United States                     Office of Prevention, Pesticides
                   Environmental Protection            and Toxic Substances
                   Agency                          (7501C)
                  Pesticide
                  Fact Sheet
                   Name of Chemical: Clodinafop-propargyl
                   Reason for Issuance: Conditional Registration
                   Date Issued: June 6, 2000
1.     DESCRIPTION OF CHEMICAL

      Generic Name:            Propanoic acid, 2-[4-[(5-chloro-3-fluoro-2-
                               pyridinyl)oxy]phenoxy]-,2-propynyl ester, (2R)-

      Common Name:           Clodinafop-propargyl

      Trade Name:              Discoverô Herbicide

      EPA Shaughnessy Code:    125203

      Chemical Abstracts
      Service (CAS) Number:     105512-06-9

      Year of Initial
      Registration:              2000

      Pesticide Type:            Herbicide

      Chemical Family:          Oxyphenoxy acid ester

      U.S. Producer:            Novartis Crop Protection, Inc.

2.     USE PATTERNS AND FORMULATIONS

      Application Sites:          Clodinafop-propargyl is registered for use on spring wheat.

      Types of Formulations:     97.5% technical product
                               22.3% end use product (Discoverô Herbicide)

      Types and Methods
      of Application:            Ground application using standard commercial sprayers in
                               5 to 10 gals, of water per acre.;  Aerial application in a
                               minimum of 3 gals, of water per acre.

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                                          -2-
       Application Rates:
                           Use rates on spring wheat range from 3.2 to 4.0 ounces of
                           formulated product (0.05 to 0.0625 pounds of active
                           ingredient, clodinafop-propargyl) per acre; applied with
                           10.2 to 12.8 ounces of DSV Adjuvant (sold with
                           Discoverô Herbicide) per acre. A single  application is
                           made to spring wheat from the 2-leaf stage to emergence of
                           the 4th tiller.
       Carrier:
                           Water
3.
SCIENCE FINDINGS
Summary Science Statements

Clodinafop-propargyl is a member of the Oxyphenoxy acid ester chemical class, which includes
the active ingredients fluazifop-butyl, fenoxaprop-ethyl, diclofop methyl, quizalofop-ethyl and
haloxyfop-methyl.  The review of available product chemistry, environmental fate, toxicology,
ecological effects and residue chemistry data for clodinafop-propargyl have been completed.
The data and estimated risks to human health and the environment from its use on spring wheat
are summarized below:
Chemical Characteristics
PROPERTY
Physical State
Color
Odor
Melting Point
Density
Solubility (Water)
Vapor Pressure
Octanol/Water Partition
Coefficient
PH
TECHNICAL
fine powder
cream
odorless
48.2-57.1C
1.37g/cm3@22C
4.0 ppm (a), pH 7, 25C
2.3 9 x 10-8mmHg@25C
logPow =3.90@25C
4.1 @25C
END-USE
liquid
N/A
N/A
N/A
1.076g/mL
N/A
N/A
N/A
4 to 6

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                                          -J-
Toxicology Characteristics
ACUTE TOXICITY (CLODINAFOP-PROPARGYL TECHNICAL)
GDLN
81-1
81-2
81-3
81-4
81-5
81-6
Study Type
Acute Oral- Rat
Acute Dermal -Rat,
Rabbit
Acute Inhalation-
Rat
Primary Eye Irritation-
Rabbit
Primary Skin Irritation-
Rabbit
Dermal Sensitization-
Rat
Results
LD50 =1392 mg/kg (males)
2271 mg/kg (females)
LD50 >2000 mg/kg
LC50 >2.3 mg/L (males or
females)
Slightly eye irritant
Non-irritant
Skin sensitizer
Tox. Cat.
3
3
4
3
4
Skin sensitizer
ACUTE TOXICITY (END USE PRODUCT: DISCOVERô HERBICIDE)
GDLN
81-1
81-2
81-3
81-4
81-5
81-6
Study Type
Acute Oral- Rat
Acute Dermal -Rat
Acute Inhalation-
Rat
Primary Eye Irritation-
Rabbit
Primary Skin Irritation-
Rabbit
Dermal Sensitization-
Guinea Pig
Results
LD50 =223 1 mg/kg (males)
2240 mg/kg (females)
LD,0 >4000 mg/kg
LC50 >3.5 mg/L (males or
females)
Slightly eye irritant
Severe dermal irritant
Skin sensitizer
Tox. Cat.
3
4
4
3
2
Skin sensitizer

