March 31,  1987
                                     TOLUENE

                                  Health Advisory
                              Office  of Drinking Water
                        U.S.  Environmental Protection Agency
I.  INTRODUCTION

        The Health  Advisory  (HA)  Program,  sponsored  by  the Office of Drinking
   Water (ODW),  provides  information on the health effects, analytical method-
   ology and treatment technology that would be  useful  in dealing with the
   contamination of drinking water.   Health Advisories  describe nonregulatory
   concentrations of drinking water  contaminants at  which adverse health effects
   would not be anticipated  to  occur over  specific exposure durations.  Health
   Advisories contain  a margin  of safety  to protect  sensitive members of the
   population.

        Health Advisories serve as informal technical guidance to assist Federal,
   State and local  officials responsible  for protecting public health when
   emergency spills or contamination situations  occur.   They are not to be
   construed as legally enforceable  Federal standards.   The HAs are subject to
   change as new information becomes available.

        Health Advisories are developed for One-day, Ten-day, Longer-term
   (approximately 7 years, or 10% of an individual's lifetime) and Lifetime
   exposures based  on  data describing noncarcinogenic end points of toxicity.
   Health Advisories do not  quantitatively incorporate  any potential carcinogenic
   risk  from such exposure.   For those substances that  are known or probable
   human carcinogens,  according to the Agency classification scheme (Group A or
   B),  Lifetime HAs are not  recommended.   The chemical  concentration values for
   Group A or B carcinogens  are correlated with  carcinogenic risk estimates by
   employing a cancer  potency (unit  risk)  value  together with assumptions for
   lifetime exposure and  the consumption of drinking water.  The cancer unit
   risk  is usually  derived from the  linear multistage model with 95% upper
   confidence limits.   This  provides a low-dose  estimate of cancer risk to
   humans that is considered unlikely to pose a  carcinogenic risk in excess
   of the stated values.   Excess cancer risk estimates  may also be calculated
   using the One-hit,  Weibull,  Logit or Probit models.   There is no current
   understanding of the biological mechanisms involved  in cancer to suggest that
   any one of these models is able to predict risk more accurately than another.
   Because each  model  is  based  on differing assumptions,  the estimates that are
   derived can differ  by  several orders of magnitude.

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         This Health Advisory is based on information presented in the Office
    of Drinking Water's Health Effects Criteria Document (CD) for Toluene
    (U.S. EPA, 1985a).  The HA and CD formats are similar for easy reference.
    Individuals desiring further information on the toxicological data base or
    rationale for risk characterization should consult the CD.   The CD is available
    for review at each EPA Regional Office of Drinking Water counterpart (e.g.,
    Water Supply Branch or Drinking Water Branch),  or for a fee from the National
    Technical Information Service, U.S. Department of Commerce, 5285 Port Royal  Rd.,
    Springfield,  VA 22161, PB # 86-117975/REB.  The toll-free number is (800)
    336-4700; in the Washington, D.C. area: (703) 487-4650.
II. GENERAL INFORMATION AND PROPERTIES
    CAS No.   108-88-3
    Structural Formula
    Synonyms^

         0  Methylbenzene, phenylmethane,  toluol,  methylbenzol,  methacide

    Uses

         0  Raw material in the production of benzene and other organic solvents
            Solvent  (especially for paints, coatings, gums, oils and resins)
            Gasoline additive to elevate octane ratings

    Properties   (Amoore and Hautala, 1983; Cier, 1969; Sutton and Calder, 1975;
                 Tute, 1971; Weast, 1977;  Zoeteman et al., 1971)

            Chemical Formula                C7H8
            Molecular Weight                92.15
            Physical State (room temp.)     Clear, colorless liquid
            Melting  Point                   -94.9°C
            Boiling  Point                   110.6°C
            Vapor Pressure                  28.7 mm Hg at 25°C
            Specific Gravity                0.8623 at 15.6°C
            Water Solubility
                   Fresh Water              535 mg/L
                   Sea Water                379 mg/L
            Log  OctanoI/Water Partition     2.69
              Coefficient
            Taste Threshold (water)         0.04 mg/L; 1 mg/L
            Odor Threshold (water)          0.04 mg/L; 1 mg/L
            Odor Threshold (air)            0.6-140 mg/m3
            Conversion Factor               1 ppm =  3.77 mg/m3

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     Occurrence

          0  Toluene occurs naturally as a component of petroleum oil.

          0  Toluene is produced in large amounts (5.1 billion Ibs in 1981).
             Toluene also is produced indirectly in large volumes during gasoline
             refining and other operations.  Toluene content of gasoline can be as
             high as several percent.

          0  Releases of toluene to the environment are mainly to air due to toluene's
             volatile nature, with smaller amounts to water and soil.  Releases of
             toluene to water are due to spills and leaks of gasoline and other
             petroleum products and from the disposal of waste from paints,  inks
             and other products containing toluene.  Because of the widespread use
             of petroleum products, releases of toluene occur nationwide.

          0  Toluene degrades rapidly in air with a half life of a few days  (Mabey
             et al., 1981).  Toluene released to surface water rapidly volatilizes
             to air.  Toluene released to the ground binds somewhat to soil  and
             slowly migrates with ground water.  Toluene is biodegraded readily in
             soils and surface waters.  In the absence of biodegradation, toluene
             is expected to be stable in ground water (Marion and Malaney, 1963;
             Lutin et al.,  1965; Price et al., 1974; Bridie et al., 1979;
             Patterson and Kodukala, 1981; Tabak et al., 1981).

