2-CHLOROPHENOL
Ambient Water Quality Criteria
Criteria and Standards Division
Office of Water Planning and Standards
U.S. Environmental Protection Agency
Washington, D.C.

-------
U22145
CRITERIA DOCUMENT
2-CHLOROPHENOL
CRITERIA
Aquatic Life
[For 2-chlorophenol the criterion to protect freshwater
aquatic life]as derived using the guidelines^is 60 pq/1
as a 24-hour average and^the concentration^should not exceed
180 jug/lj at any time.
^For saltwater aquatic life, no criterion for 2-chloro-
phenol can be derived using the Guidelines], and there are
insufficient data to estimate a criterion using other proce-
dures.
Human Health
[For the prevention of adverse effects due to the organo-
leptic properties of 2-chlorophenol in water, the criterion
is 0.3 /jg/lTj

-------
2-CHLOROPHENOL
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 for
the manufacture of higher chlorophenols for such uses as
fungicides, slimicides, bactericides, antiseptics, disinfec-
tants, and wood arid glue preservatives. 2-Chlorophenol
is also used to form intermediates in the production of
phenolic resins and has been utilized in a process for ex-
tracting sulfur and nitrogen compounds from coal.
2-Chlorophenol (ortho- oro-chlorophenol) is a substi-
tuted phenol having the empirical formula CgH^Cl. It has
a molecular weight of 128.56, a density of 1.2573 at 25
degrees, and a vapor pressure of 1 mm Hg at 12.1 degrees
C (Sax, 1975; Stecher, 1968). 2-Chlorophenol melts at 8.7
degrees C and exhibits a boiling point range of 175-176
degrees C (Rodd, 1954; Judson and Kilpatrick, 1949).
The spatial configuration and resonance effect of 2-
chlorophenol may suppress the activity of the halogen atom
via hydrogen bonding and partly account for the lower toxi-
city as compared to the 3- and 4-chlorophenol isomers (Haung
and Gloyna, 1968).
In aqueous solution, 2-chlorophenol is slightly soluble
(1,000 mg/1) at 25 degrees C and neutral pH (Henshaw, 1971;
U.S. EOA, 1973). The log of the octanol/water partition
coefficient for 2-chlorophenol is 2.16 (U.S. EPA, 1978).
It is weakly acidic, possesses a pKa of 8.48 in water at
A-l

-------
25 degrees C, and will dissociate in alkaline solutions
(Judson and Kilpatrick, 1949; Pearce and Simpkins, 1968).
The monovalent salts particularly are soluble in aqueous
solutions and the degree of solubility is pH dependent.
Information concerning the presence and fate of 2-chloro-
phenol is incomplete or nonexistent. However, the generation
of waste sources from the commercial production of 2-chloro-
phenol, 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 contamination.
The chlorination of phenol from dilute aqueous solutions
(Aly, 1968; Barnhart and Campbell, 1972) and from sewage
effluents (Jolly, 1973; Jolly, et al. 1975) have been demon-
strated. However, no data regarding 2-chlorophenol concen-
trations in finished drinking water are available.
Microbial degradation of 2-chlorophenol under laboratory
conditions has been reported. Studies on the metabolism
of the herbicide, 2, 4-dichlorophenoxyacetate (2, 4-D),
have demonstrated the dechlorination and aromatic ring degrada-
tion 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. Although these laboratory
studies suggested microbial oxidation as an important degrada-
tion route for 2-chlorophenol, sufficient data are not avail-
able to reach conclusions regarding the persistence of this
compound in the environment.
A-2

-------
Several studies have reported an odor threshold concen-
tration of 2-chlorophenol in aqueous solutions. Other studies
have demonstrated the property of 2-chlorophenol to produce
undesirable taint in freshwater vertebrate species. Some
work has further demonstrated that phenolic flavor can be
acquired by fish flesh through contaminated fish food or
by other animals eating contaminated fish.
Although 2-chlorophenol has been reported to be less
toxic than the higher chlorophenols, its low odor threshold
in water and its tainting properties are considered a poten-
tial threat to certain beneficial uses of water and the
utilization of aquatic life as a food source.
A-3

-------
REFERENCES
Aly, O.M. 1968. Separation of phenols in waters by thin-
layer chromatography. 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 effluent. Chem. Eng. 78: 47.
Huang, J., and E.F. Gloyna. 1968. Effect of organic com-
pounds on photosynthetic oxygenations. I. Chlorophyll de-
struction and suppression of photosynthetic oxygen produc-
tion. Water Res. 2s 317-366.
Jolly, R.L. 1973. Chlorination effects on organic consti-
tuents in effluents from domestic sanitary sewage treatment
plants. Ph.D. dissertation. University of Tennessee.
Jolly, R.L., et al. 1975. Chlorination of cooling water:
A source of environmentally significant chlorine-containing
organic compounds. Proc. 4th Natl. Symp. Radioecology.
Corvallis, Ore.

-------
Judson, D.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.
Loos, M.A., et al. 1966. Formation of 2, 4-dichlorophenol
and 2, 4-dichlorophenoxyacetate by Arthrobacter Sp. Can.
Jour. Microbiol. 13: 691.
Nachtigall, M.H., and R.G. Butler. 1974. Metabolism of
phenols and chlorophenols 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. Elsevier 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 Merk Index. 8th ed. Merck
and Co., Rahway, N.J.
U.S. EPA. 1973. Preliminary environmental assessment of
chlorinated naphthalenes, silicones, fluorocarbons, benzene
polycarboxylates, and chlorophenols. Syracuse Univ. Res.
Corp., Syracuse, N.Y. U.S. Environ. Prot.jAgency.
A-5

-------
U.S. EPA. 1978. In-depth studies on health and environ-
mental impacts of selected water pollutants. EPA Contract
No. 68-010-4646. U.S. Environ. Prot. Agency, Washington,
D.C.
A-6

-------
AQUATIC LIFE TOXICOLOGY*
FRESHWATER ORGANISMS
Introduction
Most of the toxicity data available for 2-chlorophenol
has been acquired under static testing conditions without
chemical measurements. Although this compound is quite
soluble in water, one would expect some loss of the chemical
through absorption by the animals and by the testing environ-
ment. This would result in a low estimate of the toxicity
and thus require adjustment by use of the Guideline adjustment
factors. The one flow-through test that was found does
not provide sufficient data to suggest a deviation from
the Guidelines. Only one chronic test has been run, and
since no threshold level was attained, the data have limited .
value.
Although 2-chlorophenol does not appear to be extremely
toxic to aquatic life, it has been shown to impair the flavor
of the edible portions of fish at very low concentrations.
This fact will therefore be used in deriving the criterion.
Acute Toxicity
Eleven acute tests were run, representing four species
of fish (Table 1) and one invertebrate species (Table 2).
~The reader is referred to the Guidelines for Deriving Water
Quality Criteria for the Protection of Aquatic Life C43
FR 21506 (May 18, 1978) and 43 FR 29028 (July 5, 1978)3
and the Methodology Document in order to better understand
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 the calcu-
lations for deriving various measures to toxicity as described
in the Guidelines.
B-l

