TECHNICAL REPORT DATA
(fttttf rt»d /ntovctioni on the rtvent before completing!
^. REPORT NO.
EPA/600/8-89/095
4. TITLE AND SUBTITLE
a.
Updated Health Effects Assessment for Phenol
3. RECIPIENT'S ACCESSION NO
PB90-142472/AS
6. REPORT DATE
. PERFORMING ORGANIZATION CODE
'. AUTHOR(S)
I. PERFORMING ORGANIZATION REPORT NO
B. PERFORMING ORGANIZATION NAME AND ADDRESS
10. PROGRAM ELEMENT NO.
11. CONTRACT /GRANTNO.
12. SPONSORING AGENCY NAME AND ADDRESS
13. TYPE OF REPORT AND PERIOD COVERED
Environmental Criteria and Assessment Office
Office of Research and Development
U.S. Environmental Protection Agency
Cincinnati. OH 45268
14. SPONSORING AGENCY CODE
EPA/600/22
IS SUPPLEMENTARY NOTES
16. ABSTRACT
This report summarizes and evaluates information relevant to a preliminary interim
assessment of adverse health effects associated with specific chemicals or compounds.
The Office of Emergency and Remedial Response (Superfund) uses these, documents in
preparing cost-benefit analyses under Executive Order J2991 for decision-making under
CERCLA. All estimates of acceptable intakes and carcinogenic potency presented in
this document should be considered as preliminary and reflect limited resources
allocated to this project. The intent in these assessments is to suggest acceptable
exposure levels whenever sufficient data are available. The interim values presented
reflect the relative degree of hazard associated with exposure or risk to the
chemical(s) addressed. Whenever possible, two categories of values have been
estimated for systemic toxicants (toxicants for which cancer is not the endpoint of
concern). The first, RfD$ or subchronic reference dose, is an estimate of an exposure
level that would not be expected to cause adverse effects when exposure occurs during
a limited time interval. The RfD is an estimate of an exposure level that would not
be expected to cause adverse effects when exposure occurs for a significant portion
of the lifespan. For compounds for which there is sufficient .evidence of
carcinogenicity, qj*s have been computed, if appropriate, based on oral and
inhalation data if available.
KEY WORDS AND DOCUMENT ANALYSIS
DESCRIPTORS
b.lDENTIFIERS/OPEN ENDED TERMS C. COSATI Field/Group
11. DISTRIBUTION STATEMENT
Public
19. SECURITY CLASS (THuKtponi
Unclassified
21. NO. Of PAGES
20. SECURITY CLASS fThij jMft)
Unclassified
22. PRICE
PA F«n» 2220-1 (>*. 4-77) PRCVIOUI EDITION i» OMOLKTC
-------
EPA/600/8-89/095
3uly, 1989
HEALTH EFFECTS ASSESSMENT
FOR PHENOL
ENVIRONMENTAL CRITERIA AND ASSESSMENT OFFICE
OFFICE OF HEALTH AND ENVIRONMENTAL ASSESSMENT
OFFICE OF RESEARCH AND DEVELOPMENT
U.S. ENVIRONMENTAL PROTECTION AGENCY
CINCINNATI, OH 45268
-------
DISCLAIMER
This document has been reviewed 1n accordance with the U.S. Environ-
mental Protection Agency's peer and administrative review policies and
approved for publication. Mention of trade names or commercial products
does not constitute endorsement or recommendation for use.
11
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PREFACE
This report summarizes and evaluates Information relevant to a prelimi-
nary Interim assessment of adverse health effects associated with phenol.
All estimates of acceptable Intakes and carcinogenic potency presented In
this document should be considered as preliminary and reflect limited
resources allocated to this project. Pertinent toxlcologlc and environ-
mental data were located through on-Hne literature searches of the TOXLINE,
CANCERLINE and the CHEMFATE/DATALOG data bases. The basic literature
searched supporting this document Is current up to May 1987. Secondary
sources of Information have also been relied upon 1n the preparation of this
report and represent large-scale health assessment efforts that entail
extensive peer and Agency review. The following Office of Health and
Environmental Assessment (OHEA) sources have been extensively utilized:
U.S. EPA. 1980a. Ambient Water Quality Criteria Document for
Phenol. Prepared by the Office of Health and Environmental Assess-
ment, Environmental Criteria and Assessment Office, Cincinnati, OH
for the Office of Water Regulations and Standards, Washington, DC.
EPA-440/5-80-066. NTIS PB 81-117772.
U.S. EPA. 1987. Health and Environmental Effects Profile for
Phenol. Prepared by the Office of Health and Environmental Assess-
ment, Environmental Criteria and Assessment Office, Cincinnati, OH
for the Office of Solid Waste and Emergency Response, Washington,
DC. EPA/600/X-87/121. NTIS PB 89-132112/AS.
U.S. EPA. 1988. Integrated Risk Information System {IRIS).
Reference dose (RfD) for oral exposure for phenol. Online.
(Verification date 11/16/88). Office of Health and Environmental
Assessment, Environmental Criteria and Assessment Office,
Cincinnati, OH.
The Intent In these assessments Is to suggest acceptable exposure levels
for noncardnogens and risk cancer potency estimates for carcinogens
whenever sufficient data were available. Values were not derived or larger
uncertainty factors were employed when the variable data were limited In
scope tending to generate conservative (I.e., protective) estimates.
Nevertheless, the Interim values presented reflect the relative degree of
hazard or risk associated with exposure to the chemical(s) addressed.