          0  Toluene occurs at low levels in drinking water, food and air.  Toluene
             occurs in both ground and surface public water supplies, with higher
             levels occurring in surface water supplies.  Based upon EPA's Ground
             Water Supply Survey (U.S. EPA, 1983), approximately 1% of all ground
             water-derived public drinking water systems have levels greater than
             0.5 ug/L.  The highest level reported in ground water was 1.4 ug/L.
             Based upon EPA's National Screening Program Survey, approximately 3%
             of all surface water-derived drinking water systems are contaminated
             at levels higher than 0.1 ug/L.  None of the systems were reported to
             contain levels higher than 1.4 ug/L.  Toluene is found in foods as a
             naturally occurring compound at ppb levels and in the air of urban
             and suburban areas at levels of approximately 10 ppb.  Toluene  has
             been reported to occur in indoor air at levels higher than outside.
             Based upon the available data, the major source of toluene exposure
             is from air.

III. PHARMACOKINETICS

     Absorption

          0  Studies in humans showed that toluene is absorbed quickly through the
             respiratory tract (Astrand et al., 1972; Astrand, 1975).  Toluene
             was detected in arterial blood within the first 10 seconds after
             exposure to 100 or 200 ppm toluene (Astrand et al., 1972).

          0  In humans,  inhalation exposure at 115 ppm (430 mg/m3) resulted  in a
             pulmonary absorption of 57% after 1 hour which decreased to a stable 37%
             of inspired dose after 2-4 hours of exposure (Nomiyama and Nomiyama,
             1974).

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     0  Absorption from  the GI-tract in male rats was  relatively rapid, with
        maximal blood-toluene  levels being reached within  2 hours after
        gastric intubation with 100 uL toluene in 400  uL peanut oil.   The oil
        may have slowed  absorption (Pyykko et al., 1977).

     0  Dermal absorption of aqueous toluene (180 to 600 mg/L) across  human hand
        skin was 160 to  600 ug/cm2/hour.  Absorption was related directly to
        concentration  (Dutkiewicz and Tyras, 1968a,b).

Distribution

     0  Little is known  about  the tissue distribution  of toluene in humans.
        Due to its lipophilic  nature and low water solubility, toluene would
        be expected to distribute to and accumulate in lipid  tissue (U.S.
        EPA, 1985a).

     0  In male rats,   tissue distribution of toluene and its metabolites is
        similar following inhalation of high concentrations of toluene (17,340
        mg/m3) or oral administration of a single dose of  labelled toluene
        (100 uL in 400 uL peanut oil) (Pyykko et al.,  1977; Bergman, 1979).
        Toluene is distributed throughout the body with greatest accumulation
        in lipid tissues (adipose, bone marrow).  Toluene  and its metabolites
        also were found  in relatively high concentration in tissues active in
        its metabolism and excretion (i.e., liver and  kidney).

Metabolism

     0  Toluene is metabolized in humans, rats and rabbits by side-chain
        hydroxylation  to benzyl alcohol, which is conjugated with glycine to
        form hippuric acid (70% of the dose) and then  excreted in the  urine
        (Daley et al., 1968; Ogata et al., 1970).

     0  In rats dosed orally with toluene, minor amounts of toluene undergo
        ring hydroxylation, probably via arene oxide intermediates, to form
        o-cresol and p-cresol  (0.04-1.0% of the dose)  which are excreted in
        the urine as sulphate  or glucuronide conjugates (Bakke and Scheline,
        1970; Angerer, 1979).
Excretion
        Following oral or inhalational exposure in both humans and animals,
        toluene is excreted rapidly as the unchanged compound in expired air
        and mainly as the metabolite, hippuric acid, in the urine (Smith
        et al., 1954; El Masri et al., 1956; Ogata et al.,  1970).

        Most of the urinary excretion of toluene occurs within 12 hours of
        the termination of exposure.  The concentration of  toluene in exhaled
        air of human subjects declined rapidly as soon as inhalation exposure
        was terminated (Astrand et al., 1972).

        The supply of glycine needed to conjugate with toluene in hippuric
        acid formation may be a limiting factor in the rate of toluene
        excretion.  Riihimaki (1979) suggested that toluene at 780 ppm  (2,940

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    Toluene
March 31, 1987
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            mg/m^) during  light  work  or  270  ppm  (1,010 mg/m^)  during heavy work
            would  saturate the capacity  for  glycine conjugation in humans.
IV.  HEALTH EFFECTS
    Humans
         0   Exposures  of humans  to  toluene  are  usually  the  result of  inhalation
            of toluene vapors in experimental or occupational settings or during
            episodes of intentional abuse.

         0   Acute  exposure  to toluene  at  approximately  200  ppm (754 mg/m^)  for
           - 8 hours  caused  symptoms indicating CNS toxicity (fatigue, headache,
        --  -nausea,  muscular  weakness,  confusion and  incoordination (von Oettingen
            et al.,  1942a,b;  Carpenter et al.,  1944).  These effects  generally
            increased  in severity with increases in toluene concentration (von
            Oettingen  et al., 1942a,b).  Toluene vapor  at 100 ppm for 8-hour
            exposures  appeared  to be the  NOAEL  for these  effects  (von Oettingen
            et al.,  1?42a,b).

         0   Subacute occupational exposure  to toluene (for  1  to 3 weeks)  at
            levels of  50 to 1500 ppm (189 to  5660 mg/m^)  resulted in  symptoms
            similar  to those  seen in acute  exposure studies and which were related
            to level of exposure (Wilson, 1943).

         0   Chronic  exposure  to toluene vapors  at levels  of approximately 200
            to 800 ppm have been, associated primarily with  CNS (von Oettingen
            et al.,  1942a,b)  and, possibly, peripheral  nervous system effects
            (Matsushita et al.,  1975;  Seppalainen et  al.,  1978).   Disturbances in
            memory,  thinking, psychomotor skills, visual  accuracy and sensorimotor
            speed  were reported  in  a significant number of  workers exposed  to 200
            to 800 ppm for  "many years" (Munchinger,  1964).  Hanninen et al.
            (1976) reported many differences  in performance test  results  between
            non-exposed workers and painters  exposed  to approximately 30.6 ppm
            toluene  for an average  of  14.8  years.  Effects  indicative of  cerebral
            and cerebellar dysfunction, such  as ataxia, tremors,  equilibrium
            disorders, impaired  speech, vision  and hearing,  and impaired  memory
            and coordination  have been reported in chronic  abusers of toluene
            (Knox  and  Nelson,  1966;  Boor  and  Hurtig,  1977;  Sasa et al.,  1978).

         0   Chronic  abuse  of  and occupational exposures to toluene (approximately
            200 to 800 ppm) for  periods ranging from  2  weeks to 6 years  have been
            associated with hepatomegaly and  hepatic  function changes (Greenburg
            et al.,  1942; Grabski,  1961).  Renal function also appears to be
            affected in chronic abusers of  toluene (Kroeger et al., 1980; Moss
            et al.,  1980).
    Animals
    Short-term Exposure
            The oral toxicity  of  toluene is  relatively low,  with an LDsg between
            6.4 and 7.53  g/k
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        1969; Kimura et al., 1971).  The earliest observable sign of acute
        oral toluene toxicity in adult rats is inhibition of the functions
        of the CNS, which become evident at approximately 2.0 g/kg (Kimura
        et al., 1971 ).

     0  The LCcg for inhaled toluene is 4,618 ppm (17,400 mg/m3) after a
        6-hour exposure in rats (Bonnet et al.,  1982).   No effects were
        reported after acute exposures to 620 or 1,100 ppm (2,340 or 4,150
        mg/m3) toluene, but 1250 ppm (4710 mg/m3) affected coordination and
        irritated the mucous membranes in rats.

     0  The dermal LD5Q in rabbits is 12.2 gAg  (Smyth  et al.,  1969).

Long-term Exposure

     0  Subchronic oral administration of toluene to female rats at 118,  354
        or 590 mgAg/day for 193 days (5 days/week for  138 total doses)
        resulted in no effects at any level (hematological, clinical,  gross
        or histopathological) and a NOAEL >590 mg/kg/day (Wolf et al., 1956).

     0  Subchronic inhalation of toluene for 6 weeks resulted in slight
        pulmonary irritation in rats exposed at 200 ppm (754 mg/m3) for 7
        hours/day, 5 days/week (von Oettingen et al., 1942a).  Renal effects
        were evident in rats treated at 600 ppm (2260 mg/m3) for 7 hours/day,
        5 days/week for 6 weeks.

     0  Chronic inhalation of toluene was studied in F344 rats exposed to 30,
        100 or 300 ppm (113, 377 or 1,130 mg/m3) toluene 6 hr/day, 5 days/week
        for 24 months  (CUT, 1980).  Reduced hematocrit values were reported
        in females exposed to 100 and 300 ppm.  Increased corpuscular hemoglobin
        concentration  was reported in females exposed to 300 ppm.

Reproductive Effects

     0  Data regarding the reproductive effects of toluene have not been
        located.

Developmental Effects

     0  Based on data reported in an abstract, oral administration of 1.0 mL/kg
        toluene in cottonseed oil to pregnant CD-1 mice, 3 times daily on
        days 6 through 15 of gestation, resulted in a statistically signifi-
        cant increase in the incidence of cleft palate (Nawrot and Staples,
        1979).  Maternal toxicity was not seen after exposure to toluene  but
        a significant increase in embryonic lethality occurred at doses of
        0.3 ml/kg and up.

     0  Inhalation exposures to 1,000 mg/m3 by pregnant rats for 8 hours  per
        day on gestational days 1 through 21 resulted in a significant increase
        in signs of skeletal retardation but did not cause internal or external
        malformations  (Hudak and Ungvary, 1978).

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   Mutagenicifcy
        0  Toluene has  been tested  for mutagenicity by many investigators using
           various assay methods (reverse mutation, mitotic gene conversion and
           mitotic crossing-over) and has not been demonstrated to be genotoxic
           or mutagenic.

   Carcinogenici ty

        0  CUT (1980)  concluded that exposures to 0,  30, 100 or 300 ppm toluene
           for 24 months did not produce an increased incidence of neoplastic,
           proliferative,  inflammatory or degenerative lesions in F344 rats.
           However,  the highest dose used did not approach the Maximum Tolerated
           Dose (MTD) and,  therefore,  it has been suggested that toluene may  not
           have been adequately tested for carcinogenicity (Powers, 1979).

        0  Other  studies suggest that toluene is not carcinogenic when applied
           topically (twice weekly  applications of 0.1 ml toluene for 20 weeks)
           to the shaved skin of mice (Frei and Stephens, 1968).

        0  No evidence  of a promotion effect was noted when toluene (0.1 ml)
           was painted  on the skin  of mice twice weekly for 20 weeks following
           initiation with 7,12-dimethyl-benz(a)anthracene (Frei and Kingsley,
           1968;  Frei and Stephens,  1968).

