National Toxicology Program

Selected toxicity information from HSDB, one of the National Library of Medicine's databases. ¹

Names (NTP)

• Pentachlorophenol, Dowicide EC-7
• Pentachlorophenol, DP-2
• Pentachlorophenol, purified
• Pentachlorophenol, technical
• PENTACHLOROPHENOL (TRANSGENIC LECM)
• TRANSGENIC-LABORATORY OF ENVIRONMENTAL CARCINOGENESIS & MUTAGENESIS (PENTACHLOROPHENOL)
• Transgenic LECM (Pentachlorophenol)

Human Toxicity Excerpts

• INGESTION CAUSES INCR THEN DECR OF RESP, BLOOD PRESSURE, URINARY OUTPUT; FEVER; INCR BOWEL ACTION; MOTOR WEAKNESS, COLLAPSE WITH CONVULSIONS & DEATH. CAUSES LUNG, LIVER, KIDNEY DAMAGE; CONTACT DERMATITIS. ... DUST CAUSES SNEEZING. [The Merck Index. 10th ed. Rahway, New Jersey: Merck Co., Inc., 1983., p. 1021]**PEER REVIEWED**
  
• MOST IMPORTANT EFFECT OF PENTACHLOROPHENOL INHALATION IS ACUTE POISONING CENTERING IN CIRCULATORY SYSTEM WITH ACCOMPANYING HEART FAILURE. ... DUSTS ARE PARTICULARLY IRRITATING TO EYES & NOSE IN CONCN GREATER THAN 1 MG/CU M. SOME IRRITATION OF NOSE MAY OCCUR AT 0.3 MG/CU M. ... SURVIVORS OF ... INTOXICATION SUFFER ... VISUAL DAMAGE & ACUTE TYPE OF SCOTOMA. OTHER DAMAGE INCL ACUTE INFLAMMATION OF CONJUNCTIVA & CHARACTERISTICALLY SHAPED CORNEAL OPACITY, CORNEAL NUMBNESS & SLIGHT MYDRIASIS. [American Conference of Governmental Industrial Hygienists. Documentation of the Threshold Limit Values and Biological Exposure Indices. 5th ed. Cincinnati, OH: American Conference of Governmental Industrial Hygienists, 1986., p. 461]**PEER REVIEWED**
  
• Immersion of hands for 10 min in a 0.4% soln caused pain and inflammation. [USEPA; Ambient Water Quality Criteria Doc: Pentachlorophenol p.C-20 (1980) EPA 440/5-80-065]**PEER REVIEWED**
  
• Dust and mist concn greater than 1.0 mg/cu m resulted in painful irritation of upper respiratory tract in persons not previously exposed to pentachlorophenol. Violent sneezing and coughing accompanied exposure. Conditioned persons tolerated concn up to 2.4 mg/cu m. [USEPA; Ambient Water Quality Criteria Doc: Pentachlorophenol p.C-20 (1980) EPA 440/5-80-065]**PEER REVIEWED**
  
• Chronic exposure in workers resulted in elevated bilirubin and creatine phosphokinase. Higher prevalence of gamma mobility c-reactive protein in sera. [USEPA; Ambient Water Quality Criteria Doc: Pentachlorophenol p.C-23 (1980) EPA 440/5-80-065]**PEER REVIEWED**
  
• Five cases of pentachlorophenol poisoning, including 2 fatalities, occurred in two small wood preservative plants ... fever ... severe hyperpyrexia ... increased anion gap and renal insufficiency. ... Pentachlorophenol may uncouple oxidative phosphorylation, resulting in a poisoning syndrome characterized by hyperpyrexia, diaphoresis, tachycardia, tachypnea, abdominal pain, nausea and even death. [Wood S et al; J Occup Med 25 (7): 527-530 (1983)]**PEER REVIEWED**
  
• Repeated exposure to commercial (technical grade) pentachlorophenol preceded aplastic anemia in four patients and pure red cell aplasia in two. Two patients developed concomitant or subsequent Hodgkin's disease and acute leukemia ... . [Roberts HJ; South Med J 76 (1): 45-8 (1983)]**PEER REVIEWED**
  
• Chromosome analyses were carried out on peripheral lymphocytes from 22 male workers employed at a pentachlorophenol producing factory. ... A small but significant increase in the frequency of dicentrics and acentrics was observed. ... [Bauchinger M et al; Mutat Res 102 (1): 83-8 (1982)]**PEER REVIEWED**
  
• Workers (3 women, 15 men) in a pentachlorophenol processing factory, with a mean activity of processing pentachlorophenol for 12 years were studied. ... Pentachlorophenol levels in plasma ranged from 0.02-1.5 ug/l, median 0.25 ug/l, and in urine 13-1224 ug/l, median 112 ug/l or 11-2111 ug/g creatinine, median 111 ug/g creatinine. ... Individual evaluation of the toxicological and neurophysiological results gave /indications/ that in some cases decreased nerve conduction velocity was caused by chronic exposure to pentachlorophenol. [Triebig G et al; Int Arch Occup Environ Health 48 (4): 357-68 (1981)]**PEER REVIEWED**
  
• A cytogenetic study was performed on 20 healthy workers exposed to pentachlorophenol in concentrations ranging from 1.2 to 180 ug/cu m (maximum concentration at the workplace is 500 ug/cu m) for 3 to 34 years. Pentachlorophenol was determined in the blood plasma of all probands, yielding concentrations between 23 and 775 ug/l (Biological Tolerance Value is 1000 ug/l). In vitro pentachlorophenol up to 90 mg/l was added to phytohemagglutinin-stimulated lymphocytes of normal healthydonors without any effect on sister chromatid exchange or chromosomal aberrations, whereas a slow down of cell proliferation could be detected in the presence of 60 mg pentachlorophenol/l. [Ziemsen B et al; Int Arch Occup Environ Health 59: 413-7 (1987)]**PEER REVIEWED**
  
• A series of studies of chronically exposed workers has been conducted in Hawaii. The first involved workers in wood treatment plants & farmers or pest-control operators. Elevation of serum enzyme levels, ie, serum glutamic-oxaloacetic transaminase, serum glutamic pyruvic transaminase, & lactic dehydrogenase, & low-grade infections or inflammations of the skin, eye, & respiratory tract were found in the exposed groups. In a /separate/ study, plasma protein levels were found to be elevated in exposed, as compared with unexposed, workers. [National Research Council. Drinking Water and Health, Volume 6. Washington, D.C.: National Academy Press, 1986., p. 388]**PEER REVIEWED**
  
• ALTHOUGH PENTACHLOROPHENOL IS HIGHLY TOXIC IN ITS OWN RIGHT, SOME STUDIES SUGGEST THAT CONTAMINANTS MAY BE RESPONSIBLE FOR /SRP: SOME OF THE POISONOUS POTENTIAL OF/ THE TECHNICAL GRADE. COMPARISON OF EFFECTS OF TECHNICAL VERSUS PURIFIED PCP INDICATED THAT ONLY TECHNICAL GRADE PRODUCED CHLORACNE, CHICK EDEMA, HEPATIC PORPHYRIA & INCR RELATIVE LIVER WT. TECHNICAL GRADE WAS ALSO MUCH MORE ACTIVE AS LIVER ENZYME INDUCER. [Doull, J., C.D.Klassen, and M.D. Amdur (eds.). Casarett and Doull's Toxicology. 3rd ed., New York: Macmillan Co., Inc., 1986., p. 561]**PEER REVIEWED**
  
• NRC Safe Drinking Water Committee: ... noted that the toxicity of pentachlorophenol is increased by impurities contained in the technical product. For example, the No Observed Effect Level for pure pentachlorophenol is 3 mg/kg/day; however, the No Observed Effect Level for technical pentachlorophenol is 1 mg/kg/day, indicating increased toxicity due to impurities. [National Research Council. Drinking Water and Health, Volume 6. Washington, D.C.: National Academy Press, 1986., p. 396]**PEER REVIEWED**
  
• The general population is more susceptible during hot weather. [Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. DHHS(NIOSH) Publication No. 81-123 (3 VOLS). Washington, DC: U.S. Government Printing Office, Jan. 1981., p. 1]**PEER REVIEWED**
  
• Individuals emptying bags of prilled (granular) or powder formulations of pentachlorophenol and of sodium pentachlorophenol are at an incr oncogenic risk. [USEPA; Wood Preservatives Position Doc 2/3: Creosote, Inorganic Arsenicals, Pentachlorophenol p.587 (1981) EPA 341-085/4643]**PEER REVIEWED**
  
• SEVERAL AREAS IN PENTACHLORPHENOL TOXICOLOGICAL PROFILE, SUCH AS CARCINOGENESIS & MUTAGENESIS, ARE NOT COMPLETE. WITH REGARD TO OCCUPATIONAL EXPOSURES, PRECAUTIONS SHOULD BE TAKEN TO AVOID DIRECT CONTACT & AIR LEVELS SHOULD BE KEPT WITHIN ACCEPTABLE LEVELS. [WILLIAMS PL; PENTACHLOROPHENOL; AM IND HYG ASSOC J 43 (11): 799-810 (1982)]**PEER REVIEWED**
  
• A case of a 33 yr old man who died following occupational exposure to pentachlorophenol is presented. Postmortem examination revealed cerebral edema and fatty degeneration of the viscera. [Gray RE et al; Arch Environ Health 40 (3): 161-4 (1988)]**PEER REVIEWED**
  
• A longitudinal study was performed to examine whether chronic occupational exposure to pentachlorophenol or its compounds causes measurable alterations in the conduction velocity in peripheral nerves as an adverse effect. In total, the results of nerve conduction velocity determinations in 1980 and 1984 in 10 subjects (7 men, 3 women) who had been exposed for an average of 16 years (range 4-24) were available. The concentrations of pentachlorophenol in the air at the workplace varied between 0.3 and 180 ug/cu m and were thus below the maximum allowed concn (MAK value) of 500 ug/cu m. The biological monitoring carried out showed the following results: pentachlorophenol in the serum: 38-1270 ug/l; pentachlorophenol in urine 8-1224 ug/l. Compared with the upper normal limits pentachlorophenol in the serum 150 ug/l, pentachlorophenol in the urine 60 ug/l), distinct internal exposure to pentachlorophenol has resulted in some of the employees. Determinations of the nerve conduction velocity of motor and sensory nerve fibers (ulnar, median, peroneal, and sural nerve) were always in the normal range. A significant difference in the nerve conduction velocity for the period 1980-4 could not be detected. In addition, the correlation analyses did not show any hints of dose-effect relations. It is concluded that occupational exposure to pentachlorophenol over several years in the concentrations observed probably do not lead to any adverse effects on the peripheral nervous system. [Triebig G et al; Br J Ind Med 44 (9): 638-41 (1987)]**PEER REVIEWED**
  
• Three case reports of skin lesions associated with exposure to pentachlorophenol in wood preservatives were described. Since pentachlorophenol and its sodium salt are commonly used in wood preservatives, paints, and disinfectants due to their fungicidal, insecticidal, bactericidal, herbicidal, and molluscicidal properties, exposure can occur in both occupational and non-occupational settings. The cases described involved two males and one female, all of whom were caucasian. Serum pentachlorophenol levels were measured in each individual. In non-exposed individuals, normal levels did not exceed 15 ug/l. The first case was that of a 41 year old man diagonosed as having pemphigus vulgaris. Exposure was attributed to a bookcase which had been treated with pentachlorophenol. Serum levels of pentachlorophenol varied from 10 to 47 ug/l in this patient, and clinical improvement was associated with decreased serum levels. A 28 year old female also diagnosed as having pemphigus vulgaris. Exposure in this case was ascribed to rafters in her home which had been treated with pentachlorophenol. Serum pentachlorophenol levels ranged from 10.8 to 114 ug/l, and also tended to decline with periods of clinical improvement. The third case was that of a 35 year old male who suffered from urticaria. Exosure in this case occurred when the patient had treated wood framework. Serum pentachlorophenol levels varied from 20.9 to 96 ug/1 in this individual. The role of pentachlorophenol in the pathogenesis of these cases is not understood. The ... possible mechanisms could include direct toxic effects, photoreactivity, or induced changes in epidermal immunology. [Lambert J et al; Acta Dermato-Venerolog 66 (2): 170-2 (1986)]**PEER REVIEWED**
  
• A 32 year old white male was seen at a university dermatology clinic complaining of an acneform eruption of 6 months duration. The patient was part owner of a firm that constructed piers for small boat marinas. The lumber used was pretreated with pentachlorophenol. Within about 9 months after beginning work, he noted a papular acneform eruption that occurred over the entire body. The eruption was characterized by multiple, small yellow/white papules. Areas most involved included the malar regions of the face, post auricular area, the trunk, buttocks, thighs, and lower legs. Some of papules were inflamed. A trephine punch biopsy of one of the papules showed a small epithelial lined cystic structure that communicated with the surface. The lining epithelium was composed of atrophic, but normal appearing, epidermis. Contained within the cyst was keratin-like material. The condition was diagnosed as chloracne. The patient's condition improved after 6 weeks oral treatment with isoretinoin. The patient remained asymptomatic for the ensuing 2 years of observation. The patient returned to work wearing appropriate protective clothing. A sample of pentachlorophenol used by the firm and samples of treated wood were analyzed for octachlorodibenzodioxin. Samples from the surface of the lumber contained about ten to 40 times the amount of octachlorodibenzodioxin as did the wood itself. The undiluted pentachlorophenol contained 1600 ppm octachlorodibenzodioxin. It was concluded the patient developed chloracne after exposure to pentachlorophenol treated lumber. The octachlorodibenzodioxin containing surface residue seemed to be the major source of the intoxication. [Cole GW et al; Contact Dermatitis 15 (3): 164-8 (1986)]**PEER REVIEWED**
  
