820K88125                                ^ust,  1987

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

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

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

        Health Advisories are developed for one-day, ten-day, longer-term
   (approximately 7 years, or 10% of an individual's lifetime) and lifetime
   exposures based on data describing noncarcinogenic end points of toxicity.
   Health Advisories do not  quantitatively incorporate  any  potential carcinogenic
   risk from such exposure.   For those substances that  are  known or probable
   human carcinogens, according  to the Agency  classification scheme  (Group A or
   B),  Lifetime HAs are not  recommended.  The  chemical  concentration values for
   Group A or B carcinogens  are  correlated with  carcinogenic risk estimates by
   employing a cancer potency (unit risk) value  together with assumptions for
   lifetime  exposure and  the consumption of drinking water.  The cancer unit
   risk is usually derived from  the linear multistage model with 95% upper
   confidence limits.  This  provides a low-dose  estimate of cancer risk to
   humans that is considered unlikely to pose  a  carcinogenic risk in excess
   of the stated values.   Excess cancer ris . «. stimates  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.

    Simazine                                                 August, 1987

         The information used  in preparing this Health Advisory was collected
    primarily from the open literature  and the Simazine Registration Standard
    (U.S. EPA,  1983).
    CAS  No.   122-34-9
    Structural Formula


         0  Aquazine,  Cekusan,  Framed  (discontinued  by Farmoplant),  G-27692,
           Gesatop,  Primatol,  Princep,  Simadex,  Simanex,  Tanzene (Meister,  1984).


           Simazine  is  used  as a  selective  preemergence herbicide for control of
           most  annual  grasses and  broadleaf  weeds  in corn, alfalfa,  established
           bermuda grass,  cherries, peaches,  citrus,  different kinds  of berries,
           grapes, apples, pears, certain nuts,  asparagus,  certain ornamental
           and tree  nursery  stock,  and  in turf grass  soil production  (Meister,
           1984).  It is  also  used  to inhibit the growth of most common forms of
           algae in  aquariums, ornamental fish ponds  and fountains.  At higher
           rates, it is used for  nonselective weed  control  in industrial areas.

    Properties  (Berg, 1984;  Freed,  1976; Windholz et  al., 1983)
            Chemical  Formula
            Molecular Weight                    201.69
            Physical  State  (room  temperature)   White, crystalline solid
            Boiling Point
            Melting Point                       225 to 227°C
            Density                             1.302 g/cm^
            Vapor  Pressure  (20°)                6.1  x 10-9 mm Hg
            Water  Solubility  (20o)              3.5 mg/L
            Log  Octanol/Water Partition
            Taste  Threshold
            Odor Threshold
            Conversion Factor

Simazine                                                 August, 1987



     0  Simazine has been found in 877 of 5,067 surface water samples analyzed
        and in 229 of 2,282 ground water samples (STORET, 1987).  Samples
        were collected at 472 surface water locations and 1,730 ground water
        locations, and simazine was found in 22 states.  The 85th percentile
        of all non-zero samples was 2.18 ug/L in surface water and 1.60 ug/L
        in ground water sources.  The maximum concentration found in surface
        water was 1,300 ug/L, and in ground water it was 800 ug/T.

     0  Simazine has been found in ground water in California, Pennsylvania
        and Maryland; typical positives were 0.2 to 3.0 ppb (Cohen et al., 1986)

Environmental Fate

     0  Simazine did not hydrolyze in sterile aqueous solutions buffered at
        pH 5, 7 or 9 (20°C) over a 28-day test period (Gold et al., 1973).
     0  Under aerobic soil conditions, the degradation of simazine depends
        largely on soil moisture and temperature (Walker, 1976).  In a sandy
        loam soil, half-lives ranged from 36 days to 234 days.  Simazine
        applied to loamy sand and silt loam soils and incubated (25 to 30°C)
        for 48 weeks, dissipated with half-lives of 16.3 and 25.5 weeks,
        respectively (Monsanto Company, date not available).  Simazine degra-
        dation products, 2-chloro-4-ethylamino-6-amino-s-triazine (G-28279^),
        2-chloro-4,6bis(amino)-s-triazine, and several unidentified polar
        compounds were detected 32 and 70 days after a sandy loam soil had
        been treated with !4C-simazine (Beynon et al., 1972).  The degradates
        2-hydroxy-4,6=bis(ethylamino)-s-triazine and 2-hydroxy-4-ethylamino-
        6-amino-s-triazine were also detected in aerobic soil (Keller, 1978).

     0  Under anaerobic conditions,  !4C-simazine had a half-life of 8 to 12
        weeks in a loamy sand soil (Keller, 1978).   The treated soil (10 ppm)
        was initially maintained for 1 month under aerobic conditions,
        followed by 8 weeks under anaerobic conditions (flooded with water
        and nitrogen).  Degradates found included G-28279, 2-caj.oro-4,6-
        bis(amino)-s-triazine, 2-hydroxy-4,6-bis(ethylamino)-s-triazine, and

     0  Simazine is expected to be slightly to very mobile in soils ranging
        in texture from clay to sandy loam based on column leaching, soil
        thin-layer chromatography  (TLC), and adsorption/desorption (batch
        equilibrium) studies.  Using batch equilibrium tests, K
     Simazine                                                 August,  1987

             Simazine, as determined  by  soil  TLC,  is mobile  to  very mobile in sandy
             loam soil (Rf  0.80  to  0.96), and  of  low  to intermediate mobility in
             loam and silty clay loam (Rf  0.45), sandy clay  loam  (Rf 0.51),  silt
             loam {Rf 0.16  to 0.51),  clay  loam  (Rf  0.32 to 0.45)  and silty clay
             (Rf 0.36) soils.  Rf values were positively correlated with soil
             organic matter and  clay  content  (Helling, 1971;  Helling and Turner,

             Based on results of soil column  leaching  studies,  simazine phytotoxic
             residues were  slightly mobile to mobile in soils ranging in texture
             from clay loam to sand (Rodgers, 1968; Harris,  1967;  Ivey and Andrews,
             1965).  Upon application of 18 inches  of  water  to  30-inch soil columns
             containing  clay loam, loam, silt loam  or  fine sandy  loam soils,
             simazine phytotoxic residues  leached  to depths  of  4  to 6, 10 to 12,
             22 to 24, and  26 to 28 inches, respectively  (Ivey  and Andrews,  1965).

             In field studies, simazine  had a half-life of about  30 to 139 days in
             sandy loam  and silt loam soils  (Walker, 1976; Martin et 
    Simazine                                                 August, 1987

            the  167-mg/kg  dose,  while the mono-N-dealkylated metabolite ranged
            from 0.35% at  the  1.7-mg/kg dose to 2.8% at the 167-mg/kg dose.

            Similar results  were obtained by Bohme and Bar (1967), who fed simazine
            (formulation and purity not stated) at levels of 200 or 800 mg/kg to
            albino rats and  at 240 to 400 mg/kg to rabbits.  Of the several
            metabolites identified, all retained the triazine ring intact.  The
            principal species  were the mono- and di-N-dealkylated metabolites.

            Bakke and Robbins  (1968) administered 14c-simazine orally by gelatin
            capsules to goats  and sheep.  The sheep were given simazine labeled
            on the triazine  ring or on the ethylamino side-chain, while goats
            were given the ring-labeled compound only.  Based on the metabolites
            identified in  the  urine of animals receiving the ring-labeled compound,
            there was no evidence to suggest that the triazine ring was metabolized.
            In sheep that  received chain-labeled triazines, at least 40% of the
            ethylamino side-chains were removed.  Using ion-exchange chromatography,
            18 labeled metabolites were found in urine.

            Bohme and Bar  (1967) and Larsen and Bakke (1975) observed that rat
            and  rabbit urinary metabolites from the 2-chloro-s-triazines were all
            2-chloro analogs of their respective parent molecules and none of the
            metabolites contained the 2-hydroxy moiety.  Total N-dealkyla^'on,
            partial N-dealkylation, and N-dealkylation with N-alkyl oxidation
            were suggested as  the major routes of the metabolism of 2-chloro-s-
            triazines in rats  and rabbits.
            No quantitative study of simazine excretion routes in monogastric
            animals  was  found in the available literature.

            Bakke  and  Robbins (1968) studied the excretion  of 14c-simazine in
            goats  and  sheep using triazines labeled on the  ring or on the ethylamino
            side-chains.   Approximately 67 to 77% of the administered ring-labeled
            activity was  found in the urine, and 13 to 25%  was found in the feces.
            Negligible residue was present in the milk immediately after treatment
            and within 48 hours of treatment.

            Hapke  (1968)  reported that simazine residues were present in the
            urine  of sheep for up to 12 days- after administration of a single
            oral dose.  The maximum concentration in the urine occurred from 2
            to 6 days  after administration.
       Long-term  Exposure

         0   There were  124  cases of contact dermatitis noted by Yelizarov (1977)
            in the Soviet Union among workers manufacturing simazine and propazine,

Simazine                                                 August, 1987

        Mild cases lasting 3 or 4 days involved pale pink erythema and slight
        edema.  Serious cases lasting 7 to 10 days involved greater erythema
        and edema, and also a vesiculopapular reaction that sometimes progressed
        to the formation of bullae.
   Short-term Exposure
     0  Oral LDso values for simazine have been reported to be greater than
        5,000 rag/kg in the rat (Martin and Worthing, 1977), the mouse and the
        rabbit (USDA, 1984).

     0  Mazaev (1965) administered a single oral dose of simazine (formulation
        and purity not stated) to rats at 4,200 mg/kg.  Anorexia and weight
        loss were observed, with some of the animals dying in 4 to 1 0 days.
        When 500 mg/kg was administered daily, all the animals died in 11 to
        20 days,  with the time of death correlating with the loss of weight.

     0  Sheep and cattle seem to be much more susceptible than laboratory
        animals to simazine toxicity.  Hapke (1968) reported that a single
        oral dose of simazine, 50% active ingredient (a.i.), as low as
        500 mg/kg was fatal to sheep within 6 to 25 days after administration.
        The animals that survived the exposure were sick for 2 to 4 weeks
        after treatment and showed loss of appetite, increased intake of
        water, incoordination, tremor and weakness.  Some of the animals
        exhibited cyanosis and clonic convulsions.

     0  Palmer and Radeleff (1969) orally exposed cattle by drench to 10 doses
        of simazine SOW (purity not stated) at 10, 25 or 50 mg/kg/day and
        sheep by drench or capsule to 10 doses at 25, 50 or 100 mg/kg.  The
        number of test animals in each group was not stated, and the use of
        controls was not indicated.  Anorexia, signs of depression, muscle
        spasms, dyspnea, weakness and uncoordinated gait were commonly observed
        in treated animals.  Necropsy showed congestion of lungs and kidneys,
        swollen, friable livers, and small, hemorrhagic spots on the surface
        of the lining of the heart.

     0  Palmer and Radeleff (1964) found that repeated oral administration of
        simazine SOW (purity not stated) at either 31 daily doses of 50
        mg/kg or 1 4 dainy doses of 100 mg/kg was fatal to sheep.  Simazine
        was also lethal when administered at 100 mg/day for 14 days by drench
        (Palmer and Radeleff, 1969).

     0  The acute inhalation IX^g value of simazine is reported to be more
        than 2.0 mg/L of air (4-hour exposure) (Weed Science Society of
        America, 1983).

    Dermal/Ocular Effects

     0  The acute dermal toxicity in rabbits is greater than 8,000 mg/kg
        (HAS, 1977).

Simazine                                                 August, 1987

     0  In a 21-day subacute dermal toxicity study in rabbits, Ciba-Geigy
        (1980) reported that 15 dermal applications of technical simazine at
        doses up to 1  g/kg produced no systemic toxicity or any dose-related
        alterations of the skin.

     0  In primary eye irritation studies in rabbits, simazine at 71 mg/kg
        caused transient inflammation of conjunctivae (USDA, 1984).

   Long-term Exposure

     0  Tai et al. (1985a) conducted a 13-week subacute oral toxicity study
        in Sprague-Dawley rats fed technical simazine at 0, 200, 2,000 or
        4,000 ppm in their diets.  Assuming that 1 ppm in the diet of rats is
        equivalent to 0.05 mg/kg/day (Lehman, 1959), these levels correspond
        to doses of about 0, 10, 100 or 200 mg/kg/day.  Significant dose-
        related reductions in food intake, mean body weight and weight gain
        occurred in all treated groups.  Significant weight loss occurred
        in mid- and high-dose animals during the first week of dosing.  At
        13 weeks, various dose-related effects were noted in hematological
        parameters (decreased mean erythrocyte and leukocyte counts and
        increased neutrophil and platelet counts), clinical chemistry (lowered
        mean blood glucose, sodium, calcium, blood urea nitrogen (BUN),
        lactic dehydrogenase (LDH), serum glutamic-oxaloacetic transaminase
        (SCOT) and creatinine and increased cholesterol and inorganic phosphate
        levels), and urinalysis determinations (elevated ketone levels and
        decreased protein levels).  Relative and absolute adrenal, brain,
        heart, kidney, liver, testes and spleen weights increased, and overy
        and heart weights decreased.  Necropsies revealed no gross lesions
        attributable to simazine.  A dose-related incidence of renal calculi
        and renal epithelial hyperplasia were detected microscopically in
        treated rats,  primarily in the renal pelvic lumen and rarely in the
        renal tubules.  Microscopic examinations revealed no other lesions
        that could be attributed to simazine.  It appeared to the authors
        that reduced mean food intake in treated rats was most likely due to
        the unpalatability of simazine.  Lower individual body weights and
        reduced body weight gains paralleled mean food intake in treated
        rats.  The majority of the alterations in clinical chemistry values
        may have been related to reduced food consumption.  Since these
        dietary levels of simazine seriously affected the nutritional status
        of treated rats, the results of this study are of limited value.

     0  Tai et al. (1985b) also conducted a 13-week dietary study with beagle
        dogs fed technical simazine at 0, 200, 2,000 or 4,000 ppm.  Based on
        Lehman (1959), these levels correspond to doses of about 0, 5, 50 or
        100 mg/kg/day.  As in the previously described study in rats, reduced
        daily food consumption was attributed to the palatability of simazine
        in the diet and corresponded with weight loss, decreased weight gain
        and various effects on hematology, clinical chemistry, and urinalysis
        determinations.  Changes in these parameters were generally similar
        to those noted in the rat study (Tai et al., 1985a).  Due to the
        seriously affected nutritional status of the test animals, the results
        of this study are of limited value.

Simazine                                                 August, 1987


     0  Dshurov (1979) studied the histological changes in the organs of
        21 sheep following exposures to simazine (50% a.i.) by gavage at 0,
        1.4, 3.0,  6.0, 25, 50, 100 or 250 mg/kg/day for various time durations
        up to about 22 weeks.  Fatty and granular liver degeneration, diffuse
        granular kidney degeneration, neuronophagia, diffuse glial proliferation
        and degeneration of ganglion cells in the cerebrum and medulla were
        found.  In sheep that died, spongy degeneration, hyperemia and edema
        were observed in the cerebrum; the degree of severity was related  to
        the dose of simazine and the duration of exposure.  *h e thyroid
        showed hypofunction after daily doses of 1.4 to 6.0 mg/kg was admini-
        stered for periods of 63 to 142 days.  The most severe antithyroid
        effect followed one or two doses of 250 mg/kg, which in one sheep
        produced parenchymatous goiter and a papillary adenoma.  This type of
        goiter was also seen in sheep administered simazine at 50 or 100 mg/kg
        once per week for approximately 22 weeks.  Based on these data, a
        Lowest-Observed-Adverse-Effect-Level (LOAEL) of 1.4 mg/kg can be
        identified; however, it is not clear from the study details whether
        the authors considered the 50% formulation when providing the dosage

