UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

OFFICE OF

PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

MEMORANDUM

DATE:  	November 8, 2007

SUBJECT:	Flonicamid Chronic Aggregate Dietary (Food and Drinking Water) Exposure and Risk Assessments for an IR-4 Section 3 Registration Action on Root Vegetables (Except Sugar Beet; Subgroup 1B), Tuberous and Corm Vegetables (Subgroup 1C), Leafy Brassica Greens (Subgroup 5B), Radish Tops, Turnip Greens, Hops, Dried Cones, and Okra.  PP# 6E7081.

PC Code:		128016			Decision Number: 368509

DP Number:		343466

Petition Number:	6E7081

REVIEWER:	Amelia M. Acierto, Chemist

Registration Action Branch 3/HED (7509P)

THROUGH:   Sheila Piper, Chemist

		Douglas Dotson, Chemist

Dietary Exposure Science Advisory Council (DESAC)

Health Effects Division (7509P)

Paula Deschamp, Chief

Registration Action Branch 3

Health Effects Division (7509P)

TO:		Sheila Piper, Risk Assessor

Chemistry & Exposure Branch

Health Effects Division (7509P)

Executive Summary

Chronic aggregate dietary (food and drinking water) exposure and risk assessments were conducted using the Dietary Exposure Evaluation Model (DEEM-FCID(, Version 2.03), which uses food consumption data from the USDA’s Continuing Surveys of Food Intakes by Individuals (CSFII) from 1994-1996 and 1998.  In addition to residues in/on food items, the assessment also addresses potential residues in drinking water.  In this analysis the chronic dietary exposure and risk estimates resulting from food and water intake were determined for the general U.S. population and various population subgroups.  Flonicamid has no acute endpoint and has been determined to be “not a carcinogen;” therefore only a chronic analysis was performed to support a petition for tolerances in conjunction with an IR-4 petition for a Section 3 registration for the new uses of flonicamid in/on vegetable, root crop (except sugar beet, subgroup 1B), radish, tops, tuberous and corm vegetable (subgroup 1C), Brassica, leafy greens

(subgroup 5B), turnip (greens), hop, dried cones, and okra.  Tolerances have already been established under 40 CFR 180.613 on cotton, cucurbit vegetables, fruiting vegetables, leafy vegetables (group 4 except Brassica, except spinach), spinach, pome fruit (group 11), potato, stone fruit (group 12), head and stem Brassica (subgroup 5A) and mustard greens.

Chronic Dietary Exposure Results and Characterization

A chronic dietary (food and drinking water) exposure assessment was conducted for the proposed commodities, registered commodities and drinking water.  Except for water, a conservative unrefined assessment was conducted.  The residue levels used in the assessment were the tolerance levels recommended by HED for the new commodities, the tolerance levels established under 40 CFR.§180.613 for registered crops (head and stem Brassica, cotton, cucurbit vegetable, fruiting vegetable, leafy vegetable, mustard greens, potato, pome fruit, spinach and stone fruit),  and revised tolerance levels for livestock commodities.

Estimated concentrations of 1.5 ppb (1.5 x 10-3 ppm) for the 1 in 10 year annual mean concentration of flonicamid in drinking water from the proposed uses were provided by EFED and incorporated directly into the chronic assessment.  A Tier II drinking water assessment for the proposed uses was performed using PRZM/EXAMS modeling with index reservoir (IR) scenarios and percent crop area (PCA) adjustment factors.

The chronic dietary (food and drinking water) exposure to flonicamid is below HED’s level of concern for the general U.S. population and all population subgroups.  The chronic dietary exposure estimates are 10% cPAD for the general U.S. population, 15% cPAD for all infants (<1 year old), and 23% cPAD for children 1-2 years old, the most highly exposed population subgroup.

Acute Dietary Exposure Results and Characterization

An acute dietary risk assessment was not performed as flonicamid has no acute toxicological endpoint.

Cancer Dietary Exposure Results and Characterization

A cancer dietary assessment was not conducted as flonicamid has been determined to be “not a carcinogen.”

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 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 flonicamid was conducted by Amelia Acierto

(26-April-2005, DP Number 315611).

II.	Residue Information

Flonicamid Use:

Flonicamid is a Group 9C insecticide (selective feeding blocker) registered for the control of a variety of aphid pests and the suppression of a variety of non-aphid pests.  Tolerances for registered commodities can be found in 40 CFR.§180.613.  The tolerances that are currently being recommended are listed in Table 1, below.    The residue of concern for plants are parent flonicamid and its major metabolites TFNA-AM, TFNA and TFNG; in ruminants are parent and its metabolites TFNA-AM and TFNA.

Residue Data used for Chronic Assessments:

The residue levels used in the chronic assessment were the established tolerance levels for plant commodities established under 40 CFR §180.613 and the tolerance levels based on the crop trials for the proposed crops.  Most of the livestock commodity tolerances are being increased because all regulated residues are going to be included in the tolerances.  See Table 1, below for the increased livestock commodity tolerances.

Estimated concentrations of flonicamid in drinking water from the proposed uses were provided by EFED and incorporated directly into the chronic assessment.

The assessments used 100% crop treated.

Table 1. 	Tolerance Summary for Flonicamid

Commodity or Subgroup	Proposed Tolerance (ppm)	Established Tolerance (ppm)	Recommended Tolerance (ppm)	Comments; Correct Commodity Definition

Tolerances for combined residues of flonicamid and its metabolites TFNA, TFNA-AM, and TFNG

[40 CFR 180.613(a)(1)]:

Brassica, leafy greens, subgroup 5B	16	--	16

	Hop, dried cones	7.0	--	7.0

	Mustard greens	--	11	16	Residues in/on mustard greens will be covered by the tolerance for leafy Brassica green, subgroup 5B.

Okra	0.4	--	0.40

	Potato

0.20	0.20	Residues in/on potato will be covered by the tolerance for tuberous and corm vegetables, subgroup 1C.

Radish, tops	16	--	16	Residues will be covered by the tolerance for leafy Brassica green, subgroup 5B.

Turnip, greens	16	--	16

	Vegetable, root, except sugar beet, subgroup 1B	0.45	--	0.60 Recommended tolerance based on crop field trial data

Vegetable, tuberous and corm, subgroup 1C	0.2	--	0.20

	Tolerances for combined residues of flonicamid and its metabolites TFNA-AM and TFNA in/on livestock commodities [40 CFR 180.613(a)(2)]:

Cattle, fat	--	0.02	0.03	Increased tolerances are needed to reflect combined limits of quantitation for all regulated residues.

Cattle, meat	--	0.05	0.08

	Cattle, meat byproducts	--	0.08	0.08	No change needed.

Egg	--	0.03	0.04	An increased tolerance is needed to account for all regulated residues.

Goat, fat	--	0.02	0.03	Increased tolerances are needed to reflect combined limits of quantitation for all regulated residues.

Goat, meat	--	0.05	0.08

	Goat, meat byproducts	--	0.08	0.08	No change needed.

Horse, fat	--	0.02	0.03	Increased tolerances are needed to reflect combined limits of quantitation for all regulated residues.

Horse, meat	--	0.05	0.08

	Horse, meat byproducts	--	0.08	0.08	No change needed.

Milk	--	0.02	0.03	Increased tolerances are needed to reflect combined limits of quantitation for all regulated residues.

Poultry, fat	--	0.02	0.03

	Poultry, meat	--	0.02	0.03

	Poultry, meat byproducts	--	0.02	0.03

	Sheep, fat	--	0.02	0.03

	Sheep, meat	--	0.05	0.08

	Sheep, meat byproducts	--	0.08	0.08	No change needed.

Processing Factors:

Separate tolerances were established for dried potatoes, tomato paste, and tomato puree based on processing studies.  The adjustment factor #1 was set to 1.0 for these commodities; the DEEM default processing factors were used for the other processed commodities for which default processing factors are available.

III.  Drinking Water

The drinking water residues used in the dietary risk assessment were provided by the Environmental Fate and Effects Division (EFED) in the following memorandum: “Drinking Water  Assessment for  the IR-4 New Uses of Flonicamid on Brassica, Hops, Tubulars, and Okra. Including The Flonicamid Degradation Products (TFNG, TFNA, TFNA-OH, TFNA-AM and TFNG-AM).”   Water residues were incorporated in the DEEM-FCID into the food categories “water, direct, all sources” and “water, indirect, all sources.”

No monitoring data of flonicamid were available to the Environmental Fate and Effects Division (EFED).  The estimated drinking water concentrations from surface water sources were calculated using the Tier II PRZM (Pesticide Root Zone Model) and EXAMS (Exposure Analysis Modeling System).  PRIZM is used to simulate pesticide transport as a result of runoff and erosion from an agricultural field and EXAMS estimates environmental fate and transport of pesticides in surface water.  The values generated by the models for drinking water were multiplied by a national crop area factor (PCA), which accounts for the fact that it is unlikely for any basin to be completely planted to agricultural crops.  Ground water concentrations were estimated using the Tier I SCI-GROW Model.  Flonicamid may be applied by aerial or ground as per the labels for this product.   This memo only addresses the estimations of parent flonicamid and its major metabolites, TFNG, TFNA, TFNA-OH, TFNA-AM and TFNG-AM.

Based on modeling results, the estimated drinking water (surface water) concentrations of combined residues of flonicamid and its degradation products (based on three aerial applications at the rate of 0.089 lb ai/acre and the values adjusted with PCA factor of 0.87) are:

9.8 µg /L for the 1 in 10 year annual peak concentration (acute) -  Based on the Florida carrot scenario.

1.5 µg /L for the 1 in 10 year annual mean concentration (non-cancer chronic)- Based on the California lettuce and Maine potato scenario.

0.97µg /L for the 30 year annual mean concentration (cancer chronic) -  Based on the Idaho potato scenario.

Both the acute and chronic estimated concentrations for flonicamid in ground water using the SCIGROW (version 2.3) Model are 1.32 x 10-3 µg/L (ppb) for the combined residues.

In general, the linked PRZM/EXAMS  Model produces estimated aquatic concentrations that are expected to be exceeded once within a 10-year period.

The model and its description are available at the EPA internet site:   HYPERLINK "http://www.epa.gov/oppefed1/models/water/"  http://www.epa.gov/oppefed1/models/water/ .

IV.	DEEM-FCID™ Program and Consumption Information

Flonicamid chronic dietary exposure assessment wase 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

Toxicological Endpoints and Doses for Chronic Dietary Risk Assessment

The toxicity database for flonicamid was evaluated by HED's Registration Action Branch III's Toxicology Team on 9/30/2004.  The Toxicology Team at that meeting selected endpoints and evaluated for FQPA concerns the potential hazard and exposure data for flonicamid and determined that there was no need for an additional safety factor for the protection of infants and children.  The Cancer Assessment Review Committee met on 1/5/2005.  The findings of those meetings, as related to dietary exposure, are summarized in Table 2.  Flonicamid is classified to be category “Suggestive Evidence of Carcinogenicity, but Not Sufficient to Assess Human Carcinogenic Potential,” according to the EPA Draft Guidelines for Carcinogen Risk Assessment dated July, 1999; therefore, a cancer assessment is not necessary.

Table 2.  Summary of Dose and Toxicological Endpoint Selection Relative to Use in Dietary Human Health Risk Assessment for Flonicamid

Exposure

Scenario

Dose (mg/kg/day)

UF

FQPA Safety Factor and Level of Concern for Risk Assessment

Endpoint for Risk Assessment

Acute Dietary

general population including infants and children

N/A

N/A

N/A.

Chronic Dietary

(All populations)

NOAEL= 4.0 mg/kg/day

UF = 100

cPAD = 0.04 mg/kg/day

FQPA SF = 1x

cPAD = Chronic RfD

               FQPA SF

           = 0.04 mg/kg/day

2-Gen reproduction study in the rat.  Parental LOAEL = 22 mg/kg/day based on increased kidney weights, kidney hyaline deposition, increased blood serum LH (F1 females).

Cancer (oral, dermal, inhalation)

Classified as "Suggestive Evidence of Carcinogenicity, but Not Sufficient to Assess Human Carcinogenic Potential"

N/A

N/A

UF = uncertainty factor, FQPA SF = Special FQPA safety factor, NOEL = no observed adverse effect level, LOAEL = lowest observed adverse effect level, cPAD = chronic populatio, adjusted dose, Rfd = reference dose, N/A = not applicable.

VI.	Results/Discussion

 is concerned when dietary risk exceeds 100% of the PAD.  The DEEM-FCID™ analyses estimate the dietary exposure of the U.S. population and various population subgroups.  The results reported in Table 3 below are for the general U.S. Population, all infants (<1 year old), children 1-2, children 3-5, children 6-12, youth 13-19, females 13-49, adults 20-49, and adults 50+ years.

Results of Chronic Dietary (Food and Drinking Water) Exposure Analysis

The results of the chronic dietary (food and drinking water) exposure analysis are reported in Table 3 below.

The chronic dietary (food and drinking water) exposure to flonicamid is below HED’s level of concern for the general U.S. population and all population subgroups.  The chronic dietary exposure estimates are 10% cPAD for the general U.S. population and 15% cPAD for all infants (<1 year old), and 23% cPAD for children 1-2 years old, the most highly exposed population subgroup.

Table 3.   Summary of Dietary (Food and Drinking Water) Exposure and Risk for Flonicamid

Population Subgroup

cPAD (mg/kg/day)

Exposure (mg/kg/day)

% cPAD

DEEM-FCID

DEEM-FCID

General U.S. Population

0.04

0.004095	10

All Infants (< 1 year old)

0.04

0.006087	15

Children 1-2 years old

0.04

0.009070	23

Children 3-5 years old

0.04

0.007205	18

Children 6-12 years old

0.04

0.004483	11

Youth 13-19 years old

0.04

0.003280	8

Adults 20-49 years old

0.04

0.003513	9

Females 13-49 years old

0.04

0.003504	9

Adults 50+ years old

0.04

0.003978	10

VII.	Characterization of Inputs/Outputs

The chronic dietary exposure analysis is a conservative one.  As a result, HED is confident that exposure is not underestimated to the U.S. population or any population subgroup.  Further refinements could be made; however, they are not necessary at the present time.

VIII.	 Conclusions

The chronic dietary exposure assessment was conducted for the proposed uses on root vegetables (except sugar beet; subgroup 1B), tuberous and corm vegetables (subgroup 1C), leafy Brassica greens (subgroup 5B), turnip greens, hops, dried cones, and okra and drinking water.  A conservative assessment was conducted.  Estimated concentrations of flonicamid in drinking water from the proposed uses were provided by EFED and incorporated directly into the chronic assessments.

The chronic dietary (food and drinking water) exposure to flonicamid is below HED’s level of concern for the general U.S. population and all population subgroups.  The chronic dietary exposure estimates are 10% cPAD for the general U.S. population and 15% cPAD for all infants (<1 year old), and 23% cPAD for children 1-2 years old, the most highly exposed population subgroup.

IX.		List of Attachments

#1: DEEM(-FCID Chronic Residue Input File.

#2: DEEM(-FCID Chronic Results.

Attachment 1.  DEEM(-FCID Chronic Residue Input File.

Filename: C:\Documents and Settings\aacierto\Desktop\Flonicamid.DEEMr\FLONICAMID.R98

