UNITED STATES E NV IRONMENTAL PROTECTION AGENCY WASHINGTON, D

. C

. 204 60

OFFICE OF CHEMICAL SAFETY AND

POLLUTION PREV ENTION

MEMORANDUM

Date: 5 /9/ 13

SUBJECT: Fenhexamid. Human Healt h Assessment Scoping Document in S upport of

Re gistrat i on Review.

PC Code: 090209

Dec i sion No .: 

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Petition No.: N/A DP Bar code: D407943 Registration No.: N/A Regulatory Action: Registration Review Scoping Document

Ri sk Assessment Type : N/ A

TXRNo.: N/A Case No.: 7027 -1

CAS No.: 126833-17-8

40 CFR: 180.553 MRID No.: N/A

FROM:

THRU:

TO: Mo n ica H awkins

, Environrnentalj-l ealt h Scientist/Risk Assessor

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. Yvonne Barnes, Chemist**~~..,...__. ~etL~** 

### N~ncy McCarro! l

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### BIOl**ogtst~~Jh 7~** **7** Ri sk Assessment Branch VI

- .**-;]" '**  Health Effects Division (7509 P ) 

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Felecia Fort, Branch Chief

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Health Effects Divis i on (7509P )

Joel Wolf, Chemical R eview Manager

Ri sk Management and Implementation Bran ch II

Product Re -Eva luation Division (7508P)

Attached i s HED's human health r isk assessment scoping docume nt for fenhexamid to support Registration Revi ew.

Executive Summary

Page 1 of22Fenhexamid Registration Review Human Health Scoping Document

Th e most recent human health r i sk asse ss m ent for fenhexam i d, whic h is a fungicide, was completed in 2007 for u se on asparagus (B. Hanson, D347171

, 12/05/2007). HED has

evaluated the status of all previous risk assessments for fenhexarnid to determine whether

sufficient data are available and whether any updates are needed to support Registration R eview.

The previous risk assessments were evaluated wit h respect to fenhexamid's toxicity, exposure,

usa ge databases, and the most updated Agency science policy and risk assessment me thod o l og i es

to determin e the scope of work necessary to support Re g i strat i on Rev i ew.

Fenh examid is a water dispersible granule that is applied on a variety of agricultural and

ornamental crops in the field

, greenhouses

, and in post-harvest production. HE D 's Metabolism

Assessment Review Committee (MARC) concluded that only the parent fenhexamid needs to be

i ncluded in th e tolerance expressi on and used fo r dietary and drinking water risk assessments. Only parent fenhe xamid is of regula t ory concern

.

The toxicology database for fenhexamid is incomplete but sufficient for registration review. In
accordance with the revised 2007 toxicology data requi r ements, the neurotoxicity battery and immunotoxicity studies are required. Additionally, a sub chronic inhalation toxicity study is requir ed if there i s likelihood of re peated inhalation exposure to pesticide chemica l. HED's

Hazard Sc i ence P olicy Counc il (HASPOC) eva l uated all of the availab l e h azar d an d exposure information for fenhexamid and concluded that the sub chronic inhalation is not required based

on: the low acute inhalation toxicity (Toxicity Category IV); lack of systemic toxicity when exposed at 1 .092 mg/L for 5-days and the the composition of the formulated product (waterdispersible granules containing 50% a.i.); the low application rate (maximum of 0.5-0.75 lb ai/Napplication) and application method (ground s p ray, ground boom and airb l ast). The Council

also concluded that a s ub chro nic inhalation study is not required since there was no evidence of

neurot oxicity at th e Limit Dose in an ac u te neurotoxicity study, there i s no eviden ce of neurotoxicity in the subchronic and chronic oral toxicity studies, and the Point of D eparture ( P O D ) use for risk assessment is based most sensitive endpoint (hematopoietic toxicity) observed

in the most sensitive species (dog) and therefore, a sub chronic will not be useful i n the Agency's evalua ti on of risk. OPP has published th e findings of an independent retrospective analy s i s of 170 immunotoxicity s tudi es subm i tted t o th e Agency. Th e retrospective analysis

s h owed that the submitted immunotoxicity st ud ies h ave n ot yet resulted in PODs that are l ower than the PODs selected from other available g u i deline experimen ta l t oxico l ogy studies. As a result, the currently available immunotoxicity studies h ave not impacted the Agency's risk

assessments. HED is in the process of developing guidance on data waiver considerations. In the

interim

, HED recommends that immunotoxicity studies continue to be required for registration
and r eg i stration review chem i cals.

The residue c h e mistr y database for fenhexamid i s comp l ete. However, the chemist r y database

indicates that the registrant has, as a condition of registration, sub mi tted three studies: (MRID

45720 1 01) two additional field trials required to support an individual tolerance on prunes; (MRID 45720102) a processing study required for dried prune matrices; and (MRI D 45720103)

a meth od validation study requi r ed to support dried prune residue data co ll ection. These

docum e nt s have no t yet been reviewed. The mos t recent unrefined dietary r i s k a ssessment
includ ed an updated drinking water assessment for fenhexamid. An acute reference dose (RID)

has not been established for fenhexarnid aRd it is classified as a "not li kely " human carcinogen.

Neither an acute nor a cancer dietary risk assessment is required. For chronic

, the chronic dietary exposure is below the level of concern.

Page 2 of22

### Fenhexamid Registration Review Human Health Scoping Document

Page 3 of 22 There are currently no registered residential uses for fenhexamid; therefore, no short

- and

intermediate

- term aggregate risk assessments are required.

The occupational exposure database is adequate to support the registration review process for

fenhexamid

. U pdated occupational handler exposure assessments may be require d under Registration Review based upon revisions to the Agency’s scenario

- specific handler exposure data. New exposure monitoring data may be incorporated, as necessary, during Registration Review. Updated occupational post

- application exposure assessmen ts may be required under Registration Review based upon revisions to the Agency’s post

- application exposure data and to incorporate chemical

- specific data, as necessary . In addition, revised occupational handler and

post

- application assessments may be nee ded if toxicological endpoints change or other new data are received by the Agency that impact exposure estimates.

