vvEPA
United States
Environmental Protection^
Agency '•*<•''
Office of Water
Regulations and Standards
Criteria and Standards Division
Washington DC 20460
EPA 440/5-80-066
October 1980
C.I
Ambient
Water Quality
Criteria for
Phenol
-------
AMBIENT WATER QUALITY CRITERIA FOR
PHENOL
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
Em*'r;:~:,--:.'';ri*7.l Fro^Tion Agency
v.'.;/',.;..,-:^ CCJ04
i
-------
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.
i
-------
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
-------
ACKNOWLEDGEMENTS
Aquatic life Toxicology:
William A. Brungs, ERL-Narragansett
U.S. Environmental Protection Agency
David J. Hansen, ERL-Gulf Breeze
U.S. Environmental Protection Agency
Mammalian Toxicology and Human Health Effects:
Rolf Hartung (author)
University of Michigan
John F. Risher (doc. mgr.) ECAO-Cin
U.S. Environmental Protection Agency
Donna Sivulka (doc. mgr.) ECAO-Cin
U.S. Environmental Protection Agency
Patrick Durkin
Syracuse Research Corporation
Vincent N. Finelli
University of Cincinnati
Van Kozak
University of Wisconsin
Steven D. Lutkenhoff, ECAO-Cin
U.S. Environmental Protection Agency
Alan B. Rubin
U.S. Environmental Protection Agency
Joseph Arcos
Tulane Medical Center
Richard Carchman
Medical College of Virginia
William B. Deichman
University of Miami
David B. Faukhauser
University of Cincinnati
Frederick Hamblet, HERL
U.S. Environmental Protection Agency
Geraldine L. Krueger
University of Cincinnati
Gary Osweiler
University of Missouri
Peter Toft
Health and Welfare, Canada
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.
-------
TABLE OF CONTENTS
Page
Criteria Summary
Introduction A-l
Aquatic Life Toxicology B-l
Introduction B-l
Effects B-l
Acute Toxicology B-l
Chronic Toxicology B-3
Plant Effects B-3
Residues B-3
Miscellaneous B-3
Summary B-4
Criteria B-5
References B-22
Mammalian Toxicology and Human Health Effects C-l
Introduction C-l
Exposure c-2
Ingestion from Water C-2
Ingestion from Food C-8
Inhalation C-12
Dermal C-15
Pharmacokinetics C-15
Absorption C-15
Distribution C-16
Metabolism C-17
Excretion C-18
Effects C-18
Acute, Subacute, and Chronic Toxicity C-18
Synergism and/or Antagonism C-22
Teratogenicity and Mutagenicity C-22
Carcinogenic!ty C-22
Criterion Formulation C-29
Existing Guidelines and Standards C-29
Current Levels of Exposure C-29
Special Groups at Risk C-30
Basis and Derivation of Criterion C-32
References C-33
-------
CRITERIA DOCUMENT
PHENOL
CRITERIA
Aquatic Life
The available data for phenol indicate that acute and chronic
toxicity to freshwater aquatic life occur at concentrations as low
a-ja? 10,200 and 2,560 ug/1, respectively, and would occur at lower
concentrations among species that are more sensitive than those
tested.
The available data for phenol indicate that toxicity to salt-
water aquatic life occurs at concentrations as low as 5,800 ug/1
and would occur at lower concentrations among species that are more
sensitive than those tested. No data are available concerning the
chronic toxicity of phenol to sensitive saltwater aquatic life.
Human Health
For comparison purposes, two approaches were used to derive
criterion levels for phenol. Based on available toxicity data, for
the protection of public health, the derived level is 3.5 mg/1.
Using available organoleptic data, for controlling undesirable
taste and odor qualities of ambient water, the estimated level is
0.3 mg/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
-------
INTRODUCTION
Phenol is a large volume industrial chemical produced almost
entirely as an intermediate for the preparation of other chemicals.
These include synthetic polymers such as phenolic resins, bis-
phenol and caprolactam plastics intermediates, and chlorinated and
alkylated phenols.
Phenol, occasionally referred to as "carbolic acid", is a
monohydroxybenzene which is a clear, colorless (light pink when im-
purities are present), hygroscopic, deliquescent, crystalline sol-
id at 25°C„(Manufacturing Chemist Assoc., 1964; Kirk and Othmer,
1963; Weast, 1974). It has the empirical formula CgHgO, a molecu-
lar weight of 94.11, a specific gravity of 1.071 at 25°C, and a
vapor pressure of 0.3513 mm Hg at 25°C .(Patty, 1963; Manufacturing
Chemists Assoc., 1964; Am. Ind. Hyg. Assoc., 1957; Sax, 1975).
Phenol has a melting point of 43°C and a boiling point of 182°C at
760 mm Hg (Weast, 1974).
Phenol has a water solubility of 6.7 g/100 ml at 16°C and is
soluble at all proportions in water at 66°C. It is also soluble in
relatively non-polar solvents such as benzene, petrolatum, and oils
(Patty, 1963; Kirk and Othmer, 1963; Weast, 1974).
Due to the electronegative character of the phenyl group,
phenol exhibits weakly acidic properties. It possesses a pKa of
9.9 to 10.0 and readily reacts with strong bases such as NaOH, KOH,
etc., to form salts called phenoxides (Weast, 1974; Kirk and Oth-
mer, 1963). Phenoxides exist in highly alkaline aqueous solutions
and many, particularly the sodium and potassium salts, are readily
soluble in water.
A-l
-------
Natural phenol is produced by the distillation of coal tar,
although this source constitutes only 1 to 2 percent of total
phenol production ,,(Kirk and Othmer, 1963). The cumene process
represents the most popular route of phenol production and involves
two basic steps. Cumene is oxidized to cumene hydroperoxide with
air in the presence of an alkali catalyst and is subsequently
cleaved to phenol and acetone with the aid of a sulfuric acid cata-
lyst, (Cook, 1977). Other methods of commercial production include
the toluene oxidation process and the benzene sulfonation process
(Faith, et al. 1975). In the former process, toluene is oxidized
to benzoic acid and reduced to phenol, using a copper catalyst.
The latter method involves the sulfonation of benzene to benzene-
sulfonic acid, its neutralization with sodium sulfite or carbonate
to form sodium benzenesulfonate and the subsequent reaction of this
compound with fused caustic soda at high temperatures. The sodium
phenate or sodium salt is then acidified with sulfur dioxide to
form the phenol (Faith, et al. 1975) . This purity of most syn-
thetic phenols is greater than 99.5 percent, while the purity of
natural sources ranges from 80 to 82 percent and 90 to 92 percent,
depending upon the source and method of production. The commercial
products generally contain an impurity which changes the melting
point (Spector, 1956; Stecher, 1968).
Phenol or phenolic wastes also are produced during the coking
of coal, distillation of wood, operation of gas works and oil
refineries, manufacture of livestock dips, as a normal constitutent
of human and animal wastes, and microbiological decomposition of
organic matter jBulick, 1950; Mischonsniky, 1934).
A-2
-------
Phenol undergoes oxidation to a variety of products, such as
the benzenediols, benzenetriols, and derivatives of diphenyl and
diphenylene oxide, depending on the oxidizing agent and conditions
(Kirk and Othmer, 1963). However, phenol may be biochemically hy-
droxylated to ortho- and paradihydroxybenzenes and readily oxidized
to the corresponding benzoquinones. These may in turn react with
numerous components of industrial waters or sewage such as mercap-
tans, amines, or the -SH or -NH groups of proteins. In the absence
of these compounds, the quinones, especially the ortho- isomers,
can be quickly destroyed by hydrolytic oxidizing reactions (Stom,
1975) .
The hydroxyl group of phenol imparts a high degree of reactiv-
ity to the phenyl ring, particularly the ortho- and para- posi-
tions. Phenol has been shown to be highly reactive to chlorine in
dilute aqueous solutions over a wide pH range (Carlson and Caple,
1975; Middaugh and Davis, 1976). The chlorination of phenol in
aqueous solutions to form 2-chloro-, 4-chloro-, or higher chloro-
phenols has been demonstrated under conditions similar to those
used for disinfection of wastewater effluents (Aly, 1968; Barnhart
and Campbell, 1972) and represents a potential amplification of the
organoleptic problems associated with phenol contamination. Syn-
thesis of 2-chlorophenol within one hour in aqueous solutions con-
taining as little as 10 mg/1 phenol and 20 mg/1 chlorine has been
reported (Barnhart and Campbell, 1972). Other studies have re-
ported the formation of up to 1.7 ug/1 2-chlorophenol and other
chlorinated compounds during the chlorination or sewage effluents
and power plant cooling waters (Jolley, 1973; Jolley, et al. 1975).
A-3
-------
The photooxidation of phenol in water at alkaline pH has been
studied. Irradiation with a mercury arc lamp produced several
intermediate compounds and p-benzosemiquinone as the final product
(Tomkiewicz, et al. 1971; Cocivera, et al. 1972). Audureau, et al.
(1976) studied the photooxidation of phenol with ultraviolet
irradiation (253.7 nm) and concluded that the reaction initially
leads to the formation of a complex mixture of tri-and tetrahy-
droxybiphenyls, quinones and dihydroxybenzenes. Aqueous phenol
solutions irradiated with sunlight for seven days were reported to
degrade to hydroquinone and pyrocatechol (Perel1shtein and Kaplin,
1968). Subsequent irradiation of pyrocatechol with sunlight for
seven days yielded pyrogallol. The end products of photodecomposi-
tion were reported to be humic acids. Conversely, similar studies
utilizing natural sunlight as the source of irradiation indicated
that phenol concentrations in solutions of pure water remained
unchanged after ten days (Wilbaut-Isebree, 1964). However, phenol
degradation did occur in industrial sewage effluents and led to the
conclusion that unidentified microorganisms, not sunlight, were
responsible for the destruction of phenol.
The microbiological degradation of phenol has been widely
studied. Bayly, et al. (1966) reported the conversion of phenol to
catechol by Pseudomonas putida. Neujahr and Varga (1970) observed
the oxidation of phenol by both intact cells and extracts of the
microorganism, Trichosporon cutaneum. Buswell and Twomey (1975)
and Buswell (1975) demonstrated the ability of the thermophilic
bacteria, Bacillus stearothermophilus, to catabolize phenol. In
these studies, the bacteria first converted phenol to catechol and
A-4
-------
subsequently cleaved the aromatic ring to form 2-hydroxyir,uconic
semialdehyde. In view of the fact that phenol represented the pri-
mary carbon source provided to isolated and adapted microorganisms
in these studies, the importance or microbiological degradation
within the environment remains unclear.
Information concerning the presence and persistence, and fate
of phenol in the environment is incomplete or not available.
The widespread use of phenol as an important chemical inter-
mediate, the generation of phenolic wastes by industry and agricul-
ture, and the toxicological and organoleptic properties indicate
its importance in potential point source and nonpoint source water
contamination.
A-5
-------
REFERENCES
Aly, O.M. 1968. Separation of phenols in waters by thin-layer
chromatography. Water Res. 2: 287.
American Industrial Hygiene Association. 1957. Hygienic guide
series: Phenol. Am. Ind. Hyg. Assoc., Detroit.
Audureau, J., et al. 1976. Photolysis and photooxidation of phe-
nol in aqueous solutions. Jour. Chem. Phys. 73: 614.
Barnhart, E.L. and G.R. Campbell. 1972. The effect of chlorina-
tion on selected organic chemicals. U.S. Environ. Prot. Agency.
U.S. Government Print. Off., Washington, D.C.
Bayly, R.C., et al. 1966. The metabolism of cresols by a species
of Pseudomonas. Biochem. Jour. 101: 293.
Bulick, J. 1950. Phenolic Waste Waters. In; Pub. Health Eng.
Palivo. 30: 308 (Abst.)
Buswell, J.A. 1975. Metabolism of phenol and cresols by Bacillus
stearothermophilus. Jour. Bact. 17.
Buswell, J.A. and D.G. Twomey. 1975. Utilization of phenol and
cresols by Bacillus stearothermophilus Strain pH 24. Jour. Gen.
Microbiol. 87: 377.
A-6
-------
Carlson, R.M. and R. Caple. 1975. Organo-chemical Implication of
Water Chlorination. In; Proc. Conf. Environ. Impact Water Chlorin-
ation. p. 73.
Cocivera, M. , et al. 1972. Electron paramagnetic resonance and
nuclear spin polarization study of phenol in water. Jour. Am.
Chem. Soc. 94: 6598.
Cook, F.B. 1977. Phenol business in changing times. Proc. 83rd
Natl. Meet. Am. Inst. Chem. Eng.
Faith, et al. 1975. Industrial Chemicals. 4th ed. Interscience
Publishers, John Wiley and Sons, Inc., New York.
Jolley, R.L. 1973. Chlorination effects on organic constituents
in effluents from domestic sanitary sewage treatment plants. Ph.D.
dissertation, University of Tennessee, Knoxville.
Jolley, R.L., et al. 1975. Chlorination of cooling water: A
source of environmentally significant chlorine-containing organic
compounds. Proc. 4th Natl. Symp. Radioecology. Corvallis, Oregon.
Kirk, R.E. and D.F. Othmer. 1963. Kirk-Othmer Encyclopedia of
Chemical Technology. 2nd ed. John Wiley and Sons, Inc., New York.
Manufacturing Chemists Assoc. 1964. Chemical safety data sheet
SD-4; Phenol. Washington, B.C.
A-7
-------
Middaugh, D.P. and W.P. Davis. 1976. Impact of Chlorination Proc-
esses on Marine Ecosystems. In; Water quality research of the U.S.
Environ. Prot. Agency. EPA Report No. 600/3-76-079. Washington,
D.C. p. 46.
Mischonsniky, S. 1934. A study of the pollution of fish contain-
ing waters by waste phenolic waters. 14th Congr. Chrm. Ind.
(Paris) Jour. Am. Water Works Assoc. 29: 304.
Neujahr, H.Y. and J.M. Varga. 1970. Degradation of phenols by in-
tact cells and cell-free preparations of Trichosporon cutaneum.
Eur. Jour. Biochem. 13: 37.
Patty, F.A. (ed.) 1963. Industrial Hygiene and Toxicology.
John Wiley and Sons, Inc., New York.
Perel'shtein, E.I. and V.T. Kaplin. 1968. Mechanism of the Self
Purification of Inland Surface Waters by the Removal of Phenol Com-
pounds. II. Effect of Natural uv Rays on Aqueous Solutions of Phe-
nol Compounds. Gidrokhim. Mater. In; Chem. Abstr. 84: 139.