        0  Toluene is used extensively as a solvent for lipophilic chemicals
           being  tested for carcinogenic potential.  Negative control studies
           employing 100% toluene were negative.

V. QUANTIFICATION OF TOXICOLQGICAL  EFFECTS

        Health Advisories (HAs)  are  generally determined for One-day,  Ten-day,
   Longer-term (approximately 7 years) and Lifetime exposures if adequate data
   are available  that identify a sensitive noncarcinogenic end point of toxicity.
   The HAs for noncarcinogenic toxicants are derived using the following formula:

                 HA = (NOAEL or LOAEL) x (BW) = 	 mg/L (	 ug/L)
                        (UP) x (    L/day)
   where:
           NOAEL or LOAEL =  No- or  Lowest-Observed-Adverse-Effect-Level
                            in mg/kg bw/day.

                       BW =  assumed body weight of a child (10 kg)  or
                            an adult (70 kg).

                       UF =  uncertainty factor (10,  100 or 1,000),  in
                            accordance with NAS/ODW guidelines.

                	 L/day =  assumed daily water consumption of a child
                            (1 L/day) or an adult (2 L/day).

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One-day Health Advisory

     The effects of single inhalation exposures of humans to toluene for
periods up to 8 hours have been reported by several investigators (von
Oettingen et al., 1942a,b; Carpenter et al., 1944; Ogata et al.,  1970;
Gamberale and Hultengren, 1972).  Based on the consistent dose-response data
from a combination of these studies, it is evident that toluene at approxi-
mately 100 ppm for up to 8 hours/day causes no apparent adverse effects in
humans.  Complaints of headache and drowsiness were reported by one volunteer
exposed to 50 and 100 ppm, while consistent toluene-induced effects (fatigue,
muscular weakness, incoordination) were evident in persons exposed to 200 ppm
for 8 hours.  Gamberale and Hultengren (1972)  reported that a 20-minute
exposure to 100 ppm toluene was a no-effect level when determined by perceptual
speed and reaction time tests.  At 200 ppm, toluene was noted as  clearly
causing toxic effects such as incoordination,  exhilaration and prolonged
reaction time (von Oettingen et al., 1942a,b;  Carpenter et al., 1944; Ogata
et al., 1970).  These data substantiate the selection of 100 ppm  (377 mg/m3)
toluene as the NOAEL in humans exposed for up to 8 hours.

     Using a NOAEL of 100 ppm (377 mg/m3), a One-day HA is calculated as
follows:

Step 1:  Determination of the Total Absorbed Dose (TAD)

        TAD = (377 mg/m3)(20 m3/day)(0.6)(8 hr/24 hr) = 21>5 mg/kg/day
                               / u &cf

where:

               377 mg/m3 = NOAEL (converted from 100 ppm) for absence of
                           toxic effects in humans (von Oettingen et al.,
                           1942a,b).

        8 hours/24 hours = duration of exposure in one day.

               20 m3/day = assumed daily ventilation volume for 70 kg adult

                     0.6 = estimated ratio of dose absorbed (Nomiyama and
                           Nomiyama, 1974).

                  70 kg = assumed body weight of an adult.

Step 2:

     The One-day HA for a 10-kg child is derived from the TAD as  follows:

        One-day HA = (21.5 mg/kg/day)(10 kg) = 21.5 mg/L (21,500  ug/L)
                         (10) (1 L/day)

where:

        21.5 mgAg/day = TAD

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                 10 kg = assumed body weight of a child.

                    10 = uncertainty factor, chosen in accordance with NAS/ODW
                         guidelines for use with a NOAEL from a human study.

               1 L/day = assumed daily water consumption of a child.

Ten-day Health Advisory

     No information was found in the available literature that was suitable
for determination of a Ten-day HA value.  It is therefore recommended that
the DWEL,  adjusted  for a 10 kg child (3.46 mg/L), be used at this time as a
conservative estimate of the Ten-day HA value.

Longer-term Health  Advisory

     No information was found in the available literature that was suitable
for determination of the Longer-term HA values.  It is therefore recommended
that the DWEL, adjusted for a 10 kg child (3.46 mg/L), be used at this time
as a conservative estimate of the Longer-term HA values.

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 noncar-
cinogenic 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 esti-
mate of a daily exposure to the human population that is likely to be without
appreciable risk of deleterious  effects over a lifetime, and is derived from
the NOAEL (or LOAEL), identified from a chronic (or subchronic) study, divided
by an uncertainty factor(s).  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 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
Group A or B carcinogen, according to the Agency's classification scheme of
carcinogenic potential (U.S. EPA, 1986), then caution should be exercised in
assessing the risks associated with lifetime exposure to this chemical.

     The study by CUT (1980) is the most appropriate from which to derive
the Lifetime Health Advisory.  Rats were exposed to toluene via inhalation at
0, 113, 337 or 1130 mg/m3 for 6 hrs/day 5 days/wk for two years.  All parameters
measured at the end of the study, to include clinical chemistry, hematology
and urinalysis, were normal with the exception of a decreased hematocrit in
females exposed at  100 and 300 ppm (377 and 1130 mg/m3, respectively) and an
increased corpuscular hemoglobin concentration in the high-dosed females.

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'Similar changes did riot occur in the males nor were they related  to any patho-,
logical findings.  From these results, a NOAEL of 300 ppm  (1130 mg/kg) was
identified.

