### Dimethoate Human H ealth Ri sk A ssess ment DP No

. 0 4 16010



### UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON

, D .C. 20460

OFFICE OF
CHEMICAL SA FETY AND
POLLUTION PREVEN TION



### D A TE: 15

- SEP-2015



### SUBJECT: Dimethoat e : Human Health Risk Assessment for Regi s tration R ev i ew



### PC Co d e : 03500 l


### Deci s i on No.: 484715



### Petition No.: NA 

### DP Barcode: D41 60 1 0 

### Registration No.: NA 

### Regu l atory Act i on: Regi s tration Review



### Case N o .: 0088 

### Risk Assessme nt Type: Sing l e ChemicaVAggre g at e 

### T XR No.: NA 

### CAS No.: 60-51

- 5

MRID 

### No .: NA 40 

### CFR : § l 80

. 204



### FROM: 

## ill/ 

# ¥Y1;
LI U -/ ..f!Ar- 

### Monique M. P e rron
, Sc .D.

, Toxicologist /**""'** 

## · George F. Kramer. Ph.D

., Senior Chemist
Kelly M. Lowe

, SeniorEnvfs·r

## nmen!aj~~nti~**~~~** Jennifer R. Tyler

, C h emis t**~~** 

# -
Risk Assessment Branch 1 · B 1 

# f

. Juli e L. 

### Van Alstine, M PH, E n vironmental H e alth Sc i ent i st

Risk Assessment Branch I 

### ( RA86 )

H ealth E ffects Division ( HED ; 7509 P )



### THROUGH: Thur st on Morton, Acting Branch Chief 

# I;

TO : RABl / HED (7509 P ) / '-'

And

Sheila Piper

, Risk As s essment Review Committee (RARC) R eviewer

# ~JL_ QP"J

J eff Dawson

, RARC**Reviewer ~** 



### K e ll y B allard

Neil Ander so n Risk Mana ge m e nt and Implem e ntation Br anch I

P es ticid e Re-Evaluati o n Divi s ion (PRD) (7 508P )

This docum e nt provide s t he HED ' s hwnan hea l th risk assessment for the Reg i stra ti o n Review of

dimethoate ( 0

, 0

- dimethyl S -[ 2 -(methylamino )-2-oxoethy l] phosphorodithioate). The hazard

c haracteri zat i o n
, endpoint se l ec tion

, and risk a ss es s ment were provided by Monique Perron (RA B l ); the residue ch e mi st r y a ssess m e nt w a s pro v ided by Geo r ge Kram e r (RAB 1 ), dietary

e xposure assessmen t s were provided by Juli e Van Alstine (RA B 6); the occupationa l and

residential expo s ure assessment was provid e d by Kell y L owe and J e nnifer Tyler (RA BI ); and

the drinking water a ssess ment wa s pro vided by Jo se Melend e z of the Environmental Fate and

Eff ec t s Di v i s ion (EFE D )

.

Page I of 104

### Dimethoate Hwnan Health Risk Assessme nt DP No. 0416010



# Table of Contents

1.0 Executive Summary

....................................................... . ... .. .. ... .. .... ....... .. .... ...... .................. 4

2.0 HED R eco mmendation s

....................................................................................................... 8

2

. 1 Data Defici e nci es

............................................................................................................. 8

2

. 2 Tolerance Considera tion s

..................................... . ........................................................... 8

2.2.1 Enforcement Analytical Method

. .. .. ... .. ... ... ....................... .. .. ......... .. . ..... . .................. 8

2.2.2 Internati onal Harmonization

........................................ .. ... . ...... .. .. . ... . ..... .. .... .. . . ..... .. .. 9

2.2.3 R ecommended Tolerances

................................ . ........... . ... .. ..... .. .. .. .. . ..... .. ....... .. ........ 9

2.2.4 R ev i sions to Es tabli s hed Tolerances

.. . .... .. ... .. ........................................................... 9

2.3 Label Recornmendatio n s

. .. ... . ......................................................................................... l 0

2.3. l Rec o mm e ndation s from R es idential Assessment

........ .. .. ......... .. .. .. ..... . ........ .. .... .. . . 10



### 3.0 Introduction

. . .............. .. ... . .................................................................................................. 10

3 .1 Chemical Identity

.. .. ... . .... . .................................................................................. . ........... 10



### 3.2 Ph ys i cal/Chemical Characteristics

........................................................................... . .. . .. 11

3

. 3 Pesticide Use Pattern

...................................................................................................... 1 I



### 3.4 Antic ip ated Exposure Path ways

..................................................................................... 11



### 3.5 Consideration of Enviro nm e nt al Ju s ti ce

.... . ..................... ................................ .... ..... .... . 11

4.0 Hazard Characterization and Dose-Response Assessment..

. ... .. .. .. ......... .. .. . ..... . ... . ............ 12

4.1 Toxicology Studies Available fo r Analysis

... .. ... .. ... .. .......... . ... .. ............. . ...................... 12

4.2 Absorption

, Di st ribution

, Metabolism, & 

### Exc r etion (ADME)

...................................... 13

4.2.1 Dim ethoate

.......................... .. .. ......... .. .. ... .. .... . ........................................ . .. .... .. .. ...... 13

4.2.2 Omethoate

.. ...... .. .. .. .. ... .. .. ... .. ... .. .... . .... . .... .. ... .. .. ... .. ......... ... .. .................................... 14

4.2.3 Dermal Absorption

.................................................................................................. 14

4.3 Toxicological Effects

.. . .............. . ................................................... . .. ... .... .. . .............. .. ... 15

4

. 3. l Critical Dur at i ons of Exposure

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

### 16

4.4 Literature Review on Neurodevelopment Effec t s

.............................................. . ..... . ..... 17

4.5 Safety F actor for lnfant s and Children (F QPA SF)

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

4.5. l Completeness of the Toxicolo gy Database

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

4.5.2 Ev iden ce of Neurotoxicity

...................................... . ... .. ... . .......... . ........................... 23

4.5.3 Evidence of Se n sitivity / Susceptibility in the Developing or Young Animal

....... .. 23

4.5.4 Residu a l Uncertainty in the Exposure Database

. .... . ............................................... 23

4.5 Toxicity Endpoint and P oint of Departure Selections

.................................................... 23

4.5.1 Dose-Response Assessment..

.................................................................................. 23

4.5.2 Toxicity Adjustment Factors for Omethoate

.................... .. ......... .. . ............... .. . ...... 27

4

. 5.3 Recommendation fo r Combining Routes of Exposures for Ri sk Assessment..

..... . 28

4.5.4 Cance r Classification and Risk Assessment R ecomme ndation

... . .......................... 28

4.5.5 Summary of Points of Departure and Toxicity Endpoints Used in Hum an Risk

Assess 1n en t

.... .. ................... . .................................. .. ... .. .. ... .. .. .............. .. ......... . ..... . ... . ..... . ...... 28

4.6 Endocrine Disruption

.. .. .. ................... .. ................... .. .. ... ... .... .. .. .. ...................... .. .... . ...... 30

5.0 Dietary Expos ure and Risk Assessment

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

5 .1 Metabolite/Oegradate R es idue Pro file

........................... .. .............................................. 31

5 .1. l Summary of Plant and Animal Metabolism Studies

........................................ . ...... 31

5

. 1.2 Summary of Environmental Degradation

.......... .. ...................................... . ..... . .. .... 31



### 5.1

. 3 Compa ri son of Metabo li c Pathwa ys

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

### 32

5.1.4 Residues of Concern Summary and Ration ale

... . .. .......... .. .. ... . ............................. . .. 32

5.2 Food R es idue Profile

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

### 32

5.3 Water R esid ue Pr ofi l e

................................................... . ........... .. . ......... ......................... 33

5.4 Dietary Risk Assessment.

........... . ............... .. ... .. ... .. .. ... ................................................... 34

Page 2of104Dimethoate Human Health Risk Assessment DP No. D416010

Page 3 of 104 

### 5.4.1 Overview of Residue Data Used

................................ ................................ ............. 34

5.4.2 Percent Crop Treated Used in Dietary Assessment

................................ ................ 35

5.4.3 Acute Dietary Risk Assessment

................................ ................................ .............. 35

5.4.4 Steady

- State Dietary Risk Assessment

................................ ................................ ... 36

5.4.5 Cancer Dietary Risk Assessment

................................ ................................ ............ 36 5.4.6. Dietary Assessment Summary Tables

................................ ................................ ........ 37

6.0 Residential (Non

- Occupational) Exposure/Risk Characterization

................................ .... 47

6.1 Residential Handler Exposure

................................ ................................ ........................ 47

6.2 Post

- Application Exposure

................................ ................................ ............................. 47

7.0 Non

- Occupational Bystander Post

- Application Inhalation Exposure and Risk Estimates 47

8.0 Non

- Occupational Spray Drift Exposure and Risk Estimates

................................ ........... 47

8.1 Combined Risk Estimates from Lawn Deposition Adjacent to Applicat ions

................ 49

9.0 Aggregate Exposure/Risk Characterization

................................ ................................ ....... 50

10.0 Cumulative Exposure/Risk Characterization

................................ ................................ ..... 51

11.0 Occupational Exposure/Risk Characterization

................................ ................................ .. 51

11.1 Short

- and Intermediate

- Term Handler Risk

................................ .............................. 51

11.2 Short

- /Intermediate

- Term Post

- Application Risk

................................ ...................... 58

11.2.1 Occupational Post

- application Inhalation Exposure/Risk Estimates

...................... 58

11.2.2 Occupational Post

- application Dermal Exposure/Risk Estimates

.......................... 58

12.0 References

................................ ................................ ................................ .......................... 71 Appendix A. Toxicology Profile

................................ ................................ ................................ .. 74

A.1 Toxicology Data Requirements

................................ ................................ ...................... 74 Appendix B. Summary of OPP’s Cholinesterase Policy & Use of BMD Modeling

................... 85 Appendix C. Summary Tables of Benchmark Dose (BMD) Analyses in Rat Toxicity Studies

. 87 Appendix D. Tolerance Summary for Dimethoate

................................ ................................ ...... 89 Appendix E. Physical/Chemical Properties

................................ ................................ ................. 91 Appendix F. Use Summary for Dimethoate

................................ ................................ ................ 92 Appendix G. International Residue Limits

................................ ................................ .................. 99 Appendix H

– Summary of Surface Water EDWCs using Maximum and Typical Application

Rates

................................ ................................ ................................ ................................ ............ 102Dimethoate Human Health Risk Assessment DP No. D416010

Page 4 of 104 

### 1.0 Executive Summary

Background

Dimethoate is a general use systemic, organophosphate (OP) insecticide/acaricide that is used to

control a wide variety of insect pests. There are numerous end

- use product labels registered with

dimethoate as the active ingredient . These include liquid and water

- soluble packets ( WSP )

formulations. The labeled use sites include various agricultural crops, Christmas tree farms

, trees grown for pulp, and ornamentals in outdoor nurseries . Most of the registered products are applied via aerial, chemigation, airblast, groundboom

, or with handheld equipment. For most use sites/crops, the maximum application rate is 2 lb ai/A, but f or ornamentals in outdoor nurseries, the maximum application rate is 4.15 lb ai/A for air blast applications specifically.

There are currently no registered or proposed residential uses of dimethoate

.

Hazard Assessment

Dimethoate is a member of the OP cl ass of pesticides. Like other OPs, the initiating event in the

adverse

- outcome pathway (AOP)/ mode of action (MOA) for dimethoate involves inhibition of the enzyme acetylcholinesterase (AChE) via phosphorylation of the serine residue at the active

site of the enzyme. This inhibition leads to accumulation of acetylcholine and ultimately to neurotoxicity in the central and/or peripheral nervous system . For dimethoate , AChE inhibition is the most sensitive endpoint in the toxicology database in multiple spec ies, durations, lifestages, and routes . Dimethoate, like some other OPs, requires metabolic activation to its oxon

metabolite ( omethoate ) to inhibit AChE, with subsequent metabolism that leads to detoxification. OPs also exhibit a phenomenon known as ste ady

- state AChE inhibition. After repeated dosing at the same dose level, the degree of inhibition comes into equilibrium with the production of new, uninhibited enzyme. Therefore, a steady

- state exposure assessments of 21 days and longer were conducted instead of the traditional chronic or long

- term assessments.

The toxicology database s for dimethoate and omethoate are complete for risk assessment. There are acceptable studies available for toxicity endpoint selection. Dimethoate and omet hoate have high

- quality dose

- response data across multiple lifestages, durations, and routes for both red blood cell (RBC) and brain AChE inhibition. High

- quality dermal and inhalation studies allow

for route

- specific evaluation. Clinical signs of neurot oxicity can be found throughout the

database s at doses much higher than those causing inhibition of AChE. No studies in the toxicology database s suggest quantitative sensitivity to dimethoate /omethoate based on AChE inhibition. Increased pup mortality wa s observed in several studies, but regulation of exposure to
dimethoate and its oxon omethoate using brain AChE inhibition is protective of the observed pup mortality. For all exposure scenarios, interspecies (10X) and intraspecies (10X) uncertainty

facto rs were applied. The Food Quality Protection Act (FQPA) Safety Factor (SF) has been retained for infants, children, youths, and women of childbearing age for all exposure scenarios due to uncertainty in the human dose

- response relationship for neurodevelo pmental effects (see Section 4.4). As a result, the FQPA SF was applied to all exposure scenarios except for dietary exposures for the adult population subgroup 50

- 99 years old, where the FQPA SF did not apply (total uncertainty factor = 100X).Dimethoate Human Health Risk Assessment DP No. D416010

Page 5 of 104 

### Dimethoate is classified as a Group C carcinogen (possible human carcinogen). The Agency determined that quantification of risk using a non

- linear approach would adequately account for all chronic toxicity, including carcinogenicity that could result from exposure to dimethoate.

Toxicity Adjustment Factors

As the oxon metabolite of dimethoate, omethoate has been found to be a more potent AChE inhibitor. To account for the increased potency of omethoate in risk estimates, benchmark dose ( BMD ) modeling wa s used to evaluate relative potency for dimethoate and omethoate and to

estimate the toxicity adjustment factors ( TAFs ) for acute and steady

- state exposure durations.

The acute TAF from the Reregistration Eligibility Document ( RED) for omethoate has been updated to 8X . The steady

- state TAF of 3X for omethoate used in the RED was verified with additional data; therefore

, no changes were made to the steady

- state TAF

.

Dietary (Food and Water) Exposure and Risk

Highly refined a cute and steady

- state dietary exposure and risk assessments for dimethoate and its metabolite omethoate were conducted using the Dietary Exposure Evaluation Model software with the Food Commodity Intake Database (DEEM

- FCID) Version 3.1 8 . Th is model use s 2003

- 2008 food consump tion data from the U.S. Department of Agriculture’s (USDA’s) National

Health and Nutrition Examination Survey, What We Eat in America, (NHANES/WWEIA). The steady

- state dietary assessments provide a conservative estimate of 21

- day average daily

exposures u sing two

- day average dietary exposure and 21

- day rolling water averages . Acute and steady

- state assessments were conducted for food only, drinking water only, and for food and drinking water.

The acute and steady

- state dietary exposure assessment s inco rporated USDA Pesticide Data Program (PDP) data for dimethoate and omethoate, percent crop treated (PCT) data from the Biological and Economic Analysis Division (BEAD), empirical and default processing factors,

and cooking factors derived from literature s tudies . Additionally, acute and steady

- state TAF s of

3X and 8X

, respectively, were applied for omethoate residues. EFED provided daily time

- series outputs that simulate 29 years of residues in drinking water for 44 different application scenarios.

These scenarios encompass both maximum (24 scenarios) and typical (20 scenarios) application rates for agricultural and non

- agricultural uses of dimethoate . The drinking water distributions

assume 100% conversion of dimethoate to omethoate 1 

### and inc orporate the acute and steady

- state

TAF values

. For steady

- state assessments, 21

- day rolling water averages were used to estimate

21

- day average daily food and drinking water exposures.

The acute dietary (food only) exposure estimates exceed HED’s level of concern ( LOC; > 100%

of the acute population adjusted dose (aPAD) ) for the U.S. population and all population subgroups at the 99.9 th 

### percentile. T he U.S. population was 270% of the aPAD and children 1

- 2 years old, the most highly exposed population subgroup , was 640% of the aPAD

. For the acute drinking water only runs, all (24) of the maximum application rate and 19 of the typical application rate drinking water scenarios resulted in risks of concern at the 99.9 th 

### percentile. Since the food alone and drinking w ater alone assessments result in risks of concern, acute food and drinking water analyses were not completed for all of the scenarios since they would also

1 MRID 48041103

- Marin, J.E. 2010. Determination of the effect of chlorination on the degradation of dimethoate

in water.Dimethoate Human Health Risk Assessment DP No. D416010

Page 6 of 104 

### result in risks of concern at the 99.9 th 

### percentile. Overall, acute food and drinking water analyse s were conducted for 27 (7 maximum application rate and 20 typical application rate) drinking

water scenarios. All infants (<1 year old) was the most highly exposed population subgroup for 11 of the scenarios, with food and drinking water risk estimates t hat ranged from 710

- 1100% of

the aPAD at the 99.9 th 

### percentile. Children 1

- 2 years old was the most highly exposed population subgroup for 16 of the scenarios, with food and drinking water risk estimates that ranged from 640

- 680% of the aPAD at the 99.9 th 

### percentile.

The food only steady

- state results exceed HED’s LOC ( > 100% of the steady

- state population

adjusted dose (ssPAD)) for the U.S. population and all population subgroups at the 99.9 th


### percentile. T he U.S. population was 410% of the ssPAD an d children 1

- 2 years old, the most highly exposed population subgroup , was 810% of the ssPAD

. For the steady

- state drinking water only analyses, all (24) of the maximum application rate and 19 of the typical application rate drinking water scenarios resul ted in risks of concern at the 99.9 th 

### percentile. Since the food alone and drinking water alone assessments result in risks of concern, steady

- state food and drinking water analyses were not completed for all of the scenarios since they would also result

in risks of concern at the 99.9 th 

### percentile. Overall, f ood and drinking water steady

- state analyses were conducted for 23 drinking water scenarios (3 maximum application rate and 20 typical application rate). All infants (<1 year old) was the most highl y exposed population subgroup for six of the scenarios, with food and drinking water risk estimates that ranged from

970

- 1200% of the ssPAD at the 99.9 th 

### percentile. Children 1

- 2 years old was the most highly exposed population subgroups for 17 of the sce narios, with food and drinking water risk

estimates that ranged from 810

- 880% of the ssPAD at the 99.9 th 

### percentile.

Residential (Non

- Occupational) Exposure and Risk

All residential and other non

- occupational uses of dimethoate were voluntarily cancelled, effective March 13, 2002 (Federal Register Notice/Vol. 67, No. 84/Wednesday, May 01, 2002/Notices/21669).

Non

- Occupational Spray Drift Exposure and Risk

A quant itative non

- occupational spray drift assessment was conducted for the registered uses of

dimethoate. The assessment takes into consideration both dimethoate residues and residues of the major metabolite, omethoate. Adult dermal and children’s (1 to < 2 y ear old) dermal and incidental oral risk estimates from indirect exposure related to spray drift exceed HED’s level of concern (MOEs < 100 0 ) at a range of distances from the edge of the field depending on the

spray

- drift scenario (e.g., 0 to >300 feet). R esults indicate that the major spray

- drift risk

concern s are from aerial applications.

Volatilization/Residential Bystander

Volatilization of pesticides may be a source of post

- application inhalation exposure to individuals nearby pesticide applications . The agency has developed a Volatilization Screening Tool and a subsequent Vo latilization Screening Analysis, and d uring Registration Review, the Agency will utilize this analysis to determine if data (i.e., flux studies) or further analyse s are required for dimethoate.Dimethoate Human Health Risk Assessment DP No. D416010

Page 7 of 104 

### Aggregate

The registered dimethoate uses are not anticipated to result in residential exposure and thus t he

acute and steady

- state dietary exposure estimates represent the acute and steady

- state aggregate

exposure. Dimethoate is classified as a Group C carcinogen (possible human carcinogen)

. Quantification of risk using a non

- linear approach will adequately account for all chronic toxicity, including carcinogenicity that could result from exposure to dimethoate.

Oc cupational Exposure and Risk

Occupational handler dermal and inhalation exposure and risk estimates were calculated for the registered uses of dimethoate. The occupational handler exposure and risk estimates indicate

that the dermal and inhalation combin ed MOEs are of concern to HED (i.e., MOE s < 100 0 ) for most scenarios assuming the use of label

- required PPE. As was noted above, the inhalation risk estimates are considered to be a conservative estimate of exposure to dimethoate residues considering the inhalation POD was selected from an omethoate toxicity study. Only five scenarios (out of 40) reach an MOE above the LOC of 1000 at some level of PPE (above what is currently required on the labels) or with engineering controls.

O ccupational post

- applica tion dermal exposure and risk estimates were assessed for all registered uses of dimethoate using submitted chemical

- specific dislodgeable foliar residue (DFR) data. The post

- application assessment takes into consideration both dimethoate residues

and res idues of the major metabolite , omethoate ; both of which were measured in the available

DFR studies

. Based on the current exposure assessment, post

- application risk estimates remain a concern in some situations for more than 30 days after application (i.e. , MOEs < 1000). Current product

- label REIs range from 48 hours to 24 days depending on the crop and geographic location (i.e., arid versus non

- arid). Even though REIs of 12 and 24 hours may be long enough for MOEs to reach the LOC of 1000 for some crops/activities, HED recommends a minimum REI of 48 hours (72 hours in arid regions) to be protective of potential for exposure to omethoate which is known to form after application. These REIs are in line with the 40 CFR 156.208 (c) (2 ) assignments for active ingredients that are classified as Toxicity Category I for acute dermal, eye irritation

, and primary skin irritation

.

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

- cancer occupat ional post

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

post

- application inhalation exposure ass essment for dimethoate

.

Human Studies Review :

This risk assessment relies in part on data from studies in which adult human subjects were intentionally exposed to a pesticide or other chemical. These data, which include studies from Pesticide Handler Exposure Database (PHED) 1.1, Outdoor Residential Exposure Task Force (ORETF), the Agricultural Handlers Expos ure Task Force (AHETF) database, and the Agricultural Reentry Task Force (ARTF) database are (1) subject to ethics review pursuant to 40 CFR 26, (2) have received that review, and (3) are compliant with applicable ethics requirements. For certain studies, the ethics review may have included review by the HumanDimethoate Human Health Risk Assessment DP No. D416010

Page 8 of 104 

### Studies Review Board. Descripti ons of data sources, as well as guidance on their use, can be found at the Agency website 2



### .

2.0 HED Recommendations

2.1 Data Deficiencies

There ar e no data deficiencies for the Registration R eview eligibility of dimethoate

.

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

Plants: For the purpose of R egistration R eview, adequate methods are available for the enforcement of plant commodity tolerances. The Pesticide Analytical Manual (PAM) Vol. II

lists three gas

- liquid chr omatography ( GLC ) methods (Methods A, B, and C) using flame photometric detection, and a colorimetric procedure (Method D) for analysis of residues of dimethoate and its oxygen analog in/on plant commodities. A second colorimetric procedure (Method E) is listed for the determination of residues of dimethoate per se . The limit of quantitation (LOQ) for the GLC methods is 0.05 ppm. A thin

- layer chromatography (TLC) method is also listed (Method I) for determination of residues of dimethoate and its oxygen analog in/on plant commodities. The QuEChERS multiresidue method has also been validated for determination of dimethoate and omethoate (https://www.chromspec.com/pdf/e/uct19.pdf).

Livestock: For the purpose of Registration R eview, an adequate method is available for the enforcement of livestock commodity tolerances. The method was modified from the QuEChERS multiresidue method. Briefly, samples are extracted with acetonitrile (ACN) or ACN/water (fat), shaken, and sonicated. The extract is partitioned with magnesium sulfate, sodium chloride, and a citrate buffer (sodium citrate dibasic sesquihydrate and sodium citrate tribasic dehydrate). The citrate buffer is not added for eggs. An aliquot of the organic layer

extract is cleaned

- up using d ispersive s olid

- phase extraction (dSPE) PSA/ENVI

- Carb SPE

Clean

- Up Tubes, filtered, diluted with ACN, and analyzed by liquid chromatography

- mass spectroscopy/mass spectroscopy (LC

- MS/MS) using electrospray ionization (ESI) in the positive

- ion mode. The method monito rs three ion transitions for determination of dimethoate

and omethoate. The validated LOQ (determined as the lowest level of method validation, LLMV) is 0.001 ppm for each analyte in all livestock matrices. The reported limit of detection (LOD) is 0.0005 ppm for each analyte in egg, muscle, liver, kidney, and fat and 0.00025 ppm in

milk.

Multiresidue Methods : The data requirements for multiresidue methods (MRMs) are fulfilled.

The 1/94 Food and Drug Administration ( FDA ) PESTDATA database (PAM Volume I, Appendix I) indicates that residues of dimethoate and omethoate are completely recovered (>80%) by MRM Section 302 (Luke Method; Protocol D) but are not recovered by MRM Sections 303 (Mills, Onley, Gaither Method; Protocol E, nonfatty) and 304 (Mills fatty food method; Protocol E, fatty).

2 http://www.epa.gov/pesticides/science/handler

- exposure

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

- app

- exposure

- data.htmlDimethoate Human Health Risk Assessment DP No. D416010

Page 9 of 104 

### 2.2.2 International Harmonization

U.S. permanent tolerances (listed in 40 CFR § 180. 204 ) plus Mexican, Canadian, and Codex maximum residue levels (MRLs) are summarized in Appendix G. The U.S. and Canadian residue definitions are harmonized (parent plus omethoate); however, the Codex residue definition is parent only. For some raw agricultural commodities, the levels of the tolerances/MRLs for the U.S., Canada, Mexico, and Codex are harmo nized; however, there are many commodities for which the levels are not harmonized. Harmonization of the tolerance/MRL levels for beans, cauliflower, celery, pea, pepper, potato, tomato, turnip tops

, and wheat, straw is not possible, as the U.S. use patte rns require a higher tolerance. Harmonization of the tolerance/MRL levels for livestock meat byproducts, milk, egg, and citrus is not possible as the U.S. tolerances are significantly lower. Harmonization of the tolerance/MRL level for wheat, grain is po ssible as the U.S. tolerance level (0.04 ppm) is only slightly lower that the Codex MRL level (0.05 ppm).

2.2.3 Recommended Tolerances

Permanent tolerances have been established in 40 CFR §180.204 for the total residues of the insecticide dimethoate ( O

, O

- dimethyl S

- ( N

- methylcarbamoylmethyl) phosphorodithioate) including its oxygen analog in/on various raw agricultural commodities ranging from 0.002 ppm to 5.0 ppm.

The tolerance expression for dimethoate [40 CFR §180.204(a)(1) and 40 CFR §180.204(c)] has been reviewed and should be updated as follows based on HED’s Interim Guidance on Tolerance Expressions (S. Knizner, 27

- MAY

- 2009).

Tolerances are established for residues of the insecticide dimethoate, including its metabolites and degradates, in or on th e commodities in the table below. Compliance with the tolerance levels specified below is to be determined by measuring only the sum of dimethoate ( O,O

- dimethyl S

- [2

- (methylamino)

- 2

- oxoethyl] phosphorodithioate) and its oxygen analog ( O,O

- dimethyl S

- [2

- (m ethylamino)

- 2

- oxoethyl] phosphorothioate), calculated as the stoichiometric equivalent of dimethoate, in or on the commodity.

A summary of the established and HED

- recommended tolerances for residues of dimethoate can be

found in Appendix D

.

2.2.4 Revisions to Established Tolerances

HED is recommending for revisions to the tolerance expression in order to conform to current Agency policy. In addition, HED is recommending for the establishment of a tolerance for residues in/on fruit, citrus, group 10

- 10 concomitant with the deletion of the tolerances for residues in/on the individual members of the crop group; revocation of the tolerance for residues in/on sweet corn forage as there is no registered use on sweet corn; correction of the commodity def inition for lima bean; increasing the tolerance for residues in/on ruminant meat byproducts and revocation of the

tolerance for residues in/on p oultry meat byproducts and eggs based on the results of new livestock feeding studies, and increasing the tolera nce for residues in/on wheat grain in order to harmonize with the Codex MRL. HED previously recommended for establishment of tolerances for residuesDimethoate Human Health Risk Assessment DP No. D416010

Page 10 of 104 

### in/on alfalfa seed and cotton gin byproducts and revisions to the tolerances for residues in/on

livestock commodities (M. Sahafeyan ; 24

- MAY

- 2011 ; D232849 ) and for establishment of

tolerances for residues in/on grass forage and hay (M. Sahafeyan ; 12

- NOV

- 2013 ; D239886 ). Additionally, the notation for blueberries in the e

- 40 CFR should be corrected to indicate t hat t here

are no U.S. registrations for blueberries as of August 16, 1996. Currently the e

- CFR omits the word

“no.”

2.3 Label Recommendations

No label recommendations have been identified

. A summary of the risk estimates has been provided, and shows that there are risk estimates of concern for registered uses of dimethoate based on the use information, label

- required personal protective equipment ( PPE; i.e., engineering controls), and REIs.

2.3.1 Recommendations from Residential Assessment

Adult der mal and children’s (1 to < 2 year old) dermal and incidental oral risk estimates from indirect exposure related to spray drift exceed HED’s LOC (MOEs < 100 0 ) at a range of

distan ces from the field depending on the spray

- drift scenario (e.g., 0 to >300 feet ) ( s ee Section 6.4.1)

. Appropriate drift reduction technologies such as changing the spray type/nozzle configuration to coarser spray applications may result in less drift and reduced risk concerns (i.e., higher MOEs) from aerial applications. Similarly, using coarser sprays and lowering boom height for groundboom sprayers reduces risk concerns.

3.0 Introduction

3.1 Chemical Identity

Table 3.1. Test Compound Nomenclature.

Chemical Structure

Empirical Formula C 5 H 12 NO 3 PS 2

Common Name Dimethoate

IUPAC name O,O

- dimethyl S

- methylcarbamoylmethyl phosphorodithioate or

2

- dimethoxyphosphinothioylthio

- N

- methylacetamide

CAS Name O,O

- dimethyl S

- [2

- (methylamino)

- 2

- oxoethyl] phosphorodithioate

CAS Registry Number 60

- 51

- 5

End

- use products Dimate 4E, Dimet hoate 4E, Cymate 267, Dimethoate 2.67 EC, etc.

Chemical Class OPDimethoate Human Health Risk Assessment DP No. D416010

Page 11 of 104 Table 3.1. Test Compound Nomenclature.

Chemical Structure

Empirical Formula C 5 H 12 NO 4 PS

Common Name Omethoate

IUPAC name O,O

- dimethyl S

- methylcarbamoylmethyl phosphorothioate

CAS Name O,O

- dimethyl S

- [2

- (methylamino)

- 2

- oxoethyl] phosphorothioate

CAS Registry Number 1113

- 02

- 6



### 3.2 Physical/Chemical Characteristics

Pure dimethoate is a colorless crystalline solid with an odor of mercaptan. Technical dimethoate (about 93% pure) varies from off

- white crystals to a grey semi

- crystalline material. Dimethoate is highly soluble in chloroform, methylene chloride, benzene, toluene, alcohols, esters, and ketones, slightly soluble in xylene, carbon tetrachloride, and aliphatic hydrocarbons, and partly

soluble in water (log K O W 

### = 0.70) with a vapor pressure of 1.85 x 10

- 6 

### mm Hg at 20 ° C. A table of physical/chemical properties for dimethoate can be found in Appendix E

.

3.3 Pesticide Use Pattern

There are numerous end

- use product labels registered with dimethoate as the active ingredient including liquid and WSP formulations. The labeled use sites include various agricultural crops,

Christmas tree farms

, trees grown for pulp, and ornamentals in o utdoor nurseries . Most of the registered products are applied via aerial, chemigation, airblast, groundboom

, or with handheld equipment. For most use sites/crops, the maximum application rate is 2 lb ai/A, but for ornamentals in outdoor nurseries, the ma ximum application rate is 4.15 lb ai/A for airblast applications specifically. A summary of registered labels and dimethoate use directions are

included in Appendix F

.

3.4 Anticipated Exposure Pathways

Humans may be exposed to dimethoate

, and its metabolite omethoate, in food and drinking water, since dimethoate may be applied directly to growing crops and application may result in

dimethoate reaching sources of drinking water. There are no residential uses of dimethoate ; however, there is the potential for short

- term non

- occupational exposure (dermal and incidental oral) to dimethoate and omethoate as a result of spray drift.

Based on the registered use pattern for dimethoate, short

- and intermediate

- term dermal and inhalation exposures are anticipated for occupational handlers and post

- application workers. Occupational handlers are anticipated to be exposed to the parent, dimethoate, only. Occupational post

- application workers may be exposed to residues of both dimethoate and

omethoat e

3.5 Consideration of Environmental JusticeDimethoate Human Health Risk Assessment DP No. D416010

Page 12 of 104 

### Potential areas of environmental justice concerns, to the extent possible, were considered in this human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions

to Address Env ironmental Justice in Minority Populations and Low

- Income Populations," ( http://epa.gov/compliance/ej/resources/policy/exec_order_12898.pdf ). As a part of every pesticide risk assessment, OPP considers a large variety of consumer subgroups according to

we ll

- established procedures. In line with OPP policy, HED estimates risks to population subgroups from pesticide exposures that are based on patterns of that subgroup’s food and water consumption, and activities in and around the home that involve pesticide use in a residential setting

. Extensive data on food consumption patterns are compiled by the USDA under the NHANES/WWEIA and are used in pesticide risk assessments for all registered food uses of a pesticide. These data are analyzed and categorized by subgroups based on age and ethnic group. Additionally, OPP is able to assess dietary exposure to smaller, specialized subgroups and exposure assessments are performed when conditions or circumstances warrant

. Whenever appropriate, non

- dietary exposures b ased on home use of pesticide products and associated risks for adult applicators and for toddlers, youths, and adults entering or playing on treated areas

post

- application are evaluated

. Further considerations are currently in development as OPP has

comm itted resources and expertise to the development of specialized software and models that consider exposure to bystanders and farm workers as well as lifestyle and traditional dietary patterns among specific subgroups.

4.0 Hazard Characterization and Dose

- Response Assessment

Dimethoate is a member of the OP class of pesticides. Like other OPs, the initiating event in the

AOP/ MOA, for dimethoate inv olves inhibition of the enzyme AChE via phosphorylation of the

serine residue at the active site of the enzyme. Dimethoate must be metabolized (activated) to

the oxon metabolite (omethoate), which is the active AChE inhibiting moiety. This inhibition leads to accumulation of acetylcholine and ultimately to neurotoxicity in the central and/or peripheral ner vous system (see Figure 1)

. For dimethoate and omethoate, AChE inhibition is the most sensitive endpoint in the toxicology database in multiple species, durations, lifestages, and routes. AChE inhibition is the focus of this hazard characterization; the availability of reliable AChE inhibition dose response data is one of the key determinants in evaluating the toxicology

database.

Figure 1. A OP for OPs

.

4.1 Toxicology Studies Available for Analysis

The toxicology database for dimethoate is complete for risk assessment. The acceptable

dimethoate studies available for risk assessment include:

 subchronic oral toxicity studies in rats and dogs 

# Target

Tissue


# Dose Phosphorylation

of the active site
of AChE Neurotoxicity

Accumulation
of acetylcholineDimethoate Human Health Risk Assessment DP No. D416010

Page 13 of 104 

###  chronic oral toxicity studies in rats and dogs

 carcinogenicity studies in rats and mice

 developmental studies in rats and rabbits

 reproduction toxicity study in rats

 acute and subchronic neurotoxicity studies in rats

 developmental neurotoxicity (DNT) study in rats

 acute and repeated comparative cholinesterase assays (CCA) in juvenile and adult

rats

 special cross

- fostering study in rats

 delayed neurotoxicity study in hens

 subchronic dermal toxicity stu dy in rats

 in vivo dermal penetration studies in rats

 immunotoxicity study in mice

 mutagenicity studies

 metabolism studies in rats

Although never registered as an active ingredient in the U.S., omethoate has in the past been registered in other count ries and, as a result, there is an extensive toxicity database for omethoate. The acceptable omethoate studies available for risk assessment include:

 chronic oral toxicity studies in rats and dogs

 carcinogenicity studies in rats and mice

 developmental studies in rats and rabbits

 reproduction toxicity studies in rats

 acute neurotoxicity study in rats

 acute and repeated CCA studies in rats

 special studies investigating AChE inhibition in rats and dogs

 delayed neurotoxicity study in hens

 repeated dosing inhalation study in rats

 mutagenicity studies

 metabolism studies in rats

Additionally studies have also b een submitted demonstrating no significant AChE inhibition from multiple degradates of dimethoate, including hydroxy dimethoate, O

- de smethyl omethoate carboxylic acid, des

- o

- methyl isodimethoate, O

- desmethyl omethoate, and dimethoate carboxylic

acid

.

