Benzophenone

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

Study period:

1993/2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

2000

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Deviations:

no

Principles of method if other than guideline:

Preliminary range-finding studies were performed. Factors affecting dose selection included chemical solubility and toxicity and the extent of cell cycle delay induced by benzophenone exposure; the limiting factor was toxicity.

GLP compliance:

not specified

Type of assay:

other: micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

Benzophenone

EC Number:

204-337-6

EC Name:

Benzophenone

Cas Number:

119-61-9

Molecular formula:

C13H10O

IUPAC Name:

diphenylmethanone

Details on test material:

Molecular weight 182.22
Boiling point 305.4° C
Flash point greater than 110° C
Vapor pressure 1 mm Hg at 108.2° C
Refractive index 1.60
Log octanol/water partition coefficient 3.18
Solubility Insoluble in water; soluble in organic solvents including alcohol, acetone, ether, acetic acid, chloroform, and benzene

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:

corn oil

Details on exposure:

Mice were injected intraperitoneally

Duration of treatment / exposure:

3 days

Frequency of treatment:

3 times with intervals of 24 hours

Post exposure period:

24 hours after last injection

Doses / concentrations

Remarks:

200, 300, 400 or 500 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Positive control(s):

25 mg/kg bw cyclophosphamide i.p.

Examinations

Tissues and cell types examined:

The mice were killed 24 hours after the last injection, and blood smears were prepared from bone marrow cells obtained from the femurs.

Details of tissue and slide preparation:

Airdried smears were fixed and stained; 2,000 polychromatic erythrocytes (PCEs) were scored for the frequency of micronucleated cells in each of five animals per dose group.

Evaluation criteria:

In the micronucleus test, an individual trial was considered positive if the trend test P value was less than or equal to 0.025 or if the P value for any single dose group was less than or equal to 0.025 divided by the number of dose groups. A final call of positive for micronucleus induction is preferably based on reproducibly positive trials (as noted above). Ultimately, the final call is determined by the scientific staff after considering the results of statistical analyses, the reproducibility of any effects observed, and the magnitudes of those effects.

Statistics:

The results were tabulated as the mean of the pooled results from all animals within a treatment group, plus or minus the standard error of the mean. The frequency of micronucleated cells among PCEs was analysed by a statistical software package that tested for increasing trend over dose groups using a one-tailed Cochran-Armitage trend test, followed by pairwise comparisons between each dosed group and the control group. In the presence of excess binomial variation, as detected by a binomial dispersion test, the binomial variance of the Cochran-Armitage test was adjusted upward in proportion to the excess variation.

Results and discussion

Test results

Key result

Sex:

male

Genotoxicity:

negative

Toxicity:

no effects

Vehicle controls validity:

valid

Negative controls validity:

not specified

Positive controls validity:

valid

Applicant's summary and conclusion

Conclusions:

Benzophenone did not induce micronuclei in any of the doses tested and is therefore considered nonmutagenic in this test system.

Executive summary:

Benzophenone was tested in an in vivo micronucleus test according to a standard three-exposure protocol. Male B6C3F1 mice were injected intraperitoneally three times at 24-hour intervals with benzophenone dissolved in corn oil; the total dosing volume was 0.4 mL, the doses were 200, 300, 400 and 500 mg/kg bw per injection. Solvent control mice were injected with 0.4 mL of corn oil only. The positive control mice received injections of 25 mg cyclophosphamide/kg. The mice were killed 24 hours after the last injection, and blood smears were prepared from bone marrow cells obtained from the femurs. Air-dried smears were fixed and stained and 2000 polychromatic erythrocytes (PCEs) were scored for the frequency of micronucleated cells in each of five animals per dose group. In contrast to the positive control, benzophenone did not increase the number of micronucleated polychromatic erythrocytes and did therefore not induce chromosomal damage.