Sax, N.I. 1975. Dangerous Properties of Industrial Materials.
4th ed. Van Nostrand Reinhold Co., New York.
Spector, W.S. 1956. Handbook of Toxicology. W.B. Saunders Co.,
Philadelphia.
A-8
-------
Stecher, P.G. (ed.) 1968. The Merck Index. Merck and Co., Rahway,
New Jersey.
Stom, D.J. 1975. Use of thin-layer and paper chromatography for
detection of ortho- and para- quinones formed in the course of phe-
nol oxidation. Acta Hydrochim. Hydrobiol. 3: 39
Tomkiewicz, M. , et al. 1971. Electron paramagnetic resonance
spectra of semiquinone intermediates observed during the photooxi-
dation of phenol in water. Jour. Am. Chem. Soc. 93: 7102.
Weast, R.C. (ed.) 1974. Handbook of Chemistry and Physics. 55th
ed. CRC Press, Cleveland, Ohio.
Wibaut-Isebree, N.L. 1964. Influence of light on destruction of
phenol in water. Hydrobiol. 24: 540.
A-9
-------
Aquatic Life Toxicology*
INTRODUCTION
Phenol is predominantly used as an intermediate in a wide variety of
chemical processes. These processes produce epoxy and phenolic resins,
Pharmaceuticals, germicides, fungicides, slimicides, herbicides, dyes, and a
variety of industrially important acids. The phenol molecule easily substi-
tutes in the environment to form compounds such as halophenols, which may be
more toxic than the parent molecule. Phenol is degraded by a number of bac-
teria and fungi that may cause slime growths and may depress dissolved oxy-
gen in the receiving waters, thus lowering water quality.
Although an abundance of data on the acute toxicity of phenol to fresh-
water fish and invertebrate species is available, the chronic toxicity data
are limited to one test with the fathead minnow. Toxicity testing with the
same species by different researchers in different waters produced LCcn
values which varied widely. This indicates that parameters such as pH,
hardness, temperature or other water quality characteristics may alter the
toxicity of the compound.
The data base for saltwater species is much more limited with acute data
for three fish and three invertebrate species. No chronic data are avail-
able.
EFFECTS
Acute Toxicity
Toxicity data for eight freshwater invertebrate species, including a
*The reader is referred to the Guidelines for Deriving Water Quality
Criteria 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
-------
rotifer, a snail, cladocerans, and copepods, are listed in Table 1. Tests
conducted by Alekseyev and Antipin (1976) compare the relative sensitivity
of three cladoceran species in the same water using similar test methods.
The LC,-0 values range from 14,000 ug/1 for Daphnia longispina to 57,000
ug/1 for Polyphemus pediculus. Data in Table 1 indicate that a rotifer,
Philodina acuticornis, and two species of copepods are among the least
sensitive. Cairns, et al. (1978) tested phenol at different temperatures
and found little, if any, effect. LC5Q values were in the range from
91,000 to 100,000 yg/1 for Daphnia magna and 79,000 to 93,000 ug/1 for
Daphnia pulex. Anderson, et al. (1948) and Dowden and Bennett (1965) found
young Daphnia magna to be about three times more sensitive than adults.
Acute toxicity data for nine freshwater fish species are included in
Table 1. Rainbow trout was the most sensitive fish species tested with an
LC50 value of 5,020 wg/l (McLeay, 1976). The least sensitive species was
the fathead minnow with LC5Q concentrations as high as 67,500 ug/1 (U.S.
EPA, 1978b). There is a wide range of intraspecific sensitivity in addition
to the wide range of interspecific sensitivity previously mentioned. LC5Q
values for rainbow trout varied from 5,020 ug/1 (McLeay, 1976) to 11,600
ug/1 (Fogels and Sprague, 1977). The fathead minnow, a commonly used test
species, had LC5Q values that varied from 24,000 ug/1 (Ruesink and Smith,
1975) to 67,500 ug/1 (U.S. EPA, 1978b). The bluegill, another commonly used
test species, had LC5Q values from 11,500 ug/1 (Cairns and Scheier, 1959)
to 28,116 ug/1 (Cairns, et al. 1978).
Only four saltwater species have been tested using standard test dura-
tion. Fifty percent effect levels for embryos of the eastern oyster and
hard clam were 58,250 and 52,630 ug/1, respectively (Table 1). The grass
shrimp was much more sensitive with an LCgQ of 5,800 ug/1. The mountain
bass, a species endemic to Hawaii, provided a 96-hour LCrQ value of 11,000
8-2
-------
ug/1 (Table 1). There are too few data to evaluate any effect of environ-
mental variables on toxicity.
Chronic Toxicity
An early life stage test with the fathead minnow (Holcombe, et al. 1980)
produced an estimated maximum acceptable toxicant concentration of 1,830 to
3,570 ug/1 which yields a chronic value of 2,560 ug/1 and an acute-chronic
ratio of 14 (Table 2). Species mean acute values and the acute-chronic ra-
tio are summarized in Table 3.
No chronic effects are available for any saltwater species.
Plant Effects
Reynolds, et al. (1973) conducted a series of tests with an alga, Sele-
nastrum capricornutum, and found at phenol concentrations of 20,000 ug/1
that growth inhibition increased from 12 percent to 32 percent as tempera-
ture increased from 20 to 28°C (Table 4). Reynolds, et al. (1975) found
greater than 50 percent reduction in cell numbers of the same alga at 20,000
ug/1 in 1.92, 2.0, and 2.26 days at 20, 24, and 28°C, respectively. Duck-
weed was considerately less sensitive with an IC™ of 1,504,000 yg/1
(Blackman, et al. 1955) and 50 percent reduction in growth at 479,400 ug/1
(Simon and Blackman, 1953).
Residues
Table 5 contains bioconcentration data on phenol for goldfish. However,
since no maximum permissible tissue concentration is available for phenol,
no Final Residue Value can be calculated. The bioconcentration factors cal-
culated for phenol (Kobayashi, et al. 1976, Kobayashi and Akitake, 1975)
ranged from 1.2 to 2.3. Bioconcentration factors this low indicate that no
residue problem should occur from exposure to phenol.
Miscellaneous
Birge, et al. (1979) conducted tests at hardnesses of 50 and 200 mg/1
B-3
-------
as CaC03 and determined 4-day LC5Q values for three species of fishes
after exposure of the entire embryo stage and four days of the larval life
stage. LC5Q values for rainbow trout were 310 and 70 ug/1, for goldfish,
840 and 340 ug/1, and for bluegills 2,420 and 1,690 yg/1 in soft and hard
water, respectively. The tests indicate that hardness may affect the toxi-
city of phenol although related characteristics may be the factor.
Cairns, et al. (1978) in tests conducted with rainbow trout at 5, 12,
and 18°C calculated 24-hour LC5Q values of 5,600, 11,000, and 11,300 ug/1,
respectively. The tests indicate that rainbow trout are about twice as
sensitive at 5°C than at 12 and 18°C.
Mitrovic, et al. (1968) detected gill damage in rainbow trout juveniles
in 2 hours at a concentration of 6,500 yg/1. However, it is difficult to
understand the environmental significance of this because of possible com-
pensatory reactions in the fish.
Histopathological damage occurred in the saltwater clam, Mercenaria mer-
cenaria, at phenol concentrations of 100 ug/l and higher (Table 6). No
change was observed at 10 yg/1.
The saltwater mountain bass reacted to phenol concentrations as low as
2,000 ug/1, and the 48-hour LC5Q for the rainbow trout in saltwater was
6,900 wg/1 (Table 6).
Summary
The acute toxicity of phenol to freshwater species is expressed over a
range of 2 to 3 orders of magnitude. Of the four families of invertebrate
species represented, the cladocerans were the most sensitive. Acute values
for fish species range from 67,500 ug/1 for fathead minnows to 5,020 ug/1
for juvenile rainbow trout. The acute value for rainbow trout of 5,020 ug/1
and the value of 5,000 ug/1 for Daphnia magna are the lowest acute values
observed.
B-4
-------
A fathead minnow early life stage test resulted in a chronic value of
2,560 ug/1 with an acute-chronic ratio of 14.
Bioconcentration factors ranged from 1.2 to 2.3 in goldfish in five
days. Factors this low indicate that no residue problem should occur from
exposure to phenol.
Only three saltwater invertebrate and three fish species have been stud-
ied as to the acute effects of phenol. LC5Q values were observed as low
as 5,800 ug/1. Histopathological damage was observed in the hard clam at
concentrations as low as 100 ug/1. A saltwater fish reacted to concentra-
tions as low as 2,000 ug/1.
CRITERIA
The available data for phenol indicate that acute and chronic toxicity
to freshwater aouatic life occur at concentrations as low as 10,200 and
2,560 ug/1, respectively, and would occur at lower concentrations among
species that are more sensitive than those tested.
The available data for phenol indicate that acute toxicity to saltwater
aouatic life occurs at concentrations as low as 5,800 ug/1 and would occur
at lower concentrations among species that are more sensitive than those
tested. No data are available concerning the chronic toxicity of phenol to
sensitive saltwater aauatic life.
B-5
-------
Table t. Acute values for phenol
CD
I
Species
Method*
LC50/EC50
(ug/l)
Species Mean
Acute Value
(ug/l) Reference
FRESHWATER SPECIES
Rot 1 f er,
Philodina acuticornls
Snail,
Physa heterostropha
Cladoceran,
Daphnla longlsplna
Cladoceran,
Daphnla magna
Cladoceran,
Daphnla magna
Cladoceran (young),
Daphnla magna
Cladoceran (adult),
Daphnla magna
Cladoceran,
Daphnla magna
Cladoceran,
Daphnla magna
Cladoceran,
Daphnia magna
Cladoceran,
Daphnla magna
C ladoceran,
Daphnla magna
Cladoceran,
Daphnla put ex
s,
s,
R.
s.
s.
s.
s.
s,
s.
s.
s,
s.
s.
u
u
u
u
u
u
u
M
M
M
M
M
U
248,000
94,000
14,000
9,600
11,800
7,000
21,000
100,000
92,000
91,000
88,000
91,200
28,000
248,000 Bulkema, et al. 1974
94,000 Patrick, et al. 1968
14,000 Alekseyev & Antipln,
1976
Kopperman, et al.
1974
U.S. EPA, 1978a
Oowden & Bennett,
1965
Oowden & Bennett,
1965
Cairns, et al. 1978
Cairns, et al. 1978
Cairns, et al. 1978
Cairns, et al. 1978
36,400 Cairns, et al. 1978
Lee, 1976
-------
Table I. (Continued)
CD
i
Species
C ladoceran,
Daphnla pulex
C ladoceran,
Daphnia pulex
C ladoceran,
Daphnla pulex
C ladoceran,
Daphnla pulex
C ladoceran,
Daphnla pulex
C ladoceran,
Daphnla pulex
C ladoceran,
Polyphemus pedlculus
Copepod,
Cyclops vernal Is
Copepod ,
Mesocyclops leukarti
Rainbow trout (juvenile).
Sal mo qairdner i
Rainbow trout (juvenile),
Sal mo galrdneri
Rainbow trout,
Salmo gairdneri
Goldfish,
Carassius auratus
Fathead minnow (adult),
Method*
S, M
s,
s,
s.
s.
R.
R,
s,
s,
R,
FT,
FT,
s,
FT,
M
M
M
M
U
U
U
U
U
M
M
U
M
LC50/EC50
ivo/n
93,000
87,800
85,000
81,000
79,000
18,000
57,000
122,000
108,000
5,020
8,900
11,600
44,490
67,500
Species Mean
Acute Value
(ug/l) Reference
Cairns, et al. 1978
Cairns, et al. 1978
Cairns, et al. 1978
Cairns, et al. 1978
Cairns, et al. 1978
58,100 Alekseyev & Antipln,
1976
57,000 Alekseyev & Antipln,
1976
122,000 Anderson, et al. 1948
108,000 Anderson, et al. 1948
McLeay, 1976
U.S. EPA, 1978b
10,200 Fogels & Sprague,
1977
44,500 Pickering &
Henderson, 1966
U.S. EPA, 1978b
Plmephales promelas
-------
Table 1. (Continued)
03
I
CO
Species
Fathead minnow,
Plmephales promelas
Fathead minnow,
Plmephales promelas
Fathead minnow (adult),
Plmephales promelas
Fathead minnow (adult),
Plmephales promelas
Fathead minnow,
Plmephales promelas
Fathead minnow,
Plmephales promelas
Channel catfish
(juvenl le),
Ictalurus punctatus
Flagfish,
Jordanella floridae
Mosquitoflsh,
Gambusia affinis
Guppy,
Poecilla retlculata
Guppy,
Poecilla reticulata
Bluegill,
Lepomis macrochirus
Bluegil 1 ( juveni le),
Lepomis macrochirus
Bluegi 1 1,
Method*
S, U
s, u
FT, M
FT, M
FT, M
S, U
S, U
FT, M
S. M
S, M
S, U
S, U
R, M
S, U
Species Mean
LC50/EC50 Acute Value
(liq/l) (ug/l)
34,270
32,000
36,000
24,000
28,780
32,000 36,000
16,700 16,700
36,300 36,300
26,000 26,000
31,000
39,190 34,900
13,500
19,300
13,500
Reference
Pickering 4
Henderson, 1966
Pickering &
Henderson, 1966
Ruesink & Smith,
1975
Ruesink & Smith,
1975
Phipps, et al.
Manuscript
Matt son, et al.
