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Key value for chemical safety assessment

Additional information

The reference substance (BAGE) hydrolyses within less than an hour to its hydrolysis products: Boric acid and glycerol. Therefore, conducting studies on the reference substance will give a result representative of the hydrolysis products mentioned above.

Boric acid is considered to be the hydrolysis product of main concern, due to its known reproductive/developmental effects. An assessment of the genotoxicity/mutagenicity of boric acid has therefore been made based on available study data on boric acid.

Boric acid

bacterial reverse mutation assay (e.g. Ames test):

Stewart KR (1991):

The study was performed according to EPA Guideline 84-2 and is comparable to OECD 471.The following bacterial strains were tested: S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 1538, at dose levels of 10; 50; 100; 1000; 2500 μg/plate.

The test substance was not mutagenic in any of the strains tested with or without metabolic activation under the conditions of this study.

unscheduled DNA synthesis in mammalian cells in vitro:

Bakke JP (1991):

An evaluation of the potential of boric acid to induce unscheduled DNA synthesis in the in vitro hepatocyte DNA repair assay using the male F-344 Rat was conducted. Test concentrations of 5, 10, 50, 100, 250, 500, 1000, and 5000 µg/mL were used.

Under the conditions of this study the test substance was not genotoxic.

mammalian cell gene mutation assay:

Rudd (1991):

The study was performed according the test methods equivalent to OECD Guideline 476. Mouse lymphoma L5178Y cells were tested at dose levels of 0, 1.2, 1.7, 2.45, 3.5 and 5.0 mg/mL boric acid (with and without metabolic activation).

The test substance was not mutagenic but cytotoxicity was observed at 5 mg/mL (maximum dose level).

Glycerol

Glycerol is the other hydrolysis product of BAGE. It is not classified for human health according to CLP or DSD and is essentially non-toxic. Further evaluation of the genotoxicity/mutagenicity of glycerol has not been assessed.

Refer to section 13, Toxicological expert report, for further details of the evalaution of the hydrolysis of BAGE and its consequences for toxicity testing.

Supporting data:

DEREK predictions were made to assess the mutagenicity and genotoxicity of the reference substance itself.

The test substance was predicted to be a non- mutagenic as no alerts were triggered for mutagenicity or genotoxicity by the structure of the substance.


Justification for selection of genetic toxicity endpoint
Studies conducted on boric acid, the hydrolysis product of the reference substance, which is of most concern to human health and is most applicable to evaluate.

Short description of key information:
Three in-vitro studies conducted (a gene mutation study in bacteria, a gene mutation study in mammalian cells and a DNA damage and repair assay, unscheduled DNA synthesis in mammalian cells) gave negative results, concluding that boric acid is not genotox/mutagenic.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

No classification is required for boric acid based on the negative results for genotoxicity in three in vitro studies. .