes and upper respiratory passages occurs at higher dosages. In severe cases, observers have noted toxic encephalopathy with hallucinations, pulmonary edema, coma, and death. Cardiac arrythmias has been produced in animals but have not been common in human experience. Exposure to this agent may cause elevated carboxy hemoglobin levels which may be significant in smokers, workers with anemia or heart disease, and those exposed to carbon monoxide.

Oral Exposure

The oral Rfd is 6E-2 mg/kg/day. Supporting studies related histological alterations of the liver at nominal doses of 50 mg/kg/day (National Coffee Assoc. 1982) or higher. Supporting data are limited. An NOAEL of 87 mg/mj was reported in one inhalation study (Houn et al., 1972). Confidence in the oral reference dose was high due to a large number of animals of both sexes used. Many effects were monitored and dose-related increases observed. Dichloromethane is mutagenic for Salmonella typhimurium with or without added hepatic enzymes (Green, 1983) and produced mitotic recombination in yeast

(Collen, 1980). Results in cultured mammalion cells have been negative, but dichloromethane has been shown to transfer rat embryo cells and to enhance viral transformation of Syrian hamster embryo cells (Price et al., 1978). The oral slope factor estimates are calculated to be 7.5 E-3 mg/kg/day"l with a drinking water unit risk factor of 2.1 E-7 |ag/l.

Inhalation Exposure

Inhalation exposure of male and female Syrian hamsters (NCA, 1983) did not produce neoplasia. Female Sprague -Dawley rats reduced survival at the highest dose. Increased incidences of mammary tumors were noted in both females and males. Male rats developed salivary gland sarcomas (Burek et al., 1984). The quantitative estimate of carcinogenic risk from inhalation exposure is 1.4 E-2 mg/kg/day and established an inhalation unit risk of 4.l E-6 ug/m3.

Dichloromethane was considered to be a well-absorbed vapor at low doses. As of December 1987, a revision of the cancer risk assessment is pending final approval. This revision contains a new inhalation potency on the incorporation of information on pharmokinetics and metabolism. An adequate number of animals was observed and tumor incidences were increased in a dose-dependent fashion. Analysis excluding animals which died before observation of the first tumors produced similar risk estimates as did time to tumor analysis (NTP, 1986).

Toxicity to Animals

Ambient water quality criteria (AWQC) for human health and aquatic organisms were established based under the threshold value as dichloromethane as a carcinogen. Since methylene chloride is classified as a carcinogen, the recommended AWQC is zero. If zero cannot be obtained and exposure is via ingestion of water and aquatic organisms, 0.19 )jg/l is associated with an upper-bound excess lifetime risk of 1.0 E-6. If exposure is only via ingestion of aquatic organisms, the AWQC associated with an upper bound excess lifetime risk of 1 E-6 is 15.7 iug/l. Water and fish consumption is calculated to be 1.9E |ag/l for human health. Likewise a value of 1.57 E+l )ag/l is given to fish consumption.

Acute toxicity values for freshwater and marine organisms are l.l E+4 pg/1 and 1.2 E+4 pg/1, respectively. No chronic value is calculated for freshwater organisms. A value of 6.4 E+3 ng/1 is the value associated with the chronic toxicity level for marine organisms.

TECHNICAL PROFILE

TOLUENE

Toluene, C7H8, is commonly known as methylbenzene. It is a colorless liquid derived from coal tar. Toluene is used in the manufacture of benzene, as chemical feed, and as a solvent for paints and coatings.

Classification

The U.S. EPA's weight of evidence classification as to human carcinogenicity is Group D: not classified as a carcinogen based on no human data and inadequate animal data. Toluene did not produce positive results in the majority of genotoxic assays.

Health Effects

Toluene is a poison by intraperitoneal routes. It is moderately toxic by inhalation and subcutaneous routes. Mutagenic data exist. It is known to be a skin and eye irritant. Toluene affects the central nervous system, the liver, and skin. Inhalation of 200 ppm of toluene for eight hours may cause impairment of coordination. With higher concentrations, these effects are increased. Acute exposure to toluene includes symptoms of headache, dizziness, fatigue, drowsiness, and lack of coordination. Chronic effects report anemia and leukopenia, with biopsies showing bone marrow hypoplasia.

Oral Exposure

Toluene is most likely a potential source of respiratory hazards. A chronic inhalation toxicology study in Fisher 344 rats (CITT, 1980) noted all normal parameters, except for dose-related reduction in hematocrit values if females were exposed to ranges of toluene concentrations. An oral reference dose of 1.OE 0 mg/kg/day was derived using route-to-route extrapolation. Subchronic oral studies support the chosen no observed adverse effect level (NOAEL) of 300 ppm or 1,120 mg/m3 (NTP, 1981, 1982). An oral study containing subchronic data observed no adverse effects of toluene at the highest dose tested (590 mg/kg/day) (Wolf, 1956).

A chronic bioassay of toluene reported no carcinogenic responses. No increases were reported in neoplastic tissue or tumor masses among treated rats (CUT) . Derminal applications and examination of the carcinogenicity applied to interscapular skin of 54 male

mice produced no carcinogenic response (Poil, 1963). No increase in the incidence of skin or systemic tumors was demonstrated (Lijinsky and Garcia, 1972).

Toluene was not found to be mutagenic in reverse mutation assays with S. typhimurium (Mortelmans and Riccio, 1980) and E. coli (Mortelmans and Ricciro, 1980) with and without metabolic activation. Toluene did not induce mitotic gene conversion or mitotic crossing over Toluene did not cause increased chromosomal aberrations in bone marrow cells. Several studies (Dobrokhotov, 1972) reported toluene as effective in causing chromosomal damage in bone marrow cells of rats, however, there was no evidence of chromosomal aberrations in blood lymphocytes (Maki-Paakkanen, 1980).

Inhalation Exposure

Quantitative estimates from inhalation exposure produces a RfD of 3E-1 mg/kg/day (IRIS, 1990).

Toxicity to Human Health and Animals

A maximum contaminant level goal (MCLG) proposed in 1985 is 2.0 mg/1 for drinking water. This is based on a drinking water equivalent level (DWEL) of 10.1 mg/1 and an assumed contribution of 20% from drinking water. The ambient water quality criterion for human health is 14.3 mg/1 based on the consumption of contaminated aquatic organisms and water. A water quality level (WQL) of 424 mg/1 has also been established based on consumption of contaminated aquatic organisms alone.

The ambient water quality criterion for freshwater organisms is 17,500 ng/1 for acute toxicity. Marine organisms have acute and chronic toxicity levels of 6,300 jjig/1 and 5,000 pg/1, respectively.

TECHNICAL PROFILE

TETRACHLOROETHENE

Tetrachloroethene is a commercially important chlorinated hydrocarbon solvent and chemical intermediate. It has been widely used as a dry-cleaning and textile-processing solvent and for vapor degreasing in metal-cleaning operations. Currently, four U.S. manufacturers (operating six production facilities) produce about 0.5 billion pounds of tetrachloroethene annually. Imported quantities of tetrachloroethene are significantly larger than exported quantities.

Tetrachloroethene is readily absorbed following inhalation exposure. Absorption of tetrachloroethene following ingestion is also rapid and nearly complete. Peak blood levels of tetrachloroethene are reached within one hour following oral administration of the compound in both humans and animals. In contrast to the extensive absorption of tetrachloroethene following inhalation or oral exposure, absorption of the chemical following dermal exposure is poor.

Limited acute toxicity data indicate that tetrachloroethene is relatively nontoxic by the inhalation and oral routes. A four hour LC50 of 5,200 ppm for mice and a single-dose LDSO of 3,005 mg/kg for rats have been reported. Ingestion of approximately 60 to 86 mg of tetrachloroethene per kg of body weight by humans for antihelminthic medication was reported to be nonlethal.

The principal target organs of tetrachloroethene toxicity are the CNS, liver, and kidneys. Interpretation of the available data is complicated by differences in species, exposure schedules, and end points, but the CNS and liver appear to be the most sensitive targets. Continuous-inhalation exposure for 30 days induced hepatic effects in mice at concentrations as low as 9 ppm; CNS effects in gerbilo occurred at concentrations as low as 60 ppm, when exposed for 3 to 12 months. Short-term inhalation studies indicate that the threshold for CNS effects in humans is in the range aof 100 to 200 ppm. The chronic RfD (oral) is 1x10"2 mg/kg/day.

Limited oral toxicity data are available, but subchronic exposure to doses >100 mg/kg/day produced hepatic effects in mice and rats.

Fetotoxic effects, including skeletal ossification anomalies, occurred in mice and rats exposed to >300 ppm tetrachloroethene by inhalation, but teratogenic effects were not observed. Subtle effects on behavioral

performance and brain neurochemistry in the offspring of mice were associated with gestational exposure to 900 ppm. Oral teratogenicity data are not available.

There is little information concerning reproductive effects of tetrachloroethene. A short-term inhalation study suggests that tetrachloroethene may cause sperm abnormalities in mice but not rats.

Some epidemiological studies suggest a possible association between chronic tetrachloroethene exposure and increased cancer risk, but confounding factors (particularly exposure to other chemicals) and study limitations make the association inconclusive. Chronic inhalation exposure to tetrachloroethene produced increased incidences of mononuclear cell leukemia in rats, kidney tumors in male rats only, and hepatocellular adenomas and carcinomas in mice. Although the increased incidence in kidney tumors in male rats was not statistically significant, this type of tumor is considered rare. Chronic oral exposure to tetrachloroethene produced increased incidences of hepatocellular carcinomas in mice. The EPA weight of evidence is B2. A primary metabolite of tetrachloroethene, trichloroacetic acid, and a minor metabolite, dichloroacetic acid, have been shown to induce liver cancer.

TECHNICAL PROFILE

1,1,1-TRICHLQROETHANE

Classification

1,1,1-Trichloroethane (1,1,1-TCE), C2H3Clj, is a colorless liquid that has a pleasant odor and is an isomer of 1,1,1-trichloroethane. 1,1,1-TCE is comparable to carbon tetrachloride and tetrachlorethane in toxicity. Weight of evidence classification by the U.S. EPA as to human carcinogenicity is categorized under Group C as being a possible human carcinogen. Limited evidence of carcinogenicity in animals is available. No human toxic effects have been reported.

Health Effects

1,1,1-TCE is poisonous by intravenous and subcutaneous routes. It is moderately toxic by ingestion, inhalation, skin contact, and intraperitoneal routes. This substance severely irritates the eyes and has narcotic properties. It may be injurious to the liver and kidneys. 1,1,1-TCE is an experimental carcinogen, and mutagenic data exist. Animal experiments show 1,1,1-TCE to be a potential nervous system depressant. The injection of anesthetic doses in animals was associated with both kidney and renal neurosis.

Oral Exposure

Studies by White et al. (1985) and Sanders et al. (1985) derived an oral reference dose of 9 E-2 mg/kg/day. Clinical chemistry indicated adverse effects on the liver in both sexes. Effects on the erythrocytes occurred only in female mice and depressed humoral immune status occurred in both sexes at 200 and 2000 mg/1. A medium confidence level of the oral reference dose is given due to balanced strengths (clinical chemistries) and weaknesses (lack of histopathology and a NOAEL).

No human carcinogenicity data are available from two statistical lists (NCI, 1978). Treatment of mice was found to be associated with increased incidence of hepatocellular carcinomas. A dose-related increase in pheochromocytomas was confirmed in female mice. Tumors found in treated but not controlled rats included adrenal cortical carcinomas, transitional-cell carcinomas of kidney, renal tubular adenomas, hemangiosarcomas of spleen, pancreas, abdomen, and subcutaneous tissue.

1,1,1-TCE was found to be a nonmutagenic for Salmonella typhimurium (Simmon et al., 1977). Inhaled 1,1,1-TCE was identified among the urinary metabolites (Yllnu, 1971; Skeda and Ohtseyi, 1972). Dose-related increases in hepatocellar carcinomas were observed in adequate numbers of mice in both sexes. Background incidence of this tumor is high.

Inhalation Exposure

The reference dose for chronic inhalation exposure is 5 E-2 mg/kg/day (IRIS, 1990).

Toxicity to Human Health and Animals

No hazardous assessment for varied exposure durations is available at this time. The ambient water quality criteria (AWQC) have established levels for protection of human health. Water and fish consumption is estimated to be 6.0 E-l ng/1. A value of 4.18 E+' jag/1 is associated for fish consumption only. For the maximum protection from the potential carcinogenic properties of the chemical, the ambient water concentration should be zero. Zero may not be attainable at this time, so the recommended criteria represent a E-6 estimated incremental increase of cancer risk over a lifetime.

The AWQC established for aquatic organisms have established values of 1.8 E+4 iag/1 and 9.4 E+3 ng/1 as the acute and chronic toxicity effect levels for freshwater organisms. No values have been estimated for marine organisms.

TECHNICAL PROFILE

TRICHLOROETHENE

Trichloroethene C2HC13, a nonflammable mobile liquid, has a characteristic odor resembling chloroform. It is primarily used as a solvent in vapor degreasing. It is also used for extracting caffine from coffee, as a dry cleaning agent, and as a clinical intermediate in the production of pesticides, waxes, gums resins, tars, paints, and varnishes.

Classification

The EPA has classified TCE in Group B2: sufficient evidence in animals and inadequate evidence in humans. According to the U.S. EPA's preliminary risk assessment from ambient air exposures, public health risks are significant.

Health Effects

TCE is a poison by inhalation and intravenous and subcutaneous routes. It is moderately toxic by ingestion. Mutagenic data exist. It is an experimental teratogen, carcinogen, and tumorigen. It is a strong skin and eye irritant. Inhalation of high concentrations cause narcosis and anesthesia. A form of addiction has been observed in exposed workers. Prolonged inhalation of moderate concentrations causes headache and drowsiness. Fatalities following severe, acute exposure have been attributed to ventricular fibrillation resulting in cardiac failure. There is also damage to the liver and other organs from chronic exposure. High concentrations can have a narcotic effect. TCE has been found to induce hepto cellular carcinomas in tests on mice.

Oral and Inhalation Exposure

Both oral and inhalation reference dose assessments are pending. A risk assessment for this chemical is under review by a U.S. EPA assessment group. Significant increases in the incidence of liver tumors have been reported in B6C3F1 mice of both sexes. Malignant lymphomas and pulmonary adeno carcinomas were also reported in mice. Oral slope factor is 1.1E-2 (mg/kg/day)"' inhalation slope factor is 1.7E-2 (mg/kg/day)"l.

Toxicity to Human Health and Animals

The U.S. EPA indicated that it intends to add TCE to the list of hazardous air pollutants for which emission standards under the Clean Air Act will be established. A

maximum contaminant level goal (MCLG) for drinking water is established at 0 mg/1 based on carcinogenic effects. A maximum contaminant level (MCL) for drinking water is calculated to be 5 iag/1.

The ambient water quality criteria (AWQC) for human health is calculated to be 2.7 E+0 jag/1 for water and fish consumption. For maximum protection from the potential carcinogenic properties of this chemical, the ambient water concentration should be zero.

The AWQC have established acute toxicity levels for freshwater and marine organisms to be 4.5 E+4 ng/1 and 2.0 E+3 ng/1, respectively. Chronic toxicity levels have not been established for agiiatic organisms.

TECHNICAL PROFILE

XYLENES, TOTAL

Xylene C8H10, commonly known as dimethylbenzene, is used as a solvent, a raw material for production of benzoic acid, phthalic anhydride, and as isophthalic, and terephthalic acid, and as dimethyl esters used in the manufacture of polyester fibers, dyes, and other organics. It is also used for sterilizing catgut. Xylenes exist in three isomeric forms, orthometa, and para-xylene.

Classification

The weight of evidence classification for human carcinogenicity is Class D: not considered a human carcinogen based on oral studies in rats which did not result in a significant increase in tumor responses.

Health Effects

Xylenes is a poison by ingestion and inhalation. It may affect the central nervous system (CNS), eyes, gastrointestinal tract, blood, liver, kidneys, and skin. Xylene vapors may cause irritation to the eyes, nose, and throat. Repeated or prolonged skin contact with xylene may cause drying and defatting of the skin, which may lead to dermatitis. Liquid xylene is irritating to the eyes and mucous membranes, and aspiration may cause chemical pneumonitis, pulmonary edema, and hemorrhage. Repeated exposure of the eyes to high concentrations of xylene vapor may cause reversible eye damage.

Acute exposure to xylene vapor may cause CNS depression and minor reversible effects on liver and kidneys. At high concentrations xylene vapor may cause dizziness, staggering, drowsiness, and unconsciousness. At extremely high concentrations, breathing xylene vapors may cause pulmonary edema anorexia, nausea, vomiting, and abdominal pain.

Oral Exposure

The U.S. EPA (1984) reported an oral reference dose of 2 mg/kg/day based on a rat dietary observing an acute effect level of 200 ppm or 10 mg/kg/day as defined by Bowers et al (1982) in a six-month study. A National Technical Report on the toxicology and carcinogenesis of xylenes inhibited hyperactivity, a manifestation of CNS toxicity (NTR, 1986). Groups of Fisher 344 rats and B6C3F1 mice were given various doses for five days per week for 103 weeks. Clinical signs of toxicity, body

weight gain, and mortality were observed. There was a dose-related increase in mortality in male rats and the increase was significantly greater in the high dose groups compared with controls. The reference dose based on the NTP study is preferred because it is based on a chronic exposure in two species by a relevant route of administration. Comprehensive histology was performed. Xylene is fetotoxic and teratogenic in mice at high oral doses (Nawrot and Staples, 1981, Marks et al., 1982), but the reference dose should be protective of the effects.

No human carcinogenic data are available, and animal carcinogenic data are inadequate. Maltoni et al. (1985) in a limited study reported higher incidences of malignant tumors in male and female Sprague-Dawley rats treated by gavage with xylene in olive oil at 500 mg/kg/day. Berenblum (1941) reported that "undiluted" xylene applied at weekly intervals produced one tumor-bearing animal out of 40 after 25 weeks in skin-painting experiments in mice. No control groups were described. Pound (1970) reported negative results in initiation-promotion experiments with xylene as the initiator and custom oil as the promotor.

The frequency of sister chromatid exchanges and chromosomal aberrations were nearly identical between a group of 17 paint industry workers exposed to xylene and their respective referents (Haqlund et al., 1980). Xylene caused no increase in the number of sister chromatid exchanges in human lymphocytes. Studies indicate that xylene isomers, technical grade or mixed, are not mutagenic in tests with Salmonella typhimurium (Florin et al., 1980) nor in mutant revision assays with Escherichia coli (McCarroll et al., 1981). Technical grade xylene, but not-o-and m-xylene, was weakly mutagenic in Drosophila recessive lethal tests. Chromosomal aberrations were not increased in bone marrow cells of rats exposed to xylenes by inhalation (Donner et al., 1980).

Inhalation Exposure

No quantitative estimate of carcinogenic risk from inhalation exposure is available. An inhalation reference dose of 4E-1 mg/day (about 0.06 mg/kg/day) based on an inhalation study (Jenkins et al., 1970) using rats, guinea pigs, monkeys, and dogs exposed to o-xylene at 3,358 mg/m3, eight hours/day, five days/week for six weeks at 337 mg/m3 continuously for 90 days was derived by the U.S. EPA (1985). Death in rats and monkeys and tremors in dogs occurred at the highest dose, whereas no effects were observed in the 337 mg/m3 continuous exposure group.

Toxicity to Human Health and Animals

A maximum contaminant level goal (MCLG) for drinking water of 0.44 mg/1 for xylene is proposed based on a drinking water equivalent level of 2.2 mg/L and an assumed frinking water contribution of 20 percent. A drinking water equivalent level (DWEL) of 2.2 mg/1 was calculated from a no observed acute effect level of 337 mg/m3 for body weight, hemotology, and hisopathologic effects (IRIS, 1990). No criteria have been set but the U.S. EPA has suggested a permissible ambient goal of 6,000 pg/1 based on health effects (Sittig, 1985).

TECHNICAL PROFILE

ACENAPHTHENE

Acenaphthene is one of the polycyclic aromatic hydrocarbon (PAH) compounds. Because it is formed when gasoline, garbage, or any animal or plant material burns, it is usually found in smoke and soot. This chemical combines with dust particles in the air and is carried into water and soil and onto crops. Acenaphthene is found in coal tar pitch used by industry as an adhesive.

