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Diss Factsheets

Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
genetic toxicity in vitro, other
Remarks:
Type of genotoxicity: genome mutation in fungi
Type of information:
experimental study
Adequacy of study:
weight of evidence
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:
A comparative study on ethanol and acetaldehyde as inducers of chromosome malsegregation in Aspergillus nidulans.
Author:
Crebelli, R. et al.
Year:
1989
Bibliographic source:
Mutat Res 215: 187-195

Materials and methods

Principles of method if other than guideline:
Determination of chromosomal malsegregation in ascomycetes during mitosis induced by test substance application.
GLP compliance:
not specified
Type of assay:
other: Mitotic recombination in ascomycetes

Test material

Constituent 1
Chemical structure
Reference substance name:
Methanol
EC Number:
200-659-6
EC Name:
Methanol
Cas Number:
67-56-1
Molecular formula:
CH4O
IUPAC Name:
methanol

Method

Target gene:
not applicable
Species / strain
Species / strain / cell type:
other: Aspergillus nidulans diploid strain P1
Details on mammalian cell type (if applicable):
no data
Additional strain / cell type characteristics:
not specified
Metabolic activation:
without
Test concentrations with justification for top dose:
5.2, 5.6, 6.0, 7.0 % (v/v)
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: no data

Results and discussion

Test results
Key result
Species / strain:
other: Aspergillus nidulans diploid strain P1
Metabolic activation:
without
Genotoxicity:
positive
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
7.0 % (lowest concentration to arrest conidial germination)
Vehicle controls validity:
not specified
Untreated negative controls validity:
valid
Positive controls validity:
not specified
Additional information on results:
For the phrase selection in field 'Endpoint' the following source information was used as basis:
Type of genotoxicity: genome mutation
Type of study: other: Mitotic recombination in ascomycetes
Guideline:
Species/strain (Method):
- other: Aspergillus nidulans diploid strain P1

Any other information on results incl. tables

There was a concentration-related increase in non-disjunctions (chromosomal malsegregation) with a maximum of about 3 %. No aneuploidies were noted at the lowest test concentration. The result was statistically significant at two concentrations and a dose-response relationship was evident (IPCS/WHO 1997).

No other forms of malsegregation were statistically significant (1/265 cross-over seen at 6.0 %). The survival was reduced in dose-related manner.

Survival and amount of aneuploidy in Aspergillus nidulans after methanol-treatment:

Concentration [%]

Survival [%]

Scored colonies

Aneuploids (yellow segregants)

counts

[%]

5.2

26

268

0

0

5.6

19

407

6

1.47*

6.0

10

265

8

3.02**

7.0

5

176

0

0

Spontaneous control

0

100

2673

7

0.26

* P<0.01; ** P<0.001

Note: Similar results were obtained with ethanol and other primary aliphatic alcohols. The aneuploidy rate of ethanol reached a maximum of about 10 %.

Applicant's summary and conclusion

Conclusions:
Interpretation of results:
positive