PHENOL
Ambient Water Quality Criteria
Criteria and Standards Division
Office of Water Planning and Standards
U.S. Environmental Protection Agency
Washington, D.C.
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CRITERION DOCUMENT
PHENOL
CRITERIA
Aquatic Life
For phenol the criterion to protect freshwater aquatic life
as derived using the Guidelines is 600 ug/1 as a 24-hour average,
and the concentration should not exceed 3,400 u.g/1 at any time.
For saltwater aquatic life, no criterion for phenol can be
>
derived using the Guidelines, and there are insufficient data to
estimate a criterion using other procedures.
Human Health
For the protection of human health from phenol ingested
through water and through contaminated aquatic organisms the con-
centration in water should not exceed 3.4 mg/1.
For the prevention of adverse effects due to the organoleptic
properties of chlorinated phenols inadvertently formed during
water purification processes, the phenol concentration in water
should not exceed 1.0 ug/1.
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PHENOL
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 impurities are present), hygroscopic, deliquescant,
crystalline solid at 25°C (Manufacturing Chemist Assoc.
1964; Kirk and Othmer, 1963; Weast, 1974). It has the empiri-
cal formula CgHgO, a molecular weight of 94.11, a specific
gravity of 1.071 at 25°C/4°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
to form salts called phenoxides (Weast, 1974; Kirk and Othmer,
A-l
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1963) . Phenoxides exist in highly alkaline aqueous solutions
and many, particularly the sodium and potassium salts, are
readily soluble in water.
Natural phenol is produced by the distillation of coal
tar, although this source constitutes only one to two 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
i
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 catalyst (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 synthetic 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).
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Phenol or phenolic wastes also are produced during
the coking of coal, distillation of wood, operation of gas
works and oil refineries, livestock dips, human and animal
wastes, and microbiological decomposition of organic matter
(Bulick, 1950; Mischonsniky, 1934).
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 hydroxylated to ortho- and paradi-
hydroxybenzenes and readily oxidized to the corresponding
benzoquinones. These may in turn react with numerous compo-
nents of industrial waters or sewage such as mercaptans,
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 reactivity to the phenyl ring, particularly the ortho-
and para positions. 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 soultions
to form 2-chloro-, 4-chloro-, or higher chlorophenols has
been demonstrated under conditions similar to those used
for disinfection of waste water effluents (Aly, 1968; Barnhart
and Campbell, 1972) and represents a potential amplification
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of the organoleptic problems associated with phenol contamina-
tion. Synthesis of 2-chlorophenol within one hour in aqueous
solutions containing as little as 10 mg/1 phenol and 20 mg/1
chlorine has been reported (Barnhart and Campbell, 1972).
Other studies have reported 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 (Jolly, 1973, Jolly, et al. 1975). These observations
are highly significant in view of the ability of the chloro-
phenols to cause tainting of fish flesh at lower concentrations.
The property of 2-chlorophenol and 2,4-dichlorpphenol to
impart an odor to water and a taint to the flesh of aquatic
organisms at concentrations varying from 0.33 jug/1 to 15.0
flg/I and 0.65 jug/1 to 10.0 jng/1, respectively, has been reported
(see 2-chlorophenol and 2,4-dichlorophenol criterion documents).
This represents a possible potentiation in the organoleptic
properties of phenol in water by approximately 30,000-fold.
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 tetrahydroxybiphenyls, quinones
and diphenols. Aqueous phenol solutions irradiated with
sunlight for seven days were reported to degrade to hydrcoqui-
none and pyrocatechol (Perel'shtein and Raplin, 196.8)..
A-4
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Subsequent irradiation of pyrocatechol with sunlight for
Si
seven days yielded pyrogallol. The end products of photode-
composition were reported to be humic acids. Conversely,
similar studies utilizing natural sunlight as the source
of irradiation indicated that phenol concentrations in solu-
tions 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 stearother-
mophilus, to catabolize phenol. In these studies, the bacteria
first converted phenol to catechol and subsequently cleaved
the aromatic ring to form 2-hydroxymuconic semialdehyde.
In view of the fact that phenol represented the primary
carbon source provided to isolated and adapted microorganisms
in these studies, the importance or microbiological degradation
within the environment remains unclear.
Although phenol appears to be less toxic than the chlori-
nated phenols and certain other substituted phenols, its
toxicity to microorganisms, plants, aquatic organisms and
mammals, including man, has been demonstrated. Phenol also
A-5
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has been reported to exhibit carcinogenic activity in mice.
These findings, together with potential pollution from waste
sources and the possible chlorination of phenol present
in drinking water sources, indicate that phenol is potentially
hazardous to aquatic and terrestrial life.
Information concerning the presence and persistence,
and fate of phenol in the environment is incomplete or not
available. A limited number of studies indicate that phenol
does not bioconcentrate appreciably in aquatic organisms.
The widespread use of phenol as an important chemical
intermediate,- the generation of phenolic wastes by industry
and agriculture, and the toxicological and organoleptic
properties indicate its importance in potential point source
and nonpoint source water contamination.
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REFERENCES
Aly, O.M. 1968. Separation of phenols in waters by thin-
layer chromatography. water Res. 2: 287.
American Industrial Hygiene Assoc. 1957. Hygienic guide
series: Phenol. Am. Ind. Hyg. Assoc. Detroit.
Audureau, J., et al. 1976. Photolysis and photooxidation
of phenol in aqueous solutions. Jour. Chem. Phys. 73: 614
Barnhart, E.L., and G.R. Campbell. 1972. The effect of chlori-
nation on selected organic chemicls. U.S. Environ. Prot.
Agency. U.S. Government Printing Office, 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.
Abstr. 31, Palivo 30: 308.
Buswell, J.A. 1975. Metabolism of phenol and cresols by
Bacillus stearothermophilus. Jour. Bact. 17.
j
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-7
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Carlson, R.M., and.R. Caple. 1975. Organo-chemical implication
of water chlorination. p. 73 jn Proc. Conf. Environ. Impact
Water Chlorination.
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.
Jolly, R.L. 1973. Chlorination effects on organic constituents
in effluents from domestic sanitary sewage treatment plants.
Ph. D. dissertation, University of Tennessee, Knoxville.
Jolly, R.L., et al. 1975. Chlorination of cooling water:
a source of environmentally significant chlorine - containing
organic compounds. Proc. 4th Natl. Symp. Radioecology. Corvallis,
Ore.
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. 1974. Chemical safety data
sheet SD-4; Phenol. Washington, D.C.
A-8
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Middaugh, D.P., and W.P. Davis. 1976. Impact of chlorination
processes on marine ecosystems. P. 46. ^n Water quality
research of the U.S. Environ. Prot. Agency. EPA Report No.
600/3-76-079. U.S. Environ. Prot. Agency, Washington, D.C.
Mischonsniky, S. 1934. A study of the pollution of fish
containing 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 intact cells and cell-free preparations of Trichosporon
cutaneum. Eur. Jour. Biochem. 13: 37.
Patty, F.A. 1963. ed. Industrial hygiene and toxicology.
John Wiley and Sons, Inc., New York.
6
Perel'shtein, E.I., and V.T. Kaplin. 1968. Mechanism of
the self purification of inland surface waters by the removal
of phenol compounds. II. Effect of natural uv rays on aqueous
solutions of phenol compounds. Gidrokhim. Mater. In Chem.
Abstr. Vol. 84, 48: 139.
Sax, N.I. 1975. Dangerous properties of industrial materials.
4th ed. Van Nostrand Reinhold Co., New York.
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Spector, W.S. 1956. Handbook of toxicology. W.B. Saunders
Co., Philadelphia.
Stecher, P.G. 1969. ed. The Merck Index. Merck and Co.,
Rahway, N.J.
Stom, D.J. 1975. Use of thin-layer and paper chromatography
for detection of ortho- and para- quinones formed in the
course of phenol oxidation. Acta Hydrochim. Hydrobiol. 3: 39
Tomkiewicz, M., et al. 1971. Electron paramagnetic resonance
spectra of semiquinone intermediates observed during the
photooxidation of phenol in water. Jour. Am. Chem. Soc.
93: 7102.
Weast, R.C. 1974. ed. 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. Hydrobiologica 24: 540.
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IQUATIC LIFE TOXICOLOGY*
FRESHWATER ORGANISMS
Introduction
Phenol is predominantly used as an intermediate in a wide
variety of chemical processes. These processes produce epoxy and
phenolic resins, pharamaceuticals, germicides, fungicides, slimi-
cides, herbicides, dyes, and a variety of industrially important
acids. The phenol molecule easily substitutes 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
bacteria and fungi that may cause slime growths and depress
dissolved oxygen in the receiving waters, thus lowering water
quality.
Although an abundance of data on the acute toxicity of phenol
tja fish and invertebrate species and plants is available, the
chronic toxicity data are limited to one test on Daphnia magna.
Toxicity testing on the same species by different researchers in
different waters produced LC50 values which varied widely. This
*The reader is referred to the Guidelines for Deriving Water
Quality Criteria for the Protection of Aquatic Life [43 FR 21506
(May 18, 1978) and 43 FR 29028 (July 5, 1978)] in order to better
understand the following discussion and recommendation. The fol-
lowing tables contain the appropriate data that were found in the
literature, and at the bottom of each table are the calculations
for deriving various measures of toxicity as described in the
Guidelines.
