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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
screening for reproductive / developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2016

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid

Results and discussion

Results: P0 (first parental animals)

General toxicity (P0)

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, non-treatment-related
Description (incidence and severity):
The mean body weight of rats from high dose group (1000 mg/kg) was slightly lower than that of from vehicle control group throughout the premating period (for both males and females) and mating period (for males).
The values of mean body weights and mean body weight gain for rats treated with test item at and up to 1000 mg/kg did not differ significantly (p>0.05) from those of the concurrent control group rats during the gestation period and the post-natal lactation period.
Food consumption and compound intake (if feeding study):
no effects observed
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Organ weight findings including organ / body weight ratios:
effects observed, non-treatment-related
Description (incidence and severity):
A solitary incidence of statistically significant decrease was noticed in absolute weight of epididymides in male rat (in G4 dose group) which was not considered to be a treatment related change due to lack of change in relative weight of epididymides, hence not considered to be of toxicological significance.
Gross pathological findings:
effects observed, non-treatment-related
Description (incidence and severity):
Few incidental findings were observed in lungs and mediastinal lymph nodes and these comprised of reddening and abscess in lungs and enlargement of mediastinal lymph nodes. As these findings were not dose dependent and present in animals from control group as well, were therefore considered to be unrelated to treatment.
Neuropathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
no effects observed
Reproductive performance:
no effects observed
Description (incidence and severity):
There was no treatment related adverse effect on pregnancy rate, gestational length, live births and implantations.

Effect levels (P0)

Key result
Dose descriptor:
NOAEL
Effect level:
ca. 500 mg/kg bw/day (nominal)
Sex:
male/female
Basis for effect level:
body weight and weight gain

Results: F1 generation

General toxicity (F1)

Clinical signs:
no effects observed
Mortality / viability:
no mortality observed
Description (incidence and severity):
The incidence of litters with still-born pups, pups found dead in cage or cannibalised pups were very small and / or comparable across the treated and the control groups.
Body weight and weight changes:
no effects observed
Clinical biochemistry findings:
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed

Effect levels (F1)

Key result
Dose descriptor:
NOAEL
Generation:
F1
Effect level:
>= 1 000 mg/kg bw/day (nominal)
Sex:
not specified
Basis for effect level:
clinical signs
mortality

Overall reproductive toxicity

Key result
Reproductive effects observed:
no
Lowest effective dose / conc.:
1 000 mg/kg bw/day (nominal)
Treatment related:
no
Relation to other toxic effects:
reproductive effects in the absence of other toxic effects

Applicant's summary and conclusion