### UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON

, D

. C

. 20460



### MEMORANDUM

Date: 07-JAN

- 20 15 OFFI CE OF C H EMICA L SAFETY A N D P OLLlrrtON PR EVENTION



### SUBJECT: Spir odiclofen. Human Health Assessment Scoping Document in S upport of Registration Review.

PC C ode: 1248 7 1 Decision No.: 494555 Petition No.: N / A Risk Assessment Type: N / A TXRNo.: N / A MRID No.: N / A DP Barcode: 0422434 Registration No.: N / A Regulatory Action: Registration Review Scoping Document Case No.: 7443 CAS No.: 14 84 77

- 71 -8 40 CFR: § 180 .608

/ 

### FROM: Kelly Lowe
, Env ironmen ta l Scientist

, .**..- ,~** **_, ..,_** **.--** 

### T homas Blo e m ,

## Chern~**~~** . Monique M. Perron
, Sc.D.

, To xicologist

## Jf~ Risk Assessment Branch l (RAB 1 ) Health Effects Division (HE D
,**7509P L_~** 


### THROUGH: C harl es W

. Smith III
, Branch

# Chie**~~~~~:f:r--::a--­** George F. Kramer
, Ph.D.

, Senior Chemist RABl/HED (7509 P)

TO: Julia Stoke s, Chemical R ev iew Mana ge r Pesticide R e

- Eva luation Di vis ion (PRD) (7508P)

Attached is H ED ' s human health risk asse ss ment scoping docum ent for spirodiclofen to s upport Registration Review.

Pag e I of 23

### Table of Contents Executive S u mmary

........ . ............................ . .................................. :

.. .. ................ .. .. .. ............. .. .. .. .. 3 1

. 0 In troduction

. ... . .. . . ... .. .. .. ..... .. .. .. . .. .. .. .. .. . . ... . ... .. .......................... ... .. .. ................... .. .... . ........ .. .. .. .. 4 2.0 H azard Characterization/Assessment.

........................ .. .. .. ...... .. .. .. .... . ...... .. .. .. .. .. ....................... 4 3.0 Residue Chemis t ry

............... .. .................... .. .. .. .. .. .. .. . .. .. .. ................... . ...... .. .. ... .. .. ................. ... 6 

### 4.0 Dietary Exposure

. .. .... ... . .. .. .. .. . .. .. . .. .. .. .. .. .. .. .. . ... ...................... . .... .. .. .. ... .. .. .. .. ... .. .. ..... . ........... .. .. 7 5.0 Residential Exposu r e

..... . ................................... . .. . .. .. .. .. .. .. . :

.. ...................................... .. .... .. .. .. 8 6.0 Aggregate Risk Assessmen t..

.. . .. .. .. .. .. .. .. . . , .. . .. ..................................... .. .. .. .. .. .. .. ...... .. .... .. ... .. . . .. 8 7.0 Occupational Exposure

........ . ...................................... .. .. .. .. .. .. .. ,. .... .. ... .. ...................... . ............ 9 8.0 Public Health and Pesticide Epidemio l ogy Data

......................................... . ........... .. .. .. .. .. .... 10 9.0 To l erance Assessment and I nternational Harmonization

.. .. .. .. .. .. .. .. .. .. . .. .. .... ...... .. .. .. ............. 10 10.0 Environmenta l Justice

................ .. ..... .. .. .. .. .. ..... .. ...... .. .. .. . .. ......................................... .. ........ 10 11.0 Cumula t ive

.. .. .. ..... .. ..... .. ............ ... . .. .. .. . ... .... . ..... . ................... . .................... . ..... .. .. .. .. .. .. ... .. ... 10 12.0 Human Studies

..................... . .................. .. ........... . .. .. .......... .. .. .. ..... .. .. .. ............ . ............ . ...... 1 1 13

. 0 Risk Assessment Updates and Da t a Deficiencies

.. .. ............................................. . .............. 

### 11 1 4 .0 References

.. .. .. . .. .. .. . .. .. .. . .. .. .. . .. ......... . ............................................... . ...................... .. ......... . .. 12 Attachment 

### 1 : Chemical I den t ity Tables

................... .. ................... - .. .. .. .. .. .. .. .. .. . ... .. .. .. .. .. .. .. .. .... .. . 

### 14 Attachment 2: Spirodiclofen Acute, Subchronic, and Chronic Toxicity Profile

. .. .. .. .. ........ .. .. .. .. 

### 15 A tt achment 3 : Summary of Toxico l og i ca l D oses and E n dpoints for Spirodiclofen (from 2009 Risk Assessment)

.................................... . .. . ....... . .... . .. .. . .. ... . .. . ... . ... .. .. . .. .. .. .. ... . .. .. ... . ... . ... . .... .. .. . .... .. 19 A tt achment 4: Summary of Residues of Concern for Spirodiclofen

........................................... 20 Attachment 5: Summary of Registered Uses for Spirodiclofen

..... .. .. .. ... .. . .. .. .. ... .. .. .. .. .. .. .. .... .. .. ... 2 1 Attachmen t 6: Spirodiclofen In t ernat i ona l Res i due Lim i t Stat u s Sheet.

........ .. .. .. .. .. .. .. ... .. .. ... .. ... 22

Page 2 of23Spirodiclofen Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________ _________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ ______ _____________________________________________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ ______ _____________________________________________________________________________________________________________________________ ____________________________________________________________________

Page 3 of 23 

### Executive Summary

HED has prepared a scoping document to support Registration Review of the acaricide spirodiclofen (3

- (2,4

- dichlorophenyl)

- 2

- oxo

- 1

- oxaspiro[4.5]dec

- 3

- en

- 4

- yl 2,2

- dimethylbutanoate)

. Spirodiclofen is a tetronic acid acaricide, and acts by interfering with mite development. It is active by contact to mite eggs, all nymphal stages, and adult females (adult males are not affected).

Spirodiclofen is formulated as a suspension

- concentrate (SC) formulation in one end

- use product [ Envidor ® 

### 2SC Miticide [2 pounds (lbs) active ingredient (ai)/gallon; EPA Reg. No. 264

- 831]

, and is currently regist ered for use on a variety of crops such as citrus, fruit trees, grapes, hops, pome fruits, stone fr uits, tree nuts, and Christmas tree p lantings

.

The most recent human health risk assessments were performed for uses on bushberries and tropical fruits a 

### ; however, the petitions for these uses were subsequently withdrawn. The most recent human health risk assessment that covers currently registered uses for spirodiclofen was performed in 20 09 , and was for the use of spirodiclofen on tree fruits (Memo, T. Bloem et al.

, 0 6

- OCT

- 20 09 ; D 361071 ).

HED has evaluated the status of th e human health asse ssments for spirodiclofen to determine whether sufficient data are available

, and whether any updates are needed to support Registration Review. HED has considered all available data and human health risk assessments for spirodiclofen with respect to its toxicity, exposure, and usage databases, and the most updated Agency science policy and risk assessment methodologies to determine the scope of work necessary to support Registration Review.

The toxicity database for spirodiclofen is complete as required by the 2007 revised 40 CFR Toxicology Data Requirements. No additional toxicological studies are currently required. As part of Registration Review, t he inhalation endpoint used for spirodiclofen risk assessment will be updated to re flect current HED policy.

The residue chemistry database for spirodiclofen is adequate to support current Registration Review data requirements. Adequate metabolism (crops, livestock, and rotational crops), storage stability, magnitude of the residue, an d processing data are available to support the registered uses. Adequate methods are available for enforcement of the currently established tolerances. No additional residue chemistry data are required to support the current registrations.

The dietary

- exposure database for spirodiclofen is adequate to support current registration requirements. As part of Registration Review, a revised dietary

- exposure analysis may be required to reflect the most recent dietary

- exposure models and potential ly revised E DWCs (specifically, use of PRZM

- GW).

There are no proposed or current registrations for products containing spirodiclofen that allow residential use. Therefore, residential handler and post

- application exposure assessments will not be needed during Regis tration Review. The need for spray drift and volatilization risk
assessment s for spirodiclofen will be examined during Registration Review.

a Memo, J. Tyler et al., 11

- NOV

- 2011, D386201 (Tropical Fruit Risk Assessment); Memo, T. Bloem et al., 28

- JUL

2010, D371469 (Bushberry Risk Assessment).Spirodiclofen Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________ _________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ ______ _____________________________________________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ ______ _____________________________________________________________________________________________________________________________ ____________________________________________________________________

Page 4 of 23 

### The occupational exposure database is adequate to support the Registration Review process for spirodiclofen . The most recent occupational handler and post

- application exposure assessments

are not reflective of maximum application rates or current exposure policies and data, but did not identify risks of concern. D uring Registration Review, updated occupational handl er inhalation assessments will be conducted to reflect all currently registered uses and maximum application rates, using current occupational and residential exposure (ORE) policies and updated inhalation toxicological points of departure ( PODs )

.

