international regulatory and research activities

Chapter 9

International Regulatoryand Research Activities

‘‘The need for generally accepted scientific principles and requirements in all areas of toxicology particularlyapplies to the newly developed field of neurotoxicology. Methods continue to be developed in isolation, andthe comparability of results is often in doubt. Furthermore, until scientific principles have been agreed on,internationally accepted strategies to test the effects of chemicals on the many functions of the mammaliannervous system will not be developed. ”

Principles and Methods for the Assessment ofNeurotoxicity Associated With Exposure to Chemicals

World Health Organization, 1986

“The NACA supports additional neurotoxicological and behavioral effects testing as a legitimate componentof the requirements for re-registration and registration.

John F. McCarthyVice President for Scientific and Regulatory AffairsNational Agricultural Chemicals Association, 1989

“Exporting banned pesticides demonstrates that from the cradle to the grave---or from production to use anddisposal--dangerous chemicals are discharged into our environment, and threaten the public health both hereand abroad. ”

Sandra MarquardtExporting Banned Pesticides: Fueling the Circle of Poison

Greenpeace USA, 1989

CONTENTSPage

INTERNATIONAL REGULATORY ACTIVITIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . + + .U.S. Regulation of Neurotoxic Substances . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .International Effects of U.S. Export Practices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Regulatory Policies in Other Industrialized Nations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Regulatory Issues in Developing Nations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

INTERNATIONAL NEUROTOXICOLOGICAL RESEARCH . . . . . . . . . . . . . . . . . . . . .Major Directions of Academic, Industrial and Government Research . . . . . . . . . . . . . .Neuroepidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . .. .. .. .* .. .. .. .. ..+. . . . . . . . . . . . . .International Cooperation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Comparison of U.S. and Foreign Research Programs . . . . . . . . . . .. .. . ... ... ...+....Resources . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Future Directions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Foreign Governments Likely To Take Leadership Roles . . . . . . . . . . . . . . . . . . . . . . . . . .

SUMMARY AND CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .CHAPTER PREFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. .. .. .. $.. ... .......+

Box9-A.9-B.

Problems With Neurotoxic Pesticides

Boxes

237239242245248256256259259259259259260260261

Pagein Developing Countries . . . . . . . . . . . . . . . . . 251

Incident at Lake Volta. Ghana .. .. .. .. .. ... ... ~..._... . . . . . . . . . . . . . . . . . . . . . . . . . 252

FiguresFigure Page9-1. Total U.S. Pesticide Exports, 1983-88 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ● . . . . . . 2379-2. U.S, and World Pesticide Sales . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2379-3. Total U.S. Food Imports, 1983-88 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2399-4.9-5.

Domestic Production v. Imports of Selected Major Crops . . . . . . . . . . . . . . . . . . . . . . . 239Pictograms for Agrochemical Pesticides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 244

Table9-1. Neurotoxic Substances Investigated in Papers Published

Journals, by Country, 1979-87 . . . . . . . . . . . . . . . . . . . . . .9-2. Subjects of Neurotoxicological Research Presented at a Major

International Conference . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 258

Pagein Two International

. . . . . . . . . . . . . . . . . . . . . . . . . 258

Chapter 9

International Regulatory and Research Activities

This chapter examines the international regula-tory and research programs devoted to neurotoxicsubstances in general and neurotoxic pesticides inparticular. The first part of the chapter addresses theexport of neurotoxic pesticides that have beenbanned or severely restricted (a limited ban) in theUnited States. Regulatory programs in foreigncountries, both industrialized nations and develop-ing nations, are discussed. The second part of thechapter focuses on international research activities.This chapter does not address the export of foodadditives, drugs, and other chemicals.

INTERNATIONAL REGULATORYACTIVITIES

According to the U.S. General Accounting Office(GAO), from 1977 to 1987, the worldwide agricul-tural chemical market doubled in size, to morethan $17 billion. U.S. pesticide export salescurrently represent approximately one-quarterof the world pesticide market. Although U.S.export statistics vary, the best estimates concludethat about 400 to 600 million pounds of U.S.-manufactured pesticides are exported each yearto foreign countries. According to GAO, unregis-tered pesticides, including banned or restrictedpesticides as well as pesticides that may neverhave sought U.S. registration, now account forabout 25 percent of all U.S. pesticide exports (61).

7.5

7.0

6.5

6.0

5.5

5.0

4.5

Figure 9-l—Total U.S. Pesticide Exports, 1983-88

Billions of dollars

4.8

m1983

6.3

7

1984 1985 1986 1987 1988

SOURCE: Office of Technology Assessment, 1990, based on U.S. Depart-ment of Commerce, Bureau of the Census, Statistical Abstractof the United States 1989, 109th ed. (Washington, DC: 1989).

According to other estimates, the United Statessupplies approximately one-half of the pesticidesimported in most Latin American countries,where a substantial amount of the fresh fruits andvegetables eaten in the United States in the wintermonths are grown (42). Figure 9-1 illustrates U.S.pesticide exports for 1983 to 1988. In recent years,approximately 50,000 different pesticide productshave been registered for use by the EnvironmentalProtection Agency (EPA) (61). This figure does notinclude pesticides that have never been registeredbut are manufactured and exported for use outsidethe United States. Figure 9-2 compares U.S. pesti-cide sales with world pesticide sales for 1987.

Some developing nations have few or no regula-tions to protect workers and consumers from theharmful effects of neurotoxic substances. Develop-ing nations that do have regulations often do nothave adequate resources to implement and enforcethem. This lack of effective regulation and enforce-

Figure 9-2—U.S. and World Pesticide Sales(Basic Producer Level, 1987)

20 Billions of dollars1

18+

16

14

12

i

1 0

8

6

4[

JzLHerbicides Insecticides Fungicides Other Total

Iz2 Us. = World

SOURCE: Pesticide Industry Sales and Usage: 1987 Market Estimates,Economic Analysis Branch, Biological and Economic AnalysisDivision, Office of Pesticide Programs, Environmental Protec-tion Agency, Washington, DC, September 1988.

238 ● Neurotoxicity: Identifying and Controlling Poisons of the Nervous System

ment in developing nations has a negative impact notonly on the public health and environment in usercountries, but also in industrialized nations, includ-ing the United States, where people process andconsume imported crops that may contain pesticideresidues.

Despite many regulations promulgated in thiscountry for the protection of consumers and workers,U.S. citizens are exposed to banned and severelyrestricted pesticides through what has come to bereferred to by critics as the ‘‘boomerang effect’ orthe “circle of poison” (41,70). At times, food inU.S. supermarkets has been imported from develop-ing countries where farmers use pesticides manufac-

.’-”. ‘<

. . \ ‘ . .. “ - . \“ ---

Illustrated by: Ray Driver

tured in the U.S. that have been banned, severelyrestricted, or never registered for use here. Figure 9-3indicates the dollar value of total U.S. food importsfrom 1983 to 1988. One organization has estimatedthat 70 percent of the pesticides exported to develop-ing countries are used on crops grown for export toindustrialized countries (70). This effectively cir-cumvents the protection that the regulatory actionwas intended to provide.

Federal law currently permits U.S. companies tomanufacture and distribute banned, severely re-stricted, and never registered pesticides for use indeveloping nations, despite the possibility that foodproducts containing residues of these pesticides maybe imported to the United States and made availableto U.S. consumers. Little definitive informationexists on the identity and quantity of residues ofbanned, severely restricted, and never registeredpesticides that return to the United States onimported crops and meats. This is due in part to therelatively small number of Food and Drug Adminis-tration (FDA) and U.S. Department of Agriculture(USDA) personnel available to screen sufficientquantities of imported crops and to limitations in thetechnology for detecting residues (62). However,data are available on the dollar value of crops that areproduced domestically versus the value of crops thatare imported. Figure 9-4 compares domestic produc-tion with imports of selected major crops. Somecrops, such as coffee, are not produced domestically,so the United States must depend entirely on importsto supply consumer demand.

One example of the effect of current policies is theexport of the insecticide chlordane. This product wastaken off the U.S. agrichemical market in 1978 dueto concerns about its carcinogenicity (it is alsoneurotoxic) and its persistence in animal fatty tissueand in the environment. Yet Federal law allows it tobe manufactured and exported, without prior notifi-cation, to developing countries which do not have toadhere to U.S. use controls. Chlordane and hep-tachlor export formulations were both registeredunder section 3 of the Federal Insecticide, Fungi-cide, and Rodenticide Act (FIFRA) and as such areexempt from the export notification requirementsimposed by language in section 17 of FIFRA. Atleast twice in 1988, adulterated beef from Honduras,contaminated with chlordane, was imported into theUnited States and consumed by people in Florida,Kentucky, and Minnesota before the contaminationwas discovered (33,54). In one such instance, the

Chapter 9-International Regulatory and Research Activities ● 239

Figure 9-3-Total U.S. Food Imports, 1983-88

Millions of pounds

aoo~

4 0 0 -

2 0 0 -

414

1983

527

1984

598

492

1986

507

.

550

1987 1988

SOURCE: Office of Technology Assessment, 1990, based on U.S. Depart-ment of Commerial-, Bureau of the Census, Statistical Abstractof the United States 1989, 109th ed. (Washington, DC: 1989).

Figure 9-4-Domestic Production v. Importsof Selected Major Crops

Billions of dollars3.5

3.0

2.5

2.0

1.5

1.0

0.5

0

1,8s

Tobacco Olives Bananas Pine- Straw- Coffee Tomatoesapples berries

_ Domestic production [“’”~ Imports

SOURCE: Office of Technology Assessment, 1990, based on U.S. Depart-ment of Commerce, Bureau of the Census, Statistic/Abstractof the United States 1989, 109th ed. (Washington, DC: 1989).

chlordane residue was reported to be eight times theapproved tolerance (33). Chlordane has been bannedfor all agricultural use in the United States yet iswidely used in agricultural settings in countries suchas Argentina, Australia, Colombia, and the Domini-can Republic (33). In some cases, residues are notthe result of direct application to crops or livestock.The Honduran problem was attributed to the use ofchlordane on nearby sugarcane.

The misuse of registered chemicals, many of themneurotoxic, is an equally important issue (38).

Registered chemicals used by untrained farmwork-ers without proper protective clothing and equip-ment, in inappropriate amounts on inappropriatecrops, and without attention to other safety regula-tions, have been known to cause significant publichealth and environmental problems. Moreover, asubstantial proportion of all pesticides are used todestroy pests that primarily affect the appearance ofagricultural crops. Consumers often demand thattheir fruits and vegetables look “picture perfect”;however, cosmetic imperfections usually do notaffect either the taste or the nutritional value of mostfoods (22). Although limited use of less hazardouspesticides is generally considered to be economi-cally beneficial and to pose a minimal health risk,overuse of the more hazardous pesticides is anincreasing concern among public health officialsworldwide.