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

4.2.1 Dimethoate

Dimethoate, like some other OPs, requires metabolic activ ation to its oxon metabolite ( omethoate ) to inhibit AChE, with subsequent metabolism that leads to detoxification. Generally, absorption and distribution are rapid with extensive metabolism and no accumulation

in the tissues.Dimethoate Human Health Risk Assessment DP No. D416010

Page 14 of 104 

### In a rat metabolism study, rats were administered [ 14 

### C]

- dimethoate as a single oral dose (10 or 100 mg/kg), an intravenous dose (10 mg/kg), or 14

- day repeated oral doses of dimethoate at 10 mg/kg followed by a single oral dose of [ 14 

### C]

- dimethoate at 10 mg/kg. Dimethoate was rapidl y absorbed, metabolized, and eliminated in rats for all dosing regimens. Consistent with the results of the AChE studies, there were no remarkable sex

- , dose

- , or treatment

- related differences in the absorption, distribution, and elimination of dimethoate in rats. Dimethoate was absorbed and distributed quickly with time to peak plasma concentrations (T
max 

### ) reached less than 1 hour post

dosing. Total recovery of radioactivity ranged between 91% and 97% of the administered dose. Most of the radioactivity was excreted via the urine (85

- 91% of the dose). A small amount of radioactivity was found in feces (1

- 2% of the dose), in the tissues and remaining carcass ( 1

- 2% of the dose), and in the expired air as carbon dioxide (2

- 3% of the dose).

In the rat, dimethoate is metabolized via hydrolytic and oxidative pathways (based on urine analyses). The hydrolytic pathway (major) involves cleavage of the C

- N bond to y ield dimethoate carboxylic acid that was subsequently metabolized to dimethyldithiophosphate, dimethylthiophosphoric acid, and dimethylphosphoric acid. A minor metabolic pathway involves oxidation of dimethoate to its oxon analogue, omethoate, which was s ubsequently metabolized to dimethylthiophosphoric acid and dimethylphosphoric acid. Loss of the methoxy groups of the parent to yield carbon dioxide is a minor metabolic pathway.

4.2.2 Omethoate

In a rat metabolism study with omethoate, male and female rats exhibited signs of toxicity, including trembling, salivation, high breathing rate, and congestion of the eyes, at 0.5

- 4 hours

post

- dosing. Overall recovery of administered radioactivity was 88

- 98%. There were no

remarkable sex

- , dose

- , or treatment

- related differences in the absorption, distribution, and elimination of omethoate in rats. Absorption rates were rapid and T
max 

### was reached within 1 hour post

- dosing. Omethoate was excreted within 48 hours with the majority excreted via the urine (85

- 97% of the administered dose). The remainder of the administered radioactivity was excreted via the feces (2

- 4% of the administered dose). Biliary excretion was found to account for the majority of the fecal metabolite content. Based upon tissue burden dat a, omethoate and/or its metabolites do not appear to undergo any significant sequestration.

Omethoate appeared to be metabolized to a greater extent in males than in females as evidenced by higher percentages of parent compound remaining in urine from fem ales and a higher percentage of omethoate metabolites in urine of males. The metabolite profile for urine included the parent compound (26

- 62% of the administered dose), N

- methyl

- 2

- ( methylsulfinyl )

- acetamide (16

- 35% of the administered dose)

, and O

- desmet hylated omethoate (4

- 9% of the administered dose). The same metabolites were also identified in the feces.

4.2.3 Dermal Absorption

There are two acceptable in vivo dermal penetration rat studies in the database for dimethoate. In the first study (MRID 43964001), dermal absorption (based on total amount of radioactivity recovered from urine, tissues, and feces after 6 hours of dermal exposure) was estimated to be 8

- 1 1% and 1

- 2% of the administered dose from rats treated at 10 and 100 mg/kg, respectively.

There were no sex

- related differences observed in absorption patterns. In the second study (MRID 45530501), dermal absorption (based on excreta, cage wash, and carc ass) was estimatedDimethoate Human Health Risk Assessment DP No. D416010

Page 15 of 104 

### at doses of 0.67 and 13.3 mg/kg to be approximately 6% after 1 hour of exposure and 25

- 38%

after 10

- 24 hours of exposure. Since a route

- specific dermal toxicity study was selected as the endpoint for dermal exposure assessments (see Sec tion 4.5.1), a dermal absorption factor is not

needed for this risk assessment.

4.3 Toxicological Effects

Dimethoate and omethoate have high

- quality dose

- response data across multiple lifestages, durations, and routes for both RBC and brain AChE inhibition. Many of these studies have been evaluated using BMD modeling techniques. BMD estimates are similar across age, sex, and method of administration (gavage, feeding, drinking water) for dimethoate and omethoate (Appendix 9 of USEPA 2004). High

- quality studies in the dermal and inhalation routes with dimethoate and omethoate, respectively, allow for route

- specific evaluation.

Using AChE inhibition as the critical endpoint for risk assessment purposes protects for other cholinergic effects, suc h as clinical signs, which are seen at doses much higher than those causing inhibition of AChE. In the case of dimethoate and omethoate, brain AChE inhibition provides the basis for human health risk extrapolations with the rat being the most sensitive

sp ecies for dimethoate and omethoate exposures. Details of numerous dimethoate studies can be found in the toxicology disciplinary chapter for the Reregistration Eligibility Document ( RED; P. Chin, 0 4

- MAR

- 1997; D229308). R elevant omethoate studies are summ arized in a 2005 review (P. Chin; 31

- MAY

- 2005; TXR# 0051425).

In the acute and repeated CCA studies, juvenile rats, pregnant dams, fetuses and non

- pregnant adults displayed similar results in both blood and brain measurements. In developmental and

repr oduction toxicity studies, AChE inhibition in fetuses/ offspring was seen at or above dose levels eliciting inhibition in parental animals

.

Increased qualitative susceptibility to offspring was observed in the toxicological databases

. Several studies (i.e., range

- finding and main DNT, cross

- fostering , and one

- generation reproductive toxicity studies with dimethoate, as well as the omethoate reproductive toxicity studies) demonstrate increased pup mortalit y following maternal exposure ; h owever, the

i ncreased pup mortality occurred at doses at or above those causing decreased brain AChE activity in parental animals. The underlying basis of pup mortality is not fully understood though and the available data do not support maternal toxicity as being the only determinant of pup mortality. The pup mortality has been extensively reviewed by OPP and the Office of Research and Development (ORD) along with the Federal Insecticide, Fungicide, and Rodenticide Act ( FIFRA ) Scientific Advisory Panel ( SAP). A more detailed discussion of the pup mortality observations can be found in the revised p ost

- SAP HED Chapter of the RED (D325201; 31

- JAN

- 2006).

It has been concluded that regulation of dimethoate exposure at levels below those causing brain

AChE i nhibition will protect against brain AChE inhibition, as well as increased pup mortality, based on the following:

1) Comparison of benchmark dose levels for brain AChE inhibition and pup mortality following repeated dosing indicates that AChE inhibition occu rs at doses similar to those associated with increases in pup mortality.Dimethoate Human Health Risk Assessment DP No. D416010

Page 16 of 104 

### 2) The evaluation of pup mortality data from the cross

- fostering study reveals that increases in mortality from short

- term exposures (10

- 15 doses) only occurred at the highest dose tes ted, indicating that increased mortality at lower doses requires longer

durations of repeated dosing. 3) Comparison of the no

- observed adverse

- effect level (NOAEL) for increased pup mortality to the BMD 10 

### for brain AChE inhibition following a single dose in dicates that brain AChE inhibition occurs at doses below those causing a clear increase in pup mortality.

These conclusions regarding the interpretation of pup mortality seen in the dimethoate and omethoate database were supported by the 2005 FIFRA SAP. The SAP further supported the use of brain AChE inhibition for deriving PODs as protective of the pup mortality.

Dimethoate is classified as having low acute toxicity via the oral, dermal, and inhalation routes ( Toxicity Category III or IV). It was foun d to be a moderate eye irritant, but not a dermal irritant

or dermal sensitizer. Omethoate is classified as acutely toxic via the oral, dermal, and inhalation routes ( Toxicity Category I or II).

There was no evidence of immunotoxicity up to 36 mg/kg/day in a recently submitted immunotoxicity study with dimethoate (MRID 48572807 and 48997901).

Dimethoate is classified as a Group C carcinogen

- possible human carcinogen ( Memo; K. Dearfield; 29

- AUG

- 1991). The classification is based upon equivocal hemolymp horeticular tumors in male B6C3F1 mice, the compound

- related (no dose response) weak effect of combined spleen (hemangioma and hemangiosarcoma), skin (hemangiosarcoma), and lymph (angioma and angiosarcoma) tumors in male Wistar rats, and positive mutagenic activity associated with

dimethoate. On June 25, 1992, the FIFRA SAP concurred with the Agency's classification of dimethoate as a Group C carcinogen. The Agency determined that quantification of risk using a

non

- linear approach would adequately account for all chronic toxicity, including carcinogenicity that could result from exposure to dimethoate.

4.3.1 Critical Durations of Exposure

One of the key elements in risk assessment is the appropriate integration of temporality between the exposure and hazard assessments. One advantage of an AOP understanding is that human health risk assessments can be refined, focused on the most relevant durations of exposure. The following text provides an analysis of the temporal pattern of AChE inhibition from acute (single) and repeated

- dosing studies in laboratory animals for dimethoate. This analysis provides the basis for determining which exposur e durations are appropriate for assessing human health risk. Table 4.3.1.1 provides a summary of the selected results from experimental toxicology

studies with dimethoate.

Table 4.3.1.1. Dimethoate BMD 10 and BMDL 10 Results (mg/kg/day) for Brain AChE Inhibition Over Time

in Adult Rats

.

Days of Dosing Males Females

BMD 10 BMDL 10 BMD 10 BMDL 10

1 a 2.5 1.7 2.2 1.3

11 a 0.49 0.37 0.37 0.27Dimethoate Human Health Risk Assessment DP No. D416010

Page 17 of 104 14 a NA NA 0.34 0.28

91 b 0.40 0.29 0.48 0.40

205 c 0.34 0.19 0.45 0.25

BMD 10 = estimated dose where AChE is inhibited by 10% compared to background

. BMDL 10 = lower confidence bound on the BMD 10

. NA = not applicable; measurements at this time point were for pregnant females on gestational day 20

.

a MRID 45529702

- CCA study

. b MRID 46348201

- One

- generation range finding study

.

c MRID 46181001

- Two

- generation reproduction toxicity study

.



### As shown in Table 4.3.1.1, the acute (single

- day ) BMD values are the largest in the table, whereas BMD values from repeated exposures are remarkably similar. Although studies with AChE measurements were more limited with omethoate, a similar pattern was observed. OPs exhibit a phenomenon known as steady

- state AChE inhibition. After repeated dosing at the same dose level, the degree of inhibition comes into equilibrium with the production of new, uninhibited enzyme. At this point, the amount of AChE inhibition at a given dose remains

consistent across d uration. In general, OPs reach steady

- state within 2

- 3 weeks, but this can vary among OPs. In the case of dimethoate, the results in Table 4.3.1.1 show a clear pattern of steady

- state reached by 11 days of exposure. Given the results in Table 4.3.1.1 fo r dimethoate, acute ( single

- day) and steady

- state durations are appropriate for human health risk assessment. As such, the endpoint selection discussed below focuses on acute ( single

- day) effects and steady

state effects.

Although there are data at a shorter time period than 21 days (i.e., 11 days), exposure assessments of 21 days and longer will be conducted for all routes of exposure (i.e., oral, dermal and inhalation) for all single chemical OP assessments. Although the durations of the toxicity and exposure assessments may differ, an exact match is not necessary and would suggest a level of precision that the toxicity data do not support. Given this, the 21

- day and longer exposure assessment is scientifically supportab le and also provides consistency with the OP cumulative

risk assessment (OP CRA; 2002, 2006) and across the single chemical risk assessment for the

OPs.

4.4 Literature Review on Neurodevelopment Effects

For the OPs, historically the Agency has used inh ibition of AChE as the POD for human health risk assessment; at present time, this policy continues. This science policy is based on decades of work which shows that AChE inhibition is the initial event in the pathway to acute cholinergic neurotoxicity. The use of AChE inhibition data for deriving PODs was supported by the FIFRA SAP (2008, 2012) for chlorpyrifos as the most robust source of dose

- response data for extrapolating risk and is the source of data for PODs for dimethoate /omethoate . A detailed

r eview of the epidemiological studies used in this review can be found either in the 2014 chlorpyrifos revised draft human health risk assessment (D. Drew; 29

- DEC

- 2014; D424485) or in the 2015 literature review for other organophosphates (OPP/USEPA; 15

- SEP

- 2015; D331251).

Newer lines of research on OPs in the areas of potential AOPs, in vivo animal studies, and notably epidemiological studies in mothers and children, have raised some uncertainty about the agency’s risk assessment approach with regard to t he potential for neurodevelopmental effects in fetuses and children. Many of these studies have been the subject of review by the agency over the last several years as part of efforts to develop a risk assessment for chlorpyrifos (D. Drew;Dimethoate Human Health Risk Assessment DP No. D416010

Page 18 of 104 

### 29

- DEC

- 2014; D4 24485). Initially, t he agency focused on studies from three US cohorts: 1) The Mothers and Newborn Study of North Manhattan and South Bronx performed by the Columbia Children’s Center for Environmental Health (CCCEH) at Columbia University; 2) the

Mt. Si nai Inner

- City Toxicants, Child Growth and Development Study or the “Mt. Sinai Child Growth and Development Study;” and 3) the Center for Health Assessment of Mothers and Children of Salinas Valley (CHAMACOS) conducted by researchers at University of Calif ornia Berkeley. The agency has evaluated these studies and sought external peer review (FIFRA SAP reviews in 2008 and 2012; federal panel, 2013 3 

### ) and concludes they are of high quality. In the

three US epidemiology cohort studies, mother

- infant pairs were recruited for the purpose of studying the potential health effects of environmental exposures during pregnancy on subsequent child development. Each of these cohorts evaluated the association between prenatal chlorpyrifos and/or OP exposure (with adverse neurodevelopmental outcomes in children through age 7 years). For the 2014 chlorpyrifos revised human health risk assessment (D. Drew; 29

- DEC

2014; D424485) , EPA included epidemiologic research results from these three US prospective

birth cohort studies but primarily focused on the results of CCCEH since this cohort has published studies on the association between cord blood levels of chlorpyrifos and neurodevelopmental outcomes. The agency retained the FQPA 10X Safety Factor (SF) in the 2014 chlorpyrifos revised risk assessment, in large part, based on the findings of these studies.

In the 2015 updated literature review (OPP/USEPA; 15

- SEP

- 2015; D331251), the agency conducted a systematic review expanding the scope of the 2012/2014 review focused on US

co hort studies with particular emphasis on chlorpyrifos. The expanded 2015 review includes consideration of the epidemiological data on any OP pesticide, study designs beyond prospective cohort studies, and non

- U.S. based studies. The updated literature review identified seven studies

which were relevant (Bouchard et al., 2010; Fortenberry et al., 2014; Furlong et al., 2014; Guodong et al., 2012; Oulhote and Bouchard , 2013; Zha ng et al., 2014; Shelton et al., 2014).

These seven studies have been evaluated in context with studies from the 2012/2014 review (D.
Drew; 29

- DEC

- 2014; D424485) . Only a brief summary is provided below.

The OP exposure being assessed in many of these s tudies used concentrations of urinary dialkyl phosphate metabolites (DAPs) as the urinary biomarker. Total DAPs is a non

- specific measure of OP exposure and is the sum of six separate molecules

- three dimethyl alkylphosphate (DMAP) molecules of DMP, DMTP , DMDTP, and three diethyl alkylphosphate (DEAP) molecules of DEP, DETP, and DEDTP. Each metabolite is a breakdown product from multiple OPs (Table 4.4.1; CDC, 2008) 4 

### . Specifically, DMP, DMTP, and DMDTP are associated with 18, 13, and 5 OPs, whereas DEP, DETP, and DEDTP are associated with 10, 10, and 4 OPs, respectively. Thus, using urinary DAPs alone as an exposure measure, it is not possible to separate the exposure and associated effects for single, specific OPs.

Table 4.4.1.CDC Table of organopho sphate pesticides and their dialkyl phosphate metabolites (2008).

Pesticide DMP DMTP DMDTP DEP DETP DEDTP

Azinphos methyl X X X

Chlorethoxyphos X X Chlorpyrifos X X Chlorpyrifos methyl X X

3 http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

- OPP

- 2008

- 0850

- 0170

4 http://www.cdc.gov/nchs/data/nhanes/nhanes_03_04/l26opd_c_met_organophosphorus_pesticides.pdfDimethoate Human Health Risk Assessment DP No. D416010

Page 19 of 1 04 Coumaphos X X
Dichlorvos (DDVP) X

Diazinon X X Dicrotophos X

Dimethoate X X X

Disulfoton X X X

Ethion X X X

Fenitrothion X X

Fenthion X X Isazaphos

- methyl X X

Malathion X X X

Methidathion X X X Methyl parathion X X

Naled X Oxydemeton

- methyl X X

Parathion X X

Phorate X X X

Phosmet X X X Pirimiphos

- methyl X X Sulfotepp X X Temephos X X

Terbufos X X X Tetrachlorviphos X

Trichlorfon X
DMP = dimethylphosphate; DEP = diethylphosphate; DMTP = dimethylthiophosphate; DMDTP = dimethyldithiophosphate; DETP = diethylthiophosphate; DEDTP = diethyldithiophosphate.



### For studies which measured urinary 3,5,6

- trichloro

- 2

- pyridinol ( TCPy) (e.g., Fortenberry et al

. , 2014; Eskenazi e t al

. , 2007; Whyatt et al

. , 2009), this metabolite can be derived from chlorpyrifos, chlorpyrifos

- methyl, and the herbicide triclopyr. TCPy is also the primary environmental degradate of chlorpyrifos, chlorpyrifos

- methyl, and triclopyr; thus exposure can be found directly on food treated with these pesticides. CCCEH studies have largely used chlorpyrifos measured in cord blood as the specific biomarker (e.g., Lovasi et al

. , 2010; Whyatt

et al

. , 2004; Rauh et al

. , 2011). The CHARGE study (Shelton et al

. , 2015) did not measure biomarkers but instead used geospatial analysis to focus on the residential proximity to OP exposure using data from the California Department of Pesticide Regulation, with five OPs accounting for a total of 73% of the pesticide appli ed near residential settings (chlorpyrifos, acephate, diazinon, bensulide, and dimethoate).

Similarly, DAPs can be found directly on food following OP applications (Zhang et al, 2008; Chen et al, 2012). Specifically, studies have shown that DAPs may fo rm as environmental degradates from abiotic hydrolysis, photolysis, and plant metabolism (Zhang et al, 2008; Chen et al, 2012; Racke et al, 1994). Furthermore, since these DAPs are excreted more rapidly and extensively than the parent OPs (Zhang et al, 20 08; Forsberg et al, 2008), direct exposure to DAPs may lead to an overestimate of OP exposure when using urinary DAPs as a biomarker of OP exposure. The agency recognizes that this is a source of uncertainty when using DAPs for assessing OP exposure and w ill continue to monitor this issue in future assessments.

With respect to neurological effects near birth, the CHAMACOS and Mt. Sinai cohorts measured neurological effects at birth, and observed a putative association with total DEAP, total DMAP,

and to tal DAP exposure (Engel et al., 2007; Young et al., 2005)

. Similarly, a Chinese study (Zhang et al., 2014) reported statistically significant associations between total DEAPs, total DMAPs, and total DAPs from prenatal OP pesticide exposure and neonatal neurodevelopmentDimethoate Human Health Risk Assessment DP No. D416010

Page 20 of 104 

### assessed 3 days after birth. However, another cross

- sectional Chinese study, Guodong et al (2012), observed no association with urinary DAPs and a developmental quotient score for 23

- 25

month old children.

The 3 US cohorts (CCCEH, Mt. Sinai, CHAMACOS) ea ch reported evidence of impaired mental and psychomotor development, albeit not consistent by age at time of testing (ranging from 6 month to 36 months across the three cohorts). Attentional problems and ADHD were reported by three prospective cohorts [Ra uh et al, 2006; Eskenazi et al., 2007; Marks et al, 2010 ; and Fortenberry et al (2014)] investigators with additional support from a case control study, Bouchard et al. (2010). The exposure metric varied among these studies. Specifically, Fortenberry et al (2014) found suggestive evidence of an association with TCPy and ADHD in boys whereas statistically significant associations were observed by Rauh et al (2006) with chlorpyrifos exposure and ADHD

. Eskenazi et al (2007) reported associations with total DMAPs and total DAPs and ADHD; Marks et al (2010) reported associations with total DEAP, DMAP, and total DAP exposure and ADHD. In a national cross

- sectional study of Canadian

children , using 2007

- 2009 data for children age 6

- 11 years (Oulhote and Bouchar d , 2013), there were no overall statistically significant associations observed between child urinary DEAP, DMAP, or total DAP metabolite levels and parentally reported behavioral problems. In contrast, Bouchard et al. (2010), looking at U.S. children age 8

- 15 years in the 2000

- 2004 National Health and Nutrition Examination Survey (NHANES), observed a positive association between attention and behavior problems and total DAPs and DMAPs, but not DEAPs. As part of their analysis, Oulhote and Bouchard (2013) noted that their outcome assessment for behavioral problems may not have been as sensitive as Bouchard et al (2010), which may in part account for

the difference in the observed results from these studies.

In addition, the three US cohorts and the CHAR GE study have reported suggestive or positive associations between OP exposure and autism spectrum disorders (Rauh et al., 2006; Shelton et al., 2014; Eskenazi et al, 2007; Furlong et al., 2014). Specifically, Furlong et al (2014) documented suggestive ev idence of an association between total DEAP exposure and reciprocal social responsiveness among blacks and boys. Eskenazi et al (2007) reported a statistically significant association between pervasive developmental disorder (PDD) and total DAP

exposure, whereas Eskenazi et al (2010) reported non

- significant, but suggestive, increased odds of PDD of 2.0 (0.8 to 5.1; p=0.14). Rauh et al (2006) documented a significant association between PDD and specifically chlorpyrifos exposure. Both PDD and reciprocal social responsiveness are related to the autism spectrum disorder. Using a different exposure assessment method (geospatial analysis and residential proximity to total OP exposure), Shelton et al (2014) also showed statistically significant associations b etween total OP exposure and ASD. While these studies vary in the magnitude of the overall strength of association, they have consistently observed a positive association between OP exposure and ASD. Finally, CCCEH, Mt. Sinai, CHAMACOS have reported an i nverse relation between the respective prenatal measures of chlorpyrifos and intelligence measures at age 7 years (Rauh et al. ,2011; Engel et al.,
2011; Bouchard et al., 2011 )

.

Across the epidemiology database of studies, the maternal urine, cord blood, and other (meconium) measures provide evidence that expos ure did occur to the fetus during gestation but the actual level of such exposure during the critical window(s) of susceptibility is not known. While significant uncertainties remain about the actual exposure levels experienced by mothers and infant parti cipants in the children’s health cohorts, it is unlikely that these exposures resultedDimethoate Human Health Risk Assessment DP No. D416010

Page 21 of 104 

### in AChE inhibition. As part of the CHAMACOS study, Eskenazi et al. (2004) measured AChE activity and showed that no differences in AChE activity were observed. The bio marker data (chlorpyrifos) from the Columbia University studies are supported by the agency’s dose reconstruction analysis using the PBPK

- PD model (D424485, D. Drew et al, 12/29/2014)

. Following the recommendation of the FIFRA SAP (2012), the agency condu cted a dose reconstruction analysis of residential uses available prior to 2000 for pregnant women and young

children inside the home. The PBPK

- PD model results indicate for the highest exposure considered (i.e., indoor broadcast use of a 1% chlorpyrifos formulation) <1% RBC AChE inhibition was produced in pregnant women. While uncertainty exists as to actual OP exposure at (unknown) critical windows of exposure, EPA believes it is unlikely individuals in the epidemiology studies experienced RBC AChE inhi bition.

A review of the scientific literature on potential modes of action/adverse outcome pathways (MOA/AOP) 5 

### leading to effects on the developing brain was conducted for the 2012 FIFRA SAP meeting (USEPA, 2012) and updated for the December 2014 chlorpyr ifos revised risk assessment (D. Drew; 29

- DEC

- 2014; D424485). In short, multiple biologically plausible hypotheses and pathways are being pursued by researchers that include targets other than AChE inhibition, including cholinergic and non

- cholinergic sys tems, signaling pathways, proteins, and others. However, no one pathway has sufficient data to be considered more credible than the

others. The fact that there are, however, sparse AOP data to support the in vitro to in vivo extrapolation, or the extrapolation from biological perturbation to adverse consequence significantly limits their quantitative use in risk assessment. The SAP concurred with the agency in 2008 and 2012 about the lack of definable key events in a MOA/AOP leading to developmental neurobehavioral effects. However, since the 2014 literature review, there are no substantive changes in the ability to define and quantitate steps in an MOA/AOP leading from exposure to effects on the developing brain. Published and submitted guideline DNT laboratory animal studies have been reviewed for OPs as part of the 2012/2014 review (D424485, D. Drew et al, 12/29/2014) and the updated 2015 review (OPP/USEPA; 15

- SEP

- 2015; D331251). Neurobehavioral alterations in laboratory animals were often reported, albeit at AChE inhibiting doses, but there was generally a lack of consistency in terms of pattern, timing, or dose

- response for these effects, and a number of studies were of lower quality. However, this information does

pro vide evidence of long

- lasting neurodevelopmental disorders in rats and mice following gestational exposure.

At this time, a MOA(s)/AOP(s) has/have not been established for neurodevelopmental outcomes. This growing body of literature does demonstrate, however, that OPs are biologically active on a number of processes that affect the developing brain. Moreover, there is a large body of in vivo laboratory studies which show long

- term behavioral effects from early life exposure, albeit at doses which cause AChE inhibition. EPA considers the results of the toxicological studies relevant to the human population, as qualitatively supported by the results of epidemiology studies. The agency acknowledges the lack of established MOA/AOP pathway and uncertainties associated lack of ability to make strong causal linkages and unknown window(s) of susceptibility. These unce rtainties do not undermine or reduce the confidence in the findings of the epidemiology studies. The epidemiology studies reviewed in the 2012/2014 and 2015 literature reviews represent different investigators, locations, points in time, exposure assessme nt procedures, and outcome measurements. Despite all these differences in study design, with the

5 Mode of action (MOA) and adverse outcome pathways (AOPs) describe a set of measureable key events that make up the biological processes leading to an adverse outcome and the causal linkages between such events.Dimethoate Human Health Risk Assessment DP No. D416010

Page 22 of 104 

### exception of two negative studies in the 2015 literature review (Guodong et al, 2012; Oulhote

and Bouchard , 2013), authors have identified associations with n eurodevelopmental outcomes associated with OP exposure across four cohorts and twelve study citations. Specifically, there is evidence of delays in mental development in infants (24

- 36 months), attention problems and autism spectrum disorder in early child hood, and intelligence decrements in school age children who were exposed to OPs during gestation. Investigators reported strong measures of statistical association across several of these evaluations (odds ratios 2

- 4 fold increased in some instances),

and observed evidence of exposures

- response trends in some instances, e.g. , intelligence

measures.

As section 408(b)(2)(C) of the FFDCA instructs EPA, in making its “reasonable certainty of no harm” finding, that in “the case of threshold effects, an additio nal tenfold margin of safety for the pesticide chemical residue and other sources of exposure shall be applied for infants and children

to take into account potential pre

- and postnatal toxicity and completeness of data with respect to exposure and toxicit y to infants and children .” Section 408 (b)(2)(C) further states that “the Administrator may use a different margin of safety for the pesticide chemical residue only if, on the basis of reliable data, such margin will be safe for infants and children.” Gi ven the totality of the evidence, there is sufficient uncertainty in the human dose

- response relationship for neurodevelopmental effects which prevents the agency from reducing or removing the statutory 10X FQPA Safety Factor. For the dimethoate DRA, a va lue of 10X has been applied. Similarly, a database uncertainty factor of 10X will be retained for occupational risk assessments. The agency will continue to evaluate the epidemiology studies and pursue approaches for quantitative

or semi

- quantitative com parisons between doses which elicit AChE inhibition and those which are associated with neurodevelopmental outcomes prior to a revised human health risk

assessment.

4.5 Safety Factor for Infants and Children (FQPA SF)

As noted above, the lack of an est ablished MOA/AOP makes quantitative use of the epidemiology studies in risk assessment challenging, particularly with respect to determining

dose

- response, critical duration of exposure, and window(s) of susceptibility. However, exposure levels in the ra nge measured in the epidemiology studies are likely low enough that they are unlikely to result in AChE inhibition. Epidemiology studies consistently identified associations with neurodevelopmental outcomes associated with OP exposure such as delays in

m ental development in infants (24

- 36 months), attention problems and autism spectrum disorder in early childhood, and intelligence decrements in school age children. Therefore, there is a need to protect children from exposures that may cause these effects ; this need prevents the agency from reducing or removing the statutory FQPA Safety Factor. Thus, the FQPA 10X Safety

Factor will be retained for dimethoate /omethoate for the population subgroups that include infants, children, youths, and women of childb earing age for all exposure scenarios.

4.5 .1 Completeness of the Toxicology Database

The existing toxicological database s are complete and adequate for characterizing dimethoate and omethoate toxicity. Available dimethoate studies for FQPA evaluation include developmental studies in the rat and rabbit, reproductive toxicity studies, CCA studies, neurotoxicity studies (acute, su bchronic, and developmental), and a special cross

- fostering study.Dimethoate Human Health Risk Assessment DP No. D416010

Page 23 of 104 

### Available omethoate studies for FQPA evaluation include CCA studies, developmental studies in the rat and rabbit, reproductive toxicity studies, and an acute delayed hen neurotoxicity stud y.

As discussed in Section 4.4, there is uncertainty in the human dose

- response relationship for neurodevelopmental effects and this warrants retention of the FQPA Safety Factor for the population subgroups that include infants, children, youths, and wome n of childbearing age for all exposure scenarios.

4. 5 .2 Evidence of Neurotoxicity

Dimethoate and omethoate are OPs with an established neurotoxic AOP. AChE inhibition is the most sensitive effect in all species, routes, and lifestages and is being used in deriving the PODs.

4.5 .3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal

There is no evidence of increased quantitatively sensitivity/susceptibility to offspring following exposure to dimethoate/omethoate based on AChE inhib ition. In some studies, increased pup mortality was observed at doses causing decreased brain AChE activity in parental animals indicating increased qualitative susceptibility. Regulation of dimethoate exposure at levels below those causing brain AChE in hibition will protect against brain AChE inhibition in adults and offspring, as well as the observed increase in pup mortality (see Section 4.3).

As discussed in Section 4.4, there is uncertainty in the human dose

- response relationship for neurodevelopme ntal effects and this warrants retention of the FQPA Safety Factor for the population subgroups that include infants, children, youths, and women of childbearing age for all exposure scenarios.

4.5 .4 Residual Uncertainty in the Exposure Database

There are no residual uncertainties with regard to dietary and occupational exposure assessments

. T he dietary exposure assessments use PDP data, PCT estimates, empirical and default processing factors, cooking factors derive d from literature studies, and the ac ute and steady

- state TAFs which account for the greater toxicity of the omethoate metabolite. The food and water dietary assessments incorporate 29 years of modeled water residues which assume 100% conversion of dimethoate to omethoate and were adjusted u sing the acute and steady

- state TAFs. Although data were used to refine the dietary exposure assessments, the assessments are not expected to underestimate dietary (food and water) exposures.

4.5 Toxicity Endpoint and Point of Departure Selections

4.5 .1 Dose

- Response Assessment

Table 4.5.4.1 summarizes the dimethoate toxicity endpoints and PODs selected from an evaluation of the database. This endpoint selection was based on a weight of the evidence evaluation using the following considerations:

 Rel ative sensitivity of the brain and RBC compartments : For dimethoate and omethoate, across most studies, durations, lifestages, and routes, the brain is similarly or moreDimethoate Human Health Risk Assessment DP No. D416010

Page 24 of 104 

### sensitive than RBCs. As such, OPP has emphasized the brain data in POD derivation as these data represent the target tissue and brain data tend to be less variable than RBC

data.

 Potentially susceptible populations (fetuses, juveniles, pregnancy ): The available AChE data across multiple lifestages (adults, pregnant adults, fetuses, juven iles) show no quantitative lifestage sensitivity for dimethoate and omethoate. In several studies, increased pup mortality was observed at doses at or above those causing decreased brain AChE activity in parental animals

.

 Route of exposure: It is preferred to match, to the degree possible, the route of exposure in the toxicity study with that of the exposure scenario(s) of interest. There are oral and dermal studies with dimethoate, as well as an inhalation study with omethoate, which

contai n high

- quality dose

- response AChE data.

 Duration of exposure: It is preferred to match, to the degree possible, the duration of toxicity study with that of the exposure duration of interest. There are single

- day and steady

- state oral studies, but only st eady

- state dermal and inhalation studies are available

.

 Consistency across studies: In cases where multiple datasets are available for a single duration, it is important to evaluate the extent to which data are consistent (or not) across

studies. The d imethoate and omethoate databases have striking consistency across studies, which allows the PODs to be derived from multiple critical studies

, thereby increasing the confidence in such values.

Consistent with risk assessments for other AChE

- inhibiting compounds, OPP has used a benchmark response (BMR) level of 10% and has thus calculated BMD 10 

### and BMDL 10 

### values (See Appendix B for summary of OPP’s ChE policy). The BMD 10 

### is the estimated dose where AChE is inhibited by 10% compared to background. The B MDL 10 

### is the lower confidence

bound on the BMD 10 

### . As a matter of science policy, the Agency uses the BMDL, not the BMD, for use as the POD (USEPA, 2012). All BMD/BMDL modeling for all individual datasets was completed using USEPA BMD Software to fit an e xponential model to the data. BMD results

from the OP CRA (2002, 2006) were included in the endpoint selection weight

- of

- evidence

evaluation.

Studies used for endpoint selection are supported by the 2005 FIFRA SAP. BMD values for studies applicable to endpoints selection (dimethoate CCA, dimethoate dermal, and omethoate inhalation studies) were recalculated using up

- to

- date BMD software, which resulted in slight adjustments in the POD values derived from the acute dimethoate CCA study (MRID 45529702)

and the dimethoate dermal toxicity study (MRID 44999101). The TAFs for omethoate were derived using BMD 10 

### values (see Section 4.5.2)

. All remaining POD values did not change from

the RED. This approach is consistent with the OP CRA and the previous dimethoate RED document (C. Jarvis; 31

- JAN

- 2006; D325201).

Summary tables of BMD analyses can be found in Appendix C and the technical details of the analysis can be found in the BMD analysis memo (M. Perron; 15

- SEP

- 2015 ; TXR# 0057249 ).

