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 30-40°C, 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 130-170°C.
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
100°C)
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 25°C) 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 360°C; heating of the sodium
salt to 280°C 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
4°C 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
4°C 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 4°C.
8.1.3.2 Biomedical analyses
The samples should be transported
immediately after collection. They should be
cooled about 4°C.
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 München 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 180°C; injection block
210°C; detector 350°C.
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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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