Whenever possible, two categories of values have been estimated for
systemic toxicants (toxicants for which cancer Is not the endpolnt of
concern). The first, RfD$ (formerly AIS) or subchronlc reference dose, Is
an estimate of an exposure level that would not be expected to cause adverse
effects when exposure occurs during a limited time Interval (I.e., for an
Interval that does not constitute a significant portion of the llfespan).
111
-------
This type of exposure estimate has not been extensively used, or rigorously
defined, as previous risk assessment efforts have been primarily directed
towards exposures from toxicants 1n ambient air or water where lifetime
exposure Is assumed. Animal data used for RFD$ estimates generally
Include exposures with durations of 30-90 days. Subchronlc human data are
rarely available. Reported exposures are usually from chronic occupational
exposure situations or from reports of acute accidental exposure. These
values are developed for both Inhalation (RfD$i) and oral (RfOgo)
exposures.
The RfD (formerly AIC) 1s similar In concept and addresses chronic
exposure. It Is an estimate of an exposure level that would not be expected
to cause adverse effects when exposure occurs for a significant portion of
the llfespan [see U.S. EPA (1980b) for a discussion of this concept]. The
RfD 1s route-specific and estimates acceptable exposure for either oral
(RfDg) or Inhalation (RfDj) with the Implicit assumption that exposure
by other routes Is Insignificant.
Composite scores (CSs) for noncardnogens have also been calculated
where data permitted. These values are used for Identifying reportable
quantities and the methodology for their development Is explained In U.S.
EPA (1984).
For compounds for which there Is sufficient evidence of cardnogenlcHy
and RfD values are not derived. For a discussion of risk assessment
methodology for carcinogens refer to U.S. EPA (1980b). Since cancer 1s a
process that Is not characterized by a threshold, any exposure contributes
an Increment of risk. For carcinogens, q^*s have been computed, 1f appro-
priate, based on oral and Inhalation data If available.
1v
-------
ABSTRACT
In order to place the risk assessment evaluation 1n proper context,
refer to the preface of this document. The preface outlines limitations
applicable to all documents of this series as well as the appropriate Inter-
pretation and use of the quantitative estimates presented.
Only one applicable study was found that addressed the toxlcologlcal
consequences of orally administered phenol. From this chronic study an
RfDso of 42 mg/day and an RfDn, of 42 mg/day were estimated based on the
approach suggested by U.S. EPA (1987). This value Is supported by
descriptive chronic and subchronlc studies. These estimates should be
reviewed when adequate chronic data are available.
Inhalation exposure data are more limited. A number of subchronlc
animal studies were located, but all were Inadequate for risk assessment as
discussed 1n the text. An RfDgj and RfDj; were not derived. A CS of 44
was calculated for the effects (death and severe hlstopathologlcal lesions)
observed 1n guinea pigs exposed by Inhalation.
All of these estimates should be reviewed when additional data are
available.
-------
ACKNOWLEDGEMENTS
The Initial draft of this report was prepared by Syracuse Research
Corporation for EPA's Environmental Criteria and Assessment Office,
Cincinnati, OH. Dr. Christopher DeRosa and Karen Blackburn were the
Technical Project Monitors and Helen Ball was the Project Officer. The
final documents In this series were prepared for the Office of Emergency and
Remedial Response, Washington, DC.
Scientists from the following U.S. EPA offices provided review comments
for this document series:
Environmental Criteria and Assessment Office, Cincinnati, OH
Carcinogen Assessment Group
Office of A1r Quality Planning and Standards
Office of Solid Waste
Office of Toxic Substances
Office of Drinking Water
Editorial review for the document series was provided by the following:
Judith Olsen and Erma Durden
Environmental Criteria and Assessment Office
Cincinnati, OH
Technical support services for the document series was provided by the
following:
Bette Zwayer, Pat Daunt, Karen Mann and Jacky Bohanon
Environmental Criteria and Assessment Office
Cincinnati, OH
v1
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TABLE OF CONTENTS
1.
2.
3.
4.
5.
6.
ENVIRONMENTAL CHEMISTRY AND FATE. .
ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS . . .
2.1. ORAL
2.2. INHALATION
TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS
3.1. SUBCHRONIC ,
3.1.1. Oral ,
3.1.2. Inhalation ,
3.2. CHRONIC ,
3.2.1. Oral
3.2.2. Inhalation ,
3.3. TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS
3.3.1. Oral
3.3.2. Inhalation
3.4. TOXICANT INTERACTIONS
CARCINOGENICITY
4.1. HUMAN DATA
4.2. BIOASSAYS
4.2.1. Oral
4.2.2. Inhalation
4.3. OTHER RELEVANT DATA
4.4. WEIGHT OF EVIDENCE
REGULATORY STANDARDS AND CRITERIA
RISK ASSESSMENT
6.1. SUBCHRONIC REFERENCE DOSE (RfDs)
6.1.1. Oral (RfDso)
6.1.2. Inhalation (RfDcr)
Page
1
, , . 3
. . . 3
. . . 3
4
, , 4
. . . 4
4
. . . 8
. . . 8
. . . 10
. . . 10
, . . 10
. . . 11
. . . 11
. . . 12
. . . 12
. . . 12
. . . 12
. . . 13
, . . 13
. . . 13
. . . 15
. . . 16
, . . 16
. . . 16
. . . 16
V11
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TABLE OF CONTENTS (cont.)