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indicates that water quality parameters such as pH, hardness, tem-
perature, and others may alter the toxicity of the compound.
Acute Toxicity
Acute toxicity data for 13 species of fish are included in
Table 1. Rainbow trout, the most sensitive fish species tested,
had the lowest adjusted LC50 concentration of 2,624 ug/1 (Cairns,
et al. 1978). The least sensitive species was the goldfish with
adjusted LC50 concentrations as high as 93,720 ug/1 (Cairns, et
al. 1978).
There is a wide range of interspecific variability in addi-
tion to the wide range of intraspecific sensitivity previously
mentioned. Adjusted LC50 concentrations for rainbow trout varied
from 2,624 ug/1 ((SaTrns, et al. 1978) to 11,600 ug/1 (Fogels and
Sprague, 1977). The fathead minnow, a commonly used test species,
had adjusted LC50 concentrations that varied from 17,494 ug/1
(Pickering and Henderson, 1966; Mattson, et al. 1976) to 67,500
ug/1 (U.S. EPA, 1978b). The bluegill, another commonly used test
species, had adjusted LC50 concentrations from 6,287 ug/1 (Cairns
and Scheier, 1959) to 28,116 ug/1 (Cairns, et al. 1978).
Several studies showed the effects of temperature on phenol
toxicity. Brown, et al. (1967a, b) demonstrated an inverse rela-
tionship between survival time and temperature when rainbow trout
were exposed to phenol at 6.3°, 11.8°, and 18.1°C. The adjusted
LC50 concentrations at these respective temperatures are 3,106,
4,601, and 5,636 ug/1. The same relationship was shown by Cairns,
et al. (1978) with the golden shiner; however, these same inves-
tigators found rainbow trout to be more sensitive at 5°C with an
adjusted LC50 concentration of 2,624 ug/1 than at 12V arid 18°C
B-2
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with adjusted LC50 concentrations of 5,155 ug/1 and 5,295 ug/1/
respectively. Ruesink and Smith (1975) conducted tests on fathead
minnows at 15° and 25°C and found 96-hour LC50 values of 36,000
U9/1 and 24,000 ug/1.
Because of the wide variation in species sensitivity, it
appears that division by the appropriate sensitivity factor \is
necessary to derive a Final Fish Acute Value for phenol to protect
the more sensitive salmonid species. Although the adjusted LC50
values for rainbow trout from three tests conducted under static
or renewal conditions (McLeay, 1976; Brown, et al. 1967a, b;
Cairns, et al. 1978) were slightly lower than the Final Fish Acute
Value of 4,000 ug/lf all adjusted LC50 values for rainbow trout in
flow-through measured tests (Mitrovic, et al. 1968; U.S. EPA,
1978b; Fogels and Sprague, 1977) are above the Final Fish Acute
Value. Since the Final Fish Acute Value is protective of the most
sensitive fish species under flow-through conditions, this sug-
gests a reasonable fit of the data to the procedures in the
Guidelines.
Toxicity data for the 13 invertebrate species, including
rotifers, annelids, snails, clams, cladocerans, conchostracans,
and isopods, are listed in Table 2. Tests conducted by Alekseyev
'i
and Antipin (1976) are an indication of the relative sensitivity
of several invertebrate species since these tests were conducted
using the same water and similar test methods for all species.
They found adjusted LC50 concentrations ranging from 5,463 ug/1
for the adult isopod, Asellus aquaticus, to 284,084 ug/1 for the
clam, Sphaerium corneum. Data in Table 2 indicate that snails
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and clams are among the least sensitive invertebrate species to
phenol while the cladocerans are among the more sensitive.
Cairns, et al. (1978) determined adjusted LC50 concentrations
that are up to 19 times higher than the LC50 concentrations re-
ported by the other five researchers who tested cladocerans.
Cairns, et al. (1978) tested phenol at different temperatures with
the same water quality parameters and found fairly uniform LC50
concentrations that ranged from 96,800 ug/1 to 110,000 ug/1 for
Daphnia magna and 86,900 ug/1 to 102,300 ug/1 for Daphnia pulex.
The mean of adjusted LC50 concentrations for all other cladoceran
tests was 25,071 ug/1 with a range of 5,929 ug/1 to 84,700 ug/1
for Daphnia magna {Dowden and Bennett, 1965). Dowden and Bennett
(1965) found young Daphnia magna to be about three times more
sensitive than adults.
The range of species sensitivity displayed in Table 2 (the
highest adjusted LC50 divided by the lowest) is 52 times. This
indicates that division by a sensitivity factor is advisable to
obtain a Final Invertebrate Acute Value that will protect the more
sensitive invertebrate species. The Final Invertebrate Acute
Value of 3,400 ug/1 is only 1.7 times lower than the lowest
adjusted acute value, which indicates a reasonable fit of the data
to the procedures in the Guidelines. Since 3,200 ug/1 is lower
than the Final Fish Acute Value, it becomes the Final Acute Value
for freshwater aquatic life.
Chronic Toxicity
No data dealing with chronic effects of phenol on freshwater
fish are available, but one chronic test with an invertebrate
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species was found (Table 3). In a life cycle chronic test (U.S.
EPA, 1978a) a chronic value concentration of 3,074 ug/1 was deter-
mined for the cladoceran Daphnia magna. The adjusted 48-hour EC50
concentration for daphnids from the same study was 9,995 ug/1.
The range of sensitivity for invertebrate species cannot be deter-
mined from chronic data, but may be inferred from acute toxicity
data (Table 2). With the possible exception of data determined by
Cairns, et al. (1978), it appears that Daphnia magna is one of the
more sensitive invertebrate species to phenol. However, because
of the large variation in sensitivity of invertebrate species to
various toxicants and because the chronic value for phenol is
close to the adjusted LC50 concentrations for several invertebrate
species, reduction of the chronic value by the sensitivity factor
would yield a Final Invertebrate Chronic Value that would be more
likely to protect sensitive invertebrate species for extended ex-
posure periods. Thus, the Final Invertebrate Chronic Value of 600
ug/1 becomes the Final Chronic Value for phenol since that value
is lower than the lowest values derived from chronic data for
plants (Table 4) and from other data (Table 5).
Plant Effects
/
Plants are relatively insensitive to phenol exposure, and all
reported plant effects are much higher than the Final Chronic
Value of 600 ug/1. Reynolds, et al. (1975) reported up to 66 per-
cent cell number reduction with the alga, Selenastrum capri-
cornutum (Table 4), after two days at 24°C at 20,000 ug/1. There
are two values given for chlorosis (the destruction of chloro-
phyll). Huang and Gloyna (1968) reported the complete destruction
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of chlorophyll in Chlorella pyrenaidosa in two days at 1,500,000
ug/1, and Blackman, et al. (1955) reported an EC50 concentration
of 1,504,000 ug/1 based on chlorosis in the duckweed Lemna minor.
Simon and Blackman, (1953) found a 50 percent reduction in growth
at 479,400 ug/1/ which was approximately three times lower than
the concentration causing chlorosis in the same species. The
diatom, Nitzschia linearis, had a 50 percent growth reduction in
120 hours at 258,000 ug/1 (Patrick, et al. 1968).
The Final Plant Value is 20,000 ug/1/ based on data of
Reynolds, et al. (1975).
Residues
Table 5 contains bioconcentration data on phenol for gold-
fish. However, since no maximum permissible tissue concentra-
tion is available for phenol, no Residue Limited Toxicant Concen-
tration can be calculated. The bioconcentration factors calcu-
lated for phenol (Kobayashi, et al. 1976; Kbbayashi 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.
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CRITERION FORMULATION
Freshwater - Aquatic Life
Summary of Available Data
The concentrations below have been rounded to two significant
figures.
Final Fish Acute Value = 4,000 ug/1
Final Invertebrate Acute Value = 3,400 ug/1
Final Acute Value = 3,400 ug/1
Final Fish Chronic Value = not available
Final Invertebrate Chronic Value = 600 ug/1
o
Final Plant Value = 20,000 ug/1
Residue Limited Toxicant Concentration = not available
Final Chronic Value = 600 u9/l
0.44 x Final Acute Value = 1,500 ug/1
The maximum concentration of phenol is the Final Acute Value
of 3,400 ug/1 and the 24-hour average concentration is the Final
Chronic Value of 600 ug/1- No important adverse effects on
freshwater aquatic organisms have been reported to be caused by
concentrations lower than the 24J-hour average concentration.
CRITERION: For phenol the criterion to protect freshwater
aquatic life as derived using the Guidelines is 600 ug/1 as a
24-hour average, and the concentration should not exceed 3,400 ug/1
at any time.
