820K88011                            August'  1987
                                    FENAMIPHOS

                                  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 ^ble 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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    Fenamiphos
                             August,  1987
II.  GENERAL INFORMATION AND PROPERTIES
    CAS  No.   22224-92-6
    Structural  Formula
                                        -2-
                       CH3S
VX    °  H
>\    II  I
 XV0-P-N-CH(CH,)2
      OC2H$
         (1-Methylethyl)-ethyl-3-methyl-4-(methylthio)phenyl-phosphoramidate

    Synonyms

         0  Nemacur; B 68138; Bay 68138; Bayer 68138; ENT 27572; Phenamiphos
            (Meister, 1983).

    Uses

         0  Systemic nematicide (Meister, 1983).

    Properties   {Meister, 1983)
           Chemical Formula
           Molecular Weight
           Physical State (at 25°C)
           Boiling Point
           Melting Point
           Density
           Vapor Pressure (30°C)
           Water Solubility (25°C)
           Log Octanol/Water Partition
              Coefficient
           Taste Threshold
           Odor Threshold
           Cor version Factor
        C13H22°3NSP
        303  (calculated)
        Brown, waxy solid

        49.2°C

        7.5  x 1C~7 ran Hg
        400  ng/L
    Occurrence
           Fenamiphos has been found in only 2 ground water samples out of
           452 analyzed  (STORET, 1987).  Both locations were in California with
           the highest concentration found being 5 ug/L.   No surface water
           locations were tested.

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Fenamiphos                                                  August,  1987

                                     -3-


Environmental Fate

     0  Ring-labeled 14c-fenamiphos {radiochemical purity 94%), at 1  and 10 ppm,
        degraded with half-lives of 7 to 1 4 days in a buffered aqueous solution
        at pH 3 and >30 days at pH 9, and appeared to be stable at pH 7 when
        incubated in the dark at 30°C (McNamara and Wilson,  1981).  In the
        pH 3 buffer solution, the primary degradation product was deaininated
        fenamiphos accounting for 74 to 78% of the applied material.   Degradates
        identified in methylene chloride extracts from the pH 3, 7 and 9
        solutions included fenamiphos sulfoxide, fenamiphos  sulfone,  fenamiphos
        phenol, fenamiphos sulfoxide phenol and fenamiphos sulfone phenol.

     0  Ring-labeled 1^C-fenamiphos (radiochemical purity >99%), at 12 ppm,
        degraded with a half-life of 2 to 4 hours in pH 7 buffered water
        irradiated with artificial light (approximately 5200 uW/cm2,  300 to
        600 nm) (Dime et al., 1983).  After 24 hours of irradiation,  fenamiphos
        accounted for approximately 4% of the applied radioactivity,  fenamiphos
        sulfonic acid phenol for approximately 19%, fenamiphos sulfoxide for
        approximately 17%, fenamiphos sulfonic acid for approximately 6% (tenta-
        tive identification), and fenamiphos sulfoxide phenol for approximately
        1%.  In the dark control, fenamiphos accounted for approximately 94% of
        the applied at 24 hours post-treatment.

     0  Ring-labeled 14c-fenamiphos (radiochemical purity >99%), at approxi-
        mately 20 ppm, degraded with a half-life of <1 hour on sandy  loam soil
        irradiated with artificial light (approximately 6200 uW/cm2,  300 to
        600 nm) (Dime et al., 1983).  After 48 hours of irradiation,  fenamiphos
        and the degradates fenamiphos sulfoxide and fenamiphos sulfone accounted
        for approximately 12, 55 and 6% of the extractable radioactivity,
        respectively.  In the dark control, fenamiphos accounted for  approxi-
        mately 93% of the extractable compound at 48 hours post-treatment.

     0  14c-Fenamiphos (purity 86%), at 3 ppm, degraded with a half-life of
        <4 days in silty clay loam soil previously treated with fenamiphos
        (Green et al., 1982).  Fenamiphos sulfoxide comprised up to approxi-
        mately 74% of the applied radioactivity (maximum at 11 days post-
        treatment); fenamiphos sulfone comprised approximately 10% and volatile
        14c-residues comprised 17% of the applied material at 55 days post-
        treatment.  At 55 days post-treatment, 1.13% of the applied fenamiphos
        remained undegraded in the soil previously treated with fenamiphos,
        5.41% remained undegraded in soil with no prior history of fenamiphos
        treatment, and 40.58% remained undegraded in sterile soil.  Fenamiphos
        sulfoxide was the major degradate in all three treatments.

     o  14c-Fenamiphos (test substance uncharacterized), at 0.29 to 2.30 ug/ml
        of water, was adsorbed to sandy loam and clay loam soils with 26.3 to
        30.0% and 42.2 to 52.3% of the applied radioactivity, respectively,
        adsorbed after 16 hours (Church, 1970).

     0  Fenamiphos (3 lb/gallon SC and 15% G), at approximately 20 Ib ai/A,
        was mobile in columns (16-cm length) of sandy soil eluted with 10
        inches of water.  Fenamiphos was detected throughout the columns, and
        0.9 to 2.2% of the applied material was recovered in the leachate
        (Gronberg and Atwell, 1980).

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     Fenamiphos                                                  August,  1987

                                          -4-
          0  Aged (30 days)  14C-fenamiphos  residues,  at approximately 4 Ib ai/A,
             were slightly mobile  in a column  (12-inch length)  of sandy loam soil
             leached  with  22.5 inches of  water;  approximately 2.3% of the applied
             radioactivity leached from the column and approximately 91% of the
             applied  radioactivcity remained in  the top 5 inches of the soil
             column (Tweedy  and Houseworth,  1980).


III. PHARMACOKINETICS

     Absorption

          0  Gronberg (1969) administered 14C-labeled fenamiphos (99% purity)
             by oral  intubation to rats.   Only 5 to 7% was recovered in feces,
             indicating that 93 to 95% was  absorbed from the gastrointestinal
             tract.

     Distribution

          0  Gronberg (1969) administered single oral doses of 2 mg/kg of ethyl-
             14C-fenamiphos  (99% purity)  by oral intubation to rats.  Forty-eight
             hours after treatment, residues measured in tissues were:  brain
             <0.1 ppm; heart 0.1 ppm; liver 0.8 to 1.7 ppm; kidney 0.4 to 0.5 ppm;
             fat 0.2  to 0.4  ppm; muscle <0.1 ppm; and gastrointestinal tract 0.2 ppm.

     Metabolism

          0  In studies conducted  by Gronberg  (1969), rats were administered 2 mg/kg
             oral doses of fenamiphos  (99% purity) using ethyl-14c, methylthio-3H or
             isopropyl-14C label.   The authors proposed a pathway of fenamiphos
             metabolism involving  oxidation to the sulfoxide and sulfone analogs.
             Subsequent hydrolysis, conjugation and excretion via urine gave high
             molecular-weight compounds (600 to 800).  No other details were
             provided.
     Excretion
             Gronberg (1969) administered ethyl-14c, methylthio-3H or isopropyl-
             14c-labeled fenamiphos (2 mg/kg, 99% purity) to rats by gavage.
             Thirty-nine to forty-two percent or 50% of the administered radio-
             activity was expired as CO2, respectively.  Thirty-eight to 40% of
             the ethyl-14c labels were in urine and 5% in feces, respectively.
             Eighty percent of the methylthio-^H label was found in urine.  The
             majority of the administered dose was excreted 12 to 15 hours after
             treatment.
 IV. HEALTH EFFECTS
     Humans
           0  No information on the health effects of fenamiphos in humans was
             found in the available literature.

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Fenamiphos                                                  August,  1987

                                     -5-


Animals

   Short-term Exposure

     0  NIOSH (1985) reported the acute oral LD$Q of fenamiphos in the rat,
        mouse, dog, cat,  rabbit and guinea pig as 8, 22.7,  10,  10, 10 and
        75 mg/kg,  respectively.

     0  Kimmerle and Lorke (1970) fed chickens (eight/dose) diets containing
        technical  fenamiphos at levels of 0, 1, 3, 10 or 30 ppm active
        ingredient (a.i.) for 30 days.  The authors stated  that this corre-
        sponded to doses  of 0,  2, 5,  16 or 26 mg/kg/day.  Following  treatment,
        feed consumption, neurotoxicity and cholinesterase (ChE) activity
        were determined.   Histopathological sections of the brain, spinal
        cord and peripheral nerves were also evaluated.  No neuropathy was
        observed at any dose level tested.  No ChE symptoms were reported,
        but ChE activity  in whole blood was inhibited in a  dose-dependent
        manner from 21% at 3 ppm to 65% at 30 ppm.  Based on ChE inhibition,
        a No-Observed-Adverse-Effect-Level (NOAEL) of 1 ppm (2  mg/kg/day) was
        identified.

   Dermal/Ocular Effects

     0  DuBois et al. (1967) reported acute dermal LD5Q values  of 78 mg/kg
        for rats and 55 mg/kg for guinea pigs.

     0  Crawford and Anderson (1973)  applied 120 mg of a spray  concentrate of
        fenamiphos (37.47% a.i.) to shaved intact and abraded skin of six New
        Zealand White rabbits and reported slight erythema  24 and 72 hours
        post-treatment.

     0  In ocular studies conducted by Crawford and Anderson (1973), the
        instillation of 0.1 mL of a spray concentrate of fenamiphos (37.47%
        a.i.) into the eyes of New Zealand White rabbits resulted in corneal
        and conjunctival  damage at 24 and 72 hours post-treatment.  These
        effects had not subsided by 21 days post-treatment.

   Long-term Exposure

     0  In feeding studies conducted by Mobay Chemical Corporation (1983),
        Fischer 344 rats  (50/sex/dose) were administered technical fenamiphos
        (89% purity) at dose levels of 0, 0.36, 0.60 or 1.0 ppm a.i. for
        90 days.  Assuming that 1 ppm in the diet of rats is equivalent to
        0.05 mg/kg/day (Lehman, 1959), this corresponds to dose levels of 0,
        0.018, 0.03 or 0.05 mg/kg/day.  Following treatment, brain,  plasma
        and erythrocyte ChE levels were measured.  Cholinesterase levels were
        not significantly reduced at any dose tested.  Other parameters were
        not evaluated.  The author reported a NOAEL of 1 ppm (0.05 mg/kg/day,
        the highest dose  tested).

     0  Loser and Kimmerle (1968) fed Wistar rats (15/sex/dose) fenamiphos
        for 90 days in the diet at dose levels of 0, 4, 8,  16 or 32 ppm
        active ingredient.  Assuming that 1 ppm in the diet is  equivalent to

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Fenamiphos                                                  August,  1987

                                     -6-
        0.05 mg/kg/day (Lehman,  1959),  this corresponds  to doses of 0,  0.2,
        0.4, 0.8 or 1.6 mg/kg/day.   Following treatment,  body weight,  food
        consumption,  hematology,  ChE activity,  urinalysis and gross pathology
        were evaluated.  No histologic  examination was performed.   No  effects
        on any end point were reported  except for ChE inhibition.   No  effect
        was seen at 4 ppm (0.2 mg/kg/day).   At 8 ppm  (0.4 mg/kg/day),  ChE in
        whole blood and plasma was  decreased by 11% and  19%,  respectively.
        Higher doses produced larger decreases in ChE.   Based on these  data,
        a NOAEL of 4 ppm (0.2 mg/kg/day)  was identified.

     0  Loser (1970) administered technical fenamiphos  (99.4% purity)  in the
        feed of beagle dogs (two/sex/dose)  for 3 months  at dietary levels of
        0, 1, 2 or 5 ppm.  Assuming that  1  ppm in the diet of dogs is  equivalent
        to 0.025 mg/kg/day (Lehman, 1959),  this corresponds to doses of 0,
        0.025, 0.05 or 0.125 mg/kg/day.  Untreated controls (three/sex) were
        run concurrently.  Following treatment, body  weight,  feed consumption,
        clinical chemistry, urinalysis, ChE activity  and gross pathology were
        evaluated.  At 5 ppm, there was some slight decrease in weight gain,
        although the author did  not consider this to  be  important.  No compound-
        related effects were reported in  any other parameters measured except
        ChE activity.  At 1 ppm,  plasma ChE was inhibited 13% and 18%,  and
        red blood cell ChE was inhibited  6% and 19% in males and females,
        respectively.  At 2 ppm,  plasma and red blood cell ChE was comparable
        to control levels in males, and was inhibited 13% in plasma and 15%
        in red blood cells in females.  At  5 ppm, ChE in plasma was inhibited
        44% and 41%,and red blood cell  ChE  was inhibited 22% and 26% (females
        and males, respectively).  No brain ChE measurements were reported.
        Based on the absence of  significant (>20%) ChE inhibition at 1  or
        2 ppm, a NOAEL of 2 ppm  (0.05 mg/kg/day) is identified.

     0  Hayes et al.  (1982) administered  fenamiphos (90% purity) in the diet
        to CD albino mice (50/sex/dose) at  dose levels  of 0, 2, 10 or 50 ppm
        for 18 months.  Assuming that 1 ppm in the diet  of mice is equivalent
        to 0.15 mg/kg/day (Lehman,  1959), this corresponds to doses of 0, 0.3,
        1.5 or 7.5 mg/kg/day.  Following  treatment, body weight, food con-
        sumption, hematology and mortality  were evaluated.  Absolute brain
        weights were decreased at 2 ppm (0.3 mg/kg/day)  or greater.  At 50 ppm
        (7.5 mg/kg/day), there was a decrease in body weight.  Based on these
        data, a Lowest-Observed-Adverse-Effect-Level  (LOAEL) of 2 ppm  (0.3
        mg/kg/day), lowest dose  tested, was identified,  but not a NOAEL.

     0  Lo.ser  (1972a) administered technical fenamiphos   (78.8% purity) in the
        diet of Wistar rats  (40/sex/dose) for 2 years at dose levels of 0, 3,
        10 or 30 ppm a.i.  Assuming that  1  ppm in the diet of rats is equiva-
        lent to 0.05 mg/kg/day (Lehman, 1959), this corresponds to doses of
        0, 0.15, 0.5 or  1.5 mg/kg/day.   Untreated controls (50 males,  60
        females) were run concurrently.  Following treatment, body weight,
        food consumption, hematology, urinalysis, plasma and erythrocyte ChE
        activity, gross pathology and histopathology  were evaluated.  At the
        highest dose  (30 ppm), a slight increase in female mortality (38%
        versus 29% in controls)  was noted,  but the author did not consider
        this significant.  Ihere were statistically significant (p <0.05)
        increases in thyroid gland and lung weights in females and in heart

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Fenamiphos                                                  August,  1987

                                     -7-
        weight in  males.   No  compound-related  effects  were observed in any of
        the other  parameters  measured  except an  inactivation  of  plasma and
        erythrocyte ChE.   At  10  ppm, ChE  was decreased by  18  to  41%,  and  at
        30 ppm,  ChE was decreased  by 28 to  60%.   No  brain  ChE measurements
        were reported.  Based on ChE inhibition,  the author identified a  NOAEL
        of 3 ppm (0.15 mg/kg/day).  Based on organ weight  changes,  the NOAEL
        was 10 ppm (0.5 mg/kg/day).

     0   In chronic feeding studies by  Loser (1972b), beagle dogs (four/sex/dose)
        were administered  technical fenamiphos (78.8%  purity) in the  feed for
        2 years at 0, 0.5,  1,  2, 5 or  10  ppm active  ingredient.   Assuming
        that 1  ppm in the  diet of  dogs  is equivalent to  0.025 mg/kg/day (Lehman,
        1959),  this corresponds  to doses  of 0, 0.013,  0.025,  0.050,  0.125 or
        0.250 mg/kg/day.   Following treatment, no compound-related  effects
        were observed on appearance, general behavior, food consumption,
        clinical chemistry, hematology, gross  pathology  or histopathology at
        any dose tested.   Plasma and erythrocyte  ChE levels were inhibited
        about 26%  at 2 ppm, about  21 to 57% at 5  ppin and about 32 to  51%  at
        10 ppm.  Cholinesterase  was not inhibited at 1 ppm (0.025 mg/kg/day)
        or below.  Based on ChE  inhibition,  this  study identified a NOAEL of
        1  ppm (0.025 mg/kg/day)  and a  LOAEL of 2  ppm (0.05 mg/kg/day).

   Reproductive Effects

     0   In a three-generation study conducted  by  Loser (1972c),  FB30  rats
        (10 males  or 20 females/dose)  were  fed technical fenamiphos  (78.8%)
        in the  diet at dose levels of  0,  3,  10 or 30 ppm active  ingredient.
        Assuming that 1 ppm in the diet of  rats is equivalent to 0.05 mg/kg/day
        (Lehman, 1959), this  corresponds  to doses of 0,  0.15,  0.5 or  1.5
        mg/kg/day.  Fertility, lactation  performance, pup development and
        parental and litter body weights  were  evaluated.   No  compound-related
        effects  were observed in any parameter in animals  exposed to  10 ppm
        (0.5  mg/kg/day) or  less.  At 30 ppm  (1.5  mg/kg/day),  one male of  the
        F2b generation showed a  lower body  weight gain than the  untreated
        controls, but there were no differences in body  weight gain in any
        other generation.   Based on these data, a reproductive NOAEL  of 30
        ppm (1.5 mg/kg/day) was  identified.

   Developmental Effects

        MacKenzie et al. (1982) administered fenamiphos  (88%  a.i. by  gavage
        to pregnant New Zealand white rabbits  (20/dose)  at dose  levels of  0,
        0.1,  0.3 or 1.0 mg/kg/day on days 6  to 18 of gestation.  Following
        treatment,  there was a decrease in maternal body weight  at 0.3 mg/kg/day
        or above.  At the 1,0-mg/kg/day level,  eight dead pups and seven  late
        resorptions were reported,  and  fetal weight was depressed.  A signifi-
        cant  (p  <0.05)  increase in the incidence of chain-fused  sternebrae
        was also observed at 1.0 mg/kg.  Based on maternal body weight, a
        NOAEL of 0.1  mg/kg was identified.  Based on fetotoxicity and terato-
        genicity, a NOAEL of 0.3 mg/kg/day was identified.

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   Fenamiphos                                                  August,  1987

                                        -8-


      Mutagenicity

        0  Herbold (1979)  reported  that  fenamiphos  was  not mutagenic  in Salmonella
           typhimurium (TA 1535,  1537, 98  or  100) up to 2,500 ug/plate,  either
           with or without activation.

        0  In  a dominant lethal  test with  male  mice (Herbold and Lorke,  1980),
           acute oral doses of 5  mg/kg did not  produce  mutagenic effects.

      Carcinogenicity

        0  Hayes et al.  (1982) administered fenamiphos  (90% purity) for 18 months
           in  the diet to CD albino mice (50/sex/dose)  at dose levels  of 0,  2,  10
           or  50 ppm (0, 0.3,  1.5 or  7.5 mg/kg/day). Based on gross  and histo-
           pathologic examination,  neoplasms  in various tissues and organs were
           similar in type, organization,  time  of occurrence and incidence in
           control and treated animals.

        0  Loser (1972a) administered  technical fenamiphos  (78.8%  purity) in the
           diet of Wistar rats  (40/sex/dose)  for 2  years at dose levels of 3, 10
           or  30 ppm active ingredient.  Assuming that  1 ppm in the diet of  rats
           is  equivalent to 0.05 mg/kg/day (Lehman, 1959), this corresponds  to
           doses of 0.15,  0.5 or 1.5  mg/kg/day.  Untreated controls  (50 males,
           60  females) were run  concurrently.   No evidence of Carcinogenicity
           was detected either by gross  or histological examination.


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.

                       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 by a child
                            (1 L/day) or an adult (2 L/day).

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Fenamiphos                                                  August,  1987

                                     -9-


One-day Health Advisory

     No information was found in the available literature that was suitable
for determination of the One-day HA value for fenamiphos.  It is therefore
recommended that the Ten-day HA value for the 10-kg child of 0.009 mg/L (9 ug/L,
calculated below) be used at this time as a conservative estimate of the
One-day HA value.

Ten-day Health Advisory

     The study by MacKenzie et al. (1982) has been selected to serve as the
basis for determination the Ten-day HA value for fenamiphos.  In this study,
pregnant rabbits (20/dose) were administered technical fenamiphos (88% purity)
by gavage at dose levels of 0, 0.1, 0.3 or 1.0 mg/kg on days 6 through 18 of
gestation.  A decrease in maternal body weight was observed in animals dosed
with 0.3 mg/kg/day or above.  No maternal toxicity was reported at 0.1 mg/kg/day.
No fetotoxicity or teratogenic effects were observed at 1.0 mg/kg or less or
0.3 mg/kg or less, respectively.  Chain fusion of sternebrae were observed in
the 1.0 mg/kg group.  Based on maternal effects, a NOAEL of 0.1 mg/kg/day was
identified.

     Using a NOAEL of 0.1 mg/kg/day, the Ten-day HA for a 10-kg child is
calculated as follows:

      Ten-day HA = (0'1 mg/kg/day) (10 kg) (0.88) = 0>009   /L (9    „ }
                            (100) (1 L/day)

where:

        0.1 mg/kg/day = NOAEL, based on absence of maternal or fetal toxicity
                        in rabbits exposed to fenamiphos via gavage on days
                        6 through 18 of gestation.

                1 0 kg = assumed body weight of a child.

                 0.88 = correction factor to account for 88% active ingredient
                        in administered doses.

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

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

Longer-term Health Advisory

     The study by Loser (1970) has been selected to serve as the basis for
determination of the Longer-term HA value for fenamiphos.  In this study,
beagle dogs (two/sex/dose) were fed technical fenamiphos (99.4% purity)  in
the diet at dose levels of 0,  1, 2 or 5 ppm  (0,  0.025,  0.05 or 0.125 mg/kg/day)
for 3 months.  No effects were detected on body weight, food consumption,
clinical chemistry,  urinalysis and gross pathology.   The only effect observed
was inhibition of plasma and erythrocyte ChE activity at the 5-ppm dose
level (0.125 mg/kg/day).  No significant effect was  seen at 2 ppm or less

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Fenamiphos                                                  August,  1987

                                     -10-
(0.05 mg/kg/day), which was identified as the NOAEL.   The 90-day study in
F344 rats by Mobay Chemical Corporation (1983) identified a NOAEL of 1 ppm
(0.05 mg/kg/day), but this was not considered, since it was the highest dose
tested and a LOAEL was not identified.  The study by Loser and Kimmerle
(1968) identified a NOAEL of 0.2 mg/kg/day in rats,  but this was not chosen,
since available data (Loser et al., 1972a,b) suggest that the rat is less
sensitive than the beagle dog.

     Using a NOAEL of 0.05 mg/kg/day,  the Longer-term HA for a 10-kg child is
calculated as follows:

       Longer-term HA = (0.05 mg/kg/day) (10 kg) = Oi005   /L (5   /L)
                            (100)  (1  L/day)

where:

        0.05 mg/kg/day =  NOAEL, based on absence of significant cholinesterase
                          inhibition in dogs exposed to fenamiphos via the diet
                          for 3 months.

                 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 by a child.

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

       Longer-term HA = (.°'05 mg/kg/day) (70 kg) = 0>01Q   /L (1Q   /L)
                            (100)  (2 L/day)

where:

        0.05 mg/kg/day =  NOAEL, based on absence of significant cholinesterase
                          inhibition in dogs exposed to fenamiphos via the diet
                          for 3 months.

                 70 kg = assumed body weight of an adult.

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

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

Lifetime Health Advisory

     The Lifetime HA represents that portion of an individual's total exposure
that is attributed to drinking water and is considered protective of noncar-
cinogenic adverse health effects over a lifetime exposure.  The Lifetime HA
is derived in a three-step process.  Step  1 determines the Reference Dose
 (RfD), formerly called the Acceptable Daily Intake (ADI).  The RfD is an esti-
mate  of a daily exposure to the human population that is likely to be without

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Fenamiphos                                                  August,  1987

                                     -1 1-
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.  From the RfD,  a Drinking Water Equivalent Level
(DWEL) can be determined (Step 2).   A DWEL is a medium-specific (i.e., drinking
water) lifetime exposure level, assuming 100% exposure from that medium, at
which adverse, noncarcinogenic health effects would not be expected to occur.
The DWEL is derived from the multiplication of the RfD by the assumed body
weight of an adult and divided by the assumed daily water consumption of an
adult.  The Lifetime HA is determined in Step 3 by factoring in other sources
of exposure, the relative source contribution (RSC).  The RSC from drinking
water is based on actual exposure data or, if data are not available, a
value of 20% is assumed for synthetic organic chemicals and a value of 10%
is assumed for inorganic chemicals.  If the contaminant is classified as a
Group A or B carcinogen, according to the Agency's classification scheme of
carcinogenic potential (U.S. EPA, 1986), then caution should be exercised in
assessing the risks associated with lifetime exposure to this chemical.

     The study by Loser  (1972b) has been selected to serve as the basis for
determination of the Lifetime HA value for fenamiphos.  In this study, dogs
(four/sex/dose) were fed technical fenamiphos (78.8% purity) in the diet for
2 years at dose levels of 0, 0.5, 1, 2, 5 or 10 ppm active ingredient  (0,
0.013, 0.025, 0.05, 0.125 or 0.25 mg/kg/day).  The only effect detected was
inhibition of plasma and erythrocyte cholinesterase at dose levels of  2, 5 or
10 ppm (0.05, 0.125 or 0.25 mg/kg/day).  The NOAEL identified in this  study
was 1 ppm (0.025 mg/kg/day).  The chronic studies in rats by Loser (1972a)
and by Hayes et al.  (1982) were not chosen, since the data indicate the rat
is less sensitive than the dog.

     Using a NOAEL of 0.025 mg/kg/day, the Lifetime HA is calculated as follows:

Step 1:  Determination of the Reference Dose  (RfD)

                  RfD =  (0.025 mg/kg/day) = Q.00025 mg/kg/day
                              (100)
where:

     0.025 mg/kg/day = NOAEL, based on absence of cholinesterase inhibition
                       in dogs exposed to technical fenamiphos via the diet
                       for 2 years.

                 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 = 0-00025 mg/kg/day)  (70 kg) = 0.009 mg/day  (9 ug/L)
                          (2 L/day)
where:

        0.00025 mg/kg/day = RfD.

                     70 kg = assumed body weight of an adult.

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

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      Fenamiphos                                                   August,  1987

                                           -12-


      Step 3:   Determination  of  the  Lifetime  Health  Advisory

             Lifetime  HA  =  (0.009 mg/L)  (20%)  =  0.0018 mg/L  (1.8 ug/L)

      where:

              0.009 mg/L  =  DWEL.

                     20%  =  assumed  relative source contribution  from  water.

      Evaluation  of Carcinogenic Potential

           0   No  evidence of  carcinogenic potential  was  detected in chronic  feeding
              studies  in  rats (Loser,  1972a)  or  mice (Hayes  et al., 1982).

           0   The International  Agency for  Research  on Cancer  has  not evaluated the
              carcinogenic  potential of  fenamiphos.

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


  VI.  OTHER CRITERIA,  GUIDANCE AND  STANDARDS

           0   Residue  tolerances have  been  established for fenamiphos and  its
              cholinesterase-inhibiting  metabolites  in or  on various  agricultural
              commodities at  0.02 to 0.60 ppm based  on an  ADI  for  fenamiphos
              of  0.0025 mg/kg/day  (U.S.  EPA,  1985).

           0   The World Health Organization (WHO)  calculated a TADI of  0.0003
              nig/kg/day for fenamiphos (Vettorazzi and Van den Hurk,  1985).


 VII.  ANALYTICAL  METHODS

           0   There is no standarized  method  for the determination of fenamiphos
              in  water samples.  A  procedure  has been reported for the  estimation
              of  fenamiphos and  other  pesticides in  foods  and  feeds (FDA,  1979).
              This procedure  involves  extraction and isolation in  an  organic phase/-
              the extract is  then dried  and concentrated,  and  an aliquot of  the
              concentrated  organic  phase is injected into  a  gas  chromatograph
              equipped with a phosphorus-selective detector.


VIII.  TREATMENT TECHNOLOGIES

           0   No  information  was found in the available  literature on treatment
              technologies  used  to  remove fenamiphos from  contaminated water.

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    Fenamiphos                                                  August,  1987

                                         -1 3-


IX. REFERENCES

    Church,  D.D.*  1970.   Bay 68138 — leaching,  runoff,  and water stability.
         Report No.  26849.   Unpublished study received May 27,  1970 under OF0982;
         submitted by Chemagro Corp.,  Kansas City, MO; CDL:091690-H.  MRID 00067117.

    Crawford,  C., and R.  Anderson.*  1973.   The eye and skin irritancy of Nemacur
         3 Ibs/gal spray  concentrate to rabbits.   Report No. 37549.  Unpublished
         study.  MRID 00119227.

