September, 1987
ATRAZINE
Health Advisory
Office of Drinking Water
U.S. Environmental Protection Agency.
DRAFT
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.
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II. GENERAL INFORMATION AND PROPERTIES
CAS No. 1912-24-9
Structural Formula £|
N^^N
H
C,H,-I
I I
H H
2-
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Samples were collected at 1,468 surface water locations and 2,123
ground water locations, and atrazine was found in 36 states. The
85th percentile of all non-zero samples was 2.3 ug/L in surface water
and 1.9 ug/L in ground water sources. The maximum concentration
found in surface water was 400 ug/L and in ground, water it was
1,400 ug/L.
0 Atrazine has been found also in ground water in Pennsylvania, Iowa,
Nebraska, Wisconsin and Maryland; typical positives were 0.3 to 3 ppb
(Cohen et al., 1986).
Environmental Fate
0 An aerobic soil metabolism study in Lakeland sandy loam, Hagerstown
silty clay loam, and Wehadkee silt loam soils showed conversion of
atrazine to hydroxyatrazine, after 8 weeks, to be 38, 40 and 47% of
the amount applied, respectively, (Harris, 1967). Two additional
degradates, deisopropylated atrazine and deethylated atrazine, were
identified in a sandy loam study (Beynon et al., 1972).
0 Hurle and Kibler (1976) studied the effect of water-holding capacity
on the rate of degradation and found a half-life for atrazine of more
than 125 days, 37 days and 36 days in sandy soil held at 4%, 35% and
70% water-holding capacity, respectively.
0 In Oakley sandy loam and Nicollet clay loam, atrazine had a half-life
of 101 and 167 days (Warnock and Leary, 1978).
0 Carbon dioxide production was generally slow in several anaerobic
soils: sandy loam, clay loam, loamy sand and silt loam (Wolf and
Martin, 1975; Goswami and Green, 1971; Lavy et al., 1973).
0 14C-Atrazine was stable in aerobic ground water samples incubated for
15 months at 10 or 25°C in the dark (Weidner, 1974).
0 Atrazine is moderately to highly mobile in soils ranging in texture
from clay to gravelly sand as determined by soil thin layer chroma-
tography (TLC), column leaching, and adsorption/desorption batch
equilibrium studies. Atrazine on soil TLC plates was intermediately
mobile in loam, sandy clay loam, clay loam, silt loam, silty clay
loam, and silty clay soils, and was mobile in sandy loam soils.
Hydroxyatrazine showed a low mobility in sandy loam and silty clay
loam soils (Helling, 1971).
0 Soil adsorption coefficients for atrazine in a variety of soils were:
sandy loam (0.6), gravelly sand (1.8), silty clay (5.6), clay loam
(7.9), sandy loam (8.7), silty clay loam (11.6), and peat (more than
21) (Weidner, 1974; Lavy 1974; Talbert and Fletchall, 1965).
0 Soil column studies indicated atrazine was mobile in sand, fine sandy
loam, silt loan and loam; intermediately mobile in sand, silty clay
loam and sandy loam; low to intermediately mobile in clay loam (Heidner,
1974; Lavy, 1974; Ivey and Andrews, 1964; Ivey and Andrews, 1965).
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0 In a Mississippi field study, atrazine in silt loam soil had a half-
life of less than 30 days (Portnoy, 1978). In a loam to silt loam
soil in Minnesota, atrazine phytotoxic residues persisted for more
than 1 year and were detected in the maximum-depth samples (30 to
42 inches) (Darwent and Behrens, 1968). In Nebraska, phytotoxic
residues persisted in silty clay loam and loam soils 16 months after
application of atrazine; they were found at depths of 12 to 24 inches.
But atrazine phytotoxic residues had a half-life of about 20 days in
Alabama fine sandy loam soil, although leaching may partially account
for this value (Buchanan and Hiltbold, 1973).
0 Under aquatic field conditions, dissipation of atrazine was due to
leaching and to dilution by irrigation water, with residues persisting
for 3 years in soil on the sides and bottoms of irrigation ditches,
to the maximum depth sampled, 67.5 to 90 cm (Smith et al., 1975).
III. PHARMACOKINETICS
Absorption
0 Atrazine appears to be readily absorbed from the gastrointestinal
tract of animals. Bakke et al. (1972) administered single 0.53-mg
doses of 14c-ring-labeled atrazine to rats by gavage. Total fecal
excretion after 72 hours was 20.3% of the administered dose; the
remainder was excreted in urine (65.6%) or retained in tissues (15.8%).
This indicates that at least 80% of the dose was absorbed.
Distribution
0 Bakke et al. (1972) administered single 0.53-mg doses of 1^-ring-
labeled atrazine to rats by gavage. Liver, kidney and lung contained
the largest amounts of radioactivity, while fat and muscle had lower
residues than the other tissues examined.
0 In a metabolism study by Ciba-Geigy (1983a), the radioactivity of
14C-atrazine dermally applied to Harlan Sprague-Dawley rats at
0.25 mg/kg was distributed to a minor extent to body tissues. The
highest levels were measured in liver and muscle at all time points
examined; 2.1% of the applied dose was in muscle and 0.5% in liver
at 8 hours.
0 Khan and Foster (1976) observed that in chickens the hydroxy metabo-
lites of atrazine accumulate in the liver, kidney, heart and lung.
Residues of both 2-chloro and 2-hydroxy moieties were found in chicken
gizzard, intestine, leg muscle, breast muscle and abdominal fat.
Metabolism
0 The principal reactions involved in the metabolism of atrazine are
dealkylation at the C-4 and C-6 positions of the molecule. There is
also some evidence of dechlorination at the C-2 position. These data
were reported by several researchers as demonstrated below.
