United States Office of Water EPA 440/5-80-065
Environmental Protection Regulations and Standards October 1980
Agency Criteria and Standards Division .
Washington DC 20460 £* . /
oEPA Ambient
Water Quality
Criteria for
Pentachlorophenol
-------
AMBIENT WATER QUALITY CRITERIA FOR
PENTACHLOROPHENOL
Prepared By
U.S. ENVIRONMENTAL PROTECTION AGENCY
Office of Water Regulations and Standards
Criteria and Standards Division
Washington, D.C.
Office of Research and Development
Environmental Criteria and Assessment Office
Cincinnati, Ohio
Carcinogen Assessment Group
Washington, D.C.
Environmental Research Laboratories
Corvaljis, Oregon
Duluth, Minnesota
Gulf Breeze, Florida
Narragansett, Rhode Island
-------
DISCLAIMER
This report has been reviewed by the Environmental Criteria and
Assessment Office, U.S. Environmental Protection Agency, and approved
for publication. Mention of trade names or commercial products does not
constitute endorsement or recommendation for use.
AVAILABILITY NOTICE
This document is available to the public through the National
Technical Information Service, (NTIS), Springfield, Virginia 22161.
ii
-------
FOREWORD
Section 304 (a)(l) of the Clean Water Act of 1977 (P.L. 95-217),
requires the Administrator of the Environmental Protection Agency to
publish criteria for water quality accurately reflecting the latest
scientific knowledge on the kind and extent of all identifiable effects
on health and welfare which may be expected from the presence of
pollutants in any body of water, including ground water. Proposed water
quality criteria for the 65 toxic pollutants listed under section 307
(a)(l) of the Clean Water Act were developed and a notice of their
availability was published for public comment on March 15, 1979 (44 FR
15926), July 25, 1979 (44 FR 43660), and October 1, 1979 (44 FR 56628).
This document is a revision of those proposed criteria based upon a
consideration of comments received from other Federal Agencies, State
agencies, special interest groups, and individual scientists. The
criteria contained in this document replace any previously published EPA
criteria for the 65 pollutants. This criterion document is also
published in satisifaction of paragraph 11 of the Settlement Agreement
in Natural Resources Defense Council, et. al. vs. Train, 8 ERC 2120
(D.D.C. 1976), modified, 12 ERC 1833 (D.D.C. 1979).
The term "water quality criteria" is used in two sections of the
Clean Water Act, section 304 (a)(l) and section 303 (c)(2). The term has
a different program impact in each section. In section 304, the term
represents a non-regulatory, scientific assessment of ecological ef-
fects. The criteria presented in this publication are such scientific
assessments. Such water quality criteria associated with specific
stream uses when adopted as State water quality standards under section
303 become enforceable maximum acceptable levels of a pollutant in
ambient waters. The water quality criteria adopted in the State water
quality standards could have the same numerical limits as the criteria
developed under section 304. However, in many situations States may want
to adjust water quality criteria developed under section 304 to reflect
local environmental conditions and human exposure patterns before
incorporation into water quality standards. It is not until their
adoption as part of the State water quality standards that the criteria
become regulatory.
Guidelines to assist the States in the modification of criteria
presented in this document, in the development of water quality
standards, and in other water-related programs of this Agency, are being
developed by EPA.
STEVEN SCHATZOW
Deputy Assistant Administrator
Office of Water Regulations and Standards
111
-------
ACKNOWLEDGEMENTS
Aquatic Life Toxicology:
Gary A. Chapman, ERL-Corvalis
U.S. Environmental Protection Agency
David J. Hansen, ERL-Gulf Breeze
U.S. Environmental Protection Agency
Mammalian Toxicology and Human Health Effects:
Gary Van Gelder (author)
University of Missouri
John F. Risher (doc. mgr.) ECAO-Cin
U.S. Environmental Protection Agency
Bonnie Smith (doc. mgr.) ECAO-Cin
U.S. Environmental Protection Agency
Joyce Goldstein
National Institute for Environmental
Health Sciences
Van Kozak
University of Wisconsin
Si Duk Lee, ECAO-Cin
U.S. Environmental Protection Agency
Gary D. Osweiler
University of Missouri
Philip J. Wirdzek, OWPS
U.S. Environmental Protection Agency
Robert M. Bruce, ECAO-RTP
U.S. Environmental Protection Agency
Patrick J. Durkin
Syracuse Research Corporation
William Dykstra
U.S. Environmental Protection Agency
Rolf Hartung
University of Michigan
N.E. Kowal, HERL
U.S. Environmental Protection Agency
Steven D. Lutkenhoff, ECAO-Cin
U.S. Environmental Protection Agency
Jerry F. Stara, ECAO-Cin
U.S. Environmental Protection Agency
Technical Support Services Staff: D.J. Reisman, M.A. Garlough, B.L. Zwayer,
P.A. Daunt, K.S. Edwards, T.A. Scandura, A.T. Pressley, C.A. Cooper,
M.M. Denessen.
Clerical Staff: C.A. Haynes, S.J. Faehr, L.A. Wade, D. Jones, B.J. Bordicks,
B.J. Quesnell, P. Gray, R. Rubinstein.
-------
TABLE OF CONTENTS
Criteria Summary
Introduction A-l
Aquatic Life Toxicology B-l
Introduction B-l
Effects B-3
Acute Toxicity B-3
Chronic Toxicity B-5
Plant Effects B-6
Residues B-7
Miscellaneous B-8
Summary B-9
Criteria B-10
References B-29
Mammalian Toxicology and Human Health Effects C-l
Introduction C-l
Exposure C-2
Ingestion from Water and Food C-2
Inhalation C-4
Dermal C-9
Pharmacokinetics C-12
Absorption C-12
Distribution C-14
Metabolism C-17
Excretion C-17
Effects C-20
Acute, Subacute, and Chronic Toxicity C-20
Teratogenicity C-27
Mutagenicity C-29
Carcinogenicity C-30
Other Effects C-32
Criterion Formulation C-34
Existing Guidelines and Standards C-34
Current Levels of Exposure C-34
Special Groups at Risk C-35
Basis and Derivation of Criterion C-36
References C-40
-------
CRITERIA DOCUMENT
PENTACHLOROPHENOL
CRITERIA
Aquatic Life
The available data for pentachlorophenol indicate that acute
and chronic toxicity to freshwater aquatic life occurs at concen-
trations as low as 55 and 3.2 pg/1, respectively, and would occur
at lower concentrations among species that are more sensitive than
those tested.
The available data for pentachloroohenol indicate that acute
and chronic toxicity to saltwater aquatic life occur at concentra-
tions as low as 53 and 34 yg/1, respectively, and would occur at
lower concentrations among species that are more sensitive than
those tested.
Human Health
For comparison purposes, two approaches were used to derive
criterion levels for pentachlorophenol. Based on available toxic-
ity data, for the protection of public health, the derived level is
1.01 mg/1. Using available organoleptic data, for controlling
undesirable taste and odor qualities of ambient water, the estimat-
ed level is 30 yg/1. It should be recognized that organoleptic
data as a basis for establishing a water quality criterion have
limitations and have no demonstrated relationship to potential
adverse human health effects.
VI
-------
INTRODUCTION
Pentachlorophenol (PCP) is a commercially produced bacteri-
cide, fungicide, and slimicide used primarily for the preservation
of wood, wood products, and other materials. As a chlorinated
hydrocarbon, its biological properties have also resulted in its
use as an herbicide, insecticide, and molluscicide.
Pentachlorophenol is prepared by the chlorination of phenol in
the presence of a catalyst. PCP has the empirical formula CgClcOH,
a molecular weight of 266.35, a density of 1.978, and a vapor pres-
sure of 0.12 mm Hg at 100°C (Stecher, 1968; Natl. Fire Prot.
Assoc., 1973; Sax, 1975; Spector, 1956). The melting point of pen-
tachlorophenol ranges between 190 and 191°C for the anhydrous form
(Stecher, 1968; Weast, 1975). PCP decomposes at its boiling point
of 309 to 310°C (Stecher, 1968).
PCP is slightly soluble in water (14 mg/1 at 20°C), while its
alkaline salts, such as sodium pentachlorophenate (Na-PCP), are
highly soluble in water (Weast, 1975). The log of the octanol/
water partition coefficient is 5.01 (Leo, et al. 1971).
It has been shown that commercial preparations of PCP contain
certain "caustic insolubles" or "nonphenolic, neutral impurities,"
such as tetra-, penta-, hexa-, hepta-, and octachlorodibenzofurans
and the octachlorodibenzo-p-dioxins (Johnson, et al. 1973), as well
as hexachlorobenzene and hexachlorodibenzo-p-dioxin (Schwetz, et
al. 1978). The chemically pure PCP used in comparative studies had
no detectable concentrations of any chlorinated dioxins.
A-l
-------
PCP is known to undergo photochemical degradation in solution
in the presence of sunlight, with the subsequent formation of sev-
eral chlorinated benzoquinones, 2,4,5,6-tetrachlororesorcinol, and
chloranilic acid (Mitchell, 1961; Hanadmad, 1967) . Na-PCP is de-
composed directly by sunlight, with the formation of numerous prod-
ucts, including oxidized monomers, dimers, a trimer, and chlorani-
lic acid (Munakata and Kuwahara, 1969; Haitt, et al. 1960). Wong
and Crosby (1977) reported the degradation by sunlight or ultravio-
let light of dilute solutions of pentachlorophenol to lower chloro-
phenols, tetrachlorodihydroxybenzen.es, and nonaromatic fragments,
such as dichloromaleic acid. The irradiation of Na-PCP in rela-
tively high concentrations in aqueous solutions has been reported
to form octachlorodibenzo-p-dioxin (Wong and Crosby, 1977).
Although PCP and Na-PCP are disseminated^in the environment,
there is a paucity of data on their environmental concentration,
fate, and effects. Their principal use as a wood preservative re-
sults in point source water contamination at both manufacturing and
wood preservation sites and, conceivably, non-point source water
contamination through runoff wherever there are PCP-treated lumber
products exposing PCP or Na-PCP to soil. Harvey and Crafts (1952)
noted that PCP persisted in warm, moist soils for a period of 12
months.
A-2
-------
REFERENCES
Haitt, C.W., et al. 1960. The action of sunshine on sodium oenta-
chlorophenate. Am. Jour. Trop. Med. Hyg. 9: 527.
Hanadmad, N. 1967. Photolysis of pentachloronitrobenzene,
2,3,5,6-tetrachloronitrobenzene and pentachlorophenol. Ph.D.
dissertation. University of California, Davis.
Harvey, w.A. and A.S. Crafts. 1952. Toxicity of pentachlorophenol
and its sodium salt in three yolo soils. Hilgardia. 21: 487.
Johnson, R.L., et al. 1973. Chlorinated dibenzodioxins and penta-
chlorophenol. Environ. Health. Perspect. 5: 171.
Leo, A., et al. 1971. Partition coefficients and their uses.
Chem. Rev. 7: 525.
Mitchell, L.C. 1961. Effect of ultraviolet light (2537A) on 141
pesticide chemicals by paper chromatography. Jour. Off. Anal.
Chem. 44: 643.
Munakata, K. and M. Kuwahara. 1969. Photochemical degradation
products of pentachlorophenol. Residue Rev. 25: 13.
National Fire Protection Assoc. 1973. Fire protection guirie on
hazardous materials. 5th ed. Boston.
A-3
-------
Sax, N.I. 1975. Dangerous Properties of Industrial Materials.
4th ed. Van Nostrand Reinhold Co., New York.
Schwetz, B.A., et al. 1978. Results of Two-year Toxicity and Re-
production Studies on Pentachlorophenol in Rats. In; K.R. Rao
(ed.), Pentachlorophenol: Chemistry, Pharmacology, and Environ-
mental Toxicology. Plenum Press, New York. p. 301.
Spector, U.S. 1956. Handbook of Toxicology. W.B. Saunders Co.,
Philadelphia.
Stecher, P.G. (ed.) 1968. The Merck Index. 8th ed. Merck and
Co., Inc., Rahway, New Jersey.
Weast, R.C. (ed.) 1975. Handbook of Chemistry and Physics. 5th
ed. CRC Press, Cleveland, Ohio.
Wong, A.S. and D.G. Crosby. 1977. Photodecomposition of penta-
chlorophenol (PCP). Proc. Symp. on Pentachlorophenol, June 27-29.
U.S. Environ. Prot. Agency and Univ. West Florida.
A-4
-------
Aquatic Life Toxicology*
INTRODUCTION
Pentachlorophenol (PCP) is one of the most widely used pesticides in
the United States. Commonly available as either the phenol or its sodium
phenate salt, PCP is used as an algicide, bactericide, fungicide, herbicide,
molluscicide, and insecticide.
Prior to 1960 the high toxicity of PCP to aquatic organisms was gener-
ally recognized, but few toxicity tests had been conducted with aquatic or-
ganisms. Almost all currently available toxicity test data for PCP have
been obtained from acute tests conducted in the past 20 years, although re-
sults from several recent chronic toxicity tests and long-term growth tests
are available for assessing subacute responses. In spite of a possible high
degree of phytotoxicity, there are few studies on the toxicity of PCP to
aquatic plants. There is almost no information on the bioconcentration of
pentachlorophenol by freshwater organisms; however, bioconcentration factors
are available for a variety of saltwater organisms.
One likely reason for the paucity of chronic toxicity and freshwater
bioconcentration data is the relatively low environmental persistence of PCP
as compared to DDT and similar chlorinated hydrocarbon insecticides. Penta-
chlorophenol also appears to be rapidly excreted by fishes following forma-
tion of PCP-glucuronide and PCP-sulfate conjugates, with half-lives in tis-
sue of less than 24 hours (Lech, et al. 1978; Akitake and Kobayashi, 1975).
*The reader is referred to the Guidelines for Deriving Water Quality Cri-
teria for the Protection of Aquatic Life and Its Uses in order to better un-
derstand the following discussion and recommendation. The following tables
contain the appropriate data that were found in the literature, and at the
bottom of the appropriate table are calculations for deriving various
measures of toxicity as described in the Guidelines.
B-l
-------
Pentachlorophenol (PCP) and its sodium salt (Na-PCP) occur in a wide
variety of products that can cause contamination of the saltwater environ-
ment. Pentachlorophenol behaves as a weak acid that is readily dissociated
to form its corresponding salt in an alkaline solution (Bevenue and Beckman,
1967).
Pentachlorophenol contains variable amounts of a number of other chemi-
cals present as impurities, with the quantity of impurities greater in com-
mercial technical grade PCP than in more purified laboratory grade PCP.
Most of the impurities in PCP are lower chlorinated phenols (e.g., tetra-
and trichlorophenol) and condensation products of two chlorinated phenol
molecules (e.g., dibenzo-p-dioxins, dibenzofurans, and diphenyl ethers). At
least 19 such condensation products have been identified in various samples
of PCP (Jensen and Renberg, 1972; Firestone, et al. 1972; Plimmer, 1973;
Buser and Bosshardt, 1976).
The contribution of each or all of these impurities to the toxicity of
PCP is difficult to assess. Because of the relatively low concentrations of
impurities, any impurity would have to be several orders of magnitude more
toxic than PCP, or produce profound synergistic effects, in order to influ-
ence the toxicity of PCP appreciably. Although the lower chlorinated
phenols are unlikely to produce appreciable toxicity in this regard, the
condensation products may. The sum of the concentrations of the various
condensation products ranges from 10 to perhaps as high as 1,500 ppm in
various batches and grades of PCP.
Unless any highly toxic impurities of PCP are identified and specific-
ally addressed by aquatic life criteria, the criteria should treat PCP, in-
cluding the impurities and their toxicities, as a single entity.
If future commercial PCP is consistently shown to contain significantly
lower concentrations of toxic impurities, then the PCP toxicity data base
B-2
-------
may have to be reassessed and new data provided updating the criteria to re-
flect the changed toxicity resulting from the greater purity.
A parallel effort should be made to obtain data for aquatic and mammal-
ian species to determine the toxicity of the various chlorinated dioxins,
furans, and diphenyl ethers, for if they do contribute significantly to the
toxicity of PCP, they are likely to be toxic to aquatic organisms at ex-
tremely low concentrations.
