820K87128            *"* 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.

    p-Dioxane                                              March 31, 1987

         This Health  Advisory  is based upon information presented in the Office
    of Drinking Water's Health Advisory Document for p-Dioxane (U.S. EPA, 1981).
    The 1981  Health Advisory is available for review at each EPA Regional Office
    of Drinking Water counterpart  (e.g., Water Supply Branch or Drinking Water
    CAS No.   123-91-1
    Structural  Formula
    -           /~\

         c  1,4-Dioxane;  1 , 4-Diethylene dioxide


         0  Solvent for cellulose  acetate, resins, oils and waxes.

    Properties  (Windholtz,  1983,  Verschueren,  1977)

            Chemical formula                C4Hg02
            Molecular weight                88.10
            Physical state                  Colorless liquid
            Boiling point                  101. 1CC
            Melting point                  11.8°C
            Vapor pressure                  30 mm  (20°C)
            Density                        1.033 g/ml  (20°C)
            Solubility                      miscible in water at all concentrations
            Taste/odor  threshold


         0  1,4-Dioxane is  a  synthetic organic compound with no known natural
            sources.  Production of  dioxane in  1979 was 6 million Ibs.

         0  Based upon  dioxane 's physical properties, it is expected to volatilize
            from soil and surface  waters.  Dioxane also is expected to be mobile
            in soil. No  information on the bi ode gradation of dioxane has been

         0  Dioxane has not been included in Federal and State surveys of drinking
            water supplies.   However, it has been reported to occur in both surface
            and ground  water  (U.S. EPA, 1979).  No information on the occurrence
            of dioxane  in food  or  air has been identified.

     p-Dioxane                                              March  31,  1987




          0  Oioxane has  been reported  to be  absorbed  readily  through  the lungs,
             skin and gastrointestinal  tracts of mammals.

          0  There is evidence that dioxane is absorbed after  ingestion.   Several
             investigators  administered dioxane in water to rats  and observed
             systemic adverse health effects  (Argus et al.,  1965; Hoch-Ligeti
             et al., 1970;  Kociba  et al.,  1974).  However,  the quantities absorbed
             following ingestion are not known.   Based on the  physico-chemical
             properties of  this compound,  and for the  purpose  of  HA estimation,
             100% absorption  will  be assumed  after ingestion.


          0  Woo et al. (1977b) studied the binding of H3-dioxane to tissue
           .  macromolecules of animals.  Male Sprague-Dawley rats,  weighing  95  to
             130 g,  were  administered a single intraperitoneal dose of  H^-dioxane
             at 500 uCi/100 g body  weight, and sacrificed after 1,  2,  6 or 16
             hours.  Cystolic, microsomal, mitochondrial and nuclear fractions
             were examined.  The percent covalent binding was  highest  in  the
             nuclear fraction followed  by  mitochondrial and microsomal  fractions
             and the whole  homogenate.   The binding of dioxane to the macromolecules
             in the cytosol was mainly  noncovalent. Pretreatment of rats with
             inducers of  microsomal enzymes had  no significant effect  on  the
             covalent binding of dioxane to the  various subcellular fractions of
             the liver.


          0  Oioxane has  been reported  to be  metabolized in animals to  2-hydroxy-
             ethoxyacetic acid and  1,4-dioxan-2-one.   After a  single oral dose  of
             1,000 mgAg  t>w of 1,4-(14C)dioxane  to rats, Braun and  Young  (1977)
             recovered from the urine 85% of  the dose  as  -hydroxyethoxyacetic
             acid (HEAA)  and  most  of the remainder as  unchanged dioxane.   Woo et  al.
             (1977a)  isolated and identified  p-dioxane-2-one from the urine  of
             rats given intraperitoneal doses of 100 to 400 mg dioxane/kg body
             weight;  the  amount of  p-dioxane-2-one excreted increased with the
             dose level administered.

