Chlorpyrifos ENV H 572 Hilary Zetlen Chlorpyrifos Organophosphate pesticide Marketed by Dow Chemical since 1965 Domestic and agricultural uses 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 Annual use, Lbs. (% crop treated) 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 Stakeholders Dow Chemical Corp. and pesticide manufacturers Agribusiness, small farmers, and agricultural communities Consumers Government agencies The environment Hazard Identification What is it? White crystalline solid Synthesized from 3methylpyridine Hydrophobic; often applied dry or in an oil/solvent suspension Frequently marketed as Dursban/Lorsban 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 Acetylcholinesterase Inhibition 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! 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 Dose-Response Assessment Child ingestion in an agricultural setting 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 IRED Human Health Assessment 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 Exposure Assessment 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 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 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 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/m3 24 hours after pesticide application 60 times higher than EPA limit! 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. Precautionary Assessment Community / Social Issues Parameter Score Goal 2 Need 2 Future Generations 3 Democratic, community based process 2 Alternatives 3 Total 12/15 Exposure Issues Exposure Issues Exposure 3 Multiple exposures 3 Children exposed 5 Consumer products 3 Occupational exposure Food exposure Total 3 3 20/20 Hazard/Toxicity Hazard 9 Individual Sensitivity 3 Ecological hazard 3 Volume 5 Persistent 1 Bioaccumulation 2 Uncertainty 2 Total 25/30 Risk Management Risk Perception “Pesticide Drift” and children in California 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 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 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 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. 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 Questions?