Page
6.2. REFERENCE DOSE (RfD) 16
6.2.1. Oral (RfD0) 16
6.2.2. Inhalation (RfDj) 17
6.3. CARCINOGENIC POTENCY (q-\*) 17
7. REFERENCES . 18
APPENDIX: Summary Table for Phenol 25
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LIST OF ABBREVIATIONS
ADI Acceptable dally Intake
CAS Chemical Abstract Service
CS Composite score
OMBA Dimethyl benzanthracene
LOAEL Lowest-observed-adverse-effect level
MED Minimum effective dose
NOAEL No-observed-adverse-effect level
ppm Parts per million
RfD Reference dose
RfDj Inhalation reference dose
RfDg Oral reference dose
RFDgi Subchronlc Inhalation reference dose
RfD$o Subchronlc oral reference dose
RV,j Dose-rating value
RVe Effect-rating value
STEL Short-term exposure limit
TLV Threshold limit value
TWA Time-weighted average
1x
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1. ENVIRONMENTAL CHEMISTRY AND FATE
The relevant physical and chemical properties and environmental fate of
phenol (CAS No. 108-95-2} are summarized below.
Chemical class monocycllc aromatic alcohol
Molecular weight 94.11
Vapor pressure 0.341 mm Hg at 25°C
(Mabey et a!., 1981)
Water solubility 9.3x10* mg/l at 25°C
(Callahan et al.. 1979)
Density 1.072 (Dow Chemical Co., 1976)
Log Kow: 1.46 (Hansch and Leo, 1985)
Log Koc: 16.2-91 (U.S. EPA, 1987)
B1oconcentrat1on factor 2 (Kobayash! et al., 1979)
Half-life 1n
A1r: 7-15 hours (Atkinson, 1985; NLM, 1987)
Water:
-------
The primary removal process for phenol 1n water Is blodegradatlon.
Degradation will be faster In freshwater systems than In estuarlne waters
and faster under aerobic conditions than anaerobic conditions. Photooxlda-
tlon may also be an Important removal mechanism In humlc waters where the
concentration of alkylperoxy radicals 1s significant (NLM, 1987).
In air, phenol 1s expected to react with photochemically generated
hydroxyl radicals. Because of the lack of data on direct photolysis, the
atmospheric half-life reported above Is for reaction with hydroxyl radicals
only. The relatively high water solubility of phenol suggests that signifi-
cant amounts of this compound would also be removed from the atmosphere In
precipitation (NLM, 1987).
0007H -2- 07/24/87
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2. ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS
2.1. ORAL
Delchmann and KepHnger (1981) reported that phenol Is readily absorbed
following oral administration. Humphrey et al. (1980) Investigated the
disappearance of a 40 mg/kg dose of 14C-phenol from the jji s 11u Isolated
small Intestine of Sprague-Dawley rats. Disappearance of radioactivity
appeared to follow first order kinetics with a half-time of 5.5^0.5 minutes
and a rate constant for Intestinal absorption of 0.127*0.003 m1n-1.
2.2. INHALATION
P1otrowsk1 (1971) exposed human volunteers (seven males, one female) to
vapors of phenol through facemasks (6-20 mg/m3) for 8 hours. By measuring
respiratory volume and the concentration of phenol 1n Inspired and expired
air, 1t was estimated that 60-80% of the Inhaled dose was retained through-
out the period of exposure, regardless of the Inspired concentration.
Ohtsujl and Ikeda (1972) found free phenol and conjugated phenol 1n the
urine of workers exposed to 0.0 (7), 0.6 (7), 4.2 (4), -7.8 (8), 8.8 (8), 9.6
(8) and 12.5 mg/m3 (7 subjects) phenol (estimated from air samples).
Levels of total phenols 1n the urine varied proportionally with the levels
of phenol In the atmosphere. The authors compared the amount of phenol
Inhaled/hour with the amount excreted/hour and concluded that phenol 1s
readily absorbed by Inhalation.
0007H -3- 06/20/89
-------
3. TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS
3.1. SUBCHRONIC
3.1.1. Oral. Subchronlc and chronic oral toxIcHy data are summarized In
Table 3-1. In an unpublished study conducted by Dow Chemical Co. (1945,
1976) phenol was administered by gavage (vehicle not specified) to rats at
10, 100 and 200 mg/kg/day 1n 20 dally doses. Slight liver and kidney
effects were reported at the highest dose only. Subsequently, a total of
135 doses of 50 and 100 mg/kg/day phenol was administered by gavage to rats
5 days/week over a 6-month period. At the high dose, slight liver and
moderate kidney damage was observed; at the low dose, only slight kidney
damage was reported. A LOAEL of 50 mg/kg/day (TWA = 35.7 mg/kg/day) was
established on the basis of kidney damage (U.S. EPA, 1988).
A 90-day range finding study was conducted by NCI (1980) to determine
the concentration of phenol to be used 1n F344 rats and B6C3F1 mice for a
2-year cardnogenesls bloassay. The compound was administered 1n drinking
water at five concentrations: 0, 100, 300, 1000, 3000 and 10,000 ppm (0, 19,
57, 190, 570 and 1900 mg/kg bw/day) (Table 3-1). Decreased weight gain
resulting from rejection of water was reported 1n both sexes of both species
at the highest dose level. No other effects were observed.
Two additional subchronlc oral studies were mentioned In U.S. EPA
(1987); however, these studies were available only as English abstracts from
the foreign literature, details were poorly presented and the quality of the
studies was uncertain.
3.1.2. Inhalation. Three subchronlc Inhalation studies reported by NIOSH
(1976) are summarized 1n Table 3-2.
In the subchronlc study by Delchmann et al. (1944), guinea pigs, rats
and rabbits exhibited a wide range of sensitivities to 100 mg/m3 phenol.
0007H -4- 07/21/89
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This dose corresponds to 9.92, 13.27 and 0.44 mg/kg bw/day phenol for guinea
pigs, rats and rabbits, respectively, assuming U.S. EPA (1986) reference
values for animal weight and breathing rate. Of 12 treated guinea pigs, 5
died after only 28 days of exposure. The others had weight loss, signs of
paralysis and numerous pathological changes. In contrast, rats given the
same level of exposure for 74 days had no external or Internal signs of
toxldty. Pathological changes 1n the absence of external signs of toxlclty
were reported for rabbits exposed to phenol at a level of 5.48 mg/kg bw/day.
Rats, mice and monkeys exposed by Inhalation to phenol at levels of
1.44, 2.94 and 1.53 mg/kg bw/day respectively, for 8 hours/day, 5 days/week
for 90 days had no significant adverse toxic effects when compared with
control animals (Sandage, 1961).
In contrast, Mukhltov (1964) observed adverse effects of exposure to
phenol In rats at the 0.009 and 0.409 mg/kg bw/day levels of exposure. In
this study, however, rats were exposed continuously for 61 days, whereas In
the study by Sandage (1961), rats were exposed noncontlnuously for 90 days.
3.2. CHRONIC
3.2.1. Oral. Four studies regarding the chronic toxldty resulting from
oral exposure to phenol were located 1n the available literature and were
summarized In Table 3-1. In the NCI (1980) bloassay (Section 4.2.1.), a
treatment-related Increase In the Incidence of chronic kidney Inflammation
was reported 1n high-dose male and female rats. The Incidences 1n males
were 37/50, 37/50 and 48/52 for the control, low and high doses, respec-
tively. The Incidences 1n females were 7/50, 13/50, and 28/50 for the
control, low and high doses, respectively. Statistical significance was not
reported by the authors, but the Fisher Exact test (U.S. EPA, 1987) revealed
highly significant differences for the Incidence In high-dose males
(p=0.00191) and for the Incidence In high-dose females (p=0.00001).
0007H -8- 07/21/89
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Heller and Pursell (1938) administered phenol In the drinking water of
rats at 0-12,000 ppm (0, 14, 70, 140, 420, 700, 980, 1120, 1400 and 1680
mg/kg bw/day) for 1 year or 2, 3 or 5 generations (see Table 3-1). The lack
of pathological examinations or functional tests 1n this study precludes the
use of these data 1n the calculation of an RfDQ for human Ingestlon of
phenol.
Delchmann and Oesper (1940) administered six concentrations of phenol In
the drinking water of rats for 12 months (see Table 3-1). A decreased
weight gain at the two highest dose levels was the only effect reported.
A teratologlc study of phenol effect was performed In timed-pregnant CD
rats (NTP, 1983). Phenol was administered In distilled water by gavage at
0, 30, 60 and 120 mg/kg/day on gestation days 6-15. Groups of 20-22 females
per dose were weighed, observed for signs of toxlclty and sacrificed on
gestation day 20. No signs of maternal toxlclty or any dose-related
clinical symptoms were observed. There were no significant differences
between treatment groups 1n the number of Implantation sites or In the
number of live fetuses per litter. There was a small but significant
Increase In the number of prelmplantatlon losses between the 30 and 60
mg/kg/day groups and the untreated controls but not for the 120 mg/kg/day
group. However, since Implantation takes place before the first treatment,
which Is to gestation day 6, no relationship between phenol treatment and
the number of Implantation sites could be determined. A detailed terato-
loglc examination, conducted at sacrifice on gestation day 20, revealed a
highly significant reduction In fetal body weight 1n the 120 mg/kg/day
group. A NOAEL without maternal toxlclty was determined to be 60
mg/kg/day. These data were also described by 3ones-Pr1ce et al. (1983a,b)
and are more fully detailed 1n Section 3.3.1.
0007H -9- 07/21/89
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3.2.2. Inhalation. Pertinent data regarding chronic exposure to phenol
by Inhalation could not be located 1n the available literature.
3.3. TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS
3.3.1. Oral. The teratogenldty of phenol was Investigated by Jones-
Price et al. (1983a,b) in both Sprague-Dawley CD rats and CD-I mice.
Phenol, In distilled water (0, 30, 60 or 120 mg/kg/day), was administered by
gavage to timed-pregnant rats (23/group) on gestation days 6-15 (Jones-Price
et al., 1983a). The animals were sacrificed on day 20 of gestation. No
signs of maternal toxlclty were observed. A significant Increase 1n the
proportion of Utters with resorptlon sites was observed at the 30 and 60
mg/kg/day doses, (p<0.05 and p<0.01, respectively), but not at the 120
mg/kg/day level. The number of Implantations was significantly Increased In
the low and medium dose groups, however, and no differences were observed In
the percentage of resorptlons per Utter. The number of live fetuses per
Utter, sex ratio of the Utters, the percentage of affected fetuses per
Utter and the proportion of lifters with dead or malformed fetuses did not
differ among treated groups, but average fetal body weight per litter showed
a significant dose-related (p<0.001) decrease. There was also a significant
(p<0.01) difference between the controls and the high-dose group. No
structural teratogenlc effects resulting from administration of phenol were
reported.
