Document ID: EPA-HQ-OPP-2006-0481-0018
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2011-01-26T05:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460      

	OFFICE OF CHEMICAL SAFETY AND

POLLUTION PREVENTION

	

MEMORANDUM

Date:		11/30/10

SUBJECT:	Fluopicolide and its Metabolite, 2,6-Dichlorobenzamide (BAM). 
Amended Human Health Risk Assessment to Support New Section 3 Uses on
Brassica Leafy Greens Subgroup 5B, Potatoes, Sugar Beets, Carrots and to
Allow Rotation to Wheat.  

PC Code:  027412 (fluopicolide), 027402 (BAM), 027401 (dichlobenil)	DP
Barcode:  384431

Decision No.:  420445	Registration No.: 59639-139, 59639-140, 59639-142

Petition No.: 5F7016, 7E7172, 9F7617	Regulatory Action: Section 3
Registration

Risk Assessment Type:  Single Chemical Aggregate	Case No.: NA

TXR No.:  NA	CAS No.: 239110-15-7

MRID No.: NA	40 CFR: 180.627

FROM:	Donna S. Davis, Risk Assessor

		Alexandra LaMay, Biologist

Risk Assessment Branch VII

Health Effects Division (7509P)

THROUGH:	Michael S. Metzger, Chief

Risk Assessment Branch VII

Health Effects Division (7509P)

TO:		Janet Whitehurst/Tony Kish, RM-22

Fungicide Branch

Registration Division (7505P)

Attached please find an amended human health risk assessment for
fluopicolide.   This memorandum supersedes the memorandum dated 9/9/10
(D376175, D370857, D. Davis) entitled Fluopicolide and its Metabolite,
2,6-Dichlorobenzamide (BAM).  Human Health Risk Assessment to Support
New Section 3 Uses on Brassica Leafy Greens Subgroup 5B, Potatoes, Sugar
Beets, Carrots and to Allow Rotation to Wheat.  This amendment is being
issued to correct the tolerance summary table in Appendix B.  No other
changes to the previous risk assessment have been made.  Table of
Contents

  TOC \o "1-3" \h \z \u    HYPERLINK \l "_Toc271096166"  1.0	Executive
Summary	  PAGEREF _Toc271096166 \h  4  

  HYPERLINK \l "_Toc271096167"  Regulatory Recommendations	  PAGEREF
_Toc271096167 \h  7  

  HYPERLINK \l "_Toc271096168"  2.0	Ingredient Profile	  PAGEREF
_Toc271096168 \h  9  

  HYPERLINK \l "_Toc271096169"  2.1	Summary of Registered/Proposed Uses	
 PAGEREF _Toc271096169 \h  9  

  HYPERLINK \l "_Toc271096170"  2.2	Structure and Nomenclature	  PAGEREF
_Toc271096170 \h  12  

  HYPERLINK \l "_Toc271096171"  2.3	Physical and Chemical Properties	 
PAGEREF _Toc271096171 \h  13  

  HYPERLINK \l "_Toc271096172"  3.0	Hazard Characterization/Assessment	 
PAGEREF _Toc271096172 \h  14  

  HYPERLINK \l "_Toc271096173"  3.1	Hazard and Dose-Response
Characterization	  PAGEREF _Toc271096173 \h  14  

  HYPERLINK \l "_Toc271096174"  3.2	Hazard Identification and Toxicity
Endpoint Selection	  PAGEREF _Toc271096174 \h  15  

  HYPERLINK \l "_Toc271096175"  3.3	Endocrine Disruption	  PAGEREF
_Toc271096175 \h  17  

  HYPERLINK \l "_Toc271096176"  4.0	Dietary Exposure/Risk
Characterization	  PAGEREF _Toc271096176 \h  18  

  HYPERLINK \l "_Toc271096177"  4.1	Pesticide Metabolism and
Environmental Degradation	  PAGEREF _Toc271096177 \h  18  

  HYPERLINK \l "_Toc271096178"  4.1.1	Metabolism in Primary Crops	 
PAGEREF _Toc271096178 \h  18  

  HYPERLINK \l "_Toc271096179"  4.1.2	Metabolism in Rotational Crops	 
PAGEREF _Toc271096179 \h  18  

  HYPERLINK \l "_Toc271096180"  4.1.3	Metabolism in Livestock	  PAGEREF
_Toc271096180 \h  19  

  HYPERLINK \l "_Toc271096181"  4.1.4	Environmental Degradation	 
PAGEREF _Toc271096181 \h  19  

  HYPERLINK \l "_Toc271096182"  4.1.5	Pesticide Metabolites and
Degradates of Concern	  PAGEREF _Toc271096182 \h  19  

  HYPERLINK \l "_Toc271096183"  4.1.6	Analytical Methodology	  PAGEREF
_Toc271096183 \h  20  

  HYPERLINK \l "_Toc271096184"  4.1.7	Drinking Water Residue Profile	 
PAGEREF _Toc271096184 \h  20  

  HYPERLINK \l "_Toc271096185"  4.1.8	Food Residue Profile	  PAGEREF
_Toc271096185 \h  21  

  HYPERLINK \l "_Toc271096186"  4.1.9	International Residue Limits	 
PAGEREF _Toc271096186 \h  21  

  HYPERLINK \l "_Toc271096187"  4.2	Dietary Exposure and Risk	  PAGEREF
_Toc271096187 \h  22  

  HYPERLINK \l "_Toc271096188"  4.3	Anticipated Residue and Percent Crop
Treated (%CT) Information	  PAGEREF _Toc271096188 \h  23  

  HYPERLINK \l "_Toc271096189"  5.0	Residential (Non-Occupational)
Exposure/Risk Characterization	  PAGEREF _Toc271096189 \h  23  

  HYPERLINK \l "_Toc271096190"  5.1	Residential Handler Exposure and
Risk	  PAGEREF _Toc271096190 \h  23  

  HYPERLINK \l "_Toc271096191"  5.2	Residential Postapplication Exposure
and Risk	  PAGEREF _Toc271096191 \h  24  

  HYPERLINK \l "_Toc271096192"  5.3	Recreational Postapplication
Exposure	  PAGEREF _Toc271096192 \h  25  

  HYPERLINK \l "_Toc271096193"  5.4	Off Target Non-Occupational Exposure
  PAGEREF _Toc271096193 \h  25  

  HYPERLINK \l "_Toc271096194"  6.0	Aggregate Risk Assessments and Risk
Characterization	  PAGEREF _Toc271096194 \h  26  

  HYPERLINK \l "_Toc271096195"  6.1	Acute Aggregate Risk	  PAGEREF
_Toc271096195 \h  26  

  HYPERLINK \l "_Toc271096196"  6.2	Short- and Intermediate-Term
Aggregate Risk.	  PAGEREF _Toc271096196 \h  26  

  HYPERLINK \l "_Toc271096197"  6.3	Long-Term Aggregate Risk	  PAGEREF
_Toc271096197 \h  28  

  HYPERLINK \l "_Toc271096198"  6.4	Cancer Risk	  PAGEREF _Toc271096198
\h  28  

  HYPERLINK \l "_Toc271096199"  7.0	Cumulative Risk
Characterization/Assessment	  PAGEREF _Toc271096199 \h  28  

  HYPERLINK \l "_Toc271096200"  8.0	Occupational Exposure/Risk Pathway	
 PAGEREF _Toc271096200 \h  29  

  HYPERLINK \l "_Toc271096201"  8.1	Handler Exposure and Risk	  PAGEREF
_Toc271096201 \h  29  

  HYPERLINK \l "_Toc271096202"  8.2	Postapplication Exposure and Risk	 
PAGEREF _Toc271096202 \h  31  

  HYPERLINK \l "_Toc271096203"  9.0	Environmental Justice	  PAGEREF
_Toc271096203 \h  33  

  HYPERLINK \l "_Toc271096204"  10.0	Data Needs and Label
Recommendations	  PAGEREF _Toc271096204 \h  33  

  HYPERLINK \l "_Toc271096205"  10.1	Toxicology	  PAGEREF _Toc271096205
\h  33  

  HYPERLINK \l "_Toc271096206"  10.2	Residue Chemistry	  PAGEREF
_Toc271096206 \h  33  

  HYPERLINK \l "_Toc271096207"  10.3	Occupational and Residential
Exposure	  PAGEREF _Toc271096207 \h  34  

  HYPERLINK \l "_Toc271096208"  11.0	Human Studies Review	  PAGEREF
_Toc271096208 \h  34  

  HYPERLINK \l "_Toc271096209"  Appendix A:  Toxicity Profile	  PAGEREF
_Toc271096209 \h  36  

  HYPERLINK \l "_Toc271096210"  Appendix B.  Tolerance Summary	  PAGEREF
_Toc271096210 \h  44  

 1.0	Executive Summary

The Health Effects Division (HED) of EPA's Office of Pesticide Programs
has evaluated the toxicity and exposure databases for the active
ingredient, fluopicolide, and has conducted a human health risk
assessment.  The assessment was conducted to support new uses on
potatoes, sugar beets, carrots and Brassica leafy greens as well as to
allow rotation to wheat following application to primary crops. 
Fluopicolide is a fungicide which shares a metabolite,
2,6-dichlorobenzamide (BAM), with another active ingredient,
dichlobenil.  Residues of BAM are considered to be of regulatory
concern; however, separate toxicity data and endpoints for risk
assessment have been selected for BAM; therefore a separate risk
assessment is required for BAM.  However, since the new uses do not add
significantly to the BAM dietary exposure, the conclusions from the most
recently conducted BAM human health risk assessment remain unchanged and
a revised BAM risk assessment is not required to support these new uses.
 This assessment addresses risks from the parent compound and its
regulated metabolites, other than BAM.  

The principal registrant for fluopicolide is Valent U.S. A. Corporation.
 Fluopicolide is a fungicide that controls a wide range of diseases
including downy mildews, late blight, and some Pythium species.  The
requested new Section 3 uses are for the use of fluopicolide on
potatoes, sugar beets, carrots, Brassica leafy vegetables and to allow
rotation to wheat with a 30 day plant back interval (PBI).   The
petitioner is proposing the following changes to 180.627 (Tolerances
shown with a strikethrough are currently established tolerances that
would be deleted):

180.627(a) General. (1)

	Vegetable, tuberous and corm (except potato) subgroup 1D………0.02
ppm

	Vegetable, tuberous and corm subgroup
1C………………….……0.02 ppm

	Potato, processed potato
waste…………………………………..…0.05 ppm

	Vegetable root, subgroup 1A, except sugar beet and
carrot……..…0.15 ppm

	Vegetable root, subgroup
1A…………………………...………..…0.15 ppm

Brassica, leafy greens, subgroup 5B
.................................................  20 ppm

180.627 (d) Indirect or inadvertent residues.  

	Wheat, forage………………………………..0.20 ppm

	Wheat, grain…………………………………0.02 ppm

	Wheat, hay…………………………………...0.50 ppm

	Wheat, milled byproducts………………...….0.07 ppm

	Wheat, straw…………………………………0.50 ppm

	Wheat, aspirated grain fractions……………..0.07 ppm

Additionally, Valent USA has submitted PP#9F7568 proposing tolerances
for residues of the fluopicolide metabolite 2,6-dichlorobenzamide in
animal commodities to support uses on animal feed items as specified
below:

180.627 (a) General. (2)

	Cattle, Goat, Horse and Sheep, meat………….………0.02 ppm

	Cattle, Goat, Horse and Sheep, fat………….…………0.05 ppm

	Cattle, Goat, Horse and Sheep, meat byproducts……...0.05 ppm

	Milk………………………………………………...….0.01
ppm

The toxicity database for fluopicolide is complete except for
immunotoxicity testing.  No evidence of immunotoxicity was found in the
fluopicolide toxicity database.  Due to the lack of evidence of
immunotoxicity for fluopicolide, EPA does not believe that conducting
immunotoxicity testing will result in a NOAEL less than that to derive
the current cRfD.  Consequently, the Agency believes the existing data
are sufficient for endpoint selection for exposure/risk assessment
scenarios and for evaluation of the requirements under the FQPA, and an
additional database uncertainty factor does not need to be applied.  An
immunotoxicity study is considered confirmatory and should be required
as a condition of the registration of the requested new uses.  