People may be exposed to acenaphthene from environmental sources such as air, water, and soil, and from cigarette smoke and overcooked food. Typical exposures are not usually to acenaphthene alone, but to a mixture of similar chemicals.

Classification

This substance/agent has not been evaluated by the U.S. EPA for evidence of human carcinogenic potential.

Oral Exposure

Mouse oral subchronic studies with acenaphthene had toxicological evaluations that included body weight changes, altered food consumption, mortality, clinical pathological evaluations (includings hematology and clinical chemistry), organ weights changes and histopathological evaluations of target organs. Liver weight changes accompanied by microscopic alterations (cellular hypertrophy) were noted in both mid- and high-dose animals and seemed to be dose-dependent. Additionally, high-dose males and mid- and high- dose females showed significant increases in cholesterol levels. On intraperitoneal administration in rats (species/number/sex unspecified), naphthalene was more toxic than acenaphthene and acenaphthylene. wo LD/50 values were reported, but it is unclear to which of the three chemicals these values belonged.

Inhalation Exposure

Intraperitoneal and intratracheal administration of naphthalene, acenaphthene, and acenaphthylene produced monotypic effects in the form of vascular disorders, and degeneration in the internal organs and central nervous system. Inflammatory changes were also observed in the lungs; the degree was the same for all three substances. Splenic degeneration was noted among the unscheduled deaths in this study. It was concluded that chronic inhalation of acenaphthene and acenaphthylene had more pronounced toxic effects than naphthalene.

Toxicity to Human Health and animals

U.S. EPA. 1990. Drinking Water Criteria Document for Polycyclic Aromatic Hydrocarbons (PAHs). Prepared by the Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH for the Office of Drinking Water, Washington, DC. ECAO-CIN-D010, September, 1990. (Final Draft)

TECHNICAL PROFILE

ACENAPHTHYLENE

Acenaphthylene is one of the polycyclic aromatic hydrocarbon (PAH) compounds. Because it is formed when gasoline, garbage, or any animal or plant material burns, it is usually found in smoke and soot. This chemical combines with dust particles in the air and is carried into water and soil and onto crops. Acenaphthylene is found in coal tar pitch used by industry as an adhesive.

People may be exposed to acenaphthylene from environmental sources such as air, water, and soil, and from cigarette smoke and overcooked food. Typical exposures are not usually to acenaphthylene alone, but to a mixture of similar chemicals.

Classification

Classification — D; not classifiable as to human carcinogenicity Basis — Based on no human data and inadequate data from animal bioassays.

Oral Exposure

On intraperitoneal administration in rats (species/number/sex unspecified), naphthalene was more toxic than acenaphthene and acenaphthylene. Two LD/50 values were reported, but it is unclear to which of the three chemicals these values belonged.

Inhalation Exposure

Intraperitoneal and intratracheal administration of naphthalene, acenaphthene, and acenaphthylene produced monotypic effects in the form of vascular disorders, and degeneration in the internal organs and central nervous system. Inflammatory changes were also observed in the lungs; the degree was the same for all three substances. Splenic degeneration was noted among the unscheduled deaths in this study. It was concluded that chronic inhalation of acenaphthene and acenaphthylene had more pronounced toxic effects than naphthalene.

Toxicity to Human Health and Animals

U.S. EPA. 1990. Drinking Water Criteria Document for Polycyclic Aromatic Hydrocarbons (PAHs). Prepared by the Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH for the Office of Drinking Water, Washington, DC. ECAO-CIN-D010, September, 1990. (Final Draft)

TECHNICAL PROFILE

ANTHRACENE

Anthracene is one of the polycyclic aromatic hydrocarbon (PAH) compounds. Because it is formed when gasoline, garbage, or any animal or plant material burns, it is usually found in smoke and soot. This chemical combines with dust particles in the air and is carried into water and soil and onto crops. Anthracene is found in coal tar pitch used by industry as an adhesive.

People may be exposed to naphthalene from environmental sources such as air, water, and soil, and from cigarette smoke and overcooked food. Typical exposures are not usually to anthracene alone, but to a mixture of similar chemicals.

Classification

USEPA weight-of-evidence classification— D, not classifiable as to human carcinogencity on the basis that no human data and inadequate data from animal bioassays exists.

Oral Exposure

Anthracene administered to groups of mice by oral gavage produced no treatment-related effects. The no- observed-effect level (NOEL) is the highest dose tested (1000 mg/kg/day). Confidence in the oral exposure data base is low, because of the lack of adequate toxicity data in a second species and developmental/reproductive studies. Low confidence in the RfD follows.

Inhalation Exposure

No information exists at this time.

Toxicity to Human Health and Animals

U.S. EPA. 1990. Drinking Water Criteria Document for Polycyclic Aromatic Hydrocarbons (PAHs). Prepared by the Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH for the Office of Drinking Water, Washington, DC. ECAO-CIN-D010, September, 1990. (Final Draft)

TECHNICAL PROFILE

BENZOIC ACID

Benzole Acid, C7HS02, is a benzene carboxylic acid, and is used in preserving foods, fats, juices, dyes, and as standard in chemical analysis.

Classification

Benzoic acid is not classified as a human carcinogen. The weight of evidence for classification as to human carcinogenicity is classified as Group D: not classifiable as to human carcinogenicity based on no human data and inadequate data from animal bioassays.

Health Effects

Benzoic acid is a mild irritant to skin, eyes, and mucous membranes. It is a poison by vapor inhalation. Benzoic acid and sodium benzoate have been tested for mutagenicity or genotoxicity with no positive results reported (Litton Bionetics, 1975). Sodium benzoate appeared to have no maternal toxicity, fetal toxicity, or teratogenic potency in mice, rats, hamsters, or rabbits when administered (FDRL, 1972).

Oral Exposure

Studies using humans indicate that laboratory animals are inappropriate models for the toxicity of benzoic acid in humans. The Federal Drug Administration (FDA) (1973) estimated daily per capita intakes of 0.9-34 mg for benzoic acid and 34-328 mg for sodium benzoate. No reports of toxic effects were noted in humans, and these compounds have status by the FDA. The upper ranges are considered no observed acute effect levels (NOAELs) for benzoic acid. In the stomach, both benzoic acid and sodium benzoate exist in the ionized form of a benzoate. Both benzoic acid and sodium benzoate are absorbed rapidly and completely by the gastrointestinal (GI) tract. Therefore, exposure to sodium benzoate is essentially equivalent to exposure to benzoic acid. The only chronic and oral data available (Shtenberg and Ignat'ev, 1970) observed no effects on body weight, survival, or microscopic pathology. Long-term dietary studies resulted in no signs of toxicity and no adverse reproductive effects over four generations (Marquardt, 1960). The 40 mg/kg/day in mice (Shtenberg and Ignat'ev) is considered to be the low observed adverse effect level (LOAEL) application. A RfD of 4E+0 mg/kg/day is based on this value. Wiley and Bigelow (1908) observed irritation,

discomfort, weakness, and malaise in humans given oral doses of less than or equal to 1.75 g/day over a 20-day period. The reference dose is well below these doses; Toth's (1984) lifetime study, based on results of a subchronic study, considered four and eight percent to be too toxic. The treatment had no apparent effect on survival of tumor incidence. Tumor incidences were not reported for untreated mice or for mice treated with benzoic acid only. Dinerman and Ignat'ev (1966) reported an increase susceptibility of mice to carcinoma development following intraperitoneal inoculation with Erlich ascites carcinoma cells. Benzoic acid has been tested for mutogenicity or genotoxicity in prokaryotes (Me Cann, 1975); eukaryotes (Litton, 1974); and several mamalian test systems with no positive results reported.

Inhalation Exposure

No quantitative estimate of carcinogenic risk from inhalation exposure is presently available.

Toxicity to Human Heath and Animals

No ambient water quality criteria have been established for benzoic acid levels in relation to human health and aquatic organisms.

TECHNICAL PROFILE

BENZO (A) PRYRENE

Classification

Benzo (a) pyrene (B(a)P) is a polycyclic aromatic hydrocarbon (PAH) compound. it is formed when any organic material burns and is usually found in smoke and soot as a combustion by-product. B(a)P is found in coal tar pitch used by industry, and is found in creosote.

Health Effects

B(a)P causes cancer in laboratory mice when applied to their skin. B(a)P weight of evidence is B2 because of sufficient evidence of carcinogenciity in experimental animals, but inadequate evidence of cancer in humans from epidemiologic studies.

Oral Exposure

Shore term and intermediate oral exposure to very high levels of B(a)P resulted in death in experimental animals fed B(a)P in the diet. The induction of cancer is the kkey endpoint of toxicity following chronic exposures to lower dates of B(a)P the diet. Lethal effects from high doses of B(a)P were caused by bone marrow depression. There is no information available for the potential of human carcinogenciity following oral B(a)P exposure. Studies with experimental animals have produced luke,ia and tumors of the fore stomach and lung following intermediate expsoures in mice. The slope factor calculated from this study is currently under review but has been used in the interim.

Inhalation Expsure

No short term or intermediate inhalation expsoure effects are available for B(a)P. The induction of cancer is the key long term effect. This observation is based upon studies in humans are available because B(a)P does not exist in a pure form in nature and is always found in mixtures with other suspected carcinogens.

Toxicity to Human Health and Animals

B(a)P is a moderately potent experimental carcinogen in many species by many routes of exposure. There are no reports directly correlating human B(a)P exposure and tumor development, although humans are likely to be exposed to all routes. There are a number of reports associating human cancer and exposure to mixtures of PAHs that include B(a)P. In view of these observations and its well established carcinogenic activity in laboratory animals, it is reasonable to conclude that B(a)P would be expected to be carcinogenic in humans by all rotes of exposure.

TECHNICAL PROFILE

BENZO (B) FLUORANTHENE

Benzo (b) fluoranthene (B(b)F) in its pure form is a colorless crystallize solid at room temperature and has a molecular weight ofg 252.32 g/mole. It has a vapor pressure of 5 x 10"7 and an octanol water coefficient pf 1/15 x 10s, and is therefore expected to have poor mobility in the environment. B(b)F is a polycyclic aromatic hydrocarbon that is formed during combustion of fossil fuels and organic material. it is found environmentally in mixtures with other PAH compounds including B(a)P.

CLASSIFICATION

The USEPA weight of evidence classification for B(b)F is C- possible human carcinogen. Limited evidence of carcinogenicity in animals in the absence of positive human data.

Health Effects

Thre are no data available to assess significant exposure levels of B(b)F alone for humans reports of adverse health effects such as carinogenicity by the inhalation and dermal routes of exposure do exist for mixtures that include B(b)F thus providing some information to qualitatively assess the role of B(b)F as a human carcinogen.

Oral Exposure

No information was found in the available literature concerning the effects of B(b)F following oral exposure.

Inhalation Exposure

No information was found in the available literature concerning the effects of B(b)F following inhalation exposure.

toxicity to Human Health and Animals

No information has been found about specific levels of B(b)F that have caused harmful effects in humans or animals after ingestion, inhalation, or dermal contact. The carcinogenicity of B(b)F has not abeen adequately studied there are no reports directly correlating human B(b)F exposure and tumor development, although humans are likely to be exposed by all routes. there are a number of reports associating human cancer with exposure to mixtures of PAHs that include B(b)F is a skin carcinogen in animals following dermal application, and a lung carcinogen following intratracheal instillation. It is likely that B(b)F would cause cancer in humans as well.

TECHNICAL PROFILE

BENZO(G,H,I)PERYLENE

Benzo[g,h,i]perylene is one of the polycyclic aromatic hydrocarbon (PAH) compounds. Because it is formed when gasoline, garbage, or any animal or plant material burns, it is usually found in smoke and soot. This chemical combines with dust particles in the air and is carried into water and onto soil and crops. Benzo[g,h,i]perylene is found in coal tar pitch used by industry as an adhesive.

People may be exposed to benzo[g,h,ilperylene from environmental sources such as air, water, and soil, and from cigarette smoke and overcooked food. Typical exposures are not usually to benzo[g,h,i]perylene alone, but to a mixture of similar chemicals.

CLASSIFICATION

USEPA weight-of-evidence classification— D; not classifiable as to human carcinogenicity based upon no human data and inadequate animal data from lung implant, skin-painting and subcutaneous injection bioassays.

Oral Exposure

Not available at this time.

Inhalation Exposure

Benzo[g,h,i]perylene appeared to increase lung epidermoid tumors when administered with trioctanonin in a lung implant study. In a lifetime implant study, 3-month-old female Osborne-Mendel rats (34 to 35/group) received a lung implant of benzo[g,h,i]perylene. Epidermoid carcinomas in the lung and thorax were observed. The apparent increased incidence of tumors was not statistically significant and no distant tumors were seen.

Toxicity to Human Health and Animals

U.S. EPA. 1990. Drinking Water Criteria Document for Polycyclic Aromatic Hydrocarbons (PAHs). Prepared by the Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH for the Office of Drinking Water, Washington, DC. Final Draft. ECAO-CIN-DOlO, September, 1990.

TECHNICAL PROFILE

BENZO(K)FLUORANTHENE

Benzo[k]fluoranthene is one of the polycyclic aromatic hydrocarbon (PAH) compounds. Because it is formed when gasoline, garbage, or any animal or plant material burns, it is usually found in smoke and soot. This chemical combines with dust particles in the air and is carried into water and onto soil and crops. Benzo[k]fluoranthene is found in coal tar pitch used by industry as an adhesive.

People may be exposed to benzo[k]fluoranthene from environmental sources such as air, water, and soil, and from cigarette smoke and overcooked food. Typical exposures are not usually to benzo[k]fluoranthene alone, but to a mixture of similar chemicals.

Current theories on mechanisms of metabolic activation of polycyclic aromatic hydrocarbons are consistent with a carcinogenic potential for benzo[k]fluoranthene. Benzo[k]fluoranthene has a "bay-region" structure. It is metabolized by mixed function oxidases to reactive "bay­region" diol epoxides that are mutagenic in bacteria and tumorigenic in mouse skin painting assays.

CLASSIFICATION

The USEPA weight-of-evidence classification for benzo[k]fluoranthene is B2 probable human carcinogen on the basis that no human data and sufficient data from animal bioassays exists.

Oral Exposure

No adequate information exists on acute or chronic effects from oral exposure to benzo[k]fluoranthene.

Inhalation Exposure

No adequate information exists on acute or chronic effects from inhalation exposure to benzo[k]fluoranthene.

Toxicity to Human Health an Animals

Benzo[k]fluoranthene produced tumors after lung implantation in mice and when administered with a promoting agent in skin-painting studies. Equivocal results have been found in a lung adenoma assay in mice. Benzofk]fluoranthene is mutagenic in bacteria. Although there are no human data that specifically link exposure to benzo[k]fluoranthene to human

cancers, benzo[k]fluoranthene is a component of mixtures that have been associated with human cancer. These include coal tar, soots, coke oven emissions and cigarette smoke.

Lung adenomas were found in treated male (1/16) and female (3/18) mice, whereas none were reported for the controls. This assay is considered to be a short-term, in vivo, lung tumor assay.

Benzo[k]fluoranthene has yielded positive results for initiating activity in several mouse skin-painting assays. A single dermal application of 11 mg benzo[k]fluoranthene to 20 Swiss mice in a 63-week study did not induce tumors (Van Duuren et al., 1966). However, when the same dose was followed by promoting treatments with croton resin, 18/20 animals developed papillomas and 5/20 developed carcinomas.

TECHNICAL PROFILE

BENZ(A)ANTHRACENE

Benz[a]anthracene is one of the polycyclic aromatic hydrocarbon (PAH) compounds. Because it is formed when gasoline, garbage, or any animal or plant material burns, it is usually found in smoke and soot. This chemical combines with dust particles in the air and is carried into water and onto soil and crops. Benz[a]anthracene is found in coal tar pitch used by industry as an adhesive.

People may be exposed to benz[a]anthracene from environmental sources such as air, water, and soil, and from cigarette smoke and overcooked food. Typical exposures are not usually to benz[a]anthracene alone, but to a mixture of similar chemicals.

Current theories on mechanisms of metabolic activation of polycyclic aromatic hydrocarbons are consistent with a carcinogenic potential for benz[a]anthracene. Benz[a]anthracene has a "bay-region" structure. It is metabolized by mixed function oxidases to reactive "bay­region" diol epoxides that are mutagenic in bacteria and tumorigenic in mouse skin painting assays.

CLASSIFICATION

The weight-of-evidence classification for benz[a]anthracene is B2— probable human carcinogen based on no human data and sufficient data from animal bioassays.

Oral Exposure

No adequate information exists on acute or chronic effects from oral exposure to benz[a]anthracene.

Inhalation Exposure

No adequate information exists on acute or chronic effects from inhalation exposure to benz[a]anthracene.

Toxicity to Human Health and Animals

Benz[a]anthracene produced tumors in mice exposed by gavage, intraperitoneal, subcutaneous or intramuscular injection, and topical application. Benz[a]anthracene produced mutations in bacteria and in mammalian cells, and transformed mammalian cells in culture.

Although there are no human data that specifically link exposure to benz[a]anthracene to human cancers, benz[a]anthracene is a component of mixtures that have been associated with human cancer. These include coal tar, soots, coke oven emissions and cigarette smoke.

U.S. EPA. 1990. Drinking Water Criteria Document for Polycyclic Aromatic Hydrocarbons (PAHs). Prepared by the Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH for the Office of Drinking Water, Washington, DC. Final Draft. ECAO-CIN-D010, September, 1990.

TECHNICAL PROFILE

BENZYL ALCOHOL

Benyzl alcohol is a constituant of jasmine, hyacinth, and ylang-ylang oils, Peru and tolu balsams. In pure form, it is a liquid with a slight aromatic odor.

Classification

Benzyl alcohol is not classified for carcinogenicity by U.S. EPA.

Oral Exposure

Benzyl alcohol has an oral LDSo of 3.1 g/kg in rats (MERCK, 1989).

Inhalation Exposure

No information is available.

Toxicity to Human Health and Animals

Benzyl alcohol is used in perfumery and flavoring. It is used in microscopy as an embedding medium.

TECHNICAL PROFILE

BIS(2-ETHYLHEXYL)PHTHALATE

Bis(2-ethylhexyl)phthalate, C6H4 (COOCH2C2HsCH2CH2CH2CHj)2, is a colorless oily liquid with almost no odor. It is produced by the reaction of 2-ethylhexyl alcohol and phthalic anhydride. It is used as a plasticizer for resin and in the manufacture of organic pump fluids.

Classification

The U.S. EPA weight of evidence has classified BEHP in Group B2: a probable human carcinogen. This is based on studies where orally administered BEHP produced significant dose-related increases in liver tumor responses in rats and mice of both sexes.

Health Effect

BEHP can be inhaled, ingested, and be a skin and eye irritant. It may affect the upper respiratory and gastrointestinal systems. Symptoms may include irritation of the eyes and mucous membrane; nausea; and diarrhea (Sittig, 1985).

Oral Exposure

Carpenter (1953) provided a chronic oral toxicity of BEHP for rats, guinea pigs, and dogs. No treatment-related effects were observed on mortality, body weight, kidney weight, or gross pathology and histopathology of kidneys, liver, lung, spleen, or testes. Significant increases in relative liver weights were observed in both groups of females treated. A low observed adverse effect level (LOAEL) was established to be 19 mg/kg/day based on the sensitivity of the guinea pigs. From this, a Rfd of 2E-2 mg/kg/day has been calculated.

Mice were examined for adverse fertility and reproductive effects using a continuous breeding protocol. BEHP was a reproductive toxicant in both sexes, significantly decreasing fertility and the proportion of pups born alive and induced damage to the seminiferous tubules. BEHP has been observed to be both fetotoxic and teratogenic (Singhe, 1972).

Theiss (1978) conducted a mortality study in relation to workers, which was inconclusive, and no other data have been established to evaluate human carcinogenicity.

Studies indicate that DEHP is not a direct-acting mutagen in either a forward mutation assay in Salmonella typhemurium (See, 1982) or the rec assay in Bacillus subtilis (Tomitta, 1982). MEHP, the monoester form of DEHP, and a metabolite are positive in the rec assay and in the reverse mutation assay in Salmonella. MEHP produced chromosomal aberrations and sister chromatid exchanges in the absence of exogenous metabolism. Both DEHP and MEHP induced chromosomal aberrations and morphological transformation (TOMITA, 1982).

