August, 1987
DIURON
Health Advisory
Office of Drinking Water
U.S. Environmental Protection Agency
I. INTRODUCTION
The Health Advisory (HA) Program, sponsored by the Office of Drinking
Water (ODW), provides information on the health effects, analytical method-
ology and treatment technology that would be useful in dealing with the
contamination of drinking water. Health Advisories describe nonregulatory
concentrations of drinking water contaminants at which adverse health effects
would not be anticipated to occur over specific exposure durations. Health
Advisories contain a margin of safety to protect sensitive members of the
population.
Health Advisories serve as informal technical guidance to assist Federal,
State and local officials responsible for protecting public health when
emergency spills or contamination situations occur. They are not to be
construed as legally enforceable Federal standards. The HAs are subject to
change as new information becomes available.
Health Advisories are developed for one-day, ten-day, longer-term
(approximately 7 years, or 10% of an individual's lifetime) and lifetime
exposures based on data describing noncarcinogenic end points of toxicity.
Health Advisories do not quantitatively incorporate any potential carcinogenic
risk from such exposure. For those substances that are known or probable
human carcinogens, according to the Agency classification scheme (Group A or
B), Lifetime HAs are not recommended. The chemical concentration values for
Group A or B carcinogens are correlated with carcinogenic risk estimates by
employing a cancer potency (unit risk) value together with assumptions for
lifetime exposure and the consumption of drinking water. The cancer unit
risk is usually derived from the linear multistage model with 95% upper
confidence limits. This provides a low-dose estimate of cancer risk to
humans that is considered unlikely to pose a carcinogenic risk in excess
of the stated values. Excess cancer risk estimates may also be calculated
using the one-hit, Weibull, logi't or probit models. There is no current
understanding of the biological mechanisms involved in cancer to suggest that
any one of these models is cible 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. 330-54-1
Structural Formula
N'-(3,40ichlorophenyi)-N,N-dimethylurea
Synonyms
0 Crisuron; Dailon; Di-on; Dichlorfendism; Diurex, Drexel; Duran;
Dynex; DCMU; Herbatox; HW 920; Karmex; Sup'r flo; Telvar, Urox D;
Vonduron (Meister, 1983).
Uses
0 Pre-emergence herbicide (Meister, 1984).
Properties (Meister, 1984; Windholz et al., 1983}
Chemical Formula
Molecular Weight 233.10
Physical State (at 25°C) White crystalline solid
Boiling Point
Melting Point 158-159°C
Vapor Pressure (20°C) 3.1 x 10-6 nun Hg
Specific Gravity —
Water Solubility (25°C) 42 mg/L
Log Octanol/Water Partition —
Coefficient
Taste Threshold
Odor Threshold --
Conversion Factor —
Occurrence
Diuron has been found in none of the 8 surface water samples analyzed
and in 25 of 939 ground water samples (STORET, 1987). Samples were
collected at 6 surface water locations and 930 ground water locations,
and diuron was found only in California and Georgia. The 85th percentile
of all non-zero samples was 1 ug/L in ground water sources only. The
maximum concentration found in ground water was 5 ug/L.
Diuron residues as a result of agricultural practice have been detected
in ground waters in California in wells at low (e.g., 2 to 3 ppb)
levels (California Department of Food and Agriculture, 1986).
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Environmental Fate
0 Radiolabeled diuron and its degradation products 3-(3,4-dichlorophenyl)-
1-methylurea (DCPMU) and 3-(3,4-dichlorophenyl)urea (DCPU) had half-lives
of 4 to 8, 5, and 1 month, respectively, in aerobic soils maintained
at 18 to 29°C and moisture levels at approximately field capacity
(Walker and Roberts, 1978; Elder, 1978). 3,4-Dichloroaniline (DCA)
was identified as a minor degradation product of diuron (Belasco,
1967; Belasco and Pease, 1969; Elder, 1978). Increasing soil organic
matter content appears to increase the rate of decline of diuron
phytotoxic residues (McCormick, 1965; Corbin and Upchurch, 1967;
McCormick and Hiltbold, 1966; Liu et al., 1970).
0 Degradation of diuron phytotoxic residues is much (28 to 50%) slower
in flooded soil than in aerobic soil (Imamliev and Bersonova, 1969;
Wang et al., 1977).
8 Diuron has a low-to-intermediate mobility in fine to coarse-textured
soils and freshwater sediments (Hance 1965a; Hance, 1965b; Harris and
Sheets, 1965; Harris, 1967; Helling and Turner, 1968; Grover and
Hance, 1969; Gerber et al., 1971; Green and Corey, 1971; Helling,
1971; Guth, 1972; Grover, 1975; Helling, 1975). Mobility is correlated
with organic matter content and (CEC). Soil texture apparently is not,
by itself, a major factor governing the mobility of diuron in soil.
0 In a study using radiolabeled material, the diuron degradation products
(96% pure) had K^ values of 66 and 115 in silty clay loam soils,
indicating that they are relatively immobile or less mobile than diuron
(Elder, 1978).
8 In the field, diuron residues (nonspecific method used) generally
persisted for up to 12 months in soils that ranged in texture from sand
to silt loam treated with diuron at 0.8 to 4 Ib/A (Cowart, 1954; Hill
et al., 1955; Weed et al., 1953; Weed et al., 1954; Miller et al.,
1978). These residues may leach in soil to a depth of 120 cm (4 feet).
Diuron was detectable (3 to 74 ppb) in runoff-water sediment and soil
samples for up to 3 years after the last application to pineapple-
sugarcane fields in Hawaii (Mukhtar, 1976; Green et al., 1977).
