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Development
HEALTH AND ENVIRONMENTAL EFFECTS DOCUMENT
FOR 2-CHLOROPHENOL
Prepared for
OFFICE OF SOLID WASTE AND
EMERGENCY RESPONSE
Prepared by
Environmental Criteria and Assessment Office
Office of Health and Environmental Assessment
U.S. Environmental Protection Agency
Cincinnati, OH 45268
DRAFT: 00 NOT CITE OR QUOTE
NOTICE
document 1s a preliminary draft. It has not been formally released
S. Environmental Protection Agency and should not at this stage be
to represent Agency policy. It 1s being circulated for comments
chnlcal accuracy and policy implications.
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DISCLAIMER
This report Is an external draft for review purposes only and does not
constitute Agency policy. Mention of trade names or commercial products
does not constitute endorsement or recommendation for use.
11
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PREFACE
Health and Environmental Effects Documents (HEEOs) are prepared for the
Office of Solid Waste and Emergency Response (OSWER). This document series
Is Intended to support listings under the Resource Conservation and Recovery
Act (RCRA) as well as to provide health-related limits and goals for emer-
gency and remedial actions under the Comprehensive Environmental Response,
Compensation and Liability Act (CERCLA). Both published literature and
Information obtained for Agency Program Office files are evaluated as they
pertain to potential human health, aquatic life and environmental effects of
hazardous waste constituents. The literature searched for 1n this document
and the dates searched are Included In "Appendix: Literature Searched."
Literature search material Is current up to 8 months previous to the final
draft date listed on the front cover. Final draft document dates (front
cover) reflect the date the document Is sent to the Program Officer (OSHER).
Several quantitative estimates are presented provided sufficient data
are available. For systemic toxicants, these Include Reference doses (RfDs)
for chronic and subchronlc exposures for both the Inhalation and oral
exposures. The subchronlc or partial lifetime RfD Is an estimate of an
exposure level that would not be expected to cause adverse effects when
exposure occurs during a limited time Interval I.e., for an Interval that
does not constitute a significant portion of the llfespan. This type of
exposure estimate has not been extensively used, or rigorously defined as
previous risk assessment efforts have focused primarily on lifetime exposure
scenarios. Animal data used for subchronlc estimates generally reflect
exposure durations of 30-90 days. The general methodology for estimating
subchronlc RfOs Is the same as traditionally employed for chronic estimates,
except that subchronlc data are utilized when available.
In the case of suspected carcinogens, RfOs are not estimated. Instead,
a carcinogenic potency factor, or q-j* (U.S. EPA, 1980), Is provided.
These potency estimates are derived for both oral and Inhalation exposures
where possible. In addition, unit risk estimates for air and drinking water
are presented based on Inhalation and oral data, respectively.
Reportable quantities (RQs) based on both chronic toxldty and cardno-
genldty are derived. The RQ Is used to determine the quantity of a hazard-
ous substance for which notification 1s required 1n the event of a release
as specified under the Comprehensive Environmental Response. Compensation
and Liability Act (CERCLA). These two RQs (chronic toxldty and cardno-
genldty) represent two of six scores developed (the remaining four reflect
1gn1tab1l1tyt reactivity, aquatic toxldty, and acute mammalian toxldty).
Chemical-specific RQs reflect the lowest of these six primary criteria. The
methodology for chronic toxldty and cancer based RQs are defined In U.S.
EPA, 1984 and 1986a. respectively.
111
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EXECUTIVE SUMMARY
2-Chlorophenol 1s a colorless to yellow-brown liquid with an unpleasant.
penetrating odor. It Is soluble 1n alcohol, ether and water (Sax and Lewis,
1987; Weast et al., 1988). A weak add, H Is freely soluble In basic
solutions (Frelter, 1981). Current production volume data were not located;
however, between 10,000 and 100,000 pounds was manufactured or Imported In
the United States In 1977 (TSCAPP, 1989). Most of the 2-chloropheno1 pro-
duced 1s either used directly 1n the synthesis of other chlorinated phenols
or as an Intermediate In the production of larger synthetic molecules.
Approximately IX of production 1s Isolated for use 1n disinfectants, resins
and other specialty products (Frelter, 1981; Scow et al., 1982).
In the atmosphere, 2-chlorophenol Is expected to exist almost entirely
1n the vapor phase (Suntlo et al., 1988). The gas-phase reaction with
photochemlcally produced hydroxyl radicals 1s expected to be rapid, with an
estimated half-life of 1.6 days (Atkinson, 1985). Nighttime degradation by
the gas-phase reaction with nitrate radicals 1s expected to be significant
In urban areas (Kanno and NoJIma, 1979). Physical removal of 2-chlorophenol
by wet precipitation may also occur. In water, photolysis and mlcroblal
degradation are expected to be significant. In basic waters, the Ionic form
of 2-chlorophenol undergoes rapid photolysis. The neutral form photollzes
more slowly (Boule et al.. 1982. 1984. 1987).
Mlcroblal degradation under aerobic (Tabak et al., 1981; Balrd et al.,
1974; Lund and Rodriguez, 1984; SuflUa and Miller, 1985) and anaerobic
(Krumme and Boyd, 1988; Battersby and Wilson. 1989; SuflUa and Miller,
1985) conditions has been demonstrated. Bloconcentratlon In aquatic
organisms 1s not expected to be significant. Volatilization from water to
1v
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the atmosphere 1s expected; however, this process may be attenuated by
adsorption to sediment and suspended matter. In soil, blodegradatlon Is
expected to be the dominant fate process. Mlcroblal degradation using a
soil Inoculum has been demonstrated under aerobic (Alexander and Aleem,
1961; Ingols et al., 1966; Haller, 1978; Klncannon and Lin, 1985) and
anaerobic (Boyd et al., 1983; Horowitz et al., 1982) conditions.
Volatilization from the soil surface to the atmosphere Is expected; however,
1t may be attenuated by the process of adsorption.
2-Chlorophenol can enter the environment as a result of Us commercial
•
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effect on biueglll or sea lamprey, Petromyzon marlnus. but produced death In
trout, Salmo galrdnerll. within 13 hours (Applegate et al.t 1957). Exposure
to concentrations <4 mg/l for 30 days had no effect on eggs and larvae of
fathead minnows In an early life stage toxldty test {LeBlanc, 1983). The
BCF determined In blueglll was 214; the elimination half-life was <1 day
(Barrows et al., 1980). Studies using freshwater Invertebrates revealed
that toxic effects occurred at concentrations similar to those found for
fish. LC50 and Immobilization ECrQ values In Daphnla ranged from 2.6-23
mg/l (Bazln et al., 1987; Oevlllers and Chambon, 1986; Keen and Balllod,
1985; Kn1e et al., 1983; Kopperman et al., 1974; LeBlanc, 1980; Randall and
Knopp, 1980; Tlssot et al., 1985; Trabalka and Bunch, 1978). The lethal
threshold was 5.3 mg/l 1n the shrimp, Crangon septemsplnosa. the only
saltwater animal studied. Among freshwater algae, EC5Q values for growth
Inhibition were 70 mg/l In Selenastrum caprlcornutum. and 170 mg/l In
Chlorella vulgarls (Shlgeoka et al., 1988). Effects In bacteria Included
50% reduction 1n light emitted by Photobacterlum phosphoreum at 14.7-40
mg/l (Bazln et al., 1987; Cunningham et al., 1986; Curtis et al., 1982;
R1bo and Kaiser, 1983), 25-27% reduction In nitrite utilization by
Nltrobacter at 50 mg/l (Wang and Reed, 1984), decreased ATP content In
Escher1ch1a coll and NUrosomonas europaea at 100-1000 mg/l (Parker and
Prlbyl, 1984) and 50% reduction In bacterial dehydrogenase activity 1n a
mixed bacterial culture at 700 mg/l. Among terrestrial organisms, the oral
LD5Q 1n red-winged blackbirds was >113 mg/kg (Schafer et al., 1983).
Chlorophenols as a class are reportedly absorbed readily from the
gastrointestinal tract and from parenteral sites of Injection (Delchmann and
Kepllnger, 1981). Orally administered 2-chlorophenol appears to be rapidly
and almost completely absorbed from the gastrointestinal tracts of rats
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(Carpenter et al., 1985; Houser, 1983) and chinchilla rabbits (Spencer and
Williams, 1950). In ^n vitro studies using human autopsy skin, 2-chloro-
phenol was absorbed by the epidermal membrane with a permeability coeffi-
cient of 5.5lxlO'Vcm/m1n (Roberts et al., 1977).
Following oral administration of 2-chlorophenol to rats, the compound
was found In the liver and kidney (Exon and Koller, 1982), but metabolism
and excretion occurred so rapidly that there was IHtle distribution to body
tissues (Carpenter et al., 1985). Urinary excretion accounted for 91% of an
oral dose In rats wUhln 24 hours of treatment (Carpenter et al., 1985).
Over 90% of the urinary excretion consisted of glucuronlde and sulfate '
conjugates of the parent compound, and <2% consisted of unchanged parent
compound (Carpenter et al., 1985). Other metabolites Identified In the
urine of treated rats Include glucuronlde and sulfate conjugates of
2-chlorohydroqu1none (Houser, 1983). an oxidation product of 2-chlorophenol.
Glucuronlde and ethereal suflate conjugates of 2-chlorophenol In the urine
of orally treated chinchilla rabbits accounted for virtually 100% of an oral
dose (Spencer and Williams. 1950).
No Information was located concerning the subchronlc or chronic Inhala-
tion toxldty of 2-chlorophenol.
In rats dosed by gavage with 2-chlorophenol at 65 or 130 mg/kg for 3
weeks, there were reductions 1n weight gains and Increases 1n liver weights
when compared with controls (Chung, 1978). Hematologlcal effects and
hepatic degeneration were also noted at both treatment levels.
In reports of a subchronlc drinking water study (Exon and Koller, 1983a,
1985) 1n which rats were exposed to 2-chlorophenol pre-, post-, and pre- and
postnatally by the dams and then In the drinking water at levels of 0, 5, 50
and 500 ppm for <15 weeks, no 1mmunolog1cal effects were observed at any
level.
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In a chronic drinking water study (Exon and Roller, 1985) In which rats
were exposed to 2-chlorophenol prenatally by their dams and then 1n the
drinking water at levels of 0, 5, 50 and 500 ppm for <2 years, hemoglobin
levels, R8C counts and PCV were all significantly higher In the groups
exposed to 500 ppm than In controls.
Chlorophenols reportedly Irritate the skin and eyes, and the dusts
Irritate the respiratory tract (FreHer, 1979). In humans, 2-chlorophenol
causes severe burns, liver and kidney damage, narcosis and respiratory
depression (Davis et al., 1959).
Oral l05Qs of 670, 346-670 and 440 mg/kg have been reported for the
rat (Delchmann, 1943), the mouse (Borzelleca et al., 1985; Bubnov et al.,
1969) and the blue fox (Bubnov et al., 1969), respectively. A single oral
dose of 300 mg/kg caused kidney and liver damage 1n Gunn rats, which
appeared to be more sensitive to the compound than Sprague-Oawley rats
(Houser, 1983). An oral dose of 63 mg/kg caused motor Impairment 1n CO-1
mice within 5 minutes, and a dose of 1 mg/kg produced behavioral change
after 2 days (Borzelleca, 1983). A gavaged dose of 175 mg/kg resulted In
80% mortality In mice, with a statistically significant weight loss before
death; hyperactlvlty was seen at lower doses (Kallman et al., 1982). In
rats, a median lethal IntraperUoneal dose of 230 mg/kg caused excited
behavior and convulsions, with a decrease 1n body temperature (Farquharson
et al.. 1958).
No Information on cardnogenldty of 2-chlorophenol from Inhalation
exposures could be located. A carc1nogen1c1ty-cocardnogen1c1ty drinking
water study (Exon and Roller, 1985) In which rats were exposed to 2-chloro-
phenol In utero and then In drinking water at concentrations <500 ppm was
negative for cardnogenlclty after 2 years of exposure. In the same study,
2-chlorophenol appeared to promote the cardnogenlcHy of ENU, Increasing
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the tumor Incidence and decreasing the t1me-to-tumor In male rats. Dermal
application of 2-chlorophenol following Initiation by DMBA promoted the
formation of skin tumors 1n mice (Boutwell and Bosch, 1959).
Up to 1000 yg/plate 2-chlorophenol was negative for mutagenlclty 1n
four strains of Salmonella typhlmurlum. with and without metabolic activa-
tion (Haworth et al., 1983). It did not Induce SCEs or affect DMA synthesis
In mice dosed with 75-300 mg/kg (Borzelleca, 1983). Chromatld deletions
were reported 1n rat bone marrow cells from treatment with 130 mg/kg every
other day for 1 week (Chung, 1978).
No Information on the teratogenldty of 2-chlorophenol could be located.
Reproductive effects were reported In rats exposed to 2-chlorophenol 1n
drinking water from weaning through breeding and lactation (Exon and Koller,
1982, 1985). Reduced Utter sizes and Increased number of stillbirths were
seen In rats exposed to 500 ppm 2-chlorophenol; these effects were not seen
at <50 ppm.
Although drinking water (Exon and Koller, 1985) and dermal (Boutwell and
Bosch, 1959) exposure studies suggested that 2-chlorophenol may be a tumor
promoting agent, data were Inadequate to Implicate the chemical as a primary
carcinogen. The chemical was assigned to U.S. EPA Group 0: not classifiable
as to cardnogenldty In humans. Ne1th«r cancer potencies nor a cancer-
based RQ were derived.
U.S. EPA (1986b) derived an RfO for chronic oral exposure of 0.005
mg/kg/day from the 24-month drinking water study using rats by Exon and
Koller (1985). This value 1s verified and available on IRIS (U.S. EPA,
1988). A chronic (noncancer) tox1cUy-based RQ of 1000 was calculated based
on reproductive effects observed 1n rats exposed to drinking water contain-
ing 500 ppm 2-chlorophenol (Exon and Koller, 1982).
