Draft Ethylbenzene HEAC Assessment/PEL Recommendation
Prepared by Julia Quint, Ph.D., HEAC Member
Initial Draft = 10/08; Revised draft = 10/09
DRAFT
Ethylbenzene HEAC Assessment and PEL Recommendation
October 20, 2009
Substance name: Ethylbenzene
CAS #: 100-41-4 Molecular weight: 106.16
Synonyms: Ethylbenzol; Phenylethane
Molecular formula: C8H10 Structural formula:
ppm to mg/m3 conversion at 25 º C and 760 torr: 1 ppm = 4.3 mg/m3; 1 mg/m3 = 0.23 ppm
Physical characteristics: Colorless, flammable liquid with an aromatic odor. The odor threshold is 2.3 ppm.
Special physical characteristics: Boiling point = 132.2 º C. Vapor pressure = 7.1 torr at 20º C. Air saturated with
ethylbenzene vapor at 26º C and 760 torr contains 1.32% ethylbenzene. It is a dangerous fire risk. Solubility: Practically
insoluble in water; miscible with alcohol and ether; soluble in carbon tetrachloride and benzene.
Flammability and other hazards: Flash point = 18º C, closed cup. Explosive limits: lower, 1%; upper, 6.7% by volume
in air. Auto ignition temperature: 432.22º C. Exposure to ignition sources such as heat, sparks, or open flame may create a
fire or explosion hazard. Contact of ethylbenzene with strong oxidizing agents should be avoided.
Major commericial forms: Based on a review of product MSDSs, commercial forms include: liquids, aerosols, tubes,
cartridges, and pastes. Example products and their ethylbenzene content are listed below.
Product Commercial Form % Ethylbenzene
98610-H HI FI Sparkling Blue Lacquer Liquid Not given (primary ingredient)
319756-3, Natural Rubber Cement Liquid 10-20
Step 2 Rust Stopper Rust Preventive Aerosol 15-20
Carb Medic Carb/Choke/Valve Cleaner Aerosol 5-15
Westleys Citrus Tar and Bug Remover Aerosol 18-20
All-Weather® Plastic Tag Marker Solid 7-13
Polyseamseal Outdoor Clear Sealant Cartridge <5
Xylol Klean Stripper Liquid 15-20
Quikrete Polyurethane Non-Sag Sealant No. 8660-11 Paste 0.1-1
Sherwin-Williams Wood Classics Fast Dry Oil Varnish, Satin Liquefied Gas 0.6
Product Commercial Form % Ethylbenzene
Page 1 of 18
Draft Ethylbenzene HEAC Assessment/PEL Recommendation
Prepared by Julia Quint, Ph.D., HEAC Member
Initial Draft = 10/08; Revised draft = 10/09
OSI Pro Series Quad Advanced Formula Sealant Tube <5
Sprayway Automotive Carburetor and Choke Cleaner No. 720 Aerosol 15-25
Uses/Applications: Ethylbenzene is used as an intermediate in the production of styrene, as a solvent, and in the plastic
and rubber industries. Industrial grade xylene contains approximately 20% ethylbenzene. Occupational exposure to
ethylbenzene can occur during its use as a chemical intermediate and in industries where products containing ethylbenzene
are used such as auto repair, construction, painting, and health care (histology laboratories).
Current Occupational Exposure Limits (Time-weighted average or TWA)
Organization TWA Notation/Other Information
(ppm)
Cal/OSHA 100 125 STEL
OSHA 100 125 STEL
NIOSH 100 125 STEL
American Conference of Governmental Industrial 100 125 STEL (1976-present); A3* (2002)
Hytgienists (ACGIH) (1967- *Confirmed animal carcinogen with unknown relevance to
present) humans
Biological Exposure Index (BEI) = 1.5 g mandelic acid
(urine)/g creatinine.
Australia 100 125 ppm Short Term Exposure Limit (STEL)
Belgium 100 125 ppm STEL; Skin
Brazil 78
Canada (Alberta, Quebec) 100 125 ppm STEL
Canada (British Columbia) 100 125 ppm STEL; A3; Skin
China 100 150 ppm STEL
Czech Republic 200 500 ppm STEL; Skin
EU-IOELV 100 200 ppm STEL; Skin
Finland 50 200 ppm; Skin
Germany MAK None 3A (Carcinogen); Skin
Hong Kong 100 125 ppm STEL
International Agency for Research on Cancer (IARC) 2B
Ireland 100 125 ppm STEL; Skin
Japan 50 2B; provisional 2001
Malaysia 100
Mexico 100 125 ppm STEL
Netherlands 50 100 ppm STEL; Skin
New Zealand 100 125 ppm STEL
Norway 5 Ca; Skin
Poland 100 350 ppm STEL; Skin
South Africa DOL RL 100 125 ppm STEL
Spain 100 200 ppm; Skin
United Kingdom 100 125 ppm STEL; Skin
Organizational Sources and Recommendations
ACGIH Threshold Limit Value (TLV) Findings/Conclusions
100 ppm TWA; 125 STEL; A3 The Ethylbenzene TLV Documentation Summary states, in part:
ACGIH TLV Documentation (2002)
A TLV-TWA of 100 ppm and a TLV-STEL of 125 ppm are recommended
to minimize the potential risks of disagreeable irritations. An A3, Animal Carcinogen with Unknown Relevance to
Humans notation is assigned based on a significant increase in renal tubular adenoma/carcinoma in rats and alveolar and
bronchiolar adenoma/carcinoma in mice exposed by inhalation to ethylbenzene.
Page 2 of 18
Draft Ethylbenzene HEAC Assessment/PEL Recommendation
Prepared by Julia Quint, Ph.D., HEAC Member
Initial Draft = 10/08; Revised draft = 10/09
Ethylbenzene is an irritant of the skin and mucuous membrane and appears to have acute depressant effects on the central
nervous system (CNS). Potential chronic health hazards include damage to the liver and kidneys. No systemic toxicity or
increased risk of cancer is expected at ethybenzene exposure concentrations in workplace air less than those that produce
distinctly disagreeable skin and eye irritation.
Disagreeable Irritations—TLV Basis
Bardodej and Bardodejova, 1961 was cited as the basis for the ethylbenzene TLV. The article was published in a non-
English journal and was not available for review. The study was described in the TLV Documentation as a controlled
inhalation metabolism study (single 8-hour exposure) in which no adverse effects were observed during a 100-ppm
exposure. At 184 ppm, respiratory tract irritation, conjunctivitis, and drowsiness were common.