U.S. Regulation of Neurotoxic Substances

Export Laws

The United States has several laws governingexport of toxic substances. The Toxic SubstancesControl Act (TSCA) was enacted in 1976 to addressthe risks presented by hazardous chemicals and isthe primary statute regulating the export of industrialchemicals. Section 12 of TSCA addresses exporta-tion of hazardous chemicals. Section 3017 of theResource Conservation and Recovery Act (RCRA)discusses the export of hazardous waste, and section17 of FIFRA governs importation and exportation ofpesticides and devices.

Under TSCA, chemicals for domestic use thatpresent an unreasonable risk of injury to humans andare imminent hazards to the environment can beregulated. The Act requires that regulation be donein such a way as not to impede unduly or createunnecessary economic barriers to technologicalinnovation. Section 12 provides that, in mostinstances, the requirements of TSCA do notapply to substances manufactured, processed, ordistributed for export. The requirements willapply, however, if it is determined that thesubstance, mixture, or article will present anunreasonable risk of injury to the health ofpersons within the United States or to theenvironment of the United States. The Act alsoprovides that any person who exports or intends toexport a substance for which submission of data isrequired under this Act must notify the Administra-

240 . Neurotoxicity: Identifying and Controlling Poisons of the Nervous System

tor of the Environmental Protection Agency of theexportation or intent to export. Moreover, theAdministrator shall then furnish to the governmentof the importing country notice of the availability ofthe data submitted for each substance.

RCRA provides for the management and disposalof solid wastes to avoid contamination of theenvironment. Section 3017 prohibits any exportingof hazardous waste unless the importing country hasbeen given notice of and has consented to theshipment of the waste. However, exporters are notrequired to describe the contents or toxicity of thewaste they are shipping. In addition, incinerator ashand municipal waste, both of which contain neuro-toxic metals and chemicals, are not covered by theconsent scheme.

Section 17 of FIFRA states that pesticides anddevices intended solely for export are exempt fromthe testing and review requirements of the Act.Accordingly, pesticide manufacturers and dis-tributors can legally export pesticides that havebeen banned or never registered for use in thiscountry. Little is known about pesticides that havenever been registered because they are exempt frompublic health and environmental testing require-ments if domestic use is not intended (32).

U.S. pesticide manufacturers are required tonotify the importing purchaser, and EPA notifies thecountry, if the pesticide to be exported has beenbanned or never registered for use in the UnitedStates. EPA requires these statements annually forthe first shipment of each banned or unregisteredproduct to a particular purchaser for each importingcountry. Although EPA has streamlined the trans-mittal process for export notices to U.S. embassies,no formal procedures govern the processing andtransmittal of FIFRA notices once they arrive at anembassy (61). Most embassies destroy files as recentas 1985, and staff at every embassy surveyed byGAO indicated that they sometimes do not retaincopies when transmitting files to the foreign govern-ments (61 ). According to GAO, as recently as 1988,EPA had no program to determine whetherpesticide manufacturers were complying with theexport notification requirements and had noassurance that importing countries were ade-quately notified of unregistered U.S. pesticidesentering their borders (61 ). Moreover, shipment ofthe unregistered pesticide may proceed before the

foreign government has received the notice, since itspurpose is only informational.

Although the language in section 17(a) of FIFRAgoverning notification requirements for unregisteredpesticides provides for no exceptions, EPA, in 1980,established a policy that effectively waives notifica-tion requirements for unregistered pesticides that are“minor variations” on formulations and activeingredients registered in the United States and thatare ‘‘similar in composition and use” to registeredpesticides. These exempted pesticides are com-monly referred to as “me-toos.” Thus, never-registered pesticides must bear the statement “NotRegistered for Use in the United States of America’when they are exported to foreign markets, butme-toos are exempt from the labeling requirement,despite the fact that the active ingredient and inertingredient formulation may be different from thatregistered in the United States and thus pose adifferent risk (32). Accordingly, it would be difficultfor an importing foreign purchaser or nation to knowthe degree of hazard of such a product. Moreover,GAO determined that EPA did not send requirednotices for three of four pesticides, despite the factthat they were voluntarily canceled because ofconcern about toxic effects (42). Although EPAfinalized cancellations of these four pesticidesbetween 1975 and 1987, a notice was issued on onlyone of them (42). Consequently, foreign govern-ments may not be alerted to unreasonable hazardsassociated with using particular pesticides.

Section 17(b) of FIFRA requires that EPA notifyforeign governments and appropriate internationalagencies “[whenever a registration, or a cancella-tion or suspension of the registration of a pesticidebecomes effective, or ceases to be effective. . . .“EPA has no regulation or formal policy statement onwhen to issue such a notice. Instead, the Agencyissues notices for cancellations and suspensions itdeems to be of “national or international signifi-cance” (42). EPA periodically publishes a bookletsummarizing and clarifying its actions on canceled,suspended, and restricted pesticides (67); however,this booklet was last published in 1985. If updatedannually, this booklet could be used by foreigngovernments and others as a reference guide to U.S.regulatory actions on pesticides (42).

On January 15, 1981, several days before the endof his term, President Jimmy Carter issued Execu-tive Order No. 12264, “On Federal Policy Regard-

Chapter 9-international Regulatory and Research Activities ● 241

ing the Export of Banned or Significantly RestrictedSubstances,’ including pesticides. This order putcontrols on exports of substances that were bannedor severely restricted in the United States. Severaldays after becoming President, Ronald Reaganrevoked the order.

Regulation of Pesticide Residues inDomestic and Imported Food

Federal jurisdiction over pesticide residues infood is divided among three agencies—EPA, FDA,and USDA. Their authority derives primarily fromfive laws: FIFRA; Federal Food, Drug, and Cos-metic Act (FFDCA); Federal Meat Inspection Act(FMIA); Poultry Products Inspection Act (PPIA);and Egg Products Inspection Act (EPIA) (62).

Under FIFRA, a pesticide must be registered(even conditionally) or have its registration pendingbefore it can be used in the United States. Inregistering a pesticide, EPA considers the results ofnumerous public health and environmental fatestudies (submitted by the manufacturer) to deter-mine the risks and benefits associated with the useof that pesticide. Registration includes identificationof the specific commodities on which the pesticidecan be used. During the registration process, EPAattempts to determine if the pesticide’s use willcause an unreasonable risk to humans or theenvironment (see ch. 7). The registration require-ments for pesticides are set forth in section 3 ofFIFRA and are defined more fully in EPA regula-tions (40 CFR 1987 ed. 158, 162).

If use of a pesticide will leave a residue on foodor feed commodities, EPA, under FFDCA, estab-lishes a legal maximum level, or “tolerance,” forthe pesticide residue. A tolerance, or an exemptionfrom a tolerance, must be granted before a pesticideis registered. Tolerances cannot be legally exceeded,and residues of pesticides for which no tolerance hasbeen established or exempted are prohibited onfoods. Commodities that violate these prohibitionsare subject to seizure by FDA, USDA, or a Stateenforcement agency (62).

If a pesticide has never been registered for use inthe United States and the manufacturer does notexpect residues to occur on imported foods, atolerance will not necessarily have been set. Also,tolerances may not have been established if a

Photo credit: Michael Hansen

registration application is pending. Any importedfood contaminated with a pesticide that does nothave a tolerance is considered adulterated and issubject to seizure at the U.S. border. However, ifUSDA and FDA border inspectors are not told thatthese pesticides have been used or they are unable totest for them, illegal residues in imported food willnot necessarily be detected.

One pesticide industry spokesman has indicatedthat increased monitoring for pesticide residueswould strengthen and bolster U.S. consumer confi-dence in the quality of the food supply (35).Additional testing of agricultural chemicals, called‘‘reregistration, ‘‘ is under way, and over the next 9years, the agricultural chemical industry expects topay $170 million in fees to help EPA finance theeffort (35).

FDA, under FFDCA, is responsible for enforcingtolerances established by EPA for food and animalfeed in interstate commerce. It is also responsible forenforcing the prohibition in food or animal feed ofresidues of pesticides for which no tolerance hasbeen set or exemption given. In the past, when FDAconsidered low levels of a residue to pose little riskto human health, it would set informal residue levels,called action levels. At these levels, FDA wouldtake regulatory action; below them the food wasconsidered safe. A recent court opinion struck down


this practice, and EPA and FDA are currentlydetermining how to address this issue.1

The USDA is responsible for enforcing tolerancesin meat and poultry under authority of the FederalMeat Inspection Act and the Poultry ProductsInspection Act. It is also responsible for monitoringpesticide residues in raw egg products (dried, frozen,or liquid eggs) and for enforcing tolerances atestablishments having official USDA egg productsinspection services, under authority of the EggProducts Inspection Act (62). While most of thefocus has been on food crops, more insecticide isused on cotton on a worldwide basis than any othercrop (23).

International Effects of U.S.Export Practices

Regulations governing the export and import ofneurotoxic substances are far from uniform. Manynations, including the United States, have policiesand procedures in place, but too often they work onlyon paper. In practice, they may allow neurotoxicsubstances to slip through the regulatory cracks.Regulatory requirements designed to protect work-ers and consumers from the harmful effects of toxicsubstances may be ineffective in some countries.The United Nations Food and Agriculture Organiza-tion (FAO) has implemented an International Codeof Conduct on the Distribution and Use of Pesticidesto outline responsible behavior on the part of personswho deal with pesticides. Pesticides are known asthe group of chemical products that includes insecti-cides, acaricides, molluscicides, rodenticides, ne-maticides, anthelmintics, fungicides, and herbicides(26). Although many consider the code a step in theright direction in terms of providing notification,use, and transport protections (among others), it isonly a voluntary code, and FAO has no enforcementauthority. The objectives of the code are to set forthstandards of conduct for all entities engaged indistributing and using pesticides. Pesticides arebiologically active, and their uncontrolled releasewill always present a potential threat to the environ-ment (27). The code describes the shared responsi-bility of many segments of society, government,industry, trade, and international institutions to usepesticides when necessary without adversely affect-ing people or the environment (40).

The Pesticide Development and Safe Use Unit ofthe International Program on Chemical Safety hastoxicologically evaluated 83 pesticides widely usedin agriculture and public health and establishedaverage daily intake and maximum residue limits for23 of them (43). The Codex Alimentarius Commis-sion (Codex) has established maximum residuetolerances for numerous chemical residues, contam-inants, and food additives (43). Sampling andanalysis principles to determine pesticide residues infood and animal feed have also been developed (43).

