Carcinogenicity atrazine

Atrazine was not carcinogenic to mice or Fischer rats after oral administration in the diet. An increase incidence of mammary tumors has been found in female Sprague-Dawley females treated similarly. The lARC has determined that the mammary tumors associated with atrazine exposure involve a mechanism that is non-DNA-reactive and hormonally mediated. They further stated that this mechanism is not relevant to humans. The lARC concluded that there was sufficient evidence for the carcinogenicity of atrazine in experimental animals and inadequate evidence of carcinogenicity in humans. ... 

It is possible to use this OH° concentration to predict k for the oxidation of other compounds under the same conditions. Von Gunten et al. (1995) calculated the actual concentration of OH° using this general and easy way for the ozonation of surface water at neutral pH in a two-stage pilot plant. Atrazine was used as the model compound, ozone decay was assumed to be of first order and the reactors completely mixed. Based on this model they were able to precisely predict the formation of bromate (Br03 ) by oxidation of bromide (Br ) for a full-scale water treatment plant. Bromate is a disinfection byproduct (DBP) of the ozonation of bromide-containing waters, and of concern because of its carcinogenic effects in animal experiments (see also Chapter A 3). 

Both atrazine and metolachlor are classified as potential human carcinogens by the USEPA, which has established a maximum contaminant level in drinking water of 3000 ng/L [78]. The maximum concentrations of atrazine and metolachlor measured in the 1994-2000 Great Lakes survey were 1039 ng/L and 736 ng/L, respectively. The effects of long-term, low-level concentrations of atrazine and metolachlor on aquatic ecosystems are largely unknown [79]. The Canadian guidelines for the protection of aquatic fife and drinking water (Table 8) were not exceeded for either of these herbicides [80-83]. 

In 1996 the United Kingdom, which was selected to conduct the scientific review of atrazine for the European Union (EU), concluded It is expected that the use of atrazine, consistent with good plant protection practice, will not have any harmful effects on human or animal health or any unacceptable effects on the environment (UK Rapporteur Monograph, 1996). In 2000, the United Kingdom for the European Commission also concluded it is not appropriate to classify atrazine as a carcinogen (UK Rapporteur Monograph, 2000). 

In 2001, the French Toxicity Research Commission on Pesticide Products cited conclusions by IARC, USEPA, and EU that atrazine is not carcinogenic to humans (French Republic Ministry of Agriculture, 2001). The Commission further stated, Considering all these factors, the concentration of the triazines in water, even elevated levels identified in the field both in transitory and localized form, do not represent a public health risk. ... 

The United States After reviewing the scientific data on atrazine since initiation of the Special Review in 1994 and changes in pesticide regulations under the Food Quality Protection Act in 1996, the USEPA in 2000 convened a Scientific Advisory Panel (SAP) to provide scientific advice on the potential for atrazine to be a carcinogen. The SAP concluded that atrazine was not likely to be carcinogenic to humans. In 2000, USEPA published its determination that... 

USEPA (2000). Cancer Assessment Review Committee, Atrazine Evaluation of Carcinogenic Potential. December 13, 2000. HED Doc. No. 014431. 

Detailed studies on atrazine have shown that F-344 rats administered high doses of atrazine do not develop either an increased incidence or an early onset of mammary tumors (Wetzel et al, 1994 Thakur et al, 1998), unlike the findings noted in similarly treated female SD rats (Stevens et al, 1994 Wetzel et al, 1994 Hauswirth and Wetzel, 1998). Furthermore, when ovarian estrogen was eliminated from the female SD rats by surgical removal of the ovaries, no mammary tumors were found (Stevens et al, 1999). Likewise, atrazine is not carcinogenic in mice or male SD rats (Hauswirth and Wetzel, 1998). 

Reviews from the USEPA (2003a), the European Union (UK, 2000), the APVMA (2004), and IARC (1999) concluded that the mechanism underlying the occurrence of atrazine-induced mammary tumors in female SD rats is not relevant to humans. Atrazine is classified as not likely to be a human carcinogen by the USEPA. 

The International Agency for Research on Cancer (IARC, 1999) concluded there is strong evidence that the mechanism by which atrazine increases the incidence of mammary gland tumors in SD rats is not relevant to humans and that atrazine is not classifiable as to its carcinogenicity to humans. 

After review by its Scientific Advisory Panel (SAP), the USEPA (2000, 2002, 2003a) has concurred with IARC (1999) that the mammary tumor response observed in the SD female rat is not considered relevant to humans and USEPA classified atrazine as not likely to be a human carcinogen. 

Therefore, when it became clearly understood that atrazine is neither estrogenic nor a genotoxic, direct-acting carcinogen - and that the atrazine-associated tumor responses appeared only in female SD rats, a strain with a high, normally occurring incidence of mammary tumors - it became important to study the effect of high doses of atrazine on the SD animal model s own endocrine system and hormonal milieu. 

Toxicity The acute oral toxicity of atrazine in rats is 2,850 mg/kg, and the acute dermal toxicity in rabbits is 7,550 mg/kg. The acute inhalation LC50 (1 hour) in rats is greater 167 mg/L. Atrazine did not cause any primary irritation in rabbits, although it caused eye irritation in rabbits.17 A carcinogenicity study of mice exposed to atrazine through diet (82 ppm) for 18 months is sketchy and requires more confirmatory data.23,24... 

At the time this analysis was carried out, there was some debate as to whether atrazine and simazine should be considered to be carcinogens. It has been concluded that since the cancer rate was increased at only one site in one strain of rat, but not in other rat strains or mice, that they are not carcinogens. However, this analysis shows how a positive carcinogen could be handled. The MOEs reported herein are based on a lower bound on the lifetime average daily intake that produced an increase of 0.10 in the cancer probability in the most sensitive tissue in the most sensitive animal species and sex. 

The carcinogenic effect of high doses of atrazine noted in female Sprague-Dawley rats is a strain-, sex-, and tissue-specific response that may not have biological relevance to humans due to the differences in the endocrine control of reproductive senescence. 

We tried to obtain a herbicide binder from a tetrapeptide library. The herbicides diuron (DCMU) [3-(3,4-dichlorophenyl)-l, 1-dimethylurea] and atrazine (2-chloro-4-(ethylamino)-6-(isopropylamino)-s-triazine) are widely used for crop protection (Fig. 8.4). However, due to their widespread use, they contribute greatly to water pollution on a worldwide scale.24,25 Many risk characterizations or epidemiological studies on triazine herbicides (i.e., atrazine, simazine, cyanazine) have been reported including the clastogenic potentials of atrazine and simazine to Chinese hamster ovary cells26 or their carcinogenicity.27,28 The standard level of atrazine in... 

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