toxicology

ARSENIC TOXICITY

Sources

Moods of exposure

Toxicokinetics

Mechanisms of toxicity

Symptoms of acute and chronic toxicity

Diagnosis

Treatment

Notable cases of arsenic poisoning

References

OUTLINES

SOURCES

MOODS OF

EXPOSURE

1- INGESTION:

ARSENIC CONTAINING FOODS:

2- INHALATION:

3- SKIN:

TOXICOKINETICS

.

ABSORPTION

DISTRIBUTION

METABOLISM

EXCRETION

MECHANISMS OF

TOXICITY

ARSENIC-INDUCED

CARDIOVASCULAR DYSFUNCTION

ARSENIC-INDUCED DIABETES

MELLITUS

.

ARSENITE-INDUCED NEUROTOXICITY

ARSENIC-INDUCED NEPHROTOXICITY

AND HEPATOTOXICITY

ARSENIC-INDUCED

CARCINOGENICITY

SYMPTOMS OF ACUTE

AND CHRONIC

TOXICITY

SYMPTOMS OF CHRONIC ARSENIC POISONING

Affected organ Features

Skin Excessive darkening of skin

(hyperpigmentation) in areas that are not exposed to sunlight

Excessive formation of scaly skin on the palms and soles (arsenical keratosis)

Exfoliative dermatitis Arsenic-induced skin cancers (especially

Bowen disease , Squamous cell carcinoma)

Nails Transverse white bands of arsenic deposits

across the bed of the fingernails (Mee'slines)

Hair Arsenic deposits in hair

Nervous system Sensory changes, numbness and

tingling in a “stocking-glove”

distribution (sensory peripheral

neuropathy)

Headache, drowsiness, confusion

Distal weakness of small muscles

e.g. hands and feet

Blood and urine Haemolytic anaemia (moderate) Leukopaenia (low white cell count) Proteinuria (protein in urine)

Other Inflammation of respiratory mucosa

Peripheral vascular insufficiency

Increased risk of cancer of lung, liver,

bladder, kidney and colon

Features of acute arsenic poisoning

Symptoms usually start within 30 minutes to 2 hours. Acute arsenic ingestion is typically followed by a severegastroenteritis, garlic odour and hypersalivation. There is a characteristic sequence of multi-organ failure,with: neurological symptoms (within hours) and cardiacfeatures, succeeded by adult respiratory distresssyndrome and renal/liver dysfunction.Marrow suppression develops after a few days to weeks insurvivors, as does alopecia and an ascending motorneuropathy.

often present in breath and body tissues

Hypersalivation, abdominal pain, vomiting, diarrhoea leading to hypovolaemic shock.

Trivalent arsenic is corrosive - may cause oral burns, dysphagia and GI bleeding.

Myocardial depression.

Dehydration, hypovolaemia or shock.

ECG changes including ST segment changes, prolonged QT interval, ventricular

tachycardia, torsades de pointes and ventricular fibrillation.

Gangrene of extremities.

Pulmonary oedema, adult respiratory distress syndrome and acute respiratory failure.

Inhaled arsenic causes irritation, bronchospasmand pulmonary oedema

Haematuria or haemoglobinuria (from acute haemolysis), proteinuria, acute tubular

necrosis with acute renal failure.

Jaundice, hepatomegaly, pancreatitis

CNS depression, encephalopathy and coma.

Seizures.

Acute haemolysis.

Bone marrow suppression.

Basophilic stippling and rouleaux formation may be seen on a blood film

Rashes

DIAGNOSIS

TREATMENT

1-TREATMENT OF ACUTE

ARSENIC:

2-TREATMENT OF CHRONIC

ARSENIC

1-Chelation 2-Nutrition 3-Removal

Chemical and synthetic methods are used to treat arsenic poisoning. Dimercaprol and dimercaptosuccinic acid are chelating agents that sequester the arsenic away from blood proteins and are used in treating acute arsenic poisoning. The most important side effect is hypertension. Dimercaprolis considerably more toxic than succimer.[citation needed]DMSA monoesters, e.g. MiADMSA, are promising antidotes for arsenic poisoning. Calcium sodium edetate is also used.

Supplemental potassium decreases the risk of experiencing a life-threatening heart rhythm problem from arsenic trioxide.

Various techniques have been evolved for arsenic removal, most frequently using absorbents such as activated carbon, aluminiumoxide, co-operative with iron oxide to form sludges, adsorption onto iron-oxide-coated polymeric materials, and electrocoagulation by nanoparticle. To remove the stress of heavy and toxic metals, an environment-friendly approach must be applied and the use of naturally occurring microbe must be emphasized. Bacteria, yeast, fungi, algae—all of them can be used for remediation processes and it is always recommended that microbe used for bioremediation must have natural decontamination process and the method should be cost-effective.

NOTABLE CASES OF

ARSENIC POISONING

http://www.youtube.com/watch?v=W3Hvexu5SqM

STRAIN GFAJ-1 OF THE

HALOMONADACEAE,

ISOLATED FROM MONO

LAKE, CALIFORNIA,

THAT IS ABLE TO

SUBSTITUTE ARSENIC

FOR PHOSPHORUS TO SUSTAIN ITS GROWTH.

REFERENCE

http://www.atsdr.cdc.gov/csem/arsenic/docs/arsenic.pdf

http://toxsci.oxfordjournals.org/content/123/2/305.full

Agency for Toxic Substances and Disease Registry (2007)ToxGuide for Arsenic, USA: Centers for Disease Control and Prevention.

Agency for Toxic Substances and Disease Registry (2009) Case Studies in Environmental Medicine; Arsenic Toxicity, USA: Centers for Disease Control and Prevention.

WHO (2000) Air Quality Guidelines, 2 edn., Copenhagen, Denmark: WHO Regional Office for Europe.

American Conference of Governmental Industrial Hygienists (ACGIH). Documentation of the threshold limit values and Biological Exposure Indics. 5th ed. ACGIH, Cincinnati, OH, 1986.

Armstrong, C. W., Stroube, R. B., Rubio, T., and Beckett, W. S. Outbreaks of fatal arsenic poisoning caused by contaminated drinking water. Arch. Environ. Health 39, pp 274-279, 1984.

Axelson, O., Dahlgren, E., Jansson, C. D., and Rehnlund, S. O. Arsenic exposure and mortality. Acase reference study from a Swedish copper smelter. Br. J. Ind. Med. 35, pp 8-15, 1978.

Dr. D.n. Guha Mazumder, Chapter 4 : Diagnosis and treatment of chronic arsenic poisoning By. In editor. Diagnosis and treatment of chronic arsenic poisoning, : Institute of Post Graduate Medical; 2000. p.20

Steven Marcus. Medscape. Arsenic Toxicity treatment [serial on the Internet]. 2012 [cited 2014 Nov 23]. Available from: Copyright © 1994-2014 by WebMD LLC, MEDLINE database Web site: http://http://emedicine.medscape.com/article/812953-overview

Dr. D.n. Guha Mazumder, Chapter 4 : Diagnosis and treatment of chronic arsenic poisoning By. In editor. Diagnosis and treatment of chronic arsenic poisoning, : Institute of Post Graduate Medical; 2000. p.20

Steven Marcus. Medscape. Arsenic Toxicity treatment [serial on the Internet]. 2012 [cited 2014 Nov 23]. Available from: Copyright © 1994-2014 by WebMD LLC, MEDLINE database Web site: http://http://emedicine.medscape.com/article/812953-overview