NOTE: Although the toxicity values presented in these toxicity profiles were correct at the time they were produced, these values are subject to change. Users should always refer to the Toxicity Value Database for the current toxicity values.
Prepared by: Robert A. Young, Ph.D., D.A.B.T., Chemical Hazard Evaluation and Communication Program, Biomedical and Environmental Information Analysis Section, Health and Safety Research Division, *, Oak Ridge, Tennessee.
Prepared for: Oak Ridge Reservation Environmental Restoration Program.
*Managed by Martin Marietta Energy Systems, Inc., for the U.S. Department of Energy under Contract No. DE-AC05-84OR21400.
Pentachlorophenol, a man-made organic biocide, is often contaminated with other toxic organic chemicals such as chlorinated phenols, dioxins, and dibenzofurans (Williams, 1982; U.S. Air Force, 1989; ATSDR, 1992).
Pentachlorophenol is readily absorbed following oral or inhalation exposure and is widely and rapidly distributed throughout the body (Wagner et al., 1991; ATSDR, 1992; Jorens and Schepens, 1993). Human and animal studies have provided evidence indicating that pentachlorophenol is metabolized to various conjugated metabolites. Both the parent compound and the conjugates are excreted in the urine (Braun et al., 1979).
Assessing the potential toxicity of technical (commercial) grade pentachlorophenol is complicated by the presence of the toxic impurities that are usually present, and the effects resulting from occupational exposure are often difficult to attribute to a specific route of exposure (Jorens and Schepens, 1993). The effects in humans following acute oral exposure include increased heart and respiratory rates, elevated temperature, increased basal metabolic rate, and death (29 and 401 mg/kg) (RTECS, 1989).
Human fatalities and toxic effects including tachycardia, jaundice, and other hematologic alterations have been reported for acute and subchronic occupational (e.g., sawmill workers, herbicide sprayers) inhalation exposures to pentachlorophenol. Upper respiratory tract inflammation and bronchitis were reported for sawmill workers chronically exposed to pentachlorophenol (Baader and Bauer, 1951; Menon et al., 1958; ATSDR, 1992). However, dose-terms for these exposures were not available, and concurrent exposures to other chemicals make definitive assessments impossible.
Data regarding the dermal exposure of humans to pentachlorophenol are anecdotal or equivocal, lack dose terms, and are compromised by concurrent exposures to other chemicals including the known contaminants in technical-grade pentachlorophenol. Acute exposure to 0.4% pentachlorophenol produced localized irritation (Bevenue et al., 1967), and subchronic exposures have caused chloracne (Baader and Bauer, 1951; O'Malley et al., 1990) and possibly renal damage (ATSDR, 1992). Dermal lesions including pemphigus and chronic urticaria have been reported for humans chronically exposed to pentachlorophenol-treated wood (Lambert et al., 1986). There currently are no definitive data regarding reproductive toxicity in humans exposed to pentachlorophenol.
Acute oral exposure of animals to pentachlorophenol affects the liver, kidneys, cardiovascular system, and the peripheral and central nervous system. Oral LD50 values for laboratory animals range from 27 to 230 mg/kg (Borzelleca et al., 1985; U.S. Air Force, 1989; ATSDR, 1992). Definitive data regarding the effects of subchronic or chronic oral exposure of humans to pentachlorophenol are not available. However, subchronic exposure (1 to 8 months) of rats to pentachlorophenol at doses ranging from 5 to 40 mg/kg/day has produced cardiovascular, hematotoxic, renal, hepatic, and immunologic responses (Schwetz et al., 1974, 1978; U.S. Air Force, 1989; ATSDR, 1992). Evidence of reproductive/developmental toxicity (increased resorptions, embryolethality, embryotoxicity, and teratogenicity) have also been observed in rats given pentachlorophenol during gestation (Larsen et al., 1974, 1976; Schwetz et al., 1978).
Because the most significant acute toxic effect of pentachlorophenol is elevated metabolism, a specific target organ or tissue is difficult to identify. However, for subchronic and chronic exposures, toxicity data indicate that the liver, kidney, and cardiovascular system are targets for some of the toxic effects of pentachlorophenol.
Both the chronic and subchronic RfDs for pentachlorophenol are 3.00E-02 mg/kg/day based on a NOAEL of 3 mg/kg/day and a LOAEL of 10 mg/kg/day for histopathologic findings in the liver and kidneys of rats given pentachlorophenol in the diet for 2 years (EPA, 1994; Schwetz et al., 1978).
