TOXICOLOGICAL PROFILE FOR
ORTHO-CRESOL
Criteria and Standards Division
Office of Drinking Water
U.S. Environmental Protection Agency
Washington, DC 20460
August 1989
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August 1989
TOXICOLOGICAL PROFILE
FOR
ORTHO-CRESOL
Criteria and Standards Division
Office of Drinking Water
U.S. Environmental Protection Agency
Washington, DC 20460
-------
ORTHO-CRESOL
A. GENERAL
1. CAS Number: 95-48-7
2. RTECS Number: G06300000
3. General Name/Synonyms; 2-Methyl phenol
o-Cresylic acid
o-Hydroxytoluene
4. Molecular Formula: C7H80
5. Molecular Weight; 108.14
6. Structure:
B. PHYSICAL AND CHEMICAL PROPERTIES
1. State: Colorless liquid; becomes dark
with age and exposure to
air/light
2. Vaoor Pressure: 1 mm Hg at 38.2°C.
Windholz et al. (1983)
Sax (1975)
3. Melting Point; 30°C
Windholz et al. (1983)
4. Boiling Point; 191-192°C
Windholz et al. (1983)
5. Specific Gravity; 1.047 at 20°C
Windholz et al. (1983)
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6. Solubility; Soluble in alcohol, ether, Sax and Lewis (1987)
chloroform; and
2.5g/100 mL water Windholz (1976)
at 25°C
7. Log Ka...: 1.95 Leo et al. (1971)
8. UV Absorption: No information was found.
C. PHYSICAL/CHEMICAL EQUILIBRIUM FACTORS
1. Bioconcentration Factors (BCF): No information was found.
2. Kwa: No information was found.
3. K,,.: No information was found.
D. ENVIRONMENTAL FATE
1. Photolysis; Direct photolysis of o-cresol in water at 254 nm gave the
following detectable products (Joschek and Miller 1966):
OH
o-er*so1
However, the analytical method used in these experiments provided
qualitative identification of only phenolic products (Smith et al.,
1978).
2. Leaching; Cresols are adsorbed weakly onto soils and organic matter
(Smith et al., 1978) and will readily leach into the aquatic
compartment.
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3. Route of Water Contamination: o-Cresol is likely to enter the aquatic
compartment from a number of sources; the major release probably is
industrial wastewater.
Bartle et al. (1977) utilized injections into a Tenax precolumn followed
by gas chromatography to analyze an industrial effluent before and after
an unspecified waste treatment process. The o-cresol concentrations
were 12 ppm and <1 ppm, respectively.
Baird et al. (1977) analyzed wastewater discharges from a petroleum
refinery and reported a concentration of 5482 ppm o-cresol. Sampling
further downstream in the trunk sewer system revealed concentrations of
118 and 21.8 ppm. On another sampling occasion, the following
concentrations were reported for o-cresol: 418 ppm from the same
refinery discharge and 34.2 ppm in the sewer downstream.
4. Hydrolysis: No information was found.
5. Plant Uptake: No information was found.
6. Microbial Degradation: The biological degradation of o-cresol by
adapted activated sludge was determined by measuring the decrease in
chemical oxygen demand (COD) (Pitter, 1976). Following 120 hours of
incubation at 20 ± 3°C, 95.0% of the initial COD was removed. The rate
of biodegradation was calculated as 54.0 mg COD/g of dry matter of the
activated sludge/hour. o-Cresol was considered to be biologically ready
to decompose.
In a study designed to model anaerobic aquatic systems, such as heavily
polluted waters or waste lagoons, o-cresol at concentrations of 1 and 50
ppm was completely degraded in about 7 and 15 days, respectively, at
ambient temperatures. The rate of degradation decreased at lower
temperatures (Ettinger et al., 1951).
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Semov and Andreeva (1972) treated wastewater discharged from a coke-
chemical plant with increasing concentrations of phenol over a period of
8 months. A total of 309 strains were isolated from the activated
sludge. Five microbes completely metabolized o-cresol at a
concentration of 100 ppm in 2 to 4 days at a dilution of 1:20 cresol to
wastewater. At increased concentrations o-cresol (1:5), 21 strains were
able to completely oxidize cresol. These studies indicate that microbes
adapt to various chemical effluents by a gradual change in their
metabolic behavior and/or by selection.
