820K88009           DRAFT
                                                            August,  1987
                                 BAYGON  (Propoxur)

                                  Health Advisory
                              Office of Drinking Water
                        U.S.  Environmental Protection Agency
I.  INTRODUCTION
        The Health Advisory  (HA)  Program, sponsored by  the Office  of  Drinking
   Water (ODW),  provides  information on  the health effects, analytical  method-
   ology and treatment technology that would be useful  in dealing  with  the
   contamination of drinking water.  Health Advisories  describe  nonregulatory
   concentrations of drinking water contaminants at which adverse  health effects
   would not be  anticipated  to occur over specific exposure durations.  Health
   Advisories contain a margin of safety to protect sensitive members of the
   population.

        Health Advisories serve  as informal technical guidance  to  assist Federal,
   State and local officials responsible for protecting public  health when
   emergency spills or contamination situations occur.  They are not  to be
   construed as  legally enforceable Federal standards.  The HAs  are subject to
   change as new information becomes available.

        Health Advisories are developed  for one-day, ten-day, longer-term
   (approximately 7 years, or 10% of an  individual's lifetime)  and lifetime
   exposures based on data describing noncarcinogenic end points of toxicity.
   Health Advisories do not  quantitatively incorporate  any potential  carcinogenic
   risk from such exposure.   For  those substances that  are known or probable
   human carcinogens, according  to the Agency  classification scheme  (Group A or
   B), Lifetime  HAs are not  recommended.  The  chemical  concentration  values for
   Group A or B  carcinogens  are  correlated with carcinogenic risk  estimates by
   employing a cancer potency (unit risk) value together with assumptions for
   lifetime exposure and  the consumption of drinking water.  The cancer unit
   risk is usually derived from  the linear multistage model with 95%  upper
   confidence limits.  This  provides a low-dose estimate of cancer risk to
   humans that is considered unlikely to pose  a carcinogenic risk  in  excess
   of the stated values.   Excess  cancer  risk estimates  may also be calculated
   using the One-hit, Weibull, Logit or  Probit models.  There is no current
   understanding of the biological mechanisms  involved  in cancer to suggest that
   any one of these models is able to predict  risk more accurately than another.
   Because each  model is  based on differing assumptions, the estimates  that are
   derived can differ by  several  orders  of magnitude.

-------
    Baygon                                                    August,  1987

                                         -2-


II.  GENERAL INFORMATION AND PROPERTIES

    CAS No.  114-26-1

    Structural  Formula
                  2-( 1 -Me thylethoxy) -phenol  methylcarbamate

    Synonyms

         0  Propoxur (proposed common name);  Aprocarb;  Blattenex;  BAY 39007;
            Bayer 39007;  Pillargon;  Propyon;  Suncide;  Tugon;  QMS 33;  Unden
            (Meister,  1984).

    Uses

         0  A nonfood  insecticide used on humans,  animals and turf grass
            (Meister,  1984).

    Properties  (ACGIH,  1984; Meister, 1984;  and CHEMLAB, 1985)
            Chemical Formula               C
            Molecular Weight               209.24
            Physical State (at 258C)        White to tan crystalline solid
            Boiling Point
            Melting Point                  91 8C
            Density (°C)
            Vapor Pressure (120°C)          0.1  mmHg
            Water Solubility (20°C)         2000 mg/L
            Log Octanol/Water Partition    0.14
              Coefficient
            Taste Threshold
            Odor Threshold
            Conversion Factor
    Occurrence
            Baygon has been found in none of the 58 ground water samples analyzed
            from 55 locations.  No surface water samples were analyzed (STORET,
            1987).
    Environmental Fate
    (Forthcoming from OPP)

-------
     Baygon                                                    August,  1987

                                          -3-


III. PHARMACOKINETICS

     Absorption

          0  Vandekar  et al.  (1971)  administered  a single oral  dose of  1.5 mg/kg
             of  propoxur,  95%  active ingredient (a.i.),  to a 42-year-old male
             volunteer.   About 45% of the dose was recovered in urine within
             24  hours  as o-isopropoxyphenol.   Since vomiting occurred 23 minutes
             after ingestion,  the authors assumed that much of  the dose was expelled
             by  this route,  so the percent actually absorbed could not be calculated.

          0  Chemagro  Corp.  (no date) investigated the dermal absorption of 1^c-
             labeled Baygon  in human subjects.  Baygon (4 ug/cm2,  total dose less
             than 1 mg)  was  applied  to the forearm of the subjects(s) in four tests:
             (1) application to the  skin without  preparation, (2)  application
             after stripping of the  skin with  an  adhesive tape, (3) application
             followed  by occlusion and (4) application followed by induction of
             sweating.   The  amounts  excreted  (route not  specified, but presumably
             in  urine)  after these treatments  were 20, 51, 64 and  18%,  respectively,
             indicating that Baygon  is well absorbed through the skin.

          0  Krishna and Casida (1965) administered single oral doses of 14C-labeled
             Baygon (50 mg/kg) to Sprague-Dawley  rats.  After 48 hours, about 4%
             of  the dose had been excreted in  feces, and the remainder was detected
             in  urine  (64 to 72%), expired air'(26%) or  the body  (4.2 to 7.9%).
             This indicated  that Baygon had been  well absorbed (at least 96%) from
             the gastrointestinal tract.  Similar findings were reported by Foss
             and Krechniak (1980).

     Distribution

          0  Foss and  Krechniak (1980) investigated the  fate of Baygon after oral
             administration  of 50 mg/kg to male albino rats.  Analysis of tissues
             indicated that  Baygon levels were greatest  in the kidneys, with
             somewhat  lower  levels in the liver,  blood and brain.

     Metabolism

          0  Dawson et al. (1964) administered single oral doses of 92.2 mg of
             Baygon (purity  not specified) to  six male volunteers, and single oral
             doses of  50 mg  to three subjects.  Urine samples were collected and
             analyzed  for metabolites.  A material identified as  2-isopropoxyphenol
             was observed in the urine of both groups.  Similar results were
             reported  by Vandekar et al. (1971).

          0  Foss and  Krechniak (1980) investigated the  metabolism of Baygon after
             both oral and intravenous administration of 50 mg/kg to male albino
             rats.  Isopropoxyphenol was detected in tissues 10 minutes following
             administration, and the highest  concentrations were attained between
             30  and 60 minutes after dosing.   This metabolite prevailed in the
             blood and liver,  but in the kidney only unchanged Baygon could be
             detected.   Eight hours  postdosing, only traces of Baygon and its
             metabolites were detected in these tissues.

