un«ed States                                  • DRAFT
               Environmental Protection                         ECA6-CIN-U029
                                                    December, 1987
v°/EPA       Research  and
               Development
               DRINKING WATER HEALTH ADVISORY-FOR
               1.2.4-TRIMETHYLBENZENE
               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: 00 NOT CITE OR QUOTE


                                 NOTICE

           This document I* a preliminary draft.  It has not been formally released
        by the U.S. Environmental Protection Agency and should not at this stage be
        construed to represent Agency policy.  It Is being circulated for comments
        on Its technical accuracy and policy Implications.

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                                         DISCLAIMER

                   reP°r*  ^s  an  external draft  for  review purposes  only  and does not
          constitute  Agency  policy.   Mention of  trade  'names  or  commercial products
               not  constitute endorsement or  recommendation for use.
                                     Repository Material
                                    Permanent Collection
Cs.
                                       '  "     US ERA
                                  -Headquarters and Chamic?"? Libraries
                                      EPA West Bldg Room 3340
                                           Ma'lcode 3-?04T
                                      1301 Constitution Ave
                                       - Washington DC 20004
                                         •   202-5SS-C55S
                                              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 noncardnogens,  and carcinogenic potency  values
for known carcinogens.

    In  the  development of  this Health  Advisory,  the  scientific  literature
has  been  Inventoried  and  key  studies  ha-ve  been  evaluated.    Both  the
published literature  and  Information  obtained  from Agency program  offices
have been evaluated.   The literature  search  Is current  through  1985.   Hore
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.
                                       111

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1,2,4-Trlmethylbenzene               -1-                     February  12,  1988
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-
lation.

       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
noncarclnogenlc  endpolnts  of  toxldty.   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  1s.  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,
Loglt  or Problt, 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.

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1.2,4-TMmethylbenzene
 -2-
February 12,  1988
II.    GENERAL INFORMATION AND. PROPERTIES
       Synonyms
                Asymmetrical      tMmethylbenzene;      uns-trlmethylbenzene;
                psl-cumene; pseudocumene; pseudocumol; as-trlmethylbenzene
       Uses
                1,2,4-Trlmethylbenzene   Is   used   In   the   manufacture  of
                trlmellltlc  anhydride,   dyes,   Pharmaceuticals,  perfumes,
                resins  and  pseudocumldlne   (Ulndholz.   1983).    It  1s  a
                component of gasoline (Verschueren,  1983).
       Properties
       Chemical Structure
       CAS f
       Chemical formula
       Molecular weight
       Physical state (at 25°C)
       Melting point
       Boiling point
       Vapor pressure (25*C)

       Specific gravity (20/4°C)
       Hater solubility (25°C)
       Octanol/water  partition
         coefficient  (log Kow)
       Conversion factor
       (25°C.  760 mm  Hg)
    CH,
    I
                                              CH3
     CH,

95-63-60
C9H12
120.19
liquid
-43.78-C
170°C
2.03 mm Hg

0.8761
57 mg/L

3.78

1 mg/m8 = 4.91  ppm
Ulndholz. 1983
Ulndholz. 1983
Ulndholz. 1983
Mackay and Sh1u.
1981
Ulndholz. 1983
Mackay and Sh1u,
1981
Hansch and Leo.
1985

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1,2,4-Trlmethylbenzene                -3-                    February 12, 1988



       Taste threshold  (water)

       Odor threshold (water)

       Odor threshold (air)          0.2 mg/m3               Verschueren, 1983

       Occurrence

                In methodology reports (I.e.,  no mention was made  of  efforts
                to  ensure  representative  samples),   1,2,4-tMmethylbenzene
                was  reported   1n   single  samples  of  drinking  water   In
                Cincinnati,  OH  at  a  concentration  of 0.127  yg/L  (Coleman
                et al.,  1984)  and  In  drinking  water  from Kltakyushu,  Japan
                at a  concentration  of 3.3 pg/L  (Shlnohara  et  al..  1981).
                Concentrations  ranging   from   0.002-0.540  jig/L   have been
                detected  In  seawater from  the  Narragansett  Bay (Wakeham  et
                al.,  1983).