1x
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TABLE OF CONTENTS
1. INTRODUCTION ' 1
1.1. STRUCTURE AND CAS NUMBER 1
1.2. PHYSICAL AND CHEMICAL PROPERTIES 1
1.3. PRODUCTION DATA 2
1.4. USE DATA 2
1.5. SUMMARY 3
2. ENVIRONMENTAL FATE AND TRANSPORT 4
2.1. AIR 4
2.1.1. Reaction with Hydroxyl Radicals 4
2.1.2. Reaction with Ozone .'.. 4
2.1.3. Photolysis : 4
2.1.4. Physical Removal Processes 4
2.2. WATER 5
2.2.1. Hydrolysis 5
2.2.2. Oxidation 5
2.2.3. Photolysis 5
2.2.4. M1crob1al Degradation 5
2.2.5. B1oconcentrat1on 6
2.2.6. Adsorption 6
2.2.7. Volatilization 6
2.3. SOIL" 7
2.3.1. M1crob1al Degradation 7
2.3.2. Adsorption 8
2.3.3. Volatilization 8
2.4. SUMMARY 8
3. EXPOSURE 10
3.1. HATER 10
3.2. FOOD 11
3.3. INHALATION 11
3.4. DERMAL 11
3.5. OTHER > 11
3.6. SUMMARY 12
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TABLE OF CONTENTS (cont.)
Page
4. ENVIRONMENTAL TOXICOLOGY 13
4.1. AQUATIC TOXICOLOGY 13
4.1.1. Acute Toxic Effects on Fauna 13
4.1.2. Chronic Effects on Fauna 16
4.1.3. Effects on Flora 17
4.1.4. Effects on Bacteria 17
4.2. TERRESTRIAL TOXICOLOGY 18
4.2.1. Effects on Fauna 18
4.2.2..J Effects on Flora 18
4.3. FIELD STUDIES 18
4.4. AQUATIC RISK ASSESSMENT 19
4.5. SUMMARY 19
5. PHARMACOKINETCS 22
5.1. ABSORPTION 22
5.2. DISTRIBUTION 23
5.3. METABOLISM 24
5.4. EXCRETION " 24
5.5. SUMMARY 25
6. EFFECTS 26
6.1. SYSTEMIC TOXICITY 26
6.1.1. Inhalation Exposure 26
6.1.2. Oral Exposure 26
6.1.3. Other Relevant Information 27
6.2. CARCINOGENICITY 29
6.2.1. Inhalation 29
6.2.2. Oral 29
6.2.3. Other Relevant Information 30
6.3. MUTAGENICITY 32
6.4. DEVELOPMENTAL TOXICITY ' 32
6.5. OTHER REPRODUCTIVE EFFECTS 34
6.6. SUMMARY 35
7. EXISTING GUIDELINES AND STANDARDS 38
7.1. HUMAN 38
7.2. AQUATIC 38
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TABLE OF CONTENTS (cont.)
8. RISK ASSESSMENT 39
8.1. CARCINOGENICITY 39
8.1.1. Inhalation 39
8.1.2. Oral 39
8.1.3. Other Routes 39
8.1.4. Weight of Evidence 39
8.1.5. Quantitative Risk Estimates 40
8.?. SYSTEMIC TOXICITY 40
8.2.1. Inhalation Exposure 40
8.2.2. Oral Exposure 40
9. REPORTA8LE QUANTITIES 43
9.1. BASED ON SYSTEMIC TOXICITY .' 43
9.2. BASED ON CARCINOGENICITY ; 43
10. REFERENCES 45
APPENDIX A: LITERATURE SEARCHED 63
APPENDIX B: SUMMARY TABLE FOR 2-CHLOROPHENOL 66
APPENDIX C: DOSE/DURATION RESPONSE GRAPH(S) FOR EXPOSURE TO
2-CHLOROPHENOL 67
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LIST OF ABBREVIATIONS
ATP Adenoslne tMphosphate
BCF B1oconcentrat1on factor
CAS Chemical Abstract Service
CS Composite score
OMBA 9,lO-d1methy1-l,2-benzath1acene
ONA OeoxyMbonuclelc add
OWEL Drinking water exposure level
EC5Q Concentration effective to 50% of recplents
(and all other subscripted dose levels)
£050 Effective dose to 50% of recipients
ENU Ethylnltrosourea
GMAV Genus mean acute value
GMCV Genus mean chronic value
Koc Soil sorptlon coefficient
Kow Octanol/water partition coefficient
LC5Q Concentration lethal to 50% of recipients
(and all other subscripted dose levels)
1050 Dose lethal to 50% of recipients
MATC Maximum acceptable toxicant concentration
MED Minimum effective dose
LOAEL Lowest-observed-adverse-effect level
NOAEL No-observed-adverse-effect level
NOEL No-observed-effect level
PCV Packed cell volume
pKa The negative logarithm (to the base 10) of the
equilibrium constant, K, for the reaction of
chlorophenol with add
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LIST OF ABBREVIATIONS (cont.)
ppb Parts per billion
ppm Parts per million
RBC Red blood cells
RfO Reference dose
RQ Reportable quantity
RVd Dose-rating value
RVe Effect-rating value
SCE Sister-chromatld exchange
TLffl Median tolerance limit
w/v Weight per volume
x1v
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1. INTRODUCTION
1.1. STRUCTURE AND CAS NUMBER
2-Chlorophenol 1s also known as ortho-chlorophenol, 2-chloro-1-hydroxy-
benzene and 2-hydroxychlorobenzene (Chemllne, 1989; SANSS, 1989). The
structure. Chemical Abstracts Service Registry number, empirical formula and
molecular weight are as follows:
CAS number: 95-57-8
Empirical formula: C.H.C10
o b
Molecular weight: 128.56
1.2. PHYSICAL AND CHEMICAL PROPERTIES
2-Chlorophenol 1s a colorless to yellow-brown liquid with an unpleasant,
penetrating odor (Sax and Lewis, 1987). It Is soluble 1n alcohol, ether,
benzene and water (Sax and Lewis, 1987; Ueast et al., 1988). A weak add
(pKa • 8.5 at 25'C), U Is freely soluble 1n alkaline solutions (Frelter,
1981). Selected chemical and physical properties for 2-chlorophenol are as
follows:
Melting point:
Boiling point:
Density at 25'C:
Vapor pressure at 25'C:
water solubility at 25'C:
Kow:
Conversion factors at 25'C:
8.7'C
175-176'C
1.2573 g/ml
2.35 ram Hg
11,350 mg/i
2.15
1 mg/m» • 0.19 ppm
1 ppm -5.25 mg/m*
Frelter. 1981
Frelter, 1981
Ulndholz et al., 1983
Suntlo et al., 1988
Banerjee et al., 1980
Hansch and Leo, 1985
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1.3. PRODUCTION DATA
During 1977, one company manufactured and two companies Imported
2-chlorophenol In the United States. A plant operated by Monsanto Co. In
Sauget, IL, produced between 10,000 and 100,000 pounds (TSCAPP, 1989).
Current production data were not located In the available literature dted
In Appendix A.
2-Chlorophenol can be synthesized by several methods, some of which
produce either the 2-chloro or the 4-chloro Isomer selectively. The
reaction of phenol with tert-butylhypochlorlte 1s more likely to form
2-chlorophenol than 4-chlorophenol. Sodium p-phenol sulfonate, prepared
from phenol, can be chlorinated and desulfonated to give 2-chlorophenol.
Hydrolysis of 1,2-d1chlorobenzene with strong bases 1n the presence of a
catalyst produces 2-chlorophenol. Ortho-chlorocumene can be oxidized to the
corresponding peroxide and converted to 2-chlorophenol. 2-Chlorophenol Is
produced, along with numerous other chlorinated phenol Isomers, by the
direct chlorlnatlon of phenol at elevated temperatures. Purification of
this complex mixture Is one method of obtaining 2-chlorophenol (Frelter,
1981).
1.4. USE DATA
Most commercially produced 2-chlorophenol 1s used directly In the
synthesis of higher chlorinated phenols or as a chemical Intermediate In the
production of larger synthetic molecules. Approximately IX of total produc-
tion Is Isolated for use as a preservative, 1n specialized phenolic resins,
as a specialty solvent In the rubber Industry, as a polymer Intermediate In
the manufacture of f1re-retardant varnishes and as an amlnlzlng agent for
cotton fabric (Frelter, 1981; Scow et al., 1982).
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1.5. SUMMARY
2-Chlorophenol 1s a colorless to yellow-brown liquid with an unpleasant,
penetrating odor. It 1s soluble 1n alcohol, ether and water (Sax and Lewis,
1987; Ueast et al., 1988). A weak add, H Is freely soluble 1n basic
solutions (Frelter, 1981). Current production volume data were not located;
however, between 10,000 and 100,000 pounds was manufactured or Imported In
the United States In 1977 (TSCAPP, 1989). Most of the 2-chlorophenol pro-
duced 1s either used directly In the synthesis of other chlorinated phenols
or a.s an Intermediate In the production of larger synthetic molecules.
•f
Approximately IX of production Is Isolated for use 1n disinfectants, resins
and other specialty products (Frelter, 1981; Scow et al., 1982).
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2. ENVIRONMENTAL FATE AND TRANSPORT
2.1. AIR
HHh a vapor pressure at 25*C of 2.35 mm Hg (Suntlo et al., 1988),
2-chlorophenol probably exists almost entirely In the vapor phase 1n the
atmosphere (E1senr1ch et al., 1981).
2.1.1. Reaction with Hydroxyl Radicals. An estimated rate constant for
the gas-phase reaction of 2-chlorophenol with photochemically produced
hydroxyl radicals Is 1.03xlO"11 cm'/mol-sec (Atkinson, 1985). Assuming
an average atmospheric hydroxyl radical concentration of 5xl09
molecule/cm3 (Atkinson, 1985), then the half-life for this reaction Is 1.6
days. 2-Chlorophenol reacts In the dark with nitrogen oxides (Kanno and
NoJIma, 1979). The yields of 2-chloro-6-n1trophenol and
*
2-chloro-4-n1trophenol after 5 hours 1n a NO reactor were 30 and 36X,
respectively, of the original material. Thus, the nighttime gas-phase
reaction of 2-chlorophenol with nitrate radicals may be an Important fate
process In urban atmospheres.
2.1.2. Reaction with Ozone. The atmospheric reaction of 2-chlorophenol
with ozone Is not expected to be an Important fate process (Atkinson, 1985).
2.1.3. Photolysis. Sufficient data are not available to predict the
Importance of the photolysis of 2-chlorophenol 1n the atmosphere. The
un-1on1zed form undergoes photolytlc breakdown In water; however, this 1s
believed to result from stabilization of the polar zwHteMonlc transition
state by water (Boule et al., 1982, 1984. 1987). This type of stabilization
Is not possible 1n the gas phase.
2.1.4. Physical Removal Processes. Based on the water solubility of
2-chlorophenol, 11,350 mg/i at 25'C (Banerjee et al., 1980), wet deposi-
tion may be a significant fate process.
0220d -4- 11/01/89
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2.2. WATER
2.2.1. Hydrolysis. 2-Chlorophenol 1s not expected to undergo hydrolysis
In water, as 1t contains no readily hydrolyzable functional groups (Harris,
1982).
2.2.2. Oxidation. Pertinent data regarding the oxidation of 2-chloro-
phenol In water were not located 1n the available literature cited In
Appendix A.
2.2.3. Photolysis. The laboratory photolysis of 2-chlorophenol at a pH
of 9 (Ionized form) at 296 nm rapidly produced chloride 1on and cyclopenta- ;
•1
V
dlene carboxylates, the .latter dlmerlzlng under the reaction conditions. In V
the relatively dilute concentration expected In the environment, dlmerlza-
tlon of the reaction products Is not expected. Photolysis of the neutral
species (acidic pH) produced both cyclopentadlenlc adds and catechol, with
a rate of disappearance 1 order of magnitude less than that for the Ionized
form (Boule et al.. 1982, 1984, 1987).
2.2.4. M1crob1al Degradation. In a screening study, 2-chlorophenol at
concentrations of 5 and 10 mg/mi underwent 86 and 83% aerobic degradation
In 7 days using a settled domestic wastewater Inoculum. The second sub-
culture allowed complete degradation of both samples 1n the same time period
(Tabak et al., 1981). 2-Chlorophenol at a concentration of 1, 10 and 100
mg/l underwent 100. 100 and 17% degradation after 3, 3 and 6 hours,
respectively, using a sewage sludge seed under aerobic conditions. The
decrease 1n degradation at 100 mg/i Is believed to be due to the toxlclty
of the microbes to elevated concentrations of this substrate (Balrd et al.,
1974).
Domestic sewage treatment plant sludge was successfully acclimated to
2-chlorophenol within 24 days (Lund and Rodriguez, 1984). 2-Chlorophenol
underwent aerobic blodegradatlon using water from a pristine aquifer and
0220d -5- 09/18/89
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when combined with acclimated 'organisms In groundwater obtained near a
municipal waste site; degradation was complete In 9 and 6 days, respec-
tively. Using these same sources of microorganisms under anaerobic condi-
tions, degradation occurred only In aquifers that were actively methanogenlc
(Sufllta and Miller, 1985).
That the anaerobic mineralization of 2-chlorophenol requires methano-
genlc microorganisms was also demonstrated using an upflow bloreactor and an
acclimated sludge Inoculum (Krumme and Boyd, 1988). However, 2-chlorophenol
at a concentration of 50 mg C/l did not undergo anaerobic degradation
under methanogenlc conditions In a screening test using an aerobic digester
sludge (Battersby and Wilson. 1989). The failure for 2-chlorophenol to
undergo degradation may be due to a high- concentration of substrate used In
this study.
2.2.5. B1oconcentrat1on. A BCF of 214 was determined for 2-chlorophenol
using blueglll sunflsh, Lepomls macrochlrus. 1n a continual-flow system for
28 days of exposure (Barrows et al., 1980). This value suggests that bio-
concentration In fish and aquatic organisms 1s not an Important fate process.
2.2.6. Adsorption. 2-Chlorophenol was found In 8X of water samples taken
from Lake Ketekmeer 1n the Netherlands but not In sediment samples from the
lake (detection limit, 10 wg/kg) (Wegman and van den Broek, 1983).
Adsorption of phenols to sediment and suspended organic matter appears to be
a complicated process, and Its Importance can vary widely with local
conditions (Section 2.3.2.).
2.2.7. Volatilization. Based on a Henry's Law constant of 8.14xlO~»
atncmVmol at 25°C (Smith et al., 1983), an estimated volatilization
half-life for a model river 1 m deep, flowing 1 m/sec with a wind velocity
of 3 m/sec Is 5.2 days (Thomas, 1982). Volatilization from water to the
0220d -6- 09/18/89
-------
atmosphere may, therefore, be significant. Adsorption to sediment and
suspended organic matter, however, may attenuate this process.
