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

Key value for chemical safety assessment

Effects on fertility

Additional information

Short description of key information:
NOEL reproductive toxicity=1.5-1.9 mg/kg/day, rat, method equivalent to the OECD 416 (2001), Milburn
NOEL maternity toxicity=10 mg/kg/day, rat, method equivalent to the OECD 414 (2001), Killick
NOEL developmental toxicity=15 mg/kg/day, rat, method equivalent to the OECD 414 (2001), Killick
NOEL maternity toxicity=10 mg/kg/day, rabbit, method equivalent to the OECD 414 (2001), Killick
NOEL developmental toxicity=10 mg/kg/day, rabbit, method equivalent to the OECD 414 (2001), Killick

Effects on developmental toxicity

Description of key information

The reproductive toxicity of cyhalothrin has been examined in developmental toxicity (teratology) studies in the rat and rabbit.

Toxicity to reproduction: other studies

Additional information

The reproductive toxicity of cyhalothrin has been examined in a three generation reproduction study in the rat and in developmental toxicity (teratology) studies in the rat and rabbit.

In a three-generation reproduction study, cyhalothrin was administered to rats in the diet at dose levels of 0, 10, 30 or 100 ppm (Milburn et al, 1984). The fertility of each generation of parental animals and the clinical condition, survival and subsequent growth of their offspring was determined. Groups of 15 male and 30 female (F₀Parents) weanling rats were fed their respective control or treated diets and after twelve weeks, animals were mated to produce the first (F₁A) litter and subsequently re-mated to produce a second (F₁B) litter. The breeding programme was repeated with F₁parents selected from the F₁B offspring and F₂parents selected from the F₂B offspring. Test diets were fed continuously through the study. There were minor reductions in bodyweight gain of parents from all generations receiving 100 ppm cyhalothrin. No effects of treatment were seen on indices of male and female fertility, gestation period, live born index or pup survival. There was a small reduction in mean total litter weight of the F₂and F₃generations from rats receiving 100 ppm cyhalothrin. This was attributable to minor decreases in litter size and a small reduction in weight gain of the pups. This minor effect persisted through the lactation period and may be treatment-related. No effect was seen in litters from rats receiving 30 ppm cyhalothrin. There was no evidence of gross or histopathological changes attributable to treatment. The NOEL for reproductive toxicity was concluded to be 30 ppm cyhalothrin (corresponding to a minimum dose rate in the range 1.5-1.9 mg/kg/day).

In a developmental toxicity study groups of 24 sexually mature mated female rats received cyhalothrin by gavage at dosages of 5, 10 or 15 mg/kg body weight daily for 10 consecutive days, from day 6 to 15 of gestation (Killick, 1981). A group of similar rats which received maize oil (the vehicle) over the same period served as the control group. The animals were killed on day 20 of gestation. There were no mortalities in the control or cyhalothrintreated groups. Two animals given 15 mg/kg/day cyhalothrin showed loss of limb co-ordination. Otherwise there were no changes in clinical condition attributable to treatment with cyhalothrin and no macroscopic changes were observed at necropsy. The initial effect of treatment with cyhalothrin on maternal body weight was dosage-related, with weight loss being observed in all groups, however the effects at 5 and 10 mg/kg/day were marginal and not of toxicological significance. An overall significant reduction of body weight gain and reduced food intake at 15 mg/kg/day was indicative of maternal toxicity. There was no effect of treatment with cyhalothrin on pregnancy incidence or on caesarean parameters at termination as assessed by the number, size, weight and sex of the foetuses and by pre and post-implantation losses. There was no effect of treatment with cyhalothrin on the incidence of major defects, minor external and visceral defects or minor skeletal defects and variants. The maternal toxicity NOAEL was 10 mg/kg/day and the developmental toxicity NOAEL was 15 mg/kg/day, the highest dose tested.

In a developmental toxicity study in rabbits,groups of sexually mature mated female New Zealand White rabbits received cyhalothrin by gavage at dosages of 3, 10 or 30 mg/kg body weight daily for 13 consecutive days from day 6 to 18 of gestation (Killick, 1981). A group of similar rabbits received maize oil (the vehicle) over the same period and served as the control group. The animals were killed on day 28 of gestation. Deaths occurred in all groups, including the control, the incidence being 1, 2, 6 and 2 in the control, 3, 10 and 30 mg/kg/day cyhalothrin treated groups respectively. None of the deaths however, was considered to be related to treatment with cyhalothrin. Amongst the surviving, there were no changes in clinical condition attributable to treatment with cyhalothrin and no macroscopic changes were observed at necropsy. Treatment with cyhalothrin at 30 mg/kg/day was associated with maternal weight loss, a slight reduction of body weight gain during the treatment period only and associated reduction in food intake. There was no apparent effect of treatment with cyhalothrin on pregnancy incidence or on gravid uterus weights. A marginal reduction in foetal weight at 30 mg/kg/day was not conclusively related to treatment with cyhalothrin but may indicate a marginal foetotoxic effect. Otherwise, there were no adverse effects of treatment with cyhalothrin on pre- and post-implantation losses, the number and sex of the foetuses, litter weight and foetal crown/rump length. Treatment with cyhalothrin did not adversely affect the incidence of major defects, minor external and visceral defects or minor skeletal defects and variants. The NOAEL for maternal and developmental toxicity was 10 mg/kg/day.

Justification for classification or non-classification

The Multigeneration Reproduction Study (rat) was performed under OECD 416 (2001): OPPTS 870.3800 (1998): 2004/73/EC B.35 (2004) guidelines with some deviations.This study was conducted according to the principles and practices of Good Laboratory Practice. A Quality Assurance statement is included in the report. The deviations from the current regulatory guideline are considered not to compromise the scientific validity of the studies.

The reproductive effects seen in rats receiving 100 ppm cyhalothrin were of a minor nature; 30 ppm cyhalothrin (corresponding to a minimum dose rate in the range 1.5-1.9 mg/kg/day) is established as a clear no-effect level.

 

The Prenatal Developmental Study (rat) was performed under OECD 414 (2001): OPPTS 870.3700 (1998): 2004/73/EC B.31 (2004) guidelines with some deviations.This study was conducted according to the principles and practices of Good Laboratory Practice. A Quality Assurance statement is included in the report.

The deviations from the current regulatory guideline are considered not to compromise the scientific validity of the studies.

Administration of cyhalothrin at 15 mg/kg/day by the oral route during days 6 to 15 of gestation elicited maternal toxicity. However, there was no effect of treatment at 5, 10 or 15 mg/kg/day on any aspect of foetal development. The maternal toxicity NOAEL is 10 mg/kg/day and the developmental toxicity NOAEL is > 15 mg/kg/day.

 

The Prenatal Developmental Study (rabbit) was performed under OECD 414 (2001): OPPTS 870.3700 (1998): 2004/73/EC B.31 (2004) guidelines with some deviations. This study was conducted according to the principles and practices of Good Laboratory Practice. A Quality Assurance statement is included in the report.

Administration of cyhalothrin at 30 mg/kg/day by the oral route during days 6 to 18 of gestation elicited maternal toxicity. A marginal reduction in foetal weight at 30 mg/kg/day was not conclusively related to treatment with cyhalothrin.

Administration of cyhalothrin at 3 or 10 mg/kg/day did not elicit maternal toxicity or affect any aspect of foetal development. The NOAEL for maternal and developmental toxicity is 10 mg/kg/day.

 

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.