  SEQ CHAPTER \h \r 1 

  SEQ CHAPTER \h \r 1 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

OFFICE OF              

PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES 

MEMORANDUM

DATE:  	1 NOV 2007  

SUBJECT:	Flutolanil Chronic Aggregate Dietary (Food and Drinking Water)
Exposure and Risk Assessment for the Section 3 Registration Action 

PC Code:	128975			 

		DP Number:	346322

REVIEWER:	Felecia Fort, Chemist

RRB1/Health Effects Division (7509P)

THROUGH:	Anant Parmar, Biologist

Sheila Piper, Chemist

Dietary Exposure Science Advisory Council (DESAC)

Health Effects Division (7509P)

TO:		Lisa Jones/Mary Waller, PM Team 21

		Fungicide Branch/Registration Division (7505P)

	

Executive Summary

ed using the Dietary Exposure Evaluation Model, DEEM-FCID™, Version
2.03,  which uses food consumption data from the U.S. Department of
Agriculture’s Continuing Surveys of Food Intakes by Individuals
(CSFII) from 1994-1996 and 1998.  The analysis was 

initiated to support the establishment of indirect or inadvertent
tolerances in the rotational crops, corn, soybean, cotton and wheat.
However, due to major issues pertaining to the residue analytical method
used for data analysis and the absence of storage stability to support
the lengthy sample storage durations, submitted residue data are not
acceptable to support reduced PBIs or proposed tolerances for rotated
corn and cotton.  A dietary assessment was conducted which included only
the proposed soybean, and wheat tolerances.

   

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

≤1% cPAD).   

I.	Introduction

Dietary risk assessment incorporates both exposure and toxicity of a
given pesticide.  For acute and chronic assessments, the risk is
expressed as a percentage of a maximum acceptable dose (i.e., the dose
which HED has concluded will result in no unreasonable adverse health
effects).  This dose is referred to as the population adjusted dose
(PAD).  The PAD is equivalent to point of departure (POD, NOAEL, LOAEL,
e.g.) divided by the required uncertainty or safety factors.

For acute and non-cancer chronic exposures, HED is concerned when
estimated dietary risk exceeds 100% of the PAD.  HED is generally
concerned when estimated cancer risk exceeds one in one million.
References which discuss the acute and chronic risk assessments in more
detail are available on the EPA/pesticides web site:  “Available
Information on Assessing Exposure from Pesticides, A User’s Guide,”
21-JUN-2000, web link:      HYPERLINK
"http://www.epa.gov/fedrgstr/EPA-PEST/2000/July/Day-12/6061.pdf" 
http://www.epa.gov/fedrgstr/EPA-PEST/2000/July/Day-12/6061.pdf  ; or see
SOP 99.6 (20-AUG-1999).

The most recent dietary risk assessment for flutolanil was conducted by
Manying Xue (7/24/2000, D265019).

II.	Residue Information

Tolerances are currently established for residues of flutolanil and its
metabolite converted to 2-trifluoromethyl benzoic acid and calculated as
flutolanil in/on peanuts, rice, crayfish, potatoes, milk, eggs, poultry,
beef, hogs, goats, horses and sheep (40 CFR 180.484) commodities as
follows:

Table 1.  Tolerances Currently Established

Commodity	Tolerance 

Cattle, fat1	0.10

Cattle, kidney1	1.00

Cattle, liver1	2.00

Cattle, meat byproducts1	0.05

Cattle, meat1	0.05

Egg	0.05

Goat, fat1	0.10

Goat, kidney1	1.00

Goat, liver1	2.00

Goat, meat byproducts1	0.05

Goat, meat1	0.05

Hog, fat1	0.10

Hog, kidney1	1.00

Hog, liver1	2.00

Hog, meat byproducts1	0.05

Hog, meat1	0.05

Horse, fat1	0.10

Horse, kidney1	1.00

Horse, liver1	2.00

Horse, meat byproducts1	0.05

Horse, meat1	0.05

Milk1	0.05

Peanut	0.5

Peanut, hay	15.0

Peanut meal	1.0

Potato	0.20

Potato, wet peel	0.30

Poultry (including turkeys), fat	0.05

Poultry (including turkeys), meat byproducts	0.05

Poultry (including turkeys), meat	0.05

Rice, bran	10.0

Rice, grain	7.0

Rice, hulls	25.0

Rice, straw	10.0

Sheep, fat1	0.10

Sheep, kidney1	1.00

Sheep, liver1	2.00

Sheep, meat1	0.05

Sheep, meat byproducts1	0.05

Crayfish	0.05

1.  Based on the recent reevaluation of the ruminant feeding study and
the current dietary burden, HED has determined that tolerances for milk
and ruminant meats will be deleted from the 40 CFR: 180.484, and the
tolerances for ruminant meat byproduct and other organ meats will be
changed from 0.05 ppm to 1.0 ppm. 

