5-amino-o-cresol

Endpoint summary

Description of key information

According to the results of the key study (Klimisch 2), the Lethal Dose of the registered substance 4 -amino-2 -Hydroxytoluene was defined as 3600 mg/kg bw. Hence, the substance was not classified for Acute Hazard Oral according to CLP regulation.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

3 600 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

42 570 mg/m³ air

Quality of whole database:

extrapolated from acute oral toxicity study. The calculated inhalation toxicity value for 4-AMINO-2-HYDROXYTOLUENE (42.57 mg/L) was reflected in the respective oral LD50 values.

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 688 mg/kg bw

Quality of whole database:

extrapolated from acute oral toxicity study

Additional information

The objective of this no GLP compliant study (quoted as Klimisch 2) was to determine the acute toxicity of 4-Amino-2-hydroxytoluene after oral administration. Male and female rats of CFY strain weighing between 90-119 g were used in the study. Animals were fasted before treatment. The test substance was prepared as a 10% suspension in aqueous gum tragacanth (0.5%) containing sodium sulphite (0.05%) in order to be used for rat gavage. The results of preliminary range finding tests indicated that the median lethal oral dose (LD50), was in the region of 2500 to 6400 mg/kg bw. Dosing was then extended to larger groups of rats (five males and five females) in order to locate the median lethal dose more precisely in the main test. In the main study, 5 rats/sex/dose were administered the test substance via gavage at dose levels of 0, 1600, 2500, 4000 and 6400 mg/kg bw. Animals were observed for mortalities and signs of toxicity daily for 14 days. Slightly depressed bodyweight gain was observed during the first week of observation in the surviving female rat treated at 4000 mg/kg, but returned to normal during the second week of observation compared with controls.

Shortly after dosing clinical signs observed were lethargy, piloerection and decreased respiration rate. These signs were accompanied by ataxia in rats treated above 1600 mg/kg bw and by fine body tremors and increased lacrimation in rats treated above 2500 mg/kg bw. Recovery of animals, as judged by external appearance and behaviour, was apparently complete within six days of treatment.Mortality observed at individual dose levels was as follows:

- 1600 mg/kg bw: 0/5 male and 0/5 female;

- 2500 mg/kg bw: 0/5 male and 0/5 female;

- 4000 mg/kg bw: 4/5 males and 4/5 females;

- 6400 mg/kg bw: 5/5 males and 5/5 females

Autopsy of animals who died during the study revealed darkening of the liver, kidneys, and spleen and injection of mesenteric and intestinal blood vessels. Terminal necropsy findings were normal.

Based on above, The acute median lethal oral dose of 4-amino-2-hydroxytoluene in rats was determined to be 3600 (95% confidence limits: 3100-4000) mg/kg bw.

Justification for classification or non-classification

According the results of the key study (Klimisch 2), the Lethal Dose of the registered substance 4 -amino-2 -Hydroxytoluene was defined as 3600 mg/kg bw. Hence, the substance was not classified according to CLP regulation.

The calculated inhalation toxicity value for 4-AMINO-2-HYDROXYTOLUENE (42.57 mg/L) was reflected in the respective oral LD50 values. When these concentrations are combined with the results of in vitro eye irritation studies, it can be concluded that 4-AMINO-2-HYDROXYTOLUENE would not have a local effect in the lungs. Based on the calculated LC50 calc, inhal. value, 4-AMINO-2-HYDROXYTOLUENE should be classified as Acute Tox Cat.5; H333: “may be harmful if inhaled”, according to the Globally Harmonized System of Classification and Labeling (GHS) and Not Classified according to CLP criterias.

The calculated acute dermal toxicity of 4-AMINO-2-HYDROXYTOLUENE (LD50, calc, dermal) is 5688 mg/kg bw based on acute oral toxicity study. The LD50,calc,dermal value indicates that 4-AMINO-2-HYDROXYTOLUENE 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) and not classified according to CLP regulation.