7. Persistence in Soil/Water: No information was found.
8. Byproducts; A summary of possible o-cresol biodegradation pathways,
under aerobic conditions, based on whole cells or cell-free extracts
from pure cultures, is presented in Figure 1. This scheme depicts the
pathways for Pseudomonas sp and Bacillus stearothermoohilus that are
known to degrade o-cresol.
(1,2,3)
o-crtsol
CM,
3-nathylMtKhol
2-hydrox/-6-
oxohepu-2,4-
dlenoic »e1d
CH.COOH
""«
""
. , ..
a, 3, 4).
CH,.C-COO'
C pyrmatt
and
CHj-CHO
actuldvhyd*
4-hydro»y-2-o»o-
vtltric tcid
(1) Bayly et al. (1966) Pseudomonas sp
(2) BusweII (1975) Bacillus stearothermophilus
(3) Ribbons (1966) Pseudomonas aeruginosa
(4) Feist and Hegeman (1969) Pseudomonas sp
Figure 1. Degradation of o-cresol by pure
cultures or cell-free extracts of microorganisms.
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9. Vaporization; No information was found.
E. ACUTE TOXICITY IN MAMMALS
Animal/strain/sex Route
LDSO (nig/kg)
Reference
Rat/-V-
Oral
1350
Diechmann and Witherup
(1944)
Rat/Wistar/M,F
Rabbi t/-/-
Rabbit/New Zealand
White/F
Oral
Dermal
Dermal
360
>2000
890
(460-1690)"
Bailey (1982a)
Bailey (1982b)
Vernot et al . (1977)
"Data not provided.
"95% confidence limits.
F. SKIN AND EYE IRRITATION AND SENSITIZATION IN MAMMALS
No information was found.
G. SUBCHRONIC TOXICITY IN MAMMALS
Groups of 30 male and 30 female Sprague-Dawley rats were administered, by
gavage, o-cresol (99.5% pure) in corn oil at 0, 50, 175, or 600 mg/kg/day for 13
consecutive weeks. Animals were examined twice daily, and body weight and food
consumption were measured weekly. Ophthalmologic examinations were conducted
before dosing and at termination. Batteries of hematological, clinical
chemistry, and urinalysis tests were administered prior to study initiation, at
study week 7, and at termination. At termination, all rats underwent gross
necropsy, and the heart, liver, spleen, brain, kidneys, gonads, adrenals, and
thyroid/parathyroid were weighed. Histopathological examinations of tissues
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from all control, mid-dose, and high-dose groups were conducted. Rats at the
high-dose level (600 mg/kg/day) exhibited signs of central nervous system (CMS)
depression that included lethargy, tremors, and coma; 9 males and 19 females
died during the study. Approximately 1-hour postdosing, the surviving animals
"recovered" and appeared normal. No other significant clinical signs were
observed in treated rats. Statistically significant (p <0.05) reductions in
body weight gain were seen in males during study weeks 2 through 10; a similar
effect was not observed in females. The mean food consumption values of males
at this level were significantly (p <0.05) lower than control values during
study weeks 1 through 6. At the mid-dose level (175 mg/kg/day), one female
exhibited lethargy and tremors on day 27 of the study; these signs were not
observed at any other time. Male rats at this level exhibited significant (p
<0.05) reductions in body weight during week 2 only. No treatment-related
effects were observed in rats given 50 mg/kg/day. Clinical chemistry,
hematology, opthalmology, urinalyses, and organ weight measurements did not show
any treatment-related changes. Histopathological examinations did not identify
o-cresol target organs. Thus, the cause of death among the high-dose animals
was not established. o-Cresol exerted central nervous system effects only at
the high dose. (Dietz and Mulligan, 1988).
H. REPRODUCTIVE EFFECTS AND TERATOGENICITY IN MAMMALS
No information was found.
I. MUTAGENICITY/GENOTOXICITY
Data are presented in tabular form on page 8.