For the current action, HED has examined data to support the
establishment of indirect or inadvertent tolerances in the rotational
crops, corn, soybean, cotton and wheat. Due to major issues pertaining
to the residue analytical method used for data analysis and the absence
of storage stability to support the lengthy sample storage durations,
the submitted residue data were not acceptable to support reduced PBIs
or proposed tolerances for rotated corn and cotton.  These tolerances
were not included in the dietary assessment.  There are, however, no
residue chemistry issues that would preclude granting unconditional
registration for the requested amended use of flutolanil or
establishment of tolerances for indirect or inadvertent residues of
flutolanil as follow:  

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

Soybean, forage	8.0 ppm

Soybean, hay	2.5 ppm

Soybean, seed	0.20 ppm

Wheat, forage	2.5 ppm 

Wheat, grain	0.05 ppm

Wheat, hay	1.2 ppm

Wheat, straw	0.20 ppm

Wheat, bran	0.20 ppm

To support flutolanil registration, recommended tolerance levels and
DEEM( default processing factors were used to conduct the chronic
analysis.

 Drinking Water Data

The drinking water residues used in the dietary risk assessment were
provided by the Environmental Fate and Effects Division (EFED) in the
following memorandum: “Flutolanil Tier II Estimated Environmental
Concentration for Use in the Human Health Drinking Water Risk Assessment
(S. Abel, D260066, 12/13/99) and incorporated directly into this dietary
assessment.  Water residues were incorporated in the DEEM-FCID into the
food categories “water, direct, all sources” and “water, indirect,
all sources.”   

For surface water and groundwater, EDWCs were generated from PRZM-EXAMs
and from a Tier I SCI-GROW analysis, respectively.  The surface and
ground water Estimated Drinking Water Concentrations (EDWCs) shown in
Table 2 were entered as a point estimate in  the residue file editor for
DEEM-FCID.    

 Table 2.  Recommended Surface and Ground Water Concentrations ( µg/L)

Agricultural Setting	

Surface Water Concentrations	

Ground Water Concentrations



Rice (First Approximation Model)	

Peak	

Mean	

0.34

	

11.6	

3.75

	

IV.	DEEM-FCID™ Program and Consumption Information

Flutolanil acute and chronic dietary exposure assessments were conducted
using the Dietary Exposure Evaluation Model software with the Food
Commodity Intake Database DEEM-FCID™,Version 2.03 which incorporates
consumption data from USDA’s Continuing Surveys of Food Intakes by
Individuals (CSFII), 1994-1996 and 1998.  The 1994-96, 98 data are based
on the reported consumption of more than 20,000 individuals over two
non-consecutive survey days.  Foods “as consumed” (e.g., apple pie)
are linked to EPA-defined food commodities (e.g. apples, peeled fruit -
cooked; fresh or N/S; baked; or wheat flour - cooked; fresh or N/S,
baked) using publicly available recipe translation files developed
jointly by USDA/ARS and EPA.  For chronic exposure assessment,
consumption data are averaged for the entire U.S. population and within
population subgroups, but for acute exposure assessment are retained as
individual consumption events.  Based on analysis of the 1994-96, 98
CSFII consumption data, which took into account dietary patterns and
survey respondents, HED concluded that it is most appropriate to report
risk for the following population subgroups: the general U.S.
population, all infants (<1 year old), children 1-2, children 3-5,
children 6-12, youth 13-19, adults 20-49, females 13-49, and adults 50+
years old.

For chronic dietary exposure assessment, an estimate of the residue
level in each food or food-form (e.g., orange or orange juice) on the
food commodity residue list is multiplied by the average daily
consumption estimate for that food/food form to produce a residue intake
estimate.  The resulting residue intake estimate for each food/food form
is summed with the residue intake estimates for all other food/food
forms on the commodity residue list to arrive at the total average
estimated exposure.  Exposure is expressed in mg/kg body weight/day and
as a percent of the cPAD.  This procedure is performed for each
population subgroup.