-------
    Baygon                                                    August,  1987

                                         -4-


         *  Everett and  Gronberg  (1971)  studied  the metabolism of  Baygon in
            Holtzman rats.  Animals  were dosed by gavage with  Baygon (5 to 10
            mg/kg)  labeled with 1 4c  Or  ^H in  the carbonyl or the isopropyl groups.
            Pooled  urine from  eight  rats (four/sex) dosed with 20 mg/kg/day of
            unlabeled Baygon for  4 days  was used to isolate sufficient quantities
            of metabolites for identification of structure.  Results indicated
            that the major pathway of  Baygon  metabolism involved depropylation to
            2-hydroxyphenol-N-methyl carbamate and hydrolysis  of the carbamate to
            isopropoxyphenol.  Minor pathways involved  ring hydroxylation at the
            five- or six-position, secondary  hydroxylation of  the  2'-carbon of
            the isopropoxy group  and N-methyl hydroxylation.   Metabolites that
            contained the 6-hydroxy  group formed N-conjugates, while those that
            contained the 5-hydroxy  group formed 0-glucuronides.
    Excretion
            Dawson et al.  (1964)  reported  that in humans  given a single oral
            doses  of 92.2  mg  Baygon  (purity not specified),  38% of  the dose was
            excreted as phenols  in urine  over  the next 24 hours; most was excreted
            in the first 8 to 10 hours.

            Krishna and Casida (1965)  administered single oral doses of 50 mg/kg
            of 14c-carbonyl-labeled  Baygon to  Sprague-Dawley rats.   After 48
            hours, recovery of label in excretory products was as follows:  64%
            (males) and 72% (females)'in  urine;  4% in feces  (males  and females);
            and 26% in expired carbon  dioxide  (males  and  females).   Residual
            label  in the body was 4.2% (males) and 7.9% (females).   One-third of
            the excreted dose was hydrolyzed,  with most of the remainder being
            intact.

            Everett and Gronberg (1971) reported that 85% of orally administered
            14c-carbonyl-labeled Baygon (5 to  8 mg/kg)  was recovered from Holtzman
            rats within 16 hours of  dosing;  20 to 25% of  the radioactivity appeared
            in the expired air,  and  60% of the radioactivity appeared in the
            urine as conjugates.  Also, Foss and Krechniak (1980) indicated that
            85 to 95% of an oral dose  (50 mg/kg) administered to male albino rats
            was excreted in urine with a  half-life of 0.18 to 0.26  hour.
IV. HEALTH EFFECTS
    Humans
       Short-term Exposure

         0  Vandekar  et al.  (1971)  studied  the acute oral toxicity of Baygon in
            human volunteers.   A 42-year-old man ingested a single oral dose of
            1.5 mg/kg of propoxur (Baygon)  (95% a.i.,  recrystallized).   Cholinergic
            symptoms, including blurred  vision, nausea,  sweating,  tachycardia and
            vomiting, began  about 15  to  20  minutes after exposure.  Effects were
            transient and disappeared within 2 hours.   Cholinesterase (ChE)
            activity  (measured  spectrophotometrically) in red blood cells decreased
            to 27% of control values  by  15  minutes after exposure, and  returned

-------
Baygon                                                    August, 1987

                                     -5-
        to control levels  by 2 hours.   No effect was detected in plasma ChE
        activity.   In a second test,  a single dose of 0.36 mg/kg caused
        short-lasting stomach discomfort, blurred vision and moderate facial
        redness and sweating.  Red  blood cell ChE activity fell to 57% of
        control values within 10 minutes, then returned to control levels
        within 3 hours.

     0  Vandekar et al. (1971) administered five oral doses of 0.15 or 0.20
        mg/kg to male volunteers at half-hour intervals (total dose of 0.75
        or 1.0 mg/kg).  In each subject, a symptomless depression of red
        blood cell ChE was observed;  the lowest level, about 60% of control
        values, was reached between 1  and 2 hours following doses 3, 4 and 5.
        After the  final dose, red blood cell ChE activity rose to control
        levels within about 2 hours.   The authors noted that a dose of Baygon
        was tolerated better if it  was divided into portions and given over
        time than if it was given as  a single dose.

   Long-term Exposure

     0  Davies et al. (1967) described the effects of a large-scale spraying
        operation  in El Salvador in which Baygon (OMS-33, 100% a.i.) was
        used.  The trial was planned  so that medical assistance would be
        available, and appropriate  clinical support could be provided to
        those affected by the spraying.  The total amount of OMS-33 sprayed
        was 345 kg.  Among the spraymen, exposure (expressed in person-days)
        was 70.5;  19 experienced symptoms (26% incidence).  In the general
        population, the exposure was  3,340 person-days, and 35 experienced
        symptoms (1% incidence). The primary symptoms were headache, vomiting
        and nausea.  In the spraymen, the symptoms occurred mostly in the
        first days, with no visible symptoms after this time.  In severe
        cases, atropine was administered as antidote.  It was concluded that
        the acute toxicity symptoms were observed in a low incidence, and
        they were, in general, mild,  evanescent, reversible, responsive to
        small doses of atropine, and tended to occur at the beginning of the
        spray program.

     0  Montazemi (1969) reported on the toxic effects of Baygon on the
        population of 26 villages in Iran that were sprayed with Baygon at
        the rate of 2 g/m2 daily for  18 days.  Selected inhabitants from six
        villages and sprayers were  examined on days 2, 8 and 18 and after
        the completion of the spraying.  Depression of ChE activity was found
        in the inhabitants and in the sprayers, but the sprayers generally
        had more severe symptoms.  Atropine or belladonna was adequate to
        treat those exhibiting symptoms.

Animals

   Short-term Exposure

     0  The acute  oral LD5Q value for technical Baygon (purity not spedified)
        in male and female Sherman  rats was reported to be 83 and 86 mg/kg,
        respectively (Gaines, 1969).   The oral LD5Q was reported to be 32 mg/kg
        in mice and 40 mg/kg in guinea pigs (NIOSH, 1983).

-------
Baygon                                                    August, 1987

                                     -6-
     8  Farbenfabriken Bayer (1961)  determined an oral LD5Q of 100 to 150 mg/kg
        (purity not specified)  in male albino rats.  Severe muscle spasms
        were observed, but no dose-response information was provided.

     0  Eben and Kimmerle (1973)  studied the acute toxicity of Baygon in
        SPF-Wistar rats.  Single  oral doses of propoxur (98.7% a.i.), diluted
        with propylene glycol,  were  given by gavage to groups of three male
        rats at levels of 15, 20, 40 or 60 mg/kg; female rats were given
        doses of 10, 20, 40 or  60 mg/kg.  Cholinesterase levels were measured
        in plasma, erythrocytes and  brain at 10, 20 and 180 minutes after
        dosing.  Maximum ChE depression was observed at 10 and 20 minutes in
        the plasma and erythrocytes, and at 180 minutes in the brain.  The
        inhibition was dose-dependent and a no-effect level was not observed.
        In plasma, ChE was inhibited from 19% (low dose) to 63% (high dose)
        in males and from 0 to  32% in females.  In erythrocytes, ChE was
        inhibited from 27 (low dose) to 63% (high dose) in males and from 15
        to 45% in females.  Based on ChE inhibition, this study identified a
        Lowest-Observed-Adverse-Effect-Level (LOAEL) of 10 mg/kg/day.

