Registration Dossier

Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study planned
Study period:
The registrant has a signed a letter of intent with Harlan Laboratories for conduct of this test in 2011. The study will be performed following acceptance of this vertebrate testing proposal by ECHA.

Data source

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Testing of the substance oct-1-ene (CAS RN 111-66-0) is proposed.

Administration / exposure

Details on study design:
For the information requirements of Annexes IX and X, the following data gap was identified after full use of read across and all supporting information. This gap is as follows:

1. Pre-natal Developmental Toxicity
• REACH Endpoint 8.7.2, Annex IX
• OECD 414

Proposal
Linear alpha olefins; isomerised olefins; alpha, internal, linear and branched - single carbon number; and isomerised olefins; alpha, internal, linear and branched – multiple carbon numbers differ from one another only in the carbon number, position of the double bond and or changes in the carbon skeleton structure from linear to branched. The available toxicity data demonstrate that these alterations in structure do not have a discernable impact on toxicity. Furthermore, screening level reproductive/developmental toxicity data on a C6 linear alpha olefin, C14 linear alpha olefins, C18 single carbon number isomerised olefin, and alkenes, C6 multiple carbon number isomerised olefin all demonstrate a low potential for adverse reproductive and or developmental effects.

Given that there does not appear to be any substantial difference in toxicity between these different structures, and given the apparent absence of potential adverse reproductive/developmental effects in screening level studies, it is proposed that the data gaps for reproductive and developmental toxicity be filled by testing one higher olefin substance with read across to all other related structures.

The study protocols will meet the technical requirements of OECD 414 (developmental toxicity), and the tests themselves will be GLP-compliant.

In addition to generating the required data, this approach will also minimise unnecessary vertebrate testing.

Substance selection
The available data indicate that while effects seen in repeated-dose studies with C6 and C14 linear alpha olefins, and alkenes, C6 through alkenes, C20-24 multiple carbon number isomerised olefins indicate some potential for systemic exposure, structures having more than 29 carbon atoms were unlikely to be absorbed to any appreciable extent. Selection of a representative structure from the lower end of the carbon number range of interest will therefore maximise the chances for gastrointestinal uptake and systemic exposure.

Because screening-level reproduction/developmental data are already available from OECD 421/422 studies on C6 linear alpha olefin, C14 linear alpha olefin, C18 single carbon number isomerised oelfin, and alkenes, C6 multiple carbon number isomerised olefin, testing of an additional low carbon number (and hence bioavailable) alpha or internal olefin is proposed.

Testing of the substance oct-1-ene (CAS RN 111-66-0) is proposed.

Results and discussion

Results (fetuses)

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion