March  31,  1987

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

        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

        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.

                   March 31,  1987
         This Health Advisory  (HA)  is  based on information presented in the
    Office of Drinking Water's Health  Effects Criteria Document (CD) for Styrene
    (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  # 86-118056/AS.  The toll-free number is (800)
    336-4700; in the Washington,  D.C.  area: (703) 487-4650.
    CAS No.   100-42-5
    Structural Formula
                          CH .  CH.
    Sy nony ms
            Vinyl benzene,  cinnaraene,  phenylethylene,  ethenylbenzene
            Styrene plastics  .

    Properties  (Hansch and Leo,  1979; Lewis et al.,  1983)
            Chemical Formula
            Molecular Weight
            Physical State
            Melting Point
            Density (20°C)
            Vapor Pressure (20*C)
            Water Solubility
            Log Octanol/Water Partition
            Conversion Factors
Clear, colorless liquid with a
  characteristically sweet and
  pleasant odor
30.86 g/cm3
4.53 torr
6.18 torr
320 mg/L
            0.235 ppm
            4.26 mg/m3
                                                  1 ppm
            Styrene is produced primarily from the dehydrogenation of ethylbenzene,
            In  1982, the U.S production of styrene totaled 5.9 billion pounds.

     Styrene                                                          March 31,  1987

             National drinking water surveys indicate that styrene is an infrequent
             contaminant.   To date,  the testing of 941  ground water supplies and
             102 surface water supplies has failed to result in the detection of
             a single positive occurrence (Boland,  1981).

             Contamination of drinking water by styrene, however,  has been reported
             occasionally  by State programs.


          0  Available data indicate that the absorption of styrene from the
             gastrointestinal tract of rats is rapid and virtually complete
             (Plotnick and Weigel,  1979).

          0  Styrene uptake and absorption has been the subject of a number of
             human inhalation studies (Fiserova-Sergerova and Teisinger, 1965;
             Teramoto and Horiguchi, 1979). The findings of these studies indicate
             that pulmonary retention of styrene is approximately 2/3 of the
             administered concentration with considerable variation in measured
             uptake between individuals and studies (mean uptakes ranged from
             59 to 89%).


          0  The distribution of styrene following oral administration was studied
             in rats given single doses of 20 mg/kg 14C-styrene in corn oil by
             gavage (Plotnick and Weigel,  1979).  Peak tissue levels were reached
             within 2 to  4 hours.  The organs with the highest concentrations were
             kidney (46 ug/g in males; 25  ug/g in females), liver (13 ug/g in
             males; 7 ug/g in females) and pancreas (10 ug/g in males; 6 ug/g in
             females) with lower concentration levels in lungs, heart, spleen,
             adrenals,  brain,  testes and ovaries.

          0  Results from inhalation studies in rats indicate that distribution of
             styrene is widespread with relatively high concentrations in adipose
             tissue (Withey and Collins, 1979).

          0  In humans, Dowty st al. (1976) found concentrations of transplacent-
             ally transferred styrene to be somewhat higher than those of maternal
             blood, which suggests  a selective one-way transplacental transfer.

          0  Pellizzari et al. (1982) detected styrene in each of 8 milk samples
             collected from lactating women residing in various cities.


          0  The metabolic fate of styrene in mammals has been studied extensively.
             There is limited information  from human studies, but similarities to
             the process  in other mammals  have been identified.

    Styrene                                                          March 31,  1987

            Based on studies in rats administered styrene-7,8-oxide or styrene
            glycol by intraperitoneal injection,  Ohtsuji and Ikeda (1971)  have
            proposed that the metabolism of styrene proceeds  via P-450 microsomal
            oxidations to styrene oxide, styrene  glycol, and then to mandelic
            acid which is metabolized to either phenylglyoxylic acid or to benzoic
            the hippuric acid.
            Results from a. number of studies  in rats  (Withey and Collins,  1977,
            1979;  Ramsey and Young,  1978,  1980; Teramoto and Horiguchi,  1979)
            indicate that styrene is eliminated relatively rapidly from  all
            tissues in test animals.

            Twenty-four hours following oral  administration of 20 mg/kg  14C-
            styrene to rats, concentrations in all tissues and organs  examined were
            less than 1 ug/g (Plotnick and Weigel,  1979).

            The elimination of styrene (from the heart,  brain,  liver,  spleen and
            kidney oŁ rats was described by biphasic  log-linear kinetics after
            intravenous injection of 4.0 mg/kg (Withey  and Collins,  1977).   Half-
            lives  ranged from 3.8 to 7.1 minutes for-the alpha (fast)  phase and
            from 20 to 37 minutes for the  beta (slow) phase.

