820K88128                                              August' 1987
                                                              DRAFT
                MCPA
(4-Chloro-2-Methylphenoxy)-Acetic Acid

           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 ^hat
   any one of these models is able to predict risk more accurately than another.
   Because each model is based on differing  assumptions, the estimates that are
   derived can differ by several orders  of magnitude.

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    MCPA                                                        August,  1987

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II. GENERAL INFORMATION AND PROPERTIES

    CAS Mo.   94-74-6

    Structural Formula
                                          OCH2COOH
                        (4-Chloro-2-methyl phenoxy) -acetic acid

    Synonyms

         0  MCPA;  MCP;  Agroxone;  Hormotuho;  Metaxon.

    Uses

         0  MCPA is a hormone-type herbicide used to  control annual and perennial
            weeds  in cereals,  grassland and  turf (Hayes,  1982).

    Properties  (CHEMLAB,  1985; Meister,  1983)

            Chemical Formula                CgHgC^Cl
            Molecular Weight                200.63
            Physical State (25°C)            Light brown solid
            Boiling Point
            Melting Point                   118 to 119°C
            Vapor  Pressure (25°C)
            Density (25°C)                  1.56
            Water  Solubility                825 mg/L  (room temperature)
            Log Octanol/Water  Partition     2.07 (calculated)
              Coefficient
            Taste  Threshold
            Odor Threshold
            Conversion  Factor

    Occurrence

         0  MCPA has been found  in 4 of 12 surface water samples analyzed and in
            none of 99  ground  water samples  (STORET,  1987).  Samples were collected
            at 8 surface water locations and 97 ground water locations.  MCPA was
            found only  in California.  The 85th parcentile of all nonzero samples
            was 0.54 ug/L in surface water,  and the maximum concentration found
            was 0.54 ug/L.

    Environmental Fate

         0  MCPA is not hydrolyzed at pH 7 and 34 to  35°C (Soderquist and Crosby,
            1974,  1975).  MCPA in aqueous  solution (pH 8.3) has  a photolytic
            half-life of 20 to 24 days  in  sunlight.  With fluorescent light, MCPA

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        in aqueous  solution (pH 9.8)  produced three minor (less than 10%)
        photolysis  products:   4-chloro-2-methyl-phenol,  4-chloro-2-formylphenol
        and ^-cresol  in 71 hours (Soderquist and Crosby,  1974,  1975).

        MCPA  is  degraded more rapidly (1 day) in soils containing less than
        10% organic matter than in soil containing higher levels (3 to 9 days)
        (Torstensson,  1975).   This may be due to adsorption to  the  soil
        organic  matter.  MCPA, when applied a second time to soil,  is degraded
        twice as fast (6 to 12 days)  as it is after one application (15 to 28
        days).   Persistence does not depend greatly upon the soil type (Loos
        et al.,  1979).

        Unlabeled MCPA in rice paddy water under dark conditions is totally
        degraded by aquatic microorganisms in 13 days (Soderquist and Crosby,
        1974, 1975).

        MCPA  would  be expected to leach readily in most soils.   Phytotoxic
        levels of MCPA leached 30 cm in a sandy soil column eluted  with 50 cm
        of water (Herzel and Schmidt, 1979).  Using soil thin-layer chromato-
        graphic  techniques, MCPA was mobile (Rf 0.6 to 1.0) in  calcium
        montmorillonite clay (Helling, 1971) and in sandy loam, silt loam,
        and silty clay loam soils (Helling and Turner, 1968).  Mobility
        increases as  organic matter content decreases, possibly due to
        adsorption  of MCPA to this soil component.

        MCPA  does not volatilize from aqueous solution (pH 7.0) heated for
        13 days  at  34 to 35°C (Soderquist and Crosby, 1974, 1975).

        Using bioassays, MCPA appears to dissipate fairly rapidly (3 to 7
        weeks) from soil treated with levels of 0.75 to 1.5 ppm for 6 to 19
        previous years (DeRose, 1946; Fryer and Kirkland, 1970; Torstensson
        et al.,  1975).  An initial application of MCPA may require up to 20
        weeks for complete dissipation.   In another study, MCPA dissipated
        to nondetectable levels from sandy and silt loam soils  in 30 to 60
        days  (Suzuki,  1977).

