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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in mammalian cells
Remarks:
Type of genotoxicity: gene mutation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Published study which contains sufficient detail, including in results, to judge it reliable for hazard assessment purposes. Limited experimental detail provided. No data on vehicle used. Justification for read-across is given in the attached document, Chapter 13: Glycol ether E series Chemical Category

Data source

Reference
Reference Type:
publication
Title:
Mutagenicity testing of diethylene glycol monobutyl ether
Author:
Thompson ED, Coppinger WJ, Valencia R, Iavicoli J
Year:
1984
Bibliographic source:
Environmental Health Perspectives 57, 105-112

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
Deviations:
no
Remarks:
, no significant deviations noted from the information available.
Principles of method if other than guideline:
Test performed according to the method of Clive (Mut Res, 59, 61-108, 1979)
GLP compliance:
not specified
Type of assay:
mammalian cell gene mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): diethylene glycol monobutyl ether, butyl carbitol
- Analytical purity: no data
- Lot/batch No.: S767216
- Other: supplied by Union Carbide Chemical Company (commercial grade material)

Test substance differs from dossier substance in having a butyl terminal alkyl chain rather than a methyl chain.

Method

Target gene:
TK
Species / strain
Species / strain / cell type:
mouse lymphoma L5178Y cells
Details on mammalian cell type (if applicable):
- Type and identity of media:
- Periodically "cleansed" against high spontaneous background: yes, twice weekly
- source: Burroughs-Welcome, Research Triangle Park, NC
Additional strain / cell type characteristics:
not applicable
Metabolic activation:
with and without
Metabolic activation system:
S9
Test concentrations with justification for top dose:
0.42, 0.56-7.5 ul/ml without metabolic activation
0.56-10.0 ul/ml with metabolic activation
Vehicle / solvent:
- Vehicle: yes but no further data. Presumed to be water.
Controlsopen allclose all
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
ethylmethanesulphonate
Remarks:
Migrated to IUCLID6: without metabolic activation, 0.5 and 1.0ul/ml
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
7,12-dimethylbenzanthracene
Remarks:
Migrated to IUCLID6: with metabolic activation, 5 and 7.5uml/ml
Details on test system and experimental conditions:
METHOD OF APPLICATION: plating in selective medium

DURATION
- Expression time (cells in growth medium): 2 days to detect mutation at the TK locus

DETERMINATION OF CYTOTOXICITY
- Method: relative total growth

No further data on method available.
Evaluation criteria:
no data available
Statistics:
no data available

Results and discussion

Test resultsopen allclose all
Species / strain:
mouse lymphoma L5178Y cells
Metabolic activation:
without
Genotoxicity:
ambiguous
Remarks:
see overall remarks
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
>90% between 5.6 - 7.5ul/ml
Vehicle controls validity:
valid
Untreated negative controls validity:
not specified
Positive controls validity:
valid
Species / strain:
mouse lymphoma L5178Y cells
Metabolic activation:
with
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
>90% between 7.5 - 10.0ul/ml
Vehicle controls validity:
valid
Untreated negative controls validity:
not specified
Positive controls validity:
valid
Additional information on results:
no additional information.
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

A potentially ambiguous conclusion arises from a weak positive response in the absence of S9 in the context of a negative response in the presence of S9. Mutation frequencies were 1.75, 3.75 and 4.5 at the top three doses tested (relative to controls) which produced levels of toxicity of 87%, 75% and 40% respectively. Results can be considered ambiguous when the mutatant frequency per viable cell is only 2 -3 times control (especially in the context of the high toxicity). It should be noted that the response is very weak on a molar basis (1umole induces 1.1 mutations per million survivors per hour of exposure compared to 812 for the positive control) and also that there is a lack of response in the presence of S9 and a lack of functional groups associated with genotoxicity in the absence of metabolism. When the relative suspension growth compared to controls was greater than 50%, mutation frequencies were the same as negative control levels.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
ambiguous without metabolic activation
negative with metabolic activation

The substance does not cause genotoxicity in the presence of metabolic activation and the results in the absence of metabolic activation are ambiguous.
Executive summary:

In a mammalian gene mutation study in which the genotoxic potential of 2 -(2 -butoxyethoxy)ethanol was examined in vitro using the the L5178Y TK+/- mouse lymphoma test, ambigous results were obtained in the absence of metabolic activation. Mutation frequencies up to 4.5x those of the solvent control were seen. These result was considered ambigous because of the associated toxicity seen at the higher doses, the lack of biological plausibility, the weakness of the response when expressed on a molar basis relative to positive controls and the fact that the result was clearly negative in the presence of metabolic activation. Because of the structural similarity between this substance and 2 -(2 -methoxyethoxy)ethanol, particularly with respect to function groups and their surrounding atomic environment, this result can be reliably extrapolated to the latter.