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Table 1. Freshwater fish acute values for phenol
Adjusted
09
oo
Organism
Bioaesay Test
Methud* Cone .** (hrs)
Rainbow trout
(juvenile) ,
S a lino gairdneri
Rainbow trout
(juvenile) ,
Sal mo g.'iirdnfcri
Rainbow trout
(juvenile) ,
Sal mo gairdneri
Rainbow trouc
(juvenile) ,
Salmo gairdneri
Rainbow trout
(juveni le) ,
Salmo gairdneri
Rainbow trout
(juvenile) ,
Salmi) gairdneri
Rainbow trout
(yearling) ,
Salmo gairdnuri
Rainbow trout ,
Salmo gairdneri
Rainbow trout,
Snlmo gairdneri
Rainbow trout,
Sulmo gairdneri
Rainbow trout,
Salmo gjiirdneri
Brook trout (juvenile) ,
Salvclinus fontinalis
fioldfish,
R
R
R
R
FT
FT
R
S
S
S
FT
S
S
u
M
M
M
M
M
M
M
M
M
M
U
M
Lme
UTB)
96
48
48
48
48
96
48
LC50
(ug/11
5,020
5,400
8,000
9.800
7,500
8,900
9,400
LC50
(uq/lj
2 , 744
3.106
4,601
5.636
6,075
8,900
5,406
Keference
McLeay, 1<
Brown, et
Brown, et
Brown, et
Mltrovlc,
U.S. EPA,
Brown & Di
24
5.600 2.624 Cairns, et al. 1978
Carassius auratus
24 11,000 5.155 Cairns, et al. 1978
24 11,300 5,295 Cairns, et al. 1978
96 11,600 11.600 Fogels & Sprague. 1977
24 11,700 4,222 Miller & Ogilvie, 1975
24 200,000 93,720 Cairns, et al. 1978
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Table 1. (Continued)
Bioassay
Organism Method*'
Goldfish.
Carassius auratus
Golden shiner,
Notemigonius crysoleueus
Golden shiner.
Notemigontus crysoleueus
Fathead minnow (adult) ,
Pimephales promelas
Fathead minnow (adult) ,
Pimephales promelas
Fathead minnow.
1 Pimephales promelas
vo
Fathead minnow,
Pimephales promelas
Fathead minnow (adult) .
Pimephales promelas
Fathead minnow (adult) ,
Pimephales promelas
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimephales promelas
Walking catfish,
Clarias batraehus
Channel catfish
(juvenile) ,
Ictaluras punctatus
Flagfish,
Jordanella floridae
Mosquitof ish,
S
S
S
S
FT
S
S
FT
FT
FT
S
R
S
FT
S
Test
Cone,**
U
M
M
U
M
U
U
M
M
M
U
U
U
M
M
Time
ihrs)
96
24
24
24
96
96
96
96
96
96
96
48
96
96
96
LC50
(uq/11
44.490
129,000
35,000
65,340
67,500
34.270
32.000
36,000
24,000
28,780
32.000
31.500
16,700
36.300
26.000
Adjusted
LC50
(uq/U
24,323
60.449
16,401
23,576
67,500
18,735
17.494
36,000
24,000
28,780
17,494
13,949
9,130
36,300
18,460
Heterei.ce
Pickering & Henderson,
1966
Cairns, et al. 1978
Cairns, et al. 1978
Jenkins, 1960
U.S. EPA, 1978b
Pickering & Henderson,
1966
Pickering & Henderson,
1966
Ruesink & Smith, 1975
Ruesink & Smith. 1975
Phipps, et al.
Manuscript
Mattson, et al. 1976
Mukherjee & Bhattacharya.
1974
Clemens & Sneed,
1959
Fogels & Sprague, 1977
Nunogawa, et al . 1970 ,
Gambusia affinis
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Table 1., (Continued)
Organism
Bioassay Test Time
Mettiod* cone.** (hrs)
Ad lusted
LCbO LC50
(uq/i) jug/11 Keterei.ce
M
O
Guppy, S
Poecilia retlculatus
Guppy, S
Poecilia reticulatus
Mollies (adult), S
MolLienesla latipinna
Mollies (adult), S
Molltenesia latipinna
Bluegill, S
Lepomis macrochirus
Bluegill (juvenile), R
Lepomis macrochirus
Bluegill, S
Lepomis macrochirus
Bluegill, S
Lepomis macrochirus
Bluegill, S
Lepomis macrochirus
Bluegill (juvenile), R
Lepomis macrochirus
Bluegill (juvenile), S
Lepomis macrochirus
Bluegill, S
Lepomis macrochirus
Bluegill, S
Lepomis macrochirus
Mozambique mouthbrooder, S
Tilapia moaaambica
M
U
U
U
U
M
U
U
U
U
U
M
U
M
96
96
25
50
96
96
96
96
96
48
48
24
96
96
31.000
22,010 Nunogawa. et al. 1970
39,190 21,425 Pickering & Henderson
1966
63,000 22,732 Dowden & Bennett, 1965
22,000 9,742 Dowden & Bennett, 1965
13,500
22,200
7,380 Patrick, et al. 1968
19,300 13,703 Trama, 1955
13,500 7,380 Cairns & Scheier, 1959
20,000 10,934 Cairns & Scheier, 1959
11,500 6,287 Cairns & Scheier. 1959
9.831 Lammering & Burbank. 1960
19,000 8.414 Turnbull. et al. 1954
60,000 28,116 Caims, et al. 1978
23,880 13.055 Pickering & Henderson,
1966
19,000 13,490 Nunogawa, et al. 1970
* S - static, R renewal, FT » flow-through
** u >» unmeasured, M ° measured
Geometric mean of adjusted values - 15,617 yg/1 "'£<)' ° 4.000 yg/1
Lowout value from a flow-through test with measured concentrations = 6,100 ug/1
15,617
-------
Table 2. Freshwater invertebrate acute values for phenol
Organism
tiioassay Test Time LC50
* Cone. ** (ins) fu'i/1)
Adjusted
LCbO
liui/ll hetetcncfc
00
Rotifer, S U
Philodina acuticornis
Rotifer. S M
Philodina acuticornis
Rotifer. S M
Philodina acuticornis
Rotifer. ^ S M
Philodina acuticornis
Rotifer. S M
Philodina acuticornis
Rotifer. S M
Philodina acuttcornis
Annelid. S M
Aeolosoma headleyi
Annelid, S M
Aeolosoma headleyi
Annelid. S M
Aeolosoma headleyi
Annelid. S M
Aeolosoma headleyi
Annelid, S M
Aeolosoma headleyi
Snail, R U
Limnaea stagnalis
Snaii, S M
Nitrocris sp.
Snail, S M
Nicrocris sp.
Snail, S M
Nicrocris sp.
96 248.000 210.056 Buikema. et al. 1974
48 300.000 141.900 Cairns, et al. 1978
48 282.000 133.386 Cairns, et al. 1978
48 245.000 115.885 Caims. et al. 1978
48 205.000 96,965 Cairns, et al. 1978
48 292,000 138.116 Cairns, et al. 1978
48 360.000 170.280 Cairns, et al. 1978
48 351,000 166,023 Cairns, et al. 1978
48 381.000 180.213 Cairns, et al. 1978
48 356.000 168,388 Cairns, et al. 1978
48 341.000 161.293 Cairns, et al. 1978
48 350.000 127.474 Alekseyev & Antipin. 1976
48 389.000 183.997 Cairns, et al. 1978
48 351,000 166,023 Cairns, et al. 1978
48 353.000 166.969 Cairns, et al. 1978
-------
Table 2. (Continued)
Organlarn
Snail,
Nitrocris sp.
Snail,
Nitrocris sp.
Snail (adult),
Physa fontinalis
Snail (juvenile),
Physa fontinalis
Snail,
Physa heterostropha
Clam,
CO Sphaerium comeum
1
{^ Cladoceran,
Daphnia longispina
Cladoceran,
Daphnia magna
Cladoceran,
Daphnia magna
Cladoceran,
Daphnta magna
Cladoceran (young) ,
Daphnia magna
Cladoceran (adult),
Daphnia magna
Cladoceran,
Daphnia magna
Cladoceran,
Daphnia magna
Cladoceran,
Daphnia magna
Bioassay Test
Method * Cone.**
S
S
R
R
S
R
R
S
S
S
S
S
S
S
S
M
M
U
U
U
U
U
' U
U
U
U
U
M
M
M
Time
Ihrs)
48
48
48
48
96
48
48
48
48
48
50
50
48
48
48
LC50
(uq/11
360,000
391,000
320,000
260,000
94,000
780,000
14,000
9,600
11,800
100.000
7.000
21,000
100,000
92.000
91,000
Adjusted
LC50
(uq/1)
170.280
184,943
116,547
94,695
79,618
284,084
11,858
8.131
9,995
84,700
5.929
17,787
110.000
101,200
100,100
Reference
Caims, et al. 1978
Caims, et al. 1978
Alekseyev & Antipin, 1976
Alekseyev & Antipin, 1976
Patrick, et al. 1968
Alekseyev & Antipin, 1976
Alekseyev & Antipin, 1976
Kopperman, et al. 1974
U.;S-r-EPA, 1978a
Dowden & Bennett, 1965
Dowden & Bennett, 1965
Dowden & Bennett, 1965
Cairns, et al. 1978
Cairns, et al. 1978
Cairns, et al. 1978
-------
Table 2. (Continued)
Adjusted
Organism
Cladoceran,
Daphnia magna
Cladoceran,
Daphnia magna
Cladoceran,
Daphnia pulex
Cladoceran,
Daphnia pulex .
