EPA-540/1-86-043
Environmental Protection
Agency
Office of Emergency and
Remedial Response
Washington DC 20460
Off'ce of Research and Development
Office of Health and Environmental
Assessment
Environmental Criteria and
Assessment Office
Cincinnati OH 45268
Superfund
ŁEPA
HEALTH EFFECTS ASSESSMENT
FOR PENTACHLOROPHENOL
Do not remove. This document
should be retained in the EPA
Region 5 Library Collection.
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EPA/540/1-86-043
September 1984
HEALTH EFFECTS ASSESSMENT
FOR PENTACHLOROPHENOL
U.S. Environmental Protection Agency
Office of Research and Development
Office of Health and Environmental Assessment
Environmental Criteria and Assessment Office
Cincinnati, OH 45268
U.S. Environmental Protection Agency
Office of Emergency and Remedial Response
Office of Solid Waste and Emergency Response
Washington, DC 20460
pr Section Agency
230 So:jln t/..~f ;::-••'•
Chicago, Illinois €0604
rest
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DISCLAIMER
This report has been funded wholly or 1n part by the United States
Environmental Protection Agency under Contract No. 68-03-3112 to Syracuse
Research Corporation. It has been subject to the Agency's peer and adminis-
trative review, and 1t has been approved for publication as an EPA document.
Mention of trade names or commercial products does not constitute endorse-
ment or recommendation for use.
11
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PREFACE
This report summarizes and evaluates Information relevant to a prelimi-
nary Interim assessment of adverse health effects associated with
pentachlorophenol. All estimates of acceptable Intakes and carcinogenic
potency presented In this document should be considered as preliminary and
reflect limited resources allocated to this project. Pertinent toxlcologlc
and environmental data were located through on-Hne literature searches of
the Chemical Abstracts, TOXLINE, CANCERLINE and the CHEMFATE/CATALOG data
bases. The basic literature searched supporting this document 1s current up
to September, 1984. Secondary sources of Information have also been relied
upon 1n the preparation of this report and represent large-scale health
assessment efforts that entail extensive peer and Agency review. The
following Office of Health and Environmental Assessment (OHEA) sources have
been extensively utilized:
U.S. EPA. 1980b. Ambient Water Quality Criteria for Pentachloro-
phenol. Environmental Criteria and Assessment Office, Cincinnati,
OH. EPA 440/5-80-065. NTIS PB 81-117764.
U.S. EPA. 1985. Drinking Water Criteria Document for Pentachloro-
phenol. Prepared by the Environmental Criteria and Assessment
Office, Cincinnati, OH, OHEA for the Office of Drinking Water,
Washington, DC. Final draft.
The Intent 1n these assessments 1s to suggest acceptable exposure levels
whenever sufficient data were available. Values were not derived or larger
uncertainty factors were employed when the variable data were limited 1n
scope tending to generate conservative (I.e., protective) estimates. Never-
theless, the Interim values presented reflect the relative degree of hazard
associated with exposure or risk to the chemlcal(s) addressed.
Whenever possible, two categories of values have been estimated for sys-
temic toxicants (toxicants for which cancer 1s not the endpolnt of concern).
The first, the AIS or acceptable Intake subchronlc, 1s an estimate of an
exposure level that would not be expected to cause adverse effects when
exposure occurs during a limited time Interval (I.e., for an Interval that
does not constitute a significant portion of the Hfespan). This type of
exposure estimate has not been extensively used or rigorously defined, as
previous risk assessment efforts have been primarily directed towards
exposures from toxicants In ambient air or water where lifetime exposure Is
assumed. Animal data used for AIS estimates generally Include exposures
with durations of 30-90 days. Subchronlc human data are rarely available.
Reported exposures are usually from chronic occupational exposure situations
or from reports of acute accidental exposure.
111
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The AIC, acceptable Intake chronic, 1s similar In concept to the ADI
(acceptable dally Intake). It 1s an estimate of an exposure level that
would not be expected to cause adverse effects when exposure occurs for a
significant portion of the llfespan [see U.S. EPA (1980a) for a discussion
of this concept]. The AIC is route specific and estimates acceptable
exposure for a given route with the Implicit assumption that exposure by
other routes is Insignificant.
Composite scores (CSs) for noncarcinogens have also been calculated
where data permitted. These values are used for ranking reportable quanti-
ties; the methodology for their development is explained in U.S. EPA (1983).
