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In vitro: 2 -PO was not mutagenic in Salmonella typhimurium strains TA1535, TA1537, TA98 and TA100, and Escherichia coli strain WP2 uvrA (pKM101) with or without S9 mix. In the chromosome aberration test utlizing human lymphocyets, 2 -PO caused statistically significant increases in the proportion of metaphase figures containing chromosomal aberrations at 1012 µg/mL (a non-toxic guideline limit concentration), when compared to the vehicle control, in the presence of S9 mix only.

In the micronucleus test, 2 -PO did not cause any statistically significant increases in the number of binucleate cells containing micronuclei in cultured human lymphocytes at concentrations of up to 1012 μg/mL (10mM) when compared to the vehicle controls, in both the absence and presence of S9 mix.

In vivo: OS1600 was negative in the mouse bone marrow micronucleus test. Due to the rapid hydrolysis of OS1600 to 2 -PO and the similarities in response between other oximes and their associated oxime silanes, it is appropriate to use the OS-1600 in vivo data to evaluate the genetic toxicity of 2 -PO. 

Furthermore, two genotox assessments were performed in which male rats were exposued to 2 -PO via inhalation, 6 hours per day, 5 days per week. The first one, a chromosome aberration test according to OECD 475 showed that, under the conditions of the test, 2 -PO did not induce chromosomal damage in bone marrow cells. In the second test, a Comet assay similar to OECD 489 did not result in the induction of primary DNA dammage in hepatocytes of the test animals.

Based on the measurement of MPKO and its metabolites in the blood of the rats after a single (6 -hour) exposure by inhalation (Report #V20451/01) it is concluded that MPKO has reached the blood, and therefore the systemic exposure has occured at the highest attainable exposure condition. This implies that the in vivo chromosome aberration and comet assay are valid assays. In the presence of systemic exposure MPKO was not genotoxic in in vivo condition.

Based on this battery of in vitro and in vivo test, the weight of evidence indicate that 2 -PO is not mutagenic.

Justification for selection of genetic toxicity endpoint

Data for OS-1600 was used as an analog for 2-PO for the in vivo study. OS-1600 quickly hydrolyzes releasing the oximes and the silicon moieties

which simultaneously cross link to other silicon atoms forming a silicone polymer.  The relevant species in the case of OS-1600 is 2-PO.

Short description of key information:

In vivo and in vitro genetic toxicology studies indicate that 2-PO is not genotoxic.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

2 -PO was not mutagenic in a battery of in vitro and in the vivo genetic test. No classification is necessary.