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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:
experimental study
Adequacy of study:
key study
Study period:
No data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Scientifically undertaken and reported study but not to GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1977
Report date:
1977

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
not specified
GLP compliance:
no
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Chemical structure
Reference substance name:
1,4,5,6,7,7-hexachloro-8,9,10-trinorborn-5-ene-2,3-dicarboxylic anhydride
EC Number:
204-077-3
EC Name:
1,4,5,6,7,7-hexachloro-8,9,10-trinorborn-5-ene-2,3-dicarboxylic anhydride
Cas Number:
115-27-5
Molecular formula:
C9H2Cl6O3
IUPAC Name:
3-({3-carboxy-1,4,5,6,7,7-hexachlorobicyclo[2.2.1]hept-5-ene-2-carbonyloxy}carbonyl)-1,4,5,6,7,7-hexachlorobicyclo[2.2.1]hept-5-ene-2-carboxylic acid
Details on test material:
- Name of test material (as cited in study report): Chlorendic anhydride- Physical state: White powder- Analytical purity: 93.81%- Impurities (identity and concentrations): Chlorendic acid 4.31% Maleic anhydride 0.40%- Purity test date: 16 Aug 77- Lot/batch No.: 3-12-206

Method

Species / strainopen allclose all
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Species / strain / cell type:
S. typhimurium TA 1538
Species / strain / cell type:
Saccharomyces cerevisiae
Additional strain / cell type characteristics:
other: Strain: D4
Metabolic activation:
with and without
Metabolic activation system:
S-9 mix
Test concentrations with justification for top dose:
0.1, 1.0, 10, 100 and 500 µg / plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: DMSO; deionised water- Justification for choice of solvent/vehicle:
Controlsopen allclose all
Untreated negative controls:
yes
Remarks:
Methylnitrosoguanidine
Negative solvent / vehicle controls:
yes
Untreated negative controls:
yes
Remarks:
2-Nitrofluorene
Negative solvent / vehicle controls:
yes
Untreated negative controls:
yes
Remarks:
Quinacrine mustard
Negative solvent / vehicle controls:
yes
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Positive control substance:
other: 2-Anthramine
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Positive control substance:
2-acetylaminofluorene
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Positive control substance:
other: 8-Aminoquinoline
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation); DURATION- Preincubation period: - Exposure duration: - Expression time (cells in growth medium): Overnight- Selection time (if incubation with a selection agent): - Fixation time (start of exposure up to fixation or harvest of cells): 48 hoursSELECTION AGENT (mutation assays): SPINDLE INHIBITOR (cytogenetic assays): STAIN (for cytogenetic assays): NUMBER OF REPLICATIONS: 1NUMBER OF CELLS EVALUATED:DETERMINATION OF CYTOTOXICITY - Method: mitotic index; cloning efficiency; relative total growth; other:OTHER EXAMINATIONS: - Determination of polyploidy: - Determination of endoreplication: - Other: OTHER:
Evaluation criteria:
Evaluation Criteria for Ames AssayMost data sets are evaluated using the following criteria:1. Strains TA-1535, TA-1537, and TA-1538If the solvent control value is within the normal range, a chemical that produces a positive dose response over three concentrations with the lowest increase equal to twice the solvent control value is considered to be mutagenic. 2. Strains TA-98, TA-100, and D4If the solvent control value is within the normal range, a chemical that produces a positive dose response over three concentrations with the highest increase equal to twice the solvent control value for TA-100 and two to three times the solvent control value for strains TA-98 and D4 is considered to be mutagenic. For these strains, the dose response increase should start at approximately the solvent control value.3. PatternBecause TA-1535 and TA-100 were both derived from the same parental strain (G-46) and because TA-1538 and TA-98 were both derived from the same parental strain (D3052), there is a built-in redundancy in the microbial assay. In general the two strains of a set respond to the same mutagen and such a pattern is sought. It is also anticipated that if a given strain, e.g. TA-1537, responds to amutagen in nonactivation tests it will generally do so in activation tests. (The converse of this relationship is not expected.) While similar response patterns are not required for all mutagens, they can be used to enhance the reliability of an evaluation decision.4. ReproducibilityIf a chemical produces a response in a single test that cannot be reproduced in one or more additional runs, the initial positive test data loses significance.

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:
not determined
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 1538
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not determined
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 98
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not determined
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Species / strain:
Saccharomyces cerevisiae
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not determined
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: other: Overlay plates
Remarks:
Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):negative with metabolic activationnegative without metabolic activationChlorendic anhydride did not demonstrate mutagenic activity under the conditions of this study.
Executive summary:

The test substance was examined for mutagenic activity in a series of in vitro microbial assays emplyoying salmonella and saccharomyces indicator organisms. The compound was tested directly and i nthe presence of liver microsomal enzyme preparation from Aroclor-induced rats. The following results were obtained:

Toxicity test results

The compound was tested over a series of concentrations such that there was either a quantitative or qualitative evidence of some chmically-induced physiological effects at the high dose level. The low dose in all cases was below a concentration that demonstrated any toxic effect. The dose range employed for the evaluation of this compound was from 0.1 ug to 500ug per plate.

Nonactivation test results

The results of the tests conducted on the compound in the absence of a metabolic system were all negative

Activation test results

The results of the tests conducted on the compound in the presence of the rat liver activation system were all negative

Conclusions

The test compound, chlorendic anhydride, did not demonstrate mutagenic activity in any of the assays conducted in this evaluation.