March 31, 1987
                         820K87012
                                  ETHYLENE GLYCOL

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

        The Health Advisory (HA)  Program,  sponsored  by  the  Office  of Drinking
   Water (ODW), provides information on the health effects,  analytical Tiethod-
   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 oE  the
   population.

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

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

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         This Health Advisory is  based upon information presented in the Office
    of Drinking Water's Health Advisory Document for Ethylene Glycol (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 Branch).
II.  GENERAL INFORMATION AND PROPERTIES

    CAS No.   107-21-1

    Structural Formula

                                    CH2-OH

                                    CH2-OH

    Synonyms

            1,2-e thanediol

    Uses

         0  Antifreeze  in cooling and heating systems,  industrial humectant,
            ingredient  of electrolytic condensers,  solvent in paint and plastic
            industries  and in the formulation of ink.

    Properties  (Verschueren, 1977;  Windholz, 1983)

            Chemical Formula                C2H62
            Molecular Weight                62.1
            Physical State                  colorless  liquid
            Boiling Point                   197.6C
            Melting Point                   -12.6C
            Density
            Vapor Pressure                  0.05 mm (20C)
            Specific Gravity                1.113 (20C)
            Water Solubility                completely miscible
            Log Octanol/Water Partition
              Coefficient
            Taste Threshold
            Odor Threshold
            Conversion  Factor
    Occurrence
            In 1983, 4.5 billion pounds of ethylene glycol were produced (U.S.
            ITC,  1984).  The majority of ethylene glycoL is used consumptively
            (CEH, 1983).

            Releases of ethylene glycol to the environment can occur during pro-
            uction, use and release.  The major source of release is from the
            disposal of used antifreeze.  Releases of ethylene glycol occur

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             largely to water and land during disposal; releases to the atmosphere
             are limited by ethlyene glycol's low vapor pressure.  Releases of
             ethylene glycol to the environment are dispersed widely.

             Ethylene glycol in the environment rapidly partitions to water due to
             its solubility and low vapor pressure.  Releases to surface water are
             biodegraded rapidly.  Releases of ethylene glycol to land have
             resulted in the contamination of ground water (U.S. EPA, 1980).
             Based upon its physical properties, ethylene glycol is not expected to
             bioaccumulate.

             There is little information on the presence of ethylene glycol in
             water,  food and air.  Because of its rapid degradation in the environ-
             ment, ethylene glycol is not expected to be a common contaminant in
             air,  food or surface water; however, contamination of ground water is
             possible.  A more likely source of ethylene glycol exposure is the
             inadvertant contamination of drinking water from the misuse of
             antifreeze.
III.  PHARMACOKINSTICS

     Absorption

          0  Ethylene glycol is absorbed rapidly after ingestion.  Reif (1950),
             on three separate occasions,  drank pure ethylene glycol in 100 ml of
             water.   Amounts consumed were 5.5, 11.0 and 13.2 g, which would corre-
             spond to 78.5,  157 and 188.6  mg/kg, respectively, assuming a body
             weight of 70 kg for an adult.  Ethylene glycol was recovered in the
             urine at 24 to  31% of the administered dose within 24 to 43 hours.
             Oxalic  acid concentrations in the urine were higher than normal with
             a peak  on the fourth day.

     Metabolism

          0  Gessner et al.  (1961) studied the fate of ethylene glycol in Chinchilla
             rabbits, albino rats, guinea  pigs and cats.  Doses up to 10.0 g/kg  of
             ethylene glycol (  02) were given orally or subcutaneously, but most
             of the  data were derived from animals receiving 0.1 to 2.0 g/kg (100
             to 2000 mg/kg).  At low doses (0.124 g/kg), rabbits exhaled about 60%
             of the  dose as  CC>2 and excreted 20% of i t in the urine in a time
             period  of 80 to 100 hours; 50% of the dose was exhaled as COi in the
             first 18 hours  after dosing.   In one set of experiments with rabbits,
             urine contained ethylene glycol (10.3%), oxalic acid (0.01%) and urea
             (0.65%).  Nearly one-half of  the radioactivity was eliminated in the
             urine when the  dose was increased to 2.5 to 5.0 g/kg.  The increase
             in the  radioactivity in the urine was attributed by the authors to
             unmetabolized ethylene glycol.

          0  In an in vitro  experiment utilizing rat liver slices, Gessner et al.
             (1961)  identified the intermediate metabolites of ethylene glycol
             (  ^C) as glycoaldehyde and glyoxylic acid.

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IV. HEALTH EFFECTS
    Humans
            A controlled study of human exposure to ethylene glycol was reported
            by Reif (1950).  The investigator drank 5.5, 11.0 and 13.2 g of
            ethylene glycol with 100 ml of water on separate occasions and
            collected his urine for about 14 days after each trial to quantify
            ethylene glycol and oxalic acid levels.  Assuming a body weight of 70
            kg, doses consumed would be 78.5, 157.0 and 188.6 mg/kg.  Reif found
            that 24 to 31% of the ethylene glycol was excreted in the urine in an
            unchanged form within 24 to 36 hours, while urinary oxalic acid
            levels were elevated for 8 to 12 days.  No oxalate crystals were
            found in the urine, and he reported no impairment of health from
            these doses.

            Ethylene glycol ingestion by humans results in a variety of CMS/
            behavioral effects including numbness, visual disturbances,  light-
            headedness, headache and lethargy (Herman et al., 1957), with doses
            estimated at 1,000 mg/kg.  After ingesting a dose of approximately
            3,000 mg/kg, patients exhibited ataxia, somnolence and slurred speech,
            followed by disorientation with a mental status alternating between
            stupor and agitation (Parry and Wallach, 1974).  At doses which were
            eventually fatal, coma developed after a period of restlessness,
            delerium, convulsive seizures and a loss of reflexes (Pons and Custer,
            1946).  These same symptoms of ataxia, incoordination, somnolence,
            coma and eventual death have been reported in dogs (Nunamaker et al.,
            1971 ).
    Animals
    Short-term Exposure
            An extensive series of dose-mortality trials were conducted by L,aug
            et al. (1939) for several species of laboratory animals*  Mice, rats
            and guinea pigs were tested by administering single doses of ethylene
            glycol by stomach tubes.  Calculated LDso values were:  mice, 13.1
            ml/kg (14,253 mg/kg); rats, 5.5 ml/kg (5,984 mg/kg); guinea pigs,
            7.35 ml/kg (7,997 mg/kg).  It was noted that the animals showed signs
            of weakness and lack of motor coordination shortly after receiving
            doses of ethylene glycol.  Prostration and coma were later symptoms,
            followed by death in 18 hours to 6 days.  Congestion of the lungs,
            bladders filled with protein rich urine, hydropic degeneration of the
            cells lining the cortical convoluted tubules, and focal necrosis of
            the liver were nearly always found.
            NIOSH (1983-84) lists the following oral LD^g data for ethylene glycol:
            rat (4,700 mg/kg), mouse (7,500 mg/kg), guinea pig (6,610 rug/kg).
    Long-term Exposure
            In a study by Blood et al.  (1962) ethylene glycol was fed  to  two male
            rhesus monkeys and one female Rhesus monkey for three years.  Ethyleno

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        glycol was incorporated in the monkey chow and made available to  the
        animals on an ad lib basis.  The animals consumed 200 to  250 g of
        chow/day.  From the given body weights of 15.45 and 7.25  kg for the
        males and 7.4 kg for the female, the amount of ethylene glycol consumed
        would range from approximately 25 to 69 mg/kg/day for males and 135
        to 170 mg/kg/day for females.  Prior to the start of the  experiment,
        and at quarterly intervals, the animals were x-rayed to detect the
        possible appearance of calcification of the urinary tract.  At the
        time of sacrifice all abdominal and endocrine organs, as  well as a
        bone marrow sample, were examined histopathologically.  No abnormal
        calcium deposits were demonstrated by x-ray; microscopic  examinations
        of tissues were unremarkable.  The authors concluded that this species
        was capable of handling the administered ethylene glycol  without any
        discernible toxic effects.

