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

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

November 1980 - December 1980

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 414 (2001): OPPTS 870.3700 (1998): 2004/73/EC B.31 (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:

1981

Report date:

1981

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

EPA OPPTS 870.3700 (Prenatal Developmental Toxicity Study)

Test guideline 3

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method B.31 (Prenatal Developmental Toxicity Study)

Principles of method if other than guideline:

The following deviations from current guidelines were noted:
The volume administered was 10 ml/kg in maize oil (the current guideline states that when corn oil is used as a vehicle, the volume should not exceed 0.4 ml/100 g bodyweight).
The test substance was not administered daily from pre-implantation (e.g. day 5 post mating) until the day prior to scheduled caesarean section.
Two-thirds of each litter (rather than half) were processed for skeletal examination and one-third for soft tissue examination.
These deviations from the current regulatory guideline are considered not 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

Results (fetuses)

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental 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:

Groups of 24 sexually mature mated female rats receivedcyhalothrin 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. Agroup 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.

Clinical condition, body weight, food intake, pregnancy incidence and the outcome of gestation were assessed.

There were no mortalities in the control or cyhalothrintreated groups.

Two animals given 15 mg/kg/day cyhalothrin showed loss of limb co-ordination. This change in behaviour, although of very low incidence in this study, has previously been attributed to treatment with cyhalothrin at higher dosages. Otherwise there were no changes in clinical condition attributableto 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. Treatment with cyhalothrin at 15 mg/kg/day was associated with an overall significant reduction of body weight gain. However, the rate of weight gain from day 7 was generally comparable with the control group. Only marginal reductions in body weight gain were recorded at 5 and 10 mg/kg/day cyhalothrin.

Treatment with cyhalothrin at 15 mg/kg/day was alsoassociated with reduced food intake throughout the study, thedifference from the controls being significant between days 6 and12 of gestation. At 5 and 10 mg/kg/day cyhalothrin, only slightreductions in food intake were apparent during the study.

There was no effect of treatment with cyhalothrin on pregnancy incidence.

There was no effect of treatment with cyhalothrin oncaesarean parameters on day 20 of pregnancy as assessed by the number, size, weight and sex of the foetuses and by pre and post-implantation losses. Further, gravid uterus weights were comparable in all groups.

There was no effect of treatment with cyhalothrin on theincidence of major defects, minor external and visceral defects orminor skeletal defects and variants.

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.