The toxicological database indicates that technical grade fluopicolide
has relatively low acute toxicity.  Fluopicolide is not a dermal
sensitizer, primary eye irritant, or primary skin irritant.  The
subchronic and chronic toxicity studies showed that the primary effects
of fluopicolide are in the liver.  Kidney and thyroid toxicity were
observed in rats only.  Fluopicolide is not neurotoxic, carcinogenic,
nor mutagenic.  Developmental toxicity in the rabbit occurred only at
doses that caused severe maternal toxicity (including death).  In the
rat, developmental effects were seen only at high dose levels (700
mg/kg/day) in the presence of maternal toxicity.  Similarly, offspring
effects (body weight, kidney) occurred only at levels causing toxicity
in parents of the multi-generation reproductive toxicity study.  There
is no evidence of increased quantitative susceptibility of rat or rabbit
fetuses to in utero or post-natal exposure to fluopicolide.  No toxic
effects were observed in studies in which fluopicolide was administered
by the dermal routes of exposure.  The toxicological profile for
fluopicolide suggests that increased durations of exposure do not
significantly increase the severity of observed effects.  The rabbit
developmental and rat chronic/cancer studies were therefore considered
for all exposure scenarios.  The Agency considers it appropriate to
reduce the Food Quality Protection Act (FQPA) safety factor to 1X
because the toxicity database is sufficient for endpoint selection,
there is no evidence of quantitative susceptibility following in utero
and/or postnatal exposure in the rabbit and rat developmental toxicity
studies or in the 2-generation rat reproduction study, there is low
concern for the qualitative susceptibility observed in the rat
developmental toxicity study because the offspring effects (reduced
growth and skeletal defects) and late-term abortions are well
characterized and accompanied by maternal toxicity near the limit dose,
and the exposure assessments are unlikely to underestimate risk.

The Agency has reviewed the residue chemistry database, as well as the
submitted feeding studies with both parent compound and the BAM
metabolite, and concludes that tolerances are not needed in livestock
commodities at this time.  The field trial data for the Brassica leafy
greens in crop subgroup 5B was analyzed using the NAFTA maximum residue
limit (MRL) calculator.  The results of the calculator indicated that
the tolerance for this crop subgroup should be reduced to 18 ppm.  The
registrant is also requested to submit a revised Section F which
specifies this level and includes the commodity definition “Brassica,
leafy greens, subgroup 5B”.  No other changes to the proposed
tolerances are required.  

A Codex tolerance for fluopicolide has been established at 0.2 ppm for
the straw and fodder (dry) of cereal grains.  The Codex and U.S.
tolerance expressions are harmonized since they both include the parent
compound, fluopicolide, only.  However, the Codex Maximum Residue Limit
(MRL) is 0.2 ppm, a level which is lower than residue values seen in
wheat straw in U.S. field trials.  Since the Codex MRL would not cover
residues of fluopicolide in wheat straw resulting from the allowed use
pattern in the U.S., the Agency has used the NAFTA MRL calculator to
determine an appropriate tolerance level.  There are no other Codex,
Canadian, or Mexican MRLs which have been established for the other uses
which are the subject of this action. 

An acute dietary exposure and risk assessment was not conducted for
fluopicolide because an endpoint attributable to a single dose was not
identified from the available data.  Further, a cancer dietary exposure
and risk assessment was not conducted because fluopicolide is not likely
to be carcinogenic to humans.  A conservative chronic dietary exposure
and risk assessment was conducted using tolerance level residues, 100%
crop treated assumptions for most commodities, default processing
factors in the absence of empirical data and modeled drinking water
values.  Chronic dietary (food and water) estimated risks were well
below HED’s level of concern for the U.S. population and all
population subgroups.  

There are no new residential uses associated with this action; however,
fluopicolide is registered on residential turf and recreational sites,
such as golf courses.   Exposure to fluopicolide from these uses was
previously assessed.  All short- and intermediate- term handler,
postapplication and aggregate residential risks had margins of exposure
(MOEs) which were well above the level of concern of 100, and are not of
concern.  

In accordance with the FQPA, an aggregate assessment was conducted which
considered pesticide exposure and risk from the residential, food, and
water pathways.  These exposures included adults applying fluopicolide
in a residential setting (dermal and inhalation exposure),
postapplication exposure to adults and children (dermal exposure), and
postapplication oral exposure to children (by putting hands or objects
in their mouth).   The estimated aggregate short-term risks for all of
the exposure scenarios that were calculated were all below HED’s level
of concern and therefore, were not of concern.  

Occupational exposure and risk assessments were conducted for the new
uses of fluopicolide.  For handlers with baseline clothing or when
chemical-resistant gloves are worn (which is required on the proposed
label) MOEs exceeded HED’s level of concern and therefore, were not of
concern.  All occupational postapplication scenarios were also not of
concern (MOEs > LoC) with baseline personal protection.  The proposed
fluopicolide labels indicate a re-entry interval (REI) of 12 hrs, which
is in compliance with the Worker Protection Standard (WPS).

Potential areas of environmental justice concerns, to the extent
possible, were considered in this human health risk assessment, in
accordance with U.S. Executive Order 12898, "Federal Actions to Address
Environmental Justice in Minority Populations and Low-Income
Populations,"   HYPERLINK
"http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf" 
http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf ).

This assessment relies in part on data from studies in which adult human
subjects were intentionally exposed to a pesticide.  These studies have
received the appropriate ethical review.

Regulatory Recommendations

  SEQ CHAPTER \h \r 1 Provided the fluopicolide labels are amended and a
revised Section F is submitted as noted in the deficiencies section of
this memorandum, and further provided the registrations are conditioned
on the submission of the storage stability, processed commodity and
immunotoxicity data outlined below, there are no human health risk
considerations that would preclude the registrations requested on
potatoes, sugar beets, carrots, Brassica leafy green vegetables in crop
subgroup 5B and revision of the V10161 4SC label to allow rotation to
wheat with a 30 day PBI.

HED recommends that the tolerance expression for fluopicolide be revised
under 180.627(a)(1) and established under 180.627(d) to read as follows.

Tolerances are established for residues of the fungicide fluopicolide
[2,6-dichloro-N-[[3-chloro-5-(trifluoromethyl)-2-pyridinyl]methyl]benzam
ide], including its metabolites and degradates, in or on the commodities
in the table below.  Compliance with the tolerance levels specified
below is to be determined by measuring only fluopicolide
[2,6-dichloro-N-[[3-chloro-5-(trifluoromethyl)-2-pyridinyl]methyl]benzam
ide] in or on the commodity.

The submitted data supports the establishment of tolerances for residues
of fluopicolide as follows:

Tolerances to be established under 180.627 (a) General. (1)

	Vegetable, tuberous and corm subgroup 1C…...........0.02 ppm			

Potato, processed potato waste………………………0.05 ppm

Vegetable root, subgroup 1A……………………..…0.15 ppm

Brassica, leafy greens, subgroup 5B ............................ 18 ppm

Tolerances to be established under 180.627 (d) Indirect or inadvertent
residues.  

	Wheat, forage………………………………..0.20 ppm

	Wheat, grain…………………………………0.02 ppm

	Wheat, hay…………………………………...0.50 ppm

	Wheat, milled byproducts………………...….0.07 ppm

	Wheat, straw…………………………………0.50 ppm

	Wheat, aspirated grain fractions……………..0.07 ppm

Note to RD:  When the new tolerances are established, the current
tolerance on crop subgroup 1D should be deleted as it will no longer be
required.  Additionally, the current tolerance for the root vegetable
subgroup 1A, except sugar beet and carrot should be deleted.

Deficiencies 

Proposed Tolerance (Section F)

The petitioner should submit a revised Section F proposing a tolerance
of 18 ppm for residues of fluopicolide per se in “Brassica, leafy
greens, subgroup 5B”.

  SEQ CHAPTER \h \r 1 

Directions for Use

The V10161 4SC label must be amended to limit rotation only to those
crops for which there is a direct use on the label and to wheat with a
30-day plant back interval.  Additionally, “Do not use on varieties of
turnips such as fodder turnips intended for livestock use” should be
added to the V10161 4SC label.  Lastly, the label should be revised to
specify a retreatment interval of 10 days for Brassica leafy greens.

The V-10162 Premix label must be amended to limit rotation only to those
crops for which there is a direct use on the label. Additionally, the
application rates in the “Crop Specific Requirements Table” should
be listed only in terms of fluid ounces per acre or the label should be
amended to show the lbs/A for both fluopicolide and propamocarb.

860.1380 Storage Stability

Data are required on a representative root and tuber vegetable (tops and
roots) reflecting storage of fluopicolide and BAM for up to 47 months. 
While the Agency believes that given the demonstrated stability of
fluopicolide in/on a wide variety of crops for up to 30 months, residues
are not likely to substantially decline in root and tuber vegetables
stored longer than 30 months and up to 47 months, additional storage
stability data to confirm this is required as a condition of
registration.  

860.1520 Processed Food and Feed

Since residues concentrate in wheat milled byproducts, residue data and
a tolerance are required for aspirated grain fractions.  The Agency
recommends setting the aspirated grain fraction tolerance at 0.07 ppm
based on the wheat processing data; however, confirmatory residue data
on AGF is required.  

Toxicity Data

The toxicity database for fluopicolide is complete except for
immunotoxicity testing.  Recent changes to 40 CFR §158 make this study
required for pesticide registration.  No evidence of immunotoxicity was
found in the toxicity database; therefore, the Agency believes the
existing data are sufficient for endpoint selection for exposure/risk
assessment scenarios and for evaluation of the requirements under the
FQPA, and an additional database uncertainty factor does not need to be
applied.  An immunotoxicity study is considered confirmatory and should
be required as a condition of the registration of the requested new
uses.  

Ingredient Profile

Fluopicolide is a fungicide intended for the control of plant diseases
caused by Oomycetes.  Fluopicolide controls a wide range of Oomycete
(Phycomycete) diseases including downy mildews (Plasmopara,
Pseudoperonospara, Peronospora, and Bremia), late blight (Phytophthora),
and some Pythium species.  Fluopicolide appears to interfere with
mitosis and cell division resulting in the rapid destabilization of
fungal cell structures; this pesticidal mode of action has been
characterized as novel and unique and unlike the known modes of action
of other registered fungicides.  In the plant, fluopicolide is a
mesosystemic fungicide; it translocates toward the stem tips via the
xylem but it does not translocate toward the roots.

Fluopicolide is a fungicide which shares a metabolite,
2,6-dichlorobenzamide (BAM), with another active ingredient,
dichlobenil.  Residues of BAM are considered to be of regulatory
concern; however, separate toxicity data and endpoints for risk
assessment have been selected for BAM; therefore a separate risk
assessment is required for BAM.  The most recent BAM human health risk
assessment was conducted in conjunction with proposed new uses of
dichlobenil on rhubarb, caneberries, and bushberries (D354111, D. Rate,
6/19/08).  A BAM dietary exposure and risk assessment was conducted to
support that action (D373401, D. Rate, 3/19/08).  In conjunction with
the request to add uses of Brassica leafy greens, potatoes, sugar beets,
and carrots, and to allow rotation to wheat, the Agency conducted a
revised dietary exposure and risk (D381051, D. Davis, 9/910).  That
analysis demonstrated that the addition of the new uses that are the
subject of this action do not have a significant impact on the BAM
dietary exposure and risk assessment.  Since the new uses do not add
significantly to the BAM dietary exposure, the conclusions from the most
recently conducted BAM human health risk assessment cited above remain
unchanged and a revised BAM risk assessment is not required to support
these new uses.

This assessment addresses risks from the parent compound and its
regulated metabolites, other than BAM.  

 

2.1	Summary of Registered/Proposed Uses

Valent USA has submitted revised proposed labels for two end use
products.  V-10161 4 SC (EPA Reg No. 59639-140) is a suspendable
concentrate fungicide which contains 4 lbs ai/gal.  The registrant is
proposing to add uses on potatoes, sugar beets and carrots to this label
as well as to allow rotation to wheat with a 30 day PBI.  V-10162 Premix
(59639-142) is an aqueous flowable fungicide which contains 0.51 lbs
fluopicolide/gal.  The registrant proposes to only add the potato use to
this label. Additionally, Valent USA has submitted a request to amend
the V-10161 4 SC label to permit application of the active ingredient,
fluopicolide, to commodities in the Brassica leafy vegetables leafy
Brassica Subgroup 5B and has submitted a draft label for V-10161 4 SC.  

The Agency notes that V-10162 Premix is a mixed product which contains
both fluopicolide and propamocarb hydrochloride.  The 40 CFR includes a
tolerance for residues of propamocarb hydrochloride in/on potato at 0.06
ppm under 40 CFR 180.499.  The proposed use of V-10162 Premix allows for
application of propamocarb at a rate no greater than the currently
registered use of propamocarb (D266084, J. Rowell, 5/15/2000); therefore
this is not considered a new use and is covered by established
tolerances.  Additional discussion of the use of propamocarb on potatoes
is not required to support the amended registration of V-10162 Premix to
add potatoes to the label.  

The proposed use directions for all new uses of fluopicolide are
summarized in Table 2.1, below.

Table 2.1.	Summary of Directions for Use of Fluopicolide.