    Dime, R.A., C.A.  Leslie and R.J. Puhl.*  1983.  Photodecomposition of Nemacur
         in aqueous  solution and on soil.  Report No. 86171.  Mobay Chemical Corp.
         1983.  Supplement No. 4 to brochure entitled:  Nemacur:  The effects on
         the environment  — environmental chemistry (dated Feb. 1, 1973).  Document
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    DuBois,  K.P., M.  Flynn and F. Kinoshita.*  1967.  The acute toxicity and anti-
         cholinesterase action of Bayer 68138.  Unpublished study.  MRID 00082807.

    FDA.  1979.  Food and Drug Administration.  Pesticide analytical manual.
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    Green, R., C. Lee and W. Apt.*  1982.  Processes affecting pesticides and
         other organics in soil and water systems:  Assessment of soil and
         pesticide properties important to the effective application of nematicides
         via irrigation.   Hawaii contributing project to Western Regional Research
         Project W-82.  Unpublished study.   MRID 00154533.

    Gronberg,  R.R.*   1969.   The metabolic fate of (Bay 68138),  (Bay 68138 sulfoxide),
         and (Bay 68138 sulfone) by white rats.  Report No. 26759.  Unpublished
         study.  MRID 00052527.

    Gronberg,  R.R.,  and S.H. Atwell.*  1980.  Leaching of Nemacur residues in
         Florida sand.  Report No. 66409.  Rev.  Unpublished study received Aug. 28,
         1980 under  3125-236; submitted by Mobay Chemical Corp., Kansas City, MO;
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    Hayes, R.H., D.W. Lamb and D.R. Ma'llicoat. *  1982.  Technical fenamiphos
         oncogenicity study in mice.  Report No.  3037.  Unpublished study.
         MRID 00098614.

    Herbold, B.*  1979.   Nemacur:  Salmonella/microsome test for detection of
         Point-mutagenic  effects:  Report No. 8730; 82210.  Unpublished study.
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    Herbold, B., and D. Lorke.*  1980.  SRA 3386:  Dominant lethal study on male
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    Kimmerle,  G., and D.  Lorke.*  1970.  Bay 68138:  Subchronic neurotoxicity
         studies on  chickens.  Report No. 1831; 27489.  Unpublished study.
         MRID 00082105.

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Fenamiphos                                                   August, 1987

                                     -14-
Lehman, A.J.  1959.  Appraisal of the safety of chemicals in foods, drugs and
     cosmetics.   Assoc. Food Drug Off.

Loser, E.*  1970.  Bay 68138:   Subchronic toxicological studies on dogs (three
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Loser, E.*  1972a.  Bay 68138:  Chronic toxicological studies on rats (two-year
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Loser, E.*  1972b.  Bay 68138:  Chronic toxicological studies on dogs (two-year
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Loser, E.*  1972c.  Bay 68138:  Generation studies on rats.  Report No. 3424;
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Loser, E., and G. Kimmerle.*  1968.  Bay 68138:  Subchronic toxicological study
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MacKenzie, K., S. Dickie, B. Mitchell et al.*  1982.  Teratology study with
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McNamara,  F.T.,  and C.M. Wilson.*  1981.  Behavior of Nemacur in buffered
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Meister, R., ed.  1983.  Farm chemicals handbook.  Willoughby,  OH:  Meister
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Mobay Chemical Corporation.*  1983.  Combined  chronic toxicity/oncogenicity
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NIOSH.  1985.  National Institute for Occupational Safety and Health.  Registry
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Tweedy, E.G., and L.D. Houseworth.*  1980.  Leaching of aged Nemacur residues
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U.S.  EPA.   1979.  U.S. Environmental Protection Agency.  Summary of reported
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U.S.  EPA.   1985.  U.S. Environmental Protection Agency.  Code of Federal
     Regulations.  40 CFR  180.349, p. 324.  July 1,  1985.

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Fenamiphos                                                   August, 1987

                                     -15-
U.S. EPA.  1986.  U.S. Environmental Protection Agency.  Guidelines for
     carcinogen risk assessment.  Fed. Reg.  51(1 85): 33992-34003.
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Vettorazzi, G., and G.W. Van den Hurk.  1985.  Pesticides reference index,
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*Confidential Business Information.

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