Phenol (0, 70, 140 and 280 mg/kg/day) was administered by gavage In a
concurrent study (Jones-Price et al., 1983b) to timed-pregnant CD-I mice
(31-36/group) on gestation days 6-15. The dams were sacrificed on day 17 of
gestation. Weight loss, tremors, ataxla, lethargy and Irritability were
reported In high-dose dams. Other Indications of maternal toxldty Included
0007H -10- 07/21/89
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Increased mortality 1n the high-dose group (11 vs. 0 In other groups), and
statistically significant dose-related trends for decreased body weight and
gravid uterine weight that were significantly (p<0.01) lower In the
high-dose group compared with the controls. Numbers of Implantation sites
per dam, fetal viability or structural abnormalities of fetuses were not
significantly different among groups. Dose-related decreases (p<0.001 for
trend) 1n mean fetal body weight per Utter were reported; a significantly
lower (p<0.001) body weight was reported 1n the highest dose group compared
with controls. The Incidence of cleft palate was 0/308, 1/290, 1/280 and
8/214 for the 0, 70, 140 and 280 mg/kg/day dose groups, respectively;
however, the differences were not statistically significant. The fetal
effects occurred at doses that also produced maternal toxlclty, and were
probably secondary to the maternal stress. Reproductive effects In rats
associated with Ingestlon of phenol 1n rats were reported 1n the drinking
water study by Heller and Pursell (1938) and are summarized In Table 3-1.
Growth of offspring was retarded at >980 mg/kg bw/day; Impaired mothering
and neonated death occurred at >1120 mg/kg bw/day; offspring dying at birth
occurred at 1400 mg/kg bw/day; and there was no reproduction at 1680 mg/kg
bw/day.
3.3.2. Inhalation. Pertinent data regarding the developmental or
reproductive toxlclty of Inhaled phenol were not located In the available
literature.
3.4. TOXICANT INTERACTIONS
Pertinent data regarding toxicant Interactions between phenol and other
compounds were not located In the available literature; however, Chains
(1973) reported that phenol and nitrites could react to form p-nltrosophenol
under 1n vitro conditions.
0007H -11- 07/21/89
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4. CARCINOGENICITY
4.1. HUMAN DATA
Data pertaining to the cardnogenldty of phenol 1n humans were not
located 1n the available literature.
4.2. BIOASSAYS
4.2.1. Oral. An NCI (1980) bloassay of phenol was conducted to test F344
rats and B6C3F1 mice for possible cardnogenldty. Phenol was administered
1n the drinking water to groups of 50 male and 50 female rats and 50 male
and 50 female mice at concentrations of 0, 2500 and 5000 ppm for 103 weeks.
A dose-related decrease 1n weight gain was reported 1n treated animals,
which was attributed to decreased water consumption. No other clinical
signs were observed. Survival was comparable among control and treated
groups. Statistically significant Increased Incidences of leukemlas or
lymphomas were reported In low-dose male rats compared with controls. The
Incidences 1n high-dose males were also higher but were not significantly
different from matched controls. In low-dose male rats, the Incidence of
Interstitial cell tumors of the testls was Increased when compared with
controls. Low-dose male rats also had a significant Incidence of C-cell
carcinomas In the thyroid and pheochromocytomas In the adrenals. No
Increased Incidences of tumors were reported 1n female rats or 1n female or
male mice. Based on the high spontaneous tumor rate observed In matched
controls and the lack of a positive effect In the high-dose groups the
association between phenol and cancer Is not clearly established. NCI
(1980) concludes that phenol Is not carcinogenic under conditions of this
bloassay. It was suggested by the reviewers, however, that phenol be
considered for retestlng because of the equivocal results obtained In male
rats.
0007H -12- 06/20/89
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4.2.2. Inhalation. Data pertaining to the cardnogenlclty of Inhaled
phenol In animals were not located In the available literature.
4.3. OTHER RELEVANT DATA
Phenol was reported to be mutagenlc to Escherlchla coll, but only at
concentrations of phenol (0.1-0.2%) that caused a reduction In survival
(0.5-1.7% survival) (Demerec et al., 1951). In an \i± vitro experiment,
phenol Induced mutation In gonads of Drosophlla (Hadorn and Nlggll, 1946).
Dickey et al. (1949) reported that phenol was not mutagenlc to Neurospora.
Negative results were reported with and without S-9 In an assay using
hlstldlne auxotrophs of Salmonella typhlmurlum (Pool and Lin, 1982).
Haworth et al. (1983) and Florin et al. (1980) reported that phenol did not
exhibit mutagenlc activity In similar tests using the same strains of £.
typhlmurlum that were used by Pool and L1n (1982). Gocke et al. (1981),
however, reported mutagenlc activity In one strain of S. typhlmurlum with
S-9, which was evaluated by the above Investigators with negative results.
Boutwell and Bosch (1959) Investigated the tumor-promoting ability of
phenol In skin painting experiments with several strains of mice and using
DMBA as an Initiator. Phenol appeared to be a weak complete carcinogen In
these studies. Phenol apparently Initiated and promoted the development of
skin papHlomas and carcinomas, particularly 1n a strain of mice selected
for sensitivity to DMBA Initiation and croton oil promotion. Similar
results were obtained by Salaman and Glendennlng (1957) 1n strain "S" mice.
4.4. WEIGHT OF EVIDENCE
IARC has not evaluated the risk to humans associated with oral or Inha-
lation exposure to phenol. Phenol was administered In the drinking water of
mice and rats for 2 years at levels of 2500 and 5000 ppm (NCI, 1980).
