5-amino-o-cresol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1975

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study meets basic scientific principles, non GLP study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1975

Report date:

1975

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Acute oral toxicity or LD50 value was determined by administration of test substance to 4 dose groups (5 rats/sex/group). Subsequently, observations of effects such as mortality and clinical signs were made for 14 days. Body weights were measured prior to dosing, and on Day 7 and 14 of dosing. A gross necropsy was performed on the day of death or after terminal sacrifice on all animals.

GLP compliance:

no

Remarks:

Pre-GLP

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

5-amino-o-cresol

EC Number:

220-618-6

EC Name:

5-amino-o-cresol

Cas Number:

2835-95-2

Molecular formula:

C7H9NO

IUPAC Name:

5-amino-2-methylphenol

Constituent 2

Reference substance name:

4-Amino-2-Hydroxy Toluene

IUPAC Name:

4-Amino-2-Hydroxy Toluene

Test material form:

not specified

Details on test material:

- Name of test material: 4-Amino-2-Hydroxy Toluene
- TSIN #: Not reported
- Substance type: Pure active substance
No other information on details on test material was provided in the study report.

Test animals

Species:

rat

Strain:

other: CFY strain

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 90-119 g
- Fasting period before study: Overnight before treatment
No other information on test animals was provided in the study report.

ENVIRONMENTAL CONDITIONS
No information on environmental conditions was provided in the study report.

IN-LIFE DATES: Not reported

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: aqueous gum tragacanth (0.5%) containing sodium sulphite (0.05%)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 10% suspension in aqueous gum tragacanth (0.5%) containing sodium sulphite (0.05%).

MAXIMUM DOSE VOLUME APPLIED: 64 mL/kg bw

DOSAGE PREPARATION: The test substance was prepared as a 10% suspension in aqueous gum tragacanth (0.5%) containing sodium sulphite (0.05%).

Doses:

Range finding study: 0, 400, 1000, 2500 and 6400 mg/kg bw
Main study: 0, 1600, 2500, 4000, 6400 mg/kg bw

No. of animals per sex per dose:

Range finding study: 2 animals/sex/dose group
Main study: 5 animals/sex/dose group

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for mortalities and signs of toxicity daily for 14 days. Body weights were measured prior to dosing, and on Day 7 and 14 of dosing.
- Necropsy of survivors performed: Yes, a gross necropsy was performed on the day of death or after terminal sacrifice on all animals. All rats that died were examined macroscopically in an attempt to identify the target organs, and those animals surviving terminally were similarly examined to detect possible residual damage.

Statistics:

The LD50 and its 95% confidence limits were calculated from the mortality data by the method of Weil C.S. (1952). Biometrics, 8, 249.

Results and discussion

Preliminary study:

- No mortalities were observed at any dose levels except at the highest dose level (6400 mg/kg bw) where all animals died in less than 26 hours. 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.

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

3 600 mg/kg bw

Based on:

test mat.

95% CL:

3 100 - 4 000

Mortality:

- 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

Clinical signs:

other: - Signs of reaction to treatment observed shortly after dosing, included lethargy, piloerection and decreased respiratory rate. These sign were accompanied by ataxia in rats treated above 1600 mg/kg bw and by fine body tremors and increased lacrimation in

Gross pathology:

- Autopsy revealed darkening of the liver, kidneys, and spleen and injection of mesenteric and intestinal blood vessels. Necropsy findings were normal.

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Remarks:

Migrated information

Conclusions:

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. No classification applied according to CLP regulation.

Executive summary:

The objective of this study 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 the range finding study, 2 rats/sex/dose were administered the test substance via gavage at dose levels of 0, 400, 1000, 2500 and 6400 mg/kg bw. Mortalities were observed only at the highest dose level (6400 mg/kg bw) where all animals died in less than 26 hours. 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. Body weight gain was normal in rest of the test group animals.

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.