Introduction

Fenhexamid is currently registered for field application on almonds, asparagus, bushberries, caneberries, ginseng (except Cali fornia), grapes, pear and oriental pear, pistachios, stone fruit, and strawberries. The chemical is currently registered for transplant production and greenhouse production on the following crops; cilantro (except California), cucumber, fruiting vegetables

, tomatoes, leafy greens (except spinach), and nursery grown ornamentals. Fenhexamid also has

post

- harvest application registered uses on the following crops: cherries, kiwi, pear and oriental pear, pomegranate, and stone fruit.

Information on the chemi cal identify of fenhexamid is included in Attachment 1.

Hazard Identification/Toxicology

The Toxicology Profile Tables are presented in Attachment 2, Table A 2.2 . In general, the toxicology studies conducted on fenhexamid demonstrate that it has few or no biologically significant toxic effects at relatively low doses in many animal studies and only mild or no toxic effects at high doses, which often approach or exceed the limit dose. In subchronic and chronic oral studies, the most toxicologically signi ficant effects were anemia i n dogs, decreased body weights, increased food consumption and mild liver and/or kidney effects in rats and mice. Fenhexamid is not acutely toxic, neurotoxic, carcinogenic or mutagenic and is not a developmental or reproductive toxicant. There was no evidence of increased susceptibility following in utero exposure to rats or rabbits. There was evidence for increase qualitative susceptibility following pre/post natal exposure in the two generation reproduction study. Offspring t oxicity manifested as sever e decreases in the body wei ght of pup in both the F1 and

F2 generations at the same dose that caused parental toxicity characteristic of hepatotoxicity. HED’s Hazard Identification Assessment Review Committee (HIARC) determine d that there is low concern for pre

- and/or postnatal toxicity resulting from exposure to fenhexamid (Tarplee, 2003). The rationale for this decision was based on the evidence showing no increased susceptibility in the offspring in either the rat or rabbi t developmental toxicity studies and that a

clear No Observed Adverse Effect Level ( NOAEL ) and a well

- characterized dose response for offspring effects was observed in the presence of maternal toxicity. Accordingly, the doses

### Fenhexamid Registration Review Human Health Scoping Document

Page 4 of 22 selected for the risk assessm ent would be protective of the susceptibility of the young. HIARC also determined that no FQPA safety factor is needed (i.e. 1X) since there are no residual uncertainties for pre and/or postnatal toxicity. In addition the HIARC concluded that there is no t a concern for developmental neurotoxicity resulting from exposure to fenhexamid. Minimal or no toxic effects were observed in studies in which fenhexamid was administered by the dermal or inhalation routes of exposure.

In a battery of five mutagenicity studies (with and without metabolic activation, as appropriate for the specific study), technical grade fenhexamid was negative for genotoxicity.

Based on the lack of evidence of carcinogenicity in male and female rats as well as in male and female mice and on the lack of genotoxicity in an acceptable battery of mutagenicity studies,
fenhexamid is classified as a “ not likely ” human carcinogen according to the EPA Proposed Guidelines for Carcinogen Risk Assessment (April 10, 1996).

The fenhexamid endpoints, points of departure (POD), and uncertainty/safety factors (UF/SFs) are summarized in Attachment 3, Tables A 3.1 and A 3.2. HED concluded that an aRfD was not selected for the acute dietary risk assessment because no a ppropriate toxicological endpoint attributable to a single exposure was identified in the available toxicology studies, which included an acute neurotoxicity study in rats and developmental studies in rats and rabbits (Hansen, 2007). Since that time, no n ew studies have been submitted.

The chronic Reference Dose ( cRfD) of 0.17 mg/kg/day was based on toxicological findings in

the 1

- year chronic dog feeding study of decreased RBCs, decreased hemoglobin and hematocrit,

and increased Heinz bodies in males an d females, as well as increased adrenal weights and intracytoplasmic vacuoles in females at the Lowest Observed Adverse Effect Level ( LOAEL) of 124 mg/kg/day (See Attachment 3, Table A 3.1). An uncertainty factor of 100 (10X for interspecies and 10X for in traspecies v ariations) was applied to the NOAEL of 17 mg/kg/day.

Since there are no residential exposures, endpoints were not selected for incidental oral (short

and intermediate

- term), dermal (short

- , intermediate

- or long

- term) or inhalation (short

- , intermediate

- or long

- term) scenarios.

Occupational exposure via the dermal route is expected. Accordingly, the 21

- day dermal toxicity study was selected for the short

- and intermediate

- term dermal risk assessments, based on the NOAEL of 1000 mg/kg/day (HDT, Limit dose). HIARC (TXR No. 0051704, 3/26/2003) justified this selection because the results of this study were consistent with those of the oral developmental toxicity study in rabbits in which maternal effects (decreased body weight gain
and decre ased food consumption) were observed, particularly during the first week of dosing at the LOAEL of 300 mg/kg/day (See Attachment 3, Table A 3.2). The NOAEL for maternal toxicity in this study was 100 mg/kg/day. Using the 20% dermal absorption factor (See Attachment 2, Table A 2.2) derived from the submitted dermal absorption study, the oral LOAEL (300 mg/kg/day) is equivalent to a dermal LOAEL of 1500 mg/kg/day. Therefore, since

treatment

- related effects were observed at an equivalent dermal dose, the de rmal NOAEL of 1000 mg/kg/day would be appropriate. Long

- term dermal exposure is not expected.

Based on the low acute inhalation toxicity (Toxicity Category IV) (See Attachment 2, Table A 2.1) , the low 5

- day subchronic toxicity (no systemic toxicity at 1.0 92 mg/L), the composition of the formulated product (water

- dispersible granules containing 50% a.i.), the application rate

### Fenhexamid Registration Review Human Health Scoping Document

Page 5 of 22 (maximum of 0.5

- 0.75 lb ai/A/application ) , and acceptable MOE s, HASPOC determined that a

s ubchronic inhalation study is not required.

HASPOC, nevertheless, chose to exam ine the short

- and intermediate

- term inhalation exposure for possible risks to workers because of the various application scenarios including high pressure hand held equipment in enclosed areas, such as greenho uses

. Accordingly, the two

- generation reproduction study in rats (MRID 44346803) with a NOAE L of 38 mg/kg/day and a LOAEL of 406 mg/kg/day was chosen for this assessment. Inhalation and oral absorption were assumed to be equivalent. The level of concern (LOC) for the occupational exposures was a margin of exposure (MOE) >1000, which is considered the benchmark for granting an inhalation waiver. Based on this analysis, inhalation exposure scenarios were found to have MOE s > 1000 and are
not of concern

.

Lo ng

- term inhalation exposure is not expected.

Conclusions

The toxicology database for fenhexamid is incomplete but sufficient for registration review. Although the 21/28

- day subchronic inhalation study, the 90

- day neurotoxicity study, and the immunotoxicity study are required in accordance with new data requirements for conventional pesticide registration (40 CFR Part 158), HASPOC waived both the 21/28

- d ay subchronic
inhalation and the 90

- day neurotoxicity studies; the immunotoxicity study remains a data requirement.

Endocrine Disruption

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and chronic toxicity, including assessments of carcinogenicity, neurotoxici ty, developmental, reproductive, and general or systemic toxicity. These studies include endpoints which may be susceptible to endocrine influence, including effects on endocrine target organ histopathology, organ weights, estrus cyclicity, sexual maturati on, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess growth, developmental and reproductive effects in different taxonomic groups. As part of its reregistration decision , EPA reviewed these data and selected the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. However, as required by FFDCA section 408(p), fenhexamid is subject to the

end ocrine 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 estrogen, 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 syste ms will proceed to the next stage of the EDSP where EPA

### Fenhexamid Registration Review Human Health Scoping Document

Page 6 of 22 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

e stablish a dose

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

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 grou p of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. Fenhexamid is not among the group of 58 pesticide active ingredients on the initial list to be screened under the EDSP. Accordingly, as part of registration review , EPA will issue future EDSP orders/data call

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

.

Dietary Exposure

The residue chemistry database for fenhexamid is complete and sufficient for registration review. Adequate na ture of the residue studies is available for plants and livestock . The only residue of concern, used to establish tolerances and used for risk assessment purposes in plants and

livestock , is the parent fenhexamid. The Agency previously concluded that a 30

- day plant

- back interval should appear on the label and apply to all crops without a registered use. The Elevate 50 WDG registered label specifies a 30

- day plant

- back restriction for no n

- label crops. The label plant

- back interval is adequate; no additional data are required relative to rotational crops.

An adequate analytical method for enforcing tolerances in plant and livestock matrices is available. Data validation studies (MRID 45720103) for data collection of prune matrices is also available and requires scheduling for e valuation during the registration review process. Field trial data generated using acceptable data collection methods for all other commodities and supported by a dequate storage stability data are available for each registered crop. The required dried prune processing study (MRID 45720102) is available and requires scheduling for evaluation during the registration review process. Additionally, two field trial s tudies (MRID 45720101) in support of an individual tolerance on dried plums is available and will require scheduling for analysis during the registration review process. Adequate livestock feeding studies are available for fenhexamid. The Agency previously concluded that there is no reasonable expectation of finite residues [40 CFR §180.6(a)(3)] in milk or ruminant tissues as a result of the currently proposed uses.

A chronic dietary assessment was conducted assuming tolerance

- level residues for all

commod ities with existing and proposed tolerances and 100% crop treated (CT). For the U.S. population the exposure for food and water utilized 10% of the cPAD. The chronic dietary risk estimate for the highest reported exposed population subgroup, children 1

- 2 years old, is 27% of

the cPAD.

The Environmental Fate and Effects Division (EFED) conducted a drinking water assessment (DP#: 338651, C. Sutton, 07/26/2007), which modeled separately the estimated drinking water concentrations (EDWCs) for fenhexamid re sidues of concern . However, the residue of concern

### Fenhexamid Registration Review Human Health Scoping Document

Page 7 of 22 was identified as only the parent (Herndon 1999), EFED may revisit this determination in Registration Review

. If no new relevant data regarding the environmental fate, toxicity, or uses of parent fenhexa mid is submitted, the EDWCs from the most current drinking water assessment may be used in the registration review risk assessment. The Agency previously conducted an

unrefined chronic risk assessment for fenhexamid. The dietary assessment included the us e of field trial data and empirical processing factors, as well as modeled drinking water values.

Conclusions

The residue chemistry database is complete and sufficient for registration review. However,

the re are studies previously submitted, as a condition of registration

, which require scheduling

for evaluation during the registration review process: two field trial studies on plums (MRID 45720101), dried prune processing study (MRID 45720102) and d ata validation stud y (MRID 45720103). Pend ing the results of these three studies, the database currently indicates that all other data requirements for residue chemistry are adequate.

Also, a new dietary assessment may be needed if one or more of the following occur: new data

are identified whi ch impact dietary exposure estimates, including those from drinking water; new toxicological points of departure are identified, including revisions to the FQPA SF; Office of Pesticide Program dietary exposure policies and procedures are revised. HED has updated its dietary model to incorporate more recent consumption data from the National Health and Nutrition Examination Survey (NHANES). The newer version of the model will be used during registration review if a new dietary assessment is needed.

Residen tial Exposure and Risk

There are no residential uses for fenhexamid; therefore, a residential exposure assessment will not be required.

Residential bystander inhalation exposures resulting from off

- site transport (e.g., spray drift or volatilization) may occur as a result of applications of fenhexamid . The Agency is in the process of evaluating these types of exposures and will examine the need for spray drift and

volatil ization assessments for fenhexamid during registration review.

Aggregate Risk Assessment

There are currently no registered residential uses, nor are any proposed for fenhexamid. Therefore, at this time, dietary (food + water) exposure is the only compon ent of an aggregate exposure analysis and risk assessment.

Conclusions for Aggregate Exposure and Risk Assessment

Updated aggregate exposure and risk assessments may be required under registration review based on the need for directly incorporating dri nking water estimates into the dietary assessment. These revised aggregate exposure and risk assessments may also reflect any toxicological endpoint changes or other new data are received by the Agency that may impact exposure

estimates.

### Fenhexamid Registration Review Human Health Scoping Document

Page 8 of 22 Occupational Exposure

As noted above, fenhexamid is registered for field application to almonds, asparagus, bushberries, caneberries, ginseng (except California), grapes, pear and oriental pear, pistachios, stone fruit, and strawberries. The chemical is also current ly registered for transplant production and greenhouse production on the following crops; cilantro (except California), cucumber, fruiting vegetables, tomatoes, leafy greens (except spinach), and nursery grown ornamentals. Lastly, fenhexamid uses include p ost

- harvest application on the following crops; cherries, kiwi, pear and oriental pear, pomegranate, and stone fruit. The Agency has determined that there is a potential for occupational handler and post

- application exposures resulting from the registered

uses of fenhexamid.