Acute Dietary (all populations)

A POD for the acute dietary (all populations) exposure scenario was derived from the results of a high

- quality, well

- conducted dimethoate CCA rat study (MRID 45529702). A BMDL 10 

### of 0.91 mg/kg/day associated with brain AChE inhibition in PND11 female pups was selected as aDimethoate Human Health Risk Assessment DP No. D416010

Page 25 of 104 

### suitable POD for the acute dietary (all populations) exposure scenario. The corresponding

BMD 10 

### was 1.55 mg/kg/day.

Brain AChE inhibition was selected for the POD since the brain is a principal target organ for

OP pesticides and the brain AChE data was more robust than RBC AChE data. Data from the PND11 pups represent highly exposed sub

- populations (infants and young children) an d thus are appropriate for POD derivation.

An uncertainty factor of 100 0 X (10X to account for interspecies extrapolation, 10X for intraspecies variation , and 1 0 X FQPA SF due to uncertainty in the human dose

- response relationship for neurodevelopmental e ffects (see Section 4.4) ) is applied to the BMDL 10 

### to obtain

an aPAD of 0.00 0 9 1 mg/kg/day for exposure scenarios with infants, children, youths, and women of childbearing age

. The only population subgroup that the FQPA SF is not retained for

is adults 50

- 99; therefore, the aPAD for this population subgroup is 0.0091 mg/kg/day.

Steady

- State Dietary (all populations)

There is remarkable similarity in BMD estimates across multiple dimethoate studies, durations, lifestages, and compartments in studies 11 day s and longer (Table 4.3.1.1; Appendix 9 of USEPA 2004). Because of this consistency, OPP has elected to use BMD/BMDL estimates reported in the OP CRA (2002, 2006) for deriving the steady

- state oral POD. Results of the OP CRA incorporate multiple time poi nts together in a single BMD/BMDL analysis and are thus highly robust. Specifically, in the OP CRA, EPA performed a sophisticated statistical analysis using nonlinear mixed effects models that allow for combining the results of multiple studies and multip le time points into a single BMD estimate. These procedures were reviewed favorably by the FIFRA SAP in February 2002.

For the OP CRA, the available AChE data for dimethoate at durations of 21 days and longer in

adult rats were extracted from the combi ned chronic oral toxicity/carcinogenicity study in rats (MRID 00164177). The plot of the brain AChE data from this study can be found in F igure

4.5.1.1. A BMDL 10 

### of 0.22 mg/kg/day associated with brain AChE inhibition in male and

female adult rats was selected as a suitable POD for the steady

- state dietary (all populations) exposure scenario. The corresponding BMD 10 

### was 0.25 mg/kg/day.

An uncertainty factor of 100 0 X (10X to account for interspecies extrapolation, 10X for intraspecies variation , and 1 0 X FQPA SF due to uncertainty in the human dose

- response relationship for neurodevelopmental effects (see Section 4.4 ) ) is applied to the BMDL 10 

### to obtain

a ssPAD o f 0.00 0 2 2 mg/kg/day for exposure scenarios with infants, children, youths, and women of childbearing age

. The only population subgroup that the FQPA SF is not retained for is adults

50

- 99; therefore, the ssPAD for this population subgroup is 0.0022 mg/kg/ day.

Figure 4.5.1 .1 . BMD Results (Red = males; Blue = females) from the OP CRA (2002, 2006)

for D imethoate ( e xtracted fr om USEPA, 2002, Appendix III.B )

.Dimethoate Human Health Risk Assessment DP No. D416010

Page 26 of 104 

### Incidental Oral, Steady

- State

For the purpose of assessing potential risk associated with incidental oral exposure from steady

state durations, OPP selected the dose and endpoint from the OP CRA , which is based on available AChE data for dimethoate at durations of 21 days and longer in adult rats from the combined chronic oral toxicity/carcinogenicity study in rats (USEPA, 2002 and 2006). Quantitation of incidental oral risks was performed using the BMDL 10 

### value of 0.22 mg/kg and

the BMD 10 

### of 0.25 mg/kg based on brain AChE inhibition

. These values do not specifically represent the subpopulations of interest (infants, toddlers, young children) for incidental oral exposure; however, there was no evidence of quantitative susceptibility in repeated dosing studies. A total uncertainty fact or of 100 0 X is appropriate for incidental oral exposures (10X for interspecies extrapolation, 10X f or intraspecies variation, and 1 0 X FQPA SF due to uncertainty

in the human dose

- response relationship for neurodevelopmental effects (see Section 4.4 ).

Dermal, Steady

- State

A dermal POD was selected from a 28

- day dermal dimethoate toxicity study (MRID 44999101) in rats based on brain AChE inhibition in female rats (BMDL 10 

### = 20.2 mg/kg/day; BMD 10 

### = 28.5 mg/kg/day). A total uncertainty factor of 100 0 X is appropriate for dermal exposures (10X for interspecies extrapolation, 10X for intraspecies variation, and a 1 0 X FQPA SF for residential

assessments or as a database uncertainty factor in occupational assessments due to uncertainty in

the human dose

- respons e relationship for neurodevelopmental effects (see Section 4.4 ).

Inhalation Steady

- State

A route

- specific inhalation toxicity study with dimethoate is not available to assess AChE inhibition due to repeated exposure. An inhalation POD was selected fro m a 28

- day inhalation toxicity study with omethoate (MRID 46358601) based on brain AChE inhibition in male rats (BMDL 10 

### = 0.38 mg/m 3 

### /day or 0.00038 mg/L/day; BMD 10 

### = 0.51 mg/m 3 

### /day or 0.00051Dimethoate Human Health Risk Assessment DP No. D416010

Page 27 of 104 

### mg/L/day). Due to the lack of characterization of particle size s in the study, the mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) could not be determined. As a result, human

- equivalent concentrations could not be estimated for the systemic effects (AChE inhibition) from inhalation expo sure. For occupational scenarios, duration adjustments were made to extrapolate exposure in the animal study (6 hours/day; 5 days/week) to a typical occupational exposure (8 hours/day; 5 days/week). The resulting duration adjusted value for occupational exposures is 0.285 mg/m 3



### . For estimating occupational inhalation risks from different occupational activities, inhalation doses of 0.016, 0.033, and 0.057 mg/kg/day corresponding to the breathing rates of 8 .3, 16.7, or 29 L/min were calculated using

this duration adjusted value. For inhalation exposures, a total uncertainty factor of 100 0 X was applied (10X for interspecies extrapolation, 10X for intraspecies variation, and a 1 0 X database uncertainty factor in occupational assessments due to uncertainty in the human dose

- response relationship for neurodevelopmental effects (see Section 4.4) )

.

4.5.2 Toxicity Adjustment Factors for Omethoate

As the oxon metabolite of dimethoate, omethoate has been found to be a more potent AChE

inhibitor. To account for th e increased potency of omethoate in risk estimates, BMD modeling was used to evaluate relative potency for dimethoate and omethoate and to estimate the TAFs for

acute and steady

- state exposure durations. As described in the guidance document for CRA (USEP A, 2002), comparisons of toxic potency should be made using a uniform basis of comparison, by using to the extent possible a common response derived from a comparable measurement methodology, species, and sex for all the exposure routes of interest. Dose

response modeling is preferred over the use of no

- or lowest

- observed adverse

- effect levels (NOAELs/LOAELs) for determining relative toxic potency. NOAELs and LOAELs do not necessarily reflect the relationship between dose and response for a given chemica l, nor do they reflect a uniform response across different chemicals.

TAFs have been estimated previously for dimethoate and omethoate (A. Lowit; 11

- APR

- 2005; TXR# 0052940). Updated acute TAFs were calculated since previous values were based only on the limited data available at that time . R ecently received omethoate CCA data can be incorporated into the acute analysis to derive sex

- and age

- specific values. To calculate acute
TAFs, BMD 10 

### values obtained from the acute CCAs in adult and juvenile rat s were utilized. The

sex

- and age

- specific acute TAF applied to residues of omethoate corresponds to the age and sex of the animal used for endpoint selection (i.e., the acute TAF of 8 will be used to assess acute dietary exposures because the POD value i s based on brain AChE inhibition in female PND11 pups).

The originally calculated steady

- state TAF of 3 was derived using the BMD 10 

### values from the combined chronic oral toxicity/carcinogenicity study for dimethoate and a 28

- day subchronic oral toxicity s tudy for omethoate (A. Lowit; 24

- APR

- 2002 ; TXR# 0050651 ). This value has

since been verified using data from a two

- year feeding study with omethoate; therefore

, no changes were made to the steady

- state TAF (A. Lowit; 10

- JUL

- 2002; TXR# 0050901)

.

Table 4.5.2.1. Acute TAFs a Calculated for Adult and Juvenile Rats Using BMD of Brain AChE Inhibition After a Single Dose

. Male FemaleDimethoate Human Health Risk Assessment DP No. D416010

Page 28 of 104 Adults

Dimethoate BMD 10 (mg/kg/day) 2.5 2.2

Omethoate BMD 10 (mg/kg/day) 0.2 0.3

Acute TAF 13 7
Pups (PND11)

Dimethoate BMD 10 (mg/kg/day) 1.8 1.6

Omethoate BMD 10 (mg/kg/day) 0.2 0.2

Acute TAF 9 8

a TAF = dimethoate BMD 10 ÷ omethoate BMD 10

.



### 4.5.3 Recommendation for Combining Routes of Exposures for Risk Assessment

When there are potential occupational and residential exposures to a pesticide, the risk assessment must address exposures from three major sources (oral, dermal, and inhalation) and determine whether the individual exposures can be combined if they have t he same toxicological

effects. PODs for the incidental oral, dermal, and inhalation routes are all derived from brain

AChE inhibition. As a result, exposure from all routes can be combined.

4.5.4 Cancer Classification and Risk Assessment Recommendation

Dimethoate is classified as a Group C carcinogen

- possible human carcinogen ( Memo; K. Dearfield; 29

- AUG

- 1991). On June 25, 1992, the FIFRA SAP concurred with the Agency's classification of dimethoate as a Group C carcinogen. Quantificati on of risk using a non

- linear approach will adequately account for all chronic toxicity, including carcinogenicity that could result from exposure to dimethoate.

4.5.5 Summary of Points of Departure and Toxicity Endpoints Used in Human Risk

Assessment

Table 4.5.5.1

. Summary of Toxicological Doses and Endpoints for Dimethoate for Use in Dietary and Non

- Occupational Human

Health Risk Assessments

. Exposure/

Scenario POD UFs a LOC Study and Toxicological Effects

Acute Dietary (all populations except adults 50

- 99 years old ) BMDL 10 =

0.91 mg/kg/day UF A = 10X

UF H = 10X FQPA SF = 1 0 X aRfD = 0.00 0 9 1

aPAD = 0.00 0 9 1 CCA study in rats

(MRID 45529702)

BMD 10 = 1.55 mg/kg/day

Inhibition of brain AChE in female rat pups

.

Acute Dietary (adults 50

- 99 years old) BMDL 10 =

0.91 mg/kg/day UF A = 10X

UF H = 10X FQPA SF = 1X aRfD = 0.0091

aPAD = 0.0091 CCA study in rats

(MRID 45529702)

BMD 10 = 1.55 mg/kg/day

Inhibition of brain AChE in female rat pups.

Steady

- State Dietary (all populations except adults 50

- 99 years old ) BMDL 10 =

0.22 mg/kg/day UF A = 10X

UF H = 10X FQPA SF = 1 0 X ssRfD = 0.00 0 2 2

ssPAD = 0.00 0 2 2 Combined chronic oral toxicity/carcinogenicity

study (OP CRA 2002, 2006; MRID 00164177)

BMD 10 = 0.25 mg/kg/day

Inhibition of brain AChE in adult rats

.Dimethoate Human Health Risk Assessment DP No. D416010

Page 29 of 104 Table 4.5.5.1

. Summary of Toxicological Doses and Endpoints for Dimethoate for Use in Dietary and Non

- Occupational Human

Health Risk Assessments

. Exposure/

Scenario POD UFs a LOC Study and Toxicological Effects

Steady

- State Dietary (adults 50

- 99 years old) BMDL 10 =

0.22 mg/kg/day UF A = 10X

UF H = 10X FQPA SF = 1X ssRfD = 0.0022

ssPAD = 0.0022 Combined chronic oral toxicity/carcinogenicity

study (OP CRA 2002, 2006; MRID 00164177)

BMD 10 = 0.25 mg/kg/day

Inhibition of brain AChE in adult rats.

Incidental Oral Steady

- State BMDL 10 =

0.22 mg/kg/day UF A = 10X

UF H = 10X FQPA SF = 1 0 X Residential LOC

for MOE < 100 0 Combined chronic oral toxicity/carcinogenicity

study (OP CRA 2002, 2006; MRID 00164177)

BMD 10 = 0.25 mg/kg/day

Inhibition of brain AChE in adult rats

.

Dermal Steady

State BMDL 10 =

20.2 mg/kg/day UF A = 10X

UF H = 10X FQPA SF = 10X Residential LOC

for MOE < 100 0 28

- day rat dermal toxicity

(MRID 44999101)

BMD 10 = 28.5 mg/kg/day

Inhibition of brain AChE in adult rats.
Cancer (oral, dermal, inhalation) Classification: Group C carcinogen (possible human carcinogen)

.

Point of d eparture (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. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = potential

varia tion in sensitivity among members of the human population (intraspecies). FQPA SF = FQPA Safety Factor. PAD = population adjusted dose (a = acute, ss = steady

- state ). RfD = reference dose (a = acute, ss = steady

- state ). MOE = margin of exposure. LOC = level of concern. BMD 10 = estimated dose where AChE is inhibited by 10% compared to background

. BMDL 10 = lower confidence bound on the BMD 10

.

a FQPA SF retained for infants, children, youths, and women of childbearing age for all exposure scenarios due to uncertainty in the human dose

- response relationship for neurodevelopmental effects (see Section 4.4). This includes all exposure scenarios, except the dietary exposure scenarios for the population subgroup adults 50

- 99 for which the FQPA SF has been re duced to 1X.

Table 4.5.5.2

. Summary of Toxicological Doses and Endpoints for Dimethoate for Use in Occupational Human Health

Risk Assessments

. Exposure/

Scenario POD UFs LOC Study and Toxicological Effects

Dermal Steady

State BMDL 10 =

20.2 mg/kg/day UF A = 10X

UF H = 10X

UF DB = 10X b Occupational

LOC for MOE <
100 0 28

- day rat dermal toxicity

(MRID 44999101)

BMD 10 = 28.5 mg/kg/day

Inhibition of brain AChE in adult rats.

Inhalation Steady

State BM D L 10 =

0.38 mg/m 3 /day a UF A = 10X

UF H = 10X

UF DB = 10X b Occupational

LOC for MOE <
100 0 Omethoate 21

- day inhalation rat study

(MRID 46358601)

BM D 10 = 0.51 mg/m 3 /day

Inhibition of brain AChE in adult rats.

Cancer (oral, dermal, inhalation) Classification: Group C carcinogen (possible human carcinogen).

Point of d eparture (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. UF = uncertainty factor . UF A = extrapolation from animal to human (interspecies). UF H = potential variation in sensitivity among members of the human population (intraspecies). MOE = margin of exposure. LOCDimethoate Human Health Risk Assessment DP No. D416010

Page 30 of 104 = level of concern. BMD 10 = estimated dose where AChE is inhibited by 10% compared to background

. BMDL 10 = lower confidence bound on the BMD 10

.

a Inhalation doses corresponding to the breathing rates of 8.3, 16.7, and 29 L/min were calculated as 0.016, 0.033, and 0.057 mg/kg/day, respectively, for occupational activities using a duration adjusted value of 0.285 mg/m 3

. b UF DB for occupational dermal and inhalation exposures = database uncertainty factor due to uncertainty in the

human dose

- response relationship for neurodevelopmental effects (see Section 4.4)



### 4.6 Endocrine Disruption

As required by FIFRA and the Federal Food, Drug, and Cosmetic Act (F FDCA ) , 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, neurotoxicity, developmental, reproductive, and general or systemic toxicity.

These studies include endpoints that may be susceptible to endocrine influence, including effects on endocrine target organ histopathology, organ weights, estru s cyclicity, sexual maturation, 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 diff erent ta xonomic groups

. As part of its r e registration decision for dimethoate, 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

secti on 408(p), dimethoate is subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).

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

- tiered approach to making the statutorily required

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal

systems

. Chemicals that go through Tier 1 screening and are found to have the potenti al to interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 testing is designed to identify any adverse endocrine

- related effects caused by the substance, and

establish a dose

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

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals

. Between October 2009 and February 2010, EPA issue d test orders/data call

- ins for the first group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. A second list of chemicals identified for EDSP screening was published on June 14, 2013 6 

### and includes some pesticides scheduled for Registration Review and chemicals found in water

. Neither of these lists should be construed as a list of known or likely endocrine disruptors.

Dimethoate is on List 1 for which EPA has received all the require d Tier 1 assay data. The Agency has review ed all of the assay data received for the appropriate List 1 chemicals and the

conclusions of those reviews are available in the chemical

- specific public dockets (see EPA

- HQ

OPP

- 2009

- 0059 ) . For further informatio n on the status of the EDSP, the policies and

6 See http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

- OPPT

- 2009

- 0477

- 0074 for the final second list of

chemicals.Dimethoate Human Health Risk Assessment DP No. D416010

Page 31 of 104 

### procedures, the lists of chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our website

. 7



### 5.0 Dietary Exposure and Risk Assessment

5.1 Metabolite/Degradate Residue Profile

5.1.1 Summary of Plant and Animal Metabolism Studies

The qualitative nature of the residue in plants is adequately understood. Dimethoate is readily taken up and translocated by plants, and is metabolized hydrolytic and oxidative processes to

om ethoate, dimethoate carboxylic acid, dimethyl hydrogen phosphate and O,O

- dimethyl hydrogen phosphorodithioate, indicating oxidation to omethoate, omethoate carboxylic acid, and dimethoate carboxylic acid, and cleavage of the P

- S linkage either before or af ter oxidation. The residues to be regulated in plants are dimethoate and its oxygen analog, omethoate. The current tolerance expression for plant commodities is adequate.

In the confined rotational crop study, a substantial proportion of the residue w as characterized as polar compounds or polar hydroxy compounds. Based on the current studies and registered rates, i nadvertent residues dimethoate and omethoate in rotational crops are expected to be

in significant; the low residue levels consisted mainly of polar metabolites.

The qualitative nature of the residue in eggs, poultry tissues, and ruminant tissue is adequately

understood. The available livestock metabolism data indicate that metabolism occurs via conversion of dimethoate to omethoate, follow ed by cleavage of the P

- S bond resulting in phosphorylation of natural products. The established tolerances for dimethoate residues in livestock commodities are currently expressed in terms of the total residues of dimethoate and its oxygen analog, ometho ate.

5.1.2 Summary of Environmental Degradation

Dimethoate is highly mobile and relatively non

- persistent. The primary route of dissipation is microbially mediated hydrolytic and oxidative degradation in aerobic soil, particularly under

moist conditio ns, with a half

- life of 2.2 days. Dimethoate does not photodegrade. Volatilization of dimethoate from the soil surface appears to be moderate and it is not expected to be a significant route of dissipation compared to other routes of dissipation. It hyd rolyzes very slowly in sterile buffered solutions at pHs 5 and 7 (156 and 68 days, respectively), but hydrolyzes rapidly to desmethyl dimethoate and dimethyl thiophosphoric acid with a half

- life of 4.4 days at pH 9. The anaerobic half

- life was found to be approximately 22 days, with the major

non

- volatile degradate being desmethyl dimethoate. Once dimethoate is applied by foliar application, it is expected to reach the crop, but it can also be transported offsite by spray drift and/or surface (dissolved) runoff occurring within days to weeks after applications. The chemical is not expected to leach substantially due to its relatively low persistence in soil. Dimethoate is systemic (although it also has contact activity), so it is also expected to move

th rough vegetation and/or root systems. The primary toxic degradate, omethoate, was found

under field conditions in the top layer (0

- 6”) of soil in all five field studies , though it was not

7 http://www.epa.gov/endo/Dimethoate Human Health Risk Assessment DP No. D416010

Page 32 of 104 

### detected in the laboratory degradation and/or soil and sediment met abolism studies . The presence of omethoate has been established through field studies in insects, plants, and

mammals. It is also formed during drinking water treatment. Omethoate was the only degradate analyzed in the dimethoate field

- dissipation study . The other degradates identified in the laboratory studies were not included in the analysis because it is believed that: 1) based on the aerobic soil metabolism study, they would not persist in the field; and, 2) they are not toxicologically significan t.

5 .1.3 Comparison of Metabolic Pathways

Extensive studies have been conducted on the metabolism of dimethoate in both plants and mammals. The major route of metabolism in mammals appears to be through the thiocarboxy derivative to the corresponding di methyl esters of phosphoric, thiophosphoric, or dithiophosphoric acids. The oxygen analog of dimethoate forms in animals, although this route is minor with respect to the principle route. In plants, the formation of the oxygen analog is a major route of metabolism. However, various investigators are not in agreement regarding the quantitative nature of this oxidation route, nor are they in agreement on quantitative nature of the other pathways of metabolism, which involve hydrolysis and demethylation.

5.1.4 Residues of Concern Summary and Rationale

The residue of concern in crops and livestock, for purposes of tolerance enforcement and risk

assessment are dimethoate ( dimethoate ( O

, O

- dimethyl S

- [2

- (methylamino)

- 2

- oxoethyl] phosphorodithioate) and omethoate, its oxygen analog, ( O

, O

- dimethyl S

- [2

- (methylamino)

- 2

- oxoethyl] phosphorothioate. The residues of concern in drinking water are dimethoate and

omethoate.

Table 5.1.4. Summary of Metabolites and Degradates to be included in the Risk Assessmen t and Tolerance Expression.

Matrix Residues included in Risk

Assessment Residues included in Tolerance Expression

Plants Primary Crop Dimethoate and o methoate Dimethoate and o methoate

Rotational Crop Dimethoate and o methoate Not Applicable

Livestock Ruminant Dimethoate and o methoate Dimethoate and o methoate

Poultry Dimethoate and o methoate Dimethoate and o methoate Drinking Water Dimethoate and o methoate Not Applicable



### Toxicological studies have been submitted for several dimethoate metabolites, including omethoate, hydroxy dimethoate, O

- desmethyl omethoate carboxylic acid, des

- o

- methyl isodimethoate, O

- desmethyl omethoate, and dimethoate carboxylic acid. Omethoate was the only metabolite that demonstrated significant inhibition of A ChE and is thus the only metabolite

of concern.

5.2 Food Residue Profile

H ED has previously evaluated residue data depicting the magnitude of dimethoate residues of concern in/on all registered crops. Quantifiable residues were found in crops with short pre

harvest intervals ( PHIs ; e.g., celery, beans, citrus), resulting in tol erance levels of up to 5.0 ppm in food commodities. Dimethoate was generally the major component of the total residue.Dimethoate Human Health Risk Assessment DP No. D416010

Page 33 of 104 

### Extensive USDA PDP monitoring data for residues of dimethoate and omethoate in numerous

commodities are available. The PDP was speci fically designed for risk assessment; analysts prepare samples in a manner similar to typical consumer practices, such as washing, coring/pitting, and/or peeling. The PDP samples are collected at large

- scal e distribution centers, just prior to sale in gro cery stores, and are more likely to reflect “dinner plate” residues. Previous dietary assessments for dimethoate have used FDA surveillance data; however, these data are considerably older than the available PDP data, and were not use d in this assessment. Dimethoate and/or omethoate residues were detected by PDP in the following commodities/processed foods with registered tolerances: potatoes without peel (2 detects/1544 samples); leaf lettuce (7 detects/782 samples); celery (253 detects/1480 samples); b roccoli (40 detects/1400 samples); cauliflower (9 detects/923 samples); kale (13 detects/802 samples); fresh green beans (84 detects/1480 samples); canned green beans (1 detect/928 samples); frozen green beans (8 detects/555 samples); fresh snap peas (420 detects/1487 samples); frozen sweet peas (90 detects/744 samples); fresh tomatoes (6 detects/1481 samples); canned tomatoes (1 detect/737 samples); bell peppers (80 detects/1671 samples); non

- bell peppers (90 detects/739 samples); cantaloupes (19 detects/1 482 samples); watermelons (15 detects/371 samples); tangerines (2 detects/1426 samples); pears (3 detects/1485 samples); cherries (1 detect/419 samples); blueberries (10 detects/1477 samples); and fresh asparagus (2 detects/1488 samples).

HED has eval uated residue data pertaining to the potential for concentration of dimethoate residues of concern in processed commodities. Significant concentration of residues was seen only in dried citrus pulp. PDP data are available for the following processed food s : tomato paste, canned tomatoes, orange juice, canned black, kidney, pinto, and garbanzo beans, canned peas, canned pears, and green bean, pea, and pear baby food . Residues of dimethoate and/or

omethoate were not detected in any sample, except as outlin ed above.

5.3 Water Residue Profile

The residues of concern in drinking water for purposes of risk assessment are dimethoate and

omethoate. EFED provided estimated drinking water concentrations (EDWCs) in the foll owing drinking water assessment: “Tier I I Drinking Water Assessment for Dimethoate for the Use in Human Health Risk Assessment in the Registration Review Risk Assessment (J. Me léndez, 28

- JUL

- 2014; D415002). The EDWCs were calculated using the Tier II Surface Water Concentration Calculator (SWCC ), the Tier II Pesticide Root Zone Model

- Groundwater (PRZM

GW), and the Tier I Screening Concentration in Ground Water (SCI

- GROW) models; however, dietary assessments were not completed using groundwater values since the peak EDWCs for groundwater were sub stantially lower than those for surface waters. Groundwater values and

characterization are summarized in the most recent dietary memo (J. Van Alstine; 15

- SEP

- 2015 ; D418590 ).

S urface water runs were initially performed at the maximum application rate and number of applications, minimum reapplication interval, and default national p ercent c ropped a rea (PCA; equal to 0.91 or 91% for agricultural crops and 1.0 or 100% for non

- agricultural uses) using the

Tier II SWCC model

. Preliminary dietary exposure assessments indicated that the maximum application rate EDWCs resulted in dietary exposure estimates that were above the LOC for many scenarios . Therefore, modeling with typical application rates and regional PCA for agricul tural uses was conducted to provide typical rate EDWCs for dietary assessments . NoDimethoate Human Health Risk Assessment DP No. D416010

Page 34 of 104 

### typical usage data were available for the non

- agricultural uses; therefore, typical non

- agricultural

scenarios were modeled with lower rates using a set of assumptions that are discussed in the

most recent drinking water memo (J . Meléndez, 28

- JUL

- 2014; D415002).

D aily time

- series outputs that simulate 29 years (1962

- 1990) of residues of dimethoate in surface drinking water for the 44 different scenarios were modeled using t he Tier II SWCC. These

scenarios were selected based on the use rates and encompass both maximum (24 scenarios) and typical (20 scenarios) application rates for agricultural and non

- agricultural uses of dimethoate. Additional details regarding the select ion of the scenarios can be found in the most recent drinking water memo ( J. Meléndez, 28

- JUL

- 2014; D415002)

. Since omethoate was not observed in the environmental fate studies in significant amounts, the omethoate e quivalent values were expressed based on its toxicity relative to dimethoate. All of the time

- series data were adjusted to reflect 100% conversion of dimethoate to omethoate 8 

### by multiplying the residues by the acute (8X) and steady

- state (3X) TAFs. Therefore, EFED provided a total of 88 distributions: 44 distributions that were adjusted using the acute TAF (“acute distributions”) and 44 distributions that were adjusted using the steady

- state TAF (“ steady

- state distributions”). No further adjustments were made to the acute distributio n files. Since the steady

- state average dietary assessments used 21

- day rolling averages for drinking water, the steady

- state distributions were further adjusted to be 21

- day rolling averages. In the 21

- day rolling average distributions, the first data p oint is the average of days 1

- 21, the second data point is the average of days 2

- 22, the third data point is the average of days 3

- 23, etc. The 21

- day rolling average continues until the last 20 days of residues of the final distribution year (1990). For these residues, the average was taken only of the remaining days, resulting in residue values that are

not 21

- day averages.

Summary tables for EDWCs using maximum and typical application rates can be found in Appendix H

.

5.4 Dietary Risk Assessment

H ighly refined a cute and steady

- state (two

- day average) dietary exposure and risk assessments for dimethoate and its metabolite omethoate were conducted using DEEM

- FCID Version 3. 1 8

. Th is model use s 2003

- 2008 food consumption data from USDA’s NHANES/WWEIA. Acute

and steady

- state assessments were conducted for food only, drinking water only, and for food and drinking water. W hen a drinking water only assessment resulted in a risk of concern at the

99.9 th 

### percentile

, a food and drinking water assessment was not conducted for that drinking water

scenario since the combined assessment would al so result in risks of concern at the 99.9 th


### percentile.

5.4.1 Overview of Residue Data Used

The residue chemistry database is a dequate to support current Registration Review requirements.

Both the acute and steady

- state assessments were refined using distributions and point estimates derived from PDP monitoring data, PCT data, empirical and default processing factors, and cooking factors derived from literature studies . If monitoring data were not available for a particular commodity (i.e., mung beans), but were available for a similar commodity (i.e., black

8 MRID 48041103

- Marin, J.E. 2010. Determination of the effect of chlorination on the degradation of dimethoate

in water.Dimethoate Human Health Risk Assessment DP No. D416010

Page 35 of 104 

### beans), the available data were translated to the similar crop. HED SOP 99.3, HED SOP 2000.1, and use pattern information were used as guidance for translations. When data were translated, the residue distribution file (RDF) was adjusted to account for differences in PCT. All RDFs were adjusted to account for the acute (8X) and steady

- state (3X) omethoate TAFs. Tolerance

level values were used for pecan, sorghum, safflower, and cottonseed since monitoring data were

not available for these commodities. HED previously recommended that tolerances for residues

of dimethoate an d omethoate in/on egg and poultry meat byproducts should be revoked ( M. Sahafeyan D232849; 24

- MAY

- 2011 ); however, the 40 CFR still includes tolerances for these commodities. Egg and poultry meat byproduct PDP data were included in the assessments as a

con servative assumption.

The most recent dietary memo ( J. Van Alstine; 15

- SEP

- 2015; D418590 ) summarizes the residue inputs (RDFs used, point estimates, processing and cooking factors, PCT, etc.), empirical processing factor calculations, residue data used f or each commodity, procedures for combining residues of dimethoate and omethoate, and all of the RDF files used for the acute and steady

state assessments.

5.4.2 Percent Crop Treated Used in Dietary Assessment

The acute and steady

- state analyses incorporated maximum PCT data provided by BEAD for the following commodities: alfalfa (<2.5%); a sparagus (5%); b eans, green (20%) ; b roccoli (55%);

c antaloupe s (10%); c auliflower (45%); c elery (35%); c herry (15%); c orn (<2.5%); c otton (<2.5%); d r y beans/peas (10%); g rapefruit (15%); l emon s ( 20%); l ettuce (35%); o range s (25%);

p ears (<2.5%); p eas, green (25%); p ecan (5%); p eppers (25%); p otatoes (15%); s orghum (<2.5%); s oybeans (<2.5%); t angerine s (5%); t omato es (40%); w atermelon s (10%); and w heat (<2.5%)

.

5.4.3 Acute Dietary Risk Assessment

The food only acute dietary risk estimates are summarized in Table 5.4.6.1 and are above HED’s LOC ( > 100% of the aPAD) for the U.S. population and all population subgroups at the 99.9 th


### percentile. T he U.S. p opulation was 270% of the aPAD and children 1

- 2 years old, the most highly exposed population subgroup , was 640% of the aPAD

. For the acute drinking water only runs, all (24) of the maximum application rate and 19 of the typical application rate drinking

water scenarios resulted in risks of concern at the 99.9 th 

### percentile.

Since the food alone and drinking water alone assessments result in risks of concern, acute food and drinking water analyses were not completed for all of the scenarios since they would also

result in risks of concern at the 99.9 th 

### percentile. Overall, a cute food and drinking water analyses

were conducted for the 27 ( 7 maximum application rate and 20 typical application rate) drinking

water scenarios and are summarized in Tables 5. 4.6.3 and 5.4.6.4 for the most highly exposed population subgroups. Infants and children 1

- 2 years old were the most highly exposed population subgroups for these scenarios, with risk estimates that ranged from 710

- 1100% of the

aPAD and 640

- 680 % of the aP AD at the 99.9 th 

### percentile, respectively. The results for all population subgroups (general U.S. p opulation, all infants (<1 year old), children 1

- 2, children 3

- 5, children 6

- 12, youth 13

- 19, females 13

- 49, adults 20

- 49, and adults 50

- 99 years) for all runs are summarized in the most recent dietary memo ( J. Van Alstine; 15

- SEP

- 2015; D418590 ).Dimethoate Human Health Risk Assessment DP No. D416010

Page 36 of 104 

### 5. 4.4 Steady

- State Dietary Risk Assessment

The food only steady

- state results are summarized in Table 5.4.6.2 and are above HED’s LOC ( > 100% of the ssPAD) for the U.S. population and all population subgroups at the 99.9 th


### percentile. T he U.S. population was 410% of the ssPAD and children 1

- 2 years old, the most highly exposed population subgroup , was 810% of the ssPAD

. For the steady

- state drinking water only ana lyses, all (24) of the maximum application rate and 19 of the typical application rate drinking water scenarios resulted in risks of concern at the 99.9 th 

### percentile.

Since the food alone and drinking water alone assessments result in risks of concern, steady

- state food and drinking water analyses were not completed for all of the scenarios since they would

also result in risks of concern at the 99.9 th 

### percentile. Overall, food and drinking water steady

state analyses were conducted for 23 drinking water scenarios (3 maximum application rate and 20 typical application rate) and are summarized in Tables 5.4.6.5 and 5.4.6.6 for the most highly exposed population subgr oups. Infants and children 1

- 2 years old were the most highly exposed population subgroups for these scenarios, with risk estimates that ranged from 970

- 1200 % of the

ss PAD and 810

- 880 % of the ss PAD at the 99.9 th 

### percentile, respectively. The results for all population subgroups (general U.S. p opulation, all infants (<1 year old), children 1

- 2, children 3

- 5, children 6

- 12, youth 13

- 19, females 13

- 49, adults 20

- 49, and adults 50

- 99 years) for all runs are summarized in the most recent dietary memo ( J. Van A lstine; 15

- SEP

- 2015; D418590 )

5.4.5 Cancer Dietary Risk Assessment

Dimethoate is classified as a Group C carcinogen (possible human carcinogen). Quantification of risk using a non

- linear approach will adequately account for all chronic toxicity, includi ng carcinogenicity that could result from exposure to dimethoate.Dimethoate Human Health Risk Assessment DP No. D416010

Page 37 of 104 

### 5.4.6. Dietary Assessment Summary Tables

Table 5.4.6.1 . Summary of Acute Dietary (Food Only) Exposure and Risk for Dimethoate and

Omethoate 1

.

Population Subgroup aPAD (mkd) 2 95 th Percentile 99 th Percentile 99.9 th Percentile

Exposure (mkd) %

aPAD Exposure

(mkd) %

aPAD Exposure

(mkd) %

aPAD
General U.S. Population

0.00091 0.000630 69 0.001192 130 0.002501 270 All Infants (<1 year old) 0.000933 100 0.001668 180 0.002506 280

Children 1

- 2 years old 0.001691 190 0.002912 320 0.005779 640

Children 3

- 5 years old 0.001267 140 0.002226 240 0.005053 560

Children 6

- 12 years old 0.000762 84 0.001394 150 0.002811 310

Youth 13

- 19 years old 0.000452 50 0.000929 100 0.001683 180

Adults 20

- 49 years old 0.000391 43 0.000735 81 0.001447 160

Adults 50

- 99 years old 0.000370 4.1 0.000652 7.2 0.001346 15

Females 13

- 49 years old 0.000380 42 0.000758 83 0.001399 150

Residue file: Dimethoate Acute File December 19 2014__FOOD ONLY.R08; Residue file dated: 12

- 19

- 2014/16:47:51

1 Population with the greatest exposure is in bold. The exposure assessment was run using a rounded aPAD value of 0.009 mkd. The %aPAD values have been updated to reflect the unrounded aPAD value and have been rounded to two significant figures.