            Predictions based on a toxicokinetic model  (parameters estimated from
            a human inhalation study) indicated that  maximum concentrations of
            styrene in both blood and fat of  humans were reached after a few
            repeated 8-hour daily exposures to 80 ppm styrene, suggesting no
            tendency for long-term accumulation (Ramsey et al., 1980;  Ramsey and
            Young, 1978, 1980).
            Results of controlled experiments using human volunteers  indicate
            that styrene administered by inhalation at relatively high doses
            results in central nervous system (CNS) effects.

            Drowsiness, listlessness and an altered sense of  balance  were
            reported during a 4-hour exposure of two male subjects to styrene
            at 3,407 mg/m3 (800 ppm) (Carpenter et al.,  1944).

            Stewart et al. (1968) reported that volunteers exposed to styrene by
            inhalation at 217 mg/m3 (50 ppm) and 499 mg/m3 (117 ppm)  for 1  and
            2 hours, respectively, showed no signs of toxicity.  The  moderately
           ~strong initial styrene odor diminished after 5 minutes.  At 921  mg/m3
            (216 ppm) nasal irritation resulted after 20 minutes.  Eye and nose
            irritation, strong odor and altered neurological  function were reported
            for volunteers exposed to styrene at 1,600 mg/m3  (376 ppm) for 1 hour.
            Most volunteers exposed to this level exhibited reduced performance
            in the Crawford Manual Dexterity Collar and Pin Test, the modified
            Romberg Test and the Flannagan Coordination Test.  Six subjects were
            exposed to 422 mg/m3 (99 ppm) styrene vapor for seven hours.  No
            serious untowed effects were noted.

Styrene                                                          March 31, 1987

                                     » C —
        Gamberale and Hultengren (1974) exposed 12 subjects to styrene by
        inhalation at concentrations of 213, 639,  1,065 and 1,491 mg/m3 (50,
        150, 250 and 350 ppm) during four consecutive 30-minute intervals.
        A dose-related increase in single reaction time was evident.  Reaction
        time recorded during the final 30-minute exposure was significantly
        increased (p <0.05).

        Odkvist et al. (1982) studied the effects  of styrene on the vestibulo-
        oculomotor functions in 10 subjects exposed to styrene by inhalation
        at 370 to 591 mg/m-3 (88-140 ppm) for approximately 80 minutes.  The
        rate of movement of the eyes between two alternating light sources
        (saccade) increased significantly (p <0.05) after exposure.  Suppression
        of the vestibule-oculomotor reflex was also affected.

        There is suggestive evidence that the human fetus is more sensitive
        than the adult to the toxic effects of styrene (Holmberg, 1977;
        Hemminki et al.,  1980).

        The frequency of spontaneous abortions among Finnish chemical workers
        was analyzed by Hemminki et al. (1980).  Information on spontaneous
        abortions (15,482 cases),  induced abortions (71,235 cases) and births
        (193,897 cases) for 1973-1976 was obtained from the Hospital Discharge
        Registry of the Finnish National Board of  Health and linked by social
        security number to the membership of the Finnish Union of Chemical
        Workers (approximately 900 female members).  About 85% of the total
        number of spontaneous abortions in Finland were reportedly listed in
        the registry.  The rate of spontaneous abortion was defined as the
        number of spontaneous abortions x 100/number of births.  The rates
        of spontaneous abortion were 8.54% (N = 52) and 15.0% (N = 6) among
        the female union members and a subgroup in the styrene industry,
        respectively.  These rates were significantly higher (p<0.01) than
        the rate among all Finnish women (5.52%, 15,482 spontaneous abortions).
        The ratios of spontaneous  abortion were 16 and 32 in the female union
        workers and female styrene industry workers,  respectively, which
        were significantly higher  (p<0.001) than the rate among all Finnish
        women (8%).

        The information on the work histories of 43 Finnish mothers of children
        born with central nervous  system (CNS) defects from June 1, 1976 to
        March 1, 1977 were obtained through personal interviews (Holmberg,
        1977).  Two of these mothers had been employed in the reinforced
        plastics industry with regular exposure to styrene, polyester resin,
        organic peroxides and acetone during pregnancy.  The defects in their
        two children were anencephaly and congenital hydrocephaly.  The
        overall rates of anencephaly and congenital hydrocephaly were reported
        to be 0.2 and 0.3,  respectively,  per 1000  live births in Finland.
        Based on these estimates,  there appeared to be more than a 300 fold
        increased rate of thooo malformations—in- the reinforced plastics
        industry during the 9-month study period compared with the general
        population (2/12 vs 0.5/1000).