Despite numerous regulations governing the ex-port and import of pesticides and other neurotoxicproducts in the United States and abroad, somecountries do not have the regulatory framework andresources to adequately protect human health andthe environment from these substances. Nearly allmajor U.S. corporations producing pesticidesthat have been banned, severely restricted, ornever registered for use in the United States aremultinational and have subsidiaries or otherdistributors in developing countries. In somecases it is through these subsidiaries and distribu-tors that such pesticides are imported and dis-tributed in developing countries. This also allowscorporations with stocks of toxic substances thatcan no longer be sold in the United States to sellexisting products.

In addition to concern about food products that areimported into the United States with residues ofbanned, severely restricted, or unregistered pesti-cides, critics are concerned that exported pesticidesmay not be properly packaged or labeled. At times,the package labeling and instructions may be writtenin English instead of the native language of theimporting country. In some cases, farmworkersusing the pesticides are illiterate and thus could notread the labels even if they were written in theirnative language.

Improper labeling may prevent implementation ofappropriate safety measures or precautions by farm-workers and consumers. In July 1986, phosdrin, apotent neurotoxic insecticide classified by the WorldHealth Organization (WHO) as “extremely hazard-ous, ” was purchased in Benguet Province, Philip-pines. The product label had seven labeling infringe-ments, all of them in direct violation of the FAOcode (20). Similar violations of the FAO code have

ISCX 21 cm WCS. 109 and 509, 1987; FDA Compliance Policy Guides, 1986. The informal process by which these action levels wem set wu vac~~by the Federal Appeals Court in the District of Columbia Consumer Nutrition institute v. Young, 818 F.2d 943 (D.C. Cir. 1987).


been discovered recently in Ecuador, Papua NewGuinea, Thailand, Senegal, Colombia, South Korea,Sudan, and Mexico (18). In Iraq in 1973, anepidemic of methyl mercury poisoning resulted fromimproper labeling. Farmers and their families atebread made from seed treated with mercury. Thebags in which the grain was imported were clearlylabeled in English and Spanish (neither of which isa native language of Iraq). More than 1,000 peopledied from mercury poisoning, and 10 times morewere hospitalized (see box 2-A, in ch. 2) (2).

In some instances, even if the pesticide is properlypackaged and labeled when it leaves the exportingcountry, it is repackaged in the importing countrywithout the necessary labeling. Accordingly, thepesticide product that actually reaches the user maylack very important health and safety information.Repackaging is frequent, because pesticides areoften shipped in 35- to 100-gallon drums and arethen transferred into smaller, more manageable sizesfor the consumer. On an international scale, pesti-cides are widely available to the general public, andfew warnings are given (18). In some countries,pesticides are sold in markets alongside vegetablesand grains. People can scoop up pesticides incartons, bottles, cans, plastic or paper bags—whatever they bring to the market. Often they do notknow the name of the chemical they are purchasingbecause the container is not labeled. In somecountries, pesticides are marketed as ‘‘plant medi-cines, " and farmers are encouraged to use them tokeep their crops healthy in much the same way thatmedicines are used to keep people healthy (24).

The pesticide industry is aware of the illiteracyproblem and is taking steps to circumvent it. Oneapproach is to use illustrations, or ‘‘pictograms, ’that convey to an illiterate worker the appropriateway to mix, use, store, or clean up pesticides. Thesepictograms were designed by the InternationalGroup of National Associations of Manufacturers ofAgrochemical Products, an international consortiumof pesticide manufacturers, formulators, and distrib-utors, in cooperation with the FAO. Figure 9-5shows examples of pictograms currently used bysome pesticide companies in developing countries.It is not yet known how extensively the pictogramsare used or with what degree of success.

It is not only in export and use that pesticides poseproblems, however. Pesticides are frequently manu-factured in developing countries, where there are

less stringent regulations. U.S. manufacturers claimthat it is safer to produce pesticides in the UnitedStates, with its many regulations, than in developingcountries. The combination of lethal ingredients anddeficient safety precautions was dramatically dem-onstrated by the 1984 leak at the Union Carbidepesticide plant in Bhopal, India, which killed morethan 2,000 people and injured tens of thousands (69).

Pesticide manufacturers justify U.S. export prac-tices and advocate increased use of pesticides bymaintaining that developing nations need pesticidesto combat famine. The world population is growingrapidly: in 1975 it was 4.1 billion; in 1987 it hadgrown to 5,1 billion; and the projected figure for2005 is 6.7 billion (64). Feeding this ever-increasingpopulation is a problem because land available forfarming is not increasing significantly. Moreover,the population increase is greatest in developingnations.

Critics of U.S. export practices argue that pesti-cides in the developing world are more often appliedto luxury export crops than to staples eaten by localinhabitants and that, in any case, nonchemicalmethods of pest control could and should beimplemented (70). According to the World Bank, theworld produces enough grain alone to provide everyhuman being on the planet with 3,600 calories a day(72). In a major 1986 study of world hunger, it foundthat a rapid increase in food production does notnecessarily result in less hunger. Hunger can only bealleviated by redistributing purchasing power andresources to those who are undernourished (72). InIndia, for example, despite a 24-million-ton grainsurplus (25), per-capita consumption of grain has notincreased in 20 years and nearly half the populationlacks the income necessary to buy a nutritious diet(63). Availability of grain in India has actuallydeclined in recent years, despite a rise in pesticideuse (57). Furthermore, numerous plantations andother agricultural areas have been forced to turnaway from pesticide use due to resistance problemsdeveloped by insects, weeds, and fungi overdosedwith pesticides (23).

The USDA has addressed the issue of worldhunger, particularly in developing nations, as fol-lows:

First, the food problem of the developing coun-tries is not a global lack of food. More than enoughfood is produced and stored in the world to provide

244 ● Neurotoxicity: ldentifying and Controlling Poisons of the Nervous System

Figure 9-5-Pictograms for Agrochemical Pesticides

Storagepictogram

Activitypictograms

Keep lockedaway andout of reachof children

Handlingliquidconcentrate

\

\ n

Handling

b

ApplicationdryConcentrate

:.... ..... . .

w %

,,:.,,., ,..,,,, ,.,, ,. , $ ., , . .

Weargloves

Advicepictograms

Wearboots

Warningpictograms

Dangerous/harmful toanimals

Wearprotectionover noseand mouth

Dangerous/harmful tofish–do notcontaminatelakes, rivers,ponds,orstreams

Wearrespirator

SOURCE: International Group of National Associations of Manufacturers of Agricultural Products, 1988 Pictograms for Agrochemical Labels: An Aid to theSafe Handling of Pesticides.


people everywhere with adequate diets. In times ofcrises, countries have the capacity to respond quicklywith food and other needed supplies to alleviatehunger and suffering. Unfortunately, political differ-ences within and between countries and logisticssometimes impede the efforts to save lives, as in thecurrent food crisis in sub-Saharan Africa (59).

Regulatory Policies in OtherIndustrialized Nations

For the most part, regulations in industrializedcountries are enforced, and public health and envi-ronmental problems from pesticide importation,distribution, and use are not as severe as in develop-ing nations. However, this does not mean thatpesticide problems are nonexistent in industrializednations. The following discussion summarizes theactivities of some industrialized nations with majorregulatory programs.

Canada

Within Canada primary responsibility for envi-ronmental issues with international and interprovin-cial components lies with the federal government,while the provinces are generally responsible forenforcing regulations governing industries withintheir borders (12). Environment Canada, establishedin 1971, is the federal department that administerslegislation relating to environmental protection. Amajor reorganization of Environment Canada in1986 and 1987 consolidated the department’s activi-ties into three main branches: Conservation andProtection, Atmospheric Environment (responsiblefor meteorology), and Parks (responsible for mainte-nance of national parks). Conservation and Protec-tion includes the Canadian Wildlife Service, Environ-mental Protection, and the Inland Waters and LandsDirectorate.

The primary federal legislation controlling theavailability, sale, and use of pesticides is the PestControl Products Act, administered by AgricultureCanada (12). The Act requires annual registration ofpesticides and prohibits import or sale of unregis-tered pesticides. It is intended to ensure that noperson shall use a pesticide under conditions that areunsafe to human or animal health or that willadversely affect the environment. The Act alsorequires that such products be effective for theirintended purposes (46). There are currently plans toupgrade the legislation to require more stringenttesting of pesticide products.

Agriculture Canada calls on various federal de-partments to provide expert advice on hazards thatmay be associated with the use of a product. Healthand Welfare Canada requires and reviews a range oftoxicological studies to assess potential healthhazards that may be associated with exposure to achemical, including acute, subacute, chronic, repro-duction, teratology, and metabolism studies. Inaddition, studies to estimate anticipated humanexposure during typical field use of the chemical arerequired.

The federal departments primarily involved in thepesticide review process are Agriculture Canada,Fisheries and Oceans Canada, Environment Canada,and Health and Welfare Canada (12). The PesticidesDirectorate of Agriculture Canada receives themanufacturer’s application for registration of thepesticide and is responsible for the evaluationprocess and the coordination of reviews from theother agencies (46).

Federal Republic of Germany

The Federal Republic of Germany, one of theworld’s largest exporters of pesticides, divides andsometimes shares lawmaking and enforcement pow-ers between the federal government (Bund) and the11 states (Lander). The Federal Ministry for Envi-ronment, Nature Protection, and Nuclear Safety wascreated in 1986, in the aftermath of the accident atthe nuclear power plant in Chernobyl in the SovietUnion. It was created out of the Environment andNuclear Safety divisions of the Ministry of Interiorand the Nature Protection Division of the Ministryof Nutrition, Agriculture, and Forest (MNAF) (14).

Pesticides are regulated under the Pfalnzen-schutgesetz (Plant Protection Law), which outlinesthe terms of licensing, prohibition, or restriction ofuse, application, and export (43). Licensing, whichis issued only if the pesticide is safe, efficacious, andin compliance with requirements for human andanimal health and safety, provides for classification,testing, labeling, and packaging (43).

The Federal Environmental Agency (FEA), underthe authority of the MNAF, is responsible forgeneral environmental policy-related research, in-cluding maintenance of an environmental informa-tion planning system, collection of informationnecessary to develop and implement federal laws,and preparation of legislation and administrativeregulations. The FEA has done considerable work


on the development of environmental impact assess-ment procedures (14). A separate organization, theConference of State Ministers for the Environment,which includes the Federal Environment Ministry, isthe major forum for coordination of state and federalenvironmental policy. Federal-state working com-mittees have been established to coordinate pro-grams in all major areas of environmental protection(14).

The Federal Ministry for Foreign Affairs isresponsible for international relations and environ-mental policy. The Federal Ministry of Food,Agriculture, and Forestry houses the AgriculturalResearch Center, which monitors soil biology,agrichemicals, agricultural waste recycling, plantecophysiology, and water pollution, and the FederalCenter for Biological Research in Agriculture andForestry, which is responsible for pesticide measure-ment and control, biological pest control, andinspection of commercial chemical preparations forplant protection and pest control (14).