2.3. SOIL
2.3.1. H1crob1al Degradation. The aerobic degradation of 2-chlorophenol
at an Initial concentration of 100 mg/i was complete In 3 days using an
activated soil sludge Inoculum (Ingols et al., 1966). Aerobic degradation
of 2-chlorophenol (16 mg/i) by unadapted supernatant from domestic waste-
water sludge was complete In 14-25 days. Using a soil Inoculum, aerobic
degradation did not occur In >25 days (Mailer, 1978).
2-Chlorophenol, added as a component of a complex mixture to three
undisturbed soils (ranging from clay to sandy) 1n a glass biological soil
reactor, underwent aerobic degradation, with half-lives ranging from 28-228
days (Klncannon and Lin, 1985). 2-Chlorophenol underwent complete aerobic
degradation, using two different soils. In 14 and 47 days (Alexander and
Aleem. 1961).
2-Chlorophenol was completely degraded In 3 weeks using a sewage sludge
seed under anaerobic conditions. Phenol was Identified as an early product
In this transformation; thus, the first step Is believed to be loss of the
chlorine substltuent (Boyd et al., 1983). Anaerobic degradation of
2-chlorophenol using freshwater sediment and a digester sludge Inoculum
occurred In >29 and >8 weeks, respectively (Horowitz et al.. 1982). Aerobic
degradation of 100 pg/g (wet weight) 2-chlorophenol 1n a clay soil loam
was very rapid; complete degradation was seen 1n 1.5 days. Under anaerobic
conditions with the same soil, 78% degradation occurred after 80 days (Baker
and Mayfleld, 1980). 2-Chlorophenol at an Initial concentration of 100 ppm
In a clay loam underwent 91 and 94% degradation under anaerobic conditions
at 4°C (6.5 days) and 0°C (8 days), respectively. In sediment from a small
0220d -7- 08/09/89
-------
stream. It underwent 100% degradation In 10-15 days at 20°C, and 78%
degradation In 30 days at 0°C (Baker et al.. 1980).
2.3.2. Adsorption. Experimental K values obtained In sediment from
Lake Zoar, CT, were 4890 for fine samples and 3990 for coarse samples
(Isaacson and F1nk, 1984). For phenols, subtle factors such as pH and the
organic, mineral or metal Ion content can drastically Influence the adsorp-
tion characteristics of 2-chlorophenol. The formation of hydrogen bonds
with the organic matter or the formation of complexes with metallic Ions are
probably more Important than hydrophoblc forces. 2-Chlorophenol vapors also
strongly adsorb to sediment (Isaacson, 1985). An experimental K of
51.15 was obtained on a Brookston clay loam (Boyd, 1982). Apparently, the
process of adsorption Involves several subtle factors that can vary widely
with the local conditions.
2.3.3. Volatilization. Based on the vapor pressure of 2-chlorophenol,
2.35 mm Hg at 25°C (Suntlo et al., 1988), volatilization from the soil
surface to the atmosphere may occur. However, the rate of volatilization
may be attenuated due to adsorption.
2.4. SUMMARY
In the atmosphere, 2-chlorophenol Is expected to exist almost entirely
In the vapor phase (Suntlo et al., 1988). The gas-phase reaction with
photochemically produced hydroxyl radicals 1s expected to be rapid, with an
estimated half-life of 1.6 days (Atkinson. 1985). Nighttime degradation by
the gas-phase reaction with nitrate radicals 1s expected to be significant
1n urban areas (Kanno and NoJIma, 1979). Physical removal of 2-chlorophenol
by wet precipitation may also occur. In water, photolysis and microblal
degradation are expected to be significant. In basic waters, the Ionic form
of 2-chlorophenol undergoes rapid photolysis. The neutral form photollzes
0220d -8- 08/09/89
-------
more slowly (Boule et al., 1982. 1984, 1987). H1crob1al degradation under
aerobic (Tabak et al., 1981; Balrd et al., 1974; Lund and Rodriguez, 1984;
SuflUa and Miller, 1985) and anaerobic (Krumme and Boyd, 1988; Battersby
and Wilson, 1989; Sufi Ha and Miller, 1985) conditions has been demon-
strated. Bloconcentratlon In aquatic organisms Is not expected to be
significant. Volatilization from water to the atmosphere Is expected; how-
ever, this process may be attenuated by adsorption to sediment and suspended
matter. In soil, blodegradatlon Is expected to be the dominant fate
process. Mlcroblal degradation using a soil Inoculum has been demonstrated
under aerobic (Alexander and Aleem, 1961; Ingols et al., 1966; Haller, 1978;
Klncannon and Lin, 1985) and anaerobic (Boyd et al., 1983; Horowitz et al..
1982) conditions. Volatilization from the soil surface to. the atmosphere 1s
expected; however. It may be attenuated by the process of adsorption.
0220d -9- 08/09/89
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3. EXPOSURE
2-Chlorophenol can enter the environment as a fugitive emission from
commercial plants that synthesize or use this compound. It can also enter
the environment as a product of the chemical or biological degradation of
other anthropogenic compounds.
An estimated 934 workers are potentially exposed to 2-chlorophenol
(NIOSH, 1984). Occupational exposure may occur by Inhalation or dermal
contact during the production, purification and formulation of 2-chloro-
phenol. Sufficient data are not available to predict exposure to the
general population.
3.1. WATER
2-Chlorophenol has been qualitatively Identified 1n drinking water In
the United States (Kool et al.. 1982; Lucas. 1984) and In 1/10 effluent
samples from Industrial and publicly owned treatment plants In Illinois
(Ellis et al., 1982). 2-Chlorophenol was found at a concentration of <10
wg/l In primary effluent from publicly owned treatment plants 1n Los
Angeles, San Diego and Orange County, CA (Young, 1978). 2-Chlorophenol was
found In 2% of 48 source samples, taken to determine possible routes of
contamination to the Influent of two sewage treatment plants, at an average
concentration of 15 ppb (Callahan et al., 1979). It was Identified as a
constituent of chlorinated municipal sewage effluent at a concentration of 2
ppb (Bourquln and Gibson, 1978). 2-Chlorophenol was not detected 1n raw
water samples obtained at drinking water treatment plants In six Canadian
cities and was found 1n one of six samples of treated water at a
concentration of 39 ng/i (SUhole et al., 1986). It was also found In IX
of 86 samples taken from 19 dtles during the Nationwide Urban Runoff
0220d -10- 09/18/89
-------
Program at a concentration of 2 yg/l (Cole et al., 1984). In the
Netherlands, U was found at concentrations <21 yg/l In the effluent of
the following Industries, none of which produced 2-chlorophenol: herbicides,
organic dyes and agrochemlcals (Berbee, 1986). It Is a known component of
pulp mill effluent (Suntlo et al., 1988).
2-Chlorophenol was found In groundwater samples obtained near a chemical
manufacturing plant 1n Australia (Stepan et al., 1981). It was found In 2X
of 1976 samples taken In 1976 from the Rhine River 1n the Netherlands at a
maximum concentration of 2.3 yg/l; U was not found In any samples taken
from the same river In 1987 (Wegman and Hoestee, 1979).
3.2. FOOD
Pertinent data regarding exposure.to 2-chlorophenol through food were
not located In the available literature cited In Appendix A.
3.3. INHALATION
Data on the atmospheric concentration of 2-chlorophenol are lacking. It
was Identified In effluent from waste Incinerators In three of five samples
at concentrations ranging from 6.9-13 yg/mi (James et al.. 1984).
3.4. DERMAL
Pertinent data regarding dermal exposure to 2-chlorophenol were not
located 1n the available literature dted In Appendix A.
3.5. OTHER
2-Chlorophenol may be formed In the atmosphere by the sequential, photo-
Initiated degradation of chlorobenzene or 2-n1trochlorobenzene (Kanno and
NoJIma, 1979). It can also be formed by the chlorlnatlon of phenol In the
disinfection of drinking water (Carlson and Caples, 1975; Joshlpura and
Kellher, 1980). It Is formed In water by the photo1nU1ated hydrolysis of
l,4-d1chlorobenzene (Boule et al., 1985). Thermolysis of two different
0220d -11- 09/18/89
-------
vinyl1dene chloride polymers at 200-600'C produced an average of 13.5 and
11.3 yg of 2-chlorophenol/g of polymer (Yasuhara and Morlta, 1988).
3.6. SUMMARY
2-Chlorophenol can enter the environment as a result of Us commercial
synthesis or use. 2-Chlorophenol may be released to the environment through
Us formation by chemical transformations on other anthropogenic compounds
(Kanno and NoJIma, 1979; Carlson and Caples, 1975; Joshlpura and Kellher,
1980; Boule et al., 1985; Yasuhara and Morlta, 1988).
Data on the occurrence of 2-chlorophfcnol 1n?the environment are lacking.
•:!f
The compound has been qualitatively Identified In drinking water In the
United States (Kool et al.. 1982; Lucas, 1984) and quantified 1n effluents
from publicly owned treatment plants (Ellis et al., 1982; Young, 1978;
Callahan et al., 1979; Bourquln and Gibson, 1978).
0220d -12- 09/18/89
-------
4. ENVIRONMENTAL TOXICOLOGY
4.1. AQUATIC TOXICOLOGY
4.1.1. Acute Toxic Effects on Fauna. Many studies regarding the acute
toxldty of 2-chlorophenol to cladoceran Invertebrates have been done.
Studies on daphnlds Included mostly static 48-hour tests conducted In
18-22'C water with Daphnla magna that were <24 hours old. The 48-hour
EC50 values reported for Immobilization of Daphnla varied from 2.6-7.43
mg/l In these tests. Details of the Individual studies are presented In
Table 4-1.
The toxldty of 2-chlorophenol has been examined In two species of salt-
water Invertebrates: the shrimp, Cranqon septemsplnosa. and the soft-shelled
clam, Hya arenaMa (HcLeese et al., 1979). Three members of each species
were exposed simultaneously to each concentration for 96 hours at 10*C. A
lethal threshold was determined based on the time to SOX mortality at each
chemical concentration. The 96-hour lethal threshold (geometric mean of
highest concentration with no mortality and next highest concentration with
100X mortality) In shrimp was 5.3 mg/l. The data were Insufficient to
generate a lethal threshold for clams.
Pickering and Henderson (1966) performed acute toxldty tests on a
series of freshwater fish, Including bluegllls, Lepomls macrochlrus. fathead
minnows, Plmephales promelas, goldfish, Carasslus auratus. and gupples,
PoedHa retlculata. Ten of each spedes (two groups of five) were exposed
to nominal concentrations of 2-chlorophenol under static conditions 1n soft
water (pH«7.5; alkalinity-IB mg/l; hardness-20 mg/l) at 25°C. Toxldty
was similar In three of these species, with 96-hour LC5Q values of 10.00
mg/l In bluegllls, 11.63 mg/l 1n fathead minnows, and 12.37 mg/l In
goldfish. Gupples, which were slightly less susceptible to 2-chlorophenol,
0220d -13- 09/18/89
-------
0
ro
r\j
o
ex
1
^^
1
Acute loxtclty Studies
Species Age lest experimental Design
lype
Oaphnla magna <24 hours static >S nonlnal concentrations
3 replicates/concentration
n • S/repltcate
0. magna <24 hours static 2 replicates/concentration
0. magna <24 hours static 2 tests
0. reagna >24 hours static >3 tests
4 concentrations/test
4 replicates/concentration
n - S/repllcate
0. magna NR Nfi 3 tests
0. magna NR ' NR NR
0. magna <72 hours static 3 tests
4 replicates/concentration
n • 5/repllcate
0. aagna NR NR NR
Daphnla pulen <24 hours static 10 replicates/concentration
n * 2/repltcate
1ABK 4-1
In Qaphnla
Using 2-Chlorophenot
Icnperature Ourat lon/tndpolnt
CC)
22
18
22
IB
NR
20
20
NR
20
24 -hour lC$o
46-hour tC«,o
48 hour IC0
48 -hour 1C 1,0
(liwobl Miatton)
48 -hour ECso
(tmoblltialton)
48 hour tC^o
24 -hour (€50
(lonobl Itiatton)
24 -hour lC«,o
(lowobl 11 ration)
24 -hour tC^o
(Innobtlt/alton)
"50
fC0
tc)00
96 -hour IC^Q
Concentration
>22 »g/l
2.6 (2.1 3.2)«g/t
1.0 MJ/I
3.91(3.31-4.91) *g/l
6.20 rog/l
7.43 ng/t
8 ng/1
11.7 ng/i
17.95 (16.6-19.3) *g/t
23 mg/l
10 mg/t
64 rog/l
6.9 mg/l
Reference
LeBlanc. I960
Keen and
Balllod. 1985
Randall and
Knopp. 1980
Koppernan
et al.. 1974
Baitn et al.,
1987
llssot
et al.. 1985
Devi Hers and
Chambon. 1986
Knle et al.,
1983
Irabalka and
Burch. 1978
o
00
NR -- Not reported
CD
CD
-------
had a 96-hour LC5Q of 20.17 mg/i. In a second assay, performed only
with fathead minnows, a hard dilution water was used with higher pH (8.2),
alkalinity (300 mg/i) and hardness (360 mg/l) than the soft water; the
96-hour LC-g 1n hard water (14.48 mg/i) was not significantly different
from that obtained using soft water (11.63 mg/l). This Indicates that
these water quality variables did not affect the toxldty of 2-chlorophenol
In this study. The 24-hour KL. values for blueglll, goldfish and gupples
were slightly higher than the 96-hour values for these species, Indicating
that most deaths occurred early In the study. Only In fathead minnows was
the 96-hour LC5Q (11.63 mg/l) significantly lower than the 24-hour value
(21.96 mg/l), suggesting the occurrence of significant mortality during
the second and third days of the study.
Acute toxldty studies by other authors have generally reported similar
results. Buccafusco et al. (1981) examined the acute toxldty of 2-chloro-
phenol 1n blueglll, L. macrochlrus. One group of 10 fish was exposed to
each nominal concentration under static conditions at 22°C. The 24- and
96-hour LCcQ values were 7.2 and 6.6 mg/l, respectively. Lammerlng and
Burbank (1961), also working on blueglll, L. macrochlrus. reported 24- and
48-hour LCgo values of 8.2 and 8.1 mg/l, respectively, based on static
tests (water renewed after 24 hours) conducted on groups of 10 fish per
concentration at 20*C. Phlpps et al. (1981) performed both static and
flowthrough tests of the toxldty of 2-chlorophenol to fathead minnows, P.
promelas. In the static test, fish were exposed 1n groups of 20 to
different concentrations of the chemical at 21.6-25.4*C. The 48-hour LC5Q
was 9.7 mg/l. In the flowthrough tests, 100 fish (two groups of 50) were
exposed to each measured concentration at 25'C. The 96- and 192-hour LCrQ
values were 12 and 6.3 mg/l, respectively. Kobayashl et al. (1979)
0220d -15- 09/18/89
-------
reported a 24-hour LC5Q of 16 ppm (mg/i) In goldfish, Carasslus auratus.
