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

Toxicity to reproduction

Administrative data

Endpoint:

three-generation reproductive toxicity

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

March 1981- March 1983

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

This study was conducted with a method equivalent to the OECD 416 (2001): OPPTS 870.3800 (1998): 2004/73/EC B.35 (2004) Guidelines and following the principlesand 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.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1984

Report date:

1984

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 416 (Two-Generation Reproduction Toxicity Study)

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

EPA OPPTS 870.3800 (Reproduction and Fertility Effects)

Test guideline 3

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method B.35 (Two-Generation Reproduction Toxicity Test)

Principles of method if other than guideline:

The following deviations from the current guidelines were noted: Oestrus cycle length and normality were not evaluated by vaginal smears prior to mating. Daily dosing of the parental animals began when they were approx 4 weeks of age but continued for at least 12 weeks prior to the mating period. The animals were only observed once daily for morbidity and mortality. Food consumption was not measured during gestation. No organ weights were recorded. Testes and epididymides were not used for enumeration of homogenisation-resistant spermatids and cauda epididymides sperm reserves. Sperm motility and sperm morphology were not evaluated. Live pups were counted and litters weighed (pup weights) on the morning after birth and on days 4 and 7 and 21 of lactation and at termination. Timing of sexual maturation was not recorded. Anogenital distance was not recorded. Functional investigations of offspring were not assessed. At the time of necropsy, a vaginal smear was not taken to determine the stage of the oestrus cycle. The uteri of all primiparous females were not examined for the presence and number of implantation sites. A quantitative evaluation of primordial follicles was not conducted for F1 females. A copy of the study protocol is not included in the report. None of these deviations from the current regulatory guideline are considered to compromise the scientific validity of the study.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

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

EC Number:

932-389-6

Molecular formula:

C23H19ClF3NO3

IUPAC Name:

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

Results and discussion

Overall reproductive toxicity

Reproductive effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

The study is considered to be reliable with restrictions. The results are sufficiently detailed and unambiguous as to be adequate for risk assessment, classification and labeling.

Executive summary:

In a three-generation reproduction study, cyhalothrin was administered to Alpk/AP, (Wistar derived) rats in the diet at dose levels of 0, 10, 30 or 100 ppm (males: 0, 0.5-0.6, 1.5-1.7, or 5.2-5.7 mg/kg bw/day respectively; females: 0, 0.5-0.7, 1.5-1.9 or 5.2-6.1 mg/kg bw/day respectively). The purpose of this study was to assess the effects of the continuous feeding of diets containing cyhalothrin on the reproductive performance of three generations of the rat. 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 diets containing 0, 10, 30 or l00 ppm cyhalothrin. 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. The effect persisted through the lactation period. Though the effect is minor it 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 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.