1.0 Introduction

Spirodiclofen is a tetronic acid a caricide and acts by interfering with mite development. It is active by contact to mite eggs, all nymphal stages, and adult females (adult males are not affected). Spirodiclofen is formulated as a SC formul ation in one end

- use product [Envidor ® 

### 2 SC Miticide ( 2 lbs ai/gallon; EPA Reg. No. 264

- 831 ) ], and is currently registered for use on a variety of crops such as citrus, fruit trees, grapes, hops, pome fruits, stone fruits, tree nuts, and Christmas tree plan tings. The most recent risk assessments were performed for uses on bushberries and tropical fruits b 

### ; however, the petitions for these uses were subsequently withdrawn. The most recent human health risk assessment that covers currently registered uses for spirodiclofen was performed in 2009, and was for the use of spir odiclofen on tree fruits (Memo, T. Bloem et al.

, 0 6

- OCT

- 2009; D361071 ).

2.0 Hazard Characterization/Assessment

Following oral administration, radiolabeled spirodiclofen was rapidly and ext ensively absorbed from the gastrointestinal tract into the systemic circulation. Based on the radioactivity quantified at 48 hours, females absorbed a greater fraction of approximately 74% versus 57

- 62% estimated for males. Spirodiclofen underwent ex tens ive metabolism with both urine and feces as major routes of elimi nation. Female rats metabolized spirodiclofen to a urinary enol metabolite more extensively than did males (39.65

- 52.42% versus 4.88

- 5.41% of the administered dose, respectively). Parent co mpound was detected only in small quantities in the feces (probably reflecting unabsorbed compound) and was not detected in urine or bile. Excretion was approximately 90% complete at 48 hours post dosing. Results of biliary excretion experiments showed t hat approximately 11% of the administered dose appeared in the bile as biotransformation products. There was no evidence of accumulation in any specific organs or tissues up to 48 hours post

- dose

. Spirodiclofen is classified as having low acute toxicity via the oral (Toxicity Category III), dermal (Toxicity Category III), and inhalation (Toxicity Category IV) routes. It is not an eye or dermal irritant and is classified as a dermal sensitizer.

T he effects observed following repeated oral exposures to spirodiclofen have been remarkably consistent across different studies and species tested. The primary target organs identified are the adrenal glands in both sexes and testes in males. Increased c ytoplasmic vacuolation of the adrenal cortex has been consistently observed across different subchronic and chronic studies with spirodiclofen in both sexes of rats, mice, and dogs. The dog was the most sensitive species and, at least in rat and dog studi es, females appear to be the more sensitive sex. Effects on the adrenal glands generally coincided with increased adrenal weight. Other organs with

b Memo, J. Tyler et al., 11

- NOV

- 2011, D386201 (Tropical Fruit Risk Assessment); Memo, T. Bloem et al ., 28

- JUL

2010, D371469 (Bushberry Risk Assessment).Spirodiclofen Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________ _________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ ______ _____________________________________________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ ______ _____________________________________________________________________________________________________________________________ ____________________________________________________________________

Page 5 of 23 

### histopathology findings reported in male dogs included the testes ( vacuolation and hypertrophy/activation of Leydig cells, tubular degeneration) , epididymis ( degeneration and/or immaturity of germinal epithelium, oligospermia

, and aspermia ), prostate (immaturity signs), and thymus ( atrophy) . Increased liver weights were also reported in male dogs along with d ecreases in prostate weights. Other effects reported in chronic studies include decreases in cholesterol and triglycerides (rats), decreased body weights (rats), increased alkaline phosphatase levels, increased vacuolated jejunum enterocytes (rats), and i ncreased incidence of Leydig cell hyperplasia (rats and mice).

There was evidence of increased quantitative susceptibility in the rat developmental toxicity study, where an increased incidence of slight dilatation of the renal pelvis was observed in fetu ses at the limit dose (1000 mg/kg/day) in the absence of maternal toxicity. Concern is low since t he effect was slight, only seen at the limit dose, occurred without statistical significance, and did not display a clear dose response. There were no devel opmental effects seen in the rabbit developmental toxicity study while maternal toxicity was evidenced as body weight decrements. In the two

- generation reproduction toxicity study, offspring effects (body weight decrements) occurred in the presence of par ental effects. Additional effects observed at higher doses included delayed sexual maturation, increased severity of ovarian luteal cell vacuolation/degeneration

, decreased testicular spermatid and epididymal sperm counts, and atrophy of the testes, epidi dymides, prostate, and seminal vesicles.

S pirodiclofen is not considered to be a neurotoxic compound based on acute, subchronic, and developmental neurotoxicity studies

. In a dermal toxicity study, spirodiclofen did not exhibit toxicity up to the limit dose (1000 mg/kg/day). A dermal absorption factor of 2% was previously estimated based on the results of two dermal absorption studies in monkeys.

In a recently submitted immunotoxicity study in mice (MRID 49072601), there was no evidence of immunotoxicity up the highest dose tested (1216 mg/kg/day).

The Cancer Assessment Review Committee (CARC) classified spirodiclofen as “likely to be carcinogenic to humans” by the ora l route based on evidence of testes Leydig cell adenomas in male rats, uterine adenomas and/or adenocarcinoma in female rats, and liver tumors in mice. There is no evidence of genotoxicity from spirodiclofen

. The toxicology database for spirodiclofen is complete except for a subchronic inhalation study that is required in accordance with the current 40 CFR Part 158 Toxicology Data Requirements; however the Hazard and Science Policy Council (HASPOC) concluded based on a weight

- of

evidence approach that the study is not required at this time (K. Rury; 03

- MAR

- 2014; TXR #0056904). Therefore, the database is considered complete to support existing registrations and R egistration R eview.

The endpoints from the most recent human health risk assessment for spirod iclofen ( Memo, T. Bloem et al. , 06

- OCT

- 2009; D361071 ) can be found in Attachment 3 . Since the last risk assessment, the study classification of the 28

- day dermal toxicity study has been updated from unacceptable to acceptable/non

- guideline ( Memo, M. Perron; 07

- OCT

- 2014; D423215). As a result, a quantitative dermal assessment is no longer required for spirodiclofen assessments since no effects were seen in the dermal toxicity study up to the limit dose

, and although increased quantitative susceptib ility was seen in the rat developmental toxicity study, the developmentalSpirodiclofen Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________ _________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ ______ _____________________________________________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ ______ _____________________________________________________________________________________________________________________________ ____________________________________________________________________

Page 6 of 23 

### effect was slight and only seen at the limit dose. An endpoint for a long

- term inhalation scenario also would not be needed because long

- term exposures are not expected based on the use pattern for spirodiclofen. Consequently, selection of one endpoint to assess short

- and intermediate

- term inhalation scenarios would be appropriate.

Conclusions: The toxicity database for spirodiclofen is complete as required by the 2007 revised 40 CFR Toxicology Data Requirements. No additional toxicological studies are currently required. As part of Registration Review, the inhalation endpoint used for spirodiclofen risk assessment will be updated to reflect current HED policy

. This change is n ot expected to significantly alter the risk conclusions for spirodiclofen

, but will significantly simplify the
assessment

.

3.0 Residue Chemistry

Spirodiclofen (Envidor 2SC Miticide; EPA Reg. No. 264

- 831) is currently registered for foliar application s to the following food/feed crops: avocado, black sapote, canistel, grape, hops, mamey sapote, mango, papaya, pistachio, sapodilla, star apple, citrus fruit group 10, pome fruit group 11, stone fruit group 12, and tree nut group 14. The following paragra phs are a summary of the residue chemistry database.

Application Scenarios for Food/Feed Crops: Envidor 2SC Miticide (EPA Reg. No. 264

- 831; 2 lb ai/gallon) is the only currently registered spirodiclofen end

- use product. The current label permits folia r application s to the registered crops at rates of 0.31

- 0.53 lb ai/acre/season and indicates that th o rough coverage of plant parts is required for pest control ( pre

- harvest interval ( PHI ) = 2

- 14 days). The current labeled instructions are as reviewed/reco mmended by HED.

Nature/Magnitude of the Residue

- Crops: Based on the results of (1) the citrus, grape, and apple metabolism studies ( Memo, M Clock

- Rust et al. , 22

- J UN

- 2005, D285047), (2) the apple, grape, and orange processing studies ( Memo, T. Bloem, 22

- J UN

- 2005, D341847; Memo, T. Bloem, 24

- J UN

- 2009, D359773 ; and Memo, T. Bloem, 20

- J UN

- 2011, D390192 ), and (3) conclusions relating to the residues in hops ( Memo, M. Sahafeyan, 3

- J AN

- 2008, D346710)

, HED concluded that the residues of concern in the currently

- registered crops are either parent or parent + BAJ2510 (see Attachment 4). HED notes that BAJ 2510 is only a residue of concern in the processed commodities of grape, citrus fruit, stone fruit, berry (CG 13), and tropical fruit. No additional cr op metabolism data are required to support the registered crops.

