United Siates
Environmental Protection
Agency
Office of Water
Regulations and Standards
Criteria and Standards Division
Washington DC 20460
EPA 440,5-80-042
October '980
Ambient
Water Quality
Criteria for
2,4-dichlorophenol
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AMBIENT WATER QUALITY CRITERIA FOR
2,4-DICHLOROPHENOL
Prepared By
U.S. ENVIRONMENTAL PROTECTION AGENCY
Office of Water Regulations and Standards
Criteria and Standards Division
Washington, D.C.
Office of Research and Development
Environmental Criteria and Assessment Office
Cincinnati, Ohio
Carcinogen Assessment Group
Washington, D.C.
Environmental Research Laboratories
Corvalis, Oregon
Duluth, Minnesota
Gulf Breeze, Florida
Narragansett, Rhode Island
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DISCLAIMER
This report has been reviewed by the Environmental Criteria and
Assessment Office, U.S. Environmental Protection Agency, and approved
for publication. Mention of trade names or commercial products does not
constitute endorsement or recommendation for use.
AVAILABILITY NOTICE
This document is available to the public through the National
Technical Information Service, (NTIS), Springfield, Virginia 22161.
11
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FOREWORD
Section 304 (a)(l) of the Clean Water Act of 1977 (P.L. 95-217),
requires the Administrator of the Environmental Protection Agency to
publish criteria for water quality accurately reflecting the latest
scientific knowledge on the kind and extent of all identifiable effects
on health and welfare which may be expected from the presence of
pollutants in any body of water, including ground water. Proposed water
quality criteria for the 65 toxic pollutants listed under section 307
(a)(l) of the Clean Water Act were developed and a notice of their
availability was published for public comment on March 15, 1979 (44 FR
15926), July 25, 1979 (44 FR 43660), and October 1, 1979 (44 FR 56628).
This document is a revision of those proposed criteria based upon a
consideration of comments received from other Federal Agencies, State
agencies, special interest groups, and individual scientists. The
criteria contained in this document replace any previously published EPA
criteria for the 65 pollutants. This criterion document is also
published in satisifaction of paragraph 11 of the Settlement Agreement
in Natural Resources Defense Council, et. al. vs. Train, 8 ERC 2120
(D.D.C. 1976), modified, 12 ERC 1833 (D.D.C. 1979).
The term "water quality criteria" is used in two sections of the
Clean Water Act, section 304 (a)(l) and section 303 (c)(2). The term has
a different program impact in each section. In section 304, the term
represents a non-regulatory, scientific assessment of ecological ef-
fects. The criteria presented in this publication are such scientific
assessments. Such water quality criteria associated with specific
stream uses when adopted as State water quality standards under section
303 become enforceable maximum acceptable levels of a pollutant in
ambient waters. The water quality criteria adopted in the State water
quality standards could have the same numerical limits as the criteria
developed under section 304. However, in many situations States may want
to adjust water quality criteria developed under section 304 to reflect
local environmental conditions and human exposure patterns before
incorporation into water quality standards. It is not until their
adoption as part of the State water quality standards that the criteria
become regulatory.
Guidelines to assist the States in the modification of criteria
presented in this document, in the development of water quality
standards, and in other water-related programs of this Agency, are being
developed by EPA.
STEVEN SCHATZOW
Deputy Assistant Administrator
Office of Water Regulations and Standards
111
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CRITERIA DOCUMENT
2,4-DICHLOROPHENOL
CRITERIA
Aquatic Life
The available data for 2,4-dichlorophenol indicate that acute and chron-
ic toxicity to freshwater aauatic life occur at concentrations as low as
2,020 and 365 ug/1, respectively, and would occur at lower concentrations
among species that are more sensitive than those tested. Mortality to early
life stages of one species of fish occurs at concentrations as low as 70
ug/1.
Only one test has been conducted with saltwater organisms and 2,4-di-
chlorophenol and no statement can be made concerning acute or chronic tox-
icity.
Human Health
For comparison purposes, two approaches were used to derive criterion
levels for 2,4-dichlorophenol. Based on available toxicity data, for the
protection of public health, the derived level is 3.09 mg/1. Using avail-
able organoleptic data, for controlling undesirable taste and odor Qualities
of ambient water, the estimated level is 0.3 ug/1. It should be recognized
that organoleptic data as a basis for establishing a water Quality criterion
have limitations and have no demonstrated relationship to potential adverse
human health effects.
VI
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TABLE OF CONTENTS
Criteria Summary
Introduction A-1
Aquatic Life Toxicology B-l
Introduction B-l
Effects B-2
Acute Toxicity B-2
Chronic Toxicity B-3
Plant Effects B-3
Residues B-4
Miscellaneous B-4
Summary B-5
Criterion B-5
References B-7
Mammalian Toxicology and Human Health Effects C-l
Exposure C-l
Ingestion from Water C-l
Ingestion from Food C-9
Inhalation C-16
Dermal C-16
Pharmacokinetics C-17
Absorption C-17
Distribution C-17
Metabolism C-17
Excretion C-19
Effects C-19
Acute, Subacute and Chronic Toxicity C-19
Synergism and/or Antagonism C-23
Teratogenicity C-24
Mutagenicity C-24
Carcinogenicity C-24
Other Effects C-29
Criterion Formulation C-31
Current Levels of Exposure C-31
Special Groups at Risk C-31
Basis and Derivation of Criterion C-31
References C-35
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ACKNOWLEDGEMENTS
Aquatic Life Toxicity:
William A. Brungs, ERL-Narragansett
U.S. Environmental Protection Agency
David J. Hansen, ERL-Gulf Breeze
U.S. Environmental Protection Agency
Mammalian Toxicology and Human Health Effects
Gary Osweiler (author)
University of Missouri
John F. Risher (doc. mgr.) ECAO-Cin
U.S. Environmental Protection Agency
Bonnie Smith (doc. mgr.) ECAO-Cin
U.S. Environmental Protection Agency
A. Wallace Hayes
University of Mississippi Medical Center
Steven D. Lutkenhoff, ECAO-Cin
U.S. Environmental Protection Agency
Jerry F. Stara, ECAO-Cin
U.S. Environmental Protection Agency
Philip J. Wirdzek, OWPS
U.S. Environmental Protection Agency
Herbert Cornish
University of Michigan
Patrick Durkin
Syracuse Research Corporation
Terence M. Grady, ECAO-Cin
U.S. Environmental Protection Agency
Van Kozak
University of Wisconsin
Herbert Schumacher
National Center for Toxicological Research
William W. Sutton, EMSL-LV
U.S. Environmental Protection Agency
Gunther Zweig, OPP
U.S. Environmental Protection Agency
Technical Support Services Staff: D.J. Reisman, M.A. Garlough, B.L. Zwayer,
P.A. Daunt, K.S. Edwards, T.A. Scandura, A.T. Pressley, C.A. Cooper,
M.M. Denessen.
Clerical Staff: C.A. Haynes, S.J. Faehr, L.A. Wade, D. Jones, B.J. Bordicks,
B.J. Quesnell, C. Russom, R. Rubinstein.
w
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INTRODUCTION
2,4-Dichlorophenol (2,4-DCP) is a commercially produced substituted
phenol used entirely in the manufacture of industrial and agricultural prod-
ucts. As an intermediate in the chemical industry, 2,4-DCP is utilized
principally as the feedstock for the manufacture of the herbicide, 2,4-di-
chlorophenoxyacetic acid (2,4-0), 2,4-0 derivatives (germicides, soil steri-
lants, etc.) and certain methyl compounds used in mothproofing, antiseptics,
and seed disinfectants. 2,4-DCP is also reacted with benzene sulfonyl chlo-
ride to produce miticides or further chlorinated to pentachlorophenol, a
wood preservative (U.S. EPA, 1975).
2,4-Dichlorophenol is a colorless, crystalline solid having the empiri-
cal formula C^ClgO, a molecular weight of 163.0 (Weast, 1975), a
density of 1.383 at 60°F/25*C and a vapor pressure of 1.0 mm Hg at 53.0°C
(Sax, 1975). The melting point of 2,4-DCP is 45°C, and the boiling point is
210"C at 760 mm Hg (Aly and Faust, 1965; Weast, 1975).
2,4-DCP is slightly soluble in water at neutral pH and dissolves readily
in ethanol and benzene (Kirk and Othmer, 1964). 2,4-DCP behaves as a weak
acid and is highly soluble in alkaline solutions, since it readily forms the
corresponding alkaline salt. The dissociation constant (pKj for 2,4-DCP
a
has been reported to be 7.48 (Pearce and Simpkins, 1968). Unlike the mono-
chlorophenols, 2,4-DCP is not volatile from aeneous alkaline solutions (Kirk
and Othmer, 1964).
2,4-DCP is readily prepared without benefit of a catalyst using gaseous
chlorine and molten phenol at 80 to 100'C. Synthesis is also attainable
through the chlorination of the monochlorophenols (Kirk and Othmer, 1972).
A-l
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It has been demonstrated that phenol is auite reactive to chlorine in
dilute aaueous solutions over a wide pH range (Carlson and Caple, 1975; Mid-
daugh and Davis, 1976).
Although 2,4-DCP presently has no direct commercial application, it is
used as an important chemical intermediate, and it is synthesized from
dilute aaueous solutions. Its identification as a metabolic intermediate
and degradation product of various commercial products by plants (Kirk and
Othmer, 1972), microorganisms (Kearney and Kaufman, 1972; Steenson and
Walker, 1957; Bell, 1957, 1960; Evans and Smith, 1954; Fernley and Evans,
1959; Loos, et al. 1967a,b; Loos, 1969) and sunlight (Aly and Faust, 1964;
Crosby and Tutass, 1966; Mitchell, 1961) has been well established.
Numerous studies on the microbial degradation of 2,4-DCP have been con-
ducted, revealing degradation to yield succinic acid (Alexander and Aleem,
1961; Macrae, et al. 1963; Paris and Lewis, 1973; Fernley and Evans, 1959;
Bell, 1957, 1960; Bollag, et al. 1968a,b; Macrae and Alexander, 1965; Chu
and Kirsch, 1972; Ingols, et al. 1966; Chapman, 1972; Duxbury, et al. 1970;
Loos, et al. 1967b; Tiedje, et al. 1969).