-------
0 these tests, only one was flow-through with measured
concentrations. The adjusted LC50 values ranged from 2,185
yu/1 for Daphnia magna (U.S. EPA, 1978) to 12,380 /ig/1 for
fathead minnow (Phipps, et al. Manuscript). By species,
the average adjusted concentration was 4,239 jug/1 for Daphnia
magna, 4,312 jig/1 for bluegill, 6,763 yug/1 for goldfish,
8,885 /ig/1 for fathead minnow, and 11,027 jug/1 for guppy.
For the limited information available, the range of species
sensitivities appears to be relatively narrow.
Application of the Guideline adjustment and sensitivity
factors to the fish acute tests results in a concentration
of 1,800 yug/1. Since this concentration is lower than that
for the flow-through test, it becomes the Final Fish Acute
Value. The Final Invertebrate Acute Value is 180 /ig/1,
which becomes the Final Acute Value since it is lower than
the Final Fish Acute Value.
The 96-hour LC50 values for chlorinated phenols and
bluegills (U.S. EPA, 1978) are directly related to the degree
of chlorination. These values decrease from 6,590 /jg/1
for 2-chlorophenol and 3,830 /jg/1 for 4-chlorophenol to
60 and 77 yug/1 for pentachlorophenol. These data and those
for intermediate chlorinated phenols can be correlated with
the n-octanol/water partition coefficient with a correlation
coefficient of 0.95. Data for other species do not correlate
as well.
B-2

-------
Chronic Toxicity
One fish chronic test was found (U.S. EPA, 1978), but
no adverse effects were observed at the highest test concen-
tration (3,900 jug/1). After adjustment for species sensitiv-
ity, the Final Fish Chronic Value is greater than 290 jig/1.
There are no data available for chronic toxicity to inverte-
brate species.
Plant Effects
Only one test was conducted with plants (Huang and
Gloyna, 1967), and the effect level (500,000 jug/1) indicates
that plants may not be sensitive to 2-chlorophenol (Table
4).
Residues
A bioconcentration factor was found only for the bluegill
14
(U.S. EPA, 1978). The test was run using C-2-chlorophenol
for 28 days at an exposure concentration of 9.2 jig/1, and
the factor determined was 214 (Table 5). The depuration
rate was rapid with a half-life of less than one day. Since
no maximum permissible tissue level exists for this compound,
no Residue Limited Toxicant Concentration can be calculated.
Miscellaneous
As stated in the introduction, 2-chlorophenol was found
to impair the flavor of fish at lower concentrations than
those at which it had a toxic effect (Henderson, et al.
1960 and Shumway and Palensky, 1973) (Table 6). In the
former study, bluegills were exposed for periods of one
to four weeks to 2,000 /ig/1 of 2-chlorophenol and various
concentrations of a number of organic nitriles. A taste
B-3

-------
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 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 Palensky,
1973), however, was designed to provide this information.
In this study, rainbow trout were exposed for 48 hours to
a range of concentrations of 2-chlorophenol, 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 jig/1 in the exposure
water, and since this value is the lowest of all the data
discussed, it becomes the Final Chronic Value.
B-4

-------
CRITERION FORMULATION
Freshwater - Aquatic Life
Summary of Available Data
The concentrations below have been rounded to two signi-
ficant figures.
Final Fish Acute Value = 1,800 pg/1
Final Invertebrate Acute Value = 180 ^ig/1
Final Acute Value = 180 pg/1
Final Fish Chronic Value = greater than 290 jug/1
Final Invertebrate Chronic Value = not available
Final Plant Value = 500,000 jug/1
Residue Limited Toxicant Concentration = not available
Final Chronic Value = 60 /ig/1 for tainting of fish flesh
0.44 x Final Acute Value = 79 jig/1
The maximum concentration of 2-chlorophenol is the
Final Acute Value of 180 /ig/1 and the 24-hour average concen-
tration is the Final Chronic Value of 60 pg/1. No important
adverse effects on freshwater aquatic organisms have been
reported to be caused by concentrations lower than the 24-
hour average concentration.
CRITERION: For 2-chlorophenol the criterion to protect
freshwater aquatic life as derived using the guidelines
is 60 pg/1 as a 24-hour average and the concentration should
not exceed 180 jug/1 at any time.
B-5

-------
Table 1. Freshwater fish acute values for 2-chlorophenol
Staaniaa
Bioaaaay Teat	Tine	LC50
HfithPfl* ponfft** iMll lUSLllL
Adjusted
LC&O
Hetar^n^
Goldfish,	S	U
Caraastua auratua
Fathead minnow,	S	U
Pimephalea promelas
Fathead minnow,	S	U
Pimephalea promelas
Fathead minnow,	FT	M
Pimephalea promelas
Guppy,	S	U
Poeciila reticulatua
Bluegill,	S	U
Lepomla macrochirus
Bluegill (Juvenile),	R	U
Lepomla macrochirus
Bluegill,	S	U
Lepomla macrochirua
Bluegill (juvenile),	S	U
Lepomla macrochirus
96
96
96
96
96
96
48
96
96
12,370 6,763 Pickering & Henderson,
1966
11,630 6,358 Pickering & Henderson,
1966
14,480 7,916 Pickering & Henderson,
1966
12,380 12,380 Phippa, et al. Manuscript
20,170 11,027 Pickering & Henderaon,
1966
6,590
3,603 U.S. EPA, 1978
8,100 3,587 Lammerlng & Burbank, 1960
10,000 5,467 Pickering & Henderson,
1966
8,400 4,592 Henderson, et al. 1960
* S  static, FT - flow-through, R  renewal
** H  measured, U  unmeasured
7 211
Geometric mean of adjusted values  7,211 ug/l  ^ ^ " 1,800 ug/1
Loweat value from a flow-through teat with measured concentrations " 12,380 yg/1

-------
Table 2. Freshwater Invertebrate acute values	for 2-chlorophenol
Adjusted
Bioassay Test Tina L50	LCbO
Organism Hetiiou* cor>c .** IntB.t tui/A>	
-------
03
i
CO
Table 3, Freshwater fish chronic values for 2-chlorophenol (U.S. EPA, 1978)
Chronic
Limits Value
Organism	feat	lug/11 lug/l>
Fathead minnow,	E-L	>3,900 >1,950
Pimephales promelaa
* E-L - embryo-larval
Geometric mean of cl
Lowest chronic value - >1,950 |ig/l
Geometric mean of chronic values - >1,950 pg/1 *"^7^ " >290 |tg/l

-------
Table 4. Freshwater plant effects for 2-chlorophenol (Huang & Gloyna, 1967)
organism
Missi
Concentration
Alga,
Chlorella
pyrenoldoaa
Reduction
In chlorophyll
In 72 hrs
500.000

-------
Table 5. Freshwater residues for 2-chlorophanoL (U.S. EPA, 1978)
. . 08,
Organism	Blocancantration factoi
Bluegill,	214	28
Lepomia macrochlrua
a
l-
O

-------
Table 6. Other freshwater data for 2-chlorophenol
Organlam
Teat
emtisn Ettsct
Result
Bststsuss
Rainbow trout,
Salmo nalrdnerl
Goldfish,
Carasslus auratus
Fathead minnow,
Plmephales promelaa
Bluegll},
Leporols tnacrochlrua
48 hrs	ETC*
8 hrs	A21 mortality
192 hrs	LCSO
1 vk	Flavor Impairment
60 Shunuay & Palenaky, 1973
31,100 Gersdorff & Smith, 1940
6,340 Phlppa, et al. Manuscript
2,000 Henderson, et al. 1960 .
* ETC  the highest estimated concentration of material that will not Impair the flavor of
flesh of exposed fish.