• ... Liquid or solid causes smarting of skin and first-degree burns on short exposure; may cause secondary burns on long exposure. [U.S. Coast Guard, Department of Transportation. CHRIS - Hazardous Chemical Data. Volume II. Washington, D.C.: U.S. Government Printing Office, 1984-5., p. ]**PEER REVIEWED**
  
• The most important effect of pentachlorophenol inhalation is acute poisoning centering in the circulatory system with accompanying heart failure. [American Conference of Governmental Industrial Hygienists. Documentation of the Threshold Limit Values and Biological Exposure Indices. 5th ed. Cincinnati, OH: American Conference of Governmental Industrial Hygienists, 1986., p. 461]**PEER REVIEWED**
  
• Industrial hygiene experience shows that pentachlorophenol and its sodium salt are capable of inducing discomfort and local as well as systemic effects. Dusts are particularly irritating to the eyes and nose in concentrations greater than 1 mg/cu m. Some irritation of the nose may occur at 0.3 mg/cu m. Hardened workers can tolerate up to 2.4 mg/cu m. Pentachlorophenol is highly poisonous with a wide range of acute action but no pronounced cumulative properties. [American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 1178]**PEER REVIEWED**
  
• The survivors of pentachlorophenol intoxication suffer with impairments in autonomic function, circulation, visual damage, and an acute type of scotoma. Other damage included acute inflammation of the conjunctiva and characteristically shaped corneal opacity, corneal numbness, and slight mydriasis. Other symptoms involve excessive sweating, tachycardia, tachypnea, respiratory distress, hepatic enlargement, and metabolic acidosis. [American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 1179]**PEER REVIEWED**
  
• Symptoms of overexposure include an increase followed by a decrease in respiration, blood pressure, and urinary output; fever; increase in bowel action; motor weakness; and collapse with convulsions and death. [Fire Protection Guide to Hazardous Materials. 12 ed. Quincy, MA: National Fire Protection Association, 1997., p. 49-101]**QC REVIEWED**
  
• Chlorophenols appear to be mildly hepatotoxic, and studies in animals indicate that pentachlorophenol may reduce humoral and cell-mediated immunity as well as act as a cocarcinogen. /Chlorophenols/ [Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988., p. 1099]**PEER REVIEWED**
  
• Evaluation of lymphocyte phenotype frequencies, functional responses, serum immunoglobulin levels, and autoantibodies was completed for 38 individuals (ie, 10 families) who were exposed to pentachlorophenol in manufacturer treated log houses. Comparison of subjects with controls revealed that the exposed individuals had activated T cells, autoimmunity, functional immunosuppression, and B cell dysregulation. Autoimmunity was evidenced by elevation of TA1 phenotype frequencies and a 21% incidence of anti-smooth muscle antibody. Functional immunosuppression was evidenced by the significantly reduced responses to all mitogens tested and to allogeneic lymphocytes in the mixed lymphocyte culture test. There was a significant elevation of CD10, and an 18% increase or decrease in serum immunoglobulins was noted. A striking anomaly was the enhanced natural killer activity found in exposed females but not in males. [Mcconnachie PR, Zahalsky AC; Arch Environ Health 46 (4): 249-53 (1991)]**PEER REVIEWED**
  
• A mortality study was conducted in a cohort of 2283 plywood mill workers employed for at least one year between 1945 and 1955 in this industry. There were 570 deaths in this cohort, which was only 74% of the number expected based on comparable US mortality figures. A statistically nonsignificant excess of deaths was observed for lymphatic and hematopoietic cancer excluding leukemia (standard mortality ratio (SRM)=156). The greatest excess was for multiple myeloma (SRM=333). The excess mortality due to lymphatic and hematopoietic cancer excluding leukemia was highest after 20 yr duration of employment and latency. The workers were potentially exposed to formaldehyde, but there were no deaths due to nasal cancer. A subcohort of 818 workers involved in drying or gluing operations and exposed to formaldehyde and pentachlorophenol was also studied. Based on small numbers, statistically nonsignificant increased risks of death from Hodgkin's disease (SRM=333) and lymphosarcoma (SRM=250) were observed. The authors recommend further surveillance of the plywood mill worker cohort. [Robinson CF et al; NIOSH; Plywood Mill Workers' Mortality Patterns 1945-77 (Revised) (1987)]**PEER REVIEWED**
  
• The occurrence of chloracne among pentachlorophenol (PCP) workers was evaluated, and the risk of chloracne among workers who had records of direct skin contact with PCP was assessed. The workers had been employed at a facility which had produced PCP from 1938 through 1978. Of the 926 hourly workers in the study cohort, 666 had medical records available and were employed in 1953 or later; 65 had a diagnosis of chloracne, of which 47 were thought to be associated with PCP. The increase in duration of exposure did not appear to be related to the increased risk of chloracne. Episodes of direct skin contact with PCP were reported throughout the history of the facility. The workers with independent records of direct skin exposure had overall a four fold increase in the risk of developing chloracne compared with workers who did not have records of direct skin contact. Eight of the 13 cases had only one episode of direct skin contact with PCP prior to the diagnosis of chloracne, three cases had two episodes, and two cases had three episodes. The interval between the latest episode of direct skin contact and the diagnosis of chloracne for these 13 cases ranged from about 7 weeks to about 14 years. Four of the 13 cases occurred within 6 months of contact, four occurred between 1 and 2 years after the skin contact. Two occurred between 2 and 3 years after contact and three occurred more than 10 years after exposure. The authors conclude that exposure to PCP contaminated with hexachlorinated, heptachlorinated, and octachlorinated dibenzo-p-dioxins and dibenzofurans was associated with the occurrence of chloracne. [O'Malley MA et al; American Journal of Industrial Medicine 17 (4): 411-21 (1990)]**PEER REVIEWED**
  
• Pentachlorophenol (PCP) and its sodium salt are frequently used in wood preservatives. Little is known about the effects on man when being chronically exposed. Only vague skin symptoms, such as rashes, acne and cutaneous infections were described. We present two cases of pemphigus vulgaris with a known non-occupational chronic PCP exposure. The clinical course and the titer of pemphigus antibodies roughly correlate with the PCP levels in serum. In one case of chronic urticaria the exacerbations also run parallel to the PCP serum levels and increased anti-skin antibodies, without any manifestation of pemphigus vulgaris. The role of PCP as one of the causes provoking pemphigus vulgaris and chronic urticaria with raised anti-skin antibodies is discussed. [Lambert J et al; Acta Derm Venereol 66 (2): 170-2 (1986)]**PEER REVIEWED**
  
• A cytogenetic study was performed on 20 healthy workers exposed to pentachlorophenol (PCP) in concentrations ranging from 1.2 to 180 ug/cu m (Maximum Concentration at the workplace is 500 ug/cu m) for 3 to 34 years. PCP was determined in the blood plasma of all probands, yielding concentrations between 23 and 775 ug/l (Biological Tolerance Value is 1000 ug/l). In vitro PCP up to 90 mg/l was added to phytohaemagglutinin stimulated lymphocytes of normal healthy donors without any effect on sister chromatid exchange (SCE) or chromosomal aberrations (CA), whereas a slowdown of cell proliferation could be detected in the presence of 60 mg PCP/l. In vivo we neither observed a relation between PCP concentrations and the number of SCE nor an increase of CA. [Ziemsen B et al; Int Arch Occup Environ Health 59 (4) 413-7 (1987)]**PEER REVIEWED**
  
• Aplastic anemia, pure red cell aplasia, leukemia, lymphoma and other hematologic disorders have followed exposure to products containing the pesticide pentachlorophenol (PCP). Information in a 25-year compilation of documented case reports is summarized, involving industrial and home exposure and accidental poisoning in a nursery. The potential hematologic, mutagenic and carcinogenic effects of PCP and its dioxin-dibenzofuran contaminants also are reviewed. Owing to widespread contamination of the environment by PCP products, and latent periods of up to several decades after exposure before these disorders become manifest clinically, it is necessary to consider their etiologic or contributory role. These issues continue to surface in toxic tort litigation relative to causation. [Roberts HJ; J Fla Med Assoc 77 (2): 86-90 (1990)]**PEER REVIEWED**
  
• Pentachlorophenol (PCP) is a substance whose widespread use, mainly in wood protection and pulp and paper mills, has led to a substantial environmental contamination. This in turn accounts for a significant exposure of the general human population, with rather high exposure levels being attained in occupational settings. Investigations on the genotoxic activity of PCP have given rise to divergent results which would seem to make an evaluation difficult. By grouping them into 3 categories a somewhat clearer picture, allowing finally an (admittedly tentative) assessment, can be obtained. PCP does seem to be at most a weak inducer of DNA damage: it produces neither DNA-strand breaks nor clear differential toxicity to bacteria in rec-assays in the absence of metabolic activation. Also in SCE induction no increase can be observed in vivo, while PCP is found marginally active in a single in vitro experiment. Metabolic activation, however, leads to prophage induction and to DNA strand breaks in human lymphocytes, presumably through the formation of oxygen radicals. A possible further exception in this area might be the positive results in the yeast recombination tests, although their inadequate reporting makes a full evaluation difficult. PCP does not seem to induce gene (point) mutations, as most bacterial assays, the Drosophila sex-linked recessive lethal test and in vitro assays with mammalian cells did not demonstrate any effects. Marginally positive results were obtained in the mammalian spot test in vivo and in one bacterial test; the positive result in the yeast assay for cycloheximide resistance is fraught somewhat with its questionable genetic basis. PCP does, however, induce chromosomal aberrations in mammalian cells in vitro and in lymphocytes of exposed persons in vivo. Those in vivo results that were unable to provide evidence of chromosomal damage are hampered either by methodological inadequacies or by too low exposure levels. The (rodent) metabolite tetrachlorohydroquinone might be a real genotoxic agent, capable of binding to DNA and producing DNA strand breaks; this activity is probably due to semiquinone radical formation and partly mediated through active oxygen species. Since this compound has not been tested in the common bacterial and mammalian mutagenicity assays, the few ancillary results on this substance cannot be used in a meaningful human risk assessment of PCP. Furthermore, this metabolite has only been produced by human liver microsomes in vitro, but has not been detected in exposed humans in vivo. [Seiler JP; Mutat Res 257 (1) 27-47 (1991)]**PEER REVIEWED**
  
• Urinary PCP was monitored in male volunteers exposed to Fungifen solution which is a readily accessible pharmaceutical product containing 1% of PCP as active ingredient, and is recommended for the local treatment of interdigital mycoses. PCP absorbed readily through the skin and its elimination was slow. After the topical application of Fungifen, maximumlevels of urine PCP ranged from 109 to 1290 ug/l. In a single case a peak value of 3200 ug/l was measured. At the same time, PCP could be detected in the saliva, too. Urinary preexposure levels (ranged around 10 ug/l) were reached within 75 and 90 days, respectively. Maximum urinary levels represent exposures corresponding to occupational ones, known from other studies. The toxicity of PCP as well as the health risk of the Fungifen use to the great masses of the people (including pregnant women and children) are discussed. [G:onczi C et al; Orv Hetil 132 (7): 361-3 (1991)]**PEER REVIEWED**
  
• Immune parameters were examined in 188 patients who were exposed for more than 6 mo to pentachlorophenol containing pesticides. Blood levels of pentachlorophenol, lymphocyte populations, in vitro responses to mitogenic and allogenic stimulation, plasma neopterin levels, plasma cytokine and cytokine receptors were determined. Impaired in vitro lymphocyte stimulation responses were impaired in 65% of the patients. ... Impaired lymphocyte stimulation incr significantly with levels of pentachlorophenol that exceeded 10 ul/l (p<0.05). Patients who had high levels of pentachlorophenol and abnormal lymphocyte stimulation also had incr proportions of blood monocytes in blood (p<0.05), as well as incr IL-8 serum levels (p<0.02). Eleven patients had abnormal mitogen stimulation experienced decr CD4/CD8 ratios of < 1.0; 5 of these patients had decr CD4+ lymphocyte counts of <500/ul, and 3 patients had incr plasma neopterin of >15 nmol/l. ... This indicates that incr levels of pentachlorophenol in blood can lead to severe T lymphocyte dysfunction. [Daniel V et al; 50 (4): 287 (1995)]**PEER REVIEWED**
  
• Excessively treated interior surfaces may be a source of exposure sufficient to cause irritation of eyes, nose, and throat. [Morgan DP; Recognition and Management of Pesticide Poisonings. 4th ed. p.73 EPA 540/9-88-001. Washington, DC: U.S. Government Printing Office, March 1989]**PEER REVIEWED**
  