                The mean  atmospheric  concentration of  1,2,4-trlmethylbenzene
                In  various  urban/suburban  areas  In sthe  United  States   Is
                reportedly    1.2    ppb   (5.9    yg/m8),    and    the   mean
                concentration   Is   reportedly   0.580   ppb  (2.8   yg/m8)   In
                rural/remote    areas   (Brodzlnsky    and    Singh.    1982).
                1,2,4-Trlmethylbenzene  Is  emitted   In  the  exhaust from
                highway vehicles (Hampton et al.. 1982).

       Environmental Fate

            •   Based on  experimental  equilibrium data (Hlne and  Hookerjee,
                1975),   the  Henry's  Law  constant  for  1,2,4-trlmethylbenzene
                at  25°C  Is  0.00563  atm-ma/mole.   Given   this   value  and
                using the method  of Lyman et  al.  (1982). the  volatilization
                half-life of  1,2,4-trlmethylbenzene  from a  river  1   m deep
                flowing 1 m/sec with  a wind velocity of 3 m/sec  Is estimated
                to be  3.4  hours.   Thus,  1,2,4-trlmethylbenzene Is  expected
                to be highly volatile from water.

                The  rate  of  blodegradatlon   of  1,2,4-trlmethylbenzene   In
                natural water  cannot be  predicted from the available data.
                In  combination  with the other  water  soluble compounds  of
                petroleum oil.  1,2,4-trlmethylbenzene  was blodegraded using
                a seawater  Inoculum  (van  der Linden, 1978) and a  groundwater
                Inoculum  (Kappeler   and  Wuhrmann,    1978).   Perry   (1979)
                reported  the   co-oxidation  of   1,2,4-trlmethylbenzene   by
                Nocardla coralllna  V-49.  Various  strains of  Pseudomonas  are
                capable  of  blodegradlng  1,2,4-trlmethylbenzene  (Kunz  and
                Chapman, 1981; OmoM and Yamada, 1969).

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1,2,4-Trlmethylbenzene               -4-                    February  12,  1988



III.   PHARNACOKINETICS

       Absorption

                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.   Wkulskl  and  VMglusz  (1975)  as
                well as Cerf  et al.  (1980)  demonstrated the uptake of  1,2.4-
                trlmethylbenzene  after   oral   administration   In  rats   and
                rabbits.   Sandmeyer  (1981)   listed  the systemic toxlclty  of
                1,2,4-trlmethylbenzene  via   Inhalation In  mice,   Indicating
                that absorption of this chemical does occur.

       Distribution

                Gerarde    (1959)   reported   that    due    to   their    high
                llpophlllclty, ~85X  of alkylbenzenes  1n  blood are  bound  to
                red  blood  cells.   Alkylbenzenes  generally  accumulate  In
                tissues with high Upld content.
       Metabolism
                In  general,  alkylbenzenes   are  metabolized  by  side  chain
                oxidation  to  form  alcohols  or  carboxyllc  acids.   These
                compounds  are   then   conjugated  with   glucuronlc  acid  or
                glyclne  for  urinary  excretion.  These  reactions  probably
                occur primarily 1n liver mlcrosomes (Gerarde, 1959).

                Mlkulskl  and Wlglusz  (1975)  reported  that  after  a  single
                oral  dose of  1200 mg/kg of 1,2,4-trlmethylbenzene  to  male
                Wlstar  rats,  a total  of 62.5X  of  the  dose was  excreted  In
                the  urine  as glyclne,  sulfuMc  acid   and  glucuronlc  acid
                conjugates.   The  elimination half-lives  for  these conjugates
                were  9.5  hours   for  glyclne  conjugates,  22.9  hours  for
                glucurmlde and 37.6 hours for organic sulfates.

                Cerf   et  al.   (1980)  administered  0.5   mL/kg/day   (438
                mg/kg/day)  1,2,4-trlmethylbenzene  by gavage to  male albino
                rabbits  for  5 days.   The two  principal  metabolites found  -1n
                urine were  2,4-d1methylbenzo1c  acid  and  3,4-d1methylh1ppuMc
                acid.

                Bakke  and Schellne  (1970)   reported  that  the  only phenolic
                metabolite detected  In  the  urine of  two  rats within 48 hours
                after  an oral dose of  1,2,4-trlmethylbenzene  was 2,4,5-tr1-
                methylphenol.   This  metabolite  amounted  to only  a fraction
                (0.05X)  of the original  dose of  1,2,4-trlmethylbenzene.

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1,2,4-Trlmethylbenzene                -5-                    February 12, 1988
       Excretion
                Gerarde (1959)  reported  that  alkylbenzenes  In  general  are
                eliminated  unchanged   through   the   lungs  or   as   blotrans-
                format Ion  products  In the  urine.   The  urinary metabolites
                (glyclne and  glucuronlde  conjugates) are  water soluble.  A
                small   amount  of  the  parent  compound  may  be  excreted  In
                urine, but this Is limited--by-Us Tow water  solubility.  The
                amount of  the parent  compound  eliminated  through  the  lungs
                In exhaled air depends on the  concentration  In  the  blood and
                the vapor  pressure.

                Mlkulskl   and  Wlglusz   (1975)   reported   the   Following
                elimination     half-times      for     1,2,4-trlmethylbenzene
                metabolites  1n  male  Wlstar   rats:  9.5  hours  for  glyclne
                conjugates; 22.9  hours  for  glucuronlde  and  37.6   hours for
                organic sulfates.
IV.    HEALTH EFFECTS

       Humans

       Short-Term Exposure
                No  data  on   short-term   exposures   to  humans   by   1,2,4-
                trlmethylbenzene were located In the available literature.
       Lonqer-Term Exposure
                The  only  published  report of  human  exposures  (Baettlg  et
                al.( 1958) describes  an  occupational  health Investigation of
                27 painters working  1n  a plant using  the  solvent  Fleet-X DV
                99.   Chemical  analysis  of  this  solvent  showed  that  It
                consisted  of   97.5X  aromatic  hydrocarbons  and   2.5X  of
                parafflnlc   and    napthenlc    hydrocarbons.     Spectography
                Identified >50% of  the  solvent  to  be 1,2,4-trlmethylbenzene
                and  >30%  to  be 1,3,5-trlmethylbenzene.   Rough  quantltatlon
                of the exposure levels  to  the  solvent, using Indicator tubes
                for  benzene  and  Us homologs,  demonstrated air  concentra-
                tions between  10 and  60 ppm.    If  these vapors were  exclu-
                sively tMmethylbenzenes.  this  would  correspond  to a concen-
                tration   range  of   2.0-12.2   mg/ma.    Compared   with   10
                unexposed  unskilled  workers as controls,  clinical  findings
                In  the  exposed Included:   subjective  complaints  of central
                nervous system characteristics  (vertigo,  headaches, drowsi-
                ness),   chronic   asthma-like   bronchitis   (classification
                criteria  not  specified),  hyperchromlc anemia  (<4.5 million
                erythrocytes/mm2) and disturbances In blood clotting.

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1.2,4-Trlmethylbenzene               -6-                    Febroary  12,  1988



       Animals

       Short-Term Exposure

                After  absorption  Into  the  blood,  alkylbenzenes  In  general
                have  two  principal  toxic effects  In  tissues;  Irritation and
                Injury  of  endothellal  tissue  and  central  nervous  system
                depression (Gerarde, 1959).

                Gerarde   (1959)  reported   that   2.5   ml   of   a   mixture  of
                tMmethylbenzene Isomers  In olive oil (1:1 v/v)  administered
                by  gavage to rats weighing 250  g caused  death 1n 7/10.   No
                other  details  were  reported.   Given  an  average density  of
                0.87  for  the trlmethylbenzene mixture  (Hlndholz.  1983), the
                average trlmethylbenzene dose was -4.4 g/kg.

                Cameron   et   al.   (1938)   conducted   short-term   Inhalation
                exposures  to  rats  and  mice  with a  sample  from  coal  tar
                fractional  distillation containing  -70%  crude aromatlcs  of
                the  1,2,4-tr1methylbenzene-l,3,5-tr1methylbenzene type.   No
                pathological changes  were noted   In the major  organs  of  rats
                (n=8)  and  mice  (n=10)  exposed  to  1800-2000 ppm  of  this
                sample  (8852-9836  mg/m3   assuming  exclusive  trlmethylben-
                zene  content;  experiments  were performed at 20°C and  760 mm
                Hg  Is assumed) for  48 and  12 continuous hours  to  rats and
                mice,  respectively.   No  adverse effects  were  noted  1n six
                rats  exposed  to  the  same  sample  at 1800-2000  ppm  for  14
                exposures of 8 hours each.

       Dermal/Ocular  Effects

                Gerarde (1959)  reported  that  direct skin  contact  with liquid
                alkylbenzenes causes vasodllatlon, erythema and Irritation.

       Longer-Term Exposure

                Bernshteln  (1972)  reported  that  Inhalation  of  trlmethyl-
                benzene   (mixture  of  1,2,3-, 1,2,5- and  1,3,5-lsomers)  at
                1000  mg/ma,  4  hours/day for  6  months  Inhibited phagocytlc
                activity  of leukocytes  1n 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  0V 99 (see chemical analysis
                description  under  human longer-term  exposure  section) for 4

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1,2,4-Trlmethylbenzene               -7-                    February 12, 1988
                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  tMmethylbenzenes,  these
                exposures  correspond  to  8360   and  2459 mg/m3,  respective-
                ly.    Differences  between  exposed  rats and  controls  were
                determined  for  the  following:   mortality,  behavior,  weight,
                drinking water  and food  Intakes,  urine dilution and concen-
                tration  tests,  urinary  phenol   excretion and  red  and  white
                differential  blood cell counts.   Four  of the 8 rats exposed
                to 8360  mg/m3  died  within  the  first  2 weeks  whereas  none
                died   In  the  2459 mg/m3  exposure  group.   Body  weight  was
                decreased  In  both  exposure   groups  but   the  effect  was
                confounded  by a  decrease  In food Intake.   Severe excitation
                with   subsequent  narcosis  and  ataxla toward the  end of the
                dally exposure  period  was  exhibited  In  the  high  exposure
                group but  only  Indicated  In  the 2459 mg/ma  group.  These
                phenomena   receded   within   a   few   hours   postexposure.
                Increases In water Intake, urinary diuresis and excretion  of
                free, total  and  bound  phenols were  noted In  the exposed
                rats.  Blood  analysis  also revealed  a relative  lymphopenla
                and    neutrophlUa   In    the    exposed  rats.    Hlstologlc
                examination   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 swelling and  fatty Infiltration  In
                the   kidney,  peripheral  fatty Infiltration   In  the liver,  an
                Increase In  secondary  nodules  In   the  spleen,  and marked
                congestion  of  the pulmonary capillaries with  alveolar wall
                thickening.

       Reproductive Toxldtv

            •   Data   regarding  the  reproductive  toxlclty  of  1,2,4-trl-
                methylbenzene .could   not  be   located  In  the  available
                literature.

       Developmental  Toxldtv

                Data   regarding  the   developmental   toxlclty   of   1,2,4-tM-
                roethylbenzene  could   not  be   located  In . the  available
                literature.

       HutaqenUUv

                Data   regarding   the  mutagenlclty  of  l,2,4-tr1m°thylbenzene
                could not be located  In  the  available literature.