   Reproductive Effects

     0  Woodard Research Corporation  (1965) reported that no adverse effects
        on reproductive capacity were observed in a three-generation study in
        rats.  In this study, two groups of 40 weanling rats (20/sex) were
        used; one served as the control and the other was fed simazine SOW
        at  100 ppm.  This corresponds to a dose of about 5 mg/kg/day, based
        on the assumptions that 1 ppm in the diet of rats corresponds to
        0.05 mg/kg/day (Lehman, 1959).  After 74 days of dosing, animals were
        paired and mated for 10 days, resulting in F-|a litters.  After weaning
        first litters, parents were remated to produce F-jb litters.  Weanlings
        of parents in the 100 ppm group were divided into two groups and fed
        simazine at 50 ppm  (approximately 2.5 mg/kg/day) or at  100 ppm.
        After 81 days they were mated to produce the F2a and F2b litters.
        F2b weanlings were fed the same dietary levels of simazine  (0, 50
        or  100 ppm).  F2b rats were mated to produce F3a and F3b litters.
        Reproductive performance of rats fed simazine was basically similar
        to  that of controls, and no developmental changes were detected.   The
        No-Observed-Adverse-Effect-Level (NOAEL) for this study is approximately
        5 mg/kg/day.

     0  Dshurov (1979) reported that  repeated administration of simazine (50%
        a.i.) to sheep (6.0 mg/kg for 142 days or 25 mg/kg for  37 to 111 days)
        caused changes in the germinal epithelium of the testes and disturbances
        of  spermatogenesis.

   Developmental Effects

      0  No  treatment-related developmental effects were observed by Newell
        and Oilley  (1978) in  the offspring of rats exposed to simazine at  0,
        17, 77 and  317 mg/m3  via inhalation  for  1 to  3 hours/day on days 7
        through 14  of gestation.

Simazine                                                 August, 1987

     8  Woodard Research Corporation (1965),  as described above in Reproductive
        Effects, conducted a three-generation study in which rats were fed
        simazine 80W in mixed dosage groups of 50 and 100 ppm (approximately
        2.5 and 5 mg/kg/day).  No developmental effects wire noted in the


     0  Simazine has shown negative results in a variety of microbial
        mutagenicity assay systems including tests with -the following
        organisms:  Salmonella typhimurium (Simmons et al., 1979; Commoner,
        1976;  Eisenbeis et al., 1981; Anderson et al., 1972); Escherichia
        coli (Simmons et al., 1978; Fahring,  1974); Bacillus subtilis
        (Simmons et al., 1978); Serratia marcescens (Fahring, 1974); and
        Saccharomyces cerevisiae (Simmons et al., 1978).

     0  Simazine induced lethal mutations in the sex-linked recessive lethal
        test using the fruitfly Drosophila melanogaster (Valencia, 1981).
        In a study reported by Murnik and Nash (1977), simazine increased
        X-linked lethals when injected into male JD. melanogaster, but
        failed to do so when fed to larvae.

     0  There are contradictory data concerning the ability of simazine to
        cause DNA damage.  According to Simmons et al. (1979), simazine
        induced unscheduled DNA synthesis in a human lung fibroblast assay.
        However, in the same test conducted by Waters et al.  (1982), simazine
        showed a negative response.

     0  Simazine does not produce chromosomal effects as indicated by the
        sister-chromatid exchange test and mouse micronucleus assay (Waters
        et al., 1982).