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Non-Human Toxicity Excerpts

• TOXICITY OF PENTACHLOROPHENOL TO SHEEP & CALVES HAS BEEN EXAMINED ... MIN ACUTE LETHAL DOSE RATE WAS FOUND TO BE APPROX 120 & 140 MG/KG RESPECTIVELY IN THE 2 SPECIES. ... DEATH OCCURRED IN 2 TO 14 HR. MOST PROMINENT CLINICAL SIGN WAS ACCELERATED BREATHING ... WHICH DISTINGUISHED DOSED ANIMALS FROM CONTROLS 1 TO 2 HR AFTER /ORAL/ DRENCHING. BADLY AFFECTED ANIMALS STOOD SWAYING, WITH HEAD LOWERED, PANTED NOISILY, & MADE LITTLE ATTEMPT TO MOVE WHEN APPROACHED. SALIVATION WAS OBSERVED IN CALVES & COAT FELT DAMP. RECOVERY FROM THIS STAGE ... WAS RAPID & COMPLETE. IN FATAL CASES, COMPLETE COLLAPSE OCCURRED, ANIMALS LYING WITH LEGS LIMP & PANTING VIGOROUSLY THROUGH OPEN MOUTH. ASPHYXIAL TREMORS, BUT NO CONVULSIONS, SET IN JUST BEFORE DEATH. [Clarke, M. L., D. G. Harvey and D. J. Humphreys. Veterinary Toxicology. 2nd ed. London: Bailliere Tindall, 1981., p. 132]**PEER REVIEWED**
  
• POST MORTEM, ACUTELY POISONED SHEEP /FROM ORAL DRENCHING/ SHOWED GENERALIZED CONGESTION. LYMPH NODES APPEARED ENLARGED & EDEMATOUS. THERE WERE HEMORRHAGES IN EPICARDIUM & ALONG AORTA. LUNG SHOWED ISOLATED AREAS OF COLLAPSE & GENERALIZED CONGESTION. BLOOD SPLASHES WERE OCCASIONALLY SEEN ON DIAPHRAGM. STOMACH, INTESTINES, LIVER & KIDNEY SOMETIMES SHOWED MILD CONGESTION. BLADDER INVARIABLY EMPTY. [Clarke, M. L., D. G. Harvey and D. J. Humphreys. Veterinary Toxicology. 2nd ed. London: Bailliere Tindall, 1981., p. 132]**PEER REVIEWED**
  
• PURIFIED & COMMERCIAL GRADES ... GIVEN ORALLY TO /SPRAGUE-DAWLEY/ RATS AT DOSES RANGING FROM 5-10 MG/KG BODY WT/DAY AT VARIOUS INTERVALS DURING DAYS 6-15 OF PREGNANCY. SIGNS OF EMBRYOTOXICITY & FETOTOXICITY ... RESORPTIONS, SC EDEMA, DILATED URETERS & ANOMALIES OF SKULL, RIBS, VERTEBRAE & STERNEBRAE WERE OBSERVED AT INCIDENCE WHICH INCR WITH DOSE. EARLY ORGANOGENESIS ... MOST SENSITIVE PERIOD. NO-EFFECT ... LEVEL OF COMMERCIAL GRADE WAS 5 MG/KG/BODY WT/DAY; PURIFIED PENTACHLOROPHENOL GIVEN AT SAME ... LEVEL CAUSED ... SIGNIFICANT INCR IN INCIDENCE OF DELAYED OSSIFICATION OF SKULL BONES BUT NO OTHER EFFECT ON ... DEVELOPMENT. INGESTION OF 3 MG/KG BODY WT/DAY OF COMMERICALLY AVAILABLE PURIFIED GRADE HAD NO EFFECT ON REPRODUCTION, NEONATAL GROWTH, SURVIVAL OR DEVELOPMENT. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V20 315 (1979)]**PEER REVIEWED**
  
• A single 60 mg/kg body wt oral dose of purified pentachlorophenol was given to pregnant Charles River CD strain rats on days 8, 9, 10, 11, 12, or 13 of gestation. Treatment on days 9 or 10 had the greatest effect on fetotoxicity. [National Research Council. Drinking Water and Health, Volume 6. Washington, D.C.: National Academy Press, 1986., p. 392]**PEER REVIEWED**
  
• SIX GROUPS OF 27 MALE & ... FEMALE WEANLING SPRAGUE-DAWLEY (SPARTAN SUBSTRAIN) RATS ... GIVEN LAB CHOW ... CONTAINING PENTACHLOROPHENOL (SAMPLE XD-9108.002: PENTACHLOROPHENOL 90.4%; TETRACHLOROPHENOL 10.4%; TRICHLOROPHENOL LESS THAN 0.1%; HEPTA- & OCTACHLORODIBENZO-P-DIOXINS ABOUT 21 MG/KG; HEXA- & HEPTACHLORODIBENZOFURANS ABOUT 5.2 MG/KG; & HEXACHLOROBENZENE 400 MG/KG) TO PROVIDE ... LEVELS OF 0, 1, 3, 10 OR 30 MG PCP/KG BODY/DAY. PENTACHLOROPHENOL WAS DISSOLVED IN ANISOLE & CONCN ... ADJUSTED ON A MONTHLY BASIS TO MAINTAIN DESIGNATED DOSE LEVELS ... GROUPS OF 27 MALE & 27 FEMALE CONTROLS ... RECEIVED LAB CHOW CONTAINING ANISOLE ONLY. FEMALE RATS WERE MAINTAINED ON TEST DIETS FOR 24 MO, BUT THE MALE/S/ ... WERE TAKEN OFF ... AFTER 22 MO BECAUSE OF HIGH MORTALITY ...THE TOTAL & INDIVIDUAL TUMOR INCIDENCES BY SITES, TIMES OF APPEARANCE ... & AVG NUMBERS ... PER ANIMAL (PREDOMINANTLY BENIGN NEOPLASMS) WERE NOT SIGNIFICANTLY DIFFERENT FROM THOSE OBSERVED IN CONTROL RATS. THE NUMBER OF RATS WITH TUMORS/THOSE EXAM WERE, IN MALES: 11/27 (CONTROLS), 13/26 (1 MG/KG), 13/27 (3 MG/KG), 12/27 (10 MG/KG), 11/27 (30 MG/KG); IN FEMALES: 27/27 (CONTROLS), 26/27 (1 MG/KG), 25/27 (AT ALL OTHER DOSES). [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V20 313 (1979)]**PEER REVIEWED**
  
• GROUPS OF 18 MALE & ... FEMALE (C57BL/6XC3H/ANF)F1 MICE & 18 MALE & FEMALE (C57BL/6XAKR)F1 MICE RECEIVED ... DOWCIDE-7 (IMPURITIES UNSPECIFIED) ... /AT/ 46.4 MG/KG BODY WT IN 0.5% GELATIN AT 7 DAYS OF AGE BY STOMACH TUBE & SAME AMT (NOT ADJUSTED FOR INCR BODY WT) DAILY UP TO 4 WK OF AGE; SUBSEQUENTLY, THE MICE WERE FED 130 MG/KG /PPM/ DIET UNTIL ... 78 WK OF AGE AT WHICH TIME 16, 18, 17 & 16 MICE WERE STILL ALIVE IN THE 4 GROUPS, RESPECTIVELY. TUMORS DEVELOPED IN 3/18, 4/18, 3/17 AND 2/18 MALE & FEMALE ... MICE; THESE INCIDENCES WERE NOT SIGNIFICANTLY GREATER THAN IN 79-90 NECROPSIED MICE OF EACH SEX & STRAIN, WHICH HAD EITHER BEEN UNTREATED OR HAD RECEIVED GELATIN ONLY. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V20 309 (1979)]**PEER REVIEWED**
  
• GROUPS OF 18 MALE & 18 FEMALE (C57BL/6XC3H/ANF)F1 MICE & 18 MALE & 18 FEMALE (C57BL/6XAKR)F1 MICE ... GIVEN SINGLE SC INJECTIONS OF 46.4 MG/KG BODY WT ... (DOWCIDE-7; IMPURITIES UNSPECIFIED) IN CORN OIL AT 28 DAYS OF AGE & WERE OBSERVED UP TO 78 WK OF AGE, AT WHICH TIME 14, 18, 18 & 16 MICE IN THE 4 GROUPS, RESPECTIVELY WERE STILL ALIVE. NEG CONTROL GROUPS CONSISTED OF ANIMALS THAT WERE EITHER UNTREATED OR RECEIVED GELATIN, CORN OIL OR DIMETHYLSULFOXIDE & COMPRISED 141 MALES & 154 FEMALES OF THE FIRST STRAIN AND 161 MALES & 157 FEMALES OF THE SECOND STRAIN. THE INCIDENCES OF HEPATOMAS (4/17) IN MALES OF 1ST STRAIN WAS SIGNIFICANTLY INCR ... OVER THAT IN CONTROLS (9/141). [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V20 313 (1979)]**PEER REVIEWED**
  
• Acute and chronic toxicity to saltwater aquatic life occur at concentrations as low as 53 and 34 ug/l, respectively. [USEPA; Ambient Water Quality Criteria Doc: Pentachlorophenol p.B-10 (1980) EPA 440/5-80-065]**PEER REVIEWED**
  
• Twenty one day chronic mortality of Daphnia magna was produced at 320 ug/l, but not at 180 ug/l. [USEPA; Ambient Water Quality Criteria Doc: Pentachlorophenol p.B-5 (1980) EPA 440/5-80-065]**PEER REVIEWED**
  
• IN FEEDING EXPT WITH DROSOPHILA MELANOGASTER, 7 MILLIMOLAR PENTACHLOROPHENOL FAILED TO INDUCE SEX-LINKED RECESSIVE LETHALS IN MEIOTIC & POSTMEIOTIC STAGES OF MALE GERM CELLS. IN LATERAL ROOTS OF VICIA FABA SEEDLINGS TREATED WITH 43.5-174 MG/L ... THERE WAS INCR IN FREQUENCY OF ABNORMAL CELL DIVISIONS (EG, STICKINESS & LAGGING OF CHROMOSOMES & CHROMOSOME FRAGMENTATION); THESE ABNORMALITIES WERE MORE FREQUENT DURING METAPHASE THAN IN EARLIER STAGES &, IN GENERAL, INCR WITH INCR CONCN. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V20 316 (1979)]**PEER REVIEWED**
  
• The no observable effect level for fetal resorption in pregnant Sprague Dawley female rats was 5.8 mg/kg/day of commercial grade pentachlorophenol and 15 mg/kg/day of purified pentachlorophenol. Measurements were also taken on fetal body weight and crown rump length, both of which decreased with increasing dose. The no observable effect level for these parameters was 15 mg/kg/day for both commercial grade and purified pentachlorophenol. [USEPA; Wood Preservative Position Doc 2/3: p.248 (1981)]**PEER REVIEWED**
  
• Pregnant Syrian golden hamsters given daily oral doses of pentachlorophenol (unspecified purity) ranging from 1.25 to 20 mg/kg from days 5 to 10 of gestation experienced an increase in fetal deaths & resorptions. The no effect level was 2.5 mg/kg/day. [National Research Council. Drinking Water and Health, Volume 6. Washington, D.C.: National Academy Press, 1986., p. 392]**PEER REVIEWED**
  
• Pentachlorophenol: ... (0, 5, 50, or 500 ppm) /was administered/ to Sprague-Dawley rats in the diet beginning with the rats own weaning through the weaning of their pups. ... Significant effects /were observed/ on the immune system (as indicated by decreased antibody titers, decreased delayed hypersensitivity to oxazolone, and increased peritoneal macrophage numbers) & reduced ethylnitrosourea-induced transplacental carcinogenesis. [National Research Council. Drinking Water and Health, Volume 6. Washington, D.C.: National Academy Press, 1986., p. 392]**PEER REVIEWED**
  
• ... Effects /were/ observed ... on the central nervous system in rabbits after 60 days of exposure to subcutaneous doses of 5%, 10% & 25% of the minimum lethal dose (275 mg/kg body wt). Nervous system lesions were seen in all dose groups. Neurochemical effects were observed in 30 male Wistar rats given 20 mg/l concn of technical grade pentachlorophenol in drinking water for 3 to 14 wk. Thirty controls were also studied. ... The main effects seen in the rat brain were transient biochemical effects ... . [National Research Council. Drinking Water and Health, Volume 6. Washington, D.C.: National Academy Press, 1986., p. 391]**PEER REVIEWED**
  
• In a 160 day study, cattle fed 20 mg/kg doses of technical pentachlorophenol for 42 days, followed by 15 mg/kg/day for the remainder of the study, had decreased wt gain, progressive anemia, & immune effects. Only minimal adverse effects were observed after exposure to analytical grade pentachlorophenol. [National Research Council. Drinking Water and Health, Volume 6. Washington, D.C.: National Academy Press, 1986., p. 390]**PEER REVIEWED**
  
• PENTACHLOROPHENOL WAS EMBRYOTOXIC & FETOTOXIC /TO SPRAGUE-DAWLEY RATS/ @ DOSES OF COMMERCIAL & PURE PENTACHLOROPHENOL OF 15 MG/KG & ABOVE. ... DELAYED OSSIFICATION OF SKULL WAS OBSERVED AFTER TREATMENT WITH PURE PENTACHLOROPHENOL. ORAL ADMIN ... TO HAMSTERS ON DAYS 5-10 OF GESTATION PRODUCED FETAL DEATH &/OR RESORPTIONS AT 5 MG/KG/DAY AND ABOVE. [National Research Council. Drinking Water & Health Volume 1. Washington, DC: National Academy Press, 1977., p. 753]**PEER REVIEWED**
  
• PROVED NEGATIVE IN SEX-LINKED LEVEL TEST IN DROSOPHILA ... . [National Research Council. Drinking Water & Health Volume 1. Washington, DC: National Academy Press, 1977., p. 753]**PEER REVIEWED**
  
