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Pentachlorophenol

1. NAME
   1.1 Substance
   1.2 Group
   1.3 Synonyms
   1.4 Identification numbers
      1.4.1 CAS number
      1.4.2 Other numbers
   1.5 Main brand names, main trade names
   1.6 Main manufacturers, main importers
2. SUMMARY
   2.1 Main risks and target organs
   2.2 Summary of clinical effects
   2.3 Diagnosis
   2.4 First-aid measures and management principles
3. PHYSICO-CHEMICAL PROPERTIES
   3.1 Origin of the substance
   3.2 Chemical structure
   3.3 Physical properties
      3.3.1 Colour
      3.3.2 State/Form
      3.3.3 Description
   3.4 Hazardous characteristics
4. USES
   4.1 Uses
      4.1.1 Uses
      4.1.2 Description
   4.2 High risk circumstance of poisoning
   4.3 Occupationally exposed populations
5. ROUTES OF EXPOSURE
   5.1 Oral
   5.2 Inhalation
   5.3 Dermal
   5.4 Eye
   5.5 Parenteral
   5.6 Other
6. KINETICS
   6.1 Absorption by route of exposure
   6.2 Distribution by route of exposure
   6.3 Biological half-life by route of exposure
   6.4 Metabolism
   6.5 Elimination and excretion
7. TOXICOLOGY
   7.1 Mode of Action
   7.2 Toxicity
      7.2.1 Human data
         7.2.1.1 Adults
         7.2.1.2 Children
      7.2.2 Relevant animal data
      7.2.3 Relevant in vitro data
      7.2.4 Workplace standards
      7.2.5 Acceptable daily intake (ADI)
   7.3 Carcinogenicity
   7.4 Teratogenicity
   7.5 Mutagenicity
   7.6 Interactions
8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS
   8.1 Material sampling plan
      8.1.1 Sampling and specimen collection
         8.1.1.1 Toxicological analyses
         8.1.1.2 Biomedical analyses
         8.1.1.3 Arterial blood gas analysis
         8.1.1.4 Haematological analyses
         8.1.1.5 Other (unspecified) analyses
      8.1.2 Storage of laboratory samples and specimens
         8.1.2.1 Toxicological analyses
         8.1.2.2 Biomedical analyses
         8.1.2.3 Arterial blood gas analysis
         8.1.2.4 Haematological analyses
         8.1.2.5 Other (unspecified) analyses
      8.1.3 Transport of laboratory samples and specimens
         8.1.3.1 Toxicological analyses
         8.1.3.2 Biomedical analyses
         8.1.3.3 Arterial blood gas analysis
         8.1.3.4 Haematological analyses
         8.1.3.5 Other (unspecified) analyses
   8.2 Toxicological Analyses and Their Interpretation
      8.2.1 Tests on toxic ingredient(s) of material
         8.2.1.1 Simple Qualitative Test(s)
         8.2.1.2 Advanced Qualitative Confirmation Test(s)
         8.2.1.3 Simple Quantitative Method(s)
         8.2.1.4 Advanced Quantitative Method(s)
      8.2.2 Tests for biological specimens
         8.2.2.1 Simple Qualitative Test(s)
         8.2.2.2 Advanced Qualitative Confirmation Test(s)
         8.2.2.3 Simple Quantitative Method(s)
         8.2.2.4 Advanced Quantitative Method(s)
         8.2.2.5 Other Dedicated Method(s)
      8.2.3 Interpretation of toxicological analyses
   8.3 Biomedical investigations and their interpretation
      8.3.1 Biochemical analysis
         8.3.1.1 Blood, plasma or serum
         8.3.1.2 Urine
         8.3.1.3 Other fluids
      8.3.2 Arterial blood gas analyses
      8.3.3 Haematological analyses
      8.3.4 Interpretation of biomedical investigations
   8.4 Other biomedical (diagnostic) investigations and their interpretation
   8.5 Overall Interpretation of all toxicological analyses and toxicological investigations
   8.6 References
9. CLINICAL EFFECTS
   9.1 Acute poisoning
      9.1.1 Ingestion
      9.1.2 Inhalation
      9.1.3 Skin exposure
      9.1.4 Eye contact
      9.1.5 Parenteral exposure
      9.1.6 Other
   9.2 Chronic poisoning
      9.2.1 Ingestion
      9.2.2 Inhalation
      9.2.3 Skin exposure
      9.2.4 Eye contact
      9.2.5 Parenteral exposure
      9.2.6 Other
   9.3 Course, prognosis, cause of death
   9.4 Systematic description of clinical effects
      9.4.1 Cardiovascular
      9.4.2 Respiratory
      9.4.3 Neurological
         9.4.3.1 Central nervous system (CNS)
         9.4.3.2 Peripheral nervous system
         9.4.3.3 Autonomic nervous system
         9.4.3.4 Skeletal and smooth muscle
      9.4.4 Gastrointestinal
      9.4.5 Hepatic
      9.4.6 Urinary
         9.4.6.1 Renal
         9.4.6.2 Others
      9.4.7 Endocrine and reproductive systems
      9.4.8 Dermatological
      9.4.9 Eye, ears, nose, throat: local effects
      9.4.10 Haematological
      9.4.11 Immunological
      9.4.12 Metabolic
         9.4.12.1 Acid-base disturbances
         9.4.12.2 Fluid and electrolyte disturbances
         9.4.12.3 Others
      9.4.13 Allergic reactions
      9.4.14 Other clinical effects
      9.4.15 Special risks
   9.5 Other
   9.6 Summary
10. MANAGEMENT
   10.1 General principles
   10.2 Life supportive procedures and symptomatic treatment
   10.3 Decontamination
   10.4 Enhanced elimination
   10.5 Antidote treatment
      10.5.1 Adults
      10.5.2 Children
   10.6 Management discussion
11. ILLUSTRATIVE CASES
   11.1 Case reports from literature
12. ADDITIONAL INFORMATION
   12.1 Specific preventive measures
   12.2 Other
13. REFERENCES
14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE ADDRESS(ES)
    PENTACHLOROPHENOL (PCP)

    International Programme on Chemical Safety
    Poisons Information Monograph 405
    Chemical

    1.  NAME

        1.1  Substance

             Pentachlorophenol

        1.2  Group

             Phenol

        1.3  Synonyms

             2,3,4,5,6-pentachlorophenol,
             Chlorophen,
             PCP,
             Penchlorol,
             Penta,
             Pentachlorofenol,
             Pentachlorofenolo,
             Pentachlorphenol,
             Pentaclorofenol,
             Pentanol,

        1.4  Identification numbers

             1.4.1  CAS number

                    87-86-5 (Sodium pentachlorophenate)

             1.4.2  Other numbers

                    UN number: 2020

        1.5  Main brand names, main trade names

             Acutox; Chen-pentas; Chem-Tol; Cryptogil ol; Dowicide 7;
             Dowicide EC-7; Dow Pentachlorophenol DP-2 Antimicrobial;
             Durotox; EP 30; Fingifen; Fongol; Glazd Penta; Grundier
             Arbezol; Jimo-Cupim; Lauxtol; Lauxtol A; Liroprem; Moosuran;
             NCI-C 54933; NCI-C 55378; Pentacon; Panta-Kil; Pentasol;
             Penta-Kill; Penwar; Peratox; Permacide; Permagad; Permasan;
             Permatox; Priltox; Permite; Santopen; Satophen 20; Sinituho;
             Term-i-trol; Thompson's Wood Fix; Weedone; Withophen P;
             Withophen N.

        1.6  Main manufacturers, main importers

             To be completed by each centre.

    2.  SUMMARY

        2.1  Main risks and target organs

             The main risks in acute poisoning are: hyperpyrexia,
             tachycardia, and a rise in the metabolic rate leading to
             death by cardiac arrest.  In chronic exposure, the main risks
             are:  skin, blood, neurological and respiratory disorders,
             porphyria, non-specific symptoms, and the possibility of
             cancer.
    
             Target organs are:  skin, respiratory system, central nervous
             system (CNS), liver and kidneys, but especially metabolism at
             the cellular level.

        2.2  Summary of clinical effects

             Symptoms of acute systemic poisoning are:  headache,
             profuse sweating, depression, nausea, weakness, and sometimes
             fever; tachycardia, tachypnea, pain in the chest, thirst. 
             Abdominal colic is frequent.
    
             Mental distress can occur, progressing to coma and
             occasionally convulsions; irritation of the skin, mucous
             membranes, and respiratory tract (including painful
             irritation of the nose and intense sneezing when
             pentachlorophenol is inhaled); contact dermatitis and
             chloracne.
    
             Chronic exposure can cause: porphyria cutanea tarda, weight
             loss, increased basal metabolic rate, functional changes of
             the liver and kidneys.  Insomnia and vertigo have also been
             reported.

        2.3  Diagnosis

             Symptoms of acute poisoning include abdominal pain,
             headache, profuse sweating, depression, nausea, weakness.
             Less commonly, fever; tachycardia, tachypnea, chest pain and
             thirst occur. Symptoms may progress to coma and occasionally
             convulsions.
    
             Other effects include irritation of the skin, mucous
             membranes, and respiratory tract (including painful
             irritation of the nose and intense sneezing after
             inhalation); contact dermatitis and chloracne.
    

             Routine blood biomedical analysis, especially electrolytes,
             acid-base balance; hepatic enzymes; creatinine and BUN; blood
             elements.
    
             Toxicity occurs above 1 mg/l and symptoms become obvious at
             approximately 40 mg/l.
    
             Urine: urine analysis (strict measurement of kidney
             function); porphyrines, delta-aminolevulinic acid. Toxicity
             is evident at urinary concentrations of 1 mg/l or more.

        2.4  First-aid measures and management principles

             Remove the patient from exposure.
    
             Admit the patient to hospital (decontaminate patient before
             admission, if possible).
    
             Decontaminate eyes with large amounts of water.
    
             If patient is alert or has a coughing reflex:
    
             Perform gastric lavage with water or saline isotonic solution
             or 5% sodium bicarbonate using a cuffed endotracheal tube.
             However, caution is needed since the solvents of PCP products
             are usually petroleum distillates.
    
             Give activated charcoal, 30 to 50 g in 200 ml water.
    
             Control fever by physical means: sponge or tepid bathing or
             covering the patient with low-temperature blankets.Aspirin or
             other antipyretics are likely to enhance the toxicity of
             phenolic compounds.
    
             If the patient is unconscious:
    
             Provide a clear airway and respiratory assistance.
    
             Treat symptomatically.  Maintain blood pressure.
    
             Give intravenous fluids (watch for cerebral oedema).
    
             Give diazepam intravenously to control convulsions.
    
             Haemodialysis and haemoperfusion may be considered.
    
             No specific antidote is known.

    3.  PHYSICO-CHEMICAL PROPERTIES

        3.1  Origin of the substance

             Synthetic
    
             PCP is produced by two methods: direct chlorination of
             phenol; and hydrolysis of hexachlorbenzene.
    
             Direct chlorination is performed in two steps: liquid phenol,
             chlorophenol, or polychlorophenol is bubbled with chlorine
             gas at 30-40C, to produce 2,4,6-trichlorophenol, which is
             then converted to PCP by further chlorination at a higher
             temperature in the presence of catalysts (aluminium, antimony
             and their chlorides). The second method involves alkaline
             hydrolysis of hexachlorobenzene (HCB) in methanol and
             dihydric alcohols, water, and solvents at 130-170C. 
             Numerous by-products are created, in addition to PCP.
    
             Toxic by-products are chlorinated esters, dibenzofurans, and
             di-benzo-p-dioxines; HCB is also produced by the second
             method (WHO, 1987).

        3.2  Chemical structure

             Formula:  CHC10 C1 C16 5 C1 OH C1 C1
    
             Molecular weight: 266.3
    
             Note: The sodium salt (Na-pentachlorophenate) has a different
             formula and solubility, but the toxic effects are the
             same.

        3.3  Physical properties

             3.3.1  Colour

             3.3.2  State/Form

             3.3.3  Description

                    Boiling point: 309-310 C (decomposition at 754 mm)
    
                    Melting point: 191 C
    
                    Density (g/ml):1.987
    
                    Vapour pressure kPa (mmHg at 20 C)2  10-6
                    (1.5  10-5)
    
                    Saturation vapour density: 250 mg/m3 (20 C)
    

                    Steam volatility: 0.167 (g/100 g water vapour at
                    100C)
    
                    Solubility in fat g/kg 213(37 C):
    
                    n-Octanol-water partition coefficient (log P)
                    4.84 pH 1.2 3.56 pH 6.5 3.32 pH 7.2 3.86 pH 13.5 pK
                    (25 C):4.7
    
                    Solubility in water:
    
                    (g/100 ml at 20 C) 0.014pH=5 2pH=7 8pH=8 1pH=15
    
                    Solubility in organic acetone 50 solvents (g/100 g
                    atbenzene 15 25C) ethanol 95% 120 ethylene glycol 11
                    isopropanol 85 methanol 180

        3.4  Hazardous characteristics

             Pure pentachlorophenol consists of light tan to white,
             needle-like crystals.
    
             It has a pungent odour when heated.
    
             Its vapour pressure indicates that it is relatively volatile
             even at ambient temperature.
    
             The substance decomposes on heating in the presence of water,
             forming corrosive fumes (hydrochloric acid).
    
             Pentachlorophenol is non-flammable and non-corrosive in its
             unmixed state, whereas its solution in oil causes rubber to
             deteriorate.
    
             Formulated products may be flammable.
    
             Due to nucleophilic reactions of the hydroxyl group,
             pentachlorophenol can form esters with organic and inorganic
             acids and ethers with alkylating agents such as methyl iodide
             and diazomethane.
    
             Due to electron withdrawal by chlorine atoms in the benzene
             ring, pentachlorophenol behaves as an acid, yielding
             water-soluble salts such as sodium pentachlorophenate. 
             Pentachlorophenol occurs in two forms: the anionic phenolate
             at neutral to alkaline pH; and the undissociated phenol at
             acidic pH.
    
             Odour threshold (mg/l) 1.6 (in water).
    
             Olfactory threshold (mg/l)  0.03 (in water).
    

             Technical grade pentachlorophenol contains many impurities,
             depending on the manufacturing method used.  These impurities
             consist of other chlorophenols and several microcontaminants,
             mainly polychlorodibenzodioxins (PCDDs),
             polychlorodibenzofurans (PCDFs), and polychlorinated
             biphenyls (PCBs).
    
             Since the toxicity of PCDDs and PCDFs mostly depends not only
             on the number but also on the position of chlorine
             substituents, an accurate characterization of PCP impurities
             is needed.  The highly toxic
             2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has only been
             confirmed once in commercial PCP samples.  The higher PCDDs
             and PCDFs are more characteristic of PCP formulations.
    
             Hexachlorodibenzo-p-dioxin (H6CDD), which is also considered
             highly toxic and carcinogenic, and octachlorodibenzo-p-dioxin
             (CDD), are present in relatively high amounts in unpurified
             technical grade PCP.  Hexachlorobenzene is also found at
             levels of 400 mg/kg in commercial grade PCP.
    
             The comparative toxicity of technical versus pure PCVP needs
             to be clearly established.  There is a need for specification
             of a technical PCP (WHO, 1987).
    
             Chemical activity and reactivity:
    
             Pentachlorophenol forms salts with alkaline metals; sodium
             pentachlorophate is converted exothermically to
             octachlorodibenzo-para-dioxin at 360C; heating of the sodium
             salt to 280C produces 0.9 mg/kg
             octa-chlorodibenzo-para-dioxins and 0.3 mg/kg
             hepta-chlorodibenzo-para-dioxins, together with 0.02 to 0.03
             mg/kg hexa-, penta-, and
             tetra-chlorodibenzo-para-dioxins.
    
             Volatilization can be an important source of PCP from water
             and soil surfaces as well as from PCP treated materials.  The
             pH seems to be the major factor that controls the extent of
             PCP absorption: absorption is maximal in strongly acidic
             soils.
    
             Leaching of PCP occurs more easily in alkaline soils than in
             acidic soils. PCP is subject to abiotic (photochemical)
             degradation in water, organic solvents, and on solid
             surfaces.
    
             There are many fungi and bacteria that attack PCP and cause
             biotic degradation in water and soil.

    4.  USES

        4.1  Uses

             4.1.1  Uses

             4.1.2  Description

                    The main advantages of PCP and its salts are
                    that they are very effective biocides that have a
                    broad application and are inexpensive.
    
                    PCP and its derivatives have a variety of applications
                    in agriculture, industry, and domestic fields.
    
                    Their major application is wood preservation,
                    particularly on a commercial scale.  They protect
                    construction lumber, and also poles and posts, from
                    fungal rots and decay.  They also prevent
                    staining.
    
                    PCP is also used as a herbicide, defoliant, fungicide,
                    pre-harvest dessicant, bactericide, insecticide, and
                    molluscicide and to control termites.
    
                    PCP has many registered industrial uses.  It is used
                    in construction of boats and buildings, to control
                    mould in petroleum drilling and production, and in the
                    treatment of cable coverings, canvas belting, nets,
                    and construction lumber and poles.  It is used in
                    paints, pulp stock, pulp, and paper, and to cool tower
                    water, and as preservative for hard board and particle
                    board.
    
                    Because of increased concern about the potential
                    health hazard from PCP and its impurities, the pattern
                    of use has changed in the last few years.
    
                    PCP is used in the home, both indoors and outdoors,
                    mostly to treat wood.  It is the main active
                    ingredient in certain wood preservatives used in the
                    home, and is added to products such as stains and
                    paints.  Cases of apparent PCP intoxications after
                    indoor application in homes have been reported.  (Its
                    indoor use is forbidden in some countries, e.g., the
                    Netherlands).
    
                    Other applications of PCP include health-care products
                    and disinfectants for the home, farms, and hospital. 
                    PCP may also be contained in dental- and skin-care
                    products, bacterial soaps, and laundry products.
                    

        4.2  High risk circumstance of poisoning

             Occupational exposure (most cases): PCP is used to
             protect wood and in other cellulose products (see section
             4.3).
    
             Accidental exposure to PCP as a result of its application in
             the interior of homes or in PCP-treated wood houses.
    
             PCP-contaminated food or water, and improper laundering of
             diapers and bedding with soap that contains
             pentachlorophenate.
    
             Suicide attempts with PCP.
    
             In fires, the thermal decomposition of PCP or NaPCP may yield
             significant amounts of polychlorinated dibenzo-dioxines
             (PCDD) and dibenzofurans (PCSF) (WHO, 1987).

        4.3  Occupationally exposed populations

             Workers involved in:
    
             Manufacture, packaging, labelling, storage, and shipping of
             PCP.
    
             Application of PCP to wood (wood-immersion, painting).
    
             Sawmills.
    
             Carpentry and other timber and wood-working.
    
             Knapsack sprayers (e.g., termite control, agricultural
             pesticides).
    
             Greenhouses.
    
             Walking with bare feet through areas where PCP was
             sprayed.
    
             Addition of PCP to cellulose products, such as starches and
             adhesives.
    
             Addition of PCP to leather, oils, paints, latex, and
             rubber.
    
             Manufacture of herbicides.
    
             Industrial cooling towers and evaporative condensers.
    
             Treatment and handling of wood, burlap, canvas, rope,
             leather, and manufacture of paper.
    

             Petroleum and other drilling.
    
             Manufacture and use of paints and adhesives.
    
             Telephone and electrical line work.
    
             Dyeing and cleaning of garments.

    5.  ROUTES OF EXPOSURE

        5.1  Oral

             PCP is readily absorbed by the gastrointestinal tract
             and reaches peak plasma levels in 4 h.  Absorption is faster
             when PCP is dissolved in alcohol (WHO, 1987).
    
             Measurements of PCP in the air, water, food, drugs, and
             consumer products confirm that nearly every environmental
             area is contaminated with low levels of PCP.
    
             For workers using PCP, the major routes of absorption are
             dermal and inhalation.

        5.2  Inhalation

             Inhalation is one of the two major routes of absorption
             in the workplace.  (Dermal absorption is the other major
             route).
    
             Although no experimental data are available on absorption by
             inhalation, the cases of acute intoxication reported are
             almost exclusively due to inhalation and dermal contact with
             high doses of PCP (WHO, 1987).
    
             Fine dusts and sprays of PCP or chlorophenate cause painful
             irritation to the upper respiratory tract and eyes.  This
             intense pain is an excellent warning sign.  If it affects the
             nose, it will alert the person to avoid further exposure
             which might produce adverse systemic effects.  Workers
             exposed to concentrations of 1 mg/m3 or more have reported
             painful nasal irritation.

        5.3  Dermal

             Dermal absorption is the major route of absorption in
             the workplace. (Inhalation is the other major route).  PCP is
             readily absorbed through the skin.
    
             A case of skin absorption was reported where a high PCP level
             in the urine was found after a worker had cleaned a
             paintbrush for only 10 min in a can that contained a 4%
             solution of PCP (Benvenue et al 1967).  Workers handling

             PCP-treated lumber absorb from one-half to two-thirds of the
             total PCP accumulation through the skin.
    
             These exposures result in low quantities of PCP in the serum
             and urine of occupationally exposed persons.  Improvements in
             industrial hygiene can reduce PCP concentrations in the
             urine.

        5.4  Eye

             PCP causes painful irritation of the eyes.  No data are
             available on the importance of the eyes as a route of
             entry.

        5.5  Parenteral

             The subcutaneous or intraperitoneal injection of C14-PCP
             has been used in autoradiographic studies of PCP distribution
             in animals (WHO, 1987).

        5.6  Other

             No data are available.

    6.  KINETICS

        6.1  Absorption by route of exposure

             PCP is efficiently absorbed through the skin, the lungs,
             and the gastrointestinal tract.
    
             In human volunteers, the observed half-life for absorption
             was about 1.3 h and the peak plasma level occurred 4 h after
             ingestion.  Absorption was enhanced when PCP was dissolved in
             alcohol (WHO, 1987).
    
             For the general population, the uptake of PCP by the oral
             route is the most important.  In the workplace, or in
             PCP-treated dwellings, the major routes of absorption are
             probably the dermal and inhalation routes (WHO, 1987).

        6.2  Distribution by route of exposure

             Usually, the highest PCP levels can be found in the
             urine immediately after exposure.  Consequently, the PCP
             concentrations in the tissues account for only a small
             fraction of the PCP dose.
    
             Experimental studies do not show a uniform distribution
             pattern of PCP, but indicate that very high levels can be
             found in the liver and kidneys.  After chronic exposure, most
             PCP is absorbed by the central nervous system. In rats, the
             amount of PCP that crosses the placenta is very low.
    

             There is an indication that, due to enterohepatic
             circulation, conjugated PCP is transferred to the gall
             bladder and bile.
    
             Autopsies performed in people who have died from PCP
             intoxication show that PCP levels in the liver, kidneys, and
             lungs are often elevated.  The high levels in the lungs might
             be caused by uptake of PCP by inhalation.  In general, PCP
             levels in various tissues do not clearly indicate
             accumulation of PCP, because PCP levels in the blood are
             often similar to the levels in the tissues (WHO, 1987).

        6.3  Biological half-life by route of exposure

             PCP is readily absorbed through the skin as well as
             through the respiratory and gastrointestinal tracts.  In
             animals, the half-life for oral absorption varies from 1.8 to
             3.6 h in monkeys to 0.36 to 0.46 h in rats.
    
             In human volunteers, the observed half-life for oral
             absorption is about 1.3 h (WHO, 1987).
    
             Estimates of the elimination half-life vary. One study found
             the half-life of PCP in plasma was about 30 h, while that for
             PCP and PCP glucuronide elimination in the urine was 33 and
             13 h, respectively (WHO, 1987).
    
             In a further study, an elimination half-life of 17 days was
             calculated from measuring PCP in both urine and blood (Uhl et
             al 1986).

        6.4  Metabolism

             In animals,  PCP is excreted unchanged and as
             metabolites which include tetrachlorhydroquinone and
             glucuronides.  In man, PCP is eliminated both unchanged and
             as the glucuronide.  In one study, tetrachlorhydroquinone was
             found in the urine of two spray-men who were occupationally
             exposed. This metabolic transformation was confirmed in liver
             homogenates in humans and rats (WHO, 1987).

        6.5  Elimination and excretion

             PCP is rapidly eliminated by most animals. It is cleared
             from the plasma by distribution to the tissues and by
             excretion via the urine and the faeces; the metabolites, when
             produced, are also excreted rapidly.
    
             The PCP concentration in human urine has been widely used as
             an indicator of the PCP body burden, based on the fact that,
             in man, renal excretion of PCP is the major elimination
             route.  Volunteers excreted 74% of the total dose in urine as
             PCP, and 12% as PCP glucuronide.  About 4% of the total dose

             was eliminated in the faeces.  In samples taken from
             non-occupationally exposed people, two-thirds of the PCP
             detected in the urine was conjugated.
    
             Ninety-nine per cent of PCP in rat plasma is bound to
             protein. Human plasma has high binding capacity (96%) that
             could explain the long retention times in humans.  After a
             single oral dose was given to volunteers, the maximum urinary
             excretion was reached 40 h after ingestion and 37 h after the
             maximum plasma level of PCP.  This delay is due to a marked
             enterohepatic circulation.  The elimination half-life of PCP
             from plasma was about 30 h, while that for PCP and PCP
             glucuronide elimination in the urine was 33 and 13 h,
             respectively (WHO, 1987).
    
             In a further study, an elimination half-life of 17 days was
             calculated from measuring PCP in both urine and blood (Uhl et
             al 1986).

    7.  TOXICOLOGY

        7.1  Mode of Action

             As with other chlorophenols, the biochemical action of
             pentachlorophenol is active uncoupling of oxidative
             phosphorylation.  The molecular basis for this is not
             clear.
    
             PCP binds to mitochondrial protein and inhibits mitochondrial
             ATP-ase activity.  Thus, both the formation of ATP and the
             release of energy to the cell from the breakdown of ATP to
             ADP are prevented.  Electron transport is not inhibited by
             PCP, although reactions dependent on available high-energy
             bonds, such as oxidative and glycolytic phosphorylation, are
             affected.
    
             Binding to enzymic protein has ben reported and may lead to
             the inhibition of other cellular enzymes.
    
             There is an increase in cellular oxygen demand during the
             uncoupling of oxidative phosphorylation.  This causes the
             initial rise in respiration rate reported in individuals
             poisoned by PCP.
    
             PCP is toxic to the liver, kidneys, and central nervous
             system.
    
             The toxicity of PCP is increased by impurities in some
             formulations. In some instances, it is very difficult to know
             whether the impurities have affected the poisoning. 
             Dermatitis and chloracne are caused by contaminants such as
             PCDDs and PCDFs.

        7.2  Toxicity

             7.2.1  Human data

                    7.2.1.1  Adults

                             In humans, the minimum lethal oral
                             dose (LDLo) has been estimated at 29 mg/kg
                             body weight (Ahlborg and Thunberg, 1980).
    
                             Braun et al (1979) reported the ingestion of
                             0.1 mg/kg PCP by 4 volunteers with no
                             clinical effects.
    
                             It is generally agreed that the symptoms and
                             signs of acute chlorophenol toxicity result
                             from the effects of the chlorophenol molecule
                             itself, rather than from the
                             microcontaminants.  Chlorophenol rapidly
                             causes hyperthermia, profuse sweating and
                             early death.  These signs are not observed in
                             animals exposed only to PCDD and PCDF.
    
                             Blair (1961) reported several deaths.  Levels
                             of PCP were 5.9-6.2 mg/100 g in the liver,
                             and 4.1-8.4 mg/100 g in kidney tissue.  PCP
                             levels in the blood were 5.3-9.6 mg/100 ml
                             and in urine, 2.8 mg/100 ml.
    
                             PCP-contaminated diapers caused 20 cases of
                             intoxication, with two fatalities.  The
                             concentration of PCP in the diapers ranged
                             from 109-172 ppm and serum levels of PCP
                             ranged from 7 to 118 ppm (Armstrong et al
                             1969).
    
                             According to a study of post-mortem samples,
                             PCP was found in urine in concentrations of
                             28-96 ppm (Bevenue and Beckman, 1967). Haley
                             (1977) reported a case of intentional
                             intoxication with PCP.  The serum level of
                             PCP was 150 ppm 5 h after ingestion, and 28
                             ppm 2 weeks later. PCP in the urine showed
                             marked variation during forced diuresis (from
                             2.3 ppm to 8.6 ppm).
    
                             Studies designed to examine biochemical
                             changes in woodworkers exposed to high levels
                             of PCP for extended periods did not show
                             statistically significant organic effects.
                             Chronic exposure leading to blood
                             concentrations as high as 4 ppm is likely to
                             cause borderline effects.
    

