vvEPA
United States
Environmental Protection
Agency
Office of Water
Regulations and Standards
Criteria and Standards Division
Washington DC 20460
Ambient
Water Quality
Criteria for
2-chlorophenol
EPA440/SaHB4
October 1980
C-l
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AMBIENT WATER QUALITY CRITERIA FOR
2-CHLOROPHENOl
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
Corvalis, Oregon
Duluth, Minnesota
Gulf Breeze, Florida
Narragansett, Rhode Island
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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.
11
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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
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ACKNOWLEDGEMENTS
Aquatic Life Toxicology:
William A. Brungs, ERL-Narragansett
U.S. Environmental Protection Agency
David J. Hansen, ERL-Gulf Breeze
U.S. Environmental Protection Agency
Mammalian Toxicology and Human Health Effects:
Gary Osweiler (author)
University of Missouri
John F. Risher (doc. mgr.) ECAO-Cin
U.S. Environmental Protection Agency
Jerry F. Stara (doc. mgr.) ECAO-Cin
U.S. Environmental Protection Agency
Rolf Hartung
University of Michigan
Terri Laird, ECAO-Cin
U.S. Environmental Protection Agency
Steven D. Lutkenhoff, ECAO-Cin
U.S. Environmental Protection Agency
Gordon Chesters
University of Wisconsin
Patrick Durkin
Syracuse Research Corporation
Terence M. Grady, ECAO-Cin
U.S. Environmental Protection Agency
Van Kozak
University of Wisconsin
Robert Lingg, HERL
U.S. Environmental Protection Agency
David Ritter, OPP
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, T. Highland, R. Rubinstein.
IV
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TABLE OF CONTENTS
Criteria Summary
Introduction A_j
Aquatic Life Toxicology B_]_
Introduction g_l
Effects g~i
Acute Toxicity g_j_
Chronic Toxicity g_2
Plant Effects B_2
Residues g_2
Miscellaneous g_2
Summary g_3
Criteria g_4
References g_^
Mammalian Toxicology and Human Health Effects C-l
Introduction £_]_
Exposure Q_2
Ingestion from Water Q_2
Ingestion from Food Q_3
Inhalation Q_]_2
Dermal Q_^5
Pharmacokinetics CI15
Absorption Q_^
Distribution r lfi
,. , , . . L-ID
Metabolism ^_-^7
Excretion r 10
Effects ^"Jg
Acute, Subacute, and Chronic Toxicity C-18
Synergism and/or Antagonism Q_22
Teratogenicity and Mutagenicity C-22
Carcinogenicity £_22
Criterion Formulation C-29
Existing Guidelines and Standards C-29
Current Levels of Exposure C_2g
Special Groups at Risk c_30
Basis and Derivation of Criterion r 30
References
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CRITERIA DOCUMENT
2-CHLOROPHENOL
CRITERIA
Aquatic Life
The available data for 2-chlorophenol indicate that acute toxicity to
freshwater aquatic life occurs at concentrations as low as 4,380 yg/1 and
would occur at lower concentrations among species that are more sensitive
than those tested. No definitive data are available concerning the chronic
toxicity of 2-chlorophenol to sensitive freshwater aquatic life but flavor
impairment occurs in one species of fish at concentrations as low as 2,000
wg/1.
No saltwater organisms have been tested with 2-chlorophenol and no
statement can be made concerning acute or chronic toxicity.
Human Health
Sufficient data is not available for 2-chlorophenol to derive a level
which would protect against the potential toxicity of this compound.
Using available organoleptic data, for controlling undesirable taste
and odor qualities of ambient water, the estimated level is 0.1 ug/1. It
should be recognized that organoleptic data as a basis for establishing a
water quality criterion have limitations and have no demonstrated relation-
ship to potential adverse human health effects.
VI
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INTRODUCTION
2-Chlorophenol is a commercially produced chemical used entirely as an
intermediate in the production of other chemicals. It represents a basic
chemical feedstock in the manufacture of higher chlorophenols for such uses
as fungicides, slimicides, bactericides, antiseptics, disinfectants, and
wood and glue preservatives. 2-Chlorophenol is also used to form intermedi-
ates in the production of phenolic resins, and has been utilized in a pro-
cess for extracting sulfur and nitrogen compounds from coal.
2-Chlorophenol (ortho- or o-chlorophenol) is a substituted phenol hav-
ing the empirical formula CgHcOCl. It has a molecular weight of 128.56,
a density of 1.2573 at 25°C, and a vapor pressure of 1 mm Hg at 12.1°C (Sax,
1975; Stecher, 1968). 2-Chlorophenol melts at 8.7°C and exhibits a boiling
point range of 175 to 176°C (Rodd, 1954; Judson and Kilpatrick, 1949).
The spatial configuration and resonance effect of 2-chlorophenol may
suppress the activity of the halogen atom by hydrogen bonding, which partly
accounts for the lower toxicity than the 3- and 4-chlorophenol isomers
(Huang and Gloyna, 1968).
In aqueous solution, 2-chlorophenol is slightly soluble (1,000 mg/1) at
25°C and neutral pH (Henshaw, 1971; U.S. EPA, 1973). The log of the octa-
nol/water partition coefficient for 2-chlorophenol is 2.16 (U.S. EPA, 1978).
2-Chlorophenol is weakly acidic, possesses a pKa of 8.48 in water at 25°C,
and dissociates in alkaline solutions (Judson and Kilpatrick, 1949; Pearce
and Simpkins, 1968). Its monovalent salts, in particular, are soluble in
aqueous solutions, and the degree of solubility is pH-dependent.
Information concerning the presence and fate of 2-chlorophenol is in-
complete or nonexistent. However, the generation of waste sources from the
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commercial production of 2-chlorophenol, its chemically derived products,
and the inadvertent synthesis of 2-chlorophenol due to chlorination of
phenol in effluents and drinking water sources, may clearly indicate its
importance in potential point source and non-point source water contamina-
tion.
The chlorination of phenol from dilute aqueous solutions (Aly, 1968;
Barnhart and Campbell, 1972) and from sewage effluents (Jolley, 1973;
Jolley, et al. 1975) has been demonstrated.
Microbial degradation of 2-chlorophenol under laboratory conditions has
been reported. Studies on the metabolism of the herbicide, 2,4-dichloro-
phenoxyacetic acid (2,4-D), have demonstrated the dechlorination and aro-
matic ring degradation of 2-chlorophenol by an Arthrobacter species (Loos,
et al. 1966). Nachtigall and Butler (1974) reported the complete oxidation
of 2-chlorophenol by Pseudomonas sp. isolated from activated sludge.
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REFERENCES
Aly, O.M. 1968. Separation of phenols in waters by thin-layer chromato-
graphy. Water Res. 2: 587.
Barnhart, E.L. and G.R. Campbell. 1972. The effect of chlorination on
selected organic chemicals. U.S. Government Printing Office, Washington,
D.C.
Henshaw, T.B. 1971. Adsorption/filtration plant cuts phenols from efflu-
ent. Chem. Eng. 78: 47.
Huang, J. and E.F. Gloyna. 1968. Effect of organic compounds on photosyn-
thetic oxygenations. I. Chlorophyll destruction and suppression of photo-
synthetic oxygen production. Water Res. 2: 317.
Jolley, R.L. 1973. Chlorination effects on organic constituents in efflu-
ents from domestic sanitary sewage treatment plants. Ph.D. dissertation.
University of Tennessee.
Jolley, R.L., et al. 1975. Chlorination of cooling water: A source of
environmentally significant chlorine-containing organic compounds. Proc.
4th Natl. Symp. Radioecology. Corvallis, Oregon.
Judson, O.M. and M. Kilpatrick. 1949. The effects of substituents on the
dissociation constants of substituted phenols. I. Experimental measurements
in aqueous solutions. Jour. Am. Chem. Soc. 74: 3110.
A-3
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Loos, M.A., et al. 1966. Formation of 2,4-dichlorophenol and 2,4-dichloro-
phenoxyacetate by Arthrobacter sp. Can. Jour. Microbiol. 13: 691.
Nachtigall, M.H. and R.G. Butler. 1974. Metabolism of phenols and chloro-
phenols by activated sludge microorganisms. Abstr. Annu. Meet. Am. Soc.
Microbiol. 74: 184.