     0  Farbenfabriken Bayer (1966)  conducted a 9-week feeding study with
        Bay 39007 (purity not specified) in male and female rats (Elberfeld FB),
        Baygon was included in  the diets of the male animals at dose levels
        of 0, 1,000, 2,000, 4,000 or 8,000 ppm.  Based on the assumption that
        1 ppm in the diet of rats is equivalent to 0.05 mg/kg/day (Lehman,
        1959), this corresponds to doses of 0, 50, 100, 200 or 400 mg/kg/day,
        respectively.  Females  were given only one dose (4,000 ppm).  The study
        was begun when the animals (15/dose level) were 4 weeks of age and
        weighed about 48 g.  In males, food consumption and body weight were
        depressed in a dose-dependent manner.  At the 4,000 and 8,000-ppm
        levels, the males were less lively and exhibited slightly shaggy
        coats.  Gross pathologic examinations of all animals were conducted.
        Two males exposed to 4,000 ppm died during the study, one at 11 days
        (evidence of myocarditis) and one at 23 days.  Two males also died
        at the 8,000-ppm level (at 23 and 25 days); one showed necrotic
        inflammation of the mucosa of the small intestine.  Females  (exposed
        to 4,000 ppm only) displayed decreased food consumption and reduced
        weight gain similar to that seen in exposed males.  One of 15 female
        controls died at day 12  (death attributed to pneumonia), and two of
        15 exposed females died,  one at 7 days and one at 45 days (in this
        rat there was suppuration of the cerebellar bottom).  There were
        apparently no measurements of ChE activity or other clinical tests
        performed during this study.  It was concluded by the authors that
        the observed pathology could not be directly attributed to the presence
        of Baygon in the diet.   Based on gross observations, the No-Observed-
        Adverse-Effect-Level (NOAEL) for male animals was identified as
        2,000 ppm (100 mg/kg/day) and the LOAEL as 4,000 ppm (200 mg/kg/day).
        In females, 4,000 ppm (200 mg/kg/day, the only dose tested) was a
        toxic level.

     0  Eben and Kimmerle (1973)  exposed SPF-Wistar rats (four/sex/dose) by
        gavage to doses of 3, 10 or 30 mg/kg/day of Baygon for 4 weeks.  The
        high-dose animals (30 mg/kg/day) displayed cholinergic symptoms.
        Cholinesterase activity in plasma and red blood cells, measured 15

-------
Baygon                                                    August, 1987

                                     -7-
        minutes after dosing on days 3,  8,  14,  21 and 28,  was generally
        depressed in a dose-related manner  at 10 and 30 mg/kg, but not at the
        3-mg/kg dose.  For example, on day  28,  ChE activity in plasma was
        reduced by 0, 21  or 27% in males and by 14, 27 or 41% in females.  In
        erythrocytes, ChE was inhibited by  9, 24 or 32% in males and by 11,
        32 or 43% in females.  No cumulative toxic effects were observed.
        Based on ChE inhibition, the NOAEL  for this study was 3 mg/kg/day,
        and the LOAEL was 10 mg/kg/day.

   Dermal/Ocular Effects

     0  The acute dermal  LD50 of technical  Baygon (purity not specified) was
        reported to be greater than 2,400 mg/kg for both male and female
        Sherman rats (Gaines, 1969).

     0  Crawford and Anderson (1971) indicated that 500 mg of technical
        Baygon (purity not specified, dissolved in acetone) did not cause
        any skin irritation within 72 hours of its application to the abraded
        or unabraded skin of mature New Zealand White rabbits (six/group).

     0  Heimann (1982) demonstrated that Baygon  (98.8% pure) is not a skin
        sensitizer when tested in guinea pigs.

     0  Crawford and Anderson (1971) instilled 100 mg of technical Baygon
        (purity not specified) in the left  eye of six rabbits.  Examination
        at 48 and 72 hours revealed no evidence of ocular irritation or
        corneal damage.

   Long-term Exposure

     0  Eben and Kimmerle (1973) fed propoxur (98.7% a.i.) to male rats in
        the diet for 15 weeks.  Doses were 0, 250, 750 or 2,000 ppm.  Assuming
        that 1 ppm in the diet is equivalent to  0.05 mg/kg/day (Lehman, 1959),
        this corresponds  to doses of about 0, 12.5, 37.5 or 100 mg/kg/day.
        Assays for ChE activity in plasma,  erythrocytes and brain showed no  .
        constancy of inhibition and no dependence on the administered dose.
        No other details  were given.

     0  Root et al.  (1963) studied the effect of Bayer 39007 added to the
        diet of Sprague-Dawley rats for 16 weeks.  The rats (12/sex/dose,
        weighing 72 to 145 g at the start of the feeding trial) were fed Baygon
        (technical, 95.1% pure) at dose levels of 0, 100, 200, 400 or 800 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, 10, 20 or 40 mg/kg/day.
        Biweekly measurements revealed no changes in growth or food consump-
        tion.  Cholinesterase was assayed in blood, brain and submaxillary
        glands of five animals of each sex at each dose level, and no inhi-
        bition was detected.  Necropies were performed on five animals of
        each sex at the termination of the study, and no significant pathology
        was found.  It was concluded that the NOAEL for the rats was greater
        than 800 ppm (40  mg/kg/day, the highest dose tested).

-------
Baygon                                                    August,  1987

                                     -8-
     0  Suberg and Loeser (1984) conducted a chronic (106-week) feeding study
        of Baygon (99.4% a.i.)  in rats (Elberfeld strain)  at dose levels of
        0, 200,  1,000 or 5,000  ppm.   Based on the assumption that 1 ppm in
        the diet of rats is equivalent to 0.05 mg/kg/day (Lehman, 1959), this
        corresponds to doses of about 0,  10,  50 or 250 mg/kg/day.  There were
        50 rats  of each sex per dose level,  plus an additional 10 of each sex
        for interim autopsies at the end  of  the first year.   At the 200-ppm
        dose,  there was no effect on food consumption or body weight, there
        were no  cholinergic signs, and clinical chemistry, gross pathology,
        histopathology and organ weights  showed no changes from control
        values.   At 1,000 ppm,  retarded weight gain was observed in males
        during the first 20 weeks.   At 1,000 and 5,000 ppm,  there were
        significant hyperplasia of urinary bladder epithelium (described in
        more detail in the Carcinogenicity section) and increased incidence
        of neuropathy.  At the  5,000-ppm  dose, both weight gain and food
        consumption were significantly retarded throughout the study; males
        showed increased thromboplastin time, and females  had consistently
        lower mean plasma ChE activity than  did controls or  other test groups.
        Both sexes showed some  degree of  splenic atrophy,  but there were no
        other significant changes in other organs.  Based  on body weight
        gain,  the NOAEL for this study was identified as 200 ppm (10 mg/kg/day),
        and the  LOAEL as 1,000  ppm  (50 mg/kg/day).

     0  Loser (1968a) conducted a 2-year  feeding study of  Baygon in male and
        female SPF-Wistar rats.  Starting at 1 month of age, the test material,
        BAY 39007 (99.8% a.i.,  technical), was included in the diet at levels
        of 0,  250, 750, 2,000 or 6,000 ppm.   Based on the  assumption that
        1  ppm in the diet of rats is equivalent to 0.05 mg/kg/day (Lehman,
        1959), this corresponds to doses  of  0, 12.5, 37.5,  100 or 300 mg/kg/day.
        The control group consisted  of 50 animals of each sex, while test
        groups contained 25 animals  of each  sex.  Growth and behavior were
        observed, liver function and ChE activity were tested, and blood and
        urine were analyzed periodically.  Necropsies on five animals of each
        sex were conducted at the termination of the experiment.  The major
        adverse  effects noted were  low food  consumption and  low body weight
        in all animals at the 6,000-ppm dose level, and low body weight in
        the female (but not male) animals at the 2,000-ppm dose level.
        Cholinesterase determinations on  blood (measured at  the high dose
        only)  revealed no changes; ChE activity was 9.8 and  9.9 units in
        control  males and females,  respectively, compared with 9.9 and 10,0
        in exposed males and females.  The author indicated  that the methodology
        may have been too insensitive to  detect small changes that may have
        occurred.  No spasms or other symptoms of ChE inhibition were observed.
        No impairment of liver  or kidney  function was detected by clinical
        tests, but necropsy revealed increased liver weight at all doses
        greater  than 250 ppm.  Results of blood analysis were normal at all
        dose levels except at 6,000  ppm.   Apart from increased liver weights,
        necropsy findings were  unremarkable.   Based on increased liver weights,
        this study identified a NOAEL of  250 ppm (12.5 mg/kg/day) and a LOAEL
        of 750 ppm (37.5 mg/kg/day).

     0  Loser (1968b) conducted a 2-year  study of Baygon toxicity in beagle
        dogs.   The product, BAY 39007 (technical, 99.8% pure), was included in

-------
Baygon                                                    August,  1987

                                     -9-
        the diet at levels  of  0,  100,  250,  750 or 2,000 ppm.   Assuming that
        1  ppm in the diet of dogs is equivalent to 0.025 mg/kg/day (Lehman,
        1959),  this corresponds to doses of about 0,  2.5,  6.25,  18.7 or
        50 mg/kg/day.   The  study was begun  when the dogs (four/sex/dose) were
        4 to 5 months old.   Observations on the animals included weight and
        food consumption at periodic intervals, ChE determinations in blood
        at 16 weeks, clinical  evaluations of blood and urine, and tests for
        liver and kidney function.  Necropsies were performed on animals that
        died during the study  and at termination of the study.  The appearance,
        behavior, and food consumption of dogs at the 100,  250 or 750 ppm
        levels were comparable to those of  the controls.  At the 2,000-ppm
        level,  dogs of both sexes appeared  to be weak and sick.   One of the
        males and all four females at this  dose died before completion of the
        study.   During the first 6 months,  dogs at this dose level exhibited
        quivering and spasms,  particularly  in the abdominal region, and food
        consumption was less  than for the controls (especially in females);
        as expected, the dogs  showed statistically significant depression
        in weight gain compared with the controls.  Males,  but not females,
        showed lower weights  than did controls at the 750-ppm dose level, but
        the decrease was not statistically significant.  Clinical analyses
        did not reveal any aberrations in the blood or any changes in liver
        or kidney function.  However,  increased liver weights were observed
        at necropsy, and serum electrophoresis performed at the time of
        sacrifice revealed decreased levels of some serum proteins, inter-
        preted by the author  as reflecting  impaired protein synthesis.
        Cholinesterase determinations in whole blood at 16 weeks did not
        reveal any significant inhibition of activity.  In males, ChE inhibi-
        tion at 100, 250, 750  and 2,000 ppm was 0, 11, 1 and 13%, respectively,
        and in females ChE inhibition was 0, 10, 7 and 0%,  respectively.  The
        author indicated that  the assay method may have been too insensitive
        to detect small changes that may have occurred.  Emaciation was the
        principal finding in  dogs that died during the study; one female had
        abnormal liver parenchyma.  The NOAEL for this study was 250 ppm
        (6.25 mg/kg/day), and  the LOAEL  (based on increased liver weight,
        decreased body weight  and altered blood proteins) was 750 ppm  (18.7
        mg/kg/day).

        Bomhard and Loeser (1981) conducted a 2-year feeding study of propoxur
        (99.5% a.i.) in SPF CFI/W71 mice at dose levels of 0, 700, 2,000 or
        6,000 ppm.  Assuming that 1 ppm  in the diet of mice is equivalent to
        0.15 mg/kg/day (Lehman, 1959), this corresponds to doses of about 0,
        105, 300 or 900 mg/kg/day.  Mice were 5 to 6 weeks of age, weighing
        22 to 25 g at the beginning of the study; each group consisted of 50
        animals of each sex,  plus an additional 10/sex/group included for
        interim autopsy at 1  year.  Body weight gain was slightly depressed
        in male mice at the 6,000-ppm level.  Apart from this observation,
        all aspects of behavior, appearance, food intake, weight and mortality
        were comparable to control values.   Clinical chemistry and blood
        studies, including glucose and cholesterol levels,  were within the
        normal range for all  groups, and there were no significant gross
        pathological or histopathological findings that could be attributed
        to the ingestion of Baygon.  It was concluded that the male mice
        tolerated the pesticide at levels up to and including 2,000 ppm,

-------
Baygon                                                    August, 1987

                                     -10-
        while the female mice tolerated doses up to and including 6,000 ppm
        without adverse effects.   Based on these conclusions, the NOAEL for
        this study was 2,000 ppm  (300 mg/kg/day), and the LOAEL (based on
        depressed weight gain in  males) was 6,000 ppm (900 mg/kg/day).

   Reproductive Effects

     0  No multigeneration studies of the effects of Baygon on reproductive
        function of animals were  found in the available literature.

     0  In a developmental toxicity study in rabbits, Schlueter and  Lorke
        (1981)  observed no adverse effects on several reproductive end points.
        This study is described below.