     Using this NOAEL, the Lifetime Health Advisory is derived as follows:


Step 1:  Determination of  the Total Absorbed Dose (TAD)

TAD =  (113° mg/rc3) (6 hours/24 hours)  (20 m3/day) (5/7)  (0.6) = 34.6 mg/]cg/day
                               70 kg

where:

              1130 mg/m3 = NOAEL from animal data.

        6 hours/24 hours = exposure duration in one day.

               20 m3/day = assumed daily respiratory volume of an adult.

                     5/7 = conversion of 5 day/week dosing regimen to 7 day/week
                           continuous exposure.

                     0.6 = estimated ratio of dose absorbed (Nomiyama and
                           Nomiyama, 1974).

                   70 kg = assumed body weight of an adult.


Step 2:  Determination of  the Reference Dose (RfD)

                   RfD =  (34.6 mg/kg/day) = Q.346 mg/kg/day
                               100

Where:

        28.8 mgAg/day = TAD.

                   100 = uncertainty factor, chosen in accordance with NAS/ODW
                         guidelines for use with a NOAEL from an  animal study.


Step 3:  Determination of  the Drinking Water Equivalent  Level (DWEL)

          DWEL =  (0.346 mg/kg/day) (70 kg) = 12.-| mg/L (12,100 ug/L)
                          (2 L/day)

where:

        0.346 mg/kg/day =  RfD.

                   70 kg =  assumed body weight of an adult.

                 2  L/day =  assumed daily water consumption  of an adult.

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    Step 4:  Determination of the Lifetime Health Advisory

               Lifetime  HA = (12.1  mg/L)  (20%)  = 2.42  mg/L (2,420 ug/L)

    where:

            12.1  mg/L =  DWEL.

                  20% =  assumed  relative  source contribution from water.

    Evaluation of Carcinogenic Potential

         0   IARC (1982)  has not  classified toluene into various  categories of
            carcinogenic risk to humans.

         0   Applying the criteria described in  EPA's guidelines  for assessment of
            carcinogenic risk (U.S. EPA,  1986), toluene may be classified in
            Group D:  Not classified.   This category is for agents with inadequate
            animal evidence of carcinogenicity.

         0   The chronic  (106-week)  bioassay of  toluene in F-344  rats of both
            sexes resulted in no carcinogenic effects  (CUT, 1980).  Gross and
            microscopic  examination of  tissues  and organs revealed no increase
            in neoplastic tissue or tumor masses among rats treated at 30, 100 or
            300 ppm when compared with  controls.  This bioassay,  however,  could
            have been performed  at higher exposure levels, since the highest dose
            administered (300 ppm)  was  not a Maximum Tolerated Dose (MTD).

         0   Prechronic carcinogenicity  testing  of commercial toluene administered
            by gavage to F344 rats  and  B6C3F-J mice has been conducted,  but a
            technical report on  the data  has not been  issued (NCI, 1983).   The NTP
            (NCI, 1983)  also has started  a chronic bioassay of commercial toluene
            in rats and  mice exposed by inhalation. Testing is  in progress, but
            neither preliminary  nor final data  are available.  The assessment of
            the carcinogenic potential  of toluene must await the completion of
            these tests.


VI. OTHER CRITERIA,  GUIDANCE AND STANDARDS

         0   TLV = 100 ppm (   375 mg/m3);  STEL  = 150 ppm (   560 mg/m)3 for skin
            (ACGIH, 1981).

         0   EPA's ambient water  quality criterion for  toluene is 14.3 mg/L (U.S.
            EPA,  1980).

         0   The EPA has  proposed a Recommended  Maximum Contaminant Level (RMCL)
            of 2.0 mg/L  based upon the  Adjusted Acceptable Daily Intake (AADI) of
            10.1  mg/L for noncarcinogenic effects assuming 20% contribution from
            drinking water (U.S. EPA,  1985d).

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 VII. ANALYTICAL METHODS

           0  Analysis of  toluene is by a purge-and-trap gas chromatographic procedu^J
              used for the determination of volatile aromatic and unsaturated organic
              compounds in water (U.S.  EPA, 1985b).  This method calls for the
              bubbling of an inert gas through the sample and trapping  toluene on an
              adsorbant material.  The adsorbant material is heated to drive off
              toluene onto a gas chromatographic column.  The gas chromatograph is
              temperature programmed to separate the method analytes which are then
              detected by  the photoionization detector.  This method is applicable to
              the measurement of toluene over a concentration range of 0.02 to 1500
              ug/L.  Confirmatory analysis for toluene is by mass spectrometry (U.S.
              EPA, 1985c).  The detection limit for confirmation by mass spectrometry
              is 0.2 ug/L.

VIII. TREATMENT TECHNOLOGIES

           0  Treatment options for removing toluene from drinking water sources
              include aeration and adsorption onto granular activated carbon (GAC).
              Conventional treatment methods have been found to be ineffective for
              the removal of toluene from drinking water (ESE, 1982).

           0  The Henry's Law Constant for toluene (288 atm at 20°C) indicates it
              is amenable  to removal by aeration.  In a pilot-scale study, a packed
              column aerator, operated at 50 to 90% of its flooded condition,
              removed toluene from contaminated water (ESE, 1982).  A field study
              by Cummins (1985) also demonstrated the efficacy of aeration treatment.

              Water containing 62 ug/L toluene from a gasoline spill was decontami-
              nated successfully by air stripping (air to water ration was 30:1 or
              greater).  The process was less effective at lower air to water
              ratios (i.e., 8:1) but even at this ratio about 70% of the toluene
              was removed.

