UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D

. C. 20460

Date: July 1 0,2014 OFF I C E OF CHEM I CA L SA FE TY

AND POL LU T I ON P R E VENTION

Subject: Dicrotophos

. Occupational and Resident i a l Exposure Assessment for the Registration Review Risk Assessment

PC Code: 035201

Decision No

. : 454409

Petition No

. : NA

Risk Assessment Type: Occupational / Residentia l Exposure Assessment

T XRNo

. :NA

MRIDNo. : 44731001 DP Barcode : 0418109 Registration No. : NA Regulatory Action: Reg Review

Case No

. : 0145

CAS No.: 141-66-2

40 CFR: §180.299

From: Shalu Shelat, Industrial Hygienist '



## . J**t.. ~**  - --;; > Risk Assessment Branch VI

And / / _____/ 

# /L_**~** Alexandra LaMay, Biologist 

### t/l**~ ~~**  1 Matthew Lloyd, Industrial Hygienist ./JIJJ 

### 1 · Risk Assessment Branch VII

. r

### :(~ Health Effects Division

## (75**9 ~** 

Through: ,(Uv Elissa Reaves

, Chief

. '

Risk Assessment Branch IV 

### I

Hea l t h Effects Div i sion (7509P)

To: and

Kelly O ' Rouke

Zaida Figueroa Exposure Science ;Kd

T hurston Morton

Risk Assessment Branch IV

Division (7509P)

Page I of32Introduction

The Pesticide Reevaluation Division (PRD) requested that th e Health Effects Division (HED)

conduct an exposure and risk assessment for the current ly re gistered uses of dicrotophos as part

of the registration review process. Dicrotophos is re gistered for the use of cotton as well as a micro-injection application for ornamental trees. There are currently no registered nonoccupational (residential uses) for dicrotophos.

It is HED policy to use the best availa ble data to assess exposure. Several sources of generic

data were used in thi s assessment as surrogate data in the absence of chemical-specific data, including [Pesticide Handler s Exposure Da tabase Version 1.1 (PHED 1.1 ); the Agricultural

Handler Expos ure Task Force (AHETF) database ; the Agricultural Reentry Task Force (ARTF)
database; the Residential SOPs (modified Turf SOP for Spray Drift)

, other registrant-submitted

s tudi es (MRID 44 731 001) ]

. Some of these data are propri etary, and subject to the data protection provisions of the Federal Insecticide, F un g icide

, and Rodenticide Act (FIFRA).

Note: Th i s memorandum was reviewed by the Exposure Science Advisory Committee (ExpoSAC) on 09/26113.

Page 2 of32Page 3 of 32 Table of Contents

1.0 Executive Summary

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

2.0 Risk Assessment Conclusions and Recommendations

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

2.1 Summary of Risk Estimates

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

2.2 Label Recommendations from Occupational Assessment

................................ ............... 7

2.3 Label Recommendations from Residential Assessment

................................ .................. 7

2.4 Data Deficiencies and Requirements

................................ ................................ ............... 7

3.0 Hazard Characterization

................................ ................................ ................................ ....... 7

4.0 Use Profile

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

5.0 Residential Exposure and Risk Estimates

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

5.1 Residential Risk Estimates for Use in Aggregate Assessment

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

5.2 Spray Drift

................................ ................................ ................................ ...................... 11 5.2.1 Combined Risk Estimates From Lawn Deposition Adjacent to Applications

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

5.3 Residential Bystander Post

- Application Inhalation Exposure

................................ ....... 16

6.0 Occupational Exposure and Risk Estimates

................................ ................................ ...... 16

6.1 Occupational Handler Exposure/Risk Estimates

................................ ............................ 16

6.2 Occupational Post

- application Exposure/Risk Estimates

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

6.2.1 Occupational Post

- application Inhalation Exposure/Risk Estimates

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

6.2.2 Occupational Post

- application Dermal Exposure/Risk Estimates

.......................... 22 Appendix A. Summary of Occupational and Residential Non

- cancer Algorithms

..................... 27Page 4 of 32

1.0 Executive Summary This document presents an occupational and residential exposure and risk assessment for the currently registered uses of dicrotophos. Dicrotophos is registered for use o n cotton as well as a

micro

- injection application for use on ornamental trees. There are currently no registere d non

occupational (residential uses) for dicrotophos.

Use Profile: Dicrotophos is a broad spectrum insecticide . T he only dicrotophos end

- use formulation currently registered is a water

- miscible formulation which may be foliarly applied to established cotton plants or used as a tree injection treatment for ornamental and non

- food producing trees. All the available pr oducts are classified as Restricted Use and may be purchased and used only by certified applicators or persons under their direct supervision. As a Restricted Use pesticide

, the dicrotophos product labels contain substantial protective measures to prevent worker

exposure; (S ections 4.0 and 6.0 provide more information on personal protective equipment )

.

The currently registered application rates for the use on cotton ranges from 0.2 to 0.5 lbs ai/acre via ground and aerial application. The applications a re specified to be conducted by closed system only. T he pre

- har vest intervals (PHI) is 30 days

. Additionally, the micro

- injection use for ornamental trees is applied by closed system and is not to be used on trees which will produce food within the year following treatment.

This assessment addresses exposure and risk associated with the end

- use products for dicrotophos when used as directed by occupational workers. There is a potential for occupational exposure associated with handler activities (i.e., mixing, loading, and applying) as well as with post

- application activities (i.e., re

- entering treated areas). There are no registered

residential uses associated with dicrotophos at this time. There is, however, the potential for

non

- occupational exposu re a s a result of spray drift. A spray drift assessment was conducted for the cotton use application of dicrotophos.

Exposure Duration:

For the organophosphate pesticides, the match between the toxicological endpoint selection and the exposure duration is different than HED’s approach for conventional chemicals. OPs exhibit a phenomenon known as steady state AChE inhibition. After repeat ed exposure at the same dose, 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

duration. The endpoint selection for orga nophosphate pesticides involves a “single day” and “steady state” approach based on an individual chemical’s cholinesterase inhibition. The steady state approach is appropriate for dicrotophos given the toxicological and exposure profile. The “steady sta te” endpoint selection for dicrotophos overlaps with HED’s traditional short

- term exposure duration endpoint selection and is consider health protective for occupational handlers that apply commercially over longer periods of time (i.e., intermediate

- term exposures). S ince chronic exposure is not expected for the registered uses and a cancer assessment was not
conducted.

Hazard Profile :Page 5 of 32

Dicrotophos is a member of the organophosphate (OP) class of pesticides. Like other OPs , the initiating event in the ad verse outcome pathway (AOP), also often called the mode of action (MOA), for dicrotophos involves inhibition of the enzyme acetylcholinesterase (AChE) via phosphorylation of the serine residue at the active site of the enzyme. This inhibition leads to

acc umulation of acetylcholine and ultimately to neurotoxicity in the central and/or peripheral

nervous system . For dicrotophos, AChE inhibition is the most sensitive endpoint in the toxicology database in multiple species, durations, lifestages, and routes

. Dicrotophos as the parent active ingredient is an AChE inhibiting chemical.