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Bakke et al. (1972) administered single 0.53-mg doses of 1^-ring-
labeled atrazine to rats by gavage. Less than 0.1% of the label
appeared in carbon dioxide in expired air. Most of the radioactivity
was recovered in the urine (65.5% in 72 hours), including at least 19
radioactive compounds. Approximately 47% of the urinary radioactivity
was identified as 2-hydroxyatrazine and its two mono-N-dealkylated
metabolites. None of the metabolites identified contained the 2-chloro
moiety (which may have been removed via hydrolysis during the isolation
technique or by a dechlorinating enzyme as suggested by the in vitro
studies of Foster et al. (1979), who found evidence for a dechlorinase
in chicken liver homogenates incubated with atrazine.
Bohme and Bar (1967) identified five urinary metabolites of atrazine
in rats: the two monodealkylated metabolites of atrazine, their
carboxy acid derivatives and the fully dealkylated derivative. All
of these metabolites contained the 2-chloro group. The in vitro
studies of Dauterman and Muecke (1974) also found no evidence for
dechlorination of atrazine in the presence of rat liver homogenates.
Similarly, Bradway and Moseman (1982) administered atrazine (50,
5, 0.5 or 0.005 mg/day) for 3 days to male Charles River rats and
observed that the fully dealkylated derivative (2-chloro-4,6-diamino-
s-triazine) was the major urinary metabolite, with lesser amounts of
the two mono-N-dealkylated derivatives.
Erickson et al. (1979) dosed Pittman-Moore mini-pigs by gavage with
0.1 g of atrazine (SOW). The major compounds identified in the urine
were the parent compound (atrazine) and deethylated atrazine (which
contains the 2-chloro substituent).
Excretion
Urine appears to be the principal route of atrazine excretion in
animals. Following the administration of 0.5 mg doses of 14c-ring-
labeled atrazine by gavage to rats, Bakke et al. (1972) reported that
in 72 hours most of the radioactivity (65.5%) was excreted in the
urine, 20.3% was excreted in the feces, and less than 0.1% appeared
as carbon dioxide in expired air. About 85 to 95% of the urinary
radioactivity appeared within the first 24 hours after dosing,
indicating rapid clearance.
Dauterman and Muecke (1974) have reported that atrazine metabolites
are conjugated with glutathione to yield a mercapturic acid in the
urine. The studies of Foster et al. (1979) in chicken liver homo-
genates also indicate that atrazine metabolism involves glutathione.
Ciba-Geigy (1983b) studied the excretion rate of 14c-atrazine from
Harlan Sprague-Dawley rats dermally dosed with atrazine dissolved in
tetrahydrofuran at levels of 0.025, 0.25, 2.5 or 5 mg/kg. Urine and
feces were collected from all animals-at 24-hour intervals for 144
hours. Results indicated that atrazine was readily absorbed, and
within 48 hours most of th«.absorbed dose was excreted, mainly in the
urine and to a lesser extent in the. feces. Cumulative excretion in
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Atrazine September, 1987
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urine and feces appeared to be directly proportional to the administered
dose, ranging from 52% at the lowest dose to 80% at the highest dose.
IV. HEALTH EFFECTS
Humans
Short-term Exposure
0 A case of severe contact dermatitis was reported by Schlichter and
Beat (1972) in a 40-year-old farm worker exposed to atrazine formu-
lation. The clinical signs were red, swollen and blistered hands
with hemorrhagic bullae between the fingers.
Long-term Exposure
0 Yoder et al. (1973) examined chromosomes in lymphocyte cultures
taken from agricultural workers exposed to herbicides including
atrazine. There were more chromosomal aberrations in the workers
during mid-season exposure to herbicides than during the off-season
(no spraying). These aberrations included a four-fold increase in
chromatid gaps and a 25-fold increase in chromatid breaks. During
the off-season, the mean number of gaps and breaks was lower in this .
group than in controls who were in occupations unlikely to involve
herbicide exposure. This observation led the authors to speculate
that there is enhanced chromosomal repair during this period of time
resulting in compensatory protection.
Animals
Short-term Exposure
0 Acute oral LD50 values of 3,000 rag/kg in rats and 1,750 mg/kg in
mice have been reported for technical atrazine by Bashmurin (1974);
the purity of the test compound was not specified.
0 Molnar (1971) reported that when atrazine was administered by gavage
to rats at 3,000 mg/kg, 6% of the rats died within 6 hours, and 25%
of those remaining died within 24 hours. The rats that died during
the first day exhibited pulmonary edema with extensive hemorrhagic
foci, cardiac dilation and microscopic hemorrhages in the liver and
spleen. Rats that died during the second day had hemorrhagic broncho-
pneumonia and dystrophic changes of the renal tubular mucosa. Rats
sacrificed after 24 hours had cerebral edema and histochemical
alterations in the lungs, liver and brain.
• CSE Laboratories (1980) studied the acute oral lethality of atrazine
in Sprague-Dawley rats dosed at 1,500, 1,700, 1,900, 2,000 or
5,000 mg/kg. Deaths occurred within 48 hours in all groups except
for that given the 1,500-mg/kg dose. Toxic signs in other groups
included ataxia, diarrhea, oral discharge and chromorhinorrhea (bloody
nasal discharge).. After 14 days, examination of surviving rats
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revealed that body weights were generally normal, and gross necropsy
revealed no abnormalities.
0 Gaines and Linder (1986) determined the oral LD50 for adult male and
female rats to be 737 and 672 mg/kg respectively and 2,310 mg/kg for
pups. This study also reflected that the dermal LDso for adult rats
was higher than 2,500 mg/kg.
0 An acute dermal 1-05Q value of 7.55 g/kg for technical atrazine applied
to rabbits has been reported (Frear, 1969).
0 Palmer and Radeleff (1964) administered atrazine as a fluid dilution
or in gelatin capsules to Oelaine sheep and dairy cattle. Two doses
of 250 mg/kg atrazine caused death in both sheep and cattle. Sixteen
doses of 100 mg/kg were lethal to one sheep. At necropsy, degeneration
and discoloration of the adrenal glands and congestion in lungs,
liver and kidneys were observed.
0 Palmer and Radeleff (1969) orally administered 10 doses of atrazine SOW
(analysis of test material not provided) by capsule or by drench to sheep
at 5, 10, 25, 50 or 100 mg/kg/day and to cows at 10 or 25 mg/kg/day.
The number of animals in each dosage group was not stated, and the use
of controls was not indicated. Observed effects included muscular
spasms, stilted gait and stance and anorexia at all dose levels in
sheep and at 25 mg/kg in cattle. Necropsy revealed epicardial petechiae
(small hemorrhagic spots on the lining of the heart) and congestion
of the kidneys, liver and lungs. Effects appeared to be dose related.
A Lowest-Observed-Adverse-Effect-Level (LOAEL) of 5 mg/kg/day in
sheep and a No-Observed-Adverse-Effect-Level (NOAEL) of 10 mg/kg/day
in cows can be identified from this study.
0 Bashmurin (1974) reported that oral administration of 100 mg/kg of
atrazine to cats had a hypotensive effect, and that a similar dose in
dogs was antidiuretic and decreased serum cholinesterase activity.
No other details of this study were reported.
Dermal/Ocular Effects
°' In a primary dermal irritation test in rats, atrazine at 2,800 mg/kg
produced erythema but no systemic effects (Hayes, 1982).
0 In primary eye irritation studies, atrazine was described as irritating
when applied at an unspecified concentration in rats (Hayes, 1982).
Long-term Exposure
0 Hazelton Laboratories (1961) fed atrazine to male and female rats for
2 years at dietary levels of 0, 1, 10 or 100 ppm. Based on the
dietary assumptions of Lehman (1959), these levels correspond to
doses of approximately 0, 0.05, 0.50 or 5.0 mg/kg/day. After 65
weeks, the 1.0-ppm dose was increased to 1,000 ppm (50 mg/kg/day) for
the remainder of the study. No treatment-related pathology was found
at 26 weeks, at 52 weeks, at 2 years, or in animals that died and
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were necropsied during the study. Results of blood and urine analyses
were unremarkable. Atrazine had no effects on the general appearance
or behavior of the rats. A transient roughness of the coat and
piloerection were observed in some animals after 20 weeks of treatment
at the 10- and 1 00-ppm levels but not at 52 weeks.. Body weight gains,
food consumption and survival were similar in all groups for 18
months, but from 18 to 24 months there was high mortality due to
infections (not attributed to atrazine) in all groups, including
controls, which limits the usefulness of this study in determining a
NOAEL for the chronic toxicity of atrazine.
0 In a 2-year study by Woodard Research Corporation (1964), atrazine
(SOW formulation) was fed to male and female beagle dogs for 105
weeks at dietary levels of 0, 15, 150 or 1,500 ppm. Based on the
dietary assumptions of Lehman (1959), these levels correspond to
doses of 0, 0.35, 3.5 or 35 mg/kg/day. Survival rates, body weight
gain, food intake, behavior, appearance, hematologic findings,
urinalyses, organ weights and histologic changes were noted. The
15-ppm dosage (0.35 mg/kg/day) produced no toxicity, but the 150-ppm
dosage (3.5 mg/kg/day) caused a decrease in food intake as well as
increased heart and liver weight in females. In the group receiving
1,500 ppm (35 mg/kg/day) atrazine, there were decreases in food
intake and body weight gain, an increase in adrenal weight, a
decrease in hematocrit and occasional tremors or stiffness in the
rear limbs. There were no differences among the different groups in
the histology of the organs studied. Based on these results, a NOAEL
of 0.35 mg/kg/day can be identified for atrazine.
Reproductive Effects
0 A three-generation study on the effects of atrazine on reproduction
in rats was conducted by Woodard Research Corporation (1966). Groups
of 10 males and 20 females received atrazine at dietary levels of 0,
50 or 100 ppm. Based on the dietary assumptions that 1 ppm in the
diet of rats is equivalent to 0.05 mg/kg/day (Lehman, 1959), these
levels correspond to doses of approximately 0, 2.5 or 5 mg/kg/day.
After receipt, animals were fed only half of the dietary levels for
the first 3 weeks and were then changed to the stated levels for 74
days. After 74 days of dosing, rats within each group were paired
for mating. Approximately 13 days after the first weaning, the
females in each group were remated with different males in the same
group. The protocol employed following the first mating was repeated
with the pups from the second mating. After the second weaning, the
parents (F0 generation) were sacrificed and the weanlings (FI^ genera-
tion) were used to form another three groups. The entire series of
tests was repeated following the dosing of the FIO generation with
50 or 100 ppm (2.5 or 5 mg/kg/day) atrazine for 105 days. The F2o
generation was fed atrazine for 75 days and the entire protocol
repeated again. After weaning of the F3O generation, the study was
terminated. There were no adverse effects of atrazine on reproduction
observed during the course of the three-generation study. Atrazine
had no effect on any of the following parameters: mean parental body
weight, survival, appearance, behavior, number of litters/group.
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number of live births, mean body weights at birth and weaning, and
percent of pups alive at weaning. A NOAEL of 100 ppm (5 mg/Jq/day)
was identified for this study. However, the usefulness of this study
is limited due to an alteration of the atrazine content of the diet
during important maturation periods of the neonates.
Developmental Effects
0 In the three-generation reproduction study in rats conducted by
Woodard Research Corporation (1966) (described above), atrazine at
dietary levels of 50 or 100 ppm (2.5 or 5 mg/Jq/day) resulted in no
observed histologic changes in the weanlings and no effects on fetal
resorption. No malformations were observed, and weanling organ
weights were similar in controls and atrazine-treated animals.
Therefore, a NOAEL of 100 ppm (5 mg/Jq/day) was also identified for
developmental effects in this study. However, the usefulness of this
study is limited due to an alteration of the atrazine content of the
diet during important maturation periods of the neonates.
0 Atrazine was administered orally to pregnant rats on gestation days
6 to 15 at 0, 100, 500 or 1,000 mg/Jq (Ciba-Geigy, 1971). The two higher
doses increased the number of embryonic and fetal deaths, decreased
the mean weights of the fetuses and retarded the sJeletal development.