-------
SALTWATER ORGANISMS
Introduction
No data on the effects of 2-chlorophenol on saltwater
aquatic life are available.
B-12

-------
CRITERION FORMULATION
Saltwater - Aquatic Life
No saltwater criterion can be derived for 2-chlorophenol
using the Guidelines because no Final Chronic Value for
either fish or invertebrate species or a good substitute
for either value is available, and there are insufficient
data to estimate a criterion using other procedures.
B-13

-------
REFERENCES
Gersdorff, W.A., and L.E. Smith. 1940. Effect of introduc-
tion of the halogens into the phenol molecule on toxicity
to goldfish. I. Monochlorphenols. 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.
of photosynthetic reoxygenation.
Lab. PB 216-729.
Effects of toxic organics
Environ. Health Eng. Res.
Kopperman, H.L., et al. 1974. Aqueous chlorination and
ozonation studies. I. Structure-toxicity correlations of
phenolic compounds to Daphnia magna. Chem. Biol. Interact.
9: 245.
Lammering, M.W. , and N.C. Burbank. 1960. The toxicity
of phenol, o-chlorophenol and o-nitrophenol to bluegill
sunfish. Eng. Bull., Purdue Univ. Eng. Ext. Serv. 106: 541.
Phipps, G.L., et al. The acute toxicity of phenol and sub-
stituted phenols to the fathead minnow. (Manuscript).
B-14

-------
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. EPA-R3-73-010.
U.S. Environ. Prot. Agency, U.S. Government Printing Office,
Washington, D.C.
U.S. EPA. 1978. In-depth studies on health and environ-
mental impacts of selected water pollutants. Contract No.
68-01-4646. U.S. Environ. Prot. Agency.
B-15

-------
2-CHLOROPHENOL
Mammalian Toxicology and Human Health Effects
EXPOSURE
The potential for exposure of man to any synthetic
chemical exists through any of several modes. These modes
include: 1) exposure of industrial workers during synthe-
sis, formulation, packaging or transport; 2) exposure 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 metabo-
lite of some other product.
To understand route of entry of a chemical, one must
first, examine the sources and. properties of the material.
2-Chlorophenol is a commercially produced chemical
used as an intermediate in the production of other chemi-
cals and it represents a basic chemical feedstock for manu-
facture of higher chlorophenols.
Direct chlorination leads to the formation of both
2- and 4-chlorophenols and the isomers are separated by
fractional distillation since the difference in boiling
points is greater than 40 degrees C. Most of the 2-chloro-
phenol used commercially in the U.S.A. is recovered as
a by-product from the manufacture of 4-chlorophenol by direct
chlorination of phenol.
C-l

-------
The chlorination of phenol in aqueous solutions to
form 2-chlorophenol and higher phenols has been demonstrated
under conditions similar to those used for disinfection
of waste water effluents and may represent a source of con-
tamination (Aly, 1968; Barnhart and Campbell, 1972). Since
chlorine and phenol do not normally occur in stoichiometric
amounts, the concentrations of 2-chlorophenol actually pro-
duced in H2O are likely to be lower than those found in
this study (Weber, 1972). Higher levels of chlorination
become increasingly less favored. 2-Chlorophenol has been
synthesized from phenol and chlorine at concentrations as
low as 10 and 20 mg/1, respectively, within 1 hour (Barnhart
and Campbell, 1972). Other studies have demonstrated the
formation of 2-chlorophenol (1.7 ^ig/1) and numerous other
chlorinated compounds during the chlorination of sewage
effluents and power plant cooling waters (Jolly, 1973; Jolly,
et al. 1975).

-------
synthesized from phenol and chlorine at concentrations as
low as 10 and 20 mg/1, respectively, within 1 hour (Barnhart
and Campbell, 1972). Other studies have demonstrated the
formation of 2-chlorophenol (1.7 jig/1) and numerous other
chlorinated compounds during the chlorination of sewage
effluents and power plant cooling waters (Jolly, 1973; Jolly,
et al. 1975).
Most 2-chlorophenol produced in the U.S.A. is used
in the synthesis of higher chlorophenols (Doedens, 1963).
It can be used as an intermediate polymer in the manufacture
of fire retardant varnishes and to provide rot resistance
and crease recovery for cotton fabric. Its use in fire
retardants has largely been supplanted by bromide compounds.
2-Chlorophenol has pesticidal and bactericidal properties
but is rarely used due to availability of more effective
compounds.
The chemical and physical properties of a substance
largely determine how it will behave within organisms and
in the environment. With an empirical formula CgHgOCl,
2-chlorophenol has a molecular weight of 128.56, a specific
gravity of 1.2573 at 25 degrees, and a vapor pressure of
1 mm Hg at 12.1 degrees C (Sax, 1975: Stecher, 1968). It
melts at 8.7 degrees C and boils at 175-176 degrees C (Rodd,
1954; Judson and Kilpatrick, 1949). The chemical structure
for 2-chlorophenol is as followss
:^T'
r.

-------
It is slightly soluble in 20 degrees C water (28.5 g/1),
but quite soluble in organic solvents such as benzene, ethanol
and ether (2000 grams/liter). It is weakly acidic, with
a pKa of 8.48 in water at 25 degrees C, and will dissociate
in alkaline solutions (Judson and Kilpatrick, 1949; Pearce
and Simpkins, 1968). The monovalent salts are soluble in
aqueous solutions and the degree of solubility is pH depen-
dent.
C-4

-------
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 solubility
and if they are introduced or formed in situ they would
exist primarily in the dissolved form. Chlorophenols being
weak acids tend to ionize, depending upon the pH of the sys-
tem. They are almost completely nonionized in aqueous solu-
tion with pH lower than 5 and become increasingly dissociat-
ed as the pH rises (Cserjesi, 1972).
There is no information on amounts of 2-chlorophenol
present in finished water for human consumption.
In one study, industrial waste discharge was the prin-
cipal point source of water pollution. During the manufac-
ture of chlorophenols and 2,4-D there is chemical waste .
generated resulting from 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 herbicides showed amounts
of 2-chlorophenol ranging from a trace to 6 percent (Sid-
well, 1971) (Tables 1 and 2) of the total phenols and chloro-
phenols .
Other possible point sources are chemical spills and
washing of containers or drums in which chlorophenols and
2,4-D are stored.
C-5

-------
TABLE 1
Chlorophenols in Industrial Plant Waste
Date
25
January
3 March
21
April
28 May
27 August
Temp. C

12
18

21
28.5
24
PH

7.5
7.6

7.4
7.4
7.0
Chlorophenols
(mg/1)
68
118

125
112
74
Phenoxy Acids
(mg/1)
167
183

241
235
199
Total Solids
(mg/1) 6,
, 960
40,100
76
,320
104,860
11,000
Contamination of water with 2-chlorophenol may arise from
1) chlorination of phenol present in natural water and prim-
ary and secondary effluents of waste treatment plants (Burtt-
\
schell, et al. 1959; Eisenhauer, 1964; Barnhart and Camp-
bell, 1972), 2) direct addition of the chemicals or as contam-
inants or degradation products of 2,4-D used for aquatic
weed control, and 3) wet and dry atmospheric fallout.
C-6

-------
TABLE 2
Relative Chlorophenol Content of Industrial Waste
Date
25 January
3 March
21 April
28 May
27 August
Phenol Type
%
%
%
%
%
2-chloro
2.9
6.1
trace
trace
trace
phenol
3.4
6.2
1.7
24.8
trace
2,6 DCP
9.9
41.7
38.8
30.5
3.0
2,5 DCP
trace
6.2
1.7
trace
1.8
2,4 DCP
73.6
17.9
20.0
11.4
89.0
2,4,6 TCP
2.8
9.9
19.5
13.3
3.4
4-chloro
2.5
12.1
18.3
20.0
2.8
2,4,5 trichloro
4.7
trace
trace
trace
trace
No direct data were found to show actual measured concen-
trations of 2-chlorophenol in water courses, impoundments,
wells or other human water supply sources.
Based on the relatively limited sources of water con-
tamination 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 indicates that the dissipation of
2-chlorophenol (Ettinger and Ruchhoft, 1950) is largely
microbiological. Persistence appears to be short but limno-
logical factors such as oxygen deficiency may delay degra-
dation (Aly and Faust, 1964). Microorganisms found in acti-
vated sludge and waste lagoons have been demonstrated to
degrade the 2-chlorophenol rather readily (Sidwell, 1971;
Nachtigall and Butler, 1974).

