united States                         EXTERNAL REVIEW DRAFT
               Environmental Protection                   E CAO -CIN -U030
               Agencv	             December, 1987
»EPA       Research and
               Development
                  DRINKING WATER HEALTH ADVISORY FOR
                  1.3.5-TRIHETHYLBENZENE
              Prepared for
                  OFFICE OF DRINKING WATER
              Prepared by

              Environmental Criteria and  Assessment Office
              Office of Health and  Environmental Assessment
              U.S. Environmental Protection  Agency
              Cincinnati, OH  45268
                        DRAFT:  DO NOT CITE OR QUOTE
                                NOTICE
       ^     , document Is a preliminary draft.  It has not been formally released
       by the U.S.  Environmental Protection Agency and should not at thts stage be
       construed to represent Agency policy. It 1s being circulated for comments
       on Its technical accuracy and policy Implications.

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                                  DISCLAIMER


    This report  Is  an r-xternal  draft  for review purposes  only  and does not
constitute  Agency  policy.   Mention of  trade  names  or  commercial products
does not constitute endorsement or recommendation for use.
                                      11

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PREFACE
This Drinking Water Health Advisory was prepared for the Office of
Drinking Water by the Office of Health and Environmental Assessment,
Environmental Criteria and Assessment Office, Cincinnati, OH. These non—
regulatory Health Advisories derive 1—day, 10-day, longer—term and lifetime
health advisory levels for noncarcinogens, and carcinogenic potency values
for known carcinogens.
In the development of this Health Advisory, the scientific literature
has been Inventoried and key studies have been evaluated. Both the
published literature and Information obtained from Agency program offices
have been evaluated. The literature search is current through 1985. More
recent Information may have been added during the review process.
The first draft of this document was prepared by Syracuse Research
Corporation under EPA Contract No. 68-03—3228. This document was subse-
quently revised after reviews by staff within the Office of Health and
Environmental Assessment and the Office of Drinking Water, and outside
experts.
This Health Advisory will become part of the EPA drinking water docket.
iii

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i 3 ,S—Tr1methy1benzene -1- Decen er 22, 1987
I. INTRODUCTION
The Office of Drinking Water’s nonregulatory Health Advisory Program
provides Information on health effects, analytical methodology and treatment
technology that would be useful in dealing with contamination of drinking
water. Health Advisories also describe concentrations of contaminants in
drinking water at which adverse effects would not be anticipated to occur.
A margin of safety is Included to protect Sensitive members of the popu—
lat ion.
Health Advisories are not legally enforceable Federal standards.
They are subject to change as new and better information becomes available.
The Advisories are offered as technical guidance to assist Federal, State
and local officials responsible for protection of the public health when
emergency spills or contamination situations occur.
The Health Advisory numbers are developed from data that describe
noncarciriogenic endpoints of toxicity. They do not Incorporate quantita-
tively any potential carcinogenic risk from such exposure. For those chemi-
cals that are known or probable human carcinogens according to the proposed
Agency classification scheme, nonzero, 1—day, 10—day and longer—term Health
Advisories may be derived, with attendant caveats. Health Advisories for
lifetime exposures may not be recommended. For substances with a carcino-
genic potential, chemical concentration values are correlated with carcino-
genic risk estimates by employing a cancer potency (unit risk) value
together with assumptions for lifelong exposure and the ingestion of water.
The cancer unit risk Is usually derived from a linearized multistage model
with 95% upper confidence limits providing a low—dose estimate of cancer
risk. The cancer risk is characterized as being an upper limit estimate,
that is, the true risk to humans, while not identifiable, Is not likely to
exceed the upper limit estimate and in fact may be lower. While alternative
risk modeling approaches may be presented, for example One-hit, Welbull,
Logit or Probit, the range of risks described by using any of these models
has little biological significance unless data can be used to support the
selection of one model over another. In the Interest of consistency of
approach and in providing an upper-bound on the potential carcinogenic risk,
the Agency recommends using the linearized multistage model.
I

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1 ,3,5—Tr lmethylbenzene
—2—
February 16, 1988
II. GENERAL INFORMATION AND PROPERTIES
Uses
Mesitylene, sym—trimethylbenzene
CAS S
C14 3
Chemical formula
Molecular weight
Physical state (at 25°C)
Melting point
Boiling point
Vapor pressure (25°C)
Specific gravity (20°C)
Water solubility
Octanol/water partition
coefficient (log K )
Conversion factor
(25°C, 160 un Hg)
Taste threshold (water)
Odor threshold (water)
Odor threshold (air)
108-61-8
C 9 H 12
120.19
liquid
—52 .7°C
164.6°C
2.10 un Hg
0.865
97 mg/L
3.84
1 mg/m’-4.9l ppm
0.015 ppm
0.55 ppm
l, 3 .S—Trlmethylbenzene is used as a chemical Intermediate,
In anthraquinone vat dyes, and as an ultraviolet oxidation
stabilizer for plastics (Hawley, 1981).
Properties CH 3
Chemical Structure
0
6
CH
Hawley, 1981
Hawley, 1981
Patte et al., 1982
Verschueren, 1983
Amoore and Hautala, 1983
Hansch and Leo. 1985
Amoore and Hautala, 1983
Amoore and Hautala, 1983
I