          0  Humans  exposed to 50 ppm dioxane for six  hours eliminated  it from  the
             body primarily by metabolism to  HEAA,  which was subsequently eliminated
             rapidly  in the urine  (Young et al., 1977).

            The  lowest oral lethal dose for humans has been recorded  as  500 mg/kg
             (NIOSH,  1978).

p-Dioxane                                               March 31, 1987

        Johnstone (1959) described a fatal case of dioxane poisoning.  The
        estimated exposure by inhalation in this case was 470 ppm (1,690 mg/m3)
        for one week; the extent of dermal exposure was not known.  Postmortem
        examination revealed hepatic and renal lesions as well as demyelination
        and edema of the brain.
Short-term Exposure
        Oral LD50 values for experimental animals are 4200 mg/kg (rat), 5700
        mg/kg (mouse), 2000 mg/kg (cat), 2000 mgAg (rabbit) and 3150 mg/kg
        (guinea pig)  (NIOSH, 1978).

        Fairley et al. (1934) intravenously injected four rabbits with a
        single dose of either 1, 2, 3 or 5 mL of 80% dioxane diluted with
        saline to a total volume of 10 mL.  Three other rabbits each were
        given two 5 mL intravenous injections of dioxane mixed with 5 mL of
        saline with an interval of 48 hours between injections.  One rabbit,
        used as a control, received TO mL of saline.  The immediate effect of
        dioxane injection in all of the rabbits was violent struggling, which
        began as soon as the first few drops were injected.  With doses of
        4 or 5 mL dioxane, the struggling was followed by convulsions and
        collapse; the rabbits then rapidly returned to normal.  The four
        rabbits given the single doses of 80% dioxane were killed 1 month
        later.  Degeneration of the renal cortices with hemorrhages was
        observed by microscopic examination.  In the rabbit administered the
        3 mL dioxane dose, the degenerative changes extended into the medulla
        and the liver showed extensive cellular degeneration starting at the
        periphery of the lobules.  No abnormality was found in other organs.
        The livers of the rabbits given the 1- and 5 mL doses showed no
        microscopic abnormalities; areas of cloudy swelling were seen in the
        liver of the rabbit given 2 mL of dioxane.
Longer-term Exposure

     0  Kociba et al. (1974)  reported liver and kidney  damage in male and
        female Sherman strain rats.  The animals were given drinking water
        containing 0, 1.0,  0.1  or 0.01% dioxane for up to 716 days.  Toxico-
        logical analysis included changes in body weights, survival rates,
        blood chemistry  (packed cell volume,  total erythrocyte count, hemo-
        globin, total and differential white blood cell counts) and complete
        nistopathological examination.  There was no evidence of toxicity with
        regard to the tested  parameters in animals receiving 0.01% dioxane in
        drinking water;  however,  liver and kidney damage was observed at 0.1%
        dosage level.  Decrease in body weight gains, survival rates, water
        consumption and  an increase in the incidence of tumors (hepatocellular
        and nasal carcinomas) was observed at 1% dosage level.

Reproductive Effects

     0  No reports were  available on the reproductive effects of 1,4-dioxane
        in humans or other mammalian species.

p-Dioxane                                               March 31, 1987


Developmental Effects

     e  No reports were available on the developmental effects of 1,4-dioxane
        in humans or other mammalian species.


     0  No reports were available on the mutagenic potential of 1,4-dioxane.


     0  Hoch-Ligeti et al. (1970) and Argus et al. (1973) observed a linear
        relationship between the total dose of 1,4-dioxane in drinking water
        and the incidence of liver neoplasms in rats.  The levels of 1,4-
        dioxane in the drinking water were 0.75, 1.0, 1.4 and 1.8% for 13
        months.  A minimum effective tumor dose (105), 50% tumor dose (TDso),
        and maximum effective dose (1095) were calculated for 1,4-dioxane.
        These were 72, 149 and 260 g, respectively.