Cladoceran,
Daphnia pulex
Cladoceran,
03 Daphnia pulex
J^ Cladoceran,
Daphnia pulex
Cladoceran,
Daphnia pulex
Cladoceran,
Daphnia pulex
Cladoceran,
Polyphemus pediculus
Copepod,
Cyclops vernal is A
Copepod,
Mesocyclops leukarti
Conchostracan,
Lynceus brachyurus
Isopod (adult) ,
Bioassay Test
Method* Cone . **
S M
S
S
S
S
S
S
S
R
R
S
S
R
R
M
U
M
M
M
M
M
U
U
U
U
U
U
Time
48
48
48
48
48
48
48
48
48
48
96
96
48
48
LCbO
(uq/1)
88,000
91
28
93
87
85
81
79
18
57
122
108
78
15
,200
,000
,000
,800
,000
,000
,000
,000
,000
,000
,000
,000
,000
LC50
(uq/1)
96.
100,
23,
102,
96.
93,
89,
86,
15,
48,
103,
91.
28,
5,
800
320
716
300
580
500
100
900
246
279
334
476
408
463
Reference
Cairns, et
Cairns, et
Lee, 1976
Cairns, et
Cairns, et
Cairns, et
Cairns, et
Cairns, et
Alekseyev
Alekseyev
Anderson,
Anderson,
Alekseyev
Alekseyev
al. 1978
al. 1978
al. 1978
al. 1978
al. 1978
al. 1978
al. 1978
& Antipin,
& Antipin,
et al. 1948
et al. 1948
& Antipin,
& Antipin,
1976
1976
1976
1976
Asellus aquaticus
-------
I-1
*»
Organism
Table 2. (Continued)
Bioaesay Test Time
Method* Conc.**> (hra)
LC50
AdjUsted
LCSU
tug/1) fteterence
Isopod (juvenile),
Asellus aquatlciis
U
78,000 28,408 Alekseyev & Antipin. 1976
* S static, R renewal
** U unmeasured, M * measured
Geometric mean of adjuster! values - 70,549 ng/1 ?f " 3,400 vgll
-------
to
I
»-*
en
Table 3. Freshwater Invertebrate chronic values for phenol (U.S. EPA, 1978a)
Chronic
Limits Value
Organism Testr'-" (ug/i) (uq/l|
Cladoceran. LC 1,500-6.300 3,074
Daphnia magna
* LC = life cycle or partial life cycle
Geometric mean of chronic values = 3,074 iig/1 ~5T~ " *>00 wg/1
Lowest chronic value * 3,074 ug/1
-------
Table 4, Freshwater plant effects for phenol
OrganJam
Etfect
Concentration
(uq/J.1
00
Alga,
Chlorella pyrenaidosa
Alga,
Chlorella vulgarls
Duckweed,
Lemna minor
Duckweed,
Lemna minor
Diatom,
Nitzschia linearis
Alga,
Selenastrum
caprlcornutum
Alga.
Selenastrum
capricornu.tum
Alga,
Selenastrum
caprlcornutum
Alga,
Selenastrum
capricornutum
Alga,
Selena strum
caprlcornutum
Alga,
Selenastrum
caprlcornutum
Complete 1
destruction of
chlorophyll in
2 days
20% inhibition
of growth in
80 hrs
Chlorosis 1
(LC50)
50% reduction
in growth
50% reduction
in cell
production in
120 nrs
12% growth
inhibition
at 20° C
27% growth
inhibition
at 24° C
32% growth
inhibition
at 28° C' '
>50% reduction
of 1-day steady
s'tate cell
concentration
58% reduction
in cell numbers
in 1.92 days
at 20° C
66% reduction in
cell numbers in
2.0 days at 24° C
,500,000
470.000
,504,000
479,400
258.000
20.000
20,000
20,000
40,000
20,000
20.000
Reference
Huang & Gloyna, 1968
Dedonder & Van Sumere, 1971
Blacknian, et al. 1955
Simon & Blackman, 1953
Patrick, et al. 1968
Reynolds, et al. 1973
Reynolds, et al. 1973
Reynolds, et al. 1973
Reynolds, et al. 1975
Reynolds, et al. 1975
Reynolds, et al. 1975
-------
Table 4. (Continued)
Concentration
Organism Effect (ug/i> Referfcnce
Alga, 60% reduction 20,000 Reynolds, et al. 1975
Selenastrum in cell numbers
capricornutum in 2.26 days
~~ at 28° C
Lowest plant value « 20,000 ng/1
01
-------
Table 5. Freshwater residues for phenol
Organism
Goldfish,
Carassius auratus
Goldfish,
Carassius auratus
Goldfish,
Carassius auratus
Time
Bioconcentration factoz (days) neterence
2.0 1 Kobayashi, et al.
1976
2.0 5 Kobayashi & Akitake,
1975
1.2-2.3 5 Kobayashi & Akitake,
1975
03
00
-------
Table 6. Other freshwater data for phenol
Test
Otq.iiiism !J!i£ilEiyU t.'t 1 cct.
Paramecium, 19-25 hrs >50% decrease in
Chilomonas paramecium growth from control
Paramecium 44-48 hrs >50% decrease in
Chilomonas paramecium growth from control
Paramecium, 98-163 hrs >50% decrease in
Chilomonas paramecium growth from control
Cladoceran (young) ,
Daphnia magna
Cladoceran (adult),
Daphnia^ magna
Cladoceran,
Daphnia magna
ro
^, Coho salmon (fingerling) ,
us Oncorhynchus kisutch
Rainbow trout,
Salmo gairdneri
Rainbow trout (juvenile) ,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Brook trout (juvenile) ,
Salvelinus fontinalis
Goldfish,
Carassius auratus
Goldfish,
96 hrs Immobilization
(EC50)
96 hrs Immobilization
(EC50)
16 hrs Immobilization
72 hrs LC66.7
114 min 507, mortality
2 hrs Gill damage
48 hrs Lowest concentration
which killed 50% or
more of the test fish
24 hrs Temperature selection
shifted significantly
downward
8 hrs LC62
8 hrs LC67
Kcsult
Jii£l/il
200,000
200,000
200,000
5,000
14,000
94,000
5,630
12,200
6,500
10,000
7,500
33,300
41,600
h«r.- 1. <.»:»=
Cairns, et al. 1978
Cairns, et al. 1978
Cairns, et al. 1978
Anderson, et al. 1948
Anderson.,. ,et al. 1948
Anderson, 1944
Holland, et al. 1960
Herbert, 1962
Mitrovic, et al. 1968
Shumway & Palensky, 1973
Miller & Ogilvie, 1975
Gersdorff, 1939
Gersdorff & Smith, 1940
Carassius auratus
-------
Table 6. (Continued)
Organism
Test
Duration Ettect
Result
(uu/il Ret ereii
10
O
Goldfish,
Carassius auratus
20-30 hrs 50% mortality
Fathead minnow (adult), 216 hrs
Pimephalea promelas
Fathead minnow
(adult),
Pimephales promelas
Ruppy (adult),
PoGcilia reticulatus
Bluegill,
Lepomis macrbchirus
122-127 hrs
30 days
25 hrs
Mozambique mouthbrooder, 1 mo
Tilapia mossambtca
Median lethal
threshold
concentration
Median lethal
threshold
concentration
increase in
heuro-secratory
hormone
50% mortality
between
Manifest
hemosiderosis
in the spleen
40,000- Kobayashi & Akitake, 1975
100,000
27,000 Ruesink & Smith, 1975
22,000 Ruesink & Smith, 1975
3,120 Matei & Flerov, 1973
10,000- Dowden & Bennett, 1965
15,000
2,000 Murachi, et al. 1974
Lowest value - 2,000 ug/1
-------
SALTWATER ORGANISMS
Acute Toxicity
The data base on the effects of phenol on saltwater organisms
is limited to acute toxicity tests on three fish and two mollusc
species. The LC50 was 5,200 ug/1 (48-hour) for rainbow trout,
Salmo gairdneri, 6,014 ug/1 (96-hour) for mountain bass, Kuhlia
sandvicensis, and 510 ug/1 (12-hour) for Stolephorus purpuratus
(Tables 7 and 9). The acute toxicity of phenols to mollusc larvae
was determined in two 48-hour exposures. The EC50 of phenol to
hard clam larvae was 58,250 y.g/1 and to American oysters, 52,630
ug/1 (Table 8; Davis and Hidu, 1969).
Chronic Toxicity
The chronic toxicity of phenol on saltwater plants, inverte-
brate and fish species has not been studied.
Miscellaneous
No data are available on the accumulation of phenol by salt-
water organisms or on effects not previously discussed.
B-21
-------
CRITERION FORMULATION
Saltwater - Aquatic Life
Summary of Available Data
The concentrations below have been rounded to two significant
figures.