Adequate field trial data have been submitted to support the current registrations with the currently established tolerances, excluding almond hull, as recommended by HED; the almond hull tolerance should be adjusted from 20.0 ppm to 20 ppm. No additional magnitude of the residue data or supporting data are required to support the registered uses.

Nature/Magnitud e of the Residue

- Poultry: The petitioner has not submitted information concerning the nature/magnitude of the residue in poultry

, and these data are not required as none of the registered crops are significant poultry feed commodities (Table 1: Feedstu ff (June

- 2008)).

Nature/Magnitude of the Residue

- Ruminants: Based on adequate goat metabolism and cattle feeding studies, HED concluded that the residues of concern in ruminants, for purposes of tolerance enforcement and risk assessment, are spirodic lofen and BAJ 2510 (see Attachment 4 ; Memo, M Clock

- Rust et al. , 22

- J UN

- 2005, D285047 ). No additional ruminant metabolism data are required to support the registered uses.Spirodiclofen Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________ _________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ ______ _____________________________________________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ ______ _____________________________________________________________________________________________________________________________ ____________________________________________________________________

Page 7 of 23 

### The currently established cattle, goat, horse, sheep, and milk tolerances, exclu ding the meat byproduct tolerances, are as recommended by HED

, and are based on an adequate cattle feeding study and the cattle maximum theoretical dietary burden (MTDB); the meat byproduct tolerance should be adjusted from 0.1 ppm to 0.10 ppm. No additio nal magnitude of the residue data are required to support the registered uses. Tolerances in/on hog are not required as none of the registered crops are significant hog feed commodities (Table 1: Feedstuff (June

- 2008)).

Analytical Enforcement Methods: HED determined that the Bayer analytical method 109351 is appropriate for enforcement of the currently established tolerances. This method has been for warded to the Food and Drug Administration (FDA) for inclusion in the Pesticide Analytical Manual (PAM ; Memo, T. Bloem, 23

- SEP

- 2009, D368434 ).

Conclusions : The residue chemistry database for spirodiclofen is adequate to support current Registration Review data requirements. Adequate metabolism (crops, livestock, and rotational crops), storage stabilit y, magnitude of the residue, and processing data are available to support the registered uses. Adequate methods are available for enforcement of the currently established tolerances. No additional residue chemistry data are required to support the curren t registrations. HED notes that the currently established almond hull tolerance should be altered from 20.0 ppm to 20 ppm and the currently established meat byproduct (cattle, goat, horse, sheep) tolerance should be altered from 0.1 ppm to 0. 10 ppm.

4.0 Dietary Exposure

The most recent dietary

- exposure analysis was conducted in 2009 and used the Dietary Exposure Evaluation Model

- Food Consumption Intake Database (DEEM

- FCID, ver. 2.03) which incorporated consumption data from United States Departmen t of Agriculture (USDA) Continuing Survey of Food Intake by Individuals (CSFII; 1994

- 1996 and 1998; D363344, T. Bloem, 23

- S EP

- 2009).

An acute dietary risk assessment was not conducted as an endpoint attributable to a single dose was not identified

. The chronic and cancer analyses were refined using field trial data, experimentally determined processing factors, percent crop treated estimates, and new use percent crop treated estimates (hop, pome fruit, stone fruit, grape, and citrus). T he resulting chr onic risk estimates (food and water) were ≤3.3% the cPAD and are not of concern to HED (infants <1 year old were the most highly exposed population).

The cancer risk estimate (food and water) for the U.S. population was 3 x 10

- 6



### . The major contributors to the cancer analysis were hop s (40%; assumes 100% transfer of residues from hop s to beer; spirodiclofen Log K OW 

### = 5.83), water (19%; 87% of the basin cropped and 100% crop treated), and orange (17%; default processing factors were assumed ). It is noted that the petitioner has subsequently submitted an adequate orange processing study

, which will allow for refinement of the orange residue esti mates (D285249, T. Bloem, 18

- APR

- 2005; D390192, T. Bloem, 20

- JUN

- 2011).

HED notes that the 2009 chronic and cancer dietary assessments did not incorporate ground water estimated drinking water concentrations (EDWCs) modeled using the Pesticide Root Zone Model for GroundWater (PRZM

- GW). The impacts of using this model to estimate ground
wate r concentrations of spirodiclofen will need to be considered during Registration Review.Spirodiclofen Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________ _________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ ______ _____________________________________________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ ______ _____________________________________________________________________________________________________________________________ ____________________________________________________________________

Page 8 of 23 

### Conclusions: The dietary

- exposure database is adequate to support current registration requirements. As part of Registration Review, a revised dietary exposure analysis may be required to reflect the most recent dietary

- exposure models and potentially revised EDWCs (specifically, use of PRZM

- GW).

5.0 Residential Exposure

There are no registered or proposed spirodiclofen products that allow residential use; therefore, a quantitative residential exposure assessment was not conducted.

Spray Drift and Volatilization : Residential bystander exposures resulting from off

- site transport (e.g., spray drift or volatilization) may occur as a result of applications of spirodiclofen . The potential for spray drift will be quantitatively evaluated for each pesticide during the Registration Review process that ensures that all uses for that pesticide will be considered concurrently. The approach is outlined in the revised (2012) Standard Operating Procedures for Residential Risk Assessment (SOPs)

– Residential Exposure Assessmen t Standard Operating Procedures Addenda 1: Consideration of Spray Drift. This document outlines the quantification of indirect non

occupational exposure to drift. In terms of volatilization, the agency has developed a Volatilization Screening Tool and a subsequent Volatilization Screening Analysis ( http://www.regulations.gov/#!docketDetail;D=EPA

- HQ

- OPP

- 2014

- 0219 ). During Registration Review, the agency will utilize thi s analysis to determine if data (i.e., flux studies, route

- specific inhalation toxicological studies) or further analyses are required for specific chemicals.

Conclusions : There are no proposed or current registrations for products containing spirodiclof

en that allow residential use. Therefore, residential handler and post

- application exposure assessments will not be needed during Registration Review. The need for spray drift and volatilization risk assessment for spirodiclofen will be examined during Registration Review.

6.0 Aggregate Risk Assessment

The most recent aggregate risk assessment for currently registered uses of spirodiclofen was performed in conjunction with the 20 09 HED human health risk assessment ( Memo, T. Bloem et al.

, 6

- OCT

- 2009; D361071 ). The Agency conducts aggregate exposure assessments by summing dietary (food and water) and residential exposures (residential or other non

occupational exposures). Since there are no registered/proposed uses of spirodiclofen that re sult in residential exposure, the chronic and cancer aggregate risk assessments are equal to the chronic and cancer dietary estimates (food and water only), respectively. Short

- , intermediate

- , and long

- term aggregate

- risk assessments were not performed b ecause there are no registered or proposed uses of spirodiclofen that result in residential exposures.

Conclusions: A new aggregate risk assessment may be required to reflect potential ly revised EDWCs

.Spirodiclofen Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________ _________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ ______ _____________________________________________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ ______ _____________________________________________________________________________________________________________________________ ____________________________________________________________________

Page 9 of 23 

### 7 .0 Occupational Exposure

Spirodiclofen is registered for use on a variety of crops such as citrus, fruit trees, grapes, hops, pome fruits, stone fruits, tree nuts, and Christmas tree plantings . Attachment 4 provides a summary of the occupational use pattern. One end

- use product, a SC formulation , is registered that allows for application rates ranging from 0. 28

- 0. 53 lb ai/A depending on the crop and applications can be made using aerial (for only certain crops) and airblast equipment.

Based on the registered use patterns, there is a potential for dermal and inhalation exposure to spirodiclofen in occupa tional scenarios from handling spirodiclofen products during the application process (i.e., mixer/loaders, applicators, and mixer/loader/applicators). In addition, there is a potential for post

- application worker exposure from entering into areas previously treated with spirodiclofen

. HED notes that b ased on the updated classification of the 28

- day dermal study ( Memo, M. Perron; 07

- OCT

- 2014; D423215)

, a quantitative dermal assessment will no lon ger be required for spirodiclofen.