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                                              -4-
        SUBCHRONIC AND CHRONIC TOXICITY: CLODINAFOP-PROPARGYL
  Guideline No./
   Study Type
                                   Results
870.31007
28-Day Oral
Gavage in Rats
NOAEL < 5 mg/kg
LOAEL = 5 mg/kg for M and F based on liver toxicity (enzyme changes),
870.31007
13 Week Oral
Toxicity in Rodent
NOAEL = M: 0.9 mg/kg; F: 8.2 mg/kg/day
LOAEL = M: 120 ppm (8.2 mg/kg/day); F: 1000 ppm (71.1 mg/kg/day) decreased
body weight; based on increased liver weights and enzymes (AlPtase); decreased
thymus weight (atrophy). Reversed after 28 day recovery period.
870.31007
13 Week Oral
Toxicity in Mice
NOAEL = M: 0.9mg/kg/day; F: 1.1 mg/kg/day
LOAEL = M: 7.3 mg/kg/day ; F: 8.6 mg/kg/day based on clinical chemistry; glucose,
sodium, and chloride increases and hepatocellular hypertrophy in males and females.
870.3150
90-Day Oral
Toxicity in Dogs
NOAEL = M: 0.346 mg/kg/day, F: 1.89 mg/kg/day.
LOAEL = M: 1.73 mg/kg/day ; F: 7.16 mg/kg/day based on occurrence of skin lesions.
870.3200
28-Day Dermal
Toxicity in Rats.
Systemic NOAEL = 50 mg/kg/day
Systemic LOAEL = 200 mg/kg based on dose-related increases in liver weights and
clinical signs (piloerection and hunched posture) in male rats.
Dermal  NOAEL = 1000 mg/kg/day.
870.3700a
Prenatal
Developmental
Toxicity in Rats
Maternal NOAEL = 160 mg/kg/day
Maternal LOAEL > 160 mg/kg/day based on
 lack of effect.
Developmental NOAEL = 5 mg/kg/day
Developmental LOAEL = 40 mg/kg/day based on increased incidences of bilateral
distension and torsion of the ureters, unilateral 14th ribs, and incomplete ossification of
the metacarpals and various cranial bones (parietals, interparietals, occipital, and
squamosal).
870.3700b
Prenatal
Developmental
Toxicity in Rabbits
Maternal NOAEL = 25 mg/kg/day
Maternal LOAEL = 125  mg/kg/day based on mortality, clinical signs and body weight
loss
Developmental NOAEL = 125 mg/kg/day
Developmental LOAEL >125  mg/kg/day

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                                                -5-
  Guideline No./
    Study Type
                                    Results
870.3800
Two Generation
Rat Reproduction
Study
Parental/Systemic NOAEL= 3.2 mg/kg/day.
Parental/Systemic LOAEL = 31.7 mg/kg/day based on decrease in body weight gain,
reduced food consumption, increased liver and kidney weights and histopathological
changes in the liver and renal tubules.
Offspring NOAEL = 3.2 mg/kg/day
Offspring LOAEL = 31.7 mg/kg/day based on reduced viability, decreased pup body
weight and dilatation of renal pelvis.
Reproductive  NOAEL = 64.2 mg/kg/day.
Reproductive  LOAEL 64.2 mg/kg/day
870.4100b
Chronic Toxicity
Nonrodent
NOAEL = M: 3.38 mg/kg/day; F: 3.37 mg/kg/day
LOAEL = M: 15.2 mg/kg/day ; F: 16.7 mg/kg/day based on occurrence of skin lesions,
clinical signs, and reduced body weight gain and food consumption.
870.4200b
Carcinogenicity
Mice
NOAEL = M: 1.10 mg/kg/day; F: 1.25 mg/kg/day
LOAEL =M: 11.0 mg/kg/day; F: 12.6 mg/kg/day based on increase in liver enzyme
activity and liver weights.
Under the conditions of this study, clodinafop-propargyl induced hepatocellular tumors
at 29.6 mg/kg.  The chemical was tested at doses sufficient to measure its carcinogenic
potential.
870.4300
Chronic/
Oncogenicity in the
Rat.
NOAEL = M:0.03 mg/kg/day ; F: 0.03 mg/kg/day
LOAEL = M: 0.3 mg/kg/day; F: 0.4 mg/kg/day  based on hepatocytic hypertrophy,
chronic progressive nephropathy, and tubular pigmentation.
Under the conditions of this study, treatment with clodinafop-propargyl increased the
incidence of prostate and ovarian tumors in rats at 750 ppm. For males, an increased
incidence of prostate adenoma was seen in the high-dose group.  The chemical was
administered at a dose sufficient to test its carcinogenic potential.
870.5100
Gene Mutation
Salmonella and
Escherichia/Liver
Microsome Test.
Neg. for mutagenicity.
870.5200
Gene Mutation
Mutation Test with
Chinese Hamster
Cells V79
Neg. for mutagenicity.