1976
Clemens & Sneed, 1959
Fogels & Sprague,
1977
Nunogawa, et al. 1970
Nunogawa, et al. 1970
Pickering &
Henderson, 1966
Patrick, et al. 1968
Trama, 1955
Cairns & Scheier,
Lepomis macrochirus
1959
-------
Table 1. (Continued)
03
I
Species
B 1 ueg ! 1 1 ,
Lepomis macrochirus
Bluegil 1,
Lepomis macrochirus
B 1 ueg i 1 1 ,
Lepomis macrochirus
Mozambique mouthbrooder,
Tilapfa mossambica
Grass shrimp,
Palaemonetes pug to
Eastern oyster,
Crassostrea virgin lea
Hard clam,
Mercenaria mercenarla
Mountain bass,
Kuhlia sandv icens is
Method*
S, U
s, u
S. U
S, M
S, U
S, U
s, u
S, M
LC50/EC50
(lig/D
Species Mean
Acute Value
(lig/D
20,000
11,500
23,880 16,400
19,000 19,000
SALTWATER SPECIES
5,800
58,250
52,630
11,000
5,800
58,200
52,600
11,000
Reference
Cairns 4 Scheier,
1959
Cairns i Scheier,
1959
Pickering &
Henderson, 1966
Nunogawa, et al. 1970
Tatem, et al. 1978
Davis & Hidu, 1969
Davis & Hidu, 1969
Nunogawa, et al. 1970
* S = static, R = renewal, FT = flow-through, U = unmeasured, M = measured
-------
Table 2. Chronic values for phenol (HoIcombe, et al. 1980)
Limits
Species
Fathead minnow,
Plmephales promelas
Method*
FRESHWATER SPECIES
ELS
1,830-
3,570
Chronic Value
(lig/l)
2,560
ELS = ear Iy I Ife stage
DO
I
Acute-Chronic Ratio
Acute Chronic
Value Value
(ug/l) (ug/l)
Fathead minnow, 36,000 2,560
Plmephales promelas
Ratio
14
-------
Table 3. Species mean acute values and acute-chronic ratios for phenol
a
i
ink*
17
16
15
14
13
12
11
10
9
8
7
6
5
4
Species
Rot 1 f er,
Phllodlna acuticornls
Copepod,
Cyclops vernal Is
Copepod,
Mesocyclops leukartf
Snail,
Physa heterostropha
C 1 adoceran ,
Oaphnla pulex
Cl adoceran,
Polyphemus pedlculus
Goldfish,
Car ass 1 us auratus
Cl adoceran,
Daphnla magna
Flagflsh,
Jordanella f lorldae
Fathead minnow,
Plmephales promelas
Guppy,
Poecll la retlculata
Mosqultof Ish,
Gambusla afflnls
Mozambique mouthbrooder,
Tllapla mossamblca
Channel catfish.
Species Mean
Acute Value
(Mfl/l)
FRESHWATER SPECIES
248,000
122,000
108,000
94,000
58,100
57,000
44,500
36,390
36,300
36,000
34,900
26,000
19,000
16,700
Acute-Chronic
Ratio
-
-
-
-
14
-
I eta Iurus punctatus
-------
Table 3. (Continued)
Cd
I
M
to
Rank*
3
2
1
4
3
2
1
Species
Bluegill,
Lepomls macrochlrus
Cladoceran,
Daphnla lonqlspina
Rainbow trout,
Sal mo gairdneri
SALTWATER
Eastern oyster,
Crassostrea virgin lea
Hard clam,
Mercenar I a mercenar la
Mountain bass,
Kuhlla sandvlcensis
Grass shrimp,
Palaemonetes puqio
Species Mean
Acute Value
-------
Table 4. Plant values for phenol
03
I
M
U)
Species
Alga,
Selenastrum caprlcornutum
Alga,
Selenastrum caprlcornutum
Alga,
Selenastrum caprlcornutum
Alga,
Selenastrum caprlcornutum
Alga,
Selenastrum caprlcornutum
Alga,
Selenastrum caprlcornutum
Alga,
Selenastrum caprlcornutum
Duckweed,
Lemna minor
Duckweed,
Lemna minor
Effect
FRESHWATER SPECIES
Result
(ug/D
12$ growth
Inhibition
at 20 C
27$ growth
Inhibition
at 24 C
32$ growth
Inhibition
at 28 C
>50$ reduction
of 1-day steady
state eel I
concentrat Ion
58$ reduction
In eel I numbers
In 1.92 days
at 20 C
66$ reduction
In eel I numbers
in 2.0 days
at 24 C
60$ reduction
in eel I numbers
in 2.26 days
at 28 C
Ch I oros I s
(LC50)
50$ reduction
in growth
20,000
20,000
20,000
40,000
20,000
20,000
20,000
1,504,000
479,400
Reference
Reynolds, et al.
1973
Reynolds, et al.
1973
Reynolds, et al.
1973
Reynolds, et al.
1975
Reynolds, et al.
1975
Reynolds, et al.
1975
Reynolds, et al.
1975
Blackman, et al.
1955
Simon & Blackman,
1953
-------
Table 5. Residues for phenol
Bioconcentration Duration
Species Tissue Factor (days) Reference
Goldfish,
Carassius auratus
Goldfish,
Carassius auratus
Goldfish,
Carassius auratus
FRESHWATER SPECIES
Whole body 2.0
Whole body 2.0
Whole body 1.2-2.3
1 Kobayashl, et al.
1976
5 Kobayashi & Akitake,
1975
5 Kobayashl & Akitake,
1975
DO
I
-------
Table 6. Other data for phenol
W
I
M
01
Species
DI atom,
Nltzschla linear Is
Alga,
ChiorelI a pyrenaldosa
Alga,
Chi ore I la vulgar Is
Parameclum,
Chllomonas paramecium
Parameclum,
Chilomonas paramecium
Parameclum,
Chllomonas paramecium
Rotifer,
Phllodlna acutlcornis
Rotifer,
Ph11odIna acutI corn Is
Rotifer,
Philodlna acutlcornis
Rotifer,
Phllodlna acutlcornis
Rotifer,
PhI Iod i na acutIcorn Is
Annel Id,
Aeolosoma head ley I
Annelid,
Aeolosoma head ley I
FRESHWATER SPECIES
120 hrs
2 days
80 hrs
19-25 hrs
44-48 hrs
98-163 hrs
48 hrs
48 hrs
48 hrs
48 hrs
48 hrs
48 hrs
48 hrs
50$ reduction in
cell production
Comp 1 ete
destruction of
ch lorophy 1 1
20? inhibition
of growth
>50£ decrease in
growth
>50j6 decrease in
growth
>50$ decrease In
growth
LC50
LC50
LC50
LC50
LC50
LC50
LC50
Result
(ug/l) Reference
258,000 Patrick, et al. 1968
1,500,000 Huang & Gloyna, 1968
470,000 Dedonder A Van
Sumere, 1971
200,000 Cairns, et al. 1978
200,000 Cairns, et al. 1978
200,000 Cairns, et al. 1978
300,000 Cairns, et al. 1978
282,000 Cairns, et al. 1978
245,000 Cairns, et al. 1978
205,000 Cairns, et al. 1978
292,000 Cairns, et al. 1978
360,000 Cairns, et al. 1978
351,000 Cairns, et al. 1978
-------
Table 6. (Continued)
03
I
Species
AnnelId,
Aeolosonia headleyi
AnnelId,
Aeolosoma headleyi
AnnelId,
AeoIosoma headleyi
Snail,
Limnaea stagnalIs
Snail,
NltrocrIs sp.
Snal I,
NltrocrIs sp.
Snail,
NltrocrIs sp.
Snail,
NltrocrIs sp.
Snal I,
Nltrocris sp.
Snail (adult),
Physa fontlnalis
Sna11 (juvenile),
Physa fontlnalIs
Clam,
Sphaerlum corneum
Cladoceran,
Daphnia magna
Cladoceran (young),
Daphnia magna
Result
Duration
48 hrs
48 hrs
48 hrs
48 hrs
48 hrs
48 hrs
48 hrs
48 hrs
48 hrs
48 hrs
48 hrs
48 hrs
16 hrs
96 hrs
Effect
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50
Immobi 1 ization
EC50
(ug/i)
381,000
356,000
341,000
350,000
389,000
351,000
353,000
360,000
391,000
320,000
260,000
780,000
94,000
5,000
Reference
Cairns, et al. 1978
Cairns, et al. 1978
Cairns, et al. 1978
Alekseyev 8, Antipin,
1976
Cairns, et al. 1978
Cairns, et al. 1978
Cairns, et al. 1978
Cairns, et al. 1978
Cairns, et al. 1978
Alekseyev i Antipin,
1976
Alekseyev & Antipin,
1976
Alekseyev & Antipin,
1976
Anderson, 1944
Anderson, et al. 194f
-------
Table 6. (Continued)
Species
Effect
Result
(ufl/l) Reference
CO
I
Cladoceran (adult),
Paphnla magna
Conchostracan,
Lynceus brachyurus
Isopod (adult),
Asel lus aquaticus
Isopod ( juvenl le),
Asel lus aquaticus
Rainbow trout,
Sal mo galrdneri
Rainbow trout,
Salmo galrdneri
Rainbow trout,
Salmo galrdneri
Rainbow trout,
Salmo galrdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout (embryo),
Salmo gairdneri
Rainbow trout (embryo),
Salmo gairdneri
Rainbow trout,
Salmo galrdneri
Rainbow trout,
Salmo gairdneri
96 hrs
48 hrs
48 hrs
48 hrs
48 hrs
48 hrs
48 hrs
48 hrs
48 hrs
48 hrs
22 days
22 days
26 days
26 days
EC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50 (hardness =
50 mg/l CaC03)
LC50 (hardness =
200 mg/l CaC03)
LC50 (hardness =
50 mg/l CaC03)
LC50 (hardness =
200 mg/l CaC03)
14,000
78,000
15,000
78,000
10,200
10,400
9,000
9,600
9,500
9,200
330
70
310
70
Anderson, et al. 194<
Alekseyev & Antlpln,
1976
Alekseyev & Antipln,
1976
Alekseyev & Antlpln,
1976
Alexander 4 Clarke,
1978
Alexander 4 Clarke,
1978
Alexander & Clarke,
1978
Alexander & Clarke,
1978
Alexander 4 Clarke,
1978
Alexander 4 Clarke,
1978
Birge, et al. 1979
Birge, et al. 1979
Birge, et al. 1979
Birge, et al. 1979
-------
Table 6. (Continued)
to
I
M
GO
Species
Duration
Effect
Result
(ug/l) Reference
Rainbow trout (juvenile),
Sal mo gairdnerl
Rainbow trout (juvenile),
Salmo gairdneri
Rainbow trout (juvenile),
Salmo gairdneri
Rainbow trout (juvenile),
Salmo gairdnerl
Rainbow trout (yearling),
Salmo gairdnerl
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gairdnerl
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout (juvenile),
Salmo gairdneri
Rainbow trout,
Sa Imo gairdneri
Brook trout (juvenile),
Sa 1 ve 1 1 nus font i na 1 1 s
48 hrs
48 hrs
48 hrs
48 hrs
48 hrs
24 hrs
24 hrs
24 hrs
114 mln
2 hrs
48 hrs
24 hrs
50% morta 1 1 ty
50* mortality
50* mortality
50* mortality
50% mortality
50? mortality
50* mortality
50$ morta 1 i ty
50* mortality
Gill damage
Lowest concentra-
tion which killed
50* or more of
the test fish
Temperature selec-
tion shifted
5,400
8,000
9,800
7,500
9,400
5,600
11,000
11,300
12,200
6,500
10,000
7,500
Brown, et al. 1967b
Brown, et al. 1967b
Brown, et al. 19676
Mltrovic, et al. 1968
Brown & Da (ton, 1970
Cairns, et al. 1978
Cairns, et al. 1978
Cairns, et al. 1978
Herbert, 1962
Mitrovlc, et al. 1968
Shumway & Palensky,
1973
Miller & Ogilvie,
1975
Brook trout (juvenile).
Sal veilnus font)nails
significantly
downward
24 hrs 50* mortality
11,700
Miller & OgiIvie,
1975
-------
Table 6. (Continued)
Species
Duration
Effect
Result
03
I
Goldfish,
Carass 1 us auratus
Goldfish,
Carass 1 us auratus
Goldfish,
Carass 1 us auratus
Goldfish,
Carass 1 us auratus
Goldfish (embryo),
Carass I us auratus
Goldfish (embryo),
Carass 1 us auratus
Goldfish,
Carass 1 us auratus
Goldfish,
Carass 1 us auratus
Goldfish,
Carass 1 us auratus
Golden shiner,
Notemlgonlus crysoleueus
Golden shiner,
Notemlgonius crysoleueus
Fathead minnow (adult),
Plmephales promelas
Fathead minnow (adult),
Plmephales promelas
Fathead minnow (adult),
Plmephales promelas
8 hrs
8 hrs
24 hrs
20-30 hrs
3.5 days
3.5 days
7.5 days
7.5 days
24 hrs
24 hrs
24 hrs
24 hrs
216 hrs
122-127 hrs
LC62
LC67
50% mortal Ity
50? mortal Ity
LC50 (hardness =
50 mg/l CaC03)
LC50 (hardness =
200 mg/l CaC03)
LC50 (hardness =
50 mg/l CaC03>
LC50 (hardness =
200 mg/l CaC03)
LC50
50$ mortal Ity
50$ mortality
5Q% morta 1 i ty
Median lethal
threshold
Median lethal
threhold
• m
33,300
41,600
200,000
40,000-
100,000
1,220
390
840
340
60,000
129,000
35,000
65,340
27,000
22,000
Gersdorff, 1939
Gersdorff & Smith,
1940
Cairns, et al. 1978
Kobayashi & Akitake,
1975
Birge, et al. 1979
Blrge, et al. 1979
Blrge, et al. 1979
Birge, et al. 1979
Kobayashi , et al.