Few data exist regarding the persistence of 2,4-DCP in the environment.
2,4-DCP is slightly soluble in water, while its alkaline salts are readily
soluble in aaueous solutions. Its low vapor pressure and non-volatility
from alkaline solutions would cause it to be only slowly removed from sur-
face water via volatilization. Studies have indicated low sorption of
2,4-DCP from natural surface waters by various clays (Aly and Faust, 1964).
A-2
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REFERENCES
Alexander, M. and M.J.H. Aleem. 1961. Effect of chemical structure on
microbial decomposition of aromatic herbicides. Jour. Agric. Food Chem.
9: 44.
Aly, O.M. and S.D. Faust. 1964. Removal of 2,4-dichlorophenoxyacetic acid
and derivatives from natural waters. Jour. Am. Water Works Assoc. 57: 221.
Bell, G.R. 1957. Morphological and biochemical characteristics of a soil
bacterium which decomposes 2,4-dichlorophenoxyacetic acid. Can. Jour.
Microoiol. 3: 821.
Bell, G.R. 1960. Studies or a soil Achromobacter which degrades 2,4-di-
chlorophenoxyacetic acid. Can. Jour. Microdiol. 6: 325.
Bollag, J.M., et al. 1968a. 2,4-0 metabolism: Enzymatic hydroxylation of
chlorinated phenols. Jour. Agric. Food Chem. 16: 826.
Bollag, J.M., et al. 1968b. Enzymatic degradation of cnlorocatechols.
Jour. Agric. Food Chem. 16: 829.
Carlson, R.M. and R. Caple. 1975. Organo-chemical Implications of Water of
Water Chlorination. Iji: Proc. Conf. Environ. Impact Water Chlorination.
p. 73.
A-3
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Chapman, P.J. 1972. An Outline of Reaction Sequences Used for the Bacteri-
al Degradation of Phenolic Compounds. In: Degradation of Synthetic Organic
Molecules in the Biosphere. Proc. Conf. Natl. Acao. Sci., Washington, D.C.
p. 17.
Chu, J.P. and E.J. Kirsch. 1972. Metabolism of PCP by axenic bacterial
culture. Appl. Microbiol. 23: 1033.
Crosby, O.G. and H.O. Tutass. 1966. Photodecomposition of 2,4-dichloro-
phenoxyacetic acid. Jour. Agric. Food Chem. 14: 596.
Duxbury, J.M., et al, 1970. 2,4-D metabolism: enzmatic conversion of chlo-
romaleylacetic acid to succinic acid. Agric. Food. Chem. 18: 199.
Evans, W.C. and B. Smith. 1954. The photochemical inactivation and micro-
bial metabolism of the chlorophenoxyacetic acid heroicides. Proc. Biochem.
Soc. 571.
Fernley, H.N. and W.C. Evans. 1959. Metaoolism of 2,4-dichlorophenoxy-
acetic acid by soil pseudomonas. Proc. Biochem. Soc. 73: 228.
Ingols, R.S., et al. 1966. Biological activity of halophenols. Jour.
Water Pollut. Control Fed. 38: 629.
Kearney, P.C. and D.N. Kaufman. 1972. Microoial Degradation of Some Chlo-
rinated Pesticides. In: Degradation of Synthetic Organic Molecules in the
Biosphere. Proc. Conf. Natl. Acad. Sci., Washington, D.C. p.166.
A-4
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Kirk, R.E. ana D.F. Othmer. 1964. Kirk-Othmer Encyclopedia of Cnemical
Technology. 2nd ed. Interscience Publishers, New York.
Kirk, R.E. and D.F. Othmer. 1972. Kirk-Othmer Encyclopedia of Chemical
Technology. 3rd ed. Interscience Publishers, New York.
Loos, M.A. 1969. Phenoxyalkanoic Acids. Part I. _In_: P.C. Kearney and
D.D. Kaufman (eds.), Degradation of Herbicides. Marcel Dekker, New York.
Loos, M.A., et al. 1967a. Formation of 2,4-dichlorophenol and 2,4-di-
chloroanisole from 2,4-0 by Arthrobacter sp. Can. Jour. Microbiol. 13: 691.
Loos, M.H., et al. 1967b. Phenoxyacetate herbicide detoxication by bacte-
rial enzymes. Jour. Agric. Food. Chem. 15: 858.
Macrae, I.C. and M. Alexander. 1965. Microoial degradation of selected
pesticides in soil. Jour. Agric. Food Chem. 13: 72.
Macrae, I.C., et al. 1963. The decomposition of 4-(2,4-dichlorophenoxy-
butyric) acid by Flavobacterium sp. Jour. Gen. Microbiol. 32: 69.
Midaaugh, D.P. and W.P. Davis. 1976. Impact of Chlorination Processes on
Marine Ecosystems. In: Water Quality Criteria Research of the U.S. Environ.
Prot. Agency. EPA Report No. 600/3/-76-079. Presented at 26th Annu. Meet.
Am. Inst. Biol. Sci., August 1975.
A-5
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Mitchell, L.C. 1961. The effect of ultraviolet light (2537A) on 141 pesti-
cide chemicals by paper chromatography. Jour. Off. Analyt. Chem. 44: 643.
Paris, D.F. and D.L. Lewis. 1973. Chemical and microbial degradation of 10
selected pesticides in aquatic systems. Residur Rev. 45: 95.
Pearce, P.J. and R.J.J. Simpkins. 1968. Acid strengths of some picric
acids. Can. Jour. Chem. 46: 241.
Sax, N.I. 1975. Dangerous properties of industrial materials. 4th ed.
Van Nostrand Rheinold Co., New York.
Steenson, T.I. and N. Walker. 1957. The pathway of breakdown of 2,4-di-
chloro- and 4-chloro-2-methyphenoxyacetate by bacteria. Jour. Gen. Micro-
biol. 16: 146.
Tiedje, J. M., et al. 1969. 2,4-D metabolism: pathway of degradation of
chlorocatechols by Arthrobacter sp. Jour. Agric. Food Chem. 17: 1021.
U.S. EPA. 1975. Significant organic products and organic chemical manufac-
turing. Washington, O.C.
Weast, R.D., (ed.) 1975. Handbook of Chemistry and Physics. 55th ed. CRC
Press, Cleveland, Ohio.
A-6
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Aquatic Life Toxicology*
INTRODUCTION
2,4-Dichlorophenol has been widely used as a chemical intermediate in
the manufacture of herbicides, germicides, temporary soil sterilants, plant
growth regulators, mothproofing agents, seed disinfectants, miticides, and
wood preservatives. In spite of this, there are only limited toxicity data
available dealing with effects of 2,4-dichlorophenol on freshwater aquatic
organisms. Flavor-impairment studies with 2,4-dichlorophenol showed that
flesh tainting in fish occurred at substantially lower concentrations than
those that produced other adverse effects on plant, fish, and invertebrate
species. For this reason, flavor-impairment information may be an important
consideration in deriving the 2,4-dichlorophenol criterion for freshwater
aquatic organisms. Additional testing of 2,4-dichlorophenol is necessary to
meet the minimum data base requirement, detailed in the guidelines, for the
derivation of a criterion. This testing should verify if flavor-impairment
of fish flesh is, indeed, the most sensitive and important parameter for
protecting the presence of and the uses of freshwater aquatic organisms.
Only one test has been conducted with 2,4-dichlorophenol and saltwater
organisms.
*The reader is referred to the Guidelines for Deriving Water Quality Cri-
teria for the Protection of Aquatic Life and Its Uses in order to better
understand the following discussion and recommendation. The following
tables contain the appropriate data that were found in the literature, and
at the bottom of each table are calculations for deriving various measures
of toxicity as described in the Guidelines.
B-l
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EFFECTS
Acute Toxicity
The data base for freshwater invertebrate species (Table 1) consists of
two static tests on a single cladoceran species. The 48-hour LCgQ values
determined for Daphnia magna by Kopperman, et al. (1974) and U.S. EPA (1978)
were 2,610 wg/l and 2,600 u9/l, respectively. The LC5Q values from both
tests show good reproducibility of results between investigators. Since all
the invertebrate acute data available for 2,4-dichlorophenol are for only
one species, it is impossible to determine the relative sensitivity of Daph-
nia magna with that of other invertebrate species.
Only two acute values dealing with 2,4-dichlorophenol effects on fresh-
water fish species were available (Table 1) and only one of these tests was
conducted using flow-through conditions and measured concentrations.
Phipps, et al. (Manuscript) calculated a 96-hour LC50 of 8,230 ug/l for
fathead minnows. This is more than 4 times higher than the 96-hour LCcQ
of 2,020 ug/1 for bluegills determined under static test conditions using
nominal concentrations (U.S. EPA, 1978). Although differences in test meth-
ods make comparisons difficult, it appears bluegills may be slightly more
sensitive to 2,4-dichlorophenol than are fathead minnows.
The LCgg values for Daphnia magna fall between the LCgQ values found
for bluegills and fathead minnows. From the few acute data available, it
appears that there are no large differences in the sensitivity of fish and
invertebrate species to 2,4-dichlorophenol.
The 96-hour LC5Q values for chlorinated phenols and bluegills (U.S.
EPA, 1978) in this and other criterion documents are directly related to the
degree of chlorination. These values decrease from 6,590 ug/1 for 2-chloro-
phenol and 3,830 wg/l for 4-chlorophenol to 60 and 70 yg/1 for pentachlo-
B-2
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rophenol. Data for other species do not correlate as well.
Chronic Toxicity
The freshwater chronic data base for 2,4-dichlorophenol consists of a
single embryo-larval test (Holcombe, et al. Manuscript) conducted with fat-
head minnows. The chronic limits determined from this study (290-460 pg/1)
were based on effects on larval survival, and the resulting chronic value
was 365 ug/l (Table 2).
There appears to be a moderate difference between the concentration of
2,4-dichlorophenol that cause acute and chronic effects on fathead minnows.
The acute-chronic ratio for this species is 23 (Table 2).
Data from an embryo exposure and an additional 4-day larval exposure
with three species of fishes at two water hardnesses (Birge, et al. 1979)
will be discussed in the miscellaneous section.