The quantitative estimate of carcinogenic risk from oral exposure of BEHP has an oral slope factor of 1.4E-2 (mg/kg/day) with a drinking water unit risk of 4.OE-7 ng/1.

Inhalation Exposure

A quantitative dose for chronic inhalation exposure is not available (IRIS, 1990).

Toxicity to Human Health and Animals •

The ambient water quality criteria (AWQC) for human health are 1. 5E+4 |jg/l and 5E+4 ng/1 for water and fish consumption, respectively. Acute toxicity levels for freshwater and marine organisms are 9.4E+2 pg/1 and 2.944E+3 pg/1, respectively. Chronic toxicity levels are 3E+0 ng/1 and 3.4E+0 |jg/l for freshwater and marine organisms, respectively.

TECHNICAL PROFILE

CHRYSENE

Chrysene is one of the polycyclic aromatic hydrocarbon (PAH) compounds. Because it is formed when gasoline, garbage, or any animal or plant material burns, it is usually found in smoke and soot. This chemical combines with dust particles in the air and is carried into water and onto soil and crops. Chrysene is found in coal tar pitch used by industry as an adhesive.

People may be exposed to chrysene from environmental sources such as air, water, and from tobacco smoke and overcooked food. Typical exposures are not usually to chrysene alone, but to mixtures of similar compounds.

Current theories on mechanisms of metabolic activation of polycyclic aromatic hydrocarbons are consistent with a carcinogenic potential for chrysene. Chrysene has a "bay-region" in structure. It is metabolized by mixed function oxidases to reactive "bay-region" diol epoxides that are mutagenic in bacteria and tumorigenic in mouse skin painting assays and when injected into newborn mice.

Classification

The USEPA weight-of-evidence classification for chrysene is B2, a probable human carcinogen on the basis that no human data and sufficient data from animal bioassays exists.

Oral Exposure

There are no adequate data for long or short term chronic or acute effects of chrysene through oral exposure.

Inhalation Exposure

There are no adequate data for long or short term chronic or acute effects of chrysene through inhalation exposure.

Toxicity to Human Health and Animals

Chrysene produced carcinomas and malignant lymphoma in mice after intraperitoneal injection and skin carcinomas in mice following dermal exposure. In mouse skin painting assays chrysene tested positive in both initiation and complete carcinogen studies. Chrysene produced chromosomal abnormalities in hamsters and mouse germ cells after gavage exposure, positive responses in bacterial gene mutation assays and transformed mammalian cells exposed in culture. It was shown

to be a complete carcinogen. Chrysene has produced positive results for initiating activity in several mouse strains when applied in combination with various promoting agents producing skin papillomas and carcinomas.

Although there are no human data that specifically link exposure to chrysene to human cancers, chrysene is a component of mixtures that have been associated with human cancer. These include coal tar, soots, coke oven emissions and cigarette smoke.

The 1990 Drinking Water Criteria Document for Polychlorinated Aromatic Hydrocarbons has received Agency and external review.

TECHNICAL PROFILE

DIBENZOFURAN

Dibenzofuran is formed as a byproduct in the manufacture of chlorinated herbicides, and is produced during the combustion of PCBs. It is not found in a pure form, but as a component of mixtures of dioxins and furans produced in a similar fasion.

Classification

The USEPA weight-of-evidence classification of dibenzofuran is D, not classifiable as to human carcinogenicity based upon no human data and no animal data for dibenzofuran alone.

Oral Exposure

No studies for oral exposure to pure dibenzofuran were found.

Inhalation Exposure

No inhalation studies were found.

Toxicity to Human Health and Animals

There are no data on the possible carcinogenicity of dibenzofuran alone in humans. Studies have evaluated exposure to a mixture of polychlorinated biphenyls (PCBs), polychlorinated dibenzofurans (PCDFs) and polychlorinated quinones (PCQs) by consumption of contaminated rice oil. However, these studies have limited value because they do not assess dibenzofuran or correlate exposure with cancer risk. Additionally, because of the multiple exposures, the extent to which the various components contributed to the increase in cancer mortality cannot be determined.

No animal carcinogenicity data on dibenzofuran are currently available. U.S. EPA (1986) noted that the biological activity of PCDFs varies greatly, so that risk assessment of dibenzofuran by analogy to any of these more widely studied compounds would not be recommended.

In a comparison of Toxic Equivalency Factor (TEF) values for chlorinated dibenzofurans, mono-, di- and tri-chlorinated dibenzofuran had TEF values of 0 (U.S. EPA, 1989). Based on these results and because toxicity of polychlorinated dibenzofurans (PCDF) depends on the number of chlorine substituents and their position (U.S. EPA, 1986), the TEF for dibenzofuran, with no chlorine substituents, is set equal to 0.

U.S. EPA. 1986. Health Assessment Document for Polychlorinated Dibenzofurans. Prepared by the Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH for the Office of Air Quality Planning and Standards, Research Triangle Park, NC. EPA 600/8­86/018A. NTIS PB86-221256/AS.

TECHNICAL PROFILE

DIBENZ(A,H)ANTHRACENE

Dibenz(a,h,)anthracene is one of the polycyclic aromatic hydrocarbon (PAH) compounds. Because it is formed when fossil fuels, garbage, or any other plant or animal material is burned, it is usually found in smoke and soot. This chemical combines with dust particles in the air and is carried into water and onto soil and crops. Dibenz(a,h)anthracene is found in coal tar pitch used by industry as an adhesive.

Although there are no human data that specifically link exposure to dibenz[a,h]anthracene with human cancers, it is a component of mixtures that have been associated with human cancer. These include coal tar, soots, coke oven emissions, over cooked food and tobacco smoke.

Current theories on mechanisms of metabolic activation of polycyclic aromatic hydrocarbons are consistent with a carcinogenic potential for dibenz[a,h]anthracene. Dibenz[a,h]anthracene has a "bay-region" structure. It is metabolized by mixed-function oxidases to dihydrodiols that are mutagenic in bacteria and tumorigenic in mouse skin painting assays and when injected into newborn mice

Classification

USEPA weight-of-evidence classification for dibenz(a,h)anthracene is B2; probable human carcinogen based on no human data and sufficient data from animal bioassays.

Oral Exposure

Dibenz[a,h]anthracene has been shown to be carcinogenic when administered to mice by the oral route. Mice developed pulmonary adenomas, pulmonary carcinomas, mammary carcinoma, and hemangioendothelioma.

Mammary carcinomas were observed in two strains of female mice following gavage with dibenz[a,h]anthracene. A single large dose of dibenz[a,h]anthracene in polyethylene glycol produced forestomach papillomas in male mice after 30 weeks. In this short- term study no mice developed tumors when treated with PEG alone.

Inhalation Exposure

There is no information on inhalation exposure.

Toxicity to Human Health and Animals

Dibenz[a,h]anthracene produced carcinomas in mice following oral or dermal exposure and injection site tumors in several species following subcutaneous or intramuscular administration. Dibenz[a,h]anthracene has induced DNA damage and gene mutations in bacteria as well as gene mutations and transformation in several types of mammalian cell cultures.

The 1990 Drinking Water Criteria Document for Polycyclic Aromatic Hydrocarbons has received Agency and external review,

TECHNICAL PROFILE

1,2 DICHLOROBENZENE

1,2-Dichlorobenzene CSH4C12, (1,2-DCB), is a colorless pale liquid that is used as a process solvent in the manufacturing of toluene disisocyanate and as an intermediate in the synthesis of dye stuffs, herbicides, and degreasers.

Classification

This chemical is among those substances being evaluated by the U.S. EPA for evidence of human carcinogenic potential. This does not imply that this chemical is necessarily a carcinogen. A risk assessment summary will be included when completed.

Health Effects

Human exposure to 1,2-DCB is reported to cause hemolytic anemia and liver necrosis. Dichlorobenzenes in general are toxic to nonhuman mammals, birds, and aquatic organisms and impart an offensive taste and odor to water (Sittig, 1985). Persons with pre-existing pathology (hepatic, renal, and central nervous system) or metabolic disorders and are taking certain drugs (hormones or other metabolically active), might be considered risks from exposure to 1,2-DCB. Irritation of eyes and nose, liver and kidney damage, and skin blisters may appear upon 1,2-DCB exposure.

Oral Exposure

Simultaneously taking into consideration a 13-week and two-year National Toxicology Program (NTP), the no observed adverse effect level (NOAEL) of 120 mg/kg/day is supported. 1,2-DCB in corn oil was given by gavage to rats/mice at various dose levels. An increase in renal tubular regeneration in high-dose male mice was observed. No other treatment-related renal lesions were observed in other species (NTP, 1985). Liver necrosis was found in mice and rats given 250 mg/kg/day (NTP, 1985). Deaths, degeneration, necrosis in liver, lymphocyte depletion in spleen and thymus, renal tubular degeneration (male rats only), and slight decreases in hemoglobin, hematocrit, and red blood cell counts were induced with 500 mg/kg/day. The oral Rfd is 9E-2 mg/kg/day.

Inhalation Exposure

Studies by inhalation of 1,2-DCB at various levels observed body weight gains in rats, and spleen weights in guinea pigs were reduced (Hollingsworth, 1958). Pregnant rats and New Zealand rabbits exposed by inhalation at various dose-level concentrations exhibited body weight loss and an increase in liver weight at 400 ppm. No development toxicity was evident at any dose. The reference dose for chronic inhalation exposure is 4E-2 mg/kg/day (HEAST, 1990).

Toxicity to Human Health and Animals

To protect freshwater aquatic life, levels of 1,120 ng/1 on an acute toxicity basis and 763 ng/1 on a chronic basis have been calculated. To protect saltwater aquatic life, a dose of 1,970 pg/1 on an acute toxicity basis was established. All isomers are valued at 400 pg/l for human health levels (Sittig, 1985).

TECHNICAL PROFILE

1,3-DICHLOROBENZENE

1,3-Dichlorobenzene is one of a group of chlorinated benzene compounds. These compounds are rarely found in their pure form, but usually occur as mixtures. They are by-products of the manufacture of dyes and pesticides. Although little is known about the toxicity or health effects of 1,3-dichlorobenzene alone, it is thought that the effects are generally similar to those of chlorobenzene.

Classification

The USEPA classification for 1,3 Dichlorobenzene is D, not classifiable as to human carcinogenicityon the basis of no human data, no animal data and limited genetic data.

Oral Exposure

No information is available at this time.

Inhalation Exposure

No information is available at this time.

Toxicity to Human Health and to Animals

No information is available at this time.

TECHNICAL PROFILE

1, 4-DICHLOROBENZENE

In pure form, 1, 4-dichlorobenzene is a white chrystaline material that is volatile at room temperatures with a characteristic penetrating odor. It is used as an insecticidal fumigant, popular for protecting clothes against moths.

Classification

Not classified for carcinogenicity by U.S. EPA.

Oral Exposure

1, 4-dichlorobenzene has an oral LDSo of 500 mg/kg in rats (MERCK, 1989).

Inhalation Exposure

No information is available.

Toxicity to Human Health and Animals

Vapors may cause irritation to skin, throat, and eyes. Prolonged exposure to high concentrations may cause weakness, dizziness, loss of weight, and liver injury may develop (MERCK, 1989).

TECHNICAL PROFILE

DIETHYLPHTHALATE

Diethylphthalate, (DEP), Ci2H1404, is a clear, colorless liquid used as a solvent for cellulose esters; as a vehicle in pesticidal sprays; as a fixative and solvent in perfumery; as an alcohol denaturant; and as a plasticizer in solid rocket propellants.

Classification

The weight of evidence classification, categorized in Group D, does not classify DEP as a human carcinogen. No human carcinogenic data are available, and animal carcinogenic data inadequate. Dietary studies conducted by Brown (1978) were not designed to measure carcinogenic effects. DEP was found to be a weak direct mutagen in forward and reverse mutation assays in Salmonella typhimourium (Leed, 1982). DEP was negative in mammalian cell chromosonal aberration assays (Ishidate and Odashima, 1977). Research indicates that DEP is hydrolyzed to monosters (Rawland et al., 1977). There is limited evidence that DEP is a weak inducer of preroxisome proliferation (U.S. EPA, 1987).

Health Effects

DEP can be poisonous by intravenous route (Sittig, 1985). It is also known to be an experimental teratogen and may be moderately toxic if ingested. It can be an eye irritant and a systemic irritant by inhalation. DEP is a narcotic in high concentrations (Sax, 1987).

DEP has few chronic toxic properties and seems to be devoid of any major irritating or sensitizing effects on the skin. Exposure to heated vapors may produce transient irritation of the nose and throat. Conjunctivitis, corneal necrosis, respiratory tract irritation, dizziness, nausea, and eczema are symptoms cited by others. DEP has been shown to produce mutagenic effects in Ames Salmonella assay. DEP was found to be a weak direct-acting mutagen in forward and reverse mutation assays (Leed, 1982; Rubin et al., 1979; Kozumbo et al., 1982). DEP was negative in mammalian cell chromosomal aberration assays (Ishidate and Odashima, 1977; Tsuchiya and Hattori, 1977). Research indicates that DEP is hydrolyzed to monoesters (Rawland et al., 1977). There is limited evidence that DEP is a weak inducer of peroxisome proliferation (U.S. EPA, 1987). Health hazard assessments for varied exposure durations are not available at this time.

Oral Exposure

A short-term oral toxicity study of DEP in rats was conducted (Brown, 1978). Groups of CD rats (15/sex) were fed various doses of DEP for 16 weeks. Hematological examinations (red blood cell count, hematocrit, hemoglobin) were performed as well as differential white blood cell counts conducted. Food and water intake and body weight were measured for all groups on a weekly basis. Urinalyses were conducted during weeks 2, 6, and 15 or 5 to 15 rats/sex/dose group. After 16 weeks of treatment, autopsy, hematologic and histologic examinations were conducted on all animals.

No changes in behavior or other clinical signs of toxicity were observed. The authors reported significantly less weight gain throughout the duration of the experiment in both sexes given five percent DEP fed to females (5-8 percent decrease) and one percent DEP fed to males. Mean food consumption of the previous groups also decreased (11-23 percent) relative to controls. No significant dose-on-time-related trends in urinalyses or hematology results were found.

Absolute weights of brain, heart, spleen, and kidneys decreased in both sexes fed five percent DEP. Relative weights of the brain, liver, kidneys, stomach and small intestines, and full carcum were significantly greater in both sexes of the 16-week controls. No histologic changes because of treatment were reported.

The oral reference dose receives support from the results of a two-year feeding study using rats (Food Research Laboratories, Inc. 1955). Albino weanling rats (strain not specified) (15/sex) were fed 0, 0.5, 2.5, and 5.0 percent DEP. Animals were maintained for a two-year feeding study using rats (Food Research Laboratories, Inc., 1955). Albino weanling rats (strain not specified) (15/sex) were fed 0, 0.5, 2.5, and 5 percent DEP. Two males and two females/group were examined at 12-week intervals for the following: red and white blood cell counts; differential white count; hemoglobin; blood sugar and nitrogen; and urinalysis. Growth of animals in the five percent treatment group was retarded throughout the study, with no depression of food intake. There was a significant decrease in efficiency of food utilization in this group compared with controls.

Data regarding developmental and reproductive effects are extremely limited (Singh et al., 1972). Skeletal malfunctions were observed in Sprague-Dawloey rats after oral administration on days of gestation. Exposure to DEP

does not appear to affect the reproductive performance of mice after oral administration of 0.25, 1.25, and 2.5 percent DEP for 18 weeks (NTP, 1984). Second-generation breeding pairs exposed to 2.5 percent DEP exhibited increased right epididymes and prostrate weight in males and decreased pituitary weight in females (NTP, 1984). Sufficient numbers of rats of both sexes were employed and multiple endpoints, including histopathology, were studied. Confidence in the study is rated medium.

Inhalation Exposure

No quantitative estimate of carcinogenic risk from inhalation exposure is available (IRIS, 1989).

Toxicity to Human Health and Animals

There are no federal standards but ACGIH (1983/84) has adopted a Time Weight Average (TWA) value of 5 mg/m3 and set STEL of 10 mg/m1. Data are insufficient to draft criteria for the protection of either freshwater or marine organisms. The recommended water quality criterion level for protection of human health is 350 mg/1.

TECHNICAL PROFILE

DI-N-BUTYLPHTHALATE

Classification

Di-n-butylphthalate, CIS H22 04/ is a colorless, oily liquid with a weak aromatic odor. No evidence for classification as to human carcinogenicity is noted. U.S. EPA classification for DBF is categorized in Group D as weight of evidence on the basis that no pertinent data are available to evaluate DBP for carcinogenicity in humans and animals.

Health Effects

DBP can irritate the nasal passages, upper respiratory system, and stomach, and is sensitive to light. No medical conditions have been found for this substance.

Oral Exposure

The reference dose for chronic exposure has been estimated at 1.0 E-l mg/kg/day. Toxicity of butyl phthalate was studied in male Sprague-Dawley rats containing percentages of DBP for an annual period. Most of the animals survived the study with no apparent ill effects with the exception of one-half of the rats receiving the highest dose died within the first week of exposure. There was no effect of treatment on gross pathology or hemotology (Smith, 1953). No histopathologic evaluation was reported. Fetoxicity was observed when mice were fed 2,100 mg/kg/day DEP throughout gestation (Shiota and Nishimura, 1982). An increase in terata of borderline significance was observed in progeny. Diethyl phthalate produces degeneration of the seminiferous tubules, probably as a result of the increased urinary excretion of zinc (Gangolli, 1982). Confidence in the oral reference dose is low because the study by Smith used few animals of one sex only. No mortality rate was observed nor was the cause of death indicated. This is only subchronic bioassay of DBP reported. DBP produced a dose-related acting mutagenic response in an animal study using a modified version of reverse mutation plate incorporation assay in Salmonella, strain TA100 only (Kozumbo et al., 1982). It was a weak, direct-acting mutagen in a forward mutation assay in Salmonella typhemurium (Seed, 1982). DBP was a mutagenic in the mouse lymphoma forward mutation assay only in the presence of metabolic activation (CMA, 1986). DBP showed some evidence of clastogenic activity in Chinese hamster fibroblasts (Ishidate and Odashima, 1977) but was negative in human leukocytes (Tsuchiya and Hattori, 1977). There

is no evidence that DBF induces peroxisome proliferation (U.S. EPA, 1987). No quantitative estimate of carcinogenic risk from oral exposure is available at this time.

Inhalation Exposure

No quantitative estimate of carcinogenic risk from inhalation exposure is available. Varied exposure durations are also not available (IRIS, 1990).

Toxicity to Human Health and Animals

Ambient water quality criteria (AWQC) for human health established a level of 3.4 E+4 ug/1 for water and fish consumption. The value for fish consumption is estimated at 1.54 E+5 |ag/l. These estimates are based on consumption of contaminated aquatic organisms and water. A AWQC level of 1.54 E+5 jag/1 has also been established based on consumption of contaminated aquatic organisms alone.

The acute lowest effect levels for freshwater and marine species are 9.4 E+2 ug/1, respectively. Chronic levels for freshwater species are 3.0 E+0 ug/1. These values are for the general class of phthalate esters and not specifically for DBF (U.S. EPA, 1980).

TECHNICAL PROFILE

DI-N-OCTYLPHTHALATE

Classification

Not classified for carcinogenicity by U.S. EPA.

Oral Exposure

No information is available.

Inhalation Exposure

No information is available.

Toxicity to Human Health and Animals

No information is available for di-n-octylphthalate. As a group, the phthalic acid esters are oily liquids used as intermediates in manufacturing or as lubricants. They are generally toxic in high concentrations and some are considered to be carcinogenic.

TECHNICAL PROFILE

FLUORANTHENE

Fluoranthene is one of the polycyclic aromatic hydrocarbon (PAH) compounds. Because it is formed when gasoline, garbage, or any animal or plant material burns, it is usually found in smoke and soot. This chemical combines with dust particles in the air and is carried into water and onto soil and crops. Fluoranthene is found in coal tar pitch used by industry as an adhesive.

People may be exposed to fluoranthene from environmental sources such as air, water, and from tobacco smoke and overcooked food. Typical exposures are not usually to chrysene alone, but to mixtures of similar compounds.

Classification

The USEPA weight-of-evidence classification for fluoranthene is D, not classifiable as to human carcinogenicity on the basis of no human data and inadequate data from animal bioassays.

