Page 3 of 29

In con junction with HED ’s conclusion that the 21/28 day inhalation study is required to support registration review, HED retained the 10X uncertainty factor for the inhalation route of exposure
in its most recent new use risk assessment. ( E. Holman et al ., 04/19/2012 ). During registration review, the endpoints, doses, and safety factors used in the most recent human health risk

assessment s should be reconsidered based on current HED policy , as well as any new data
received.

The current e ndpoi nt selection for acute dietary and short

- and intermediate t erm incidental oral, dermal, and inhalation assessments are based on the point of departure (POD) and endpoints (i.e., body weight changes, decreased pup survival

, and decreased startle response) from the developmental neurotoxicity study in rats. Chronic dietary and long

- term dermal and inhalation
assessments are based on the body weight changes and liver effects ( hepatocellular vacuolation )
observed in the combined chronic/carcinogenicity study in rats.

T he dietary exposure database is adequate to support the registration review of acetamiprid

. However, if the acute and chronic dietary endpoints change, an updated dietary risk assessment

may be needed. Any updated dietary assessment would include any upd ated drinking water
estimates

. Currently, the re are no dietary risk estimates of concern for the existing uses of acetamiprid

.

The residential exposure database is adequate to support registration review for acetamiprid . A ll of the residential handler and postapplication risk estimates are below the Agency’s level of

concern. An updated residential exposure assessment may be needed during registration review as a result of the revisions to HED’s Residential Exposure Standa rd Operating Procedures (SOPs). Furthermore, because of the potential for residential bystander exposure to acetamiprid
from aerial and airblast applications, volatilization, and/or transport from treated areas (drift)

, HED will evaluate the need for a by stander assessment during registration review.

For acetamiprid , residential exposures are aggregated with dietary exposures. In the most recent
human health risk assessment, the re were no aggregate risk estimates of concern (Memo,
D3 94322

, E. Holman et a l ., 04/19/2012 )

. During registration review, updated aggregate risk

assessments may be needed

.

The occupational exposure database is adequate to support registration review for acetamiprid

. There are no occupational handler and postapplication risk estimates of concern. Although no
chemical

- specific dislodgeable foliar residue (DFR) data are available, these data are not required for the current uses based on weight of evidence considerations. This conclusion may change if new uses and/or higher ap plication rates are proposed. HED will consider the need for

a n updated occupational exposure assessment d ur ing registration review , pending the receipt of the inhalation toxicity study; until the data from that study are reviewed, and regulatory determinations based on that review are implemented

, interim mitigation may be needed to
ensure inhalation exposure s are not of concern

. These interim mitigation measures will need to
be considered particularly for handlers mixing/loading acetamiprid formu lations for aerial application, or multiple activities workers conducting seed treatments , as these scenarios are where inhalation exposure is anticipated to be greatest

.Page 4 of 29

Introduction

HED evaluated the most recent human health risk assessments for acetam iprid in associ ation
with the available toxicity, exposure, and usage information to determine if sufficient data are available and if further updates are needed to support registration review. Recent human health
risk assessments include a 20 12 assessmen t for the use of acetamiprid on asparagus , leafy greens, turnip greens, and sweet corn (Memo, D394322, E. Holman et al

., 04/19 / 2012 ) and the 2011 assessment for the use of acetamiprid in food handling establishments and on soybean (Memo,

D 385260, M . Doherty et al. , 11 / 30 /20 11 ). In addition, HED considered the latest Agency science policies and risk assessment methodologies.

The structur e of acetamiprid , as well as the chemical names and other identifiers can be found in the chemical identity tab le attached to this document (Attachment 1)

.

Acetamiprid is registered for use on a wide variety of crops, and permanent tolerances have been established (40 CFR §180.578) ranging from 0.01 ppm to 50 ppm in plant commodities and from 0.010 ppm to 0.20 ppm in livestock commodities. These tolerances are summarized in
Attachment 2 , along with International Residue Limits

. Acceptable analytical methods are available to enforce tolerances for residues of acetamiprid in plant and livestock commodities.

The re gistered formulations, active ingredient levels, use sites, application methods, and uses that
were evaluated in previous assessments a re summarized in Attachment 3

.

Hazard Identification/ Toxicology

The toxicology database for acetamiprid is mostly complete, with the exception of a 28 day subchronic inhalation toxicity study, which is a required study. HED has determined that the required inhalation study cannot be waived, based on weight of evidence considerations, including the available toxicity data and the potential for exposure to acetamiprid via the
inhalation route.

In all species tested, generalized nonspecific toxicity was observed as decreases in body weight, body weight gain, food consum ption and food efficiency. Generalized effects were also observed in the liver in the form of hepatocellular hypertrophy in both mice and rats and hepatocellular vacuolation in the rat. These effects were considered to be adaptive. Other
effects observe d in the oral studies include amyloidosis of multiple organs in the mouse oncogenicity study, tremors in high dose females in the mouse subchronic study, and microconcretions in the kidney papilla and mammary hyperplasia in the rat chronic/oncogenicity

stu dy.

In an acute rat neurotoxicity study, a decrease in locomotor activity was observed in both sexes on the day of dosing. A slight decrease in the duration of movements persisted in some males during later observations . Functional observational battery evaluations revealed several

treatment

- related observations on the day of dosing. At the high dose only, males exhibited tremors, difficulty in handling, walking on toes, dilated pupils, coldness to the touch

, as well as decreased forelimb grip strength and hind limb foot splay. High

- dose females displayed tremors,Page 5 of 29

chewing, coldness to the touch, dilated pupils, decreased hind limb foot splay, and abnormal gaits and/or posture, including walking on toes and hunched posture. This was not noted in a
subchr onic rat neurotoxicity study. No neuropathology was observed in any of the neurotoxicity studies. Tremors in high dose female mice in the subchronic feeding study were the only other potentially neurotoxic effects observed in any other studies.

Four week immunotoxicity studies were performed in both sexes in rats and mice. No effects on the immune system were observed in either species up to the highest dose tested . Significant reductions in body weight and body weight gain were noted at that d ose.

No effects were observed in the 21

- day dermal study in the rabbit

. A dermal absorption study with acetamiprid was conducted using male rats with exposure durations up to 24 hours. In some earlier acetamiprid risk assessments, a 30% dermal absorption value was estimated from this study. However, for more recent assessme nts, HED determined that a refined dermal penetration value for acetamiprid of 10% is reasonable and protective after reexamining the acetamiprid dermal penetration study and reviewing the dermal penetration information for
several other neonicotinoid inse cticides

. No inhalation toxicity studies were conducted.

There was no quantitative or qualitative evidence of increased susceptibility of rat or rabbit
fetuses to in utero exposure in the developmental studies. However, increased qualitative susceptib ility was observed in a 2

- generation reproduction study and a developmental neurotoxicity , both in rats. In the reproduction study, decreased body weight, body weight gain, and food consumption were observed in parental animals while significant reduction s in pup weights were seen in the offspring in both generations. Also observed were reduction in litter size, and viability and weaning indices among F 2 offspring as well as significant delays in the age to attain vaginal opening and preputial separation. In the DNT study, parental effects were limited to decreased body weight and body weight gains, while the offspring effects noted were decreased body weights and body weight gains, decreased pre

- weaning survival (post

- natal days (PNDs) 0

- 1), and decrease d maximum auditory startle response in males on PNDs 20 and 60

.

Despite the increase in qualitative susceptibility observed in rats, HED recommended that the FQPA SF of 10X be reduced to 1X for dermal and oral exposure pathways based on the following reasons: (1) the toxicology data base is complete (with the exception of an inhalation study); (2) HED is regulating the use of acetamiprid based upon the effects of concern, i.e., developmental effects in pups following pre

- and/or post

- natal exposure; ( 3) the rat is the most sensitive species tested, and the NOAEL and LOAEL selected from the DNT study in rats are protective of effects observed in other species throughout the toxicology database; ( 4 ) there are no residual uncertainties for pre

- and/or post

- natal toxicity; ( 5) the exposure databases (dietary food, drinking water, and residential) are complete; and ( 6) the risk assessment for each potential exposure scenario includes all metabolite s and/or degradates of concern and does not underestimate the potential risk to infants or children.

However, i n the absence of the required inhalation toxicity study, HED recommen ded that the 10X FQPA factor be retained as a database uncertainty factor for assessing exposure and risk via
the inhalation route

.Page 6 of 29

Acetamiprid is classified as “not likely to be carcinogenic to humans.” The classification is based on (1) the absence of an increase in the incidence of tumors in a mouse carcinogenicity study; and (2) in a rat chronic/carcinogenicity study, the absence of a dose

- response and the lack of a statistically significant increase in the mammary adenocarcinoma incidence by pair

- wise comparison of the mid

- and high

- dose groups with the controls (althoug h the incidence exceeded the historical control data from the same laboratory, it was within the range of values from the supplier). There was no clear evidence of a mutagenic effect. Acetamiprid tested positive as a clastogen in an in vitro study but not in an in vivo study.

Acute lethality studies conducted with acetamiprid indicate d that it is moderately toxic via the

acute oral route (Category II); however, it has low toxicity via the acute dermal or inhalation routes (Categories III). It is non

- irri tating to the eyes and skin and is not a dermal sensitizer.

In the most recent human health risk assessment for acetamiprid (E. Holman, D394322) , the endpoint selection for acute dietary, short

- and intermediate term incidental oral, dermal, and
inhalation assessments are based on the POD and endpoints from the developmental neurotoxicity study in rats. Chronic dietary and long

- term dermal and inhalation assessments are
based on the body weight changes and liver effects ( hepatocellular vacuolation ) observed in the combined chronic/carcinogenicity study in rats.

Conclusions for Hazard Identification/Toxicology

The toxicology database for acetamiprid is mostly complete. However, a 28 day inhalation toxicity study is not available. This study is required based on weight of evidence considerations, including the available toxicity data and the potential for exposure to acetamiprid
via the inhalation route. This data gap was identified in a recent new use registration risk assessment ( Memo, D394322, E. Holman et al ., 04/19/2012 ). T here is uncertainty about potential portal of entry effects occurring via th e inhalation route of exposure. Therefore, in the absence of the study, HED has retained the 10X FQPA factor as a database uncertainty factor for the inhalation route of exposure only, pending submission of the required study. The selected toxicological endpoints from the most recent human health risk assessment are summarized in
Attachment 4

.

During registration review, the endpoints, doses, an d safety factors used in the most recent
human health risk assessment s should be reconsidered based on current HED policy , as well as any new data receive d

.

Dietary Exposure

As stated above, acetamiprid is registered for use on a wide variety of crops , and permanent tolerances have been established (40 CFR §180.578) ranging from 0.01 ppm to 50 ppm in plant commodities and from 0.010 ppm to 0.20 ppm in livestock commodities. The residue definition for risk assessment and tolerance enforcement is the pa rent compound for plant commodities, and combined residues of the parent compound and Metabolite IM

- 2

- 1 for livestock commodities (plus Metabolite IM

- 2

- 1

- amide in ruminant muscle for risk assessment purposesPage 7 of 29

only). Acceptable analytical methods are availa ble to enforce tolerances for residues of acetamiprid in plant and livestock commodities.

HED used the Dietary Exposure Evaluation Model (DEEM

- FCIDTM Version 2.03) to conduct the

most recent acute and chronic aggregate dietary (food and drinking water ) ris k assessments for acetamiprid . This model incorporate s consumption data from the USDA’s Continuing Survey of Food Intakes by Individuals taken between 19 94 and 199 6 along with a supplemental children’s survey taken in 1998. Both the acute and chronic ana lyses are based on tolerance

- level residues, assume 100% crop treated, and utilize both empirical and default processing factors. In order to estimate food handling establishment residues in the chronic analysis, a residue value of 0.01 ppm has been used for all food forms not already accounted for by existing/proposed uses. Note that per HED policy, residue estimates associated with the food

- handling establishment uses are not included in the acute dietary assessment.

The most recent acute dietary exposure resulted in an estimated risk equivalent to 21% of the aPAD (acute population adjusted dose) for the general U.S. population at the 9 5 th percentile of exposure. The most highly exposed population subgroup was C hildren 1

- 2 years old

, which u sed
5 2 % of the aPAD at the 9 5 th percentile of exposure

. C hronic dietary exposure to acetamiprid resulted in an estimated risk equivalent to 1 0 % of the cPAD (chronic population adjusted dose) for the general U.S. population. The most highly expose d population subgroup was Children 1

- 2

, which used 3 3 % of the cPAD.

EFED recommended that model ed estimates of residues in drinking water be used in the most recent dietary risk assessment. During registration review, HED will evaluate whether updated drinking water estimates are available and whether these revised estimates make it necessary to complete a new dietary assessment. Depending on the magnitude of any updates, a new dietary

asses sment may be required to appropriately estimate risks associated with drinking water

exposure.

Conclusions for Dietary Exposure

The dietary exposure database is adequate to support the existing registrations and tolerances

. No new residue chemistry d ata are required. However, a new dietary assessment may be needed if one or more of the following occur: new data are identified which impact dietary exposure estimates, including those from drinking water; new toxicological points of departure are
identi fied, including revisions to the FQPA SF; Office of Pesticide Programs ( OPP ) dietary exposure policies and procedures are revised. HED is in the process of updating its dietary
model to incorporate more recent consumption data from the National Health an d Nutrition Examination Survey (NHANES)

. Th e new er version of the model will be used during registration review if a new dietary assessment is needed.

Residential Expo s u re

Acetamiprid is registered for controlling a number of indoor and outdoor household and ornamental insect pests in residential settings , but t here are no registered turf uses. Some of the acetamiprid products are formulated, packaged, and registered for use by homeowners and theyPage 8 of 29

include baits and bait stations, WSP, ECs, and re ady

- to

- use (RTU) sprays. The most recent residential exposure assessment s also included structural insect control products that are designed for use by commercial and professional applicators. Unless these products are labeled for “Restricted Use Only” t h ey are assumed to be available for purchase and use by homeowners

, resulting in residential handler exposures. The recommended application equipment for
household and commercial labels includes hose

- end sprayers , manually pressurized handwands,
and eithe r pump or electric hand

- held sprayers. The cockroach baits and fly strips are applied by
hand

, but very little homeowner exposure is expected due to lack of dermal contact and vapor generation. A cetamiprid use s in both indoor and outdoor areas r esult in short

- (1

- 30 days) and
intermediate

- term (1

- 6 months) exposures for residential handlers. For handler exposure via the dermal route, and postapplication exposure via the dermal and oral routes

, HED ’s level of concern (L OC ) is 100 , and therefore if the est imated margin of exposure ( MOE ) is ≥ 100, the risk
is not of concern. However, for inhalation exposures, an additional 10X factor was retained for the missing inhalation toxicity study, and therefore the LOC for inhalation exposure is an MOE
of 1000.

Resi dential Handler Exposure

Most of the residential uses of acetamiprid have been evaluated for residential handler exposures (Attachment 3). There were no risks of concern identified for the assessed residential handler
scenarios. S ome s cenarios corresponding to registered uses of acetamiprid have not been assessed quantitatively at this time for residential handler risks

-- these scenarios are either similar

to scenarios assessed previously that did not sho w risks of concern or they repre sent potentially lower exposure s; we consider the risks associated with th e se scenarios not to be of concern. During registration review, HED will reassess representative residential handler scenarios, taking into account any new information such as revi sed toxicological endpoints and uncertainty factors
for risk assessment.

Recently, HED has updated the Residential Standard Operating Occupational Pesticide Handler Unit Exposure (OPHED) Surrogate Data (June 21, 2011) and Human Body weight Data ; therefo re , new assessments may be required during registration review to update the risk
estimates

.

Residential Postapplication Exposure

Use of structural insect control products containing acetamiprid in indoor and outdoor settings by homeowners and professional applicators results in short

- and intermediate

- term postapplication dermal and inhalation exposure to adults and children

, and in cidental oral exposure to children.

No postapplication dermal exposure to acetamiprid is anticipated for either adults or children following the use of cockroach/ant baits and fly strips in homes , due to the way these products are packaged and applied. Use of acetamiprid as crack and crevice, mattress

, and outdoor perimeter treatments result s in estimated dermal MOEs of ≥300 for adults and children

, and
incidental oral MOEs ≥900 for children ; since all assessed dermal and oral postapplication
scenarios r esulted in MOEs greater than the LOC of 100, the risk estimates are not of concern.Page 9 of 29

Postapplication i nhalation exposure to adults and children may occur by breathing indoor air after surface and crack and crevice treatments with acetamiprid sprays. Pest icide vapor may be produced from surface applications and by vaporization of the active ingredient. A Tier 1 (Air Saturation Concentration) analysis of the indoor uses indicated that the exposure and risk
resulted in MOEs significantly greater than 100 (t he inhalation LOC at the time) and we re therefore not of concern ( M. Collantes, D383325, 7/22/201 1). In addition, HED recently update d the exposure and risk estimates via the inhalation route ; relative to the new LOC of 1000 for inhalation exposure, the r isks were not of concern (MOEs ≥ 1000)

.