Other Cited Irritation Studies
Yant et al., 1930
ACGIH cited this study to describe the following: transient eye irritation experienced by six subjects exposed to 200 ppm
ethylbenzene, and eye irritation with profuse lacrimation at 1000 ppm, with tolerance developing. At 2000 ppm, eye
irritation and lacrimation were immediate and severe and were accompanied by moderate nasal irritation, constriction in the
chest, and vertigo; 5000 ppm produced intolerable irritation to the eyes and nose.
A comprehensive search of the literature produced no additional human studies of ethylbenzene-induced irritant effects.
Chronic Health Hazards—Liver and Kidney Damage
Wolf et al., 1956
This study was cited to support the potential chronic effects of ethylbenzene on the liver and kidney. It was not available
for review. The following description of the study is based on information in the TLV Documentation: repeated oral
administration of ethylbenzene to female rats 5 days/week for a period of six months at doses of 13.6 or 136 mg/kg/day
produced no effect in the animals. At doses of 408 or 608 mg/kg/day, slight increases in both kidney and liver weights
were found, accompanied by slight pathologic changes in these organs. The pathologic changes were described as cloudy
swelling of the tubular epithelium of the kidney and cloudy swelling of the parenchymal cells of the liver. No effect upon
the hematopoietic system was noted.
Carcinogenicity
U.S. National Toxicology Program (NTP), 1996
The ACGIH A3 notation was based on a draft report of an NTP cancer bioassay in which rats and mice of both sexes were
exposed by inhalation 6 hours/day, 5 days/week for 104 weeks at 0, 75, 250, or 750 ppm ethylbenzene. The TLV
Documentation describes the findings as follows: At the highest exposure level, tumors (adenomas and carcinomas) of the
renal tubules were significantly increased in male rats. Upon step-sectioning, tumors of the renal tubules were also
increased in female rats. Interstitial cell adenomas were also significantly increased in the 750-ppm male rats. In the 750-
ppm male mice, the incidences of alveolar/bronchiolar adenomas and carcinomas (combined) were greater than those of
controls but still within the historical control range. In the 750-ppm female mice, hepatocellular adenomas and carcinomas
(combined) were greater than in controls but were also within historical control ranges.
Page 3 of 18
Draft Ethylbenzene HEAC Assessment/PEL Recommendation
Prepared by Julia Quint, Ph.D., HEAC Member
Initial Draft = 10/08; Revised draft = 10/09
Discussion and Assessment
The ACGIH TLV of 100 ppm is based on disagreeable irritations. The cited study from which the NOAEL was identified,
Bardodej and Bardodejova, 1961, was not available for review. However, the description of the study as a ―controlled
inhalation metabolism study (single 8-hour exposure)‖, suggests that it may be limited in scope.
ACGIH concluded that the TLV of 100 ppm also protects against systemic toxicity and increased risk of cancer. The basis
for the conclusion that chronic exposure to 100 ppm ethylbenzene will not damage the liver or kidneys, presumably is based
on the NOAEL of 136 mg/kg/day (200 ppm) ethylbenzene identified in the Wolf et al., 1956 study.
As indicated by the A3 notation, ACGIH identifies ethylbenzene as a confirmed carcinogen in animals with no relevancy to
humans. The A3 notation is defined by ACGIH as ―the agent is carcinogenic in experimental animals at a relatively high
dose, by route(s) of administration, at site(s), of histologic type(s), or by mechanism(s) that may not be relevant to worker
exposure. Available epidemiologic studies do not confirm an increased risk of cancer in exposed humans. Available
evidence does not suggest that the agent is likely to cause cancer in humans except under uncommon or unlikely routes or
levels of exposure. The only information in the TLV Documentation that explains assignment of the A3 designation for
ethylbenzene, is the statement: ―NTP has not reported any mechanistic investigations on the relatively weak carcinogenicity
of ethylbenzene‖.
PEL based on ACGIH-Identified Irritation Study
100 ppm (study NOAEL) ÷ 3 (Intraspecies Uncertainty Factor*) (UF) = 30 ppm (Bardodej and Bardodejova, 1961)
PEL based on ACGIH-Identified Chronic, Oral Toxicity (Liver and Kidney Damage) Study (Wolf et al., 1956)
136 mg/kg/day or 200 ppm (study NOAEL) ÷ 3 (Interspecies UF ) ÷ 3 (Intraspecies UF*) = 20 ppm
§
136 mg/kg/day or 200 ppm (study NOAEL) ÷ 6 (Interspecies UF ) ÷ 3 (Intraspecies UF*) = 11 ppm
§§
136 mg/kg/day or 200 ppm (study NOAEL) ÷ 10 (Interspecies UF ) ÷ 3 (Intraspecies UF*) = 7 ppm
PEL based on 2007 Sub-Chronic (13 week), Oral Toxicity (Liver and Kidney Damage) Study (Mellert and Deckardt,
2007)
75 mg/kg/day or 110 ppm (study NOAEL) ÷ 3 (Subchronic UF ) ÷ 3 (Interspecies UF) ÷ 3 (Intraspecies UF*) = 4 ppm
§
75 mg/kg/day or 110 ppm (study NOAEL) ÷ 3 (Subchronic UF ) ÷ 6 (Interspecies UF ) ÷ 3 (Intraspecies UF*) = 2 ppm
§§
75 mg/kg/day or 110 ppm (study NOAEL) ÷ 3 (Subchronic UF ) ÷ 10 (Interspecies UF ) ÷ 3 (Intraspecies UF*) = 1 ppm
*Based on potential differences in the ability of workers to metabolize ethylbenzene via the cytochrome P450 enzyme
CYP2E1(Sams et al., 2004). CYP2E1 is known to have a wide variation within human populations, primarily due to
enzyme induction in response to fasting, diabetes, or alcohol consumption (Kadlubar and Guengerich, 1992). CYP2E1
activity can also be inhibited in vivo either by dietary intake of alcohol and chemicals such as diallyl sulphate from garlic
(Loizou and Crocker, 2001), or by pharmaceuticals such as chlormethiazole (Gebhardt et al., 1997) and disulfaram
(Kharasch et al., 1993).
Application of intraspecies UFs in occupational health studies is also consistent with OSHA policy. OSHA (1989) states:
―…if the available data include a NOEL derived from a well-conducted human study, a smaller safety factor might be used
to establish an exposure limit than would be used if the data to be used to establish the limit consisted of a NOEL from an
animal study; in the latter case, there is greater uncertainty regarding the relationship between the animal NOEL and
human NOEL. Safety factors have also been used to recognize the fact that the human population is heterogeneous and
that there may be a wide variation in individual responses to toxic substances (the wide range in the odor thresholds
reported for some substances is a good illustration of individual variability in response).‖
Page 4 of 18
Draft Ethylbenzene HEAC Assessment/PEL Recommendation
Prepared by Julia Quint, Ph.D., HEAC Member
Initial Draft = 10/08; Revised draft = 10/09
Based on OEHHA 2000 and OEHHA 2007.
§
Based on OEHHA 2008. In the current, draft Hot Spots risk assessment guidelines for deriving noncancer reference
exposure levels, the interspecies UF is increased from 3 to 6.
Based on OEHHA 2000 , OEHHA 2007, and OEHHA 2008. Exposure for 13 weeks or less (8 to 12% of a rat’s expected
lifetime) is designated as a subchronic exposure, and a 3-fold UF is used to adjust for chronic exposure.
§§
Based on OSHA 1993. In the noncancer risk assessment for glycol ethers, OSHA applied an interspecies UF of 10.
Organizational Sources and Recommendations (Continued)
Cal/EPA Office of Findings / Conclusions
Environmental Health Hazard
Assessment (OEHHA) Based on the requirements of the Air Toxics Hot Spots Information and
Unit Risk Value (Cancer) Assessment Act of 1987 (Health and Safety Code Section 44300 et seq.),
2.5 x 10-6 (g/m3)-1 OEHHA adopted a unit risk value for ethylbenzene. The value, 2.5 x 10-6
(g/m3)-1, is based on the incidence of kidney cancer (renal tubule adenoma or
Cal/EPA OEHHA
carcinoma) in male rats in an NTP study (NTP, 1999; Chan et al., 1998). The
Notice of Adoption of Unit
OEHHA risk assessment document (OEHHA 2007a) describes derivation of the
Risk Value for Ethylbenzene
unit risk value. The document underwent public and peer review, and was
November 14, 2007
approved by the Scientific Review Panel for Toxic Air Contaminants.
NTP Cancer Bioassay
In the NTP study, groups of 50 animals were exposed via inhalation to 0, 75,
250 or 750 ppm ethylbenzene for 6.25 hours per day, 5 days per week for 104 (rats) or 103(mice) weeks. For male rats in
the 75 ppm and 250 ppm exposure groups, survival probabilities at the end of the study were comparable to that of controls
but significantly less for male rats in the 750 ppm exposure group (30% for controls and 28%, 26% and 4% for the 75 ppm,
250 ppm and 750 ppm exposure groups, respectively). In female rats, survival probabilities were comparable in all groups
(62% for controls and 62%, 68% and 72% for the 75 ppm, 250 ppm and 750 ppm exposure groups, respectively).
Cancer Bioassay Results
The incidences of renal tumors (adenoma and carcinoma in males; adenoma only in females) were significantly increased
among rats of both sexes in the high-dose group (males: 3/50, 5/50, 8/50, 21/50; females: 0/50, 0/50, 1/50, 8/49 in control,
75 ppm, 250 ppm and 750 ppm groups, respectively [standard and extended evaluations of kidneys combined]). NTP
concluded that there was clear evidence of carcinogenicity in male rats and some evidence in female rats, based on the
findings.
Increased incidences of alveolar /bronchiolar adenoma or carcinoma (combined) were observed in male mice in the high-
dose group (7/50, 10/50, 15/50, 19/50 in control, 75 ppm, 250 ppm and 750 ppm groups, respectively). Among female
mice in the high-dose group, the incidences of combined heptocellular adenoma or carcinoma and hepatocellular adenoma
alone were significantly increased over control animals (for adenomas and carcinomas the tumor incidences were 13/50,
12/50, 15/50, 25/50 in control, 75 ppm, 250 ppm, and 750 ppm groups, respectively). NTP concluded that these findings
proved some evidence of carcinogenicity in male and female mice.
Unit Risk Value Derivation Method
OEHHA used the linearized multistage (LMS) methodology with lifetime weighted average (LTWA) doses from the male
rat renal tumor data to derive the unit risk value for ethylbenzene. OEHHA indicated that the unit risk value based on
PBPK internal doses was not markedly different than the value based on the LTWA doses, and involved a number of
assumptions. Because the PBPK modeling is uncertain and the results were relatively insensitive to the approach used,
OEHHA selected the LMS results based on the LTWA doses as most appropriate.
Page 5 of 18
Draft Ethylbenzene HEAC Assessment/PEL Recommendation
Prepared by Julia Quint, Ph.D., HEAC Member
Initial Draft = 10/08; Revised draft = 10/09
Mode of Action (MOA) for Ethylbenzene Carcinogenesis
OEHHA did not determine a convincing MOA for any of the tumor sites evaluated in the risk assessment report. OEHHA
also found no basis to support suggested MOAs for ethylbenzene-induced rodent tumors such as increased incidence of
and/or severity of chronic progressive nephropathy (CPN), a common process in aged rats (Hard, 2002), or an increase in
eosinophilic foci in liver as a mechanism for production of liver tumors. OEHHA concluded that the limited data do not
conclusively establish any particular MOA for ethylbenzene carcinogenesis. This is consistent with EPA guidance which
states that conflicting data and data gaps often require careful evaluation before reaching any conclusions with respect to a
prospective MOA (EPA, 1996). OEHHA stated, however, that one or more genotoxic processes (such as oxidative DNA
damage resulting from genotoxic epoxide metabolites) appear at least plausible and may well contribute to the overall
process of tumor induction. Because of this, they used the default linear approach for extrapolating the dose-response curve
to low doses (OEHHA, 2007a).
Discussion and Assessment
Comments and Response to Comments—Ethylbenzene Unit Risk Value
The American Chemistry Council submitted extensive comments on the OEHHA Ethylbenzene Risk Assessment
Document that described derivation of the unit risk value. The Council’s comments focused primarily the organization’s
scientific disagreements with OEHHA’s conclusions regarding the MOA for ethlybenzene carcinogenesis, and use of the
linearized multistage (LMS) methodology to derive the unit risk value. The Western States Petroleum Association
submitted similar comments.
The submitted comments and OEHHA’s comprehensive responses to the comments are attached. They also can be
accessed from the OEHHA website at www.oehha.ca.gov/air/hot_spots/pdf/respethyl082707.pdf - 2007-10-04.
OEHHA’s response to comments based on a March 28, 2008 Notice of Proposed Rulemaking to adopt a No Significant
Risk Level (NSRL) for ethylbenzene based on carcinogenicity can be accessed at
http://oehha.ca.gov/Prop65/law/pdf_zip/NSRLethyl050709.pdf
PEL Based on the Ethylbenzene Unit Risk Value Derived by OEHHA (OEHHA, 2007a)
(1) Estimated excess lifetime cancer risk:
PEL (mg/m3) x unit risk value (mg/m3)-1 x [10 m3/20 m3 x 250 days/365 days x 40 yrs/70 yrs]*
*adjustment for occupational exposure
434 mg/m3 x 2.5x10-3 (mg/m3)-1 x 10 m3/20 m3 x 250 days/365 days x 40 years/70 years = 21x10-2
(2) Estimated Excess Cancer Cases Per 1,000 Workers at Current PEL (100 ppm or 434 mg/m3) = 210
(3) PEL = 0.5 ppm (100 ppm/210) to reduce cancer risks to 1 excess cancer case/1,000 workers exposed to ethylbenzene
over their working lifetimes.
Organizational Sources and Recommendations (Continued)
Cal/EPA OEHHA Findings/Conclusions
Chronic Reference Exposure
Level (cREL) The OEHHA cREL (OEHHA, 2000b) is based on the NTP lifetime
2,000 µg/m3 (0.4 ppm) toxicity/carcinogenesis study (NTP, 1999). The NOAEL for non-neoplastic
Critical effect: liver, kidney, effects in the study was 75 ppm, and the LOAEL was 250 ppm. The non-
pituitary gland in mice & rats neoplastic effects observed at 250 ppm ethylbenzene included nephrotoxicity,
Hazard index target(s):
alimentary
Page 6 of 18 system (liver);
kidney; endocrine system
Draft Ethylbenzene HEAC Assessment/PEL Recommendation
Prepared by Julia Quint, Ph.D., HEAC Member
Initial Draft = 10/08; Revised draft = 10/09
body weight reduction (rats), hyperplasia of the pituitary gland; liver cellular
alterations and necrosis (mice).
The NTP cancer study is described above (see page 5).
Discussion and Assessment
OEHHA stated that the EPA inhalation RfC for ethylbenzene (summarized below) is based on developmental toxicity
(EPA, 1991). They pointed out that if their noncancer risk assessment methodology is followed using the same
developmental NOAEL that EPA used, the RfC would be 0.6 ppm; the cREL of 0.4 ppm would also protect against
developmental toxicity.
PEL based on chronic health effects (kidney, liver, etc.) used by OEHHA to derive the ethylbenzene cREL (NTP, 1999)
75 ppm (NOAEL) ÷ 3 (Interspecies UF ) ÷ 3 (Intraspecies UF*) = 7.5 ppm
§
75 ppm (NOAEL) ÷ 6 (Interspecies UF ) ÷ 3 (Intraspecies UF*) = 4 ppm
§§
75 ppm (NOAEL) ÷ 10 (Interspecies UF ) ÷ 3 (Intraspecies UF*) = 2.5 ppm
Based on OEHHA 2000 and OEHHA 2007.
*Based on potential differences in the ability of workers to metabolize ethylbenzene via the cytochrome P450 enzyme
CYP2E1(Sams et al., 2004). CYP2E1 is known to have a wide variation within human populations, primarily due to
enzyme induction in response to fasting, diabetes, or alcohol consumption (Kadlubar and Guengerich, 1992). CYP2E1
activity can also be inhibited in vivo either by dietary intake of alcohol and chemicals such as diallyl sulphate from garlic
(Loizou and Crocker, 2001), or by pharmaceuticals such as chlormethiazole (Gebhardt et al., 1997) and disulfaram
(Kharasch et al., 1993).
Application of intraspecies UFs in occupational health studies is also consistent with OSHA policy. OSHA (1989) states:
―…if the available data include a NOEL derived from a well-conducted human study, a smaller safety factor might be
used to establish an exposure limit than would be used if the data to be used to establish the limit consisted of a NOEL
from an animal study; in the latter case, there is greater uncertainty regarding the relationship between the animal NOEL
and human NOEL. Safety factors have also been used to recognize the fact that the human population is heterogeneous
and that there may be a wide variation in individual responses to toxic substances (the wide range in the odor thresholds
reported for some substances is a good illustration of individual variability in response).‖
§
Based on OEHHA 2008. In the current, draft Hot Spots risk assessment guidelines for deriving noncancer reference
exposure levels, the interspecies UF is increased from 3 to 6.
§§
Based on OSHA 1993. In the noncancer risk assessment for glycol ethers, OSHA applied an interspecies UF of 10.
Organizational Sources and Recommendations (Continued)
U.S. EPA Inhalation Reference Findings/Conclusions
Concentration (RfC)
1 mg/m3 (0.33 ppm) The EPA RfC for ethylbenzene is based on a NOAEL of 100 ppm identified
Developmental toxicity from inhalation developmental toxicity studies in rats and rabbits (Andrew et
Integrated Risk Information al., 1981; Hardin et al., 1981; U.S. EPA, 1991).
System (IRIS) Online
1991 Methods
Wistar rats (n=78-107/concentration) and New Zealand white rabbits (n=29-
30/concentration) were exposed by inhalation 6 to 7 hours/day, 7 days/week
during days 1-19 and 1-24 of gestation, respectively, to 0, 100, or 1000 ppm
Page 7 of 18
Draft Ethylbenzene HEAC Assessment/PEL Recommendation
Prepared by Julia Quint, Ph.D., HEAC Member
Initial Draft = 10/08; Revised draft = 10/09
ethylbenzene. A separate group of rats was exposed pregestationally for 3 weeks prior to mating and exposure was
continued into the gestational period. All pregnant animals were sacrificed 1 day prior to term (21 days for rats; 30 days for
rabbits). Maternal organs were examined histopathologically. Uteri were examined and fetuses were weighed, sexed, and
measured for crown-to-rump length, and examined for external, internal and skeletal abnormalities.
Results
Ethylbenzene did not cause embryotoxicity, fetotoxicity, or teratogenicity in rabbits at either exposure level. There were no
significant incidences of major malformations, minor anomalies, or common variants in fetal rabbits from exposed groups.
Maternal toxicity in the rabbits was not evident. The results indicated a NOAEL of 100 ppm based on the lack of
developmental effects in rabbits.
In rats exposed only during gestation, there were no histopathological effects in any of the maternal organs examined.
There was no effect on fertility or on any of the other measures of reproductive status. The principal observation in fetuses
was an increased incidence (p < 0.05) of supernumerary and rudimentary ribs in the high exposure group and an elevated
incidence of extra ribs in both the high and 100 ppm groups. Both absolute and relative liver, kidney, and spleen weights
were significantly increased in pregnant rats from the 1000 ppm group.
Groups of female rats were also exposed for 3 weeks prior to mating and exposure was continued during gestation. Like
the 1000-ppm group exposed only during gestation, there was also an increased incidence of extra ribs (p < 0.05) in the pre-
gestationally exposed high exposure group. However, an increased incidence was not seen at 100 ppm in those exposed
pre-gestationally, in contrast to the comparable group exposed only during gestation. There was no increase in rudimentary
ribs in either of the exposed groups. The apparent discrepancy in the incidence of supernumerary ribs between the
pregestionally-exposed group and those exposed only during gestation was thought to be based, in part, on the fewer
numbers of litters examined in the pregestionally-exposed group. The NOAEL was identified as 100 ppm, and 1000 ppm
was considered a LOAEL for the rat study.