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                                               -6-
  Guideline No./
    Study Type
                                    Results
870.5315
Chromosome
Studies; Human
Lymphocytes in
vitro.
Owing to the conflicting results from the cytotoxicity assessment and the presence of
rare complex chromosome aberrations both with and without S9 activation, the study is
considered inconclusive.
870.5395
 Micronucleus Test
(Chinese Hamster)
No clear evidence that clodinafop-propargyl induced a clastogenic or aneugenic effect
in either sex at any dose or sacrifice time.
870.5550
DNA Repair
Human Fibroblasts.
Compound precipitation was seen at doses 320 g/mL: there was, however, no
indication of a cytotoxic effect at any dose. The positive control induced the expected
marked increases in UDS.  There was, however, no evidence that CGA-184927 in the
absence of S9 activation induced a genotoxic response in either trial.
870.5550
DNA Repair
Rat Hepatocytes
Compound precipitation was noted at levels  4000 g/mL.  Lethality was apparent in the
preliminary cytotoxicity test at 94.8  g/mL. The positive control induced the expected
marked increases in UDS. There was, however, no evidence that clodinafop-propargyl
induced a genotoxic response in either trial.
870.7485
Metabolism  and
Pharmacokinetics,
The main metabolite was CGA 193469( 76% in male urine). Additional 5% was in the
form of taurine conjugate of CGA 193469. Similar distribution was found in feces.
870.7485
Metabolism  and
Pharmacokinetics,
The major metabolite in urine and feces was determined to be CGA 193469, accounting
for about 36% to 47% of the AD for males, and 80% to 85% of the AD for females. In
addition, 11 minor metabolite fractions were isolated from urine and feces. Three were
further identified as reference materials CGA 193468, CGA 214111 and unchanged
clodinofop-propargyl.
Special Study:
Determination Of
Residues As CGA
193469 In
Abdominal Fat
After A 3-Month
Oral Toxicity Study
In Rat.
There was a dose-dependent increase in clodinofop-propargyl residues in fat samples
from both sexes taken at the end of treatment (14 weeks) and after the 4-week recovery
period (18 weeks). Concentrations of clodinofop-propargyl were higher in male rats at
all dose levels tested.  With the exception of low-dose group males, for all remaining
groups, residues in the fat at 18 weeks had decreased by between 40% - 51.5% of the  14
week value.
Special Study
Determination Of
Residues As CGA
193469 In
Abdominal Fat
After 12 Months In
Study.
1 ppm and 10 ppm, the concentration of CGA 184927 in the abdominal fat was higher
in males when compared to females. At 300 and 750 ppm, the concentration of CGA
184927 in the abdominal fat was comparable between males and females. The results of
this study also indicate that the clodinafop-propargyl residue in fat is reduced after 1
year of treatment compared to 3 month treatment.