                             Several epidemiological studies from Sweden
                             and the United States have associated soft
                             tissue sarcomas with occupational exposure to
                             PCP.  Surveys from Finland and New Zealand
                             havenot confirmed this relationship. There
                             are no conclusive reports of increased
                             incidence of cancer in workers specifically
                             exposed to PCP.

                    7.2.1.2  Children

                             Fatal poisoning of infants was
                             traced to improper laundering of diapers and
                             bedding with material containing
                             Na-pentachlorophenate and other phenols
                             (Armstrong et al, 1969).
    
                             No other data are available.

             7.2.2  Relevant animal data

                    ACUTE TOXICITY (LD50) OF PCP 
    
                    Animal    Sex  Dose     Route    Reference
    
                    Rat       F    210+a    Oral     Deichman et al, 1942
                    Rat       F    66.3     Subcut   Deichman et al. 1942
                    Rat       F    77.9 ++b Oral     Deichman et al. 1942
                    Rat       M    149      Derm     Noakes et al. 1969
                    Rat       M    146 ++   Oral     Gaines, 1969
                    Rat       M    320 ++   Derm     Gaines, 1969
                    Rat            11.7     Inh      Hoben et al. 1976
                    Mouse          130      Oral     Pleskoma et al. 1959
                    Mouse          261      Derm     Pleskoma et al. 1959
                    Mouse          63       Subcut   Pleskoma et al. 1959
                    Mouse          29       Ip       Pleskoma et al. 1959
                    Guinea-pig     100      Oral     Knudsen et al. 1974
                    Sheep          120      Oral     Knudsen et al. 1974
    
                    a +  PCP in aqueous solution
                    b ++ PCP in oil solution
    
                    The no-observed-adverse-effect-levels (NOAELs)
                    determined in rats that were given pure technical and 
                    purified technical grades of PCP orally were about 2 
                    mg/kg per day.

             7.2.3  Relevant in vitro data

                    Not available.

             7.2.4  Workplace standards

                    The TLV-TWA (Threshold Limit Value-Time
                    Weighted Average) of the 1986-1987 ACGIH (American
                    Conference of  Governmental Industrial Hygienists),
                    including the  potential exposure by the cutaneous
                    route, is 0.5 mg/m3.
    
                    Time Weighted Average OSHA 0.5 mg/m3 (skin) 
                    Short-term Exposure Limit ACGIH 1.5 mg/m3
    
                    Maximum Allowable Concentration  (USSR) 0.1 mg/m3

             7.2.5  Acceptable daily intake (ADI)

                    Exposure Limit Values
    
                    Medium Country/Organization Exposure descriptiona
                    Value Limit
    
                    Air Japan  NACO.5 mg/m3
    
                    Workplace Sweden RECL 8 h TWA 0.5 mg/m3 STEL 1.5 mg/m3
    
                    Workplace United Kingdom RECL 8 h TWA 0.5 mg/m3 STEL -
                    10 m TWA 1.5 mg/m3
    
                    Medium Country/Organization Exposure descriptiona 
                    Value Limit
    
                    Workplace Federal Republic of Germany MAC - 8 h TWA
                    0.5 mg/m3
    
                    "USA TLV 0.5 mg/m3 STEL1.5 mg/m3 PEL -TWA 0.5 mg/m3
    
                    "Italy  TLV 0.5 mg/m3
    
                    "USSR MAC ceiling value 0.1 mg/m3
    
                    Ambient air USSR  MAC (1x per day) 0.02 mg/m3 
                    (average per day) 0.005 mg/m3 PSL (1x per day) 0.001
                    mg/m3
    
                    Food USAADI3 mg/kg  body weight/day
    
                    Food plant Federal Republic of Germany MRL 0.01-0.03
                    mg/kg
    
                    Surface water  USSR MAC 0.01 mg/l
    
                    Drinking water WHOMAC (guideline) 10 mg/l
    

                    MAC  = Maximum allowable concentration
                    SREL = Short-term exposure limit
                    PEL  = Permissible exposure limit
                    PSL  = Preliminary safety limits
                    MRL  = Maximum residue limit
                    TWA  = Time-weighted average
                    RECL = Recommended limit
                    TLV  = Threshold limit value
                    ADI  = Acceptable daily intake
    
                    The ADI (acceptable daily intake) of PCP levels
                    established by the Safe Drinking Water Committee of
                    the National Academy of Sciences (USA) is 3 mg/kg body
                    weight per day (not to be confused with the ADI 
                    established by FAO-WHO.
    
                    PCP has been detected in the serum, urine, adipose
                    tissues, and even the seminal fluid of the general
                    population. The overall ambient exposure of an average 
                    person not occupationally exposed to PCP is about 26.3 
                    mg/kg/day (6 mg in food, 14mg in water, 4.3 mg in air, 
                    and 2 mg miscellaneous sources).  The total exposure 
                    corresponds to a dose of 0.438 mg/kg body weight per
                    day for a 60-kg person, which is below the
                    experimental threshold dose and below the acceptable
                    daily intake of PCP (3 mg/kg/day).
    
                    In isolated instances, PCP exposure can be very high,
                    causing acute and subacute intoxications of the skin
                    and  respiratory and digestive tracts.

        7.3  Carcinogenicity

             Exposure to wood treated with PCP has been associated
             with an increased incidence of Hodgkin's Disease (Greene et
             al, 1978) and non-Hodgkin's lymphoma (Bishop and Jones,
             1981).  There is epidemiological evidence that occupational
             exposure to mixtures of chlorophenols increases the risk of
             soft tissue sarcoma and lymphoma, but there is no clear
             dose-effect relationship.  The major deficiency in all of
             these studies appears to be a lack of specific exposure data,
             with the ever-present problem of impurities (WHO,
             1987).

        7.4  Teratogenicity

             The pregnancy outcomes in 43 women married to sawmill
             workers in Canada did not reveal any significant differences
             when compared with  a control group (Corddry, 1981). 
             Teratogenicity has been reported in animals (WHO, 1987) and
             PCP is considered to have a potentially deleterious effect on
             the human fetus.

        7.5  Mutagenicity

             The available data are inadequate.  Studies have
             indicated that people exposed to PCP have a slightly higher
             rate of chromosome breakage than controls.

        7.6  Interactions

             Workplace exposures are to technical PCP which usually
             contains miocrocontaminants, particularly polychlorinated
             dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzo-furans
             (PCDFs), of which H6CDD is the most important conveyer
             toxicologically.  Subacute effects such as chloracne and
             animal hepatotoxicity, fetotoxicity, and immunotoxicity are
             probably caused by these contaminants.
    
             The metabolic transformation of other chlorinated compounds,
             such as hexachlorobenzene, pentachloronitrobenzene, and gamma
             benzene hexachloride isomers (e.g., lindane) results in the
             formation of PCP (WHO, 1987).
    
             No specific interaction has been reported.  The concomitant
             administration of, or exposure to, chemicals such as
             dinitrophenols which increase the metabolic rate, may have
             synergistic effects,  The use of formulations with solvents
             based on petroleum distillates enhances absorption. 
             Hepatotoxic and nephrotoxic chemicals are additional
             hazards.

    8.  TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS

        8.1  Material sampling plan

             8.1.1  Sampling and specimen collection

                    8.1.1.1  Toxicological analyses

                    8.1.1.2  Biomedical analyses

                             Serum or blood (e.g. lithium
                             heparinate) and urine (spontaneous) and 24 h
                             fraction. 

                    8.1.1.3  Arterial blood gas analysis

                             Heparinized arterial blood sample

                    8.1.1.4  Haematological analyses

                             Blood (e.g. EDTA) for routine
                             haematological analyses

                    8.1.1.5  Other (unspecified) analyses

                             No further materials.

             8.1.2  Storage of laboratory samples and specimens

                    8.1.2.1  Toxicological analyses

                             Keep samples in the refrigerator at
                             4C until they are analyzed. Urine samples
                             can be stored up to 40 days if kept deep
                             frozen.

                    8.1.2.2  Biomedical analyses

                             Keep samples in the refrigerator at
                             4C until they are analyzed. Urine samples
                             can be stored up to 40 days if kept deep
                             frozen.

                    8.1.2.3  Arterial blood gas analysis

                    8.1.2.4  Haematological analyses

                    8.1.2.5  Other (unspecified) analyses

             8.1.3  Transport of laboratory samples and specimens

                    8.1.3.1  Toxicological analyses

                             The samples should be transported
                             immediately after collection. They should be
                             cooled about 4C.

                    8.1.3.2  Biomedical analyses

                             The samples should be transported
                             immediately after collection. They should be
                             cooled about 4C.

                    8.1.3.3  Arterial blood gas analysis

                    8.1.3.4  Haematological analyses

                    8.1.3.5  Other (unspecified) analyses

        8.2  Toxicological Analyses and Their Interpretation

             8.2.1  Tests on toxic ingredient(s) of material

                    8.2.1.1  Simple Qualitative Test(s)

                             a) Colour reaction with nitric acid
                             and tetrabase (Feigl 1966)
    

                             (1) Principle of test
    
                             Pentachlorophenol is easily converted to
                             yellow chloranil (tetrachloro-p-benzoquinone)
                             by brief warming with concentrated nitric
                             acid. The resulting chloranil is detected by
                             means of a citric acid solution of tetrabase
                             buffered with sodium acetate. A blue
                             oxidation product of tetrabase results. If
                             only small amounts of pentachlorophenol are
                             suspected, the nitrous acid or nitrogen
                             oxides must be destroyed by adding urea to
                             prevent oxidation of the tetrabase.
    
