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Description of key information

According the result of the key studies (Rush, 2005, Klimisch 1, OECD 408 for Definitive Study, GLP, Dose Range Finding Study and Definitive Study), The No Adverse Effect Level NOAEL of the test item HC Yellow No. 2 in a 90 Days Repeated Dose Toxicity Test in rats exposed by oral route was defined at 50 mg/kg/day. No adverse and toxicologically relevant effect was observed in the study. Hence, the test item was not classfified.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
50 mg/kg bw/day
Study duration:
subchronic
Species:
rat

Additional information

A first key study was performed in order to define toxic dose levels of the test item in rats during a 14 Days Repeated Dose Toxicity Test by oral route. Based on the results of this study, oral administration of the Test Item in the rat for 14 consecutive days at up to 600 mg/kg/day did not produce any treatment-related mortality or clinical signs of toxicity. In addition, there were no remarkable changes in the clinical pathology data, gross necropsy data, or organ weight data to suggest a treatment-related effect.

The selected dose for the second key study (Definitive 90 Days Repeated Dose Toxicity, Rush, Klimisch 1, OECD 408, GLP, 2005) was 0, 5, 20 and 50 mg/kg/day. The test article and vehicle control material were administered once daily, by oral gavage, for 91 consecutive days. General health/mortality and moribundity checks were performed twice daily, in the morning and afternoon. Cage-side observations were performed on all animals approximately 30 to 90 minutes after dosing. Detailed clinical observations were performed weekly on all animals. Functional observation battery (FOB) observations were conducted on 10 rats/sex/group on days -1, 26, 40 and 89. Individual body weights and food consumption were recorded weekly. Ophthalmological examinations were performed on all animals once prior to treatment (days -6/-7) and on days 84 (females) and 85 (males). Recovery animals received ophthalmological examinations on days 114 (females) and 115 (males). Blood and urine samples were collected from all animals for analysis of selected clinical pathology parameters on the day of scheduled euthanasia. All animals were subjected to a complete gross necropsy examination upon death or scheduled euthanasia. Sperm was collected from each male rat following euthanasia for assessment of sperm enumeration, motility and morphology. Fresh organ weights were obtained at scheduled euthanasia from selected organs.

The oral administration of HC Yellow n° 2 up to 50 mg/kg bw/da in the rat for 91 consecutive days produced no mortality or notable signs of systemic toxicity. In addition, there were no significant microscopic lesions observed following histopathological evaluation of selected organs/tissues. A variety of statistically significant changes were observed in the 5, 20 and 50 mg/kg bw/d animals, but these were seemed of no toxicological significance. Based on the findings in this study, the no-observed-adverseeffect level (NOAEL) for oral administration of HC Yellow n° 2 to rats for at least 91 consecutive days is 50 mg/kg bw/day.

Justification for classification or non-classification

According the result of the key studies (Rush, 2005, Klimisch 1, OECD 408 for Definitive Study, GLP, Dose Range Finding Study and Definitive Study),The No Adverse Effect Level NOAEL of the test item HC Yellow No. 2 in a 90 Days Repeated Dose Toxicity Test in rats exposed by oral route was defined at 50 mg/kg/day. No adverse and toxicologically relevant effect was observed in the study. Hence, the test item was not classfified.