2 mkd = mg/kg/day. Includes 10x FQPA SF for all population subgroups except adults 50

- 99 years old. The aPAD

for adults 50

- 99 years old is 0.0091 mkd.

Table 5.4.6.2 . Summary of Steady

- State (Two

- Day Average) Dietary (Food Only) Exposure and Risk for

Di methoate and Omethoate 1

.

Population Subgroup ss PAD (mkd) 2 95 th Percentile 99 th Percentile 99.9 th Percentile

Exposure (mkd) %

ss PAD Exposure

(mkd) %

ss PAD Exposure

(mkd) %

ss PAD
General U.S. Population

0.00022 0.000276 130 0.000493 220 0.000909 410 All Infants (<1 year old) 0.000410 190 0.000670 300 0.000974 440

Children 1

- 2 years old 0.000706 320 0.001022 460 0.001775 810

Children 3

- 5 years old 0.000516 230 0.000772 350 0.001465 670

Children 6

- 12 years old 0.000331 150 0.000496 230 0.000964 440

Youth 13

- 19 years old 0.000196 89 0.000302 140 0.000508 230

Adults 20

- 49 years old 0.000159 72 0.000255 120 0.000475 220

Adults 50

- 99 years old 0.000145 6.6 0.000231 11 0.000435 20

Females 13

- 49 years old 0.000158 72 0.000259 120 0.000458 210

Residue file: Dimethoate Steady

- state File December 30 2014__FOOD ONLY_ssRfD.R08; Residue file dated: 12

- 30

- 2014/10:45:39

1 Population with the greatest exposure is in bold. The exposure assessment was run using the rounded ssPAD value of 0.002 mkd. The %ssPAD values have been updated to reflect the unrounded ssPAD value and have been rounded to two significant figures.

2 mk d = mg/kg/day. Includes 10x FQPA SF for all population subgroups except adults 50

- 99 years old. The ssPAD

for adults 50

- 99 years old is 0.0022 mkd.Dimethoate Human Health Risk Assessment DP No. D416010

Page 38 of 104 Table 5.4.6.3 . Summary of Acute Assessment Results for Maximum Application Rate Drinking Water Scenarios (Water Only: 95th and 99.9th Per centiles; Food+Water: 99.9th Percentile). (Values <100% aPAD are Shaded and in Bold.)

Drinking Water Scenario (bold font)/ Crops/Uses Represented Acute WATER ONLY (All Infants <1 year old) Acute WATER ONLY (Children 1

- 2 years old) Acute FOOD and WATER Highest Exposure

Estimate

95 th 99.9 th 95 th 99.9 th
Population Subgroup 99.9 th
Exposure (mkd) %

aPAD Exposure

(mkd) %

aPAD Exposure

(mkd) %

aPAD Exposure

(mkd) %

aPAD Exposure (mkd) %

aPAD
01_CA wine grapes/ Agricultural uncultivated areas (CA only) (Noncropland adjacent to vineyards) 0.00313 0 340 0.047486 5200 0.001596 180 0.023139 2500 N/C N/C N/C

03_MN alfalfa/ Alfalfa, Sainfoin 0.00226 0 250 0.012488 1400 0.001083 120 0.006579 720 N/C N/C N/C

04_CA cole crops/ Broccoli, Cauliflower; Additionally, Brussels sprouts (aerial, some labels allow use only in CA) 0.004635 510 0.028422 3100 0.002352 260 0.015074 1700 N/C N/C N/C

06_CA row crops/ Celery 0.001555 170 0.008732 960 0.00076 0 84 0.004674 510 All Infants (<1 year old) 0.008981 990

07_FL cabbage/ Turnip (greens) 0.002608 290 0.016004 1800 0.001328 150 0.008751 960 N/C N/C N/C

08_CA potato/ Turnip (roots) 0.00233 0 260 0.012046 1300 0.001178 130 0.006658 730 N/C N/C N/C

09_WA orchards/ Cherry (only in ID, MT, OR, UT and WA) 0.002461 270 0.009575 1100 0.001173 130 0.005499 600 All Infants (<1 year old) 0.009749 1100

10_WA orchards/ Cherry (only in ID, MT, OR, UT and WA) 0.002797 310 0.009974 1100 0.001303 140 0.005854 640 All Infants (<1 year old) 0.010227 1100

12_OR Xmas trees/ Douglas fir (seed orchards) (only in OR and WA) 0.002453 270 0.013023 1400 0.001266 140 0.007147 790 N/C N/C N/C

13_CA forestry/ Cottonwood (forest/ shelterbelt) 0.009973 1100 0.036147 4000 0.004655 510 0.021136 2300 N/C N/C N/CDimethoate Human Health Risk Assessment DP No. D416010

Page 39 of 104 Table 5.4.6.3 . Summary of Acute Assessment Results for Maximum Application Rate Drinking Water Scenarios (Water Only: 95th and 99.9th Per centiles; Food+Water: 99.9th Percentile). (Values <100% aPAD are Shaded and in Bold.)

Drinking Water Scenario (bold font)/ Crops/Uses Represented Acute WATER ONLY (All Infants <1 year old) Acute WATER ONLY (Children 1

- 2 years old) Acute FOOD and WATER Highest Exposure

Estimate

95 th 99.9 th 95 th 99.9 th
Population Subgroup 99.9 th
Exposure (mkd) %

aPAD Exposure

(mkd) %

aPAD Exposure

(mkd) %

aPAD Exposure

(mkd) %

aPAD Exposure (mkd) %

aPAD 18_NJ nursery/

Ornamental herbaceous plants 1 0.007523 830 0.096285 11000 0.004324 480 0.048787 5400 N/C N/C N/C

20_FL peppers/ Peppers 0.002748 300 0.034351 3800 0.0015 00 160 0.017 000 1900 N/C N/C N/C

21_FL peppers/ Peppers 0.002044 220 0.033765 3700 0.001176 130 0.016433 1800 N/C N/C N/C

22_MI beans / Beans (includes dry beans, excludes cowpeas), Garbanzos (includes chick peas), Lupine 0.001478 160 0.009937 1100 0.000744 82 0.005244 580 All Infants (<1 year old) 0.010354 1100

24_PA Tomato /

Tomato 0.001825 200 0.032938 3600 0.000936 100 0.015693 1700 N/C N/C N/C

25_CA citrus / Grapefruit, Kumquat, Lemon, Lime, Orange, Pummelo (shaddock), Tangelo, Tangerine 0.000889 98 0.006597 720 0.000513 56 0.003575 390 All Infants (<1 year old) 0.006881 760

26_FL citrus / Same crops as above 0.001208 130 0.02569 0 2800 0.000759 83 0.012608 1400 N/C N/C N/C

27_ID potatoes /

Potatoes 0.00314 0 350 0.015391 1700 0.001564 170 0.008542 940 N/C N/C N/C

05_CA cole crops/ Brussels sprouts (ground) 0.003661 400 0.044642 4900 0.002022 220 0.022424 2500 N/C N/C N/C

14_OR Xmas trees/ Hybrid cottonwood/poplar plantations (some labels allow use in ID, OR and WA) 0.009177 1000 0.037244 4100 0.004391 480 0.021056 2300 N/C N/C N/CDimethoate Human Health Risk Assessment DP No. D416010

Page 40 of 104 Table 5.4.6.3 . Summary of Acute Assessment Results for Maximum Application Rate Drinking Water Scenarios (Water Only: 95th and 99.9th Per centiles; Food+Water: 99.9th Percentile). (Values <100% aPAD are Shaded and in Bold.)

Drinking Water Scenario (bold font)/ Crops/Uses Represented Acute WATER ONLY (All Infants <1 year old) Acute WATER ONLY (Children 1

- 2 years old) Acute FOOD and WATER Highest Exposure

Estimate

95 th 99.9 th 95 th 99.9 th
Population Subgroup 99.9 th
Exposure (mkd) %

aPAD Exposure

(mkd) %

aPAD Exposure

(mkd) %

aPAD Exposure

(mkd) %

aPAD Exposure (mkd) %

aPAD
10b_WA orchards/ Cherry (only in ID, MT, OR, UT and WA) 0.001378 150 0.004921 540 0.000642 71 0.002894 320 Children 1

- 2 years old 0.006152 680

15_CA nursery/ Citrus, non

- bearing and nursery stock (only in CA and AZ) 0.001228 130 0.006874 760 0.000645 71 0.00378 420 All Infants (<1 year old) 0.007164 790

23_MS Cotton /

Cotton 0.001079 120 0.012753 1400 0.000601 66 0.006364 700 N/C N/C N/C

17_OR nursery/ Ornamental woody shrubs and vines;

Ornamental and/or

shade trees 0.005901 650 0.023714 2600 0.002798 310 0.013584 1500 N/C N/C N/C

Bold and shaded values are < 100% of the aPAD. N/C = not calculated. Since the food alone and drinking water alone assessments result in risks of concer n, acute food and drinking water analyses were not completed for the majority of the scenarios since they would also result in risk s of concern at the 99.9th percentile. Food and drinking water exposure assessments were conducted for a subset of drinking water scenarios as an example of the combined dietary exposures and risks even though food alone and water alone resulted in risks of concern. The exposure assessments were run using a rounded aPAD value of 0.009 mkd. The %aPAD values have been updated to reflect the unrounded aPAD value of 0.00091 m kd and were adjusted to two significant figures. The results for all population sub groups (general U.S. population, all infants (<1 year old), children 1

- 2, children 3

- 5, children 6

- 12, youth 13

- 19, females 13

- 49, adults 20

- 49, and adults 50

- 99 years) for all runs are summarized in the most recent dietary memo ( J. Van Alstine; 15

- SEP

- 201 5; D418590 ).

1 A maximum rate of 6.5 lb ai/A for this use appears to be a label error; therefore, these results are not considered represent ative. A drinking water only assessment was completed using this distributions since the label has not yet been modified.

Tabl e 5.4.6.4 . Summary of Acute Assessment Results for Typical Application Rate Drinking Water Scenarios (Water Only: 95th and 99.9th Per centiles; Food+Water: 99.9th Percentile). (Values <100% aPAD are Shaded and in Bold.)

Drinking Water Scenario (bold font)/ Crops/Uses Represented Acute WATER ONLY (All Infants <1 year old) Acute WATER ONLY (Children 1

- 2 years old) Acute FOOD and WATER Highest Exposure

Estimate

95 th 99.9 th 95 th 99.9 th
Population Subgroup 99.9 th
Exposure (mkd) %

aPAD Exposure

(mkd) %

aPAD Exposure

(mkd) %

aPAD Exposure

(mkd) %

aPAD Exposure (mkd) %

aPAD

03c_MN alfalfa/ Alfalfa 0.000444 49 0.003749 410 0.000231 25 0.001913 210 Children 1

- 2 years old 0.005846 640 04b_CA cole crops/

Broccoli 0.000773 85 0.00792 0 870 0.000409 45 0.004006 440 All Infants (<1 year old) 0.008169 900Dimethoate Human Health Risk Assessment DP No. D416010

Page 41 of 104 Tabl e 5.4.6.4 . Summary of Acute Assessment Results for Typical Application Rate Drinking Water Scenarios (Water Only: 95th and 99.9th Per centiles; Food+Water: 99.9th Percentile). (Values <100% aPAD are Shaded and in Bold.)

Drinking Water Scenario (bold font)/ Crops/Uses Represented Acute WATER ONLY (All Infants <1 year old) Acute WATER ONLY (Children 1

- 2 years old) Acute FOOD and WATER Highest Exposure

Estimate

95 th 99.9 th 95 th 99.9 th
Population Subgroup 99.9 th
Exposure (mkd) %

aPAD Exposure

(mkd) %

aPAD Exposure

(mkd) %

aPAD Exposure

(mkd) %

aPAD Exposure (mkd) %

aPAD 17b_OR nursery/ Ornamental woody shrubs and vines; Ornamental

and/or shade trees 0.000368 40 0.002475 270 0.000194 21 0.001305 140 Children 1

- 2 years old 0.005798 640

18b_NJ nursery/

Ornamental herbaceous plants 0.000281 31 0.003593 390 0.000161 18 0.00182 0 200 Children 1

- 2 years old 0.005836 640

22c _MI beans / Dry beans,

peas 0.00035 0 38 0.004195 460 0.000194 21 0.002109 230 Children 1

- 2 years old 0.005875 650

23c_MS Cotton / Cotton 0.000171 19 0.003917 430 0.000109 12 0.001907 210 Children 1

- 2 years old 0.005835 640
24b_PA Tomato / Tomato 0.000187 21 0.002325 260 0.000098 11 0.001128 120 Children 1

- 2 years old 0.005831 640
26b_FL citrus / Oranges 0.000226 25 0.005462 600 0.000141 15 0.002659 290 Children 1

- 2 years old 0.005987 660

27c_ID potatoes / Potatoes 0.001333 150 0.006605 730 0.000665 73 0.003655 400 All Infants (<1 year old) 0.006905 760

27d_ID potatoes / Potatoes 0.000629 69 0.003762 410 0.000328 36 0.002042 220 Children 1

- 2 years old 0.005869 640

28_IL corn / Corn 0.000451 50 0.007578 830 0.000243 27 0.003537 390 All Infants (<1 year old) 0.007916 870

29_KS sorghum

/ Sorghum 0.000267 29 0.006286 690 0.000151 17 0.003154 350 All Infants (<1 year old) 0.006488 710

30_MS soybeans / Soybeans 0.000282 31 0.003531 390 0.000167 18 0.001744 190 Children 1

- 2 years old 0.00584 640

31_OR snap beans / Lima

beans 0.000547 60 0.002682 290 0.000272 30 0.001503 170 Children 1

- 2 years old 0.005807 640

32_ND wheat / Spring

wheat 0.000205 23 0.001274 140 0.000112 12 0.0007 00 77 Children 1

- 2 years old 0.005815 640

33_ND wheat / Winter

wheat 0.000255 28 0.001587 170 0.000139 15 0.000872 96 Children 1

- 2 years old 0.005788 640

13b_CA forestry/ Cottonwood (forest/ shelterbelt) 0.001209 130 0.006982 770 0.00061 0 67 0.003794 420 All Infants (<1 year old) 0.00737 0 810

14b_OR Xmas trees/ Hybrid cottonwood/poplar 0.001083 120 0.005602 620 0.000558 61 0.003099 340 Children 1

- 2 years old 0.006109 670Dimethoate Human Health Risk Assessment DP No. D416010

Page 42 of 104 Tabl e 5.4.6.4 . Summary of Acute Assessment Results for Typical Application Rate Drinking Water Scenarios (Water Only: 95th and 99.9th Per centiles; Food+Water: 99.9th Percentile). (Values <100% aPAD are Shaded and in Bold.)

Drinking Water Scenario (bold font)/ Crops/Uses Represented Acute WATER ONLY (All Infants <1 year old) Acute WATER ONLY (Children 1

- 2 years old) Acute FOOD and WATER Highest Exposure

Estimate

95 th 99.9 th 95 th 99.9 th
Population Subgroup 99.9 th
Exposure (mkd) %

aPAD Exposure

(mkd) %

aPAD Exposure

(mkd) %

aPAD Exposure

(mkd) %

aPAD Exposure (mkd) %

aPAD plantations (some labels allow use in ID, OR and WA) 15b_CA nursery/ Citrus,

non

- bearing and nursery stock (only in CA and AZ) 0.000108 12 0.000604 66 0.000057 6 .3 0.000332 36 Children 1

- 2 years old 0.00578 640

12b_OR Xmas trees/ Douglas fir (seed orchards) (only in OR and WA) 0.000546 60 0.002896 320 0.000282 31 0.00159 170 Children 1

- 2 years old 0.005807 640

Bold and shaded values are <100% of the aPAD. N/C = n ot c alculated. The exposure assessment s w ere run using a rounded aPAD value of 0.009 mkd. The %aPAD values have been updated to reflect the unrounded aPAD value of 0.0 0 091 mkd and were adjusted to two significant figures

. The results for all population subgroups (general U.S. p opulation, all infants (<1 year old), children 1

- 2, children 3

- 5, children 6

- 12, youth 13

- 19, females 13

- 49, adults 20

- 49, and adults 50

- 99 years) for all runs are summarized in the most recent dietary memo ( J. Van Alstine; 15

- SEP

- 2015; D418590 ).

Table 5. 4.6.5 . Summary of Steady

- State ( Two

- Day Average ) Assessment Results for Maximum Application Rate Drinking Water Scenarios (Water Only: 95th and 99.9th Percentiles; Food+Water: 99.9th Percentile). (Values <100% ssPAD are Shaded and in Bold.)

Drinking Water Scenario (bold font)/ Crops/Uses Represented Two

- Day Average WATER ONLY (All Infants <1 year old) Two

- Day Average WATER ONLY (Children 1

- 2 years old) Two

- Day Average FOOD and WATER Highest Exposure Estimate

95 th 99.9 th 95 th 99.9 th Population Subgroup 99.9 th

Exposure (mkd) %

ssPAD Exposure

(mkd) %

ssPAD Exposure

(mkd) %

ssPAD Exposure

(mkd) %

ssPAD Exposure (mkd) %

ssPAD
01_CA wine grapes/ Agricultural uncultivated areas (CA only) (Noncropland adjacent to vineyards) 0.001087 490 0.0161 00 7300 0.000562 260 0.007729 3500 N/C N/C N/C

03_MN alfalfa/ Alfalfa,

Sainfoin 0.000818 370 0.004016 1800 0.000392 180 0.002055 930 N/C N/C N/C

04_CA cole crops/ Broccoli, Cauliflower; Additionally, Brussels sprouts (aerial, some 0.00173 0 790 0.009069 4100 0.000872 400 0.004692 2100 N/C N/C N/CDimethoate Human Health Risk Assessment DP No. D416010

Page 43 of 104 Table 5. 4.6.5 . Summary of Steady

- State ( Two

- Day Average ) Assessment Results for Maximum Application Rate Drinking Water Scenarios (Water Only: 95th and 99.9th Percentiles; Food+Water: 99.9th Percentile). (Values <100% ssPAD are Shaded and in Bold.)

Drinking Water Scenario (bold font)/ Crops/Uses Represented Two

- Day Average WATER ONLY (All Infants <1 year old) Two

- Day Average WATER ONLY (Children 1

- 2 years old) Two

- Day Average FOOD and WATER Highest Exposure Estimate

95 th 99.9 th 95 th 99.9 th Population Subgroup 99.9 th

Exposure (mkd) %

ssPAD Exposure

(mkd) %

ssPAD Exposure

(mkd) %

ssPAD Exposure

(mkd) %

ssPAD Exposure (mkd) %

ssPAD labels allow use only in CA) 06_CA row crops/ Celery 0.00057 0 260 0.002854 1300 0.000279 130 0.001469 670 N/C N/C N/C

07_FL cabbage/ Turnip (greens) 0.000976 440 0.005096 2300 0.000501 230 0.002641 1200 N/C N/C N/C

08_CA potato/ Turnip (roots) 0.000871 400 0.003973 1800 0.000432 200 0.002099 950 N/C N/C N/C

09_WA orchards/ Cherry (only in ID, MT, OR, UT and WA) 0.000888 400 0.002903 1300 0.000415 190 0.001652 750 N/C N/C N/C

10_WA orchards/ Cherry (only in ID, MT, OR, UT and WA) 0.000993 450 0.003111 1400 0.000465 210 0.001773 810 N/C N/C N/C

12_OR Xmas trees/ Douglas fir (seed orchards) (only in OR and WA) 0.00094 0 430 0.003944 1800 0.000456 210 0.002166 980 N/C N/C N/C

13_CA forestry/ Cottonwood (forest/ shelterbelt) 0.003578 1600 0.011923 5400 0.001671 760 0.006713 3100 N/C N/C N/C

18_NJ nursery/

Ornamental herbaceous plants 1 0.003069 1400 0.029122 13000 0.001702 770 0.014279 6500 N/C N/C N/C

20_FL peppers/ Peppers 0.00111 0 500 0.010331 4700 0.000591 270 0.005063 2300 N/C N/C N/C

21_FL peppers/ Peppers 0.000859 390 0.010034 4600 0.000478 220 0.004894 2200 N/C N/C N/C

22_MI beans / Beans (includes dry beans, excludes cowpeas), Garbanzos (includes chick peas), Lupine 0.000545 250 0.003227 1500 0.000276 130 0.001625 740 N/C N/C N/CDimethoate Human Health Risk Assessment DP No. D416010

Page 44 of 104 Table 5. 4.6.5 . Summary of Steady

- State ( Two

- Day Average ) Assessment Results for Maximum Application Rate Drinking Water Scenarios (Water Only: 95th and 99.9th Percentiles; Food+Water: 99.9th Percentile). (Values <100% ssPAD are Shaded and in Bold.)

Drinking Water Scenario (bold font)/ Crops/Uses Represented Two

- Day Average WATER ONLY (All Infants <1 year old) Two

- Day Average WATER ONLY (Children 1

- 2 years old) Two

- Day Average FOOD and WATER Highest Exposure Estimate

95 th 99.9 th 95 th 99.9 th Population Subgroup 99.9 th

Exposure (mkd) %

ssPAD Exposure

(mkd) %

ssPAD Exposure

(mkd) %

ssPAD Exposure

(mkd) %

ssPAD Exposure (mkd) %

ssPAD
24_PA Tomato / Tomato 0.000675 310 0.011389 5200 0.000348 160 0.005484 2500 N/C N/C N/C
25_CA citrus / Grapefruit, Kumquat, Lemon, Lime, Orange, Pummelo (shaddock), Tangelo, Tangerine 0.000381 170 0.001826 830 0.000194 88 0.000975 440 Children 1

- 2 years old 0.001929 880

26_FL citrus / Same crops as above 0.000551 250 0.00794 0 3600 0.000307 140 0.003761 1700 N/C N/C N/C

27_ID potatoes /

Potatoes 0.001161 530 0.004764 2200 0.000568 260 0.002548 1200 N/C N/C N/C

05_CA cole crops/ Brussels sprouts (ground) 0.001412 640 0.014579 6600 0.000776 350 0.0072 00 3300 N/C N/C N/C

14_OR Xmas trees/ Hybrid cottonwood/poplar plantations (some labels allow use in ID, OR and WA) 0.00332 0 1500 0.011918 5400 0.001574 720 0.006844 3100 N/C N/C N/C

10b_WA orchards/ Cherry (only in ID, MT, OR, UT and WA) 0.000489 220 0.001542 700 0.000229 100 0.000877 400 Children 1

- 2 years old 0.001913 870

15_CA nursery/ Citrus,

non

- bearing and nursery stock (only in CA and AZ) 0.000481 220 0.001987 900 0.000235 110 0.001081 490 All Infants (<1 year old) 0.002124 970

23_MS Cotton / Cotton 0.000433 200 0.004079 1900 0.000234 110 0.002005 910 N/C N/C N/C 17_OR nursery/ Ornamental woody shrubs and vines;

Ornamental and/or shade

trees 0.002123 970 0.007785 3500 0.001009 460 0.004241 1900 N/C N/C N/CDimethoate Human Health Risk Assessment DP No. D416010

Page 45 of 104 Bold and shaded values are <100% of the ss PAD. N/C = n ot c alculated. Since the food alone and drinking water alone assessments result in risks of concern, steady

- state (two

day average) food and drinking water analyses were not com pleted for the majority of the scenarios since they would also result in risks of concern at the 99.9th percentile. Food and drinking water exposure assessments were conducted for a subset of drinking water scenarios as an example of the combined dietary exposures and risks even though food

alone and water alone resulted in risks of concern. The exposure assessment s w ere run using a rounded ss PAD value of 0.00 2 mkd. The % ss PAD values have been updated to

reflect the unrounded ss PAD value of 0.00 022 mkd and were adjusted to two significant figures

. The results for all popu lation subgroups (general U.S. p opulation, all infants (<1 year old), children 1

- 2, children 3

- 5, childr en 6

- 12, youth 13

- 19, females 13

- 49, adults 20

- 49, and adults 50

- 99 years) for all runs are summarized in the most recent dietary memo ( J. Van Alstine; 15

- SEP

- 2015; D418590 ).

Table 5.4.6.6 . Summary of Steady

- State ( Two

- Day Average ) Assessment Results for Typical Application Rate Drinking Water Scenarios (Water Only: 95th and 99.9th Percentiles; Food+Water: 99.9th Percentile). (Values <100% ssPAD are Shaded and in Bold.)

Drinking Water Scenario (bold font)/ Crops/Uses Represented Two

- Day Average WATER ONLY (All Infants <1 year old) Two

- Day Average WATER ONLY (Children 1

- 2 years old) Two

- Day Average FOOD and WATER Highest Exposure Estimate

95 th 99.9 th 95 th 99.9 th
Population Subgroup 99.9 th

Exposure (mkd) %

ssPAD Exposure

(mkd) %

ssPAD Exposure

(mkd) %

ssPAD Exposure

(mkd) %

ssPAD Exposure (mkd) %

ssPAD

03c_MN alfalfa/

Alfalfa 0.00017 0 77 0.00122 0 550 0.000085 39 0.000591 270 Children 1

- 2 years

old 0.001802 820

04b_CA cole crops/

Broccoli 0.000291 130 0.002549 1200 0.000153 70 0.001241 560 All Infants (<1 year old) 0.002687 1200

17b_OR nursery/ Ornamental woody shrubs and vines;

Ornamental and/or

shade trees 0.000142 65 0.000761 350 0.000071 32 0.000396 180 Children 1

- 2 years

old 0.001792 810

18b_NJ nursery/

Ornamental herbaceous plants 0.000114 52 0.001087 490 0.000064 29 0.000533 240 Children 1

- 2 years

old 0.001792 810

22c _MI beans / Dry beans, peas 0.000141 64 0.001328 600 0.000074 34 0.00064 290 Children 1

- 2 years

old 0.001805 820

23c_MS Cotton /

Cotton 0.000081 37 0.00117 530 0.000046 21 0.000566 260 Children 1

- 2 years

old 0.00179 0 810

24b_PA Tomato /

Tomato 0.000071 32 0.000787 360 0.000036 16 0.000385 180 Children 1

- 2 years

old 0.001789 810

26b_FL citrus / Oranges 0.000101 46 0.001687 770 0.000057 26 0.000797 360 Children 1

- 2 years

old 0.001821 830

27c_ID potatoes /

Potatoes 0.000494 220 0.00205 0 930 0.000242 110 0.001092 500 All Infants (<1 year old) 0.002183 990

27d_ID potatoes /

Potatoes 0.000244 110 0.001088 490 0.000121 55 0.000571 260 Children 1

- 2 years

old 0.00181 0 820Dimethoate Human Health Risk Assessment DP No. D416010

Page 46 of 104 Table 5.4.6.6 . Summary of Steady

- State ( Two

- Day Average ) Assessment Results for Typical Application Rate Drinking Water Scenarios (Water Only: 95th and 99.9th Percentiles; Food+Water: 99.9th Percentile). (Values <100% ssPAD are Shaded and in Bold.)

Drinking Water Scenario (bold font)/ Crops/Uses Represented Two

- Day Average WATER ONLY (All Infants <1 year old) Two

- Day Average WATER ONLY (Children 1

- 2 years old) Two

- Day Average FOOD and WATER Highest Exposure Estimate

95 th 99.9 th 95 th 99.9 th
Population Subgroup 99.9 th

Exposure (mkd) %

ssPAD Exposure

(mkd) %

ssPAD Exposure

(mkd) %

ssPAD Exposure

(mkd) %

ssPAD Exposure (mkd) %

ssPAD

28_IL corn / Corn 0.000169 77 0.002382 1100 0.000092 42 0.001147 520 All Infants (<1 year old) 0.00248 0 1100

29_KS sorghum

/ Sorghum 0.000108 49 0.002212 1000 0.000058 26 0.001033 470 All Infants (<1 year old) 0.002362 1100

30_MS soybeans / Soybeans 0.000122 55 0.00103 470 0.000066 30 0.000517 240 Children 1

- 2 years

old 0.001793 820

31_OR snap beans /

Lima beans 0.000202 92 0.000825 380 0.000099 45 0.000458 210 Children 1

- 2 years

old 0.001794 820

32_ND wheat / Spring

wheat 0.000082 37 0.000381 170 0.000041 19 0.000202 92 Children 1

- 2 years

old 0.001786 810

33_ND wheat /

Winter wheat 0.000102 46 0.000474 220 0.000051 23 0.000252 110 Children 1

- 2 years

old 0.001787 810

13b_CA forestry/ Cottonwood (forest/ shelterbelt) 0.000455 210 0.002198 1000 0.000219 100 0.001155 530 All Infants (<1 year old) 0.002338 1100

14b_OR Xmas trees/ Hybrid cottonwood/poplar plantations (some labels allow use in ID, OR and WA) 0.000415 190 0.001671 760 0.000201 91 0.000912 410 Children 1

- 2 years old 0.001909 870

15b_CA nursery/ Citrus, non

- bearing and nursery stock (only in CA and AZ) 0.000042 19 0.000175 80 0.000021 10 0.000095 43 Children 1

- 2 years

old 0.001777 810

12b_OR Xmas trees/ Douglas fir (seed orchards) (only in OR and WA) 0.000209 95 0.000877 400 0.000101 46 0.000482 220 Children 1

- 2 years

old 0.001796 820

Bold and shaded values are ≤100% of the ss PAD. The exposure assessments were run using a rounded ssPAD value of 0.002 mkd. The %ssPAD values have been updated to reflect the unrounded ssPAD value of 0.00022 mkd and were adjusted to two significant figures. The results for all population subgroups (general U .S. population, all infants (<1 year old), children 1

- 2, children 3

- 5,

children 6

- 12, youth 13

- 19, females 13

- 49, adults 20

- 49, and adults 50

- 99 years) for all runs are summarized in the most recent dietary memo ( J. Van Alstine; 15

- SEP

- 2015; D418590 ).Dimethoate Human Health Risk Assessment DP No. D416010

Page 47 of 104 

### 6.0 Residential (Non

- Occupational) Exposure/Risk Characterization

All residential and other non

- occupational uses of dimethoate were voluntarily cancelled, effective March 13, 2002

. 9 

### Currently, dimethoate is registered solely for use on occupational

sites.

6.1 Residential Handler Exposure

HED uses the term “handlers” to describe those individuals who are involved in the pesticide application p rocess. There are currently no registered or proposed residential uses for

dimethoate ; therefore, a residential handler assessment was not performed.

6.2 Post

- Application Exposure

There are currently no registered or proposed residential uses for dimet hoate

. The potential for

non

- occupational post

- application exposure from agricultural applications of dimethoate has

been assessed below in Section 8.0

.

7.0 Non

- Occupational Bystander Post

- Application Inhalation Exposure and Risk

Estimates

Volatilization of pesticides may be a source of post

- application inhalation exposure to

individuals nearb y pesticide applications. The A gency sought expert advice and input on issues related to volatilization of pesticides from its FIFRA SAP in December 2 009, and received the SAP’s final report on March 2, 2010

. 10 

### The A gency has evaluated the SAP report and has developed a Volatilization Screening Tool and a subsequent Volatilization Screening Analysis

. 11



### D uring Registration Review, the A gency will utilize this analysis to determ ine if data (i.e., flux studies) or further analyse s are required for dimethoate

.

8.0 Non

- Occupational Spray Drift Exposure and Risk Estimates

Off

- target movement of pesticides can occur via many types of pathways and it is govern ed by a variety of factors. Sprays that are released and do not deposit in the application area end up off

target and can lead to exposures to those it may directly contact. They can also deposit on surfaces where contact with residues can eventually lea d to indirect exposures ( e.g

. , children playing on lawns where residues have deposited next to treated fields). The potential risk estimates from these residues can be calculated using drift modeling onto 50

- feet

- wide lawns coupled with methods employed for residential risk assessments for turf products.

The approach to be used for quantitatively incorporating spray drift into risk assessment is based on a premise of compliant applications that , by definition, should not result in direct exposures to

ind ividuals because of existing label language and other regulatory requirements intended to prevent them. 12 

### Direct exposures would include inhalation of the spray plume or being sprayed directly. Rather, the exposures addressed here are thought to occur ind irectly through contact

9 Federal Register Notice/Vol. 67, No. 84/Wednesday, May 01, 2002/Not ices/21669

10 http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html

11 http://www.regulations.gov/#!docketDetail;D=EPA

- HQ

- OPP

- 2014

- 0219

12 This approach is consistent with the requirements of the EPA’s Worker Protection Standard.Dimethoate Human Health Risk Assessment DP No. D416010

Page 48 of 104 

### with impacted areas, such as residential lawns, when compliant applications are conducted. Given this premise, exposures for children (1 to 2 years old) and adults who have contact with turf where residues are assumed to have depos ited via spray drift thus resulting in an indirect exposure are the focus of this analysis analogous to how exposures to turf products are

considered in risk assessment.

In order to evaluate the drift potential and associated risks, an approach based on drift modeling coupled with techniques used to evaluate residential uses of pesticides was utilized. Essentially, a residential turf assessment based on exposure to deposited residues has been completed to address drift from the agricultural applications of dimethoate. In the spray drift scenario, the deposited residue value was determined based on the amount of spray drift that may occur at varying distances from the edge of the treated field using the AgDrift ® 

### (v2.1.1) model and the Residential Exposur e Assessment Standard Operating Procedures Addenda 1: Consideration of Spray Drift Policy

. Once the deposited residue values were determined, the remainder of the spray drift assessment was based on the algorithms and input values specified in the recentl y revised (2012) Standard Operating Procedures For Residential Risk Assessment (SOPs)

.

For dimethoate, chemical

- specific turf transferrable residue ( TTR ) data are not available, therefore, the estimated TTR are based on a default assumption from the 2012 Residential SOPs that the transferable residue available for exposure is 1% of the total deposited residue, which is assumed to be equivalent to the maximum application rate. In order to account for the formation of the metabolite, omethoate, an assumpti on was made that 5% of the dimethoate residues would metabolize to omethoate. This assumption is based on a review of available TTR and DFR data for other OPs where both the parent and metabolite were measured in residue samples. Five percent was found t o be the high

- end value for the percent of parent that metabolized during the

course of the residue studies. Once the estimated omethoate residues were calculated (dimethoate residues x 5%), the resulting values were adjusted further by the steady

- state T AF value of 3 to account for the increased potency of omethoate since a dimethoate

- specific dermal toxicity study was used for calculation of the risk estimates.

A screening approach was developed based on the use of the AgDrift ® 

### model in situations whe re specific label guidance that defines application parameters is not available. 13 

### AgDrift ® 

### is appropriate for use only when applications are made by aircraft, airblast orchard sprayers, and groundboom sprayers. When AgDrift ® 

### was developed, a series of sc reening values (i.e., the Tier 1 option) were incorporated into the model and represent each equipment type and use under varied conditions. The screening options specifically recommended in this methodology were selected because they are plausible and re present a reasonable upper bound level of drift for common application methods in agriculture. These screening options are consistent with how spray drift is considered in a number of ecological risk assessments and in the process used to develop drinking water concentrations used for risk assessment. In all cases, each scenario is to be evaluated unless it is not plausible based on the anticipated use pattern (e.g., herbicides are not typically applied to tree canopies) or specific label prohibitions (e. g., aerial applications are not allowed). Section 8 .1 provides the screening

- level drift

- related risk estimates. In many cases, risks are of concern when the screening

- level estimates for spray drift are used as the basis for the analysis. In order to account for this issue and to provide additional risk management

13 http://www.agdrift .com/Dimethoate Human Health Risk Assessment DP No. D416010

Page 49 of 10 4 

### options

, additional spray drift deposition fractions were also considered. These drift estimates

represen t plausible options for pesticide labels.

