2,4-dichlorophenol

Endpoint summary

Additional information

An overall assessment of in vitro tests showed that 2,4-DCP had no effect in Ames tests using various strains of Salmonella typhimurium and Escherichia coli, although ambiguous results were reported using S.typhimurium TA 1535 when exposure occurred in the presence of Aroclor1254-induced male Syrian hamster liver S9 (7.6.1.001) – the result was not repeatable with S9 from rats, and no dose response relationship was discernible. The ambiguous result was obtained in the presence of cytotoxicity. The effects of 2,4-DCP were also studied in vitro in a mammalian cell mutation assay. A positive result was obtained in a mouse lymphoma assay, although again cytotoxicity was present (7.6.1.004). Chromosomal aberrations were observed in the presence of cytotoxicity in two out of the three in vitro chromosome aberration assays examined (7.6.1.007, 008), and sister chromatid exchanges were provoked in an assay with Chinese hamster ovary cells (7.6.1.009). Cell cycle delay/cytotoxicity was observed concurrently with SCEs and this positive result is also likely an artefact of toxicity. An in vitro rat hepatocyte UDS assay did not show mutagenic potential (7.6.1.010). In in vivo tests chromosome aberrations were observed in the bone marrow of rats administered large i.p. injections of 2,4-dichlorophenol, and the results are thought to be an artefact of toxicity although this cannot be verified (7.6.2.002). In an unpublished micronucleus test performed in a way consistent with the OECD Guidelines 474, exposure by gavage (two times at 0 and 24 hr) of Swiss mice to 2,4-DCP at doses up to 800 mg/kgb.w./d did not induce clastogenic effects (7.6.2.001). Most importantly, in a 2-year feeding study in F334/N rats, there was no evidence of carcinogenic activity for males fed diets containing 5,000 or 10,000ppm 2,4-dichlorophenol or females fed diets containing 2,500 or 5,000 ppm of 2,4-dichlorophenol (7.7.001). Similarly, in a 2-year mouse feeding study, there was no evidence of carcinogenic activity for male or for female B6C3F1 mice fed diets containing up to 10,000 ppm 2,4-dichlorophenol (7.7.003). Further support evidence of the absence of tumorigenicity comes from a 2 year study in which rats were administered 2,4-dichlorophenol in the drinking water (7.7.002). Overall it is considered that the clastogenic effects observed in the in vitro studies and an in vivo chromosome aberration study are not relevant to man as it is considered they are an artefact of toxicity. Confirmation that 2,4 -dichlorophenol bears no practical in vivo mutagenic potential comes from the carcinogenicity studies, when after two years administration via the diet or via the water supply no increase in tumours was observed in rats or mice. Therefore classification of 2,4-dichlorophenol as a mutagen cannot be justified. The US National Toxicology Program report (NTP TR 353, see Section 13) concurs, as does the OECD initial assessment report (also attached at section 13).

Short description of key information:
2,4-dichlorophenol was clastogenic in some in vitro assays at cytotoxic doses and in an in vivo bone marrow chromosome aberration study. However other in vivo data including GLP carcinogenicity studies in rats and mice demonstrate no practical in vivo mutagenic potential, in terms of the complete absence of treatment related tumours after two years. The clastogenicity seen in some assays is considered to be secondary to cytotoxicity.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Clastogenicity was observed at high doses in in vitro and in vivo studies, but these results are considered to be an artefact of cytotoxicity. After two years administration of 2,4-dichlorophenol to rats and mice via the diet or via the water supply no increase in tumours was observed. Therefore classification of 2,4 -dichlorophenol as a mutagen cannot be justified. The US National Toxicology Program report (NTP TR 353, see Section 13) concurs, as does the OECD initial assessment report (also attached at section 13).