Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

Toxicity for reproduction: negative

Developmental toxicity: negative

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available

Effects on developmental toxicity

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available

Justification for classification or non-classification

One study performed on similar substance is available for toxicity to reproduction.

In this study, groups of 10 male and 20 female rats were fed 0, 0.37, 0.72, 1.39 or 5.19 % (equivalent to 0, 185, 360, 695 and 2595 mg/kg bw/day) of the tested substance in their diet through two parental (P1, P2) and two filial (F1A/B and F2A/B) generations (F1A was P2). Mating occurred after 27 weeks of exposure, for both P1 and P2 generations. Fertility indices were found to be low in the two filial generations, but it is unclear from the text whether they were significantly lower than the controls, as the animals in control groups also showed low fertility indices. Furthermore, a slight growth suppression was observed, mainly at the high test levels in F1 and F2 pups. No anomalies were detected regarding growth, litter size, pup weight, gross pathology, implantation sites, resorptions sites, live fetuses indices, appearance and anatomy and structure (Blackmore et al., 1969). The JECFA concluded that the NOAEL is 695 mg/kg bw/day, considering the slight growth suppression observed mainly at the high test level in F1 and F2 pups. The JECFA has used this NOAEL, together with the NOAEL from the rat study described below (Serota et al., 1977b) to establish the ADI of 0-7 mg/kg bw/day.

Two studies related to teratogenicity are available.

In the first study, groups of 24, 19, 20, 21 and 16 pregnant rats received 0, 15, 30, 100 and 200 mg/kg bw/day of the dye, respectively, by gavage during gestational days 0-19. No dye-induced effects were observed in terms of early or late deaths, resorptions, pre-implantation loss, litter size and average fetus weight (Collins, 1974). The Panel concluded that the NOAEL of this study amounts to 200 mg/kg bw/day, the highest dose tested.

A second teratogenicity study was conducted in rabbits. In this study groups, 14 rabbits were fed 0, 200 or 700 mg/kg bw/day by gavage from gestational day 6 to 18. No compound-related effects were observed regarding appearance and behaviour, body weight, gross necropsy findings, implantation, litter data, or other fetal abnormalities (Reno, 1974). The Panel concluded that the NOAEL in this study would be the highest dose tested being 700 mg/kg bw/day, and thus in line with the NOAELs taken from the study of Blackmore et al. (1969) from which JECFA derived an ADI of 0-7 mg/kg bw/day (JECFA, 1980).

Based on the available test results, no classification for toxicity to reproduction or for developmental toxicity is requested.