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

Endpoint summary

Description of key information

NOAEL=3 mg/kgbw/day, 28 day and 90 day studies in the rat, Lindsay
NOAEL=2.5 mg/kgbw/day, 26 week study in the dog, Chesterman

Additional information

The toxicity of cyhalothrin has been studied in 28 day and 90 day studies in the rat and in a 26 week study in the dog. 

The reversibility of the liver changes was investigated in a 28-day study with cyhalothrin at a dietary concentration of 250 ppm as an aid to establishing their significance. A decrease in bodyweight gain was seen in the 250 ppm cyhalothrin group, which persisted during the 28 day recovery period. Proliferation of the hepatic smooth endoplasmic reticulum and elevated hepatic aminopyrine-N-demethylase activity were also seen in the treatment group. These effects had reversed 7 days after the cessation of treatment with cyhalothrin and were considered to be physiological adaptive changes rather than a toxicological effect.

Administration of 250 ppm cyhalothrin in diet produced reversible and adaptive changes in the liver, characterised by SER proliferation and increased APDM activity. This level of cyhalothrin also produced a decrease in bodyweight gain which was still apparent 28 days after the cessation of treatment.

In two subchronic toxicity studies in rats, groups of 20 male and 20 female rats were fed cyhalothrin at dose levels of 0, 10, 50 or 250 ppm in diet for 90 consecutive days.

There were no mortalities or treatment-related clinical signs, including no evidence of neurological effects. There were no treatment-related ophthalmological changes. Decreased bodyweight gain accompanied by poor food consumption was evident in males fed 250 ppm cyhalothrin. There were no treatment-related or toxicologically significant changes in haematological, clinical chemistry or urinalysis parameters. At 250 ppm in both males and females and at 50 ppm in males, cyhalothrin induced an adaptive response in the liver, characterised by increased liver weight accompanied by increased activity of hepatic aminopyrine-N-demethylase (APDM). There were no other toxicologically significant, treatment-related effects on organ weights, macroscopic or microscopic findings. A no observed adverse effect level (NOAEL) of 50 ppm for cyhalothrin was established on the basis of toxicity in the form of significantly reduced bodyweight at 250 ppm (males). The NOAEL of 50 ppm equates to an achieved dose of approximately 3 mg/kg bw/day.

Oral subchronic studies in beagle dogs dosed by capsule with cyhalothrin produced neurological effects typical of pyrethroid toxicity after dosing including unsteadiness, collapse, marked incoordination, muscle tremors and convulsions at the highest dose levels. Vomiting or regurgitation was sometimes observed at high doses. These findings were transient and animals had usually recovered prior to dosing the following day. Other signs of toxicity were characterised by some instances of reduced bodyweight and/or reduced food consumption at high doses. The passage of fluid faeces was a characteristic observation in all studies and the incidence was generally dose related. However, this finding was not accompanied by any gastro-intestinal lesions and did not adversely affect the health of animals. It was attributed to an irritant/pharmacological effect of the compound which was exacerbated when given as a bolus dose on an empty stomach and was considered not to be of toxicological importance. There were no remarkable findings among clinical pathology parameters and there was no evidence of treatment related changes in organ weights and macroscopic or microscopic pathology.

When administered orally to beagle dogs for 26 weeks, 10.0 mg/kg/day of cyhalothrin in corn oil produced definite toxicological effects. A dose of 2.5 mg/kg/day of cyhalothrin was considered to be a NOAEL.

 

Justification for classification or non-classification

The 28-day oral toxicity study in the rats was conducted according to the principles and practices of Good Laboratory Practice. A Quality Assurance statement is included in the report. This was an investigative study therefore not required to comply with any current regulatory guideline.

The 90 day study in the rat was conducted using a method equivalent to the OECD 408 (1998), OPPTS 870.3100 (1998), 2001/59/EC B.26 (2001) 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.

The 26 week study in the dog was conducted using a method equivalent to the OECD 409 (1998): OPPTS 870.3150 (1998): 2001/59/EC B.27 (2001) 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.

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

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