-------
Ettinger and Ruchhoft (1950) found that low concentra-
tions (1 mg/liter) of 2-chlorophenol added to a usual dilu-
tion of domestic sewage were not removed during periods
of 20 to 30 days, presumably due to the absence of micro-
organisms capable of attacking the chemical, when a similar
concentration was added to polluted river waters the com-
pound dissipated in 15 to 23 days. Addition of a seed con-
sisting of water from a previous persistence experiment
increased significantly the removal of 2-chlorophenol.
Apparently, the seed introduced some organisms already adapt
ed 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 for the dechlor-
ination of 2-chlorophenol and other monochlorophenols within
3 days when exposed to an activated sludge system (See Table
3).
C-8

-------
TABLE 3	a b
Degradation of Chlorophenols in Acclimated Activated Sludge ' .
Amount of ring degrada-
tion of compound Development of chloride ion
Compound
%
days
%
days
2-chlorophenol
100
3
100
4
3-chlorophenol
100
2
100
3
4-chlorophenol
100
3
100
3
2,4-DCP
100
5
100
5
2,5-DCP
52
4
16
4
2,4,6-TCP
100
3
75
3
NaPCP
0
4
0
4
Dichloroquinone
100
1
50
3
2,5-DCP benzoquinone
30
1
0
1
?Source: Modified from Ingols, et al. (1966)
Concentration of 100 mg/1
Primary treatment consists essentially of settling
solids after screening off large materials. Settling may
not remove 2-chlorophenol from water because these chemicals
are sorbed 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-DCP are known to be easily biodegrad-
able, secondary treatment should provide excellent removal
of these chemicals.
Baird, et al. (1974) employing Warburg respiratory
techniques demonstrated that biodegradation of 2-chloro-
phenol at 1 mg/liter in activated sludge was complete within
3 hours. Increasing the concentration to 100 mg/liter consider-
ably reduced the rate of respiration such that only 20 percent
was degraded in 6 hours. This is probably due to microbial
toxicity from 2-chlorophenol at this concentration. In
C-9

-------
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 if waste containing high
levels of the chemical is discharged to an unacclimated
body of water due to direct or indirect toxic effects.
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 con-
ducted measuring the 2-chlorophenol content in waters re-
ceiving 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 foods. In all
cases, any contamination is probably indirect and a result
primarily of use and subsequent metabolism of phenoxyalk-
anoic herbicides.
In 1971, U.S. farmers applied almost 16,000,000 kg
of 2,4-D representing 15 percent of all organic herbicide
usage (U.S.D.A., 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 degrad-
ation is the apparent major avenue of dissipation for these
chemicals in soils. For 2,4-DCP, which is more likely to
reach the soil system as a contaminant and degradation pro-
duct of 2,4-D, its degradation under field conditions could
C-10

-------
be faster than the herbicide. The role of microorganisms
in the degradation of 2,4-D has been conclusively demonst-
rated (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 proliferation of microorganisms
known to metabolize 2,4-D. One of the steps in the meta-
bolic scheme may be 2-chlorophenol. Limited information
indicates the biodegradability of 2-chlorophenol (Walker,
1954; Baird, et al. 1974). Several genera of bacteria iso-
lated from soil are capable of 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 intermediate was elucidated from a study
of the metabolism of 2,4-D by Pseudomonas sp. (Evans, et
al. 1971). Using 2,4-D as sole carbon source for Pseudo-
monas strains isolated from soil, the herbicide was metabo-
lized to 2,4-DCP, 2-chlorophenol, 3,5-dichlorocatechol and
alpha-chloromuconate which was further metabolized to re-
lease CI" and unidentified metabolites. The appearance
in culture of 2-chlorophenol suggests the non-oxidative
elimination of chlorine from 2,4-DCP or possibly 2,4-D it-
self. The accumulation of alpha-chloromuconate is probably
a further manifestation of this phenomenon since it is like
ly formed by enzymatic cleavage of 3-chlorocatechol, the
latter, in turn, being derived from either 2-chlorophenol
or 3,5-dichlorocatechol.
It is probable that the sorption behavior of 2-chloro-
phenol is similar to 2,4-D. In natural soil systems, sorp-
C-ll

-------
tion may not be extensive thereby favoring their 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 per-
colate through 100 g of a Rothamsted soil (light clay with
a pH of 6.8) and the disappearance of the initial and sub-
sequent 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 evidence
of microbial decomposition was indicated by the more rapid
disappearance of 2-chlorophenol in fresh than in sterilized
soil within 7 days of percolation.
Furthermore, the participation of soil microorganisms
in the dissipation 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 addi-
tions of the compounds than initial enrichments. Also,
inhibition of degradation occurred on addition of sodium
azide, a toxic agent. 2-Chlorophenol disappeared 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 avail-
able studies of 2,4-dichlorophenol in plants and from the
potential for 2-chlorophenol to occur as a metabolic interme-
diate in the degradation of 2,4-D.
C-12

-------
The metabolism of 2-chlorophenol in vascular plants
is not well studied. The only report found demonstrated
that 2-chlorophenol may be inactivated by glycoside forma-
tion in plant tissue. It has been demonstrated that when
certain non-naturally 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-chlorophenol in
tomato plants included glycoside formation. Beta-o-chloro-
phenyl-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 pesticides or drink water contaminated directly
with 2-chlorophenol and 2,4-DCP. Although some studies
indicate the appearance and distribution of 2,4-DCP in tis-
sues of animals and poultry fed with 2,4-D and nemacide
(0(2,4-Dichlorophenol) 0,0-Diethyl Phosphorothioate)) (Clark,
et al. 1975; Sherman,et al. 1972), in none of the studies
was there evidence cited to indicate residues of 2-chloro-
phenol. Furthermore, Bjerke, et al. (1972) reported no
contamination of milk and cream from cows dosed with 2,4-D
(100 to 1,000 mg/kg) treated foods.
A bioconcentration factor (BCF) relates the concentration
of a chemical in water to the concentration in aquatic organ-
isms, but BCF's are not available for the edible portions
C-13

-------
of all four major groups of aquatic organisms consumed in
the United States. Since data indicate that the BCF for
lipid-soluble compounds is proportional to percent lipids,
BCF's can be adjusted to edible portions using data on percent
lipids and the amounts of various species consumed by Ameri-
cans. A recent survey on fish and shellfish consumption
in the United States (Cordle, et al. 1978) found that the
per capita consumption is 18.7 g/day. From the data on
the 19 major species identified in the survey and data on
the fat content of the edible portion of these species (Sid-
well, et al. 1974), the relative consumption of the four
major groups and the weighted average percent lipids for
each group can be calculated:
Consumption Weighted Average
Group	(Percent)	Percent Lipids
Freshwater fishes	12	4.8
Saltwater fishes	61	2.3
Saltwater molluscs	9	1.2
Saltwater decapods	18	1.2
Using the percentages for consumption and lipids for each
of these groups, the weighted average percent lipids is
2.3 for consumed fish and shellfish.
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 2.3/1.0 =2.3 can be used to adjust the measured
BCF from the 1.0 percent lipids of the bluegill to the 2.3
percent lipids that is the weighted average for consumed
fish and shellfish. Thus, the weighted average bioconcentra-
C-14