Final Fish Acute Value = 620 ug/1
Final Invertebrate Acute Value = 960 ug/1
Final Acute Value = 620 ug/1
Final Fish Chronic Value = not available
Final Invertebrate Chronic Value = not available
Final Plant Value = not available
Residue Limited Toxicant Concentration = "not available
Final Chronic Value = not^available
0.44 *x Final Acute Value = 270 ug/1
No saltwater criterion can be derived for pheriol using the
Guidelines because no Final Chronic Value for either fish or
invertebrate species or a good substitute for either value is
available, and there are insufficient data to estimate a criterion
using other procedures.
R-22
-------
CO
I
to
CO
Table 7. Marine fish acute values for phenol (Brown, et al. 1967a)
Organism
Rainbow trout.
Salmo gairdneri
Bioaseay
Method*
S
Test
Cone . **
U
Time
(hra)
A8
LC50
(uq/ll
5,200
Adjusted
LCbO
(uq/1)
2.303
* S = static
** U = unmeasured
Geometric mean of adjusted values = 2.303 pg/1 ,t = 620 ng/1
-------
Table 8. Marine invertebrate acute values for phenol (Davis & Hidu, 1969)
CO
10
biaassay Test
Ora^Qi§nj Metijou*_ Cone.**
Eastern oyster (embryo), S U
Crassostrea virginica
Hard clam (embryo), S U
Mercenaria mercenaria
Adjusted
Time LC50 LCbO
j/ics), ^uc|/iL (uq/i|
48 58,250 49,338
-w | V
48 52,630 44,578
* S static
** U - unmeasured
46 898
Geometric mean of adjusted values 46,898 jig/1 ' = 960 yg/1
49
-------
CD
I
N)
in
Table 9. Other marine data for phenol
Organism *
Test
Duration Ettect
Result
(uq/i) RetereiiCfe
Mountain bass,
Kuhlia sandvicensis
Mountain bass,
Kuhlia sandvicensis
Mountain bass,
Kuhlia sandvicensis
96 hrs LC50
Acute Violent reaction
Acute Moderate reaction
6,014 Nunogawa. et al. 1970
20,000 Hiatt, et al. 1953
2,000 Hiatt, et al. 1953
* Species endemic to Hawaii
-------
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B-29
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B-30
-------
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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 aqueous effluents from in situ
fossil fuel processing technologies on aquatic systems.
Contract No. 77-C-04-3913.
B-33
-------
Mammalian Toxicology and Human Health Effects
Exposure
Introduction
Phenol is a high volume industrial chemical which is
largely used as an intermediate for the manufacture of other
chemicals. Phenol is also produced by biological processes
and is a by-product of combustion and some industrial processes,
Phenol is clear, colorless, hygroscopic, deliquescent,
crystalline solid at 25°C, 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
uses. 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 10 pounds per year in 1975
(Chem. Eng. News, 1975), about 90 percent of which was
used in the production of phenolic resins, caprolactam,
bisphenol-A, alkylphenols, and adipic acid (Chemical Profiles,
1972).
C-l
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Table 1
Chemical and Physical Properties of Phenol
(NIOSH, 1976)
Formula:
Molecular weight:
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) 4- 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
C-2
-------
It should be noted that analytical data for phenol
should be interpreted with caution. Many spectrophotometric
tests, specifically those following the methodologies in
Deichmann's 1942 review article, are positive for phenol
as well as a spectrum of substituted phenol compounds (Am.
Pub. Health Assoc., 1971; Ettinger, et al. 1951; Smith,
1976).
The National Organic Monitoring Survey (U.S. EPA, 1977)
reported finding unspecified concentrations of phenol in
2 out of 110 raw water supplies by GLC/MS. The Survey found
no phenol in any finished water supplies. The National
Commission on Water Quality (1975) reported from U.S. Geologi-
cal Survey data that the annual mean concentration of phenol
in the lower Mississippi River was 1.5 >ig/l with a maximum
of 6.7 )ag/l and a minimum of 0.0 ug/1. The International
Joint Commission (1978) reported finding <0.5 to 5 ug/1
phenol in the Detroit river between 1972 and 1977.
Phenol is also produced endogenously in the mammalian
intestinal tract through the microbial metabolism of 1-tyro-
sine and p-hydroxybenzoic acid (Harborne, 1964). In addi-
tion, exposures to benzene (Docter and Zielhuis, 1967) and
the ingestion of certain drugs (Fishbeck, et al. 1975) can
lead to increased phenol production and excretion.
C-3
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Ingestion from Water
During the National Organic Monitoring Survey (U.S.
EPA, 1977) phenol was found in only 2 of 110 raw water supplies,
as analyzed by gas-liquid chromatography and mass spectroscopy.
The presence of phenol was detected but not quantified.
No phenol was found in finished water supplies. The National
Commission on Water Quality (1975) reported an annual mean
' >*. '
concentration of 1.5 ug/1 of phenol in raw water from the
lower Mississippi River. At a water intake of 2 I/day,
this would result in a phenol intake of 3 ;jg/per son/day.
A 1974 derailment in southern Wisconsin resulted in
significant groundwater contamination by phenol (Delfino
and Dube, 1976; Baker, et al. 1978). Most families continu-
ed drinking their well water until it became unpalatable.
The maximum concentration of phenol in the contaminated
water which was actually ingested by the 39 victims is uncer-
tain. 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 (SGOT), bilirubin, crea-tinine, uric acid, glu-
cose, and cholesterol showed no significant abnormalities.
C-4
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Urinary free and conjugated phenol levels, six months after
each group's initial exposure, 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
ingestion of contaminated water, contributed to the phenol
found in the urine.
Prior to 1900, phenol was frequently ingested to commit
suicide (von Oettingen, 1949) . Reported lethal doses in
man ranged from 4.8 to 128.0 grams (Natl. Inst. Occup. Safety
Health, 1976).
Ingestion from Foods
Free and conjugated phenol is a normal constituent
of animal matter (Table 2). It is most likely formed by
microbial metabolism in the intestinal tract from 1-tyrosine
and p-hydroxybenzoic acid (von Oettingen, 1949; Harborne,
1964). There are no market basket surveys of free and conju-
gated phenol to allow an estimate for the daily dietary
intake of phenol. Lustre and Issenberg (1970) have reported
finding 7 mg/kg phenol in smoked summer sausage and 28.6
mg/kg in smoked pork belly.
Four medicinal preparations which could be expected
to contribute to the ingestion of phenol are presently on
the market. They are Cepastat Mouthwash, Cepastat Lozenges
((R) Merrell-National) containing 1.45 percent phenol; Chlora-
septic Mouthwash, containing 1.4 percent phenol; and Chlora-
septic Lozenges ((R) Eaton Laboratories), containing 32.5
mg total phenol (free phenol and sodium phenolate) per lozenge
with a total manufacturer's recommended dose of up to eight
C-5
-------
lozenges per day (Huff, 1978) . Because there is no control
over the intake of non-prescription drugs, some individuals
may consume considerably higher doses.
TABLE 2
Phenol Content of Normal Rabbit Tissues
(6 animals)
(Deichmann, 1944)
Tissue
Blood
CNS
Kidney
Lung
Liver
Muscle
Phenol (mg/kg)
Free Conjugated
0-0.7
0
0-1.0
0-2.3
0-0.9
0-1.6
0-0.5
0-1.8
0-0.5
0-3.4
1.1-5.5
0-1.8
Total
0-0.7
0-1.8
0-1.4
0-3.4
1.1-6.2
0-3.4
G.I. Tract Includ-
ing Contents
Heart, Spleen, Thymus,
Testes, Adrenals
Urine (24 hr/vol.)
Feces (24 hr)
0-3.0
0-2.3
0-0.3 0-1.0
0-3.9 11.5-100.0
0.4-5.3 1.4-8.0
0-4.4
0-1.0
11.5-100.0
1.8-11.7
The taste and odor of phenol, and especially some of
its derivatives, are noticeable at relatively low concentra-
tions (Table 3).
C-6
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TABLE 3
Taste and Odor Thresholds for Phenol in Water
TASTE
mg/1
>1
1
mg/1
>1
10
5
1
TEMPERATURE
C
ca.24
30
60
REFERENCE
Burttschell,
et al. 1959
Hoak, 1957
Hoak, 1957
Veldrye, 1972
A bioconcentration factor (BCF) relates the concen-
tration of a chemical in water to the concentration in aquatic
organisms, but BCF's are not available for the edible portions
of all four major groups of aquatic organisms consumed in
the United States. Since data indicate that the BCF for
lipid-soluble compounds is proportional to percent lipids,
BCF's can be adjusted to edible portions using data on percent
lipids and the amounts of various species consumed by Americans
A recent survey on fish and shellfish consumption in the
United States (Cordle, et al. 1978) found that the per capita
consumption is 18.7 g/day. From the data on the 19 major
species identified in the survey and data on the fat content
of the edible portion of these species (Sidwell, et al.
1974), the relative consumption of the four major groups
and the weighted average percent lipids for each group can
be calculated:
C-7
-------
Consumption Weighted Average
Group (Percent) Percent Lipids
Freshwater fishes 12 4.8
Saltwater fishes 61 2.3
Saltwater molluscs 9 1.2
Saltwater decapods 18 1.2
Using the percentages for consumption and lipids for each
of these groups, the weighted average percent lipids is
2.3 for consumed fish and shellfish.