0007H -13- 06/20/89
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Statistically significant Increased Incidences of pheochromocytomas of the
adrenal medulla, C-cell carcinoma of the thyroid and leukemlas or lymphomas
were reported 1n male rats at 2500 ppm but not at 5000 ppm. No Increased
tumor Incidences were observed 1n female rats or female and male mice. NCI
(1980) concluded that phenol was not carcinogenic under the conditions of
the bloassay and It was suggested that phenol be considered for retestlng.
Applying the U.S. EPA (1986) criteria for overall weight of evidence of
cardnogenlclty to humans, data are Inadequate and the chemical is most
appropriately designated a Group D - Not Classified chemical. This Is
consistent with the analysis by U.S. EPA (1987).
0007H -H- 07/21/89
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5. REGULATORY STANDARDS AND CRITERIA
Based on subchronlc animal studies (Delchmann et al., 1944), the
American Conference of Governmental Industrial Hyglenlsts established a
TWA-TLV of 5 ppm (19 mg/m3) and a STEL of 10 ppm (38 mg/m3) (ACGIH,
1986a,b). NIOSH (1976) recommended a TWA-TLV for a 10-hour workday, 40-hour
week of 20 mg/m3, and a 60 mg/m3 celling for a period of exposure not to
exceed 15 minutes. The OSHA (1985) occupational permissible exposure limit
for phenol 1s also 5 ppm (19 mg/m3). The Public Health Service drinking
water standard for phenols Is 1.0 vg/l (U.S. DHEW, 1962).
Based on the subchronlc study by Dow Chemical Co. (1976) and using a
safety factor of 500, the U.S. EPA (1980a) calculated an Interim ADI of 0.1
mg/kg/day or 7.0 mg/man/day for Ingestlon of phenol. From this Interim ADI,
and assuming that 2.0 I water/day and 0.0065 kg fish/day (with a bio-
concentration factor of 2.0) are consumed by the reference 70 kg man, an
Interim ADI for drinking water of 3.5 mg/l was calculated. Since an
organoleptlc threshold (taste) of 0.3 mg/l was reported, however, a
criterion level for phenol 1n water of 0.3 mg/l was established.
0007H -15- 07/21/89
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6. RISK ASSESSMENT
6.1. SUBCHRONIC REFERENCE DOSE (RfD$)
6.1.1. Oral (RfDso). Based on the rat study by NTP (1983), a NOAEL of
60 mg/kg/day was established (see Section 3.1.1.) for reduced fetal body
weight. U.S. EPA (1988) verified a chronic RfO based upon this same study
because the exposure was considered to be chronic for the fetus. They chose
a composite uncertainty factor (UF) of 100 (10 for Intraspecles, 10 for
Interspecles). Medium confidence Is placed 1n this RfDSQ. Analysis of
the data regarding the oral toxldty of phenol 1s expanded In Section 6.2.1.
6.1.2. Inhalation (RfDSI). As discussed 1n Section 3.1.2., the
available subchronlc data are not suitable for use 1n quantitative risk
assessment.
U.S. EPA (1987) calculated a CS for the effects (death, severe signs of
toxldty and extensive hlstopathologlcal changes) observed 1n guinea pigs
exposed to atmospheric phenol at 100 mg/m3 7 hours/day, 5 days/week for a
total of 29 exposures (Delchmann et al., 1944). The resulting exposure
corresponded to 4.96 mg/kg/day. A chronic human MED of 5.6 mg/day was
calculated, which Is equivalent to an RV. of 4.4. An RV of 10 was
chosen to represent mortality, the most severe effect. A CS of 44, the
product of RV. and RV , results In an RQ of 10. The complete derivation
of this value 1s presented In U.S. EPA (1987).
6.2. REFERENCE DOSE (RfO)
6.2.1. Oral (RfDQ). As discussed In Section 3.2.1. and summarized In
Table 3-1, four chronic oral studies were located In the literature. Data
from both the Heller and Pursell (1938) and Delchmann and Oesper (1940)
studies presented no pathological or functional evaluation and therefore are
0007H -16- 07/21/89
-------
unsuitable for use In risk assessment. Based on a verified analysis
presented by the U.S. EPA (1987b), the LOAEL of 50 mg/kg/day from the Dow
Chemical Co. (1945) study was used as a basis for a chronic oral RfD.
Further review Indicated that a teratologlc study using rats would be
preferable because the exposure was considered to be chronic for the fetus.
The LOAEL for reduced fetal body weight was determined to be 120 mg/kg/day
and the NOAEL was 60 mg/kg/day. Applying an uncertainty factor of 100
results In an RfOQ of 0.6 mg/kg/day or 42 mg/day for a 70 kg man (U.S.
EPA, 1988). Confidence In this value was rated medium.
6.2.2. Inhalation (RfD,). Data pertaining to the chronic toxlclty of
Inhaled phenol were not located 1n the available literature, and, as
discussed In Section 3.1.2., the available subchronlc data are not suitable
for use 1n quantitative risk assessment. An RfD,, therefore, Is not
calculated.
6.3. CARCINOGENIC POTENCY (q^)
The lack of pertinent data regarding the carc1nogen1c1ty of phenol
precludes the assessment of carcinogenic risk.
0007H -17- 07/21/89
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7. REFERENCES
ACGIH (American Conference of Governmental Industrial Hyg1en1sts). 1986a.
Threshold Limit Values for Chemical Substances and Physical Agents In the
Workroom Environment with Intended Changes for 1986-1987. Cincinnati, OH.
p. 26.