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1,3 ,5-Trimethylbenzene .3_ October 22, 1987
Occurrence
a 1,3,5—Trimethylbenzene has been detected In Narragansett
Bay, RI, marine water (Wakeham et al., 1983). Trimethyl—
benzeni (isomer not specified) was detected (0.04 1 .ig/L) in
finished drinking waters from New Orleans and Miami (Keith
et al., 1916). It is likely that the occurrence of
l,3 ,5-trlmethylbenzene in water is due predominately to
petroleum (oil, gasoline) spills, seepage or runoffs, since
trimethylbenzene isomers are natural components of crude oil.
• l,3,5—Trimethylbenzene was detected at mean concentrations
of 0.38 and 0.40 ppb (0.011 and 0.008 mg/rn 3 ) In the air of
Los Angeles and Phoenix, respectively (Slngh et al., 1981).
In general, alkyl benzenes are recognized as atmospheric
contaminants derived mainly from car emissions.
Environmental Fate
• Henry’s Law Constants of 9.2x10 3 and 14.2x10 3
atm-m’/mol were calculated for l,3,5-trimethylbenzene in
distilled water and seawater, respectively (NAS, 1980).
These data suggest that volatilization of 1,3,5—trimethyl—
benzene from aqueous media Is rapid.
• Removal of l,3,5-trimethylbenzene In water from the
Narragansett Bay, RI, was estimated to be 220 hours In both
sunmier and winter (Wakeham et al., 1983). Volatilization
was considered to be the major removal process. Biodegra-
dation was expected to be important but data were not
reported.
• The half-life of 1,3,5-tr lmethylbenzene in Rhine River
surface water (Netherlands), based on monitoring data and
assuming a first-order process, was estimated to be 1 day
(Zoeteman et al.. 1980).
• Chemical degradation (hydrolysis, photolysis, oxidation) of
l,3 ,5—tr lmethylbenzene in water is not expected to be
significant (NAS. 1980; Wakeham et al., 1983; Jaber et al.,
1984).
• Waketiam et al. (1983) calculated a Narragansett Bay, RI
water/suspended particulate matter partition coefficient (74
cm 3 /g) for l,3,5-trlmethylbenzene that indicates a low
potential for sorption.

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l, 3 ,5-Trimethy lbenzene .4... Decenther 22, 1987
III. PHARMACOKINETICS
Abs orot ion
Alkylbenzenes In general are absorbed into the blood from
various portals of entry (Gerarde, 1959), with inhalation
and percutaneous absorption being the most important routes
of industrial exposures.
Distribution
• Gerarde (1959) reported that due to their high
lipophilicity, —85% of alkylbenzenes in blood are bound to
red blood cells. Alkylbenzenes generally distribute to
tissues with high lipid content.
Metabolism
• In general, alkylbenzenes are metabolized by side chain
oxidation to form alcohols or carboxylic acids. These
compounds are then conjugated with glucuronic acid or
glycine prior to urinary excretion. These reactions
probably occur primarily in liver microsomes (Gerarde, 1959).
• Mikuiski and Wlglusz (1975) found that an oral dose of 1200
mg/kg l. 3 ,S-trimethylbenzene given to male Wistar rats was
excreted In urine primarily as glycine conjugates (59—78% of
total dose) with lesser amounts of glucuronides and organic
sulfates (5—10% each). The principal metabolite was
3 .5—dimethylhippuric acid.
• Bakke and Scheline (1970) found that l,35-trlmethylbenzene
was not metabolized to phenolic compounds to a great extent
by rats. Only 0.4% of an oral dose of 100 mg/kg was
metabolized to 2,4,6—trimethyiphenol in 48 hours.
Excretion
• Gerarde (1959) reported that alkylbenzenes generally are
eliminated unchanged through the lungs or as biotransfor-
mation products in the urine. The metabolites (glycine and
glucuronide conjugates) are water soluble. A small amount
of the parent compound may be excreted in urine, but this is
1 imited by the low water solubility of the compound. The
amount eliminated in exhaled air depends on the
concentration in the blood and the vapor pressure.

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l , 3 1 5 —Trlmethylbenzene -5— Febr-Oary 16, 1988
Mikuiski and Wiglusz (1975) reported the following
elimination half—times for l.3 .5—tr lmethylbenzene
metabolites in male Wistar rats: glycine conjugates, 10.2
hours; glucuronides, 20.6 hours; and organic sulfates, 21.6
hours.
IV. HEALTH EFFECTS
Humans
Short—Term Exposure
• No data on short-term exposures to humans of
l , 3 ,5-trlmethylbenzene were located in the available
literature.
Longer—Term Exposure
• The only published report of human exposures (Baettig et
al., 1958) descrIbes an occupational health investigation of
27 painters working in a plant using the solvent Fleet-X DV
99. Chemical analysis of this solvent showed that it
consisted of 97.5% aromatic hydrocarbons and 2.5% of paraf—
finic and napthenlc hydrocarbons. Spectography identified
>50% of the solvent to be l,2,4—trimethyibenzene and >30% to
be l , 3 ,5—trlmethy lbenzene. Rough quantitatlon of the
exposure levels to the solvent, using indicator tubes for
benzene and its homologs, demonstrated air concentrations
between 10 and 60 ppm. If these vapors were ‘exclusively
trimethylbenzene, this would correspond to a concentration
range of 49-296 mg/rn 3 . Compared with 10 unexposed
unskilled workers as controls, clinical findings in the
exposed included subjective complaints of central nervous
system characteristics (vertigo, headaches, drowsiness),
chronic asthma—like bronchitis (classification criteria not
specified), hyperchromic anemia (<4.5 million erthrocytes/
2) and disturbances in blood clotting.
An ima is
Short—Term Exposure
• Gerarde (1959) reported that after absorption into the
blood, alkylbenzenes in general have two principal toxic
effects on tissue, irritation and injury of endothelial
tissue and central nervous system depression.
, ,

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1,3,5—Trimethylbenzene -6- Decen er 22, 1987
• Lazarew (1929) reported that atmospheric concentrations of
35-40 mg/t (34,480—44,332 mg/rn 3 ) caused loss of reflexes
and prostration in mice. The duration of these exposures
was not stated.
• Gerarde (1959) reported that a mixture of trimethylbenzene
isomers administered by gavage as 2.5 ml of a 1:1 v/v
solution in corn oil caused death of 1/10 rats (average
weight = 250 g). No other details were reported. Assuming
an average density of 0.89 g/mL for the mixture (Windholz,
1983), the average trimethylbenzene dosage was —4.4 g/kg.
• Pyykko (1980) orally administered 10 nmiol/kg/day (1202
mg/kg/day) 1,3,5-trimethylberizene in corn oil to 8—10 rats
for 3 -days. All rats survived and behaved normally, but
lost weight during the study. This was thought to be due to
fasting periods during the experiment; however, treated rats
lost significantly more weight than controls. They also
exhibited significantly increased liver weight and increased
cytochrome b 5 content in liver and kidney. 1,3,5-Tn—
methylbenzene also caused increased activity of various
microsornal enzymes in the liver, kidneys and lungs.
• Ungvary et al. (1981) administered 13.7 niiiol/kg/day (1647
mg/kg/day) l,3,5-trimethylbenzene orally to rats for 4
days. This resulted in an increase in hepatic cytochrome
P450 and cytochrome b 5 . Other parameters of toxicity were
not evaluated.
• Cameron et al. (1938) exposed 16 rats (sexnot specified) to
air saturated with l,3,5-trimethylbenzene (2240 ppm or
11,034 mg/rn 3 , assuming 760 nmi Hg at experimental
temperature of 20°C) for 24 hours. The animals exhibited
slowly developing narcosis and 4 died f 1 om respiratory
failure. The only remarkable pathology was congestion of
the lungs. No ill effects were noted in rats (n=lO) exposed
for 24 hours to 560 ppm (2158 mg/rn 3 , converted as
previously). Rats (n=lO) also tolerated with 560 ppm (2158
mg/ma) 8 hours/day for 14 days. Mice (n=lO) were also
unaffected by either a 24-hour exposure or a 14 days
exposure (8 hours/day) at 560 ppm (2758 mg/rn 9 ).
• Wiglusz et al. (1975a,b) exposed by inhalation groups of 5—8
male rats to 1,3,5—trimethylbenzene at 0, 1.5, 3.0 or 6.0
mg/L (0, 1500, 3000 or 6000 mg/rn 3 ) for 6 hours. Blood
samples were taken at intervals for 28 days. There was an
increase in the proportion of segmented neutrophilic
granulocytes, and a decrease in the proportion of lympho-
cytes, a day following exposure in the highest dose group.
which persisted 7—14 days. Serum alakline phosphatase (SAP)
was also increased in the 3 mg/L dose group.