Oral Exposure

In a 13 week mouse oral subchronic toxicity study where mice were gavaged with a range of doses of fluoranthene, all treated mice exhibited nephropathy, increased salivation, and increased liver enzyme levels and increased liver weights in a dose-dependent manner. Microscopic liver lesions (indicated by pigmentation) were observed in 65 and 87.5% of the mid- and high-dose mice, respectively. Based on increased SGPT levels, kidney and liver pathology, and clinical and hematological changes, the LOAEL is considered to be 250 mg/kg/day, and the NOAEL is 125 mg/kg/day.

Inhalation Exposure

No inhalation studies were located.

Toxicity to Human Health and Animals

The 1990 Drinking Water Criteria Document for Polycyclic Aromatic Hydrocarbons has received Agency and external review.

TECHNICAL PROFILE

FLUORENE

Fluorene is one of the polycyclic aromatic hydrocarbon (PAH) compounds. Because it is formed when fossil fuels, garbage, or any other plant or animal material is burned, it is usually found in smoke and soot. This chemical combines with dust particles in the air and is carried into water and onto soil and crops. Fluorene is found in coal tar pitch used by industry as an adhesive.

Although there are no human data that specifically link exposure to fluorene with human cancers, it is a component of mixtures that have been associated with human cancer. These include coal tar, soots, coke oven emissions, over cooked food and tobacco smoke.

Classification

USEPA weight-of-evidence classification for fluorene is D, not classifiable as to human carcinogenicity based upon no human data and inadequate data from animal bioassays.

Oral Exposure

Mice were exposed to fluorene suspended in corn oil by gavage for 13 weeks. Increased salivation, hypoactivity, and urine-wet abdomens in males were observed in all treated animals. The percentage of mice exhibiting hypoactivity was dose-related. Labored respiration, ptosis (drooping eyelids), and unkempt appearance were also observed. A significant decrease in red blood cell count, packed cell volume, and hemoglobin concentration was observed. Increased total serum bilirubin levels were also observed. A dose-related increase in relative liver weight was observed in treated mice. A significant increase in absolute and relative spleen and kidney weight was observed in mice exposed to fluorene. Increases in the absolute and relative liver and spleen weights in high-dose males and females were accompanied by histopathological increases in the amounts of hemosiderin in the spleen and in the Kupffer cells of the liver. No other histopathological lesions were observed.

Inhalation Exposure

Not available at this time.

Toxicity to Human Health and Animals

Studies of fluorene for complete carcinogenic activity, inititating activity or co-carcinogenicity with 3-methylcholanthrene in mouse skin painting assays were not positive or were inconclusive.

The 1990 Drinking Water Criteria Document for Polycyclic Aromatic Hydrocarbons has received Agency and external review,

TECHNICAL PROFILE

HEXACHLOROBENZENE

Classification

Hexachlorobenzene, CSC1S (HCB) is a solid, formulated and manufactured from agricultural processes.

The Chronic Health Hazard Assessment for Non-Carcinogenic effects (IRIS, 1989) denotes the EPA is evaluating this substance for a potential human carcinogenicity. It is presently classified as a B2 carcinogen (IRIS, 1990).

Health Effects

HCB is an experimental neoplastigen, potential carcinogen, tumorigen, and teratogen. This chemical can be inhaled, ingested, and irritate the skin and eyes. HCB levels up to 23 ppb in blood are believed to contribute to enzyme disruptions. The mortality of breast fed infants and the epidemic of skin sores and skin discoloration were symptoms denoted upon consumption of HCB. Clinical studies include weight loss, enlargement of the thyroid lymph nodes, skin photosensitization; and abnormal growth of body hair.

Oral Exposure

Reference doses for chronic oral exposure were estimated to be 8 E-l mg/kg/day at the no observed adverse-effect level (NOAEL) and 0.29 mg/kg/day at the lowest observed adverse-effect level (LOAEL), respectively. These doses were based on actual food consumption and body weights provided in a long-term toxicity study of HCB (Arnold, 1985). A 130-week study involved feeding male and female Sprague-Dawley rats HCB for 90 days prior to mating and 21 days after parturition. Animals exposed to HCB and metabolites in vitro produced no adverse effects, although periportal glycogen depletion, peribiliary lymphocylosis, and peribiliary fibrosis were evident. These are not, however, considered induced adverse effects (Arnold, 1985). At higher HCB concentrations, pup mortality, hepatic centrilobular, basophilic chromogenesis, and severe chronic nephrosis can occur.

The toxicity of long-term exposure to humans to HCB was demonstrated by the epidemic of porphyria cutania tarda (PCT) (Peters, 1982). Ninety-five percent mortality and peak sores were observed in children. PCT-associated symptoms include skin lesions, hypertrichosis, and

hyperpigmentation. The exposure caused neurotoxicity and liver damage. Follow-up studies reported PCT symptoms, reduced growth, and arthritic changes to persons who were directly or indirectly exposed. Kuiper-Goodman (1977) performed a subchronic study relating to dose and concentration of HCB. An apparent NOEL of .5 mg/kg/day was concluded. Liver porphyrin and centrilobular hepatocytes were increased along with depletion of heptocellular marker enzymes with highest HCB concentration doses. Liver to body weight ratios were increased as well as porphyrin levels in the kidney and spleen. Highest dose resulted in decrease survival in females, splenomegaly in females, increases in spleen to body and kidney to body weight ratios in males and females. A high confidence level is due to the extensive number of quality research.

Inhalation Exposure

The reference dose for chronic inhalation exposure is not available at this time (IRIS, 1990), and the ACGIH has no suggested standards.

Carcinogenicity to Human Health and Animals

An extensive number of animal studies have been conducted on HCB including reproductive, teratology, and carcinogenicity studies. HCB is classified as a type B2 carcinogen with slope factors of 1.7 E+0 for both oral and inhalation exposures.

TECHNICAL PROFILE

INDENO(1,2,3-C,D)PYRENE

Indeno(l,2,3-c,d)pyrene is one of the polycyclic aromatic hydrocarbon (PAH) compounds. Because it is formed when fossil fuels, garbage, or any other plant or animal material is burned, it is usually found in smoke and soot. This chemical combines with dust particles in the air and is carried into water and onto soil and crops. Indeno(1,2,3-c,d)pyrene is found in coal tar pitch used by industry as an adhesive.

There are animal data that specifically link exposure to indeno(1,2,3-c,d)pyrene with human cancers. It produced tumors in mice following lung implants, subcutaneous injection and dermal exposure. Indeno(l,2,3-c,d)pyrene is a component of mixtures that have been associated with human cancer. These include coal tar, soots, coke oven emissions, over cooked food and tobacco smoke.

Classification

The USEPA weight-of-evidence classification for indeno(l,2,3-c,d)pyrene is B2, probable human carcinogen based upon no human data and sufficient data from animal bioassays. Indeno[l,2,3-c,d]pyrene produced tumors in mice following lung implants, subcutaneous injection and dermal exposure. IndenoL1,2,3-cdlpyrene tested positive in bacterial gene mutation assays.

Oral Exposure

No studies indicating acute or chronic effects of oral exposure were found.

Inhalation Exposure

No studies were found.

Toxicity to Human Health and Animals

In carcinogen bioassays in mice and rats indeno[l,2,3-cd]pyrene exposure resulted in increased incidences of epidermoid carcinomas in a lung implantation study, injection site sarcomas in a subcutaneous injection assay, and skin tumors in dermal application studies.

TECHNICAL PROFILE

2-METHYLNAPHTHALENE

2-Methylnaphthalene is a polycyclic aromatic hydrocarbon compound (PAH). It is formed when fossil fuels, garbage, or any plant or animal material is burned, and, therefore, it is usually found in smoke and soot. 2-methylnaphthalene is found in cigarette smoke, power plant emissions, and coal tar pitch.

Classification

Although not classified by U.S. EPA, 2-methylnaphthalene is structurally similar to non-carcinogen PAH compounds.

Oral Exposure

No information on the pure form is available.

Inhalation Exposure

No information on the pure form is available.

Toxicity to Human Health and Animals

2-methylnaphthalene is a component of PAH mixtures that occur in coal tar, tobacco smoke, and emissions from power plants and foundaries. Although specific information on 2-methylnaphthalene is not available, these mixtures have toxicological effects including death, cancer, and reproductive failure.

TECHNICAL PROFILE

4-METHYLPHENOL

Health Effects

4-Methylphenol (p-Cresol), (C7HgO), is a toxic germicide. Cresols are poisonous, and 8 grams or more taken orally can produce rapid circulatory collapse and death. Chronic poisoning from oral or percantaneous absorption may produce digestive disturbances, nervous disorders, and vertigo. Cresol is moderately toxic by ingestion and inhalation. The main hazard accompanying its use lies in severe chemical burns and dermatitis. It is slightly explosive in the form of vapor when exposed to heat or flame.

Classification

Cresol is being evaluated as a human carcinogen. The evaluation of this chemical is under review by the International Agency for Research on Cancer (IARC) and EPA agencies. Nc$ classification has been assigned to cresol to date.

Oral Exposure

An oral reference dose has been established for 5 E-3 mg/kg/day at the no observed adverse effect level (NOAEL). The lowest observed adverse effect level (LOAEL) is established at 150 mg/kg/day. Subchronic and neurotoxicity studies have been conducted (U.S. EPA 1986) to evaluate several parameters: body and organ weight rates, food consumption, mortality, toxicity signs, and clinical pathology. At the highest dose level of 600 mg/kg/day, a significant reduction in weight was observed (15% for females, 25% males), reduced food consumption, incidence of central nervous system (CNS) signs, as lethary, excessive salivation, tremors, and diarrhea. The liver to body weight and kidney to body weight ratios were significantly increased. Greater prevalence to tracheal epithelial metoplasia is noted. Neurotoxicity studies (U.S. EPA 1987) denoted higher doses of p-cresol (600 mg/kg/day) produced significant neurological events, such as increased salivation, urination, tremors, lacrimation palpebral closure, and rapid respiration. High dosed animals also showed abnormal patterns in neurobehavioral tests. The oral reference dose was calculated to be 0.05 mg/kg/day.

Inhalation Exposure

No reference dose for chronic inhalation exposure is available at this time. Subchronic inhalation studies (Uzhdavine et al. (1972), NIOSH, (1978) recommended a TLV-TWA of 10 tng/m3 or 0.05 mg/kg/day. No effects were seen in guinea pigs, although hematopoietic effects, respiratory tract irritation, and sclerosis of lungs were evidenced in rats.

Toxicity to Human Health and Animals

No health hazard assessments are available for exposed durations at this time. No drinking water reference or ambient water quality criteria for aquatic species and human health have been evaluated (IRIS, 1990).

TECHNICAL PROFILE

NAPHTHALENE

Naphthalene is one of the polycyclic aromatic hydrocarbon (PAH) compounds. Because it is formed when gasoline, garbage, or any animal or plant material burns, it is usually found in smoke and soot. This chemical combines with dust particles in the air and is carried into water and soil and onto crops. Naphthalene is found in coal tar pitch used by industry as an adhesive.

People may be exposed to naphthalene from environmental sources such as air, water, and soil, and from cigarette smoke and overcooked food. Typical exposures are not usually to naphthalene alone, but to a mixture of similar chemicals.

Classification

USEPA Weight-of-evidence classification— D; not classifiable as to human carcinogenicity on the basis that no human data and inadequate data from animal bioassays exist.

Oral Exposure

A group of 28 rats was exposed to a diet supplemented with naphthalene, 6 times/week. Treatment was stopped when total dose was 10 g/rat. The average daily dose was approximately 10 to 20 mg/day (approximately 30 to 60 mg/kg/day). Tumors were evaluated in animals that died spontaneously at about 700 to 800 days of age. No carcinogenic responses were reported.

On intraperitoneal administration in rats (species/number/sex unspecified), naphthalene was more toxic than acenaphthene and acenaphthylene. Two LD/50 values were reported, but it is unclear to which of the three chemicals these values belonged.

Inhalation Exposure

In a short-term pulmonary tumor bioassay, Adkins et al. (1986) exposed groups of 30 female A/J strain mice by inhalation to 0, 10, or 30 ppm naphthalene for 6 hours/day, 5 days/week for 6 months. While naphthalene caused a statistically significant increase in the number of adenomas per mouse lung, there was no apparent dose-response. This assay is considered to be a short-term, in vivo, lung tumor assay.

Intraperitoneal and intratracheal administration of naphthalene, acenaphthene, and acenaphthylene produced monotypic effects in the form of vascular disorders, and degeneration in the internal organs and central nervous

system. Inflammatory changes were also observed in the lungs; the degree was the same for all three substances. Splenic degeneration was noted among the unscheduled deaths in this study. It was concluded that chronic inhalation of acenaphthene and acenaphthylene had more pronounced toxic effects than naphthalene.

Toxicity to Human Health and Animals

U.S. EPA. 1990. Drinking Water Criteria Document for Polycyclic Aromatic Hydrocarbons (PAHs). Prepared by the Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH for the Office of Drinking Water, Washington, DC. Final Draft. ECAO-CIN-D010, September, 1990.

TECHNICAL PROFILE

N-NITROSQDIPHENYLAMINE

N-nitrosodiphenylamine is structurally related to carcinogenic nitrosamines.

Human exposure to nitrosamines results from contact with mixtures containing these compounds (e.g., cutting oils, tobacco products). Because of potential confounding by the other substances in these mixtures, data are of limited use in the evaluation of carcinogenicity of individual nitrosamines.

Classification

The USEPA weight-of-evidence classification for n-nitrosodiphenylamine is B2, probable human carcinogen based upon increased incidence of bladder tumors in male and female rats, reticulum cell sarcomas in mice, and structural relationship to carcinogenic nitrosamines.

Oral Exposure

N-nitrosodiphenylamine in diet to groups rats. Dose-related mortality was noted in females. Statistically increased incidence of urinary bladder transitional cell carcinomas was observed in both sexes. Epithelial hyperplasia and squamous metaplasia also occurred, as did integumentary fibromas in males.

Inhalation Exposure

Quantifiable information on toxicity of n-nitrosodiphenylamine in its pure form is not available.

Toxicity to Human Health and to Animals

Nitrosodiphenylamine has produced mixed responses in genetic toxicology tests. Adequate numbers of animals were treated and observed for their lifetime. Significant increases in tumor incidence were observed only in highdose animals.

TECHNICAL PROFILE

PHENANTHRENE

Phenanthrene is one of the polycyclic aromatic hydrocarbon (PAH) compounds. Because it is formed when gasoline, garbage, or any animal or plant material burns, it is usually found in smoke and soot. This chemical combines with dust particles in the air and is carried into water and onto soil and crops. Phenanthrene is found in coal tar pitch used by industry as an adhesive.

People may be exposed to phenanthrene from environmental sources such as air, water, and soil, and from cigarette smoke and overcooked food. Typical exposures are not usually to phenanthrene alone, but to a mixture of similar chemicals.

Classification

The weight-of-evidence classification for phenanthrene is D, not classifiable as to human carcinogenicity on the basis that no human data and inadequate data from a single gavage study in rats and skin painting and injection studies in mice exists

Oral Exposure

No adequate information exists on acute or chronic effects from oral exposure to phenanthrene.

Inhalation Exposure

No adequate information exists on acute or chronic effects from inhalation exposure to phenanthrene.

Toxicity to Human Health and Animals

Data from a rat gavage study and mouse skin application and injection studies are not adequate to assess the carcinogenicity of phenanthrene. Current theories regarding the mechanisms of metabolic activation of polycyclic aromatic hydrocarbons lead to predictions of a carcinogenic potential for phenanthrene. Phenanthrene may have a "bay-region" structure. It is metabolized by mixed function oxidases to reactive diol epoxides that have been shown to be weakly mutagenic in some bacterial and mammalian cell assays. Evidence from in vivo assays indicates, however, that phenanthrene metabolites have a relatively low tumorigenic potential. While some studies have considered phenanthrene to have a "bay- region" structure, it may not clearly fall into this category.

The 1990 Drinking Water Criteria Document for Polycyclic Aromatic Hydrocarbons (PAHs) has received Agency and external review.

TECHNICAL PROFILE

PYRENE

Pyrene is absorbed by the skin and is a skin irritant. Workers exposed to 3 to 5 mg/m3 of pyrene exhibited some teratogenic effects. Pyrene is a polycyclic aromatic hydrocarbon (PAH). The acute toxicity of pure PAHs appears low when administered orally or dermally to rats or mice. Human exposure to PAHs is almost exclusively via the gastrointestinal and respiratory tracts, and approximately 99 percent is ingested in the diet. Despite the high concentrations of pyrene to which humans may be exposed through food, there is currently little information available to implicate diet-derived PAHs as the cause of serious health effects.

Classification

The USEPA weight-of-evidence classification for pyrene is D, not classifiable as to human carcinogenicity on the basis of no human data and inadequate data from animal bioassays.

Oral Exposure

Mice dosed with pyrene via gavage exibited nephropathy, characterized by the presence of multiple foci of renal tubular regeneration, often accompanied by interstitial lymphocytic infiltrates and/or foci of interstitial fibrosis. The kidney lesions were described as minimal or mild in all dose groups. Relative and absolute kidney weights were reduced in the two higher dosage groups. Based on the results of this study, the low dose (75 mg/kg/day) was considered the NOAEL and 125 mg/kg/day the LOAEL for nephropathy and decreased kidney weights.

In another study of rats fed a diet containing pyrene, reported food intake was normal while body weight gain decreased relative to controls. Also observed was enlargement of livers and increased hepatic lipid content in animals treated with pyrene.

Inhalation Exposure

There are no adequate studies of inhalation exposure available for pyrene.

Toxicity to Human Health and Animals

U.S. EPA. 1990. Drinking Water Criteria Document for Polycyclic Aromatic Hydrocarbons (PAHs). Prepared by the

Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH for the Office of Drinking Water, Washington, DC. ECAO-CIN-D010, September, 1990. (Final Draft)

Furans/Dioxins

TECHNICAL PROFILE

DIOXINS/FURANS

Human and animal data indicate that 2,3,7,8-TCDD can be absorbed following ingestion, and although bioavailability is affected by binding to soils, the extent of absorption is only decreased by approximately 50%. In addition, animal data indicate that 2,3,7,8-TCDD may be absorbed well through the skin depending on such variables as the dose or the material to which 2,3,7,8-TCDD is absorbed. Following absorption, 2,3,7,8-TCDD is distributed to tissues in proportion to the lipid content. 2,3,7,8-TCDD can cross the placenta with subsequent exposure of the fetus, and the newborn can be exposed following redistribution of 2,3,7,8-TCDD during lactation. Metabolism of 2,3,7,8-TCDD is currently thought to result primarily in detoxification and relatively rapid removal of the metabolites through excretion in the bile and urine. Unmethabolized 2,3,7,8-TCDD is also excreted through direct intestinal elimination in feces as well as through lactation. There are species and strain differences in both metabolism and elimination rates, with elimination half-lives varying from 11 days in the hamster, which is relatively resistant to 2,3,7,8-TCDD toxicity, to >1 year in the monkey, which is sensitive to the toxicity of 2,3,7,8-TCDD. There is, however, no clear correlation between toxicity and the elimination half-life for 2,3,7,8-TCDD.

Although humans have been exposed to 2,3,7,8-TCDD as a contaminant of herbicides and industrial chemicals, there have been no reported deaths from acute exposure. Lethal oral doses of 2,3,7,8-TCDD vary from 0.6 to 5,000 pg/kg for guinea pigs and hamsters, respectively, with other species tested having LDSO values between these two extremes. Subchronic LDSO values for cumulative (total) exposure during a 90-day oral study w th guinea pigs were essentially the same as those observed after acute exposure. A 9-month feeding study of a small number of monkeys indicated that a dose of 2 to 3 ng/kg resulted in death. The acute dermal LDSO value for 2,3,7,8-TCDD in rabbits has been reported to be 275 pg/kg; however, no other species have been tested, and rabbits are only intermediate in sensitivity to 2,3,7,8-TCDD in oral toxicity studies. Inhalation experiments have not been conducted.

The only effect clearly demonstrated to be produced in humans following 2,3,7,8-TCDD exposure is' chloracne. This lesion is a systemic toxic effect and not solely a dermal effect. Although animal models are available to study chloracne, there are limitations in investigating this

toxicological end point. The lestions produced in animals are different from the lesions in humans, and the expression of this lesion may be limited to monkeys, specific strains of mice, and rabbits (observed only on the ears after dermal application).