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1,2.4-Trlmethylbenzene               -8-                    February  12.  1988
       Carclnoqenlcity

                Data   regarding   the  carclnogenlclty  of   1,2,4-trlmethyl-
                benzene  could  not  be  located  In  the available  literature.
                The  chemical  has  not  been  selected  for  carclnogenlclty
                testing  (NTP. 1987)  -


V.     QUANTIFICATION OF TOXICOLOGICAL EFFECTS

       Health Advisories are based  upon  the Identification  of  adverse health
effects  associated  with  the most  sensitive and  meaningful  noncarclnogenlc
endpolnt of  toxlclty.   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:


               (NQAEL OR LOAEL)  (BW)
               [UF(s)l  (     L/dav)
where:
         NOAEL     = No-Observed-Adverse-Effect Level
                     (the exposure dose  In rag/kg bw/day)
or
         LOAEL     = Lowest-Observed-Adverse-Effect Level
                     (the exposure dose  In mg/kg bw/day)

         BM        = Assumed body weight  of protected Individual
                     (10 kg for child or  70 kg for adult)

         UF(s)     = Uncertainty factors,  based  upon  quality  and nature
                     of  data  (10,   100,  1000 or  10,000  1n  accordance
                     with NAS/ODW or Agency guidelines)

         	 L/day - Assumed water consumption
                     (1 L/day  for child  or 2  L/day for adult)

       1-Day Health Advisory

            Data  were  not  sufficient   for   derivation  of  a  1-day HA  for
1,2,4-trlmethylbenzene.

       10-Day Health Advisory

            Data  were  not  sufficient   for  derivation  of  a  10-day HA  for
1,2,4-trlmethylbenzene.

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1.2,4-Trtmethylbenzene                -9-                    February 12. 1988
       Longer-Term Health Advisory

            Data were not  sufficient  for  derivation of a longer-term health
advisory.    Although  significant  results   were   Indicated   In  both   the
Bernshteln (1972) and the  Baettlg et  al.  (1958) studies, the exposures were
to  mixtures  of   trlmethylbenzenes.  which  makes  quantUatlon   of  single
components equivocal.  Additional deficits Include the lack of more than  one
exposure level and  detail  (e.g.,  number  of  ar7lmals not  specified, degree of
Inhibition not quantUated)  In  the Bernshteln  (1972)  study.  The  Baettlg et
al.  (1958)  animal  Investigations  lacked  proper  reporting of results (I.e..
statistical  analyses  either  not done or  not  specified)  and techniques,  was
not  comprehensive  In  scope  (I.e.,  hlstologlc  examination 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  noncarclnogenlc adverse  health effects  over  a  lifetime exposure.   The
lifetime  HA  Is  derived  1n  a  three  step  process.   Step  1  determines  the
Reference  Dose   (RfD),  formerly  called  the Acceptable  Dally  Intake  (ADI).
The  RfD  Is  an  estimate  (with  uncertainty  spanning  perhaps   an order  of
magnitude) of a  dally exposure to the human population  (Including sensitive
subgroups)  that  Is  likely  to  be without  appreciable  risk  of  deleterious
health effects  during a lifetime, and 1s derived  from the  HOAEL (or  LOAEL),
Identified  from  a chronic (or  subchronlc)  study,  divided by an uncertainty
factor(s)  times  an additional  uncertainty factor.  From  the RfD.  a  Drinking
Water  Equivalent  Level  (DUEL)  can  be determined (Step  2).   A  DWEL  Is  a
medium-specific  (I.e..   drinking water)  lifetime  exposure  level,  assuming
100X  exposure from that  medium,  at which  adverse,  noncarclnogenlc  health
effects  would  not be  expected  to  occur.   The  DUEL   Is  derived from  the
multiplication of  the RfD  by the assumed  body  weight  of  an adult and divided
by  the assumed  dally water  consumption  of an  adult.   The  lifetime  HA In
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,  1f  data  are  not  available,  a
value  of  20X 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  noncarclnogenlc  endpolnts of
toxlclty.   In order  to assist  the  risk manager  In this  process,  drinking
water  concentrations associated with estimated  excess  lifetime cancer  risks

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1,2,4-TMmethylbenzene                -10-                   Febroary 12,  1988
over  the  range  of  1  In 10,000 to 1 in 1,000,000 for the 70 kg adult drinking
2  L of water/day  are provided  In the  Evaluation  of  Carcinogenic  Potential
Section.

            Data  were not  sufficient  for  derivation  of  a  lifetime  health
advisory  for the same  reasons specified  for the longer-term health advisory.