8 Phytotoxic residues persisted for up to 12 months in soils ranging in
texture from sand to silty clay loam to boggy meadow soil following
the last of one to six annual applications of diuron at 1 to 18 Ib/A
(Weldon and Timmons, 1961; Dalton et al., 1965; Bowmer, 1972; Dawson
et al., 1978; Arle et al., 1965; Wang and Tsay, 1974; Spiridonov et al.,
1972; Addison and Bardsley, 1968; Cowart, 1954; Hill et al., 1955;
Weed et al, 1953; Weed et al., 1954). Diuron persistence in soil
appears to be a function of application rate and amount of rainfall
and/or irrigation water. Three degradation products (DCPMU, DCPU,
and DCA) were identified in soil (planted to cotton) that had received
multiple applications of diuron (80% wettable powder totaling 5 to 5.7
Ib/A (Dalton et al., 1965).
•• Diuron persists in irrigation-canal soils for 6 or more months following
application at 33 to 46 kg/ha (Evans and Duseja, 1973a; Evans and
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Diuron August, 1987
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Duseja, 1973t>; Bowmer and Adeney, 1978a; Bowmer and Adeney,
1978b). The relative percentages of diuron and its degradates DCPMU
and DCPU were 60-90:10-25:1-30 in clay and sandy clay soils, 4.5 to 17
weeks after treatment. Diuron levels in water samples were highest
(0.5 to 8 ppm) in the initial flush of irrigation-water. These levels
declined rapidly, probably as a function of dilution and not degradation,
III. PHARMACOKINETICS
Absorption
0 Diuron is absorbed through the gastrointestinal tract of rats and dogs.
Hodge et al. (1967) fed diuron to rats and dogs at dietary levels
from 25 to 2,500 ppm and from 25 to 1,250 ppm active ingredient (a.i.),
respectively, for periods up to two years. These doses are equivalent
to 1.25 to 125 mg/kg/day for the rat and 0.635 to 31.25 mg/kg/day for
the dog. Urinary and fecal excretion products after one week to 2
years accounted for about 10% of the daily dose ingested. The
excretion data provided evidence that gastrointestinal absorption
ocurred in rats and dogs.
Distribution
0 Hodge et al. (1967) fed diuron (80% wettable powder) for 2 years
to rats at dietary levels of 25 to 2,500 ppm a.i. and to dogs at
dietary levels of 25 to 1,250 ppm a.i. Assuming that 1 ppm in the
diet is equivalent to 0.05 mg/kg/day in rats and 0.025 mg/kg/day in
dogs, this corresponds to doses of 1.25 to 125 mg/kg/day in rats and
0.625 to 31.25 mg/kg/day in dogs (Lehman, 1959). Analysis of tissue
samples for diuron residues revealed levels ranging from 0.2 to 56 ppm,
depending on dose. This constituted only a minute fraction of
the total dose ingested. The authors concluded that there was little
diuron storage in tissues.
Metabolism
0 Geldmacher von Mallinckrodt and Schlussier (1971) analyzed the urine
of a woman who had ingested a dose cf 38 mg/kg of diuron along with
20 mg/kg of aminotriazole. The urine was found to contain
1-(3,4-dichlorophenyl)-3-methylurea and 1 -(3,4-dichlorophenyl)-urea,
and may also have contained some 3,4-dichloroaniline. No unaltered
diuron was detected.
0 Hodge et al. (1967) fed diuron (80% wettable powder) to male beagle
dogs at a dietary level of 125 ppm active ingredient for 2 years.
Assuming that 1 ppm in the diet is equivalent to 0.025 mg/kg/day
(Lehman, 1959), this corresponds to a dose of 3.1 mg/kg/day. Analysis
of urine at weeks one to four or after two years revealed the major
metabolite was N-(3,4-dichlorophenyl)-urea. Small amounts of
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N-(3,4-dichlorophenyl)-N'-methylurea, 3,4-dichloroanaline,
3,4-dichlorophenol and unmetabolized diuron also were detected.
Excretion
0 Hodge et al. (1967) fed diuron (80% wettable powder) for 2 years
to rats at dietary levels of 25 to 2,500 ppm and to dogs at dietary
levels of 25 to 1,250 ppm. Assuming that 1 ppm in the diet is equivalent
to 0.05 mg/kg/day in rats and 0.025 mg/kg/day in dogs, this corresponds
to doses of 1.25 to 125 mg/kg/day in rats and 0.625 to 31.25 mg/kg/day
in dogs (Lehman, 1959). In rats, urinary excretion (6.3 to 492 ppm,
depending on dose) was consistently greater than fecal excretion
(1.0 to 204 ppm). In dogs, urinary excretion (6.3 to 307 ppm) was
similar to fecal excretion (7.9 to 308 ppm). For both rats and dogs,
combined urinary and fecal excretion accounted for only about 10% of
the daily diuron ingestion.
IV. HEALTH EFFECTS
Humans
No information was found in the available literature on the health
effects of diuron in humans.
Animals
Short-term Exposure
0 Acute oral LD50 values of 1,017 mg/kg and 3,750 mg/kg have been
reported in albino rats by Boyd and Krupa (1970), NIOSH (1985) and
Taylor (1976a), respectively. Signs of central nervous system
depression were noted after treatment.
0 Hodge et al. (1967) administered single oral doses of recrystallized
diuron in peanut oil to male CR rats. The approximate lethal dose was
5,000 mg/kg, and the LDgg was 3,400 mg/kg. Survivors sacrificed after
14 days showed large and dark-colored spleens with numerous foci of
blood formation.
0 Hodge et al. (1967) administered oral doses of 1,000 mg/kg of
recrystallized diuron five times a week for 2 weeks (10 doses) to
six male CR rats. At necropsy, 3 or 11 days after the final dose,
the spleens were large, dark and congested, and foci of blood formations
were noted in both the spleen and bone marrow.