           0  Air stripping is an effective, simple and relatively inexpensive process
              for removing toluene and other volatile organics from water.  However,
              use of this process then transfers the contaminant directly  to the
              air stream.  When considering use of air stripping as a treatment
              process,  it is suggested that careful consideration be given to the
              overall environmental occurrence, fate, route of exposure and various
              hazards associated with the chemical.

           0  Carbon adsorption isotherms developed by Dobbs and Cohen  (1980) showed
              that GAC can remove toluene from water effectively.  However, with
              Freundlich constants of 26 for K and 0.44 for 1/n, carbon usage rates
              would be relatively high (U.S. EPA, 1985b).  Toluene was also success-
              fully removed from a light hydrocarbon cracking quench using GAC.
              The solution treated contained 8.3 mg/L toluene.  Breakthrough on a 6
              ft x 4 inch GAC column (Filtrasorb® 300) occurred after the processing
              of about 1,200 gallons.  Suffet et al., as cited by ESE (1982) found
              that GAC (Filtrasorb® 400) adsorbed toluene from water containing a
              mixture of contaminants.  However, in this pilot study, breakthrough
              occurred after 10 weeks, whereas levels of the other contaminants
              remained below detection for 18 weeks.

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                                         -13-


IX.  REFERENCES

    ACGIH.   1984.   American  Conference  of  Governmental  Industrial  Hygienists.
         Toluene.   Documentation  of  threshold  limit values  for substances  in
         workroom  air.   3rd  ed.   Cincinnati, OH.  p.  400.

    Amoore,  J.E.,  and E. Hautala.  1983.   Odor as an aid to chemical safety:
         Odor  threshold  compared  with  threshold limit values  and volatilities  for
         214 industrial  chemicals in air  and water  dilution.   J. Appl.  Tox.
         3:272-290.

    Angerer, J.  1979.   Occupational chronic exposure to organic solvents.   VII.
         Metabolism of  toluene in man.   Int. Arch.  Occup.  Environ. Health.  43(1):
         63-67.

    Astrand, I.  1975.   Uptake of solvents  in  the blood and tissues  of  man.  A
         review.   Scand. J.  Work  Environ.  Health.   1(4):199-218.

    Astrand, I., H. Ehrner-Samuel, A. Kilbom and P.  Ovrum.   1972.   Toluene
         exposure.  I.   Concentration  in  alveolar air and  blood at rest and
         during exercise.  Work Environ.  Health.  72(3):119-130.

    Bakke,  O.K., and R.R.  Scheline.   1970.   Hydroxylation  of  aromatic hydrocarbons
         in  the rat.  Toxicol. Appl. Pharmacol.  16:691-700.

    Bergman, K.   1979.   Whole-body autoradiography  and  applied tracer techniques
         in  distribution and elimination  studies of  some organic solvents.
         Benzene,  toluene, xylene, styrene, methylene chloride,  chloroform,  carbon
         tetrachloride and trichloroethylene.  Scand. J. Work  Environ.  Health.
         5:  Suppl. 1.  (263 pp.).

    Bonnet, P., Y. Morele, G. Raoult, D.  Zissu and D. Gradiski.  1982.   Determi-
         nation of the median lethal concentration  of the  main aromatic hydrocarbons
         in  the rats.  Arch.  Mai. Prof. Med. Trav.  Secur.  Soc.   43(4):261-265.

    Boor,  J.W., and H.I. Hurtig.   1977.   Persistent cerebellar ataxia after
         exposure  to toluene.  Ann.  Neurol.  2(5):440-442.

    Bridie,  A.L.,  e_t al.  1979.   BOD and  COD of some photochemicals.  Water
         Research.  13:627-630.

    Carpenter, C.P.,  C.B. Shaffer, C.S. Weil and H.F. Smyth, Jr.   1944.  Studies
         on  the inhalation of 2,3-butadiene; with a comparison of  its narcotic
         effect with benzol,  toluol  and styrene, and a  note on the elimination of
         styrene by the  human.  J. Ind. Hyg. Toxicol.  26:69-78.

    CUT.   1980.   Chemical Industry  Institute  of Toxicology.   A twenty-four  month
         inhalation toxicology study in Fischer-344 rats exposed to atmospheric
         toluene.   Executive Summary arid  Data  Tables.   October 15,  1980.

    Cier,  H.E.   1969. Toluene.   In;  Kirk-Othmer Encyclopedia of  Chemical Tech-
         nology, Vol.  20,  2nd ed., A.  Standen, ed.   John Wiley and Sons, Inc.,
         N.Y., p.  528.

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                                     -14-
Cummins, M.D.' 1985.  Field evaluation of packed column air stripping.  U.S.
     Environmental Protection .Agency, Office of Drinking Water, Technical
     Support Division, Cincinnati, Ohio 45268.

Daley, J., D. Jerina and B. Witkop.  1968.  Migration of deuterium drinking
     hydroxylation of aromatic substrates by liver microsomes.  I.  Influence
     of ring substituents .  Arch. Biochem. Biophys.  128(2):51 7-527.

Dobbs, R.A., and J.M. Cohen.  1980.  Carbon adsorption isotherms for toxic
     organics.  EPA 600/8-80-023.  MERL, U.S. EPA, Cincinnati, Ohio.

Dutkiewicz, T., and H. Tyras.  1968a.  The quantitative estimation of toluene
     skin absorption in man.  Arch. Gewerbepath Gewerbehyg.  24:253-257.

Dutkiewicz, T., and H. Tyras.  1968b.  Skin adsorption of toluene, styrene
     and xylene by man.  Br. J. Med.  25(3):243.

