1,4,5,6,7,7-hexachloro-8,9,10-trinorborn-5-ene-2,3-dicarboxylic anhydride

Genetic toxicity: in vitro

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

Test material information

Constituent 1

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:

1,4,5,6,7,7-hexachloro-8,9,10-trinorborn-5-ene-2,3-dicarboxylic anhydride

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 / strain

Species / strain 1

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Species / strain 2

Species / strain / cell type:

S. typhimurium TA 1538

Species / strain 3

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:

Controls

Controls 1

Untreated negative controls:

yes

Remarks:

Methylnitrosoguanidine

Negative solvent / vehicle controls:

yes

Controls 2

Untreated negative controls:

yes

Remarks:

2-Nitrofluorene

Negative solvent / vehicle controls:

yes

Controls 3

Untreated negative controls:

yes

Remarks:

Quinacrine mustard

Negative solvent / vehicle controls:

yes

Controls 4

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

other: 2-Anthramine

Controls 5

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

2-acetylaminofluorene

Controls 6

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 results

Test results 1

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

Test results 2

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

Test results 3

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

Test results 4

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.