0 Hodge et al. (1967) fed Wistar rats (five/sex/dose) diuron (purity
not specified) in the diet for 42 days at dose levels of 0, 200, 400,
2,000, 4,000 or 8,000 ppm a.i. Assuming that 1 ppm in the diet is
equivalent to 0.05 mg/kg/day (Lehman, 1959), this corresponds to
doses of 0, 10, 20, 100, 200 or 400 mg/kg/day. Following treatment
body weight, clinical chemistry, food consumption, hematology,
urinalysis and histology were evaluated. No effects were observed at
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400 ppm (20 mg/kg/day) or less. At 2,000 ppm (100 mg/kg/day) or
greater, red blood cell counts and hemoglobin values were decreased.
A marked inhibition of growth occurred in the 4,000 ppm (200 mg/kg/day)
or greater dosage groups, and there was increased mortality at 8,000
ppm. Based on these data, a No-Observed-Adverse-Effect-Level (NOAEL)
of 400 ppm (20 mg/kg/day) and a Lowest-Observed-Adverse-Effect-Level
(LOAEL) of 2,000 ppm (100 mg/kg/day) were identified.
Dermal/Ocular Effects
0 Taylor (1976b) applied diuron (98% pure) to the intact or abraded skin
of eight albino rabbits at dose levels of 1,000 to 2,500 rag/kg for 24
hours. After treatment, a slight erythema was observed, but no other
symptoms of toxicity were noted during a 14-day observation period.
The dermal LD5Q was reported as >2,500 mg/kg.
0 Larson (1976) applied diuron (98% pure) at doses of 1, 2.5, 5 or 10
n»9/kg to intact abraded skin of rabbits for 24 hours. Adverse effects
were not detected in exposed animals.
0 In studies conducted by DuPont (no date), diuron (50% water paste)
was not irritating to intact skin and was moderately irritating to
abraded skin of guinea pigs. No data were available on skin
sensitization. See also DuPont (1961).
0 In studies conducted by Larson and Schaefer (1976), 10 mg of a fine
dry powder of diuron (98% a.i.) was instilled into the conjunctival
sac of one eye of each of six New Zealand White rabbits. Ocular
irritation was not detected within 72 hours.
Long-term Exposure
0 Hodge et al. (1967) fed albino Charles River rats (five/sex/dose)
diuron (98%"pure) for 90 days at dietary levels of 0, 50, 500 or
5,000 ppm. Assuming that 1 ppm in the diet is equivalent to 0.05
ing/kg/day (Lehman, 1959), this corresponds to doses of 0, 2.5, 25 or
250 mg/kg/day. Following treatment, body weight, food consumption,
clinical chemistry and histopathology were evaluated. No adverse
effects were observed in any parameter at 50 ppm. At 500 ppm there
were no effects on males, but females gained less weight than controls
and appeared cyanotic. At the 5,000-ppm dose level, body weights
were reduced in both sexes, spleens were enlarged and exhibited
hemosiderosis, and there was clinical and pathological evidence of
chronic methemoglobinemia. Based on these data, a NOAEL of 50 ppm
(2.5 mg/kg/day) and a LOAEL of 500 ppm (25 mg/kg/day) were identified.
0 Hodge et al. (1967) fed diuron (80% wettable powder) to groups of
Charles River rats (20/sex/dose) for 90 days at dietary levels of 0,
250 or 2,500 ppm active ingredient. Assuming that 1 ppm in the diet
is equivalent to 0.05 mg/kg/day (Lehman, 1959), this corresponds to
doses of 0, 12.5 or 125 mg/kg/day. At 2,500 ppm, both males and
females ate less and gained less weight did than controls. There was
a slight decrease in red blood cell count, greater in females than in
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males. No effect on food consumption or weight gaiir was noted at
250 ppm, but hematological changes were evident in females. This
study identified a LOAEL of 250 ppm (12.5 mg/kg/day), the lowest
dose tested.
8 In a 2-year feeding study conducted by Hodge et al. (1964a, 1967),
beagle dogs (two males/dose and three females/dose) were administered
technical diuron (80% a.i.) in the diet at dose levels of 0, 25, 125,
250 or 1,250 ppm active ingredient. Assuming that 1 ppm in the diet
of dogs is equivalent to 0.025 mg/kg/day (Lehman, 1959), this corresponds
to doses of diuron of 0, 0.625, 3.12, 6.25 or 31.25 mg/kg/day.
Following treatment, body weight, clinical chemistry, hematology,
organ weight, gross pathology and histopathology were evaluated. No
adverse effects were reported at 25 ppm in any parameter measured.
Abnormal blood pigment was observed at 125 ppm or greater. ,Hemato-
logical alterations (depressed red blood cells (RBC), hematocrit and
hemoglobin) were observed at 250 ppm or greater. In the 1,250 ppm
group, a slight weight loss occurred as well as increased erythrogenic
activity in bone marrow and hemosiderosis of the spleen. Based on
these data, a NOAEL of 25 ppm (0.625 mg/kg/day) and a LOAEL of 125 ppm
(3.12 mg/kg/day) were identified.
0 Hodge et al. (1964b, 1967) administered technical diuron (80% a.i.)
in the diet of rats (35/sex/dose) for 2 years at dose levels of 0,
25, 125, 250 or 2,500 ppm active ingredient. Assuming that 1 ppm in
the diet of rats is equivalent to 0.05 mg/kg/day (Lehman, 1959), this
corresponds to doses of diuron of 0, 1.25, 6.25, 12.5 or 125 mg/kg/day.