Endpoints and points of departure were selected for dermal, inhalation, and incidental oral routes of exposure. For the incidental oral exposure from steady state durations

, a BMDL 1 0 value of

0.03 mg/kg, based on brain ChE inhibition, and the BMD 1 0 of 0.04 mg/kg was selected as the point of departure ( P o D ) for dicrotophos from the OP Cumulative Risk Assessment ( CRA )

. A steady state d ermal PoD was selected from a 28

- day dermal toxicity study in rats based on brain ChE inhibition ( BMDL 10 = 2.1 mg/kg/day ; BMD 10 = 3.3 mg/kg/day )

. The PoD derived from

the 28

- day dermal rat toxicity study can be refined to account for higher skin permeability in rat compared to human skin. Ther efore, the refined dermal dose for human skin to use as the PoD is 9.33 mg/kg/day. A steady state inhalation PoD was selected from a 28

- day inhalation toxicity study (based on brain ChE inhibition ( BMDL 10 = 0.62 μg/L/day or 0.00062 mg/L/d ay ; BMD 10

= 0.67 μg/L/day or 0.00067 mg/L/d ay)

. A total uncertainty factor of 100X is appropriate for dermal, inhalation, and oral routes of exposures [ 10 X for interspecies extr apolation, 10X for intraspecies variation and a 1X FQPA SF 1 ]. D icrotophos is classified a s showing "Suggestive evidence of carcinogenicity, but not sufficient to assess human carcinogenic potential”. Quantitative risk assessment for dicrotophos using the Reference Dose (RfD) approach will adequately account for all chronic toxic effects, incl uding carcinogenicity

.

Residential Exposure/Risk: There are no currently registered non

- occupational (residential) uses for dicrotophos. However, that does not preclude non

- occupational exposure to dicrotophos.

Spray Drift

A quantitative non

- occupational spray drift assessment was conducted for dicrotophos. Adult dermal risk estimates from indirect exposure to dicrotophos related to spray drift result in buffers of 0 feet for groundboom and aerial applications, (i.e., MOEs ≥ 100 at the edge of the field)

. Children’s (1 to <2 year old) dermal and incidental oral risk estimates from indirect exposure to dicrotophos related to spray drift result in buffers of 250 feet for aerial applications and 75 feet for groundboom applications.

Occupational Handler Exp osure: No chemical

- specific handler exposure data were submitted in support of this registration review

assessment ; therefore, HED relied on surrogate data in accordance with standard policies. Default assumptions established by the HED Science Advisory Council for Exposure (ExpoSAC) were used for parameters such as body weight and amount handled. A Total MOE approach was used as a risk metric since the toxicological effects for these exposure routes were

similar

.

1 Applicable for the residential exposure assessmentPage 6 of 32

For mixer/loaders using the label

- defined engineering controls, Total MOEs range from 91 to 560 for aerial and groundboom, respectively. For applicators using the label defined engineering controls, Total MOEs rang e from 530 to 1,000 for aerial and groundboom applicators, respectively. Human flagging for aerial applications of dicrotophos resulted in a Total MOE of

140.

Occupational Post

- application Exposure: HED expects that post

- application dermal exposure will occur since dicrotophos is applied post

emergence as a foliar spray. Chemical

- specific dislodgeable foliar residue ( DFR ) data were available and used for dicrotophos. HED has determined that steady

- state risk estimates are of not of concern (i.e., MOEs > 100) on the day of treatment (i.e., Day 0) for all of the post

application exposure activities. Based on the Agency's current practices, a quantitative occupational post

- application inhalation exposure assessment was not performed for dicrotophos

at thi s time. If new policies or procedures are put into place, the Agency may revisit the need for a quantitative occupational post

- application inhalation exposure assessment for dicrotophos.

The acute toxicity data for dicrotophos show that this chemical is classified as Toxicity Category

II via the dermal route and for eye irritation and Toxicity Category IV for skin irritation potential. It is a strong skin sensitizer. There were no systemic post

- application risk estimates of concern on day 0 for all post

- application activities. T he reentry interval ( REI ) on the currently registered labels (6 days) meets the minimum requirements.

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 Pesticide Handlers Exposure Database Version 1.1 (PHED 1.1) ; the Agricultural Han dler Exposure Task

Force (AHETF) database; the Agricultural Reentry Task Force (ARTF) database; and the Residential SOPs (Turf SOP) 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 Human Studies Review Board. Descriptions of data sources, as well as guidance on their use, can be found at the Agency

website 2

.

2.0 Risk Assessment Conclusion s and Recommendations

2.1 Summary of Risk Estimates

The occupational handler assessment identified one exposure scenario that resulted in a risk estimate of concern (M/L for aerial applications to cotton with a calculated MOE of 91 and an LOC of 100). To tal MOEs for the occupational handler scenarios range from 91 to 1,000 depending on the exposure scenario. Additionally, there are no occupational post

- application risk

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

- exposure

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

- app

- exposure

- data.htmlPage 7 of 3 2

estimates of concern. The occupational post

- application dermal MOEs range from 470 to 16,000 depending on the time (days) after treatment , and incorporated a chemical

- specific DFR study.

A spray drift assessment was completed for the currently registered uses of dicrotophos. The resulting risk estimates do exceed HED’s level of concern (MOEs < 100) for the combined

dermal and incidental oral routes of exposure at the edge of the field. T he spray drift assessment was completed at the maximum single application rate for cotton (0.5 lbs ai/acre) for the aerial and groundboom application methods.

2.2 Label Recommendations from Occupational Assessment

There are no label recommendations for the currently registered occupational uses of dicrotophos.

2.3 Label Recommendations from Residential Assessment

There are no currently registered non

- occupational (residential) uses of dicrotophos.

2.4 Data Deficiencies and Requirements

There are cur rently no outstanding data requirements for dicrotophos.

3 .0 Hazard Characterization

Acute Toxicity

The acute toxicity data for dicrotophos show that dicrotophos has a high acute toxicity category

for acute oral and acute inhalation toxicity (Category I ). It also has a Category II acute dermal toxicity. The data show acute eye irritation (Category II) and is a strong skin sensitizer but it not a dermal irritant (Category IV).

Table 3. 1 Acute Toxicity Profile

- Dicrotophos

Guideline No. Study Type MRID(s) Results Toxicity Category

870.1100 Acute oral (rat) 00261098/

43893901 M/F LD 50 = 11/8

mg/kg I

870.1200 Acute dermal (rat) 00261098 M/F LD 50 = 876/476 mg/kg II

870.1300 Acute inhalation (rat) 46411001 LC 50 > 0.059 mg/L I

870.2400 Acute eye irritation 00261098 Lesions reversed by 14 days II

870.2500 Acute dermal irritation [species] 00261098 No irritation IV

870.2600 Skin sensitization [species] 00261098 Strong sensitizer

--Page 8 of 32

Toxicological PODs Used for Risk Assessment

The database of toxicology studies for dicrotophos is complete and includes developmental studies in rat and rabbit, a reproductive toxicity study, a DNT, and a comparative ChE study with three components (acute, repeated, gestational). Dicrotophos is an OP with a neurotoxic AOP ; neurotoxicity is the most sensitive effect in all species, routes, and lifestages and is being used in deriving PoDs

. OPs exhibit a phenomenon known as steady state AChE inhibition. After repeated exposure at the same dose, th e 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 duration. In general, OPs reach steady state within 2

- 3 weeks but

this ca n vary among OPs. In the case of dicrotophos, pattern of steady state is reached at or near

15 days of exposure. In addition to the consistency across durations, the data across multiple studies (repeat CCA study, gestational data from the DNT, subchroni c neurotoxicity study, and subchronic rat toxicity study) are similar. For the purposes of the occupational and residential risk assessment, only the steady

- state duration is relevant to the exposure scenarios.

The steady

- state incidental oral PoD is selected from the OP CRA (USEPA, 2002 and 2006)

. The oral PoD is based on the BMDL 1 0 value of 0.03 mg/kg, based on brain ChE inhibition and

the BMD 1 0 of 0.04 mg/kg

. For steady state incidental oral exposures, a total uncertainty factor of

100 X was applie d [10 X for interspecies extr apolation, 10X for intraspecies variation and a 1X FQPA SF].

A steady state inhalation PoD was selected from a 28

- day inhalation toxicity study (MRID 48146702) in female rats based on brain ChE inhibition (BMDL 10 = 0.62 μg/L/ day or 0.00062 mg/L/day; BMD 10 = 0.7 μg/L/day or 0.0007 mg/L/day). A human equivalent concentration (HEC) was not generated from this study based on the following conditions: 1) exposure was via gas and not particles thus resulting in an RGDR instead of RDDR; and 2) the effects observed were only systemic (AChE inhibition) without portal of entry effects (e.g., irritation). For steady state inhalation exposures, a total uncertainty factor of 100 X was applied [ 10 X for interspecies extr apolation, 10X for intraspecies variation and a 1X FQPA SF 3 ].

