EPA-540/1-86-008
tnvironmental Protection
Agency
Office of Emergency and
Remedial Response
Washington DC 20460
Off'ce of Research and Development
Office of Health and Environmental
Assessment
Environmental Criteria and
Assessment Office
Cincinnati OH 45268
Superfund
&EPA
HEALTH EFFECTS ASSESSMENT
FOR ETHYLBENZENE
-------
EPA/540/1-86-008
September 1984
HEALTH EFFECTS ASSESSMENT
FOR ETHYLBENZENE
U.S. Environmental Protection Agency
Office of Research and Development
Office of Health and Environmental Assessment
Environmental Criteria and Assessment Office
Cincinnati, OH 45268
U.S. Environmental Protection Agency
Office of Emergency and Remedial Response
Office of Solid Waste and Emergency Response
Washington, DC 20460
U.S. Environmental Protection Agency
Region V, Library
230 South Dearborn Street
Chicago, Illinois 60604
-------
DISCLAIMER
This report has been funded wholly or In part by the United States
Environmental Protection Agency under Contract No. 68-03-3112 to Syracuse
Research Corporation. It has been subject to the Agency's peer and adminis-
trative review, and 1t has been approved for publication as an EPA document.
Mention of trade names or commercial products does not constltuHe endorse-
ment or recommendation for use.
U,S. Environmental Prctsction Agency
11
-------
PREFACE
This report summarizes and evaluates Information relevant to a prelimi-
nary Interim assessment of adverse health effects associated with ethyl-
benzene. All estimates of acceptable Intakes and carcinogenic potency
presented 1n this document should be considered as preliminary and reflect
limited resources allocated to this project. Pertinent toxlcologlc and
environmental data were located through on-Hne literature searches of the
Chemical Abstracts, TOXLINE, CANCERLINE and the CHEMFATE/DATALOG data bases.
The basic literature searched supporting this document 1s current up to
September, 1984. 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. 1980b. Ambient Water Quality Criteria Document for
Ethylbenzene. Environmental Criteria and Assessment Office, Cin-
cinnati, OH. EPA 400/5-80-048. NTIS PB81-117590.
U.S. EPA. 1985. Drinking Water Criteria Document for Ethylben-
zene. Prepared by the Environmental Criteria and Assessment Office,
Cincinnati, OH, OHEA for the Office of Drinking Water, Washington,
DC. Final draft.
The Intent 1n these assessments 1s to suggest acceptable exposure levels
whenever sufficient data were available. Values were not derived or larger
uncertainty factors were employed when the variable data were limited 1n
scope tending to generate conservative (I.e., protective) estimates. Never-
theless, the Interim values presented reflect the relative degree of hazard
associated with exposure or risk to the chemlcal(s) addressed.
Whenever possible, two categories of values have been estimated for sys-
temic toxicants (toxicants for which cancer 1s not the endpolnt of concern).
The first, the AIS or acceptable Intake subchronlc, 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 Hfespan). 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 1s
assumed. Animal data used for AIS 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.
111
-------
The AIC, acceptable Intake chronic, Is similar In concept to the ADI
(acceptable dally Intake). It 1s an estimate of an exposure level that
would not be expected to cause adverse effects when exposure occurs for a
significant portion of the Hfespan [see U.S. EPA (1980a) for a discussion
of this concept]. The AIC 1s route specific and estimates acceptable
exposure for a given route with the Implicit assumption that exposure by
other routes 1s Insignificant.
Composite scores (CSs) for noncardnogens have also been calculated
where data permitted. These values are used for ranking reportable quanti-
ties; the methodology for their development 1s explained 1n U.S. EPA (1983).
For compounds for which there 1s sufficient evidence of cardnogen1c1ty,
AIS and AIC values are not derived. For a discussion of risk assessment
methodology for carcinogens refer to U.S. EPA (1980a). Since cancer 1s a
process that 1s not characterized by a threshold, any exposure contributes
an Increment of risk. Consequently, derivation of AIS and AIC values would
be Inappropriate. For carcinogens, q-|*s have been computed based on oral
and Inhalation data 1f 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.
Data concerning the toxlcologlcal effects of ethylbenzene are extremely
limited. A major Issue of concern 1s limited data which suggest terato-
genlc/fetotoxlc effects of this compound. Inhalation exposures to ethyl-
benzene have resulted 1n fetotoxldty In rats and rabbits. A threshold
exposure level was not established and therefore neither an AIS nor an AIC
for Inhalation exposure was estimated.
Adequate Investigations are not available concerning teratogenlc/feto-
toxlc effects of oral exposure. However, the data on xylene/ethylbenzene
exposures suggest that If ethylbenzene 1s fetotoxlc, relatively high doses
should be required to produce these effects. The NOEL for fetotoxldty In
this study was 2.06 g/kg, even with only 17% of this mixture being ethyl-
benzene. The ethylbenzene dose administered was still higher than reported
NOELs for other endpolnts. Therefore, the NOEL from the only available oral
subchronlc study was used to estimate an oral AIS of 68 mg/day. An addi-
tional uncertainty factor of 10 was applied to estimate an oral AIC (6.8
mg/day). This corresponds to the estimate suggested by U.S. EPA (1985).
These estimates should be reviewed when more complete toxlcologlcal data,
especially chronic studies and gestatlonal exposures, are available.
-------
ACKNOWLEDGEMENTS
The Initial draft of this report was prepared by Syracuse Research
Corporation under Contract No. 68-03-3112 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 Air 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:
Judith Olsen and Erma Durden
Environmental Criteria and Assessment Office
Cincinnati. OH
Technical support services for the document series was provided by:
Bette Zwayer, Pat Daunt, Karen Mann and Jacky Bohanon
Environmental Criteria and Assessment Office
Cincinnati, OH
v1
-------
TABLE OF CONTENTS
1.
2.
3.
4.
5.
6.
7.
PPE
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
3.2. CHRONIC
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
4.3. OTHER RELEVANT DATA
4.4. WEIGHT OF EVIDENCE
REGULATORY STANDARDS AND CRITERIA
RISK ASSESSMENT
6.1. ACCEPTABLE INTAKE SUBCHRONIC (AIS)
6.1.1. Oral
6.1.2. Inhalation
6.2. ACCEPTABLE INTAKE CHRONIC (AIC)
6.2.1. Oral
6.2.2. Inhalation
REFERENCES
NDIX: Summary Table for Ethylbenzene
Page
1
. . . 3
. . . 3
, . . 3
. . . 4
. . . 4
. . . 4
, 6
. . . 6
. . . 6
7
. . . 8
. . . 8
. . . 8
. . . 8
. . . 8
. . . 9
. . . 10
10
. . . 10
. . . 10
. . . 11
. . . 11
. . . 11
. . . 13
. . . 19
-------
LIST OF ABBREVIATIONS
ADI
AIC
AIS
CNS
CS
LOAEL
LOEL
MED
NOAEL
NOEL
ppm
RQ
RVd
RVe
SCE
STEL
TLV
TWA
Acceptable dally Intake
Acceptable Intake chronic
Acceptable Intake subchronlc
Central nervous system
Composite score
Lowest-observed-adverse-effect level
Lowest-observed-effect level
Minimum effective dose
No-observed-adverse-effect level
No-observed-effect level
Parts per million
Dose at which the average respiratory rate Is
depressed 50%
Reportable quantity
Dose-rating value
Effect-rating value
Sister chromatld exchange
Short-term exposure limit
Threshold limit value
Time-weighted average
-------
1. ENVIRONMENTAL CHEMISTRY AND FATE
The relevant physical and chemical properties and environmental fate of
ethylbenzene (CAS No. 100-41-4) are given below.
Chemical class
Molecular weight
Vapor pressure
Water solubility
Log octanol/water partition
coefficient
Soil mobility
(predicted as retardation
factor for soil depth of
140 cm and organic carbon
content of 0.087%)
B1oconcentrat1on factor
Half-life 1n
A1r
Water
monocycllc aromatic
106.16 (Callahan et al.. 1979)
7 mm Hg at 20°C {Callahan et al.,
1979)
152 mg/j, at 20°C (Callahan et
al., 1979)
3.15 (Callahan et al., 1979)
<4 (estimated)
4.7 1n clam tissue, Tapes
semldecussata (Nunes and Benvllle,
1979)
35 hours (NAS, 1980)
1.5-7.5 days
(estimated)
A soil mobility factor has been estimated from the soil partition
coefficient value determined from the equation given by Schwarzenbach and
Westall (1981) and a comparison of the retardation factor values given by
WHson et al. (1981).