• The effects of pure and technical grade pentachlorophenol on primary cultured rat hepatocytes were compared to determine if contaminants of commercial preparations of pentachlorophenol increased its toxicity. Hepatocytes isolated from adult Sprague-Dawley rats were incubated with analytical /grade/ pentachlorophenol of 99% purity, technical grade pentachlorophenol, or its sodium salt, which contains only minor concentrations of technical impurities. Monooxygenase activity was markedly induced by technical grade pentachlorophenol in a concentration dependent pattern, with a maximum response of approximately 14 fold seen at concentrations of 30 to 50 micromoles. Monooxygenase induction was much less marked after exposure to 50 micromoles sodium salt of technical pentachlorophenol, only 2.7 fold, and was barely detectable after exposure to 50 micromoles 99% purity pentachlorophenol. Phase II metabolism of monooxygenase product was equally inhibited by pretreatment with any of the pentachlorophenol preparations. Cell membrane damage, assessed by leakage of LDH into the culture medium, was also observed with all the pentachlorophenol preparations tested. These results indicated that monooxygenase induction was attributable to technical impurities, while cytotoxic effects were caused by the pentachlorophenol itself. [Wollesen C et al; Chemosphere 15 (9-12): 2125-8 (1986)]**PEER REVIEWED**
  
• The teratogenic activities of highly purified pentachlorophenol and pentachloroanisole, administered in the diet of Sprague Dawley rats of both sexes, at the rate of 4, 13 or 43 mg/kg and 4, 12 or 41 mg/kg/day, respectively, for a period of 181 days, were investigated. Pregnant females treated with pentachlorophenol ate more food than untreated controls. As compared to controls, dams treated with the highest doses of both compounds had a lower body wt on day 0 of gestation and gained less weight during their pregnancy. Animals treated with the highest dose of pentachlorophenol gained less weight during pregnancy than controls. Embryonic deaths were recorded following treatment with pentachlorophenol at the rate of 43 mg/kg/day, while lower doses of the compound induced dose related reductions in body wt. At the rate of 13 mg/kg/day only, pentachlorophenol reduced the crown to rump length and increased the skeletal alterations of the fetus. Decreased numbers of corpora lutea and embryonic death were recorded following the administration of pentachlorophenol at the rate of 4 and 41 mg/kg/day. At the same dose pentachlorophenol reduced the body wt and the crown to rump length of male fetuses, while their female counterparts were not affected. Neither pentachlorophenol nor pentachloroanisole affected the soft tissue of the animals. Results indicate the pentachlorophenol is slightly more toxic than pentachloroanisole in Sprague Dawley rats. [Welsh JJ et al; Food Chem Tox 25 (2): 163-72 (1987)]**PEER REVIEWED**
  
• In a 7 day experiment, food conversion efficiency (as g of growth/g of food eaten) in fry of largemouth bass was significantly affected in a concentration-dependent fashion at concentration of pentachlorophenol >10 ug/l; with exposure to increasing pentachlorophenol concn >10 ug/l, there was a significant concentration-related reduction in total length of largemouth bass at the end of a 57 day exposure. For the length data, the threshold response value was 25.2 ug/l which was very close to that of the food-coversion efficiency value (23.4 ug/l). When comparing pentachlorophenol induced mortality, behavioral responses, length at the end of a long-term exposure, and food-conversion efficiency, the latter two are the most sensitive indicators of pentachlorophenol effects on fish. [Johansen PH et al; Bull Environ Contam Toxicol 39 (3): 379-84 (1987)]**PEER REVIEWED**
  
• Rainbow trout were exposed for 4 or 8 days to various types of toxicants, each applied to the test water at a high sublethal concn. The activity of liver UDP-glucuronosyltransferase was assayed from the submitochondrial fraction using p-nitrophenol as an aglycone. Activity of UDP-glucuronosyltransferase was inhibited ... by pentachlorophenol, a toxicant regularly found in effluents of the pulp and paper industry. [Castren M, Oikari A; Comp Biochem Physiol C Comp Pharmacol Toxicol 86C (2): 357-60 (1987)]**PEER REVIEWED**
  
• The induction of mutation of the hypoxanthine-guanine phosphoribosyl transferase locus and cytotoxicities of 6 different chlorophenols (2,4- and 2,6-dichlorophenol, 2,4,5- and 2,4,6-trichlorophenol, 2,3,4,6-tetrachlorophenol and pentachlorophenol) were examined in V79 Chinese hamster cells without exogenous metabolic activation. The chlorophenols were cytotoxic to V79 cells, but fail to produce significant increases in the frequency of 6-thioguanine-resistant mutants. [Jansson K, Jansson V; Mutat Res 171 (2-3): 165-8 (1986)]**PEER REVIEWED**
  
• Largemounth bass Micropterus salmoides were reared over their first 8 weeks of free-swimming life in uncontaminated control water or in water containing one of five concentrations of pentachlorophenol ranging from 1.6 to 88 ug/l. Over the final 3 weeks of the study, fish reared in concentrations of 67 and 88 ug pentachlorophenol/l performed significantly fewer feeding acts (orientations, bites) and had a lower rate of prey capture than did control fish. However, fish in high concentrations spent significantly more time swimming than did control fish, which indicated that exposure to pentachlorophenol made them hyperactive. By inhibiting energy intake while inducing higher energy expenditures, pentachlorophenol may reduce survival of young largemouth bass over the winter. [Brown JA et al; Trans Am Fish Soc 116 (1): 71-8 (1987)]**PEER REVIEWED**
  
• The immunosuppressive effects produced by exposure to technical grade pentachlorophenol were compared with those produced by purified pentachlorophenol both in vitro and in vivo in mice. Female B6C3F1 mice were administered daily doses of 10, 30, or 100 mg/kg technical grade pentachlorophenol, or corn oil via gastric intubation for 14 days. Animals were sacrificed the day after the last dose, and antibody responses to multiple antigenic stimuli were measured in spleen cell suspensions from the mice. There were no differences in the antibody responses in the spleen cell suspensions from technical grade pentachlorophenol or purified pentachlorophenol treated animals as compared to controls. When mice were immunized with sheep erythrocytes on day 10 or 11 of the 14 day exposure period, there was a dose dependent suppression of the immunoglobulin-M antibody response to sheep erythrocytes in spleen cells from mice treated with technical grade pentachlorophenol. No changes were observed in the antibody responses of spleen cells from mice to purified pentachlorophenol which were immunized during exposure. When added directly to spleen cell cultures from untreated mice, both technical grade pentachlorophenoland purified pentachlorophenol suppressed the in vitro antibody responses and were cytotoxic to the spleen cells. The in vitro antibody assay is of limited value in studying the mechanism of immunosuppression by technical grade pentachlorophenol, and that technical grade pentachlorophenol induced immunosuppression cannot be attributed to a direct effect on immunocompetent cells. [Holsapple MP et al; J Tox Environ Health 20 (3): 229-39 (1987)]**PEER REVIEWED**
  
• The effects of chronic dietary exposure to technical grade pentachlorophenol on humoral immune responses in mice were examined. Primary and secondary splenic antibody responses to the T-dependent antigen, sheep red blood cells, were examined in mice using the Hemolytic Antibody Isotope Release assay. To assess the direct effects of technical grade pentachlorophenol on B cells, the splenic plaque-forming cell response and serum antibody titers to the T-independent antigen, dinitrophenyl Ficoll, were examined. Technical grade pentachlorophenol exposure altered the kinetics and the magnitude of the humoral antibody responses to sheep red blood cells and dinitrophenyl Ficoll. Peak splenic antibody production and serum antibody responses were dose-dependently suppressed by technical grade pentachlorophenol exposure. IgM responses appeared to be more sensitive to technical grade pentachlorophenol induced suppression than the IgG response. Significant depresssion of the IgM anti-sheep red blood cells splenic hemolytic antibody isotope release response was apparent as early as 2 wk after initiation of technical grade pentachlorophenol exposure and persisted for at least 8 wk after terminination of technical grade pentachlorophenol feeding. Liver weight and serum lactate dehydrogenase and alanine aminotransferase levels were significantly elevated during technical grade pentachlorophenol exposure and returned to control levels after a 4-6 wk recovery period. The immunotoxic effect of pentachlorphenol on humoral immunity was observed only in animals exposed to technical grade pentachlorphenol known to be contaminated with significant levels of other chlorinated phenols as well as nonphenolic impurities including chlorinated dioxins, furans, and diphenyl ethers. Animals exposed to analytical grade pentachlorophenol did not exhibit depressed humoral immunity. [Kerkvliet NI et al; Fundam Appl Toxicol 2 (2): 90-9 (1982)]**PEER REVIEWED**
  
• The rat embryo was shown to be most susceptible to the toxic effect of pentachlorophenol during the early phases of organogenesis. [American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 1177]**PEER REVIEWED**
  
• Mean oral: LD50 for female mallards at age 3 mo was 380 mg/kg and for female pheasants at age 3-6 mo, 504 mg/kg./ Signs of intoxication: Polydipsia and regurgitation (in mallards), tachypnea, wing shivers or twitching, jerkiness, shakiness, ataxia, imbalance, tremors, and spasms. Signs appeared as soon as 10 min and mortalities in mallards usually occurred between 2 and 24 hr after treatment and in pheasants between 3 and 5 days after treatment. However, one pheasant died after about 3 hr and one died between 10 and 12 days after treatment. Remission took up to 2 wk. [U.S. Department of the Interior, Fish and Wildlife Service. Handbook of Toxicity of Pesticides to Wildlife. Resource Publication 153. Washington, DC: U.S. Government Printing Office, 1984., p. 63]**PEER REVIEWED**
  
• By means of controlled laboratory experiments it was established that timber treatment fluids containing gamma hexachlorocyclohexane and pentachlorophenol and used according to manufacturers' recommendations rapidly cause the death of pipistrelle bats roosting in contact with timber treated between six weeks and 14 months previously. The chemicals responsible are presumably ingested when the bats groom their fur after they have been in contact with the treated timber. Bats prevented from establishing such bodily contact took longer to die indicating that absorption of the vapor phase of the tested chemicals also takes place across the skin or respiratory epithelium. Acrylic resin reduces the lethal effect when used as a sealant over wood treated with gamma-hexachlorocyclohexane and pentachlorophenol, but polyurethane varnish does not. It has also been established that no obvious harm is caused to bats roosting for 16 to 22 weeks in contact with timber treated with the synthetic pyrethroids permethrin, cypermethrin and deltamethrin at concentrations which have previously proved effective for the control of wood boring beetles. Similarly, no obvious harm is caused to bats roosting for 13 weeks in contact with timber treated with the fungicides borester 7 and zinc octoate. However, greater mortality was recorded in bats housed in cages treated with the fungicide tributyltin oxide than in control groups. It is clear from these results that synthetic pyrethroids should replace gamma-hexachlorocylcohexane for the treatment of wood boring beetles in bat roosts. A high priority should be accorded to replacing pentachlorophenol with a fungicide which is not toxic to bats. [Racey PA, Swift SM; Biol Conserv 35 (3): 205-14 (1986)]**PEER REVIEWED**
  
• The suitability of ejaculated bovine spermatozoa as an in vitro model of the assessment of the cytotoxic potential of chemicals was evaluated using several endpoints: swimming activity, adenine nucleotide content, membrane integrity and oxygen consumption. A series of chlorophenols inhibited sperm motion (motility and velocity) in a concentration dependent manner. This could be determined quantitatively and reproducibly by means of videomicrography and automatic computer image analysis. The sper immobilizing potency increased with increasing chlorination and was positively correlated with lipophilicity. Concentrations which reduced the percentage of moving sperm to 50% of controls ranged from 43 muM for pentachlorophenol to 1440 muM for 4-monochlorophenol. Determinations of adenine nucleotides and percentages of viable cells revealed qualitative differences between the action of pentachlorophenol and the lower chlorinated phenols. While the latter decreased the total adenine nucleotide contents and the percentage of unstained cells in parallel to motion inhibition, no such changes occurred after exposure to immobilizing concentrations of pentachlorophenol. Penta-, tetra-, and trichlorinated phenols stimulated cellular respiration, indicating their uncouping activity, at concentrations lower than those necessary for motion inhibition. The results indicate that bovine spermatozoa may become a useful in vitro model for the toxicological evaluation of chemicals providing quantitative as well as qualitative data. [Seibert H et al; Cell Biol Toxicol 5 (3): 315-30 (1989)]**PEER REVIEWED**
  
• The acute toxicity of a technical formulation of pentachlorophenol and pure pentachlorophenol to three age classes of Daphnia magna, and adult Daphnia pulex and Daphnia galeata mendotae was determined by static toxicity tests. The influence of a number of factors on toxicity of pentachlorophenol was also examined. The 48 hr LC50 estimates for adult daphnids of the three species exposed to pure pentachlorophenol were 1.78, 4.59 and 0.51 mg/l, respectively, while those for the technical formulation were 2.57, 3.66 and 0.33 mg/l, respectively. There was little difference in toxicity between the technical and pure pentachlorophenol; however, toxicity of both forms of pentachlorophenol was influenced by duration of exposure, age (and/or size) and species of test organism and pH of the test solution. Pentachlorophenol caused a toxic response over a very narrow range of concentrations, with the greatest response occurring immediately between 0 and 24 hr. Pure pentachlorophenol was equally toxic to all age classes of Daphnia magna but susceptibility to technical pentachlorophenol decreased with maturation. Daphnia galeata mendotae was ten times more sensitive than Daphnia pulex to pentachlorophenol. Pure pentachlorophenol was significantly more toxic to Daphnia magna at pH 5.5 than 7.0 with mean 48 hr LC50 values of 0.082 and 1.78 mg pentachlorophenol/l, respectively. At 12 deg C, the toxicity of both forms of pentachlorophenol to Daphnia galeata mendoate and Daphnia pulex did not differ significantly from that at 20 deg C; however, technical pentachlorophenol was significantly more toxic to Daphnia magna at 12 deg C for an exposure duration of 48 hr. There was no effect of test container size (100, 250, 600 and 1,000 ml) on the toxicity of pentachlorophenol to Daphnia magna at 20 deg C with the lower pH of 5.5, suggesting that adsorption to glassware was not a factor in availability of pentachlorophenol to test organisms. Beaker size had no effect on the toxicity of pentachlorophenol to Daphnia pulex at 20 deg C with test solutions having a pH of 7.0-8.0. [Stephenson GL et al; Arch Environ Contam Toxicol 20 (1): 73-80 (1991)]**PEER REVIEWED**
  