Discussion and Assessment
EPA applied a cumulative UF of 300 to the 434 mg/m3 NOAEL to derive the RfC of 1 mg/m3 (0.33 ppm). The 300 UF
reflects a factor of 10 to adjust for the absence of multigeneration reproductive and chronic studies.
As described below, more recent inhalation developmental and reproductive toxicity studies using ethylbenzene exposure
levels between 100 ppm and 1000 ppm, have established higher NOAELs.
PEL based on developmental toxicity studies used by EPA to derive the ethylbenzene RfC (Andrew et al., 1981; Hardin et
al., 1981)
100 ppm (NOAEL) ÷ 3 (Interspecies UF ) ÷ 10 (Intraspecies**) = 3 ppm
§
100 ppm (NOAEL) ÷ 6 (Interspecies UF ) ÷ 10 (Intraspecies**) = 2 ppm
§§
100 ppm (NOAEL) ÷ 10 (Interspecies UF ) ÷ 10 (Intraspecies**) = 1 ppm
Based on OEHHA 2000 and OEHHA 2007.
** Based on protecting the developing fetus upon which, according to OSHA, the ―healthy worker effect‖ is not necessarily
conferred (OSHA, 1993).
Also based on potential differences in the ability of workers to metabolize ethylbenzene via the cytochrome P450
enzyme CYP2E1(Sams et al., 2004). CYP2E1 is known to have a wide variation within human populations, primarily
due to enzyme induction in response to fasting, diabetes, or alcohol consumption (Kadlubar and Guengerich, 1992).
CYP2E1 activity can also be inhibited in vivo either by dietary intake of alcohol and chemicals such as diallyl sulphate
from garlic (Loizou and Crocker, 2001), or by pharmaceuticals such as chlormethiazole (Gebhardt et al., 1997) and
disulfaram (Kharasch et al., 1993).
Page 8 of 18
Draft Ethylbenzene HEAC Assessment/PEL Recommendation
Prepared by Julia Quint, Ph.D., HEAC Member
Initial Draft = 10/08; Revised draft = 10/09
§
Based on OEHHA 2008. In the current, draft Hot Spots risk assessment guidelines for deriving noncancer reference
exposure levels, the interspecies UF is increased from 3 to 6.
§§
Based on OSHA 1993. In the noncancer risk assessment for glycol ethers, OSHA applied an interspecies UF of 10.
Other Ethylbenzene Reproductive and Developmental Toxicity Studies
Saillenfait et al., 2007
J Appl. Toxicol 27 (2007); 32-42 Findings / Conclusions
Rat Inhalation Developmental A NOAEL of 250 ppm was identified in a developmental toxicity study by
Toxicity Study Saillenfait et al., 2007 when rats were administered ethylbenzene by
inhalation. Fetal toxicity limited to a reduction of fetal weight, and a reduction
NOAEL = 250 ppm of maternal weight gain were observed after treatment with 1000 ppm
ethylbenzene.
Methods
Three developmental experiments were carried out in this study. In the
experiment involving separate exposure to ethylbenzene, groups of 18 bred (15-18 pregnant) rats were exposed to vapors
of 250 ppm or 1000 ppm ethylbenzene 6 hours /day, on days 6-20 of gestation and compared to a control group exposed
concurrently to filtered room air in an adjacent chamber identical to those of the treatment groups. Females were observed
daily for clinical signs, before and after the exposure period. Maternal body weights were recorded on gestational day (GD)
6-13 and 13-21. The females were killed on GD 21. The uterus was then removed and weighed. The number of corpora
lutea, implantation sites, resorptions and dead and live fetuses were recorded. Uteri, which had no visible implantation
sites, were stained to detect very early resorptions. Live fetuses were weighed, sexed and examined for external anomalies.
Half of the live fetuses from each litter were examined for internal soft tissue changes, and the other half underwent skeletal
examination.
Results
No significant changes in maternal weight gain and corrected weight gain were observed after exposure to 250 ppm
ethylbenzene. At 1000 ppm ethylbenzene, these parameters were significantly different from controls. There was no effect
of treatment on the mean number of implantations and of live fetuses, and on the incidence of non-live implants and
resorptions. Fetal body weight was significantly decreased after exposure to 1000 ppm ethylbenzene. No increase in the
incidence of external and visceral variations was observed. There were no changes in the mean percentage of fetuses with
skeletal variations per litter or in the incidence of individual skeletal variations.
Discussion and Assessment
NOAELs of 250 ppm were obtained in two earlier ethylbenzene inhalation developmental toxicity studies published by this
group (Saillenfait et al., 2006 and Saillenfait et al., 2003).
PEL based on the NOAEL for developmental toxicity of ethylbenzene in this study (Saillenfait et al., 2007)
250 ppm (NOAEL) ÷ 3 (Interspecies UF ) ÷ 10 (Intraspecies**) = 8 ppm
§
250 ppm (NOAEL) ÷ 6 (Interspecies UF ) ÷ 10 (Intraspecies**) = 4 ppm
§§
250 ppm (NOAEL) ÷ 10 (Interspecies UF ) ÷ 10 (Intraspecies**) = 2.5 ppm
See page 8 for explanations of UFs.
Page 9 of 18
Draft Ethylbenzene HEAC Assessment/PEL Recommendation
Prepared by Julia Quint, Ph.D., HEAC Member
Initial Draft = 10/08; Revised draft = 10/09
Other Ethylbenzene Reproductive and Developmental Toxicity Studies (Continued)
Faber et al., 2006
Birth Defects Research (Part B) Findings / Conclusions
77:10-21 (2006)
A NOAEL of 500 ppm ethylbenzene was identified for F0 and F1
Two-Generation Rat Inhalation reproductive toxicity and offspring developmental endpoints in this two-
Reproduction Study generation reproduction inhalation study.
NOAEL = 500 ppm for reproductive
and developmental toxicity Methods
Four groups of male and female rats (F0 generation: 30/sex/group; F1
generation 25/sex/group) were exposed to either clean filtered air or
vapor atmospheres of ethylbenzene at 0, 25, 100 and 500 ppm
ethylbenzene for 6 hours daily for at least 70 consecutive days before
mating. Daily vaginal smears were carried out for assessment of estrous cyclicity, beginning 21 days before pairing.