     0  In a two-year study in Sherman strain rats (60/sex/level) given
        1,4-dioxane in drinking water, Kociba et al. (1974) reported that the
        group receiving 1% 1,4-dioxane (calculated to be equivalent to approxi-
        mately 1015 mg/kg/day and 1599 mg/kg/day for male and female rats,
        respectively) showed a significant increase compared to controls in
        the incidence of hepatocellular carcinomas and squamous cell carcinomas
        of the nasal cavity.  At 0.01% (9.6 and 19.0 mg/kg/day, respectively
        for males and females) and 0.1% (94.0 and 148.0 mg/kg/day, respec-
        tively),  there was no significant difference in the incidence of
        neoplasms between the control and the experimental groups.

     0  In a 90-week study in B6C3Fi  mice (50/sex/level) on the oncogenic
        effects of reagent-grade 1,4-dioxane in drinking water, a significant
        increase in hepatocellular carcinomas over controls was reported in
        both the 0.5 and 1% groups of both sexes (NCI, 1978).  The average
        daily low dose (0.5% v/v) was 720 (530 to 990) mg/kg/day for males
        and 380 (180 to 620) mg/kg/day for females; at the 1% level, the
        doses were 830 (680 to 1150)  and 860 (450 to 1560) mg/kg/day,

     0  In the NCI (1978)  study,  Osborne-Mendel rats (35/sex/level)  exposed
        to 1,4-dioxane in drinking water exhibited a dose-related, statisti-
        cally significant incidence of squamous cell carcinomas of the nasal
        turbinates in both sexes.  Hepatocellular adenomas were observed in
        female Osborne-Mendel rats at both dose levels.  Average doses for
        110 weeks for males were 240 (130 to 380)  and 530 (290 to 780) mgAg
        body weight; for females, the doses were 350 (200 to 580) and 640
        (500 to 940) mg/kg body  weight.

Effects on Inununolqgic Status and Competence

     0  Thurman et al. (1978) reported on the in vitro effects of 1,4-dioxane
        on the mitogenic stimulation of murine lymphocytes.  At 2.5 and 5
        g/L,  1,4-dioxane greatly  enhanced lipopolysaccharide stimulation of

   p-Dioxane                                               March 31,  1987

           lymphocytes as well as depressing phytohemagglutinin stimulation of
           lymphocytes.  These results were interpreted to indicate stimulation
           of B-cell proliferation and suppression of T-cell responses.  The
           authors did not discuss the implications of the results in human
           lymphocytes which appeared to be opposite to the findings with murine
           lymphocytes.  In vitro, at 25 g/L of 1,4-dioxane, a slight enhancement
           of phytohemagglutinin stimulation of human lymphocytes was seen, indi-
           cating a stimulation of T-cell responses and an enhancement of the
           immune response; little or no effect was seen at lower concentrations.
           More data confirming this initial finding in murine lymphocytes are
           necessary before any valid conclusions can be made on the immuno-
           suppressive effects of 1,4-dioxane.


        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)  = _   „  ( _   /L)
                        ( UF ) x ( _ L/day )
           NOAEL or LOAEL = No- or Lowest-Observed-Adverse-Ef feet-Level
                            in mg/kg bw/day .

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

                       UF = uncertainty factor (10,  1 00 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

        A study  by  Fairley et  al.  (1934)  has been selected for calculating a  One
   day HA.   In this study, a single dose  of 1 , 2, 3 or 5 mL of 1,4-dioxane was
   given intravenously  to rabbits.   Even  though one rabbit was used per dose
   level, the dose-response data generated by  this  study provide more useful
   information concerning the  toxic effects of dioxane than the other available
   studies.  Rabbits sacrificed one month later had degeneration of the renal
   cortices with hemorrhages as observed  by microscopic examination.  With the
   increasing dose levels, the degenerative change  extended into the medulla
   and the  liver also showed extensive and gross cellular degeneration.