Exposure to 2,3,7,8-TCDD in the environment is never to 2,3,7,8-TCDD alone but to materials such as incinerator fly ash or industrial wastes, which contain 2,3,7,8-TCDD along with many other congeners of PCDDs, as well as other potentially toxic materials. The EPA has recognized the public and toxicological concerns resulting from exposure to these compounds, as well as the gaps in available information with which to evaluate the human health potential from exposure (EPA 1987). In response to this problem, the EPA Chlorinated dibenzo-p-dioxins/Chlorinated dibenzofurans Technical Panel of the Risk Assessment Forum has developed and recommended an interim method for assisting in estimating the risk from exposure to these chemical mixtures that can be used until the data gaps are filled. This procedure generates the "2,3,7,8-TCDD equivalence factors" (TEFs) of complex mixtures of chlorinated dibenzo-p-dioxins and dibenzofurans based on congener- and isomer-specific data. The TEFs presented below are relative values and are a means of relating toxicity data for other chlorinated dibenzo-p-dioxins and dibenzofurans to an equivalent level of 2,3,7,8-TCDD, The TEF for 2,3,7,8-TCDD is defined as unity, whereas all other TEFS are unity or less, thus reflecting the lower toxic potency of most PCDD congeners.

Pesticides/PC Bs

TECHNICAL PROFILE

4,4' ODD

4,4' DDD, Ci4Hi2,Cl4, is a colorless crystalline compound used in the formation and application of insecticides.

Classification

Weight of evidence classification for 4,4' DDD is B2: a probable human carcinogen based on an increased evidence of lung, liver, and thyroid tumors in animal studies. 4,4' DDD is structurally similar to DDT, which is also a probable human carcinogen.

Health Effect

Some DDD exists with carcinogenic evidence present. No acute or chronic systems are noted to detect the presence of DDD.

Oral Exposure

No human epidemiological data are available for DDD. Autopsy studies relating tissue levels of DDT to cancer incidences have yielded conflicting results. These studies reported levels of DDT, and 4,4' DDD levels were higher in cancer victims than in those dying of other diseases (Casarett et al., 1968). Other studies did not relate this relationship (Naier-Bode). Studies were of insufficient duration to determine carcinogenicity of DDT in humans.

Tomatis' (1973) animal studies, however, showed a significant increase in incidences of lung tumors seen in both sexes. In males, a significant increase in liver tumors was also seen.

An increased incidence of hepatocellular carcinomas was seen in both sexes by comparison to controls, but the increase was not statistically significant. Another study by NCI (1978) observed increased incidences of thyroid tumors. This increased incidence was not statistically significant by comparison to concurrent controls. Tumor incidence did not appear to be dose-related. Pathologists and statistical results suggest possible carcinogenic effects in male rats. A definitive interpretation was not possible (NCI, 1978). 4,4' DDD is structurally similar to DDT (Petterson and Robinson, 1964). Positive effects were found with DDD in mammalian cytogenetic assays and host mediated assay (ICPEMC, 1984). An oral risk estimate of

2.4E-1 mg/kg/day and an associated drinking water unit risk of 6.9 E-6 |ug/l have been calculated.

TECHNICAL PROFILE

4,4'-DDE

4,4'-DDE, Ci8H20Cl2, is similar to DDT. It is the principal breakdown of DDT and is used as an insecticide and has moderate persistence in the soil.

Classification

The U.S. EPA weight of evidence classification for DDE is Group B2: a probable human carcinogen. This classification is based on an increased incidence of liver tumors, including carcinomas in two strains of mice, in hamsters and of thyroid tumors in female rats by diet.

Health Effects

Health effects are similar to those effects found by DDT exposure. DDE, like DDT, can be inhaled, absorbed through the skin, ingested, or irritate the eyes and skin. It is moderately an acute toxic to man and organisms. Major concerns are related to its chronic effects (Sittig, 1985). Symptoms include paresthesia of tongue, lips and face; tremors; apprehension, dizziness, confusion, malaise, headaches, convulsions; paresis of the hands; vomiting; and irritation of the eyes and skin.

Oral Exposure

Human epidemiological data are not available for DDE. Evidence for the carcinogenicity in humans of DDT, a structural analog, is based on autopsy studies relating tissue levels of DDT to cancer incidence. DDT and DDE tissue levels were higher in cancer victims than those dying of other diseases (Casarett, 1968).

Animal carcinogenicity data are sufficient. A dose-dependent and statistically significant increase in incidence of hepatocellular carcinomas was observed in males and females in comparison with controls. A study performed administered 250 ppm DDE in feed for a lifetime identified incidences of hepatomas in both males and females (Tomatis, 1974). An increase in the incidence of neoplastic modules of the liver was observed in both sexes in comparison with vehicle-treated controls (Rossi,). A dose-dependent trend in incidence of thyroid tumors was observed in females, which was statistically significant by the Cochran Armitage.

DDE was mutagenic in mouse lymphoma (L5178Y) cells and Chinese hamster (V79) cells, but not in Salmonella (ICPEMC, 1984). DDE is structurally similar to and a metabolite of DDT (Peterson and Robinson, 1964). The oral slope factor is calculated to be 3.4E-1 (mg/kg/day)"'.

Inhalation Exposure

The quantitative estimate of carcinogenic risk from inhalation exposure is not available (IRIS, 1990). Values for 4,4' DDT are, therefore, used.

Toxicity to Human Health and Animals

Limits to protect human health and aquatic organisms are similar to levels established for DDT. To protect human health, an estimate of preferrably zero, due to carcinogenic potential, was established.

To protect freshwater aquatic organisms, a level of 1. OE-3 jag/1 as a 24-hour average was calculated. To protect saltwater, 1.OE-3 jag/1 was calculated.

TECHNICAL PROFILE

4,4'-DDT

Historically, DDT was released to the environment during its formulation and extensive use as a pesticide in agricultural and vector control applications. Although it was banned for use in this country in 1972, it is still being used in several areas of the world. DDT, DDE, and ODD in the atmosphere are subject to photodegradation or redeposition by rain or dry deposition. DDT and its environmental degradation products preferentially bind to soil and sediment, where they may be subject to photodegradation on the surface and biodegradation in the subsurface. However, under certain conditions, DDT may persist for long periods of time or may be converted to DDE, which persists even longer. DDT, DDE, and ODD in water are subject to sedimentation, volatilization, photodegradation, and uptake into the food chain. Both DDT and DDE bioaccumulate in organisms, and levels are subject to increase as they advance up the food chain. DDT and its metabolites have been detected in virtually all media. Human exposure i-n this country results primarily from ingestion of meat, fish, poultry, and root and leafy vegetables. The oral RfD for DDT is 5x10"4

mg/kg/day.

DDT is probably one of the best known and most widely studied pesticides. DDT was used extensively during World War II in control of lice and other insects by application directly to humans. Numerous studies have been conducted in a variety of species. The human data are somewhat more limited. The central nervous system (CNS) is a major target organ in humans and animals, while the liver is a major target organ in animals.

In experimental animals, liver effects, ranging from increased enzyme levels to necrosis and tumors, and neurological effects, including myoclonus, appear to be the primary effects associated with DDT and DDE exposure. Reproductive effects have also been reported. Adrenal toxicity, advancing to necrosis, appears to be the primary effect associated with ODD exposure in animals.

Studies in workers in DDT manufacturing plants or spray applicators who had occupational expsoure to DDT over an extended period provide information on the possible adverse effects on human health. Occupational exposure to DDT involved multiple routes of exposure. The primary contact was probably inhalation and dermal; however, absorption of DDT from the lungs may not have been significant, and ingestion due to the mucociliary

apparatus of the upper respiratory tract is most likely. Therefore, occupational exposures cannot be assigned a single route. In addition, there are no experimental studies in animals by the inhalation route with which to compare observed human effects. Some of the CNS effects observed in animals by the oral route have also been identified in humans exposed occupationally or through voluntary or accidental ingestion of DDT. These effects include cold moist skin, hypersensitivity to contact, tremor, and convulsion.

EPA (1988a) has estimated an oral potency factor of 3.4X10"1 (mg/kg/day)"'. This potency factor is derived from the geometric mean of potency factors based on the incidence of liver tumors in mice and rats as reported by Cabral et al. (1982b), Rossi et al. (1977), Terracini et al. (1973) Thorpe and Walker (1973), Tomatis and Turusov (1975), and Turusov et al. (1973). At this potency factor, the lifetime average daily dose that would result in risk ranging from IxlO"4 to IxlO"7 is 2,9x10"4 mg/kg/day. DDT is a B-2 carcinogen.

TECHNICAL PROFILE

AROCLOR-1260, AROCLOR-1254, AROCLQR-1242 (PCBs)

Polychlorinated biphenyls (PCBs), Ci 2 H t 0 - xCl x , are complex mixtures containing isomers of chlorobiphenyls with different chlorine content. There are 209 possible compounds obtainable by substituting chlorine for hydrogen on different positions of the biphenyl ring system. It should also be noted that PCB commercial mixtures have been shown to contain other classes of chlorinated derivatives. PCBs are used in electrical capacitors, electrical transformers, vacuum pumps, and gas-transmission pumps (Merck, 1983). They are also used in hydraulic fluids, plasticizers, adhesives, fire retardants, wax extenders, inks, lubricants, and oils.

Classification

PCB and its compounds have been classified in Group B2 by the U.S. EPA: a probable human carcinogen based an hepatocellular carcinomas in animal studies and inadequate yet suggestive evidence of excess risk of liver cancer in humans by ingestion and inhalation or dermal contact.

Health Effects

PCBs can be inhaled, ingested, and absorbed through the skin. Toxic effects in humans include chloracne, pigmentation of skin and nails, excessive eye discharge, swelling of eyelids, distinctive hair follicles, and gastrointestinal disturbances (Merck, 1983). Generally, toxic effects are dependent on the degree of chlorination, the higher degree of chlorination, the stronger the effects.

Acute and chronic exposure can cause liver damage. Signs and symptoms include edema, jaundice, vomiting, anorexia, nausea, fatigue, and abdominal pains. Studies of oral intake indicate that chlorinated diphenyls are embryotoxic, causing stillbirths and increased eye discharges in infants born to women exposed during pregnancy (Sittig, 1985).

Oral Exposure

Although there are many human carcinogenic studies, most of the data has been evaluated as inadequate due to confounding exposures or lack of exposure quantification. Bahn's studies (1976, 1977) at a petrochemical plant researched and documented carcinogenicity associated with PCB exposure. An increase in malignant melanomas was

reported, but data were inadequate due to lack of exposure and other potentially known carcinogens. NIOSH (1977) concurred with Bahn's findings. Brown & Jones (1981) reported no excess risk of cancer to employees at capacitor manufacturing plants. Brown's report (1987) reported statistically excessive risk of liver and biliary cancer. In 1980, the use of PCBs was abandoned. Bertozzi et al. (1987) conducted a mortality study of workers at a capacitor plant, and through these studies noted the number of deaths from malignant tumors to be significantly higher. Deaths from hematologic neoplasms in males were higher, and deaths to females with cancer were also higher.

A 16-year mortality study was conducted in relation to PCB-contantinated rice (Amano, 1984). A high risk of liver cancer in males and females was observed. This study lacked clarification of health effects seen in Yusho victims due to ingestion of polychlorinted dibenzofurans rather than to PCBs themselves (EPA, 1988).

A long-term bioassay of Aroclor 1260 (Kimbrough, 1975) produced heptocellular carcinomas in female Sherman rats when 100 ppm was administered for 630 days to 200 animals. Hepatocellular carcinomas and neoplastic nodules were also observed. Carcinomas of the gastrointestinal tract were observed among treated animals (NCI, 1978), and an apparent dose-related incidence of hepatic nodular hyperplasia in both sexes as well as hepatocellular carcinomas were also observed. In studies conducted by Norback and Weltman (1985), females exhibited a 91 percent incidence of heptocellular carcinoma. Concurrent liver morphology studies showed sequential progression of liver lesions to heptocellular carcinomas.

Most genotoxicity data of PCBs have been negative. Cogeners showed no evidence of mutagenic effects, and Peakall (1972) reported results showing a possible clastogenic action of PCBs in dove embryos. An oral slope factor for a quantitative estimate of risk from oral exposure is calculated to be 7.7 mg/kg/day'1 with a drinking water risk unit of 2.2 E-4 ng/1. Human dosage assumes a time weighted average (TWA) daily dose of 3.45 mg/kg/day.

Inhalation Exposure

No quantitative estimate has been established for carcinogenic risks from inhalation exposure (IRIS, 1990). The federal standards (NIOSH) recommended a level of 1.0 ug/m1 on a 10-hour TWA basis (Sittig, 1985).

Toxicity to Human Health and Animals

A value of zero was preferred to protect human life. To protect freshwater aquatic life, .014 ng/1 was calculated as a 24 TWA. To protect saltwater aquatic life, a value of .030 ng/1 is preferred (Sittig, 1985).

TECHNICAL PROFILE

ENDOSULFAN

Endosulfan is used as an insecticide for vegetable crops, fruits, and nuts. Endosulfan is very toxic. Exposure can cause death. Symptoms include gagging, vomiting, diarrhea, agitation, convulsions, foaming at the mouth, dyspnea, apnea, bluing of skin and loss of consciousness.

Classification

This chemical has not been evaluated by the USEPA for evidence of human carcinogenic potential.

Oral Exposure

Rats were fed endosulfan starting at 6 weeks of age. Yellowish discoloration of cells in the proximal convoluted tubules of the kidney were seen in males. In addition, granular clumped pigment was observed in trace amounts in these cells. Low hemoglobin in females and elevated platelet counts in males was also observed.

Inhalation Exposure

Not available at this time.

Toxicity to Human Health and Animals

AMBIENT WATER QUALITY CRITERIA

Human Health

Water and Fish Consumption — 7.4E+1 ug/L Fish Consumption Only — 1.59E+2 ug/L

Ag_uatic Organisms

Freshwater:

Acute —Chronic —

2.2E-1 ug/L 5.6E-2 ug/L

(at any time) (24 hour average)

Marine:

Acute —Chronic —

3.4E-2 ug/L 8.7E-3 ug/L

(at any time) (24 hour average)

TECHNICAL PROFILE

ALUMINUM

Aluminum is a common element of the natural environment comprising up to 10 percent of the content of soil and stone. Aluminum is generally not toxic to animals. Solubility increases at low pH and in acidic waters, such as bogs, aluminum concentrations can reach levels toxic to fish.

Classification

U.S. EPA classifies aluminum as E, a non-carcinogen.

Oral Exposure

No data indicate toxicity to aluminum.

Inhalation Exposure

No information is available at this time.

Toxicity to Human Health and Animals

There is no available toxicological information for mammals. Aluminum is toxic to fish at elevated concentrations.

TECHNICAL PROFILE

ANTIMONY

Antimony, Sb, is a silver-white, lustrous, hard, brittle metal. It does not tarnish in dry air and only slowly in moist air. It is used in the manufacture of alloys, such as Britannia or Babbitt metal; in fireworks; for thermoelectric piles; and coating metals. A highly toxic gas, stibine, may be released from the metal under certain conditions (Merck, 1985).

Classification

This chemical has not been evaluated by the U.S. EPA for evidence of human carcinogenic potential.

Health Effect

Most antimony compounds are poisons by ingest ion, inhalation, and intraperitoneal routes (Sax/Lewis, 1987). Antimony and its compounds are generally regarded as primary skin irritants. Lesions generally appear on exposed moist areas of the body, but rarely on the face. The dust and fumes are also irritants to the eyes, nose, and throat, and may be associated with gingivitis, anemia, and ulceration of the nasal septum and larynx. Antimony trioxide causes a dermatitis known as "antimony spots." This form of dermatitis results in intense itching followed by skin eruptions. A diffuse erythemia may occur, but usually the early lesions are small papules. They may enlarge and become pustular (Sittig, 1985). Antimony and its compounds have been reported to cause dermatitis, keratitis, conjunctivitis, and nasal septal ulceration by contact fumes or dust. Conditions should be made to avoid contract with hydrogen. Stibine, a toxic substance, causes symptoms of nausea, vomiting, headache, hemolysis, hematuria, abdominal pain, and death. Stibine can be liberated from storage batteries (Merck, 1985). Liver and kidney degenerative changes are late manifestations.

Antimony compounds are less toxic than antimony. Antimony trisulfide has been noted to cause myocardial changes in man and animal studies. Antimony trichloride and pentachloride are highly toxic and can irritate and corrode the skin. Antimony fluoride is extremely toxic, particularly to pulmonary tissue and skin.

Oral Exposure

An oral reference dose of 4E-4 mg/kg/day was calculated. A life-term study of zerconium, niobium, antimony, vanadium, and leads in rats was conducted (Schroeder, 1970). Growth rates of treated animals were not affected. Nonfasting blood glucose levels were decreased in treated males, and cholesterol levels were altered in both sexes. Only one level of antimony was administered, therefore, a no observed acute effect level (NOAEL) can be calculated. No increase in tumors were seen, and a decrease of mean heart weight was noted in male rats.

A similar study (Kanisawa and Schroeder, 1969) gave potassium antimony tartaate at 0 and 5 ppm for 18 months. Lifespans were significantly reduced in both males and females, yet the degree of antimony toxicity was less severe in mice than rats. Bradley and Fredrick (1941) reported disturbances in glucose and cholesterol metabolism in rats ingesting 5 mg/1 antimony, but no signs of injury to the heart were observed in rats receiving 100 mg/kg/day. Higher doses of antimony trioxide were tolerated by rats in studies by Sunagawa (1981) suggesting an NOAEL of 500 mg/kg, but these studies are of inadequate duration to assess adverse effects on toxicity.

According to the U.S. EPA (1980), multimedia antimony exposures are essentially negligible by comparison to occupational exposures at which discrete clinical health effects have been observed. Myocardial effects are among the best-characterized human health effects associated with antimony exposure. No adequate data, however, exist on oral exposure to antimony, which permits a reasonable estimate of no effect levels regarding heart damage (IRIS, 1989).

Inhalation Exposure

No reference dose for chronic inhalation exposure is available at this time (IRIS, 1989).

Toxicity to Human Health and Animals

The ambient water quality criteria (AWQC) for human health have been calculated to be 1.46E+2jag/l and 4.5E+4ng/l for water and fish consumption, respectively. These AWQC have been calculated for freshwater organisms. To protect freshwater aquatic life, 9E+3pg/l was calculated for acute toxicity, and a value of 1.6E+3ng/l was established for the chronic toxicity level.

TECHNICAL PROFILE

ARSENIC

Arsenic, As, is present as an impurity in many metal ores and is produced as a byproduct in the smelting of these ores, particularly copper. It is labelled as a poison and is used in a variety of industries: agricultural, insecticides, herbicides, Pharmaceuticals, pigment production, and manufacturing of glass.

Classification

This substance and certain arsenic compounds have been listed as carcinogens. The weight of evidence classification as to human carcinogenicity is listed in Group A based on observation of increased lung cancer mortality in populations exposed primarily through inhalation and an increased skin cancer incidence in several populations consuming drinking water with high arsenic concentrations.

Health Effects

Arsenic can be inhaled or ingested through dust and fumes. Acute toxic effects are generally seen following ingest ion of the compound. Symptoms may develop within one-half to four hours following ingestion and are characterized by constriction of the throat followed by dysphagia, epigastric pain, vomiting, and watery diarrhea. If large amounts are ingested, shock may develop due to severe fluid loss, and death may ensue within 24 hours. Exfoliative dermatitis and peripheral neuritis may develop. Acute cases due to inhalation are rare. Chronic arsenic poisoning due to ingestion is also rare. It can, however, be inhaled resulting in symptoms of weight loss, nausea, erruption of the skin, loss of hair, and peripheral neuritis. Horizontal white lines (striations) on the fingernails and toenails are commonly seen in chronic arsenic poisoning. Liver damage from chronic poisoning is still debated. Arsenic does have a depressant effect upon bone marrow, with evidence of also causing lung and skin cancer.

