Tetrachlorophthalic anhydride

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian germ cell study: cytogenicity / chromosome aberration

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Meets generally accepted scientific standards and acceptable for assessment.

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Toxicity studies of tetrachlorophthalic anhydride (CAS No. 117-08-8) administered by gavage to F344/N Rats and B6C3F1 Mice.

Author:

NTP

Year:

1993

Bibliographic source:

NTP Technical Report Series No 28.

Reference 2

Reference Type:

publication

Title:

In vivo cytogenetic activity of diphenylhydantoin in mice.

Author:

McFee AF, Tice RR and Shelby MD

Year:

1992

Bibliographic source:

Mutation Research, 278, 61-68

Materials and methods

Principles of method if other than guideline:

Chromosomal aberration (CA) was determined in male B6C3F1 mice (10-16 weeks old) in cells of the bone marrow after a single intraperitoneal injection of the test substance. Injection of the test substance was performed one hour after subcutaneous implantation of a bromodeoxyuridine tablet in groups of 8/dose group. All animals received a single injection of 25 μg cochicine/animal two hours prior to sacrifice.

GLP compliance:

not specified

Type of assay:

chromosome aberration assay

Test material

Test material information

Constituent 1

Reference substance name:

Tetrachlorophthalic anhydride

EC Number:

204-171-4

EC Name:

Tetrachlorophthalic anhydride

Cas Number:

117-08-8

Molecular formula:

C8Cl4O3

IUPAC Name:

tetrachloro-1,3-dihydro-2-benzofuran-1,3-dione

Details on test material:

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

Test animals

Species:

mouse

Strain:

B6C3F1

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 10-16 weeks old

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

- Vehicle(s)/solvent(s) used: DMSO

Duration of treatment / exposure:

single application

Frequency of treatment:

once

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 100, 200, 400 mg/kg bw
Basis:

No. of animals per sex per dose:

8

Control animals:

yes, concurrent vehicle

Positive control(s):

Dimethylbenzanthracene
- Route of administration: intraperitoneal
- Doses / concentrations: 200 mg/kg bw in DMSO

Examinations

Tissues and cell types examined:

bone marrow

Details of tissue and slide preparation:

DETAILS OF SLIDE PREPARATION: The harvest time was 17 hours after application of the test substance. Bone marrow cells were flushed from a femur with phosphate-buffered saline, prepared for examination of metaphase and stained.


METHOD OF ANALYSIS: 50 selected first-division metaphases were scored from each of 8 animals per treatment group. Responses were evaluated as the percentage of aberrant metaphases cells, excluding gaps.

Evaluation criteria:

A dose-related increase in the relative number of cells with chromosome aberrations or a clear increase in the number of cells with aberrations in a single dose group at a single sampling time.

Statistics:

Significance was tested by the one-tailed trend test.

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Toxicity:

no effects

Vehicle controls validity:

valid

Positive controls validity:

valid

Any other information on results incl. tables

Test substance	Dose (mg/kg bw)	No. of animals	Percent Cells w/ Aberrations (Mean ± SEM)	Pairwise P
DMSO	0	8	2.00 ± 1.25
Tetrachlorophthalic anhydride	100	8	0.50 ± 0.33	0.9719
	200	8	1.25 ± 0.65	0.7992
	400	8	1.25 ± 0.53	0.7992
Dimethylbenzanthracene	200	8	18.75 ± 3.21	0.0000