820K87013
March 31, 1987
ETHYLBENZENE
Health Advisory
Office of Drinking Water
U.S. Environmental Protection Agency
I. INTRODUCTION
The Health Advisory (HA) Program, sponsored by the Office of Drinking
Water (ODW), provides information on the health effects, analytical method-
ology and treatment technology that would be useful in dealing with the
contamination of drinking water. Health Advisories describe nonregulatory
concentrations of drinking water contaminants at which adverse health effects
would not be anticipated to occur over specific exposure durations. Health
Advisories contain a margin of safety to protect sensitive members of the
population.
Health Advisories serve as informal technical guidance to assist Federal,
State and local officials responsible for protecting public health when
emergency spills or contamination situations occur. They are not to be
construed as legally enforceable Federal standards. The HAs are subject to
change as new information becomes available.
Health Advisories are developed for One-day, Ten-day, Longer-term
(approximately 7 years, or 10% of an individual's lifetime) and Lifetime
exposures based on data describing noncarcinogenic end points of toxicity.
Health Advisories do not quantitatively incorporate any potential carcinogenic
risk from such exposure. For those substances that are known or probable
human carcinogens, according to the Agency classification scheme (Group A or
B), Lifetime HAs are not recommended. The chemical concentration valuas for
Group A or B carcinogens are correlated with carcinogenic risk estimates by
employing a cancer potency (unit risk) value together with assumptions for
lifetime exposure and the consumption of drinking water. The cancer anit
risk is usually derived from the linear multistage model with 95% upper
confidence limits. This provides a low-dose estimate of cancer risk to
hunans that is considered unlikely to pose a carcinogenic risk in excess
of the stated values. Excess cancer risk estimates may also be calculated
using the One-hit, Weibull, Logit or Probit models. There is no current
understanding of the biological mechanisms involved in cancer to suggest that
any one of these models is able to predict risk more accurately than another.
Because each model is based on differing assumptions, the estimates tnat are
derived can differ by several orders of magnitude.
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This Health Advisory is based on information presented in the Office of
Drinking Water's Health Effects Criteria Document (CD) for Sthylbenzene (U.S.
EPA, 1985a). The HA and CD formats are similar for easy reference. Individuals
desiring further information on the toxicological data base or rationale for
risk characterization should consult the CD. The CD is available for review
at each EPA Regional Office of Drinking Water counterpart (e.g., Water Supply
Branch or Drinking Water Branch), or for a fee from the National Technical
Information Service, U.S. Department of Commerce, 5235 Port Royal Rd.,
Springfield, VA 22161, PB # 86-117835/AS. The toll-free number is (800)
336-4700; in the Washington, D.C. area: (703) 487-4650.
II. GENERAL INFORMATION AND PROPERTIES (Verschueren, 1983; Amoore and Hautala, 1983)
Chemical Name Ethylbenzene
Cas No. 100-41-4
Chemical Structure
Synonyms
Phenyl ethane, ethylbenzol, EB
Uses
Styrene manufacture
Acetophenone manufacture
Solvent
Asphalt constituent
Naptha constituent
Properties
Chemical Formula C8H1 0
Molecular Weight 106.18
Physical State (25°C) Colorless liquid
Boiling Point 136.2°C
Melting Point -94.97°C
Density
Vapor Pressure 7 mm at 20°C
Water Solubility 152 mg/L (at 20°C)
Log Octanol/Water Partition 3.15
Coefficient
Taste Threshold (water) 0.029 mg/L
Odor Threshold (water) 0.029 mg/L
Odor Threshold (air) 0.062 mg/L
Conversion Factor —
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Occurrence
Ethylbenzene, a clear, flammable liquid found in gasoline, is produced
commercially by the alkylation of benzene with ethylene. In 1982,
the U.S. production of ethylbenzene totaled 3.3 million tons.
Very little information is available on the occurrence of ethylbenzene
in 12,000 drinking water supplies in the U.S. drawing water from
surface rivers and streams. However, the testing of 945 ground water
supplies has revealed that approximately 0.6 % contain ethylbenzene.
The median concentration detected in "non random" segment of the
study was 0.87 ug/L (Westrick et al., 1983).
III. PHARMACOKINETICS
Absorption
Data regarding the absorption of ethylbenzene from the gastrointestinal
tract of humans following oral ingestion could not be located.
Since approximately 90% of an oral dose of ethylbenzene (1.78 g/rabbit)
is excreted as metabolites (SI Masry et al., 1956), the chemical is
readily absorbed in rabbits.
For human volunteers exposed by inhalation to ethylbenzene for 8 hours
at 100, 187, 200 or 370 mg/m-^, the average percent of vapor absorbed
(measured spectrophotometrically) through the respiratory tract was
64% (Bardodej and Bardodejova, 1970).