        In a study by Blood (1965), ethylene glycol was fed to groups of 16
        male and 16 female Sprague-Dawley rats for 2 years at concentrations
        of 0.0, 0.1, 0.2, 0.5, 1 or 4% by weight in the diet (corresponds to
        approximately 0, 50, 100,  250, 500 or 2,000 mg/kg/day (Lehman, 1959)).
        Increased mortality appeared in males receiving the 1 and 4% diets.
        Calcification of the kidneys and oxalate-containing calculi were
        observed in males at doses of 0.5% and greater.  Females  were similarly
        affected at the 1% level and greater for calcification and at the 4%
        level for calculi.  Increased water consumption and protein in the
        urine was evident in males at both 1 and 4% and in females at 4% diet
        levels.  A probable NOAEL of 0.2% was determined (approximately 100
        mg/kg/day) and a LOAEL of  0.5% (approximately 250 mg/kg/day).

        A recently completed toxicity study in groups of 130 Fischer 344 rats
        per sex per level fed ethylene glycol at dosages of approximately
        1.0, 0.2, 0.04 or 0.0 g/kg/day for up to 2 years (DePass  at al.,
        1986a) identified a NOAEL  of 0.04 g/kg/day (40 mg/kg/day).  The
        mortality rate was increased in the high-dosed males with all dead by
        475 days into the study.  Oxalate neohrcsis was the primary cause of
        death.  Other effects noted in the high-dosed males only  included:
        reduced body weight gain,  increased water intake,  increased 3'JtI and
        creatinine, reduced RBCs,  hematocrit and hemoglobin, increased
        neutrophil count, increased urine volume and reduced urinary specific
        gravity and pH.  Additionally, all high-dosed rats had increased
        kidney weights and urinary calcium oxalate crystals.  High-dosed
        females also showed the presence of uric acid crystals in the urine.
        Histopathological changes  in the high-dosed males included tubular
        cell hyperplasia, tubular  dilation and peritubular nephritis.  At the
        next lower dose, 0.2 g/kg/day, an increase in incidence and anoant of
        calcium oxalate crystals was evident in both sexes.  It is apparent
        in this study that the male rat is more sensitive to the  effects of
        ethylene glycol.

        These same authors treated 80 CD-1 mice per sex per level to the
        same concentrations of ethylene glycol in the diet and' found no
        clinical or histopathological evidence of toxicity attributable to
        its intake.

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Reproductive Effects

     0  Timed-pregnant CD rats were dosed by gavage on days 6 through 15 of
        gestation with ethylene glycol at 0, 1,250, 2,500 or 5,000 mg/kg/day
        (Price et al., 1985).  No maternal deaths or distinctive clinical
        signs were noted.  Significant decreases in maternal weight were dose-
        related in rats at all levels.  Other significant changes  included
        reduced gravid uterus weight,  corrected gestational weight gain
        and reduced fetal body weight per litter at the mid and high doses
        and increases in post-implantation losses per litter, significant
        only at the high dose.  This study established a LOAEL of  1,250
        ing/kg/day for maternal effects and a NOAEL of 1,250 mg/kg/day for
        fetal effects.

     0  Timed-pregnant CD-1  mice were dosed by gavage on days 6 through 15 of
        gestation with ethylene glycol at 0, 750, 1,500 or 3,000 mg/kg/day
        (Price et al., 1935).  No maternal deaths or distinctive clinical
        signs were noted.  Significant decreases in maternal weight, gravid
        uterus weight and corrected gestational weight gain were evident at
        the mid and high doses.  Fetal body weight per litter was  also signifi-
        cantly reduced at all doses.  This study established a NOAEL of 750
        mg/kg/day for maternal effects and a LOAEL of 750 mg/kg/day for fetal
        effects.