Trade Name	Application Timing	Application Rate

(lb ai/A)	Max. No. Applic. per Season	RTI1

(days)	Max. Seasonal Applic. Rate

(lb ai/A)	PHI

(days)	Use Directions and other Limitations

Potato

V-10161 4 SC	Postemergence	0.125	3	7 -10	0.375	7	No more than 2
sequential applications may be made.  A minimum of 20 gal/A using ground
equipment or 5 gal/A using aerial equipment.  May rotate immediately to
brassica, bulb vegetables, cucurbit vegetables, fruiting vegetables,
grapes, leafy vegetables and root and tuber vegetables.   Rotational
interval for all other crops is 18 months.  

V-10162 Premix	Postemergence	0.09-0.11	4	10	0.35	7	No more than 2
sequential applications may be made.  A minimum of 20 gal/A using ground
equipment or 5 gal/A using aerial equipment.  May rotate immediately to
cucurbit vegetables, fruiting vegetables, leafy vegetables and potatoes.
 Rotational interval for all other crops is 18 months.  

Sugar Beet

V-10161 4 SC	Postemergence	0.09 - 0.125	4	7 -14	0.375	7	No more than 2
sequential applications may be made.  A minimum of 20 gal/A using ground
equipment or 5 gal/A using aerial equipment.  May rotate immediately to
brassica, bulb vegetables, cucurbit vegetables, fruiting vegetables,
grapes, leafy vegetables and root and tuber vegetables.   Rotational
interval for all other crops is 18 months.  

Carrots

V-10161 4 SC	Postemergence	0.125	3	7 -14	0.375	7	No more than 2
sequential applications may be made.  A minimum of 20 gal/A using ground
equipment or 5 gal/A using aerial equipment.  May rotate immediately to
brassica, bulb vegetables, cucurbit vegetables, fruiting vegetables,
grapes, leafy vegetables and root and tuber vegetables.   Rotational
interval for all other crops is 18 months.  

Leafy Brassica Greens Subgroup 5B:  Broccoli raab, Chinese cabbage (bok
choy), Collards, Kale, Mizuna, Mustard greens, Mustard spinach, Rape
greens.

V-10161 4 SC	Postemergence	0.09-0.125	4	7-10	0.375	2	Ground or aerial
foliar application.   Apply a minimum of 20 gal/A ground or 5 gal/A
aerial.  Apply no more than 2 sequential applications before alternating
with another fungicide.  Do not apply to greenhouse food crops.  All
crops other than those for which there is a direct use may not be
rotated before 18 months.

RTI = Retreatment interval

The Agency has identified several issues with the labels submitted with
the uses on potatoes, sugar beets, carrots and the Brassica leafy
greens.  The following revisions to the label are required prior to
registration on the new uses:

The V10161 4SC label must be amended to limit rotation only to those
crops for which there is a direct use on the label and to wheat with a
30-day PBI.   Additionally, “Do not use on varieties of turnips such
as fodder turnips intended for livestock use” should be added to the
V10161 4SC label.  Lastly, the label should be revised to specify a RTI
of 10 days for Brassica leafy greens.

The V-10162 Premix label must be amended to limit rotation only to those
crops for which there is a direct use on the label. Additionally, the
application rates in the “Crop Specific Requirements Table” should
be listed only in terms of fluid ounces per acre or the label should be
amended to show the lbs/A for both fluopicolide and propamocarb.

Structure and Nomenclature

The structure and nomenclature for the parent compound, fluopicolide is
shown in Table 2.2.1.  The names and structures of its regulated
metabolites are shown in Table 2.2.2.

Table 2.2.1.		Fluopicolide Nomenclature.

Chemical structure	

Empirical Formula	C14H8Cl3F3N2O

Common name	Fluopicolide

Company experimental name	AE C638206 

IUPAC name
2,6-dichloro-N-[3-chloro-5-(trifluoromethyl)-2-pyridylmethyl]benzamide 

CAS name
2,6-dichloro-N-[[3-chloro-5-(trifluoromethyl)-2-pyridinyl]methyl]benzami
de 

CAS Registry Number	239110-15-7 

End-use products (EPs)	V-10161 4SC Fungicide (39.5% fluopicolide; EPA
File Symbol No. 59639-RUN)

V-10161 Premix Fungicide (5.54% fluopicolide and 55.4% propamocarb; EPA
File Symbol No. 59639–RUE)

Chemical Class	Fungicide

Known Impurities of Concern	None

Table 2.2.2.  Chemical Names and Structures of Regulated Fluopicolide
Metabolites.

Common name/code	Chemical name	Chemical structure

BAM

AE C653711

	2,6-dichlorobenzamide	

PCA

AE C657188

	3-chloro-5-trifluoromethylpyridine-2-carboxylic acid 	

P1X

AE 1344122

	3-methylsulfinyl-5-trifluoromethylpyridine-2-carboxylic acid	

2.3	Physical and Chemical Properties  TC \l2 "2.3	Physical and Chemical
Properties 

The physical and chemical properties for fluopicolide are shown in Table
2.3, below.

Table 2.3.		Physicochemical Properties of Fluopicolide.

Parameter	Value	Reference

Molecular Weight	383.59	*

Melting point/range 	149 (C 	MRID 46474015

pH 	6.5 at 22.0 (C (1% suspension) 	MRID 46474013

Density 	1.65 g/cm3 (30 °C)	MRID 46474016

Water solubility (20 (C) 	2.86 mg/L at pH 4

2.80 mg/L at pH 7

2.80 mg/L at pH 9 	MRID 46474021

Solvent solubility (g/L at 20 (C) 	n-Hexane:	0.20

Ethanol:	19.2

Toluene:	20.5

Ethyl acetate:	37.7

Acetone:	74.7

Dichloromethane:	126

Dimethyl sulfoxide:	183 	MRID 46474022

Vapor pressure (25 (C) 	8.03 x 10-7 Pa 	MRID 46474023

Dissociation constant (pKa) 	No evidence of ionization in the pH range
of 1.9 to 9.8 	MRID 46474017

Octanol/water partition coefficient Log(KOW) 	Log POW = 3.26 at pH 7.8
and 22 ± 1 (C 	MRID 46474018

	Log POW = 2.9 at pH 4.0, 7.3 and 9.1 and 40 (C 	MRID 46474019

UV/visible absorption spectrum 	Absorption maxima wavelengths (nm): 

	In methanol:	203 and 271

	In methanol/HCl:	202 and 270

	In methanol/NaOH:	219 and 271 	MRID 46474014

*The molecular weight was calculated from the Periodic Table.

Hazard Characterization/Assessment

D325091, N. Dodd, 11/21/07

3.1	Hazard and Dose-Response Characterization

  TC \l1 "3.0	Hazard Characterization/Assessment 

The toxicity database for fluopicolide is complete except for
immunotoxicity testing.  Recent changes to 40 CFR §158 make this study
required for pesticide registration.  EPA has evaluated the available
fluopicolide toxicity database to determine whether an additional
database uncertainty factor is needed to account for potential
immunotoxicity. No evidence of immunotoxicity was found.  Due to the
lack of evidence of immunotoxicity for fluopicolide, EPA does not
believe that conducting immunotoxicity testing will result in a NOAEL
less than that to derive the current cRfD.  Consequently, the Agency
believes the existing data are sufficient for endpoint selection for
exposure/risk assessment scenarios and for evaluation of the
requirements under the FQPA, and an FQPA database uncertainty factor
does not need to be retained.  An immunotoxicity study is considered
confirmatory and should be required as a condition of the registration
of the requested new uses.  

Fluopicolide has demonstrated low to moderate acute toxicity by the oral
(Toxicity Category III), dermal (IV) and inhalation routes (IV).  It is
not an eye or dermal irritant and is not a dermal sensitizer.  Repeat
exposure studies result mainly in changes in body weight and weight gain
at oral dose levels of 109 mg/kg/day and above in rats, mice and dogs. 
No definitive cross-species target organ was identified in subchronic or
chronic studies with fluopicolide.  Adverse liver effects (hepatic oval
cell proliferation and altered liver cell foci) were observed in mice at
dose levels of 551 mg/kg/day and above. Kidney toxicity was observed in
the subchronic study in males rats only at 174 mg/kg/day and in both
genders at 144 mg/kg/day in the reproduction study.  Thyroid toxicity
was observed in the chronic rat study in male rats at 109 mg/kg/day.  A
dermal subchronic toxicity study showed no systemic or local effects at
the limit dose. 

Fluopicolide is not likely to be carcinogenic to humans.  There was no
evidence of carcinogenicity in rats, but hepatocellular adenomas were
observed in mice at dose levels of 551 mg/kg/day and above. 
Developmental toxicity in the rabbit occurred only at doses that caused
severe maternal toxicity (including death).  In the rat, developmental
effects were seen only at high dose levels (700 mg/kg/day) in the
presence of maternal toxicity.  Similarly, offspring effects (body
weight, kidney) occurred only at levels causing toxicity in parents of
the multi-generation reproductive toxicity study.  No evidence of
neurotoxicity was seen in acute or subchronic oral rat neurotoxicity
studies.

Available in vivo dermal absorption data on fluopicolide indicated a
dermal absorption factor of 37% in rats.  In vitro dermal absorption
data suggested that fluopicolide will penetrate human skin at a
substantially lower rate (up to eight times less) than rat skin,
providing confidence that a 37% dermal absorption factor is conservative
for use in this risk assessment.

HED recommends that the FQPA Safety Factor be reduced to 1X because
there is a complete toxicity database for fluopicolide and there is no
evidence of quantitative susceptibility following in utero and/or
postnatal exposure in the rabbit and rat developmental toxicity studies
or in the 2-generation rat reproduction study.  There is low concern for
qualitative susceptibility observed in the rat developmental toxicity
study because the fetal effects (reduced growth and skeletal defects)
and late-term abortions are well characterized and accompanied by
maternal toxicity near the limit dose.  Protection of the maternal
effects also protects for any effects that may occur during development.
 There are no residual uncertainties concerning pre- and post-natal
toxicity and there are no neurotoxicity concerns.  A conservative
endpoint from the rabbit developmental study was used for all exposure
scenarios.  Furthermore, the dietary exposure assessment is not likely
to under estimate risk.  Finally, HED used similarly conservative
assumptions to assess post-application exposure of children as well as
incidental oral exposure of toddlers.

		

3.2	Hazard Identification and Toxicity Endpoint Selection  TC \l2 "3.5
Hazard Identification and Toxicity Endpoint Selection 

The toxicity endpoints and doses for risk assessment were selected based
upon the available toxicity data and the use exposure information on
fluopicolide. The rabbit developmental and rat chronic/carcinogenicity
studies were considered co-critical for endpoint selection.  The
toxicological profile for fluopicolide suggests that increased durations
of exposure does not significantly increase the severity of observed
effects.  The rabbit developmental and rat chronic/cancer studies were
therefore considered for all exposure scenarios.  For the rabbit
developmental study, the maternal LOAEL was 60 mg/kg/day based on death,
abortions/premature deliveries (late-term), decreased food consumption,
and decreased body weight gain.  The maternal NOAEL was 20 mg/kg/day. 
In the combined chronic toxicity/carcinogenicity study in rats the LOAEL
was 109 mg/kg/day based on decreased body weight gain and increased
thyroid weight and increased incidence of thyroid lesions with a NOAEL
of 31.5 mg/kg/day.  The NOAEL/LOAEL from the rabbit developmental study
was used for the point of departure since it is protective of effects
observed from similar dosing of the chronic/carcinogenicity rat study. 
The selected endpoints and doses are presented below.



Table 3.2.   Summary of Toxicological Doses and Endpoints for
Fluopicolide for Use in Dietary and Occupational Human Health Risk
Assessments

Exposure/

Scenario	Point of Departure	Uncertainty/

FQPA Safety Factors	RfD, PAD, Level of Concern for Risk Assessment	Study
and Toxicological Effects

Acute Dietary 

(all populations)	An endpoint attributable to a single dose was not
identified from the available data.

Chronic Dietary (all populations)	Maternal

NOAEL=20 mg/kg/day	UFA=10x

UFH=10x

FQPA SF = 1X	Chronic RfD = 

0.2 mg/kg/day

cPAD = 0.2 mg/kg/day	Developmental Toxicity Study in Rabbits

LOAEL (maternal) = 60 mg/kg/day based on death, abortions/ premature
deliveries, decreased food consumption and body weight gain.

Co-critical: Chronic/Oncogenicity Study in Rats

NOAEL = 31.5 mg/kg/day. 

LOAEL = 109.4 mg/kg/day based on decreased body weight gain and
increased thyroid weight and increased incidence of thyroid lesions.

Incidental Oral Intermediate-Term

(1 - 6 months)	Maternal  NOAEL = 20 mg/kg/day	UFA=10x

UFH=10x

FQPA SF = 1X	MOE = 100 (occupational)

MOE = 100 (residential)	Developmental Toxicity Study in Rabbits

LOAEL (maternal) = 60 mg/kg/day based on death, abortions/ premature
deliveries, decreased food consumption and body weight gain.