V.	Toxicological Information

The doses and endpoints for dietary risk assessment were selected by the
flutolanil risk assessment team.  A summary of this information is
presented in Table 3.  flutolanil has been classified as “not likely
to be carcinogenic to humans”.  A quantitative carcinogenic dietary
analysis is not required.

The doses and toxicological endpoints selected for various exposure
scenarios are summarized below. 



Table 3  Summary of Toxicological Doses and Endpoints for Flutolanil for
Use in Dietary Exposure Risk Assessments

Exposure/

Scenario	Point of Departure	Uncertainty/FQPA Safety Factors	RfD, PAD,
Level of Concern 	Study and Toxicological Effects

Acute Dietary (All Population )	None	

No appropriate endpoint was identified in the oral toxicity studies
including developmental toxicity studies in rats and rabbits.  This risk
assessment is not required.   	N/A

Chronic Dietary (All Populations)	NOAEL= 50 mg/kg/day	UFA= 10x

UFH=10x

FQPA SF= 1x

	Chronic RfD = 0.5 mg/kg/day

cPAD = 0.5 mg/kg/day	Chronic toxicity in dog 

LOAEL = 1250 mg/kg/day based on increase of clinical toxic signs
(emesis, salivation, and soft stool), lower body weight gains and
decreased food consumption ]

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 (intraspecies).  UFH =
potential variation in sensitivity among members of the human population
(interspecies).  UFL = use of a LOAEL to extrapolate a NOAEL.  UFS = use
of a short-term study for long-term risk assessment.  UFDB = to account
for the absence of key data (i.e., lack of a critical study).  FQPA SF =
FQPA Safety Factor.  PAD = population adjusted dose (a = acute, c =
chronic).  RfD = reference dose.  

VI.	Results/Discussion 

≤1% cPAD (Table 5). 



Table 4:  Results of the Chronic Dietary Risk Analysis 

Population Subgroup	Chronic Dietary

	Dietary Exposure

(mg/kg/day)	% cPAD

General U.S. Population	0.002646	<1

All Infants (< 1 year old)	0.006003	1.2

Children 1-2 years old	0.005487	1.1

Children 3-5 years old	0.004978	1.0

Children 6-12 years old	0.003434	<1

Youth 13-19 years old	0.002447	<1

Adults 20-49 years old	0.002515	<1

Adults 50+ years old	0.001664	<1

Females 13-49 years old	0.002109	<1



VII.		List of Attachments

Chronic Food and Water Residue Input file

Chronic Results file

cc:	F. Fort (author); L. Jones

Chronic Food and Water Residue Input file

U.S. Environmental Protection Agency                                
Ver. 2.00

DEEM-FCID Chronic analysis for FLUTOLANIL                        
1994-98 data

Residue file: C:\Documents and Settings\ffort\My
Documents\Flutolanil\Dietary Assessment\Chronic Final  plus water.R98

                                                           Adjust. #2
NOT used

Analysis Date 11-02-2007             Residue file dated:
11-02-2007/16:13:37/8

Reference dose (RfD) = 0.5 mg/kg bw/day

------------------------------------------------------------------------
--------

Food Crop                                       Residue      
Adj.Factors

EPA Code  Grp  Food Name                          (ppm)       

