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Key value for chemical safety assessment

Additional information

For the assessment of the mutagenic potential of MAPTAC reliable (RL=1), relevant and adequate studies are available: a reverse gene mutation assay in bacteria (Ames test), a mammalian cell gene mutation assay (HPRT test), and an in vitro mammalian cell micronucleus assay:

Bacterial reverse gene mutation assay

In a reverse gene mutation assay in bacteria according to OECD guideline 471, adopted 21 July 1997, EU Method B.13/14, dated May 19, 2000, TA 98, TA 100, TA 1535, TA 1537, TA 102 strains of S. typhimurium were exposed to MAPTAC (50% in water) at concentrations of 0.0316, 0.100, 0.316, 1.0, 2.5, 5 µL/plate in the presence and absence of mammalian metabolic activation. The test was performed as plate incorporation test and as pre-incubation test.

Up to and including the highest concentration tested of 5 µL MAPTAC/plate, no signs of toxicity were observed. The positive controls induced the appropriate responses in the corresponding strains. There was no evidence of induced mutant colonies over background.

 

Mammalian cell gene mutation assay

In a mammalian cell gene mutation assay according to OECD guideline 476, adopted 21 July 1997 and EU Method B.17, dated May 20, 2008 (HPRT test), V79 cells cultured in vitro were exposed to MAPTAC (50.6% aqueous solution; dose calculation was adjusted to purity) at concentrations of 0 (control), 275, 550, 1100, 2200 and 4400 mg/L in the presence and absence of mammalian metabolic activation (S9 mix).

MAPTAC was tested up to and including the limit concentrations (ca. 10 mM). No signs of cytotoxicity were observed up to and including the highest concentration tested. The positive controls induced the appropriate response.

There was no evidence of induced mutant colonies over background. In this HPRT test, MAPTAC was found to be not mutagenic.

 

In vitro micronucleus assay

In a mammalian cell micronucleus assay according to OECD guideline 487, adopted 22 July 2010, primary human lymphocyte cultures were exposed to MAPTAC (50.6% in water; dose calculation was adjusted to purity) at concentrations of 0 (control), 1436.7, 2514.3 and 4400.0 mg/L with and without metabolic activation (S9 mix). MAPTAC was tested up to and including the limit concentration (ca. 10 mM).

No relevant cytotoxicity, indicated by reduced CBPI and described as cytostasis was observed up to and including the highest applied concentration. A single statistically significant increase was observed in one experiment in the presence of S9 mix after treatment with 2514.3 mg/L. Although this increase of 0.85% micronucleated cells was statistically significant, the response is within the laboratory historical control data range and was not reproducible. Therefore, this finding is regarded as biologically irrelevant. Positive controls induced the appropriate response.

There was no evidence of micronucleated cells induced over background.Therefore, MAPTAC is considered to be non-clastogenic in this micronucleus test, when tested up to and including the limit concentration.

 

Based on the available reliable, relevant and adequate data, there was no evidence of genotoxicity for MAPTAC. There are no data gaps for the endpoint genotoxicity. No human information is available for this endpoint. However, there is no reason to believe that these results would not be applicable to humans.

 


Justification for selection of genetic toxicity endpoint
No single key study has been selected, since all available studies were negative for genotoxicity.

Short description of key information:
MAPTAC is not genotoxic based on the following results:
- not mutagenic in the Salmonella typhimurium reverse mutation assay (OECD guideline 471; GLP)
- not mutagenic in the mammalian cell gene mutation assay (OECD guideline 476; HPRT test, V79 cells; GLP)
- not clastogenic in an in vitro micronucleus test (OECD guideline 487; human lymphocytes; GLP)

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the available data, MAPTAC does not need to be classified for mutagenicity according to the criteria given in regulation (EC) 1272/2008 or the former European directive on classification and labelling 67/548/EEC. Thus, no labelling is required.