     0  In a continuous breeding study, Lamb et al. (1985) dosed CD-1  nice
        with ethylene glycol by continuous administration in drinking water
        at 0.0, 0.25, 0.5 or 1%.  Slight but statistically significant
        decreases were found in the numbers of litters per fertile pair
        (p <0.01), live pups per litter (p <0.05) and mean live pup weight
        (p <0.01) at the 1% level when compared to Fg controls.  No clinical
        signs of  toxicity or significant adverse effects on body weight or
        water consumption were seen in this study but two deaths at the 0.5%
        level may have been related to oxalate crystal deposition.  This
        study established a NOAEL for reproductive effects of 0,5% (w/'v) in
        drinking  water.  (Between days 98 and 105 on the study, this level
        corresponded to an average daily intake of 0.84 g/kg.)

     0  In a three-generation reproduction study, DePass et al. (1986b) fed
        ethylene  glycol to Fischer 344 rats at levels of approximately 1.0,
        0.2, 0.04 or 0.0 g/kg/day.  No evidence of reduced fertility or
        increased fetal death was observed in any groups receiving the test
        diet.  This study established a NOAEL for maternal and fetal effects
        at 1,000  mg/kg/day (highest dose tested).

Developmental Effects

     0  Lamb et al. (1985),  in a continuous breeding study using CD-I  mice,
        administered ethylene glycol on a continuous basis for 126 days at
        levels of 0.0, 0.25, 0.5 or 1% in drinking water.  The final offspring
        of these  continuously bred mice were examined and the authors noted
        facial anomalies in a number of the offspring of the high-dosed mice.
        Examination for skeletal defects demonstrated a pattern including
        reduction in size of the bones in the skull, fused ribs and abnormally

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        shaped sternabrae and vertebrae.  No similar findings were noted at
        the two lower dose levels.  This study established a NOAEL of 0.5%
        (w/v) in drinking water for developmental effects in mice.   (Between
        days 98 and 105, the average daily intake corresponded  to approxi-
        mately 840 mg/kg for the parental generation.)

     0  Administration of ethylene glycol by gavage on days 6 through 15 of
        gestation at levels of 0, 1,250, 2,500 or 5,000 mg/kg/day in rats and
        0, 750, 1,500 or 3,000 mg/kg/day in mice resulted in significant
        increases in the percentage of malformed live fetuses per litter
        and/or the percent of litters with malformed fetuses at all dose
        levels with >95% of the litters affected at the high dose for both
        species.  The most common malformations included craniofacial and
        neural tube closure defects and axial skeletal hyperplasia in both
        species (Price et al., 1985).  This study established a LOAEL of
        approximately 1,250 rng/kg/day in rats and 750 mg/kg/day in mice (the
        lowest levels fed).

iMutagenicity

     0  In a dominant lethal mutagenesis study in rats,  DePass et al.  (1986b)
        bred at weekly intervals the F2 males (fed ethylene glycol in the
        diet at 1.0, 0.2, 0.4 or 0.0 g/kg/day) from a three-generation
        reproduction study to 3 consecutive lots of untreated females.  No
        evidence of reduced fertility or increased fetal death was observed
        in any of the groups receiving ethylene glycol.   This study established
        a NOAEL for mutagenic effects at 1,000 mg/kg/day (highest dose tested).

     0  Ethylene glycol demonstrated no significant mutagenic activity in the
        Salmonella mutagenicity (Ames) test with or without microsomal acti-
        vation (Clark et al., 1979).

Carcinogenici ty

     0  No evidence of an oncogenic effect of ethylene glycol in SO 70-1  mice
        per sex per level or 130 Fischer 344 rats per sex per level .;as seen
        when fed in the diet at approximately 1.0,  0.2,  0.04 or 0.0 g/kg/day
        for 24 months.  Mortality of the high-dosed male rats in this study
        was 100% after 475 days of feeding.  Death was attributed to oxalate
        nephrosis (DePass et al., 1986a).

