820K88006                                  August, 198?
             ENDOTHALL

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

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

        Health Advisories are developed  for  one-day,  ten-day, longer-term
   (approximately 7 years, or 10% of  an  individual's lifetime) and lifetime
   exposures based on data describing noncarcinogenic end points of  toxicity.
   Health Advisories do not  quantitatively incorporate any potential carcinogenic
   risk from such exposure.   For  those substances that are known or  probable
   human carcinogens,  according to the Agency classification scheme  (Group A or
   B),  Lifetime  HAs are not  recommended.   The chemical concentration values for
   Group A or B  carcinogens  are correlated with carcinogenic risk estimates by
   employing a cancer potency (unit risk)  value together with assumptions for
   lifetime exposure and  the consumption of  drinking water.  The cancer unit
   risk is usually derived from the linear multistage model with 95% upper
   confidence limits.   This  provides  a low-dose estimate of cancer risk to
   humans that is considered unlikely to pose a carcinogenic risk in excess
   of the stated values.   Excess  cancer  risk estimates may also be calculated
   using the One-hit,  Weibull,  Logrt  or  Probit models.  There is no  current
   understanding of the biological mechanisms involved in cancer to  suggest that
   any one of these models is abne 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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Endothall
                                                                     August,  1987
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II.  GENERAL INFORMATION AND PROPERTIES
    CAS No.   145-73-3
    Structural Formula
                                              COOH
                  7-Oxabicyclo-(2,2, 1 )-heptane-2, 3-dicarboxylic acid
    Synonyms
    0   1 ,2-dicarboxy3,6-endoxocyclohexane;  Aquathol;  Hydrothol;  Des-i-cate,-
        Accelerate

Uses

    0   Endothall is used as a defoliant and an herbicide on both terrestrial
        and aquatic weeds.

Properties  (Carlson et al. , 1978;  Simsiman  et al. ,  1976)

        Chemical Formula
        Molecular Weight
        Physical State (25°C)
        Boiling Point
        Melting Point
        Density
        Vapor Pressure (25°C)
        Specific Gravity
        Water Solubility (25°C)
        Log Octanol/Water Partition     —
          Coefficient
        Taste Threshold
        Odor Threshold                  —
        Conversion Factor               —

Occurrence

     0  No information was found in the available literature on the occurrence
        of endothall.

Environmental Fate

     e  No information was found in the available literature on the environ-
        mental fate of endothall.
                                            186.06
                                            White crystalline solid
                                            —
                                            144°C to the anhydride
                                            —
                                            Negligible
                                            — >
                                            100 g/L (acid monohydrate)

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     Endothall                                                        August, 1987

                                          -3-


III. PHARMACOKINETICS

     Absorption

          0  Few data exist regarding endothall pharmacokinetics in mammals.
             Soo et al.  (1967) performed pharmacokinetic experiments with male
             and female  Wistar rats.   Approximately 82% of a 5-mg/kg oral dose
             of 14c-labeled endothall (dissolved in 20% ethanol to a concentration
             of 1 mg/mL) was absorbed by the rats within 72 hours.  The rats had
             received 5  mg/kg of unlabeled- endothall in the diet for 2 weeks prior
             to treatment with 14c-endothall.

          8  Deaths in rabbits directly exposed to endothall in the eye or on the
             skin (Pharmacology Research, Inc, 1975a, 1975b) indicate the potential
             for absorption by these routes.

     Distribution

          0  In the Soo  et al. (1967) study, the absorbed endothall was distrib-
             uted in low levels through most body tissues.  Peak levels in all
             tissues were observed 1  hour after dosing,  with most of the dose
             (about 95%) found in the stomach and intestine.  Otherwise, the
             tissues with the highest concentrations after 1 hour were the liver
             and kidney  (1.1 and 0.9% respectively), with lower concentrations
             (0.02 to 0.1%) in heart, lung,  spleen and brain.  Very low concentra-
             tions were  observed in muscle,  and endothall was not detected in fat.
             No marked preferential accumulation was apparent.