Dermal Short-  Intermediate- and Long-Term (1-30 days, 1-6 months, and
>6 months)	Maternal  NOAEL = 20 mg/kg/day	UFA=10x

UFH=10x

FQPA SF = 1X

37% dermal absorption	MOE = 100 (occupational)

MOE = 100 (residential)	Developmental Toxicity Study in Rabbits

LOAEL (maternal) = 60 mg/kg/day based on death, abortions/ premature
deliveries, decreased food consumption and body weight gain.

Co-critical: Chronic/Oncogenicity Study in Rats

NOAEL = 31.5 mg/kg/day.

LOAEL = 109.4 mg/kg/day based on decreased body weight gain and
increased thyroid weight and increased incidence of thyroid lesions.

Inhalation Short- Intermediate- and Long-term (1-30 days,  1-6 months,
and >6 months)	Maternal  NOAEL = 20 mg/kg/day	UFA=10x

UFH=10x

FQPA SF = 1X

(inhalation and oral toxicity are assumed to be equivalent)	MOE = 100
(occupational)

MOE = 100 (residential)	Developmental Toxicity Study in Rabbits

LOAEL (maternal) = 60 mg/kg/day based on death, abortions/ premature
deliveries, decreased food consumption and body weight gain.

Co-critical: Chronic/Oncogenicity Study in Rats

NOAEL = 31.5 mg/kg/day.

LOAEL = 109.4 mg/kg/day based on decreased body weight gain and
increased thyroid weight and increased incidence of thyroid lesions.

Cancer (oral, dermal, inhalation)	Classification:  “Not Likely to be
Carcinogenic to Humans”.

Point of Departure (POD) = A data point or an estimated point that is
derived from observed dose-response data and  used to mark the beginning
of extrapolation to determine risk associated with lower environmentally
relevant human exposures.  NOAEL = no observed adverse effect level. 
LOAEL = lowest observed adverse effect level.  UF = uncertainty factor. 
UFA = extrapolation from animal to human (interspecies).  UFH =
potential variation in sensitivity among members of the human population
(intraspecies).  FQPA SF = FQPA Safety Factor.  PAD = population
adjusted dose (a = acute, c = chronic).  RfD = reference dose.  MOE =
margin of exposure.  LOC = level of concern.  N/A = not applicable.

3.3	Endocrine Disruption  

As required under FFDCA section 408(p), EPA has developed the Endocrine
Disruptor Screening Program (EDSP) to determine whether certain
substances (including pesticide active and other ingredients) may have
an effect in humans or wildlife similar to an effect produced by a
“naturally occurring estrogen, or other such endocrine effects as the
Administrator may designate.”  The EDSP employs a two-tiered approach
to making the statutorily required determinations. Tier 1 consists of a
battery of 11 screening assays to identify the potential of a chemical
substance to interact with the estrogen, androgen, or thyroid (E, A, or
T) hormonal systems.  Chemicals that go through Tier 1 screening and are
found to have the potential to interact with E, A, or T hormonal systems
will proceed to the next stage of the EDSP where EPA will determine
which, if any, of the Tier 2 tests are necessary based on the available
data. Tier 2 testing is designed to identify any adverse endocrine
related effects caused by the substance, and establish a dose-response
relationship between the dose and the E, A, or T effect.

Between October 2009 and February 2010, EPA issued test orders/data
call-ins for the first group of 67 chemicals, which contains 58
pesticide active ingredients and 9 inert ingredients.  This list of
chemicals was selected based on the potential for human exposure through
pathways such as food and water, residential activity, and certain
post-application agricultural scenarios.  This list should not be
construed as a list of known or likely endocrine disruptors.

Fluopicolide is not among the group of 58 pesticide active ingredients
on the initial list to be screened under the EDSP.  Under FFDCA sec.
408(p) the Agency must screen all pesticide chemicals.  Accordingly, EPA
anticipates issuing future EDSP test orders/data call-ins for all
pesticide active ingredients. 

For further information on the status of the EDSP, the policies and
procedures, the list of 67 chemicals, the test guidelines and the Tier 1
screening battery, please visit our website:    HYPERLINK
"http://www.epa.gov/endo/"  http://www.epa.gov/endo/ .

4.0	Dietary Exposure/Risk Characterization tc "5.0	Dietary Exposure/Risk
Characterization" 

4.1	Pesticide Metabolism and Environmental Degradation

D336216, F. Fort, 3/6/08, Human Health Risk Assessment

D370762, D. Davis, 8/19/10, Residue Chemistry Chapter

D370855, D. Davis, 7/26/10, Residue Chemistry Chapter

4.1.1	Metabolism in Primary Crops

Based on acceptable grape, lettuce, and potato metabolism studies, the
qualitative nature of the residue in primary plants is adequately
understood.  HED has determined that the tolerance expression for all
primary crops should include fluopicolide per se.  For risk assessment
purposes, the residue of concern for the tuberous and corm vegetables
includes the parent compound, fluopicolide, and its metabolites,
3-chloro-5-trifluoromethylpyridine-2-carboxylic acid (PCA) and BAM.  For
all other primary crops, the residue of concern for risk assessment
purposes includes the parent compound and the metabolite, BAM.

Metabolism in Rotational Crops

accumulated at ≥0.01 ppm in all rotated crop matrices planted at the
29-, 133-, or 365-day plant back intervals (PBI).  Therefore, the
available confined rotation crop data demonstrate the potential for
quantifiable residues of fluopicolide and its metabolites in rotational
crops at a 12 month PBI.  No data were provided to elucidate potential
residues in rotational crops at longer PBIs.  The tolerance expression
for rotational crops is fluopicolide (parent) only.  The residues of
concern for the risk assessment for cereal grains as rotational crops
are fluopicolide (parent), BAM, PCA, and P1X in grain for human food,
and fluopicolide (parent) and BAM in forage/hay/straw and grain for
livestock feed.  The residues of concern for the risk assessment for all
rotational crops except cereal grains are fluopicolide (parent) and BAM.
 

4.1.3	Metabolism in Livestock

Based on acceptable ruminant and poultry metabolism studies, the
qualitative nature of the residue in livestock is adequately understood.
 The residue of concern in animal commodities for tolerance setting
purposes is the parent compound, fluopicolide, only.  The residue of
concern for risk assessment purposes in animal commodities is
fluopicolide and its BAM metabolite.  

Environmental Degradation

The Agency has determined, based on two aerobic soil metabolism studies,
that the residues of concern in drinking water are parent fluopicolide
and the degradate BAM (Fluopicolide Risk Assessment Team, 4/12/07).  BAM
appears to be a major degradate and was present in levels up to 40%. 
This risk assessment will address residues of fluopicolide in water
only.  Risks from exposure to BAM in water will be addressed in the BAM
Human Health Risk Assessment being conducted concurrently with this
assessment.

4.1.5	Pesticide Metabolites and Degradates of Concern

A summary of the fluopicolide residues of concern is shown in Table
4.1.5, below.

Table 4.1.5.  Summary of Fluopicolide Residues of Concern.

Matrix	Residues included in Risk Assessment	Residues included in
Tolerance Expression

Plants

	Primary Crops

	All primary crops except Tuberous and Corm Vegetables	Fluopicolide
(parent) and BAM 	Fluopicolide

	Tuberous and Corm Vegetables	Fluopicolide (parent), PCA, and BAM

Rotational Crops

	All rotational crops except cereal grains	Fluopicolide (parent) and BAM
Fluopicolide

	Cereal grains - grain for human food 	Fluopicolide (parent), PCA, P1X
and BAM

Cereal grains - forage/hay/straw and grain for livestock feed
Fluopicolide (parent) and BAM 

	Livestock	Fluopicolide (parent) and BAM 	Fluopicolide1

Drinking Water	Fluopicolide (parent) and BAM 	Not applicable

4.1.6	Analytical Methodology

An acceptable LC/MS/MS enforcement method RM-43C-2 is available to
enforce all tolerances now proposed to support the use on potatoes,
sugar beets, carrots, rotational wheat and Brassica leafy greens. 
Briefly, homogenized plant matrices are mixed with acetone/water, and
the mixture is acidified.  An aqueous solution of L-cysteine
hydrochloride is added, and the sample is extracted.  The extract is
isolated by gravity filtration and diluted to volume with acetone and
water.  An aliquot of the extract is concentrated to remove the acetone,
and the concentrated extract is partitioned twice with methyl t-butyl
ether (MTBE).  The MTBE phases are combined, and an aliquot is
evaporated to dryness, redissolved in acetonitrile/water, and then
filtered for LC/MS/MS analysis.  For Method RM-43C-2, the primary
analytical column is packed with reversed-phase C18.  Additionally the
method provides for an alternative column packed with a mixed phase of
C18 plus a strong cation exchange packing material.  The LC/MS/MS method
has a limit of quantitation (LOQ) for fluopicolide of 0.01 ppm.  

Drinking Water Residue Profile

Fluopicolide is not included as an analyte monitored in U.S. surface and
groundwater under the USGS’s National Water Quality Assessment (NAWQA)
program.  Since there is not adequate monitoring data available, surface
water concentrations were estimated using the Tier II model PRZM version
3.12/ EXAMS version 2.98.  Ground water concentrations were estimated
using the Tier I SCI-GROW model. 

The recommended estimated drinking water concentrations (EDWCs) for
fluopicolide are summarized below.

Table 4.1.7.  Summary of Estimated Surface Water and Groundwater
Concentrations for Fluopicolide.

	Fluopicolide

	Surface Water Conc., ppb 1	Groundwater Conc., ppb 2

Acute	25.50	0.5

Chronic (non-cancer)	24.14

	Chronic (cancer)	22.36

	1 From the Tier II PRZM-EXAMS - Index Reservoir model.  Highest surface
water EDWC assumed a maximum application rate of 0.125 lbs ai/A, a
maximum number of applications of 3 and an RTI of 7 days.  For the
premix label a maximum application rate of 0.09 lbs ai/A, a maximum of 4
applications and a 10 day RTI were evaluated but did not lead to the
highest EDWC values.  The scenario that gave the maximum acute and
chronic (non cancer) EDWCs were aerial application to Florida Carrots. 
The scenario that gave the maximum cancer EDWC was aerial application to
potatoes.

 2 From the SCI-GROW model assuming 3 applications of   0.125 lbs ai/A.

Note:  Since only a chronic dietary assessment was conducted, the value
of 24.14 ppb is the value used to calculate exposure and risk.

Food Residue Profile

Meat, Milk, Poultry and Eggs

Provided the registrant amends the label to prohibit use of turnip tops
as a livestock feed item, the Agency concludes that adequate data are
available to assess the potential for the transfer of residues of
fluopicolide and its regulated metabolites to meat, milk, poultry and
eggs.  Based on the calculated maximum reasonably balanced diet for
livestock, the Agency concludes that there is not likely to be transfer
of residues of fluopicolide to ruminant commodities.  No new animal
tolerances are needed to support uses on potatoes, sugar beets, carrots
and rotational wheat.  Further, given the very low calculated dietary
burden for poultry, residues are not likely in poultry commodities as a
result of feeding feedstuffs treated with fluopicolide.

Potato (as a part of crop subgroup 1C, tuberous and corm vegetables)

The Agency concludes that the submitted potato field trial data are
adequate.  The number and geographic representation of the field trials
were in accordance with OPPTS guideline 860.1500 to support a tolerance
for the tuberous and corm crop subgroup 1C.  The data support the
establishment of a tolerance of 0.02 ppm for the crop subgroup. 
Adequate potato processing data have been submitted.  A tolerance for
processed potato waste at 0.05 ppm is required.  

Sugar Beet and Carrots (as a part of crop subgroup 1A, root vegetables)

The Agency concludes that the submitted sugar beet and carrot field
trial data are adequate.  The number and geographic representation of
the field trials when considered with previously submitted radish data
were in accordance with OPPTS guideline 860.1500 to support a tolerance
for the root vegetables subgroup 1A.  The data support a tolerance of
0.15 pm for the subgroup.  Adequate sugar beet processing data have been
submitted.  No tolerances are required for processed commodities.  

Brassica Leafy Vegetables

The submitted mustard green field trial data are acceptable.  The number
and geographic representation of the field trial data are in accordance
with OPPTA guideline 860.1500 to support a tolerance for the Brassica
leafy greens subgroup 5B.  The data support a tolerance of 18 ppm for
the subgroup.  

International Residue Limits

A Codex tolerance for fluopicolide has been established at 0.2 ppm for
the straw and fodder (dry) of cereal grains.  The Codex and U.S.
tolerance expressions are harmonized, as they both include the parent
compound, fluopicolide, only.  However, the Codex MRL is 0.2 ppm, a
level which is lower than residues values seen in wheat straw in U.S.
field trials.  Since the Codex MRL would not cover residues of
fluopicolide in wheat straw resulting from the allowed use pattern in
the U.S., the Agency has used the NAFTA MRL calculator to determine an
appropriate tolerance level.  There are no other Codex, Canadian, or
Mexican MRLs which have been established for the other uses which are
the subject of this action. 