Pearce, P.J. and R.J.J. Simpkins. 1968. Acid strengths of some substituted
picric acids. Can. Jour. Chem. 46: 241.
Rodd, E.H. 1954. Chemistry of Carbon Compounds. III-A. Aromatics. Else-
vier Publishing Co., Amsterdam.
Sax, N.I. 1975. Dangerous Properties of Industrial Materials. 4th ed.
Van Nostrand Reinhold Co., New York.
Stecher, P.G. (ed.) 1968. The Merck Index. 8th ed. Merck and Co., Rah-
way, New Jersey.
U.S. EPA. 1973. Preliminary environmental assessment of chlorinated naph-
thalenes, silicones, fluorocarbons, benzene polycarboxylates, and chloro-
phenols. Syracuse Univ. Res. Corp., Syracuse, New York. U.S. Environ.
Prot. Agency.
U.S. EPA. 1978. In-depth studies on health and environmental impacts of
selected water pollutants. EPA Contract No. 68-010-4646. U.S. Environ.
Prot. Agency, Cincinnati, Ohio.
A-4
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Aquatic Life Toxicology*
INTRODUCTION
Most of the toxicity data available for 2-chlorophenol have been ac-
quired under static testing conditions without chemical measurements. Al-
though this compound is quite soluble in water, one would expect some loss
of the chemical through absorption by the animals and by the testing envir-
onment, which could result in a low estimate of toxicity. Only one chronic
test has been conducted, and since no threshold level was attained, the data
have limited value. Although 2-chlorophenol does not appear to be extremely
toxic to freshwater aquatic life, it has been shown to impair the flavor of
the edible portions of fish at very low concentrations.
No data are available on the effects of 2-chlorophenol on saltwater
aquatic life.
EFFECTS
Acute Toxicity
Ten acute tests have been conducted on four fish and one invertebrate
species (Table 1). Of these, only one was a flow-through test with measured
concentrations. The LCgg values ranged from 2,580 yg/1 for Daphnia magna
(U.S. EPA, 1978) to 20,170 yg/1 for the guppy (Pickering and Henderson,
1966). The species mean acute values (in ug/1) were 4,380 for Daphnia
magna, 8,210 for bluegill, 12,370 for goldfish, 12,400 for the fathead
minnow, and 20,170 for the guppy.
*The reader is referred to the Guidelines for Deriving Water Quality Criter-
ia for the Protection of Aquatic Life and Its Uses in order to better under-
stand the following discussion and recommendation. The following tables
contain the appropriate data that were found in the literature, and at the
bottom of each table are calculations for deriving various measures of tox-
icity as described in the Guidelines.
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The 96-hour LC_n values for chlorinated phenols and bluegills are
directly related to,the degree of chlorination. These values decrease from
6,590 ug/1 for 2-chlorophenol and 3,830 ug/1 for 4-chlorophenol to 60 and 77
ug/1 for pentachlorophenol.
No acute tests have been conducted with 2-chlorophenol and any saltwater
species.
Chronic Toxicity
One chronic test was conducted with the fathead minnow (U.S. EPA, 1978),
but no adverse effects were observed at the highest test concentration of
3,900 ug/1 (Table 2). There are no data available on chronic effects on
freshwater invertebrate species or on any saltwater species.
Species mean acute and chronic values are summarized in Table 3.
Plant Effects
Only one test was conducted with plants (Huang and Gloyna, 1967), and
the effect level (500,000 ug/1) for a freshwater algal species indicates
that plants may not be sensitive to 2-chlorophenol (Table 4).
Residues
A bioconcentration factor was found only for the bluegill (U.S. EPA,
1978). The test was conducted using ^C-2-chlorophenol for 28 days at an
exposure concentration of 9.2 ug/1, and the factor dermined was 214
(Table 5). The depuration rate was rapid with a half-life of less than one
day.
Miscellaneous
As stated in the introduction, 2-chlorophenol was found to impair the
flavor of fishes at lower concentrations than those at which it had a toxic
effect (Henderson, et al. 1960; Shumway and Palensky, 1973) (Table 6). In
the former study, bluegills were exposed for periods of one to four weeks to
S-2
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2,000 ug/1 of 2-chlorophenol and various concentrations of a number of or-
ganic nitriles. A taste panel of twelve members recorded their reaction to
the cooked and coded fish samples. The only chemical that caused a definite
panel reaction was 2-chlorophenol, which reaction ranged from mild to quite
severe nausea. No attempt was made to establish a level of exposure which
would not cause flavor impairment. The other experiment (Shumway and Palen-
sky, 1973), was designed to provide this information. In this study, rain-
bow trout were exposed for 48 hours to a range of concentrations of 2-chlo-
rophenol, and a panel of fifteen judges scored the flavor of the flesh on an
increasing impairment scale of 0 to 6. The results were then plotted
against exposure concentrations and graphically interpreted to arrive at an
estimate of the highest concentration which would not impair the flavor of
the flesh. For 2-chlorophenol, this concentration was estimated to be 60
ug/1 in the exposure water.
The additional toxicity data (Table 6) do not appear to differ dramat-
ically from the data already discussed.
Summary
The LCgQ values for four freshwater fish and one invertebrate species
and 2-chlorophenol range from 2,580 to 20,170 ug/1. The chronic data are of
little value since no threshold level was reached. Flesh-tainting data in-
dicate that the edible portions of fishes may become tainted at water con-
centrations as low as 2,000 ug/1. No data are available for any saltwater
species and 2-chlorophenol.
B-3
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CRITERIA
The available data for 2-chlorophenol indicate that acute toxicity to
freshwater aauatic life occurs at concentrations as low as 4,380 yg/1 and
would occur at lower concentrations among species that are more sensitive
than those tested. No definitive data are available concerning the chronic
toxicity of 2-chlorophenol to sensitive freshwater aauatic life but flavor
impairment occurs in one species of fish at concentrations as low as 2,000
ug/1.
No saltwater organisms have been tested with 2-chlorophenol and no
statement can be made concerning acute or chronic toxicity.
B-4
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Table 1. Acute values for 2-chlorophenol
CO
I
CTI
LC50/EC50
Species Method* (|ig/l)
Species Mean
Acute Value
(ug/l) Reference
FRESHWATER SPECIES
Cladoceran, S, U 7,430
Daphnla magna
Cladoceran, S, U 2,580
Daphnla magna
Goldfish, S, U 12,370
Carasslus auratus
Fathead minnow S, U 11,630
Plmephales promelas
Fathead minnow S, U 14,480
Plmephales promelas
Fathead minnow, FT, M 12,400
Plmephales promelas
Guppy S, U 20,170
Poec ilia r et 1 cu 1 ata
Bluegill, S, U 6,590
Lepomis macrochirus
Bluegill, S, U 10,000
Lepomis macrochirus
Bluegill (juvenile), S, U 8,400
Lepomis macrochirus
Kopperman, et at.
1974
4,380 U.S. EPA, 1978
12,370 Pickering &
Henderson, 1966
Pickering i
Henderson, 1966
Pickering &
Henderson, 1966
12,400 Phipps, et at.
Manuscript
20,170 Pickering &
Henderson, 1966.
U.S. EPA, 1978
Pickering i
Henderson, 1966
8,210 Henderson, et al.
1960
* S = static, FT = flow-through, U = unmeasured, M = measured
No Final Acute Value is calculable since the minimum data requirements are not met.
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00
I
CTl
Table 2. Chronic values for 2-chlorophenoI (U.S. EPA, 1978)
Species Mean
Limits Chronic Value
Species Method* pig/I) (ug/l)
FRESHWATER SPECIES
Fathead minnow, E-L >3,900
Plmephales promelas
* E-L = embryo-IarvaI
No acute-chronic ratio is calculable.
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Table 3. Species mean acute and chronic values for 2-chlorophenol
I
-J
Number
5
4
3
2
1
Spec 1 es
Guppy,
Poecllla reticulata
Fathead minnow,
Plmephales promelas
Goldfish,
Carassius auratus
Bluegll 1 (juvenl le)
Lepomls macrochirus
Cladoceran,
Daphnla inagna
Species Mean Species Mean
Acute Value* Chronic Value
(ug/l) (ug/l)
FRESHWATER SPECIES
20,170
12,400
12,370
8,210
4,380
Acute-Chronic
Ratio"
-
* Rank from high concentration to low concentration by species mean acute value.