Species mean acute and chronic values for 2,4-dichlorophenol are listed
in Table 3.
Plant Effects
The toxicity of 2,4-dichlorophenol to freshwater aquatic plants does not
appear important in the derivation of a criterion since deleterious on
plants (Table 4) occurred only at much higher concentrations than those
which produced acute toxic effects on fish and invertebrate species. How-
ever, the knowledge that 2,4-dichlorophenol is not highly toxic to plants is
important because 2,4-dichlorophenol is used in producing the commonly used
herbicide, 2,4-D (2,4-dichlorophenoxyacetic acid). Some observed toxic ef-
fects of 2,4-dichlorophenol on plants were the complete destruction of chlo-
rophyll in Chlorella pyrenoidosa at 100,000 Mg/l (Huang and Gloyna, 1968)
and a 50 percent reduction in chlorophyll in Lemna minor at 58,320 wg/1
(Blackman, et al. 1955). Huang and Gloyna (1968) also determined that there
B-3
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was a 56.4 percent reduction of photosynthetic oxygen production in Chlor-
ella pyrenoidosa after exposure to 50,000 ug/1 for 120 minutes.
Residues
No measured steady-state bioconcentration factor (BCF) is available for
2,4-d i ch1oropheno1.
Miscellaneous
Birge, et al. (1979) determined LC^Q values for three fish species
after embryo exposures and after additional 4-day larval exposures at hard-
nesses of 50 and 200 mg/1 as CaC03 (Table 5). The LC50 values after the
4-day larval exposures were 80 and 70 ug/1 for rainbow trout, 390 and 260
ug/1 for goldfish, and 1,350 and 1,070 pg/1 for channel catfish at hard-
nesses does not substantially affect toxicity, although for all species
tested the LC^Q values for 2,4-dichlorophenol were slightly higher at low
hardness than at high hardness. The LCcn value of 260 ug/1 for goldfish
(Birge, et al. 1979), which was based on an 8-hour total exposure of embryos
and larvae, was considered to be the lowest freshwater acute value for
2,4-dichlorophenol. Rainbow trout embryos and larvae exposed in this study
were fathead minnows since the chronic value for fatheads is 365 ug/1
(Holcombe, et al. Manuscript). Since the rainbow trout LCgQ of 70 ug/1
(Birge, et al. 1979) was based on a relatively long-term study (24-day em-
bryo exposure plus a 4-day larval exposure), this value was considered to be
the lowest chronic value.
Flavor-impairment studies (Shumway and Palensky, 1973) showed that flesh
tainting occurred when 2,4-dichlorophenol concentrations ranging from 0.4
ug/1 to 14 ug/l» depending on the species of fish tested, were exceeded
(Table 5). Based on the available data for 2,4-dichlorophenol, flavor-
impairment in fish occurs at lower concentrations than other effects used to
B-4
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evaluate toxicity and may be an important consideration in deriving a cri-
terion. Since the purpose of the Guidelines is to set water quality cri-
teria which protect both the presence and uses of aquatic life, a criterion
which will protect against tainting of fish flesh is necessary to preserve
the quality of the freshwater fishery. However, the lack of toxicity data
for 2,4-dichlorophenol makes it impossible to ascertain if a criterion based
on flavor-impairment of fish flesh would be low enough to protect all fresh-
water aquatic organisms.
The only saltwater data available on the effects of 2,4-dichlorophenol
are from an acute exposure to mountain bass, a species endemic in Hawaii
(Hiatt, et al. 1953). Abnormal behavioral responses, including rapid swim-
ming in a vertical position, gulping at the surface of the water, and jerky
motions, were observed in a nominal concentration of 20,000 pg/1.
Summary
Acute effects on freshwater fish and invertebrate species were observed
at concentrations from 260 to 8,230 pg/1. The chronic value for the fathead
minnow was 365 ug/1 with an acute-chronic ratio of 23. An embryo and 4-day
larval exposure of rainbow trout yielded an LC^Q value of 70 yg/1. The
lowest plant effect (50,000 gg/1) caused by exposure to 2,4-dichlorophenol
was based on a reduction in photosynthetic oxygen production in an algal
species. Effects on flavor-impairment of largemouth bass occurred when con-
centrations of 2,4-dichlorophenol exceeded 0.4 yg/1.
CRITERIA
The available data for 2,4-dichlorophenol indicate that acute and
chronic toxicity to freshwater aquatic life occur at concentrations as low
as 2,020 and 365 yg/1, respectively, and would occur at lower concentrations
among species that are more sensitive than those tested. Mortality to early
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life stages of one species of fish occurs at concentrations as low as 70
u9/1.
Only one test has been conducted with saltwater organisms and 2,4-di-
chlorophenol, and no statement can be made concerning acute or chronic
toxicity.
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Table 1. Acute values for 2,4-dlchlorophenol
LC50/EC50
Species Method* (fig/I)
Species Mean
Acute Value
(Ug/l) Reference
FRESHWATER SPECIES
Cladoceron, S, U 2,610
Daphnla magnn
Cladoceran, S, U 2,600
Oaphnla magna
Fathead minnow (juvenile), FT, M 8,230
Plmephales prone las
BluegHI, S, U 2,020
Lepomls macrochlrus
Kopperman, et al.
1974
2,605 U.S. EPA, 1978
6,230 Phlpps, et al.
Manuscript
2,020 U.S. EPA, 1978
* S B static, FT = flow-through, U c unmeasured, M » measured
No Final Acute Values are calculable since the mini mum data base requirements are not met.
B-7
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Table 2. Chronic valu*s for 2.4-dlchloropnwtol (Holcoatw, «t al. Manuscript)
Sp«cU
Fathead minnow,
Plmephales prcreelas
LlMltS
Method* (iig/J)
FRESHWATER SPECIES
ELS
290-460
M»an
Chronic ValiM
(Hfl/0
J65
ELS - early life stage
Acute-Chronic Ratio
Chronic Acute
Value Value
(ug/l) (U9/D
Fathead minnow,
Plreephales proroelas
365
8,230
Ratio
23
B-8
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Table 3. Species Mean acute and chronic values for 2,4-dichlorophenol
Specie* Mean Species Mean
Acute Value* Chronic Value Acute-Chronic
Number Specie* (ua/l) (yg/1) Ratio**
3
2
1
FRESHWATER SPECIES
Fathead minnow, 8,230 365
Plmephales prone las
Cladoceran, 2,605
Daphnla magna
Blueglll, 2,020
Lepomls macrochlrus
23
-
-
* Rank from high concentration to low concentration by species mean acute value.
**See the Guidelines for derivation of this ratio.
B-9
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Table 4. Plant values for 2.4-dlchlorophenol
Result
Species Effect (pg/l) Reference
FRESHWATER SPECIES
Alga, Complete 100,000 Huang & Gloyna,
Chloreda pyrenoldosa destruction of 1968
chlorophy11
Alga, 56.4$ reduction 50,000 Huang & Gloyna,
Chloral la pyrenoldosa of photosynthetlc 1968
oxygen production
Duckweed, 50* reduction 58,320 Blackman, et al.
Lemna minor In chlorophyll 1955
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Table 5. Other data for 2,4-dlctilorophwtol
Species
Duration
Effect
FRESHWATER SPECIES
Lymnaeld snails,
Pseudosucclnea columella
Fossarla cubensls
Crayfish,
Orconectes proplnquus
Orconectes inmunls
Cambarus robustus
Crayfish,
Orconectes proplnquus
Orconectes Imnunls
Cambarus robustus
Crayfish,
Orconectes proplnquus
Orconectes inmunls
Cambarus robustus
Crayfish,
Orconectes proplnquus
Orconectes inmunls
Cambarus robustus
Rainbow trout,
Sal mo galrdneri
Rainbow trout,
Sal mo galrdnerl
Rainbow trout,
Sal mo galrdnerl
Rainbow trout.
Sal mo galrdnerl
Rainbow trout.
Sal mo galrdneri
24 hrs
48 hrs
1 wk
10 days
10 days
48 hrs
24-day embryo
exposure
24-day embryo
exposure
24-day embryo
plus 4-day
larval exposure
24-day embryo
plus 4-day
100* mortality
100J mortality
1009 mortality
14 % mortality
Increased blood
glucose levels
ETC"
LC50 at hardness
of 50 mg/l CaC03
LC50 at hardness
of 200 mg/l CaC03
LC50 at hardness
of 50 mg/l CaC03
LC50 at hardness
of 200 mg/l CaC03
Result
(ug/D
10,000
10,000
5,000
1,000
1,000
1
80
70
80
70
Reference
Batte & Swanson,
1952
Tel ford, \974
Tel ford, 1974
Tel ford, 1974
Tel ford, 1974
Shumway & Palensky,
1973
Birge, at al. 1979
Blrge, et al. 1979
Blrge, et al. 1979
Blrge, et al. 1979
larval exposure
B-ll
-------
Tab I* 5. (Continued)
Species
Goldfish,
Cnrnsslus nuratus
Goldfish,
Carasslus aurntus
Goldfish,
Carasslus aurntus
Goldfish,
Carass I us auratus
Goldfish,
Carass Ius auratus
Fathead minnow
(juvenila),
Plmepholes promelas
Channel catfish,
Ictalurus punctatus
Channel catfish
Ictalurus punctatus
Channel catfish,
Ictalurus punctatus
Channel catfish,
Ictalurus punctatus
Blueglll,
Lepomls macrochlrus
Largemouth bass,
Mlcropterus SB I moIdes
Duration
4-day embryo
exposure
4-day embryo
exposure
4-day embryo
plus 4-day
larval exposure
4-day embryo
plus 4-day
larval exposure
24 hrs
192 hrs
4-day embryo
exposure
4-day embryo
exposure
4-day embryo
plus 4-day
larval exposure
4-day embryo
plus 4-day
larval exposure
48 hrs
48 hrs
Effect
LC50 at hardness
of 50 mg/I CaCOj
LC30 at hardness
of 200 mg/I CaC03
LC50 at hardness
of 50 ing/1 CaC03
LC50 at hardness
of 200 mg/I CaC03
LC50
LC50
LC50 at hardness
of 50 mg/l CaC03
LC50 at hardness
of 200 mg/l CaC03
LC50 at hardness
of 30 ng/l CaC03
LC50 at hardness
Of 200 mg/l CaC03
ETC*
ETC*
Result
(ua/l) Reference
1,760 Blrge, et at. 1979
1,240 Blrge, et al. 1979
390 Blrge, et a I. 1979
260 Blrge, et al. 1979
7,600 Kobayashl, et al.
