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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
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:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
GLP compliance:
not specified
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
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 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.

Applicant's summary and conclusion