Dimethylcyclohex-3-ene-1-carbaldehyde

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

OECD TG 421 NOAEL ≥ 500 mg/kg bw/day

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

For reproduction toxicity there is one oral study available, conducted according to OECD guideline 421 in compliance with GLP, containing adequate information for the endpoint.

Additional information

A reproduction/ developmental toxicity screening was performed according to OECD TG 421 and GLP. The substance was administered orally (gavage) to male and female Wistar Han IGS rats at dose levels of 50, 150 and 500 mg/kg bw/day (12 rats/sex/dose level). Concurrent controls (12 rats/sex) were performed with the vehicle (corn oil). Parental animals were exposed 2 weeks prior mating and during mating. Male rats and non-mated female rats were exposed until sacrifice (study day 30). Mated females were dosed from the start of the gestation period (the finding of a sperm positive vaginal smear was considered gestation day 0) up to delivery of the pups. During the lactation period, females were dosed up to sacrifice, after overnight fasting, on day 14 of lactation. The test substance was considered to be homogeneously distributed and to be stable in the gavage liquids under the experimental conditions. Although the concentration of the test substance of the mid-dose groups of the gavage liquids prepared was 14% lower than intended, in general, the concentration of the test substance was close to intended (90-110% of the intended concentration).

Repeated dose effects, clinical signs: For the male and female animals, there were no mortalities observed and no treatment related effects on macroscopic parameters and body weight were observed. In addition, no treatment related changes in estrus cyclicity, fertility and reproductive performance in P0 was observed. Although food consumption was affected in the post-mating period of the male animals in mid- and high dose groups and in pregnant females in the high dose group, this was not considered as an adverse effect of the treatment. In male animals of the high-dose group, the absolute- (+13.6%) and relative (+16.8%) liver weights and the relative kidney weight (+8.0%) were statistically significantly increased as compared to the control animals. Microscopic evaluation revealed a treatment-related increase of accumulation of hyaline droplets in tubular epithelial cells in the outer cortex of the kidneys, accompanied by degenerative changes of these cells in 6/12 high dose males in most cases the hyaline droplets were also present in the lumen of the tubules. Immunohistochemically staining with a monoclonal antibody against alpha 2u revealed that there was insufficient evidence to identify the hyaline droplets as alpha 2 urinary microglobulins. In female animals of the mid- and high-dose groups, the absolute (+9.9% and +24.7%, respectively) and relative (+9.0% and +24.2%, respectively) weights of the liver were statistically significantly increased as compared to the control group. No toxicological adverse effects on T4 and TSH hormones were observed in male and female parental animals.

Fertility: No treatment related changes in estrus cyclicity, fertility and reproductive performance in P0 was observed. Minor food consumption effects were observed in the post-mating period of the male animals in mid- and high dose groups and in pregnant females in the high dose group, but this was not considered as an adverse effect of the treatment.

Developmental toxicity: In the pups, no treatment related effects were observed in observational studies, body weight, anogenital distance, nipple retention and thyroid weight. No effects were observed during macroscopic observations in both still born/ found-dead pups and after sacrifice (post-natal day 13). Microscopic evaluation of the thyroid gland did not reveal treatment related histopathological changes. No toxicological adverse effects on T4 and TSH hormones were in culled pups on postnatal day 4 and in male and female pups on postnatal day 13. 

In conclusion, systemic effects were observed in the high dose group (500 mg/kg bw/day). A NOAEL of 150 mg/kg bw/ day was therefore derived based on microscopic effects observed in the kidneys (male), which upon staining were not confirmed to be alpha hydrocarbon nephropathy. No adverse effects were observed on fertility parameters, reproductive performance and developmental parameters up to the highest dose tested. Therefore, the NOAEL for reproduction and developmental toxicity is ≥ 500 mg/kg bw/day.

Effects on developmental toxicity

Description of key information

OECD TG 421: NOAEL ≥ 500 mg/kg bw/day

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

For developmental toxicity there is one oral study available, conducted according to OECD guideline 421 in compliance with GLP, containing adequate information for the endpoint.

Additional information

See additional information in the Fertility section.

Justification for classification or non-classification

No adverse effects on reproduction parameters and on developmental parameters were observed in an OECD 421 reproduction/developmental toxicity screening study up to and including 500 mg/kg bw/day, the highest dose tested. Therefore, classification of the substance is not warranted according to EU CLP (EC No. 1272/2008 and its amendments).