Pentachlorophenol (PCP)


Pentachlorophenol is an organochlorine compound used as a pesticide and a disinfectant. First produced in the 1930s, it is marketed under many trade names. It can be found as pure PCP, or as the sodium salt of PCP, the latter which dissolves easily in water. It can be biodegraded by some bacteria, including Sphingobium chlorophenolicum.
Their use is in decline, and they have been abandoned from most other applications, such as indoor disinfectant, leather and textile application, and herbicide uses. In several countries, their use has been totally discontinued (e.g. Sweden, Germany, Finland) or practically abandoned as a result of severe restrictions (e.g. Denmark). However, PCP is still an important pesticide in some developing countries because of its low cost and broad spectrum. In some developed countries (e.g. France, USA), several thousand tonnes are produced annually. Even in those countries where PCP use has been abandoned, PCP continues to be an important environmental contaminant, because it is imported via various materials treated with it.

Environmental Fate
PCP and other chlorophenols can be metabolized by numerous aquatic and soil microorganisms, but environmental conditions are usually unfavourable for biodegradation. Slow elimination in surface waters, high persistence in sediments, formation of stable metabolites, and the limited adaptation of microorganisms to chlorophenols owing to their high microbial toxicity imply that chlorophenols are practically non-biodegradable in the aquatic environment. In addition, the trace contaminants, especially PCDDs and PCDFs, are not metabolized. Chlorophenols are relatively water soluble in the anionic form. At pH 6.7, 99% of PCP is ionized and in easily leachable form. Therefore, soil contamination may lead to the contamination of groundwater as well. The solubility of the dioxin/furan contaminants is very low (in the order of 10-8 g/litre), and these contaminants are readily sorbed onto soil particles and other surfaces; hence, the risk of contamination of finished drinking-water is not great. In surface waters, organic or clay particles easily transport dioxins/furans to distant sites from their origin. PCP is accumulated by aquatic organisms through uptake from the surrounding water or along the food-chain.

Environmental Levels and Human Exposure:

Air
Because of its high vapour pressure, PCP easily evaporates from treated wood surfaces, and the loss may be as high as 30–80% a year. Its indoor use in buildings is highly inadvisable and has caused a number of poisonings. Volatilization from water is pH dependent, and only the un-ionized form seems to be volatile. Although PCP is ubiquitous, there is little information on its concentrations in ambient air.

Water
In the past, PCP concentrations as high as 25 000–150 000 µg/litre in industrial effluent were reported; at one time, 30–40 t were calculated to be transported by the Rhine per year. Concentrations up to 10500 µg/litre have been reported locally in a river, but concentrations in water samples are usually below 10 µg/litre. Monitoring data showed that PCP concentrations generally decreased (from 0.07–0.14 µg/litre in 1988 to 0.01–0.02 µg/litre in 1993) in the River Elbe after PCP production was stopped in Germany in 1986 and its use was banned in 1989. Such a trend was not seen in the Rhine and its tributaries, where concentrations were even higher in 1990–1991 than in 1980–1989 (maximum levels up to 0.23 µg/litre); the cause is not known (UBA, 1996), but it indicates continuing environmental contamination. Under special conditions, PCP may accumulate to very high concentrations in groundwater. In the spring water of a Finnish village, concentrations of 70–140 µg/litre were found, and investigation of the groundwater reservoir revealed extremely high concentrations of 56 000– 190 000 µg/litre in the deep parts of the reservoir. The obvious source was a local sawmill using chlorophenols since 1940s. PCP concentrations in drinking-water are usually in the range of 0.01–0.1 µg/litre. It has been thought that PCP's odour threshold is low and should render water unpalatable, but a recent episode in Finland demonstrated that people may drink water containing upto 100 µg/litre of chlorophenols with few complaints. As stated above, evaporation depends on pH and temperature, and detection in cold water is unreliable.

Food
In Canada, analysis of 881 pork liver tissue samples revealed a gradual decline in PCP levels in 1988–1989 from those in earlier years. Some 6.6% of the samples contained levels in excess of 0.1 mg/kg, the highest level being 0.72 mg/kg. Of 51 beef liver samples, 2.0% had levels in excess of 0.1 mg/kg, the maximum level being 0.35 mg/kg. Examination of 214 chicken and 68 turkey liver samples showed only one with a level above 0.1 mg/kg; this incident was traced to the use of wood shavings as bedding. Another study in Slovakia found detectable PCP concentrations in 79% of food samples from school kitchens; the average PCP concentration in positive samples was 6.3 µg/kg.