**See the Guidelines for derivation of this ratio.
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Table 4. Plant values for 2-chlorophenol (Huang & Gloyna, 1967)
Result
Effect (ug/l)
FRESHWATER SPECIES
I
oo
Alga, Reduction 500,000
Chlorella pyrenoldosa in chlorophyll
In 72 hrs
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Table 5. Residues for 2-chlorophenoI (U.S. EPA, 1978)
BioconcentratIon Duration
Tissue Factor (days)
FRESHWATER SPECIES
Bluegill, Whole body 214 28
Lepomls macrochlrus
03
I
>£>
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Table 6. Other data for 2-chlorophenol
03
I
Species
Rainbow trout,
Salmo gairdnerl
Goldfish,
Carassfus auratus
Goldfish,
Carasslus auratus
Fathead minnow,
Plmephales prone las
Bluegl 1 1,
Lepomls macrochlrus
Bluegl 1 1 ( juvenl le),
Lepomls macrochlrus
Duration
48 hrs
8 hrs
24 hrs
192 hrs
1 wk
48 hrs
Effect
FRESHWATER SPECIES
ETC*
42? mortality
LC50
LC50
F 1 a vor I mpa 1 rment
LC50
Result
(ug/l)
60
31,100
16,000
6,340
2,000
8,100
Reference
Shumway & Palensky,
1973
Gersdorff & Smith,
1940
Kobayashl, et al.
1979
Phlpps, et al.
Manuscript
Henderson, et al.
1960
Lammerlng & Bur bank,
1960
*ETC = the highest estimated concentration of material that will not impair the flavor of
flesh of exposed fish.
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REFERENCES
Gersdorff, W.A. and L.'E. Smith. 1940. Effect of introduction of the halo-
gens into the phenol molecule on toxicity to goldfish. I. Monochlorophe-
nols. Am. Jour. Pharmacol. 112: 197.
Henderson, C., et al. 1960. The effect of some organic cyanides (nitriles)
on fish. Proc. 15th Ind. Waste Conf., Purdue Univ., Eng. Bull. Ed. 45: 120.
Huang, J. and E. Gloyna. 1967. Effects of toxic organics of photosynthetic
reoxygenation. Environ. Health Engin. Res. Lab. PB 216-729.
Kobayashi, «., et al. 1979. Relation between toxicity and accumulation of
various chlorophenols in goldfish. Bull. Japan Soc. Sci. Fish. 45: 173.
Kopperman, H.L., et al. 1974. Aaueous chloronation and ozonation studies.
I. Structure-toxicity correlations of phenolic compounds to Daphnia magna.
Chem. Biol. Inter. 9: 245.
Lammering, M.W. and N.C. Burbank. 1960. The toxicity of phenol, o-chloro-
phenol and o-nitrophenol to bluegill sunfish. Engin. Bull., Purdue Univ.
Engin. Ext. Serv. 106: 541.
Phipps, G.L., et al. The acute toxicity of phenol and substituted phenols
to the fathead minnow. (Manuscript)
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Pickering, Q.H. and C. Henderson. 1966. Acute toxicity of some important
petrochemicals to fish. Jour. Water Pollut. Control Fed. 38: 1419.
Shumway, D.L. and J.R. Palensky. 1973. Impairment of the flavor of fish by
water pollutants. U.S. Environ. Prot. Agency, EPA-R3-73-010, U.S. Govern-
ment Printing Office, Washington, D.C.
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.
B-12
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Mammalian Toxicology and Human Health Effects
INTRODUCTION
The potential for exposure of man to any synthetic chemical exists
through any of several modes. These modes include: 1) exposure of indus-
trial workers during synthesis, formulation, packaging, or transport; 2) ex-
posure of users of the product at either a commercial or retail level;
3) contact with residues or metabolites of the product as a result of using
commodities or environments containing the material; and 4) contact with the
chemical as a metabolite of some other product.
To understand the route of entry of a chemical, one must first examine
the sources and properties of the material. 2-Chlorophenol is a commercial-
ly produced chemical used as an intermediate in the production of other
chemicals, and represents a basic chemical feedstock for the manufacture of
higher chlorophenols.
Direct chlorination of phenol leads to the formation of both 2- and
4-chlorophenols. These isomers can be separated by fractional distillation,
since the difference in their boiling points is greater than 40°C. Most of
the commercially used 2-chlorophenol in the U.S. is recovered as a byproduct
of the manufacture of 4-chlorophenol by direct chlorination of phenol.
The chlorination of phenol in aqueous solutions to form 2-chlorophenol
and higher phenols has been demonstrated under conditions similar to those
used for the disinfection of wastewater effluents and may represent a source
of contamination (Aly, 1968; Barnhart and Campbell, 1972). Since chlorine
and phenol do not normally occur in stoichiometric amounts, the concentra-
tions of 2-chlorophenol actually produced in FLO are likely to be lower
than those found in experimental studies (Barnhart and Campbell, 1972).
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Higher levels of chlorination become increasingly less favored. 2-Chloro-
phenol has been synthesized from phenol and chlorine at concentrations as
low as 10 and 20 mg/1, respectively, within one hour (Barnhart and Campbell,
1972). Other studies have demonstrated the formation of 2-chlorophenol (1.7
ug/1) and numerous other chlorinated compounds during the chlorination of
sewage effluents and power plant cooling waters (Jolley, 1973; Jolley, et
al. 1975).
EXPOSURE
Ingestion from Water
2-Chlorophenol may exist in the aquatic environment in the dissolved
form, associated with suspended matter and bottom sediments, and absorbed in
biological tissues. Metal salts of this compound have greater water solu-
bility, and if introduced or formed j£ situ would exist primarily in the
dissolved form. Chlorophenols, being weak acids tend to ionize, depending
upon the pH of the system. They are almost completely nonionized in aqueous
solutions with a pH lower than 5, and become increasingly dissociated as the
pH rises (Cserjesi, 1972).
No information could be found on the amounts of 2-chlorophenol present
in finished water intended for human consumption.
In one study, industrial waste discharge was the principal point source
of water pollution. During the manufacture of chlorophenols and 2,4-D,
there is chemical waste generated as the result of incomplete reaction of
the starting reactants, by-product formation, and incomplete recovery of
desired products. Thus, the wastes contain a mixture of chlorophenols and
other compounds. Waste arising from the manufacture of phenoxyalkanoic her-
bicides showed amounts of 2-chlorophenol ranging from a trace to 6 percent
(Sidwell, 1971) (Tables 1 and 2) of the total phenols and chlorophenols.
C-2
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TABLE 1
Chlorophenols in Industrial Plant Waste*
0
1
oo
Date
Temp. °C
PH
Chlorophenols (mg/1)
Phenoxy Acids (mg/1)
Total Solids (mg/1)
25 January
12
7.5
68
167
6,960
3 March
18
7.6
118
183
40,100
21 April
21
7.4
125
241
76,320
28 May
28.5
7.4
112
235
104,860
27 August
24
7.0
74
199
11,000
*Source: Sidwell, 1971
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TABLE 2
Relative Chlorophenol Content of Industrial Waste*
Date
Phenol Type
2-chloro
phenol
2,6-DCP
2,5-DCP
2,4-DCP
2,4,6-TCP
4-chloro
2,4,5-trichloro
25 January
2.9
3.4
9.9
trace
73.6
2.8
2.5
4.7
3 March 21 April 28 May
Percent of Total Phenols Present
6.1
6.2
41.7
6.2
17.9
9.9
12.1
trace
trace
1.7
38.8
1.7
20.0
19.5
18.3
trace
trace
24.8
30.5
trace
11.4
13.3
20.0
trace
27 August
trace
trace
3.0
1.8
89.0
3.4
2.8
trace
*Source: Si dwell, 1971
-------
Other possible point sources are chemical spills and the washing of
containers or drums in which chlorophenols or the herbicide 2,4-dichloro-
phenoxyacetic acid (2,4-D) are stored.
Contamination of water with 2-chlorophenol may occur by (1) chlorina-
tion of phenol present in natural water and primary and secondary effluents
of waste treatment plants (Burttschell, et al. 1959; Eisenhauer, 1964; Barn-
hart and Campbell, 1972), (2) direct addition of the chemicals or as contam-
inants or degradation products of 2,4-0 used for aquatic weed control, and
(3) wet and dry atmospheric fallout.
