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In vitro immunomodulation by pentachlorophenol in phagocytes from an estuarine teleost, Fundulus heteroclitus, as measured by chemiluminescence activity.

Chemiluminescence (CL) was used to assay effects of pentachlorophenol (PCP) on the production of reactive oxygen intermediates (ROIs) generated by leukocytes from an estuarine teleost, Fundulus heteroclitus. Two parameters were measured during the phagocytically-induced respiratory burst: peak CL (maximal value) and total CL (temporal summation of induced values). Phagocytes obtained from the pronephros were incubated in the presence of sublethal doses of analytical (A-) or technical (T-) grades of PCP. Technical PCP has been reported to be more highly immunosuppressive than A-PCP in mammals; this effect was attributed to dioxins and other contaminants produced during manufacture. In this fish, both grades of the compound produced significant dose-dependent inhibition of peak and total CL. However, there were few significant differences between the effects of the two PCP grades on the magnitude of the CL responses at identical, sublethal concentrations, although T-PCP did produce a more marked reduction in the relative level of leukocytic CL as a function of dose than did A-PCP. Because of the probable roles of ROIs in antimicrobial blood cell-mediated mechanisms, reduced CL activity was interpreted as an indication of xenobiotic-induced immunosuppression.

Adjuvants, Immunologic↗

Ultrastructural morphometric investigations on rat liver of young and adult rats after treatment with technical pentachlorophenol (PCP).

Age-dependent effects of technical pentachlorophenol (PCP) on male rat livers were investigated after a 15 day treatment with PCP, 30 mg/kg/d body weight. The liver tissues were investigated morphometrically at light and electron microscopical levels. Statistically significant alterations of nuclei and organelles of the hepatocytes were described.

Adipose Tissue↗

Effects of pentachlorophenol and 2,4,6-trichlorophenol on the disposition of sulfobromophthalein and respiration of isolated liver cells.

The effect of pentachlorophenol (PCP) and 2,4,6-tricholorphenol (2,4,6-T) on the disposition of the hepatodiagnostic dye, sulfobromophthalein (BSP) has been studied in isolated liver cells. PCP (4-6 microM) as well as 2,4,6-T (50-100 microM) interferes with the disposition of BSP. The main effect apparently occurs at the secretion step as both drugs severely impair the release of the glutathione conjugate of BSP into the medium. As a consequence, BSP and its conjugate accumulate in the cell. High doses of PCP did not increase the release of lactate dehydrogenase from the hepatocytes. Concentrations of the two phenols which interfere with the secretion of BSP also completely uncouple the oxidative phosphorylation of hepatocellular mitochondria. The dysfunction of liver cells described here may therefore be explained by the effect of PCP and 2,4,6-T on the energy production of the cells. The higher toxicity of PCP as compared to 2,4,6-T observed in our system corresponds well with the higher LD50 of the latter compound.

Animals↗

Pharmacokinetics of pentachlorophenol in man.

Pentachlorophenol (PCP) was given orally to three volunteers at single doses of 3.9, 4.5, 9, and 18.8 mg. Daily urinary excretion of PCP and PCP conjugated to glucuronic acid was monitored using gas chromatography with electron capture detection (GC/ECD). Based on first-order elimination kinetics an elimination half-life of 20 days was derived. To eliminate interference by the uncontrolled absorption of PCP from the environment 0.98 mg 13C-PCP was taken by one of the volunteers. PCP levels in urine and plasma were determined using mass spectrometry (GC/MS) 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 PCP: a value of 0.07 ml/min was found. The long elimination half-life of PCP is explained by the low urinary clearance due to the high plasma protein binding (greater than 96%) and the tubular reabsorption. The pH-dependency of the elimination of PCP 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 PCP in humans, the bile of cholelithiasis patients with postoperative T-drainage was investigated for PCP and compared with the corresponding urine and plasma levels, but no accumulation of PCP in the enterohepatic circulation could be observed. The daily elimination and plasma levels of PCP in a group of individuals without a specific exposition were found to range from 10 to 48 micrograms/day and 19 to 36 micrograms/1, respectively.

Adult↗

Determination of total pentachlorophenol in the urine of workers. A method incorporating hydrolysis, an internal standard and measurement by liquid chromatography.

