PESTICIDES AND CHILDREN as a Susceptible Population J. Routt Reigart, MD Professor of Pediatrics Medical University of South Carolina

Children Are Different 1. Exposure patterns are different Diet Skin Air Behaviour 2. Susceptibility is different Critical periods of development Lifelong alteration of function and structure

DIET Caloric intake of children less than one year of age 100 Cal/Kg Equivalent for 70 Kg adult is 7000 Calorie diet Fluid intake of children less than one year of age 150-200 Ml/Kg Equivalent for 70 Kg adult is 10.5-14 liters per day

DIET NAS Report “Pesticides in the Diets of Infants and Children” (1993) Children differ quantitatively and qualitatively in dietary consumption patterns Simulation of food and juice exposure to organophosphates 4.1% of children each day exceeded reference dose

FOOD QUALITY PROTECTION ACT “Aggregate” is risk from all exposures: dietary, water, residential “Cumulative” adds risk from all chemicals with common mechanism of toxicity Application of this law illustrated that non-dietary exposures often overwhelm dietary exposures

SKIN Children’s skin is often more exposed Children are lower to the ground and low-growing plants Children spend more time actually on the ground Ratio of skin surface area to body weight very high in children Ability of skin to protect a developmental task

SKIN SURFACE AREA

AIR LUNG CAPACITIES

Air Breathing Rates By Age

BEHAVIOUR Hand-to-mouth and object to mouth Floor and ground play High activity levels Low to the ground Variable diet and food choices

Diethylstilbesterol DES Before 1971 5-10 million Americans exposed via pregnancy use Major reported effects on fetus 1:1000 females estimated to get clear cell adenocarcinoma relatively early in life

DES Multiple structural abnormalities in female and probably in male offspring. Estimates up to 69% of an exposed female cohort Dose related risk but no consensus opinion on threshold Mode of action for cancer clearly different for fetus vs. adult. Not mutagenic.

DES Mortality and morbidity from cancer clearly unacceptable on public health basis. Morbidity from malformations also unacceptable. Mechanism of carcinogenesis most likely different in fetus from adult. Must consider mode of action for fetus in risk assessment process.

Atrazine Breast tumors in Sprague-Dawley rats Mode of action thought to be hypothalamic suppression of gonadotrophin releasing hormone Decreased GnRH leads to decreased LH, resulting in prolonged secretion of estrogen and prolactin Persistent estrus

Atrazine Humans- weak possible association between triazines and cancer Ovary, Breast, Prostate Atrazine likely alters hypothalamic function in primates and humans Mode of action less plausible in primates and humans

Atrazine In children atrazine may lead to a variety of non-cancer human health effects, but not a cancer risk Most likely effect is delayed puberty

MIREX Very persistent though production ceased 1976 Bioaccumulated and biomagnified in aquatic and terrestrial food chains Though not observed in humans, cataracts can be produced in rats and mice by exposure between one and eight days postpartum

METHOXYCHLOR Relatively short lived in the environment though is an organochlorine Rapidly metabolized in human and animals In animals adversely affects development of female reproductive system, early onset of estrus, uterotrophic, mammary gland hyperplasia. In male animals, testicular and prostatic atrophy. Decreased sperm counts.

PCB’s Highly persistent organic pollutants Behavioral abnormalities observed in young children over a wide range of exposure Effect from intrauterine and perhaps breast fed infants Widespread contamination, very variable levels Bioaccumulate, particularly in fish Effects seen with wide range of species, including primate models

TOXAPHENE ATSDR list fetus, nursing babies, and very young children as particularly susceptible Potential for alteration of reproductive physiology Immature enzyme detoxification Placental and milk transfer Adverse behavioral response in offspring exposed in utero (animal) Histopathology in fetal liver, thyroid, and kidneys (animal)