The RfC for pentachlorophenol is under review (EPA, 1994a).
Based upon increased incidences of hepatocellular adenomas and carcinomas, adrenal medulla pheochromocytomas, malignant pheochromocytomas, and hemangiosarcomas/hemangiomas in mice, pentachlorophenol is classified by the EPA as a probable human carcinogen (Weight of Evidence Category B2) and has an oral slope factor of 1.2E-01 (mg/kg/day)-1 and an oral unit risk of 3.0E-06 (g/L)-1 (EPA, 1994). The potential carcinogenicity of pentachlorophenol following inhalation exposure has not been evaluated.
Pentachlorophenol (CAS No. 87-86-5) is a halogenated man-made organic chemical with a molecular weight of 266.35 and a chemical formula of C6HCl5O (Budavari et al. 1989). In its pure form it is a colorless or white powder (needle-like crystalline structure), but the crude product may be dark gray to brown in color (ATSDR, 1992). Pentachlorophenol has a boiling point of 309-310C, a melting point of 190-191C, a density of 1.978 g/mL (Budavari et al., 1989), and a vapor pressure of 0.00011 mm Hg (ATSDR, 1992). Pentachlorophenol is almost insoluble in water, freely soluble in alcohol and ether, and moderately soluble in benzene (Budavari et al., 1989).
Pentachlorophenol was previously used extensively as a biocide and is still in use as a wood preservative but this use is restricted to certified applicators (ATSDR, 1992; U.S. Air Force, 1989). Commercial pentachlorophenol preparations contain 85 to 99% pentachlorophenol and various impurities including tetrachlorophenol (4-12%), trichlorophenol (<0.1-10%), chlorinated phenoxyphenols (1-5%), and polychlorinated dibenzo-p-dioxins and dibenzofurans (<1%) (U.S. Air Force, 1989; Jorens and Schepens, 1993). The presence of these contaminants makes the assessment of toxicity difficult for technical grade pentachlorophenol (Williams, 1982).
The primary route of exposure for pentachlorophenol involves occupational settings although environmental exposure may be relevant in the vicinity of spills, waste sites, or around sites where the chemical had been applied as a biocide (EPA, 1984; ATSDR, 1992).
Data for both humans and animals have shown that pentachlorophenol is readily absorbed via oral and inhalation routes (ATSDR, 1992). Absorption efficiency for inhalation exposure appears to be in the range of 70 to 88% (Casarett et al., 1969). Absorption of pentachlorophenol following oral exposure has been shown to be rapid in humans; peak blood levels were attained within 4 hours with an absorption half-time of 1.3 hours (Braun et al., 1979). A summary of epidemiologic data revealed pentachlorophenol mean serum concentrations of 8.7 - 320 g/L for unexposed populations, 214 - 5140 g/L for occupational exposure, and 38 - 420 g/L for log-home residents (Jorens and Schepens, 1993). Animal data also indicated rapid and nearly complete absorption following oral exposure. Tests with human subjects have shown that the rate and extent of absorption of pentachlorophenol is dependent upon the vehicle; oil-based vehicles tend to provide greater and more rapid absorption than do aqueous vehicles (Horstman et al., 1989). Generally, absorption kinetics data for pentachlorophenol in humans are conflicting (Jorens and Schepens, 1993). No animal data are available regarding the dermal absorption of this chemical. However, dermal absorption in humans may be inferred from the occurrence of systemic toxic effects following dermal exposure (Robson et al., 1969).
Pentachlorophenol has been found in the testes, kidney, liver, and prostate in non-occupationally exposed individuals (Wagner et al., 1991). Uhl et al. (1986) noted extensive plasma protein binding of pentachlorophenol in exposed humans, and both in vivo and in vitro studies have shown that pentachlorophenol undergoes extensive binding with plasma proteins (Braun et al., 1977). In rats, pentachlorophenol is rapidly distributed to the liver and lungs following single inhalation exposures (ATSDR, 1992). These acute exposure experiments indicated that pentachlorophenol did not accumulate in the body. However, experiments examining tissue burden following long-term exposures are not available. Oral exposure of rats given radio-labeled pentachlorophenol also demonstrated rapid distribution with greater levels of radioactivity being detected in the liver and kidneys and lower levels occurring in the brain, adipose tissue, lungs, testes, ovaries, heart, and adrenal glands. The distribution of [14C]-pentachlorophenol in monkeys 360 hours after a single 10 mg/kg oral dose suggested extensive enterohepatic circulation; eighty percent of the 11% retained in the body at this time was found in the liver and small intestine (ATSDR, 1992).
