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 (1:1)

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.

- (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.

- Grouping and read-across
It is proposed that a 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.

We propose a tiered testing strategy: where additional tests are required under Annexes IX and X; it is proposed that these tests be conducted sequentially where relevant (e.g. to address the same endpoint), for the reasons outlined below. As part of this tiered strategy the developmental study (EU B.31/OECD TG414) will be conducted prior the 90-day study (OECD TG 408).
i. Results from one test may render a subsequent test unnecessary, as appropriate classification and labelling information and risk management measures may be able to be derived from these without other tests.
ii. Results from one test may help as range finders for subsequent tests and/or may help in refining the protocol.
iii. On the grounds of animal welfare (as outlined in REACH recitals 13, 33, 37, 40, 49, 50, 64 and especially 47), and Article 13(1) and (2)), in vivo tests on vertebrate animals are to be minimised and avoided where possible. Utilisation of a tiered testing strategy, in which additional tests are potentially avoided dependent on the results of preceding tests, is desirable and consistent with the aims and objectives of REACH.

Data source

Materials and methods

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

Test material

1
Reference substance name:
Reaction products of monoethanolamine and boric acid (1:1)
EC Number:
701-025-6
Cas Number:
94095-04-2
Molecular formula:
C2H7NO.BH3O3
IUPAC Name:
Reaction products of monoethanolamine and boric acid (1:1)
Test material form:
liquid
Details on test material:
Appearance: Clear colourless liquid
Purity/Composition: UVCB
Test item storage: At room temperature protected from light
Stable under storage conditions until: 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