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Description of key information

A GLP, dietary, combined chronic toxicity and carcinogenicity study in rats conducted according to OECD test guideline 453 reported a carcinogenicity NOEL for Ametryn technical of 75 ppm (equivalent to 3.8, 5.0, and 4.4 mg/kg bw/day for males, females, and combined sexes, respectively) (Krishnappa, 2002).
Supportive data from 3 other GLP-compliant carcinogenicity or combined carcinogenicity and chronic toxicity studies in mice and rats have not reported any carcinogenic effects following dietary administration of Ametryn technical. There were no inhalational or dermal carcinogenicity studies conducted.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion
Dose descriptor:
4.4 mg/kg bw/day

Justification for classification or non-classification

Additional information

The carcinogenicity of Ametryn technical was evaluated in a 2-year combined chronic toxicity and carcinogenicity study in rats (Krishnappa, 2002). This GLP study was conducted according to OECD test guideline 453. Ametryn technical was administered in the diet at nominal concentrations of 0, 75, 280, or 1000 ppm to Wistar rats for 2 years (50 rats/sex/group). A subset of 10 (controls) or 20 (high-dose) animals/sex/group was sacrificed halfway through the study for analysis.  Histopathologic evaluations were conducted in control and high-dose animals, and in all pre-terminal decedents and moribund sacrificed animals.  There were no differences in survival reported. There were no treatment-related clinical signs observed.  Decreased growth and food consumption were noted for males and females in the 1000 ppm group, and early in the study for female rats of the 250 ppm group. Mild anaemia was reported in high dose females (as characterized by decreased RBC counts, haemoglobin concentration, and haematocrit levels, with increased MCH and MCHC values). There were no haematological changes in males. Increased total bilirubin, serum phosphorus, and chloride levels were observed in 1000 ppm males and females. Increased alkaline phosphatase and gamma glutamyl transpeptidase values were reported in high-dose females. There were no changes in urinalysis parameters observed. There were no treatment-related organ weight or gross pathology findings observed. Histopathological analysis did not reveal any treatment-related non-neoplastic or neoplastic changes. A higher number of neoplasms in the high-dose preterminal and moribund sacrificed animals were considered coincidental due to lack of significance in the dead and moribund animals (all fates) and because there was no significant increase in any particular tumour.

Based on these results, a NOEL of 75 ppm was identified for ametryn technical. This is equivalent to 3.8, 5.0, and 4.4 mg/kg bw/day for males, females, and combined sexes, respectively.

Supportive information on the carcinogenicity of Ametryn technical was provided by 3 additional GLP-compliant studies, involving dietary administration of Ametryn technical. These studies were conducted in mice or rats and were compliant with or similar to OECD test guidelines 451 or 453. Reported NOELs for 2 of these studies were 100 ppm (in mice) and 50 ppm (in rats). A third study did not identify a NOEL due to lack of adverse effects observed at dose concentrations up to 2000 ppm (in rats). There were no carcinogenic effects reported in any of these supportive studies.