     0  Simazine was not tumorigenic in an 18-month feeding study in mice at
        the highest tolerated dose of 215 mg/kg/day (Innes et al., 1969).  In
        this bioassay of 130 compounds, male and female mice of two hybrid
        strains (C57BL/6 x C3H/Anf)Fi and (C57BL/6 x AKR)F-| were exposed to
        simazine (purity not stated) at the maximum tolerated dose of 215 mg/kg
        by gavage from ages 7 to 28 days.  For the remainder of the study,
        the animals were maintained on a diet with simazine at 215 mg/kg/day.
        Based on information presented only in tabular form, gross necropsy
        and histological examination revealed no significant increase in
        tumors related to treatment with simazine.  Other toxicological data
        were not provided.  This study is not considered to provide adequate
        data to fully assess the carcinogenic potential of simazine.

     0  Hazelton Laboratories  (1960) conducted a 2-year dietary study in
        Charles River rats administered simazine SOW (49.9% a.i.) in the feed
        at 0,  1, 10 .and 100 ppm (expressed on the basis of 100% a.i.).  Based
        on the dietary assumptions of Lehman (1959), these levels are equivalent
        to approximately 0, 0.05, 0.5 and 5 mg/kg/day.  These authors reported
        an excess, of thyroid and mammary tumors in high-dose females.  However,

   Simazine                                                 August, 1987

           complete histopathological details were not provided and statistical
           significance was not evaluated.  Furthermore, the high incidence of
           respiratory and ear infections in all groups renders this study
           unsuitable for evaluating the carcinogenic potential of simazine.

        0  Simazine was found to produce sarcomas at the site of subcutaneous
           injection in both rats and mice (Pliss and Zabezhinsky, 1977; abstract


        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) , 	   „ (	   /L)
                        (UF) x {	 L/day)


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

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

                       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 suitable studies were found in the available literature for  the deter-
   mination of the One-day HA value for simazine.  It is therefore recommended
   that  0.05 mg/L  (50 ug/L), the Drinking Water Equivalent Level (DWEL) calculated
   below and adjusted for a 10-kg child, be used at this time as a conservative
   estimate of the One-day HA value.

   Ten-day Health Advisory

        No suitable studies were found in the available literature for  the deter-
   mination of the Ten-day HA value for simazine.  It is therefore recommended
   that  the adjusted DWEL for a  10-kg child  of 0.05 mg/L  (50 ug/L) be used at
   this  time as a conservative estimate of the Ten-day HA value.

   Longer-term Health Advisory

        No suitable studies were found in the available literature for  the deter-
   mination of the Longer-term HA values  for simazine.  It is therefore recommended

Simazine                                                 August, 1987

                                     -1 1-
that the adjusted DWEL of 0.05 mg/L (50 ug/L) be used at this time as a
conservative estimate of the Longer-term HA value for a 10-kg child and  that
the DWEL of 0.175 mg/L (175 ug/L) be used 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 exposu-*.  The Lifetime HA
is derived in a three-step process.  Step 1 determines the Reference Dose
(RfD), formerly called the Acceptable Daily Intake (ADI).  The RfD is an esti-
mate of a daily exposure to the human population that is likely to be without
appreciable risk of deleterious effects over a lifetime, and is derived  from
the NOAEL (or LOAEL), identified from a chronic (or subchronic) study, divided
by an uncertainty factor(s).  From the RfD, a Drinking Water Equivalent  Level
(DWEL) can be determined (Step 2).  A DWEL is a medium-specific (i.e., drinking
water) lifetime exposure level, assuming 100% exposure from that medium, at
which adverse, noncarcinogenic health effects would not be expected to occur.
The DWEL is derived from the multiplication of the RfD by the assumed body
weight of an adult and divided by the assumed daily water consumption of an
adult.  The Lifetime HA is determined in Step 3 by factoring in other sources
of exposure, the relative source contribution (RSC).  The RSC from drinking
water is based on actual exposure data or, if data are not available, a
value of 20% is assumed for synthetic organic chemicals and a value of 10%
is assumed for inorganic chemicals.  If the contaminant is classified as a
Group A or B carcinogen, according to the Agency's classification scheme of
carcinogenic potential (U.S. EPA, 1986a), then caution should be exercised in
assessing the risks associated with lifetime exposure to this chemical.

