August,  1987

           820K88124
                                     BUTYLATE
                                 Health Advisory
                             Office of Drinking Water
                       U.S. Environmental  Protection Agency
DRAFT
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.
   Because each model is based on differing assumptions, the estimates that are
   derived can differ by several orders of  magnitude.

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    Butylate
                          August, 1987
                                        -2-
II. GENERAL INFORMATION AND PROPERTIES
    CAS No.   2008-41-5
    Structural  Formula
                               H5c2-s-c-N;
                                           \.
                                                 •CH2CH(CH3)2

                Carbamothioic acid, bis(2-methylpropyl)-, S-ethyl ester
    Synonyms
            S-ethyl di-isobutylthiocarbamate; S-ethyl bis(2-methylpropyl)
            carbamothioate; ethyl N,N-di-isobutyl thiocarbamate; S-ethyl-di-isobutyl
            thiocarbamate; ethyl-N,N-di-isobutyl thiolcarbamate; R-1910; Sutan*.
    Uses
       •  °  Selective preplant herbicide (Meister, 1983).

    Properties   (BCPC,  1977)
           Chemical Formula
           Molecular Weight
           Physical State  (25°C)
           Boiling Point
           Melting Point
           Density (25°C)
           Vapor  Pressure  (258C)
           Specific Gravity
           Water  Solubility  (20eC)
           Octanol/Water Partition
              Coefficient
           Taste  Threshold
           Odor Threshold
           Conversion  Factor
CnH23NOS
217.41
Clear liquid, aromatic odor
138°C

0.9417
1.3 x 10-3 nun Hg

45 rag/L
    Occurrence
            Butylate  has  been  found in 298 of 431 surface water samples
            analyzed  and  in none of 18 ground water samples  (STORET, 1987).
            Samples were  collected at 52 surface water locations and 18 ground
            water  locations, and butylate was found in 5 states.  The 85th
            percentile  of all  nonzero samples was 0.17 ug/L in surface water and
            0 ug/L in ground water sources.  The maximum concentration found was
            6 ug/L in surface  water and in 0 ug/L in ground water.

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     Butylate                                                        August,  1987

                                          -3-


     Environmental Fate

          0   Butylate  degrades  fairly  rapidly in  moist  soils  under aerobic condi-
             tions;  half-lives  were 3  to 10 weeks (Thomas  and Holt, 1979;  Shell
             Development Company,  1975;  Stauffer  Chemical  Company, 1975a).  Under
             anaerobic conditions, butylate degrades  with  a half-life of 13 weeks
             (Thomas et al.,  1978). Butylate sulfoxide is the major degradate,
             but s-ethyl-2,2-dimethyl-2-hydroxyethylisobutyl  thiocarbamate,
             diisobutylformamide,  diisobutylamine,  diisobutylthiocarbamate, and
             isobutylamine were also identified as  degradates (Thomas and  Holt,
             1979;  Thomas et  al.,  1978;  Shell Development  Company, 1975; Stauffer
             Chemical  Company,  1975a).

          0   Butylate  is slightly  mobile to highly  mobile  in  soils ranging in
             texture from silty clay loam to gravelly sand (Gray and Weierich,
             1966;  Lavy, 1974;  Thomas  and Holt, 1979; Weidner,  1974).

          0   Butylate  is fairly volatile; 45 to 50% of  14C- butylate applied  to
             moist (20% moisture)  Sorrento clay loam  was recovered as volatile
             radioactivity over 3  weeks  following treatment.   Volatile radioactivity
             was characterized  as  butylate (Thomas  and  Holt,  1979).

          0   In the field, butylate dissipated more readily in a soil in
             Florida than in  a  silty clay loam in California, probably leaching
             beyond the 6-inch  sampling  depth. The estimated half-lives in the
             upper 6 inches of  the sand  were 28 and 18  days when a 4 Ib/gal Mcap
             and a 6.7 Ib/gal EC formulation,  respectively, were applied at 8 Ib
             ai/A.   For the silty  clay loam,  estimated  half-lives were more than
             64 days for both the  Mcap and a 7 Ib/gal EC formulation applied  at
             8 Ib ai/A (active  ingredient/acre) (Stauffer  Chemical Company, 1975b;
             Stauffer  Chemical  Company,  1975c).

          0   Butylate  has a low bioaccumulation potential  in  bluegill sunfish.   A
             bioconcentration factor of  33 was found  in the edible portion of fish
             dosed with !4C-butylate at  0.01 or 1 ppm for  28  days.  The nonedible
             portion of fish  dosed at  0.01 and 1  ppm  exhibited bioconcentration
             factors of 174 and 122, respectively.  After  10  days of depuration,
             50 to 67% of the day-28 residues was lost  (Sleight, 1973).


III. PHARMACOKINETICS

     Absorption

          0   Data relating specifically  to the absorption  of  butylate were not
             located in the available  literature; however, some information was
             obtained  from a  metabolism  study by  Hubbell and  Casida (1977).  Doses
             of 12.3 or 156.0 mg/kg 14co-labeled  butylate  were administered by
             gavage  to male albino Sprague-Dawley rats  weighing 190 to 210 g.
             Within 48 hours, 27.3 and 31.5% of the administered radioactivity
             were recovered in  the urine, and 60.9  and  64.0%  were expired  as  14C02
             in the  low- and  high-dose groups, respectively.   These results indicate
             that butylate is appreciably absorbed  from the gastrointestinal  tract
             of rats.

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Butylate                                                        August, 1987
Distribution

     •  Hubbell and Casida (1977)  measured the tissue radioactivity 48 hours
        after the administration by gavage of 12.3 or 156.0 mg 14co-labeled
        butylate/kg to male Spr ague-Da wley rats.   At the low dose,  2.4% of
        the administered radioactivity was retained in the body,  with levels
        of radioactivity equivalent to 276 ppb in the blood, 524  ppb in the
        kidney, 710 ppb in the liver and a range of 182 to 545 ppb in other
        tissues (brain,  fat,  heart,  lung,  muscle, spleen and testes).  At the
        high dose, 2.2% of the radioactivity was retained in the  body with
        2,076 ppb in the blood, 5,320 ppb in the kidney, 7,720 ppb in the
        liver and 1,720 to 5,560 ppb in other tissues.

Metabolism

     0  Hubbell and Casida (1977)  followed the metabolism of butylate in male
        Spr ague-Da wley rats based upon identification of the 48-hour urinary
        metabolites of 14CO- labeled preparations of butylate (12.3 or 156
        n9/kg).  Degradation of administered butylate metabolites was also
        assessed.  Approximately 40% of the administered 14co-butylate was
        metabolized by ester cleavage and  4C02 liberation without going
        through the sulf oxide (the major metabolite) as an intermediate.  The
        metabolites from all compounds were essentially the same  qualitatively
        and quantitatively.  The metabolites for 14CO-butylate included, as
        percent of urinary radioactivity, 4.3% as the N,N-di-isobutyl mercapturil
        acid, 17.1% as the N-isobutylmercapturic acid, 0.8% as the mercaptoacetic"
        acid derivative, 11.7% as the glycine conjugate of the mercaptoacetic
        acid derivative and about 66% as at least 15 other metabolites.

     0  S-(1-14c)ethyl-Sutan®, orally administered at about 110 mg Sutan*/kg»
        was readily degraded and excreted by male and female Sprague-Dawley
        rats  (Thomas et al., 1980).  Cleavage of the S-ethyl moiety and the
        incorporation of the two-carbon fragment into intermediary metabolic
        pathways accounted for >70% of the total administered radiocarbon.
        Urinary excretion of 14C-hippuric acid, ethyl methyl sulf oxide and
        ethyl methyl sulfone was evident.
Excretion
        Hubbell and Casida (1977) administered 12.3 or 156 mg/kg of 1 Re-
        labeled butylate by gavage to adult male Sprague-Dawley rats.  Withi-r
        24 hours, 60.9 and 64.0% of the administered radioactivity were
        expired as CC>2, 27.3 and 31.5% were excreted in the urine and 3.3 and
        4.7% were excreted in the feces in the low- and high-dose groups,
        respectively.

        A study by Bova et al. (1978) indicates that biotransformation of
        S-(1-14c) ethyl-Sutan* in male and female Sprague-Dawley rats given
        oral doses of 83.5 to 133.5 mg Sutan*/kg involves rapid cleavage of
        the S-ethyl moiety.  Degradation of this fragment of the molecule
        results in the release of 14C02 as the major product of metabolism,
        accounting for 69% of the total administered dose.  This rapid pro-
        duction of 14C02 may account for the relatively high levels  (7.8%) of

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    Butylate                                               .         August,  1987
                found in the tissues  after  8  days.   Urine and feces accounted for
            13.9 and 3.2% of the  1 4c  dose,  respectively.

            Data obtained from  a  3-day balance  and  tissue residue study by Thomas
            et al.  (1979) show  that (1-14c-isobutyl)Sutan* is readily eliminated
            by male and  female  Sprague-Dawley rats  after  a single oral dose (about
            100 mg  Sutan*/kg).  More  than 99% of  the administered radiocarbon was
            recovered from the  animals within 72  hours after dosing.  Most of the
            dose (94%) was recovered  within 24  hours after treatment.   Less than
            0.5% of the  radiocarbon remained  in the tissues after 72 hours, and
            the Sutan® equivalents  in organ and tissue samples were all less than
            2 ppm.   Urine, feces  and  expired  14C02  accounted for 93.7, 4.0 and
            2.0% of the  dose, respectively.
IV. HEALTH EFFECTS
    Humans
            No information was  found  in  the  available literature on the health
            effects of butylate in humans.
    Animals
       Short-term Exposure

         0   The acute oral LD5g value  in  male and female rats given butylate
            technical (85.71% pure)  was 3.34  and 3.0 g/kg,  respectively (Raltech,
            1979).

       Dermal/Ocular Effects

         0   Skin irritation was observed  in rabbits topically exposed to 2 g
            butylate technical (85.71% pure)  for 24 hours (Raltech, 1979).

         0   Topical application of R-1910 6E  technical (97.5% pure) at doses of
            20 and 40 mg active ingredient (a.i.)/kg,  5 days per week for a total
            of 21 applications, was  without observed effect except for local skin
            irritation (Woodard Research  Corp.,  1967a).

         0   Application of butylate  technical (85.71% pure) to the eyes of rabbits
            resulted in irritation and corneal opacity.  No corneal opacity was in
            eyes washed after treatment  (Raltech, 1979).

       Long-term Exposure

         0   Dietary feeding of R-1910  technical  (97.5% pure) to male and female
            Charles River rats at dose levels of 32,  16 and 8 mg/kg/day for 13 weeks
            was without observable adverse effect.   The high dose (32 mg/kg/day)
            was identified as the No-Observed-Adverse-Effect-Level (NOAEL) for this
            study (Woodard Research  Corp., 1967b).

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Butylate                                                        August, 1987
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                                     -6-
     •  Dietary feeding of Sutan* Technical and Sutan* Analytical (purities
        not specified) to male Sprague-Oawley rats at dose levels as high as
        180 mg/kg/day for 15 weeks was without observable adverse effect
        (NOAEL) (Scholler, 1976).

     0  Results of a toxicity study in which male and female beagle dogs were
        fed R-1910 Technical (97.6% pure)  at dietary levels of 450, 900 and
        1,800 ppm (corresponding to doses  of 11,  23 and 45 mg/kg/day, assuming
        1  ppm equals 0.025 mg/kg/day from  Lehman, 1959) for 16 weeks were
        unremarkable (Woodard Research Corp., 1967c).  Hence,  45 mg/kg/day is
        identified as a NOAEL.

     0  Sutan* Technical (98% pure) was fed in the diet to male and female
        Sprague-Dawley rats at dose levels of 10, 30 and 90 mg/kg/day for 56
        weeks.  One group of rats was given 90 mg/kg/day for 15 weeks followed
        by 180 mg/kg/day for 41 weeks.  No systemic effects were found at
        10 mg/kg/day (NOAEL).  Testes/body weight ratios were significantly
        (p <0.05) lower in terminally sacrificed males given 30 and 90 mg/kg/day.
        Slight (8 to 15%) nonsignificant (p >0.05) mean body weight decreases
        were found in 30 and 90 nsg/kg males and 90 mg/kg females.  Liver to
        body weight increases and testicular lesions were found with the
        highest doses.  Blood clotting parameters were affected at all doses,
        with the effects at 10 mg/kg/day being significant (p <0.05) decreases
        in factor II times in males and activated partial thromboplastin
        times in females (Hazelton Laboratories, Inc., 1978).

     0  R-1910 Technical (purity not specified) was fed in the diet to male
        and female Sprague-Oawley CD rats at dose levels of 50, 100, 200 and
        400 mg/kg/day for 2 years.  Although significantly (p <0.05) elevated
        liver-to-body weight ratios occurred in terminally sacrificed males
        given 50 mg/kg/day, this effect was not observed in animals from this
        dose group sacrificed at 12 and 18 months.  Hence, 50 mg/kg/day was
        identified as a NOAEL.   In males and females, body weights were
        significantly (p <0.05) reduced, and liver to body weight ratios were
        significantly (p <0.05) increased with doses above 50 mg/kg/day.
        Neoplastic nodules and periportal hypertrophy in the liver were
        significantly (p <0.05) increased in males given 400 mg/kg/day
        (Biodynamics, 1982).

     0  Male and female Charles River CD-I mice were given Sutan* Technical
        (98% pure) in the diet at dose levels of 20, 80 and 120 mg/kg/day for
        2 years.  No effects were  found at 20 mg/kg/day (NOAEL).  Kidney and
        liver lesions were noted with higher doses (International Research
        and Development Corporation  [IRDC], 1979).

Reproductive Effects

     0  No information was found in  the available literature on the effects
        of butylate on reproduction.

Developmental Effects

     •  Sutan* Technical  (98.2% pure) was administered by gavage to pregnant
        rats at doses of 40, 400 and  1,000 mg/kg/day on days 6 through 20 of

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   Butylate                                                         August,  1987

                                       -7-
           gestation.   The  40 mg/kg/day dose  was  without  observable effect (NOAELK
           Higher doses decreased body weight gain in dams,  increased liver-to-
           body weights in  dams, decreased  fetal  body weights,  increased incidences
           of misaligned sternebrae  and delayed ossification,  and  increased
           early resorptions.  Sutan® was not teratogenic in this  study (Stauffer
           Chemical  Co.,  1983).

        0  Administration of R-1910  Technical (97.6%  pure) in  the  diet to pregnant
           Charles River mice at dose levels  of 4,  8  and  24  mg/kg/day either  on
           days 6 through 18 or  from day  6  until  natural  delivery  was without
           observable  effect (NOAEL) on dams  and  fetuses  (Woodard  Research
           Corp., 1967d).

      Mutagenicity

        0  Butylate  was not mutagenic in  Salmonella typhimurium strains TA1535,
           TA1537, TA1538 and TA100  with  or without the S-9  activating fraction
           (Eisenbeis  et al., 1981).

        0  in Drosophila melanogaster, butylate treatment increased the frequency
           of sex-linked recessive lethals  but had no effect on the frequency of
           dominant  lethals (Murnik, 1976).

      Carcinogenicity

        0  R-1910 Technical was  not  determined to be  carcinogenic  in the 2-year
           rat study by Biodynamics  (1982),  but a significant  (p <0.05) increase
           in neoplastic nodules in  liver in  high-dose males was evident.
           Neoplastic  nodules were found  in 2/69, 6/69, 1/69,  1/70 and 9/70
           males given 0 ppm  (control), 50  ppm, 100 ppm,  200 ppm and 400 ppm,
           respectively.  Hepatocellular  carcinomas were  found in  2/69, 3/69,
           4/69, 3/70  and 2/70 males given  0  ppm  (control),  50 ppm, 100 ppm,
           200 ppm and 400 ppm,  respectively.

        0  Sutan® Technical was  not  carcinogenic  in the 2-year mouse study by
           IRDC (1979).
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 = (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.

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Butylate                                                        August, 1987

                                     -8-
                    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 information was found in the available literature that was suitable
for determination of the One-day HA value for butylate.  It is,  therefore,
recommended that the Ten-day HA value (2.4  mg/L, calculated below) be used
at this time as a conservative estimate of  the One-day HA value.

Ten-day Health Advisory

     The teratology study in mice by Woodard Research Corporation (1967d)
has been selected to serve as the basis for determination of the Ten-day HA
value for butylate because it provides a short-term NOAEL (24 mg/kg/day for
13 days) for both maternal and fetal toxicity.  The teratology study in rats
by Stauffer (1983), which identified a NOAEL of 40 mg/kg/day (for 15 days)
for maternal and fetal effects, could also  be considered; however, because
doses higher than the 24 mg/kg/day NOAEL were not included in the Woodard
study (1967d), the effect levels in this study are uncertain.  Furthermore,
the agent was given in the diet in the Woodard study (1967d) and by gavage in
the Stauffer  (1983) study.  Therefore, dose-response comparisons in terms of
both effect and no-effect levels between the Woodard (1967d) and Stauffer
(1983) studies cannot be made.

     Using a NOAEL of 24 mg/kg/day, the Ten-day HA for a 10-kg child is
calculated as follows:

          Ten-Day HA = (24 mg/kg/day) (10 kg) = 2.4 mg/L (2,400 ug/L)
                           (1 L/day)  (100)
where:
        24 mg/kg/day = NOAEL based on the absence of fetal and maternal
                       effects in mice exposed to Sutan* Technical orally
                       for 13 days.

               10 kg = assumed body weight of a child.

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

                 100 * uncertainty factor, chosen in accordance with National
                       Academy of Sciences/Office of Drinking Water (NAS/ODW)
                       guidelines for use with a NOAEL from an animal study.

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 Butylate                                                        August, 1987

                                      -9-


 Longer-term Health Advisory

      The DWEL (2.45 mg/L)  is  recommended for use as  a  conservative estimate
 of the Longer-term HA  by  the  rationale given below.

      The 56-week  feeding  study  with  Sutan® Technical in  rats  by Hazelton
 Laboratories (1978) is a  possible  basis for a Longer-term HA.   However,
 effects observed  in this  study  were  not evident with higher doses in the
 2-year feeding study with R-1910 Technical in rats by  Biodynamics,  Inc.
 (1982).

      The 20 mg/kg/day  NOAEL in  the 2-year mouse study  by the  International
 Research and Development  Corporation (IRDC)  (1979) used  to calculate the
 Lifetime HA is concluded  to be  consistent with the data  in the  56-week study
 by Hazelton (1978)  in  that it is between the 30 mg/kg/day dose,  where the
 observed effect was  decreased testes/body weight ratios,  and  the 10 mg/kg/day
 NOAEL in the latter study.  Effects  on blood clotting  parameters (decrease in
 factor II times in  males  and activated partial thromboplastin times in females)
 at the 10 mg/kg/day dose  and higher  in the Hazelton  (1978) study are considered
 to be of questionable  toxicological  significance because it is  not certain
 whether they actually  represent adverse effects,  and these effects  were not
 found in the 2-year  rat study by Biodynamics (1982).

      The 16-week  and 13-week feeding  studies with R-1910 Technical  in dogs
 and rats, respectively, by Woodard Research  Corp.  (1967b,c) can  also be
 proposed for  calculation of the Longer-term  HA.   However,  the highest
 estimated dose of 45 mg/kg/day  was the NOAEL in  the  dog  study, and  the
 highest dose  of 32 mg/kg/day was the NOAEL in  the rat  study.  These NOAELs
 are also higher than the 30 mg/kg/day  dose where  testicular effects were
 evident in  the Hazelton (1978)  study in rats,  though these effects  are
 overshadowed  by the  failure to  repeat  them in  the 2-year  rat study  by
 Biodynamics  (1982),  and use of doses between  the  20 mg/kg/day NOAEL and the
 80 mg/kg/day  LOAEL in  the IRDC  (1979)  mouse  study could  have provided a closer
 comparison  of dose-response across species.  Consequently, the 20 mg/kg/day
 NOAEL in the  mouse study by IRDC (1979)  is concluded to  be an effective NOAEL
 across  species used  in presently available butylate  toxicity studies.

 Lifetime Health Advisory

      The Lifetime HA represents that portion of an individual's  total  exposure
 that  is  attributed to drinking water and  is considered protective of  noncar-
 cinogenic adverse health effects over a lifetime exposure.  The Lifetime HA
 is  derived  in a three step process,  step  1 determines the Reference  Dose
 (RfD),  formerly called the Acceptable Daily Intake (ADI).  The RfD  is an esti-
 mate  of  a daily exposure to the human population that is likely to  be without
 appreciable risk of deleterious effects over a lifetime,  and is derived  from
 the NOAEL (or LOAEL), identified from a chronic (or subchronic)  study,  divided
by  an uncertainty factor(s).   From  the RfD, a Drinking Water Equivalent Level
 (DWEL) can be determined (Step 2).   A DWEL is a medium-specific  (i.e., drinking
water) lifetime exposure level,  assuming 100% exposure from that medium, at
which adverse, noncarcinogenic health effects would not be expected to occur.
The DWEL is derived from the multiplication of the RfD by the  assumed body
weight of an adult and  divided by the assumed daily water consumption of an

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Butylate                                                        August, 1987

                                     -10-
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. EPAa, 1986), then caution should be exercised in
assessing the risks associated with lifetime exposure to this chemical.

     The 2-year feeding study on Sutan® Technical in mice by IRDC (1979) has
been selected to serve as the basis for the Lifetime HA value for butylate.
Although the NOAEL of 20 mg/kg/day is lower than the NOAEL of 50 mg/kg/day in
the 2-year feeding study with Sutan® Technical in rats by Biodynamics (1982),
the mouse study is used, following the reasons given under the Longer-term HA.

     The Lifetime HA is calculated as follows:

Step 1:  Determination of the Reference Dose (RfD)

             RfD - (20 mg/kg/day)  _ 0.07 mg/kg/day (70 ug/kg/day)
                     (100)  (3)
where:

        20 mg/kg/day = NOAEL, based on the absence of toxic signs in mice
                       exposed to butylate in the diet for 2 years..

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

                   3 = additional uncertainty factor used by EPA/Office of
                       Pesticide Programs to account for the absence of major
                       studies (chronic feeding in dogs, reproduction in
                       rats, teratology in rabbits) which does not make it
                       possible to establish the most sensitive end point for
                       butylate.

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

          DWEL = (0.07 mg/kg/day) (70 kg) = 2.45 mg/L (2,450  ug/L)
                         (2  L/day)

where:

        0.07 mg/kg/day = RfD.

                 70 kg = assumed body weight of adult.

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

Step  3:  Determination of the Lifetime Health Advisory

             Lifetime HA -  (2.45 mg/L)(20%) „ 0<05 mg/L  (50 ug/L)

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     Butylate                                                        August, 1987

                                          -11-


     where:

            2.45 mg/L - DWEL.

                  20% = assumed relative source contribution from water.

                   10 = uncertainty factor, chosen in accordance with Office of
                        Drinking Water (ODW) policy for use with Group C carcinogens.

     Evaluation of Carcinogenic Potential

          0  Available toxicity data do not determine butylate to be carcinogenic,
             although a significant (p <0.05) increase in neoplastic nodules in
             the liver of male rats fed the highest dose in the 2-year study by
             Biodynamics (1982) was found.

          0  Applying the criteria described in EPA's guidelines for assessment
             of carcinogenic risk (U.S. EPA, 1986a), butylate may be placed in
             Group C:  a possible human carcinogen.  This category is for substances
             that show limited evidence of carcinogenicity in animals and inadequate
             evidence in humans.

          0  The U.S. EPA has not calculated excess lifetime cancer risks for this
             material.


 VI. OTHER CRITERIA, GUIDANCE AND STANDARDS

          0  Residue tolerances for butylate have been established by the U.S.  EPA
             (1985) and include 0.1 ppm in or on corn grain, fresh corn, corn
             forage and fodder, sweet corn and popcorn.   A tolerance is a derived
             value based on residue levels, toxicity data, food consumption levels,
             hazard evaluation and scientific judgment,  and 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).

          0  The U.S. EPA Office of Pesticide Programs has calculated a provisional
             ADI of 70 ug/kg/day, based on the 20-mg/kg/day NOAEL in the 2-year
             mouse study by IRDC (1979) and a 300-fold uncertainty factor (used
             because of data gaps,  including a chronic feeding study in dogs, a
             reproduction study in rats and a teratology study in rabbits, in the
             total data package).


VII. ANALYTICAL METHODS

          *  Analysis of butylate is by a gas chromatographic (GC) method applicable
             to the determination of certain nitrogen- and phosphorus-containing
             pesticides in water samples -(U.S.  EPA, 1986b).  In this method,
             approximately 1 L of sample is extracted with methylene chloride.
             The extract is concentrated and the compounds are separated using
             capillary column GC.  Measurement is made using a nitrogen-phosphorus
             detector.

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      Butylate                                                        August,  1 987

                                           -12-
              The method detection limit has not been determined for butylate,  but
              it is estimated that the detection limits for analytes included in
              this method are in the range of 0.1 to 2 ug/L.


VIII. TREATMENT TECHNOLOGIES

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

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    Butylate                                                        August, 1987

                                         -13-


IX. REFERENCES

    BCPC.   1977.   British Crop Protection Council.   Pesticide Manual, 5th ed.
         Nottingham,  England:   Boots Company, Ltd.,  p. 5S3.

    Biodynamics,  Inc.*  1982.   A two-year oral toxicity/carcinogenicity study of
         R-1910 in rats.  Project no. 78-2169.  Submitted to Stauffer Chemical Co.,
         Richmond,  CA.  Unpublished final report.   MRID 00125678.

    Bova,  D.L., J.R.  DeBaun, J.C. Petersen and J.J.  Menn.  1978.*  Metabolism of
         [ethyl-14c]  Sutan in  the rat:   Balance and  tissue residue.  Stauffer
         Chemical Co., Richmond,  CA.  Unpublished  final report.   MRID 00043681.

    Casida,  J.E., R.A. Gray and H. Tilles.  1974.   Thiocarbamate sulfoxides.
         Potent,  selective and biodegradable herbicides.   Science.   184:573-574.

    Eisenbeis, S.J.,  D.L. Lynch and A.E. Hampel.  1981.  The Ames mutagen assay
         tested against herbicides and  herbicide combinations.   Soil Sci.
         131 (1):44-47.

    Gray,  R.A., and A.J. Weierich.*  1966.  Behavior and  persistence of S-ethyl-
         diisobutylthiocarbamate (Sutan) in soils.   Unpublished  study.  Stauffer
         Chemical Company, Richmond, CA.

    Hazelton Laboratories America, Inc.*  1978. Fifty-six-week  feeding study in
         rats.  Sutan Technical.   Project no. 132-135.  Submitted to Stauffer
         Chemical Co., Richmond,  CA.  Unpublished  final report.   MRID 00035843.

    Hubbell, J.P.,  and J.E. Casida.  1977.  Metabolic fate of the N,N'-dialkyl-
         carbamoyl  moiety of thiocarbamate herbicides in  rats and corn.  J. Agric.
         Food Chem.  25(2):404-413.

    IRDC.*  1979.  International Research and Development Corporation.  Sutan
         Technical.  Lifetime  oral study in mice.   Submitted to  Stauffer Chemical
         Co., Richmond, CA.  Unpublished final report.  MRID 00035844.

    Lavy,  T.L.  1974.  Mobility and deactivation of  herbicides in soil-water
         systems:  Project A-024-NEB, University of  Nebraska, Water Resources
         Research Institute.  Submitted by Shell Chemical Company,  Washington
         DC.  Available from National Technical Information Service (NTIS),
         Springfield, VA; PB-238-632.

    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.

    Meister, R.,  ed.   1983. Farm chemicals handbook.  Willoughby,  OH:  Meister
         Publishing Company.

    Murnik,  M.R.   1976.   Mutagenicity of widely used herbicides.  Genetics.  83:554.

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

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                                     -14-
Raltech.*  1979.   Project nos.  74489 and 733422.  Submitted to Stauffer Chemice)
     Co., Richmond,  CA.   Unpublished final report.

Scholler, J.*  1976.  Fifteen-week oral (diet) toxicity study with Sutan
     Technical and Analytical in male rats:   Experiment 7.  Unpublished final
     report.   MRID 00021844.

Shell Development Company.*  1975.  Dissipation of Bladex herbicide and Sutan
     in soil  following application of Bladex,  Sutan, or a tank mix of Bladen
     and Sutan:   TIR-24-134-74.  Unpublished study.