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I. HUTAGENICITY/GENOTOXICITY
Test
Strain
Activation
Dose/concentrati on
Toxic effects
Reference
Ames mutagenicity
assay
Salmonella +S9
tvnhimurium
TA98, TA100,
TA1535, TA1537,
TA1538
0. 0.01, 0.1, 1.0,
5.0. 10.0. 25.0.
and 50.0 /([./plate
No mutagenicity
detected with or
without metabolic
activation.
o-Cresol was toxic
to all strains at
>10 Ml/plate
Jagarmath (1981)
Ames mutagenicity
assay
Forward mutation
assay
S. typhlmurium
TA98, TA100,
TA1535. TA1537
Mouse lymphoma
cell LS178Y
TK+/-
»S9
+S9
0, 1.0, 3.3, 10.0,
33.0, and 100.0 /ig/
plate
0, 3.91, 7.81,
15.6, 31.3, and 62.5
nL/ml
Non mutagenic
with or without
activation.
Nomutagenic
with or without
activation.
Haworth et al. (1983)
Cifone (1981)
I
-J
I
Sister chromatid
exchange (SCE)
Chinese hamster
ovary cells
-S9
+S9
Sister chromatid
exchange
Hunan
fibroblasts
(in vitro)
-S9
None
0, 15.6, 31.3, 62.5,
125.0, and 250.0
nL/mL
0, 0.56, 3.13,
6.25, 12.5. and
15.0 nL/mL
0, 12.5, 25.0, 50.0.
75.0, and 100.0 nL/mL
0. 0.8, 4. 8. 10.
and 30 nM
Significant
(p <0.1) dose-
related increase
in SCE both with
and without
activation.
At 8.0 nM,
significant (p <0.05)
increase in SCE
frequency; doses of
10 or 30 nM were
toxic.
Galloway (1981)
Cheng and Kligerman
(1984)
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I. MUTAGENICITr/GENOTOXICITY (continued)
Co
I
Test
Sister chromatic!
exchange
Unscheduled DNA
synthesis
Strain Activation
Bone marrow. None
alveolar macro-
phages. and
regenerating
liver cells of
DBA/male mice
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J. CHRONIC TOXICITY/CARCINOGENICITY
Animal
Strain Sex Route Dose
Treatment
Effects
Reference
Mouse
Sutter
Dermal 20X(IV/V)
Mice received
a single dermal
application of
25 1L of 0 3%
9.10-dimethyl -
1,2-benzanthracene
After 12 weeks
of treatment, skin
papillomas devel-
oped in 10 of 17
surviving mice,
no skin papillomas
in acetone followed were seen in the
by twice weekly
applications of
25 1L of 20X
o-cresol in
benzene for 12
weeks
vehicle (benzene)
control. Study
was terminated at
12 weeks
Boutwell and Bosch
(1959)
K. PHARMACOKINETICS IN MAMMALS
Bray et al. (1950) administered the cresols (250-500 mg) in NaHC03
solutions to rabbits (number, strain, and sex not specified) by gavage and
recovered 65-80% of the doses as free and conjugated cresols in the urine
within 24 hours of dosing. The results indicate that at least 65-80% of the
dose was absorbed from the gastrointestinal tract. In rabbits, of the 500 mg
of o-cresol administered by gavage, 15% was recovered in the urine as ethereal
sulfate and 72% as ether glucuronide. A minor metabolite detected after
administration of o-cresol was conjugated dihydroxytoluene. Approximately 80%
of the o-cresol administered was recovered in the urine within 24 hours
postdosing.
L. HUMAN HEALTH EFFECTS
No information was found.
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M. EXISTING STANDARDS/CRITERIA
Type Standards/Criteria Proponent Reference
TLV-TWA'
PEL"
IDLHC
5 ppm (?22 mg/m3)
5 ppm (?22 mg/m3)
250 ppm
ACGIH
NIOSH/OSHA
NIOSH/OSHA
ACGIH (1988)
NIOSH/OSHA (1978)
NIOSH/OSHA (1978)
"Threshold Limit Value-Time Weighted Average.
"Permissible Exposure Level.
'Immediately Dangerous to Life or Health.
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