   Developmental Effects

     0  Schlueter and Lorke (1981) studied the effect of propoxur (99.6% a.i.)
        on Himalayan CHBBsHM rabbits during gestation.  Propoxur was admini-
        stered  by gavage (in 0.5% cremophor) to 15 animals/dose at 0,  1, 3
        or 10 mg/kg.  No adverse  effects were observed in the dams,  and no
        changes were detected in  implantation index, mean placental weight,
        resorption index or litter size.  Embryos were examined for  visceral
        and skeletal defects grossly, then were stained with Alizarin, and
        transverse sections were  prepared using the Wilson technique.   No
        adverse fetal effects were found at any dose level with respect to
        mean fetal weight,  the percent of stunting, the percent of slight
        skeletal deviations, or the malformation index.  These results indicate
        that the NOAEL for maternal toxicity, teratogenicity and fetotoxicity
        is greater than 10 mg/kg/day (the highest dose tested).

     0  Lorke (1971) fed Baygon (technical, 98.4% a.i., 0.82% isopropoxyphenol)
        in the  diet to female FB-30 rats on days 1 to 20 of gestation, at
        levels  of 0, 1,000, 3,000 or 10,000 ppm (10/dose).  Assuming that
        1  ppm in the diet of rats is equivalent to 0.05 mg/kg/day, (Lehman,
        1959),  this corresponds to doses of about 50, 150 or 500 mg/kg/day.
        The rats were 2.5 to 3.5  months of age, weighing 200 to 250  g  at the
        time of the experiment.   Cesarean sections were performed on day 20.
        External and internal examinations on fetuses were performed,  and
        fetuses were subjected to skeletal staining.  At the 3,000-  and
        10,000-ppm dose levels, average fetal weights were significantly
        lower than control values,  but ether fetal measurements were in the
        control range.   No terata were observed at a higher incidence  than in
        the control group.   Data  on fetal ossification were not adequately
        described for an adequate evaluation.  Although this study appears to
        reflect a NOAEL of 1,000  ppm (50 mg/kg/day) based on fetotoxic effects,
        information obtained from this study is limited due to the small
        number  of animals tested  and an apparent dose-related decrease in
        maternal weight gain and  fetal weight at the lowest dose tested
        (although these effects were not statistically significant).

-------
Baygon                                                    August, 1987

                                     -11-


   Mutagenicity

     0  DeLorenzo et al.  (1978)  evaluated the mutagenic properties of Baygon
        and other carbamate pesticides  by use of the Salmonella mutagenicity
        test of Ames.   In assays using  five strains of Salmonella typhimurium,
        no mutagenic activity was obtained with Baygon (with microsomal
        activation).

     0  Moriya et al.  (1983) tested Baygon in five strains of £. typhimurium
        and one strain of Escherichia coli using the Ames technique (without
        metabolic activation) and observed no evidence of mutagenic activity.

     0  Blevins et al. (1977) used five mutants of _S. typhimurium LT2 to
        examine the mutagenic properties of Baygon and other methyl carbamates
        and their nitroso derivatives.   No mutagenic activity was observed
        with Baygon in this experiment using the Ames technique.

   Carcinogenicity

     0  Suberg and Loeser (1984) conducted a chronic (106-week) feeding study
        of Baygon (99.4%  a.i.) in rats  (Elberfeld strain) at dose levels of
        0, 200, 1,000 or  5,000 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 about 0, 10, 50 or 250 mg/kg/day.  The study utilized 50
        rats/sex/dose, plus an additional 10 of each sex included for interim
        necropsies at the end of the first year.  At 5,000 ppm there was
        significant hyperplasia of the  urinary bladder epithelium was noted.
        The incidence at  this dose level after 2 years was 44/49 in males and
        48/48 in females, as compared with 1/49 and 0/49 in control males and
        females, respectively.  At 1,000 ppm, there was a smaller increased
        incidence (10/50  and 5/49 in males and females), respectively.  No
        significant effect occurred at 200 ppm (1/50 and 0/49, males and
        females, respectively).   Bladder papillomas were observed in both
        males (26/57)  and females (28/48) at the highest dose after 2 years.
        In addition, at the 5,000-ppm level, carcinoma of the bladder was
        found in 8/57 males and 5/48 females, and carcinoma of the uterus was
        seen in 8/49 females, as compared with 3/49 for the control group.
        At the mid-dose level (1,000 ppm) only papillomas were noted in one
        male.  The tumors of significance in this study are the  uncommon
        bladder tumors (carcinoma and papillomas) with high incidences at the
        high dose level.   The combined  tumor incidences were 34/57 males and
        33/48 females at  5,000 ppm; 1/59 males and 0/48 females  at 1,000 ppm.
        and none in the 200-ppm or control groups.

     0  Bomhard and Loeser (1981) conducted a 2-year feeding study of propoxur
        (99.5% a.i.) in SPF CFI/W71 mice at dose levels of 0, 700, 2,000 or
        6,000 ppm.  Assuming that 1 ppm in the diet is equivalent to 0.15
        mg/kg/day (Lehman, 1959), this corresponds to doses of about 0, 105,
        300 or 900 mg/kg/day.  Mice were 5 to 6 weeks of age, weighing 22 to
        25 g at the beginning of the study; each group consisted of 50 animals
        of each sex, plus an additional 10/sex/group included for interim
        necropsy at 1  year.  Gross and  histological examination  of tissues
        revealed no evidence of increased tumor frequency.

-------
   Baygon                                                    August,  1987

                                        -12-


V. QUANTIFICATION OF TOXICOLOGICAL EFFECTS

        Health Advisories (HAs)  are generally determined for one-day, ten-day,
   longer-term (approximately 7  years)  and lifetime exposures if adequate data
   are available that identify a sensitive noncarcinogenic end point of toxicity.
   The HAs for noncarcinogenic toxicants are derived using the following formula:

                 HA = (NOAEL or  LOAEL)  X (BW) = 	 mg/L (	   /L)
                        (UF) x (	 L/day)

   where:

           NOAEL or LOAEL = No-  or Lowest-Observed-Adverse-Effect-Level
                            in mg/kg bw/day.

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

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

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

   One-day Health Advisory

        The study by Vandekar et al. (1971) has been selected to serve as the
   basis for determination of the One-day HA for Baygon.  In this study, human
   volunteers who ingested single oral  doses of 0.36 or 1.5 mg/kg displayed
   transient cholinergic signs accompanied by marked (43 and 75%, respectively)
   inhibition of red blood cell  ChE (measured 10 to 15 minutes after  exposure).
   Total doses of 0.75 or 1.0 mg/kg administered in five equal portions over 2
   hours did not cause clinical  signs,  but inhibited red blood cell ChE by about
   40%,   A NOAEL was not identified; 0.36 mg/kg is taken as the LOAEL for bolus
   exposure, and 0.45 mg/kg (three-fifths of a 0.75-mg/kg/day total dose,
   administered in the first 3/5 doses) is the LOAEL when exposure to this
   dose  is spread over several hours.   It should be noted that both values are
   considerably lower than the NOAEL values for Baygon identified in  subchronic
   and chronic feeding studies in animals, especially rodents.  Possible reasons
   for this disparity are that humans may be more sensitive to this chemical
   than  animals are; furthermore, single oral doses probably produce  higher peak
   inhibitions than if the same  total dose is ingested over a longer  period of
   time.  It is also likely that measurement of ChE activity 10 to 15 minutes
   after exposure (as in the case of human studies)  detects peak inhibition,
   while sampling later reveals  smaller effects (due to the reversible nature of
   ChE inhibition with carbamates).  Since a child's exposure is more likely to
   occur in a manner similar to  Vandekar's test, where doses were administered
   in five equal portions over time, the LOAEL of 0.45 mg/kg (three-fifths of a
   0.75  mg/kg total dose) is used for the calculation below:

