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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in bacteria
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:
before 1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Published study but containing sufficient details to be able to judge it reliable for hazard assessment. Part of a programme of work by the NTP. Data tables available for results. TA102 not included. Full documentation in NTP studies available. Read-across based on supporting substance (analogue approach). The data in this record is for the metabolite 2-butoxyethanol (CAS; 111-76-2, EC no 203-905-0) for which the systemic toxicity will be the same. Full details of the justification for the use of an analogue for this end point are included in the document appended to chapter 13 of this dossier.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Unnamed
Year:
1992
Reference Type:
study report
Title:
Unnamed
Year:
2000
Reference Type:
publication
Title:
Unnamed
Year:
1993

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
no
Remarks:
, no significant deviations noted
Principles of method if other than guideline:
Preincubation as per method of Haworth (Env Mutagen, 5 suppl 1, 3-142, 1983)
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Substance described as purest commercial material available, but no further data.

Method

Species / strainopen allclose all
Species / strain / cell type:
S. typhimurium TA 1535
Details on mammalian cell type (if applicable):
- Type and identity of media:
- Culture prepared at 37C overnight with shaking in Oxoid #2 broth or in defined minimal medium supplemented with biotin and histidine. Phenotype analysed at time of use.
Additional strain / cell type characteristics:
not applicable
Species / strain / cell type:
S. typhimurium TA 97
Details on mammalian cell type (if applicable):
- Type and identity of media:
- Culture prepared at 37C overnight with shaking in Oxoid #2 broth or in defined minimal medium supplemented with biotin and histidine. Phenotype analysed at time of use.
Additional strain / cell type characteristics:
not applicable
Species / strain / cell type:
S. typhimurium TA 98
Details on mammalian cell type (if applicable):
- Type and identity of media:
- Culture prepared at 37C overnight with shaking in Oxoid #2 broth or in defined minimal medium supplemented with biotin and histidine. Phenotype analysed at time of use.
Additional strain / cell type characteristics:
not applicable
Species / strain / cell type:
S. typhimurium TA 100
Details on mammalian cell type (if applicable):
- Type and identity of media:
- Culture prepared at 37C overnight with shaking in Oxoid #2 broth or in defined minimal medium supplemented with biotin and histidine. Phenotype analysed at time of use.
Additional strain / cell type characteristics:
not applicable
Species / strain / cell type:
S. typhimurium TA 1537
Details on mammalian cell type (if applicable):
- Type and identity of media:
- Culture prepared at 37C overnight with shaking in Oxoid #2 broth or in defined minimal medium supplemented with biotin and histidine. Phenotype analysed at time of use.
Additional strain / cell type characteristics:
not applicable
Metabolic activation:
with and without
Metabolic activation system:
Aroclor 1254 induced male SD rat and male Syrian hamster liver S9 fraction, each used at two concentrations (10% and 30%)
Test concentrations with justification for top dose:
100, 333, 1000, 3333, 10000 ug/plate
Vehicle / solvent:
Water
Controlsopen allclose all
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
sodium azide
Remarks:
Migrated to IUCLID6: used for TA1535 and TA100 without metabolic activation
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
9-aminoacridine
Remarks:
Migrated to IUCLID6: used for TA97 without metabolic activation
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 4-nitro-o-phenylenediamine used for TA98 without metabolic activation
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 2-aminoanthracene for all strains with metabolic activation
Details on test system and experimental conditions:
METHOD OF APPLICATION: preincubation

DURATION
- Preincubation period: 20 mins at 37C
- Expression time (cells in growth medium): 2 days at 37C

NUMBER OF REPLICATIONS: 3

DETERMINATION OF CYTOTOXICITY
- Dose range for main test assessed using TA100. Toxic concentrations defined as those producing a decrease in the background number of his+ colonies and/or a clearing in the background lawn. If no toxicity was seen, the maximum dose tested was 10000ug/plate
Evaluation criteria:
Only considered non mutagenic if negative in all strains with and without activation and with both S9 extracts at both concentrations
Statistics:
no data

Results and discussion

Test resultsopen allclose all
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Remarks:
up to maximum dose tested (10000ug/plate)
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 97
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
ADDITIONAL INFORMATION ON CYTOTOXICITY: some evidence of cytotoxicity at top dose in TA100 and TA98.
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative

There was no evidence of mutagenicity in any of the strains tested in the absence of metabolic activation and in the presence of either of the metabolic activation extracts, rat or hamster, at either of the concentrations tested.
Executive summary:

In a reverse mutation assay in bacteria strains TA97, TA98, TA100, TA1535 and TA1537 using the substance 2 -butoxyethanol there was no evidence of mutation with and without metabolic activation systems derived from two species (rat and hamster) used at two different concentrations. These results can be extrapolated to the acetate ester of this substance.