• In this investigation the effects of chlorophenols on rat liver mitochondrial respiratory parameters were determined and compared to the toxicities of those compounds in a variety of biological systems currently being used for toxicity testing. Mitochondrial fractions were exposed to six concentrations of five different chlorophenols in a semiclosed, 2 ml reaction vessel. Respiratory parameters were measured polarographically with an oxygen electrode and compared to control experiments. The toxicity of the chlorophenols, as measured by the concentration reducing the respiratory control ratio of the control to 50%, increased with increasing chloro substitution. The concentrations reducing the respiratory control ratio of the control to 50% ranged from 599 muM with 2 chlorophenol to 0.110 muM with pentachlorophenol. The RCR50 concentrations for the five chlorophenols were compared to six physicochemical parameters for the same chlorophenols; high degrees of correlation between the the concentrations reducing the respiratory control ratio of the control to 50% and the physicochemical parameters were found (r : 0.890). The highest correlation coefficient obtained was with the n-octanol/water partition coefficient (r = 0.991), indicating that the ability of chlorophenols to partition into the lipid mitochondrial membrane plays a significant role in eliciting its toxic effects. The concentrations reducing the respiratory control ratio of the control to 50% were also compared to nine currently existing short-term toxicity tests. High degrees of correlation were obtained with several of the tests, including algal, bacterial, and fish bioassays. This suggests that the uncoupling of oxidative phosphorylation may be the major mechanism by which chlorophenols cause toxicity to intact cells as well as more complex organisms. The use of mitochondrial respiratory parameters appears to offer a complementary approach as a short term toxicity test for this class of compounds. Further development and testing with a variety of other toxicants is suggested. [Shannon RD et al; Environ Toxicol Chem 10 (1): 57-66 (1991)]**PEER REVIEWED**
  
• GF-Scale cells, a fibroblastic cell line derived from the scale of golfish, were used for the determination of the cytotoxicity of chlorophenols and the quantitative structure-activity relationship studies. As the cytotoxicity end point, the amount of neutral red retained by viable cells after exposure to chemicals was quantified. The sequence of cytotoxicity based on the concentration of chemicals that reduced uptake of neutral red by 50% was penta-chloro > 2,4,5-trichloro > 2,3,4-trichloro > 2,3,4,6-tetrachloro > 3,5-dichloro > 3,4-dichloro > 2,4-dichloro > 2,5-dichloro > 2,3-dichloro > 2,4,6-trichloro > 3-chloro > 4-chloro > 2,6-chloro > phenol. The in vitro cytotoxicity of these chemicals was found to be significantly correlated to their in vivo acute toxicity to aquatic species, and the concentrations of chemicals that reduced uptake of neutral red by 50% were correlated with six physiochemical parameters of chlorophenols. N-Octanol/water partition coefficient gave the best correlation in simple linear regression analysis, as is frequently stated in toxicity studies with aquatic animals. Multiparametric linear regression equations yielded improved correlation coefficients and predictive capabilities, including the n-octanal/water partition coefficient and pKa. These results suggest that in vitro fish cytotoxicity assays using the GF-Scale cell line are useful for ecotoxicity screening of aquatic pollutants. [Saito H et al; Environ Toxicol Chem 10 (2): 235-42 (1991)]**PEER REVIEWED**
  
• Effects of administration of equimolar doses of hexachlorobenzene and its metabolites pentachlorophenol and tetrachlorohydroquinone on serum thyroxine and triiodothyronine levels in rats were studied. Furthermore, it was investigated whether the observed effects were related to the serum levels of hexachlorobenzene or pentachlorophenol. Rats received either corn oil (controls) or hexachlorobenzene, pentachlorophenol or tetrachlorohydroquinone in a single equimolar intraperitoneal dose of 0.056 mmol/kg. Results indicated that hexachlorobenzene did not alter serum thyroxine and triiodothyronine levels for a period up to 96 hr after dosing. In contrast, pentachlorophenol and tetrachlorohydroquinone were both capable of reducing serum thyroxine levels with a maximum effect between 6 and 24 hr after exposure. Tetrachlorohydroquinone was more effective in repressing triiodothyronine than thyroxine blood levels. Dose response experiments were carried out in order to obtain insight into the sensitivity of the observed effects. Rats received different doses of pentachlorophenol or tetrachlorohydroquinone intraperitoneally. The reductions of thyroxine levels by pentachlorophenol were inversely related to serum pentachlorophenol levels in exposed animals, based on the toxicokinetics and dose response profiles. Furthermore, pentachlorophenol serum levels after hexachlorobenzene administration appeared too low to cause an effect. The results of this study indicate that not hexachlorobenzene itself, but rather its metabolites pentachlorophenol and tetrachlorohydroquinone may be involved in reduced serum thyroid hormone levels after hexachlorobenzene administration. [Van Raaij J A GM et al; Toxicology 67 (1): 107-16 (1991)]**PEER REVIEWED**
  
• Bluegill sunfish (Lepomis macrochirus), exposed to a 22 day subchronic exposure of pentachlorophenol at concentrations of approximately 20 and 75% of the 96 hr LC50, showed significant reductions in food conversion efficiency measured during the last 10 days of exposure. Bluegills exposed to a 3 day acute spill mimicking exposure of pentachlorophenol at a concentration of approximately 100% of the 96 hr LC50 failed to show a significant reduction in food conversion efficiency measured during the 10 days following exposure. Bluegill sunfish exposed to pentachlorophenol at continuous low level concentrations are at a greater risk for decreased growth than those exposed to a more concentrated short term pulse of toxicant. [Samis A JW et al; Aquat Toxicol (Amst) 19 (3): 231-40 (1991)]**PEER REVIEWED**
  
• To evaluate the toxicities of 37 xenobiotics detected in drinking water, primary cultures of rat hepatocytes were treated with the xenobiotics at a concentration of 0.5 mM. The toxicities were assessed by four cellular markers: leakage of intracellular lactate dehydrogenase activity, glycogenolytic activity as a specific function of hepatocytes, intracellular glutathione content, and observations of cytopathic effects. The cytotoxic assay revealed that pesticides of xenobiotics used in the current study were the most toxic at muM levels, that phenolic compounds had potent toxicity for the cultured cells while benzoic compounds did not, and that 3 carbon compounds with substitution of hydrogen to bromine or chlorine at both positions 1 and 3 were highly toxic. The order of hepatotoxicity on the basis of IC50 was, 1,3-dichloro-2-propanone > pentachlorophenol : 1,2-dibromo-3-chloro-propane > hepatachlor > 2,4,6-trichlorophenol : 2,4,6-tribromophenol. Since lag times were observed for the expression of cytotoxicity by the pesticides, biotransformation appeared important for the toxicity. Currently the concentration of pesticides is very low in the environment, and therefore the possibility of causing an impact on human health is low. However, the long lifetime and high lipophilicity of pesticides give them the potential to become some of the greatest environmental toxicants. [Murayama J-I et al; Eisei Kagaku 36 (4): 267-76 (1990)]**PEER REVIEWED**
  
• The inhibition of methane production by Methanosaeta concilii GP6, Methanospirillum hungatei GP1, Methanobacterium espanolae GP9, and Methanobacterium bryantii during short term (6 hr) exposure to eight benzene ring compounds was studied. The concentration that caused 50% inhibition of the methane production rate was dependent on the species and the toxicant. Pentachlorophenol was the most toxic of the tested compounds, with an IC50 of less than 8 mg/liter for all species except Methanospirillum hungatei. Abietic acid was the next most toxic compound for all the species, with an IC50 in the range of 1,225 to 32,400 mg/liter. 3-Chlorobenzoate was substantially more toxic (IC50, 450 to 1,460 mg/liter) than benzoate. The inhibition by benzene, phenol, vanillic acid, and toluene was intermediate to that of pentachlorophenol and benzoate. Long term incubation (days) studies to determine effect on growth indicated that all eight compounds were usually much more toxic than predicted from the short term data. In these latter studies, there was generally a good correlation in the observed inhibition as determined from growth and methane production. [Patel GB et al; Appl Environ Microbiol 57 (10): 2969-74 (1991)]**PEER REVIEWED**
  
• The toxicity of polychlorinated aromatic compounds was studied. Polychlorinated aromatic compounds in corn oil were administered to adult male and female albino mice, NMRJ strain, orally or by intraperitoneal injection. The median lethal dose for pentachlorophenol was 3.85 mg/mouse by the oral route and 1.75 mg/mouse by ip injection, for pentachloroanisole the values were 9.50 and 8.40, for tetrachlorocatechol 9.50 and 4.80, for tetrachlorohydroquinone 11.0 and 0.85, and for tetrachlororesorcinol the median lethal doses were 22.0 and 10.5 mg/mouse, respectively. After oral administration, pentachlorophenol was found to be the most toxic compound. After intraperitoneal administration, tetrachlorohydroquinone was found to be the most toxic compound. The animals that received 12 mg oral or ip single doses of tetrachlorodimethoxybenzenes did not die. Oral or ip single doses of tetrachlorobenzenediol-diacetates also produced no death. The groups of males dosed orally with tetrachlorohydroquinone, those dosed with tetrachlororesorcinol-diacetate, and the groups of males and females dosed intraperitoneally with tetrachlororesorcinol-diacetate showed a slower growth in body weight than controls. Microscopic examination of spleen, kidney, liver and lung tissue indicated unspecific bronchitis and inflammatory reaction in the hilar fat tissue in liver and slight infiltrates of lymphoid cells in some animals. [Renner G et al; Toxicological and Environmental Chemistry 11 (1): 37-50 (1986)]**PEER REVIEWED**
  
• The effects of pure and technical grade pentachlorophenol on primary cultured rat hepatocytes were compared to determine if contaminants of commercial preparations of pentachlorophenol increased its toxicity. Hepatocytes isolated from adult Sprague Dawley rats were incubated with analytical pentachlorophenol of 99 percent purity, technical grade pentachlorophenol, or its sodium salt (technical grade pentachlorophenol sodium salt), which contains only minor concentrations of technical impurities. Monooxygenase activity was markedly induced by technical grade pentachlorophenol in a concentration dependent pattern, with a maximum response of approximately 14 fold seen at concentrations of 30 to 50 micromoles. Monooxygenase induction was much less marked after exposure to 50 micromoles technical grade pentachlorophenol sodium salt, only 2.7 fold, and was barely detectable after exposure to 50 micromoles analytical pentachlorophenol. Phase II metabolism of monooxygenase product was equally inhibited by pretreatment with any of the pentachlorophenol preparations. Cell membrane damage, assessed by leakage of lactate dehydrogenase into the culture medium, was also observed with all the pentachlorophenol preparations tested. These results indicated that monooxygenase induction was attributable to technical impurities, while cytotoxic effects were caused by the pentachlorophenol itself. The authors conclude that the measurement of monooxygenase activity in cultured rat hepatocytes may provide a method of detecting enzyme inducers as contaminants in complex industrial chemicals. [Wollesen C et al; Chemosphere 15 (9-12): 2125-8 (1986)]**PEER REVIEWED**
  
• A study was designed to define the activity ranges of different chlorinated phenols in the series from monochlorophenol to pentachlorophenol in bacteria; to define the effect of these compounds on growth and viability parameters, correlating experimental findings with those obtained by enzymatic activities; and to define the relationships between toxicity and some physicochemical properties of these compounds. Escherichia coli was grown in the presence of test agents and assayed for growth and dehydrogenase and beta-galactosidase activities. Under these experimental conditions, the lag time to initiation of acclimation of growing cultures to phenol was 3 hours, while for chlorinated compounds it was about 2 hours longer. No effect of chlorine substituent number or concentration was seen. Toxicities of phenol, monochlorophenols, and polychlorophenols were differentiated by plotting specific growth rates, normalized to controls, against different concentrations. The validity of dehydrogenase activity in determining the toxicity of various phenol compounds by discriminating among different compounds was also demonstrated. Specific growth rate and dehydrogenase activity gave the best responses for quantitating toxicity and were compared for each phenol compound. The relative toxicity values showed that for both parameters the values obtained were lower than 10 for monochlorophenols and higher than 25 for polychlorinated phenols. A dependence of toxicity on phenol ionization constants was also noted. The authors conclude that use of specific growth rates and dehydrogenase activity in Escherichia coli is valid for evaluation of chemical toxicities of halogenated phenol compounds. [Cenci G et al; Bull Environ Contam Toxicol 38 (5): 868-75 (1987)]**PEER REVIEWED**
  
