Document ID: EPA-HQ-OPP-2008-0945-0006
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2009-12-09T05:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

     OFFICE OF	

PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

Date: 13 August 2009

MEMORANDUM

SUBJECT:	Clothianidin: Human Health Risk Assessment for Proposed Seed
Treatment Uses on Root and Tuber Vegetables (Group 1), Bulb Vegetables
(Group 3), Leafy Green Vegetables (Group 4A), Brassica Leafy Vegetables
(Group 5), Fruiting Vegetables (Group 8), Cucurbit Vegetables (Group 9),
and Cereal Grains (Group 15, except rice).

PC Code:  044309	DP Barcodes:  D357034

MRID No.:  See Below	Registration No.:  264-RNIR; 264-RNIE

Petition Nos.:  8F7416, 8F7413	Regulatory Action:  Section 3

Assessment Type:  Single Chemical Aggregate	Registration Case No.:  None

TXR No.:  None	CAS No.:  210880-92-5

Decision No.:  399566	40 CFR 180.586

FROM:	Michael A. Doherty, Ph.D., Chemist

		Alan Levy, Ph.D., Toxicologist

		Shih-Chi Wang, Ph.D., Biologist

		Risk Assessment Branch II

		Health Effects Division (7509P)

THROUGH:	Dennis McNeilly, Chemist

		Suku Oonnithan, Biologist

		Linnea Hansen, Ph.D., Toxicologist

		Richard A. Loranger, Ph.D., Senior Scientist

		Christina Swartz, Branch Chief

Risk Assessment Branch II

Health Effects Division (7509P)

TO:		Kable Davis/Venus Eagle (Team 01)

		Insecticide/Rodenticide Branch	

		Registration Division (7505P)

		Barbara Madden

		Risk Integration, Minor Use & Emergency Response Branch

		Registration Division (7505P)

MRID No.	Study Type

47483006	860.1340 Residue Analytical Method

47483007	860.1340 Independent Laboratory Validation

47483008	860.1360 Multi-Residue Method

47483009	860.1380 Storage Stability

47483012	860.1500 Potato

47483013	860.1500 Potato

47483014	860.1500 Root vegetables

47483015	860.1500 Bulb vegetables

47483017	860.1500 Leafy greens

47483018	860.1500 Brassica leafy vegetables

47483019	860.1500 Fruiting vegetables

47483020	860.1500 Cucurbit vegetables

47483021	860.1500 Wheat

47483022	860.1520 Potato

47483023	860.1520 Tomato

47483024	860.1520 Wheat

47524001	860.1900 Soybean

Table of Contents

  TOC \f  1.0	Executive Summary	  PAGEREF _Toc237924115 \h  4 

2.0	Ingredient Profile	  PAGEREF _Toc237924116 \h  6 

2.1	Summary of Registered/Proposed Uses	  PAGEREF _Toc237924117 \h  6 

2.2	Structure and Nomenclature	  PAGEREF _Toc237924118 \h  8 

2.3	Physical and Chemical Properties	  PAGEREF _Toc237924119 \h  8 

3.0	Hazard Characterization/Assessment	  PAGEREF _Toc237924120 \h  8 

4.0	Public Health and Pesticide Epidemiology Data	  PAGEREF
_Toc237924121 \h  9 

5.0	Dietary Exposure/Risk Characterization	  PAGEREF _Toc237924122 \h 
10 

5.1	Pesticide Metabolism and Environmental Degradation	  PAGEREF
_Toc237924123 \h  10 

5.1.8	Analytical Methodology	  PAGEREF _Toc237924124 \h  10 

5.1.9	Drinking Water Residue Profile	  PAGEREF _Toc237924125 \h  10 

5.1.10	Food Residue Profile	  PAGEREF _Toc237924126 \h  10 

5.1.11	International Residue Limits	  PAGEREF _Toc237924127 \h  12 

5.2	Dietary Exposure and Risk	  PAGEREF _Toc237924128 \h  14 

6.0	Residential (Non-Occupational) Exposure/Risk Characterization	 
PAGEREF _Toc237924129 \h  14 

7.0	Aggregate Risk Assessments and Risk Characterization	  PAGEREF
_Toc237924130 \h  14 

8.0	Cumulative Risk Characterization/Assessment	  PAGEREF _Toc237924131
\h  15 

9.0	Occupational Exposure/Risk Pathway	  PAGEREF _Toc237924132 \h  15 

9.1	Short- and Intermediate-Term Handler Risk	  PAGEREF _Toc237924133 \h
 15 

9.2	Short- and Intermediate-Term Post-Application Risk	  PAGEREF
_Toc237924134 \h  21 

10.0	Data Needs and Label Recommendations	  PAGEREF _Toc237924135 \h  21

10.1	Toxicology	  PAGEREF _Toc237924136 \h  21 

10.2	Residue Chemistry	  PAGEREF _Toc237924137 \h  21 

10.3	Occupational and Residential Exposure	  PAGEREF _Toc237924138 \h 
22 

References:	  PAGEREF _Toc237924139 \h  24 

 1.0	Executive Summary  TC \l1 "1.0	Executive Summary 

N.B.:  HED has recently completed an aggregate human health risk
assessment for clothianidin (M. Doherty, A. Levy, S. Wang.  D355373, 13
August 2009).  Many components of that assessment, including the hazard
assessment and dietary, residential, and aggregate exposure and risk
estimates, are applicable to this assessment of clothianidin.  For a
full discussion of these aspects of the risk assessment, please see that
document.

Clothianidin,
(E)-N-[(2-Chloro-5-thiazolyl)methyl]-N’-methyl-N”-nitroguanidine, is
a broad spectrum, systemic neonicotinoid insecticide (Group 4A
insecticide) and is identical to the major metabolite (CGA-322704) of
the active ingredient thiamethoxam.  Permanent tolerances are
established for residues of clothianidin in/on various plant and
livestock commodities [40 CFR §180.586].  Bayer Crop Science has
submitted petitions (PP#s 8F7416 and 8F7413) proposing use of a multiple
active ingredient (MAI), wettable powder (WP) formulation containing
56.25% clothianidin and 18.75% imidacloprid (Sepresto 75WS, EPA Reg. No.
264-RNIR) for use as a seed treatment for the control of various insects
on the following crops/crop groups:  root and tuber vegetables, bulb
vegetables, leafy green vegetables, Brassica leafy vegetables, fruiting
vegetables, cucurbit vegetables, and cereal grains, except rice.  Bayer
is also proposing use of another MAI formulation for seed treatment of
wheat, barley and triticale (Proceed™ Optimum; EPA Reg. No. 264-RNIE).
 This FlC formulation contains 0.128 lb/gal of clothianidin along with
three fungicides (prothioconazole, tebuconazole, and metalaxyl).  HED
has sufficient information to complete a human health risk assessment
for these requested uses.

The toxicological database for clothianidin is complete.  The available
data indicate that there are no consistent specific target organs in
mammals.  The majority of studies show decreases in body weights and
body weight gains.  More severe developmental (missing lobe of the lung
in the rabbit) and neurological effects in rats and mice are
attributable to exposure to clothianidin; these effects serve as the
basis for acute risk assessments.  Effects on body weight gain, delayed
sexual maturation, decreased thymus weights, and an increase in
stillbirths are the basis for assessing short-, intermediate-, and
long-term (chronic) exposures.  Based on the completeness of the
database, the observed effects, and the endpoints used for risk
assessment, the FQPA Safety Factor has been reduced to 1X, leaving the
100X safety factor to account for within-species (10X) and
across-species (10X) variability.  Clothianidin has been classified as
not likely to be carcinogenic to humans.

The submitted residue chemistry data are relatively complete.  HED is
recommending that label modifications be made prior to registering the
requested uses and that storage stability information be submitted as a
condition of registration.  Suitable analytical methods are available to
enforce tolerances for residues of clothianidin.

No chemical-specific data for assessing human exposures during pesticide
handling or post-application activities were submitted to the Agency in
support of the requested registrations of clothianidin.  HED used
standard assumptions to assess exposures for the proposed uses.  

The available data are adequate for assessment of exposure to
clothianidin, and HED has evaluated dietary, non-dietary (i.e.,
residential/recreational), and occupational risks associated with the
registered and requested uses of thiamethoxam.  For the dietary pathway,
thiamethoxam has been included as a source of exposure to clothianidin. 
All of the dietary, non-dietary, and occupational exposure estimates are
based on conservative, health-protective assumptions.  The exposure
estimates, especially when combined to take into account aggregate
(dietary + non-dietary) exposure, may over-estimate actual exposures
that are likely to occur.  Despite this, all aggregate risk estimates,
for all population groups are below HED’s level of concern.  With some
exceptions, the occupational risk estimates associated with the proposed
uses do not exceed HED’s level of concern.  For those activities with
risks of concern at baseline levels of personal protective equipment,
use of a dust-mist respirator or engineering controls (WP in
water-soluble packets) result in risk estimates below HED’s level of
concern.  Alternatively, application rates for these uses may be reduced
in order to obtain risk estimates that are not of concern.  Provided
labeling and packaging are changed or rates are lowered to mitigate
these occupational risk concerns, there are no human health risk issues
that preclude establishing tolerances and granting the requested
registrations for clothianidin.

Human Studies.  This risk assessment relies in part on data from studies
in which adult human subjects were intentionally exposed to a pesticide
or other chemical.  These studies, which comprise the Pesticide Handlers
Exposure Database (PHED) & Agricultural Re-Entry Task Force (ARTF), have
been determined to require a review of their ethical conduct, and have
received that review. The studies in PHED and ARTF were considered
appropriate (or ethically conducted) for use in risk assessments.

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

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

2.0	Ingredient Profile  TC \l1 "2.0	Ingredient Profile 

See M. Doherty, A. Levy, and S. Wang (D355373, 13 August 2009).

Provided the label revisions and revised Section F detailed in Section
10 are submitted, HED recommends for the requested soybean and potato
seed treatments, for foliar uses as detailed in the preceding table, and
for the tolerances detailed in Table 10.

2.1	Summary of Registered/Proposed Uses  TC \l2 "2.1	Summary of
Registered/Proposed Uses 

Permanent tolerances are established for residues of clothianidin in/on
a variety of plant commodities at levels ranging from 0.01 ppm in/on a
number of crops to 1.0 ppm in/on pome fruits [40 CFR §180.586(a)]. 
Tolerances for clothianidin have also been established in milk at 0.01
ppm.  Time-limited tolerances have been established at 0.02 ppm in/on
sugar beet roots and tops [40 CFR §180.586(b)]; these tolerances are
set to expire on 12/31/09.  In addition, tolerances for indirect or
inadvertent residues have been established for clothianidin at 0.02 ppm
in/on non-grass animal feeds, the forage, fodder and straw of cereal
grains, grass forage, fodder and hay, and soybean forage and hay [40 CFR
§180.586(d)].

Bayer CropScience (Bayer) has submitted petitions (PP# 8F7413 and
8F7416) proposing the use of a multiple active ingredient (MAI),
wettable powder (WP) formulation containing 56.25% clothianidin and
18.75% imidacloprid (Sepresto 75WS, EPA Reg. No. 264-RNIR) for use as a
seed treatment for the control of various insects on the following
crops/crop groups:  root and tuber vegetables, bulb vegetables, leafy
green vegetables, Brassica leafy vegetables, fruiting vegetables,
cucurbit vegetables, and cereal grains, except rice.  The proposed uses
on vegetable crops (except potato) are for seed treatments at maximum
use rates of 0.1-1.2 g ai/1000 seed, and the proposed maximum use rate
for potatoes is 12.5 g ai/100 kg seed pieces.  For cereal grains (except
rice), the proposed maximum use rate is 70 g ai/100 kg seed.  The WP
formulation is slurried with water and a seed colorant, and applied
using commercial seed treatment equipment.  Bayer is also proposing use
of another MAI formulation for seed treatment of wheat, barley and
triticale (Proceed™ Optimum; EPA Reg. No. 264-RNIE).  This FlC
formulation contains 0.128 lb/gal of clothianidin along with three
fungicides (prothioconazole, tebuconazole, and metalaxyl).  The maximum
proposed use rate for the FlC formulation is 7.5 g ai clothianidin/100
kg seed.  The use patterns associated with the requested uses are
summarized in Table 2.1.

Table 2.1.	Summary of Directions for Use of Clothianidin Seed
Treatments.

Applic. Timing, Type, and Equip.	Form.

[EPA Reg. No.]	Application Rates 1	Use Directions and Limitations 3

g ai/1000 seeds 	oz ai/1000 seeds	lb ai/A 2

	Root Vegetables (Group 1) 4

Seed treatment using commercial seed treatment equipment only	56.25% WP

[264-RNIR] 	Radish:  0.45

Carrot:  0.118	Radish:  0.01575 

Carrot:  0.0042	Radish: 0.50-0.67

Carrot:  0.10-0.25	Do not use treated seed for food, feed or oil
processing.

Bulb Vegetables (Group 3)

Seed treatment using commercial seed treatment equipment only	56.25% WP 

[264- RNIR]	Bulb onion:  0.18 

Green onion:  0.106

Leek: 0.20	Bulb onion:  0.006 

Green onion:  0.0037

Leek: 0.0071	Bulb onion:  0.06-0.19 

Green onion:  0.23-0.42

Leek: 0.30-0.35	Do not use treated seed for food, feed or oil
processing.

Leafy Green Vegetables (Subgroup 4A)

Seed treatment using commercial seed treatment equipment only	56.25% WP

[264- RNIR] 	Head Lettuce:  0.798 

Leaf Lettuce: 0.64 

Spinach: 0.16	Head Lettuce:  0.028 

Leaf Lettuce: 0.0225 

Spinach: 0.0055	Head Lettuce:  0.70-2.25

Leaf Lettuce:  0.68-2.26

Spinach:  0.09-0.21	Do not use treated seed for food, feed or oil
processing.

Brassica Leafy Vegetables (Group 5)

Seed treatment using commercial seed treatment equipment only	56.25% WP 

[264- RNIR]	Cabbage:  1.193

Broccoli:  1.193

Mustard Greens: 0.0995 	Cabbage: 0.0416

Broccoli:  0.0416

Mustard Greens: 0.0035	Cabbage:  0.06-0.44

Broccoli:  0.39-0.42

Mustard Greens: 0.03-0.16	Do not use treated seed for food, feed or oil
processing.

Fruiting Vegetables (Group 8)

Seed treatment using commercial seed treatment equipment only	56.25% WP

[264- RNIR] 	Tomato:  0.099

Pepper: 0.495	Tomato:  0.0035

Pepper: 0.0174 	Tomato:  0.02-0.06

Pepper:  0.04-0.21	Do not use treated seed for food, feed or oil
processing.

Cucurbit Vegetables (Group 9)

Seed treatment using commercial seed treatment equipment only	56.25% WP

[264- RNIR] 	Squash:  0.995

Melon:  0.995

Cucumber:  0.995	Squash:  0.034

Melon:  0.034

Cucumber:  0.034	Squash:  0.04

Melon:  0.02-0.11

Cucumber:  0.04-0.16	Do not use treated seed for food, feed or oil
processing.

Cereal Grains, except rice (Group 15)

Seed treatment using commercial seed treatment equipment only	56.25% WP 

[264- RNIR]	70 g ai/100 kg seed	1.125 oz ai/100 lbs seed 

	Corn:  0.007-0.011

Sorghum: 0.001-0.007

Millet:  0.011-0.025

Barley:  0.035-0.067

Oats:   0.034-0.090

Wheat:   0.021-0.105	Do not use treated seed for food, feed or oil
processing.

Wheat, Barley and Triticale

Seed treatment using on farm or commercial seed treatment equipment.  
0.128 lb/gal FlC

[264-RNIE]	7.5 g ai/100 kg seed	0.12 oz ai/100 lb seed	Barley: 
0.004-0.007

Wheat:   0.002-0.011	Do not use treated seed for food, feed or oil
processing.

Forage may be grazed or harvested 31 days after seeding.

Potato 

Seed treatment using commercial seed treatment equipment only	56.25% WP

[264- RNIR]	12.5 g ai/100 kg seed pieces	0.20 oz ai/100 lb seed pieces
potato:  0.163-0.325	Do not use treated seed for food, feed or oil
processing.

1	The seed treatment rates expressed in g ai/1000 seed and oz ai/1000
seed are the maximum use rates, unless otherwise indicated.  Although
the use directions cover entire crop groups, the use rates for
individual crops in each group were listed under each group.

2	The range of potential application rates expressed on a lb ai/A basis
were calculated by the reviewer using the maximum seed treatment rate
for each crop and information on the number of seeds/lb and planting
rates (lbs seed/A) from the ExpoSAC SOP 15 memo (3/2/2004).

3	For all uses, the label for the 56% WP specifies a maximum use rate of
0.375 lb ai/A per cropping cycle for clothianidin, regardless of
application type (seed, soil or foliar).  The label also specifies the
following rotational crop restrictions:  Areas planted with treated seed
may be replanted immediately with any crop having uses or tolerances for
clothianidin and imidacloprid.  Areas may also be replanted 30 days
later with soybeans, dried beans or dried peas.  Do not plant any other
crops in treated areas for at least one year after the treated seeds are
planted.   No maximum seasonal use rate or rotational crop restrictions
are specified on the label for the 0.128 lb/gal FlC.

4	Although the label specifies directions for “Root Vegetables”, the
label also cites Crop Group 1 and includes all vegetables in the Root
and Tuber Vegetables Crop Group. 

2.2	Structure and Nomenclature  TC \l2 "2.2	Structure and Nomenclature 

See M. Doherty, A. Levy, and S. Wang (D355373, 13 August 2009).

2.3	Physical and Chemical Properties

See M. Doherty, A. Levy, and S. Wang (D355373, 13 August 2009).

  TC \l2 "2.3	Physical and Chemical Properties 

3.0	Hazard Characterization/Assessment  TC \l1 "3.0	Hazard
Characterization/Assessment 

See M. Doherty, A. Levy, and S. Wang (D355373, 13 August 2009).  The
endpoints and points of departure for human health risk assessments are
summarized in Tables 3.0a and 3.0b, below.

Table 3.0a.  Summary of Toxicological Doses and Endpoints for
Clothianidin for Use in Dietary and Non-Occupational Human Health Risk
Assessments.

Exposure/

Scenario	Point of Departure	Uncertainty/

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

Acute Dietary

Females age 

13-49 	NOAEL =  

25 mg/kg/day	UFA = 10X

UFH = 10X

SFFQPA =1

 	aRfD=0.25 mg/kg/day

aPAD=0.25 mg/kg/day	Rabbit developmental  study 

LOAEL = 75 mg/kg/day based on increased litter incidence of a missing
lobe of the lung

Acute Dietary

General population	NOAEL = 

25 mg/kg/day	UFA = 10X

UFH = 10X

SFFQPA  = 1	aRfD = 0.25

mg/kg/day

aPAD 0.25

mg/kg/day	Special neurotoxicity/pharmacol

study in mice 

LOAEL = 50 mg/kg/day based on transient signs of decreased spontaneous
motor activity, tremors and deep respirations

Chronic Dietary

All populations including infants and children	NOAEL= 

9.8 mg/kg/day  	UFA = 10X

UFH = 10X

SFFQPA =1	cRfD=0.098 mg/kg/day

cPAD=0.098 mg/kg/day	2-Generation reproduction study 

LOAEL = 31.2 mg/kg/day based on decreased body weight gains and delayed
sexual maturation, decreased absolute thymus weights in F1 pups and
increased stillbirths in both generations

Incidental Oral (short and intermediate term)	NOAEL= 

9.8 mg/kg/day	UFA= 10X

UFH= 10X

SFFQPA=1	MOE= 100 (residential and occupational)	2-Generation
reproduction study 

LOAEL= 31.2  mg/kg/day based on decreased body weight gains and delayed
sexual maturation, decreased absolute thymus weights in F1 pups 

Dermal (all durations) 	Oral study NOAEL= 

9.8 mg/kg/day

(dermal absorption = 1%)	UFA= 10X

UFH= 10X

SFFQPA=1	MOE= 100 (residential and occupational)	2-Generation
reproduction study 

LOAEL = 31.2 mg/kg/day based on  decreased body weight gains and delayed
sexual maturation, decreased absolute thymus weights in F1 pups and
increased stillbirths in both generations

Inhalation (all durations)

	Oral study NOAEL= 

9.8 mg/kg/day

(inhalation absorption = 100% of oral absorption)	UFA= 10X

UFH= 10X

SFFQPA=1	MOE= 100 (residential and occupational)	2-Generation
reproduction study

LOAEL = 31.2 mg/kg/day based on decreased body weight gains and delayed
sexual maturation, decreased absolute thymus weights in F1 pups and
increased stillbirths in both generations

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

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

Table 3.0b.  Summary of Toxicological Doses and Endpoints for
Clothianidin for Use in Occupational Human Health Risk Assessments.

Exposure/

Scenario	Point of Departure	Uncertainty/FQPA Safety Factors	Level of
Concern for Risk Assessment	Study and Toxicological Effects

Dermal (all durations) (Adults)	Oral study NOAEL= 

9.8 mg/kg/day

(dermal absorption = 1%)	UFA= 10X

UFH= 10X

SFFQPA=1	MOE= 100 	2-Generation reproduction study 

LOAEL = 31.2 mg/kg/day based on  decreased body weight gains and delayed
sexual maturation, decreased absolute thymus weights in F1 pups and
increased stillbirths in both generations

Inhalation (all durations)

	Oral study NOAEL= 

9.8 mg/kg/day

(inhalation absorption = 100% of oral absorption)	UFA= 10X

UFH= 10X

SFFQPA=1	MOE= 100	2-Generation reproduction study

LOAEL = 31.2 mg/kg/day based on decreased body weight gains and delayed
sexual maturation, decreased absolute thymus weights in F1 pups and
increased stillbirths in both generations

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

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

4.0	Public Health and Pesticide Epidemiology Data  TC \l1 "4.0	Public
Health and Pesticide Epidemiology Data 

No public health or epidemiological data were used for this risk
assessment.

5.0	Dietary Exposure/Risk Characterization  TC \l1 "5.0	Dietary
Exposure/Risk Characterization 

5.1	Pesticide Metabolism and Environmental Degradation  TC \l2 "5.1
Pesticide Metabolism and Environmental Degradation 

See M. Doherty, A. Levy, and S. Wang (D355373, 13 August 2009).  

Table 5.1.  Summary of Metabolites and Degradates to be included in the
Risk Assessment and Tolerance Expression.

Matrix	Residues included in Risk Assessment	Residues included in
Tolerance Expression

Plants

	Primary Crop	Leafy and Root/Tuber Vegetables:  Parent + TMG

Other crops: Parent	Parent

	Rotational Crop	Parent, TZNG, MNG	Parent

Livestock

	Ruminant	Parent, TZU, TZG, TZNG, ATMG-Pyr	Parent

	Poultry	Parent, TZU, TZG, TZNG, ATG-Ac	Parent

Drinking Water	Parent	Not Applicable

5.1.8	Analytical Methodology  TC \l3 "5.1.8	Analytical Methodology 

Adequate methods are available for enforcing tolerances for residues of
clothianidin on plant commodities.  The residue data on clothianidin,
TMG and TZNG in the submitted field trials, processing studies, and
rotational crop field trials were collected using adequate LC-MS/MS
methods.

Bayer has proposed an adequate LC-MS/MS method (Method No.
TI-002-P05-001) for enforcing possible tolerances for the combined
residues of clothianidin and TMG in/on root and tuber vegetables, leafy
vegetables, and Brassica vegetables.   Adequate validation data were
provided for this method, and the method has undergone a successful ILV
trial.

5.1.9	Drinking Water Residue Profile TC \l3 "5.1.9	Drinking Water
Residue Profile 

See M. Doherty, A. Levy, and S. Wang (D355373, 13 August 2009). 
Estimates of clothianidin in drinking water, based on the use on turf,
are summarized in Table 5.1.9.

Table 5.1.9	Summary of Estimated Surface Water and Groundwater
Concentrations for Clothianidin.

Scenario	Surface Water Conc., ppb a	Groundwater Conc., ppb b

Acute	7.29	5.88

Chronic (non-cancer)	1.35	5.88

a From the Tier I FIRST model.  Input parameters are based on use of
clothianidin on turf grass.

b From the SCI-GROW model assuming a maximum seasonal use rate of 0.4 lb
ai/A, a Koc of 84, and a half-life of 744 days.

5.1.10	Food Residue Profile  TC \l3 "5.1.10	Food Residue Profile 

The submitted field trial data reflecting seed treatment applications of
clothianidin using WP or FlC formulations are adequate.  An adequate
number of field trials were conducted on the required representative
crops in the appropriate geographic regions.  All tests were conducted
at ~1x the proposed use rates, with the exceptions of the potato and
wheat field trials.   The U.S. potato field trials were conducted at
1.6x the proposed rate, the Canadian potato field trials were conducted
at 1x the proposed rate, and the wheat field trials were conducted at
1.8x the proposed rate.  Samples of each RAC from all the field trials
were analyzed using adequate LC-MS/MS methods, and available storage
stability data support the sample storage durations and conditions.

Table 5.1.10.  Summary of Residue Data from Crop Field Trials Using Seed
Treatments of Clothianidin (WP or FlC).

Crop matrix	Analyte	Applic. Rate 1	PHI (days)	Residue Levels (ppm) 2

n	Min.	Max.	HAFT 3	Median	Mean	Std. Dev.

Root Vegetables:  proposed use = carrot – 0.118 g ai/1000 seed, radish
– 0.45 g ai/1000 seed

Carrot	Clothianidin	0.12

(0.023-0.342)	90-196

90-196	16	<0.00	0.011	0.011	0.010	0.010	<0.001

	TMG

	16	<0.01	<0.01	<0.010	0.010	0.010	NA

Radish roots	Clothianidin	0.50

(0.087-0.429)	34-60

34-60	10	<0.01	0.625	0.528	0.016	0.124	0.219

	TMG

	10	<0.01	<0.01	<0.01	0.010	0.010	NA

Radish tops	Clothianidin	0.50

(0.087-0.429)	34-60

34-60	10	<0.01	0.343	0.339	0.050	0.114	0.130

	TMG

	10	<0.01	0.113	0.112	0.058	0.057	0.040

Potato – 12.5 g ai/100 kg seed pieces or 0.0125 lb ai/100 lb seed
pieces

Potato 

(U.S. tests)	Clothianidin	19-24 g ai/100 kg seed pieces

(0.33-0.42)	79-143	32	<0.010	0.101	0.086	0.029	0.037	0.026

	TMG

	32	<0.010	<0.010	0.010	0.010	0.010	NA

Potato (Canadian tests)	Clothianidin	12 g ai/100 kg seed pieces 	90	10
<0.020	0.240	0.225	0.050	0.079	0.079

Bulb Vegetables:  proposed use = bulb onion – 0.18 g ai/1000 seed,
green onion – 0.106 g ai/1000 seed

Bulb onion	Clothianidin	0.20

(0.019-0.094)	106-269	12	<0.01	0.017	0.014	0.010	0.011	0.002

	TMG

106-269	12	<0.01	<0.01	<0.01	0.010	0.010	NA

Green onion 	Clothianidin	0.12

(0.028-0.145)	90-153	6	0.013	0.142	0.128	0.068	0.074	0.048

	TMG

90-153	6	<0.01	0.022	0.017	0.012	0.014	0.005

Leafy Greens (Subgroup 4A): proposed uses = head lettuce – 0.8 g
ai/1000 seed, leaf lettuce – 0.64 g ai/1000 seed, spinach -
0.16 g ai/1000 seed)

Head lettuce	Clothianidin	0.792-0.804

(0.027-0.508)	53-143	12	<0.01	0.091	0.082	0.010	0.022	0.028

	TMG

53-143	12	<0.01	0.024	0.023	0.010	0.012	0.005

Leaf lettuce	Clothianidin	0.644-0.654

(0.079-1.41)	45-67	12	0.033	0.349	0.315	0.010	0.085	0.125

	TMG

45-67	12	<0.01	0.155	0.149	0.027	0.042	0.051

Spinach	Clothianidin	0.161

(0.033-0.106)	47-96	12	<0.01	0.078	0.066	0.013	0.026	0.023

	TMG

47-96	12	<0.01	0.021	0.017	0.010	0.011	0.003

Brassica Leafy Vegetables:   proposed uses = broccoli and cabbage - 1.19
g ai/1000 seed, mustard greens - 0.1 g ai/1000 seed

Broccoli	Clothianidin	1.19-1.21

(0.046-0.339)	74-195

74-195	12	<0.01	0.409	0.329	0.010	0.063	0.129

	TMG

	12	<0.01	0.130	0.103	0.010	0.026	0.038

Cabbage	Clothianidin	1.21

(0.046-0.330)	74-177

74-177	12	<0.01	<0.01	<0.01	0.010	0.010	NA

	TMG

	12	<0.01	<0.01	<0.01	0.010	0.010	NA

Mustard greens	Clothianidin	0.100-0.101

(0.015-0.132)	28-62

28-62	10	<0.01	0.011	0.010	0.010	0.010	0.0

	TMG

	10	<0.01	0.024	0.018	0.010	0.013	0.005

Fruiting Vegetables:  proposed use = tomato – 0.1 g ai/1000 seed,
pepper – 0.5 g ai/1000 seed

Tomato	Clothianidin	0.10

(0.0008-0.0038)	112-174	24	<0.01	<0.01	<0.01	0.01	0.01	NA

Bell pepper

0.50

(0.002-0.036)	90-196	12	<0.01	<0.01	<0.01	0.01	0.01	NA

Non-Bell pepper (fresh)

0.50

(0.011-0.016)	119-149	6	<0.01	<0.01	<0.01	0.01	0.01	NA

Non-Bell pepper (dried)

	130-149	6	<0.01	0.013	0.013	0.010	0.011	0.001

Cucurbit Vegetables:  proposed use = 1.0 g ai/1000 seeds

Cucumber	Clothianidin	1.0

(0.005-0.081)	46-53	12	<0.01	<0.01	0.01	0.01	0.01	NA

Muskmelon

1.0

(0.014-0.064)	75-98	12	<0.01	<0.01	0.01	0.01	0.01	NA

Summer squash

1.0

(0.010-0.062)	41-49	10	<0.01	<0.01	0.01	0.01	0.01	NA

Wheat:  proposed use = 70 g ai/100 kg seed

Wheat forage	Clothianidin	125 g ai/100 kg seed 

(0.067-0.171)	31-245	40	<0.01	0.273	0.253	0.076	0.087	0.075

Wheat hay

	56-277	40	<0.01	0.085	0.071	0.011	0.019	0.016

Wheat grain

	86-307	40	<0.01	<0.01	<0.01	0.010	0.010	NA

Wheat straw

	86-307	40	<0.01	0.043	0.040	0.010	0.014	0.009

1	Except for wheat and potatoes, the application rates are expressed in
g ai/1000 seed.  The value in parentheses is the equivalent field use
rates (lb ai/A) which were calculated by the reviewer based on the
planting densities (seeds/A) used in the field trials.  Regardless of
application type (seed, soil or foliar) the label-specified maximum
seasonal use rate for clothianidin is 0.375 lb ai/A.

2	The LOQ is 0.01 ppm.  Residues <LOQ were estimated to be 0.01 ppm for
all calculations.  

3	HAFT = Highest Average Field Trial.

NA= Not applicable

No major deficiencies were noted in the subject petition that would
preclude establishing permanent tolerances for residues of clothianidin
on the proposed commodities and crop groups.  However, the petitioner
should resolve the minor deficiencies noted in Section 10.  

5.1.11	International Residue Limits TC \l3 "5.1.11	International Residue
Limits 

Except for potatoes, there are currently no established or proposed
Codex, Canadian, or Mexican maximum residue limits (MRLs) for
clothianidin on the requested crops/crop groups.  For potato
commodities, HED’s recommended tolerances are in accord with
established/recommended Canadian MRLs.  Therefore, harmonization with
international MRLs is not an issue with this petition.  An International
Residue Limit Status Sheet follows.

INTERNATIONAL RESIDUE LIMIT STATUS

Chemical Name:
(E)-N-[(2-Chloro-5-thiazolyl)methyl]-N’-methyl-N”-nitroguanidine
Common Name: Clothianidin	X Proposed tolerances

 Reevaluated tolerance

 Other	Date: 4/25/09

Codex Status (Maximum Residue Limits)	U. S. Tolerances

X No Codex proposal step 6 or above

 No Codex proposal step 6 or above for the crops requested 	Petition
Numbers: 8F7413 and 8F7416

DP Numbers: 357455 and 357454

 No Limits

 No Limits for the crops requested	X  No Limits

   No Limits for the crops requested

Residue definition: Clothianidin	Residue definition:  NA

Crop(s)	MRL (mg/kg)	Crop(s)	MRL (mg/kg)

  SEQ CHAPTER \h \r 1 Field corn grain	0.01

Popcorn grain	0.01

Rapeseed (canola)	0.01

Sweet corn kernel plus cob with husk removed	0.01

Milk	0.01

Notes/Special Instructions:  Potato commodities were recently given MRLs
by Canada, as follows:  Tubers (0.3 ppm), chips (0.6 ppm), and
granules/flakes (1.5 ppm).  PMRA (Canada) is currently reviewing a
petition to establish tolerances on stone fruit, which includes peaches.

5.2	Dietary Exposure and Risk TC \l2 "5.2	Dietary Exposure and Risk 

See M. Doherty (D364363, 11 August 2009).  The results of that
assessment are summarized in Table 5.2 for convenience.

Table 5.2.  Summary of Dietary Exposure and Risk Estimates for
Clothianidin.

Population Subgroup	Acute (95th Pecentile of Exposure)	Chronic

	Exposure, mg/day	Risk, % aPAD	Exposure, mg/day	Risk, % cPAD

U.S. Population (total)	0.015019	6	0.004582	5

All infants (< 1 year)	0.048266	19	0.012680	13

Children 1-2 yrs	0.057317	23	0.018429	19

Children 3-5 yrs	0.039089	16	0.012188	12

Children 6-12 yrs	0.018014	7	0.005801	6

Youth 13-19 yrs	0.011055	4	0.003194	3

Adults 20-49 yrs	0.010157	4	0.003229	3

Adults 50+ yrs	0.010121	4	0.003438	4

Females 13-49 yrs	0.010797	4	0.003325	3

The population subgroup(s) with the highest exposure/risk estimates are
shown in bold.

6.0	Residential (Non-Occupational) Exposure/Risk Characterization  TC
\l1 "6.0	Residential (Non-Occupational) Exposure/Risk Characterization 

See M. Doherty, A. Levy, and S. Wang (D355373, 13 August 2009).  All
risk estimates are below HED’s level of concern.  Residential exposure
estimates are summarized in Table 6.0.

Table 6.0.  Summary of Residential Post-Application Exposure and Risk
Estimates.

Activity	Exposure (Dose)

mg a.i./kg bw/day	MOE

Adult dermal application	0.000026	370000

Adult dermal post-application turf contact	0.00108	9100

Adult golfer post-application turf contact	0.000075	130000

Adult combined	0.001181	8300

Toddler oral hand to mouth from contacting treated turf	0.0059	1700

Toddler incidental oral ingestion of treated soil	0.00002	490000

Toddler dermal post-application turf contact	0.00155	6300

Toddler combined	0.00747	1300

7.0	Aggregate Risk Assessments and Risk Characterization  TC \l1 "7.0
Aggregate Risk Assessments and Risk Characterization 

See M. Doherty, A. Levy, and S. Wang (D355373, 13 August 2009).  All
risk estimates are below HED’s level of concern (Table 7.0).

Table 7.0.  Summary of the Short- and Intermediate-Term Aggregate
Exposure and Risk Estimates for Clothianidin.

Population Subgroup	Total Residential Exposure, mg/kg/day	Chronic
Dietary Exposure, mg/kg/day	Aggregate Exposure1, mg/kg/day	MOE2

U.S. Population (total)	0.001181	0.004582	0.005763	1700

All infants (< 1 year)	0.00747	0.012680	0.020150	480

Children 1-2 yrs	0.00747	0.018429	0.025899	380

Children 3-5 yrs	0.00747	0.012188	0.019658	500

Children 6-12 yrs	0.001181	0.005801	0.006982	1400

Youth 13-19 yrs	0.001181	0.003194	0.004375	2200

Adults 20-49 yrs	0.001181	0.003229	0.004410	2200

Adults 50+ yrs	0.001181	0.003438	0.004619	2100

Females 13-49 yrs	0.001181	0.003325	0.004506	2200

The population subgroup with the highest estimated exposure/risk is
bolded.

1 Aggregate Exposure = Residential Exposure + Chronic Dietary Exposure

2 Aggregate MOE = NOAEL (9.8 mg/kg/day) ÷ Aggregate Exposure
(mg/kg/day)

8.0	Cumulative Risk Characterization/Assessment  TC \l1 "8.0	Cumulative
Risk Characterization/Assessment 

See M. Doherty, A. Levy, and S. Wang (D355373, 13 August 2009).

9.0	Occupational Exposure/Risk Pathway  TC \l1 "9.0	Occupational
Exposure/Risk Pathway 

Based on the proposed use patterns, handler and post-application
exposures to clothianidin may occur.  Exposures are not expected to
exceed short- (< 30 days) or intermediate-term (< 6 months) durations.

9.1	Short- and Intermediate-Term Handler Risk  TC \l2 "9.1	Short- and
Intermediate-Term Handler Risk 

Handler exposures may occur during seed-treatment uses.  Exposure and
risk estimates for handlers are based on SOPs developed by HED’s
Exposure Science Advisory Council.  Handler exposure and risk estimates
are summarized in Table 9.1.1, below, for the seed treatment uses,
respectively.  For a complete description of the handler exposure
analysis, see D363338 (S. Wang, 16 July 2009).

There are five handler scenarios that are expected to result in the
highest exposure for the proposed uses:

Loading (Open)/Applying Liquid for Seed Treatment (Scenario 1) 

Sewing Seeds after Seed Treatment (Scenario 2)

Bagging Seeds after Seed Treatment (Scenario 3)

Multiple Activities Worker for Seed Treatment (Scenario 4)

On-Farm Seed Treatment (Scenario 5)

Except for a few MOEs (for onion-bunching, spinach, squash, millet, and
potato seed pieces), all other MOEs calculated for commercial seed
treatment loader/applicator are smaller than 100 at the baseline (single
layer + gloves) level (range = 4 ~ 400) and therefore exceed HED level
of concern.  The MOEs for lettuces (head/leaf ) and cabbage seed
treatment loader/applicator are still smaller than 100 at the PPE
(single layer + gloves plus dust-mist respirator) level.  The MOEs for
lettuces (head/leaf ) and cabbage seed treatment loader/applicator are
greater than 100 at the engineering control (wettable powder in water
soluble packets) level.  

All MOEs calculated for sewer and bagger are greater than 100 at the
baseline level (single layer, no gloves) and therefore do not exceed HED
level of concern.  Except for lettuce (head/leaf; MOEs of 86-88), all
other MOEs calculated for multiple activities seed treatment workers are
greater than 100 at the baseline level (single layer + gloves).     

All MOEs calculated for on-farm seed treatment handlers do not exceed
HED level of concern at the baseline (single layer + gloves) level.  The
HED level of concern is an MOE of 100.

Table 9.1.  Occupational Handler Risk Estimates for the Requested Seed
Treatment Uses of Clothianidin (Commercial Production Uses).

Exposure Scenario (Scenario #)	

Mitigation Level	

Dermal Unit Exposure (mg/lb ai)	

Inhalation Unit Exposure   (mg/lb ai)	

Seed Species	

Application Rate

(lb ai  per lb seed)	

Amount Treateda

(lb seed trt per day)	

Daily

Dermal

Dose b (mg/kg/day)	

Daily

Inhalation

Dosec (mg/kg/day)	

Combined Daily Dosed  (mg/kg/day)	

MOEe

Loader/Applicator

Loading/Applying

Wettable Powder (open bag)  for 

Seed Treatment (1)

	Baseline =Single Layer, Gloves	0.17	0.04342	Radish 

Carrot 	0.0400

0.0944	5,500

5,500	0.005343

0.012609	0.136463

0.322052	0.141806

0.334661	69

29

Onion (bulb)

Leek

Onion(bunching)	0.0450

0.0698

0.0265	5,500

5,500

5,500	0.006011

0.009323

0.00354	0.153521

0.238128

0.090407	0.159532

0.24745

0.093947	61

40

100

Lettuce (head)

Lettuce (leaf)

Spinach	0.7166

0.7040

0.0155	5,500

5,500

5,500	0.095717

0.094034

0.00207	2.444732

2.401746

0.052879	2.540449

2.49578

0.054949	4

4

180

Squash

Melon

Cucumber	0.00696

0.04572

0.0398	5,500

5,500

5,500	0.00093

0.006107

0.005316	0.023745

0.0155977

0.135781	0.024675

0.0217047

0.141097	400

60

69

Tomato

Pepper	0.0337

0.0742	5,500

5,500	0.004501

0.009911	0.11497

0.253139	0.119471

0.26305	82

37

Cabbage 

& Broccoli

Mustard green	0.3775

0.0526	5,500

5,500	0.050423

0.007026	1.287868

0.179449	1.338291

0.186475	7

53

Barley, Oats,

Wheat, Triticale, 

Rye, Sorghum

Corn

Millet	0.00068	718,000

550,000

88,000	0.011857

0.009083

0.001453	0.302848

0.231987

0.037118	0.314705

0.24107

0.038571	31

41

250

Potato sd pieces	0.00013	1,000,000	0.003157	0.080637	0.083794	120

Loading/Applying

Wettable Powder (open bag)  for 

Seed Treatment (1a)

	PPE

=Single Layer, Gloves

+

Dust-Mist

Respirator	0.17	0.0086	Carrot	0.0944	5,500	0.012609	0.063787	0.076396
130

Cabbage	0.3775	5,500	0.050423	0.255082	0.305505	32

Lettuces (both)	≥0.704	5,500	≥0.094034	≥0.475743	≥0.569777	≤17

Barley etc.	0.00086

	718,000	0.011857	0.059984	0.071841	140

Corn

550,000	0.009083	0.045949	0.055032	180

Loading/Applying Wettable Power (Water Soluable Packets) (1b)	En.
Control

(Single Layer, 

No Gloves)	0.021	0.00024	Lettuce (head)	0.7166	5,500	0.011824	0.013513
0.025337	390

Cabbage

Lettuce (leaf)	0.3775  0.7040	5,500	<0.011824	<0.013513	<0.025337	>390



Sewer

Sewing Seeds after Seed treatment (2)	Single Layer, 

No Gloves	0.0062	0.00023	Radish 

Carrot 	0.0400

0.0944	5,500

5,500	0.000195

0.00046	0.000723

0.001746	0.000918

0.002206	11,000

4,500

Onion (bulb)

Leek

Onion(bunching)	0.0450

0.0698

0.0265	5,500

5,500

5,500	0.000219

0.00034

0.000129	0.000813

0.001261

0.000479	0.001032

0.001601

0.000608	9,500

6,100

16,000

Lettuce (head)

Lettuce (leaf)

Spinach	0.7166

0.7040

0.0155	5,500

5,500

5,500	0.003491

0.003429

0.0000755	0.01295

0.012722

0.00028	0.016441

0.016151

0.0003555	600

610

28,000

Squash

Melon

Cucumber	0.00696

0.04572

0.0398	5,500

5,500

5,500	0.0000339

0.000223

0.000194	0.000126

0.000826

0.000719	0.0001599

0.001049

0.000913	61,000

9,300

11,000

Tomato

Pepper	0.0337

0.0742	5,500

5,500	0.000164

0.000361	0.000609

0.001341	0.000773

0.001702	13,000

5,800

Cabbage 

& Broccoli

Mustard green	0.3775

0.0526	5,500

5,500	0.001839

0.000256	0.006822

0.000951	0.008661

0.001207	1,100

8,100

Barley, Oats,

Wheat, Triticale, 

Rye, Sorghum

Corn

Millet	0.00068	718,000

550,000

88,000	0.000432

0.000331

0.000053	0.001604

0.001229

0.000197	0.002036

0.00156

0.00025	4,800

6,300

39,000

Bagger

800,000

Bagging Seeds after Seed treatment (3)	Single Layer, 

No Gloves	0.0091	0.00016	Radish 

Carrot 	0.0400

0.0944	5,500

5,500	0.000286

0.000675	0.000503

0.001187	0.000789

0.001862	12,000

5,300

Onion (bulb)

Leek

Onion(bunching)	0.0450

0.0698

0.0265	5,500

5,500

5,500	0.000322

0.000499

0.000189	0.000566

0.000877

0.000333	0.000888

0.001376

0.000522	11,000

7,100

19,000

Lettuce (head)

Lettuce (leaf)

Spinach	0.7166

0.7040

0.0155	5,500

5,500

5,500	0.005124

0.005034

0.000111	0.009009

0.00885

0.000195	0.014133

0.013884

0.000306	700

710

32,000

Squash

Melon

Cucumber	0.00696

0.04572

0.0398	5,500

5,500

5,500	0.0000498

0.000327

0.000285	0.0000875

0.000575

0.0005	0.0001373

0.000902

0.000785	71,000

11,000

12,000

Tomato

Pepper	0.0337

0.0742	5,500

5,500	0.000241

0.000531	0.000424

0.000933	0.000665

0.001464	15,000

6,700

Cabbage 

& Broccoli

Mustard green	0.3775

0.0526	5,500

5,500	0.002699

0.000376	0.004746

0.000661	0.007445

0.001037	1,300

9,400

Barley, Oats,

Wheat, Triticale, 

Rye, Sorghum

Corn

Millet	0.00068	718,000

550,000

88,000	0.000635

0.000486

0.0000778	0.001116

0.000855

0.000137	0.001751

0.001341

0.0002148	5,600

7,300

46,000



Multiple Activities Worker

800,000

Multiple Activities for Seed treatment (4)	Single Layer, Gloves	0.042
0.0016	Radish 

Carrot 	0.0400

0.0944	5,500

5,500	0.00132

0.003115	0.005029

0.011867	0.006349

0.014982	1,500

650

Onion (bulb)

Leek

Onion(bunching)	0.0450

0.0698

0.0265	5,500

5,500

5,500	0.001485

0.002303

0.000875	0.005657

0.008775

0.003331	0.007142

0.011078

0.004206	1,400

880

2,300

Lettuce (head)

Lettuce (leaf)

Spinach	0.7166

0.7040

0.0155	5,500

5,500

5,500	0.023648

0.023232

0.000512	0.090087

0.088503

0.001949	0.113735

0.111735

0.002461	86

88

4,000

Squash

Melon

Cucumber	0.00696

0.04572

0.0398	5,500

5,500

5,500	0.00023

0.001509

0.001313	0.000875

0.005748

0.005003	0.001105

0.007257

0.006316	8,900

1,400

1,600

Tomato

Pepper	0.0337

0.0742	5,500

5,500	0.001112

0.002449	0.004237

0.009328	0.005349

0.011777	1,800

830

Cabbage 

& Broccoli

Mustard green	0.3775

0.0526	5,500

5,500	0.012458

0.001736	0.047457

0.006613	0.059915

0.008349	160

1,200

Barley, Oats,

Wheat, Triticale, 

Rye, Sorghum

Corn

Millet	0.00068	718,000

550,000

88,000	0.002929

0.002244

0.000359	0.01116

0.008549

0.001368	0.014089

0.010793

0.001727	700

910

5,700

a	Daily amounts treated values are based on exposure SAC Policy #15 or
the information provided by the Registrant through Registration
Division. 

b	Daily dermal dose (mg/kg/d) =  [unit dermal exposure (mg/lb ai) ×
dermal absorption (0.01) × application rate (lb ai/lb seed) × daily
amounts treated /  body weight (70 kg).

c	Daily inhalation dose (mg/kg/d) = (unit exposure (mg/lb ai) ×
application. rate (lb ai/lb seed) × daily amounts treated / body weight
(70 kg).

d	Combined daily dose (mg/kg/d) =  Daily dermal dose (mg/kg/d) + Daily
inhalation dose (mg/kg/d).

e	MOE = NOAEL (9.8  mg/kg/d) / combined daily dose.  UF = 100.



Table 9.2.  Occupational Handler Risk Estimates for the Requested
Seed-Treatment Use of Clothianidin (On-Farm Uses).

Exposure Scenario (Scenario #)	Mitigation Level	Dermal Unit Exposure
(mg/lb ai)	Inhalation Unit Exposure   (mg/lb ai)	Seed 
Category--Representative

Seed Species	Application Rate

(lb ai  per lb seed)	Amount Treateda

(lb seed trt per day)	Daily

Dermal

Dose b (mg/kg/day)	Daily

Inhalation

Dosec (mg/kg/day)	Combined Daily Dosed (mg/kg/day) 	MOEe  

On-Farm Seed Treatment Handlers

On-Farm

Seed Treatment (5)	Single Layer, Gloves	12.6	0.0012	Barley 

Oats

Wheat 

Triticale, Rye Sorghum

Corn

Millet	0.00068	19,000

26,000

30,000

20,000

800

3,000

2,800	< 0.03672

< 0.03672

0.03672

< 0.03672

< 0.03672

< 0.03672

< 0.03672	< 0.00035

< 0.00035

0.00035

< 0.00035

< 0.00035

< 0.00035

< 0.00035	< 0.0371

< 0.0371

0.0371

< 0.0371

< 0.0371

< 0.0371

< 0.0371	> 260

> 260

260

> 260

> 260

> 260

> 260

Potato seed pieces	0.00013	60,000	0.01404	0.000134	0.014174	690

a	Daily amounts treated values are based on exposure SAC Policy #15 or
the information provided by the Registrant through Registration
Division. 

b	Daily dermal dose (mg/kg/d) =  [unit dermal exposure (mg/lb ai) ×
dermal absorption (0.01) × application rate (lb ai/lb seed) × daily
amounts treated /  body weight (70 kg).

c	Daily inhalation dose (mg/kg/d) = (unit exposure (mg/lb ai) ×
application. rate (lb ai/lb seed) × daily amounts treated / body weight
(70 kg).

d	Combined daily dose (mg/kg/d) =  Daily dermal dose (mg/kg/d) + Daily
inhalation dose (mg/kg/d).

e	MOE = NOAEL (9.8 mg/kg/d) / combined daily dose.  UF = 100.			



9.2	Short- and Intermediate-Term Post-Application Risk  TC \l2 "9.2
Short- and Intermediate-Term Post-Application Risk 

Post-application exposures may occur from the handling of treated seeds
(secondary seed handling).  As with the handler occupational exposure
and risk estimates, the post-application risk estimates are detailed in
D363338 (S. Wang, 16 July 2009).  All post-application MOEs are greater
than or equal to 100 and reflect risk estimates that are below HED’s
level of concern.  The post-application MOEs are summarized in Tables
9.2.1.

Table 9.2.1.  Risk Estimate for Secondary Seed Handlers of Treated Seed.

Exposure Scenario (Scenario #)	

Mitigation Level	

Seed  Category--Representative

Seed Species	

Application Rate

(lb ai/lb seed)	

Amount Planteda

(lb seed/day)	

Daily

Dermal

Dose b (mg/kg/day)	

Daily

Inhalation

Dosec (mg/kg/day)	

Combined Daily Dosed (mg/kg/day) 	

MOEe  

Secondary Seed Handlers: planting seeds in the field	Single Layer,
Gloves	Radish 

Carrot 	0.0400

0.0944	1,600

1,600	0.0023

0.0054	0.0031

0.0073	0.0054

0.0127	1,800

770

Onion (bulb)

Leek

Onion(bunching)	0.0450

0.0698

0.0265	400

400

400	0.00064

0.001

0.00038	0.00087

0.0014

0.00051	0.00151

0.0024

0.00089	6,500

4,100

11,000

Lettuce (head)

Lettuce (leaf)

Spinach	0.7166

0.7040

0.0155	1,600

1,600

1,600	0.041

0.04

0.00088	0.056

0.055

0.0012	0.097

0.095

0.00208	100

100

4,700

Squash

Melon

Cucumber	0.00696

0.04572

0.0398	1,600

1,600

1,600	0.0004

0.0026

0.0023	0.00054

0.0036

0.0031	0.00094

0.0062

0.0054	10,000

1,600

1,800

Tomato

Pepper	0.0337

0.0742	160

1,600	0.00019

0.0042	0.00026

0.0058	0.00045

0.01	22,000

980

Cabbage 

& Broccoli

Mustard green	0.3775

0.0526	480

480	0.0065

0.0009	0.0088

0.0012	0.0153

0.0021	640

4,700

Barley 

Oats

Wheat 

Triticale, Rye Sorghum

Corn

Millet	0.00068	19,000

26,000

30,000

20,000

800

3,000

2,800	0.00046 

0.00063

0.00073

0.00049

0.000019

0.000073

0.000079	0.00063

0.00086

0.00099

0.00066

0.000026

0.000099

0.000092	0.00109

0.00149

0.00172

0.00115

0.000045

0.000172

0.000171	9,000

6,600

5,700

8,500

220,000

57,000

57,000

Potato seed pieces	0.00013	60,000	0.000279	0.000379	0.000658	15,000

a	Daily amounts planted values are based on exposure SAC Policy #15 or
the information provided by the Registrant through Registration
Division. 

b	Daily dermal dose (mg/kg/d) =  [unit dermal exposure (0.25 mg/lb ai)
× dermal absorption (0.01) × application rate (lb ai/lb seed) × daily
amounts treated /  body weight (70 kg).

c	Daily inhalation dose (mg/kg/d) = (unit exposure (0.00342 mg/lb ai) ×
application. rate (lb ai/lb seed) × daily amounts treated / body weight
(70 kg).

d	Combined daily dose (mg/kg/d) =  Daily dermal dose (mg/kg/d) + Daily
inhalation dose (mg/kg/d).

e	MOE = NOAEL (9.8 mg/kg/d) / combined daily dose.  UF = 100.			

10.0	Data Needs and Label Recommendations  TC \l1 "10.0	Data Needs and
Label Recommendations 

10.1	Toxicology  TC \l2 "10.1	Toxicology 

None.

10.2	Residue Chemistry  TC \l2 "10.2	Residue Chemistry 

	•	Information is required clarifying the proposed use rates for
potatoes and cereal grains on the label for the 56% WP formulation (see
Use Directions Section).

	•	The use direction for “Root Vegetables” should be corrected to
read “Root and Tuber Vegetables.” 

	•	The label should be amended to prohibit the use of treated seeds
for food, feed, or oil purposes, including the production of seed
sprouts.

	•	The final reports depicting the frozen storage stability of
clothianidin in spinach and tomatoes are required for evaluation by HED.
 Submission of this report should be a condition of registration.

	•	To support the submitted soybean field rotational crop trials, data
are required demonstrating the stability of the TZNG method in frozen
soybean commodities for up to 18 months.  Submission of these data
should be a condition of registration.

	•	A revised Section F is required incorporating the changes to the
proposed tolerances recommended by HED (see Table 10).

Although additional data are being requested, sufficient data are
available to support permanent tolerances on the requested commodities. 
HED recommends establishing permanent tolerances for residues of
clothianidin as detailed in Table 10.  The tolerance expression should
be revised to read as follows:

Tolerances are established for residues of the insecticide clothianidin,
including its metabolites and degradates, in or on the commodities in
the table below as a result of the application of clothianidin. 
Compliance with the tolerance levels specified below is to be determined
by measuring only clothianidin
[(E)-N-[(2-Chloro-5-thiazolyl)methyl]-N’-methyl-N”-nitroguanidine]
in or on the commodity.  

10.3	Occupational and Residential Exposure  TC \l2 "10.3	Occupational
and Residential Exposure 

	•	The label should be revised to require loader/applicators to wear a
dust-mist respirator.

	•	In order to mitigate risks of concern associated with uses on
lettuce and cabbage seed, the seed-treatment products should be packaged
in water-soluble packets.  Alternatively, applications rates may be
lowered by 3.2-fold for cabbage and 6-fold for lettuce.

Table 10. 	Tolerance Summary for Clothianidin

Commodity	Proposed Tolerance (ppm)	Recommended Tolerance (ppm) 1
Comments; 

Correct Commodity Definition

Vegetable, root, except sugar beet, Subgroup 1B	0.6	0.8	Adequate seed
treatment data are available on carrot and radish roots.

Vegetable, tuberous and corm, Subgroup 1C 	0.2	0.3	Adequate seed
treatment data are available on potato.  The recommended tolerance is in
accord with the current Canadian MRL.

Vegetable, leaves of root and tubers, Group 2	None	0.6	Adequate seed
treatment data are available on radish tops.

Vegetable, bulb, Group 3	0.2	0.45	Adequate data seed treatment data are
available on bulb and green onions.

Vegetable, bulb, Group 3-07

Vegetable, leafy greens, except Brassica, Subgroup 4A	1.1	0.7 2

(3.0)	Adequate seed treatment data are available on lettuce (head and
leaf), and spinach.

Vegetable, Brassica, leafy, Group 5	0.35	0.4 2

(1.9)	Adequate seed treatment data are available on broccoli, cabbage,
and mustard greens.

Vegetable, fruiting, Group 8	0.01	0.01 2

(0.20)	Adequate seed treatment data are available on tomatoes and
peppers.  Residues were <LOQ in/on all pepper and tomato samples.

Vegetable, cucurbit, Group 9	0.01	0.01 2

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The tolerance was calculated using the tolerance spreadsheet and the
wheat hay residue data.

Grain, cereal, forage, fodder and hay, Group 16, stover	None	0.1	The
tolerance is based on the existing field corn and sorghum field trial
data, and replaces separate tolerances on corn and sorghum stover.

Grain, cereal, forage, fodder and hay, Group 16, straw	None	0.05	The
tolerance was calculated using the tolerance spreadsheet and the wheat
straw residue data.

Potato, chips	None	0.6	Values are in accord with Canadian Maximum
Residue Limits (MRLs).

Potato, flakes	None	1.5

	1	Tolerances were calculated using the tolerance harmonization
spreadsheet unless otherwise indicated.

2	Higher tolerances (in parentheses) for these crop groups are being
recommended based a petition for foliar application uses (PP# 8F7395,
DP# 355373).

References:  TC \l1 "References: 

D355373.	Clothianidin: Human Health Risk Assessment for Proposed Uses on
Berries (Group 13-07H), Brassica Vegetables (Group 5), Cotton, Cucurbit
Vegetables (Group 9), Fig, Fruiting Vegetables (Group 8), Leafy Green
Vegetables (Group 4A), Peach, Pomegranate, Soybean, Tree Nuts (Group
14), and Tuberous and Corm Vegetables (Group 1C).  13 August 2009.

D357454.	Clothianidin; Petitions for Tolerances and Seed Treatment Uses
on Root and Tuber Vegetables, Bulb Vegetables, Leafy Greens, Brassica
Leafy Vegetables, Fruiting Vegetables, Cucurbit Vegetables, and Cereal
Grains (except rice).  Summary of Analytical Chemistry and Residue Data.
 5 August 2009.

D363338.	Clothianidin: Occupational and Residential Exposure/Risk
Assessment of Clothianidin for Section 3 Registration of New Seed
Treatment Uses on Vegetables, Cereal Grains and Potato. 16 July 2009.

D364363.	Clothianidin Acute and Chronic Aggregate Dietary (Food and
Drinking Water) Exposure and Risk Assessments.  11 August 2009.

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