Data from both human and animal studies indicate that pentachlorophenol is not extensively metabolized (ATSDR, 1992). It has been suggested that extensive plasma protein-binding may account, in part, for the limited metabolism. However, there is some evidence for hepatic metabolism to glucuronide conjugates and oxidative dechlorination to tetrachlorohydroquinone in both humans (Ahlborg et al., 1974; Braun et al., 1979) and animals (Ahlborg et al., 1974; Braun et al., 1977; Renner, 1989; Renner and Hopfer, 1990) following oral exposure. Ahlborg et al. (1974) reported unchanged parent compound and tetrachlorohydroquinone but no glucuronide conjugates in the urine of workers exposed via inhalation to pentachlorophenol. Braun et al. (1979) and Uhl et al. (1986), however, detected no tetrachlorohydroquinone in human volunteers given oral doses of pentachlorophenol, thereby implying exposure route-dependent variability in the metabolism of the chemical. Species variability in the metabolism of pentachlorophenol has also been reported by Braun and Sauerhoff (1976) who showed that unlike rats, monkeys given oral doses of pentachlorophenol excreted only parent compound and no tetrachlorohydroquinone.
Although most pentachlorophenol entering the body is eliminated unchanged in the urine, data regarding the excretion kinetics are not definitive. Excretion kinetics and metabolite profiles appear to be affected by route and duration of exposure (ATSDR, 1992). Bevenue et al. (1967) reported a biphasic elimination of pentachlorophenol in workers exposed to the chemical via inhalation; urinary pentachlorophenol levels decreased by 35% per day for the first two days followed by a slower rate of excretion. Casarett et al. (1969) reported excretion half-times of 10 hours for workers exposed for a single 45-minute inhalation exposure and nearly 18 days for workers experiencing long-term inhalation exposures. Animal studies are limited but also suggest that pentachlorophenol is excreted unchanged (ATSDR, 1992).
Human studies of pentachlorophenol excretion following oral exposure have yielded conflicting results. Braun et al. (1979) reported that pentachlorophenol was excreted in the urine as parent compound (74%) and as the glucuronide (12%) and that 4% of the dose was excreted in the feces as parent compound and the glucuronide. However, several investigators have indicated that pentachlorophenol is extensively metabolized to a glucuronide conjugate in humans (Uhl et al. 1986, Jorens and Schepens, 1993) A plasma elimination half-life of 30.2 hours and a urinary excretion half-life of 33.1 hours were reported for humans taking a single oral dose (0.1 mg/kg) of pentachlorophenol (Braun et al., 1979). These investigators also noted that excretion followed first-order kinetics with evidence of enterohepatic circulation of the chemical. Uhl et al. (1986), however, reported slow excretion (elimination half-life of 14 days in both plasma and urine) for humans ingesting 0.016 to 0.31 mg/kg. These investigators attributed the slow elimination to extensive plasma protein binding and renal tubular reabsorption. However, these studies also employed different dosing protocols (one using fasting subjects and the other having administered the chemical with no dietary restrictions) which may account for some of discrepancies in the results (ATSDR, 1992). A review of the findings from pentachlorophenol studies indicates considerable variability in the excretion kinetics (Jorens and Schepens, 1993).
Human oral LDlo values of 29 and 401 mg/kg are reported in RTECS (1989), and an LDlo of 1 g ( 17.0 mg/kg) was estimated by Driesbach (1980). The only other information regarding the acute toxicity of ingested pentachlorophenol is a case report of a suicide involving ingestion of the chemical (dose not reported) (Cretney, 1976).
Acute exposure to toxic levels of pentachlorophenol results in increased basal metabolic rate with a subsequent increase in body temperature, respiratory rate, and heart rate. Death is preceded by progressive neuromuscular weakness, convulsions, and cardiac arrest (Fielder et al., 1982; Clayton and Clayton, 1981).