ACGIH (American Conference of Governmental Industrial Hyglenlsts). 1986b.
Documentation of the Threshold Limit Values and Biological Exposure Indices,
5th ed. Cincinnati, OH. p. 469-471.
Atkinson, R. 1985. Kinetics and mechanisms of the gas phase reactions of
the hydroxyl radical with organic compounds under atmospheric conditions.
Chem. Rev. 85: 69-201.
Baker, M.D. and C.I. Mayfleld. 1980. M1crob1al and non-biological decompo-
sition of chlorophenols and phenols 1n soil. Water A1r Soil Pollut. 13:
411-424.
Boutwell, R.K. and K.O. Bosch. 1959. The tumor-promoting action of phenol
and related compounds for mouse skin. Cancer Res. 19: 413-424. (Cited In
U.S. EPA, 1987)
Callahan, M.A., M.W. Sllmak, N.W. Gabel, et al. 1979. Water-Related
Environmental Fate of 129 Priority Pollutants. Vol. II. Office of Water
Planning and Standards, Office of Water and Waste Management, U.S. EPA,
Washington, DC. EPA 440/4-79-029b.
0007H -18- 07/21/89
-------
Chains, B.C. 1973. Rapid nltrosatlon of phenols and Us Implications for
health hazards from dietary nitrites. Nature. 244: 466.
Delchmann, W.B. and M.L. Kepllnger. 1981. Industrial toxicology. Phenols
and phenolic compounds. Iin: Patty's Industrial Hygiene and Toxicology, 3rd
rev. ed., Vol. 2A, G.O. Clayton and F.E. Clayton, Ed. John Wiley and Sons,
Inc., NY. p. 2567-2676.
Delchmann, W. and P. Oesper. 1940. Ingestlon of phenol -- Effects on the
albino rat. Ind. Med. 9: 296. (Cited In U.S. EPA, 1987)
Delchmann, W.B., K.V. Kltzmlller and B.S. WHherup. 1944. Phenol studies.
VII. Chronic phenol poisoning, with special reference to the effects upon
experimental animals of the Inhalation of phenol vapor. Am. 0. Clln.
Pathol. 14: 273-277. (Cited 1n NIOSH, 1976)
Delflno, 0.0. and D.O. Dube. 1976. Persistent contamination of groundwater
by phenol. 0. Environ. Scl. Health. All: 345-355.
Demerec, M., et al. 1951. A survey of chemicals for mutagenlc action on £.
coll. Am. Natur. 85: 119. (Cited In U.S. EPA, 1980a)
Dickey, F.H., G.H. Cleland and C. Lotz. 1949. The role of organic
peroxides In the Induction of mutations. Proc. Natl. Acad. Scl. 35:
581-586. (Cited In U.S. EPA, 1980a)
0007H -19- 07/21/89
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Dow Chemical Co. 1945. The toxldty of phenol. Blochem. Res. Lab.
(Unpublished report by E.M. Adams, 4/12/45). (CHed In U.S. EPA, 1987)
Dow Chemical Co. 1976. References and literature review pertaining to
toxlcologlcal properties of phenol. Toxlcol. Res. Lab. (Unpubl. manu-
script) (Cited 1n U.S. EPA, 1980a)
Ehrllch, G.G., D.F. Goerhltz, E.M. Godsy and M.F. Hult. 1982. Degradation
of phenolic contaminants In groundwater by anaerobic bacteria: St. Louis
Park, Minnesota. Groundwater. 20: 703-710.
Florin, I., L. Rutberg, M. Curvall and C.R. Enzell. 1980. Screening of
tobacco smoke constituents for mutagenlclty using the Ames test.
Toxicology. 15(3): 219-232. (CUed In U.S. EPA, 1987)
Gocke, E., M.T. King, K. Eckhardt and D. Wild. 1981. Mutagenlclty of
cosmetics Ingredients licensed by the European communities. Mutat. Res.
90(2): 91-109. (CHed In U.S. EPA, 1987)
Hadorn, E. and H. Nlggll. 1946. Mutations 1n Drosophlla after chemical
treatment of gonads l£ vitro. Nature. 157: 162-163.
Hansch, C. and A.J. Leo. 1985. Medchem Project. Issue no. 26. Pomona
College. Claremont, CA.
Haworth, S., T. Lawler, K. Mortelmans, W. Speck and B. Zelger. 1983.
Salmonella mutagenlclty test results for 250 chemicals. Environ. Mutagen.
Suppl. 1: 3-142. (Cited In U.S. EPA, 1987)
0007H -20- 07/21/89
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Heller, V.G. and L. Purse!!. 1938. Phenol-contaminated waters and their
physiological action. J. Pharmacol. Exp. Ther. 63: 99-107. (CHed 1fi
NIOSH, 1976)
Humphrey, M.3., C.W. Filer, D.J. Jeffery, P.P. Langley and G.A. Wadds.
1980. The availability of carfecllUn and Us phenol moiety In rat and dog.
Xenoblotlca. 10(10): 771-778. (CHed In U.S. EPA, 1987)
Jones-Price, C., T.A. Ledoux, F.R. Reel, P.M. Fisher and L. Langhoff-Paschke.
1983a. Teratologlc evaluation of phenol (CAS No. 108-95-2) 1n CD rats.
NTIS PB83-247726, 120 p. Gov. Rep. Announce. Index (U.S.) 1983. 83(25):
6247.