Chemical: FLONICAMID

RfD(Chronic): .04 mg/kg bw/day  NOEL(Chronic): 4 mg/kg bw/day

RfD(Acute): 0 mg/kg bw/day  NOEL(Acute):  0 mg/kg bw/day

Date created/last modified: 11-16-2007/14:10:38/8          Program ver. 2.03

Comment: CHRONIC ONLY

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

  EPA    Crop                                   Def Res     Adj.Factors   Comment

  Code    Grp  Commodity Name                    (ppm)       #1    #2

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

04010050 4A   Amaranth, leafy                    4.000000   1.000  1.000

11000070 11   Apple, fruit with peel             0.200000   1.000  1.000

11000080 11   Apple, peeled fruit                0.200000   1.000  1.000

11000081 11   Apple, peeled fruit-babyfood       0.200000   1.000  1.000

11000090 11   Apple, dried                       0.200000   8.000  1.000

11000091 11   Apple, dried-babyfood              0.200000   8.000  1.000

11000100 11   Apple, juice                       0.200000   1.300  1.000

11000101 11   Apple, juice-babyfood              0.200000   1.300  1.000

11000110 11   Apple, sauce                       0.200000   1.000  1.000

11000111 11   Apple, sauce-babyfood              0.200000   1.000  1.000

12000120 12   Apricot                            0.600000   1.000  1.000

12000121 12   Apricot-babyfood                   0.600000   1.000  1.000

12000130 12   Apricot, dried                     0.600000   6.000  1.000

12000140 12   Apricot, juice                     0.600000   1.000  1.000

12000141 12   Apricot, juice-babyfood            0.600000   1.000  1.000

01030150 1CD  Arrowroot, flour                   0.200000   1.000  1.000

01030151 1CD  Arrowroot, flour-babyfood          0.200000   1.000  1.000

01030170 1CD  Artichoke, Jerusalem               0.200000   1.000  1.000

04010180 4A   Arugula                            4.000000   1.000  1.000

09020210 9B   Balsam pear                        0.400000   1.000  1.000

21000440 M    Beef, meat                         0.080000   1.000  1.000

21000441 M    Beef, meat-babyfood                0.080000   1.000  1.000

21000450 M    Beef, meat, dried                  0.080000   1.920  1.000

21000460 M    Beef, meat byproducts              0.080000   1.000  1.000

21000461 M    Beef, meat byproducts-babyfood     0.080000   1.000  1.000

21000470 M    Beef, fat                          0.030000   1.000  1.000

21000471 M    Beef,fat-babyfood                  0.030000   1.000  1.000

21000480 M    Beef, kidney                       0.080000   1.000  1.000

21000490 M    Beef, liver                        0.080000   1.000  1.000

21000491 M    Beef, liver-babyfood               0.080000   1.000  1.000

01010500 1AB  Beet, garden, roots                0.600000   1.000  1.000

01010501 1AB  Beet, garden, roots-babyfood       0.600000   1.000  1.000

05010610 5A   Broccoli                           1.500000   1.000  1.000

05010611 5A   Broccoli-babyfood                  1.500000   1.000  1.000

05010620 5A   Broccoli, Chinese                  1.500000   1.000  1.000

05020630 5B   Broccoli raab                     16.000000   1.000  1.000

05010640 5A   Brussels sprouts                   1.500000   1.000  1.000

01010670 1AB  Burdock                            0.600000   1.000  1.000

05010690 5A   Cabbage                            1.500000   1.000  1.000

05020700 5B   Cabbage, Chinese, bok choy        16.000000   1.000  1.000

05010710 5A   Cabbage, Chinese, napa             1.500000   1.000  1.000

05010720 5A   Cabbage, Chinese, mustard          1.500000   1.000  1.000

09010750 9A   Cantaloupe                         0.400000   1.000  1.000

04020760 4B   Cardoon                            4.000000   1.000  1.000

01010780 1AB  Carrot                             0.600000   1.000  1.000

01010781 1AB  Carrot-babyfood                    0.600000   1.000  1.000

01010790 1AB  Carrot, juice                      0.600000   1.000  1.000

09010800 9A   Casaba                             0.400000   1.000  1.000

01030820 1CD  Cassava                            0.200000   1.000  1.000

01030821 1CD  Cassava-babyfood                   0.200000   1.000  1.000

05010830 5A   Cauliflower                        1.500000   1.000  1.000

01010840 1AB  Celeriac                           0.600000   1.000  1.000

04020850 4B   Celery                             4.000000   1.000  1.000

04020851 4B   Celery-babyfood                    4.000000   1.000  1.000

04020860 4B   Celery, juice                      4.000000   1.000  1.000

04020870 4B   Celtuce                            4.000000   1.000  1.000

09020880 9B   Chayote, fruit                     0.400000   1.000  1.000

12000900 12   Cherry                             0.600000   1.000  1.000

12000901 12   Cherry-babyfood                    0.600000   1.000  1.000

12000910 12   Cherry, juice                      0.600000   1.500  1.000

12000911 12   Cherry, juice-babyfood             0.600000   1.500  1.000

40000930 P    Chicken, meat                      0.030000   1.000  1.000

40000931 P    Chicken, meat-babyfood             0.030000   1.000  1.000

40000940 P    Chicken, liver                     0.030000   1.000  1.000

40000950 P    Chicken, meat byproducts           0.030000   1.000  1.000

40000951 P    Chicken, meat byproducts-babyfoo   0.030000   1.000  1.000

40000960 P    Chicken, fat                       0.030000   1.000  1.000

40000961 P    Chicken, fat-babyfood              0.030000   1.000  1.000

40000970 P    Chicken, skin                      0.030000   1.000  1.000

40000971 P    Chicken, skin-babyfood             0.030000   1.000  1.000

01011000 1AB  Chicory, roots                     0.600000   1.000  1.000

09021020 9B   Chinese waxgourd                   0.400000   1.000  1.000

04011040 4A   Chrysanthemum, garland             4.000000   1.000  1.000

05021170 5B   Collards                          16.000000   1.000  1.000

95001280 O    Cottonseed, oil                    0.500000   1.000  1.000

95001281 O    Cottonseed, oil-babyfood           0.500000   1.000  1.000

11001290 11   Crabapple                          0.200000   1.000  1.000

04011330 4A   Cress, garden                      4.000000   1.000  1.000

04011340 4A   Cress, upland                      4.000000   1.000  1.000

09021350 9B   Cucumber                           0.400000   1.000  1.000

04011380 4A   Dandelion, leaves                  4.000000   1.000  1.000

01031390 1CD  Dasheen, corm                      0.200000   1.000  1.000

70001450 P    Egg, whole                         0.040000   1.000  1.000

70001451 P    Egg, whole-babyfood                0.040000   1.000  1.000

70001460 P    Egg, white                         0.040000   1.000  1.000

70001461 P    Egg, white (solids)-babyfood       0.040000   1.000  1.000

70001470 P    Egg, yolk                          0.040000   1.000  1.000

70001471 P    Egg, yolk-babyfood                 0.040000   1.000  1.000

08001480 8    Eggplant                           0.400000   1.000  1.000

04011500 4A   Endive                             4.000000   1.000  1.000

04021520 4B   Fennel, Florence                   4.000000   1.000  1.000

01031660 1CD  Ginger                             0.200000   1.000  1.000

01031661 1CD  Ginger-babyfood                    0.200000   1.000  1.000

01031670 1CD  Ginger, dried                      0.200000   1.000  1.000

01011680 1AB  Ginseng, dried                     0.600000   1.000  1.000

23001690 M    Goat, meat                         0.080000   1.000  1.000

23001700 M    Goat, meat byproducts              0.080000   1.000  1.000

23001710 M    Goat, fat                          0.030000   1.000  1.000

23001720 M    Goat, kidney                       0.080000   1.000  1.000

23001730 M    Goat, liver                        0.080000   1.000  1.000

09011870 9A   Honeydew melon                     0.400000   1.000  1.000

95001880 O    Hop                                7.000000   1.000  1.000

24001890 M    Horse, meat                        0.080000   1.000  1.000

01011900 1AB  Horseradish                        0.600000   1.000  1.000

05021940 5B   Kale                              16.000000   1.000  1.000

05011960 5A   Kohlrabi                           1.500000   1.000  1.000

04012040 4A   Lettuce, head                      4.000000   1.000  1.000

04012050 4A   Lettuce, leaf                      4.000000   1.000  1.000

11002100 11   Loquat                             0.200000   1.000  1.000

27002220 D    Milk, fat                          0.030000   1.000  1.000

27002221 D    Milk, fat - baby food/infant for   0.030000   1.000  1.000

27012230 D    Milk, nonfat solids                0.030000   1.000  1.000

27012231 D    Milk, nonfat solids-baby food/in   0.030000   1.000  1.000

27022240 D    Milk, water                        0.030000   1.000  1.000

27022241 D    Milk, water-babyfood/infant form   0.030000   1.000  1.000

27032251 D    Milk, sugar (lactose)-baby food/   0.030000   1.000  1.000

05022290 5B   Mustard greens                    16.000000   1.000  1.000

12002300 12   Nectarine                          0.600000   1.000  1.000

08002340 8    Okra                               0.400000   1.000  1.000

04012480 4A   Parsley, leaves                    4.000000   1.000  1.000

01012500 1AB  Parsley, turnip rooted             0.600000   1.000  1.000

01012510 1AB  Parsnip                            0.600000   1.000  1.000

01012511 1AB  Parsnip-babyfood                   0.600000   1.000  1.000

12002600 12   Peach                              0.600000   1.000  1.000

12002601 12   Peach-babyfood                     0.600000   1.000  1.000

12002610 12   Peach, dried                       0.600000   7.000  1.000

12002611 12   Peach, dried-babyfood              0.600000   7.000  1.000

12002620 12   Peach, juice                       0.600000   1.000  1.000

12002621 12   Peach, juice-babyfood              0.600000   1.000  1.000

11002660 11   Pear                               0.200000   1.000  1.000

11002661 11   Pear-babyfood                      0.200000   1.000  1.000

11002670 11   Pear, dried                        0.200000   6.250  1.000

11002680 11   Pear, juice                        0.200000   1.000  1.000

11002681 11   Pear, juice-babyfood               0.200000   1.000  1.000

08002700 8    Pepper, bell                       0.400000   1.000  1.000

08002701 8    Pepper, bell-babyfood              0.400000   1.000  1.000

08002710 8    Pepper, bell, dried                0.400000   1.000  1.000

08002711 8    Pepper, bell, dried-babyfood       0.400000   1.000  1.000

08002720 8    Pepper, nonbell                    0.400000   1.000  1.000

08002721 8    Pepper, nonbell-babyfood           0.400000   1.000  1.000

08002730 8    Pepper, nonbell, dried             0.400000   1.000  1.000

12002850 12   Plum                               0.600000   1.000  1.000

12002851 12   Plum-babyfood                      0.600000   1.000  1.000

12002860 12   Plum, prune, fresh                 0.600000   1.000  1.000

12002861 12   Plum, prune, fresh-babyfood        0.600000   1.000  1.000

12002870 12   Plum, prune, dried                 0.600000   5.000  1.000

12002871 12   Plum, prune, dried-babyfood        0.600000   5.000  1.000

12002880 12   Plum, prune, juice                 0.600000   1.400  1.000

12002881 12   Plum, prune, juice-babyfood        0.600000   1.400  1.000

01032960 1C   Potato, chips                      0.200000   1.000  1.000

01032970 1C   Potato, dry (granules/ flakes)     0.400000   1.000  1.000

01032971 1C   Potato, dry (granules/ flakes)-b   0.400000   1.000  1.000

01032980 1C   Potato, flour                      0.200000   6.500  1.000

01032981 1C   Potato, flour-babyfood             0.200000   6.500  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               0.030000   1.000  1.000