Oral LD50 values are available for several animal species (rat, mouse, rabbit, hamster) and vary from 27 to 230 mg/kg. The interpretation of these values is, however, complicated by the fact that some tests employed pure pentachlorophenol while others used technical grade, pentachlorophenol in fuel oil, or various other vehicles (olive oil, water) (U.S. Air Force, 1989; ATSDR, 1992). Generally, lower toxicity values were obtained in those tests using organic solvent vehicles, probably the result of greater absorption of the lipid-soluble pentachlorophenol in the presence of these vehicles. Borzelleca et al. (1985) reported LD50 values of 177 and 117 mg/kg for gavage administration of pure pentachlorophenol in male and female mice, respectively. Similar values (129 and 134 mg/kg for males and females, respectively) were reported by Renner et al. (1986) using the pure chemical administered to mice.
Single doses in excess of 10 mg pentachlorophenol/kg body weight have been shown to cause an increase in liver weight in rats (Nishimura et al., 1982). McGavack et al. (1941) also showed degenerative changes in motor neurons and central nervous system congestion in rats given a single oral dose of 10% sodium pentachlorophenol. Deichmann et al. (1942) reported that acute oral exposure (doses not specified) of rats, rabbits, guinea pigs, and dogs caused extensive vascular damage.
Information regarding the toxicity of pentachlorophenol in humans following subchronic oral exposure is not available.
An LD50 of 300 mg/kg/day was determined for rats given pentachlorophenol twice weekly for 1 to 3 months (Nishimura et al., 1980). Cardiovascular, hematotoxic, renal, and hepatic effects have also been associated with subchronic oral exposure of rats to pentachlorophenol and are summarized in U.S. Air Force (1989) and ATSDR (1992). Most of these effects involved increases in organ weight and histopathological changes and occurred at doses ranging from 5 to 40 mg/kg/day and involved exposure durations ranging from 1 month to 8 months.
Immunological effects in rats exposed subchronically to pentachlorophenol have been characterized as decreased antibody response (0.5 mg/kg, 6-week exposure), depressed cellular immunity (15 mg/kg, 160-day exposure), and enhanced susceptibility to tumor growth (6.5 mg/kg, 10-12 weeks exposure) (Kerkvliet et al., 1985).
Information regarding the toxicity or pentachlorophenol in humans following chronic oral exposure is not available.
Animal data regarding the noncancer effects of chronic oral exposure to pentachlorophenol appear to be limited to studies with rats (U.S. Air Force, 1989; ATSDR, 1992). In a study by Schwetz et al. (1978), rats given Dowicide EC-7 (90% pentachlorophenol with lower levels of dioxins and dibenzofurans than most technical grade pentachlorophenol preparations) in the diet for 24 months exhibited some signs of hepatotoxicity (elevated serum enzyme levels, histopathological alterations) at a dose level of 30 mg/kg/day. Increased kidney weights and a dose-related increase in kidney discoloration were also observed at doses of 1 to 30 mg/kg/day, and a 12% decrease in body weight gain was noted in both male and female rats in the 30 mg/kg/day dose group. Data from this study provided the basis of a NOAEL and LOAEL of 3 and 10 mg/kg/day, respectively, used for deriving the oral RfD.
No information is available regarding the developmental or reproductive toxicity of pentachlorophenol in humans following oral exposure.
Two studies by Schwetz et al. (1974, 1978) examined the reproductive/developmental effects of pentachlorophenol in rats. In the 1974 study, rats were given 5, 15, 30, or 50 mg/kg/day of pure pentachlorophenol (>98%) or 5.8, 15, 34.7, or 50 mg/kg/day of commercial grade pentachlorophenol (88.4%) by gavage on gestation days 6-15. An increased incidence of resorptions was observed in rats given pure chemical (98 and 100% for 15 and 30 mg/kg/groups, respectively) or commercial grade pentachlorophenol (9, 27, and 58% for the 15, 34.7, and 50 mg/kg/ groups, respectively). Doses of 5 or 15 mg/kg/day (pure chemical) or 15 mg/kg/day (commercial grade) produced no observable effects. At doses of 50 mg/kg/day on days 8-11, 12-15, or 6-15, developmental effects were observed that included embryolethality and embryotoxicity (with depression of maternal body weight) for both grades of pentachlorophenol although the pure grade appeared to be somewhat more toxic. At 15 mg/kg/day, both forms produced skeletal abnormalities (lumbar spurs, supernumary ribs). At 5 mg/kg/day, the purified form produced a significantly increased incidence of delayed ossification of skull bones. In the study by Schwetz et al. (1978), exposure of male and female rats to pure pentachlorophenol (30 mg/kg/day) 62 days prior to and during mating, and throughout gestation and lactation, resulted in a decreased mean body weight in the adult rats and a significantly increased incidence of skeletal aberrations in offspring. At 3 mg/kg/day, there were no apparent adverse effects on the fetuses or dams.
