From: Clifford, Wayne (DOH) Sent: Friday, February 05, 2010 9:33 AM To: christian.myrta@epa.gov Subject: Atrazine

Hello Myrta:

I know this is late, but just thought I would share with EPA our pesticide illness surveillance data on Atrazine. It does not appear to be sh owing up very much there. However, I would like EPA to know that ba sed on its prevalence in national water system data; its proclivity for dermal, or al, and inhalation routes; and my real concerns about its toxicity which I ha ve highlighted below from ATSDR’s Tox Profile, I support stronger restrictions, incl uding banning its use. I am particularly concerned about protection of the nation’s groundwater as that seems to be the major US population exposure.

Please pass this along to SAP members.

Thanks!

There is no direct information on the toxicityof atrazine in children and no information on effects in adults who were exposed as ch ildren. A single cohort study of farm couples in Canada indicated that atrazine exposure may be asso ciated with increased preterm delivery and miscarriage (Arbuckle et al. 2001; Sa vitz et al. 1997), and an ecological study indicated that atrazine levels in dri nking water were positively associated with decreased intrauterine growth rates and increased birth defects in the respective communities (Munger et al. 1992b, 1997).

Animal data indicate that the primary ta rget of atrazine is the reproductive systemand that atrazine can affect adult animals, which may result in effects in the offspring. Male rats exposed to 25, but not 12.5, mg/kg/day atrazine via lactation on postpartum days 1–4 had inflammation of the lateral prostate at 120 days of age (Stoker et al. 1999). This effect was thought to be the result of a lack of prolactin release in the dam in response to pup suckling, which was verified by monitoring plasma prolactin levels during and after pup suckling. Also, co-administr ation of ovine prolactin wi th atrazine to the dam eliminated the increase in prostate infl ammation in offspring. Prolactin plays an important role in the postn atal development of the t uberoinfundibular dopaminergic (TIDA) system, which, in the adult rat, has an inhibitory effect on prolactin release from the pituitary (Shyr et al. 1986). A lack of pr olactin during development results in a lack of prolactin release control and hyperprolac tinemia in the adult rats, which leads to lateral prostate inflammation (T angbanluekal and Robinette 1993).

Peruzovi ć et al. (1995) found subtle neurobehavioral effects (increased spontaneous activity in females and increased performance in avoidance conditioning trials in males) in offspring of rat dams exposed to 120 mg /kg atrazine 6 times during a 12-day period that ended 4 weeks before the rats were bred. The mechanism for this effect is unknown,but since atrazine is not thought to persist in tissues, it ma y be mediated through changes in the dam that later affect the offspri ng. These data indicate that the developing organism may be susceptible to the eff ects of atrazine and/or its metabolites.

There are no studies that indi cate that metabolism of atrazi ne differs between children and adults or between young and adult animal s. The primary pathway by which atrazine is metabolized is dealkylation to yield the mono- and/or didealkylated atrazine derivatives. In vitro studies with human liver microsom es and recombinant cytochrome P-450 (CYP) isozymes indicate that multiple CY P isozymes are probably involved in the dealkylation of atrazine in humans (Lang et al. 1997). This study i ndicates that CYP1A2, CYP2C19, and CYP1A1 may be the major CY P enzymes for atrazine, but that other forms, including CYP2A6, CYP2C9, and CYP2 B6, are likely to be major contributors, especially in individuals with low levels of CYP2C19 or CYP1A2. While CYP2C19 and CYP1A2 are not present in appreciable leve ls in human fetal liver, their activities increase to adult levels by 4–6 months of age (Leeder and Kearns 1997; Ratenasavanh et al. 1991; Sonnier and Cresteil 1998). These data i ndicate that infants, at or shortly after birth, are capable of metabolizing atr azine to its dealkylated metabolites. An association was found between Iowa communities exposed to an average of 2.2 μ g/L atrazine in the drinking water in 1984–1990 and an increased risk of intrauterine gr owth retardation and cardiac, urogenital, and limb reduc tion defects (Munger et al. 1992b, 1997).

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__________________________________________________________________ Wayne Clifford, Manager Office of Environmental Health, Safety, and Toxicology Pesticide Illness and Zoonotics Disease Surveillance and Prevention Washington State Department of Health