                                                             #1        
#2 

-------- ---- -------------------------------   ---------- ------    
------

21000460 M    Beef, meat byproducts              1.000000   1.000     
1.000   

21000461 M    Beef, meat byproducts-babyfood     1.000000   1.000     
1.000   

21000470 M    Beef, fat                          0.100000   1.000     
1.000   

21000471 M    Beef,fat-babyfood                  0.100000   1.000     
1.000   

21000480 M    Beef, kidney                       1.000000   1.000     
1.000   

21000490 M    Beef, liver                        2.000000   1.000     
1.000   

21000491 M    Beef, liver-babyfood               2.000000   1.000     
1.000   

40000930 P    Chicken, meat                      0.050000   1.000     
1.000   

40000931 P    Chicken, meat-babyfood             0.050000   1.000     
1.000   

40000940 P    Chicken, liver                     0.050000   1.000     
1.000   

40000950 P    Chicken, meat byproducts           0.050000   1.000     
1.000   

40000951 P    Chicken, meat byproducts-babyfoo   0.050000   1.000     
1.000   

40000960 P    Chicken, fat                       0.050000   1.000     
1.000   

40000961 P    Chicken, fat-babyfood              0.050000   1.000     
1.000   

40000970 P    Chicken, skin                      0.050000   1.000     
1.000   

40000971 P    Chicken, skin-babyfood             0.050000   1.000     
1.000   

70001450 P    Egg, whole                         0.050000   1.000     
1.000   

70001451 P    Egg, whole-babyfood                0.050000   1.000     
1.000   

70001460 P    Egg, white                         0.050000   1.000     
1.000   

70001461 P    Egg, white (solids)-babyfood       0.050000   1.000     
1.000   

70001470 P    Egg, yolk                          0.050000   1.000     
1.000   

70001471 P    Egg, yolk-babyfood                 0.050000   1.000     
1.000   

80001620 F    Fish-shellfish, mollusc            0.050000   1.000     
1.000   

23001700 M    Goat, meat byproducts              1.000000   1.000     
1.000   

23001710 M    Goat, fat                          0.100000   1.000     
1.000   

23001720 M    Goat, kidney                       1.000000   1.000     
1.000   

23001730 M    Goat, liver                        2.000000   1.000     
1.000   

95002630 O    Peanut                             0.500000   1.000     
1.000   

95002640 O    Peanut, butter                     0.500000   1.800     
1.000   

95002650 O    Peanut, oil                        0.500000   1.000     
1.000   

25002910 M    Pork, skin                         0.100000   1.000     
1.000   

25002920 M    Pork, meat byproducts              1.000000   1.000     
1.000   

25002921 M    Pork, meat byproducts-babyfood     1.000000   1.000     
1.000   

25002930 M    Pork, fat                          0.100000   1.000     
1.000   

25002931 M    Pork, fat-babyfood                 0.100000   1.000     
1.000   

25002940 M    Pork, kidney                       1.000000   1.000     
1.000   

25002950 M    Pork, liver                        2.000000   1.000     
1.000   

01032960 1C   Potato, chips                      0.200000   1.000     
1.000   

01032970 1C   Potato, dry (granules/ flakes)     0.200000   6.500     
1.000   

01032971 1C   Potato, dry (granules/ flakes)-b   0.200000   6.500     
1.000   

01032980 1C   Potato, flour                      0.200000   1.000     
1.000   

01032981 1C   Potato, flour-babyfood             0.200000   1.000     
1.000   

01032990 1C   Potato, tuber, w/peel              0.200000   1.000     
1.000   

01032991 1C   Potato, tuber, w/peel-babyfood     0.200000   1.000     
1.000   

01033000 1C   Potato, tuber, w/o peel            0.200000   1.000     
1.000   

01033001 1C   Potato, tuber, w/o peel-babyfood   0.200000   1.000     
1.000   

60003010 P    Poultry, other, meat               0.050000   1.000     
1.000   

60003020 P    Poultry, other, liver              0.050000   1.000     
1.000   

60003030 P    Poultry, other, meat byproducts    0.050000   1.000     
1.000   

60003040 P    Poultry, other, fat                0.050000   1.000     
1.000   

60003050 P    Poultry, other, skin               0.050000   1.000     
1.000   

15003230 15   Rice, white                        7.000000   1.000     
1.000   

15003231 15   Rice, white-babyfood               7.000000   1.000     
1.000   

15003240 15   Rice, brown                        7.000000   1.000     
1.000   

15003241 15   Rice, brown-babyfood               7.000000   1.000     
1.000   

15003250 15   Rice, flour                        7.000000   1.000     
1.000   

15003251 15   Rice, flour-babyfood               7.000000   1.000     
1.000   

15003260 15   Rice, bran                        10.000000   1.000     
1.000   

15003261 15   Rice, bran-babyfood               10.000000   1.000     
1.000   

26003400 M    Sheep, meat byproducts             1.000000   1.000     
1.000   

26003410 M    Sheep, fat                         0.100000   1.000     
1.000   

26003411 M    Sheep, fat-babyfood                0.100000   1.000     
1.000   

26003420 M    Sheep, kidney                      1.000000   1.000     
1.000   

26003430 M    Sheep, liver                       2.000000   1.000     
1.000   

06003470 6    Soybean, seed                      0.200000   1.000     
1.000   

06003480 6    Soybean, flour                     0.200000   1.000     
1.000   

06003481 6    Soybean, flour-babyfood            0.200000   1.000     