Evidence of pentachlorophenol-induced teratogenicity in rats was also reported by Larsen (1976) and Larsen et al. (1975). Malformations (exencephaly, microphthalmia, and absent tail) were observed following exposure of dams to a single 60 mg/kg dose on day 9 of gestation. Additionally, dwarfism was observed in a fetus following exposure of the dam to the same dose but on day 8 of gestation. Treatment on day 9 or 10 resulted in significant (p<0.05) reduction of fetal weight gain (20 and 13%, respectively). All of these effects were at a dose that was maternally toxic.
ORAL RfDs: 3.00E-02 (EPA, 1994b)
UNCERTAINTY FACTOR: 100
NOAEL: 3 mg/kg/day
LOAEL: 10 mg/kg/day
ORAL RfDc: 3.00E-02 mg/kg/day (EPA, 1994a)
UNCERTAINTY FACTOR: 100
MODIFYING FACTOR: 1
NOAEL: 3 mg/kg/day
LOAEL: 10 mg/kg/day
Data base: medium
VERIFICATION DATE: 05/20/85
PRINCIPAL STUDY: Schwetz et al., 1978
COMMENTS: The RfD is based on histopathological alterations in the liver and kidney of rats given dietary pentachlorophenol for 2 years. The chronic RfD has been adopted as the subchronic RfD.
Fatalities in humans following acute inhalation exposure to pentachlorophenol have been reported, but it is difficult to attribute the effect to pentachlorophenol because of concurrent exposure to other chemicals (Menon, 1958). In all cases, exposures were occupational (herbicide sprayers and sawmill workers) and may have also involved dermal exposure. Exposure concentrations were not available for these incidences.
Cardiovascular (tachycardia), hepatic (jaundice), and hematological effects (hemolytic anemia, lowered leukocyte counts and lowered hematocrit) have been reported in humans following acute exposures to pentachlorophenol-containing pesticides (ATSDR, 1992). However, no dose or exposure terms are available and these exposures involved complex mixtures or simultaneous exposure to other chemicals. Therefore, the effects cannot necessarily be attributed to pentachlorophenol.
A 45-minute LC50 of 14 mg/m3 was reported for rats exposed to an aerosol of sodium pentachlorophenol (equivalent to 11.7 mg/kg) (Hoben et al., 1976). No additional information is available regarding the effects of acute inhalation exposure of animals to pentachlorophenol.
Nine deaths over an 18-month period were reported for sawmill workers possibly exposed to pentachlorophenol. However, data regarding exposure concentrations or duration are not available, and simultaneous exposures to other chemicals could not be eliminated as possible causative factors. Baader and Bauer (1951) reported severe bronchitis in seven pentachlorophenol production workers who had been in contact with the chemical for 5 to 10 months.
No information was available regarding the toxic effects of pentachlorophenol in animals following subchronic inhalation exposure.
Chronic inhalation exposure of humans to pentachlorophenol has been associated with inflammation of the upper respiratory tract and bronchitis (Baader and Bauer, 1951; Klemmer et al., 1980) and with renal effects characterized by reduced glomerular filtration rate and altered tubular function (Begley et al., 1977). The renal effects were associated with blood pentachlorophenol levels of 5.1 ppm and subsided following removal from exposure. Specific information regarding the exposure levels and duration of these occupational exposures was not provided. Furthermore, the exposures involved commercial-grade pentachlorophenol as well as concurrent exposure to other chemicals.
No information was available regarding the toxic effects of pentachlorophenol in animals following chronic inhalation exposure.
Definitive data regarding the reproductive and developmental toxicity of pentachlorophenol in humans following inhalation exposure is not available.
Definitive data regarding the reproductive and developmental toxicity of pentachlorophenol in animals following inhalation exposure is not available.
The RfC for pentachlorophenol is under review by the EPA work group (EPA, 1994a).
Information on the toxic effects of acute dermal exposure in humans is limited to an anecdotal report of transient localized redness and pain following immersion of the hands in a solution of 0.4% pentachlorophenol for 10 minutes (Bevenue et al., 1967).