In a static renewal test conducted at 20°C using 10 fish at each exposure
concentration. Konemann and Husch (1981) conducted static acute toxldty
tests on gupples, Poecllla retlculata. Eight fish were tested at each
concentration; the tests were conducted at 22°C for 7-14 days. The LC5fl
decreased from 13.46 mg/i at pH 7.8-11.2 mg/i at pH 7.3 and 7.06 mg/i
at pH 6.1, suggesting that the toxldty of 2-chlorophenol was Influenced by
pH In this study. In a screening-type study conducted on two members of
three different fish species, Applegate et al. (1957) found that 24-hour
static exposure to a nominal concentration, of 5 ppm (mg/i) of 2-chloro-
phenol at 13°C had no effect on bluegllls or larval sea lampreys, Petromyzon
marlnus. 2-Chlorophenol at this exposure concentration produced death In
rainbow trout, Salmo qalrdnerll. after 13 hours.
4.1.2. Chronic Effects on Fauna.
4.1.2.1. TOXICITY —An early life stage toxldty test was conducted
on fathead minnows, £. promelas. by LeBlanc (1983). The eggs (and larvae
after hatching) were exposed under flowthrough conditions to mean measured
concentrations of 0.78, 1.1, 1.7, 2.6 and 4.0 mg/i of 2-chlorophenol.
Untreated and solvent controls were also Included. Endpolnts examined were
percent hatch of eggs and percent survival, length and weight of larvae at
30 days post-hatch. No effects were reported at any concentration.
4.1.2.2. BIOACCUHJLATION/8IOCONCENTRATION — The tendency of
2-chlorophenol to bloconcentrate In fish was studied by Barrows et al.
(1980). A total of 100 blueglll sunflsh, L.. macrochlrus. were exposed to a
mean measured concentration of 9.2 yg/i of radlolabeled 2-chlorophenol
for 28 days under flowthrough conditions. A 7-day depuration period
followed. The equilibrium BCF measured at 28 days was 214. The half-life
Q220d -16- 08/09/89
-------
for elimination of 2-chloropheno! from the tissues was <1 day. The rela-
tively low BCF and short biological half-life Indicate that this compound Is
not concentrated or retained significantly by blueglll.
4.1.3. Effects on Flora.
4.1.3.1. TOXICITY — Two studies have Investigated the toxldty of
2-chlorophenol to aquatic plants. Static 96-hour assays were conducted by
Shlgeoka et al. (1988) on two species of green algae, Selenastrum capricorn-
11 turn and Chlorella vulqaMs. Test algae were exposed to five nominal con-
centrations of 2-chlorophenol at 21°C. The EC5Q values for growth inhibi-
tion, calculated from measurements of cell density, were 70 ppm (mg/i) for
S. capricornutum and 170 ppm (mg/i) for C_. vulgaris. 2-Chlorophenol did
not affect chlorophyll concentration or oxygen production in the green alga,
Chlorella pyrenoidosa. at concentrations of <10 mg/i, but oxygen produc-
tion was reduced to 88% of control at 100 mg/i and to 74% of control at
500 mg/i (Huang and Gloyna. 1968). In this study, algal cultures were
exposed to nominal concentrations of the test chemical for 72 hours under
static conditions at 25°C.
4.1.3.2. BIOCONCENTRATION — Pertinent data regarding the bioconcen-
tration potential of 2-chlorophenol in aquatic flora were not located in the
available literature cited in Appendix A.
4.1.4. Effects on Bacteria. The effects of 2-chlorophenol on bacteria
have been studied in several different ways. The most common assay that has
been done Is the Hlcrotox test on Photobacterium phosphoreum. which measures
the reduction in light emitted from this photolumlnescent species following
exposure to a chemical. EC5Q values reported by various authors range
from 14.7-40 mg/l for tests lasting 5-30 minutes (Bazin et al., 1987;
Cunningham et al., 1986; Curtis et al., 1982; Ribo and Kaiser, 1983). A
0220d -17- 08/09/89
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second assay Involved quantifying nitrification activity by Nltrobacter
(Wang and Reed, 1984). Nitrite utilization was reduced 25-27% following
4-hour exposure to 50 mg/l of 2-chlorophenol. Another study examined the
effect of 2-chlorophenol exposure on ATP content 1n both the heterotrophk
bacteria, Escherlchla coll. and the nitrifying bacteria, NUrosomonas
eurooaea (Parker and Prlbyl, 1984). The effect was greater on N. europaea;
following 20-m1nute exposure, the percent reduction 1n ATP Increased from
24-32% as the concentration of 2-chlorophenol Increased from 100-400 mg/i.
The percent reduction In ATP content of E_. coll Increased from 6.5-23% as
the exposure concentration Increased from 100-1000 mg/t. One study
evaluated the ability of 2-chlorophenol to Inhibit bacterial dehydrogenase
activity 1n a mixed bacterial culture (Liu et al., 1982). The EC-0 for
this effect was 700 mg/i.
4.2. TERRESTRIAL TOXICOLOGY
4.2.1. Effects on Fauna. Only one study regarding the effects of
exposure of terrestrial fauna to 2-chlorophenol was located In the available
literature. Red-winged blackbirds trapped 1n the wild and held 1n captivity
for 2-6 before testing were given single doses of 2-chlorophenol by gavage
1n propylene glycol (Schafer et al., 1983). The estimated L05Q for
2-chlorophenol In red-winged blackbirds was >113 rag/kg.
4.2.2. Effects on Flora. Pertinent data regarding the effects of
exposure of terrestrial flora to 2-chlorophenol were not located 1n the
available literature dted In Appendix A.
4.3. FIELD STUDIES
Pertinent data regarding the effects of 2-chlorophenol on flora and
fauna In the field were not located 1n the available literature dted In
Appendix A.
0220d -18- 09/18/89
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4.4. AQUATIC RISK ASSESSMENT
The lack of pertinent data regarding the effects of exposure of aquatic
fauna and flora to 2-chlorophenol prevented the development of a freshwater
criterion by the method of U.S. EPA/OURS (1986). Available data are
displayed In Figure 4-1. Additional data required for the development of a
freshwater criterion Include the results of acute assays with a salmonld
fish species, a benthlc crustacean, an Insect, a nonarthropod and non-
chordate species and an Insect or species from a phylum not previously
represented. The development of a freshwater criterion will also require
data from an additional chronic toxldty test on either a fish or an
Invertebrate.
Pertinent data regarding the effects .of exposure of marine fauna and
flora to 2-chlorophenol were not located In the available literature. Acute
studies with representatives from eight families of marine fauna and at
least three chronic studies and one bloconcentratlon study with marine fauna
and flora are needed to develop a saltwater criterion.
4.5. SUMMARY
The acute toxldty of 2-chlorophenol was similar In all species of
freshwater fish examined, with LCrQ values ranging from 6.6-10.0 mg/i In
the blueglll, L. macrochlrus (Buccafusco et al., 1981; Lammerlng and
Burbank, 1961; Pickering and Henderson, 1966), 9.7-14.48 mg/i In the
fathead minnow, P_. proroelas (Phlpps et al., 1981; Pickering and Henderson,
1966), 12.37-16 mg/i In the goldfish, C. auratus (Kobayashl et al., 1979;
Pickering and Henderson, 1966), and 7.06-20.17 mg/i 1n the guppy, P.
retlculata (Konemann and Musch, 1981; Pickering and Henderson, 1966). In a
screening-type study, 5 mg/l had no effect on blueglll or sea lamprey. P..
marlnus. but produced death In trout, S. ga1rdner11. within 13 hours
0220d -19- 08/09/89
-------
TEST TYPE
Family
#1
Chordate (Salmonid-fish)
#2
Chordate (warmwater fish)
#3
Chordate (fish or amphibian)
14
Crustacean (planktonic)
#5
Crustacean (benthic)
#6
Insectan
#7
non-Arthropod/ -Chordate
18
New Insectan or phylum
representative
#9
Algae
#10
Vascular plant
GMAVa
(mg/L)
NA
8.1*
12*
4.6'
NA
NA
NA
NA
NA
NA
GMCVa
(mg/L)
NA
NA
*4«
NA
NA
NA
NA
NA
709
NA
BCFa
NA
214C
NA
NA
NA
NA
NA
NA
NA
NA
•NA.Not Available
"Acute value for blueglll sunflsh, Leoomis macrochlrus
CBCF for blueglll sunflsh
'LCio for fathead minnow, Plmeohales promelas
•Chronic value for fatnead minnow
'Acute value for Daphnia maqna
9EC>0 for growth Inhibition in Selenastrum caoricornutum
FIGURE 4-1
Organization Chart for Listing GMAVs, GMCVs, and BCFs Required to Derive
Numerical Hater Quality Criteria by the Method of U.S. EPA/OHRS (1986) for
the Protection of Freshwater Aquatic Life from Exposure to 2-Chlorophenol
0220d -20- 08/09/89
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(Applegate et al., 1957). Exposure to concentrations <4 mg/l for 30 days
had no effect on eggs and larvae of fathead minnows In an early life stage
toxldty test (LeBlanc, 1983). The BCF determined In blueglll was 214; the
elimination half.life was <1 day (Barrows et al., 1980). Studies using
freshwater Invertebrates revealed that toxic effects occurred at concentra-
tions similar to those found for fish. LC5Q and Immobilization EC5Q
values In Daphnla ranged from 2.6-23 mg/l (Bazln et al., 1987; Devlllers
and Chambon, 1986; Keen and Balllod, 1985; Kn1e et al., 1983; Kopperman et
al.. 1974; LeBlanc, 1980; Randall and Knopp, 1980; Tlssot et al., 1985;
Trabalka and Burch, 1978). The lethal threshold was 5.3 mg/l In the
shrimp, C. septemsplnosa. the only saltwater animal studied. Among
freshwater algae. EC5Q values for growth Inhibition were 70 mg/l In S.
caprlcornutum. and 170 mg/l 1n C. vulgarls (Shlgeoka et al., 1988).
Effects 1n bacteria Included 50% reduction 1n light emitted by P. phospho-
reum at 14.7-40 mg/l (Bazln et al., 1987; Cunningham et al., 1986; Curtis
et al., 1982; Rlbo and Kaiser, 1983), 25-27% reduction 1n nitrite utiliza-
tion by Nltrobacter at 50 mg/l (Wang and Reed, 1984), decreased ATP
content In E_. coll and N. europa at 100-1000 mg/l (Parker and Prlbyl,
1984) and 50% reduction In bacterial dehydrogenase activity In a mixed
bacterial culture at 700 mg/l. Among terrestrial organisms, the oral
LDr 1n red-winged blackbirds was >113 mg/kg (Schafer et al., 1983).
0220d -21- 09/18/89
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5. PHARNACOKINETICS
5.1. ABSORPTION
Delchmann and Kepllnger (1981) reported that the chlorophenols (not
specifically 2-chlorophenol) are absorbed readily from the gastrointestinal
tract and from sites of parenteral Injection. Carpenter et al. (1985)
reported that peak plasma levels of radioactivity were reached 2 hours after
male rats were treated by gavage with 50 mg/kg 14C-labeled 2-chlorophenol
In corn oil (plasma levels not reported). At 24 hours after treatment,
urinary radioactivity accounted for 91% of the administered dose. Only 4X
of the dose was recovered In the feces by 24 hours. Spencer and Hill lams
(1950) administered 2-chlorophenol emulsified with water to chinchilla
rabbits (gender not specified) and reported that 101.IX of the dose was
accounted for as urinary metabolites. The duration of the urine collection
period was not reported. Considered together, these data Indicate that
absorption of 2-chlorophenol from the gastrointestinal tract 1s rapid and
virtually complete.
Roberts et al. (1977) performed an Vn vitro study of the permeability of
human epidermis to various concentrations of phenolic compounds. A 2.5
cm2 portion of the epidermal layer of abdominal skin obtained at autopsy
was supported In a diffusion cell and exposed to reagent grade 2-chloro-
phenol In water. 2-Chlorophenol was absorbed by the epidermal membrane,
with a permeability coefficient of 5.5lxlO~Vcm/m1nute and a threshold
concentration for tissue damage of 0.8% (w/v).
Permeation of 2-chlorophenol 1n saline through Intact and denuded skin
of hairless SKH-hr-1 mice (60-100 days old) was studied by Huq et al. (1986)
using ]£ vitro diffusion cell methods. The permeability coefficients for
2-chlorophenol at concentrations of 0.05, 0.19 and 0.50 g/100 mi through
0220d -22- 09/18/89
-------
whole skin were 107x10"*, 116x10"' and 140xlO~Vcm/hour, with an
average lag times of 21.9, 10.3 and 6.3 minutes, respectively. The
permeability coefficients of 2-chlorophenol In approximately the same
concentrations through skin stripped of the stratum corneum were 253xlO"3,
276xlO'3 and 214xlO"Vcm/hour, with lag times of 11.5, 5.5 and 8.5,
respectively.
5.2. DISTRIBUTION
Liver and kidney tissues from weanling female Sprague-Oawley rats given
drinking water containing 2-chlorophenol (97% pure) for 10 weeks, continuing
through breeding, gestation and 3 weeks postparturltlon were analyzed for
2-chlorophenol content (Exon and Holler, 1982). Following exposure to 0, 5,
50 and 500 ppm, respectively, the levels In livers (from three pooled
' •
samples/group) were 0.16, 2.20, 3.20 and 0.08 ppm; the levels In the kidney
(pooled tissues from five rats/group) were 0.26, 2.60, 2.40 and 2.00 ppm.
The lower levels In the tissues of rats given higher doses were not
explained.
Significant amounts of radioactivity were found In the gastrointestinal
tracts and the fat of male rats treated by gavage with 14C-labeled
2-chlorophenol In corn oil at 50 mg/kg, but levels In fat decreased
markedly by 4 hours after treatment (Carpenter et al., 1985). The compound
was rapidly excreted 1n the urine and the feces, with little distribution to
other (unspecified) tissues.