60003020 P    Poultry, other, liver              0.030000   1.000  1.000

60003030 P    Poultry, other, meat byproducts    0.030000   1.000  1.000

60003040 P    Poultry, other, fat                0.030000   1.000  1.000

60003050 P    Poultry, other, skin               0.030000   1.000  1.000

09023080 9B   Pumpkin                            0.400000   1.000  1.000

09023090 9B   Pumpkin, seed                      0.400000   1.000  1.000

11003100 11   Quince                             0.200000   1.000  1.000

04013130 4A   Radicchio                          4.000000   1.000  1.000

01013140 1AB  Radish, roots                      0.600000   1.000  1.000

02003150 2    Radish, tops                      16.000000   1.000  1.000

01013160 1AB  Radish, Oriental, roots            0.600000   1.000  1.000

05023180 5B   Rape greens                       16.000000   1.000  1.000

04023220 4B   Rhubarb                            4.000000   1.000  1.000

01013270 1AB  Rutabaga                           0.600000   1.000  1.000

01013310 1AB  Salsify, roots                     0.600000   1.000  1.000

26003390 M    Sheep, meat                        0.080000   1.000  1.000

26003391 M    Sheep, meat-babyfood               0.080000   1.000  1.000

26003400 M    Sheep, meat byproducts             0.080000   1.000  1.000

26003410 M    Sheep, fat                         0.030000   1.000  1.000

26003411 M    Sheep, fat-babyfood                0.030000   1.000  1.000

26003420 M    Sheep, kidney                      0.080000   1.000  1.000

26003430 M    Sheep, liver                       0.080000   1.000  1.000

04013550 4A   Spinach                            9.000000   1.000  1.000

04013551 4A   Spinach-babyfood                   9.000000   1.000  1.000

09023560 9B   Squash, summer                     0.400000   1.000  1.000

09023561 9B   Squash, summer-babyfood            0.400000   1.000  1.000

09023570 9B   Squash, winter                     0.400000   1.000  1.000

09023571 9B   Squash, winter-babyfood            0.400000   1.000  1.000

01033660 1CD  Sweet potato                       0.200000   1.000  1.000

01033661 1CD  Sweet potato-babyfood              0.200000   1.000  1.000

04023670 4B   Swiss chard                        4.000000   1.000  1.000

01033710 1CD  Tanier, corm                       0.200000   1.000  1.000

08003740 8    Tomatillo                          0.400000   1.000  1.000

08003750 8    Tomato                             0.400000   1.000  1.000

08003751 8    Tomato-babyfood                    0.400000   1.000  1.000

08003760 8    Tomato, paste                      2.000000   1.000  1.000

08003761 8    Tomato, paste-babyfood             2.000000   1.000  1.000

08003770 8    Tomato, puree                      0.500000   1.000  1.000

08003771 8    Tomato, puree-babyfood             0.500000   1.000  1.000

08003780 8    Tomato, dried                      0.400000  14.300  1.000

08003781 8    Tomato, dried-babyfood             0.400000  14.300  1.000

08003790 8    Tomato, juice                      0.400000   1.500  1.000

50003820 P    Turkey, meat                       0.030000   1.000  1.000

50003821 P    Turkey, meat-babyfood              0.030000   1.000  1.000

50003830 P    Turkey, liver                      0.030000   1.000  1.000

50003831 P    Turkey, liver-babyfood             0.030000   1.000  1.000

50003840 P    Turkey, meat byproducts            0.030000   1.000  1.000

50003841 P    Turkey, meat byproducts-babyfood   0.030000   1.000  1.000

50003850 P    Turkey, fat                        0.030000   1.000  1.000

50003851 P    Turkey, fat-babyfood               0.030000   1.000  1.000

50003860 P    Turkey, skin                       0.030000   1.000  1.000

50003861 P    Turkey, skin-babyfood              0.030000   1.000  1.000

01033870 1CD  Turmeric                           0.200000   1.000  1.000

05023890 5B   Turnip, greens                    16.000000   1.000  1.000

01013880 1AB  Turnip, roots                      0.600000   1.000  1.000

86010000 O    Water, direct, all sources

                 110-Uncooked; Fresh or N/S; Cook Meth N/S

                                                 0.001500   1.000  1.000

86020000 O    Water, indirect, all sources       0.001500   1.000  1.000

09013990 9A   Watermelon                         0.400000   1.000  1.000

09014000 9A   Watermelon, juice                  0.400000   1.000  1.000

01034060 1CD  Yam, true                          0.200000   1.000  1.000

01034070 1CD  Yam bean                           0.200000   1.000  1.000

Attachment 2:  DEEM(-FCID Chronic Results

U.S. Environmental Protection Agency                                 Ver. 2.00

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

Residue file name: C:\Documents and Settings\aacierto\Desktop\Flonicamid.DEEMr\FLONICAMID.R98

                                                 Adjustment factor #2 NOT used.

