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Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
other information
Study period:
Mar 1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: well reported GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report date:
2000

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
no bacteria strain included to detect cross-linking mutagens
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Chemical structure
Reference substance name:
5-Hydroxy-15 beta,16 beta-methylene-3 beta-pivaloyloxy-5 beta-androst-6-en-17-one
EC Number:
617-345-3
Cas Number:
82543-14-4
Molecular formula:
C25 H36 O4
IUPAC Name:
5-Hydroxy-15 beta,16 beta-methylene-3 beta-pivaloyloxy-5 beta-androst-6-en-17-one
Details on test material:
- Name of test material (as cited in study report): ZK 90504
- Batch No.: 21608604

Method

Target gene:
Histidine gene locus
Species / strain
Species / strain / cell type:
other: S. typhimurium TA 1535, TA 100, TA 1537, TA 1538, TA 98
Metabolic activation:
with and without
Metabolic activation system:
liver S9-mix from Aroclor 1254 -treated rats
Test concentrations with justification for top dose:
Enpivalat: six concentrations from 0.1 to 5 mg/plate
Sodium azide: 5 µg/plate (TA 1535 and TA 100, without S9 mix)
2-Nitrofluorene: 10 µg/plate (TA 1538 and TA 98, without S9 mix)
4-Nitro-o-phenylenediamine: 10 µg/plate (TA 1537, without S9 mix)
Benzo[a]pyrene: 2.5 µg/plate (TA 100 and TA 98, with S9 mix)
Cyclophosphamide: 400 µg/plate (TA 1535, with S9 mix)
2-Aminoanthracene: 2 µg/plate (with S9 mix)
Controls
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: Sodium azide (TA 1535 and TA 100, -S9 mix), 2-Nitrofluorene (TA 1538 and TA 98, -S9 mix), 4-NPDA (TA 1537, -S9 mix), Benzo[a]pyrene (TA 100 and TA 98, + S9 mix), Cyclophosphamide (TA 1535, +S9 mix), 2-Aminoanthracene (+S9 mix)

Results and discussion

Test results
Species / strain:
other: Salmonella typhimurium strains TA 1535, TA 100, TA 1537, TA 1538, TA 98
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
Growth inhibition was observed at the highest dose tested. Precipitates in the agar were found starting at 2.5 mg/plate onwards.
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Applicant's summary and conclusion

Executive summary:

Enpivalat was tested in the Salmonella/microsome test for point-mutagenic effects in doses up to 5000 µg/plate on the five histidine-auxotrophic Salmonella typhimurium LT2 strains TA 1535, TA 100, TA 1537, TA 1538 and TA 98.

A cytotoxic effect was seen at the highest dose tested (5 mg/plate). Precipitates in the agar were also detectable starting at 2.5 mg/plate.

There was no evidence for a mutagenic activity of Enpivalat, when tested up to the highest recommended dose level of 5.0 mg/plate in the absence and presence of S9 mix.

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