820K88008
                                                                    August, 1987
                                 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, 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.
   Iacause each  model is  based on differing assumptions, the estimates that are
   derived can differ by  several orders  of magnitude.

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                                                                      August,  1987

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II. GENERAL INFORMATION AND PROPERTIES
    CAS No.   25057-89-0
    Structural Formula
           3-(1-Methy1ethyl)-1H-2,1,3-benzothiadiazin-4(3H)-one,2,2-dioxide

    Synonyms

         0  Basagran;  Bendioxide;  Bentazone  (Worthing,  1983).

    Uses

         0  Selective postemergent herbicide  used  to  control broadleaf  weeds  in
            soybeans,  rice,  corn,  peanuts, dry beans, dry peas,  snap beans  for
            seed, green lima beans and mint  (Meister, 1986).

    Properties   (Worthing,  1983)

            Chemical  Formula               €•) gHi 2N2°3S
            Molecular Weight               240.3
            Physical  State                  Colorless crystalline powder
            Boiling Point                  —
            Melting Point                   137  to 139°C
            Density                        —
            Vapor Pressure
            Water Solubility                500  mg/L
            Log Octanol/Water Partition     —
              Coefficient
            Taste Threshold                 ~
            Odor Threshold
            Conversion Factor

    Occurrence

         0  Bentazon  was not found in sampling performed at two  water supply
            stations  in the  STORET database  (STORET,  1987).  No  information
            on the  occurrence of bentazon was found in  the  available literature.

    Environmental Fate

         0  Bentazon,  at 1 ppm, was  stable to hydrolysis for up  to  122  days in
            unbuffered  water (initial pH 5, 7, and 9) at 22°C  (Drescher,  1972c).

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Bentazon           ?                                               August, T987

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        The bentazon degradate,  2-amino-N-isopropyl benzamide (AIBA) at
        1 ppm,  was stable to hydrolysis in unbuffered, distilled water at pH 5,
        7,  and  9,  during 28 days'  incubation in the dark at 22°C (Drescher,
        1973b).

     0  14c-Bentazon at 2 to 10  ppm,  degraded with a half-life of less than
        2 to 14 weeks in a sandy clay loam, loam, and three loamy sand soils
        (Drescher  and Otto, 1973a;  Drescher and Otto, 1973b).  The soils were
        incubated  at 14 to 72% of field capacity and 23°C.  The bentazon
        degradation rate was not affected by soil moisture content but was
        decreased  by lowering the temperatures to 8 to 10°C.  At pH 6.4, the
        degradation rate in a loamy sand soil was 2.5 times longer than at
        pH 4.6  and 5.5.  The bentazon degradate, AIBA, was identified at less
        than 0.1 ppm.  AIBA degraded  in loamy sand soil with a half-life of
        1 to 10 days (43% of field capacity).  14c-Bentazon at 1.7 ppm did
        not degrade appreciably  in a  loamy sand soil during 8 weeks of incubation;
        AIBA was detected at a maximum concentration of 0.008 ppm.

     0  Bentazon did not adsorb  to Drummer silty clay loam, adjusted to pH 5
        and 7,  and 11 other soils tested at pH 5 (Abernathy and Wax,
        1973).   In the same study,  using soil TLC, (14c)bentazon was very
        mobile  in  12 soils, ranging in texture from sand to silty clay loam,
        with an Rf value of 1.0.

     0  Bentazon was very mobile in a variety of soils, ranging in texture
        from loamy sand to silty clay loam and muck, based on soil column
        tests (Drescher and Otto,  1972; Abernathy and Wax, 1973; Drescher,
        1973a;  Drescher, 1972a).  Approximately 73 to 103% of the bentazon
        applied to the columns was recovered in the leachate.

     0  AIBA (100  ug applied to  loamy sand soil) was very mobile (Drescher,
        1972b). After leaching  a 12-inch soil column with 500 ml (10 inches)
        of distilled water, 86.3% of  the applied material was found in the
        leachate.

     0  Bentazon has the potential  to contaminate surface waters as a result
        of its  mobility in runoff water and application to rice fields
        (Devine, 1972; Wuerzer,  1972).