• The acute oral median lethal dose of technical grade pentachlorophenol was investigated in developing Sprague Dawley rats from 10 to 134 days old. Signs of acute toxicity included ataxia developing about 15 minutes after dosing, followed by rapidly developing motor weakness, hyperpyrexia, and rapid breathing about 25 minutes after dosing. Most deaths occurred either between 20 minutes and 2 hours, or between 4 hours and 8 hours following dosing. Those animals who recovered had little salivation, rectal temperatures only 1 to 3 degrees F above normal, and began to recover after 8 hours. Rats who were 10 to 20 days of age and not yet weaned and adult rats aged 70 to 134 days old formed the two most susceptible groups, far more susceptible than were juveniles aged 25 to 50 days, to the toxic effects of pentachlorophenol. The LD50 increased 4.4 times from postnatal day ten to postnatal day 25, plateaued from day 25 to 50, and decreased 2.8 times from day 50 to 134. The physiological reasons for the developmental susceptibility as evidenced in this study were not known. The authors suggest that functional changes in both the kidney and liver may be contributing factors. [St. Omer VEV, Gadusek F; Environ Toxicol Chem 6 (2): 147-9 (1987)]**PEER REVIEWED**
  
• The effect of pentachlorophenol on microsomal mixed function oxidases was studied in cattle. Four adult lactating Holstein cattle were fed 0.2 mg/kg technical grade pentachlorophenol for 75 to 84 days, followed by 2 mg/kg for 56 to 60 days. Twelve adult nonlaboratory Holstein cattle were administered 0, 0.1, 1.0, or 10.0 mg/kg purified pentachlorophenol for 95 days. The pentachlorophenol was administered directly into the rumen by way of a permanent cannula. Fifteen male calves were administered 1, 2, 10, or 20 mg/kg technical grade or purified pentachlorophenol from 5 to 43 days of age. The animals were observed for clinical signs of toxicity; they were killed at the end of the dosing period and the liver and lungs were removed and weighed. Liver and lung microsomes were prepared and assayed for benzo(a)pyrene-hydroxylase, ethoxycoumarin-O-deethylase, hexobarbital-hydroxylase, ethylmorphine-N-demethylase, aminopyrine-N-demethylase, cytochrome-P450(448), or cytochrome-b5. None of the adult cattle exhibited clinical signs of toxicity. Liver and lung weights were significantly elevated in cattle given technical grade pentachlorophenol. Liver and lung benzo(a)pyrene-hydroxylase was significantly increased in these animals. Purified pentachlorophenol had no effect on any enzyme activities. Toxic effects such as growth impairment and mortality were observed in calves fed 10 and 20 mg/kg pentachlorophenol. Liver weights were significantly increased. No toxic effects were seen in calves fed pure pentachlorophenol. Cytochrome-P450(448) and cytochrome-b5 were significantly increased by 10 mg/kg technical or pure pentachlorophenol. Technical grade pentachlorophenol at 1 and 10 mg/kg induced benzo(a)pyrene-hydroxylase and ethoxycoumarin-O-deethylase. The 10 mg/kg dose of purified pentachlorophenol also stimulated these enzymes. The /results suggest/ that pentachlorophenol induces organ enlargement and stimulates cytochrome-P450(448) and certain mixed function oxidases. Benzo(a)pyrene-hydroxylase is the most inducible enzyme. The effects observed with technical grade pentachlorophenol are attributed to chlorinated dioxin and furan impurities. Newborn cattle are more susceptible to the inducing properties of pentachlorophenol and its impurities than adults. [Shull LR et al; Pest Biochem Physiol 25 (1): 31-9 (1986)]**PEER REVIEWED**
  
• The effects of phenol and pentachlorophenol on axonal conduction and ganglionic transmission were studied in vitro. Desheathed sciatic nerves from toads (Caudiverbera caudiverbera) were incubated with up to 10 mM phenol, pentachlorophenol, or procaine (as a reference compound) for 20 minutes. The extent of axonal conduction block was determined by measuring the compound action potentials evoked by supramaximal stimulation. Desheathed sciatic nerve preparations were incubated with 0.3 to 3 mM pentachlorophenol for 20 minutes, following which the preparations were placed in fresh medium. Compound action potentials were measured for up to 60 minutes to assess the reversibility of the block. Sheathed or desheathed nerve preparations were incubated with 3 mM pentachlorophenol at pHs 7.0 and 9.0 to assess the effect of pH on the axonal block. Phenol, pentachlorophenol, and procaine induced axonal conduction block in a dose dependent manner. The doses for causing a 50% block were phenol 6.30 mM, pentachlorophenol 1.00 mM, and procaine 2.00 mM. The block was irreversible. Shifting the pH of the medium from 7.0 to 9.0 in the absence of pentachlorophenol caused a nonsignificant axonal conduction block. When pentachlorophenol was present the same pH change caused a significant decrease in the axonal block. The eighth ganglia from the paravertebral chain of C-caudiverbera spinal cords were incubated with 0.003 to 0.03 mM pentachlorophenol at pH 7.0 and 9.0. In some experiments 0.1 mM 3,4-diaminopyridine was present. The effects on synaptic transmission were assessed by measuring compound action potentials as before. Pentachlorophenol induced a synaptic transmission block that was dose dependent and irreversible. The pentachlorophenol induced block at pH 9.0 was significantly less than at pH 7.0. 3,4-Diaminopyridine antagonized the effect of pentachlorophenol. The authors conclude that pentachlorophenol, procaine, and phenol are able to block axonal conduction in toad nerve fibers, with PCP showing a much greater potency than procaine or phenol. [Montoya GA et al; Compar Biochem Physiol 89C: 377-82 (1988)]**PEER REVIEWED**
  
• The effects of chlorophenols on the function and viability of rat hepatocytes were studied in vitro. Primary hepatocytes obtained from male Sprague Dawley rats were cultured and incubated with PCP, 2,3,4,5-tetrachlorophenol (TCP), 2,4,5-trichlorophenol (TrCP), 2,4-dichlorophenol (DCP), or 4-chlorophenol (chlorophenol) for 1 hr at concn of 0 to 1X10-3 M. The effects on phase I and phase II metabolism of 7-ethoxycoumarin (7EC) were assessed by determining the concentrations for inhibiting 7-ethoxycoumarin-deethylase activity and depleting intracellular ATP content by 50 percent. The cultures were assayed for leakage of lactate dehydrogenase (LDH) into the medium. The EC50s for inhibiting phase I 7EC metabolism were: PCP, 37.5 uM; TCP, 34.6 uM; TrCP, 36.4 uM; DCP, 87.8 uM; and clorophenol, 215.2 uM. The corresponding EC50s for phase II 7EC metabolism were 6.5, 22.8, 22.0, 30.9, and 48.4 uM, respectively. The EC50s for depleting cellular ATP were: PCP, 6.4 uM; TCP, 18.4 uM; TrCP, 25.9 uM; DCP, 185.8 uM; and chlorophenol, 1334.1 uM. None of the compounds caused a significant leakage of LDH into the medium. When compared with published values of their octanol/water partition coefficients, the log of the EC50s were linearly correlated with the log of their partition coefficients. The /results indicate/ that short term exposure to chlorophenols severely disrupts the metabolic function of primary cultured rat hepatocytes at concentrations that do not affect cell membrane integrity. Primary cultures of rat hepatocytes are a suitable model for evaluating the short term toxicity of chlorinated phenols in vitro. [Aschmann C et al; Arch Toxicol 63 (2): 121-6 (1989)]**PEER REVIEWED**
  
• Phenol and the 19 isomers of chlorophenol were evaluated in the Microscreen Prophage Induction Assay to characterize the genotoxicity of these agents. Seven of the isomers induced prophage lambda in the presence of S9, with 2,3,4-trichlorophenol, 2,4,5-trichlorophenol, and 3,4,5-trichlorophenol being about ten times as potent as 2,3,6-trichlorophenol, 2,4,6-trichlorophenol, and pentachlorophenol. Medium potency was demonstrated by 2,3,4,5-tetrachlorophenol. Structurally, the more potent isomers had one or no chlorine atoms in the ortho position to the hydroxyl group. The less potent isomers had two chlorine atoms ortho to the hydroxyl group. None of the 20 compounds was mutagenic in Salmonella. However, the prophage induction results agreed with earlier results that most of these seven isomers were clastogenic, were associated with cancer and chromosomal aberrations in humans, and were carcinogenic in rodents. The /results/ suggest that the metabolism of the parent isomer to a chlorohydroquinone is an important step in the genotoxicity of these isomers. This chlorohydroquinone can form a chlorobenzosemiquinone in the presence of oxygen. Free radicals can then be produced that can cause DNA strand breaks, resulting in prophage induction in Escherichia coli or possibly the chromosomal aberrations associated with human exposure to chlorophenols. [DeMarini DM et al; Environ Mol Mutagen 15 (1): 1-9 (1990)]**PEER REVIEWED**
  
• An investigation was conducted to examine the competition of various chlorinated phenol congeners with the thyroxine (T4) binding site of transthyretin (TTR). Specifically, attempts were made to determine whether the T4 binding site of TTR could be occupied by hydroxylated chlorinated aromatic compounds using chlorinated phenol congeners as model compounds in a competition assay with (125)I labeled T4. 2,3-Dichlorobenzene, 3,4,3',4'-tetrachlorobiphenyl, 4-hydroxybiphenyl, and phenol were inefficient competitors. The chlorinated phenols which were tested were all competitors for the T4 binding site of TTR. The most effective competitor was pentachlorophenol (PCP), following in decreasing order by trichlorophenols, dichlorophenols, and monochlorophenols. When the chlorine was present in both ortho positions to the hydroxyl group, the competitor was more efficient. The relative affinity of binding of PCP to TTR was twice that of T4. PCP mainly decreased the affinity constant while the binding capacity was not altered. This indicated a competitive type of inhibition. PCP competed successfully with T4 sites on albumin as well with a relative affinity of 0.25. The binding of T4 to thyroid binding globulin was much less affected by PCP interference. /Results suggest/ that a specific interaction of chlorophenols exists with the T4 binding site of TTR. [van den Berg KJ; Chemico-Biological Interactions 76 (1): 63-75 (1990)]**PEER REVIEWED**
  
• The effect of pentachlorophenol (PCP) and its metabolite tetrachlorohydroquinone (TCH) were tested on growth, RNA, protein and ribosome syntheses, and ribosome content in yeast cells. Cells exposed to increasing concentrations of PCP show increasing inhibition to RNA and ribosome synthesis, and to cell growth. TCH causes a delay of the growth of the cell culture (prolongation of the lag phase) but does not cause inhibition. After treatment with TCH the maximum of the RNA synthesis was retarded, but subsequently reached nearly the same level as the untreated control cells. On ribosome synthesis and ribosome content, treatment with increasing concentrations of PCP, as well as of TCH, leads to a substantial decrease in ribosomal synthesis and, finally, total inhibition. Parallel to this, the content of free and membrane-bound ribosomes is diminished. PCP exhibits a stronger effect than TCH. The protein synthesis is only slightly reduced after treatment with PCP or TCH (with concentrations up to 20 ug/ml). [Ehrlich W et al; Ecotoxicol Environ Safety 13 (1): 7-12 (1987)]**PEER REVIEWED**
  
• Rainbow trout were exposed for 4 or 8 days to various types of toxicants, each applied to the test water at a high sublethal concentration. The activity of liver UDP-glucuronosyltransferase (UDP-GT) was assayed from the submitochondrial fraction using p-nitrophenol as an aglycone. Activity of UDP-GT was inhibited by 2,4,6-trichlorophenol, pentachlorophenol and dehydroabietic acid, all toxicants regularly found in effluents of the pulp and paper industry. The heavy metals cadmium and zinc, the polychlorinated biphenyl, Pyralene 3010, and chloroform did not affect UDP-GT activity. The slimicide N-methyl-dithiocarbamate (Vapam) significantly increased the enzyme activity. [Castr:en M, Oikari A; Comp Biochem Physiol 86 (2): 357-60 (1987)]**PEER REVIEWED**
  
• It is shown that p-tetrachlorohydroquinone (TCH), the metabolite of the environmental chemical pentachlorophenol (PCP), is more toxic to cultured CHO cells than PCP, and that it causes DNA single-strand breaks and/or alkali-labile sites at concentrations of 2-10 microgram/ml as demonstrated by the alkaline elution technique. [Ehrlich W; Mutat Res 244 (4): 299-302 (1990)]**PEER REVIEWED**
  
• Chronictoxicity test procedures (static, with renewal) were used to determine the chronic toxicity of sublethal concentrations of a technical formulation of pentachlorophenol (PCP) and pure pentachlorophenol to Daphnia magna. Test organisms 48 + or - 12 h old were exposed for their entire lifespan (ie, until death) to 0.01, 0.05, 0.1 and 0.5 mg technical PCP/L and 0.01, 0.087 and 0.1 mg pure PCP/L. Criteria used to assess chronic toxicity were mean time to appearance of the primiparous instar in the brood chamber, mean number of days to release of the first brood, mean number of broods produced per female, mean brood size per female, mean number of reproductive days, mean number of young produced per reproductive day per female and survivorship. Pentachlorophenol differentially affected maturation and reproduction but not survivorship or longevity. Mean number of broods produced per daphnid, length of the reproductive period, longevity and survivorship were insensitive criteria relative to mean time to appearance of the primiparous instar, time to release of first brood, brood size, and number of young produced per daphnid per reproductive day. Generally, there was little difference in toxicity of the three concentrations of pure PCP, for they significantly reduced mean brood size and rate of reproduction of young and significantly but differentially affected maturation. Technical PCP, at the highest concentration of 0.5 mg/L, significantly reduced mean brood size and the rate of production of young, and significantly delayed both time to appearance of the primiparous instar and release of the first brood. When differences in toxicity occurred, generally, pure PCP was more toxic than comparable concentrations of technical PCP. Although enhanced maturation was observed there was no compensatory reproduction. [Stephenson GL et al; Arch Environ Contam Toxicol 21 (3): 388-94 (1991)]**PEER REVIEWED**
  
