Octahydro-4,7-methano-1H-indene-5-methanol

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

The substance did not induce genetic toxicity in vitro, proved by the results of an Ames Assay.

Link to relevant study records

Reference

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:

Initiation: August 2, 1983 - Termination: September 30, 1983

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

GLP compliance:

yes

Type of assay:

bacterial gene mutation assay

Specific details on test material used for the study:

No information about purity. However, as it is stated in the section 13, the substance and its composition have remained essentially the same over the last decades.

Species / strain / cell type:

other: Salmonella typhimurium TA100, TA1535, TA1537, TA1538, TA98; Escherichia coli WP2uvrA

Metabolic activation:

with and without

Metabolic activation system:

Aroclor 1254 induced male rat liver S9 mix

Test concentrations with justification for top dose:

The test compound proved to be toxic to most of the bacterial strains at 500 µg/plate. 2500 µg/plate was chosen as top dose level for the mutagenicity study.

Experiment 1 (Toxicity experiment and dose range finding): 4, 20, 100, 500, 2500 and 10000 µg/plate
Experiment 2-7 (TA100, TA1535, TA1537, TA1538, TA98 and WP2uvrA): 4, 20, 100, 500, 2500 µg/plate
Experiment 5a (Repitiion of experiment 5 for TA1538 without metabolic activation): 0.16, 0.8, 4, 20, 100, 500, 2500 µg/plate

Vehicle / solvent:

The test substance was dissolved in DMSO at appropriate concentrations.

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

Positive controls:

yes

Positive control substance:

9-aminoacridine

2-nitrofluorene

sodium azide

benzo(a)pyrene

other: N-Methyl-N'-nitro-N-nitrosoguanide, 2-Aminoanthracene

Details on test system and experimental conditions:

Plate incorporation method: Bacterial strain, test compound and S9 mix (if required) added to top agar, mixed and poured into petridish with minimal agar. After incubation for 48 to 72 hours at 37°C in the dark, colonies are counted.

Number of replications: 3 plates per concentration tested

Toxicity experiments: Preliminary toxicity tests were performed with all tester strains using a small number of plates to calculate an appropriate dose range. A reduced rate of spontaneously occuring colonies as well as visible thinning of the bacterial lawn were used as indicator for toxicity. Thinning of the bacterial lawn was controlled microscopically.

Evaluation criteria:

A substance is considered to have mutagenic potential, if a reproducible increase of revertant colonies per plate exceeding an increase factor of 2 in at least one strain can be observed. A concentration-related increase over the range tested is also taken as a sign of mutagenic activity.

Statistics:

The mean values and standard deviations of each threefold determination were calculated as well as the increase factor f(l) of revertant induction (mean revertants divided by mean spontaneous revertants) of the test item solutions and the positive controls.

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

> = 500 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

> 500 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

> 500 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

> 500 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

> 500 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Key result

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

> 500 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

The test substance did not cause a significant increase in the number of revertant colonies with any of the tester strains, neither in the absence nor presence of metabolic activation.

No dose dependent effect was obtained. A small increase in the number of revertants has been obtained with TA1538 without metabolic activation (twice the controle value).

This effect however was not dose dependent and was not seen in a second independent experiment.

Therefore the results in TA1538 did not give any indication of mutagenicity.

Conclusions:

It is concluded that the test substance is not mutagenic in these bacterial test systems neither in the absence nor in the presence of an exogenous metabolizing system.

Executive summary:

TCD Alcohol M was tested for mutagenicity with the strains TA100, TA1535, TA1537, TA1538, TA98 of Salmonella typhimurium and Escherichia coli WP2uvrA.

The mutagenicity studies were conducted in the absence and in the presence of a metabolizing system derived from rat liver homogenate. A dose range of 5 different doses from 4 µg/plate to 2500 µg/plate was used.

Control plates without mutagen showed that the number of spontaneous revertant colonies was similar to that described in the literature. All the positive control compounds gave the expected increase in the number of revertant colonies.

In the absence of the metabolic activation system the test compound did not show a dose dependent increase in the number of revertants in any of the bacterial strains. Also in the presence of metabolic activation system, treatment of the cells with TCD Alcohol M did not result in relevant increases in the number of revertant colonies.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no study available

Mode of Action Analysis / Human Relevance Framework

In the absence of information on species specific effects these information are regarded as relevant for humans.

Additional information

From the results of the Ames test, it can be concluded that TCD Alcohol M is not mutagenic in this bacterial test systems neither in the absence nor in the presence of an exogenous metabolizing system, since it did not cause a significant increase in the number of revertant colonies with any of the tester strains and no dose dependent effect was observed.

Thus, the available results do not give any indication of mutagenicity.

Justification for classification or non-classification

Based on the available in vitro study (Ames test), the test substance has not to be classified according to Regulation (EC) No. 1272/2008.