Kinetics and Matabolism in Laboratory Animals and Humans
The kinetics of PCPs have been reviewed on a number of, and only a general overview and a few recently emphasized points are presented here. PCP is probably well absorbed orally although bioavailability may be influenced by food. During occupational exposure, PCP is well absorbed via the dermal and pulmonary routes. Good oral and dermal absorption is supported by animal studies. It is likely that most PCP is conjugated to glucuronic acid and excreted into urine, although the rate of glucuronidation has been controversial. It is somewhat debatable whether an important rodent metabolite, tetrachloro-1,4-hydroquinone, is formed in humans, but at most it is a minor metabolite. PCP is avidly bound (99.5%) to plasma proteins in humans. There is some uncertainty as to the elimination rate of PCP, and half-lives from 33 hours to 16 days have been reported. Both protein binding and urinary pH could cause variation, but there may also be methodological reasons for the differences found. One may safely assume that the half-life is a few days. The bioconcentration factor for PCP is rather low, and steady-state levels in human adipose tissue amount to only 2–4 times the average daily intake.

Effects on Humans
The paramount difficulty in interpreting human studies, especially long-term studies, has been simultaneous exposure to other chemicals. Those working in chemical industries are often simultaneously exposed to chlorophenols, solvents, dibenzodioxins, dibenzofurans, and the chemical being synthesized. Those working in forestry or agriculture are often simultaneously exposed to chlorophenols, chlorophenoxy acids, dibenzodioxins and dibenzofurans, as well as other pesticides. Owing to the extreme toxicity and high carcinogenic potency of TCDD in laboratory animals, there has been a tendency to attribute most of the toxicity to dioxins and furans. However, as dioxins and furans exist only as impurities, any exposure to them means perhaps close to a million-fold higher exposure to the main chemical. An exception is early years of 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) production, which caused remarkably high TCDD exposure. In addition, the vapour pressure and water solubility of chlorophenols are substantially higher than those of dioxins and furans, favouring higher exposure via air and water. Also, absorption of chlorophenols through skin is probably better than that of dioxins. Therefore, the primary relevance of the measured concentrations of kinetically persistent dioxins/furans may be that they indicate past exposure to the main chemical, especially if the exposure is long-lasting. The slow pattern of the kinetics of dioxins and furans dictates that, for their own toxicity, a steady gradual exposure is more important than an occasional short exposure, unless this is very large. In fact, the long half-life of dioxins (5–10 years or more) means that a steady-state level will be achieved only in 30–40 years at a constant intake. This renders it unlikely that an occasional exposure, such as in forestry and agriculture, would significantly change the body balance, even if the concentrations of the main chemical increase dramatically during spraying or handling. The situation is quite different in chemical industries. If the workers are exposed continuously for years or decades, then extremely high dioxin levels (thousands of pg/g fat) may be accumulated.

PCP Poisoning
PCP and other higher chlorinated phenols act cellularly to uncouple oxidative phosphorylation and to inhibit ATPase and several other enzymes. This leads to excessive heat production and fever. Symptoms of acute poisoning include central nervous system disorders, dyspnoea, and hyperpyrexia, leading to cardiac arrest. Marked rigor mortis is typical. In general, acute human poisoning is seen only after large accidental or suicidal doses. The estimated minimal lethal dose in humans has been calculated to be 29 mg/kg of body weight. In addition to metabolic, respiratory, and central nervous system effects seen only 7 after an acute large oral dose, they classified the clinical features as effects on skin and haematopoietic tissue, renal effects, and gastrointestinal effects. Some of these effects, notably chloracne, are probably due to dioxin/furan impurities. These effects have occasionally been seen after heavy occupational exposure. In a Chinese PCP production plant, high prevalence of chloracne, increased urinary porphyrin excretion, and decreased motor nerve conduction velocities were observed in the high-exposure area. These are likely due to dioxin-like impurities. Drinking-water exposure was associated with gastrointestinal symptoms (nausea, pains, diarrhoea) and mild skin disorders (itching, eczema). The latter findings can be assumed to be due to chlorophenols, as no dioxin exposure was noted.

References
http://www.who.int/water_sanitation_health/dwq/chemicals/pentachlorophenol.pdf

Recent Publications
Toxicological Profile of Chlorophenols and Their Derivatives in the Environment: The Public Health Perspective
The Pentachlorophenol Metabolite Tetrachlorohydroquinone Induces Massive ROS and Prolonged p-ERK Expression in Splenocytes, Leading to Inhibition of Apoptosis and Necrotic Cell Death
The pentachlorophenol-dehalogenating Desulfitobacterium hafniensestrain PCP-1