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Key value for chemical safety assessment

Effects on fertility

Description of key information
Reproductive toxicity
One-generation
The reproductive and developmental NOEL was 250 ppm in rats (OECD TG 415)
Additional information

Potential effects of the test material on fertility were evaluated in a one generation reproduction study in rats. There were no treatment-related effects on estrus cycling at any dietary concentration up to and including 1500 ppm as determined by number of estrus stages during the evaluation period or mean cycle length. There were no treatment-related effects on sperm motility, morphology, epididymal sperm count or concentration, testicular sperm count and concentration at any dietary level up to and including 1500 ppm.

Additionally, in a 4-week repeated-exposure inhalation toxicity study testicular weights and testicular as well as uterine histopathology was not altered following exposure to the test material. In 4-week repeated-exposure dermal toxicity study testicular weight and histopathology was not altered following exposure to the test material.


Short description of key information:
Reproductive toxicity
One-generation
The reproductive and developmental NOEL was 250 ppm in rats (OECD TG 415)
BMDL10 511 ppm

Effects on developmental toxicity

Description of key information
Developmental toxicity/teratogenicity
The NOAEL for teratogenicity 45 mg/kg in rats (OECD TG 414)
Effect on developmental toxicity: via dermal route
Dose descriptor:
NOAEL
45 mg/kg bw/day
Additional information

Presumed pregnant Crl:CD®(SD)IGS BR VAF/Plus® rats were exposed to solutions of the test substance in Neutral Oil 100 N administered percutaneously once daily on days 6 through 20 of presumed gestation (DGs 6 through 20) at dosages of 0 (Vehicle), 5, 15 and 45 mg/kg/day. No fetal gross external, soft tissue or skeletal alterations (malformations or variations) were caused by dosages of the test substance as high as 45 mg/kg/day. The maternal no-observed-adverse-effect-level is 5 mg/kg/day. Adverse clinical observations, skin reactions and reductions in body weights and feed consumption were observed in the 15 and/or 45 mg/kg/day dose groups. An increase in the number of rats sacrificed for humane reasons was observed in the 45mg/kg/day dose group. No developmental effects were seen at any doses that were related to treatment with test material. The developmental NOEL is 45 mg/kg/day.

Toxicity to reproduction: other studies

Additional information

This study was performed to investigate the effects of the test material on growth, development and reproductive performance in male and female rats through one generation. The test material was administered in the diet at concentrations of 0, 250, 750 or 1500 ppm. These dietary concentrations resulted in consumed doses of 0, 19.1, 55.6, and 107.3 mg/kg/day respectively in males during premating and 21.0, 62.8, and 124.1 mg/kg/day respectively in females during premating. Continuous exposure of rats to test material in the diet through one generation had a No Observed Effect Level (NOEL) for parental animal toxicity of 250 ppm [19.1 mg/kg/day in males; 21.0 mg/kg/day in females]. The reproductive and developmental NOEL was 250 ppm due to decreased pup body weights at both 750 and 1500 ppm and delayed sexual maturation in females at 750 ppm and in both sexes at 1500 ppm. Detailed evaluation of the study data revealed a clear weight of evidence to support the conclusion that the delays in puberty onset by the test material are due to decrements in pup body weight secondary to maternal toxicity.

Justification for classification or non-classification

No developmental effects were seen at any doses that were related to treatment with the test material in a percutaneous pre-natal developmental study.

The test material is not classified as a reproductive toxicant. Detailed evaluation of the study data revealed a clear weight of evidence to support the conclusion that delays in puberty onset by the test material are due to decrements in pup body weight secondary to maternal toxicity and therefore do not warrant reproductive or developmental classification.