1979
Cairns, et al. 1978
Cairns, et al. 1978
Jenkins, I960
Rueslnk 4 Smith, 1975
Rueslnk & Smith, 1975
-------
Table 6. (Continued)
00
I
NJ
O
Species
Walking catfish,
Cl arias batrachus
Guppy (adult),
Poecl 1 la retlculata
Mol lies (adult),
Molllenesla latlplnna
Mol lies (adult),
Molllenesla latlplnna
B 1 ueg 1 1 1 ,
Lepomls macrochfrus
Blueglll (juvenile),
Lepomls macrochlrus
Blueglll (juvenile),
Lepomls macrochlrus
Blueglll,
Lepomls macrochlrus
Blueglll (embryo),
Lepomls macrochlrus
Blueglll (embryo),
Lepomls macrochlrus
Bluegill,
Lepomls macrochlrus
Bluegl II,
Lepomls macrochlrus
Mozambique mouthbrooder,
Tllapla mossamblca
Duration
48 hrs
30 days
25 hrs
50 hrs
25 hrs
48 hrs
48 hrs
24 hrs
2.5 days
2.5 days
6.5 days
6.5 days
1 mo
Effect
50* mortality
Increase In neuro-
secratory hormone
50* mortality
50* mortality
50* mortality
50* mortality
50* mortality
50* mortality
LC50 (hardness =
50 mg/l CaC03)
LC50 (hardness =
200 mg/l CaC03)
LC50 (hardness =
50 mg/l CaC03)
LC50 (hardness =
200 mg/l CaC03)
Manifest nemos 1-
derosls In the
Result
(M9/I)
31,500
3,120
63,000
22,000
10,000-
15,000
22,200
19,000
60,000
3,340
2,430
2,420
1,690
2,000
Reference
Mukherjee &
Bnattacharya, 1974
Matel & Flerov, 1973
Dowden & Bennett,
1965
Dowden & Bennett,
1965
Dowden & Bennett,
1965
Lammerlng & Burbank,
I960
Turnbul 1, et al. 1954
Cairns, et al. 1978
Binge, et al. 1979
Blrge, et al. 1979
Blrge, et al. 1979
Blrge, et al. 1979
Murachl, et al. 1974
sp leen
-------
Table 6. (Continued)
DO
I
Species Duration Effect
Result
(ug/l) Reference
SALTWATER SPECIES
Hard clam (adult), 24 hrs Cellular damage 100 Fries & Tripp, 1977
Mercenarla mercenarla
Hard clam (adult), 24 hrs No cellular
Mercenarla mercenarla damaqe
10 Fries & Tripp, 1977
Mountain bass, Acute Violent reaction 20,000 Hlatt, et al. 1953
Kuhlia sandvlcensis
Mountain bass. Acute Moderate reaction 2,000 Hlatt, et al. 1953
Kuhlia sandvlcensis
Nehu, 12 hrs LC50
Stolephorus purpureus
Rainbow trout, 48 hrs LC50
Sal mo galrdnerl
510 Nunogawa, et al. 19;
6,900 Brown, et al. 1967a
-------
REFERENCES
Alekseyev, V.A. and B.N. Antipin. 1976. Toxicological characteristics and
symptoms of acute phenol poisoning in some freshwater crustaceans and mol-
lusks. Hydrobiol. Jour. 12: 27.
Alexander, D.6. and R.Mc.V. Clarke. 1978. The selection and limitations of
phenol as a reference toxicant to detect differences in sensitivity among
groups of rainbow trout (Salmo gairdneri). Water Res. 12: 1085.
Anderson, B.G. 1944. The toxicity thresholds of various substances found
in industrial wastes as determined by the use of Daphnia magna. Sewage
Works Jour. 16: 1156.
Anderson, B.G., et al. 1948. The evaluation of aauatic invertebrates as
assay organisms for the determination of the toxicity of industrial wastes.
Am. Pet. Inst. Proj. Final Rep. 51.
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 physiological activity of substituted
phenols. I. Relationships between chemical structure and physiological ac-
tivity. Arch. Biochem. Biophys. 54: 45.
Brown, V.M. and R.A. Dalton. 1970. The acute lethal toxicity to rainbow
trout of mixtures of copper, ohenol, zinc, and nickel. Jour. Fish Biol.
2: 211.
B-22
-------
Brown, V.M., et al. 1967a. The acute toxicity of phenol to rainbow trout
in saline waters. Water Res. 1: 683.
Brown, V.M., et al. I967b. The effect of temperature on the acute toxicity
of phenol to rainbow trout in hard water. Water Res. 1: 587.
Buikema, A.L., Jr., et al. 1974. Evaluation of Philodina acuticornis
(Rotifera) as a bioassay organism for heavy metals. Water Resour. Bull.
10: 649.
Cairns, J., Jr. and A. Scheier. 1959 The relationship of bluegill sunfish
body size to tolerance for some common chemicals. Proc. 13th Ind. Waste
Conf., Purdue Univ. Eng. Bull. 43: 243.
Cairns, J., Jr., et al. 1978. Effects of temperature on aauatic organisms
sensitivity to selected chemicals. Project B-084-VA. Bull. 106. VA. Po-
lyt. Inst. State Univ., Blacksburg, Virginia.
Clemens, H.P. and K.E. Sneed. 1959. Lethal doses of several chemicals for
fingerling channel catfish. U.S. Dept. Inter., Fish Wildl. Spec. Sci. Rep.
Fish. No. 316.
Davis, H.C. and H. Hidu. 1969. Effects of pesticides on embryonic develop-
ment of clams and oysters and on survival and growth of the larvae. U.S.
Dept. Inter., Fish Wildl. Fish. Bull. 67: 393.
Dedonder, A. and C.F. Van Sumere. 1971. The effect of phenolics and rela-
ted compounds on the growth and respiration of Chlorella vulgaris. Z.
Pflanzen. Physio!. 65: 70.
B-23
-------
Dowden, B.F. and H.J. Bennett. 1965. Toxicity of selected chemicals to
certain animals. Jour. Water Pollut. Cont. Fed. 37: 1308.
Fogels, A. and J.B. Sprague. 1977. Comparative short-term tolerance of ze-
brafish, flagfish, and rainbow trout to 5 poisons including potential refer-
ence toxicants. Water Res. 11: 811.
Fries, C.R. and M.R. Tripp. 1977. Cytological damage in Mercenaria merce-
naria exposed to phenol. In: D.A. Wolfe, ed. Fate and effects of petrole-
um hydrocarbons in marine organisms and ecosystems. Pergamon Press, New
York. p. 174.
Gersdorff, W.A. 1939. Effect of the introduction of the nitro group into
the phenol molecule on toxicity to goldfish. Jour. Cell. Comp. Physiol.
14: 61.
Gersdorff, W.A. and I.E. Smith. 1940. Effect of introduction of the hal-
ogens into the phenol molecule on toxicity to goldfish. I. Monochlorophe-
nols. Am. Jour. Pharm. 112: 197.
Herbert, 0. 1962. Toxicity to rainbow trout of spent still liauors from
the distillation of coal. Ann. Appl. Biol. 50: 755.
Hiatt, R. W., et al. 1953. Effects of chemicals on a schooling fish, Kulia
sandvicensii. Biol. Bull. 104: 28.
Holcombe, G.W., et al. 1980. Effects of phenol, 2,4-dimethylphenol,
2,4-dichloro- phenol, and pentachlorophenol on embryo, larval, and
early-juvenile fathead minnows (Pimephalels promelas). (Manuscript).
B-24
-------
Huang, J. and E.F. Gloyna. 1968. Effect of organic compounds on photosyn-
thetic oxygenation. I. Chlorophenol destruction and suppression of photo-
synthetic oxygen production. Water Res. 2: 347.
Jenkins, C.R. 1960. A study of some toxic components in oil refinery ef-
fluents. Ph.D. Thesis. Okla. St. Univ.
Kobayashi, K. and H. Akitake. 1975. Metabolism of chlorophenols in fish.
IV. Absorption and excretion of phenol by goldfish. Nippon Suisan Gak-
kaishi. 41: 1271.
Kobayashi, K., et al. 1976. Studies on the metabolism of chlorophenols in
fish: VI. Turnover of absorbed phenol in goldfish. Bull. Jap. Soc. Sci.
Fish. 42: 45.
Kobayashi, K., et al. 1979. Relation between toxicity and accumulation of
various chlorophenols in goldfish. Bull. Jap. Soc. Sci. Fish. 45: 173.
Kopperman, H.L., et al. 1974. Aqueous chlorination and ozonation studies.
I. Structure-toxicity correlations of phenolic compounds to Daphnia magna.
Chem. Biol. Interact. 9: 245.
Lammering, M.W. and N.C. Burbank. 1960. The toxicity of phenol, o-chloro-
phenol and o-nitrophenol to bluegill sunfish. Eng. Bull. Purdue Univ. Eng.
Ext. Serv. 106: 541.
B-25
-------
Lee, DiR. 1976. Development of an invertebrate bioassay to screen petrole-
um refinery effluents discharged into fresh water. Ph.D. Thesis. VA. Po-
lyt. Inst. and State Univ., Blacksburg, Virginia.
Matei, V.E. and B.A. Flerov. 1973. Effect of subtoxic concentrations of
phenol on the conditioned reflexes of Lebistes reticulatus. Jour. Evol. Bi-
ochem. Physio!. 9: 416.
Mattson, V.R., et al. 1976. Acute toxicity of selected organic compounds
to fathead minnows. EPA-600/3-76-097. U.S. Environ. Prot. Agency.
McLeay, D.J. 1976. Rapid method for measuring acute toxicity of pulpmill
effluents and other toxicants to salmonid fish at ambient room temperature.
Jour. Fish. Res. Board Can. 33: 1303.
Miller, D.L. and D.M. Ogilvie. 1975. Temperature selection in brook trout
(Salve!inus fontinalis) following exposure to DDT, PCB or phenol. Bull. En-
viron. Contam. Toxicol. 14: 545.
Mitrovic, V.V., et al. 1968. Some pathological effects of subacute and a-
cute poisoning of rainbow trout by phenol in hard water. Water Res. 2: 249.
Mukherjee, S. and S. Bhattacharya. 1974. Effect of some industrial pollu-
tants on fish brain chloinesterase activity. Environ. Physio!. Biochem.
4: 226.
Murachi, S., et al. 1974. Relation of hemosiderosis in fish spleen to the
waste from chemical plants. Hiroshima Daigahu Suichikusan Gakubu Kiyo.
13: 207.
B-26
-------
Nunogawa, J.N., et al. 1970. The relative toxicities of selected chemicals
to several species of tropical fish. Adv. Water Pollut. Res., Proc. 5th
Int. Conf.
Patrick, R., et al. 1968. The relative sensitivity of diatoms, snails and
fish to twenty common constituents of industrial wastes. Prog. Fish-Cult.
30: 137.
Phipps, 6.L., et al. The acute toxicity phenol and substituted phenols to
the fathead minnow. (Manuscript).
Pickering, Q.H. and C. Henderson. 1966. Acute toxicity of some important
petrochemicals to fish. Jour. Water Pollut. Control. Fed. 38: 1419.
Reynolds, J.H., et al. 1973. Continuous flow kinetic model to predict the
effects of temperature on the toxicity of oil refinery waste to algae. Eng.
Bull. Purdue Univ. Eng. Ext. Ser. 142: 259.
Reynolds, J.H., et al. 1975. Effects of temperature on oil refinery waste
toxicity. Jour. Water Pollut. Control Fed. 47: 2674.
Ruesink, R.G. and L.L. Smith, Jr. 1975. The relationship of the 96-hour
LCgg to the lethal threshold concentration of hexavalent chromium, phenol,
and sodium pentachlorophenate for fathead minnows (Pimephales promelas Raf i-
nesaue). Trans. Am. Fish. Soc. 3: 567.
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.
B-27
-------
Simon, E.W. and G.E. Blackman. 1953. Studies in the principles of phyto-
toxicity. IV. The effects of the degree of nitration on the toxicity of
phenol and other substituted benzenes. Jour. Exp. Bot. 4: 235.
Tatem, H.E., et al. 1978. The toxicity of oils and petroleum hydrocarbons
to estuarine crustacean. Estuarine Coastal Mar. Sci. 6: 365.
Trama, F.B. 1955. The acute toxicity of phenol to the common bluegill (Le-
pomis macrochirus Rafinesoue). Notulae Naturae. 269: 1.
Turnbull, H., et al. 1954. Toxicity of various refinery materials to fresh
water fish. Ind. Engin. Chem. 46: 324.
U.S. EPA. 1978a. In-depth studies on health and environmental impacts of
selected water pollutants. Contract No. 68-01-4646.
U.S. EPA. 1978b. Effects of aoueous effluents from in situ fossil fuel
processing technologies on aauatic systems. Contract No. 77-C-04-3913.
B-28
-------
Mammalian Toxicology and Human Health Effects
INTRODUCTION
Phenol is a high-volume industrial chemical which is widely
used as an intermediate in the manufacture of other chemicals.
Phenol is also produced by biological processes and is a by-product
of combustion and some industrial processes.
Phenol exists at 25°C as a clear, colorless, hygroscopic,
deliquescent, crystalline solid which may become slightly pink in
color as a result of impurities (Lederman and Poffenberger, 1968).
The chemical and physical characteristics of phenol are presented
in Table 1.
Phenol has a long history of industrial and medical use. In
1867, Lister reported on the use of phenol sprays for disinfecting
operating rooms. Today its medicinal uses are limited to a few
mouth, throat, and skin medications. The industrial capacity for
the production of phenol in the United States was 2,885 x 106
pounds per year in 1975 (Anonymous, 1975); about 90 percent of the
phenol produced that year was used in the production of phenolic
resins, caprolactam, bisphenol-A, alkylphenols, and adipic acid
(Chemical Profiles, 1972). Phenol is highly soluble in water under
ambient conditions.
It should be noted that analytical data for phenol should be
interpreted with caution. Many spectrophotometric tests, specific-
ally those following the methodologies presented by Deichmann
(1942) are positive for phenol as well as a spectrum of substituted
phenol compounds (Am. Pub. Health Assoc., 1971; Ettinger, et al.
1951; Smith, 1976).
C-l
-------
TABLE 1
Chemical and Physical Properties of Phenol*
Formula:
Molecular weight:
PKa:
Melting point:
Boiling point:
Vapor pressure @ 25°C
Specific gravity: solid @ 25°C
liquid @ 25°C
Relative vapor density: (air = 1.0)
Solubility: (X = mole fraction)
Phenol in water: -log X =
0.375 log(66 - T) + 1.15.
Water in phenol: -log X =
-0.62 log(66 - T) + 0.99
Color:
Odor:
Flashpoint: open cup
closed cup
Ignition temperature:
Light sensitivity:
Saturated vapor concentration (25°C)
C6H5OH
94.11
9.9
40-41°C
181.75°C
0.35 mm Hg
1.071
1.049
3.24
Also soluble in ether,
alcohol, acetic acid,
glycerol, liquid sul-
fur dioxide, benzene.
Colorless to light
pink solid
Sweet; threshold = Ippm
85°C
79°C
715°C
Darkens on exposure
to light
461 ppm
*Source: NIOSH, 1976
C-2
-------
The National Organic Monitoring Survey (U.S. EPA, 1977) re-
ported finding unspecified concentrations of phenol in 2 out of 110
raw water supplies. The survey found no phenol in any finished wa-
ter supplies. The National Commission on Water Quality (1975) re-
ported from U.S. Geological Survey data that the annual mean con-
centration of phenol in the lower Mississippi River was 1.5 yg/1,
with a maximum of 6.7 yg/1 and a minimum of 0.0 yg/1. The Inter-
national Joint Commission (1978) reported finding <0.5 to 5 yg/1
phenol in the Detroit river between 1972 and 1977.
Phenol is also produced endogenously in the mammalian intesti-
nal tract through the microbial metabolism of 1-tyrosine and
p-hydroxybenzoic acid (Harborne, 1964). In addition, exposures to
benzene (Docter and Zielhuis, 1967) and the ingestion of certain
drugs (Fishbeck, et al. 1975) can lead to increased phenol produc-
tion and excretion.