Free pentachlorophenol (PCP) represents a small and variable fraction of total PCP excreted in the urine of exposed workers. A method incorporating hydrolysis is essential to be able to relate PCP excretion to absorbed dose. 3,5-Dichloro-2,4,6-tribromophenol (DTP) is added as an internal standard to a urine sample which is then acidified and steam-distilled. The distillate is made alkaline and extracted with methylene chloride to remove interferences. The distillate is then acidified and the phenols extracted into methylene chloride. The extract is evaporated, redissolved in acetonitrile and the PCP is measured using high pressure liquid chromatography (HPLC) using a 15 X 0.46 cm Spherisob-ODS 5 microns column with isocratic elution (H2O:CH3CN:CH3CO2H, 45:55:0.3 v/v). Detection is by fixed wavelength detector at 313 nm and calculation by the method of internal standardization. The biological threshold value used to trigger action to reduce exposure is 7 mg/l (corrected to a specific gravity of 1.024).

Chlorophenols↗

[Investigations on neurotoxicity of chemical substances at the workplace. II. Determination of the motor and sensory nerve conduction velocity in persons occupationally exposed to pentachlorophenol (author's transl)].

We examined eighteen workers (three women, 15 men) in a pentachlorophenol (PCP) processing factory, with a mean activity of 12 years. PCP in blood and urine samples was analyzed by gas chromatography. To evaluate the peripheral nervous system the maximal motor as well as sensory nerve conduction velocities of the ulnar and/or median nerve were measured. The PCP-levels in plasma ranged between 0.02 and 1.5 ng/l, median 0.25 ng/l, and in urine between 13 and 1,224 micrograms/l, median 112 micrograms/l, or between 11 and 2,111 micrograms/g creatinine, median 111 micrograms/g creatinine. The median values of the neurophysiological parameters showed a mild degree of slowing in the PCP-collective. In the case of the sensory nerve conduction velocities, this decrease was significant. A dose-effect relationship between internal PCP-load and the different nerve conduction velocities could not be demonstrated. The individual evaluation of the toxicological and neurophysiological results gave hints that in some cases decreased nerve conduction velocity is caused by chronic exposure to PCP.

Adult↗

Sister chromatid exchange and chromosomal breakage in pentachlorophenol (PCP) exposed workers.

A cytogenetic study was performed on 20 healthy workers exposed to pentachlorophenol (PCP) in concentrations ranging from 1.2 to 180 micrograms/m3 (Maximum Concentration at the workplace is 500 micrograms/m3) for 3 to 34 years. PCP was determined in the blood plasma of all probands, yielding concentrations between 23 and 775 micrograms/l (Biological Tolerance Value is 1000 micrograms/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.

Adult↗

Physiological properties and substrate specificity of a pentachlorophenol-degrading Pseudomonas species.

A bacterial strain capable of utilizing pentachlorophenol (PCP) as sole source of carbon and energy for growth was isolated from enrichment cultures containing 100 mg/l PCP in a mineral salts medium inoculated with contaminated soil from a lumber treatment waste site. The isolate, designated strain SR3, was identified as a species of Pseudomonas by virtue of its physiological and biochemical characteristics. Mineralization of PCP by Pseudomonas sp. strain SR3 was demonstrated by loss of detectable PCP from growth medium, stoichiometry of chloride release (5 equivalents of chloride per mole of PCP), and formation of biomass consistent with the concentration of PCP mineralized. PCP-induced cells of strain SR3 showed elevated rates of oxygen consumption in the presence of PCP, and with different chlorinated phenols, with complete degradation of 2,3,5,6-, 2,3,6-, 2,4,6-, 2,4-, and 2,6-chloro-substituted phenols. Concentrations of PCP up to 175 mg/liter supported growth of this organism, but maximal rates of PCP removal were observed at a PCP concentration of 100 mg/liter. Based on its degradative properties, Pseudomonas sp. strain SR3 appears to have utility in bioremediation of soil and water contaminated with PCP.

Biodegradation, Environmental↗

Molecular analysis of pentachlorophenol degradation.

A limited number of microorganisms have been described for their ability to partially degrade pentachlorophenol (PCP), or to completely mineralize it. Several years ago we chose one of these microorganisms, Flavobacterium sp. strain ATCC 39723, for use in a detailed molecular analysis of the catabolism of PCP. This strain was chosen because it had previously been studied in great detail for its growth characteristics in relation to degradation of PCP. In this paper we provide an overview of the degradation pathway of PCP to 2,6-dichloro-p-hydroquinone by Flavobacterium. The specific biochemical reactions and the genes encoding the enzymes are reviewed. The successful transformation and site specific mutagenesis of Flavobacterium, as well as the discovery of two new pcp alleles is also presented.

Amino Acid Sequence↗

Effect of pH on the accumulation kinetics of pentachlorophenol in goldfish.