Occupational Handlers

In 2006, HED evaluated a number of occupational handler scenarios that represented the major fenhexamid occupational handler scenarios for field

- base d application equipment based on the water dispersible granular formulation type. The assess m ent indicated that occupational handler scenarios resulted in no risks of concern for the highest expected dermal exposure scenarios (e.g., mixer/loaders using ope n pour loading of granules and applicators using open

- cab, ground

boom spray equipment). Application sites including greenhouses and post

- harvest packing plants were last reviewed in 200 6. The assessment also indicated that there were no risks of

concern for the highest expected dermal exposure scenarios associated with transplant, greenhouses, and packing plants, (e.g., mixer/loaders using open pour loading of granules, applicators using high pressure hand sprayers in enclosed situations such as a greenh ouse, and ground boom spray equipment). Groundboom equipment is not an expected application method, due to the estimated size of transplant beds in greenhouses

, but was included in the assessment due to the lack of specific bed data. The post

- harvest frui t treatment is assumed to be an automated process in which the fruit passes along a “line” and is either dipped or sprayed in an automatic hooded situation. Therefore, only occupational loaders were assessed for the post

harvest packing plant application sites.

Occupational Post

- application

Previous assessments were conducted for occupational post

- application scenarios associated with

fenhexamid uses
, including post

- harvest applications in packing plants . D islodgeable foliar residue (D FR ) data are available for fenhexamid, and were used in all of the previous

assessments

, except for post

- harvest treatment

, which used default assumptions . In general,

there were no risk estimate s of concern for any of the post

- application activi ti es assesse d (MOEs

≥ 100).

Technical fenhexamid is currently classified as toxicity category IV for acute dermal toxicity, primary eye, and skin irritation. The restricted

- entry interval was set to 12

- hours for use of fenhexamid on asparagus and other field grown crops.

Based on the Agency's current practices, a quantitative post

- application inhalation exposure

assessment has n ot been performed for fenhexamid to date. However, there are multiple

### Fenhexamid Registration Review Human Health Scoping Document

Page 9 of 22 potential sources of inhalation exposure to individuals performing post

- application 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 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 Agricultural Reentry Task Force 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 ex posure assessment for fenhexamid

.

Conclusions for Occu

pational Exposure and Risks

The occupational exposure database is adequate to support the registration review process for

fenhexamid

. Updated occupational handler exposure assessments may be required under Registration Review based upon revisions to the Agency’s scenario

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

- exposure

- table.pdf ). HED will incorporate new exposure monitoring data , as necessary, during Registration Review. Updated occupational post

- application exposure assessments may also be required under Registration Review based upon revisions to the Agency’s post

- application exposure data. HED will incorporate all available chemical

- specific data, as appropriate, into the occupational exposure assessment for Registration Review. Additionally, revised occupational handler and post

application assessments may also be needed if toxicological endpoints change or other new data

a re received by the Agency that impact exposure estimates.

Human Studies

The previous fenhexamid risk assessments relied in part on data from studies in which adult human subjects were intentionally exposed to a pesticide or other chemical. Studies such as the Pesticide Handlers Exposure Database, Outdoor Residential Exposure Task Force, and Agricultural Handler Exposure Task Force have been reviewed by the Agency and found on the basis of available evidence to have been neither fundamentally unethical n or significantly deficient relative to standards of ethical research conduct prevailing when they were conducted. There is no barrier in EPA's "Protection of Human Subjects" Regulation to reliance on these

studies.

Public Health and Pesticide Epidemiology Data

The Agency has reviewed the available incident data for fenhexamid ( D407943 , S. Recore,

2/21 /13) and concludes that based on the low frequency and severity of incident cases reported for fenhexamid, there doe s 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.

### Fenhexamid Registration Review Human Health Scoping Document

Page 10 of 22 Tolerance Assessm ent and International Harmonization

Tolerances for fenhexamid are established under 40 CFR §180.553, only the parent is of regulatory concern.

According to HED’s Interim Guidance on Tolerance Expressions (05/27/2009, S. Knizner), the tolerance expression for fenhexamid on plant and animal commodities should be revised to state:

Tolerances are established for residues of fenhexamid, including its metabolites and degradate, in or on the commodities as listed in 40 CFR §180.553 . Compliance with the

toleran ce levels specified below is to be determined by measuring only fenhexamid (N

2,3

- dichloro

- 4

- hydroxyphenyl)

- 1

- methyl cyclohexanecarboxamide).

At this time, there are no pending requests to establish a new fenhexamid tolerance.

The International Residue Limit Status Sheets are appended to the end of this document as Attachment 4, Table A 4.1 ( i.e. Harmonized MRLs). There are US

, Codex and Canad a maximum residue limits (MRLs) established for plant and/or animal commodities but there are

no Mexic o MRLs. The U.S. plant residue definition is harmonized with Canada. Also included

in Attachment 4, is Table A 4.2 that lists the commodities for which the re are tolerance differences among the US, Canadian and Codex MRLs.

Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, were considered in the human health risk assessment, in accordance with U.S. Executive Or der 12898, "Federal Actions to Address Environmental Justice in Minority Populations and Low

- Income Populations," http://www.eh.doe.gov/nepa/tools/guidance/Volume1/2

- 6

- EO_12898envjustice.pdf ). The Office of Pesticide Programs (OPP) typically considers the highest potential exposures from the legal use of a pesticide when conducting human health risk assessments, including, but not limited to, people who obtain drinki ng water from sources near agricultural areas, the variability of diets within the U.S., and people who may be exposed when harvesting crops. Should these highest exposures indicate potential risks of concern, OPP further refines the risk assessments to e nsure that the risk estimates are based on the best available information.

Cumulative Risk Assessment

The Food Quality Protection Act (FQPA) requires the Agency to consider the cumulative risks of chemicals sharing a common mechanism of toxicity. The A gency determined that there was insufficient evidence to suggest fenhexamid shares a common mechanism of toxicity with other

chemical 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 Program 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/

.