     0  In the  field, bentazon at 0.75 to 10 Ib ai/A dissipated with a half-
        life of less than or equal  to 1 month in the upper 6 inches of soil,
        ranging in texture from  sand  to clay (Daniels et al., 1976; Devine
        and Hanes, 1973; Stoner  and Hanes, 1974b; Stoner and Hanes, 1974a;
        BASF Wyandotte Corporation, 1974; Devine and Tietjens, 1973; Devine
        et al., 1973).  In the majority of soils (6 of 9), bentazon had a
        half-life  of less than 7 days.  AIBA was detected at less than or
        equal to 0.09 ppm.  Collectively, the available data indicated that
        geographic region (NC, TX,  MS, AL, MN,  or ID) and crops treated
        (peanuts,  soybeans, corn or fallow soil) had little or no effect on
        the dissipation rate of  bentazon in soil.

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     Bentazon                                                         August,  1987

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III.  PHARMACOKINETICS

     Absorption

          0  Male  and  female  rats  (200 to  250 g) given 0.8 mg 14c-bentazon in 1  mL
            of  50% ethanol by stomach tube excreted 91% of  the administered  dose
            in  the urine within 24 hours.  This suggests that bentazon  is almost
            completely  absorbed when ingested  (Chasseaud et al.,  1972).

     Distribution

          0  Whole-body  autoradiography of rats indicated high levels of  radio-
            activity  in the  stomach, liver, heart  and kidneys after  1 hour of
            dosing with 14c-bentazon.  Radioactivity was not observed in the brain
            or  spinal cord  (Chasseaud et  al.,  1972).

     Metabolism

          0  Bentazon  is poorly metabolized.  Two unidentified metabolites
            were  detected  (Chasseaud et al., 1972).
     Excretion
             Rats given radiolabeled  bentazon  excreted  91%  of  the administered dose
             in the urine as  parent compound.   Feces  contained 0.9%  of  the administer^
             dose (Chasseaud  et al.,  1972).
 IV. HEALTH EFFECTS
     Humans
             No information on the health effects  of  bentazon in humans was found
             in the available literature.
     Animals
        Short-term Exposure

          0  The oral LD5Q of bentazon in the rat was  reported  to be 2,063 mg/kg
             (Meister, 1986).

          e  LDso values for bentazon in the rat, dog, cat and  rabbit are reported
             to be 1,100,  900, 500 and 750 mg/kg, respectively  (RTECS,  1985).

          •  Acute, subchronic and chronic oncogenicity studies on bentazon have
             been invalidated because of data gaps and deficiencies.  However,  the
             RfD Workgroup (U.S.  EPA 1986a)  calculated a Reference Dose (RfD) for
             bentazon from a 13-week study in dogs.   This study is described in
             detail in Section V.  Quantification of Toxicological Effects.  Note
             that the calculated  RfD value has a low confidence level.

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   Bentazon                                                        August, 1987
                                                        )
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      Dermal/Ocular Effects

        0  No valid information on the dermal/ocular effects of bentazon was
           found in the available literature.

      Long-term Exposure

        e  As indicated under Short-term Exposure,  long-term studies, including
           reproductive effects and carcinogenicity studies, have been invalidated,

      Reproductive Effects

        8  No valid information on the reproductive effects of bentazon was
           found in the available literature.

      Developmental Effects

        8  No valid information on the developmental effects of bentazon was
           found in the available literature.

      Mutagenicity

        8  No valid information on the mutagenic effects of bentazon was found
           in the available literature.

      Carcinogenici ty

        8  No valid information on the carcinogenic effects of bentazon was
           found in the available literature.


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:

                 HA = JNOAEL or LOAEL) x (BW)  . 	   /L {	   /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).

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Bentazon                                                          August, 1987
                                                     «
                                     -6-


One-day Health Advisory

     No data were found in the available literature that were suitable for
determination of One-day HA values.   It is, therefore,  recommended that the
Longer-term HA value for a 10-kg child (0.25 mg/L,  calculated below) be used
at this time as a conservative estimate of the One-day HA.

