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Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

The test substance did not show toxicity to reproduction in an OECD 422 guideline study.

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subacute
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

In a GLP-compliant repeated dose toxicity study performed according to OECD guideline 422, the test substance formulated in water, was administered daily by oral gavage to SPF-bred Wistar Han rats at dose levels of 63, 250 and 1000 mg/kg bw/day (10 rats/sex/dose level). The dose levels were based on a dose-range finding study performed previously. Concurrent controls (10 rats/sex) received the vehicle only. Males were exposed for 29 days, i.e. 2 weeks prior to mating, during mating, and up to termination. Females were exposed for 41-55 days, i.e. during 2 weeks prior to mating, during mating, during post-c oitum, and during at least 4 days of lactation. The following observations and examinations were evaluated: mortality / viability, clinical signs (daily), functional observations and locomotor activity (end of treatment), body weight and food consumption (at least at weekly intervals), clinical pathology (end of treatment), macroscopy at termination, organ weights and histopathology on a selection of tissues, and reproduction/developmental parameters, consisting of mating, fertility and conception indices, precoital time, number of corpora lutea and implantation sites, gestation index and duration, parturition, maternal care, sex ratio and early postnatal pup development (mortality, clinical signs, body weights and macroscopy). Accuracy, homogeneity and stability of formulations were demonstrated by analyses. Local adverse effects were observed in the forestomach at 1000 mg/kg bw/day in both sexes. This was indicated by macroscopic changes (thickened fore stomach; irregular surface and grown together with the diaphragm) and microscopic alterations (erosion/ulceration with submucosal granulation tissue, hyperplasia, edema) which may reflect a response to damage of the forestomach epithelium by the test substance, including an interruption of the protective forestomach epithelium. No systemic parental toxicity was observed up to the highest dose level tested (1000 mg/kg bw/day). Slightly lower body weight (gain), accompanied by lower food consumption, was noted in males at 1000 mg/kg bw/day, which may be secondary to the local effects on the forestomach and was considered not to reflect systemic toxicity of the test substance. Particularly, the three males with the lowest overall lower body weight gain had marked histopathological findings at the forestomach. Microscopic examination showed an increased incidence of minimal mucosal hypertrophy in the cecum of females at 1000 mg/kg bw/day, which was regarded not to be adverse. A subtle increase in incidence of increased lymphocytolysis in the thymus was noted in females at 1000 mg/kg bw/day. One of the two affected females also had a marked forestomach ulcer and, therefore, the increased lymphocytolysis in the thymus of this female was regarded to be related to stress. Based on this and in view of the incidence and minimal severity, this finding in the thymus was regarded not to be adverse. No reproductive or developmental toxicity was observed up to the highest dose level tested (1000 mg/kg bw/day). In conclusion, treatment with the test substance by oral gavage in male and female Wistar Han rats at dose levels of 63, 250 and 1000 mg/kg bw/day revealed local parental toxicity (morphological changes in the forestomach) at 1000 mg/kg bw/day. No systemic parental toxicity, reproduction toxicity or developmental toxicity was observed for treatment up to 1000 mg/kg bw/day. The NOAEL for local toxicity was determined to be 250 mg/kg bw/day. The NOAEL for systemic parental toxicity, reproduction toxicity or developmental toxicity was determined to be >1000 mg/kg bw/day, respectively.

Effects on developmental toxicity

Description of key information

The test substance did not show any developmental effects in an OECD 422 guideline study.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Study duration:
subacute
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

Justification for classification or non-classification

Based on the available information classification for toxicity to reproduction or developmental toxicity is not warranted in accordance with EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008.