Following treatment, body weight, clinical chemistry, hematology,
food consumption, urinalysis, organ weights and histopathology were
evaluated. No adverse effects were reported at 25 ppm (1.25 mg/kg/day)
for any parameters measured. Abnormal blood pigments (sulfhemoglobin)
were observed at 125 ppm (6.25 mg/kg/day) or greater. Hematological
changes (decreased RBC, reduced hemoglobin), growth depression,
hemosiderosis of the spleen and increased mortality were observed at
250 ppm (12.5 mg/kg/day) or greater. Based on these data, a NOAEL of
25 ppm (1.25 mg/kg/day) and a LOAEL of 125 ppm (6.25 mg/kg/day) were
identified.
Reproductive Effects
0 Hodge et al. (1964b, 1967) studied the effects of diuron (80% wet-
table powder) in a three-generation reproductio'n study in rats.
Animals were supplied food containing 125 ppm active ingredient.
Assuming that 1 ppm in the diet of rats is equivalent to 0.05 mg/kg/
day (Lehman, 1959), this corresponds to a dose of 6.25 mg/kg/day.
Fertility rate, body weight, hematology and histopathology were
monitored. No effect was seen on any parameter except body weight,
which significantly decreased in the F2D and F3a litters. A LOAEL
of 125 ppm (6.25 mg/kg/day) was identified.
Developmental Effects
0 Khera et al. (1979) administered by gavage a formulation containing
80% diuron at dose levels of 125, 250 or 500- mg/kg of formulation to
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Diuron August, 1987
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pregnant Wistar rats (14 to 18/dose) on days 6 through 15 of gestation.
Vehicle (corn oil) controls (19 dams) were run concurrently. No
maternal or teratogenic effects were observed at 125 mg/kg/day.
Developmental effects appeared to increase in all treatment groups,
i.eo wavy ribs, extra ribs and delayed ossification. The incidence
of wavy ribs was statistically significant at 250 mg/kg and greater.
Maternal and fetal body weights decreased significantly at 500 mg/kg
(p <0.05). A NOAEL was not determined from this study for fetotoxic
effects; hence, a LOAEL of 125 mg/kg of formulation per day was
identified.
Mutagenicity
0 Andersen et al. (1972) reported that diuron did not exhibit mutagenic
activity in T4 bacteriophage test systems (100 ug/plate) or in tests
with eight histidine-requiring mutants of Salmonella typhimurium
(small crystals applied directly to surface of plate).
0 Fahrig (1974) reported that diuron (purity not specified) was not
mutagenic in a liquid holding test for mitotic gene conversion in
Saccharomyces cerevisiae, in a liquid holding test for forward mutation
to streptomycin resistance in Escherichia coli, in a spot test for
back mutation in £. marcescens or in a spot test for forward mutation
in _E. coli.
0 Recent studies by DuPont (1985) did not detect evidence of mutagenic
activity for diuron in reversion tests in several strains of £.
typhimurium (with or without metabolic activation), in a Chinese
hamster ovary/hypoxanthine guanine phosphoribosyl-transferase (CHO/HGPRT)
forward gene mutation test or in unscheduled DNA synthesis tests in
primary rat hepatocytes. However, in an in vivo cytogenetic test in
rats, diuron was observed to cause clastogenic effects.
Carcinogenicity
0 Hodge et al. (1964b, 1967) fed Wistar rats (35/sex/dose) diuron (80%
wettable powder) in the diet at levels of 0, 25, 125, 250 or 2,500 ppm
a.i. for 2 years. Assuming that 1 ppm in the diet of rats corresponds
to 0.05 mg/kg/day (Lehman, 1959), this corresponds to doses of 0,
1.25, 12.5 or 125 mg/kg/day. There was some early mortality in males
at 250 and 2,500 ppm, but the authors ascribed this to viral infection.
Histological examination of tissues showed no evidence of changes
related to diuron; however, only 10 animals or fewer were examined
per group. Tumors and neoplastic changes observed were similar in
exposed and control groups, and the authors concluded there was no
evidence that diuron was carcinogenic in rats.
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
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Diuron August, 1987
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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)
where:
NOAEL or LOAEL = No- or Lowest-Observed-Adverse-Effect-Level
in mg/kg bw/day.
BW = assumed body weight of a child (10 kg) or
an adult (70 kg).
UF = uncertainty factor (10, 100 or 1,000), in
accordance with NAS/ODW guidelines.
____ L/day = assumed daily water consumption of a child
(1 L/day) or an adult (2 L/day).
One-day Health Advisory
No suitable information was found in the available literature for use in the
determination of the One-day HA value for diuron. It is, therefore, recommended
that the Ten-day HA value for a. 10-kg child, calculated below as 1.0 mg/L
(1,000 ug/L) be used at this time as a conservative estimate of the One-day
HA value.
Ten-day Health Advisory
The study by Khera et al. (1979) has been selected to serve as the
basis for the Ten-day HA for diuron. In this study, pregnant rats were
administered diuron (80%) on days 6 through 15 of gestation at dose levels
of 125, 250 or 500 mg/kg/day. Developmental effects appeared to increase in
the diuron-treated groups as compared to the control group, i.e. wavy ribs,
extra ribs and delayed ossification. The incidence of wavy ribs was
statistically significant at 250 mg/kg/day (p <0.05). Fetal and maternal
body weights were decreased at 500 mg/kg (p <0.05). A NOAEL was not determined
from this study at the lowest dose tested (LOT) based on developmental toxicity;
hence, the LOAEL for this study was 125 mg/kg/day (LOT).
Using a LOAEL of 125 ma/kg/day, the Ten-day HA for a 10-kg child is
calculated as follows:
Ten-Day HA ^ (125 mg/kg/day) (10 kg) (0.80) . uo /L (1 000 ug/L)
(1,000) (1 L/day)
where:
125 mg/kg/day = LOAEL, based on fetotoxicity in rats exposed to
diuron via the diet for days 6 through 15 of gestation.
10 kg = assumed body weight of a child.