A half-life of ethylbenzene 1n water has been estimated on the basis of
the reaeratlon rate ratio of 0.465 and the oxygen reaeratlon rate of
0.19-0.96 day'1 (Mabey et al., 1981).
-1-
-------
A half-life value for ethylbenzene 1n soil could not be located 1n the
available literature. However, evaporation 1s expected to be the predomi-
nant loss mechanism from the soil surface. The half-life for soil evapora-
tion should be longer than the evaporation from water. Based on the b1o-
degradabllHy study of Tabak et al. (1981), ethylbenzene may blodegrade 1n
subsurface soil. Small amounts of ethylbenzene may also leach from soil
Into groundwater, particularly from sandy soils.
-2-
-------
2. ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS
2.1. ORAL
Although quantitative data regarding the absorption of ethylbenzene from
the gastrointestinal tract were not located 1n the available literature,
1ngest1on of ethylbenzene by rats has been reported to cause effects similar
to those produced by Inhalation of ethylbenzene by rats (Wolf et a!., 1956).
2.2. INHALATION
By measuring the amount of ethylbenzene that had to be added to maintain
a constant concentration In the chamber housing the experimental rats, Chin
et al. (1980) determined that young rats (100 g) absorbed 44% of the ethyl-
benzene to which they were exposed. Unfortunately, the authors did not
consider the percutaneous rate of absorption that occurred during their
experiment. Without explaining the derivation of their absorption coeffi-
cient, Bardodej and Bardodejova (1970) determined that human volunteers
(n=18) absorbed 64% of the total ethylbenzene to which they were exposed at
dose levels ranging from 100-370 mg/m3.
-3-
-------
3. TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS
3.1. SUBCHRONIC
In contrast to the target organs of acute ethylbenzene exposure, the CNS
and the lungs (Smyth et al., 1962; Faustov, 1958, 1960), the main effects of
subchronlc or chronic exposure to ethylbenzene by the oral and respiratory
routes appeared 1n the liver and kidneys (Wolf et al., 1956) (Table 3-1).
In rats and guinea pigs, the Increase In hepatic and renal weight caused by
ethylbenzene was accompanied by cloudy swelling of hepatocytes and renal
tubular epithelial cells (Wolf et al., 1956). Slight testlcular degenera-
tion caused by ethylbenzene exposure was described 1n rabbits and monkeys
(Wolf et al., 1956).
Russian studies have reported leukocytosls, decreased numbers of lympho-
cytes, Increased numbers of retlculocytes, and decreased albumins but
Increased globulins 1n serum as a result of exposure to 100 and 1000 mg/m3
of ethylbenzene for. 4 hours dally during a 7-month period (Ivanov, 1962).
Further details were not provided. In a subsequent paper, dystrophlc
changes 1n the liver and kidneys, muscle chronaxla and altered blood
chollnesterase activity were reported at an exposure level of 1000 mg/m3
(Ivanov, 1964). Faustov and Kramsakov (1968) reported decreased antibody
tHers 1n rabbits chronically exposed to ethylbenzene at a level of
1500 mg/m3.
3.2. CHRONIC
Pertinent data regarding the chronic Inhalation toxlclty of ethylbenzene
could not be located 1n the available literature.
-4-
-------
TABLE 3-1
Subchronlc Toxlclty of Ethylbenzene*
Route Vehicle
Oral olive oil
Inhalation NA
Inhalation NA
Inhalation NA
Inhalation NA
Exposure or Dose
control
13.6 ng/kg/day
136 mg/kg/day
408 mg/kg/day
680 mg/kg/day
control
400 ppm
(1737 mg/m»)
600 ppm
(2606 mg/m»)
1250 ppm
(5428 mg/m«)
2200 ppm
(9SOO mg/m«)
control
400 ppM
(1700 Mg/M»)
600 ppm
(2600 *g/m»)
1250 ppm
(5400 mg/M»)
400 ppm
(1700 mg/m*)
600 ppm
(2600 »g/m»)
1250 ppm
(5400 Mg/m*)
600 ppm
(2600 mg/m*}
400 ppM
(1700 mg/M»)
Duration
5 days/week for
6 Months or
130 days out of
182 days total
7 hours/day;
4-5 days/week.
