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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 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 1999). 

The most recent dietary risk assessment for kasugamycin was conducted by W.T. Drew

(D358667; 16 January 2009). That assessment supported the Section 18 tolerances for residues

of kasugamycin arising from its use on apples in Michigan. This current document includes 

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

commodities, supporting the requested Section 3 registration of kasugamycin for use in the US. 

2. Residue Information

This dietary assessment includes residue estimates supporting the requested Section 3

registration of kasugamycin for use on fruiting vegetables (crop group 8-10), pome fruits (crop 

group 11-10), and walnuts. The residue of concern, for both tolerance enforcement and risk 

assessment, is the parent compound, kasugamycin. Residues resulting from use of kasugamycin

are assumed to be at the tolerance levels recommended by HED (0.15 ppm in fruiting vegetables, 

0.30 ppm in pears, 0.08 ppm in all pome fruit other than pears, and 0.07 ppm in walnuts). 

Default processing factors from DEEM 7.81 were used in the analysis except for apple juice, for 

which the empirical factor from the processing study (1.5X) was used. 

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

included in Attachment 1. 

Tolerances have been established for kasugamycin (40CFR §180.614) in/on imported fruiting 

vegetables (crop group 8) at 0.04 ppm. A time-limited (Section 18) tolerance has also been 

established at 0.05 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be superseded by those listed above when the proposed new uses are registered. 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 

currently requested uses bear residues of kasugamycin (in other words, 100%CT). 
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4. Drinking Water Data

The drinking water residues used in this dietary risk assessment were provided by EFED 

(D376600; T. Dowen; 28 April 2011), and incorporated directly into the dietary assessment via 

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

EDWCs in surface water are 0.011562 ppm and 0.001178 ppm for acute and chronic scenarios, 

respectively. The EDWC in groundwater is 0.000116 ppm for all durations (see Table 1, below). 

The 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 EDWCs were obtained via exposure modeling which utilized the PRZM 

(Pesticide Root Zone Model) and EXAMS (EXposure Analysis Modeling System) models. 

These models and their descriptions are available at the EPA internet website via the web link,

http://www.epa.gov/oppefed1/models/water/. The PRZM/EXAMS modeling was based on 

application of kasugamycin to tomatoes 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 0.011562 0.001178* 0.000602

Ground Water (via SCI-GROW)

Walnut 0.000116 0.000116 0.000116

* EDWC used in the chronic dietary assessment. 

5. DEEM-FCIDTM Program and Consumption Information

The kasugamycin chronic dietary exposure assessment was conducted using DEEM-FCIDTM 

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

1998. The 1994-96, 1998 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 translation 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, 1998 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 US population, all 
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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 foodform (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 performed 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, and 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 exposure and risk 

are reported for all dietary analyses, regardless of the degree of refinement (unrefined through 

highly refined). However, for unrefined or slightly refined analyses, significant differences in 

user versus per capita exposure and risk are identified, 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 (D376608; W.T. Drew; 13 

July 2012). The available database is considered of high quality, and is adequate for assessment 

of risk for the proposed uses. 

The chronic reference dose (cRfD) is 0.11 mg/kg/day. The NOAEL of 11 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 compared 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 and 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, and maternal toxicity was seen at 1000 mg/kg/day (200 mg/kg/day). 
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The risk assessment team has confirmed that the selected doses and endpoints are appropriate to 

assess the currently proposed uses on fruiting vegetables, pome fruit, and walnuts. These 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

UFA= 10X

UFH= 10X

FQPA SF= 1X

Chronic RfD = 0.11

mg/kg/day

cPAD = 0.11

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: “Not 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 associated with lower environmentally relevant human 

exposures. 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. 

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 cPAD. The DEEM-FCIDTM analyses estimate the dietary exposure of the US 

population, and the various population subgroups. 

The results of the chronic analysis are summarized in Table 3, below. The exposure estimates 

are considered very conservative because tolerance-level residues, and 100% CT were assumed. 

As indicated in Table 3, the chronic risk estimates are not of concern for any of the population 

subgroups. 

Children 1-2 years of age are the most highly-exposed subgroup, utilizing 1.7% of the cPAD, 

while the general US population utilizes <1% of the cPAD. 
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TABLE 3 Summary of Chronic Dietary Exposure and Risk Estimates for Kasugamycin.

Population Subgroup*

[Years of Age]

cPAD (mg/kg/day) Dietary Exposure Estimate 

(mg/kg/day)

% cPAD

General US Population 0.11 0.000450 <1

All Infants [< 1] 0.11 0.001215 1.1

Children [1-2] 0.11 0.001839 1.7

Children [3-5] 0.11 0.001281 1.2

Children [6-12] 0.11 0.000647 <1

Youth [13-19] 0.11 0.000373 <1

Adults [20-49] 0.11 0.000310 <1

Adults [50+] 0.11 0.000279 <1

Females [13-49] 0.11 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 residues, and assumes that all crops with either 

current or proposed kasugamycin tolerances are treated (100%CT). These assumptions result in 

highly conservative, health-protective estimates of dietary exposure and risk. 

9. Conclusions

An unrefined chronic dietary assessment was conducted for all current and proposed uses of 

kasugamycin. There are no dietary exposure considerations that would preclude the 

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

and walnuts. Children 1-2 years of age are the most highly-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. 
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Attachment 1. Kasugamycin Residues Used for Chronic Dietary Exposure Estimates.

US Environmental Protection Agency

DEEM-FCID Version 2.03 (1994-1996, 1998 data)

Filename: KasugamycinDEEM060512Input.R98

Chemical: Kasugamycin

Chronic reference dose (RfD, Chronic): 0.11 mg/kg body weight/day

Date created or last modified: 6/5/2012 at 1002

 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 0F7689

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 11 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, nonbell, 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 0.150000 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 0F7689

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 0F7689
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Attachment 2. Summary of the Chronic Dietary Exposure and Risk Estimates for

Kasugamycin. 

US Environmental Protection Agency

DEEM-FCID Version 2.03 (1994-1996, 1998 data), Chronic analysis for KASUGAMYCIN

Residue file name: KasugamycinDEEM060512Input.R98

Adjustment factor #2 was NOT used.

Analysis date: 6/5/2012 at 1007

Residue file date: 6/5/2012 at 1002

Chronic reference dose (RfD, Chronic) = 0.11 mg/kg body weight/day

 Total Exposure by Population Subgroup

 Total Exposure

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

 Population mg/kg Percent of 

 Subgroup body 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 yrs 0.000346 0.3%

Females 13+ (preg/not nursing) 0.000399 0.4%

Females 13+ (nursing) 0.000342 0.3%

Males 13-19 yrs 0.000368 0.3%

Males 20+ yrs 0.000312 0.3%

Seniors 55+ 0.000279 0.3%

Children 1-2 yrs 0.001839 1.7%

Children 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%