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                                                 -7-
  Guideline No./
    Study Type
                                    Results
Special Study: The
Effect Of CGA
184927 On Selected
Biochemical
Parameters In The
Rat Liver
Following
Subchronic
Administration.
The effects of clodinafop-propargyl on selected liver enzymes in the rat were similar to
the effects seen after subchronic treatment with known peroxisome proliferators
(hypolipidemic compounds, phenoxyacetic acid derivatives). Hence, clodinafop-
propargyl was considered to most likely be a peroxisome proliferator in the rat liver.
Special Study:
Apparently Clonal
Thyroid Adenomas
May Contain
Heterogeneously
Growing and
Functioning Cell
Subpopulations.
New Frontiers in
Thyroidology, p.
901-905, 1986
The asynchronous growth rate of subsets of cells within the old adenomas as well as the
intercellular heterogeneity of the endocytotic response to TSH suggests that clonal
thyroid adenomas may acquire new qualities and can modify gene expression via much
debated mechanism. The author concludes that the growth of benign thyroid tumors
and progression does not require a change in genomic expression in any cell. The
apparent heterogeneity of a tumor does not necessarily exclude its monoclonal origin.
Special Study:
Assessment of
Hyperplastic and
Neoplastic Lesions
of the Thyroid
Gland. Tips, Vol.
8, P. 511-514.
 In cell cultures, TSH does not induce proliferation of human thyroid cells, but does
stimulate the growth of cells obtained from rat and dog thyroids. Conventional
procedures of evaluating carcinogenicity tests by simply counting tumors in rodents
treated with high doses, and by mathematical extrapolation to the low doses to which
humans are exposed, are not suitable for the proliferative reactions of the thyroid gland.
In assessing the human risk, relevant conclusions can only be drawn if the physiological
factors of growth control are known, and if the biological mechanisms by which
chemicals initiate focal proliferation and support their progression to tumors are
considered.
Special Study:
Stott, W.t.
Chemically Induced
Proliferation of
Peroxisomes:
Implications for
Risk Assessment.
Regulatory
Toxicology and
Pharmacology, Vol.
8, P. 125-159,
1988.
The author concludes that a more appropriate MTD of a peroxisome proliferative agent
in sensitive species would appear to be based upon evidence of the proliferation of
peroxisomes and the induction of peroxisomal enzymes capable of producing an
increased intracellular oxidative stress. Exceeding these dosages will only result in a
predictable sequence of events leading, ultimately, to tumor formation due to
physiological adaptation of the animal to the administered compound rather than from
the direct effects of the compound itself.

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   Guideline No./
     Study Type
                                  Results
 Special Study
 Bieri, F. The Effect
 of CGA 193469,
 the Free Acid
 Derivative of CGA
 184927,on
 Peroxisomal -
 oxidation in
 Primary Cultures of
 Rat, Mouse,
 Marmoset and
 Guinea Pig
 Hepatocytes.
This study characterized and compared the in vitro effects of clodinafop-propargyl on
selected parameters (i.e., cytotoxicity and induction of peroxisomal beta-oxidation) in
primary hepatocytes from various species.
The monolayer cultures were treated with medium containing clodinafop-propargyl,
CGA 193469 orpropargyl alcohol at the appropriate concentrations (0.1 to 100 ug/mL),
or solvent controls and incubated for three days. Hepatocytes were then examined for
morphological alterations and cell viability.  The lactate dehydrogenase (LDH) activity
was measured as an indicator of cytotoxicity. In addition, protein content of
hepatocytes were measured to determine the membrane damage. Peroxisomal beta-
oxidation was measured in hepatocyte homogenates treated with [l-14]palmitoyl-CoA,
a peroxisomal enzyme marker. Clodinafop-propargyl-induced cytotoxicity through
propargyl alcohol.
 Special Study
 Guyomard, C.
 (1992). Effects of
 Cga-193469, the
 Acid Derivative of
 Cga-184927, on the
 Peroxisomal Beta-
 oxidation in Human
 Hepatocytes.
Under the conditions of this study, neither CGA 193469 nor bezafibric acid induced
peroxisomal beta-oxidation in human hepatocytes, in vitro. However, in the absence of
a known concurrent human positive control to validate the test system, (i.e., a substance
known to elicit peroxisomal beta-oxidation in human hepatocytes,) this cannot be
definitely concluded.
 Special Study:
 Trendelenburg, C.
 Effects on Selected
 Plasma
 Concentrations and
 Biochemical
 Parameters in the
 Liver upon
 Subchronic
 Administration to
 Male Adult Rats.
Clodinafop-propargyl may act as a peroxisomal proliferating agent and alters
monooxygenase activity in subfamilies of cytochrome P450 which are known to be
involved in the synthesis or catabolism of steroid hormones.
Toxicological Endpoints
The dose at which no adverse effects are observed (the NOAEL) from the toxicology study
identified as appropriate for use in risk assessment is used to estimate the toxicological level of
concern (LOG).  The lowest dose at which adverse effects of concern are identified (the
LOAEL) is sometimes used for risk assessment if no NOAEL was achieved in the toxicology
study selected.  An uncertainty factor (UF) is applied to reflect uncertainties inherent in the
extrapolation from laboratory animal data to humans and in the variations in sensitivity among
members of the human population as well as other unknowns.  An UF of 100 is routinely used,
10X to account for interspecies differences and 10X for intra species differences.