No direct data were found to show actual measured concentrations of
2-chlorophenol in water courses, impoundments, wells, or other human water
supply sources.
Based on the relatively limited sources of water contamination by
2-chlorophenol, as well as the demonstrated decomposition in many aquatic
situations, water should be a minor route of ingestion of 2-chlorophenol.
2-Chlorophenol may be removed from water by several mechanisms. One
study (Ettinger and Ruchhoft, 1950) indicates that the dissipation of
2-chlorophenol is largely microbiological. Persistence appears to be short,
but limnological factors, such as oxygen deficiency, may delay degradation
(Aly and Faust, 1964). Microorganisms found in activated sludge and waste
lagoons have been demonstrated to degrade 2-chlorophenol rather readily
(Sidwell, 1971; Nachtigall and Butler, 1974).
Ettinger and Ruchhoft (1950) found that low concentrations (1 mg/1) of
2-chlorophenol added to a usual dilution of domestic sewage were not removed
during periods of 20 to 30 days, presumably due to the absence of microorga-
nisms capable of attacking the chemical. When a similar concentration was
added to polluted river waters, the compound dissipated in 15 to 23 days.
C-5
-------
Addition of a seed, consisting of water from a previous persistence experi-
ment, increased significantly the removal of 2-chlorophenol. Apparently,
the seed introduced some organisms already adapted to the chemical. This
study also indicated that the removal of monochlorophenols requires the
presence of an adapted microflora.
Ingols, et al. (1966) obtained data indicating the dechlorination of
2-chlorophenol and other monochlorophenols within three days of exposure to
an activated sludge system (Table 3).
Primary treatment consists essentially of settling solids, after
screening off large materials. Settling may not remove 2-chlorophenol from
water, since it is adsorbed poorly on particulate or suspended matter.
Secondary treatment involves the removal of organic matter from waste
water by biological processes. Since 2-chlorophenol and 2,4-dichlorophenol
(2,4-DCP) are known to be easily biodegradable, secondary treatment should
provide excellent removal of these chemicals.
Baird, et al. (1974), employing Warburg respiratory techniques, demon-
strated that biodegradation of 2-chlorophenol at 1 mg/1 in activated sludge
was complete within three hours. Increasing the concentration to 100 mg/1
considerably reduced the rate of respiration such that only 20 percent was
degraded in six hours. This is probably due to microbial toxicity from
2-chlorophenol at this concentration. In a sludge not acclimated with high
levels of 2-chlorophenol, certain amounts of the compound may be degraded
initially, while oxidative intermediates that appear subsequently could be
toxic to the microbial population. This indicates that 2-chlorophenol may
persist longer, due to direct or indirect toxic effects, if waste containing
high levels of the chemical is discharged into an unacclimated body of water.
C-6
-------
TABLE 3
Degradation of Chlorophenols in Acclimated, Activated Sludgea>')
o
Compound
2-chlorophenol
3-chlorophenol
4-chlorophenol
2,4-DCP
2,5-DCP
2,4,6-TCP
NaPCP
Dichloroquinone
2,5-DCP benzoquinone
Amount of
of
%
100
100
100
100
52
100
0
100
30
ring degradation
compound
days
3
2
3
5
4
3
4
1
1
Development
%
100
100
100
100
16
75
0
50
0
of Chloride Ion
days
4
3
3
5
4
3
4
3
1
aSource: Modified from Ingols, et al. 1966
bConcentration of 100 mg/1
-------
While a number of studies indicate rapid dissipation of 2-chlorophenol
from waters by several mechanisms, human exposure cannot be fully evaluated
unless studies are conducted measuring the 2-chlorophenol content in waters
receiving wastes from point sources of chlorophenols or their precursors.
Evidence of such studies was not found.
Ingestion from Food
Contamination of human foods with 2-chlorophenol could occur via soil,
plants, animals, or aquatic sources. In all cases, any contamination is
probably indirect and primarily a result of the use and subsequent metabo-
lism of phenoxyalkanoic herbicides.
In 1971, U.S. farmers applied almost 16,000,000 kg of 2,4-0, represent-
ing 15 percent of all organic herbicide usage [U.S. Department of Agricul-
ture (USDA), 1974].
Although 2-chlorophenol appears to be short-lived in soils, the data
are inconclusive, and factors affecting its persistence need further study.
However, microbial degradation is the apparent major route of dissipation
for chlorophenols in soils. For 2,4-OCP, which is more likely to reach the
soil system as a contaminant and degradation product of 2,4-D, its degrada-
tion under field conditions could be faster than degradation of the herbi-
cide itself. The role of microorganisms in the degradation of 2,4-D has
been conclusively demonstrated (Loos, 1975), and under favorable conditions
2,4-D disappears from soils in about 30 days (Kearney, et al. 1969). Warm,
moist, well-aerated soils with ample organic matter content promote the pro-
liferation of microorganisms known to metabolize 2,4-D. One of the chemi-
cals in the metabolic pathway may be 2-chlorophenol. Limited information
indicates the biodegradability of 2-chlorophenol (Walker, 1954; Baird, et
al. 1974). Several genera of bacteria isolated from soil are capable of
C-8
-------
metabolizing 2-chlorophenol. Pseudomonas sp., Nocardia sp., Mycobacterium
coeliacum, and Bacillus sp. were demonstrated to oxidize 2-chlorophenol to
3-chlorocatechol (Spokes and Walker, 1974). The fate of the catechol inter-
mediate was elucidated in a study by Evans, et al. (1971) of the metabolism
of 2,4-0 by Pseudomonas sp. Using 2,4-D as sole carbon source for Pseudo-
monas strains isolated from soil, the herbicide was metabolized to 2,4-OCP,
2-chlorophenol, 3,5-dichlorocatechol, and a-chloromuconate, which was fur-
ther metabolized to release Cl" and unidentified metabolites. The appear-
ance in culture of 2-chlorophenol suggests the nonoxidative elimination of
chlorine from 2,4-OCP or, possibly, 2,4-0 itself. The accumulation of
m-chloromuconate is probably a further manifestation of this phenomenon,
since it is likely formed by enzymatic cleavage of 3-chlorocatechol, derived
from either 2-chlorophenol or 3,5-dichlorocatechol.
It is probable that the sorption behavior of 2-chlorophenol is similar
to 2,4-0. In natural soil systems, sorption may not be extensive, thereby
favoring downward movement in soil with water.
The persistence of 2-chlorophenol in soils was studied by Walker (1954)
using the percolation technique. Solutions of 2-chlorophenol (1.0 g/4 1 tap
water) were allowed to percolate through 100 g of a Rothamsted soil (light
clay with a pH of 6.8), and the disappearance of the initial and subsequent
doses was measured. Two-thirds of the initial dose disappeared in 10 days.
Disappearance of subsequent doses occurred approximately twice as rapidly as
that of the first dose, suggesting microbial participation. Further evi-
dence of microbial decomposition was indicated by the more rapid disappear-
ance of 2-chlorophenol in fresh than in sterilized soil within seven days of
percolation.
C-9
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Furthermore, the participation of soil microorganisms in the dissipa-
tion of 2-chlorophenol and other chlorophenols was reported by Alexander and
Aleem (1961) using suspensions of two silt loam soils. Metabolism of the
chemicals was evidenced by more rapid disappearance of incremental additions
of the compounds than initial enrichments. Also, inhibition of degradation
occurred on addition of sodium azide, a toxic agent. 2-Chlorophenol disap-
peared rapidly in suspensions of Dunkirk and Mardin silt loams; disappear-
ance was faster for the latter soil.
No information was found on the uptake, absorption, and translocation
of 2-chlorophenol by plants. The movement of 2-chlorophenol can only be
inferred from the few available studies of 2,4-DCP in plants and from the
potential for 2-chlorophenol to occur as a metabolic intermediate in the
degradation of 2,4-0.
The metabolism of 2-chlorophenol in vascular plants is not well stud-
ied. The only available report demonstrated that 2-chlorophenol may be in-
activated by glycoside formation in plant tissue. It has been demonstrated
that when certain nonnaturally occurring chemicals are absorbed by various
plants, glycoside formation takes place with the foreign chemical serving as
the aglycon. Miller (1941) demonstrated that the metabolic fate of 2-chlo-
rophenol in tomato plants included glycoside formation. s-o->chlorophenyl -
gentiobioside (a glycoside of 2-chlorophenol) was isolated from the roots of
these tomato plants. No evidence for the formation of this glycoside in
shoots was found. The fate of this metabolic product of 2-chlorophenol in
plants is not known and warrants further investigation.