-------
tion factor for 2-chlorophenol and the edible portion of
all aquatic organisms consumed by Americans is calculated
to be 214 x 2.3 = 490.
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 degrees C) any 2-
chlorophenol generated as a decomposition product of 2,4-
D could be subject to general environmental dispersal wherever
2,4-D is applied. A third possibility for inhalation exposure
could be burning of containers, trash or plant material
contaminated with 2-chlorophenol. No data addressing the
monitoring of air or workplace environments for 2-chlorophenol
has been found. Therefore, the potential sources for in-
halation exposure remain speculative. However, the relative
potential for exposure should be considered.
Because of the processes employed in manufacture of
2-chlorophenol as well as its volatility, the most probable
source of inhalation exposure to 2-chlorophenol would occur
in manufacturing plants producing 2-chlorophenol or possibly
2,4-D. In addition, 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.
C-15

-------
Although inhalation exposure to 2-chlorophenol associ-
ated with related products in general use (2,4-D herbicide)
does not seem likely, no data to verify atmospheric 2-chloro-
phenol 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 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 then 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 microorgan-
isms (see section on Ingestion) while 2-chlorophenol in
plants is inactivated as a glycoside (Miller, 1941).
A third potential route of exposure, burning of chloro-
phenol-containing products, has not been studied. Incinera-
tion of phenoxy herbicides should include investigations
of potential formation and/or dispersal of 2-chlorophenol
as well as other chlorophenols.
While direct studies of potential or actual exposure
to 2-chlorophenol have not been found, after considering
the nature of production, uses and persistence of 2-chloro-
phenol, inhalation exposure of the general population does
not seem a significant threat.
Dermal
2-Chlorophenol dermal absorption data have not been
found. Since the compound is lipid soluble and likely to
be poorly ionized at environmental pH (Farquaharson, et
al. 1958) it should be readily absorbed through intact skin.
C-16

-------
The dermal absorption and resultant body burden should be
studied.
As indicated for inhalation exposure, the only potent-
ially significant dermal exposure to 2-chlorophenol would
be in the manufacture or handling of 2-chlorophenol or prod-
ucts which contain it. Ordinary and accepted methods of
skin protection would be expected to prevent dermal exposure
to 2-chlorophenol. Dermal exposure to 2-chlorophenol from
other sources (soil, water, plant metabolites of 2,4-D)
is considered 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. Chloro-
phenol compounds are generally considered readily absorbed
and this would be expected from their high lipid solubility
and low degree of ionization at physiological pH (Doedens,
1963; Farquharson, et al. 1958). Although skin irritation
and dermal absorption are reported as characteristic of
monochlorophenols, direct quantitative data concerning 2-
chlorophenol irritant potential have not been found. Toxi-
city studies to be discussed later indicate that 2-chloro-
phenol can be absorbed and can result in toxicosis. How-
ever, quantitative data for 2-chlorophenol absorption by
various routes have not been found.
2-Chlorophenol may occur in mammals indirectly as a
metabolite of other compounds. Exposure of rabbits to chloro-
benzene has resulted in formation of 2-chlorophenol (Lindsay-
Smith, et al. 1972).
C-17

-------
In addition, Selander, et al. (1975) reported the con-
version of chlorobenzene to a mixture of monochlorophenols
in perfused rat liver. Apparently, 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 metabo-
lite of such exposure, while 2,4-DCP is considered the major
metaboli te.
Distribution
Direct information about the distribution and transport
of 2-chlorophenol is not available. However, at least two
reports (Spencer and Williams, 1950; Von Oettingen, 1949)
on the rabbit and dog respectively, indicate urinary excre-
tion 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 about hepatic excretion nor any indication
of an enterohepatic cycle was found. While compounds of
high lipophilia (which would include 2-chlorophenol) are
often considered to accumulate in adipose tissue, no informa-
tion in this regard was found for 2-chlorophenol. In fact,
related compounds (2,4-Dichlorophenol, Pentachlorophenol)
are considered to have relatively short half-lives (Clark,
C-18

-------
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, 1958; Angel and
Rogers, 1972) it can be assumed the compound traverses the
blood brain barrier and is distributed in part in the CNS.
The concentrations of 2-chlorophenol in brain and other
organs or tissues during toxicosis remain to be determined.
Metabolism
The metabolism of 2-chlorophenols in man is not known.
In experimental animals Von Oettingen (1949) cites work
by Karpow (1893) showing that dogs excreted 87 percent of
administered 2-chlorophenol as conjugates with sulfate and
glucuronic acid. The rabbit also apparently conjugates
the 2-chlorophenol derived from chlorobenzene exposure (Lind-
say-Smith, et al. 1972) by formation of sulfate and glucu-
ronide conjugates. However, 2-chlorophenol was reported
as a minor metabolite of chlorobenzene in the rabbit (see
Table 4). Furthermore, only a minor portion of chlorophe-
nols formed were monochlorophenols and less than 6 percent
of free and metabolized chlorophenols were the ortho- or
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 noncellular systems including micro-
somes, post-mitochondrial supernatant, and reconstituted
soluble hemoprotein-monoxygenase systems. Pretreatment
C-19

-------
TABLE 4
Lethal Doses of 2-Chlorophenol for Experimental Animals3
(LD-50 in mg/kg)
Animal
Route of administration
LD-50 Author
Rat
Rat
Albino rat
Rabbit
Rabbit
Mouse
Guinea pig
Blue fox
Unknown mammal
Oral
Subcutaneous
Intraperitoneal
Subcutaneous
Intravenous
Oral
Subcutaneous
Oral
Oral
2-Chlorophenol
670
950
230.
950
120b
670.
800
440
440
Deichmann, 1943
Deichmann, 1943
Farquharson, et al. 1958
Christensen & Luginbyhl,
1975
Von Oettingen, 1940 citing
Kuroda (1926)
Bubnov, et al. 1969
Christensen & Luginbyhl,
1975
Bubnov, et al. 1969
Christensen & Luginbyhl,
1975
^Source: Assembled from several sources listed in body of the table.
MLD (minimum lethal dose) values.
with the inducing agents 3-methylcholanthrene and pheno-
barbital increased the formation of chlorophenols while
carbon monoxide and SKF 525a inhibited formation of o-,
m-, and p-chlorophenols. The approximate ratios iji vivo
for formation of o-, m-, and p-chlorophenol were 1:2:4
respectively. Thus, formation of 2-chlorophenol via metab-
olism from chlorobenzene dose not appear a significant or
major route of exposure. While it is possible that 2-chloro-
phenol could form in man or animals as a result of exposure
to phenoyxacetic acid herbicides, there are no data to support
this conjecture. In fact, Clark, et al. (1975) in studying
the metabolism of phenoxy herbicides reported the major
metabolite to be 2,4-DCP and did not mention detection of
2-chlorophenol.
C- 20