Females were paired with males on a 1:1 basis for 14 days or until evidence of mating was observed. The F0 and F1 females
continued inhalation exposure throughout mating and gestation through gestational day (GD) 20. On lactation day (LD) 1-
4, the F0 and F1 females received corn oil or ethylbenzene via oral gavage at dose levels of 0, 26, 90, and 342 mg/kg/day
divided into three equal doses (0, 8.7, 30, and 114 mg/kg, respectively), approximately 2 hours apart at a dose volume of 1
ml/kg/dose (based on most recent body weights). The oral treatment was calculated to produce equivalent area-under-
concentrations (AUCs) for blood from a 6–hour inhalation exposure based on a physiologically-based pharmacokinetic
(PBPK) model (Tardif et al., 1997). Inhalation exposure of the F0 and F1 females was re-initiated on LD 5 and continued
through the day before euthanasia. Offspring were weaned on LD 21; inhalation exposure of F1 animals (two
weanlings/sex/litter, when possible) was initiated on postnatal day (PND) 22. Spermatogenic endpoints (sperm
concentrations, production rate, motility and morphology) were recorded for all F0 and F1 males. Ovarian primordial
follicle counts were recorded for all F1 females in the control and high exposure groups.
Results
Ethylbenzene exposure did not affect survival or clinical observations. Male rats in the 500 ppm group in both generations
gained weight more slowly than the controls. There were no indications of adverse effects on reproductive performance in
either generation. Male and female mating and lengths of estrous cycle and gestation, live litter size, pup weights,
developmental landmarks, and postnatal survival were unaffected. No adverse exposure-related macroscopic pathology
was noted at any level.
Discussion and Assessment
In a later study, Faber et al., 2007 reported NOAEL of 500 ppm for maternal reproductive toxicity, developmental toxicity,
and developmental neurotoxicity when rats were exposed by inhalation to 0, 25, 100, and 500 ppm ethylbenzene.
PEL based on the NOAEL for developmental toxicity of ethylbenzene in this study (Faber et al., 2006)
500 ppm (NOAEL) ÷ 3 (Interspecies UF ) ÷ 10 (Intraspecies**) = 17 ppm
§
500 ppm (NOAEL) ÷ 6 (Interspecies UF ) ÷ 10 (Intraspecies**) = 8 ppm
§§
500 ppm (NOAEL) ÷ 10 (Interspecies UF ) ÷ 10 (Intraspecies**) = 5 ppm
See page 8 for explanations of UFs.
Page 10 of 18
Draft Ethylbenzene HEAC Assessment/PEL Recommendation
Prepared by Julia Quint, Ph.D., HEAC Member
Initial Draft = 10/08; Revised draft = 10/09
Ethylbenzene Ototoxicity Study
Gagnaire et al., 2007
Arch Toxicol 81:127-143 Findings / Conclusions
A LOAEL of 200 ppm ethylbenzene was identified for ototoxic effects
Subchronic rat inhalation (moderate to severe losses in outer hair cells in the organ of Corti) in rats
ototoxicity study exposed by inhalation for 13 weeks to 200, 400, 600 and 800 ppm ethylbenzene..
Increased auditory thresholds were observed at 400, 600, and 800 ppm
LOAEL = 200 ppm for ethylbenzene.
moderate to severe losses of
outer hair cells Methods
Seventy rats (14 rats per concentration plus 14 controls) were exposed to
ethylbenzene 6 hours/day/week for 13 weeks. Solvent concentrations were
based on range-finding studies. The high concentration (800 ppm) was chosen
to produce a loss in body weight of less than 10% after 4 weeks of exposure.
The exposure period started 3-4 weeks after the electrodes were implanted. Each rat was allowed to recover from the
effects of the electrode implant surgery for at least 7 days before the electrophysiological recordings were started.
Brainstem auditory-evoked responses were used to determine thresholds at different frequencies. A quantitative
morphological study (histocochleogram) of the organ of Corti was used to assess hair cell losses. The solvent
concentrations in the exposure chambers were continuously monitored using gas-liquid chromatography.
Results
A dose-related, irreversible effect of ethylbenzene on outer hair cell (OHC) loss was observed in this study. Exposure to
800 and 600 ppm ethylbenzene in rats caused nearly complete hair loss in the three rows of the OHC in the organ of Corti.
Exposure to 400 ppm ethylbenzene also caused considerable losses--the highest losses were in the third row of the OHC.
Exposure to 200 ppm ethylbenzene caused significant losses (up to 30% in the mid frequency region) in the third row of the
OHC in four of eight animals. There were no significant hair losses in the controls. Ethylbenzene did not cause systemic
toxicity in the exposed animals. No exposure-related mortality was observed at any of the dose levels. There were no
statistically significant differences in body weight gain between controls and any of the exposed groups.
Audiometric thresholds were also higher in rats exposed to 800, 600, and 400 ppm ethylbenzene. However, this endpoint
was not as sensitive to the effects of ethylbenzene as the OHC. The highest hearing losses were observed in rats exposed to
600 and 800 ppm ethylbenzene. They ranged from 44 dB at 2 kHz to 49 dB at 16kHz. They did not increase significantly
throughout the exposure period. No recovery was observed 8 weeks after the end of the exposure. The hearing losses were
smaller in rats exposed to 400 ppm ethylbenzene. No shift in audiometric thresholds was observed in rats exposed to 200
ppm ethylbenzene or in the controls.
Discussion and Assessment
As discussed by Vyskocil et al. (2008), the results of this study are consistent with ethylbenzene-induced ototoxicity in rats
reported by others. Based on their review of the literature, Vyskocil et al. concluded that there is no evidence of either
ethylbenzene-induced hearing losses or ototoxic interaction after combined exposure to ethylbenzene and noise in workers.
However, since the rat appears to be the most appropriate model for studying the mechanism of toxicity of ethylbenzene
(ATSDR 2007), they recommend that ethylbenzene be considered as an ototoxic agent based on the animal evidence.
PEL based on LOAEL of 200 ppm for ototoxicity (outer hair cell loss) in Gagnaire et al. 2007
‡
200 ppm (study LOAEL) ÷ 10 (NOAEL ) ÷3 (Subchronic UF ) ÷ 3 (Interspecies UF) ÷ 3 (Intraspecies UF*) = 0.74 ppm
‡ §
200 ppm (study LOAEL) ÷ 10 (NOAEL ) ÷ 3 (Subchronic UF ) ÷ 6 (Interspecies UF ) ÷ 3 (Intraspecies UF*) = 0.4 ppm
‡ §§
200 ppm (study LOAEL) ÷ 10 (NOAEL )÷ 3 (Subchronic UF )÷ 10 (Interspecies UF ) ÷ 3 (Intraspecies UF*) = 0.2 ppm
Page 11 of 18
Draft Ethylbenzene HEAC Assessment/PEL Recommendation
Prepared by Julia Quint, Ph.D., HEAC Member
Initial Draft = 10/08; Revised draft = 10/09
*Based on potential differences in the ability of workers to metabolize ethylbenzene via the cytochrome P450 enzyme
CYP2E1(Sams et al., 2004). CYP2E1 is known to have a wide variation within human populations, primarily due to
enzyme induction in response to fasting, diabetes, or alcohol consumption (Kadlubar and Guengerich, 1992). CYP2E1
activity can also be inhibited in vivo either by dietary intake of alcohol and chemicals such as diallyl sulphate from garlic
(Loizou and Crocker, 2001), or by pharmaceuticals such as chlormethiazole (Gebhardt et al., 1997) and disulfaram
(Kharasch et al., 1993).