1979
6,500 Phlpps, et al.
Manuscript
1,850 Blrge, et al. 1979
1,700 Blrge, et al. 1979
1,350 Blrge, et al. 1979
1,070 Blrge. et al. 1979
14 Shumway & Palensky,
1973
0.4 Shumway & Palensky,
1973
B-12
-------
Table 5. (Continued)
Result
Species Duration Effect ((ig/l) Reference
SALTWATER SPECIES
Mountain bass** Acute Moderate 20,000 Hlatt, et a I. 1953
Kuhlla sandvIcons 15 response reaction
* ETC = the highest estimated concentration of material that will not Impair the flavor of the
flesh of exposed fish.
••Endemic In Hawaii
B-13
-------
REFERENCES
Batte, E.G. and L.E. Swanson. 1952. Laboratory evaluation of organic com-
pounds as molluscicides and ovicides. II. Jour. Parasitol. 38 65.
Birge, W. J., et al. 1979. Toxicity of organic chemicals to embryo-larval
stages of fish. EPA-560/11-79-007. U.S. Environ. Prot. Agency.
Blackman, G.E., et al. 1955. The physiolgical activity of substituted
phenols. I. Relationships between chemical structure and physiological
activity. Arch. Biochem. Biophys. 54: 45.
Hiatt, R.W., et al. 1953. Effects of chemicals on a schooling fish, Kuhlia
sandvicensis. Biol. Bull. 104: 28
Holcombe, G.W., et al. Effects of phenol, 2,4-dimethylphenol, 2,4-dichlo-
rolphenol, and pentachlorophenol on embryo, larval, and early-juvenile fat-
head minnows (Pimephales promelas). (Manuscript)
Huang, J. and E.F. Gloyna. 1968. Effect of organic compounds on photo-
synthetic oxygenation. I. Chlorophyll destruction and suppression of pho-
tosynthetic oxygen production. Water Res. 2: 347.
Kobayashio, K., et al. 1979. Relation between toxicity and accumulation of
various chlorophenols in goldfish. Bull. Jap. Soc. Sci. Fish. 45: 173.
B-14
-------
Kopperman, H.L., et al. 1974. Aaueous chlorination and ozonation studies.
I. Structure-toxicity correlations of phenolic compounds to Daphnia magna.
Chem. Biol. Interact. 9: 245.
Phipps, G.L., et al. The acute toxicity of phenol and substituted phenols
to the fathead minnow. (Manuscript)
Shumway, D.L. and J.R. Palensky. 1973. Impairment of the flavor of fish by
water pollutants. EPA-R3-73-010. U.S. Environ. Prot. Agency.
Telford, M. 1974. Blood glucose in crayfish. II. Variations induced by
artificial stress. Comp. Biochem. Physiol. 48A: 555.
U.S. EPA. 1978. In-depth studies on health and environmental impacts of
selected water pollutants. Contract No. 68-01-4646. U.S. Environ. Prot.
Agency.
B-15
-------
Mammalian Toxicology and Human Health Effects
EXPOSURE
Ingestion from Water
Absorption of 2,4-dichlorophenol (herein referred to as 2,4-
DCP in this document) by biological tissues may occur upon exposure
to 2,4-DCP either dissolved in water or associated with suspended
matter or sediments in water. Chlorophenols such as 2,4-DCP are
weak acids that become increasingly ionized under alkaline condi-
tions; they are mainly non-ionized at physiological pH. These pro-
perties, together with the lipophilic nature of chlorophenols (in-
cluding 2,4-DCP), make it likely that chlorophenols would be ab-
sorbed from the gastrointestinal tract.
Sources of 2,4-DCP in water may be diffuse (e.g., agricultural
runoff) or localized (e.g., point source pollution from manufactur-
ing waste discharges). Sidwell (1971) verified the presence of
2,4-DCP in 2,4-dichlorophenoxyacetic acid (2,4-D) manufacturing
wastes. Over a 7-month period, total chlorophenol content ranged
from 68 mg/1 of waste to a high of 125 mg/1, with 2,4-DCP content
ranging as high as 89 percent of the total. Details of these find-
ings are presented in Table 1.
If certain assumptions are made, the data of Sidwell (1971)
can be used to estimate human exposure to 2,4-DCP from drinking
water obtained below a point source of this type. Assuming (1) an
effluent with a 2,4-DCP concentration of 125 mg/1 in water contain-
ing 100,000 mg/1 of total solids (Table 1), (2) dilution in the
watercourse occurring to the point where an acceptable freshwater
total solids concentration of 1,000 mg/1 is reached, and (3) no
removal of 2,4-DCP by water treatment, drinking water will contain
C-l
-------
TABLE 1
Industrial Plant Effluent Content of Chlorophenols'
Date Sampled
Total Solids (mg/1)
Temperature {°C)
PH
Chlorophenols (mg/1)
Phenol Type (%)b
Phenol-
2-chloro-
2,4-dichloro-
2,6-dichloro-
2,5-dichloro-
4-chloro-
2,4,6-tr ichloro-
2,4 , 5-tr ichloro-
25 Jan
6,960
12
7.5
68
3.4
2.9
73.6
9.9
trace
2.5
2.8
4.7
3 Mar
40,100
18
7.6
118
6.2
6.1
17.9
41.7
6.2
12.1
9.9
trace
21 Apr
76,320
21
7.4
125
1.7
trace
20.0
38.8
1.7
18.3
19.5
trace
28 May
104,860
28.5
7.4
112
24.8
trace
11.4
30.5
trace
20.0
13.3
trace
27 Aug
11,000
24
7.0
74
trace
trace
89.0
3.0
1.8
2.8
3.4
trace
Modified from Sidwell, 1971
Percent of total phenols present
02
-------
2,4-DCP at an estimated concentration of 1.25 mg/1. If the daily
water intake of a 70 kg person is assumed to be 2 liters, this would
result in a daily 2,4-DCP dosage of 0.036 mq/kg body weight/day.
It should be emphasized that this dosage is a worst case exposure
level that would probably occur only in drinking water obtained
below a 2,4-DCP-contaminated point source discharge.
Sharpee (1973) noted the presence of 2,4-DCP in soil treated
with 2,4-dichlorophenoxyacetic acid (2,4-D). This presence may be
accounted for by the photolytic or microbial breakdown of 2,4-D
which will be discussed later in this document. Walker (1961)
studied the contamination of ground water by the migration of waste
products from the manufacture of chemicals at the Rocky Mountain
Arsenal, Denver, Colorado. Walker reported the phytotoxic proper-
ties of water caused by either 2,4-D or an unnamed "closely related
compound." The 2,4-D type compounds were not a direct product of
the Arsenal operations, but rather were apparently the result of
chemical reactions which occurred within basins used for the stor-
age of effluents from a variety of Arsenal operations.
If diffuse or point source contamination of waters with 2,4-
DCP is in fact occurring, the dissipation of this compound in
aquatic environments becomes an important consideration. The major
avenues of 2,4-DCP dissipation that have been studied are microbial
degradation and photodecomposition. Aly and Faust (1964) examined
the dissipation of 2,4-DCP from natural lake waters at a buffered
pH of 7. In aerated lake waters, with initial 2,4-DCP concentra-
tions of 100, 500, and 1,000 pg/1, the percentages of 2,4-DCP re-
maining at 9 days were 0, 0.34, and 46 respectively. By contrast,
initial concentrations of 100, 500, and 1,000 yg/1 in unaerated and
C-3
-------
unbuffered waters resulted in percentages of 40, 51.6, and 56,
respectively, remaining at 17 days. Aly and Faust concluded that
the persistence of chlorophenol would tend to increase at lower pH
and under anaerobic conditions that might result from the decompo-
sition of excessive organic matter.
Ingols, et al. (1966) studied the degradation of various chlo-
rophenols by activated sewage sludge and concluded that 2,4-DCP was
degraded more rapidly by activated systems with previous exposure
to chlorophenols than by those with no previous exposure to chloro-
phenols. when activated sludge was exposed to 2,4-DCP at levels of
100 mg/1 of sludge/ 75 percent of the chemical disappeared in two
days, and essentially 100 percent was gone in five days. Hemmett
(1972) showed that microorganisms acclimated to the herbicide 2,4-D
could degrade 2,4-DCP without a lag period, implying similar bio-
logical pathways for the two compounds.
When 2,4-DCP was subjected to aeration basin treatment, the
initial concentration of 64 mg/1 dropped to an undetectable level
within five days (Sidwell, 1971); this was more rapid than the rate
of degradation observed for 2,4-DCP in distilled water. When an
aerated lagoon alone was used, removal of all chlorophenols varied
from 55 to 89 percent. Overall, removal using both lagoon and sta-
bilization ponds ranged from 87 to 94 percent. Thus, natural
degradation of 2,4-dichlorophenol may be enhanced by proper appli-
cation of effluent waste management principles.
Dissipation of dichlorophenols also occurs through photode-
composition in aqueous solutions. Aly and Faust (1964) demonstrat-
ed that (1) 2,4-DCP was decomposed by ultraviolet light, and
C-4
-------
(2) the rate of photolysis in distilled water decreased as pH de-
creased. Degradation of 50 percent of 2,4-DCP by ultraviolet light
was accomplished in two minutes at pH 9.0, in five minutes at pH
7.0, and in 34 minutes at pH 4.0. The studies of Aly and Faust were
conducted with light of wavelength 253.7 nm, which is slightly
shorter than the natural ultraviolet radiation wavelength range of
292 to 400 nm.
The riboflavin-sensitized dimerization of 2,4-dichlorophenol
to tetrachlorodiphenyl ethers, tetrachlorodihydroxy-biphenyls, and
other products was reported by Plimmer and Klingebiel (1971).
