Registration Dossier

Administrative data

Endpoint:
toxicity to reproduction
Remarks:
other: no data
Type of information:
other: no data
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Reliability will be assessed after the study has been conducted.
Data waiving:
other justification
Justification for data waiving:
other:

Data source

Reference
Reference Type:
other: not available
Title:
Unnamed
Year:
2014
Report Date:
2014

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)
Deviations:
not specified
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
other: liquid
Details on test material:
Sa 190

Test animals

Species:
other: no data
Strain:
not specified
Sex:
not specified

Administration / exposure

Route of administration:
other: no data
Type of inhalation exposure (if applicable):
not specified
Vehicle:
not specified
Details on mating procedure:
not available
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
not available
Frequency of treatment:
not available
Details on study schedule:
not available
Doses / concentrations
Remarks:
Doses / Concentrations:

Basis:
no data
No. of animals per sex per dose:
not available
Control animals:
not specified

Results and discussion

Results: P0 (first parental animals)

General toxicity (P0)

Clinical signs:
not specified
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Other effects:
not specified

Reproductive function / performance (P0)

Reproductive function: estrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Reproductive performance:
not specified

Overall reproductive toxicity

Reproductive effects observed:
not specified

Any other information on results incl. tables

not available

Applicant's summary and conclusion

Conclusions:
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. Furthermore, especially in case of the required reproductive toxicity screening test according to section 8.7.1 of Annex VIII it is important to clarify potential genotoxic properties before conducting the test. In case genotoxic properties are confirmed this test might not be necessary. 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.
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. Furthermore, especially in case of the required reproductive toxicity screening test according to section 8.7.1 of Annex VIII it is important to clarify potential genotoxic properties before conducting the test. In case genotoxic properties are confirmed this test might not be necessary. 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.