4.2	Dietary Exposure and Risk

D381050, D. Davis, 8/19/10, Dietary Exposure and Risk Assessment

A chronic aggregate dietary (food and drinking water) exposure and risk
assessment was conducted using the Dietary Exposure Evaluation Model
DEEM-FCID™, Version 2.03 which use food consumption data from the U.S.
Department of Agriculture’s Continuing Surveys of Food Intakes by
Individuals (CSFII) from 1994-1996 and 1998.  

Acute Dietary Exposure Results and Characterization

An acute dietary exposure and risk assessment was not conducted because
an endpoint attributable to a single dose has not been identified for
fluopicolide.

Chronic Dietary (Food and Drinking Water) Exposure Results and
Characterization

Chronic dietary risks for the U.S Population and all population
subgroups are not of concern.  The established and newly proposed uses
of fluopicolide result in an estimated exposure to the U.S. Population
which is equivalent to 7.9% of the chronic population adjusted dose
(cPAD).  The most highly exposed subgroup is children 1 – 2 years of
age with an estimated exposure equivalent to 13% of the cPAD.  This
assessment is considered highly conservative as it includes tolerance
level residues or maximum field trial residue levels for all crops,
assumes 100% crop treated and uses empirical or default DEEM processing
factors.  

Cancer Dietary Exposure Results and Characterization

A cancer dietary exposure and risk assessment was not conducted since
fluopicolide is not likely to be carcinogenic to humans.  

The results of the dietary exposure and risk assessment are summarized
in Table 4.2, below.

Table 4.2.  Chronic Dietary Exposure and Risk Estimates for
Fluopicolide.

Population Subgroup	PAD

(mg/kg/day)	DEEM-FCID

Exposure

(mg/kg/day)	% PAD

U.S. Population	0.2	0.015802	7.9

All infants (< 1 yr)

0.011551	5.8

Children 1-2 yrs

0.025218	13

Children 3-5 yrs

0.022429	11

Children 6-12 yrs

0.016355	8.2

Youth 13-19 yrs

0.012912	6.5

Adults 20-49 yrs

0.015330	7.7

Adults 50+ yrs

0.015395	7.7

Females 13-49 yrs

0.015339	7.7

4.3	Anticipated Residue and Percent Crop Treated (%CT) Information

The fluopicolide dietary exposure and risk assessment did not use any
anticipated residue or percent crop treated information.

5.0	Residential (Non-Occupational) Exposure/Risk Characterization

D347228, K. O’Rourke, 12/13/07, ORE Assessment

D326082, K. O’Rourke, 10/9/07, ORE Assessment

A residential exposure and risk assessment was previously conducted
(D326082, K. O’Rourke, 10/09/07) for two products containing
fluopicolide (V-10161 and V-10162) which were proposed for application
to residential turfgrass and recreational sites.  The exposure scenarios
and risk are summarized in the following sections.  In this assessment,
two modifications were made to the exposure assessment previously
conducted to make them consistent with current practice.  First, HED
completed only short-term assessments for residential handler scenarios
as these exposures are assumed to be episodic, not daily. The previous
exposure assessment completed both short- and intermediate-term exposure
assessments for residential handlers.  Second, HED combined only dermal
and hand-to-mouth exposures for residential postapplication exposure to
children.  The previous exposure assessment combined dermal and all
incidental oral exposures.

The products may be applied to turf at rates ranging from 0.21 to 0.27
lb ai/A, for two applications at an interval of 14 days.  The labels do
not prohibit homeowners from using these products; therefore,
residential handlers may receive short-term dermal and inhalation
exposure to fluopicolide when mixing, loading and applying the
formulations.  Dermal exposure is likely for adults and children
entering treated lawns.  Toddlers may also experience exposure via
incidental non-dietary ingestion (i.e., hand-to-mouth, object-to-mouth
(turfgrass), and soil ingestion) during postapplication activities on
treated turf.

5.1	Residential Handler Exposure and Risk	

HED’s Draft Standard Operating Procedures (SOPs) for Residential
Exposure Assessments, and Recommended Revisions (HED Policy Number 11,
revised 22 Feb 2001), were used as the basis for the residential handler
exposure calculations.   Data from the Outdoor Residential Exposure Task
Force (ORETF) (MRID # 44972201) were used in this assessment in place of
PHED data for the garden hose-end sprayer scenario, which provided more
confidence in the exposure estimate.  HED completed only short-term
assessments for residential handler scenarios as these exposures are
assumed to be episodic, not daily. As shown in Table 6, the Total MOEs
for residential handlers are well above the LOC of 100, and are not of
concern.



Table 5.1.  Handler Exposure and Risk Estimates for Residential Lawn
Applicators

Handler Scenario	Application Rate 1

 (lb ai/A)	Area Treated 2

(acres/day)	Unit Exposure 3

(mg/lb ai)	Short-Term

Daily Dose 4

(mg/kg/day)	Total MOE 5

(1) Mix/load and spot application of liquid formulation (low-pressure
hand sprayer)	0.27	0.023

(1,000 ft2)	Dermal:

100	Dermal:

0.0038	5,200

	Inhalation:

0.030	Inhalation:

0.0000031

	(2) Mix/load and broadcast application of liquid formulation (garden
hose-end sprayer)	0.27	0.50	Dermal:

11	Dermal:

0.0092	2,200

	Inhalation:

0.017	Inhalation:

0.000038

	1 Application rate is based on maximum values found in proposed labels:
V-10161 VPP Fungicide (Reg No. 59639-RUR), and V-10162 VPP Fungicide
(Reg. No. 59639-RUG). 

2 Area treated is based on the area that can be reasonably treated in a
single day based on the application method (standard EPA/OPP/HED
values).

3 Dermal unit exposure values represent short pants and short-sleeved
shirt; inhalation values represent no respirator.  Values for
low-pressure handwand are reported in the PHED Surrogate Exposure Guide
dated August 1998, and those for hose-end sprayer were obtained from the
ORETF data.

4 Daily Absorbed Dose (mg/kg/day) = ([unit exposure * % absorption] *
Application rate * Area treated) / 60 kg;

where dermal absorption is 37% and inhalation absorption is assumed to
be 100%.

5 Short-Term Total MOE = NOAEL (20 mg/kg/day) / Total Daily Absorbed
Dose (dermal + inhalation).  The LOC is 100.	

5.2	Residential Postapplication Exposure and Risk

The following postapplication exposure scenarios resulting from lawn
treatment were assessed: (1) adult and toddler postapplication dermal
exposure, (2) toddler’s incidental ingestion of pesticide residues on
lawns from hand-to-mouth transfer, (3) toddlers’ object-to-mouth
transfer from mouthing of pesticide-treated turfgrass, and (4)
toddlers’ incidental ingestion of soil from pesticide-treated
residential areas.  HED completed short- and intermediate-term
post-application assessments as HED believes that these scenarios may
occur over a single day or up to weeks at a time.  

Turf transferrable residue (TTR) data were not available.  The
assessment was based on generic assumptions for TTR and transfer
coefficients, as specified by the Recommended Revisions to the
Residential SOPs and recommended approaches by HED’s Science Advisory
Council for Exposure (ExpoSAC).

The exposure and risk estimates for the residential exposure scenarios
are assessed for the day of application (day “0”) because it is
assumed that adults and toddlers could contact the lawn immediately
after application.  Since toxicity endpoints are identical for different
durations of exposure, the short-term risk assessment is protective of
intermediate-term exposure; therefore, exposures are shown to be the
same for both durations.  The short-/intermediate-term MOEs for each
scenario are above the LOC of 100, and are not of concern.  As mentioned
previously, the same toxicity endpoint and study were selected to
evaluate all routes of exposure; therefore, the MOEs were combined for
children.  As shown in Table 5.2., all individual and total MOEs are
greater than the LOC of 100 on the day of application, and therefore,
are not of concern.

Table 5.2.  Post Application Exposure and Risk Estimates from
Residential Lawns

Scenario and 

Pathway	TTR/GR/SR0 (µg/cm2 or g) 1	PDR0-norm

(mg/kg/day) 2	Short-/ Int-Term

 MOE 3	Total MOE 4

Adult’s Scenarios

(1) Dermal Postapplication	0.15	0.027	740	NA

Children’s Scenarios

(1) Dermal 	0.15	0.039	520	470

(2) Hand-to-Mouth	0.15	0.0040	5,000

	

(3) Mouthing Grass/Object	0.88	0.0015	14,000	NA

(4) Soil Ingestion	2.0	0.000014	1,500,000

	1 TTR=turf transferable residue on day “0"; GR=grass/object residue
on day “0"; SR0=soil residue on day “0".  Data for the Fraction of
ai Transferrable from the Foliage to assess Object to Mouth exposure
from MRID#: 46708641).  Soil ingestion residue presented in ug/gram;
other residue values in ug/cm2.

2 PDR0norm=potential dose rate on day “0”.

3 MOE = NOAEL/PDR; where Short-/Intermediate-term NOAEL = 20 mg/kg/day.

4 Total MOE = 1/ [(1/MOEDermal) + (1/MOEHand-to-Mouth).  Note: In the
residential assessment D326082, K. O’Rourke, 10/09/07, Dermal,
Hand-to-Mouth, Object-to-Mouth and Soil Ingestion exposures were
combined.  It is now policy to only combine Dermal and Hand-to-Mouth
exposures.

Based on the Agency's current practices, a quantitative postapplication
inhalation exposure assessment was not performed for fluopicolide at
this time.  However, volatilization of pesticides may be a potential
source of postapplication inhalation exposure to individuals nearby to
pesticide applications.  The Agency sought expert advice and input on
issues related to volatilization of pesticides from its Federal
Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel
(SAP) in December 2009.  The Agency received the SAP’s final report on
March 2, 2010
(http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html).  The
Agency is in the process of evaluating the SAP report and may, as
appropriate, developing policies and procedures, to identifying the need
for and, subsequently, the way to incorporate postapplication inhalation
exposure into the Agency's risk assessments.  If new policies or
procedures are put into place, the Agency may revisit the need for a
quantitative postapplication inhalation exposure assessment for
fluopicolide.

5.3	Recreational Postapplication Exposure

Recreational exposures to turf (including playing golf) are expected to
be similar to, or in many cases less than, those evaluated in section
5.2 Residential Postapplication Exposure and Risk; therefore, a separate
recreational exposure assessment was not included.

5.4	Off Target Non-Occupational Exposure

Spray drift is always a potential source of exposure to residents nearby
to spraying operations.  This is particularly the case with aerial
application, but, to a lesser extent, could also be a potential source
of exposure from the ground application method employed for
fluopicolide.  The Agency has been working with the Spray Drift Task
Force, EPA Regional Offices and State Lead Agencies for pesticide
regulation and other parties to develop the best spray drift management
practices.  On a chemical by chemical basis, the Agency is now requiring
interim mitigation measures for aerial applications that must be placed
on product labels/labeling.  The Agency has completed its evaluation of
the new database submitted by the Spray Drift Task Force, a membership
of U.S. pesticide registrants, and is developing a policy on how to
appropriately apply the data and the AgDRIFT computer model to its risk
assessments for pesticides applied by air, orchard airblast and ground
hydraulic methods.  After the policy is in place, the Agency may impose
further refinements in spray drift management practices to reduce
off-target drift with specific products with significant risks
associated with drift.

Note that, as indicated in this assessment, fluopicolide is directly
applied to residential turf and does not result in exposures of concern.
 It is unlikely that the potential for risk of exposure to spray drift
from the agricultural uses would be higher than that estimated for
contact with treated turf.

6  SEQ CHAPTER \h \r 1 .0	Aggregate Risk Assessments and Risk
Characterization

In accordance with the FQPA, the Agency must consider aggregate
pesticide exposures and risks from three major sources: food, drinking
water, and residential exposures.  In an aggregate assessment, exposures
from relevant sources are added together and compared to quantitative
estimates of hazard (e.g., a NOAEL or PAD), or the risks themselves can
be aggregated.  When aggregating exposures and risks from various
sources, the Agency considers both the route and duration of exposure. 
Fluopicolide is registered for use in residential settings as well as
for use on food; therefore, an aggregate risk was conducted which
combined average food residues with non-occupational estimates of
exposure.

6.1	Acute Aggregate Risk

 TC \l2 "7.1 Acute Aggregate Risk 

An acute aggregate assessment was not conducted because an endpoint
attributable to a single dose was not identified from the available data
for fluopicolide.