Absorption of an aqueous solution of ethylbenzene through human hand skin
(109.3 to 113.9 mg/L for 1 to 2 hours) was equivalent to 118 ug/cm2/hour
(Dutkiewicz and Tyras, 1967).
Distribution
Following a 6-hour inhalation exposure at 1 mg/m3, absorbed ethylbenzene
is distributed throughout the body in rats. However, the highest
levels were detected in the kidney, lung, adipose tissue, digestive
tract and liver (Chin et al., 1980).
Metabolism
After inhalation exposure, ethylbenzene undergoes rapid metabolism
in humans, primarily to form mandelic acid and phenylglyoxylic acid.
These two metabolites accounted for 64% and 25%, respectively, of the
absorbed dose in humans (Bardodej and Bardodejova, 1970). Formation
of minor metabolites including methylphenyl carbinol and 2-ethylphenol
accounted for approximately 5% and 1%, respectively, in humans (Bardodej
and Bardodejova, 1970; Angerer and Lehnert, 1979).
The major metabolites formed in humans and rats are not the same.
Mandelic acid and phenylglyoxylic acid constitute 64 and 25% of the
metabolites in humans (Bardodej and Bardodejova, 1970), while in
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rats, 1-phenylethanol (25%), benzole acid (27%) and mandelic acid
(25%) are the main metabolites (Engstrom, 1985).
Excretion
Urinary excretion of metabolites by rabbits was reported to be
complete within 24 hours after oral dosing with 1.78 grams/rabbit
(El Masry et al., 1956).
In humans, most of the inhaled dose was eliminated in the urine
within 24 hours after exposure was terminated (Engstrom and Bjarstrom,
1978; Hagemann and Angerer, 1979).
IV. HEALTH EFFECTS
Humans
0 In experiments with human volunteers, an 8-hour inhalation exposure
to ethylbenzene at a concentration of 100 ppm (435 mg/m3) did not
result in adverse health effects (Bardodej and Bardodejova, 1970).
Increasing this level (increase not specified) resulted in sleepiness,
fatigue, headache and mild eye and respiratory irritation.
Animals
Short-term Exposure
0 Estimated acute LD^Q values of 3.5 g/kg to 5.46 g/kg were reported in
rats (Wolf et al., 1956; Smyth et al., 1962).
0 An acute dermal LD50 value of 17.8 ml/kg (approximately 15,400 nig/kg)
was reported in rabbits (Smyth et al., 1962).
0 An inhalation exposure of 4,000 ppm (approximately 17,400 rtig/Ti3) for
four hours was lethal to 3 of 6 rats (Smyth et al., 1962).
0 During LD50 studies systemic toxic effects were observed predominantly
in the liver and kidney (Wolf et al., 1956) and central nervous system
(Faustov, 1958).
0 Other acute effects include irritation of the conjunctiva (Wolf et al.,
1956) and slight necrosis of the cornea (Smyth et al., 1962).
Long-term Exposure
0 Liver and kidney effects were observed in rats (10 females/dose)
exposed orally to ethylbenzene in olive oil for six months (Wolf
et al., 1956). Doses of 408 and 680 mg/kg/day caused increases in
liver and kidney weights, and cloudiness and swelling of hepatocytes
and renal tubular epithelium. No effects were observed in rats
exposed to 13.6 and 136 mg/kg/day.
0 No chronic exposure studies were identified in the available literature.
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Reproductive Effects
0 No studies on the effects of ethylbenzene on reproduction were located
in the available literature.
Developmental Effects
0 Ethylbenzene did not elicit embryotoxicity, fetotoxicity or terato-
genicity in inhalation studies at concentrations up to 1,000 ppm
(4,348 mg/ra3) in rats and rabbits for 6 to 7 hours/day on days 1 to
19 and 1 to 24 of gestation, respectively (Hardin et al., 1981).
0 Female rats exposed at 1,000 ppm had increased liver, kidney and
spleen weights suggestive of maternal toxicity. There was no maternal
toxicity observed when the rats were exposed to 100 ppm of ethylbenzene.
{Hardin et al., 1981).
Mutagenicity
0 No mutagenic activity was detected in S_._ typhimurium strains TA98,
TA100, TA1535, TA1537 following ethylbenzene exposure both with and
without metabolic activation in plate assays at concentrations up to
3 mg/plate (Florin et al., 1980; Nestmann et al., 1980).
0 Dean et al. (1985) reported that ethylbenzene (0.2 to 2,000 ug/plate)
did not induce mutations in bacteria, gene conversion in yeast or
chromosome damage in rat liver (RL4) epithelial cells.