### Fenhexamid Registration Review Human Health Scoping Document

Page 11 of 22 Data Requirements

The following toxicity studies are required to support the registration review of fenhexamid:

Toxicology Immunotoxicity study (870. 7800)

Residue Chemistry

No outstanding residue chemistry data are required to support the registration review of

fenhexamid.

Occupational/ Residential Exposure

None

References

Table 1. HED Memoranda Relevant to Registration Review

Author Barcode/TXR # Date Title

John

Redden D329137 6/ 14/ 2006 Human Health Risk

Assessment for Fenhexamid

– IR

- 4 Tolerance Requests on

Cilantro (Transplant / Greenhouse), Non

- Bell Pepper (Transplant) and Pomegranate (Post

- Harvest).

G. Jeffrey

Herndon D253792 03/11/1999 Fenhexamid. Results of the

HED Metabolism Assessment Review Committee Meeting

Held on 3/2/99.

Breann

Hanson D347171 12/05/2007 Fenhexamid. Chronic Dietary Exposure Assessment for the Interregional Research Project No. 4 (IR

- 4) Petition Proposing

Tolerances for Residues of Fenhexamid on Asparagus (PP# 7E7187).

Breann

Hanson D340304 12/31/2007 Fenhexamid: Human Health

Risk Assessment for a Proposed Section 3 Registration for Use on Asparagus

### Fenhexamid Registration Review Human Health Scoping Document

Page 12 of 22 Table 1. HED Memoranda Relevant to Registration Review

Author Barcode/TXR # Date Title

Brenda Tarplee TXR No. 0051704 03/26/2003 Fenhexamid: 2 nd 

### Report of the

Hazard Identification

Assessment Review

Committee G. Jeffrey

Herndon D244844 and D249061 03/25/1999 PP# 7F04890. Fenhexamid on Grapes and Strawberries.

Review of Residue Data and Analytical Methodology.

MRID# 443467

- 56 thru

- 67

443665

- 08 thru

- 12

445140

- 02 thru

- 04 Rury, K TXR No. 01/2 9 /2013 Fenhexamid: Summary of Hazard and Science Policy of January 24, 2013:

Recommendations on the Need for a Subchronic Neurotoxicity

and 90

- day Inhalation Toxicity

Studies

Mark I.

Dow D328715 05/17/2006 Fenhexamid: Exposure/Risk

Assessment for Fenhexamid

Used as Post

- Harvest Treatment of Pomegranate Fruit, Cilantro, and Non

- Bell Pepper Transplants Margarita

Collantes D292433 08/01/03 Occupational and Residential Exposure Assessment for Section 3 Registration of Fenhexamid on Stone Fruits, Kiwis, Fruiting Vegetables, Cucumbers, Leafy Greens

Attachments

Attachment 1. Chemical Identity Attachment 2. Toxicity Profile Tables Attachment 3. Endpoint Tables

Attachment 4. Fenhexamid International Residue Limits Table

Attachment 1

### Fenhexamid Registration Review Human Health Scoping Document

Page 13 of 22 Table A1.1. Fenhexamid Nomenclature.

Compound

Common name Fenhexamid

Company experimental name KBR 2738

IUPAC name 2,3

- dichloro

- 4

- (1

- methylcyclohexyl

- carbonylamine)

- phenol

CAS name N

- (2,3

- dichloro

- 4

- hydroxyphenyl)

- 1

- methyl

- cyclohexanecarboxamide

CAS registry number 126833

- 17

- 8

End

- use products (EP) ELEVATE 50 WDG Fungicide

Table A 1.2. Physicochemical Properties of the Technical Grade Fenhexamid

Parameter Value Reference

Melting point/range 153 o C Fenhexamid: Pesticide Fact Sheet (May 20, 1999)

Fenhexamid (KBR 2738)

- a Botryticide from a New Chemical Class,

Pflanzenschutz

Nachrichten Bayer 52/1999, 2 pH 8.3 in 1% solution of water

Density 1.34 g/mL @ 20 o C
Water solubility ( 20 C) 20 mg/L
Solvent solubility (mg/L at 20 C) dichloromethane: 31000,

2

- propanol: 91000,

n

- hexane: < 100,

Toluene: 5700
Vapor pressure at 25 C 7x10 - 9 Torr

Dissociation constant (pK

a ) 7.3

Octanol /water partition coefficient Log(K OW ) 3.51 (pH 7, 20 o C )

UV/visible absorption
spectrum 245 nm and 290 nm (wavelengths of maximum absorption)

### Fenhexamid Registration Review Human Health Scoping Document

Page 14 of 22 Attachment 2

Table A 2. 1. Acute Toxicity of Fenhexamid Technical 1

GDLN STUDY TYPE MRID RESULTS TOX CATEGORY

81

- 1 Acute Oral

Rats 44346769 M: LD 50 >5000 mg/kg

F: LD 50 >5000 mg/kg IV

81

- 2 Acute Dermal

Rats 44346770 M: LD 50 >5000 mg/kg

F: LD 50 >5000 mg/kg IV

81

- 3 Acute Inhalation

Rats 44366513 DUST

M: LC 50 >5.057 mg/L

F: LC 50 >5.057 mg/L DUST

IV

81

- 4 Primary Eye Irritation

Rabbits 44346771 Not an eye irritant IV

81

- 5 Primary Skin Irritation

Rabbits 44346771 Not a dermal irritant IV

81

- 6 Dermal Sensitization

Guinea Pigs 44346772

44346773 Not a dermal sensitizer N/A

1 All studies were conducted on technical grade fenhexamid, 95.5% purity.

Table A 2. 2. Toxicity Profile of Fenhexamid Technical

Guideline No./ Study Type MRID No. (year)/

Classification/Doses Results

28

- Day Oral (Gavage)

– Rat (Range

- Finding) 44346774(1995)
Acceptable

0, 100, 300, 1000 mg/kg Male : NOAEL = 1000 mg/kg/day (HDT)
LOAEL = Not established

Female: NOAEL = 1000 mg/kg/day (HDT)

LOAEL = Not established

870.3100

13

- Week Feeding

- Rat 44346775 (1994)
Acceptable/guideline

0, 2500, 5000, 10,000, 20,000 ppm

0, 202, 415, 904, 1904 mg/kg/day (M)

0, 270, 549, 1132, 2824 mg/kg/day (F) Male: NOAEL = 415 mg/kg/day LOAEL = 904 mg/kg/day, based on decreased body weight and body weight gain; increased food consumption; decreased food efficiency; and
increased serum alanine aminotransferase.