6.2	Short- and Intermediate-Term Aggregate Risks TC \l2 "7.2 Short-Term
Aggregate Risk 

All endpoints for risk assessment were based on the developmental
toxicity study in the rabbit with a NOAEL of 20 mg/kg/day.  For the
short- and intermediate- term dermal and inhalation assessments, the
chronic/oncogenicity study in rats was considered co-critical.  While
the short- and intermediate-term aggregate risk assessments share a
common endpoint, there are differences in the assessment, since the
Agency considers handler activities to be short-term in duration only. 
To assess short- and intermediate-term aggregate risks, aggregate
residential exposures (Table 6.2.1, below) are combined with average
dietary exposure estimates (Table 4.2).  Since short- and
intermediate-term aggregate risks are greater than 100, they represent
risk estimates that are below HED’s level of concern.  Short- and
intermediate-term risks are shown in Table 6.2.2, below.

Table 6.2.1  Short- and Intermediate-Term Residential Exposures for the
Fluopicolide Aggregate Risk Assessments

Population	Handler Exposure (mg/kg/day)1	Postapplication Exposure

(mg/kg/day)2	Residential Exposure

(mg/kg/day)3

Short-Term

Adult Male	0.009238

Source: Table 5.1

Garden hose-end sprayer (ST)	0.027

Source: Table 5.2

ST/IT Dermal Exposure to Treated Lawn	0.036238

Adult Female	0.009238

Source: Table 5.1

Garden hose-end sprayer (ST)	0.027

Source: Table 5.2

ST/IT Dermal Exposure to Treated Lawn	0.036238

Child 	N/A	0.043

Source: Table 5.2

ST/IT Lawn Dermal and HTM Combined Exposures 	0.043

Intermediate-Term

Adult Male	N/A	0.027

Source: Table 5.2

ST/IT Dermal Exposure to Treated Lawn	0.027

Adult Female	N/A	0.027

Source: Table 5.2

ST/IT Dermal Exposure to Treated Lawn	0.027

Child 	N/A	0.043

Source: Table 5.2

ST/IT Lawn Dermal and HTM Combined Exposures 	0.043

1  Handler exposure, which is applicable to adult populations only,
combines dermal and inhalation handler exposure.  This exposure is
included in the short-term aggregate assessment for adults only, as HED
does not believe that residential handlers will have intermediate-term
exposures.  

2  Postapplication exposure for adults, includes dermal exposure to
treated lawns.  Postapplication exposure for children combines
postapplication exposures from dermal and incidental oral (HTM) exposure
from exposure to treated lawns.  Both short- and intermediate-term
durations are appropriate for post-application exposures.  

3 Residential exposure is the sum of the handler (adults only) and post
application exposures.  

Table 6.2.2.  Short- and Intermediate-Term Aggregate Risk Calculations 

Population	NOAEL

mg/kg/day	LOC1	Max Allowable

Exposure2

mg/kg/day	Average

Food & Water

Exposure

mg/kg/day	Residential Exposure3

mg/kg/day	Aggregate MOE

(food and

residential)4

Short-Term

Adults Male	20	100	0.2	0.015395	0.036238	390

Adult Female	20	100	0.2	0.015395	0.036238	390

Child	20	100	0.2	0.025218	0.043	290

Intermediate-Term

Adults Male	20	100	0.2	0.015395	0.027	470

Adult Female	20	100	0.2	0.015395	0.027	470

Child	20	100	0.2	0.025218	0.043	290

1 UFA  = 10x (extrapolation from animal to human (interspecies); UFH =
10x potential variation in sensitivity among members of the human
population (intraspecies); FQPA SF = 1x.  10 x 10 x 1 = 100.

2 Maximum Allowable Exposure (mg/kg/day) = NOAEL/LOC = 20 mg/kg/day ÷
100 = 0.2 mg/kg/day.

3 Residential Exposure = [Oral exposure + Dermal exposure + Inhalation
Exposure], calculated by adding PDR values shown in Table 6.3.5 above. 
Residential exposures were calculated for adults (60 mg bw) and children
(15 mg bw).

4 Aggregate MOE = [NOAEL / (Avg Food & Water Exposure + Residential
Exposure)]

6.3	Long-Term Aggregate Risk TC \l2 "7.4 Long-Term Aggregate Risk 

There are no residential exposures scenarios that are anticipated to
result in long-term residential exposure.  Therefore, the long-term
(chronic) aggregate exposure and risk assessment includes risks from
exposure to food and drinking water only.  As shown in Table 4.2 of this
risk assessment, there are long-term aggregate risks of concern.  

6.4	Cancer Risk TC \l2 "7.5 Cancer Risk 

Fluopicolide has been classified as “not likely to be carcinogenic to
humans.”  As such, an estimate of cancer risk is not warranted for
fluopicolide.

7  SEQ CHAPTER \h \r 1 .0	Cumulative Risk Characterization/Assessment 

Unlike other pesticides for which EPA has followed a cumulative risk
approach based on a common mechanism of toxicity, EPA has not made a
common mechanism of toxicity finding as to fluopicolide (parent) and any
other substances.  For the purposes of this tolerance action, therefore,
EPA has not assumed that fluopicolide (parent) has a common mechanism of
toxicity with other substances. For information regarding EPA’s
efforts to determine which chemicals have a common mechanism of toxicity
and to evaluate the cumulative effects of such chemicals, see the policy
statements released by EPA’s Office of Pesticide Programs concerning
common mechanism determinations and procedures for cumulating effects
from substances found to have a common mechanism on EPA’s website at  
HYPERLINK http://www.epa.gov/pesticides/cumulative/.
http://www.epa.gov/pesticides/cumulative/. 

8.0	Occupational Exposure/Risk Pathway

D347228, K. O’Rourke, 12/13/07, ORE Assessment

D326082, K. O’Rourke, 10/9/07, ORE Assessment

8.1	Handler Exposure and Risk

There is a potential for exposure to fluopicolide during mixing,
loading, and application activities.  No chemical-specific handler
exposure data were submitted in support of this registration.  It is the
policy of the HED to use data from the Pesticide Handlers Exposure
Database (PHED) Version 1.1 as presented in PHED Surrogate Exposure
Guide (8/98) to assess handler exposures for regulatory actions when
chemical-specific monitoring data are not available (HED Science
Advisory Council for Exposure Standard Operating Procedure #7, dated
1/28/99).  

Chronic exposure is not expected for the proposed use patterns
associated with fluopicolide.  Estimated short-/intermediate-term dermal
and inhalation exposures were compared to the oral NOAEL of 20 mg/kg/day
from a rabbit developmental toxicity study in which death,
abortions/premature deliveries, decreased food consumption, and
decreased body weight gain were observed at the LOAEL of 60 mg/kg/day. 
Because this endpoint is from an oral study, the estimated dermal
exposures were adjusted by applying a 37 percent dermal absorption rate
(based on a dermal penetration study in the rat), while inhalation
toxicity was assumed to be equivalent to oral toxicity.  In addition,
this endpoint is protective of all populations, including females 13+
years old; therefore, a 60-kg body weight was used in the calculations. 
Resulting dermal and inhalation MOEs were combined into Total MOEs
because the same dose and endpoint were chosen to evaluate both routes
of exposure.  The level of concern (LOC) for occupational risk is for
margins of exposure (MOEs) <100.  

The results of the handler occupational exposure and risk assessment for
fluopicolide indicate that risks are not of concern with baseline
clothing or when chemical-resistant gloves are worn (which is required
for applicators and other handlers on the proposed label).  The total
short/intermediate-term MOEs range from 110 to 19,000; which exceed the
LOC of 100, and are not of concern.  Exposure assumptions and MOEs for
occupational handlers are summarized in Table 8.1. 

HED recognizes that it is feasible for the same individual to mix/load
and apply formulations with the groundboom sprayer; however, appropriate
data are not available in PHED for which unit exposure values for these
combined activities can be derived.  HED does not recommend simply
adding the unit exposure values for each job function because any
extrapolation error (i.e., exposure from the amount ai handled in the
study to that of a real-life application) would be magnified, leading to
greater uncertainty.  For information and characterization purposes,
even with the over-estimation uncertainty, the MOE for these combined
activities for groundboom application of fluopicolide would be above the
LOC of 100 (i.e., approximately 110). 

		



	Table 8.1.  Summary of  MOEs for Occupational Handlers of Fluopicolide

Exposure Scenario (Scenario #)	Dermal Unit Exposure

 (mg/lb ai) 1	Inhalation

Unit

Exposure

(mg/lb ai)2	Use Site	Application 

Rate 

(lb ai/A)3	Area Treated

(A/day) 4	Daily Dose

(mg/kg/day) 5	Total 

Short-/Int-term MOE 6

	Baseline	PPE

(gloves)

	Dermal	Inhalation	Baseline	PPE

(gloves)

Mixer/Loader

Mixing/ Loading Liquid for Aerial application or Chemigation	2.9	0.023
0.0012	Brassica, Bulb, Root & Tuber and Leafy Vegetables	0.13	350	0.81

0.0065 (gloves)	0.00091	25	2,700

Mixing/ Loading Liquid for Groundboom application or Chemigation	2.9	-
0.0012

0.13	80	0.19	0.00021	110	-

Applicator

Applying Sprays with Fixed-wing Aircraft	0.005	-	0.000068	Brassica,
Bulb, Root & Tuber and Leafy Vegetables	0.13	350	0.0014	0.000052	14,000
-

Applying Sprays with Open Cab Groundboom 	0.014	-	0.00074

0.13	80	0.00090	0.00013	19,000	-

Flagger

Flagging to Support Aerial Applications	0.011	-	0.00035	Brassica, Bulb,
Root & Tuber and Leafy Vegetables	0.13	350	0.0031	0.00027	6,000	-

Information in this table taken from DP Barcodes D347228 and D326082.

1 Baseline dermal unit exposure values represent long pants, long
sleeved shirts, shoes, and socks; PPE values represent the addition of
chemical-resistant gloves for the scenario in which the MOE does not
reach 100 at baseline.  Application by fixed-wing aircraft has
engineering control of enclosed cab per (ExpoSAC) Policy #006.  Values
are reported in the PHED Surrogate Exposure Guide dated August 1998.

2 Inhalation unit exposure values represent no respirator.  . 
Application by fixed-wing aircraft has engineering control of enclosed
cab per (ExpoSAC) Policy #006.  Values are reported in the PHED
Surrogate Exposure Guide dated August 1998.

3 Application rates are based on maximum values found in proposed label:
V-10161 4 SC (Reg No. 59639-RUN).

4 Daily area treated is based on the area or gallons that can be
reasonably applied in a single day for each exposure scenario of concern
based on the application method and formulation/packaging type.
(standard EPA/OPP/HED values).

5 Daily Dose (mg/kg/day) = Unit Exposure * % Absorption * Application
rate * Area treated} / 60 kg; where dermal absorption is 37% and
inhalation absorption is assumed to be 100%.

6 Short-/Intermediate-Term MOE = NOAEL (20 mg/kg/day) / (Daily Dermal
Dose + Daily Inhalation Dose).  The LOC is 100. 

8.2	Postapplication Exposure and Risk

This registration action for fluopicolide involves application to
agricultural crops.  Dermal exposure is possible for workers entering
treated areas to tend or harvest crops.  A dislodgeable foliar residue
(DFR) study was previously submitted by the registrant (MRID#: 46708641)
for use in assessing postapplication activities.  This study is
considered to be acceptable, and the data were used to estimate exposure
from activities associated with agricultural crops.  The data regression
analyses (assuming pseudo first-order kinetics) from both sites indicate
that the initial dislodgeable residue is 29% of the application rate. 
Because rainfall at the Pennsylvania site was significantly above
average during the study period, California data were used to estimate
the dissipation rate (14% per day).  

In addition to DFR, transfer coefficients (Tc) are used to relate the
residue values to activity patterns, which take place after application,
to estimate potential human exposure.  The transfer coefficients used in
this assessment are from an interim transfer coefficient guidance
document developed by HED’s Science Advisory Council for Exposure
using proprietary data from the Agricultural Re-entry Task Force (ARTF)
database (SOP# 3.1).  

The use of personal protective equipment or other types of equipment to
reduce exposures for post-application workers is not considered a viable
alternative for the regulatory process except in specialized situations.
 This is described in some detail in the Agency’s Worker Protection
Standard (40 CFR 170) and ExpoSAC Policy #010. All occupational
post-application risk estimates assessed in this document assume the
reentry workers are wearing standard agricultural clothing, including
long pants, a long-sleeve shirt, socks, and shoes.  

Postapplication MOEs were estimated for “Day 0" exposure (i.e., the
day of application).  As shown in Table 8.2., the
short-/intermediate-term MOEs are greater than 100 on the day of
application for all agricultural crops.  

The fluopicolide technical material has been classified in Toxicity
Category IV for acute dermal and primary skin irritation and Category
III for primary eye irritation.  Per the Worker Protection Standard
(WPS), a 12-hr restricted entry interval (REI) is required for chemicals
classified under Toxicity Category III/IV.  The proposed fluopicolide
label indicates an REI of 12 hrs, which is in compliance with the WPS.