     The three-generation reproduction study in rats by Woodard Research
Corporation (1965) has been selected to serve as the basis for calculation
of the DWEL and Lifetime HA for simazine.  In this study, two groups of  40
weanling rats (20/sex) were used; one served as the control, and the other
was fed simazine SOW at 100 ppm (approximately 5 mg/kg/day).  After 74 days
of dosing, animals were paired and mated for 10 days, resulting in F-|a litters.
After weaning first litters, parents were remated to produce F1lD litters.
Weanlings of parents in the 100 ppm group were divided into two test groups:
one group was fed simazine at 50 ppm (about 2.5 mg/kg/day) and the other at
100 ppm.  After 81 days of dosing, animals were mated to produce the F2a and
F2b litters.  The ?2b weanlings were then divided into 50- and 100-ppm dosage
groups.  F2fa rats were mated to produce F3a and F3J-, litters.  Reproductive
performance of rats fed simazine was the same as that of controls, and no
teratological changes were detected.  The NOAEL for this study is approximately
5 mg/kg/day.

It is important to note that,  in this study, rats in the F0 generation were
exposed to simazine at the high dose (100 ppm) only.  However, considering that
the F1 and F2 generations treated with 100 ppm did not reflect any adverse
reproductive effects, this feature of the study design did not seem to affect
the results.  Therefore, the NOAEL of 5 mg/kg/day is used for calculation of
the RfD.

Simazine                                                 August, 1987


Step 1:  Determination of the Reference Dose (RfD)

                     RfD = 5 mg/kg/day = 0.005 mg/kg/day


        5 mg/kg/day = NOAEL for reproductive and developmental  effects in a
                      three-generation rat study.

              1,000 = uncertainty factor, chosen in accordance  with NAS/ODW
                      guidelines for use with a NOAEL from an animal study
                      of less-than-lifetime duration.

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

           DWEL =  (0.005 mg/kg/day) (70 kg) = 0.175 mg/L  (175   /L)
                          (2 L/day)


        0.005 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 = (0.175 mg/L) (20%) = 0.035 mg/L (35 ug/L)


        0.175 mg/L = DWEL.

              20%  = Assumed relative source contribution  from water.

Evaluation of Carcinogenic Potential

      0  Based on the available data, there is no evidence to show  that simazine
        is carcinogenic, and no calculations of carcinogenic risk  factors for
        simazine have been performed.  Neither the study  in mice by Innes
        et al.  (1969) nor the study in rats by Haz^ton Laboratories  (1960)
        is considered adequate for assessment of the carcinogenicity of  this

      0  Simazine is a chloro-s-triazine derivative, with  a chemical structure
        analogous  to atrazine and propazine.  Both these  two structurally-
        related compounds were found to significantly (p  >0.05) increase the
        incidence  of mammary tumors in rats.  The structure-activity relation-
        ship of this group of chemicals indicates that simazine is likely to
        reflect a  similar pattern of.oncogenic response in rats as atrazine
        and propazine.  However, a conclusion on this issue must await the
        completion of a new 2-year oncogenic study in rats.

      Simazine                                                 August,  1987

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


           0  A tolerance level of 10 ug/L has been established for simazine and
              its metabolites in potable water when present as a result of application
              to growing aquatic weeds (U.S. FDA,  1979).

           0  Residue tolerances have been established for simazene alone and the
              combined residues of simazine and its metan^lites in or on various
              raw agricultural commodities (U.S. EPA, 1986b).  These tolerances
              range from 0.02 ppm (negligible) in animal products to 15 ppm in
              various animal fodders.

