Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Additional information

In the combined repeated dose reproduction/developmental screening test with dimethylmalonate in Wistar rats no treatment related changes in fertility index for males and females, gestation index, testes and epididymis weights were observed compared to the control. No treatment related histopathological changes of the sex organs or stages of spermatogenesis were reported (Degussa, 2003). The NOAEL for fertility corresponds therefore to the highest dose tested: 1000 mg/kg bw per day.


Short description of key information:
OECD TG 422 (GLP), oral, rat: NOAEL (fertility) = 1000 mg/kg bw.

Effects on developmental toxicity

Description of key information
OECD TG 422 (GLP), oral, rat:
NOAEL (maternal toxicity) = 300 mg/kg bw.
NOAEL (developmental toxicity) = 1000 mg/kg bw.
Additional information

The combined repeated dose reproduction/developmental screening test with dimethylmalonate in Wistar rats revealed no treatment related changes in the duration of gestation, the gestation index, parturition and pre-implantation loss compared to controls. In the low dose group post-implantation loss was increased and consequently the percentage of live pups born was statistically significantly reduced compared to controls. These changes were considered incidental and not treatment related as the effects were not observed in the mid and high dose groups. No statistically significant differences between treated and control groups were observed for the number of pregnancies, number of dams that littered, number of live litters, mean litter size, mean viable litter size, sex ratio at birth, number of pups dead at first observation or day 2 to 4 post partum, number of live pups at day 0, 3, and 4 post partum and the associated survival indices. A significantly higher percentage of male pups and lower number of females on day 4 post partum in the low dose group was considered incidental as no comparable change was observed in the mid and high dose group or at other time intervals. The mean number and mean weights of male and female pups as well as both sexes combined were otherwise not statistically significantly different from controls. No statistically significant difference in the external abnormalities of life and dead pups compared to controls was observed at all dose levels. Maternal toxicity was restricted to a reversible hepatocellular hypertrophy at 1000 mg/kg bw, with a maternal NOAEL of 300 mg/kg bw. The NOAEL for developmental toxicity was 1000 mg/kg bw per day (Degussa, 2003).

Justification for classification or non-classification