Dietary Exposure and Risk Assessment

Kasugamycin PC Code 230001 DP Barcode D 3 904 58

Page 3 of 9 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

a re available on the EPA pesticides web site, Available Information on Assessing Exposure from

Pesticides

, A User’s Guide ( 21 June 2000 )

, which can be accessed via the web link http://www.epa.gov/fedrgstr/EPA

- PEST/2000/July/Day

- 12/6061.pdf ( or see SOP 99.6 , dated 20 August 19 99).

The most recent dietary risk assessment for kasugamycin was conducted by W.T. Drew ( D 358667 ; 16 January 2009 ). That assessment support ed the Section 18 tolerances for residues

of kasugamycin arising fr om its use on apples in Michigan

. This current docu ment includes

residue estimates for kasugamycin in or on fruiting vegetable , pome fruit, and walnut

commoditie s , support ing the requested Section 3 registration of kasugamycin for use in the US

.

2

. Residue Information

This dietary assessment i nclude s residue estimates supporting the requested Section 3 registration of kasugamycin for use on fruiting vegetables (crop group 8

- 10 ) , pome fruit s (crop group 11

- 10 ) , and walnuts . The residue of concern

, for both tolerance enforcement and risk

assessment

, is the parent compound, kasugamycin

. R esidues resulting from use of kasugamycin

are assumed to be at the tolerance level s recommended by HED (0.15 ppm in fruiting vegetable s, 0. 30 ppm in pears, 0.0 8 ppm in all pome fruit other than pears, and 0.0 7 ppm in walnuts)

.

Default processing factors from DEEM 7.8 1 we re used in the analys i s except for apple juice, for which the empirical factor from the processing study (1.5 X ) was used

.

A complete listing of the residues and processing factors used in the chronic dietary analysis is

included in Att achment 1.

Tolerances have been established for kasugamycin (40CFR §180.614) in / on imported fruiting vegetable s (crop group 8) at 0.04 ppm. A time

- limited ( Section 18) tolerance ha s also been

established at 0.0 5 ppm for kasugamycin in/ on apples grown in Michigan

. These tolerances will be superseded by those listed above when the proposed new uses are registered.

3. Percent Crop Treated Information

The chronic assessment is highly conservative

, and assumes that all crops with existing or

currentl y requested uses bear residues of kasugamycin (in other words, 100%CT).Dietary Exposure and Risk Assessment

Kasugamycin PC Code 230001 DP Barcode D 3 904 58

Page 4 of 9 4

. Drinking Water Data

The drinking water residues used in th i s dietary risk assessment were provided by EFED ( D376600 ; T. Dowen ; 28 April 2011 )

, and incorporated directly into th e dietary assessment via

entry into the food categories “water, direct, all sources” and “water, indirect, all sources.” The

EDWCs in surface water are 0.0 1156 2 ppm and 0.001178 ppm for acute and chronic scenarios, respectively. The EDWC in groundwater is 0. 000 116 ppm for all durations (see Table 1, below)

. T h e chronic surface water EDWC ( 0.001178 ppm ) was used in the chronic dietary analysis because it is the higher of the chronic residues in water

.

The surface water EDWC s w ere obtained via exposure modeling which utilized the PRZM (Pesticide Root Zone Model) and EXAMS (E X posure Analysis Modeling System) model s

. Th e s e model s and t heir description s are available at the EPA internet web site via the web link

, http://www.epa.gov/oppefed1/models/water/

. The PRZM/ EXAMS m odeling was based on application of kasugamycin to tomato es in Florida

.

TABLE 1 EDWCs for Kasugamycin, Plus Degradates Kasugamycinic Acid and Kasuganobiosamine.

Crop Acute Exposure (ppm) Chronic Exposure (ppm) Cancer Exposure ( ppm )

Surface Water ( via PRZM/EXAMS)

Tomato 0.0 11562 0.00 1178 * 0.00 0602

Ground Water ( via SCI

- GROW)

Walnut 0. 000 116 0. 000 116 0. 000 116

* EDWC used in the chronic dietary assessment.

5

. DEEM

- FCIDTM Program and Consumption Information

The kasugamycin chronic dietary exposure asses sment w as conducted using DEEM

- FCIDTM ( Version 2.03), which incorporates consumption data from USDA’s CSFII, 1994 to 1996

, and

1998. The 1994

- 96, 19 98 data are based on the reported consumption of more than 20,000

individuals over two non

- consecutive survey days. Foods “as consumed” ( such as apple pie) are

linked to EPA

- defined food commodities ( such as apples, peeled fruit

- cooked, fresh/unspecified, or baked; or wheat flour

- cooked, fresh/unspecified, or baked ) using publicly available recipe tran slation files developed jointly by USDA/ARS and EPA. For chronic exposure assessment, consumption data are averaged for the entire US population

, and within population subgroups, but for acute exposure assessment

, they are retained as individual consumption events. Based on analysis of the 1994

- 96, 19 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 popul ation subgroups: the general US population, allDietary Exposure and Risk Assessment

Kasugamycin PC Code 230001 DP Barcode D 3 904 58

Page 5 of 9 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 lev el in each food or food

form ( such as orange or orange juice) on the food commodity residue list is multiplied by the average daily consumption estimate for that food/food form. The resulting residue consumption

estimate for each food/food form is summed with the residue consumption 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 performe d for each population subgroup.