        In the aquatic environment, MCPA disipates rapidly (14  to 32 days)
        in water, but residue levels in the flooded soil remain unchanged
        (Soderquist and Crosby, 1974, 1975; Sokolov et al., 1974, 1975).
        A common metabolite,  5-chloro^o-cresol, is formed at low levels
        (1.3% or less) within 1 day of treatment.  Frank et al. (1979) detected
        MCPA  residues (1.1 to 1000 ppb) in 2 of 237 wells in Ontario, Canada,
        between  1969  and 1978.

        In the forest ecosystem, MCPA remains in soil (0 to 3 cm) and leaf
        litter at 0.7 and 32 ppm, respectively, 10 months after application
        at 2.5 kg active ingredient per hectare (ai/ha)  (Eronen et al.,
        1979).   MCPA  residues in moss decline to 7% of the initial  level
        within 40 days.  Residues in soil (3 to 15 cm deep) are not detectable
        after 40 days.

        MCPA  has not  been found in U.S. ground water.

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     MCPA                                                        August, 1987

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III. PHARMACOKINETICS

     Absorption

          0  No information on the absorption of MCPA was found in the available
             literature.

     Distribution

          0  Elo and Yltalo (1979) treated rats with 8 mg of 14c-MCPA [98% active
             ingredient (a.i.)]  intravenously and measured the distribution of
             radioactivity in nine tissues 1.5 hours after treatment.  Highest
             levels were found in plasma,  kidney, lung, liver and heart with
             lesser amounts found in brain/cerebrospinal fluid (CSF), testis and
             muscle.  Prior treatment of rats with MCPA (intravenous injections
             of 25 to 500 mg/kg 3 hours before administration of radiolabeled
             compound or chronic exposure to 500 or 2,500 mg/L in drinking water)
             lead to decreased levels of 14C-MCPA in the plasma and kidney and
             increased levels in brain/CSF.

          0  Elo and Yltalo (1977) treated rats with 8 mg of 14C-MCPA (purity not
             specified) intravenously and measured the distribution of radioactivity
             in brain, CSF, muscle, liver and kidney 1.5 to 120 hours after treat-
             ment.  Prior treatment of rats with MCPA  (subcutaneous injections of
             250 or 500 mg/kg) caused a decrease in the amount of radioactivity
             found in the plasma.  Increased levels were found in other tissues
             with the largest increases found in the CSF (39- to 67-fold) and
             brain (11- to 18-fold).

     Metabolism

          e  MCPA is metabolized by the liver.  Stimulation of microsomal oxidation
             by phenobarbital increases the rate of MCPA breakdown (Buslovich et al.,
             1979).  Gaunt and Evans (1961) found that 5-chloro-methyl-catechol is
             one of the metabolites of MCPA (Hattula et al., 1979).
     Excretion
             In studies by Fjeldstad and Wannag (1977), four healthy human volun-
             teers each ingested a dose of 5 mg of MCPA (purity not specified).
             Approximately 50% (2.5 mg) of the dose was detected in the urine
             within several days.  Urinary levels were not detectable on the fifth
             day following exposure.

             Rats treated orally with MCPA (purity not specified) excreted nearly
             all of the MCPA during the first 24 hours after intake (90% in urine
             and 7% in feces) (Elo, 1976).

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    MCPA                                                        August, 1987

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IV.  HEALTH EFFECTS

    Humans
       Short-term Exposure

         0  Palva et al. (1975)  reported- one case of MCPA (purity not specified)
            exposure (dose and duration not specified) in a farmworker involved in
            spraying operations.   Exposure resulted in reversible aplastic anemia
            as well as muscular weakness,  hemorrhagic gastritis and slight signs
            of liver damage that were later followed by pancytopenia of all of
            the myeloid cell lines.   In a  followup study in the exposed farmer,
            Timonen and Palva (1980)  reported the occurrence of acute myelomono-
            cytic leukemia.