R esidential bystander exposures to acetamiprid may result from the off

- site transport of spray droplets applied to agricultural sites and for public health insect control. Pesticide drift to nearby
residential areas may be more typically associated with aerial application s , but it could also be a potential source of exposure from ground

- based application s of acetamiprid. The Agency has been working with the Spray Drift Task Force, EPA Regional Offices

, and Sta te Lead Agencies for pesticide regulation and other parties to develop the best spray drift management practices (see the Agency’s Spray Drift website for more information at http://www.epa.gov/opp00001/factsheets/spraydrift.htm . On a chemical

- by

- chemical basis, the Agency may requir e specific mitigation measures to address pesticide drift

. Other potential

sources of residential bystander postapplication exposure include volatilization of pesticides and

re

- suspension of dusts and/or particulates that cont ain pesticides.

Although a quantitative residential bystander postapplication inhalation exposure assessment was not performed for pesticide drift from treated agricultural fields, an inhalation exposure assessment was performed for flaggers who assist in aerial applications of acetamiprid at 0.039 lb ai/A on soybean fields resulted in an MOE of 8,800 ( not of concern based on the LOC of 100 0 for inhalation exposure ) . The flagger scenario is considered to be representative of a worst case inhalation (drift ) exposure (S. Oonnithan, D389062, 11/16/2011) , thus all other inhalation drift exposures are not considered to pose risks of concern

.

Combined Residential Exposure

HED combines residential handler and postapplication exposures for adults

, and combines postapplication exposures for children

, resulting from residential exposure scenarios when it is likely they can occur simultaneously based on the use

- pattern and the behavior associated with the exposed population . Such an analysis performed for all res idential uses of acetamiprid indicated combined postapplication MOEs of 430 for adults and 220 for children . T he combined
MOEs are greater than 100

, so these combined exposures are not considered to be of concern (M. Collantes, D383325, 7/22, 2011). Derm al, oral, and inhalation risks for short

- term exposures were combined in the most recent risk assessment, since the toxicological endpoints were the

same for the relevant routes of exposure ( Memo, D394322, E. Holman et al ., 04/19/2012 )

. However, the leve l of concern (LOC) values were different (i.e. dermal and oral LOC = 100, while inhalation LOC = 1000); therefore, the respective risk estimates we re combined using the aggregate risk i n dex (ARI) approach . I n HED’s most recent risk assessment, residential exposure and risk were recalculated using th e ARI) approach to account for the new LOC of 1000 for inhalation exposures, and there were no combined risks of concern (i.e., ARI>1).Page 10 of 29

Conclusions for Residential Exposure

All residential handler (adults) an d postapplication exposure scenarios (children and adults)
resulted in dermal and oral MOEs greater than the LOC of 100 and are not of concern. Even when the revised LOC of 1000 is considered for the inhalation route of exposure, there are no
risks of con cern identified. For these assessments, HED used default assumptions from the Residential Standard Operating Procedures (SOP), April 5, 2000. However, as a result of the recent revisions made to HED’s Residential SOPs, the parameters and algorithms for d ermal, inhalation, and oral exposure calculations will likely change. These changes could result in a different residential handler/postapplication exposure estimates and therefore, during registration review, HED may conduct a new residential exposure assessment that incorporates any potential new methods or policies for estimating exposure associated with residential use patterns. Furthermore, residential bystander exposures might occur as a result of aerial application if acetamiprid , volatilization of active ingredient from treated surfaces , and/or transport from treated areas. HED will evaluate the need for a bystander assessment during registration review. Additionally, refinements to residential inhalation exposure assessments may be required d uring registration review when the 28

- day inhalation study is submitted per the Hazard and Science Policy Council ( HASPOC ) recommendations and a route endpoint and dose are selected.

Aggregate Risk Assessment

In the most recent risk assessment (Memo, D3 9 4322

, E. Holman

, 04 / 19 / 2012 ), a ggregate risk

assessment s for acetamiprid exposures were conducted as follows: acute and chronic aggregate assessments were conducted based on food and water exposures, and short

- t erm aggregate assessments were conducted base d on food, water, and residential exposures. No long

- term aggregate risk assessment w as conducted because no long

- term exposure scenarios are expected
from residential uses of acetamiprid

. There were no aggregate risk estimate s of concern associated with the existing uses

.

Conclusions for Aggregate Assessment

During registration review, updated aggregate assessments may be conducted to include changes in toxicological endpoints

, updated dietary exposure estimates, and updated residential exposure estimates. However, these updates may occur in conjunction with new use risk assessments, and therefore would not be needed during registration review.

Occupational Exposure and Risk

Sec tion 3 and Sec tion 24 (c) registrations of acetamiprid are listed in Attachment 3. These formulations may be applied using aerial, groundboom, airblast, and handheld spray equipment. For seed treatment, on

- farm and commercial treatment methods may be used. The personal protective equipment ( P PE) required for handlers and is single layer clothing (long sleeve shirt, long pants, and socks plus shoes) and chemical resistant gloves. For seed treatment, PPE consists of single layer clothing, chemical resistant gloves and dust/mist respirator. The restricted entry interval (REI) for acetamiprid formulations is 12 hours.Page 11 of 29

The agricultural, ornamental, and structural pest control uses of acetamiprid result in short

- term (1

- 30 days) and intermediate

- term (1

- 6 months) occupational exposures. For e valuating occupational handler and postapplication risks resulting from use of acetamiprid, the Health Effects Division ( HED ) has set a level of concern (LOC) of 100 for the dermal route and 1000 for the inhalation route; when estimated MOE s exceed these LOCs for the respective routes of exposure, the MOEs are not of concern (i.e., ≥100 for dermal and ≥1000 for inhalation)

.
Occupational Handler Exposure

The registrant has not submitted chemical

- specific exposure data to estimate handler expo sures. In the absence of chemical

- specific data, i t is HED policy to use the best available data to assess handler exposure s . Sources of such generic (surrogate) handler data include Pesticide Handlers Exposure Database Version 1.1 (PHED 1.1), and the Ag ricultural Handler Exposure Task Force (AHETF) 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 Federal Insecticide, Fungicide, a nd Rodenticide Act ( FIFRA ) . Default assumptions established by the

HED 's Exposure Science Advisory Council for Exposure (ExpoSAC) were used for parameters such as body weight, acres treated per day and amount of active ingredient handled per day

.

Most of the handler exposures resulting from a gricultural , structural

, and seed treatment use s of acetamiprid have been evaluated (Attachment 3). All the estimated dermal risks resulted in MOEs greater than 100 either at baseline (single layer clothing) or wit h additional PPE (i.e., gloves and/or dust

- mist respirator or engineering controls). For exposure scenarios that have not previously been assessed, they are believed to be similar to those already assessed and therefore

are not likely to pose risks of con cern; these exposure scenarios will be considered during registration review as appropriate

.

However, an additional 10x database uncertainty factor has been retained f or inhalation risk assessments (only) due to the absence of an inhalation toxicity study, as recommended by the HASPOC (TXR 52354, 3/15/2012). Therefore, for inhalation exposure the LOC is an MOE of
1000 ; based on the previous assessments for use of aceta miprid in aerial applications to stone
fruits and seed treatment of canola and mustard

, additional inhalation mitigation measures may be needed, including additional PPE or reduced application rates

.

A few new formulations and/or new uses may have been r egistered without occupational exposure assessment and these will be assessed during registration review. A quick evaluation
of the se previously unassessed scenarios indicate that previously completed assessments would be protective because the uses to be assessed either have lower application rates and/or formulations types that have lower exposure potential. HED has also updated the Occupational Pesticide Handler Unit Exposure (OPHED) Database (June 21, 2011) resulting in small
variations in MOEs from t hose previously estimated , and HED will consider the need for reassessing these scenarios during registration review

.

Occupational Postapplication ExposurePage 12 of 29

Use of acetamiprid on agricultural crop s , for seed treatment, and for structural insect control

re sult s in potential postapplication dermal and inhalation e xposure s to workers when they enter treated areas to perform crop/site specific post

- treatment activities

. The registrant did not submit

a c hemical specific postapplication exposure study for a qua ntitative evaluation of risks resulting from use of registered acetamiprid products. Dermal exposures during postapplication activities were estimated using standard default values for dermal transfer coefficients from the Science Advisory Council for Exp osure Policy Number 3.2: Agricultural Transfer Coefficients, June 3, 2011 and based on proprietary data (from the Agricultural Reentry Task Force [ARTF]) and non

proprietary data. All the estimated dermal risks for agricultural and commercial postapplication
scenarios are not of concern if workers enter treated area s after the REI period of 12 hours has expired. HED is not requesting a chemical

- specific dislodgeable foliar re sidue (DFR) study for acetamip r i d at this time because of the followi ng: 1) No toxicity was observed up to the limit dose tested in the acetamiprid dermal toxicity study; 2) The dermal toxicity endpoint has been conservatively estimated using results from the oral developmental neurotoxicity study; 3) A dermal absorption fa ctor has been derived using a combination of chemical

- specific data and data from structurally similar chemicals , but is still considered to provide an upper

- bound estimate of absorption ; 4) No risks of concern have been identified for postapplication expo sures using these conservative assumptions. If the foliar application use pattern were to change prior to the preliminary risk assessment for registration review , including new uses and/or increased application rates, the registrant should consider submit ting a DFR study.

A quantitative postapplication inhalation exposure as sessment was not performed for acetamiprid
b ased on the Agency's current practices

. However, there are multiple potential sources of inhalation exposure to workers performing postappl ication activities in previously treated fields. These potential sources include volatilization of pesticides and re

- suspension of dusts and/or particulates that contain pesticides. The Agency sought expert advice and input on issues related
to volatiliza tion of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act 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
A gency is in the process of evaluating the SAP report as well as available postapplication inhalation exposure data generated by the Agricultural Reentry Task Force and may, as appropriate, develop policies and procedures, to identify the need for and, subs equently, the way to incorporate occupational postapplication 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 postapplication inhalat ion exposure assessment for acetamiprid.

Although a quantitative postapplication inhalation exposure assessment was not performed for acetamiprid, an inhalation exposure assessment was performed for occupational handlers. Exposure to mixers, loaders, app licators, and flaggers resulting from handling of pesticides for agricultural and structural pest control uses is likely to result in higher inhalation exposure than routine postapplication exposures encountered by workers. The assessment of occupational handler exposure results in MOE s greater than or equal to the LOC (MOE s ≥ 100 0 ) ; these

exposures are considered not to be of concern

. Since inhalation postapplication exposure s are expected to be lower than occupational handler inhalation exposures, we c an infer that th ose risks also are not of concern

.Page 13 of 29

Conclusions for Occupational Exposure and Risk

T he registered uses of acetamiprid have been assessed for occupational handler and postapplication exposure scenarios using the 1998 version of PHED and 2004 version of Seed
Treatment SOPs 14 and 15 (2004). All assessed handler exposure scenarios resulted in dermal MOEs greater than 100 either at baseline or with the addition al PPE such as gloves or mitigation.
All of the estimated dermal risks for post application scenarios are not of concern if workers enter
treated area after the REI period of 12 hours.

Inhalation exposure and risk estimates may be of concern for certain handler scenarios

, including seed treatments, based on the inhalation MOE of 10 00. The results of the requested inhalation toxicity study may impact these conclusions . The need for mitigation of these scenarios will be considered during registration review, and pending receipt of the new study.

During registration review, revise d occupational handler and postapplication assessments may be required if there are any new exposure scenarios or toxicological endpoints

, or if the Agency receives new data that impact dermal or inhalation exposure estimates. In addition, updated
occupat ional handler exposure assessments might be required based upon revisions to the Agency’s scenario

- specific surrogate handler exposure data ( http://www.epa.gov/pesticides/scienc e/handler

- exposure

- table.pdf ). Updated occupational postapplication exposure assessments might also be required under registration review based on revisions to the dermal transfer coefficients from the Science Advisory Council for Exposure Policy Number 3 ( http://www.epa.gov/pesticides/science/ exposac_policy3.pdf ).

Public Health and Pesticide Epidemiology Data

D401173, S. Recore, May 3, 2012

For this evaluation, the OPP Incident Data System (IDS) was utilized to retrieve pesticide incident data on the active ingredient acetamiprid (PC Code 099050). Main IDS incidents involving only one pesticide are considered to provide more certain information about the potential effec ts of exposure from the pesticide. When an incident involves more than one pesticide, it is difficult to determine which effects are attributed to the pesticide being
considered. The less severe human incidents (minor, unknown, or no effects outcomes) are reported by registrants as counts called aggregate summaries and are recorded in a separate module called Aggregate IDS.

For the main IDS, from January 1, 200 7 to February 22, 2012, there were 13 incidents reported involving for the single chemical only in the database and 10 more incidents reported that involved more than one chemical. All of the single chemical incidents were classified as moderate severity. Overall, there are few incidents involving acetamiprid reported to IDS.

In A ggregate IDS , fro m January 1, 200 7 to February 22, 2012, there were 79 reported incident s involving acetamiprid

.Page 14 of 29

Acetamiprid is not included in the Agricultural Health Survey ( AHS ) , and therefore does not provide information for this report.

Based on the low frequency and generally low severity of incident cases reported for acetamiprid , there does not appear to be a concern at this time that would warrant further investigation. The Agency will continue to monitor the incident information and if a concern is triggered, additional analysis will be included in the risk assessment.

Tolerance Assessment and International Harmonization

As stated above, acetamiprid is registered for use on a wide variety of crops and permanent
tolerances have been established (40 CFR §180.578) ranging from 0.01 ppm to 50 ppm in plant commodities and from 0.010 ppm to 0.20 ppm in livestock commodities. The residue definition for risk assessment and tolerance enforcement is the parent compound for plant commodities, and combined residues of the parent compound and Metabolite IM

- 2

- 1 for livestock commodities (plus Metabolite IM

- 2

- 1

- amide in ruminant muscle for risk assessment purposes only). Acceptable analytical methods are available to enforce tolerances for residue s of acetamiprid in plant and livestock commodities. The current tolerance definition for acetamiprid (40 CFR 180.578) is appropriate regarding scope and compliance.

Codex has established maximum residue limits ( MRLs ) for acetamiprid, defined as the pa rent compound for plant commodities, and combined residues of the parent compound and
Metabolite IM

- 2

- 1 for livestock commodities

.

For acetamiprid , Mexico adopts U.S. tolerances and/or Codex MRLs for its export purposes.
Canada has established MRLs for acetamiprid, using the same residue definition as the U.S. and
Codex

. The Canadian MRLs are equivalent to the U.S. tolerances, with only a few exceptions. Specifically, Canadian MRLs are lower for bushberry subgroup 13

- 07B, grapes, and stone fruit,
wher eas they are higher for gooseberries and meat byproducts). For plant commodities, in most cases, the Codex MRLs generally differ from the Canadian and U.S. tolerances, with some values higher and some lower. For livestock commodities, the Codex MRLs are either equal or
lower than the U.S. tolerances.

The international residue limit status sheet can be found in Attachment 2

.

During registration review, HED will reconsider the U.S. tolerances and will harmonize them
with Codex MRLs to the extent possi ble

.

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 variet y of consumer subgroups according to well

- established procedures. In line with OPP policy, HED estimates risks to population subgroups fromPage 15 of 29

pesticide exposures that are based on patterns of that subgroup’s food and water consumption,
and activities in and around the home that involve pesticide use in a residential setting. Extensive data on food consumption patterns are compiled by the USDA under the Continuing Survey of Food Intake by Individuals (CSFII) and are used in pesticide risk assessments for all registered food uses of a pesticide. These data are analyzed and categorized by subgroups based on age, season of the year, ethnic group, and region of the country. Additionally, OPP is able to assess dietary exposure to smaller, specialized subgroups a nd exposure assessments are performed when conditions or circumstances warrant. Whenever appropriate, non

- dietary

exposures and risks based on home use of pesticide products for adult applicators and postapplication activities for toddlers, youths, and ad ults entering or playing on treated areas 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 w orkers as well as lifestyle and traditional dietary patterns among specific subgroups.

Endocrine Disruptor Screening Program

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse outcomes from exposure to chemicals. C ollectively, these studies include acute, subchronic and chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include endpoints which may be susceptible to e ndocrine influence, including effects on endocrine target organ histopathology, organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluate s acute tests and chronic studies that assess growth, developmental and reproductive effects in different taxonomic groups. As part of acetamiprid ’ s most recent registration decision, EPA reviewed these data and selected the most sensitive endpoints for r elevant risk assessment scenarios from the existing hazard database. However, as required by FFDCA section 408(p), acetamiprid is subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).

EPA has developed the EDSP to determine whether certain substances (including pesticide active and other ingredients) may have an effect in humans or wildlife similar to an effect produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator may designate.” The EDSP employs a two

- tiered approach to making the statutorily required determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a
chemical substance to interact with the estr ogen, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go through Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA
will determine which , if any, of the Tier 2 tests are necessary based on the available data. Tier 2 testing is designed to identify any adverse endocrine

- related effects caused by the substance, and
establish a dose

- response relationship between the dose and the E, A, or T ef fect.

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/data call

- ins for the first group of 67 chemicals, which contains 58 pesticide active ingredients and 9 iner t ingredients. Acetamiprid is not among the group of 58 pesticide active ingredients on the initial list to be screened under thePage 16 of 29

EDSP. Accordingly, as part of registration review, EPA will issue future EDSP orders/data call

ins, requiring the submission of EDSP screening assays for acetamiprid. For further information on the status of the EDSP, the policies and procedures, the list of 67 chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our website: http://www.epa.gov/endo/

.

Cumulative Risk Assessments

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 acetamiprid and any other substances and acetamiprid does not appear to pro duce a toxic metabolite produced by other substances. For the purposes of this tolerance action, therefore,
EPA has not assumed that acetamiprid 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 OPP concerning common mechanism determinations and procedures for cumulating effects from substances f ound to have a common mechanism on
EPA’s website at http://www.epa.gov/pesticides/cumulative/

.

Human Studies

Past acetamiprid risk assessments rely in part on data from studies in which adult human subjects were intentionally exposed to a pesticide to determine their dermal and inhalation exposure. These data, which include studies from the Pesticide Handlers Exposure Database Version 1.1 (PHED 1.1); the Outdoor Residential Exposure Task Force (ORET F) database; the Agricultural

Re

- entry Task Force (ARTF) database; and other registrant

- submitted exposure monitoring studies, are subject to ethics review pursuant to 40 CFR 26, have received that review, and are compliant with applicable ethics requireme nts. 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.

Data Requirements

At this time, the Agency has identified only one data gap for information needed to conduct a comprehensive assessment of health risks:

Toxicology : 28 day inhalation Toxicity Study in Rats

R eferences

Bangs, G., D283286, 10/15/2002: Response to Assessment of Handler Exposure Resulting From the Commercial Application of Acetamiprid to Canola and Mustard Seed.

Collantes , M., D264160, 3/11/2002: EPA and PMRA Joint Review of Occupational and Residential Exposure Assessment for Section 3 Registration of Acetamiprid on Cotton, Leafy Vegetables, Cole Crops, Fruiting Vegetables, Citrus Fruits, Pome Fruits, Grapes, and Canola and Mustard Seed Treatment.Page 17 of 29

Figueroa, Z., D295704, 9/29/2004: Occupational and Residential Exposure Assessment for Proposed Section 3 Registration for Use on Tobacco, Stone Fruits, Cucurbits, Tree Nuts, Tuberous and Corm Vegetables, Termiticide
Perimet er Treatment and General Pest Control Uses.

Figueroa, Z., D304214, D310760, 2/17/2005: Occupational and Residential Exposure Assessment for Proposed Section 3 Registration for General Pest Control Uses.

Dow, M., D343132, 9/11/2007: Occupational Human Exposure/Risk Assessment for the Proposed Use of Acetamiprid for Commercial Treatment of Potato Seed Pieces.

Figueroa, Z., D345240 and D310760: 10/24/2007: Occupational/Residential Exposure Assessment for Proposed Use on Stone Fruits, Cucurbit Vegetabl es, Tree Nuts, Berries, Bulb Vegetables, Edible Podded Legumes and
Succulent Shelled Peas and Beans and Insecticide/Termiticide Uses.

Figueroa, Z., D355774, 9/11/2008: Occupational/Residential Exposure Assessment for Proposed Use on Ornamentals and Veget able Transplants (leafy and fruiting vegetables, cole crops, cucurbits, onions and other bulbs.

Figueroa, Z., D353040, 12/1/2008: Occupational/Residential Exposure Assessment for Proposed Use on
Indoor/Outdoor Household Pest Control.

Wang , S

- C., D35709, 1 2/27/2008: Occupational/Residential Exposure Assessment for Amendment of Acetamiprid Use to Include Basal Bark Treatment and Direct Injection on Trees.

Oonnithan, S., D36670, 10/9/2009: Occupational and Residential Exposure Assessment for the New Uses on Clover Grown for Seeds and Tomatoes Grown in Greenhouses and for Increasing the Application Rate on Grapes.

Collantes, M., D383325, 7/22/2011: Occupational/Residential Exposure Assessment for Use to Control Bed Bugs.

Oonnithan, S., D389062 and D389097, 11/16/2011: Occupational and Residential Exposure Assessment for the New Uses in Food/Feed Handling Establishments and on Soybeans.

Oonnithan, S., D 395470, 2/15/2012. Occupational and Residential Exposure Assessment for the Propose d New Uses on Asparagus and Sweet Corn, and for an Increased Application Rate for Turnip Greens.

Rury, K., TXR 52354, 3/15/2012. Summary of Hazard and Science Policy Council (HASPOC) Meeting:
Recommendation on the need for a 28

- day inhalation study.

Holman, E. D394322, 04/19/2012. Acetamiprid: Human Health Risk Assessment for New Uses on Asparagus; Brassica, Leafy Greens, Subgroup 5B, and Turnip Greens; and Sweet Corn; and Updated Crop Group Definitions for Fruiting Vegetables, Citrus, and Pome Fr uit

.

Attachment s Attachment 1. Chemical Identity Table
Attachment 2 . International Residue Limit Status
Attachment 3

. Acetamiprid Products and Use Sites
Attachment 4

. Acetamiprid Endpoint Selection TablesPage 18 of 29

Attachment 1

. Chemical Identity Table

Chemical Identity

Common Name Acetamiprid

CAS Name ( E )

- N 1

- [(6

- chloro

- 3

- pyridyl)methyl]

- N 2

- cyano

- N 1

- methylacetamidine

IUPAC Name (1 E )

- N

- [(6

- chloro

- 3

- pyridinyl)methyl]

- N'

- cyano

- N

- methylethanimidamide

PC Code s 099050

Chemical Abstracts Number s 135410

- 20

- 7

Registration Review Case No. 7617

Chemical Class neonicotinoid

Vapor Pressure 7.5 x 10 - 9 (at 25 C)

Chemical Structure (Acetamiprid)

Chemical Structure of Acetamiprid Metabolite

IM

- 2

- 1

N 1

- [(6

- chloro

- 3

- pyridyl )methyl]

- N 2

- cyano

- acetamidine

Chemical Structure of Acetamiprid Metabolite

IM

- 2

- 1

- amide (also referred to as IM

- 2

- 2)

N 2

- aminocarbonyl

- N 1

- [(6

- chloro

- 3

- pyridyl)methyl]acetamidine N N

H Cl

C H 3

N

O N H 2 N N

H C
l

C H 3

N C N N N

C H 3 C
l

C H 3

N C NPage 19 of 29

Attachment 2 . International Residue Limit (IRL) Status



### Acetamiprid (PC Code 099050)

Summary of US and International Tolerances and Maximum Residue Limits Residue Definition : US Canada Mexico 2 Codex 3,4
Plant: acetamiprid (1 E )

- N

- [(6

- chloro

- 3

- pyridinyl)methyl]

- N'

- cyano

- N

– methylethanimidamide

Livestock: acetamiprid and (1 E )

- N

- [(6

- chloro

- 3

- pyridinyl)methyl]

- N'

- cyano

- N

- ethanimidamide Plant: ( E )

- N

- [(6

- chloro

- 3

- pyridinyl)methyl]

- N'

- cyano

- N

methylethanimidamide

Livestock:( E )

- N

- [(6

- chloro

- 3

- pyridinyl)methyl]

- N'

- cyano

- N

methylethanimidamide, including the metabolite ( E )

- N

- [(6

- chloro

- 3

- pyridinyl)methyl]

- N'

- cyanoethanimidamide Plant: Acetamiprid.
Livestock:
S um of acetamiprid and its desmethyl (IM

- 2

- 1) metabolite, expressed as acetamiprid. The
residue is not fat

soluble.

Commodity Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico 1 Codex 2

Almond, hulls 5.0 Berry, low growing subgroups 13

– 07G 0.60 0.6 lowbush blueberries, lingonberries 2 berries and other small fruits (except grapes and strawberries) 0.5 strawberry Bushberry subgroup 13

– 07B 1.6 0.6 aronia berries, buffalo currants, Chilean guavas, currants, elderberries, European barberries, gooseberries, highbush blueberries highbush cranberries honeysuckle, huckleberries, jostaberries, lingonberries, lowbush blueberries, native currants,
sala l berries, saskatoon berries (juneberries), sea buckthorn 2 berries and other small fruits (except grapes and strawberries)

Caneberry subgroup 13

– 07A 1.6 2 berries and other small fruits (except grapes and strawberries)

Canola, seed 0.010 0.01 rapeseeds (canola) Citrus, dried pulp 1.20 1.2 dried citrus fruit pulp Cotton, gin byproducts 20.0 Cotton, undelinted seed 0.60 0.6 0.7 cotton seed Fruit, citrus, group 10 0.50 0.5 calamondin , citrus citron, citrus hybrids, grapefruits, kumquats, lemons, limes, oranges, pummelos, tangerines,
Satsuma mandarins 0.8 citrus fruitsPage 20 of 29

Summary of US and International Tolerances and Maximum Residue Limits Residue Definition : US Canada Mexico 2 Codex 3,4
Fruit, pome, group 11 1.0 1.0 apples, Asian pears, crabapples, loquats, mayhaws, pears, quinces 0.8 pome fruits

Fruit, small, vine climbing, except fuzzy kiwifruit, subgroup 13

- 07F 0.35 0.6 gooseberries 0.2 grapes 2 berries and other small fruits (except grapes and strawberries) 0.5 grapes Fruit, stone, group 12, except plum, prune 1.20 0.7 apricots, nectarines, peaches, sweet cherries, tart
cherries 0.2 plumcots, plums, prune plums 1.5 cherries
0.7 nectarine 0.7 peach 0.2 plums (including prunes) 0.6 prunes Grain, aspirated fractions 5.0 Mustard, seed 0.010 0.01 Nut, tree, group 14 0.10 0.06 tree nuts Onion, bulb, subgroup 3

– 07A 0.02 0.02 garlic, onion
bulb Onion, green, subgroup 3

– 07B 4.5 5 spring onion

Pea and bean, succulent shelled, subgroup 6B 0.40 0.4 beans, except broad bean and soya
bean 0.3 beans, shelled 0.3 peas, shelled (succulent seeds)

Pistachio 0.10 0.06 tree nuts Plum, prune, dried 0.40 0.4 dried prune plums Plum, prune, fresh 0.20 0.2 plumcots, plums, prune plums 0.2 plums (including prunes) 0.6 prunes Soybean, hulls 0.04 Soybean, seed 0.03 0.3 beans, shelled Tea, dried 1 50.0 Tomato, paste 0.40 0.4 Vegetable, brassica, leafy, group 5 1.20 1.2 bok choy Chinese cabbages, broccoli, broccoli raab, Brussels sprouts, cabbages, cauliflower, Chinese broccoli, C hinese mustard cabbages, collards, kale, kohlrabi, mustard greens, mustard spinach, napa Chinese cabbages, rape greens 0.7 cabbages, head
0.4 flowerhead brassicas (includes broccoli: broccoli,
Chinese and cauliflower)

Vegetable, cucurbit, group
9 0.50 0.2 fruiting vegetables, cucurbits (except sweet corn and mushrooms)Page 21 of 29

Summary of US and International Tolerances and Maximum Residue Limits Residue Definition : US Canada Mexico 2 Codex 3,4
Vegetable, fruiting, group
8 0.20 0.2 bell peppers, eggplants. ground cherries, non

- bell peppers, pepinos, pepper hybrids, tomatillos, tomatoes 0.2 fruiting vegetables other than

cucur bits 2 peppers chili, dried Vegetable, leafy, except brassica, group 4 3.00 3.0 amaranth, arugula, cardoon, celery, celtuce , Chinese celery, corn salad, dandelion leaves, dock, edible leaved chrysanthemum, endives, fresh chervil leaves, fresh Florence fennel leaves and stalks, fresh parsley leaves, garden cress, garden pursiane , garland chrysanthemum, head lettuce,
leaf lettu ce, New Zealand spinach, orach leaves, radicchio, rhubarb, spinach, S wiss chard, upland cress, vine spinach, winter purslane 1.5 celery 3 leafy vegetables (except spinach) 5 spinach

Vegetable, legume, edible podded, subgroup 6A 0.60 0.4 beans, except
broad bean and soyabean 0.3 beans, shelled 0.3 peas, shelled (succulent seeds) Vegetable, tuberous and corm, group 1 0.01 0.01 potatoes

US [40 CFR §180.505(a)(2)] Canada Mexico 1 Codex 2

Livestock: acetamiprid and (1 E )

- N

- [(6

- chloro

- 3

- pyridinyl)methyl]

- N'

- cyano

- N

- ethanimidamide in or on the following
commodities. Livestock/Daily commodities: (1E)

- N

- [(6

- chloro

- 3

- pyridinyl)methyl]

- N'

- cyano

N

methylethanimidamide, including the
metabolite (1 E )

- N

- [(6

- chloro

- 3

- pyridinyl)methyl]

- N'

- cyanoethanimidamide Animal commodities): sum of acetamiprid and its desmethyl (IM

- 2

- 1) metabolite, expressed as acetamiprid. The
residue is not fat

soluble.

Commodity Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico 2 Codex 3
Cattle, fat 0.10 0. 1 fat of cattle 0.02 mammalian fats (except milk fats) Cattle, meat 0.10 0. 1 meat of cattle 0.02 (fat) meat (from
mammals other than marine mammals) Cattle, meat byproducts 0.20 0.3 meat byproducts of cattle 0.05 edible offal (mammalian) Egg 0.010 0.01 0.01 Goat, fat 0.10 0.1 fat of goats 0.02 mammalian fats (except milk fats)Page 22 of 29

Summary of US and International Tolerances and Maximum Residue Limits Residue Definition : US Canada Mexico 2 Codex 3,4

Goat, meat 0.10 0.1 meat of goats 0.02 (fat) meat (from
mammals other than marine mammals) Goat, meat byproducts 0.20 0.3 meat byproducts of goats 0.05 edible offal (mammalian) Hog, fat 0.10 0.1 fat of hogs 0.02 mammalian fats (except milk fats) Hog, meat 0.10 0.1 meat of hogs 0.02 (fat) meat (from
mammals other than marine mammals) Hog, meat byproducts 0.20 0.3 meat byproducts of hogs 0.05 edible offal (mammalian) Horse, fat 0.10 0.1 fat of horses 0.02 mammalian fats (except milk fats) Horse, meat 0.10 0.1 meat of horses 0.02 (fat) meat (from
mammals other than marine mammals) Horse, meat byproducts 0.20 0.3 meat byproducts of horses 0.05 edible offal (mammalian)

Milk 0.10 0.1 0.02 milks Poultry, fat 0.010 0.01 fat of poultry Poultry, liver 0.050 0.05 (*) poultry
edible offal Poultry, meat 0.010 0.01 meat of poultry 0.01 (*) poultry meat Sheep, fat 0.10 0.1 fat of sheep 0.02 mammalian fats (except milk fats) Sheep, meat 0.10 0.1 meat of sheep 0.02 (fat) meat (from
mammals other than marine mammals) Sheep, meat byproducts 0.20 0.3 meat byproducts of sheep 0.05 edible offal (mammalian)
MRLs with no US equivalent

None None Completed: : M. Negussie; 04/30/2012

1 There are no U.S. registrations as of February 10, 2010, for the use of acetamiprid on dried tea.

2 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.

3 * = absent at the limit of quantitation; Po = postharvest treatment, such as treatment of stored grains. PoP = processed postharvest treated commodity, such as processing of treated stored wheat. (fat) = to be measured on the fat portion of the sample.

4 All Codex MRLs are proposed ( have not been finalized by the CCPR and the CAC )

.

3) A tolerance of 0.01 ppm is established for residues of the insecticide acetamiprid, including its metabolites and degradates, in or on all food/feed items (other than those covered by a higher tolerance in paragraph (a)(1) or (a)(2) of this section as a result of the use on growing crops) as a result of the application of acetamiprid in food/feed handling establishments. Compliance with the 0.01 ppm tolerancePage 23 of 29

level is to be determined by measuring only acetamiprid (1 E )

- N

- [(6

- chloro

- 3

- pyridinyl)methyl]

- N'

- cyano

- N

- methylethanimidamide in or on the commodities.

(c) Tolerances with regional registrations. Tolerances with regional registrations are established for
residu es of the insecticide acetamiprid (1 E )

- N

- [(6

- chloro

- 3

- pyridinyl)methyl]

- N'

- cyano

- N

- methylethanimidamide, including its metabolites and degradates, in or on the commodities in the table below as a result of the application of acetamiprid. Complianc e with the tolerance levels specified below is to be determined by measuring only acetamiprid in or on the following commodities.

Commodity Parts per million

Clover, forage 0.10

Clover, hay 0.01Page 24 of 29

Attachment 3

– Acetamiprid Products and Use Sites

FIFRA Sec. 3 Registrations

Table 1 . Use Patterns of Sec. 3 End

- use Product Formulations of Acetamiprid Insecticide

. Registered products & Formul. Types % AI Use Sites and Applicable ORE Reviews Application equipment Comments

8033

- 20
Technical 99.5 NA NA

8033

- 21 Liquid, RTU 0.006 - flowers and ornamental and house plants, leafy vegetables, cole crops, fruiting vegetables, citrus and pome fruits (Collantes, D264160, 3/11/2002)

. Battery operated hand sprayer

8033

- 22, WSP 70 - bedding

- , foliage

- , and potted flowering plants, and plants grown in greenhouses, flowers grown for cutting, ornamental trees, non

- bearing fruit and

nut trees (Collantes, D264160, 3/11/2002)

. Handwand, backpack, handgun

8033

- 23, WP 70 - stone fruits, cucurbits, tree nuts, strawberries and other low growing berries, blueberries and other bush berries, bulb vegetables, edible podded legumes and succulent shelled peas and beans ( Figueroa, D345240 and D310760: 10/24/2007)

.

- grapes & climbing vine small fruits and clover grown for seeds (Oonnithan, D36670, 10/9/2009).

- tuberous and corm vegetables, tobacco, stone fruits, cucurbits, tree nuts ( Figueroa, D295704, 9/29/2004).

- cotton, leafy vegetables, cole crops, fruiting vegetables, citrus, pome fruits, and grapes (Collantes, D264160, 3/11/2002).

- asparagus and turnip greens ( Oonnithan

, D 395470

, 2

/ 15 /20 1 2).

- canola and mustard (Collantes, D264160, 3/11/2002 and Bangs, D283286, 10/15/2002). Air, ground broadcast, airblast, chemigation Seed treatment,
commercial 8

8033

- 24, DF 70 Cotton Air and ground 1

8033

- 25 WSP
8033

- 26 WSP 70 - termite and indoor/outdoor treatment ( Figueroa, D295704, 9/29/2004). Handwand, backpack, handgun

8033

- 28,

- 29,

- 30, and

- 31
Bait 0.15 - indoor/outdoor of homes and other structures ( Figueroa, D304214, D310760, 2/17/2005). By hand

8033

- 32,

- 33,

- 34, and

- 35
Bait 0.35 - indoor/outdoor of homes and other structures, and food/feed handling establishments ( Figueroa, D304214, D310760, 2/17/2005). Handwand, backpack, handgun

8033

- 36 SG 30 - stone fruits, cucurbits, tree nuts, berries, bulb vegetables, edible podded legumes and succulent shelled peas and beans ( Figueroa, D345240 and D310760: 10/24/2007).

- grape & climbing vine small fruits and clover grown for seeds (Oonnithan, D36670, 10/9/2009). Air, ground broadcast, airblast 2Page 25 of 29

Table 1 . Use Patterns of Sec. 3 End

- use Product Formulations of Acetamiprid Insecticide

. Registered products & Formul. Types % AI Use Sites and Applicable ORE Reviews Application equipment Comments

- cotton, leafy vegetables, cole crops, fruiting vegetables, citrus, pome fruits, tuberous and corm vegetables, tobacco.

8033

- 90,

- 91,

- 92, and

- 93
Gel/bait 0.35 - indoor/outdoor of homes and other structures and food handling establishments ( Figueroa, D304214, D310760, 2/17/2005). By hand

8033

- 94, SG 30 - ornamentals and vegetable transplants ( Figueroa, D355774, 9/11/2008).

- basal bark and tree injection ( Wang, D35709,
1 2/27/2008) , and

- tomatoes grown in greenhouse (Oonnithan, D36670, 10/9/2009). Handwand, backpack, handgun, Tree injector

8033

- 95, EC 40

- potato seed pieces Dow ( D343132, 9/11/2007). Seed piece

treatment On

- farm/
commercial

8033

- 96, WSP 22.73 - termite, outdoor perimeter, indoor C&C ( Figueroa, D345240

, D310760: 10/24/2007, and Figueroa, D353040, 12/1/2008). Handwand, backpack, handgun

8033

- 97,

- 98,

- 99,

- 100, and

- 105 Gel/ baits 0.075 - indoor and/or outdoor of homes, apartments, food handling establishments. By hand 3

8033

- 101, EC 8.5

- cotton Air and ground
broadcast 1

8033

- 106, EC 8.5 - ornamentals and vegetable transplants ( Figueroa,

- basal bark and tree injection

- tomatoes grown in greenhouse Handwand, backpack, handgun, tree injector 4

8033

- 107 Liquid, Ready to Use (RTU) 0.5 - indoor/outdoor residential ornamentals (annuals, shrubs and trees), vegetables, and fruits. Hand sprayer,
hose

- end, tank

sprayer 5

8033

- 108 Liquid, RTU 0.26 - indoor and outdoor residential ornamentals (annuals, shrubs and trees). Hand sprayer,
hose

- end, tank

sprayer 5

8033

- 109, EC 5 - termite, indoor and outdoor pests in residential, public and commercial structures. Handwand, backpack, handgun 6

8033

- 114, and

- 115, Fly Bait
stations 4.4 - indoor/outdoor; industrial and commercial trash

areas. By hand 7

Abbre viations used: AI = active ingredient, C&C = crack and crevice, DF = dry flowable, EC = emulsifiable concentrate, NA = not applicable, RTU = ready to use, SG = soluble granule, WP = wettable powder, WSP = water soluble package. 1. SG and EC formulations were not assessed; but, the dermal and inhalation unit exposures being lower than that of WP for the same use patterns, the WP MOEs is expected to be protective. 2. Exposure from SG on some sites was not assessed. WP MOEs would be protective if use of WP is registered. 3. The 0.075% bait gel was not assessed; a 0.35% gel was assessed and would be protective ( Figueroa, D304214, D310760, 2/17/2005).
4. The 8.5% EC was not assessed; a 30% SG was assessed and would be protective ( Figueroa, D355774, 9/11/2008, Wang

, D35709, 1 2/27/2008, and Oonnithan, D36670, 10/9/2009).Page 26 of 29

5. Not assessed , but the application rate is expected to be lower than WP and SG formulations applied on ornamentals in residential settings. 6. The EC formulation was not assessed, but a 70% WSP was assessed for the same uses and rates and risks are not
of concern ( Figueroa, D295704, 9/29/2004).
7. Not assessed

, but exposures are expected to be insignificant due to incorporation of acetamiprid in the glue. However, in case of bleeding of acetamiprid/glue mix (due to higher temperature when used indoors and outdoors )

, applying by hand would result in dermal exposure. 8. Due to inhalation LOC of 1000, crops with aerial applications ≥0.1 lb ai/ A may require P F 5 respirator for
mixer/loader , in order to be protective.

FIFRA Sec. 24(c) Registrations

There are a number of Special Local Need ( SLN ) also known as FIFRA Sec. (24c) registrations for acetamiprid insecticide (Table 2). These SLN sites may not have been reviewed for occupational exposures; however, ORE reviews conducted for the same or similar sites would support the SLN uses. These comparable ORE reviews are discussed below.