Female: NOAEL = 1132 mg/kg/day LOAEL = 2824 mg/kg/day, based on increased food consumption; decreased food efficiency; decreased liver weights; and mild histopathological effects on the liver

870.3100

14

- Week Feeding

- Mouse (Range

- Finding) 44346778 (1993) Acceptable/guideline

0, 100, 100, 10,000,

ppm
0, 26.5, 266.5, 3283.5 mg/kg (M) 0, 51.6, 453.9, 5151.1 NOAEL = 267/454 mg/kg/day (M/F) LOAEL = 3284/5151 mg/kg/day (M/F), based on increased water consumption, increased serum creatinine, increased cholesterol and bilirubin decreased kidney weights, histopathological changes in the kidney. Additionally, increased food consumption; decreased food efficiency; and decreased glycogen in hepatocytes (M).

### Fenhexamid Registration Review Human Health Scoping Document

Page 15 of 22 Table A 2. 2. Toxicity Profile of Fenhexamid Technical

Guideline No./ Study Type MRID No. (year)/

Classification/Doses Results

mg/kg (F)

870.3150

13

- Week Feeding

- Dog 44346779 (1995)
Acceptable/guideline

0, 34, 239, 1748 mg/kg (M)

0, 37, 261, 1866 mg/kg (M) Male: NOAEL = 34 mg/kg/day LOAEL = 239 mg/kg/day, based on increased
Heinz bodies

Female: NOAEL = 37 mg/kg/day LOAEL = 261 mg/kg/day, based on increased
Heinz bodies

870.3200

21

- Day Dermal Toxicity

- Rabbit 44346780 (1995)
Acceptable/guideline
0, 1000 mg/kg/day (M & F) NOAEL ( systemic) = 1000 mg/kg/day (HDT) LOAEL ( systemic ) = Not established

NOAEL ( derma l) = 1000 mg/kg/day (HDT) LOAEL ( dermal ) = Not established

5

- Day Inhalation

– Rat
DUST (Range

- Finding) 44366514 (1996)
Acceptable

0, 11.8, 97.7, 1092.6 mg/m 3 (0, 0. 012, 0.098, 1.093 mg/L (M

& F) NOAEL = 0.098 mg/L LOAEL = 1.093 mg/L (M & F)

870.3465

21/28

- Day Inhalation HASPOC has waived this study (Rury, 2013)

.

870.4100a

2

- Year Chronic Toxicity/ Carcinogenicity

- Rat 44346806 (1996) Acceptable/guideline

0, 500, 5000, 20,000

ppm 0, 28, 292, 1280 mg/kg/day (M)

0, 40, 415, 2067 mg/kg/day (F) Male: NOAEL = 28 mg/kg/day LOAEL = 292 mg/kg/day, based on increased splenic extramedullary hematopoietic & increased cecal mucosal hyperplasia

Female: NOAEL = 40 mg/kg/day LOAEL = 415 mg/kg/day, based on decreased body weight (only after 60 weeks), decreased body weight gain (only after 39 weeks), decreased food efficiency, and bone marrow hyperplasia.

No evidence of carcinogenicity in either sex.

870.4100b

2

- Year Carcinogenicity

- Mouse 44346805(1996) Acceptable/guideline

0, 800, 2400, 7000

ppm 0, 247.4, 807.4, 2354.8 mg/kg/day (M)

0, 364.8, 1054.5, 3178.2 mg/kg/day (F) Male: NOAEL = 247 mg/kg/day LOAEL = 807.4 mg/kg/day, based on decreased kidney weights, & decreases in sex

- specific vacuolation of the proximal tubules in the kidneys.

Female: NOAEL = 1054.5 mg/kg/day LOAEL = 3178.2 mg/kg/day, based on increased water consumption, decreased kidney weights, & renal histopathology (increased incidence of basophilic cortical tubules)

No e vidence of carcinogenicity in either sex.

870.4100b

1

- Year Chronic Feeding

- Dog 44346804(1996)
Acceptable/guideline

0, 500, 3500, 25,000

ppm (0, 17.4, 124.3, 917.8 mg/kg/day M) NOAEL = 17.4/19.2 mg/kg/day

LOAEL = 124.3/132.7 mg/kg/day, based on decreased RBCs, Hb and Hct and increased Heinz bodies (M & F) & increased adrenal weight (F), and presence of intracytoplasmic vacuoles in the adrenal cortex (M).

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Page 16 of 22 Table A 2. 2. Toxicity Profile of Fenhexamid Technical

Guideline No./ Study Type MRID No. (year)/

Classification/Doses Results

(0, 19.2,132.7, 947.1 mg/kg/day F)

870.3700a
Developmental Toxicity

- Rat 44346781 (1994) Acceptable/guideline
0,1044 mg/kg/day Maternal: NOAEL = <1044 mg/kg/day



### LOAEL = 1044 mg/kg/day (HDT), based on decreased body weight gain (

- 12%) during gestation days 6

- 16 & decreased food consumption (10%)

Developmental: NOAEL = 1044 mg/kg/day (HDT)
LOAEL = Not established

870.3700b Developmental Toxicity

- Rabbit 44346801(1995)
Acceptable/guideline 0, 100, 300, 1000 mg/kg/day Maternal: NOAEL = 100 mg/kg/day LOAEL = 300 mg/kg/day, based on alterations of excretory products (discolored urine & small scybala) Developmental: NOAEL = 300 mg/kg/day LOAEL = 1000 mg/kg/day based on decreased male fetal body weight & evidence of delayed
ossification

870.3800

2

- Generation Reproductive Toxicity

- Rat 44346803 (1996) Acceptable/guideline

0, 100, 500, 5000, 20,000 ppm

0, 7.6, 38.2, 406, 1814 mg/kg/day (M)

0, 9.0, 44.8, 477, 2043 mg/kg/day (F) Parental/Systemic:
Males: NOAEL = 38 mg/kg/day LOAEL = 406 mg/kg/day, based on increased creatinine (P gen only), increased alkaline phosphatase, decreased absolute & relative liver weights, decreased absolute & relative kidney weights

Females: NOAEL = 45 mg/kg/day LOAEL = 477 mg/kg/day, based on increased alkaline phosphatase & a small increase in GGT

Reproductive :

NOAEL = 1841/2043 mg/kg/day (M/F) (HDT)

Offspring: NOAEL = 38/45 mg/kg/day (M/F)

LOAEL = 406/477 mg/kg/day (M/F), based on
dose

- related decreased pup body weights on lactation days 7, 14, & 21 days for F 1 (6

- 11%) &
for F 2 (9

- 11%); effect is considered severe.

