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 showing up very much there. 

However, I would like EPA to know that based on its prevalence in national water 

system data; its proclivity for dermal, oral, and inhalation routes; and my real 

concerns about its toxicity which I have highlighted below from ATSDR’s Tox 

Profile, I support stronger restrictions, including 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 toxicity of atrazine in children and no information 

on effects in adults who were exposed as children. A single cohort study of farm couples 

in Canada indicated that atrazine exposure may be associated with increased preterm 

delivery and miscarriage (Arbuckle et al. 2001; Savitz et al. 1997), and an ecological 

study indicated that atrazine levels in drinking 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 target of atrazine is the reproductive system and 

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-administration of ovine prolactin with atrazine to the dam 

eliminated the increase in prostate inflammation in offspring. Prolactin plays an 

important role in the postnatal development of the tuberoinfundibular 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 prolactin during development results in a lack 

of prolactin release control and hyperprolactinemia in the adult rats, which leads to 

lateral prostate inflammation (Tangbanluekal and Robinette 1993). 

Peruzović 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 may be mediated through changes 

in the dam that later affect the offspring. These data indicate that the developing 

organism may be susceptible to the effects of atrazine and/or its metabolites. 

There are no studies that indicate that metabolism of atrazine differs between children 

and adults or between young and adult animals. 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 microsomes and recombinant cytochrome 

P-450 (CYP) isozymes indicate that multiple CYP isozymes are probably involved in the 

dealkylation of atrazine in humans (Lang et al. 1997). This study indicates that CYP1A2, 

CYP2C19, and CYP1A1 may be the major CYP enzymes for atrazine, but that other 

forms, including CYP2A6, CYP2C9, and CYP2B6, 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 levels 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 indicate that infants, at or shortly after 

birth, are capable of metabolizing atrazine to its dealkylated metabolites. An association 

was found between Iowa communities exposed to an average of 2.2 μg/L atrazine in the 

drinking water in 1984–1990 and an increased risk of intrauterine growth retardation and 

cardiac, urogenital, and limb reduction 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