Chloroacetonitrile

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1995

Materials and methods

Principles of method if other than guideline:

The assay was performed as described by Jaylet et al. (1986) and according to the recommendations of the French standard AFNOR T-90-325 (AFNOR, 1987) revised in 1992 (AFNOR, 1992).
Briefly, larvae at stage 53 of the developmental table established by Gallien and Durocher (1957) were used for the experiment, since at this stage the mitotic index is at a maximum (Deparis, 1973). The highest concentration to be used in the 12-day micronucleus assay is defined as half the minimum concentration that led to detectable physiological disturbances (weight loss, swelling, reduction in food intake, swimming in circles, etc.) in a 6-day preliminary toxicity test. In every glass container, the water (containing the dissolved chemical at the required concentration) was renewed daily. After 12 days of treatment, blood samples were taken from every animal (15-20 larvae per concentration) by cardiac puncture into an heparinized micropipette. The slides (one for each animal) were stained with Masson acid Hemalun and the number of micronucleated erythocytes was counted in a sample of 1000 erythrocytes.

GLP compliance:

not specified

Type of assay:

other: Newt micronucleus test

Test material

Test material information

Constituent 1

Reference substance name:

Chloroacetonitrile

EC Number:

203-467-0

EC Name:

Chloroacetonitrile

Cas Number:

107-14-2

Molecular formula:

C2H2ClN

IUPAC Name:

2-chloroacetonitrile

Test material form:

liquid

Test animals

Species:

other: Pleurodeles waltl larvae

Sex:

not specified

Details on test animals or test system and environmental conditions:

Test organisms were provided by the Centre de Biologie du Développement, University P. Sabatier (Toulouse, France) and acclimatized for one week before the experiment.

Administration / exposure

Route of administration:

other: test organisms in water containing the test substance

Vehicle:

water (containing the dissolved chemical at the required concentration)

Duration of treatment / exposure:

12 days

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

1.25 other: µg/ml

Doses / concentrations 2

Dose / conc.:

2.5 other: µg/ml

Doses / concentrations 3

Dose / conc.:

5 other: µg/ml

No. of animals per sex per dose:

15-20 larvae per concentration

Examinations

Tissues and cell types examined:

Blood, erythrocytes

Details of tissue and slide preparation:

Blood samples were taken from every animal by cardiac puncture into an heparinized micropipette. The slides were stained with Masson acid Hemalun and the number of micronucleated erythocytes was counted in a sample of 1000 erythrocytes.

Evaluation criteria:

A compound is considered as genotoxic if:
(1) it induces a statistically significant increase in the number of micronucleated erythrocytes compared to the control (p < 0.05) and
(2) the median for the treated group is at least twice as high as the control median.
In case the second condition is not fulfilled, the chemical is considered as weakly genotoxic.

Statistics:

As there is not a normal distribution of micronucleus frequencies, median values and quartiles were calculated instead of mean values. The statistical method of Mac Gill et al. (1978), a quick and reliable test adapted to small sample sizes and values that do not have normal distribution, was used to analyse the results.

Results and discussion

Test results

Sex:

not specified

Genotoxicity:

positive

Remarks:

1.25-2.5 (clastogenic effects)

Toxicity:

yes

Remarks:

10 µg/ml