1. Children’s Vulnerability to Pesticides Children’s Vulnerability to Pesticides Photo: H Murphy – Alahanpanjang, West Sumatra Indonesia, 1996

2. Why? Behavioral factors Behavioral factors Biological factors Biological factors Bigger doses Bigger doses Long term effects @ low level exposure Long term effects @ low level exposure

3. Sources – Child/OP Encounters > ¼ mi

4. Proximity to Farmland Data from Washington State PNASH Center Research Lu C, Fenske RA, Simcox NJ, Kalman D. Pesticide exposure of children in an agricultural community: evidence of household proximity to farmland and take home exposure pathways. Environ Res. 2000 Nov;84(3):290-302.

5. Child Behavior Question CDC reports from a nationally representative sample of the U.S. population shows that children have twice the amount of pesticide by- products in their urine as adults. How would you describe to a parent the behaviors in young children that would explain this?

7. Behaviors Hand to mouth: Taste their environment Hand to mouth: Taste their environment Near the ground: Spend more time on the ground Near the ground: Spend more time on the ground Outdoors: Spend more time outside Outdoors: Spend more time outside

8. Agricultural Workplace/Playground

9. Geometric Means (µmol/L) and 95% C.I. for OP Metabolite Concentrations by Sampling Month (Arrows indicate months of OP pesticides spraying) Koch D, Lu C, Fisker-Andersen J, Jolley L, Fenske RA. Temporal association of children's pesticide exposure and agricultural spraying: report of a longitudinal biological monitoring study. Environ Health Perspect. 2002 Aug;110(8):829-33.

10. Behavior: soil ingestion 2.5 year old Adult Soil ingestion (mg/day) Indoor5020 Outdoor600.4 G. Selevan. EHP 2000;108 Suppl 3:451-455

11. Child Biology Question Maria’s husband is an applicator but his blood test (cholinesterase monitoring program) is normal. She likes to take her baby with her when she picks him up from work but was advised against this. She cannot understand why being around pesticides would be a problem for her baby when her husband who had direct contact is fine. How would you explain to a parent the biological factors would make a child more vulnerable than an adult?

12. Biology- Higher Dose By: 1.Higher Metabolic Rates Inhales more per day (1.7x) than adultInhales more per day (1.7x) than adult 2.Dietary consumption/body weight Drinks 2 x more water per their weight than an adultDrinks 2 x more water per their weight than an adult Eats 12x more apples per their weight than an adultEats 12x more apples per their weight than an adult 3.Skin More permeable: highest at birthMore permeable: highest at birth 2.7 x more skin surface/weight than adults2.7 x more skin surface/weight than adults 4.Developing organs

13. Biology: inhalation dose Age (years) Weight (kg) Inhalation Rate (m 3 /day) “dose” (m 3 per kg per day) <17.64.50.592 1-2136.80.523 3-5188.30.461 6-826100.385 9-1136140.389 12-1450150.300 15-1766170.258 1.7x

14. Biology: dermal & dietary dose Newborn Young Child Older Child Adult Surface area: body mass ratio (m 2 /kg) 0.0670.0470.0330.025 < 1 year 1-10 years 11-19 years 20-64 years Drinking water (tap) mean intake (ml/kg/day) 43.535.518.219.9 < 1 year 3-5 years 12-19 years 40-69 years Fruit consumption (g/kg/day) Citrus1.92.61.10.9 Apples5.03.80.40.4 G. Selevan. EHP 2000;108 Suppl 3:451-455 12x 2.7 x 2x

15. Biology: skin permeability Skin permeability Skin permeability Highest at birth Adult permeability by ~ 1 yr.

16. Vulnerability to Health Effects: Organs Still Developing  Neurological  Reproductive  Pulmonary  Renal  Skeletal  Immune  Metabolism  GI tract “A little kid goes from a single cell to a laughing, sociable, intelligent, friendly human being over the course of two years. That’s dramatic growth and development!” Kenneth Olden, PhD, former Director, National Institute of Environmental Health Sciences

17. Metabolic Vulnerability: e.g. Paraoxonase Paraoxonase (PON1) is an enzyme that acts as a detoxifying system for organophosphate pesticide metabolites Activity of the enzyme is reduced in pregnancy, infancy, childhood Some evidence that PON1 activity can modify risk of adverse health outcomes in children birth outcomes (head circumference) pediatric brain tumors pediatric brain tumors Nielsen SS. Risk of Brain Tumors in Children and Susceptibility to Organophosphorus Insecticides: The Potential Role of Paraoxonase (PON1). EHP 2005;113:909-913 Berkowitz GS. In Utero Pesticide Exposure, Maternal Paraoxonase Activity, and Head Circumference. EHP 2004;112:388-391.

18. Parent Activities Question Ramon and Rosa’s 3 year old has small amounts of OP’s in his urine (he was recruited for a PNASH study). They are asking you how this could occur. The family live 5 miles from the closest orchard. Why is this? What things are the parents doing that would account for this? What questions will you ask and what things will you look for in the household

19. Dependency Children rely on adults to provide safe environments – indoor and out Children rely on adults to provide safe environments – indoor and out

20. Sources – Child/OP Encounters > ¼ mi

21. Parental Take-Home

22. Washington State data from PNASH: metabolites of OPs in children’s urine Applicator Community Low/Hi Spray Season Farmworker Seattle Fenske RA, Lu C, Curl CL, Shirai JH, Kissel JC. Biologic monitoring to characterize organophosphorus pesticide exposure among children and workers: an analysis of recent studies in Washington State. Environ Health Perspect. 2005 Nov;113(11):1651-7.

