ENDOSULFAN

1
ENDOSULFAN

• ENVS 531
• Sunitha Yerragodula

2
The Chemical, History and present status

• First Introduced by Hoescht, under the trade name
  Thiodan, in Germany.
• A chlorinated Hydrocarbon belonging to Cyclodiene
  subgroup.
• There are two different configurations, alfa and
  beta.
• Very few details are available on the production
  levels since its ban in the United states after
  1982.

3
Contd..

• The chemical name -6, 7,8,9,10-Hexahydro-6,9-metha
  no-2,4,3-benzodioxanthiepine-3-oxide.
• WHO classifies endosulfan in category
  2(moderately hazardous solid)
• The U.S. EPA classifies it as category 1b (highly
  hazardous) pesticide.
• Mainly applied to cash crops like tobacco,
  cashew, Tea.

4
Exposure

• Major route is through food contamination
• Skin contact or food residues are minor routes
• The most dangerous exposure is through
  application without follwing the required safety
  measures.

5
Environmental fate

• Immobile in soils, transformed in surface waters
  and soils via hydrolysis and biodegradation.

6
Metabolism

• Endosulfan is transformed into endosulfan sulfate
  and endosulfan diol, which further metabolized
  into endosulfan lactone, hydroxyether, and ether.
• Polar metabolites are polar
• Nonpolar metabolites form the minor portion.
• The conversion to endosulfan sulfate is not a
  detoxification reaction.

7
Excretion and elimination

• Half lives range between 1-7 days
• Renal and hepatic routes are the two major routes
  of excretion.
• Renal excretion is demonstrated in humans while
  hepatic excretion is seen in animals.
• Excretion is a dose dependant process.

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Mechanisms of action

• Most probable way of absorption is through
  passive diffusion.
• The lipophilic nature of endosulfan enables it to
  get deposited in fatty tissues initially and
  finally in liver and kidney.

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Mechanisms of toxicity

• Antagonistic effects on GABA mechanism.
• Leads to convulsions and uncontrolled excitation.
• Proven to be neurotoxic.
• Suspected to induce liver, kidney, and
  hematological toxicity.
• There is difference in susceptibility to effects
  between in males and females.

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Mechanisms of toxicity contd

• The high susceptibility of females may be due to
  low rate of elimination and greater accumulation
  of endosulfan residues.
• Extensive Studies are yet to be performed to
  prove the chemicals role in disrupting endocrine
  system.

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Toxic effects

• Death accidental or intentional ingestion.
• Systemic effects
• 1) Respiratory effects like hypoxia,
  dyspnea occur at high level acute exposures.
• 2) Cardiovascular efects like tachycardia,
  gastro intestinal effects, and hematological
  effects also occur at very high doses.

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Toxic effects contd

• Estrogenic effects Directly interacts with
  estrogen receptor.
• Neurotoxicity Long term brain damage may be
  expected following acute exposures.
• Developmental effects Daily intake of 5-10mg
  /day in rats during gestational periods caused
  skeletal damages in the fetuses.
• Carcinogenicity No studies avaiable to prove the
  carcinogenic efects of endosulfan

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Conclusions

• It is imperative that studies need to be
  undertaken to elucidate endosulfans genotoxic,
  reproductive and developmental effects on humans.
  Owing to the extensive use of endosulfan in
  developing countries such as India, more research
  proving its deleterious effects on human life is
  essential to impose a ban on the chemical.

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References

• 1. Hubert Martin, 1961. Guide to the Chemicals
  used in Crop Production, Publication 1093.
  Research Branch, Canada Department of
  Agriculture.
• 2. a)ATSDR Sep2000.Toxicological profile for
  endosulfan(Update). United States Agency for
  Toxic Substances and Disease Registry, Atlanta,
  GA.
• b) ATSDR April1993. Toxicological profile for
  endosulfan. United Sates Agency for Toxic
  Substances and Disease Registry, Atlanta, GA.

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References contd..

• 3. http//www.poptel.org.uk/panap/pest/pe-end.htm
• 4. Insecticides Action and Metabolism,
  R.D.OBrien, 1967.
• 5. Generations at Risk, Reproductive Health and
  the Environment. Ted Schettlet, M.D., M.P.H.,
  Gina Solomon, M.D., M.P.H., Maria Valenti, and
  Annette Huddle, M.E.S.

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References contd..

• 6. Vickie S. Wilson and Gerald A. Leblanc. (1997)
  Endosulfan Elevates Testosterone
  Biotransformation and Clearance in CD-1 Mice.
  Toxic. Appl. Pharmacol. 148, 158-168.
• 7. M. Anand, R.N. Khanna, and D. Misra. (1980)
  Electrical Acticity of Brain in Endosulfan
  Toxicity, Ind. J. Pharmac., 12 (4) 229-235.