Application of intraspecies UFs in occupational health studies is also consistent with OSHA policy. OSHA (1989) states:
―…if the available data include a NOEL derived from a well-conducted human study, a smaller safety factor might be used
to establish an exposure limit than would be used if the data to be used to establish the limit consisted of a NOEL from an
animal study; in the latter case, there is greater uncertainty regarding the relationship between the animal NOEL and
human NOEL. Safety factors have also been used to recognize the fact that the human population is heterogeneous and
that there may be a wide variation in individual responses to toxic substances (the wide range in the odor thresholds
reported for some substances is a good illustration of individual variability in response).‖
‡
Based on OEHHA 2000a amd OEHHA 2007.
Based on OEHHA 2000a and OEHHA 2007.
§
Based on OEHHA 2008. In the current Hot Spots risk assessment guidelines for deriving noncancer reference exposure
levels, the interspecies UF is increased from 3 to 6.
Based on OEHHA 2000, OEHHA 2007, and OEHHA 2008. Exposure for 13 weeks or less (8 to 12% of a rat’s expected
lifetime) is designated as a subchronic exposure, and a 3-fold UF is used to adjust for chronic exposure.
§§
Based on OSHA 1993. In the noncancer risk assessment for glycol ethers, OSHA applied an interspecies UF of 10.
Summary of Derived PELs
Study Type Health LOAEL NOAEL UF (Total) PEL
Endpoint (ppm) (ppm) (ppm)
Bardodej and Bardodejova, Human Irritation 184 100 3 30
1961 intraspecies
Wolf et al., 1956 Rat Oral Liver & Kidney 596 200 10 20
3 interspecies;
3 intraspecies
Wolf et al., 1956 Rat Oral Liver & Kidney 596 200 18 11
6 interspecies;
3 interspecies
Wolf et al., 1956 Rat Oral Liver & Kidney 596 200 30 7
10 interspecies;
3 intraspecies
Mellert & Deckardt, 2007 Rat Oral Liver & Kidney 365 110 30 4
3 subchronic
3 interspecies
3 intraspecies
Mellert & Deckardt, 2007 Rat Oral Liver & Kidney 365 110 54 2
3 subchronic
6 interspecies
3 intraspecies
Mellert & Deckardt, 2007 Rat Oral Liver & Kidney 365 110 90 1
3 subchronic
10 interspecies
3 intraspecies
Page 12 of 18
Draft Ethylbenzene HEAC Assessment/PEL Recommendation
Prepared by Julia Quint, Ph.D., HEAC Member
Initial Draft = 10/08; Revised draft = 10/09
Study Type Health LOAEL NOAEL UF (Total) PEL
Endpoint (ppm) (ppm) (ppm)
NTP, 1999; OEHHA, 2007a Rat Cancer Not Unit Risk Not Applicable 0.5
Inhalation Applicable Value =
5 x 10-3
(mg/m3)-1
NTP, 1999 Rat Liver, Kidney, 250 75 10 7.5
Inhalation Pituitary Gland 3 interspecies
3 intraspecies
NTP, 1999 Rat Liver, Kidney, 250 75 18 4
Inhalation Pituitary Gland 6 interspecies
3 intraspecies
NTP, 1999 Rat Liver, Kidney, 250 75 30 2
Inhalation Pituitary Gland 10 interspecies
3 intraspecies
Andrew et al., 1981; Rat Developmental 1000 100 30 3
Hardin et al., 1981 Inhalation 3 interspecies
10 intraspecies
Andrew et al., 1981; Rat Developmental 1000 100 60 2
Hardin et al., 1981 Inhalation 6 interspecies
10 intraspecies
Andrew et al., 1981; Rat Developmental 1000 100 100 1
Hardin et al., 1981 Inhalation 10 interspecies
10 intraspecies
Saillenfait et al., 2007 Rat Developmental 1000 250 30 8
inhalation 3 interspecies
10 intraspecies
Saillenfait et al., 2007 Rat Developmental 1000 250 60 4
inhalation 6 interspecies
10 intraspecies
Saillenfait et al., 2007 Rat Developmental 1000 250 100 2
inhalation 10 interspecies
10 intraspecies
Faber et al., 2006 Rat Reproductive & None 500 30 17
inhalation Developmental 3 interspecies
10 intraspecies
Faber et al., 2006; Rat Reproductive & None 500 60 8
Faber et al., 2007 inhalation Developmental 6 interspecies
10 intraspecies
Faber et al., 2006; Rat Reproductive & None 500 100 5
Faber et al., 2007 inhalation Developmental 10 interspecies
10 intraspecies
Gagnaire et al., 2007 Rat Ototoxicity 200 None 270 0.74
inhalation 10 NOAEL or
3 subchronic 1
3 interspecies
3 intraspecies
Gagnaire et al., 2007 Rat Ototoxicity 200 None 540 0.4
inhalation 10 NOAEL
3 subchronic
6 interspecies
3 intraspecies
Page 13 of 18
Draft Ethylbenzene HEAC Assessment/PEL Recommendation
Prepared by Julia Quint, Ph.D., HEAC Member
Initial Draft = 10/08; Revised draft = 10/09
Study Type Health LOAEL NOAEL UF (Total) PEL
Endpoint (ppm) (ppm) (ppm)
Gagnaire et al., 2007 Rat Ototoxicity 200 None 900 0.2
inhalation 10 NOAEL
3 subchronic
10 interspecies
3 intraspecies
HEAC Ethylbenzene Health-Based Assessment and PEL Recommendation
A PEL of 0.5 ppm TWA is recommended to reduce the risk of cancer to 1 excess cancer case per 1000 workers exposed to
ethylbenzene over their working lifetimes. At the current ethylbenzene PEL of 100 ppm, the lifetime risk of cancer is 210
per 1000 exposed workers.