A number of environmental laws are in effect. TheAct on Protection Against Dangerous Substances,which was adopted in 1980 and amended in 1986,establishes a testing and notification system for newchemical substances placed on the market afterSeptember 1981. The Act seeks to protect publichealth and the environment from harmful effects ofdangerous substances by: 1) compulsory testing ofand notification regarding substances; 2) compul-sory classification, labeling, and packaging of dan-gerous substances and preparations; 3) prohibitionsand restrictions on use; and 4) specific legalprovisions concerning toxicity and occupationalsafety. The Act covers foodstuffs, tobacco products,cosmetic agents, animal feedstuffs and additives,pharmaceuticals, wastes, radioactive wastes, wastewater, and waste oils (14).

The Act requires notification at least 45 days priorto placing a substance into initial circulation in acountry that is a member of the European Commu-nity (EC), whether on a commercial basis or withinthe framework of any other business undertaking.There is no requirement for notification if thesubstance was manufactured and notified by anequivalent procedure in any other EC membercountry (14). Six administrative regulations havebeen adopted concerning information required innotifications, designation of the Federal Office foroccupational and Safety Policy to receive notifica-

tions, inventory of existing chemical substances,labeling of hazardous substances, and general ad-ministrative procedures.

Criminal violations of environmental legislationare generally codified in division 28 of the criminalcode, adopted in 1975 and last amended in 1987.Penalties range from fines to jail sentences and areusually defined in the particular environmental law(14).

Belgium

Environmental programs in Belgium are less welldeveloped than those in other European countries.Because implementing legislation must, in mostinstances, be enacted by the regional administra-tions, norms and enforcement vary throughout thecountry (11).

A 1969 act regulates the manufacture, composi-tion, storage, transport, and marketing of pesticides.Such activities may be carried out only by licensedpersons. The maximum concentrations of residueafter decomposition may also be controlled underthe act, as well as the conditions of use of pesticides.Pesticides themselves are subject to an approvalprocedure, and the license usually lasts for 10 years.The approval is made subject to conditions, and it isan offense to use pesticides other than in accordancewith these conditions (1 1).

A royal order of 1975 regulates the storage, trade,and use of pesticides and plant protection products.Pesticides are subject to premarket registration, andcertain labeling and packaging requirements are setout (11). A royal decree of 1977 implements ECDirective 76/1 16, which prohibits the marketing ofmanure and fertilize, as well as all products with aspecific action to stimulate crop production. Thisdecree also regulates the information and indicationsto be put on the package, the documents required fortransport, the packaging requirements, and themethod of taking and analyzing samples (11).

A royal decree of 1982 requires that beforeplacing a dangerous substance on the market, anymanufacturer or importer must submit to the Minis-ter of Public Health a dossier that includes adeclaration of the unfavorable effects of the sub-stance for the various uses envisaged. The decreeestablishes a Committee on Dangerous Substances,composed of officials of different ministerial depart-ments and attached to the Ministry of Public Health.The committee is responsible for examining the


notification procedure and advises on the complete-ness of the application. A dangerous substancecannot be placed on the market during the 45 days ittakes to complete the notification procedure (1 1).

France

Pesticides for agricultural use are governed by a1972 law that controls manufacture, sale, and use aswell as packaging and labeling (43). Prior toapproval for production, toxicity and efficacy mustbe assessed, and the pesticide must be classified interms of toxicity (43). Tolerance limits in foods areprescribed by presidential decree (43).

The Chemicals Control Law, adopted in 1977,governs hazardous substances. It is intended toprotect public health and the environment againstrisks that may arise from natural or industriallyproduced chemicals, but it does not apply tochemicals used in research or to food additives,cosmetics, or drugs (13). The law provides forpremanufacture notification for all chemicals thathave not yet been marketed. Producers or importersmust declare any new risk that may result from achange of manufacturing process or from emissionof the said chemical into the environment (37).

Producers or importers of new chemicals mustalso submit a technical dossier providing the infor-mation needed for assessment of potential hazards.The competent authority may classify a substance asa “dangerous product’ request from the manufac-turer or importer any relevant information withrespect to potential health or environmental effects;and prohibit or restrict the production, composition,storage, transportation, conditioning, labeling, mar-keting, use, or disposal of any chemical wheredeemed necessary to protect the public (37).

Producers of already marketed substances mayberequired to provide public authorities with appropri-ate technical or toxicological data to evaluatepotential health or environmental risks. Violation ofthe law may result in imprisonment or fines or both.

Japan

Agricultural chemicals are regulated by a 1948law that has been amended several times, mostrecently in 1983 (43). It requires that pesticides beregistered with appropriate government agencies,which classify pesticides according to persistence incrops and soil and water pollution potential (43).Limits are placed on the amount of active ingredi-

ents and the maximum allowable harmful ingredi-ents for each pesticide (43). The applicant mustprovide test results on pesticide effectiveness, toxic-ity, phytotoxicity, and persistence (43). Labelingand packaging must represent truthfully all state-ments and facts on which the pesticide was regis-tered and must include, among other things, thedangers posed and precautions to be taken forstorage and use (43).

Other toxic substances are regulated by theChemical Substances Control Law of 1973. Theneed for comprehensive measures to prevent envi-ronmental pollution has been recognized followingenvironmental crises such as the mercury poisoningincident at Minamata Bay in the 1950s (see ch. 2).

The law requires notification and testing of allnew chemical substances produced in quantitiesexceeding 100 kilograms. The law does not apply tochemicals in use before the law came into effect, butan agreement reached in the Diet makes some 800existing chemicals subject to the same reviewstandards as the new substances. The law alsoprovides that, prior to production or importation, allnew chemicals must be submitted to official exami-nation regarding persistence, accumulative ten-dency, and toxicity to human beings.

A substance may be classified as a “specifiedchemical substance” if it accumulates easily inbiological organisms, if it resists chemical changescaused by natural effects, and if it may harm humanhealth when ingested over a period of time. The lawwas passed in response to polychlorinated biphenyl(PCB) poisoning (9). Chemicals tested and desig-nated ‘‘specific substances’ are subject to prohibi-tion or restriction. Although only PCBs have beenformally listed as specific substances under the law,government officials say that two or three chemicalsare withdrawn from testing every month whenmanufacturers learn that the chemicals probablywould be specified and the manufacturer’s namerevealed. Another two or three applications forapproval are suspended each month for lack of data(9).

The Pollution-Related Health Damage Compen-sation Law of 1974 was further modified, in the caseof Minamata victims, by the Minamata Relief Lawin 1978. The beneficiaries of this law are the victimsof certain pollution-related diseases who have ‘lived,worked, or otherwise been present” in designatedareas. Testing for functional developmental disor-


ders, including behavior disorders, has become oneof the most important aspects of the evaluation ofdevelopmental toxicity of chemicals, especiallypharmaceutical drugs. There are two guidelines fordevelopmental toxicity testing of chemicals-one athree-segment study for drugs, the other a multigen-eration study plus embryotoxicity for environmentalchemicals (56). In the case of specific diseases,where the source of pollution is known, the companyresponsible must pay compensation. In nonspecificcases, there is a levy on polluting industries to coverclaims. Certified victims, that is, persons who havebeen examined by government medical panels, areentitled to medical care expenses and a monthlyphysical handicap payment, the amount being deter-mined by the victim’s age, sex, and ability to work.There are also child compensation allowances andsurvivors’ benefits. Payment is made by localgovernments through the Pollution-Related HealthDamage Compensation Association. The govern-ment covers the association’s overhead costs, butpayments to victims are financed by polluters.

United Kingdom

Pesticides are regulated under the DangerousSubstances Regulations and the Food and Environ-ment Protection Act (43). The regulations specifywhich toxicity tests are necessary to categorize eachpesticide, based on EC Directive 78/631 of 1978(43). Packaging and labeling requirements are alsoset out in the regulations (43). Pesticide manufactur-ers must notify the government prior to marketing anew pesticide or suggesting new uses of an old one(43). Manufacturers must also provide sufficientdata to enable government assessment of pesticidedangers, and warnings, precautions, and names ofactive ingredients must be included on all labels(43). The government has authority to requestwithdrawal of unsafe products and to specify maxi-mum pesticide residues on crops, foods, and live-stock feed (43).

Responsibility for protection of the environmentlies primarily with the Department of the Environ-ment. It has responsibility for introducing andimplementing acts of Parliament and statutoryinstruments. Other ministries also have some re-sponsibility for environmental protection. Theseinclude the Ministry of Agriculture, Fisheries, andFood, which controls the ocean disposal of wastesand has joint responsibility with the Department ofthe Environment and the Welsh Office for control of

radioactive discharges from nuclear sites; the De-partment of Employment, which is responsible forhealth and safety; the Department of Health andSocial Security; and the Department of Transport.Within the Department of the Environment is theCentral Directorate on Environmental Pollution,staffed by a pool of scientists and administratorscoordinating national regulatory policy in the envi-ronmental protection field, including participationin international activities (10).

Numerous divisions within the department areconcerned with land use, conservation of wildlifeand habitats, control of toxic substances, air andwater pollution, and wastes. The Toxic SubstancesDivision, for example, is responsible for developingpolicy aimed at protecting human health and theenvironment. Its responsibilities also extend toparticipation in international initiatives. However,the International Division has prime responsibilityfor coordinating United Kingdom policies on envi-ronmental affairs and presenting those policiesbefore the United Nations, the Organization forEconomic Cooperation and Development, the EC,and other bodies (10).

In 1987, a new, centralized agency was formed toenforce environmental laws and regulations inEngland and Wales. Her Majesty’s Inspectorate ofPollution brought together several existing pollutioncontrol agencies: HM Industrial Air Pollution In-spectorate, for controlling major emissions to theatmosphere; HM Radiochemical Inspectorate, forcontrolling all radioactive discharges and disposals;the Hazardous Wastes Inspectorate, for monitoringthe activities of local Waste Disposal Authorities;and the divisions of the Department of the Environ-ment and the Welsh Office responsible for issuingconsents for discharges by the Water Authorities.

Regulatory Issues in Developing Nations

Developing nations, especially those with a largeagricultural economy, depend on pesticides to pro-duce maximum yields. In many of these nations,agriculture is the primary industry and provides thecountry’s primary income. In Ghana, for example,cocoa exports provide a majority of foreign ex-change earnings (8). Misuse and excessive use ofpesticides and chemicals are a significant andwidespread problem in developing countries (15).The WHO has estimated that someone in adeveloping country is poisoned by pesticides


every minute (65). This is due in part to lack of apesticide policy in many developing nations. TheFAO estimated in 1988 that some 50 countriesstill did not have pesticide regulations (20). Thosenations with a policy often do not have the infra-structure or economic resources to implement thepolicy. Moreover, in some developing nations,government officials charged with enforcing pesti-cide policies have a vested financial interest inmaintaining a strong pesticide economy (20). In fact,the governments of many countries are pesticideimporters, manufacturers, and exporters, as well asregulators of pesticides (20). Consequently, regula-tions designed to protect public health and theenvironment may receive little attention. In othercases, pesticides are heavily subsidized, making itcheaper to use pesticides than not (45).