870.5100

Reverse Gene Mutation

– Salmonella typhimurium 44346807 (1991)
Acceptable/guideline

0, 62.5, 125, 250, 500, 1000, 2000, 5000 μg/plate +/

- S9 Non

- mutagenic (±) activation up to insoluble and cytotoxic concentrations (≥ 2000 μg/plate).

870.5300

Forward Gene Mutation

– Chinese hamster ovary (CHO)

cells 44346810 (1994)
Acceptable/guideline

0, 25, 50, 75, 100, 125, 150 μg/mL +/

- S9 Non

- mutagenic up to cytotoxic concentrations (150 μg/mL ± activation)

### Fenhexamid Registration Review Human Health Scoping Document

Page 17 of 22 Table A 2. 2. Toxicity Profile of Fenhexamid Technical

Guideline No./ Study Type MRID No. (year)/

Classification/Doses Results

870.5375

Chromosome Aberration

- CHO

cells 44346809 (1995) Acceptable/guideline

0, 6, 30, 150 μg/mL

- S9 & 0, 2, 20, 120 μg/mL +S9 with 8, 24

& 30 hr. cell harvests Non

- mutagenic up to cytotoxic concentrations (150 μg/mL

– S9; 120 μg/mL +S9)

870.5395 Micronucleus Assay

– Mice 44346811 (1993) Acceptable/guideline
0, 750 mg/kg (IP injection) & bone
marrow cell harvests at 16, 24, & 48hrs. Negative at a dose showing clinical signs of overt toxicity.

870.5550 Unscheduled DNA Synthesis

- Rat Hepatocytes 44346812 (1992) Acceptable/guideline

0, 2.5, 5.0, 10.0, 15.0, 30.0, 40.0 μg/mL Non

- genotoxic up to a cytotoxic concentration
(40.0 μg/mL).

870.6200a Acute Neurotoxicity

- Rat 44346813 (1996)
Acceptable/guideline

0, 200, 630, 2000 mg/kg Male: NOAEL = 630 mg/kg/day LOAEL = 2000 mg/kg/day (HDT), based on lower body temperature.

Female: NOAEL = 2000 mg/kg/day (HDT)

LOAEL = Not established

870.6200b
90

- Day Neurotoxicity Screening Battery

- Rat HASPOC waived this study (Rury, 2013).

870.7485

Metabolism

- Rat 44346814 (1996)
Acceptable/guideline Very rapidly and completely absorbed and excreted (<48 hours). Pronounced enterohepatic circulation. Metabolite in bile was glucuronide. Major route of excretion was feces (mostly parent); lesser amounts in urine (mostly glucuronide).

870.7600 Dermal Absorption

– Rat 44346815(1997)
Acceptable/guideline At 10 hours, mean dermal absorption was 20% (low dose group)

870.7800 Immunotoxicity Not available

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Page 18 of 22 Attachment 3

Table A 3. 1. Summary of Toxicological Doses and Endpoints for Fenhexamid for Use in the Dietary and Non

Occupational Human Health Risk Assessments

Exposure

Scenario Point of

Departure Uncertainty/

FQPA Safety

Factors RfD/PAD Study and Toxicological Effects

Acute Dietary (General Population including infants and children) Not selected. No appropriate toxicological endpoint attributable to a single exposure was identified in the

available toxicology studies.

Chronic Dietary (All populations) NOAEL = 17 mg ai/kg/day

UF = 100

Chronic RfD = 0.17 mg/kg/day UF A 10X

UF H 10X

FQPA 1X

Total UF 100 cRfD = .17

mg/kg/day

cPAD = 0.17 mg/kg/day 1

- Year Feeding Study (dog)

MRID 44346804 LOAEL = 124 mg/kg/day, based on decreased RBC counts, hemoglobin and hematocrit and increased Heinz bodies in males and females; increased adrenal weights and intracy toplasmic

vacuoles in adrenal cortex in females

Short

- Term (1

- 30 days),

Intermediate

- Term (1

- 6 months) and Long

Term (>6 months)

Dermal and Inhalation Not selected. There are no residential exposures (see TXR NO. 013258)

.

Cancer (oral) Classification: “Not likely to be Carcinogenic to Humans” based on the absence of significant tumor increases in two adequate rodent carcinogenicity studies.
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. UF A = extrapolation from animal to human (interspecies). 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. MOE = margin of exposure. LOC = level of concern. PAD = population adjusted dose (a = acute, c = chronic). RfD = reference dose, MOE = margin of exposure, LOC = level of concern

### Fenhexamid Registration Review Human Health Scoping Document

Page 19 of 22 Table A 3. 2. Summary of Toxicological Doses and Endpoints for Fenhexamid for Use in the Occupational

Human Health Risk Assessments

Exposure

Scenario Point of

Departure Uncertainty/

FQPA Safety

Factors RfD/PAD Study and Toxicological Effects

Short

- Term (1

- 30 days) and

Intermediate

- Term (1

- 6 months)

Dermal NOAEL = 1000 mg ai/kg/day UF A = 10

UF H = 10 FQPA SF = 1X Residential

MOE = NA

Occupational

MOE = 100 21

- Day Dermal

- Rabbit.

MRID 44346780 LOAEL = 1000 mg/kg/day

Consistent with the findings of the developmental toxicity study in rabbits (MRID 44346801) showing decreased body weight gain and food consumption at LOAEL of 300 mg/kg/day; the NOAEL in this study is 100 mg/kg/day. The dermal equivalent dose, using 20% dermal absorption factor, the NOAEL would be 500 mg/kg/day and the

LOAEL would be 1500 mg/kg/day.