No teratogenic effects were observed, the highest dose (1,000 mg/Jq)
resulted in 23% maternal mortality and various toxic symptoms. The
100 mg/Jq dose had no effect on either dams or embryos and is therefore
the maternal and fetotoxic NOAEL in this study.
0 In a study by Ciba-Geigy (1984a), Charles River rats received atrazine
(97%) by gavage on gestation days 6 to 15 at dose levels or 0, 10, 70,
or 700 mg/Jq/day. Excessive maternal mortality (21/27) was noted at
700 mg/Jq/day, but no mortality was noted at the lower doses; also
reduced weight gains and food consumption were noted at both 70 and
700 mg/Jq/day. Developmental toxicity was also present at these dose
levels. Fetal weights were severely reduced at 700 mg/Jq/day; delays
in sJeletal development occurred at 70 mg/Jq/ day, and a dose-related
runting was noted at 10 mg/Jq/day and above. The NOAEL for maternal
toxicity appears to be 10 mg/Jq/day, hower, this is also the LOAEL
for developmental effects.
0 New Zealand white rabbits received atrazine (96%) by gavage on gestation
days 7 through 19 at dose levels of 0, 1, 5 or 75 mg/Jq/day (Ciba-Geigy,
(1984b). Maternal toxicity, evidenced by decreased body weight gains
and food consumption, was present in the mid- and high-dose groups.
Developmental toxicity was demonstrated only at 75 mg/Jq/day by an
increased resorption rate, reduced fetal weights, and delays in
ossification. No teratogenic effects were indicated. The NOAEL
appears to be 1 mg/Jq/day.
0 Peters and Cook (1973) fed atrazine to pregnant rats (four/group)
at levels of 0, 50, 100, 200, 300, 400, 500 or 1,000 ppai in the diet
throughout gestation. The authors assumed a body weight of 300 g and
a daily food consumption of 12 g (based on Arrington, 1972); thus,
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these levels correspond to approximately 0, 2, 4, 8, 12, 16, 20 or
40 mg/Jgg/day. The number of pups per litter was similar in all
groups, and there were no differences in weanling weights. This
study identified a NOAEL of 40 mg/kg/day for developmental effects.
In another phase of this study, the authors demonstrated that sub-
cutaneous (sc) injections of 50, 100 or 200 mg/kj atrazine on gestation
days 3, 6 and 9 had no effect on the litter size, while doses of 800
or 2,000 nig/kg were embryotoxic. Therefore, a NOAEL of 200 mg/kg by
the sc route was identified for embryotoxicity.
Mutagenicity
0 Loprieno et al. (1980) reported that single doses of atrazine
(1,000 mg/kg or 2,000 mg/kg, route not specified) produced bone marrow
chromosomal aberrations in the mouse. No other details of this study
were provided.
0 Murnik and Nash (1977) reported that feeding 0.01% atrazine to male
Drosophila melanogaster larvae significantly increased the rate of
both dominant and sex-linted recessive lethal mutations. They stated,
however, that dominant lethal induction and genetic damage may not be
directly related.
0 Adler (1980) reviewed unpublished work on atrazine mutagenicity
carried out by the European Economic Community. Mutagenic activity
was not induced when mammalian liver enzymes (S-9) were used; however,
the use of plant microsoraes produced positive results. Also, in
in vivo studies in mice, atrazine induced dominant lethal mutations
and increased the frequency of chromatid breaks in bone marrow.
Hence, the author suggested that activation of atrazine in mammals
occurs independently of the liver, possibly in the acidic part of the
stomach.
0 As described previously, Yoder et al. (1973) studied chromosomal
aberrations in the lymphocyte cultures of farm workers exposed to
various pesticides including atrazine. During mid-season a 4-fold
increase in chroma tid gaps and a 25-fold increase in chroma tid breaks
was observed. During the off-season (no spraying), the number of
gaps and breaks was lower than in controls, suggesting to the authors
that there is enhanced chromosomal repair during the unexposed period.
Carcinogenicity
0 Innes et al. (1969) investigated the tumorigenicity of 120 test com-
pounds including atrazine in mice. Two F^ hybrid stocks (C57BL/6 x AnF
and C57BL/6 x AKR) were used. A dose of 21.5 mg/kj/day was administered
by gavage to mice of both sexes from age 7 to 28 days. After weaning
at 4 weeks, this dose level was maintained by feeding 82 ppn atrazine
ad libitum in the diet for 18 months. At necropsy, thoracic and
abdominal cavities were examined, and histologic studies were performed
on all major organs and grossly visible lesions. Blood smears were
examined if the mice showed signs of splenomegaly or lymphadenopathy.
The incidence of hepatomas, pulmonary tumors, lymphomas and total
tumors in atrazine-treated mice was not significantly different from
that in the negative controls.
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0 In data supplied to EPA (U.S. EPA, 1986a) in support of pesticide
registration for atrazine, Ciba-Geigy Corporation (1985) submitted
preliminary summary incidence information (1-year interim report)
on the histopathological findings of their 2-year oncogenicity study
of atrazine in Spraque-Dawley rats. The summary tables contained
indications of increased numbers of tumors in the mammary glands of
the female rats. "Hie statistical evaluation of this preliminary
data raised concerns of a dose-related response for increases in _
mammary tumors. Unfortunately, the data are of a preliminary nature
and cannot be used for any further conclusions in this document before
the 2-year study is completed and evaluated. However, a subsequent
briefing paper by Ciba-Geigy (1987) indicated that this study is
positive. The evaluation of the recently submitted final report of
this 2-year rat study will be performed at a later date.
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 ( u /L)
(UF) x ( L/day)
where:
NOAEL or LOAEL = No- or Lowest-Observed-Adverse-Effect-Level
in mg/kj bw/day.
BW - assumed body weight of a child (10 kj) or
an adult (70 kj ).