1.000   

06003490 6    Soybean, soy milk                  0.200000   1.000     
1.000   

06003491 6    Soybean, soy milk-babyfood or in   0.200000   1.000     
1.000   

06003500 6    Soybean, oil                       0.200000   1.000     
1.000   

06003501 6    Soybean, oil-babyfood              0.200000   1.000     
1.000   

50003820 P    Turkey, meat                       0.050000   1.000     
1.000   

50003821 P    Turkey, meat-babyfood              0.050000   1.000     
1.000   

50003830 P    Turkey, liver                      0.050000   1.000     
1.000   

50003831 P    Turkey, liver-babyfood             0.050000   1.000     
1.000   

50003840 P    Turkey, meat byproducts            0.050000   1.000     
1.000   

50003841 P    Turkey, meat byproducts-babyfood   0.050000   1.000     
1.000   

50003850 P    Turkey, fat                        0.050000   1.000     
1.000   

50003851 P    Turkey, fat-babyfood               0.050000   1.000     
1.000   

50003860 P    Turkey, skin                       0.050000   1.000     
1.000   

50003861 P    Turkey, skin-babyfood              0.050000   1.000     
1.000   

86010000 O    Water, direct, all sources         0.003750   1.000     
1.000   

86020000 O    Water, indirect, all sources       0.003750   1.000     
1.000   

15004010 15   Wheat, grain                       0.050000   1.000     
1.000   

15004011 15   Wheat, grain-babyfood              0.050000   1.000     
1.000   

15004020 15   Wheat, flour                       0.050000   1.000     
1.000   

15004021 15   Wheat, flour-babyfood              0.050000   1.000     
1.000   

15004030 15   Wheat, germ                        0.050000   1.000     
1.000   

15004040 15   Wheat, bran                        0.200000   1.000     
1.000   



Chronic Results file

U.S. Environmental Protection Agency                                
Ver. 2.00

DEEM-FCID Chronic analysis for FLUTOLANIL                       (1994-98
data)

Residue file name: C:\Documents and Settings\ffort\My
Documents\Flutolanil\Dietary Assessment\Chronic Final  plus water.R98

                                                 Adjustment factor #2
NOT used.

Analysis Date 11-02-2007/16:14:26     Residue file dated:
11-02-2007/16:13:37/8

Reference dose (RfD, Chronic) = .5 mg/kg bw/day

========================================================================
=======

                    Total exposure by population subgroup

------------------------------------------------------------------------
-------

                                                    Total Exposure

                                        
-----------------------------------

          Population                         mg/kg             Percent
of   

           Subgroup                       body wt/day             Rfd   
   

--------------------------------------   -------------      
---------------

U.S. Population (total)                     0.002646                
0.5%

U.S. Population (spring season)             0.002681                
0.5%

U.S. Population (summer season)             0.002719                
0.5%

U.S. Population (autumn season)             0.002582                
0.5%

U.S. Population (winter season)             0.002604                
0.5%

Northeast region                            0.003043                
0.6%

Midwest region                              0.002095   
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Non-hispanic whites                         0.001938                
0.4%

Non-hispanic blacks                         0.002799                
0.6%

Non-hisp/non-white/non-black                0.009918                
2.0%

All infants (< 1 year)                      0.006003                
1.2%

Nursing infants                             0.003665                
0.7%

Non-nursing infants                         0.006891                
1.4%

Children 1-6  yrs                           0.005061                
1.0%

Children 7-12 yrs                           0.003249                
0.6%

Females 13-19 (not preg or nursing)         0.001976                
0.4%

Females 20+ (not preg or nursing)           0.001832                
0.4%

Females 13-50 yrs                           0.002290                
0.5%

Females 13+ (preg/not nursing)              0.003065                
0.6%

Females 13+ (nursing)                       0.002610                
0.5%

Males 13-19 yrs                             0.002884                
0.6%

Males 20+ yrs                               0.002582                
0.5%

Seniors 55+                                 0.001572                
0.3%

Children 1-2 yrs                            0.005487                
1.1%

Children 3-5 yrs                            0.004978                
1.0%

Children 6-12 yrs                           0.003434                
0.7%

Youth 13-19 yrs                             0.002447                
0.5%

Adults 20-49 yrs                            0.002515                
0.5%

Adults 50+ yrs                              0.001664                
0.3%

Females 13-49 yrs                           0.002109                
0.4%

------------------------------------------------------------------------
-------

Flutolanil	Dietary Exposure and Risk Assessment	DP Number: 346322	

PC Code:  128975		

________________________________________________________________________
______________

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