Chlorinated dibenzo-p-dioxins, which could have resulted from ring
closure of these tetrachlorodiphenyl ethers, were not detected in
the products of photolysis. The authors speculated that failure to
detect chlorinated dibenzo-p-dioxins may have been due to the rapid
photolytic breakdown of those dioxins. Rapid photolysis of chlori-
nated dibenzo-p-dioxins was confirmed by Crosby, et al. (1971).
That 2,4-dichlorophenol can be formed as a photolytic product
of the herbicides 2,4-D and nitrofen (2,4-dichlorophenyl p-nitro-
phenyl ether) in aqueous suspension under sunlight or simulated
sunlight, has been noted by several investigators, including Aly
and Faust (1964), Zepp, et al. (1975) , and Nakagawa and Crosby
(1974a,b). Crosby and Tutass (1966) irradiated 2,4-0 with artifi-
cial light (254 nm) and natural sunlight and observed that under
both conditions 2,4-dichlorophenol was formed as a photolytic prod-
uct of 2,4-D and was further degraded to 4-chlorocatechol. 2,4-DCP
was photolabile, with 50 percent being lost in five minutes at
pH 7.0.
C-5
-------
Microbial decomposition of 2 ,4-dichlorophenol in soils and
aauatic environments has been extensively studied. Alexander and
A^eem (1961) found that when 80 yg 2,4-DCP/ml medium was incubated
in the presence of Dunkirk silt loam and Mardin silt loam, 2,4-DCP
was not detectable after nine and five days, respectively. When
these soil preparations were treated with sodium azide, no disap-
pearance of 2,4-DCP was noted, supporting the role of microbiologi-
cal processes in the degradation. Loos, et al. (1967) found that
extracts of Arthrobacter sp. contained enzymes capable of dehalo-
genating 2,4-dichlorophenol. Degradation was rapid, with 100 per-
cent chloride release from 2,4-DCP occurring after four hours of
incubation. The cells responsible for the dehalogenating process
were active when cultured on the herbicides 2,4-D or 2-methyl-4-
chlorophenoxyacetate (MCPA). Kearney, et al. (1972) found no
tetrachlorodibenzo-p-dioxin in soils treated with up to 1,000 ug
2,4-DCP/g. Sharpee (1973) measured 2,4-DCP present in the soil as
a consequence of 2,4-D application and found that 2,4-DCP did
appear in soil treated with 2,4-D, but it did not persist as long as
the 2,4-D.
As indicated earlier, the principal source of 2,4-dichloro-
phenol in soils is believed to be the herbicide 2,4-D. The various
intermediates (including 2,4-DCP) in the microbial metabolism of
2,4-D have been characterized by several investigators (Spokes and
Walker, 1974; Loos, et al., 1967; Bollag, et al., 1968; Evans, et
al., 1971; Paris and Lewis, 1973; Ingols, et al., 1966; Alexander
and Aleem, 1961). Kearney and Kaufman (1972) have shown that the
organisms capable of degrading 2,4-D to 2,4-DCP continue the degra-
-------
dation process to catechol intermediates and finally to succinic
acid. Thus, the herbicide 2,4-D is eventually biodegraded to an
ecologically acceptable product, succinic acid.
Recently, attention has focused on a potential chlorophenol
source of a more ubiquitous nature than herbicide and pesticide
applications. Both municipal and industrial wastewater are often
subjected to chlorination to achieve disinfection and deodorization
(Barnhart and Campbell, 1972) . One result of chlorination is the
reaction of chlorine with phenol to produce chlorophenols, some of
which are a source of obnoxious odors and/or taste (Dietz and
Traud, 1978; Barnhart and Campbell, 1972; Burttschell, et al.
1959; Hoak, 1957).
Phenol has been observed to be quite reactive with chlorine in
dilute aqueous solutions. This high reactivity of phenol is at-
tributed to the ring-activating, electron-releasing properties of
the -OH functional group (Barnhart and Campbell, 1972; Morris,
1978). Halogen substitution is favored in the ortho- and para-
positions (Burttschell, et al. 1959).
Chlorination of phenols results in a stepwise substitution of
the 2, 4, and 6 positions of the aromatic ring. Barnhart and Camp-
bell (1972) felt that it was probable that chlorination resulted in
a complex mixture of chlorophenols. Burttschell, et al. (1959)
chlorinated 1 liter of 20 mg phenol/ml solution containing 2 g/1
sodium bicarbonate with 40 mg chlorine and isolated 2,4-DCP as one
of three major chlorophenols. Relative chlorophenol content deter-
mined in this study was as follows:
C-7
-------
Component Percent of Product
Phenol 1-2
2-Chlorophenol 2-5
4-Chlorophenol 2-5
2,4-Dichlorophenol 20
2,6-Dichlorophenol 25
2,4,6-Trichlorophenol 40-50
(Absolute amounts of chlorophenols were not reported.)
Lee and Morris (1962) verified the stepwise chlorination of
phenol to chlorophenolic compounds. Furthermore, they determined
that the reaction rate and yield of 2,4-DCP is quite pH dependent,
with a decrease in generation time and an increase in yield for
2,4-DCP as pH increases from 7 to 9. The reactions occurred at ini-
tial chlorine concentrations of 1 ug/g and phenol concentrations of
50 ng/g.
Jolley (1973) indicated that development of chlorinated organ-
ics, including chlorinated phenols, is retarded in solutions with
high ammonia concentrations. In a later study, Jolley, et al.
(1978) examined the chlorination of sewage waters under conditions
simulating those used for disinfection of sewage effluents and/or
antifoulant treatment of cooling waters of electric power generat-
ing plants. Over 50 chloro-organic constituents were separated in
each analysis of concentrated sewage effluent chlorinated in the
laboratory with 2.5 to 6 mg/1 concentrations of chlorine. Similar
studies were also done on two bodies of lake water, each receiving
effluent from a coal-fired, electric-power generating plant. Tn
the three systems examined, Jolley, et al. (1978) detected mono-
chlorophenols at ng/g levels but found no dichlorophenols.
C-8
-------
Glaze, et al. (1978) identified trichlorophenols, but found no
dichlorophenols, in superchlorinated municipal wastewaters. Thus,
in contrast to laboratory demonstrations of DCP formation, recent
work under conditions simulating the natural environment has not
established that 2,4-DCP is a significant product resulting from
chlorination of phenol-containing waters.
Ingestion from Food
Any 2,4-dichlorophenol contamination of food products (non-
aquatic) would probably result from use of the herbicide 2,4-D. As
stated earlier, 2,4-DCP is a possible contaminant of 2,4-D, as well
as an intermediate compound in the biological and ohotolytic degra-
dations of 2,4-D.
Absorption of 2,4-DCP has been reported for some plant species
(Isensee and Jones, 1971). Total DCP content in oat and soybean
plants increased for approximately three weeks when the soil con-
tained a DCP concentration of 0.07 ug/g. As these plants grew, the
total tissue content of DCP remained relatively constant but de-
creased as the plants matured. At the time of harvest, oats con-
tained 0.01 yg of DCP per gram of plant tissue, and soybeans con-
tained 0.02 yg/g. The 2,4-DCP did not seem to concentrate in the
plant seeds. DCP was not detected in the grain of these oat plants,
and the soybean seeds contained only 1 to 2 percent of the total
plant DCP. No evidence was found of DCP translocation in soybeans
after foliar application.
The conversion of 2,4-D to 2,4-DCP has been demonstrated in
sunflowers, corn, barley, strawberries, and kidney beans. Steen,
et al. (1974) found that 2,4-DCP residues in plants treated with
-------
2,4-D herbicide were from 20 to 100 times lower than residues of
2,4-D. Related studies by Sokolov, et al. (1974) involved applica-
tion of 2,4-D to rice fields. At harvest, rice grain contained
neither 2,4-D nor 2,4-DCP, even though 2,4-DCP was present in the
rice plant. The 2,4-DCP content in potato tubers treated with
2,4-D amounted to less than 10 percent of the total 2,4-D content.
There is little information on the transfer of 2,4-D or its
degradation compounds to food products of animal origin. Mitchell,
et al. (1946) provided evidence for the gastrointestinal absorption
of 2,4-D in lactating dairy cows and detected the herbicide in
blood serum during a 106-day oral dosing study. However, 2,4-D was
not detected in the milk. More recently, 2,4-D was not found
(detection limit 0.1 ug/g) in bovine milk following oral doses of 5
ug 4-(2,4-dichlorophenoxybutyric) acid [4-(2,4-DB}] (Gutenmann, et
al. 1963a) or 2,4-D (Hutenmann, et al. 1963b) or 50 ug 2,4-n
(Bache, et al. 1964a) per gram of feed.
Clark, et al. (1975) studied the tissue distribution of 2,4-
DCP in sheep and cattle fed 2,4-D at the relatively high concen-
trations of 300, 1,000, and 2,000 ug/g of feed. Given that the
daily ration is approximately 3 percent of the body weight, these
feed concentrations are equivalent to approximate dosages of 9, 30,
and 60 mg/kg body weight, respectively. The treated diets were fed
for 28 days, and resulting concentrations of 2,4-D and 2,4-DCP in
several edible tissues were determined (Table 2). with a detection
limit of 0.05 ug/g, analysis did not detect 2,4-DCP in the fat or
muscle of cattle and sheep, even at the highest dose levels. How-
ever, the kidney and liver were found to contain large amounts of
C-10
-------
TABLE 2
2,4-D and 2,4-DCP Residues (in mg/kg)
in Sheep and Cattle Fed 2,4-Da
2,4-D (Dose mg/kg body weight/day)
Sheep
Compound
2,4-D
2,4-DCP
2,4-D
2,4-DCP
2,4-D
2,4-DCP
2,4-D
2,4-DCP
60
0.06
< 0.05
0.10
£ 0.05
0.98
0.16
9.17
0.26
60b
Muscle
40.05 4
40.05 4
Fat
9
0.05
0.05
0.15 0.13
<0.05 4*0.05
Liver
0.29 <
0.15
Kidney
0.37
0.07
0.05
0.11
2.53
0.56
Cattle
30 60
*0.05 0.07
-------
2,4-DCP proportional to the dose given. Furthermore, when sheep
were withdrawn from 2,4-D for one week, measurable amounts of 2,4-
DCP were still detected. Based on the limited evidence presented,
the liver appeared to retain 2,4-DCP for longer periods than did
the kidney. The data presented do not allow accurate calculation
of a depletion rate, nor can the total time period of measurable
residues be ascertained.
