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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
(partly limited documentation, e.g. no details about test substance or no tabulated details on results; no data on cytotoxicity in bone marrow; only 50 cells per rat analysed [100 cells recommended]; MTD presumably not reached)

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1980
Report Date:
1980

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)
Deviations:
yes
Remarks:
(only 50 metaphases scored)
GLP compliance:
not specified
Type of assay:
chromosome aberration assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Specific details on test material used for the study:
- Name of test material: dimethylacetamide (DMAC)
No details available.

Test animals

Species:
rat
Strain:
other: CD
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Diet and water ad libitum but not during exposure.
- Some evidence for sialodacryoadenitis (SDA Virus; natural occurring pathogen in rats) in all rats.
- Housing: males caged individually

no further details available

Administration / exposure

Route of administration:
inhalation
Vehicle:
see details of exposure
Details on exposure:
Whole body exposure; generation by bubbling nitrogen through DMAC contained in a glass gas washing bottle (50 °C); vapour mixture diluted with filtered, compressed air; atmospheres in the exposure chambers were dynamic (continuously generated for a single pass through the animal holding zone); concentrations within the exposure chambers maintained by regulating the flow of nitrogen and diluting air into the mixing vessels.

Continuously monitoring in the breathing zone by infra-red gas analysers; calibrations performed.

Chamber relative humidity and temperature was measured every hour.

After exposure rats observed for clinical signs, ear numbers checked, body weights recorded and returned to their cages.
Duration of treatment / exposure:
7 h
Frequency of treatment:
once or for five days
Post exposure period:
Three different sampling times: 6, 24 or 48 h after the last exposure rats were sacrificed; 2 h prior to sacrifice were i.p. injected with 3 mg/kg bw colchicine.
Doses / concentrationsopen allclose all
Dose / conc.:
20 ppm (nominal)
Remarks:
70 mg/m³
analytical data revealed deviations from the target concentrations of more than +-10% were limited to 20 min high (20 ppm target concentration) and 40 min low, 30 min high (700 ppm target concentration); no further details
Dose / conc.:
700 ppm (nominal)
Remarks:
2500 mg/m³
analytical data revealed deviations from the target concentrations of more than +-10% were limited to 20 min high (20 ppm target concentration) and 40 min low, 30 min high (700 ppm target concentration); no further details
No. of animals per sex per dose:
no details available
Control animals:
yes, concurrent vehicle
Positive control(s):
Yes, single gavage with 250 mg/kg bw ethyl methanesulfonate.

Examinations

Tissues and cell types examined:
Bone marrow cells; investigated abnormalities: gaps, breaks, fragments, dicentrics, translocations (within the limitations of the staining methods), and pulverisation
Details of tissue and slide preparation:
Bone marrow cell suspension prepared, fixed and dried on slides and examined by light microscopical methods after staining with Giemsa R66.
50 cells with well-spread chromosomes per animal examined on a blind basis.
Evaluation criteria:
Statistical significance (a) including all chromosomal abnormalities and (b) excluding cells only exhibiting gaps.
Statistics:
The data were transformed using the Freeman-Tukey transformation.
A one-sided Student's t test was used on the transformed values.

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
no effects
Vehicle controls validity:
valid
Positive controls validity:
valid
Additional information on results:
Significant effects in positive controls (breaks with fragments, exchanges and multiple aberrations), especially after the post exposure period of 48 h. No increase in the incidences of chromosomal aberrations in the treatment groups.

Any other information on results incl. tables

Data on acute inhalation toxicity in Section 7.2.3 suggested no toxic effects at a dose level of 700 ppm.

Applicant's summary and conclusion

Conclusions:
No clastogenic activity was detected in the bone marrow of rats after inhalation exposure to 700 ppm (2500 mg/m³).
Executive summary:

The Tier II mutagenic screening of the test substance was conducted according to OECD 475 in 1980. GLP compliance was not specified. A cytogenetic analysis of rat bone marrow cells was performed after in vivo exposure to 20 or 700 ppm of the test substance for seven hours per day for 1 or 5 days in male and female rats. A positive (single gavage with 250 mg/kg bw ethyl methanesulfonate) control and a negative control was included. Sampling times were 6 h, 24 h, and 48 h post-exposure. The frequencies of chromosomal aberrations were not increased significantly in the rat bone marrow cells.