3-aminophenol

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data is from peer reviewed publication

Data source

Reference

Reference Type:

publication

Title:

Gene mutation toxicity in vivo study for the test chemical

Author:

Hossack and Richardson

Year:

1977

Bibliographic source:

Experentia

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Refer below principle

Principles of method if other than guideline:

In vivo mammalian somatic cell study was performed to determine the mutagenic nature of the test chemical

GLP compliance:

not specified

Type of assay:

other: In vivo mammalian somatic cell study: Micronucleus study

Test material

Test material information

Constituent 1

Reference substance name:

3-aminophenol

EC Number:

209-711-2

EC Name:

3-aminophenol

Cas Number:

591-27-5

Molecular formula:

C6H7NO

IUPAC Name:

3-aminophenol

Details on test material:

- Name of test material: 3-aminophenol
- Molecular formula: C6H6NO
- Molecular weight: 109.127 g/mol
- Substance type: Organic
- Physical state: No data
- Purity: No data
- Impurities (identity and concentrations): No data

Test animals

Species:

rat

Strain:

Sprague-Dawley

Remarks:

CFY - descendants

Details on species / strain selection:

No data

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Anglia Laboratory Animals, Alconbury, Cambs., U.K.
- Age at study initiation: No data
- Weight at study initiation: 130-160 g
- Assigned to test groups randomly: Random allocation
- Fasting period before study: No data
- Housing: No data
- Diet (e.g. ad libitum): No data
- Water (e.g. ad libitum): No data
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data
- Humidity (%): No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): No data

IN-LIFE DATES: From: To: No data

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

- Vehicle(s)/solvent(s) used: The test chemical was prepared as suspensions in 0.5% (w/v) gum tragacanth containing 0.05% (w/v) sodium sulphite to give a dose range of 0 or 5000 mg/Kg.
- Justification for choice of solvent/vehicle: The test chemical was soluble in the solvent
- Concentration of test material in vehicle: 0 or 5000 mg/Kg
- Amount of vehicle (if gavage or dermal): No data
- Type and concentration of dispersant aid (if powder): No data
- Lot/batch no. (if required): No data
- Purity: No data

Details on exposure:

For oral route
PREPARATION OF DOSING SOLUTIONS: The test chemical was prepared as suspensions in 0.5% (w/v) gum tragacanth containing 0.05% (w/v) sodium sulphite to give a dose range of 0 or 5000 mg/Kg.

DIET PREPARATION
- Rate of preparation of diet (frequency): No data
- Mixing appropriate amounts with (Type of food): No data
- Storage temperature of food: No data

Duration of treatment / exposure:

24 hrs

Frequency of treatment:

Twice separated by an interval of 24 h

Post exposure period:

No data

Doses / concentrations

Remarks:

0 or 5000 mg/Kg

No. of animals per sex per dose:

Total: 10 males and 10 females
0 mg/Kg: 5 males and 5 females
5000 mg/Kg: 5 males and 5 females

Control animals:

yes, concurrent vehicle

Positive control(s):

No data

Examinations

Tissues and cell types examined:

Bone marrow

Details of tissue and slide preparation:

CRITERIA FOR DOSE SELECTION: The doses were selected on the basis of preliminary dose range finding study

TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields): 6 h after the 2nd dose the animals were killed by the i.p.injection of pentobarbitone sodium (Expiral) the femurs dissected out and bone-marrow smears prepared.

DETAILS OF SLIDE PREPARATION: The smears were fixed in methanol, defatted in xylene and stained with Giemsa stain.

METHOD OF ANALYSIS: The stained smears were then examined microscopically to determine the incidence of micronucleated cells per 2000 polychromatic erythrocytes per animal. The group mean counts and ranges were then compared with the values obtained with the vehicle control group and with laboratory standard values.

OTHER: No data

Evaluation criteria:

The group means counts and ranges of of micronucleated cells were compared with the values obtained with the vehicle control group and with laboratory standard values.

Statistics:

No data

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

not specified

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

not specified

Remarks on result:

other: No mutagenic potential

Additional information on results:

RESULTS OF RANGE-FINDING STUDY
- Dose range: The total dosages given were determined in preliminary studies to be close to the lethal doses
- Solubility: No data
- Clinical signs of toxicity in test animals: No data
- Evidence of cytotoxicity in tissue analyzed: No data
- Rationale for exposure: No data
- Harvest times: No data
- High dose with and without activation: No data
- Other: No data

RESULTS OF DEFINITIVE STUDY
- Types of structural aberrations for significant dose levels (for Cytogenetic or SCE assay): No data
- Induction of micronuclei (for Micronucleus assay): No data
- Ratio of PCE/NCE (for Micronucleus assay): No data
- Appropriateness of dose levels and route: No data
- Statistical evaluation: No data

Other: Agitation and/or convulsions, and/or lethargy were observed in the treated animals. Orange urine was also seen in treated animals.

Any other information on results incl. tables

Table:

Chemical	Dose over 24 hrs (mg/Kg)	Mortality	Incidence of micronucleated cells per 2000 polychromatic erythroeytes per rat
			Mean	Range
Vehicle control	-	0	1.8	0-5
Test chemical	5000	3	1.9	0-4

 

Table 2. Rat micronucleus test Laboratory standard values for negative control groups

Total number of animals examined	Mean micronucleated cell count	Range of group mean counts	Range of individual counts
175	1.19	0.7-2.3	0-6

 

Applicant's summary and conclusion

Conclusions:

The test chemical did not induce micronuclei formation in the bone marrow of male and female rats.

Executive summary:

In vivo mammalian somatic cell study was performed to determine the mutagenic nature of the test chemical. The study was performed using male and female CFY strain rats. The test chemical was prepared as suspensions in 0.5% (w/v) gum tragacanth containing 0.05% (w/v) sodium sulphite to give a dose range of 0 or 5000 mg/Kg. The total dosages given were determined in preliminary studies to be close to the lethal doses, and were administered by gastric intubation as 2 equal doses separated by an interval of 24 h. 6 h after the 2nd dose the animals were killed by the i.p. injection of pentobarbitone sodium (Expiral) the femurs dissected out and bone-marrow smears prepared. The smears were fixed in methanol, defatted in xylene and stained with Giemsa stain. The stained smears were then examined microscopically to determine the incidence of micronucleated cells per 2000 polychromatic erythrocytes per animal. The group mean counts and ranges were then compared with the values obtained with the vehicle control group and with laboratory standard values.Agitation and/or convulsions, and/or lethargy were observed in the treated animals. Orange urine was also seen in treated animals.Based on the observations made,the test chemical did not induce micronuclei formation in the bone marrow of male and female rats.