Benzophenone

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Study period:

July 12, 1992

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: A standard NTP (National Toxicology Program) protocol. Equivalent to OECD 474. No data on GLP.

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Unnamed

Year:

1992

Reference 2

Reference Type:

publication

Title:

Unnamed

Year:

2000

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

GLP compliance:

not specified

Type of assay:

chromosome aberration 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:

benzophenone

Details on test material:

- Name of test material (as cited in study report): Benzophenone

Test animals

Species:

mouse

Strain:

B6C3F1

Sex:

male

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

- Vehicle(s)/solvent(s) used: corn oil

Details on exposure:

Total dosing volume was 0.4 mL

Duration of treatment / exposure:

72 hours

Frequency of treatment:

3 treatments, 24 hours intervals

Doses / concentrations

Remarks:

Doses / Concentrations:
200, 300, 400, 500 mg/kg bw
Basis:
nominal conc.

No. of animals per sex per dose:

5 male mice per dose

Control animals:

yes, concurrent vehicle

Positive control(s):

Cyclophosphamide
- Route of administration: intraperitoneal
- Doses / concentrations: 25 mg/kg bw

Examinations

Tissues and cell types examined:

Tissue: Bone marrow
Cells: Erythrocytes

Details of tissue and slide preparation:

Mice were exposed to the chemical 3 times at 24 hour intervals by intraperitoneal injection. After 72 hours, the animals are euthanized by CO2 inhalation and the femurs are removed. Samples were collected 3.72 hours after the last dose. The bone marrow was flushed from the femurs and spread onto slides. The slides are air-dried, fixed, and stained with a fluorescent DNA-specific stain that easily illuminates any micronuclei that may be present. 2000 polychromatic erythrocytes (PCEs, reticulocytes; immature erythrocytes) are scored per animal for frequency of micronucleated cells in each of 5 animals per dose group. In addition, the percentage of PCEs among the total erythrocyte population in the bone marrow is scored for each dose group as an indicator of chemical-induced toxicity.

Evaluation criteria:

A positive trend test is one in which the P value is equal to or less than 0.025.

Statistics:

A trend test was performed to determine if there was an overall increase across all doses in the frequency of cells containing micronuclei, and a pairwise comparison of each dose group to the corresponding control, to see if any one dose group was statistically different from the control group in frequency of micronucleated cells. Data were presented as the mean number of micronucleated cells per 1,000 cells for each treatment group. A positive trend test is one in which the P value is equal to or less than 0.025.

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Toxicity:

not specified

Vehicle controls validity:

valid

Positive controls validity:

valid

Any other information on results incl. tables

Genetic toxicity evaluation of benzophenone in Micronucleous Study A27713 on B6C3F1 Mice.

Start Date	Sample Collection Time	Sex	Cell	Methodology Used	Dosing Regimen	Route	Trend Test P-Value
12/07/1992	24 Hours	Male	PCE	Slide Scoring	IP/IJ x 3, 72 Hours	Intraperitoneal Injection	0.085
				Dose (mg/kg)	Number of Animals Scored	Mean MN-PCE/1000 PCE ± SEM	Pairwise P
Vehicle Control	Corn Oil			0	5	1.20 ± 0.41
Test Chemical	Benzophenone			200	5	1.50 ± 0.32	0.2817
				300	5	1.50 ± 0.45	0.2817
				400	5	2.20 ± 0.72	0.0430
				500	5	1.70 ± 0.37	0.1764
Positive Control	Cyclophosphamide			25	5	22.40 ± 1.85	< 0.0001

Result: Negative

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative
An in-vivo micronucleous study performed with benzophenone was determined to be negative under test conditions.

Executive summary:

An in-vivo micronucleous assay was performed with benzophenone in male mice. Mice were exposed to 0 (control), 200, 300, 400 and 500 mg/kg bw 3 times at 24 hour intervals by intraperitoneal injection. Samples were collected 3.72 hours after the last dose. The animals were euthanized by CO2 inhalation and the femurs are removed. The bone marrow was flushed from the femurs and spread onto slides. 2000 polychromatic erythrocytes (PCEs, reticulocytes; immature erythrocytes) were scored per animal for frequency of micronucleated cells in each of 5 animals per dose group. Compared with the negative control, no effects were observed in polychromatic erythrocytes under test condtions. Therefore, benzophenone was determined to be negative for in-vivo cytogenicity.