August, 1987

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

       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

       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 accuratel'' than another.
   Because each model is based on differing assumptions, the estimates that are
   derived can differ by several  orders  of magnitude.

    Methyl Parathion
                                                              August,  1987

    CAS No.   298-00-0

    Structural Formula
                 0,0-Dimethyl-0-(4-nitrophenyl) phosphorothioic  acid
         0   Metron;  Meptox;  Metaphos;  Dimethyl  parathion;  Nitrox;  Azofos;  Nitrox 80;
            BAY 11405;  Metacide;  Folidol M; Azophos; Methyl-E 605;  Dalf;  Meticide;
            Methylthiophos;  Pencap M;  Penncap M;  Sinafid M-48; Wofotox;  Vofatox;
            Thiophenit; Wofatox  (Meister,  1983).
         0   A  restricted-use pesticide for control of various insects  of  economic
            importance; especially effective  for boll weevil control  (Meister,  1983),

    Properties   (Hawley,  1981; Meister,  1983; CHEMLAB, 1985; TDB,  1985)
            Chemical  Formula
            Molecular Weight
            Physical  State  (25°C)
            Boiling Point
            Melting Point
            Vapor  Pressure  (20°C)
            Specific  Gravity
            Water  Solubility  (25°C)
            Log  Octanol/Water Partition
            Taste  Threshold
            Odor Threshold
            Conversion Factor
White crystalline solid

   35 to 36°C

   0.97 x 10-5 mm Hg

   55 to 60 mg/L
   3.11 (calculated)
           Methyl parathion has been found in  1,402 of 29,002 surface water
           samples analyzed and in 25 of 2,878 ground water samples  (STORET,
           1987).  Samples were collected at 3,676 surface water  locations and
           2,026 ground water locations, and methyl parathion was found in 22
           states.  The 85th percentile of all nonzero samples was 1.18 ug/L
           in  surface water and 1 ug/L in ground water sources.   The maximum
           concentration found was 13 ug/L in  surface water and 1.6 ug/L in
           ground water.

     Methyl  Parathion                                              August,  1987


     Environmental  Fate

          0  Methyl parathion  (99% pure) at 10 ppm was added  to  sea water  and
            exposed to sunlight; some samples were  also  kept in the dark  (controls).
            After  6 days,  57% of the parent compound had degraded but  the degradates
            were not  identified.  Since only 27% of the  parent  compound had degraded
            in  the dark controls, this indicates that methyl parathion is subject
            to  photodegradation in sea water (U.S.  EPA,  1981).

          0  The degradation rate of two formulations (EC and MCAP) of  methyl
            parathion, applied at 0.04 ppm, was compared in  a sediment/water
            system.   Degradates were not identified; however, the parent  compound
            had a  half-life of 1 to 3 days in water.  In the hydrosoil plus
            sediment, methyl  parathion applied as an emulsifiable concentrate
            formulation had a half-life of 1 to 3 days,  whereas for the micro-
            encapsulated  formulation, the half-life was  3  to 7  days (Agchem,  1983).

          0  Methyl parathion  was relatively immobile in  30-cm soil columns of  sandy
            loam,  silty clay  loam and silt loam soils leached with 15.7 inches of
            water, with no parent compound found below 10  cm or in the column
            leachate, which was the case for the column  of sand (Pennwalt Corporation,

          0  Methyl parathion  (MCAP or EC formulation) at 5 Ib ai/A (active
            ingredient/acre)  was detected in runoff water  from  field plots irrigated
            4 to 5 days posttreatment.  Levels found in  soil and turf  plots ranged
            from 0.13 to  21 ppm and 0.17 to 0.20 ppm, respectively (Pennwalt
            Corporation,  1972).

          0  A field dissipation study with methyl parathion  (4  Ib/gal  EC)  at  3 Ib
            ai/A,  applied  alone or in combinaton with Curacron,  dissipated to
            nondetectable  levels (<0.05 ppm) within 30 days  in  silt loam  and
            loamy  sand soils  (Ciba-Geigy Corporation, 1978).



          0  Braeckman et  al.  (1983) administered a  single  oral  dose of 35S-methyl
            parathion (20  mg/kg) by stomach tube to four mongrel dogs. Peak
            concentrations in plasma ranged from 0.13 to 0.96 ug/mL, with peak
            levels occurring  2 to 9 hours after dosing.  In  two dogs given single
            oral doses of  35s-methyl parathion (3 mg/kg) in  this study, absorption
            was estimated  to  be 77 and 79%, based on urinary excretion of label.
            The authors concluded that methyl parathion  was  well absorbed from
            the gastrointestinal tract.

          0  Hollingworth  et al. (1967) gave a single oral  dose  of 32P-labeled
            methyl parathion  by gavage (3 or 17 mg/kg, dissolved in olive oil) to
            male Swiss mice.  Recovery of label in  the urine reached a maximum of
            about  85%, most of this occurring within 18  hours of dosing.   The
            amount of label in the feces was low, never  exceeding 10%  of  the
            dose.  This indicated that absorption was at least  90% complete.

Methyl Parathion                                          August, 1987



     0  Ackermann and Engst (1970) administered methyl parathion to pregnant
        albino rats and examined the dams and fetuses for the distribution
        of the pesticide.   The pregnant rats (weighing about 270 g each) were
        given 3 mg (11.1  mg/kg) of methyl parathion orally on days 1 to 3 of
        gestation and sacrificed 30 minutes after the last dose.  Methyl
        parathion was detected in the maternal liver (25 ng/g), placenta
        (80 ng/g), and in fetal brain (35 ng/g), liver (40 ng/g) and back
        musculature (60 ng/g).


     0  Hollingworth et al. (1967) gave 32p_labeled methyl parathion by
        gavage (3 or 17 mg/kg, dissolved in olive oil) to male Swiss mice.
        About 85% of the label appeared in the urine within 72 hours.  Urinary
        metabolites identified -24 hours after the low dose were:  dimethyl
        phosphoric acid (53.1%); dimethyl phosphorothioic acid  (14.9%);
        desmethyl phosphate (14.1%); desmethyl phosphorothioate (11.7%);
        phosphoric acid (2eO%); methyl phosphoric acid (1.7%); and phosphate
        (0.6%).  The radioactivity in the urine was fully accounted for by
        hydrolysis products and P=0 activation products.  No evidence was
        found for reduction of the nitro group to an amine, oxidation of the
        ring methyl group, or hydroxylation of the ring.  A generally similar
        pattern was observed at the high dose, except for a lower percentage
        of dimethyl phosphoric acid (31.9%) and higher percentages of desmethyl
        phosphate (23.1%)  and desmethylphosphorothionate (18.8%).  Based on
        this, the authors proposed a metabolic scheme involving oxidative
        desulfuration, oxidative cleavage of the phospho group from the ring
        and hydrolysis of the phosphomethyl esters.

