United SttMi OTOoi of PWfeida *nd Toife Sub«aM«
Envtronmonal PfOtMtton Offie* of PojiwM* PreffrMV (TS-7MCI
t. oc ao«n
v>ERV Pesticide
Fact Sheet
540/FS-92-175
Name of Chemical: prodiamine
Reason for Issuance: Registration
Date Issued: 2/7/92
Fact Sheet Number 231 _.
1. DESCRIPTION OF CHhMICAL
Generic Name: j*3,N3-Di-n-propyl-2,4-dinitro-b-
(trifluoroittethyl)-m-phenylenediamine
Common Maine: Prodiamine
Trade Names: Barricade"
EPA Shaughnessy Code: 110201
Chemical Abstracts Service (CAS) Number: 29091-21-2
Year of Initial Registration: 1991
Pesticide Type: Herbicide
Chemical Family: Dinitro-aniline
U.S. Producer: Sandoz Crop Protection Corporation
2. USE PATTERNS AND FORMULATIONS
Application sites: Terrestrial non-food sites.
Preemergence for selective control of annual grasses
and broadleaf weeas in established lawns and
in landscape ornamentals.
Types of formulations: The two end-use products
are water disperseable granular formulations of the active
ingredient; with a nominal concentration of 65.u%
of the active ingredient. One product is packaged
in water soluble bags to reduce applicator exposure
associated with handling and applying the product.
Amount and Method of Application: Application rates
for 2-6 months control of weeds varies between
0.325 and 1.5 Ibs. of active ingredient per acre,
depending on the weeds to be controlled. Maximum
annual application rates varies between 0.5 and
1.5 Ibs. of active ingredient per acre, per season;
depending on the species of turf grass. Ground
spray application of aqueous suspensions of the
formulated product is the only method of application
registered.
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Carrier: Water
3. SCIENCE FINDINGS
Summary Science Statements:
Adequate toxicological, product chemistry, ecological
effects, environmental fate and ground water
data have been submitted and reviewed to support the
conditional registration of prodiamine for use as a
preemergence herbicide in the culture of ornamental turf
grasses and landscape ornamentals. Technical prodiamine
is classified as a Toxicity Category III pesticide and is
labeled with the signal word "CAUTION", based on a battery
of 6 acute studies.
Studies demonstrated that prodiamine generally
has a negative mutagenic activity. However, there
was a suggestive activity in Salmonella strain TA 1538
without activation (Registrant claimed that material
tested was from an outdated manufacturing process)
and in mouse lymphoma cells without activation, but neg-
ative in confirmatory testing. Prodiamine was not a develop-
mental toxicant. In a rat teratology study the developmental
toxicity NOEL was 300 mg/kg and the LEL was 1,000 ing/kg
based on the total number of fetuses/litter with malform-
ations. The maternal toxicity NOEL was 300 mg/kg and the
LEL was 1,000 mg/kg based on depressed body weight gain.
In a rabbit teratology study there was no evidence of develop-
mental toxicity at 500 mg/kg/day the highest dose tested (HDT).
A two gereration reproduction study in rats demonstrated
a reproductive toxicity NOEL of 200 ppm based on reduced pup
weight and increased relative liver weight at 2000 ppm.
In a rat carcinogenicity study prodiamine at 3200 ppm in
the diet increased thyroid follicular cell neoplasia in
in both sexes. Positive dose-trends in thyroid follicular
cell adenomas and in combined follicular cell tumors
(adenomas and carcinomas) in both males and females
were observed. In addition, a statistically signific-
ant positive trend in incidence of pancreatic adenomas
was observed in female rats; although the dose trend for
the incidence of carcinomoas and adenomas (combined) was
not significant.
In a mouse carcinogenicity study with prodiamine there
was found an increase in subcutaneous fibrosarcomas in high
level male mice related to fighting.
Based on a "weight-of-evidence" analysis, prodiamine
was determined to be a Group C carcinogen. EPA health Effects
Division's Peer Review Committee recommended that a
Reference Dose Approach should be used for quantification
of risk to humans.
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Prodiamine appears to be metabolized rapidly by
dealkylation reactions to N,N-didespropyl metabolites.
Cyclization also occurs to form N-propyl benzimidazole
A and N-propyl benzimidazole B found in feces. The
N-propyl benzimidazoles were metabolized further via
nitro-reciuction, N-dealkylation, and ring hydroxylation
to form hydroxy-benzimidazoles found in urine.
Acute toxicology studies with technical prodiamine
and the two end-use products containing 65.0% active
prodiamine demonstrated that prodiamine is of low
acute toxicity to mammals.
A 13-week subchronic feeding study in rats demon-
strated that the lowest effect level in rats was 4000 ppm,
The effect was reduced body weight gain, increased
cholesterol and increased urinary protein content.