Measured bioconcentration factors of 1.2 to 2.3 were
obtained with goldfish by Kobayashi, et al. (1976) and Kobayashi
and Akitake (1975) , but the exposures only lasted one to
five days. The equation "Log BCF = 0.76 Log P - 0.23" can
be used (Veith, et al. Manuscript) to estimate the BCF for
aquatic organisms that contain about eight percent lipids
from the octanol-water partition coefficient (P). Based
on an octanol-water partition coefficient of 31, the steady-
state bioconcentration factor for phenol is estimated to
be 8.0. An adjustment factor of 2.3/8.0 = 0.2875 can be
used to adjust the estimated BCF from the 8.0 percent lipids
on which the equation is based to the 2.3 percent lipids
that is the weighted average for consumed fish and shellfish.
Thus, the weighted average bioconcentration factor for phenol
and the edible portion of all aquatic organisms consumed
by Americans is calculated to be 8.0 x 0.2875 = 2.3.
Inhalation
The inhalation of phenol vapors appears to be largely
restricted to the occupational environment. Phenol vapor
is efficiently absorbed from the lungs. Piotrowski (1971)
administered phenol vapors to human volunteers wearing masks
C-8
-------
to minimize the effect of skin absorption. The phenol concen-
trations ranged from 6 to 20 mg/m . Piotrowski 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 exposure. Piotrowski did
not report finding any adverse effects in his subjects after
the exposures to phenol vapor.
Ohtsuji and Ikeda (1972) found up to 12.5 mg/m of
phenol vapors in bakelite factories. They reported no ad-
verse effects but confirmed that phenol was efficiently
absorbed through the lungs.
The present threshold limit value (TLV) is 20 mg/m
as a time weighted average (TWA) with a ceiling value of
60 mg/m (Natl. Inst. Occup. Safety and Health, 1976).
Dermal
The primary site of phenol absorption in industry is
the skin. The skin is a major route of entry for phenol
vapor, 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 (one percent
w/v) readily penetrate human skin (Roberts, et al. 1977).
As the phenol concentration increases the permeability coef-
ficient also increases. At very high concentrations of
phenol in water the resulting skin damage retards the absorp-
tion of phenol (Deichmann and Keplinger, 1963).
In addition to exposures from occupational sources,
a number of medicinal preparations can be sources of dermally absorb-
C-9
-------
ed phenol. A partial census of phenol-containing prepara-
tions for skin application follows. The quantities used
of these agents are not under control. Campho-Phenique
((R) Glenbrook) liquid, 4.75 percent phenol, powder/ 2 per-
cent; Calamine lotion, 1 percent phenol; P&S ointment or
liquid ( (R) Baker Laboratories) 1 percent phenol; Panscol
ointment ((R) Baker Laboratories) 1 percent phenol; Benadex
ointment ((R) Fuller) 1 percent phenol; Kip for Burns oint-
ment ((R) Young's 0.5 percent phenol; Noxzema Medicated
((R) Noxell) 0.5 percent phenol; Tanurol ointment ((R) O'Neal,
Jones & Feldman) 0.75 percent phenol; Dri Toxen cream ((R)
Walker Corp.) 1 percent phenol; Peterson's ointment ((R)
Peterson's Ointment Co.) 2.5, percent phenol. In addition,
some feminine hygiene products and hemorrhoidal products
contain phenol (Huff, 1978; Am. Pharma. 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, regardless of the route of administra-
tion. Twenty-four hours after administering 300 mg/kg phe-
nol orally to rabbits, Deichmann (1944) reported finding
less than one percent of the administered dose in the feces.
Piotrowski (1971) exposed human volunteers in climate
controlled inhalation chambers to phenol administered through
face masks to eliminate the influence of dermal exposures.
C-10
-------
He found that/ initially, an average of 80 percent of the
phenol was retained in the lungs. The percentage of retained
phenol dropped during the experiment, so that after six
to eight hours an average of only-70 percent of the phenol
was retained in the lungs. Subsequently, Piotrowski (1971)
exposed his volunteers for six to eight 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 for phenol vapor could be represented
by the formula A=(0.35)C, where A= 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)
are recalculated utilizing the efficiency of inhalation :
and the skin absorption coefficient reported by Piotrowski,
it can be demonstrated that the figures are confirmatory.
Distribution
Phenol is rapidly distributed to all tissues in animals
that have been poisoned with the compound. Within 15 min-
utes of an oral dose, the highest concentrations are found
in the liver, followed by heart, lungs, kidney, blood, and
muscle (Table 4) (Deichmann, 1944). As time progresses,
concentrations become fairly uniform and start to decrease
as the body begins to clear the phenol; 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
C-ll
-------
TABLE 4 .
Distribution of Phenol in.the Organs of Rabbits After an
Oral Dose of 0.5 g/kg
(from Deichmann, 1944)
Tissue
Phenol
Died
after
15 min.
Died
after
82 min.
Concentration of
Liver
Blood
Kidneys
Lungs
Heart,
Testes,
Thymus
Spleen
Brain &
Cord
Muscle
Urine
Phenol in
Free
Conjugated
Total
Free
Conjugated
Total
Free
Conjugated
Total
Free
Conjugated
Total
Free
Conjugated
Total
Free
Conjugated
Total
Free
Conjugated
Total
Free
Conjugated
Total
total
637
9
646
308
9
317
353
8
361
342
18
360
530
6
536
313
5
318
190
0
190
0
224
42
266
224
53
277
134
74
208
208
47
255
210
23
233
82
5
87
5
140
145
1
Killed
after
2 hrs.
Phenol in
34
32
66
58
80
138
48
228
276
54
67
121 .
68
57
125
68
7
75
92
11
103
7
Killed
after
2% hrs
mg/kg ti
135
60
195
113
102
215
112
129
241
122
51
173
140
51
191
104
3
107
120
8
128
116
520
636
1
Killed
after
6 hrs.
ssue
5
94
99
65
98
163
26
300
326
15
30
45
75
77
152
25
4
29
101
14
115
110
123
233
2
air exhaled
C-12
-------
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 for man, even though his
study did not provide distributional data for various organs.
Metabolism
Free and conjugated phenol appear to be normal trace
constituents of the human body and have also been found
in other mammalian species (Harborne, 1964). Values reported
for phenol concentrations in normal human blood differ markedly
among various investigators. Ruedemann and Deichmann (1953)
report normal blood values for free phenol at 1.5 mg/1 and
3.5 mg/1 for conjugated phenol. A brief list of "normal"
human blood values (Natl. Inst. Occup. Safety Health, 1976)
cites ranges for free phenol of none or traces to 40 mg/1
and conjugated phenol concentrations of 1 to 20 mg/1. The
variability appears to be due in part to the specificity
of the analytical method for phenol (Ikeda and Ohtsuji,
1969) , and to the amount of dietary protein which increases
urinary phenol excretion (Folin and Denis, 1915). More
recent values determined by gas-liquid chromatography are
0.04 to 0.56 mg/1 free phenol plus 1.06 to 5.18 mg/1 conjugated
phenols (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
background levels by exposure to agents which are normally
C-13
-------
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-Bismol (contains phenylsalicylate) resulted
in peak urinary phenol levels of 260 mg/1 in a human volun-
teer (Fishbeck, et al. 1975). The normal background concen-
tration for urinary phenol in this series was 1.5-5 mg/1
by gas layer 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/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 clear-
ly presented by Deichmann and Keplinger (1963) for a lethal
oral dose of 0.5 g/kg in rabbits and for a sublethal oral
dose of 0.3 g/kg in rabbits. These studies are summarized
in Figures 1 and 2.
There are some species differences in the metabolism
of phenol. Capel, et al. (1972) reported that man, rat,
mouse, jerboa, gerbil, hamster, lemming, and guinea pig
excreted four major metabolites: sulfate and glucuronic
acid conjugates of phenol and 1,4-dihydroxybenzene; the
squirrel monkey and the capuchin excreted phenyl glucuronide,
1,4-dihydroxybenzene glucuronide, and phenyl sulphate.
The ferret, dog, hedgehog, and rabbit excreted phenyl sulfate,
C-14
-------
1,4-dihydroxybenzene sulfate, and phenyl glucuronide. The
rhesus monkey, fruit bat, and chicken excreted phenyl sulfate
and phenyl glucuronide, but no 1,4-dihydroxybenzene conju-
gates. 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 inythis:study?... :^f--;\\ " "-f^l.'lbs-W ,: '..':' "..'
In man, the rate of .absorp^icy^'metabdlism and excre-
tion of phenol is relatively rapid. The absorbed phenol
was almost completely metabolized and excreted within 24
hours in inhalation experiments near the TLV (Piotrowski,
1971). . . '. ;..;>-,; ..-';..' '...'. '
Excretion ; ;' '. ' ':'.' ''" / ..".'"; .':';' '.
In man and all mammals tha't; have been tested, nearly
all of the phenol and its metabolites are excreted in the
urine. Only minor amounts are excreted in air and in the
feces (Figures 1 and 2) .Piptrows'ki; (3.971) studied the excre-
tion of phenol in human ..vo'luriteets "that had been exposed
C-15
-------
Rabbit.
