Tetrachloroethylene

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: non-GLP, non-guideline study, published data, some restrictions, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

The induction of micronuclei in mice hepatocytes and recticulocytes by tetrachloroethylene.

Author:

Murakami, K. and Horikawa, K.

Year:

1995

Bibliographic source:

Chemosphere 31 (7); 3733-3739.

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:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

Tetrachloroethylene

EC Number:

204-825-9

EC Name:

Tetrachloroethylene

Cas Number:

127-18-4

Molecular formula:

C2Cl4

IUPAC Name:

tetrachloroethene

Details on test material:

Name of test material (as cited in study report): Tetra Source: Merck, Frankfurt, GermanyPurity: 99.8 %The substance was analyzed by gas chromatography and mass spectrometry (GC-MS) to check for epichlorohydrin, chloroform, and carbon tetrachloride, but these contaminants were absent.

Test animals

Species:

mouse

Strain:

other: ddY

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS- Source: Seiwa Experimental Animal Inc., Fukuoka Japan- Age at study initiation: 7 weeks- Housing: steel cages with wood chips for bedding- Diet: ad libitum- Water: ad libitum- Acclimation period: 1 weekENVIRONMENTAL CONDITIONS- Temperature (°C): 22 ± 2- Humidity (%): no data- Air changes (per hr): no data- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

- Vehicle(s)/solvent(s) used: olive oil (Wako Pure Chemical Industries, Ltd, Osaka, Japan)- Amount of vehicle: 0.5 ml

Duration of treatment / exposure:

i.p. injection of 0.5 ml tetra in olive oil

Frequency of treatment:

once

Post exposure period:

up to 72 h after administration

Doses / concentrations

Remarks:

Doses / Concentrations:500, 1000, 2000 mg/kg body weightBasis:nominal conc.

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Positive control(s):

Mitomycin C (MMC, Kyowa Hakko Kogyo Co., Ltd., Tokyo, Japan). MMC was administered once at a dose of 1.0 mg / kg as the positive reference chemical.

Examinations

Tissues and cell types examined:

From each of 5 mice in a group, 5 μl of blood was collected from the tail without any anticoagulant at 0, 24, 48 and 72 h after administration.Peripheral blood cells were stained using acridine orange coated slides. One thousand reticulocytes were analyzed per animal, and the numbers of micronucleated reticulocytes were recorded.

Evaluation criteria:

not reported

Statistics:

not reported

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Toxicity:

not specified

Vehicle controls validity:

valid

Negative controls validity:

not valid

Positive controls validity:

valid

Additional information on results:

The level of micronucleus induction between tetra treated- and untreated- mice was the same at doses of 500 to 2000 mg per kg, in samples of mouse peripheral blood at 0, 24, 48 and 72 h after injection. These results showed that the substance dose not induce micronuclei in mouse peripheral blood reticulocytes.

Any other information on results incl. tables

Although exposure was up to a limit dose of 2000 mg/kg by the i.p. route and shown to cause systemic toxicity (i.p. mouse LD₅₀=4600 mg/kg), cytotoxicity was not observed, which demonstrates that sufficient exposure of target cells did not occur.