     0  Neal and DuBois (1965) investigated the in vitro detoxification of
        methyl parathion and other phosphorothioates using liver microsomes
        prepared from adult male Sprague-Dawley rats.  Metabolism was found
        to involve oxidative desulfuration followed by hydrolysis to yield
        p-nitrophenol.  Extracts from livers of adult male rats exhibited
        higher metabolic activity than that of adult females  (3.2 versus
        1.9 units, where one unit equals 1 ug p-nitrophenol/50 mg liver
        extract)  (p 
    Methyl  Parathion                                           August,  1987

            NADPH2.   The amounts of  phenol  and  oxygen analog  formed were 3.8 and
            3.7 uM in the  rabbit liver  extract  and 2.5 and  5.4 uM in the rat
            liver extract, respectively.
            Braeckman  et al.  (1983) administered  individual  doses  of 3 mg/kg of
            35s-methyl parathion  to two  mongrel dogs.   In  each  dog,  the agent was
            given once intravenously  and,  1  week  later,  once orally  via stomach
            tube.   This dosing pattern was repeated  once in  one dog.  Urine was
            collected  every  24 hours  for 6 days after  each'treatment.   Urinary
            excretion  6 days  after oral  dosing was 63% in  the animal without
            repeated dosing  and 70% and  78%  in the other.  Urinary excretion
            6 days after intravenous  dosing  was 80%  in the animal  without repeated
            dosing and 95  to  96%  in the  other.  Most of  the  label  appeared in urine
            within two days.  Other excretory routes were  not monitored.

            Hollingworth et  al. (1967) gave  32p-iabeled  methyl  parathion (3 or
            17 mg/kg,  dissolved in olive oil) by  gavage  to male Swiss mice.
            Recovery of label in  the  urine reached a maximum of about 85%, most
            of this occurring within  18  hours of  dosing.  The amount of label in
            the feces  was  low, never  exceeding 10% of  the  dose. This indicated
            that absorption  was at least 90% complete.
       Short-term  Exposure

         0   Nemec  et al.  (1968)  monitored  cholinesterase  (ChE)  levels in two
            workers  (entomologists) who  examined  plants in  a  cotton  field after
            it had been sprayed  with  an  ultra-low-volume  (nonaqueous) preparation
            of methyl parathion  (1.5  to  2  Ib/acre).   The  men  entered a cotton
            field  to examine  the plants  on 3  different days over  a 2-week period;
            two of these  occasions  were  within 2  hours after  the  ultra-low-volume
            spraying,  and the third occasion  was  24  hours after a spraying.
            After  each field  trip their  arms  were washed  with acetone and the
            adhering methyl parathion determined.   It was found that contact with
            the plants 2  hours after  spraying resulted in 2 to 10 ng of methyl
            parathion residue on the  arms;  exposure  24 hours  after spraying
            resulted in a residue on  the arms of  0.16 to  0.35 mg.  The amount of
            pesticide absorbed was not estimated.  No toxic symptoms were experienced
            by either man, but measurement of red blood cell  ChE  activity immediately
            after  the third of these  exposures showed a decrease  in  activity to
            60 to  65% of  preexposure  levels.   These  values  did not increase
            significantly over the next  24 hours.  It was concluded  that workers
            should not enter  such a field  until more than 24  hours,  and preferably
            48 hours,  have elapsed after spraying with ultra-low-volume insecticide
            sprays.   Water emulsion sprays  were not  tested, but the  authors
            cautioned that it cannot  be  assumed that they are less hazardous than
            the ultra-low-volume spray residues.

Methyl Parathion                                          August, 1987

     0  Rider et al. (1969,  1970,  1971) studied the toxicity of technical
        methyl parathion (purity not specified) in human volunteers.  Each
        phase of the study was done with different groups of seven male
        subjects, five of whom were test subjects and two were vehicle
        controls (Rider et al., 1969).  Each study phase was divided into a
        30-day pre-test period for establishing cholinesterase baselines, a
        30-day test period when a specific dose of methyl parathion was
        given, and a post-test period.

     e  Thirty-two different dosages were evaluated by Rider et al. (1969),
        ranging from 1 to 19 mg/day.  Early in the study, several of the
        groups were given more than one dose level during a single phase.
        The initial amount was 1.0 mg with an increase of 0.5 mg during each
        succeeding test period up to 15.0 mg/day.  At this point, the dose was
        increased by 1.0 mg/day to a total dose of 19.0 mg/day.  Pesticide in
        corn oil was given orally in capsules, once per day for each test
        period of 30 days.  At no time during any of the studies were there
        any significant changes in blood counts, urinalyses, or prothrombin
        times, or was there any evidence of toxic side effects.  Cholinesterase
        activity of the plasma and red blood cells (RBCs) was measured twice
        weekly prior to, during and after the dosing period.  The authors
        considered a mean depression of 20 to 25% or greater in ChE activity
        below control levels to be indicative of the toxic threshold.  At
        11.0 mg/day, a depression of 15% in plasma ChE occurred, but doses up
        to and including 19 mg/day did not produce any significant ChE

     0  Rider et al. (1970) studied the effects of 22, 24 and 26 mg/day
        technical methyl parathion.  There were no effects observed at
        22 mg/day.  At 24 mg/day, plasma and RBC ChE depression was
        produced in two subjects, the maximum decreases being 24 and 23% for
        plasma, and 27 and 55% for RBC.  The mean maximal decreases (in all
        five subjects) were 17% for plasma and 22% for RBC.  With 26 mg/day
        RBC ChE depression was again produced in only two of the subjects,
        with maximum decreases of 25 and 37%.  The mean maximum decrease was
        18%.  Plasma cholinesterase was not significantly altered.

      0  Rider et al.  (1971) assessed the effects of 28 and 30 mg/day technical
        methyl parathion.  At 28 mg/day, a significant decrease in RBC ChE
        was produced in three subjects  (data not given), with a maximum mean
        decrease of 19%.  With a dose of 30 mVday, a mean maximum depression
        of 37% occurred.  Based on their criteria of 20 to 25% average
        depression of ChE activity, the authors concluded that this was the
        level of minimal incipient toxicity.  Body weights of the test subjects
        were not reported, but assuming an average body weight of 70 kg, a
        dose of  22 mg/day corresponds to a No-Observed-Adverse-Effect-Level'
        (NOAEL) of 0.31 mg/kg/day, and  the 30 mg/day dose corresponds to 0.43
        mg/kg/day.  The NOAEL is considered to be 22 mg/day herein because of
        the apparent sensitivity of, some individual subjects at higher doses
        to have met the 20 to 25% criteria for ChE depression as an effect.

    Long-term Exposure

      0  No information was found in the available literature on the health
        effects of methyl parathion in humans.

Methyl Parathion                                          August, 1987



   Short-term Exposure

     0  Reported oral LD5Q values for methyl parathion include 14 and 24 rag/kg
        in male and female Sherman rats, respectively (Gaines, 1969); 14.5 and
        19.5 mg/kg in male and female CD-1  mice,  respectively (Haley et al.,
        1975);  30 mg/kg in male ddY mice (Isshiki et al., 1983);  18.0 and
        8.9 mg/kg in male and female Sprague-Dawley rats, respectively (Sabol,
        1985);  and 9.2 mg/kg in rats of unreported strain (Galal et al., 1977).

     0  Galal et al. (1977) determined the  subchronic median lethal dose
        (OLD5Q) of methyl parathion (purity not specified) in adult albino
        rats.  Groups of 10 animals received an initial daily oral dose (by
        gavage) of 0.37 mg/kg (4% of the acute oral LD^Q).  Every 4th day the
        dose was increased by a factor of 1.5 (dose based on the
        body weight of the animals as recorded at 4-day intervals).  Treatment
        was continued until death or termination at 36 days.  Hematological
        and blood chemistry analyses were performed initially and on the 21st
        and 36th days of the study.  Histopathological studies of the liver,
        kidneys and heart were also carried out on the 21st and 36th days of
        treatment.  The C-LD5Q obtained was 13 mg/kg.  The authors concluded
        that the most predominant hazards of subchronic exposure to methyl
        parathion were weight loss, hyperglycemia and macrocytic anemia, all
        probably secondary to hepatic toxicity.  Since an increasing dose
        protocol was used, this study does  not identify a NOAEL or a Lowest-
        Observed-Adverse-Effect-Level (LOAEL).

     0  Daly et al. (1979) administered methyl parathion  (technical, 93.65%
        active ingredient) to Charles River CD-1  mice for 4 weeks at levels
        of 0, 25 or 50 ppm in the diet.  Assuming that 1 ppm in the diet of
        mice corresponds to 0.15 mg/kg/day (Lehman, 1959), this is equivalent
        to doses of about 0, 3.75 or 7.5 mg/kg/day.  Five animals of each sex
        were used at each dose level.  Mean body weights were lower (p <0.05)
        than control for all treated animals throughout the test period.  Mean
        food consumption was lower (p <0.05) throughout for all test animals
        except females at the 25-ppm level.  Mortality, physical observations,
        and gross postmortem examinations did not reveal any treatment-related
        effects.  Cholinesterase measurements were not performed.  Based on
        body weight gain, the LOAEL for this study was identified as 25 ppm
        (3.75 mg/kg/day).

     0  Tegeris and Underwood (1977) examined the effects of feeding methyl
        parathion (94.32%.pure) to beagle dogs (4 to 6 months of age, weighing
        5 to 10 kg) for 14 days.  Two animals of each sex were given doses
        of 0, 2.5, 5 or 10 mg/kg/day.  All animals survived the 14-day test
        period.  Mean feed consumption and  weight gain were significantly
        (p <0.05) depressed for both sexes  at the 5 and 10 mg/kg/day dose
        levels.  After the 3rd day, animals in the high-dose group began
        vomiting after all meals.  Vomiting was observed sporadically at the
        lower dose levels, particularly during the 2nd week.  The authors
        attributed this to acetylcholinesterase inhibition, but no measure-
        ments were reported.  No other symptomatology was described.  Based

Methyl Parathion                                          August, 1987


        on weight loss and vomiting, this study identified a LOAEL of
        2.5 ing/kg/day in the dog.

     0  Fan et al. (1978) investigated the immunosuppressive effects of methyl
        parathion administered orally to Swiss (ICR) mice.  The pesticide
        (purity not specified) was fed in the diet at dose levels corresponding
        to 0, 0.08, 0.7 or 3.0 mg/kg/day for 4 weeks.  Active immunity was
        induced by weekly injection of vaccine (acetone-killed Salmonella
        typhimurium) during the period of diet treatment.  Defense against
        microbial infection was tested by intraperitoneal injection of a
        single LD^g dose of active S_. typhimurium cells.  Protection by
        immunization was stated to be decreased in methyl parathion-treated
        animals, but no dose-response data were provided.  The authors stated
        that pesticide treatment extending beyond 2 weeks was required to
        obtain significant increases in mortality.  Increased mortality was
        associated with an increased number of viable bacteria in blood,
        decreased total gamma-globulins and specific immunoglobins in serum,
        and reduced splenic blast transformation in response to mitogens.

      8  Shtenberg and Dzhunusova (1968) studied the effect of oral exposure to
        methyl parathion (purity not specified) on immunity in albino rats
        vaccinated with NIISI polyvaccine.  Three tests  (six animals each)
        were conducted in which:  (a) the vaccination was done after the
        animals had been on a diet supplying 1.25 mg/kg/day metaphos (methyl
        parathion) for 2 weeks;  (b) the diet and vaccinations were initiated
        simultaneously; and (c) the diet was initiated 2 weeks after vaccina~
        tion.  The titer of agglutins in immunized control rats was 1:1,200.
        This titer was decreased in all exposed groups as follows:  1:46 in
        series  (a), 1:75 in series  (b) and 1:33.3 in series (c).  The authors
        judged  this to be clear evidence of inhibition of immunobiological
        reactivity in the exposed animals.  Changes in blood protein fractions
        and in  serum concentration of albumins were not  statistically significant.
        Based on immune suppression, a LOAEL of 1.25 mg/kg/day was identified.

    Dermal/Ocular Effects

      0  Gaines  (1969) reported  a dermal LD5Q of 67 mg/kg  for methyl parathion
        in male and female Sherman rats.

      0  Galloway  (1984a,b) studied  the skin and eye irritation properties of
        methvl  parathion (technical; purity not specified) using albino New
        Zealand White rabbits.   In  the skin irritation  test, 0.5 mL undiluted
        pesticide was applied and the treated area occluded for 4 hours.
        This treatment resulted  in dermal edema that persisted for 24 hours,
        and in  erythema that lasted for 6 days.  After a  total observation
        period  of 9 days, a score of 2.0 was derived, and technical methyl '
        parathion was rated as  a weak irritant.   In the  eye irritation test,
        0.1 mL  of the undiluted pesticide was applied to  nine eyes.  Three
        were washed after exposure, and six were left unwashed.  Conjunctival
        irritation was observed starting at 1 hour and lasting up to 48 hours
        postexposure.  Maximum  average irritation scores  of 11 and 10.7 were
        assigned  for nonwashed  and washed eyes, respectively, and technical
        methyl  parathion was considered a weak irritant.

Methyl Parathion                                          August, 1987
     0  Galloway (1985) used guinea pigs to examine the sensitizing potential
        of methyl parathion (technical;  purity not stated).  Ten doses of
        0.5 mL of a 10% solution (w/v in methanol) were applied to the clipped
        intact skin of 10 male guinea pigs (albino Hartley strain) over a
        36-day period.  This corresponds to an average dose of 13.9 mg/kg/day.
        Another group was treated with 2,4-dinitrochlorobenzene as a positive
        control.  No skin sensitization  reaction was observed in methyl
        parathion-treated animals.

     0  Skinner and Kilgore (1982) studied the acute dermal toxicity of methyl
        parathion in male Swiss-Webster  mice,  and simultaneously determined
        ED50 values for cholinesterase and acetylcholinesterase inhibition.
        Methyl parathion (analytical grade, 99% pure) was administered in
        acetone solution to the hind feet of the mice; the animals were
        muzzled to prevent oral ingestion through grooming.  The derma'l LDsg
        was 1,200 mg/kg.  The ED50 was 950 mg/kg for cholinesterase inhibition
        and 550 mg/kg for acetylcholinesterase inhibition.

   Long-term Exposure

     0  Daly and Rinehart (1980) conducted a 90-day feeding study of methyl
        parathion (93.65% pure) using Charles  River CD-1  mice.  Groups of 15
        mice of each sex were given diets containing the pesticide at levels
        of 0, 10, 30 or 60 ppm.  Assuming that 1 ppm in the diet of mice corre-
        sponds to 0.15 mg/kg/day (Lehman, 1959), this is equivalent to doses
        of about 0,  1.5, 4.5 or 9.0 mg/kg/day.  All mice survived the test.
        Mean body weights were significantly (p <0.05) depressed for both
        sexes at 60 ppm throughout the study and for males during the first
        5 weeks at 30 ppm.  Animals of both sexes had a slight but not
        significant (p >0.05) increase in the  mean absolute and relative
        brain weights at 60 ppm.  There  were dose-related decreases (p <0.05)
        in the mean absolute and relative testes weights of all treated
        males and in the ovary weights of the  females at 30 and 60 ppm.
        Gross and microscopic examination revealed no dose-related effects.
        Histological examination revealed no findings in the brain, testes or
        ovary to account for the observed changes in the weights of these
        organs.  Measurements on ChE were not  performed.   Based on decreased
        testes weight, the LOAEL for this study was 10 ppm (1.5 mg/kg/day).

     0  Tegeris and Underwood (1978) investigated the toxicity of methyl
        parathion (94.32% active ingredient) in beagle dogs fed the pesticide
        for 90 days at dose levels of 0, 0.3,  1.0 or 3.0 mg/kg/day.  Four dogs
        (4-months old, 4.5 to 8.0 kg) of both  sexes were used at each dose
        level.  Soft stools were observed in all treatment groups throughout,
        and there was also occasional spontaneous vomiting.  There were no
        persistent significant (p >0.05) effects on body weight gain,  feed
        intake, fasting blood sugar, BUN, SGPT, SGOT, hematological, or
        urological indices.  Organ weights were within normal limits,  with
        the exception of pituitary weights of  females at 3.0 mg/kg, which
        were significantly (p <0.05) higher than the control values.  Gross
        and microscopic examination revealed no compound-related abnormalities.
        Plasma ChE was significantly (p  <0.05) depressed  in both sexes at 6
        and 13 weeks at 3 mg/kg/day, and in the males only at 1.0 mg/kg/day

Methyl Parathion                                          August, 1987

                                     -1 fl-
        at 13 weeks;  erythrocyte ChE was also significantly (p <0.05) depressed
        in all animals at 6 and 13 weeks at 3 mg/kg/day, and in both sexes at
        13 weeks at 1.0 mg/kg/day; brain ChE was significantly (p <0.05)
        depressed in  both sexes at 3.0 mg/kg/day.  Based on ChE depression,
        the NOAEL and LOAEL for this study were identified as 0.3 mg/kg/day
        and 1.0 mg/kg/day, respectively.

     0  Ahmed et al.  (1981) conducted a 1-year feeding study in beagle dogs.
        Methyl parathion (93.6% pure) was administered in the diet at ingested
        dose levels of 0, 0.03, 0.1 or 0.3 mg/kg/day.  Eight animals of each
        sex were included at each dose level, with no overt signs of toxicity
        noted at any  dose.  There were no treatment-related changes in food
        consumption or body weight.  Cholinesterase determinations in plasma,
        red blood cells and brain revealed marginal variations, but the
        changes were  not consistent and were judged by the authors to be
        unrelated to  dosing.  Organ weight determinations showed changes in
        both males and females at 0.1 and 0.3 mg/kg/day, but the changes were
        neither dose-related nor consistent.  It was concluded that there was
        no demonstrable toxicity of methyl parathion fed to the dogs at these
        levels.  The  NOAEL for this study was 0.3 mg/kg/day.

     0  NCI (1978) conducted a 2-year feeding study of methyl parathion
        (purity not specified) in F344 rats (50/sex/dose) at dose levels of
        0, 20 or 40 ppm in the diet.  Assuming that 1 ppm in the diet of rats
        corresponds to 0.05 mg/kg/day (Lehman, 1959), this is equivalent to
        dose levels of about 0, 1 or 2 mg/kg/day.  Cholinesterase levels were
        not measured, but no remarkable clinical signs were noted, and no
        significant (p <0.05) changes were observed in mortality, body weight,
        gross pathology or histopathology.  Based on this, a NOAEL of 40 ppm
        (2 mg/kg/day) was identified in rats.

     0  NCI (1978) conducted a chronic  (105-week) feeding study in B6C3Fi
        mice (50/sex/dose).  Animals were initially fed methyl parathion
        (94.6% pure)  at dose levels of 62.5 or 125 ppm.  Assuming that 1 ppm
        in the diet of mice corresponds to 0.15 mg/kg/day (Lehman, 1959),
        this is equivalent to doses of about 9.4 or 18.8 mg/kg/day.  Because
        of severely depressed body weight gain in males, their doses were
        reduced at 37 weeks to 20 or 50 ppm, and the time-weighted averages
        were calculated to be 35 or 77 ppm.  This corresponds to doses of
        about  5.2 or  11.5 mg/kg/day, respectively.  Females were fed at the
        original levels throughout.  Mortality was significantly (p  <0.05)
        increased only in female mice at 125 ppm.  Body weights were lower
        (p <0.05) for both sexes throughout the test period and decreases
        were dose-related.  No gross or histopathologic changes were noted,
        and ChE activity was not measured.  Based on body weight, this study
        identified a LOAEL of 35 ppm (5.2 mg/kg/day) in male mice.

     0  Daly et al.  (1984) conducted a chronic feeding study of methyl
        parathion (93.65% active ingredient) in Sprague-Dawley (CD) rats
        (60/sex/dose) at dose levels of 0, 0.5, 5 or 50 ppm in the diet.
        Using  food intake/body weight data given in the study report, these
        levels approximate doses of about 0, 0.025, 0.25 or 2.5 mg/kg/day.
        At 24  months, five animals of each sex were sacrificed for qualitative

Methyl Parathion                                          August,  1987

                                     -1 1-
        and quantitative tests for neurotoxicity.  Ophthalmoscopic examinations
        were conducted on females  at 3,  12 and 24 months and terminally.
        Hematology, urinalysis and clinical chemistry analyses were performed
        at 6, 12, 18 and 24 months.  Mean body weights were reduced (p <0.05)
        throughout the study for both sexes at 50 ppm.  At this dose level,
        food consumption was elevated (p <0.05) for males during weeks 2
        to 13, but reduced for females for most of the study.  Hemoglobin,
        hematocrit and RBC count were significantly (p <0.05) reduced for
        females at 50 ppm at 6,  12, 18 and 24 months.  For males at 5 and
        50 ppm at 24 months, hematocrit and RBC count were significantly
        (p <0.05) reduced and hemoglobin was reduced, but not significantly
        (p >0.05).  At 50 ppm,  plasma and erythrocyte ChE were significantly
        (p <0.05) depressed for both sexes during the test, and brain ChE was
        significantly (p <0.05)  decreased at termination.  Slight decreases
        in ChE activity were also  observed in animals at 5 ppm, but these
        changes were not statistically significant (p >0.05).  For males, the
        absolute weight and the ratio to brain weight of the testes, kidneys
        and the liver were reduced by 10 to 16% (not significant, p >0.05)  in
        both the 5- and 50-ppm groups, while for females absolute and organ/body
        weights for the brain and  heart (also heart/brain weight) were found
        to be elevated significantly (p <0.05) at the same dose levels.   Overt
        signs of cholinergic toxicity (such as alopecia, abnormal gait and
        tremors) were observed in  the 50-ppm animals and in one female at
        5 ppm.  At 24 months, 15 females were observed to have retinal degen-
        eration.  There was also a dose-related occurrence of retinal posterior
        subcapsular cataracts,  possibly related or secondary to the retinal
        degeneration, since 5 of the 10 cataracts occurred in rats with retinal
        atrophy.  The incidence of retinal atrophy was 20/55 at 50 ppm,  1/60 at
        5 ppm, 3/60 at 0.5 ppm and 3/59 in the control group.  Examination of
        the sciatic nerve and other nervous tissue from five rats per sex
        killed at week 106 gave evidence of peripheral neuropathy (abnormal
        fibers, myelin corrugation, myelin ovoids) in both sexes at 50 ppm
        (p <0.05).  Too few fibers were examined at the lower doses to perform
        statistical analyses, but  the authors stated that nerves from both
        sexes in low- and mid-dose groups could not be distinguished qualita-
        tively from controls.  Slightly greater severity of nerve changes
        found in two males was not clearly related to treatment.  No other
        lesions were observed that appeared to be related to ingestion of
        methyl parathion.  Based on hematology, body weight, organ weights,
        clinical chemistry, retinal degeneration and cholinergic signs,  a
        NOAEL of 0.5 ppm (0.025 mg/kg/day) was identified in this study,

   Reproductive Effects

     0  Lobdel and Johnston (1964) conducted a three-generation study in
        Charles River rats.  Each  parental dose group included 10 males  and
        20 females.  The investigators incorporated methyl parathion (99% pure)
        in the diet of males and females at dpse levels of 0, 10 or 30 ppm,
        except for reduction of  each dose by 50% during the initial 3 weeks
        of treatment, to produce dose equivalents of 0, 1.0 and 3.0 mg/kg/day,
        respectively.  There was no pattern with respect to stillbirths,
        although the 30-ppm groups had a higher total number of stillborn.
        Survival was reduced in weanlings of the Fia,  Flb and F2a groups at

Methyl Parathion                                          August, 1987
        30 ppm, and in weanlings of the f^a 9roup at 10 ppm.  At 30 ppm,
        there was also a reduction in fertility of the ?2b dams at the second
        mating; the first mating resulted in 100% of the animals having
        litters, while at the second mating, only 41% had litters.  Animals
        exposed to 10 ppm methyl parathion did not demonstrate significant
        deviations from the controls.   A NOAEL of 10 ppm (t.O mg/kg/day) was
        identified in this study.

     0  Daly and Hogan (1982) conducted a two-generation study of methyl
        parathion (93.65% pure) toxicity in Sprague-Dawley rats.  Each parental
        dose group consisted of 15 males and 30 females.  The compound was
        added to the diet at levels of 0, 0.5, 5.0 or 25 ppm.  Using compound
        intake data from the study report, equivalent dose levels are about
        0, 0.05, 0.5 or 2.5 mg/kg/day.  Feeding of the diet was initiated
        14 weeks prior to the first mating and then continued for the remainder
        of the study.  Reduced body weight (p <0.05) was observed in FQ and
        PI dams at the 25-ppm dose level.  A slight decrease in body weight
        was noted in F^a and F2a pups in the 25-ppm group, but this was not
        significant (p >0.05).  Overall, the authors concluded that there was
        no significant (p >0.05) effect attributable to methyl parathion in
        the diet.  Based on maternal weight gain, the NOAEL for this study
        was 5.0 ppm (0.5 mg/kg/day).

   Developmental Effects

     0  Gupta et al. (1985) dosed pregnant Wistar-Furth rats (10 to 12 weeks
        of age) with methyl parathion (purity not specified) on days 6 to 20
        of gestation.  Two doses were used:  1.0 mg/kg (fed in peanut butter)
        or 1.5 mg/kg (administered by gavage in peanut oil).  The low dose
        produced no effects on maternal weight gain, caused no visible signs
        of cholinergic toxicity and did not result in increased fetal resorp-
        tions.  The high dose caused a slight but significant (p <0.05)
        reduction in maternal weight gain (11% in exposed versus 16% in
        controls, by day 15) and an increase in late resorptions (25% versus
        0%).  The high dose also resulted in cholinergic signs (muscle fasicu-
        lation and tremors) in some dams.  Acetylcholesterase (AChE) activity,
        choline acetyltransferase (CAT) activity, and quinuclidinyl benzilate
        (QNB) binding to muscarinic receptors were determined in several
        brain regions of fetuses at 1, 7, 14, 21 and 28 days postnatal age,
        and in maternal brain at day 19 of gestation.  Exposure to 1.5 mg/kg
        reduced  (p <0.05) the AChE and increased CAT activity in all fetal
        brain regions at each developmental period and in the maternal brain.
        Exposure to 1.0 mg/kg caused a significant (p <0.05) but smaller and
        less persistent reduction of AChE activity in offspring, but no change
        in brain CAT activity.  Both doses reduced QNB binding in maternal
        frontal cortex (p <0.05), but did not alter the postnatal pattern of
        binding in fetuses.  In parallel studies, effects on behavior (cage
        emergence, accommodated locomotor activity, operant behavior) were
        observed to be impaired in rats exposed prenatally to 1.0 mg/kg, but
        not to  the 1.5-mg/kg dose.  No morphological changes were observed in
        hippocampus or cerebellum.  It was concluded that subchronic prenatal
        exposure to methyl parathion altered postnatal development of
        cholinergic neurons and caused subtle alterations in selected

Methyl Parathion                                          August, 1987

        behaviors of the offspring.   The fetotoxic LOAEL for this study was
        1.0 rag/kg.

     0  Gupta et al. (1984)  administered oral doses of 1.0 or 1.5 mg/kg/day
        of methyl parathion  (purity  not specified) to female Wistar-Furth rats
        on days 6 through 15 or on days 6 through 19 of gestation.  Protein
        synthesis in brain and other tissues was measured on day 15 or day 19
        by subcutaneous injection of radioactive valine.  The specific activity
        of this valine in the free amino acid pool and protein-bound pool
        (measured 0.5, 1.0 and 2.0 hours after injection) was significantly
        (p <0.05) reduced in various regions of the maternal brain and in
        maternal viscera, placenta and whole embryos (day 15),  and in fetal
        brain and viscera (day 19).   The inhibitory effect of methyl parathion
        on protein synthesis was dose dependent, greater on day 19 than on
        day 15 of gestation  and more pronounced in fetal than in maternal
        tissues.  With respect to protein synthesis in both maternal and
        fetal tissues, the LOAEL of  this study was 1.0 mg/kg.


     0  Van Bao et al. (1974) examined the lymphocytes from 31  patients exposed
        to various organophosphate pesticides for indications of chromosome
        aberrations.  Five of the examined patients had been exposed to methyl
        parathion.  Blood samples were taken 3 to 6 days after  exposure and
        again at 30 and 180  days. A temporary, but significant (p <0.05)
        increase was found in the frequency of chromatid breaks and stable
        chromosome-type aberrations  in acutely intoxicated persons.  Two of
        the methyl parathion-exposed persons were in this category, having
        taken large doses orally in  suicide attempts.  The authors concluded
        that the results of  this study strongly suggest that the organic
        phosphoric acid esters exert direct mutagenic effects on chromosomes.

     0  Shigaeva and Savitskaya (1981) reported that metophos (methyl para-
        thion) induced visible morphological mutations and biochemical mutations
        in Pseudomonas aeruginosa at concentrations between 100 and 1,000 ug/mL,
        and significantly (p <0.05)  increased the reversion rate in Salmonella
        typhimurium at concentrations between 5 and 500 ug/mL.

     0  Grover and Malhi (1985) examined the induction of micronuclei in bone
        marrow cells of Wistar male  rats that had been injected with methyl
        parathion at doses between one-third and one-twelfth of the LD5Q.
        The increase in micronuclei  formation led the authors to conclude
        that methyl parathion has high mutagenic potential.

     0  Mohn (1973) concluded that methyl parathion was a probable mutagen,
        based on the ability to induce 5-methyltryptophan resistance in
        Escherichia coli. Similar results were obtained using  the streptomycin-
        resistant system of  j:. coli  and the trp-conversion system of Saccharo-
        myces cerevisiae.

     0  Rashid and Mumma (1984) found methyl parathion to be mutagenic to S.
        typhimurium strain TA100 after activation with rat liver microsomal
        and cytosolic enzymes.

  Methyl Parathion                                          August, 1987

       0  Chen et al. (1981) investigated sister-chromatid exchanges (SCE) and
          cell-cycle delay in Chinese hamster cells (line V79) and two human
          cell lines (Burkitt lymphoma B35M and normal human lymphoid cell
          Jeff), and found methyl parathion to be the most active pesticide
          of eight tested with respect to its induction potential.

       8  Riccio et al. (1981) found methyl parathion to be negative in two
          yeast assay systems (diploid strains D3 and D7 of Saccharomyces
          cerevisiae), based on mitotic recombination (in D3), and mitotic
          crossing over, mitotic gene conversion, and reverse mutation (in D7)»

     Carcinogenici ty

       0  NCI (1978) conducted chronic (105-week) feeding studies of methyl
          parathion in F344 rats and B6C3F1 mice (50/sex/dose).  Rats were fed
          methyl parathion  (94.6% pure) at dose levels of 0, 20 or 40 ppm
          (equivalent to doses of 0, 1 or 2 mg/kg/day).  Mice were initially
          fed dose levels of 62.5 or 125 ppm, but because of severely depressed
          body weight gain  in males, their doses were reduced at 37 weeks to
          20 or 50 ppm, respectively.  Time-weighted averages for males were
          calculated to be  35 or 77 ppm (about 5.2 or 11.5 mg/kg/day).  Females
          received the original dose level throughout.  Based on gross and
          histological  examinations, no tumors were observed to occur at an
          incidence significantly higher than that of the control value in either
          the mice or rats.  The authors concluded that methyl parathion was
          not carcinogenic  in either species under the conditions of the test.

        0  Daly  et al.  (1984) fed Sprague-Dawley rats (60/sex/dose) methyl
          parathion  (93.65%) in the diet for 2 years.  Doses tested were 0,
          0.5,  5 or  50 ppm, estimated as equivalent to doses of 0, 0.025, 0.25
          or 2.5 mg/kg/day.  There were no significant (p >0.05) increases in
          neoplastic  lesions between treated and control groups.


        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)
           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).

Methyl Parathion                                          August, 1987

                    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 data were located in the available literature that were suitable for
deriving a One-day HA value.  It is recommended that the Ten-day HA value for
the 10-kg child (0.31 mg/L calculated below) be used at this time as a
conservative estimate of the One-day HA value.

Ten-day Health Advisory

     The studies by Rider (1969, 1970, 1971) have been selected to serve as
the basis for calculation of the Ten-day HA for methyl parathion.  In these
studies, human volunteers ingested methyl parathion for 30 days at doses
ranging from 1 to 30 mg/day.  The most sensitive indicator of effects was
inhibition of plasma ChE.  No effects in any subject were observed at a dose
of 22 mg/day (about 0.31 mg/kg/day with assumed 70-kg body weight), and this
was identified as the NOAEL.  Doses of 24 mg/day inhibited ChE activity in
plasma and red blood cells in two of five subjects, maximum decreases being
23 and 24% in plasma and 27 and 55% in red blood cells.  Higher doses (26 to
30 mg/day) caused greater inhibition.  On this basis, 24 mg/day (0.34 mg/kg/day)
was identified as the LOAEL.  Short-term toxicity or teratogenicity studies
in animals identified LOAEL values of 1.0 to 2.5 mg/kg/day (Gupta et al.,
1984, 1985; Shtenberg and Dzhunusova, 1968; Tegeris and Underwood, 1977), but
did not identify a NOAEL value.

     Using a NOAEL of 0.31 mg/kg/day, the Ten-day HA for a 10-kg child is
calculated as follows:

        Ten-day HA = (0-31 mg/kg/day) (10 kg) = 0.31 mg/L (310.0 ug/L)
                         (10)  (1 L/day)


        0.31 mg/kg/day = NOAEL, based on absence of toxic effects or inhibition
                         of ChE in humans exposed orally for 30 days.

                 10 kg = assumed body weight of a child.

                    10 = uncertainty factor, chosen in accordance with NAS/ODW
                         guidelines for  use with a  NOAEL from a study in humans.

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

Longer-term Health Advisory

     The 90-day feeding study in dogs by Tegeris and Underwood (1978) has
been selected to serve as the basis for  calculation of the Longer-term HA
for methyl parathion.  In this study, a  NOAEL of 0.3 mg/kg/day was identified.

Methyl Parathion                                          August,  1987

based on absence of effects on body weight, food consumption,  clinical chem-
istry, hematology,  urinalysis, organ weights, gross pathology, histopathology
and ChE activity.  Itie LOAEL,  based on ChE inhibition,  was 1.0 mg/kg/day.
These values are supported by  the results of Ahmed et al. (1981),  who
identified a NOAEL of 0.3 mg/kg/day in a 1-year feeding study  in dogs, and
by the study of Daly and Rinehart (1980), which identified a LOAEL of
1.5 mg/kg/day (based on decreased testes weight) in a 90-day feeding study in

     Using a NOAEL, of 0.3 mg/kg/day, the Longer-term HA for a  10-kg child is
calculated as follows:

        Longer-term HA = (0.3  mg/kg/day) (10 kg) = 0.03 mg/L (30 ug/L)
                             (100)  (1 L/day)


        0.3 mg/kg/day = NOAEL, based on absence of effects on  body weight,
                        food consumption, clinical chemistry,  hematology,
                        urinalysis, organ weights, gross pathology, histo-
                        pathology and ChE activity in dogs fed methyl parathion
                        for 90 days.

                10 kg = assumed body weight of a child.               ^

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

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

      Using  a NOAEL of 0.3 mg/kg/day, the Longer-term HA for a 70-kg adult is
calculated  as follows:

        Longer-term  HA =  (0.3 mg/kg/day)  (70 kg)  , 0.i0 mg/L  (100 ug/L)
                              (100)  (2 L/day)
         0.3 mg/kg/day = NOAEL, based on absence of effects on body weight,
                        food consumption, clinical chemistry, hematology,
                        urinalysis, organ weights, gross pathology, histo-
                        pathology and ChE activity in dogs fed methyl parathion
                        for 90 days.

                 70  kg = assumed body weight  of an adult.