For compounds for which there is sufficient evidence of carcinogenicity,
AIS and AIC values are not derived. For a discussion of risk assessment
methodology for carcinogens refer to U.S. EPA (1980a). Since cancer is a
process that is not characterized by a threshold, any exposure contributes
an Increment of risk. Consequently, derivation of AIS and AIC values would
be Inappropriate. For carcinogens, q-j*s have been computed based on oral
and inhalation data if available.
1v
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ABSTRACT
In order to place the risk assessment evaluation in proper context,
refer to the preface of this document. The preface outlines limitations
applicable to all documents of this series as well as the appropriate inter-
pretation and use of the quantitative estimates presented.
There are a number of subchronic oral animal studies which agree well
concerning the NOAEL for pentachlorophenol. Although fetotoxicity has been
associated with pentachlorophenol exposure, the NOAEL for this endpoint
appears to be in the same range as the NOAEL for liver damage in adult
animals. The sole chronic study suggests the same effect level as the
subchronic studies. Therefore, the estimated oral AIS and AIC are both 2.1
mg/day. A CS of 20 was derived based on fetal toxicity in rats exposed
orally during the reproductive period.
There are no adequate data concerning inhalation exposure to this
compound.
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ACKNOWLEDGEMENTS
The Initial draft of this report was prepared by Syracuse Research
Corporation under Contract No. 68-03-3112 for EPA's Environmental Criteria
and Assessment Office, Cincinnati, OH. Dr. Christopher OeRosa and Karen
Blackburn were the Technical Project Monitors and Helen Ball was the Project
Officer. The final documents In this series were prepared for the Office of
Emergency and Remedial Response, Washington, DC.
Scientists from the following U.S. EPA offices provided review comments
for this document series:
Environmental Criteria and Assessment Office, Cincinnati, OH
Carcinogen Assessment Group
Office of A1r Quality Planning and Standards
Office of Solid Waste
Office of Toxic Substances
Office of Drinking Water
Editorial review for the document series was provided by:
Judith Olsen and Erma Durden
Environmental Criteria and Assessment Office
Cincinnati, OH
Technical support services for the document series was provided by:
Bette Zwayer, Pat Daunt, Karen Mann and Jacky Bohanon
Environmental Criteria and Assessment Office
Cincinnati, OH
v1
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TABLE OF CONTENTS
Page
1. ENVIRONMENTAL CHEMISTRY AND FATE 1
2. ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS 3
2.1. ORAL 3
2.2. INHALATION 3
3. TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS 4
3.1. SUBCHRONIC 4
3.1.1. Oral 4
3.1.2. Inhalation 6
3.2. CHRONIC.
3.2.1. Oral 6
3.2.2. Inhalation 6
3.3. TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS.
3.4.
3.3.1. Oral
3.3.2. Inhalation
TOXICANT INTERACTIONS
4. CARCINOGENICITY
4.1.
4.2.
4.3.
4.4.
5. REGUU
HUMAN DATA
4.1.1. Oral
4.1.2. Inhalation
BIOASSAYS
4.2.1. Oral
4.2.2. Inhalation
OTHER RELEVANT DATA
WEIGHT OF EVIDENCE
VTORY STANDARDS AND CRITERIA
6
8
8
Q
9
9
9
9
9
9
, 9
10
11
vli
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TABLE OF CONTENTS (cont.)
Page
6. RISK ASSESSMENT 12
6.1. SUBCHRONIC EXPOSURE (AIS) 12
6.1.1. Oral 12
6.1.2. Inhalation 12
6.2. CHRONIC EXPOSURE (AIC) 12
6.2.1. Oral 12
6.2.2. Inhalation 13
6.3. CARCINOGENIC-POTENCY (q-[*) 13
6.3.1. Oral 13
6.3.2. Inhalation 13
7. REFERENCES 14
APPENDIX: Summary Table for Pentachlorophenol 22
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LIST OF ABBREVIATIONS
ADI Acceptable dally Intake
AIC Acceptable Intake chronic
AIS Acceptable Intake subchronlc
BCF Bloconcentratlon factor
bw Body weight
CAS Chemical abstract service
CS Composite score
GI Gastrointestinal
LOAEL Lowest-observed-adverse-effect level
MED Minimum effective dose
NOAEL No-observed-adverse-effect level
NOEL No-observed-effect level
ppm Parts per million
RVd Dose-rating value
RVe Effect-rating value
SGPT Serum glutamlc pyruvlc transamlnase
STEL Short-term exposure limit
TLV Threshold limit value
TWA Time-weighted average
1x
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1. ENVIRONMENTAL CHEMISTRY AND FATE
The relevant physical and chemical properties and environmental fate of
pentachlorophenol (PCP) (CAS No. 87-86-5) are as follows:
Chemical class: polychlorlnated phenol
Molecular weight: 266.35
Vapor pressure at 20°C: l.lxKT4 mm Hg (Verschueren, 1983)
Water solubility at 20°C: 14 mg/a. (Verschueren, 1983)
Log octanol/water 5.01
partition coefficient: (Verschueren, 1983)
BCF: 13 In sheepshead minnow, (U.S. EPA, 1980b)
Cyprlnodon varleqatus
Half-lives 1n:
Air: unknown
Water: 14 days (Boyle et a!., 1980)
Soil: 48 days (Rao and Davidson, 1982)
A half-life value for pentachlorophenol 1n air 1s not available.