Ten-day Health Advisory

     No data were found in the available literature that were suitable for
determination of Ten-day HA values.   It is, therefore,  recommended that the
Longer-term HA value for a 10-kg child (0.25 mg/L,  calculated below) be used
at this time as a conservative estimate of the Ten-day HA.

Longer-term Health Advisory

     A 13-week study in beagle dogs  has been selected for the calculation of
a Longer-term HA (Leuschner et al.,  1970).  Beagle dogs (three  dogs/sex/dose)
were gven 0 (control), 100, 300, 1,000 and 3,000 ppm (0, 2.5, 7.5, 25 and
75 mg/kg/day; Lehman, 1959) of bentazon for 13 weeks.  At a dose level of
3,000 ppm, overt signs of toxicity,  including weight loss and ill health, were
observed; 1/3 males and 2/3 females  died.  At 3,000 ppm, all males showed signs
of prostatitis.  Similar signs were observed in one male each at the 300- and
1,000-ppm levels.  This study suggests a NOAEL of 100 ppm (2.5 mg/kg/day).

     Utilizing this NOAEL, a Longer-term HA for a 10-kg child is calculated
as follows:

       Longer-term HA « (2.5 ing/kg/day)  (10 kg) m 0.25 mg/L  (250 ug/L)
                            (100) (1 L/day)

where:

        2.5 mg/kg/day » NOAEL, based on  absence of prostatic effects in dogs.

                 10 kg » assumed body weight of a child.

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

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

     The  Longer-term HA for the 70-kg adult is calculated as follows:

       Longer-term HA «  (2.5 mg/kg/day)  (70 kg) . 0>875   /L (875   /L)
                            (100) (2 L/day)

where:

         2.5 mg/kg/day » NOAEL, based on  absence of prostatic effects in dogs.

                 70 kg » assumed body weight of an adult.

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Bentazon
August, 1987
                                     -7-
                  100 - uncertainty factor, chosen in accordance with NAS/OEW
                        guidelines for use with a NOAEL from an animal studyc

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

Lifetime Health Advisory

     Tha 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,  1986b), then caution should be exercised in
assessing the risks associated with  lifetime exposure to this chemical.

     Lifetime studies were not available to calculate a Lifetime HA.  However,
with the addition of another safety  factor of 10 for  studies of less-than-
lifetime duration, the Lifetime HA may be calculated  from the 13-week feeding
study in dogs (Leuschner et al., 1970).

     Using the NOAEL of 2.5 mg/kg/day, the Lifetime HA for bentazon is
calculated as follows:

Step 1:  Determination of a the Reference Dose (RfD)

                   RfD = (2.5 mg/kg/day) = 0.0025 mg/kg/day
                             (1,000)                   y   y
where:
        2.5 mg/kg/day = NOAEL,  based  on the absence of prostatic effects in
                        dogs.

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

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     Bentazon                                                          August,

                                          -8-


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

              DWEL  »  (0.0025 mg/kg/day)  (70  kg)  ,  0.0875  mg/L (87.5 ug/L)
                             (2 L/day)

     where:

             0.0025 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 -  (0.0875 mg/L)  (20%)  *  0.0175  mg/L (17.5 ug/L)

     where:

             0.0875 mg/L = DWEL.

                     20% * assumed  relative  source contribution from water.


     Evaluation of  Carcinogenic Potential

          0   No valid  data are  available to  make a determination  of the carcino-
             genic  potential of bentazon.

          e   Applying  the criteria  described in  EPA's guidelines  for assessment
             of carcinogenic risk (U.S.  EPA, 1986b), bentazon may be classified
             in Group  D: not Classified.  This  category  is  for agents with  inadequate
             animal evidence of carcinogenicity.


 VI.  OTHER CRITERIA, GUIDANCE AND STANDARDS

          c   In response to  a bentazon-tolerance review petition,  EPA's Office of
             Pesticide Programs has concluded  that "a tolerance cannot be  supported
             at this time."