Occupational Handlers : In the 2009 risk assessment for spirodiclofen, an occupational handler assessment was conducted for aerial and airblast applications at a n application rate of 0. 31 lb ai/A

. T here were no non

- cancer risk estimates of concern (i.e., all combined MOEs ≥ 300 ) provided the PPE recommended on the label (i.e., gloves) was worn

. Cancer risk estimates were at or below 5.6 x 10

- 5 

### for commercial applicators

, and at or below 1.9 x 10

- 5 

### for private fa rmers at baseline or with required personal

- protection equipment ( PPE ) (gloves).

T he 2009 risk assessment d o es not reflect the most up

- to

- date exposure data or inputs for occupational handlers, no r do they reflect the maximum application rate s registered for this chemical. Although a quantitative dermal assessment is no longer required for spirodiclofen, d uring Registration Review, updated occupational handler inhalation assessments may be conducted to reflect the maximum application rates reg istered for spirodiclofen using current ORE policies and updated toxicological inhalation PODs.

Occupational Post Application : A dislodgeable foliar residue ( DFR ) study is available for spirodiclofen. The study was submitted by Bayer Corporation, and ex amined the dissipation of residues on citrus and apple trees following application of spirodiclofen (ENVIDOR ® 

### 2SC Miticide). The study was reviewed by HED, and deemed acceptable for use in occupational post

- application risk assessments (Memo, M. Dow, 29

- J UN

- 2004, D285247, MRID 456973

- 13). These data have been used in previous assessments to assess some (but not all) of the registered crops for spirodiclofen.

In the 2009 risk assessment for spirodiclofen, an occupational post

- application assessment was conducted at an application rate of 0.31 lb ai/A, and represents activities with transfer coefficient s as high as 3, 0 00 cm 2 

### /hr (for thinning fruit). S hort

- term risk estimates were not of concern (i.e., MOEs ≥300) on the day of treatment (i.e., Day 0) for all post

- application exposure activities. In addition, the estimated post

- application cancer risk estimates are below or equal to 1 x 10

- 6



### .

T he most recent occupational post

- application exposure assessment is not reflective of current

e xposure policies and data , nor does it cover t he highest application rate for some crops and the high est post

- application activities

. However, since a quantitative dermal assessment is no longer required for spirodiclofen, an updated occupational dermal post

- application assessment is not required during Registration Review.Spirodiclofen Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________ _________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ ______ _____________________________________________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ ______ _____________________________________________________________________________________________________________________________ ____________________________________________________________________

Page 10 of 23 

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

- application inhalation exposure assessment was not performed for spirodiclofen at this time. If new policies or procedures ar e put into place, the Agency may revisit the need for a quantitative occupational post

- application inhalation exposure assessment for spirodiclofen

.

Conclusions : The occupational exposure database is adequate to support the Registration Review process for spirodiclofen . The most recent occupational handler and post

- application exposure assessments are not reflective of current exposure policies and data, but did not identify risks of concer n. D uring Registration Review, updated occupational handler inhalation
assessments may be conducted to reflect all currently registered uses and maximum application
rates , current ORE policies and/or updated toxicological i nhalation PODs.

8.0 Public Health and Pesticide Epidemiology Data

The Agency has reviewed the available incident data for spirodiclofen (Memo, S. Recore and E. Evans, D422435

, 23

- OCT

- 2014 ) and concludes that based on the low frequency and low severity of cases involving spirodiclof en reported in both the Incident Data System (IDS) and Sentinel Event Notification System for Occupational Risk (SENSOR)

- Pesticides , 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.

9 .0 Tolerance Assessment and International Harmonization

U.S. tolerances and Canadian, Mexican, an d Codex maximum residue limits (MRLs) are summarized in Attachment 5. The U.S., Canadian, and Codex residue definitions are identical except for the Codex definition for livestock

, which does not include the BAJ 2510 metabolite. U.S. tolerance values are harmonized with the Canadian and/or Codex MRLs in many instances but not all. Decisions concerning harmonization of the U.S. tolerance values with either the Canadian and/or Codex MRLs will be made as part of Registration Review

.

10 .0 Environmental J ustice

Potential areas of environmental justice concerns, to the extent possible, were considered in the
most recent spirodiclofen human

- health risk assessment, in accordance with U.S. Executive Order 12898, “Federal Actions to Address Environmental Justi ce in Minority Populations and Low

- Income Populations c



### . ” The 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 drinking water from sources near agricultural areas, the variabilit y 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

ens ure that the risk estimates are based on the best available information.

11.0 Cumulative

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 toxici ty finding for

c http://www.epa.gov/compliance/environmentaljustice/resources/policy/exec_order_12898.pdfSpirodiclofen Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________ _________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ ______ _____________________________________________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ ______ _____________________________________________________________________________________________________________________________ ____________________________________________________________________

Page 11 of 23 

### spirodiclofen and any other substances; and spirodiclofen does not appear to produce a toxic metabolite produced by other substances. For the purposes of this tolerance action, therefore, EPA has assumed that spirodiclofen does not have 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 statemen ts released by EPA’s Office of Pesticide Programs concerning common mechanism determinations and procedures for cumulating effects from substances found to have a common mechanism on EPA’s website at http://www.epa.gov/pesticides/cumulative/.

1 2

. 0 Human Studies

Past spirodiclofen 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. Many such studies, involving exposure to many differe nt pesticides, comprise generic pesticide exposure databases such as the Pesticide Handlers Exposure Database (PHED), the Agricultural Handler Exposure Task Force (AHETF) Database, and the Agricultural Reentry Task Force (ARTF) Database. EPA has reviewed all the studies supporting these multi

- pesticide generic exposure databases, and has found no clear and convincing evidence that the conduct of any of them was either fundamentally unethical or significantly deficient relative to the ethical standards prev ailing at the time the research was conducted. All applicable requirements of EPA’s Rule for the Protection of Human Subjects of Research (40 CFR Part 26) have been satisfied, and there is no regulatory barrier to continued reliance on these studies.

1 3

. 0 Risk Assessment Updates and Data Deficiencies

No data deficiencies were identified for spirodiclofen. EPA notes the following risk assessment updates will need to be completed during Registration Review:

o Toxicology:

o The inhalation endpoint used for spirodiclofen risk assessment will be updated to reflect current HED policy.

o Residue Chemistry/Dietary Exposure:

o The almond hull tolerance should be adjusted from 20.0 ppm to 20 ppm and the meat byproduct tolerances (cattle goat, horse, and sheep) should be adjusted from 0.1 ppm to 0.10 ppm.

o A revised dietary

- exposure analysis may be required to reflect the most recent dietary

- exposure models and potential revised EDWCs (specifically, use of PRZM

- GW)

o Occupational/Residential Exposure:

o Updated occupatio nal handler inhalation assessments may be conducted to reflect all currently registered uses and maximum application rates, current ORE policies and/or updated inhalation toxicological PODs.

o The need for spray drift and volatilization risk assessments for spirodiclofen will be examined during Registration Review.Spirodiclofen Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________ _________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ ______ _____________________________________________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ ______ _____________________________________________________________________________________________________________________________ ____________________________________________________________________

Page 12 of 23 

### 1 4 .0 References

Memoranda Relevant to Registration Review. Author Barcode Date Title Mary Clock

- Rust et al. D285047 June 22, 2005 Spirodiclofen. Human Health Risk Assessment for Use on Citrus Fruit, Grape, Pome Fruit, Stone Fruit, and Tree Nut Crops. Mary Clock

- Rust et al. D339672 April 1, 2008 Human

- Health Risk Assessment for Spirodiclofen for Use on Hops.

Thomas Bloem et al. D361071 October 6, 2009 Spirodiclofen. Human

- Health Risk Assessment Associated with the Section 3 Registration for Application to Avocado, Black Sapote, Canistel, Mamey Sapote, Mango, Papaya, Sapodilla, and Star Apple. Thomas Bloem et al. D371469 July 28, 2010 Spirodiclofen. Human

- Health Risk Assessment Associated with the Section 3 Registration for Application to the Bushberry Subgroup 13

- 07B. Jennifer

- R Tyler et al. D386201 November 11, 2011 Spirodiclofen. Human

- Health Risk Assessment for Proposed Uses

in/on Sugar Apple, Cherimoya, Atemoya, Custard Apple, Ilama, Soursop, Biriba, Lychee, Longan, Spanish Lime, Rambutan, Pulasan, Guava, Feijoa, Jaboticaba, Wax Jambu, Starfruit, Passionfruit, Persimmon, and Acerola. Thomas Bloem D406962 November 20, 2012 Spirodiclofen in/on Citrus Fruit, Grape, Pome Fruit, Stone Fruit,

and Tree Nut Crops. Amended Human

- Health Risk Assessment. Mark I. Dow D285247 June 29, 2004 Review of "Determination of Dislodgeable Foliar Residue in Citrus and Apple Treated with Envidor 2SC Miticide. Mark I. Dow D307979 September 16, 2004 SPIRODICLOFEN