Single dermal applications of 10% pentachlorophenol (60-600 mg/kg) to rabbits resulted in pronounced edema and inflammation leading to desquamation and hair loss (McGavack et al., 1941; Deichmann et al., 1942). No additional information is available regarding the effects of acute dermal exposure of animals to pentachlorophenol.
Dermal exposure of humans to commercial-grade pentachlorophenol may cause chloracne. Baader and Bauer (1951) reported this condition in 10 pentachlorophenol production workers who had been potentially exposed for 5 to 10 months. Based on the incidence noted in company medical records, O'Malley et al. (1990) reported that chloracne occurred in 47 of 648 (7%) pentachlorophenol production workers exposed for an average of 1.4 years. However, because of confounding factors (contaminants, discrepancies in diagnosis and records), these findings are equivocal. Short-term dermal exposure to commercial-grade pentachlorophenol has been implicated in renal toxicity, but the findings are equivocal because of the toxic contaminants (dioxins and dibenzofurans) known to occur in the commercial-grade product and also because of the distinct possibility of simultaneous inhalation exposure to the pentachlorophenol (ATSDR, 1992). Tachycardia, respiratory distress, and liver changes (not specified) were reported for 20 infants exposed to pentachlorophenol used in laundering diapers and bed linen (Robson et al., 1969). Two of the infants died and exhibited hepatic and renal degeneration.
The only animal data available regarding the effects of subchronic dermal exposure to pentachlorophenol is a report of fatalities in rabbits following dermal application (6-61 weeks) of 4% pentachlorophenol in fuel oil by Deichmann et al. (1942). These data are, however, equivocal because of the confounding effect of the potential toxicity of the fuel oil.
Skin disorders such as pemphigus vulgaris and chronic urticaria have been reported for individuals chronically exposed to pentachlorophenol-treated wood (Lambert et al., 1986), and various other anecdotal reports of dermal lesions have been summarized in ATSDR (1992). Like much of the other toxicological data on pentachlorophenol, the effect of chemical contaminants in the commercial grade product may be responsible for some of the observed effects.
Definitive data regarding the developmental effects in humans or animals following dermal exposure to pentachlorophenol are not available.
A proposed mechanism of action for pentachlorophenol is the uncoupling of oxidative phosphorylation resulting in accelerated aerobic metabolism that causes increased heat production. This hypermetabolic state may result in hyperthermia, tachycardia, tachypnea, diaphoresis, hyperemia, metabolic acidosis, and death. Regarding this mechanism, therefore, no single organ or tissue is specifically targeted but several may exhibit signs of toxicity as indicated in the following list.
1. Liver: Both technical grade and pure pentachlorophenol appear to induce toxic effects in the liver of animals exposed subchronically to doses ranging from 1-30 mg/kg/day.
2. Cardiovascular System: Acute oral exposure to pentachlorophenol may induce tachycardia in humans and cause extensive vascular damage in animals.
3. Kidney: Pentachlorophenol has been shown to cause histopathologic and functional alterations in the kidneys of animals following 24-month exposure at 30 mg/kg/day.
4. Nervous System: Degenerative changes in motorneurons have been reported for rats given single oral doses of 10% sodium pentachlorophenol.
1. Reproductive/Developmental: Studies in rats have demonstrated that gestational exposure to pentachlorophenol produced increased embryolethality, embryotoxicity, teratogenic and developmental effects (50 mg/kg) and increased resorptions (15-50 mg/kg).
2. Immune System: Decreased immune response was observed in rats following subchronic exposure to pentachlorophenol at doses of 0.5 mg/kg for 6 weeks or 15 mg/kg for 160 days.
1. Respiratory tract: Inflammation of the upper respiratory tract and bronchitis have been reported for chronic exposure of humans to pentachlorophenol.
2. Cardiovascular system: Alterations in cardiac function (tachycardia) have been reported for humans following acute exposures (dose/exposure terms not available) to pentachlorophenol.
3. Kidney: Altered glomerular filtration rate and renal tubule dysfunction in humans have been associated with chronic exposure to pentachlorophenol producing blood concentrations of 5.1 ppm.
Similar to oral exposure, pentachlorophenol may produce a febrile condition possibly due to an uncoupling of oxidative phosphorylation in tissues. The resulting adverse effects from this hypermetabolic state are not necessarily the result of an effect on any one specific tissue or organ.
