4-amino-3-nitrophenol

Endpoint summary

Description of key information

Based on the results of the key studies (Hill, 1992, Klimisch 1, OECD 407 ; Brownlie, 1997, Klimisch 1, OECD 408) , the No Observed Adverse Effect Level (NOAEL) of the test article 4 -amino-3 -nitrophenol when administered orally by gavage to rats was defined at 250 mg/kg/day. The Test Article was not classififed for STOT-RE according to the CLP regulation.

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

250 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Additional information

Two key studies were availables for Test Item Repeated oral dose toxicity assessment : A first 28 Days repeated study was performed (Hill, 1992, Klimisch 1, OECD 407 ). The test article was administered, by gavage, once daily to 4 groups of Crl:CD-(SD)BR rats (10/sex) for 28 days. The test substance was administered at dosage levels of 100, 250 or 600 mg/kg bw. The control group received the vehicle (carboxymethylcellulose).Two animals (high dose group) died during the study (laboured respiration). All treated groups showed orange fur-staining, from day one. In the high dose group the following effects were observed: scabbing, perinasal staining, mild convulsions, significantly decreased body weight in the males. The dose level without adverse effects was 250 mg/kg bw.The NOAEL was defined at 250 mg/kg bw per day.

Based on this study, selected dose was defined at 0, 50, 100, 250 mg/kg/day for a 90 Days repeated dose toxicity study (Brownlie, 1997, Klimisch 1, OECD 408). The purpose of this GLP compliant study was to assess the toxicity of the test article Imexie FN when administered orally, by gavage, to the rat daily for 13 weeks. Animals were observed daily, body weight and food consumption was recorded weekly. Ophthalmoscopy was performed before and after the exposure on control and high exposure groups. Haematology and blood chemistry investigations and urine analysis were performed at the end of the experiment. At the termination all animals were subjected to necroscopy. Orange coloured urine was reported in all exposed groups demonstrating renal elimination of Terst Article and can therefore be considered a sign of systemic exposure. An increase in liver weights (+15%, relative weight) relative to control group was reported at the highest exposure group (males, 250 mg/bw/day). No abnormal histopathological findings in any tissues studied related to Test Item exposure was reported.

The NOAEL was set at 250 mg/kg bw per day. Based on liver weight increase, the NOEL was set at 50 mg/kg bw per day.

Justification for classification or non-classification

Based on the results of the key studies (Hill, 1992, Klimisch 1, OECD 407 ; Brownlie, 1997, Klimisch 1, OECD 408), the No Observed Adverse Effect Level (NOAEL) of the test article 4 -amino-3 -nitrophenol when administered orally by gavage to rats was defined at 250 mg/kg/day. The Test Article was not classififed for STOT-RE according to the CLP regulation.