6)
Sherman, et al. (1972) fed technical grade Nemacide^ [0-{2,4-
dichlorophenyl)-0,0-diethyl phosphorothioate] at 50, 100, 200, and
800 ug/g of feed to laying hens for 55 weeks. Analysis for 2,4-DCP
(a metabolite of Nemacide^ by gas-liquid chromatography (detection
limit 0.006 to 0.208 ug/g) resulted in detection of 2,4-DCP resi-
dues in liver and yolk, but not in muscle or fat. Details of the
analytical findings are presented in Table 3. As in the studies of
Clark, et al. (1975), there does appear to be some predilection of
2,4-DCP for liver, even when formed by biotransformation from two
parent compounds. In the hens studied, liver 2,4-DCP concentration
decreased as the dosage of Nemacide^ was decreased. The highest
mean liver level of 2,4-DCP found in hens was 0.56 ug/g, identical
to a mean level of 0.56 ug/g found in the kidneys of cattle fed 300
ug 2,4-D/g of feed (the dosage level that most closely approximates
possible field exposure) by Clark and coworkers (1975). It should
be noted that the Sherman study was strictly a laboratory study,
using conditions that are not likely to occur in the field. How-
ever, in a worst-case exposure situation, the consumption of 2,4-
DCP-contaminated chicken liver and cattle kidney could result in
approximately equivalent human exposure.
C-12
-------
TABLE 3
2,4-Dichlorophenol Residues in Laying Hens fed Nemacide^
[O-(2,4-dichlorophenol)-0,O-diethyl phosphorothioate]a
Nemacide^ Feed
Concentration
in ppm
Days since
Withdrawal *
from Nemacide
Residues of 2,4-DCP (ppm)
mean (and range)
Liver
Egg Yolk
800
200
100
50
0
5
7
10
14
21
0
7
14
21
0
7
14
21
0
7
14
21
0.47(0.14-0.68)
0.50(0.25-0.75)
0.27(0.06-0.48)
0.19(0.11-0.27)
0.38(0.31-0.44)
0.30(0.24-0.35)
0.14(0.10-0.18)
0.36(0.07-0.64)
0.26(0.25-0.26)
0.56
0.15( <0.05-0.33)
0.05
0.31(0.16-0.46)
0.18(0.14-0.22)
0.06( <0.05-0.11)
0.05
0.61(0.34-0.75)
0.27
<0.12
0.15(0.12-0.17)
0.15 «,0.12-0,21)
Modified from Sherman, et al. 1972
C-13
-------
Bjerke, et al. (1972) dosed dairy cows for three weeks with
2,4-D concentrations as high as 1,000 mg/kg of diet. 2,4-DCP was
not found in the milk or cream of treated cows.
The results of Clark, et al. (1975) can be used to calculate a
worst case estimate for the degree of human exposure to 2,4-DCP
from consumption of contaminated meat. Assuming (1) an average
forage yield of two tons (1,818 kg) per acre, (2) the retention of
all herbicide on the treated plants, (3) an application rate of 1
Ib (454 gins) of 2,4-D per acre, and (4) consumption by an animal of
3 percent of its body weight per day in forage, then the dosage
delivered to an animal eating forage contaminated with this level
of 2,4-D would be approximately 7 mg 2,4-DCP/kg body weight. This
amount corresponds roughly to the lowest dosage (9 mg/kg body
weight) that was administered to cattle and sheep by Clark and his
colleagues. Based on the results of Clark, et al., it is reason-
able to expect that cattle fed a constant diet of forage contami-
nated with 2,4-D applied at commercial rates would accumulate 2,4-
DCP concentrations of approximately 0.11 yg/g of liver and 0.56
yg/g of kidney.
If a 70 kg person consumed 0.5 kg of kidney daily at a 2,4-DCP
residue concentration of 560 yg/kg, that person would be consuming
approximately 280 ug of 2,4-OCP, or 4.0 ug/kq body weight, daily.
If that person also ingested 36 ug 2,4-DCP/kg body weight/day in
contaminated drinking water, as calculated from 2,4-DCP levels in
water downstream from a 2,4-DCP manufacturing plant (see Ingestion
from Water section), the resultant daily 2,4-dichlorophenol dosages
would total 40 yg/kg. It is therefore clear that the water would
C-14
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contribute 90 percent of this highest calculated daily dosage of
2,4-DCP.
It should be emphasized that an exposure level of 4 ug 2,4-
DCP/kg body weight/day is a worst case example for food intake. It
would only occur if a person (1) ate 0.5 kg of kidney per day and
(2) all the kidney consumed was contaminated with 0.11 ug 2,4-
DCP/g. This contamination level would probably occur only if the
cattle were fed a constant diet of 2,4-D-sprayed forage, since
experimental evidence (Clark, et al. 1975; Zielinski and Fishbein,
1967) indicates that levels of 2,4-DCP in animal tissue diminish
rapidly following withdrawal of 2,4-D from the diet.
A bioconcentration factor (BCF) relates the concentration of a
chemical in aquatic animals to the concentration in the water in
which they live. The steady-state BCFs for a lipid-soluble com-
pound in the tissues of various aquatic animals seem to be propor-
tional to the percent lipid in the tissue. Thus, the per capita
ingestion of a lipid-soluble chemical can be estimated from the per
capita consumptions of fish and shellfish, the weighted average
percent lipids of consumed fish and shellfish, and a steady-state
BCF for the chemical.
Data from a recent survey on fish and shellfish consumption in
the United States were analyzed by SRI International (U.S. EPA,
1980). These data were used to estimate that the oer caoita con-
sumption of freshwater and estuarine fish and shellfish in the
United States is 6.5 g/day (Stephan, 1980). In addition, these
data were used with data on the fat content of the edible portion
of the same species to estimate that the weighted average percent
C-15
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lipids for consumed freshwater and estuarine fish and shellfish
is 3.0.
No measured steady-state bioconcentration factor is available
for 2,4-dichlorophenol, but the equation "Log BCF = (0.85 Log P) -
0.70" (Veith, et al. 1979) can be used to estimate from the octa-
nol-water partition coefficient (P) the BCF for aquatic organisms
that contain about 7.6 percent lipids (Veith, 1980). Based on an
average log P value of 3.19 (Hansch and Leo, 1979), the steady-
state bioconcentration factor for 2 ,4-dichloroohenol is estimated
to be 103. An adjustment factor of 3.0/7.6 = 0.395 can be used to
adjust the estimated BCF from the 7.6 percent lipids on which the
equation is based to the 3.0 percent lipids that is the weighted
average for consumed fish and shellfish. Thus, the weighted aver-
age bioconcentration factor for 2,4-dichloroohenol and the edible
portion of all freshwater and estuarine aquatic organisms consumed
by Americans is calculated to be 103 x 0.395 = 40.7.
Inhalation
There is no direct evidence to indicate that humans are ex-
posed to significant amounts of 2,4-DCP through inhalation. Al-
though the compound is volatile, no quantitative studies of inhala-
tion exposure or general environmental contamination have been
found.
Dermal
Dermal exposure to 2,4-DCP would most likely occur during the
manufacture, transport, or handling of the compound. Due to its
lipophilic nature and low degree of ionization at physiologic oH,
absorption of 2,4-DCP would be expected; however, no data relating
to dermal absorption have been found.
C-16
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PHARMACOKINETICS
Absorption
No information concerning the direct absorption of 2,4-dichlo-
rophenol in humans or animals was found. Toxicity data to be
developed later confirm the existence of systemic toxicosis, indi-
cating that 2,4-DCP is absorbed by several routes.
Because of their high lipid solubility and low ionization at
physiological pH, dichlorophenols would be expected to be readily
absorbed following ingestion.
Distribution
No information was found concerning distribution of 2,4-DCP in
man. The previously discussed (see Ingestion from Food section)
animal studies (Clark, et al. 1975; Sherman, et al. 1972) demon-
strated distribution of 2,4-DCP in liver, kidney, and egg (see
Tables 2 and 3).
Metabolism
The biotransformation of 2,4-DCP in humans has not been re-
ported. No information could be found concerning the metabolism of
2,4-DCP administered directly to experimental animals. However, a
limited amount of information on the metabolism of 2,4-DCP derived
from administration of gamma and beta benzene hexachloride (BHC) to
14
mice was reported by Kurihara (1975). Mice were given C -labeled
gamma- or beta-BHC by intraperitoneal injection, and the appearance
of metabolites in the urine was monitored. 2,4-DCP and 2,4-DCP
conjugates were found and identified primarily as glucuronides and
sulfates (Table 4). Administration of gamma-BHC resulted in a
majority of the 2,4-DCP being conjugated as the alucuroni^e, while
beta-BHC administration resulted in a greater amount of sulfate
C-17
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TABLE 4
Urinary 2,4-DCP Metabolites of Benzene
Hexachloride in Mice3
BHC I some r
gamma-BHC
beta-BHC
Form of
Glucuronide
4-5%b
1-2%
2,4-DCP
Sulfate
0-1%
3%
Total
4-6%
4-5%
Source: Kurihara, 1975
Percent of total metabolites
C-1B
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conjugate. Assuming that the mouse biotransforms 2,4-DCP resulting
from endogenous metabolism in a manner similar to 2,4-DCP directly
administered, then sulfate and glucuronide conjugation appear to be
major metabolic pathways.
Excretion
2,4-D has been found to be rapidly excreted in the urine of
mice (Zielinski and Fishbein, 1967), rats (Khanna and Fang, 1966),
sheep (Clark, et al. 1964), and swine (Erne, 1966a,b) under various
dosing conditions. The phenoxy herbicide MCPA was also rapidly
excreted in cattle urine (Bache, et al. 1964b). However, excretion
data from studies using 2,4-DCP are not extensive, and no infor-
mation was found for 2,4-DCP excretion in man.
Karapally, et al. (1973) found that when rabbits were given
radioactive gamma-BHC, 2.5 percent of total radioactivity in the
urine was due to 2,4-DCP. Data presented did not allow for deter-
mination of body burden or half-life. Shafik, et al. (1973) admin-
istered a daily dose of Nemacide-^ in peanut oil orally to rats for
three days. After administration of 1.6 mg Nemacide^, 67 percent
of that compound appeared in urine as 2,4-DCP within three days.