        The One-day HA for a 10-kg child is calculated as follows:

              One-day HA = (0-45 mg/kg/day) (10 kg)  = 0>045   /L (4Q    /L)
                               (100) (1 L/day)

-------
Baygon                                                    August,  1987

                                     -13-
where:

     0.45 mg/kg/day = LOAEL,  based on an inhibition of 40% in red blood cell
                      ChE activity in humans as determined 10 minutes after
                      oral exposure to three-fifths of a 0.75-mg/kg dose,
                      each fifth given at half-hour intervals, and based on
                      the fact that complete recovery of the ChE activity
                      occurred within 2 hours after administration of the
                      last fifth of the total dose.

              1 0 kg = assumed body weight of a child.

                100 = uncertainty factor, chosen in accordance with NAS/ODW
                      guidelines for use with a LOAEL from a human study.

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

Ten-day Health Advisory

     In addition to human studies by Vandekar et al. (1971) discussed above,
two studies were considered for determination of the Ten-day HA.  In a tera-
tology study in rabbits by Schlueter and Lorke (1981), the NOAEL appeared to
be higher than 10 mg/kg/day,  the highest dose tested.  In a teratology study
in rats by Lorke (1971), the dietary administration of Baygon to animals
during gestation was designed to assess both maternal and fetal effects.
While sufficient data were obtained to derive a NOAEL of 50 mg/kg/day and
a LOAEL of 150 mg/kg/day in rats, it is important to note that a dosage of
50 mg/kg/day was sufficient to kill all female animals in a chronic study in
dogs by Loser (1968b); all deaths occurred before the end of the 2-year study
period.  Because humans appear to be more sensitive to Baygon than animals,
the human study by Vandekar et al. (1971), used in the determination of the
One-day HA value, is also the most suitable study for calculation of the Ten-day
HA.  The two LOAELs identified in this study, 0.36 mg/kg (bolus exposure) and
0.45 mg/kg/day (exposure to three-fifths of a 0.75-mg/kg total dose spread
out over the day) can be approximated to 0.40 mg/kg; this value is used below
for calculation of the Ten-day HA.

     The Ten-day HA for a 10-kg child is calculated as follows:

        Ten-day HA = (0.40 mg/kg/day) (10 kg) = 0>040   /L  (40   /L)
                          (100)  (1 L/day)
where:
        0.40 mg/kg/day = LOAEL, based on mild cholinergic signs and 40%
                         inhibition of red blood cell ChE in humans 10 minutes
                         after a single oral dose.

                 10 kg = assumed body weight of a child.

                   100 = uncertainty factor, chosen in accordance NAS/ODW
                         guidelines for use with a LOAEL from a human study.

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

-------
Baygon      f                                              August,  1987

                                     -14-


Longer-tenn Health Advisory

    No suitable information was found in the available literature  for the
determination of the Longer-term HA value for Baygon.  It is,  therefore,
recommended that the modified Drinking Water Equivalent Level  (DWEL) of
40 ug/L for a 10-kg child be used as a conservative estimate for a Longer-term
exposure.  The DWEL of 100 ug/L, calculated below, should be used  for the
Longer-term value for a 70-kg adult.

Lifetime Health Advisory

     The Lifetime HA represents that portion of an individual's total exposure
that is attributed to drinking water and is considered protective  of noncar-
cinogenic adverse health effects over a lifetime exposure.  The Lifetime HA
is derived in a three-step process.  Step 1 determines the Reference Dose
(RfD), formerly called the Acceptable Daily Intake (ADI).  The RfD is an esti-
mate of a daily exposure to the human population that is likely to be without
appreciable risk of deleterious effects over a lifetime, and is derived from
the NOAEL (or LOAEL), identified from a chronic (or subchronic) study, divided
by an uncertainty factor.  From the RfD,  a Drinking Water Equivalent Level
(DWEL) can be determined (Step 2).  A DWEL is a medium-specific (i.e., drinking
water) lifetime exposure level, assuming 100% exposure from that medium, at
which adverse, noncarcinogenic health effects would not be expected to occur.
The DWEL is derived from the multiplication of the RfD by the assumed body
weight of an adult and divided by the assumed daily water consumption of an
adult.  The Lifetime HA is determined in Step 3 by factoring in other sources
of exposure, the relative source contribution (RSC).  The RSC from drinking
water is based on actual exposure data or, if data are not available, a
value of 20% is assumed for synthetic organic chemicals and a value of 10%
is assumed for inorganic chemicals.  If the contaminant is classified as a
Group A or B carcinogen, according to the Agency's classification  scheme of
carcinogenic potential (U.S. EPA, 1986a), then caution should be exercised in
assessing the risks associated with lifetime exposure to this chemical.

     The 2-year feeding study in dogs by Loser (1968b) and the human study
by Vandekar et al. (1971) have been considered for determination of the
Lifetime HA.  In the 2-year dog study by Loser (1968b), the chronic NOAEL was
identified as 6.25 mg/kg/day and the LOAEL as 18.7 mg/kg/day.  The dog NOAEL
value is supported by the data of Loser (1968a) and of Suberg and  Loeser
(1984), which identified NOAEL values of 12.5 and 10 mg/kg/day, respectively,
in chronic studies in rats.  However, t^e dog appears to be far more sensitive
at the higher doses than are rodents; all female dogs and some of  the males
in the high-dose group, 50 mg/kg/day, died before the end of the study
period, while mild systemic toxicity was noted at this dose level  in rats.
Cholinesterase determinations were not performed in the dog study  for use in
comparison with human data.  Due to the reversible nature of ChE inhibition
by carbamates, a large difference is noted between the dosages that can cause
biologically significant levels of ChE inhibition and the dosages  that can
produce cholinergic symptoms of toxicity (including death).  Hence, in the
absence of ChE data in the dog study, and because of the sensitivity of this
end point in the determination of the toxicity of this chemical, the study by
Vandekar et al. (1971) in humans has been selected to serve as the basis for
the Lifetime HA for Baygon.  This study was discussed in the previous sections

-------
Baygon                                                    August,  1987

                                     -15-


on the One-day and Ten-day HAs.   The 2-year mouse study by Bomhard and Loeser
(1981) was not considered, since the data suggest that the mouse is even less
sensitive than the rat.