103-138 days out
of 144-214 days
total
7 hours/day;
5 days/week for
186 days
7 hours/day;
138/214 days
7 hours/day;
5 days/week for
186 days
7 hours /day for
138/214 days
7 hours/day;
5 days/week for
186 days
Species
F /Ml star
rats
H/F rats
N only
guinea
pigs
F only
rabbits
F only
rhesus
Monkeys
Number Effects
Tested
10 None
10 None
10 None
10 Increased liver and kidney
10 weight; cloudy swelling In
hepatocytes and renal tubular
epithelium
10-25 None
Slight Increase In liver and
kidney weight
Slight Increase In liver and
kidney weight
Slight Increase In liver and
kidney weight; cloudy swelling
of hepatocytes and renal cells
Slight Increase In liver and
kidney weight; decreased
growth
5-10 None
None
Increased liver weight
Increased liver weight;
decreased growth
1-2 None
Slight degeneration In
testlcular germinal epithelium
None
1-2 Increased liver weight; slight
1 N testlcular degeneration
None
•Source: Wolf et al.. 1956
NA - Not applicable
-------
3.3. TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS
3.3.1. Oral. Administration of ethylbenzene which constituted 17% of a
xylene mixture 1n doses of 0.6, 1.2, 2.4, 3.0 or 3.6 mi/kg/day on days
6-15 of gestation was reported to be teratogenlc 1n mice at doses of >3
ml/kg (Marks et al. 1982). However, the dose levels are higher than the
level (291.43 mg/kg/day) which Is judged to be the lowest subchronlc LOAEL
(Section 6.1.1.). In addition, the mixture of xylene with ethylbenzene
precludes the use of the Marks et al. (1982) study 1n risk assessment, espe-
cially since xylene alone has been shown to be teratogenlc.
3.3.2. Inhalation. Pregnant New Zealand rabbits were exposed to ethyl-
benzene vapor at a dose level of 435 or 4348 mg/m3 for 6-7 hours/day on
days 1-24 of gestation (Hardln et al., 1981). On day 30 the rabbits were
killed; maternal organs were weighed and examined grossly and microscopic-
ally. Fetuses were weighed, sexed, measured for crown-rump length and
examined for external. Internal -and skeletal abnormalities. There was a.
statistically significant reduction 1n the number of live kits/Utter
(p<0.05) at both exposure levels, although the number of dead and resorbed
fetuses was not Increased above matched controls. Neither maternal toxldty
nor fetal malformations were evident.
Pregnant rats were exposed to ethylbenzene vapor at a dose level of 435
or 4348 mg/m3 for 6-7 hours/day on days 1-19 of gestation (Hardln et al.,
1981). On day 21 the rats were killed. At the higher dose level, maternal
toxldty was Indicated by Increased liver, kidney and spleen weights. A
statistically significant Increase 1n extra ribs (p<0.05) occurred In the
offspring of mothers exposed to both dose levels. The authors concluded
that the results of their experiment 1n rats suggested (rather than Indi-
cated) a teratogenlc potential for ethylbenrene.
-6-
-------
3.4. TOXICANT INTERACTIONS
Ethylbenzene constitutes =20% of technical grade xylene (Andersson et
al., 1981). When male Wlstar rats were exposed to m-xylene and ethylbenzene
(200 and 600 ppm, 6 hours/day for 5 days), the metabolism of m-xylene was
preferred to the metabolism of ethylbenzene (Elovaara et al., 1982). Ethyl-
benzene potentiates the toxldty of acrylonUrlle (Gut et al., 1981).
-7-
-------
4. CARCINOGENICITY
4.1. HUMAN DATA
Pertinent data regarding the cardnogenldty of ethylbenzene could not
be located on the available literature.
4.2. BIOASSAYS
Ethylbenzene 1s on the 11st of chemicals which have been deferred for
cardnogenldty testing (NTP, 1983).