- Exposure/Risk Assessment for the Proposed

Use of Spirodiclofen on Citrus, Grape, Pome Fruit, Stone Fruit and Tree Nuts. Mark I. Dow D315793 April 20, 2005 AMENDMENT TO: SPIRODICLOFEN

- Exposure/Risk Assessment for the Proposed Use of Spirodiclofen on Citrus, Grape, Pome Fruit, Stone Fruit, and Tree Nuts (DP Code 307979, Dated 16 September 2004). Mark I. Dow D337174 April 2, 2007 SPIRODICLOFEN

- Review of "Occupational Exposure & Risk As sessment for Mixer/Loader

- Applicators and Reentry Workers During Use of ENVIDOR on Christmas Trees." Mark I. Dow D346747 December 12, 2007 SPIRODICLOFEN

- Occupational Exposure/Risk Assessment for

the Use of Spirodiclofen on Hops. Mark I. Dow D358809 January 7, 2009 SPIRODICLOFEN

- Exposure/Risk Assessment for the Uses of Spirodiclofen on Grapes and Christmas Trees. Lata Venkateshwara D363346 September 23, 2009 Spirodiclofen: Occupational and Residential Exposure/Risk

Assessment for the Tropical Fruit Subgroup Lata Venkateshwara D371645 August 5, 2010 Spirodiclofen: Occupational and Residential Exposure/Risk Assessment for the Bushberry Subgroup Lata Venkateshwara D387337 November 10, 2011 Spirodiclofen: Occupational and Residential Exposure/Risk

Assessment for Sugar Apple, Cherimoya, Atemoya, Custard Apple, Ilama, Soursop, Biriba, Lychee, Longan, Spanish Lime, Rambutan, Pulasan, Guava, Feijoa, Jaboticaba, Wax Jambu, Starfruit, Passionfruit, Persimmon, and Acerola

T. Bloem D285249 18

- Apr

- 2005 Spirodiclofen in/on Citrus Fruit, Grape, Pome Fruit, Stone Fruit, and Tree Nut Crops. Summary of Analytical Chemistry and Residue Data.

T. Bloem D324834 2

- Feb

- 2006 Spirodiclofen in/on Citrus Fruit, Grape, Pome Fruit, Stone Fruit, and Tree Nut Crops. Review of Amendment Dated 6

- December

- 2005 Submitted in Response to Residue Chemistry Deficiencies Identified in D285249 (T. Bloem, 18

- Apr

- 2005).

T. Bloem D341847 25

- Oct

- 2007 Spirodiclofen in/on Citrus Fruit, Grape, Pome Fruit, Stone Fruit, and Tree Nut Crops. Review of Amendment Dated 6

- December

- 2005 Submitted in Response to Residue Chemistry Deficiencies Identified in D324834 (T. Bloem, 2

- Feb

- 2006).
M. Sahafeyen D346760 9

- Jan

- 2008 Spirodiclofen. Petit ion for Registration for Use on Hops. Summary of Analytical Chemistry and Residue Data.Spirodiclofen Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________ _________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ ______ _____________________________________________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ ______ _____________________________________________________________________________________________________________________________ ____________________________________________________________________

Page 13 of 23 Memoranda Relevant to Registration Review. Author Barcode Date Title

T. Bloem D359773 24

- Jun

- 2009 Spirodiclofen in/on Citrus Fruit, Grape, Pome Fruit, Stone Fruit, and Tree Nut Crops. Review of Amendment Dated 12

- November

- 2008 Submitte d in Response to Residue Chemistry Deficiencies Identified in D341847 (T. Bloem, 25

- Oct

- 2007).

T. Bloem D363343 23

- Sep

- 2009 Spirodiclofen in/on Avocado, Black Sapote, Canistel, Mamey Sapote, Mango, Papaya, Sapodilla, and Star Apple. Summary of Analytical Chemistry and Residue Data.
T. Bloem D368434 23

- Sep

- 2009 Enforcement Methods Forwarded to FDA.

T. Bloem D371643 28

- Jul

- 2010 Spirodiclofen in/on the Bushberry Subgroup 13

- 07B. Summary of Analytical Chemistry and Residue Data.

T. Bloem D390192 20

- Jun

- 2011 Spirodiclofen in/on Citrus Fruit, Grape, Pome Fruit, Stone Fruit, and Tree Nut Crops. Review of Amendment Dated 5

- May

- 2011 Submitted in Response to Residue Chemistry Deficiencies Identified in D359773 (T. Bloem, 24

- Jun

2009).

T. Bloem D387339 10

- Oct

- 2011 Spirodiclofen in/on Sugar Apple, Cherimoya, Atemoya, Custard Apple, Ilama, Soursop, Biriba, Lychee, Longan, Spanish Lime, Rambutan, Pulasan, Guava, Feijoa, Jaboticaba, Wax Jambu, Starfruit, Passionfruit, Persimmon, and Acerola. Summary of Analytical Chemi stry and Residue Data.

T. Bloem D387338 15

- Oct

- 2011 Spirodiclofen. Dietary Risk Assessment in Support of the Requested use on Sugar Apple, Cherimoya, Atemoya, Custard Apple, Ilama, Soursop, Biriba, Lychee, Longan, Spanish Lime, Rambutan, Pulasan, Guava, F eijoa, Jaboticaba, Wax Jambu, Starfruit, Passionfruit, Persimmon, and Acerola.

T. Bloem D396737 15

- Dec

- 2011 Spirodiclofen. Bushberry Subgroup 13

- 07B; changes to the HED

- Recommended Tolerance.

T. Bloem D400006 5

- Jun

- 2012 Spirodiclofen in/on Citrus Fruit, Grape, Pome Fruit, Stone Fruit, and Tree Nut Crops. Review of Amendment Dated 17

- January

- 2012 Submitted in Response to Residue Chemistry Deficiencies Identified in D390192 (T. Bloem, 20

- Jun

2011).

T. Bloem D411178 22

- May

- 2013 Spirodiclofen in/on Citrus Fruit, Grape, Pome Fruit, Stone Fruit, and Tree Nut Crops. Review of Amendment Dated 14

- January

- 2013 Submitted in Response to Residue Chemistry Deficiencies Identified in D40006 (T. Bloem, 5

- Jun

- 2012).



### Attachments: Attachment 1: Chemical Identity Table s . Attachment 2: Spirodiclofen Acute, Subchronic, and Chronic Toxicity Profile

. Attachment 3: Summary of Toxicological Doses and Endpoints for Spirodiclofen

. Attachment 4: Summary of Residues of Concern for Spirodiclofen. Attachment 5: Summary of Registered Uses for Spirodiclofen

. Attachment 6: Spirodiclofen International Residue Limit Status Sheet.

cc: K. Lowe (RAB1) RDI: RAB1 ( 11 / 19 /1 4 ) K. Lowe :S109 48 :PY

- S:(703) 347

- 8989 :7509P:RAB1Spirodiclofen Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________ _________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ ______ _____________________________________________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ ______ _____________________________________________________________________________________________________________________________ ____________________________________________________________________

Page 14 of 23 

### Attachment 1: Chemical Identity Table s .

Table A .1. 1. Spirodiclofen Nomenclature.

Spirodiclofen

Common name Spirodiclofen Company experimental name BAJ 2740
IUPAC name 3

- (2,4

- dichlorophenyl)

- 2

- oxo

- 1

- oxaspiro[4.5]dec

- 3

- en

- 4

- yl 2,2

- dimethylbutyrate
CAS name 3

- (2,4

- dichlorophenyl)

- 2

- oxo

- 1

- oxaspiro[4.5]dec

- 3

- en

- 4

- yl 2,2

- dimethylbutanoate CAS registry number 148477

- 71

- 8
End

- use product (EP) 2 lb/gal FlC (ENVIDOR ® 2SC Miticide; EPA Reg. No. 264

- 831)

Table A .1. 2. Physicochemical Properties of Spirodiclofen

. Melting point 94.8oC

D315459, S. Mathur, 20

- Apr

- 2005 pH 4.2 Density (20oC) 1.29 g/cm 3 Water solubility (20oC at pH 4) 50μg/L

Solvent solubility (g/L at 20°C) n

- heptane xylene dichloromethane 2

- propanol 1

- octanol polyethylene glycol
acetone ethyl acetate acetonitrile dimethylsulfoxide 20

>250 >250 47 44 24 >250 >250 >250 75 Vapor pressure (20oC) 3 x 10

- 7 Pa (2.25 x 10

- 9 mm Hg)
Dissociation constant, pK a Not determinable due to the instability in aqueous solutions at >pH 4 Log(K OW ) at pH 4 and 20oC 5.83
UV/visible absorption spectrum λmax = 201 nm: Not expected to absorb UV at λ >350 nmSpirodiclofen Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________ _________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ ______ _____________________________________________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ ______ _____________________________________________________________________________________________________________________________ ____________________________________________________________________

Page 15 of 23 

### Attachment 2: Spirodiclofen Acute, Subchronic, and Chronic Toxicity Profile

.

Table A. 2 .1. Acute Toxicity for Spirodiclofen.

OPPTS Guideline Study Type Results Toxicity Category

870.1100 Acute oral toxicity / rat LD 50 => 2000 mg/kg (males and females) III

870.1200 Acute dermal toxicity / rat LD 50 => 2000 mg/kg (males and females) III

870.1300 Acute inhalation toxicity / rat LC 50 => 5.03 mg/L (males and females) IV

870.2400 Primary eye irritation / rabbit Non

- irritating IV

870.2500 Primary dermal irritation / rabbit Non

- irritating IV

870.2600 Dermal sensitization / guinea pig Sensitizer

–

Table A. 2 .2. Subchronic, Chronic, and Other Toxicity for Spirodiclofen. Guideline No./ Study Type MRID Nos. (year) Doses/Classification Results

870.3100 Subchronic Oral

- Rat 45696715, 45696716 (1998,2003)

(0,100,500,2500,12500 ppm) M: 0,6. 6,32.1, 166.9, 851.4 mg/kg/day F: 0, 8.1, 47.1, 215.3, 995.8 mg/kg/day Acceptable/guideline For males, NOAEL = 32.1 mg/kg/day, LOAEL = 166.9 mg/kg/day based on increased incidence and severity of small cytoplasmic vacuolation in the cortex of adrenal glands, decreased cholesterol (week 5 and 13), and de creased triglycerides (week 5). For females, NOAEL = 8.1 mg/kg/day, LOAEL = 47.1 mg/kg/day based on increased incidence of small cytoplasmic vacuolation in the cortex of adrenal glands.

870.3100 Subchronic Oral

- Mouse 45696711,45696712,45696713(1997)

(0,100,1000,10,000 ppm) M: 0, 15, 164, 1640 mg/kg/day F: 0, 30, 234, 2685 mg/kg/day Acceptable/guideline For males, NOAEL = 15 mg/kg/day, LOAEL = 164 mg/kg/day based on an increased incidence of hypertrophic Leydig cells in the testes. For females, NO AEL = 30 mg/kg/day, LOAEL = 234 mg/kg/day based on an increased incidence of cytoplasmic vacuolation of the adrenal cortex.

870.3150 Subchronic Oral

- Dog 45696803,45696804 (2000)

(0,200,630,2000 ppm) 0, 7.7 ,26.6 ,84.7 mg/kg/day (M) 0, 8.4 ,28.0, 81.0 mg/kg/day(F) Acceptable/guideline For males, NOAEL = 7.7 mg/kg/day, LOAEL = 26.6 mg/kg/day based on decreased body

- weight gains, increased liver and adrenal weights, decreased prostate weights, and histopathology findings in the adrenal glands, testes, epi didymis, thymus, and prostates. For females, NOAEL  8.4 mg/kg/day. LOAEL =8.4 mg/kg/day based on increased adrenal gland weight (two out of four animals) which coincided with histopathology findings (cytoplasmic vacuoles in the Zona fasciculata of the adr enal glands).
870.3200 28

- Day Dermal Toxicity

- Rat 45696806 (1999)

0, 1000 mg/kg/day Acceptable/Non

- guideline NOAEL = 1000 mg/kg/day (HDT)

. LOAEL = not established

.

870.3700a Prenatal Developmental

- Rat 45696906 (2000)

0, 100, 300,1000 mg/kg/day Acceptable/Guideline Maternal: NOAEL =1000 mg/kg/day (HDT)

. LOAEL = not established

. Developmental: NOAEL = 300 mg/kg/day

. LOAEL = 1000 mg/kg/day based on an increased incidence of slight dilatation of the renal pelvis.Spirodiclofen Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________ _________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ ______ _____________________________________________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ ______ _____________________________________________________________________________________________________________________________ ____________________________________________________________________

Page 16 of 23 Table A. 2 .2. Subchronic, Chronic, and Other Toxicity for Spirodiclofen. Guideline No./ Study Type MRID Nos. (year) Doses/Classification Results

870.3700b Prenatal Developmental

- Rabbit 45696714 (1998)

0, 100, 300, 1000 mg/kg/day Acceptable/guideline Maternal: NOAEL = 100 mg/kg/day

. LOAEL = 300 mg/kg/day based on body

- weight loss and decreased food consumption. Developmental: NOAEL = 1000 mg/kg/day ( HDT)

. LOAEL = not established

.

870.3800 Reproduction and Fertility Effects

- Rat 45696802,45696709 (2000)

(0,70,350,1750 ppm) M: 0, 5.2, 26.2 ,134.8 mg/kg/day F: 0, 5.5, 27.6 ,139.2 mg/kg/day Acceptable/guideline Parental/system: For males: NOAEL = 5.2

- 6.4 mg/kg/day, LOAEL = 26.2

- 30.2 mg/kg/day based on decreased body weight in F 0 males; decreased absolute and relative liver weight in F 0 males; decreased cholesterol and triglycerides in F 1 males; and increased severity of adrenal cortical vacuolation in F 1 males. For females: NOAEL = 5.5

- 7.0 mg/kg/day, LOAEL = 27.6

- 34.4 mg/kg/day based on decreased unesterified fatty acids in F 1 females, and increased severity of adrenal cortical vacuolation in F 0 and F 1 females.

Reproductive : For males: NOAEL = 26.2

- 30.2 mg/kg/day, LOAEL = 134.8

- 177.6 mg/kg/day based on delayed sexual maturation; decreased testicular spermatid and epididymal sperm counts (oligospermia); and atrophy of the testes, epididymides, prostate and seminal vesicles. For females: NOAEL = 27.6

- 34.4 mg/kg/day, LOAEL = 139.2

- 192.7 mg/kg/day based on increased severity of ovarian luteal cell vacuolation/degeneration.

Offspring : NOAEL = 5.2

- 6.4 (M)/5.5

- 7.0 (F) mg/kg/day, LOAEL = 26.2

- 30.2 (M)/ 27.6

- 34.4(F) mg/kg/day based on decreased body we ight and body

- weight gain in F 1 male and female pups.

870.4100b Chronic Toxicity

- dog 45696810,45696811 (2001)

(0,20,50,150,500/600 ppm) M: 0, 0.56 ,1.38 ,4.33 ,16.1 mg/kg/day F: 0, 0.59, 1.52 ,4.74, 17.7 mg/kg/day Acceptable/guideline NOAEL = 1.38 (M)/1.52(F) mg/kg/day, LOAEL = 4.33(M)/4.74 (F) mg/kg/day based on increased relative adrenal weights in both sexes, increased relative testis weight in males and histopathology findings in the adrenal gland of both sexes.

870.4200b Carcinogenicity

- mouse 45696724 (2000)

(0,25,3500,7000 ppm) M: 0, 4.1, 610, 1216 mg/kg/day F: 0, 5.1, 722, 1495 mg/kg/day Acceptable/guideline NOAEL = 4.1(M)/5.1(F) mg/kg/day, LOAEL = 610 (M) mg/kg/day based on increased absolute and relative liver and adrenal weights, decreased absolute and relative kidney weight, enlarged adrenal gland, discolored testis, adrenal gland vacuolization, interstiti al cell degeneration of the testes. For females, LOAEL = 722 mg/kg/day based on increased absolute and relative adrenal weight, decreased absolute and relative kidney weight, increased incidences of adrenal gland pigmentation, and adrenal vacuolization.  Hepatocellular adenoma and carcinoma. 870.4300 Combined Chronic/ Carcinogenicity

- Rat 45696808,45696809 (2000)

(0,50,100,350,2500 ppm) M: 0, 2.0, 4.1, 14.7, 110.1 mg/kg/day F: 0, 2.9, 5.9, 19.9, 152.9 mg/kg/day For males: NOAEL = 14.7 mg/kg/day, LOAEL = 110.1 mg/kg/day based on decreased body weights, decreased body

- weight gain, increased APh levels, decreased cholesterol and triglyceride levels, increased vacuolatedSpirodiclofen Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________ _________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ ______ _____________________________________________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ ______ _____________________________________________________________________________________________________________________________ ____________________________________________________________________

Page 17 of 23 Table A. 2 .2. Subchronic, Chronic, and Other Toxicity for Spirodiclofen. Guideline No./ Study Type MRID Nos. (year) Doses/Classification Results
Acceptable/guideline jejunum enterocytes, and increased incidences of Leydig cell hyperplasia. For females: NOAEL = 19.9 mg/kg/day, LOAEL = 152.9 mg/kg/day based on decreased body weights, decreased body

- weight gain, increased APh levels, increased TSH, uterus nodules, and increased vacuolated jejunum enterocytes.
 tes tes Leydig cell adenoma in males,  uterine adenoma and/or adenocarcinoma in females. 870.5100 Gene Mutation Salmonella typhimurium 45696702

Acceptable/guideline There was no evidence of increased revertant colonies above control in 5 Salmonella strains (TA1535, TA1537, TA1538, TA100, TA98) ± S9 at concentrations up to 5000 μg/plate.

