Reactive Blue F08-0170

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

None

Effect on fertility: via oral route

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Additional information

A Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test was conducted to obtain information on the possible toxic effects of REACTIVE BLUE F08-0170 following repeated daily administration by oral gavage to Wistar rats. The reproductive/developmental toxicity screening test provided initial information on possible effects on male and female reproductive performance such as gonadal function, mating behaviour, conception, pregnancy, parturition and also on the development of the F1 offspring from conception to Day 4 post-partum.

There were no statistically significant differences between the Control and test item-treated groups with regard to reproductive ability or in the mating or gestation indices, or effects considered adverse or toxicologically significant in correlation with Reactive Blue F08-0170 administration.

Fertility index was lower than Control in the High dose males and females at 1000 mg/kg bw/day with 3/12 non-pregnant females, however, without attaining statistical significance and comparable with concurrent historical control data. In the absence of any test item related or adverse effects at microscopic examination of the ovaries at any of the dose levels tested, this variation was considered incidental, although the number of pregnant females with liveborn was statistically lower than control (8 versus 12, 89%,p<0.05) due to an additional female 4507 (1/12 High dose females in the 1000 mg/kg bw/day group 4, or 1/9 pregnant), which had 1 corpora lutea and 1 implantation site but was not delivered, with late embryonic death and 100% intrauterine mortality.

The mating indices were 100% in all groups. The fertility indices were 100% in the Control group, 92% in the Low and Mid dose groups and 75% in the High dose group, due to 1/12 non-pregnant females each in Group 2 and 3, values which are comparable with concurrent control data in Wistar rats, and 3/12 non-pregnant females in Group 4. Gestation index was 100% in the Control, Low and Mid dose groups and 89% in the High dose group, due to female 4507, which had one corpora lutea and one implantation site only (pregnant but not delivered, with late embryonic death).Test item administration was considered to have no impact on the duration of the mating period. Successful coitus (sperm positive vaginal smears and/or vaginal plugs) generally occurred within up to 5-6 days of pairing (cohabitation).

There was no evidence of REACTIVE BLUE F08-0170-related histological findings in the High and Control animals, or macroscopic observations from all groups in the reproductive organs. Histopathological evaluation of the male gonads as well as testicular interstitial cell structure, the spermatogenic cells representing different phases of the development and differentiation of the spermatozoons were similar in Control and High Dose males. The follicular, luteal and interstitial compartments of the ovary as well as epithelial capsule and stroma were similar histological structure in both Control and High Dose females.

No external abnormalities ascribed to test item administration were detected at the clinical or external macroscopic examinations of the pups. The sex ratios were similar in the control and treated groups. There were no effects considered adverse on the offspring weight or weight gain.

Under the conditions of this study, the no observed adverse effect level (NOAEL) for parental reproductive and F1 offspring effects is considered to be 1000 mg/kg bw/day.

Short description of key information:
Summary of reproductive toxicity data

Effects on developmental toxicity

Description of key information

Summary of reproductive toxicity data

Effect on developmental toxicity: via oral route

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Additional information

See above for summary of results of the combined repeated dose toxicity and reproductive/developmental toxicity screening test.

Justification for classification or non-classification

The above study has been ranked reliability 1 according to the Klimisch et al system. This ranking was deemed appropriate because the study was conducted to GLP and in compliance with agreed protocols. Sufficient dose ranges and numbers are detailed; hence it is appropriate for use based on reliability and animal welfare grounds.

The above results triggered no classification under the Dangerous Substance Directive (67/548/EEC) and the CLP Regulation (EC No 1272/2008). No classification for reproductive toxicity is therefore required.