5-methoxy-2-methylsulphanilic acid

Endpoint summary

Additional information

No data are available for genetic toxicity of 5-methoxy-2-methylsulphanilic acid. 

We can assume the absence of concern regarding genetic toxicity of 5-methoxy-2-methylsulphanilic acid based on read-across with two compounds of similar structure (more similar substance: 4-aminotoluene-3-sulfonic acid; less similar substance: sulphanilic acid).

For justification of read-across see attachment document in section 13.

In vitro studies

In SIDS Dossier of 4-aminotoluene-3-sulfonic acid approved at SIAM 16 (27 -30 May 2003) many negative in vitro studies regarding genotoxicity of of 4-aminotoluene-3-sulfonic acid are reported:

- in Ames test of 1996 all results were negative up to 5,000 ug/plate in Salmonella typhimurium TA100, TA1535, TA98, TA1537 and Escherichia coli WP2uvrA with and without an exogenous metabolic activation system (see Ministry of Health & Welfare, Japan (1996): Toxicity Testing Reports of Environmental Chemicals, vol.4 p107-110, "Reverse Mutation Test of 2-Amino-5-methylbenzenesulfonic acid on Bacteria").

- negative results were obtained also in a study on Salmonella typhimurium TA100, TA1535, TA98, TA1537, TA1538 (see Report No. CTL/P/1999, Ecological and Toxicological Association of Dyes and Organic Pigments Manufacturers, unpublished report, 1988).

- in chromosomal aberration test with CHL cells 4-aminotoluene-3-sulfonic acid induced weak chromosomal aberration to CHL/IU cell with an exogenous metabolic activation system. However, origin of the aberration was due to the acidity, but not due to physiological DNA damage (see Ministry of Health & Welfare, Japan (1996): Toxicity Testing Reports of Environmental Chemicals, vol.4 p111-114, "In Vitro Chromosomal Aberration Test of 2-Amino-5methylbenzenesulfonic acid on Cultured Chinese Hamster Cells".)

- no DNA damages were observed in unscheduled DNA synthesis assay with human fibroplasts till concentration of 2000 µg/mL of 4-aminotoluene-3-sulfonic acid (see Test No. 850213, AUTORADIOGRAPHIC DNA REPAIR TEST ON HUMAN FIBROBLASTS, CIBA-GEIGY LIMITED, unpublished report, 1985)

- no DNA damages were observed in unscheduled DNA synthesis assay with hepatocytes of male Tif.RAIf rats till concentration of 2000 µg/mL of 4-aminotoluene-3-sulfonic acid (see Test No. 850212, AUTORADIOGRAPHIC DNA REPAIR TEST ON RAT HEPATOCYTES, CIBA-GEIGY LIMITED, unpublished report, 1985)

- negative results for 4-aminotoluene-3-sulfonic acid with Chinese Hamster cells (V79) derived from embryonic lung tissue (see Test No. 850623, V79 CHINESE HAMSTER POINT MUTATION TEST, CIBA-GEIGY LIMITED, unpublished report, 1986)

From information published on ECHA website  different negative in vitro studies regarding genotoxicity of of sulphanilic acid are reported:

- in the Ames test all results were negative up to 1,000 ug/plate in Salmonella typhimurium TA 1535, TA 1537, TA 98 and TA 100 with and without an exogenous metabolic activation system (see Chung et all, PPLIED AND ENVIRONMENTAL MICROBIOLOGY, Oct. 1981, p. 641-648mentioned also in HSDB of sulfanilic acid)

- Sulphanilic acid did not induce structural chromosomal aberrations in human lymphocytes in vitro (reference to experimental study of 2010 on ECHA website)

- negative results for in vitro Mammalian Cell Gene Mutation Test on Chinese hamster lung fibroblasts (V79)for sulphanilic acid (reference to experimental study of 2010 on ECHA website)

The public ECHA database contains data that are proprietary and cannot be used without the formal consent of the owner. In this summary, some of them have been used for precautionary purposes and for the benefit of the human health and the environment. Those data are not necessary for the registration of the target substance which is used exclusively as isolated and transported intermediate, but they can be very helpful for a better definition of the (eco) toxicological property of the substance. No other use and no commercial advantage will derive from the use of those data.

In vivo studies

In SIDS Dossier of 4-aminotoluene-3-sulfonic acid approved at SIAM 16 (27 -30 May 2003) with reference to Report No. CTL/P/2011, Ecological and Toxicological Association of Dyes and Organic Pigments Manufacturers, unpublished report, 1988 in vivo micronucleus assay on C578BL/6JfCD-1/Alpk mice was reported. 4-aminotoluene-3-sulfonic acid was orally administered at 5000 mg/kg and 3125 mg/kg. Though slight cytotoxicity was observed on polychromatic erythrocytes at 5000 mg/kg in males, it did not show a statistically significant increase on the ratio of micronucleated polychromatic erythrocytes at extended count. Therefore, the result of the micronucleus assay was negative.

 

In conclusion, low concern regarding genotoxicity of 5-methoxy-2-methylsulphanilic acid should be assumed based on in vitro and in vivo studies for similar substances.

Justification for selection of genetic toxicity endpoint
Read across with similar substances.

Short description of key information:
5-methoxy-2-methylsulphanilic acid should be not genotoxic based on data available for similar substances.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Low concern regarding genotoxicity of 5-methoxy-2-methylsulphanilic acid should be assumed based on in vitro and in vivo studies for similar substances (4-aminotoluene-3-sulfonic acid and sulphanilic acid).

5-methoxy-2-methylsulphanilic acid should not be classified for genetic toxicity according to annex VI of CLP Regulation (EC n.1272/2008).