       Long-term Exposure

         0  No information on the human health effects of chronic exposure to
            MCPA was found in the available literature.
    Animals
       Short-term Exposure

         0  Reported acute oral LD50 values for MCPA (purity not specified) in
            mice and rats are 550 mg/kg and 700 mg/kg, respectively (RTECS, 1985).

         0  Gurd et al. (1965) reported an acute oral LD50 value for MCPA  (purity
            not specified) of 560 mg/kg in mice.

         0  Elo et al. (1982) showed that MCPA (sodium salt; 99% a.i.) causes a
            selective damage of the blood-brain barrier.  These authors observed
            that the penetration of intravenous tracer molecules such as 14c-MCPA,
            14C-PABA, 14C-sucrose, 14C-antipyrine and iodinated human albumin
            (125i_HA) in the brain and CSF of MCPA-intoxicated rats (200 to
            500 mg/kg, sc) was increased compared to controls.  The tissue-plasma
            ratios of 14C-sucrose, 14C-antipyrine and 125I-HA treated rats were
            also increased in the brain and CSF of intoxicated animals, but the
            increases were less pronounced than those of 14C-MCPA or 14C-PABA.

         0  In oral studies by Vainio et al. (1983), Wistar rats administered an
            ester of MCPA (purity not specified)  (0, 100, 150 or 200 mg/kg/day),
            5 days per week for 2 weeks, showed hypolipidemia and peroxisome
            proliferation in the liver.  A Lowest-Observed-Adverse-Effect-Level
            (LOAEL) of 100 mg/kg was identified.

       Dermal/Ocular Effects

         0  Raltech (1979) reported acute dermal LDso values for MCPA (purity not
            specified) in rabbits of 4.8 g/kg for males and 3.4 g/kg for females.

         0  In acute dermal studies conducted by Verschuuren et al. (1975), an
            aqueous paste of MCPA (80.6% a.i.) (0.5 g) was applied to the abraded

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MCPA                                                        August, 1987

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        skin of five chinchilla rabbits.  Slight erythema resulted; the
        skin became sclerotic after 5 to 6 days and healed by 12 days.

     0  In subacute dermal studies, Verschuuren et al. (1975) applied an
        aqueous paste of MCPA (80.6% active ingredient; 0, 0.5, 1.0 or 2.0 g)
        five times weekly for 3 weeks to the shaved skin of rabbits.  Slight
        to moderate erythema occurred at all dose levels, and elasticity of
        the skin was decreased.  The effects subsided at 2 weeks post-treatment.
        Weight loss was observed at all dose levels.  High mortality and
        histopathological alterations were observed in the liver, kidneys,
        spleen and thymus at the 1.0- and 2.0-g dose levels.

   Long-term Exposure

     0  Verschuuren et al. (1975) administered MCPA (80.6% a.i.) in the diet
        for 90 days to SPF weanling rats (10/sex/dose) at levels of 0, 50,
        400 or 3,200 ppm.  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
        about 0, 2.5, 20 or 160 mg/kg/day.  Following treatment, growth, food
        intake, mortality, hematology, blood and liver chemistry, organ
        weights and histopathology were measured.  No compound-related effects
        were reported for any of these parameters except for growth retard-
        ation and elevated relative kidney weights at 400 ppm (20 mg/kg/day)
        or more.  A No-Observed-Adverse-Effect-Level (NOAEL) of 50 ppm
        (2.5 mg/kg/day) and a LOAEL of 400 ppm (20 mg/kg/day) were identified.

     *  Holsing and Kundzin (1970) administered MCPA (considered to be 100%
        a.i.) in the diet of rats  (10/sex/dose) for 3 months.  Doses were
        reported as 0, 4, 8 or 16 mg/kg/day; the concentration in the diet
        was not specified.  Following treatment, no compound-related effects
        were observed in the physical appearance, behavior, growth, food
        consumption, survival, clinical chemistry, organ weights, organ-to-
        body weight ratios, gross pathology or histopathology at any dose
        tested, except for increases in kidney weight in males at  16 mg/kg/day.
        A NOAEL of 8 mg/kg/day and a LOAEL of  16 mg/kg/day were identified
        by this study.

     0  Holsing and Kundzin (1968) administered oral doses of MCPA to rats at
        dose levels of 0, 25, 50, and  100 mg/kg/day for  13 weeks.  Cytopatho-
        logical changes in the liver and kidneys were observed at  all doses.
        Kidney effects included focal  hyperplasia of tht< eptithelial  lining,
        interstitial nephritis, tubular dilation and/or  hypertrophy.  A LOAEL
        of  25 mg/kg/day  (the lowest dose tested) is identified by  this study.

     0  Reuzel and Hendriksen  (1980) administered MCPA  (94%  a.i.)  in  feed  to
        dogs in two  separate 13-week studies.  Dosing  regimens of  0,  3, 12 or
        48  mg/kg/day, and 0, 0.3,  1 or  12 mg/kg/day, respectively, were
        employed.  Decreased kidney and liver  function,  characterized by
        increases in blood urea, SGPT  and creatinine were observed at doses
        as  low as  3  mg/kg/day.  Low prostatic  weight and mucopurulent conjunc-
        tivitis were observed at higher doses.  A NOAEL  of  1 mg/kg/day and a
        LOAEL of  3 mg/kg/day were  identified by these studies.

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    0   Hellwig (1986) administered oral doses of MCPA (95% a.i.) to dogs at
        doses of 0, 6, 30, or 150 ppm for 1  year.  Assuming that 1  ppro in the
        diet of dogs is equivalent to 0.025 mg/kg (Lehman,  1959), this corre-
        sponds to doses of 0, 0.15, 0.75 or 1.5 mg/kg/day.   Renal toxicity
        was observed at the two highest doses and was characterized by elevated
        serum levels of creatinine, urea and potassium,  coloration of the
        kidneys and increased storage of pigment in the  renal tubules.  A
        NOAEL of 0.15 mg/kg/day and a LOAEL of 0.75 mg/kg/day were identified
        by this study.

     0  Holsing (1968) administered oral doses of MCPA (considered to be
        100% a.i.) (0, 25, 50 or 75 mg/kg/day) to beagle dogs (three/sex/dose)
        for 13 weeks.  Histopathological changes and alterations in various
        hematologic and biochemical parameters indicative of bone marrow,
        liver and kidney damage were observed at all dose levels.  The
        hematological findings included decreased hematocrit, hemoglobin and
        erythrocyte counts.  Several dogs had elevated blood urea nitrogen,
        serum glutamic-pyruvic transaminase, serum-oxaloacetic transaminase,
        alkaline phosphatase and serum bilirubin.  Histopathological alterations
        were seen in the liver, kidney, lymph nodes, testes, prostate and
        bone marrow.  All dogs of all three groups had various degrees of
        hepatic, renal and bone marrow injury.  A LOAEL  of 25 mg/kg/day (the
        lowest dose tested) was identified.

     0  Gurd et al.  (1965) administered technical MCPA (purity not specified)
        in the feed to rats  (five/sex/dose) for 7 months at dose levels of 0,
        100, 400, 1,000 or 2,500 ppm.  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, 5, 20, 50 or 125 mg/kg/day.  Following treatment, there
        was a marked decrease in body weight gain at 1,000 ppm (50 mg/kg/day)
        or 2,500 ppm  (125 mg/kg/day), and some deaths occurred at 2,500 ppm
        (125 mg/kg/day).  At 400 ppm (20 mg/kg/day) or greater, there was a
        reduction in numbers of red blood cells, hemoglobin content and
        hematocrit.  Relative kidney weights were increased at 100 ppm
        (5 mg/kg/day), but no effects on body weight were evident.  No
        histopathological changes were reported at any dose level tested.
        A LOAEL of 5 mg/kg/day (the lowest dose tested)  was identified.

   Reproductive Effects

     0  No effects on reproduction were found in rats exposed to doses of
        0, 50, 150, or 450 ppm MCPA  (95% a.i.) in the diet over a period of
        two generations  (MacKenzie, 1986).  Assuming that 1 ppm in the diet
        of rats corresponds  to 0.05 mg/kg/day (Lehman, 1959), this corresponds
        to doses of  0, 2.5,  7.5 or 15 mg/kg/day.  Body weight depression was
        observed in the F-\ and F2 generations at the two highest doses.  A
        NOAEL of 15 mg/kg/day was identified for reproductive function, and
        a NOAEL of 2.5 mg/kg/day was identified for fetoxtoxicity (depressed
        weight gain).

   Developmental Effects

     0  Irvine et al. (1980) administered MCPA (purity not specified) (0, 5,
        12,  30 or 75 mg/kg/day) by gavage to rabbits (15 to 18/dose) on days

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  MCPA                                                        August,  1987

                                       -8-
          6 to 18 of gestation.  No fetotoxicity or teratogenicity was observed
          at any dose level tested.  Body weights of the does were markedly
          reduced in the 75 mg/kg/day dosage group.  A fetal NOAEL of 75 mg/kg/day
          and a maternal NOAEL of  30 mg/kg/day were identified.

        0  Irvine (1980) administered MCPA (purity not specified)  (0, 20, 50 or
          125 mg/kg/day) by gavage to pregnant CD rats (16 to 38/dose) on days
          6 to 15 of gestation.  No maternal or fetal toxicity or teratogenic
          effects were observed.   A NOAEL of 125 mg/kg/day (the highest dose
          tested) was identified.

        0  Palmer and Lovell (1971) administered oral doses of MCPA  (75% a.i.;
          0, 5, 25 or 100 mg/kg/day of the active ingredient) to  mice (20/dose)
          on days 6 to 15 of gestation.  Dams were monitored for  pregnancy rate,
          body weight, and gross toxicity; no significant effects were observed.
          At 100 mg/kg/day, fetal  weights were significantly reduced and there
          was delayed skeletal ossification.  A NOAEL of 25 mg/kg/day and a
          LOAEL of 100 mg/kg/day based on fetal weights were identified.

      Mutagenicity

        0  Moriya et al. (1983) reported that MCPA  (purity not specified)  (5,000
          ug/plate) did not produce mutagenic activity in Salmonella typhimurium
          (TA 100, TA 98, TA 1535, TA 1537, TA 1538) and in Escherichia coli
          (WP2 her) either with or without metabolic activation.

        0  In studies conducted by  Magnusson et al.  (1977), there  were no
          effects on chromosome disjunction, loss or exchange in  Drosophila
          fed MCPA (250 or 500 ppm).

        0  In studies by Linnainmaa (1984), no increases were observed in the
          frequency of sister chromatid exchange  (SCE) in blood lymphocytes
          from rats intragastrically administered MCPA  (purity not  specified)
          at 100 mg/kg/day for 2 weeks.  A slight  increase in SCE was observed
          in bone marrow cells from Chinese hamsters given daily  oral doses of
           100 mg/kg for 2 weeks.   In Chinese hamster ovarian cell cultures,
          SCE was slightly increased following treatment with MCPA  (10~5, 10~4,
           10-3^  1 hour) with and  without activation.

      Carcinogenicity
        0  No information on the potential  carcinogenicity of MCPA was found in
           the available literature.   However,  MCPA stimulates liver peroxisomal
           proliferation,  which  has been  implicated in carcinogenicity (Vainio
           et al.,  1983).


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;

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              HA = (NOAEL or LOAEL) x  (BW) = 	 mg/L  (	 ug/L)
                     (UF) x (    L/day)
where:
        NOAEL or LOAEL = No- or Lowest-Observed-Adverse-Effeet-Level
                         in mg/kj bw/day.

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

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

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

One-day Health Advisory

     No information was found in the available  literature that was suitable
for determination of the One-day HA value for MCPA.  It  is therefore  recom-
mended that the Longer-term HA value for  a 10-kj child  (0.1 mg/L, calculated
below) be used at this time as a conservative estimate of the One-day HA value.

