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Toxicological information

Genetic toxicity: in vivo

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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:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
2000

Materials and methods

Test guideline
Qualifier:
according to
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

Reference
Name:
Unnamed
Type:
Constituent
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 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.