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                                          -9-
For dietary risk assessment (other than cancer) the Agency uses the UF to calculate an acute or
chronic reference dose (acute RfD or chronic RfD) where the RfD is equal to the NOAEL
divided by the appropriate UF (RfD=NOAEL/UF). Where an additional safety factor (SF) is
retained due to concerns unique to the Food Quality Protection Act (FQPA), this additional
factor is applied to the RfD by dividing the RfD by such additional factor. The acute or chronic
Population Adjusted Dose (aPAD or cPAD) is a modification of the RfD to accommodate this
type of FQPA Safety Factor.

For non-dietary risk assessments (other than cancer) the UF is used to determine the LOG.  For
example, when 100 is the appropriate UF (10X to account for interspecies differences and 10X
for intraspecies differences) the LOG is 100.  To estimate risk,  a ratio of the NOAEL to
exposures (margin of exposure (MOE) = NOAEL/exposure) is calculated and compared to the
LOG.

The linear default risk methodology (Q*) is the primary method currently used by the Agency to
quantify carcinogenic risk.  The Q*  approach assumes that any amount of exposure will lead to
some degree of cancer risk. A Q* is calculated and used to estimate risk which represents a
probability of occurrence of additional cancer cases (e.g., risk is expressed as
1 x 10"6 or one in a million). Under certain specific circumstances, MOE calculations will be
used for the carcinogenic risk assessment. In this non-linear approach, a "point of departure" is
identified below which carcinogenic effects are not expected. The point of departure is typically
a NOAEL based on an endpoint related to cancer effects though it may be a different value
derived from the dose response curve. To estimate risk, a ratio of the point of departure to
exposure (MOEcancer= point of departure/exposures) is calculated.

The acute and chronic  (non-cancer)  toxicological endpoints that have been established for
clodinafop-propargyl are summarized in the following table.
Exposure
Scenario
Acute Dietary
females 13-50
years of ase

Dose Used in
Risk
Assessment, UF
NOAEL = 5
mg/kg/day
UF = 100
Acute RfD =
0.05 mg/kg/day
FQPA SF* and
Level of Concern
for Risk
Assessment
FQPASF= 10X
aPAD = acute RfD
FQPA SF
= 0.005 mg/kg/day
Study and Toxicological Effects
Developmental Toxicity Study in
Rats]
LOAEL = 40 mg/kg/day based
on increased incidences of
bilateral distension and torsion of
the ureters, unilateral 14th ribs,
and incomplete ossification of
the metacarpals and various
cranial bones (parietals,
interparietals, occipital, and
squamosal)

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                                         -10-
Exposure
Scenario
Acute Dietary
infants and
children

Acute Dietary
general
population

Chronic Dietary
all populations


Dose Used in
Risk
Assessment, UF
NOAEL = 25
mg/kg/day
UF = 100
Acute RfD =
0.25 mg/kg/day
NOAEL = 25
mg/kg/day
UF = 100
Acute RfD =
0.25 mg/kg/day
NOAEL= 0.03
mg/kg/day
UF = 100
Chronic RfD =
0.0003
mg/kg/day
FQPA SF* and
Level of Concern
for Risk
Assessment
FQPA SF = 3X
aPAD = acute RfD
FQPA SF
= 0.083 mg/kg/day
FQPA SF = IX
aPAD = acute RfD
FQPA SF
= 0.25 mg/kg/day
FQPASF= 10X
cPAD =
chronic RfD
FQPA SF
= 0.00003
mg/kg/day
Study and Toxicological Effects
Developmental Toxicity Study in
Rabbits
LOAEL = 125 mg/kg/day based
on increased mortality, clinical
signs and body weight loss
Developmental Toxicity Study in
Rabbits
LOAEL = 125 mg/kg/day based
on increased mortality, clinical
signs and body weight loss
Chronic Toxicity Study in Rats
LOAEL = 0.3 mg/kg/day based
on hepatocytic hypertrophy,
chronic progressive nephropathy,
and tubular pigmentation
* The FQPA Safety Factor refers to any additional safety factor retained due to concerns unique
to the FQPA.