For acute exposure assessments, individual one

- day food consumption data are used on an

individual

- by

- individual basis. The reported consumption amounts of each food item can be multiplied by a residue point estimate

, an d summed to obtain a total daily pesticide exposure for a deterministic exposure assessment, or “matched” in multiple random pairings with residue

values

, and then summed in a probabilistic assessment. The resulting distribution of exposures is expressed as a percentage of the aPAD on both a user (those who reported eating relevant commodities/food forms) and a per

- capita (those who reported eating the relevant commodities as well as those who did not) basis. In accordance with HED policy, per capita expo sure and risk are reported for all dietary analys e s , regardless of the degree of refinement (unrefined through highly refined) . However, for unrefined or slightly refined analyses , significant differences in

user v ersu s per capita exposure and risk are id entified

, and noted in the risk assessment.

6

. Toxicological Information

For detailed information, please refer to the human health risk assessment conducted for kasugamycin’s use on fruiting vegetables, pome fruit, and walnuts ( D 3 766 0 8 ; W.T. Drew ; 13 July 2012 ). T he available database is considered of high quality, and is adequate for assessment

of risk for th e proposed use s

.

The chronic reference dose (cRfD) is 0.1 1 mg/kg/day. The NOAEL of 1 1 mg/kg/day is from the

rat chronic toxicity/carcinogenicity study . This NOAEL was selected for the cRfD because it was of the appropriate route and duration, and is protective of effects seen in other studies. Although the testicular findings were not statistically significant com pared to controls, these effects were selected as the basis for the study LOAEL because the incidence and severity were increased, and similar degenerative testicular effects were seen across species. The selected endpoint is also protective of maternal a nd developmental toxicity (weight loss

, decreased food consumption during dosing, abortion in one female, and decreased fetal weight) that was seen in the rabbit developmental toxicity range

- finding study. No developmental toxicity was seen in

the rat

, an d maternal toxicity was seen at 1000 mg/kg/day (200 mg/kg/day).Dietary Exposure and Risk Assessment

Kasugamycin PC Code 230001 DP Barcode D 3 904 58

Page 6 of 9 The risk assessment team has confirmed that the selected doses and endpoints are appropriate to

assess the currently proposed use s on fruiting vegetables, pome fruit, and walnuts

. T h es e doses and endpoints are summarized in Table 2 , below.

TABLE 2 Summary of Kasugamycin Toxicological Doses and Endpoints for Use in Dietary Human

Health Risk Assessments. Exposure Scenario Point of

Departure Uncertainty

and FQPA Safety Factors RfD, PAD for Risk

Assessment Study and Toxicological Effects

Acute dietary (all populations) Not required. Appropriate endpoints for this risk assessment scenario were not identified

,

based on a lack of single

- dose effects in the database

. Chronic dietary (all populations

, including infants and

children

, and females age 13 to 49 ) NOAEL = 11

mg/kg/day UF A = 10X

UF H = 10X FQPA SF= 1 X Chronic RfD = 0.1 1

mg/kg/day

cPAD = 0.1 1 mg/kg/day Combined chronic

toxicity/carcinogenicity study in

the rat

. LOAEL = 116 mg/kg/day, based on testicular atrophy and softening

. Cancer (oral, dermal, inhalation) Classification: “ N ot likely to be carcinogenic to humans

. ” No oncogenic potential was

noted in either the mouse oncogenicity or in the rat combined chronic/carcinogenicity studies. Additionally, no mutagenic potential was noted in any of the mutagenicity studies.
Point of Departure (POD) = a data point or estimated point derived from observed dose

- response data

, which is used to mark the beginning of extrapolation to determine risk associa ted with lower environmentally relevant human

exposures. UF = Uncertainty Factor. UF A = extrapolation from animal to human (interspecies). UF H = potential variation in sensitivity among mem bers of the human population (intraspecies). FQPA SF = FQPA Safety Factor.

NOAEL = No Observed Adverse Effect Level. LOAEL = Lowest Observed Adverse Effect Level. PAD = Population Adjusted Dose (a = acute, c = chronic). RfD = Reference Dose.