           0  Analysis of simazine is by a gas chromatographic (GC) method applicable
              to the determination of certain nitrogen-phosphorus-containing
              pesticides in water samples (U.S. EPA, 1986c).  In this method,
              approximately 1  L of sample is extracted with methylene chloride.
              The extract is concentrated and the compounds are separated using
              capillary column GC.  Measurement is made using a nitrogen-phosphorus
              detector.  The method detection limit has not been determined for
              this compound but it is estimated that the detection limits for the
              method analytes are in the range of 0.1 to 2 ug/L.


           0  Treatment technologies which will remove simazine from water include
              activated carbon adsorption; ion exchange; and chlorine, chlorine
              dioxide,  ozone,  hydrogen peroxide and potassium permanganate oxidation.
              Conventional treatment processes were relatively ineffec:i\e in
              removing  simazine (Miltner and Fronk, 1985a).  Limited data suggest
              that aeration would not be effective in simazine removal (ESE,  1984;
              Miltner and Fronk,  1985a).

           0  Baker (1983) reported that a 16.5-inch GAC filter cap using F-300,
              which was placed upon the rapid sand filters at the Fremont, Ohio
              water treatment plant and had  been in service for 30 months, reduced
              the simazine levels by 35 to 89% in the water from  the Sandusky
              River.   Miltner  and Fronk (1985a) developed adsorption capacity data
              using spiked,  distilled water  treated with Filtrasorb 400.   The
              following Freundlich isotherm  values were reported  for simazine:
              K = 490 mg/g;  1/n « 0.56.

           0  At the  Bowling Green,  Ohio water treatment plant, PAC in conjunction
              with conventional treatment achieved an average reduction of 47% of

Simazine                                                  August, 1987

        the simazine levels in the water from the Maumee River (Baker, 1983).
        Miltner and Fronk (1985b) monitored simazine levels at water treatment
        plants, which utilized PAC,  in Bowling Green and Tiffin, Ohio.
        Applied at dosages ranging from 3.6 to 33 mg/L,  the PAC achieved 43
        to 100% removal of simazine with higher percent removals reflecting
        higher PAC dosages.  Andersen (1968) reported that activated charcoal
        (wood charcoal, 300-mesh A.C. from Harrison Clark, Ltd.) was effective
        in "inactivating" simazine when mixed into simazine-treated soils,
        though no quantitative data on simazine concentrations were reported.

     0  Rees and Au (1979) reported that an adsorption column containing XAD-2
        resin removed 81 to 95% of the simazine in spiked tap water.

     0  Turner and Adams (1968) reported that, in a study on the adsorption
        of simazine by ion exchange resins (Sheets, 1959), duolite C-3 cation
        exchange resin removed from solution up to 2,000 ug of simazine per
        gram of resin.  Little adsorption was observed with Duolite A-2 anion
        exchange resin.

     e  Miltner and Fronk (1985b) reported the bench scale testing results of
        the addition of various oxidants to spiked, distilled water.  Chlorine
        oxidation achieved 62 to 74 percent removal of simazine.  However,
        when spiked Ohio River water was treated with smaller chlorine dosages
        during shorter time intervals, less than 17% removal was achieved.
        Chlorine dioxide oxidation of spiked, distilled water achieved only a
        22% removal and achieved 8 to 27% removal of simazine in spiked Ohio
        River water when applied at a smaller dosage over a shorter time
        interval.  Ozonation of spiked, distilled water resulted in a 92%
        removal of simazine.  Oxidation of spiked, distilled water with
        hydrogen peroxide obtained a 19 to 42% removal of simazine, and in
        spiked Ohio River water, a smaller dosage over a shorter time interval
        obtained a simazine removal of 1 to 25%.  Potassium permanganate
        oxidized up to 26% of the simazine present in spiked distilled water.

    Simazine                                                 August, 1987



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Simazine                                                 August,  1987

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Simazine                                                     August, 1987


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Simazine                                                      August,  1987

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