EXPOSURE
Ingestion from Water
As noted previously, during the National Organic Monitoring
Survey (U.S. EPA, 1977), phenol was found in only 2 of 110 raw water
supplies analyzed by gas-liquid chromatography and mass spectro-
metry; however, in the two instances in which the presence of
phenol was detected, no quantification was made. No phenol was
found in finished water supplies. The National Commission on Water
Quality (1975) reported an annual mean concentration of 1.5 yg/1 of
phenol in raw water from the lower Mississippi River. At a water
intake of 2 liters per day, this would result in a phenol intake of
3 yg/person/day.
C-3
-------
A 1974 train derailment in southern Wisconsin resulted in sig-
nificant groundwater contamination by phenol (Delfino and Dube,
1976; Baker, et al. 1978). Most families in the area of the spill
continued drinking their well water until it became unpalatable.
The maximum concentration of phenol in the contaminated water actu-
ally ingested by the 39 victims is uncertain. The first tests
revealed phenol concentrations of 0.21 to 3.2 mg/1 in nearby wells.
Concentrations in the well water eventually reached a maximum of
1,130 mg/1. Baker, et al. (1978) estimated exposures of 10 to
240 mg/person/day in the highest exposure group. Medical histories
taken six months after the spill showed a statistically significant
increase in reported cases of diarrhea, mouth sores, dark urine,
and burning of the mouth. Laboratory tests done at this same time
for serum glutamic oxalacetic transaminase (SCOT), bilirubin,
creatinine, uric acid, glucose, and cholesterol showed no signifi-
cant abnormalities. Six months after each group's initial expo-
sure, urinary free and conjugated phenol levels were 11.97 mg/1 for
the study group and 11.56 mg/1 for the control group, indicating
that the metabolism of dietary constituents, rather than the inges-
tion of contaminated water, contributed to the phenol found in the
urine at that time.
Prior to 1900, phenol was frequently ingested to commit sui-
cide (von Oettingen, 1949). Reported lethal doses in man ranged
from 4.8 to 128.0 grams [National Institute for Occupational Safety
Health (NIOSH), 1976j.
C-4
-------
Ingestion from Food
Free and conjugated phenol are normal constituents of animal
matter (Table 2) . They are most likely formed in the intestinal
tract by microbial metabolism of 1-tyrosine and p-hydroxybenzoic
acid (von Oettingen, 1949; Harborne, 1964). There are no market
basket surveys of free and conjugated phenol to allow an estimate
of the daily dietary intake of phenol. Lustre and Issenberg (1970)
have reported finding 7 mg phenol/kg in smoked summer sausage and
28.6 mg/kg in smoked pork belly.
Four medicinal preparations which could be expected to con-
tribute to the ingestion of phenol are presently on the market.
They are Cepastat® Mouthwash and Cepastai® Lozenges, containing
1.45 percent phenol; Chloraseptic® Mouthwash, containing 1.4 per-
cent phenol; and Chloraseptic® Lozenges, containing 32.5 mg total
phenol (free phenol and sodium phenolate) per lozenge with a total
manufacturer's recommended dose of up to eight lozenges per day
(Huff, 1978). Because there is no control over the intake of non-
prescription drugs, some individuals may consume considerably
higher doses.
The taste and odor of phenol, and particularly of some of its
derivatives, are noticeable at relatively low concentrations
(Table 3) .
In a study conducted at the Mellon Institute in Pittsburg,
Pennsylvania, by Hoak (1957), a panel of 2 or 4 persons sniffed
samples of pure phenolic compounds in odor-free water, which had
been heated to 30 to 60°C. A flask of plain odor-free water was
provided for comparison. The various samples were placed in random
C-5
-------
Tissue
TABLE 2
Phenol Content of Normal Rabbit Tissues*
(6 animals)
Free
Phenol (mg/kg)
Conjugated
Total
Blood
CNS
Kidney
Lung
Liver
Muscle
G.I. Tract (includ-
ing contents)
Heart, spleen, thymus,
testes, adrenals
Urine (24 hr. vol.)
Feces (24 hr.)
0-0.7
0
0-1.0
0-2.3
0-0.9
0-1.6
0-3.0
0-0.3
0-3.9
0.4-5.3
0-0.5
0-1.8
0-0.5
0-3.4
1.1-5.5
0-1.8
0-2.3
0-1.0
11.5-100.0
1.4-8.0
0-0.7
0-1.8
0-1.4
0-3.4
1.1-6.2
0-3.4
0-4.4
0-1.0
11.5-100.0
1.8-11.7
*Source: Deichmann, 1944.
C-6
-------
TABLE 3
Taste and Odor Thresholds for Phenol in Water
Taste Odor Temperature Reference
mg/1 mg/1 °C
>1.0 >1.0 ca.24 Burttschell,
et al. 1959
°-3 4-0 20-22 Dietz and Traud,
1978
60 - Campbell, et al.
1958
10-0 30 Hoak, 1957
5-° 60 Hoak, 1957
1.0 1.0 - Veldrye, 1972
C-7
-------
order before the test persons, and the flask with the lowest per-
ceptible odor was noted by each individual sniffer. The lowest
concentration detected was considered to be the threshold. Of the
chemicals tested, chlorinated phenols were the compounds most
easily detected. The odor thresholds reported for phenol were 10
yg/1 at 30°C and 5 ug/1 at 60°C. Hoak (1957) speculated that odor
should be expected to become more noticeable as temperature in-
creases; however, in evaluating phenol and a series of chloro-
phenols and cresols, it was found that some compounds had higher
odor thresholds at 30°C, while others were higher at 60°c.
Burttschell, et al. (1959) made dilutions of phenolic com-
pounds in carbon-filtered tap water and used a panel of from 4 to 6
persons to evaluate odor and taste. Tests were carried out at room
temperature, which the investigator estimated to be 25°C. If a
panel member's response was doubtful, the sample was considered
negative. The geometric means (>-1,000 yg/1 for odor and taste) of
the panel responses were used as the organoleptic thresholds. The
data presented did not indicate a range of responses.
Campbell, et al. (1958) studied the taste thresholds of six
odor-producing chemicals including phenol. Solutions of the chemi-
cals were prepared using redistilled water. Panels of 21 to 22
experienced judges participated in different organoleptic tests of
the triangle type. Concentrations of chemicals chosen for the tri-
angle tests were such that the odd sample would be identified by
more than 35, but less than 100 percent of the judges. Samples were
served in 25 ml portions, and the judges were asked only to iden-
C-8
-------
tify the odd sample. When 50 percent of the judges correctly sepa-
rated the samples in a given triangle test, the concentration of
compound used in that test was considered to be the threshold
level. Although a number of judges were able to detect the pres-
ence of phenol at a concentration of 14 mg/1, a threshold level of
60 mg/1 was reported based upon the experimental methodology used.
Dietz and Traud (1978) used a panel composed of 9 to 12 per-
sons of both sexes and various age groups to test the organoleptic
detection thresholds for 126 phenolic compounds. To test for odor
thresholds, 200 ml samples of the different test concentrations
were placed in stoppered odor-free glass bottles, shaken for
approximately five minutes, and sniffed at room temperature (20 to
22 C). For each test, water without the phenolic additive was used
as a background sample. The odor tests took place in several 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 tasted water samples containing various amounts of
phenolic additives. As a point of comparison, water without
phenolic additives was tasted first. Samples with increasing
phenolic concentrations were then tested. Between samples, the
mouth was rinsed with the comparison water and the test person ate
several bites of dry white bread to "neutralize" the taste. Geo-
metric mean detection level values for both tests provided thresh-
old levels of phenol of 0.3 mg/1 for taste and 4.0 mg/1 for odor.
C-9
-------
None of the four organoleptic studies described, however,
indicated whether the determined threshold levels made the water
undesirable or unfit for consumption.
A bioconcentration factor (BCF) relates the concentrations 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 consumption of fish and shellfish, the weighted average per-
cent 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,
1980a). These data were used to estimate that the per capita 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
lipids for consumed freshwater and estuarine fish and shellfish is
3.0 percent.
Measured BCFs of 1.2 to 2.3 were obtained with goldfish by
Kobayashi, et al. (1976) and Kobayashi and Akitake (1975), but per-
cent lipids was not measured. The equation "Log BCF = (0.85 Log
P) - 0.70" can be used (Veith, et al. 1979) to estimate the BCF for
aquatic organisms that contain about 7.6 percent lipids (Veith,
1980) from the octanol/water partition coefficient (P) . Based on
C-10
-------
an average measured log P value of 1.48 (Hansch and Leo, 1979), the
steady-state BCF for phenol is estimated to be 3.6. 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 average BCF for phenol and the
edible portion of all freshwater and estuarine aquatic organisms
consumed by Americans is calculated to be 3.6 x 0.395 = 1.4.
Inhalation
The inhalation of phenol vapors appears to be largely re-
stricted to the occupational environment. Phenol vapor is effi-
ciently absorbed from the lungs. Piotrowski (1971) administered
phenol vapors to human volunteers wearing masks to minimize the ef-
fect of skin absorption. The phenol concentrations ranged from 6
to 20 mg/m . Piotrowski (1971) found that the retention of phenol
averaged 80 percent at the beginning of the exposure but decreased
to an average retention of 70 percent after eight hours of expo-
sure. He did not report any adverse effects in his subjects after
the exposures to phenol vapor.
Ohtsuji and Ikeda (1972) found up to 12.5 mg/m3 of phenol va-
pors in bakelite factories. They reported no adverse effects but
confirmed that phenol was efficiently absorbed through the lungs.
The present threshold limit value (TLV) for phenol is 20 mg/m3
as a time-weighted average (TWA) with a ceiling value of 60 mg/m3
(NIOSH, 1976).
Dermal
The primary site of phenol absorption in industrial exposures
is the skin. The skin is a major route of entry for phenol vapor,
C-ll
-------
phenol solutions, liquid phenol, or solid phenol. Piotrowski
(1971) determined that the rate of absorption of phenol vapor
through the skin was similar to that through the respiratory tract.
Aqueous phenol solutions (1 percent w/v) readily penetrate human
skin (Roberts, et al. 1977). As the phenol concentration in-
creases, the permeability coefficient also increases. At very high
concentrations of phenol in water, the resulting skin damage re-
tards the absorption of phenol (Deichmann and Keplinger, 1963).
In addition to exposures from occupational sources, a number
of medicinal preparations can be sources of dermally absorbed phe-
nol. A partial census of phenol-containing preparations for skin
(R)
application is as follows: Campho-Phenique—' liquid - 4.75 percent
phenol, powder - 2 percent; Calamine lotion, 1 percent phenol;
ointment or liquid, 1 percent phenol; Panscoi-' ointment, 1 percent
phenol; Benadex^ ointment, 1 percent phenol; Kip for Burns-' oint-
ment, 0.5 percent phenol; Noxzema Medicated Cream-', 0.5 percent
phenol; Tanuror^ ointment, 0.75 percent phenol; Dri ToxeiW cream,
1 percent phenol; Peterson's ointment-^, 2.5 percent phenol. The
quantities of these drugs used are not under control. In addition,
some feminine hygiene products and hemorrhoidal products contain
phenol (Huff, 1978; Am. Pharm. Assoc. 1977).
PHARMACOKINETICS
Absorption
Phenol is readily absorbed by all routes of entry. Absorption
is rapid, as illustrated by the fact that acutely toxic doses of
phenol can produce symptoms within minutes of administration, re-
gardless of the route of administration.
C-12
-------
As noted earlier in this document, Piotrowski (1971) exposed
human volunteers in climate-controlled inhalation chambers to phe-
nol administered through face masks to eliminate the influence of
dermal exposure. He found that, initially, an average of 80 per-
cent of the phenol was retained in the lungs. The percentage of
retained phenol dropped during the experiment, so that after 6 to 8
hours an average of only 70 percent of the inhaled phenol was re-
tained in the lungs. Subsequently, Piotrowski (1971) exposed his
volunteers for 6 to 8 hours to various phenol concentrations in the
exposure chamber atmosphere, while permitting them to breathe clean
air through the face masks. He found that phenol vapor could be
readily absorbed through the intact skin and that normal clothing
provided little or no protective effect. He found that the rate of
dermal absorption of phenol vapor could be represented by the for-
mula A=(0.35)C, where A equals the amount of phenol absorbed in
mg/hr, and C is the phenol concentration in mg/m .
When the data presented by Ohtsuji and Ikeda (1972) (see Inha-
lation section) are recalculated utilizing the efficiency of inha-
lation data and the skin absorption coefficient reported by Pio-
trowski, the figures presented may be confirmed.
Distribution
Phenol is rapidly distributed to all tissues in animals that
have been poisoned with the compound. Within 15 minutes of an oral
dose, the highest concentrations are found in the liver, followed
by heart, kidneys, lungs, blood, and muscle (Deichmann, 1944)
(Table 4). As time progresses, concentrations become fairly uni-
form and start to decrease as the body begins to clear the phenol;
C-13
-------
TABLE 4
Distribution of Phenol in the Organs of Rabbits After an
Oral Dose of 0.5 g/kg
Tissue
Phenol
Died
after
15 min.
Died
after
82 min.
Concentration of
Liver
Blood
Kidneys
Lungs
Heart,
Thymus,
Testes,
Spleen
Brain &
Cord
Muscle
Urine
Exhaled
air
Free
Conjugated
Total**
Free
Conjugated
Total
Free
Conjugated
Total
Free
Conjugated
Total
Free
Conjugated
Total
Free
Conjugated
Total
Free
Conjugated
Total
Free
Conjugated
Total
Free
Conjugated
Total
63.7
0.9
64.6
30.8
0.9
31.7
35.3
0.8
36.1
34.2
1.8
36.0
53.0
0.6
53.6
31.3
0.5
31.8
19.0
0
19.0
no sample
0
0
22.4
4.2
26.6
22.4
5.3
27.7
13.4
7.4
20.8
20.8
4.7
25.5
21.0
2.3
23.3
8.2
0.5
8.7
0.5
14.0
14.5
0.1*
0.1
Killed
after
2 hrs.