With a dosage of 0.16 mg Nemacide , 70 oercent of the pesticide
appeared as 2,4-DCP within 24 hours. Work cited earlier (Kurihara,
1975) indicated the appearance of metabolites of 2,4-DCP in urine
as a result of gamma- and beta-BHC administration (see Table 4).
EFFECTS
Acute, Subacute, and Chronic Toxicity
Farquharson, et al. (1958) indicated that the toxicity of
chlorophenols tends to increase as chlorination is increased.
C-19
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The mechanism of toxic action for 2,4-DCP in mammalian systems
_iri vivo has not been well defined. Limited ^ri vitro studies indi-
cate two potential actions. 2,4-DCP inhibits oxidative phosphoryl-
ation in rat liver mitochondria and rat brain homogenates (Farqu-
harson, et al. 1958; Mitsuda, et al. 1963). According to Mitsuda,
et al. (1963) , inhibitory activity of chlorophenols was roughly
correlated with the dissociation constant of the inhibitor. In
addition, chlorine atoms on the ortho position weakened the activ-
ity of mono- and dichlorophenols as oxidative inhibitors. A con-
centration of 4.2 x 10" M 2,4-DCP inhibited oxidative phosphoryla-
tion by 50 percent in rat liver mitochondria. By comparison, pen-
tachlorophenol was approximately 40 times more active, and dinitro-
phenol was twice as active in inhibiting oxidative phosphorylation.
Stockdale and Selwyn (1971) reported observations suggesting
that the phenol-induced mediation of the passage of protons across
the inner mitochondrial membrane is sufficient to cause uncoupling
of oxidative phosphorylation. They further noted that phenols have
direct effects on the enzyme ATPase as well as on one or more compo-
nents of the electron transport system; however, neither of these
effects is actually involved in the uncoupling process.
Farquharson, et al. (1958) offered the conclusion that chloro-
phenols with pK values of 7.85 or less appear to be acutely associ-
ated with production of marked hypotonia and early onset of rigor
mortis after death. Similar clinical effects are associated with
well known oxidative uncouplers, such as 2,4-dinitrophenol and pen-
tachlorophenol. Relatively few studies of the acute or subacute
toxicity of 2,4-DCP have been reported. The acute LD5Q values
determined by several investigators are presented in Table 5.
C-20
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TABLE 5
Acute Mammalian Toxicity of 2,4-DCP
Species
Route of
Administration
LD50
(mg/kg)
Reference
Rat
Rat
Rat
Rat
Mouse
Oral
Subcutaneous
Intraperitoneal
Oral
Oral
580
1,730
430
4,000
1,600
Deichmann, 1943
Deichmann, 1943
Farquharson, et al. 1958
Kobayashi, et al. 1972
Kobayashi, et al. 1972
C-21
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In the study by Farquharson, et al. (1958) , acute poisoning of
rats following intraperitoneal 2,4-DCP injection appeared to be
characterized by the onset of hypotonia two to three minutes after
dosing. This effect began in the hindlimbs and moved forward until
the rats were prostrate. Eye reflexes were weakened and there was
no withdrawal from toe pinch. Muscle twitches rarely occurred
spontaneously and could not be evoked by auditory or tactile stimu-
li. Rectal temperature was only slightly decreased. Initial dose-
induced polypnea was followed by slowed respiration and dyspnea
as coma ensued. Rigor mortis appeared earlier in rats killed with
2,4-DCP than in control rats killed with ether.
The oral LDc0 derived by Deichmann (1943) appears at odds with
the findings of Kobayashi, et al. (1972). Deichmann used fuel oil
as a solvent, which may have enhanced rapid uptake of 2,4-DCP. The
vehicle for the Kobayashi studies could not be determined. None-
theless, from the LD5Q values, it appears that 2,4-DCP would con-
stitute an acute hazard only following massive exposure.
In a subacute (10-day) study, Kobayashi, et al. (1972) found
that all mice survived when 2,4-DCP at 667 mg/kg body weight was
given orally. They derived LDcg figures for this study which ap-
pear similar to those listed for the acute studies (see Table 5).
In the same study (Kobayashi, et al. 1972), male mice were also fed
2,4-DCP in the diet over a 6-month period. Parameters evaluated
included average body weight, food consumption, orqan weight, glu-
tamic oxaloacetate transaminase, glutamic pyruvic transaminase,
erythrocyte counts, leucocyte counts, and histopathological
changes. The estimated dose levels were 45 mg/kg/day, 100 mq/kg/
C-22
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day, and 230 mg/kg/day, corresponding to dietary 2,4-DCP concentra-
tions of 50C, 1,000, and 2,000 ug/g, respectively. No adverse
effects were noted in mice at any dose level, except for some
microscopic non-specific liver changes after the maximum dose.
These changes included infiltration of round cells and swelling of
hepatocytes, with some differences in cell size. Two animals were
reported to have "dark cells" in the liver. (To the author's
knowledge, this term is not commonly used in the United States, and
its meaning is not clear.) Kobayashi, et al. concluded that 100
mg/kg/day is a maximum no-effect level in mice.
No other chronic toxicity studies using 2,4-dichloroohenol
have been found. One report in the literature (Bleiberg, et al.
1964) has suggested a possible role of 2,4-DCP in acquired chlor-
acne and porphyria in workers manufacturing 2,4-DCP and 2,4,5-tri-
chlorophenol (2,4,5-TCP). The workers involved were also exposed
to acetic acid, phenol, monochloroacetic acid, and sodium hydrox-
ide. Since various dioxins (including 2,3,7,8-tetrachloro-diben-
zo-p-dioxin (TCDD), which has been associated with chloracne) have
been implicated as contaminants of 2,4,5-TCP, the role of 2,4-DCP
in inducing chloracne and porphyria is not conclusive (Huff and
Wassom, 1974).
Synergism and/or Antagonism
Reports of studies directly assessing the synergism or antago-
nism of 2,4-dichlorophenol by other compounds were not found.
Since 2,4-DCP is an uncoupler of oxidative phosphorylation (Mit-
suda, et al. 1963), it may be expected that concomitant exposure
to other uncouplers (e.g., pentachlorophenol, dinitrophenol) would
C-23
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enhance that effect. In addition, exposure to gamma- or beta-BHC,
2,4-D, and nitrofen could add slightly to any primary body burden
of 2,4-DCP.
Any agent causing liver damage sufficient to decrease the con-
jugation of 2,4-DCP with glucuronide or sulfate could conceivably
alter the excretion and/or toxicity of the oarent compound. How-
ever, there are no specific studies to reflect such an effect.
Teratogenicity
Pertinent data could not be located in the available litera-
ture concerning the teratogenicity of 2,4-DCP.
Mutagenicity
No studies were found which addressed the mutagenicitv of 2,4-
dichlorophenol in mammalian systems. Amer and Ali (1968, 1969) did
report some effects of 2,4-DCP on mitosis and meiosis in flower
buds and root cells of vetch (Vicia faba). Changes included meiot-
ic alterations of chromosome stickiness, lagging chromosomes, and
anaohase bridges when flower buds were sprayed with 0.1 M 2,4-DCP.
Mitotic changes of chromosome stickiness, lagging chromosomes, dis-
integration, bridging, disturbed proohase and metaphase, and occa-
sional cytomyxis were seen in root cells exoosed to 62.5 mg/1 DCP.
Later studies (Amer and Ali, 1974) further confirmed the effect of
chromosome stickiness, lagging chromosomes, and fragmentation in
35-day-old Vicia faba. The relationship of these changes to alter-
ations in mammalian cells has not been established.
Carcinogenicity
Repeated application of ohenol and some substituted ohenols
has demonstrated promoting, as well as complete, tumorigenic activ-
C-24
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ity (Boutwell and Bosch, 1959). In the Boutwell and Bosch study,
two trials included evaluation of 2,4-DCP as a promoter. In one
trial, 25 pi of a 20 percent solution of 2,4-DCP in benzene was
applied twice weekly for 15 weeks to female Sutter mice two to
three months of age. The other trial was identical, except that
2,4-DCP was applied for 24 weeks. Application in both trials fol-
lowed an initiating dose of 0.3 percent dimethyl-benzanthracene
(DMBA) in benzene.
The 2,4-DCP dose used corresponds to 5 mg of compound per
mouse at each application, or 10 mg/week when applied twice weekly.
Sutter mice two to three months old would be expected to weigh 35
grams, so that the dose rate would be 40.82 mg/kg body weight.
Tumorigenic response was measured as follows:
1) The percentage of surviving mice bearing one or more
papilloma was ascertained.
2) The number of papillomas on all surviving mice was
totaled and divided by the number of survivors to
give the average number of papillomas per surviving
mouse.
3) The number of mice bearing malignant tumors was
determined.
Results of the promoter trial with 2,4-DCP are presented in
Table 6. Related promoter experiments with phenol and the two ben-
zene controls are included for comparative purposes. Boutwell and
Bosch concluded that the promoting activity of 2,4-DCP is similar
to that of phenol. However, no statistical analyses nor dose-
response data were included to support this comparison.
To see if there was a statistically significant difference
between the 2,4-DCP-treated mice and the benzene controls, a Fisher
C-25
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TABLE 6
Appearance of Skin Tumors in Mice Treated Cutaneoualy with Phenols following
a Cutaneous Dose of 0.3% Dimethyl-benzanthracene (DMBA) in Acetone9
Treatments
Benzene control
Benzene control
10% phenol in
benzene in DMBA
20% phenol in
acetone
20% phenol in
benzene
20% 2,4-DCP
in benzene
20% 2,4-DCP
in benzene
Time Animals
Examined
(week)
15
24
20
12
24
15
24
No. of Mice
(survivors/total)
15/20
27/32
24/30
21/24
10/33
27/33
16/23
Survivors
with PapilloMS
7
11
33
58
100
48
75
Average
Papilloaas
per Survivor
0.07
0.15
0.62
-
3.20
1.07
1.62
Survivors with
Epithelial Carcinomas
0
0
13
5
20
11
6
Source: Modified from Boutwe11 and Bosch, 1959
All received DMBA except where stated
C-26
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exact test was undertaken for this document. Tumor incidence was
derived with the assumption that only survivors were examined for
tumors. The calculated results are presented in Table 7.
