Dioctadecyl 3,3'-thiodipropionate

Toxicity to reproduction

Administrative data

Endpoint:

extended one-generation reproductive toxicity - basic test design (Cohorts 1A, and 1B without extension)

Type of information:

experimental study planned

Justification for type of information:

TESTING PROPOSAL ON VERTEBRATE ANIMALS

NON-CONFIDENTIAL NAME OF SUBSTANCE:
- Name of the substance on which testing is proposed to be carried out: dioctadecyl 3,3'-thiodipropionate

CONSIDERATIONS THAT THE GENERAL ADAPTATION POSSIBILITIES OF ANNEX XI OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION [please address all points below]:
- Available GLP studies: OECD 408 study in rats (ongoing), OECD 414 study in rats (ongoing), OECD 414 study in rabbits (ongoing)
- Available non-GLP studies: not available
- Historical human/control data: not available
- (Q)SAR: not adequate for the endpoint to be addressed
- In vitro methods: not adequate for the endpoint to be addressed
- Weight of evidence: not available
- Grouping and read-across: no relevant data for this endpoint was identified in any of the possible read-across substances (based on structural similarity)
- Based on the properties and uses of the substance, exposure-based waiving is not adequate.


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:
- substance is based on the available data not cancerogenic or mutagenic
- no data on absorption are available, however a structurally similar substance with shorter fatty acid chains was shown to be well absorbed, therefore a degree of systemic bioavailability is expected also for the registered substance.

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 data available at this time, no specific concern for toxicity to reproduction or organ toxicity is foreseen, therefore the basic design with oral route of administration is proposed by the registrant. However, a 90-day study is still ongoing and adaptations to the study design may be required once these data are available.

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 443 (Extended One-Generation Reproductive Toxicity Study)

Version / remarks:

current at the time of study conduct

GLP compliance:

yes

Justification for study design:

SPECIFICATION OF STUDY DESIGN FOR EXTENDED ONE-GENERATION REPRODUCTION TOXICITY STUDY WITH JUSTIFICATIONS [please address all points below]:

- Premating exposure duration for parental (P0) animals: 2 weeks is considered sufficient based on the ADME data available for a structurally similar substance. Based on OECD Guideline 443, "a 2-week pre-mating treatment for both sexes is considered adequate in most cases. For females, this covers 3-4 complete oestrous cycles and should be sufficient to detect any adverse effects on cyclicity. For males, this is equivalent to the time required for epididymal transit of maturing spermatozoa and should allow the detection of post-testicular effects on sperm (during the final stages of spermiation and epididymal sperm maturation) at mating. At the time of termination, when testicular and epididymal histopathology and analysis of sperm parameters are scheduled, the P and F1 males, will have been exposed for at least one entire spermatogenic process." [OECD Guideline 443].
- Basis for dose level selection: Dose selection will be based on the available data and potentially additional dose-range finding experiments
- Inclusion/exclusion of extension of Cohort 1B: While consumer uses for the substance exist, a high exposure is not expected based on the concentrations of substance in consumer articles and since the substance is incorporated into a matrix and very low dermal absorption is expected based on the physical-chemical properties. Further, the substance was not genotoxic, ADME data of a related substance suggest good systemic bioavailability but also fast excretion with no potential for bioaccumulation in man. Therefore, it is expected that the internal dose is reached fast. Further, no endocrine modes of action have been identified for the registered substance or its structurally relative either in vitro or in vivo. Overall, the criteria for extension of Cohort 1B are not fulfilled, therefore these additional examinations are not warranted.
- Termination time for F2: not applicable.
- Inclusion/exclusion of developmental neurotoxicity Cohorts 2A and 2B: based on the available data, no neurotoxicity or concern for neurotoxicity was observed. Similarly, no concern for neurotoxicity was observed in any data available for a related substance. Therefore, additional investigations with the Cohorts 2A and 2B are not warranted.
- Inclusion/exclusion of developmental immunotoxicity Cohort 3: based on the available data, no immunotoxicity or concern for immunotoxicity was observed. Similarly, no concern for immunotoxicity was observed in any data available for a related substance. Therefore, additional investigations with the Cohort 3 are not warranted.
- Route of administration: oral
- Other considerations, e.g. on choice of species, strain, vehicle and number of animals [if applicable]: species will be rat according to the guideline recommendations and available historical control data of the laboratory. Vehicle will be equivalent to the ongoing 90-day study or feed, depending on study design and technical feasibility. Animal numbers will be chosen according to the provisions of the OECD testing guideline.

Test material

Test material information

Constituent 1

Reference substance name:

Dioctadecyl 3,3'-thiodipropionate

EC Number:

211-750-5

EC Name:

Dioctadecyl 3,3'-thiodipropionate

Cas Number:

693-36-7

Molecular formula:

C42H82O4S

IUPAC Name:

dioctadecyl 3,3'-thiodipropionate

Test material form:

solid: flakes

Test animals

Species:

rat

Sex:

male/female

Administration / exposure

Route of administration:

oral: unspecified