Ten-day Health Advisory

     No information was found in the available  literature that was suitable
to serve as the basis for determining the Ten-day HA value for MCPA.   Several
reproductive/teratology studies have been performed in which rats or  rabbits
have been given oral doses of MCPA for acute duration  (Irvine, 1980;  Irvine
et al., 1980; Palmer and Lovell, 1971; MacKenzie, 1986).  The only signs of
maternal toxicity observed in these studies was a reduction in body weight in
rats exposed to 75 mg/kj (Irvine, 1980).  Estimates of maternal  NOAELs  range
from 30 to 125 mg/kj/day (Irvine, 1980;  Irvine et al,  1980).  Fetotoxicity
has been observed at dose levels as low as 7.5 mg/kj/day (MacKenzie,  1986).
The toxicity of MCPA from acute exposure has not been well characterized.  It
is therefore recommended that the Longer-term HA value for a 10-kg child of
(0.1 mg/L, calculated below) be used at this time as a conservative estimate
of the Ten-day HA value.

Longer-term Health Advisory

    Evidence of renal dysfunction has been observed in both 13-week  (Reuzel and
Hendriteen, 1980; Holsing, 1968) and 1-year  (Hellwig,  1986) feeding studies in
beagle dogs and serves as the basis for the Longer-term  HA.  In  subchronic studies
changes in blood urea and creatinine levels have been observed at doses of 25
mg/kj/day (Holsing, 1968) and 3 mg/kj/day (Reuzel and Hendriteen, 1986).  Renal
toxicity is not unique to dogs and has been observed in  rats after 90-day
exposure at dose levels of 20 mg/kj/day  (Verschuuren et  al., 1975) and  25
mg/kj/day (Holsing, 1968),  The rat and dog may have similar sensitivities; a
conservative estimate of the NOAEL was obtained from the studies described by
Reuzel and Hendriteen (1980).  In these studies, oral doses of 0, 3,  12 or 48
mg/kj/day, and 0, 0.3, 1 or 12 mg/kj/day, respectively, were administered to

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                                     -10-
dogs for 13 weeks.  Increases in blood urea, SGPT and creatinine levels were
observed at dose levels as low as 3 mg/Jq/day; low  prostatic weight and
mucopurulent conjunctivitis were observed at higher dose levels.  A NOAEL  of
1 mg/kg/day was identified by these studies.

     Using a NOA^L of 1 mg/Jq/day, the Longer-term  HA for a 10-Jq child is
calculated as follows:

       Longer-term HA = (1.0 mg/Jq/day)  (10  Jq) = Q.10 mg/L (100 ug/L)
                            (100) (1 L/day)
where:
         1.0 mg/Jq/day = NOAEL, based on the absence of renal effects  in  dogs
                        exposed to MCPA in the diet for 90 days.

                 1 0  Jq = assumed body weight of a child.

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

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

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

        Longer-term  HA = (1'° mg/Jq/day)  (70  Jq) = Q%35    /L  (350 ug/L)
                            (100)  (2 L/day)

where:

         1.0 mg/Jq/day = NOAEL, based on  the absence of renal effects  in  dogs
                        exposed to MCPA  in the diet for 90 days.

                 70  Jq = 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 of an  adult.

 Lifetime Health  Advisory

     The Lifetime HA represents that  portion of an individual's total exposure
 that is attributed  to drinJdng 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  IntaJe  (ADI). The RfD is an esti-
 mate of a daily  exposure to the human  population that is  liJely to be without
 appreciable  ris k 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  Drin JcLng Water Equivalent  Level
 (DWEL)  can be determined  (Step 2).  A DWEL is  a medium-specific  (i.e., drinJdng
 water)  lifetime  exposure level, assuming 100%  exposure  from  that medium, at

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                                     -11-
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 chronic toxicity study in dogs (Hellwig, 1986) has been selected to
serve as the basis for the determination of the Lifetime HA.  Beagle ,dogs were
exposed to 0, 6, 30 and 150 ppm (0.15, 0.75, or 3.75 mg/kg/day) for 1 year.
Renal toxicity was observed at the two highest doses and was characterized by
elevated serum levels of creatinine, urea and potassium, coloration of the
kidneys and increased storage of pigment in the renal tubules.  A NOAEL of
0.15 mg/kg/day was identified, which is supported by the findings from
subchronic feeding studies.  From 90-day feeding studies, NOAELs of 1 mg/kg/day
and 2.5 mg/kg/day have been identified for dogs (Reuzel and Hendriksen, 1980)
and rats (Verschuuren et al., 1975), based on the absence of effects on the
kidney seen at higher doses.  In a 7-month feeding study, Gurd (1965) observed
increased kidney weight in rats exposed to doses as low as 5.0 mg/kg/day, the
lowest dose tested.