Styrene                                                          March 31, 1987



Short-term Exposure

     0  Wolf et al. (1956) reported an acute oral LDgQ °f greater than 5,000
        mg/kg for rats treated with styrene by gavage.  This indicates that
        the acute toxicity of styrene is relatively low.

     0  The lowest single oral dose of styrene (administered by oral intuba-
        tion) causing 100% mortality in rats within two weeks of treatment
        was 8,000 mg/kg,  while 1,600 mg/kg was the maximum dose resulting in
        no deaths (Spencer et al.,  1942).

     0  The effects of styrene administration at 250,  450 or 900 mg/kg orally
        (method not stated) for 7 consecutive days on hepatic mixed function
        oxidase (MFO) enzyme activities, glutathione content and glutathione-
        S-transferase activity were reported by Das et al. (1981).  Activities
        of aryl hydrocarbon hydroxylase and aniline hydroxylase were signifi-
        cantly enhanced at higher doses of styrene (450 and 900 mg/kg).  A
        significant lowering of glutathione content accompanied with the
        inhibition of glutathione-S-transferase activity was also noted at
        the highest dose  of styrene (900 mg/kg).  Therefore, the MOAEL for
        effects on hepatic enzymes  in this study was 250 mg/kg/day.

     0  Agrawal et al. (1982) studied the effects of styrene on dopamine
        receptor binding  in rats.  Styrene was administered at 200 or 400
        mg/kg/day by gavage to groups of 6 eight-week old ITRC male albino
        rats.  Styrene was administered in a single dose or in up to 90 daily
        doses over 90 days.  Significant increases in the specific binding of
        •^H-spiroperidol to dopamine receptors in the corpus stratum were
        noted at both levels^jif-ter  single or repeated exposure to styrene.
        The LOAEL for this study was identified as 200 mg/kg/day.

Long-term Exposure

     0  Changes in hepatic enzyme activity following oral exposure to styrene
        have been demonstrated by a number of investigators.

     0  Srivastava et al. (1982) administered styrene by gavage (at 200 or
        400 mg/kg/day) to groups of 5 adult male albino ITRC rats, 6 days
        per week for 100 days.  These animals did not exhibit any changes in
        weight gain or other overt signs of toxicity.  There were significant
        dose-dependent increases in hepatic enzymes (benzo[a]pyrene hydroxylase
        and aminopyrine-N-deraethylase) as well as decreases (glutathione-S-
        transferase).  There were significant decreases in some mitochondrial
        enzymes as well.   Histopathological changes were seen only at the
        high dose and these consisted of tiny areas of focal liver necrosis,
        consisting of a few degenerated hepatocytes and inflammatory cells.
        Therefore, the LOAEL for hepatic effects was 200 mg/kg/day.

     0  Groups of ten female rats were administered styrene at 66.7, 133, 400
        or 667 mg/kg/day by intubation, five days a week for six months (Wolf

Styrene                                                          March 31, 1987

        et al., 1956).  At the two higher dose levels, decreased growth
        weights and increased liver and kidney weights were observed without
        hematologic or histopathologic effects. At the two lower dose levels,
        no effects were noted on body weight, organ weight or pathology.
        Therefore, the NOAEL for this study was 133 mg/kg/day and the LOAEL
        was 400 mg/kg/day.

     0  Beagle dogs were given styrene in a peanut oil suspension by gavage
        7 days per week for 560 days (Quast et al., 1978).  Dose levels were
        200, 400 or 600 mg/kg bw/day.  The controls received peanut oil only.
        At the two higher dose levels, minimal histopathologic effects were
        noted in the liver (increased iron deposits within the reticulo-
        endothelial cells) as well as hematologic effects that included
        increased Heinz bodies in erythrocytes and a decreased packed cell
        volume.  At the lowest dose level, these effects were not noted.
        Therefore, 200 mg/kg/day was identified as the NOAEL for this study
        and 400 mg/kg/day can be designated as the LOAEL.

Reproductive Effects

     0  The reproductive/teratogenic effects of styrene oxide  were assessed
        in Wistar rats (Sikov et al. 1981).  The percentage of pregnant rats
        was reduced significantly.

Developmental Effects

     0  Investigators at the Dow Chemical Company administered styrene in
        peanut oil to pregnant Sprague-Dawley rats (29 to 39 dams per group)
        by gavage at dose levels of 0, 180 or 300 mg/kg/day (0,  90,  150 mg/kg
        twice daily) on days 6 through 15 of gestation (Murray et al., 1976;
        1978). Maternal toxicity was indicated by significantly, red.useji—
        (p <0.05) body weight gain and food consumption at the higher dose
        level.  There were no significant effects observed on maternal
        mortality or percent pregnancy.  No teratogenic or fetotoxic effects
        were observed.  Therefore, the NOAEL for maternal toxicity was 180

Mutagenici ty

     0  Results were negative for six mutagenicity tests using  Salmonella
        typhimurium test systems, both with and without S-9 metabolic activat-
        ing system.  Styrene was tested using the bacterial strains  TA1535,
        TA1537, TA98 and TA100.  De Meester et al. (1977, 1981)  and  Vainio
        et al. (1976) obtained positive results with mutant strains  sensitive
        to base pair substitution while all tests were negative in strains
        sensitive to frameshift mutagens.

     0  Styrene oxide, a major metabolite of styrene,  has been demonstrated
        consistently to be mutagenic in S_. typhimurium  TA1535 and TA100,
        in the presence and absence of a mammalian metabolic activating
        system (De Meester et al., 1977; 1981).

   Styrene                                                          March 31,  1987


   Carcinogenici ty

        0  Both positive and negative results have been reported in bioassays
           of the potential carcinogenicity of styrene in experimental animals.
           Most of the long-term bioassay results, however,  are characterized  by
           inconsistent observations of elevated tumor formation and excessive
           mortality among treated animals (Jersey et al.,  1978; Ponomarkov
           and Tomatis, 1978; NTP, 1979; Maltoni et al.,  1982).

        0  Retrospective cohort mortality and case-control studies have btien con-
           ducted on workers exposed to styrene in the styrene-polystyrene manu-
           facturing industry and in the styrene-butadiene synthetic rubber industry
           (McMichael et al., 1976; Smith and Ellis,  1977;  Meinhardt et al., 1978).
           There are inadequate data at present to indicate  that styrene is a
           human carcinogen.   However, an elevated incidence of tumors of the
           hematopoietic and lymphatic tissues have been observed.  The available
           studies are limited because of relatively small cohort sizes or
           multiple chemical exposures of workers (including exposure to benzene).


        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)
                        (UF) x (	 L/day)
           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).
   One-day Health Advisory

        The study of Stewart et al. (1968) was seleted as the basis for calculating
   the One-day HA.  The study invloved a controlled styrene inhalation exposure
   using nine healthy human male volunteers.  No subjective or objective signs
   of toxicity were noted following one and two hour exposures to 51  ppm (217
   mg/m3) or 117 ppm (449 mg/m3) styrene respectively.  To simluate a work
   day, six subjects were exposed to 99 ppm (422 mg/m3) styrene vapor for seven

Styrene                                                          March 31, 1987


hours.  From a subjective standpoint, no serious untoward effects were noted except
mild eye and throat irritation in three subjects.  There were no objective
signs of impairment of balance or coordination; however, three of the six
subjects did report that they were having intermittent difficulty in performing
the modified Romberg Test.  In contrast, exposure to 376 ppm (1602 mg/m3)
styrene vapor for one hour resulted in abnormal neurological findings and
complaints of nausea and inebriation.  The result of urinalysis, hematology
and blood chemistry studies were normal and unchanged from pre-exposure

     The results of another study (Odkvist et al., 1982) using human volunteers
exposed to similar styrene levels, indicate that the mean pulmonary styrene
uptake was 64% of the inspired amount.  Using a NOAEL of 99 ppm (422 mg/m3)
from a 7-hour exposure, the One-day Health Advisory for a 10-kg child can be
derived.  First the total absorbed dose (TAD) is determined.

  TAD* = (422 mg/m3) (20 m3/day) (7 hours/24 hours) (0.64)  =22.5 mg/kg/day
                              70 kg

    whe re:

                TAD = total absorbed dose.

          442 mg/m3 = NOAEL,  based on the absence of adverse effects in
                      humans  exposed to styrene by inhalation.

   7 hours/24 hours = duration of exposure.

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

               0.64 = estimated ratio of absorbed dose (Odkvist et al., 1982).

              70 kg = weight of exposed individual (adult).