4.3. OTHER RELEVANT DATA
Ethylbenzene, with or without activation by S-9, has been found not to
be mutagenlc to Salmonella typhlmurlum strains TA98, TA100, TA1535, TA1537
and TA1538 (Florin et al., 1980; Nestmann et al., 1980) or to Saccharomyces
cerevlslae strain D7 (Nestmann and Lee, 1983). At the highest dose tested,
ethylbenzene had a marginal effect 1n Inducing SCE after a 48-hour treatment
of human whole-blood lymphocytes in vitro (Norppa and Va1n1o, 1983). Four
common metabolites of ethylbenzene did not elldt a positive response 1n the
Ames bacterial assay (Salmona et al., 1976).
4.4. WEIGHT OF THE EVIDENCE
An IARC classification of ethylbenzene was not located. Based on the
criteria for weight of evidence proposed by the Carcinogen Assessment Group
of the U.S. EPA (Federal Register, 1984), since there appear to be no data
regarding the cardnogenldty of ethylbenzene 1n either humans or animals,
the chemical Is most appropriately designated a Group D-Not Classified
compound.
-8-
-------
5. REGULATORY STANDARDS AND CRITERIA
The ACGIH (1983) has recommended a TLV-TWA for ethylbenzene of TOO ppm
and a TLV-STEL of 125 ppm. OSHA currently limits occupational exposure to
ethylbenzene to a TWA concentration of 100 ppm (Code of Federal Regulations,
1981). The U.S. EPA (1980b) recommended a criterion level for drinking
water of 1.4 mg/8. based on the TLV.
-9-
-------
6. RISK ASSESSMENT
6.1. ACCEPTABLE INTAKE SUBCHRONIC (AIS)
6.1.1. Oral. In the only study available on oral exposure to ethyl-
benzene (Wolf et al.t 1956), the two lowest dose levels (13.6 and 136 mg/kg/
day) are NOELs and the other two dose levels (408 and 680 mg/kg/day) are
LOAELs. The highest NOEL (136 mg/kg/day) was used to compute the AIS.
Because the rats 1n this study (Wolf et al., 1956) were treated with ethyl-
benzene 5 days/week, the reported dose must be multiplied by 5 days/7 days
to reflect continuous exposure (97.14 mg/kg/day). To derive an AIS
(mg/day), the NOEL 1s multiplied by 70 kg and divided by an uncertainty
factor of 100 to account for the use of animal data In deriving human
criteria (Interspecles extrapolation) and the range of sensitivity 1n the
human population to any particular chemical. The oral AIS for ethylbenzene
exposure obtained through this calculation 1s 68.0 mg/day for a 70 kg human.
6.1.2. Inhalation. In the Wolf et al. (1956) study of Inhalation
exposure to ethylbenzene, the lowest exposure level tested (400 ppm; 1737
mg/m3) produced a slight Increase In liver and kidney weight 1n rats.
Other effects were produced at higher concentrations In the same tissues
(I.e., slight Increase 1n liver and kidney weights at 600 ppm, cloudy
swelling of hepatocytes and renal cells at 1250 ppm) and 1n other species
(Increased liver weight 1n guinea pigs and monkeys, and slight testlcular
degeneration 1n rabbits and monkeys at 600 ppm). Therefore, 1250 ppm would
be considered the LOAEL 1n the Wolf study. However, 1n the teratogenldty
study of Hardln et al. (1981), fetotoxlclty Indicated by a significantly
Increased number of extra ribs 1n the offspring of mothers exposed to ethyl-
benzene on days 1-19 of gestation occurred at an exposure level of 435
mg/m3 (100 ppm). A dose In mg/kg/day 1s estimated from exposure levels 1n
-10-
-------
mg/m3 by multiplying by an estimated rat Inhalation rate of 0.26 mVday,
dividing by the estimated body weight of a rat (0.35 kg) and converting
Intermittent exposure to an equivalent continuous exposure level. This
yields a continuous exposure dose of 663.26 mg/kg/day 1n the Wolf et al.