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                                         -11-

Carcinogenicity

In accordance with the EPA ProposedEPA Weight-of-the-Evidence Categories, August 1999,
the Agency's Cancer Assessment Review Committee (CARC) classified clodinafop-propargyl as
"likely to be carcinogenic to humans" by the oral route based on the occurrence of prostate
tumors in male rats, ovarian tumors in female rats, and liver tumors in both sexes of mice, as
well as blood vessel tumors in female mice. For the quantification of human cancer risk, the
CARC recommended a linear low-dose extrapolation approach based on the most potent of these
tumor types. This approach is supported by possible genotoxic potential and the lack of
confirmation of the mode of action of clodinafop-propargyl.  The most potent unit risk,
Q^mg/kg/day)"1, of those calculated for clodinafop-propargyl is that for male mouse liver
benign hepatoma and/or carcinoma combined tumor rates at 0.129 (mg/kg/day)"1 in human
equivalents.

Metabolism

In a rat metabolism study, two 14C labeled  variants of clodinofop-propargyl (one labeled on the
2 pyridil carbon and the other uniformly labeled on the phenyl ring, purity >98%) were
administered to groups of male Tif :RAI f (SPF) rats, approximately 7 weeks of age by gavage at
concentrations of 25.2 mg/kg ( [2-14C]pyridil) and 24.6 mg/kg ([U-14C]phenyl).

In the urine, the major metabolite was determined to be (R)-2-[4-(5-chloro-3-fluoro-2-
pyridinyloxy)-phenoxy]-propionic acid, reference material CGA-193469, accounting for 36.7%
to 39.1% of the administered dose (AD). Metabolite fraction U3 hydrolysed to yield  fraction U7
(i.e., CGA-193469), when treated with NaOH or HC1. Unchanged clodinofop-propargyl was not
identified. In the feces, the major metabolite (fraction F*7) corresponded to the urinary
metabolite U7 (CGA  193469), accounting for 15.7% to 16.9% of the AD.  Metabolite fraction
F*8 was determined to be unchanged clodinofop-propargyl, accounting for 0.4% to 1.7% of the
AD. In the fat, all metabolites were reportedly  acylglycerides, the majority of which were
hybrid di- and triacylglycerides, (i.e., approximately 3.5% and  17.0% of the AD, respectively).

Human Exposures and Risks

Acute Dietary Risk

Using the tolerance for clodinafop-propargyl in/on wheat of 0.1 ppm and assuming that 100% of
the U.S. wheat crop is treated with clodinafop-propargyl, the acute dietary exposure to
Clodinafop-propargyl from food will occupy <1.0% of the aPAD for the U.S. population, 7.5%
of the aPAD for nursing females 13 years and older, the  subgroup of adult females with the
highest estimated exposure, and 1.0% of the aPAD for children 1 to 6 years old, the subgroup of
infants and children with the highest estimated  exposure. In addition, there is potential for acute
dietary exposure to Clodinafop-propargyl in drinking water.  After calculating Drinking Water
Levels of Concern (DWLOCs) and comparing them to the Estimated Environmental

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                                         -12-
Concentrations (EECs) for surface and ground water, EPA does not expect the aggregate
exposure from food and drinking water to exceed 100% of the aPAD.

Aggregate Risk Assessment for Acute Exposure to Clodinafop-propargyl.
Population Subgroup


U.S. Population





Females 13+ years old

Children, 1 to 6 years old

aPAD
(mg/kg)

0.25





0.01

0.083

% aPAD
(Food)

<1.0





7.5

1

Surface
Water EEC
(ppb)
0.23 ppb
clodinafop-
propargyl;
1.1 ppb
CGA-
193469
Same as
above
Same as
above
Ground
Water EEC
(ppb)
5xlO-6ppb
clodinafop-
propargyl;
0.044 ppb
CGA-
193469
Same as
above
Same as
above
Acute
DWLOC
(ppb)
8.7x 103





1.4 x 102

8.3x 102

Chronic Dietary Risk

Using an anticipated residue in wheat of 0.07 ppm (the sum of the limits of quantitation of
clodinafop-propargyl and its acid metabolite, CGA-193469) and assuming that 4% of the U.S.
wheat crop is treated with clodinafop-propargyl, EPA has concluded that exposure to
Clodinafop-propargyl from food will utilize 14 % of the cPAD for the U.S. population and 32%
of the cPAD for children 1 to 6 years old, the subgroup  of infants and children with the highest
estimated exposure. In addition, there is potential for chronic dietary exposure to Clodinafop-
propargyl in drinking water. After calculating DWLOCs and comparing them to the EECs for
surface and ground water, EPA does not expect the aggregate exposure from food and drinking
water to exceed 100% of the cPAD.