The kinetics of accumulation of pentachlorophenol (PCP) at various pH values were investigated to explore how pH-dependent accumulation might influence PCP toxicity. Goldfish (Carassius auratus) were exposed to 5 micrograms PCP/L in a static system buffered with 7.5 mM bicine or N,N-bis(2-hydroxyethyl)-2-aminoethane sulfonic acid (BES) at pH 7.0, 8.0, or 9.0. The amount of PCP in the fish, concentration of PCP in water, and the total amount of metabolites in the system were measured after exposure of fish from 1 to 96 hr. Equations for these variables based on a two compartment pharmacokinetic model were fitted simultaneously to the data using NONLIN, which uses an iterative nonlinear least squares technique. Uptake clearance, metabolic clearance, and apparent volume of distribution of PCP decreased as pH increased. The decrease in PCP accumulation with increased pH was not due solely to a pH-induced decrease in uptake. In addition, the distribution of PCP within the fish was altered by changes in the external pH. The pH-associated changes in distribution may have altered access of PCP to sites of metabolism, thereby altering the metabolic clearance. The pH-related changes in the pharmacokinetics of PCP resulted in a decrease in its bioconcentration factor with an increase in pH and account both for the decreased capacity of the fish to accumulate PCP and for its reduced LC50.

Animals↗

Pentachlorophenol measurements in body fluids of people in log homes and workplaces.

Human exposure to pentachlorophenol (PCP) was evaluated in the normal population (controls), residents of PCP-treated log homes, and persons exposed primarily in the workplace. Blood and urine samples were analyzed by gas chromatography after extraction and acetylation. For 34 controls, serum PCP values ranged from 15-75 ppb with a mean of 40 ppb. For 123 residents of log homes, serum levels ranged from 69-1,340 ppb with a mean of 420 ppb. In such homes, serum levels for children were significantly higher than those for parents, averaging 1.8 times greater. Serum and urine values for workers varied widely, depending on the workplace, with serum levels ranging from 26 to 84,900 ppb of PCP. Urinary concentrations when corrected for creatinine values correlated well (r = 0.92) with serum concentrations. Coating PCP-treated logs of home interiors with a sealant reduced serum PCP levels in the residents.

Adolescent↗

Pentachlorophenol: environmental partitioning and human exposure.

This paper uses a six compartment environmental partitioning model to explore the transport and accumulation of pentachlorophenol (PCP) within and between various environmental media. Environmental concentrations were then used to estimate the amount of PCP entering the food chain and the long-term, average daily intake of PCP by the general population of the U.S. Results show that PCP partitions mainly into soil (96.5%) and that the food chain, especially fruits, vegetables, and grains, accounts for 99.9% of human exposure to PCP. The long-term, average daily intake of PCP is estimated to be 16 micrograms/day, which agrees well with a previous estimate of 19 micrograms/day (Geyer et al. 1987).

Chlorophenols↗

Effects of phenol, 2,4-dimethylphenol, 2,4-dichlorophenol, and pentachlorophenol on embryo, larval, and early-juvenile fathead minnows (Pimephales promelas).

Embryos of fathead minnows were more resistant to phenol, 2,4-dimethylphenol (2,4-DMP), 2,4-dichlorophenol (2,4-DCP), and pentachlorophenol (PCP) than were larval or juvenile life stages. Growth of 28-day-old fish was the most sensitive indicator of stress during exposures to phenol, 2,4-DMP, and PCP, whereas survival was the most sensitive indicator of toxic effects from 2,4-DCP exposure. Based on these effects, the estimated maximum acceptable toxicant concentration for fathead minnows in Lake Superior water lies between 1,830 and 3,570 micrograms/L for phenol; 1,970 and 3,110 micrograms/L for 2,4-DMP; 290 and 460 micrograms/L for 2,4-DCP; and 44.9 and 73.0 micrograms/L for PCP.

Animals↗

Clinical findings in workers exposed to pentachlorophenol.

Comparative findings are presented on the health and exposure status of groups of individuals in Hawaii with and without occupational exposure to pentachlorophenol (PCP). Occupational exposure to PCP occurred through employment at firms engaged in the treatment of wood with either PCP alone or PCP plus other compounds as preservative chemicals. Mean serum levels were 0.32 ppm for 32 control individuals, 1.72 ppm for 24 workers exposed to PCP and other wood preservative chemicals, and 3.78 ppm for 22 workers exposed to PCP as the sole preservative chemical. Age-standardized prevalence rates were significantly higher among the PCP-exposed than among the controls for low-grade infections or inflammations of the skin and subcutaneous tissue, protective membrane of the eyes and the mucosa membrane of the upper respiratory tract. Strong to moderate statistical associations were observed between PCP exposure and increased occurrence of bands (immature leucocytes) and basophils, increased plasma cholinesterase, alkaline phosphatase, gamma globulin and uric acid, and decreased serum calcium. Despite these statistical associations, laboratory values considered to be clinically abnormal were few and not significantly greater in occurrence among the PCP-exposed individuals.