Oral Dose
0.5 g/kg.
47%
Oxidized in
body to CO2
and water
plus traces of
1,4-dihydroxy-
benzene and
orthodihyd-
roxybenzene
Excreted
in urine
Remaining
in carcass
Exhaled
in air
Trace
Excreted
infeces
37%
63%
Excreted as
free phenol
Excreted as
conjugated phenol
Figure 1. Fate of a lethal oral dose of phenol analyzed
over 5 hours (Deichmann, 1942)
C-16
-------
Rabbit
Oral Dose
0.3 g/kg
Excreted
in urine
Oxidized in
body to C02
and water
plus traces of
1,4-dihydroxybenzene
and ortno-
di hydroxy benzene
Remaining
in carcass
rac
Exhaled
in air
Excreted
in feces
48%
Excreted as
free phenol
52%
Excreted as
conjugated phenol
50%
Conjugated
with
sulfuric acid
30%
Conjugated
with
glucuronic acid
Conjugated
with
other acids
Figure 2. Fate of a sublethal oral dose of phenol
analyzed over 24 hours (Deichmann, 1942)
C-17
-------
!3
i
2
16 30 24 4 a 12 16 20 2* 4 3
Tinw of doy (hr)
120
ICO
|-ao
bO
4O
20
alo
?
1
o
O
3
/
2.
Q
«
Figure 3: Concentrations and excretion rates of phenol in
urine in a subject exposed to phenol vapor in a concentra-
tion of 18.3 mg/m by inhalation (from Piotrowski, 1971).
-7.. O Z 4 6 a 10 12 14 16 13 2O 22 24
Hours from irqrr of exooiura
Figure 4: Excretion rate of "excess phenol in relation to
absorption. Means S.D. Dotted line - theoretical curve
for K=0.2 hour . TFrom Piotrowski, 1971).
C-18
-------
to phenol through inhalation or skin absorption. He found
that the human body behaved almost like a single compartment
with respect to phenol absorption and clearance, with an
excretion rate constant of K=0.2 hrs.~ . This corresponds
to a half life of approximately 3.5 hours (Figures 3 and
4). The half life is defined as t%= 0.693.
K
EFFECTS
Acute, Sub-acute, and Chronic Toxicity
Regardless of the route of administration, the signs t
and/or symptoms of acute toxicity in man and experimental
animals are similar. 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 initiated by
muscular twitchings and severe convulsions. The USSR litera-
ture reference in the National Institue for Occupational
Safety and Health phenol criterion document reported finding
changes in sensitivity to light after five minute exposures
at 15.5 yg/m and changes in the formation of conditioned
reflexes at 15.5
After the absorption of an acutely toxic dose the heart
rate first increases and then becomes slow and irregular.
After an initial 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 respiratory arrest (Deichmann and
Keplinger, 1963; Sollmann, 1957). The approximate median
lethal doses (LD5Q) for phenol in various species dosed
C-19
-------
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 seems to be the most sensitive species,
which seems to be a consequence of its metabolism of phenol.
It is difficult to estimate the LDcQ of oral 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 assuming a bodyweight of 70 kg.
When the data in Tables 5 and 6 are compared, it becomes
evident 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
pathological changes associated with acute exposures to
phenol:
The pathological changes produced by phenol in
animals vary with the route of absorption, vehicle
employed, concentration,.and duration of exposure.
Local damages to the skin include eczema, inflammation,
discoloration, papillomas, necrosis, sloughing, and
gangrene. Following oral ingestion the mucous membranes
of the throat and esophagus may show swelling, corrosions,
and necroses, with hemorrhage and serious infiltration
of the surrounding areas. In a severe intoxication
the lungs may show hyperemia, infarcts, bronchopneumonia,
purulent bronchitis, and hyperplasia of the peribronchial
tissues. There can be myocardial degeneration and
necrosis. The hepatic cells may be enlarged, pale,
and coarsely granular with swollen, fragmented, and
pyknotic nuclei. Prolonged administration of phenol
may cause parenchymatous nephritis, hyperemia of the
glomerular and cortical region, cloudy swelling, edema
of the convoluted tubules, and degenerative changes
of the glomeruli. Blood cells become hyaline, vacuolated,
or filled with granules. Muscle fibers show marked
striation.
C-20
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TABLE 5
The Acute Toxicity of Phenol to Non-human Mammals'
Species
Cat
Cat
Dog
Guinea
Pig
Mouse
Rabbit
Rabbit
Rabbit
Rabbit
Rabbit
Rat
Rat
Rat
Rat
Rat
Rat
ain dilute
Route
Subcut.
Oral
Oral
Subcut.
Subcut
Intrav.
Subcut.
Oral
Oral
I. P.
Subcut.
Oral
Oral
I. P.
Dermal
Dermal
aqueous
Dose killing
approx. 50%
g/kg
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
2.5
0.67
solution, unless
Reference
Tollens, 1905
Macht, 1915
Macht, 1915
Duplay & Cazin, 1891
Tollens, 1905
Deichmann & Witherup,
Tauber, 1895; Tollens
Clarke & Brown, 1906
Deichman & Witherup,
Deichmann & Witherup,
Deichmann & Witherup,
Deichmann & Witherup,
.) Deichmann & Witherup,
1944
, 1905
1944
1944
1944
1944
1944
oil) Farquharson, et al. 1958
Deichmann & Witherup,
Conning & Hayes, 1970
noted otherwise.
1944
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-21
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In addition, the urine is usually dark or "smoky" in
appearance, probably due to oxidation products of phenol.
The urine may darken further upon standing (Sollmann, 1957).
The symptoms reported by humans that had consumed phenol
contaminated 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.
TABLE 7
Symptom Distribution of Cases and Controls After Ingestion
of Well Water Contaminated by Phenol
(Baker, et al. 1978)
Symptom
(N = 39)
Vomiting
Diarrhea
Headache
Skin rash
Mouth sores
Paresthesia or numbness
Abdominal pain
Dizziness
Dark urine
Burning with urination
Fever
Back pain
Burning mouth
Shortness of breath
Percentage of
Study Group
(N = 119)
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 with
Control Group
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
*Significantly greater than controls,? .01, Fishers Exact
test.
Not associated with phenol exposure in previous medical
reports.
C-22
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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. This corresponded to an average
daily intake of 0, 21, 30, 49, 56, and 55 mg of phenol per
rat per day based on actual water consumption data. At
the end of the experiment there were no significant differences
in tissue phenol levels of the control and experimental
rats. The weight gain of the rats at the two highest dose
levels was depressed. A daily oral dose of 56 mg per rat
is approximately 30 percent 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 demonstrated by the fact that the rats that ingested
the highest daily amount consumed, over a one-year period,
the equivalency of approximately 120 LD5Q 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, below.
TABLE 8
The Effect of Phenol Solutions Upon Rats
(Heller and Pursell, 1938)
Phenol Growth
Drinking
Solutions
mg/1
ReproductionComments
5 generations
5 generations
5 generations
3 generations
3 generations
2 generations
2 generations
Retarded
None
500
1,000
3,000
5,000
7,000
8,000
10,000
12,000
Normal
Normal
Normal
Normal
Normal
Below normal
Fair
Retarded
Retarded
Splendid condition
Appearance good
Food & water intake satisfact,
General appearance good
General appearance good
Stunted growth in young
Many young died
Young not cared for
Old died in hot weather
C-23
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In an unpublished study by Dow Chemical Company (1976)
rats were fed 20 daily doses of 0.1 g/kg phenol by gavage.
These rats showed slight liver and kidney effects, while
rats which received 20 daily doses of 0.05 or 0.01 g/kg
phenol demonstrated none of those effects. In a subsequent
series of tests, rats received 135 doses of 0.1 or 0.05
g/kg phenol by gavage over a six month period. The growth
of the rats 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/kg phenol.
The feeding of 0.05 g/kg of phenol 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 phenyl-
salicylate is metabolized to phenol, this resulted in uri-
nary 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) . \
Synergism and/or Antagonism
No significant evidence could be found to support the
occurrence 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.
C-24
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Teratogenicity
The work by Heller and Pursell (1938) which has been
discussed previously, demonstrated no significant effects
on reproduction in rats receiving 100 to 5,000 mg/1 phenol
in their drinking water over three to five generations.
This study was, however, not designed specifically as a
teratogenicity study.
Mutagenicity
Demerec, et al. (1951) reported that phenol produced
back-mutations in E._ coli from streptomycin dependence to
non-dependence. Significant back-mutations occurred at
0.1 to 0.2 percent 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 non-
mutagenic for Neurospora. Hadorn and Niggli (1946) found
phenol mutagenic in Drosophila after exposing the gonads
°f Drosophila to phenol ir± vitro.
The existing information on the mutagenicity of phenol
is equivocal and needs to be reexamined 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
that had been exposed to a single dose of the initiator
9,10-dimethyl-l,2-benzanthracene (DMBA) by skin painting
followed by repeated dermal applications of selected phenols.