Oral Exposure

Oral reference dose values are given as 1E-3 mg/kg/day (HEAST, 1990). The risk assessment forum concluded that the most appropriate basis for an oral quantitative estimate was the study by Tsey (1977) which reported increased prevalence of skin cancers in humans as a consequence of arsenic exposure in drinking water. Sodium

arsenic transformed Syrian hamster embryo cells (Dipaolo and Casto, 1979) to produce sister-chromatid-exchange in DON cells, CHO cells, and human peripheral lymphocytes exposed in vitro (Wan et al., 1982; Anderson, 1983). Arsenic compounds have not been shown to mutate bacterial strains, but it produces preferential killing of repaired deficient strains (Rossman, 1981).

Inhalation Exposure

The quantitative estimates of carcinogenic risk from inhalation exposure are 5.0 E+l (mg/kg/day)"l and a unit risk of 4.3 E-3 ng/m3. A geometric mean of inhalation data was obtained within distinct exposed populations (U.S. EPA, 1994). The final estimate is the geometric mena of those two values.

It is assumed that the increase in age-specific mortality rate of lung cancer was a function only of cumulative exposure. Exposure assessments observed that lung cancer incidences significantly increased over expected values.

Toxicity to Human Health and Animals

The maximum contaminant level goal (MCLG) for drinking water of .05 mg/1 for arsenic is proposed based on the current MCL of 0.05 mg/1. Even though arsenic is potentially carcinogenic in humans by inhalation and ingestion, its potential essential nutrient value was considered in determination of a MCLG (NAS, 1983).

The ambient water quality criteria (AWQC) for human health are 2.2 E-3 ug/1 and 1.75 E-2 iag/1 for water and fish comsumption, respectively. For aquatic organisms, acute levels for arsenic III are calculated to be 3.6 E+2 ug/1 and 6.9 E+l jag/1 for freshwater and marine organisms, respectively. Likewise, the chronic levels for freshwater and marine organisms are valued at 1.9 E-2 pg/1 and 3.6 E+l pg/1, respectively. Much less data are available on the aspects on arsenic V to aquatic organisms, but the toxicity seems to be less.

TECHNICAL PROFILE

BARIUM

Barium, Ba, an alkaline earth metal, consists of silver-white, slightly lustrous, somewhat malleable metal. It is produced by the reduction of barium oxide. The primary sources are the minerals barite (BaS04) and witherite (BaC03). Barium may ignite spontaneously in air in the presence of moisture involving hydrogen. Most barium compounds are soluble in water, although the chemical itself is not. Metallic barium is used as a carrier for radium and for the removal of residual gas in vacuum tubes and in alloys with nickel, lead, calcium, magnesium, sodium, and lithium. Barium compounds are used in several manufacturing operations: X-ray diagnostic work, glassmaking, papermaking, and animal and vegetable oil refining. They are used in brick and tile, pyrotechnics, and the electronics industries. They are found in lubricants, pesticides, glazes, textile dyes and finishes, Pharmaceuticals, rodenticides, a stabilizer and mold lubricant in the rubber and plastics industries, an extender in paints, a loader for paper, soap, rubber and linoleum, and a fire extinguisher for uranium or plutonium fires.

Classification

This chemical has not been evaluated by the U.S. EPA for evidence of human carcinogenic potential.

Health Effects

The soluble barium salts, such as chloride and sulfide, are poisonous when ingested (Sax/Lewis, 1987). The insoluble sulfate used in radiography is not acutely toxic. Few cases of systemic poisoning have been reported. Barium compounds, when ingested or given orally, exert a profound effect on all muscles and especially smooth muscles, markedly increasing their contractility. The heart rate is slowed and may stop in systole. Other effects are increased intestinal peristalsis, vascular constriction, bladder contraction, and increased voluntary muscle tension. The inhalation of dust of barium sulfate may lead to deposition in the lungs in sufficient guantities to produce "baritosis," a benign pneumoconiosis. Barium and its compounds may affect the heart, lungs, central nervous system, skin, eyes, and respiratory system (Sittig, 1987).

Oral Exposure

The oral reference dose for barium, calculated to be 5E-2 mg/kg/day, may change in the near future pending the outcome of further review now being conducted by the oral reference dose assessment group (IRIS, 1989). The Office of Drinking Water (ODW) believes that no single study considered alone is appropriate to calculate a lifetime reference dose for barium. Brenneman et al. (1981) concluded that there was no statistically significant difference in blood pressure between humans ingesting drinking water containing barium. An epidemiologic study and various rodent studies have been conducted (Schroeder and Kitchener, 1975 a,b; Tardiff, et al.)

Perry et al. (1983) exposed weanling rats to barium at 1,10, or 100 ppm in drinking water for up to 16 months. There were no signs of toxicity at any barium dose level. Systolic blood pressure measurements revealed no increase in pressure in animals exposed to 1 ppm for 16 months, an increase of 4 mm Hg in animals exposed to 10 ppm barium for 16 months and an increase of 16 mm Hg in animals exposed to 100 ppm barium for 16 months. The animals in this study were maintained in a special contaminant-free environment and fed a dirt designed to reduce exposure to trace metals. It is possible that the restricted intake of certain beneficial metals may have preexposed the test animals to the hypertensive effects of barium (U.S EPA, 1985).

Schroeder and Kitchener (1975) exposed rats and mice to 5 mg/1 barium in drinking water for a lifetime. No adverse effects were observed; however, blood pressure was not measured (IRIS, 1989). Tardiff et al. (1980) exposed rats to barium at various concentration levels. Although the barium body burden increased with increasing barium dosage, no conclusive signs of barium toxicity were observed in these animals. Blood pressure was not measured.

A major limitation to these studies is the minimized exposure to trace metals (calcium) in the food, water, and laboratory environment, that they may have contributed to the observed effects. Thus, a lowest observed adverse effect level (LOAEL) identified in the Perry et al. (1983) study has been calculated at 5.1 mg/kg/day.

Inhalation Exposure

A reference dose for chronic inhalation exposure is given as 1E-4 mg/kg/day (HEAST, 1989).

Toxicity to Human Health and Animals

A maximum contaminant level goal (MCLG) for drinking water of 1.5 mg/1 is proposed based on the provisional drinking water equivalent level (DWEL) of 1.8 mg/1. A DWEL was calculated from a LOAEL of 5.1 mg/kg/day for hypotensinogenic and cardiotoxic effects in rats.

No ambient water quality standard for protection of aquatic organisms is established.

TECHNICAL PROFILE

BERYLLIUM

Beryllium, Be, is a gray metal that combines the properties of light weight and high tensile strength. Beryllium is used as a neutron reflector and neutron moderator in nuclear reactors. It is also used in the manufacture of beryllium alloys, namely beryllium copper and beryllium aluminum. Beryllium is also used for radio components, in aerospace structures, and inertial guidance systems.

Classification

The U.S. EPA's weight of evidence classification for human carcinogenicity is Group B2: a probable human carcinogen based on limited evidence from studies in humans and sufficient studies in animals. Beryllium has been shown to induce lung cancer via inhalation in rats and monkeys and to induce osteosarcomas in rabbits via intravenous or intramedullary injection. Human epidemology studies are considered to be inadequate (IRIS, 1989).

Health Effects

Death may result from short exposure to very low concentrations of the element and its salts (Merck, 1983). Contact dermatitis, chemical conjunctivitis, corneal burns, nonhealing ulceration at site of injury, and subcutaneous nodules may occur following exposure. Acute effects include pneumonitis, which may result from single exposure to beryllium disease and may appear in three months to 15 years often after short exposure. The death rate is approximately 25 percent.

Oral Exposure

An oral reference dose has been established at 5E-3 mg/kg/day based on life-time studies in rats where microscopic changes were noted in heart, kidney, liver, and spleen (Shroeder, 1975). Similar studies showed decreased body weight, and a no observed adverse effect level (NOAEL) was calculated to be 0.95 mg/kg/day. This reference is limited to soluble beryllium salts. Data on teratogenicity or reproductive effects of beryllium are limited, but it has been reported to produce embryolethality and terata in chick embryos (Puzanova, et al., 1978). Confidence in this study is rated low, reflecting the need of more toxicity data. No reference dose for chronic inhalation exposure is available at this time.

Studies of workers at a beryllium processing plant reported significant increases of lung cancer (Bayliss and Wagoner, 1977). There is evidence for induction of tumors by a variety of berrylium compounds via inhalation and intratracheal instillation and the induction of osteosarcomas in rabbits by intravenous or intramedullary injection in multiple studies (IRIS, 1989).

Slight increases in cancer incidences were reported in Long-Evans rats administered 5 ppm beryllium sulfate. Grossly observed tumors were reported in male rats (Schroeder and Mitchener, 1975). Significant increases in incidences of lymphoma leukemias were reported in the females relative to controls.

Reticulum cell sarcomas of the lungs were seen in the male rats when administered various doses of beryllium sulfate (Morgarcidge, et al., 1977).

Osteogenic sarcomas were induced by intraveneous injection of beryllium compounds in at least 12 different studies (U.S. EPA, 1987). Lung tumors, primarily adenomas and adenocarcinemas, have been induced via the inhalation route (Reives et al., 1967). Tumors were also induced by intratracheal instillation of metallic beryllium alloys. Adenomas, adenocarcinomas, and malignant lymphomas were seen in the lungs with lymphosarcomas and fibrosarcomas present at extrapulmonary sites (Groth, 1980).

Beryllium sulfate and beryllium chloride have been shown to be nonmutagenic in bacterial and yeast gene mutation assays (Simmon et al., 1979). Chromosomal aberrations and sister chromatid exchange were also induced by beryllium in cultured human lymphocytes and Syrain hamster embryo cells (Larramendy, 1981).

Human equivalent doses were calculated using human body weight of 70 kg, an animal weight of 0.325 kg, length of exposure. No studies indicated an increase in tumorigenic response.

Inhalation Exposure

A quantitative estimate of carcinogenic risk from inhalation exposure has been established at 8.4E+0 per (mg/kg/day)"l with an inhalation unit risk of 2.4E-3 per Vig/m1 . The estimate of risk for inhalation exposure was based on an epidemiologic study having several confounding variables. While a quantitative assessment based on several animal studies resulted in a similar estimate of risk, the quality of the available studies was poor.

Beryllium was listed as a hazardous air pollutant under Section 112 of the Clean Air Act on the basis that it can cause chronic lung disease berylliosos. Emission standards promulgated for extraction, ceramic, propellant plants, foundries, incinerators, and machine shops are 10g/24 hour or attainment of an ambient concentration near the source of .01

Toxicity to Human Health and Animals

The ambient water gualify criteria established for human health were 6. 8E-3 vq/I for water and fish consumption and 1.17E-1 ng/1 for fish consumption only. To protect aquatic organisms, acute and chronic toxicity levels are 1.3E+2 ng/1 and 5.3E+0 yg/1, respectively.

TECHNICAL PROFILE

CADMIUM

Classification

Cadmium, Cd, is unusual in relation to most substances for which an oral reference dose has been determined in that a vast quantity of both human and animal toxicity are available. This reference dose is based on the highest level of Cd, in the human renal cortex. EPA classifies cadmium as having a weight of evidence grouped in 2A being a probable carcinogen. Cadmium is also a teratogen and an experimental carcinogen.

Health Effects

The substance may attack the respiratory system, lungs, kidney, prostrate, and blood. Cadmium is inhaled or ingested. Cd studies and toxicokinetic models have been used to determine the highest level of exposure associated with the lack of a critical effect of the compound. Since the fraction of ingested cadmium that is absorbed varies with the source, it is necessary to accommodate the difference in absorption (food vs drinking water).

Oral Exposure

A high confidence level for the estimated oral reference dose of .0005 mg/kg/day (water) and .01 mg/kg/day (food) was established based on the data from many studies on the toxicity of cadmium in both humans and animals. The data permitted calculation of pharmokinetic parameters, cadmium absorption, distribution metabolism, and elimination. Chronic exposure is under review. Lung cancer risk has been observed in studies compromised by the presence of other carcinogens (arsenic, smoking) (Varner, 1983). Prostrate cancer was associated with a study relating workers to cadmium dust or fumes (Kepiing and Waterhouse, 1967), (Holden, (1980), (Sorahan and Waterhouse, 1983), but the total number of cases was small in each study. Studies of human ingestion are inadequate to assess carcinogenicity.

Animal carcinogenicity studies resulted in significant increases in lung tumors with exposure to cadmium salts (Takenaka et al., 1983). Cadmium oxides did not produce lung tumors in Fischer 344 rats but mammary tumors in females and tumors at multiple sites in the males. (Sanders and Mahaffey, 1984). Seven studies in rats and mice where cadmium salts (acetate, sulfate, chloride) wereadministered orally have shown no evidence of carcinogenic response whereas injection and distant site tumors have

been reported as a consequence of intramuscular or subcutaneous administration of cadmium metal, chloride, sulfate oxide, and sulfide compounds (U.S. EPA, 1985).

Cadmium compounds are teratogens. Mutagenicity tests in bacteria and yeasts have been inconclusive. Conflicting results have been obtained in assays of chromosomal aberrations in human lymphocytes treated in vitro.

Inhalation Exposure

Effects of arsenic and smoking were recognized in the analyses for cadmium. A slope factor for cadmium chloride inhalation data in rats equals 3.4 E-l ^g/kg/day for elemental cadmium, and the unit risk for cadmium based on this analysis is 9.2 E-2 pg/m1 (Takenaka, 1983). The carcinogenic risk from inhalation exposure establishes 6.1 E+0 ^g/kg/day as the inhalation slope factor and 1.8 E-3 ng/m for the inhalation unit risk factor. Cumulative exposure ranges from 585-2920 mg/day/m3.

Toxicity to Human Health and Animals

According to EPA's preliminary risk assessment from ambient air exposures, public health risks are significant. Thus, it intends to add cadmium to the list of hazardous air pollutants for which it intends to establish emission standards under Section H2(b)(11)(A) of the Clean Air Act.

Maximum Contaminant Level Goal (MCLG) for drinking water is .0005 mg/1 (proposed, 1985) based on the provisional DWEL of 0.018 mg/1 and drinking water contribution. A DWEL Of 0.018 mg/1 was calculated from a LOAEL of .352 mg/day for renal toxicity in humans.

The ambient water quality criteria (AWQC) for Human Health is lE-t-1 jug/1 for water and fish consumption. No levels had been established for fish only. The (AWQC) established a range for aquatic organisms from acute toxicity levels of 3.9 E+0 vig/1 to chronic toxicity levels of 1.1 E+0 ug./l for freshwater species. For marine species, an acute toxicity value of 4.3+1 jag/1 and chronic toxicity level of 9.3 E+0 jag/1 are assigned. The freshwater criteria are hardness dependent. Values given here are calculated at a hardness of 100 mg/1 calcium carbonate. Cadmium has also been found to bioaccumulate in the tissues of aquatic and marine organisms, and has the potential to concentrate in the food chain.

TECHNICAL PROFILE

CALCIUM

Pure calcium is a silvery, white metal. Its industrial use is as an alloying agent for aluminum lead and berylium. The most common form of calcium is its cationic form. It is commonly found in the environment and is essential to plant and animal life.

Classification

The weight-of-evidence for calcium is E, non-carcinogen.

Oral Exposure

There are no data for oral toxicity of calcium.

Inhalation Exposure

No information is available.

Toxicity to Human Health and Animals

Many calcium compounds are abrasive and others are caustic.

TECHNICAL PROFILE

CHROMIUM(VI)

Chromium is a naturally occuring element that is found in soil and in volcanic dusts and gasses. It is found in the environment in three major states, chromium(O), chromium(III), and chromium(VI). Chromium(III) occurs naturally in the environment, while chromium(O) and chromium(VI) are generally produced by industrial processes. Chromium(O) is the metalic form and is used in steel making and for electroplating. Other chromium compounds are made by the chemical industry for use as pigments, and in leather tanning, rubber making, wood treatment, and water treatment.

Classification

The USEPA weight-of-evidence classification for hexavalent chromium is A, human carcinogen by the inhalation route. Results of epidemiologic studies are consistent across investigators and locations. Dose-response relationships for lung tumors have been established.

Oral Exposure

No effects were seen in rats that had hexavalent chromium added to drinking water. An abrupt rise in tissue chromium concentrations was noted in rats treated with greater than 5 ppm in the diet. The authors stated that tissues can accumulate considerable quantities of chromium before pathological changes result. In the 25 ppm treatment groups, tissue concentrations of chromium were approximately 9 times higher for those treated with hexavalent chromium than for the trivalent group. Similar no-effect levels have been observed in dogs and humans.

Trivalent chromium is an essential nutrient. There is some evidence to indicate that hexavalent chromium is reduced in part to trivalent chromium in vivo.

Inhalation Exposure

A risk assessment for this substance/agent is under review by an EPA work group. Hexavalent chromium compounds have not produced lung tumors in animals by inhalation.

Toxicity to Human Health and Animals

Epidemiologic studies of chromate production facilities in the United States, Great Britain, Japan, and West Germany have

established an association between chromium (Cr) exposure and lung cancer. Most of these studies did not attempt to determine whether Cr III or Cr VI compounds were the etiologic agents.

Three studies of the chrome pigment industry, one in Norway, one in England, and the third in the Netherlands and Germany also found an association between occupational chromium exposure (predominantly to Cr VI) and lung cancer.

Hexavalent chromium compounds were carcinogenic in animal assays producing the following tumor types: intramuscular injection site tumors, intraplural implant site tumors for various chromium VI compounds, intrabronchial implantation site tumors for various Cr VI compounds, and subcutaneous injection site sarcomas.

TECHNICAL PROFILE

COBALT

Cobalt is a metalic element that occurs naturally in various valences (+l,+2,+3 rarely +4,+5) and one isotope 59CO. Cobalt appears to be essential to life with pernicious anemia developing in its absence.

Classification

Not classified for carcinogenicity by U.S. EPA.

Oral Exposure

Ingestion of soluble salts produces nausea and vomiting by local irritation (MERCK, 1989).

Inhalation Exposure

Inhalation of metalic dust may cause pulmonary symptoms. Powder may cause dermatitis (MERCK, 1989).

Toxicity to Human Health and Animals

Naturally occurring cobalt is essential to plant and animal life. There are numerous man-made cobalt compounds that are toxic in varying degrees (MERCK, 1989).

TECHNICAL PROFILE

COPPER

Copper is a red, lustrous, ductile malleable metal which is commmercially available in the form of ingots, sheets, wire, or powder. It is an excellent conductor of electricity and is widely used in the electrical industry. It is made into castings, sheets, rods, tubing and wire. Copper forms many important alloys. Copper compounds are used as insecticides, algicides, plant fungicides, pigments, in analytical reagents, in paints, and in electroplating (Sittig, 1987).

Classification

The U.S. EPA weight of evidence classification is categorized in Group D: stating that Copper and its Compounds are not classified as a human carcinogen. This classification is based on the lack of human data, inadequate animal data from assays of copper compounds and equivocal mutagenicity data (IRIS, 1990).

No human carcinogenicity data exist and animal data are inadequate. Bionetics Research Labs (1968) studied the carcinogenicity of a Copper-containing compound, copper hydroxy quinoline, in two strains of mice (B6 C3F1 and B6AKF1). No statistically significant increases in tumor incidence were observed in the treated 78-week-old animals exposed to various concentrations of copper.

In the same study, Bionetics Research labs (1968) administered a single subcutaneous injection of gelatin or 1000 mg of copper hydroxy quinoline/kg (180.6 mg/Cu/kg). After 50 days of observation, the male B63CF1 had an increased incidence of reticulum cell sarcomas compared with controls. No tumors were observed in the treated B6AKF1 mice and a low incidence of peticulum cell sarcomas was observed in the treated female mice of both strains.

Oilman (1962) administered intramuscular injections containing 20 mg of cupric oxide, cupric sulfide and cupeous sulfide into the left and right thighs of 2-3 month old Westar rats. No injection site tumors were observed in any animal after 20 months of observation, yet other tumors were observed at very low incidence in the animals receiving cupric sulfide and cupeous sulfide (IRIS, 1990)

Demeric et al. (1951) reported a dose-related mutagenic effects in E coli with 2-10 ppm copper sulfate in a reverse mutation assay. Errors in DNA synthesis from

poly(c) templates have been induced in viruses incubated with copper Chloride or copper acetate (Sirover and Loeb, 1976) . Chromosomal aberrations were induced in isolated rat hepatocytes when incubated with copper sulfate (Sina et al., 1983).