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0.80 = correction factor to account for 80% active ingredientc
1,000 = uncertainty factor, chosen in accordance with NAS/ODW
guidelines for use with a LOAEL from an animal study.
1 L/day = assumed daily water consumption of a child.
Longer-term Health Advisory
The 90-day feeding study in rats by Hodge et al. (1967) has been chosen
to serve as the basis for determination of the Longer-term HA values for diuron,
In this study, five animals per sex were fed diuron (98% pure) at dose levels
of 0, 2.5, 25 or 250 mg/kg/day. Based on decreased weight gain and
methemoglobinemia, this study identified a NOAEL of 2.5 mg/kg/day and a LOAEL
of 25 mg/kg/day. These values are supported by the 42-day feeding study of
Hodge et al. (1964b), in which a NOAEL of 20 mg/kg/day and a LOAEL of 100
mg/kg/day were identified. This study was not selected, however, since the
duration of exposure was only 42 days.
Using a NOAEL of 2.5 mg/kg/day, the Longer-term HA for a 10-kg child
is calculated as follows:
Longer-term HA - (2'5 mg/kg/day) (10 kg) = 0.25 mg/L (250 ug/L)
(100) (1 L/day)
where:
2.5 mg/kg/day = NOAEL, based on absence of effects on weight gain or
blood chemistry in rats exposed to diuron via the
diet for 90 days.
10 kg = assumed body weight of a child.
100 = uncertainty factor, chosen in accordance with NAS/ODW
guidelines for use with a NOAEL from an animal study.
1 L/day = assumed daily water consumption of a child.
The Longer-term HA for a 70-kg adult is calculated as follows:
Lon<:er-term HA = (2.5 mg/kg/day) (70 kg) = 0.875 mg/L (875 ug/L)
(100) (2 L/day)
where:
2.5 mg/kg/day = NOAEL, based on absence of effects on weight gain or
blood chemistry in rats exposed to diuron via the
diet for 90 days.
70 kg = assumed body weight of an adult.
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Diuron August, 1987
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100 = uncertainty factor, chosen in accordance with NAS/ODW
guidelines for use with a NOAEL from an animal study.
2 L/day = assumed daily water consumption of an adult.
Lifetime Health Advisory
The Lifetime HA represents that portion of an individual's total exposure
that is attributed to drinking water and is considered protective of noncar-
cinogenic adverse health effects over a lifetime exposure. The Lifetime HA
is derived in a three-step process. Step 1 determines the Reference Dose
(RfD), formerly called the Acceptable Daily Intake (ADI). The RfD is an esti-
mate of a daily exposure to the human population that is likely to be without
appreciable risk of deleterious effects over a lifetime, and is derived from
the NOAEL (or LOAEL), identified from a chronic (or subchronic) study, divided
by an uncertainty factor(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 2-year feeding study in dogs by Hodge et al. (1964a, 1967) has been
selected to serve as the basis for the Lifetime HA for diuron. In this
study, dogs (three/sex/dose) were fed diuron at doses of 0.625, 3.12, 6.25 or
31.15 mg/kg/day of active ingredient. Hematological alterations were observed
at 3.12 mg/kg/day or greater, and this was identified as the LOAEL. No effects
were reported at 0.625 mg/kg/day in any parameter measured, and this was
identified as the NOAEL. This value is supported by a lifetime study in rats
by the same authors (Hodge et al., 1964b). In this study, rats were fed
diuron at dose levels of 0, 1.25, 6.25, 12.5 or 125 mg/kg/day for 2 years.
Hematological changes were observed at 6.25 mg/kg/day or greater, and a NOAEL
of 1.25 mg/kg/day was identified.
Using a NOAEL of 0.625 mg/kg/day, the Lifetime HA is calculated as
follows:
Step 1: Determination of the Reference Dose (RfD)
RfD = (0.625 mq/kg/day) = 0<002 mg/kg/day
(100) (3) y y
where:
0.625 mg/kg/day = NOAEL, based on absence of hematological effects in
dogs exposed to diuron via the diet for 2 years.
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Diuron August, 1987
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100 = uncertainty factor chosen in accordance with NAS/ODW
guidelines for use with a NOAEL from an animal study.
3 = additional uncertainty factor used in the Office of
Pesticide Programs (U.S. EPA, 1987). This factor
is used to account for a lack of adequate chronic
toxicity studies in the data base preventing estab-
lishment of the most sensitive toxicological end
point.
Step 2: Determination of the Drinking Water Equivalent Level (DWEL)
DWEL = (0*002 mg/kg/day) (70 kg) = 0.07 mg/L (70 ug/L)
(2 L/day)
where:
0.002 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 = (0.07 mg/L) (20%) = 0.014 mg/L (14 ug/L)
where:
0.07 mg/L = DWEL.
20% = assumed relative source contribution from water.
Evaluation of Carcinogenic Potential
0 Hodge et al. (1964b, 1967) fed rats (35/sex/dose) diuron in the diet
at ingested doses of up to 125 mg/kg/day for 2 years. Histological
examinations did not reveal increased frequency of tumors; however,
fewer than half of the survivors were examined.
0 The International Agency for Research on Cancer has not evaluated the
carcinogenic potential of diuron.
0 Applying the criteria described in EPA's guidelines for assessment
of carcinogenic risk (U.S. EPA, 1986a), diuron may be classified in
Group D: not classified. This category is for substances with
inadequate animal evidence of carcinogenic!ty.
0 Structurally related analogue(s) (e.g., linuron) of diuron appears to
reflect some oncogenic activity. In addition, a Russian study by
Rubenchik et. al. (1973) reported gastric carcinomas and pancreatic
adenomas in rats (strain not designated) given 450 mg/kg/ day for
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Diuron August, 1987
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22 months. However, the actual data for the study is unavailable
for Agency review.