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 information was found in the available literature for the
determination of the One-day HA value for atrazine. It is, therefore, recom-
mended that the Ten-day HA value calculated below for a 10-kj child of
0.1 mg/L (100 ug/L), be used at this time as a conservative estimate of the
One-day HA value.
Ten-day Health Advisory
Two teratology studies by Ciba-Geigy one inthe rat (1984a) and one in the
rabbit (1984b) were considered for the calculation of the Ten-day HA value.
The rat study reflected a NOAEL of 10 mg/kj/day for maternal toxicity but this
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Atrazine September, 1987
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value was also the LOAEL for developmental toxicity while the rabbit study
reflected NOAELs of 5 mg/kg/day for developmental toxicity and 1 .mg/hj/day for
maternal toxicity. Thus, the rabbit appears to be a more sensitive species than
the rat for internal toxicity, hence, the rabbit study with a NOAEL of 1 ing/kg/day
is used in the calculations below.
The Ten-day HA for a 10 kg child is calculated below as follows:
(1 mg/kg/d) x (10kg) = n.-i ma/T. (inn mj/T.j
(100 )x (1 L/day)
where:
1 mg/kg/day = NOAEL, based on maternal toxicity evidenced by decreased
body weight gain and food consumption.
10 kj = assumed body weight of a child
100 = uncertainty factor, chosen in accordance with ODW/NAS guidelines
for use with a NOAEL from an animal study.
1 L/d = assumed daily consumption for a child
Longer-term Health Advisory
No suitable information was found in the available literature for the
determination of the longer-term HA value for atrazine. It is, therefore,
recommended that the adjusted DWEL for a 10-kg child of 0.035 mg/L
(35 ug/L) and the DWEL for a 70-Jq adult of 0.123 mg/L (123 ug/L) be used at
this time as a conservative estimate of the Longer-term HA values.
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 IntaJe (ADI). The RfD is an esti-
mate of a daily exposure to the human population that is liJely 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 DrinIcing 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%
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Atrazine September, 1987
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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, 1986b), then caution should be exercised in
assessing the risks associated with lifetime exposure to this chemical.
The 2-year feeding study in dogs by Woodard Research Corporation
(1964) has been selected to serve as the basis for the calculation of the
Longer-term HA, as well as the DWEL, and Lifetime HA. Atrazine (SOW formulation)
was fed to male and female beagle dogs for 105 weeks at nominal doses of 15,
150 or 1,500 ppm; based on measured analytical concentrations of 14.1, 141
and 1,410 ppm, however, these values correspond to approximately 0.35, 3.5
and 35 mg/kg/day (Lehman, 1959). Survival rate, body weight gain, food
intake, behavior, appearance, hematology, urinalysis, organ weights and
histology were determined. The 15-ppm dosage (0.35 mg/kg/day) produced no
toxicity, but the 150-ppm dosage (3.5 mg/kg/day) caused a decrease in food
intake as well as increased heart and liver weight in females. In the group
receiving 1,500 ppm (35 mg/kg/day), there were decreases in food intake and
body weight gain, an increase in adrenal weight, a decrease in hematocrit and
occasional tremors or stiffness in the rear limbs. There were no differences
among the different groups in the histology of the organs studied. Based on
these results, a NOAEL of 0.35 mg/kg/day was identified for atrazine. This
NOAEL is supported by the available preliminary data by Ciba-Geigy (1985) on
a new two-year study in the Sprague-Dawley rats that will be completed for
the Agency review in the near future. This preliminary data reflected adverse
effects (mammary gland tumors) at 70 ppm (3.5 mg/kg/day) but no effects were
were noted at the lower dose level, 10 ppm (0.5 mg/kg/day). Other studies
(Woodard Research Corporation, 1966; Hazelton Laboratories, 1961) identified
long-term NOAEL values of 5 to 50 mg/kg/day and were not considered to be as
protective as the Woodard Research Corporation (1964) study in the dog for
use in calculating the HA values for atrazine.
Step 1: Determination of the Reference Dose (RfD)
RfD = (0.35 mg/kg/day) . 0.0035 mg/kg/day
where:
0.35 mg/kg/day = NOAEL, based on the absence of adverse clinical,
hematological, biochemical and histopathological
effects in dogs.
100 = uncertainty factor, chosen in accordance with ODW/NAS
guidelines for use with a NOAEL from an animal study.
Step 2: Determination of the Drinking Water Equivalent Level (DWEL)
DWEL = (0.0035 mg/kg/day) (70 kg) = 0.123 /L (123 /L)
(2 L/day).
where:
0.0035 mg/kg/day = RfD.
70 kg = assumed body weight of an adult.
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Atrazine September, 1987
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2 L/day = assumed daily water consumption of an adult.
Step 3: Determination of the Lifetime Health Advisory
Lifetime HA = (0.123 mg/L) (20%) = 0.0025 mg/L (3 ug/L)
where:
0.123 mg/L = DWEL.
20% « assumed relative source contribution from water.
10 = additional uncertainty factor, according to ODW policy,
to account for possible carcinogenicity.
Evaluation of Carcinogenic Potential
0 Preliminary data submitted by Ciba-Geigy Corporation (1985) in support
of the pesticide registration of atrazine indicate that atrazine
induced an increased incidence of mammary tumors in female Sprague-
Dawley rats. These findings have been further confirmed in a briefing
by Ciba-Geigy (1987) on the recently completed study. An evaluation
of this study will be performed in the near future.
0 The International Agency for Research on Cancer has not evaluated the
carcinogenic potential of atrazine.
0 Applying the criteria described in EPA's guidelines for assessment of
carcinogenic risk (U.S. EPA, 1986b), atrazine may be classified in
Group C: possible human carcinogen. This category is used for
substances with limited evidence of carcinogenicity in animals in the
absence of human data. This classification is considered preliminary
until the Office of Pesticide Program completes a peer review of the
weight of the evidence for atrazine and its analogs. At present, ODW
has determined that at least one closely related analog, propazine,
is a group C oncogen based on an increased incidence of tumors in the
same target tissue (mammary gland) and animal species (rat) as was
noted for atrazine.