VII.  ANALYTICAL METHODS

          *   Analysis  of bentazon is  by  a  gas  chromatographic (GC) method  applicable
             to the determination of  bentazon  in water  samples (U.S. EPA,  1985).
             In this method, an aliquot  of sample  is acidified and extracted with
             ethyl  acetate.   The extract is  dried, concentrated to 1 to 2  mL, and
             methylated  with diazomethane.  The  methylated extracts are analyzed
             by gas chromatography  with  flame  photometric detection.  The  method
             detection limit for bentazon has  not  been  determined.

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      Bentazon                                                          August,  1987

                                           -9-


VIII. TREATMENT TECHNOLOGIES

           0  There is no information available regarding  treatment technologies
              used  to  remove  bentazon from  contaminated  water.

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    Bentazon                                                          August, 1987

                                         -10-


IX. REFERENCES

    Abernathy,  J.  R.  and L.  M.  Wax.   1973.   Bentazon nobility and adsorption in
         twelve Illinois soils.   Weed Science.   21(3):224-226.

    BASF Wyandotte Corporation.   1974.   Analytical residue reports (soil and
         water):   bentazon.   Unpublished study.

    Chasseaud,  L.F.,  O.R.  Hawkins,  B.D.  Cameron,  B.J. Fry and V.H. Saggers.  1972,
         The metabolic fate  of  bentazon.  Xenobiotica.  2(3):269-276.

    Daniels, J.,  J.  Gricher  and  T.  Boswell.   1976.  Determination of bentazon
         (BAS 351-H)  residues in sand soil samples from Yoakuro, Texas:  Report
         No. IRDC-3;  BWC Project No.  I-2-G-73.   Unpublished study prepared by
         International Research  and Development  Corporation, submitted by BASF
         Wyandotte Corporation,  Wyandotte,  MI.

    Devine,  J.  M.   1972.  Determination  of BAS 351-H (3-isopropyl-lH-2,l,3-benzo-
         thiadiazin-4(3H)-one-2,2-dioxide)  residues in soil and runoff water.
         Report No.  133.

    Devine,  J.  M.  and R. E.  Hanes.   1973.  Determination of residues of BAS
         351-H(3-isopropyl-lH-2,l,3-benzothiadiazin-4(3H)-one-2,2-dioxide) and
         its benzamide metabolite,  AIBA  (2-amino-N-isopropyl benzamide), in
         Sharkey silty clay  soil from Greenville,  Mississippi:  Field Experiment
         No.  72-99.   Unpublished study  prepared by State University of New
         York—Oswego, Lake  Ontario Environmental Laboratory and United States
         Testing Company, inc.,  submitted by BASF Wyandotte Corporation,
         Parsippany,  NJ.

    Devine,  J.  M. and F. Tietjens.   1973.  Determination of BAS 351-H (3-isopropyl-
         lH-2,l,3-benzothiadiazin-4(3H)-one-2,2-dioxide) residues in Commerce
         silt loam soil from Greenville, Mississippi:  Field Experiment No. 72-76.
         Unpublished study prepared by State Univeristy of New York—Oswego, Lake
         Ontario Environmental Laboratory and United States Testing Company,
         Inc.,  submitted by  BASF Wyandotte Corporation, Parsippany, NJ.

    Devine,  J.  M., C. Carter, L. W. Hendrick et al.  1973.  Determination of
         residues of BAS 351-H (3-isopropyl-lH-2,l,3-benzothiadiazin-4(3H)-one-
         2,2-dioxide) and its benzamide metabolite, AIBA (2-amino-N-isoopropyl
         benzamide), in Webster Glencoe silty clay loam soil from Prior Lake,
         Minnesota:  Field Experiment No. III-B-6-72.  Unpublished study prepared
         by State University of New York~Oswego, Lake Ontario Environmental
         Laboratory and others,  submitted by BASF Wyandotte Corporation,
         Parsippany,  NJ.

    Drescher, N.  1972a.  A  comparison between the leaching of bentazon and 2,4-D
         through a soil in a model experiment:   Laboratory Report No. 679.