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l, 3 .5—Trimethylbenzene -7- February 22, 1988
W1g1u z et al. (1975a,b) exposed male rats to 3 mg/I (3000
mg/rn 3 ) 6 hours/day, 6 days/week for 5 weeks. A “slight”
aiter ation in differential white blood cell (WBC) count and
elevated serum glutamic oxalacetic transaminase (SGOT) were
observed.
Longer-Term Exposure
• Bernshtein (1972) reported that inhalation of a trimethyl—
benzene mixture at 1 mg/I (1000 mg/m 3 ), 4 hours/day for 6
months, inhibited phagocytic activity of leukocytes in rats.
• Baettlg et al. (1958) exposed male rats (n=8) by inhalation
8 hours/day, 5 days/week to an approximate concentration of
1700 ppm of the solvent Fleet-X DV 99 (see chemical analysis
description under human longer-term exposure section) for 4
months. Rats (sex and number not specified) were also
exposed to 500 ppm of the solvent for 70 days. Assuming the
solvent content to be exclusively trimethylbenzene, these
exposures correspond to 8360 and 502 mg/rn 3 , respectively.
Differences between exposed rats and control were determined
for the following: motality, behavior, weight, drinking
water and food intakes, urine dilution and concentration
tests, urinary phenol excretion and red and white
differential blood cell counts. Four of the eight rats
exposed to 8360 mg/ma died within the first 2 weeks
whereas none died in the 502 mg/ma exposure group. Body
weight was decreased in both exposure groups but the effects
were confounded by a decrease In food intake. Severe
excitation with subsequent narcosis and ataxia toward the
end of the daily exposure period was exhibited in the high
exposure group but only indicated In the 502 mg/rn 3 group.
These phenomena receded within a few hours post exposure.
Increases in water intake, urinary diuresis and excretion of
free, total and bound phenol were noted in the exposed
rats. Blood analysis also revealed a relative lymphopenla
and neutrophilfa in the exposed rats. Histologic examina-
tion of the kidney, liver, spleen and lungs was performed
only on five animals (those that initially died were
replaced) of the high exposure group. Pathologic changes
Included: cloudy selling and fatty Infiltration in the
kidney, peripheral fatty Infiltration In the liver, and
Increase in secondary nodules In the spleen and marked
congestion of the pulmonary capillaries with alveolar wall
thickening.
Dermal/Ocular Effects
• Gerarde (1959) stated that direct skin contact with liquid
alkylbenzenes causes vasodilation, erythema and irritation.

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l. 3 5-Trimethylbenzene -8- December 22, 1987
Reproductive Toxicity
• Pertinent data regarding reproductive toxicity could not be
located in the available literature.
Developmental Toxicity
• Pertinent data regarding developmental toxicity could not be
located in the available literature.
utaQenic1 ty
• Pertinent data regarding mutagenicity could not be located
in the available literature.
Carcinogenicity
• Pertinent data regarding carcinogenicity could not be
located In the available literature. The NTP (1987) has not
selected this chemical for carcinogenicity testing.
V. QUANTIFICATION OF TOXICOLOGICAL EFFECTS
Health Advisories are based upon the identification of adverse health
effects associated with the most sensitive and meaningful noncarcinogenic
endpoint of toxicity. The induction of this effect is related to a particu-
lar exposure dose over a specified period of time, most often determined
from the results of an experimental animal study. Traditional risk charac-
terization methodology for threshold toxicants is applied in HA development.
The general formula is as follows:
(NOAEL OR LOAEL) (8W)
(OF(s)] (____ L/day) = ____mg/I ( ____ g/L)
where:.
NOAEL = No—Observed—Adverse...(ffect Level
(the exposure dose In mg/kg bu/day)
or
LOAEL = Lowest—Observed —Adverse...Effect Level
(the exposure dose in mg/kg bw/day)
OW = Assumed body weight of protected individual
(10 kg for child or 10 kg for adult)