EFFECTS
Acute Toxicity
Throughout the following aquatic life section, the convention has been
adopted to express pentachlorophenol concentrations as molecular PCP (MW
266.34) with toxicity data on other forms, e.g., Na-PCP, converted to equiv-
alent PCP concentrations.
Pentachlorophenol is reported to be acutely toxic to freshwater fish
species with 96-hour LC50 values from 34 to 600 u9/l; salmonid LC50 val-
ues ranged from 34 to 128 ug/1, and non-salmonid LC5Q values ranged from
60 to 600 ug/1 (Table 1).
Freshwater invertebrate species are poorly represented in the data
base, but standard acute toxicity tests with cladocerans produced 48-hour
EC5Q values of 240 to 800 ug/l for Daphm'a magna and 2,000 ug/1 for Daph-
nia pulex (Table 1). Acute toxicity tests with the worm, Tubifex tubifex.
yielded 24-hour LCgo values of 286 to 1,294 ug/l (Table 6). Based on
these limited data, invertebrate species appear to be about as sensitive as
non-salmonid fish species to PCP.
The wide range in PCP toxicity to Tubifex (Table 6) is apparently due
to the effects of pH, since the 24-hour LC50 values were 286, 619, and
1,294 ug/l at pH values of 7.5, 8.5, and 9.5, respectively. A similar re-
sponse was observed in the guppy, Poecilia reticulata, where the time to 50
B-3
-------
percent mortality at a single concentration (924 pg/1) was 21-38 minutes,
72-93 minutes, and 1,440 minutes at pH values of 6.0, 7.6, and 9.0, respec-
tively (Table 6).
These findings are consistent with the frequently demonstrated result
that, in aqueous solutions, molecular forms of substituted phenols are more
toxic than ionized forms. Thus, lower pH values favor the formation of mo-
lecular PCP while higher pH values favor the ionization of PCP into phenate
and hydrogen ions. Unfortunately, no data on the effects of pH on PCP tox-
icity are available from tests of longer than 24-hour duration. While it is
inadvisable to extrapolate quantitatively from these very short-term tests
to PCP toxicity in general, it is probable that PCP will be less toxic in
alkaline waters than in acidic waters.
The LCgQ values available for four saltwater invertebrate species
(Table 1) indicate that the Eastern oyster is the most sensitive, 40 ug/1
(Borthwick and Schimmel, 1978), then a polychaete worm, 435 yg/l (U.S. EPA,
1980), and least sensitive are grass shrimp and pink shrimp, 436-5,600 ug/1
(Borthwick and Schimmel, 1978; Conklin and Rao, 1978a, Bentley, et al.
1975). Studies by Conklin and Rao (1978a) indicate that the sensitivity of
grass shrimp to pentachlorophenol varies with stage of the molt cycle. In
flow-through tests, Schimmel, et al. (1978) found no significant mortality
among juvenile grass shrimp or juvenile brown shrimp after 96-hour exposures
to 515 and 195 ug/1, respectively (Table 6).
Table 1 also lists data for three species of saltwater fishes. The
96-hour LCcn values for sheepshead minnows, pinfish and striped mullet
ranged from 38 to 442 yg/1 (Borthwick and Schimmel, 1978; Parrish, et al.
1978; Schimmel, et al. 1978). No significant mortality of the longnose
killifish occurred after a 96-hour exposure to 306 ug/1 (Table 6) (Schimmel,
et al. 1978).
B-4
-------
Although the sensitivity of tested saltwater invertebrate and fish spe-
cies was very similar, pentachlorophenol appears to be most toxic to mol-
luscs (Tables 1 and 6), which is consistent with the known molluscicidal ap-
plication of PCP (Bevenue and Beckman, 1967). Most Pacific oyster embryos
developed abnormally to the straight-hinged stage when exposed to 55 yg/1
for 48 hours (Table 6) (Woelke, 1972), whereas the 48-hour EC5Q based on
abnormal embryonic development of the Eastern oyster was 40 yg/1 (Table 1)
(Borthwick and Schimmel, 1978). Also, the 192-hour EC^Q based on reduced
shell deposition in the Eastern oyster (Schimmel, et al. 1978) was 34 yq/1
(Table 6).
Chronic Toxicity
Chronic toxicity tests have been reported for two freshwater species,
the cladoceran, Daphnia magna, and the fathead minnow, and one saltwater
species, the sheepshead minnow. Chronic values were 57 and 64 yq/1 for the
fathead and sheepshead minnows, respectively, whereas the chronic value for
Daphnia magna was 240 yg/1 (Table 2).
Survival and growth were adversely affected by PCP, but reproduction
did not appear to be particularly sensitive. Adema (1978) reported 21-day
chronic mortality of Daphnia magna at 320 yg/1 but not at 180 ug/l with
PCP. Reproduction was not affected at these levels. PCP caused mortality
of sheepshead minnows at 88 ug/l, but neither growth nor fecundity was
affected at concentrations up to 195 yg/1 (Parrish, et al. 1978). With
fathead minnows, growth in an early life stage test was impaired at 73 yq/1
but not at 45 yg/1, whereas survival was adversely affected at 128 yg/1
(Holcombe, et al. manuscript).
The acute-chronic ratios for Daphnia magna, sheepshead minnow, and fat-
head minnow are 2.5, 6.9, and 3.9, respectively (Table 2).
-------
Species mean acute values and acute-chronic ratios are summarized in
Table 3.
Plant Effects
Huang and Gloyna (1968) studied the effect of PCP and 40 other sub-
stituted phenols and herbicides on chlorophyll destruction and photo-
synthesis of the alga, Chlorella pyrenoidosa. Pentachlorophenol was by far
the most toxic compound tested, producing complete destruction of chloro-
phyll in 72 hours at 7.5 yg/1 (Table 4). Since no detailed results of the
PCP test were given, it is not possible to evaluate this result fully or
determine a general dose-response relationship. Another study of PCP-in-
duced chlorosis in plants (Lemna minor) yielded a 48-hour EC™ of 800 yg/1
(Blackman, et al. 1955).
In the absence of additional freshwater plant data, it is difficult to
assess the relative sensitivity of aquatic plants and animals to PCP because
the 7.5 pg/1 plant value is lower than the lowest fish or invertebrate
96-hour LC,-0 of 34 pg/1, and the 800 pg/1 plant value is higher than any
fish or invertebrate ICf-Q except the 2,000 ug/1 48-hour ECgQ for Daphnia
pulex.
Data on the toxicity of pentachlorophenol to three species of saltwater
algae are also listed in Table 4. An EC5Q as low as 17 yg/1 for
Skeletonema costatum (U.S. EPA, 1980) indicates that pentachlorophenol may
be more toxic to some plants than to molluscs. Values for Thalassiosira
pseudonana and Dunaliella tertiolecta were as low as 179 and 170 pg/1, re-
spectively; a 12-day exposure of the alga, Monochrysis lutheri, to 293 pg/1
caused a 58 percent decrease in cell numbers (Table 6) (Woelke, 1965).
Based on the species tested, sensitivities of invertebrate, fish, and
plant species to PCP appear to be similar, and concentrations protective of
one group would be expected to protect the other groups.
B-6
-------
Residues
Reports of two freshwater studies were found which provided reasonable
assurance that steady-state levels of PCP were attained in the tissues of
freshwater organisms (Table 5). Both studies used renewed PCP concentra-
tions of 100 ug/1. The data of Kobayashi and Akitake (1975) indicated that
steady-state was attained after 96 hours and that goldfish had a whole body
bioconcentration factor of approximately 1,000. The data of Pruitt, et al.
(1977) indicated that bioconcentration was maximal after 8 days in the blue-
gill and declined thereafter. The bioconcentration factor for the muscle
was 13 after 8 days. Pentachlorophenol was rapidly lost from the body when
the fish were placed in PCP-free water.
As was true for freshwater species, steady-state bioconcentration fac-
tors for saltwater organisms were also low (390 or less) for the sheepshead
minnow (Parrish, et al. 1978) and for two molluscs, Eastern oyster
(Schimmel, et al. 1978) and blue mussel (Ernst, 1979) (Table 5). However,
pentachlorophenol in water was accumulated appreciably by the polychaete
worm, Lanice conchilega, with a bioconcentration factor of 3,830 (Ernst,
1979). A temperature range of 5 to 15°C had no discernible effect on the
bioconcentration factor of blue mussel.
Eastern oysters exposed to 25 and 2.5 ug/1 for 28 days accumulated the
chemical in their tissues to an average of 41 and 78 times, reaching
steady-state in tissues within 4 days, and when held in PCP-free water,
depurated the chemical to nondetectable concentrations in 4 days (Schimmel,
et al. 1978). Bioconcentration factors for 96-hour exposures indicate that
shrimp bioconcentrate PCP less than do fishes (Table 6). In 96-hour tests,
Schimmel, et al. (1978) determined bioconcentration factors of 1.7 for grass
shrimp and 0.26 for brown shrimp compared to 30 for longnose killifish and
38 for striped mullet.
B-7
-------
The absence of a maximum permissible tissue concentration makes it
impossible to calculate a Residue Limited Toxicant Concentration for penta-
chlorophenol.
Miscellaneous
Additional data regarding the toxicity of PCP to freshwater organisms
are listed in Table 6. The most significant results are from a number of
studies of 3- to 13-week duration showing that the primary subacute effect
of PCP on fish is a reduction in growth rate. Ten studies with salmonid
fish species showed growth inhibition of 10 to 27 percent at PCP concentra-
tions ranging from 3.2 to 28 ug/1 (Chapman, 1969; Matida, et al. 1970; Webb
and Brett, 1973; and Chapman and Shumway, 1978).
The ten percent growth reduction observed by Webb and Brett (1973) for
sockeye salmon occurred at a concentration (3.2 ug/1) which was 6 percent of
the 96-hour LC5Q (58 ug/1) for the test fish. Using the 6 percent factor
with the lowest 96-Hour LC5Q for freshwater fish species (coho salmon, 34
ug/1) would predict reduced growth at a PCP concentration of 2.0 ug/1-
Additional studies indicate that PCP is very toxic to saltwater inver-
tebrate species, particularly to molluscs (Table 6). No larvae of the
Eastern oyster survived a 14-day exposure to 100 ug/1 (Davis and Hidu,
1969). Laboratory tests that assess the impact of toxicants that alter the
structure of settling benthic communities support the conclusion reached
from acute tests, namely, that molluscs are highly sensitive to PCP (Table
6). As little as 7 ug/1 significantly decreased the number of molluscs that
developed from larvae in unfiltered saltwater during a 9-week exposure. A
PCP concentration of 76 ug/1 significantly reduced the total number of ben-
thic macrofauna (Tagatz, et al. 1977).
B-8
-------
Summary
Pentachlorophenol (PCP) is reported to be acutely toxic to freshwater
organisms at concentrations ranging from 34 to 2,000 yg/1. Fish species ap-
pear to be more sensitive to PCP than invertebrate species and salmonid fish
species more sensitive than non-salmonid fish species. However, the
invertebrate data base consists of tests with only two species of clado-
cerans, so the fish-invertebrate comparison is tenuous. Interspecific com-
parisons are further complicated by the apparent effect of pH on PCP tox-
icity. Data from two 24-hour acute studies strongly suggest that PCP is
considerably more toxic at acidic pH values than at alkaline pH values.
Chronic toxicity studies with Daphnia magna, the fathead minnow, and
the saltwater sheepshead minnow indicated that chronic toxicity does not oc-
cur below about 15-40 percent of the 96-hour IC™ concentrations. How-
ever, several growth studies with salmonid fish species demonstrated that
PCP inhibited growth at concentrations between 3.2 and 28 ug/1, concentra-
tions as little as 6 percent of the 96-hour LC5Q.
The toxicity of PCP to freshwater aouatic plants has been studied very
little; the only studies available report chlorosis in algae and in duckweed
at PCP concentrations of 7.5 and 800 pg/1, respectively. Pentachlorophenol
is rapidly absorbed by fishes, but bioconcentration is relatively low
because PCP is rapidly conjugated and excreted.
The toxicity of PCP may be due in part to one or more of the possible
contaminants reported to occur in some batches of PCP, especially in older,
technical grade PCP. Most common among these contaminants are lower chlo-
rinated phenols (which are less toxic) and higher chlorinated condensation
products including dioxins, diphenyl ethers, and dibenzofurans (which may be
more toxic). However, their concentrations in PCP, although variable, are
usually extremely low.
-------
The lowest concentrations of PCP reported to cause adverse effects in
aquatic organisms are 3.2, 7.4, and 9.2 ug/1 which inhibited growth in
salmon and trout and 7.5 ug/1 which produced total chlorosis in algae. The
lowest reported acute toxicity value is 34 ug/1 for coho salmon, and the
lowest reported chronic value is 57 ug/1 for the fathead minnow.
Saltwater fish and invertebrate species have similar sensitivities to
PCP. The range of EC5Q and LC5Q values is from 40 ug/1 for Eastern
oyster embryos to 5,600 ug/1 for juvenile pink shrimp. The range for fish
species is from 38 ug/1 for the pinfish to 442 ug/1 for juvenile sheeps-
head minnows. In general, however, molTuscan species appear to be the most
sensitive of those species tested. An early life stage test with PCP and
the sheepshead minnow resulted in mortality at 88 ug/1, but no effects on
growth or fecundity at concentrations as high as 195 ug/1. Ninety-six-hour
EC,-0 values for three saltwater algal species indicate that PCP may be
more toxic to some plants then to molluscs. The bioconcentration factor for
a polychaete worm was 3,830. Most factors for two mollusc and one fish
species were within the range of 13 to 390.
Only a few additional data for both freshwater and saltwater organisms
are needed to provide the minimum data base requirements specified in the
Guidelines for developing criteria. However, because PCP is very toxic, and
effects commonly occur over a relatively wide range of concentrations, these
few tests need to be conducted.
CRITERIA
The available data for pentachlorophenol indicate that acute and
chronic toxicity to freshwater aquatic life occur at concentrations as low
as 55 and 3.2 ug/l> respectively, and would occur at lower concentrations
among species that are more sensitive than those tested.
B-10
-------
The available data for . pentachlorophenol indicate that acute and
chronic toxicity to saltwater aquatic life occur at concentrations as low as
53 and 34 ug/l» respectively, and would occur at lower concentrations among
species that are more sensitive than those tested.
B-ll
-------
Table I. Acute values for pentachIorophenoI
DO
I
Species
Method*
LC50/EC50
(UQ/I)
Species Mean
Acute Value
(jig/I) Reference
FRESHWATER SPECIES
Cladoceran,
Daphnla magna
Cladoceran,
Daphnla magna
Cladoceran,
Daphnla magna
C 1 adoceran ,
Daphnla magna
Cladoceran,
Daphnla magna
Cladoceran,
Daphnla magna
Cladoceran,
Daphnla magna
Cladoceran,
Daphnla magna
Cladoceran,
Daphnla pulex
Cladoceran,
Daphnla pulex
Coho salmon,
Oncorhynchus klsutch
Coho sa Imon,
Oncorhynchus klsutch
Sockeye salmon,
Oncorhynchus nerka
Sockeye salmon,
s,
s,
s.
s.
s.
s.
s.
s.
s,
s.
s,
s,
s,
s,
u
u
u
u
u
u
u
M
u
u
u
u
u
u
680
260
240
400
400
790
800
600
2,000
2,000
89
34
120
46
U.S. EPA, 1978
Canton
Canton
Canton
Canton
Canton
Canton
475 Adema,
- Canton
2,000 Canton
Davis &
55 Davis &
Davis &
Davis &
& Adema
& Adema
& Adema
& Adema
& Adema
& Adema
1978
i Adema
& Adema
Hoos,
Hoos,
Hoos,
Hoos,
, 1978
, 1978
, 1978
, 1978
, 1978
, 1978
, 1978
, 1978
1975
1975
1975
1975
Oncorhynchus nerka
-------
Table 1. (Continued)
W
I
M
U>
Species
Sockeye salmon,
Oncorhynchus nerka
Chinook salmon,
Oncorhynchus tshawytscha
Rainbow trout,
Salmo galrdnerl
Rainbow trout,
Sal mo gairdnerl
Rainbow trout,
Salmo galrdnerl
Rainbow trout,
Salmo gairdnerl
Rainbow trout,
Salmo gairdnerl
Rainbow trout,
Salmo gairdnerl
Rainbow trout,
Sal mo galrdnerl
Rainbow trout,
Sal mo galrdnerl
Brook trout,
Salvellnus fontinalIs
Goldfish,
Carasslus auratus
Goldfish,
Carasslus auratus
Goldfish,
Carassius auratus
Method*
FT, U
FT, U
S. U
S, U
S, U
S. U
S, U
S, U
S, U
S. U
FT, M
FT, M
FT, M
FT, M
LC50/EC50
(yg/i)
58
72
75
92
85
89
46
92
44
69
128
210
220
230
Species Mean
Acute Value
(liq/l)
68
72
71
128
Reference
Webb 4 Brett, 1973
Iwama & Greer, 1979
Bent ley, et al. 1975
Bent ley, et al. 1975
Davis & Hoos, 1975
Davis 4 Hoos, 1975
Davis 4 Hoos, 1975
Davis 4 Hoos, 1975
Davis 4 Hoos, 1975
Davis 4 Hoos, 1975
Cardwell, et al. 1976
Adelman 4 Smith, 1976
Adelman 4 Smith, 1976
Adelman 4 Smith, 1976
-------
Table 1. (Continued)
Species
Goldfish,
Carasslus auratus
Goldfish,
Carasslus auratus
Goldfish,
Carasslus auratus
Goldfish,
Carassius auratus
Goldfish,
Carasslus auratus
Goldfish,
Carasslus auratus
Goldfish,
Carasslus auratus
Goldfish,
Carasslus auratus
Goldfish,
Carasslus auratus
Goldfish,
Carasslus auratus
Goldfish,
Carasslus auratus
Goldfish,
Carasslus auratus
Goldfish,
Carasslus auratus
Fathead minnow,
Plmephales promelas
Method*
FT,
FT,
FT,
FT,
FT,
FT,
FT,
FT,
FT,
FT,
FT,
FT,
FT,
FT,
M
M
M
M
M
M
M
M
M
M
M
M
M
M
LC50/EC50
tua/D
210
170
170
220
230
240
240
200
190
290
300
200
250
200
Species Mean
Acute Value
(ug/l) Reference
- Adelman &
Adelman &
Adelman &
Adelman &
- Adelman &
Adelman &
Adelman &
Adelman &
Adelman &
Adelman &
Adelman A
Adelman &
220 Adelman &
Adelman &
-------
Table 1. (Continued)
W
I
I—'
ui
Species
^
Fathead minnow.
PImephales promelas
Fathead minnow,
PImephales promelas
Fathead minnow.
PImephales promelas
Fathead minnow,
PImephales promelas
Fathead minnow,
PImephales promelas
Fathead minnow.
PImephales promelas
Fathead minnow,
PImephales promelas
Fathead minnow,
PImephales promelas
Fathead minnow,
PImephales promelas
Fathead minnow.
PImephales promelas
Fathead minnow.
PImephales promelas
Fathead minnow.
PImephales promelas
Fathead minnow.
PImephales promelas
Fathead minnow,
Method*
FT, M
FT, M
FT, M
FT, M
FT, M
FT, M
FT, M
FT, M
FT, M
FT, M
FT, M
FT, M
FT, M
FT, M
LC50/EC50
(U9/D
180
220
180
190
210
220
160
190
190
240
200
200
190
270
Species Mean
Acute Value
(ug/l) Reference
Adelman 4 Smith, 1976
Adelman 4 Smith, 1976
Adelman 4 Smith, 1976
Adelman 4 Smith, 1976
Adelman 4 Smith, 1976
Adelman 4 Smith, 1976
Adelman 4 Smith, 1976
Adelman 4 Smith, 1976
Adelman 4 Smith, 1976
Adelman 4 Smith, 1976
Adelman 4 Smith, 1976
Adelman 4 Smith, 1976
Adelman 4 Smith, 1976
Adelman 4 Smith, 1976
PImephales promelas
-------
Table 1. (Continued)
03
I
Species
Fathead minnow,
Plmephaies promelas
Fathead minnow,
Pimephales promelas
Fathead minnow.
Pimephales promelas
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimephales promelas
Fathead minnow.
Pimephales promelas
Guppy,
Poecllla retlculata
Blueglll,
Lepomls macrochlrus
Blueglll,
Lepomls macrochlrus
B 1 ueg ill.
Lepomis macrochlrus
B 1 ueg i 1 1 ,
Lepomis macrochirus
Polychaete worm (adult).
Neanthes arenaceodentata
Eastern oyster (adult).
Crassostrea vlrgtnlca
Method*
FT, M
FT, M
S, U
FT, M
FT, M
FT, M
FT, M
S, U
S, U
R, M
R, M
S, U
FT, M
Species Mean
LC50/EC50 Acute Value
(pq/l) (ug/l)
230
263
600
221
194
314 212
217 217
60
77
260
305 138
SALTWATER SPECIES
435 435
77
Reference
Adelman & Smith, 1976
Cardwel 1, et al. 1976
Mattson, et al. 1976
Hoi combe, et al.
Manuscript
Rueslnk & Smith, 1975
Rueslnk 4 Smith, 1975
Anderson i Weber,
1975
Bent ley, et al. 1975
Bent ley, et al. 1975
Pruitt, et al. 1977
Prultt, et al. 1977
U.S. EPA, 1980
Schimmel, et al. 1978
-------
Table 1. (Continued)
I
I—'
~J
Species Method*
Eastern oyster, S, U
Crassostrea vlrglnlca
Grass shrimp (larva), S, U
Palaemonetes pugio
Grass shrimp (Intermolt), R, U
Palaemonetes pug to
Grass shrimp R, U
(early premolt),
Palaemonetes pugio
Grass shrimp R, U
( late premolt),
Palaemonetes pugio
Pink shrimp (juvenile), S, U
Penaeus duorarum
Sheepshead minnow FT, M
( juveni le),
Cyprinodon varlegatus
Sheepshead minnow S, U
(1-day fry),
Cyprinodon varlegatus
Sheepshead minnow S, U
(2-wk fry),
Cyprinodon varlegatus
Sheepshead minnow S, U
(4-wk fry),
Cyprinodon varlegatus
Sheepshead minnow S, U
(6-wk fry),
Cyprinodon varlegatus
Species Mean
LC50/EC50 Acute Value
Cug/0 (ug/D
40 77
649
2,632
2,743
436 1,200
5,600 5,600
442
329
392
240
223 442
Reference
Borthwlck & Schimmel,
1978
Borthwick & Schimmel,
1978
Conklln 4 Rao, I978a
Conklln & Rao, 1978a
Conk 1 in & Rao, 1978a
Bent ley, et al. 1975
Parrish, et al. 1978
Borthwick & Schimmel,
1978
Borthwick & Schimmel,
1978
Borthwick & Schimmel,
1978
Borthwick & Schimmel,
1978
Plnflsh (prolarvae),
Lagodon rhomboldes
S, U
38
Borthwick i Schimmel,
1978
-------
Table 1. (Continued)
Species Mean
LC50/EC50 Acute Value
Species Method* (yg/1) (ug/l) Reference
Pinflsh (juvenile), FT, M 53 53 Schliwnel, et al. 1978
Lagodon rhomboldes
Striped mullet (juvenile), FT, M 112 112 Schiimiel, et al. 1978
Mug 11 cephalus
* S = static, FT = flow-through, R = renewal, U = unmeasured, M = measured
00
I
M
oo
-------
Table 2. Chronic values for pentachlorophenol
Species Test*
Limits Chronic Value
(M9/D (ug/»
Cladoceran, LC
Daphnla magna
Fathead minnow, ELS
Pimephales promelas
FRESHWATER SPECIES
180-320 240
45-73 57
Reference
Adema, 1978
Ho I combe, et al,
Manuscript
DO
I
H-
VD
Sheepshead minnow, LC
Cyprlnodon varlegatus
SALTWATER SPECIES
47-88 64
Parrlsh, et al. 1978
* ELS = early life stage; LC = life cycle or partial life cycle
Acute-Chronic Ratios
SpecIes
Cfadoceran,
Daphnla roagna
Fathead minnow,
Pimephales promelas
Sheepshead minnow,
Cyprlnodon varlegatus
Acute
Value
(M.q/D
600
221
442
Chronic
Value
(MQ/D
240
57
64
Ratio
2.5
3.9
6.9
-------
Table 3* Species Mean acute values and acute-chronic ratios for pentachlorophenol
Cd
i
Rank*
Species
Species Mean Species Mean
Acute Value Acute-Chronic
Ratio
U
10
9
8
7
6
5
4
3
2
1
FRESHWATER SPECIES
Cladooeran,
Daphnla put ex
Cladoceran,
Daphnla roagna
Goldfish,
Carasslus auratus
Guppy,
Poecllla retlculata
Fathead minnow,
Plmephales promelas
Blueglll,
Lepomls macrochirus
Brook trout,
Salvellnus fontinalis
Chinook salmon,
Oncorhynchus tshawytscha
Rainbow trout.
Sal mo gairdneri
Sockeye salmon,
Oncorhynchus nerka
Coho salmon,
Oncorhynchus klsutch
SALTWATER SPECIES
2,000
475 2.5
220
217
212 3.9
136
128
72
71
68
55
Pink shrimp,
Penaeus duorarum
5,600
-------
Table 3. (Continued)
W
I
Rank*
6
5
4
3
2
1
Species
Grass shrimp,
Palaemonetes pucjio
Sheepshead minnow,
Cyprinodon varlegatus
Polychaete worm,
Neanthes arenaceodentata
Striped mul let,
Mug i i cepha I us
Eastern oyster,
Crassostrea virgin ica
Pinfish,
Laqodon rhomboldes
Species Mean
Acute Value
1,200
442
435
112
77
53
Species Mean
Acute-Chronic
Ratio
6.9
* Ranked from least sensitive to most sensitive based on species mean
acute value.
-------
Table 4. Plant values for pentochlorophenol
CO
I
M
NJ
Species
Result
Effect
Reference
Alga,
Chi ore) la pyrenoldosa
Duckweed,
Lemna minor
Alga,
Skeletonema costatum
Alga,
Skeletonema costatum
Alga,
Skeletonema costatum
Alga,
Thalassiosira pseudonana
Alga,
Thalassiosira pseudonana
Alga,
Thalassiosira pseudonana
Alga,
Dunaliella tertiolecta
Alga,
FRESHWATER SPECIES
Chlorosis, 7.5
72-hr EC 100
Chlorosis, 800
48 -hr EC 50
SALTWATER SPECIES
Ce 1 1 numbers 20
96- hr EC50
Cel 1 numbers 17
96-hr EC50
Cell numbers 18
96- hr EC50
Cell numbers 205
96- hr EC50
Cell numbers 189
96- hr EC50
Cell numbers 179
96- hr EC50
Cell numbers 206
96-hr EC50
Cell numbers 170
Huang & G loyna,
1968
Blackman, et al
1955
U.S. EPA, 1980
U.S. EPA, 1980
U.S. EPA, 1980
U.S. EPA, 1980
U.S. EPA, 1980
U.S. EPA, 1980
U.S. EPA, 1980
U.S. EPA, 1980
Dunaliella ter t i o 1 ecta
96- hr EC50
-------
Table 5. Residues for pentachlorophenol
B 1 oconcentrat 1 on
Cd
I
1
to
OJ
Species
Goldfish,
Carasslus auratus
Bluegill,
Lepomis macrochlrus
Polychaete worm.
Lanlce conchllega
Blue mussel.
Mytl lus edul Is
Blue mussel ,
Mytl lus edul Is
B 1 ue mus se 1 ,
Mytilus edul Is
Blue mussel,
Mytl lus edul Is
Eastern oyster (adult).
Crassostrea vlrginlca
Eastern oyster (adult).
Crassostrea vlrginlca
Sheepshead minnow
(juveni le).
Cyprlnodon varlegatus
Sheepshead minnow
(adult).
Cyprlnodon varlegatus
Tissue Factor
FRESHWATER
Whole body 1
Edible portion
SALTWATER
Whole body 3
Soft parts
Soft parts
Soft parts
Soft parts
Soft parts
Soft parts
Whole body
Whole body
SPECIES
,000
13
SPECIES
,830
390
326
304
324
78
41
34*
13*
Duration
(days)
5
8
8
8
8
(5 C)
B
(10 C)
8
(15 C)
28
steady- state
in 4
28
steady-state
In 4
28
151
Reference
Kobayashl & Akitake,
1975
Prultt, et al.
Ernst, 1979
Ernst, 1979
Ernst, 1979
Ernst, 1979
Ernst, 1979
Schimmel, et al
Schitnmel, et al
Parrlsh, et al.
Parrish, et al.
1977
. 1978
. 1978
1978
1978
Average of all concentrations
-------
Table 6. Other data for pentachlorophenoI
Result
(ug/l) Reference
to
I
N)
FRESHWATER SPECIES
Tublf Icld worm,
Tublfex tublfex
Tublf Icld worm,
Tublfex tub! f ex
Tub! field worm,
Tublfex tub I fax
Cladoceran,
Daphnla magna
Cladoceran,
Oaphnla magna
Cladoceran,
Oaphnla magna
Cladoceran,
Daphnla magna
Cladoceran,
Daphnla magna
Cladoceran,
Daphnla magna
Cladoceran,
Daphnla magna
Cladoceran,
Daphnla magna
Cladoceran,
Daphnla magna
Cladoceran,
Daphnla magna
Sea larnorev.
24 hrs
24 hrs
24 hrs
21 days
21 days
21 days
21 days
21 days
21 days
21 days
21 days
14 days
14 days
4 hrs
LC50, pH = 7.5
LC50, pH = 8.5
LC50, pH = 9.5
LC50
LC50
LC50
LC50
LC50
LC50
l£50
LC50
LC50
LC50
LC100
266
619
1,294
480
510
400
470
430
490
170
190
440
460
924
Whit ley, 1968
Whit ley, 1968
Whltley, 1968
Adema, 1978
Adema, 1978
Adema, 1978
Adema, 1978
Adema, 1978
Adema, 1978
Adema, 1978
Adema, 1978
Adema, 1978
Adema, 1978
App legate, et
Petromyzon mar I mis
1957
-------
Table 6. (Continued)
Species
Duration
Effect
Result
(ug/I) Reference
03
I
to
Sockeye salmon,
Oncorhynchus nerka
Rainbow trout.
Sal no gairdneri
Rainbow trout,
Sal mo gairdneri
Rainbow trout,
Sal mo gairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gairdner i
Rainbow trout,
Salmo gairdneri
Brown trout,
Salmo trutta
6 wks
48 hrs
4 hrs
5 days
20 days
20 days
21 days
28 days
38 days
41 days
41 days
92 days
28 days
48 hrs
10? growth
inhibition
LC50
LCI 00
LC25
11? growth
inhibition
18? growth
inhibition
19? growth
inhibition
12? growth
inhibition
18? growth
Inhibition
LCI 00
13? growth
inhibition
9? growth
inhibition
27? growth
Inn ibit ion
LC50
3.2
157
924
92
28
28
28
28
28
46
9.2
18
7.4
157
Webb 4 Brett, 1973
Alabaster, 1957
App legate, et al.
1957
Chapman, 1969
Chapman, 1969
Chapman, 1969
Chapman, 1969
Chapman, 1969
Chapman, 1969
Chapman, 1969
Chapman, 1969
Chapman & Shumway,
1978
Matida, et al. 197
Alabaster, 1957
-------
Table 6. (Continued)
03
I
to
Species
Atlantic salmon.
Sal mo salar
Brook trout,
Salvelinus fontlnalls
Goldfish,
Carassius auratus
Fathead minnow,
Plmephales promelas
Guppy,
Poecilia reticulata
Guppy,
Poecilia reticulata
Guppy,
Poecl 1 la reticulata
Guppy,
Poecl 1 la reticulata
Guppy,
Poecl 1 la reticulata
B 1 ueg III,
Lepomis macrochlrus
Alga,
Monochrysis lutheri
Pacific oyster (embryo),
Crassostrea gigas
Eastern oyster (embryo),
Crassostrea v i rg 1 n 1 ca
Duration
24 hrs
336 hrs
336 hrs
336 hrs
24 hrs
21-38 mins
72-93 mins
24 hrs
90 days
336 hrs
12 days
48 hrs
48 hrs
Effect
Altered temper-
ature preference
LC50
LC50
LC50
LC40
LC50, pH = 5.9-6.0
LC50, pH = 7.5-7.6
LC50, pH = 8.9-9.0
LC45
LC50
SALTWATER SPECIES
58% decrease
cell numbers
f>\.6% embryos
abnormal
No embryos
developed
Result
(yg/i)
46
109
175
141
333
924
924
924
462
174
293
55
250
Reference
Peterson
Cardwel 1
Cardwel 1
Cardwel 1
Crandal 1
1959
Crandal 1
1959
Crandal 1
1959
Crandal 1
1959
Crandal 1
1962
Cardwel 1
Woe Ike,
Woe Ike,
Davis &
, 1976
, et al. 1976
, et al. 1976
, et al. 1976
& Goodnight,
& Goodnight,
& Goodnight,
& Goodnight,
& Goodnight,
, et al. 1976
1965
1972
Hidu, 1969
-------
Table 6. (Continued)
CO
I
K)
Eastern oyster (larva),
Crassostrea vlrglnica
Eastern oyster (adult),
Crassostrea vlrglnica
Bay mussel (larva),
Myt)Ius edulIs
Bay mussel (larva),
Mytllus edults
Carpet she I I
Tapes (= Venerupls)
Duration Effect
14 days No larvae survived
192 hrs Reduced she 11
deposition EC50
48 hrs 22.1? abnormal
larvae sal inlty
28 g/kg
48 hrs 69.)? abnormal
larvae sal Inlty
24 g/kg
120 hrs Lethal
Result
(ya/l) Reference
phi 1 ipplnarum
Carpet shel 1
Tapes phi 1 Ipplnarum
Grass shrimp (juvenile),
Palaemonetes pugjo
Grass shrimp (juvenile),
Palaemonetes puglo
Grass shrimp (adult),
Palaemonetes puglo
Grass shrimp (adult),
Palaemonetes pugio
Brown shrimp (juvenile),
Penaeus aztecus
Brown shrimp (juvenile),
Penaeus aztecus
Meiobenthlc
nematodes
24 hrs
96 hrs
96 hrs
9 days
1 hr
96 hrs
96 hrs
9 wks
Bioconcentratlon
factor about 20
No significant
mortal Ity
Bioconcentratlon
factor =1.7
50$ reduction in
lint regeneration
Bioconcentrat Ion
factor = 6.5
No significant
mortality
Bioconcentratlon
factor = 0.26
Decrease In bloma:
and density
too
Davis & Hidu, 1969
34 Schlmmel, et al. 1978
400 Dimlck & Breese, 1965
400 Dimlck & Breese, 1965
100 Tomiyama, et al. 1962
Kobayashl, et al.
1969
515 Schlmmel, et al. 1978
Schlmmel, et al. 1978
473 Rao, et al. 1978
Conk I In & Rao, 19785
195 Schlmmel, et al. 1978
Schlmmel, et al. 1978
622 Cantelmo & Rao, 1978
-------
Table 6. (Continued)
do
i
to
oo
Sp«<- i«s Duration
Benthlc macrofauna 9 wks
Benthlc macrofauna 9 wks
Longnose kllllflsh 96 hrs
(Juvenl le),
Fundulus slml 1 is
Longnose kill I fish 96 hrs
(Juvenl le),
Fundulus slml 1 Is
Striped mullet (juvenile), 96 hrs
Mug! 1 cephalus
Result
Effect (ug/l)
Significantly 76
reduced number
of Individuals
Significantly 7
reduced mol luscs
No significant 306
mortal Ity
Bloconcentratlon
factor = 30
Bloconcentration
factor = 38
Reference
Tagatz, et
Tagatz, et
Schlmmel,
Schlmmel ,
Schimmel ,
al. 1977
al. 1977
et al. 1978
et al. 1978
et al. 1978
-------
REFERENCES
Adelman, I.R. and L.L. Smith, Jr. 1976. Standard test fish development.
Part I. Fathead minnows (Pimephales promelas) and goldfish (Carassius
auratus) as standard fish in bioassays and their reaction to potential ref-
erence toxicants. Ecol. Res. Ser. EPA 600/3-76-061a. U.S. Environ. Prot.
Agency, Duluth, Minn.
Adema, D.M.M. 1978. Daphnia magna as a test animal in acute and chronic
toxicity tests. Hydrobiologia 59: 125.
Akitake, H. and K. Kobayashi. 1975. Studies on the metabolism of chloro-
phenols in fish - III. Isolation and identification of a conjugated PCP ex-
creted by goldfish. Bull. Jap. Soc. Sci. Fish. 41: 322.
Alabaster, J.S. 1957. Toxicity of weedkilling, algicides and fungicides to
trout. Jn_: Proc. 4th Brit. Weed Cont. Conf., Brighton, p. 84.
Anderson, P.O. and L.J. Weber. 1975. Toxic resoonse as a Quantitative
function of body size. Toxicol. Appl. Pharmacol. 33: 471.
Applegate, V.C., et al. 1957. Toxicity of 4,346 chemicals to larval lam-
preys and fishes. U.S. Fish Wild!. Ser. Spec. Sci. Rep. Fish. No. 207.
B-29
-------
Bentley, R.E., et al. 1975. Acute toxicity of pentachlorophenol to blue-
gill (Lepomis macrochirus). rainbow trout (Salmo gairdneri), and pink shrimp
(Penaeus duorarum). Order No. WA-6-99-1414-B. Criteria Branch, U.S.
Environ. Prot. Agency.
Bevenue, A. and H. Beckman. 1967. Pentachlorophenol: A discussion of its
properties and its occurrence as a residue in human and animal tissues.
Res. Rev. 19: 83.
Blackman, G.E., et al. 1955. The physiological activity of substitute
phenols. I. Relationships between chemical structure and physiological
activity. Arch. Biochem. Biophys. 54: 45.
Borthwick, P.M. and S.C. Schimmel. 1978. Toxicity of pentachlorophenol and
related compounds to early life stages of selected estuarine animals. In.:
K.R. Rao, (ed.), Pentachlorophenol: Chemistry, Pharmacology and Environ-
mental Toxicology. Plenum Press, N.Y. p. 141.
Buser, H.R. and H.P. Bosshardt. 1976. Determination of polychlorinated
dibenzo-p-dioxins and dibenzofurans in commercial pentachlorophenols by com-
bined gas chromatography - mass spectrometry. Jour. Assoc. Off. Agri.
Chem. 59: 562.
Cantelmo, F.R. and K.R. Rao. 1978. Effects of pentachlorophenol on the
meiobenthic nematodes in an experimental system. Jji: K.R. Rao, (ed.), Pen-
tachlorophenol: Chemistry, Pharmacology and Environmental Toxicology.
Plenum Press, N.Y. p. 165.
B-30
-------
Canton, J.H. and D.M.M. Adema. 1978. Reproducibility of short-term and re-
production toxicity experiments with Daphnla magna and comparison of the
sensitivity of Daphnia magna with Daphnia pulex and Daphnia cucullata in
short-term experiments. Hydrobiol. 59: 135.
Cardwell, R.D., et al. 1976. Acute toxicity of selected toxicants to six
species of fish. U.S. Environ. Prot. Agency Ecol. Res. Ser. EPA
600/3-76-008. U.S. Environ. Prot. Agency, Duluth, Minn. 117 pp.
Chapman, G.A. 1969. Toxicity of pentachlorophenol to trout alevins. Ph.D.
dissertation. Oregon State University, Corvallis, Oregon. 87 pp.
Chapman, G.A. and D.L. Shumway. 1978. Effects of sodium pentachlorophenate
on survival and energy metabolism of embryonic and larval steelhead trout.
In: K. R. Rao (ed.), Pentachlorophenol: Chemistry, Pharmacology and
Environmental Toxicology. Plenum press, New York. p. 285.
Conklin, P.J. and K.R. Rao. 1978a. Toxicity of sodium pentachlorophenate
(Na-PCP) to the grass shrimp, Palaemonetes pugio, at different stages of the
molt cycle. Bull. Environ. Contam. Toxicol. 20: 275.
Conklin, P.J. and K.R. Rao. 1978b. Toxicity of sodium pentachlorophenate
to the grass shrimp, Palaemonetes pugio, in relation to the molt cycle.
In: K.R. Rao (ed.), Pentachlorophenol: Chemistry, Pharmacology and Envi-
ronmental Toxicology. Plenum Press, N.Y. p. 181.
B-31
-------
Crandall, C.A. and C.J. Goodnight. 1959. The effect of various factors on
the toxicity of sodium pentachlorophenate to fish. Limnol. Oceanog. 4: 53.
Crandall, C.A. and C.J. Goodnight. 1962. Effects of sublethal concentra-
tions of several toxicants on growth of the common guppy, Lebistes
reticulatus. Limnol. Oceanog. 7: 233.
Davis, H.C. and H. Hidu. 1969. Effects of pesticides on embryonic develop-
ment of clams and oysters and on survival and growth of the larvae. U.S.
Fish Wild. Ser. Fish. Bull. 67: 393.
Davis, J.C. and R.A. Hoos. 1975. Use of sodium pentachlorophenate and de-
hydroabietic acid as reference toxicants for salmonid bioassays. Jour.
Fish. Res. Board Can. 32: 411.
Dimick, R.E. and W.P. Breese. 1965. Bay mussel embryo bioassay. In:
Proc. 12th Pacific Northwest Industrial Waste Conf., Univ. Wash., Seattle.
p. 165.
Ernst, W. 1979. Factors affecting the evaluation of chemicals in labora-
tory experiments using marine organisms. Ecotoxicol. Environ. Safety.
3: 90.
Firestone, D., et al. 1972. Determination of polychlorodibenzo-p-dioxins
and related compounds in commercial chlorophenols. Jour. Assoc. Off. Agri.
Chem. 59: 85.
B-32
-------
Holcombe, G.W., et al. (manuscript) Effects of phenol, 2,4-dimethylphenol,
2,4-dichlorophenol and pentachlorophenol on embryo, larval, and early juve-
nile fathead minnows (Pimephales promelas). U.S. Environ. Prot. Agency,
Duluth, Minn.
Huang, J. and E.F. Gloyna. 1968. Effect of organic compounds on phytosyn-
thetic oxygenation. I. Chlorophyll destruction and suppression of photo-
synthetic oxygen production. Water Res. 2: 347.
Iwama, G.K. and G.L. Greer. 1979. Toxicity of sodium pentachlorophenate to
juvenile Chinook salmon under conditions of high loading density and con-
tinuous-flow exposure. Bull. Environ. Contam. Toxicol. 23: 711.
Jensen, S. and L. Renberg. 1972. Contaminants in pentachlorophenol:
chlorinated dioxins and predioxins (chlorinated hydroxy-diphenylethers).
Ambio 1: 62.
Kobayashi, K. and H. Akitake. 1975. Studies on the metabolism of chloro-
phenols in fish. I. Absorption and excretion of PCP by goldfish. Bull.
Jap. Soc. Sci. Fish. 41: 87.
Kobayashi, K., et al. 1969. Studies on the metabolism of pentachloro-
phenate, a herbicide, in aquatic organisms. I. Turnover of absorbed PCP in
Tapes philippinarum. Bull. Jap. Soc. Sci. Fish. 35: 1179.
B-33
-------
Lech, J.J., et al. 1978. Studies on the uptake, disposition and metabolism
of pentachlorophenol and pentachloroanisole in rainbow trout (Salmo
gairdneri). Jin: K. R. Rao (ed.), Pentachlorophenol: Chemistry, Pharma-
cology and Environmental Toxicology. Plenum Press, New York. p. 107.
Matida, Y., et al. 1970. Study on the toxicity of agricultural control
chemicals in relation to freshwater fisheries management. No. 5. Some ef-
fects of sodium pentachlorophenate to freshwater fishes. Bull. Freshwater
Fish. Res. Lab. 20: 127.
Mattson, V.R., et al. 1976. Acute toxicity of selected organic compounds
to fathead minnows. Ecol. Res. Ser. EPA 600/3-76-097. U.S. Environ. Prot.
Agency, Duluth, Minn. 13 pp.
Parrish, P.R., et al. 1978. Chronic toxicity of chlordane, trifluralin,
and pentachlorophenol to sheepshead minnows (Cyprinodon variegatus). Report
No. EPA 600/3-78-010: 1.
Peterson, R.H. 1976. Temperature selection of juvenile Atlantic salmon
(Salmo salar) as influenced by various toxic substances. Jour. Fish. Tes.
Board Can. 33: 1722.
Plimmer, J.R., et al. 1973. Mass spectrometric identification of the
hepta- and octa- chlorinated dibenzo-p-dioxins and dibenzofurans in tech-
nical pentachlorophenol. Jour. Agri. Food Chem. 21: 90.
B-34
-------
Pruitt, 6.W., et al. 1977. Accumulation and elimination of pentachloro-
phenol by the bluegill, Lepomis macrochirus. Trans. Am. Fish. Soc.
106: 462.
Rao, K.R., et al. 1978. Inhibition of limb regeneration in the grass
shrimp, Palaemonetes pugio, by sodium pentachlorophenate. _In: K.R. Rao
(ed.), Pentachlorophenol: Chemistry, Pharmacology and Environmental Toxi-
cology. Plenum Press, N.Y. p. 193.
Ruesink, R.G. and L.L. Smith, Jr. 1975. The relationship of the 96-hour
LC50 to ttie 1etha1 threshold concentration of hexavalent chromium, phenol,
and sodium pentachlorophenate for fathead minnows (Pimephales promelas
Rafinesque). Trans. Am. Fish. Soc. 104: 567.
Schimmel, S.C., et al. 1978. Effects of sodium pentachlorophenate on
several estuarine animals: Toxicity, uptake, and depuration. l£: K.R. Rao
(ed.), Pentachlorophenol: Chemistry, Pharmacology an Environmental Toxi-
cology. Plenum Press, N.Y. p. 147.
Tagatz, M.E., et al. 1977. Effects of pentachlorophenol on the development
of estuarine communities. Jour. Toxicol. Environ. Health. 3: 501.
Tomiyama, T., et al. 1962. The toxic effect of pentachlorophenate, a her-
bicide, on fishery organisms in coastal waters. IV. The effect on
VenenjPis pnilJPPinarum of PCP which was constantly supplied or absorbed on
estuary mud. Bull. Jap. Soc. Sci. Fish. 28: 422.
8-35
-------
U.S. EPA. 1978. In-depth studies on health and environmental impacts of
selected water pollutants. U.S. Environ. Prot. Agency, Contract No.
68-01-4646.
U.S. EPA. 1980. Unpublished laboratory data. Environmental Research
Laboratory - Gulf Breeze.
Webb, P.W. and J.R. Brett. 1973. Effects of sublethal concentrations of
sodium pentachlorophenate on growth rate, food conversion efficiency, and
swimming performance in underyearling sockeye salmon (Oncorhynchus nerka).
Jour. Fish. Res. Board Can. 30: 499.
Whitley, L.S. 1968. The resistance of tubificid worms to three common pol-
lutants. Acta Hydrobiol. 32: 193.
Woelke, C.E. 1965. Development of a bioassay method using the marine
algae, Monochrysis lutheri. Wash. Dep. Fish. Shellfish Progress Rep. 9 p.
Woelke, C.E. 1972. Development of a receiving water duality bioassay cri-
terion based on the 48-hour Pacific oyster (Crassostrea gigas) embryo.
Wash. Dep. Fish. Tech. Rep. No. 9: 1.
B-36
-------
Mammalian Toxicology and Human Health Effects
INTRODUCTION
Residues of pentachlorophenol (PCP) have been found in food,
water, and human tissues (Bevenue and Beckman, 1967; Johnson and
Manske, 1977; Buhler, et al. 1973; Shafik, 1973; Kutz, et al.
1978). it does not follow, however, that in each instance the
total residue results directly from PCP applications. Yang, et al.
(1975) suggested the formation of PCP in the Rhesus monkey follow-
ing administration of hexachlorobenzene (HCB). Hexachlorobenzene
is a registered pesticide and is used as a fungicide. It is also a
frequent contaminant in commercial PCP and chlorinated solvents.
HCB is the most commonly found chlorinated hydrocarbon in meat
(Conklin and Fox, 1978). Consequently, the degradation of HCB to
PCP may account for part of the PCP residue present in certain com-
modities. Lui and Sweeney (1975) and Mehendale, et al. (1975) re-
ported the isolation of PCP from the urine of rats that had been
dosed with HCB. Microsomal preparations from rat liver were able
to produce one or more chloroohenols, including PCP from HCB
(Mehendale, et al. 1975). KOSS and Koransky (1978) administered
labeled HCB to rats and collected urine and feces for four weeks.
HCB was metabolized to PCP, tetrachlorohydroquinone, and pentachlo-
rothiophenol. Twenty-eight percent of the HCB was recovered as PCP
in the urine and 16 oercent was recovered as PCP in the feces.
These results suggest that metabolism of HCB to PCP can be a sig-
nificant consideration. Karapally, et al. (1973) obtained tenta-
tive gas chromatographic identification of PCP in the urine of rab-
bits receiving 14C-labeled lindane (tf-1,2,3,4,5,6-hexachloro-
C-l
-------
cyclohexane). Rats given 8 mg HCB/kg for 19 days had tissue resi-
dues of HCB and metabolites consisting of PCP and small amounts of
2,3,4,6-tetrachlorophenol, 2,3,5,6-tetrachlorophenol, 2,4,6-tri-
chlorophenol, and pentachlorobenzene (Engst, et al. 1976a). PCP,
tetrachlorophenol, and trichlorophenols are also metabolites of
lindane in the rat (Engst, et al. 1976b). Lindane applied to let-
tuce growing outdoors degraded to free trichlorophenol, 2,3,4,6-
tetrachlorophenol, pentachlorophenol, conjugates of the latter two
compounds, and unidentified water-soluble products (Kohli, et al.
1976) .
The results of these studies suggest several possible sources
for the residues of PCP in foods and tissues, in addition to resi-
dues resulting from the direct use of PCP.
EXPOSURE
Ingestion from Water and Food
Buhler, et al. (1973) reported pentachlorophenol levels of
0.06 yg/1 in finished drinking water prepared from raw water con-
taining 0.17 ug/1. The calculated daily dietary exposure is from 1
to 6 yg/person/day (Duggan and Corneliussen, 1972) .
Pentachlorophenol is absorbed from the digestive tract. Pen-
tachlorophenol was detected at levels of 0.01 to 0.04 mg/kg in 13
of 240 food composites collected from August, 1974 to July, 1975
(Johnson and Manske, 1977). The highest residue (0.04 mg/kg) re-
ported was in the food category of sugars and adjuncts.
A bioconcentration factor (BCF) relates the concentration of a
chemical in aquatic animals to the concentration in the water in
which they live. The steady-state BCFs for a lipid-soluble com-
C-2
-------
pound in the tissues of various aquatic animals seem to be propor-
tional to the percent lipid in the tissue. Thus the per capita
ingestion of a lipid-soluble chemical can be estimated from the per
capita consumption of fish and shellfish, the weighted average per-
cent lipids of consumed fish and shellfish, and a steady-state BCF
for the chemical.
Data from a recent survey on fish and shellfish consumption in
the United States were analyzed by SRI International (U.S. EPA,
1980). These data were used to estimate that the per capita con-
sumption of freshwater and estuarine fish and shellfish in the
United States is 6.5 g/day (Stephan, 1980). In addition, these
data were used with data on the fat content of the edible portion of
the same species to estimate that the weighted average percent lip-
ids for consumed freshwater and estuarine fish and shellfish is 3.0
percent.
A measured steady-state bioconcentration factor of 13 was
obtained for pentachlorophenol using sheepshead minnows (Parrish,
et al. 1978). Similar sheepshead minnows contained an average of
about 3.6 percent lipids (Hansen, 1980). An adjustment factor of
3.0/3.6 = 0.83 can be used to adjust the measured BCF from the 3.6
percent lipids of the fathead minnow to the 3.0 percent lipids that
is the weighted average for consumed fish and shellfish. Thus, the
weighted average BCF for pentachlorophenol and the edible portion
of all freshwater and estuarine aquatic organisms consumed by Amer-
icans is calculated to be 13 x 0.83 = 11.
C-3
-------
Inhalation
Data concerning exposure of the general public by inhalation
of pentachlorophenol are not available. However, some exposure
data and criteria are available for industrial situations. The
threshold limit value is 0.5 mg/m , and levels greater than 1.0
mg/m cause respiratory irritation in unacclimated persons FAmeri-
can Industrial Hygiene Association (AIHA), 1970]. This value of
0.5 mg/m provides a moderate margin of safety for an 8 hr/day, 5
day/week exposure.
Wyllie, et al. (1975) sampled air five times at 11 sites in a
plant treating 2.5 million board feet of lumber annually. Average
air PCP levels ranged from 0.263 to 1.888 yg/m . ^he highest PCP
level reported was 15 yg/m in an air sample from the pressure
treating room. The air samples were collected for an average of
six hours. Air PCP levels in storage areas ranged from 0.009 to 9.0
ug/m3. Serum PCP levels in six workers averaged 1-2 mg/1. Urine
PCP levels were 0.08 to 0.3 mg/1. The highest serum PCP level found
was 3.9 mg/1. PCP levels in the one control reported were 0.04 to
0.07 mg/1 in serum and 0.002 to 0.004 mg/1 in urine.
The resulting inhalation exposure can be estimated using the
above maximum air level of 15 ug/m as follows. With an average
minute respiratory volume of 26 I/minute, approximately four times
resting volume, a worker would inhale 12 m of air during an 8-hour
work period. This ventilation rate includes hard work periods, as
well as less strenuous activity and rest. Because there is no
reliable information available on the pulmonary deposition of PCP
vapor or particles, the inhalation dose calculations assume 100
C-4
-------
percent deposition and retention. The resulting pentachlorophenol
exposure at an air level of 15 yg/m3 is 0.180 mg/person/day. For a
70 kg individual, the resulting exposure rate is 0.0026 mg/kg/day.
Under steady-state conditions the same amount of chemical will be
excreted as is absorbed per day. Assuming a daily urinary void of
1.4 I/day, the predicted urine level resulting from the air expo-
sure level of 15 yg/m3 would be 0.180 mg/1.4 1 = 0.13 mg/1. The
resulting value of 0.13 mg/1 falls between the observed urine lev-
els of 0.08 to 0.3 mg/1 reported by Wyllie, et al. (1975). Conse-
quently, all of the inhalation exposure can be accounted for by the
PCP levels in the urine. At the same time, since the calculations
maximized inhalation doses and the range of urine values actually
measured exceeded the calculated urine level, it is reasonable to
assume that there was also exposure from oral_or dermal routes.
Measured air and urine PCP levels associated with three types
of wood treating operations in an Oregon wood treating plant are
shown in Table 1 (Arsenault, 1976). The maximum air level of 0.297
mg/m (Table 1) is considerably higher than the 0.015 mg/m3 maximum
level reported by Wyllie, et al. (1975). Rapp (1978), in present-
ing data obtained by industrial hygiene surveys conducted by Dow
Chemical Company scientists at 28 users' sites, reported an unusu-
ally high PCP level of 65 mg/m3.
The above data can be used to estimate inhalation exposure
(Table 2). The assumptions used include: resting minute respira-
tory volume (tidal volume times respiratory rate) =61, moderate
exercise minute respiratory volume = 24 1, heavy exercise minute
respiratory volume = 100 1; pulmonary deposition and retention of
100 percent; 70 kg person; 8-hour exposure.
-------
TABLE 1
Air and Urine PGP Concentration from
Plants and Mill Workers in Oregon*
Air Level - mg/m
Operation Average Maximum
Dip 0.019 0.019
Spray 0.006 0.026
Pressure 0.014 0.297
Urine - mg/1
Average Range
2.83 0.12 - 9.68
0.98 0.09 - 2.58
1.24 1.24 - 5.57
*Source: Arsenault, 1976
C-6
-------
TABLE 2
Estimated Exposures from Reported Air PCP Concentrations
o
i
Minute respira-
tory volume:
m air/8 hr:
Air Levelt
Resting
6 1/min
2.88 m3
Condition
Moderate Exercise
24 1/min
11.52 m3
Estimated Exposure
Heavy Exercise
100 1/min
48 m3
0.006 mg/in /day
0.014
0.015
0.019
0.026
0.297
0.00025 mg/kg/day
0.00058
0.00062
0.00078
0.00107
0.0122
0.001 mg/kg/day
0.0023
0.0025
0.0031
0.0043
0.0489
0.0041 mg/kg/day
0.00958
0.0103
0.0130
0.0178
0.2037
-------
The important variable in this approach to estimating exposure
is the amount of air inhaled, which is directly related to the
amount of muscular work. It is unlikely that a typical worker is
represented by either the resting or heavy exercise breathing rates
for the entire 8-hour work period. Consequently, a reasonable
assumption would be to use the moderate exercise values, which
represent respiratory values equal to four times the resting rates.
The next step is to compare total inhalation exposure with the
amount of PC? found in the urine in the study reported by Arsenault
(1976). For the dip treaters, the average urine PCP concentration
value of 2.83 mg/1 multiplied by the assumed daily urine/volume of
1.4 1 results in an approximate overall exposure of 3.96 mg
PCP/person. This calculation assumes 100 percent excretion in the
urine, which is not the case as pointed out later in this document;
nonetheless, this assumption will suffice for the purpose of making
the following calculations. The corresponding inhalation exposure,
assuming moderate exercise and an average air level of 0.019 mg/m ,
is 0.0031 mg/kg, or 0.217 mg/person. In this instance, inhalation
accounts for 5.5 percent of the dose for workers in a dipping oper-
ation. The pressure treaters had an average urine level of 1.24
mg/1, which results in an estimated total exposure of 1.74 mg/per-
son. The average air level of 0.014 mg/m yields an inhalation
exposure of 0.0023 mg/kg, or 0.16 mg/person. The resulting esti-
mated inhaled dose is 9.2 percent of the calculated total body
dose.
In a simple two-subject inhalation trial, 76-38 percent of a
calculated respired dose was eliminated within seven days. Peak
C-8
-------
urine PCP levels occurred within 48 hours post-exposure (Casarett,
et al. 1969).
Dermal
Pentachlorophenol can be absorbed through the intact skin.
Pentachlorophenol dissolved in oil solvents has an acute dermal
lethal dose of 60 to 200 mg/kg in rabbits (Deichmann, et al. 1942).
Quantitative dermal absorption data for man are not available.
While it is not possible to separate oral, respiratory, and
dermal exposures, except experimentally, it is possible to estab-
lish estimates of total body exposures. Pentachlorophenol is pri-
marily excreted in the urine and has a half-life in man of 1.25
days. Simulated repeated daily ingestion of 0.1 mg PCP/kg indicat-
ed that an uptake-elimination equilibrium is reached after nine
days of exposure (Braun, et al. 1978) . Thenefore, the urine PCP
concentration can be used to estimate total body exposure. The
accuracy of the calculations is limited by the care with which
urine samples are collected. The most useful data would be based
on 24-hour urine collections or on levels reported based on mOsmols
of urine solute. In the absence of these data, the urine levels may
range by a factor of 2 to 3 in either direction, depending on volume
of fluid intake, perspiration, and presence or absence of renal
tubular disease. Even with these restrictions, the calculated
exposures are of value in estimating the probable exposure magni-
tude. The calculated exposures in Table 3 assume a daily urine
volume of 1.4 1 for a 70 kg adult, steady-state conditions, and 90
percent elimination of the dose in urine and 10 percent in feces.
In addition to the studies on occupational exposures cited above,
C-9
-------
TABLE 3
Comparison of PCP Biotransformation in Mammals
O
I
nose & Peak Blood Time To
Species and Reference Route Level Peak Level
Man: Braun, et al. 0.1 mg/kq 0.248 ppm 4 hr
(1977) Oral
Rat: Braun, et al. 10 mq/kq 45 ppm 4-6 hr
(1977) Male (plasma)
Oral
10 mg/kq 45 ppm 4-6 hr
Female (plasma)
Oral
100 mg/kq
Male
Oral
100 mg/kq
1? Amsa 1 o
Plasma Excretion in Urine
Half -Life and Feces
30.2 hr Peak at 42 hr; half-
life for PCP was 33
hr; half-life for
PCP glucuronide was
12.7 hr
80% in urine
19% in feces
78% in urine
19% in feces
13 hr - =40 hr;
females: o< =13 hr, /S =33 hr
Urine: 75% as PCP; 9%
as PCP-qlucuronide; 16%
as TCH*.
Half-lives were 24 hr
for PCP, 25 hr for
PCP-qlucuron ide ,
and 32 hr for TCH.
See 100 mq/kg male data
above. Urine was pooled.
Oral
-------
TABLE 3 (Continued)
O
I
Dose & Peak Blood Time To Plasma
Species and Reference Route Level Peak Level Half-Life
Monkey: Dcaun and
Sauerhoff (1976) 10 mg/kq 10-30 12-24 ht 72 hr
Male ppm
Oral
10 mg/kg 10-30 ppm 12-24 he 84 ht
Female
Excretion in Urine Metabolites Found,
and Feces Comments
Urine half-life In urine as unchanged
41 hr PCPj no metabolites.
Urine half-life 92 hr
360 hr after
single dose: 70% in
urine; 18% in feces;
11% remained in
tissues.
Mouse: Jakobson and
Yllner (1971)
15-37 mg/kq NR
i.P. or s.c.
NR
NR
72-83% excreted in
urine in 4 days;
about half in 24 hr;
5-7% in feces.
About 45% as unchanged
PCP; 14% as PCP conju-
gate; 40% as TCH.
Kat: Ahlborg, et al.
(1974)
25 mg/kq
i.p.
NR
NR
NR
70% in urine in
24 hr
43% as unchanged PCP;
5% as TCH; 38% as TCH
conjugate; 14% as PCP
conjugate.
Mouse: Ahlborg, et al.
(1974) 25 ray/kg
*TCII - Tetrachlorohydroquinone
NR - Not reported
i.p. - Tntraperitoneal
s.o. - Subcutaneous
NR
NR
NR
70% in urine in
24 hr
41% as unchanged PCP;
24% as TCH; 22% as TCH
conjugate; 13% as PCP
conjugate.
-------
Kutz, et al. (1978) found an arithmetic average of 6.3 ug PCP/1 in
354 of 418 urine samples (84.0 percent) analyzed. Cranmer and
Freal (1970) reported urine levels ranging from 2 to 11 yg/1 for
the general population in a small number of samples.
Exposure estimates based on reported urine PGP levels are
given in Table 4. These represent total body exposures from all
sources and routes.
Duggan and Corneliussen (1972), using dietary levels, calcu-
lated daily exposures of 0.001 to 0.006 mg PCP/person/day. Using
the reported urine values and calculated exposures in Table 4, the
exposure appears to be in the range of 0.010 to 0.017 mg/person/day
for the general population and 1.5 to 4.4 mg for occupational set-
tings.
PHARMACOKINETICS
Absorption
The pharmacokinetic characteristics for PCP are summarized in
Table 3.
The half-life for absorption in man following ingestion of a
single dose of 0.1 mg PCP/kg was found to be 1.3 + 0.4 hour, with a
peak plasma concentration of 0.248 mg/1 occurring four hours after
ingestion (Braun, et al. 1978) . Braun, et al. (1978) further re-
ported that a simulation of repeated daily ingestion of 0.1 mg
PCP/kg indicated that pentachlorophenol would reach 99 percent of
steady-state in 8.4 days with a plasma concentration maximum of
0.491 mg/1.
3raun and Sauerhoff (1976) administered single oral doses of
10 mg PCP/kg in corn oil to three male and three female Rhesus mon-
G-12
-------
TABLE 4
Estimated Total Body PCP Exposures for a 70 kg Person Based on
Reported Urine PCP Levels and Assumed Daily Urine Void of
1.4 1 with 90% Urinary Excretion
Urine Level
(mg/1)
0.0063
0.011
2.83
i
£ 0.98
1.24
2.6
1.6
Reference
Kutz, et al. 1978
Cranmer and Freal, 1970
Arsenault, 1976
Arsenault, 1976
Arsenault, 1976
Casarett, et al. 1969
Casarett, et al. 1969
Estimated
mg/person/day
0.0098
0.017
4.40
1.52
1.93
4.04
2.49
Exposure
nig/kg/day
0.00014
0.00024
0.0629
0.0218
0.0276
0.0578
0.0356
-------
keys. The half-lives for absorption were 3.6 hours (males) and 1.8
hours (females) . Monkeys given a single dose of 10 mg PCP/kg at-
tained peak plasma levels of 10 to 30 ppm in 12 to 24 hours. Braun,
et al. (1977) found that rats administered single oral doses of 10
mg PCP/kg had peak plasma concentrations of 45 ppm in 4 to 6 hours.
Distribution
The quantity of PCP in fat has been investigated in many stud-
ies. Larsen, et al. (1975) examined the tissue distribution of PCP
in rats following oral administration, and found low levels in fat
relative to other tissues.
Braun and Sauerhoff (1976) recovered 11.7 and 11.2 percent,
respectively, of the 10 mg/kg dose in the tissues of two female
monkeys 360 hours after administration. The largest amount of the
PCP recovered, 65 to 83 percent, was found in-the liver and small
and large intestines combined (Table 5). All of the other tissues,
including brain, fat, muscle, bone, and remaining soft tissues,
contained only 2 to 3.5 percent of the dose.
In rats, nine days after a single 10 mg/kg dose, 0.44 percent
of the dose remained in the body, with 82 percent of the residue lo-
cated in the liver and kidney (Braun, et al. 1977). In a study in
which rats were necropsied at 4, 24, 48, 72, and 120 hours post-
dosing, the highest levels among ten selected tissues were found in
liver and kidney. The lowest levels were found in brain, spleen,
and fat. Except for liver in female rats, and liver and kidney in
male rats, the plasma PCP levels were higher than organ levels.
A study by Casarett, et al. (1969) of blood and urine PCP con-
centrations of occupationally exposed individuals suggests a ratio
C-14
-------
TABLE 5
14
Tissue Concentrations of C Activity from
14
Two Female Monkeys Administered 10 mg C PCP/kg*
Tissue
Liver
Small Intestine
Large Intestine
Other3
TOTAL
Percentage
Female 1
1.38
7.06
1.28
1.98
11.70
of Dose
^emale 2
0.81
2.94
3.91
3.54
11.20
*Source: Braun and Sauerhoff, 1976
aOther tissues = adrenals, brain, gall bladder, kidney,
lung, ovaries, pancreas, spleen, stomach, urinary
bladder, uterus, vagina, heart, bone, skin, fat,
muscle, meat, carcass.
C-15
-------
of plasma to urine PCP concentrations of 1.5 to 2.5. Wyllie, et al.
(1975) reported that the PCP levels in the urine of six chronically
exposed workers in a small wood treatment plant were much lower
than those in serum. Levels of PCP in the urine averaged 163.8 ppb
for the exposed individuals, while serum PCP levels averaged 1,372
ppb over the same period of time.
Reported cases of acute intoxication frequently present higher
PCP concentrations in the urine than in the plasma. Animal studies
with single doses also show this pattern. Plasma and urine PCP
concentrations were linearly related up to about 1.0 mg/1; above
1.0 mg/1 the plasma levels reached a plateau approaching 10 mg/1
with increasing levels of PCP in the urine.
Data for tissue distribution following uptake of PCP by man is
derived mainly from autopsy results of fatal cases of PCP intoxica-
tion (Mason, et al. 1965; Gordon, 1956; Armstrong, et al. 1969).
Cretney (1976) reported PCP residues from a suicide as: blood, 173
mg/1; urine, 75 mg/1; liver, 225 mg/kg; and kidney, 116 mg/kg.
From available data, levels associated with acute lethal toxicosis
can be estimated. Levels in blood, liver, and kidney are most
meaningful. Levels in urine can be variable, depending on how much
urine was in the bladder at the time of ingestion. Residues asso-
ciated with acute toxicosis and death are: blood, 50 to 176 mg/1;
liver, 62 to 225 mg/kg; and kidney, 28 to 123 mg/kg.
Armstrong, et al. (1969) reported analysis of fat tissue ob-
tained from an infant exposed to a lethal concentration of Na-PCP
in diapers and hospital linen. Residues were: kidney, 2.8 mg/kg;
adrenal, 2.7 mg/kg; heart and blood vessel, 2.1 mg/kg; and fat, 3.4
C-16
-------
mg/kg. Shafik (1973) found an average of 26.3 yg PCP/kg in 18 human
fat samples of unspecified origin.
Metabolism
Braun, et al. (1978) determined the metabolism and pharmaco-
kinetics of PCP in four male volunteers ingesting 0.1 mg PCP/kg.
Approximately 74 percent of the dose was eliminated in the urine as
PCP, and 12 percent was eliminated in urine as PCP-glucuronide.
Additionally, 4 percent of the dose was eliminated in the feces as
PCP and PCP-glucuronide.
PCP in mice is detoxified by conjugation and metabolism
(Jakobsen and Yllner, 1971). Approximately 21 percent of the in-
jected C activity was found to consist of 14C-labeled tetrachlo-
rohydroquinone (TCH), which was possibly conjugated in the urine.
Rats excrete 75 percent of the PCP in the urine as unchanged PCP, 16
percent as TCH, and 9 percent as PCP-glucuronide (Braun, et al.
1977) . in the plasma most of the PCP is unchanged, with a small
amount of PCP-glucuronide present. TCH was not detected in rat
blood plasma.
Ahlborg (1978) found that rats dechlorinate PCP to form TCH
and trichloro-p-hydroquinone, but not tetrachlorophenol or tri-
chlorophenol. Ahlborg found the TCH to be conjugated in the urine,
while Braun, et al. (1977) reported TCH was unconjugated in their
study. The Rhesus monkey was found to eliminate PCP unchanged in
the urine, with no metabolites detected (Braun and Sauerhoff,
1976) .
:-i7
-------
Excretion
In man and experimental animals the primary mode of excretion
for PCP is urinary (Deichmann, et al. 1942; Jakobsen and Yllner,
1971; Larsen, et al. 1975; Braun, et al. 1978).
In man the plasma PCP half-life is 30.2 + 4.0 hours. The
half-lives for elimination of PCP and PCP-glucuronide from urine
are 33.1 + 4.5 hr and 12.7 + 5.4 hr, respectively. The dynamics of
elimination in man are described by a one-compartment, open-system
model with first-order absorption, enterohepatic circulation, and
first-order elimination (Braun, et al. 1978).
Braun and Sauerhoff (1976) found that the monkey eliminated
PCP more slowly than other animals. In two monkeys, 360 hours
after a single oral dose of 10 mg/kg, 70 percent of the dose was
eliminated in the urine, 18 percent in the £eces, and 11 percent
remained in the carcass. Excretion by the kidney was a first-order
process, characterized by half-lives of 40.8 hr (males) and 92.4 hr
(females). Plasma levels decreased by a first order process with
half-lives of 72 hr (males) and 83.5 hr (females).
The pharmacokinetics of PCP in rats given oral doses of 10
mg/kg are summarized in Table 6, taken from Braun, et al. (1977).
The rat eliminates PCP more rapidly than the Rhesus monkey and
appears to be more similar to man in the rate of PCP elimination.
It is difficult to draw reliable conclusions from most of the
previously reported human urinary excretion data, except for the
Braun, et al. (1978) study, for the following reasons: (1) the
exposures were accidental or occupational, with the quantity un-
known; and (2) the reports do not account for continued background
exposure.
018
-------
TABLE 6
Pharmacokinetics of PGP in Rats Given
Single Oral Dose of 10 mg/kg*
Parameter
K (hr'1)
e
K12 (hr'1)
K21 (hr~1)
^(hr'1)
^(hr'1)
t*s ( «8>O (hr)
t% (ft } (hr)
Vx (ml/kg)
Males
0.0343
0.0046
0.0061
0.0398
0.0173
17.4
40.2
136
Females
0.0478
0.0032
0.0100
0.0518
0.0213
13.4
32.5
127
*Source: Braun, et al. 1977
C-19
-------
There is speculation that there may be long-term tissue bind-
ing and limited storage of PCP. This has resulted from considera-
tion of the long-term fat storage of chlorinated hydrocarbon insec-
ticides such as DDT and dieldrin and the inference that PCP may act
accordingly. The other factor generating this speculation is based
on the study by Casarett, et al. (1969) , where urine and blood of
occupationally exposed workers were analyzed for PCP. Casarett
observed a decline in urine and blood PCP levels in workers during
vacation periods when the individuals were not occupationally ex-
posed. However, the urine PCP levels did not decline to zero.
Other studies by Casarett, et al. (1969), Bevenue, et al. (1967a),
and Kutz, et al. (1968) report finding low levels of PCP in the
urine of nonoccupationally exposed individuals. The Casarett study
of occupationally exposed workers did not measure PCP exposure dur-
ing the vacation period. Consequently, the levels observed during
the vacation period could represent evidence of long-term tissue
binding or continuing background exposure. Long-term, low level
tissue binding has not been adequately studied.
EFFECTS
Acute, Subacute, and Chronic Toxicity
Pentachlorophenol solutions can cause skin irritation. Immer-
sion of hands for 10 minutes in a 0.4 percent solution of PCP can
cause pain and inflammation (Bevenue, et al. 1967a).
Dust and mist concentrations greater than 1.0 mg/m cause
painful irritation in the upper respiratory tract accompanied by
violent sneezing and coughing in persons newly-exposed to PC?.
Concentrations as high as 2.4 mg/m^ can be tolerated by conditioned
individuals (AIHA, 1970) .
C-20
-------
The oral lethal dose of PCP in several species of animals
ranges from 70 to 300 mg/kg (Bevenue and Beckman, 1967; Deichmann,
et al. 1942). The mechanism of action involves the uncoupling of
oxidative phosphorylation (Weinbach and Garbus, 1965). Fuel oil-
type solvents reduce the lethal dose, while aqueous solutions of
the sodium salt are less toxic.
PCP exposure has resulted in death in man through occupational
and accidental exposures and suicide attempts (Gordon, 1956; Berg-
ner, et al. 1965; Armstrong, et al. 1969). Symptoms following
fatal exposures include general weakness, fatigue, dizziness, head-
ache, anorexia, profuse sweating, nausea, vomiting, hyperpyrexia of
106 to 108 F, dyspnea, tachycardia, abdominal pain, terminal
spasms, and death three to 25 hours after onset of symptoms. Le-
sions include inflamed gastric mucosa, pulmon-ary congestion, pul-
monary edema, fatty metamorphosis of the liver, and degeneration of
renal tubules and myocardium.
Nonfatal acute exposure can result in skin irritation, nasal
and respiratory tract irritation, sneezing and coughing, and eye
irritation.
One unique poisoning episode involved babies wearing diapers
rinsed in an antimicrobial laundry neutralizer containing sodium
pentachlorophenate. Babies wearing the diapers an average of eight
days became ill and some died. Some were less severely affected
and recovered spontaneously (Armstrong, et al. 1969; Pobson, et al.
1969) . Six of the nine severely affected had hepatomegaly and two
of the nine had splenomegaly in addition to profuse sweating hvner-
pyrexia.
C-21
-------
A review of the U.S. EPA Pesticide Episode Response Branch
report of September 14, 1976, revealed 47 cases of human exposures
ranging from direct eye contact to more serious intoxications in-
volving systemic effects. Significant cases included five situa-
tions where PCP was used inside homes and resulted in headache, eye
irritation, dyspnea, malaise, and in one case chronic weight loss
(U.S. EPA, 1976) .
One chronic health effect associated some years ago with cer-
tain types of commercial PCP exposure is chloracne, a type of acne-
form dermatitis similar to juvenile acne. It is characterized by
folliculitis and comedones with secondary infections. Chloracne
results from exposure to a variety of substances including chlori-
nated biphenyls, chlorinated naphthalenes, and tetra- and hexachlo-
rodioxins. Baader and Bauer (1951) reported acne, skin, and respi-
ratory tract irritation in workers in a German plant producing PCP
from HC3. In addition, eight of ten workers reported pain of the
lower extremities that occurred with the onset of the chloracne.
Nomura (1953) reported two cases of acneform skin eruptions in
workers in a PCP plant in Japan. It was not reported whether the
PCP was produced from HCB or by the chlorination of phenol.
Johnson, et al. (1973) found that commercial PCP containing
higher levels of chlorodioxins produced chloracne in the rabbit ear
test. Using pure PCP or PCP with reduced dioxin content did not
cause chloracne.
Symptoms in chronic toxicity, in general, are similar to those
seen in acute intoxications. PCP does not accumulate in body tis-
sues to the extent of the chlorinated hydrocarbon insecticides such
C-22
-------
as DDT and dieldrin. Consequently, chronic intoxications result
from relatively high levels of continuous exposure. Symptoms in
nonfatal chronic exposures include muscle weakness, headache, ano-
rexia, abdominal pain, and weight loss in addition to skin, eye,
and respiratory tract irritation.
A group of v/ood treaters in Hawaii has been studied medically
for a number of years. Physiopathologic changes were minimal.
Klemmer (1972) noted that the levels of the serum enzymes SCOT,
SGPT, and LDH were highest in the occupationally exposed group, but
were still within normal limits.
Workers chronically exposed to ?CP demonstrated significantly
elevated levels of total bilirubin and creatinine phosphokinase,
although the levels were within normal limits. Workers chronically
exposed to PGP showed a significantly higher—prevalence of gamma
mobility C-reactive protein (CRP) in the sera. The clinical sig-
nificance of these elevated levels of CRP in individuals exposed to
PCP is not known. CRP levels are often elevated in acute states of
various inflammatory disorders or tissue damage (Takahashi, et al.
1976) .
Begley, et al. (1977) determined plasma and urine PC?, renal
creatinine, phosphorus clearance, and phosphorus reabsorption in 19
workers before and after a 20-day vacation. Plasma PCP decreased
from 5.14 to 2.19 mg/1 at the end of the vacation. Following vaca-
tion, both the depressed creatinine clearance values and the phos-
phorus reabsorption values improved.
Caution is required in interpreting the human epidemiological
data since some of the occupationally exposed group were exposed to
other wood-preserving chemicals and solvents.
C-23
-------
Chronic animal studies have been reported which aid in the
evaluation of long term health effects. A complicating factor in
such studies is the presence of varying amounts of nonphenolic con-
taminants in the PCP used in the various studies. Some of the ef-
fects are related to the nonphenolic constituents. Oral doses of 1
and 3 mg technical PCP/kg for 90 days did not produce signs of
intoxication in rabbits (Machle, et al. 1943).
Male and female rats fed 25 ppm (equivalent to 1.5 mg/kg)
technical PCP for 12 weeks did not show significant toxic effcts.
A level of 50 ppm (approximately 3 mg/kg) resulted in decreased
hemoglobin and RBC numbers in male, but not female, rats. A level
of 200 ppm (approximately 12.5 mg/kg) increased liver aniline
hydroxylase activity in male and female rats and decreased hemoglo-
bin and RBC numbers in male rats (Knudsen, et al. 1974).
Goldstein, et al. (1977) fed rats 20, 100, or 500 pom techni-
cal and pure PCP (equivalent to 1.2, 6, and 30 mg/kg, respectively)
for eight months. At 20 ppm, liver aryl hydrocarbon hydroxylase
and glucuronyl transferase were increased in female rats fed tech-
nical PCP as compared to controls fed pure PCP. At 100 ppm techni-
cal PCP increased excretion of uroporphyrin and delta-aminolevulin-
ic acid. Feeding 20 or 100 ppm of pure PCP had no effect. Body
weight gain was reduced at 500 pom with both types of PCP. The no-
observable-adverse-effeet-level (NOAEL) for pure PCP from this
study was 6 mg/kg (i.e., the 100 ppm diet group).
Kociba, et al. (1971) compared the toxicity of purified versus
technical grade PCP. In their study, rats were fed either 3, 10, or
30 mg technical grade or purified PCP/kg body weight/day. They
C-24
-------
noted a relative increase in liver weight at all three dosages of
the technical PCP, but only at the 10 and 30 mg/kg dosages of puri-
fied PCP sample. The technical grade also caused an increase in
the absolute liver weights at the 10 and 30 mg/kg dosages, while in
the pure sample this was observed at only the 30 mg/kg dosage. In-
creased relative kidney weights were found at all three dosage lev-
els in the technical grade recipients, while this was noted only at
the 30 mg dosage level of the purer sample. Increased absolute
kidney weights were found at the top dosage level (30 mg/kg) of the
technical grade sample, but this alteration was not noted at any
dosage level of the purified sample. No other organ weight altera-
tions were considered to be related to treatment. In the same
study, these investigators observed no gross toxicologic effects in
the groups of animals fed 3 and 10 mg purified PCP/kg/day. Minimal
focal hepatocellular degeneration and necrosis were observed upon
microscopic examination of liver from animals maintained on the top
dosage level of technical grade PCP. These changes were not ob-
served in animals maintained on a diet containing the purified PCP
which provided a similar dosage of PCP.
Toxicological effects observed by Kociba, et al. (1971) in the
rats receiving the technical grade PCP sample were as follows:
slight increases in preterminal hemoglobin levels, packed cell vol-
umes and total erythrocytes, and elevated serum glutamic-pyruvic
transaminase activity with minimal focal hepatocellular degenera-
tion and necrosis at the 30 mg/kg/day dosage level; decreased serum
albumin levels at the 10 and 30 mg/kg/day dosage level; and slight-
ly elevated levels of serum alkaline phosohatase activity at all
:-25
-------
three dosage levels. Purified PCP was believed to have minimal
toxicological properties at the levels used in this feeding study.
Kociba, et al. (1971) concluded that the observed treatment-
related alterations, which were more evident in rats maintained on
diets containing the technical grade sample than those receiving
similar levels of the purified sample, could be attributed to some
degree to the presence of nonphenolics, chlorinated dibenzo-p-
dioxins, and dibenzofurans in the technical sample (Dowicide 7^ .
In a similar supportive study, Johnson, et al. (1973) reported
that male rats fed diets containing 10 and 30 mg/kg/day and females
receiving 30 mg/kg/day of the test material underwent minimal in-
creases in liver weights which were more apparent in the male than
in the female rats. In males, both the absolute and body weight-
relative liver weights were increased, while only the relative
weight was increased in the females. Minimal increases in kidney
weights were observed in both males and females receiving only the
30 mg/kg dosage of technical grade PCP. In the male rats, both the
absolute and body weight-relative kidney weights were increased,
while in the females only the relative weight was increased. MO
other alterations in terminal body and organ weights were consid-
ered related to treatment. Gross and microscopic examinations of
rats and tissues, respectively, revealed no lesions related to
treatment. Although some tissue lesions were observed in the 30
mg/kg/day rats, those lesions were considered spontaneous in nature
and unrelated to treatment.
In a 12-week chronic study, Knudsen, et al. (1974) fed wean-
ling rats 0, 25, 50, and 200 mg PCP/kg diet. The serum alkaline
C-26
-------
phosphatase activity was found to be significantly hiqher in the 25
and 200 mg/kg groups. A relative increase in liver weight was ob-
served at the 200 mg/kg (both sexes) and 50 mg/kg (females only)
doses. No other significant dose-related effects were observed in
the animals fed 25 mg PCP/kg diet in this 90-day study.
Kociba, et al. (1973) fed rats 1, 3, 10, or 30 mg/kg of a PCP
containing low amounts of nonphenolic impurities for 90 days. The
no-effect level was 10 mg/kg in females and 3 mg/kg in males. The
effect in males at 10 mg/kg was limited to a change in liver weight.
There were no treatment-related histopathologic changes.
The NOAEL in Sprague-Oawley rats fed a PCP containing low
amounts of nonphenolic impurities for 22 to 24 months was 3 mg/kg
in females and 10 mg/kg in males (^chwetz, et al. 1978). The feed-
ing levels were 1, 3, 10, or 30 mg/kg. The highest dose (30 mg/kg)
resulted in decreased body weight gain, increased SGPT, and in-
creased urine specific gravity.
Teratogenicity
Information on teratogenic studies is limited. No information
was encountered suggesting pentachlorophenol is a human teratogen.
Hinkle (1973) found fetal deaths and/or resorptions in three
of six test groups using Golden Syrian hamsters. Dose-response
data and statistical analysis were not provided. nose range was
from 1.25 to 20 mg/kg.
A single 60 mg/kg dose on day 9 or 10 of gestation reduced
fetal weights in Charles River CD strain rats, but had no effect
when given on days 11, 12, or 13. A total of four abnormalities out
of 97 fetuses were found. One of 46 fetuses from day 8 exposure was
0-27
-------
a dwarf, and 3 of 51 fetuses from day 9 exposure had malformations
consisting of exencephaly, macropthalmia and taillessness. No
skeletal abnormalities were found. An increase in maternal deep
body temperature of 0.5 to 0.8°C was reported, which indicates sys-
temic toxicity. A dose of 60 mg/kg is about 75 percent of the LD
The authors concluded that the number of malformations was minimal
and could have been due to toxic effects on the maternal rat
(Larsen, et al. 1975).
Schwetz, et al. (1974) provided more complete data from a rat
study using purified and commercial grade PCP. Dosages ranged from
5 to 50 mg/kg daily and exposure was during days 6 to 15 of gesta-
tion. The NOAEL based on incidence of fetal resorption was 5.8
mg/kg (adjusted dose to provide 5 mg PCP/kg) for commercial and 15
mg/kg for purified grade PCP. At 50 mg purified PCP/kg fetal re-
sorption was 100 percent, ^he NOAEL level for reducing fetal body
weight was 15 mg/kg for both grades. Fetal anomalies consisting of
subcutaneous edema and dilated ureters were observed in soft tis-
sues at doses of 15 mg/kg or above for both grades of PCP. The
NOAEL for soft tissue anomalies was 5 mg commercial grade PCP/kg/
day. Delayed ossification of the skull was noted at 5 mg/kg with
purified PCP. The NOAEL for skeletal anomalies with commercial PCP
was 5.8 mg/kg. At higher dosages, skeletal anomalies consisted of
lumbar spurs, supernumerary or fused ribs, or supernumerary, abnor-
mally shaped, missing, or unfused centers of ossification of verte-
brae or sternebrae. These effects were more readily produced when
dosing occurred on days 8-11 rather than days 12-15 of gestation.
The authors considered the effects by PCP to be evidence of embryo-
toxicity and fetotoxicity, not teratoqenicitv.
r-28
-------
Schwetz, et al. (1978) also reported a reproduction study.
Male and female rats were fed 0, 3, or 30 mg PCP/kg for 62 days
before mating, during 15 days of mating, and during gestation and
lactation. No evidence of toxicosis in the males was reported.
The females on the highest dose gained less weight. The 3 rr.g/kg
dose was the NOAEL. At 30 mg/kg the following indices were de-
creased: percentage of liveborn pups; 7, 14, 21 day post-birth
survival; 1, 7, 14, 21 day pup body weight; and 7, 14, 21 day litter
size. Since the LD5Q of PCP in 3- to 4-day-old rats is 65 mg/kg
compared to 150 mg/kg in adult rats, the observed effects on off-
spring may be the result of fetal toxicity.
Mutagenic ity
Sodium PCP was not mutagenic to male germ cells of Drosophila
when tested at a concentration of 7 mM (Vogel—and Chandler, 1974).
PCP was not mutagenic in the mouse host-mediated assay or in ir\
vitro spot tests (Buselmaier, et al. 1973).
Anderson, et al. (1972) also reported that PC? did not produce
mutagenic effects when tested _in vitro using histidine-requiring
mutants of Salmonella typhimuriurr. as the test organism. The purity
of the PC? used in the three studies cited was not specified.
Fahrig, et al. (1978) tested recrystallized PCP in two muta-
genic test systems. In the first system Saccharomvces cerevisiae
was used. The PCP concentration used was 400 mg/1, which resulted
in a 59 percent survival of test organisms and increased the fre-
quency of mutations and mitotic gene conversion compared to con-
trols. In the second system change in hair coat color (spots) in
mice was studied by injecting dams on the tenth day of aestation
r> "»Q
v - J- t
-------
with an intraperitoneal dose of either 50 or 100 mg/kg. Four out of
473 offspring were reported to have spots of genetic relevance.
Carcinogenicity
Dermal application of a 20 oercent solution of PCP dissolved
in benzene did not increase the rate of oapillomas in mice pre-
treated with dimethylbenzanthracene (DMBA) (Boutwell and Bosch,
1959) . The initiator (DMBA) was applied once and the pentachloro-
phenol applied twice weekly for 15 weeks. Seven percent of the
controls and 4 percent of the PCP group developed papillomas. Nei-
ther group developed carcinomas. The exposure rate was 5 mg PCP
per treatment applied in one drop to an unspecified skin area.
Mice dosed with commercial PCP at 46.4 mg/kg from 7 to 28 days
of age, and then fed 130 ppm PCP in the diet for the remainder of
their life span (approximately 18 months), did not have a signifi-
cant increase in tumors (Innes, et al. 1969). Detailed results
were not published. The study used 18 male and female mice of each
of two strains for a total of 72 mice.
PCP containing low amounts of nonphenolic impurities was non-
carcinogenic when male and female Sprague-Dawley rats were fed 0,
1, 3, 10, or 30 mg/kg for 22 months (males) or 24 months (females)
(Schwetz, et al. 1978). Each sex dose group contained 25 animals.
The results, summarized in Table 7, reveal no evident rlose-response
relationship. (In this study, a NOAEL based on clinical chemistry
and hematology determinations, routine histopathology, and organ
weight changes was determined to be 3 mg/kg in females and 10 mg/kg
in males. The NOAEL of 3 mg/kg was used to calculate the toxicity-
based criterion shown later in this document.)
C-30
-------
TABLE 7
Incidence of Primary Tumors (Based on Histopathological Diagnosis) in Rats Fed
Pentachlorophenol (PCP) for 22 Months (Males) and 24 Months (Females)*
Dose: mgPCP/kg/day
Number of rats
examined:
Number of rats
with tumors:
o
tl; Number of tumors:
Number of tumors/
rats with tumors:
Number of morphologic
malignant tumors:
0
27
11
17
1.6
1
1
26
13
14
1.1
3
Males
3
27
13
17
1.3
2
Females
10
27
12
15
1.4
1
30
27
11
61
2.3
0
0
27
27
62
2.6
2
1
27
26
67
1.7
7
3
27
25
42
1.7
2
10
27
25
63
2.5
3
30
27
25
63
2.5
2
*Source: Schwetz, et al. 1978
-------
Other Effects
An organoleptic threshold for pentachlorophenol in water has
been reported by at least two investigators. Hoak (1957) reported
the odor threshold of phenol and 19 phenolic compounds. In a study
conducted at the Mellon Institute in Pittsburgh, Pennsylvania, a
panel of two or four persons sniffed samples of pure phenolic com-
pounds in odor-free water, which had been heated to either 30 or
60 C. A flask of plain odor-free water was provided for compari-
son. The various samples were placed in random order before the
test persons, and the flask with the lowest perceptible odor was
noted by each individual sniffer. The lowest concentration detect-
ed was considered to be the threshold. Chlorinated phenols were
the compounds most easily detected. The odor thresholds for PCP at
30 and 60°C were 857 yg/1 and 12,000 uq/1, respectively. Hoak had
speculated that odor should become more noticeable as temperature
increases; however, when a series of chlorophenols and cresols were
evaluated, it was found that some compounds had higher odor thresh-
olds at 30°C, while others had higher thresholds at 60°C.
Dietz and Traud (1978) used a panel composed of 9 to 12 per-
sons of both sexes and various age groups to test the organoleptic
detection thresholds for 126 phenolic compounds. To test for odor
thresholds, 200 ml samples of the different test concentrations
were placed in stoppered odor-free glass bottles, shaken for ap-
proximately five minutes, and sniffed at room temperature (20-
22°C). For each test, water without the phenolic additive was used
as a background sample. The odor tests took place in several indi-
vidual rooms in which phenols and other substances with intense
C-32
-------
odors had not been used previously. Geometric mean values were
used to determine threshold levels. To determine taste threshold
concentrations of selected phenolic compounds, a panel of four test
individuals tasted water samples containing various amounts of phe-
nolic additives. As a point of comparison, water without phenolic
additives was tasted first. Samples with increasing phenolic con-
centrations were then tested. Between samples, the mouth was
rinsed with the comparison water and the test person ate several
bites of dry white bread to "neutralize" the taste. Geometric mean
detection level values for both tests provided threshold levels of
30 yg/1 for taste and 1,600 yg/1 for odor for the chemical penta-
chlorophenol.
Neither of these studies, however, indicated whether the
determined threshold levels made the water undesirable or unfit for
consumption.
C-33
-------
CRITERION FORMULATION
Existing Guidelines and Standards
The maximum air PCP concentration established by the American
Industrial Hygiene Association (1970) is 0.5 mg PCP or 0.5 mg
NaPCP/m for an 8-hour exposure (TLV). The Code of Federal Regula-
tions 21, part 121, paragraph 121:2556 allows up to 50 ppm PCP in
wood used in contact with food.
A tolerance for PCP in food has not been established.
A no-adverse-effect-level in drinking water of 0.021 mg PCP/1
is suggested by the National Research Council (1977). The recom-
mendation is based on a NOAEL of 3 mg/kg in the 90-day to 8-month
rat studies. A safety or "uncertainty factor" of 1,000 and a water
consumption of 2 I/day were used in arriving at the level.
Current Levels of Exposure
Based on an assumed food consumption of 1.5 kg/day and a water
intake of 2 I/day (2.0 kg), a food PCP residue of 10 yg/kg, and a
water PCP residue of 60 ng/kg, the resulting maximum total daily
exposure for a 70 kg person would likely be 15 yg from food and 120
ng from water. The exposure rate would be 0.21 ug/kq/day from food
and 1.7 ng/kg/day from water. The estimated food residue level (15
ug) is higher than the 1 to 6 yg/day intake calculated by Manske and
Corneliussen (1974) where the calculations took into consideration
dietary consumption by food class.
An alternative approach to estimating human exposure is extra-
polation from urine residue data, since PCP is primarily eliminated
in the urine, and at equilibrium excretion equals dailv intake. In
Hawaii, where exposure for the general population may be higher
C-34
-------
than that for persons living in colder climates due to differences
in the use of PGP-treated wood in home construction/ Bevenue, et
al. (1967a) reported an average PGP urine value of 40 ug/1. Assum-
ing a daily urine void of 1.4 1 the total daily PGP excretion would
be 56 ug, an amount equal to the intake. Cranmer and Freal (1970)
found an average of 5.8 ug/1 in six general population urine sam-
ples, and Kutz, et al. (1978) reported an average of 6.3 ug/1 for
416 samples. Consequently, location of residence may influence PGP
exposure. Based on available data, the exposure for the general
population is estimated to range from 1 to 50 ug/person/day.
Exposure will increase sharply if an individual works with the
material and inhales vapors (Casarett, et al. 1969) and/or experi-
ences dermal absorption (Bevenue, et al. 1967a). Casarett, et al.
(1969) studied two subjects working in a room in which PGP is ap-
plied by brush to lumber and found that the urine PGP concentration
peaked at 30 to 50 ug/1.
Occupationally exposed individuals excrete more PGP in the
urine than do persons from the general population. Reported urine
values include an average of 1.8 mg/1 for 130 pest control opera-
tors (Bevenue, et al. 1967b), 1 to 10 mg/1 for wood treaters (Casa-
rett, et al. 1969), 2.8 mg/1 for dip treaters, 0.98 mg/1 for spray
treaters, and 1.24 mg/1 for pressure treaters (Arsenault, 1976).
Using the same assumption of 1.4 1 of urine per day, the estimated
occupational exposures would range from 1.37 to 14 mg/person/day.
Special Groups at Risks
Two groups can be expected to encounter the largest exposures.
One group consists of employees involved in the manufacture of PGP;
G-35
-------
this cohort is presently under industrial health surveillance pro-
grams.
The second and larger group is comprised of formulators and
wood treaters. Exposure, hygiene, and industrial health practices
can be expected to vary from the small wood treaters to the larger
companies. Health related data in general are not available for
this group. Employees of two Hawaii wood-treating companies have
been studied for a number of years, and although exposures have
resulted in blood and urine levels of 1 to 10 mg/1, adverse health
effects have been minimal.
Basis and Derivation of Criterion
Based on available and cited literature, PC? is not considered
to be carcinogenic.
A health effects criterion can be calculated using the data
from the chronic toxicity studies. Using a NOAEL of 3 mg/kg
(Schwetz, et al. 1978) for purified PC? containing only low amounts
of nonphenolic impurities and applying a 0.01 animal-to-human un-
certainty factor, the upper limit for nonoccupational daily expo-
sure is 0.03 mg/kg or 2.10 mg/70 kg person. Satisfactory 90-day
(Kociba, et al. 1973) and 22 to 24 month (Schwetz, et al. 1978)
studies have defined both a NOEL and a NOAEL, respectively, based
on micropathologic effects and biochemical indices. These data, in
addition to the limited available human data, justify the selection
of a safety factor of 100.
For the purposes of calculating a water quality criterion,
human exposure to PCP is considered to be based on daily inqestion
of 2 liters of water and 5.5 q of fish. The amount of PCP contained
C-36
-------
in ingested water is approximately 100 times greater than the
amount of PCP in consumed fish. However, fish bioaccumulate PCP
from water by a factor of 11 and thus contain about half as much PC?
per gram as water.
With these considerations in mind, the following equation has
been established:
(2 1 C) + (0.0065 11 C) = ADI = 2.10 rag
where:
2.10 mg = acceptable daily intake (ADI) for a 70 kg person
21= amount of drinking water consumed daily
0.0065 kg = amount of fish consumed daily
11 = bioconcentration factor
Solving for C, the water quality criterion, gives:
C = 1.01 mg/1
This criterion can alternatively be expressed as 29.4 mg/1 if
exposure is from consumption of fish and shellfish only.
Present residues of PCP are reported to be 0 to 10 ug/kg in
food, and one report indicates 0.06 yg/kg in water. These levels
are well below the above criterion, and total daily general popula-
tion exposures are less than 1 percent of the calculated maximum
value based on toxicologic considerations.
It should be noted that this calculated toxicity criterion is
based on a NOAEL for a purified grade PCP containing onlv low
amounts of nonphenolic compounds. PCP containing low amounts of
nonphenolic impurities has been found to be noncarcinogenic at the
dosages tested. However, NCI is presently conducting studies on
the carcinogenicity of the PCP contaminants hexachlorodibenzo-p-
C-37
-------
dioxin and octachloro-p-dioxin, the results of which are not yet
available. The results of these studies should be evaluated before
any EPA regulatory standards are established. It should be noted,
however, that criteria presented in this document are recommended
levels for the pure compound only and not for any contaminants or
metabolites of PGP.
Since the taste and odor detection threshold concentrations
for pentachlorophenol are below the derived toxicity-based criteri-
on level, the ambient water quality criterion is based on organo-
leptic data. It should be emphasized that this criterion is based
on aesthetic qualities rather than health effects. However, to the
extent that this criterion is below the level derived from the
chronic toxicity studies of Schwetz, et al. (1978) and Kociba, et
al. (1973), it is likely to also be protective^of human health.
The data of Hoak (1957) and Dietz and Traud (1978) indicated
that high microgram concentrations of pentachlorophenol in water
are capable of producing a discernable odor. Neither of these
studies indicated a range of responses, but it is certainly possi-
ble that at least some of the "sniffers" in the Dietz and Traud
group could detect concentrations of PCP down near the 857 yg/1
value of Hoak; similarly, it is possible that some of the "sniff-
ers" in the Hoak group would be able to initially detect the pres-
ence of PCP at concentrations near the geometric mean threshold
value of Dietz and Traud. Dietz and Traud (1978) further observed
a distinct flavor alteration of water at low microgram levels of
PCP. The taste threshold (30 ug/1) determined by Dietz and Traud
for PCP in water is used to arrive at the criterion level for this
chemical.
C-38
-------
Therefore, based on the prevention of undesirable organoleptic
qualities, the criterion level for pentachlorophenol in water is 30
yg/1. This level should be low enough to prevent detection of
objectionable organoleptic characteristics by most people and far
below minimal no-effect concentrations determined in laboratory
animals.
:-39
-------
REFERENCES
Ahlborg, U.G. 1978. Dechlorination of Pentachlorophenol in vivo
and ir\ vitro. In; K. Rango Rao (ed.), Pentachlorophenol: Chemis-
try, Pharmacology, and Environmental Toxicology. Plenum Press, New
York. p. 115.
Ahlborg, U.G., et al. 1974. Metabolism of oentachlorophenol.
Arch. Toxicol. 32: 271.
American Industrial Hygiene Association. 1970. ^ygienic guide
series: Pentachlorophenol and sodium pentachlorophenate. Am. Ind.
Hyg. Assoc. Jour. 31: 521.
Anderson, K.J., et al. 1972. Evaluation of herbicides for oossi-
ble mutagenic properties. Jour. Agric. Food Chem. 20: 649.
Armstrong, R.W., et al. 1969. Pentachloroohenol poisoning in a
nursery for newborn infants. II. Epidemiologic and toxicologic
studies. Jour. Pediatr. 75: 317.
Arsenault, R.D. 1976. Pentachlorophenol and contained chlorinated
dibenzoidioxins in the environment: A study of environmental fate,
stability, and significance when used in wood preservation. Pre-
sented at the American Wood-Preservers' Assoc. Annu. Meet., At-
lanta, Georgia, April 25-28. p. 1.
C-40
-------
Baader, E.W. and H.J. Bauer. 1951. Industrial intoxication due to
pentachlorophenol. Ind. Med. Surg. 20: 286.
Begley, J. , et al. 1977. Association between renal function tests
and pentachlorophenol exposure. Clin. Toxicol. 1: 97.
Bergner, H., et al. 1965. Industrial oentachloroDhenol poisoning
in Winnipeg. Can. Med. Assoc. Jour. 92: 448.
Bevenue, A. and H. Beckman. 1967. Pentachlorophenol: A discussion
of its properties and its occurrence as a residue in human and ani-
mal tissues. Residue Rev. 19: 83.
Bevenue, A., et al. 1967a. A note on the effects of a temporary
exposure of an individual to pentachlorophenol. Bull. Environ.
Contam. Toxicol. 2: 293.
Bevenue, A., et al. 1967b. A survey of oentachloroDhenol content
in human urine. Bull. Environ. Contam. Toxicol. 2: 319.
Boutwell, R.K. and K.K. Bosch. 1959. The tumor-promoting action
of phenol and related compounds for mouse skin. Cancer Res.
19: 413.
Braun, W.H. and M.W. Sauerhoff. 1976. The pharmacokinetic profile
of pentachlorophenol in monkeys. Toxicol. Appl. Pharmacol.
38: 525.
C-41
-------
Braun, W.H., et al. 1977. The pharmacokineti.es and metabolism of
pentachlorophenol in rats. Toxicol. Appl. Pharmacol. 41: 395.
Braun, W.H., et al. 1978. The metabolism/pharmacokinetics of pen-
tachlorophenol in man, and a comparison with the rat and monkey
model. Toxicol. Appl. Pharmacol. 45: 135.
Buhler, D.R., et al. 1973. Occurrence of hexachlorophene and pen-
tachlorophenol in sewage and water. Environ. Sci. Technol.
7: 929.
Buselmaier, et al. 1973. Comparative investigations of the muta-
genicity of pesticides in mammalian test systems. Mutat. Res.
21: 25.
Casarett, L.J., et al. 1969. Observations on Dentachloroohenol in
human blood and urine. Am. Ind. Hyg. Assoc. Jour. 30: 360.
Conklin, P.J. and F.R. Fox. 1978. Environmental Impact of Penta-
chlorophenol and Its Products - A Round Table Discussion. In; K.R.
Rao (ed.), Pentachlorophenol: Chemistry, Pharmacology, and Envi-
ronmental Toxicology. Plenum Press, New York. p. 393.
Cranmer, M. and J. Freal. 1970. Gas chromatographic analysis of
pentachlorophenol in human urine by formation of alkyl ethers.
Life Sci. 9: 121.
C-42
-------
Cretney, M.J. 1976. Pentachlorophenol death. Bull. T.I.A.P.T.
12:10. In; T.J. Haley, 1977. Human poisoning with pentachlorophe-
nol and its treatment. Ecotoxicol. Environ. Safety. (In press)
Deichmann, W., et al. 1942. Acute and chronic effects of penta-
chlorophenol and sodium pentacholorophenate upon experimental ani-
mals. Jour. Pharmacol. Exp. Therap. 76: 104.
Dietz, F. and J. Traud. 1978. Geruchs- und Geschmacks-Schwellen-
Konzentrationen von Phenolkorpera. Gas-Wasserfach. Wasser-Abwas-
ser. 119: 318.
Duggan, R.E. and P.E. Corneliussen. 1972. Dietary intake of pes-
ticide chemicals in the United States (III). June 1968-April 1970.
Pestic. Monitor. Jour. 5: 331.
Engst, R. , et al. 1976a. The metabolism of hexachlorobenzene
(HCB) in rats. Bull. Environ. Contam. Toxicol. 16: 248.
Engst, R., et al. 1976b. The metabolism of lindane and its metab-
olites gamma-2,3,4,5,6-pentachlorocyclohexene, pentachlorobenzene,
and pentachlorophenol in rats, and the pathways of lindane metabo-
lism. Jour. Environ. Sci. Health. 2: 95.
Fahrig, R. , et al. 1978. Genetic Activity of Chlorophenols and
Chlorophenol Impurities. In: K.R. Rao (ed.), Pentachlorophenol:
Chemistry, Pharmacology, and Environmental Toxicology. Plenum
Press, New York. p. 325.
C-43
-------
Goldstein, J.A., et al. 1977. Effects of pentachlorophenol on
hepatic drug-metabolizing enzymes and porphyria related to contami-
nation with chlorinated dibenzo-p-dioxins and dibenzofurans. Bio-
chem. Pharmacol. 26: 1549.
Gordon, D. 1956. How dangerous is pentachlorophenol. Med. Jour.
Aust. 2: 485.
Hansen, D.J. 1980. Memorandum to C.E. Stephan. U.S. EPA.
Hinkle, O.K. 1973. Fetotoxic effects of pentachlorophenol in the
Golden Syrian hamster. Toxicol. Appl. Pharmacol. 25: 455.
(Abst.)
Hoak, R.D. 1957. The causes of tastes and odors in drinking water.
Water Sewage Works. 104: 243.
Innes, J.R.M., et al. 1969. Bioassay of pesticides and industrial
chemicals for tumorigenicity in mice. A preliminary note. Jour.
Natl. Cancer Inst. 42: 1101.
14
Jakobson, I. and S. Yllner. 1971. Metabolism of C-pentachloro-
phenol in the mouse. Acta. Pharmacol. Toxicol. 29: 513.
Johnson, R.D. and D.D. Manske. 1977. Pesticides in food and feed:
Pesticide and other chemical residues in total diet samples (XI) .
Pestic. Monitor. Jour. 11: 116.
044
-------
Johnson, R.L., et al. 1973. Chlorinated dibenzodioxins and penta-
chlorophenol. Environ. Health Perspect. Exp. Issue. 5: 171.
Karapally, J.C., et al. 1973. Metabolism of lindane-14C in the
rabbit: Ether-soluble urinary metabolites. Jour. Agric. Food Chem.
21: 811.
Klemmer, H.w. 1972. Human health and pesticides - community pes-
ticide studies. Residue Rev. 41: 55.
Knudsen, I., et al. 1974. Short-term toxicity of pentachloroDhe-
nol in rats. Toxicol. 2: 141.
Kociba, R.J., et al. 1971. Results of 90-day toxicological study
in male rats maintained on diets containing production grade or
purified pentachlorophenol. November 24, 1971. DOW Chemical Co.,
Midland, Michigan.
Kociba, R.J., et al. 1973. Toxicological evaluation of rats main-
tained on diets containing pentachlorophenol sample XD-8108 OOL for
90 days. March 2, 1973. Chem. Biol. Section, Dow Chemical Co.
Kohli, j., et al. 1976. Contributions of ecological chemistry
CVII - fate of lindane-14C in lettuce, endives, and soil under out-
door conditions. Jour. Environ. Sci. Health Bull. 1: 23.
G-45
-------
Koss, G. and W. Koransky. 1978. Pentachlorophenol in Different
Species of Vertebrates after Administration of Hexachlorobenzene
and Pentachlorobenzene. In; K.R. Rao (ed.), Pentachlorophenol:
Chemistry, Pharmacology, and Environmental Toxicology. Plenum
Press, New York. p. 131.
Kutz, F.W., et al. 1978. Survey of Pesticide Residues and their
Metabolites in Urine from the General Population. In; K.R. Rao
(ed.), Pentachlorophenol: Chemistry, Pharmacology, and Environ-
mental Toxicology. Plenum Press, New York. p. 363.
Larsen, R.V., et al. 1975. Placental transfer and teratology of
Pentachlorophenol in rats. Environ. Lett. 10: 121.
Lui, H. and C.D. Sweeney. 1975. Hepatic metabolism of hexachloro-
benzene in rats. FEES Lett. 51: 225.
Machle, W., et al. 1943. Observations on the fate of oentachloro-
phenol in the animal organism. Jour. Ind. Hyg. Toxicol. 25: 192.
Manske, D.D. and P.E. Corneliussen. 1974. Pesticide residues in
total diet samples (VII). Pestic. Monitor. Jour. 8: 110.
Mason, J.F., et al. 1965. Pentachlorophenol poisoning: Report of
two cases. Jour. Forensic Sci. 10: 136.
C-46
-------
Mehendale, H.M., et al. 1975. Metabolism and effects of hexachlo-
robenzene on hepatic microsomal enzymes in the rat. Jour. Agric.
Food Chem. 23: 251.
National Research Council. 1977. Drinking Water and Health.
Natl. Acad. Sci., Washington, D.C.
Nomura, S. 1953. Studies on chlorophenol poisoning. Podo Kaguku
Jour. Sci. Labor. 29: 474.
Rapp, D.S. 1978. Industrial hygiene study: Pentachlorophenol
users' plants. Industrial Hygiene Laboratory, Health and Environ-
mental Research, Dow Chemical USA, Midland, Michigan. (Unpubl.)
Robson, A.M., et al. 1969. Pentachlorophenol poisoning in a nur-
sery for newborn infants. I. Clinical features and treatment.
Jour. Pediatr. 75: 309.
Schwecz, 3.A., et al. 1974. The effect of purified and commercial
grade pentachlorophenol on rat embryonal and fetal development.
Toxicol. Appl. Pharmacol. 28: 151.
Schwetz, B.A., et al. 1978. Results of Two-year Toxicity and Re-
production Studies on Pentachlorophenol in Rats. In: K.R. Rao
(ed.), Pentachlorophenol: Chemistry, Pharmacology, and Environ-
mental Toxicology. Plenum Press, New York. o. 301.
C-47
-------
Shafik, T.M. 1973. The determination of pentachlorophenol and
hexachlorophene in human adipose tissue. Bull. Environ. Contam.
Toxicol. 15: 57.
Stephan, C.E. 1980. Memorandum to J. Stara. U.S. SPA. July 3.
Takahashi, W. , et al. 1976. Acute phase proteins and pesticide
exposure. Life Sci. 19: 1645.
U.S. EPA. 1976. Summary of reported episodes involving pentachlo-
rophenol. Pesticide episode review system. Report No. 60. Sept.
14, 1976. Pestic. Episode Response Branch, Operations Div. Off.
Pestic. Programs.
U.S. EPA. 1980. Seafood consumption data analysis. Stanford Re-
search Institute International, Menlo Park, California. Final
report, Task 11, Contract No. 68-01-3887.
Vogel, E. and J.L.R. Chandler. 1974. Mutagenicity testing of
cyclamate and some pesticides in Drosophila melanogaster. Experi-
entia. 30: 621.
Weinbach, E.G. and J. Garbus. 1965. The interaction of uncoupling
phenols with mitochondria and with mitochondrial protein. Jour.
Biol. Chem. 240: 1811.
C-48
-------
Wyllie, J.A., et al. 1975. Exposure and contamination of the air
and employees of a pentachlorophenol plant, Idaho 1972. Pestic.
Monitor. Jour. 9: 150.
Yang, R.S.H., et al. 1975. Chromatographic methods for the analy-
sis of hexachlorobenzene and possible metabolites in monkey fecal
samples. Jour. Assoc. Off. Anal. Chem. 58: 1197.
C-49
------- |