3,5-di(undecan-2-yl)heteropolycycle

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and no systemic effects have been observed in in vivo studies with dermal exposure (e.g. skin irritation, skin sensitisation)

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 434 (Acute Dermal Toxicity - Fixed Dose Procedure)

Deviations:

not specified

Applicant's summary and conclusion

Executive summary:

An update of the tonnage band to 10-100 tonnes is planned for x.y-dialkyldihydro-oxazolo-oxazole (Sa 190). In that respect a step-wise approach shall be applied in order to generate and provide the data required according to the relevant Annex VIII of the REACh regulation. We have identified genotoxicity as a knock-out criterion for further using Sa 190 in our products. Therefore, as a first step we have conducted in vitro genotoxicity tests as required according to Annex VIII, Section 8.4 - namely an in vitro chromosome aberration (OECD TG 473) and an in vitro gene mutation test with mammalian cells (HPRT, OECD TG 476).

While the gene mutation test yielded a negative result, the chromosome aberration test was positive (see study results in section 7.6.1). Taking into account the available negative results of gene mutation tests (1. with bacteria (AMES) and 2. with mammalian cells (HPRT)), from a scientific point of view there is no concern with regard to gene mutation. However, since the in vitro chromosome aberration test was positive, the substances might have a clastogenic potential.

According to the REACH regulation, "appropriate in vivo mutagenicity studies shall be considered in case of a positive result in any of the genotoxicity studies in Annex VII or VIII". A micronucleus assay according to OECD TG 474 is such an appropriate study from our perspective. In section 7.6.2 of this dossier we therefore propose to conduct an in vivo micronucleus assay.

In addition to the clarification required by the the REACh regulation, we will discontinue using x.y-dialkyldihydro-oxazolo-oxazole (Sa 190) in our products if a clastogenic potential would be confirmed, and thus we would also not need to update the tonnage band in this case. Therefore, we decided not to continue the preparations for the planned tonnage band update until it is clarified whether x.y-dialkyldihydro-oxazolo-oxazole (Sa 190) has a clastogenic potential. Toxicological data other than the mentioned in vitro genotoxicity results required for the tonnage band of 10 - 100 tonnes are therefore not yet available but will be generated and provided as soon as possible after a negative outcome of the proposed in vivo micronucleus test.

Please see also testing proposal in Chapter 7.6.2