    Drescher, N.  1972b.  Leaching of 2-aminc—N-isopropyl benzamide (AIBA) from
         the soil.  Laboratory Report No. 682.

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Bentazon                                    '                    August,  1987

                                     -11-
Drescher, N.  1972c.  The effect of pH on the rate of hydrolysis of bentazon
     (HAS 351-H) in water:  Laboratory Report No. 1107.  Translation;
     unpublished study prepared by Badische Anilin- and Soda-Fabrik, AG,
     submitted by BASF Wyandotte Corporation, Parsippany, NJ.

Drescher, N.  1973a.  Leaching of bentazon in a muck soil.  Laboratory  Report
     No. 1138.

Drescher, N.  1973b.  The influence of pH on the hydrolysis of the bentazon
     metabolite AIBA (2-amino-N-isopropyl benzamide) in water.  Laboratory
     Report No. 1136.

Drescher, N. and S. Otto.  1972.  Penetration and leaching of bentazon  in
     soil:  Laboratory Report No. 1099.  Translation; unpublished study
     prepared by BASF, AG, submitted by BASF Wyandotte Corporation,
     Parsippany, NJ.

Drescher, N. and S. Otto.  1973a.  Degradation of bentazon (BAS 351-H)  in
     soil.  Report No. 1140.

Drescher, N., and S. Otto.  1973b.  Degradation of bentazon (BAS 351-H) in
     soil.  Report No. 1149.

Lehman, A.J.  1959.  Appraisal of the safety of chemicals in foods, drugs and
     cosmetics.  Assoc. Food Drug Off. U.S.

Leuschner, F., A. Leuschner, W. Schwerdtfeger and H. Otto.  1970.  13-Week
     toxicity study of 3-isopropyl-1H-2,1,3-benzothiadiazin-4(3H)-one-2,2-
     dioxide to beagles when administered with the food.  Unpublished report
     prepared by Laboratory of Pharmacology and Toxicology, W. Germany.
     September 28.

Meister, R., ed.  1986.  Farm chemicals handbook.  Willoughby, OH:  Meister
     Publishing Co.

RTECS.  1985.  Registry of Toxic Effects of Chemical Substances.  National
     Institute for Occupational Safety and Health.  National Library of
     Medicine Online File.

Stoner, J.H., and R.E. Hanes.  1974a.  Determination of residues of bentazon
     and AIBA (2-amino-N-isopropyl benzamide) in Commerce silt loam soil from
     Greenville, MS:  Field Experiment No. 73-41.  Unpublished study prepared
     in cooperation with Stoner Laboratories, Inc., and United States Testing
     Company, Inc., submitted by BASF Wyandotte Corporation,  Parsippany, NJ.

Stoner, J. H., and R. E. Hanes.  I974b.  Determination of residues of bentazon
     (BAS 351-H) and AIBA i'n Commerce silt loam soil from Greenville, MS:
     Field Experiment No. 73-43.  Unpublished study prepared in cooperation
     with Stoner Laboratories, Inc.  and United States Testing Company,  Inc.,
     submitted by BASF Wyandotte Corporation, Parsippany, NJ.

STORET.  1987.

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Bentazon                                                        August, 1987

                                     -12-
U.S. EPA.  1985.  U.S. Environmental Protection Agency.  U.S. EPA Method 107
     • Revision A,  Bentazon.  Fed. Reg.  SO:40701.  October 4, 1985.

U.S. EPA.  1986a.  U.S. Environmental Protection Agency.  RfD Work Group.
     Worksheet dated April 7.

U.S. EPA.  1986b.  U.S. Environmental Protection Agency.  Guidelines for
     carcinogen risk assessment.  Fed. Reg.  51 {1 85):33992-34003.
     September 24.

Worthing, C.R., ed.  1983.  The pesticide manual.  Great Britain:  The Lavenham
     Press, Ltd., p. 39.

Wuerzer, B.  1972.   Bentazon model box runoff study:  Runoff Report 73-6.
     Unpublished study prepared in cooperation with United States Testing
     Company, submitted by BASF Wyandotte Corporation, Parsippany, NJ.

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