Adult↗

Differences between freshwater and seawater killifish (Oryzias latipes) in the accumulation and elimination of pentachlorophenol.

Freshwater and seawater acclimated (FWA and SWA) killifish (Oryzias latipes) were exposed to pentachlorophenol (PCP) for 3-10 days. Uptake and clearance rates of FWA and SWA killifish were determined. The estimated bioaccumulation factors (BCF) of PCP for FWA and SWA killifish were 1680 and 370, respectively. The smaller uptake rate and faster clearance rate resulted in the lower BCF for SWA killifish. Fresh- and seawater killifish excreted the PCP metabolites, the glucuronide and sulfate conjugates of PCP; the major metabolite of freshwater killifish was PCP sulfate; for seawater acclimated fish, it was PCP glucuronide. The greater excretion of PCP glucuronide by seawater killifish may be responsible for the rapid elimination of PCP. PCP accumulation in killifish decreased with higher pH levels in both freshwater and seawater environments, but these differences were less than the effect of salinity. The results indicate that salinity can affect the accumulation and elimination of environmental pollutants in killifish.

Animals↗

Synergism, antagonism, and additivity of phenol, pentachlorophenol, and dinitrophenol to a fish (Notopterus notopterus).

The toxicity of phenol (P), pentachlorophenol (PCP), and dinitrophenol (DNP) was determined separately and in different combinations with a test fish, Notopterus notopterus, using the procedure of Schubert et al. (1978) that provided a simple, sensitive, and quantitative index of synergism, antagonism and additivity. The combination (P + DNP)/PCP was found to be the most synergistic, while (PCP + DNP)/P was antagonistic in nature. The (DNP + P)/PCP combination was additive in its effect. The other combinations were also synergistic, but to a lesser extent than the (P + DNP)/PCP combination.

Animals↗

Effects of pentachlorophenol and other chemical preservatives on the health of wood-treating workers in Hawaii.

The morbidity and mortality of workers occupationally exposed to wood treating chemicals used in Hawaii for the years 1960 to 1981 were evaluated. The specific chemical exposures investigated were CCA (chromated copper-arsenate), TBTO (tributyl tin oxide) and PCP (pentachlorophenol). Results of detailed medical histories, laboratory and physiological tests, and physical examinations of 88 wood treaters were compared with those of 58 matched controls. The occupationally exposed cases had a significantly higher mean level of urinary PCP as compared to the controls (mean of 174 ppb vs. 35 ppb, micrograms/kg). There were no significant differences between the groups for the other urinary pesticide residues. The medical histories and physical examinations revealed no significant variations between the wood treaters and the comparison group. Review of all organ systems and laboratory data showed no clinically significant differences between exposed and nonexposed cohorts, although elevated hepatic enzymes in both groups merit further study. The results indicated no adverse health effects or increased incidence of mortality resulting from exposure to wood preservative chemicals in wood treaters who had worked in the industry for 0.33 to 26.3 years with a median of 6.5 years. Only 6 deaths were reported, 5 of cardiovascular disease, one of cause undetermined and none of cancer. Total number of deaths were less than the 8 anticipated for this age group.

Animals↗

Effects of pentachlorophenol-contaminated food organisms on toxicity and bioaccumulation in the frog Xenopus laevis.

Sub-adult African clawed frogs (Xenopus laevis) were fed pentachlorophenol (PCP)-injected mealworms containing 64.8 to 2604 ug of PCP per gram of worm for 27 days. There was no mortality and no significant bioaccumulation of PCP in the frogs. After three weeks, frogs fed 2,604 micrograms/g of PCP ceased eating. The no observed adverse effects level (NOAEL) based on significantly reduced food consumption (PCP-injected mealworms) was 638 micrograms/g. This corresponded to a NOAEL based on PCP intake of about 8 micrograms PCP/g frog/day. A toxicity threshold model estimated that about 800 micrograms/L of waterborne PCP may be a threshold for adverse effects in Xenopus or similar amphibians. Further study is needed to verify threshold estimates.

Animals↗