-------
Based on experimental work in two species (dogs and
rabbits) it appears that mammalian metabolism of 2-chlorophenol
follows the expected route for phenol metabolism, i.e. for-
mation of conjugates of glucuronides and sulfates with detec-
tion of these metabolites primarily in the urine.
Excretion
Studies of the excretion route or rate for 2-chloro-
phenol in man were not found. 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 develop-
ed from which rate of excretion or half-life could be cal-
culated. Lindsay-Smith, et al. (1972) identified phenolic
metabolites in rabbits urine after administration of chloro-
benzene. Of the free and conjugated forms of chlorophenols
in rabbit urine, less than 6 percent were present as 2-chloro-
pehnol.
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 oxidative uncoupler (Mitsuda, et al. 1963) and a
convulsant poison (Farquharson, et al. 1958; Angel and
Rogers, 1972). No reports of the subacute or chronic toxi-
city of 2-chlorophenol have been found. This represents
C- 21

-------
a serious data gap in the toxicologic evaluation of 2-chloro-
phenol.
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-chloro-
phenol. Furthermore, there is no evidence linking 2-chloro-
phenol exposure in industrial workers to the chloracne often
associated with higher chlorophenols. Nor is there evidence
to suggest, that the toxic dioxins are contaminants of or
are formed from 2-chlorophenol. No reports of chronic toxi-
city studies in domestic or laboratory animals have been
found.
Doedens (1963) briefly characterizes the toxicity of
2-chlorophenol as being "likely" to be corrosive
and irritating to eyes and skin. However, specific data
or effects due to 2-chlorophenol were not presented. The
only toxicologic data from which evaluation of 2-chlorophenol
can be made result from a relatively few acute toxicologic
studies in laboratory mammals (see Table 4). It may be
seen by inspection of Table 4 that the subcutaneous minimum
lethal dose (MLD) of 2-chlorophenol in the rabbit (800 to
950 mg/kg) is approximately 8 times that of the intravenous
MLD implying that the subcutaneous route retards bioavaila-
bility of 2-chlorophenol. At a physiological pH of 7.4,
2-chlorophenol will be approximately 5 percent ionized
(Farquharson, et al. 1958) which would not account for
a lessening of toxicity by the subcutaneous route.
C- 22

-------
The oral LD50 indicates that 2-chlorophenol is more toxic
by the oral than the subcutaneous route. At relatively
acid pH (e.g. stomach or intestine) the pKa of 2-chlorophenol
(8.65) would allow for a highly unionized state with ready
absorption from the stomach or upper intestine. This effect
could explain the greater toxicity of 2-chlorophenol orally.
Among the various species tested by the same route
there is surprising similarity of acute toxicity. This
would imply that initial absorption, metabolism, detoxifica-
tion and organs affected 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 simi-
lar whether the compound is administered subcutaneously,
intraperitoneally, or orally. The toxicological picture
includes restlessness and increased rate of respiration
within a few minutes 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 tubules, fatty infiltration in the liver
C- 23

-------
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-chloro-
phenol caused fatty degeneration of the liver, renal gran-
ular dystrophy and necrosis of the stomach and intestinal
mucose. These signs are very similar to acute phenol toxi-
cosis (Patty, 1963).
The convulsive action of 2-chlorophenol in mice was
studied by Angel and Rogers (1972). Following intraperi-
toneal administration of 2-chlorophenol, 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 CNS by a simple
chemical reaction. However, no information directly address-
ing this point is available.
Farquharson, et al. (1958) state that as phenol is
progressively chlorinated the molar toxicity shows a tend-
ency to increase when pK value falls below 7. Furthermore,
convulsions are the most characteristic effect of chloro-
phenols with pK values of 8.65 or higher. Thus, it may
be that convulsions are in some way associated with undisso-
ciated molecules. No studies were found which attempted
to evaluate the passage of chlorophenols with different
pK values across the blood brain barrier.
C- 24

-------
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 oxidative uncoupl-
er (Mitsuda, et al. 1963) it may be expected that concomi-
tant exposure to other uncouplers (e.g. pentachlorophenol,
dinitrophenol) would enhance that effect. In addition,
exposure to chlorinated hydrocarbon insecticides with their
characteristic convulsant activity could be at least add-
itive in that regard.
Any agent causing liver damage sufficient to decrease
the conjugation of 2-chlorophenol with glucuronide or sul-
fate 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 speculation
that the general tendency of conjugation to render a com-
pound less toxic and more amenable to excretion would also
operate in the case of 2-chlorophenol.
Teratogenci ty
No studies were found which addressed the teratogeni-
city of 2-chlorophenol.
Mutagenicity
No studies were found which addressed the mutagenicity
of 2-chlorophenol.
C- 25

-------
' Carcinogenicity
The report of Boutwell and Bosch (1959) is the only
one found dealing with tumorigenicity of 2-chlorophenol.
Repeated application of phenol and some substituted phenols
has been reported to promote skin tumors in mice after a
single initiating dose of dimethylbenzanthracene (DMBA).
Papillomas have developed in mice (not exposed to DMBA)
treated with phenol alone. In the studies of Boutwell and
Bosch (1959) two trials included evaluation of 2-chlorophe-
nol. In one of these, 25 pi of a 20 percent solution of
2-chlorophenol was applied twice weekly to female Sutter
mice 2-3 months of age for 15 weeks. This application followed
an initiating dose of 0.3 percent DMBA in benzene.
Tumorigenic response was measured as follows:
1)	The percentage of surviving mice bearing one or
more papilloma was ascertained.
2)	The total number of papillomas on all surviving
mice was counted and divided by the number of
survivors 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 com-
parative purposes. Based on the data, the authors concluded
that the promoting activity of 2-chlorophenol is similar
to that of phenol.
C-26

-------
TABLE 5
Appearance of Skin Tumors in Mice Treated Cutaneously With Phenols Following a
Cutaneous Dose of 0.3% Dimethyl Benzanthracene (DMBA) in Acetone .
Treatments
Time animals
examined
(week)
Survivors	Average
No. of mice with papilloma papillomas
(survivors/total)	(%)	per survivor
Survivors with
epithelial carcinoma
(%)
Benzene control	12
10% phenol in
benzene. No DMBA	20
20% phenol in
- ace tone	12
20% phenol in
benzene	24
20% 2-chlorophenol
in benzene	15
20% 2-chlorophenol
in dioxane. No DMBA 12
12/12
24/30
21/24
10/33
31/35
28/30
0
33
58
100
61
46
0
0. 62
3. 20
1. 48
0.64
0
13
5
20
10
fSource: Modified from Boutwell and Bosch, 1959.
All received DMBA except where stated.

