Sodium bis[2-[(4,5-dihydro-3-methyl-5-oxo-1-phenyl-1H-pyrazol-4-yl)azo]benzoato(2-)]chromate(1-)

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

In an OECD 422 study no signs of toxicity to fertility have been found up to the highest dose level of 1000 mg/kg tested.

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

The test item was administered by gavage to groups of 10 male and 10 female Wistar rats (F0 generation) at dose levels of 0 mg/kg body weight/day (mg/kg bw/d; test group 0), 100 mg/kg bw/d (test group 1), 300 mg/kg bw/d (test group 2) and 1000 mg/kg bw/d (test group 3). Drinking water containing 0.5% sodium carboxymethyl cellulose served as vehicle, control animals were dosed daily with the vehicle only. The duration of treatment covered a 2-week premating period and mating in both sexes (mating pairs were from the same dose group) as well as entire gestation and lactation period in females up to one day prior to the day of schedule sacrifice of the animals. Regarding clinical examinations, signs of general systemic toxicity were not observed in male or female parental animals of test groups 1-3 (100, 300 and 1000 mg/kg bw/d) during the entire study period. Fertility indices for male and female animals were not impaired by test-substance administration even at a dose level of 1000 mg/kg bw/d. In addition, live birth indices of pups in all test groups were not influenced. The viability index as indicator for pup mortality was not altered. Concerning clinical pathology, no treatment-related, adverse effects were observed up to a dose level of the compound of 1000 mg/kg bw/d. There were no test item related terminal body-weight changes, organ-weight changes, gross findings or microscopic findings in both the non-reproductive and reproductive organs. The minor differences in mean spleen and thymus weight in males treated with 100 and 300 mg/kg bw/d are considered unrelated to the treatment based on the absence of a dose-response relationship and by the absence of relevant histopathologic findings in these organs in high-dose group animals. In the mesenteric lymph node of 1000 mg/kg bw/d Oracet Yellow 160 FA-treated animals few macrophage aggregates were observed. It is however not uncommon to see a low incidence of macrophage aggregates within the mesenteric lymph node in healthy control Wistar rats (Johnson R.C. et al., 2013) and therefore this finding is considered spontaneous and not test item related. In the lung of a single female of the group treated with 300 mg/kg bw/d a widespread fine, gritty, foreign alveolar content was present. The finding was accompanied by the presence of foamy alveolar macrophages and multiple cholesterol granuloma (with foreign body-type multinucleated macrophages). Further this animal showed signs of early emphysema. Grossly this change was characterized by multifocal yellow discoloured lobes. The combination of findings strongly suggests that the compound accidentally entered the lung. There were no morphological findings in the reproductive organs of either sex which could be attributed to the test item. The spermatogenic staging profiles were normal for all males examined.

Under the conditions of this Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test, the oral administration of the test item by gavage to Wistar rats revealed no signs of systemic toxicity up to a dose level of 1000 mg/kg bw/d in animals of both sexes. Thus, the no observed adverse effect level (NOAEL) for general systemic toxicity was 1000 mg/kg bw/d for male and female Wistar rats. The NOAELfor reproductive performance and fertility was also set to 1000 mg/kg bw/d formale and female Wistar rats. The NOAEL for developmental toxicity was 1000 mg/kg bw/d.

In conclusion, regarding clinical pathology parameters, the no observed adverse effect level (NOAEL) for this test compound in rats of both sexes is at least 1000 mg/kg bw/d.

Effects on developmental toxicity

Description of key information

In an OECD 422 study no signs of toxicity to development have been found up to the highest dose level of 1000 mg/kg tested.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008  

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. As a result the substance is not considered to be classified for reproduction and development under Regulation (EC) No 1272/2008.