7

. Results/Discussion

As previously stated , for chronic assessments, HED is concerned when dietary risk exceeds

100% of the c PAD. The DEEM

- FCIDTM analyses estimate the dietary exposure of the US population

, and the various population subgroups.

The result s of the chronic analys i s are summarized in Table 3 , below . The exposure estimates

are considered very conservative because tolerance

- level residues, and 100% CT w ere assumed

. As indicated in Table 3 , the chronic risk estimates are not of concern for a ny of the population subgroups.

Children 1

- 2 year s of age are the most highl y

- exposed subgroup, utilizing 1 .7 % of the cPAD, while the general US population utilizes <1 % of the cPAD.Dietary Exposure and Risk Assessment

Kasugamycin PC Code 230001 DP Barcode D 3 904 58

Page 7 of 9 TABLE 3 Summary of Chronic Dietary Exposure and Risk Estimates for Kas ugamycin

. Population Subgroup* [Years of Age] cPAD (mg/kg/day) Dietary Exposure Estimate (mg/kg/day) % cPAD

General US Population 0.1 1 0.000450 <1

All Infants [< 1] 0.1 1 0.001215 1. 1

Children [1

- 2] 0.1 1 0.001839 1. 7

Children [3

- 5] 0.1 1 0.001281 1. 2

Children [6

- 12] 0.1 1 0.000647 <1

Youth [13

- 19] 0.1 1 0.000373 <1

Adults [20

- 49] 0.1 1 0.00031 0 <1

Adults [50+] 0.1 1 0.000279 <1

Females [13

- 49] 0.1 1 0.000307 <1

* Values for the population subgroup with the highest risk are in bold type

.

8

. Characterization of Inputs/Outputs

This assessment is based on tolerance

- level residue s , and assumes that all crops with either current or proposed kasugamycin tolerances are treated (100%CT) . These assumptions result in highly conservative, health

- prote ctive estimates of dietary exposure and risk.

9

. Conclusions

A n unrefined chronic dietary assessment was conducted for a ll current and proposed uses of kasugamycin

. There are no dietary exposure considerations that woul d preclude the

establishment of tolerance s for residues of kasugamycin in/on fruiting vegetables, pome fruit,

and walnuts

. Children 1

- 2 year s of age are the most highl y

- exposed subgroup, utilizing 1.7 % of the cPAD, while the general US population utilizes <1 % of the cPAD.

10

. List of Attachments

Attachment 1. Kasugamycin Residues Used for Chronic Dietary Exposure Estimates.

Attachment 2. Summary of the Chronic Dietary Exposure and Risk Estimates for Kasugamycin

.Dietary Exposure and Risk Assessment

Kasugamycin PC Code 230001 DP Barcode D 3 904 58

Page 8 of 9 Attachment 1. Kasugamycin Residues Used for Chronic Dietary Exposure Estimates.

US Environmental Protection Agency

DEEM

- FCID Ver sion 2.03 (1994

- 1996, 19 98 data)

Filename: KasugamycinDEEM0 6 0 5 1 2 Input.R98

Chemical: Kasugamycin

Chronic r eference dose (RfD, Chronic) : 0 .1 1 mg/kg b ody w eight /day

Date created or last modified: 6 / 5 / 201 2 at 1 0 02

EPA Crop Def Res Adj.Factors Comment
Code Grp Commodity Name (ppm) #1 #2

11000070 11 Apple, fruit with peel 0.080000 1.000 1.000 0F7689 11000080 11 Apple, peeled fruit 0.080000 1.000 1.000 0F7689 11000081 11 Apple, peeled fruit

- babyfood 0.080000 1.000 1.000 0F7689 11000090 11 Apple, dried 0.080000 8.000 1.000 0F7689 11000091 11 Apple, dried

- babyfood 0.080000 8.000 1.000 0F7689 11000100 11 Apple, juice 0.080000 1.500 1.000 0F76 89 11000101 11 Apple, juice

- babyfood 0.080000 1.500 1.000 0F7689 11000110 11 Apple, sauce 0.080000 1.000 1.000 0F7689 11000111 11 Apple, sauce

- babyfood 0.080000 1.000 1.000 0F7689

11001290 1 1 Crabapple 0.080000 1.000 1.000 0F7689 08001480 8 Eggplant 0.150000 1.000 1.000 0F7689 11002100 11 Loquat 0.080000 1.000 1.000 0F7689

08002340 8 Okra 0.150000 1.000 1.000 0F7689

11002660 11 Pear 0.300000 1.000 1.000 0F7689

11002661 11 Pear

- babyfood 0.300000 1.000 1.000 0F7689
11002670 11 Pear, dried 0.300000 6.250 1.000 0F7689 11002680 11 Pear, juice 0.300000 1.000 1.000 0F7689 11002681 11 Pear, juice