8 .1 Combined Risk Estimates from Lawn Deposition Adjacent to Applications

The spray drift risk estimates are based on an estimated deposited residue concentration as a result of the screening level agricultural application scenarios. Dimethoate is registered on

various agricultural crops, Christmas tree farms, trees grown for pulp, and ornamentals in

outdoor nurseries . Most of the registered products are applied either via aerial, chemigation, groundboom, airbl ast or with handheld equipment. For most use sites, the maximum application rate is 2 lb ai/A, but for ornamentals in outdoor nurseries, the maximum application rate is 4.15 lb ai/A for airblast applications specifically. The recommended drift scenario s creening level options are listed below:

 Groundboom applications are based on the AgDrift ® 

### option for high boom height and using very fine to fine spray type using the 90 th 

### percentile results.

 Orchard airblast applications are based on the AgDrift ® 

### opti on for sparse (young/dormant) tree canopies.

 Aerial applications are based on the use of AgDrift ® 

### Tier 1 aerial option for a fine to medium spray type and a series of other parameters that will be described in more detail below (e.g., wind vector assumed t o be 10 mph in a downwind direction for entire application/drift event). 14



### In addition to the screening

- level spray

- drift scenarios described above, additional results are provided which represent viable drift

- reduction options that represent potential risk

- management options

. In particular, different spray qualities have been considered as well as the impact of other application conditions (e.g., boom height, use of a helicopter instead of fixed

- wing aircraft, crop canopy conditions).

Dermal risk estimates were calculated for adults

. For adults, when an endpoint is not sex

specific (i.e., the endpoints are based on developmental or fetal effects) a body weight of 80 kg is typically used in risk assessment; however, in this case, a female

- specific body weight of 69 kg

was used. While the endpoint of concern, brain AChE inhibition, is not sex

- specific, the female

specific body weight was used to protect for pregnant women due to uncertainty in the human

dose

- response relationship for neurodevelopmen tal effects (see Section 4.4). Dermal and incidental oral risk estimates for children (1 to <2 years old) were combined because the toxicity endpoint for each route of exposure is same (i.e., i nhibition of brain AChE ) . The total applicable

LOC is 100 0 , t herefore MOEs < 100 0 represent risk estimates of concern.

Adult dermal and children’s (1 to < 2 year old) dermal and incidental oral risk estimates related to spray drift exceed HED’s LOC (MOEs < 100 0 ) at a range of distances from the edge of the

field depending on the spray drift scenario. These a re summarized in Table 8. 1 .1 . A ll drift calculations are provided in the most recent ORE memo ( K. Lowe; 15

- SEP

- 2015 ; D418589 ).

14 AgDrift ® allows for consideration of even finer spray patterns characterized as very fine to fine. However, this spray pattern was not selected as the common screening basis since it is used less commonly for most agriculture. If assessors identify this use patt ern it should be used as the screening criteria and deposition values associated with it are provided in Table 1 below. Justification for including this spray quality should be included in any assessment based on specific label directions for its use.Dimethoate Human Health Risk Assessment DP No. D416010

Page 50 of 104 

### Results indicate that the major risk concern is from aerial applications. Appro priate drift reduction technologies such as changing the spray type/nozzle configuration to coarser spray applications may result in less drift and reduced risk concerns (i.e., higher MOEs) from aerial applications. Similarly, using coarser sprays and low ering boom height for groundboom sprayers reduces risk concerns.

Table 8. 1 .1

. Summary of Spray Drift Buffers for Dimethoate.

Crop Category Crops Application rate (lb ai/A) Adult Buffer Summary Children 1 < 2 years Buffer Summary (Dermal + Incidental Oral) Buffers Necessary to reach MOE of

100 0 Buffers Necessary to reach MOE of

100 0

Aerial Groundboom Airblast Aerial Groundboom Airblast

Forestry Cottonwoods grown

for pulp 2 100

- >300 NA

NA >300 NA

NA High Acreage Crops Alfalfa (field and

seed crop), Beans (fresh, snap, lima, dry, not cowpeas), Corn (field and popcorn), Cotton, Grass grown for seed, Potatoes, Safflower, Sorghum, Soybeans,

Wheat 0.5 25

- >300 0

- 25 125

- >300 10

- 150

Typical Acreage Crops Brussels sprouts 1 50

- >300 0

- 50 200

- >300 25

- 250

Asparagus, Broccoli, Cauliflower, Celery, Garbanzo beans, Lentils, Melons, Peas,
Tomatoes,

Watermelon 0.5 10

- >300 0

- 10 125

- >300 10

- 125

Peas, dry; Peas, succulent; Peppers 0.33 0

- 200 0

- 10 75

- >300 10

- 75

Kale, Mustard greens, Turnip 0.25 0

- 150 0

- 10 75

- >300 10

- 75

Peas 0.16 0

- 75 0 50

- >300 0

- 50

Nurseries /

Orchard Ornamentals in

outdoor nurseries 4.15

NA 0

- 100

NA 25

- 250

Citrus

- non

- bearing and nursery stock, Cherries (preharvest

and postharvest),

Christmas tree nurseries, Citrus, Pears (including non

bearing and nursery stock) 1 0

- 25 0

- 100

Lupine 0.5 0

- 10 0

- 75

Orchard Pecans 0.33 0

- 10 0

- 50



### 9.0 Aggregate Exposure/Risk Characterization

In accordance with the FQPA, HED must consider and aggregate (add) pesticide exposures and risks from three major sources: food, drinking water, and residential exposures. In an aggregate assessment, exposures from relevant sources are added together and compared to quantitative estimates of hazard (e.g., a NOAEL or PAD), or the risks themselves can be aggregated. WhenDimethoate Human Health Risk Assessment DP No. D416010

Page 51 of 104 

### aggregating exposures and risks from various sources, HED considers both the route and duration of exposure. The registered dimethoate us es are not anticipated to result in residential

exposure and thus t he acute and steady

- state dietary exposure estimates provided in Section 5.4.3

and 5.4.4 represent the acute and steady

- state aggregate exposure.
Dimethoate is classified as a Group C carci nogen (possible human carcinogen)

. Quantification of risk using a non

- linear approach will adequately account for all chronic toxicity, including carcinogenicity that could result from exposure to dimethoate.

10.0 Cumulative Exposure/Risk Characterization

OP s, like dimethoate/omethoate, share the ability to inhibit AChE through phosphorylation of the serine residue on the enzyme leading to accumulation of acetylcholine and ultimately cholinergic neurotoxicity. This shared MOA/AOP is the basis for the OP comm on mechanism grouping per

OPP’s Guidance For Identifying Pesticide Chemicals and Other Substances that have a Common Mechanism of Toxicity (USEPA, 1999). The 2002 and 2006 CRAs used brain AChE inhibition in female rats as the source of dose response data for the relative potency factors and PODs for each OP, including dimethoate/omethoate. Prior to the completion of Registration Review, OP P will update the OP CRA on AChE inhibition to incorporate new toxicity and exposure

information available since 2006.

As described in Section 4.4, OPP has retained the FQPA Safety Factor for OPs, including dimethoate/omethoate, due to uncertainties asso ciated with neurodevelopmental effects in children and exposure to OPs. There is a lack of an established MOA/AOP for the neurodevelopment outcomes which precludes the agency from formally establishing a common mechanism group per the Guidance For Identif ying Pesticide Chemicals and Other Substances that have a Common Mechanism of Toxicity (USEPA, 1999) based on that outcome. Moreover,

the lack of a recognized MOA/AOP and other uncertainties with exposure assessment in the epidemiology studies prevent the agency from establishing a causal relationship between OP exposure and neurodevelopmental outcomes. The agency will continue to evaluate the epidemiology studies associated with neurodevelopmental outcomes and OP exposure prior to

the release of the revi sed DRA. During this period, the agency will determine whether or not it is appropriate to apply the draft guidance document entitled, Pesticide Cumulative Risk Assessment: Framework for Screening Analysis for the neurodevelopment outcomes.

11.0 Occupational Exposure/Risk Characterization

11 .1 Short

- and Intermediate

- T erm Handler Risk

HED uses the term handlers to describe those individuals who are involved in the pesticide application process. HED believes that there are distinct job functions or tasks related to applications and exposures can vary depending on the specifics of each task. Job requirements (amount of chemical used in each application), the kinds of equipment used, the target being treated, and the level of protection used by a handler can cause exposure levels to differ in a manner specific to each application event.

For occupational handlers, exposure is anticipated to be to the parent, dimethoate, only. The dermal route of exposure is assessed using a dimethoate

- specific t oxicity study; therefore, no TAFs were used in the dose calculations. The inhalation route of exposure is assessed using anDimethoate Human Health Risk Assessment DP No. D416010

Page 52 of 104 

### omethoate

- specific toxicity study since a dimethoate

- specific inhalation toxicity study is not

available. No TAFs were used in the inhalation dose calculations, but it should be noted that the risk estimates presented are representative of exposure to the more toxic metabolite, omethoate, and, therefore, are conservative risk estimate s of potential exposure to dimethoate.

The quan titative exposure/risk assessment developed for occupational handlers is based on the following scenarios, which cover all the registered uses of dimethoate:

 Mixing/loading liquids and WSPs to support aerial applications,

 Mixing/loading liquids and WSPs to support airblast applications,

 Mixing/loading liquids to support chemigation applications,

 Mixing/loading liquids and WSPs to support groundboom applications,

 Applying sprays with aircraft,

 Applying sprays with groundboom equipment,

 Applying sprays with airblast equipment,

 Flagging to support aerial spray applications,

 Mixing/loading/applying liquids via backpack,

 Mixing/loading/applying liquids via mechanically

- pressurized handgun, and

 Mixing/loading/applying liquids via manually

- pressurized handwand.

Occupational Handler Exposure Data and Assumptions

A series of assumptions and exposure factors served as the basis for completing the occupational

h andler risk assessments. A ssumption s and factor s, as well as algorithms used to estimate non

c ancer exposure and dose for occupational handlers are detailed in the most recent ORE memo (K. Lowe; 15

- SEP

- 2015 ; D418589).

The steady

- state approach is appropriate for dimethoate given the toxicological and exposure profile. The steady

- state endpoint selection for dimethoate overlaps with HED’s traditional

short

- term exposure duration endpoint selection and is considered health protective for occupational handlers that apply commercially over longer periods of time (i.e., intermediate

term exposures).

Most of the dimethoate registered labels require handlers to wear a single layer of clothing ( long

sleeved shirt and long pants), shoes plus socks, protective eyewear (either goggles or face shield), chemical

- resistant gloves, a National Institute for Occ upational Safety and Health ( NIOSH )

- approved dust/mist filtering respirator with Mine Safety and Health Administration ( MSHA ) /NIOSH approval number prefix TC

- 21C or a NIOSH

- approved respirator with any N, R, P, or HE filter, and a chemical

- resistant apron when mixing, loading, cleaning up spills, or equipment.

For adults, when an endpoint is not sex

- specific (i.e., the endpoints are based on developmental or fetal effects) a body weight of 80 kg is typically used in risk assessment; however, in this case

, a female

- specific body weight of 69 kg was used. While the endpoint of concern, brain AChE inhibition, is not sex

- specific, the female

- specific body weight was used to protect for pregnant women due to uncertainty in the human dose

- response relationship for neurodevelopmental effects (see Section 4.4).Dimethoate Human Health Risk Assessment DP No. D416010

Page 53 of 104 

### Dermal and inhalation risk estimates were combined in this assessment, since the toxicological effects for these exposure routes were similar. The occupational handler exposure and risk

estimates indic ate that the dermal and inhalation combined MOEs are of concern to HED (i.e.,

MOE s ≤ 100 0 ) for most scenarios assuming the use of label

- required PPE (noted by the highlighted column in Table 11 .1.1

– single layer of clothing, gloves and a PF5 respirator)

. As was noted above, the inhalation risk estimates are considered to be a conservative estimate of exposure to dimethoate residues considering the inhalation POD was selected from an omethoate toxicity study. Only five scenarios (out of 40) reach an MOE above the LOC of 1000 at some level of PPE (above what is currently required on the labels) or with engineering controls.

HED has no data to assess exposures to pilots using open cockpits. The only data available is for exposure to pilots in enclosed coc kpits. Therefore, risks to pilots are assessed using the engineering control (enclosed cockpits) and baseline attire (long

- sleeve shirt, long pants, shoes, and socks); per the Agency’s Worker Protection Standard stipulations for engineering controls, pilo ts are not required to wear protective gloves for the duration of the application. With this level of protection, there are no risk estimates of concern for applicators.

The Agency matches quantitative occupational exposure assessment with appropriate characterization of exposure potential. While HED presents quantitative risk estimates for human flaggers where appropriate, agricultural aviation has changed dramatically over the past

two decades. According the 2012 National Agricultural Av iation Association (NAAA) survey of their membership, the use of Global Positioning System (GPS) for swath guidance in agricultural aviation has grown steadily from the mid

- 1990s

. Over the same time period, the use of human flaggers for aerial pesticide a pplications has decreased steadily from ~15% in the late 1990s to only 1% in the most recent (2012) NAAA survey. The Agency will continue to monitor all available information sources to best assess and characterize the exposure potential for human flagger s in agricultural aerial applications. HED recommends that the PPE on the registered dimethoate labels for flaggers be revised to reflect the requirements identified above (and

in Table 9 .1.1) to reach acceptable MOEs, or that flaggers be prohibited on th e label.Dimethoate Human Health Risk Assessment DP No. D416010

Page 54 of 104 Table 11. 1.1. Occupational Handler Non

- Cancer Exposure and Risk Estimates for Dimethoate

.

Exposure

Scenario Crop or Target 1 Dermal Unit Exposure
(μg/lb ai) 2 Inhalation

Unit Exposure
(μg/lb ai) 2 Maximum

Application

Rate 3 Area

Treated 4 Total MOE 5 (LOC = 100 0 )

SL/No G

No

- R SL/G

No

- R DL/G

No

- R SL/No G

PF5 R SL/G

PF5

- R DL/G

PF5

- R SL/No G

PF10 R SL/G

PF10

- R DL/G

PF10

- R EC

Mixer/Loader

M/L liquids for aerial applications

and c hemigation 8 Nursery

SL/No G 220

SL/G 37.6

DL/G 29.1

EC 8.6 No

- R 0.219

PF5 R 0.0438

PF10 R 0.0219

EC 0.083 1 lb ai/A 60 A 67 130 140 98 360 420 100 450 540 610

Orchard 6 0.33 lb ai/A

350 A 34 70 74 49 190 210 52 240 280 320

1.0 lb ai/A 11 24 25 16 63 72 17 80 95 110

1.33 lb ai/A 8.6 17 18 12 46 52 13 59 69 78

Typical field crops 7 0.5 lb ai/A 22 46 48 32 120 140 34 150 190 210

1 lb ai/A 11 24 25 16 63 72 17 80 95 110

High

- acreage field

crops 0.5 lb ai/A 1200 A 6.7 13 14 9.8 36 42 10 45 54 61

Forestry (aerial only) 2 lb ai/A 7500 A 0.26 0.54 0.57 0.38 1.5 1.7 0.4 1.8 2.2 2.4

M/L liquids for

airblast applications Nursery 4.15 lb ai/A 20 A 48 100 110 68 260 300 72 330 440 440

Orchard 1.33 lb ai/A 40 A 74 150 160 110 410 470 110 510 610 690

M/L liquids for groundboom applications Nursery 0.5 lb ai/A 60 A 130 270 290 190 700 820 200 890 1,100 1,200

Typical field crops 2 lb ai/A 80 A 25 51 53 36 130 150 38 170 210 230

High

- acreage field

crops 0.5 lb ai/A 200 A 39 79 83 56 220 250 59 270 320 370

M/ L WSP for aerial applications Orchard

EC 9.8 EC 0.24 1 lb ai/A 350 A ND ND ND ND ND ND ND ND ND 42

High

- acreage field

crops 0.5 lb ai/A 1,200 ND ND ND ND ND ND ND ND ND 24

M/L WSP for

airblast applications Orchard 1 lb ai/A 40 A ND ND ND ND ND ND ND ND ND 370

M/L WSP for groundboom applications High

- acreage field

crops 0.5 lb ai/A 200 A ND ND ND ND ND ND ND ND ND 140Dimethoate Human Health Risk Assessment DP No. D416010

Page 55 of 104 Table 11. 1.1. Occupational Handler Non

- Cancer Exposure and Risk Estimates for Dimethoate

.

Exposure

Scenario Crop or Target 1 Dermal Unit Exposure
(μg/lb ai) 2 Inhalation

Unit Exposure
(μg/lb ai) 2 Maximum

Application

Rate 3 Area

Treated 4 Total MOE 5 (LOC = 100 0 )

SL/No G

No

- R SL/G

No

- R DL/G

No

- R SL/No G

PF5 R SL/G

PF5

- R DL/G

PF5

- R SL/No G

PF10 R SL/G

PF10

- R DL/G

PF10

- R EC

Applicator

Applying sprays

via aerial equipment Nursery

EC 2.08 EC 0.0049 1 lb ai/A 60 A ND ND ND ND ND ND ND ND ND 2,800

Orchard 1.33 lb ai/A 350 A ND ND ND ND ND ND ND ND ND 360

Typical field crops 1 lb ai/A ND ND ND ND ND ND ND ND ND 480

High

- acreage field

crops 0.5 lb ai/A 1,200 A ND ND ND ND ND ND ND ND ND 280

Forestry 2 lb ai/A 7,500 A ND ND ND ND ND ND ND ND ND 11

Applying sprays

via airblast equipment 9 Nursery SL/No G 1,770

SL/G 1,590

DL/G 1,480

EC 14.6 No

- R 4.71

PF5 R 0.942

PF10 R 0.471

EC 0.068 4.15 lb ai/A 20 A 2.2 2.2 2.2 5.7 6.2 6.2 7.1 7.9 7.9 170

Orchard 1.33 lb ai/A 40 A 3.4 3.5 3.5 8.9 9.3 9.9 11 12 13 260

Applying sprays via groundboom equipment Nursery SL/No G 78.6

SL/G 16.1

DL/G 12.6

EC 5.1 No

- R 0.34

PF5 R 0.068

PF10 R 0.034

EC 0.043 0.5 lb ai/A 60 A 93 110 110 280 460 470 380 800 850 2,300

Typical field crops 2 lb ai/A 80 A 17 19 19 52 84 87 71 150 160 430

High

- acreage field

crops 0.5 lb ai/A 200 A 27 31 31 85 140 140 120 230 250 680

Flagger

Flagger Nursery

SL/No G 11

SL/G 12

DL/G 10.6 No

- R 0.35

PF5 R 0.07

PF10 R 0.035 1 lb ai/A 60 A 170 170 170 650 630 660 1,000 950 1,000 ND

Orchard 1.33 lb ai/A

350 A 22 22 22 83 81 84 130 120 130 ND

Typical field crop 1 lb ai/A 29 29 30 110 110 110 170 160 170 ND

High

- acreage field

crop 0.5 lb ai/A 59 58 59 220 220 220 340 320 350 ND

Mixer/Loader/Applicator

M/L/A liquids ground applications (soil directed) with backpack Orchard

SL/No G 8,260 SL/G 8,260 DL/G 4,120 No

- R 2.58

PF5 R 0.516

PF10 R 0.258 0.005 lb ai/gal

40 gal 710 710 1,200 820 820 1,600 830 830 1,600 ND

Christmas tree farm 0.025 lb ai/gal 140 140 250 160 160 320 170 170 330 ND

Forestry 0.04 lb ai/gal 92 92 150 110 110 200 110 110 200 ND

Nursery 0.08 lb ai/gal 45 45 79 51 510 100 52 52 110 NDDimethoate Human Health Risk Assessment DP No. D416010

Page 56 of 104 Table 11. 1.1. Occupational Handler Non

- Cancer Exposure and Risk Estimates for Dimethoate

.

Exposure

Scenario Crop or Target 1 Dermal Unit Exposure
(μg/lb ai) 2 Inhalation

Unit Exposure
(μg/lb ai) 2 Maximum

Application

Rate 3 Area

Treated 4 Total MOE 5 (LOC = 100 0 )

SL/No G

No

- R SL/G

No

- R DL/G

No

- R SL/No G

PF5 R SL/G

PF5

- R DL/G

PF5

- R SL/No G

PF10 R SL/G

PF10

- R DL/G

PF10

- R EC

M/L/A liquids

broadcast applications with backpack Christmas tree farm SL/No G

58400

SL/G 30500

DL/G 16900 No

- R 69.1

PF5 R 13.8

PF10 R 6.9 0.025 lb ai/gal 17 25 34 22 40 64 23 43 72 ND

Nursery 0.08 lb ai/gal 5 8 11 7 12 20 7 13 23 ND

Forestry SL/No G 8,260

SL/G 8,260 DL/G 4,120 No

- R 2.58

PF5 R 0.516

PF10 R 0.258 0.04 lb ai/gal 11 16 21 14 25 40 14 27 45 ND

M/L/A liquids foliar applications with manually

pressurized handgun Christmas tree farm SL/No G 100,000

SL/G 430

DL/G 365 No

- R 30

PF5 R 6

PF10 R 3 0.025 lb ai/gal

40 gal 13 120 130 14 550 560 14 920 970 ND

Nursery 0.08 lb ai/gal 4 39 40 4.3 170 180 4.4 290 310 ND

M/L/A liquids foliar applications with mechanically

pressurized handgun Orchard

SL/No G 6050

SL/G 2050

DL/G 1360 No

- R 8.68

PF5 R 1.74

PF10 R 0.87 0.0025 lb ai/gal 1,000 gal 61 110 130 83 210 280 88 230 330 ND Christmas tree farm

Nursery

Typical field crop

M/L/A liquids drench/soil/ground

directed applications with mechanically

pressurized handgun Orchard

Nursery

Typical field crop

Shaded column = current PPE required on labels. Bold MOE values indicate the LOC has been exceeded with label

- recommended and/or additional PPE.

1

. Typical field crops include asparagus, broccoli, cauliflower, Brussels sprouts, celery, endive, leaf lettuce, Swiss chard, garbanzo beans, kale, lentils, melons, mustard greens, peas, peppers, tomatoes, turnips, and watermelon. High

- acreage field crops included alfalfa, beans, corn, cotton, grass grown for seed, potatoes, s afflower, sorghum, soybeans, and wheat

. Orchard crops include cherries, citrus, pears, and pecans. Nurseries include citrus, lupine, ornamentals in outdoor nurseries. Forestry includes trees grown for pulp.

2

. Based on the “Occupational Pesticide Handle r Unit Exposure Surrogate Reference Table” ( August 2015 ); Level of mitigation: SL/No G No

- R = Single layer clothing, no gloves, no respirator;

SL/G No

- R = Single layer clothing, gloves, no respirator; DL/G No

- R = Double layer clothing, gloves, no respirat or; SL/No G PF5 R = Single layer clothing, no gloves, PF5 respirator; SL/G PF5 R = Single layer clothing, gloves, PF5 respirator; DL/G PF5 R = Double layer clothing, gloves, PF5 respirator; SL/No G PF10 R = Single layer clothing, no gloves, PF10 respirator ; SL/G PF10 R = Single layer clothing, gloves, PF10 respirator; DL/G PF10 R = Double layer clothing, gloves, PF10 respirator; EC = Engineerin g Controls. ND = no data.

3

. Based on registered labels.

4

. Exposure Science Advisory Council Policy #9.1.

5

. Tota l MOE = 1 ÷ (1/Dermal MOE) + (1/Inhalation MOE)

. 6

. Application rates for orchard crops: Pecans (0.33 lb ai/A); Pears and Citrus (1 lb ai/A) ; Cherries (1.33 lb ai/A).

7

. Dimethoate 400 label (67760

- 118); Label lists maximum application rate for Brussels Sprout as 0.5 lb ai/A, but also indicates 38.2 fl oz. product/A, which is 1 lb ai/A.Dimethoate Human Health Risk Assessment DP No. D416010

Page 57 of 104 8

. Only the scenarios assessed at 350 A are applicable for c hemigation applications.

9

. For airblast applications to nurseries and orchards, additional PPE could include chemical

- resistant headgear (CRH). The addition of CRH resulted in MOEs that exceed HED’s LOC: Nursery

- SL/G/CRH = 24, DL/G/CRH

- 27; Orchard SL/G/CRH = 37, DL/G/CRH

- 41.Dimethoate Human Health Risk Assessment DP No. D416010

Page 58 of 104 

### 11 .2 Short

- /Intermediate

- Term Post

- Application Risk

HED uses the term post

- application to describe exposures that occur when individuals are present in an environment that has been previously treated with a pesticide (also referred to as re

entry exposure). Such exposures may occur when workers enter previously tre ated areas to perform job functions, including activities related to crop production, such as scouting for pests or harvesting. Post

- application exposure levels vary over time and depend on such things as the type of activity, the nature of the crop or ta rget that was treated, the type of pesticide application, and the chemical’s degradation properties. In addition, the timing of pesticide applications, relative to harvest activities, can greatly reduce the potential for post

- application exposure.

For oc cupational post

- application workers, exposure is anticipated to be to both dimethoate and omethoate. Since the dermal route of exposure is assessed using a dimethoate

- specific toxicity study, the omethoate residues have been adjusted by a TAF to account f or the increased potency

of omethoate.

11 .2.1 Occupational Post

- application Inhalation Exposure/Risk Estimates

There are multiple potential sources of post

- application inhalation exposure to individuals performing post

- application activities in previou sly treated fields. These potential sources include volatilization of pesticides and resuspension of dusts and/or particulates that contain pesticides. The Agency sought expert advice and input on issues related to volatilization of pesticides from its F IFRA SAP in December 2009, and received the SAP’s final report on March
2, 2010 15 

### . The Agency has evaluated the SAP report and has developed a Volatilization Screening Tool and a subsequent Volatilization Screening Analysis 16



### . During Registration Review, the A gency will utilize this analysis to determine if data (i.e., flux studies ) or further analysis is required for dimethoate

.

In addition, the Agency is continuing to evaluate the available post

- application inhalation

exposur e data generated by the ARTF . Given these two efforts, the Agency will continue to identify the need for and, subsequently, the way to incorporate occupational post

- application inhalation exposure into the A gency's risk assessments.

11 .2.2 Occupational Post

- application Dermal Exposure/Risk Estimates

Occupational Post

- application Dermal Exposure Data and Assumptions

A series of assumptions and exposure factors served as the basis for completing the occupational

post

- application risk assessments. A ssump tion s and factor s, as well as the algorithms used to

estimate non

- cancer exposure and dose for occupational post

- application workers are detailed in the most recent ORE memo (K. Lowe; 15

- SEP

- 2015 ; D418589).

15 h ttp://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html

16 http://www.regulations.gov/#!docketDetail;D=EPA

- HQ

- OPP

- 2014

- 0219.Dimethoate Human Health Risk Assessment DP No. D416010

Page 59 of 104 

### The steady

- state approach is appropriate for d imethoate given the toxicological and exposure profile. The “ steady

- state ” endpoint selection for dimethoate overlaps with HED’s traditional

short

- term exposure duration endpoint selection as well as being appropriately health protective

for workers that are exposed over longer periods of time (i.e., intermediate

- term exposures).

For adults, when an endpoint is not sex

- specific (i.e., the endpoints are based on developmental or fetal effects) a body weight of 80 kg is typically used in risk assessment; however, in this case,

a female

- specific body weight of 69 kg was used. While the endpoint of concern, brain AChE inhibition, is not sex

- specific, the female

- specific body weight was used to protect for pregnant women due to uncertainty in the human dose

- response relationship for neurodevelopmental effects (see Section 4.4).

Chemical

- specific DFR data have been submitted for dimethoate. Four studies were submitted that examined residues of dimethoate and its metabolite, omethoate, on the following crop s: grapes (MRID 44788201), tomato (MRID 44690302), lettuce (MRID 44690301), and apple (MRID 44827601). All four studies have been reviewed by HED and found to be acceptable for risk assessment. The grape DFR data were not used in this risk assessment si nce dimethoate is no longer registered for use on grapes.

A summary of how the DFR data were used is summarized in Table 11 .2.2.1 and discussed in the most recent ORE memo (K. Lowe; 15

- SEP

- 2015 ; D418589).

Table 11 .2.2.1. Summary of DFR Data Use in Occ upational Post

- application Assessment for Dimethoate Crop for which DFR

data available Locations included in study Crops for which DFR data used as surrogate

Apple Michigan (MI)

- non

- arid

New York (NY)

- non

- arid Washington (WA)

- arid Cherries, Christmas trees, Forestry, Grapefruit, Lemons, Ornamentals (nursery crop), Orange, Pear, Pecan

Lettuce Pennsylvania (PA)

- non

- arid

Florida (FL)

- non

- arid California (CA)

-- arid Kale, Leaf lettuce, Mustard greens, Green pea, Swiss chard, Turnip

Tomato Pennsylvania (PA)

- non

- arid

Florida (FL)

- non

- arid California (CA)

-- arid Alfalfa, Asparagus, Dry beans and peas, Broccoli, Brussels sprouts, Cauliflower, Celery, Field Corn, Pop corn, Cotton, Forage crop, Bell Pepper, Potato, Safflower, Grain sorghum, Soybean, Tomato, Watermelon, Spring wheat, Winter wheat



### Each of the studies measured the amount of dimethoate residues remaining on treated leaves following applications, and also measured, when present, omethoate residues. Typically, when

omethoate was present in the studies, it peaked in quantity a few days after the application, and then gradually dissipated over time. Dimethoate residues peaked immediately after application and dissipated over time thereafter. In general, omethoate was a significan t factor in arid areas (i.e., areas where the average annual rainfall is less than 25 inches per year). Since dissipation rates at the arid sites were significantly different from those at the non

- arid sites, the results are reported separately for all st udy sites.Dimethoate Human Health Risk Assessment DP No. D416010

Page 60 of 104 

### As mentioned earlier, omethoate is a metabolite of dimethoate and is 3 times more toxicologically potent than dimethoate. Since the POD for the dermal route of exposure was chosen from a dimethoate toxicity study, a TAF of 3 was chosen to acco unt for the increased potency of omethoate in exposure calculations. A total toxic residue approach was used whereby residues of omethoate were adjusted by the TAF and total residues (dimethoate + adjusted omethoate) were include d in exposure calculations 17 

### . In those studies where omethoate was not found, the post

- application risks were assessed using only the dimethoate residues.

Occupational Post

- application Non

- Cancer Dermal Risk Estimates

The post

- application exposure scenarios associated with the registered uses of dimethoate are

summarized in Tables 11 .2.2.2 through 11 .2.2.4. The results of the risk assessment for post

application exposures indicate that the location and/or the environme ntal conditions (i.e., arid

versus non

- arid) near the time of application influence the length of time following application

until risks are below HED’s LOC (i.e., MOEs are greater than or equal to 100 0 ) as does the type of plant to which the application i s directed. For most crops, the post

- application assessment indicates that following applications in arid areas (i.e., outdoor areas where average annual rainfall is less than 25 inches), residues persist longer than in non

- arid areas.

For the orchar d crops, using the apple DFR data, there are risks of concern for most of the high

contact post

- application activities associated with each crop (e.g., hand harvesting, handset irrigation, etc). Some crop/activity combinations do not reach an acceptable M OE (LOC = 1000) even up to 30 days after application.

For the field crops using the lettuce DFR data, there are risks of concern for certain high contact activities (e.g., hand harvesting, hand weeding, etc). Some crop/activity combinations do not

reac h an acceptable MOE (LOC = 1000) until 7 days after application.

For the field crops using the tomato DFR data, there are risks of concern for certain high contact activities (e.g., hand harvesting, hand weeding, etc). Some crop/activity combinations do not reach an acceptable MOE (LOC = 1000) until 14 days after appli cation.