A steady state d ermal PoD was selected from a 28

- day dermal toxicity study (MRID 4 6484501 ) in rats based on brain ChE inhibition ( BMDL 10 = 2.1 mg/kg/day ; BMD 10 = 3.3 mg/kg/day ) in

the fema le rat

. There is one in vivo dermal penetration rat study (MRID 45099501) and one in

vitro human and rat epidermis absorption study (MRID 45099502) for dicrotophos. The 28

- day dermal rat toxicity study (MRID 46484501) includes quality AChE dose response inhibition data and is being relied upon for the dermal risk assessment. Mathematically, the PoD derived from

the 28

- day dermal rat toxicity study has been adjusted to account for greater rat skin permeability (4

- 72 fold) compared to human skin

. Theref ore, the refined dermal dose for human skin to use as the PoD is 9.33 mg/kg/day. A total uncertainty factor of 100X is appropriate for dermal exposures [ 10X for interspecies extrapolation, 10X for intraspecies variation and a 1X FQPA safety factor].

In accordance with the Agency's Draft Cancer Risk Assessment Guidelines (July 2, 1999), dicrotophos is classified as showing "Suggestive evidence of carcinogenicity, but not sufficient to

3 For the relevant non

- occupational exposure assessmentsPage 9 of 32

assess human carcinogenic potential”. Although the mice study showe d that dicrotophos was

associated with evidence of increased tumor incidence for a single tumor type (thyroid) , HED has determined that quantification of risk using a non

- linear approach; i.e., RfD, for dicrotophos will adequately account for all chronic t oxicity, including carcinogenicity, that could result from exposure to dicrotophos.

A summary of the toxicological doses and endpoints for use in the occupational and residential exposure and risk assessment are provided in Table 3.2.

Table 3.2 Summary of Toxicological Doses and Endpoints and Points of Departure for Dicrotophos

Exposure

Scenario Point of Departure (mg/kg/day) Study and Toxicological

Effects

Incidental Oral Steady State BMDL 10 = 0.03 mg/kg/day

UF A = 10 x UF H = 10 x FQPA SF = 1x Subchronic and chronic toxicity studies (OP CRA
2002, 2006; MRID’s 43980201 and 44527802 )

Inhibition of brain ChE in adult rat

Dermal Steady State (21 days and longer) rat BMDL 10 = 2.1 mg/kg/day

UF A = 10 x UF H = 10 x FQPA SF = 1x

Human Adjusted Dermal PoD =

9.33 mg/kg/day 1 BMD 10 = 3.3 mg/kg/day
28

- day dermal toxicity study (MRID 4 6484501 )

in rats

Inhibition of brain ChE in adult rat

.

Inhalation Steady State (21 days and longer) BMDL 10 = 0.000 62 mg/L/d ay (0.162 mg/kg/day)

UF A = 10 x UF H = 10x FQPA SF = 1x BMD 10 = 0.000 7 mg/L/d ay

28

- day inhalation toxicity study (MRID

4 8146702 )

Inhibition of brain ChE in adult rat

.
Cancer (oral, dermal, inhalation) Classification : "Suggestive evidence of carcinogenicity, but not sufficient to assess human carcinogenic potential ”

. 1 Human Adjusted Dermal PoD = (2.1 x 4.44 = 9.33 mg/kg/day )

Absorption

Since the steady

- state dermal and inhalation PODs were based on route

- specific toxicity studies, no absorption factors were necessary to estimate exposure.

Body Weight

The standard body weight for the general population (80 kg) was used for all exposure scenarios covered in this risk assessment since the endpoints selected were not developmental and/or fetal

effects.Page 10 of 32

4 .0 Use Profile

Dicrotophos is a broad spectrum insecticide and is currently registered as a water

- miscible end

use formulation which may be foliarly applied to established cotton plants or used as a tree injection treatment for ornamental and non

- food producing trees. I t is classified as Restricted Use and may be purchased and used only by certified applicators or persons under their direct supervision. As a Restricted Use pesticide, the dicrotophos product labels contain substantial protective measures to prevent worke r exposure; (Sections 4.0 and 6.0 provide more information on personal protective equipment).

Mixers and loaders for dicrotophos products must use closed system engineering controls, and

wear l ong

- sleeved shirt and long pants , chemical

- resistant gloves, and a chemical

- resistant apron. Applicators and flaggers for cotton applications must use either a closed cockpit (for airplanes)

or enclosed cabs

. Handlers/applicators for the micro

- injection product must wear l ong

- sleeved shirt and long pants , c hemical resistant gloves , c hemical

- resistant footwear plus socks , and

p rotective eyewear

.

Table 3.1. Summary of Directions for Use of Dicrotophos

.
Applic. Timing, Type, and Equip. Formulation

[EPA Reg. No.] Applic.

Rate (lb ai/A) Max. No.

Applic. per

Season Max.

Seasonal Applic. Rate (lb ai/A) PHI

(days) Use Directions and

Limitations

Cotton
Early Season (emergence to

pre

- bloom), Apply by air or ground

5481

- 448 0.2 1 0.2 (during this growth period) NS E ngineering controls/closed system only Do not graze livestock on

treated fields

Late Season Use (first

bloom to 30 days prior to harvest), Apply by air or ground 0.5 2 1.0 (during this growth period) 30 E ngineering controls/closed system only The minimum application

interval between applications is 14 days; Do not graze livestock on

treated fields

Apply by air or ground 5481

- 552 0.4 NS 1.0 30 E ngineering controls/closed system only Do not graze livestock in

treated areas or cut treated crops for feed, do not feed gin trash, Apply by air or ground 5481

- 9024 0.4 NS 1.0 30 E ngineering controls/closed system only

Ornamental Trees

Micro

- injection 7946

- 11 NS NS NS NA Closed system only This product is not to be

used on trees which will produce food within the year following treatmentPage 11 of 32

5 .0 Residential Exposure and Risk Estimates

There are currently no registered non

- occupational ( residential ) uses for dicrotophos at this time.

5. 1 Residential Risk Estimates for Use in Aggregate Assessment

D icrotophos is a Restricted Use Pesticide (RUP) and there a re no currently registered non

occupational (residential) uses of dicrotophos. Based on the labeled use pattern and the exposure profile of dicrotophos, there is no recommended residential contribution to the aggregate risk

assessment.

5

. 2 Spray Drift

Off

- target movement of pesticides can occur via many types of pathways and it is governed 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 con tact. They can also deposit on surfaces where contact with residues can eventually lead to exposures ( e.g. , children playing on lawns where residues have deposited next to treated fields). The potential risk estimates from

these residues can be calculate d using drift modeling coupled with methods employed for residential risk assessments for turf products.

The approach to be used for quantitatively incorporating spray drift into risk assessment include s assessing exposures for children (1 to 2 years old) and adults who have contact with turf where residues are assumed to have deposited via spray drift thus resulting in an exposure scenario. Aside from the predicted re sidues available for transfer, the r outes of expo sure and assessment methodology is 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 use d 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 dicrotophos

. In the spray drift scenar io, 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. Exposures

were considered for 50 feet wide lawns where the nearest s ide of the property was directly adjoining the treated field (at field edge) and at varied distances up to 300 feet downwind of a

treated field. Once the deposited residue values were determined, the remainder of the spray

drift assessment was based on th e algorithms and input values specified in the recently revised (2012) Standard Operating Procedures for Residential Risk Assessment (SOPs)

.