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                                          -13-
Aggregate Risk Assessment for Chronic (Non-Cancer) Exposure to Clodinafop-propargyl.
Population
Subgroup

U.S. Population





Children, 1 to 6 years old

cPAD
mg/kg/day

0





0

%
cPAD
(Food)
14





32

Surface
Water EEC
(ppb)
0.0017 ppb
clodinafop-
propargyl;
0.11 ppb
CGA-
193469
Same as
above
Ground
Water EEC
(ppb)
5xlO-6ppb
clodinafop-
propargyl;
0.044 ppb
CGA-
193469
Same as
above
Chronic
DWLOC
(ppb)
0.91





0.21

Dietary Cancer Risk

Assuming residues of 0.07 ppm for wheat and 4% crop treated, EPA estimates that chronic
exposure of the U.S. population to clodinafop-propargyl will be 0.000004 mg/kg/day.  Applying
the Qj* value of 0.129 (mg/kg/day)"1 results in a food only risk of 5.3x 10"7.  Following an
aggregate dietary (food + water) assessment for lifetime cancer risk, the resulting DWLOC is
0.13  g/L or ppb. The largest EEC value is for surface water chronic exposure to the acid
metabolite, CGA-193469 (0.11 ppb). The cancer DWLOC is slightly greater than the highest
EEC.

Because the models used to obtain the EECs for clodinafop-propargyl and CGA-193469 are
highly conservative screening models not designed specifically for estimating concentrations in
drinking water and because of the conversative nature of the food exposure assessment
(anticipated residues at LOQ for parent + metabolite), EPA believes this aggregate cancer
dietary assessment will not underestimate exposure and that chronic dietary exposure from
clodinafop-propargyl residues in food and drinking water will not exceed the Agency's level of
concern for lifetime aggregate cancer risk.

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Environmental Characteristics
STUDY TYPE
Hydrolysis (Half Life)
Photolysis in Water (Half Life)
Photolysis on Soil
Aerobic Soil Metabolism (Half Life)
Aerobic Aquatic Metabolism (Half
Life)
Anaerobic Aquatic Metabolism (Half
Life)
Mobility- Leaching (Parent)
Mobility- Leaching (Metabolite)
Terrestrial Field Dissipation* (Half
T,ifel
HALF LIFE/OTHER
184 days (pH 5)
2.7 days (pH 7)
2.2 hours (pH 9)
N/A
No significant degradation of parent. Minute
photolysis of the acid metabolite (CGA- 193469)
from organic matter.
t-Y2 (parent) = 0.5 to 1.5 days
t-'/2 (CGA-193469) = 33.6 days
N/A
t-1/2 = 513 days
mobile in low organic soil to immobile in high
organic soil
CGA-193469: highly mobile in low to moderate
organic soils
CGA-163469 = less than 5 days in the top 10 cm.
Potential to Contaminate Drinking Water

The likelihood of drinking water contamination by the parent compound, clodinafop-propargyl,
is low due to high sorption and rapid degradation in the environment. However, the major
degradate, CGA-193469, is persistent and highly mobile in low and moderate organic matter
soils and has the potential to contaminate drinking water. The Agency used PRZM/EXAMS and
SCI-GROW models to estimate residues of Clodinafop-propargyl and CGA-193469 in surface
water and ground water and incorporated these estimates into the aggregate risk assessments
discussed above under Human Exposures and Risks

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                                          -15-

Ecological Characteristics/Risk

Terrestrial: Clodinafop-propargyl is practically nontoxic to slightly toxic to birds (LD50 = 1455
mg/kg; LC50 > 5000 ppm), slightly toxic to small mammals (LD50 = 1392 mg/kg) and practically
nontoxic to honey bees (LD50 > 100 ug/bee) on an acute basis. The chronic No Observable
Effects Concentrations (NOECs) for birds and small mammals are 500 amd 50 ppm,
respectively.