Studies assessing the potential carcinogenicity of pentachlorophenol in humans are not available.
Several studies have examined the potential tumorigenicity of technical-grade pentachlorophenol in animals. Innes et al. (1969) found no statistically significant increase in tumor incidences in two strains of hybrid C57BL mice given the chemical by gavage at doses of 46.4 mg/kg on days 7-28 of age and in the diet at a dose of 130 mg/kg up to 18 months of age. Negative findings were also reported for Sprague-Dawley rats given pure pentachlorophenol (up to 30 mg/kg) in the diet for 22-24 months (Schwetz et al., 1978). However, results of an NTP bioassay (NTP, 1989) provided evidence of carcinogenicity in mice (B6C3F1, 50 mice/sex/dose group, 30 mice/sex/control group) given technical-grade pentachlorophenol (100 or 200 ppm) or Dowicide EC-7 (100, 200, or 600 ppm), a commercial preparation with lower levels of dioxin and dibenzofuran contaminants, in their feed for 2 years. The investigators concluded that under the conditions of the study, there was clear evidence of carcinogenic activity (hepatocellular adenomas and carcinomas, adrenal medullary pheochromocytomas) in male mice fed technical-grade pentachlorophenol and for mice of both sexes given dietary Dowicide EC-7 (hemangiosarcomas).
Epidemiologic studies have not provided evidence indicating that pentachlorophenol is a human carcinogen following inhalation exposure. The few available studies are limited by various confounding factors (concurrent exposure to other potential carcinogens, inadequate sample size and follow-up periods, competing causes of death, and brief exposure periods).
No information is available regarding the potential carcinogenicity of pentachlorophenol in animals following inhalation exposure.
No information is available suggesting that pentachlorophenol is carcinogenic by other routes of exposure.
The EPA has placed pentachlorophenol in Weight of Evidence Group B2; probable human carcinogen. This classification is based on inadequate human data and statistically significant increases in the incidences of multiple biologically significant tumor types (hepatocellular adenomas and carcinomas, adrenal medulla pheochromocytomas and malignant pheochromocytomas, and/or hemangiosarcomas and hemangiomas) in one or both sexes of B6C3F1 mice using two different preparations of pentachlorophenol (NTP, 1989).
SLOPE FACTOR: 1.20E-01 (mg/kg/day)-1 (EPA, 1994a)
UNIT RISK 3.0E-06 (g/L)-1 (EPA, 1994a)
VERIFICATION DATE: 08/20/90
UNIT RISK: 3.00E-06 (g/L)-1
COMMENT: The slope factor is based on increased tumor incidences in male and female B6C3F1 mice following dietary exposure to two different pentachlorophenol preparations (NTP, 1989)
Ahlborg, U. G., J. E. Lindgren and M. Mercier. 1974. Metabolism of pentachlorophenol. Arch. Toxicol. 32: 271-281. (cited in ATSDR, 1992)
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Baader, E. W. and H. J. Bauer. 1951. Industrial intoxication due to pentachlorophenol. Ind. Med. Surg. 20: 286-290. (cited in ATSDR, 1992)
Begley, J., A. W. Reichert, A. W. Seismen, et al. 1977. Association between renal function tests and pentachlorophenol exposure. Clin. Toxicol. 11: 97-106. (cited in ATSDR, 1992)
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Braun, W. H., J. D. Young, G.E. Blau, et al. 1977. The pharmacokinetics of pentachlorophenol in rats. Toxicol. Appl. Pharmacol. 41: 395-406. (cited in ATSDR, 1992)
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Casarett, L. J., A. Bevenue, W. L. Yauger, et al. 1969. Observations on pentachlorophenol in human blood and urine. Am. Ind. Hyg. Assoc. J. 30: 360-366. (cited in ATSDR, 1992)
Clayton, G. D. and F. E. Clayton, Eds. 1981. Patty's Industrial Hygiene and Toxicology, 3rd ed. New York: John Wiley and Sons, Inc.
Cretney, M. J. 1976. Pentachlorophenol death. Bull. TIAFT 12: 10. (cited in ATSDR, 1992)
Deichmann, W., W. Machle, K. V. Kitzmiller, et al. 1942. Acute and chronic effects of pentachlorophenol and sodium pentachlorophenate upon experimental animals. J. Pharmacol. Exp. Ther. 76: 104-117. (cited in ATSDR, 1992)
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