Assuming a first order reaction, and using the equation
LN ^ = R] x T,
where:
A = Initial concentration
X = concentration at time "T"
R. = rate constant,
photodecomposltlon half-lives of 2.2 days and 32 days may be calculated from
the data on the Irradiation of pentachlorophenol with light of wavelengths
>290 nm when the compound was adsorbed on silica gel and coated on glass
plates, respectively (Korte et al., 1978).
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The mobility of pentachlorophenol 1n soil 1s not known with certainty.
It has been reported that pentachlorophenol sorptlon 1n soils 1s dependent
on soil pH and organic matter content. In organic-rich acidic soils, penta-
chlorophenol 1s likely to be sorbed strongly (U.S. EPA, 1985). Conversely,
pentachlorophenol may leach from soils having neutral or basic pH and low
organic matter content.
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2. ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS
2.1. ORAL
The available studies Indicate that pentachlorophenol 1s absorbed
rapidly from the 61 tract. Rats exposed to pentachlorophenol either In the
diet {350 ppm) or 1n drinking water (-32 mg/S. as sodium pentachlorophenol)
had plasma concentrations of 30+3 and 40^8 ymol/8. pentachlorophenol,
respectively, after 7 days of exposure (Meerman et al., 1980). Braun and
Sauerhoff (1976) reported that the average half-time for 61 absorption of
pentachlorophenol 1n monkeys was 2.7 hours. Braun et al. (1978) reported
that the average half-time for absorption of pentachlorophenol 1n human vol-
unteers was 1.3+0.4 hours, following administration of a single dose (0.1
mg/kg bw). Braun et al. (1977) also reported on the absorption of penta-
chlorophenol 1n rats. Following administration of a single oral dose of 10
mg PCP/kg bw, peak plasma levels of pentachlorophenol were reported to be 45
ppm for both males and females 8-12 hours post-treatment.
2.2. INHALATION
Casarett et al. (1969) demonstrated that pentachlorophenol 1s readily
absorbed by Inhalation. Workers exposed to pentachlorophenol 1n a wood-
treating plant 1n Honolulu were found to have pentachlorophenol 1n their
urine. In order to determine the possibility of pentachlorophenol absorp-
tion by Inhalation, two workers spent 45 minutes 1n an enclosed process area
resulting 1n mean urinary concentrations of pentachlorophenol equal to 230
ng/9. and 432 ng/8. for the first and second worker, respectively. Based
on respiratory rates, estimated tidal volume and pentachlorophenol recovery
1n the urine, absorption of pentachlorophenol by these two men was estimated
to be 88 and 76%, respectively, of the estimated Inhaled dose.
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3. TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS
3.1. SUBCHRONIC
Ep1dem1olog1cal studies have revealed a variety of adverse effects due
to occupational exposure to pentachlorophenol, but the routes of exposure
(dermal, oral, Inhalation) cannot be separated. These effects Include serum
enzyme Induction (Klemmer, 1972), Increased Incidences of low-grade Infec-
tions and Inflammation (Klemmer et a!., 1980) and depressed kidney function,
which may be partially reversible (Begley et a!., 1977).
3.1.1. Oral. Several studies of the subchronlc 'oral toxldty of penta-
chlorophenol 1n experimental animals are summarized 1n Table 3-1. Oelchmann
et al. (1942) exposed rats, cats and rabbits to pentachlorophenol either 1n
the diet or by gavage, but the purity of the pentachlorophenol was unspeci-
fied, and the number of animals observed was small. Also, a number of
Investigators have found that technical grade pentachlorophenol, contam-
inated with d1benzo-p_-d1ox1ns, produced effects 1n rats (following sub-
chronic exposure) that were not seen 1n parallel experiments where pure
pentachlorophenol was used (Johnson et al., 1973; Goldstein et al., 1977;
Kerkvllet et al., 1982a,b). The remaining studies summarized 1n Table 3-1
used "pure" pentachlorophenol.
NOELs of 3 mg/kg bw/day and 100 ppm are derived from the rat studies of
Johnson et al. (1973) and Goldstein et al. (1977), respectively. Given an
average rat weight of 300 g and assuming a dally food consumption of 5% of
Us body weight, 100 ppm may be adjusted to 5 mg/kg bw/day.
A LOAEL of 50 ppm based on liver lesions might be established from the
Kerkvllet et al. (1982a,b) study on mice (number of animals was not speci-
fied). Assuming an average food Intake of 13% of the body weight/day, the
50 ppm dietary concentration may be adjusted to 6.5 mg/kg bw/day.
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TABLE 3-1
Subchronlc Toxlclty of Orally Administered Pentachlorophenol
i
in
i
Species
Rat
Number
10/group
588
300
ppm
ppm
Dose
in diet
In diet
Duration
26 weeks
28 weeks
No
In
Effects
gross signs of toxlclty.
food consumption and body
Decreases
weight at
I
Reference
Delchmann et al..
1942
Rat NR 0, 3, 10 or 30 mg
pure PCP/kg bw/day
Rat 6/group 0. 20, 100, 500 ppm
pure PCP In the diet
House NR 0, 50 or 500 pure PCP
ppm In the diet
both doses. Unspecified htstologlcal
abnormalities.
90 days Increased liver weight at 10 and 30
mg/kg. Increased kidney weight at
30 mg/kg.
8 months At 500 ppm: Increased glucuronyl trans-
ferase to aryl hydrocarbon hydroxylase
activities; reduction In body weight.
10-12 weeks Lesions In the liver at both doses.
Dose-related Induction of splenic
tumor development following HSV/MSB
challenge.*
Johnson et al., 1973
Goldstein et al., 1977
Klrkvllet et al., 1982a,b
Rabbit
Rabbit
Cat
Pig
5 35 mg/kg bw by gavage
raised from 35-200
mg/kg bw
23 3 mg/kg bw by gavage
4 1.25 or 2.5 mg/kg bw
4/group 0, 5, 10 or 15 mg
pure PCP/kg bw/day
15 days at
35 mg/kg bw;
19 days after
day 15 dose of
35 mg/kg bw
6 days/week
for 15 weeks
10 weeks
30 days
Death upon Ingest Ion of a total of
190-390 mg/kg bw.
No effect.
No effect.
10 and 15 mg/kg/day: Increased liver
weights. Unspecified dose: diffuse.
cloudy swelling of the hepatocytes.
No hlstopathologlcal changes In the
liver, kidney, spleen, brain and
muscles. No effect on body weight or
blood chemistry.
Delchmann et al., 1942
Delchmann et al., 1942
Delchmann et al.. 1942
Grelchus et al.. 1979
'Assessment of the Immune system
NR = Not reported
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3.1.2. Inhalation. Pertinent data regarding subchronlc Inhalation expo-
sure to pentachlorophenol could not be located 1n the available literature.
3.2. CHRONIC
3.2.1. Oral. Only one chronic study regarding oral exposure to penta-
chlorophenol was located 1n the available literature. Schwetz et al. (1978)
exposed groups of 27 male and 27 female rats to 0, 1, 3, 10 or 30 mg purl-
fled pentachlorophenol/kg bw/day for either 22 months (males) or 24 months
(females). During the study, body weight, food consumption and general
behavior were recorded on a monthly basis. Upon termination of the study,
endpolnts observed Included gross and microscopic pathology, organ weights,
hematologlcal and urologlcal variables and clinical chemistry. At the 30
mg/kg/day level of treatment, a reduced rate of body weight gain and
Increased specific gravity of the urine were observed 1n females. Further-
more, both sexes had Increased SGPT enzyme activity at this level of expo-
sure. Pigmentation of the Hver and kidneys was observed 1n females exposed
to 10 or 30 mg/kg/day, and In males exposed to 30 mg/kg/day. The 3 mg/kg
bw/day level of exposure thus represents a chronic NOEL.
3.2.2. Inhalation. Pertinent data regarding chronic exposure to penta-
chlorophenol by Inhalation could not be located 1n the available literature.
3.3. TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS
3.3.1. Oral. A number of studies that have Investigated the teratogenl-
clty of orally administered pentachlorophenol 1n rodents are summarized 1n
Table 3-2 (Larsen et al., 1975; Schwetz and Gehrlng, 1973; Schwetz et al.,
1974a,b, 1978; Hlnkle, 1973). Although these studies failed to demonstrate
teratogenlclty, fetotoxlc effects associated with delayed
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TABLE 3-2
Teratogenlclty of Orally Administered Pentachlorophenol
Strain/Species
CD rats
No. Dams
6/group
Dose
0 or 60
mg/kg bw
Vehicle
pure PCP
by gavage
Days Administered
single dose on day
8, 9, 10, 11, 12 or
Effects
Three of four malformations were
seen when pentachlorophenol was
Reference
Larsen et al.,
1975
Sprague-Dawley
rats
Sprague-Dawley
rats
NR
20/group
Golden Syrian
hamsters
NR
0-50 mg/kg
bw/day
0, 3 or
mg/kg
bw/day
30
NR
diet
1.25-20
mg/kg
bw/day
NR
13 of gestation
dally doses on day
6-15, 11-12 or 15
of gestation
62 days prior to
mating, throughout
gestation to
lactation
days 5-10 of
gestation
administered on day 9 of gestation.
Treatment on day 9 or 10 resulted
In significant reduction In fetal
weight gain. The authors concluded
that the malformations could have
resulted from maternal toxlclty.
Dose-related fetotoxlclty with a
LOAEL at 5 mg/kg bw/day.
No effect at 0 or 3 mg/kg bw/day.
30 mg/kg bw/day: Significant reduc-
tion In neonatal body weight; de-
creased percent survival of pups
and decreased percent live births.
Increase In lumbar spurs and ver-
tebrae with unfused centra were
attributed to fetotoxlclty.
This dose also resulted In maternal
toxlclty.
Increase In fetal deaths and/or
resorpttons In 3 of 6 groups tested.
No other details In the abstract.
Schwetz and
Gehrlng. 1973;
Schwetz et al.,
1974a,b
Schwetz et al.,
1978
Hlnkle. 1973
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skeletal ossification were observed. Schwetz et a"). (1974a,b) and Schwetz
and Gehrlng (1973) reported a dose-related fetotoxIcHy with a LOAEL of 5 mg
pentachlorophenol/kg bw/day. A NOEL of 3 mg/kg bw/day was established from
the study of Schwetz et al. (1978), In which 10 male and 20 female Sprague-
Dawley rats were fed pentachlorophenol 62 days prior to mating and through-
out gestation and lactation. Fetotoxlc effects as well as maternal toxldty
were seen at a level of 30 mg pentachlorophenol/kg bw/day. Since penta-
chlorophenol apparently does not cross the placental barrier, the observed
fetotoxlclty may be a reflection of maternal toxldty (Larsen et al., 1975).
3.3.2. Inhalation. Pertinent data regarding the teratogenlcity of
Inhaled pentachlorophenol could not be located In the available literature.
3.4. TOXICANT INTERACTIONS
A recent study (Boberg et al., 1983) Indicates that pentachlorophenol
antagonizes the tumorlgenlc effects of either 1'-hydroxysafrole or Us
metabolite, 1'-sulfooxysafrole, 1n mouse liver. In addition, pentachlor-
ophenol 1s known to reduce the toxldty of N-hydroxy-2-acetylam1nofluorene
(Meerman et al., 1980; Meerman and Mulder, 1981). In both cases the antag-
onistic effects of pentachlorophenol were reported to be due to Inhibition
of cytosollc sulfotransferase.
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4. CARCINOGENICITY
4.1. HUMAN DATA
4.1.1. Oral. Pertinent data regarding the cardnogenlcHy to humans of
Ingested pentachlorophenol could not be located In the available literature.
4.1.2. Inhalation. Pertinent data regarding the cardnogenlcHy to
humans of Inhaled pentachlorophenol could not be located 1n the available
literature.
4.2. BIOASSAYS
The NTP (1983) 1s currently testing technical grade pentachlorophenol
and Dowlclde EC-7 (pentachlorophenol) for carcinogenic activity. However,
results from these studies are not yet available.
4.2.1. Oral. Two studies demonstrated that pentachlorophenol was not
carcinogenic when administered orally. Blonetlcs Research Laboratories
(BRL, 1968) administered 46.4 mg pentachlorophenol/kg bw/day by gavage from
days 7-28 postpartum to two strains [(C57B1/6 x C3H/Anf)F and (C57B1/6 x
AKR)F,j of male and female mice (18/sex/straln). At 28 days postpartum,
the mice were transferred to diets containing 130 ppm for 78 weeks. No
significant Increase 1n the Incidence of tumors was seen In the treated
animals relative to sham-treated controls (79-90 mlce/sex/straln).
Schwetz et al. (1978) exposed groups of 27 male and 27 female Sprague-
Dawley rats orally to 0, 1, 3, 10 or 30 mg pentachlorophenol/kg bw/day for
22-24 months. No significant Increase In the numbers or types of tumors was
observed In the treated animals compared with controls.
4.2.2. Inhalation. Pertinent data regarding the cardnogenlcHy of
Inhaled pentachlorophenol could not be located 1n the available literature.
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4.3. OTHER RELEVANT DATA
Pentachlorophenol was not found to be mutagenlc In Salmonella typhl-
murlum. Escherlchla coll or Serratl.a marcescens. regardless of the presence
or absence of mammalian S-9 liver preparations (Andersen et a!., 1972;
Simmon et al., 1977; Lemma and Ames, 1975; Morlya et al., 1983; Waters et
a!., 1982; Buselmaler et al., 1973; Fahrig, 1974). However, positive
results were obtained by Shlrasu (1976) and Waters et al. (1982) for
Bacillus subtnis. Fahrig (1974) reported that pentachlorophenol produced a
slight Increase 1n chromosomal aberrations In cultured human lymphocytes,
but there 1s some question as to whether the Increase Is statistically
significant. In an in vitro study, Wyllle et al. (1975) reported that no
statistically significant differences 1n chromosomal aberrations were seen
between workers exposed to airborne pentachlorophenol (263-1887 ng/m3) and
their controls. In contrast, Bauchlnger et al. (1982) observed a slight but
significant Increase 1n the number of chromosomal aberrations 1n the periph-
eral lymphocytes of workers exposed to sodium pentachlorophenol (mean blood
concentration = 4.73^3.41 yg/ms.) or pentachlorophenol (mean blood
concentration = 2.23+1.51 yg/ma) with respect to controls.
4.4. ' WEIGHT OF EVIDENCE
Based upon the criteria for evaluating the weight of evidence of the
cardnogenldty of chemicals for humans proposed by the Carcinogen Assess-
ment Group of the U.S. EPA (Federal Register, 1984), there appear to be no
data regarding the cardnogenldty of pentachlorophenol In humans, rats or
mice. Pentachlorophenol 1s most appropriately classified 1n Group E - No
Evidence of Cardnogenldty for Humans.
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5. REGULATORY STANDARDS AND CRITERIA
The U.S. EPA (19805) established an Interim ADI of 2.1 mg/man/day for
Ingestlon of pentachlorophenol. This was based on a NOAEL of 3 mg/kg
derived from the study of Schwetz et al. (1978) on rats (discussed 1n Sec-
tion 3.2.1.). Since the odor threshold for pentachlorophenol 1s lower than
the Interim ADI, however, the U.S. EPA (1980b) established a criterion level
of 30 vg/s. for pentachlorophenol In water to protect the population from
underslrable organoleptlc characteristics.
The AC6IH (1983) has established a TLV-TWA of 0.5 mg/m3 and a STEL of
1.5 mg/m3 for occupational exposure to pentachlorophenol, with the nota-
tion that dermal absorption may contribute to overall exposure. Since
chronic exposure to pentachlorophenol does not seem to produce cumulative
effects, these values were chosen by analogy to similar chemicals and were
Intended to protect from the vascular Injury seen upon acute exposure to
pentachlorophenol.
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6. RISK ASSESSMENT
6.1. ACCEPTABLE INTAKE SUBCHRONIC (AIS)
6.1.1. Oral. Several effect levels that could be used in risk assessment
were defined 1n Section 3.1.1. A NOAEL of 10 mg/kg bw/day based on In-
creased liver weight was established from the study of Johnson et al.
(1973), though the numbers of animals treated were not reported. NOELs of 5
mg/kg bw/day and 3 mg/kg bw/day 1n rats were derived from the subchronic
toxldty study of Goldstein et al. (1977) and the subchronic teratogenicity
study of Schwetz et al. (1978), respectively. Schwetz et al. (1974a,b) and
Schwetz and Gehring (1973) reported a LOAEL of 5 mg/kg bw/day for fetotoxic-
1ty in rats exposed to pentachlorophenol during gestation. Since 3 mg/kg
bw/day 1s the highest NOEL, which 1s lower than the LOAEL for fetotoxlclty,
this value will be used in the calculation of an AIS.
Dividing 3 mg/kg bw/day by an uncertainty factor of 100 (10 to account
for the range of sensitivities in the human population; 10 for extrapolating
from animals to humans) establishes an Interim ADI of 0.03 mg/kg bw/day for
subchronic Ingestion of pentachlorophenol. Assuming that an average man
weighs 70 kg, this AIS 1s equivalent to 2.1 mg/man/day.
6.1.2. Inhalation. The lack of pertinent data regarding subchronic
inhalation of pentachlorophenol precludes quantitative assessment of risk
due to exposure. It 1s not appropriate to derive an AIS from the TLV estab-
lished by ACGIH (1983), since the value was derived by analogy to chemicals
similar to pentachlorophenol.
6.2. ACCEPTABLE INTAKE CHRONIC (AIC)
6.2.1. Oral. A NOEL of 3 mg/kg bw/day can be derived from the chronic
study of Schwetz et al. (1978) on rats. Dividing 3 mg/kg bw/day by an un-
certainty factor of 100 (10 for extrapolating from animals to humans; 10
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to account for the range of sensitivities 1n the human population) estab-
lishes an AIC of 0.03 mg/kg bw/day for chronic Ingestlon of pentachlorophe-
nol. Assuming that an average man weighs 70 kg, this AIC 1s equivalent to
2.1 mg/man/day. This value 1s 1n perfect agreement with that established by
the U.S. EPA (1980b). U.S. EPA (1984) calculated a CS for the effects of
fetal toxldty observed by Schwetz et al. (1978) 1n rats fed diets that
provided 30 mg/kg/ day for 110 days of the reproductive period. The animal
dose (30 mg/kg/day) was converted to a human MED by dividing by a factor of
10 to extrapolate from subchronlc to chronic exposure and multiplying by 70,
the assumed body weight of an average human, to express the result as
mg/day. The result, 210 mg/day, corresponds to an RV of 2.0. The fetal
toxldty observed Is assigned an RV of 10. A CS of 20, the product of
RV. and RV , 1s calculated.
d e
6.2.2. Inhalation. The lack of pertinent data regarding chronic Inhala-
tion of pentachlorophenol precludes quantitative assessment of risk due to
exposure.
6.3. UNIT CARCINOGENIC RISK (q^)
6.3.1. Oral. The carcinogenic risk associated with Ingestlon of penta-
chlorophenol cannot be quantified, since the only studies to date (BRL,
1968; Schwetz et al., 1978) have yielded negative results.
6.3.2. Inhalation. The lack of pertinent data regarding the carclnogenl-
dty of Inhaled pentachlorophenol precludes assessment of carcinogenic risk.
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7. REFERENCES
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Hlnkle, O.K. 1973. Fetotoxlc effects of pentachlorophenol on the Golden
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U.S. EPA. 1985. Drinking Water Criteria Document for Pentachlorophenol.
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O r\) ;o C
zr oo CD -.-
-• O TO C^
APPENDIX
Summary Table for Penlachlorophenol
Species
Inhalation
AIS
AIC
Oral
AIS rat
AIC rat
Maximum
composite rat
score
Experimental Effect Acceptable Intake Reference
Dose/Exposure (AIS or AIC}
ND
ND
NOEL = 3 mg/kg bw/day none 2.1 mg/man/day Schwetz et al., 1978
NOEL = 3 mg/kg bw/day none 2.1 mg/man/day Schwetz et al.. 1378
30 mg/kg/day for 110 fetal 20 Schwetz et al., 1978;
days of reproductive toxlclty U.S. EPA, 1984
period (RVd = 2.0) (RVe =- 10)
ND ^ Not derived
o
a
>
era
3
o
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