     Metabolism

          0  The metabolism of endothall is  not known to be characterized.

     Excretion

             Soo et al.  (1967) described excretion as follows:

          0  Clearance of  4C-endothall was  biphasic in the stomach (t1 ,2 = 2-2 and
             14.2 hours) and kidney (t^ » 1.6 and 34.6 hours) and monophasic
             in the intestine and liver (t^  = 14.4 and 21.6 hours, respectively).
             Total excretion of the 14c label was over 95% complete by 48 hours and
             over 99% complete by 72 hours,  suggesting that no significant
             bioaccumulation occurred.

          0  Approximately 90% of the administered dose was excreted in the feces.
             Urinary excretion accounted fbr approximately 7% of the dose, and
             approximately 3% of the radioactive label was recovered in expired
             carbon dioxide.

          0  Approximately 20% of the dose excreted in the feces was unchanged
             endothall.   The remaining radioactivity was presumed to be metabolites
             or conjugates.

          0  Soo et al.  (1967) also found no radioactivity in pups from lactating
             dams given  oral doses of 14c-endothall.

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    Endothall                                                         August,  1987

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IV. HEALTH EFFECTS

    Humans

         0  No information was found in the available literature on the health
            effects of endothall in humans except for one case history of a young
            male suicide victim who ingested an estimated 7 to 8 g of disodium
            endothall in solution (approximately 100 mg endothall ion/kg).
            Repeated vomiting was evident.  Autopsy revealed focal hemorrhages
            and edema in the lungs and gross hemorrhage of the gastrointestinal
            (GI) tract (Allender, 1983).

    Animals

       Short-term Exposure

          0  Early acute studies report cardiac arrest (Goldstein, 1952) or
            respiratory failure  (Srensek and Woodard, 1951) as causes of death
            in dogs and rabbits.  Endothall was injected  intravenously in both
            studies with these effects observed at doses  of 5 mg/kg  (lowest)
            and higher.

          0  The available acute oral- dose studies are essentially restricted  to
            mortality data without biochemical or histopathological  observations.
            The acute toxicity of endothall acid appeared to be  greater than  that
            of the salt forms normally used in herbicide  formulations.  In rats,
            the oral LD50 of  endothall was  reported  as  35 to 51  mg/kg for  the
            acid  form and 182 to  197 mg/kg  for the sodium salt  (Simsiman  et al.,
            1976;  Tweedy and  Houseworth,  1976).

          0  Rats  were given  1,000 or  10,000 ppm  disodium  endothall  in the diet
             (Brieger,  1953a)  and  doses  were calculated  by assuming  a body weight
            of  0.4 kg and daily  food  consumption of  20  g.  Slight liver degeneration
            and  focal hemorrhagic areas  in  the kidney were reported  for male  and
             female rats dosed orally  with approximately 40 mg  endothall ion/kg/day
             for 4 weeks;  most of the  rats receiving  approximately 400 mg  endothall
             ion/kg/day  died  within  1  week.  The  liver and kidney effects  from
             endothall  ingestion  are consistent with  the pharmacokinetic tissue
             distribution  results reported by  Soo et  al. (1967).

          0  Nine male dogs  (one dog/dose)  were do-ed orally with capsules containing
             1 to 50 mg disodium  endothall/kg/day vO.8  to 40 mg endothall  ion/kg/day)
             for 6 weeks (Brieger, 1953b).  All dogs  that were administered 20 to
             50 mg disodium  endothall/kg/day died within 11 days.  Vomiting and  diarrhea
             were observed in the group given  20  mg disodium endothall/kg/day.
             Pathological  changes in the GI tract,  described as congested  and
             edematous stomach walls and edematous  upper intestines,  were  indicated
             as common in  all dogs.   Erosion and  hemorrhages in the stomach were
             observed with doses of  20 mg/kg/day  or more.