VI. OTHER CRITERIA, GUIDANCE AND STANDARDS
0 Toxicity data on atrazine were reviewed by the National Academy of
Sciences (NAS, 1977), and the study by Innes et al. (1969) was used
to identify a chronic NOAEL of 21.5 mg/kg/day. Although at that time
it was concluded that atrazine has low chronic toxicity, an uncertainty
factor of 1,000 was employed in calculation of the ADI from that
study, since only limited data were available. The resulting value
(0.021 mg/kg/day) corresponds to an ADI of 0.73 mg/L in a 70-kg adult
consuming 2 L of water per day.
0 Tolerances for atrazine alone and the combined residues of atrazine
and its metabolites in or on various raw agricultural commodities
have been established (U.S. EPA, 1986c). These tolerances range from
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Atrazine September, 1987
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0.02 ppm (negligible) in animal products (meat and meat by-products)
to 15 ppm in various animal fodders.
VII. ANALYTICAL METHODS
0 Analysis of atrazine is by a gas chromatographic (GC) method applicable
to the determination of certain nitrogen-phosphorus containing pesti-
cides in water samples (U.S. EPA, 1986d). 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.
VIII. TREATMENT TECHNOLOGIES
0 Treatment technologies which will remove atrazine from water include
activated carbon adsorption, ion exchange, reverse osmosis, ozone
oxidation and ultraviolet irradiation. Conventional treatment methods
have been found to be ineffective for the removal of atrazine from
drinking water (ESE, 1984; Miltner and Fronk, 1985a). Limited data
suggest that aeration would not be effective in atrazine removal
(ESE, 1984; Miltner and Fronk, 1985a).
0 Baker (1983) reported that a 16.5-inch GAG filter cap using F-300,
which was placed upon the rapid sand filters at the Fremont, Ohio
water treatment plant, reduced atrazine levels by 30 to 64% in the
water from the Sandusky River. At Jefferson Parish, Louisiana,
Lykins et al. (1984) reported that an adsorber containing 30 inches
of Westvaco wv-G® 12 x 40 GAG removed atrazine to levels below
detectable limits for over 190 days.
0 At the Bowling Green, Ohio water treatment plant, PAG in combination
with conventional treatment achieved an average reduction of 41% of
the atrazine in the water from the Maumee River (Baker, 1983).
Miltner and Fronk (1985a) reported that in jar tests using spiked
Ohio River water with the addition of 16.7 and 33.3 mg/L of PAC and
1 5-20 mg/L of alum, PAC removed 64 and 84%, respectively, of the
atrazine. Higher percent removals reflected higher PAC dosages.
Miltner and Fronk (1985b) monitored atrazine levels at water treat-
ment plants, which utilized PAC, in Bowling Green and Tiffin, Ohio.
Applied at dosages ranging from 3.6 to 33 mg/L, the PAC achieved 31
to 91% removal of atrazine, with higher percent removals again
reflecting higher PAC dosages.
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Atrazine September, 1 987
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Harris and Warren (1964) reported that Amber lite IR-120 cation exchange
resin removed atrazine from aqueous solution to less than detectable
levels. Turner and Adams (1968) studied the effect of varying pH on
different cation and an ion exchange resins. At a pH of 7.2, 45%
removal of atrazine was achieved with Dowex® 2 anion exchange resin
and with H2PO4~ as the exchangeable ion species.
Chi an et al. (1975) reported that reverse osmosis, utilizing cellulose
acetate membrane and a cross-linked polyethelenimine (NS-100) membrane,
successfully processed 40% of the test solution, removing 84 and 98%,
respectively, of the atrazine in the solution.
Miltner and Fronk (1985a) studied the oxidation of atrazine with
ozone in both spiked distilled and ground water. Varying doses of
ozone achieved a 70% removal of atrazine in distilled water and 49 to
76% removal of atrazine in ground water.
Kahn et al. (1978) studied the effect of fulvic acid upon the photo-
chemical stability of atrazine to ultraviolet irradiation. A 50%
removal of atrazine was achieved much faster at higher pH conditions
than at lower pH conditions. In the presence of fulvic acids, the
time needed for ultraviolet irradiation to achieve 50% removal was
almost triple the time required to achieve similar removals without
the presence of fulvic acids. Since fulvic acids will be present in
surface waters, ultraviolet irradiation may not be a cost-effective
treatment alternative.
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Atrazine September, 1987
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IX. REFERENCES
Adler, I.D. 1980. A review of the coordinated research effort on the
comparison of test systems for the detection of mutagenic effects,
sponsored by the E.E.C. Mutat. Res. 74:77-93.
Arrington, L.R. 1972. The laboratory animals. In; Introductory laboratory
animal science. The breeding, care and management of experimental animals.
Danville, IL: Interstate Printers and Publishers, Inc., pp. 9-11.
Baker, D. 1983. Herbicide contamination in municipal water supplies in
northwestern Ohio. Final Draft Report 1983. Prepared for Great Lakes
National Program Office, U.S. Environmental Protection Agency. Tiffin, OH»
Bakke, J.E., J.D. Larson and C.E. Price. 1972. Metabolism of atrazine and
2-hydroxyatrazine by the rat. J. Agric. Food Chem. 20:602-607.
Bashmurin, A.F. 1974. Toxicity of atrazine for animals. Sb. Rab. Leningrad
Vet. Institute. 36:5-7. (English abstract only)
Beynon, K.I., G. Stoydin and A.N. Wright. 1972. A comparison of the
breakdown of the triazine herbicides cyanazine, atrazine and simazine
in soils and in maize. Pestic. Biochem. Physiol. 2:153-161.
Bohme, E., and F. Bar. 1967. Uber den Abbau von Triazin-Herbiciden in
tierischen Organismus. Food Cosmet. Toxicol. 5:23-28. (English abstract
only)
Bradway, D.E., and R.F. Moseman. 1982. Determination of urinary residue
levels of the n-dealkyl metabolites of triazine herbicides. J. Agric.