Phenol in
3.4
3.2
6.6
5.8
8.0
13.8
4.8
22.8
27.6
5.4
6.7
12.1
6.8
5.7
12.5
6.8
0.7
7.5
9.2
1.1
10.3
no sample
0.7*
0.7
Killed
after
2k hrs.
mg/100 g
13.5
6.0
19.5
11.3
10.2
21.5
11.2
12.9
24.1
12.2
5.1
17.3
14.0
5.1
19.1
10.4
0.3
10.7
12.0
0.8
12.8
11.6
52.0
63.6
0.1*
0.1
Killed
after
6 hrs.
tissue
0.5
9.4
9.9
6.5
9.8
16.3
2.6
30.0
32.6
1.5
3.0
4.5
7.5
7.7
15.2
2.5
0.4
2.9
10.1
1.4
11.5
11.0
12.3
23.3
0.2*
0.2
aSource: Adapted from Deichmann, 1944.
*Phenol in total air exhaled.
**Total phenol obtained by summation of free and conjugated fractions,
C-14
-------
the concentrations of total phenol in the kidney remain relatively
constant for the first six hours after oral dosing. In rabbits,
roughly 77 percent of the administered dose is excreted in the
urine during the first 24 hours, and about 20 percent is completely
metabolized. In summary, the distribution of phenol presents a
rapid absorption phase, followed by rapid generalized distribution
to all organ systems, followed by relatively rapid metabolism and
excretion.
The data of Piotrowski (1971) similarly indicate a rapid rate
of clearance of phenol in man, even though his study did not pro-
vide distributional data for various organs.
Metabolism
Free and conjugated phenol appear to be normal trace consti-
tuents of the human body and have also been found in other mam-
malian species (Harborne, 1964). Values reported for phenol con-
centrations in normal human blood differ markedly among various in-
vestigators. Ruedemann and Deichmann (1953) reported normal blood
values to be 1.5 mg/1 for free phenol and 3.5 mg/1 for conjugated
phenol. In a brief list of "normal" human blood values, NIOSH
(1976) cites ranges for free phenol of from none or traces to
40 mg/1 and lists conjugated phenol concentrations ranging from 1
to 20 mg/1. The variability appears to be due in part to the
specificity of the analytical method used to detect phenol (Ikeda
and Ohtsuji, 1969) and to the amount of dietary protein which in-
creases urinary phenol excretion (Folin and Denis, 1915). More re-
cent values determined by gas-liquid chromatography are 0.04 to
0.56 mg/1 for free phenol, 1.06 to 5.18 mg/1 for conjugated phenols
C-15
-------
(Dirmikis and Darbre, 1974), and 2 to 18 mg/1 for total phenol
(Van Haaften and Sie, 1965).
The urinary excretion of phenol can be increased above back-
ground levels by exposure to agents which are normally metabolized
to phenol, such as benzene or phenylsalicylate (Kociba, et al.
1976). The urinary excretion levels of phenol in a worker exposed
to phenylsalicylate ranged from 150 to 1,371 mg/1. The ingestion
of manufacturer's recommended dosages of Pepto-BismoiS' (contains
phenylsalicylate) resulted in peak urinary phenol levels of
260 mg/1 in a human volunteer (Fishbeck, et al. 1975). The normal
background concentration for urinary phenol in this series was 1.5
to 5 mg/1, as detected by gas chromatography. After the ingestion
of eight doses of Chloraseptic**' lozenges at the recommended dosing
schedule, the total urinary phenol concentration peaked at
270 mg/1, and the free phenol concentration peaked at 10 mg/1.
When dogs were fed 125 mg phenylsalicylate/kg body weight/day for
41 days, the peak urinary phenol concentration was 6,144 mg/1.
This treatment was not associated with any reported ill effects
(Kociba, et al. 1976).
The metabolism of exogenous phenol has been most clearly pre-
sented by Deichmann and Keplinger (1963) for a lethal oral dose of
0.5 g/kg body weight in rabbits and for a sublethal oral dose of
0.3 g/kg body weight in rabbits. These studies are summarized in
Figures 1 and 2.
There are some species differences in the metabolism of phe-
nol. Capel, et al. (1972) reported that man, rat, mouse, jerboa,
gerbil, hamster, lemming, and guinea pig excreted four major
C-16
-------
Rabbit
Oral Dose
0.5 g/kg.
Oxidized in
body to C02
and water
plus traces of
1,4-dihydroxy-
benzene and
orthodihy-
droxybenzene
Excreted
in urine
X
Remaining
in carcass
Exhaled
in air
Trace
Excreted
in feces
37%
Excreted as
free phenol
63%
Excreted as
conjugated phenol
FIGURE 1
Fate of a Lethal Oral Dose of Phenol Analyzed Over 5 Hours
Source: Deichmann and Keplinger, 1963
C-17
-------
23%
^-
Oxidized in
body to C02
and water
plus traces of
1,4-dihydroxy-
benzene and
orthodihy-
droxybenzene
Excreted
in urine
Rabbit
Oral Dose
0.3 g/kg
Trace \ 1%
Remaining Exhaled Excreted
in carcass in air in feces
48%
Excreted as
free phenol
50%
Conjugated
with
sulfuric acid
52%
Excreted as
conjugated phenol
30%
Conjugated
with
glucuronic acid
20%
Conjugated
with
other acids
FIGURE 2
Fate of a Sublethal Oral Dose of Phenol Analyzed over 24 Hours
Source: Deichmann and Keplinger, 1963
C-18
-------
metabolites: sulfate and glucuronic acid conjugates of phenol and
of 1,4-dihydroxybenzene. The squirrel monkey and the capuchin mon-
key excreted phenyl glucuronide, 1,4-dihydroxybenzene glucuronide,
and phenyl sulphate. The ferret, dog, hedgehog, and rabbit ex-
creted phenyl sulfate, 1,4-dihydroxybenzene sulfate, and phenyl
glucuronide. The rhesus monkey, fruit bat, and chicken excreted
phenyl sulfate and phenyl glucuronide but not 1,4-dihydroxybenzene
conjugates. The cat appeared to excrete only phenyl sulfate and
1,4-dihydroxybenzene sulfate, and the pig was found to excrete
phenylglucuronide as its major metabolite of phenol. The doses
used in this study were relatively low. Miller, et al. (1976)
demonstrated that the cat was sensitive to phenol; in addition to
sulfate conjugates, free 1,4-dihydroxybenzene was found to be a
major metabolite, possibly accounting for the toxicity observed in
the cat. The authors also noted that the metabolic pattern was
dose dependent. Oehme and Davis (1970) found that with the excep-
tion of cats, the rate of phenylglucuronide excretion increased
progressively with the dose, so that at high doses phenylglucuro-
nide formation predominated over phenyl sulfate formation.
In man, the rate of absorption, metabolism, and excretion of
phenol is relatively rapid. Pietrowski (1971) noted that absorbed
phenol was almost completely metabolized and excreted within
24 hours in inhalation experiments near the TLV.
Excretion
In man and all mammals that have been tested, nearly all of
the phenol and its metabolites are excreted in the urine. Only mi-
nor amounts are excreted in air and in the feces (Deichmann and
C-19
-------
Keplinger, 1963). Piotrowski (1971) studied the excretion of
phenol in human volunteers who had been exposed to phenol through
inhalation or skin absorption. He found that the human body be-
haved almost like a single compartment with respect to phenol
absorption and clearance, with an excretion rate constant of K=0.2
hr . This corresponds to a half-life of approximately 3.5 hours
(Figures 3 and 4). The half-life is defined as
M, - °-693 •
' K
Twenty-four hours after administering 300 mg phenol/kg body
weight orally to rabbits, Deichmann (1944) reported finding less
than 1 percent of the administered dose in the feces.
EFFECTS
Acute, Subacute, and Chronic Toxicity
Regardless of the route of administration, the signs and/or
symptoms of acute toxicity in man and experimental animals are sim-
ilar. The predominant acute action of a toxic dose in man appears
to be on the central nervous system, leading to sudden collapse and
unconsciousness. In some mammalian species, these effects are pre-
ceeded by muscular twitchings and severe convulsions. Mukhitov (as
cited in the 1976 NIOSH Criteria Document on Phenol) reported that
three humans experienced an increased sensitivity to light after
six 5-minute exposures to vapor containing 0.0155 mg phenol/m3.
Four additional subjects responded through the formation of condi-
tioned cortical reflexes after 15-second exposures to 0.024 mg/m3,
and 3 out of 4 subjects responded after 15-second exposures to
0.0155 mg/m . The significance of these findings is questionable
and unknown.
C-20
-------
EXPOSURE TO
PHENOL VAPOUR
120
16 20 24 4 8
Time of day (hr)
12 16 20 24
8
FIGURE 3
Concentrations and excretion rates of phenol in urine in a
subject exposed to phenol vapor in a concentration of 18.3 mg/m3 by
inhalation.
Source: Piotrowski, 1971
C-21
-------
1.2-i
0 2 4 6 8 10 12 14 16 18 20 22 24
Hours from start of exposure
FIGURE 4
Excretion Rate of "Excess" Phenol in Relation to Absorption.
Means + S.D. Dotted Line - Theoretical Curve for K=0.2 Hour"
Source: Piotrowski, 1971
C-22
-------
After the absorption of an acutely toxic dose, the heart rate
first increases and then becomes slow and irregular. After an ini-
tial rise, the blood pressure falls significantly. Salivation may
be evident. There is usually a slight fall in body temperature,
and a marked depression in respiration occurs. Death may occur
within minutes of the acute exposure and is usually due to respira-
tory arrest (Deichmann and Keplinger, 1963; Sollmann, 1957). The
approximate lethal doses (LD5Q) for phenol in various species ex-
posed by several different routes are listed in Table 5. It can be
noted that most of the data fall within one order of magnitude. The
cat appears to be the most sensitive species, which seems to be a
consequence of its metabolism of phenol. It is difficult to esti-
mate the LE>5Q for oral exposure to phenol for man, even though
phenol has a long history of use in suicidal attempts. A series of
human data is presented in Table 6. Dosages were calculated assum-
ing a bodyweight of 70 kg.
When the data in Tables 5 and 6 are compared, it becomes evi-
dent that man is not unusually sensitive to the acute effects of
phenol when compared to other mammalian species.
Deichmann and Keplinger (1963) describe the following patho-
logical changes associated with acute exposures to phenol:
The pathological changes produced by phenol in animals
vary with the route of absorption, vehicle employed, con-
centration, and duration of exposure. Local damages to
the skin include eczema, inflammation, discoloration,
papillomas, necrosis, sloughing, and gangrene. Follow-
ing oral ingestion, the mucous membranes of the throat
and esophagus may show swelling, corrosions, and necro-
ses, with hemorrhage and serious infiltration of the sur-
rounding areas. In a severe intoxication, the lungs may
show hyperemia, infarcts, bronchopneumonia, purulent
bronchitis, and hyperplasia of the peribronchial tis-
sues. There can be myocardial degeneration and necrosis.
C-23
-------
TABLE 5
The Acute Toxicity of Phenol3 to Nonhuman Mammals
Species
Cat
Cat
Dog
Guinea
Pig
Mouse
Rabbit
Rabbit
Rabbit
Rabbit
Rabbit
Rat
Rat
Rat
Rat
Rat
Rat
Route
Subcut.
Oral
Oral
Subcut.
Subcut.
I.V.
Subcut.
Oral
Oral
I. P.
Subcut.
Oral
Oral
I. P.
Dermal
Dermal
LD50
(gAg)
0.09
0.1
0.5
0.68
0.3
0.18
0.5-0.6
0.6
0.4-0.6
0.5-0.6
0.45
0.53
0.34 (20% emuls.)
0.25 (In olive oil)
2.5
0.67
Reference
Tollens, 1905
Macht, 1915
Macht, 1915
Duplay & Cazin, 1891
Tollens, 1905
Deichmann & Wither up,
Tauber, 1895; Tollens
Clarke & Brown, 1906
Deichmann & Witherup,
Deichmann & Witherup,
Deichmann & Witherup,
Deichmann & Witherup,
Deichmann & Witherup,
1944
, 1905
1944
1944
1944
1944
1944
Farquharson, et al. 1958
Deichmann & Witherup,
Conning & Hayes, 1970
1944
In dilute aqueous solution, unless noted otherwise.
C-24
-------
TABLE 6
Oral Toxicity of Phenol in Humans
Total Dose
(g)
5
10-20
15
15
25-30
50
53
Estimated*
(g/kg)
0.07
0.14-0.29
0.21
0.21
0.36-0.43
0.71
0.75
Effect
Survived
Died
Survived
Died
Died
Survived
Survived
Reference
Willhard, 1886
Stajduhar-Caric
Model, 1889
Kronlein, 1873
Geill, 1888
Geill, 1888
Bennett, et al.
, 1968
1950
*assuming a 70 kg bodyweight.
C-25
-------
The 'hepatic cells may be enlarged, pale, and coarsely
granular with swollen, fragmented, and pyknotic nuclei.
Prolonged administration of phenol may cause parenchyma-
tous nephritis, hyperemia of the glomerular and cortical
regions, cloudy swelling, edema of the convoluted tu-
bules, and degenerative changes of the glomeruli. Blood
cells become hyaline, vacuolated, or filled with gran-
ules. Muscle fibers show marked striation.
In addition to the above-mentioned effects, the urine is usu-
ally dark or "smoky" in appearance, probably due to oxidation prod-
ucts of phenol. The urine may darken further upon standing (Soll-
mann, 1957).
The symptoms reported by humans who had consumed phenol-con-
taminated groundwater for approximately one month (Baker, et al.
1978) are summarized in Table 7. The daily dose of phenol consumed
was estimated to be 10 to 240 mg.
Deichmann and Oesper (1940) administered phenol to rats in
their drinking water for 12 months at 0, 800, 1,200, 1,600, 2,000,
and 2,400 mg/1 concentrations. This corresponded to an average
daily intake of 0, 21, 30, 49, 56, and 55 mg, respectively, of
phenol per rat based on actual water consumption data. At the end
of the experiment, there were no significant differences in tissue
phenol levels between the control and experimental rats. The
weight gain of the rats at the two highest dose levels was de-
pressed. A daily oral dose of 56 mg/rat is approximately 30 per-
cent of the single oral dose required to kill a large proportion of
rats in a short time. An additional indication of the rapid
metabolism of phenol is the fact that the rats that ingested the
C-26
-------
TABLE 7
Symptom Distribution of Cases and Controls After Ingestion
of Well Water Contaminated by Phenol*
Symptom
Vomiting
Diarrhea
Headache
Skin rash
Mouth sores
Paresthesia or numbness
Abdominal pain
Dizziness
Dark urine
Burning with urination"1"
Fever
Back pain
Burning mouth
Shortness of breath
Percentage of
Study Group
(N = 39)
15.4
41.0**
23.1
35.9
48.7**
13.2
23.1
21.1
17.9
10.3
15.4
20.5
23.1**
10.3
Individuals
Control Group
(N = 119)
13.9
13.5
16.1
22.6
12.6
8.4
11.8
9.3
3.4
10.0
10.9
11.0
6.8
6.7
*Source: Baker, et al. 1978.