        Dermal/Ocular Effects

          0  Goldstein (1952) reported that a  1% solution of endothall applied to
              the unbroken skin of rabbits produced no effects.  The same solution

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Endothall                                                        August, 1987

                                     -5-


        applied to scarified skin resulted in mild skin lesions.  Ten to
        twenty percent solutions or applications of the pure, powdered
        material to intact or scarified skin resulted in more severe damage,
        including necrosis,  and the deaths of some treated animals.

     0  Topical exposure of  six rabbits to 200 mg endothall technical/kg
        resulted in the death of all rabbits within 24 hours (Pharmacology
        Research, Inc.,  1975a).

     0  Technical endothall (0.1 g equivalent to 80 mg endothall ion) produced
        severe eye irritation in three rabbits when directly applied to the
        conjunctiva.   Effects included corneal opacity, conjunctival irritation
        and iridic congestion.  Furthermore, technical endothall apparently
        produced systemic effects by this route of absorption,  since several
        animals died within 24 hours as a result of this exposure.  Eyes were
        rinsed with water 20 to 30 seconds after treatment in three rabbits;
        conjunctival irritation and iridic congestion reversed in 4 days in
        two rabbits but persisted along with corneal opacity in one rabbit
        for 7 days (Pharmacology Research, Inc., 1975b).

   Long-term Exposure

     0  Beagle dogs (four/sex/group) fed diets containing 0, 100, 300 or
        800 ppm disodium endothall  (equivalent to 0, 2, 6 or 16 mg endothall
        ion/kg/day for 24 months showed no gross signs of toxicity (Keller,
         1965).  Values for hematology, urinalysis, weight gain and food
        consumption were within normal limits and comparable to those for
        control animals.  Increased stomach and small intestine weights were
        observed in the intermediate and high-dose groups.  However, microscopic
         examination of essentially  all tissues in the high-dose group revealed
        no pathological changes that could be attributed to endothall ingestion.
        A No-Observed-Adverse-Effect-Level (NOAEL) of 2 mg endothall ion/kg/day
        is identified from this study.

     0  Brieger  (1953b) reported no toxic effects in female rats given dietary
         levels as high as 2,500 ppm disodium endothall  (about 100 mg endothall
         ion/kg/day, assuming  food intake of 20 g/day and mean body weight of
         0.4 kg)  for 2 years.

   Reproductive  Effects

     0  A three-generation study in rats was reported by Scientific Associates
         (1965).  Groups of male and female rats were fed diets  containing 0,
         100,  300 or 2,500 ppm  disodium endothall  (equivalent to 0, 4, 12 or
         100 mg endothall ion/kg/day) until they were 100 days old and were
         then  mated.  Three successive generations of offspring  were maintained
         on the test diet for  100 days and then bred  to  produce  the next test
         generation.  Pups in  the 4-mg/kg/day dose group were normal, pups in
         the 12-mg/kg/day group had  decreased body weights at 21 days of age
         and pups in the 100 mg/kg/day group did not  survive more  than 1 week.
         A NOAEL  for reproductive effects of 4 mg  endothall ion/kg/day was
         identified from this  study.

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   Endothall                                                         August,  1987

                                        -6-


      Developmental Effects

        •  A  short-term teratology  study in  rats  by  Science Applications,  Inc.
           (1982)  indicated no observable signs of developmental  toxicity  at
           dose  levels that were fatal  to the  dams.  This study suggests that
           the dams are. more susceptible to  endothall than are the  embryos or
           fetuses.  Groups of 25 or  26 female rats  were mated and  then orally
           dosed with 0, 10, 20 or  30 mg/kg/day of aqueous endothall technical
           (0, 8,  16 or 24 mg endothall ion/kg/day)  on days 6 to  19 of  gestation.
           Two dams died from the 20-mg/kg/day dose, and 10 dams  died from the
           30-mg/kg/day dose.  No clinical signs  were noted prior to death,  and
           no lesions were observed at  necropsy.  The researchers concluded  that
           endothall technical was  not  embryotoxic or teratogenic at maternal
           doses of 30 mg/kg/day or below.  A  NOAEL  of 10 mg endothall
           technical/kg/day based on  maternal  effects was identified.