17 Total DFR, ug/cm 2 = [ (Omethoate residue, ug/cm 2 ) * TAF] + [Dimethoate residue, ug/cm 2 )Dimethoate Human Health Risk Assessment DP No. D416010

Page 61 of 104 Table 11 .2.2.2 . Dimethoate Occupational Post

- application Risk Estimates Using Chemical

- specific Data ( Apples/ MRID 44827601 )

Crop Policy

Crop Group Category Application

Rate (lb ai/A) Activities Transfer

Coefficients (cm 2 /hr ) Time Following

Application (days, unless specified) DFR 1 Dermal Dose (mg/kg/day) 2 MOE 3 (LOC = 100 0 )

Non

- Arid Arid Non

- Arid Arid Non

- Arid Arid Non

- Arid Arid

APPLE STUDY DATA

MI NY WA MI NY WA MI NY WA MI NY WA

Cherry Tree,

"fruit",

deciduous 1.33 Orchard maintenance ; Weeding, Hand ; Bird

Control ; Propping 100 12 hr 1.89 2.35 2.70 0.022 0.027 0.031 920 740 640

1 3 6 1.64 1.72 1.63 0.019 0.020 0.019 1,100 1,000 1,100

Transplanting 230 12 hr 1.89 2.35 2.70 0.050 0.063 0.072 400 320 280

7 11 15 0.72 0.74 0.76 0.019 0.020 0.020 1,000 1,000 1

, 000

Scouting ; Pruning,

Hand ; Training 580 12 hr 1.89 2.35 2.70 0.127 0.158 0.182 160 130 110

14 20 26 0.28 0.29 0.30 0.019 0.019 0.022 1,100 1,000 1,000

Harvesting, Hand 1400 12 hr 1.89 2.35 2.70 0.306 0.382 0.439 66 53 46

20 29 30 0.12 0.11 0.21 0.020 0.018 0.035 1000 1,100 580

Thinning Fruit 3600 12 hr 1.89 2.35 2.70 0.787 0.982 1.128 26 21 18

27 30 30 0.05 0.10 0.21 0.019 0.042 0.089 1,000 480 230

Christmas

tree Tree,

"fruit",

evergreen 1 Weeding, Hand ; Grading/Tagging 100 12 hr 1.42 1.77 2.03 0.016 0.021 0.024 1,200 980 860

N/A 1 2 N/A 1.59 1.71 N/A 0.018 0.020 N/A 1,100 1,000

Transplanting 230 12 hr 1.42 1.77 2.03 0.038 0.047 0.054 530 430 370

5 9 12 0.71 0.69 0.74 0.019 0.018 0.020 1,100 1,100 1,000

Scouting ; Shaping 580 12 hr 1.42 1.77 2.03 0.095 0.119 0.137 210 170 150

12 17 23 0.27 0.30 0.29 0.018 0.020 0.019 1,100 1,000 1,000

Harvesting, Hand 1400 12 hr 1.42 1.77 2.03 0.230 0.287 0.330 88 70 61

18 26 30 0.12 0.12 0.16 0.020 0.019 0.026 1,000 1,100 780

Irrigation (hand set) 1900 12 hr 1.42 1.77 2.03 0.312 0.390 0.447 65 52 45

20 29 30 0.09 0.08 0.16 0.020 0.019 0.035 1,000 1,100 570

Forestry Unassigned 2 Weeding, Hand 100 12 hr 2.84 3.54 4.06 0.033 0.041 0.047 610 490 430

4 7 10 1.64 1.70 1.74 0.019 0.020 0.020 1,100 1,000 1,000Dimethoate Human Health Risk Assessment DP No. D416010

Page 62 of 104 Table 11 .2.2.2 . Dimethoate Occupational Post

- application Risk Estimates Using Chemical

- specific Data ( Apples/ MRID 44827601 )

Crop Policy

Crop Group Category Application

Rate (lb ai/A) Activities Transfer

Coefficients (cm 2 /hr ) Time Following

Application (days, unless specified) DFR 1 Dermal Dose (mg/kg/day) 2 MOE 3 (LOC = 100 0 )

Non

- Arid Arid Non

- Arid Arid Non

- Arid Arid Non

- Arid Arid

APPLE STUDY DATA

MI NY WA MI NY WA MI NY WA MI NY WA

Transplanting 230 12 hr 2.84 3.54 4.06 0.076 0.094 0.108 270 210 190

10 15 20 0.72 0.74 0.75 0.019 0.020 0.020 1,100 1,000 1,000

Pruning, Hand 580 12 hr 2.84 3.54 4.06 0.191 0.238 0.273 110 85 74

17 24 30 0.28 0.29 0.32 0.019 0.019 0.018 1,100 1,000 940

Harvesting, Seed Cone (Conifers) 1400 12 hr 2.84 3.54 4.06 0.460 0.574 0.659 44 35 31

23 30 30 0.12 0.15 0.32 0.020 0.025 0.044 1,000 810 390

Irrigation (hand set) 1900 12 hr 2.84 3.54 4.06 0.625 0.779 0.895 32 26 23

25 30 30 0.09 0.15 0.32 0.020 0.034 0.060 1,000 600 290

Harvesting, Seedling

Production 6700 12 hr 2.84 3.54 4.06 2.203 2.749 3.156 9.2 7.3 6.4

30 30 30 0.05 0.15 0.32 0.036 0.119 0.210 560 170 81

Grapefruit

, Lemon, Orange Tree,

"fruit",

evergreen 1 Orchard maintenance ; Weeding, Hand ; Baiting/Trapping ; Weeding, Hand 100 12 hr 1.42 1.77 2.03 0.016 0.08 0.024 1,200 980 860

N/A 1 2 N/A 1.59 1.71 N/A 0.018 0.020 N/A 1,100 1,000

Transplanting 230 12 hr 1.42 1.77 2.03 0.038 0.047 0.054 530 430 370

5 9 12 0.71 0.69 0.74 0.019 0.018 0.020 1,100 1,100 1,000

Scouting ; Pruning,

Hand 580 12 hr 1.42 1.77 2.03 0.095 0.119 0.137 210 170 150

12 17 23 0.27 0.30 0.29 0.018 0.020 0.019 1,100 1,000 1,000

Harvesting, Hand 1400 12 hr 1.42 1.77 2.03 0.230 0.287 0.330 88 70 61

18 26 30 0.12 0.12 0.16 0.020 0.019 0.26 1,000 1,100 780

Nursery Crop (Ornamentals,

Non

- bearing Plants) Unassigned 4.15 Harvesting, Hand ; Pruning, Hand ; Scouting ; Container Moving ; Weeding,

Hand ; Transplanting ; Grafting ; Propagating ; 230 12 hr 5.89 7.34 8.43 0.157 0.196 0.225 130 100 90

15 22 29 0.75 0.73 0.72 0.020 0.020 0.019 1,000 1,000 1,000Dimethoate Human Health Risk Assessment DP No. D416010

Page 63 of 104 Table 11 .2.2.2 . Dimethoate Occupational Post

- application Risk Estimates Using Chemical

- specific Data ( Apples/ MRID 44827601 )

Crop Policy

Crop Group Category Application

Rate (lb ai/A) Activities Transfer

Coefficients (cm 2 /hr ) Time Following

Application (days, unless specified) DFR 1 Dermal Dose (mg/kg/day) 2 MOE 3 (LOC = 100 0 )

Non

- Arid Arid Non

- Arid Arid Non

- Arid Arid Non

- Arid Arid

APPLE STUDY DATA

MI NY WA MI NY WA MI NY WA MI NY WA

Pinching ; Tying/Training

Irrigation (hand set) 1900 12 hr 5.89 7.34 8.43 1.296 1.617 1.857 16 12 11

30 30 30 0.10 0.32 0.67 0.021 0.070 0.147 950 290 140

1 Harvesting, Hand ;

Pruning, Hand ; Scouting ; Container Moving ; Weeding,

Hand ; Transplanting ; Grafting ; Propagating ; Pinching ; Tying/Training 230 12 hr 1.42 1.77 2.03 0.038 0.047 0.054 530 430 370

5 9 12 0.71 0.69 0.74 0.019 0.018 0.020 1,100 1,100 1,000

Irrigation (hand set) 1900 12 hr 1.42 1.77 2.03 0.312 0.316 0.447 65 52 45

20 29 30 0.03 0.08 0.14 0.020 0.019 0.035 1,000 1,100 570

Pear Tree,

"fruit",

deciduous 1 Orchard maintenance ; Weeding, Hand ; Propping 100 12 hr 1.42 1.77 2.03 0.016 0.021 0.024 1,200 980 860

N/A 1 2 N/A 1.59 1.71 N/A 0.018 0.020 N/A 1,100 1,000

Transplanting 230 12 hr 1.42 1.77 2.03 0.038 0.042 0.054 530 430 370

5 9 12 0.71 0.69 0.74 0.019 0.018 0.020 1,100 1,100 1,000

Scouting ; Pruning,

Hand ; Training 580 12 hr 1.42 1.77 2.03 0.095 0.107 0.137 210 170 150

12 17 23 0.27 0.30 0.29 0.018 0.020 0.019 1,100 1,000 1,000

Harvesting, Hand 1400 12 hr 1.42 1.77 2.03 0.230 0.287 0.330 88 70 61

18 26 30 0.12 0.12 0.16 0.020 0.019 0.026 1,000 1,100 780

Thinning Fruit 3600 12 hr 1.42 1.77 2.03 0.592 0.738 0.848 34 27 24

25 30 30 0.05 0.08 0.16 0.019 0.032 0.067 1,100 630 300

Pecan Tree, "nut" 0.33 Poling ; Orchard

maintenance ; Weeding,

Hand 100 12 hr 0.47 0.58 0.67 0.005 0.007 0.008 3,700 3,000 2,600Dimethoate Human Health Risk Assessment DP No. D416010

Page 64 of 104 Table 11 .2.2.2 . Dimethoate Occupational Post

- application Risk Estimates Using Chemical

- specific Data ( Apples/ MRID 44827601 )

Crop Policy

Crop Group Category Application

Rate (lb ai/A) Activities Transfer

Coefficients (cm 2 /hr ) Time Following

Application (days, unless specified) DFR 1 Dermal Dose (mg/kg/day) 2 MOE 3 (LOC = 100 0 )

Non

- Arid Arid Non

- Arid Arid Non

- Arid Arid Non

- Arid Arid

APPLE STUDY DATA

MI NY WA MI NY WA MI NY WA MI NY WA

Harvesting, Mechanical (shaking) 190 0.010 0.013 0.015 2,000 1,600 1,400

Transplanting 230 0.012 0.016 0.018 1,600 1,300 1,100

Pruning, Hand ; Scouting 580 0.031 0.039 0.045 640 510 450

4 7 10 0.27 0.28 0.29 0.018 0.019 0.019 1,100 1,100 1,000

Bold MOE values are below the LOC of 1000

. Shaded cells indicate the MOE is still below the LOC 30 days after application (i.e., an REI of >30 days would be necessary t o achieve a MOE greater than the LOC).

1

. DFR = Combined residues of dimethoa te and omethoate from an apple study, adjusted to account for application rate differences and for differences in toxicity of omethoate.

2

. Daily Dermal Dose = [DFR (μg/cm 2 ) × Transfer Coefficient × 0.001 mg/μg × 8 hrs/day]  BW ( 69 kg).

3

. MOE = POD (20.2 mg/kg/day) / Daily Dermal Dose.

Table 11.2.2.3 . Dimethoate Occupational Post

- application Risk Estimates Using Chemical

- specific Data (Lettuce /MRID 44690301 )

Crop Policy Crop

Group Category Application

Rate (lb ai/A) Activities Transfer

Coefficients (cm 2 /hr ) Time Following

Application (days, unless specified) DFR 1 Dermal Dose (mg/kg/day) 2 MOE 3 (LOC = 100 0 )

Non

- Arid Arid Non

- Arid Arid Non

- Arid Arid Non

- Arid Arid

LETTUCE STUDY DATA

PA FL CA PA FL CA PA FL CA PA FL CA

Kale , Leaf
Lettuce,

Mustard
Green,

Swiss

Chard Vegetable, leafy 0.25 Weeding, Hand ; Thinning Plants 70

12 hr 0.27 0.11 0.52 0.002 0.001 0.004 9,100 24,000 4,800

Scouting 210 0.007 0.003 0.013 3,000 7,800 1,600

Transplanting 230 0.007 0.003 0.014 2,800 7,200 1,500

Harvesting, Hand 1100 0.035 0.014 0.066 580 1,500 310

1 N/A 5 0.10 N/A 0.15 0.012 N/A 0.019 1,700 N/A 1,100

Irrigation (hand set) 1900 12 hr 0.27 0.11 0.52 0.060 0.023 0.114 340 870 180

2 1 7 0.03 0.04 0.09 0.007 0.009 0.020 2,800 2,300 1,000

0.16 Weeding, Hand 70 12 hr 0.17 0.07 0.33 0.001 0.001 0.003 14,000 37,000 7,500Dimethoate Human Health Risk Assessment DP No. D416010

Page 65 of 104 Table 11.2.2.3 . Dimethoate Occupational Post

- application Risk Estimates Using Chemical

- specific Data (Lettuce /MRID 44690301 )

Crop Policy Crop

Group Category Application

Rate (lb ai/A) Activities Transfer

Coefficients (cm 2 /hr ) Time Following

Application (days, unless specified) DFR 1 Dermal Dose (mg/kg/day) 2 MOE 3 (LOC = 100 0 )

Non

- Arid Arid Non

- Arid Arid Non

- Arid Arid Non

- Arid Arid

LETTUCE STUDY DATA

PA FL CA PA FL CA PA FL CA PA FL CA

Pea,

Green Field / row crop,

low / medium Scouting 210 0.004 0.002 0.008 4,700 12,000 2,500

Harvesting, Hand 1100 0.022 0.009 0.042 910 2,300 480

1 N/A 3 0.06 N/A 0.16 0.008 N/A 0.020 2,600 N/A 1,000

Irrigation (hand set) 1900 12 hr 0.17 0.07 0.33 0.039 0.015 0.073 520 1,400 280

1 N/A 6 0.06 N/A 0.08 0.013 N/A 0.017 1,500 N/A 1,200

Turnip Vegetable, "root" 0.25 Weeding, Hand ; Thinning Plants 70

12 hr 0.27 0.11 0.52 0.002 0.001 0.004 9,100 24,000 4,800

Scouting 210 0.007 0.003 0.013 3,000 7,800 1,600

Harvesting, Hand 1100 0.035 0.014 0.066 580 1,500 310

1 N/A 5 0.10 N/A 0.15 0.012 N/A 0.019 1,700 N/A 1,100

Irrigation (hand set) 1900 12 hr 0.27 0.11 0.52 0.060 0.023 0.114 340 870 180

2 1 7 0.03 0.04 0.09 0.007 0.009 0.020 2,800 2,300 1,000

Bold MOE values are below the LOC of 1000

. 1

. DFR = Combined residues of dimethoate and omethoate from a lettuce study , adjusted to account for application rate differences and for differences in toxicity of omethoate.

2

. Daily Dermal Dose = [DFR (μg/cm 2 ) × Transfer Coefficient × 0.001 mg/μg × 8 hrs/day]  BW ( 69 kg).

3

. MOE = POD (20.2 mg/kg/day) / Daily Dermal Dose.

Table 11.2.2.4 . Dimethoate Occupational Post

- application Risk Estimates Usin g Chemical

- specific Data (Tomato /MRID 44690302 )

Crop Policy Crop Group

Category Application

Rate (lb ai/A) Activities Transfer

Coefficients (cm 2 /hr ) Time Following

Application (days, unless specified) DFR 1 Dermal Dose (mg/kg/day) 2 MOE 3 (LOC = 100 0 )

Non

- Arid Arid Non

- Arid Arid Non

- Arid Arid Non

- Arid Arid

TOMATO STUDY DATA

PA FL CA PA FL CA PA FL CA PA FL CA

0.5 Scouting 1100 12 hr 0.48 0.66 0.36 0.061 0.084 0.046 330 240 440Dimethoate Human Health Risk Assessment DP No. D416010

Page 66 of 104 Table 11.2.2.4 . Dimethoate Occupational Post

- application Risk Estimates Usin g Chemical

- specific Data (Tomato /MRID 44690302 )

Crop Policy Crop Group

Category Application

Rate (lb ai/A) Activities Transfer

Coefficients (cm 2 /hr ) Time Following

Application (days, unless specified) DFR 1 Dermal Dose (mg/kg/day) 2 MOE 3 (LOC = 100 0 )

Non

- Arid Arid Non

- Arid Arid Non

- Arid Arid Non

- Arid Arid

TOMATO STUDY DATA

PA FL CA PA FL CA PA FL CA PA FL CA

Alfalfa , Dry Beans, Dry Peas, Forage Crop Field / row crop, low /

medium 2 2 4 0.06 0.11 0.16 0.008 0.006 0.020 2,500 1,500 1

, 000

Irrigation (hand set) 1900 12 hr 0.48 0.66 0.36 0.105 0.146 0.079 190 140 260

2 3 7 0.06 0.04 0.09 0.014 0.010 0.019 1,400 2,100 1,100

Asparagus Vegetable, stem / stalk 0.5 Weeding, Hand 70

12 hr 0.48 0.66 0.36 0.004 0.005 0.003 5,200 3,800 7,000

Scouting 210 0.012 0.016 0.009 1,700 1,300 2,300

Transplanting 230 0.013 0.018 0.010 1,600 1,100 2,100

Harvesting, Hand 1100 0.061 0.084 0.046 330 240 440

2 2 4 0.06 0.11 0.16 0.008 0.014 0.020 2,500 1,500 1,000

Irrigation (hand set) 1900 12 hr 0.48 0.66 0.36 0.105 0.146 0.079 190 140 260

2 3 7 0.06 0.04 0.09 0.014 0.010 0.019 1,400 2,100 1,100

Broccoli

, Cauliflower Vegetable, head and stem

Brassica 0.5 Transplanting 230 12 hr 0.48 0.66 0.36 0.013 0.018 0.010 1,600 1,100 2,100

Scouting Thinning Plants 330 0.018 0.025 0.014 1,100 800 1,500

N/A 1 N/A N/A 0.27 N/A N/A 0.010 N/A N/A 2

, 000 N/A

Weeding, Hand 1400 12 hr 0.48 0.66 0.36 0.077 0.107 0.058 260 190 350

2 2 6 0.06 0.11 0.10 0.010 0.017 0.017 2,000 1,200 1 ,2 00

Irrigation (hand set) 1900 12 hr 0.48 0.66 0.36 0.105 0.146 0.079 190 140 260

2 3 7 0.06 0.04 0.09 0.014 0.010 0.019 1,400 2,100 1,100

Scouting Harvesting, Hand Weeding, Hand 4200 12 hr 0.48 0.66 0.36 0.232 0.322 0.174 87 63 120

3 4 11 0.02 0.02 0.04 0.011 0.009 0.018 1,800 2

, 400 1,100

Brussels Sprouts Vegetable, head and stem

Brassica 1 Transplanting 230 12 hr 0.95 1.32 0.71 0.025 0.035 0.019 800 570 1,100

1 1 N/A 0.35 0.53 N/A 0.009 0.014 N/A 2,200 1,400 N/A

Scouting 330 12 hr 0.95 1.32 0.71 0.036 0.051 0.027 560 400 740Dimethoate Human Health Risk Assessment DP No. D416010

Page 67 of 104 Table 11.2.2.4 . Dimethoate Occupational Post

- application Risk Estimates Usin g Chemical

- specific Data (Tomato /MRID 44690302 )

Crop Policy Crop Group

Category Application

Rate (lb ai/A) Activities Transfer

Coefficients (cm 2 /hr ) Time Following

Application (days, unless specified) DFR 1 Dermal Dose (mg/kg/day) 2 MOE 3 (LOC = 100 0 )

Non

- Arid Arid Non

- Arid Arid Non

- Arid Arid Non

- Arid Arid

TOMATO STUDY DATA

PA FL CA PA FL CA PA FL CA PA FL CA

1 2 2 0.35 0.21 0.58 0.013 0.008 0.018 1,500 2,500 1 ,1 00

Irrigation (hand set) 1900 12 hr 0.95 1.32 0.71 0.210 0.291 0.157 96 69 130

3 3 10 0.05 0.09 0.09 0.010 0.019 0.020 2,000 1,100 1,000

Scouting Harvesting, Hand Topping Weeding, Hand 4200 12 hr 0.95 1.32 0.71 0.463 0.644 0.348 44 31 58

4 4 14 0.02 0.03 0. 04 0.008 0.017 0.020 2,500 1,200 1,000

Celery Vegetable, leafy 0.5 Weeding, Hand 70

12 hr 0.48 0.66 0.36 0.004 0.005 0.003 5,200 3,800 7,000

Scouting 210 0.012 0.016 0.009 1,700 1,300 2,300

Transplanting 230 0.013 0.018 0.010 1,600 1,100 2,100

Harvesting, Hand 1100 0.061 0.084 0.046 330 240 440

2 2 4 0.06 0.11 0.16 0.008 0.014 0.020 2,500 1,500 1,000

Irrigation (hand set) 1900 12 hr 0.48 0.66 0.36 0.105 0.146 0.079 190 140 260

2 3 7 0.06 0.04 0.09 0.014 0.010 0.019 1,400 2,100 1,100

Field Corn and Popcorn Field / row crop, tall 0.5 Weeding, Hand 70

12 hr 0.48 0.66 0.36 0.004 0.005 0.003 5,200 3,800 7,000

Scouting 210 0.012 0.016 0.009 1,700 1,300 2,300

1100 0.061 0.084 0.046 330 240 440

2 2 4 0.06 0.11 0.016 0.008 0.014 0.020 2,500 1,500 1,000

Irrigation (hand set) 1900 12 hr 0.48 0.66 0.36 0.105 0.146 0.079 190 140 260

2 3 7 0.06 0.04 0.09 0.014 0.010 0.019 1,400 2,100 1,100

Cotton Field / row crop, low /

medium 0.5 Weeding, Hand 70

12 hr 0.48 0.66 0.36 0.004 0.005 0.003 5,200 3,800 7,000

Scouting 210 0.012 0.016 0.009 1,700 1,300 2,300

Pepper, bell Vegetable, fruiting 0.33 Weeding, Hand 70 0.31 0.44 0.24 0.003 0.004 0.002 7,900 5,700 11,000Dimethoate Human Health Risk Assessment DP No. D416010

Page 68 of 104 Table 11.2.2.4 . Dimethoate Occupational Post

- application Risk Estimates Usin g Chemical

- specific Data (Tomato /MRID 44690302 )

Crop Policy Crop Group

Category Application

Rate (lb ai/A) Activities Transfer

Coefficients (cm 2 /hr ) Time Following

Application (days, unless specified) DFR 1 Dermal Dose (mg/kg/day) 2 MOE 3 (LOC = 100 0 )

Non

- Arid Arid Non

- Arid Arid Non

- Arid Arid Non

- Arid Arid

TOMATO STUDY DATA

PA FL CA PA FL CA PA FL CA PA FL CA

Scouting 210 0.008 0.011 0.006 2,600 1,900 3,500

Transplanting 230 0.008 0.012 0.006 2,400 1,700 3,200

Harvesting, Hand Tying/Training 1100 0.040 0.056 0.030 500 360 670

1 2 2 0.17 0.07 0.16 0.015 0.009 0.020 1,400 2,200 1,000

Irrigation (hand set) 1900 12 hr 0.31 0.44 0.24 0.069 0.096 0.052 290 210 390

2 2 5 0.06 0.07 0.08 0.009 0.016 0.019 2,200 1,300 1,100

Potato Vegetable, "root" 0.5 Weeding, Hand 70

12 hr 0.48 0.66 0.36 0.004 0.005 0.003 5,200 3,800 7,000

Scouting 210 0.012 0.016 0.009 1,700 1,300 2,300

Irrigation (hand set) 1900 0.105 0.146 0.079 190 140 260

2 3 7 0.06 0.04 0.09 0.014 0.010 0.019 1,400 2,100 1,100

Safflower Field / row crop, low /

medium 0.5 Weeding, Hand 70 12 hr 0.48 0.66 0.36 0.004 0.005 0.003 5,200 3,800 7,000

Scouting 1100 0.061 0.084 0.046 330 240 440

2 2 4 0.06 0.11 0.16 0.008 0.014 0.020 2,500 1,500 1,000

Irrigation (hand set) 1900 12 hr 0.48 0.66 0.36 0.105 0.146 0.079 190 140 260

2 3 7 0.06 0.04 0.09 0.014 0.010 0.019 1,400 2,100 1,000

Sorghum, grain Field / row crop, tall 0.5 Weeding, Hand 70

12 hr 0.48 0.66 0.36 0.004 0.005 0.003 5,200 3,800 7,000

Scouting 210 0.012 0.016 0.009 1,700 1,300 2,300

Soybean Field / row crop, low /

medium 0.5 Weeding, Hand 70 0.004 0.005 0.003 5,200 3,800 7,000

Scouting 1100 0.061 0.084 0.046 330 240 440

2 2 4 0.06 0.11 0.16 0.008 0.014 0.020 2,500 1,500 1,000

Tomato Vegetable, fruiting 0.5 Pruning, Hand Weeding, Hand 70 12 hr 0.48 0.66 0.36 0.004 0.005 0.003 5,200 3,800 7,000

Scouting 210 0.012 0.016 0.009 1,700 1,300 2,300Dimethoate Human Health Risk Assessment DP No. D416010

Page 69 of 104 Table 11.2.2.4 . Dimethoate Occupational Post

- application Risk Estimates Usin g Chemical

- specific Data (Tomato /MRID 44690302 )

Crop Policy Crop Group

Category Application

Rate (lb ai/A) Activities Transfer

Coefficients (cm 2 /hr ) Time Following

Application (days, unless specified) DFR 1 Dermal Dose (mg/kg/day) 2 MOE 3 (LOC = 100 0 )

Non

- Arid Arid Non

- Arid Arid Non

- Arid Arid Non

- Arid Arid

TOMATO STUDY DATA

PA FL CA PA FL CA PA FL CA PA FL CA

Transplanting 230 0.013 0.018 0.010 1,600 1,100 2,100

Harvesting, Hand Tying/Training 1100 0.061 0.084 0.046 330 240 440

2 2 4 0.06 0.11 0.16 0.008 0.014 0.020 2,500 1,500 1,000

Irrigation (hand set) 1900 12 hr 0.48 0.66 0.36 0.105 0.146 0.079 190 140 260

2 3 7 0.06 0.04 0.09 0.014 0.010 0.019 1,400 2,100 1,100

Watermelon Vegetable, cucurbit 0.5 Scouting Weeding, Hand Pruning, Hand Thinning Fruit 90

12 hr 0.48 0.66 0.36 0.005 0.007 0.004 4,100 2,900 5,400

Transplanting 230 0.013 0.018 0.010 1,600 1,100 2,100

Harvesting, Hand Turning Harvesting, Mechanically

assisted Training 550 0.030 0.042 0.023 670 480 890

2 1 1 0.06 0.27 0.29 0.011 0.017 0.019 1,800 1,200 1,100

Irrigation (hand set) 1900 12 hr 0.48 0.66 0.36 0.105 0.146 0.079 190 140 260

2 3 7 0.06 0.04 0.09 0.014 0.010 0.019 1,400 2,100 1,100

Wheat ( spring and winter) Field / row crop, low /

medium 0.5 Weeding, Hand 70 12 hr 0.48 0.66 0.36 0.004 0.005 0.003 5,200 3,800 7,000

Scouting 1100 0.061 0.084 0.046 330 240 440

2 2 4 0.06 0.11 0.16 0.008 0.014 0.020 2,500 1,500 1,100

Bold MOE values are below the LOC of 100 0

. 1. DFR = Combined residues of dimethoate and omethoate from a tomato study, adjusted to account for application rate differences and for differences in toxicity of omethoate.

2. Daily Dermal Dose = [DFR (μg/cm 2 ) × Transfer Coefficient × 0.001 mg/μg × 8 hrs/day]  BW ( 69 kg).

3. MOE = POD (20.2 mg/kg/day) / Daily Dermal Dose.Dimethoate Human Health Risk Assessment DP No. D416010

Page 70 of 104 

### Restricted

- Entry Interval (REI)

Current product

- label REIs range from 48 hours to 24 days depending on the crop and location (i.e., arid versus non

- arid areas). Based on the current post

- application dermal exposure assessment (Tables 11 .2.2.2

- 11 .2.2.4), REIs of 12 hours to more than 30 days would be necessary to reach acceptable MOEs (i.e., MOEs ≥ 100 0 ) from exposure to the combined

residues of dimethoate and omethoate. Table 11 .2.2.5 provides a summary of the current REIs on product labels and the REIs based on the quantitative post

- application exposure assessment

for dimethoate that would be needed to achieve risks that were not of concern

.

Even though REIs of 12 and 24 hours are long enough for MOEs to reach the LOC of 100 0 for

some crops/activities, HED recommends a minimum REI of 48 hours (72 hours in arid regions)

to be protective of potential for exposure to omethoate

, which is kn own to form after application.

These REIs are in line with the 40 CFR 156.208 (c) (2) assignments for active ingredients that are classified as Toxicity Category I for acute dermal, eye irritation, and prim ary skin irritat ion.

Table 11.2.2.5 . Summary of Restricted Entry Intervals

Crop Current REI on product labels HED recommended REI

Non

- Arid Arid Non

- Arid Arid
Cherry 10 days 14 days >30 days >30 days

Christmas tree 10 days 14 days 29 days >30 days Forestry 14 days 24 days >30 days >30 days Grapefruit 10 days 14 days 26 days >30 days

Lemon 10 days 14 days 26 days >30 days Orange 10 days 14 days 26 days >30 days

Nursery Crop (Ornamentals,

Non

- bearing Plants) Woody ornamentals 10 days 14 days

29 days ( >30 days if

airblast >1 lb ai/A) >30 days

( >30 days

if airblast

>1 lb ai/A) Herbaceous

ornamentals 48 hours

Conifer seed orchards 48 hours (16 days if airblast >1 lb ai/A) 4 days

(25 days if

airblast >1 lb ai/A)

Pear 10 days 14 days >30 days >30 days

Pecan

48 hours 7 days 10 days

Kale

48 hours 1 7 days Lettuce, leaf

Mustard Green

Swiss Chard
Pea, Green 48 hours 1 6 days Turnip 48 hours 1 7 days

Alfalfa 3 days 7 days Asparagus Bean, dry, and Pea, dry

Broccoli 48 hours 72 hours 4 days 11 days Brussels Sprouts 48 hours 72 hours 4 days 14 days

Cauliflower 48 hours 72 hours 4 days 11 days Celery 48 hours 3 days 7 days

Field Corn and Popcorn 48 hours (4 days for detasseling) 48 hours (15 days

for detasseling) 3 days 7 days

Cotton 48 hours 48 hours 1 72 hours 1Dimethoate Human Health Risk Assessment DP No. D416010

Page 71 of 104 Table 11.2.2.5 . Summary of Restricted Entry Intervals

Crop Current REI on product labels HED recommended REI

Non

- Arid Arid Non

- Arid Arid Forage Crop 48 hours 3 days 7 days Pepper, bell 48 hours 2 days 5 days

Potato 48 hours 3 days 7 days

Safflower 48 hours 3 days 7 days Sorghum, grain 48 hours 48 hours 1 72 hours 1
Soybean 48 hours 48 hours 4 days

Tomato 48 hours 3 days 7 days

Watermelon 48 hours 3 days 7 days Wheat (spring and winter) 48 hours 48 hours 4 days

1. Even though REIs of 12 and 24 hours are long enough for MOEs to reach the LOC of 100 for some crops/activities, HED recommends a minimum REI of 48 hours (72 hours in arid regions) for the product labels to be protective of the acute toxicity of omethoate

.



### 12 .0 References

Dimethoate. Response to Waiver Request on Residue Data Requirements. D357 808, 07

- JAN

- 2010, M. Sahafeyan

.

Dimethoate. Response to Reregistration Requirements: Supplemental Data Pertaining to Characterization of Radioactive Residues in Milk, Radiovalidation of the Livestock Analytical Method, Storage Stability Intervals, Magni tude of Residues for Cotton Gin By

- Product and Alfalfa Grown for Seed, Safflower Processing and an (Unsolicited) Olive Metabolism Study. D232849, 24

- MAY

- 2011, M. Sahafeyan

.

Dimethoate. Response to Deficiency: New Ruminant and Poultry Livestock Feeding Studies; A New Enforcement Method for Livestock Commodities Including a Final Method Validation; Storage Stability of Livestock Tissues; Magnitude of Residues on Grass Grown for Seed. D239886, 12

- NOV

- 2013, M. Sahafeyan

.

Tier II Drinking Water Assessment for Dimethoate for the Use in Human Health Risk Assessment in the Regi stration Review Risk Assessment. D415002, 28

- JUL

- 2014, J. Me léndez.

Bouchard MF, Chevrier J, Harley KG, Kogut K, Vedar M, Calderon N, et al. Prenatal Exposure to Organophosphate Pestici des and IQ in 7

- Year

- Old Children. Environ Health Perspectives. 2011;119:1189

- 1195.

Bouchard M.F., Bellinger D.C., Wright R.O., Weisskopf M.G., (2010). Attention

- Deficit/Hyperactivity Disorder and Urinary Metabolites of Organophosphate Pesticides. PEDIATRICS DOI:10.1542/peds.2009

- 3058.

Chen L, Zhao T, Pan C, Ross JH, Krieger RI. (2012) Preformed biomarkers including dialkylphosphates (DAPs) in produce may confound biomonitoring in pesticide exposure and risk assessment. J Agric Food Chem. 2012 Sep 12;60(36):9342

- 51. doi: 10.1021/jf303116p. Epub 2012 Sep 4.

Engel SM, Berkowitz GS, Barr DB, Teitelbaum SL, Siskind J, Meisel SJ, Wetmur JG, Wolff MS. Prenatal Organophosphate Metabolite and Organochlorine Levels and Performance on the Brazelton Neona tal Behavioral Assessment Scale in a Multiethnic Pregnancy Cohort. American Journal of Epidemiology.
2007;165:1397

- 1404.

Engel SM, Wetmur J, Chen J, Zhu C, Barr DB, Canfield RL, Wolff MS. Prenatal Exposure to Organophosphates, Paraoxonase 1, and Cognitive Development in Childhood. Environmental Health Perspectives. 2011;119:1182

- 1188.Dimethoate Human Health Risk Assessment DP No. D416010

Page 72 of 104 Eskenazi B, Harley K, Bradman A, Weltzien E, Jewell NP, Barr DB, Furlong CE, Holland NT. Association of in Utero Organophosphate Pesticide Exposure and Fetal Growth and Len gth of Gestation in an Agricultural Population. Environmental Health Perspectives. 2004;115:792

– 798.

Eskenazi B, Marks AR, Bradman A, Harley K, Barr DB, Johnson C, Morga N, Jewell NP. Organophosphate Pesticide Exposure and Neurodevelopment in Young Mexica n

- American Children. Environmental Health Perspectives. 2007;115:792

– 798.

FIFRA Scientific Advisory Panel. (2012). Transmittal of the Meeting Minutes from the FIFRA Scientific Advisory Panel Meeting of April 10

- 12, 2012. FIFRA Scientific Advisory Panel, O ffice of Science Coordination and Policy, Office of Prevention, Pesticides and Toxic Substances, U.S. Environmental Protection Agency. Washington, DC. Available: http://www.epa .gov/scipoly/sap/meetings/2012/041012meeting.html

Fortenberry, GZ, Meeker, JD, Sánchez, BN, Barr, DB, Panuwet, P, Bellinger, D, Schnaas, L, Solano

- González, M, Ettingera, AS, Hernandez

- Avila, M, Hu, H, Tellez

- Rojoj, MM. Urinary 3,5,6

- trichloro

- 2

- pyridinol (TCPY) in pregnant women from Mexico City: Distribution, temporal variability, and relationship with child attention and hyperactivity. International Journal of Hygiene and Environmental Health 217 (2014): 405

– 412.

Forsberg ND, Rodriguez

- Proteau R, Mab L , Morréc J, Christensen JM, Maierc CS, Jenkins JJ, Anderson KA. Organophosphorus pesticide degradation product in vitro metabolic stability and time

course uptake and elimination in rats following oral and intravenous dosing. Xenobiotica, 2011; 41(5): 422

– 429.

Furlong, Melissa A., Engel, Stephanie M., Boyd Barr, Dana, Wolff, Mary S. Prenatal exposure to organophosphate pesticides and reciprocal social behavior in childhood. 2014. Environment International 70:125

- 131.

Guodong, Ding, Pei, Wang, Ying, Tian, Jun, Zhang, Yu, Gao, Xiaojin, Wang, Rong, Shi, Guoquan, Wang, and Xiaoming, Shen. Organophosphate Pesticide Exposure and Neurodevelopment in Young Shanghai Children. Environmental Science and Technology 46:2911

- 2917, 2012.

Marks AR, Harley K, Bradman A, Kogut K, Barr DB, Johnson C, et al. Organophosphate Pesticide Exposure and Attention in Young Mexican

- American Children: The CHAMACOS Study. Environmental Health Perspectives. 2010;118:1768

- 1774.

Oulhote, Youssef and Bouchard, Maryse F. Urinar y Metabolites of Organophosphate and Pyrethroid Pesticides and Behavioral Problems in Canadian Children. Environmental Health Perspectives. 121:1378

- 1384 (2013)

Racke J.D. Degradation of organophosphorous insecticidesin environmental matrices. In: Organo phosphates Chemistry, Fate and Effects. Academic Press, Inc., San Diego, CA, 1992, pp 47

– 72.

Rauh VA, Garfinkel R, Perera FP, Andrews HF, Hoepner L, Barr DB, Whitehead R, Tang D, Whyatt RW. Impact of Prenatal Chlorpyrifos Exposure on Neurodevelopment in t he First 3 Years of Life Among Inner

- City Children. Pediatrics. 2006;18(6): 1835

- 1859.

Rauh V, Arunajadai S, Horton M, Perera F, Hoepner L, Barr DB, et al. 2011. Seven

- Year Neurodevelopmental Scores and Prenatal Exposure to Chlorpyrifos, a Common Agricultural Pesticide. Environmental Health Perspectives. 2011;119:1196

- 1201.

Shelton, Janie F., Geraghty, Estella M., Tancredi, Daniel J., Delwiche, Lora D., Schmidt, Rebecca J., Ritz, Beate, Hansen, Robin L., and Hertz

- Picciotto, Irva. Neurodevelopment al disorders and prenatal residential proximity to agricultural pesticides: The CHARGE Study. Environmental Health Perspectives 122:1103

– 1109, 2014.Dimethoate Human Health Risk Assessment DP No. D416010

Page 73 of 104 U.S. Environmental Protection Agency. (2008). Draft Science Issue Paper: Chlorpyrifos Hazard and Dose Res ponse Characterization

. http://www.epa.gov/scipoly/sap/meetings/2008/091608_mtg.htm

U.S. Environmental Protection Agency. (2012). Draft Issue Paper: Scientific Issues Concernin g Health Effects of Chlorpyrifos. http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

- OPP

- 2012

- 0040

- 0002

Young JG, Eskenazi B, Gladstone EA, Bradman A, Pedersen L, Johnson C, Barr DB, Furlong CE, Holland NT. Association Between In Utero Organophosphate Pesticide Exposure and Abnormal Reflexes in Neonates. NeuroToxicology. 2005;26:199

– 209.

Zhang, Ying, Han, Song, Liang, Duohong, Shi, Xinzhu, Wang, Fengzhi, Wei Liu, Zhang, Li, Chen, Lixin, Gu, Yingzi, Tian, Ying. Prenatal exposure to organophosphate pesticides and neurobehavioral development of neonates: A birth cohort study in Shenyang, China. PlosOne 47:80

– 85, 2014.

Zhang X, Driver JH, Li Y, Ross JH, Krieger R I. (2008) Dialkylphosphates (DAPs) in fruits and vegetables may confound biomonitoring in organophosphorus insecticide exposure and risk assessment. J Agric Food Chem. 2008 Nov 26;56(22):10638

- 45. doi: 10.1021/jf8018084.

RDI: RAB1 ( 9/ 15 /2015)

cc: M.M. Perron

M.M. Perron : S1095 5 :PY

- S:(703) 347

- 0395 :7509P:RAB1Dimethoate Human Health Risk Assessment DP No. D416010

Page 74 of 104 

### Appendix A. Toxicology Profile

A.1 Toxicology Data Requirements

Study requirements (40 CFR 158.340) for dimethoate are presented below. Use of the new guideline numbers does not imply that the new (1998) guideline protocols were used.