                                                        March 31, 1987
     A One-day HA for a 10 kg child is calculated as follows:
LOAEL (mg/kg/day)

                     (1 ml/day) (1.03 g/ml)  (0.80)  (1000 mg/g)
412 mg/kg/day
        1 ml/day  • Administered dose of p-dioxane  (LOAEL)

        1.03 g/ml « Density of dioxane

        0.80      * Percent composition of dioxane  solution

        1000 mg/g » Conversion factor for grains to  milligrams

        2 kg      • Assumed body weight of rabbit

         One-day HA = (412 mg/kg/day) (10 kg) = 4.12 mg/L (4,120 ug/L)
                         (1 L/day) (1,000)

        412 mg/kg/day = LOAEL for liver and kidney  effects in the rabbit

              10 kg   = Assumed weight of a child

              1 L/day = Assumed volume of water consumed daily by a child

              1,000   = uncertainity factor, chosen in accordance with NAS/ODW
                        guidelines for use with a LOAEL from an animal study.

Ten-day Health Advisory^

     In the absence of an acceptable study for the  calculation of a Ten-day
HA, the One-day HA value is divided by ten; therefore, the Ten-day HA is
estimated as 0.412 mg/L (412 ug/L).

Longer-term Health Advisory

     No suitable data are available to determine a  Longer-term HA.  Kociba
et al. (1974) observed a no effect level of 9.6 mg/kg/day based on a two-year
drinking water study in rats.  This study, although scientifically sound,
should not be used for estimating a Longer-term HA  because of the carcinogenic
potential of p-dioxane.  p-Dioxane has been reported to be carcinogenic in
both sexes of rats and mice by several independent  investigators.  This may
be compared with trichloroethylene where only one species responded to the
carcinogenic effects of the chemical.  Another reason for not calculating a
Longer-term HA for dioxane is its potential of being chlorinated in water,
thus producing a highly toxic chemical.  Woo et al. (1980) showed that
chlorination of dioxane increased the toxicity by as much as 1,000 fold.

p-Dioxane                                               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.

     Because of its suspected carcinogenicity, a Lifetime Health Advisory for
p-dioxane is not recommended.

Evaluation of Carcinogenic Potential

     0  A number of studies show that p-dioxane is carcinogenic in more than
        one animal species.

     0  IARC has classified 1,4-dioxane in  Group 2B, indicating sufficient
        evidence of its carcinogenicity in  animals (IARC, 1982).

     0  Applying the criteria described in  EPA's guidelines for assessment
        of carcinogenic risk (U.S. EPA, 1986), p-dioxane may be classified
        in Group B2:   probable human carcinogen.  This category is for
        agents for which there is inadequate evidence from human studies
        and sufficient evidence from animal studies.

     0  Drinking water concentrations estimated by EPA to increase the risk
        by one excess cancer per million (10~6)  would be 7 micrograms per
        liter, assuming consumption of 2 liters of water per day by a 70-kg
        adult over a 70-year lifetime and using the linearized multistage
        model.  The drinking water concentrations associated with a risk of
        10-4 and 10-5 would be 700 and 70 ug/L,  respectively.

     0  The linearized multistage model is  only  one method of estimating car-
        cinogenic risk.   Using the 10~6 risk level, the following comparisons
        in micrograms/L can be made:   Multistage,  7;  Logit,  10~7;  and Weibull,

      p-Dioxane                                               March  31,  1987


              10-7.  Each model is based on differing assumptions.   No current
              understanding of the biological mechanisms of carcinogenesis is able
              to predict which of these models is more accurate than another.