-------
In a second experiment, Boutwell and Bosch (1959) admin-
istered 20 percent 2-chlorophenol in dioxane as before for
12 weeks, but without an initiator. Results of this trial
are also in Table 5. In both trials 2-chlorophenol was
associated with a high incidence of papillomas. When DMBA
was used as an initiator 10 percent of the survivors develop-
ed carcinoma at the skin site of application. When 2-chloro-
phenol alone was used there was no carcinogenic response.
Since the study was designed primarily to detect promot-
ing activity, the effect of 2-chlorophenol as a primary
carcinogen is not well defined. The study uses dermal appli-
cations of a phenolic compound at 20 percent concentration
in organic solvents. The concentration is high enough that
hair follicles and sebaceous glands are destroyed. The papil-
lomatous 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 malig-
nant neoplasia are observed except when DMBA had been used
as an initiator. The only neoplasia observed was at the
site of the direct application. This study does not eval-
uate systemic carcinogenesis and the route of administration
is not appropriate to the model for carcinogenic risk assess-
ment. The route of administration (dermal) has no establish-
ed relationship to oral exposure.
An odor threshold for 2-chlorophenol in water has been
reported by at least two investigators. Hoak (1977) deter-
mined the odor threshold of 2-chlorophenol to be 0.33 pg/1
at 30C and 2.5 jig/1 at 60C. Determination of the detect-
C-28

-------
able odor was made by a panel of from two to four people
comparing flasks of test water to a flask of odor-free water.
The lowest concentration detected by any panel member was
taken as the odor threshold. 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 30C while others were higher at 60C.
Burtschell, et al. (1959) made dilutions of chlorophenol
in carbon-filtered tap water and used a panel of from four
to six people to evaluate odor. Tests were carried out
at room temperature which the investigator estimated to
be 25C. If a panel member's response was doubtful, the
sample was considered negative. The geometric mean of the
panel responses was used as the odor threshold. The data
presented do not indicate a range of responses, but owing
to the variability inherent to such procedures, it seems
reasonable that the odor threshold for some people in the
Burtschell group estimated downward toward the 0.33 jjg/1
figure of Hoak.
Studies on the impairment of fish flavor by 2-chloro-
phenol have also been reported. Henderson, et al. (1961)
found that a concentration of 2,000 jig/1 caused impaired
flavor of bluegill sunfish after a 28-day static, renewal
exposure. Only one concentration was tested, so no dose-
related threshold was determined. Shumway and Palensky
(1973) found 60 ^g/1 to be an estimated threshold concentra-
tion during a 48-hour flow-through exposure to rainbow trout.
C- 29

-------
Shultz (1961) determined that 15 ^g/1 affected the flavor
of carp after a 3-day flow-through exposure. Boetius (1954)
studied the flavor impairment of eels and oysters (species
unspecified) in static systems and found flavor impairment
in brackish water at 0.125 pg/1 after 11 days for eels and
4 days for oysters. Methodology for determining flavor
impairment was particularly lacking in the Boetius paper.
Because of the subjectivity of flavor impairment, test meth-
odology (especially in the selection of and evaluation by
the test panel) is particularly important for the critical
evaluation of a flavor impairment study.
C-30

-------
CRITERION FORMULATION
Existing Guidlines and Standards
As far as can be determined, no standards or guidelines
exist for 2-chlorophenol.
Current Levels of Exposure
Overall, exposure of the general population to 2-chloro-
phenol would be most likely in the form of consumption
of phenolic-containing chlorinated 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 2-chlorophenol are available. Apparently,
such monitoring is not generally being done.
Since 2-chlorophenol is not a universally reported
metabolite of 2,4-D, exposure of the general population
via use of 2,4-D is only speculative. If small amounts
of 2-chlorophenol are formed and gain access to ground water
or the soil, it is not expected to persist in view of its
ready susceptibility to microbial attack.
Inhalation or dermal exposure to the general population
is not expected to be a significant part of any total 2-
chlorophenol exposure.
For industrial workers manufacturing or handling 2-
chlorophenol, inhalation exposure could be the greatest
threat and the hardest to control. Dermal exposure in such
instances should be negligible if sensible and accepted
industrial hygiene practices are followed.
Due to the lack of monitoring data or human body burden
values, human exposure cannot be determined.
C-31

-------
Special Groups at Risk
The only special group expected to be at risk for high
exposure to 2-chlorophenol are industrial workers involved
in manufacturing 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 carcinogenic agent. The only study performed (Boutwell
and Bosch, 1959) was designed to detect the promoting activity
of 2-chlorophenol with dimethylbenzanthracene initiated
tumors. (Under certain environmental conditions, 2-chloro-
phenol may produce a small amount of dibenzo-p-dioxin, which
is an unsubstituted analog of chlorinated dibenzo-p-dioxins.
The recent NCI bioassay report of possible carcinogenicity
of dibenzo-p-dioxin'3/ has concluded that dibenzo-p-dioxin
was not carcinogenic for Osborne-Mendel rats or B6C3F1 mice.)
In fact, insufficient health effects data exist on any chronic
or acute effect of 2-chlorophenol. In view of this, the
recommended criterion is based on organoleptic effects.
The data of the two investigators evaluating the odor
of 2-chlorophenol in drinking water indicated that a low
concentration is capable of causing discernible odor. Neither
worker indicated if the threshold odor concentration made
the water unacceptable for consumption. These studies coupled
with flavor impairment studies suggest that the selection
of 0.3 pq/1 2-chlorophenol would be sufficient for the preven-
tion of adverse organoleptic effects in water. It should
C- 32

-------
be emphasized that this is a criterion based on aesthetic
rather than health effects. Data on human health effects
need to be developed as a more substantial basis for setting
a criterion for the protection of human health.
Thus, based on the prevention of adverse organoleptic
effects, the interim criterion recommended for 2-chloro-
phenol is 0.3 jug/1.
C-33

-------
REFERENCES
Alexander, M., and M.I.H. Aleem. 1961. Effect of chemical
structure on microbial decomposition of aromatic herbicides.
Jour. Agric. Food Chem. 9: 44.
Aly, O.M. 1968. Separation of phenols in waters by thin
layer chromatography. Water Res. 2: 587.
Aly, O.M., and S.D. Faust. 1964. Studies on the fate of
2,4-D and ester derivatives in natural surface waters.
Jour. Agric. Food Chem. 12: 541.
Angel, A., and K.J. Rogers. 1972. An analysis of the con-
vulsant activity of substituted benzenes in the mouse.
Toxicol. Appl. Pharmacol. 21: 214.
Baird, R.B., et al. 1974. The fate of phenolics in wastewater.
Determination by direct-injection GLC and Warburg respirometry.
Arch. Environ. Contain. Toxicol. 2: 165.
Barnhart, E.L., and G.R. Campbell. 1972. The effect of
chlorination on selected organic chemicals. U.S. Government
Printing Office, Washington, D.C.
Binet, P. 1895. Comparative toxicity of phenols. Rev.
Mid. Suisse Rom. 15: 561.
C-34

-------
Bjerke, E.L., et al. 1972. Residue study of phenoxy herbicides
in milk and cream. Jour. Agric. Food Chem. 20: 963.
Boutwell, R.K., and D.K. Bosch. 1959. The tumor-promoting
action of phenol and related compounds for mouse skin.
Cancer Res. 19: 413.
Bubnov, V.D., et al. 1969. Toxic properties of activated
o-chlOrophenol for white mice and blue foxes. Tr., Vses.
Nauchno-Issled. Inst. Vet. Sanit. (Moscow). 33: 258.
Burttschell, R.H., et al. 1959. Chlorine derivatives of
phenol causing taste and odor. Jour. Am. Water Works Assoc.
51: 205.
Christensen, H.E. and T.T. Luginbyhl. 1975. Registry of
toxic effects of chemical substances. U.S. Pub. Health
Serv., Center for Dis. Control, Rockville, Md.
Clark, D.E., et al. 1975. Residues of chlorophenoxy acid
herbicides and their phenolic metabolites in tissues of
sheep and cattle. Jour. Agric. Food Chem. 23: 573.
Csarjesi, A.J. 1972. Detoxification of chlorinated phe-
nols. Int. Biodeterior Bull. (Birmingham, England).
8: 135.
C-35