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

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

Methyl Parathion                              ,           August, 1987


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

     The 2-year feeding study in rats by Daly et al. (1984) has been selected
to serve as the basis for calculation of the Lifetime HA for methyl parathion.
In this study, a NOAEL of 0.025 mg/kg/day was identified, based on the absence
of effects on body weight, organ weights, hematology, clinical chemistry, retinal
degeneration and cholinergic signs.   A LOAEL of 0.25 mg/kg/day was identified,
based on decreased hemoglobin, red blood cell counts, and hematocrit (males),
changes in organ-to-body weight ratios (males and females) and one case of
visible cholinergic signs.  There was increased retinal degeneration at
2.5 mg/kg/day, but this was not greater than control at 0.25 or 0.025 mg/kg/day.
This LOAEL value (0.25 mg/kg/day) is lower than most other NOAEL or LOAEL
values reported in other reports. For example, NOAEL values of 0.3 to 3.0
mg/kg/day have been reported in chronic studies by Ahmed et al. (1981), NCI
(1978), Lobdell and Johnston (1964)  and Daly and Hogan (1982).

     Using a NOAEL of 0.025 mg/kg/day, the Lifetime HA for a 70-kg adult is
calculated as follows:

Step 1:  Determination of the Reference Dose (RfD)

                 RfD = (0.025 mq/kg/day) = Q.00025 mg/kg/day


        0.025 mg/kg/day = NOAEL,  based on absence of cholinergic signs or
                          other adverse effects in rats exposed to methyl ,
                          parathion  in the diet for 2 years.

   Methyl Parathion                  t                        August,  1987

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

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

              DWEL =  (0.00025 mg/kg/day) (70 kg) . 0.009   /L  (9   /L)
                              (2 L/day)


            0.00025 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 = (0.009 mg/L) (20%) = 0.002 mg/L (2 ug/L)


            0.009 mg/L = DWEL.

                  20% = relative source contribution from water.

   Evaluation of Carcinogenic Potential

         0   No evidence of  carcinogenic activity was detected in either rats or
            mice in a  105-week feeding study (NCI, 1978).

         0   Statistically significant (p <0.05) increases in neoplasm  frequency
            were not found  in a 2-year feeding study in rats (Daly et  al.,  1984).

         0   The  International Agency  for Research on Cancer (IARC) has not
            evaluated  the carcinogenicity of methyl parathion.

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


         0   NAS  (1977) concluded that data were inadequate for  calculation  of  an
            ADI  for methyl  parathion.  However, using data on parathion,  NAS
            calculated an ADI for both parathion and methyl parathion  of  0.0043
            n"3A9/day, using, a NOAEL  of 0.043 mg/kg/day in humans (Rider  et al.,
            1969) and  an uncertainty  factor of 10  (NAS, 1977).  From this ADI,
            NAS  calculated  a chronic  Suggested-No-Adverse—Response Level  (SNARL)
            of 0.03 mg/L, based on  water consumption of 2 L/day by a 70-kg  adult,
            and  assuming a  20% RSC.

      Methyl Parathion                                          August,  1987

              The U.S.  EPA Office  of  Pesticide  Program  (EPA/OPP)  previously calcu-
              lated  a provisional  ADI (PADI) of 0.0015  mg/kg/day,  based  on a NOAEL
              of 0.3 mg/kg/day.  This is  based  on  the 90-day dog  study by Tegeris
              and Underwood (1978) and  a  200-fold  uncertainty  factor.  This PADI
              has been updated  to  use a value of 0.0025 mg/kg/day  based  on a NOAEL
              of 0.0250 mg/kg/day  in  a  2-year rat  chronic  feeding  study  and a
              100-fold  uncertainty factor.

              ACGIH  (1984)  has  proposed a time-weighted average threshold limit
              value  of  0.2 mg/m3.

              The National Institute  for  Occupational Safety and  Health  has recom-
              mended a standard for methyl parathion in air of 0.2 mg/ra3 (TDB,  1985).

              The U.S.  EPA has  established residue tolerances  for  parathion -and
              methyl parathion  in  or  on raw  agricultural commodities  that range
              from 0.1  to 0.5 ppm  (CFR, 1985).   A  tolerance is a  derived value
              based  on residue  levels,  toxicity data, food consumption levels,
              hazard evaluation and scientific  judgment; it is the legal maximum
              concentration of  a pesticide in or on a raw agricultural commodity or
              other  human or animal food  (Paynter  et al., undated).

              The World Health  Organization  established an ADI of  0.02 mg/kg/day
              (Vettorazi  and van den  Hurk, 1985).
              Analysis of  methyl parathion  is by  a  gas  chromatographic  (GC)  method
              applicable  to  the determination of  certain nitrogen-phosphorus
              containing  pesticides  in water samples  (U.S.  EPA,  1986b).   In  this
              method,  approximately  1 liter of sample is extracted  with  methylene
              chloride.   The extract is  concentrated  and the  compounds are separate.3
              using  capillary column LGC.   Measurement  is made using  a nitrogen-
              phosphorus  detector.   The  method detection limit has  not been  determined
              for  methyl  parathion,  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.
              Available data  indicate  that granular-activated  carbon  (GAC) and
              reverse  osmosis (RO) will effectively remove methyl parathion  from

              Whittaker (1980) experimentally determined  adsorption isotherms for
              methyl parathion and methyl parathion diazinion bi-solute solutions.
              As  expected,  the bi-solute solution  showed  a lesser overall carbon
              capacity than that achieved by the application of pure  solute  solution.

              Under laboratory conditions, GAC removed 99+%. of methyl parathion
              (Whittaker et al., 1982).

    Methyl Parathion                                           August, 1987



    ACGIH.  1984.   American Conference of Governmental Industrial Hygienists, Inc.
         Documentation of the threshold limit values for substances in workroom
         air,  3rd  ed.  Cincinnati,  OH:   ACGIH.

    Ackermann, H.,  and R. Engst.   1970.  The presence of organophosphorus
         insecticides  in the fetus.   Arch.  Toxikol.  26(1):17-22.  (In German)

    Agchem.*  1983.   Persistence  and release rate of Penncap M insecticide in
         water and  hydrosoil:  Project No.  WT-5-82.  Unpublished study.

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Methyl Parathion                                              August,  1987

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