(1956) study and 87.52 mg/kg/day 1n the Hardln et al. (1981) study. The
lower LOAEL from the fetotoxldty study precludes the use of the higher
LOAEL from the subchronlc toxldty study for human risk assessment. Because
a NOEL for fetotoxldty has not been Identified and there 1s no NOAEL or
LOAEL from a subchronlc toxldty study lower than the LOAEL for fetotoxlc-
1ty, no criteria for subchronlc Inhalation exposure to ethylbenzene can be
derived at this time.
6.2. ACCEPTABLE INTAKE CHRONIC (AIC)
Because no chronic toxldty studies of ethylbenzene were located 1n the
available literature, the subchronlc toxldty study of Wolf et al. (1956)
was used to estimate chronic exposure criteria.
6.2.1. Oral. An additional uncertainty factor of 10 must be applied to
obtain an AIC from an AIS. Using an uncertainty factor of 1000, a chronic
oral ADI of 6.80 mg/human/day 1s calculated from the subchronlc NOEL 1n rats
of 97.14 mg/day Identified from the Wolf et al. (1956) study.
6.2.2. Inhalation. Because there are no experimental data on chronic
Inhalation of ethylbenzene and the subchronlc data are not adequate to use
1n human risk assessment, the TLV of 100 ppm (435 mg/m3), recommended by
the ACGIH (1983) and OSHA (Code of Federal Regulations, 1981), 1s considered
a NOEL for derivation of chronic ethylbenzene Inhalation criteria. The
exposure level of 435 mg/m3 1s converted to 44.4 mg/kg/day by multiplying
by the human breathing volume/8 hour workday (10 m3) and the fraction of
the total week spent at work (5/7 days), and dividing by the estimated human
-11-
-------
body weight (70 kg). However, the NOEL (44.4 mg/kg/day) derived from the
TLV 1s too close to the LOAEL (87.52 mg/kg/day) for fetotoxldty to be of
any use 1n human risk assessment. Therefore, no AIC for ethylbenzene
Inhalation exposure can be derived at this time.
An RQ has been calculated based on the Increased liver and kidney weight
of rats exposed to ethylbenzene by Inhalation. These effects were noted at
400 ppm (1737 mg/m3), 7 hours/day and 5 days/week for 144-214 days. The
human MED 1s calculated by expanding to continuous exposure, assuming a
human breathing rate of 20 mVday and an absorption factor of 0.5, and
applying an uncertainty factor of 5 to extrapolate from subchronlc to
chronic data. The resulting human MED, 724 mg/day, corresponds to an RV.
of 1.2. The RV associated with the effect of Increased liver and kidney
weights Is 4. A CS of 5, the product of RV. and RV , 1s calculated.
-12-
-------
7. REFERENCES
ACGIH (American Conference of Governmental Industrial Hyg1en1sts). 1983.
Threshold Limit Values for Chemical Substances and Physical Agents 1n the
Workroom Environment with Intended Changes for 1983-1984. Cincinnati, OH.
p. 20.
Andersson, K., K. Fuxe, O.G. NHsen, R. Toftgaard, P. Eneroth and J.A.
Gustafsson. 1981. Production of discrete changes 1n dopamlne and noradren-
allne levels and turnover 1n various parts of the rat brain following expo-
sure to xylene, ortho-, meta- and para-xylene, and ethylbenzene. Toxlcol.
Appl. Pharmacol. 60(3): 535-548. (Cited 1n U.S. EPA, 1985)
Bardodej, Z. and E. Bardodejova. 1970. Blotransformatlon of ethylbenzene,
styrene and alpha-methylstyrene 1n man. Am. Ind. Hyg. Assoc. J. 31(2):
206-209. (CH'ed 1n U.S. EPA, 1985)
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 440/4-79-029.
Chin, B.H., J.A. McKelvey, T.R. Tyler, L.J. Cal1st1, S.J. Kozbelt and L.J.
Sullivan. 1980. Absorption, distribution and excretion of ethylbenzene,
ethylcyclohexane and methylethylbenzene Isomers In rats. Bull. Environ.
Contam. Toxlcol. 24: 477-483. (Cited 1n U.S. EPA, 1985)
-13-
-------
Code of Federal Regulations. 1981. OSHA Safety and Health Standards. (29
CFR 1910.1000).