0 In the Drosophila recessive lethal test, ethylbenzene did not increase
the frequency of recessive lethals (Donner et al., 1979).
Carcinogenicity
0 Pertinent data on the carcinogenic potential of ethylbenzene were not
identified in the available literature. An NCI bioassay is in the
planning stage.
V. QUANTIFICATION OF TOXICOLOGICAL EFFECTS
Health Advisories (HAs) are generally determined for One-day, Ten-day,
Longer-term (approximately 7 years) and Lifetime exposures if adequate data
are available that identify a sensitive noncarcinogenic end point of toxicity.
The HAs for noncarcinogenic toxicants are derived using the following formula:
HA = (NOAEL or LOAEL) x (BW) = /L ( /L}
(UF) x ( L/day)
where:
NOAEL or LOAEL = No- or Lowest-Observed-Adverse-Effect-Level
in mgAg bw/day.
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BW = assumed body weight of a. child (10 kg) or
an adult (70 kg).
UF = uncertainty factor (10, 100 or 1,000), in
accordance with NAS/ODW guidelines.
L/day = assumed daily water consumption of a child
(1 L/day) or an adult (2 L/day).
One-day Health Advisory
No adequate dose-response data exist using the oral route of exposure
from which to calculate a One-day Health Advisory. Therefore, the derivation
of the one-day level is based upon a 100 ppm (435 mg/m3) NOAEL identified in
18 human male volunteers following a single 8-hour inhalation exposure as
conducted by Bardodej and Bardodejova (1970). An inhalation absorption
efficiency of 64% is used, based on data from that study (Bardodej and
Bariodejova, 1970).
The total absorbed dose and the One-day HA for a 10 kg child are
calculated as follows:
Step 1: Determination of Total Absorbed Dose (TAD)
TAD = (435 mg/m3) (8 m3/day) (0.64) = 3UQ mg/kg/day
Step 2: Determination of One-day HA
One-day HA = (_31 .8 mg/kg/day) (10 kg) = 32 mg/L (32000 ug/L)
(10) (1 L/day)
where:
435 mg/m3 = NOAEL based on absence of effects in humans following
inhalation exposure.
8 m3/day = assumed volume of air inhaled per daily 8-hour exposure.
0.64 = absorption efficiency reported by Bardodej and Bardodejova
(1970).
70 kg = assumed body weight of an adult.
10 kg = assumed body weight of a child.
2 L/day = assumed daily water consumption of an adult.
1 L/day = assumed daily water consumption of a child.
10 = uncertainty factor, chosen in accordance with NAS/ODW
guidelines for use with a NOAEL from a human study.
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Ten-day Health Advisory
Because of the lack of appropriate exposure duration data, the ten-day
HA will be calculated from the One-day HA. The One-day HA will be divided by
10 to give estimated Ten-day HA values. The resulting Ten-day HA for a child
is as follows:
Ten-day HA = 32 m
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Step 1: Determination of the Reference Dose (RfD)
RfD = (136 mg/kg/day) (5 ) ,= 0>097 mg/kg/day
(1,000) (7)
where:
136 mg/kg/day = NOAEL for absence of renal and hepatic effects in
rats exposed for 130 days.
5/7 = conversion of 5 days/week dosing regimen to continuous
7 days/week exposure pattern.
1,000 = uncertainty factor, chosen in accordance with NAS/ODW
guidelines for use with a NOAEL from an animal study
of less-than-lifetime duration.
Step 2: Determination of the Drinking Water Equivalent Level (DWEL)
DWEL = (0.097 mg/kg/day)(70 kg) = 3.4 mg/L (3,400 ug/L)
(2 L/day)
where:
0.097 mgA9/<3ay = RfD.
70 kg = assumed body weight of an adult.
2 L/day = assumed daily water consumption of an adult.
Step 3: Determination of the Lifetime Health Advisory
Lifetime HA = (3.4 mg/L) (20%) =0.68 mg/L
where:
3.4 mg/L = DWEL.
20% = assumed relative source contribution from water.
Evaluation of Carcinogenic Potential
0 Because of the lack of data, an assessment of the carcinogenic risk
of ethylbenzene is not possible at this time.
° The International Agency for Research on Cancer has not classified
ethylbenzene in any of its categories of carcinogenic potential.
0 Applying the criteria described in EPA's guidelines for assessment
of carcinogen .risk (U.S. EPA, 1986), ethylbenzene is classified in
Group D: not classified. This category is for agents with inadequate
animal evidence of carcinogenicity.
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VI. OTHER CRITERIA, GUIDANCE AND STANDARDS
0 The American Conference of Government Industrial Hygienists has
recommended an occupational standard (TWA) in air and TLV of 100 ppm
(435 mg/m3; ACGIH, 1980).