     Using a human ChE LOAEL of  0.36 mg/kg/day, the Lifetime HA is calculated
as follows:

Step 1:  Determination of the Reference Dose (RfD)

                  RfD = (0*36 mg/kg/day) = 0.004 mg/kg/day
                             (100)

where:

        0.36 mg/kg/day = LOAEL,  based on mild cholinergic signs and 43%
                         inhibition of red blood cell ChE in a human 10 minutes
                         after a single oral dose.

                   100 = uncertainty factor, chosen in accordance with NAS/ODW
                         guidelines for use with a LOAEL from a human study.

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

           DWEL = (0-004 mg/kg/day) (70 kg) = 0.140 mg/L (140 ug/L)
                          (2 L/day)

where:

        0.004 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 = (0-140 mg/L)  (20%) =  Q.003  ng/L  (3 ug/L)
                                 (10)

where:

        0.140 mg/L = DWEL.

                20% = assumed relative  source contribution  from water.

                10 = additional uncertainty factor in accordance  with ODW
                     policy* to account  for possible  carcinogenicity.

*This  policy is used only for group C  oncogen.   However, since  there  is  a
•potential  that  this chemical may be a  more potent oncogen,  its oncogenic
potency  (qi*) was calculated using  the multistage model  (U.S.   EPA,  1987a).
The q1* was estimated to be  7.9 x  10~3 (mg/kg/day)~1;  if the oncogenic  risk  .
level  associated with the above determined  Lifetime  HA value is computed
using  this q,*, the risk  level would be  7  x 10~7  (7  in 10,000,000).

-------
     Baygon                                                    August, 1987

                                          -16-


     Evaluation of Carcinogenic Potential

          0  Suberg and Loeser (1984)  detected an increased frequency of urinary
             bladder epithelium hyperplasia,  bladder papillomas and carcinomas, and
             carcinoma of the uterus in rats  fed Baygon (250 mg/kg/day) for 2
             years.

          0  Bomhard and Loeser (1981)  did not detect an increased incidence of
             tumors in mice fed Baygon at doses up to 90 mg/kg/day for 2 years.

          e  The International Agency  for Research on Cancer (IARC) has not evalu-
             ated the carcinogenic potential  of Baygon.

          0  Applying the criteria described  in EPA's guidelines for assessment
             of carcinogenic risk (U.S.  EPA,  1986a), Baygon may be classified in
             Group C: possible human carcinogen.  This category is for substances
             with limited evidence of  carcinogenicity in animals in the absence of
             human data.  However, this classification group may be considered
             preliminary at the present (U.S.  EPA, 1987b)  since the U.S. EPA
             Office of Pesticide Programs (OPP) has classified this chemical in
             Group 82:  probable human carcinogen (U.S. EPA, 1987a).  A resolution
             will be reached between OPP and  the Cancer Assessment Group (CAG) in
             the near future.

 VI. OTHER CRITERIA, GUIDANCE AND STANDARDS

          0  Residue tolerances have not been established  for Baygon by the OPP.

          •  The American Conference of Governmental Industrial Hygienists (ACGIH,
             1984) has proposed a threshold limit value of 0.5 mg/m3.

          0  The World Health Organization (WHO) calculated an ADI of 0.02 mg/kg/day
             for Baygon (Vettorazzi and Van den Hurk, 1985).


VII. ANALYTICAL METHODS

          8  Analysis of Baygon is by  a high-performance liquid chromatographic
             (HPLC) procedure used for the determination of N-methyl carbamoyloximes
             and N-methylcarbamates in water  samples (U.S. EPA, 1986b).  In this
             method, the water sample  is filtered and a 400-uL aliquot is injected
             into a reverse-phase HPLC column.  Separation of compounds is achieved
             using gradient elution chromatography.  After elution from the HPLC
             column, the compounds are hydrolyzed with sodium hydroxide.  The
             methyl amine formed during hydrolysis is reacted with o-phthalaldehyde
             (OPA) to form a fluorescent derivative that is detected with a
             fluorescence detector.  The method detection limit has not been
             determined for Baygon, but it is estimated that the detection limits
             for analytes included in  this method are in the range of 0.5 to 3 ug/L.

-------
      Baygon                                                    August, 1987

                                           -17-


VIII. TREATMENT TECHNOLOGIES

           0  Available data indicate granular activated carbon (GAC) adsorption
              to be a  possible Baygon removal technique.

           0  Adsorption of Baygon on GAC proceeds  in accordance with both Freundlich
              and Langmuir isotherms (El-Dib et al.,  1974;  Whittaker et al., 1982).

           0  One full-scale laboratory test was carried out on a commercially
              available system (Dennis et al., 1983;  Kobylinski et al., 1984).
              Different levels of Baygon (20 mg/L,  60 mg/L  and 100 mg/L) were added
              to tap water.  At a flow rate of 67.4 gpm, the column removed 99% of
              the Baygon in 3.5,  8.5,  and 21  hours,  respectively, using only 45 Ib
              of granular carbon.

-------
    Baygon                                                    August,  1987

                                         -18-


IX.  REFERENCES

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

    Blevins,  R.D.,  M.  Lee and J.D Regan.   1977.   Mutagenicity screening of five
         methyl  carbamate insecticides  and their nitroso derivatives using mutants
         of Salmonella typhimurium LT2.  Mutat.  Res. 56:1-6.

    Bomhard,  E., and  E.  Loeser,*   1981.  Propoxur,  the active ingredient of Baygon:
         Chronic toxicity study on mice (two-year feeding experiment).  Bayer
         Report  No.  9954;69686.   Bayer  A.G,  Institut fur Toxicologie.   Unpublished
         study.  MRID  00100546.

    Chemagro  Corporation.*  (no date).   Toxicity study on humans.  Report No. 28374.
         Unpublished study.   MRID 00045091.

    CHEMLAB.   1985.  The Chemical Information System,  CIS,  Inc.,  Bethesda, MD.

    Crawford,  C.R., and  R.H.  Anderson.*  1971.   The skin and eye  irritating
         properties of (R) Baygon technical  and  Baygon 70% WP to  rabbits.  Report
         No.  29706.   Unpublished  study.  MRID 00045097.

    Davies, J.E.,  J.J. Freal and  R.W.  Babione.   1967.   Toxicity studies:  Field
         trial of  OMS-33 insecticide in El Salvador.  Report No.  23933.  World
         Health  Organization.  CDL:091768-F.   Unpublished Study.   MRID 00052281.

    Dawson, J.A.,  D.F. Heath, J.A.  Rose,  E.M. Thain and J.B. Word.  1964.  The
         excretion by  humans of the phenol derived  from 2-isopropoxyphenyl
         N-methylcarbamate.   Bull.  WHO.  30:127-134.

    DeLorenzo, F.,  N.  Staiano,  L. Silengo  and R. Cortese.  1978.   Mutagenicity of
         Diallate,  Sulfallate and Triallate  and  relationship between structure
         and  mutagenic effects  of carbamates  used widely in agriculture.  Cancer
         Res.   38:13-15.

