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Effects on fertility

Description of key information

There is no reproductive toxicity study with the target substance available. Data generated with the category substances LAB and LABS Na were considered pivotal to this endpoint. The target substance is considered to have a parental NOAEL of 50 mg/kg/day and an NOAEL for offspring of 50 mg/kg/day.

Effect on fertility: via oral route
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
50 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

There is no reproductive toxicity study with the target substance available. Data generated with LAB and LABS Na was considered pivotal to this endpoint.

LAB: Groups of 30 female and 30 male rats were exposed to concentrations of 0, 5, 50 and 500 mg/kg/day of test substance by oral gavage beginning ten weeks before mating. Animals were then mated. The resulting generation was also exposed to the test substance and mated. Exposure continued through the mating period, and in females through the gestation and lactational periods. All animals were sacrificed and necropsied after exposure. Pups not used for mating were sacrificed at weaning. During the study, animals were observed for clinical signs, mortality, and body weight. Pups were examined for viability and body weight gain. Reproductive indices were also calculated. The NOAEL for parental toxicity was 50 mg/kg/day and the LOAEL was 500 mg/kg/day on reduced weight gain and litter size in the high dose group. The NOAEL for offspring was 50 mg/kg/day based on reduced body weight gain and survival in the high and mid-dose groups. The LOAEL for offspring was 500 mg/kg/day.

LABS Na: was fed for 84 days to 4 groups of weanling rats for two years (three generations). No significant effects were observed at the highest dose tested and the resulting NOAEL for the parental and both offspring generations was 350 mg/kg bw (0.5%).

The target substance is considered not to be toxic to reproduction.

Effects on developmental toxicity

Description of key information

There is no reproductive toxicity study with the target substance available. Data generated with the category substances LAB and LABS Na were considered pivotal to this endpoint. The target substance is considered to have an NOAEL of 125 mg/kg/day for maternal toxicity and embryotoxicity.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
125 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

There was no developmental toxicity study available with the target substance. Data generated with the target substances LAB and LABS Na is considered pivotal to this endpoint.

Groups of 24 mated female rats were exposed to concentrations of 0, 125, 500 and 2000 mg/kg bw/day of LAB by oral gavage during days 6 -15 of gestation (OECD guideline 414). On day 20 of gestation, the animals were sacrificed and the uterine contents examined. Pups were removed by caesarean section and soft tissue and skeletal examinations performed. The LOAEL for maternal toxicity was 500 mg/kg bw/day based on reduced body weight gain. The NOAEL for maternal toxicity was 125 mg/kg bw/day. The LOAEL for embryotoxicity was also 500 mg/kg bw/day based on increased incidence of incomplete ossification. The NOAEL for embryotoxicity was also 125 mg/kg bw/day. Since no embryotoxicity was seen at doses that were not toxic to the maternal animals, the test substance is not classified as teratogenic.

As described above, the reproductive toxicity potential of LAB was also tested in an OECD guideline 416 study. The NOAEL for parental toxicity was 50 mg/kg/day and the LOAEL was 500 mg/kg/day on reduced weight gain and litter size in the high dose group. The NOAEL for offspring was 50 mg/kg/day based on reduced body weight gain and survival in the high and mid-dose groups. The LOAEL for offspring was 50 mg/kg/day.

Pregnant female mice were exposed to LABS Na via gavage on days 6 -15 of gestation. Increased mortality was observed at the two highest doses (300 and 600 mg/kg bw/day). These doses also exhibited retarded weight gain and adverse signs in the necropsy. Pregnancy was comparable, however, for all groups. At doses without maternal toxicity, no differences were observed in any parameters. Because of the very wide range between the 2 mg/kg and 300 mg/kg doses, the maternal NOAEL of 2 mg/kg bw/day must be considered very conservative. The NOAEL for teratogenicity was 300 mg/kg bw/day.

In a second developmental toxicity study, female rats were given LABS Na orally in distilled water from gestation days 6 to 15 during pregnancy. Some effects such as decreased weight gain and transient diarrhea occurred at the highest dose. Pregnancy rates were comparable at all doses. Litter parameters were not significantly affected at any dose. No significant differences were observed in visceral anomalies or skeletal variants, with the exception of a marginal retardation of sternabral ossification at the highest dose. NOAEL was 300 mg/kg for both maternal and teratogenicity.

Justification for classification or non-classification

Additional information

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