Table 8.2.  Summary of Estimated Post-application MOEs for Agricultural
Crops

Crop	Application Rate

(lb ai/A) 1	DAT 2	DFR 3

(μg/cm2)	TC 4

(cm2/hr)	Activity 4	Short-/Int-

Term MOE 5

Brassica Vegetables	0.13	0	0.42	2,000	Irrigation, scouting, thinning,
weeding immature plants	480

4,000	Scouting mature plants	240

5,000	Hand harvesting, irrigation, pruning, topping, tying mature plants
190

Bulb Vegetables,

Root & Tuber Vegetables

0	0.42	300	Irrigation, scouting, thinning, weeding immature plants	3,200

1,500	Irrigation and scouting mature plants	640

2,500	Hand harvesting	380

Cucurbit & Leafy Vegetables

0	0.42	500	Irrigation, scouting, thinning, weeding immature plants	1,900

1,500	Irrigation, scouting, weeding mature plants	640

2,500	Hand harvesting, pulling, pruning, and thinning mature plants	380

Information in this table taken from DP Barcodes D347228 and D326082.

1 Maximum application rate from proposed label: V-10161 4 SC (Reg No.
59639-RUN).

2 DAT = Days after treatment needed to reach the LOC of 100; DAT 0 = The
day of treatment, after sprays have dried; assumed to be approximately
12 hours.  

3 DFR (µg/cm2) = dislodgeable foliar residues corresponding to DAT,
based on results from a chemical-specific DFR study conducted on lettuce
(MRID 46708641).

4 TC (cm2/hr) = transfer coefficients and associated activities from
ExpoSAC Policy Memo #003.1 “Agricultural Transfer Coefficients”,
8/17/2000.

5 MOE = MOE on the corresponding DAT.  MOE = NOAEL / Daily Dose.  

Daily Dose = [(TTR or DFR x  TC x 37% Dermal absorption  x  8-hr
Exposure Time)] / [(CF: 1000 µg/mg) x (60-kg Body Weight)]

Short-/intermediate-term NOAEL = 20 mg/kg/day.  The LOC is 100.

Based on the Agency's current practices, a quantitative occupational
postapplication inhalation exposure assessment was not performed for
fluopicolide at this time.  However, there are multiple potential
sources of postapplication inhalation exposure to individuals performing
postapplication activities in previously treated fields.  These
potential sources include volatilization of pesticides and resuspension
of dusts and/or particulates that contain pesticides.  The Agency sought
expert advice and input on issues related to volatilization of
pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act
Scientific Advisory Panel (SAP) in December 2009.  The Agency received
the SAP’s final report on March 2, 2010
(http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html).  The
Agency is in the process of evaluating the SAP report as well as
available postapplication inhalation exposure data generated by the
Agricultural Reentry Task Force and may, as appropriate, develop
policies and procedures, to identify the need for and, subsequently, the
way to incorporate occupational postapplication inhalation exposure into
the Agency's risk assessments.  If new policies or procedures are put
into place, the Agency may revisit the need for a quantitative
occupational postapplication inhalation exposure assessment for
fluopicolide.

Environmental Justice

Potential areas of environmental justice concerns, to the extent
possible, were considered in this human health risk assessment, in
accordance with U.S. Executive Order 12898, "Federal Actions to Address
Environmental Justice in Minority Populations and Low-Income
Populations,"   HYPERLINK
"http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf" 
http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf ).

As a part of every pesticide risk assessment, OPP considers a large
variety of consumer subgroups according to well-established procedures. 
In line with OPP policy, HED estimates risks to population subgroups
from pesticide exposures that are based on patterns of that subgroup’s
food and water consumption, and activities in and around the home that
involve pesticide use in a residential setting.  Extensive data on food
consumption patterns are compiled by the USDA under the Continuing
Survey of Food Intake by Individuals (CSFII) and are used in pesticide
risk assessments for all registered food uses of a pesticide.  These
data are analyzed and categorized by subgroups based on age, season of
the year, ethnic group, and region of the country.  Additionally, OPP is
able to assess dietary exposure to smaller, specialized subgroups and
exposure assessments are performed when conditions or circumstances
warrant.  Whenever appropriate, nondietary exposures based on home use
of pesticide products and associated risks for adult applicators and for
toddlers, youths, and adults entering or playing on treated areas
postapplication are evaluated.  Further considerations are currently in
development as OPP has committed resources and expertise to the
development of specialized software and models that consider exposure to
bystanders and farm workers as well as lifestyle and traditional dietary
patterns among specific subgroups.

Data Needs and Label Recommendations

10.1	Toxicology

The following toxicity database deficiency has been identified:

An immunotoxicity study is required.  Immunotoxicity testing. Due to the
lack of evidence of immunotoxicity for fluopicolide, the Agency
considers this to be confirmatory data and can be submitted as a
condition of registration.  

Residue Chemistry

The following residue chemistry deficiencies have been identified:

Proposed Tolerance (Section F)

The petitioner should submit a revised Section F proposing a tolerance
of 18 ppm for residues of fluopicolide per se in “Brassica, leafy
greens, subgroup 5B”. 

HED recommends that the tolerance expression for fluopicolide be revised
under 180.627(a)(1) and established under 180.627(d) to read as follows.

Tolerances are established for residues of the fungicide fluopicolide
[2,6-dichloro-N-[[3-chloro-5-(trifluoromethyl)-2-pyridinyl]methyl]benzam
ide], including its metabolites and degradates, in or on the
commodities in the table below.   Compliance with the tolerance levels
specified below is to be determined by measuring only fluopicolide
[2,6-dichloro-N-[[3-chloro-5-(trifluoromethyl)-2-pyridinyl]methyl]benzam
ide] in or on the commodity.

  SEQ CHAPTER \h \r 1 

Directions for Use

The V10161 4SC label must be amended to limit rotation only to those
crops for which there is a direct use on the label and to wheat with a
30-day PBI.   Additionally, “Do not use on varieties of turnips such
as fodder turnips intended for livestock use” should be added to the
V10161 4SC label.  Lastly, the label should be revised to specify a RTI
of 10 days for Brassica leafy greens.

The V-10162 Premix label must be amended to limit rotation only to those
crops for which there is a direct use on the label. Additionally, the
application rates in the “Crop Specific Requirements Table” should
be listed only in terms of fluid ounces per acre or the label should be
amended to show the lbs/A for both fluopicolide and propamocarb.

Storage Stability

Data are required on a representative root and tuber vegetable (tops and
roots) reflecting storage of fluopicolide and BAM for up to 47 months. 
While the Agency believes that given the demonstrated stability of
fluopicolide in/on a wide variety of crops for up to 30 months, residues
are not likely to substantially decline in root and tuber vegetables
stored longer than 30 months and up to 47 months, additional storage
stability data to confirm this is required as a condition of
registration.  

Processed Food and Feed

Since residues concentrate in wheat milled byproducts, residue data and
a tolerance are required for aspirated grain fractions.  The Agency
recommends setting the AGF tolerance at 0.07 ppm based on the wheat
processing data; however, confirmatory residue data on AGF is required. 

Occupational and Residential Exposure

No data gaps have been identified with respect to occupational and
residential exposure.

Human Studies Review

This assessment relies in part on data from studies in which adult human
subjects were intentionally exposed to a pesticide.  These studies,
listed below, have received the appropriate ethical review.

The PHED Task Force, 1998.  The Pesticide Handler Exposure Database
(PHED), Version 1.1.  Task Force members Health Canada, U.S.
Environmental Protection Agency, the California Department of Pesticide
regulation, and the American Crop Protection Association, released
August 1998.

ORETF Studies: Outdoor Residential Exposure Task Force (ORETF), April
2001.  Reviewed by HED and Health Canada.

ARTF Studies.  Agricultural Reentry Task Force (ARTF). Reviewed by HED,
ExpoSAC SOP No. 003 (May 7th, 1998 - Revised August 7th, 2000).  

Appendix A:  Toxicity Profile tc  \l 2 "A.2	Toxicity Profiles 

Table A.2.1	Acute Toxicity Profile of Fluopicolide Technical, and
Selected Metabolites and Formulations

Guideline No.	Study Type	MRID(s)	Results	Toxicity Category

870.1100	Acute oral [rat] Fluopicolide

Technical 98.3% (AE C638206)

Formulation SC 40 (AE C638206)

Formulation SC61 (AE B066752)	

46708601

46709903

46709803	

≥  2000  mg/kg (f)

LD50 ≥ 2000  mg/kg (m/f)

LD50 ≥ 2000  mg/kg (m/f)	

III

III

III

870.1100	Acute oral [rat] Metabolites

2,6-dichlorobenzamide (BAM)

1,3-chloro-5 (trifluoromethyl)

pyridine-2-carboxylic acid (PCA)	

42940201

46708602

46708603	

LD50 ≥ 1538/1144  mg/kg (m/f)

LD50 ≥ 2000/300 mg/kg (m/f)

LD50≥2000 mg/kg (m/f)	

III

II

III

870.1200	Acute dermal [rat]

Technical 97.7% (AE C638206)

Formulation SC40 (AE C638206)

Formulation SC61 (AE B066752)	

46708605

46709904

46709804	

LD50 ≥ 5000 mg/kg

LD50 ≥ 4000 mg/kg

LD50 ≥4000 mg/kg	

IV

III

III

870.1300	Acute inhalation [rat]

Technical (AE C638206)

Formulation SC40 (AE C638206)

Formulation SC61 (AE B066752)	

46708606

46709905

46709805	

LC50 ≥ 5.16 mg/L

LC50 ≥ 1.789 mg/L

LC50 ≥ 3.195 mg/L	

IV

III

IV

870.2400	Acute eye irritation [rabbit]

Technical 97.7% (AE C638206)

Formulation SC40 (AE C638206)

Formulation SC61 (AE B066752)	

46708607

46709906 46709806	

slight conjuctival irritation

chemosis/corneal opacity in both studies	

IV

III

III

870.2500	Acute dermal irritation [rabbit]

Technical 97.7% (AE C638206)

Formulation SC40 (AE C638206)

Formulation SC61 (AE B066752)	

46708650

46709907

46709807	

None (PDII = 0.00)

slight (PDII = 0.08)

slight (PDII = 0.25)	

IV

IV

IV

870.2600	Skin sensitization [guinea pig]

Technical 97.7% (AE C638206)

Formulation SC40 (AE C638206)

Formulation SC61 (AE B066752)	

46708608

46709908

46709808	

Negative (Magnusson-Kligman)

Negative (Buehler)

Negative (Modified Buehler)	

non-sensitizer

Table A.2.2	Subchronic, Chronic and Other Toxicity Profile of
Fluopicolide 

Guideline No. 	Study Type	MRID No. (year)/ Classification /Doses	Results

870.3050	28-day dietary toxicity (mouse)	46708609 (2000)

Acceptable/Guideline

M/F: 0/0, 0.95/1.19, 10.4/12.9, 100/129,  980/1242 mg/kg/day 	NOAEL =
980/1242 mg/kg/day; the limit dose).

The LOAEL was not observed.  

870.3050	28-day dietary toxicity (rat)	46708610 (2000)

Acceptable/Guideline 

M/F: 0/0, 1.8/1.8, 17.4/17.9, 174/184, and 1720/1820 mg/kg/day	NOAEL =
17.4/17.9 mg/kg/day in males/females).

The LOAEL = 174/184 mg/kg/day (M/F) based on decreased body weight gain
and food conversion in females and nephrotoxicity in males.  

870.3050	28-day dietary toxicity (rat)

AE 1344122 (Fluopicolide metabolite)	46708611 (2003)

Acceptable/Guideline 

M/F: 0/0, 1.5/1.7, 14.9/16.8, 151.6/167.1, 1495.3/1615.5 mg/kg/day	NOAEL
= 151.6/167.1 mg/kg/day.

LOAEL = 1495.3/1615.5 mg/kg/day based on decreased body weights and body
weight gains in both sexes, and nephrotoxicity in females. 

870.3050	28-day dietary toxicity (rat)

AE C657378 (a Fluopicolide metabolite)	46708612 (2003) 

Acceptable/Guideline 

M/F: 0/0, 1.6/2.1, 16.2/20.4, 159.2/230.6, and 1775.0/1930.8 mg/kg/day
NOAEL = 159.2/230.6 mg/kg/day.

LOAEL = 1775.0/1930.8 mg/kg/day based on decreases in body weight and
body weight gain (males); increased absolute (females) and relative
liver weight (both sexes) and relative kidney weight (males); increased
cholesterol (both sexes); and histopathological effects in the liver
(females), the kidneys (males), and thyroid (both sexes).

870.3050	28-day oral toxicity (dog)

	46708613 (2000)

Acceptable/Non-guideline 

0, 10, 100, 1000 mg/kg/day	NOAEL = 1000 mg/kg/day (limit dose).

LOAEL was not observed.  

