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PENTACELOROPHENOL BACKGROUND INFORMAT ION Pe ntach lorophenol ( commonly c al led penta) is a white cry s tat or powder formulated by chlorinating molten phenol in the presence of a catalyst. The production of this material results in other condensation products, particularly polychlorinatet dioxins and furane. Pentachlorophenol is used primarily in wood preservation. In 1977, 50 million pounds were produced, of which 80 percent was used for wood preservation, ant most of the remainder was used in fungicide products applied to leather, burlap, masonry, cordage, paint, and paper. Although pentachlorophenol can be applied to soil to control termites, as a tenmiticide it has been limited to specific situations, such as direct application to termite-infested wood structures that cannot be easily replaced. Physical and chemical properties of pentachlorophenol are shown in Table 1. SUMMARY OF TOXICITY INFORMATION Several comprehensive reviews on pentachlorophenol are availabl e (NRC, 1977b; IARC, 1979; EPA, 1979e; Rao, 1978~. Information on the toxicity 0 f pentachloropenol is compl icated by the presence of contaminants, such as dibenzo-=dioxins and dibenzofurans, in technical pentachloropt~enol samples. Several studies beve shown that much of the toxicity of pentachlorophenol can be attributed to the presence of these contaminants (Goldatein et al., 1977; Johnson et al., 1973; Kimbrough and Linder, 1975; McConnell et al., 1980; Schwetz _ al., 1973~. Therefore, interpretation of the results of toxicity studies with pentachlorophenol must consider the chemical composition of the pentachloropenol supples tested. EFFECTS IN MU - NS The toxic effects of peneachlorophenol are associated with uncoupling o f oxidat ive pbo ~ pory1 at ion. Cherac teris t ic obe errant ions inc lude lose of appetite, respiratory difficulties, hyperpyrexia, sweating, dyspoea, and coma (Heron, 1958~. Pentachloropenol is readily absorbed through the skin. Twenty infants became ill and two died after coming into contact with nursery linens that bat been washed with a laundry product containing the sodium salt of pentachloropenol (Armatrong et al., 1969~. The clinical features were characteristic of an increased metabolic rate and included tachycardis, tachypnes, fever, sweating, and acidosis. Only a few reports in the literature have deacribet the effects of airborne exposure to pentachlorophenol, and these did not report the extent of exposure. Eighteen workers involved in treatment of wood products with pentachlorophenol were studied by Begley et al. (1977~.

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Renal~clearance tests (creatinine and phosphorus) were conducted on the last day of a work period, the twentieth day of a vacation, and the fifty-firat day after return from vacation. Pentachlorophenol was also measured in the blood and urine. Results of renal clearance tests were reported to be below normal in 16 of the workers before the vacation. Results returned to normal in all but sixworkere by the end of vacation. Clearance had again decreased 51 d after return to work, but not to the extent observed before vacation. B1 Cod and urinary pentachlorophenol concentrations decreased by 56 percent by the end of vacation. Bergner et al. (1965) reported five cases of poisoning in workers with respiratory end dermal exposure to pentachlorophenol. Clinical symptoms included sweating, weight lose, gastrointestinal complaints, and hyperpyrexia; there was one fatality. Urinary pentachlorophenol in the four survivors ranged from 2.4 to 17.5 mg/L. Bander and Bauer (1951) described effects in 10 workers involved in pentachlorophenol production. Exposure to other chlorinated benzol derivatives also occurred. Symptoms included eye irritation, bronchitis, and acne. In some of the workers, acne did not develop until several months after exposure ended. In nine of the workers, acne was still present in various degrees more than a year later. EFFECTS IN ANIMALS Acute Exposure The oral LDso of pentachlorophenol for rats is 146~175 mg/kg, and the dental LD,o is 320~330 mg/kg (Gaines, 1969). Symptom of intoxication include accelerated respiration, vomiting, increased body temperature, tachycardia, neuromuscular weakness, and cardiac failure. Su bchronic Exposure Several studies have reported on oral administration of pentachlorophenol for 90 d. Knudeen et al. (1974) administered pentachlorophenol in the diet to Wistar rats at 0, 25, 50, and 200 ppm (0, 1.25, 2.5, and 10 mg/kg per day, respectively). At 200 ppe, growth rate was reduced in females and liver weight was increased in males. At 50 ant 200 ppe, hemoglobin was increased at 6 wk. but decreased by 11 wK. No adheres effects were on served at 25 ppm. Kimbrough and Linder (1975) gave male rate pure or technical pentachloropbenol at 1,000 ppm. Pathologic changes in the liver were observed and were of ~ greater magnitude with the technical sample. Spragu - Dawley rats given technical pentachlorophecol at 3 mg/kg per day hat increased liver and kidney weights (Johnson ee al., 1973). When the sample was purified to reduce the amount of tioxins, no effects were seen at this dosage. 34