This analysis indicates that (1) the higher incidence of
papillomas in both 2,4-DCP-treated groups was not attributable to
chance, and (2) the carcinoma incidence was not significantly ele-
vated over controls.
This statistical exercise should not obscure a number of con-
siderations that could affect the meaningfulness of the results.
(1) The study used dermal application of a phenolic compound at 20
percent concentration in organic solvents. This concentration is
high enough to destroy hair follicles and sebaceous glands. The
papillomatous response observed may have developed in response to
chemical and/or physical damage from application of an irritant
compound. (2) Even with the harsh treatment, no malignant neo-
plasia was observed, except when DMBA was used as an initiator.
The only neoplasia observed was at the site of direct application.
(3) Pathological identification of benign and malignant tumors was
done on a gross level, with only periodic confirmation by micro-
scopic examination. (4) The mice were housed in creosote-treated
wooden cages, which themselves were capable of initiating a carci-
nogenic response.
The report of Boutwell and Bosch (1959) is the only one found
that deals with the tumorigenicity of 2,4-DCP. However, since the
study was designed primarily to detect promoting activity, the
effect of 2,4-DCP as a primary carcinogen is not well defined.
C-27
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TABLE 7
Results of Fisher Exact Test Applied to Data
from Boutwell and Bosch (1959)
Treatment „, ^ration of
Treatment (wks)
Benzene control (I) 15
20% 2,4-DCP 15
in benzene
Benzene control (II) 24
20% 2,4-DCP in 24
benzene
Incidence of P-value I£cid.e"S:e ?f P-value
Danii i^mae, vs- Epithelial vs.
fapiiiomas control Carcinoma Control
1/15
13/27 0.61 x 10~2
3/27
12/16 0.36 x 10"4
0/15
3/27
0/27
1/16
-
0.2548
-
0.3721
C-28
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The route of administration is not approoriate to the model
for carcinogenic risk assessment and has no established relation-
ship to oral exposure. Overall, the study does present evidence
that 2,4-DCP may be a possible promotor, and the work may be appli-
cable to evaluating the hazard of skin or respiratory exposure to
2,4-DCP, alone or concurrent with other chemicals.
Other Effects
An odor threshold for 2,4-DCP in water has been reported by at
least three investigators. Hoak (1957) determined the odor thresh-
old of 2,4-DCP to be 0.65 yg/1 at 30°C and 6.5 yg/1 at 60°C. Deter-
mination of the detectable odor was made by a panel of two or four
people comparing flasks of test water to a flask of odor-free
water. The lowest concentration detected by any panel member was
taken as the odor threshold. Hoak speculated that odor should
become more noticeable as temperature increases; however, in evalu-
ating a series of chlorophenols and cresols, it was found that some
compounds had higher odor thresholds at 30°C, and others were high-
er at 60°C.
Burttschell, et al. (1959) made dilutions of chlorophenol in
carbon-filtered tap water and used a panel of four to six people to
evaluate odor. Tests were carried out at room temperature, which
the investigator estimated to be 25°C. If a panel member's re-
sponse was doubtful, the sample was considered negative. The geo-
metric mean of the panel responses was used as the odor threshold.
For 2,4-DCP the threshold was 2 ug/1.
Dietz and Traud (1978) used a panel composed of 9 to 12
persons of both sexes and various age groups to test the organolep-
C-29
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tic detection thresholds for 126 phenolic compounds. TO test for
odor thresholds, 200 ml samples of the different test concentra-
tions were placed in stoppered odor-free glass bottles, shaken for
approximately five minutes, and sniffed at room temperature (20-
22°C). For each test, water without the phenolic additive was used
as a background sample. The odor tests took place in several indi-
vidual rooms in which phenols and other substances with intense
odors had not been used previously. Geometric mean values were
used to determine threshold levels. To determine taste threshold
concentrations of selected phenolic compounds, a panel of four test
individuals tested water samples containing various amounts of ohe-
nolic additives. As a point of comparison, water without phenolic
additives was tasted first. Samples with increasing phenolic con-
centrations were then tested. Between samples, the mouth was
rinsed with the comparison water and the test person ate several
bites of dry white bread to "neutralize" the taste. Geometric mean
detection level values for both tests provided threshold levels of
0.3 ug/1 for taste and 40 yg/1 for odor for 2,4-DCP.
None of these three studies, however, indicated whether the
determined threshold levels made the water undesirable or unfit for
consumption.
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CRITERION FORMULATION
Existing Guidelines and Standards
Presently, no standard for exposure to 2,4-OCP in drinking or
ambient water has been set, although a standard of 0.1 mg/1 for
2,4-D, a related compound, has been set fNational Academy of Sci-
ences (WAS), 1977].
Current Levels o€ Exposure
Human exposure to 2,4-DCP has not been monitored, but a worst
case estimate of 40 yg 2,4-DCP/kg body weight/day of exposure was
presented in the Ingestion from Food section.
Special Groups at Risk
The only group expected to be at risk from high exposure to
2,4-DCP is industrial workers involved in the manufacturing or
handling of 2,4-DCP and 2,4-0. No data were found to relate expo-
sure or body burden to conditions of contact with 2,4-DCP.
Basis and Derivation of Criterion
Insufficient data exist to indicate that 2,4-DOP is a carcino-
genic agent. The only study performed (Boutwell and Bosch, 1959)
was designed to detect promoting activity, and the effect of 2,4-
DCP as a primary carcinogen could not be evaluated. Also, the
route of administration (dermal) in this study is inappropriate for
use in the linear model for carcinogenic risk assessment (see Car-
cinogenicity section).
Minimal health effects data exist on the acute and chronic
effects of 2,4-DCP. Only one study of a chronic nature (Kobayashi,
et al. 1972) was found. Kobayashi and colleagues determined a
chronic (6-month) no-effect level for 2,4-DCP to be 1,000 ug/q of
diet for mice, which was equivalent to 100 mg/kq body weight/dav.
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An equivalent daily dose for a 70 kg adult human would be 7,000
mg/day (100 mg/kg/day x 70 kg). Applying an uncertainty factor of
1,000 as suggested by the National Academy of Sciences ^afe Drink-
ing Water Committee (1977), the Acceptable Daily Intake (ADI) for a
70 kg adult human would be 7,000 mg T 1/000 = 7 mg. Solving the
equation (2L)(C) + (C) (BCF) (fish consumption/day) = ADI, the water
quality criterion (C) can be computed:
(2L) (C) + (C) (40.7) (0.0065) = 7 mg
(2L)(C) •+• (C)(0.26455) = 7 mg
C = 7 "ig
2.26455L
C = 3.09 rag/1
where:
7 mg = the calculated daily exposure for a 70 kq person
(ADI) based on the above conditions
2L = amount of drinking water consumed/day
0.0065 kg = amount of fish consumed/day
C = maximum permissible level in water based on above
conditions
Thus, a criterion level based entirely upon toxicological data
would be 3.09 mg/1.
Human health is a subjective measurement in many respects.
The organoleptic properties of 2,4-DCP could conceivably alter
human health by causing a decrease in water consumption. This
might be of particular importance to individuals with certain renal
diseases or in instances where dehydration occurs as a result of
vigorous exercise, manual labor, or hot weather.
C-32
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Since the odor and taste detection threshold concentrations
for 2,4-dichlorophenol are well below any toxicity-based criterion
level that may be derived, the ambient water quality criterion is
based on organoleptic data. It should be emphasized that this cri-
terion is based on aesthetic qualities rather than health effects.
However, to the effect that this criterion is below the level de-
rived from the chronic toxicity study of Kobayashi, et al. (1972),
it is likely to also be protective of human health.
The data of Hoak (1957), Burttschell, et al. (1959), and Dietz
and Traud (1978) all indicated that low microgram concentrations of
2,4-dichlorophenol in water are capable of producing a discernable
odor. Dietz and Traud further observed a distinct flavor altera-
tion of water at sub-microgram levels of 2,4-DCP. ^he Burttschell,
et al. (1959) and Dietz and Traud (1978) studies did not indicate a
range of responses; however, because of the variability of respons-
es inherent in such procedures, it is certainly possible that the
odor threshold for some evaluators (at least in the Burttschell
group) would extend downward toward the 0.65 ug/1 figure of Hoak.
Thus, the data from these three studies are considered to be rea-
sonably mutually supportive (i.e., Hoak's 0.65 ug/1 for odor,
Burttschell's 2.0 ug/1 geometric mean value for odor, and Dietz and
Traud's geometric mean values of 40 ug/1 for odor and 0.3 ug/1 for
taste) .
Therefore, based on the prevention of undesirable organoleptic
qualities, the criterion level for 2,4-dichlorophenol in water is
0.3 ug/1. This level should be low enough to prevent detection of
objectionable organoleptic characteristics and far below minimal
C-33
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no-effect concentrations determined in laboratory animals. As more
substantive and reliable data become available in the future, a
criterion level based on human health effects mav be more confi-
dently postulated.
It should be emphasized that data are needed in the following
areas to properly evaluate any hazard from 2,4-DCP:
1) Monitoring of worker exposure to 2,4-DCP in indus-
tries manufacturing or using the chemical.
2) Monitoring of public water supplies and industrial
and municipal effluents to determine an expected
range of concentrations under differing environ-
mental conditions.
3) More definitive studies of residue kinetics of 2,4-
DCP in food animals which are exposed to products
capable of generating 2,4-DCP.
4) Evaluation of chronic toxicity, mutagenicity, and
teratogenicity of 2,4-DCP using currently accept-
able techniques.
5) A carcinogenicity study of 2,4-DCP using the oral
route and evaluated according to current protocols.
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Aly, O.M. and S.D. Faust. 1964. Studies on the fate of 2,4-n and
ester derivatives in natural surface waters. Jour. Agric. Food
Chem. 12: 541.
Amer, S.M. and E.M. All. 1968. Cytological effects of pesticides.
II. Meiotic effects of some phenols. Cytologia. 33: 21.
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