• Chlorinated phenols represent a major component of hazardous oily and wood-preserving wastes that are widely distributed in chemical dumpsites throughout the United States. Pentachlorophenol has been reported to be highly embryolethal and embryotoxic in rats. However, data pertaining to the developmental toxicities of other important chlorophenols are limited. In this study, the toxicities of phenol, chlorophenol homologues and their isomers, selected phenyl acetates, anisoles, sodium phenates, and tetrachlorobenzoquinones (a total of 38 chemicals) were evaluated using cultures of Hydra attenuata. Developmental hazard index (A/D ratio) was determined for selected test chemicals (ie, those chemicals which resulted in an early toxic endpoint at the lowest whole-log concentration in the adult hydra assay). These same chemicals were evaluated at equimolar concentration in postimplantation rat whole embryo culture. Hydra attenuata and whole embryo culture studies demonstrated a linear relationship between toxicity and the degree of chlorine substitution with pentachlorophenol > 2,3,4,5-tetrachlorophenol > 2,3,5-trichlorophenol > 3,5-dichlorophenol > 4-chlorophenol > phenol. The developmental hazard index A/D ratios from the Hydra attenuata assay were approximately 1 for all of the chemicals tested. Findings from the whole embryo culture assay indicated similar results based on growth, gross morphology, and DNA and protein content of embryos. The results obtained in the Hydra attenuata and whole embryo culture assays suggest that the chlorinated phenols are not potent teratogens. The combination of Hydra attenuata and whole embryo culture may facilitate the rapid detection and ranking of hazardous chemicals associated with complex mixtures of chemical wastes. [Mayura K et al; Toxicol Appl Pharmacol 108 (2): 253-66 (1991)]**PEER REVIEWED**
  
• This study investigated impairment of oxidative phosphorylation in mitochondria isolated from the liver of hexachlorobenzene treated rats. Partial and reversible uncoupling of the phosphorylative process was found in liver mitochondria from rats dosed with hexachlorobenzene for 60 days. Pentachlorophenol, endogenously formed by hexachlorobenzene metabolism was detected in the mitochondria at a concn of 0.3-0.4 nmol/mg protein. Based on the effect of pentachlorophenol, added in vitro at a similar concn to that found in vivo, it was concluded that the uncoupling of oxidative phosphorylation under the experimental conditions was almost completely due to the presence of pentachlorophenol. [Trenti T et al; IARC Sci Pub 77: 329-31 (1986)]**PEER REVIEWED**
  
• This study investigated the extent of impairment in function parameters of liver mitochondria from rats treated for 60 days with hexachlorobenzene. A constant amount of mitochondrial uncoupling was found throughout the treatment period. At the same time a nearly constant amount of pentachlorophenol was detected in these mitochondria. In contrast, the level of mitochondrial porphyrins increased progressively. There was good correlation between the concentration of mitochondrial pentachlorophenol and the degree of uncoupling of oxidative phosphorylation. [Trenti T et al; IARC Sci Pub 77: 457-9 (1986)]**PEER REVIEWED**
  

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Human Toxicity Values

• None found

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Non-Human Toxicity Values

• LD50 Rat male oral 146 mg/kg [Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989., p. 1126]**PEER REVIEWED**
  
• LD50 Rat female oral 175 mg/kg [Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989., p. 1126]**PEER REVIEWED**
  
• LD50 Rat oral 210 mg/kg [Hartley, D. and H. Kidd (eds.). The Agrochemicals Handbook. 2nd ed. Lechworth, Herts, England: The Royal Society of Chemistry, 1987., p. A473]**PEER REVIEWED**
  
• LD50 Rat dermal 96-330 mg/kg [American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 1177]**PEER REVIEWED**
  

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Absorption, Distribution and Excretion

• Rapid absorption of pentachlorophenol has been reported in rodents, monkeys, & humans following oral, dermal, or inhalation exposure. ... The major tissue deposits vary somewhat between species. In humans whose deaths were not related to pentachlorophenol exposure, the liver (containing pentachlorophenol residues of 0.067 ug/g), kidney, brain, spleen, & fat (0.013 ug/g) appeared to be major deposition sites. In the mouse, the gall bladder is a principal storage site. In the rat, it is the kidney. [National Research Council. Drinking Water and Health, Volume 6. Washington, D.C.: National Academy Press, 1986., p. 385]**PEER REVIEWED**
  
• WHEN WORKER EXPOSURE TO PENTACHLOROPHENOL AT WOOD TREATMENT PLANT WAS MEASURED OVER 5 MO PERIOD, SERUM & URINE LEVELS ... WERE 348.4 TO 3963 UG/L & 41.3 TO 760 UG/L, RESPECTIVELY. PENTACHLOROPHENOL RESIDUES IN WORKPLACE AIR WERE IN THE RANGE OF 5.1 TO 15275.1 NG/CU M. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V20 309 (1979)]**PEER REVIEWED**
  
• (14)C-PCP WAS ADMIN TO MICE BY SC OR IP INJECTION. MOST OF THE ACTIVITY (72-83%) WAS EXCRETED IN URINE IN 4 DAYS; ABOUT HALF, IN 24 HR; & ONLY TRACE (0.05%), IN EXPIRED AIR. HIGH ACTIVITY OBSERVED IN GALLBLADDER & ITS CONTENTS, WALL OF STOMACH FUNDUS, CONTENTS OF GI TRACT & LIVER. [Menzie, C. M. Metabolism of Pesticides, An Update. U.S. Department of the Interior, Fish, Wild-life Service, Special Scientific Report - Wildlife No. 184, Washington, DC: U.S. Government Printing Office, l974., p. 287]**PEER REVIEWED**
  
• ENTEROHEPATIC CIRCULATION OF PENTACHLOROPHENOL OCCURS IN MONKEYS & MICE. IN RATS, IT IS FOUND MAINLY IN PLASMA PROTEIN; LIVER & KIDNEY HAVE HIGHEST TISSUE CONCN. PLASMA HALF-LIVES AT 10 MG/KG BODY WT DOSE WERE ABOUT 15 HR IN RATS & 78 HR IN MACACA MULATTA MONKEYS. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V20 316 (1979)]**PEER REVIEWED**
  
• UNLESS RENAL & LIVER FUNCTIONS ARE IMPAIRED, PENTACHLOROPHENOL IS RAPIDLY ELIMINATED FROM BLOOD & TISSUES. [Morgan, D.P. Recognition and Management of Pesticide Poisonings. EPA 540/9-80-005. Washington, DC: U.S. Government Printing Office, Jan. 1982., p. 22]**PEER REVIEWED**
  
• PENTACHLOROPHENOL HAS BEEN DETECTED IN HUMAN BLOOD PLASMA AT LEVELS OF 15.69 TO 15.86 UG/L IN HEMODIALYZED PATIENTS & 15.0 UG/L IN PERSONS USED AS CONTROL. IT ALSO HAS BEEN DETECTED IN URINE, SEMINAL FLUID (20-70 UG/KG) & FINGERNAILS OF NON-OCCUPATIONALLY EXPOSED INDIVIDUALS. PENTACHLOROPHENOL WAS FOUND IN 85% OF 416-418 SAMPLES OF URINE COLLECTED FROM GENERAL POPULATION ... MAX LEVEL WAS 193 UG/L & MEAN LEVEL 6.3 UG/L. ... URINE SAMPLES TAKEN AT 25 FACTORIES USING PENTACHLOROPHENOL ... SHOWED THAT AVG WORKER'S EXPOSURE TO PENTACHLOROPHENOL IN AIR WAS 0.013 MG/CU M, WITH MAX RANGE OF 0.004-1.000 MG/ CU M, & LEVEL IN URINE RANGED FROM 0.12 TO 9.68 MG/L. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V20 308 (1979)]**PEER REVIEWED**
  
• Small amounts have been shown to cross the placenta. [Shepard, T.H. Catalog of Teratogenic Agents. 5th ed. Baltimore, MD: The Johns Hopkins University Press, 1986., p. 443]**PEER REVIEWED**
  
• Plasma and urinary pentachlorophenol was measured in 209 workers who had occupational exposure to wood preservatives containing this compound and 101 workers not exposed occupationally to pentachlorophenol. Workers were examined for chloracne and blood concentrations of bilirubin, gamma-glutamyltransferase, cholesterol and high-density lipoproteins were determined. All the occupationally exposed groups showed evidence of pentachlorophenol absorption; highest mean concentrations were found in timber treatment operatives (6.0 mmol/l for plasma and 274 nmol/mmol of creatinine for urine). [Jones RD et al; Hum Toxicol 5 (3): 189-94 (1986)]**PEER REVIEWED**
  
• Pentachlorophenol was given orally to ... volunteers at single doses of 3.9, 4.5, 9, and 18.8 mg. Daily urinary excretion of pentachlorophenol and pentachlorophenol conjugated to glucuronic acid was monitored using gas chromatography with electron capture detection. Based on first order elimination kinetics an elimination half-life of 20 days was derived. To eliminate interference by the uncontrolled absorption of pentachlorophenol from the environment 0.98 mg (13)C-pentachlorophenol was taken by one of the volunteers. Pentachlorophenol levels in urine and plasma were determined using mass spectrometry with negative chemical ionization. An elimination half-life of 17 days was found in both urine and blood. The collected data were used to calculate the clearance of pentachlorophenol: a value of 0.07 m1/min was found. The long elimination half-life of pentachlorophenol is explained by the low urinary clearance due to the high plasma protein binding (> 96%) and the tubular reabsorption. The pH-dependency of the elimination of pentachlorophenol was investigated, and a distinct increase in the daily excretion was observed following alkalinization by oral administration of sodium bicarbonate. In order to elucidate the role of the enterohepatic circulation as a possible pool for pentachlorophenol in humans, the bile of cholelithiasis patients with postoperative T-drainage was investigated for pentachlorophenol and compared with the corresponding urine and plasma levels, but no accumulation of pentachlorophenol in the enterohepatic circulation could be observed. The daily elimination and plasma levels of pentachlorophenol in a group of individuals without a specific exposure were found to range from 10 to 48 ug/day and 19 to 36 ug/1, respectively. [Uhl S et al; Arch Toxicol 58 (3): 182-6 (1986)]**PEER REVIEWED**
  
• Urine from 230 Finnish sawmill workers exposed to a combination of 2,3,4,6-tetrachlorophenol (80%), 2,4,6-trichlorophenol (10-20%), and pentachlorophenol (5%), was analyzed for the sum of the three chemicals as chlorophenols. Samples were collected at the end of the work shift. Workers were divided into the following exposure groups according to work tasks: primarily skin exposure (n= 112), primarily respiratory tract exposure (n= 34), and equal exposure by both routes (n= 84). Air concentrations at the workplace and amount of time spent with skin contact were not studied. There was no control group; values were compared to the nonexposed Finnish population level of < 0.1 umol/l. Skin absorption was the most effective route of exposure as reflected by urinary chlorophenol concentrations. The median concentration in workers with skin absorption was 7.8 umol/l (range 0.1 to 210.9 umol/l) and was significantly different from that in workers with the respiratory tract as the main route of exposure (median concentration 0.9 umol/l; range 0.1 to 13.3 umol/l; p< 0.001) and from those with both routes of equal importance (1.4 umol/l; range 0.1 to 47.8 umol/l; p< 0.001). /Tri-, Tetra-, and Pentachlorophenols/ [Lindroos L et al; Int Arch Occupat Environ Health 59 (5): 463-7 (1987)]**PEER REVIEWED**
  
• The compounds are readily absorbed from the gastroenteric tract and from parenteral sites of injection. /Chlorophenols/ [Clayton, G.D., F.E. Clayton (eds.) Patty's Industrial Hygiene and Toxicology. Volumes 2A, 2B, 2C, 2D, 2E, 2F: Toxicology. 4th ed. New York, NY: John Wiley & Sons Inc., 1993-1994., p. 1615]**PEER REVIEWED**
  
• Plasma half-life in man is 30.2 + or - 4.0 hr. Half-lives for elimination of pentachlorophenol and pentachlorophenol-glucuronide from the urine are 33.1 + or - 4.5 and 12.7 + or - 5.4 hr, respectively. [USEPA; Ambient Water Quality Criteria Doc: Pentachlorophenol p.C-18 (1980) EPA 440/5-80-065]**PEER REVIEWED**
  