A screening approach was developed for situations where specific label guidance for application parameters is n ot available. 4 AgDrift is appropriate for use only when applications are made by aircraft, airblast sprayers, and groundboom sprayers. When AgDrift was developed, a series of screening 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 represent a

4 http://www.agdrift.com/Page 12 of 32

reasonable upper bound level of drift for common application method s in agriculture. 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 no t allowed). Section 5. 2. 1 provides the screening level drift related risk estimates along with additional risk management options if necessary. These drift estimates represent plausible options for pesticide labels

.

5. 2 .1 Combined Risk Estimates from L awn 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. Dicrotophos is used on cotton and can be applied via g roundboom and aerial equipment at a maximum application rate of 0.5 lbs

ai/acre . The recommended drift scenario screening 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.

 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 which will be described in more detail below (e.g., wind vector assumed to be 10 mph in a downwind direction for entire application/drift event). 5

In addition to the screening level spray drift scenarios described above, additional results are provided which represent viable drift reduction technologies (DRTs) 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. Dermal and incidental oral risk estimates for children 1<2 years old were combined because the toxicity endpoint for each rout e of exposure is the inhibition of brain cholinesterase (ChE). The total applicable Level of Concern is 100 so

MOEs < 100 represent risk estimates of concern. Adult dermal risk estimates from indirect exposure to dicrotophos related to spray drift result in buffers of 0 feet for groundboom and aerial applications, (i.e., MOEs ≥ 100 at the edge of the field). Children’s (1<2 year old) dermal and incidental oral risk estimates from indirect exposure to dicrotophos related to spray drift

result in buffers o f 75 feet for groundboom applications and 250 feet for aerial applications based on the screening level scenarios.

Results are presented in Table s 5.2.1.1 and 5.2.1.2 and indicate that the major risk concern is from aerial applications

. Appropriate drif t reduction technologies such as changing the spray type/nozzle configuration to coarser spray applications may result in less drift and reduced risk

5 AgDrift allows for consideration of even finer spray patterns characterized as very fine to fine. However, this

spray pattern wa s not selected as the common screening basis since it is used less commonly for most agriculture. If assessors identify this use pattern it should be used as the screening criteria and deposition values associated with it are provided in Table 1 below. J ustification for including this spray quality should be included in any assessment based on specific label directions for its use.Page 13 of 32

concerns (i.e., higher MOEs) from aerial applications. Similarly, using coarser sprays and lowering boom height for groundboom sprayers reduces risk concerns.Page 14 of 32

Table 5. 2.1.1 Adult Risk Estimates (MOEs) Related to Indirect Exposure to Spray Drift for Dicrotophos for the Dermal Route of Exposure

Crop/Rate Group Spray Type/

Nozzle Configuration Appl

.

Rate (lb ai/A) TTR

(ug/cm2) At

Edge 10

Feet 25

Feet 50

Feet 75

Feet 100

Feet 125

Feet 150

Feet 200

Feet 250

Feet 300

Feet

Cotton

Aerial Fine to Medium

0.5 0.055575 190 240 290 390 510 650 790 920 1,200 1,500 1,800

Medium to

Coarse 240 320 430 610 860 1,100 1,400 1,700 2,400 3,100 3,800

Coarse to Very

Coarse 270 400 610 940 1,300 1,800 2,300 2,800 3,800 5,000 6,200

Very Fine to

Fine 130 150 160 190 220 250 280 320 390 460 520

AT401, M, 10 mph, 37% SD 210 270 350 470 640 830 1,000 1,200 1,600 1,900 2,400

WASP, M, 10 mph, 37% SD 230 290 390 580 790 1,000 1,200 1,500 1,900 2,400 2,800

AT401, C, 10 mph, 25% SD 250 350 500 740 1,100 1,400 1,700 2,100 2,900 3,800 4,500

WASP, C, 10 mph, 25% SD 290 410 590 940 1,300 1,800 2,200 2,800 3,800 5,000 5,500

AT401, VC, 10 mph, 20% SD 280 430 690 1,100 1,600 2,200 2,800 3,600 5,000 6,200 8,300

WASP, VC, 10 mph, 20% SD 360 570 870 1,400 2,000 2,600 3,600 4,100 6,200 7,100 8,300

Groundboom High Boom

Very fine to

Fine 270 530 890 1,400 2,000 2,500 2,900 3,600 4,500 6,200 7,100

Low Boom Very

fine to Fine 590 1,600 2,500 3,800 5,000 6,200 7,100 8,300 9,900 12,000 17,000

High Boom Fine

to
Medium/Coarse 1,000 2,600 3,800 5,500 7,100 8,300 9,900 9,900 12,000 17,000 17,000

Low Boom Fine

to
Medium/Coarse 1,500 4,100 6,200 8,300 9,900 12,000 17,000 17,000 25,000 25,000 25,000Page 15 of 32

Table 5. 2.1.2 Children (1< 2 years old) Risk Estimates (MOEs) Related to Indirect Exposure to Spray Drift for Dicrotophos for the Combined Dermal and Oral Routes of Exposure

Crop/Rate Group Spray Type/

Nozzle Configuration Appl

. Rate

(lb ai/A) TTR

(ug/cm2) At

Edge 10

Feet 25

Feet 50

Feet 75

Feet 100

Feet 125

Feet 150

Feet 200

Feet 250

Feet 300

Feet

Cotton

Aerial Fine to

Medium

0.5 0.055575 13 16 20 26 35 45 54 63 83 100 120

Medium to

Coarse 16 22 30 42 59 77 97 120 160 210 260

Coarse to Very

Coarse 19 27 42 64 92 120 150 190 260 340 430

Very Fine to

Fine 9 10 11 13 15 17 19 22 27 32 36

AT401, M, 10 mph, 37% SD 15 19 24 32 44 57 70 81 110 130 160

WASP, M, 10 mph, 37% SD 16 20 26 40 54 70 85 100 130 160 190

AT401, C, 10 mph, 25% SD 17 24 34 51 72 95 120 140 200 260 310

WASP, C, 10 mph, 25% SD 20 28 41 64 90 120 150 190 260 340 380

AT401, VC, 10 mph, 20% SD 19 30 47 77 110 150 190 240 340 430 570

WASP, VC, 10 mph, 20% SD 25 39 60 95 140 180 240 280 430 490 570

Groundboom High Boom

Very fine to

Fine 18 37 61 97 140 170 200 240 310 430 490

Low Boom Very fine to

Fine 40 110 170 260 340 430 490 570 680 850 1,100

High Boom

Fine to

Medium/Coarse 70 180 260 380 490 570 680 680 850 1,100 1,100

Low Boom

Fine to

Medium/Coarse 100 280 430 570 680 850 1,100 1,100 1,700 1,700 1,700Page 16 of 32

5

. 3 Residential Bystander Post

- Application Inhalation Exposure

Volatilization of pesticides may be a source of post

- application inhalation exposure to individuals nearby pesticide applications. The agency sought expert advice and input on issues related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on
March 2, 2010 6 . T he agency has evaluated the SAP report and has developed a Volatilization Screening Tool and a subsequent Volatilization Screening Analysis 7

. During Registration Review, the agency will utilize this analysis to determine if data (i.e., flux studies, rout e

- specific inhalation toxicological studies) or further analysis is required for dicrotophos

.

6.0 Occupational Exposure and Risk Estimates

6.1 Occupational Handler Exposure/Risk Estimates

HED uses the term handlers to describe those individuals who are involved in the pesticide application process. HED believes that there are distinct job functions or tasks related to applications and exposures can vary depending on the specifics of each task. Job requirements (amount of chemical used in each applicati on), 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.

Based on the anticipated use patterns and current labeling, typ es of equipment and techniques that can potentially be used, occupational handler exposure is expected from the registered uses of dicrotophos . The quantitative exposure/risk assessment developed for occupational handlers is based on the following scenari os:

 Mixer/Loader (aerial and groundboom equipment)

 Applicators (aerial and groundboom equipment)

 Flagger (from aerial spray applications)

The above exposure scenarios best represent the registered use pattern (i.e., cotton applications) for dicrotophos. Chemigation applications are prohibited on the product labels.

Dicrotophos is available as a Restricted Use Product (EPA7946

- 11) for micro

- injection for systemic suppression of certain insects on ornamental trees. HED has no specific data developed

to r epresent tree injection treatment use ; the exposure and risk associated with tree injection uses (occupational handler and/or postapplication exposure) will not be higher than the quantitatively assessed exposure scenarios addressed below.

Occupational Ha ndler Exposure Data and Assumptions

6 http://www.epa.gov/scipoly/SAP/meetings/200 9/120109meeting.html

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

- HQ

- OPP

- 2014

- 0219Page 17 of 32

A series of assumptions and exposure factors served as the basis for completing the occupational handler risk assessments. Each assumption and factor is detailed below on an individual basis.

Application Rate : Product labels indicate that dicrotophos can be used at a maximum single application rate of 0.5 lbs ai/A. See Section 4 for additional information. The occupational handler assessment was completed assuming the single maximum application rate; lower

ap plication rates result in correspondingly higher exposures (i.e., lower risk to handlers).

Unit Exposures : It is the policy of HED to use the best available data to assess handler exposure. Sources of generic handler data, used as surrogate data in the absence of chemical

- specific data, include PHED 1.1, the AHETF database, the Outdoor Residential Exposure Task Force (ORETF) database, or other registrant

- submitted occupational exposure studies. Some of these data are proprietary (e.g., AHETF data), and subject to the data protection provisions of FIFRA. The standard values recommended for use in predicting handler exposure that are used in this assessment, known as “unit exposures”, are outlined in the “Occupational Pesticide Handler Unit Exposure Surro gate Reference Table 8 ”, which, along with additional information on HED policy on use of surrogate data, including descriptions of the various sources, can be found at the Agency website 9

.

Area Treated or Amount Handled : Based on HED ExpoSAC Policy 9.1, the amount treated or handled per day was assumed to be:

 200 acres for mixing/loading groundboom applications and applying via ground equipment on cotton,

 1200 acres for mixing/loading for aerial applications and applying via aircraft on cotton,

and

 350 acres for flagging for aerial application on cotton crops.

Body Weight: The standard body weight for the general population (80 kg) was used for all exposure scenarios covered in this risk assessment since the endpoints selected were not developmental and/or fetal effects.

Absorption F

actors:
Since the steady

- state dermal point of departure P o D was based on a route

- specific toxicity study, no absorption factor was necessary to estimate exposure. In addition, t he P o D was adjusted to account for the higher rat skin permeability compared to human skin

.

A route

- specific inhalation study is available and was used in the assessment; no absorption factor is necessary to the inhalation assessment.

Exposure Duration:

HED typically classifies exposures f rom 1 to 30 days as short

- term and exposures 30 days to six

months as intermediate

- term. Exposure duration is determined by many things, including the exposed population, the use site, the pest pressure triggering the use of the pesticide, and the

cultura l practices surrounding that use site. For the organophosphate pesticides, the match

8 Available: http://www.epa.gov/opp00001/science/handler

- exposure

- table.pdf

9 Available: http://www.epa.gov/pesticides/science/handler

- exposure

- data.htmlPage 18 of 32

between the toxicological endpoint selection and the exposure duration is different than HED’s approach for conventional chemicals. The endpoint selection for organophosp hate pesticides involves a “single day” and “steady state” approach based on an individual chemical’s

cholinesterase inhibition. T he steady state approach is appropriate for dicrotophos given the toxicological and exposure profile. The “steady state” endpo int selection for dicrotophos overlaps 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).

For most agricultural uses, it is reasonable to believe that occupational handlers will not apply the same chemical every day for more than a one

- month time frame; however, there may be a large agribusiness and/or commercial applicators who may apply a pr odu ct over a period of weeks (e.g. completing multiple applications for mult iple clients within a region).

Dicrotophos is a restricted use pesticide intended for broad spectrum application to cotton fields via aerial and ground equipment. The available pr oduct labels indicate that the product can be used in multiple applications per season (early and mid

- season use) with a minimum 14 day retreatment interval. The intended pests are similar in the early and mid

- season uses (boll weevils, spider mites, aphid s, etc.).

Mitigation/Personal Protective Equipment: Estimates of dermal and inhalation exposure were calculated based on the mitigation of agricultural uses from the July, 2006 dicrotophos RED. Specifically, the RED required engineering controls such as closed cabs and closed mixing/loading systems for occupational handlers. All current dicrotophos labels indicate this level of personal protection for occupational handlers.

Occupational Handler Non

- Cancer Exposure and Risk Estimate Equations

Potential daily exposures for occupational handlers were calculated using the following

formulas:

Daily Exposure (mg ai /day) = UE (μg ai / lb ai) * CF * AR (lb ai /A) * AT (A /day) * 1E

- 3 mg/μg

w here: Daily Exposure = Amount (mg ai/day) that is available for d ermal or inhalation absorption,

UE = Unit Exposure (μg ai / lb ai)

, AR = maximum application rate according to label (lb ai /A) , and

AT = daily acres treated (A /day)

.

The daily doses were calculated using the following formula:

Average Daily D ose (mg ai/kg/day) = [Daily Exposure (mg ai/day) * Absorption (%)] Body Weight (kg)

w here: Average Daily Dose = Absorbed dose received from exposure to a pesticide in a given scenario (mg pesticide active ingredient/kg body weight/day), Daily Exposure = Amount (mg ai/day) that is available for dermal or inhalation absorption, Absorption Factor = A measure of the amount of chemical that crosses a biological boundary such as the skin and lungs (%) , andPage 19 of 32

Body Weight = Body weight determined to represent the population of interest in a risk

assessment (kg)

.

Margin of Exposure: Non

- cancer risk estimates for each application handler scenario are calculated using a Margin of Exposure (MOE), which is a ratio of the toxicological endpoint to the daily do se of concern. The daily dermal and inhalation dose received by occupational

handlers were compared to the appropriate POD ( i.e. BMDL 10 ) to assess the risk to occupational handlers for each exposure route. All MOE values were calculated using the followi ng formula:

MOE = POD (typically a BMDL 10 in mg/kg/day) ADD (mg/kg/day)

w here:

MOE = Margin of Exposure: value used by HED to represent risk or risk estimates (unitless),

PO D = Point of Departure,

BMDL10 = Benchmark Dose Level (mg/kg/day): Dose level in a toxicity study, where no observed adverse effects occurred in the study, and

ADD = Average Daily Dose (mg/kg/day) : the absorbed dose received from exposure to a pesticide in a given scenario

.

Combining Exposures/Risk Est imates:

Dermal and inhalation risk estimates were combined in this assessment, since the toxicological effects for these exposure routes were similar. Dermal and inhalation risk estimates were combined using the following formula:

Total MOE = Point of Departure (mg/kg/day) ÷ Combined dermal + inhalation dose (mg/kg/day)

Summary of Occupational Handler Non

- Cancer Exposure and Risk Estimates

Based on the label

- defined protection for occupational handlers (engineering controls), one occupational handler exposure scenario results in a risk estimate of concern (M/L for aerial applications to cotton [0.5 lbs ai/A] ; calculated MOE of 91 with an LOC of 100). The other occupational handler exposure scenarios assessed do not represent risk estimates of concern (i.e., all dermal and inhalation MOEs exceed the LOCs of 100) for the steady

- state exposure

assessment. Combined occupational handler risk estimates are presented using the Total MOE approach. Of the evaluated exposure scenarios, the l owest combined MOE is 91 (LOC =100; M/L for aerial applications to cotton). All the other combined MOEs for occupational handler scenarios range from 140 to 1,000.