Because of the lack of governmental controls,many developing nations must depend on thepesticide industry to regulate the importation, distri-bution, and use of pesticides, as well as to safeguardpublic health and the environment. In light of this,discussions of regulatory policy often focus on howmuch responsibility pesticide manufacturers and thegovernments of pesticide exporting countries shouldassume. Nations around the world agree that respon-sibility for safety and efficiency in distribution anduse of pesticides must be shared by foreign manufac-turers, exporters, and importers, as well as localformulators, distributors, repackers, advisers, andusers (58). To facilitate the implementation of thisduty, FAO adopted in 1985, and amended in 1987,a code covering such issues as proper pesticidetransport, marketing and advertising, recalls, andnotification on the part of regulators and manufac-turers.

The code calls on industry to adhere voluntarily toits provisions and places an even higher responsibil-ity on industry in countries that lack appropriatepesticide legislation and advisory services (58). Thecode maintains that manufacturers have a duty toretain an active interest in following their prod-ucts to the ultimate consumer. Some assert that theultimate consumer is the local farmer who buys asmall amount of repackaged pesticide product foruse. Following this line of reasoning, the manufac-turer’s duty would end with this purchase. On theother hand, there is the argument that a farmer whoproduces cash crops, as distinguished from a subsis-tence farmer, is not a consumer but a producer (6).These producer-farmers use factors of production—

land, seed, labor, water, fertilizer, pesticides-toproduce a cash crop. The consumerism the person whobuys the produce with the intent of eating it.Accordingly, the pesticide manufacturers have aduty to retain an active interest in following theirproducts—pesticides-to the dinner tables of thefamilies and individuals of the world community(6).One could further argue that U.S. manufacturershave a special duty to protect and ensure the safetyof food treated with U.S.-manufactured pesticidesand eaten by U.S. consumers, regardless of wherethat food is grown.

One controversial provision of the code intendedto address the issues of regulation and education isthat of prior informed consent (PIC). Under PIC, apesticide that has been banned or severely restrictedin one country cannot be exported to another countryunless the importing country’s government has beenfully informed of the reasons for the regulatoryaction and has consented to the importation of thepesticide (58). Pesticide exporting countries gener-ally do not favor PIC and assert that it is tootime-consuming, expensive, and burdensome forindustry (20). Representatives of importing coun-tries, on the other hand, claim that, in the absence ofregulatory controls, PIC is the only avenue forallowing governments to determine if pesticidesbanned in other countries should be permitted withintheir borders. Although PIC is still a voluntarypractice, the Netherlands became the first coun-try to incorporate it into legislation and seek tomake it legally binding (20).

The WHO has classified pesticides on the basis ofthe hazards they pose. Hazard is defined as thelikelihood that a pesticide will cause immediate orshort-term adverse effects or injury under circum-stances of ordinary use. These classifications arebased on the oral and dermal toxicity of thepesticide’s active ingredient. Countries adopting theFAO code are also supposed to adhere to thefollowing WHO toxicity classification in labelingtheir pesticides:

. IA Extremely Hazardous,

. IB Highly Hazardous,

. 11 Moderately Hazardous, and

. III Slightly Hazardous.

In addition, the Pesticide Action Network (PAN)has initiated a Dirty Dozen Campaign on aninternational scale to publicize the 12 most hazard-ous pesticides used worldwide, most of which are


neurotoxic. Since the campaign began, some coun-tries have banned certain pesticides on the DirtyDozen list, and others have restricted the availabilityof them (20). The pesticides are:

●

●

●

●

●

●

●

●

●

●

●

●

camphechlor (toxaphene),chlordane/heptachlor,chlordimeform (Galecron),dibromochloropropane (DBCP),DDT,aldrin/dieldrin/endrin,ethlene dibromide (EDB),lindane/hexachlorocyclohexane (HCH),paraquat,ethyl parathion,pentachlorophenol (PCP), and2,4,5-T.

Pesticide workers in developing countries arefrequently not provided with appropriate protectiveclothing and equipment to guard against oral anddermal exposure when applying pesticide products(30). In tropical or semitropical climates, the temper-ature is often too hot to permit workers to comforta-bly wear protective clothing designed for use inmore temperate climates (protective clothing isoften made of plastic, rubber, or other nonporousmaterial). Despite workers’ lack of protective cloth-ing, pesticides are sometimes sprayed from aircraftwhile workers are in the fields. Pesticides may alsobe sprayed from canisters strapped to the backs ofunprotected workers.

Besides allowing the export of pesticides thathave been banned or severely restricted for use inthis country, present EPA regulations allow theexport of pesticides that have never been reviewedby the Agency. Some critics argue that if a pesticideis not safe enough for use in the United States, itshould not be exported. The FAO code holds that thefact that a product is not used or registered in theexporting country is not necessarily a valid reasonfor prohibiting export of that pesticide (58). Mostdeveloping countries are located in tropical andsemitropical regions. Their climatic, ecological,agronomic, and environmental conditions, as well astheir social and economic needs, may be differentfrom those of industrialized nations. Accordingly,their pest problems may be quite different. Thegovernment of the exporting country, therefore, maynot be in the best position to judge the suitability,efficacy, safety, or fate of the pesticide under

conditions in the country where it may ultimately beused.

Critics of this export policy argue, however, thatforeign relations problems could arise if productsconsidered too unsafe and hazardous for use bypeople in the United States are deemed safe for useby people abroad. Although people in developingcountries use only 10 to 25 percent of the world%pesticides (7,21), it is estimated that they accountfor as much as 50 percent of the acute poisoningsof pesticide applicators and between 73 and 99percent of their deaths (15). Furthermore, residentsof the exporting nation are exposed to potentiallydangerous chemicals during domestic productionand eventual consumption of imported foods treatedwith the pesticides.

Following is a summary of regulatory activities incertain developing countries where pesticides areused. Boxes 9-A and 9-B illustrate problems thathave occurred in developing nations. Although eachof the profiled countries has some regulatory struc-ture in place, each also has many problems with theimport, distribution, and use of pesticides, resultingin health problems of varying degrees for farmwork-ers and consumers. In selecting the countries for thissection, an attempt was made to obtain a geographicspread.

Malaysia

The Pesticides Board under the Malaysian De-partment of Agriculture has regulatory authority forpesticides in Malaysia. The Pesticides Act, thePesticide Registration Rules of 1976, the PesticideRules on Importation for Educational or ResearchPurposes of 1981, and the Food Act of 1983 set outthe language governing pesticide use (39).

Malaysia follows FAO guidelines with respect todata requirements for pesticide registration. How-ever, all data, including efficacy data, may be fromforeign sources. Data are evaluated and a recommen-dation is submitted to the Pesticides Board, whichhas authority to grant registration (39). Accordingly,a pesticide may be reviewed and approved for use inMalaysia with the approving authority dependingentirely on data from the country of export.

The Department of Customs controls the importof all pesticides except those imported for researchpurposes, which are controlled by the MalaysianDepartment of Agriculture. The Department ofAgriculture also controls the production, sale, and

Chapter %-international Regulatory and Research Activities . 251

Box 9-A—Problems With Neurotoxic Pesticides in Developing Countries

Irregularities concerning labeling, packaging, storage,sale, import, and advertising of pesticides have causedillness, injury, and death in many developing countries, asthe following examples illustrate:

Pesticides are commonly repackaged without labelsin Senegal, but labels are of little use anyway,because most pesticide users are illiterate. Instruc-tions such as “in case of intoxication, call a doctor”are meaningless in rural areas where there are nodoctors for miles, no telephones, and only sporadictransport.

. In Indonesia, an outbreak of mosquito-spread denguefever caused several deaths. The Ministry of Healthsent an officer to spray the area with malathion, aclass HI, slightly hazardous pesticide. The officer wasphotographed spraying malathion while children

Photo credit: Widjanarka

were running behind him to play in the pesticide mist (see photograph above).● In Papua, New Guinea, very few companies provide labels in Tok-Pisin, the widely spoken local language.

Some pesticide products had labels in French. One pesticide, selecron, was found in stores with no label atall.

● Many of the pesticides in Thailand, Indonesia, and the Philippines do not have child-proof packaging. Someliquid pesticides have easily opened screw caps, and powdered pesticides can be bought in plastic bags thatan older child can open.

. In Indonesia, some pesticides were repackaged into clear plastic bags without labels. Workers wore no masksor gloves. Unlabeled bags of temik, which is 10 percent aldicarb, a class IA, extremely hazardous neurotoxicpesticide, were available in stores. Aldicarb is more acutely toxic to mammals than any other pesticidepresently in use.

. In the Sudan, a family of eight died in 1985 from eating pesticide-poisoned bread made from pretreatedwheat meant for seed. The pretreated wheat had been in badly labeled sacks stacked next to consumablewheat in an agricultural store.

In Brazil, a 1987 advertisement described deltamethrin as “the safest insecticide in the world.”Deltamethrin is classified as class II—moderately hazardous by the International Code of Conduct on theDistribution and Use of Pesticides of the Food and Agriculture Organization of the United Nations.

● In Senegal, used pesticide containers are often recycle-d to carry food, milk, or cooking oil. In one village,19 people from two families died as a result. The cook used oil sold in a bottle that had previously containedethyl parathion, a class Ia, extremely hazardous pesticide.

. In Brazil, when a number of states passed laws banning imports of pesticides banned in their countries oforigin, translational pesticide corporations and importers filed legal action and succeeded in getting the lawsdeclared unconstitutional.

SOURCE: G. Goldenman and S. Rengam, Problem Pesticides, Pesticide Problems (Penang, Malaysia: International Organization of ConsumersUnions and Pesticide Action Network, 1988).

use of pesticides and checks for compliance with killed by exposure to just that one pesticide (48).regulatory policies. The Pesticides Board regulatesadvertisements of pesticides (39).

Residues on vegetables are monitored under theFood Act of 1983. To date, there is no system formonitoring pesticide poisoning except for occa-sional reports from hospitals. Following the deathsof two teenage girls from field exposure to paraquatin 1985, it was revealed that 1,200 workers had been

Both government and the private sector have imple-mented training programs on the safe handling ofpesticides. These programs are geared toward farm-ers, applicators, dealers, distributors, manufacturers,and medical personnel (39).