Sleight, B.H., ill.*  1973.  Exposure of fish to He-labeled Sutan: Accumulation,
     distribution, and elimination of 14c residues. Unpublished study prepared
     by Bionomics, Inc.,  submitted by Stauffer Chemical Company, Richmond, CA.

Stauffer Chemical Company.*  1975a.  Dissipation of Bladex herbicide and  Sutan
     in soil  following application of Bladex,  Sutan, or a tank mix of Bladex
     and Sutan:   TIR-24-134-74.  Unpublished study submitted by Stauffer
     Chemical Company, Richmond, CA.

Stauffer Chemical Company.*  1975b.  Residues from Sutan on soil:  FSDS Nos.
     A-9229,  A-9229-1, A-9229-2, A-10366.  Unpublished study by Stauffer
     Chemical Company, Richmond, CA.

Stauffer Chemical Company.*  1975c.  Soil residue data of Sutan combinations
     and R-25788:  FSDS Nos.  A-9229, A-9229-1, A-9229-2, A-10366. Unpublished
     study by Stauffer Chemical Company, Richmond, CA.

Stauffer Chemical Company.*  1983.  A teratology study in CD rats with Sutan
     Technical.  Project no.  T-11713.  Unpublished final report by Stauffer
     Chemical Company, Richmond, CA.  MRID 000131032.

STORET.  1987.

Thomas, D.B., J.B. Miaullis,  A.R. Vispetto and J. Osuna.*  1979.  Metabolism
     of  [isobutyl-14C] Sutan in the rat:  Balance and tissue residue study.
     Stauffer Chemical Co., Richmond, CA.  Unpublished final report.  MRID
     00043680.

Thomas, D.LtB., J.C. Petersen and J.R. DeB=iun.*  1980.  Metabolism of
      [1-14C-ethyl] Sutan in the rat:  Urinary metabolite identification.
     Stauffer Chemical Co., Richmond, CA.  Unpublished final report.  MRID
     00043682.

Thomas, V.M., and C.L. Holt.*  1979.  Behavior of Sutan in the environment:
     MRC-B-76; MRC-78-02.  Unpublished study submitted by Stauffer Chemical
     Company, Richmond, CA.

Thomas, V.M., C.L. Holt and P.A. Bussi.*  1978.   Anaerobic soil metabolism
     of Sutan selective herbicide:  MRC-B-98; MRC-79-13.  Unpublished study
     submitted by Stauffer Chemical Comapny, Richmond, CA.

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                                     -15-
U.s. EPA.  1985.  U.S. Environmental Protection Agency.  Residue tolerances
     for S-ethyl-diisobutyl thiocarbamate.  CFR 180.232.  July 1. p. 294.

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

U.S. EPA.  1986b.  U.S. Environmental Protection Agency.  U.S. EPA method #1
     - Determination of nitrogen and phosphorus containing pesticides in
     ground water by GC/NPD,  January 1986 draft.   Available from U.S. EPA's
     Environmental Monitoring and Support Laboratory, Cincinnati, OH.

Weidner, C.W.*  1974.  Degradation in groundwater and mobility of herbicides.
     Master's thesis, University of Nebraska, Department of Agronomy.
     Unpublished study submitted by Shell Chemical Company, Washington, DC.

Woodard Research Corporation.*  1967a.  R-1910 6-E.  Subacute dermal toxicity.
     21-Day experiment with rabbits.  Submitted to Stauffer Chemical Co.,
     Richmond, CA.  Unpublished final report.  MRID 00026312.

Woodard Research Corporation.*  1967b.  R-1910.  Safety evaluation by dietary
     feeding to rats for 13.weeks.  Submitted to Stauffer Chemical Co.,
     Richmond, CA.  Unpublished final report.  MRID 00026313.

Woodard Research Corporation.*  1967c.  R-1910.  Safety evaluation by dietary
     feeding to dogs for 16 weeks.  Submitted to Stauffer Chemical Co.,
     Richmond, CA.  Unpublished final report.  MRID 00026314.

Woodard Research Corporation.*  1967d.  R-1910.  Safety evaluation by
     teratological study in the mouse.  Submitted to Stauffer Chemical Co.,
     Richmond, CA.  Unpublished final report.  MRID 000129544.
Confidential Business Information submitted to the Office of Pesticide
 Programs.

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