870.5300 In vitro Mammalian Cell Gene Mutation 45696614

Acceptable/guideline Negative, tested in Chinese Hamster lung fibroblast V79 cells at concentrations up to 300 ug/mL

- S9 and +S9. Cytotoxicity was observed at  15 ug/mL

- S9 and 80 ug/mL +S9.

870.5375 In vitro Mammalian Chromosome Aberration 45696615 (1996)

Acceptable/guideline Negative, tested in Chinese hamster lung (V79) cells at concentrations 5

- 80 ug/mL or 0.75

- 12 ug/mL

- S9 or 10

- 160 ug/mL +S9.

870.5395 In vivo Mouse Bone Morrow Micronucleus 45696701 (1996)

Acceptable/guideline Negative, tested at a dose 800 mg/kg (MTD). Clinical signs and cytotoxicity were seen at 800 mg/kg.

870.6200 Acute Neurotoxicity

- Rat 45696725 (2000)

0, 200, 500 ,2000 mg/kg Acceptable/guideline NOAEL = 2000 mg/kg/day, no neurotoxicity observed.

870.6200 Subchronic Neurotoxicity

- Rat 45696726 (2001)

(0,100,1000,12500 ppm) M: 0, 7.2, 70.3, 1088.8 mg/kg/day F: 0, 9.1, 87.3, 1306.5 mg/kg/day Acceptable/guideline NOAEL = 70.3(M)/87.3(F) mg/kg/day. LOAEL = 1088.8(M)/ 1306.5(F) mg/kg/day based on decreased body weights, food consumption, and increased urine staining in both sexes and decreased motor and locomotor activity (week 4) in females only.

870.6300 Developmental Neurotoxicity 46324901 (2004)

(0, 70, 350, or 1500 ppm) 0/0, 6.5/14.0, 32.1/69.7, or 135.9/273.8 mg/kg/day (gestation/lactation) The study classification is reserved for the guideline requirement pending receipt of additional morphometric measurements for the low

- and mid

- dose groups. Maternal NOAEL = 135.9/273.8 mg/kg/day. L OAEL = Not established. Offspring NOAEL = Not established. LOAEL = 6.5/14.0 mg/kg/day based on effects in memory phase of the water maze test in PND 60 females.

870.6300 Developmental Neurotoxicity 47166501 (2007)

(0, 70, 350, or 1500 ppm) 0/0, 5.4/13.0, 28.6/65.7, and 119.2/262.1 mg/kg/day (gestation/lactation) Maternal NOAEL = 119.2/262.1 mg/kg/day. LOAEL= Not established. Offspring NOAEL = 119.2/262.1 mg/kg/day. LOAEL = Not established.

870.7485 Metabolism and pharmacokinetics 45696509 (2000)

Acceptabl e/Non

- guideline Dosed radioactivity was readily absorbed and excreted, with 53.1

- 58.2% of the dose being recovered in the urine by 24 hours post

- dose. Concentrations of radioactivity were highest in the small intestines at 1

- hour post

- dose, followed by li ver and renal cortex. Concentrations in all other tissues (except fat and dental root) were below the concentration in blood. By 4 hours post

- dos e, theSpirodiclofen Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________ _________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ ______ _____________________________________________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ ______ _____________________________________________________________________________________________________________________________ ____________________________________________________________________

Page 18 of 23 Table A. 2 .2. Subchronic, Chronic, and Other Toxicity for Spirodiclofen. Guideline No./ Study Type MRID Nos. (year) Doses/Classification Results

concentrations declined in the small intestines but increased in all other tissues. Radioactivity in the small intestines continued to decline at 8 hours post

- dose, while radioactivity peaked in the bladder and liver (5.460

- 6.463 μg equiv./g). Radioactivity also continued to remain high in fat, renal cortex, and dental root. Concentrations in most tissu es had declined by 6

- to 10

- fold by 24 hours post

- dose. By the 48

- hour interval, concentrations were <LOD in all tissues except liver and renal cortex.

870.7485 Metabolism and pharmacokinetics 45696511 (2000)

2 or 100 mg/kg single dose or 14

- day repeated dose of 2 mg/kg Acceptable/Guideline Absorption was rapid with Tmax values of 3

- 4 hours at low dose and 8 hours for the high dose. Urine and feces were both major routes of elimination. Tissue burdens were negligible. Approximately 11% of the a dministered dose appeared in the bile as biotransformation products. Female rats tended to exhibit greater absorption and urinary excretion than males. Metabolism was extensive with parent compound only detected in small qunatitities in feces.

870.7485 Metabolism and pharmacokinetics 45696512 (2000)

15

- week dietary pretreatment of 50 or 2500 ppm followed by single dose of 2 mg/kg Acceptable/Non

- guideline Urine was a major route of excretion (56

- 75% of administered dose after 48 hours). Elimination via t he feces accounted for 22

- 31% over the same period

. No indication of bioaccumulation. Parent was extensively metabolized with no parent compound detected in the urine. In feces, parent accounted for 0.38

- 13.5% of the administered dose. The dietary pret reatment did not affect metabolism and disposition in the animal.

870.7600 Dermal penetration

- Monkey 45697311 (2002)

6.46 μg/cm 2 Acceptable/Non

- guideline Total absorbed dose (determined as sum of radioactivity in excreta, cage debris, cage wash/wipes, chair wipe, and urine pan wash/wipe) was 2.12±0.94% of administered dose.

870.7600 Dermal penetration

- Monkey 45697312 (2002)

51.6 μCi Acceptable/Non

- guideline Total absorbed dose (determined as sum of radioactivity in excreta, cage debris, cage wash/wip es, chair wipe, and urine pan wash/wipe) was 1.77% of administered dose.

870.7800 Immunotoxicity 49072601 (2013)

(0, 500, 1500, 5500 ppm) 0, 108, 334, 1216 mg/kg/day Acceptable/guideline NOAEL = 1216 mg/kg/day

. LOAEL = not established

.Spirodiclofen Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________ _________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ ______ _____________________________________________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ ______ _____________________________________________________________________________________________________________________________ ____________________________________________________________________

Page 19 of 23 

### Attachment 3: Summary of Toxicological Doses and Endpoints for Spirodiclofen (from 20 09 Risk Assessment)

.

Table A.3.1. Summary of Toxicology Endpoints for Spirodiclofen in Dietary, Non

- Occupational, and Occupational Risk Assessment.
Exposure Scenario Dose Used in Risk

Assessment, UF FQPA SF and Level of Concern for Risk Assessment Study and Toxicological Effects

Acute Dietary An appropriate endpoint attributable to a single dose was not identified. Assessment not necessary.

Chronic Dietary (All populations) NOAEL = 1.38 mg/kg/day

UF = 100 cRfD = 0.014 mg/kg/day FQPA SF = 1X cPAD = cRfD ÷ FQPA SF = 0.014 mg/kg/day Chronic Oral Toxicity Study in Dogs; LOAEL= 4.7 mg/kg/day based on increased relative adrenal weights in both sexes, increased relative testis weight in males and histopathology findings in the adrenal gland of both sexes.

Short

- term Incidental Oral, Dermal and Inhalation (1

- 30 Days) LOAEL = 8.4 mg/kg/day

dermal

- absorption rate= 2% FQPA SF = 3X Residential/Occupational LOC for MOE <300 Subchronic Oral Toxicity Study in Dogs; LOAEL= 8.4 mg/kg/day based on increased adrenal gland weight (two out of four animals) which corroborated with histopathology findings (cytoplasmic vacuoles in the Zona fasciculata of the adrenal glands) in females; a NOAEL for females was not established. Intermediate

- term Incidental Oral, Dermal, and Inhalation (1

- 6 Months) NOAEL = 1.38 mg/kg/day

dermal

- absorption rate = 2% FQPA SF = 1X Residential/Occupational LOC for MOE <100 Chronic Oral Toxicity Study in Dogs; See above under Chronic Dietary.