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l . 3 ,5—Trimethy lbenzene -9- Febr-eary 16, 1988
Uf(s) = Uncertainty factors, based upon quality and nature
of data (10. 100, 1000 or 10,000 in accordance
with NAS/OOW or Agency guidelines)
— 1/day = Assumed water consumption
(1 L/day for child or 2 I/day for adult)
1-Day Health Advisory
In a 3-day oral experiment in rats, Pyykko (1980) observed body
weight loss compared with controls at 1202 mg/kg/day. Lower doses were not
tested. Ungvary et al. (1981) noted increased hepatic cytochrome P450 and
b 5 in rats treated with 1647 mg/kg/day by gavage for 4 days. Other para-
meters of toxicity were not evaluated. In single inhalation exposure
experiments, Cameron et al. (1938) noted narcosis and death In rats exposed
to 11,034 mg/rn 3 for 24 hours. No adverse effects were observed in rats
similarly exposed to 2158 mg/ma. Wlglusz et al. (l915a,b) observed
altered differential WBC counts In rats exposed to 6000 mg/ma for 6
hours. The biological significance of these findings Is unclear. Although
elevated SAP was observed at 3000 mg/ma, suggesting liver damage. It Is
not clear if SAP was measured in rats exposed to other concentrations of
l ,3 ,5—trlnjethylbenzene. No effects were noted after 6 hours exposure to
1500 mg/ma. Although the short-term exposure studies were not specific-
ally designed to determine a NOAEL, a provisional 1-day HA can be calculated
from the Pyykko (1980) ingestion study and from the Wlglusz (1975a)
inhalation study. In the Pyykko (1980) study a IOAEL can be defined as 1202
mg/kg/day. Using an uncertainty factor of 1000 to account for Interspecies
conversion, Individual variability and the use of a LOAEI:
1—day HA (child) = 1202 mg/kg/day x 10 kg = 12 mg/I
1000 x 1 L/day
where:
1202 mg/kg/day = LOAEI
10 kg = assumed body weight of a child
1000 = uncertainty factor used in accordance with
NAS/ODW or Agency guidelines in which a LOAEL
from an animal study is employed
1 1/day = assumed water consumption by a child
In the inhalation study (Wiglusz et al., 1975a), a NOAEL can be defined as a
6 hour exposure to 1500 mg/m 3 . An estimated absorbed dose (EAD) for the
rat can be calculated as:

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l , 3 5-Trimethylbenzene -10- Febniary 16, 1988
EAD = 1500 mg/rn 3 x 0.223 m 3 /day x 6/24 x 0.5 = 119 mg/kg/day
- 0.35 kg
where:
0.223 m 9 day = rat inhalation volume
0.35 kg = rat weight
6/24 = 6 hour exposure in one day
0.5 = assumed proportion of dose retained
If an uncertainty factor of 100 is used to account for interspecies conver-
sion and Individual variability:
1-day HA (child) = 119 mg/kg/day x 10 kg = 11.9 mg/I
100 x 1 L/day
where:
119 nm/kg/day = NOAEL
10 kg = rat weight
100 Uncertainty factor used in accordance with
NAS/ODW or Agency guidelines in which a NOAEL
from an animal study is employed
1 I/day = assumed water consumption by a child
The above studies give identical 1-day lAs and therefore:
1—day HA (child) = 12 mg/I
10—Day Health Advisory -
Oral data were not available from exposures of adequate dura-
tion. Cameron et al. (1938) observed no adverse effects on rats or mice
exposed by inhalation to 2758 mg/rn 3 , 8 hours/day for 14 days. Wiglusz et
al. (1975a,b) observed a Iislightu alteration In differential WBC counts and
elevated SGOT in rats exposed to 3000 mg/ni 3 , 6 hours/day, 6 days/week for
5 weeks. A provisional 10—day HA can be derived from the Cameron et al.
(1938) study when 8 hours/day inhalation 2758 mg/rn 3 can be defined as a
NOAEL in 14 days of exposure.

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l,35-Trimethythenzene -11- February 16, 1988
(AD — 2758 mg/rn 3 x 0.223 m 3 /day x 6/24 x 6/7 x 0.5
0.35 kg
(AD = 188 mg/kg/day
where:
0.223 m 3 day = rat Inhalation volume
0.35 kg = rat weight
0.5 assumed proportion of dose retained
6/24 = 6 hour exposure In one day
6/1 6 days per week
10-day HA (child) = 188 mg/kg/day x 10 kg 18.8 mg/I
100 x 1 1/day
where:
188 mg/kg/day = N0AEL
10 kg = assumed body weight of a child
100 Uncertainty factor chosen in accordance
with NAS/ODW or Agency guidelines In which
at NOEL or NOAEL from an animal study is
employed
1 I/day = assumed water consumption by a child
Longer—Term Health Advisory
Data were not sufficient for derivation of a longer—term HA.
Although significant results were Indicated in both the Bernshtein (1972)
and the Baettig et al. (1958) studies, the exposures were to mixtures of
trimethylbenzenes which makes quantitation of single components equivocal.
Additional deficits Include the lack of more than one exposure level and
detail (e.g. number of animals not specified, degree of inhalation not

