Introduction
People exposed to pentachlorophenol, a chlorinated aromatic compound, are exposed to a complex mixture that includes by-products formed or present during its production (collectively referred to as PCP). The most predominant by-products are higher-chlorinated dioxins and furans, polychlorinated phenols, and hexachlorobenzene. In the United States, PCP is no longer produced, and its use has been restricted since 1984 to the treatment of utility poles, cross arms, wooden pilings (e.g., wharf pilings), fence posts, and lumber or timbers for construction. Occupational exposure occurs through dermal contact from treating or using treated lumber and inhalation exposure during PCP production and other work activities. PCP has been detected in urine samples taken from the general population, although urinary levels have been decreasing since 1984.
Methods
The National Toxicology Program (NTP) conducted a cancer hazard evaluation of PCP using systematic review methods to identify studies, evaluate study quality, integrate evidence across studies, and integrate evidence across data streams (human, animal, and mechanistic data). Using the Report on Carcinogens (RoC) listing criteria, NTP reached conclusions on the strength of evidence for the carcinogenicity of PCP from studies in experimental animals and humans, and the overall listing recommendation.
Results and discussion
Human cancer studies
Epidemiological studies provide limited evidence of a causal relationship between exposure to PCP and non-Hodgkin lymphoma (NHL) based on consistent findings among workers in different occupations and geographical settings. However, alternative explanations cannot be excluded because the evidence is based on a small number of high-quality studies with relatively moderate risk estimates.
Cancer studies in experimental animals
NTP concluded there was sufficient evidence of carcinogenicity of PCP from studies in experimental animals. In mice, dietary exposure to PCP caused tumors (malignant or combined malignant and benign) of the liver in both sexes and blood vessels in females. In male rats, dietary exposure increased incidences of tumors were observed in the tunica vaginalis of the testes and in the nose.
Mechanistic data
The mechanisms by which PCP may cause cancer are not fully understood. Proposed mechanisms include metabolism to genotoxic and mutagenic metabolites that cause DNA damage and chromosome breakage, immunosuppression, and inhibition of apoptosis.
NTP cancer hazard conclusion
NTP concluded that PCP should be listed as reasonably anticipated to be a human carcinogen in the RoC. The Secretary of Health and Human Services approved the listing of PCP in the 13th RoC. The rationale for the listing was limited evidence from studies in humans, sufficient evidence from studies in experimental animals, and supporting studies demonstrating the biological plausibility of mechanisms of its carcinogenicity in humans. The epidemiological and experimental animal cancer studies cannot separate effects of PCP from its by-products.
National Toxicology Program (NTP). 2014. Report on Carcinogens monograph on pentachlorophenol and by-products of its synthesis. Research Triangle Park, NC: National Toxicology Program. RoC Monograph 03. https://doi.org/10.22427/ROC-MGRAPH-03