Food Chem. 30:244-247.
Buchanan, G.A., and A.E. Hiltbold. 1973. Performance and persistence of
atrazine. Weed Sci. 21:413-416.
Chian, E.S.K., W.N. Bruce and H.H.P. Fang. 1975. Removal of pesticides by
reverse osmosis. Environmental Science and Technology. 9(1):52-59.
Ciba-Geigy. 1971. Rat reproduction study-test for teratogenic or embryotoxic
effects. 10/1971; Teratology study of atrazine technical in Charles
River rats 9/1984, SCDFA, Sacramento.
Ciba-Geigy. 1983a. Dermal absorption of 14c-atrazine by rats. Ciba-Geigy
Corporation, Greensboro, NC. Report No. ABR-83005, May, 1983. Accession
No. 255815.
Ciba-Geigy. 1983b. Excretion rate of 14c-atrazine from dermally dosed rats.
Ciba-Geigy Corporation, Greensboro, NC. Report No. ABR-83081, October,
1983. Accession No. 255815.
Ciba-Geigy Ltd. 1984a. A teratology study of atrazine technical in Charles
River Rats: Toxicology/pathology report No. 60-84. MRID 00143008.
-------
Atrazine * September, 1987
-18-
Ciba-Geigy Ltd. 1984b. Segment II. Teratology study in rabbits: Toxicology/
pathology report'No. 68-84. MRID 00143006.
Ciba-Geigy. 1985. Atrazine chronic feeding/oncogenicity study. One-year
interim report. May 17, 1985.
Ciba-Geigy. 1987. Briefing paper on atrazine. December, 1986. Analysis of
chronic rat feeding study results. Ciba-Geigy Corp., Greensboro, NC.
Cohen, S.Z., C. Eiden and M.N. Lorher. 1986. Monitoring Ground Water for
Pesticides in the U.S.A. Jn Evaluation of pesticides in ground water.
American Chemical Society Symposium Series, (in press).
Cosmopolitan Laboratories.* 1979. CBI, Document No. 00541, EPA Accession No.
2-41725.
CSE Laboratories.* 1980. CBI, Document No. 000850, EPA Accession No. 2-43485.
Darwent, A.L., and R. Behrens. 1968. Dissipation and leaching of atrazine
in a Minnesota soil after repeated applications. In Proc. North Cent.
Weed Control Conf., December 3-5, 1968, Indiana, pp. 66-68.
Dauterman, W.C., and W. Muecke. 1974. In vitro metabolism of atrazine by
rat liver. Pestic. Biochem. Physiol. 4:212-219.
ESE. 1984. Environmental Science and Engineering. Review of treatability
data for removal of 25 synthetic organic chemicals from drinking water.
U.S. Environmental Protection Agency, Office of Drinking Water, Washington,
DC.
Erickson, M.D., C.W. Frank and D.P. Morgan. 1979. Determination of s-triazine
herbicide residues in urine: Studies of excretion and metabolism in swine
as a model to human metabolism. J. Agric. Food Chem. 27:743-745.
Foster, T.S., S.U. Khan and M.H. Akhtar. 1979. Metabolism of atrazine by
the soluble fraction (105,000 g) from chicken liver homogenates.
J. Agric. Food Chem. 17:300-302.
Frear, E.H., ed. 1969. Pesticide index. State College, PA: College Science
Publications.
Gaines T.B., Linder, R.E. 1986. Acute toxicity of pesticides in adult and
weanling rats. Fundam. Appl. Toxicol. 7:299-308
Goswami, K.P., and R.E. Green. 1971. Microbial degradation of the herbicide
atrazine and its 2-hydroxy analog.
Harris, C.I., and G.F. Warren. 1964. Adsorption and desorption of herbicides
by soil. Weeds. 12:120-126.
Harris, C.I. 1967. Fate of 2-chloro-£-triazine herbicides in soil. J. Agric.
Food Chem. 15:157-162.
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Atrazine September, 1987
-19-
Hayes, W.J.,Jr. 1982. Pesticides studied in man. Baltimore, MD: Williams
and Wilkins.
Hazelton Laboratories.* 1961. Two-year chronic feeding study in rats.
CBI, Document No. 000525, MRID 00059211.
Helling, C.S. 1971. Pesticide mobility in soils. II. Applications of soil
thin-layer chromatography. Proc. Soil Sci. Soc. Am. 35:737-748.
Hurle, K., and E. Kibler. 1976. The effect of changing moisture conditions
on the degradation of atrazine in soil. Proceedings of the British Crop
Protection Conference—Weeds. 2:627-633.
Innes, J.R.M., B.M. Ulland, and M.G. Valerio. 1969. Bioassay of pesticides
and industrial chemicals for tumorigenicity in mice: A preliminary note.
J. Natl. Cancer Inst. 42:1101-1114.
Ivey, H.J., and H. Andrews. 1964. Leaching of simazine, atrazine, diuron,
and DCPA in soil columns. Unpublished study submitted by Ciba-Geigy,
Greensboro, N.C.
Ivey, M.J., and H. Andrews. 1965. Leaching of simazine, atrazine, diruon,
and DCPA in soil columns. Unpublished study prepared by University of
Tennessee, submitted by American Carbonyl, Inc., Tenafly, NJ.
Khan, S.U., and T.S. Foster. 1976. Residues of atrazine (2-chloro-4-ethyl-
amino-6-isopropylamino-s-triazine) and its metabolites in chicken tissues.
J. Agric. Food Chera. 24:768-771.
Khan, S.U., and M. Schnitzer. 1978. "UV irradiation of atrazine in aqueous
fulvic acid solution. Environmental Science and Health. 813:299-310.
Lavy, T.L. 1974. Mobility and deactivation of herbicides in soil-water
systems: Project A-024-NEB. Available from National Technical Information
Service, Springfield, VA; PB-238-632.