VI. OTHER CRITERIA, GUIDANCE AND STANDARDS
0 An Acceptable Daily Intake (ADI) of 0.002 mg/kg/day, based on a
NOAEL of 0.625 mg/kg from a dog study and an uncertainty factor of
300 has been calculated (U.S. EPA, I986b).
0 Residue tolerances have been established for diuron in or on agricul-
tural commodities that range from 0.1 to 7 ppm (U.S. EPA, 1985).
VII. ANALYTICAL METHODS
0 Analysis of diuron is by a high-performance liquid chromatographic
(HPLC) method applicable to the determination of certain carbaraate
and urea pesticides in water samples (U.S. EPA, 1986c). This method
requires a solvent extraction of approximately 1 L of sample with
methylene chloride using a separatory funnel. The methylene chloride
extract is dried and concentrated to a volume of 10 mL or less. HPLC
is used to permit the separation of compounds, and measurement is
conducted with an ultraviolet (UV) detector. The method detection
limit has not been determined for diuron, but it is estimated that the
detection limits for analytes included in this method are in the
range of 1 to 5 ug/L.
VIII. TREATMENT TECHNOLOGIES
0 Available data indicate that granular-activated carbon (GAC) and
powdered activated carbon (PAC) adsorption and chlorination effectively
remove diuron from water.
0 El-Dib and Aly (1977b) determined experimentally the Freundlich
constants for diuron on GAC. Although the values do not suggest a
strong adsorption affinity for activated carbon, diuron is better
adsorbed than other phenylurea pesticides.
0 El-Dib and Aly (1977b) calculated, based on laboratory tests, that
66 mg/L of PAC would be required to reduce diuron concentration by
98%, and 12 mg/L of PAC to reduce diuron concentration by 90%.
8 Conventional water treatment techniques of coagulation with ferric
sulfate, sedimentation and filtration proved to be only 20% effective
in removing diuron from contaminated water (El-Dib and Aly, 1977a).
Aluminum sulfate was reportedly less effective than ferric sulfate.
•»
0 Oxidation with chlorine for 30 minutes removed 70% of diuron at a pH 7.
Under the same conditions, 80% of diuron was oxidized by "chlorine
dioxide (EL-Dib and Aly, 1977a). Chlorination, however, will produce
several degradation products whose.environmental toxic impact should
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Diuron August, 1987
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be evaluated prior to selection of oxidative chlorination for treatment
of diuron-contaminated water.
The treatment technologies cited above for the removal of diuron from
water are available and have been reported to be effective. However,
selection of individual or combinations of technologies to attempt
diuron removal from water must be based on a case-by-case technical
evaluation and an assessment of the economics involved.
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Diuron August, 1987
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IX. REFERENCES
Addison, D.A., and C.E. Bardsley. 1968. Chlorella vulgaris assay of the
activity of soil herbicides. Weed Sci. 16:427-429.
Andersen, K.J., E.G. Leighty and M.T. Takahasi. 1972. Evaluation of herbi-
cides for possible mutagenic properties. J. Agr. Food Chem. 20:649-656.
Arle, H.F., J.H. Miller and T.J. Sheets. 1965. Disappearance of herbicides
from irrigated soils. Weeds. 13(1):56-60.
Belasco, I.J. 1967. Absence of tetrachloroazobenzene in soils treated with
diuron and linuron. Unpublished study submitted by E.I. du Pont de
Nemours & Company, Inc., Wilmington, OE.
*
Belasco, I.J., and H.L. Pease. 1969. Investigation of diuron- and linuron-
treated soils for 3, 3*,4,4'-tetrachloroazobenzene. J. Agric. Food
Chem. 17:1414-1417.
Bowmer, K.H. 1972. Measurement of residues of diuron and simazine in an
orchard soil. Aust. J. Exp. Agric. Anim. Husb. 12(58):535-539.
Bowmer, K.H., and J.A. Adeney. 1978a. Residues of diuron and phytotoxic
degradation products in aquatic situations. I. Analytical methods for
soil and water. Pestic. Sci. 9(4):342-353.
Bowmer, K.H,, and J.A. Adeney. I978b. Residues of diuron and phytotoxic
degradation products in aquatic situations. II. Oiuron in irrigation
water. Pestic. Sci. 9(4):354-364.
Boyd, E.M. and V. Krupa. 1970. Protein deficient diet and diuron toxicity.
J. Agric. Food Chem., 18:1104-1107.
Corbin, F.T., and R.P. Upchurch. 1967. Influence of pH on detoxication of
herbicides in soil. Weeds. 15(4):370-377.
Cowart, L.E. 1954. Soil-herbicidal relationships of 3-(£-chlorophenyl)-
1,1-dimethylurea and 3-(3,4-dichlorophenyl)-l,l-dimethylurea. In
Proceedings of the Western Weed Control Conference. Vol. 14.
Salt Lake City, UT: Western Weed Control Conference, pp. 37-45.
Dalton, R.L., A.W. Evans and R.C. Rhodes. 1965. Disappearance of diuron in
cotton field soils. In Proceedings of the Southern Weed Conference.
Vol. 18. Athens, GA: Southern Weed Science Society, pp. 72-78.
Dawson, J.H., V.G. Bruns and W.J. Clore. 1968. Residual monuron, diuron,
and simazine in a vineyard soil. Weed Sci. 16(1):63-65.
DuPont.* 1961. E. I. du Pont de Nemours & Co., Inc. Condensed technical
information (Diuron).
DuPont.* No date. E. I. du Pont de Nemours & Co., Inc. Toxicity of
3-(3,4-dichlorophenyl)-1,1-dimethylurea. Medical Research Project Nos.
. MR-48 and MR-263. Unpublished study. MRID 00022036.
