Registration Dossier

Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study planned
Study period:
90 day
Justification for type of information:
TESTING PROPOSAL ON VERTEBRATE ANIMALS
Sub-chronic toxicity study (90-day), oral route (Annex IX, Section 8.6.2.; Test method: EU B.26/OECD TG 408) in rats

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)
- Name of the substance for which the testing proposal will be used [if different from tested substance]: 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 sub-chronic toxicity to rats in a 90-day study (via the oral route) with Reaction products of monoethanolamine and boric acid (1:1) / Reaction products of monoethanolamine and boric acid (1:3). Therefore 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.
No 28-day repeated dose toxicity test are available on either ratios as these are waived due to higher-tier studies are proposed.
In both acute dermal toxicity study (Klimisch Category 1) and acute oral toxicity studies (Klimisch Category 1), Reaction products of monoethanolamine and boric acid (1:1) / Reaction products of monoethanolamine and boric acid (1:3) showed low acute dermal toxicity.

- 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 Reaction products of monoethanolamine and boric acid (1:1) / Reaction products of monoethanolamine and boric acid (1:3) on the sub-chronic toxicity to rats in a 90-day 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

A read-across approach is proposed between of Reaction products of monoethanolamine and boric acid (1:1) and Reaction products of monoethanolamine and boric acid (1:3), with the the sub-chronic toxicity to rats in a 90-day study (via the oral route) only to be conducted on the 1:3 ratio.
The justification for the read-across approach results from the structural similarity of the two reaction products, same manufacturing process from the same starting materials (only the ratio is different), existing physico-chemical, toxicological, environmental fate and ecotoxicological data which already showed good correlation with no significant differences between the two ratios, and additional anchoring studies generated to substantiate the category approach.
The conclusions discussed above suggest similar local and systemic toxicity profiles for the two substances. The use of data from MEA Polyborate 1:3 to read-across to MEA Polyborate 1:1 for the repeated dose toxicity (oral) endpoint is considered to provide sufficient confidence.

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 adaptations in column 2 of Annexes VI to X have been considered in the development of the testing proposal for sub-chronic toxicity to rats in a 90-daystudy (via the oral route) to provide data to address the data gap.

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 Reaction products of monoethanolamine and boric acid (1:3) will be tested for sub-chronic oral toxicity in an OECD Guideline for testing of chemicals 408 “Subchronic Oral Toxicity – Rodent: 90-day study” and under GLP.

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
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity in Rodents)

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

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion