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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF

CHEMICAL SAFETY AND

POLLUTION PREVENTION

MEMORANDUM

Date: 7-MAR-2013

SUBJECT: Imidacloprid. Section 3 Request for use on Oyster Beds in Washington (WA), 

and Section 18 Emergency Exemption Request for use on Sugarcane in Louisiana 

(LA). Human-Health Risk Assessment. 

PC Code: 129909 DP Barcodes: D399719 and D407172

Decision Nos.: 461091 and 472398 Registration No.: xxx-xxx, xxx-xxx, 264-758

Petition Nos.: 2E7988 and 12LA11 Regulatory Action: Section 3 Registration

Risk Assessment Type: Single Chemical Aggregate Case No.: 7605

TXR No.: NA CAS No.: 138261-41-3

MRID No.: NA 40 CFR: §180.472

FROM: Jennifer R. Tyler, Chemist

Chester E. Rodriguez, Ph.D., Toxicologist

Risk Assessment Branch 1 (RAB1)/Health Effects Division (HED; 7509P)

Matthew Crowley, Biologist

Chemistry and Exposure Branch (CEB)/HED (7509P)

THROUGH: George F. Kramer, Ph.D., Branch Senior Scientist

Dana M. Vogel, Deputy Division Director

RAB1/HED (7509P)

TO: Sidney Jackson/Barbara Madden

Tawanda Maignan/Debra Rate

Registration Division (RD; 7505P)

The HED of the Office of Pesticide Programs (OPP) is charged with estimating the risk to human 

health from exposure to pesticides. The RD of OPP has requested that HED evaluate hazard and 

exposure data and conduct dietary, occupational, residential and aggregate exposure assessments, 

as needed, to estimate the risk to human health that will result from the following: 1) the Section 

3 request for the use of the active ingredient (ai) imidacloprid (1-[(6-chloro-3-pyridinyl)methyl]-

N-nitro-2-imidazolidinimine) on oyster beds in Willapa Bay and Grays Harbor in WA; and 2) the 

Section 18 Emergency Exemption request for the use of imidacloprid on sugarcane in LA. A 

summary of the findings and an assessment of human-health risk resulting from the 

aforementioned uses are provided in this document. The risk assessment, residue chemistry data 

review, dietary exposure assessment, and occupational exposure assessment (sugarcane use) 

were provided by Jennifer Tyler (RAB1); the hazard characterization and endpoint selection by

Chester Rodriguez (RAB1); the occupational exposure assessment (oyster bed use) and 
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residential exposure assessment by Matthew Crowley (CEB); and the drinking water exposure 

assessment by José Melendez of the Environmental Fate and Effects Division (EFED).
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Table of Contents

1.0 Executive Summary............................................................................................................. 4

2.0 HED Recommendations....................................................................................................... 7

2.1 Data Deficiencies ............................................................................................................. 7

2.2 Tolerance Considerations................................................................................................. 7

2.3 Label Recommendations.................................................................................................. 8

3.0 Introduction.......................................................................................................................... 9

3.1 Chemical Identity ............................................................................................................. 9

3.2 Physical/Chemical Characteristics................................................................................... 9

3.3 Pesticide Use Pattern........................................................................................................ 9

3.4 Anticipated Exposure Pathways..................................................................................... 11

3.5 Consideration of Environmental Justice ........................................................................ 11

4.0 Hazard Characterization and Dose-Response Assessment................................................ 12

4.1 Mode of Action .............................................................................................................. 12

4.2 Toxicology Studies Available for Analysis ................................................................... 12

4.3 Absorption, Distribution, Metabolism, & Excretion (ADME) ...................................... 12

4.4 Dermal Absorption......................................................................................................... 12

4.5 Summary of Toxicological Effects ................................................................................ 12

4.6 SF for Infants and Children (FQPA SF) ........................................................................ 13

4.7 Toxicity Endpoint and Point of Departure Selections.................................................... 15

5.0 Dietary Exposure and Risk Assessment ............................................................................ 18

5.1 Residues of Concern Summary and Rationale............................................................... 18

5.2 Food Residue Profile...................................................................................................... 18

5.3 Water Residue Profile .................................................................................................... 19

5.4 Dietary Risk Assessment................................................................................................ 20

6.0 Residential (Non-Occupational) Exposure/Risk Characterization .................................... 21

6.1 Residential Handler Exposure and Risk Estimates........................................................ 22

6.2 Post-Application Exposure and Risk Estimates............................................................. 24

6.3 Combined Residential Risk Estimates (Multiple Exposure Scenarios)......................... 27

6.4 Residential Risk Estimates for Use in Aggregate Assessment ...................................... 28

6.5 Residential Bystander Post-application Inhalation Exposure ........................................ 30

6.6 Spray Drift...................................................................................................................... 30

7.0 Aggregate Exposure/Risk Characterization....................................................................... 30

7.1 Acute Aggregate Risk .................................................................................................... 31

7.2 Short-Term Aggregate Risk ........................................................................................... 31

7.3 Intermediate-Term Aggregate Risk................................................................................ 32

7.4 Chronic Aggregate Risk................................................................................................. 32

8.0 Cumulative Exposure/Risk Characterization..................................................................... 33

9.0 Occupational Exposure/Risk Characterization .................................................................. 33

9.1 Handler Exposure and Risk Estimates........................................................................... 33

9.2 Post-Application Exposure and Risk Estimates............................................................. 37

10.0 References.......................................................................................................................... 39

Appendix A. Toxicology Profile and Executive Summaries....................................................... 41

Appendix B. Physical/Chemical Properties................................................................................. 45
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1.0 Executive Summary

Background: Imidacloprid is an insecticide registered for uses on a variety of crops for the 

control of aphids, cucumber beetles, and whiteflies (including sweet potato or silverleaf 

whitefly). It is a member of the pyridylmethylamine class of compounds. Its mode of action

involves disruption of the nervous system by acting as an inhibitor at nicotinic acetylcholine 

receptors. Imidacloprid blocks the signals that are induced by acetylcholine at the post-synaptic 

membrane, resulting in normal nerve function impairment.

Imidacloprid is registered for use on several agricultural products, ornamental turf/plant 

products, seed treatments, pet care products, as well as structural pest products. Tolerances are 

currently established for the combined residues of imidacloprid and its metabolites containing 

the 6-chloropyridinyl moiety, all expressed as the parent, under 40 CFR §180.472 in/on various 

plant and livestock commodities. 

The Interregional Research Project No. 4 (IR-4) has submitted a petition (PP# 2E7988) for the 

use of imidacloprid on oyster beds to control burrowing shrimp. IR-4 has requested to add this 

use to the following labels: Protector®0.5G [a granular (G) product containing 0.5% 

imidacloprid as the active ingredient (ai); EPA Reg. No. xxx-xxx], and Protector®2F [a flowable 

concentrate (F) formulation containing 21.4% imidacloprid as the ai; EPA Reg. No. xxx-xxx]. In 

conjunction with this petition, tolerances have been requested for the combined residues of 

imidacloprid and its metabolites containing the 6-chloropyridinyl moiety, all expressed as the 

parent, in/on fish at 0.05 ppm, and fish-shellfish, mollusc at 0.05 ppm.

In addition, the Louisiana Department of Agriculture and Forestry (LDAF) has submitted a 

Section 18 Emergency Exemption request for the use of imidacloprid on sugarcane in LA. 

Hazard Assessment: The main targets of toxicity following oral administration of imidacloprid 

in mammalian systems were the nervous system and the thyroid. The most sensitive species 

tested was the rat. Evidence of neurotoxicity was reported in the rat acute neurotoxicity (ACN) 

study as changes in clinical signs and functional-observation battery (FOB) measurements, 

including decreased motor and locomotor activities, tremors, gait abnormalities, increased 

righting reflex impairments and body temperature, decreased number of rears and response to 

stimuli, and decreases in forelimb and hindlimb grip strength. Also, in a rat developmental 

neurotoxicity (DNT) study where imidacloprid was administered to pregnant/lactating dams in 

the diet, there were decreases in offspring motor activity measurements and a small but 

statistically significant decrease in the caudate/putamen width in the brain of female pups. No 

neurotoxic effects were reported in any other toxicity study including the rat subchronic 

neurotoxicity study.

Long-term dietary exposure to imidacloprid in a rat chronic toxicity study resulted in an 

increased incidence of mineralized particles in the thyroid colloid, and there were no effects 

reported in the rabbit dermal or rat inhalation studies. 

There was no evidence of increased qualitative or quantitative susceptibility in either rats or 

rabbits based on the results of prenatal developmental toxicity studies or a two-generation 

reproductive toxicity studies in rats. In the rat DNT study, however, the neurotoxic offspring 

effects noted above occurred in the presence of only maternal food consumption and body
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weight gain, indicating increased qualitative susceptibility in the young, though a clear noobserved-adverse-effect level (NOAEL) was established. 

There was no evidence of carcinogenic potential in either the rat chronic toxicity/carcinogenicity 

or mouse carcinogenicity studies, and imidacloprid was not genotoxic in a variety of assays. 

Food Quality Protection Act (FQPA) Decision: The RAB1 risk assessment team recommends 

that the FQPA Safety Factor (SF) be reduced to 1X for all exposure scenarios, except for the 

acute dietary endpoint for all populations for which the FQPA SF has been reduced to 3X 

because of the lack of NOAEL in the critical study selected (rat ACN). This decision was based 

on the following (see Section 4.6 for more detail):

The existing toxicology database for imidacloprid is adequate for FQPA SF evaluation. The 

following acceptable studies are available: developmental study in rats and rabbits; 2-generation 

reproduction study in rats; ACN and subchronic neurotoxicity (SCN) studies in rats; and DNT 

study in rats.

Evidence of neurotoxicity was observed in the ACN and DNT studies, but not the SCN study or 

any other studies in the imidacloprid database. 

There was increased qualitative susceptibility in the rat DNT study. However, the concern is low 

because a clear NOAEL was established for the offspring neurotoxic effects and the 

accompanying maternal food consumption and body weight decrements. Further, there was no 

evidence of increased susceptibility (quantitative or qualitative) based on the results of the prenatal developmental toxicity study in rats and rabbits and rat two-generation reproductive 

toxicity study. Therefore, there are no residual uncertainties for pre-/post-natal toxicity in this 

study.

There are no residual uncertainties in the exposure database.

Residue Chemistry and Drinking Water Assessments: The residue chemistry and drinking 

water databases are adequate to assess potential human exposure to imidacloprid. Adequate 

residue chemistry data have been submitted to support the proposed use on oyster beds as well as 

the proposed tolerances on fish and fish, shellfish-mollusc. No residue data have been submitted 

in support of the proposed Section 18 Emergency Exemption use on sugarcane. However, 

previously-submitted residue data are adequate to support the proposed use and time-limited 

tolerances on sugarcane, cane and sugarcane, molasses. EFED provided Tier 1 estimated 

drinking water concentrations (EDWCs) for surface water [using FQPA Index Reservoir 

Screening Tool (FIRST)] and groundwater [using Screening Concentration in Ground Water 

(SCI-GROW)] for imidacloprid and its degradates (imidacloprid urea, imidacloprid guanidine, 

and imidacloprid olefin).

Dietary (Food and Drinking Water) Exposure Assessment: Acute and chronic dietary (food 

and drinking water) exposure analyses were conducted for the general U.S. population and 

various population subgroups using the Dietary Exposure Evaluation Model software with the 

Food Commodity Intake Database (DEEM-FCID; Ver. 3.16). For acute and chronic dietary risk 

estimates, HED’s level of concern (LOC) is for estimates that exceed 100% acute populationadjusted dose (aPAD) or chronic population-adjusted dose (cPAD), respectively. The acute 

dietary exposure assessment was unrefined (assuming tolerance-level residues and assuming 

100% crop treated (CT) for all registered and proposed commodities), and the chronic dietary

exposure assessment was partially refined (using tolerance-level residues for all registered and 
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proposed commodities, and %CT information for some commodities). The results indicate that 

the acute (95th percentile) and chronic dietary exposure estimates are below HED’s LOC for the 

general U.S. population and all other population subgroups. For both acute and chronic 

assessments, the most highly exposed population subgroup is children 1-2 years old at 74% of 

the aPAD and 28% of the cPAD, respectively. 

Residential (Non-Occupational) Exposure Assessment: The proposed use of imidacloprid on 

oyster beds in WA can result in residential exposure via potential contact with residues in oysterbed water or sediment during recreational swimming. In addition, imidacloprid has several 

registered uses which may result in residential exposure. Based on these registered use patterns, 

there is a potential for short-term dermal and inhalation handler; and short-term dermal, 

inhalation, and incidental oral post-application exposure. There is also the potential for 

intermediate- and long-term exposures from the pet collar use, as it presents the potential for 

prolonged exposure via a continuous source and frequent contact (i.e., playing with pets). 

The equations and inputs for the post-application exposures due to the oyster bed use were 

generally developed from HED’s SWIMODEL V 3.0, and using updated body-weight 

information. All potential residential exposures from existing uses were re-evaluated utilizing 

the 2012 Residential standard operating procedures (SOPs) and policy changes on body weight. 

The resulting margins of exposure (MOEs) were all ≥140; and, therefore, do not exceed HED’s 

LOC.

Aggregate Exposure Scenarios and Risk Conclusions: For the proposed uses, human-health 

aggregate risk assessments have been conducted for the following exposure scenarios: acute 

aggregate exposure (food + drinking water), short-term aggregate exposure (food + drinking 

water + residential), and chronic aggregate exposure (food + drinking water + residential). 

Although there are intermediate-term residential exposures, an intermediate-term aggregate was 

not quantitatively assessed since (1) the short- and intermediate-term PODs are the same and (2) 

the short-term aggregate provides a worst-case estimate of residential exposure. For these 

reasons, the short-term aggregate is protective of the longer-term exposures. A cancer aggregate 

risk assessment was not performed because there is no evidence that imidacloprid is 

carcinogenic. All potential exposure pathways were assessed in the aggregate risk assessment as 

a conservative, health-protective measure. All aggregate risk estimates are not of concern to 

HED for the scenarios listed above. 

Occupational Handler and Post-application Exposure Estimates: Occupational short-term 

dermal and inhalation handler exposures are expected for individuals involved in applications of 

imidacloprid to oyster beds and sugarcane. For the proposed oyster bed use, HED has 

determined that risk estimates are not a concern (i.e., MOE >100) with baseline attire and 

chemical-resistant gloves (as required on the label). For the proposed sugarcane use, HED has 

determined that risks are not a concern with baseline attire. For aerial applications, no risks of 

concern were identified for individuals in enclosed cockpits.

For the proposed use of imidacloprid on oyster beds, the extent of post-application exposure is 

expected to be non-occupational in nature. Thus, any formal occupational post-application 

dermal or inhalation exposures (e.g., during oyster harvesting) is adequately covered in the 

residential exposure assessment. Based on the proposed Section 18 Emergency Exemption use 

of imidacloprid on sugarcane, occupational post-application dermal exposures are expected. The 
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short-term post-application assessments resulted in MOEs of 100 or greater on “day 0” 

(immediately after application) for all exposure activities, and are not of concern. The 12-hour 

restricted entry interval (REI) is adequate for the proposed use patterns.

Review of Human Research: 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 data, 

which include studies from Pesticide Handlers Exposure Database Version 1.1 (PHED 1.1); 

Agricultural Handler Exposure Task Force (AHETF) database; the Outdoor Residential 

Exposure Task Force (ORETF) database; and Agricultural Reentry Task Force (ARTF) database, 

are subject to ethics review pursuant to 40 CFR 26, have received that review, and are compliant 

with applicable ethics requirements. For certain studies that review may have included review 

by the Human Studies Review Board. Descriptions of data sources as well as guidance on their 

use can be found at http://www.epa.gov/pesticides/science/handler-exposure-data.html and 

http://www.epa.gov/pesticides/science/post-app-exposure-data.html.

2.0 HED Recommendations

HED concludes that the toxicological, residue chemistry and occupational/residential databases 

support a Section 3 registration and establishment of the tolerances listed in Section 2.2.2. In 

addition, the databases support a Section 18 Emergency Exemption request and the 

establishment of time-limited tolerances listed in Section 2.2.2. HED is not recommending for 

any additional data or label modifications in conjunction with this petition.

2.1 Data Deficiencies

No additional data are required to support the proposed use.

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

Adequate enforcement methods are available for determination of imidacloprid residues of 

concern in plant [Bayer gas chromatography/mass spectrometry (GC/MS) Method 00200] and 

livestock commodities (Bayer GC/MS Method 00191). These methods have undergone 

successful EPA petition method validations (PMVs), and the registrant has fulfilled the 

remaining requirements for additional raw data, method validation, independent laboratory

validation (ILV), and an acceptable confirmatory method [high-performance liquid 

chromatography/ultraviolet (HPLC/UV) Method 00357] (Memos, F. Griffith, 18-JUN-1993, 

D187911; 1-JUN-1994, D202113; 8-JUN-1994, D200233; 8-JUN-1995, D213252; and 18-DEC1995, D221591).

Bayer Corporation previously submitted adequate multiresidue (MRM) recovery data for 

imidacloprid and the metabolites 5-hydroxy imidacloprid, imidacloprid olefin, des nitro 

imidacloprid, and 6-chloronicotinic acid (6-CNA) through Food and Drug Administration (FDA) 

Protocols A through E (Memos, F. Griffith, 18-JUN-1993, D187911; 15-JUN-1993, D193027; 8-

JUN-1994, D200233; and 22-JUN-1994, D194206). Imidacloprid and its metabolites were not 

recoverable by these methods. The results of the MRM testing for imidacloprid were forwarded 
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to FDA for inclusion in the Pesticide Analytical Method Volume I (PAM I) (Memo, F. Griffith, 

15-JUL-1993, D193005).

2.2.2 Recommended Tolerances

Table 2.2.2. Tolerance Summary for Imidacloprid.

Commodity

Proposed 

Tolerance 

(ppm)

Currently 

Established 

Tolerance (ppm)

Recommended 

Tolerance (ppm)

Comments

(correct commodity definition)

2E7988 [§180.472(a) General]

fish 0.05 - 0.05

fish-shellfish, mollusc 0.05 - 0.05

12LA11 [§180.472(b) Section 18 emergency exemptions]

sugarcane, cane - - 6.0

sugarcane, molasses - - 50

2.2.3 Revisions to Petitioned-For Tolerances

PP# 2E7988: The residue chemistry data support the proposed tolerances for the combined 

residues of imidacloprid and its metabolites containing the 6-chloropyridinyl moiety, all 

expressed as the parent, in/on fish at 0.05 ppm, and fish-shellfish, mollusc at 0.05 ppm. No 

revisions to the proposed tolerances are necessary.

PP#12LA11: The residue chemistry data support the time-limited tolerances for the combined 

residues of imidacloprid and its metabolites containing the 6-chloropyridinyl moiety, all 

expressed as the parent, in/on sugarcane, cane at 6.0 ppm; and sugarcane, molasses at 50 ppm.

2.2.4 International Harmonization

There are currently no established Codex, Canadian, or Mexican maximum residue limits 

(MRLs) for imidacloprid on fish, molluscs, or sugarcane. Therefore, harmonization of MRLs 

and U.S. tolerances is not an issue at this time. 

2.3 Label Recommendations

HED is not recommending for any changes to the Protector®0.5G (EPA Reg. No. xxx-xxx), and 

Protector®2F (EPA Reg. No. xxx-xxx) labels.
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3.0 Introduction

3.1 Chemical Identity

Table 3.1. Test Compound Nomenclature.

Chemical Structure

Common Name Imidacloprid

Company Experimental Name Imidacloprid

IUPAC Name (EZ)-1-(6-chloro-3-pyridylmethyl)-N-nitroimidazolidin2-ylideneamine

CAS Name 1-[(6-chloro-3-pyridinyl)methyl]-N-nitro-2-

imidazolidinimine

CAS # 138261-41-3

End-use Products (EUP) Protector®

2F (EPA Reg. No. xxx-xxx)

Protector®0.5G (EPA Reg. No. xxx-xxx)

3.2 Physical/Chemical Characteristics

The physical and chemical properties, as well as a summary of relevant environmental fate 

parameters are detailed in Appendix B. Imidacloprid has a low vapor pressure (10-7 mPa); 

therefore, it is not a volatile pesticide. The low Henry's law constant (6.5X10-11 atm m3/mole) 

also indicates that it has a low potential of volatizing from water. Imidacloprid has a low octanol 

water partition coefficient (0.57); therefore, it is not expected to bioaccumulate in lipophilic 

matrices. It is highly soluble in water (1.54 g/L), which, coupled with its low octanol water 

coefficient, suggests a potential to leach to ground water, as well as transport to surface water via 

runoff. In view of its environmental fate properties including persistence for many months in 

soil and water, imidacloprid, will translocate throughout treated plants regardless of the method 

of application. 

3.3 Pesticide Use Pattern

PP#2E7988: The petitioner has submitted draft labels for the Protector®0.5G (EPA Reg. No. 

xxx-xxx), and Protector®2F (EPA Reg. No. xxx-xxx). A summary of the proposed use patterns 

are detailed in Table 3.3.1. The proposed imidacloprid labels direct mixers, loaders, applicators 

and other handlers to wear a long-sleeved shirt, long pants, shoes plus socks and chemicalresistant gloves. In addition, the label for the granule formulation directs users to wear a dust 

mask. The proposed label specifies a 12-hour REI.

N

N

N

Cl

C

H2

N

O2N

H
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Table 3.3.1. Summary of Proposed Directions for Use of Imidacloprid on Oyster Beds.

Use 

Site

Trade 

Name 

(EPA Reg. 

No.)

Application Equipment

App. 

Rate

(lb 

ai/A)

Max. 

Seasonal 

App. 

Rate

(lb ai/A)

PHI1

(days)

Max. 

# 

App.

Min.

GPA2

RTI3

(days)

Oyster 

beds

Protector®

0.5G 

(xxxxx-xx)

Drop/rotary spreader; 

Tractor-drawn 

spreader; Belly grinder

Helicopter

0.5 0.5 30 1 NA

NA

Protector®

2F

(xxxxx-xx)

Groundboom, 

Helicopter, Backpack 0.5 0.5 30 1

ground: 5

air: 2

Restrictions:

 Not for sale to any persons other than a member of the Willapa-Greys Harbor Oyster Growers Association.

 A single application/year is allowed.

 No adjuvants or surfactants allowed.

 Aerial applications must be made on beds exposed at low tide.

 Applications from a floating platform or boat may be made under water using a calibrated granular applicator.

 All application must be made between April 15 and December 15. Do not apply aerially during Federal Holidays.

 During aerial applications, all public access areas and public boat launches within 1⁄4 mile radius of bed shall be 

posted.

1. PHI = pre-harvest interval.

2. GPA = gallons of water per acre.

3. RTI = retreatment interval.

PP#12LA11: LDAF has submitted proposed use directions for the use of imidacloprid on 

sugarcane in LA. A maximum of 20,000 A can be treated under the requested Crisis Exemption. 

A summary of the proposed use patterns are detailed in Table 3.3.2. The proposed imidacloprid 

product labels direct mixers, loaders, applicators and other handlers to wear a long-sleeved shirt, 

long pants, shoes plus socks and chemical-resistant gloves. In addition, the label for the granule 

formulation directs users to wear a dust mask. The proposed label specifies a 12-hour REI.

Table 3.3.2. Summary of Proposed Directions for Use of Imidacloprid on Sugarcane in LA.

Use Site

Trade 

Name (EPA 

Reg. No.)

Application 

Equipment

App. 

Rate

(lb ai/A)

Max. 

Seasonal 

App. Rate

(lb ai/A)

Minimum

PHI1

(days)

Max. # 

App.

Min.

GPA2

RTI3

(days)

Sugarcane Admire®

Pro 

(264-758) Aerially 0.06-0.08 0.16 36 2 NS NS

1. PHI = pre-harvest interval. The minimum PHI was provided in an email dated 11/19/12 (personal communication between B. Simoneaux

to T. Maignan).

2. GPA = gallons of water per acre.

3. RTI = retreatment interval.

HED Conclusions: The use directions provided by the petitioner are adequate to allow 

evaluation of the residue data relative to the proposed Section 3 use of imidacloprid on oyster 

beds to control ghost shrimp, and the proposed Section 18 Emergency Exemption request for the 

use of imidacloprid on sugarcane in LA.
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3.4 Anticipated Exposure Pathways

RD has requested an assessment of human-health risk to support the proposed new use of 

imidacloprid 1) on oyster beds of Willapa Bay and Grays Harbor in Washington State to control 

burrowing shrimp, and 2) on sugarcane in LA. Humans may be exposed to imidacloprid in food 

and drinking water since imidacloprid may be applied directly to growing crops and oyster beds, 

and applications may result in imidacloprid reaching surface and ground water sources of 

drinking water. There are numerous registered residential uses of imidacloprid; therefore, human 

exposure in residential or non-occupational settings may occur. In an occupational setting, 

applicators may be exposed while handling the pesticide prior to application, as well as during 

application to oyster beds and sugarcane. In addition, for the proposed use on sugarcane, there is 

a possibility of post-application dermal exposure to occupational workers when reentering field 

previously treated with imidacloprid.

The most recent human-health risk assessment for imidacloprid was conducted in 2009 (Memo, 

G. Kramer et al., 16-MAR-2009; D375406). A human-health Scoping Document in support of 

Registration Review was also recently conducted (Memo, J. Tyler, 3-DEC-2008; D353984). 

This risk assessment considers all of the aforementioned exposure pathways based on the 

proposed new use of imidacloprid, but also considers the existing uses as well, particularly for 

the dietary and residential exposure assessments. 

3.5 Consideration of Environmental Justice

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 U.S. Department of 

Agriculture’s National Health and Nutrition Examination Survey, What We Eat in America 

(NHANES/WWEIA) 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 post-application 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.
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4.0 Hazard Characterization and Dose-Response Assessment

4.1 Mode of Action

Imidacloprid is a systemic insecticide effective against the larval, nymphal, and adult insect 

stages. Its postulated insecticidal mode of action involves inhibition at nicotinic acetylcholine 

receptors, resulting in nerve function impairment. Some of the toxic effects reported in 

mammals are also consistent with a neurotoxic mode of action.

4.2 Toxicology Studies Available for Analysis

The toxicological database for imidacloprid is adequate for characterization of its hazard, 

toxicity endpoint selection, and FQPA consideration. In the most recent risk assessment (Memo, 

G. Kramer et al., 16-MAR-2009; D375406), the only toxicity data gap noted was an 

immunotoxicity study as part of the revised 40 CFR §158 data requirements. Since then, a 

guideline 28-day rat immunotoxicity study has been submitted and reviewed by the Agency. 

The results of the study are included in this hazard characterization.

4.3 Absorption, Distribution, Metabolism, & Excretion (ADME)

Following oral administration in the rat, 14C-methylene-radiolabeled imidacloprid was rapidly

absorbed with a time to maximum plasma concentration of 1.1 - 2.5 hours post-dose. Absorption 

was also extensive based on the extent of urinary (70-80% of recovered radioactivity) and biliary

(~31.8% based on studies with bile-fistulated animals) excretion of radioactivity. Plasma 

elimination was biphasic with an estimated primary plasma clearance half-life of 3 hours and a 

secondary, minor half-life ranging between 26-118 hours. Urine was the primary route of 

excretion. Total tissue burden after 48 hours was approximately 0.5% of the administered 

radioactivity. Though retention of radioactivity was minimal, liver, kidney, lung, skin, and 

plasma showed the highest levels. Other less significant sites of radioactivity were the brain and 

testes. There were two major routes of biotransformation for imidacloprid. The first included an 

oxidative cleavage of the parent compound followed by dechlorination to give 6-CNA. The 

second route included the hydroxylation of imidazolidine. There were no significant differences 

in ADME processes between sexes or dose levels tested.

4.4 Dermal Absorption

There is no dermal absorption study available for imidacloprid. However, a dermal-absorption 

factor (DAF) of 7.2% has been previously estimated based on the ratio of the maternal lowestobserved-adverse-effect level (LOAEL) of 72 mg/kg bw/day from a rabbit developmental 

toxicity study and the NOAEL from a dermal-specific toxicity study in rabbits.

4.5 Summary of Toxicological Effects

The main targets of toxicity following oral administration of imidacloprid in mammalian systems 

were the nervous system and the thyroid. The most sensitive species tested was the rat. 

Evidence of neurotoxicity was reported in the rat ACN as changes in clinical signs and FOB 

measurements including decreased motor and locomotor activities, tremors, gait abnormalities, 

increased righting reflex impairments and body temperature, decreased number of rears and 
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response to stimuli, and decreases in forelimb and hindlimb grip strength. Also, in a rat DNT 

study where imidacloprid was administered to pregnant/lactating dams in the diet, there were 

decreases in offspring motor activity measurements and a small but statistically significant 

decrease in the caudate/putamen width in the brain of female pups. No neurotoxic effects were 

reported in any other toxicity study including the rat subchronic neurotoxicity study.

Long-term exposure to imidacloprid resulted in an increased incidence of mineralized particles in 

the thyroid colloid of rats, body weight decrements in mice, and no toxic effects in dogs. No 

other thyroid effects were measured in the rat study.

In prenatal developmental toxicity studies in rats and rabbits, there were developmental effects at 

dose levels that also produced maternal toxicity. In the rat study, there was a slight increase in 

the incidence of wavy ribs at a dose level higher than that causing deficit in maternal bodyweight gain. Developmental effects in the rabbit occurred at the same dose as severe maternal 

toxicity including deaths and body-weight deficits. Developmental effects in rabbits included 

abortions, total litter resorptions, increased post-implantation loss due to increased late 

resorptions, decreased fetal weights, and an increased incidence of wavy ribs in the high-dose 

group. In the rat two-generation reproductive toxicity study, there were decreases in pup body

weights reported in both litters of each generation at the same dose level as parental effects 

manifested as decreased premating and gestational body-weight gain.

In a recently submitted immunotoxicity study in rats, there were no immunotoxic effects reported 

at the highest dose level tested. The only treatment-related effects were limited to deficits in 

body weights and food consumption at the highest dose tested.

No toxic effects were identified at the limit dose of 1000 mg/kg bw/day in a dermal toxicity

study in rabbits.

In a rat 4-week inhalation toxicity study, there were no effects reported (either portal of entry or 

systemic) at the highest concentration tested.

There was no evidence of carcinogenic potential in either the rat chronic toxicity/carcinogenicity 

or mouse carcinogenicity studies. The RfD/Peer Review Committee classified imidacloprid as a 

Group E chemical, “Evidence of non-carcinogenicity for humans,” by all routes of exposure 

based upon lack of evidence of carcinogenicity in rats and mice (11/10/1993). There was also no 

concern for mutagenicity across a host of genotoxicity assays.

4.6 SF for Infants and Children (FQPA SF)

The RAB1 risk assessment team recommends that the FQPA SF be reduced to 1X for all 

exposure scenarios, except for the acute dietary endpoint for all populations for which the FQPA 

SF has been reduced to 3X because of the lack of a NOAEL in the critical study (the rat ACN). 

The rationale is provided below.
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4.6.1 Completeness of the Toxicology Database

The existing toxicology database for imidacloprid is complete and adequate for FQPA SF 

evaluation. The following studies are available for consideration: developmental toxicity

studies in rats and rabbits; two-generation reproductive toxicity study in rats; ACN and SCN

studies in rats, and DNT study in rats.

4.6.2 Evidence of Neurotoxicity

The neurotoxic potential of imidacloprid has been addressed given its postulated insecticidal 

neurotoxic mode of action, involving nerve function impairment through inhibition at nicotinic 

acetylcholine receptors. Evidence of neurotoxicity was observed in the ACN and DNT studies 

but not the SCN study as previously described in the toxicological effects section of this 

document. No signs of effects on the nervous system were reported in any other studies in the 

imidacloprid database. 

4.6.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal

There is no evidence of increased susceptibility (quantitative or qualitative) based on the results 

of pre-natal developmental toxicity studies in rats and rabbits and the rat two-generation 

reproductive toxicity study where developmental effects were observed at the same or higher 

doses than those causing maternal effects. In the rat DNT study, however, there is evidence of 

increased qualitative susceptibility, but the concern is low since: 1) the effects in pups (bodyweight deficits, decreased motor activity, and small decrease in female caudate/putamen width) 

are well-characterized with a clear maternal NOAEL; 2) the pup effects occurred at the same 

dose as maternal toxicity (decreased body-weight gain and food consumption); and 3) the doses 

and endpoints selected for regulatory purposes are protective of the pup effects noted at higher 

doses in the DNT study. Therefore, there are no residual uncertainties for pre-/post-natal toxicity

in this study.

4.6.4 Residual Uncertainty in the Exposure Database

The acute dietary food exposure assessment utilizes existing and proposed tolerance-level 

residues and 100% CT information for all commodities. By using these screening-level 

assessments, actual exposures/risks will not be underestimated.

The chronic dietary food exposure assessment utilizes existing and proposed tolerance-level 

residues and % CT data verified by the Biological and Economics Analysis Division (BEAD) for 

several existing uses. For all proposed uses, 100% CT is assumed. The chronic assessment is 

somewhat refined and based on reliable data and will not underestimate exposure/risk.

The dietary drinking water assessment utilizes water concentration values generated by models 

and associated modeling parameters, which are designed to provide conservative, healthprotective, high-end estimates of water concentrations which will not likely be exceeded.

The residential handler and post-application exposure assessments are based upon the residential 

SOPs in conjunction with PHED unit exposures. The residential SOPs are based upon 

reasonable worst-case assumptions and are not expected to underestimate risk. These 
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assessments of exposure are not likely to underestimate the resulting estimates of risk from 

exposure to imidacloprid.

4.7 Toxicity Endpoint and Point of Departure Selections

4.7.1 Dose-Response Assessment

Table 4.7.4 summarizes the toxicological doses and endpoints selected for human-health risk 

assessment. 

Acute Dietary Endpoint (all populations): The acute endpoint for all populations (including 

females of childbearing age) was based on decreased motor and locomotor activity in females in 

the rat acute neurotoxicity study at the LOAEL of 42 mg/kg/day. An FQPA SF of 3X was 

retained in the form of a database uncertainty factor (UF) for lack of a NOAEL. The database 

UF of 3X was judged as adequate (as opposed to 10X) because the effect (decreased motor and 

locomotor activity) shows a good dose response with minimal change as compared to the control 

group at the LOAEL of 42 mg/kg/day, and statistical significance was only achieved at the next 

higher dose of 151 mg/kg/day. Furthermore, the LOAEL of 42 mg/kg/day is comparable to the 

LOAEL of 55 mg/kg/day for offspring effects (which includes decreased motor activity) in the 

rat DNT study, and the extrapolated NOAEL of 14 mg/kg/day (42/3 = 14) is comparable to and 

more protective than the NOAEL of 20 mg/kg/day established in the DNT for offspring effects.

The standard combined UF of 100X is being applied to account for interspecies (10X) and 

intraspecies (10X) extrapolation. Thus, the acute reference dose (aRfD) and aPAD are 

equivalent at 0.14 mg/kg/day since the FQPA SF is in the form of a database uncertainty (lack of 

NOAEL) rather than increased susceptibility in the young.

Chronic Dietary (all populations): This endpoint was based on the increased incidence of 

mineralized particles in thyroid colloids in male rats at the LOAEL of 16.9 mg/kg/day (NOAEL 

= 5.7 mg/kg/day) in a combined chronic toxicity/carcinogenicity rat study. The standard 

combined UF of 100X was applied to account for interspecies (10X) and intraspecies (10X) 

extrapolation. The FQPA SF was not retained for this exposure scenario since the toxicology

database is adequate and there were no residual uncertainties for pre-and or post-natal 

susceptibility. Thus, the chronic reference dose (cRfD) and cPAD are equivalent at 0.057

mg/kg/day.

Incidental Oral [short (1-30 days) - and intermediate (1-6 months)-term]: This endpoint was 

based on decreased maternal body-weight gain observed in the rat prenatal developmental 

toxicity study at the LOAEL of 30 mg/kg/day (NOAEL = 10 mg/kg/day). The NOAEL of 30 

mg/kg/day is comparable to the extrapolated NOAEL of 14 mg/kg/day from the rat ACN study

also evaluated for this endpoint. An MOE of 100 based on interspecies (10X) and intraspecies 

(10X) extrapolation is adequate for this scenario. 

Incidental Oral [long-term (>6 months)]: This endpoint was based on the increased incidence of 

mineralized particles in thyroid colloids in male rats at the LOAEL of 16.9 mg/kg/day (NOAEL 

= 5.7 mg/kg/day) in a combined chronic toxicity/carcinogenicity rat study. The standard 

combined UF of 100x was applied to account for interspecies (10X) and intraspecies (10X) 

extrapolation. The FQPA SF was not retained for this exposure scenario since the toxicology
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database is complete and there were no residual uncertainties for pre-and or post-natal 

susceptibility.

Dermal [short (1-30 days) - and intermediate (1-6 months)-term]: This endpoint was based on 

decreased maternal body-weight gain observed in the rat prenatal developmental toxicity study at 

the LOAEL of 30 mg/kg/day (NOAEL = 10 mg/kg/day). This point of departure (POD) is 

higher than the LOAEL of 100 mg/kg/day (NOAEL = 30 mg/kg/day) for developmental effects 

based on an increase incidence of wavy ribs. Although a 21-day rabbit dermal toxicity study was 

performed and no toxic effects were observed, such studies are based on non-pregnant adult 

animals and do not account for potential developmental effects.

A DAF of 7.2% has been previously estimated based on the ratio of the LOAEL of 72 mg/kg/day

from a rabbit developmental toxicity study and the NOAEL of 1000 mg/kg/day from a dermalspecific toxicity study in rabbits. An MOE of 100 based on interspecies (10X) and intraspecies 

(10X) extrapolation is adequate for this scenario. 

Dermal [long (>6 months)-term]: Because of the duration of this exposure scenario, this 

endpoint was based on the chronic toxicity/carcinogenicity study in rats. As noted above, the 

effects consisted of an increased incidence of mineralized particles in thyroid colloids (postulated 

reservoirs in the thyroid gland for production and storage of thyroid hormones) in male rats at the 

LOAEL of 16.9 mg/kg/day (NOAEL = 5.7 mg/kg/day). A DAF of 7.2% was previously 

estimated for imidacloprid (Memo, G. Kramer et al., 16-MAR-2009; D375406) yielding a 

dermal-equivalent dose (DED) of ≈ 81 mg/kg/day. An MOE of 100 which includes interspecies 

(10X) and intraspecies (10X) extrapolation is adequate for this scenario.

Inhalation [short (1-30 days) - and intermediate (1-6 months)-term]: This endpoint was based 

on decreased maternal body-weight gain observed in the rat prenatal developmental toxicity

study at the LOAEL of 30 mg/kg/day (NOAEL = 10 mg/kg/day). This POD is higher than the

offspring LOAEL of 100 mg/kg/day (NOAEL = 30 mg/kg/day) based on an increase incidence 

of wavy ribs. Although a 4-week rat inhalation toxicity study was performed and no toxic 

effects were observed (no LOAEL identified), such studies are based on non-pregnant adult 

animals and do not account for potential developmental effects. 100% absorption is being 

assumed via this route of exposure. An MOE of 100 based on interspecies (10X) and 

intraspecies (10X) extrapolation is adequate for this scenario.

Inhalation [long (>6 months)-term]: Because of the duration of this exposure scenario, this 

endpoint was based on the chronic toxicity/carcinogenicity study in rats. As noted above, the 

effects consisted of an increased incidence of mineralized particles in thyroid colloids (postulated 

reservoirs in the thyroid gland for production and storage of thyroid hormones) in male rats at the 

LOAEL of 16.9 mg/kg/day (NOAEL = 5.7 mg/kg/day). An MOE of 100 which includes 

interspecies (10X) and intraspecies (10X) extrapolation is adequate for this scenario.

4.7.2 Recommendation for Combining Routes of Exposure for Risk Assessment

When there are potential occupational and residential exposures to a pesticide, the risk 

assessment must address exposures from three major sources, oral, dermal and inhalation, and 

determine whether the individual exposures can be combined if they have the same toxicological 

effects. For short- and intermediate-exposure, dermal and inhalation exposures can be combined 
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because the same endpoint (maternal body weight gain deficits) is being used. Similarly, for 

long-term exposures, oral, dermal and inhalation endpoints can be combined because of the use 

of the same endpoint (thyroid toxicity) from the rat chronic toxicity study.

4.7.3 Cancer Classification

Imidacloprid has been classified as a Group E chemical, “Evidence of non-carcinogenicity for 

humans,” by the HED RfD/Peer Review Committee (11/10/93).

4.7.4 Summary of Points of Departure and Toxicity Endpoints Used In Human-Health 

Risk Assessment

Table 4.7.4. Imidacloprid: Summary of Toxicological Endpoints and Points of Departure for Residential Human-Health 

Risk Assessment.

Exposure

Scenario

Dose Used in Risk 

Assessment, SFs

RfD, LOC for Risk 

Assessment Study and Toxicological Effects

Acute Dietary

(all populations)

LOAEL = 42 mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 3X

aRfD = aPAD = 0.14 

mg/kg

Acute neurotoxicity – rat

LOAEL = 42 mg/kg/day, based upon the 

decrease in motor and locomotor activities 

observed in females.

Chronic Dietary

(All populations)

NOAEL = 5.7 mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 1X

cRfD = cPAD = 0.057 

mg/kg/day

Combined chronic toxicity/carcinogenicity – rat

LOAEL = 16.9 mg/kg/day, based upon 

increased incidence of mineralized particles in 

thyroid colloid in males.

Incidental Oral

[Short- (1-30 days) & 

Intermediate (1-6

months) terms]

NOAEL = 10 mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 1X

LOC for MOE = 100 

Prenatal developmental toxicity – rat

LOAEL = 30 mg/kg/day based on decreased 

maternal body weight gain.

Incidental Oral

[Long-Term (> 6 

months)]

NOAEL = 5.7 mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 1X

LOC for MOE = 100

Combined chronic toxicity/carcinogenicity – rat

LOAEL = 16.9 mg/kg/day, based upon 

increased incidence of mineralized particles in 

thyroid colloid in males.

Dermal

[Short- (1-30 days) & 

Intermediate (1-6 

months) terms]

NOAEL = 10 mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 1X

DAF = 7.2%

LOC for MOE = 100 

Prenatal developmental toxicity – rat

LOAEL = 30 mg/kg/day based on decreased 

maternal body weight gain 

Dermal

[Long-Term (> 6 

months)]

NOAEL = 5.7 mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 1X

(DAF = 7.2%)

LOC for MOE = 100 

Combined chronic toxicity/carcinogenicity – rat

LOAEL = 16.9 mg/kg/day, based upon 

increased incidence of mineralized particles in 

thyroid colloid in males.

Inhalation

[Short- (1-30 days) & 

Intermediate (1-6 

months) terms]

NOAEL = 10 mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 1X

(Assumed 100% absorption)

LOC for MOE = 100 

Prenatal developmental toxicity – rat

LOAEL = 30 mg/kg/day based on decreased 

maternal body weight gain

Long-Term Inhalation

(>6 months)

NOAEL = 5.7 mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 1X

(Assumed 100% absorption)

LOC for MOE = 100 

Combined chronic toxicity/carcinogenicity – rat

LOAEL = 16.9 mg/kg/day, based upon 

increased incidence of mineralized particles in 

thyroid colloid in males.
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Table 4.7.4. Imidacloprid: Summary of Toxicological Endpoints and Points of Departure for Residential Human-Health 

Risk Assessment.

Exposure

Scenario

Dose Used in Risk 

Assessment, SFs

RfD, LOC for Risk 

Assessment Study and Toxicological Effects

Cancer

(oral, dermal, 

inhalation)

Classified as Group E, “Evidence of non-carcinogenicity for 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). FQPA SF = FQPA Safety Factor. PAD = populationadjusted dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of exposure. LOC = level of concern. 

5.0 Dietary Exposure and Risk Assessment

The residue chemistry data submitted in support of the proposed Section 3 use on oyster beds 

were reviewed by HED in a memo dated 7-MAR-2012 (Memo, J. Tyler; D400189). The 

EDWCs were provided by EFED (Memo, J. Melendez; 22-JULY-2009). The acute and chronic 

dietary exposure assessment was completed in a HED memorandum dated 7-MAR-2012 (Memo, 

J. Tyler; D400187).

5.1 Residues of Concern Summary and Rationale

Data concerning the metabolism of imidacloprid in apples, potatoes, tomatoes, eggplant, 

cottonseed, field corn, tobacco, ruminants, and poultry have been submitted and reviewed 

(Memos, F. Griffith, 20-SEP-1993, D185148; 8-JUN-1994, D200233; and 29-FEB-1996, 

D217632). The results of the aforementioned plant and livestock metabolism studies were 

presented to the HED Metabolism Assessment Review Committee (MARC) in 1993 (Memo, F. 

Griffith, 25-JUN-1993, TXR#: 0050886). The nature of imidacloprid residues in plants and 

livestock is adequately understood. The residue of concern in plants and livestock is 

imidacloprid and its metabolites containing the 6-chloropyridinyl moiety, all expressed as the 

parent, as specified in 40 CFR §180.472. In a meeting on 18-DEC-2002, the HED MARC 

recommended that for surface water risk assessment, degradates of concern should be parent and 

the three degradates: imidacloprid urea, imidacloprid guanidine, and imidacloprid olefin (Memo, 

J. Tyler, 13-JAN-2003; D287400).

5.2 Food Residue Profile

PP# 2E7988: No magnitude of the residue in fish or nature of the residue in fish studies were 

submitted in support of the proposed use on oyster beds. However, the registrant recently 

submitted a waiver request for both studies. The request was presented to the HED Science 

Advisory Council for Chemistry (ChemSAC) on 23-FEB-2011, and the ChemSAC agreed with 

the rationale for the waiver (ChemSAC Minutes). Therefore, data demonstrating the magnitude 

of the residue or nature of the residue in fish are not necessary to support the proposed use on 

oyster beds. The ChemSAC determined that the proposed tolerance for residues of imidacloprid 

and its metabolites containing the 6-chloropyridinyl moiety, all expressed as the parent, in/on 

fish at 0.05 ppm is appropriate.

The submitted magnitude of the residue study in oysters was conducted in accordance with 

OPPTS Guideline 860.1400, and the data are adequate to support the proposed use. Total 
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residues of imidacloprid were less than limit of quantitation [LOQ, defined as the lowest level of 

method validation, LLMV (0.05 ppm)] in/on oyster meat harvested 26-86 days following either a 

single application of Mallot®0.5G at an application rate of 0.50 lb ai/A; or Mallot 2F®at an 

application rate of 2.0 lb ai/A. Samples were analyzed for total imidacloprid residues using an 

acceptable method, and the study is supported by adequate storage stability data. For oysters, the 

Organization for Economic Co-operation and Development (OECD) tolerance-calculation 

procedures could not be used to calculate a possible tolerance as residues of imidacloprid were 

<LOQ in/on all samples of oyster meat. Therefore, the tolerance of 0.05 ppm for fish-shellfish, 

mollusc is appropriate.

PP#12LA11: No residue chemistry data were submitted in support of the proposed Section 18 

Emergency Exemption request for the use of imidacloprid on sugarcane in LA. In connection 

with this Section 18, time-limited tolerances should be established at 6.0 ppm in or on sugarcane, 

cane and at 50 ppm for sugarcane, molasses.

The recommended tolerance level of 6.0 ppm for sugarcane, cane is based on the established 

tolerance level for leaf petioles, subgroup 4B (Memo, Y. Donovan, 23-MAR-1999; D242320). 

According to current imidacloprid labels, soil-directed application may be made to leaf petioles, 

subgroup 4B at a maximum application rate of 0.38 lb ai/A, and a minimum PHI of 45 days. The 

results of previously submitted celery crop field trial study indicate that the highest residue level 

of imidacloprid on treated celery is 5.62 ppm following a single soil sidedress application at a 

rate of 0.5 lb ai/A.

In addition, the results of a previously submitted sugarbeet processing study indicate that total 

residues of imidacloprid do not concentrate in sugar (0.025X), but do concentrate in molasses 

(8.3X) (Memo, F. Griffith, 16-MAY-1995; D212683). Therefore, a tolerance of 50 ppm (6.0-

ppm tolerance x 8.3) is necessary for sugarcane, molasses. A separate tolerance for sugar is not 

needed; however, a reduction factor of 0.025X was applied to sugarcane, sugar (6.0 ppm x 0.025 

= 0.15 ppm) in the acute and chronic dietary exposure assessment.

5.3 Water Residue Profile

EFED provided Tier 1 EDWCs for surface water (using FIRST) and groundwater (using SCIGROW) for imidacloprid and its degradates (imidacloprid urea, imidacloprid guanidine, and 

imidacloprid olefin). EDWCs were not provided for the proposed oyster bed use as EFED does 

not expect any impacts on drinking water from this particular use (personal communication 

between M. Barrett and C. Smith, 1-NOV-2012). Therefore, the EDWCs provided in 2009 were 

incorporated used in this risk assessment. The EDWCs in the 2009 memo were calculated based 

on a maximum application rate of 0.5 lb ai/A/season. The acute and chronic EDWCs in surface 

water are 36.0 ppb and 17.2 ppb of imidacloprid, based on applications of the chemical to citrus. 

The SCI-GROW generated groundwater EDWC is 2.09 ppb of imidacloprid. 

Table 5.3. Estimated Tier 1 EDWCs of Imidacloprid in Drinking Water.

Drinking Water Source (Model Used) Use (Rate modeled) EDWC (ppb)

Groundwater (SCI-GROW)

Citrus (0.5 lb ai/A)

Acute and Chronic 2.09

Surface water (FIRST Acute 36.0

Chronic 17.2
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5.4 Dietary Risk Assessment

Acute and chronic aggregate dietary (food and drinking water) exposure and risk assessments 

were conducted using the DEEM-FCID (Ver. 3.16), which uses food consumption data from the 

USDA’s NHANES/WWEIA. This dietary survey was conducted from 2003 to 2008. 

5.4.1 Description of Residue and Percent Crop Treated Data Used in Dietary Assessment

The acute dietary exposure assessment was unrefined, using tolerance-level residues and 

assuming 100% CT for all registered and proposed commodities. The chronic dietary exposure 

assessment was partially refined using tolerance-level residues for all registered and proposed 

commodities, and % CT information for some commodities. Exposure to drinking water was 

incorporated directly in the acute and chronic dietary assessments using the acute (peak) and 

chronic (annual average) concentrations for surface water generated by the FIRST model, 

respectively.

In a memo dated 2-AUG-2012, the BEAD provided updated estimated % CT information for 

several commodities (Memo, J. Alsadek, D403995). For the chronic assessment, the following 

average weighted % CT information was used: almonds: <1%; apples: 30%; artichokes: 5%; 

avocados: <1%; beans, green: 5%; blueberries: 10%; broccoli: 55%; cabbage: 25%; caneberries: 

10%; cantaloupe: 40%; carrots: <1%; cauliflower: 50%; celery: 10%; cherries: 15%; corn (seed 

treatment): <2.5%; cotton: 5%; cotton (seed treatment): 5%; cucumbers: 5%; dry beans/peas: 

<1%; eggplant: 60%; filberts (hazelnuts): <2.5%; grapefruit: 25%; grapes: 30%; honeydew: 

30%; lemons: 5%; lettuce: 65%; onions: <1%; oranges: 20%; peaches: 5%; peanuts: <1%; pears: 

5%; peas, green: <2.5%; pecans: 15%; peppers: 15%; pistachios: <1%; potatoes: 35%; prunes: 

<1%; pumpkin: 10%; sorghum (seed treatment): 15%; soybeans (seed treatment): 5%; spinach: 

20%; squash: 15%; strawberries: 10%; sugar beets: <2.5%; sweet corn: <1%; tangerines: 10%; 

tobacco: 25%; tomatoes: 25%; walnuts: 5%; watermelon: 20%; wheat (seed treatment): 10%.

5.4.2 Acute Dietary Risk Assessment

An unrefined (using tolerance-level residues and assuming 100% CT for all registered and 

proposed commodities) acute dietary exposure assessment was conducted for the general U.S.

population and various population subgroups. This assessment indicates that the acute dietary

exposure estimates are below HED’s LOC, <100% aPAD, at the 95th exposure percentile for the 

general U.S. population and all other population subgroups. The acute dietary exposure is 

estimated for the U.S. population at 28% of the aPAD and the most highly exposed population 

subgroup, children 1-2 years old, at 74% of the aPAD. The acute assessment was highly

conservative, using several upper-end assumptions. Additional refinements, such as inclusion of 

anticipated residues (ARs) and %CT data could be made in order to refine the acute assessment. 

However, HED is confident that the assessment does not underestimate risk to the general U.S. 

population or any population subgroup.

5.4.3 Chronic Dietary Risk Assessment

A partially refined (using tolerance-level residues for all registered and proposed commodities 

and %CT data for some commodities) chronic dietary exposure assessment was conducted for 

the general U.S. population and various population subgroups. This assessment concludes that 
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the chronic dietary exposure estimates are below HED’s LOC (<100% cPAD) for the general 

U.S. population and all population subgroups. The chronic dietary exposure is estimated for the 

U.S. population at 8.3% of the cPAD and the most highly exposed population subgroup, children 

1-2 years old, at 28% of the cPAD. Additional refinements, such as inclusion of ARs and % 

market-share data for the proposed uses could be made in order to refine the chronic assessment. 

However, HED is confident that the assessment does not underestimate risk to the general U.S. 

population or any population subgroup.

5.4.4 Summary Table

Table 5.4.4. Summary of Dietary (Food and Drinking Water) Exposure and Risk for Imidacloprid.

Population Subgroup

Acute Dietary (95th Percentile) Chronic Dietary

Dietary Exposure 

(mg/kg/day) % aPAD Dietary Exposure(mg/kg/day) % cPAD

General U.S. Population 0.038591 28 0.004707 8.3

All Infants (<1 year old) 0.080374 57 0.007691 13

Children 1-2 years old 0.103801 74* 0.016205 28*

Children 3-5 years old 0.081638 58 0.011274 20

Children 6-12 years old 0.044966 32 0.006225 11

Youth 13-19 years old 0.026992 19 0.003594 6.3

Adults 20-49 years old 0.025911 18 0.003754 6.6

Adults 50-99 years old 0.025662 18 0.003812 6.7

Females 13-49 years old 0.025875 18 0.003725 6.5

*The subpopulation(s) with the highest risk estimates.

6.0 Residential (Non-Occupational) Exposure/Risk Characterization

The proposed use of imidacloprid on oyster beds in Washington State’s Willapa Bay and Grays 

Harbor is not expected to result in residential handler exposure (professionally applied), but can 

result in residential post-application exposures via potential contact with residues in the oyster 

bed water or sediment during recreational swimming, or in the case of subsistence fishermen or 

local Native American tribes, collecting oysters. These scenarios are consistent with the humanhealth risk assessment for an identical use pattern – applications of carbaryl to control burrowing 

shrimp in Willapa Bay and Grays Harbor (Memo, J. Dawson, 14-MAR-2003: D287532). There 

are no residential uses associated with the proposed Section 18 Emergency Exemption use on 

sugarcane.

For the purposes of evaluating aggregate (dietary and non-dietary) exposure for the proposed 

uses, imidacloprid has a variety of existing residential uses that should be considered, including 

residential lawns and gardens, indoor uses for bed bugs and crack-and-crevice treatments, pet 

uses (spot-on treatment and collars), and pre- and post-construction termiticide and wood 

preservative uses. Short-term dermal and inhalation handler exposures are expected. Generally, 

short-term dermal, inhalation, and incidental oral post-application exposures are expected, with 

the exception of intermediate- and long-term exposures from the pet collar use, as it presents the 

potential for prolonged exposure via a continuous source and frequent contact (i.e., playing with 

pets). Risks from these uses have been re-evaluated to reflect updates to HED’s 2012 

Residential SOPs (http://www.epa.gov/pesticides/science/residential-exposure-sop.html) along 

with policy changes for body weight assumptions. The revision of residential exposures will 

impact the human health aggregate risk assessment for imidacloprid.
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The registered and proposed residential uses were evaluated by HED and reviewed by the HED 

Science Advisory Council for Exposure (ExpoSAC; Memo, M. Crowley, 6-MAR-2012, 

D400191).

6.1 Residential Handler Exposure and Risk Estimates

HED uses the term “handlers” to describe those individuals who are involved in the pesticide 

application process. As the new use is expected to be professionally applied, residential handler 

exposure is not expected. For exposure to professional applicators as a result of the new use, see 

Section 9.1.

Unlike the proposed uses, however, existing residential uses, considered for the purposes of the 

aggregate risk assessment, are expected to result in residential handler exposure. HED believes 

that there are distinct tasks related to applications and that exposures can vary depending on the 

specifics of each task. Residential handlers are addressed somewhat differently by HED than 

occupational pesticide applicators as homeowners are assumed to complete all elements of an 

application without use of any protective equipment.

Risks from these uses have been estimated in past human-health risk assessments; however, have 

been re-evaluated to reflect updates to HED’s 2012 Residential SOPs and policy changes for 

body weight assumptions. The quantitative exposure/risk assessment developed for residential 

handlers for existing imidacloprid uses is based on the following scenarios: 

 Mixing/loading/applying liquid formulations for use with manually-pressurized 

handwands in indoor settings (bed-bug treatments and crack-and-crevice treatments);

 Mixing/loading/applying liquid formulations for use with hose-end sprayers on lawns and 

gardens;

 Mixing/loading/applying liquid formulations for use with a bucket or watering can to 

treat plant stems and tree trunks;

 Applications to gardens using a ready-to-use (RTU) trigger-spray bottle;

 Loading/applying granule formulations to lawns and gardens using a push-type/rotary

spreader;

 Applications of potting spikes and potting mediums to garden plants; and,

 Applications of spot-on treatments and collars to pets.

HED expects the duration of exposure for residential handlers to be short-term (1-30 days) in 

duration. Assessing exposures and risks resulting from residential uses is very similar to 

assessing occupational exposures and risks, except that a tiered approach for personal protection 

using increasing levels of personal-protective equipment (PPE) is not used in residential handler 

risk assessments. Homeowner handler assessments are based on the assumption that individuals 

are wearing shorts, short-sleeved shirts, socks, and shoes.

Table 6.1 below provides a summary of residential handler risk estimates from existing 

residential uses of imidacloprid, updated using the 2012 Residential SOPs and policy changes for 

body weigh assumptions. Short-term risk estimates for residential handlers are not of concern 

(MOEs >100).
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Table 6.1. Residential Handler Non-cancer Exposure and Risk Estimates for Existing Residential Uses of Imidacloprid.

Exposure Scenario MOE Level 

of Concern

Dermal Unit 

Exposure 

(mg/lb ai)

Inhalation 

Unit 

Exposure 

(mg/lb ai)

Maximum 

Application 

Rate1

Area Treated or 

Amount 

Handled Daily2

Dermal Inhalation Total

Dose 

(mg/kg/day)3 MOE4 Dose (mg/kg/day)5 MOE6 MOE7

Indoors

(bed bug and crack-andcrevice treatments)100 69 1.1 0.008 lb 

ai/gallon 0.5 gallons 0.00025 40,000 5.5E-05 180,000 33,000

Gardens 

/Trees

Hose-end 

sprayer

100 58 0.0014 0.5 lb ai/acre 1200 ft20.00072 14,000 2.4E-07 41,000,000 14,000

Watering 

can

100 58 0.0014 0.25 lb ai/gallon 1 gallon 0.013 770 4.4E-06 2,300,000 770

Potting 

medium 100 160 0.38 0.00288 lb ai/container 1 container 0.00041 24,000 1.4E-05 730,000 23,000

Potting 

spikes 100 160 0.38 0.00011 lb ai/spike 10 spikes 0.00016 63,000 5.2E-06 1,900,000 61,000

Triggerspray bottle 100 85.1 0.061 0.000189 lb 

ai/bottle 2 bottles 0.000029 350,000 2.9E-07 35,000,000 340,000

Rotary 

spreader 100 0.81 0.0026 0.4 lb ai/acre 1200 ft2

0.000008 1,200,000 3.6E-07 28,000,000 1,200,000

Pets Spot-on 100 120 Negligible 0.001 lb ai/pet 2 pets 0.00022 46,000 NA NA NA

Collar 100 120 Negligible 0.0099 lb ai/pet 2 pets 0.0021 4,700 NA NA NA

Lawns 

/Turf

Hose-end 

sprayer

100 13.4 0.022 0.5 lb ai/acre 0.5 acres 0.003 3,300 6.9E-05 150,000 3,200

Rotary 

spreader 100 0.81 0.0026 0.4 lb ai/acre 0.5 acres 0.00015 69,000 6.5E-06 1,500,000 66,000

1

See Table 4.2 for assessment reference.

2 Based on 2012 Residential SOPs. Departures from the SOP include the gardens/trees: watering-can scenario (per label, 1 gallon of solution treats 20 trees), the potting-medium scenario (per label, 1 

container = 20 lbs), and the potting-spike scenario (10 spikes considered a reasonable use estimate).

3 Dermal Dose = Dermal Unit Exposure (mg/lb ai) x Application Rate (lb ai/acre or gal) x Area Treated or Amount Handled (A or gallons/day) x DAF (%) / BW (kg).

4 Dermal MOE = Dermal NOAEL (mg/kg/day) / Dermal Dose (mg/kg/day).

5

Inhalation Dose = Inhalation Unit Exposure (mg/lb ai) x Conversion Factor (0.001 mg/ug) x Application Rate (lb ai/acre or gal) x Area Treated or Amount Handled (A or gallons/day) / BW (kg).

6

Inhalation MOE = Inhalation NOAEL (mg/kg/day) / Inhalation Dose (mg/kg/day).

7 Total MOE = NOAEL (mg/kg/day) / (Dermal Dose + Inhalation Dose) OR Total MOE = 1 / [(1/Dermal MOE) + (1/Inhalation MOE)].
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6.2 Post-Application Exposure and Risk Estimates

As a result of both the proposed use on oyster beds and from existing residential uses, there is the 

potential for post-application exposure for individuals exposed as a result of being in an 

environment that has been previously treated with imidacloprid.

Based on the proposed use pattern, only short-term post-application dermal, incidental oral, and 

inhalation exposures to imidacloprid residues in oyster bed water and sediment are expected. 

This assessment mimics those scenarios reviewed for an identical use pattern for the ai carbaryl 

(Memo, J. Dawson, 14-MAR-2003; D287532). The equations and inputs are generally derived 

from SWIMODEL 3.0, developed by EPA as a screening tool to conduct exposure assessments 

of pesticides found in swimming pools and spas and EPA’s Risk Assessment Guidance for 

Superfund – Part E, Supplemental Guidance for Dermal Risk Assessment (“RAGS-E”).

For the registered residential uses, in general, short-term dermal, inhalation, and incidental oral 

post-application exposures are expected. Intermediate- and long-term dermal, incidental oral and 

inhalation exposures are expected from the pet collar use, as it presents the potential for 

prolonged exposure via a continuous source and frequent contact (i.e., playing with pets). These 

risks were estimated in previous assessments (listed below, where applicable) but have been reevaluated here using the updated 2012 Residential SOPs and policy changes for body weight 

assumptions.

The quantitative exposure/risk assessment for residential post-application exposure is based on 

the following scenarios:

 As a result of the proposed use to control burrowing shrimp in Washington State’s 

Willapa Bay and Grays Harbor intertidal oyster beds:

o Ingestion of water during recreational swimming (both adults and children 3<6 

years old);

o Dermal exposure during recreational swimming (both adults and children 3<6 

years old);

o Dermal exposure to oyster bed sediment while collecting/harvesting oysters 

(adults) and playing (children 3<6 years old);

o Inhalation exposure during recreational swimming and/or collecting/harvesting 

oysters (both adults and children 3<6 years old); and,

o Incidental ingestion of sediment via hand-to-mouth activities (children 3<6 years 

old only).

 As a result of existing residential uses:

o Dermal exposure from contact with treated turf (both adults and children 11<16, 

6<11, and 1<2 years old) – updated from most recent risk assessment (Memo, G. 

Kramer et al., 16-MAR-2009; D375406);

o Dermal exposure from contact with treated gardens and trees (adults and children 

6<11 years old) – updated from most recent risk assessment (Memo, G. Kramer et 

al., 16-MAR-2009; D375406);
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o Dermal exposure from contact with treated mattresses (bed-bug treatments) and 

indoor surfaces (both adults and children 1<2 years old) – updated from most 

recent risk assessment (Memo, K. Lowe, 17-FEB-2009; D367396);

o Dermal exposure from contact with treated pets (both adults and children 1<2 

years old) – updated from most recent risk assessments (Memos, G. Kramer et al., 

16-MAR-2009, D375406 (spot-on); K. Lowe, 17-FEB-2009; D367396 (collar));

o Dermal exposure from contact with treated wood (both adults and children 1<2 

years old) – updated from most recent risk assessment (Memo, G. Kramer et al., 

16-MAR-2009; D375406);

o Inhalation exposure following mattress treatments and indoor crack-and-crevice 

treatments (both adults and children 1<2 years old) – updated from most recent 

risk assessment (Memo, K. Lowe, 17-FEB-2009; D367396);

o Incidental ingestion from contact with treated turf (children 1<2 years old only) –

updated from most recent risk assessment (Memo, G. Kramer et al., 16-MAR2009; D375406);

o Incidental ingestion from contact with treated indoor surfaces (children 1<2 years 

old only) – updated from most recent risk assessment (Memo, K. Lowe, 17-FEB2009; D367396);

o Incidental ingestion from contact with treated pets (children 1<2 years old only) –

updated from most recent risk assessments (Memos, G. Kramer et al., 16-MAR2009, D375406 (spot-on); K. Lowe, 17-FEB-2009; D367396 (collar)); and,

o Incidental ingestion from contact with treated wood (children 1<2 years old only) 

– updated from most recent risk assessment (Memo, G. Kramer et al., 16-MAR2009; D375406).

The lifestages (e.g., adults, children 1<2 years old, etc.) selected for each post-application 

scenario as a result of the registered uses are based on an analysis provided as Appendix A in the 

2012 Residential SOPs. The lifestages (adults and children 3<6 years old) selected for the postapplication scenarios as a result of the proposed oyster bed use are based on the expected 

potential for individuals to be in oyster beds and the activities they will conduct. In the case of 

Native American tribes and subsistence fishermen, it could be the case that families participate in 

these activities; thus, young children are considered as well. These lifestages are not the only 

lifestages that could be potentially exposed for these post-application scenarios; however, the 

assessment of these lifestages is health protective for the exposures and risk estimates for any 

other potentially exposed lifestages.

Table 6.2.1 below provides a summary of residential post-application risk estimates from the 

proposed use of imidacloprid on oyster beds. Table 6.2.2 below provides a summary of 

residential post-application risk estimates from existing residential uses of imidacloprid, updated 

using the 2012 Residential SOPs and policy changes for body weight assumptions.
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Table 6.2.1. Residential Post-application Non-cancer Exposure and Risk Estimates from the Proposed Use of 

Imidacloprid to Control Burrowing Shrimp.1

Use/Target Lifestage Post-application Exposure 

Scenario

Dose

(mg/kg-day) MOE

Combined Routes

(X indicates included 

in Combined MOE)

Combined MOE

WA State 

Willapa 

Bay and 

Grays 

Harbor 

Intertidal 

Oyster 

Beds

Adult 

Dermal (water) Swimming 5.6E-06 1,800,000 X

59,000

Dermal 

(sediment)

Oyster 

Harvesting 1.2E-04 85,000 X

Ingestion (water) 4.5E-05 220,000 X

Inhalation 3.7E-09 2,700,000,000 X

Children

3<6 years

Dermal (water) Swimming 7.3E-06 1,400,000 X

2,600

Dermal 

(sediment)

Playing in 

oyster bed 2.4E-03 4,200 X

Ingestion (water) 3.5E-04 28,000 X

Hand to Mouth (sediment) 1.1E-03 8,800 X

Inhalation 8.2E-09 1,200,000,000 X

1

 All MOEs represent short-term risk estimates. Intermediate- and long-term exposures are not expected from this use.

Table 6.2.2. Residential Post-application Non-cancer Exposure and Risk Estimates for Existing Residential 

Uses of Imidacloprid.

1

Use/Target Lifestage Post-application Exposure 

Scenario

Dose

(mg/kg-day)

MOE5

Combined Routes

(X indicates included in 

Combined MOE)

Combined 

MOE

Turf

(spray application)2

Adult Dermal

High-contact 

(playing) 0.014 740 --

NA Mowing 0.00026 36,000 --

Golfing 0.0011 9,400 --

Child 11<16 Dermal Mowing 0.00032 32,000 -- NA Golfing 0.0012 8,100 --

Child 6<11 Dermal Golfing 0.0015 6,900 -- NA

Child 1<2

Dermal (high-contact 

play) 0.027 370 X

Hand to Mouth 0.0076 1,300 X 290

Object to Mouth 0.00023 43,000 --

Incidental Soil Ingestion 1.7E-05 590,000 --

Gardens/ Trees (spray 

application)2

Adult Dermal 0.023 430 -- NA

Child 6<11 Dermal 0.016 630 -- NA

Indoor

Bed bug 

(mattress)

Adult Dermal 0.00059 17,000 -- NA

Child 1<2 Dermal 0.0013 7,400 -- NA

Crack-andcrevice

Adult

Dermal (playing on 

carpet)3 0.00088 11,000 X

6,200

Inhalation 0.0007 14,000 X

Child 1<2

Dermal (playing on 

carpet)3 0.00085 12,000 X

Inhalation 0.003 3,400 X 1,800

Hand to Mouth (playing 

on carpet)3 0.0018 5,700 X
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Table 6.2.2. Residential Post-application Non-cancer Exposure and Risk Estimates for Existing Residential 

Uses of Imidacloprid.1

Use/Target Lifestage Post-application 

Exposure Scenario

Dose

(mg/kg-day)

MOE5

Combined Routes

(X indicates included 

in Combined MOE)

Combined 

MOE

Pets

Spot-on

Adult

Dermal

(playing with small 

cat)4

0.0055 1,800 -- NA

Child 1<2

Dermal

(playing with small cat) 0.0139 720 X

630 Hand to Mouth (playing 

with small cat)4 0.0019 5,200 X

Collar

Adult

ST/IT

Dermal 

(playing with 

small cat)4

0.0028 3600 -- NA

LT

Dermal 

(playing with 

small cat)4

0.0028 2000 -- NA

Child 1<2

ST/IT

Dermal 

(playing with 

small cat)4

0.0071 1,400 X

1,200 Hand to Mouth 

(playing with 

small cat)4

0.00098 10,000 X

LT

Dermal 

(playing with 

small cat)4

0.0071 800 X

700 Hand to Mouth 

(playing with 

small cat)

4

0.00098 5,800 X

Wood Preservative / 

Termiticide

Adult Dermal

(playing on deck) 0.0184 540 -- NA

Child 1<2

Dermal

(playing on deck) 0.042 240 X

140 Hand to Mouth

(playing on deck) 0.028 360 X

1

See Appendix A for calculations and inputs.

2 Risk estimates presented only in this table for spray applications, as risks from uses of granule formulations are lower.

3 Risk estimates presented only in this table from contacting treated carpets, as risks from contacting other surfaces are lower.

4 Risk estimates presented only in this table from contacting small cats, as risks from other treated pets are lower.

5 MOEs are for short-term exposures only except for the pet collar which presents risks for short-/intermediate-term (ST/IT) and 

long-term (LT) exposures.

6.3 Combined Residential Risk Estimates (Multiple Exposure Scenarios)

Because of the potential likelihood for some uses to occur on the same day or over the same 

exposure duration, risks from some imidacloprid residential uses are combined to determine 

whether their co-occurrence presents a risk of concern. Residential handler and post-application 

scenarios are generally not combined. Although there is potential for the same individual (i.e., 

adult) to apply a pesticide in and around the home and be exposed by reentering a treated area in 

the same day, this is an unlikely exposure scenario, especially day after day for up to 30 days. 

Combining both of these exposure scenarios would also be inappropriate because of the 

conservative nature of each individual assessment.

There may be post-application residential exposure scenarios for a particular pesticide which 

could be combined for purposes of an aggregate exposure assessment. For imidacloprid, the 
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Page 28 of 45

outdoor treatments of lawns and gardens have a reasonable probability of co-occurring as do the 

indoor bed-bug and crack-and-crevice treatments. The likelihood of any of the existing 

residential uses to co-occur with exposures from the proposed oyster bed use is low, thus risk 

estimates are not presented. Table 6.3 presents combined risks for these scenarios, using a 

similar equation as shown in Section 6.2.1 and 6.2.2.

Table 6.3. Non-Cancer Residential Combined (Multiple Exposure Scenarios) Exposure and Risk Estimates for 

Imidacloprid.

Combined 

Exposure 

Scenario

Lifestage Exposure Scenario Route of 

Exposure Dose

Combined Total 

Dose

(mg/kg-day)

Combined Total 

MOEs

Outdoor 

Scenario 

(Turf/Garden)

Adult

Handler: Turf - Sprays Dermal 0.003

0.016 620 Inhalation 6.9E-05

Handler: Garden - Sprays Dermal 0.013

Inhalation 4.4E-06

Adult

Post-application: Turf -

Sprays Dermal 0.014

0.037 270 Post-application: Garden 

- Sprays Dermal 0.023

Bedbug Scenario

Adult

Post-application: 

Perimeter Dermal 0.00088

0.0022 4,500 Post-application: 

Mattress Dermal 0.00059

Post-application: 

Perimeter/Mattress Inhalation 0.0007

Child

Post-application: 

Perimeter

Dermal 0.00085

0.0069 1,500

Hand to Mouth 0.0018

Post-application: 

Mattress Dermal 0.0013

Post-application: 

Perimeter/Mattress Inhalation 0.003

6.4 Residential Risk Estimates for Use in Aggregate Assessment

The residential scenarios listed below should be used for the aggregate (dietary + non-dietary) 

assessment. Table 6.4 presents the risk estimates.

 The recommended residential exposure for use in the short-term adult aggregate 

assessment reflects combined dermal post-application exposures from contacting treated 

lawns and gardens. For the long-term adult aggregate assessment, the recommended 

residential exposure scenario is contacting treated pets following applications of pet 

collars.

 The recommended residential exposure for use in the short-term children 1<2 years old 

aggregate assessment reflects combined dermal and hand-to-mouth exposures from 

contacting treated wood surfaces (e.g., playing on decks). For the long-term children 1<2 

years old aggregate assessment, the recommended residential exposure scenario is 

contacting treated pets following application of pet collars.
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Table 6.4. Recommendations for the Residential Exposures for the Imidacloprid Aggregate Assessment.1

Lifestage

Handler Exposure (mg/kg/day)2 Residential 

Handler Total 

Exposure 

(mg/kg/day)3

Residential 

Handler 

Total MOE

Post-application Exposure 

(mg/kg/day)4

Residential 

Post-application 

Total Exposure 

(mg/kg/day)

Residential 

Postapplication 

MOE Dermal Inhalation Dermal Inhalation Oral 5

Short-/Intermediate-Term

Adult 0.016 0.0001 0.016 620 0.037 N/A N/A 0.037 270

Child 1<2 N/A N/A N/A N/A 0.042 N/A 0.028 0.07 140

Long-Term

Adult N/A N/A N/A N/A 0.0028 N/A N/A 0.0028 2,000

Child 1<2 N/A N/A N/A N/A 0.0071 N/A 0.00098 0.0081 700

1 Bolded risk estimates should contribute to the residential exposure portion of the aggregate assessment. 

2 Handler exposure is the combined lawn and garden uses presented in Section 5.3 – this was the handler scenario with the highest exposures.

3

For adults, residential total exposure combines the highest dermal and inhalation exposures (Table 5.1.1, 5.2.1, 5.2.2, and 5.2.3), where applicable. For children, total residential 

exposure combines high-end post application incidental oral AND dermal exposure, where applicable (Table 5.2.1, 5.2.2, 5.3.1).

4 Total MOE = 1 / (1/Dermal MOE) + (1/Inhalation MOE).

5

Post-application exposure represents high-end dermal, inhalation and/or incidental oral exposure for the relevant exposure duration.

6 Total MOE = 1 / (1/Dermal MOE) + (1/Inhalation MOE) + (1/Incidental oral MOE).
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6.5 Residential Bystander Post-application Inhalation Exposure

Post-application inhalation exposure while swimming in intertidal oyster beds was assessed for 

the proposed use of imidacloprid. However, bystander inhalation exposure was not assessed for 

the existing agricultural uses of imidacloprid. Based on the Agency's current practices, a 

quantitative post-application inhalation exposure assessment was not performed at this time 

primarily because of the low acute inhalation toxicity (Toxicity Category IV) and low vapor 

pressure (4 x 10-7 mmHg). However, volatilization of pesticides may be a source of postapplication inhalation exposure to individuals nearby pesticide applications. The Agency sought 

expert advice and input on issues related to volatilization of pesticides from its Federal 

Insecticide, Fungicide, and Rodenticide Act (FIFRA) Scientific Advisory Panel (SAP) in 

December 2009, and received the SAP’s final report on March 2, 2010 

(http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The Agency is in the 

process of evaluating the SAP report and may, as appropriate, develop policies and procedures to 

identify the need for and, subsequently, the way to incorporate post-application inhalation 

exposure into the Agency's risk assessments. If new policies or procedures are developed, the 

Agency may revisit the need for a quantitative post-application inhalation exposure assessment 

for the existing uses of imidacloprid.

6.6 Spray Drift

Spray drift is always a potential source of exposure to residents nearby to spraying operations. 

This is particularly the case with aerial application, but, to a lesser extent, could also be a 

potential source of exposure from the ground application method employed for imidacloprid. 

The Agency has been working with the Spray Drift Task Force, EPA Regional Offices, and State 

Lead Agencies for pesticide regulation and other parties to develop the best spray-driftmanagement practices (see the Agency’s Spray Drift website for more information at 

http://www.epa.gov/opp00001/factsheets/spraydrift.htm). The Agency has completed its 

evaluation of the new database submitted by the Spray Drift Task Force, a membership of U.S. 

pesticide registrants, and is developing a policy on how to appropriately apply the data and the 

AgDRIFT®computer model to its risk assessments for pesticides applied by air, orchard airblast,

and ground hydraulic methods. After the policy is in place, the Agency may impose further 

refinements in spray-drift-management practices to reduce off-target drift with specific products 

with significant risks associated with drift.

Note that an application rate of 0.5 lb ai/A was used in the updated assessment of the existing 

lawn/turf registration to estimate post-application residential exposure of children. As this rate is 

equal to or higher than the registered and proposed uses, the exposures resulting from direct 

application to lawns/turf are likely protective of any exposure via spray drift from the proposed 

oyster-bed use.

7.0 Aggregate Exposure/Risk Characterization

In accordance with the FQPA, HED must consider and aggregate pesticide exposures and risks 

from three major sources: food, drinking water, and residential exposures. In an aggregate 

assessment, exposures from relevant sources are added together and compared to quantitative 
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estimates of hazard (e.g., a NOAEL or PAD), or the risks themselves can be aggregated. When 

aggregating exposures and risks from various sources, HED considers both the route and 

duration of exposure. In the case of imidacloprid, aggregate risk assessments were performed for 

acute aggregate exposure (food + drinking water), short-term aggregate exposure (food + 

drinking water + residential), and chronic aggregate exposure (food + drinking water + 

residential). Although there are intermediate-term residential exposures, an intermediate-term 

aggregate was not quantitatively assessed since (1) the short- and intermediate-term points of 

departure are the same and (2) the short-term aggregate represents worst-case residential 

exposures. For these reasons, the short-term aggregate is protective of the longer-term 

exposures. A cancer aggregate risk assessment was not performed because imidacloprid is not 

carcinogenic. All potential exposure pathways were assessed in the aggregate risk assessment. 

7.1 Acute Aggregate Risk

The acute aggregate risk assessment takes into account exposure estimates from dietary

consumption of imidacloprid (food and drinking water). The dermal, inhalation, and incidental 

oral exposures resulting from short-term residential applications are assessed separately. The 

acute dietary exposure estimates are below HED’s LOC (<100% aPAD) at the 95th exposure 

percentile for the general U.S. population (28% of the aPAD) and all other population subgroups 

(see Table 5.4.4). The most highly-exposed population subgroup is children 1-2 years old, at 

74% of the aPAD. Therefore, the acute aggregate risk associated with the proposed use of 

imidacloprid does not exceed HED’s LOC for the general U.S. population or any population 

subgroups.

7.2 Short-Term Aggregate Risk

The short-term aggregate risk assessment estimates risks likely to result from 1- to 30-day

exposures to imidacloprid residues from food, drinking water, and residential pesticide uses. 

High-end estimates of residential exposure are used, and average values are used for food and 

drinking water exposures.

Short-term aggregate risk assessments are necessary for both adults and children as there is 

potential for both short-term dermal and inhalation handler exposure, and short-term postapplication exposure from the residential uses of imidacloprid. For the short-term aggregate risk 

assessment, potential residential post-application exposures were combined with food and 

drinking water exposures. 

For adults, the combined dermal post-application exposures from contacting treated lawns and 

gardens resulted in the highest short-term exposure (exposure = 0.037 mg/kg/day; MOE = 270

see Table 6.4). For children, the combined dermal and hand-to-mouth exposure from contacting 

treated wood surfaces resulted in the highest short-term exposure (exposure= 0.07 mg/kg/day, 

MOE = 140; see Table 6.4). Therefore, these short-term exposure estimates were aggregated 

with the chronic dietary (food) to provide a worst-case estimate of short-term aggregate risk for 

the general U.S. population and children 1-2 years old (the child population subgroup with the 

highest estimated chronic dietary food exposure) (see Table 5.4.4). As the short-term aggregate 

MOEs are greater than 100, risks are not of concern.
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Table 7.2. Short-Term Aggregate Risk Calculations.

Population NOAEL 

(mg/kg/day)

LOC1

Max 

Allowable 

Exposure2

(mg/kg/day)

Average Food 

and Drinking 

Water 

Exposure 

(mg/kg/day)

3

Residential 

Exposure 

(mg/kg/day)

4

Total 

Exposure 

(mg/kg/day)

5

Aggregate 

MOE (food, 

water, and 

residential)6

Adults 10 100 0.1 0.004707 0.037 0.041707 240

Children 1-2 years 

old 10 100 0.1 0.016205 0.07 0.086205 120

1

 The level of concern (target MOE) includes 10X for interspecies extrapolation and 10X for intraspecies variation.

2

 Maximum Exposure (mg/kg/day) = NOAEL/LOC.

3

 Avg. Dietary Exposure. See Table 5.4.4.

4

 Residential Exposure = Dermal exposure for adults and Oral + Dermal exposure for children.. See Table 6.4.

5

 Total exposure = Avg. Dietary Exposure + Residential Exposure.

6 Aggregate MOE = NOAEL ÷ Total Exposure.

7.3 Intermediate-Term Aggregate Risk

The intermediate-term aggregate risk assessment estimates risks likely to result from 30 days to 6 

months exposure to imidacloprid residues from food, drinking water, and residential pesticide 

uses. High-end estimates of residential exposure are used, and average values are used for food 

and drinking water exposures.

Although there is potential for intermediate-term residential exposure from the registered pet 

collar use, an intermediate-term aggregate assessment is not required. The short- and 

intermediate-term toxicological endpoints are the same, and the exposures assessed in the shortterm aggregate (adults- combined dermal post-application exposures from contacting treated 

lawns and gardens; and children - combined dermal and hand-to-mouth from contacting treated 

wood surfaces) provide a worst-case estimate of short-term residential exposure. Therefore, the 

estimates of risk for short-term duration exposures are protective of those for intermediate-term 

duration exposures.

7.4 Chronic Aggregate Risk

The chronic aggregate risk assessment takes into account average exposure estimates from 

dietary consumption of imidacloprid (food and drinking water) and long-term residential uses. 

High-end estimates of residential exposure are used, and average values are used for food and 

drinking water exposures.

Based on the proposed and existing use patterns, there is potential for long-term residential 

exposure from the pet-collar use, as it presents the potential for prolonged exposure via a 

continuous source and frequent contact (i.e., playing with pets). For adults, the dermal postapplication exposure from contacting treated pets resulted in a long-term exposure of 0.0028

mg/kg/day (MOE = 2,000; see Table 6.4). For children, the combined dermal and hand-tomouth from contacting treated pets resulted in a combined long-term exposure of 0.0081 

mg/kg/day (MOE = 700; see Table 6.4). Therefore, these long-term exposure estimates were 

aggregated with the chronic dietary (food) to provide a worst-case estimate of chronic aggregate 

risk for the general U.S. population and children 1-2 years old (the child population subgroup 

with the highest estimated chronic dietary food exposure) (see Table 7.4). As the chronic 

aggregate MOEs are greater than 100, risks are not of concern.
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Table 7.4. Chronic Aggregate Risk Calculations.

Population

Chronic/Long-Term Scenario

NOAEL 

(mg/kg/day)

LOC1

Max 

Allowable 

Exposure2

(mg/kg/day)

Average Food 

and Drinking 

Water 

Exposure 

(mg/kg/day)

3

Residential 

Exposure 

(mg/kg/day)

4

Total 

Exposure 

(mg/kg/day)

5

Aggregate 

MOE (food, 

water, and 

residential)6

Adults 5.7 100 0.057 0.004707 0.0028 0.007507 760

Children 1-2 years 

old 5.7 100 0.057 0.016205 0.0081 0.024305 230

1

 The level of concern (target MOE) includes 10X for interspecies extrapolation and 10X for intraspecies variation.

2

 Maximum Allowable Exposure (mg/kg/day) = NOAEL/LOC.

3

 Avg. Dietary Exposure. See Table 5.4.4.

4

 Residential Exposure = Dermal exposure for adults and Oral + Dermal exposure for children. See Table 6.4. 

5

 Total exposure = Avg. Dietary Exposure + Residential Exposure.

6

 Aggregate MOE = NOAEL ÷ Total Exposure.

8.0 Cumulative Exposure/Risk Characterization

Unlike other pesticides for which EPA has followed a cumulative risk approach based on a 

common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as 

to imidacloprid and any other substances and imidacloprid does not appear to produce a toxic 

metabolite produced by other substances. For the purposes of this tolerance action, therefore, 

EPA has not assumed that imidacloprid has a common mechanism of toxicity with other 

substances. For information regarding EPA’s efforts to determine which chemicals have a 

common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the 

policy statements released by EPA’s Office of Pesticide Programs concerning common 

mechanism determinations and procedures for cumulating effects from substances found to have 

a common mechanism on EPA’s website at http://www.epa.gov/pesticides/cumulative/.

9.0 Occupational Exposure/Risk Characterization

Based on the proposed application scenarios and toxicological considerations, non-cancer 

occupational handler (dermal and inhalation) assessments were conducted for the proposed uses 

on oyster beds and sugarcane; and occupational post-application (dermal) assessments were 

conducted for the proposed sugarcane use. The proposed Section 3 use on oyster beds and 

Section 18 Emergency Exemption use on sugarcane were evaluated by HED and were reviewed 

by the HED ExpoSAC (Memo, M. Crowley, 6-MAR-2012, D400191; and J. Tyler, 7-MAR2012; D407182).

9.1 Handler Exposure and Risk Estimates

HED uses the term handlers to describe those individuals who are involved in the pesticide 

application process. HED believes that there are distinct job functions or tasks related to 

applications and exposures can vary depending on the specifics of each task. Job requirements 

(amount of chemical used in each application), the kinds of equipment used, the target being 

treated, and the level of protection used by a handler can cause exposure levels to differ in a 

manner specific to each application event. 
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Based on the anticipated use patterns, potential occupational handler exposure scenarios include: 

 As a result of the proposed Section 3 use on oyster beds:

o Mixing/loading the liquid formulation to support aerial and groundboom 

applications;

o Mixing/loading the granule formulation to support aerial and tractor-drawn 

spreader applications;

o Applications of the granule and diluted liquid formulation using aerial equipment;

o Applications of the diluted liquid formulation with groundboom sprayers;

o Applications of the granule formulation using tractor-drawn spreaders;

o Flagging for aerial applications of the granule and diluted liquid formulation;

o Mixing/loading/applying the liquid formulation with a backpack sprayer; and,

o Loading/applying the granule formulation with a belly grinder or rotary spreader.

 As a result of use on the proposed Section 18 Emergency Exemption on sugarcane:

o Mixing/loading liquids to support aerial applications, 

o Applying liquids with enclosed cockpit aerial equipment, and

o Flagging to support aerial applications. 

For the proposed use of imidacloprid to control burrowing shrimp, only short-term exposures are 

expected due to the limited geographical area of the applications (Willapa Bay and Grays Harbor 

in Washington State) and the limit of one application per acre per year. As a result, it is unlikely

that an individual would make repeated daily applications for 1-6 months for this use. Shortterm exposure is also anticipated for the proposed sugarcane use as the use directions limit 

application to 2 per crop cycle. However, the short- and intermediate-term toxicological 

endpoints are the same; therefore, the estimates of risk for short-term duration exposures are 

protective of those for intermediate-term duration exposures. Long-term exposures are not 

expected; therefore, a long-term assessment was not conducted. The average adult body weight 

of 80 kg was used for estimating dermal and inhalation doses.

No chemical-specific handler exposure data were submitted in support of this Section 3 

registration. It is the policy of HED to use the best available data to assess handler exposure. 

Sources of generic handler data, used as surrogate data in the absence of chemical-specific data, 

include PHED 1.1, the AHETF database, the ORETF database, or other registrant-submitted 

occupational exposure studies. Some of these data are proprietary (e.g., AHETF data), and 

subject to the data protection provisions of FIFRA. The standard values recommended for use in 

predicting handler exposure that are used in this assessment, known as “unit exposures,” are 

outlined in the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” 

(http://www.epa.gov/opp00001/science/handler-exposure-table.pdf), which, along with 

additional information on HED policy on use of surrogate data, including descriptions of the 

various sources, can be found at http://www.epa.gov/pesticides/science/handler-exposuredata.html.

Occupational handler exposure assessments are completed by HED using different levels of risk 

mitigation. Typically, HED uses a tiered approach. The lowest tier is designed as the “baseline”
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exposure scenario (i.e., long-sleeve shirt, long pants, shoes, socks, no respirator). If risk 

estimates are of concern at baseline attire, then increasing levels of PPE (i.e., gloves, respirators) 

are evaluated. If risk estimates remain a concern with maximum PPE, then engineering controls 

(i.e., enclosed cabs or cockpits, water-soluble packaging, and closed mixing/loading systems) are 

evaluated. This approach is used to ensure that the lowest level of risk mitigation that provides 

adequate protection is selected, since the addition of PPE and engineering controls involves an 

additional expense to the user and (in the case of PPE) also involves an additional burden to the 

user due to decreased comfort and dexterity and increased heat stress and respiratory stress. The 

proposed imidacloprid product labels direct mixers, loaders, applicators and other handlers to 

wear a long-sleeved shirt, long pants, shoes plus socks and chemical-resistant gloves. In 

addition, the label for the granule formulation directs users to wear a dust mask.

PP#2E7988: Table 9.1.1 provides a summary of the estimated exposures and risks to 

occupational pesticide handlers resulting from the use on oyster beds. All dermal and inhalation 

risk estimates for occupational handlers are above the LOC (MOEs >100) with baseline 

protection (i.e., long-sleeve shirt, long pants, shoes, and socks) and chemical-resistant gloves. 

Only engineering control data (i.e., enclosed cockpits) are available for aerial application 

scenarios. All dermal and inhalation risk estimates for occupational aerial applicators are above 

the LOC (MOEs >100) with baseline clothing and enclosed cockpits.

PP#12LA11: Table 9.1.2 provides a summary of the estimated exposures and risks to 

occupational pesticide handlers resulting from the use on sugarcane. For the scenarios where 

baseline data are available, all dermal and inhalation risk estimates for occupational handlers are 

above the LOC (MOEs >100) with baseline protection (i.e., long-sleeve shirt, long pants, shoes, 

and socks). Only engineering control data (i.e., enclosed cockpits) are available for aerial 

application scenarios. All dermal and inhalation risk estimates for occupational aerial 

applicators are above the LOC (MOEs >100) with baseline clothing and enclosed cockpits.

The Agency has evaluated scenarios that may be limited in nature such as flagging during aerial 

applications because engineering controls (i.e., Global Positioning Satellite technology) are now 

predominantly used as indicated by the 1998 National Agricultural Aviation Association 

(NAAA) survey of their membership. It appears, however, flaggers are still used in 

approximately 10-15% of aerial application operations. In cases like these, the Agency strongly 

encourages the use of the engineering control system but will continue to evaluate risks for 

flaggers and any other population where a clear exposure pathway exists until the potential for 

exposure is eliminated. The Agency is aware that NAAA is conducting another survey on 

exposure issues and will consider those results as are timely and appropriate.
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Table 9.1.1. Short-Term Occupational Exposure and Risk Estimates for Imidacloprid Applications to WA Oyster Beds.

Exposure Scenario

Dermal Unit 

Exposure (ug/lb ai)1

Inhalation Unit 

Exposure (ug/lb ai)1 Maximum 

Application 

Rate2

Area 

Treated or 

Amount 

Handled 

Daily3

Dermal Inhalation Total

Mitigation Level Mitigation Level Dose 

(mg/kg/day)4 MOE5 Dose (mg/kg/day)6 MOE7 MOE8

Mixer/Loader

Granules

Aerial applications 6.9

[Baseline, CR gloves]

1.7

[No respirator] 0.5 lb ai/acre

1200 acres 0.0037 2,700 0.0128 780 610

Tractor-drawn spreader 

applications 200 acres 0.00062 16,000 0.00213 4,700 3,600

Liquids Aerial applications 37.6

[Baseline, CR gloves]

0.219

[No respirator]

1200 acres 0.0203 490 0.00164 6,100 450

Groundboom applications 200 acres 0.0034 3,000 0.00027 36,000 2,800

Applicator

Granules

Aerial applications

1.7

[Engineering control 

(enclosed cockpit)]

1.3

[Engineering control 

(enclosed cockpit)]

0.5 lb ai/acre

1200 acres 0.00092 11,000 0.00975 1,000 920

Tractor-drawn spreader 

applications

7.2

[Baseline, CR gloves]

1.2

[No respirator] 200 acres 0.00065 15,000 0.0015 6,700 4,600

Liquids

Aerial applications

5

[Engineering control 

(enclosed cockpit)]

0.068

[Engineering control 

(enclosed cockpit)]

1200 acres 0.0027 3,700 0.00051 20,000 3,100

Groundboom applications 16.1

[Baseline, CR gloves]

0.34

[No respirator] 200 acres 0.0015 6,900 0.000085 190,000 5,400

Flagger

Granules Aerial applications 2.73

[Baseline, CR gloves]

0.15

[No respirator] 0.5 lb ai/acre

350 acres 0.00189 23,000 0.00033 30,000 13,000

Liquids Aerial applications 12

[Baseline, CR gloves]

0.35

[No respirator] 350 acres 0.00043 5,300 0.00077 13,000 3,800

Mixer/loader/Applicator

Liquids Backpack sprayer 8260

[Baseline, CR gloves]

2.58

[No respirator]

0.1 lb 

ai/gallon 40 gallons 0.0297 340 0.000129 78,000 340

Granules

Belly grinder 9300

[Baseline, CR gloves]

62

[No respirator] 0.5 lb ai/acre

1 acre 0.00419 2,400 0.000388 26,000 2,200

Rotary spreader 240

[Baseline, CR gloves]

10

[No respirator] 5 acres 0.00054 19,000 0.000313 32,000 12,000

1 Unit exposures from PHED/ORETF/AHETF/etc. See: http://www.epa.gov/pesticides/science/handler-exposure-data.html. Baseline = single-layer (SL) of clothing (long-sleeve shirt, long pants, 

shoes/socks). CR = chemical-resistant.

2 Based on proposed labels.

3 Exposure Science Advisory Council Policy #9.1.

4 Dermal Dose = Dermal Unit Exposure (ug/lb ai) x Conversion Factor (0.001 mg/ug) x Application Rate (lb ai/acre or gal) x Area Treated or Amount Handled (A or gal/day) x DAF (%) / BW (kg).

5 Dermal MOE = Dermal NOAEL (mg/kg/day)/Dermal Dose (mg/kg/day).

6

Inhalation Dose = Inhalation Unit Exposure (ug/lb ai) x Conversion Factor (0.001 mg/ug) x Application Rate (lb ai/acre or gal) x Area Treated or Amount Handled (A or gal/day) / BW (kg).

7

Inhalation MOE = Inhalation NOAEL (mg/kg/day)/ Inhalation Dose (mg/kg/day).

8 Total MOE = 1/(1/Dermal MOE + 1/Inhalation MOE). 
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Table 9.1.2. Short-Term Occupational Exposure and Risk Estimates for Imidacloprid Applications to

Sugarcane in LA.

Crop or

Target

Unit Exposure1

(μg ai/lb handled)

Application 

Rate2

(lb ai/A)

Units 

Treated3

(A/day)

Avg. Daily Dose4

(mg ai/kg bw/day)

Short-term 

MOEs5

Total 

MOE6

Mixer/Loader – Liquid – Aerial Applications

Sugarcane

Dermal

Baseline6: 220 0.08 1200

Dermal

Baseline: 0.019

Dermal

Baseline: 530 520 Inhalation

Baseline: 0.219

Inhalation

Baseline: 0.00026

Inhalation 

Baseline: 38,000

Applicator – Aerial Applications

Sugarcane

Dermal

Eng. Control8: 5.0

0.08 1200

Dermal

Baseline: 0.00432

Dermal

Baseline: 23,000

19,000 Inhalation

Eng. Control: 0.065

Inhalation

Baseline: 0.000082

Inhalation

Baseline: 

120,000

Flagger

Sugarcane

Dermal

Baseline: 11 0.08 350

Dermal

Baseline: 0.00028

Dermal

Baseline: 36,000 25,000 Inhalation

Baseline: 0.35

Inhalation

Baseline: 0.00012

Inhalation

Baseline: 82,000

1 Unit Exposures are taken from “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table,” March, 2012. 

2 Application Rate. = Taken from proposed use information. 

3 Units Treated are taken from “Standard Values for Daily Acres Treated in Agriculture”; ExpoSAC SOP No. 9.1, revised 25 September 

2001.

4 Average Daily Dose = Unit Exposure * Applic. Rate * Units Treated * Absorption factor (dermal only = 7.2%)  80 kg Body Weight. 

5 MOE = Margin of Exposure = NOAEL  ADD. NOAEL = 10 mg/kg bw/day (dermal), 10 mg/kg bw/day (inhalation).

6 Total MOE = NOAEL  (Combined Dermal + Inhalation Dose).

7 Baseline = Long-sleeve shirt, long pants, and no gloves (dermal); no respirator (inhalation).

8 Engineering Control = enclosed cockpit and baseline attire (long-sleeve shirt, long pants, shoes, and socks).

9.2 Post-Application Exposure and Risk Estimates

HED uses the term post-application to describe exposures that occur when individuals are 

present in an environment that has been previously treated with a pesticide (also referred to as reentry exposure). Such exposures may occur when workers enter previously treated areas to 

perform job functions, including activities related to crop production, such as scouting for pests 

or harvesting. Post-application exposure levels vary over time and depend on such things as the 

type of activity, the nature of the crop or target that was treated, the type of pesticide application, 

and the chemical’s degradation properties. In addition, the timing of pesticide applications, 

relative to harvest activities, can greatly reduce the potential for post-application exposure.

For the proposed Section 3 use of imidacloprid on oyster beds, the extent of post-application 

exposure is expected to be non-occupational in nature. Thus, any occupational post-application 

dermal or inhalation exposures (e.g., during oyster harvesting) are adequately covered by the 

residential post-application assessment in Section 6.2. Based on the proposed Section 18 

Emergency Exemption use of imidacloprid on sugarcane, occupational post-application dermal 

exposures are expected. 

9.2.1 Dermal Post-application Exposure and Risk Estimates

HED expects that post-application exposure will occur since imidacloprid is applied as a foliar 

spray. Post-application exposure is expected to be short-term based on information provided on 
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Page 38 of 45

the label (a maximum of 2 applications per crop cycle). However, the short- and intermediateterm toxicological endpoints are the same; therefore, the estimates of risk for short-term duration 

exposures are protective of those for intermediate-term duration exposures. 

It is the policy of HED to use the best available data to assess post-application exposure. 

Sources of generic post-application data, used as surrogate data in the absence of chemicalspecific data, are derived from ARTF exposure monitoring studies, and, as proprietary data, are 

subject to the data protection provisions of FIFRA. The standard values recommended for use in 

predicting post-application exposure that are used in this assessment, known as “transfer 

coefficients,” are presented in the “Science Advisory Council for Exposure (ExpoSAC) Policy

3” (http://www.epa.gov/pesticides/science/exposac_policy3.pdf), which, along with additional 

information about the ARTF data, can be found at http://www.epa.gov/pesticides/science/postapp-exposure-data.html.

A summary of the post-application MOEs and respective reentry intervals is provided in Table 

9.2.1. The short-term post-application assessments for sugarcane resulted in MOEs of 100 or 

greater on “day 0” (immediately after application) for all exposure activities, and are not of 

concern.

Table 9.2.1. Summary of Short-term Occupational Post-application Risk Estimates.

Crop/Site Transfer Coefficient 

(cm2/hr)

Application Rate 

(lb ai/A)

DFR on Day 

0 (ug/cm2)

Day 0 ST 

MOE2

Day X at which 

ST MOE ≥ LOC

Sugarcane

70 (hand weeding)

0.08 0.224

88,000 0

1100 (scouting) 5,600 0

17,600 (hand harvesting) 350 0

1 DFR = AR x F x (1-D)t

x 4.54E8 μg/lb x 2.47E-8 acre/cm2.

2 MOE = POD (NOAEL, 10 mg/kg/day) / Daily Dermal Dose. Daily Dermal Dose = [DFR (μg/cm2

) x TC x 0.001 mg/μg x 8 hrs/day x 7.2% 

dermal absorption]  body weight 80 kg adult). 

9.2.2 Inhalation Post-application Exposure and Risk Estimates

Based on the Agency's current practices, a quantitative inhalation post-application inhalation 

exposure assessment was not performed at this time primarily because of the low acute 

inhalation toxicity (Toxicity Category IV) and low vapor pressure (4 x 10-7 mmHg). However, 

there are multiple potential sources of post-application inhalation exposure to individuals 

performing post-application activities in previously treated areas. These potential sources 

include volatilization of pesticides and resuspension of dusts and/or particulates that contain 

pesticides. The Agency sought expert advice and input on issues related to volatilization of 

pesticides from its FIFRA SAP in December 2009, and received the SAP’s final report on March 

2, 2010 (http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The Agency is 

in the process of evaluating the SAP report as well as available post-application inhalation 

exposure data generated by the ARTF and may, as appropriate, develop policies and procedures, 

to identify the need for and, subsequently, the way to incorporate occupational post-application 

inhalation exposure into the Agency's risk assessments. If new policies or procedures are put 

into place, the Agency may revisit the need for a quantitative occupational post-application 

inhalation exposure assessment for imidacloprid.
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10.0 References

J. Alsadek, 2-AUG-2012, D403995, Usage Report Package in Support of Registration for the 

Insecticide Imidacloprid (129099).

M. Crowley, 6-MAR-2013, D400191, Occupational and Residential Exposure Assessment for a 

Proposed Use to Control Burrowing Shrimp in Oyster Beds.

J. Dawson, 14-MAR-2003, D287532, Carbaryl: Revised HED Risk Assessment - Phase 5- Public 

Comment Period, Error Correction Comments Incorporated.

Y. Donovan, 23-MAR-1999, D242320, PP# 8F04940. Imidacloprid - Proposal for Tolerances of 

Residues in/on Citrus Crop group and Processed Commodities; in/on Leafy Petiole Vegetables: 

Residue Chemistry Review.

F. Griffith, 15-JUN-1993, D193027, Multiresidue Method (MRM) Validation Data For 

Imidacloprid (Confidor®).

F. Griffith, 18-JUN-1993, D187911, PP# 3F4169 - Imidacloprid (Confidor®) on Apples, 

Cottonseed, Potatoes, Meat, Milk, Poultry, and Eggs. Review of the Analytical Method and

Petitioner's February 5, 1993 Letter.

F. Griffith, 25-JUN-1993, TXR# 0050886, Metabolism Committee Meeting Held on June 22, 

1993: Metabolism of Imidacloprid.

F. Griffith, 15-JUL-1993, D193005, Multiresidue Method (MRM) Validation Data for 

Imidacloprid (Confidor®).

F. Griffith, 20-SEP-1993, D185148, Imidacloprid (Confidor®) on Apples, Cottonseed, Potatoes,

Meat, Milk, Poultry, and Eggs. Review of Residue Data and Analytical Method.

F. Griffith, 1-JUN-1994, D202113, Imidacloprid (Admire®) on Apples, Cotton-seed, Potatoes, 

Meat, Milk, poultry, and Eggs. Evaluation of the Tolerance Method Validation Report.

F. Griffith, 8-JUN-1994, D200233, Imidacloprid (Admire®) on Apples, Potatoes, Cottonseed, 

Meat, Milk, Poultry, and Eggs. Review of the March 1 and April 11, 1994, Amendments.

F. Griffith, 22-JUN-1994, D194206, Imidacloprid (Admire®) on the Fruiting Vegetables and 

Brassica (Cole) Leafy Vegetables Crop Groups, Lettuce, Grapes and Grape Processed 

Commodities, Tomato Processed Commodities, Meat, Milk, Poultry, and Eggs. Review of the 

Residue Data and Analytical Method.

F. Griffith, 16-MAY-1995, D212683, Imidacloprid (Gaucho®) on barley, wheat, and sugarbeets 

following seed treatment. Review of the January 19, March 8 and 28, 1995 Amendments.
Imidacloprid Human-Health Risk Assessment DP#s 399719 and 407172

Page 40 of 45

F. Griffith, 8-JUN-1995, D213252, Imidacloprid (Admire®) on Citrus Fruits Crop Group and 

Pecans. Review of the Residue Data and Analytical Method.

F. Griffith, 18-DEC-1995, D221591, Imidacloprid (Admire®) in citrus fruits crop group; and 

apples, cottonseed and potatoes. Evaluation of the Tolerance Method Validation Report.

F. Griffith, 29-FEB-1996, D217632, Imidacloprid on Tobacco. Amended Registration Request 

and the February 26, 1996 Amendment.

G. Kramer et al., 16-MAR-2009, D375406, Revised Human-Health Risk Assessment for 

Proposed Section 3 Seed Treatment Uses on Bulb Vegetables (Crop Group 3); Cereal Grains 

(Crop Group 15); Root and Tuber Vegetables, Except Sugar Beet (Crop Subgroup 1B); Tuberous 

and Corm Vegetables (Crop Subgroup 1C); Leafy Vegetables, Except Brassica (Crop Subgroup 

4A); Brassica Vegetables (Crop Group 5); Fruiting Vegetables (Crop Group 8); Cucurbit 

Vegetables (Crop Group 9), and Residential Crack and Crevice and Bed-Bug Uses.

K. Lowe, 17-FEB-2009, D367396, Imidacloprid: Occupational and Residential Risk Assessment 

for Proposed Bed Bug Use and an Assessment for a Crack and Crevice Use.

J. Melendez, 22-JULY-2009, Tier I Estimated Environmental Concentrations of Imidacloprid for 

the Use in the Human Health Risk Assessment, Registration of a New Product for Seed 

Treatment, Sepresto 75WS, and New Use on Bulb Vegetables (Crop Group 3) for GAUCHO 

550SC.

J. Tyler, 13-JAN-2003; D287400, IMIDACLOPRID; Health Effects Division (HED) 

Metabolism Assessment Review Committee (MARC) Decision Document.

J. Tyler, 3-DEC-2008; D353984, Imidacloprid. Human Health Assessment Scoping Document in 

Support of Registration Review.

J. Tyler; 7-MAR-2013; D400189, Section 3 Requests for Use on Oyster Beds.

J. Tyler; 7-MAR-2013; D400187, Acute and Chronic Aggregate Dietary (Food and Drinking 

Water) Exposure and Risk Assessments for the Section 3 Registration Action for Use on Oyster 

Beds; and the Section 18 Emergency Exemption Request for Use on Sugarcane in Louisiana 

(LA).

J. Tyler, 7-MAR-2013; D407182, Occupational Exposure Assessment to Support a Section 18 

Request for the use of Imidacloprid on Sugarcane in Louisiana.

cc: J. Tyler

RDI: risk assessment team (12/12/12); RAB1 (12/19/12); G. Kramer (12/17/12); C. Smith (12/17/13)

J. Tyler: S-10943: Potomac Yard 1 (PY1): (703) 305-5564: 7509P: RAB1
Imidacloprid Human-Health Risk Assessment DP#s 399719 and 407172

Page 41 of 45

Appendix A. Toxicology Profile and Executive Summaries.

Table A.1. Acute Toxicity of Imidacloprid.

Guideline No. Study Type MRID #(s) Results Toxicity Category

81-1 Acute Oral 42055331 LD50 = 424 mg/kg (M)

LD50 >450 mg/kg (F)

II

81-2 Acute Dermal 42055332 LD50 >5000 mg/kg IV

81-3 Acute Inhalation 42256317 LC50 >5.33 m/L IV

81-4 Primary Eye Irritation 42055334 Not an eye irritant IV

81-5 Primary Skin Irritation 42055335 Not a dermal irritant IV

81-6 Dermal Sensitization 42055336 Not a dermal sensitizer N/A

Table A.2. Toxicity Profile of Imidacloprid Technical.

Guideline No./ Study Type MRID No. (year)/ 

Classification /Doses Results

870.3100

90-Day oral toxicity rodents (rats)

NA NA

870.3150

90-Day oral toxicity (nonrodents)

NA NA

870.3200

21/28-Day dermal toxicity

(rabbits)

42256329 (1990)

Acceptable/guideline

0 or 1000 mg/kg/day 

6 hr/day, 5 d/week

NOAEL = 1000 mg/kg/day (HDT).

LOAEL = not identified.

870.3250

90-Day dermal toxicity

NA NA

870.3465

4-Week inhalation toxicity

(rat)

42273001 (1989) 

Acceptable/guideline

0, 0.0055, 0.035, or 0.191 

mg/L/day, 6 hr/day,

5 d/week for 4 weeks

NOAEL = 0.191 mg/L/day (HDT).

LOAEL = not identified.

870.3700a

Prenatal developmental toxicity 

(rats)

42256338 (1992)

Acceptable/guideline 

F: 0, 10, 30, or 100 

mg/kg/day

Maternal NOAEL = 10 mg/kg/day.

LOAEL = 30 mg/kg/day based on decreased body-weight gain and 

decreased corrected body-weight gain.

Developmental NOAEL = 30 mg/kg/day.

LOAEL = 100 mg/kg/day based on a slight increase in the incidence of 

wavy ribs.

870.3700b

Prenatal developmental toxicity 

(rabbits)

42256339 (1992)

Acceptable/guideline

F: 0, 8, 24, or 72 

mg/kg/day

Maternal NOAEL = 24 mg/kg/day.

LOAEL = 72 mg/kg/day based on maternal deaths and decreased maternal 

absolute body weights, body-weight gains, and food consumption.

Developmental NOAEL = 24 mg/kg/day.

LOAEL = 72 mg/kg/day based on abortion, total litter resorptions, 

increased post-implantation loss due to increased late resorptions, 

decreased fetal weights, and very low incidences of skeletal alterations.

870.3800

Reproduction and fertility effects 

(rats)

42256340 (1990)

Acceptable/guideline

0, 100, 250, or 700 ppm

F0 (M/F): 0, 8.1/8.8, 

20.1/22.1, or 56.7/62.8 

mg/kg/day

F1 (M/F): 0, 6.4/7.2, 

16.5/18.9, or 47.3/52.3 

mg/kg/day

Parental/Systemic NOAEL = 16.5 mg/kg/day.

LOAEL = 47.3 mg/kg/day based on decreased premating weight gain by 

F0 males and females and F1 females and decreased gestational weight 

gain by F1 females.

Reproductive NOAEL = 47.3 mg/kg/day (HDT).

LOAEL = not identified.

Offspring NOAEL = 16.5 mg/kg/day.

LOAEL = 47.3 mg/kg/day based on decreased pup body weights in both 

litters of both generations.

870.4100a

Chronic toxicity (rodents)

NA; see 870.4300 NA

870.4100b

Chronic toxicity (dogs)

42273002 (1989)

Acceptable/guideline

0, 200, 500, or 1250/2500 

ppm

M/F: 0, 6.1, 15, or 41(first 

16 wks.), then 72 mg/kg/d

NOAEL = 72 mg/kg/day (HDT).

LOAEL = not identified.

870.4200a

Carcinogenicity (rats)

NA; see 870.4300 NA

870.4200b 42256335 (1991) NOAEL = Males: 208 mg/kg/day; Females: 274 mg/kg/day.
Imidacloprid Human-Health Risk Assessment DP#s 399719 and 407172

Page 42 of 45

Table A.2. Toxicity Profile of Imidacloprid Technical.

Guideline No./ Study Type MRID No. (year)/ 

Classification /Doses Results

Carcinogenicity (mice) Acceptable/guideline with 

42256336

0, 100, 330, or 1000 ppm

M: 0, 20, 66, or 208 

mg/kg/day

F: 0, 30, 104, or 274 

mg/kg/day

42256336 (1991)

0 or 2000 ppm

M: 0 or 414; F: 0 or 424 

mg/kg/day

LOAEL = Males: 414 mg/kg/day; Females: 424 mg/kg/day based on 

decreased body weights, food consumption and water intake.

No evidence of carcinogenicity.

870.4300

Combined Chronic/carcinogenicity 

(rats)

42256331 (1989)

Acceptable/guideline with 

42256332

0, 100, 300, or 900 ppm

M: 0, 5.7, 16.9, or 51.3 

mg/kg/day

F: 0, 7.6, 24.9, or 73.0 

mg/kg/day

42256332 (1991)

0 or 1800 ppm

M: 0 or 102.6; F: 0 or

143.7 mg/kg/day

NOAEL = Males: 5.7 mg/kg/day; Females: 7.6 mg/kg/day.

LOAEL = Males: 16.9 mg/kg/day; Females: 24.9 mg/kg/day based on 

thyroid toxicity (increased incidence of mineralized particles in thyroid 

colloid) in males.

No evidence of carcinogenicity.

870.5100

Bacterial reverse mutation

42256341

Acceptable/guideline

Negative for inducing reverse mutation in bacteria exposed to doses up to 

5000 ug/plate.

870.5100

Bacterial reverse mutation

42256343

Acceptable/guideline

Negative up to 12,500 ug/plate.

870.5100

Bacterial reverse mutation

42256363

Acceptable/guideline

Negative up to 5500 ug/plate.

870.5300

In vitro mammalian cell gene 

mutation

42256342

Acceptable/guideline

Negative for inducing forward mutation in Chinese Hamster Ovary (CHO) 

(mammalian) cells treated up to 1222 ug/mL.

870.5300

In vitro mammalian cell gene 

mutation

42256364

Acceptable/guideline

Negative up to 2000 ug/mL.

870.5300

In vitro mammalian cell gene 

mutation

42256365

Acceptable/guideline

Negative up to 2000 ug/mL.

870.5375

In vitro mammalian chromosome 

abberation (HL)

42256345

Acceptable/guideline

Positive at 500 ug/mL - S9 and 1300 ug/mL +S9, both cytotoxic doses.

870.5375

In vitro mammalian chromosome 

abberation (CHV79)

42256370

Acceptable/guideline

Negative up to 1000 ug/mL.

870.5375

In vitro mammalian chromosome 

abberation (CHO)

42256371

Acceptable/guideline

Negative up to 1000 ug/mL.

870.5380

Mammalian germ cell chromosome 

abberation (mouse)

42256348

Unacceptable/guideline

Negative, but only tested up to 80 mg/ml.

870.5385

Mammalian bone marrow 

chromosome aberration (chinese 

hamster)

42256344

Acceptable/guideline

Negative for chromosome breakage up to 2000 ug/mL.

870.5395

Mammalian micronucleus (mouse)

42256347

Unacceptable/guideline

Negative, but only tested up to 80 mg/kg.

870.5395

Mammalian micronucleus (mouse)

42256366

Acceptable/guideline

Negative up to 50 mg/kg IP, toxic dose.

870.5395

Mammalian micronucleus (mouse)

42256367

Unacceptable/guideline

Negative up to 80 mg/kg IP, a non-toxic dose.

870.5395

Mammalian micronucleus (mouse)

42256368

Unacceptable/guideline

Negative up to 100 mg/kg PO, a non-toxic dose.

870.5395

Mammalian micronucleus (mouse)

42256369

Acceptable/guideline

Negative up to 160 mg/kg PO, toxic dose.
Imidacloprid Human-Health Risk Assessment DP#s 399719 and 407172

Page 43 of 45

Table A.2. Toxicity Profile of Imidacloprid Technical.

Guideline No./ Study Type MRID No. (year)/ 

Classification /Doses Results

870.5500

DNA damage/repair REC assay

41156351

Acceptable/guideline

Negative up to 5000 ug/disc, the limit of solubility, with or without 

activation.

870.5550

Unscheduled DNA synthesis 

(RPH)

42256352

Acceptable/guideline

Negative up to 750 ug/mL, a cytotoxic dose.

870.5575

Mitotic gene conversion

42256353

Acceptable/guideline

Negative for crossing-over in yeast cells exposed with/without activation 

to precipitating levels of test article (5,000-10,000 ug/mL).

870.5550

Unscheduled DNA synthesis 

(RPH)

42256372

Acceptable/guideline

Negative up to cytotoxic doses (1333 ug/mL).

870.5900

In vitro sister chromatid exchange 

(CHO)

42256349

Acceptable/guideline

Positive at 500 ug/mL -S9 and 2000 ug/mL +S9, both cytotoxic doses.

870.5900

In vitro sister chromatid exchange 

(CHO)

47256350

Acceptable/guideline

Negative at cytotoxic doses of 400 ug/mL -S9 and 1250 ug/mL +S9.

870.59.15

In vivo sister chromatid exchange 

(chinese hamster bone marrow)

42256346

Acceptable/guideline

Negative up to 2000 mg/kg.

870.6200a

Acute neurotoxicity screening 

battery

rat

43170301 (1994)

43285801 (1994)

Acceptable/guideline

0, 42, 151, or 307 mg/kg

NOAEL = not identified.

LOAEL = 42 mg/kg based on decreased motor and locomotor activities 

observed in females.

870.6200b

Subchronic neurotoxicity screening 

battery

rat

43286401 (1994)

Minimum

0, 150, 1000, or 3000 ppm

M: 0, 9.3, 63.3, or 196 

mg/kg/day

F: 0, 10.5, 69.3, or 213 

mg/kg/day

NOAEL = 9.3 mg/kg/day.

LOAEL = 63.3 mg/kg/day based on decreased body-weight gain.

870.6300

Developmental neurotoxicity

(rat)

45537501 (2001)

Acceptable/non-guideline

0, 100, 250, or 750 ppm

Gest.: 0, 8.0-8.3, 19.4-

19.7, or 54.7-58.4 

mg/kg/day

Lact.: 0, 12.8-19.5, 30.0-

45.4, or 80.4-155.0 

mg/kg/day

Maternal NOAEL = 20 mg/kg/day.

LOAEL = 55 mg/kg/day based on decreased food consumption and bodyweight gain during lactation.

Offspring NOAEL = 20 mg/kg/day.

LOAEL = 55 mg/kg/day based on decreased body weight and bodyweight gain, decreased motor activity and decreased caudate/putamen 

width in females.

870.7485

Metabolism and pharmacokinetics

rat

42256354 (1990)

42256356 (1987)

M&F: 1.0 or 20.0 mg/kg 

(labeled) as single oral 

dose or 1.0 mg/kg 

unlabeled orally followed 

by 1.0 mg/kg single oral 

dose (labeled) or 1.0 

mg/kg (labeled) single 

dose IV.

M: 20.0 mg/kg single 

oral dose or 1.0 mg/kg 

single duodenal dose.

42256357 (1991)

M&F: 1.0 mg/kg single 

oral dose.

M: 1.0 or 150 mg/kg 

single oral dose

42256373 (1990).

M: 1.0 or 150 mg/kg 

single oral dose or

80.0 mg/kg single oral 

dose after 1 year 1800 

ppm.

42256355 (1987)

M: 1.0 mg/kg single oral 

Methylene-labeled imidacloprid was rapidly absorbed with approximately 

90% of the administered dose being eliminated within 24 hours and 96% 

within 48 hours. There were no biologically significant differences 

between sexes, dose levels, or route of administration. Urinary excretion 

was the major route of elimination (70-80% of recovered radioactivity), 

with a lesser amount eliminated in feces (17-25% of recovered 

radioactivity). Biliary excretion was a major contributor to fecal 

radioactivity (36.6% vs. 4.8% of recovered radioactivity in bile-fistulated 

animals). Total tissue burden after 48 hours accounted for only 

approximately 0.5% of the recovered radioactivity, with major sites of 

accumulation being the liver, kidney, lung, skin, and plasma and minor 

sites being the brain and testes. Maximum plasma concentration occurred 

between 1.1 and 2.5 hours, and elimination half-lives (calculated from two 

exponential terms) were 3 and 26-118 hours. There were two major 

evident routes of biotransformation. The first included an oxidative 

cleavage of the parent compound to give 6-CNA and its glycine conjugate. 

Dechlorination of this metabolite formed the 6-hydroxynicotinic acid and 

its mercapturic acid derivative. The second included the hydroxylation of 

imidazolidine followed by elimination of water of the parent compound to 

give NTN 35884.

In a comparison between [methylene14C]imidacloprid and [imidazolidine4,5-

14C]imidacloprid, the rates of excretion were similar; however, the 

renal portion was higher with the imidazolidine-labeled test material. The 

imidazolidine-labeled test material also demonstrated higher accumulation 

in the tissues, with the major sites of accumulation being the liver, kidney, 
Imidacloprid Human-Health Risk Assessment DP#s 399719 and 407172

Page 44 of 45

Table A.2. Toxicity Profile of Imidacloprid Technical.

Guideline No./ Study Type MRID No. (year)/ 

Classification /Doses Results

or IV dose.

42256358 (1990)

42256359 (1990)

Acceptable/guideline

lung, and skin, and the minor sites being brain and muscle. 

In a comparison between [methylene14C]imidacloprid and WAK 3839, 

there were no significant differences in the absorption, distribution, and 

excretion of the total radioactivity. More radioactivity was found in the 

tissues of the animals receiving imidacloprid at the 1.0 and 150.0 dose 

levels. The major sites of accumulation of WAK 3839 included lung, 

renal fat, liver, and kidney, with minor sites being the testis and brain. 

WAK 3839 was formed during pretreatment (chronic oral dosing) of 

imidacloprid; however, the proposed metabolic pathways of the two 

compounds were different.

870.7600

Dermal penetration

NA NA
Imidacloprid Human-Health Risk Assessment DP#s 399719 and 407172

Page 45 of 45

Appendix B. Physical/Chemical Properties.

Table B1. Physicochemical Properties of Imidacloprid.

Parameter Value Reference

Molecular Weight 255.7

PP#6E7116;

W. Cutchin, 14-May-2007; DP#s: 

332757, 333517, & 334153

The Pesticide Manual

Twelfth Edition (2000)

pH 5 to 11

Water solubility (g/L at 23°C) 1.54

Solvent solubility (g/L at 20°C)

Dichloromethane: 55, 

Isopropanol: 1.2, 

Toluene: 0.68, n-hexane: 

<0.1

Vapor pressure (mPa at 20°C) 4 x 10-7

Octanol/water partition coefficient, log KOW

(25°C) 0.57 (21°C)

Henry’s law constant (@20°C) 6.5x10-11 atm m3/mole Cal-EPA

Soil Half-life (or other relevant information from 

EFED Drinking water assessment)

R.Parker, 13-April-2007; DP#s: 

334029, 334030, 332756, 333122, 

333123,

333125, 333126, 330568, 330569

Hydrolysis half-life @ pH 7 Stable

Photolysis half-life, distilled water (days) 0.2

Photolysis half-life, soil (days) 39

Aerobic soil half-life (days) 359

Aerobic aquatic metabolism half-life (days) 27

Soil leaching (KOC, mL/g) 178 (132-256)