Registration Dossier

Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study planned
Justification for type of information:
TESTING PROPOSAL ON VERTEBRATE ANIMALS
Pre-natal developmental toxicity study (Annex IX, Section 8.7.2.; Test method: EU B.31/OECD TG414) in rats or rabbits, oral route

NON-CONFIDENTIAL NAME OF SUBSTANCE:
- Name of the substance on which testing is proposed to be carried out: Reaction products of monoethanolamine and boric acid (1:3)

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 and non-GLP studies
There is no existing reliable (GLP or non-GLP) data on the pre-natal development in rats, nor a 28-day repeated dose toxicity test combined with a reproduction/developmental toxicity screening test.
This is a standard information requirement for which data must be provided. The information on this endpoint is not available for the registered substance, but needs to be present in the registration dossier to meet the information requirements.

- Historical human data:
A literature search and SIEF survey has not identified historical data on human exposure to Reaction products of monoethanolamine and boric acid 1:1/ 1:3 and its toxicological effects. Adaptation based on historical human data, therefore, is not possible.

- (Q)SAR
Due to the presence of inorganics and the complex chemistry, the substance falls outside of the applicability domain of the globally recognized (Q)SAR models. Therefore, no (Q)SAR modelling has been carried out on Reaction products of monoethanolamine and boric acid (1:1) / Reaction products of monoethanolamine and boric acid (1:3)

- In vitro methods
The application of in vitro methods is not relevant to the assessment of the effects of MEA Polyborates 1:1/1:3 on the pre-natal development of rats study (via the oral route) given the biological complexity of the endpoint.

- Weight of evidence: Upon reviewing all available information, including GLP and non-GLP studies, in vitro and QSAR methods, and based on our category approach, a tiered testing approach is proposed. A weight of evidence based adaptation, however, is not considered to be applicable.

- Substance-tailored exposure driven testing: Considering the intended uses of the substance, exposure-driven adaptation is not applicable.

- Grouping and read-across
It is proposed that the developmental toxicity studies (OECD 414) in rat, to be conducted on both MEA Polyborates 1:1 and 1:3, to identify any potential differences in effects and also to inform dose selection of the Expended One-Generation Reproductive Toxicity Study (EOGRTS, OECD 443) to be conducted in MEA Polyborate 1:3. Any potential differences would inform the selection, which ratio to be tested in the 90-day study (OECD 408).


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:
Section 8.7.2 of Annex IX of REACH (Pre-natal developmental toxicity study, one species, most appropriate route of administration, having regard to the likely route of human exposure (B.31 of the Commission Regulation on test methods as specified in Article 13(3) or OECD 414) states that “The study shall be initially performed on one species. A decision on the need to perform a study at this tonnage level or the next on a second species should be based on the outcome of the first test and all other relevant available data”.
Testing of the pre-natal development of rats (via the oral route) on both MEA Polyborates 1:1 and 1:3 will address the requirement of Section 8.7.2 of Annex IX of REACH.

FURTHER INFORMATION ON TESTING PROPOSAL IN ADDITION TO INFORMATION PROVIDED IN THE MATERIALS AND METHODS SECTION:
- Details on study design / methodology proposed
It is proposed that a developmental toxicity study will be conducted on both MEA Polyborates 1:1 and 1:3 according to OECD Guideline for testing of chemicals 414 Pre-natal developmental Toxicity Study. According to the test method EU B.31/OECD TG414, rat is the preferred rodent species and the test substance is usually administered orally.
Further reproductive and developmental studies may potentially be proposed based on the result of developmental studies (OECD TG414) and the EOGRTS study proposed on MEA Polyborates 1:3.

Data source

Materials and methods

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

Test material

Reference
Name:
Unnamed
Test material form:
liquid
Remarks:
clear colourless
Details on test material:
UVCB
At room temperature protected from light
31 March 2018 (expiry date)

Test animals

Species:
rat

Results and discussion

Results (fetuses)

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion