EPA - 560/8-75-003
ENVIRONMENTAL HAZARD ASSESSMENT SERIES
CHLOROPHENOLS
FINAL REPORT
OFFICE OF TOXIC SUBSTANCES
ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D. C. 20460
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ENVIRONMENTAL HAZARD ASSESSMENT SERIES
CHLOROPHENOLS
This document is a preliminary draft. It has not been
formally released by EPA and should not at this stage be
construed to represent Agency policy. It is being circu-
lated for comment.on its technical accuracy and policy
implications.
Prepared by
Office of Toxic Substances
Environmental Protection Agency
Washington, D. C. 20460
September 1975
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PREFACE
Our society uses thousands of chemical substances for many
purposes. A large number of these are released into'the environ-
ment in varying quantities as production or handling losses, as
waste materials* or as a direct consequence of their intended or
unintended uses. Concern over the possible effects of these
chemica.ls has prompted the establishment of a program to review
data on the release, exposure, and effects of chemical substances
in order to assist in setting priorities for further study or
possible regulatory action. This program is conducted by the
Early Warning Branch of the Office of Toxic Substances.
It is not practical to perform detailed analyses on every
commercial chemical. Materials which come to the attention of the
program are initially screened with a simple literature search and
a limited number of candidate chemicals are selected for more
detailed study according to criteria that include volume of pro-
duction, manner of use, .market growth potential, exposure patterns,
detection in environmental samples, known toxic effects, and
functional or chemical relationships to chemicals already identi-
fied as serious environmental pollutants. The early warning
system which feeds the screening process uses diverse sources
including opinions of experts, referrals from other units of
government, reports in the scientific and trade literature,
predictive modelling, and public inquiries.
These hazard assessments are prepared from reviews covering
the subject substances supplemented by additional searches and
inquiries to obtain the most complete and recent information
available.. Only those data considered pertinent to an assessment
of environmental hazard are reported in this series.
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Although attempts have beeri made to use as complete an infor-
mation base as possible, additional information may be available or
may become available. Therefore, these assessments are subject to
revisions in light of any new data. The Office of Toxic Substances
would welcome any additional pertinent data in this regard.
This document presents the position of the Office of Toxic
Substances and does not necessarily represent an Agency consensus.
Nor does it represent commitment to further action by the Environ-
mental Protection Agency or any other organization. Mention of.
tradenames and identification of manufacturers of specific products
in this document are for purposes of clarity and specificity only.'
They do not constitute an endorsement of any product.
This report was written by Dr. Irving Gruntfest. The Environ-
mental Hazard Assessment Series is being prepared under the guidance
of Dr. Farley Fisher, Chief of the Early Warning Branch, Office of
Toxic Substances.
A review of the literature which preceded this assessment was
conducted for EPA by Dr. Philip Howard and Mr. Patrick Durkin of the
Syracuse University Research Corporation, Syracuse, New York. That
review is part of a report titled Preliminary Environmental Hazard
Assessment of Chlorinated Naphthalenes, Silicones, Fluorocarbons,
Benzenepolycarboxylates and Chlorophenols which is available through
the National Technical Information Service, Springfield, Virginia
22151 (NTIS accession number - PB-238 074/AS). The information in
the review has been supplemented by consultations with selected
knowledgeable individuals both in and outside of the Federal Govern-
ment. The assistance of Dr. Carroll Collier, Mr. John Shaughnessy,
Mr. Tom Adamcyk, Dr. Ralph Ross, and Mr. W. S. Woodrow of EPA; of
Mr. Philip Lewis of FDA, Mr. Max Gabis of OSHA, Mr. Michael Causey
of GSA, and Mr. Donald Mengle of the State of California Department
of Health was particularly useful.
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TABLE OF CONTENTS
PREFACE ' i
LIST OF TABLES ". iv
LIST OF FIGURES v
SUMMARY 1
CONCLUSIONS 4
I. GENERAL INFORMATION 5
Def i ni ti on 5
»
Chemical and Physical Properties 5
Commercial Production 8
General Patterns of Use 12
II. ENVIRONMENTAL EXPOSURE FACTORS, 13
III. INCIDENTS OF ENVIRONMENTAL DAMAGE 18
IV. TOXICOLOGY AND BIOLOGY 21
V. ANALYSIS AND MONITORING 26
VI. REGULATIONS • 27
BIBLIOGRAPHY • 29
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LIST OF TABLES
Table I Physical Properties of Commercially Important Chlo-
rophenols. ' 7
Table II Vapor Pressures and Concentrations of the Saturated
Vapors of tri-, tetra- and Pentachlorophenol 9
Table III Production of Chlorophenols and Related Products... 10
Table IV Chlorophenol Producers and Their Plant Locations
and Capacities 11
Table V Compilation of Date on the Degradation of Various
Chlorophenols '. 15
Table VI LD5 's of Various Chlorophenols and Sodium Chloro-
Phenates After a Single Oral Administration 22
Table VII Compilation of Data on the Biological Activity of
Various Chlorophenols ." 24
LIST OF FIGURES
Figure .1 Structural Formulae of the Six Commercially
.Significant Chlorophenols
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SUMMARY
The chlorop'henols are a class of synthetic organic chemicals used
as pesticides and chemical intermediates at a rate exceeding 100
million pounds per year. Like phenol, from which the compounds are
derived, the chlorophenols are all irritating and toxic substances and
must be handled with care. Because of their volatility and water
solubility, transport of chlorophenols in both water and air occurs.
In the manufacture and use of certain" chlorophenols, a reaction may
occur which leads to the formation of a class of chlorinated dibenzo-
dioxins which are among the most toxic substances known. Some of the
current concern for the environmental effects of the chlorophenols
centers on the occurrence of these dioxin contaminants.
The chlorophenols have access to the environment when they are
used directly as agricultural pesticides, when chlorophenol treated
materials, such as wood or paints, are used or discarded, and as a
result of accidental spills or the mismanagement of industrial efflu-
ents. Chlorophenols may be formed in the aquatic environment when
waters containing phenol are. chlorinated, they are among the degradation
products of widely used herbicides (2,4-D and 2,4,5-T) and an insecticide
(Lindane), and they have been noted as products of the metabolism of
chlorinated benzenes in mammals.
The decay of the pesticidal activity of PCP a few days or weeks
after application has been attributed to photo- and biodegradation
processes. However, more recent studies, following an accidental
spill, show that while PCP does indeed disappear from water, it is
persistent in sediments (relatively high levels were maintained for
one year). Biomethylation of PCP in sewage plants to form penta-
chloroanisole, which accumulates in fish tissue, is also suspected.
Extremely sensitive methods for the analysis of chlorophenols
have recently been developed (low ppb) but these have.not been system-
atically applied in monitoring programs. However, PCP is always found
in the blood and urine of occupationally'exposed individuals (up
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to- 35 ppm in the urine of Hawaiian field workers) and smaller amounts
are found in the urine of members of the general population in regions
in which PCP is used (up to 0.04 ppm). -More recently traces of penta-
chlorophenol have been found in the urine and semen of all members of
a group of college students with no known record of occupational expo-
sure (a few parts per billion). In several urban water supplies,
small amounts of di-, tri-, and pentachlorophenol have been observed,
e_.g_. 6 ppb of 2,4-dichlorophenol at Cincinnati.
During the past three decades 30 human deaths and many more
incidents of human indisposition have been attributed to exposure to
PCP. In each case of death,, recommended practices for use were not
observed (instructions regarding hazard, protective clothing, prompt
wash-ups). However, some human indispositions have been associated
with "normal" usage as a wood preservative. In addition, industrial
accidents, spills and reactor failures nave caused the death of domestic
animals,';.fish kills and rendered hundreds of acres .of land uninhabitable
for long periods of time.
The acute oral toxicity of the chlorophenols toward small mammals
varies among members of the class. The most toxic member (PCP) has an
LD5Q of 27 mg/kg in rats. The least toxic are the di- and trichloro-
phenols for which the LD5Q exceeds 2 g/kg. In a recent long-term
feeding study using rats it was shown that at low levels (up to 500
ppm in the diet), purified PCP was less toxic than technical grade
material which contained 0.2% of chlorinated dibenzodioxins. Liver
damage and other profound physiological changes have been noted as
having been caused by the exposure of laboratory animals to pentachlo-
rophenol but, for the most part, the purity of the material tested was
not discussed. Fish are particularly sensitive to chlorophenols,
particularly PCP for which TLm = 0.05 ppm in water. Simple plants and
microorganisms are also very sensitive to chlorophenols and this
accounts for much of the commercial utility of these materials.
Carcinogen!city and co-carcinogenicity toward mice has been
demonstrated for members of the class and recent studies show that
pentachlorophenol is mutagenic toward certain bacteria.
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Two members of the class, tri-"and pentachlorophenol, are EPA-
registered pesticides and have FDA-approved uses, in food packaging
3
materials. A tolerance limit of 0.5 mg/m for PCP in air has been set
by the American Conference of Government Industrial Hygienists. None
of the chlorophenols are named in the EPA Guidelines for'industrial
effluents, but tri- and pentachlorophenol have been designated as
hazardous materials in proposed EPA rules governing the control of
accidental spills. Products, such as wood, that contain chlorophenol
preservatives are not now regulated.
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CONCLUSIONS
1. Low concentrations of certain chlorophenols are now widely dis-
tributed in the environment as a result of their large scale
production and use and because of their inadvertant generation
from other chemicals.
2. Existing regulations have not been completely effective in elimi-
nating incidents of damage due to the production.and use of chlo-
rophenols.
3. The long-term environmental fate and effects of the chlorophenols
are not completely understood but liver damage is produced in
mammals and there is evidence that some members of the class are
carcinogens
4. No systematic programs for monitoring chlorophenols in the envi-
ronment are now in place.
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I. GENERAL INFORMATION
Definition
Any of a large number of organic compounds in which a hydroxyl
group is attached to an aromatic ring and which contain chlorine might
be called a chlorophenol and many of these are articles of commerce.
However, in this document only simple chlorophenols, which have a
single benzene ring carrying a single hydroxyl group and having no
substituents other than chlorine, are -considered. The compounds so
defined constitute a class having 19 members. Six of these are known
to be produced in commercial quantities for use as pesticides and
chemical intermediates.
The general empirical formula of the simple chlorophenols is
CgH/exOCl in which x ranges from 1 to 5. There-are three distinct
isomeric monochlorophenols (x=l) commonly designated as ortho-, meta-,
and para-chlorophenol. These designations are usually abbreviated to
o^-, rn-, and p_-chlorophenol; alternatively these three materials can be
called 2-chloro-, 3-chloro-, and 4-chlorophenol, respectively.
/
Similarly, there are six distinct isomeric dichlorophenols; six tri-
chlorophenols, three tetrachlorophenols and one pentachlorophenol.
The structural formulae and chemical names of the six commercially
important simple chlorophenols are shown in Figure 1.
Chemical and Physical Properties
The chemistry of the chlorophenols is somewhat similar to that of
the "parent" compound, phenol, which is one of the major products of
the organic chemical industry. The simple chlorophenols have limited
solubility in water, but, being acidic, they form .salts and become
soluble in aqueous base. The acid strengths of the chlorophenols,
which determine the pH at which they become soluble, increase with
the number of chlorine atoms in the molecule. The dissociation con-
stants of the commercial materials are. shown, along with some of their
^
other properties, in Table I.
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•Figure 1
STRUCTURAL FORMULAE OF THE SIX COMMERCIALLY
SIGNIFICANT CHLOROPHENOLS .
4-chlorophenol
p-chlorophenol
OH
Cl
2,4-dichlorophenol
OH
Ci ';
2,4,6-trichlorophenol
CI
2,4,5-trichlorophenol
CI
Cl
2,3,4,6-
tetrachlorophenol
penta-
chlorophenol (PCP)
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TABLE I
Physical Properties of Commercially Important Chlorophenols
(Doedcns, 1964; Bcvenuc and Becknan, 1967)
i *^"---*^^ Compound
Propcrtv ^"""^•^•^^
( Melting point ("C)
!
1 Boiling point (*C)
1
( Dissociation
constant (K )
i at 25'C 3
i
Solub-ility (g/lOOg)
Water (25*C)
Temperature ac
which the vapor
pressure equals
; lm,Hg
Vchloro-
?henol
40-41
219
6.6xlO-10-
2.71
49.8
2,i-(iichloro-
phenol
43-44
210-211
2.1xlO"8
slight
53.0
2,4,6-tri-
chloro-
phenol
68
246
3.8xlO"8
insol.
76.5
2,4,5-tri-
chloro-
phcnol
68
245-246
3.7xlO"8
72.0
2.3,4,6-tetra-
cliioro-
phcnol
69-70
164/23mm
4.2xlO"6
0.10
100.0 .
pentachloro-
phenol
190
309-310
1.2x!0"5
14-19 ppm
Q.OOO S mm
Hg (20'C)
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Except for 2-chlorophenol, which is a liquid, the simple chlo-
rophenols are solids at room temperature and their melting points
increase with chlorine content. The volatility decreases with in-
creasing chlorine content but all of them have pungent, medicinal
odors. All of the simple chlorophenols are easily soluble in common
organic solvents.
The vapor pressure and the concentration of the saturated vapors
of the tri-, tetra-, and pentachlorqphenols are shown in Table II.
These values have been, computed from data in the Chemical Rubber
Handbook (1971).
Commercial Production
The simple .chlorophenols are made by the direct reaction of
chlorine gas with molten phenol. When higher level's of chlorination
are desired, a chloride of iron, aluminum, or antimony is used as a
catalyst. Another mode of preparation is by the hydrolysis of chlo-
rinated benzenes.
Dow Chemical Company and Monsanto Company, together, account for
more than half of the total domestic chlorophenol production. The
largest-volume single product is pentachlorophenol (PCP). Inter-
national Trade Commission production figures for the various chloro-
phenols are shown in Table III. Some of the entries are estimates
based on known volumes of products derived from the chlorophenols.
The production and sale of tetrachlorophenol was discontinued in 1974;
however, this substance is present to the extent of about 12% in
commercial preparations of pentachlorophenol.
The producers of chlorophenols and the major production sites are
shown in Table IV.
Any particular commercial chlorophenol product is likely to be
contaminated with its isomers and material of greater or less chlo-
rination. .Other possible contaminants of greater environmental
concern are a group of extremely toxic chlorinated dibenzodioxins
(Kimbrough, 1972; NIEHS, 1973). A manufacturing process for PCP in
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TABLE II
VAPOR PRESSURES AND CONCENTRATIONS OF THE
SATURATED VAPORS OF TRI-, TETRA- AND PENTACHLOROPHENOL
SUBSTANCE
Pentachlorophenol
Tetrachlorophenol
(2,3,4,6)
Trichlorophenol
(2,4,5)
TEMPERATURE
°C
10
20
30
40
50
10
20
30
40
50
10
20
30
40
50
VAPOR PRESSURE
mm of HQ
1.65 x 10~4
4.67 x 10" 3
1.20 x 10" 3
2.88 x 10" 3
6.60 x 10"
3
1.44 x 10~3
3.72 x 10" 3
8.70 x 10~2
1.95 x 10~2
4.'26 x 10"
2
1.51 x 10~2
3.39 x 10~2
7.20 x 10"!
1.44 x 10"!
2.80 x 10"
SATURATED
VAPOR mq/m3
2.3
6.5
17
40
92
18
45
no
240
520
-
160
350
750
1500
2900 .
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TABLE III
Production of Chlorophenols and Related Products
1 x 106 Ibs. (1 x 109g)
(U.S. Tariff Commission 1960-1971; Doedens, 1964)
I
1960
1961
1962
1963
1964
1965
1966
1967
1968
1969
1970
1971
4-chlorophenoP '
(quinizarin
production)
1.12 (0.518)
1.31 (0.594)
1.43 (0.648)
1.41 (0.640)
—
1.96 (0.889)
2.35 (1.066)
2.07 (0.939)
2.32 (1.052)
2.20 (0.998)
1.61 (0.730)
1.71 (0.776)
(2)
2,4-dichlorophenol v '
(2,4-D + deriv. )
70 (31.75)
80 (36.29)
80 (36.29)
91 (41.26)
108 (48.99)
127 (57.61)
141 (63.95)
161 (73.03)
173 (78.47)
114 (51.71)
81 (36.74)
53 (24.04)
2,4,5-Trichlc
2,4, 5-T and
derivatives
14 (6.35)
15 (6.80)
19 (6.62)
19 (8.62)
24(10.88)
25(11.34)
33(14.99)-
42(19.05)
60(27.22)
18 (8.16)
14 (6.35)
— —
DrophenoP '
phenol and
salts
10 (4.53)
11 (4.99)
12 (5.44)
12 (5.44)
14 (6.35)
13 (5.90)
18 (8.16)
25(11.34)
28(12.70)
—
--
—
2,3,4,6-Tetra
chlorophenol
9 (4.08)
-
'
_
-
-
•-
-
-
-
-
—
Pentachloro-
phenol
39 (17.69)
55 (24.95)
39 ..(17. 69)
34 (15.42)
37 (16.78)
11 ( 4.99)
43 (19.50)
44 (19.96)
49 (22.23)
46 (20.87)
47 (21.32)
51 (23.13)
Footnotes:
1) Estimated from quinizarin production
2) Estimated from 2,4-D production
3) Combined phenol and 2,4,5-T production; 2,4,6-Trichlorophenol production unavailable
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TABLE IV
Chlorophenol Producers and Their
Plant Locations and Capacities
(Chemical Marketing Reporter, 1972;
U.S. Tariff Commission, 1960-1971)
Producer
Capacity
(Compound)*
(1Q6 Ibs.)
Location
Compounds*
Produced by
the Company
Dow Chemical Co.
15.(PCP)
Midland, Mich.
Monsanto Co.
Reichhold Chem., Inc.
Sonford Chem. Co.
Vulcan Materials Co.
26 (PCP)
12 (PCP)
18 (PCP)
(not operating)
7 (PCP)
Sauget, 111.
Tacoma, Wash.
Port Neches, Tex.
Wichita, Kan.
L4-CP, :
"2,4-DCP
2,4,5-TCP
2,4,6-TCP
2,3,4,6-TCP
PCP, and
others.
4-CP," _ I
"2,"4-DCP,~ PCP
PCP
PCP
PCP
Compounds: 4-chlorophenol (4-CP); 2,4-dichlorophenol (2,4-DCP);
2,4,6-trichlorophenol (2,4,6-TCP); 2,4,5-trichlorophenol;
(2,4,5-TCP); 2,3,4,6-tetrachlorophenol (2,3,4,6-TCP);
pentachlorophenol (PCP)..
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which the amount of chlorinated dibenzodioxins are reduced from about
18 ppm hexachloro- and about 1500 ppm octachloro-to 1 ppm and 26 ppm,
respectively, has been announced by one producer (Johnson et al.,
.1973). Other contaminants such as hexachlorobenzene (HCB) are alsc
possible but no discussion of their occurrence was found in the .
literature.
As may be seen in Table III, total production of the simple
chlorophenols now exceeds 100 million pounds per year.
General Patterns of Use
The chlorophenols are used as wood preservatives, fungicides,
herbicides, molluscicides, mold inhibitors and antiseptics. In addi-
tion, members of the class are used as intermediates in the manufac-
ture of other .biocidal materials and of dyes (Doedens, 1964). More
particularly, the major application of 4-chlorophenol is in the
manufacture of dyes and pigments and production estimates' for this
material.are based on the quantities of its derivatives which are
produced (Table 1,11). The major applications of 2,4-dichlorophenol
and 2,4,5-trichlorophenol are in the manufacture of the herbicides
2,4-D and 2,4,5-T. The high levels of production for the latter two
chlorophenols during the last decade reflect the large scale military
applications of herbicides during that period. Pentachlorophenol
(PCP) is used mostly as a wood preservative. PCP is also an effective
herbicide and defoliant. Relatively smaller amounts of trichloro-
phenols and pentachlorophenol are used in paper manufacture, in latex
paints, in adhesives and in cooling tower waters to prevent the growth
of slimes, molds, and bacteria.
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II. ENVIRONMENTAL EXPOSURE FACTORS
Occupational exposures to chlorophenols occur during the manu-
facture, compounding,and application of the substances. Pesticide
applications, accidental spills or the mishandling of effluents can be
the source of environmental contamination. Paper mills and lumber-
treating plants using pentachlorophenol have been particularly noted
as sources (Rudling, 1970). The population can be more generally
exposed as a result of the use and disposal of wood, paint, paper,
crops, and crop residues to which chlorophenols have been applied.
Most lumber millwork manufactured in the U.S. is treated by a 3-minute
immersion in 5% PCP (Winebrenner, 1976).
In addition, chlorophenols can be generated in the environment
when water containing phenol- (a common industrial pollutant) is
chlorinated (Burttschell e_t aj_., 1959). Under the conditions used for
disinfection, the reactions of phenol with chlorine proceed stepwise .
to yield 2- and 4-chlorophenol, 2,6- and 2,4-dichlorophenol and 2,4,6-
trichloropheno]. This is a matter of some practical consequence
because the taste and odor threshholds for the chlorophenols can be
very low. For example, the presence of mono- and dichlorophenols in
water can be perceived at 0.002 ppm. This is in contrast to the
unchlorinated phenol and the trichlorophenols for which the thresh-
holds for taste and odor exceed 1 ppm. When larger amounts of chlo-
rine are added to the water (10 ppm), further reactions occur in which
the phenols are destroyed.
Loos et^ aJL. (1967) have drawn attention to the degradation of the
widely used phenoxyacetate herbicides 2,4-D and 2,4,5-T as sources of
chlorophenols in the environment. In a culture of Arthrobacter, sp.,
and in cell-free extracts from such culture, 2,4-dichlorophenol was
found as an intermediate "metabolite" in the degradation of 2,4-D.
Tetra- and pentachlorophenol may also be formed from the degradation
of hexachlorocyclohexane (Lindane) (Freal et^ al_., 1973). Chlorophenols
have also been noted as products of the metabolism of-chlorinated benzenes
in mammals (Kohli e;t.al_., 1976).
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Some "bioaccumulation" of pentachlorophenol in fish was indicated
by Rudling (1970). From a lake containing 0.003 ppm of PCP, eels were
recovered containing 3 ppm of PCP in their tissue. However, it was
not stated that the eels were caught at the same time or at the same
location at which the water was sampled.
The chlorophenol.s are much more resistant to biodegradation than
the parent compound, phenol. Alexander and Aleem (1961) monitored the
disappearance of a group of phenols from aqueous solutions (50 mg/1)
innoculated with-soil microflora. Their results are shown in Table V.
Several of the compounds survived for more than 72 days. Ingols et^
a!. (1966) performed a similar experiment with acclimated sludge.
Their results, also shown in Table V, indicate that ring degradation
and halide ion producti.on occurred for all of the chlorophenols except
PCP. Later, .Kirsch and Etzel (1973) isolated bacteria capable of
degrading PCP but the.rates of consumption were low and PCP was not
the preferred nutrient.
In field experiments it has been noted that effect of pentachlo-
rophenol is lost several weeks after application. Munkata et al.
(1969) noted that the persistence of PCP activity is enhanced in
shaded.fields. To understand this phenomenon they exposed PCP solu-
tions to sunlight in the laboratory and observed, after ten days,
reductive dechlorination, replacement of chlorine by hydroxyl, forma-
tion of quinones, and the production of .large amounts of resinous
materials. Later, Ide e_t aj_. (1972) incubated PCP solutions with
natural and sterilized soils. They recovered more than 90% of the
•original PCP from the sterilized preparations after 4 weeks and
observed a PCP half life of about 2 weeks in the natural soils. The
degradation products in the latter experiment included chlorophenols
with lesser amounts of chlorine. More recent studies showed that the
concentration of PCP in water, following a spill, declined rapidly in
a few days, but accumulations in the sediments persisted for at least
one 'year (Pierce, 1976). Another recent result is the discovery of
the widespread occurrence of .pentachloroanisole in sewage plant
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TABLE V. COMPILATION OF DATA ON THE
DEGRADATION OF VARIOUS CHLOROPHENOLS
tn
t
Days for ' '
Complete Disappearance
Substance Tested
Phenol
2-chlorophenol
3-chlorophenol •
4-chlorophenol
2,4-dichlorophenol
2,5-dichlorophenol
2,4,5-trichlorophenol
2,4,6-trichlorophenol
2,3,4,6-tetrachlorophenol
pentachlorophenol
Dunkirk
Soil
2
14
72+
9
9
72+
72+
5
72+
72+
Mardin
Soil
1
47
47+
3
5
-
47+
13
- •
-
Degradation in Sludge^ '
Ri ng
Degradation
-
100
100
100 .
100
52'
• -
100
-
0
Halide Ion
Development
_
100
100
100
100
16
-
75
•
0
(1) Alexander and Aleem, 1961
(2) Ingols et a!., 1966
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effluents. The biological methylation of PCP is suspected of being
the source of this material which is much more persistent and has a
higher potential for bioaccumulation than PCP (Kopperman et al.,
1975).
These independent experiments suggest that PCP can be degraded by
several different routes. The most persistent of the degradation
products appears to be the pentachloroanisole. The detailed fate and
effects of that product have not been reported. Tetrachlorohydro -
quinone is cited by Jakobson and Yllner (1971) as a metabolite of PCP
in rats,
Exposure of human populations to at least one member of the
class, pentachlorophenol (PCP), is substantial. Analyses of urine
from 130 agricultural field workers in Hawaii (where PCP was used as
a herbicide) showed PCP concentrations averaging 1.8 ppm and ranging
up to more than 35 ppm. . In a miscellaneous Hawaiian group of 117
people, representative of the general population, the mean concen-
tration found in the urine was 0.04 ppm (Bevenue, Wilson et al.
1967). In a Florida study, the urine of members of the general
population was found to contain 0.002-0.010 ppm PCP (6 individuals)
and .for occupationally exposed persons (3 boatyard workers), values of
from 0.024-0.265 ppm were found (Cranmer and Freal, 1970). Concentra-
tions of PCP in the range 0.002-0.005 ppm were found in an undefined
sample of human adipose tissue presumed to be representative of the
general population (Shafik, 1973). The exposed Hawaiian population'
might be of interest in studies of the long-term effects of the expo-
sure of humans to PCP. More recently traces of PCP have been found in
the urine and semen of university students with no known occupational
exposure. The suspected origins of this material are food packaging
material and lumber used in buildings (Dougherty e_t al_., 1976).
Human exposure can also occur when chlorophenols are present in
drinking water. KaWahara (1971), on the basis of spot monitoring, has
- 16 -
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reported the presence of 2,4-dichlorophenol in the Ohio river at the
intake of the Cincinnati water supply at levels of 0.006 ppm.' Tri-
ch.lorophenol and tetrachlorophenol have also been found in the Cin-
cinnati drinking water; dichlorophenol has been found in the Pitts-
burgh drinking water and pentachlorophenol. has been found in drinking
water at Corvallis, Oregon (EPA, 1975).
- 17 -
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I.II. INCIDENTS OF ENVIRONMENTAL DAMAGE
Human intoxication from exposure to chlorophenols has most often
involved pentachlorophenol in an occupational setting. Examples are
agricultural field applicators and workers in wood-preserving plants
not observing proper handling procedures (instructions regarding
hazard, the use of protective clothing, prompt wash-ups). A total of
30 fatal cases of human PCP poisoning have been reported (Robson et^
al., 1969). Most incidents have been attributed to absorption through
the skin, although respiratory pathways also have been implicated.
Irritation of the eyes, nose, and throat, as well as acne, have been
observed (Kimbroughj, 1972). In humans, the clinical signs of acute
intoxication include profuse sweating, thirst, elevated temperature,
rapid pulse and respiration, and abdominal pain, which can be followed
by death about 24 hours after the first symptoms develop (Bergner,
1965). .
Among the incidents of human intoxication due to pentachloro-
phenol (PCP), nine infants became seriously ill, two fatally, from
contact with diapers laundered with a detergent containing PCP (Robson
e_t aj_., 1969). (This use has since been discontinued.) The children
exhibited fever and sweating described by several observers to be the
most severe they had ever seen and out of proportion to the fever.
Heart rates of 150 per minute, respiratory distress, and enlarged
liver and spleen were observed. The successful therapy consisted of
exchange blood transfusion.
The following case history indicates another kind of toxic
effect on humans. -An adult woman living in a house, in which some of
the interior woodwork.had been treated with PCP became seriously ill
(Mengle, 1976). She lost weight rapidly and complained of weakness
and tightness in her chest. She did not respond to therapy for asthma
and bronchitis. After 3 months she was hospitalized having lost 20
pounds and having become so weak that she could not walk. In the
hospital she recovered her weight and strength. An 'early indication
- 18 -
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of the problem in this case was the death of house plants. Up to 6
ppm of PCP was found in the blood and up to 0.5 ppm PCP.was found in
the urine from this patient. The air in the house was found to
3
contain 0,03 mg/m of PCP. Several similar cases have been reported
by Mengle. ;
Children bathing in water.which had been stored in tanks made of
wood treated with PCP became ill (Chapman and Robson, 1965). One, a
girl age 3-3/4, had high fever, intermittent delirium, and rigors
during the night. Another, a boy age 7, had milder symptoms and the
older members of the family had only mild nasal stuffiness. All
recovered a few days after the exposure ceased and remained well.
Effects ori domestic animals have also been noted: Pigs confined
in farrowing pens made of lumber treated with pentachlorophenol have
died because of this exposure. Two sows showed signs of irritation 5
hours.after confinement and died within 24 hours;.extensive abdominal
burns and necrosis were evident. In another incident, 10 piglets died
one day after birth. The toxic effects were more pronounced in the
younger pigs. These and other incidents of PCP toxicity in animals
have been discussed by Buck e_t aj_. (1973) and by Bevenue and Beckman
(1967).
Another dramatic incident of chlorophenol-related toxicity
involved the death of large numbers of baby chickens which were fed
fats recovered from hides which had been treated with a chlorophenol
preservative. The causative factor was shown to be an extremely toxic
chlorinated dibenzodioxin (chick edema factor) which, either was
present in the original preservative or was generated during the fat
recovery process (Kimbrough, 1972). More recently, 48 horses, hun-
dreds of birds, several cats and dogs, and hundreds of rodents died
. after exposure to the dirt floor in a riding arena after waste .oil had
been applied for dust control. One child also became ill after
exposure in the arena. The oil was said to conta-in residues from the
manufacture of trichlorophenol. More than 300 ppm of tetrachlorodi-
benzodioxin (TCDD) was found in the oil and more than 30 ppm was found
'in the treated dirt (Carter .et_ al_., 1975).
- 19 -
-------
More recently (Rawls et al_., 1976) reported the accidental discharge
of 1000 pounds of trichlorophenol vapor from a chemical plant near
Milan, Italy which killed thousands of wild and domestic animals,
destroyed vegetation, and caused indisposition and major inconvenience
to 5000 local human inhabitants. Particularly high levels of concern
have been expressed because of the known presence of zkg of the very
toxic and teratogenic tetrachlorodibenzodioxin in the discharge.
A "musty taint" in broiler chickens has been observed as a
result of the use of litter made from wood shavings containing penta-
chlorophenol (Patterson, 1972). Analysis showed that this was due to
tetra- and pentachloroanisole formed by the microbial methylation of
the corresponding phenols. More recent work suggests that biomethyl-
ation of chlorinated phenols can occur in sewage treatment plants and
that pentachloroanisole is more persistent and has a much higher
tendency to bioaccumulate in fish than pentachlorophenol itself (Kop-
perman e_t a_l_., 1976).
Kills of fish have occurred in rivers into which pentachloro-
phenol had been accidentally discharged (Papier, 1976; Stark, 1969;
Pierce, 1976).
-20-
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IV. TOXICOLOGY AND BIOLOGY
-------
TABLE VI
LD50's of Various Chlorophenols and Sodium
Chlorophenates After a Single Oral Administration
Phenol
Compound
4-chloro-
2-chloro-
ii ••
2,4-dichloro-
ii
ii
2,4,5-trichloro-
it
n
2,4,5-trichloro-
sodium salt
n
2,3,4,6-Tetrachloro-
Pentachloro-
ii
n
ii
Eentachlpro-
sodium salt
n
n
n
.Animal
rat
blue .fox
mice
rat (male)
rat (female)
mice
rat (male)
rat (female)
rat
rat. (male)
rat (female)
rat
\
rabbit
rat •
rat (male)
rat. (female)
rabbit
n
rat
ti
cuinea pie
W5Q
(mg/kg b
500 ..
440
670
3600
4500
1630
2830
2460 . '
2960
1870
1620
140
70-130*-
27.3-77 .
205 .
135
250-300*
275
•210.6
210
80-160
Reference
Gurova, 1964
Bubnov £t al., 1969
n
Kobayaski e_t_ a^., 1972
Dow Chemical, 1969a
ti
McCollister et_ al. , 1961
Dow Chemical, 1969b
n
Deichman, 1943
Deichmann e_t_ al. , 1942 .
n
Dow Chemical, 1969d
n
Deichmann et al., 1942
Dow Chemical, 1969c
Deichmann et al., 1942
Dow Chemical, 1969c
*Miriimum Lethal Concentration
- 22 -
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clearance half-lives were about three days in monkeys and only one day
in rats. Binding of PCP to plasma protein was noted.
As part of a study of the tumor promoting action of phenol and
related compounds for mouse skin1, Boutwell et^ &]_. (1959) examined the
behavior of 2-chloro-, 3-chloro-, 4-chloro-s 2,4-dichloro-, 2,4,5-
trichloro-, 2,4,6-trichloro-, and pentachlorophenol. When 25 yl of
20% solutions of these compounds in benzene were applied twice weekly
to animals-which had been pretreated with 75 yg of dimethylbenzan-
thracene (DMBA), all but the last two compounds promoted the formation
of papillomas. Their effectiveness as promoters was found to be
comparable to that of phenol itself. Two of the compounds were tested
for carcinogenicity without the prior applications of DMBA and found
to be positive. These were 2-chlorophenol (in dioxane) and 2,4-
dichlorophenol (in benzene). Other compounds in the groups of phenols
tested were negative indicating that the effects were due to the
compound and not the solvent.
Pentachlorophenol is extremely toxic to fish. The median toler-
ance limit (96 hours) for rainbow trout is 0.047 ppm (Matida et al.,
1970). The relative toxicities of the chlorophenols to fish are
somewhat different from that observed for mammals. In the case of the
fish, trichlorophenol is more toxic than monochlorophenol (24-hr TL
is 3.2 mg/1 for 2,4,6-trichlorophenol and 58 mg/1 for 4-chlorophenol)
(Ingolls e_t aj_., 1966).
Phytotoxicity of the chlorophenols also increases with chlorine
content. Blackman e_t al_. (1955) suggest that this effect can be
correlated with the dissociation constants (pK) of the substances.
The toxic effects of the chlorophenols at low dose levels have
been attributed to the inhibition of oxidative phosphorylation. The
efficiency of this process, observed in vitro, increases with increas-
ing degrees of chlorination as shown by Mitsuda e_t aj_. (1963) (Table
VII). The molar concentrations of the various chlorophenols required
to halve the reaction rates are shown. Catalase activity is also
- 23 -
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TABLE VII - COMPILATION OF DATA ON THE
BIOLOGICAL ACTIVITY OF VARIOUS CHLOROPHENOLS
ro
TEST APPLIED
Substances Tested
Phenol
2-chlorophenpl
3-chlorophenol
4-chlorophenol
2,4-dichlorophenol
2,5-dichlorophenol
2,6-»dichlorophenol
2,4,5-trichlorophenol
2,4,6-trichlorophenol
2,3,4,6-tetrachlorophenol
pentachlorophenol
Inhibition of ^
Oxi dative Phos-
phorylation
I50(xlb-6M)
5000
520
150
180
42
-
400
3
18
2
1
i (2'
Inhibition K '
of Catalase
. Activity
I50(xlO-6M)
_
40
200
70
2
20
• -
-
10,000-
-
'
Lemma Minor
(xlO"6M)
_
-
2200
360
-
.
8.4
30
2.6
0.71
50% Growth
Inhibition
Trichoderma
viride (xlO
.
_
'-
-
370 .
53
. -
•
- •
35
3.4
1.2
(3)
for
-6M)
(1) Mitsuda et al (1963), Concentration at which 50% inhibition occurred is tabulated.
(2) Goldacre and Galston (1953), Concentration at which 50% inhibition occurred is tabulated.
(3) Blackman et al (1955)
-------
reduced by chlorophenols as shown in Table VII. Notice, however, that
catalase inhibition .is lower for trichlorophenol than for mono- or
for dichlorophenol.
The practical utility as well as the biological activity of the
various chlorophenols is indicated by the low levels at which they
inhibit the growth of simple plants and microorganisms. The system-
atic increase in effectiveness with increasing chlorine content and,
in particular, the very high effectiveness- of PCP, are shown in Table
VII. .
- 25 -
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V. . ANALYSIS AND MONITORING METHODS
Howard and Durkin (1973) review laboratory methods available for
detecting and assaying the various chlorophenols in air, water, and
biological tissue. These include the use of specific color-forbing
reagents, ultraviolet and infrared absorption, and paper, thin-layer,
and gas chromatography. For trace analyses, a colorimetric procedure
using 4-aminpantipyrene (4-AAP) and gas chromatography with electron
capture have been most widely used. The specialized gas-chromato-
graphic methods for detecting and measuring the occurrence of chloro-
phenols in. liquids and solids (Stark, 1969 and Rudling, 1970) have
been found to be both sensitive and accurate. Dougherty et al.
(1976) has recently applied.a negative-ion mass spectrography tech-
nique which can detect PCP in the picogram range.
The 4-AAP method is considered adequate and is recommended for
the analysis of waste waters for phenols and chlorophenols excepting
tetra- and pentachlorophenol (Am. Pub. Health Assn., 1971). By minor
changes in the test procedure (lowering of the pH and use of a dif-
ferent oxidizing agent), Bencze (1963) found that a 4-AAP method can
be adapted to the assay of the latter two chlorophenols. Bencze's
method appears to be suitable for field analyses but validation of his
procedure has not been found in the literature. Interferences from
other phenolic compounds have'not been ruled out.
The method for the analysis of air for pentachlorophenol endorsed
by the American Conference of Governmental Industrial Hygienists
involves capturing the material on glass fiber or paper'filters
(American Conference of Governmental Industrial Hygienists, 197.1). In
view of the volatility of the substance (section I of this report),
this method does not seem to be appropriate. The use of sintered-
glass bubble tubes containing 1% sodium carbonate solution to collect
the PCP. in air, as recommended by Bencze, overcomes this difficulty.
- 26 -
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VI. REGULATIONS
Both EPA and FDA are aware of potential hazards involved in the
use of chlorophenols and have established criteria for their safe use.
Tri-, tetra-, and pentachlorophenol are registered pesticides. Approved
uses include applications to seeds, fruit trees, textiles (not cloth-
ing), leather., wood, paints, adhesives, pulp and paper, rubber, and
well-drilling muds (EPA, 1974). The registrations on the use of
penta- and trichlorophenol are now being reviewed by the Pesticide
Office of EPA. FDA lists the same chlorophenols, when used at levels
sufficient to prevent deterioration, as acceptable for use in paper
and adhesives which may be'in contact with foods (Code of Federal
Regulations, 1974).
There are EPA Guidelines for the limitation of phenols in indus-
trial effluents. As these are now given (with reference to the use of
an AAP method of analysis) they do not cover tetra- or pentachloro-
phenol, which, because of their greater toxicity and persistence, may
be more hazardous than other common phenols. The hazard potential of
chlorophenols is further recognized in proposed rules for the desig-
nation of hazardous materials (Section 311 of the Federal Water Pollu-
tion Control Act; Federal Register, 1974).
The American Conference of Governmental Industrial Hygienists
•5
(1971) suggests a threshhold limit-value of 0.5 mg/m of pentachloro-
phenol in workroom air. The analytical methods suggested by ACGIH do
not take proper account of the volatility of PCP (note Section I of
this document).
The General Services Administration has a specification for the
procurement of PCP (O-P-1324). This requires at least 83% pentachlo-
rophenol, less than 12% other chlorophenols and less than 5% inert
materials. While the presence of 12% other chlorophenols will not
significantly change the effectiveness of the material as a fungicide,
it does increase the gross volatility of the product." The inerts
would include the dioxiris which have been mentioned above.
- 27 -
-------
There are no controls on the sale or use of products such as wood
or paints which may contain chlorophenol preservatives. The use and
disposition.of such products have been shown to be hazardous. Prepa-
rations containing pentachlorophenol are available in retail stores..
Consumers are not cautioned against applying these to interior wood-
work, to playground equipment, or to furniture where their use can be
hazardous.
- 28 -
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(1969), "Pentachlorophenol Poisoning in a Nursery for Newborn Infants"
I. Clinical Features and Treatment", J. Pediat., 75^, 309-316.
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EPA dated April 2, 1976.
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