870.3100

	90-Day oral toxicity (rat)	46474112 (2000)

Acceptable/guideline

M: 0, 7.4, 109, 1668 mg/kg/d

F: 0, 8.4, 119, 1673 mg/kg/day	NOAEL = 109 mg/kg/day for males; 8.4
mg/kg/day for females

LOAEL = 1668 mg/kg/day for males and 119 mg/kg/day for females based on
hypertrophy of the zona glomerulosa in the adrenal gland (M/F),
decreased cellularity of the bone marrow (M/F), and trabecular
hyperostosis of the bone joint (M)

870.3100

	90-Day oral toxicity (mouse)	46474114 (2000)

Acceptable/guideline

M/F: 0, 5.5, 53, 545 or 1092 mg/kg/day	NOAEL = 1092 mg/kg/day (M/F)

LOAEL = not identified

870.3100

	90-Day oral toxicity (mouse)	46474116 (2001)

Acceptable/guideline

M: 0, 10.4, 37.8, 161, 770 mg/kg/d

F: 0, 12.6, 52.8, 207, 965 mg/kg/day	NOAEL = 770 mg/kg/day for males;
207 mg/kg/day for females

LOAEL = not identified for males; 965 mg/kg/day for females based on
increased incidence of liver oval cell proliferation

870.3150

	90-Day oral toxicity (dog)	46474118 (2000)

Acceptable/guideline

M&F: 0, 5, 70, 1000 mg/kg/day	NOAEL = 1000 mg/kg/day (M/F)

LOAEL = not identified (M/F)

870.3200

	21/28-Day dermal toxicity (species)	46708614 (2003)

Acceptable Guideline

0, 100, 250, 500, 1000 mg/kg/day	NOAEL = 1000 mg/kg/day

LOAEL > 1000 mg/kg/day

No local or systemic toxicity observed

870.3700a

	Prenatal developmental in (rat)

Pilot study	46708615 (2000)

Acceptable/non-guideline

F: 500, 1000 mg/kg/day (GD 7-20)	NOAEL/LOAEL not determined.  Only four
animals/group. Purpose of study was to determine high-dose level for
46474120.

870.3700a

	Prenatal developmental in (rat)	46474120 (2001)

Acceptable/guideline

F: 0, 5, 60, 700 mg/kg/day (GD 7-20)	Maternal NOAEL = 60 mg/kg/day

LOAEL = 700 mg/kg/day based on decreased body weight gain

Developmental NOAEL = 60 mg/kg/day

LOAEL = 700 mg/kg/day based on delayed fetal growth and delayed
ossification

870.3700b

	Prenatal developmental in (rabbit)

Pilot study	46708616 (2000)

Acceptable/non-guideline

F: 25, 50, 100, 250, 500, or 1000 mg/kg bw/day

(GD 6-28)	Maternal NOAEL = 25 mg/kg/day

LOAEL = 50 mg/kg/day based on reduced defecation and abortion in a
single dose

Developmental NOAEL = 1000 mg/kg/day

LOAEL = not observed

870.3700b

	Prenatal developmental in (rabbit)	46474122 (2001)

Acceptable/guideline

F: 0, 5, 20, 60 mg/kg/day (GD 6-28)	Maternal NOAEL = 20 mg/kg/day

LOAEL = 60 mg/kg/day based on death, late-term abortion/premature
delivery, decreased food consumption and weight gain

Developmental NOAEL = 20 mg/kg/day

LOAEL = 60 mg/kg/day based on abortion/premature delivery, decreased
fetal body weight and crown-rump length

870.3800

	Reproduction and fertility effects

(rat)	46474124 (2003)

46474125 (additional data, 2004)

46474126 (range-finding, 2002)

Acceptable/guideline

M: 0, 7.4, 36.4, 144.6 mg/kg/d

F: 0, 8.1, 41.0, 159.7 mg/kg/day	Parental/Systemic NOAEL = 36.4/41.0
mg/kg/day (M/F)

LOAEL = 144.6/159.7 mg/kg/day (M/F) based on kidney toxicity in males
and females and decreased weight gain in females.

 NOAEL = 144.6/159.7 mg/kg/day (M/F)

LOAEL = not identified.

Offspring NOAEL = 36.4/41.0 mg/kg/day (M/F)

LOAEL = 144.6/159.7 mg/kg/day (M/F) based on decreased body weight and
weight gain.

870.4100b

	Chronic toxicity (dog)	44674128 (2002)

Acceptable/guideline

M&F: 0, 70, 300, 1000 mg/kg/day	NOAEL = 300 mg/kg/day (M); 1000
mg/kg/day (F)

LOAEL = 1000 mg/kg/day based on decreased body weight gain (M); not
identified (F)

870.4200b

	Carcinogenicity

(mouse)	46474130 (2003)

Acceptable/guideline

M: 0, 7.9, 64.5, 551.0 mg/kg/d

F: 0, 11.5, 91.9, 772.3 mg/kg/day	NOAEL = 64.5/91.9 mg/kg/day (M/F)

LOAEL = 551.0/772.3 mg/kg/day (M/F) based on decreased body weight and
weight gain and liver lesions.

no evidence of carcinogenicity

870.4300

	Chronic/ Carcinogenicity

(rat)	46474139 (2003)

Acceptable/guideline

M: 0, 2.1, 8.4, 31.5, 109.4 mg/kg/day

F: 0, 2.8, 10.8, 41.0, 142.2 mg/kg/day	NOAEL = 31.5/41.0 mg/kg/day (M/F)

LOAEL = 109.4/142.2 mg/kg/day based on decreased body weight gain (M/F)
and thyroid toxicity (M).

no evidence of carcinogenicity

870.5100 	Gene Mutation

 (Salmonella typhimurium)	46474146 (2001)

Unacceptable/guideline

1.6- 5000 µg/plate

46474202 (2001)

Acceptable/guideline

1.6- 5000 µg/plate

46474148 (2001)

Acceptable/guideline

1.6- 5000 µg/plate

46474144 (2001)

Acceptable/guideline

1.6- 5000 µg/plate

46474142 (2004)

Acceptable/guideline

AE638206 (batch mixture of  PP/241067/1 and PP/241024)

5 - 5000 µg/plate	negative (non-mutagenic) Upgradeable if purity for
test material is given. 

negative (non-mutagenic)

negative (non-mutagenic)

negative (non-mutagenic

positive (mutagenic)

870.5300 	Gene mutation

 (Chinese hamster lung cells)	46474204 (2000)

Acceptable/guideline

AE638206 (batch mixture of  PP/241067/1 and PP/241024)

1.2- 3820 µg/mL	negative (non-mutagenic)

870.5375 	Cytogenetics	46474208 (2001)

Acceptable/guideline

1.22 to 625 µg/mL

46474206 (2004)

Acceptable/guideline

AE638206 (batch mixture of PP/241067/1 and PP/241024)

3.2 to 100 µg/mL	negative for chromosome aberrations

positive for aberrations without S9 activation

870.5395

	Micronucleus

 (mouse)	46474214 (2003)

Acceptable/guideline

150, 300 or 600 mg/kg/day

46474210 (2005)

Acceptable/guideline

AE638206 (batch mixture of PP/241067/1 and PP/241024)

200, 600 or 2000 mg/kg/day

46474212 (2005)

Acceptable guideline AE C638206 (Batch No.  OP 2050046 at 2000 mg/kg/day
negative at doses up to 600 mg/kg

negative at doses up to 2000 mg/kg 

negative at dose of 2000 mg/kg

870.5550	Unscheduled DNA Synthesis

(rat hepatocytes)	42169839 (1989)

Acceptable/guideline	negative at concentration up to 300 µg/mL in
cultured rat hepatocytes 

(no OPPTS no./ FIFRA test guideline 84-2)	Other Genotoxicity 

Unscheduled DNA synthesis (rat hepatocytes)	46474216 (2000)

Acceptable/guideline

AE638206 (batch mixture of PP/241067/1 and PP/241024)

 600 or 2000 mg/kg	negative at concentrations up to 2000 mg/kg in
hepatocytes from treated rats

870.6200a 

	Acute neurotoxicity screening battery

(rat)	46474218 (2002)

46474219 (range-finding, 2002)

Acceptable/guideline

M/F: 0, 10, 100, 2000 mg/kg	NOAEL = 100 mg/kg (M/F)

LOAEL = 2000 mg/kg (M/F) based on transiently lowered body temperature.

870.6200b

	Subchronic neurotoxicity screening battery	46474221 (2002)

46474222 (positive control, 2002)

Acceptable/guideline

M: 0, 15.0, 106.6, 780.6 mg/kg/day

F: 0, 18.0, 125.2, 865.8 mg/kg/day	NOAEL = 106.6/18.0 mg/kg/day (M/F)

LOAEL = 780.6/125.2 mg/kg/day based on decreased body weight gain, food
consumption, and food efficiency.

870.6300

	Developmental neurotoxicity	None

870.7485

	Metabolism and pharmacokinetics

(rat)	46474242 (2004)-main studies

46474241 (2001)

46474244 (2003)

46474226 (2003)

46474239 (2003)

	rapid absorption, metabolism and excretion; main metabolites were
oxidative N-dealkylation cleavage products. Primary route of excretion
is fecal and urinary with little accumulation in the tissues.

870.7485

	Metabolism and pharmacokinetics

(rat)	46708632 (2002)

Acceptable Non-guideline	Most of the metabolites observed were
derivatives of AE C638206 fitting well with the prior known metabolites,
implying cysteine or N-acetyl-cysteine introduction on the phenyl ring
from gluthione conjugation, hydroxylation, or other conjugations.

870.7485

	Metabolism and pharmacokinetics

(rat)

AE C657188 (PCA)	46708636 (2002)

Acceptable Guideline	AE C657188 (PCA) showed high (87%) absorption but
low (14 – 21%) metabolism.  Excretion is mainly through the urine,
with a minor portion in the feces.

870.7485

	Metabolism and pharmacokinetics

(rat)

AE C653711 (2,6-dichloro-benzamide	46708633 (2003)

46708634 (2003)

46708635 (2003)

Acceptable Guideline	Absorption: 50-79%.  Metabolized extensively to 18
identified compounds.  The majority of the radioactivity was associated
with a mercapturic acid conjugate of hydroxyl-chlorobenzamide
(15-5-26.2%), present in the urine  Excretion mainly through urine and
feces.  

870.7600	Dermal penetration

(rat)	46708638 (2003)

Acceptable Guideline

1.43, 659 ug/cm2 skin	In vivo study

Dermal Penetration rate:  37%

870.7600	Dermal penetration

(comparative)	46708637 (2003)

Acceptable Non-guideline

1.9, 744 ug/cm2 skin	In vitro study

Rat skin dermal penetration rate  is 7.8 times greater than human skin.

Appendix B.  Tolerance Summary

The proposed tolerances should be revised to reflect the recommended
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Tolerances are established for residues of the fungicide fluopicolide
[2,6-dichloro-N-[[3-chloro-5-(trifluoromethyl)-2-pyridinyl]methyl]benzam
ide], including its metabolites and degradates, in or on the commodities
in the table below.  Compliance with the tolerance levels specified
below is to be determined by measuring only fluopicolide
[2,6-dichloro-N-[[3-chloro-5-(trifluoromethyl)-2-pyridinyl]methyl]benzam
ide] in or on the commodity.

  

Table B1. 	Tolerance Summary for Fluopicolide.

Commodity	Proposed Tolerance (ppm)	Recommended Tolerance (ppm)	Comments;
Correct Commodity Definition

Tolerances to be established under “(a) General”:

Vegetable, tuberous and corm subgroup 1C	0.02	0.02	Concurrent with
establishing this tolerance, the current tolerance on “vegetable,
tuberous and corm (except potato) subgroup 1D” should be removed.

Vegetable, tuberous and corm, subgroup 1C

Potato, processed waste	0.05	0.05

	Vegetable root, subgroup 1A	0.15	0.15	Concurrent with establishing this
tolerance, the current tolerance on “vegetable root, subgroup 1A,
except sugar beet and carrot” should be removed.

Vegetable, root, subgroup 1A

Vegetable, Brassica (Cole) leafy subgroup 5B	20	18	Brassica, leafy
greens, subgroup 5B

Tolerances to be established under (d) Indirect or inadvertent residues

Wheat, forage	0.20	0.20

	Wheat, grain	0.02	0.02

	Wheat, hay	0.50	0.50

	Wheat, milled byproducts	0.07	0.07

	Wheat, straw	0.50	0.50

	Wheat, aspirated grain fractions	0.07	0.07

	

When the new tolerances are established, the current tolerance on crop
subgroup 1D should be deleted as it will no longer required. 
Additionally, the current tolerance for the root vegetable subgroup 1A,
except sugar beet and carrot should be deleted.

New Uses on Brassica Leafy Greens, Potatoes, Sugar Beets, Carrots and
Rotational Wheat

Fluopicolide Human Health Risk Assessment

Page   PAGE  2  of   NUMPAGES  44 

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