1. Lindane: An Organochlorine Pesticide Pesticide Health Effects Medical Education Database (PHEMED 2010)

2. About Organochlorine Pesticides Organochlorines … Are chlorinated synthetic organic molecules which may contain sulfur as well Tend to be fat soluble Are readily absorbed from the gastrointestinal tract and to a lesser degree, through the skin Have a wide range of acute & chronic health effects Are categorized as Persistent Organic Pollutants (POPs) meaning they persist in the environment and accumulate in tissues of living organisms

3. A little history … Most organochlorines have been banned in the United States because of their long half lives. The most notorious organochlorine, DDT, was banned in the US 1972. Others that have been banned since then include: aldrin, dieldrin, heptachlor, toxaphene and chlordane. Organochlorines still in use include lindane, dicofol, methoxychlor, and pentachorophenol; endosulfan will be in use until current supplies are exhausted.

4. Lindane is used to … Protect crop seeds from insects Control pests and ticks in forests, on pets and livestock Control ants and other household pests Control lice and scabies in humans

5. Lindane Regulations In the US … The Environmental Protection Agency (EPA) banned Lindane for agricultural uses in 2006. The Food and Drug Administration allowed Lindane in pharmaceutical products (such as shampoos and lotions) by prescription EPA approved the cancellation of Lindane effective Oct 1 2009 Lindane is likely to be found in homes for a few years Globally… In May 2009, the Stockholm Convention on Persistent Organic Pollutants issued a provision that included Lindane in a list of pollutants to be phased out.

6. Pesticide Health Effects Medical Education Database (PHEMED) Symptoms of Lindane Toxicity

7. Toxicology of Organochlorines Exposure occurs through ingestion, inhalation and dermal absorption. Gastrointestinal and dermal absorption is enhanced by the presence of fats. Organochlorines tend to be stored in fat tissue, Lindane to a lesser extent than others. Excretion: oThe chief route of excretion is biliary oNearly all organochlorines yield urinary metabolites The primary toxic action occurs on the central nervous system causing hyperexcitability

8. Array of Symptoms Associated with Lindane Poisoning Convulsions Cough Dizziness Headache Nausea and vomiting Tremors Ataxia Muscular weakness Paraesthesias of face, tongue and extremities May also cause eye, ear, nose, throat or dermal irritation and severe respiratory problems such as respiratory depression

9. Typical Order of Symptom Occurrence: Organochlorine Poisoning Symptoms begin to appear about 20 minutes to one hour after exposure The progression of symptoms depends on dose and susceptibility of affected person Source: Carl Zenz, Occupational Medicine, 3 rd. Ed.., St. Louis: Mosby 1994 Nausea Vomiting Restlessness Tremor Apprehension Convulsions Coma Respiratory Failure Death

10. A Few Facts About Lindane Poisoning with Lindane … Most probable route is ingestion … though Lindane is efficiently absorbed through the skin, especially abraded skin. Should not be used by … opregnant or nursing women oinfants opersons with excoriated skin opersons with seizure disorders

11. Pesticide Health Effects Medical Education Database (PHEMED) Diagnosing Lindane Poisoning

12. Blood, tissue and urine determinations of organochlorine pesticides are available from a limited number of laboratories; however, this testing is rarely useful for Lindane because of its rapid Metabolism.

13. Diagnosing Lindane Poisoning: Health History The health and exposure history is the primary means to identify Lindane (and other pesticides) as the cause of symptoms. The history should determine: oThe name of the pesticide product used (for Lindane – lotion, cream or shampoo) oRoute of exposure (oral, skin, inhaled, eye) oThe amount of the substance ingested, inhaled or absorbed oCircumstance of exposure – intentional or accidental oHow did it happen? oWhat actions have been taken (e.g., home remedies)?