Long

- term Dermal and Inhalation (>6 Months) NOAEL = 1.38 mg/kg/day

dermal

- absorption rate = 2% FQPA SF = 1X Residential/Occupational LOC for MOE <100 Chronic Oral Toxicity Study in Dogs; See above under Chronic Dietary.
Cancer; Oral, Dermal, and Inhalation Classification: “Likely to be Carcinogenic to Humans”; Q 1 * (mg/kg/day)

- 1 = 1.49 x 10

- 2

. UF = uncertainty factor. RfD = reference dose. LOC = level of concern. MOE = margin of exposure = NOAEL ÷ exposure.Spirodiclofen Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________ _________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ ______ _____________________________________________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ ______ _____________________________________________________________________________________________________________________________ ____________________________________________________________________

Page 20 of 23 

### Attachment 4: Summary of Residues of Concern for Spirodiclofen.

Table A. 4.1: Residues of Concern for Tolerance Expression and Risk Assessment.

Matrix Residues I ncluded in Risk Assessment Residues I ncluded in Tolerance Expression Pome Fruit, Tree Nut, and Hops spirodiclofen spirodiclofen Grape, Citrus Fruit, Stone Fruit, Berry (CG 13), and Tropical Fruit 1 spirodiclofen, BAJ 2510 spirodiclofen Livestock

– Ruminants spirodiclofen, BAJ 2510 spirodiclofen, BAJ 2510 Livestock

– Poultry no data submitted Rotational Crops no data submitted Drinking Water spirodiclofen, BAJ 2510, BAJ 2740

- dihydroxy, BAJ 2740

- ketohydroxy not applicable

1 BAJ 2510 is included as a residue of concern in grape, citrus fruit, stone fruit, berry (CG 13), and tropical fruit due to th e demonstrated (grape and citrus fruit) degradation of parent to BAJ 2510 during processing or due to the lack of data eliminat ing this possibility (stone fruit, berry (CG 13), and tropical fruit). BAJ 2510 is only a residue of concern in the processed commodi ties of grape, citrus fruit, stone fruit, berry (CG 13), and tropical fruit. If processing data for the combined residues of spirodiclofen and BAJ 2510 are not available, then the dietary analysis should incorporate default processing factors.Spirodiclofen Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________ _________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ ______ _____________________________________________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ ______ _____________________________________________________________________________________________________________________________ ____________________________________________________________________

Page 21 of 23 

### Attachment 5 : Summary of Registered Uses for Spirodiclofen

.

Table A.5 .1. Summary of Registered Uses for Spirodiclofen

Use site/Crop Application Equipment Maximum

Application Rate (lb ai/A) Max rate per

crop season (lb ai/A) Max #

apps/crop

season PHI

(days) REI

Citrus Oranges, Grapefruit, Lemons,

Limes, Calamondin, Citrus (citron), Chironja, Tangelos, Tangor , Kumquat, Mandarin, Tangerines, Pummelo, Satsuma

Mandarin Airblast 0.33 0.33 1 7

12 hours Grapes Airblast 0.53 0.53 1 14 Hops Airblas t 0.386 0.386 1 14

Pome Fruits Apples, Crabapples, Loquat,

Mayhaw, Pears, Oriental Pear,

Quince Airblast 0.28 0.28 1 7

Stone Fruits Apricots, Cherries (sweet and

tart), Nectarines, Peach, Plum,

Prunes Airblast 0.28 0.28 1 7

Tree fruits Avocado, Black Sapote,

Canistel, Mamey Sapote, Mangos, Papayas, Sapodilla, Star Apple Aerial (avocado only), Airblast 0.31 0.31 1 2

Tree Nuts Almonds, Beechnut, Brazil Nut, Butternut, Cashews, Chestnuts, Chinquapin, Filberts, Hickory Nuts, Macadamia Nuts, Pecans, Pistachio Nuts, Walnut (black and E nglish) Airblast 0.53 0.53 1 7

Christmas Tree Plantings Aerial and Airblast 0.386 0.386 1 NASpirodiclofen Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________ _________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ ______ _____________________________________________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ ______ _____________________________________________________________________________________________________________________________ ____________________________________________________________________

Page 22 of 23 

### Attachment 6 : Spirodiclofen International Residue Limit Status Sheet.

Table A.6 .1. Summary of US and International Tolerances and Maximum Residue Limits

Residue Definition US Canada Mexico 1 Codex

40 CFR §180.608 Plants: (1) Tolerances are established for residues of spirodiclofen, including its metabolites and degradates, in or on the commodities listed below. Compliance with the following tolerance levels is to be determined by measuring only spirodiclo fen Livestock: (2) Tolerances are established for residues of spirodiclofen, including its metabolites and degradates, in or on the commodities listed below. Compliance with the following tolerance levels is to be determined by measuring only spirodiclof en and its metabolite 3

- (2,4

- dichlorophenyl)

- 4

- hydroxy

- 1

- oxaspiro[4,5] dec

- 3

- en

- 2

- one, calculated as the stoichiometric equivalent of spirodiclofen Plants: spirodiclofen Livestock: spirodiclofen including the metabolite 1

- oxaspiro[4.5]dec

- 3

- en

- 2

- one, 3

- (2,4

- dichlorophen yl)

- 4

- hydroxy

- (9CI) -- spirodiclofen (the residue is fat soluble)

Tolerance/Maximum Residue Limit (ppm)

Commodity 1 US Canada Mexico 1 Codex 2
Almond, hulls 20

-- -- 15 Apple, wet pomace 2.4

-- -- 4 apple pomace, dry

Avocado 1.0 1

-- -- Black sapote 1.0 1

-- -- Canistel 1.0 1

-- -- Citrus, juice 0.60 0.6

-- -- Citrus, oil 35 20

-- --

Fruit, citrus, group 10 0.50 0.5 calamondin , citrus citron, citrus hybrids, grapefruits, kumquats, lemons, limes, oranges, pummelos, Satsuma mandarins, tangerines -- 0.4

Fruit, pome, group 11 0.80 0.8 apples, Asian pears, azaroles, Chinese quinces, crabapples, Japanese quinces, loquats, mayhaws, medlars, pears, quinces -- 0.8

Fruit, stone, group 12 1.0 1 apricots, fresh prune plums, nectarines, peaches, plumcots, plums, sweet cherries, tart cherries -- 2

Grape 2.0 2

-- 0.2
Grape, raisin 6.0 4 raisins

-- 0.3 dried grapes (=currants, raisins, and sultanas) Hop, dried cones 30 40

-- 40 hops, dry Mamey sapote 1.0 1

-- -- Mango 1.0 1

-- --

Nut, tree, group 14 0.10 0.1 almond nuts, beechnuts, black walnuts, Brazil nuts, butternuts, cashew nuts, chestnuts, chinquapin nuts, English walnuts, hazelnuts (filbert), hickory nuts, macadamia nuts, pecan nuts -- 0.05

Papaya 1.0 1

-- 0.03 (*) Pistachio 0.10 0.1

-- 0.05 tree nuts Sapodilla 1.0 1

-- -- Star apple 1.0 1

-- -- Cattle, fat 0.02 0.02

-- --Spirodiclofen Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________ _________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ ______ _____________________________________________________________________________________________________________________________ _____________________________________________________________________________________________________________________________ ______ _____________________________________________________________________________________________________________________________ ____________________________________________________________________

Page 23 of 23 Table A.6 .1. Summary of US and International Tolerances and Maximum Residue Limits
Cattle, meat byproducts 0.10 0.1

-- 0.05 (*) edible offal (mammalian)

Cattle, meat 0.02 0.02

-- 0.01 (*) (fat) meat (from mammals other than marine ammmals) Goat, fat 0.02 0.02

-- -- Goat, meat byproducts 0.10 0.1

-- 0.05 (*) edible offal (mammalian)

Goat, meat 0.02 0.02

-- 0.01 (*) (fat) meat (from mammals other than marine ammmals) Horse, fat 0.02 0.02

-- -- Horse, meat byproducts 0.10 0.1

-- 0.05 (*) edible offal (mammalian)

Horse, meat 0.02 0.02

-- 0.01 (*) (fat) meat (from mammals other than marine ammmals)
Milk 0.01 0.01

-- 0.004 (*) Milk, fat 0.03 0.03

-- -- Sheep, fat 0.02 0.02

-- -- Sheep, meat byproducts 0.10 0.1

-- 0.05 (*) edible offal (mammalian)

Sheep, meat 0.02 0.02

-- 0.01 (*) (fat) meat (from mammals other than marine mammals) MRLs with no U.S. equivalent Coffee beans

-- -- -- 0.03 (*) Cucumber

-- -- -- 0.07 Currants, Black, Red, White

-- -- -- 1 Gherkin

-- -- -- 0.07 Peppers, sweet (including pimento or pimiento) -- -- -- 0.2
Strawberry

-- -- -- 2
Tomato

-- -- -- 0.5 Grape juice

-- 2.4

-- -- Completed: M. Negussie; 08/27/14

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.