Reaction mass of (R)-cyano(3-phenoxyphenyl)methyl rel-(1R,3R)-3-((1Z)-2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethylcyclopropanecarboxylate and (R)-cyano(3-phenoxyphenyl)methyl rel-(1S,3S)-3-((1Z)-2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethylcyclopropanecarboxylate

Carcinogenicity

Description of key information

NOAEL = 50 ppm,  1.7 mg cyhalothrin/kg/day for male rats and 1.9 mg/kg/day for female rats.
NOAEL = 20 ppm,  1.81 mg/kg/day in the males and 2.03 mg/kg/day in the females mice. 

Justification for classification or non-classification

The two year feeding study in rats was conducted with a method equivalent to the OECD 453 (1981), OPPTS 870.4300 (1998), 87/302/EEC B.33 (1988) Guidelines and following the principles and practices of Good laboratory Practice. A Quality Assurance statement is included in the report.

None of the deviations from the current regulatory guideline are considered to compromise the scientific validity of the study.

There were no neurological effects at any dose level of cyhalothrin in this study. There was no evidence for a carcinogenic effect of cyhalothrin.

The carcinogenicity study on mice was conducted with a method equivalent to the OECD 451 (1981): OPPTS 870.4200 (1998): 87/302/EEC B.32 (1988) Guidelines and following the principles and practices of Good laboratory Practice. A Quality Assurance statement is included in the report.

None of the deviations from the current regulatory guideline are considered to compromise the scientific validity of the study.

Based on the results, it is concluded that cyhalothrin is not carcinogenic in the mouse.

The studies are considered adequate and reliable for the purposes of classification and labeling.

The results do not lead to classification according to Directive 67/548/EEC or according to Regulation 1272/2008.

Additional information

In a 2-year combined toxicity and carcinogenicity study groups of 72 male and 72 female rats were fed diets containing 0, 10, 50 or 250 ppm cyhalothrin from approximately 5 weeks of age. Ten rats of each sex from each group were designated for interim sacrifice during week 53, the remainder continued on the study for up to 104/105 weeks when all surviving rats were terminated. There was no treatment related effect on survival and there were no clinical signs attributed to cyhalothrin. Decreased bodyweight gain, accompanied by a small decrease in food consumption, was evident in rats of both sexes fed 250 ppm cyhalothrin. This was accompanied by minor changes in blood biochemistry. Increased liver weight was seen in rats of both sexes fed cyhalothrin at 250 ppm at the interim sacrifice (consistent with the 90-day study) but this was not evident at termination. There was no histological evidence for a chronic toxic effect due to cyhalothrin and there was no treatment related effect on the tumour profile or tumour incidence. An unusual incidence of palatine fistulation and marked rhinitis developed late in the study, the first instance being recorded at 64 weeks. The lesions seemed to be caused by long painted fibres of cereal origin in the food whose presence was a consequence of a change in diet formulation during weeks 46-48 but the incidence was unrelated to treatment with cyhalothrin. Cyhalothrin was concluded to be non carcinogenic and the NOAEL for toxicity was 50 ppm cyhalothrin, corresponding to a minimum dose rate of approximately 1.7 mg cyhalothrin/kg/day for male rats and 1.9 mg/kg/day for female rats.

In a carcinogenicity study, groups of 64 male and 64 female mice were fed diets containing 0, 20, 100 or 500 ppm of cyhalothrin from approximately 5 weeks of age. Twelve mice of each sex from each group were designated for interim sacrifice after 52 weeks of treatment (satellite group). The remainder (main group) continued on the study for up to 104 weeks when all surviving rats were killed. There were no significant effects on survival and the only clinical findings considered to be related to treatment were an increased incidence of pilo-erection and hunched posture noted for mice receiving 500 ppm and male mice receiving 100 ppm. Other findings that showed a slightly higher incidence among treated males included fighting, emaciation, pallor and hyperactivity. Lower bodyweight gain noted for male mice receiving 500 ppm cyhalothrin in comparison to the controls was indicative of toxicity. Over the first 24 weeks of treatment lower efficiency of food utilisation was recorded for male mice receiving 500 ppm cyhalothrin. Clinical pathology parameters were largely unremarkable and there was no evidence of significant toxicity. At necropsy, a higher incidence of subcutaneous masses and swellings was noted for female mice receiving 100 or 500 ppm cyhalothrin. There were no effects on organ weight related to treatment with cyhalothrin. There were no non-neoplastic pathological changes indicative of toxicity. A slightly higher incidence of mammary adenocarcinomas was noted for female mice receiving 100 or 500 ppm cyhalothrin in comparison with the control group mice. However, the incidence showed no dose relationship and was within or close to the historic control range. Mammary adenocarcinoma is a common tumour of variable incidence in this particular strain of mouse (CD-1). Overall, it was concluded that the incidence of mammary adenocarcinomas was not treatment related and that cyhalothrin was not carcinogenic in the mouse. The NOAEL for toxicity was established at 20 ppm, equivalent to a mean calculated daily intake of 1.81 mg/kg/day in the males and 2.03 mg/kg/day in the females.