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l.3.5-Trimethylbenzene —12- Febrlary 16, 1988
quantitated) in the Bernshtein 1972 study, The Baettlg et a]. (1958) animal
investigation lacked proper reporting of results (i.e. statistical analyses
either not done or not specified) and techniques, was not comprehensive in
scope (i.e. histologic exani nation performed on a limited number of animals
In the high exposure group only) and used small numbers of animals. The
human study also lacked quantification of symptoms/effects, was performed
on a small number and lacked appropriate follow—up.
Lifetime Health Advisory
The lifetime HA represents that portion of an individual’s total
exposure that is attributed to drinking water and Is considered protective
of noncarcinogenic adverse health effects over a lifetime exposure. The
lifetime HA is derived in a three step process. Step 1 determines the
Reference Dose (RfD), formerly called the Acceptable Daily Intake (ADI).
The RfD is an estimate (with uncertainty spanning perhaps an order of
magnitude) of a daily exposure to the human population (including sensitive
subgroups) that Is likely to be without appreciable risk of deleterious
health effects during a lifetime, and is derived from the NOAEL (or LOAEL),
identified from a chronic (or subchronic) study, divided by an uncertainty
factor(s) times an additional uncertainty factor. From the RfD, a Drinking
Water Equivalent Level (DWEL) can be determined (Step 2). A DWEL is a
medium—specific (i.e., drinking water) lifetime exposure level, assuming
100% exposure from that medium, at which adverse, noncarcinogenic health
effects would not be expected to occur. The DWEL is derived from the
multiplication of the RfD by the assumed body weight of an adult and divided
by the assumed daily water consumption of an adult. The lifetime HA Ir!
drinking water alone is determined in Step 3 by factoring in other sources
of exposure, the relative source contribution (RSC). The RSC from drinking
water is based on actual exposure data or. if data are not available, a
value of 20% Is assumed for synthetic organic chemicals and a value of 10%
Is assumed for Inorganic chemicals.
If the contaminant is classified as a known, possible or
probable carcinogen, according to the Agency’s classification scheme of
carcinogenic potential (U.S. EPA, 1986). then caution must be exercised in
making a decision on how to deal with possible lifetime exposure to this
substance. The risk manager must balance this assessment of carcinogenic
potential and the quality of the data against the likelihood of occurrence
and significance of health effects related to noncarcinogenic endpoints of
toxicity. In order to assist the risk manager in this process, drinking
water concentrations associated with estimated excess lifetime cancer risks
over the range of 1 in 10.000 to 1 in 1.000,000 for the 70 kg adult drinking
2 1 of water/day are provided in the Evaluation of Carcinogenic Potential
Section.
Data were not sufficient for derivation of a DWEL for the same
reasons specified for the longer-term HA.

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i. 3 . 5 -TrimethyThenzene -13- February 16, 1988
Evaluation of Carcinogenic Potential
Pertinent data regarding the carcinogen%city of l ,3.5—trlmethyl—
benzene could not be located in the available literature. The NIP (1987)
has not scheduled this chemical for carcinogenicity testing.
IARC has not evaluated the carcinogenic potential of 1,3,5—tn—
methylbenzene. Applying the criteria described in U.S. EPA (1986a) for
assessment of carcinogenic risk, l , 3 ,5-trimethylbenzene may be placed in
Group D: Not classified. This category signifies that available evidence
is insufficient to evaluate the agent’s carcinogenic potential.
VI. OTHER CRITERIA, GUIDANCE AND STANDARDS
ACGIH (1980, 1985) reconmiended a TLV of 25 ppm (—123 mg/rn 3 ) and a
STEL of 35 ppm (112 mg/rn 3 ) for l , 3 ,5-tr lmethyIbenzene. These values were
based primarily on human data for trimethylbenzenes (ACGIH, 1980).
VII. ANALYTICAL METHODS
Analysis of l, 3 , 5 —tr lmethyibenzene Is by a purge—and-trap gas
chromatographic procedure used for the determination of volatile aromatic
and unsaturated organic compounds in water (U.S. EPA, 1985a). This method
calls for the bubbling of an inert gas through the sample and trapping
volatile compounds on an adsorbent material. The adsorbent material is
heated to drive of I compounds onto a gas chromatographic column. The gas
chromatograph is temperature progranmed to separate the method analytes,
which are then detected by the photoionlzatlon detector. This method is
applicable to the measurement of l, 3 ,S-trimethylbenzene over a concentration
range of 0.03—1500 g/t. Confirmatory analysis Is by mass spectrometry
(U.S. EPA, l985b). The detection limited for confirmation by mass
spectrometry has not been determined.
VIII. TREATMENT TECHNOLOGIES
Very little information is available on treatment technologies
capable of removing l, 3 ,5—tnimethylbenzene from contaminated water.
U.S. EPA (1986b) estimated the feasibility of removing 1,3,5—tn-
methylbenzene from water by air stripping, employing the engineering design
procedure and cost model presented at the 1983 National ASCE Conference on
Environmental Engineering. Based on chemical and physical properties and
assumed operating conditIons, 90% removal efficiency of l,3,5-tnimethyl-
benzene was reported by a column with a diameter of 5.5 ft and packed with
12 ft of 1 inch plastic saddles. The air-to—water ratio required to achieve

