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OCR for page 33
PENTACELOROPHENOL
BACKGROUND INFORMAT ION
Pe ntach lorophenol ( commonly c al led penta) is a white cry s tat or powder
formulated by chlorinating molten phenol in the presence of a
catalyst. The production of this material results in other
condensation products, particularly polychlorinatet dioxins and furane.
Pentachlorophenol is used primarily in wood preservation. In
1977, 50 million pounds were produced, of which 80 percent was used
for wood preservation, ant most of the remainder was used in fungicide
products applied to leather, burlap, masonry, cordage, paint, and
paper. Although pentachlorophenol can be applied to soil to control
termites, as a tenmiticide it has been limited to specific situations,
such as direct application to termite-infested wood structures that
cannot be easily replaced.
Physical and chemical properties of pentachlorophenol are shown in
Table 1.
SUMMARY OF TOXICITY INFORMATION
Several comprehensive reviews on pentachlorophenol are availabl e (NRC,
1977b; IARC, 1979; EPA, 1979e; Rao, 1978~. Information on the
toxicity 0 f pentachloropenol is compl icated by the presence of
contaminants, such as dibenzo-=dioxins and dibenzofurans, in
technical pentachloropt~enol samples. Several studies beve shown that
much of the toxicity of pentachlorophenol can be attributed to the
presence of these contaminants (Goldatein et al., 1977; Johnson et
al., 1973; Kimbrough and Linder, 1975; McConnell et al., 1980; Schwetz
_ al., 1973~. Therefore, interpretation of the results of toxicity
studies with pentachlorophenol must consider the chemical composition
of the pentachloropenol supples tested.
EFFECTS IN MU - NS
The toxic effects of peneachlorophenol are associated with uncoupling
o f oxidat ive pbo ~ pory1 at ion. Cherac teris t ic obe errant ions inc lude
lose of appetite, respiratory difficulties, hyperpyrexia, sweating,
dyspoea, and coma (Heron, 1958~.
Pentachloropenol is readily absorbed through the skin. Twenty
infants became ill and two died after coming into contact with nursery
linens that bat been washed with a laundry product containing the
sodium salt of pentachloropenol (Armatrong et al., 1969~. The
clinical features were characteristic of an increased metabolic rate
and included tachycardis, tachypnes, fever, sweating, and acidosis.
Only a few reports in the literature have deacribet the effects of
airborne exposure to pentachlorophenol, and these did not report the
extent of exposure. Eighteen workers involved in treatment of wood
products with pentachlorophenol were studied by Begley et al. (1977~.
OCR for page 34
Renal~clearance tests (creatinine and phosphorus) were conducted on
the last day of a work period, the twentieth day of a vacation, and
the fifty-firat day after return from vacation. Pentachlorophenol was
also measured in the blood and urine. Results of renal clearance
tests were reported to be below normal in 16 of the workers before the
vacation. Results returned to normal in all but sixworkere by the
end of vacation. Clearance had again decreased 51 d after return to
work, but not to the extent observed before vacation. B1 Cod and
urinary pentachlorophenol concentrations decreased by 56 percent by
the end of vacation.
Bergner et al. (1965) reported five cases of poisoning in workers
with respiratory end dermal exposure to pentachlorophenol. Clinical
symptoms included sweating, weight lose, gastrointestinal complaints,
and hyperpyrexia; there was one fatality. Urinary pentachlorophenol
in the four survivors ranged from 2.4 to 17.5 mg/L.
Bander and Bauer (1951) described effects in 10 workers involved
in pentachlorophenol production. Exposure to other chlorinated benzol
derivatives also occurred. Symptoms included eye irritation,
bronchitis, and acne. In some of the workers, acne did not develop
until several months after exposure ended. In nine of the workers,
acne was still present in various degrees more than a year later.
EFFECTS IN ANIMALS
Acute Exposure
The oral LDso of pentachlorophenol for rats is 146~175 mg/kg, and
the dental LD,o is 320~330 mg/kg (Gaines, 1969). Symptom of
intoxication include accelerated respiration, vomiting, increased body
temperature, tachycardia, neuromuscular weakness, and cardiac failure.
Su bchronic Exposure
Several studies have reported on oral administration of
pentachlorophenol for 90 d. Knudeen et al. (1974) administered
pentachlorophenol in the diet to Wistar rats at 0, 25, 50, and 200 ppm
(0, 1.25, 2.5, and 10 mg/kg per day, respectively). At 200 ppe,
growth rate was reduced in females and liver weight was increased in
males. At 50 ant 200 ppe, hemoglobin was increased at 6 wk. but
decreased by 11 wK. No adheres effects were on served at 25 ppm.
