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Human Impacts


The United States Environmental Protection Agency is reviewing atrazine for reregistration and tolerance reassessment under the Federal Insecticide, Fungicide and Rodenticide Act ("FIFRA") and the Federal Food, Drug and Cosmetic Act as amended by the Food Quality Protection Act of 1996 ("FQPA"). EPA developed a human health risk assessment for atrazine as part of this review.

EPA's human health risk assessment concluded that human risk from exposure to atrazine in food is minimal. EPA believes that the primary risk of human exposure to atrazine comes from drinking water. Some drinking water may contain atrazine as a result of runoff from fields treated with atrazine.

EPA's human health risk assessment concluded that atrazine is not likely to cause cancer, based in large part on recommendations by EPA's Science Advisory Panel. EPA does not propose regulating atrazine and its metabolites on cancer risk. Instead, EPA proposes regulating atrazine and its metabolites on developmental end points.


In the late 1980s, EPA classified the carcinogenic potential of atrazine as "possible," category "C" under the cancer assessment guidelines issued in 1986. In 1994, EPA initiated a Special Review of atrazine's potential to cause human cancer through dietary or occupational exposure.

During the 1990s, EPA reviewed the available data and tentatively concluded that there may be a plausible mechanism of action for atrazine to cause cancer based on tumors in one strain of rat. EPA proposed reclassifying atrazine from "category C" to "likely human carcinogen" in accordance with terminology from proposed cancer guidelines.

EPA's proposal was rejected during peer review by the FIFRA Scientific Advisory Panel. In June 2000, the SAP determined that the mechanism that produced tumors in the rats was not relevant to humans and that the scientific evidence did not support classifying atrazine as a "likely human carcinogen." The SAP recommended that EPA classify atrazine as "not a likely human carcinogen."

EPA reviewed and accepted the SAP's conclusion on atrazine's cancer risk. EPA's current Human Health Risk Assessment uses a non-cancer endpoint as the basis for regulating atrazine exposures.

The Natural Resources Defense Council has for years argued that atrazine causes cancer, and has actively lobbied EPA to regulate atrazine on a cancer endpoint. Disappointed with the SAP and EPA conclusion that atrazine is not likely to cause cancer, NRDC recently petitioned EPA to reconsider its conclusion and to ban atrazine. NRDC's petition is based in large part on a study conducted by atrazine producer Syngenta at one of its plants in Louisiana. This Syngenta study showed an increase in prostate cancer among workers at the plant due to screening bias. Syngenta screened all its male workers for prostate cancer and if the same screening had been applied to all persons in the state, then essentially the same result would have occurred.

EPA has not yet acted on NRDC's petition. EPA is reviewing additional data on the prostate cancer study. The cancer issue will probably be addressed by EPA in an Interim Registration Eligibility Decision ("IRED") scheduled for release in January 2003.

CRE Position on Cancer Effects

CRE believes that there is no credible scientific evidence that atrazine poses a cancer risk to human beings.

Non-Cancer Effects

EPA's Human Health Risk Assessment concluded that atrazine poses no acute toxicity risks of concern.

Based on rat tests, EPA's human health risk assessment identified effects on the hypothalamic-pituitary function as the short-term, intermediate-term and chronic effect of concern. According to EPA, atrazine:

  • decreases the hypothalamic gonadotrophin releasing homone ("GnRH") release in rats;
  • diminishes norepinephine in the rat hypothalamus;
  • increases dopamine levels in rats which can result in a diminished pituitary secretion of prolactin; and attenuates the lutenizing hormone ("LH") surge

EPA believes that these effects on the hypothalamic-pituitary function "can potentially broadly affect an individual's functional status and lead to a variety of health consequences." Human Health Risk Assessment, p. 16. Based on rat tests, EPA selected attenuation of LH surge as the basis for the intermediate-term and chronic risk assessment for all human populations because EPA believes it is a biomarker of alterations to the hypothalamic/pituitary/gonadal axis.

EPA concluded that, nationally, approximately 30 community water systems out of 21,000 community waters systems in the 21 heaviest use atrazine states — and eight rural wells out of 1505 rural wells tested — had atrazine levels that exceed EPA's levels of concern for infants. EPA also concluded that several residential atrazine use exposure scenarios exceed EPA's short-term levels of concern for adults and children.

Syngenta believes that EPA's selection of 12.5 ppb (total chloro-triazines) as a 90-day rolling maximum as a level of concern for non-cancer human health effects is inappropriate. The 12 ppb level is based on a toxicological endpoint (leutinizing hormone suppression) that has no relevance to infants. The hypothalamic-pituitary (LH) axis is not active in infants and children because it is suppressed by the brain. The LH endpoint thus cannot validly be used as an indicator of levels of toxicological concern to infants or children.

Second, because atrazine's well-defined mode of action is not operative in infants and children, the FQPA additional 10x margin of safety factor should not be applied.Furthermore, studies show that the young are less sensitive to atrazine than adults. Studies conducted on pre-pubescent rats (when the LH-based mode of action becomes relevant) have shown NOELs that are 3 times higher than in adult rats. These results clearly demonstrate that the adult is more sensitive to atrazine than younger animals.

Third, the 1.8 mg/kg-day adult-based NOEL is quite protective of the types of shorter-term or intermittent exposures that may result from atrazine use. This NOEL represents long-term, daily exposure to adult rats for a quarter of their lifetime. It is, therefore, fully protective relative to shorter-term or intermittent exposures possible to humans. In addition, concerns about exposure to the young can be addressed by using endpoints that are relevant to the young. These endpoints, as previously mentioned, are approximately 3-fold higher than in the adult and thus are adequately covered by the 1.8 mg/kg-day adult-based NOEL.

In summary, Syngenta's position is that the atrazine-relevant mode of action is not operative in the young (obviating the need for the FQPA 10x factor) and the adult NOEL is based on a much longer duration of exposure than is likely for humans. For these reasons, an exceedance of the 12.5 ppb level is a prudent trigger for mitigation action only. It is not an indicator of likely adverse effects, and, therefore, exceedance of this early warning trigger does not warrant product cancellation in a watershed. Because of the multiple layers of conservatism in the risk assessment, there is already a "reasonable certainty of no harm" from atrazine exposures.

CRE's Position on Non-Cancer Effects

CRE concurs with Syngenta's position.

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