2-tert-butylhydroquinone

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: gene mutation

Remarks:

Micronucleus study

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 NTP report

Data source

Reference

Reference Type:

publication

Title:

Gene mutation in vivo toxcity study of the test chemical

Author:

DHHS

Year:

1997

Bibliographic source:

NTP

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Refer below principle

Principles of method if other than guideline:

Mouse bone marrow micronucleus test was performed to determine the mutagenic nature of the test chemical

GLP compliance:

not specified

Type of assay:

other: Micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

2-tert-butylhydroquinone

EC Number:

217-752-2

EC Name:

2-tert-butylhydroquinone

Cas Number:

1948-33-0

Molecular formula:

C10-H14-O2

IUPAC Name:

2-tert-butylbenzene-1,4-diol

Details on test material:

- Name of test material: tert-Butyl hydroquinone (TBHQ)
- IUPAC name: 2-tert-Butylhydroquinone
- Molecular formula: C10H14O2
- Molecular weight: 166.219 g/mol
- Substance type: Organic
- Physical state: No data
- Purity: No data
- Impurities (identity and concentrations): No data

Test animals

Species:

mouse

Strain:

B6C3F1

Sex:

male

Details on test animals or test system and environmental conditions:

No data

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

- Vehicle(s)/solvent(s) used: Corn oil
- Justification for choice of solvent/vehicle: The test chemical was soluble in corn oil
- Concentration of test material in vehicle: 0, 9.38, 18.75, 37.50, 75.00, 150.00, 300.00 mg/Kg
- Amount of vehicle (if gavage or dermal): 10 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:

72 hrs

Frequency of treatment:

Thrice at 24 hrs interval

Post exposure period:

No data

Doses / concentrations

Remarks:

0, 9.38, 18.75, 37.50, 75.00, 150.00, or 300.00 mg/Kg

No. of animals per sex per dose:

5 mice/ dose

Control animals:

yes, concurrent vehicle

Positive control(s):

Cyclophosphamide
- Justification for choice of positive control(s): No data
- Route of administration: Intraperitoneally
- Doses / concentrations: 25 mg/Kg

Examinations

Tissues and cell types examined:

Bone marrow smears obtained from femurs

Details of tissue and slide preparation:

CRITERIA FOR DOSE SELECTION: No data

TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields): Male B6C3F1 mice received three intraperitoneal injections of the test chemical dissolved in com oil at 24-hour intervals. Up to five mice were treated per exposure group and the highest dose administered was 400 mg/kg. Solvent control animals received com oil only, and the positive control mice received injections of 25 mg/kg cyclophosphamide. The mice were killed 24 hours after the final injection and slides were prepared from bone marrow smears obtained from the femurs.

DETAILS OF SLIDE PREPARATION: Slides were air-dried, fixed, and stained.

METHOD OF ANALYSIS: Two thousand polychromatic erythrocytes (PCEs) were scored per animal for frequency of micronucleated cells.

OTHER: Selection of doses was based upon published LD50 information; no preliminary range-finding studies were required.

Evaluation criteria:

No data

Statistics:

The mean of the pooled results from all animals within an exposure group, plus or minus the standard error of the mean. The frequency of micronucleated cells among PCEs was analyzed by a statistical software package that tested for increasing trend over exposure groups using a one-tailed Cochran-Armitage trend test, followed by pairwise comparisons between each exposure group and the control group. In the presence of excess binomial variation, as detected by a
lbinomial dispersion test, the binomial variance of the Cochran-Armitage test was adjusted upward in lproportion to the excess variation. In the micronucleus test, an individual trial is considered positive if the trend test P value is ≤0.025 or the P valuefor any single exposure group is ~0.025/n where n = the number of exposure groups. A final call of positive for micronucleus induction is preferably based on reproducibly positive trials.

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Toxicity:

not specified

Vehicle controls validity:

valid

Negative controls validity:

not specified

Positive controls validity:

valid

Additional information on results:

No data

Any other information on results incl. tables

Table: Mutagenic potential of the test chemical

Dose	No. of mice	Micronucleated PCEs/ 1000 cells
CPA 25.00	5	17.6±1.46
Test chemical
0	5	0.8±0.44
9.38	4	0.9±0.43
18.75	5	1.7±0.46
37.50	5	1.3±0.41
75.00	5	1.0±0.45
150.00	5	1.4±0.19
300.00	1	1.0

Applicant's summary and conclusion

Conclusions:

The test chemical did not induce micronuclei formation in bone marrow smears of B6C3F1 mice.

Executive summary:

In vivo micronucleus assay was performed to determine the mutagenic nature of the test chemical. The study was performed using male B6C3F1 mice. Male B6C3F1 mice received three intraperitoneal injections of the test chemical dissolved in com oil at 24-hour intervals. Up to five mice were treated per exposure group and the highest dose administered was 400 mg/kg. Solvent control animals received com oil only, and the positive control mice received injections of 25 mg/kg cyclophosphamide. The mice were killed 24 hours after the final injection and slides were prepared from bone marrow smears obtained from the femurs. Slides were air-dried, fixed, and stained. Two thousand polychromatic erythrocytes (PCEs) were scored per animal for frequency of micronucleated cells. No animals survived in the 400 mg/kg group and only one mouse survived in the 300 mg/kg dose group. Based on the observations made, the test chemical did not induce micronuclei formation in bone marrow smears of B6C3F1 mice.