Registration Dossier

Administrative data

Endpoint:
extended one-generation reproductive toxicity - basic test design (Cohorts 1A, and 1B without extension)
Remarks:
No further cohorts can be identified at this time as there is no existing data on this substance for the 90-day or development endpoints.
Type of information:
experimental study planned
Justification for type of information:
TESTING PROPOSAL ON VERTEBRATE ANIMALS
Extended one-generation reproductive toxicity study (EOGRTS, Annex X, Section 8.7.3.; Test method: EU B.56, OECD TG 443) 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 reproductive toxicity in rats.
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 in an extended one-generation reproductive toxicity study in rats (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 Expended One-Generation Reproductive Toxicity Study (EOGRTS, OECD 443) to be conducted in MEA Polyborate 1:3. The result will be used to fill the reproductive toxicty information requirements of MEA Polyborate 1:1.

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 8.7.3 of Annex IX of REACH (Extended OneGeneration Reproductive Toxicity Study (B.56 of the Commission Regulation on test methods as specified in Article 13(3) or OECD 443),) states that β€œAn Extended One-Generation Reproductive Toxicity Study with the extension of cohort 1B to include the F2 generation shall be proposed by the registrant.

Testing of the Extended OneGeneration Reproductive Toxicity of rats (via the oral route) on MEA Polyborates 1:3 will address the requirement of Section 8.7.3 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 an Extended one-generation reproductive toxicity study (EOGRTS, Annex X, Section 8.7.3.; Test method: EU B.56, OECD TG 443) in rats or rabbits, oral route will be conducted on MEA Polyborates 1:3 according to OECD Guideline for testing of chemicals 443.
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), whith the EGRTS OECD TG 443 study conducted last.
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
Guideline:
OECD Guideline 443 (Extended One-Generation Reproductive Toxicity Study)
Justification for study design:
No further cohorts can be identified at this time as there is no existing data on this substance for the 90-day or development endpoints.

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)

Results and discussion

Overall reproductive toxicity

Reproductive effects observed:
not specified

Applicant's summary and conclusion