Radioactivity from radlolabeled 2-chlorophenol (probably orally admin-
istered, label not specified, dose not reported) bound to the livers and
kidneys of Gunn rats >3-4 times In Sprague-Oawley rats (Houser, 1983).
0220d -23- 09/18/89
-------
5.3. METABOLISM
Following oral administration of 2-chlorophenol at 225 mg/kg to male
Sprague-Oawley rats, the compound was recovered In the free form 1n the
urine, along with the glucuronlde and glucuronlde and sulfate conjugates of
2-ch1orohydroqu1none (Houser, 1983). After pretreatment of the rats with
B-naphthoflavone or Arochlor 1254, the proportion of metabolites recovered
as 2-chlorohydroqu1none derivatives Increased (percent of dose not
reported). In Gunn rats, oral administration of 300 mg/kg of 2-chlorophenol
resulted In 24-hour recovery of the compound In the free form, as the
glucuronlde and sulfate and as the sulfate conjugate of 2-chlorohydroqulnone
(percent of dose not reported), In the urine (Houser, 1983). 2-Chlorohydro-
qulnone derivatives were formed 8-9 times more 1n Gunn rats than .In Sprague-
Oawley rats.
In male rats treated by gavage with 50 mg/kg of 14C-labeled 2-chloro-
phenol In corn oil, 91% of the dose of radioactivity was recovered In the
urine, with a small amount appearing In the feces (Carpenter et al.. 1985).
More than 90% of the urinary radioactivity was Identified as glucuronlde and
sulfate conjugates of chlorophenol, with <2% recovered as parent compound.
In chinchilla rabbits (sex not reported) given 171.3 mg/kg of 2-chloro-
phenol emulsified with water by stomach tube (Spencer and Williams, 1950),
82.4% of the dose consisted of glucuronldes, and 18.7% consisted of ethereal
sulphates of 2-chlorophenol. No mercaptuMc add was formed. Collectively,
these data Indicate that 2-chlorophenol Is rapidly and extensively
metabolized.
5.4. EXCRETION
The most meaningful excretion data were provided by Carpenter et al.
(1985), who reported that rats treated by gavage with 50 mg/kg 14C-labeled
0220d -24- 08/09/89
-------
2-chlorophenol excreted 91X of the dose of radioactivity In the urine and 4%
In the feces within 24 hours after dosing (Carpenter et al., 1985). In
chinchilla rabbits treated with 171.3 mg/kg of 2-chlorophenol by stomach
tube, 101.IX of the dose was recovered as metabolites In the urine (Spencer
and Williams, 1950). The duration of the urine collection period was not
specified.
5.5. SUMMARY
Chlorophenols (as a class) are readily absorbed from the
gastrointestinal tract and from parenteral sites of Injection (Delchmann and
KepHnger, 1981). Orally administered 2'rChlorophenol appears to be rapidly
and almost completely absorbed from the gastrointestinal tracts of rats
(Carpenter et al., 1985; Houser, 1983) and chinchilla rabbits (Spencer and
Williams, 1950). In j_n vitro studies using human autopsy skin,
2-chlorophenol was absorbed by the epidermal membrane with a permeability
coefficient of 5.51xlO~Vcm/m1n (Roberts et al., 1977).
Following oral administration of 2-chlorophenol to rats, the compound
was found In the liver and kidney (Exon and Koller, 1982), but metabolism
and excretion occurred so rapidly that there was little distribution to body
tissues (Carpenter et al., 1985). Urinary excretion accounted for 91X of an
oral dose In rats within 24 hours of treatment (Carpenter et al., 1985).
Over 90% of the urinary excretion consisted of glucuronlde and sulfate
conjugates of the parent compound, and <2% consisted of unchanged parent
compound (Carpenter et al., 1985). Other metabolites Identified 1n the
urine of treated rats Include glucuronlde and sulfate conjugates of
2-chlorohydroqulnone (Houser, 1983), an oxidation product of 2-chlorophenol.
Glucuronlde and ethereal suflate conjugates of 2-chlorophenol In the urine
of orally treated chinchilla rabbits accounted for virtually 100X of an oral
dose (Spencer and Williams, 1950).
0220d -25- 11/01/89
-------
6. EFFECTS
6.1. SYSTEMIC TOXICITY
6.1.1. Inhalation Exposure.
6.1.1.1. SUBCHRONIC ~ Pertinent data regarding toxlclty from
subchronlc Inhalation exposure to 2-chloropheno! were not located 1n the
available literature dted In Appendix A.
6.1.1.2. CHRONIC — Pertinent data regarding toxlclty from chronic
Inhalation exposure to 2-chlorophenol were not located In the available
literature dted In Appendix A.
6.1.2. Oral Exposure.
6.1.2.1. SUBCHRONIC — In a 3-week oral toxlclty study, rats (number,
strain and sex not given In translation) were given 65 or 130 mg/kg of
2-chlorophenol 1n olive oil. At both treatment levels, weight gain was
significantly reduced, and liver weights were Increased when compared with
controls. By the third week, there were significant depressions 1n hemo-
globin levels and hematocrlt values. Hlstologlcal examinations revealed
degenerated liver tissue with congestion, atrophy, swelling, vacuollzatlon,
dilation of rough endoplasmlc retlculum and mltrochondrlal swelling and
destruction of mitochondria! cMstae (Chung, 1978).
6.1.2.2. CHRONIC — As part of a cancer study (Sections 6.2.2. and
6.2.3.), Exon and Koller (1983b, 1985) exposed groups of 24-32 male and
24-28 female Sprague-Oawley rats to 2-chlorophenol (97X pure) 1n the drink-
Ing water at levels of 0, 5, 50 and 500 ppm from weaning to -2 years of age.
The dams (groups of 12-20) of these rats had been given the same treatments
from 3 weeks of age through breeding (to untreated males) until weaning of
their progeny. During gestation days 14-21, dams also received 0.318%
0220d -26- 09/18/89
-------
ethylurea In the diet and 1 ppm nitrite (precursors of the carcinogen
ethylnltrosourea) In the drinking water. A negative control group (not
exposed to any compounds) received normal food and water; a positive control
group was administered just ENU precursors. Rats were checked dally for
morbidity; moribund or tumor-bearing animals were sacrificed, and all
tissues were examined grossly and microscopically. Body weights were
recorded monthly for all rats, and hematologlcal parameters were measured
every 2 months or every 2 weeks (Exon and Koller, 1983b) on randomly
selected animals (five males, five females) from each group.
At 7 months, mean body weights of female 'rats In most .treated groups
were significantly lower than those of controls, and the mean body weights
of male rats were generally significantly higher than those of controls, but
these data were not consistent or dose-related. At 24 months, Exon and
Koller (1985) reported that treatment with 2-chlorophenol significantly
elevated RBC. PCV and blood hemoglobin concentrations In both sexes of rats
In the 500 ppm group. Noncancer hlstopathologlc observations were not
reported.
6.1.3. Other Relevant Information. All chlorophenols reportedly Irritate
the skin and eyes, and the dusts Irritate the respiratory tract (Frelter,
1981). In humans, 2-chlorophenol Is reportedly highly toxic, causing severe
burns, some liver and kidney damage, narcosis and respiratory depression
(Davis et al., 1959).
Houser (1983) reported that a single oral administration of 300 mg/kg of
2-chlorophenol to Gunn rats (sex not reported) resulted In centrllobular
hepatic necrosis In 50% of the animals and renal necrosis In 75X of the
animals. A dose of 225 mg/kg In male Sprague-Oawley rats was not renal- or
hepatotoxlc.
0220d -27- 09/18/89
-------
Oelchmann (1943) reported L050s in rats (strain and sex not specified)
of 670 mg/kg from an orally administered dose and 950 mg/kg from a subcuta-
neous dose. Oral LOgQ values of 670 mg/kg for the mouse (strain and sex
not specified) and 440 mg/kg for the blue fox were reported (Bubnov et al.,
1969).
The acute oral LD5Qs, administered by gavage (98% pure, In deIonized
water), In 6-week-old male and female CD-I ICR mice were 347 and 345 mg/kg,
respectively (Borzelleca et al., 1985). Signs of toxkUy Included rapid
respiration, tremors and convulsions leading .to central nervous system
depression. In other studies, Borzelleca (1983) found the ED., for motor
Impairment In CD-I mice to be 63 mg/kg; maximum effect occurred 5 minutes
after treatment and was reversible. The lowest dose that produced a
behavioral change In the mice was 1 mg/kg, which resulted In a change 1n
operant behavior after 2 days of treatment.
In a 14-day behavioral toxldty study, mice (strain and sex not speci-
fied) were gavaged with 2-chlorophenol In doses of 35, 69 and 175 mg/kg/day
and compared to an untreated control group. There was 80% mortality In the
group treated with 175 mg/kg/day; mortality 1n the control group was not
reported. The 175 mg/kg/day group also showed a significant decrease In
body weight before death. HyperactlvHy was seen In the mice treated with
35 and 69 mg/kg from the fourth day of exposure until treatment was stopped
(Kailman et al., 1982).
Farquharson et al. (1958) studied the toxldty of IntraperHoneally
administered 2-chlorophenol In fasted male albino rats. The median lethal
dose of 230 mg/kg, Injected In 10 mt of olive oil/kg body weight, caused
excited behavior, running or vigorous nose-rubbing, followed wUhln minutes
0220d -28- 09/18/89
-------
by tremors and convulsions. Rats that recovered remained sluggish and hypo-
tonic for hours. The dose also produced a 2°C decrease 1n rectal
temperature when compared with controls.
IntrapeMtoneally administered 2-chlorophenol (dissolved 1n 0.9% saline)
produced clonlc convulsions In 50% of anesthetized male Sheffield albino
mice given 0.77 ymols/kg (-100 mg/kg).
Subcutaneous LD5Qs of 800 and 950 mg/kg were reported for guinea pigs
and rabbits (strain and sex not reported), respectively (ChMstensen and
Luglnbyhl, 1975).
6.2. CARCIN06ENICITY
6.2.1. Inhalation. Pertinent data regarding the carclnogenldty from
Inhalation exposure to 2-chlorophenol were not located 1n the available
literature cited 1n Appendix A.
6.2.2. Oral. In a study of the carc**gen1c-cocardnogen1c potential of
2-chlorophenol. Exon and Koller (19S3b. 1985) exposed groups of 24-32 male
and 24-28 female Sprague-Oawley rats pre-. post- or pre- and postnatally to
the compound mixed In the drinking water In concentrations of 0, 5. 50 and
500 ppm, along with prenatal exposure to ENU. ENU, a known carcinogen, was
administered as the precursors; 0.316% ethyl urea In food and 1 ppm sodium
nitrite In drinking water. In addition, a group of rats was exposed
pre- and postnatally to 2-chlorophenol without prenatal exposure to ENU; a
positive control group was treated with ENU alone.
Prenatal exposure to 2-chlorophenol consisted of exposing the dams to
the levels 1n drinking water described above from weaning through mating at
90 days of age and through weaning to postpartum day 21. Postnatal exposure
to 2-chlorophenol consisted of exposing the test animals to the levels 1n
drinking water described above at weaning for 24 months. ENU was also
0220d -29- 09/18/89
-------
administered as above, with 3.18% ethylurea In the diet given concurrently
with 1 ppm nitrite In the drinking water.
In the group prenatally exposed, the 2-chlorophenol did not produce
consistent effects In survival to weaning. According to the authors, the
weaning weight of males and females given 2-chlorophenol was generally
decreased 1n comparison with controls, but the observation was not dose-
dependent. Body weights of females remained decreased through 7 months,
whereas male rats had generally Increased body weights (p<.l). These
differences were not observed after 24 months (Exon and Koller, 1985).
2-Chlorophenol alone did not Increase the Incidence of tumors, or
decrease the t1me-to-tumor after <24 months of exposure 1n comparison with
controls. Alternatively, male offspring of rats treated with ENU and
2-chlorophenol at all treatment levels, both pre- and postnatally, had
significantly Increased Incidence of tumors when compared with the group
given only ENU. Male progeny of rats treated with ENU and 2-chlorophenol
given prenatally at 5 and 500 ppm (but not 50 ppm). and with ENU and
2-chloro- phenol given postnatally at 5 ppm, had significantly higher
Incidence of tumors compared with the ENU-treated group. Tumor Incidence
appeared to be higher In the lower dose groups, and females seemed to be
less sensitive to ENU-lnduced tumors. Tumor latency was significantly
decreased in rats exposed to ENU with both pre- and postnatal exposure to
2-chlorophenol at all treatment levels when compared with the ENU-only
group. The Investigators suggested that 2-chlprophenol may have enhanced
the cardnogenlcHy of ENU (Table 6-1).
6.2.3. Other Relevant Information. Boutwell and Bosch (1959) conducted a
study of the tumor-promoting ability of 2-chlorophenol applied dermally to
2- to 3-month-old female albino Sutter mice. When applied as a 20% solution
0220d -30- 04/17/90
-------
Table 6-1
Incidence of Tumors In Sprague-Dawley Rats Dosed With
o £-LM iui upiieuu i diiu/ui tiuyiuicd diiu niirdie tcwuj-
ro
ro
o
Treatment**
(ppm)
Control
Pre- and Postnatal (No. EUN)
5
50
500
EUN Only
Prenatal «• EUN
5
50
^ 500
Postnatal * EUN
5
50
500
Pre- and Postnatal * EUN
5
50
500
Days
Hean
422
422
420
421
302
282
268
276
282
325
300
245
256
259
to Tumor
1 SE
± *o
t 60
• 59
± 61
± I*
» 15
» 17
± 17
* 15
» 17
i 22
t 14C
I 14'
lumor
lotal
3d
2d
4d
5d
58
69
63
57
7/d
54
33d
85d
63
68
Incidence (%)
Hale
7d
4d
4d
4d
54
75d
50
75d
83d
63
39
92d
85d
77d
F ema 1 e
Od
Od
4d
7d
63
63
75
39d
71
46
25d
79
50
60
No. Rats/Group
Hale
30
24
24
28
28
24
24
28
24
24
28
24
24
30
Female
30
24
24
28
24
24
24
28
24
24
24
24
24
30
a From: Exon and Koller, 1983b
D 2-Chlorophenol was administered In the drinking water. Prenatal administration was done by dosing
5 dams from weaning through parturition or postnatally from weaning (21 Days). ENU was administered
^ as ethylurea 1n the feed (3.18X) and 1-ppm nitrate to the water.