Elovaara, E., K. Engstroem and H. Va1n1o. 1982. Unaltered metabolism of
m-xylene 1n the presence of ethylbenzene. Rev. Blochem. 23: 265-268.
(Cited 1n U.S. EPA, 1984)
Faustov, A.S. 1958. Toxlclty of aromatic hydrocarbons. I. Comparative
toxldty of some aromatic hydrocarbons. II. Some problems of the toxic
hygiene properties of aromatic hydrocarbons. Tr. Voronezh. Med. Inst. 35:
247-255; 257-262. (CA 54:25279d) (Cited 1n U.S. EPA, 1985)
Faustov, A.S. 1960. Change of relative toxldty 1n a homologous series of
benzene derivatives related to the mean of entrance Into the organisms. Tr.
Voronezh. Med. Inst. 36: 243-245.. (CA 57:10148c) (Cited 1n U.S. EPA, 1985)
Faustov, A.S. and V.V. Kramsakov. 1968. Immunoblologlcal reactivity of an
organism during chronic poisoning with ethylbenzene and xylene. Tr.
Voronezh. Gos. Med. Inst. 73(4): 41-46. (CA 74:85860) (Cited 1n U.S. EPA,
1985)
Federal Register. 1984. Environmental Protection Agency. Proposed guide-
lines for carcinogenic risk assessment. 49 FR 46294-46299.
Florin, I., L. Rutberg, M. Curvall and C.R. Enzell. 1980. Screening of
tobacco smoke constituents for mutagenlclty using the Ames1 test. Toxi-
cology. 18: 219-232. (Cited 1n U.S. EPA, 1985)
-14-
-------
Gut, I., J. Kopecky, J. Nerudova, M. Krlvucova and L. Pelech. 1981. Meta-
bolic and toxic Interactions of benzene and acrylon1tr1le with organic sol-
vents. Ind. Environ. Xenoblotlcs, Proc. Int. Conf. p. 255-262. (Cited 1n
U.S. EPA, 1985}
Hardln, B.D., 6.P. Bond, M.R. Slkov, F.D. Andrew, R.P. Bellies and R.W.
N1eme1er. 1981. Testing of selected workplace chemicals for teratogenlc
potential. Scand. J. Work Environ. Health. 7(Suppl. 4): 66-75.
Ivanov, S.V. 1962. Changes 1n blood due to chronic poisoning with ethyl-
benzene vapors. Tr. Voronezh. Gos. Med. Inst. 47: 83-85. (CA 61:1163d)
(CHed In U.S. EPA, 1985)
Ivanov, S.V. 1964. Toxicology and hygienic rating of ethylbenzene content
1n the atmosphere of Industrial areas. G1g. Tr. Prof. Zabol. 8(2): 9-14.
(CA 61:3607e) (CHed 1n U.S. EPA, 1985)
Mabey, W.R., O.H. Smith, R.T. Podoll, et al. 1981. Aquatic Fate Process
Data for Organic Priority Pollutants. Monitoring and Data Support D1v.,
Office of Water Regulations and Standards, Washington, DC. EPA 440/4-81-014.
Marks, T.A., T.A. Ledoux and J.A. Moore. 1982. Teratology of a commercial
xylene mixture 1n the mouse. J. Toxlcol. Environ. Health. 9(1): 97-106.
NAS (National Academy of Sciences). 1980. The Alkyl Benzenes. Committee
on Alkyl Benzene Derivatives, NRC, NAS, Washington, DC.
-15-
-------
Nestmann, E.R. and E.G.H. Lee. 19&3. Mutagenldty of constituents of pulp
and paper mm effluent 1n growing cells of Saccharomyces cerevlslae.
Mutat. Res. 119(3-4): 273-280.
Nestmann, E.R., E. G.H. Lee, T.I. Matula, G.R. Douglas and 3.C. Mueller.
1980. Mutagenldty of constituents Identified 1n pulp and paper mill ef-
fluents using the Salmone11a/mammal1an-m1crosome assay. Mutat. Res. 79:
203-212. (Cited 1n U.S. EPA, 1985)
Norppa, H. and H. Va1n1o. 1983. Induction of slster-chromatld exchanges by
styrene analogs 1n cultured human lymphocytes. Mutat. Res. 116(3-4):
379-387.
