4-amino-m-cresol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From June 27, 1979 to July 20, 1979

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Basic data given, followed methods similar to guideline, no GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1984

Report date:

1984

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Acute oral toxicity (LD50) of test substance was determined in female mice, by a single oral administration of test substance at six dose levels. After treatment, animals were observed for clinical signs, cage side observation and mortality for 14 days. A gross necropsy was performed on all animals on the day of death or after terminal sacrifice. The method followed in the study was comparable to the OECD 401 guideline.

GLP compliance:

no

Remarks:

(pre-GLP)

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

4-amino-m-cresol

EC Number:

220-621-2

EC Name:

4-amino-m-cresol

Cas Number:

2835-99-6

Molecular formula:

C7H9NO

IUPAC Name:

4-amino-m-cresol

Constituent 2

Reference substance name:

1-Hydroxy-3-methyl-4-aminobenzene

IUPAC Name:

1-Hydroxy-3-methyl-4-aminobenzene

Test material form:

solid: crystalline

Details on test material:

- Name of test material: 1-Hydroxy-3-methyl-4-aminobenzene
- TSIN: Not reported
- Substance type: Pure active substance
- Physical state: Beige, fine crystalline powder
- Stability under test conditions: Not reported
- Storage condition of test material: Not reported

Test animals

Species:

mouse

Strain:

CF-1

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Animals of SPF breed were obtained from Winkelmann Inc.
- Age at study initiation: Not reported
- Weight at study initiation: In the range of 21-32 g
- Fasting period before study: Animals were fasted for 16 hour prior to treatment.
- Housing: Animals were housed in a group of 5 animals each in Makrolon type III cages from Ebeco Inc., with standard bedding from Ssniff Inc.
- Diet: Standard laboratory diet from Altromin Inc, ad libitum.
- Water: Drinking water, ad libitum
- Acclimation period: Not reported

ENVIRONMENTAL CONDITIONS
- Temperature: 20±2°C
- Humidity: 50±5% (maximum deviation)
- Air changes: Approximately 15-fold air exchange per hour
- Photoperiod: Alternating light-dark periods of 12 hours each

IN-LIFE DATES: Not reported

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: suspended in 10% gum arabic

Details on oral exposure:

VEHICLE: No details on vehicle were provided in the study report.

MAXIMUM DOSE VOLUME APPLIED: Not reported

DOSAGE PREPARATION: The dosing formulation was prepared in 10% gum arabic
- Rationale for the selection of the starting dose: The doses were selected based on the results of preliminary study.

Doses:

750, 800, 850, 900, 950 and 1000 mg/kg bw

No. of animals per sex per dose:

6 females

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The body weights were determined on weekly basis.
- Necropsy of survivors performed: Yes, all animals were necropsised at the end of the experiment and during the experiment in the case of mortalities, respectively.
- Other examinations performed: The other observations were as follows:
a) Mortality: Daily
b) Clinical-toxicological observations: Daily

Statistics:

LD50 values were calculated by the method of Spearman-Kärber.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

908 mg/kg bw

Based on:

test mat.

95% CL:

743 - 1 073

Mortality:

- Deaths occurred within 2- 48 hours after substance administration.

For details on mortality, refer ‘Table 1’ provided in the section 'Any other information on results incl. tables'.

Clinical signs:

- In the treated animals, reduction of the physical activity was observed.

Body weight:

No detailed information on body weight was provided in the study report.

Gross pathology:

- At necropsy no macroscopic organ changes/damages were observed.

Any other information on results incl. tables

Preliminary study: A range finding study was performed to select the doses for main study, by using 6 female mice. The results of the preliminary experiment revealed that the median lethal dose (LD50) must be in the range between 0.5 and 1.5 g/kg. Respective dosage was extended in the main experiment to a larger number of animals for a more precise determination of the median lethal dose.

Table 1. Mortality after treatment with 1-Hydroxy-3-methyl-4-aminobenzene (study # 83525)

Dose (mg/kg bw)	Mortalities
750	0/6
800	1/6
850	3/6
900	1/6
950	3/6
1000	6/6

Applicant's summary and conclusion

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral toxicity (LD50) of 1-Hydroxy-3-methyl-4-aminobenzene when administered once orally to CF1 mouse was 908 mg/kg bw.

Executive summary:

The purpose of the study was to determine the acute oral toxicity (LD50) of 1-Hydroxy-3-methyl-4-aminobenzene after a single oral administration to mice.

CF1 female mice obtained from Winkelmann Inc. were used in the study. 6 animals were used in each treatment group. Animals were housed in groups of 6 animals in each Makrolon type III cage. Animals were housed in controlled environment (Temperature: 20±2°C, humidity: 50±5% (maximum deviation), air changes: approximately 15-fold air exchange per hour, photoperiod: Alternating light-dark periods of 12 hours each).

A range finding study was performed, to determine the doses for the main study, in the dose range of 0.5 to 1.5 g/kg bw. Based on the results of the range finding study, the following doses were selected for the main study.

750, 800, 850, 900, 950 and 1000 mg/kg bw

Mortality and clinical signs were observed daily during the 14-day observation period. All animals were submitted to a gross necropsy at the end of the observation period.

Deaths occurred within 2-48 hours after treatment. The mortalities observed in different dose groups were as follows:

0/6, 1/6, 3/6, 1/6, 3/6 and 6/6 at dose levels of 750, 800, 850, 900, 950 and 1000 mg/kg bw, respectively.

In the treated animals, reduction of physical activity was observed. At necropsy, no macroscopic organ changes/damages were observed.

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.