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Chronic Exposure and Care inogenic ity The potential carcinogenicity of pentachlorophenol was studied by Innes et al. (1969) and by Schwetz et al. (19781. Both studies failed to reveal any increased incidence of neoplasia. In the Schwetz et al. ( 1978) study, Sprague-Dawley rats were given a pentachloropbenol sample (having a lower content of nonphenolice than does technical pentachlorophenol) in the diet at 0, 1, 3, 10, and 30 mg/kg of body weight per day; males were exposes for 22 ma, and females for 24 mot No ~ ignif icant increas e in tumors was obeyed a t any dosage. No toxic effects were observed in male rate at 10 mg/kg per day or less or in females at 3 mg/kg per day or less. In the other study (Innes et al., 1969), two strains of mice were given commercial pentachloropbenor~impurities not specified) by stomach tube at 46.4 mg/kg of body weight from 7 to 28 d of age and then at 130 mg/kg in the diet for up to 78 wk. No significant increase in tumors was observed. Teratogenicity and Reproductive Effects Schwetz et al. (1974) analyzed the effects of purified and commercial grades of pentachloropt~enol on rat eetbryonal and fetal development. Sprague-l)awley rats were given pure pentachlorophenol or a commercial grade at 5, 15, 30, and 50 mg/kg of body weight on days 6-15 of gestation. Embryotoxicity and fetotoxicity--as indicated by such effects as resorption, subcutaneous edema, and anomalies of the skull, ribs, and vertebrae~were obeer~red at 15 mg/kg and greater. The no-obeerved-adveree-effect dosage for commercial pentachlorophenol was 5 mg/icg; delayed ossification of the skull was observed with purified pentachlorophenol at this dosage. In a second study, Schwetz et al. (1978) reported that a purified grade of pentachlorophenol given to rats in the diet at 3 mg/kg of body weight for 62 t before mating, during 15 d of mating, and throughout gestation and lactation had no effect on reproduction or neonatal survival, growth, or development. At 30 mg/kg, there was a reduction in body weight among~adult rats and a decrease in neonatal sur~riva1 and growth. Larsen _ al. (1975) reported a reduction in fetal weight when CD rats were given an oral dose of pentachlorophenol at 60 mg/kg of body weight on days B-13 of gestation. Fetal deaths and resorptions were observed in hamsters when doses of 5~20 mg/kg were given on days 5-10 of gestation (Hinkle, 1973~; no effects were reported at 1.25 or 2.5 mg/kg. Mu tagenic ity Vogel and Chandler ( 19 74) reported that pentachlorophenol did not induce sex-linked recessive lethale in Drosophila melanogaster. 35

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Toxicokinet ice Pentachlorophenol is excreted primarily in the urine in the free form (75 percent); other metabolic products include tetrachlorohydroquinone and glucuronide conjugates (Ahlborg et al., 1974; Ahlborg and ~hunberg, 1978~. Metabolism of pentachiorophenol is mediated by microsomal enzymes. Pentachiorophenol is eliminated from the body fairly rapidly. Braun and Sauerhoff (1916) and Braun et al. (1977) reported chat, after a dose of 10 mg/kg body weight, the plasma half-life is 15 ~ in rats and 78 h in monkey e. Tissue concentrations of pentachlorophenol were highest in the 1 iver and kidneys. EX ISTING GUIDELINES AND STANDARDS On the bests of a 90-d feeding study (Johnson et al., 1973) in which a no-obeerved-adverse-effect level of 3 mg/kg per day was reported, the NRC (1977b) calculated a no-adverse-effect-level in drinking water of 0.021 mg/L, for a 70-kg man consuming water at 2 L/d with the assumption that 20 percent of the total intake of pentachlorophenol would be from water. fine EPA (1979e) has suggested art ambient~water quality criterion for pentachloropenol of 0.14 mg/L. The ACGIH (1981) has recommended a TLV-TWA of 0.5 mg/~3 and a ILV-STEL of 1.5 mg/~3. The OSIlA (1981) permissible workplace exposure ~ imit is nenta chloro cheno 1 O.S mg/~3. Both agencies noted that ,~ , is absorbed through the akin and that dental exposure should therefore be avoided. - 36 -