Table 2

. Use Patterns of SLN Registrations of Acetamiprid Insecticide

. SLN No. and Parent Reg. No. % AI of
Parent Use Site Single Appl. Rate
and Method Comments 1

ID070011 (8033

- 23) 70 WP

Alfalfa seed crop 0.075 lb ai/A Foliar ground and aerial Aerial application may require

re

- evaluation ID090014 (8033

- 36) 30 SG NV070004 (8033

- 23) 70 WP OR070017 (8033

- 23) 70 WP UT090001(8033

- 23) 70 WP WA070006 (8033

- 23) 70 WP WY080010 (8033

- 23) 70 WP OK100001 (8033

- 96) 22.73 WSP Post

- construction, sub

concrete treatment using piping, injector,
reticulation etc. for
termite control 0.00184 lb ai/gal per linear ft. A higher rate (0.0043 lb ai/gal) ha s been assessed OK100003 (8033

- 96

- 279) 22.73 WSP

OK110002 (8033

- 109) 5 EC

OR090005 (8033

- 23) 70 WP Hybrid poplar grown
for wood 1.2 mg ai/A plus pheromone Spot, trap attached to trees to attract & kill carpenter worm Not assessed
but not of
concern due to very low appl. rate WA060009 (8033

- 94) 30 SG

Apples, pears, etc. 0.15 lb ai/A Foliar ground Spraying in
residential areas require s

re

- evaluation WA060011 (8033

- 22) 70 WSP

WA110010 (8033

- 106) 8.5 EC

1. Rationale used to support ORE assessment for the SLN site is described in the text.

A lfalfa seed crop : Several Western States have registered WP and SG formulations of acetamiprid for controlling lygus bug infestations on alfalfa. No occupational handler exposure was evaluated for this use. However, an ORE assessment conducted for the same products (70%

W P and 30% SG) on clover grown for seed applied at a maximum single application rate of
0. 075 lb ai/A would be protective of handler and postapplication exposures (S. Oonnithan, D366701, 10/9/2009). A re

- evaluation of handler exposure may be required when the WP formulation of acetamiprid is applied on 1,200 acres/day using aerial equipment because treating 350 A of clover per day resulted in a n MOE of 380 with a LOC of 100 at baseline PPE plusPage 27 of 29

gloves (the re

- evaluation would be needed for inhalation exposu re only, based on the LOC of 1000 for that route of exposure)

.

Termite t reatment : The State of Oklahoma has two SLNs for treating new and post

- construction
sub

- concrete slabs for termite control. The application methods used are piping, injector,
reticu lation (tubes placed under slabs for future treatments), or similar sub

- concrete slab delivery systems. No occupational handler exposure w as evaluated for this use. However, a comparable
ORE assessment (Z. Figueroa, D345240, 10/24/2007)

, where a 22.73% a cetamiprid WSP formulation applied with a hand gun and low

- pressure handwand at 0.0043 lb ai/gal at 1,000 gal/day (as compared with SLN’s 0.00184 lb ai/gal / linear ft. ) is expected to be protective of

p iping and reticulation systems allowed for under the OK SLNs

.

Apple maggot control : The State of Oregon has registered three SLNs as a quarantine and pest free program to control apple maggots on apples, crabapples, pears, ornamental plants and trees
and non

- bearing fruit and nut trees growing in non

- agricul tural and residential areas. No occupational (handler) and likely residential postapplication exposure (to adults and children) were evaluated for this use. However, a comparable ORE assessment (M. Collantes, D264160, 3/11/2002) consisting of a erial appl ication using the 70% WP ( Reg. No. 8033

- 23 ) on pome fruits applied at 0.15 lb ai/A (same application rate as in SLNs) would be protective of ground applications of all the three SLNs used on apple and other trees.Page 28 of 29

Attachment 4

. Acetamiprid Endpoint Selection Table

Summary of Toxicological Doses and Endpoints of Acetamiprid for Use in Dietary and Non

- Occupational Human
Health Risk Assessment Exposure Scenario Dose Used in

Risk
Assessment Uncertainty

Factors/FQPA Safety Factors PAD ; Level of

Concern for
Risk
Assessment Study and Toxicological Effect

Acute Dietary (All populations) NOAEL = 10

mg/kg/day UF A = 10x

UF H = 10x FQPA SF = 1x aPAD = 0.10

mg/kg/day Co

- critical studies

Developmental Neurotoxicity in rat LOAEL = 45 mg/kg/day based on decreased early pup survival on PND 0

- 1, and decreased startle response on PND 20/60 in males. Acute Neurotoxicity Study in rat LOAEL = 30 mg/kg/day based on decreased locomotor activity Chronic Dietary all populations NOAEL = 7.1

mg/kg/day UF A = 10x

UF H = 10x FQPA SF = 1x cPAD = 0.071

mg/kg/day Chronic Toxicity/ Oncogenicity Study

in rats LOAEL = 17.5 mg/kg/day based on decreased body weight and body weight gains in females and hepatocellular
vacuolation in males.

Short

- and
Intermediate

- Term
Incidental Oral (1

- 30 days and 1

- 6 mo.) NOAEL = 10

mg/kg/day UF A = 10x

UF H = 10x FQPA SF = 1x LOC for MOE

= 100 Developmental Neurotoxicity in rat

LOAEL = 45 mg/kg/day based on decreased body weight and body weight gains in offspring, decreased early pup
survival on PND 0

- 1, and decreased startle response on PND 20/ 60 in males.

Short

- and
Intermediate

- term Dermal (1

- 30 days, 1

– 6 mo.) NOAEL = 10

mg/kg/day

DAF = 10% UF A = 10x

UF H = 10x FQPA SF = 1x LOC for MOE

= 100 Developmental Neurotoxicity in rat

LOAEL = 45 mg/kg/day based on decreased body weight and body weight gains in offspring, decreased early pup
survival on PND 0

- 1, and decreased startle response on PND 20/60 in males.

Short

- and
Intermediate

- term Inhalation (1

- 30 days, 1

– 6 mo.) NOAEL = 10

mg/kg/day UF A = 10x

UF H = 10x

UF DB = 10X LOC for MOE

= 100 0 Developmental Neurotoxicity in rat

LOAEL = 45 mg/kg/day based on decreased body weight and body weight gains in offspring, decreased early pup
survival on PND 0

- 1, and decreased startle response on PND 20/60 in males. Cancer (oral, dermal, inhalation)

- not likely to be carcinogenic to humans (2005 revised Agency cancer guidelines).
DAF = dermal absorption factor. 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 expos ures. NOAEL =
no ob served adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = potential variation in sensitivity among members of the human population (intraspecies). FQPA SF = FQPA Safety

Factor. UF DB = data base uncertainty factor. PAD = population adjusted dose (a = acute, c = chronic) = reference dose /all uncertainty factors

. MOE = margin of exposure. LOC = level of concern. N/A = not applicable.Page 29 of 29

Summary of Toxicological Doses and Endpoints of Acetamiprid for Use in Occupational Human Health Risk
Assessment Exposure Scenario Dose Used in

Risk
Assessment Uncertainty

Factors Level of

Concern for
Risk
Assessment Study and Toxicological Effect

Short

- , Intermediate

- term Dermal (1

- 30 days, 1

- 6 mo.) NOAEL=

10 mg/kg/day

DAF = 10% UF A = 10x

UF H = 10x LOC for MOE

= 100 Developmental Neurotoxicity in rat

LOAEL = 45 mg/kg/day based on decreased body weight and body weight gains in offspring, decreased early pup
survival on PND 0

- 1, and decreased startle response on PND 20/60 in males.

Long

- term Dermal (> 6 mo.) NOAEL = 7.1

mg/kg/day

DAF = 10% UF A = 10x

UF H = 10x FQPA SF = 1x LOC for MOE

= 100 Chronic Toxicity/Oncogenicity Study in

rats LOAEL = 17.5 mg/kg/day based on decreased body weight and body weight gains in females and hepatocellular
vacuolation in males.

Short

- and
Intermediate

- term Inhalation (1

- 30 days, 1

- 6 mo.) NOAEL=

10 mg/kg/day UF A = 10x

UF H = 10x LOC for MOE

= 100 Developmental Neurotoxicity in rat

LOAEL = 45 mg/kg/day based on decreased body weight and body weight gains in offspring, decreased early pup
survival on PND 0

- 1, and decreased startle response on PND 20/60 in males.

Long

- term Inhalation (1

- 30 days, 1

– 6 mo.) NOAEL = 7.1

mg/kg/day UF A = 10x

UF H = 10x
UF DB = 10X LOC for MOE

= 100 0 Chronic Toxicity/Oncogenicity Study in

rats LOAEL = 17.5 mg/kg/day based on decreased body weight and body weight gains in females and hepatocellular
vacuolation in males. Cancer (oral, dermal, inhalation)

- not likely to be carcinogenic to humans (2005 revised Agency cancer guidelines. 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 ob served adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = potential variation in sensitivity among members of the human population (intraspecies). UF DB = data base uncertainty factor. DAF = dermal absorption factor. MOE = margin of exposure. LOC = level of concern. N/A = not applicable.