Residues on vegetables are monitored under theFood Act of 1983, which prescribes maximumresidue limits (5). In reality, monitoring and testing


Box 9-B—Incident at Lake Volta, GhanaIn Achedemade Bator, a fishing village on Lake Volta, a serious poisoning incident resulted from improper

use of Gammalin 20, the trade name for lindane, a potent neurotoxic substance. The villagers, almost all of themilliterate, derived their income through fishing on the lake. The village fishermen discovered that by pouring lindaneinto the lake, fish would float to the surface and could be easily caught. This proved to be a very quick and efficientway of hauling in a catch. Any fish not consumed were salted, smoked, or sold.

Exposure to lindane may cause dizziness, headaches, convulsions, muscle spasms, brain disturbances, andunconsciousness. Some villagers experienced symptoms of lindane poisoning from consuming poisoned fish andusing the lake as a source of drinking water but never associated their health problems with use of the chemical.Fishermen knew something was wrong when the fish population in the lake rapidly declined, and housewives couldeasily identify Lake Volta fish by their smell, but villagers continued to eat the deadly fish. When a connection wasmade between the illnesses and fish consumption, villagers cut off the heads of the fish and continued to eat thebodies, believing that decapitation would rid the fish of all poison.

Other plants and animals in the lake were killed as well. It was not until the intervention of the Associationof People for Practical Life Education, a Ghanian organization, and the blessing of the village witch doctor that thevillagers stopped using lindane for fishing and returned to nets and traps. In villages throughout Africa, fishing withpesticides continues where people have not been educated about the safe and effective use of these toxic substances.

SOURCE: R. Norris (cd.), Pills, Pesticides & Profits (Croton-on-Hudson, NY: North River Press, 1982).

are minimal (5). Concern about pesticide residues in Philippine Institute for Pure and Applied Chemistry,food has resulted in the formation of the ConsumersAssociation of Penang (CAP), the largest and mostvocal citizens’ organization in the developing worldfocusing specifically on consumer rights (70). CAPhas discovered organochlorine pesticides (DDT,aldrin, BHC, dieldrin, chlordane), many of which arebanned in the United States, in Malaysia’s rainwater,soil, drinking water, and food crops. CAP monitorspesticide poisoning of workers and residues in foodand has pressured the Malaysian government totighten its regulations on pesticides (70). In a recentstudy conducted by the Malaysian Department ofAgriculture, it was discovered that 54 percent ofthe 1,214 agricultural workers studied had expe-rienced some form of pesticide poisoning (22,44).

Philippines

In the Philippines the private sector controls thepesticide industry, which is dominated by localorganizations representing the major multinationalcompanies (5). Virtually all of the pesticide businessis transacted by some 20 companies in the tradeassociation-the Agricultural Pesticide Institute ofthe Philippines (5).

There are several laws affecting the pesticideindustry. A presidential decree enacted in 1977regulates pesticides. Quality control of pesticides isdone by the Fertilizer and Pesticide Authority (FPA)through the Bureau of Plant Industry (BPI) and the

on the basis of complaints from users (39). Qualitycontrol during production and for imports is done byprivate companies. Pesticide dealers and ports ofentry in the 72 provinces and 12 regions areinspected, but critics argue that this system needsimprovement and strengthening (39). An FPA per-mit is required for all imports of pesticides, regard-less of quantity. The FPA controls production, sale,and use of pesticides through a licensing scheme,and in collaboration with the Philippine Board ofAdvertisers controls advertisements of pesticides(39).

There is no system in operation to monitorpesticide poisoning cases in humans except foroccasional reports from hospitals and doctorstrained under the FPA Agro-Medical Program.Pesticide dealers must be trained in the safe handlingof pesticides before they can obtain a retail license.Commercial pest control companies must obtaincertification for all of their operators (39). Market-basket samples of vegetables are routinely analyzedfor residues, particularly for organochlorines andorganophosphates, by the BPI (5). Other agenciesmonitor residues in lakes, rivers, and streams, whileexporters of agricultural products analyze shipmentsprior to export (5).

The Philippines is the home of the InternationalRice Research Institute, which helped create thegreen revolution of the 1970s. This revolution saw


the production of new hybrid seeds, developed toproduce higher yields with the correct amount offertilizer and water (70). These laboratory-bredseeds were more susceptible to pests and requiredincreased use of pesticides. Although the new seedshave increased production, the Philippines remainsone of the hungriest nations in Asia, according to theAsian Development Bank and WHO (70).

Some. years ago, the Farmer’s Assistance Boardwas formed by peasants and students to studypesticides. The board blames the large volume ofpesticide use in the Philippines on the big exporters,as well as on the International Rice ResearchInstitute. The board points to the demand for highestyield and blemish-free products as the reasons forthe country’s continued dependence on large quanti-ties of pesticides.

India

The Insecticides Act (1968) and the InsecticidesRules (1971) govern pesticides in India. The Actregulates manufacture, formulation, distribution,and sale of pesticides through a licensing system.Five agencies have been created to implement theselaws. Locally generated toxicity and residue data forformulations are required in most instances; how-ever, complete efficacy data are required only forregistration of a new pesticide. The Pesticide Regis-tration Committee and the Central InsecticidesBoard review data for registration, referring topublications and decisions by FAO, WHO, andEPA, among other organizations. India does notadhere to FAO guidelines with respect to labeling. Itdoes follow the FAO color coding of labels based ontoxicity, but the warning symbols differ from thosesuggested by FAO. Pesticides are classified intovarious categories of toxicity, but the limits set differfrom those recommended by WHO (39). To date,119 active ingredients and their formulations havebeen registered.

The improper use of pesticides is a major problemin India (5). Few farmers are aware of the potentialhazards associated with the use of pesticides (5).Crops are often sprayed with insecticide immedi-ately before and after harvest because of a belief thatpre- and postharvest spraying will increase freshnessand preservation (5).

India “phase registers” new pesticides. Firstthere is a trials clearance, then a provisional registra-tion, which is valid for 2 years and subject to certain

conditions, and finally a full registration. There isalso “me-too” registration, which allows a secondregistrant to obtain registration for a pesticidesubject to proof that the product is identical to theone already registered. There is usually a letter ofagreement between parties on use of data (39).

The Insecticides Act mandates that pesticidequality be checked by the Central Insecticide Labo-ratory. Rigid controls are set for preregistrationpurposes, but once a product is on the market,quality control is not pursued (39). Quality controlof products during production is monitored not bythe government, but by private companies. Compli-ance with regulatory policies is enforced by stategovernments, and imports are allowed only throughcertain ports of entry (39). No pesticide may beimported without a registration certificate. It isinteresting to note that many pesticides which havebeen banned or severely restricted in the UnitedStates are produced in India (70). Several foreignmanufacturers have plants in India (70).

Increased agricultural output does not necessarilymean increased food consumption for local residentsif the residents are too poor to afford food. Despitethe fact that there were vast increases in wheat yieldsin the Punjab district in the 1960s, the portion of therural population living below the poverty lineincreased from 18 to 23 percent (28). While true thatpesticide use may increase crop yield and bolster theeconomy of a developing country, in this particularinstance the economic prosperity of the local inhabi-tants declined.

The Central Food Laboratories monitor pesticideresidues and adulterants in food, but this systemneeds strengthening. State governments are requiredto obtain reports from their officers on pesticidepoisonings, but this is not a thorough monitoringsystem. Both state and central governments and thepesticide industry have implemented training pro-grams for safe use and application of pesticides (39).

Costa Rica

The Law for the Control of Pesticides (1979) andthe Law Governing Occupational Health (1981)regulate pesticides in Costa Rica. Along with otherCentral American countries, Costa Rica has adoptedthe provisions of the Basic Document on Regulationof Registration, Marketing and Control of Agricul-tural Chemicals for Countries of Central America,prepared under the auspices of the Inter-American


Institute for Cooperation on Agriculture in 1985. APesticide Commission has also been formed to carryout the pesticide registration program (39).

Registration requirements are generally in accor-dance with FAO guidelines. Local efficacy data fornew products are to be generated either directly bygovernment research organizations or by privatecompanies under government supervision. Efficacydata from other Latin American countries areacceptable for products already registered. EPAtolerances must also be submitted, along with acertificate of registration and a certificate of analysisfrom the country of origin and evidence of registra-tion from other countries. Labeling is evaluatedaccording to guidelines agreed on under the BasicDocument. Full registration is valid for 3 to 5 years,experimental permits are issued, and me-too regis-tration is allowed. As with Mexico and Ecuador, allchlorinated compounds that accumulate in the foodchain are banned, but the government reserves theright to use them in cases of emergency wheneconomical substitutes are not available (39).

Costa Rica has one of the strongest enforcementsystems in Central America. Import permits are

necessary, and there is a licensing scheme forformulation, distribution, and sale of pesticides. TheMinistry of Health has done some monitoring offood residues and keeps a record of poisoning cases.The government and private sector carry out trainingprograms for pesticide workers, and the governmenthas published a training manual for physicians.

Mexico

In Mexico, the principal pesticide legislation isthe Law on Plant and Animal Protection, which wasadopted in 1940. The law was amended in 1974, andrules were added in 1980 to implement it. FAOguidelines are generally followed, with local effi-cacy data generated either directly by governmentresearch organizations or by private companiesunder government supervision (39). All test proto-cols must be approved by the government. Emphasisis on evaluation of efficacy data, while toxicologicaland residue data are reviewed by experts. Labelevaluation follows the Basic Document guidelinesagreed on by Latin American countries, and theWHO classification system for pesticides has beenadopted, with certain modifications (39). Full regis-tration is valid for 3 to 5 years, with permits issued

Photo credit: Kay Treakle, Greenpeace

Unprotected workers spray paraquat on coffee plants, Chiapas, Mexico

Chapter International Regulatory and Research Activities . 255

for experimental purposes. Me-too registration isallowed with the same data and information require-ments as for all registered products.

All chlorinated compounds that accumulate in thefood chain are banned, but the government reservesthe right to use them in cases of emergency wheneconomical substitutes are not available (39). Asrecently as 1987, some 28 pesticides that werebanned or severely restricted in the United Stateswere being used in Mexico (18). Endrin, which wasseverely restricted in the United States in 1979, wasgiven a renewal registration for 2 years in 1984 (18).Mexico imports a large percentage of pesticides, butthere are also some 300 formulation plants in thecountry (18). In 1987, domestic production ofpesticides was estimated at 32,000 tons per year(18).

The government and private industry share re-sponsibility for quality control, but compliance withregulatory policies is usually enforced only aftercomplaints from the field. Training programs forfarmers, distributors, and physicians are sponsoredby government and private industry, but monitoringof pesticide poisonings is sporadic. Imports arecontrolled through the issuance of import permits,and formulation, distribution, and sale of pesticidesis controlled through a licensing scheme (39).Residues in export crops are monitored regularly,following regulations imposed by the importingcountry (39).