                             (2) Sampling
    
                             Take a small quantity of the suspect
                             material.
    
                             (3) Chemicals and reagents
    
                             Chemicals: (Analytical grade)
                             Concentrated nitric acid, 65% (RD 1,40)
                             Citric acid
                             Sodium acetate
                             Tetrabase, N,N,N',N',
                             Tetramethyl-4,4'-diaminodiphenylmethan (CAS
                             Nr. 101-61-1)*
                             Urea
                             Pentachlorophenol
                             Methanol
                             Reagents:
                             Tetrabase solution:
                             250 mg tetrabase and 1,0g citric acid are
                             dissolved in 10 mL water and diluted with
                             water to 50 mL.
    
                             (4) Equipment
    
                             Micro test tubes
                             Water bath
                             Volumetric flask 50 mL
    
                             (5) Sample preparation
    
                             Dissolve a small portion (about 50 to 100mg)
                             of the suspect material in 5 mL methanol;
                             filter or centrifuge if necessary.
    

                             (6) Procedure
    
                             1. Place one drop of the test solution in a
                             micro test tube and evaporate to dryness in a
                             boiling water bath.
    
                             2. Add one drop of concentrated nitric acid
                             and place for 2 min in the boiling water
                             bath.
    
                             3. Cool the test tube.
    
                             4. Add several mg of urea, followed by a drop
                             of the tetrabase solution and a pinch (tip of
                             knife blade) of solid sodium acetate.
    
                             5. Heat the mixture in the boiling water bath
                             for 2 min.
    
                             6. A blue colour indicates the formation of
                             chloranil and hence the presence of
                             pentachlorophenol in the sample.
    
                             * Supplier e.g. Alrich Chemie GmbH, D-7924
                             Steinheim, Germany Fluka Feinchemikalien
                             GmbH, D-7910 Neu-Ulm, Germany
    
                             (7). Calibration procedure
    
                             Not applicable.
    
                             (8) Quality control
    
                             It is important to carry out the test with a
                             blank (pure methanol) and a positive control,
                             using authentic pentachlorophenol.
    
                             (9) Specificity
    
                             The test is not specific, but chloranil,
                             bromanil and iodanil also give a positive
                             result. Organic peroxides like
                             benzoylperoxide also oxidize tetrabase and
                             give a blue colour.
    
                             (10) Detection limit
    
                             The detection limit is 2,5 ug
                             pentachlorophenol.
    

                             (11) Analytical assessment
    
                             This test may indicate the presence of
                             pentachlorophenol, but a confirmation test is
                             required.
    
                             (12) Medical interpretation
    
                             A positive result may indicate
                             pentachlorophenol intake.
    
                             b) Colour reaction with nitric acid/sulfuric
                             acid NaOh (WHO-1991)
    
                             (1) Principle of test
    
                             Not mentioned.
    
                             (2) Sampling
    
                             Take a small portion of the suspect material
                             or scene residues.
    
                             (3) Chemicals and reagents
    
                             Chemicals: (Analytical grade)
    
                             Sodium hydroxide
                             Concentrated nitric acid, 65% (RD 1,40)
                             Concentrated sulfuric acid, 95-97% (RD 1,83)
                             n-Butylacetate
                             Pentachlorophenol
                             Universal indicator paper
    
                             Reagents: Aqueous sodium hydroxide (2 mol/L =
                             80 g/L)
    
                             (4) Equipment
    
                             Water bath
                             Centrifuge
                             Test tubes
                             Pipettes
    
                             (5) Sample preparation
    
                             Dissolve a small portion of the sample in 5
                             mL of n-butylacetate; filter or centrifuge if
                             necessary.
    

                             (6) Procedure
    
                             1. Transfer the solution in n-butylacetate to
                             a clean tube and evaporate to dryness on a
                             boiling water bath.
    
                             2. Add 200 uL of concentrated nitric acid to
                             the residue and heat the tube in the water
                             bath for 30 seconds.
    
                             3. Cool and add 100 uL of the mixture to 2 mL
                             of concentrated sulfuric acid.
    
                             4. To the remainder of the cooled mixture add
                             2 mL water and then add sodium hydroxide
                             solution drop by drop until the pH reaches 8
                             (universal indicator paper).
    
                             5. Observe the colour reactions;
                             pentachlorophenol gives a red colour at stage
                             2 and 3 and a brown-violet colour at stage
                             4.
    
                             (7) Calibration procedure
    
                             Not applicable.
    
                             (8) Quality control
    
                             It is essential to always carry out a "blank"
                             and "positive" control alongside the test
                             sample.
    
                             (9) Specificity
    
                             Other chlorinated phenols such as
                             hexachlorophene also give a positive result
                             in this test.

                             (10) Detection limit
    
                             The detection limit is 500 mg
                             pentachlorophenol/L.
    
                             (11) Analytical assessment
    
                             This test may indicate the presence of
                             pentachlorophenol, but a confirmation test is
                             required.
    

                             (12) Medical interpretation
    
                             A positive test may indicate the presence of
                             pentachlorophenol in a suspect
                             material.

                    8.2.1.2  Advanced Qualitative Confirmation Test(s)

                             a) The gas chromatographic method of
                             Angerer and Eben (1985) described under
                             8.2.2.4a) can be applied. Hydrolysis is not
                             necessary.
    
                             b) HPLC-method for identification of
                             pentachlorophenol in air (NIOSH Method No.
                             S297, validation date: 12/23/77).
    
                             A known volume of air is drawn through a
                             mixed cellulose ester membrane filter
                             connected in series to a midget bubbler
                             containing 15 mL of ethylene glycol to
                             collect pentachlorophenol. The filter and
                             bubbler are disconnected. The filter is
                             removed from the filter holder and added to
                             the bubbler flask. Just before analysis, 10
                             mL of methanol is added to the bubbler flask.
                             The resulting sample is analyzed by high
                             performance liquid chromatography using a UV
                             detector set at 254 nm.

                    8.2.1.3  Simple Quantitative Method(s)

                             Not available

                    8.2.1.4  Advanced Quantitative Method(s)

                             Gas chromatography
    
                             The gas chromatographic method of Angerer &
                             Eben (1985) described under 8.2.2.4a) can be
                             applied.   Hydrolysis is not necessary. Refer
                             also to 8.2.2.4b.
    
                             Medical interpretation
    
                             The presence of pentachlorophenol in the
                             measured concentration has to be
                             considered.

             8.2.2  Tests for biological specimens

                    8.2.2.1  Simple Qualitative Test(s)

                             For stomach contents:
    
                             The colour reaction with nitric acid/sulfuric
                             acid and potassium hydroxide, described under
                             8.2.2.1b, can be applied to stomach contents
                             as well (WHO Manual).
    
                             (1) Principle of test
    
                             Not mentioned.
    
                             (2) Sample
    
                             Stomach contents, 10 mL.
    
                             (3) Chemicals and reagents  (Analytical
                             grade)
    
                             Sodium hydroxide
                             Concentrated nitric acid (RD 1,40)
                             Concentrated sulfuric acid (RD 1,83)
                             n-Butylacetate
                             Pentachlorophenol
                             Universal indicator paper
    
                             Reagents:
                             Aqueous sodium hydroxide, 2 mol/L = 80 g/L.
    
                             (4) Equipment
    
                             Water bath
                             Centrifuge
                             Test tubes
                             Pipettes
                             Separatory funnel
    
                             (5) Sample preparation
    
                             Extract 10 mL of stomach contents with 20 mL
                             of n-butylacetate, centrifuge and discard the
                             aqueous layer.
    
                             (6) Procedure
    
                             1. Transfer the extract to a clean tube and
                             evaporate to dryness on a boiling water
                             bath.
    

                             2. Add 200 uL of concentrated nitric acid to
                             the residue and heat the tube in the water
                             bath (30 s).
    
                             3. Cool and add 100 uL of the mixture to 2 mL
                             of concentrated sulfuric acid.
    
                             4. To the remainder of the cooled mixture add
                             2 mL water and then add sodium.
    
                             5. Observe colour reactions.
                             Pentachlorophenol gives a red colour at stage
                             2 and 3 and a brown-violet colour at stage
                             4.
    
                             (7) Calibration procedure
    
                             Not applicable.
    
                             (8) Quality control
    
                             It is essential to always carry out a "blank"
                             and "positive" control alongside the test
                             sample.
    
                             (9) Specificity
    
                             Other chlorinated phenols such as
                             hexachlorophene also react in this test.
    
                             (10) Detection limit
    
                             The detection limit is 1g
                             pentachlorophenol/L.
    
                             (11) Analytical assessment
    
                             This test may indicate the presence of
                             pentachlorophenol, but a confirmation test is
                             required.
    
                             (12) Medical interpretation
    
                             Consider the oral uptake of
                             pentachlorophenol.

                    8.2.2.2  Advanced Qualitative Confirmation Test(s)

                             For stomach contents
    
                             With the residue of an extract with
                             n-butylacetate gas chromatography can be
                             applied after (Needham et al. 1981; Angerer
                             and Eben 1985 (refer to 8.2.2.4a and b).
                             Hydrolysis is not necessary.

                    8.2.2.3  Simple Quantitative Method(s)

                             Not available.

                    8.2.2.4  Advanced Quantitative Method(s)

                             a) Quantitative determination of
                             pentachlorophenol in urine by gas
                             chromatography after acid ydrolysis,
                             extraction and derivation (Angerer and Eben,
                             1985).
    
                             (1) Principle of test
    
                             Gas chromatography after acid hydrolysis,
                             extraction and derivation.
    
                             (2) Sampling
    
                             Urine specimens are collected in glass
                             containers which have been carefully cleaned
                             with acetone.
    