Therefore the One-day Health  Advisory for a 10-kg child is  as follows:

              One-day HA = (22.5 mg/kg/day) (10 kg) =22.5  mg/L
                               (10)  (1 L/day)


      22.5 mg/kg/day = TAD.

               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 study in  humans.

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

Styrene                                                          March 31, 1987


Ten-day -Health Advisory

     No information was found in the available literature that was suitable
for deriving a Ten-day HA value for styrene.  It is therefore recommended
that the Longer-term HA for a 10-kg child (2 mg/L, calculated below) be
used at this time as a conservative estimate of the Ten-day HA value.

Longer-term Health Advisory

     The Quast et al. (1978) study in dogs has been chosen to serve as the
basis for calculating the Longer-term HAs for styrene.  In this study, beagle
dogs were administered styrene by gavage at 0, 200, 400 or 600 mg/kg/day,
7 days per week, for 560 days.  At the two higher doses, minimal histopathologic
effects were noted in the liver (increased iron deposits within the reticulo-
endothelial cells) as well as hematologic effects that included increased
Heinz bodies in erythrocytes and a decreased packed cell volume.  At the
lowest dose level, these effects were not noted with the possible exception of the.
equivocal observation of low level occurrence of Heinz bodies in a single
female from this group.

     Based on the NOAEL of 200 mg/kg/day determined in this study, the Longer-
term HAs are calculated as follows:

     For a 10-kg child:

       Longer-term HA = (200 mg/kg/day) (10 kg) = 2 mg/L (2000 ug/L)
                          (100) (10) (1 L/day)

        200 mg/kg/day = NOAEL at which no decreased growth weights or increased
                        liver and kidney weights were observed in dogs.

                10 kg - assumed body weight of a child.

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

                   10 = modifying factor for small group size (4 dogs per

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

     For a 70-kg adult:

       Longer-term HA = (200 mg/kg/day) (70 kg) = 7 mg/L (7000 ug/L)
                          (100) (10) (2 L/day)
where all factors are the same except:

                70 kg = assumed body weight of an adult.

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

Styrene                                                          March 31, 1987


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.  For
Group C carcinogens, an additional safety factor of 10 is added to the DWEL.

     The Lifetime HA for a 70-kg adult has been determined on the basis of
the s'tudy in dogs by Quast et al. (1978) as described above.

     Using the NOAEL of 200 mg/kg/day, as determined in that study, the
Lifetime HA is calculated as follows:

Step 1:  Determination of the Reference Dose (RfD)

                  RfD = (200 mg/kg/day) . 0 2 mg/kg/day


        200 mg/kg/day = NOAEL at which no decreased growth weights or increased
                        liver and kidney weights were observed in dogs.

                1,000 = uncertainty factor, chosen in accordance with NAS/ODW
                        guidelines for use with a NOAEL from an animal study
                        of less-than-lifetime duration.

Step 2:  Determination of the Drinking Water Equivalent Level (DWEL)

                 DWEL = (0.2 mg/kg/day) (70 kg) = o.7 mg/L (700 ug/L)
                             (2 L/day) (10)

Styrene                                                          March 31 , 1987



        0.2 mg/kg/day = RfD.

                70 kg * assumed body weight of an adult.

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

Step 3:  Determination of the Lifetime Health Advisory

             Lifetime HA » (7 mg/L) (20%) - 0.14 mg/L (140 ug/L)

        7 mg/L » DWEL.

           20% = assumed relative source contribution from water.

                   10 = additional uncertainty factor per ODW policy to
                        account for possible carcinogenicity.

Evaluation of Carcinogenic Potential

     0  Data on an increased incidence of lung tumors (adenomas and carci-
        nomas) in 020 strain mice  (Ponomarkov and Tomatis, 1978) were used
        for the quantitative assessment of cancer risk due to styrene.
        Based on the data from this study and using the linearized
        multistage model, a carcinogenic potency factor (qi*) for humans of
        1.34 (mg/kg/day)~1 was calculated from the data for male mice and a
        q1 * of 2.47 (mg/kg/day)~1 was calculated from the data for female mice
        (Ponomarkov and Tomatis, 1978).  Because the data cannot accommodate
        a tumor incidence of 100% when only a single dose is tested, the
        tumor response for female mice was adjusted from 32/32 and the
        transformed dose reduced by multiplying the calculated transformed
        dose, 25.7 mg/kg/day, by the ratio 31/32 to arrive at an adjusted
        transformed dose of 24.9 mg/kg/day.  The higher of the two q-,* values
        is the basis for the estimation of cancer risk levels.  The doses
        corresponding to increased lifetime cancer risks of 10~4, 10~5 and
        10-6 for a 70-kg adult are 3 x 10~3, 3 x 10~4, 3 x 10~5 mg/kg/day,
        respectively.  Assuming a water consumption of 2 liters/day, the
        corresponding concentrations of styrene in water are 1.4, 1.4 x  10~1
        and 1.4 x 10~2 ug/L, respectively.  These criteria, which reflect
        lifetime exposure, are uncertain because of short exposure duration
        (13% of lifetime) and the  small number of animals in each dose group.