Analysis Date 11-16-2007/14:18:07     Residue file dated: 11-16-2007/14:10:38/8

Reference dose (RfD, Chronic) = .04 mg/kg bw/day

NOEL (Chronic) = 4 mg/kg bw/day

COMMENT 1: CHRONIC ONLY

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

                    Total exposure by population subgroup

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

                                                    Total Exposure

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

          Population                         mg/kg       Margin of   Percent

           Subgroup                       body wt/day   Exposure 1/  of RfD

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

U.S. Population (total)                     0.004095          977       10.2%

U.S. Population (spring season)             0.004096          976       10.2%

U.S. Population (summer season)             0.004141          966       10.4%

U.S. Population (autumn season)             0.004133          968       10.3%

U.S. Population (winter season)             0.004001        1,000       10.0%

Northeast region                            0.004258          939       10.6%

Midwest region                              0.003893        1,028        9.7%

Southern region                             0.003940        1,015        9.8%

Western region                              0.004410          907       11.0%

Hispanics                                   0.003861        1,036        9.7%

Non-hispanic whites                         0.003770        1,061        9.4%

Non-hispanic blacks                         0.005283          757       13.2%

Non-hisp/non-white/non-black                0.006604          606       16.5%

All infants (< 1 year)                      0.006087          657       15.2%

Nursing infants                             0.003118        1,283        7.8%

Non-nursing infants                         0.007214          554       18.0%

Children 1-6  yrs                           0.007597          527       19.0%

Children 7-12 yrs                           0.004241          943       10.6%

Females 13-19 (not preg or nursing)         0.003055        1,309        7.6%

Females 20+ (not preg or nursing)           0.003819        1,047        9.5%

Females 13-50 yrs                           0.003587        1,115        9.0%

Females 13+ (preg/not nursing)              0.003024        1,323        7.6%

Females 13+ (nursing)                       0.003991        1,002       10.0%

Males 13-19 yrs                             0.003486        1,148        8.7%

Males 20+ yrs                               0.003546        1,128        8.9%

Seniors 55+                                 0.004002          999       10.0%

Children 1-2 yrs                            0.009070          441       22.7%

Children 3-5 yrs                            0.007205          555       18.0%

Children ⴶ㈱礠獲†††††††††††††〠〮㐰㠴″†† ††㠠㈹†††ㄠ⸱┲复畯桴ㄠⴳ㤱礠獲†††††† ††††††††〠〮㌰㠲‰†††ㄠ㈬㤱††††⸸ ┲䄍畤瑬⁳〲㐭‹特⁳†††††††††††††〠 〮㌰ㄵ″†††ㄠㄬ㤳††††⸸┸

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Adults 50+ yrs                              0.003978        1,005        9.9%

Females 13-49 yrs                           0.003504        1,142        8.8%

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

Flonicamid				Dietary Exposure Assessment		DP Barcode: D343466

PC Code:

Page( PAGE  1 (of(( NUMPAGES  17


1 Summary of Summary of EPA Ethics Review EPA Ethics Review MRID 44400401 Russell, M., Rush, T. ( 1996) Methyl Isothiocyanate: Determination of Human Olfactory Threshold and Human No Observable Effect Level for Eye Irritation. Unpublished study performed by Sensory Testing Laboratory, School of Medicine, Univ. of California, Davis, and Zeneca Ag Products Western Research Center, Richmond CA. Project numbers MITCUCD 1A 1993 and MITC UCD 1B 1994; Report no. RR 96 049B.

136 p. Supplemented by MRIDs 46546601, 46558201, and 46584901 2 MITC Study Summary MITC Study Summary

Two entirely independent studies covered by a single report

Odor threshold study conducted at UC Davis in 1992 93

Eye irritation study conducted at UC Davis in 1994 95

The studies differ sharply in their ethical conduct, and are reviewed separately 3 MITC Odor Study MITC Odor Study " Framework Framework"

1. Value  Not published or disseminated  Societal value not addressed in reports 2. Scientific Validity: Defer to others 3. Subject Selection  38 adult male and female volunteers from university community  Recruitment methods not reported; no evidence of use of vulnerable groups 4 MITC Odor Study MITC Odor Study " Framework Framework"

 2 4. Risk Benefit Ratio  Risks characterized to IRB first as " no risk", and later as " minimal risk"

 Risk minimization not discussed  No record of how risks were characterized to subjects  Societal or other benefits not addressed  Weighing of societal benefits against risks to subjects not addressed 5 MITC Odor Study MITC Odor Study " Framework Framework"

 3 5. Independent Ethics Review  Approved by UC Davis Human Subjects Review Committee, initially in 1989 and annually thereafter  Initial approval was for " scratch and sniff" mail out survey  MITC was first use of " olfactometer"

 No documentation of IRB approval for period of MITC study  No documentation of protocol or informed consent materials for MITC study  IRB failed to respond to investigator's request for waiver of written informed consent until 3 years after MITC work was completed 6 MITC Odor Study MITC Odor Study " Framework Framework"

 4 6. Informed Consent  Primary report silent about consent  Supplement asserts oral information and oral consent, through note to file of telephone call  No documentation of IRB waiver of Common Rule requirement for written consent  No documentation of what subjects were told 7 MITC Odor Study MITC Odor Study " Framework Framework"

 5 7. Respect for Subjects  Subject privacy was protected  Subject freedom to withdraw was not addressed 8 MITC Odor Study: Prevailing Standards MITC Odor Study: Prevailing Standards

Conducted in US in 1992 3 at UC Davis

Cites and asserts compliance with Declaration of Helsinki

UC Davis held federal Multi Project Assurance at time of research, promising full compliance with Common Rule 9 Comparison to Comparison to DoH DoH

Basic Principle # 2: ". . . Each experimental procedure . . should be clearly formulated in an experimental protocol, which should be transmitted . . to a specially appointed committee . . ."

EPA Comment: Protocol was not clearly formulated. MITC work was unrelated to mail survey work described in protocol reviewed and approved by IRB 10 Comparison to Comparison to DoH DoH

 2

Basic Principle # 5: " Every . . . project . . .

should be preceded by careful assessment of predictable risks in comparison with foreseeable benefits to the subject or to others."

EPA Comment: If a careful assessment was conducted it was not reported 11 Comparison to Comparison to DoH DoH   3a 3a

Basic Principle # 9: " each potential subject must be adequately informed of the aims,

methods, anticipated benefits and potential hazards of the study and the discomfort it may entail. . . [ and] should be informed that . . . he or she is free to withdraw. . . at any time. The [ investigator] should then obtain the subject's freely given informed consent, preferably in writing." 12 Comparison to Comparison to DoH DoH   3b 3b

EPA Comment: The primary report was silent about consent. The information provided to the IRB was irrelevant to the work with MITC.

There is no documentation of the context,

procedure, or content of the asserted oral consent process. 13 Comparison to Comparison to DoH DoH

 4

Basic Principle # 12: " The research protocol should always contain a statement of the ethical considerations involved . . . ."

EPA Comment: There is no such statement in the protocol 14 Comparison to Common Rule Comparison to Common Rule

§ 111( a)( 2): [ to approve research . . . The IRB shall determine that] " risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may be reasonably expected to result."

