Allyl 3-cyclohexylpropionate

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study planned

Study period:

The study will be performed depending on ECHA decision.

Justification for type of information:

NON-CONFIDENTIAL NAME OF SUBSTANCE:
- Name of the substance on which testing is proposed to be carried out: allyl 3-cyclohexylpropanoate

CONSIDERATIONS THAT THE GENERAL ADAPTATION POSSIBILITIES OF ANNEX XI OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION
- Available GLP studies
There are no GLP studies available for this substance covering the endpoint of prenatal developmental toxicity
- Available non-GLP studies
There are no non-GLP studies available for this substance covering the endpoint of prenatal developmental toxicity
- Historical human/control data
There are no human/control data covering the endpoint of prenatal developmental toxicity
- (Q)SAR:
(Q)SAR approaches are currently not well fitted-for-purpose for reproductive toxicity and consequently no firm recommendations can be made concerning their routine use in a testing strategy in this area (ECHA Guidance on Information Requirements and Chemical Safety Assessment Chapter R 7a: Endpoint specific guidance, 2017).
- In vitro methods:
There are no in vitro methods available to cover the endpoint of prenatal developmental toxicity.
- Weight of evidence:
There is no data available which is sufficient for a weight of evidence approach.
- Grouping and read-across:
There are no substances with sufficient data which apply for read across addressing prenatal developmental toxicity.

CONSIDERATIONS THAT THE SPECIFIC ADAPTATION POSSIBILITIES OF ANNEXES VI TO X (AND COLUMN 2 THEREOF) OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION:
The substance is fully registered according to REACH Annex IX. Therefore, a study on developmental toxicity in one species is legally required. Furthermore, none of the adaption options from Annex IX, 8.7, column 2 are applicable for the substance, as the substance is not a genotoxic carcinogen, germ cell mutagen or known to cause developmental toxicity and is therefore classified as a reproductive toxicant Category 1 or 2 according to CLP. The test substance must be considered for developmental toxicity testing as due to human exposure according to its intended use, it can be absorbed systemically after oral exposure.


FURTHER INFORMATION ON TESTING PROPOSAL IN ADDITION TO INFORMATION PROVIDED IN THE MATERIALS AND METHODS SECTION:
Details on study design / methodology proposed:
Based on the legal requirements, a Prenatal Developmental Toxicity Study on a second species according to OECD guideline 414 is proposed to assess the effects of the test substance on growth, survival, maintenance of pregnancy of maternal animals and effects on resorptions, fetal deaths fetal growth, morphological variations and malformations of the offsprings of a species other than the rat.
This study is the test system proposed in Annex X, 8.7, column 1 and in the ECHA Guidance on Information Requirements and Chemical Safety Assessment, Chapter R 7a: Endpoint specific guidance, 2017. Under consideration of the substance properties, it is regarded to be the appropriate test system to investigate the potential to induce developmental toxicity, i. e. substances or their metabolites (hydrolysis products) that become readily systemically available upon ingestion. Furthermore, historical control data are available for various tissues. The test substance is proposed to be administered orally by gavage to rabbits as the proposed non-rodent species according to OECD guideline 414. As no repeated dose toxicity data are available in rabbits, doses will be based on a dose range finding test which will be conducted prior to the main experiment. It is noted that the additional time period required for the dose range finding test should also be considered in setting the deadline for submission of data.
Based on the results of the dose range finding test and taken the OECD requirements into consideration, a maximum dose will be chosen as a maximum tolerated dose or, if no effects occur, as the maximum recommended dose of 1000 mg/kg bw/day. Two additional doses (separated by a factor of 2 to 4) are proposed. An appropriate vehicle will be selected in a solubility study together with the testing laboratory, also taking into account the compatibility with the species. Details will be defined in the study protocol.
A sufficient number of female rabbits per dose or control groups to reach a minimum of 20 animals with implantation sites at necropsy will be chosen and is proposed. The test chemical is intended to be administered daily to pregnant animals by gavage, at least from implantation to one day prior to the day of scheduled killing. Shortly before caesarean section, the females will be killed, the uterine contents are examined, and the fetuses are evaluated for fetal deaths, sex, body weight, AGD, soft tissue and skeletal changes. Dams will be observed during the treatment period, weighted, and examined post-mortem. These examinations will include macroscopical structural abnormalities, weight of thyroid glands and uteri, histopathological assessment of thyroid gland and uteri, number of corpora lutea and degree of resorption.

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Test material

Test material information

Constituent 1

Reference substance name:

Allyl 3-cyclohexylpropionate

EC Number:

220-292-5

EC Name:

Allyl 3-cyclohexylpropionate

Cas Number:

2705-87-5

Molecular formula:

C12H20O2

IUPAC Name:

prop-2-en-1-yl 3-cyclohexylpropanoate

Test animals

Species:

rat

Administration / exposure

Route of administration:

oral: gavage