In the case of dicrotophos, HED does not have unit exposure data for assessing dermal and

i nhalation exposure for flaggers with engineering controls. HED has presented flagger risk

estimates at baseline PPE (i.e., long

- sleeve shirt, long pants, shoes, socks, no respirator) even though engineering controls for flaggers are required on the registe red product labels

. The proper use of engineering controls significantly decreases handler exposure for this activity.Page 20 of 32

HED has no data to assess exposures to pilots using open cockpits. The only data available is for exposure to pilots in enclosed cockpi ts. Therefore, risks to pilots are assessed using the engineering control (enclosed cockpits) and baseline attire (long

- sleeve shirt, long pants, shoes, and socks); pilots are not required to wear protective gloves. With this level of protection, no

risk estimates of concern for applicators were identified

.

The Agency matches quantitative occupational exposure assessment with appropriate characterization of exposure potential. While HED presents quantitative risk estimates for human flaggers where approp riate, agricultural aviation has changed dramatically over the past two decades. According the 2012 National Agricultural Aviation Association (NAAA) survey of their membership, the use of GPS for swath guidance in agricultural aviation has grown steadily from the mid 1990’s. Over the same time period, the use of human flaggers for aerial pesticide applications has decreased steadily from ~15% in the late 1990’s to only 1% in the most recent (2012) NAAA survey. The Agency will continue to monitor all availa ble information sources to best assess and characterize the exposure potential for human flaggers in agricultural aerial applications.

For mixer/loaders using the label defined engineering controls, Total MOEs range from 91 to

560 for aerial and groundboom, respectively. For applicators using the label defined engineering controls, Total MOEs range from 530 to 1,000 for aerial and groundboom applicators, respectively. Human flagging for aerial applications of di crotophos resulted in a Total MOE of

140.Page 21 of 32

Table 6 .1. 1. Steady

- State Occupational Exposure and Risk Estimates for Dicrotophos

. All estimates are at engineering

controls

.

Exposure Scenario Crop or Target Dermal Unit Exposure (ug/lb ai) 1 Inhalation Unit

Exposure (ug/lb ai) 1 Maximum

Application

Rate 2 Area

Treated or

Amount

Handled Daily 3 Dermal Inhalation Total

Mitigation Level Mitigation Level Dose (mg/kg/day) 4 MOE 5 Dose (mg/kg/day) 6 MOE 7 MOE 8

Mixer/Loader

M/L

- Aerial Application Cotton EC

– 8.6 EC

– 0.083 0.5 1200 A/day 0.0645 140 0.000623 260 91

M/L

- Groundboom Application Cotton EC

– 8.6 EC

– 0.083 0.5 200 A/day 0.0108 860 0.000104 1600 560

Applicator

Aerial Application Cotton EC

– 2.1 EC

– 0.0 049 0.5 1200 A/day 0.0156 600 0.0000368 4400 530

Groundboom Application Cotton EC

– 5.1 EC

– 0.043 0.5 1200 A/day 0.00638 1500 0.0000538 3000 1,000

Flagger

Flagger

- from Aerial Application Cotton Baseline

- 11 Baseline

– 0.35 0.5 350 A/day 0.0241 390 0.000766 210 140

1 PHED/ORETF ( baseline or Eng. Controls [EC] ).

2 Based on registered label ( e.g. Reg. No. # 5481

- 00448 ).

3 Exposure Science Advisory Council Policy #9.1.

4 Dermal Dose = Dermal Unit Exposure (ug/lb ai) x Conversion Factor (0.001 mg/ug) x Application Rate (lb ai/acre or gal) x Area Treated or Amount Handled (A) / BW ( 80 kg).

5 Dermal MOE = Dermal POD ( 9.33 mg/kg/day)/Dermal Dose (mg/kg/day).

6 Inhalation Dose = Inhalation Unit Exposure (ug/lb ai) x Conversion Factor (0.001 mg/ug) x Application Rate (lb ai/acre or gal ) x Area Treated or Amount Handled (A) / BW ( 80 kg).

7 Inhalation MOE = Inhalation BMDL10 ( 0.162 mg/kg/day)/ Inhalation Dose (mg/k g/day).

8 Total MOE = NOAEL (mg/kg/day) ÷ Dermal Dose + Inhalation Dose OR Total MOE = 1 ÷ (1/Dermal MOE + 1/Inhalation MOE).Page 22 of 32

6

. 2 Occupational Post

- application Exposure/Risk Estimates

HED uses the term post

- application to describe exposures that occur when individuals are present in an environment that has been previously treated with a pesticide (also referred to as re

entry exposure). Such exposures may occur when workers enter previously treated areas to perform job functions, i ncluding activities related to crop production, such as scouting for pests or harvesting. Post

- application exposure levels vary over time and depend on such things as the type of activity, the nature of the crop or target that was treated, the type of pes ticide 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.

6.2.1 Occupational Post

- application Inhalati on Exposure/Risk Estimates

There are multiple potential sources of post

- application inhalation exposure to individuals performing post

- application activities in previously 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 Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on March 2, 2010 10 . The Agency has evaluated the SAP report and has developed a Volatilization Screening Tool and a subsequent Volatilization Screening Analysis 11 . During Registration Review, the agency wil l utilize this analysis to determine if data (i.e., flux studies, route

- specific inhalation toxicological studies) or further analysis is required for dicrotophos.

In addition, the Agency is continuing to evaluate the available post

- application inhalation exposure data generated by the Agricultural Reentry Task Force. 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 agency's risk assessments.

Although a quantitative occupational post

- application inhalation exposure assessment was not performed, an inhalation exposure assessment was performed for occupational/commercial handlers. Handler exposure resulting from application of pest icides outdoors is likely to result in higher exposure than post

- application exposure. Therefore, it is expected that these handler inhalation exposure estimates would be protective of most occupational post

- application inhalation exposure scenarios.

6

. 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. Each assumption and factor is detailed below on an individual

basis.

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

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

- HQ

- OPP

- 2014

- 0219.Page 23 of 32

Exposure Duration:

The endpoint selection for organophosphate pesticides involves a “single day” and “steady state” approach based on an individual chemical’s cholineste rase inhibition. T he steady state approach

is appropriate for dicrotophos given the toxicological and exposure profile. The “steady state” endpoint selection for dicrotophos overlaps 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).

Transfer Coefficients : It is the policy of HED to use the best available data to assess post

application exposure. Sou rces of generic post

- application data, used as surrogate data in the

absence of chemical

- specific data, are derived from ARTF exposure monitoring studies, and, as proprietary data, are subject to the data protection provisions of FIFRA. The standard value s recommended for use in predicting post

- application exposure that are used in this assessment, known as “transfer coefficients”, are presented in the ExpoSAC Policy 3 12 ” which, along with additional information about the ARTF data, can be found at the Age ncy website 13

.

Table 6.2.2

. 1: Anticipated Post

- Application Activities and Dermal Transfer Coefficients.

Crops Policy Crop Group Category Transfer

Coefficients Activities

cm 2 /hr

Cotton Field/ Row Crop, Low/Medium 0 Irrigation, Mechanical Weeding

70 Hand Weeding

210 Scouting

Application Rate: The application rates for dicrotophos on the available product labels range from 0.2 to 0.5 lbs ai/A, depending on the target pest. The occupational post

- application assessment was conducted

at the maximum single application rate (0.5 lbs ai/A).

Body Weig ht:

The standard body weight for the general population (80 kg) was used for all exposure scenarios covered in this risk assessment since the endpoints selected were not developmental and/or fetal

effects.

