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International Agency for Research on Cancer (IARC) - Summaries & Evaluations

TRICHLOROACETIC ACID
(Group 3)

For definition of Groups, see Preamble Evaluation.

VOL.: 84 (2004) (p. 403)

CAS No.: 76-03-9

5. Summary of Data Reported and Evaluation

5.1 Exposure data

Trichloroacetic acid is mainly used as a selective herbicide. It also finds use in the metal, plastics and textile industries and as an analytical reagent. It is used in the topical treatment of warts, cervical lesions and other dermatological conditions. Trichloroacetic acid is a major end metabolite of trichloroethylene and tetrachloroethylene. Wider exposure to trichloroacetic acid occurs at microgram-per-litre levels in drinking-water and swimming pools as a result of chlorination or chloramination.

5.2 Human carcinogenicity data

Several studies analysed risk with respect to one or more measures of exposure to complex mixtures of disinfection by-products that are found in most chlorinated and chloraminated drinking-water. No data specifically on trichloroacetic acid were available to the Working Group.

5.3 Animal carcinogenicity data

In four studies, neutralized trichloroacetic acid, when administered in the drinking-water to female and/or male mice, increased the incidences of hepatocellular adenomas and carcinomas. In a study in male rats, trichloroacetic acid did not increase the incidence of liver tumours or tumours at any other site. When administered in the drinking-water, trichloroacetic acid promoted the induction of hepatocellular adenomas and/or carcinomas in carcinogen-initiated male and female mice and of kidney tumours in male mice.

5.4 Other relevant data

The half-life of trichloroacetic acid, given orally or formed as a metabolite of trichloroethylene or trichloroethanol, is longer in humans than in rodents. Trichloroacetic acid may be reduced in vivo to dichloroacetic acid, but the artefactual conversion of trichloroacetic acid to dichloroacetic acid hinders any clear conclusions. A fraction of trichloroacetic acid is metabolized to carbon dioxide.

Trichloroacetic acid induces peroxisome proliferation in the livers of mice at doses within the same range as those that induce hepatic tumours. A brief stimulation of cell division is observed in the liver during the first days of treatment, but depressed cell replication results from chronic treatment. The initial increase in cell proliferation was correlated with decreased methylation of the promoter regions of the c-jun and c-myc proto-oncogenes and increased expression of these genes.

Effects of trichloroacetic acid on reproduction and development in rats have been reported, but were not confirmed in a subsequent study. In-vitro results suggest that trichloroacetic acid can produce teratogenic effects at high doses.

In male mice, trichloroacetic acid modified neither the incidence of mutations in exon 2 of H-ras in carcinomas, nor the mutational spectrum observed in tumours that bore a mutation in exon 2. In female mice, 27% of tumours promoted by trichloroacetic acid exhibited loss of heterozygosity at a minimum of two loci on chromosome 6.

In mouse liver in vivo, measurements of trichloroacetic acid-induced 8-hydroxydeoxyguanosine DNA adducts gave different results depending on the route of administration. Trichloroacetic acid induced abnormal sperm in mice in vivo in one study and chromosomal aberrations in mouse and chicken bone marrow in vivo. The results of in-vivo studies in rodents on the induction of DNA strand breaks and micronuclei were inconsistent. It induced the formation of micronuclei in newt larvae in vivo.

In human cells in vitro, trichloroacetic acid did not induce chromosomal aberrations or DNA strand breaks in single studies. In single studies on cultured rodent cells, trichloroacetic acid was weakly mutagenic; no effect was observed in a DNA strand-break assay or a single-cell gel assay. It also inhibited intercellular communication in cultured rodent cells. Trichloroacetic acid caused neither mutation in bacteria nor SOS repair.

5.5 Evaluation

There is inadequate evidence in humans for the carcinogenicity of trichloroacetic acid.

There is limited evidence in experimental animals for the carcinogenicity of trichloroacetic acid.

Overall evaluation

Trichloroacetic acid is not classifiable as to its carcinogenicity to humans (Group 3).

For definition of the italicized terms, see Preamble Evaluation.

Previous evaluation: Vol. 63 (1995)

Synonyms

       TCA

       TCA (acid)

       Trichloracetic acid

       Trichloroethanoic acid

       Trichloromethane carboxylic acid

Last updated: 29 September 2004



    See Also:
       Toxicological Abbreviations
       Trichloroacetic acid (ICSC)
       Trichloroacetic acid (SIDS)
       Trichloroacetic Acid (IARC Summary & Evaluation, Volume 63, 1995)