Study Technical

Required Satisfied

870.1100 Acute Oral Toxicity

................................ ....................... 870.1200 Acute Dermal Toxicity

................................ .................. 870.1300 Acute Inhalation Toxicity

................................ .............. 870.2400 Acute Eye Irritation

................................ ....................... 870.2500 Acute Dermal Irritation

................................ ................. 870.2600 Skin Sensitization

................................ .......................... yes

yes

yes

yes

yes

yes yes

yes

yes

yes

yes

yes
870.3100 90

- Day Oral Toxicity in Rodents

................................ .. 870.3150 90

- Day Oral Toxicity in Nonrodents

............................. 870.3200 21/28

- Day Dermal Toxicity

................................ .......... 870.3250 90

- Day Dermal Toxicity

................................ ............... 870.3465 90

- Day Inhalation Toxicity

................................ ........... yes

yes

yes

no

yes yes

yes

yes

-- yes 1
870.3700a Prenatal Developmental Toxicity (rodent)

.................... 870.3700b Prenatal Developmental Toxicity (nonrodent)

.............. 870.3800 Reproduction and Fertility Effects

................................ yes

yes

yes yes

yes

yes 870.4100a Chronic Toxicity (rodent)

................................ .............. 870.4100b Chronic Toxicity (nonrodent)

................................ ........ 870.4200a Carcinogenicity (rat)

................................ ...................... 870.4200b Carcinogenicity (mouse)

................................ ............... 870.4300 Combined Chronic Toxicity/Carcinogenicity

............... yes

yes

yes

yes

yes yes 2

yes

yes 2

yes

yes 870.5100 Mutagenicity

— Bacterial Reverse Mutation Test

.......... 870.5300 Mutagenicity

— Mammalian Cell Gene Mutation Test

.. 870.5xxx Mutagenicity

— Structural Chromosomal Aberrations

.. 870.5xxx Mutagenicity

— Other Genotoxic Effects

....................... yes

yes

yes

yes yes

yes

yes

yes 870.6100 Acute Delayed Neurotoxicity (hen) 870.6200a Acute Neurotoxicity Screening Battery (rat)

................. 870.6200b 90

- Day Neurotoxicity Screening Battery (rat)

.............. 870.6300 Developmental Neurotoxicity

................................ ....... no

yes

yes

yes --

yes

yes

yes
870.7485 Metabolism and Pharmacokinetics

................................ 870.7600 Dermal Penetration

................................ ........................ 870.7800 Immunotoxicity

................................ ............................. yes

no

yes yes

-- yes

1 An inhalation study with omethoate, which is more potent than dimethoate, is available.

2 The combined chronic toxicity/carcinogenicity study satisfies the requirement of the study.Dimethoate Human Health Risk Assessment DP No. D416010

Page 75 of 104 

### A.2. Toxicity Profiles

Table A.2.1. Acute Toxicity Profile

- Dimethoate

Guideline No. Study Type MRID(s) Results Toxicity Category

870.1100 Acute oral (rat) 48890603 LD50 = 550 mg/kg (F) III

870.1200 Acute dermal (rabbit) 48890604 LD50 > 5000 mg/kg IV

870.1300 Acute inhalation (rat) 48890605 LC50 > 2.1 mg/L IV

870.2400 Acute eye irritation (rabbit) 48890606 Moderate irritant II

870.2500 Acute dermal irritation (rabbit) 48890607 Not a dermal irritant IV

870.2600 Skin sensitization (guinea pig) 48890608 Not a sensitizer N/A

Table A.2.2. Acute Toxicity Profile

- Omethoate

Guideline No. Study Type MRID(s) Results Toxicity Category

870.1100 Acute oral (rat) 46099809 LD50= 22/28 mg/kg (M/F) I

870.1200 Acute dermal (rat) 46099810 LD50= 215 mg/kg I

870.1300 Acute inhalation (rat) 46099813 LC50= 0.28 mg/kg II



### Note: Studies have not been updated to reflect current HED policy. Endpoint selection was driven by BMD modeling of the AChE activity to obtain BMD 10 

### and BMDL 10 

### values. As a result, updates to NOAEL/LOAEL values (or NOEL/LOEL values) in these studies would not ultimately impact current PODs or risk estimates. Consequently, the Agency did not find it necessary to update these studies at this time

.

Table A.2.3. Subchronic, Chronic, and Other Toxicity Profile

- Dimethoate

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

Classification /Doses Results

870.3100 90

- Day Oral

Toxicity in Rodents (rat) 00051675, 0077532

0,2,8,32,50, or 400 ppm (0, 0.1, 0.4, 1.6, 2.5, or 20 mg/kg/d)

Acceptable/guideline Cholinesterase NOEL = 32 ppm (1.6 mg/kg/d)

Cholinesterase LOEL = 50 ppm (2.5 mg/kg/d) based on the depression of plasma, RBC , and brain

cholinesterase

Systemic NOEL = 50 ppm (2.5 mg/kg/d) Systemic LOEL = 400 ppm (20 mg/kg/d ) based on decreased growth and food consumption and increased kidney and liver weight ratios

870.3150 90

- Day Oral

Toxicity in Non

Rodent (dog) 00051676

0, 2, 10, 50, or 1500

- 3000

ppm (0, 0.05, 0.25, 1.25, or

37.5

- 75 mg/kg/d)

Acceptable/Non

- guideline (with chronic dog) Cholinesterase NOEL = 2 ppm (0.05 mg/kg/d)

Cholinesterase LOEL = 10 ppm (0.25 mg/kg/d) based on depression of RBC cholinesterase

Systemic NOEL = 50 ppm (1.25 mg/kg/d) Systemic LOEL = 1500 ppm (37.5 mg/kg/d) bas e d

on tremors and decrease d food consumption in

females

Only 1

- 2 dogs treated per groupDimethoate Human Health Risk Assessment DP No. D416010

Page 76 of 104 Table A.2.3. Subchronic, Chronic, and Other Toxicity Profile

- Dimethoate

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

Classification /Doses Results

870.3200 Dermal Toxicity

(rat)

5

- day exposure (using 43.5% a.i. formulation) 44818902 (1999)

0, 5, 10, 20, 40, or 100 mg/kg/d

Acceptable/non

- guideline Males: NOAEL = 40 mg/kg/d LOAEL = 100 mg/kg/d based on statistically significant inhibition of RBC and brain

cholinesterase activity

Females: NOAEL = 10 mg/kg/d LOAEL = 20 mg/kg/d based on statistically significant inhibition of RBC and brain

cholinesterase activity

870.3200 28

- Day Dermal

Toxicity (rat) 44999101 (1999)

0, 10.5, 21, 31.5, or 63 mg/kg/d

Acceptable/guideline NOAEL = 10.5 mg/kg/d LOAEL = 21 mg/kg/d based on reduced brain

cholinesterase activity (both sexes)

No systemic or dermal toxicity

870.3700a Prenatal

Developmental in Rodent (rat) 00150130 (1984)

0, 3, 6, or 18 mg/kg/d

Acceptable/guideline Maternal NOEL = 3 mg/kg/d Maternal LEL = 6 mg/kg/d based on increased reaction to sounds and touch stimuli, body tremors, and unsteady gate

Developmental NOEL = 18 mg/kg/d Developmental LEL not established

870.3700b Prenatal

Developmental in

Non

- Rodent (rabbit) 00149126, 00159760

(1984) 0, 10, 20 or 40 mg/kg/d

Acceptable/guideline Maternal NOEL = 10 mg/kg/d Maternal LEL = 20 mg/kg/d based on decreased

food consumption and clinical signs

Developmental NOEL = 20 mg/kg/d Developmental LEL = 40 mg/kg/d based on decreased fetal body weight

870.3800 Reproduction and

Fertility Effects (rat) 42251501 (1992)

0, 1, 15, or 65 ppm (0, 0.08, 1.2, or 5.46 mg/kg/d)

Acceptable/guideline Cholinesterase NOEL = 0.08 mg/kg/d

Cholinesterase LEL = 1.2 mg/kg/d based on decreased plasma, erythrocyte and brain

cholinesterase activity

Parental NOEL = 0.08 mg/kg/d Parental LEL = 1.2 mg/kg/d based on decreased

cholinesterase a ctivity in both sexes and generations

Reproductive NOEL = 1.2 mg/kg/d Reproductive LEL= 5.46 mg/kg/d based on decreased fertility index, pup survival and body weightsDimethoate Human Health Risk Assessment DP No. D416010

Page 77 of 104 Table A.2.3. Subchronic, Chronic, and Other Toxicity Profile

- Dimethoate

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

Classification /Doses Results

870.3800 Reproduction and

Fertility Effects (rat) 46181001 (2003)

0, 0.2, 1, or 6.5 mg/kg/d

Acceptable/guideline Parental NOAEL = 0.2 mg/kg/d Parental LOAEL = 1 mg/kg/d based on decreased erythrocyte and brain cholinesterase activity

Offspring NOAEL = 1 mg/kg/d Offspring LOAEL = 6.5 mg/kg/d based on

decreased brain cholinesterase activi ty in females

Developmental NOAEL = 6.5 mg/kg/d Developmental LOAEL = not established

870.3800 Reproduction and

Fertility Effects (rat)

One

- generation range finding 46348201 (1990)

0, 50, 75, or 100 ppm (0, 2.9, 4.4, or 6.1 mg/kg/d in males and 0,
3.9, 5.8, or 7.5 mg/kg/d in females) Parental NOAEL = not established Parental LOAEL = 2.9/3.9 mg/kg/d (M/F) based on decreased plasma, erythrocyte and brain

cholinesterase activity

Offspring NOAEL = not established Offspring LOAEL = 2.9/3.9 mg/kg/d based on

d ecreased plasma, erythrocyte and brain

cholinesterase activity and decreased body weight

870.4100a Chronic Toxicity

(rat ) See 870.4300 See 870.4300

870.4100b Chronic Toxicity

(dog) 41939801, 42192301

(1990) 0, 5, 20, or 125 ppm (0, 0.18, 0.70, or 4.18 mg/kg/d in males and 0,
0.19, 0.76, or 4.31 mg/kg/d in females)

Acceptable/guideline Cholinesterase NOEL = not established

Cholinesterase LEL = 0.18 mg/kg/d based on

decreased brain cholinesterase . Additionally, RBC

cholinesterase decreased in the mid

- an d high

- dose groups and plasma cholinesterase decreased in the high

- dose group.

Systemic NOEL = not established Systemic LEL = 0.18 mg/kg/d based on decreased liver weights in females and presence of a brown, granular pigment in the liver of both sexes.

D ecreased heart weights in the high

- dose group.

870.4200a Carcinogenicity (rat) See 870.4300 See 870.4300

870.4200b Carcinogenicity

(mouse) 00163800 (1986)

0, 25, 100 or 200 ppm (0, 3.75, 15 or 30 mg/kg/d)

Acceptable/guideline Cholinesterase NOEL= not established

Cholinesterase LEL = 3.75 mg/kg/d based on decreased plasma and erythrocyte cholinesterase

. No b rain cholinesterase measurements taken.

Systemic NOEL = not established Systemic LEL = 3.75 mg/kg/d based on

cholinesterase depression in both sexes and hepatocytic vacuolization in female mice

Liver tumors in female mice and lung and hemolymphoreticular system tumors in male mice observed at 30 mg/kg/dDimethoate Human Health Risk Assessment DP No. D416010

Page 78 of 104 Table A.2.3. Subchronic, Chronic, and Other Toxicity Profile

- Dimethoate

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

Classification /Doses Results

870.4300 Combined Chronic

Toxicity/ Carcinogenicity (rat) 00164177 (1986)

0, 1, 5, 25 or 100 ppm (0, 0.05, 0.25, 1.25, or 5 mg/kg/d)

Acceptable/guideline Cholinesterase NOEL = 0.05 mg/kg/d

Cholinesterase LEL = 0.25 mg/kg/d based on

decreased brain and RBC holinesterase activity

Systemic NOEL = 1.25 mg/kg/d Systemic LEL = 5 mg/kg/d based on in creased mortality (females), anemia (males) and increased leukocytes (both sexes)

In males only, dose

- related trends for spleen hemangiosarcomas, spleen hamangiomas/hemangiosarcomas combined, and combined spleen hemagniomas/hemangiosarcomas

and skin heman giosarcomas. Additionally, there were increases in the incidences of spleen hemangioma/hemangiosarcomas combined and of angiogenic tumors at all sites in high dose males.

870.5100 Bacterial reverse

mutation 00063996 (1977)

Acceptable Dimethoate and isodimethoate classified as non

mutagenic

870.5300 In vitro mammalian

cell gene mutation 00151223(1985)

Acceptable Compound

- related increases in mutant frequency ( MF ) were considered equivocal (technical problems with assay and increased MFs did not exceed normal background rates of mutation)

870.5385 In vivo bone marrow

cytogenetics (rat) 00150579 (1985)

Acceptable No clastogenic response up to 150 mg/kg

870.5395 Mammalian

micronucleus (mouse) 00146521 (1985)

Acceptable Did not induce any significant increase in the

number of polychromatic erythrocytes ( PCE ) containing micronuclei with single or multiple doses of 55 mg/kg

870.5450 Dominant Lethal

Assay (mouse) 00150578 (1985)

Acceptable No clastogenic response up to 20 mg/kg/d

870.5500 Unscheduled DNA

synthesis (UDS) in

mammalian cells 43151801 (1990)

Acceptable Positive for inducing UDS in rat hepatocytes exposed to 763.33 ug/ml and above

Positive for inducing UDS in rat hepatocytes exposed to doses up to the highest dose tested of 2290 ug/ml

870.6100 Acute Delayed

Neurotoxicity (hen) 42884401 (1991)

Acceptable/guideline No clinical signs of acute delayed neurotoxicity and

no compound

- related histological changes in nerve

tissueDimethoate Human Health Risk Assessment DP No. D416010

Page 79 of 104 Table A.2.3. Subchronic, Chronic, and Other Toxicity Profile

- Dimethoate

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

Classification /Doses Results

870.6200a Acute Neurotoxicity

Screening Battery (rat) 42865102 (1993)

0, 2, 20, or 200 mg/kg

Acceptable/guideline Systemic NOEL = 20 mg/kg Systemic LEL = 200 mg/kg based on decreased body weight

Neurotoxicity NOEL = 2 mg/kg Neurotoxicity LEL = 20 mg/kg based on pupil

response.

At highest dose tested, additional effects were observed including tremors, decreased motor activity, decreased body temperature, increased catalepsy time and eleven othe r parameters which indicated coordination, sensory and motor systems

were affected

870.6200b Subchronic

Neurotoxicity Screening Battery (rat) 43128201 (1994)

0, 1, 50 or 125 ppm (0, 0.06, 3.22, or 8.13 mg/kg/d for males and 0, 0.08, 3.78 or 9.88 mg/kg/d for females)

Acceptable/guideline Cholinesterase NOEL = 0.06/0.08 mg/kg/d (M/F)

Cholinesterase LOEL = 3.22/3.78 mg/kg/d (M/F)

based on decr e ased cholinesterase activity in the plasma and RBCs . Brain cholinesterase activity reduced at the highest dose tes ted.

870.6300 Developmental

Neurotoxicity (rat) 45529703 (2001)

0, 0.1, 0.5, or 3 mg/kg/d

Acceptable/guideline Maternal NOAEL = 3 mg/kg/d

Maternal LOAEL = not established

Offspring NOAEL = 0.1 mg/kg/d Offspring LOAEL = 0.5 mg/kg/d based on

increased pup death and increased motor activity (horizontal activity)

870.7485 Metabolism and

Pharmacokinetics 43964001 (1995)

Acceptable

- Single oral dose (10 or 100 mg/kg) of 14 C

dimethoate

- Intravenous dose (10 mg/kg) of 14 C

- dimethoate

- 14 day repeated oral

dose of dimethoate followed by single oral

dose of 14 C

- dimethoate No sex

- , dose

- or treatment

- related differences in the absorption, distribution, and elimination of dimethoate. Tmax reached less than 1 hour post

dosing. Total re covery of radioactivity ranged 91

- 97% of the administered dose. Most of the radioactivity was excreted via the urine (85

- 91% of the dose). A small amount of radioactivity was found in feces (1

- 2% of the dose), in the tissues and remaining carcass (1

- 2% o f the dose), and in the expired air as carbon dioxide (2

- 3% of the dose). Dimethoate is metabolized via hydrolytic and oxidative pathways (based on urine analyses). Metabolites include dimethoate carboxylic acid, dimethyldithiophosphate, dimethylthiophosp horic acid, dimethylphosphoric acid, and the oxon analogue, omethoate.

870.7485 Metabolism and

Pharmacokinetics 46497601(2004) A metabolism study with human volunteers was evaluated; however, due to the limitations of the study, including a limited number of subjects and only one dose, it was not useful for dose

- response evaluation and not reliable for risk assessment.Dimethoate Human Health Risk Assessment DP No. D416010

Page 80 of 104 Table A.2.3. Subchronic, Chronic, and Other Toxicity Profile

- Dimethoate

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

Classification /Doses Results

870.7600 Dermal Absorption 43964001 Acceptable 10 or 100 mg/kg Dermal absorption (based on a total amount of radioactivity recovered from urine, tissues, and feces) was 8

- 11% and 1

- 2 % of the administered dose from rats treated at 10 and 100 mg/kg, respectively. No marked sex

- related difference was

observed in the abs orption patterns. The amount of radioactivity recovered from skin wash, extracts from dressing, and treated skin was 62

- 84%, 1.4

- 3.6%, and 2

- 17% of the administered dose, respectively. Total recovery of radioactivity ranged

between 89

- 93% of the administ ered dose for all tested groups within 5 days after dosing.

870.7600 Dermal Absorption 45530501 Acceptable/guideline 0.02, 0.4 and 4.0 mg/cm 2 Results from the high dose not included because excessive amount of applied material found on the application site cover and surrounding skin.

At low

- (0.67 mg/kg) and mid

- dose (13.3 mg/kg) levels, dermal absorption (based on excreta, cage wash, and carcass) was 6% after 1 hr and ranged

from 25

- 38% at 10 and 24 hours.

870.7800 Immunotoxicity 48572807, 48997901 (2011) Acceptable/guideline 0, 5, 25, 75, or 200 ppm (0, 1, 5, 14.2, or 36.4 mg/kg/d) Systemic NOAEL = not established Systemic LOAEL = 1 mg/kg/d based on decreased

brain cholinesterase levels

Immunotoxicity NOAEL = 36.4 mg/kg/d Immunotoxicity LOAEL = not established

Special Studies

Cross

- fostering

Study 46214501 (2004)

Acceptable/non

- guideline 0, 3, or 6 mg/kg/day Maternal NOAEL = not established Maternal LOAEL = 3 mg/kg/day based on clinical

observations of forelimb hair loss and increased incidences of restlessness and scattering of pups

Offspring NOAEL = not established Offspring LOAEL = 3 mg/kg/day based on reduced milk consumption, increased levels of urea in the blood, and increased mortality

Direct pre

- and post

- natal toxicity of the offspring to dimethoate could not be disregarded as significant contributing factors to overall mortality

Comparative

Cholinesterase Study 45529702 (2001)

Acceptable/non

- guideline 0, 0.1, 0.5, or 3.0 mg/kg/d Acute NOAEL = 0.5 mg/kg/day Acute LOAEL = 3.0 mg/kg/day based on decreased blood, RBC and plasma cholinesterase

Repeated NOAEL = 0.1 mg/kg/day Repeated LOAEL = 0.5 mg/kg/day based on

decreased brain cholinesteraseDimethoate Human Health Risk Assessment DP No. D416010

Page 81 of 104 Table A.2.4. Subchronic, Chronic, and Other Toxicity Profile

- Omethoate

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

Classification /Doses Results

870.3200 2 1

- Day Dermal

Toxicity (rat) 46099804 (1979)

Unacceptable 0, 2.5, or 20 mg/kg/day Systemic and dermal NOAEL = 20 mg/kg/day Systemic and dermal LOAEL = not established

Cholinesterase NOAEL = not established

Cholinesterase LOAEL = 2.5 mg/kg/day based on inhibition of brain cholinesterase activity in females

Deficiencies: only 2 dose groups, no dose selection rationale, lack of details regarding substance

pr eparation, age of rabbits and acclimation period not provided, analyses for homogeneity, stability and concentration were not performed, food consumption was not measured, neurological testing and opthalmological exams were not performed,

and lack of measu rements for recommended hematology and clinical chemistry parameters

870.3465 Subchronic

Inhalation Study (rat) 46358601 (1979)

Acceptable/non

- guideline 0, 0.96, 2.3 or 7.5 mg/m 3 NOAEL = not established LOAEL = 0.96 mg/m 3 based on depressed cholinesterase activity in brain (males) and RBCs (both sexes)

870.3700a Prenatal

Developmental in Rodent (rat) 46099806 (1990)

Acceptable/guideline 0, 0.3, 1.0 or 3.0 mg/kg/day Maternal NOAEL = 0.3 mg/kg/day

Maternal LOAEL = 1.0 mg/kg/day based on body weight decrements

Developmental NO AEL = 1.0 mg/kg/d Developmental L OAEL = 3.0 mg/kg/d based on decreased placental weights

870.3700b Prenatal

Developmental in

Non

- Rodent (rabbit) 46099807 (1990)

Acceptable/guideline

0, 0.2, 1.0, or 5.0 mg/kg/day Cholinesterase NOAEL = 0.2 mg/kg/d

Cholinesterase LOAEL = 1 mg/kg/d based on inhibition of RBC and brain cholinesterase activity

Maternal NO A EL = 0.2 mg/kg/d

Maternal L OA EL = 1 mg/kg/d based on body weight decrements

Developmental NO AEL = 0.2 mg/kg/d Developmental L OAEL = 1 mg/kg/d based on increased number of resorptions, increased post

implantation loss and increased incidence of arthrogryposis and epignathusDimethoate Human Health Risk Assessment DP No. D416010

Page 82 of 104 Table A.2.4. Subchronic, Chronic, and Other Toxicity Profile

- Omethoate

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

Classification /Doses Results

870.3800 Reproduction and

Fertility Effects (rat) 46195301 (1981)

Unacceptable
0, 0.05, 0.15, or 0.5 mg/kg/day Parental NO A EL = 0.5 mg/kg/d

Parental L OA EL = not established

Reproductive NO A EL = 0.15 mg/kg/d ay Reproductive L OA EL= 0.5 mg/kg/day based on slight reductions in the gestation indices during the second mating of F 0 and F 1 females

Offspring NOAEL = 0.05 mg/kg/day Offspring LOAEL = 0.15 mg/kg/day based on decreased in body weight and survival indices

870.3800 Reproduction and

Fertility Effects (rat)

Exposure through drinking water 45806201 (1992),

46099802 (1994) Acceptable/guideline 0, 0.5, 3.0, or 18 ppm Parental NOAEL = not established Parental LOAEL = 0.5 ppm based on decreased brain cholinesterase activity

Reproductive NOAEL = 3 ppm Reproductive LOAEL = 18 ppm based on decreased fertility and conceptio n rates, increased precoital interval, decrease in the number of pups/litter and lesions of the epidydymal epithelium (P and F 1 males)

Offspring NOAEL = 3 ppm Offspring LOAEL = 18 ppm based on decreased body weight and reduced survival

870.4100b Chronic Toxicity

(dog) 46099805 (1984)

Supplemental/guideline
0, 0.025, 0.125, or 0.625 mg/kg/day Systemic NOAEL = 0.625 mg/kg/day Systemic LOAEL = not established

Cholinesterase NOAEL = 0.025/0.125 mg/kg/day (M/F)

Cholinesterase LOAEL = 0.125/0.625 mg/kg/day (M/F) based on inhibition of brain and erythrocyte cholinesterase activity

870.4200a Carcinogenicity (rat)

Feeding study 46119402 ( 1979)

Unacceptable
0, 0.015, 0.05, 0.15, or 0.5 mg/kg/day Cholinesterase NOAEL = 0.05 mg/kg/day

Cholinesterase LOAEL = 0.15 mg/kg/day based on inhibition of cholinesterase activity in the brain, erythrocytes and plasma

Systemic NOAEL = 0.5 mg/kg/day Systemic LOAEL = not established

Deficiencies: lack of homogeneity and stability data, weekly clinical examination, eye

examina tions, serum electrolyte measurements, and tabulation of microscopic lesions; animals could have tolerated a higher doseDimethoate Human Health Risk Assessment DP No. D416010

Page 83 of 104 Table A.2.4. Subchronic, Chronic, and Other Toxicity Profile

- Omethoate

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

Classification /Doses Results

870.4200b Carcinogenicity

(mouse)

Exposure through drinking water 46126002 (2001)

Acceptable/guideline 0, 0.5, 4 or 32 ppm (0, 0.10, 0.82, or 6.48 mg/kg/day in males and 0,
0.11, 0.80, 6.61 mg/kg/day in females) Cholinesterase NOAEL = 0.5 ppm

Cholinesterase LOAEL = 4 ppm based on decreased

cholinesterase activity in plasma, erythrocytes, and

brain

Systemic NOAEL = 4 ppm Sy stemic LOAEL = 32 ppm based on tremors in

both sexes

No significant increase in neoplasms

870.4300 Combined Chronic

Toxicity/ Carcinogenicity (rat)

Exposure through drinking water 46126001 (1995)

Acceptable/guideline 0, 0.5, 4 or 32 ppm (0, 0.04, 0.30, or 2.92 mg/kg/day in males and 0,
0.05, 0.44, or 3.93 mg/kg/day in females) Cholinesterase NOAEL = not established

Cholinesterase LOAEL = 0.5 ppm based on inhibition of erythrocyte cholinesterase activity in males. At 4 ppm, brain and erythrocyte activit y decreased in both sexes. Plasma activity decreased at the highest dose tested.

Systemic NOAEL = 4 ppm Systemic LOAEL = 32 ppm based on transient decreases in body weight, clinical signs indicative of neurotoxicity, and lesions in the eyes and

forestoma ch in both sexes; vacuolation of the epididymal epithelium in males; mammary gland hyperplasia in females

870.5100 Mammalian

Activation Gene Mutation Assay 46098604 (1988)

Acceptable/guideline No evidence of induced mutant colonies

870.5300 In vitro mammalian

cell gene mutation 46098612 (1988)

Acceptable/guideline Strong evidence of a concentration related positive response of sister chromatid exchange induced over background; statistically and biologically significant ≥1700 μg/ml

870.5385 In vivo bone marrow

cytogenetics (mice) 46098608 (1988)

Acceptable/guideline No statistically significant increase in frequency of

micronucleated PCE

870.5450 Dominant Lethal

Assay (mouse) 46098605 (1991)

Una cceptable No response up to 20 mg/kg/d

Deficiency: no concurrent positive control data

870.5500 Unscheduled DNA

synthesis in

mammalian cells 46098613 ( 1989)

Acceptable /guideline No evidence of unscheduled DNA synthesis up to 30 mg/kg

870.5550 Unscheduled DNA

synthesis in rat hepatocytes 46098603 (1989)

Acceptable/guideline Evidence of dose related positive response; unscheduled DNA synthesis induced at dose levels ≥256 μg/ml

870.5915 In vivo cytogenetic

mutagenicity 46098607 (1990)

Acceptable/guideline No evidence of sister chromatid exchange ( SCE ) induction up to 20 mg/kg/day

870.6100 Acute Delayed

Neurotoxicity (hen) 46099801(1993)

Acceptable/non

- guideline 140 mg/kg No treatment

- related pathological changes in nerve

tissuesDimethoate Human Health Risk Assessment DP No. D416010

Page 84 of 104 Table A.2.4. Subchronic, Chronic, and Other Toxicity Profile

- Omethoate

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

Classification /Doses Results

870.6200a Acute Neurotoxicity

Screening Battery (rat) 46167701 (2003)

Acceptable/guideline
0, 0.2, 0.25, 0.35, or 5 mg/kg ChE NOAEL = 0.25 mg/kg ChE LOAEL = 0.35 mg/kg

Systemic NOAEL = 0.2 mg/kg Systemic LOAEL = 0.25 mg/kg based on FOB

effects

870.7485 Metabolism and

Pharmacokinetics 46099808

M ale and female rats exhibited signs of toxicity at

0.5

- 4 hrs post

- dosing including trembling, salivation, high breathing rate, and congestion of the eyes. Overall recovery of administered radioactivity

was 88

- 98%. There were no remarkable sex

- , dose

or treatment

- related dif

ferences in the absorption, distribution, and elimination of omethoate. Absorption rates were rapid and T

max was reached within 1 hour post

- dosing. Omethoate was rapidly excreted within 48 hours with the majority excreted via the urine (85

- 97% of the adm inistered dose). The remainder of the administered radioactivity was excreted via the feces (2

- 4% of the administered dose). Biliary excretion was found to account for the majority of the fecal metabolite content. Based upon tissue burden data, omethoat e and/or its metabolites do not appear to undergo any significant sequestration. Omethoate appeared to be metabolized to a greater extent in males than in

females

.

Special Studies

Investigation of

Effects on Long

Term Cholinesterase Activity

Exposure through drinking water for

32 weeks 46099816 (1994)

Acceptable/non

- guideline 0, 100 or 300 ppb Designed to determine a drinking water dose that would result in no inhibition of RBC, plasma or brain cholinesterase activity in young adult rats. No

cholinest erase inhibition was observed in any examined compartment for all doses.

Cholinesterase Activity (dog)

Gavage for 13

weeks 46099814 (1991)

Acceptable/non

- guideline 0 or 0.0125 mg/kg/day No inhibition of cholinesterase activity

In vivo mammalian gene mutation

– spot
test in mice 46098606 (1990)

Acceptable/non

- guideline 0, 4, 8, or 16 mg/kg/day Statistically significant, dose

- dependent increase in number of relevant F1 coat spots in dose groupsDimethoate Human Health Risk Assessment DP No. D416010

Page 85 of 104 Table A.2.4. Subchronic, Chronic, and Other Toxicity Profile

- Omethoate

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

Classification /Doses Results

Acute Comparative

Cholinesterase
Assay 48779401 (2012)

0, 0.1, 0.3, 0.6, or 0.9
mg/kg NOAEL for RBC cholinesterase inhibition=0.1
mg/kg

LOAEL for RBC cholinesterase inhibition=0.3
mg/kg

NOAEL for brain cholinesterase inhibition = 0.1
mg/kg

LOAEL for brain cholinesterase inhibition = 0.3
mg/kg



### Appendix B. Summary of OPP’s Cholinesterase Policy & Use of BMD Modeling

OPP’s cholinesterase (ChE) policy (USEPA, 2000 18 

### ) describes the manner in which ChE data are used in human health risk assessment. The following text provides a brief summary of that document to provide context to points of departure selected.

AChE inhibition can be inhibited in the central or perip heral nervous tissue. Measurements of AChE or ChE inhibition in peripheral tissues (e.g., liver, diaphragm, heart, lung

, etc.) are rare. As such, experimental laboratory studies generally measure brain (central) and blood (plasma and RBC) ChE. Blood mea sures do not represent the target tissue, per se , but are instead used as surrogate measures for peripheral toxicity in studies with laboratory animals or for peripheral and/or central toxicity in humans. In addition, RBC measures represent AChE, whereas plasma measures are predominately butyryl

- ChE (BuChE). Thus, RBC AChE data may provide a better representation of the inhibition in target tissues. As part of the dose response assessment, evaluations of neurobehavior and clinical signs are performed to consider the dose response linkage between AChE inhibition and apical outcomes.

Refinements to OPP’s use of ChE data have come in the implementation of BMD approaches in dose response assessment. Beginning with the OP CRA, OPP has increased its use of BM D modeling to derive P O Ds for AChE inhibiting compounds. Most often the decreasing exponential empirical model has been used.

OPP does have not a defined BMR for OPs. However, the 10% level has been used in the majority of dose response analyses cond ucted to date. This 10% level represents a 10% reduction in AChE activity (i.e., inhibition) compared to background (i.e., controls). Specifically, the BMD 10 

### is the estimated dose where ChE is inhibited by 10% compared to background. The BMDL 10 

### is the l ower confidence bound on the BMD 10



### .

18 USEPA (2000) Office of Pestici de Programs, US Environmental Protection Agency, Washington DC 20460. August 18, 2000 Office of Pesticide Programs Science Policy of The Use of Data on Cholinesterase Inhibition for Risk Assessments of Organophosphorous and Carbamate Pesticides.Dimethoate Human Health Risk Assessment DP No. D416010

Page 86 of 104 

### The use of the 10% BMR is derived from a combination of statistical and biological considerations. A power analysis was conducted by ORD on over 100 brain AChE datasets across more than 25 OPs as part of the OP CRA ( USEPA, 2002). This analysis demonstrated that 10% is a level that can be reliably measured in the majority of rat toxicity studies. In addition, the 10% level is generally at or near the limit of sensitivity for discerning a statistically significant dec rease in ChE activity in the brain compartment and is a response level close to the background brain ChE level. With respect to biological considerations, a change in 10% brain AChE inhibition is protective for downstream clinical signs and apical neuroto xic outcomes. With respect to RBC AChE inhibition, these data tend to be more variable than brain AChE data. OPP begins its BMD analyses using the 10% BMR for RBC AChE inhibition but BMRs up to

20% could be considered on a case

- by

- case basis as long as s uch P O Ds are protective for brain AChE inhibition, potential peripheral inhibition, and clinical signs of neurotoxicity.Dimethoate Human Health Risk Assessment DP No. D416010

Page 87 of 104 

### Appendix C. Summary Tables of Benchmark Dose (BMD) Analyses in Rat Toxicity

Studies

New studies or studies used as points of depart ure were analyzed using the most recent version of EPA’s Benchmark Dose Software (Version 2.4). Results and technical details for these analyses can be found in the latest BMD analysis memo ( M. Perron; 15

- SEP

- 2015; TXR#

0057249 ). All other results were o btained using previous versions of the modeling software and reported in previous risk assessments.

Table C.1. Summary of BMD Results Following Acute Exposures to Dimethoate

.

Study Age Compartment Males Females

BMD 10 (mg/kg/day) BMDL 10

(mg/kg/day) BMD 10

(mg/kg/day) BMDL 10

(mg/kg/day)

Comparative

Cholinesterase Assay (MRID 48779401 ) Adult Brain 2.52 1.74 2.2 1.3

Offspring (PND11) Brain 1.77 1.47 1.55 0.91

Table C.2. Summary of BMD Results Following Acute Exposures to Omethoate

.

Study Age Compartment Males Females

BMD 10 (mg/kg/day) BMDL 10

(mg/kg/day) BMD 10

(mg/kg/day) BMDL 10

(mg/kg/day)

Comparative

Cholinesterase Assay (MRID 45529702 ) Adult Brain 0.15 0.12 0.25 0.20 Offspring (PND11) Brain 0.16 0.14 0.16 0.15

Adult RBC 0.19 0.16 0.22 0.14

Offspring (PND11) RBC 0.13 0.11 0.14 0.13

Acute Neurotoxicity Study (MRID 46167701) Adult Brain 0.26 0.17 0.18 0.11

Table C.3. Summary of BMD Results Following Repeated Exposures to Dimethoate

.

Study Age Compartment Males Females

BMD 10 (mg/kg/day) BMDL 10

(mg/kg/day) BMD 10

(mg/kg/day) BMDL 10

(mg/kg/day)

Comparative

Cholinesterase Assay (MRID 48779401 ) Fetal (GD20) Brain N/A N/A 0.89 0.70
Dams (GD20) Brain N/A N/A 0.34 0.28
Offspring (PND4) Brain NF NF NF NF
Offspring (D21) Brain 0.39 0.32 0.54 0.44
Adult (D11) Brain 0.49 0.37 0.37 0.27

28

- day Rat Oral Toxicity Study (MRID 46288001) Adult Brain 1.0 0.8 0.8 a 0.7 a

DNT Range

Finding (MRID 45529701) Dams (GD20) Brain N/A N/A 0.2 0.2

Fetus (GD20) Brain 1.0 0.3 1.0 0.4

Offspring (PND21) Brain 0.4 0.3 0.5 0.4

Two

- generation Reproduction Toxicity Study (MRID 42251501) Adult

(P generation; day 224) Brain 0.7 0.7 0.3 0.3

Adult (F 1 generation; day 308) Brain 0.4 0.3 0.4 0.3

Two

- generation Reproduction Adult

(P generation; day 205) Brain 0.3 0.2 0.5 0.3Dimethoate Human Health Risk Assessment DP No. D416010

Page 88 of 104 Table C.3. Summary of BMD Results Following Repeated Exposures to Dimethoate

.