Absorption F

actor :

Since the steady

- state dermal POD was based on a route

- specific toxicity study, no absorption

factor was necessary to estimate exposure

. The POD was adjusted to account for the higher rat skin permeability compared to human skin, however.

12 Available: http://www.epa.gov/pesticides/scie nce/exposac_policy3.pdf

13 Available: http://www.epa.gov/pesticides/science/post

- app

- exposure

- data.htmlPage 24 of 32

Exposure Time:

The av erage occupational workday is assumed to be 8 hours.

Dislodgeable Foliar Residues :

Chemical specific dislodgeable foliar residue (DFR) data have been submitted for dicrotophos

use on cotton (see MRID 44731001) . At two test sites (Mississippi and Texa s) , two applications

of Bidrin ® 8, an emulsifiable concentrate formulation containing 84.2% active ingredient (E isomer), dicrotophos (8 lb ai/gal), were made to cotton foliage at the target rate of 0.5 lb ai/A/application for a total seasonal rate of 1.0 lb ai/A. At all sites, the highest average dicrotophos DFR value occurred immediately aft er the first application and dropped to below the LOQ by 14 days after application . The highest average DFR values (and percent of application rate) were 0.422 μg/cm 2 (7.84 %) at the Mississippi site and 1.001 μg/cm 2 (18.23 %) at the Texas site. Following the second application, the highest average dicrotophos DFR value occurred immediately after application and dropped to below the LOQ by 7 days after application at t he Mississippi site and by 14 days after application at the Texas site. The highest average DFR values (and percent of application rate) following application 2 were 0.180 μg/cm 2 (3.22 %) at the Mississippi site and 0.343 μg/cm 2 (6.13 %) at the Texas site. 14 days is the minimal retreatment

interval. HED determined that the Texas site data is more appropriate for use in human health risk assessment, as precipitation concerns make the Mississippi data significantly less reliable. Typically the DFR after mul tiple applications would be used for the regression analysis, however, residue data after the first application at the Texas site was used in this assessment as it provided higher dislodgeable residues values and is thus more conservative. See the summary of

this data in the table below.

Table 7 . Summary of Dicrotophos DFR Residues and Versar Regression Analysis

Results for Cotton Leaves Treated with Dicrotophos

Statistic Texas

- 1 st application

Application Rate (lb ai/A) Target Application Rate = 0. 50 lb ai/A 0.49 (first application) 0.50 (second application) Measured Average Day 0 Residue (μg/cm 2 ) 1.001 (first application) 0.343 (second application) Predicted Day 0 Residue (μg/cm 2 ) 0.936

Slope

- 0.402

Half

- life (days) 1.7

R 2 0.923
Registrant’s predicted half

- life (days) 2.33 Registrant’s R 2 0.971

Occupational Post

- application Non

- Cancer Dermal Exposure and Risk Estimate EquationsPage 25 of 32

Average Daily Dose (ADD): Potential daily exposures for occupational post

- application workers were calculated using the following formulas:

Daily Exposure (mg ai /day) = TC (cm 2 /hr) * CF1 * DFR t (μg/cm 2 ) * ET (hrs /day) * 1E

- 3 mg/μg

w here: Daily Exposure = Amount (mg ai/day) that is available for dermal absorption,

TC = Transfer coefficient (cm 2 /hr)

, DFR t = Dislodgeable Foliar Residue on day “t” ( μg/cm 2 ) , and

ET = Exposure Time (hours /day)

.

The daily doses were calculated using the following formula:

Avera ge Daily Dose (mg ai/kg/day) = [Daily Exposure (mg ai/day) * Absorption (%)] Body Weight (kg)

w here: Average Daily Dose = Absorbed dose received from exposure to a pesticide in a given scenario (mg pesticide active ingredient/kg body weight/day), Daily Exposure = Amount (mg ai/day) that is available for dermal absorption, Absorption Factor = A measure of the amount of chemical that crosses a biological boundary such as

the skin (%) , and Body Weight = Body weight determined to re present the population of interest in a risk

assessment (kg)

.

Margin of Exposure: Non

- cancer risk estimates for each application handler scenario are calculated using a Margin of Exposure (MOE), which is a ratio of the toxicological endpoint to

the daily dose of concern. The daily dermal dose received by occupational post

- application

workers w as compared to the appropriate POD ( i.e. BMDL ) to assess the risk to occupational

post

- application workers

. All MOE values were calculated using the following formula:

MOE = POD ( BMDL in mg/kg/day)

ADD (mg/kg/day)

w here:

MOE = Margin of Exposure: value used by HED to represent risk or risk estimates (unitless),

PO D = Point of Departure, and

ADD = Average Daily Dose (mg/kg/day) : the absorbed dose received from exposure to a pesticide in a given scenario

.

Occupational Post

- application Non

- Cancer Dermal Risk Estimates

Table 6

. 2 .2.2: Summary of Occupational/Commercial Post

- application Risk Estimates for Dicrotophos

. Crop/Site Activities DFR/TTR 1 DAT MOE 2

Steady State

Cotton Hand Weeding 0.928 0 1,400

0.0832 6 16,000

Scouting 0.928 0 470

0.0832 6 5,200

1. DFR = from chemical

- specific study data (MRID 44731001)Page 26 of 32

2. MOE = POD ( mg /kg/day) / Daily Dermal Dose. Daily Dermal Dose = [ DF R /TTR (μg/cm 2 ) x TC x 0.001 mg/μg x 8 hrs/day ]  BW (kg)

Although dicrotophos can be applied to cotton after bloom, exposure to dicrotophos residues during harvesting or post

- harvest activities is expected to be negligible as residues ar e expected

to be minimal after the label

- required 30

- day pre

- harvest interval and considering that dicrotophos dissipated with a half

- life of approximately 2 days from the terrestrial field studies (D276599). The assessment of pre

- harvest activities at 0 days after treatment is expected to cover any harvest

- related exposure to dicrotophos, which would not occur until 30

- days after application; all assessed post

- application exposure activities are not of concern on the day of

treatment.

Restricted Entry In terval

The REI specified on the label of 6 days is based on the acute toxicity of dicrotophos and the mitigations specified in the dicrotophos RED. Dicrotophos is classified as Toxicity Category II

via the dermal route and for eye irritation and Toxicity Category IV for skin irritation potential.

It is a strong skin sensitizer. Single day and steady

- state post

- application risk estimates were not a concern on day 0 (12 hours following application) for all post

- application activities. Under 40 CFR 156.208 (c) (2), if the product contains only one active ingredient and it is in toxicity category I I , the restricted entry interval shall be 24 hours. If the active ingredient is an organophosphorus ester that inhibits cholinesterase and that may b e applied outdoors in an area where the average rainfall is less than 25 inches per year, the restricted interval should be listed

as 72 hours. Thus, the REI on the labels meets the minimum requirements

.Page 27 of 32

Appendix A. Summary of Occupational and Re sidential Non

- cancer Algorithms

Spray Drift Non

- cancer Post

- application Algorithms

Modification To SOP Method To Account For Spray Drift and Residential Post

- Applicatio n Hand to Mouth Algorithms

The modification to SOP 3.2.2 that has been made to account for spray drift only alters Equation 3.4 from the SOPs. The modified equation is presented below and it should be used to evaluate potential risks from spray drift. This equation is the same except that an additional term has been included (DF or Drift Fraction) which provides an adjustment for the amount of drift that moves into and deposits in a non

- target area such as a lawn. This equation applies to situations where

TTR data are not available.