««j
^.
o c £.10 compared to ENU positive control by analysis of variance (lease-square means).
d p<.10 compared to ENU positive control by chl-square test.
-------
In dloxane to the backs of the uninitiated mice twice weekly for 12 weeks,
28/30 mice survived; 46% of these mice developed paplllomas, but none
developed carcinomas. A dloxane-treated vehicle control group was not
reported. When applied twice weekly for 15 weeks as a 20% solution In
benzene following Initiation with 0.3% OMBA In benzene, 31/35 mice survived
compared with 15/20 similarly Initiated vehicle control mice. A
benzene-treated vehicle control group was not reported. Of the survivors,
61% had paplllomas, compared with 7% of the controls; 10% had carcinomas,
whlle-inone were seen In the controls (Table 6-2).
6.3. ' MUTAGENICITY
In a modification of the prelncubatlon procedure of the Salmonella
assay, concentrations of 10-1000 yg/plate of reagent grade 2-chlorophenol
dissolved 1n dimethylsulfoxide (control plate was solvent only) were
negative when tested 1n strains TA100, TA1535, TA1537 and TA98, with and
without S-9 metabolic activation (Haworth et al., 1983).
Acute oral doses of 75-300 mg/kg 1n CO-1 mice did not Induce SCE or
affect DNA synthesis (Borzelleca, 1983).
Oral administration of 130 mg/kg of 2-chlorophenol to Sprague-Oawley
rats every other day for 1 week resulted In a 5-fold Increase 1n chromatld
deletions 1n bone marrow cells (Chung, 1978). After exposures of 2-3 weeks,
there was complete Inhibition of mitosis 1n the cells.
6.4. DEVELOPMENTAL TOXICITY
Pertinent data regarding the teratogenldty of 2-chlorophenol from
either oral or Inhalation exposure were not located In the available
literature cited In Appendix A.
0220(1 -32- 04/17/90
-------
Table 6-2
The Incidence of Tumors 1n Initiated and Uninitiated Mice
Treated WHh 2-Chlorophenold
Treatment
No. Mice
(Survivors/Treated)
No. with
paplllomas
No. with
carcinomas
Control (No treatment)
No Initiator;
20% chlorophenol
1n'da1oxane&
3% OMBA In benzene;
20% chlorophenol In
benzene^
25/25
28/30
31/35
13 (46%)
19
3 (10%)
aFrom: Boutwell and Bosch (1959)
''Benzene and dloxane vehicle control groups were not reported
cp>.05 compared with uninitiated mice by Fisher Exact Test
0220d
-33-
04/20/90
-------
6.5. OTHER REPRODUCTIVE EFFECTS
Exon and Roller (1982, 1983b, 1985) performed several studies In which
reproductive parameters were measured In groups of 12-20 female Sprague-
Oawley rats exposed to 2-chlorophenol (97-98% pure) In drinking water at
concentrations of 0, 5, 50 and 500 ppm. In all cases, dams were exposed
from 3 weeks of age through breeding at 90 days (to untreated males); expo-
sure continued until 3 weeks postparturItlon. Untreated negative controls
were also Included. Reproductive parameters evaluated were percent
conception, Utter size, number of stillbirths, birth and weaning weights
--t
and survival to weaning. Records of body weights and hematologlc data were
taken on the pups at weaning.
Results Indicated that percent conception was greater In all treated
groups (9/12, 9/12, 12/14 for 5, 50 and 500 ppm treated groups, respec-
tively) than 1n the untreated control group (8/12), but these results were
not statistically significant. Utter sizes (live and stillborn) were
significantly decreased and percent of stillbirths was significantly greater
in the dams given 500 ppm 2-chlorophenol. Birth weights (live pups only),
body weights at weaning and survival to weaning (exclusive of stillborn
pups) were not affected by the treatment. Body weight gains of the dams
also were not affected. There were no statistically significant
treatment-related effects on hematologlc parameters. No effects were seen
at <50 ppm.
In addition, Exon and Koller (1985) studied the Immune function In
another group of pups whose exposure was continued postnatally. These pups
were weaned at 3 weeks; exposure to 2-chlorophenol was continued for a
subsequent 12-15 weeks. The 1mmunolog1cal status of each animal was
evaluated by testing Us ability to elicit three major types of Immune
0220d -34- 04/17/90
-------
responses (humoral Immunity, cell-mediated Immunity and macrophage
function). Each Immune function test was performed on four male and four
female offspring from each treatment group. Body, liver, spleen and thymus
weights were also recorded at the time of sacrifice.
Rats treated with the 2-chlorophenol did not respond differently than
their corresponding controls In any of the Immune functions evaluated In
these Investigations. None of the treatment groups demonstrated any
statistically significant alterations In either whole body or individual
organ weights.
6.6. SUMMARY
No Information was located concerning the subchronlc or chronic Inhala-
tion toxlclty of 2-chlorophenol.
In rats dosed by gavage with 2-chlorophenol at 65 or 130 mg/kg for 3
weeks, there were reductions 1n weight gains and Increases 1n liver weights
when compared with controls (Chung, 1978). Hematologlcal effects and
hepatic degeneration were also noted at both treatment levels.
In reports of a subchronlc drinking water study (Exon and Koller, 1983a,
1985) 1n which rats were exposed to 2-chlorophenol pre-, post-, and pre- and
postnatally through the dams and then In the drinking water at levels of 0,
5, 50 and 500 ppm for <15 weeks, no Immunological effects were observed at
any level.
In a chronic drinking water study (Exon and Koller, 1985) In which rats
were exposed to 2-chlorophenol prenatally through their dams and then In the
drinking water at levels of 0, 5, 50 and 500.' ppm for <2 years, hemoglobin
levels. RBC counts and PCV were all significantly higher 1n the groups
exposed to 500 ppm than In controls.
Chlorophenols reportedly Irritate the skin and eyes, and the dusts
Irritate the respiratory tract (Frelter, 1981). In humans, 2-chlorophenol
0220d -35- 04/17/90
-------
causes severe burns, liver and kidney damage, narcosis and respiratory
depression (Davis et al., 1959).
Oral LOrgS of 670, 346-670 and 440 mg/kg have been reported for the
rat (Oelchmann, 1943), the mouse (Borzelleca et al., 1985; Bubnov. 1969) and
the blue fox (Bubnov, 1969), respectively. A single oral dose of 300 mg/kg
caused kidney and liver damage 1n Gunn rats, which appeared to be more
sensitive to the compound than Sprague-Oawley rats (Houser, 1983). An oral
dose of 63 mg/ky caused motor Impairment In CD-I mice within 5 minutes, and
a dose of 1 mg/kg produced behavioral change after 2 days (Borzelleca,
1983). A gavaged dose of 175 mg/kg resulted In 80% mortality 1n mice, with
a statistically significant weight loss before death; hyperactlvUy was seen
at lower doses (Kallman et al., 1982). In rats, a median lethal
Intraperltoneal dose of 230 mg/kg caused excited behavior and convulsions,
with a decrease In body temperature (Farquharson et al.. 1958).
No Information on cardnogenldty of 2-chlorophenol from Inhalation
exposures could be located. A carc1nogen1dty-cocarc1nogen1c1ty drinking
water study (Exon and Koller, 1985) In which rats were exposed to 2-chloro-
phenol hi utero and then In drinking water at concentrations <500 ppm was
negative for cardnogenldty after 2 years of exposure. In the same study,
2-chlorophenol appeared to promote the cardnogenldty of ENU, Increasing
the tumor Incidence and decreasing the t1me-to-tumor 1n male rats. Dermal
application of 2-chlorophenol following Initiation by OMBA promoted the
formation of skin tumors 1n mice (Boutwell and Bosch. 1959).
Up to 1000 yg/plate 2-chlorophenol was -negative for mutagenldty 1n
four strains of Salmonella typhlmuMum. with and without metabolic activa-
tion (Haworth et al., 1983). It did not Induce SCEs or affect DNA synthesis
In mice dosed with 75-300 mg/kg (Borzelleca, 1983). Chromatld deletions
0220d -36- 04/17/90
-------
were reported In rat bone marrow cells from treatment with 130 mg/kg every
other day for 1 week (Chung, 1978).
No Information on the teratogenlclty of 2-chlorophenol could be located.
Reproductive effects were reported 1n rats exposed to 2-chlorophenol 1n
drinking water from weaning through breeding and lactation (Exon and Koller,
1982; 1985). Reduced Utter sizes and Increased number of stillbirths were
seen 1n rats exposed to 500 ppm 2-chlorophenol; these effects were not seen
at <50 ppm.
0220d -37- 04/17/90
-------
7. EXISTING GUIDELINES AND STANDARDS
7.1. HUMAN
A verified RfO for 2-chlorophenol of 0.005 mg/kg/day (U.S. EPA, 1988)
was based upon reproductive effects In the rat study by Exon and Koller
(1982).
The U.S. EPA (1980b) established an ambient water quality criterion of
0.1 yg/l for 2-chlorophenol, based upon organoleptk data from a report
by 01etz and Traud (1978). WHO (1984) suggested a maximum level of 1
ug/l for 2-chlorophenol In drinking water based on organoleptk consid-
erations.
A DUEL of 0.175 mg/l was determined by the U.S. EPA (1986b), based on
the subchronlc rat reproduction study by Exon and Koller (1982).
7.2. AQUATIC
Guidelines and standards for the protection of aquatic life from
exposure to 2-chlorophenol were not located In the available literature
cited 1n Appendix A.
0220d -38- 05/03/90
-------
8. RISK ASSESSMENT
8.1. CARCINOGENICITY
8.1.1. Inhalation. Pertinent data regarding the cardnogenlclty of
2-chlorophenol to animals or humans from Inhalation exposure were not
located In the available literature cited 1n Appendix A.
8.1.2. Oral. Exon and Roller (1985) reported negative results In a
cardnogenlclty study of 2-chlorophenol 1n Sprague-Dawley rats. Rats were
exposed to the compound ^n utero through lactation, and then In drinking
water, at concentrations of 0, 5, 50'or 500 ppm for <24 months.
•*
In the same study (Exon and KolVer, 1985), the ability of 2-chlorophenol
to potentiate the cardnogenlclty of ENU, a known carcinogen, was examined.
Rat dams were exposed to precursors of ENU during gestation. Offspring were
exposed to 2-chlorophenol prenatally through the dams, postnatally 1n the
drinking water or both. In all groups of 2-chlorophenol-exposed males.
tumor Incidence Increased and time-to-tumor decreased when compared with
rats exposed only to ENU.
8.1.3. Other Routes. Boutwell and Bosch (1959) found that dermal appli-
cation of 2-chlorophenol to mice following Initiation by DM8A promoted the
formation of skin tumors.
8.1.4. Weight of Evidence. The only available cardnogenlclty study of
2-chlorophenol Is a negative drinking water study In which rats were exposed
pre-, post- or both pre- and postnatally; exposure was continued through 2
'years with drinking water containing 2-chlorophenol <500 ppm (Exon and
Roller. 1985).
The U.S. EPA (1987) recommended that 2-chlorophenol be classified In
U.S. EPA Group 0 (U.S. EPA, 1986d) (I.e.. cannot be classified as to
cardnogenlclty In humans). More recent data were not located that would
change this assessment.
0220d -39- 05/03/90
-------
8.1.5. Quantitative Risk Estimates.
8.1.5.1. INHALATION — Lack of data precludes estimation of carcino-
genic potency from Inhalation exposure to 2-chlorophenol.
8.1.5.2. ORAL -- The only cardnogenlclty data located regarding
2-chlorophenol were the negative drinking water studies 1n rats by Exon and
Roller (1983b, 1985). The carcinogenic potency from oral exposure to
2-chlorophenol cannot be quantitatively estimated.
8.2. SYSTEMIC TOXICITY
The designation "Rec." In the following sections refers to data records
compiled 1n Section C.2. of Appendix C for the generation of dose/duration-
response graphs.
8.2.1. Inhalation Exposure.
8.2.1.1. LESS THAN LIFETIME (SUBCHRONIC) — Pertinent data regarding
the subchronlc Inhalation toxlclty of 2-chlorophenol were not located 1n the
available literature cited 1n Appendix A; therefore, derivation of an RfO
for subchronlc Inhalation exposure Is not possible.
8.2.1.2. CHRONIC — Pertinent data regarding subchronlc or chronic
Inhalation toxlclty of 2-chlorophenol were not located In the available
literature dted 1n Appendix A; therefore, derivation of an RfD for chronic
Inhalation exposure 1s not possible.
8.2.2. Oral Exposure.
8.2.2.1. LESS THAN LIFETIME (SUBCHRONIC) — Data from sufficiently
comprehensive subchronlc oral studies of 2-chlorophenol In which adequate
parameters of toxlclty were measured were not available. Chung (1978)
reported decreased weight gain, liver and hematologlc effects In rats
treated by gavage at 65 or 130 mg/kg/day for 3 weeks. No 1mmunolog1ca1
0220d -40- 04/17/90
-------
effects were found In rats exposed both pre- and postnatally to 2-chloro-
phenol In the drinking water at levels <500 ppm (NOEL) (Rec. #11} for 12-15
weeks (Exon and Koller, 1983a, 1985). In a reproductive study. Exon and
Koller (1982) found a decrease In litter sizes and an Increase In still-
births in rats given drinking water containing 500 ppm of 2-chlorophenol
(Rec. #2) from 3 weeks of age through breeding and lactation. These effects
were not observed at the next lower dose of 50 ppm, a NOAEL (Rec. #1).
The reproductive NOAEL of 50 ppm was used to derive a chronic RfD of
0.005 mg/kg/day or 0.4 mg/day for a 70 kg human (U.S. EPA, 1986b). Because
the subchronlc toxldty data base for 2-chlorophenol was judged to be
Inadequate to calculate an RfD, the chronic oral RfO (Section 8.2.2.2.) was
adopted as the subchronlc oral RfO (U.S. EPA, 1987). As discussed In
Section 8.2.2.2., confidence In the key study, data base and the RfD are low.
8.2.2.2. CHRONIC — Exon and Koller (1985) reported hematologlc
effects 1H rats provided drinking water containing 2-chlorophenol at 500 ppm
(LOAEL) (Rec. #3) for <24 months. These effects were not observed In rats
exposed to 50 ppm (NOAEL) (Rec. #4). Although the protocol stated that a
complete hlstopathologlcal examination was performed, noncancer results were
not presented. In studies by Exon and Koller (1982, 1985), reproductive
effects were noted In female rats exposed to 500 ppm 2-chlorophenol In
drinking water from 3 weeks of age through breeding and parturition (Rec.