Prodiamine is very water-insoluble and is not
hydrolyzable. Absorption, leaching and run-off studies
indicate that movement in soil is unlikely. Volatility
is not significant. Prodiamine is stable to hydro-
lysis and moderately bound to sediment. Data demonstrate
that prodiamine is rapidly degraded in water exposed
to natural sunlignt.
An avian single dose oral LD$Q study with bobwhite
quail demonstrated that prodiamine is accutely non-toxic
to boowhite quail. The no-observed-effect dosage was
> 2250 mg/kg/day. In eight day dietary studies with
mallard duck and bobwhite quail the 1*050 level was
> 10,000 mg/kg/day, the highest concentration fed.
Prodiamine is not expected to pose a significant
acute hazard to freshwater organisms at its limit of
solubility in water (13 ppb).
Chemical analysis of both the manufacturing-use
and the end-use products demonstrated that nitrosoamine
would not be expected to be present in these products
at levels of toxicological concern.
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Chemical Characteristics:
Physical State: Solid, powered
Color: Chemically Pure: Yellow-orange
Technical tirade: Yellow-orange
Odor: Halide odor
helting Point: 122.5-124.O'C
Density: 1.4107 gin/ml (typical)
holecular Weight 350.3
Empirical Formula
Solubility Solvent
Parts per Million: Water
Grams per 100 ml: Acetone
n-octanol
Dimethyl
foriuamide
Xylene
Isopropanol
Heptane
0.013
at *C
25' C
22.600
0.962
32.100
3.540
0.852
0.100
25'
25*
20'
20'
20*
20'
C
C
C
C
C
C
Vapor Pressure:
Dissociation Constant:
2.5 x 10~8 mm/Hg at 25*C
Data waived because of low
water solubility.
Octanol/Water Partition Coefficient: P * 1.3 x 104
pH: (in non-aqueous solvent): 6.878 at 25*C
Stability: Thermally stable. Moderately stable to
light. Decomposes at 240 C
Oxidizing or Reducing Action: Slight oxidizing potential
Explodability: Non-explosive
Storage Stability: Stable for 84 days at 54"c and
168 days at 40 , and 1 year at
ambient temperature
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Toxicology Characteristics:
Acute Toxicity ( 93.0%, Technical)
Acute oral toxicity in rats: LD^Q > 5000 rag/kg
Toxicity Category IV.
Acute dermal toxicity (rat): LD$Q > 2,000 mg/kg (M&F)
Toxicity Category III.
Primary dermal irritation (rabbit)i Non-irritating to
skin of rabbits
Toxicity Category IV.
Primary eye irritation (rabbit): No cornea1 opacity;
minimally irritating to eyes of rabbits
Toxicity Category III.
Acute inhalation toxicity (rat): LC50 > 0.256 mg/m3 for
males and females
Toxicity Category III.
Dermal sensitization (guinea pig): Not a dermal
sensitizer.
Acute Toxicity for Barracade* 65 WDG Herbicide
Acute oral toxicity (rats): L&5Q > 5000 mg/kg (h&F)
Toxicity Category IV.
Acute dermal toxicity (rats): No deaths, LI>5o
>2000 mg/Kg, Category III.
Primary dermal irritation (rabbit): Very slight erytheme
in 1 of 6 rabbits
Category IV.
Primary eye irritation (rabbit): 5/6 rabbits had conjunctival
redness and chemosis > score 1, but reaction
vanished by 4th day.
Category III.
Acute inhalation toxicity (rat): LCso > l.til mg/L (M&F)
Category III.
Dermal sensitization (guinea pig): Positive for dermal
sensitization.
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Subchronic and Chronic Toxicity
A 13-week feeding study with rats demonstrated
a no observed effect level (NOEL) of 1200 ppm; a
least effect level (LEL) of 4000 ppm. The observed
effects seen in both male and females were a reduction
of body weight gain and increased cholesterol value.
Increased urinary protein content was seen only in
males.
/
In a rat developmental toxicity study developmental
effects (increased incidence of omphalocele) were
observed only at 300 mg/kg (LEL). The NOEL for this
developmental effect was 100 mg/kg. A maternal
effect (depressed body weight gains) was also observed at
at 1000 mg/kg (LEL). The NOEL for this effect was 300 mg/kg.
In a rabbit developmental toxicity study there were no develop-
mental effects at 500 mg/kg/day (hDT). A maternal effect
(reduced body weight gain) was observed at 300 mg/kg (LEL)
The NOEL for this effect was 100 mg/kg/day.
A 2-generation reproduction study in the rat treated with
0, 50, 200, and 2,000 ppm prodiamine had a NOEL of 200 ppm
(approximately 10 mg/Kg/day) based on reduced pup
weight and increased relative liver weight at 2,000 ppm.