In one experiment in this series, mice which had been spe-
cially inbred for sensitivity to develop tumors, after initia-
tion with DMBA and promotion by croton oil through skin
C-25
-------
painting, received a single application of 75 jug DMBA to
the clipped skin. This was followed one week later by twice
weekly applications of 2.5 mg phenol applied to the skin
as a ten percent solution in benzene repeatedly for 42 weeks.
The mice receiving this dose and concentration 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 had papillomas
(36 percent) after 52 weeks. The skin painting with phenol
was continued until the 72nd week at which time one fibrosar-
coma was diagnosed. Other strains of mice, Holtzman, CAF-^
and C3H, also produced papillomas after initiation with
DMBA and subsequent skin painting with ten 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 pre-treatment
with DMBA. Tests with a 20 percent phenol solution (5 mg/mouse)
caused a number of deaths due to systemic toxicity.
Salaman and Glendenning (1957) reported that "S" strain
albino mice showed strong promoting activity for tumor forma-
tion after initiation with 0.3 mg DMBA followed by repeated
skin applications of 20 percent phenol. Twenty percent
phenol solutions produced significant damage to the skin
C-26
-------
and were mildly carcinogenic when applied alone. Phenol
in a five percent solution had a moderate promoting effect
but was not carcinogenic without previous initiation.
VanDuuren, et al. (1971) found phenol (3mg/mouse, 3x/week)
in ICR/Ha Swiss mice to have only slight promoting activ-
ity after initiation with benzo(a)pyrene (BaP). In subse-
quent experiments VanDuuren, et al. (1973) demonstrated
that phenol is not cocarcinogenic since, when it is applied
together with BaP repeatedly, tumorogenesis is inhibited
slightly. This partial inhibitory effect in cocarcinogene-
sis experiments was subsequently confirmed by VanDuuren
and Goldschmidt (1976).
In conclusion, phenol appears to have tumor promoting
activity in many strains of mice when repeatedly applied
to the clipped skin after initiation with known carcinogens.
The tumor-promoting activity is highest at dose levels of
phenol which have some sclerosing activity but also occurs
in sensitive strains at phenol concentrations which do not
produce obvious skin damage. Phenol has no cocarcinogenic
activity when applied simultaneously and repeatedly together
with BaP to mouse skin, but it reduces the incidence of
tumor formation slightly. Phenol has carcinogenic activity
when applied repeatedly to the skin of a specially bred
strain of Sutter mice, especially at concentrations which
produce repeated skin damage. Phenol has not been found
to be carcinogenic when applied alone to the skin of
standard strains of mice.
C-27
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While the existing qualitative data derived from skin
painting in one sensitive strain of mice provide weak sus-
picion for a carcinogenic response to phenol, the protocol
was found, in agreement with NIOSH, to be inappropriate
and inadequate for the purpose of judging phenol to be a
carcinogen in drinking water.
C-28
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CRITERION FORMULATION
Existing Guidelines and Standards
In 1974, the Federal standard for phenol in air in
the workplace was 19 mg/m or 5 ppm as a time weighted average
(39 FR 125). This coincided with the recommendation of
the American Council for Governmental Industrial Hygienists
(1977). The NIOSH (1976) criteria for a recommended standard
for occupational exposure to phenol are 20 mg/m in air
as a time weighted average for up to a ten hour work day
and a 40-hour work week, with a ceiling concentration of
60 mg/m 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 objectionable taste and odor produced by chlorinated
phenols. In response to a phenol spill in Southern Wiscon-
sin, the U.S. EPA'proposed on November 26, 1974 an 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)
reported finding unspecified concentrations of phenol in
2 out of 110 raw water supplies. The Survey found no phenol
in any finished water supplies. The National Commission
on Water Quality (1975) reported that the annual mean phenol
concentration in the lower Mississippi Rirver was 1.5jug/l
in 1973, with a maximum of 6.7 /ag/1.
C-29
-------
Endogenously produced phenols in man occur at signifi-
cantly higher concentration than this. They result in total
urinary free and conjugated phenol concentrations ranging
from 5 to 55 mg/1.
Occupational exposures at a TLV of 20 mg/m TWA would
result in the absorption of 105 mg phenol from the inspired
air, assuming moderate to low activity (7 m air breathed
per 8 hours)/ and an absorption efficiency of 75 percent.
During heavier activity (equivalent to 20 m /8 hours) the
absorption would rise to 300 mg phenol for an eight 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 exposed to phenol at 10,000. This reflects the number
of people that are employed in the production of phenol,
formulation into products, or distribution of concentrated
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 chem-
ists, pharmacists, biomedical personnel, and other occupa-
tions.
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/1 of phenol in drinking water for five genera-
tions and at 3,000 and 5,000 mg/1 for three generations.
Assuming a daily water intake of 30 ml and an average body
C-30
-------
weight of 300 grams, these rats would have received daily
doses of 10, 50, 100, 300, and 500 mg/kg/day. The upper
range approaches a single LD5Q dose per day. Deichmann
and Oesper (1940) reported no significant effects in rats
receiving approximately 70, 100, or 163 mg/kg/day in their
drinking water for 12 months. However, both of these studies
did not report detailed pathological or biochemical studies
but relied mostly on the weights and the 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/kg/dose resulted in some liver and kidney damage.
At 50 mg/kg/dose the exposure resulted in only slight kidney
damage. It must be borne in mind that in the first two
studies the phenol is incorporated into the drinking water
so that the daily dose is taken gradually. In the Dow study
the phenol is administered 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. 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 (Table
%
9). Consequently, an intermediate 500X uncertainty factor
was selected.
C-31
-------
TABLE 9
Guidelines for Using Uncertainty Factors
(NAS Drinking Water and Human Health, 1977)
Uncertainty Factor = 10
Uncertainty Factor = 100
Uncertainty Factor = 1,000
Valid experimental results
from studies on prolonged
ingestion by man, with no
indication of carcinogenicity.
Experimental results of
studies of human ingestion
not available or scanty
(e.g., acute exposure only).
Valid results of long-
term feeding studies
on experimental animals or
in the absence of human
studies, valid animal studies
on one or more species.
No indication of carcinogenicity,
No long term or acute
human data. Scanty results on
experimental animals.
No indication of carcinogenicity.
C-32
-------
When one examines the amount of phenol absorbed through
inhalation near the TLV of 20 mg/m for occupational expo-
sures by using the Stokinger and Woodward model (1958),
then at a breathing rate of 10 m for an eight hour day
with 15 percent absorption and a body weight of 70 kg,
a man would absorb approximately 2.14 mg/kg/working day,
assuming no skin absorption. The use of the Stokinger-Woodward
model may be applicable to estimate acceptable intake from
water.
«
It has been established that phenol is absorbed rapidly
by all routes and subsequently is distributed rapidly.
If a tenfold safety factor is applied to the projected doses
absorbed from inhalation 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 chronic 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, assuming
a 70 kg body weight. Therefore, assuming 100 percent gastro-
intestinal absorption of phenol, and consuming 2 liters
of water daily and 18.7 grams of contaminated fish having
a bioconcentration factor of 2.3, would result in a maximum
permissible concentration of 3.4 mg/1 for the ingested water:
The equation for calculating the criterion for the phenol
content of water given an Acceptable Daily Intake is
2X = (0.0187) (F) (X) = ADI
C-33
-------
Where
2 = anount of drinking water, liter/day
x = phenol concentration in water, mo/I
0.0187 = amount of fish consumed, kg/day
F = bioconcentration factor, mg phenol/ka fish
per rog phenol/1 water
ADI = limit on daily exposure for a 70 kg person
2X + (0.0187) (2.3)X = 7.0
X = 3.4 mg/1
This water qualitv criterion is in the ranqe of reported
taste and odor threshold values for phenol reported in Table 3.
It must be noted that this value has been derived for unchlorinated
phenol.
It is reeocmized that when ambient water containina this concen-
tration of phenols is chlorinated, various chlorinated rhenols may
be produced in sufficient Quantities to produce obiectional taste and
odors (See Introduction). 2-Chlorophenol and 2,4-dichlorophenol
have been reported to exhibit a. threshold of unfavorable odor in water
at concentrations of 0.33 uq/1 and 0.65 uq/'l, respectively. Consequently,
criteria of 0.3 uq/1 and 0.5 uq/1 were published in the Federal Reqister
on March 15, 1979 (44 PR 15926), for these two chlorophenols.
In viaw of the fact that the orqanoleptic properties of phenol mav
be greatly potentiated through the inadvertent chlorination of phenol-
contaminated water, the phenol concentration in water should not exceed
1.0 ug/1 in those instances where such inadvertent chlorination may
take place.
C-34
-------
In summary, based on the use of chronic toxicologic test data
for rats and an uncertainty factor of 500, the criterion for phenol
corresponding to the calculated acceptable daily intake of 0.1 my/kg/
day is 3.4 mg/1. Drinking water contributes 98 percent of the assumed
exposure while eating contaiminated fish products accounts for two
percent. The criterion level could alteratively be expressed as 163 mg/1
if exposure is assumed to be from the consumption of fish and shellfish
products alone.
Based on the potential chlorination of phenol in water, the criterion
for phenol is 1.0 ug/1 in those instances where such inadvertent chlorination
may take place.
C-35
-------
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