14. Lindane Poisoning: A Differential Diagnosis The common symptoms of Lindane poisoning may be confused with many other conditions such as: Brain infections Meningitis Viral infections Food poisoning And many more…. Laboratory studies to rule out other causes of symptoms may include: oElectrolytes, oRenal panel oLiver function tests oArterial blood gas oUrinalysis Imaging studies may include: oChest or abdominal radiography oCT scan oLumbar puncture Other tests oElectroencephalogram

15. Chronic Problems Associated with Lindane and other Organochlorines Studies that have explored possible correlations include: –Various types of cancer (Xu X et al., 2010; Chiu BC et al., 2009; Purdue M, 2007) –Neurological damage (several organochlorines are known neurotoxins) (Kamel F et al., 2005; Mladenovic D et al., 2010) –Parkinson's disease (Corrigan, FM, 2000; Hammond DB et al. 2008) –Respiratory illness (Valcin M. et al., 2007) –Birth defects (Fernandez, MF et al., 2007; Matsuura, I, 2005; Pierik, FH et al., 2007) –Abnormal immune system function (Farr SL et al., 2004)

16. Other Facts about Lindane* Lindane has been a second line treatment for scabies and lice. Alternatives include pyrethrins & permethrins. Available products should be limited and will become more scarce as time goes on. Most serious adverse events are related to misuse of prescription Lindane. *http://www.fda.gov/Drugs/DrugSafety/PublicHealthAdvisories/UCM052201

17. Pesticide Health Effects Medical Education Database (PHEMED) Treatment of Organocholorine Poisoning

18. First Aid Measures Ingestion: oRinse Mouth oDo not induce vomiting (patient may aspirate) oGive plenty of water to drink Dermal exposure: oRemove any contaminated clothing; oWash skin Refer for medical attention

19. Treatment for Lindane (and other organochlorine) Poisoning If the pesticide has been ingested … –Gastric lavage with 2 to 4 liters of tap water –follow with saline purgative (30 gram sodium sulfate in 250 mL water) To control restlessness and/or convulsions … –Barbiturate or diazepam IM or IV in appropriate dosage –Make sure patient is physically safe Mechanical respiratory assistance with oxygen if needed

20. Treatment (continued) If severely poisoned, monitor cardiac status and pulmonary ventilation DO NOT GIVE epinephrine or other adrenergic amines. The heart is also hyperexcitable. DO NOT GIVE vegetable oils or fats by mouth (enhanced GI absorption)

21. Follow-up Considerations After 6 hours of observation, determine if patient needs to be admitted or sent home. Survey for on-going home, school or work exposure Instruct patient and/or family regarding safe storage of pesticides Provide verbal and written information about pesticide poisoning

22. References Chiu, BC & Blair, A (2009). Pesticides, chromosomal aberrations, and non- Hodgkins lymphoma. Journal of Agromedicine, 14(2)250-255. Corrigan, FM et al. (2000). Organochlorine pesticides in substantia nigra in Parkinson’s disease. Journal of Toxicology and Environmental Health, 59(4):229-234 Farr SL et al. (2004). Pesticide use and menstrual cycle characteristics among premenopausal women in the Agricultural Health Study. American Journal of Epidemiology, 160(12):1194-204.) Fernandez, MF et al. (2004). Human exposure to endocrine-disrupting chemicals and prenatal risk factors for cryptorchidism and hypospadias: a nested case- control study. Environmental Health Perspectives, 15 Suppl 1:8-14. Hammond DB et al. (2008). Pesticide exposure and risk of Parkinson's disease: a family-based case-control study. BMC Neurology 8:6. Kamel F, et al. (2005). Neurologic Symptoms in Licensed Private Pesticide Applicators in the Agricultural Health Study. Environmental Health Perspectives 113:877–882. Matsuura, I et al., (2005). Evaluation of a two-generation reproduction toxicity study adding endpoints to detect endocrine-disrupting activity using lindane. Journal of Toxicology Science, 30 Spec No.:135-161.

23. References (continued)… Mladenovic, D et al., (2010) The correlation between lipid peroxidationin different brain regions and the severity of lindane- induced seizures in rats. Molecular Cellular Biochemistry, 333(1-2):243-50. Pierik FH et al Maternal pregnancy serum level of heptachlor epoxide, hexachlorobenzene, and beta-hexachlorocyclohexane and risk of cryptorchidism in offspring. (2007). Environmental Research, 105(3):364-9. Purdue M. (2007). Occupational exposure to organochlorine insecticides and cancer incidence in the Agricultural Health Study. International Journal of Cancer. 1;120(3):642-9. Valcin M, et al. (2007). Chronic bronchitis among nonsmoking farm women in the agricultural health study. Journal of Occupational Environmental Medicine, 49(5):574-83.] Xu, X,et al. (2010). Association of serum concentrations of organochlorine pesticides with breast cancer and prostate cancer in U.S. adults. Environmental Health Perspectives, 118(1):60-66