Mutagenicity
The following mutagenicity studies indicated that
prodiamine is not generally mutagenic at doses tested:
- Ames Assays for mutagenicity with TA1538 strain of
Salmonella were found positive for increased revert-
ants in TA1538 at 5000 ug/plate in the absence of activation.
The registrant states that the material tested was from
an outdated manufacturing process.
- Ames Assays for mutagenicity with five tester
strains of Salmonella were negative for reverse gene mutation
(his" to his'1') at 10,000 ug/plate with or without
metabolic activation up to 10,000 ug/plate with
precipitation at 500 ug/plate and above.
- Ames Assays for mutagenicity with Salmonella was negative
at 0.3 - 100 vig/plate with or without metabolic activation.
- A mutagenic-unscheduled DNA synthesis study demonstrated
that prodiamine was non-matagenic.
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hechanism of Pesticidal Action;
Prodiamine is a mitotic inhibitor of normal cell
division of susceptible plants. The formation and
function of microtubulin is inhibited. Susceptible plant
roots are stunted and fail to function in the presence
of prodiamine. Plants do not grow and develop through
their normal cycle of vegetative growth followed by
reproduction (flowering and seed setting;. Susceptible
plants react to prodiamine in such a way as to be
less competitive.
Environmental Characteristics:
Hydrolysis: Prodiamine slowly hydrolyzes in the
pH range of 5-9. Mo significant degradation
occurs after 30 days. A hydrolysis study conducted
at pH 5, 1 and 9 indicated that degradation by
hydrolysis is greater than 6 months.
Photodegradation: The half-life of prodiamine is
20 minutes in deionized water and 40 minutes
in natural water.
Aerobic Soil Metabolism: The anerobic
breakdown of prodiamine in soil is considerably
more rapid than aerobic breakdown. Different
metabolites were observed for these conditions
of metabolism. The bound residue level was higher
under anaerooic conditions. Prodiamine had a
half-life of 3^ days under anerobic conditions
and 218 days under aerobic conditions. The half-life
of prodiamine under aerobic soil conditions is
approximately 2 months. The major soil degradate is
6-amino-benzimidazole under aerobic soil conditions.
Leaching: Prodiamine or its degradates do not
leach significantly. Under field conditions
prodiamine is immobile with regard to downward
movement in soil.
Runoff: Runoff of prodiamine is unlikely to occur
because of its insolubility and immobility.
Soil Adsorption/ Desorption: Prodiamine is very
strongly adsorbed to soil, more strongly than
dinitramine. Data demonstrate that prodiamine is
extremely immobile.
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- Mouse lynphoma foreward nutation assay with or without
metabolic activation at concentrations of 0.5,
1, 4, 6, 8, 10, 13. 16. 20, and 50 ug/ml with
activation was negative. In a nonactivated study
it was also negative at 1, 10, 40, 60, 80, 100,
130, 160, 200 and 500 ug/ng.
A 2-year feeding/oncogenic mouse study demonstrated
a significant increased incidence of subcutaneous fibro-
sarcoma in high dose Bales was related to fighting activity
caused by group caging. Levels tested were 0, 50, 500,
and 5000 ppm (Ms 0, 6.2, 59.4 and 606.6 ug/kg/day; F:
0, 6.8, 64.6 and 646.2 mg/kg/day). Systemic effects
(reduced body weight gains and increased liver weight)
were observed at 5000 ppm (LEL). The NOEL for this
effect was 500 ppm.
A 2-year feeding/oncogenic rat study demonstrated
a significant increased incidence of follicular adenoma/
carcinoma in both males and females. Levels tested were
0, 50, 200, 800 and 3200 ppm (M: 0, 1.8, 7.2 29.4, and
115.2 mg/kg/day; Ft 0, 2.3 9.1, 37 and 151 mg/kg/day).
Systemic effects (increased liver weight and minor bio-
chemical disturbances) occurred at 800 ppm (LEL). The
NOEL for this effect was 200 ppm.
In a metabolism study with rats, prodiamine was absorbed
and readily eliminated after a single dose of 10 or 400
mg/kg of C^4-prodiamine or a single oral dose of 10 ing/kg
of the radioactive compound following 14 days of admin-
istration of 10 mg unlabeled prodiamine/kg/day. All but
high-dose female rats had eliminated about 70% of the
C1* dose in the urine and feces within 24 hour (high-dose
females excreted about 38% of the dose). Tissue radio-
activity levels were slightly higher in females than
those in males. C14 prodiamine and its metabolites did not
accumulate in the body to an appreciable extent.
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4. Summary of Regulatory Postion and Rationale
Available data provide adequate information to support
the conditional registration of Barricade® T Herbicide,
Barricade 65 WG Herbicide, and Barricade 65 WG Herbicide
in Water Soluble Packs, that were first conditionally
registered February 7, 1992 under Section 3 of the Federal
Insecticide, Fungicide and Rodenticide Act as amended.
