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

POLYCHLOROPHENOLS AND THEIR SODIUM SALTS
(Group 2B)

For definition of Groups, see Preamble Evaluation.

VOL.: 71 (1999) (p. 769)

CAS No.: 120-83-2
Chem. Abstr. Name: 2,4-Dichlorophenol

CAS No.: 95-95-4
Chem. Abstr. Name: 2,4,5-Trichlorophenol

CAS No.: 88-06-2
Chem. Abstr. Name: 2,4,6-Trichlorophenol

CAS No.: 58-90-2
Chem. Abstr. Name: 2,3,4,6-Tetrachlorophenol

CAS No.: 87-86-5
Chem. Abstr. Name: Pentachlorophenol

5. Summary of Data Reported and Evaluation

5.1 Exposure data

Exposures to chlorophenols and their salts have occurred in their production, in the production of some phenoxy acid herbicides, in the wood industry, the textile industry and tanneries. They have been detected at low levels in ambient air and water.

5.2 Human carcinogenicity data

Mortality and/or cancer incidence has been analysed in several cohort studies of chemical manufacturers, almost all of which have been incorporated within a multicentre international collaborative study, and also in a case–control study nested within this cohort. Two other cohort studies have focused on leather tanneries in Sweden and sawmills in Canada where chlorophenols were used. In addition, case–control studies have examined the association of chlorophenols with soft-tissue sarcoma (one study in New Zealand, four in Sweden and one in the United States), non-Hodgkin lymphoma (one study in New Zealand, one in Sweden and one in the United States), thyroid cancer (one study in Sweden), nasal and nasopharyngeal cancer (one study in Sweden), colon cancer (one study in Sweden) and liver cancer (one study in Sweden).

These investigations have shown significant associations with several types of cancer, but the most consistent findings have been for soft-tissue sarcoma and non-Hodgkin lymphoma. Although the odds ratios in some case–control studies may have been inflated by recall bias, this cannot explain all of the findings. Nor are they likely to have arisen by chance. It is not possible, however, to exclude a confounding effect of polychlorinated dibenzo-para-dioxins which occur as contaminants in chlorophenols.

5.3 Animal carcinogenicity data

2,4-Dichlorophenol was tested in one study in mice and in two studies in rats by oral administration. No increase in the incidence of tumours was found.

2,4,5-Trichlorophenol has not been adequately tested for carcinogenicity.

2,4,6-Trichlorophenol was tested in one study in mice and in one study in rats by oral administration and in one study in mice in a screening test for lung tumours. In mice, it increased the incidences of benign and malignant tumours of the liver and in rats mononuclear cell leukaemia. It did not induce lung adenomas in mice.

No data on the carcinogenicity of tetrachlorophenols in experimental animals were available to the Working Group.

Three different pentachlorophenol formulations were tested for carcinogenicity by oral administration in two experiments in mice and in one study in rats. In mice, a dose-related increase in the incidence of hepatocellular adenomas and carcinomas was observed in males exposed to either formulation and of hepatocellular adenomas in females exposed to one of the formulations. A dose-related increase in the incidence of adrenal phaeochromocytomas was observed in male mice exposed to either formulation, and an increase was also seen in females exposed to one of the formulations at the highest dose. A dose-related increase in the incidence of malignant vascular tumours of the liver and spleen was seen in female mice exposed to either formulation. In rats, no increase in tumours was seen following oral administration of pentachlorophenol for 24 months. However, in rats in the same study receiving a higher concentration for 12 months and held for an additional year, an increased incidence of mesotheliomas of the tunica vaginalis was observed.

5.4 Other relevant data

Chlorophenols are absorbed fairly rapidly, distributed mainly to the kidney and liver and excreted principally via urine; low chlorine-substituted compounds are conjugated with sulfate and glucuronide to a greater extent than the more highly chlorine-substituted compounds. Chlorinated para-hydroquinone formation is a minor metabolic pathway but not for 2,3,5,6-tetrachlorophenol and pentachlorophenol. In rats, the liver is the main target organ. Otherwise, few remarkable effects have been observed.

2,4,6-Trichlorophenol may exhibit weak aneugenic and clastogenic activity. Information on other chlorophenols is inadequate to allow assessment of their genotoxicity.

Pentachlorophenol, after metabolic activation, may exhibit weak clastogenic activity by enhancing oxidative DNA damage.

5.5 Evaluation

There is limited evidence in humans for the carcinogenicity of combined exposures to polychlorophenols or to their sodium salts.

There is evidence suggesting lack of carcinogenicity of 2,4-dichlorophenol in experimental animals.

There is inadequate evidence in experimental animals for the carcinogenicity of 2,4,5-trichlorophenol.

There is limited evidence in experimental animals for the carcinogenicity of 2,4,6-trichlorophenol.

There is sufficient evidence in experimental animals for the carcinogenicity of pentachlorophenol.

Overall evaluation

Combined exposures to polychlorophenols or to their sodium salts are possibly carcinogenic to humans (Group 2B).

For definition of the italicized terms, see Preamble Evaluation.

Previous evaluations: Vol. 20 (1979); Vol. 41 (1986) (Occupational Exposures to Chlorophenols); Suppl. 7 (1987); Vol. 53 (Pentachlorophenol)

Synonyms

2,4-Dichlorophenol

2,4,5-Trichlorophenol

Pentachlorophenol


Last updated: 13 April 1999





















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