#2). These effects were not seen In rats exposed to 50 ppm (NOAEL) (Rec.
#1). The data from the 1982 study were used by the Office of Drinking Water
as the basis for an oral RfO (U.S. EPA, 198&b). Based on the assumption
that a rat drinks the equivalent of 10% of Us body weight In water dally,
500 ppm was transformed to an estimated dosage of 50 mg/kg/day (LOAEL), and
50 ppm to 5 mg/kg/day (NOAEL). A verified RfO of 0.005 mg/kg/day was
0220d -41- 04/17/90
-------
derived using an uncertainty factor of 1000 (10 for Interspecles extrapola-
tion, 10 to protect unusually sensitive individuals and 10 for use of data
from a subchronlc study). The assumption that rats drink water equivalent
to 10% of their weight dally differs from the suggested water consumption
guidelines for rats (U.S. EPA, 1986c) where water consumption = 0.049
l/day with a reference body weight of 0.35 kg. These factors would result
1n a transformation of the NOAEL of 50 ppm to 7 mg/kg/day.
U.S. EPA (1988) considered confidence In the key study low because only
reproductive and hematological endpolnts were evaluated. Confidence In the
data base is low because no other adequate subchronlc, chronic or develop-
mental toxldty data were available. Confidence In the RfO was low because
of low confidence In the key study and data base.
Confidence In the RfO 1s further eroded by reports of altered behavior
In mice treated with 2-chlorophenol by gavage. In a 14-day exposure study,
Kallman et al. (1982) reported hyperactlvlty In mice treated with 35 or 69
mg/kg/day from day 4 until treatment was terminated. Because 35 mg/kg/day
was the lowest level tested, a NOAEL for this effect was not determined. In
another study from this laboratory, Borzelleca (1983) reported that 63 mg/kg
administered as a single dose was the ED.- for motor Impairment, which
peaked In Intensity at 5 minutes after treatment. Alterations In operant
behavior occurred after as few as two gavage doses >1 mg/kg/day. The
testing protocol was not presented, however, and these data cannot be
adequately evaluated.
0220d -42- 05/03/90
-------
9. REPORTABLE QUANTITIES
9.1. BASED ON SYSTEMIC TOXICITY
The U.S. EPA (1983) determined that the toxlclty data for 2-chlorophenol
were Inadequate for deriving an RQ. However, more recent data on reproduc-
tive effects In rats (Exon and Koller, 1982) were deemed appropriate for RQ
derivation (U.S. EPA. 1987). The RQ was derived from a dose of 500 ppm
2-chlorophenol In drinking water provided to rat dams from 3 weeks of age
through lactation, which resulted In significantly reduced Utter sizes.
The equivalent human dose was 12 mg/kg/day, based on a dally water consump-
tion conversion factor of 0.049 I/day for rats (U.S. EPA, 1986c) and a
transformed animal dose of 70 mg/kg/day. Multiplying the human body weight
of 70 kg by the transformed human dose results 1n a human MED of 840 mg/day,
which corresponds to an RV of 1.1. With an RV of 8 for the observed
fetotoxldty, a CS of 9 was derived, which corresponds to an RQ of 1000.
More recent toxldty data for 2-chlorophenol were not located, and the RQ of
1000 previously derived by U.S. EPA (1987) 1s presented In Table 9-1.
9.2. BASED ON CARCINOGENICITY
As reviewed In Chapter 6, cardnogenldty data for 2-chlorophenol are
limited to the negative drinking water studies In rats by Exon and Koller
(1983b, 1985). The U.S. EPA (1987) recommended that 2-chlorophenol be
classified In U.S. EPA Group 0 (U.S. EPA, 1986d) — I.e., cannot be
classified as to cardnogenldty 1n humans. Since potency factors cannot be
derived for the chemical, a hazard ranking based on cardnogenldty Is not
possible for this compound.
0220d -43- 05/03/90
-------
TABLE 9-1
2-Chlorophenol
Minimum Effective Dose (MEO) and Reportable Quantity (RQ)
Route: oral 1n drinking water
Spedes/sex: rat/female
Dose*: 840 mg/day
Duration: from 3 weeks of age through parturition
Effect: decreased Utter size; Increased number of
stillbirths
RVd: 1.1
RVe: 8
CS: 9
RQ: 1000
Reference: Exon and Koller, 1982
•Equivalent human dose
0220d -44- 04/17/90
-------
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phenol, 2,4,6-trlchlorophenol) (Revtsed). EPA-440/4-85-007. NTIS
PB85-211951. Arthur 0. Little Inc., Cambridge. MA. 119 p.
Shlgeoka, T., Y. Sato, Y. Takeda, K. Yoshlda and F. Yamauchl. 1988. Acute
toxlcity of chlorophenols to green algae, Selenastrutn capMcornutum and
Chlorella vulqarls and quantitative structure activity relationships.
Environ. Toxlcol. Chem. 7(10): 847-854.
0220d -57- 04/17/90
-------
SHhole, 8.8., D.T. Will lams. C. Lastorla and J.L. Robertson. 1986. Deter-
mination of halogenated phenols In raw and potable water by selected Ion gas
chromatography-mass spectrometry. J. Assoc. Off. Anal. Chem. 69: 466-473.
Smith, J.H.. D. Mackay and C.W.K. Nig. 1983. Volatilization of pesticides
from water. Res. Rev. 85: 73-88.
Spencer, B. and R.T. HI!Hams. 1950. Studies In detoxlcatlon. The metabo-
lism of halogenobenzenes. Blochem. J. 47: 279-284.
•i
Stepan, S., J.F. Smith and M. Rlha. 1981. Movement and chemical change of
organic pollutants 1n an aquifer. Austral. Water Resources Council Conf.
Ser. 1: 415-422.
Sufllta, J.M. and G.O. Miller. 1985. Mlcroblal metabolism of chloro-
phenoHc compounds \r\ groundwater aquifers. Environ. Toxlcol. Chem. 4:
751-758.
Suntlo. L.R., W.Y. Sh1u and 0. Mackay. 1988. A review of the nature and
properties of chemicals present In pulp mill effluents. Chemosphere. 17:
1249-1269, 1272-1281. 1284-1285, 1288-1290.
Tabak, H.H., S.A. Quave. C.I. Mashnl and E.F. Barth. 1981. Blodegradabll-
1ty studies with organic priority pollutant .-compounds. J. Water Pollut.
Control Fed. 53: 1503-1518.
0220d -58- 04/17/90
-------
Thomas, R.G. 1982. Volatilization from water. Ijr. Handbook of Chemical
Property Estimation Methods, W.J. Lyman, W.F. Reehl and D.H. Rosenblatt, Ed.
McGraw Hill Book Co., New York, NY. p. 15-1 to 15-21, 15-26 to 15-30.
Tlssot, A., P. Boule, J. Lemalre, S. Lambert and J.C.Palla. 1985. Photo-
chemistry and environment: 10. Evaluation of the toxlclty of the phototrans-
formatlon products of hydroqulnone and chlorophenols In aqueous environ-
ments. Chemosphere. 14(9): 1221-1230.
Trabalka, J.R. and M.B. Burch. 1978. Investigation of the effects of halo-
genated organic compounds produced 1n cooling systems and process effluents
on aquatic organisms. Environ. Impact Health Eff. p. 163-173.
TSCAPP. 1989. Computer Printout of Non-Confidential Production Data from
TSCA Inventory OPTS, CIO, U.S. EPA, Washington, OC. Online: 3/28/89.
U.S. EPA. 1980a. Guidelines and Methodology in the Preparation of Health
Effect Assessment Chapters of the Consent Decree Drinking Water Criteria
Document. Federal Register. 45(231): 79347-79357.
U.S. EPA. 1980b. Ambient Water Quality Criteria Document for 2-Chloro-
phenol. Prepared by the Office of Health and Environmental Assessment,
Environmental Criteria and Assessment Office, Cincinnati, OH for the Office
of Water Regulations and Standards, Washington* OC. EPA 440/5-80-034. NTIS
PB81-117459.
0220d -59- 04/17/90
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U.S. EPA. 1983. Reportable Quantity Document for 2-Chlorophenol. Prepared
by the Office of Health and Environmental Assessment, Environmental Criteria
and Assessment Office, Cincinnati, OH for the Office of Emergency and
Remedial Response, Washington, DC.
U.S. EPA. 1984. Methodology and Guidelines for Ranking Chemicals Based on
Chronic Toxldty Data. Prepared by the Office of Health and Environmental
Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH for
the Office of Emergency and Remedial Response, Washington, DC.
U.S. EPA. 1986a. Methodology for Evaluating Reportable Quantity Adjust-
ments Pursuant .to CERCLA Section 102. Prepared by Carcinogen Assessment
Group, Office of Health and Environmental Assessment for the Office of
Emergency and Remedial Response, Washington, OC.
U.S. EPA. 1986b. Drinking Water Criteria Document for Chlorophenols.
Prepared by the Office of Health and Environmental Assessment, Environmental
Criteria and Assessment Office, Cincinnati, OH for the Office of Drinking
Water, Washington, DC.
U.S. EPA. 1986c. Reference Values for Risk Assessment. Prepared by the
Office of Health and Environmental Assessment, Environmental Criteria and
Assessment Office, Cincinnati, OH for the Office of Solid Waste, Washington,
DC.
U.S. EPA. 1986d. Guidelines for Carcinogen Risk Assessment. Federal
Register. 51(185): 33992-34003.
0220d -60- 05/03/90
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U.S. EPA. 1987. Health and Environmental Effects Document for Chlorinated
Phenols. Prepared by the Office of Health and Environmental Assessment,
Environmental Criteria and Assessment Office, Cincinnati, OH for the Office
of Solid Waste and Emergency Response, Washington, DC.
U.S. EPA. 1988. Integrated Risk Information System (IRIS). Reference Dose
(RfD) for Oral Exposure for 2-Chlorophenol. Online. (Verification date
1/20/88.) Office of Health and Environmental Assessment, Environmental
o
Criteria and Assessment Office, Cincinnati, OH.
U.S. EPA/OWRS. 1986. Guidelines for Deriving Numerical National Water
Quality Criteria for the Protection of Aquatic Organisms and Their Uses.
U.S. EPA, Washington, DC. PB85-227049/XA8. p. 22-58.
Wang, W. and P. Reed. 1984. NHrobacter bloassay for aquatic toxldty.
Drug Chem. Toxlcol. 1: 309-325.
Weast, R.C., M.J. Astle and W.H. Beyer. 1988. CRC Handbook of Chemistry
and Physics, 69th ed. CRC Press, Inc., Boca Raton, FL. p. C-408.
Wegman, R.C.C. and A.W.H. Hofstee. 1979. Chlorophenols In surface waters
of the Netherlands (1976-1977). Water Res. 13: 651-657.
«
Wegman, R.C.C. and H.H. van den Broek. 1$83. Chlorophenols In river
sediment 1n the Netherlands. Water Res. 17: 227-230.
0220d -61- 05/03/90
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WHO (World Health Organization). 1984. Guidelines for' Drinking Water
Quality. Vol. 2. Health Criteria and Other Supporting Information. WHO,
Geneva, p. 221-239.
Wlndholz, M., S. Budavarl, R.F. Blumettl and E.S. Otterbeln. 1983. The
Merck Index. Merck and Co., Inc., Rahway, NJ. p. 302-303.
Yasuhara, A. and M. MorUa. 1988. Formation of chlorinated aromatic hydro-
carbons by thermal decomposition of vlnylldene chloride polymer. Environ.
Sd. Technol. 22: 646-650.
Young, D.R. 1978. Priority pollutants In municipal wastewaters. Ann.
Rep.-South. CA. Coastal Water Res. ProJ. p. 103-112.
0220d -62- 04/17/90
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APPENDIX A
LITERATURE SEARCHED
This HEED Is based on data Identified by computerized literature
searches of the following:
CHEMLINE
TSCATS
CASR online (U.S. EPA Chemical Activities Status Report)
TOXLINE
T.OXLIT
TOXLIT 65
RTECS
OHM TADS
STORE!
SRC Environmental Fate Data Bases
SANSS
AQUIRE
TSCAPP
NTIS
Federal Register
CAS ONLINE (Chemistry and Aquatic)
HSOB
These searches were conducted In May, 1988, and the following secondary
sources were reviewed:
ACGIH (American Conference of Governmental Industrial Hyglenlsts).
1986. Documentation of the Threshold Limit Values and Biological
Exposure Indices, 5th ed. Cincinnati, OH.
ACGIH (American Conference of Governmental Industrial Hyglenlsts).
1987. TLVs: Threshold Limit Values for Chemical Substances In the
Work Environment adopted by ACGIH with Intended Changes for
1987-1988. Cincinnati, OH. 114 p.
Clayton, G.O. and F.E. Clayton, Ed. 1981. Patty's Industrial
Hygiene and Toxicology, 3rd rev. ed., Vol. 2A. John Wiley and
Sons. NY. 2878 p.
Clayton, G.O. and F.E. Clayton, Ed. 1981. Patty's Industrial
Hygiene and Toxicology, 3rd rev. ed., Vol. 2B. John WHey and
Sons. NY. p. 2879-3816.
0220d -63- 04/17/90
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Clayton, G.O. and F.E. Clayton, Ed. 1982. Patty's" Industrial
Hygiene and Toxicology, 3rd rev. ed., Vol. 2C. John WUey and
Sons, NY. p. 3817-5112.
Grayson, M. and 0. Eckroth, Ed. 1978-1984. K1rk-0thmer Encyclo-
pedia of Chemical technology, 3rd ed. John Wiley and Sons, NY. 23
Volumes.
Hamilton, A. and H.L. Hardy. 1974. Industrial Toxicology, 3rd ed.
Publishing Sciences Group, Inc., Littleton, MA. 575 p.
IARC (International Agency for Research on Cancer). IARC Mono-
graphs on the Evaluation of Carcinogenic Risk of Chemicals to
Humans. IARC, WHO, Lyons, France.
Jaber, H.M., W.R. Mabey, A.T. L1eu, T.W. Chou and H.L. Johnson.
1984. Data acquisition for environmental transport and fate
screening for compounds of Interest to the Office of Solid Waste.
EPA 600/6-84-010. NTIS PB84-243906. SRI International, Menlo
Park, CA.
NTP (National Toxicology Program). 1987. Toxicology Research and
Testing Program. Chemicals on Standard Protocol. Management
Status.