- babyfood 0.300000 1.000 1.000 0F7689 08002700 8 Pepper, bell 0.150000 1.000 1.000 0F7689 08002701 8 Pepper, bell

- babyfood 0.150000 1.000 1.000 0F7689 08002710 8 Pepper, bell, dried 0.150000 1.000 1.000 0F7689

08002711 8 Pepper, bell, dried

- babyfood 0.150000 1.000 1.000 0F7689 08002720 8 Pepper, nonbell 0.150000 1.000 1.000 0F7689 08002721 8 Pepper, nonbell

- babyfood 0.150000 1.000 1.000 0F7689 08002730 8 Pepper, nonb ell, dried 0.150000 1.000 1.000 0F7689
11003100 11 Quince 0.080000 1.000 1.000 0F7689

08003740 8 Tomatillo 0.150000 1.000 1.000 0F7689

08003750 8 Tomato 0.150000 1.000 1.000 0F7689

08003751 8 Tomato

- babyfood 0.150000 1.000 1.000 0F7689 08003760 8 Tomato, paste 0.150000 5.400 1.000 0F7689 08003761 8 Tomato, paste

- babyfood 0.1 50000 5.400 1.000 0F7689 08003770 8 Tomato, puree 0.150000 3.300 1.000 0F7689 08003771 8 Tomato, puree

- babyfood 0.150000 3.300 1.000 0F7689
08003780 8 Tomato, dried 0.150000 14.300 1.000 0F7689
08003781 8 Tomato, dried

- babyfood 0.150000 14.300 1.000 0F7689 08003790 8 Tomato, juice 0.150000 1.500 1.000 0F7689
95003800 O Tomato, Tree 0.150000 1.000 1.000 0F76 89

14003910 14 Walnut 0.070000 1.000 1.000 0F7689
86010000 O Water, direct, all sources 0.001178 1.000 1.000 0F7689
86020000 O Water, indirect, all sources 0.001178 1.000 1.000 0F768 9Dietary Exposure and Risk Assessment

Kasugamycin PC Code 230001 DP Barcode D 3 904 58

Page 9 of 9 Attachment 2. Summary of the Chronic Dietary Exposure and Risk Estimates for

Kasugamycin

.

US Environmental Protection Agency

DEEM

- FCID Ver sion 2.03 (1994

- 1996, 19 98 data)

, Chronic analysis for K ASUGAMYCIN

Residue file name: KasugamycinDEEM0 6 0 5 1 2 Input.R98 Adjustment factor #2 was NOT used. Analysis d ate : 6 / 5/ 201 2 at 10 07

Residue file date : 6 /5 / 201 2 at 10 0 2

Chronic r eference dose (RfD, Chronic) = 0 .1 1 mg/kg b ody w eight /day

Total Exposure by Population S ubgroup

Total Exposure

----------------------------------- Population mg/kg Percent of
Subgroup bo dy wt/day cPAD

U.S. Population (total) 0.000450 0.4%

U.S. Population (spring season) 0.000437 0.4% U.S. Population (summer season) 0.000434 0. 4% U.S. Population (autumn season) 0.000466 0.4% U.S. Population (winter season) 0.000465 0.4%

Northeast region 0.000484 0.4% Midwest region 0.000452 0.4% Southern region 0.000412 0.4% Western region 0.000479 0.4%

Hispanics 0.000541 0.5%

Non

- hispanic whites 0.000437 0.4%

Non

- hispanic blacks 0.000436 0.4%

Non

- hisp/non

- white/non

- black 0.000489 0.4%

All infants (< 1 year) 0.001215 1.1% Nursing infants 0.000653 0.6%

Non

- nursing infants 0.001428 1.3%

Children 1

- 6 yrs 0.001412 1.3%

Children 7

- 12 yrs 0.000593 0.5%

Females 13

- 19 (not preg or nursing) 0.000379 0.3% Females 20+ (not preg or nursing) 0.000284 0.3%

Females 13

- 50 y rs 0.000346 0.3% Females 13+ (preg/not nursing) 0.000399 0.4%
Females 13+ (nursing) 0.000342 0.3%

Males 13

- 19 yrs 0.00 0368 0.3% Males 20+ yrs 0.000312 0.3%

Seniors 55+ 0.000279 0.3%

Children 1

- 2 yrs 0.001839 1.7%

Childre n 3

- 5 yrs 0.001281 1.2%

Children 6

- 12 yrs 0.000647 0.6%

Youth 13

- 19 yrs 0.000373 0.3%

Adults 20

- 49 yrs 0.000310 0.3% Adults 50+ yrs 0.000279 0.3%

Females 13

- 49 yrs 0.000307 0.3%