Use, Formulation, Manufacturing Process or
Geographic Restrictions:
o Aerial applications of prodiamine products are not permitted.
Probition against aerial applications must appear on labeling.
o End-use products must bear the following precautions:
"May cause an allergic skin reaction. Wash thoroughly
with soap and water after handling."
"During mixing and loading wear chemical
resistant gloves. Wash non-disposable gloves
thoroughly with soap and water before removing.
Remove contaminated clothing and separately launder
clothing before use.
Conditional registration will expire on February 1, 1995.
5. Summary of Data Requirements
Toxicology Data:
1. Acute and 90-day neurotoxicity screening Battery
in rats (EPA Guideline Numbers 81-S and 82-7) .
Data are due February 1, 1994.
3. Study in rats to measure effects on TSH, T3
and 14.
Data are due April 1, 1993.
Exposure Data:
1. Worker Exposure Studies. Reserved pending review
of required toxicology data listed above.
2. Reentry data: Subpart K (Foliar Dissipation (132-1),
Soil Dissipation (132-2), Dermal Exposure (132-3),
and Inhalation Exposure (132-4)). Reserved pending
review of required toxicology data listed above.
Ecological Effects Data:
1. Avian Reproduction with a Waterfowl and Bobwhite
guail, EPA Ref. Guidelines 71-4. Data are due
May 1, 1994.
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Potential to Contaminate Ground Water: The low solubility
in water and its high tendency to bind to soil
prevents prodiamine from being carried downward
through soil. Prodiamine has a low potential for
leaching into ground water. Surface water con-
tamination from soil containing prodiamine would
be expected.
Ecological Characteristics
Avian Studies: Prodiamine is practically non-toxic
to birds based on the following studies:
Single Dose Acute Oral LD50:
Bobwhite Quail with 96.3% Technical:
> 2250 mg/Kg
Eight Day Dietary Study:
Mallard duck with 98.4 Technical:
LCso > 10,000 ppm
Bobwhite quail with 98.4% Technical:
> 10,000 ppm
A study is required as a condition
Avian Reproduction:
for registration.
Aquatic Organisms: The following data indicate that
prodiamine is not toxic to freshwater fish and
aquatic invertebrates:
Fish Acute Toxicity:
Bluegill sunfish,
Rainbow trout,
> 552.0 ppb
> 829.0 ppb
Freshwater Invertebrates:
A 48-hour ECso in Daphnia was > 658 ppb
Honey Bee:
Acute contact LDso > 10° ug/bee.
Endangered Species Hazards:
Based on available data, the conditionally registered
use-pattern of prodiamine is unlikely to pose a hazard to
endangered aquatic and avian species. There may
be some hazard to endangered plant species from
runoff and movement of the products from treated turf
areas .
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2. Acute LC5Q Estuarine/Marine Organisms Studies,
EPA Ref. Guidelines 72-3, identified as:
o 96-hour LCso for an estuarine marine fish
o 96-hour LCso for a shrimp species
o Either a 48-hour embryo larvae study or a
96-hour shell deposition study with oyster.
Data are due February 1, 1993.
3. Fish Early Life Stage and Aquatic Invertebrate Life-
Cycle Studies, EPA Ref. Guidelines 72-4.
Data are due May 1, 1993.
4. Target Area: Phytotoxicity (if end-use product is
aerially applied).
Tier II: o Seed Germination/Seedling Emergence,
10 species, EPA Ref. Guideline 123-1
o Vegetative vigor, 10 species, EPA Ref. Guideline
123-1
o Aquatic plant growth (5 species), EPA Ref. Guide-
lines 123-2
Tier III: o Terrestrial Field1, EPA Ref. Guidelines
124-1
o Aquatic field2, EPA Ref. Guidelines 124-2
I/ Required if a 25 percent or greater
detrimental effect was found in 1 or more
plant species in corresponding test of
previous tier.
2/ Required if a 25 percent or greater
detrimental effect was found on any
plant species in the corresponding test
of the previous tier.
Data are due at the time of application to amend
any registration of prodiamine to allow aerial
application.
Environmental Fate and Ground Water Data:
1. Prodiamine Aged-Leaching Study, EPA Ref. Guide-
lines 163-1. Data are due June 31, 1992.
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6. Contact Person at £PA
Joanne I. iniller
Product Manager 23
Fungiciae-Herbiciae Branch
Registation Division (H-7505CJ
Office of Pesticide Programs
Environmental Protection Agency
401 M Street SW
Washington, DC 204oO
Office Location and Telephone Number
Room 237, Crystal Mall Building 12
1921 Jefferson Davis Highway
Arlington, VA 22202
(703) 305-7630
DISCLAIMER: The information presented in this Pesticide Fact
Sheet is for informational purposes only and may not be used
to fulfill data requirements for pesticide registration and
reregistration.
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