EPA Comment: IRB records indicate no discussion of either risks or benefits 15 Comparison to Common Rule Comparison to Common Rule

 2

§ 111( a)( 4): [ to approve research . . . The IRB shall determine that] " informed consent will be sought from each prospective subject.

. ."

EPA Comment: IRB records do not reflect any discussion of informed consent 16 Comparison to Common Rule Comparison to Common Rule

 3

§ 111( a)( 5): [ to approve research . . . The IRB shall determine that] " Informed consent will be appropriately documented, in accordance with, and to the extent required by Sec. 26.117"

EPA Comment: IRB records do not indicate the board noticed or discussed the investigator's request for waiver of written consent 17 Comparison to Common Rule Comparison to Common Rule

 4

§ 115: IRB Records

EPA Comment: IRB records fall well short of the requirements of the CR

§ 116: General Requirements for Informed Consent

EPA Comment: Compliance of undocumented oral consent process with these requirements cannot be assessed 18 Comparison to Common Rule Comparison to Common Rule

 5

§ 117: Documentation of Informed Consent

EPA Comment: The failure to document consent or to waive the requirement falls short of Common Rule standards 19 MITC Odor Study Summary MITC Odor Study Summary

Gaps in the record, but gaps are not " clear and convincing evidence"

No evidence that the research was fundamentally unethical

No evidence that subjects included children or pregnant women

Many clear deficiencies relative to the cited Declaration of Helsinki and the Common Rule

We welcome the Board's advice on the significance of those deficiencies 20 MITC Eye Study MITC Eye Study " Framework Framework"

1. Value  Not published or disseminated  Societal value not addressed in reports 2. Scientific Validity: Defer to others 3. Subject Selection  Adult male and female volunteers from university community; number unclear  Recruitment methods suggest some subjects may have been students or colleagues of investigators 21 MITC Eye Study MITC Eye Study " Framework Framework"

 2 4. Risk Benefit Ratio  Risks characterized to subjects as " transient irritation and tearing"

 Risk minimization not discussed  Societal or other benefits not addressed  Weighing of societal benefits against risks to subjects not addressed  Subjects compensated $ 60 250 depending on duration of study phase 22 MITC Eye Study MITC Eye Study " Framework Framework"

 3 5. Independent Ethics Review  Initial approval by UC Davis Human Subjects Review Committee and annual renewals with protocol revisions are documented  IRB discussion not documented 23 MITC Eye Study MITC Eye Study " Framework Framework"

 4 6. Informed Consent  Consent materials are brief, but clear  Consent materials include all elements required by Common Rule § 116 7. Respect for Subjects  Subject privacy was protected  Subjects were free to withdraw 24 MITC Eye Study: Prevailing Standards MITC Eye Study: Prevailing Standards

Conducted in US in 1994 5 at UC Davis

Cites and asserts compliance with Declaration of Helsinki

UC Davis held federal Multi Project Assurance at time of research, promising full compliance with Common Rule 25 Comparison to Prevailing Standards Comparison to Prevailing Standards

Documentation of risk reduction is weak

Documentation of societal benefit is weak

Possibility of undue influence in recruiting students of investigator

General compliance with Declaration of Helsinki and Common Rule 26 MITC Eye Study Summary MITC Eye Study Summary

Minor gaps in the record, but gaps are not " clear and convincing evidence"

No children; no pregnant females; no evidence that the research was fundamentally unethical

No noteworthy deficiencies relative to the cited Declaration of Helsinki or the Common Rule


[Federal Register Volume 78, Number 159 (Friday, August 16, 2013)]
[Proposed Rules]
[Page 49990]
[FR Doc No: 2013-19915]

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

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 172

[Docket No. FDA-2013-N-0888]

Dean Foods Company and WhiteWave Foods Company; Filing of Food
Additive Petition

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of petition.

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

SUMMARY: The Food and Drug Administration (FDA or we) is announcing
that we have filed a petition submitted by the Dean Foods Company and
the WhiteWave Foods Company proposing that the food additive
regulations be amended to provide for the expanded safe uses of vitamin
D2 and vitamin D3 as nutrient supplements in
food.

DATES: The food additive petition was filed on June 27, 2013.

FOR FURTHER INFORMATION CONTACT: Judith Kidwell, Center for Food Safety
and Applied Nutrition (HFS-265), Food and Drug Administration, 5100
Paint Branch Pkwy., College Park, MD 20740-3835,<PHONE_NUMBER>.

SUPPLEMENTARY INFORMATION: Under section 409(b)(5) of the Federal Food,
Drug, and Cosmetic Act (21 U.S.C. 348(b)(5)), we are giving notice that
we have filed a food additive petition (FAP 3A4801), submitted by the
Dean Foods Company and the WhiteWave Foods Company, c/o Hogan Lovells
US LLP, Columbia Square, 555 Thirteenth Street NW., Washington, DC
20004. The petition proposes to amend 21 CFR 172.379 to provide for the
safe use of vitamin D2 as a nutrient supplement in edible
plant-based food products intended for use as alternatives to milk and
milk products and to amend 21 CFR 172.380 to provide for the safe use
of vitamin D3 as a nutrient supplement in milk at levels
higher than those currently permitted.
    We have determined under 21 CFR 25.32(k) that this action is of a
type that does not individually or cumulatively have a significant
effect on the human environment. Therefore, neither an environmental
assessment nor an environmental impact statement is required.

    Dated: August 12, 2013.
Dennis M. Keefe,
Director, Office of Food Additive Safety, Center for Food Safety and
Applied Nutrition.
[FR Doc. 2013-19915 Filed 8-15-13; 8:45 am]
BILLING CODE 4160-01-P