-------
Diuron August, 1987
-16-
DuPont.* 1985. E. I. du Pont de Nemours & Co., Inc. Mutagenicity studies
with diuron. Salmonella test, No. HLR 471-84 (7185); CHO/HGPRT forward
gene mutation assay, HR No. 282-85 (06/28/85); Unscheduled DMA synthesis
test in primary rat hepatocytes, HLR No. 349-85 (07/10/85); and in vivo
cytogenetic test. No. 36685 (06/20/85).
Elder, V.A. 1978. Degradation of specifically labeled diuron in soil and
availability of its residues to oats. Doctoral dissertation. Honolulu,
HI: University of Hawaii. Available from: University Microfilms,
Ann Arbor, MI. Report No. 79-13776.
El-Dib, M.A., and O.A. Aly 1977a. Removal of phenylamide pesticides from
drinking waters. I. Effect of chemical coagulation and oxidants.
Water Res. 11:611-616.
El-Dib, M.A., and O.A. Aly. 1977b. Removal of phenylamide pesticides from
drinking waters. II. Adsorption on powdered carbon. Water Res.
11:617-620.
Evans, J.O., and D.R. Duseja. I973a. Herbicide contamination of surface
runoff waters. Washington, DC: U.S. Environmental Protection Agency,
Office of Research and Monitoring. EPA-R2-73-266; available from National
Technical Information Service, Springfield, VA. PB-222283.
Evans, J.O., and D.R. Duseja. 1973b. Results and discussion: Field experi-
ments. In Herbicide contamination of surface runoff waters. Utah State
University, pp. 33-35, 38-43. EPA-R2-73-266; project no. 13030 FDJ;
available from Superintendent of Documents, U.S. Government Printing
Office, Washington, DC.
Fahrig, R. 1974. Comparative mutagenicity studies with pesticides.
International Agency for Research on Cancer (IARC), Lyon, France.
Sci. Pub. 10. pp. 161-181.
Geldmacher von Mallinckrodt, M., and F. Schlussier.* 1971. Metabolism and
toxicity of 1-(3,4-dichlorophenyl)-3,3-dimethylurea (diuron) in man.
Arch. Toxicol. 27(3):311-314. Cited in Weed Abst. 21:331.
MRID 00028010.
Gerber, H.R., P. Ziegler and P. Dubah. 1971. Leaching as a tool in the
evaluation of herbicides. In Proceedings of the 10th British Weed
Control Conference (1970).. Vol. 1. Droitwich, England: British Weed
Control Conference, pp. 118-125.
Green, R.E., and J.C. Corey. 1971. Pesticide adsorption measurement by flow
equilibration and subsequent displacement. Proc. Soil Sci. Soc. Am.
35:561-565.
Green, R.E., K.P. Goswami, M. Mukhtar and H. Y. Young. 1977. Herbicides
from cropped watersheds in stream and estuarine sediments in Hawaii.
J. Environ. Qual. 6(2):145-154.
Grover, R. 1975. Adsorption and desorption of urea herbicides on soils.
Can. J. Soil Sci. 55:127-135.
-------
Diuron August, 1987
-17-
Grover, R., and R.J. Hance. 1969. Adsorption of some herbicides by soil and
roots. Can. J. Plant Sci. 40:378-380.
Guth, J.A. 1972. Adsorption and leaching characteristics of pesticides in
soil. Unpublished study including German test, prepared by Ciba-Geigy,
AG, submitted by Shell Chemical Company, Washington, DC.
Hance, R.J. I965a. Observations on the relationsip between the adsorption
of diuron and the nature of the adsorbent._ Weed Res. 5:108-114.
Hance, R.J. I965b. The adsorption of urea and some of its derivatives by a
variety of soils. Weed Res. 5:98-107.
Harris, C.I. 1967. Movement of herbicides in soil. Weeds. 15(3}:214-216.
Harris, C.I., and T.J. Sheets. 1965. Influence of soil properties on
adsorption and phytotoxicity of CIPC, diuron, and simazine. Weeds.
13(3):215-219.
Helling, C.S. 1971. Pesticide mobility in soils: II. Applications of soil
thin-layer chromatography. Proc. Soil Sci. Soc. Am. 35:737-748.
Helling, C.S. 1975. Soil mobility of three Thompson-Hayward pesticides.
Interim Report. U.S. Agricultural Research Service, Pesticide Degradation
Laboratory; unpublished study.
Helling, C.S., and B.C. Turner. 1968. Pesticide mobility: Determination by
soil thin-layer chromatography. Method dated Nov. 1, 1968. Science.
162:562-563.
Hill, G.D., J.W. McGahen, H.M. Baker, D.W. Finnerty and C.W. Bingeman. 1955.
The fate of substituted urea herbicides in agricultural soils. Agron. J.
47(2):93-104.
Hodge, H.C., W.L. Downs, E.A. Maynard et al.* 1964a. Chronic feeding studies
of diuron in dogs. Unpublished study. MRID 00017763.
Hodge, H.C., W.L. Downs, E.A. Maynard et al.* 1964b. .Chronic feeding studies
of diuron in rats. Unpublished study. MRID 00017764.
Hodge, H.C., W.L. Downs, B.S. Panner, D.W. Smith and E.A. Maynard. 1967.
Oral toxicity and metabolism of diuron (N-(3,4 )-dichlorophenyl)-N',N'-
dimethylurea) in rats and dogs. Food Cosmet. Toxicol. 5:513-531.
Imamliev, A.I., and K.A. Bersonova. 1969. Movement of detoxication of dalapon
and diuron in soil. In Problems of physiology and biochemistry of the
cotton plant. A.I. Imamliev and E.A. Popova, eds. Tashkent, USSR:
Akademii Nauk Uzbekskoi, Institut Eksperimental'noi Biologii Rastenii.
pp. 266-274.