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l ,35-Trimethylbenzene -14— febrUary 16, 1988
this degree of removal effectiveness Is 12. Actual system performance data,
however, are necessary to realistically determine the feasibility of
removing l,3,5-trimethylbenzene by air stripping from contamination drinking
water supplies.
Oxidation destruction of 1,3,5—trimethylbenzene might be a possible
treatment method. Hoigne and Bader (1983) determined rate constants of
reactions of ozone with non—Ionized solutes,. including substituted benzenes,
from the absolute rates with which ozone reacts in the presence of various
of these compounds in water. In the case of reactive solutes, the ratio of
reaction constants can be used to predict ozone selectively towards
different types of pollutants present in the same water source.
In sunvnary, the amenability of 1,3,5—trimethylbenzene to air
stripping has been clearly established. The application of oxidation needs
further investigation. Selection of individual or combination of techno-
logies to attempt l,3,5—trlmethylbenzene removal from contaminated drinking
water must be based on a case-by-case technical evaluation, and an assess-
ment of the economics involved.
IX. REFERENCES
ACGIH (American Conference of Governmental Industrial Hygienists). 1980.
Documentation of the Threshold Limit Values, 4th ed. Cincinnati, OH.
p. 415—416.
ACGIH (American Conference of Governmental Industrial Hygienists). 1985.
TLVs. Threshold Limit Values and Biological Exposure Indices for 1985—86.
Cincinnati. OH. p. 32.
Amoore, LE. and E. Hautala. 1983. Odor as an aid to chemical safety: Odor
thresholds compared with threshold limit values and volatilities for 214
industrial chemicals in air and water dilution. J. Appi. Toxicol. 3(6):
212-290.
Bakke, O.M. and R.R. Schellne. 1970. Hydroxylatlon of aromatic hydro-
carbons in the rat. Toxicol. Appi. Pharmacol. 16: 691—700.
Baettig, K.. E. Grand3ean. 1. Rossi and J. Rickenbacher. 1958.
Toxikologishe Untersuchungen Ueber TrimethylbenzoI. (Toxicological
Investigations of Trimethyl Benzene). Archly. Fuer Gewerbepathologles Und
Gewerbehyglene. 16:555—566. English translation available.
Bernshte ln, L.M. 1972. Phagocytosis reaction in experimental animals on
chronic poisoning by vapors of benzene and its methyl derivatives. Vop.
Gig. Tr. Profzabol., Mater. Nauch. Konf. 1971. 53—4 (Russ.) Edited by
Film, A.P. Kaz. Nauch.—Issled. Inst. Gig. Tr. Profzabol.: Karaganda. USSR.
Chem. Abstracts Vol. 81, 146520 p, 1974. (Cited in Sandmeyer. 1981) EnglIsh
abstract available.

-------
l , 3 ,5—Tr lmethy lbenzene -15- February 22, 1988
Cameron, G.R., J.L.H. Paterson, G.S.W. deSaram and J.C. Thomas. 1938. The
toxicity of some methyl derivatives of benzene with special reference to
pseudocumene and heavy coal tar naphtha. 3. Pathol. Bacteriol. 46: 95—107.
Gerarde, H.W. 1959. Toxicological studies on hydrocarbons, III. The blo—
chemmorphology of the phenylalkanes and phenylalkenes. Am. Med. Assoc.
Arch. md. Health. 19: 403-418.
Gerarde, H.W. 1960. No title provided. In: Toxicology and Biochemistry of
Aromatic Hydrocarbons. Elsevier Publishing Co. Amsterdam, London, New
York, Princeton. p. 188—189.
Hansch, C. and A.J. Leo. 1985. Medchem Project. Issue No. 26. Pomona,
College, Claremont, CA.
Hawley, G.G. 1981. The Condensed Chemical DIctionary., 10th ed. Van
Nostrand Reinhold Co., New York. p. 659.
Hoigne, 3. and H. Bader. 1983. Rate Constants of Reactions of Ozone with
Organic and Inorganic Compounds In Water-I. Non—Dissociating Organic
Compounds. Water Research. 17(2): 173-183.
Jaber, H.M., W.R. Mabey, A.T. Liu, T.W. Chou and H.L. Johnson. 1984. Data
acquisition for environmental transport and fate screening. SRI Inter-
national, Menlo Park, CA. p. 69. EPA 600/6-84/009. PB 84-243955.
Keith, L.H., A.W. Garrison, F.R. Allen, et a]. 1976. IdentificatIon of
organic compounds in drinking water from thirteen U.S. cities. •J : Identi-
fication and Analysis of Organic Pollutants in Water, L.H. Keith, Ed. Ann
Arbor Science, Ann Arbor, MI. p. 329-373.
Lazarew, N.W. 1929. Toxicity of various Hydrocarbon Vapors. Arch. Exptl.
Pathol. and Pharma., Naunyn—Schmiedebergs, 143:223. (Cited in Gerarde, 1960)
MIkuiski, P.1. and R. Wiglusz. 1975. The comparative metabolism of mesi-
tylene, pseudocumene, and hemimellitene In rats. Toxicol. Appi. Pharmacol.
31: 21—31.
NAS (National Academy of Sciences). 1980. The Alkyl Benzenes. National
Academy Press, Washington, DC. U.S. EPA Contract No. 68—01—4655.
NIP (National Toxicology Program) 1987. Toxicology Research and Testing
Program Management Status Report. 10/13/87. NIP, Research Triangle Park,
NC.
Patte, F., M. Etcheto and P. Laffort. 1982. Solubillty factors for 240
solutes and 207 stationary phases in gas—liquid chromatography. Anal. Chem.
54: 2239—2247.