El Masri, A.M., J.N. Smith and R.T. Williams.  1956.  Studies in detoxication.
     69.  The metabolism of alkylbenzenes:  n-propylbenzene and n-butylbenzene
     with further observations on ethylbenzene.  Biochem. J.  64:50-56.

ESE.  1982.  Environmental Science and Engineering, Inc.  ESE review of
     organic contaminants in ODW data base for summary of all available
     treatment techniques:  Toluene.  Office of Drinking Water, U.S.
     Environmental Protection Agency.  EPA No. 68-01-6494.

Frei, J.V., and W.F. Kingsley.  1968.  Observations on chemically induced
     regressing tumors of mouse epidermis.  J. Natl. Cancer Inst.  41:1307-
     1313.

Frei, J.V., and P. Stephens.  1968.  The correlation of promotion of tumor
     growth and of induction of hyperplasia in epidermal two-stage carcino-
     genesis.  Br. J. Cancer.   22:83-92.

Gamberale, F., and M. Hultengren.  1972.  Toluene exposure.  II.  Psychophysio-
     logical functions.  Work Environ.  Health.  9(3):131-139.  (CA 79:950-
     1973).

Grabski, D.A.  1961.  Toluene sniffing producing cerebellar degeneration.
     Am. J. Psychiatry.  118:461-462.

Greenburg, L., M.R. Mayers, H. Heimann and S. Moskowitz.  1942.  The effects
     of exposure to toluene in industry.  J. Am. Med. Assoc.  118:573-578.

Hanninen, H., L. Eskelinen, K. Husman and M. Nurmineen.  1976.  Behavioral
   .  effects of long-term exposure to a mixture of organic solvents.  Scand.
     J. Work Environ. Health.   2(4):240-255.

Hudak, A., and G. Ungvary.  1978.  Embryotoxic effects of benzene and its
     methyl derivatives:  toluene, xylene.  Toxicology.  11:55-63.

IARC. 1982.   International Agency for Research on Cancer. IARC monographs
     on the evaluation of the carcinogenic risk of chemicals to humans.
     Supplement 4.  Lyon, France.

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                                     -15-
Kimura, E.T., D.M. Ebert and P.W. Dodge.  1971.  Acute toxicity and limits
     of solvent residue for sixteen organic solvents.  Toxicol. Appl. Pharmacol.
     19(4):699-704.

Knox, J.W., and J.R. Nelson.  1966.  Permanent encephalopathy from toluene
     inhalation.  N. Engl. J. Med.  275:1494-1496.

Kroeger, R.M., R.J. Moore, T.H. Lehman,  J.D. Giesy and E.D. Skeeters.  1980.
     Recurrent urinary calculi associated with toluene sniffing.  J. Urol.
     123(1):89-91.

Lutin,  P.A., J.J. Cibulka and G.W. Malaney.  1965.  Oxidation of selected
     carcinogenic compounds by activated sludge.  Purdue Univ., Eng. Bull.
     Ext. Ser.  118:131-145.

Mabey,  W.R., J.H. Smith, R.T. Podoll et al.  1981.  Aquatic fate process
     data for organic priority pollutants:  Final draft report.  U.S. EPA,
     Washington, D.C.  EPA 440/4-81-014.

Marion, C.V., and G.W. Malaney.  1963.  Ability of activated sludge microor-
     ganisms to oxidize aromatic organic compounds.  Proc. Indus. Waste Conf.
     18:297-308.  (CA 62:1437a, 1965)

Matsushita, T., Y. Arimatsu, A. Ueda, K. Satoh and S. Nomura.  1975.  Hema-
     tological and neuro-muscular response of workers exposed to low concen-
     tration of toluene vapor.  Ind. Health.  13:115-121.

Moss, A.H., P.A. Gabow, W.D. Kaehny, S.I. Goodman and L.L. Haut.  1980.
     Fanconi's syndrome and distal renal tubular acidosis after glue sniffing.
     Ann. Intern. Med.  92:69-70.

Munchinger, R.  1964.  Der nachweis central nervoser storungen bei losung-
     smitt el-exponierten arbeitern.  Excerpta Medica Series, Madrid; 16-21.
     2(62):687-689.  (Ger.)

Nawrot, P.S., and R.E. Staples.  1979.  Embryo-fetal toxicity and teratogen-
     icity of benzene and toluene in the mouse.  Teratology.  19:41 A. (Abst.)

NCI.  1983.  National Cancer Institute.   National Toxicology Program/Carcino-
     genesis Testing Program.  Chemicals on Standard Protocol:  Management
     Status, June 15.  Tech. Info. Sec.  CTP/NTP.  Bethesda, Md.

Nomiyama, K., and H. Nomiyama.  1974.  Respiratory retention, uptake and
     excretion of organic solvents in man.  Benzene, toluene, n-hexane,  tri-
     chloroethylene, acetone, ethyl acetate and ethyl alcohol.  Int. Arch.
     Arbeitsmed.  32(1-2):75-83.

Ogata,  M., K. Tomokuni and Y. Takatsuka.  1970.  Urinary excretion of hippuric
     acid and m- or p-methylhippuric acid in the urine of persons exposed to
     vapours of toluene and m- or p-xylene as a test of exposure.  Br. J. Ind.
     Med.  27(1):43-50.

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                                     -16-
Patterson, J.W., and P.S. Kodukala.  1981.  Biodegradation of hazardous
     organic pollutants.  Chem. Eng. Prog.  77(4):48-55.

