1. Chlorpyrifos ENV H 572 Hilary Zetlen

2. Chlorpyrifos  Organophosphate pesticide  Marketed by Dow Chemical since 1965  Domestic and agricultural uses

3. Prevalent Use  Broad spectrum of applications  Treatment of crops, lawns, building materials.  10 million lbs. applied each year  Majority applied to corn (approx. 5.5 millions lbs. annually)  Commonly used for vegetables, tree fruit in Washington state  Home use canceled in 2000  Previously most commonly used residential pesticide  Limited to tightly controlled childproof mechanisms

4. Annual use, Lbs. (% crop treated)

5. Regulatory Standing  CERCLA  Reportable quantity of release = 1 lb.  Clean Water Act  Allowable level = 20 ug/ L  FDA  0.05-15 ppm on food  FIFRA / EPA  Currently undergoing registration review  NRDC / PAN requesting revocation of registration  Final decision in 2015

6. Stakeholders  Dow Chemical Corp. and pesticide manufacturers  Agribusiness, small farmers, and agricultural communities  Consumers  Government agencies  The environment

7. Hazard Identification

8. What is it?  White crystalline solid  Synthesized from 3- methylpyridine  Hydrophobic; often applied dry or in an oil/solvent suspension  Frequently marketed as Dursban/Lorsban

9. Organophosphate Pesticides  “Nerve agents”  Somewhat chemically similar to sarin, VX  Compounds of special concern to the EPA  Priority for review under Food Quality Protection Act  Cholinesterase inhibitors  Inhibits breakdown of acetylcholine  Major consequences throughout nervous system  Cognitive effects, among others

10. Acetylcholinesterase Inhibition

11. Chlorpyrifos Toxicity  Acute exposure  Numbness, headache, dizziness, nausea, difficulty breathing, loss of consciousness, convulsions, paralysis  Chronic exposure  Cognitive impairment, disorientation, depression, lack of coordination, speech difficulties  Other effects  Lack of evidence for carcinogenic effect  Possible endocrine disruptor!

12. Developmental Effects  Prenatal exposure  Significant growth deficits in length and birthweight, increase in birth defects  Neurotoxicity  Disruption of brain development at sub-acetylcholinesterase inhibiting levels  Early childhood effects  Measured umbilical cord blood concentrations at delivery  >6.17 pg/g “high exposure” group  Associated with significant psychomotor and cognitive delays at 36 months

13. Dose-Response Assessment Child ingestion in an agricultural setting

14. EPA Reference Dose  RfD = 0.003 mg/kg/day  Dow Chemical Company:  Sixteen human male volunteers ingested 0, 0.014, 0.03, or 0.10 mg/kg/day of chlorpyrifos  20 days at the low and mid dose; treatment of the high-dose group (0.1 mg/kg/day) discontinued after 9 days due to a runny nose and blurred vision in one individual  Mean plasma ChE in this group was inhibited by about 65%  UF = 10 for human variability  FQPA, 1996: additional UF of 10 for children and females <50 years old  “Low-to-mid confidence” in estimated RfD

15. IRED Human Health Assessment

16. Prenatal chlorpyrifos exposure  Average birthweight in “high exposure” cohort = 3.24 kg  Lowest observed umbilical plasma concentration = 6.17 pg/g  Average adult plasma volume = 3.0 L  3.0 L * (1.025 kg/L) / 70 kg = 42 g plasma/ kg body weight  42 g/kg * 3.24 kg = 136.22 g plasma/infant  (6.17 pg chlorpyrifos/ g plasma) * 136.22 g plasma = 840.48 pg/infant  So how many mg/kg?  840.48 pg/infant * (1 mg/1,000,000,000 pg) * (1 infant/3.24 kg) =  2.59 * 10 -7 mg/kg at birth!! – about 100 times smaller than EPA RfD  significant psychomotor and cognitive delays at 36 months

17. Exposure Assessment

18. Exposure Routes  Ingestion  Considered primary risk for Chlorpyrifos exposure for general population  Metabolites present in urine in 82% of US adults  Inhalation  Requires presence of aerosolized pesticides  Particular risk for applicators, mixer-loaders  Dermal  Occupational exposures  “Take-home” exposures

20. Agricultural workers and their families  Much higher concentrations of chlorpyrifos in home  Correlates with proximity to orchards/application zones  Accumulates on household surfaces, dust, dirt  Lingers after application

21. Chemical fate  Biological half-life  Approx. 10-30 hours  Metabolites excreted in urine  Soil half-life  60-120 days  Sensitive to sunlight, microbial digestion  Oxidation to chlorpyrifos oxon  Little burden in water supply  Indoor half-life  Estimated around 30 days  Accumulates on sorbant surfaces

22. Child vulnerability  Children living in agricultural homes:  Average of 0.52 ug chlorpyrifos/ pair of hands  Dermal dose  3% absorption / 3.24 kg newborn = 4.8 * 10 -8 mg/kg  Oral dose  Hand-to-mouth behavior  100% absorption / 3.24 kg newborn = 1.6 * 10 -4 mg/kg  Inhalation dose  30 ug/m 3 24 hours after pesticide application  60 times higher than EPA limit!

