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Background Information on Cyanazine

Background Information on Cyanazine

On the Announcement of the Phase-out of the Herbicide Cyanazine
Wednesday, August 2, 1995

Cyanazine Use

Cyanazine is sold by DuPont Chemical as Bladex, and has been in use since 1971. It is the fourth most widely used synthetic chemical pesticide in U.S. agriculture. An estimated 30-35 million pounds were applied in 1993 (Aspeline 1994), primarily on corn fields to control grasses and broad leaf weeds. Based on information reported by the EPA, the USDA, and others, the use of cyanazine appears to be increasing.

 

Cyanazine Contamination of Drinking Water

Cyanazine is relatively persistent in the environment, and under certain conditions will remain at significant levels in surface water for over one year. Cyanazine has been found in groundwater in 15 states at concentrations up to 29 ppb, and as a surface water contaminant in 30 states (EPA 1992, STORET 1994). The Environmental Working Group has identified cyanazine as a drinking water contaminant throughout the Mississippi River basin.

 

Health Hazards

Cyanazine is essentially atrazine with cyanide attached to it. It is a teratogen (causes birth defects) and a mutagen (causes genetic mutations) as well as a carcinogen. Overall, cyanazine is the most toxic triazine herbicide, and may be the most toxic of all herbicides found in drinking water.

Birth Defects. Cyanazine causes a number of different birth defects in several species of animals including serious abnormalities of the eye, the diaphragm, and the brain, as well as cleft palate, and alterations in skeletal development (Rinde 1991). Three separate investigations of cyanazine in two species, the rabbit and rat, reported a dose-related increase in anophthalmia and/or microphthalmia (animals born without eyes or with abnormally small eyes). The effect occurred at doses from 4 mg/kg in the rabbit to 25 and 75 mg/kg in the rat. Many of these same animals exhibited other effects described below (Bui 1985, Rinde 1991).

Diaphragm related malformations, including diaphragmatic hernia and an "incomplete fusion of the diaphragm central area tendon with raised area of the liver," were found in two studies of F-344 rats fed cyanazine (Bui 1985 pg. 3). In the first study diaphragm problems were found at all doses (1, 2.5, 10, and 25 mg/kg), including levels not overtly toxic to the mother. In the second study, using the same strain of rat, the doses were 5, 25, and 75 mg/kg.

Alterations in skeletal ossification sites were found at all doses tested. Defects in the diaphragm were significantly increased at the 25 mg/kg doses level, and a host of defects including anophthalmia/microphthalmia, dilated brain ventricles, cleft palate, and diaphragm- related malformations were present at 75 mg/kg. Cyanazine also causes dilated brain ventricles in the rabbit and the rat, and domed cranium in the rabbit (Bui 1985, Rinde 1991).

Mutations. Cyanazine is also mutagenic in several assays. It induces forward mutation in a dose-related manner in repeat assays with and without metabolic activation in a mouse lymphoma cell gene mutation assay. Cyanazine also caused unscheduled DNA synthesis in repeat assays in rat hepatocytes. The herbicide did not produce mutations in hamster ovary cells or in human lymphocytes.

Overall this genotoxicity presents serious concern and adds to the evidence of carcinogenicity. According to the final internal EPA peer review of cyanazine, "This genotoxic activity provides support for a (sic) carcinogenicity and concern for heritable effects." (Dykstra 1991 pg. 15). The peer review further noted that cyanazine's genotoxicity reinforces concerns about its overall toxicity and is consistent with the fact that cyanazine induces a carcinogenic response at lower doses than the other triazines (Dykstra 1991).

Cancer. Cyanazine is also a potent carcinogen that appears to act via the same hormonal mechanism as atrazine and simazine. With cyanazine, however, tumors appear at lower doses and with higher rates of malignancy than its chemical cousins. Cyanazine in the diet at 5, 25, and 50 mg/kg caused a statistically significant increase total malignant mammary tumors, and a statistically significant positive trend for these tumors in female rats. Three types of malignancies were observed (adenocarcinoma, carcinosarcoma, and fibrosarcoma), although the vast majority of the malignant tumors were adenocarcinomas. Cyanazine has the highest Q* (quantitative potency rating) of any pesticide in widespread use today 1.0 (mg/kg/day)-1 (Engler 1994). Consequently, the Office of Pesticide Programs regulates cyanazine as a carcinogen in food, using methods that provide greater public health protection than safety factor methods used to protect against the birth defects described above (Dykstra 1991, Ghali 1985).

Results from two additional studies indicate an increase in several additional tumors in both male and female rats. The results of these studies were compromised, however, and the studies were deemed invalid by the EPA due to the small number of animals per dose group, the failure to expose the animals to the maximum tolerated dose, the limited number of tissues analyzed, discrepancies in reporting and histopathology, and other inconsistencies.

For example, according to EPA reviewers, the limited number of animals per dose group (24) in one study reduced the power of the study to validate possible compound related effects such as the increase in "adrenal pheocromocytoma in both sexes of rats, and for thyroid adenoma in males and pituitary tumors in females." (Ghali 1985, Taylor 1985).

Regulatory Actions On Cyanazine. Prior to the August 2 announcement of a voluntary phase-out of cyanazine, EPA had established a no observable adverse effects level (NOAEL) for developmental effects of 1 mg/kg. In the same memorandum that recommends this 1 mg/kg NOAEL, however, the agency notes that both diaphragm defects and adverse developmental effects occur at the 1 mg/kg body weight per day dose level in the F-344 rat (Bui 1985). This obvious contradiction was "resolved" when the agency dismissed these defects due to lack of historical control data for these specific malformations and the absence of these same defects at the 5 mg/kg dose in a repeat study (Bui 1985). A more accurate characterization of these collective developmental toxicology studies would be that they provide no evidence of a dose that is safe for a developing fetus.

As a result of health effects studies the EPA classified cyanazine as a developmental toxicant and teratogen. The agency now requires a warning statement to this effect on the labels of all agricultural herbicide formulations containing cyanazine.

As noted above, cyanazine is also a potent carcinogen that appears to act via the same hormonal mechanism as atrazine and simazine. The EPA Office of Ground Water and Drinking Water (OGDW) had long ignored the powerful evidence regarding the pesticide's carcinogenicity and had proposed weaker drinking water standards that do not regulate cyanazine as a carcinogen. In fact, OGDW has not yet even promulgated an enforceable drinking water standard for cyanazine. The current lifetime health advisory (LHA) of 1 ppb is not enforceable and is not based on cyanazine's cancer potency. Were OGDW to regulate cyanazine as a carcinogen, the maximum contaminant level in drinking water would be about 0.03 ppb, about 33 times lower than the current LHA of 1 ppb.

 

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