23. Parent Activity Questions Source of food and water Source of food and water Parent occupation? Parent occupation? Shower after working before holding children? Shower after working before holding children? Work clothes and shoes in the house? Work clothes and shoes in the house? Laundry practices ? Laundry practices ? Use household pesticides ? Use household pesticides ? Garden pesticides ? Garden pesticides ? House and car cleaning ? House and car cleaning ? Pesticide storage? Pesticide storage? Location of day care? Location of day care? House near fields? House near fields?

24. Chlorpyrifos Metabolite Concentrations in the Urine of 22 Children Before, During, and After Organic Diet Intervention Conventional diet Organic diet Conventional diet Lu C, Toepel K, Irish R, Fenske RA, Barr DB, Bravo R. Organic diets significantly lower children's dietary exposure to organophosphorus pesticides. Environ Health Perspect. 2006 Feb;114(2):260-3.

25. Impacts on Children Studies on low level OP exposures among children The younger the child the greater consequences of OP exposure on development The younger the child the greater consequences of OP exposure on development Fetus Fetus Soon after birth Soon after birth Nerve cells affected Nerve cells affected Levels so low that they do not affect the cholinesterase but still damage developing nerve cells. Levels so low that they do not affect the cholinesterase but still damage developing nerve cells.

26. Virginia Rauh, Robin Wyatt, Frederica Perera Columbia University Mary Wolff, Stephanie Engel, Gertrud Berkowitz Mount Sinai School of Medicine Brenda Eskenazi, Kim Harley, Asa Bradman, Amy Marks University of California, Berkeley What is the Evidence? Three Studies of Mother-Baby Pairs

27. New York Studies New York Studies Following 700 mother/baby pairs for 7 years. Following 700 mother/baby pairs for 7 years. Mother’s air intake for pesticides Mother’s air intake for pesticides Mother’s blood Mother’s blood Umbilical cord blood of baby Umbilical cord blood of baby Followed 409 mother/baby pairs for 3 years. Followed 409 mother/baby pairs for 3 years. Mother’s urine Mother’s urine Birth outcomes Birth outcomes Development to age 2 Development to age 2

28. California Studies 600 pregnant Latina women from working families living in Salinas, a heavy agriculture area. 600 pregnant Latina women from working families living in Salinas, a heavy agriculture area. OP by-products in urine during pregnancy and after delivery OP by-products in urine during pregnancy and after delivery Birth outcomes Birth outcomes

29. Biomarkers of Prenatal OP Pesticide Exposures Berkeley Mt. Sinai Columbia OP by products ( Dialkyl Phosphates) X Chlorpyrifos X In UrineIn Blood Source: Source: Kim Harley, PhD UC Berkeley Center for Children’s Environmental Health Research

30. Early Childhood Neurodevelopmental Outcome Measurements Berkeley Mt. Sinai Columbia Neonatal X 3Y X 2Y X 1Y X 6M X Infant Development* Behavioral Assessment Pre-school Intelligence** 3.5Y X 5Y X **** X **** Verbal IQ assessed with PPVT **Wechsler Preschool and Primary Scale of Intelligence (WPPSI) * Baley: Tests motor, cognitive, language development Source: Source: Kim Harley, PhD UC Berkeley Center for Children’s Environmental Health Research *** Brazelton

31. Early Childhood Behavioral Outcome Measurements Berkeley Mt. Sinai Columbia Child Behavior Checklist 3Y X 2Y X 3.5Y X Source: Source: Kim Harley, PhD UC Berkeley Center for Children’s Environmental Health Research

32. URBAN NEW YORK AGRICULTURAL CALIFORNIA Source: Source: Kim Harley, PhD UC Berkeley Center for Children’s Environmental Health Research

33. Race/Ethnicity Non-Hispanic White African-American Hispanic Other Married < High school Berkeley (%) 1 -- Mexican 97 2 82 81 Mt. Sinai (%) 20 27 Mex, PR 51 1 29 32 Columbia (%) -- 35 Dominican 65 -- 29 35 Characteristics of Study Populations Source: Source: Kim Harley, PhD UC Berkeley Center for Children’s Environmental Health Research

34. In summary… Three scientifically-rigorous, cohort studies Three scientifically-rigorous, cohort studies Different populations Different populations Different exposure levels and sources Different exposure levels and sources Exposure measured using biomarkers in urine (metabolites) and blood (parent compound) Exposure measured using biomarkers in urine (metabolites) and blood (parent compound) Despite these differences, some patterns emerge… Despite these differences, some patterns emerge… Source: Source: Kim Harley, PhD UC Berkeley Center for Children’s Environmental Health Research

35. Prenatal OP exposure associated with …….. Increased odds of abnormal reflexes in neonates Increased odds of abnormal reflexes in neonates Poorer mental development in 2 and 3 year olds Poorer mental development in 2 and 3 year olds Poorer verbal IQ in 3½ and 5 year olds Poorer verbal IQ in 3½ and 5 year olds Increased odds of pervasive developmental disorder Increased odds of pervasive developmental disorder Source: Source: Kim Harley, PhD UC Berkeley Center for Children’s Environmental Health Research