Trichloroacetic acid

Endpoint summary

Additional information

Trichloroacetic acid has been tested for in vitro genotoxicity in a series of Ames tests, DNA damage and/or repair assays and point mutation assay in Aspergillus nidulans. In all these studies, trichloroacetic acid gave negative results, except in one, in which dimethyl sulfoxide (DMSO) was used as a solubiliser. The evidence supports the hypothesis that a reaction between trichloroacetic acid and DMSO produces a short-lived intermediate product(s) that could be responsible of the time-limited mutagenicity found to be induced by this solution.

Two in vitro cytogenetic assays in human lymphocytes were conducted with trichloroacetic acid. In the first, trichloroacetic acid, as free acid, was added to whole blood cultures in the presence and absence of an auxiliary metabolic activation system (rat liver S9-mix). In the second assay, neutralised trichloroacetic acid was tested also in the presence and absence of S9-mix. Dose-related statistically significant increases in the incidence of chromosomal aberrations, associated with significant reductions in the pH of the cultures treated with trichloroacetic acid were observed. Treatment with neutralised trichloroacetic acid did not result in the induction of chromosomal aberrations. The authors concluded from the results of these two in vitro cytogenetic assays that trichloroacetic acid shows no intrinsic potential to induce cytogenetic damage in the human lymphocyte chromosomal aberration assay when tested up to cytotoxic concentrations.

An in vitro gene mutation assay (method similar to OECD guideline 476) was performed. Trichloroacetic acid was mutagenic only in the presence of S9 activation in L5178Y/TK+/- -3.7.2c mouse lymphoma cells. The authors noted that trichloroacetic acid was the least potent mutagens that they had evaluated.

In-vivo tests were conducted on chromosomal aberrations, DNA strand breaks, oxidative DNA damage and DNA synthesis. An in vivo well conducted bone marrow micronucleus study in mice reported negative results (Mackay et al. 1995). In contrast, statistically significant (but non-dose related) increases in the frequency of cells containing micronuclei were observed in the Bhunya and Behera study (1987). Mackay et al. proposed that the positive results previously observed with trichloroacetic acid may have been due to a non-genotoxic mechanism, possible caused by physicochemically induced stress, resulting from intraperitoneal pH changes.

Short description of key information:
Genetic toxicity in vitro:
Weight of evidence: Results on bacterial reverse mutation assay from several independent sources leading to the conclusion that trichloroacetic acid did not cause point mutations in the microbial systems.

Key study: in vitro gene mutation assay (method similar to OECD guideline 476). Trichloroacetic acid was mutagenic only in the presence of S9 activation in L5178Y/TK+/- -3.7.2c mouse lymphoma cells. The authors noted that trichloroacetic acid was the least potent mutagens that they had evaluated.

Key study: in vitro chromosomal aberration assay in human lymphocytes (method similar to OECD guideline 473). The substance caused an increase in chromosomal aberrations in the presence and absence of metabolic activation but these aberrations were associated with a trichloroacetic acid-induced decrease in pH. When incubations were conducted with neutralised trichloroacetic acid at the same concentrations, significant increases in the incidence of aberrant cells were not observed.

Genetic toxicity in vivo: Key study: Bone marrow micronucleus study in mice. No statistically or biologically significant increases in the incidence of micronucleated polychromatic erythrocytes compared with the solvent control dosed animals were observed in either sex at the 6 h sampling time or in the females at the 24 hr sampling time. A small but statistically significant increase in micronucleated polychromatic erythrocytes was observed in male mice 24 hr after a dose of 675 mg/kg (50% MLD). Since no increases were noted at the 25 or 80% MLD, and the levels recorded are within the range of the concurrent solvent control values, the small increase observed in the males at the 50% MLD is considered not to be biologically significant. No other increases in the micronuclei were observed.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the discussion presented above, it is considered that the available evidence does not suggest that trichloroacetic acid is a mutagen.