           0  While recognized as statistically alternative approaches,  the range
              of risks described by using any of these modelling approaches 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 cancer
              risk, the Agency has recommended use of the linearized multistage


           0  NIOSH has recommended an exposure standard of 1 ppm/30 M in air
              (NIOSH, 1977).

           0  TLV = 25 ppm; STEL = 100 ppm (ACGIH,  1980).


           0  There is no standardized method for the determination  of p-dioxane
              in drinking water.  However, p-dioxane can be determined by the purge
              and trap gas chromatographic-mass spectrometric (GC-MS) procedure
              used for determination of volatile organic compounds in industrial
              and municipal discharges (U.S.  EPA,  1984).  In this method, a 5 mL
              water sample is spiked with an internal standard of an isotopically
              stable analog of p-dioxane and  purged with an inert gas.   The volatile
              compounds are transferred from the aqueous phase into  the gaseous
              phase where they are passed into a sorbent column and trapped.   After
              purging is completed, the trap is backflushed and heated to desorb
              the compounds on to a gas chromatograph (GC).  The compounds are
              separated by the GC and detected by a mass spectrometer (MS).  The
              labeled compound serves to correct the variability of the analytical
              technique.  The method detection limit is dependent upon the nature
              of interferences.


           0   Treatment technologies which are capable of  removing p-dioxane  from
              drinking water include adsorption by granular activated carbon  (GAC) or
              powdered activated carbon (PAC).  The only data available demonstrating
              removal of p-dioxane are for carbon  adsorption.  Further studies are
              required to determine the effectiveness of 03 or 03-UV oxidation.
              The available adsorption data are from laboratory bench-scale studies.
              Field pilot studies or plant-scale data on p-dioxane are not available.

           0   McGuire et al.  (1978)  developed isotherms for a number of organic
              chemicals,  including dioxane.   Based  on the  isotherm data,  they
              reported  that the  activated carbon Filtrasorb® 400 exhibited adsorptive

p-Dioxane                                               March 31, 1987

        capacities of 0.6 mg dioxane/g carbon and 3.5 mg dioxane/g carbon at
        equilibrium concentrations of 1  mg/L and 10 mg/L.  They also tested
        the effectiveness of PAC treatment at 50 mg/L with 5-hour contact
        time.  The results showed poor removal efficiency.  However, it was
        concluded that greater removal of 1,4-dioxane could be achieved using
        PAC at higher dosages.

        Suffet et al. (1978) used a pilot-scale test column packed with an
        experimental polymeric resin and compared its performance to granular
        activated carbon.  The resins showed poor performance with respect
        to p-dioxane removal.

        A batch laboratory study to demonstrate oxidation of p-dioxane by 100
        mg/L chlorine and 100 mg/L permanganate showed no reductions after
        12-hour and 3-hour contact times, respectively (McGuire et al.,
        1978).  A batch laboratory study showed diffused aeration to be
        ineffective, achieving less than 3% removal at an 80:1 air-to-water
        ratio over a 2.4-hour period (McGuire et al., 1978).

        Treatment technologies for the removal of 1,4-dioxane from drinking
        water have not been extensively  evaluated (except on an experimental
        level).  An evaluation of some of the physical and/or chemical
        properties of 1,4-dioxane indicates that the following techniques
        would be candidates for further  investigation:  adsorbtion by activated
        carbon and oxidation by O2one or ozone/ultraviolet light.  Individual
        or combinations of technologies  selected to attempt 1,4-dioxane
        reduction must be based on a case-by-case technical evaluation, and
        an assessment of the economics involved.

    p-Dioxane                                               March 31, 1987



    ACGIH.   1980.   American Conference of Governmental Industrial Hygienists.
         Documentation of the threshold limit values.  4th ed.  Cincinnati, OH.
         pp.  154-155.

    Argus,  M.F.,  J.C.  Arcos and C. Hoch-Ligeti.  1965.  Studies on the carcino-
         genic activity of protein-denaturing agents:  Hepatocarcinogenicity of
         dioxane.   J.  Nat. Cancer Inst.  35:949-958.