Casto et al. (1979) showed enhanced cell transformation in Syrian hamster embryo cells infected with simian adenovirus with the addition of cuprous sulfide and copper sulfate. High concentrations of copper compounds have been reported to induce mitosis in rat ascites cells and recessive lethals in Drosophilia melanogaster.

Health Effects

Copper itself has probably little or no toxicity although there are conflicting reports in lieterature (Merck, 1988). Soluble salts, notably copper sulfate, are strong irritants to the skin and mucous membranes. Copper oxide fumes can cause metal fume fever. As the sublimed oxide, copper may be responsible for one form of metal fume fever. Inhalation of copper dust has caused hemolysis of the red blood cells in animals, deposition of hemofuscin in the liver and pancreas, and injury to the lung cells. Injection of the dust has caused circhosis of the liver and pancreas and a condition closely resembling hemochromatosis or bronzed diabetes (Sax/Lewis, 1987). Considerable trial exposure to Copper compounds, however has not resulted in such disease. As regards local effects, copper chloride and sulfate have been reported a causing irritation of the skin and conjunctival which may be on an allergic basis. Cuprous oxide is irritating to the eyes and upper respiratory tract. Discoloration of the skin is often seen in persons handling copper, but this does not indicate any actual injury from copper. There is an excess of cancer cases in the copper smelting industry. In man, the ingestion of a large quantity of copper sulfate has caused vomiting, gastric pain, dizziness, exhaustion, anemia, cramps, convulsions, shock, comma and death. Symptoms attributed to damage to the nervous system and kidney have been recorded, jaundice has been observed and, in some cases, the liver has been enlarged. Deaths have been reported to have occurred following ingestion of as little as 27 grams of salt while other victims have recovered after having taken up 120 grams. Many copper containing compounds are used as fungicides.

Oral Exposure

Quantitative estimates of risks from oral exposure gives an oral Rfd of 1.3 EOO mg/kg/day (HEAST, 1990).

Inhalation Exposure

No quantitative estimates from inhalation exposure are available (IRIS, 1990).

Toxicity to Human Health and Animals

No ambient water quality criteria have been established by IRIS. To protect human health, a value of 1,000 jug/1 has been calculated. To protect freshwater and saltwater aquatic life, 5.6 ng/1 and 4.0 ug/1 are the respective values obtained in relation to hardness values.

TECHNICAL PROFILE

IRON

Iron has four naturally occurring valences (+2,+3, rarely +4,+6), and four stable isotopes. After oxygen, iron is the most commonly used element in manufacturing. Iron and its compounds have numerous uses.

Classification

Not classified for carcinogenicity by U.S. EPA.

Oral Exposure

Because of the large number of compounds, the range of toxicity by oral exposure is from non-toxic to highly toxic (MERCK, 1989).

Inhalation Exposure

Inhalation of dusts can cause irritation of mucous membranes. No other information is available.

Toxicity to Human Health and Animals

Iron is essential to most plant and animals in the naturally occurring valences (+2,+3). Some compounds may be toxic.

TECHNICAL PROFILE

LEAD

Lead (Pb) is a bluish-white, silvery-gray metal. It is used as a construction material for tank linings, piping, and other equipment handling corrosive gases and liquids used in the manufacture of sulfuric acid, petroleum refining, halogenation, sulfonation, extraction, condensation for x-ray and atomic radiation protection, manufacture of tetraethyl lead, pigments for paint, organic and inorganic lead compounds, bearing metal and alloys; storage batteries; in ceramics, plastics, and electronic devices; in building construction; in solder; and other lead alloys (Merck, 1985).

Classification

The B2 U.S. EPA classification reflects a weight of evidence judgement of the likelihood that the agent is a human carcinogen based on sufficient animal evidence. Ten rat bioassays and one mouse assay have shown statistically significant increases in renal tumors with dietary and subcutaneous exposure to several soluble lead salts. Animal assays provide reproducible results in several in multiple rat strains with some evidence of multiple tumor sites. Short-term studies show that lead affects gene expression.

Human evidence is inadequate. Four epidemiologic studies in occupational cohorts exposed to lead and lead compounds were conducted. Two studies did not find any association between exposure to lead and cancer mortality (Dingwall-Fordyce and Lane, 1963, Nelson et al. 1982). Selevan et al. (1985) in their retrospective cohort mortality study of primary lead smelter workers found a slight decrease in the total cancer mortality. Excesses for respiratory and kidney cancer were observed. Cooper and Gaffey (1975) and Cooper (1985 update) in their cohort mortality study of battery plant and lead smelter workers found statistically significant excesses for total cancer mortality, stomach cancer, and lung cancer in battery plant workers. Cooper and Gaffey (1975) monitored individual subjects primarily on the basis of obvious signs of lead exposure while others who showed no symptoms of lead poisoning were not monitored.

All of the available studies lacked dose-response relationships and quantitative exposure information. All studies had exposure to other metals, such as arsenic, cadmium, and zinc for which no adjustment was done. Human evidence is considered to be inadequate to refute or demonstrate potential carcinogenicity for humans from lead exposure (IRIS, 1989).

Animal carcinogenicity data are sufficient. The carcinogenic potential of lead salts, primarily phosphates, and acetates administered by the oral route, diet, or by injection has been demonstrated in rats and mice by more than 10 investigations. The most characteristic cancer response is bilateral renal carcinoma. Rats given lead acetate or subacetate developed gilimas, and lung adenomas at high dosages displayed a carcinogenic response. Metallic lead, lead oxide, and lead tetralkyls have not been tested adequately.

One hundred control rats of each sex received the basal laboratory diet. In a second two-year study, 20 rats were given diets containing various doses of lead acetate. No renal tumors were reported in the control groups or in treated animals of either sex receiving 10 to 100 ppm. Male rats fed 50-2,000 ppm lead acetate had an increased renal tumor incidence. Renal tumors were observed in doses in the 2,000 ppm.

No kidney tumors were detected among the 10 control rats that were given lead acetate in their drinking water for 76 weeks (Koller et al., 1986). Six of 25 male mice of 0.1% basic lead acetate group had renal tumors (adenomas and carcinomas combined). Kasprzak et al. (1985) investigated the interaction of dietary calcium on lead carcinogenicity and fed a diet with 1% lead subacetate to male Sprague-Dawley rats for 79 weeks of the rats surviving beyond 58 weeks in this treatment group. Forty-five percent had renal tumors. Four rats had adenocarcinomas and the remaining nine had adenomas. Bilateral tumors were noted.

Lead acetate induces cell transformation in Syrian hamster embryo cells as well as enhances the incidences of semian adenovirus induction (D. Paola et al., 1978). Lead oxide showed similar enhanced adenovirus induction (Casto et al., 1979). Lead compounds are capable of inducing chromosomal aberrations in vivo and in tissue cultures. Grandyron et al. (1983) showed a relationship between SCE and lead exposure in workers. Lead has been shown, in a number of DNA structures and function assays, to affect the molecular processes associated with the regulation of gene expression (U.S. EPA, 1986).

Health Effects

Lead poisoning is one of the commonest of occupational diseases. The presence of lead-bearing materials or lead compounds in an industrial plant does not necessarily result in exposure on the part of the worker. The lead must be in such form, and so distributed, as to gain entrance into the body or tissues of the worker in

measurable quantity, otherwise no exposure can be said to exist. Some are carcinogens of the lungs and kidneys. Others are experimental neoplastigens and tumorigens. The modes of entry into the body are by inhalation of dusts, fumes, mists or vapors; by ingestion of lead compounds trapped in the upper respiratory tract or introduced into the mouth on food, tobacco, fingers, or other objects; and through the skin. This route is of special importance in the case of organic compounds of lead, such as lead tetraethyl. In the case of inorganic forms of lead, this route is of no practical importance.

When lead is ingested, much of it passes through the body unabsorbed, and is eliminated in the feces. The greater portion of the lead that is absorbed is caught by the liver and excreted in part in the bile. For this reason, larger amounts of lead are necessary to cause poisoning if absorption is by this route, and a longer period of exposure is usually necessary to produce symptoms. Upon inhalation, absorption takes place easily from the respiratory tract and symptoms tend to develop more quickly. From the point of view of industrial poisoning, inhalation of lead is much more important than ingestion, Lead is a cumulative poison. Increasing amounts build up in the body and eventually a point is reached where symptoms and disability occur. Lead produces a britleness of the red blood cells so that they hemolyze with slight trauma; the hemoglobin is not affected. Due to their increased fragility, the red blood cells are destroyed more rapidly in the body than normally, producing an anemia that is rarely severe. The loss of circulating red cells stimulates the production of new young cells, which on entering the blood stream, are acted upon by the circulating lead, with resultant coagulation of their basophilic material. Lead produces a damaging effect on the organs or tissues with which it comes into contact. Systemic effects include decreased physical fitness, fatigue, sleep, headache, aching bones and muscles, digestive symptoms, abdominal pains, and decreased appetite. Later findings include anemia, palloc, and "lead line" of the gums. Lead colic produces an intense periodic abdominal cramping associated with severe constipation, nausea, and vomiting. Alcohol ingestion and physical exertion may precipitate these symptoms. The peripheral nerve affected most frequently is the radial nerve. When the central nervous system is affected, it is usually due to the ingestion or inhalation of large amounts of lead. This results in severe headache, convulsions, coma, delerium, and possible death. The kidneys can also be damaged after long periods of exposure to lead with loss of kidney function and progressive azotemia. In case of lead poisoning, the

amount of lead found in the blood is frequently in excess of 0.07 mg/1 of blood.

Oral Exposure

Quantifying lead's cancer risk involves many uncertainties, some of which may be unique to lead. Age, health, nutritional state, body burden and exposure duration influence the absorption, release and excretion of lead. Lead pharmacokinetics indicates that an estimate derived by standard procedures would not truly describe the potential risk. Thus, the Caricinogen Assessment Group recommends that a numerical estimate not be used.

Inhalation Exposure

No quantitative estimate of carcinogenic risk from inhalation exposure is available.

Toxicity to Human Health and Animals

The U.S. EPA has set a primary National Ambient Air Quality Standard (NAAQS) for lead of 1.5 mg/m1. The secondary NAAQS is identical to the primary standard. The EPA is currently reviewing these standards to determine if changes are warranted.

A maximum containment level goal (MCLG) for drinking water of 0.02 mg/1 was proposed in 1985 (IRIS, 1989). Neurological effects of lead in infants and adverse effects associated with blood lead levels of 15 ug/1 are the basis for this MCLG. A level of 0.02 mg/1 for lead was derived.

An ambient water qualty criterion for human health has been calculated at 5.0E+1 pg/l for water and fish consumption. This criterion was set at the existing drinking water standard in 1980. The acute toxicity levels for freshwater and marine organisms are 8.2E+1 ng/1 and 1.4E+2 ug/1, respectively. The toxicity of this compound is hardness-dependent. Chronic toxicity values are 3.2E+0 mg/1 and 5.6E+0 mg/1 for freshwater and marine organisms, respectively.

TECHNICAL PROFILE

MAGNESIUM

Magnesium is considered to be the lightest structural metal. It is found in nature in the +2 valence. It is essential to life, especially green plants.

Classification

Magnesium is not classified by U.S. EPA for carcinogenicity.

Oral Exposure

None available.

Inhalation Exposure

None available.

Toxicity to Human Health and Animals

Particles embedded in skin can produce gaseous blebs with a protracted course. Inhaling the dust is irritating, and fumes can cause metal fume fever.

TECHNICAL PROFILE

MANGANESE

Manganese is a steel gray, lustrous, hard, brittle metal. It is primarily used in the manufacture of steel, for rock crushers, railway points and crossings, and as a constituent of several alloys.

Classification

The U.S. EPA weight of evidence classification is categorized as being in Group D: not classified as a human carcinogin based on limited evidence to evaluate carcinogenicity in humans and animals. No human carcinogenicity data exist. Animal carcinogenic data are inadequate. D. Paolo's (1964) study evaluated the effects of manganese chloride subcutaneously or intraperitoneally injected in mice. 67% of the mice expososed subcutaneously and intraperitoneally, developed lymphosarcomas compared with controls injected with water. In addition, tumors appeared earlier in the exposed groups than in the control groups. A thorough evaluation of the results of this study was not possible because the results were published in abstract form.

Stoner et al. (1976) tested manganeous sulfate in a mouse lung adenoma screening bioassay (IRIS, 1989). Groups of strain A/Strong mice (10/sex), 6-8 weeks old, were exposed by intraperitoneal injection to 0,6,15 or 30 mg/kg manganous sulfate 3 times per week for 7 weeks.

The animals were observed for an additional 22 weeks after the dosing period. An apparent increase in the average number of pulmonary adenomas per mouse both at med and high doses as compared with the vehicle controls, but the increase was significant only at high doses. The percentage of mice with tumors was elevated slightly but not significantly.

Shemkin and Stoner's mouse lung adenoma bioassay noted that certain specific criteria should be met in order for a response to be considered positive (IRIS, 1990). Among these criteria are an increase in the mean number of tumors per mouse and an evident dose-response relationship. While the results of this study are suggestive of carcinogenicity, the data cannot be considered conclusive since the mean number of tumors per mouse was significantly increased at only one dose, and the evidence for a dose-response relationship are marginal,

Furst (1978) exposed groups of F344 rats (25/sex) intramuscularily or by gavage to manganese powder, manganese dioxide and manganese (II) acetylacetonate (MAA). There was an increased incidence of fibrosarcomas at the injectin site in male (40%) and female (24%) rats exposed intramuscularly to MAA compared with vehicle controls. EPA (1984) determined that these increases were statistically significant. No difference in tumor incidence was found between rats and mice exposed to manganese powder and manganese oxide and Controls. The U.S. EPA (1984) noted that the study results regarding MAA, an organic manganese compound, cannot necessarily be extrapolated to pure manganese or other inorganic manganese compounds.

Witschi et al. (1981) exposed female A/J mice intraperitoneally to 80 mg/kg methyl cyclopentddienyl manganese tricarbonage (MMT) and found that although cell proliferation was produced in the lungs, lung tumor incidence did not increase (IRIS, 1990).

Health Effects

Manganese compounds can cause central nervous system and pulmonary system damage by inhalation of fumes and dust. It is an experimental tumorigin. Chronic manganese poisoning is a clearly characterized disease which results from the inhalation of fumes or dusts of manganese. Exposure to heavy concentrations of dusts or fumes for as little as three months may produce the condition, but usually cases develop after the 1-3 years of exposure. The central nervous system is the chief site of damage. If cases are removed from exposure shortly after the appearance of symptoms, some improvement in the patients condition frequently occurs, though there may be some residual disturbances in gart and speech. When well established, however, the disease results in permanent disability. Exposure to dusts and fumes can possibly increase the incidence of upper respiratory infections and pneumonia. Chronic manganese poisoning begins usually with complaints of language and sleepiness. This is followed by weakness in the legs and the development of a stolid-mask-like face, and the patient speaks with a slow monotonous voice. The muscular twitchings appear, varying from a fine tremor of the hands to coarse, rhythmical movements of the arms, legs and trunk. Nocturnal cramps of the leg appear about the same time. There is a slight increase in the tendon reflexes, ankle and patillar clonus, and a typical Parkinsonian slopping gait. The handwriting may be quite minute. The systems may simulate progressive bulbar paralysis, postincephalitec

Parkinsonism, multiple sclerosis, amyotropic lateral sclerosis and progressive lenticulae degeneration (Welson's Disease).

Oral Exposure

A quantitative estimate from oral exposure is available with an oral reference dose of 2E-1, (USEPA, 1986).

Inhalation Exposure

No quantitative estimate of Carcinogenic risk from inhalation exposure is available. No inhalation references are available (IRIS, 1990).

Toxicity to Human Health and Animals

No ambient water quality criteria have been established for toxicity to human health and aquatic organisms (IRIS, 1990). Federal standards for manganese dusts and compound is 5 mg/m3 as a ceiling value. The U.S. EPA has suggested 50 ng/1 for domestic water supplies and 100 ]j/l for protection of consumers of marine mollusks.

TECHNICAL PROFILE

MERCURY

Mercury, Hg, is a silver-white, heavy, mobile, liquid metal utilized in gold, silver, and bronze tin-plating; tanning and dying; feltmaking; taxidermy; textile manufactures; photographing; extracting gold and silver from ores; paints and pigments; the preparation of drugs and disinfectants in the pharmaceutical industry; and as a chemical reagent.

Classification

The U.S. EPA weight of evidence classification for human carcinogenicity is categorized in Group D: not being a human carcinogen. No human carcinogenicity data are available to evaluate the evidence for carcinogenicity. Animal carcinogenicity studies are inadequate. A study was conducted to observe the effects of mercury when 39 rats were injected over two weeks and for their lifetime. (Druckrey et al., 1957). Sarcomas were seen only in those tissues that had been in direct contact with the metal. Mitsumori et al. (1981) fed groups of 60 male and 60 female SPF ICR mice 0, 15, or 30 ppm methyl mercury chloride in the diet for up to 78 weeks. The majority of the 30 ppm groups died from neurotoxicity by the 26th week. Renal tumors were revealed on kidney tissue from animals surviving after 53 weeks (IRIS, 1989). One adenoma was detected among 37 controls surviving to week 53 or beyond, and no tumors were seem in either control or exposed females. The possible presence of tumors at other sites was not reported.

Health Effects

Mercury can be inhaled, ingested, or affect the eyes and skin. It is a primary irritant of skin and mucous membranes. It may be a skin sensitizer. Either acute or chronic exposure may produce permanent changes to affected organs and organ systems. Soluble mercury salts have violent corrosive effects on skin and mucous membranes, cause severe nausea, vomiting, abdominal pain, and bloody diarrhea; kidney damage, and death usually within 10 days. Chronic effects produce four classical signs: gingivitis, sealorrhea, increased irritability, and muscular tremors. Rarely are all four seen togther in an individual case. Symptoms may include inflammation of the mouth or gums, excessive salivation, brasing of teeth, kidney damage, muscle tremors, personality changes, depression, irritability, and nervousness. Burning sensation is delayed several hours and thus gives no warning.

Oral Exposure

Presently, no quantitative estimates of carcinogenic risks from oral exposure are available. Methyl mercury hydroxide administered in the diet to Drosophila melanogaster at 5 mg/1 induced chromosomal nondisjunction. Methyl and phenyl mercury produced small increases in the rate of point mutations (Ramel, 1972).

Inhalation Exposure

No quantitative estimates of carcinogenic risks from inhalation exposure are presently available. An inhalation reference dose is pending a review of the risk assessment.

Toxicity to Human Health and Animals

Ambient water quality criteria have not been calculated for human health and aquatic organisms (IRIS, 1989). The federal standard from mercury is 0.1 mg/m1 as a ceiling value (Settig, 1985). The National Institute for Occupational Safety and Health's (NIOSH) recommended standard is 0.05 mg/m1 as a time weighted average (TWA). To protect freshwater aquatic life, .00057 jig/l as a 24-hour average, never to exceed . 0017/ng/l, was calculated. To protect saltwater aquatic life, a level of 0.025 ng/1 as a 24-hour average, never to exceed 3.7 ug/1, was calculated. Likewise, 0.144 vig/1 was calculated as a value to protect human health (Sittig, 1985) (U.S. EPA - 1980).

TECHNICAL PROFILE

NICKEL

Nickel, Ni, is a lustrous, hard ferromagnetic material. It is used for nickel plating, for various alloys, for coins, storage batteries, magnets, lightening rod tips, machinery parts; catalyst for the hydrogenation of oils and other organic substances. Probably the most use of nickel is in the manufacture of Manel metal, stainless steels, nickel-chrome resistence wires, and in alloys for electronic and space applications (Merck, 1987).

Classification

The U.S. EPA weight of evidence classification is categorized in Group A: stating nickel to be a human carcinogen. This classification is based on human data in which exposure to nickel refinery dust caused lung and nasal tumors in sulfide nickel matte refinery workers in several epidemiologic studies in different countries, and on animal data in which carcinomas were produced in rats by inhalation and injection.