Study Age Compartment Males Females

BMD 10 (mg/kg/day) BMDL 10

(mg/kg/day) BMD 10

(mg/kg/day) BMDL 10

(mg/kg/day) Toxicity Study (MRID 46181001) Adult

(F 1 generation; day 218) Brain 0.8 0.4 0.6 a 0.5 a

One

- generation Reproduction Toxicity Study (MRID 46348201) Adult

(P generation; day 91) Brain 0.4 0.3 0.5 0.4

Adult (F 1 generation; day 42) Brain 0.3 a 0.2 a 0.4 0.3

Chronic Oral Toxicity Study (MRID 00164177) Adult Brain 0.25 b 0.22 b

- -

Dermal Toxicity Study (MRID 44999101) Adult Brain 31.3 24.8 28.5 20.2

N/A = not applicable; NF = no reliable fit

.

a Noted as having a poor model fit

. b Value calculated using both sexes and all time points from the chronic oral toxicity study for the OP CRA (2002, 2006)

.

Table C.4. Summary of BMD Results Following Repeated Exposures to Omethoate

.

Study Age Compartment Males Females

BM D 10 (mg/ m 3 /day) BM D L 10

(mg/ m 3 /day) BM D 10

(mg/ m 3 /day) BM D L 10

(mg/ m 3 /day)

Omethoate Inhalation Toxicity Study (MRID 46358601) Adult Brain 0.51 0.38 1.24 1.05Dimethoate Human Health Risk Assessment DP No. D416010

Page 89 of 104 

### Appendix D. Tolerance Summary for Dimethoate

Table D .1. Tolerance Summary for Dimethoate (40 CFR §180.204).

Commodity Established

Tolerance (ppm) HED

Recommended Tolerance (ppm) Comments

(a) General.
Alfalfa, forage 2.0 2.0
Alfalfa, hay 2.0 2.0

Alfalfa, seed

- 4.0 Recommended in Memo M. Sahafeyan D232849;

24

- MAY

- 2011
Bean, dry, seed 2.0 2.0

Bean, lima 2.0 2.0 Bean, lima, succulent
Bean, snap, succulent 2.0 2.0
Blueberry 1 1.0 1.0

Broccoli 2.0 2.0

Cattle, meat byproducts 0.02 0. 1 0 Recommended in Memo M. Sahafeyan D232849;

24

- MAY

- 2011

Cauliflower 2.0 2.0
Celery 2.0 2.0

Citrus, dried pulp 5.0 5.0
Corn, field, forage 1.0 1.0
Corn, field, grain 0.1 0.10

Corn, field, stover 1.0 1.0
Corn, pop, grain 0.1 0.10
Corn, pop, stover 1.0 1.0
Corn, sweet, forage 1.0

- Revoke

- no registered use on sweet corn

Cotton, undelinted seed 0.1 0.10

Cotton, gin byproducts

- 4.0 Recommended in Memo M. Sahafeyan D232849;

24

- MAY

- 2011

Egg 0.02

- Revocation r ecommended in Memo M. Sahafeyan
D232849; 24

- MAY

- 2011

Endive 2.0 2.0

Fruit, citrus, group 10

- 10

- 2.0 Crop group tolerance is being established rather

than individual tolerances

Goat, meat byproducts 0.02 0. 1 0 Recommended in Memo M. Sahafeyan D232849;

24

- MAY

- 2011

Grapefruit 2.0

- Delete individual commodities and establish group

10

- 10 tolerance
Hog, meat byproducts 0.02 0. 1 0 Recommended in Memo M. Sahafeyan D232849;

24

- MAY

- 2011 Horse, meat byproducts 0.02 0. 1 0

Kale 2.0 2.0

Lemon 2.0

- Delete individual commodities and establish group

10

- 10 tolerance

Lettuce, leaf 2.0 2.0

Melon 1.0 1.0

Milk 0.002 0.002Dimethoate Human Health Risk Assessment DP No. D416010

Page 90 of 104 Table D .1. Tolerance Summary for Dimethoate (40 CFR §180.204).

Commodity Established

Tolerance (ppm) HED

Recommended Tolerance (ppm) Comments

Mustard greens 2.0 2.0

Orange 2.0

- Delete individual commodities and establish group

10

- 10 tolerance

Pea 2.0 2.0

Pear 2.0 2.0

Pecan 0.1 0.10

Pepper 2.0 2.0

Potato 0.2 0.20

Poultry, meat byproducts 0.02

- Revocation r ecommended in Memo M. Sahafeyan
D232849; 24

- MAY

- 2011

Safflower, seed 0.1 0.10

Sheep, meat byproducts 0.02 0. 1 0 Recommended in Memo M. Sahafeyan D232849;

24

- MAY

- 2011
Sorghum, grain, forage 0.1 0.10
Sorghum, grain, grain 0.1 0.10
Sorghum, grain, stover 0.1 0.10
Soybean, forage 2.0 2.0
Soybean, hay 2.0 2.0
Soybean, seed 0.05 0.05

Swiss chard 2.0 2.0

Tangerine 2.0

- D elete individual commodities and establish group

10

- 10 tolerance

Tomato 2.0 2.0
Turnip, roots 0.2 0.20
Turnip, tops 2.0 2.0
Wheat, grain 0.04 0.05 Harmonize with Codex MRL
Wheat, hay 2.0 2.0

Wheat, straw 2.0 2.0
Wheat, forage 2.0 2.0

(c) Tolerances with regional registrations.
Asparagus 0.15 0.15
Brussels sprouts 5.0 5.0
Cherry, sweet 2.0 2.0
Cherry, tart 2.0 2.0
Grass, forage

- 0.05 Recommended in Memo M. Sahafeyan D239886;

12

- NOV

- 2013 Grass, hay

- 0.05

1 There are no U.S. registrations as of August 16, 1996.Dimethoate Human Health Risk Assessment DP No. D416010

Page 91 of 104 

### Appendix E . Physical/Chemical Properties

Table E. 1. Physical/Chemical Properties of Dimethoate.

Parameter Value Reference

Molecular Weight 229.25 g mol

pH 3.39 MRID# 48696601

Water solubility (25°C) 39.8 g/L MRID# 48696601

Solvent solubility (25°C) 140 g/100 m L acetone 140 g/100 m

L acetonitrile 120 g/100 m

L cyclohexanone 0.043 g/100 m L dodecane 150 g/100 m

L ethanol 120 g/100 m

L ethyl acetate 0.030 g/100 m L hexane 120 g/100 m

L 2

- propanol 160 g/100 m

L methanol 150 g/100 m

L dichloromethane 52 g/100 m L 1

- octanol 100 g/100 m

L toluene 31 g/100 m L xylenes 120 g/100 m

L 1,2

- dichloroethane 0.024 g/100 m L n

- heptane http://www.fao.org/fileadmin/templ ates/agphome/documents/Pests_Pest

icides/JMPR/Evaluation98/dimetho.

PDF

Vapor pressure (25°C) 1.85 x 10

- 6 mPa MRID# 48696601

Octanol/water partition coefficient, log K OW 0.70 MRID# 48696601

UV/Vis absorption The mean molar absorption coefficient and mean bandwidth for pH 7.10 (at 203.0 ± 0.0 nm) were determined to

be 7661 L/mol

- cm and 16.5 nm. MRID# 47622901Dimethoate Human Health Risk Assessment DP No. D416010

Page 92 of 104 

### Appendix F . Use Summary for Dimethoate

Table F .1. Summary of Registered Labels for Dimethoate

. Product N a me/Formulation Regi s tr a tion No

Gowan Dimethoate E267 10163

- 56

Drexel Dimethoate 4EC 19713

- 231

Drexel Dimethoate 2.67 19713

- 232

Dimethoate 400 34704

- 207

Dimethoate 2.67 EC 34704

- 489

Dimethoate 4E 66330

- 223

Dimethoate 25 WP 66330

- 237

Dimethoate 2.67 EC 66330

- 244
Cymate 267 66330

- 245

Dimethoate 400 67760

- 118

Dimethoate 4E 67760

- 44
Agrisolutions Dimate 4E 9779

- 273
Clean Crop Dimethoate 400 CA970003

Dimethoate 4E ID110008

Dimethoate 400 ID120004 Clean Crop Dimethoate 400 ID980006
Dimethoate 400 OR050019Dimethoate Human Health Risk Assessment DP No. D416010

Page 93 of 104 Table F .2. Summary of Use Directions for Dimethoate.

Crop Applic. Timing,

Type, and Equip. Formulation Maximum Applic

. Rate Max

Seasonal Applic

. Rate RTI

(days) Max No.

Apps per

Season REI PHI (days)

Agricultural

uncultivated areas (Noncropland adjacent to vineyards) Groundboom/

Handgun application Liquid 2 lb ai/A

0.0025 lb ai/gal (Mech HG) NS NS 2 per year NS NS

Alfalfa (field and seed crop) Aerial,

Groundboom, Chemigation Liquid 0.5 lb ai/A 0.5 lb ai/A NS

30 1 per crop

cycle or cutting; 3

per year 48 hours 10

Asparagus Aerial,

Groundboom, Chemigation Liquid 0.5 lb ai/A 1 lb ai/A NS

14 2 48 hours 180

Beans (fresh, snap, lima, dry, not cowpeas) Aerial,

Groundboom, Chemigation (some

labels restrict chemigation) Liquid 0.5 lb ai/A 1 lb ai/A NS

14 2 48 hours NS

0

2

Broccoli,

Cauliflower Aerial,

Groundboom, Chemigation (some

labels restrict chemigation) Liquid 0.5 lb ai/A 1.5 lb ai/A 7 3 48 hours; increased to 72 hours

in outdoor areas where the average annual rainfall is less than 25 inches per year. 7

Brussel sprouts Aerial,

Groundboom, Chemigation (some

labels restrict aerial and chemigation) Liquid 0.5 lb ai/A a 1.5 lb ai/A 7 3 48 hours; increased to 72 hours

in outdoor areas where the

ave ra ge annual rainfall is less than 25 inches per year. 10

Celery Aerial,

Groundboom, Chemigation Liquid 0.5 lb ai/A 1.5 lb ai/A 7 3 48 hours 7

Cherries (preharvest and postharvest) Aerial, Airblast, Chemigation Liquid 1.33 lb ai/A 1.33 lb ai/A NS NS 10 days; increased to 14 days in outdoor areas where the average

annual rainfall is less than 25 inches per year. 21 b

Christmas tree

nurseries Aerial, Airblast,

Chemigation, Handheld; Soil injectors (some

labels restrict aerial and chemigation) Liquid 1 lb ai/A

0.025 lb ai/gal

0.0025 lb ai/gal (Mech HG) 3 lb ai/A 14 3 10 days; increased to 14 days in outdoor areas where the average

annual rainfall is less than 25 inches per year NADimethoate Human Health Risk Assessment DP No. D416010

Page 94 of 104 Table F .2. Summary of Use Directions for Dimethoate.

Crop Applic. Timing,

Type, and Equip. Formulation Maximum Applic

. Rate Max

Seasonal Applic

. Rate RTI

(days) Max No.

Apps per

Season REI PHI (days)

Citrus

- non

- bearing and nursery stock Aerial, Airblast, Chemigation,

Handheld (some

labels restrict aerial and chemigation) Liquid 1 lb ai/A

foliar spray: 0.005 lb ai/gal

0.0025 lb ai/gal (Mech.HG)

soil drench: 2 lb

ai/A 1 lb ai/A NS NS 10 days; increased to 14 days in outdoor areas where the average

annual rainfall is less than 25 inches per y ear NA

Citrus (grapefruit, kumquat, lemons, limes, oranges pummelo, tangelo, and tangerines) Aerial, Airblast,

Chemigation, Handheld (some

labels restrict aerial and chemigation) Liquid 1 lb ai/A 1 lb ai/A NS NS

no more than 2 apps to

mature fruit 10 days; increased to 14 days in

outdoor areas where the average

annual rainfall is less than 25 inches per y ear 15

- 45 (depending on pest)

Corn (field and popcorn) Aerial,

Groundboom, Chemigation (some

labels restrict chemigation) Liquid 0.5 lb ai/A 0.5 lb ai/A NS NS

3 48 hours; 4 days for detasseling

tasks in non

- arid areas and 15 days in outdoor areas where the average annual rainfall is less

than 25 inches per year. 14 c

14 (forage)

14 (grain)

28 (grain)

28 (forage)

42 (grain)

Cotton Aerial,

Groundboom, Chemigation (some

labels restrict chemigation) Liquid 0.5 lb ai/A 1 lb ai/A 14

14 when

water is

used for dilution;

40 when

once refined vegetable

oil is used

for

dilution. 2 48 hours 14Dimethoate Human Health Risk Assessment DP No. D416010

Page 95 of 104 Table F .2. Summary of Use Directions for Dimethoate.

Crop Applic. Timing,

Type, and Equip. Formulation Maximum Applic

. Rate Max

Seasonal Applic

. Rate RTI

(days) Max No.

Apps per

Season REI PHI (days)

Endive, Leaf lettuce, Swiss chard Aerial, Groundboom, Chemigation (some

labels restrict chemigation) Liquid 0.25 lb ai/A 0.75 lb ai/A 7 3 48 hours 14

Garbanzo beans Aerial,

Groundboom, Chemigation Liquid 0.5 lb ai/A 1 lb ai/A 14 2 48 hours 0

2

Grass grown for

seed Aerial,

Groundboom, Chemigation Liquid 0.5 lb ai/A 1 lb ai/A 90 NS 48 hours NS

14

Kale Aerial,

Groundboom, Chemigation (some

labels restrict chemigation) Liquid 0.25 lb ai/A

(Label 66330

- 244: indicates 1.5 pt/A = 0.5 lb ai/A) 0.5 lb ai/A 15 2 48 hours 14

Lentils Aerial,

Groundboom, Chemigation (some

labels restrict chemigation) Liquid 0.5 lb ai/A 1 lb ai/A NS

7 2 48 hours 0

2

14

Lupine Aerial,

Groundboom, Chemigation,

Handheld Liquid 0.5 lb ai/A

0.0025 lb ai/gal (Mech HG) 1 lb ai/A 14 2 48 hours 0

Melons Aerial,

Groundboom, Chemigation (some

labels restrict chemigation) Liquid 0.5 lb ai/A 1 lb ai/A NS

7 NS

2 48 hours 3

Mustard greens Aerial,

Groundboom, Chemigation (some

labels restrict chemigation) Liquid 0.25 lb ai/A 0.5 lb ai/A 9 2 48 hours 14Dimethoate Human Health Risk Assessment DP No. D416010

Page 96 of 104 Table F .2. Summary of Use Directions for Dimethoate.

Crop Applic. Timing,

Type, and Equip. Formulation Maximum Applic

. Rate Max

Seasonal Applic

. Rate RTI

(days) Max No.

Apps per

Season REI PHI (days)

Ornamentals in

outdoor nurseries Aerial, Airblast, Chemigation, Handheld; Soil injectors (some

labels restrict aerial and chemigation) Liquid 4.15 lb ai/A (airblast)

1 lb ai/A

0.08 lb ai/gal

0.0025 lb ai/gal (Mech.HG)

soil drench: 0.06 lb ai/gal and 5.5

lb ai/A

soil injection:

0.004 lb ai/inch of

tree
circumference 4.15 lb ai/A

(airblast only)

3 lb ai/A 14 3 woody ornamentals: 10 days; increased to 14 days in outdoor

areas where the ave rage annual rainfall is less than 25 inches per

year

herbaceous ornamentals: 48

hours

conifer seed orchards: 48 hours (16 days if airblast >1 lb ai/A); increased to 4 days (25 days if airblast >1 lb ai/A) in outdoor areas where the average annual

rainfa ll is less than 25 inches per

year NA

Ornamentals in

outdoor nurseries

(trees grown for pulp

-- forestry) Aerial, Airblast, Chemigation, Handheld; Soil injectors Liquid 2 lb ai/A

0.04 lb ai/gal

0.0025 lb ai/gal (Mech HG)

soil injection:

0.0025 lb ai/inch

tree
circumference 6 lb ai/A NS 3 14 days; increased to 24 days in outdoor areas where the average

annual rainfall is less than 25 inches per year. NA

Pears (including

non

- bearing and nursery stock) Aerial, Airblast,

Chemigation, Handheld (some

labels restrict chemigation) Liquid 1 lb ai/A

0.005 lb ai/gal;

0.0025 lb ai/gal (Mech HG) 1 lb ai/A NS NS 10 days; increased to 14 days in outdoor areas where the average

annual rainfall is less than 25 inches per year 28

Aerial, Airblast WSB 1 lb ai/A 1 lb ai/ADimethoate Human Health Risk Assessment DP No. D416010

Page 97 of 104 Table F .2. Summary of Use Directions for Dimethoate.

Crop Applic. Timing,

Type, and Equip. Formulation Maximum Applic

. Rate Max

Seasonal Applic

. Rate RTI

(days) Max No.

Apps per

Season REI PHI (days)

Peas Aerial,

Groundboom, Chemigation (some

labels restrict chemigation) Liquid 0.16 lb ai/A 0.16 lb ai/A NS

7 NS 48 hours 0

2

Peas (dry; some

labels limit to those in ID, OR and WA only) Aerial,

Groundboom, Chemigation (some

labels restrict chemigation) Liquid 0.33 lb ai/A

0.5 lb ai/A (allowed on SLN) 0.5 lb ai/A NS

7 NS

3 d 48 hours 0

5

- 14 d

Peas (succulent;

some labels limit to those in ID, OR and WA only) Aerial,

Groundboom, Chemigation (some

labels restrict chemigation) Liquid 0.33 lb ai/A

0.5 lb ai/A (allowed on SLN) 0.5 lb ai/A NS

7

14 NS

3 e 48 hours NS

5

- 14 e

Pecans Aerial, Airblast,

Chemigation (some

labels restrict aerial and chemigation) Liquid 0.33 lb ai/A 0.33 lb ai/A NS NS 48 hours 21

Peppers Aerial, Airblast,

Chemigation (some

labels restrict aerial and chemigation) Liquid 0.33 lb ai/A 1.65 lb ai/A 7 5 48 hours NS

0

2 f

Potatoes Aerial, Airblast,

Chemigation (some

labels restrict aerial and chemigation) Liquid

0.5 lb ai/A 1 lb ai/A 7 2 48 hours NS

0

2 g Aerial,

Groundboom WSB

Safflower Aerial, Airblast,

Chemigation (some

labels restrict aerial and chemigation) Liquid 0.5 lb ai/A 0.5 lb ai/A NS

14 NS

1

2 at lower

rate h 48 hours 14 h

Sorghum Aerial, Airblast,

Chemigation (some

labels restrict aerial and chemigation) Liquid 0.5 lb ai/A 1 lb ai/A 7 2 48 hours 28Dimethoate Human Health Risk Assessment DP No. D416010

Page 98 of 104 Table F .2. Summary of Use Directions for Dimethoate.

Crop Applic. Timing,

Type, and Equip. Formulation Maximum Applic

. Rate Max

Seasonal Applic

. Rate RTI

(days) Max No.

Apps per

Season REI PHI (days)

Soybeans Aerial, Airblast,

Chemigation (some

labels restrict aerial and chemigation) Liquid 0.5 lb ai/A 1 lb ai/A 7 2 48 hours 21

28 i

Tomatoes Aerial, Airblast,

Chemigation (some

labels restrict aerial and chemigation) Liquid 0.5 lb ai/A 1 lb ai/A 6 2 48 hours 7

Turnip Aerial, Airblast,

Chemigation (some

labels restrict aerial and chemigation) Liquid 0.25 lb ai/A 1.75 lb ai/A 3 7 48 hours 14

Watermelon Aerial, Airblast,

Chemigation (some

labels restrict aerial and chemigation) Liquid 0.5 lb ai/A 1 lb ai/A 7 2 48 hours 3

Wheat Aerial, Airblast,

Chemigation (some

labels restrict aerial and chemigation) Liquid 0.5 lb ai/A 0.5 lb ai/A NS 2 (at lower rates) 48 hours 35

45

60

a. Label 67760

- 118: directions state max of 0.5 lb ai/A, but also indicate 38.2 fl oz/A = 1 lb ai/A

. b. Label 66330

- 223 lists the PHI as 21 days; but then also says interval b/t last app and harvest is 28 days

.

c. Labels listed various PHIs; not clear if which are correct.

d. Max # apps and PHI listed on SLN

.

e. Max of 3 apps listed on label 67760

- 118; PHI listed on SLNs

.
f. Labels 66330

- 244 and 66330

- 245 list PHI of 2 days

.

g. Labels 66330

- 244 and 66330

- 245 list PHI of 2 days

.
h. A couple of labels (e.g., 34704

- 489) list RTI of 1 4 days and no more than two apps

.
i. One label (67760

- 118) listed a longer PHI

.Dimethoate Human Health Risk Assessment DP No. D416010

Page 99 of 104 

### Appendix G . International Residue Limits

( 035001 ; 09/29/14)

Table G.1. Summary of U.S. Tolerances and International MRLs.

U.S. Canada Mexico 1 Codex 2

Residue Definition:

40CFR180.204 (a) General. Tolerances are established for

total residues of the insecticide dimethoate ( O

, O

- dimethyl S

- ( N

methylcarbamoylmethyl) phosphorodithioate) including its oxygen analog ( O

, O

- dimethyl S

- ( N

methylcarbamoylmethyl) phosphorothioate) O

, O

- dimethyl S

- ( N

methylcarbamoylmethyl) phosphorodithioate, including

the metabolite

omethoate Dimethoate

Commodity Tolerance (ppm)/Maximum Residue Limit (mg/kg) Commodity U.S. Canada Mexico 1 Codex 2

Alfalfa, forage 2.0 Alfalfa, hay 2.0 Bean, dry, seed 2.0

1 beans Bean, lima 2.0 Bean, snap, succulent 2.0 Blueberry 3 1.0 1

Broccoli 2.0 2 Cattle, meat byproducts 0.02 0.05 (*)

Cauliflower 2.0 2 0.2 Celery 2.0 1 0.5 Citrus, dried pulp 5.0 Corn, field, forage 1.0 Corn, field, grain 0.1
Corn, field, stover 1.0 Corn, pop, grain 0.1 Corn, pop, stover 1.0 Corn, sweet, forage 1.0
Cotton, undelinted seed 0.1 Egg 0.02 0.05 (*)

Endive 2.0 Goat, meat byproducts 0.02

Grapefruit 2.0 1.5 citrus fruits 5 citrus fruits (excluding kumquats) Hog, meat byproducts 0.02 Horse, meat byproducts 0.02

Kale 2.0 2

Lemon 2.0 1.5 citrus fruits 5 citrus fruits (excluding kumquats)
Lettuce, leaf 2.0 2 lettuce

Melon 1.0

Milk 0.002 0.05 (*) milk of cattle, goats and sheep Mustard greens 2.0 Orange 2.0 1.5 citrus fruits 5 citrus fruits

Pea 2.0 0.5 1 peas (pods and

succulent=immature seeds)Dimethoate Human Health Risk Assessment DP No. D416010

Page 100 of 104 Table G.1. Summary of U.S. Tolerances and International MRLs.

U.S. Canada Mexico 1 Codex 2

Pear 2.0 2 1

Pecan 0.1

Pepper 2.0 0.5 3 peppers Chili, dried 0.5 peppers, sweet (including pimento or pimiento)

Potato 0.2 0.05 Poultry, meat byproducts 0.02 0.05 (*)
Safflower, seed 0.1 Sheep, meat byproducts 0.02 0.05 (*) Sorghum, grain, forage 0.1 Sorghum, grain, grain 0.1 Sorghum, grain, stover 0.1 Soybean, forage 2.0 Soybean, hay 2.0 Soybean, seed 0.05

Swiss chard 2.0 2

Tangerine 2.0 1.5 citrus fruits 5 citrus fruits (excluding kumquats)

Tomato 2.0 0.5 Turnip, roots 0.2 Turnip, tops 2.0 2 1 turnip greens Wheat, forage 2.0 Wheat, grain 0.04 0.05 Wheat, hay 2.0 Wheat, forage 2.0

Wheat, straw 2.0 1 wheat straw and fodder, dry

MRLs with NO US Equivalent Artichoke, globe 0.05 Barley 2 Cabbage, savoy 2 cabbages 0.05 (*)
Lettuce, head 0.3 Mammalian fats (except milk fats) 0.05 (*)

Mango 1 Po Meat of cattle, goats, horses, pigs and sheep 0.05 (*)

Olives 0.5 Poultry, fats 0.05 (*) Poultry, meat 0.05 (*) Spices, fruits and berries 0.5 Spices, roots and rhizomes 0.1 (*) Spices, seeds 5 Sugar beet 0.05 Turnip, garden Apples 2 Garden beet tops 2 Spinach 2

Strawberries 1

Sunflower seeds 0.1 Completed by: M. Negussie; 10/06/14

1 Mexico defers to US tolerances and/or Codex MRLs for its export purposes.Dimethoate Human Health Risk Assessment DP No. D416010

Page 101 of 104 2 (*) = absent at the limit of quantitation. Po = postharvest treatment, such as treatment of stored grains.

3 There are no U.S. registrations as of August 16, 1996.

(c) Tolerances with regional registrations. Tolerances with regional registration, as defined in §180.1(l), are established for total residues of dimethoate including its oxygen analog in or on the f ollowing food commodities:

Commodity US Canada Mexico 1 Codex 2

Asparagus 0.15 0.05 (*) Brussels sprouts 5.0 0.2 Cherry, sweet 2.0 2 cherries 2 cherries Cherry, tart 2.0Dimethoate Human Health Risk Assessment DP No. D416010

Page 102 of 104 

### Appendix H

– Summary of Surface W ater EDWCs using Maximum and T ypical

A pplication R ates

Table H .1 . Dimethoate EDWCs ( μg/L) for Dimethoate Uses in the U.S. Corr ected for National PCA, Using Maximum Application Rates.

PRZM Scenario (bold font) / Uses Represented App

Method Date of

First Application (DD

- MM) App Rate

kg ai/A (lb ai/A) No. of

Apps. App.

Interval (days) Natl.

PCA EDWCs (μg/L) 1

Acute Chronic Cancer/

Chronic

01_CA wine grapes/ Agricultural

uncultivated areas (CA only) (Noncropland adjacent to vineyards) Ground

boom, handgun

app. 15

- 02 2.13 (1.9) 2 180 0.91 24.7 3.26 1.74

03_MN alfalfa/ Alfalfa, Sainfoin Aerial 20

- 05 0.560 (0.5) 1/CC

3/year 30 0.91 11.0 1.32 0.928

04_CA cole crops/ Broccoli, Cauliflower; Additionally, Brussels sprouts (aerial, some labels allow use only in CA) Aerial 25

- 01 0.560 (0.5) 3 7 0.91 27.3 3.49 1.90

05_CA cole crops/ Brussels sprouts (ground) Ground 18

- 01 0.841 (0.75) 2 7 0.91 43.9 5.66 1.88

06_CA row crops/ Celery Aerial 05

- 03 0.560 (0.5) 3 7 0.91 7.37 1.00 0.606

07_FL cabbage/ Turnip (greens) Aerial 15

- 01 0.281 (0.251) 7 3 0.91 17.5 1.52 0.983

08_CA potato/ Turnip (roots) Aerial 01

- 05 0.281 (0.251) 7 3 0.91 9.19 0.974 0.814

09_WA orchards/ Cherry (only in ID, MT, OR, UT and WA) Aerial 15

- 10 (pre

harvest) 1.51

(1.35) 1 N/A 0.91 6.77 1.06 1.00

10_WA orchards/ Cherry (only in ID, MT, OR, UT and WA) Aerial 15

- 11 (post

harvest) 1.51

(1.35) 1 N/A 0.91 6.77 1.16 1.09

10b_WA

orchards/ Cherry (only in ID, MT, OR, UT and WA) Ground 15

- 11 (post

harvest) 1.51

(1.35) 1 N/A 0.91 3.31 0.586 0.539

20_FL peppers/ Peppers Aerial 20

- 10 0.377 (0.336) 5 7 0.91 40.0 2.52 1.21

21_FL peppers/ Peppers Ground 20

- 10 0.377 (0.336) 5 7 0.91 39.8 2.39 1.03

22_MI beans / Beans (includes dry beans, excludes cowpeas),

Garbanzos (includes chick peas), Lupine Aerial 20

- 07 0.560 (0.5) 2 14 0.91 8.90 0.847 0.578

23_MS Cotton /

Cotton Aerial 20

- 07 0.560 (0.5) 2 14 0.91 13.8 0.865 0.480

24_PA Tomato /

Tomato Aerial 20

- 09 0.560 (0.5) 2 6 0.91 18.1 1.77 0.919Dimethoate Human Health Risk Assessment DP No. D416010

Page 103 of 104 Table H .1 . Dimethoate EDWCs ( μg/L) for Dimethoate Uses in the U.S. Corr ected for National PCA, Using Maximum Application Rates.

PRZM Scenario (bold font) / Uses Represented App

Method Date of

First Application (DD

- MM) App Rate

kg ai/A (lb ai/A) No. of

Apps. App.

Interval (days) Natl.

PCA EDWCs (μg/L) 1

Acute Chronic Cancer/

Chronic

25_CA citrus / Grapefruit, Kumquat, Lemon, Lime, Orange,

Pummelo (shaddock), Tangelo, Tangerine Aerial 01

- 06 1.121 (1) 1 N/A 0.91 5.40 0.389 0.355

26_FL citrus / Same crops as

above Aerial 01

- 06 1.121 (1) 1 N/A 0.91 38.9 1.95 0.659

27_ID potatoes /

Potatoes Aerial 20

- 08 0.560 (0.5) 2 7 0.91 13.7 1.55 1.26

12_OR Xmas

trees/ Douglas fir (seed orchards) (only in OR and WA) Airblast 01

- 06 5.04 (4.5) 1 N/A 1.0 9.46 0.990 0.927

13_CA forestry/ Cottonwood (forest/ shelterbelt) Aerial 01

- 06 2.24 (2) 3 14 1.0 24.8 3.73 3.68

14_OR Xmas

trees/ Hybrid cottonwood/poplar plantations (some

labels allow use in ID, OR and WA) Aerial 01

- 06 2.24 (2) 3 10 1.0 26.7 3.40 3.27

15_CA nursery/ Citrus, non

- bearing and nursery stock (only in CA and AZ) Soil

drench 01

- 06 2.13 (1.9) 1 N/A 1.0 5.13 0.489 0.462

17_OR nursery/ Ornamental woody shrubs and vines;

Ornamental and/or

shade trees Aerial 01

- 06 1.12 (1) 3 14 1.0 20.8 2.44 2.10

18_NJ nursery/

Ornamental
herbaceous plants 2 Soil

drench 01

- 06 7.29 (6.5) 1 N/A 1.0 105 2 7.66 2 3.53

Bolded and shaded values are the highest EDWCs.

1 Concentrations are modified using a national PCA, but not using a TAF. Application rates in kg ai/ha (lb ai/A). EDWCs were rounded to three significant figures.

2 A maximum rate of 6.5 lb ai/A for this use appears to be a label error; therefore, these results are not considered representative.

Table H .2 . Dimethoate EDWCs ( μg/L) for Dimethoate Uses in the U.S. Corrected for Regional PCA, Using Typical Application Rates and Numbers of Applications 1

Scenario (bold font) / Crops/Uses Represented App

Method Date of

First Application (DD

- MM) Aver.

App Rate kg ai/A (lb ai/A) Aver.

Number of Apps App

Interval (days) Reg.

PCA EDWCs (μg/L) 1

Acute Chronic Cancer/

Chronic

03c_MN alfalfa/

Alfalfa Aerial 20

- 05 0.409 (0.365) 1 (1.1) N/A 0.91 3.39 0.345 0.178

04b_CA cole crops/ Broccoli Aerial 25

- 01 0.535 (0.477) 1 (1.3) N/A 0.61 8.97 0.988 0.381

22c _MI beans / Dry beans, peas Aerial 20

- 07 0.405 (0.361) 1 (1.1) N/A 0.81 4.38 0.352 0.162

23c_MS Cotton

/

Cotton Aerial 20

- 07 0.307 (0.274) 1 (1.2) N/A 0.86 5.76 0.305 0.107

24b_PA Tomato /

Tomato Aerial 20

- 09 0.498 (0.444) 1 (1.3) N/A 0.34 1.38 0.132 0.0850

26b_FL citrus / Oranges Aerial 01

- 06 0.546 (0.487) 1 (1.1) N/A 0.41 8.28 0.410 0.129Dimethoate Human Health Risk Assessment DP No. D416010

Page 104 of 104 Table H .2 . Dimethoate EDWCs ( μg/L) for Dimethoate Uses in the U.S. Corrected for Regional PCA, Using Typical Application Rates and Numbers of Applications 1

Scenario (bold font) / Crops/Uses Represented App

Method Date of

First Application (DD

- MM) Aver.

App Rate kg ai/A (lb ai/A) Aver.

Number of Apps App

Interval (days) Reg.

PCA EDWCs (μg/L) 1

Acute Chronic Cancer/

Chronic

27c_ID potatoes /

Potatoes Aerial 20

- 08 0.369 (0.329) 2 (1.6) 7 0.66 5.99 0.673 0.541

27d_ID potatoes /

Potatoes 2 Aerial 20

- 08 0.369 (0.329) 1 (1.6) 2 N/A 0.66 3.41 0.345 0.269

28_IL corn

/ Corn Aerial 10

- 09 0.338 (0.302) 1 (1.1) N/A 0.88 10.1 0.878 0.261

29_KS sorghum

/ Sorghum Aerial 20

- 08 0.298 (0.266) 1 (1.0) N/A 0.87 4.23 0.340 0.152

30_MS soybeans / Soybeans Aerial 01

- 09 0.484 (0.432) 1 (1.0) N/A 0.86 4.37 0.282 0.132

31_OR snap

beans / Lima

beans Aerial 01

- 08 0.546 (0.487) 2 (1.6) 14 0.66 2.26 0.235 0.197

32_ND wheat

/ Spring wheat Aerial 20

- 06 0.273 (0.244) 1 (1.0) N/A 0.91 0.956 0.103 0.0811

33_ND wheat

/

Winter wheat3 Aerial 20

- 06 3 0.340 (0.303) 1 (1.0) N/A 0.91 1.18 0.128 0.101

12b_OR Xmas

trees/ Douglas fir (seed orchards) (only in OR and WA) Airblast 01

- 06 1.121 (1) 1 N/A 1.0 2.10 0.220 0.206

13b_CA forestry/

Cottonwood (forest/ shelterbelt) Aerial 01

- 06 1.121 (1) 1 N/A 1.0 3.97 0.452 0.470

14b_OR Xmas

trees/ Hybrid cottonwood/poplar plantations (some

labels allow use in ID, OR and WA) Aerial 01

- 06 1.121 (1) 1 N/A 1.0 3.97 0.425 0.407

15b_CA nursery/ Citrus, non

bearing and nursery stock (only in CA and AZ) Soil

drench 01

- 06 1.121 (1) 1 N/A 1.0 0.450 0.0429 0.0406

17b_OR nursery/

Ornamental woody shrubs and vines; Ornamental

and/or shade trees Aerial 01

- 06 0.280 (0.25) 1 N/A 1.0 2.06 0.199 0.147

18b_NJ nursery/

Ornamental herbaceous plants Soil

drench 01

- 06 0.272 (0.243) 1 N/A 1.0 3.93 0.286 0.132

Bolded and shaded values are the highest EDWCs.

1 Concentrations are modified using a PCA, but not using a TAF

. Application rates in kg ai/ha (lb ai/A). EDWCs were rounded to three significant figures.

2 For the ID potato scenario, one and two applications were modeled.

3 The ND wheat scenario is set so that crop occurs in the spring; therefore, the application rat e for winter spring was used, but the chemical was set to be applied during the spring instead of the winter.

4 For the non

- agricultural crops, no typical/average use information was available. EFED made certain assumptions which are described in
Memo, J

. Meléndez, 28

- JUL

- 2014; D415002.