    Dennis, W.H.,  A.B. Rosencrance,  T.M.  Trybus, C.W.R. Wade and  E.A.  Kobylinski.
         1983.  Treatment of pesticide-laden  wastewaters from Army pest control
         facilities  by activated  carbon filtration  using the carbolator treatment
         system.   U.S. Army Bioengineering Research and Development Laboratory,
         Ft.  Detrick,  Frederick,  MD.

    Eben, A.,  and  G.  Kimmerle.*  1973.   Propoxur:  Effect of acute and subacute
         oral  doses  on acetylcholinesterase  activity in plasma, erythrocytes, and
         brain of  rats.   Report No.  4262.   Report No.  39114.  Unpublished study.
         MRID 00055148.

    El-Dib, M.A.,  F.M. Ramadan  and M.  Ismail.  1974.  Adsorption  of sevin and
         baygon  on granular activated  carbon. Water Res.  9:795-798.

-------
Baygon                                                    August, 1987
            f
                                     -19-
Everett,  L.J.,  and R.R.  Gronberg.*  1971.  The metabolic fate of Baygon
     (o-isopropoxyphenylmethyl carbamate) in the rat.  Chemagro Corp. Research
     and  Development Department Report No. 28797.  Unpublished study.  MRID
     00057737.

Farbenfabriken  Bayer.*  1961.  Toxicity of Bayer 39007 (Dr. Bocker 5812315):
     Report No. 6686.  Farbenfabriken Bayer Aktiengesellschaft.  Unpublished
     study.  MRID 00040433.

Farbenfabriken  Bayer.*  1966.  Two-month feeding test with Bayer 39007.  Report
     No.  17466.  Institut fur Toxicologie.  Unpublished study.  MRID 00035412.

Foss, W., and J. Krechniak.   1980.  The fate of propoxur in rat.  Arch. Toxicol.
     4:346-349.

Gaines, T.B.  1969.  Acute toxicity of pesticides.  Toxicol. Appl. Pharmacol.
     14:515-534.

Heimann,  K.  1982.  Propoxur (the active ingredient of Baygon and Unden):
     study of sensitization effects on guinea pigs: Bayer Report No. 11218.
     (Mobay Report 82567, prepared by Bayer AG, Institute fuer Toxikologie).
     Unpublished study.   MRID 00141139.

Kobylinski, E.A., W.H. Dennis and A.B. Rosencrance.  1984.  Treatment of
     pesticide-laden wastewater by recirculation through activated carbon.
     American Chemical Society.

Krishna,  J.G.,  and J.E.  Casida.*  1965.  Fate of the variously labeled methyl-
     and  dimethyl-carbamate-14C insecticide chemicals in rats.  Report No.
     16440.  Unpublished study.  MRID 00049234.

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

Lorke, D.*  1971.  BAY 39007:  Examination for embryotoxic effects among rats.
     Report No. 2388.  Report No. 29035.  MRID 00045094.

Loser, E. *  1968a.  BAY 39007:  Chronic  toxicological studies on rats.  Report
     No.  726.  Report No. 22991.  Unpublished study.  MRID 00035425.

Loser, E. *  1968b.  BAY 39007:  Chronic  toxicological studies on dogs.  Report
     No.  669.  Report No. 22814.  Unpublished study.  MRID 00035423.

Meister,  R., ed.  1984.   Farm chemicals  handbook.  Willoughby, OH:   Meister
     Publishing Company.

Montazemi, K.  1969.  Toxicological studies of Baygon insecticide in
     Shabankareh area, Iran.  Trop. Geogr. Med.  21:186-190.

Moriya, M., T.  Ohta, K.  Wantanabe, T. Miyazawa, K. Kato and Y. Shirasu.  1983.
     Further mutagenicity studies on pesticides in bacterial reversion assay
     systems.  Mutat. Res.   116:185-216.

-------
Baygon                                                    August, 1987

                                     -20-
NIOSH.  1983.  National Institute for Occupational Safety and Health.  Registry
     of toxic effects of chemical substances.  Tatken, R.L., and R.J. Lewis,
     eds.  Cincinnati, OH:  National Institute for Occupational Safety and
     Health.  DHHS (NIOSH) Publication No. 83-107.

Root, M., J. Cowan and J. Doull.*  1963.  Subacute oral toxicity of Bayer 39007
     to male and female female (sic) rats:  Report No. 10685.  Unpublished
     Study.  MRID 00040447.

Schlueter, G., and D. Lorke.*  1981.  Propoxur, the active ingredient of
     Baygon:  Study of embryotoxic and teratogenic effects on rabbits after
     oral administration.  Bayer Report No. 10183; MOBAY ACD Report No. 80034r
     Bayer AG Institut fur Toxicologie.  Unpublished study.  MRID 00100547.

STORET.  1987.

Suberg, H., and H. Loeser.*  1984.  Chronic toxicological study with rats
     (feeding study over 106 weeks):  Report 12870.  Unpublished MOBAY study
     No. 88501 prepared by Bayer Institute of Toxicology.  Unpublished study.
     MRID 00142725.

U.S. EPA.  1986a.  U.S. Environmental Protection Agency.  Guidelines for
     carcinogen risk assessment.  Fed. Reg.  51 {185):33992-34003.
     September 24.

U.S. EPA.  1986b.  U.S. Environmental Protection Agency.  Method #5.  Measure-
     ment of N-methyl carbamoyloximes and N-methylcarbamates in ground water
     by direct aqueous injection HPLC with post column derivatization.
     January 1986 draft.  Cincinnati, OH:  U.S. EPA Environmental Monitoring
     and Support Laboratory.

U.S. EPA.  1987a.  U.S. Environmental Protection Agency.  Qualitative and
     quantitative risk assessment for Baygon.  Office of Pesticide Programs.
     A memo from Bernice Fisher to Dennis Edwards, 4/3/87.

U.S. EPA.  1987b.  U.S. Environmental Protection Agency.  Supplemental
     discussion of Baygon classification.  Cancer Assessment Group.  A memo
     from Arthur Chiu to William H.  Farland, 4/6/87.

Vandekar, M., R. Plestina and K. Wilhelm.  1971.  Toxicity of carbamates for
     mammals.  Bull. WHO.  44:241-249.

Vettorazzi, G. and G.W. Van den Hurk.  1985.  Pesticides Reference Index,
     Joint Meeting on Pesticide Residues (JMPR) 1961-1984.

Whittaker, K.F., J.C. Nye, R.F. Wukash, R.J. Squires,  A.C. York and H.A.
     Razimier.  1982.  Collection and treatment of wastewater generated by
     pesticide application.  U.S. Environmental Protection Agency, Cincinnati,
     OH.  EPA-600/2-82-028.
'Confidential Business Information submitted to the Office of Pesticide
 Programs

-------