      Mutagenicity

        0  Mutagenicity results from  short-term in_ vitro tests are  mixed,  with
           various forms of endothall reported as test agents.  Mutagenicity
           studies utilizing Salmonella with and  without metabolic  activation
           resulted in negative findings for endothall technical  (Andersen
           et al., 1972; Microbiological Associates, 1980a).  Mutagenic activity
           was not found in BALB/3T3  Clone A31 mouse cells exposed  to endothall
           technical (Microbiological Associates, 1982b).

        0  For  the following studies, Wilson et al.  (1956) used  "commercial
           Endothall" with no further description, whereas the remaining investi-
           gators  used Aquathol K,  a  commercial formulation containing  dipotassium
           endothall at a level of  28.6% acid  equivalent.  In Drosophila melano-
           gaster, mutagenic results  were mixed,  with Wilson et al. (1956) and
           Sandier and Hamilton-Byrd  (1981)  reporting positive and  negative
           results, respectively.   Sandier and Hamilton-Byrd (1981) reported
           negative results in a mutagenicity  assay  with the mold Neurospora
           crassa. A sister chromatid  exchange study in human lymphocytes was
           negative (Vigfusson, 1981).   Transformation was induced  in a BALB/c
           3T3  test for malignant transformation  (Litton Bionetics, Inc.,  1981).

      Carcinogenicity

        0  No statistically significant numbers or types of tumors  were observed
           in rats fed as much as 100 mg endothall ion/kg/day for 2 years
           (Brieger, 1953b).
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
   *Because the test material  in  the various toxicity studies  was  salt or acid
    forms of endothall,  the  HAs described below are expressed  in terms of
    endothall ion.

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Endothall                                                        August, 1987

                                     -7-
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)
where:

        NOAEL or LOAEL = No- or Lowest-Observed-Adverse-Effect-Level
                         in mg/kg bw/day.

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

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

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

One-day Health Advisory

     No studies were located in available literature that were suitable for
calculation of the One-day HA.  The single-dose studies measured mortality as
the toxicological end point and are not suitable for use in calculating an HA.
The value of 0.8 mg/L calculated as the Ten-day HA can be used as a conservative
estimate of the One-day HA.

Ten-day Health Advisory

     The teratology study by Science Applications,  Inc. (1982) has been
selected as the basis for the Ten-day HA.  It is the only study that defined
a short-term NOAEL (8 mg endothall ion/kg/day, based on maternal toxicity).

     The Ten-day HA for a 10-kg child is calculated as follows:

           Ten-day HA *  (a ag/kg/day) (10 kg) = 0.8   /L (800   /L)
                           (100)  (1 L/day)
where:
        8 mg/kg/day = NOAEL based on the absence of fetal and maternal
                      effects in rats exposed to endothall acid orally for
                      13 days.

              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.

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Endothall                                                        August, 1987

                                     -8-


Longer-term Health Advisory

     There is concluded to be insufficient data for calculation of a Longer-
term HA.  Therefore, the DWEL adjusted for a 10-kg child (0.2 mg/L) is propose^
as a conservative estimate for a Longer-term HA.

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 litely 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 classifed 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 riste associated with lifetime exposure to this chemical.

     The 2-year feeding study in dogs by Keller (1965), which identified a
NOAEL of 2 mg endothall ion/kg/day, has been selected to serve as the basis
for the Lifetime HA for endothall.  The study by Scientific Associates (1965)
was of shorter duration (100 days/generation) and did not as completely
define a NOAEL (except for 4 mg endothall ion/kg/day for reproductive effects);
however, the NOAEL in this study approximates that in the Keller  (1965)
study.  The 2-year study in rats by Brieger  (1953b) showed no adverse effects
from doses up to 100 mg endothall ion/kg/day, but no information was provided
on the parameters tested and the levels at which effects did occur.