    Argus,  M.F.,  R.S.  Sohal, G.M. Bryant, C. Hoch-Ligestx and J.C. Arcos.  1973.
         Dose-response and ultrastructural alterations in dioxane carcinogenesis.
         Influence of  methylcholanthrene on acute toxicity.  Eur. J. Cancer.

    Braun,  W.H.  and J.D.  Young.  1977.  Identification of   -hydroxyethoxyacetic
         acid as  the major urinary metabolite of 1,4-dioxane in the rat.  Toxicol.
         Appl.  Pharmacol.  39:33-38.

    Fairley,  A.,  E.G.  Linton and A.H.  Ford-Moore.  1934.  The toxicity to animals
         of 1,4-dioxane.   J. Hyg.  34:486-501.

    Hoch-Ligeti,  C., M.F. Argus and J.C. Arcos.  1970.  Induction of carcinomas
         in the nasal  cavity of rats by dioxane.  Brit. J. Cancer.  24(1):164-167.

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

    Johnstone, R.T.  1959.  Death due  to dioxane?  AMA Arch. Ind. Health.

    Kociba, R.J.,  S.B. McCollister, C. Park, T.R. Torkelson and P.J. Gehring.
         1974.  1,4-Dioxane.  I.  Results of a 2-year ingestion study in rats.
         Toxicol.  Appl.  Pharmacol.  30(2):275-286.

    McGuire,  M.J., I.H.  Suffet and J.V. Radziul.  1978.  Assessment of unit
         processes for the removal of  trace organic compounds from drinking water.
         JAWWA.   10:565-572.

    NCI.   1978.   National Cancer Institute.   Bioassay of 1,4-dioxane for possible
         carcinogenicity.  Washington, D.C.:  U.S.  Department of Health, Education
         and  Welfare,  National Institute of Health.  DHEW Pub. No. (NIH) 78-1330.

    NIOSH.   1977.   National Institute  of Occupational Safety and Health.  Criteria
         for  a recommended standard — occupational exposure to dioxane.  Washing-
         ton,  D.C.: U.S. Department of Health, Education and Welfare.  DHEW
         (NIOSH)  Pub.  77-226.

    NIOSH.   1978.   National Institute  of Occupational Safety and Health.  Registry
         of toxic  effects of chemical  substances.  U.S. Department of Health,
         Education and Welfare.  Washington, D.C.

p-Dioxane                                                March  31,  1987

Suffet, I.H., L. Brenner, J.T. Coyle and P.R.  Cairo.   1978.   Evaluation of
     the capability of granular activated carbon  and  XAD-2 resin to remove
     trace organics from treated drinking water.   Environmental  Science and
     Technology.   1(12):1315-1322.

Thurman, G.B., E.G. Simms,  A.L. Goldstein and  D.J. Kilian.   1978.   The
     effects of organic compounds used in the  manufacture  of plastics on the
     responsivity of murine and human lymphocytes.  Toxicol.  Appl.  Pharmacol.

U.S. EPA.  1979.  U.S.  Environmental Protection Agency.  Chemical Hazard
     Information Profile: Dioxane, Office of Toxic Substances.

U.S. EPA.  1981.  U.S.  Environmental Protection Agency.  Health  advisory
     document for p-dioxane.  Draft.  Office of Drinking Water.

U.S. EPA.  1984.  U.S.  Environmental Protection Agency.  Method  1624 Revision
     B, Volatile Organic Compounds by Isotope  Dilution GC/MS.  Federal Register.

U.S. EPA.  1986.  U.S.  Environmental Protection Agency.  Guidelines  for
     carcinogenic risk assessment.  Fed. Reg.  51(185):33992-34003.
     September 24.

Verschueren, K.  1977.   Handbook of environmental  data on  organic chemicals.
     1st ed.  Van Nostrand  Reinhold Company, N.Y.  p.  377.

Windholz, M., ed.  1983.   Merck Index, 10th ed.  Merck and Company,  Inc.
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