**Significantly greater than controls, P
-------
highest daily amount administered in this test consumed, over a
1-year period, the equivalence of approximately 120 LD50 oral
doses.
Heller and Pursell (1938) fed phenol to rats in their drinking
water over several generations. The results of their experiment
are listed in Table 8.
In an unpublished study by Dow Chemical Company (1976) , rats
were fed by gavage 20 daily doses of 0.1 g phenol/kg body weight.
These rats showed slight liver and kidney effects, while rats which
received 20 daily doses of 0.05 or 0.01 g phenol/kg body weight
demonstrated none of those effects. In a subsequent series of
tests, rats received 135 doses of 0.1 or 0.05 g phenol/kg body
weight by gavage over a 6-month period. The growth of the rats
receiving the phenol was comparable to that of the controls. Very
slight liver changes and slight to moderate kidney damage were seen
in the rats which had received 0.1 g phenol/kg. The feeding of
0.05 g phenol/kg resulted only in slight kidney damage.
In a 41-day feeding study, Kociba, et al. (1976) fed 125 mg
phenylsalicylate/kg/day to beagle dogs. Since phenylsalicylate is
metabolized to phenol, this resulted in urinary phenol levels up to
6,144 mg/1. This high level of phenol excretion was not associated
with any discernible ill effects in the dogs. Repeated exposures
to phenol at high concentrations have resulted in chronic liver
damage in man (Merliss, 1972).
C-28
-------
o
I
to
vo
TABLE 8
The Effect of Phenol Solutions Upon Rats*
Phenol
Drinking
Solutions
mg/1
100
500
1,000
3,000
5,000
7,000
8,000
10,000
12,000
Growth
Normal
Normal
Normal
Normal
Normal
Below normal
Fair
Retarded
Retarded
Reproduction
5 generations
5 generations
5 generations
3 generations
3 generations
2 generations
2 generations
Retarded
None
Comments
Splendid condition
Appearance good
Food & water intake satisfactory
General appearance good
General appearance good
Stunted growth in young
Many young died
Young not cared for
Old died in hot weather
*Source: Heller and Pursell, 1938
-------
Synergism and/or Antagonism
No significant evidence could be found to support the occur-
rence of synergistic or antagonistic actions of phenol with other
compounds in mammals.
Challis (1973) reported that phenol could react rapidly with
nitrites in vitro to produce p-nitrosophenol.
Teratogenicity
The work by Heller and Pursell (1938), which has been dis-
cussed previously, demonstrated no significant effects of phenol on
reproduction in rats receiving 100 to 5,000 mg phenol/1 in their
drinking water over 3 to 5 generations. This study, however, was
not designed specifically as a teratogenicity study.
Mutagenicity
Demerec, et al. (1951) reported that phenol produced back-
mutations in E. coli ranging from streptomycin dependence to non-
dependence. Significant back-mutations occurred at 0.1 to 0.2 per-
cent phenol concentrations. However, at these concentrations the
survival of bacteria was only 0.5 to 1.7 percent. Dickey, et al.
(1949) found phenol to be nonmutagenic in Neurospora. Hadorn and
Niggli (1946) found phenol mutagenic in Drosophila after exposing
the gonads of Drosophila to phenol in vitro.
The existing information on the mutagenicity of phenol is
equivocal and needs to be re-examined through the use of better
established methodologies.
Carcinogenicity
Boutwell and Bosch (1959) tested the tumor promoting activity
of phenolic compounds in various strains of mice. Mice that had
C-30
-------
been exposed to a single dose of the initiator 9,10-dimethyl-
1,2-benzanthracene (DMBA) by skin painting were given repeated der-
mal applications of selected phenols. In one experiment in this
series, following initiation with DMBA and promotion by croton oil
through skin painting, mice which had been specially inbred for
sensitivity to develop tumors received a single application of
75 ug DMBA to the shaved skin. This was followed one week later by
twice-weekly dermal applications of 2.5 mg phenol (as a 10 percent
solution in benzene) for 42 consecutive weeks. The mice receiving
this dosage of phenol exhibited severe skin damage, decreased body
weight, and increased mortality. After 13 weeks, 22 out of 23 mice
had developed papillomas, and 73 percent had developed carcinomas.
In a group of mice which were treated with DMBA only, 3 out of 21
survivors exhibited papillomas after 42 weeks. In a group exposed
to twice-weekly skin paintings with 10 percent phenol alone, 5 out
of 14 survivors (36 percent) had papillomas after 52 weeks. The
skin painting with phenol was continued until the 72nd week, at
which time one fibrosarcoma was diagnosed. Other strains of mice
(Holtzman, CAFlf and C3H) also produced papillomas after initiation
with DMBA and subsequent skin painting with 10 percent phenol, but
the incidence was lower. The same schedule of application of
1.25 mg phenol twice-weekly to Rusch's special breed of Sutter mice
resulted in a lower incidence of papillomas and carcinomas. No
carcimomas occurred in the standard breeds of mice when exposed to
phenol without pretreatment with DMBA. Tests with a 20 percent
phenol solution (5 mg/mouse) caused a number of deaths due to
systemic toxicity.
C-31
-------
Salaman and Glendenning (1957) reported that "S" strain albino
mice showed strong promoting activity for tumor formation after in-
itiation with 0.3 mg DMBA followed by repeated skin applications of
20 percent phenol. Twenty percent phenol solutions produced sig-
nificant damage to the skin and were weakly carcinogenic when ap-
plied alone. Phenol in a 5 percent solution had a moderate pro-
moting effect, but was not carcinogenic without previous initia-
tion.
Van Duuren, et al. (1971) found phenol (3 mg/mouse, 3 x/week)
to have only slight promoting activity in ICR/Ha Swiss mice after
initiation with benzo(a)pyrene (BaP). In subsequent experiments,
Van Duuren, et al. (1973) demonstrated that phenol is not cocar-
cinogenic since, when it is repeatedly applied together with BaP,
tumorigenesis is inhibited slightly. This partial inhibitory ef-
fect in cocarcinogenesis experiments was subsequently confirmed by
Van Duuren and Goldschmidt (1976).
In conclusion, phenol appears to have tumor-promoting activity
in many strains of mice when repeatedly applied to the shaved skin
after initiation with known carcinogens. The tumor-promoting ac-
tivity is highest at dose levels of phenol which have some scleros-
ing activity, but also occurs in sensitive strains at phenol con-
centrations which do not produce obvious skin damage. Phenol has
no cocarcinogenic activity when repeatedly applied simultaneously
with BaP to mouse skin, but it reduces the incidence of tumor for-
mation slightly. When applied repeatedly to the skin of a special-
ly bred strain of Sutter mice, phenol exhibits carcinogenic activi-
ty, especially at concentrations which produce repeated skin dam-
:-32
-------
age. Phenol has not been found to be carcinogenic when applied
alone to the skin of standard strains of mice.
While the existing qualitative data derived from skin painting
in one sensitive strain of mice provide suspicion for a weak car-
cinogenic response to phenol, the protocol was found, in agreement
with NIOSH (1976), to be inappropriate and inadequate for the pur-
pose of judging phenol to be a carcinogen in ingested water.
C-33
-------
CRITERION FORMULATION
Existing Guidelines and Standards
In 1974, the Federal standard for phenol in air in the work-
place was 19 mg/m3 or 5 ppm as a time-weighted average (39 FR 125).
This coincided with the recommendation of the American Conference
of Governmental Industrial Hygienists (1977). The NIOSH (1976)
criterion for a recommended standard for occupational exposure to
phenol is 20 mg/m3 in air as a time-weighted average (TWA) for up
to a 10-hour work day and a 40-hour work week, with a ceiling con-
centration of 60 mg/m3 for any 15-minute period.
The U.S. EPA interim drinking water limit for phenol is
0.001 mg/1, which is largely an aesthetic standard based on the ob-
jectionable taste and odor produced by chlorinated phenols; this
limit is identical to the 1962 U.S. PHS Drinking Water Standard.
In response to a phenol spill in southern Wisconsin, the U.S. EPA
proposed on November 26, 1974 a local emergency standard of 0.1 mg
phenol/1 as being temporarily acceptable for human consumption
(Baker, et al. 1978).
Current Levels of Exposure
The National Organic Monitoring Survey (U.S. EPA, 1977) re-
ported finding unspecified concentrations of phenol in 2 out of 110
raw water supplies. The survey found no phenol in any finished wa-
ter supplies. The National Commission on Water Quality (1975) re-
ported that the annual mean phenol concentration in the lower
Mississippi River was 1.5 ug/1 in 1973, with a maximum of 6.7 yg/1.
Endogenously produced phenols in man occur at significantly higher
concentration than this.
C-34
-------
Occupational exposures at a threshold limit value (TLV) of
20 mg/m3 TWA would result in the absorption of 105 mg phenol from
the inspired air, assuming moderate to low activity (7 m air
breathed per eight hours) and an absorption efficiency of 75 per-
cent. During heavier activity (equivalent to 20 m inspired in
eight hours), the absorption would rise to 300 mg phenol for an
8-hour shift. The additional skin absorption would be expected to
substantially increase these quantities.
Special Groups at Risk
In 1976, NIOSH estimated the number of people who may be ex-
posed to phenol to be 10,000. This reflects the number of people
who are employed in the production of phenol, its formulation into
products, or the distribution of concentrated phenol products. In
addition, an uncertain but probably large number of people will
have intermittent contact with phenol as components of medications
or in the workplace as chemists, pharmacists, biomedical personnel,
and other occupations.
Basis and Derivation of Criterion
Heller and Pursell (1938) reported no significant effects in a
multi-generation feeding study in rats at 100, 500, and 1,000 mg
phenol/1 of drinking water for five generations and at 3,000 and
5,000 mg/1 for three generations. Assuming a daily water intake of
30 ml and an average body weight of 300 grams, these rats would
have received doses of 10, 50, 100, 300, and 500 mg/kg/day. The
upper range approaches a single LDcn dose per day. Deichmann and
Oesper (1940) reported no significant effects in rats receiving 21,
30, 49, 56, and 55 mg/day in their drinking water for 12 months.
C-35
-------
However, neither of these studies reported detailed pathological or
biochemical studies, but relied mainly on the weights and general
appearance of the animals for evaluation. In a more recent study
(Dow Chem. Co., 1976), 135 dosings by gavage over six months at
100 mg phenol/kg/dose resulted in some liver and kidney damage. At
50 mg/kg/dose, however, the exposure resulted in only slight kidney
damage. It must be borne in mind that in the first two studies the
phenol was incorporated into the drinking water, so that the daily
dose was taken gradually. In the Dow study, the phenol was admin-
istered in a single slug. A 500-fold uncertainty factor applied to
the 50 mg/kg exposure in the Dow study would provide an estimated
acceptable level of 0.1 mg/kg/day for man.
The 500-fold uncertainty factor was selected for a number of
reasons. In the case of phenol, a great deal of information on
human exposure exists. Long-term animal data are available as well;
however, the detail in these studies is very incomplete. Shorter-
term studies of sufficient detail provide the lowest dose level in
animal studies for which an adverse effect was seen. It was judged
that the existing data did not fully satisfy the requirements for
the use of a 100X uncertainty factor, but were better than the
requirements for a 1,OOOX uncertainty factor [National Academy of
Sciences (NAS), 1977]. Consequently, an intermediate 500X uncer-
tainty factor was selected.
When one examines through use of the Stokinger and Woodward
model (1958) the amount of phenol absorbed through inhalation near
the TLV of 20 mg/m for occupational exposures, one finds that with
a breathing rate of 10 m3/8-hour day and 75 percent absorption, a
C-36
-------
70 kg man would absorb approximately 2.14 mg/kg body weight/working
day, assuming no skin absorption. The use of the Stokinger-Wood-
ward model may be applicable to estimate acceptable intake from
water.
It has been established that phenol is absorbed rapidly by all
routes and is subsequently rapidly distributed. If a 10-fold safe-
ty factor is applied to the projected doses absorbed from inhala-
tion at the TLV (which already incorporates some safety factors) ,
then the projected acceptable level would be 0.2 mg/kg/day. The
estimate from animal data is 0.1 mg/kg/day. On the basis of chron-
ic toxicity data in animals and man, an estimated acceptable daily
intake for phenol in man should be 0.1 mg/kg/day or 7.0 mg/man, as-
suming a 70 kg body weight. Therefore, assuming 100 percent gas-
trointestinal absorption of phenol, the consumption of 2 liters of
water daily and 6.5 g of contaminated fish having a bioconcentra-
tion factor of 1.4 would result in a maximum permissible concen-
tration of 3.5 mg/1 for the ingested water.
The equation for calculating the criterion for the phenol con-
tent of water given an Acceptable Daily Intake (ADI) is
2X + (0.0065) (BCF) (X) = ADI
where
2 = amount of drinking water, I/day
X = phenol concentration in water, mg/1
0.0065 = amount of fish consumed, kg/day
BCF = bioconcentration factor, mg phenol/kg fish
per mg phenol/1 water
ADI = limit on daily exposure for a 70 kg person
2X + (0.0065) (1.4)X = 7.0 mg/day
X = 3.5 mg/1
C-37
-------
This water duality criterion is in the ranae of reported taste
and odor threshold values for phenol listed in Table 2. It must be
noted that this value has been derived for unchlorinated phenol.
It is recoqnized that when ambient water containinq this con-
centration of phenol is chlorinated, various chlorinated phenols
mav be produced in sufficient quantities to produce obiectional
taste and odors (see Introduction). Therefore, while the criterion
for ambient water is 3.5 mq phenol/1, the possible consequences of
chlorination treatment of such water mav have to be considered for
specific local conditions. In those cases where siqnificant chlo-
rination of ambient water is practiced, reference is made to the
water quality criteria for 2-chlorophenol (U.S. EPA, 1980b) and
2,4-dichlorophenol (U.S. EPA, 1980c).
In summary, based on the use of chronic toxicoloqic test data
for rats and an uncertainty factor of 500, the criterion for phenol
correspondinq to the calculated acceptable daily intake of
0.1 mq/kq is 3.5 mq/1. Drinkinq water contributes >• 99 percent of
the assumed exposure, while eatinq contaminated fish products ac-
counts for -=c 1 percent. The criterion level could alternatively be
expressed as 769 mq/1 if exposure is assumed to be from the con-
sumption of fish and shellfish products alone.
