3,5,5-trimethylcyclohex-3-en-1-one

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Additional information

In a limited one generation study, 10 male and 10 female Wistar rats were exposed to 2872 mg/m3 (500 ppm) isophorone in air (Dutertre-Catella, 1976). After three months of exposure, 5 exposed males each were mated with 5 control and 5 exposed females, 5 control males each were mated with 5 control and 5 exposed females. Exposure of females continued throughout gestation and they were allowed to deliver. Treatment with isophorone did not influence pregnancy rates and litter sizes nor were there any abnormalities observed in the pups.

The histological examinations of the reproductive organs of male and female mice and rats (mammary gland, seminal vesicle, prostate/testis or ovary/uterus) treated orally with up to 1000 mg isophorone/kg bw for 13 weeks did not reveal any adverse effects after macroscopic and microscopic examination (NTP,1986). In a 90 days study with male and female beagle dogs (4 animals/dose/sex were administered up to 150 mg isophorone per kg bw per day) no changes were reported either after histopathological examination of testes, prostate, seminal vesicles and ovary, uterus, mammary gland respectively (Rohm & Haas Co., 1972a).

 

There is no evidence indicating that isophorone interferes adversely with the reproduction. No changes were observed in pregnancy rates, litter sizes, pups abnormalities or in histopathological examinations of the reproduction organs after long-term studies.

Short description of key information:
There is no evidence indicating that isophorone interferes adversely with the reproduction. No changes were observed in pregnancy rates, litter sizes, pups abnormalities or in histopathological examinations of the reproduction organs after long-term studies.

Effects on developmental toxicity

Description of key information

In an inhalation teratogenicity study, the NOAEL for maternal toxicity was 289 mg/m³ (based on a reduction in body weight gain of less than 7%).
Isophorone was neither embryotoxic nor teratogenic up to the highest test concentration of 664 mg/m³ isophorone.

Additional information

Pregnant Fischer 344 rats and CD-1 mice were exposed on days 6 through 15 of gestation to isophorone concentrations of 144, 289, or 664 mg/m³ (22 animals per dose level). There was a significant reduction in food consumption in rats of the highest dose group. Body weight was reduced in rats (gestation day 12: -6.1%; gestation day 15: -6.8%) and mice (gestation day 18, corrected for uterine weight: -5.6%) of the highest dose group. In rats, a dose related increase in alopecia was observed, as well as a discoloration of the cervical and anogenital region. In mice, this effect was observed only in one animal of the high dose group. Adverse effects on the fetuses were not observed (Exxon,1984).

 

In inhalation teratogenicity studies with rats and mice, the NOAELs for maternal toxicity were 289 mg/m³ (based on <7% reductions in body weight gains). Isophorone was neither embryotoxic nor teratogenic up to the highest test concentration of 664 mg/m³ isophorone.

Justification for classification or non-classification

Based on the available reproduction toxicity studies, Isophorone does not need to be classified for reproduction toxicity according to Directive 67/548/EEC and according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.