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Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Chlorine dioxide and chlorite are characterized together for the genetic toxicity because studies conducted with chlorite, the predominant degradation product of chlorine dioxide, are likely relevant to characterizing the toxicity of chlorine dioxide. In addition, studies conducted with chlorine dioxide may be relevant to characterizing the toxicity of chlorite. Chlorine dioxide is fairly unstable and rapidly dissociates, predominantly into chlorite and chloride, and to a lesser extent, chlorate. There is a ready interconversion among these species in water.

Genetic toxicity in vitro:

Bacterial reverse mutation assay: Ames tests: Test method similar to OECD guideline 471:

Weight of evidence: Experimental results: Sodium chlorite was negative when tested with the Salmonella typhimurium strains TA97 and TA102, with and without metabolic activation. Sodium chlorite was negative when tested with the Salmonella typhimurium strains TA 92, TA 1535, TA 1537, TA 94 and TA 98, with and without metabolic activation. Sodium chlorite was positive in S. typhimurium strain TA 100 with metabolic activation.

 

Chromosomal aberrations: Test method similar to OECD guideline 473:

Supporting study: Experimental results: Sodium chlorite was positive in the chromosome test without metabolic activation. However, no data on positive controls are provided. In vivo studies on chromosomal aberrations are available.

 

Gene mutation in mammalian cells: Test method similar to OECD guideline 476:

Key study: Experimental results with the substance chlorine dioxide. The test substance chlorine dioxide is considered active in the Mouse Lymphoma Forward Mutation Assay in the presence and absence of metabolic activation.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

Chlorine dioxide and chlorite are characterized together for the genetic toxicity because studies conducted with chlorite, the predominant degradation product of chlorine dioxide, are likely relevant to characterizing the toxicity of chlorine dioxide. In addition, studies conducted with chlorine dioxide may be relevant to characterizing the toxicity of chlorite. Chlorine dioxide is fairly unstable and rapidly dissociates, predominantly into chlorite and chloride, and to a lesser extent, chlorate. There is a ready interconversion among these species in water.

Genetic toxicity in vivo:

 

Weight of evidence: Experimental results. Data provided are based on bone marrow chromosome aberration tests and micronucleus tests. 

 

Micronucleus assay: publications from two different authors. Test methods similar to OECD guideline 474:

Hayashi et al. (1988): In the single ip treatment, positive results were obtained for sodium chlorite. Sodium chlorite failed to show a statistically significant result after administration by oral gavage. After four ip injections at a dose level of 15 mg/kg bw, negative results were obtained for sodium chlorite.

 

Meier et al. (1985): After oral administration, none of the dose levels tested gave significant increases for either pooled or individual sex data.

 

Chromosomal aberrations: data from a publication. Test method similar to OECD guideline 475:

 

Meier et al. (1988): after oral single administration and multiple oral administration there were no significant differences from control for any of the treatment groups in either structural or numerical chromosomal aberrations.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

Justification for selection of genetic toxicity endpoint
No study was selected, since the results obtained in the in vitro studies (Ames test, Chromosome aberrations test and Mammalian cell gene mutation assay) and the in vivo studies were negative.

Short description of key information:
Genetic toxicity in vitro:
Bacterial reverse mutation assay: Ames tests: Test method similar to OECD guideline 471:
Weight of evidence: Experimental results: Sodium chlorite was only positive in S. typhimurium strain TA 100 with metabolic activation.

Chromosomal aberrations: Test method similar to OECD guideline 473:
Supporting study: Experimental results: Sodium chlorite was positive in the chromosome test without metabolic activation. However, no data on positive controls are provided.

Gene mutation in mammalian cells: Test method similar to OECD guideline 476:
Key study: Experimental results with the substance chlorine dioxide. The test substance chlorine dioxide is considered active in the presence and absence of metabolic activation.

Genetic toxicity in vivo:
Weight of evidence: Experimental results. Data provided are based on bone marrow chromosome aberration tests and micronucleus tests.
Micronucleus assay: publications from two different authors. Test methods similar to OECD guideline 474:
Hayashi et al. (1988): In the single ip treatment, positive results were obtained for sodium chlorite. Sodium chlorite failed to show a statistically significant result after administration by oral gavage. After four ip injections at a dose level of 15 mg/kg bw, negative results were obtained for sodium chlorite.
Meier et al. (1985): After oral administration, none of the dose levels tested gave significant increases for either pooled or individual sex data.

Chromosomal aberrations: data from a publication. Test method similar to OECD guideline 475:
Meier et al. (1988): after oral single administration and multiple oral administration there were no significant differences from control for any of the treatment groups in either structural or numerical chromosomal aberrations.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

A positive result was observed in an in vivo micronucleus assay in somatic cells exposed by the intraperitoneal route. In this case, there are additional data from in vivo tests with oral administration of the test substance showing negative results and the weight of evidence approach has been applied. Furthermore, data from an in vivo study on chromosomal aberrations in somatic cells by the oral route also showed negative results. It seems that genotoxicity can only be shown at internal body substance concentrations which cannot be achieved using application routes other than intraperitoneal. Furthermore, the intraperitoneal route of exposure is not relevant for human exposure.

Hazard classification for germ cell mutagenicity primarily aims to identify substances causing heritable mutations or being suspected of causing heritable mutations. Therefore, this hazard class is primarily concerned with substances that may cause mutations in the germ cells of humans that can be transmitted to the progeny. Based on the available information from different publications from independent sources, on toxicity to reproduction studies and developmental toxicity studies, it can be concluded that the substance showed no evidence of reproductive toxicity.

It is recognised that genetic events are central in the overall process of cancer development. Therefore evidence of mutagenic activity in vivo may indicate that a substance has a potential for carcinogenic effects. Based on the available information from different publications from independent sources, on oral studies with rats and mice by administration in drinking water and dermal studies with female mice it can be concluded that the substance showed no evidence of carcinogenic activity.

Therefore, based on all these arguments, it is concluded that the substance is not classified for germ cell mutagenicity.