The PEL recommendation is based on a Unit Risk Value of 2.5 x 10-3 (mg/m3)-1 derived by Cal/EPA OEHHA and
approved by the Scientific Review Panel for Toxic Air Contaminants after public comment (OEHHA, 2007a). OEHHA’s
derivation is based on the incidence of kidney cancer in male rats in an NTP bioassay (NTP, 1999). As shown on page 6,
the recommended PEL of 0.5 ppm reflects adjustment of the ethylbenzene Unit Risk Value to account for the working
lifetime exposure of workers compared to lifetime exposure of the general public.
The HEAC PEL recommendation, which identifies ethylbenzene as an occupational carcinogen, is consistent with OSHA
regulation pertaining to the identification, classification, and regulation of carcinogens (29 Code of Federal Regulation,
Section 1990.143), and with the listing of ethylbenzene under Proposition 65 in 2004 as a chemical known to the State of
California to cause cancer. It is inconsistent, however, with the A3 notation, ―Confirmed Animal Carcinogen with
Unknown Relevance to Humans‖, assigned to ethylbenzene by the ACGIH based on their criteria. The use of quantitative
risk assessment to show the significance of the cancer risk at the existing PEL, and reduction of the cancer risk at the
recommended PEL, is consistent with the Supreme Court’s guidance in the Benzene Decision (Industrial Union
Department, AFL-CIO v. American Petroleum Institute, 448 U.S. 601, 655. (1980)). It is also consistent with the method
used to derive existing Cal/OSHA PELs for other carcinogenic substances such as methylene chloride, chromium VI,
formaldehyde, and ethylene oxide.
As shown in the PEL summary table (pages 12 and 13), in addition to reducing the risk of cancer, the recommended PEL of
0.5 ppm also protects against potential ethylbenzene-induced irritation, liver and kidney damage, and reproductive and
developmental damage. The extent to which the proposed PEL will protect against ethylbenzene-induced ototoxicity
depends on the magnitude of the uncertainty factors applied to the study LOAEL.
Production/Import & Facility Usage/Release Information
Major US Producers:
Chevron Phillips Chemical Company, Louisiana Cos-Mar Company, Louisiana The Dow Chemical Company,
Texas INEOS America, Texas Lyondell Chemical Company, Texas NOVA Chemical Corporation, Texas
Sterling Chemicals Incorporated, Texas Westlake Styrene Corporation, Louisiana
Source: SRI 2006. Available at: www.atsdr.cdc.gov/toxprofiles/tp110-c5.pdf
Page 14 of 18
Draft Ethylbenzene HEAC Assessment/PEL Recommendation
Prepared by Julia Quint, Ph.D., HEAC Member
Initial Draft = 10/08; Revised draft = 10/09
California industrial sectors (2-digit SIC) with 2002 reported total environmental releases (Scorecard 2007)
Rank Industrial Sector Ethylbenzene (Pounds)
1 Petroleum & Coal Products 30,359
2 Fabricated Metal Producta 9,527
3 Wholesale Trade—Nondurable Goods 8,546
4 Chemicals & Allied Producta 5,961
5 Transportation Equipment 4,500
6 Lumber & Wood Products 1,962
7 Primary Metal Industries 1,131
8 Business Services 11
9 Engineering & Management Services 8
Major California Facilities with Reported Total Environmental Releases in 2002 (Scorecard 2007)
(Total = 91 Ranked Facilities)
Rank Facility Ethylbenzene
(Pounds)
1 Shell Oil, Martinez Refinery 8,200
2 Chevron Prods. Co, Richmond Refinery 4,710
3 New United Motor Mfg., Inc., Fremont 4,500
4 Valero Refining Co. CA Benicia Refy. 4,100
5 Silgan Containers Mfg. Corp., Riverbank 3,198
6 Exxonmobil Oil Corp. Torrance Refy. 2,453
7 Armtec Defense Prods. Co., Coachella 2,323
8 Van Can Co., Fontana 2,150
9 Pacific MDF Prods. Inc., Rocklin 1,962
10 Conoco Phillips S.F. Refinery, Rodeo 1,800
11 Tesoro Refining & Marketing Co., 1,800
Martinez
12 Akzo Nobel Coating, Orange 1,658
Measurement Information
Air Monitoring
OSHA Occupational Safety and Health Guideline for Ethylbenzene
(http://www.osha.gov/SLTC/healthguidelines/ethylbenzene/recognition.html):
Determination of a worker's exposure to airborne ethyl benzene is made using a charcoal tube (100/50 mg sections, 20/40
mesh). Samples are collected at a maximum flow rate of 0.2 liter/minute (TWA or STEL) until a maximum collection
volume of 24 liters (TWA) is reached (3 liters for STEL sampling. The sample is then treated with 99:1 carbon
disulfide:dimethylformamide. Analysis is conducted by gas chromatography using a flame ionization detector (GC-FID).
This method is described in the OSHA Computerized Information System [OSHA 1994] and is fully validated. NIOSH
Method No. 1501 for aromatic hydrocarbons can also be used to determine a worker's airborne exposure to ethyl benzene.
This method is the reference method for the OSHA method described above and differs only in its use of carbon disulfide as
the solvent used to extract the sample (NIOSH 1994b).
Page 15 of 18
Draft Ethylbenzene HEAC Assessment/PEL Recommendation
Prepared by Julia Quint, Ph.D., HEAC Member
Initial Draft = 10/08; Revised draft = 10/09
Biological Monitoring
ACGIH Ethylbenzene Biological Exposure Index (BEI) Information
Determinant Sampling Time BEI Notation
Mandelic acid in urine End of shift at end of work week 1.5 g/g creatinine Ns (Nonspecific)
Ethylbenzene in end-exhaled air Sq (Seni-quantitative)
See ACGIH Ethylbenzene BEI Documentation (ACGIH 2001) for specific measurement information.
References Cited
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developmental neurotoxicity study of ethylbenzene in Crl-CD rats
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Initial Draft = 10/08; Revised draft = 10/09
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Initial Draft = 10/08; Revised draft = 10/09
Scorecard. 2007. Chemical profiles by facility. Ethylbenzene. Industrial sectors with reported total environmental
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(Accessed October 20, 2008)
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environmental releases in California. Available: http://www.scorecard.org/chemical-profiles/rank-industrial-
sectors.tcl?edf_chem_name=ETHYLBENZENE&edf_substance_id=100-41-
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F344/N rats and B6C3F1 mice (inhalation studies) (draft). Technical Report TR 466. NTP, Research Triangle Park, NC.
Vsykocil A, Leroux T, Truchon G, Lemay F, Gendron M Gagnon F, Majidi N E, and Viau C. Ethylbenzene should be
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Wolf MA, Rowe VK, McCollister DD, et al. 1956. Toxicological studies of certain alkylated benzenes and benzene. Arch
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