Domestic animals, including poultry, could ingest feeds containing pes-
ticides or drink water contaminated directly with 2-chlorophenol and
2,4-DCP. Although some studies indicate the appearance and distribution of
C-10
-------
fn)
2,4-OCP in tissues of animals fed with 2,4-0 and Nemacide0' [0-(2,4-dichlo-
rophenol)-0,0-diethylphosphorothioate] (Clark, et al. 1975; Sherman, et al.
1972), in none of the studies was there evidence cited to indicate residues
of 2-chlorophenol. Furthermore, Bjerke, et al. (1972) reported no contami-
nation of milk and cream from cows given a 2,4-0 (100 to 1,000 mg/kg) diet.
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 BCF for a lipid-soluble compound in the tissues of various
aquatic animals seems to be proportional 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
percent 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 consumption 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 lipids for consumed freshwater and estuarine fish and shellfish
is 3.0.
A measured steady-state bioconcentration factor of 214 was obtained for
2-chlorophenol, using bluegills containing about 1 percent lipids (U.S. EPA,
1978). An adjustment factor of 3.0/4.8 = 0.625 can be used to adjust the
measured BCF from the 3.0 percent lipids of the bluegill to the 2.3 percent
lipids that is the weighted average for consumed fish and shellfish. Thus,
C-ll
-------
the weighted average bioconcentration factor for 2-chlorophenol and the edi-
ble portion of all freshwater and estuarine aquatic organisms consumed by
Americans is calculated to be 214 x 0.625 = 134.
Inhalation
The dispersal and distribution of 2-chlorophenol in air has apparently
not been studied. One potential source of environmental pollution by
2-chlorophenol, however, is the manufacture of 2,4-D herbicides. Secondly,
since 2-chlorophenol is volatile (1 mm Hg at 12°C), any 2-chlorophenol gen-
erated as a decomposition product of applied 2,4-0 could be subject to gen-
eral environmental dispersal. A third possibility for inhalation exposure
could be the burning of containers, trash, or plant material contaminated
with 2-chlorophenol. No data addressing the monitoring of air or workplace
environments for 2-chlorophenol have been found. Therefore, the potential
sources for human exposure through inhalation remain speculative.
Because of the volatility of 2-chlorophenol and the processes employed
in its manufacture, the most probable source of inhalation exposure to
2-chlorophenol would occur in manufacturing plants producing 2-chlorophenol
or possibly 2,4-0. The separation of 2-chlorophenol from 2,4-dichlorophenol
involves fractional distillation which, if not done with regard to worker
safety, could result in exposure by inhalation. The potential for airborne
exposure to 2-chlorophenol in the general environment as a result of point
source pollution has not been reported.
Although inhalation exposure to 2-chlorophenol associated with related
products in general use (e.g., 2,4-D herbicide) does not seem likely, no
data to verify atmospheric 2-chlorophenol presence or absence under such
conditions have been found. Potential for such exposure seems quite low for
several reasons. First, the principal general environmental source of
C-12
-------
2-chlorophenol would be 2,4-D or its decomposition products. Since there is
little evidence of 2-chlorophenol occurring as a permanent soil or plant
metabolite of 2,4-D, the amount available to be volatilized would be either
limited or absent. Secondly, any 2-chlorophenol which might be formed in
soil or water is rapidly degraded by microorganisms (see Ingestion section),
while 2-chlorophenol in plants is inactivated as a glycoside (Miller, 1941).
A third potential route of exposure, the burning of chlorophenol-con-
taining products, has not been studied. Incineration of phenoxy herbicides
should be accompanied by investigations of potential formation and/or dis-
persal of 2-chlorophenol, as well as other chlorophenols.
Direct studies of potential or actual exposure to 2-chlorophenol have
not been found. However, after considering the nature of the production,
uses, and persistence of 2-chlorophenol, inhalation exposure of the general
population does not seem a significant threat, except for specific occupa-
tional settings in cases of large accidental spills. A recent case involv-
ing potential exposure of the general population to 2-chlorophenol is in-
cluded here for reference purposes.
On January 11, 1979, a chemical spill occurred at Sturgeon, Missouri,
as a result of a train derailment. Ortho-chlorophenol and phenol were major
components of the spilled material. As a result, U.S. Environmental Protec-
tion Agency personnel were asked to supervise the clean-up of the spill.
C-13
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Values of ortho-chlorophenol determined by the U.S. EPA (Fairless, 1979) at
several dates after the spill are as follows:
Date of Collection 2-Chlorophenol Concentration
1979 in Air (ppm)
January 11 0.013
January 11 0.004
January 11 0.190
January 29 <0.0005
January 29 <0.0005
January 29 <0.0005
March 6 <0.0003
March 6 <0.0003
March 6 <0.0003
March 6 0.0029
Analyses for 2-chlorophenol were made from the urine of several individuals
working or residing in Sturgeon, Missouri, within several months after the
spill. Results of those analyses conducted for the American Public Health
Association (1979) are as follows:
1. Four adult males assisting in clean-up operations at the spill
site had a mean 2-chlorophenol urine concentration of 1.98 ppm
(range 1.4 - 2.6) on March 7, 1979. By April 11, 1979, when these
same four individuals were again sampled, all had no detectable
amount of 2-chlorophenol in their urine, (detection limit 0.25
ppm).
2. Nine persons residing in Sturgeon, Missouri within 40 to 200 feet
of the spill site all had no detectable amount of 2-chlorophenol
in their urine when sampled on April 11, 1979. These nine persons
had no history of direct contact with 2-chlorophenol at the spill
site and did not assist in clean-up operations. The only obvious
source of exposure to 2-chlorophenol would have been via inhala-
tion of chlorophenol from the atmosphere in Sturgeon.
It should be noted that even though extremely low levels of
2-chlorophenol were measured by the U.S. EPA, a noticeable odor of
chlorophenols could be detected for several months after the
spill. Thus, organoleptic detection of chlorophenols is possible,
even when measurable levels in air or urine cannot be found.
C-14
-------
Dermal
2-Chlorophenol dermal absorption data have not been found. Since the
compound is lipid soluble and likely to be poorly ionized at an environment-
al pH (Farquharson, et al. 1958), it could be readily absorbed through in-
tact skin. Dermal absorption and resultant body burdon merit study.
As indicated for inhalation exposure, the only potentially significant
dermal exposure to 2-chlorophenol would occur in the manufacture of handling
of 2-chlorophenol or products which contain it. Ordinary and accepted meth-
ods of skin protection would be expected to prevent dermanl exposure to
2-chlorophenol. Dermal exposure to 2-chlorophenol from other sources (soil
water, plant metabolites of 2,4-D) is considered to be insignificant for the
same reasons as stated in the section on inhalation.
PHARMACOKINETICS
Absorption
Direct data on the absorption of 2-chlorophenol by man or experimental
animals have not been found. Chlorophenol compounds are generally consid-
ered readily absorbed, as would be expected from their high lipid solubility
and low degree of ionization at physiological pH (Doedens, 1963; Farquhar-
son, et al. 1958). Although skin irritation and dermal absorption are re-
ported as characteristic of monochlorophenols, direct quantitative data con-
cerning the irritant potential of 2-chlorophenol have not been found. Tox-
icity studies to be discussed later indicate that 2-chlorophenol can be ab-
sorbed and can result in toxicosis; however, quantitative data for 2-chloro-
phenol absorption by various routes have not been found.
2-Chlorophenol may occur in mammals as a metabolite of other compounds.
Exposure of rabbits to chlorobenzene has resulted in the formation of
2-chlorophenol (Lindsay-Smith, et al. 1972).
C-15
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In addition, Selander, et al. (1975) reported the conversion of chloro-
benzene to a mixture of monochlorophenols in perfused rat liver. Apparent-
ly, three different enzyme systems catalyze the conversion of chlorobenzene
to 2-, 3-, and 4-chlorophenols.