Kimbrough and Linder (1975) gave male rate pure or technical
pentachloropbenol at 1,000 ppm. Pathologic changes in the liver were
observed and were of ~ greater magnitude with the technical sample.
Spragu - Dawley rats given technical pentachlorophecol at 3 mg/kg per
day hat increased liver and kidney weights (Johnson ee al., 1973).
When the sample was purified to reduce the amount of tioxins, no
effects were seen at this dosage.
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OCR for page 35
Chronic Exposure and Care inogenic ity
The potential carcinogenicity of pentachlorophenol was studied by
Innes et al. (1969) and by Schwetz et al. (19781. Both studies failed
to reveal any increased incidence of neoplasia. In the Schwetz et al.
( 1978) study, Sprague-Dawley rats were given a pentachloropbenol
sample (having a lower content of nonphenolice than does technical
pentachlorophenol) in the diet at 0, 1, 3, 10, and 30 mg/kg of body
weight per day; males were exposes for 22 ma, and females for 24 mot
No ~ ignif icant increas e in tumors was obeyed a t any dosage. No
toxic effects were observed in male rate at 10 mg/kg per day or less
or in females at 3 mg/kg per day or less.
In the other study (Innes et al., 1969), two strains of mice were
given commercial pentachloropbenor~impurities not specified) by
stomach tube at 46.4 mg/kg of body weight from 7 to 28 d of age and
then at 130 mg/kg in the diet for up to 78 wk. No significant
increase in tumors was observed.
Teratogenicity and Reproductive Effects
Schwetz et al. (1974) analyzed the effects of purified and commercial
grades of pentachloropt~enol on rat eetbryonal and fetal development.
Sprague-l)awley rats were given pure pentachlorophenol or a commercial
grade at 5, 15, 30, and 50 mg/kg of body weight on days 6-15 of
gestation. Embryotoxicity and fetotoxicity--as indicated by such
effects as resorption, subcutaneous edema, and anomalies of the skull,
ribs, and vertebrae~were obeer~red at 15 mg/kg and greater. The
no-obeerved-adveree-effect dosage for commercial pentachlorophenol was
5 mg/icg; delayed ossification of the skull was observed with purified
pentachlorophenol at this dosage. In a second study, Schwetz et al.
(1978) reported that a purified grade of pentachlorophenol given to
rats in the diet at 3 mg/kg of body weight for 62 t before mating,
during 15 d of mating, and throughout gestation and lactation had no
effect on reproduction or neonatal survival, growth, or development.
At 30 mg/kg, there was a reduction in body weight among~adult rats and
a decrease in neonatal sur~riva1 and growth.
Larsen _ al. (1975) reported a reduction in fetal weight when CD
rats were given an oral dose of pentachlorophenol at 60 mg/kg of body
weight on days B-13 of gestation. Fetal deaths and resorptions were
observed in hamsters when doses of 5~20 mg/kg were given on days 5-10
of gestation (Hinkle, 1973~; no effects were reported at 1.25 or 2.5
mg/kg.
Mu tagenic ity
Vogel and Chandler ( 19 74) reported that pentachlorophenol did not
induce sex-linked recessive lethale in Drosophila melanogaster.
— 35 —
OCR for page 36
Toxicokinet ice
Pentachlorophenol is excreted primarily in the urine in the free form
(75 percent); other metabolic products include tetrachlorohydroquinone
and glucuronide conjugates (Ahlborg et al., 1974; Ahlborg and
~hunberg, 1978~. Metabolism of pentachiorophenol is mediated by
microsomal enzymes.
Pentachiorophenol is eliminated from the body fairly rapidly.
Braun and Sauerhoff (1916) and Braun et al. (1977) reported chat,
after a dose of 10 mg/kg body weight, the plasma half-life is 15 ~ in
rats and 78 h in monkey e. Tissue concentrations of pentachlorophenol
were highest in the 1 iver and kidneys.
EX ISTING GUIDELINES AND STANDARDS
On the bests of a 90-d feeding study (Johnson et al., 1973) in which a
no-obeerved-adverse-effect level of 3 mg/kg per day was reported, the
NRC (1977b) calculated a no-adverse-effect-level in drinking water of
0.021 mg/L, for a 70-kg man consuming water at 2 L/d with the
assumption that 20 percent of the total intake of pentachlorophenol
would be from water. fine EPA (1979e) has suggested art ambient~water
quality criterion for pentachloropenol of 0.14 mg/L.
The ACGIH (1981) has recommended a TLV-TWA of 0.5 mg/~3 and a
ILV-STEL of 1.5 mg/~3. The OSIlA (1981) permissible workplace
exposure ~ imit is
nenta chloro cheno 1
O.S mg/~3. Both agencies noted that
,~ , is absorbed through the akin and that dental
exposure should therefore be avoided.
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Representative terms from entire chapter:
toxic effects