Jones-Price, C., T.A. Ledoux, J.R. Reel, L. Langhoff-Paschke, M.C. Maur and
C.A. Klmmel. 1983b. Teratologlc evaluation of phenol (CAS No. 108-95-2) in
CD-I mice. September 18, 1980 to January 12, 1981. ~NTIS PB85-104451, 99 p.
Kobayashl. K., H. Akltake and K. Manabe. 1979. Relation between toxlclty
and accumulation of various chlorophenols In goldfish. Bull. Jap. Soc. Scl.
Fish. 45: 173-175.
Mabey, W.R., J.H. Smith, R.T. Podoll, et al. 1981. Aquatic Fate Process
Data for Organic Priority Pollutants. Monitoring and Data Support Dlv.,
Office of Water Regulations and Standards, U.S. EPA, Washington, DC. EPA
440/4_81-014.
0007H -21- 07/21/89
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MukhHov, B. 1964. The effect of low phenol concentrations of the organism
of man or animals and their hygienic evaluation, in: USSR Literature on AVr
Pollution and Related Occupational Diseases A Survey, Vol. 9, B.S.
Levlne, Trans. U.S. Dept. of Commerce, p. 185-199. NTIS 64-11574. (Cited
1n NIOSH, 1976)
NCI (National Cancer Institute). 1980. Carclnogenesls Testing Program.
Bloassay of phenol for possible carc1nogen1c1ty. Report, NCI-CG-TR-203,
DHHS/PUB/NIH80-1759, NTP-80-15; NTIS PB80-217946, 119 p. Gov. Rep.
Announce. Index (U.S.) 1980, 80(25), 5298.
NIOSH (National Institute for Occupational Safety and Health). 1976.
Criteria for a Recommended Standard...Occupational Exposure to Phenol. U.S.
DHEW, PHS, CDC, Rockvllle, MD.
NLM (National Library of Medicine). 1987. Hazardous Substance Data Base.
Report No. 113. Online.
NTP (National Toxicology Program). 1983. Teratologlc evaluation of phenol
1n CD rats and mice. Report prepared by Research Triangle Institute,
Research Triangle Park, NC. NTIS PB83-247726. Gov. Rep. Announce. Index.
83(25): 6247.
Ohtsujl, H. and M. Ikeda. 1972. Quantitative relationship between
atmospheric phenol vapour and phenol In the urine of employees 1n Bake!He
factories. Br. J. Ind. Med. 29: 70-73. (CUed In NIOSH, 1976)
0007H -22- 07/21/89
-------
OSHA (Occupational Safety and Health Administration). 1985. OSHA Occu-
pational Standards - Permissible Exposure Limits. Code of Federal Regula-
tions. 29 CFR 1910.1000.
Plotrowskl, O.K. 1971. Evaluation of exposure to phenol. Absorption of
phenol vapour In the lungs and through the skin and excretion of phenol In
urine. Br. J. Ind. Med. 28: 172-178.
Pool, B.L. and P.Z. L1n. 1982. Mutagenlclty testing In the Salmonella
typhlmurlum assay of phenolic compounds and phenolic fractions obtained from
smokehouse condensates. Food Chem. Toxlcol. 20(4): 383-391. (Cited In
U.S. EPA, 1987a)
Salaman, M.H. and O.M. Glendennlng. 1957. Tumor promotion In mouse skin by
scleroslng agents. Br. J. Can. 11: 434-444. (Cited 1n U.S. EPA, 1987)
Sandage, C. 1961. Tolerance criteria for continuous Inhalation exposure to
toxic material. ASO Technical Report 61-519 (I). Midwest Research
Institute, Kansas City, MO. p. 1-29. (CHed 1n NIOSH, 1976)
U.S. DHEW (Department of Health, Education and Welfare). 1962. Public
Health Service Drinking Water Standards. Consumer Protection and Environ-
mental Health Service, Environmental Control Administration, Rockville, MD.
p. 51.
0007H -23- 07/21/89
-------
U.S. EPA. 1980a. Ambient Water QualHy Criteria for Phenol. Prepared by
the Office of Health and Environmental Assessment, Environmental Criteria
and Assessment Office, Cincinnati, OH for the Office of Water Regulations
and Standards, Washington, DC. EPA-440/5-80-066. NTIS PB81-117772.
U.S. EPA. 1980b. Guidelines and Methodology Used In the Preparation of
Health Effects Assessment Chapters of the Consent Decree Water QualHy
Criteria. Federal Register. 45(231): 79347-79357.
U.S. EPA. 1984. Methodology and Guidelines for Ranking Chemicals Based on
Chronic Tox1c1ty Data. Prepared by the Office of Health and Environmental
Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH for
the Office of Emergency and Remedial Response, Washington, DC.
U.S. EPA. 1986. Guidelines for Carcinogen Risk Assessment. Federal
Register. 51(185): 33992-34003.
U.S. EPA. 1987. Health and Environmental Effects Profile for Phenol.
Prepared by the Office of Health and Environmental Assessment, Environmental
Criteria and Assessment Office, Cincinnati, OH for the Office of Solid Waste
and Emergency Response, Washington, DC. EPA/600/X-87/121. NTIS PB89-
132112/AS.
U.S. EPA. 1988. Integrated Risk Information System (IRIS). Reference dose
(RfD) for oral exposure for phenol. Online. (Verification date 11/16/88.)
Office of Health and Environmental Assessment, Environmental Criteria and
Assessment Office, Cincinnati, OH.
0007H -24- 08/14/89
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