p-hydroxyphenylacetic acid

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:

Mutagens from roasted seeds of Moringa oleifera

Author:

Irene M. Villasenor , Clara Y. Lim-Sylianco and Fabian Dayrit

Year:

1989

Bibliographic source:

Mutation Research, 224 (1989) 209-212

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Refre below principle

Principles of method if other than guideline:

In vivo micronucleus test was performed to determine the mutagenic nature of 4-Hydroxyphenylacetic Acid

GLP compliance:

not specified

Type of assay:

other: In vivo micronucleus test

Test material

Test material information

Constituent 1

Reference substance name:

4-Hydroxyphenylacetic Acid

Cas Number:

156-38-7

Molecular formula:

C8H8O3

IUPAC Name:

4-Hydroxyphenylacetic Acid

Details on test material:

- Name of test material: 4-Hydroxyphenylacetic Acid
- IUPAC name: 4-Hydroxyphenylacetic Acid
- Molecular formula: C8H8O3
- Molecular weight: 152.148 g/mol
- Substance type: Organic

Specific details on test material used for the study:

- Name of test material: 4-Hydroxyphenylacetic Acid
- IUPAC name: 4-Hydroxyphenylacetic Acid
- Molecular formula: C8H8O3
- Molecular weight: 152.148 g/mol
- Substance type: Organic
- Physical state: No data
- Purity: No data
- Impurities (identity and concentrations): No data

Test animals

Species:

mouse

Strain:

Swiss Webster

Remarks:

Albino

Details on species / strain selection:

No data

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: No data
- Age at study initiation: 7-12 weeks old
- Weight at study initiation: No data
- Assigned to test groups randomly: [no/yes, under following basis: ] No data
- 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: No data

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:

intraperitoneal

Vehicle:

- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: The test chemical was soluble in DMSO
- Concentration of test material in vehicle: 8.0 mL/Kg
- Amount of vehicle (if gavage or dermal): 8.0 mL/Kg
- Type and concentration of dispersant aid (if powder): No data
- Lot/batch no. (if required): No data
- Purity: No data

Details on exposure:

No data

Duration of treatment / exposure:

48 hrs

Frequency of treatment:

Two doses, 24 h apart

Post exposure period:

No data

Doses / concentrations

Remarks:

0 or 47 mg/Kg

No. of animals per sex per dose:

Total: 10
0 mg/Kg: 5 mice
47 mg/Kg: 5 mice

Control animals:

yes, concurrent vehicle

Positive control(s):

No data

Examinations

Tissues and cell types examined:

Femoral tissue were examined

Details of tissue and slide preparation:

CRITERIA FOR DOSE SELECTION: No data

TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields): Two doses (47 mg/Kg) of the test chemical, 24 h apart, were administered intraperitoneally to Swiss Webster albino mice. Six hours after the second administration, the mice were killed by dislocation of the neck. Both femora were removed by cutting through the pelvis and tibia. After removal of the muscle tissues, the distal epiphyseal portion was torn off. The proximal end of the femur was shortened carefully with scissors until a small opening to the marrow canal was seen. About 0.2 ml of fetal calf serum was introduced into a 1-ml syringe and then the hypodermic needle was inserted a few mm into the proximal end of the marrow. The femur was then submerged completely in 2 ml serum in a 5-ml test tube and the marrow was aspirated. After flushing and aspirating several times, the test tube was centrifuged at 1000 rpm for 5 rain and the supernatant was decanted. The cells in the sediment were mixed carefully using a Pasteur pipette and aspirator and were then smeared on glass slides. The 3 slides prepared for each mouse were left overnight to dry.

DETAILS OF SLIDE PREPARATION: The following procedure was used in staining the slides: 3 min in undiluted May-Grunwald stain; 2 rain in 50% May-Grunwald stain solution diluted with distilled water; and 10 rain in 15% aqueous Giemsa stain solution.

METHOD OF ANALYSIS: No data

OTHER: No data

Evaluation criteria:

The number of micronucleated polychromatic erythrocytes (MN-PCE) per 1000 polychromatic erythrocytes (PCE) was counted

Statistics:

Mean ± SD

Results and discussion

Test results

Sex:

not specified

Genotoxicity:

negative

Toxicity:

not specified

Vehicle controls validity:

valid

Negative controls validity:

not specified

Positive controls validity:

valid

Remarks on result:

other: No mutagenic potential

Additional information on results:

No data

Any other information on results incl. tables

Table: Results of the micronucleus study

Compound	Dose (mg/Kg)	Number of MN-PCE/1000 PCE^a (mg/kg) (mean±SD)
4-Hydroxyphenylacetic Acid	47	3.53±0.81
DMSO	8.0 mL/Kg	2.52±0.62

 

Applicant's summary and conclusion

Conclusions:

4-Hydroxyphenylacetic Acid did not induce micronuclei production in the femora of mice in vivo and hence it not likely to classify as a gene mutant in vivo.

Executive summary:

In vivo micronucleus test was performed to determine the mutagenic nature of 4-Hydroxyphenylacetic Acid. The study was performed using Swiss Webster albino mice. The test chemical was dissolved in DMSO and used at dose level of 0 or 47 mg/Kg. 5 mice were used for each dose level. Concurrent solvent and positive control chemicals were also included in the study.Two doses (47 mg/Kg) of the test chemical, 24 h apart, were administered intraperitoneally to Swiss Webster albino mice. Six hours after the second administration, the mice were killed by dislocation of the neck. Both femora were removed by cutting through the pelvis and tibia. After removal of the muscle tissues, the distal epiphyseal portion was torn off. The proximal end of the femur was shortened carefully with scissors until a small opening to the marrow canal was seen. About 0.2 ml of fetal calf serum was introduced into a 1-ml syringe and then the hypodermic needle was inserted a few mm into the proximal end of the marrow. The femur was then submerged completely in 2 ml serum in a 5-ml test tube and the marrow was aspirated. After flushing and aspirating several times, the test tube was centrifuged at 1000 rpm for 5 rain and the supernatant was decanted. The cells in the sediment were mixed carefully using a Pasteur pipette and aspirator and were then smeared on glass slides. The 3 slides prepared for each mouse were left overnight to dry. The following procedure was used in staining the slides: 3 min in undiluted May-Grunwald stain; 2 rain in 50% May-Grunwald stain solution diluted with distilled water; and 10 rain in 15% aqueous Giemsa stain solution.The number of micronucleated polychromatic erythrocytes (MN-PCE) per 1000 polychromatic erythrocytes (PCE) was counted. 4-Hydroxyphenylacetic Acid did not induce micronuclei production in the femora of mice in vivo and hence it not likely to classify as a gene mutant in vivo.