Since the odor and taste detection threshold concentrations
for phenol are well below the toxicitv-based criterion level
derived above, the ambient water quality criterion is based on
orqanoleptic data. It should be emphasized that this criterion is
based on aesthetic quality rather than health effects. However, to
the extent that this criterion is derived from the chronic toxicity
C-38
-------
study of Dow Chemical Co. (1976), it is also likely to be protec-
tive of human health.
The data of Hoak (1957); Burttschell, et al. (1959); and Dietz
and Traud (1978) all indicate that low mg concentrations of phenols
in water are capable of producing a discernable odor. Burttschell,
et al. (1959) and Dietz and Traud (1978) further observed a dis-
tinct flavor alteration of water at low and sub-mg levels, respec-
tively, of this chemical. Although 9 of 21 tasters in the Camp-
bell, et al. (1958) study detected the presence of phenols in water
at 14 mg/1 (the lowest tested concentration reported), a taste
threshold of 60 mg/1 was determined based on the methodology of the
experiment. The data from these studies, in particular the Burtt-
schell, et al. (1959) and Dietz and Traud (1978) experiments, are
considered to be reasonably mutually supportive [i.e., Hoak (1957),
10 mg/1 for odor; Burttschell, et al. (1959), >.1.0 mg/1 for odor
and taste; and Dietz and Traud (1978), 4 mg/1 for odor and 0.3 mg/1
for taste].
Therefore, based on the prevention of undesirable organoleptic
qualities, the criterion level for phenol in water is 0.3 mg/1.
This level should be low enough to prevent objectionable organo-
leptic characteristics for most people and still below animal 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 may be more confi-
dently postulated.
C-39
-------
REFERENCES
American Conference of Governmental Industrial Hygienists. 1977.
Threshold Limit Values for Chemical Substances and Physical Agents
in Workroom Environment with Intended Changes for 1977. Cincin-
nati, Ohio.
American Pharmaceutical Association. 1977. Handbook of Nonpre-
scription Drugs. 5th ed.
American Public Health Association. 1971. Standard Methods for
the Examination of Water and Wastewater. 13th ed. Washington,
D.C.
Anonymous. 1975. Chemical and Engineering News. July 28.
Baker, E.L., et al. 1978. Phenol poisoning due to contaminated
drinking water. Arch. Environ. Health. 33: 89.
Bennett, I.L., et al. 1950. Severe acidosis due to phenol poison-
ing - report of two cases. Ann. Intern. Med. 32: 324.
Boutwell, R.K. and D.K. Bosch. 1959. The tumor-promoting action
of phenol and related compounds. Cancer Res. 19: 413.
Burttschell, R.H., et al. 1959. Chlorine derivatives of phenol
causing taste and odor. Jour. Am. Water Works Assoc. 51: 205.
C-40
-------
Campbell, C.L., et al. 1958. Effect of certain chemicals in water
on the flavor of brewed coffee. Food Res. 23: 575.
Capel, I.D., et al. 1972. Species variations in the metabolism of
phenol. Biochem. Jour. 127: 25.
Challis, B.C. 1973. Rapid nitrosation of phenols and its implica-
tions for health hazards from dietary nitrites. Nature. 244: 466.
Chemical Profiles. 1972. Phenol. Schnell Publishing Co., New
York.
Clarke, T.W. and E.D. Brown. 1906. The value of alcohol in carbol-
ic acid poisoning. A clinical experimental study. Jour. Am. Med.
Assoc. 46: 782.
Conning, D.M. and M.J. Hayes. 1970. The dermal toxicity of
phenol - an investigation of the most effective first aid measures.
Br. Jour. Ind. Med. 27: 155.
Deichmann, W. 1942. In; F.A. Patty (ed.), Industrial Hygiene and
Toxicology. 1st ed. 2: 1026.
Deichmann, W.B. 1944. Phenol studies. V. The distribution, de-
toxification, and excretion of phenol in the mammalian body. Arch.
Biochem. 3: 345.
C-41
-------
Deichmann, W.B. and M.L. Keplinger. 1963. Phenols and phenolic
compounds. In; F.A. Patty (ed.), Industrial Hygiene and Toxi-
cology. Interscience Publishers, New York. p. 1363.
Deichmann, W. and P. Oesper. 1940. Ingestion of phenol-effects on
the albino rat. Ind. Med. 9: 296.
Deichmann, W.B. and S. Witherup. 1944. Phenol studies. VI. The
acute and comparative toxicity of phenol and o-, m-, and p-cresols
for experimental animals. Jour. Pharmacol. Exp. Ther. 80: 233.
Delfino, J.J. and D.J. Dube. 1976. Persistent contamination of
ground water by phenol. Jour. Environ. Sci. Health. All: 345.
Demerec, M., et al. 1951. A survey of chemicals for mutagenic ac-
tion on E. coli. Am. Natur. 85: 119.
Dickey, F.H., et al. 1949. The role of organic peroxides in the
induction of mutations. Proc. Natl. Acad. Sci. 35: 581.
Dietz, F. and J. Traud. 1978. Geruchs-und Geschmacks -
Schwellen - Koncentrationen von Phenolkoerpern. Gas-Wasserfach.
Wasser- Abwasser. 119: 318.
Dirmikis, S.M. and A. Darbre. 1974. Gas-liquid chromatography of
simple phenols for urinalysis. Jour. Chromatogr. 94: 169.
C-42
-------
Docter, H.J. and R.L. Zielhuis. 1967. Phenol excretion as a mea-
sure of benzene exposure. Ann. Occup. Hyg. 10: 317.
Dow Chemical Co. 1976. References and literature review pertain-
ing to toxicological properties of phenol. Toxicol. Res. Lab.
(Unpubl. Manuscript)
Duplay, S. and M. Cazin. 1891. On the effect of phenol on animals.
Compt. Rend. Acad. Sci. 112: 627.
Ettinger, M.B., et al. 1951. Sensitive 4-aminoantipyrine method
for phenolic compounds. Anal. Chem. 23: 1783.
Farquharson, M.E., et al. 1958. The biological action of chloro-
phenols. Br. Jour. Pharmacol. 13: 20.
Fishbeck, W.A., et al. 1975. Elevated urinary phenol levels not
related to benzene exposure. Am. Ind. Hyg. Jour. 36: 820.
Folin, 0. and W. Denis. 1915. The excretion of free and conjugated
phenols and phenol derivatives. Jour. Biol. Chem. 22: 309.
Geill, C. 1888. Clinical studies on acute phenol poisoning.
Prag. Med. Wochenschr. 13: 411.
Hadorn, E. and H. Niggli. 1946. Mutations in Drosophila after
chemical treatment of gonads in vitro. Nature. 157: 162.
C-43
-------
Hansch, C. and A.J. Leo. 1979. Substituent Constants for Correla-
tion Analysis in Chemistry and Biology. Wiley-Interscience, New
York.
Harborne, J.B. 1964. Biochemistry of Phenolic Compounds. Aca-
demic Press, New York.
Heller, V.G. and L. Pursell. 1938. Phenol-contaminated waters and
their physiological action. Jour. Pharmacol. Exp. Ther. 63: 99.
Hoak, R.D. 1957. The causes of tastes and odors in drinking water.
Proc. llth Ind. Waste Conf. Purdue Univ. Eng. Bull. 41: 229.
Huff, B.B. 1978. Physicians' Desk Reference. 32nd ed. Medical
Economics Co., Oradell, New Jersey.
Ikeda, M. and H. Ohtsuji. 1969. Hippuric acid, phenol, and tri-
chloroacetic acid levels in the urine of Japanese subjects with no
known exposure to organic solvents. Br. Jour. Ind. Med. 26: 162.
International Joint Commission. 1978. Great Lakes Water Quality
Board. Appendix E: 113.
Kobayashi, K. and H. Akitake. 1975. Metabolism of chlorophenols
in fish. IV. Absorption and excretion of phenol by goldfish. Nip-
pon Suisan Gakkaishi. 41: 1271.
C-44
-------
Kobayashi, K., et al. 1976. Studies on the metabolism of chloro-
phenols in fish. VI. Turnover of absorbed phenol in goldfish.
Bull. Jap. Soc. Sci. Fish. 42: 45.
Kociba, R.J., et al. 1976. Elevated urinary phenol levels in bea-
gle dogs treated with salol. Am. Ind. Hyg. Jour. 37: 183.
Kronlein, R.U. 1873. On cases of acute carbolism. Berliner Klin.
Wochenschr. 10: 605.
Lister, J. 1867. On a New Method of Treating Compound Fracture,
Abcess etc., with Observations on the Condition of Suppuration.
In: Medical Classics. 1937. 2: 28.
Lustre, A.O. and P. Issenberg. 1970. Phenolic components of
smoked meat products. Jour. Agric. Food Chem. 18: 1056.
Macht, D.I. 1915. An experimental study of lavage in acute car-
bolic acid poisoning. Johns Hopkins Hosp. Bull. 26: 98.
Merliss, R.R. 1972. Phenol moras. Mus. Jour. Occup. Med. 14: 55.
Miller, J.J., et al. 1976. The toxicity of dimethoxyphenol and
related compounds in the cat. Toxicol. Appl. Pharmacol. 38: 47.
Model, A. 1889. Poisoning with concentrated phenol in a child
suffering from diphtheria. Ther. Monatsheft. 3: 483.
C-45
-------
National Academy of Sciences. 1977. Drinking Water and Health.
Washington, D.C.
National Commission on Water Quality. 1975. Water quality and en-
vironmental assessment and predictions to 1985 for the lower Mis-
sissippi River and Barataria Bay. Vol. 1. Contract WQ5AC062.
National Institute for Occupational Safety and Health. 1976. Cri-
teria for a Recommended Standard...Occupational Exposure to Phenol.
NIOSH 76-196.
Oehme, F.W. and L.E. Davis. 1970. The comparative toxicity and
biotransformation of phenol. Toxicol. Appl. Pharmacol. 17: 283.
Ohtsuji, J. and M. Ikeda. 1972. Quantitative relationship between
atmospheric phenol vapor and phenol in the urine of workers in bake
lite factories. Br. Jour. Ind. Med. 29: 70.
Piotrowski, J.K. 1971. Evaluation of exposure to phenol: Absorp-
tion of phenol vapour in the lungs and through the skin and excre-
tion of phenol in urine. Br. Jour. Ind. Med. 28: 172.
Roberts, M.S., et al. 1977. Permeability of human epidermis to
phenolic compounds. Jour. Pharmcol. Pharmaceut. 29: 677.
C-46
-------
Ruedemann, R. and W.B. Deichmann. 1953. Blood phenol level after
topical application of phenol-containing preparations. Jour. Am.
Med. Assoc. 152: 506.
Salaman, M.H. and O.M. Glendenning. 1957. Tumor promotion in
mouse skin by sclerosing agents. Br. Jour. Cancer. 11: 434.
Smith, L.S. 1976. Evaluation of instrument for the determination
of phenol in water. U.S. Environ. Prot. Agency. EPA 600/4-76-048.
Sollmann, T. 1957. A Manual of Pharmacology and Its Applications
to Therapeutics and Toxicology. 8th ed. W.B. Saunders Co., New
York.
Stajduhar-Caric, Z. 1968. Acute phenol poisoning. Jour. Forensic
Med. 15: 41.
Stephan, C.E. 1980. Memorandum to J. Stara. U.S. EPA. July 3.
Stokinger, H.E. and R.L. Woodward. 1958. Toxicological methods
for establishing drinking water standards. Jour. Am. Water Works
Assoc. 517.
Tauber, S. 1895. Studies on detoxication therapy. II. The effect
of sulfates and sulfites as well as of sulfur compounds in phenol
poisoning. Arch. Exp. Pathol. Pharmakol. 36: 211.
C-47
-------
Tollens, K. 1905. On the effect of cresols and of liquor cresolis
saponatus as compared with phenol. Arch. Exp. Pathol. Pharmakol.
52: 220.
U.S. EPA. 1977. National Organic Monitoring Survey. General re-
view of results and methodology: Phases I-III. Water Supply Res.
Div.
U.S. EPA. 1980a. Seafood consumption data analysis. Stanford
Research Institute International, Menlo Park, California. Final
rep., Task II. Contract No. 68-01-3887.
U.S. EPA. 1980b. Ambient water quality criteria for 2-chloro-
phenol. EPA-440/5-80-034. U.S. Environ. Prot. Agency, Washington,
D.C.
U.S. EPA. 1980c. Ambient water quality criteria for 2,4-dichloro-
phenol. EPA-440/5-80-042. U.S. Environ. Prot. Agency, Washington,
D.C.
U.S. Public Health Service. 1962. Drinking water standards. U.S.
Dept. Health Edu. Welfare. PHS Pub. No. 956.
Van Duuren, B.L. and B.M. Goldschmidt. 1976. Cocarcinogenic and
tumor-promoting agents in tobacco carcinogenesis. Jour. Natl.
Cancer Inst. 56: 1237.
C-48
-------
Van Duuren, B.L., et al. 1971. Cocarcinogenesis studies on mouse
skin and inhibition of tumor production. Jour. Natl. Cancer Inst.
46: 1039.
Van Duuren, B.L., et al. 1973. Cocarcinogenic agents in tobacco
carcinogenesis. Jour. Natl. Cancer Inst. 51: 703.
Van Haaften, A.B. and S.T. Sie. 1965. The measurement of phenol in
urine by gas chromatography as a check on benzene exposure. Am.
Ind. Hyg. Assoc. Jour. 26: 52.
Veith, G.D., et al. 1979. Measuring and estimating the bioconcen-
tration factor of chemicals in fish. Jour. Fish. Res. Board Can.
36: 1040.
Veith, G.D. 1980. Memorandum to C.E. Stephan. U.S. EPA.
April 14.
Veldrye, I.A. 1972. Experimental basis for maximum permissable
concentrations of certain shale phenols in the water of reservoirs.
Mauch. Prakt. Deyatel. Inst. Eksp. Klin. Med. Tallin 1972: 84.
von Oettingen, W.F. 1949. Phenol and its derivatives: The rela-
tion between their chemical constitution and their effect of the
organism. Natl. Inst. Health. Bull. No. 190.
C-49
-------
Willhard, A. 1886. Examination of the urine of a case of phenol
poisoning. Jahresber. Tierchem. 16: 464.
C-50 ft U. S. GOVERNMENT PWNTJNC OFFICE . I960 720-016/4390
------- |