Carcinogenicity pentachlorophenol

The role of N-sulfonyloxy arylamines as ultimate carcinogens appears to be limited. For N-hydroxy-2-naphthylamine, conversion by rat hepatic sulfotransferase to a N-sulfonyloxy metabolite results primarily in decomposition to 2-amino-l-naphthol and 1-sulfonyloxy-2-naphthylamine which are also major urinary metabolites and reaction with added nucleophiles is very low, which suggests an overall detoxification process (9,17). However, for 4-aminoazobenzene and N-hydroxy-AAF, which are potent hepatocarcinogens in the newborn mouse, evidence has been presented that strongly implicates their N-sulfonyloxy arylamine esters as ultimate hepatocarcinogens in this species (10,104). This includes the inhibition of arylamine-DNA adduct formation and tumorigenesis by the sulfotransferase inhibitor pentachlorophenol, the reduced tumor incidence in brachymorphic mice that are deficient in PAPS biosynthesis (10,115), and the relatively low O-acetyltransferase activity of mouse liver for N-hydroxy-4-aminoazobenzene and N-OH-AF (7,114,115). 

Pentachlorophenol is not a carcinogen, and the evidence for mutagenicity is mixed. No carcinomas were produced in rodents, regardless of the composition of the PCP solution tested or route of exposure (USEPA 1980 Choudhury et al. 1986). Some studies suggested that PCP may be... 

Among all chlorophenols, 2,4,6-trichlorophenol (TCP) and pentachlorophenol (PCP) are listed as priority pollutants by the US Environmental Protection Agency (EPA) (IRIS electronic database) and the EU [256]. In particular, PCP has been classified as a B2 probable carcinogen for humans from animal toxicity studies and human clinical data. 

Toxicology. Pentachlorophenol has been reported to have adverse effects on the skin, eyes, respiratory system, nervous system, hematopoietic system, kidney, and liver at high doses it is fetotoxic to rats and it is carcinogenic to mice. 

A more recent 2-year study found no evidence of carcinogenic activity for pentachlorophenol in male or female F344/N rats fed diets containing 200, 400, or 600 ppm. There was some evidence of carcinogenic activity in male F344/N rats given feed containing 1,000 ppm for 1 year followed by control feed for 1 year (stop-exposure study), based on increased incidences of mesothelioma and nasal squamous cell carcinoma. 

Two different pentachlorophenol formulations were tested for carcinogenicity by oral administration in two separate experiments 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 (lARC, 1991). 

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

Boberg, E.W., Miller, E.C., Miller, J.A., Poland, A. Liem, A. (1983) Strong evidence from studies with brachymorphic mice and pentachlorophenol that I -sulfooxy safrole is the major ultimate electrophilic and carcinogenic metabolite of 1 -hydroxysafrole in mouse liver. Cancer Res., 43,5163-5173... 

Land treatment has been successfully used to treat soil contaminated with creosote and pentachlorophenol. With weekly tilling, periodic irrigation, and addition of nitrogen and phosphorus when needed, 4347 m3 of soil was successfully treated so that pyrene was reduced from 100 mg/kg to 5 mg/kg, PCP from 150 mg/kg to 10 mg/kg, and carcinogenic PAH from ss 300 mg/kg to 20 mg/kg (Piotrowski et al--, 1994). Treatment times varied from 32 to 163 days, depending on climate conditions and initial concentrations of contaminants. 

Chloracne has been reported in chronic occupational exposure to pentachlorophenol. However, commercial preparations are commonly contaminated with dioxins and furans, and chloracne may be linked to these compounds. In addition, hemolytic and aplastic anemia and weight loss have been reported in humans. Pentachlorophenol is classified as a probable human carcinogen (group 2B). 

BaP is an acknowledged lung carcinogen. Exposure of mice to it results in the formation of DNA adducts in the lung. When BaP was co-adminis-tered with pentachlorophenol (PCP), the PCP potentiated the effect of BaP and a significant increase in the number of DNA adducts was observed. M This effect, however, was observed only in adult mice and not in infant mice. The authors of the study conclude that different mechanisms are involved in the metabolism of BaP for adult versus infant mice. 

Pentachlorophenol is an effective broad-spectrum biocide widely used as a wood preservative. Two-year carcinogenicity studies had been conducted in B6C3F1 mice and similar studies were planned in Fischer 344 rats. To aid in future comparison of the results of the toxicology studies in both species and to provide information for dose-response relationships, toxicokinetic evaluations were conducted. In singlc-and multiple-exposure studies the toxicokinetics of... 

Pesticide chemicals are related to specific toxic effects. With the soil fumigants, reproductive effects and carcinogenicity are the main concern. With the carbamates, such as aldicarb, we are concerned with an acute toxic effect on the peripheral nervous system. With pentachlorophenol high acute toxicity and the potential for carcinogenicity are the main concerns. 

C. In animal studies, pentachlorophenol is mutagenic, teratogenic, and carcinogenic. DNP is teratogenic and may be weakly carcinogenic. 

We prepared the stock solutions of acridine orange, proflavin, ethidium bromide, aniline, benzidine and DAPI in a standard buffer containing 8 mmol/L Tils, 50 mmol/L NaCl and 1 mmol/L EDTA, pH 7.0. The stock solutions of naphthalene, anthracene, phenanthrene, parathion, pentachlorophenol, nitrobenzene, naphthalene, benzo[a]pyrene, dibenz[a,h]anthracene, dibenz[a,j]anthracene, benz[a]anthracene, benzoQ]fluoranthene, benzo[k]fluoranthene, and 1,2,3,4,5,6,7,8-octahydronaphthalene were prepared in ethanol. The concentration of the stock solutions for the carcinogens and hydrocarbons was between 1x10" mol/L and 5x10 mol/L. We carried out serial dilutions with the standard buffer before the experimental measurements. Serial dilutions of the stock solutions were prepared in ethanol using standard buffer containing 5% ethanol. 

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