     Using a NOAEL of 0.15 mg/kg/day, the Lifetime HA is calculated as follows:

Step 1:  Determination of the Reference Dose (RfD)

                  RfD = (0.15 mg/kg/day) = 0.0005 mg/kg/day
                           (100) (3)

where:

        0.15 mg/kg/day = NOAEL, based on the absence of kidney effects in
                         dogs exposed to MCPA in the diet for 1 year.

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

                     3 = additional uncertainty factor, chosen in accordance
                         with U.S. EPA Office of Pesticide Programs (OPP)
                         policy to account for the incomplete database on
                         chronic toxicity.

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

           DWEL = (0.0005 mg/kg/day) (70 kg) = 0>018 mg/L (18 ug/L)
                          (2 L/day)

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    MCPA                                                        August,  1987

                                         -12-


    where:

            0.0005 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 = (0.018 mg/L) (20%) = 0.0036 mg/L  (3.6 ug/L)

    where:

            0.018 = DWEL.

              20% = assumed relative source contribution from water.

    Evaluation of Carcinogenic Potential

          0  No studies on the carcinogenic potential of MCPA were found  in the
            available literature.

          0  The  International Agency for Research on Cancer  (IARC,  T983)  concluded
            that the potential carcinogenicity of MCPA in both humans and laboratory!
            animals was  indeterminate.

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


 VI.  OTHER CRITERIA, GUIDANCE AND STANDARDS

          0  The  National Academy of Sciences has recommended  an ADI of 0.00125
            mg/kg/day and a Suggested-No-Adverse-Response-Level  (SNARL)  of
            0.009 mg/L,  based  on a LOAEL of  1.25 mg/kg/day  in  a  90-day study  in
            rats (NAS,  1977).

          0  Residue tolerances have been established for MCPA  at  0.1  ppm in milk
            and  meat.   Peed and forage residue tolerances range  from 0.1  to
             300  ppm  (U.S. EPA, 1985a).


VII.  ANALYTICAL METHODS

          0  Analysis of  MCPA is by a gas chromatographic  (GC)  method applicable
            to  the determination of certain chlorinated acid pesticides in water
            samples  (U.S. EPA, 1985b).   In  this method, approximately 1 liter of
            sample is acidified.  The compounds are extracted  with  ethyl ether
            using a separatory funnel.   The derivatives are hydrolized with
            potassium hydroxide, and extraneous organic material  is removed by

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      MCPA                                                        August,  1987

                                           -13-
              a solvent wash.   After acidification,  the acids  are  extracted  and
              converted to their  methyl  esters  using diazomethane  as  the  derivatizing
              agent.   Excess reagent is  removed,  and the esters  are determined by
              electron-capture  GC.   The  method  detection limit has been estimated
              at 249  ug/L for MCPA.
VIII.  TREATMENT TECHNOLOGIES

           0   Oxidation by ozone  of  500  mg/L MCPA,  after  50  to  80% disappearance
              of initial compound, produced no  identifiable  degradation  products
              (Legube et al.,  1981).   This indicates  that oxidation  by ozone may
              be a  possible MCPA  removal technique.

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    MCPA                                                        August, 1987

                                         -14-


IX. REFERENCES

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    Elo, H.A.  1976.   Distribution and elimination of 2-methyl-4-chlorophenoxy-
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                                     -15-
Hayes, W.J.  1982.  Pesticides studied in man.  Baltimore, MD:  Williams and
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                                     -16-
MacKenzie, K.M.  1986.  Two-generation study with MCPA in rats.  Final report.
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                                     -17-


STORET.  1987.

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Confidential Business Information submitted to the Office of Pesticide
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