Lavy. T.L., F.W. Roeth and C.R. Fenster. 1973. Degradation of 2,4-D and atra-
zine at three soil depths in the field. J. Environ. Qual. 2:132-137.
Lehman, A.J. 1959. Appraisal of the safety of chemicals in foods, drugs and
cosmetics. Assoc. Food and Drug Off.
Loprieno, N., R. Barale, L. Mariani, S. Presciuttini, A.M. Rossi, I. Shrana,
L. Zaccaro, A. Abbondandolo and S. Bonatti. 1980. Results of mutagenicity
tests on the herbicide atrazine. Mutat. Res. 74:250.
Lykins, Jr., B.W., E.E. Geldreich, J.Q. Adams, J.C. Ireland and R.M. Clark.
1984. Granular activated carbon for removing nontrihaloraethane organics
from drinking water. , U.S. Environmental Protection Agency, Office of
Research and Development, Municipal Environmental Research Laboratory,
Cincinnati, OH.
Meister, R.G., ed. 1987. Farm chemicals handbook. 3rd ed. Willoughby, OH:
Meister Publishing Co.
-------
Atrazine September, 1987
-20-
Miltner, R.J., and C.A. Fronk. 1985a. Treatment of synthetic organic contami=
nants for Phase II regulations. Progress report. U.S. Environmental
Protection Agency, Drinking Water Research Division. July 1985.
Miltner, R.J., and C.A. Fronk. 1985b. Treatment of synthetic organic contami-
nants for Phase II regulations. Internal report. U.S. Environmental
Protection Agency, Drinking Water Research Division. December 1985.
Molnar, V. 1971. Symptomatology and pathomorphology of experimental poisoning
with atrazine. Rev. Med. 17:271-274. (English abstract only)
Murnik, M.R., and C.L. Nash. 1977. Mutagenicity of the triazine herbicides
atrazine, cyanazine, and simazine in Drosophila melanogaster. J. Toxicol.
Environ. Health. 3:691-697.
NAS. 1977. National Academy of Sciences. Drinking Water and Health.
Washington, DC: National Academy Press, pp. 533-539.
Newby, L., and B.C. Tweedy. 1976. Atrazine residues in major rivers and
tributaries. Unpublished study submitted by Ciba-Geigy Corporation,
Greensboro, N.C.
Palmer, J.S., and R.D. Radeleff. 1964. The toxicological effects of certain
fungicides and herbicides on sheep and cattle. Ann. N.Y. Acad. Sci.
111:729-736.
Palmer, J.S., and R.D. Radeleff. 1969. The toxicity of some organic herbicides
to cattle, sheep and chickens. Production Research Report No. 1066.
U.S. Department of Agriculture, Agricultural Research Service: 1-26.
Peters, J.W., and R.M. Cook. 1973. Effects of atrazine on reproduction in
rats. Bull. Environ. Con tarn. Toxicol. 9:301-304.
Portnoy, C.E. 1978. Disappearance of bentazon and atrazine in silt loam soil.
Unpublished study submitted by BASF Wyandotte Corporation, Parsippany, NJ.
Schlichter, J.E., and V.B. Beat. 1972. Dermatitis resulting from herbicide
use — A case study. J. Iowa Med. Soc. 62:419-420.
Smith, A.E., R. Grover, G.S. Etnmond and H.C. Korven. 1975. Persistence and
movement of atrazine, bromacil, monuron, and simazine in intermittently-
tilled irrigation ditches. Can. J. Plant Sci. 55:809-816.
STQRET. 1987.
Talbert, R.E., and O.H. Fletchall. 1965. The adsorption of some S-triazines
in soils. Weeds. 13:46-52.
Turner, M.A., and.R.S. Adams, Jr. 1968. The adsorption of atrazine and
atratone by anion- and cation-exchange resins. Soil Sci. Amer. Proc.
32:62-63.
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Atrazine September, 1987
-21-
U.S. EPA. 1986a. U.S. Environmental Protection Agency. Atrazine chronic
feeding/oncogenicity study preliminary incidence table of tumors regarding
possible section 6(a)(2) effect. Washington, DC: U.S. EPA Office of
Pesticide Programs.
U.S. EPA. 1986b. U.S. Environmental Protection Agency. Guideline for
carcinogen risk assessment. Fed. Reg. 51(1 85):33992-34003. September 24.
U.S. EPA. 1986c. U.S. Environmental Protection Agency. Code of Federal
Regulations. Protection of the environment. Tolerances and exemptions
from tolerances for pesticide chemicals in or on raw agricultural commodi-
ties. 40 CFR 180.220. p. 216.
U.S. EPA. 1986d. U.S. Environmental Protection Agency. Method #1 - Determina-
tion of nitrogen and phosphorus containing pesticides in ground water by
GC/NPD. January, 1986 draft.
Warnock , R.E., and J.B. Leary. 1978. Paraquat, atrazine and Bladex—dissipa-
tion in soils. Unpublished study prepared by Chevron Chemical Company,
submitted by Shell Chemical Company, Washington, DC.
Weidner, C.W. 1974. Degradation in groundwater and mobility of herbicides.
Master's thesis. University of Nebraska, Department of Agronomy.
Wolf, D.C., and J.P. Martin. 1975. Microbial decomposition of ring-14c-
atrazine, cyanuric acid, and 2-chloro-4,6-diamino-S-triazine. J. Environ.
Qual. 4:134-139.
Woodard Research Corporation.* 1964. Two-year feeding study in dogs. CBI,
Document No. 000525, MRID 00059213.
Woodard Research Corporation.* 1966. Three-generation reproduction study in
in rats. CBI, Document No. 000525, MRZD 00024471.
Yoder, J., M. Watson and W.W. Benson. 1973. Lymphocyte chromosome analysis
of agricultural workers during extensive occupational exposure to
pesticides. Mutat. Res. 21:335-340.
Windholz, M., ed. 1976. The Merck index. 9th ed. Rahway, NJ: Merck and
Co., Inc.
•Confidential Business Information submitted to the Office of Pesticide
Programs.
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