     0  In studies designed to determine the toxic and carcinogenic potential
        of several biological preservatives, ethylene glycol was administered
        subcutaneously at 5 dose levels to groups of 20 weanling Fischer 344
        rats (Mason et al., 1971).  The LD5Q for a single injection was
        5,300 mg/kg.  When given subcutaneously, twice weekly for four weeks,
        the maximum tolerated daily dose was found to be lower  than 1,700
        mg/kg (total dose of 13,600 mg/kg).  In a long-term study, 4 groups
        of 80,  60, 40 and 20 rats were injected subcutaneously  twice weekly
        for 52 weeks with 1,000, 300, 100 and 30 mg/kg,  respectively.  Animals
        were observed for an additional six months following treatment.  In
        these animals, there was no evidence of ethylene glycol toxicity
        based on survival time, weight gain and drug related organ pathology.

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   Ethylene Glycol                                         March 31, 1987
V. QUANTIFICATION OF TOXICOLOGICAL EFFECTS

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

        Data from the study of Reif (1950) were used to identify an oral NOAEL
   in humans.  This investigator drank a 188.6 mg/kg dose of ethylene glycol
   with no discernable effects.  Thus, a One-day HA for children exposed to
   ethylene glycol in drinking water may be calculated as follows:

        For a child:

          One-day HA = (188.6 mg /kg/day )( 1 0 kg) _ 13.86 mg/L (19,000 ug/L)
                           (100) (1 L/day )

   where :

        188.6 mg/kg/day = NOAEL in humans consuming up to this dose in water.

                  10 kg = assumed body weight of a child.

                   - 1 00 = uncertainty factor, chosen in accordance with NAS/ODW
                          guidelines for use with a NOAEL from a human study.
                          An additional factor of 10 has been added for a study
                          with only one subject.

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

   Ten-day Health Advisory

        There are not sufficient data to calculate a Ten-day Health Advisory.
   The Longer-term HA of 5.5 mg/L for the 10 kg child can serve as a conservative

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estimate of an exposure which would be considered adequately protective over
a ten-day exposure period.

Longer-term Health Advisory

     Exposure of male and female Rhesus monkeys to 55 to 170 mg/kg/day ethylene
glycol in the diet for three years caused no adverse response (Blood et al.,
1962).  A Longer-term HA based on these data is calculated as follows:

     For a 10-kg child:

       Longer-term HA = (55 mg/kg/day) (10 kg) = 5>5 mg/L (5'500 ug/L)
where:

        55 mg/kg/day = NOAEL, based on absence of toxic signs in the monkey.

               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.

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

     For a 70-kg adult:

      Longer-term HA = (55 mg/kg/day) (70 kg) = 19<25 mg/L (19,250 ug/L)
                          (100) (2 L/day)

where:

        55 mg/kg/day = NOAEL, based on absence of toxic signs in the monkey.

               70 kg = assumed body weight of an adult.

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

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

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

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water) lifetime exposure level, assuming 100% exposure from that medium, at
which adverse, noncarcinogenic health effects would not be expected to occur.
The DWEL is derived from the multiplication of the RfD by the assumed body
weight of an adult and divided by the assumed daily water consumption of an
adult.  The Lifetime HA is determined in Step 3 by factoring in other sources
of exposure, the relative source contribution (RSC).  The RSC from drinking
water is based on actual exposure data or,  if data are not available,  a
value of 20% is assumed for synthetic organic chemicals and a value of 10%
is assumed for inorganic chemicals.  If the contaminant is classified as a
Group A or B carcinogen, according to the Agency's classification scheme of
carcinogenic potential  (U.S. EPA, 1986), then caution should be exercised in
assessing the risks associated with lifetime exposure to this chemical.

     The study of Blood (1965) is considered most appropriate for calculating
a Lifetime Health Advisory.  In this study rats were fed ethylene glycol in
the diet at concentrations of 0.0, 0.1, 0.2, 0.5, 1, or 4% (approximately 0,
50, 100, 250, 500 or 2,000 mg/kg/day according to Lehman, 1959) for up to two
years.  This study identified a NOAEL of 0.2% (100 mg/kg/day) primarily for
kidney effects in rats.  Using this NOAEL,  the Lifetime HA is calculated as
follows:

Step 1:  Determination of the Reference Dose (RfD)

                     RfD =  (100 mg/kg/day)  = 1 mg/kg/day
                                (100)
where:

        100 mg/kg/day = HOAEL for kidney effects in rats.

