4-amino-m-cresol

Endpoint summary

Description of key information

According to the results of the two keys studies performed, the Lethal Dose 50 was defined as 870 mg/kg bw on rats treated by gavage. Hence, the test item was classified as Category 4 for Acute toxicity hazard by oral route according to GHS criteria and regulation.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

870 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

0.012 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 409 mg/kg bw

Additional information

Two keys studies were available to assess the potential acute toxicity of the registered substance 4 -amino-m-cresol. The two studies were no-GLP compliant, Klimisch 2 and the methods used were comparable to OECD guideline 401 method.

The first study used CF-1 female mice which were orally treated with test item at 750, 800, 850, 900, 950 and 1000 mg/kg bw after a range finding study. Mortality was observed from 800 mg/kw (1/6), 850 mg/kg bw (3/6), 900 mg/kg bw (1/6), 950 mg/kg bw (3/6) and 1000 mg/kg (6/6). Based on above, the acute oral toxicity (LD50) of 1-Hydroxy-3-methyl-4-aminobenzene when administered once orally to CF1 mouse was 908 mg/kg bw.

The second key study used Wistar rats which were orally treated with : Males: 700, 800, 900, 1000 and 1100 mg/kg bw ; Females: 800, 900, 1000, 1100 and 1200 mg/kg bw. Death occured from the low dose level as :

Males: 700 (1/5), 800 (2/5), 900 (3/5), 1000 (3/5) and 1100 mg/kg bw (5/5); Females: 800 (1/5), 900 (1/5), 1000 (2/5), 1100 (3/5) and 1200 mg/kg bw (5/5). Based on above, the acute oral toxicity (LD50) of 1-Hydroxy-3-methyl-4-aminobenzene when administered once orally to Wistar rats was 870 and 1010 mg/kg bw for males and females, respectively.

Two extrapolation calculations were performed in order to determine LD50 value for dermal and inhalation route :

Based on the available acute oral toxicity and toxicokinetics data for 4-AMINO-m-CRESOL, the acute dermal, as well as acute inhalation, toxic potential for 4-AMINO-m-CRESOL could be calculated.

The calculated inhalation toxicity value for 4-AMINO-m-CRESOL was calculated at 12.24 mg/l. When this concentration is combined with the results of in vivo eye irritation studies, it can be concluded that 4-AMINO-m-CRESOL would not have a local effect in the lungs. Based on the LC50 , calc inhal. value, 4-AMINO-m-CRESOL should be classified as Acute Tox Cat.4; H332: “harmful if inhaled”, according to the Globally Harmonized System of Classification and Labeling (GHS).

As demonstrated by in vivo toxicokinetics data, the bioavailability after application to the skin is lower than the oral bioavailability. The calculated dermal toxicity of 4-AMINO-m-CRESOL is 2409 mg/kg bw. The LD50, calc, dermal value indicates that 4-AMINO-m-CRESOL should be classified as Acute Tox Cat.5; H313: “may be harmful in contact with skin”, according to the Globally Harmonized System of Classification and Labeling (GHS).

Justification for classification or non-classification

Two acute toxicity tests were performed in mice and rats. This second study which used rats was most relevant for an extrapolation to human. The LD50 derived from this study was 870 mg/kg bw (male) and 1010 mg/kg bw (female). The selected LD50 value is 870 mg/kg bw according to precaution principle.

Hence, the test item was classified as Category 4 for Acute toxicity hazard by oral route according to GHS criteria and regulation.