     Using the NOAEL of 2 mg/kg/day, the Lifetime HA for endothall is calculated
as follows:

Step 1:  Determination of the Reference Dose (RfD)

                     RfD = (2 mg/kg/day) = 0<02

where:

        2 mg/Jq/day = NOAEL, based on absence of increased organ weight and
                      organ-body weight ratios in the stomach and small
                      intestine in dogs exposed to endothall in the diet
                      for 2 years.

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    Endothall                                                        August, 1987
                          f

                                         -9-


                    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 = (0.02 mg/kg/day)  (70 kg) . 0>7 mg/L (700 u /L)
                              (2 L/day)

    where:

            0.02 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 *  (0.7 mg/L) (20%) =0.14 mg/L (140 ug/L)

    where:

            0.7 mg/L » DWEL.

                 20% » assumed percentage of daily exposure contributed by
                       ingestion of drinking water.

    Evaluation of Carcinogenic Potential

         0   Available toxicity data do not show endothall as carcinogenic.

         0   Endothall can be placed in Group D (inadequate evidence in humans
            and animals)  by the EPA's guidelines for carcinogenic risk assessment
            (U.S. EPA, 1986).

         8   The International  Agency  for Research on Cancer has not evaluated the
            carcinogenic potential of endothall (WHO, 1982).


VI.  OTHER CRITERIA,  GUIDANCE AND STANDARDS

         8   An interim tolerance of 200  ug/L has been published for residues of
            endothall, used to control aquatic plants, in potable water (CFR,
            1979).

         8   Residue  tolerances for endothall published by the  U.S.  EPA (CFR,
            1977) include 0.1  ppm in  or  on cottonseed, 0.1  ppm in or on potatoes,
            0.05 ppm in or on  rice grain and 0.05 ppm in or on rice straw.

         0   A tolerance is a derived  value based on residue levels,  toxicity
            data, food consumption levels,  hazard evaluation and scientific
            judgment;  it is the legal maximum  concentration of a pesticide
            in or on a raw agricultural  commodity or other  human or animal food
            (Paynter et al., undated).

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      Endothall                                                        August, 1987
                   f
                                           -10-


           0  The ADI set by the U.S.  EPA Office of Pesticide Programs is 0.02
              rag/kg/day based on the 2 mg/kg/day NOAEL in the 2-year dog study by
              Keller (1965)  and a 100-fold uncertainty factor.


 VII. ANALYTICAL METHODS

           0  No information was found in the available literature on the analytical
              methods used to detect endothall in drinking water.

VIII. TREATMENT TECHNOLOGIES

           8  No information was found in the available literature on treatment
              technologies capable of effectively removing endothall from contaminated
              water.

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    Endothall                                                        August, 1987

                                         -11-


IX. REFERENCES

    Allender, W.J.   1983.   Suicidal poisoning by endothall.   J. Anal. Toxicol.
         7:79-82.

    Andersen, K.J.,  E.G.-Leighty  and M.T.  Takahashi.   1972.  ^Evaluation of herbi-
         cides for  possible mutagenic properties.  J.  Agr.  Food Chem.  20:649-654.

    Brieger,  H.*  1953a.   Preliminary studies on the toxicity of endothall
         (disodium).   EPA  Pesticide Petition No. 6G0503, redesignated No. 7F0570,
         1966.  Accession  No.  246012.

    Brieger,  H.*  1953b.   Endothall, long  term oral toxicity test—rats.  EPA
         Pesticide  Petition No.  6G0503,  redesignated No. 7F0570, 1966.  Accession
         No.  246012.

    Carlson,  R., R.  Whitaker and  A. Landskov.  1978.   Endothall.  Chapter 31.
         In  G.  Zweig  and  J. Sherma, eds.   Analytical  methods for pesticides and
         plant growth.   New York:   Academic Press,  pp.  327-340.