Long

- Term Dermal (>6 months) None Residential

MOE = NA

Occupational

MOE = NA Not selected. It was determined that no long

term exposure would occur (see TXR NO. 013258).

Short

- Term (1

- 30 days),

Intermediate

- Term (1

- 6 months) and

Inhalation None Residential

MOE = NA

Occupational

MOE = NA Not selected. Based on low acute toxicity, the composition of the formulated product, and the application methods, HED

determined that there is a minimal concern for potential inhalation exposure (see TXR

NO. 0051704 )

. HASPOC reaffirmed this

decision (Rur y, 2013).

Long

- Term (>6 months)

Inhalation None Residential

MOE = NA

Occupational

MOE = NA Not selected. It was determined that no long

term exposure would occur (see TXR NO. 013258).

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 effec t level. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). 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. MOE = margin of exposure. LOC = level of concern. PAD = population adjusted dose (a = acute, c = chronic). RfD = reference dose, MOE = margin of exposure, LOC = level of concern. Dermal absorption factor = 20% (see MRID 44346815)

### Fenhexamid Registration Review Human Health Scoping Document

Page 20 of 22 Attachment 4. Fenhexamid International Residue Limits Table

Table A 4.1. Summary of US and International Tolerances and Maximum Residue Limits for all registered

commodities Residue Definition :

US Canada Mexico 1 Codex 2

40 CFR 180.553 fenhexamid (N

- 2,3

- dichloro

- 4

- hydroxyphenyl)

- 1

- methyl cyclohexanecarboxamide) N

- 2,3

- dichloro

- 4

- hydroxyphenyl)

- 1

- methyl cyclohexanecarboxamide Fenhexamid

The residue is fat

soluble.

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

US Canada Mexico 1 Codex 2

Almond, hulls 2.0 2

Almond 0.02 0.02 almond nuts 0.02 (*) Asparagus 0.02

Bushberry subgroup 13B 5.0 4.0 blueberries, currant, elderberries, gooseberries,

huckleberries 5.0 bilberry, blueberries, currants, black, red, white, elderberry, gooseberry

Caneberry subgroup 13A 20.0 20 blackberries, loganberries, raspberries 15 blackberries, dewberries (including boysenberry and loganberry), raspberry
Cilantro, leaves 30.0

Cucumber 2.0 1.0

Fruit, stone, group 12,
except plum, prune, fresh, postharvest 10.0 6.0 apricots, cherries, nectarines, peaches

0.5 plums 7.0 cherries 10 apricots, nectarine, peach 1.0 plums (including prunes) Ginseng 0.3 0.3 ginseng roots Grape 4.0 4.0 15.0

Grape, raisin 6.0 6.0 raisins 25.0 dried grapes (=currants, raisins and sultanas) Juneberry 5.0 5.0 Kiwifruit, postharvest 15.0 15.0 kiwifruit Leafy greens subgroup 4A, except spinach 30.0 23.0 lettuce, head, leaf lettuce 30.0 lettuce, head and

leaf Lingonberry 5.0

Pear 10 Pepper, nonbell 0.02 2.0 peppers

Pistachio 0.02 Plum, prune, dried 2.5 Plum, prune, fresh 1.5 0.5 plums 1.0 plums (including prunes) Pomegranate 2.0

Salal 5.0 Strawberry 3.0 3.0 10 Vegetable, fruiting, group 8, except nonbell pepper 2.0 1.0 tomatoes 2.0 eggplant, tomato,

peppers MRLs with No US Equivalent Edible offal (mammalian) 0.05

Gherkin 1

### Fenhexamid Registration Review Human Health Scoping Document

Page 21 of 22 Table A 4.1. Summary of US and International Tolerances and Maximum Residue Limits for all registered

commodities Residue Definition :

US Canada Mexico 1 Codex 2

Meat (from mammals other than marine mammals)

Milks 0.01 (*) F Squash, summer 1

Completed: M. Negussie; 01/14/2013

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

2 * = 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. MRLs indicated as proposed have not been finalized by the CCPR and the CAC.

Table A 4.2. Summary Maximum Residue Limits (Not Harmonized)

Residue Definition : US, Fenhexamid, 40 CFR 180.553 Canada Mexico 1 Codex 2

(N

- 2,3

- dichloro

- 4

- hydroxyphenyl)

- 1

- methyl cyclohexanecarboxamide) N

- 2,3

- dichloro

- 4

- hydroxyphenyl)

- 1

- methyl cyclohexanecarbox

amide Fenhexamid

The residue is fat

soluble.

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

US Canada Mexico 1 Codex 2

Bushberry subgroup 13B 5.0 4.0 blueberries,

currant, elderberries, gooseberries,

huckleberries 5.0 bilberry, blueberries, currants, black, red, white, elderberry, gooseberry

Caneberry subgroup 13A 20.0 20.0 blackberries, loganberries, raspberries 15.0 blackberries,

dewberries (including boysenberry and loganberry), raspberry

Cucumber 2.0 1.0

Fruit, stone, group 12, except plum, prune, fresh, postharvest 10.0 6.0 apricots, cherries, nectarines, peaches

0.5 plums 7.0 cherries 10.0 apricots, nectarine, peach 1.0 plums (including prunes)

Grape 4.0 4.0 15.0

Grape, raisin 6.0 6.0 raisins 25.0 dried grapes (=currants, raisins and sultanas) Leafy greens subgroup 4A, except spinach 30.0 23.0 lettuce, head,

leaf lettuce 30.0 lettuce, head

and leaf

### Fenhexamid Registration Review Human Health Scoping Document

Page 22 of 22 Table A 4.2. Summary Maximum Residue Limits (Not Harmonized)

Residue Definition : US, Fenhexamid, 40 CFR 180.553 Canada Mexico 1 Codex 2

Pepper, nonbell 0.02 2.0 peppers

Plum, prune, fresh 1.5 0.5 plums 1.0 plums (including prunes) Strawberry 3.0 3.0 10.0 Vegetable, fruiting, group 8, except nonbell pepper 2.0 1.0 tomatoes 2.0 eggplant,

tomato, peppers

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

2 * = 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. MRLs indicated as proposed have not been finalized by the CCPR and the CAC.