Sodium methanolate

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Information on the genotoxic potential of sodium methanolate is limited to an in vitro mutagenicity test (Ames test, result: negative). Taken into account the available in vitro data on genotoxicity of the hydrolysis products methanol and sodium hydroxide, there were some ambiguous or positive results observed in different in vitro genotoxicity tests with methanol, which were further evaluated in vivo. However, the most of the available in vitro studies with methanol were negative. For sodium hydroxide there is no evidence for a mutagenic potential.

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

only 3 strains testet (TA97, TA98, and TA100)

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Target gene:

his operon

Species / strain / cell type:

S. typhimurium TA 100

Species / strain / cell type:

S. typhimurium TA 98

Species / strain / cell type:

S. typhimurium TA 97

Metabolic activation:

with and without

Metabolic activation system:

S9-mix

Test concentrations with justification for top dose:

8, 40, 200, 1000 and 5000 µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: sterile distilled water

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

2-nitrofluorene

sodium azide

other: 2-aminoanthracene

Evaluation criteria:

a two fold increase in revertants compared to concurrent controls indicates a positive result

Statistics:

RF-test and regression analysis in case of a positive result

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 97

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Species / strain:

E. coli WP2

Metabolic activation:

not applicable

Genotoxicity:

not determined

Cytotoxicity / choice of top concentrations:

not determined

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

not applicable

Genotoxicity:

not determined

Cytotoxicity / choice of top concentrations:

not determined

Conclusions:

negative

Executive summary:

The test substance showed no mutagenicity in the three strains TA97, TA98, and TA100 in the absence and presence of rat liver S9 mix.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

The weight of evidence of all available data for the hydrolysis product methanol suggests that methanol is unlikely to have any relevant mutagenic activity. For sodium hydroxide there is also no evidence for a mutagenic potential. Therefore, it can be concluded that there is no concern with regard to a mutagenic activity for sodium methanolate.

 

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Information on the genotoxic potential of sodium methanolate is limited to an in vitro mutagenicity test (Ames test). The abiotic hydrolysis of sodium methanolate either in aqueous culture media of in vitro test systems or with tissue water results in the formation of methanol (CAS No.67-56-1) and sodium hydroxide (CAS No. 1310-73-2). The latter dissociate into the corresponding cations (Na⁺) and anions (OH^-). Therefore, data of the hydrolysis products were taken into account for the hazard assessment of sodium methanolate (please refer to the endpoint summaries of sodium hydroxide and methanol for details).

 

In vitro

 

A limited GLP-Ames assay similar to OECD guideline 471 with sodium methanolate in only three strains of S. typhimurium TA 97, TA 98 and TA 100 with and without metabolic activation (S9 -mix) at concentrations up to 5000 μg/plate did not show any increase in revertants (Evonik, 1987).

 

Conclusion

No data on mutagenicity of sodium methanolate are available with the exception of one negative Ames assay with a limited number of strains. Due to the rapid hydrolysis of methanolates in in vitro test systems and tissue water in vivo, data for the hydrolysis products are relevant for methanolates as well. For sodium hydroxide there is no evidence for a mutagenic potential. Further testing on the in vitro genotoxicity of sodium hydroxide is considered scientifically unjustified due to the dominating effect of high pH. Testing at non-physiological pH might give false-positive responses, which means that the effect is of a methodical kind and not valid to assess the genotoxicity under realistic conditions. For methanol, the weight of evidence suggests that the substance is unlikely to have any relevant mutagenic activity. For further details please refer to the endpoint summaries of methanol and sodium hydroxide.

Therefore, it can be concluded that there is no concern with regard to a mutagenic activity of sodium methanolate.

Justification for classification or non-classification

The available information on the genotoxic potential of sodium methanolate and its hydrolysis products methanol and sodium hydorxide is conclusive but not sufficient for classification according to CLP (1272/2008/EC) / UN-GHS.

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