-------
l , 3 1 5-Tr lniethy lbenzene —16-. February 16, 1988
Pyykko, K. 1980. Effects of methylbenzenes on microsomal enzymes in rat
liver, kidney and lung. Blochem. Blophys. Acta. 633: 1-9.
Sandmeyer, E.E. 1981. Aliphatic hydrocarbons. In: Patty’s Industrial
Hygiene and Toxicology, Vol. 2B, 3rd ed., G.D. Clayton and F.E. Clayton, Ed.
John Wiley and Sons Inc., New York. p. 3300-3302.
Singh, H.B., 1.J. Salas, AJ. Smith and H. ‘Shigeishi. 1981. Measurements
of some potentially -hazardous organic chemicals in urban environments.
Atoms. EnvIron. 15: 601-612.
Ungvary, G., S. Szebereny] and E. Tatral. 1981. The effect of benzene and
-its methyl derivatives on the MFO system. md. Environ. Xenobiotics, Proc.
mt. Conf. p. 285-292. (CA 97:1941636)
U.S. EPA. 1985a. U.S. EPA Method 503.1. Volatile Aromatic and Unsaturated
Organic Compounds In Water by Purge and Trap Gas Chromatography. Environ-
mental Monitoring and Support laboratory, Cincinnati, OH 45268, June 1985.
(Revised November 1985)
U.S. EPA. l985b. U.S. EPA Method 524.1, Volatile Organic Compounds in
Water by Purge and Trap Gas Chromatography/Mass Spectrometry, Environmental
Monitoring and Support Laboratory, Cincinnati, OH 45268, June 1985.
(Revised November 1985)
U.S. EPA. 1986a. Guidelines for Carcinogen Risk Assessment. Federal
Register. 51(185): 33992-34003.
U.S. EPA. 1986b. Economic Evaluation of l,3,5-Trimethylbenzene Removal
from Water by Packed Column Air Stripping. Prepared by Office of Water for
Health Advisory Treatment Summaries.
Verschueren, K. 1983. Handbook of Environmental Data on Organic Chemicals,
2nd ed. Van Nostrand Reinhold Co., New York. p. 812-813.
Wakeham, S.T., J.T. Goodwin and A.C. Davis. 1983. DistributIons and fate
of volatile organic compounds in Narragansett Bay, Rhode Island. Can. J.
Fish Aq. Sd. 40(Suppl. 2): 304-321.
Wiglusz, R., N. Kienitz, G. Delag. E. Galuszko and P. NikuIski. 1975a.
Peripheral blood of mesitylene vapor treated rats. Bull. Inst. Marit. Trop.
Med. Gdynia. 26(3-4): 315-322.
Wiglusz, R., G. Delag and P. Nikulskl. 1975b. Serum enzymes activity of
mesitylene vapor treated rats. Bull. Inst. Marit. Trop. Med. Gdynla.
26(3—4): 303—313. (CA 85:4.lllBp)
Windholz, N., Ed. 1983. The Merck Index, 10th ed. Merck and Co., Inc.,
Rahway, NJ. p. 5751

-------
l , 3 ,5—TrImethylbenzene -li- February 16, 1988
Zoeteman, B.C., K. Harmsen, J.B.H.J. Linders, C.F.H. Morra and W. Slooff.
1980. Persistent organic pollutants In river water and ground water of the
Netherlands. Chemosphere. 9: 231-249.
Zoetenian, B.C.J., E. De Greef and F.J.J. Brinkmann. 1981. Persistency of
organic contaminants in groundwater, lessons from soil pollution incidents
In the Netherlands. Sd. Total Environ. 21: 187-202.
Zuercher, F. and W. Glger. 1976. Volatile organic trace components in the
Glatt River. Vom Wasser. 41: 37—55. (Ger., Eng. SUlliflary)

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