      0  IARC evaluated styrene -in  February of 1979 and found insufficient
        evidence to reach a conclusion as to its carcinogenicity rating
        (IARC, 1979).

      •  Applying the criteria described in EPA's guideline for assessment of
        carcinogenic risk (U.S. EPA, 1986), styrene may be classified in
        Group C: Possible human carcinogen.  This category is for agents with
        limited evidence of carcinogenicity in animals in the absence of human

      Styrene                                                          March 31, 1987



           0  The OSHA Standard for styrene is an 8-hour TWA concentration of 100 ppm,
              a ceiling concentration of 200 ppm and a maximum peak concentration
              (29 CFR 1910.1000; Table Z-2) of 600 ppm for 5 minutes or less in any
              3-hour period.

           0  The ACGIH (1982) has established the TWA-TLV for styrene in workroom
              air as 50 ppm with an STEL of 100 ppm.  The TLV was reduced from 100
              ppm in 1981  (ACGIH, 1981).

           0  NIOSH (1983) recommended a styrene concentration limit in workplace
              air of 50 ppm TWA for up to a 10-hour day, 40 hour work-week and a
              ceiling concentration 100 ppm determined during any 15 minute sampling


           0  Styrene content is determined by a purge-and-trap gas chromatographic
              procedure used for the determination of volatile aromatic and unsat-
              urated organic compounds in water (U.S. EPA, 1985b).  This method
              calls for the bubbling of an inert gas through the sample and trapping
              styrene on an adsorbant material.  The adsorbant material is heated
              to drive off styrene onto a gas chromatographic column which is
              temperature  programmed to separate the method analytes which are then
              detected by"the photoionization detector.  This method is applicable
              to the measurement of styrene over a concentration range of 0.05 to
              1,500 ug/L,   Confirmatory analysis for styrene is by mass spectrometry
              which has a  detection limit of 0.3 ug/L (U.S. EPA, 1985c).


           0  Information  is available on the removal of styrene from water by air
              stripping, adsorption and oxidation.  Styrene has a Henry's Law
              Constant of  12 atm which makes it suitable for removal from water by
              air stripping (U.S. EPA, 1985d).
           8  Decarbonaters which have some aeration function have been evaluated
              for their efficacy in styrene removal.  When the influent styrene
              concentration was 0.076 ug/L, the decarbonators tested were able to
              remove 51.3% (U.S. EPA, 1985d).

           0  Tests evaluating adsorption of styrene by granular activated carbon
              showed that  an average of 40% was removed over a 10-month period
              (U.S. EPA, 1985d).  The influent styrene concentration was 0.03 ug/L.

           0  The ethenyl  double bond found in the styrene molecule makes it amend-
              able to oxidation.  It is,  therefore,  possible that oxidative tech-
              niques may be effective in removing styrene from potable water.  Bench
              scale evaluations of ozone treatment of styrene-contaminated water
       •:       conducted by Avigne (1983,  as cited by U.S. EPA,  1985b)  indicate
              that the reaction rate constant for a 0.007 mM styrene solution (pH
              2)  is 300,000 L/mole-sec.  The pH was maintained at 2 to inhibit the

Styrene                                                          March 31,  1987


        decomposition of ozone.  Oxidation of styrene to benzaldehyde and
        hydrogen peroxide was reported by Legube (1983,  as cited by U.S. EPA,
        1985b).  Using an ozone application rate of 10'  mg/hr at 12 L/hr
        0.9 moles ozone per mole of styrene was required to completely oxidize
        the styrene.  The initial styrene concentration  was 1.1  x 10~4 mole/L.
        It was suggested that further oxidation of benzaldehyde  to benzoic
        acid might occur.

     0  It is possible that other oxidizing agents such  as permanganate could
        be effective in oxidizing styrene.  However,  no  studies  of tests of
        these alternative oxidizing situations were available.

    Styrene                                                          March 31,  1987



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Styrene                                                          March 31, 1987

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Styrene                                                          March 31, 1987

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