August, 1987
SIMAZINE
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 cqntain 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 ris : 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.
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The information used in preparing this Health Advisory was collected
primarily from the open literature and the Simazine Registration standard
(U.S. EPA, 1983).
II. GENERAL INFORMATION AND PROPERTIES
CAS No. 122-34-9
Structural Formula
Cl
2-Chloro-4,6-bis(ethylamino)-1 ,3,5-triazine
Synonyms
0 Aquazine, Cekusan, Framed (discontinued by Farmoplant), G-27692,
Gesatop, Primatol, Princep, Simadex, Simanex, Tanzene (Meister, 1984).
Uses
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 CyH-^ClNs
Molecular Weight 201.69
Physical State (room temperature) White, crystalline solid
Boiling Point
Melting Point 225 to 227°C
Density 1.302 g/cm3
Vapor Pressure (20°) 6.1 x 10-9 mm Hg
Water Solubility (20o) 3.5 mg/L
Log Octanol/Water Partition ' —
Coefficient
Taste Threshold
Odor Threshold , —
Conversion Factor —
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Occurrence
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/I.
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, 14c-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 i-.eluded G-28279, 2-ca.i.oro-4,6-
bis(amino)-s-triazine, 2-hydroxy-4,6-bis(ethylamino)-s-triazine, and
2-hydroxy-4-ethylamino-6-amino-s-triazine.
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^ values
determined for 25 Missouri soils ranged from 1.0 for a sandy loam
to 7.9 for a silty loam (Talbert and Fletchall, 1965). Simazine
adsorption was correlated with soil organic matter content and, to a
lesser extent, with cation exchange capacity (CEC) and clay content
(Talbert and Fletchall, 1965; Helling and Turner, 1968; Helling,
1971). Simazine exhibited low mobility in peat and peat moss (K^
more than 21) and a higher mobility in clay fractions (K
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0 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,
1968).
0 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).
0 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 -AJL., 1975;
Mattson et al., 1969). The degradate, 2-chloro-4-ethylam'no-6-
amino-s-triazine (G-28279) was detected at the 0- to 6-inch depth and
at the 6- to 12-inch depth (Martin et al., 1975; Mattson et al., 1969).
0 Simazine residues (uncharacterized) may persist up to 3 years in soil
under aquatic field conditions. Dissipation of simazine in pond and
lake water was variable, with half-lives ranging from 50 to 700 days.
The degradation compound G-28279 was identified in lake water samples,
but was no more persistent than the parent compound (Flanagan et al.,
1968; Kahrs, 1969; Larsen et aj.., 1966; LeBaron, 1970; Kahrs, 1977;
Smith et al., 1975).
III. PHARMACOKINETIC5
Absorption
0 No quantitative information on the gastrointestinal absorption of
simazine in monogastric mammals was located. Bakke and Robbins (1968)
reported that in goats and sheep, from 67 to 77% of a dose of 14c-
simazine (given orally in gelatin capsules) was excreted in urine.
This suggests that absorption was approximately 70%.
Distribution
0 No studies providing data on the tissue distribution of absorbed
simazine in monogastric mammals were found in the available literature.
Metabolism
0 Bradway and Moseman (1982) administered simazine to male Charles
River rats by gavage. OTwo doses of 0.017, 1.7, 17 or 167 mg/kg
were given 24 hours apart. In 24-hour urine samples, the di-N-dealky-
lated metabolite (2-chloro-4,6-diamino-s-triazine) appeared to be the
major product, ranging from 1.6% at the 1.7 mg/kg-dose to 18.2% at
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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*"f on,
partial N-dealkylation, and N-dealkylation with N-alkyl oxidation
were suggested as the major routes of the metabolism of 2-chloro-s-
tri'azines in rats and rabbits.
Excretion
0 No quantitative study of simazine excretion routes in monogastric
animals was found in the available literature.
0 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.
0 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.
IV. HEALTH EFFECTS
Humans
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,
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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 progress
to the formation of bullae.
Animals
Short-term Exposure
0 Oral LD5Q values for simazine have been reported to be greater than
5,000 mg/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 10 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 14 daily 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 LCso 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
(NAS, 1977).
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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.
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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. Ti 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 10'O mg/kg
once per week for approximately 22 weeks. Based on these data, a
Lowest-Observed-Adverse-Effect-Level (LOAEL) of K4 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
levels.
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 F1a litters. After weaning
first litters, parents were remated to produce F-|D 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 ar»d F2b litters.
F2b weanlings were fed the same dietary levels of simazine (0, 50
or 100 ppm). F2J-, rats were mated to produce F3a and F3D 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.
Developmenta.1 Effects
0 No treatment-related developmental effects were observed by Newell
and Dilley (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.
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0 Woodard Research Corporation (1965), as described above in Reproductive
Effects, conducted a three-generation study in which rats were fed
simazine SOW in mixed dosage groups of 50 and 100 ppm (approximately
2.5 and 5 mg/kg/day). No developmental effects w^re noted in the
offspring.
Mutagenicity
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 _D. 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).
Carcinogenicity
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)F-| 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,
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Simazine August, 1987
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complete hi stopatho logical 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
only) .
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) = _ /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, 1 00 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 1 0-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 1 0-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'
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Simazine August, 1987
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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-p. 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 F-jjj 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 ?2a and
F2b litters. The F2b weanlings were then divided into 50- and 100-ppm dosage
groups. F2b 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 FQ generation were
exposed to simazine at the high dose (100 ppm) only. However, considering that
the F.J and ^2 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.
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Simazine August, 1987
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Step 1: Determination of the Reference Dose (RfD)
RfD = 5 mg/kg/day = 0>005 mg/kg/day
(1,000)
where:
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 2: Determination of the Drinking Water Equivalent Level (DWEL)
DWEL = (Q.005 mg/kg/day) (70 kg) = Q^15 /L (175 /L)
(2 L/day)
where:
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)
where:
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^iton Laboratories (1960)
is considered adequate for assessment of the carcinogenicity of this
substance.
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.
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Simazine August, 1987
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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.
VI. OTHER CRITERIA, GUIDANCE AND STANDARDS ^
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 metao'-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.
VII. ANALYTICAL METHODS
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 hat. 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.
VIII. TREATMENT TECHNOLOGIES
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::ne 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
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Simazine August, 1987
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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-mSsh 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.
0 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 spikea, 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.
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Simazine august, 1987
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*
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