Pentachlorophenol excretion

Initially formed polar metabolites such as phenols and amines may be conjugated to water-soluble terminal metabolites that are excreted into the medium and function as an effective mechanism of detoxification. For example, pentachlorophenol and pentachlorothiophenol produced from pentachloronitrobenzene conjugated represented the major metabolites. Although the naphthalene dihydrodiol was the major metabolite produced from naphthalene, the further transformation... 

Pentachlorophenol in terrestrial ecosystems clears rapidly (Haque et al. 1988). In one case, a terrestrial ecosystem was given a single surface application of radiolabeled PCP equivalent to 5 kg sodium pentachlorophenate/ha. PCP residues on foliage decreased rapidly, with 50% metabolized within 15 days. After 131 days (autumn), most of the remaining PCP was in the topsoil and plant litter. After 222 days (winter), 39% of the radiocarbon remained. There was little bioconcentration in the resident fauna, due to rapid metabolism and excretion (Haque et al. 1988). 

The toxicity of commercial or technical grades of PCP significantly exceeds that of analytical or purified PCP. Some of this added toxicity is attributed to impurities such as dioxins, dibenzo-furans, chlorophenols, and hexachlorobenzene. Pentachlorophenol is rapidly accumulated and rapidly excreted, and has little tendency to persist in living organisms. It acts by uncoupling oxidative... 

However, PCP is the second heaviest used pesticide in the United States, although it has been mostly used for the purpose of wood preservation(1). Under such circumstances, an international symposium on "Pentachlorophenol" convened by K. Ranga Rao(University of West Florida) was held in Pensacola, Florida, June 27-29, 1977, concerning the chemistry, pharmacology, and environmental toxicology of PCP. At the symposium, I presented a paper(2) on the metabolism of PCP in fishes, mostly reviewing the works on the absorption, excretion and detoxification of PCP in fish and shellfish, which were done in our laboratory. 

Detailed toxicokinetic studies have been performed in both rats (Yuan et al., 1994) and mice (Reigner et al., 1992), comparing intravenous and gavage (and in rat feed) administration of pentachlorophenol. In mice, after either intravenous or oral administration, tlie elimination half-life was about 5-6 h. Only 8% of the dose (15 mg/kg bw) was excreted unchanged in urine, while 20% was excreted as tetrachlorohydroquinone and its conjugates. Sulfate conjugates represented 90% of the total conjugates of pentachlorophenol and tetrachlorohydroquinone. 

G. Renner, Urinary excretion of pentachlorophenol (PCP) and its metabolite tetra-chlorohydroquinone (TCH) in rats. Toxicol. Environ. Chem. 25 29, 1989. 

Disposition in the Body. Readily absorbed after ingestion, inhalation or through intact skin. Pentachlorophenol and its oxidised metabolite, tetrachlorohydroquinone, are excreted in the urine in free and conjugated forms, with about 74% of a dose being excreted unchanged in 7 days. About 4% of a dose is eliminated in the faeces. 

Hexachlorobenzene is slightly absorbed in the gastrointestinal tract but readily distributed in the body, preferentially to fatty tissues. It also readily passes the placenta. Hexachlorobenzene is concentrated in milk. It is metabolized by microsomal enzymes in the liver, kidney, lung, and intestine. Hexachlorobenzene is metabolized slowly by the liver to pentachlorophenol, pentachlorobenzene, tet-rachlorobenzene, and some unidentified compounds. In humans, hexachlorobenzene is mainly excreted in the urine as its metabolites, pentachlorophenol and pentachlorothiophenol. In animals, orally absorbed hexachlorobenzene is excreted, mostly unchanged, in the feces. 

Pentachlorobenzene can be absorbed readily through gastrointestinal and respiratory tracts in humans and experimental animals. Chlorobenzenes accumulate primarily in fatty tissues and have been shown to cross the placenta. Pentachlorobenzene is metabolized via cytochrome P450-dependent processes to its major metabolites pentachlorophenol and 2,3,4,6-tetrachlorophenol. Food restriction was reported to increase its metabolism. Metabolites are excreted in the urine as mercapturic acids, glucuronic acid, or sulfate conjugates. Some proportion of the chemical is eliminated unchanged in the feces. 

The acute oral of pentachlorophenol is 210 mg/kg for rats. In aqueous solutions stronger than 1 % it causes severe skin irritation. It may also be inhaled or absorbed through the skin, but it has no chronic toxic effect because it is rapidly excreted or metabolised. It is toxic to fish, certain species being sensitive to a concentration as low as 0.2 mg/1 (Bevenue and Beckman, 1967). 

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