Sufficient human carcinogenicity data exist. Nickel refinery dust from pyromethallurgical sulfide nickel matte refineries is considered a human carcinogen when inhaled. Evidence of carcinogenicity includes a consistency of findings across different countries in several epidemiologic studies (Clydach, Wales; Copper Cliff, Ontario; Port Colborne, Ontario; Kristiansand Norway and Huntington, West Virginia). Specific tumor sites (lung and nose), high relative risks, particularly for nasal cancer and dose response relationships by length of exposure have been examined. Excess risks are greatest in the dustier areas of the respective refineries. Roberts et al. (1983) reported high risk of lung (SMR=298) and nasal (SMR=9412) cancer among men "ever exposed" to calcining, leaching; and sintering the dustier areas of the refinery. Similar exposures and high risks of lung and nasal cancer were observed in the calcining sheds. In the study of refinery and nonrefinery workers at a nickel refinery in West Virginia, nasal cancer was exclusive to the refinery workers, with an SMR of 2443 (Enterline and Marsh, 1982). No large excess of lung cancer was observed in either refinery or nonrefinery employees. A dose-response relationship is consistent with findings at nickel refineries in Clydach, Wales. While the dust levels and lung cancer relative risks were much higher, all dose-response relationships appeared linear and the tumor type and sites are the same, indicating that the functional relationship spans a broad range of nickel exposure.

Animal studies indicate some nickel refinery dusts are potentially carcinogenic.

Nickel refinery flue dust was found to be a strong inducer of injection-site sarcomas in Hooded (52/66) and Wistar (8/20) rats after injection of 20 or 30 mg in one or both thighs and in mice (23/40) after injection of 10 mg/thigh. Fisher et al. (1971), as reviewed by Rigaut (1983), tested nickel refinery dust by inhalation. The refinery dust was one of six types of dust exposures administered to 348 rats at 5 to 15 mg/m3. The combined tumor incidence for refinery dust, synthetic dust, nickel subsulfide, and iron sulfide was 11 pulmonary tumors in the 348 rats. One of 60 surviving rats developed lung cancer when Wistar rats were exposed to a combination of nickel and iron dust (Kim et al., 1976).

Nickel dust from roasting was tested for carcinogenicity in rats by inhalation (Belobragina and Saknyn, 1964, as reviewed by Rigaut, 1983). No tumors were found after exposure to 80-100 mg/mj, 5 hours/day for twelve months. Ambrose et al. (1976) administered nickel sulfate hexahydrate in the diet of Wistar-derived rats and beagle dogs for 2 years at nickel concentrations of 100 to 2,500 ppm. A lack of carcinogenic response was observed in both studies.

Health Effects

Nickel and most of its salts are generally considered not to cause acute systemic poisoning. However, ingest ion of large doses of nickel compounds have been shown to cause intestinal disorders, convulsions, and asphyxia. Many nickel compounds are experimental carcinogens and some are human carcinogens by inhalation. All airborne nickel contaminating dusts are regarded as carcinogenic by inhalation. The most common effect resulting from exposure to nickel compounds is the development of the "nickel itch," This form of dermatitis occurs chiefly in persons doing nickel-plating. There is marked variation in individual susceptibility to the dermatitis. It occurs more freqently under conditions of high temperature and humidity, when the skin is moist and chiefly affects the hands and arms. Nickel carbonyl is highly irritating to the lungs and also can produce asphyxia by decomposing with the formation of carbon monoxide. These compounds are common air contaminants (Sax/Lewis, 1987).

Oral Exposure

Quantitative estimates of carcinogenic risks are not available.

Inhalation Exposure

An inhalation slope factor of 8.4E-1 mg/kg/day"' and an inhalation unit risk were calculated to be 2.4E-4 ng/m1. Air concentrations at specified risk levels are 4E-1 pg/m3, 4E-2 ng/m1, and 4E-3 ng/m3 for risk levels of 1 in 10,000, l in 100,000 and 1 in 1,000,000, respectively (IRIS, 1990).

Toxicity to Human Health and Animals

To protect human health, a value of -13.4 pg/1 has been assigned. No ambient water quality criteria have been established for human health and aquatic organisms (IRIS, 1990). The Federal standard for nickel metal and its soluble compounds is 1 mg/m1. To protect freshwater aquatic life e [0.76 in hardness) +4.02 has been calculated. To protect saltwater aquatic life, -7.1 pg/1 is evaluated for a 24-hour average, never to exceed 140 ng/1 (Sittig, 1985).

TECHNICAL PROFILE

POTASSIUM

Potassium is found widly in nature in the form of its compound. It is essential to life as a basic component on numerous biological compounds such as proteins and lipids.

Classification

Potassium is not classified by U.S. EPA for carcinogenicity.

Oral Exposure

There is no general toxicity although some compounds may have effects. No specific information is available.

Inhalation Exposure

Inhalation of some inorganic salts can cause toxic effects, although no specific information is available.

Toxicity to Human Health and Animals

No additional information is available.

TECHNICAL PROFILE

SELENIUM

Selenium is naturally occurring in rock and soils but is unevenly distributed. Selenium is found as any one of a number of compounds. Selenium is an essential element to life, however, high doses are harmful.

Classification

There are no data to support EPA classification of carcinogenicity for selenium.

Oral Exposure

The normal intake of selenium is 150 mg/day. Higher amounts can be harmful causing brittle hair, deformed nails, and loss of feeling and control in arms and legs.

Inhalation Exposure

Hydrogen selenide poses a health hazard in some industrial settings. No other data concerning inhalation effects are available.

Toxicity to Human Health and Animals

Selenium is found in coal at varying concentrations. Selenium is not lost when coal is burned, and thus concentrates in the ash. Soluble selenium compounds can escape from ash and enter the ecosystem. Effects on fish and wildlife include feto toxicity and altered embryonic development (ASTDR, 1989).

TECHNICAL PROFILE

SILVER

Silver, Ag, is a white metal that is more malleable and dichite than any other metal except gold. It is an excellent conductor of heat and electricity. It is used for coinage, most frequently alloyed with copper or gold; for manufacturing tableware, mirrors, jewelry, ornaments, for electroplating; for use in the manufacture of medicinal chemicals, in processing foods and beverages, in handling organic acids; as a catalyst in hydrogeneration and oxidation processes and as an ingredient of dental alloys (Merck, 1987).

Classification

The evidence for classification by the U.S. EPA as to human carcinogenicity is classified as Group D: not classified as a human carcinogen. The basis of this classification is due to the lack of evidence of cancer in humans despite frequent therapeutic use of the compound over the years. Animal carcinogenicity data are inadequate. In animals, local sarcomas have been induced after implantation of foils and discs of silver. However, the interpretation of these findings has been questioned due to the phenomenon of solid-state carcinogenesis in which even insoluble solids, such as plastic, have been shown to result in local fibro sarcomas (IRIS, 1990).

Local sarcomas have been induced after subcutaneous implantation of foils and discs of silver and other noble metals. Furst, (1981), cited studies that even insoluble solids, such as smooth ivory and plastic, result in local fibrosarcomas and that tin when crumbled will not. Implants were concluded invalid as indicators of carcinogenicity because of a phenomenon called solid-state carcinogenesis may complicate the interpretation of the cause of these tumors. It is difficult to interpret these implantation site tumors in laboratory animals in terms of exposure to humans via ingestion.

Schmahl and Steinhoff (1960) reported, in a study of silver and of gold, that colloidal silver injected both I.V. and S.C. into rats resulted in tumors in 8 of 26 rats which survived longer than 14 months. In 6 of the 8, the tumor was at the site of the S.C. injection. In about 700 untreated rats, the rate of spontaneous tumor formation of any site was 1 to 3%.

Fuest and Schlauder (1977) evaluated silver and gold for carcinogenicity in a study designed to avoid solid-state carcinogenesis. Metal powder was suspended in trioctanoin and injected monthly into 50 male and female Fischer 344 rats per groups. The dose was 5 mg each for 5 treatments and 10 mg each for 5 more treatments for a total dose of 75 mg silver. The treatment regimen included a vehicle control, and a cadmium as a positive control. Injection site sarcomas were found only in vehicle control (1/50), gold (1/50), and cadmium (30/50); no tumors (0/50) appeared at the site of injection in the silver-treated animals. A complete necropsy was performed on all animals. They concluded that finely divided silver powder injected does not induce cancer.

Further support for the lack of silver's ability to induce or promote cancer stems from the finding that there are no reports of cancer associated with silver. In a recent Poceedings of a Workshop/Conference on the role of metals in Carcinogenesis (1981) containing 24 articles on animal bioassays, epidemiology, biochemistry, mutagenicity, and enhancement and inhibition of carcinogenesis, silver was not included as a metal of carcinogenic concern.

No evidence of the mutagenicity of Silver was shown in two available studies. Demeric et al. (1951) studied silver nitrate for the possible induction of back-mutations from striptomycin dependence to nondependence in Escherecha coli. Silver nitrate was considered nonmutagenic. Nishioka (1975) screened silver chloride with other chemicals for mutagenic effects using a method called the rec-assay. Silver chloride was considered nonmutagenic in this assay (IRIS, 1990).

Oral Exposure

The quantitative estimate of risk from oral exposure is 3E-3 mg/kg/day (HEAST, 1990).

Inhalation Exposure

No quantitative estimate of carcinogenic risk from inhalation exposure is available.

Toxicity to Human Health and Animals

A maximum contaminant level (MCL) for drinking water is 0.05 mg/1 (1980). An ambient water quality criteria (AWQC) has been calculated for human health. 50 ng/1 is calculated as the toxicity level for water and fish consumption. The value is the same as the drinking water standard and approximates a safe level assuming

consumption of contaminated organisms and water. For aquatic organisms, an acute toxicity level varies with hardness for freshwater organisms. For freshwater aquatic life, the concentration in (ng/1) of total receivable silver should not exceed the numerical value. A chronic toxicity level of 1.2 E-l|ag/l has been calculated for the freshwater chronic criterion.

TECHNICAL PROFILE

SODIUM

Sodium is a silvery white metal that, in the form of its compounds, comprises three percent of the earth's crust. Its major source is sodium chloride, the major inorganic component of sea water.

Classification

Sodium is not classified for carcinogenicity.

Oral Exposure

No specific data exist.

Inhalation Exposure

No specific data exist.

Toxicity to Human Health and Animals

Sodium is essential to life in its ionic form. Some compounds are toxic and are dealt with specifically rather than generally. Sodium metal is highly reactive and is not likely to be found in the environment.

TECHNICAL PROFILE

THALLIUM

Thallium is a heavy metal. It has limited industrial use. Thallic compounds have a history of use as rat poison.

Classification

Thallium is not classified by U.S. EPA for carcinogenicity.

Oral Exposure

No information is available.

Inhalation Exposure

No information is available.

Toxicity to Human Health and Animals

Symptoms of acute toxicity include nausea, vomiting, diarrhea, tingling, pain in extremities, weakness, coma, convulsions, and death. Symptoms of chronic toxicity include weakness and pain in extremities and hair loss.

TECHNICAL PROFILE

VANADIUM

Vanadium is a heavy metal used in the manufacture of rust resistant steel. It occurs naturally in mineral ores.

Classification

Not classified.

Oral Exposure

None available.

Inhalation Exposure

None available.

Toxicity to Human Health and Animals

Vanadium compounds are toxic to humans and animals, and is considered to be an industrial hazard. Dust from vanadium and its compounds is irritating to the respiratory tract, but the effects are not long lasting or cumulative.

TECHNICAL PROFILE

ZINC

Zinc is a metal with many uses in industry. It can be found in pure form or mixed with other metals to form alloys such as brass, or chemical salts such as zinc chloride. Zinc compounds are found naturally in air, soil and water, and are present in most foods. It is an essential food element needed by the body in low doses. Zinc can be harmful to the body if too much is taken in.

Classification

USEPA weight-of-evidence classification for zinc is D, not classifiable as to human carcinogenicity on the basis of inadequate evidence in humans and animals.

Oral Exposure

A risk assessment for this substance/agent is under review by an EPA work group.

Inhalation Exposure

Not available at this time.

Toxicity to Human Health and Animals

There are no reports on the possible carcinogenicity of zinc and compounds per se in humans. Case studies have been used to evaluate the effects of zinc administered for therapeutic reasons. There are reports which compare zinc levels in normal and cancerous tissue. Studies of occupational exposure to zinc compounds have also been conducted, but have limited value because they do not correlate exposure with cancer risk.

TECHNICAL PROFILE

CYANIDE (NOS)

Classification

Cyanide (NOS) is used primarily in the extraction of ores, electroplating, metal treatment, and various manufacturing processes. Cyanide is commonly found in certain rat and pest poisons, silver and metal polishes, photographic solutions, and fumigating products. The weight of evidence for classification as to human carcinoginicity is categorized in Group D and is not classified as a human carcinogen. Pertinent data regarding human and animal carcinogenicity have not been located. In viro studies of genotoxicity have been negative except for a marginally mutagenic response for HCN in Salmonella typhimurium strain TA-1OO (Kushi et al., 1983). This response was decreased in the presence of rat hepatic homogenates.

Health Effects

Cyanides are extremely poisonous. Death can occur within seconds of inhalation or ingestion. Cyanide is readily absorbed from all routes, including the skin, mumem, and by inhalation, although alkali salts are toxic when ingested. Death may occur with ingestion of even small amounts of cyanide compounds and can occur within minutes or hours depending on route of exposure. Inhalation of toxic fumes represents a potentially rapidly fatal type of exposure. Lifetime health advisories are not derived for compounds which are potentially carcinogenic for humans because of the difference in assumptions concerning toxic threshold for carcinogenic and noncarcinogenic effects. A one-day health advisory for a child is not available. A modified drinking water equivalent level (DWEL) of .22 mg/1 may be used. A blood cyanide level of greater than 0.2 ng/ml is considered toxic (Sittig, 1983). Lethal cases have usually had levels above 1 ng/ml. Appropriate data for calculating long-term health advisories are not available. The recommended DWEL of 0.77 mg/1 may be used for the 70-kg adult. The DWEL has been established to be 7.7 E-l mg/L. A two liter per day water consumption is assumed for a 70-kg adult. A lifetime health advisory is calculated to be 1.54 E-l mg/1 assuming a 20% drinking water exposure (Howard and Hanzal, 1955) .

Oral Exposure

Howard and Hanzal studied chronic toxic effects to rats of food treated with hydrogen cyanide. There were no treatment-related effects on growth rate, no gross signs

of toxicity, and no pathologic lesions. Studies by Philbrick et al. (1979) showed decreased weight gain and thyroxin levels and myelin degeneration in rats at 30 mg/kg/day CN. The oral reference dose for chronic exposure is 2E-2 mg/kg/day. Other chronic studies gave higher effect levels or used the subcutaneous route (Crampton et al., 1979). Human data do not provide adequate information from which to derive a reference dose because effective dose levels of ingested CN are not documented. Therefore, the study of Howard and Hanzel (1955) provides the highest NOAEL, 10.8 mg/kg/day for CN, and is chosen for the derivation of a reference dose for CN of 1.5 mg/day or 0.02 mg/kg/day. Decreased protein efficiency was produced by dietary cyanide treatment of rats during gestation, lactation, and postweaning growth in studies conducted by Tewe and Manu (1981). Dose levels of cyanide producing that effect is slightly lower than accepted NOAEL of 10.8 mg/kg/day (U.S. EPA, 1985). Effects observed at 9.45 mg/kg/day were proliferation of glomerular cells of the kidneys, and reduced activity of the thyroid glands in the gilts. A Japanese study (Amo, 1973) indicated that 0.05 mg/kg/day of cyanide obtained from drinking water decreased the fertility and survival rate and produced 100% mortality in F2 generation in mice. These data are not consistent with available data. A medium level of oral reference dose confidence to these studies has been assigned because inadequate records of food consumption and body weight were maintained and small but sufficient studies support the chosen study. Additional chronic reproduction studies are needed.

Inhalation Exposure

No chronic inhalation reference dose is available. No quantitative estimates of carcinogenic risk from inhalation exposure are available.

Toxicity to Human Health and Animals

Ambient water quality criteria (AWQC) have been established for human health and aquatic organisms. A level of 2E+2 ng/1 is value established for water and fish consumption. This level is the same as the drinking water standard and approximates a safe level assuming consumption of contaminated organisms and water.

The acute levels for freshwater and marine organisms are 2.2 E+l ng/1 and 1 E+0 vig/1, respectively. Chronic levels are 5.2 E+0 ng/1 for freshwater organisms. Marine organisms do not have associated chronic levels. AWQC for the protection of aquatic life are derived from a minimum

data base of acute and chronic tests on a variety of aquatic organisms. The acute criteria maximum concentration is a one-hour average, and the chronic criteria continuous concentration is a four-day average that is not to be exceeded more than once every three years.

REFERENCES

Bishop, W.E., Maki, A.W. 1980. A critical comparison of two bioconcentration test methods. Aquatic Toxicology, ASTM STP 707, J.G. Eaton, P.R. Parrish, A.C. Hendricks, eds. American Society for Testing and Materials. Philadelphia, Pennsylvania.

Buckingham, J. 1984. Dictionary of Organic Compounds. Chapman and Hall. New York, New York.

Callahan, M.A., M.W. Slimak, N.W. Gabel, I.P. May, C.F. Fowler, J.R. Freed, P. Jennings, R.L. Durfee, F.C. Whitmore, B. Maestri, W.R. Mabey, B.R. Holt, C. Gould. 1979. Water Related Environmental Fate of 129 Priority Pollutants. Volume I: Introduction and Technical Background, Metals and Inorganics, Pesticides, and PCBs. U.S. EPA. Washington, D.C. EPA-440/4-79-029a.

. 1979 Water Related Environmental Fate of 129 Priority Pollutants. Volume II: Halogenated Aliphatic Hydrocarbons, Halogenated Ethers, Monocyclic Aromatics, Phthalate Esters, PAHs, Nitrosamines, and Miscellaneous Compounds. U.S. EPA. Washington, D.C. EPA-440/4-79-029b.

Hilsenhoff, W.L. 1988. Rapid field assessment of organic pollution with family level biotic index. J. Am. Ornithol. Soc. 7(1) 65-68.

Kenaga, E.E., C.A.I. Goring. 1980. Relationship between water solubility, soil sorption, octanol-water partitioning, and concentration of chemicals in biota. Aquatic Toxicology. ASTM STP 707. J.G. Eaton, P.R. Parrish, A.C. Hendricks, eds. American Society for Testing and Materials. Philadelphia, Pennsylvania.

Mabey, W.R., J.H. Smith, R.T. Podoll, H.L. Johnson, T. Mill, W. Chou, J. Gates, I.W. Partridge, D. Vandenberg. 1982. Aguatic Fate and Process Data for Organic Priority Pollutants. U.S. EPA. 440/4-81-014. Washington, D.C.

Massachusetts Department of Environmental Quality Engineering, Office of Research and Standards. 1989. Guidance for disposal site risk characterization and related phase II activities - in support of the Massachusetts contingency plan. Office of the Massachusetts Secretary of State. Boston, Massachusetts.

Sax, I.N., R.J. Lewis, Sr. 1987. Hazardous chemicals desk reference. Van Nostrand Reinhold Company, Inc. New York.

Sax, I.N. 1984. Dangerous Properties of Industrial Materials, 6th Edition. Van Nostrand Reinhold Company, Inc. New York.

Sittig, M. 1985. Handbook of Toxic and Hazardous Chemicals and Carcinogens, Second Edition. Noyes Publications. Park Ridge, New Jersey.

U.S. Environmental Protection Agency. (Continuously Updated). Integrated Risk Information System (IRIS).

. 1985. Chemical emergency prepardness program: chemical profiles. U.S. EPA, Washington, D.C.

. 1986. Superfund public health evaluation manual. U.S. EPA Office of Emergency and Remedial Response, Office of Solid Waste and Emergency Response. Washington, D.C. EPA 540/1-86/060.

. 1988. Superfund exposure assessment manual. U.S. Environmental Protection Agency, Office of Remedial Response, Washington, D.C. EPA/540/1-88/001.

. 1989. Risk assessment guidance for Superfund. Human Health Evaluation Manual, Part A, Interim Final. U.S. EPA. Office of Emergency and Remedial Response. OSWER Directive 9285.7-Ola. Washington, D.C.

Warren-Hicks, W., B.R. Parkhurst, S.S. Baker, Jr. 1989. Ecological assessment of hazardous waste sites: a field and laboratory reference. U.S. EPA, Environmental Research Laboratory. Corvallis, OR. EPA/600/3-89/013.

Weast, R.C., M.J. Astle, CRC Handbook of Data on Organic Compounds. CRC Press, Inc. Boca Raton, Florida.

Windholz, M. 1983. The Merck Index, 10th Edition. Merck and Co. Inc. Rahway, New Jersey.