Khera, K.S., C. Whalen, G. Trivett and G. Angers. 1979. Teratogenicity
studies on pesticidal formulations of dimethoate, diuron and lindane in
rats. Bull. Environ. Contain. Toxicol. 22:522-529.
-------
Diuron August, 1987
-18-
Larson, K.A.* 1976. Acute dermal toxicity—Diuron. Unpublished study.
MRID 00017795.
Larson, K.A., and J.H. Schaefer.* 1976. Eye irritation study using the
pesticide diuron. For Colorado International Corporation. Unpublished
study. MRID 00017797.
Lehman, A.J. 1959. Appraisal of the safety of chemicals in foods, drugs and
cosmetics. Assoc. Food Drug Off. U.S.
Liu, L.C., H.R. Cibes-Viade and J. Gonzalez-Ibanez. 1970. The persistence
of atrazine, ametryne, prometryne, and diuron in soils under greenhouse
conditions. J. Agric. Univ. Puerto Rico. 54(4):631-639.
McCormick, L.L. 1965. Microbiological decomposition of atrazine and diuron
in soil. Doctoral dissertation. Auburn, AL: Auburn University.
Available from: University Microfilms, Ann Arbor, MI. Report No. 65-6892.
McCormick, L.L., and A.E. Hiltbold. 1966. Microbiological decomposition of
atrazine and diuron in soil. Weeds. 14(1):77-82.
Meister, R., ed. 1984. Farm chemicals handbook. Willoughby, OH: Meister
Publishing Company, p. C85.
Miller, J.H., P.E. Keeley, R.J. Thullen and C.H. Carter. 1978. Persistence
and movement of ten herbicides in soil. Weed Sci. 26(1):20-27.
Mukhtar, M. 1976. Desorption of adsorbed ametryn and diuron from soils and
soil components in relation to rates, mechanisms, and energy of adsorption
reactions. Doctoral dissertation. Honolulu, HI: University of Hawaii.
Available from University Microfilms, Ann Arbor, MI. Report No. 77-14,601.
NIOSH. 1985. National Institute for Occupational Safety and Health.
Registry of Toxic Effects of Chemical Substances (RTECS). National
Library of Medicine Online File.
Rubenik, B.L., N.E. Botsman, G.P. Gorman and L.I. Loevskaya. 1973.
Relation between the chemical structure and carcinogenic activity
of urea derivatives. Oukalogiya (Kiev) 4:10-16.
Spiridoncv, Y.Y., V.s. Skhiladze and G.S. Spiridonova. 1972. The effects ->f
diuron and monuron in a meadow-bog soil of the moist subtropics of
Adzhariia. Subtrop. Crops. (1):150-155.
STORET. 1987.
Taylor, R.E.* 1976a. Acute oral toxicity (LD50). Project TlOOl. Unpublished
study. MRID 00028006.
Taylor, R.E.* 1976b. Primary skin irritation study. Project T1002.
Unpublished study. MRID 00028007.
U.S. EPA. 1985. U.S. Environmental Protection Agency. Code of Federal
Regulations. 40 CFR 180.106, p. 252. July 1, 1985.
-------
Diuron August, 1987
-19-
U.S. EPA. 1986a. U.S. Environmental Protection Agency. Guidelines for
carcinogen risk assessment. Fed. Reg. 51(185):33992-34003. Septem-
ber 24. .
U.S. EPA. I986b. U.S. Environmental Protection Agency. Acceptable Daily
Intake Data; Tolerances Printout, February 21. Office of Pesticide
Programs. Office of Pesticides and Toxic Substances.
U.S. EPA. 1986c. U.S. Environmental Protection Agency. U.S. EPA Method #4
- Determination of Pesticides in Ground Water by HPLC/UV, January 1986
draft. Available from U.S. EPA's Environmental Monitoring and Support
Laboratory, Cincinnati, OH.
U.S. EPA. 1987. U.S. Environmental Protection Agency. Interim guidance for
establishing Rfd dated May 1, 1987 as an addendum to TOX SOP #1002.
Office of Pesticide Programs.
Walker, A., and M.G. Roberts. 1978. The degradation of methazole in soil.
II. Studies with methazole, methazole degradation products, and diuron.
Pestic. Sci. 9(4):333-341.
Wang, C.C., and J.S. Tsay. 1974. Accumulative residual effect and toxicity
of some persistence herbicides in multiple cropping areas. Med. Coll.
Med. Natl. Taiwan Univ. 14(1):1-13.
Wang, Y.S., T.C. Wang and Y.L. Chen. 1977. A study on the degradation of
herbicide diuron in soils and under the light. J. Chinese Agric. Chem.
Soc. 15(1/2):23-31.
Weed, M.B., R. Sutton, G.D. Hill and L.E. Cowart. 1953. Substituted ureas
for pre-emergence weed control in cotton. Unpublished study submitted
by E.I. du Pont de Nemours & Co. Inc., Wilmington, DE.
Weed, M.B., A.W. Welch, R. Sutton and G.D. Hill. 1954. Substituted ureas
for pre-emergence weed control in cotton. _Iii Proceedings of the Southern
Weed Conference. Vol. 7. Athens, GA: Southern Weed Science Society.
pp. 68-87.
Weldon, L.W., and F.L. Timmons. '1961. Penetration and persistence of diuron
in soil. Weeds. 9(2):195-203.
Windholz, M., S. Budavari, R.F. Blumetti and E.S. Otterbein, eds. 1983. The
Merck Index—an encyclopedia of chemicals and drugs, 10th ed. Rahway, NJ:
Merck and Company, inc.
•Confidential Business Information submitted to the Office of Pesticide
Programs.
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