m,m'-[carbonylbis[imino(3-methoxy-p-phenylene)azo]]bis(benzenesulphonic) acid, compound with 2,2'-iminodiethanol (1:2)

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

In an OECD 421 study (OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)) three groups of ten male and ten female CD rats received Bayscript Yellow GGN at doses of 10, 30 or 70 mg/kg/day by oral gavage administration. Males were treated daily for two weeks before pairing, up to necropsy after a minimum of four consecutive weeks. Females were treated daily for two weeks before pairing, throughout pairing, gestation and until Day 12 of lactation. Females were allowed to litter, rear their offspring and were killed on Day 13 of lactation. The F1 generation received no direct administration of the test item; any exposure was in utero or via the milk. 

During the study, for adult animals assessments of clinical condition, body weight, food consumption, estrous cycles, pre-coital interval, mating performance, fertility, gestation length, organ weight and macroscopic pathology and histopathology investigations were undertaken.

For the offspring, clinical condition, litter size and survival, sex ratio, body weight, ano‑genital distance and nipple counts (males only), and macropathology were also assessed. Blood samples were collected from all adult animals at termination and from selected offspring on Day 4 and Day 13 of age for thyroid hormone analysis. 

The oral administration of Bayscript Yellow GGN up to and including 70 mg/kg/day for four weeks in males and for two weeks prior to pairing, throughout gestation and up to Day 13 of lactation in females, was generally well tolerated. Clear adverse reductions in body weight performance and food consumption were evident in the parental animals given 70 mg/kg/day throughout the study, although in the absence of any change in general clinical condition. Test item-related histopathological changes were evident in the kidneys, manifest as an increase in both incidence and severity of tubular collecting duct basophilia, tubular dilatation and intratubular crystals in the kidneys of animals receiving 30 or 70 mg/kg/day, associated with increases in kidney weights in both sexes and with gross changes of pale and granular kidneys seen at necropsy; these kidney changes were considered to be adverse. It was therefore concluded that within the context of this study, the No Observed Adverse Effect Level for systemic toxicity was 10 mg/kg/day.

There was no evidence of any adverse effects on mating performance or fertility of the adult animals or on the survival or development of the F1 offspring. The reduction in the number of uterine implantations at 70 mg/kg/day (and as a consequence litter size) was not related to any other changes in reproductive parameters, such as post implantation loss. This effect, however, was statistically significant and outside of the historical control values (representing 22 OECD TG 421 and 422 studies). Although this effect is considered likely to be secondary to the lower maternal body weight at the time of mating, it is considered to be of uncertain aetiology and therefore potentially adverse. It was therefore concluded that within the context of this study, the NOAEL for reproductive performance was 30 mg/kg/day.

Effect on fertility: via oral route

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

30 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

GLP guideline study

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 study available

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Toxicity to reproduction: other studies

Description of key information

No data.

Justification for classification or non-classification

In an OECD 421 study (OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)) there was no evidence of any adverse effects on mating performance or fertility of the adult animals or on the survival or development of the F1 offspring. The reduction in the number of uterine implantations at 70 mg/kg/day (and as a consequence litter size) was not related to any other changes in reproductive parameters, such as post implantation loss. This effect, however, was statistically significant and outside of the historical control values (representing 22 OECD TG 421 and 422 studies). Although this effect is considered likely to be secondary to the lower maternal body weight at the time of mating, it is considered to be of uncertain aetiology and therefore potentially adverse. It was therefore concluded that within the context of this study, the NOAEL for reproductive performance was 30 mg/kg/day. According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification is therefore not justified.