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

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

             DWEL = (1 mg/kg/day) (70 kg) = 35 ng/L (35(oOO ug/L)
                          (2 L/day)

where:

        1 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 = (35 mg/L) (20%) = 7 mg/L  (7,000 ug/L)
where:

             35 mg/L = DWEL.

                 20% = assumed relative source contribution from water.

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      Evaluation of Carcinogenic Potential

           0  Applying the criteria described in EPA's guidelines for assessment of
              carcinogenic risk (U.S. EPA, 1986), ethylene glycol may be classified
              in Group D:  Not classified.  This category is for agents with inade-
              quate animal evidence of carcinogenicity.  The study by DePass et al.
              (1986a) was not a definitive indicator for carcinogenicity.  The
              study indicated a difference in time to detection of lymphocarcinomas
              in the female rat.  The incidence of this tumor type was not signifi-
              cantly different.


  VI. OTHER CRITERIA, GUIDANCE AND STANDARDS

           0  ACGIH (1984) has proposed a ceiling limit of 50 ppm (   125 mg/m3)
              for vapor and mist to minimize irritation of respiratory passages.


 VII. ANALYTICAL METHODS
              There is no standardized method for the determination of ethylene
              glycol in drinking water samples.  A procedure has been developed
              (Hartman and Bowman,  1977) to determine the presence of ethylene
              glycol in drugs and pharmaceutical formulations at concentration
              levels of 5-200 mg/L.  This procedure is based on direct aqueous
              injection-gas chromatography of samples.  It is probable that this
              procedure also applies to drinking water samples at concentration
              levels of at least 5 mg/L.
VIII. TREATMENT TECHNOLOGIES
              Ethylene glycol is completely miscible with water (Windholz, 1983)
              and has a low vapor pressure of 1  mmHg at 53C (CRC Handbook of
              Chemistry and Physics,  1982).  These two factors make it impractical
              to consider aeration as a form of  removal.  Treatment with activated
              carbon does not remove  much of this compound from solution either.
              The adsorbability of ethylene glycol is only 0.0136 mg/g carbon with
              only 6.3% ethylene glycol retention (Veschueren,  1977).   No information
              was found on the removal of this compound from drinking  water using
              other techniques.

              Ethylene glycol may contaminate drinking water due to misapplication
              of the chemical as an antifreeze in potable water systems or through
              crossconnections with non-potable  fire protection or heating/cooling
              systems.  In these cases vigorous  flushing of the contaminated compo-
              nents of the distribution system should be sufficient.

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IX.  REFERENCES
    ACGIH.   1984.   American Conference of Governmental Industrial Hygienists.
         Documentation of the threshold limit values.   4th ed.  1980-1984 Supplement.
         pp. 182-183.

    Berman,  L.B.,  G.E. Schreiner and J. Feys.  1957.  The nephrotoxic lesion of
         ethylene  glycol.  Ann.  Int. Med.  46:611-619.

    Blood,  F.R.,  G.A. Elliott and M.S. Wright.   1962.   Chronic toxicity of
         ethylene  glycol in the  monkey.  Toxicol. Appl. Pharmacol.  4:489-491.

    Blood,  F.R.   1965.  Chronic  toxicity of ethylene glycol in the rat.
         Fd. Cosmet.  Toxicol.  3:229-234.

    CEH.  1983.   Chemical Economics Handbook.  Ethylene Glycol. 652.5030.  Stanford
         Research  Institute, Menlo Park, California.

    Clark,  C.R.,  T.C. Marshall,  B.S. Merickel,  A. Sanches, D.G. Brownstein and
         C.H. Hobbs.   1979.  Toxicological assessment of heat transfer fluids
         proposed  for use in solar energy applications.  Toxicol. Appl. Pharmacol.
         51:529-535.