                             (3) Chemicals and reagents
    
                             Chemicals: (Analytical grade)
                             Pentachlorophenol
                             Acetone for analysis of residue
                             Sodium hydroxide
                             Diethyl ether for analysis of residue
                             Sodium sulfate, anhydrous
                             Benzene for analysis of residue
                             Sodium carbonate
                             Ethanol
                             Acetic anhydride
                             Concentrated sulfuric acid, 96%
                             Ultra pure water (ASTM type 1) or
                             double-distilled water
                             Nitrogen gas, purified (99.999%)
    

                             Reagents: Aqueous sodium carbonate solution
                             0% (w/v)
                             Aqueous sodium hydroxide, 5 mol/L (200 g/L)
                             Acetylating reagent: 20 mL anhydride + 1 mL
                             concentrated sulfuric acid. This reagent is
                             prepared freshly for each test series.
    
                             Calibration standards: Solutions of
                             pentachlorophenol in ethanol with
                             concentration 20, 80, 120, 200 & 280
                             mg/L.
    
                             Control samples: Control samples are
                             commercially available, e.g. from Bio Rad
                             Laboratories, Dachauer Strasse 511, PO Box
                             50-0167, D-W 8000 Mnchen 50, Germany.
    
                             (4) Equipment
    
                             Gaschromatograph with electron-capture
                             detector (63Ni), chart recorder or
                             integrator.
                             Glass column: Length 2.2 m, inner diameter
                             2.0 mm.
                             Column packing: 8% DC 200 on Chromosorb
                             G/AW-DMCS, 100-120 mesh or Quartz capillary:
                             Length, 30 m, inner diameter 0.33 mm;
                             Stationary phase SE 30 (100% methyl
                             silicone), chemically bonded; film thickness
                             0.25 mm.
                             Syringe for gas chromatography 10 mL.
                             Water bath
                             Rotary evaporator
                             Mechanical shaker
                             Graduated glass vials with ground-glass
                             stoppers, 10 ml, 20 ml.
                             Clamps
                             Round-bottomed flasks, 50 ml
                             Sample flasks, 2 ml, with rolled rims and
                             special pliers for putting on and taking off
                             the PTFE-lined caps.
                             Volumetric flasks, 50 ml, 100 ml.
                             Graduated pipettes, 10 ml
                             Transfer pipettes, 0,5, 1, 2, 3, 5, 7ml.
    
                             (5) Specimen preparation
    
                             No special preparation is necessary.
    

                             (6) Procedure
    
                             1. 1 ml of urine is pipetted into a 20ml
                             graduated glass vial with a ground stopper,
                             and 0,5ml of 37% hydrochloric acid is
                             added.
    
                             2. The vial is clamped, tightly shut and
                             placed in a boiling water bath for 1 h.
    
                             3. After the sample has cooled to room
                             temperature, 1 ml of the sodium hydroxide
                             solution (0,5 mol/L) is added. (The pH must
                             remain below 7).
    
                             4. The solution is extracted four times with
                             5 mL of diethyl ether.
    
                             5. The extracts are combined in a 50 mL
                             round-bottomed flask and dried over anhydrous
                             sodium sulfate.
    
                             6. The extracts are filtered and gently
                             reduced in volume to about 1 mL in a second
                             round-bottomed flask on a rotary evaporator
                             (30 C).
    
                             7. Dry nitrogen gas is passed over this 1 mL
                             to remove the remaining solvent.
    
                             8. The residue is dissolved in 2 mL benzene.
    
                             Derivation:
    
                             9. 1 mL acetylating reagent is added to the
                             residue and this mixture is incubated in a
                             water bath at 5 C for 30 min.
    
                             10. The mixture is cooled to room
                             temperature; than excess acetylating reagent
                             is removed by adding slowly 18 mL 10% sodium
                             carbonate solution and shaking thoroughly (at
                             first manually, then 10 min on a mechanical
                             shaker).
    
                             11. The mixture is transferred to a graduated
                             glass vial (20 mL) and left to stand for 15
                             min to allow phase separation.
    

                             12. The organic phase is pipetted into a
                             graduated glass vial (10 mL), mixed briefly
                             with 5 mL 10% sodium carbonate solution, and
                             left to stand for 1 h.
    
                             13. The organic phase is transferred to a
                             glass vial (5 mL) with screw cap into which
                             anhydrous sodium sulfate has been placed for
                             drying.
    
                             14. After a few hours (or the next day) the
                             organic phase is transferred to a 2 mL
                             rolled-rim sample flask.
    
                             15. The tightly shut flask is stored in the
                             deep freeze until analysis.
    
                             16. With each test series, reagent blanks
                             should be prepared in which ultra pure water
                             is used instead of urine.
    
                             Gas chromatography:
    
                             a) Packed columns
    
                             Temperatures: column 180C; injection block
                             210C; detector 350C.
                             Carrier gas: purified nitrogen, flow rate 30
                             mL/min
                             Sample volume: 10 mL
                             Retention time: 16.8 min.
    
                             b) Capillary column
    
                             Temperatures: column 160 C; injection block
                             250 C; detector 300 C.
                             Split: 1:20
                             Carrier gas: purified nitrogen, flow rate 2
                             mL/min; make up gas 40 mL/min.
                             Sample volume: 10 mL
                             Retention time: 22.6 min
    
                             (7) Calibration procedure and calculation of
                             results
    
                             A 1 mL sample of each calibration standard is
                             analyzed as described. The peak area (after
                             substraction of the value for the reagent
                             blank) is plotted as a function of the
                             concentration of the standard to give a
                             calibration curve.
    

                             The concentration of pentachlorophenol in the
                             urine sample is read off the calibration
                             curve (after substraction of the value for
                             the reagent blank).
    
                             (8) Quality control
    
                             A control sample whose analyte concentration
                             is known is processed with each analytical
                             series.
    
                             (9) Specificity
    
                             No other substances should interfere with
                             pentachlorophenol. The method is specific
                             because of the deriatization. Other
                             chlorinated phenols like Lindane ore
                             hexylresorcinol are separated from
                             pentachlorophenol.
    
                             (10) Detection limit
    
                             The limit of detection is 9.0 mg
                             pentachlorophenol per litre urine.
    
                             (11) Analytical assessment
    
                             a) To determine the within-series
                             imprecision, a sample of a stock solution
                             containing pentachlorophenol in the
                             concentration of 4 mg/l in ethanol was
                             diluted about 20-fold with pooled urine from
                             unexposed persons. The resulting urine sample
                             with the concentration of 209 m/L was
                             analyzed eight times. The relative standard
                             deviation was 1.9%.
    
                             Recovery experiments were performed with
                             urine samples spiked with pentachlorophenol
                             in concentrations between 83.6 and 292.6 m/L.
                             The recovery rates were between 92 and
                             100%.
    
                             b) Quantitative determination of
                             pentachlorophenol in whole blood or serum by
                             gas chromatography after acetylation (Needham
                             et al. 1981).
    

                             This method includes acidification and
                             extraction with hexane. The extract is
                             reacted with acetic anhydride and injected
                             into a gas chromatograph.
                             Column: 3% OV-101
                             Detector: ECD
    
                             This method can also be applied to urine
                             after hydrolization.

                    8.2.2.5  Other Dedicated Method(s)

             8.2.3  Interpretation of toxicological analyses

                    For man, the acute lethal oral dose is
                    approxiamtely 30 mg PCP per kg body weight. First
                    manifestations of  toxicity appear at concentrations
                    above 1 mg/L of  pentachlorophenol in blood or urine.
                    The first symptoms  of serious poisoning are seen at
                    concentrations of 3 to  10 mg PCP per litre urine and
                    40 to 80 mg per litre  blood.  The following data may
                    help to interprete  analytical results in detail:
    
                    Urine
    
                    Adults
    
                    General population, not exposed         0.01 mg/l
    
                    Not occupationally exposed general      0.04 mg/l
                    population
    
                    Occupationally exposed workers          1.0  mg/l
                    (WHO, 1987)
    
                    BAT* Value 1994 (DFG 1991)              0.3  mg/l
    
                    Signs of systemic toxicity              > 1.0  mg/l
                    (refer to 10.2.3)
    
                    18 wood-treatment workers               1.31 g/l
                    (Begley et al. 1977) 
    
                    Fatal intoxications (Baselt 1982)       28 to 520 mg/l
    
                    Children
    
                    Dermal exposure in bath water, symptoms 60 mg/l
    

                    Blood
    
                    Adults
    
                    Signs of systemic toxicity              > 1 mg/l 
                    (refer to 10.2.3)
    
                    7 exposed workers                       0.34 to 6 mg/l
                    (Bevenue et al. 1968) 
    
                    Chronic occupational exposure,          > 4mg/l 
                    borderline effects 
                    (refer to 7.2.1.1)
    
                    18 exposed workers                      5.14 mg/l
                    (Begley et al. 1977) 
    
                    Usually toxic (Clarke 1986)             > 30 mg/l
    
                    Signs of systemic poisoning             > 40 to
                    (refer to 8.2)                          80 mg/l
    
                    Intake of 11g PCP, death 4h later       39 mg/l
                    (Burger 1936)
    
                    Acute intoxications survived:           115 mg/l 
                    (Young and Haley 1978)
    
                    Several cases with fatal outcome        46 to 173 mg/l
                    (Gordon 1956, Blair 1961, Mason  
                    et al. 1965, Clarke  1969, Baselt 
                    1982; refer also to 7.2.1.1)
    
                    (* Biological Tolerance Values for Working Materials)
    
                    Serum, plasma
    
                    Adults
    
                    General population, not exposed          < 0.030 mg/l
                    (Angerer) 
    
                    4h after oral intake of 1 mg/kg Na-PCP   0.2 mg/l
                    (Braun et al. 1979)
    
                    Non-occupational (high) exposure of      0.05 to 
                    general population  (Baselt 1982)        1.0 mg/l
    
                    Healthy exposed workers                  0.9 to 
                    (Bevenue et al. 1988)                    9.1 mg/l 
    
                    Acute intoxication (survived),           150 mg/l 
                    5h after ingestion (Haley 1977)
    

                    Children
    
                    Contamination of nursery linens in a     7 to 118 mg/l
                    children's hospital (Armstrong 1969;
                    refer also to 7.2.1.1)

        8.3  Biomedical investigations and their interpretation

             8.3.1  Biochemical analysis

                    8.3.1.1  Blood, plasma or serum

                             Sodium, potassium, glucose,
                             creatinine (urea) Alanine aminotransferase,
                             aspartate aminotransferase, bilirubin.
                             Percentage of methaemoglobin. In case of
                             chronic exposure:  Immunoglobulin A and
                             G.