Ecuador

In addition to enacting its own legislation in 1984,Ecuador has consented to implement guidelinesdealing with registration data and labeling agreed onby Latin American countries in the Andean region.FAO guidelines form the basis for data require-ments. Either government research organizations orprivate companies under government supervisionmust generate local efficacy data. Further, proof ofregistration in the country of origin and registrationin other countries is required (39).

There is little evaluation of data except forefficacy. Labeling is strictly evaluated, based on theguidelines agreed on by the Latin American coun-tries. Other organizations are looked to for guidance,among them FAO, WHO, EPA, the National Agri-cultural Chemicals Association, and the Interna-tional Group of National Associations of Manufac-turers of Agrochemical Products.

Photo credit: Amerkan Cyanamid

Worker spraying banana plants in Ecuador

All chlorinated compounds that accumulate in thefood chain are officially banned, but the governmentreserves the right to use them in cases of emergencywhen economical substitutes are not available (39).Parathion and toxaphene are two pesticides bannedin Ecuador, while DDT and methyl bromide areamong those restricted to specified uses. U.S. EPAregulations regarding banning and restrictions aresupposed to be closely followed (39), yet DDT,which has been banned by EPA for use in the UnitedStates, can be used in certain circumstances inEcuador.

Both government and private industry have qual-ity control programs. The Fundacion Natura (NatureFoundation), an environmental group, monitorscompliance with regulatory policies and reportsviolations to the government. Government inspec-tors are also assigned to monitor compliance. TheDepartment of Commerce and the Ministry ofAgriculture issue import permits, and there is alicensing scheme for formulation, distribution, andsale of pesticides.

Prior government approval is needed for anypesticide advertising, but there has been minimal


monitoring of residue on food and crops. A record ofany poisoning cases reported by hospitals is main-tained by the Ministry of Health. Government andthe private sector, as well as industry, have trainingprograms for extension workers, farmers, distribu-tors, doctors, and technical and sales representatives.

Kenya

In Kenya, the Pesticide Control Board Act wasimplemented in 1982, with regulatory authorityvested in the Pesticide Control Product Board. TheSpecialist Approval Committee for AgriculturalPesticides evaluates data generally, in accordancewith FAO guidelines. At present, there is noinformation available concerning labeling require-ments, no national residue tolerances, and no systemof pesticide classification, although WHO classifi-cation is being reviewed for possible adoption. Onlyregistered products can be imported and used, butthere are no restrictions regarding the availability ofthese products (39).

For the most part, quality control is left toindustry. Residue monitoring is not usually done,and there is no system in operation for monitoringpesticide poisoning cases (39).

INTERNATIONALNEUROTOXICOLOGICAL

RESEARCHActive interest in neurotoxicity began in the

United Kingdom during and after World War II.Since that time, research efforts in the United Stateshave gradually increased. The United States is nowthe world leader in environmental legislation and ingovernment funding of neurotoxicology research.Research in other countries has been narrower andmore specific. The Scandinavian countries havebeen active in research on the neurotoxicity oforganic solvents (73), and other European countrieshave supported research on compounds of particularconcern in occupational settings, such as pesticidesand heavy metals (16,36). In most cases, however,no systematic national effort has been undertakensimilar to that in the United States (2).

Several international conferences have taken placeduring the past 10 years on the subject of neurotoxi-cology, some of which were sponsored by EPA andthe National Institutes of Health. Two internationaljournals published in the United States, Neurotoxi-cology and Teratology and Neurotoxicology, were

Photo credit: Monsanto Agricultural Co.

Surveying the harvest, Kenya

established in 1979, and the Society of Toxicologyin the United States has a sizable subsection devotedto neurotoxicology. Outside the United States,sufficient interest has been generated in neurotoxi-cological issues that a new society, the InternationalNeurotoxicology Association, has been formed.This society held its first meeting in 1987, withattendance by approximately 200 scientists fromEurope and the United States. The first comprehen-sive text on neurotoxicology was published in 1980(52).

Major Directions of Academic, Industrial, andGovernment Research

In the past, research efforts were often initiatedfollowing industrial exposures that caused severehuman intoxications. For example, with the adventof the vulcanization of rubber, carbon disulfidepoisoning in workers in the rubber industry becamecommon in many European countries (71). With theintroduction of rayon, the manufacture of which alsorequired the use of carbon disulfide, poisonings dueto use of this solvent became a worldwide problem(68). Improvements in occupational hygiene havelargely eliminated cases of severe poisoning; never-theless, what has emerged instead is the problem ofchronic low-level exposures to this and other com-pounds. The development of human testing proce-dures to measure more subtle symptoms has beenlargely accomplished in Finland (49).

The toxicity of lead has been known sinceantiquity (51 ). Nonetheless, large-scale lead poison-ing continues to be an international public healthproblem because of lead water pipes, the use of

Chapter 9-International Regulatory and Research Activities . 257

Illustrated by: Ray Driver

lead-based paints, and the addition of lead togasoline. Much of the basic research involvinganimal models of lead toxicity was done in theUnited States (67). Using the diagnostic proceduresdeveloped for the detection of exposure to organicsolvents, Finnish researchers have demonstratednervous system damage in low-level occupationalexposures of adults to lead (49). Research into leadtoxicity is still supported enthusiastically in manycountries because of accumulating evidence thateven exposure levels previously considered harm-less (particularly in children) have been shown tohave adverse effects on health (ch. 9). This has ledthe WHO European Office to sponsor a multina-tional study of the effects of childhood lead intoxica-

tion. As of 1989, lead additives have been restrictedin the United States and in some parts of Europe.Thus, worldwide interest in lead toxicity continues,although outside the United States research is notsupported in a programmatic way by individualgovernments. It appears that this role has been takenover by international bodies such as WHO.

Another major environmental contaminant ismercury. Exposures to mercury in industrial settingshave been well described since the 19th century (34).Mercury became a public health problem because ofthe widespread use of organic mercury compoundsin agriculture as fungicides. The first major outbreakof methyl mercury poisoning occurred in Japan in1953 and was followed by outbreaks in many otherparts of the world, notably Iraq (see ch. 2). Japanesescientists have actively pursued research on themechanism of neurotoxicity of organic mercurycompounds (55). This was followed by a largeScandinavian (mostly Swedish) research effort be-cause of contamination of lakes by mercury runoff(19). U.S. investigators have been involved inmercury research since the Iraq episode, in 1971 to1972, and have examined such problems as theteratogenic effects of methyl mercury on the behav-ior of animals (17). Other metals that have beenstudied internationally include manganese, cad-mium, and the organotins.

Interest in the neurotoxicity of organic solventshas increased in recent years. Pioneering work inScandinavia was followed by mechanistic studies inthe United States (47) that revealed the relationshipbetween human symptoms and underlying biologi-cal alterations. Scandinavian workers have been thefocus of a number of occupational hazard studies. Arecent monograph entitled Organic Solvents and theCentral Nervous System was published jointly byWHO and the Nordic Council of Ministers (73). Thisdocument addresses the problems of occupationalexposures, the illness caused by these exposures,and the diagnostic procedures for identifying theillness. In 1988, the WHO-Nordic Council ofMinisters met to design the “definitive” study ofchronic effects of exposure to solvents on thenervous system of workers (75).

The widespread use of highly toxic pesticides hasled to intense worldwide research on the neurotoxic-ity of these compounds. In fact, the beginning of theenvironmental movement has been attributed to thepublication of Rachel Carson’s book Silent Spring,


which dealt with the ecological effects of indiscrim-inate pesticide application. The continuing develop-ment of new pesticides has caused the research effortto be sustained, not only to protect human popula-tions, but also to safeguard nontarget populationsfrom inadvertent exposure to these compounds.

One way to document international researchtrends is to summarize the distribution of researchpapers published by non-U.S. authors in the twointernational journals devoted to neurotoxicology.Table 9-1 indicates the various neurotoxic sub-stances investigated in papers published in twojournals between 1979 and 1987.

Heavy metals as a group clearly represent themajor area of interest. They are followed by organicsolvents, pharmaceutical agents, and pesticides.Since the two neurotoxicology journals are rela-tively new, one can assume that a large proportion ofneurotoxicological research has also been publishedin other journals. In addition, each of the non-English-speaking countries listed has journals in its ownlanguage, and researchers also publish in thosejournals. This is particularly true of scientists in theSoviet Union, who publish only infrequently inEnglish-language journals. Thus, while this surveyof published research outside the United States maynot be truly representative of international neurotox-icological research, it is probably a reasonableindicator of general trends in international research.

To gain another view of current research trends, itis useful to examine projects presented at the firstmeeting of the International Neurotoxicology Asso-ciation in the Netherlands, May 10-16, 1987. Themeeting was attended by 135 scientists from 21countries. The largest contingent came from theUnited States (23), followed by the Netherlands(20), West Germany (15), England (1 1), Italy (1 1),and all other countries (fewer than 10 each). Anexamination of their places of employment indicatesthat 37 percent of the attendees were from govern-ment laboratories, 37 percent from academia, 23percent from industry, and the remainder from avariety of institutions. Of the U.S. participants, 22percent were from government laboratories, 65percent from academia, and 9 percent from industry.An examination of the topics presented indicatesthat the trends outlined above have not changedmarkedly (table 9-2). Following tradition, 50 percentof the papers dealing with solvent toxicities camefrom Scandinavian countries.

Table 9-1-Neurotoxic Substances Investigated inPapers Published in Two International Journals,

by Country, 1979-87

Country Substances investigated (No. of papers)Canada

England

Italy

India

Japan

FranceMexicoFinland

Ethanol (3); manganese (2); cadmium (2); lead (2);pharmaceutical agents (2); acrylamide (1 ); zinc (1 );aluminum (1); herbicides (1); hydrogen peroxide (1);chlorinated hydrocarbons (1)Pyrethrins (7); pharmaceutical agents (7); or-ganophosphates (2); solvents (l); acrylamide (l);mercury (1); herbicides (1)Pharmaceutical agents (8); organophosphates (2);mercury (1); solvents (1); bismuth (1); caffeine (1)Manganese (4); organophosphates (l); lead (l);cadmium (1); solvents (l); sulfur dioxide (1); zinc(1); styrene (l); herbicides(1)Mercury (5); solvents (3); cadmium (l); pyrethron(1); pharmaceutical agents (1)Mercury (3); solvents (1); tellurium (l); lead (1)Solvents (6)Lead (4): solvents (4): ethanol (1)

SOURCE: Office of Technology Assessment, 1990.