    CRC Handbook  of Chemistry and Physics.  1982.  A Ready-Reference Book of
         Chemical  and Physical Data.  62nd Ed.   Boca Raton, Florida, p. D-175.

    DePass,  L.R.,  R.H. Garman, M.D. Woodside, W.E. Giddens, R.R. Maronpot and
         C.S. Weil.  1986a.  Chronic toxicity and oncogenicity studies of ethylene
         glycol  in rats and mice.  Fund. Appl.  Toxicol.  7:547-565.

    DePass,  L.R.,  M.D. Woodside, R.R. Maronpot and C.S. Weil.  1986b.  Three-
         generation reproduction and dominant lethal mutagenesis studies of
         ethylene  glycol in the  rat.  Fund. Appl. Toxicol.  7:566-572.

    Gessner, P.K., D.V. Parke and R.T. Williams.  1961.  Studies in detoxication 36.
         The metabolism of 14C labelled ethylene glycol.  Biochem. J.  79:432-489.

    Hartman, P.A., and P.B. Bowman.  1977.  Simple GLC determination of ethylene
         oxide and its reaction products in drugs and formulation.  J. Pharm. Sci.
         66:789-792.

    Lamb, J.C.,  IV, R.R. Maronpot, D.K. Gulati, V.S. Russell, L. Homme1-Barnes
         and P.S.  Sabharwal.  1985.  Reproductive and developmental toxicity of
         ethylene  glycol in the  mouse.  Toxicol. Appl. Pharmacol.  81:100-112.

    Laug, E.P.,  H.O.  Calvery, H.J. Morris and G. Woodward.  1939.  The toxicology
         of some  glycols and derivatives.  J. Ind. Hyg. Toxicol.  21:173-201.

    Lehman,  A.J.    1959.  Appraisal of the safety of chemicals in foods, drugs and
         cosmetics.  Association of Food and Drug Officials of the United States.

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Ethylene Glycol                                         March 31,  1987

                                     -13-
Mason, M.M., C.C. Gate and J. Baker.  1971.  Toxicology and carcinogenesis
     of various chemicals used in the preparation of vaccines.  Clin. Toxicol.
     4:185-204.

NIOSH.  1983-84.  National Institute of Occupational Safety and Health.
     Registry of toxic effects of chemical substances.  U.S. Dept.  of Health,
     Education and Welfare, Supplement,  p. 904.

Nunamaker, D.M., W. Medway and P. Berg.  1971.  Treatment of ethylene glycol
     poisoning in the dog.  J. Am. Vet. Med. Assoc.  159:310-314.

Parry, M.F., and R. Wallach.  1974.  Ethylene glycol poisoning.  Am. J. tied.
     57:143-150.

Pons, C.A., and R.P. Custer.  1946.  Acute ethylene glycol poisoning.  A
     clinico-pathological report of eighteen fatal cases.  Am. J. Med. Sci.
     211:544-552.

Price, C.J., C.A. Kimmel, R.W. Tyl and M.C. Marr.  1985.  The developmental
     toxicity of ethylene glycol in rats and mice.  Toxicol. Appl. Pharmacol.
     31 .-113-127.

Reif, G.  1950.  Self-experiments with ethylene glycol.  Pharmazie.  5:276-278,

U.S. EPA.  1980.  U.S. Environmental Protection Agency.  Damages and Threats
     Caused by Hazardous Material Sites.  Oil and Special Materials Control
     Division.  Draft, p. 43.

U.S. EPA.  1981.  U.S. Environmental Protection Agency.  Health Advisory
     Document for Ethylene Glycol.  Draft.  Office of Drinking Water.

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

U.S. ITC.  1984.  U.S. International Trade Commission.  Synthetic Organic
     Chemicals, United States Production and Sales, 1983.  Washington, O.C.
     USITC Publication 1588.

Verschueren, K.  1977.  Handbook of environmental data on organic chemicals.
     New York, NY:   Von Nostrand Reinhold Company, p. 322.

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

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