Investigation of 2,4-D metabolism in mammals (Clark, et al. 1975) has
not indicated 2-chlorophenol to be a metabolite of such exposure, while
2,4-OCP is considered the major metabolite.
Distribution
Direct information about the distribution and transportation of 2-chlo-
rophenol is not available. However, at least two reports (Spencer and Wil-
liams, 1950; von Oettingen, 1949) on the rabbit and dog, respectively, indi-
cate urinary excretion of 2-chlorophenol. Furthermore, since metabolites of
2-chlorophenols are identified as glucuronide and sulfate conjugates, it is
possible that the liver might contain proportionally large amounts of
2-chlorophenol. Two reports concerning lesions induced by 2-chlorophenol
(Patty, 1963; Bubnov, et al. 1969) indicate changes in liver and kidney,
thus visually confirming the renal and hepatic distribution. No information
concerning hepatic excretion or any indication of an enterohepatic cycle was
found. While compounds of high lipophilia (which would include 2-chloro-
phenol) are often considered to accumulate in adipose tissue, no information
to this effect was found for 2-chlorophenol. In fact, related compounds
(2,4-dichlorophenol and pentachlorophenol) are considered to have relatively
short half-lives (Clark, et al. 1975; Osweiler, et al. 1977). Whether this
is true for 2-chlorophenol remains to be established. Since animals dosed
with 2-chlorophenol display convulsive activity within several minutes of
exposure (Farquharson, et al. 1958; Angel and Rogers, 1972), it can be as-
sumed that the compound traverses the blood brain barrier and is distributed
C-16
-------
in part in the central nervous system. The concentrations of 2-chlorophenol
in brain and other organs or tissues during toxicosis remain to be deter-
mined.
Metabolism
The metabolism of 2-chlorophenol in man is not known. n experimental
animals, von Oettingen (1949) cites work by Karpow (1893) showing that dogs
excreted 87 percent of administered 2-chlorophenol as conjugates with sul-
fate and glucuronic acid. The rabbit also apparently conjugates 2-chloro-
phenol derived from chlorobenzene exposure (Lindsay-Smith, et al. 1972) by
formation of sulfate and glucuronide conjugates. However, 2-chlorophenol
was reported as only a minor metabolite of chlorobenzene in the rabbit
(Lindsay-Smith, et al. 1972). Furthermore, only a small portion of the
chlorophenols formed were monochlorophenols, and less than 6 percent of the
free and metabolized chlorophenols was the 2-chlorophenol isomer.
Selander, et al. (1975) demonstrated that chlorobenzene is converted to
o-, m-, and p-chlorophenols in perfused rat livers, as well as by noncellu-
lar systems including microsomes, post mitochondrial supernatant, and recon-
stituted soluble hemoprotein-monooxygenase systems. Pretreatment with the
inducing agents 3-methylcholanthrene and phenobarbital increased the forma-
tion of chlorophenols, while carbon monoxide and SKF 525A^ (e-diethyl-
aminoethyl diphenylpropylacetate) inhibited formation of o-, m-, and p-chlo-
rophenols. The approximate j_n vivo ratios for formation of o-, m-, and
p-chlorophenol were 1:2:4, respectively. Thus, formation of 2-chlorophenol
via metabolism of chlorobenzene does not appear to be a significant or major
route of exposure. While it is possible that 2-chlorophenol could form in
man or animals as a result of exposure to phenoxyacetic acid herbicides,
there are no data to support this conjecture. In fact, Clark, et al.
C-17
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(1975), in studies of the metabolism of phenoxy herbicides, reported the
major metabolite to be 2,4-OCP and did not mention detection of 2-chloro-
phenol.
Based on experimental work in two species (dogs and rabbits), it ap-
pears that mammalian metabolism of 2-chlorophenol follows the expected route
for phenol metabolism (i.e., formation of conjugates of glucuronides and
sulfates, with detection of these metabolites primarily in the urine).
Excretion
Studies of the excretion route or rate for 2-chlorophenol in man were
not found. As mentioned before, von Oettingen (1949) reviewed the data of
Karpow (1893), in which dogs given 2-chlorophenol excreted 87 percent of the
compound in urine as sulfate and glucuronide conjugates. However, data were
not developed from which the rate of excretion or half-life could be calcu-
lated. Lindsay-Smith, et al. (1972) identified phenolic metabolites in rab-
bit urine after administration of chlorobenzene. Of the free and conjugated
forms of chlorophenols in rabbit urine, less than 6 percent was present as
2-chlorophenol.
No data have been found concerning measurement of tissue residues of
2-chlorophenol, either from direct administration or by formation as a
metabolite of other compounds, nor have sufficient data accumulated to allow
calculation of a half-life for 2-chlorophenol.
EFFECTS
Acute, Subacute, and Chronic Toxicity
The acute toxicity of 2-chlorophenol has been studied in a variety of
organisms. The compound is considered to be an uncoupler of oxidative phos-
phorylation (Mitsuda, et al. 1963) and a convulsant poison (Farquharson, et
al. 1958; Angel and Rogers, 1972). No reports of the subacute or chronic
C-18
-------
toxicity of 2-chlorophenol have been found. This represents a serious data
gap in the toxicologic evaluation of 2-chlorophenol.
Mammalian toxicity of 2-chlorophenol has not been well studied. There
are no reports of human or domestic animal toxicoses from accidental or
intentional exposure to 2-chlorophenol. Furthermore, there is no evidence
linking 2-chlorophenol exposure in industrial workers to the chloracne, an
effect often associated with higher chlorophenols (Huff and Wassom, 1974),
nor is there evidence to suggest that the toxic dioxins are contaminants of,
or are formed from, 2-chlorophenol.
Doedens (1963) briefly characterized the toxicity of 2-chlorophenol as
being "likely" to be corrosive and irritating to the eyes and skin. How-
ever, specific data on the effects of 2-chlorophenol were not presented.
The data from relatively few acute toxicological studies in laboratory ani-
mals are the only ones from which an evaluation of 2-chlorophenol can be
made (Table 4). It may be seen by inspection of Table 4 that the subcutane-
ous minimum lethal dose (MLD) of 2-chlorophenol in the rabbit (950 mg/kg) is
approximately 8 times that of the intravenous MLD, implying that the subcu-
taneous route retards bioavailability of 2-chlorophenol. At a physiological
pH of 7.4, however, 2-chlorophenol is approximately only 5 percent ionized
(Farquharson, et al. 1958); such a low degree of ionization would not ac-
count for this lessening of toxicity by the subcutaneous route.
The LD5Q data in Table 4 indicate that 2-chlorophenol is more toxic
by the oral than the subcutaneous route. At relatively acidic pH (e.g.,
stomach), the pKa of 2-chlorophenol (8.65) would allow for a highly union-
ized state, which is conducive to ready absorption from the stomach or the
less acidic upper intestine. This effect could explain the greater oral
toxicity of 2-chlorophenol.
C-19
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TABLE 4
Lethal Doses of 2-Chlorophenol for Experimental Animals
Animal
Rat
Rat
Albino rat
Rabbit
i
INJ
0
Rabbit
Mouse
Guinea pig
Blue fox
Unknown mammal
Route of Administration
Oral
Subcutaneous
Intraperitoneal
Subcutaneous
Intravenous
Oral
Subcutaneous
Oral
Oral
LD50
(mg/kg)
670
950
2303
950
1203
670
8003
440
440
Source
Deichmann, 1943
Deichmann, 1943
Farquharson, et al .
1958
Christensen and
Luginbyhl, 1975
Kuroda, 1926,
cited in
von Oettingen,
1949
Bubnov, et al . 1969
Christensen and
Luginbyhl, 1975
Bubnov, et al . 1969
Christensen and
Luginbyhl, 1975
aMLD (minimum lethal dose) values
-------
Among the various species tested by the same route, there is a surpris-
ing similarity among acute toxicities. This would imply that initial ab-
sorption, metabolism, detoxification, and affected organs are quite similar
among various species. It would be expected then that chronic toxicity
would vary according to ability of a species to metabolize, inactivate, and
excrete 2-chlorophenol on a long term basis. Unfortunately, studies of long
term or chronic effects have not been reported.
