2-(4-amino-2-nitroanilino)ethanol

Endpoint summary

Description of key information

Based on te result of the key study (NTS, 1979, Klimisck 2, equivalent to OECD guideline), the NOAEL of the registered substance HC Red No 3 for repeated oral dose toxicity was defined at 250 mg/kg bw/day. The registered item was not classified for STOT-RE according to CLP criteria.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

250 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

A key study klimisch 2 and 3 supporting studies klimisch 2

Additional information

One key study is available : NTS study, Klimisch 2, 1979

F344/N rats were used in this study. Animals were exposed during 13 weeks, daily , 5 days per weeks. Clinical examination, bodyweights and morbidity observations were performed. At the termination of the study, necropsy and histopathology were performed on vehicle group and high dose group. Further analysis of thyroid and kidneys were performed. HC Red n° 3 was administered by gavage at dose levels of 0, 62, 125, 250, 500 and 1000 mg/kg bw/d to male and female rats (10 animals per dose).

None of the rats died before the end of the studies. The urine of dosed animals was orange to purple throughout the studies. Final body mean weights relative to vehicle controls were 7% lower for male rats that received 1000mg/kg and 5% lower for the male rat group that received 500 mg/kg. Final body mean body weights of dosed female rats were greater than those of the vehicle controls.

Granules of a brown to golden brown pigment were found in the cytoplasm of the thyroid gland follicular epithelial cells in 10/10 males and 10/10 females that received 1000 mg/kg and 10/10 males and 7/10 females that received 500 mg/kg but not in any of the rats that received 250 mg/kg. Similar pigment was found in the cytoplasm of convoluted tubular epithelial cells in the kidneys of all rats that received 1000 mg/kg, in 7/10 males and 10/10 females that received 500 mg/kg, and 6/10 males and 7/10 females that received 250 mg/kg. No other microscopic observations attributable to HC red No3 administration were noted. . The NOAEL was defined as 250 mg/kg bw/day based on the bodyweight decrease. In this no GLP compliant study, animals were treated only 5 days per week instead of 7 required in the OECD guideline. Complete analysis were not performed (as haematology, clinical biochemistry, urinalysis). This study did not follow modern standard for a 90 days repeated toxicity study but was relevant.

A supporting study is available : NTS study, Klimisch 2, 1979, suporting study

B6C3F mice were treated orally witch 0, 15, 31, 62, 125 and 250 mg/kg bw/d with the registered item during 13 weeks (10 animals per dose) with same method as the key study.

All deaths that occurred were related to gavage technique. The final mean body weights of males that received doses of 250 mg/kg bw/d were 7% lower than those of controls. Final body weights of dosed female were comparable to those of controls. The urine of all dosed animals was red throughout the studies. No compound-related gross or microscopic pathologic effects were recorded.

In mice, based on the body weight decrease observed at 250 mg/kg bw/d the NOAEL is 125 mg/kg bw/d.

Two other 14 days repeated dose toxicity studies were available (considered as supporting study, from NTP, 1979, Klimisch 2) :

In this 14-day Oral Toxicity Study in F344/N rats and B6C3F1 mice, HC Red n°3 was administered daily in diet in both sexes at dose levels of 0, 62, 125, 250, 500 and 1000 mg/kg bw/d in male and female rats (5 animals per dose), and 0, 31, 62, 125, 250 and 500 mg/kg bw/d in male and female mice (5 animals per dose). Animals were observed twice daily for signs of toxicity. Clinical observations were recorded on the day of necropsy. Animals were weighed at the start of the study, and on day 15. Necropsies were performed on all animals. No histopathology examination was performed.

For rats, all animals survived to the end of the studies. The urine of all dosed animals was maroon to orange throughout the studies. Differences in mean body weight gains were not dose related. Dark thyroid glands were observed in 5/5 male rats that received 1000 mg/kg/d, 2/5 males that received 500 mg/kg/d and 2/5 males that received 250 mg/kg/d.

For mice, all animals survived to the end of the studies. The urine of all dosed animals was maroon to orange throughout the studies. Mean body weight gains were comparable between dosed or control groups.

In the 14-day gavage rat study, the NOAEL was 1000 mg/kg bw/d and in mice study, the NOAEL was 500 mg/kg bw/d.

Justification for classification or non-classification

Based on te result of the key study (NTS, 1979, Klimisck 2, equivalent to OECD guideline), the NOAEL of the registered substance HC Red No 3 for repeated oral dose toxicity was defined at 250 mg/kg bw/day. The registered item was not classified for STOT-RE according to CLP criteria.