4-amino-m-cresol

Endpoint summary

Description of key information

According to the result of the key study (Klimisch 1, OECD guideline 408 method, GLP compliant), the substance 1-Hydroxy-3-methyl-4-aminobenzol-sulfate induced slight toxicity in rats treated for 90 days by oral route. Effects observed were: increase in absolute spleen weight in the high dose group. The NOAEL (No observe adverse effect level) was defined as 60 mg/kg/day. Based on this result on the sulfate form, the converted NOAEL for the registered substance 4 -amino-3-methylphenol was defined at 42.6 mg/kg bw/day.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

42.6 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Additional information

One study quoted as Klimisch 1 was available to assess the potential toxicity of 1-Hydroxy-3-methyl-4-aminobenzol-sulfate. The test was performed according to OECD guideline 408 method and was GLP compliant. Wistar rats were used and was assignated to 20 animals per sex per dose which were 0 (vehicle), 15, 60, 120 mg/kg day. Rats were treated orally by gavage daily, for a period of 90 days with a volume dose of 10 mL/kg. An additional groups of 5 animals per sex per dose was used as recovery group for high dose level after a 4 weeks treatment free period.

Animals were observed twice daily for mortality/morbidity and once daily for clinical abnormalities. Body weight and food consumption were recorded weekly. A detailed ophthalmological investigation as well as an evaluation of auditory function and reflexes, according to a modified Irwin screen test (FOB) were performed on 5 animals/sex/group with special regard to awareness, co-ordination and autonomous nervous system functions. The investigations were conducted prior to treatment, after week 6, at the end of the treatment period and at the end of week 17 (recovery groups). Haematology and clinical chemistry evaluations were performed in 20 animals/sex/dose at Day 0, and after 6 and 13 weeks in all dose groups and after 17 weeks in the recovery group. The urinalysis was performed in the 5 animals/sex/dose at Day 0, and after 6 and 13 weeks in all dose groups and after 17 weeks in the recovery group. At the end of the treatment period, all animals were killed and subjected to a detailed necropsy. Recovery group animals were sacrificed after Week 17 of the study. Selected organs were weighed. A wide range of organs/tissues of the control and high dose animals was examined histopathologically. In addition, all gross lesions noted were examined microscopically.

The only test substance related finding was an increase in absolute spleen weight in high dose females (statistically significant) and in high dose males (not statistically significant). In the high dose recovery group an increase in absolute spleen weight was not observed. No treatment related effects were observed in body weight gain, food efficiency, urinalysis, hematology, clinical chemistry, gross pathology and histopathology parameters at any dose levels.

Based on above, oral administration of to male and female Wistar (BOR: WISW) rats at dose levels of 15, 60 and 120 mg/kg bw by oral gavage for a period of 90 days revealed a NOAEL of 60 mg/kg bw.

Based on this result on the sulfat form, the converted NOAEL for the registered substance 4 -amino-3-methylphenol was defined at 42.6 mg/kg bw/day (calculation based on molecular weight).

Justification for classification or non-classification

According to the result of the key study (Klimisch 1, OECD guideline 408 method, GLP compliant), the substance 1-Hydroxy-3-methyl-4-aminobenzol-sulfate induced slight toxicity in rats treated for 90 days by oral exposure as increase in absolute spleen weight in the high dose group. The NOAEL (No observeadverse effect level) was defined as 60 mg/kg/day.

Based on this result on the sulfat form, the converted NOAEL for the registered substance 4 -amino-3-methylphenol was defined at 42.6 mg/kg bw/day (calculation based on molecular weight).