Aquatic: Clodinafop-propargyl is highly toxic to freshwater fish and no more than moderately
toxic to freshwater invertebrates (LC50 = 0.30 ppm and EC50 > 2.0 ppm, respectively).  The
primary degradate, CGA-193469, is no more than moderately toxic to freshwater invertebrates
(EC50 > 9.2 ppm).

Plants:  Tier II seedling emergence tests with clodinafop-propargyl indicate that ryegrass (shoot
weight) at 0.031 Ib. ai/Acre is the most sensitive species of all monocot and dicots tested.  For
Tier II vegetative vigor, corn (phytotoxicity) at 0.0048 Ib. ai/Acre is the most sensitive species of
all species tested.  Aquatic plant testing with clodinafop-propargyl indicates that the vascular
plant, Lemna gibba, and the nonvascular plant, Naviculapelliculosa, are the most sensitive
species (EC50 > 2.4 ppm and 3.0 ppm, respectively).

Based on the estimated environmental concentrations (EECs) of clodinafop-propargyl and its
acid metabolite, CGA-193469, the use of Discoverô Herbicide is not expected to pose a risk to
non-target organisms,  with the exception of non-target plants. There is a concern for endangered
terrestrial plants inhabiting dry and semi-aquatic areas adjacent to wheat fields when Discoverô
is applied by air.

Mechanism of Pesticidal Action

Clodinafop-propargyl  interacts with and inhibits the enzyme, acetyl co-enzyme A carboxylase
(ACCase), which is essential for the production of lipids (fatty acids) needed for plant growth.
Selectivity is based on the difference in the speed of herbicide breakdown in the crop versus the
weeds.  Clodinafop-propargyl converts from the ester form to the active  acid and then to
biologically  inactive compounds. Grass weeds such as wild oats and wild millet cannot
effectively break down clodinafop-propargyl, so they are controlled as a lethal dose accumulates
at the meristematic growing points.  A safener, cloquintocet-mexyl, is added to the formulation
to accelerate the rate of clodinafop break down in wheat, thus preventing the accumulation of a
lethal dose.

4.      SUMMARY OF REGULATORY POSITION AND RATIONALE

Available data provide adequate information to  support the conditional registrations of
Clodinafop-propargyl  Technical and Discoverô Herbicide for use on spring wheat.

Use, Formulation, Manufacturing Process or Geographic Restrictions

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                                         -16-

       Restrictions for Use on Spring Wheat:

       1.     For use on spring wheat (including Durum) grown in Montana, Minnesota, North
             Dakota and South Dakota.
       2.     Do not graze livestock or feed forage from treated areas for a minimum of 30
             days following application.
       3.     Do not feed hay for 30 days following application.
       4.     Do not harvest for 60 days following application.
       5.     Make only one appplication per crop season at 3.2 to 4.0 oz. of Discoverô
             Herbicide (0.05 to 0.0625 pounds of active ingredient, clodinafop-propargyl) per
             acre.
       6.     Do not apply through any type of irrigation system.
       7.     Always use DSV Adjuvant (included in the Discoverô case) with Discoverô
             Herbicide

5.      SUMMARY OF DATA GAPS

             Toxicology (Acute, Subchronic and Developmental Neurotoxicity; In vitro
             Cytogenetic Assay)
             Residue Chemistry (Plant Metabolism, Residue Analytical Method,
             Storage Stability, and Magnitude of the Residue Data)
             Ecotoxicity (Avian Reproduction  and Seedling Emergence/Vegetative Vigor
             Studies)
             Environmental Fate (Hydrolysis, Photolysis in Water, Anaerobic and Aerobic
             Soil Metabolism, Adsorption/Desorption and Field Dissipation Data)

6.      CONTACT PERSON AT EPA

       Joanne I. Miller, Product Manager 23
       Herbicide Branch
       Registration Division (7505C)
       Office of Pesticide Programs
       Environmental Protection Agency
       Ariel Rios Building
       1200 Pennsylvania Avenue, N.W.
       Washington, DC  20460

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                                         -17-

       Office Location and Telephone Number

       Room 241, Crystal Mall Building #2
       1921 Jefferson Davis Highway
       Arlington, VA 22202
       (703) 305-6224

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
reregi strati on.

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