Signs of 2-chlorophenol intoxication in rats are similar, whether the
compound is administered subcutaneously, intraperitoneally, or orally. The
toxicological picture includes restlessness and increased rate of respira-
tion within a few miniutes following administration. Somewhat later, motor
weakness develops, and tremors and convulsions induced by noise or touch
occur. Eventually, dyspnea and the appearance of coma result and continue
until death (Farquharson, et al. 1958). Following fatal poisoning, lesions
in the rat include marked kidney injury, red blood cell casts in the tub-
ules, fatty infiltration of the liver, and hemorrhages in the intestine
(Patty, 1963). Bubnov, et al. (1969) report a similar pathological picture
in the blue fox and the mouse. At lethal concentrations, 2-chlorophenol
caused fatty degeneration of the liver, renal granular dystrophy, and necro-
sis of the stomach and intestinal mucosa. These signs are very similar to
acute phenol toxicosis (Patty, 1963).
The convulsive action of 2-chlorophenol in mice was studied by Angel
and Rogers (1972). Following intraperitoneal administration of 2-chloro-
phenol, a rapid onset of convulsions was noted. A simple exponential decay
of the convulsive effect was noted, which the authors speculated could have
been a result of removal from the central nervous system (CNS) by a simple
chemical reaction. However, no information directly addressing this point
is available.
C-21
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Farquharson, et al, (1958) state that as phenol is progressively chlo-
rinated, the molar toxicity shows a tendency to increase when pK value falls
below 7. Furthermore, convulsions are. the most characteristic effect of
chlorophenols with pK values of 8.65 or higher. Thus, it may be that con-
vulsions are in some way associated with undissociated molecules. No stud-
ies were found which attempted to evaluate the passage of chlorophenols with
different pK values across the blood-brain barrier.
Synergism and/or Antagonism
Reports of studies directly assessing the synergism or antagonism of
2-chlorophenol by other compounds were not found. Since 2-chlorophenol is a
weak uncoupler of oxidative phosphorylation (Mitsuda, et al. 1963), it may
be expected that concomitant exposure to other uncouplers (e.g. pentachloro-
phenol, dinitrophenol) would enhance that effect. In addition, exposure to
chlorinated hydrocarbon insecticides, with their characteristic convulsant
activity, might also produce a magnified response.
Any agent causing liver damage sufficient to decrease the conjugation
of 2-chlorophenol with glucuronide or sulfate could conceivably alter the
excretion and/or toxicity of the parent compound. However, there are no
specific studies to reflect such an effect, it is only speculative that the
general tendency of conjugation to render a compound less toxic and more
amenable to excretion would also operate in the case of 2-chlorophenol.
Teratogenicity and Mutagenicity
Pertinent data could not be located in the available literature con-
cerning the teratogenicity and mutagenicity of 2-chlorophenol.
Carcinogenicity
The report of Boutwell and Bosch (1959) is the only one found dealing
with the tumorigenicity of 2-chlorophenol, Repeated application of phenol
C-22
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and some substituted phenols has been reported to promote skin tumors in
mice after a single initiating dose of dimethylbenzanthracene (DMBA). Pap-
illomas have developed in mice treated with phenol alone (not exposed to
DMBA). In the studies of Boutwell and Bosch (1959), two trials included
evaluation of 2-chlorophenol. In one of these, 25 \i1 of a 20 percent solu-
tion of 2-chlorophenol was applied twice weekly to female Sutter mice two to
three months of age for 15 weeks. This application followed an initiating
dose of 0.3 percent DMBA in benzene. Tumorigenic response was measured as
fo11ows:
(1) The percentage of surviving mice bearing one or more papillo-
mas was ascertained.
(2) The total number of papillomas on all surviving mice was
counted and divided by the number of^urvivors to give the
average number of papillomas per mouse.
(3) The number of mice bearing malignant tumors was determined.
Results of the promoter trial with 2-chlorophenol are presented in
Table 5. Related promoter experiments with phenol, as well as the benzene
control, are included for comparative purposes. Based on the data, the
authors concluded that the promoting activity of 2-chlorophenol is similar
to that of phenol.
In a second experiment, Boutwell and Bosch (1959) administered in a
similar manner 20 percent 2-chlorophenol in dioxane, but for 12 weeks and
without an initiator. Results of this trial are also included in Table 5.
In both trials, 2-chlorophenol was associated with a high incidence of pap-
illomas. When DMBA was used as an initiator, 10 percent of the survivors
developed carcinoma at the skin site of application; however when 2-chloro-
phenol alone was used, no carcinogenic response was observed.
Since the study was designed primarily to detect promoting activity,
the effect of 2-chlorophenol as a primary carcinogen is not well defined.
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TABLE 5
Appearance of Skin Tumors in Mice Treated Cutaneously with Phenols following a
Cutaneous Dose of 0.3X Dimethylbenzanthracene (DMBA) in Acetone a
Treatments'*
Benzene control
10% phenol in
benzene. No DMBA.
^itX phenol in
acetone.
20% phenol in
benzene.
20% 2-chlorophenol
in benzene.
20% ?-chlorophenol
in dioxane. No DMBA.
Time Animals
Examine
(weeks)
12
20
12
24
15
12
No. of mice
(survivors/total )
12/12
24/30
21/24
10/33
31/35
28/30
Survivors
with Papillomas
0
33
56
100
61
46
Average
Papillomas
per Survivor
0
0.62
_
3.20
1.48
0.64
Survivors with
Epithelial Carcinomas
*
0
1 t
5
20
10
0
aSource: Modified from Boutwell and Bosch, 1959
^All received DMBA except where stated
-------
The study uses dermal applications of a phenolic compound at 20 percent con-
centration in organic solvents. The concentration is high enough that hair
follicles and sebaceous glands are destroyed, and the papillomatous response
observed may have developed in response to chemical and/or physical damage
from application of an irritant compound. Even with this harsh treatment,
no malignant neoplasia were observed, except when DMBA had been used as an
initiator. The only neoplasia observed were at the site of the direct ap-
plication. This study does not evaluate systemic carcinogenesis, and the
route of administration is not appropriate to the prescribed models for car-
cinogenic risk assessment. The route of administration (dermal) has no
established relationship to oral exposure.
Odor and taste thresholds for 2-chlorophenol in water have been report-
ed by a number of investigators. Hoak (1957) reported the odor threshold of
phenol and 19 phenolic compounds. In this study conducted at the Mellon In-
stitute in Pittsburgh, Pennsylvania, a panel of two or four persons sniffed
samples of pure phenolic compounds in odor-free water, which had been heated
to 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 per-
sons, and the flask with the lowest perceptible odor was noted by each indi-
vidual sniffer. The lowest concentration detected was considered to be the
threshold of the chemicals tested; chlorinated phenols were the compounds
most easily detected. The odor thresholds reported for 2-chlorophenol were
0.33 ug/1 at 30°C and 2.5 wg/l at 60°C (Hoak, 1957). Hoak speculated that
odor should be expected to become more noticeable as temperature increases;
however, in evaluating a series of chlorophenols and cresols, it was found
that some compounds had higher odor thresholds at 30°C, while others were
higher at 60°C.
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Burttschell, et al (1959) made dilutions of 2-chlorophenol in carbon-
filtered tap water and used a panel of from four to six persons to evaluate
odor and taste. Tests were carried out at room temperature, which the in-
vestigator estimated to be 25°C. If a panel member's response was doubtful,
the sample was considered negative. The geometric mean (2 u9/l for odor and
yg/1 for taste) of the panel responses was used as the organoleptic
thresholds. Since the data presented did not indicate a range of responses,
it is very possible that the odor threshold for some people in the Burtt-
schell group was near the 0.33 ug/1 value of Hoak.
Campbell, et al. (1958) studied the taste thresholds of six odor-pro-
ducing chemicals. Solutions of the chemicals were prepared using redis-
tilled water. Panels of 21 or 22 experienced judges participated in differ-
ent organoleptic tests of the triangle type. Concentrations of chemicals
chosen for the triangle tests were such that the odd sample would be identi-
fied by more than 35, but less than 100 percent of the judges. Samples were
served in 25 ml portions, and the judges were asked only to identify odd
sample. When 50 percent of the judges correctly separated the samples in a
given triangle test, the concentration of 2-chlorophenol used in that test
was considered to be the threshold level. Although a number of judges were
able to detect the presence of 2-chlorophenol at a concentration of 2 yg/1,
a threshold level of 6 yg/1 was reported based on the experimental methodol-
ogy used. It is interesting to note that, in this same study, a concentra-
tion of 1 ug 2-chlorophenol/I was determined to be the threshold for impair-
ment of coffee brew, while eight of the tasters noted some impairment at
0.5 wg/l.