Table 9-2-Subjects of Neurotoxicological ResearchPresented at a Major International Conference

Chemical Papers (No.)Insecticides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25Solvents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23Lead . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8PCBs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2Acrylamine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2Methyl mercury . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1Styrene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1Carbon monoxide . . . . . . . . . . . . . . . . . . . . . . . . . . . 1Nitrous oxide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1Pharmaceutical agents . . . . . . . . . . . . . . . . . . . . . . 4Experimental compounds . . . . . . . . . . . . . . . . . . . . 6SOURCE: Office of Technology Assessment, 1990.

One meeting may not represent a typical sampleof international research in neurotoxicology, but itprovides a useful example of current neurotoxicol-ogical research in the Western industrialized world.No researchers from the Soviet Union attended thismeeting; however, two individuals from EasternEurope, one each from Hungary and Czechoslova-kia, attended. The number of neurotoxicologists inboth of these countries is very small, as determinedby publications in the literature. For much of the restof the world, neurotoxicology as a discipline doesnot exist. There are some exceptions, however. Forexample, there are active researchers in Japan, India,China, and Argentina, with well-identified centersfor such research. Indian researchers have tradition-ally published in English, and this practice isbecoming increasingly common among Chineseresearchers as well. In addition, experimental re-


search on the neurotoxicity of the grass pea is nowunder way in Ethiopia.

Neuroepidemiology

International activities in neuroepidemiology havetaken place on all six inhabited continents. Neuroep-idemiologists in England are currently studying riskfactors for stroke and are investigating the epidemi-ology of multiple sclerosis. In Japan, epidemiologi-cal inquires into the etiology of neurodegenerativedisorders (including amyotrophic lateral sclerosis,Parkinson’s disease, Alzheimer’s disease) have beenundertaken. One country with a major effort inneuroepidemiology is Italy. Italian efforts in thisarea may be traced back to a series of courses onneuroepidemiology taught in 1979 by a group ofU.S. and Italian epidemiologists. The fruits of theseefforts have included major work in the epidemiol-ogy of dementia. More recently, WHO has begun aninternational initiative in the epidemiology of de-mentia. It is not clear, however, whether this workwill be extended to other neurodegenerative condi-tions. It is possible that some of these efforts will befocused on geographic isolates of neurologicalconditions, for example, the Faroe Islands andmultiple sclerosis, Guam and dementia, and Guamand amyotrophic lateral sclerosis. An internationalcollaboration to investigate the latter two phenom-ena is now forming and will likely begin its activitieswithin the next year (31 ).

International Cooperation

Neurotoxicological research has been primarilyan intranational effort. In recent years, some interna-tional cooperation has been initiated by WHO andthe U.S. National Toxicology Program, but thus farthis has occurred only in specific areas, such as leadtoxicity, solvent toxicity, and the development oftesting methodologies (74). The limited scope ofinternational cooperation is large] y due to the lack offunds available for such efforts.

Comparison of U.S. and ForeignResearch Programs

The neurotoxicity research effort in the UnitedStates is larger in depth and scope than that in othernations. Both leading books in this area were writtenby American authors and editors (4,52). Bothinternational journals in the field are published in theUnited States, and a review of the publishedliterature in neurotoxicology reveals that about 90

percent originates in the United States. The qualityof the work is generally considered to be excellent.As mentioned previously, other countries haveexcelled in some areas of research; this is particu-larly true with respect to the solvents researchconducted in Scandinavia. American research on themechanisms of toxicity of solvents is generallyconsidered to be outstanding.

Resources

The United States has a limited number ofdoctoral-level training programs in neurotoxicol-ogy. Because of its unique educational system, morescientific manpower is available in the United Statesthan in other countries. In most European countries,the standard educational program in the life sciencesis the medical degree, or the equivalent of the M.D.Consequently, almost all researchers in Italy, Scan-dinavia, and Germany are trained first as physiciansand then as researchers. These individuals mayeventually obtain a doctorate if they choose aresearch career. In countries such as Italy, whereresearch positions are very difficult to obtain, mostphysicians choose nonresearch careers rather thanrisk being unemployed. Although employment op-portunities are somewhat better in Scandinavia thanin Italy, it is still difficult to establish a researchcareer because of the scarcity of positions.

The success of the American research enterpriseis due not only to the relative availability of funding,but also to the manner in which the funds areadministered. Despite some inherent flaws, the peerreview system in the United States generally ensuresthat the best scientists in a given field obtainfunding. In many other parts of the world, researchis often supported by a system in which fundingdecisions are made solely by the director of aninstitute or the chairman of a department, withoutpeer review of the proposed research.

Future Directions

A recent review (1) listed 850 chemicals in theworkplace that may be neurotoxic. Apart from thesubstances listed in tables 9-1 and 9-2, most of thesechemicals have not been studied. The internationalchemical industry produces several thousand newchemicals every year, most of which are not testedfor neurotoxicity. Japan and France now requireneurotoxicity testing for new chemicals (53), butthese tests are elementary in nature and are likely tomiss more subtle and insidious toxic effects.


Photo credit: Jerry Deli

At present, the major classes of neurotoxicsubstances-heavy metals, solvents, and pesticides—have been identified. However, despite major re-search efforts, there is still no clear understanding ofthe mechanisms of toxicity of most of these chemi-cals. In order to protect human populations fromchronic low-level intoxication, it is essential tounderstand the properties and potential health ef-fects of new and existing chemicals. Because of theenormity of the testing task, a coordinated interna-tional approach would be highly beneficial.

Foreign Governments Likely To TakeLeadership Roles

In some European countries, notably West Ger-many and Sweden, environmental movements arebecoming increasingly influential. It is likely thatthese nations will play leading roles in supportingresearch and in developing regulations to controltoxic substances. The Federal Republic of Germanyhas already acted to remove lead from gasoline andto fund studies of lead toxicity in children. As

outlined above, all of the Scandinavian countries(Sweden, Denmark, Norway, and Finland) havetraditionally supported research on solvents. Thesepatterns are likely to continue and may broaden tothe investigation of other agents as environmentalmovements grow. Political events in the SovietUnion have led to the emergence of an environ-mental movement, and it appears that the Sovietgovernment will also take a more active role in theseissues. In the Far East, both the People’s Republic ofChina and Japan are faced with major pollutionproblems and are becoming increasingly involved intoxicological issues.

SUMMARY AND CONCLUSIONS

Like most environmental concerns, neurotoxicityis a problem not limited by national boundaries.Pollutants can readily cross national borders, haz-ardous chemicals are frequently imported and ex-ported among both industrialized and developingnations, and adulterated food and commercial prod-ucts enter the United States despite current regula-tory efforts. Strategies to limit human exposure toneurotoxic substances should be devised in thecontext of both national and international regulatoryand research initiatives.

Despite numerous regulations governing the ex-port and import of neurotoxic chemicals and prod-ucts containing them, most countries do not ade-quately protect human health and the environmentfrom these substances. Most industrialized nationshave policies and procedures in place to regulate theimport, distribution, and use of toxic chemicals,implicitly including neurotoxic substances. Somedeveloping nations have limited regulations toprotect workers and consumers from the adverseeffects of neurotoxic substances. Developing na-tions that do have regulations often do not have theresources to enforce them. Developing countries useonly 10 to 25 percent of the world’s pesticides, butthey account for as much as 50 percent of the acutepoisonings of pesticide applicators and between 73and 99 percent of their deaths. This lack of effectiveregulation and enforcement in developing nationshas a negative impact not only on public health andenvironment in the user country, but also in industri-alized nations, including the United States, wherepeople process and consume pesticide-treated cropsimported from developing nations.

Chapter 9-Internatioral Regulatory and Research Activities ● 261

Both TSCA and FIFRA contain provisions ex-empting certain products produced for export fromthe requirements that apply to products sold for usein the United States. In most instances, TSCArequirements do not apply to substances manufac-tured, processed, or distributed for export. Therequirements do, however, apply if it is determinedthat the substance will present an unreasonable riskof injury to public health or the environment withinthe United States. In addition, because pesticidesintended solely for export are exempt from thepublic health protection provisions of FIFRA, pesti-cide manufacturers can legally export banned, se-verely restricted, or never registered substances thathave been deemed too hazardous for use in thiscountry. Companies that do so are required to notifythe importing country that the exported pesticideshave been banned, severely restricted, or neverregistered for use in the United States. Some suchpesticides are used on food crops that are importedback into the United States for consumption. Criticsof this practice have termed it the ‘circle of poison.

On January 15, 1981, several days before the endof his term, President Jimmy Carter issued anExecutive Order which put controls on exports ofsubstances that were banned or severely restricted inthe United States. Several days after Ronald Reaganbecame President, he revoked the order.

While pesticides may be needed to obtain suffi-cient food to feed the ever-increasing world popula-tion, many observers argue that ample food suppliesare currently available and that better distribution ofexisting food stores is necessary. Responsible con-duct on the part of persons who manufacture,distribute, and use pesticides is mandatory if irre-versible harm to world public health and the worldenvironment is to be minimized. Education andliteracy levels of persons handling pesticides mustbe considered and appropriate information tailoredto their needs. Regulations currently in place must beadhered to and new legislation enacted when theneed arises. Alternative methods of pest controlshould be investigated and developed. Cooperativeefforts on the part of governments in industrializedand developing countries, industry, environmentalgroups, and other international organizations arenecessary to ensure the safety of the world commu-nity.

Active interest in neurotoxicity began in Englandduring and following World War H. Since that time,

efforts in the United States have gradually increased.Today, the United States is the world leader inenvironmental legislation and government fundingof neurotoxicological research. The Scandinaviancountries have been active in research on theneurotoxicity of organic solvents. Other Europeancountries have supported research on compounds ofparticular concern in occupational settings, such aspesticides and heavy metals.

International research activities tend to focus onthe heavy metals (lead and mercury), organicsolvents, and pharmaceutical agents. Foreign neuro-toxicology-related scientific papers published ininternational journals most often originate fromauthors in Canada, England, Italy, Australia, andJapan. A number of papers originate from authors inFrance, India, Sweden, Finland, and Mexico, aswell.

International cooperation in the neurotoxicologyfield is very limited. Neurotoxicological researchhas been primarily an intranational effort. In recentyears, some international cooperation has beeninitiated by WHO and the U.S. National ToxicologyProgram, but thus far this has only occurred inspecific areas, such as lead toxicity, solvent toxicity,and the development of testing methodologies. Thelimited scope of international cooperation is largelydue to the lack of funds available for such efforts.

In some European countries, notably the FederalRepublic of Germany and Sweden, environmentalmovements are becoming increasingly influential. Itis likely that in the future these governments willplay leading roles in supporting research and indeveloping regulations to control toxic substances.The Federal Republic of Germany has already actedto remove lead from gasoline and to fund studies oflead toxicity in children. All of the Scandinaviancountries have traditionally supported solvent re-search. This will likely continue and may broaden toinclude the investigation of other agents as environ-mental movements grow.

1.

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