• The dependence of bats in Britain on houses as roosts may result in them being exposed to pesticides used in remedial timber treatments. Pentachlorophenol and permethrin are used as a fungicide and a insecticide for timber treatment, respectively. The present study investigated toxicity and distribution in body tissues of these two pesticides in pipistrelle bats. Four groups of nine to ten bats were kept in separate outdoor flight enclosures and were provided with roost boxes treated with either pentachlorophenol only, permethrin, pentachlorophenol/permethrin mixture or solvent only (control). At the start of the experiment, mean (: standard error) pentachlorophenol and permethrin concentrations on the surface of wooden blocks that had been treated in the same way as roost boxes were 69.32 : 6.76 mg/g (n = 6) and 3.3 : 1.6 mg/g (n = 3), respectively. All bats exposed to pentachlorophenol and pentachlorophenol/permethrin treated boxes died within 24 and 120 hr, respectively; nine out of the ten controls survived the 32 day experimental period (p< 0.001; both groups compared with control). Bats exposed to permethrin treated boxes survived as well as controls. Mean (: standard error) carcass pentachlorophenol concentration (excluding deposits on fur) of bats exposed to pentachlorophenol and pentachlorophenol/permethrin treated boxes was 13.11 : 2.52 ug/g body wt (n = 20). Pentachlorophenol burdens on fur were positively correlated with total weight of Pentachlorophenol in the carcass (p< 0.001). Pentachlorophenol was present in fat depots, liver, kidney and the remainder of the body which, despite containing low pentachlorophenol concentrations, was the main pentachlorophenol reservoir (66.4 : 5.0% of carcass pentachlorophenol load; n = 20). Total pentachlorophenol in the carcass was significantly correlated with lipid weight (p< 0.005). Permethrin was not detectable in body washes and tissues of bats exposed to pentachlorophenol/permethrin mixture or permet. [Shore RF et al; Environ Pollut 73 (2): 101-18 (1991)]**PEER REVIEWED**
  
• A pilot study was conducted to determine the overall efficiency of transdermal penetration of pentachlorophenol and tetrachlorophenol applied to human cadaver skin. Two commercially available wood preservatives were tested, one diesel oil based and the other a water based product. To simulate human exposure conditions at the workplace, small doses were used. The objective was to document the portion of applied dose which permeated the skin and to examine the effect of vehicle or formulation on the relative and absolute absorption of the chlorinated compounds. The penetration of the diesel oil preparations was 62% for pentachlorophenol and 63% for tetrachlorophenol. In the case of the aqueous based preparation, penetration was 16% for sodium-pentachlorophenate and 33% for sodium tetrachlorophenate. The incomplete recovery of each compound may have been due in part to the irreversible binding or unfavorable partitioning of the chlorophenols which would be consistent with the lipophilic character of these compounds. [Horstman SW et al; J Environ Sci Health A24 (3): 229-42 (1989)]**PEER REVIEWED**
  
• The excretion and conjugation of chlorophenols were studied in workers exposed to 2,4,6-tri-, 2,3,4,6-tetra-, and pentachlorophenolates, the main components of the chlorophenolate product manufactured by direct chlorination of phenol. The workers were exposed in two different saw mills in which sodium chlorophenolate was used for treatment of lumber during the warm season. Urine specimens were collected at the end of the treatment season as well as at the start of a new treatment period in the spring. Serum specimens were collected towards the end of the treatment period. Total and unconjugated chlorophenols were analyzed with a GC method. The maximal concentrations of urinary 2,4,6-tri-, 2,3,4,6-tetra- and pentachlorophenol at the end of the lumber-treatment period were 1-11.8, 3.4-17.3, and 0.2-0.9 umol/l, respectively, and the average apparent half-times calculated using a one compartment model were 18 hr, 4.3 days and 16 days, respectively. For 2,3,4,6-tetrachlorophenol, the data of some subjects showed a better fit with a two compartment model; the corresponding half-times were 5.3 and 26 days. During the continuous-exposure period the average serum levels of tetra- and pentachlorophenol were rather similar before and after the working day: 2.79 + or - 1.78 umol/l for tetrachlorophenol and 0.85 + or - 0.4 umol/l for pentachlorophenol. Renal clearance values for tetra- and pentachlorophenol were related to urine flow and indicated tubular reabsorption. At low concentrations, sulfate conjugation was dominant. With increasing chlorophenol concentrations the proportion of glucuronide conjugation was increased, especially for pentachlorophenol. [Pekari K et al; Int Arch Occup Environ Health 63 (1): 57-62 (1991)]**PEER REVIEWED**
  
• 1. Interspecies variability in the metabolism of pentachlorophenol (PCP) was investigated by exposing rainbow trout, fathead minnows, sheepshead minnow, firemouth, and goldfish to water-borne (14)C-PCP for 64 hr. 2. The amounts of metabolites in bile and exposure water were species-dependent; all of the metabolites excreted into the water were sulfate conjugates while bile was enriched in glucuronide conjugates. 3. Biliary excretion accounted for less than 30% of the total PCP metabolites. 4. Biliary metabolites alone were a poor indication of the metabolites produced and of the major routes of elimination. [Stehly GR, Hayton WL; Xenobiotica 19 (1): 75-81 (1989)]**PEER REVIEWED**
  

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Metabolism/Metabolites

• ... MAJOR METABOLITE OF HCB /HEXACHLOROBENZENE/ ... . [The Royal Society of Chemistry. Foreign Compound Metabolism in Mammals. Volume 6: A Review of the Literature Published during 1978 and 1979. London: The Royal Society of Chemistry, 1981., p. 327]**PEER REVIEWED**
  
• FOLLOWING SINGLE ORAL DOSE OF PENTACHLORO-(14)C-BENZENE (0.5 MG/KG) TO RHESUS MONKEYS ... /7% WAS EXCRETED/ AS PENTACHLOROPHENOL ... IN URINE. [The Royal Society of Chemistry. Foreign Compound Metabolism in Mammals. Volume 6: A Review of the Literature Published during 1978 and 1979. London: The Royal Society of Chemistry, 1981., p. 346]**PEER REVIEWED**
  
• PENTACHLOROPHENOL ... IS DECHLORINATED IN VIVO & IN VITRO IN RAT TO TETRA- & TRI-CHLOROHYDROQUINONE ... DECHLORINATION IS MEDIATED BY LIVER-MICROSOMAL ENZYMES, & THEIR ACTIVITY IS ENHANCED BY PRE-TREATMENT WITH SEVERAL WELL-KNOWN INDUCERS OF CYTOCHROME P450. ... PHARMACOKINETIC STUDY OF SINGLE ORAL DOSAGE (0.1 MG/KG) ... IN HUMAN SUBJECTS ... REVEALED NO METABOLITES WERE DETECTED APART FROM GLUCURONIDE OF PCP (ABOUT 12%). [The Royal Society of Chemistry. Foreign Compound Metabolism in Mammals. Volume 6: A Review of the Literature Published during 1978 and 1979. London: The Royal Society of Chemistry, 1981., p. 327]**PEER REVIEWED**
  
• BACTERIAL ISOLATE, RELATED TO SAPROPHYTIC CORYNEFORM BACTERIA, WAS ABLE TO METABOLIZE PENTACHLOROPHENOL AS SOLE SOURCE OF CARBON & ENERGY. PENTACHLOROPHENOL WAS RAPIDLY METABOLIZED TO CO2. IN CULTURES OF TRICHODERMA VIRGATUM, PENTACHLOROPHENOL WAS METHYLATED TO FORM PENTACHLOROANISOLE. SIMILARLY, PENTACHLOROANISOLE WAS FORMED FROM PENTACHLOROPHENOL BY PENICILLIUM SP & CEPHALOASCUS FRAGRANS. [Menzie, C. M. Metabolism of Pesticides, An Update. U.S. Department of the Interior, Fish, Wild-life Service, Special Scientific Report - Wildlife No. 184, Washington, DC: U.S. Government Printing Office, l974., p. 288]**PEER REVIEWED**
  
• THE PROTOPORPHYRIN ENZYME PEROXIDASE, DETECTED IN SNAILS, CATALYZED OXIDATION OF PENTACHLOROPHENOL TO 2,2',3,3',5,5',6,6'-OCTACHLOROBIPHENYLQUINONE. [Menzie, C. M. Metabolism of Pesticides, An Update. U.S. Department of the Interior, Fish, Wild-life Service, Special Scientific Report - Wildlife No. 184, Washington, DC: U.S. Government Printing Office, l974., p. 287]**PEER REVIEWED**
  
• ... MOST OF PENTACHLOROPHENOL TRANSFERRED TO HEPATOPANCREAS /IN GOLDFISH/ WAS DETOXIFIED BY SULFATE CONJUGATION OR BY DECOMPOSITION. EXCRETION ... WAS IN FORM OF CONJUGATE IDENTIFIED AS PENTACHLOROPHENYLSULFATE. [Menzie, C.M. Metabolism of Pesticides, Update II. U.S. Department of the Interior, Fish Wildlife Service, Special Scientific Report - Wildlife No. 2l2. Washington, DC: U.S. Government Printing Office, 1978., p. 221]**PEER REVIEWED**
  
• The metabolism of pentachlorophenol is generally similar in mammalian species. In rodents, more than 40% is excreted in urine unchanged. The remainder is excreted as tetrachlorohydroquinone and glucuronide conjugates of pentachlorophenol. In limited studies of humans, pentachlorophenol, tetrachlorohydroquinone, & pentachlorophenol glucuronide have been found in urine. In vivo retention of pentachlorophenol by lipid-containing tissues may be attributable to conjugation with fatty acids. [National Research Council. Drinking Water and Health, Volume 6. Washington, D.C.: National Academy Press, 1986., p. 385]**PEER REVIEWED**
  
• Unchanged pentachlorophenol is excreted in the urine of rabbit, rat, mouse, and monkey. In addition to free pentachlorophenol, rats excrete tetrachloro-p-hydroquinone and trichloro-p-hydroquinone. ... Both metabolites as well as the parent cmpd are excreted free and as glucuronides. [Hayes, Wayland J., Jr. Pesticides Studied in Man. Baltimore/London: Williams and Wilkins, 1982., p. 474]**PEER REVIEWED**
  
• The biotransformation of pentachlorophenol in man and animals takes place by conjugation, hydrolytic dechlorination, and reductive dechlorination. Further species dependent reactions are oxidation and methylation. The reaction with glutathione results in the formation of conjugates and cleavage of glycine and glutamate gives cysteine conjugates. Acetylation of the amino group of the cysteinyl moiety in mammals gives mercapturic acids. The metabolic pathways leading to dechlorinated derivatives may be mediated by the reaction with glutathione as the presence of the N-acetyl-S-(pentachlorophenyl)cysteine. [Renner G, Mucke W; Toxicol Environ Chem 11 (1): 9-29 (1986)]**PEER REVIEWED**
  
• The metabolism of pentachlorophenol and its covalent binding to protein and DNA were tested in the microsomes of Wistar rats of both sexes pretreated with hexachlorobenzene, phenobarbital, 3-methylcholanthrene, or isosafrole. Pentachlorophenol when incubated with microsomes, was converted into tetrachloro-1,2-hydroquinone and tetrachloro-1,4-hydroquinone. Isosafrole increased the rate of conversion 7 times as compared to control microsomes, while hexachlorobenzene, pentachlorophenol and 3-methylcholanthrene increased the rate of conversion 2 to 3 times. The fact that pentachlorophenol and hexachlorobenzene accounted for the production of tetrachloro-1,4-hydroquinone and tetrachloro-1,2-hydroquinone in a ratio of about 2, as compared to a ratio of about 1.3 for 3-methylcholanthrene and isosafrole, and the fact that this ratio decreased with increasing concentrations of pentachlorophenol in microsomes from hexachlorobenzene treated rats, were indicative of the involvement of the various cytochrome p450 isoenzymes. The covalent binding of pentachlorophenol to protein was inhibited by ascorbic acid, with a subsequent increase in the production of tetrachlorohydroquinones. The rate of covalent protein binding was constant, regardless of variation in the rate of conversion observed in the mirosomes of rats treated with various inducers. DNA binding was conversion dependent and was lower than protein binding. The addition of DNA did not affect the formation of soluble metabolites. [Van Ommen B et al; Chemico-Biol Interact 60 (1): 1-11 (1986)]**PEER REVIEWED**
  
• The metabolism of pentachlorophenol in animals and man was reviewed. Tetrachlorophenols, 2,3,5,6-tetrachloro-1,4-benzoquinone, 2,3,4-trichlorophenol, 2,3,5-trichloro-1,4-hydroquinone, and their glucuronide conjugates were found in animals and man. Also identified were pentachlorophenylacetate, pentachloroanisole, and pentachlorophenylsulfate. The biotransformation of pentachlorophenol in man and animals takes place by conjugation, hydrolytic dechlorination, and reductive dechlorination. Further species dependent reactions are oxidation and methylation. The reaction with glutathione results in the formation of conjugates and cleavage of glycine and glutamate gives cysteine conjugates. Acetylation of the amino group of the cysteinyl moiety in mammals gives mercapturic acids. The metabolic pathways leading to dechlorinated derivatives may be mediated by the reaction with glutathione as the presence of the N-acetyl-S-(pentachlorophenyl)cysteine would indicate. The results of metabolic in vivo studies on hexachlorobenzene, pentachloronitrobenzene, pentachlorobenzene, and pentachlorophenol indicate that one pathway stems from hexachlorobenzene and pentachloronitrobenzene via sulfur containing conjugates to thiophenolic derivatives and to chlorinated benzenes, primarily to pentachlorobenzene. Another pathway transforms pentachlorophenol to less chlorinated phenols. The authors state that pentachlorophenol is a metabolite of various environmental chemicals and is itself metabolized. Therefore there is no direct relationship between the level of pentachlorophenol in body fluids and the degree of exposure. [Renner G, Mucke W; Toxicological and Environmental Chemistry 11 (1): 9-29 (1986)]**PEER REVIEWED**
  

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TSCA Test Submissions

• None found

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Footnotes

¹ Source: the National Library of Medicine's Hazardous Substance Database, 10/28/2007.