       Evaluation of Carcinogenic  Potential

            Pertinent  data  regarding  the carclnogenlclty of 1,2,4-trlmethyl-
benzene could not  be  located  In the available literature.   This chemical has
not  been  scheduled for  carclnogenlclty testing  (NTP,  1987).  IARC has not
evaluated the carcinogenic  potential of  1.2,4-trlmethylbenzene.

            Applying  the  criteria  described 1n the U.S. EPA's Guidelines for
Carcinogen  Risk Assessment (U.S.  EPA,  1986a), 1,2,4-trlmethylbenzene  may be
classified  1n  Group  D:   Not  classified.   This  category signifies  that the
evidence  Is Insufficient  to assess  the agent's carcinogenic potential.


VI.    OTHER CRITERIA. GUIDANCE AND STANDARDS

       ACGIH  (1980,   1985)  recommended  a  TLV  of  25  ppm  (-5  mg/m3)  and  a
STEL  of  35 ppm (~7  mg/ma) for mixed trlmethylbenzenes.   These  numbers are
based largely on human experience with trlmethylbenzenes.


VII.   ANALYTICAL METHODS

       Analysis  of   1,2,4-tr1methylbenzene   1s   by   a  purge-and-trap   gas
chromatographlc  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  1s
heated to drive off  compounds  onto a  gas chromatographlc column.  The gas
chromatograph  Is  temperature  programmed  to  separate  the method  analytes.
which are then detected  by the  photolnonlzatlon  detector.  This  method 1s
applicable  to the  measurement  of 1,2,4-tr1methylbenzene over  a concentration
range  of  0.06-1500  yg/L.   Confirmatory  analysis  Is  by   mass  spectrometry
(U.S.  EPA.  1985b).    The  detection   limit  for  confirmation   by  mass
spectrometry has not been determined.


VIII.  TREATMENT TECHNOLOGIES

       Very  little   Information   Is   available  on  treatment  technologies
capable of  removing 1,2,4-trlmethylbenzene from water.

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1,2,4-TMmethylbenzene               -11-                   February  12,  1988
       Muller et  al.  (",381)  presented mass  transfer  coefficients for  non-
polar  volatile  organic  compounds.  Including 1,2,4-tr1methylbenzene.   They
concluded that  In  bubble aeration systems  mass  transfer  rates  for  volatile
compounds depend on mass transfer  rate coefficients  as well  as  the degree of
saturation of the exit gas.

       U.S.    EPA    (1986b)    estimated    the   feasibility    of    removing
1.2.4-tr1methy1benzene   from  water   by   alrr   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, 90X removal  efficiency
of 1,2,4-trlmethylbenzene was reported by  a  column  with a  diameter of 5.8 ft
and  packed  with 15  ft of  1  Inch plastic  saddles.   The air-to-water  ratio
required  to  achieve  this  degree  of  removal  effectiveness   Is 25.   Actual
system  performance  data, however, are  necessary to  realistically determine
the   feasibility    of   using    air   stripping    for   the    removal    of
1,2,4-trlmethylbenzene from contaminated  drinking water.

       In  summary,   the  amenability   of  1,2,4-trlmethylbenzene   to   air
stripping  has   been   clearly  established.   Selection of  air  stripping  to
attempt 1,2,4-trlmethylbenzene removal from contaminated  drinking  water  must
be  based  on  a  case-by-case  technical evaluation and an  assessment of  the
economics Involved.


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ACGIH  (American Conference  of   Governmental  Industrial  Hyglenlsts).   1985.
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Baettlg,  K.,   E.   Grandjean,   L.   Rossi   and   J.  Rlckenbacher.    1958.
Toxlkologlsche    Untersuchungen    Ueber    Trlmethylbenzol.     (Toxlcologlcal
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Bernshteln.  L.N.   1972.   Phagocytosis  reaction In  experimental  animals  on
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         -12-
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1,2,4-Trlmethylbenzene               -14-                  February 12,  1988
VMndholz. H..  Ed.  19B3.   The  Merck Index,  10th ed.  Herck  and  Co.,  Inc.,
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