Ouellette. R.P. and J.A. King. 1977. Chemical Week Pesticide
Register. McGraw-Hill Book Co., NY.
Sax, I.N. 1984. Dangerous Properties of Industrial Materials, 6th
ed. Van Nostrand Relnhold Co., NY.
SRI (Stanford Research Institute). 1987. Directory of Chemical
Producers. Menlo Park, CA.
U.S. EPA. 1986. Report on Status Report In the Special Review
Program, Registration Standards Program and the Data Call In
Programs. Registration Standards and the Data Call In Programs.
Office of Pesticide Programs, Washington, DC.
USITC (U.S. International Trade Commission). 1986. Synthetic
Organic Chemicals. U.S. Production and Sales, 1985, USITC Publ.
1892, Washington, DC.
Verschueren. K. 1983. Handbook of Environmental Data on Organic
Chemicals, 2nd ed. Van Nostrand Reinhold Co., NY.
Wlndholz. M., Ed. 1983. The Merck Index... 10th ed. Merck and Co.,
Inc., Rahway, NJ.
Worthing, C.R. and S.B. Walker, Ed. 1983. The Pesticide Manual.
British Crop Protection Council. 695 p.
0220d -64- 04/17/90
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In addition, approximately 30 compendia of aquatic toxlclty data were
reviewed. Including the following:
Battelle's Columbus Laboratories. 1971. Hater Quality Criteria
Data Book. Volume 3. Effects of Chemicals on Aquatic Life.
Selected Data from the Literature through 1968. Prepared for the
U.S. EPA under Contract No. 68-01-0007. Washington, DC.
Johnson, H.W. and M.T. Finley. 1980. Handbook of Acute ToxlcHy
of Chemicals to Fish and Aquatic Invertebrates. Summaries of
Toxklty Tests Conducted at Columbia National Fisheries Research
Laboratory. 1965-1978. U.S. Dept. Interior, Fish and Wildlife
Serv. Res. Publ. 137, Washington, DC.
McKee, J.E. and H.W. Wolf. 1963. Water Quality Criteria, 2nd ed.
Prepared for the Resources Agency of California, State Water
Quality Control Board. Publ. No. 3-A.
Plmental, D. 1971. Ecological Effects of Pesticides on Non-Target
Species. Prepared for the U.S. EPA, Washington, DC. PB-269605.
Schneider. 8.A. 1979. Toxicology Handbook. Mammalian and Aquatic
Data. Book 1: Toxicology Data. Office of Pesticide Programs, U.S.
EPA. Washington, DC. EPA 540/9-79-003. NTIS P8 80-196876.
0220d -65- 04/17/90
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APPENDIX B
Summary Table for 2-Chlorophenol
o
ru
ro
o
Q.
Species
Inhalation exposure
Subchronlc 10
Chronic ID
Cardnogenlclty 10
Oral exposure
& Subchronlc rat
i
Chronic rat
Cardnogenlclty 10
REPORTABLE QUANTITIES
Based on chronic toxlclty:
o
£ Based on carclnogenUlty:
-j
Exposure
10
10
ID
50 ppm (5 mg/kg/day)
from 3 weeks of age
through parturition
50 ppm (5 mg/kg/day)
from 3 weeks of age
through parturition
10
1000
10
Effect
10
10
10
NOAEL for decreased
litter size, In-
creased stillbirths
NOAEL for decreased
litter size. In-
creased stillbirths
ID
RfO or qi* Reference
ID 10
10 ID
10 ID
0.005 mg/kg/day Exon and
Koller.
0.005 mg/kg/day Exon and
Koller.
10 10
Exon and
Koller.
ID
1982
1982
1982
10 = Insufficient data
-------
APPENDIX C
DOSE/DURATION RESPONSE GRAPHS FOR EXPOSURE TO 2-CHIOROPHENOL
C.I. DISCUSSION
A dose/duration-response graph for oral exposure to 2-chlorophenol
generated by the method of Crockett et al. (1985) using the computer soft-
ware by Durkin and Meylan (1988) developed under contract to ECAO-Clnn1nnat1
Is presented in Figure C-l. Data used to generate this graph are presented
In Section C.2. In the generation of this figure, all responses are
classified as adverse (FEU AEL or LOAEL) or nonadverse (NOEL or NOAEL) for
plotting. For oral exposure, the ordlnate expresses dosage as human equiva-
lent dose. The animal dosage In mg/kg/day Is'multiplied by the cube root of
the ratio of the animal:human body weight to adjust for species differences
In basal metabolic rate (Mantel and Schnelderman, 197S). The result Is then
multiplied by 70 kg, the reference human body weight, to express the human
equivalent dose as mg/day for a 70 kg human.
The boundary for adverse effects (solid line) is drawn by Identifying
the lowest adverse effect dose or concentration at the shortest duration of
exposure at which an adverse effect occurred. From this point, an Infinite
line Is extended upward, parallel to the dose axis. The starting point Is
then connected to the lowest adverse effect dose or concentration at the
next longer duration of exposure that has an adverse effect dose or concen-
tration equal to or lower than the previous one. This process is continued
to the lowest adverse effect dose or concentration. From this point, a line
1s extended to the right, parallel to the duration axis. The region of
adverse effects lies above the adverse effects boundary.
Using the envelope method, the boundary for no adverse effects (dashed
line) Is drawn by identifying the highest no adverse effects dose or concen-
tration. From this point, a line parallel to the duration axis 1s extended
0220d -67- 04/17/90
-------
iwetM
*
* ,.,..-.
s
I
k
C
a
t
9
|k
Z
C i ^ •
f A IP
•
X
J •
C.-*: £M«MI»U
r-»5— ' • < . i MI 1 — • — ' ' |
; r»
•
..__.. « ••* • •
• *7 "'•-..
'. U2 ''•••.
\ ' ,s
— * ***•
r* *
» *.
; \ nl '"i
' 4 _B^^^
, \
\
' >
\
* \
\
0fll •••! «.l 1
•UMN C«UIV MIMTIOM
n-> UWCLOr MTHO»
:
j
1
1
1
•J •
5
j
i
|4 3
•*
J
J
n
j
^
1
i a
Key: F . FEL
A . AEL
n . NOAEL
N . NOEL
Solid line . Adverse Effects Boundary
Dashed line • No Adverse Effects Boundary
FIGURE C.I
Dose/Duration - Response Graph for Oral Exposure
to 2-Chlorophenol: Envelope Method
02204
-68-
04/17/90
-------
to the dose or concentration axis. The starting point Is then connected to
the next lower or equal no adverse effect dose or concentration at a longer
duration of exposure. When this process can no longer be continued, a line
Is dropped parallel to the dose or concentration axis to the duration axis.
The no adverse effects region lies below the no adverse effects boundary.
At either ends of the graph between the adverse effects and no adverse
effects boundaries are regions of ambiguity. The area (1f any) resulting
from Intersection of the adverse effects and no adverse effects boundaries
Is defined as the region of contradiction.
In the censored data method, all no adverse effect points located In the
region of contradiction are dropped from consideration and the no adverse
effect boundary is redrawn so that 1t does not Intersect the adverse effects
boundary and no region of contradiction 1s generated. This method results In
the most conservative definition of the no adverse effects region.
Figure C-l presents the dose-duration response graph generated by the
envelope method. The adverse effects boundary Is defined by five points,
corresponding to an LD5Q In rats of 670 mg/kg (Deichmann, 1943} (Rec. #5),
renal and hepatocellular necrosis In rats from an acute dose of 300 mg/kg
(Houser, 1983) (Rec. #9), an oral L05Q of 346 mg/kg 1n mice (Borzelleca et
al., 1985) (Rec. #6), motor Impairment 1n mice treated by gavage with a
single dose of 63 mg/kg (Borzelleca, 1983) (Rec. #7) and a gavage dose of 1
mg/kg/day for 2 days, explained only as the lowest dose that caused behav-
ioral effects In mice (Borzelleca, 1983) (Rec. |8). The no adverse effects
boundary Is defined by two points, representing no Immunologlcal effects
observed 1n rats at dose levels <50 mg/kg (500 ppm in drinking water)
administered prenatally and continued <15 weeks (Exon and Koller, 1983a,
1985) (Rec. #11), and the other representing a 2-year study by Exon and
0220d -69- 04/17/90
-------
Keller (1985) where no hematologlcal effects were seen In' rats at the 5
mg/kg dosage (50 ppm in drinking water) (Rec. #4). The region of contradic-
tion 1s quite large and cannot be censored because of insufficient data.
C.2. DATA USED TO GENERATE OOSE/DURATION-RESPONSE GRAPHS
C.2.1. Inhalation Exposure. No Inhalation toxlcUy data were located.
C.2.2. Oral Exposure.
Chemical Name: 2-Chlorophenol
CAS Number: 95-57-8
Document Title: Health and Environmental Errects Document on 2-Clilorophenol
Document Number: Pending
Document Date: Pending
Document Type: HEED
RECORD #1
Comment:
Species:
Sex:
Effect:
Route:
Rats
Female
NOEL
Water
Dose: 5.000
Duration Exposure: 90.0 days
Duration Observation: 90.0 days
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
13
0
8
50 ppm (range 0. 5. 50, 500 ppm), assume water consumption
factor of 0.1. Exposure from weaning through breeding,
lactation.
Citation:
RECORD #2:
Comment:
Citation:
Exon and K-oller, 1982, 1985
Species: Rats Dose: 50.
Sex: Female Duration Exposure: 90.
Effect: LOAEL Duration Observation: 90.
Route: Water
Number Exposed: 13
Number Responses: NR
Type of Effect: REPRO
Site of Effect: FETUS
Severity Effect: 8
500 ppm (see previous record); effects were decreased
size and Increased numbers of stillborn.
Exon and Holler, 1982, 1985
000
0 days
0 days
litter
0220d
-70-
04/17/90
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RCCORO #3:
Comment:
Citation:
Species:
Sex:
Effect:
Route:
Rats
Both
LOAEL
Water
Dose: ';- 50.000
Duration Exposure: 24.0 months
Duration Observation: 24.0 months
Number Exposed: NR
Number Responses: NR
Type of Effect: HEMAT
Site of Effect: BLOOD
Severity Effect: 1
500 ppm (range 0, 5, SO, 500 ppm). Assumed water consumption
factor of 0.1. No other noncancer endpolnts evaluated.
Exon and Koller, 1985
RECORD #4:
Comment:
Citation:
Species:
Sex:
Effect:
Route:
Rats
Both
NOEL
Hater
Dose: 5.000
Duration Exposure; 24.0 months
Duration Observation: 24.0 months
NR.
0
Number Exposed:
Number Responses
Type of Effect:
Site of Effect:
Severity Effect:
50 ppm (see previous record).
Exon and Koller, 1985
RECORD #5
Comment:
Citation:
Specles:
Sex:
Effect:
Route:
Rats
NS
PEL
Gavage
Dose:
Duration
Duration
Exposure:
Observation:
670.000
1.0 days
1.0 days
Number Exposed: NR
Number Responses: NR
Type of Effect: DEATH
SHe of Effect: BODY
Severity Effect: 10
dose.
Oelchmann, 1943
0220d
71
04/17/90
-------
RECORD #6:
Comment:
Citation:
Comment:
Citation:
RECORD #8:
Comment:
Citation:
Species:
Sex:
Effect:
Route:
Mice
Both
PEL
Gavage
Dose: 346.000
Duration Exposure: 1.0 days
Duration Observation: 14.0 days
Number Exposed: 20
Number Responses: NR
Type of Effect: DEATH
Site of Effect: BODY
Severity Effect: 10
1050 dose.
Borzelleca et al., 1985
RECORD #7:
Species:
Sex:
Effect:
Route:
Mice
Both
AEL
Gavage
Dose: 63.000
Duration Exposure: 1.0 days
Duration Observation: 14.0 days
Number Exposed: NR
Number Responses: NR
Type of Effect: MOTOR
Site of Effect: • MSKEl
Severity Effect: 9
£050 dose for Impaired motor function.
Borzelleca, 1983
Species:
Sex:
Effect:
Route:
Mice
NS
LOAEL
Gavage
Dose:
Duration
Duration
Exposure:
Observation;
1.000
2.0 days
2.0 days
Number Exposed: NR
Number Responses: NR
Type of Effect: BEHAV
Site of Effect: BODY
Severity Effect: 7
Lowest dose producing behavioral changes after 2 days exposure
Borzelleca, 1983
0220d
-72-
04/17/90
-------
RECORD #9:
Comment:
Citation:
Species:
Sex:
Effect:
Route:
Rats
NS
PEL
Oral. NOS
Number Exposed: NR
Number Responses: NR
Type of Effect: NECHU
Site of Effect: KIONY
Severity Effect: 6
Oose: " 300.000
Duration Exposure: 1.0 days
Duration Observation: 1.0 days
NR
NR
NhCRO
LIVER
5
Metabolism study: tentrilobular hepatic Metro*Is
rats; renal necrosis In 75% of rats.
Houser, 1983
In 50% of
RECORD #10:
Comment:
Citation:
RECORD #11:
Species: Rats
Sex: NS
Effect: LOAEL
Route: Oral, NOS
Number Exposed: NR
Number Responses: NR
Type of Effect: WGTDC
SHe of Effect: BODY
Severity Effect: 4
Range 65 and 130 mg/kg/day
Chung, 1978
Species: Rats
Sex: Both
Effect: NOEL
Route: Water
Dose: 65.000
Duration Exposure: 3.0 weeks
Duration Observation: 3.0 weeks
NR
NR
ATROP
LIVER
4
Oose: 50.000
Duration Exposure: 90.0 days
Duration Observation: 90.0 days
Comment:
Citation;
Number Exposed: NR
Number Responses: 0
Type of Effect:
SHe of Effect:
Severity Effect: 3
No Immune effects seen at levels <500 ppm
(50 mg/kg/day); range 0, 5, 50, 500 ppm.
Exon and Koller, 19S3a
in drinking water
0220d
-73-
04/17/90
-------
RECORD #12:
Coninent:
Citation:
Species: Mice
Sex: NS
Effect: LOAEL
Route: Gavage
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
NR
NR
FUNS
BRAIN
7
Dose: "• 35.000
Duration Exposure: 4.0 days
Duration Observation: 4.0 days
Hyperactivity that stopped when treatment ceased. Mortality
occurred at 175 mgAg/day.
Kailman et al., 1982
NS » Not.stated
0220d
-74-
04/17/90
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