0 EPA/ODW has proposed a RMCL of 0.68 mg/L (U.S. EPA, 1985e).
VII. ANALYTICAL METHODS
0 Analysis of ethylbenzene is by a purge-and-trap gas chromatographic
procedure used for the determination of volatile aromatic organic
compounds in water (U.S. EPA, 1985b). This method calls for the
bubbling of an inert gas through the sample and trapping ethylbenzene
on an adsorbant material. The adsorbant material is heated to drive
off ethylbenzene onto a gas chromatographic column. The gas chromato-
graph is temperature programmed to separate the method analytas which
are then detected by the photoionization detector. This method is
applicable to the measurement of ethylbenzene over a concentration
range of 0.02 to 1500 ug/L. Confirmatory analysis for benzene is by
mass spectrometry (U.S. EPA, 1985c). The detection limit for
confirmation by mass spectrometry is 0.2 ug/L.
VIII. TREATMENT TECHNOLOGIES
0 Aeration appears to offer the best potential for removing ethylbenzene
from contaminated water. Ethylbenzene has a high Henry's Law Constant
of 35 atm (U.S. EPA, 1985d).
0 In an actual packed aeration column (PAC) pilot testing program,
ethylbenzene removal efficiencies ranged from 71.8 to >99.8% (U.S.
EPA, 1985d). The column used had a one foot diameter and was packed
with Tripack packing material (#2). Influent concentrations of
ethylbenzene ranged from <1 to 200 ug/L. Air-to-water ratios varied
from 10:1 to 126:1. Liquid loading rates varied from 12.7 to 50.9
gpm/ft2. Ambient water temperature was 70°F. Removal efficiencies
were >90% for all test runs but one. In this single exception, an
efficiency of 71.8% was obtained. In this test run the ethylbenzene
concentration was high (200 ppb) and the air-to-water ratio low -
10:1 (U.S. EPA, 1985d).
0 A field test of PAC also was conducted on water contaminated by a
gasoline spill (Cummins, 1985). Several benzene derivatives including
ethylbenzene were found in this water. The aeration column was
7.3 x 0.6 m and was packed to 5.5 m with 1 inch plastic saddles.
Air-to-water ratios of from 8:1 to 88:1 were used. Ethylbenzene
was decreased to below detection (<0.5 ug/L) whenever the air-to-water
ratios were 20:1 or greater. Ethylbenzene was detected if lower
air-to-water ratios were used. A total of 75 samples were tested.
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0 Decarbonators, which can be considered as modified aerators, were used
to remove synthetic organic contaminants including ethylbenzene at Water
Factory 21 (U.S. EPA, 1985d). The air-to-water ratio was 22:1. Levels
of influent ethylbenzene contamination were 0.067 and 0.23 ug/L. The
decarbonators removed 39.8 and 56.51% of the ethylbenzene, respectively.
0 Granular activated carbon (GAG) also is at least partially effective
in the removal of ethylbenzene from solution by adsorption. Over two
separate trial periods, GAC was found to remove some of the ethylbenzene
from contaminated drinking water. At an influent concentration of
0.06 ug/L, 45% of the ethylbenzene was removed. When the influent
was 0.07 ug/L, 17% was removed (McCarty et al., 1979).
0 Application of PAC for ethylbenzene removal was tested at the Sunny
Isles Water Treatment Plant (Florida) (U.S. EPA, 1985d). For a
14-month period, 7.1 mg/L PAC was added to the water at the wellfield.
For 3 of 5 samples analyzed, >99% of the ethylbenzene was removed;
for 2 samples, the removal rate was only 33%.
0 In one study, conventional treatment was found to reduce the ethyl-
benzene in water containing 0.7 ug/L by 43% (U.S. EPA, 1985d).
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Angerer, J., and G. Lehnert. 1979. Occupational chronic exposure to solvents.
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Chin, B.H., J.A. McKelvey, T.R. Tyler, L.J. Calisti, S.J. Kozbelt and L.J.
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Dean, B.J., T.M. Brooks, G. Hodson-Walker and D.H. Hutson. 1985. Genetic
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Donner, M., J. Maki-Paakkanen, N. Norppa, M. Sorsa and H. Vaino. 1979.
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Dutkiewicz, T., and H. Tyras. 1967. Study of the skin absorption of ethyl-
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Engstrom, J., and R. Bjurstrom. 1978. Exposure to xylene and ethylbenzene.
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Ethylbenzene March 31, 1987
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Florin, I., L. Rutberg, M. Curvall and C.R. Enzell. 1980. Screening of
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