-------
Deichmann, W.B. 1943. The toxicity of chlorophenols for
rats. Fed. Proc. 2: 76.
Doedens, J.D. 1963. Chlorophenols. Page 325 jm Kirk-
Othmer encyclopedia of chemical technology. John Wiley
and Sons, Inc., New York.
Eisenhauer, H.R. 1964. Oxidation of phenolic wastes.
Jour. Water Pollut. Control Fed. 36: 1116.
Ettinger, M.B., and C.C. Ruchhoft. 1950. Persistence of
monochlorophenols in polluted river water and sewage dil-
utions. D.S. Pub. Health Serv., Environ. Health Center,
Cincinnati, Ohio.
Evans, W.C., et al. 1971. Bacterial metabolism of 2,4-
dichlorophenoxyacetate. Biochem. Jour. 122: 543.
Farquharson, M.E., et al. 1958. The biological action
of chlorophenols. Br. Jour. Pharmacol. 13: 20.
Fieser, L.F., and M. Fieser. 1950. Organic chemistry.
2nd ed. D.C. Health and Co., Boston.
Henshaw, T.B. 1971. Adsorption/filtration plant cuts phenols
from effluent. Chem. Eng. 76: 47.
Hoak, R.D. 1957. The causes of tastes and odors in drink-
ing water. Water Sewage Works. 104: 243.
C-36

-------
Jolly, R.L. 1973. Chlorination effects on organic constitu-
ents in effluents from domestic sanitary sewage treatment
plants. Ph.D. dissertation. University of Tennessee.
Jolly, R.L., et al. 1975. Chlorination of cooling water:
A source of environmentally significant chlorine-containing
organic compounds. Proc. 4th Natl. Symp. Radioecology.
Corvallis, Ore.
Judson, C.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.
Ingols, R.S., et al. 1966. Biological activity of halophenols.
Jour. Water Pollut. Control Fed. 38: 629.
Karpow, G. 1893. On the antiseptic action of three isomeric
chlorophenols and of their salicylate esters and their fate
in the metabolism. Arch. Sci. Biol. St. Petersburg. 2: 304.
Kearney, P.C., et al. 1969. Decontamination of pesticides
in soils. Residue Rev. 29: 137.
Kirk and Othmer. 1972. Encyclopedia of chemical technology.
3rd ed. Interscience Publishers, New York.
C-37

-------
Kopperman, H.L., et al. 1974. Aqueous chlorination and
ozonation studies. I. Structure-toxicity correlations of
phenolic compounds to Daphnia magna. Chem. Biol. Inter-
act. 9: 245.
Kuroda, T. 1962. Comparative studies on the action of
o-, ra-, and p-chlorophenol. Arch. Exp. Path. Pharmakol.
112: 60.
Lee, G.F., and J.C. Morris. 1962. Kinetics of chlorination
of phenolchlorophenolic tastes and odors. Int. Jour. Air
Water Pollut. 6: 419.
Lindsay-Smith, J.R., et al. 1972. Mechanisms of mammalian
hydroxylation: Some novel metabolites of chlorobenzene.
Xenobiotica 2: 215.
Loos, M.A. 1975. Phenoxyalkanoic acids. Page 1 ^n
P.C. Kearney and D.D. Kaufman, eds. Herbicides. Marcell
Dekker, Inc., New York.
Mann, H. 1951. Zur Frage der Geshmackbein-Flussungbein
Fischen. Fischwirt 1: 164.
Miller, L.P. 1941. Induced formation of a B-gentiobioside
in tomato roots. Contrib. Boyce Thompson Inst. 11: 387.
Mitsuda, H., et al. 1963. Effect of chlorophenol analogues
on the oxidative phosphorylation in rat liver mitochondria.
Agric. Biol. Chem. 27: 366.
C-38

-------
Muller, H. 1962. Die Wirkung der Abwassereinleitungen
auf den Fischbestand der Fliessender und Stenden Gewasser
in der DDP. Wissenzchaft. Z. Karl Mark Dniv., Leipz.
lis 153.
Nachtigall, H., and R.G. Butler. 1974. Metabolism of phenols
and chlorophenols by activated sludge microorganisms. Abstr.
Annu. Meet. Amer. Soc. Microbiol. 1974: 184.
National Cancer Institute. 1978. Bioassay of dibenzo-p-
dioxin for possible carcinogenicity. DHEW Publ. No. (NIH)
78-1377.
Osweiler, G.D., et al. Toxicologic and residue aspects
of pentachlorophenol. Proc. 20th Annu. Meet. Am. Assoc.
Vet. Lab. Diagnosticians. Oct. 19, 1977, Minneapolis, Minn.
Patty, F.A. 1963. Industrial hygiene and toxicology.
II. Toxicology. Interscience Publishers, New York.
Pearce, P.J., and R.J.J. Simpkins. 1968. Acid strengths
of some substituted picric acids. Can. Jour. Chem. 46:
241.
Pickering, Q.H. and C. Henderson. 1966. Acute toxicity
of some important petrochemicals to fish. Jour. Water Pol-
lut. Control Fed. 39: 1419.
C-39

-------
Rodd, E.H. 1954. Chemistry of carbon compounds. III-A.
Aromatics. Elsevier Publishing Co., Amsterdam.
Sax, H.I. 1975. Dangerous properties of industrial mater-
ials. 4th ed. Van Nostrand Reinhold Co., New York.
Schulze, E. 1961. Zur Geschmacklichen Beeinflussungen
von Fischen durch Phenolhaltige Abnasser. Int. Rev. Gesam-
ten Hydrobiol. Hydrogr. 46: 94.
Selander, H.G., et al. 1975. Metabolism of chlorobenzene
with hepatic microsomes and soluble cytochrome P450 system.
Arch. Biochem. Biophys. 168: 309.
Sherman, J., et al. 1972. Chronic toxicity and residues
from feeding nemacide (2,4-dichlorophenol) jD, ^-diethyl
phosphorothioate to laying hens. Jour. Agric. Food Chem.
23: 617.
Sidwell, A.E. 1971. Biological treatment of chlorophenolic
wastesthe demonstration of a facility for the biological
treatment of a complex chlorophenolic waste. Water Pollut.
Control Res. Ser. 12130 EKG.
Sletten, 0., and N.C. Burbank.
ing test for toxic substances.
Eng. Ext. Ser. 141: 24.
1972. Respirometric screen-
Eng. Bull. Purdue Univ.
C-40

-------
-Spencer, B., and R.T. Williams, 1950. Studies in detoxica-
tion. The metabolism or halogenobenzenes. A comparison
of the glucuronic acid, etheral sulfate, and mercapturic
acid conjugates of chloro-, bromo-and iodo-benzenes and of
the o-, m-, and p-chlorophenols. Biosynthesis of o-, m-, and p
chlorophenol glucuronides. Biochem. 47: 279.
Spokes, J.R., and N. Walker. 1974. Chlorophenol and chloro-
benzoic acid co-metabolism by different genera of soil bac-
teria. Arch. Microbiol. 96: 125.
Stecher, P.G., ed. 1968. The Merk Index. 8th ed. Merck
and Co., Rahway, N.J.
U.S. Department of Agriculture. 1974. Farmers' use of
pesticides in 1971--quantities. Agric. Econ. Rep. No. 252.
Econ. Res. Serv., Washington, D.C.
Von Oettingen, W.F. 1949. Phenol and its derivatives:
the relation between their chemical constitution and their
effect on the organism. Natl. Inst. Health Bull. 190: 193.
Walker, N. 1954. Preliminary observations on the decom-
position of chlorophenols in soil. Plant Soil 5: 194.
Watson, W.D. 1974. Chlorination of phenols with chlorine
and tert-butyl hypochlorite. A comparison. Jour. Org.
Chem. 39: 1160.
C-41

-------