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Key value for chemical safety assessment

Additional information

A number of in vitro mutagenicity studies, including bacterial mutation assays in Salmonella typhimurium and Escherichia coli, gene mutation in mammalian cells (L5178Y mouse lymphoma, V79 Chinese hamster cells, C3H/10T1/2 cells), bacterial DNA-damage assay, unscheduled DNA synthesis (hepatocytes), chromosomal aberration and sister chromatid exchange in mammalian cells (Chinese hamster ovary, CHO cells) have been carried out on boric acid and one study on disodium tetraborate decahydrate. No evidence of mutagenic activity was observed.

All the in vitro data indicate no mutagenic activity. In addition the single in vivo study on boric acid also indicated no mutagenic activity.

Read Across

These studies were conducted on an analogue substance. Read-across is justified on the following basis:

In aqueous solutions at physiological and acidic pH, low concentrations of simple inorganic borates such as boric acid, disodium tetraborate decahydrate, disodium tetraborate pentahydrate, boric oxide and disodium octaborate tetrahydrate will predominantly exist as undissociated boric acid. At about pH 10 the metaborate anion (B(OH)4-) becomes the main species in solution (WHO, 1998). This leads to the conclusion that the main species in the plasma of mammals and in the environment is un-dissociated boric acid. Since other borates dissociate to form boric acid in aqueous solutions, they too can be considered to exist as un-dissociated boric acid under the same conditions.

For comparative purposes, exposures to borates are often expressed in terms of boron (B) equivalents based on the fraction of boron in the source substance on a molecular weight basis. Some studies express dose in terms of B, whereas other studies express the dose in units of boric acid. Since the systemic effects and some of the local effects can be traced back to boric acid, results from one substance can be transferred to also evaluate the another substance on the basis of boron equivalents. Therefore data obtained from studies with these borates can be read across in the human health assessment for each individual substance.

Conversion factors are given in the table under CSR section 5.1.3, which corresponds to IUCLID section 7.1 (toxicokinetics, metabolism and distribution endpoint summary).

References:

WHO. Guidelines for drinking-water quality, Addendum to Volume 1, 1998

Short description of key information:

In vitro gene mutation studies in bacteria (Stewart, 1991) in vitro gene mutation studies in mammalian cells (Rudd, 1991) and in vitro cytogenicity studies (NTP, 1987) concluded that boric acid is not genotoxic under the conditions of the studies.  In addition the results of an in vivo bone marrow cytogenetic assay (chromosome aberration assay, O’Loughlin 1991) also showed boric acid to be non genotoxic.

Cytotoxicity observed at 5 mg/mL in the in vitro gene mutation studies in mammalian cells (Rudd, 1991).

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

No classification is required for sodium pentaborate regarding genotoxicity as all results were negative in the tests.