                    8.3.1.2  Urine

                             Total protein and qualitative
                             testing for haemoglobin. Total porphyrins and
                             delta-aminolevulinic acid.

                    8.3.1.3  Other fluids

                             No dedicated test.

             8.3.2  Arterial blood gas analyses

                    pH, pCO2, pO2, base excess, actual HCO3-,
                    O2-saturation.

             8.3.3  Haematological analyses

                    Red and white blood cell count; haemoglobin,
                    haematocrit. In case of chronic exposure:
                    T-cell-count.

             8.3.4  Interpretation of biomedical investigations

                    In case of acute severe pentachlorophenol
                    poisoning hepatic and renal dysfunction develop:
                    Activity of alanine aminotransferase, aspartate 
                    amino-transferase, gamma-glutamyltransferase rises, as
                    well as the concentration of creatinine and urea.
                    Metabolic  acidosis is observed and
                    methaemoglobinaemia.  Haematuria. In case of chronic
                    (?) exposure secondary  porphyria may be observed and
                    signs of T-cell suppression. Further research on
                    porphyria in pentachlorophenol intoxication is needed
                    (refer to  section 9.4.5)

        8.4  Other biomedical (diagnostic) investigations and their 
             interpretation

             ECG-recording (refer to section 9.4.1).

        8.5  Overall Interpretation of all toxicological analyses and 
             toxicological investigations

             Sample collection
    
             Collect blood and urine for biomedical analysis and PCP
             determination.
    
             Take a sample of the product for identification.
    
             Biomedical analysis
    
             Routine blood analysis, especially blood gases, pH,
             electrolytes, BUN and creatinine, hepatic enzymes, and blood
             count.  Evaluation of kidney and liver function is
             recommended.
    
             Urinalysis (albuminia, casts, haematuria, volume).
    
             ECG monitoring.
    
             Toxicological analysis
    
             Determine PCP in urine or blood.
    
             Signs of systemic toxicity appear in the majority of cases
             when the urine and blood levels reach 9.1 mg/100 ml or 1
             ppm.

        8.6  References

    9.  CLINICAL EFFECTS

        9.1  Acute poisoning

             9.1.1  Ingestion

                    Nausea, vomiting, colic, and intense thirst
                    follow PCP ingestion. Cases of PCP ingestion are
                    unusual but often result in acute systemic
                    poisoning.
    
                    Ingestion causes gastric and intestinal inflammation;
                    however, the severity of the inflammation depends on
                    the carrier solvent and the presence of other
                    chemicals.
    

                    Pulmonary oedema and congestion have been reported
                    occasionally after oral exposure if aspiration of
                    ingested PCP has occurred.

             9.1.2  Inhalation

                    Bronchitis and severe airway obstruction may
                    occur after massive exposure.  Tachypnoea and cyanosis
                    indicate a poor prognosis. In some cases, systemic
                    poisoning is caused by high exposure.

             9.1.3  Skin exposure

                    Skin irritation is a common feature in PCP
                    intoxication; generalized itching and burning
                    dermatosis may occur.  Systemic poisoning may result
                    from cutaneous absorption.

             9.1.4  Eye contact

                    Local symptoms:  painful irritation of the
                    eyes, and of the mucous membranes of the nose and
                    throat occurs after exposure to airborne toxic levels
                    of PCP and to contact with dusts or vapours.

             9.1.5  Parenteral exposure

                    No data available.

             9.1.6  Other

                    No data available.

        9.2  Chronic poisoning

             9.2.1  Ingestion

                    Not relevant.

             9.2.2  Inhalation

                    Virtually all workers exposed to airborne
                    concentrations take up PCP through the lungs and
                    skin.

             9.2.3  Skin exposure

                    In addition to airborne concentrations, workers
                    who handle treated lumber or who maintain
                    PCP-contaminated equipment are at risk pf absorption
                    of PCP via the skin.  They may absorb from 50% (based
                    on urinary PCP levels) to 70% (based on serum levels)
                    of their total PCP burden through their skin.

             9.2.4  Eye contact

                    Eye irritation is usually observed.

             9.2.5  Parenteral exposure

                    Unknown.

             9.2.6  Other

                    Unknown.

        9.3  Course, prognosis, cause of death

             Increasing anxiety and restlessness, together with an
             increased rate and depth of respiration, cyanosis,
             tachycardia, diarrhoea, rise in body temperature, and,
             eventually, convulsions and coma are signs of more severe PCP
             poisoning.
    
             Death is due to cardiac arrest and victims usually show an
             immediate onset of marked rigor mortis.

        9.4  Systematic description of clinical effects

             9.4.1  Cardiovascular

                    Tachycardia has been reported in acute PCP
                    poisoning, with a rise in metabolic rate.  In severe
                    cases of poisonings death is due to cardiac
                    arrest.

             9.4.2  Respiratory

                    Hyperpnoea, tachypnoea, and dyspnoea, can be
                    observed in systemic poisoning.
    
                    Pulmonary oedema and congestion have been reported
                    after inhalation, and, occasionally, after ingestion,
                    if aspiration of ingested PCP occurs (WHO,
                    1987).

             9.4.3  Neurological

                    9.4.3.1  Central nervous system (CNS)

                             Ataxia, mental and physical fatigue,
                             headaches, dizziness, disorientation.  Unlike
                             the lower phenols, PCP usually does not cause
                             convulsions (WHO, 1987).
    
                             Chronic exposure causes neurasthenia,
                             depression and headaches.

                    9.4.3.2  Peripheral nervous system

                             Sensory nerve conduction was reduced
                             in a group of exposed workers but this was
                             not correlated with PCP levels.  In a recent
                             study, no significant signs of peripheral
                             neuropathy were reported (Triebig et al
                             1981).
    
                             Vertigo and insomnia have been reported in
                             non-acute effect exposures (WHO,
                             1987).

                    9.4.3.3  Autonomic nervous system

                             Profuse sweating occurs in acute poisoning.

                    9.4.3.4  Skeletal and smooth muscle

                             Muscular asthenia is reported.

             9.4.4  Gastrointestinal

                    When ingested, PCP causes severe irritation,
                    vomiting, and abdominal pain.  Even when not ingested,
                    PCP exposure can cause gastrointestinal
                    symptoms.

             9.4.5  Hepatic

                    There is no conclusive evidence that
                    significant liver damage occurs.  Elevation of serum
                    concentrations of  some hepatic enzymes is transient. 
                    Abnormal porphyrin metabolism and indicators of
                    hepatotoxicity have been  reported after acute
                    poisonings (Jirasek et al 1974) and hepatic damage can
                    be seen after acute poisoning (Bozza-Marrubini, 1987).
                    Effects involving the liver may be due to
                    contaminants.  Further research is needed.

             9.4.6  Urinary

                    9.4.6.1  Renal

                             Functional changes in the kidneys
                             (reduction in creatinine clearance and
                             resorption of phosphorus) have been reported
                             (WHO, 1987).  Kidney failure can occur after
                             severe acute poisoning (Bozza-Marrubini,
                             1986).

                    9.4.6.2  Others

             9.4.7  Endocrine and reproductive systems

                    Hyperglycaemia and glycosuria may occur in
                    cases of acute poisoning (Bozza-Marrubini, 1987).
    
                    Information about the effects of PCP on male
                    reproduction is inconclusive.  Male fertility has not
                    been studied (WHO, 1987) although Corddry (1981)
                    investigated women married to sawmill workers and no
                    significant effect on the outcome of
                    pregnancy.

             9.4.8  Dermatological

                    Chloracne, skin pustular eruptions, eczema,
                    rashes, inflammation of the skin, and subcutaneous
                    lesions are common (WHO, 1987).  Klemmer et al(1980)
                    reported low-grade infection or inflammation of the
                    skin and subcutaneous tissue.

             9.4.9  Eye, ears, nose, throat: local effects

                    Eye irritation
    
                    Painful nasal irritation occurs when workers are
                    exposed to more than 1 mg/m3.  Workers accustomed to
                    exposure may acquire a higher threshold for irritation
                    and may be able to tolerate up to 2.4 mg/m3.
    
                    Throat irritation can occur.

             9.4.10 Haematological

                    Aplastic anaemia and decreased haematocrit
                    have been associated with PCP use (WHO,
                    1987).

             9.4.11 Immunological

                    Marked T-cell suppression has been reported in
                    patients exposed to phenols, which are thought to be
                    immunotoxic.
    
                    Animal studies indicate that PCP is not strongly
                    immunotoxic but confirm that exposure can lead to
                    immunological changes (WHO, 1987).

             9.4.12 Metabolic

                    9.4.12.1 Acid-base disturbances

                             Metabolic acidosis may occur due to
                             hepatic and renal dysfunction and marked
                             respiratory symptoms (Hayes,
                             1982).

