Registration Dossier

Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study was conducted according to OECD 471 with one acceptable restriction (TA102 or E.Coli WP2uvrA were not tested. However, this acid chloride is not supposed to have any oxidizing or crosslinking propertiers. Beyond this, a mixture containing high ammounts of stearic acid chloride was negative for E.Coli WP2uvrA).

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report date:
1993

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
TA102 or E.Coli WP2uvrA were not tested
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Chemical structure
Reference substance name:
Stearoyl chloride
EC Number:
204-004-5
EC Name:
Stearoyl chloride
Cas Number:
112-76-5
Molecular formula:
C18H35ClO
IUPAC Name:
octadecanoyl chloride
Details on test material:
- Name of test material (as cited in study report): Stearylsäurechlorid
- Physical state: liquid
- Color: yellowish
- Analytical purity: not reported
- Impurities (identity and concentrations): not reported
- Expiration date of the lot/batch: not reported
- Stability under test conditions: supposed to be stable

Method

Target gene:
His -
Species / strain
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Metabolic activation system:
Liver S9 mix of at least 5 male Sprague-Dawley rats treated with a single ip dose of 500 mg Aroclor 1254/kg bw 5 days prior to sacrifice
Test concentrations with justification for top dose:
0, 20, 100, 500, 2500 and 5000 µg/plate
Vehicle / solvent:
acetone
Controls
Untreated negative controls:
yes
Remarks:
untreated (sterility control)
Negative solvent / vehicle controls:
yes
Remarks:
acetone
Positive controls:
yes
Remarks:
strain specific controls were used
Positive control substance:
other: Positive control were with S9-mix 2-aminoanthracene (TA 1535, TA 1537, TA 98, TA 100); without S9-mix N-methyl-N'-nitro-N-nitrosoguanidine (TA 100, TA1535) 4-nitro-o-phenylendiamine (TA 98), 9-aminoacridine chloride monohydrate (TA 1537) .
Details on test system and experimental conditions:
METHOD OF APPLICATION: standard plate assay and preincubation test
DURATION
- Preincubation period: 20 min
- Test: 48 h

NUMBER OF REPLICATIONS: 3
NUMBER OF CELLS EVALUATED:
DETERMINATION OF CYTOTOXICITY
- Method: mitotic index; cloning efficiency; relative total growth; other:






Evaluation criteria:
Positive results
- doubling ot the spontaneous mutation rate
- dose response relation ship
- reprocibility of thze result
Statistics:
Mean and standard deviation calculated

Results and discussion

Test results
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:
cytotoxicity
Remarks:
A bacteriotoxic effect was observed depending on the strain and test conditions from about 500 µg - 2500 µg/plate onward .
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: precipitation of test substance was seen fom about 500 µg/plate onward

COMPARISON WITH HISTORICAL CONTROL DATA:


Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'. Remarks: S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Any other information on results incl. tables

Valid vehicle controls as well as valid positive and negative controls were demonstrated in experiment 1 & 2. Positive control were with S-9 mix 2-aminoanthracene (TA 1535, TA 1537, TA 98, TA 100); without S-9 mix N-methyl-N'-nitro-N-nitrosoguanidine

(TA 100, TA1535) 4-nitro-o-phenylendiamine (TA 98), 9-aminoacridine chloride monohydrate (TA 1537) .

Controls gave expected results. In the standard plate test as well as in the preincubation assay no increase in the number of revertants was detected in any strain with and without MA.

Applicant's summary and conclusion

Executive summary:

The study is conducted according to the OECD Guideline 471 with acceptable restrictions (not tested in S. typhimurium TA102 or E. coli WP2uvrA). Steaorylchloride was tested in the standard plate test as well as in the preincubation assay with and without metabolic activation (MA) in S. typhimurium TA98, TA100, TA1535, and TA1537 at dose levels of 20 -5000 μg/plate. No increase in the number of revertants was detected in any strain with and without MA. Vehicle, negative and positive controls were valid.

The test substance was not tested in TA102 or E. coli WP2uvrA, however, no oxidizing or cross-linking activity of the test substance is expected. Conclusion: Stearoylchloride has no mutagenic activity in S. typhimurium TA98, TA100, TA1535, and TA1537 with and without metabolic activation at dose levels up to 5 mg/plate.

Conclusion

Stearoyl chloride has no mutagenic activity in S. typhimurium TA98, TA100, TA1535, and TA1537 with and without metabolic activation at dose levels up to 5 mg/plate.