NTP (National Toxicology Program). 1983. National Toxicology Program.
Toxicology Testing Program. Chemicals on Standard Protocol: Management
Status. December 6.
Nunes, P. and P.E. Benvllle. 1979. Uptake and depuration of petroleum
hydrocarbons 1n the Manlta clam, Tapes semldecussata. Bull. Environ.
Toxlcol. 21: 719-726.
Salmona, M., J. Pachecka, L. Cantonl, G. Belvedere, E. Muss1n1 and S.
Garatt1n1. 1976. Mlcrosome styrene mono-oxygenase and styrene epoxlde
hydrase activities 1n rats. Xenoblotlca. 6: 585-591. (Cited 1n U.S. EPA,
1980b)
-16-
-------
Schwarzenbach, R.P. and J. Westall. 1981. Transport of nonpolar organic
compounds from surface water to groundwater. Laboratory sorptlon studies.
Environ. Sc1. Techno!. 15: 1360-1367.
Smyth, H.F., C.P. Carpenter, C.S. Well, U.C. Pozzanl and J.A. Strlegel.
1962. Range-finding toxldty data. List VI. Am. Ind. Hyg. Assoc. J. 23:
95. (Cited 1n U.S. EPA, 1985)
Tabak, H.H., S.A. Quare, C.I. Mashnl and E.F. Barth. 1981. Blodegrad-
abllHy studies with organic priority pollutant compounds. J. Water Pollut.
Control Fed. 53: 1503-1518.
U.S. EPA. 1980a. Guidelines and Methodology Used 1n the Preparation of
Health Effects Assessment Chapters of the Consent Decree Water Quality
Criteria. Federal-Register. 45:79347-79357.
U.S. EPA. 1980b. Ambient Water Quality Criteria Document for Ethylbenzene.
Environmental Criteria and Assessment Office, Cincinnati, OH. EPA
400/5-80-048. NTIS PB 81-117590.
U.S. EPA. 1983. Methodology and Guidelines for Reportable Quantity Deter-
minations Based on Chronic Toxldty Data. Prepared by the Environmental
Criteria and Assessment Office, Cincinnati, OH, OHEA for the Office of Solid
Waste and Emergency Response, Washington, DC.
-17-
-------
U.S. EPA. 1985. Drinking Water Criteria Document for fcthylbenzene. Pre-
pared by the Environmental Criteria and Assessment Office, Cincinnati, OH,
OHEA for the Office of Drinking Water, Washington, DC. Final draft.
WHson, J.T., C.G. Enfleld, W.J. Dunlap, R.L. Cosby, D.A. Foster and L.B.
Baskln. 1981. Transport and fate of selected organic pollutants In a sandy
soil. J. Environ. Qual. 10: 501-506.
Wolf, M.A., V.K. Rowe. D.D. McColHster, R.L. Holllngsworth and F. Oyen.
1956. lexicological studies of certain alkylated benzenes and benzene.
Arch. Ind. Health. 14: 387-398. (Cited 1n U.S. EPA, 1985)
U.S. Environmental Protection Agency.
Region V, Library
230 South Dearborn Street
Chicago, Illinois 60604
-18-
-------
APPENDIX
Summary Table for Ethylbenzene
10
I
Inhalation
AIS
AIC
Maximum
composite
score
Oral
AIS
AIC
Species Experimental
Dose/Exposure
NA NA
NA NA
rats 400 ppm
(1737 mg/m8)
7 hours/day.
5 days/week for
144-214 days
(RVd = 1.2)
rats 136 mg/kg/day,
5 days/week, TWA=
97.14 mg/kg/day
rats 136 mg/kg/day,
5 days/week, TWA=
97.14 mg/kg/day
Effect
NA
NA
Increased liver and
kidney weights
(RVe - 4)
Increased liver and
kidney weights with
cloudy swelling
NA
Acceptable Intake Reference
(AIS or AIC)
NO NA
ND NA
5 Wolf et al..
1956
68.0 mg/day Wolf et al.,
1956
6.80 mg/day Wolf et al.,
1956
NO = Not derived; NA = not available
------- |