                    9.4.12.2 Fluid and electrolyte disturbances

                             Dehydration and electrolyte loss
                             occur in severe poisoning.

                    9.4.12.3 Others

                             Unknown.

             9.4.13 Allergic reactions

                    Not described.

             9.4.14 Other clinical effects

                    Not relevant.

             9.4.15 Special risks

                    From experiments in rats it is generally
                    agreed that PCP is fetotoxic but it does not appear to
                    be a teratogen.
    
                    Analysis of data from 43 women who had a total of 100
                    pregnancies, did not show any significant differences
                    in the pregnancy outcomes of women living with
                    "exposed" men versus "unexposed" men.
    
                    PCP was detected (100 to 200 ppb) in 50 samples of
                    human seminal plasma analysed.  Male fertility was not
                    studied.
    
                    Samples of human milk contained between 0.03 and 1.8
                    mg/kg, which is considerably less than PCP levels
                    usually found in other body fluids or
                    tissues.

        9.5  Other

             Not relevant.

        9.6  Summary

    10. MANAGEMENT

        10.1 General principles

             Remove the patient from further exposure.
    
             Patients who have been poisoned should be admitted to
             hospital for assessment and treatment.
    
             No specific treatment or antidote is known.
    
             Continuous administration of oxygen, replacement of fluids,
             and control of hyperthermia by physical means (cold sponging
             or spraying) are the general principles of treatment. 
    
             Salicylates are contraindicated.
    
             Skin: All clothing that might be contaminated should be
             removed.  Wash the skin thoroughly with soap and water.
    
             Eyes:  Flush immediately with water for 15 min.
    
             Inhalation:  remove patient to fresh air, keep at rest, and
             watch for respiratory failure.  Give artificial respiration,
             if needed.  Absolute rest is essential.
    
             Do not give milk or fatty foods that promote absorption.
    
             Ingestion: Do not induce vomiting.  Because PCP is usually
             dissolved in petroleum distillates, vomiting involves a risk
             of aspiration with consequent pneumonia or chemical
             pneumonitis. Gastric lavage may be necessary in hospital,
             followed by activated charcoal and a saline cathartic.

        10.2 Life supportive procedures and symptomatic treatment

             No specific antidote or treatment is known; 
             symptomatic and supportive measures are the basis for
             treatment, irrelevant of the route of exposure or
             absorption.
    
             Hospitalization and rest are essential.
    
             Control hyperthermia with sponging, or with baths in lukewarm
             water.  Antipyretics are not recommended, because they are
             likely to enhance the toxicity of phenolic compounds.
    
             Support circulation and ventilation: establish a clear airway
             and tissue oxygenation by aspiration of secretions, and by
             assisted pulmonary ventilation.
    

             Note that lung oedema may occur after a few hours and may be
             aggravated by physical effort.
    
             Replacement of fluids (look for cerebral oedema) checking
             electrolytes and acid-base balance.
    
             Urine alkalinization, forced diuresis, and exchange
             transfusion may be considered.
    
             Cholestyramine can bind PCP in the gastrointestinal tract and
             prevent absorption.  Cholestyramine may be administered as a
             suspension in water at a dose of 80 mg/kg three times per
             day.
    
             Local treatment for burns and skin lesions (after
             decontamination).
    
             Local treatment for eye irritation (after decontamination).

        10.3 Decontamination

             If ingested:
    
             Induce emesis with ipecac syrup only if the patient is alert
             and has a cough reflex.  Note that solvents of commercial
             formulations of PCP are usually petroleum distillates. 
             Administer activated charcoal in slurry up to every 4 h. 
             Note if aspiration of ingested PCP has occurred.
    
             Gastric contents may be evacuated with gastric lavage if
             emesis has failed or if the patient is unconscious.  Proceed
             with care and use a cuffed endotracheal tube.  Water or
             isotonic saline (0.9% sodium chloride) or 5% sodium
             bicarbonate may be used.  When the liquid of the lavage
             returns with no colour or odour, give a slurry of activated
             charcoal.  Activated charcoal may be repeated every 4 h.
    
             Administer a cathartic such as sodium sulphate (30 g in 250
             ml water).  Use with care in dehydrated patients or where
             there is a high risk of dehydration.
    
             Cholestyramine may be administered as a suspension in water
             at a dose of 80 mg/kg, three times a day.
    
             If inhaled:
    
             Remove the patient immediately from the contaminated area to
             fresh air. Support respiration, provide a clear airway and
             keep patient at rest.  The symptoms of lung oedema do not
             become apparent until a few hours later, and are aggravated
             by physical effort.  Administration of a
             corticosteroid-containing spray should be considered. 

             Monitor pulmonary manifestations after emesis or gastric
             lavage for at least 72 h.  Radiographic examination of lungs
             should be routine in these cases.
    
             Skin contact: Remove all contaminated clothing, including
             shoes and socks. Wash skin and hair with soap and water. 
             Treat burns and skin lesions locally.
    
             Eye contact: Eyes should be flushed with water at least for
             15 min.  Local treatment may be needed; consult
             ophthalmologist.

        10.4 Enhanced elimination

             To enhance elimination, alkalinise the urine by
             administration of 2 mEq/kg of sodium bicarbonate
             intravenously (Uhl et al, 1986).
    
             Forced diuresis with frusemide and mannitol has been
             considered (Young and Haley, 1978).
    
             Haemodialysis and peritoneal dialysis are not effective
             because of the high protein binding and poor water solubility
             of PCP.
    
             Exchange transfusion has proved useful in children (Robson et
             al 1969).

        10.5 Antidote treatment

             10.5.1 Adults

                    No data available.

             10.5.2 Children

                    No data available.

        10.6 Management discussion

             The management of PCP poison cases depends on moving
             the patient from the exposure, the early recognition of signs
             and symptoms, and the proper evaluation of the clinical
             condition.
    
             Since a large number of cases involve woodworkers,
             occupational conditions should be controlled, and heavy
             exposures must be monitored.  As a rule, the use of safety
             equipment (respiratory protection, safety glasses, regular
             change of clothing, and protective gloves) are recommended. 
             When PCP poisoning occurs in industry, the dermal and
             respiratory routes are the main routes of entry.
    

             Exposure of the general population to low levels of PCP is
             common, but the hazards of PCP-containing formulations in the
             household can usually be quite high, and all routes of entry
             are possible.
    
             When selecting treatment, consider: 
    
             Biliary excretion and the consequent resorption from the
             gastrointestinal tract (use of activated charcoal every 4 h
             and use of binding agents, as cholestyramine).
    
             The enhancement of excretion (urinary alkalinization, forced
             diuresis, and exchange transfusion).
    
             Correct evaluation of clinical conditions and laboratory
             facilities, as PCP monitoring in blood and urine are
             essential.
    
             Local washing of eyes and skin.  Membranes of the respiratory
             tract (as bronchial lavage) requires the care of a
             specialist.

    11. ILLUSTRATIVE CASES

        11.1 Case reports from literature

             Haley (1977) reported one case of ingestion. A
             71-year-old Japanese man intentionally ingested 113 to 226 g
             of weed killer containing 12% PCP. Although he was treated
             with gastric aspiration and lavage within the next hour, a
             substantial amount of PCP must have already been absorbed, as
             indicated by the high serum level of 150 mg/l of PCP 5 h
             after the incident. Forced diuresis with furosemide and
             mannitol substantially increased the urinary excretion of
             PCP.  The serum level of the patient, who survived, decreased
             to 12 mg/l 27 days after the ingestion.
    
             Menon (1958) reported 9 deaths from chronic occupational
             exposure to PCP. The major symptoms were hyperthermia,
             sweating, abdominal pain, dyspnoea, and muscular spasms.
             Blair (1961) also reported several deaths from occupational
             exposure to PCP.
    
             Robson et al (1969) and Armstrong et al (1969) reported
             poisonings in infants in a nursery PCP-treated diapers. 
             There were 20 cases of intoxication with 2 fatalities.

    12. ADDITIONAL INFORMATION

        12.1 Specific preventive measures

             PCP and Na-PCP must be handled with caution. 
             Inhalation of vapours and dust, skin contact with solutions,
             and ingestion, even of trace amounts, should be avoided.
    
             The nose, eyes, and mouth should be protected (by a
             respirator, folded gauze, or goggles).
    
             Rubber gloves (not cotton) are recommended.
    
             All clothing should be laundered after each use.
    
             Routine precautions: wash hands, arms, and face with soap and
             water before eating, drinking, or smoking.  Shower at the end
             of each shift and change into clean clothing.

        12.2 Other

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        American Conference of Governmental Industrial Hygienists,
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        Angerer J, Eben A (1985)  Chlorophenols
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    14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE 
        ADDRESS(ES)

        Author:      Professor A. Furtado Rahde
                     Poison Center of Porto Alegre
                     Rua Riachuelo 677/201
                     90010 Porto Alegre
                     Brazil
    
                     Tel: 55-512-275419
                     Fax: 55-512-391564
    
        Date:        February 1987
    

        Reviewer:    Dr D. Kuhn
                     Centre Anti-poisons
                     BP 15
                     1 rue Joseph Stallaert
                     1060 Brussels
                     Belgium
    
                     Tel: 32-2-3454545
                     Fax: 32-2-3475860
    
        Date:        October 1988
    
        Peer review: Hamilton, Canada
    
        Date:        May 1989
    



    See Also:
       Toxicological Abbreviations
       Pentachlorophenol (EHC 71, 1987)
       Pentachlorophenol (HSG 19, 1989)
       Pentachlorophenol (ICSC)
       Pentachlorophenol (IARC Summary & Evaluation, Volume 53, 1991)