23. Risk Summary  EPA RfD: 0.0003 mg/kg/day for children  Prenatal exposure with significant developmental effects:  Approx. 2.59 * 10 -7 mg/kg at birth  Significant exposures arising from:  Agricultural communities  Drinking water  U.S. allowable lifetime dose = 20 ug/L  Current standards are woefully inadequate to prevent long-term developmental consequences.

24. Precautionary Assessment

25. Community / Social Issues ParameterScore Goal2 Need2 Future Generations3 Democratic, community based process2 Alternatives3 Total12/15

26. Exposure Issues Exposure3 Multiple exposures3 Children exposed5 Consumer products3 Occupational exposure3 Food exposure3 Total20/20

27. Hazard/Toxicity Hazard 9 Individual Sensitivity3 Ecological hazard3 Volume5 Persistent 1 Bioaccumulation2 Uncertainty2 Total25/30

28. Risk Management

29. Risk Perception  “Pesticide Drift” and children in California  http://www.npr.org/templ ates/story/story.php?story Id=123817702 http://www.npr.org/templ ates/story/story.php?story Id=123817702  Dow Chemical on Chlorpyrifos and kids  http://www.chlorpyrifos.c om/myths-vs-facts.htm

30. Registration review  Docket opened May 2009  Human health assessment  Public comment period July-September of this year  Scoping: lack of emphasis on developmental toxicology data!  Environmental/endangered species impact assessment  Public comment October-December 2013  Final registration decision in 2015

31. Recent regulatory action  New limitations to protect salmon, steelhead under Endangered Species Act announced in September 2009  Created in conjunction with the National Marine Fisheries Service  New labeling guidelines  Limitations on application: buffer zones, increased environmental monitoring, fish mortality data

32. References  Eskenazi, et al. Exposures of children to organophosphate pesticides and their potential adverse health effects.  Fenske, et al. Children's exposure to chlorpyrifos and parathion in an agricultural community in central Washington State.  Fenske, et al. Biologically based pesticide dose estimates for children in an agricultural community.  Fenske, et al. Potential exposure and health risks of infants following indoor residential pesticide applications.  Gore. Environmental Toxicant Effects on Neuroendocrine Function.  Griffin, et al. Oral and dermal absorption of chlorpyrifos: a human volunteer study.  Gurunathan, et al. Accumulation of chlorpyrifos on residential surfaces and toys accessible to children.  Rauh, et al. Impact of Prenatal Chlorpyrifos Exposure on Neurodevelopment in the First 3 Years of Life Among Inner-City Children.  Simcox, et al. Pesticides in household dust and soil: exposure pathways for children of agricultural families.  Slotkin and Seidler. The alterations in CNS serotonergic mechanisms caused by neonatal chlorpyrifos exposure are permanent.

33. Resources  EPA - Chlorpyrifos Fact Sheet: http://www.epa.gov/pesticides/reregistration/REDs/factsheets/chlorpyrifos_fs.htm  EPA - Chlorpyrifos Risk Information: http://www.epa.gov/iris/subst/0026.htm  EPA - Chlorpyrifos Interim Risk Management Decision: http://www.epa.gov/oppsrrd1/reregistration/chlorpyrifos/  ATSDR - Chlorpyrifos ToxFAQs: http://www.atsdr.cdc.gov/tfacts84.html  Pesticide Action Network – Chlorpyrifos: http://www.pesticideinfo.org/Detail_Chemical.jsp?Rec_Id=PC33392  National Agricultural Statistics Service - Agricultural Chemical Use Database: http://www.pestmanagement.info/nass/app_usage.cfm  National Resources Defense Council - Our Children At Risk: http://www.nrdc.org/health/kids/ocar/chap5b.asp  Dow Chemical - Chlorpyrifos Protects: http://www.chlorpyrifos.com/  NPR - "Pesticide drift eluding efforts to combat it", 2/28/10:http://www.npr.org/templates/story/story.php?storyId=123817702

34. Questions?