Powers, M.B.  1979.  Chemical selection meetings on toluene.  Memorandum for
     the record from the NTP Chemical Selection Group, Toxicology Branch,
     CGT, DCCP, National Institute, Washington, D.C., May 25.

Price,  K.S., G.T. Waggy and R.A. Conway.  1974.  Brine shrimp bioassay and
     seawater BOD of petrochemicals.  J. Water Pollut. Control Fed.  46(1):63-77.

Pyykko, K., H. Tahti and H. Vapaatalo.  1977.  Toluene concentrations in
     various tissues of rats after inhalation and oral administration.  Arch.
     Toxicol.  38:169-176.

Riihimaki, V.  1979.  Conjugation and urinary excretion of toluene and m-xylene
     matabolites in a man-.  Scand . J. Work Environ. Health.  4( 1 ) : 1 35-1 42.

Sasa, M., S. Igarashi, T. Miyazaki, K. Miyazaki,  S. Nakano and I. Matsuoka.
     1978.  Equilibrium disorders with diffuse brain atrophy in long-term
     toluene sniffing.  Arch. Oto-Rhino-Laryngol.  221 ( 3) : 1 63-169.

Seppalainen, A.M., K. Husman and C. Martenson.  1978.  Neurophysiological
     effects of long-term exposure to a mixture of organic solvents.  Scand.
     J. Work Environ. Health.  4(4) :304-31 4.

Smith,  J.N., R.H. Smithies and R.T. Williams.  1954.  Studies in detoxication.
     55.  The metabolism of alkylbenzenes :  (a) Glucuronic acid excretion
     following the administration of alkylbenzenes:  (b) Elimination of toluene
     in the expired air of rabbits.  Biochem. J.  56:317-320.

Smyth,  H.F., Jr., C.P. Carpenter, C.S. Weil, U.C. Pozzani, J.A. Striegel, and
     J.S. Nycum.  1969.  Range-finding toxicity data.  List. VII.  Am. Ind.
     Hyg. Assoc. J.  30(5) :470-476.

Sutton, C., and J.A. Calder.  1975.  Solubility of alkylbenzenes in distilled
     water and seawater at 25°C.  J. Chem. Eng. Data.  2( 3) : 320-322.
     (CA 83:104181q, 1975)

Tabak,  H.H., S.A. Quave, C.I. Mashni and E.F. Earth.  1981.   Biodegradability
     studies with organic priority pollutants compounds.  J. Water Pollut.
     Control Fed.  51:1503-1518.

Tute, M.S.  1971.  Principles and practice of Hansch analysis:   A guide to
     structure-activity correlation for the medicinal chemist.  Adv. Drug. Res.
     5:1-77.

U.S. EPA.  1980.  United States Environmental Protection Agency.  Water
     quality criteria documents; availability.  Federal Register 45(231):
     79318-79379.

U.S. EPA.  1983.  U.S. Environmental Protection Agency.  Ground Water Supply
     Survey.  Computer data file provided by Office of Drinking Water, Technical
     Support Division, U.S. EPA, Cincinnati, OH.

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                                      -17-
 U.S.  EPA.   1985a.   U.S.  Environmental  Protection Agency.   Drinking water
      criteria  document for  toluene  (Final Draft).  March,  1985.

•U.S.  EPA.   1985b.   United States  Environmental  Protection Agency.   Method
      503.1.  Volatile aromatic and  unsaturated  organic  compounds in water by
      purge  and trap gas  chromatography.  Environmental  Monitoring  and  Support
      Laboratory, Cincinnati, Ohio 45268.

 U.S.  EPA.   1985c.   U.S.  Environmental  Protection Agency.   Method 524.1.  Volatile
      organic compounds in water by  purge and  trap gas chromatography/mass
      spectrometry.   Environmental Monitoring  and Support  Laboratory, Cincinnati,
      Ohio 45268.

 U.S.  EPA.   1985d.   U.S.  Environmental  Protection Agency.   National primary
      drinking  water regulations;  Synthetic organic chemicals,  inorganic
      chemicals and  microorganisms;  Proposed Rule.  Federal Register.
      50(219):46936-47022.   November 13.

 U.S.  EPA.   1986.  U.S. Environmental Protection Agency.   Guidelines for
      carcinogen risk assessment.  Federal Register 51(185);33992-34003.
      September 24.

 von Oettingen,  W.F., P.A. Neal, D.D. Donahue, et al.  1942a.   The  toxicity
      and potential  dangers  of  toluene, with special reference  to its maximal
      permissible concentration.   U.S.  Public  Health Service Pub.,  Bull. No.
      279.   p.  50.

 von Oettingen,  W.F., P.A. Neal, and D.D. Donahue.  1942b.   The.toxicity and
      potential dangers of toluene — Preliminary report.   J. Am. Med.  Assoc.
      118:579-584.

 Weast,  R.C., ed.  1977.  CRC handbook  of chemistry and  physics, 58th ed.
      Chemical  Rubber Co., Cleveland, OH.

 Wilson, R.H.   1943. Toluene poisoning.  JAMA.   123:1106-1108.

 Wolf,  M.A.,  V.K. Rowe, D.D. McCollister, R.C. Hollingsworth and F. Oyen.
      1956.   Toxicological studies of certain  alkylated  benzenes and benzene.
      Arch.  Ind. Health.  14:387-398.

 Zoeteman, B.C.J., A.J.A. Kraayeveld and C.J.  Piet.  1971.   Oil pollution and
      drinking  water odors.  Water 4(16):367-371.

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