    CFR.  1977.  Code  of Federal  Regulations.  40 CFR  180.293.

    CFR.  1979.  Code  of Federal  Regulations.  21 CFR  193.180.   April 1, 1979.

    Goldstein, F.   1952.   Cutaneous and  intravenous toxicity of endothall
         (disodium-3-endohexahydrophthalic acid).  Pharmacol.  Exp.  Ther.  11:349.

    Keller, J.*  1965.   Two year  chronic feeding study of disodium endothall to
         beagle dogs.   Scientific Associates report.   EPA Pesticide Petition
         6G0503, redesignated  No.  7F0570,  June 1966.   Accession No. 24601.

    Litton Bionetics,  Inc.   1981.   Evaluation of Aquathol K  in  the in vitro
         transformation of  BALB/3T3 cells  with and  without metabolic activation
         assay.  Project No. 20992.  Report to Municipality  of  Metropolitan
         Seattle, Seattle,  WA, by Litton Bionetics, Inc., Rockville, MD.

    Microbiological  Associates.*   1980a.  Activity  of  T1604  in  the Salmonella/
         microsomal  assay  for  bacterial  mutagenicity.   Unpublished final report
         for  Pennwalt  Corp.  by Microbiological Associates,  Bethesda, MD.

    Microbiological  Associates.*   1980b.  Activity  of  T1604  in  the in vitro
         mammalian  cell point  mutation assay in the absence  of  exogenous metabolic
         activation.   Unpublished final  report for  Pennwalt  Corp. by Microbiological
         Associates, Bethesda, MD.

    Paynter,  O.E.,  J.G.  Cummings  and M.H.  Rogoff.  Undated.   United States
         Pesticide  Tolerance System,  U.S.  EPA, Office  of Pesticide Programs,
         Washington, DC.   Unpublished draft report.

    Pharmacology Research,  Inc.*   1975a.   U.S.  EPA  Pesticide Resubmission File
         4581-EIE.   Summary  data  on acute  oral toxicity and  dermal  irritation in
         rabbits (Endothall).  Accession No.  244125.

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Endothall                                                        August, 1987

                                     -12-
Pharmacology Research,  Inc.*  1975b.   U.S. EPA Pesticide Resubmission File.
     Summary data,  primary eye irritation in the rabbit and inhalation toxicity
     in several species (Endothall).   Accession No. 246012.

Sandier, L., and E.L.  Hamilton-Byrd.   1981.  The induction of sex-linked
     recessive ethal mutations in Drosophila melanogaster by Aquathol K, as
     measured by the Muller-5 test.   Report to Municipality of Metropolitan
     Seattle, Seattle,  WA.

Scientific Associates.*  1965.  Three generation rat reproductive study,
     disodium endothall.   EPA Pesticide Petition No. 6G0503, redesignated
     7F0570, 1966.   EPA Accession No. 114667.

Science Applications,  Inc.*  1982.  A dose range-finding teratology study of
     endothall technical and disodium endothall in albino rats.  Resubmission
     of Pesticide Application for Aquathol K Aquatic Herbicide (EPA Registra-
     tion No. 4581-204) and Hydrothal 191 Aquatic Algicide and Herbicide
     (EPA Registration No. 4581-174).  EPA Accession No. 071249.

Simsiman, G.V., T.C. Daniel and G. Chesters.  1976.  Diquat and endothall:
     Their fates in the environment.   Res. Rev.  62:131-174.

Soo, A., I. Tinsley and S.C. Fang.  1967.  Metabolism of 14C-endothall in
     rats.  J. Agric.  Food Chem.  15:1018-1021.

Srensek, S.E., and G.  Woodard.  1951.  Pharmacological actions of "endothall"
     (disodium-3,6-endoxo-hexahydrophthalic acid).  Fed. Proc.  10:337.
     (Abstract)

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