Dietz and Traud (1978) used a panel composed of 9 to 12 persons of both
sexes and various age groups to test the organoleptic detection thresholds
C-26
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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 approximately five minutes, and sniffed at room tempera-
ture (20 to 22°C). For each test, water without the phenolic additive was
used as a background sample. The odor tests took place in several individ-
ual rooms in which phenols and other substances with intense odors had not
been used previously. Geometric mean values were used to determine thresh-
old levels. To determine taste threshold concentrations of selected phenol-
ic compounds, a panel of four test individuals tasted water samples contain-
ing various amounts of phenolic additives. As a point of comparison, water
without phenolic additives was tasted first. Samples with increasing phe-
nolic concentrations 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 0.1 ug/1 for taste and 10
ug/1 for odor for 2-chlorophenol.
None of the four organoleptic studies described above, however, indi-
cated whether the determined threshold levels made the water undesirable or
unfit for consumption.
Studies on the impairment of fish flavor by 2-chlorophenol have also
been reported. Henderson, et al. (1960) found that a concentration of 2,000
ug/1 caused impaired flavor of bluegill sunfish after a 28-day static, re-
newal exposure. Only one concentration was tested, so no dose-related
threshold was determined. Shumway and Palensky (1973) found 60 ug/1 to be
an estimated threshold concentration during a 48-hour flow-through exposure
of rainbow trout. Schulze (1961) determined that 15 ug/1 affected the fla-
vor of carp after a 3-day flow-through exposure. Boetius (1954) studied the
C-27
-------
flavor impairment of eels and oysters (species unspecified) in static sys-
tems, and found flavor impairment in brackish water at a concentration of
0.125 ug/l after 11 days for eels and four days for oysters. Methodology
for determining flavor impairment was particularly lacking in the Boetius
paper. Because of the subjectivity of flavor impairment, test methodology
(especially in the selection of, and evaluation by, the test panel) is par-
ticularly important in the critical evaluation of a flavor impairment study.
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CRITERION FORMULATION
Existing Guidelines and Standards
As can be determined from the available literature, no standards or
guidelines exist for 2-chlorophenol.
Current Levels of Exposure
Overall, exposure of the general population to 2-chlorophenol would
most likely occur in the form of consumption of phenol-containing chlorinat-
ed drinking water. This would limit exposure primarily to water supplies
contaminated by a point source of 2-chlorophenol. Such sources should be
relatively easy to identify and monitor, since analytical techniques for
detection of 2-chlorophenol are available. Apparently, such monitoring is
not being done.
Since 2-chlorophenol is not a universally reported metabolite of 2,4-D,
exposure of the general population through use of 2,4-0 is only speculative.
If small amounts of 2-chlorophenol are formed and gain access to ground
water or the soil, they are not expected to persist, in view of 2-chlorophe-
nol 's ready susceptibility to microbial attack.
Inhalation or dermal exposure have not been identified as significant
routes of exposure for the general population. Since 2-chlorophenol is not
used directly for any broad environmental application, it is logical to ex-
pect little exposure for the general population. However, due to lack of
atmospheric monitoring data, any estimates of potential exposure are purely
speculative. There have been no reported investigations of the persistence,
movement, and fate of 2-chlorophenol in the atmosphere (U.S. EPA, 1979).
For industrial workers manufacturing or handling 2-chlorophenol, inha-
lation exposure should be considered a possible hazard, since the compound
is volatile. Dermal exposure could also occur, since both phenol and cer-
C-29
-------
tain chlorophenols are known to be dermally absorbed. However, specific
absorption studies for 2-chlorophenol were not found (Doedens, 1963). Ac-
cording to a recent review by the U.S. Environmental Protection Agency, "No
data on the routes or rates of entry of 2-chlorophenol in humans were found"
(U.S. EPA, 1979).
Due to the lack of monitoring data or human body burden values, the
extent of human exposure cannot be determined.
Special Groups at Risk
The only special group expected to be at risk of high exposure to
2-chlorophenol is industrial workers involved in the manufacture or handling
of 2-chlorophenol. No data were found to relate exposure or body burden to
conditions of contact with 2-chlorophenol.
Basis and Derivation of Criterion
Insufficient data exist to indicate that 2-chlorophenol is a carcino-
genic agent. The only study performed (Boutwell and Bosch, 1959) was de-
signed to detect the promoting activity of 2-chlorophenol with dimethylbenz-
anthracene-initiated tumors. (Under certain environmental conditions,
2-chlorophenol may produce a small amount of dibenzo-p-dioxins.) The recent
National Cancer Institute (NCI, 1978) bioassay report of possible carcinoge-
nicity of dibenzo-p-dioxin has concluded that it was not carcinogenic for
Osborne-Mendel rats or B6C3F1 mice. Due to the absence of sufficient tox-
icological data on which to base a criterion, the ambient water quality cri-
terion for 2-chlorophenol is based on organoleptic data. As substantive and
reliable human and other mammalian toxicity data become available, a crite-
rion level based upon health effects may be postulated.
The data from Hoak (1957), Burttschell, et al. (1959), and Oietz and
Traud (1978) all indicated that low microgram concentrations of 2-chlorophe-
C-30
-------
no! in water are capable of producing a discernible odor. Burttschell, et
al. (1959), Campbell, et al. (1958), and Oietz and fraud (1978) further ob-
served a distinct flavor alteration of water at low microgram or sub-micro-
gram levels of this chemical. The Burttschell, et al. (1959) and Dietz and
Traud (1978) odor studies did not indicate a range of responses; however,
because of the variability inherent in such procedures, it is certainly pos-
sible that the odor threshold for some evaluators (at least in the Burtt-
schell, et al. group) would extend downward toward the 0.33 ug/1 value of
Hoak. Similarly, Burttschell, et al. (1959) did not indicate a range of
concentrations in their taste test, and Campbell, et al. (1958) did not test
concentrations of 2-chlorophenol below 2 u9/l; so it is also possible that
some of the tasters in these tests could have at least been capable of de-
tecting, if not actually detecting in the case of the Burttschell, et al.
group, concentrations of 2-chlorophenol down near the 0.1 ug/1 taste thresh-
old determined by Dietz and Traud (1978). Thus, the data from these four
studies are considered to be reasonably mutually supportive (i.e., Hoak's
0.33 pg/1 for odor; Burttschell, et al. group's geometric mean values of 2
ug/1 for odor and 4 ug/1 for taste; Campbell, et al.'s derived 6 ug/1
threshold for taste; and Dietz and Traud's geometric mean values of 10 ug/1
for odor and 0.1 ug/1 for taste).
The taste threshold determined by Oietz and Traud (1978) for the detec-
tion of 2-chlorophenol in water is used as the basis for the ambient water
quality criterion. The Dietz and Traud study was chosen for a number of
reasons. These authors present a recent study involving well-defined proce-
dures and a number of documented controls. This study utilized "fresh"
water from the base outlet of the Verse Dam (Germany) for all experiments.
The water was described as clear and neutral with respect to both odor and
C-31
-------
taste. These conditions are considered to more closely approximate the con-
ditions of ambient water found in lakes, rivers, and streams than would
those of the Hoak (1957), Burttschell, et al. (1959), or Campbell, et al.
(1958) studies, which utilized carbon-filtered laboratory distilled or re-
distilled water. The 20 to 22°C temperature of the water in the Dietz and
Traud odor and taste tests might also more closely approximate the tempera-
ture at which water is normally consumed than do the 30*C or 25°C tempera-
tures used in the studies of Hoak (1957) and Burttschell, et al. (1959),
respectively [Campbell, et al. (1958) did not indicate the temperature of
the water used in their study]. However, it is recognized that the tempera-
ture of water consumed by humans is quite obviously variable, and no study
will represent the temperature of water consumed by all Americans.
Therefore, based on the prevention of undesirable organoleptic charac-
teristics, the criterion level for 2-chlorophenol in water is 0.1 ug/1. It
should be emphasized that this criterion is based on aesthetics rather than
health effects.
C-32
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ft V S. GOVERNMENT PRINTING OFFICE • 19BO 720-016/4359
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