TTR = AR * DF * F * (1

- D) t * CF2 * CF3

where:

TTR = turf transferable residue (μg/cm 2 )

DF = drift fraction of spray drift that deposits on lawns ( unitless )

AR = application rate (lbs ai/ft 2 or lb ai/acre)

F = fraction of ai as transferable residue following application (unitless)

D = fraction of residue that dissipates daily (unitless)

t = post

- application day on for exposure is being assessed (Day 0 in this SOP)

CF2 = weight unit conversion factor (4.54 x 10 8 μg/lb)

CF3 = area unit conversion factor (1.08 x 10

- 3 ft 2 / cm 2 or 2.47 x 10

- 8 acre/cm 2 )

If chemical specific TTR data are available, the residue on Day 0 is used after it is adjusted based on the ratio of the applicable application rate for risk assessment (i.e., based on the crop of concern) and the application rate for the TTR study follo wed by an additional adjustment for the

drift fraction factor like illustrated above.

Post

- application Dermal Exposure Algorithm

– Physical Activities on Turf Exposure resulting from contacting previously treated turf while performing physical activities is calculated as shown below. Residential post

- application exposure assessment must include calculation of exposure on the day of application. Therefore, though an assessment can present exposures for any day “t” following the application, it must includ e “day 0” exposure.

E = TTRt * CF1 * TC * ET

where:

E = exposure (mg/day); TTRt = turf transferable residue on day t (μg/cm 2 ); CF1 = weight unit conversion factor (0.001 mg/μg); TC = transfer coefficient (cm 2 /hr); andPage 28 of 32

ET = exposure time (hr/day).

Dermal absorbed doses are calculated as:

where:

D = dose (mg/kg

- day);

E = exposure (mg/day);

AF = absorption factor (dermal); and

BW = body weight (kg).

Table A

- 1 : Turf (Physical Activities)

-- Inputs for Residential Post

- appli cation Dermal Exposure

Algorithm Notation Exposure Factor (units) Point Estimate(s)

AR Application rate (mass active ingredient per unit area) 0.5

F Fraction of AR as TTR

following application (if

chemical

- specific data is unavailable) L/WP/WDG 0.01

Granules 0.002

F D Daily residue dissipation

(if chemical

- specific data is unavailable) (fraction) L/WP/WDG 0.1

Granules 0.1

TC Transfer

Coefficient (cm 2 /hr) L/WP/WDG Adults 180,000
Children 1 < 2 years old 49,000

Granules Adults 200,000

Children 1 < 2 years old 54,000

ET Exposure Time

(hours per day) Adults 1.5 Children 1 < 2 years old 1.5

BW Body Weight (kg) Adults 80

Children 1 < 2 years old 11 L/WP/WDG = Liquids/Wettable Powders/Water

- dispersible Granules

Post

- application Hand

- to

- Mouth Exposure Algorithm

– Physical Activities on Turf Exposure from hand

- to

- mouth activity is calculated as follows (based on the algorithm utilized in

the SHEDS

- Multimedia model ):

E = [HR * ( F

M * SA H ) * (ET * N_Replen) * (1

- (1

- SE ) (Freq_HtM/N

- Replen) )]

where:

E = exposure (mg/day); HR = hand residue loading (mg/cm 2 ); FM = fraction hand surface area mouthed / event (fraction/event); SAH = typical surface area of one hand (cm 2 );Page 29 of 32

ET = exposure time (hr/day); N_Replen = number of repl enishment intervals per hour (intervals/hour); SE = saliva extraction factor (i.e., mouthing removal efficiency); and Freq_HtM = number of hand

- to

- mouth contacts events per hour (events/hour).

and

where:

HR = hand residue loading (mg/cm 2 );

Fai hands = fraction ai on hands compared to total surface residue from dermal transfer coefficient study (unitless); DE = dermal exposure (mg); and

SA H = typical surface area of one hand (cm 2 ).

Dose, normalized to body weight, is calculated as:

where:

D = dose (mg/kg

- day);

E = exposure (mg/day); and

BW = body weight (kg).

Table A

- 2 : Turf (Physical Activities)

– Inputs for Residential Post

- application Hand

- to

- Mouth Exposure Algorithm

Notation Exposure Factor (units) Point Estimate(s)

Fai hands Fraction of ai on hands

from dermal transfer coefficient study (unitless) Liquid formulations 0.06

Granular formulations 0.027

DE Dermal exposure (mg) Calculated

SA H Typical surface area of one hand (cm 2 ), children 1 < 2 years old 150

AR Application rate

(mass active ingredient per unit area) 0.5

HR Residue available on the hands (mg/cm 2 ) Calculated via (DE * Fai hands )/SA H

F M Fraction hand surface area mouthed (fraction/event) 0.127

N_Replen Replenishment intervals per hour 4Page 30 of 32

Table A

- 2 : Turf (Physical Activities)

– Inputs for Residential Post

- application Hand

- to

- Mouth Exposure Algorithm

Notation Exposure Factor (units) Point Estimate(s)

(intervals/hr)

ET Exposure time (hrs/day) 1.5

SE Saliva extraction factor (unitless) 0.48

Freq_HtM Hand

- to

- mouth events per hour (events/hr) 13.9

BW Body Weight

(kg) Children 1 < 2 years

old 11

Occupational Non

- cancer Handler Algorithms

Potential daily exposures for occupational handlers are calculated using the following formulas:

E=UE * AR * A * 0.001 mg/ug

where:

E = e xposure (mg ai/day),

UE = u nit e xposure (μ g ai/ lb ai),

AR = m aximum application rate according to label (lb ai A or lb ai/gal ), and

A = a rea treated or amount handled (e.g., A/day, gal/day)

.

The daily doses are calculated using the following formula:

ADD= E * AF

BW

where:

ADD = average daily dose a bsorbed in a given scenario (mg ai/ kg / day),

E = e xposure (mg ai/day),

AF = absorption fa ctor (dermal and/or inhalation), and

BW = body weight (kg)

.

Margin of Exposure: Non

- cancer risk estimates for each application handler scenario are

calculated usin g a Margin of Exposure (MOE), which is a ratio of the toxicological endpoint to the daily dose of concern. The daily dermal and inhalation dose received by occupational

handlers a re compared to the appropriate POD ( i.e.

, NOAEL) to assess the risk to occup ational handlers for each exposure route. All MOE values a re calculated using the following formula:Page 31 of 32 MOE= POD

ADD

where:

MOE = m argin of e xposure: value used by HED to represent risk estimates (unitless),

POD = p oint of d eparture (mg/kg/day)

, and

ADD = average daily dose absorbed in a given scenario (mg ai/kg/day)

.

Occupational Non

- cancer Post

- application Algorithms

Potential daily exposures for occupational post

- application workers are calculated using the following formulas:

DFR t =AR * F* (1

- D) t * ( 4 .54E8 ug

lb ) * ( 2.47E

- 8 A

cm 2 )

where:

DFR t = dislodgeable foliage residue on day "t" (μg/cm 2 ),

AR = a pplication r ate (lb ai/acre),

F = fraction of ai retained on foliage or 25% (unitless),

D = fraction of residue that dissipates daily or 10% (unitless), and

t = number of days after application day (days)

.

E=TC * DFR t * ET * 0.001 mg

ug

where:

E = e xposure (mg ai/day),

TC = t ransfer coefficient (cm 2 /hr),

DFR t = d islodgeable f oliar r esidue on day “t” (μg/cm 2 ), and

ET = e xposure t ime (hours/day).

The daily doses are calculated using the following formula:

ADD= E * AF

BW

where:

ADD = average daily dose absorbed in a given scenario (mg ai/kg/day),

E = e xposure (mg ai/day),Page 32 of 32

AF = absorption fa ctor (dermal and/or inhalation), and

BW = body weight (kg).

Margin of Exposure: Non

- cancer risk estimates for each scenario are calculated using a Margin of Exposure (MOE), which is a ratio of the toxicological endpoint to the daily dose of concern. The daily dermal dose received by occupational post

- application workers is compared to the appropriate POD ( i.e.

, NOAEL) to assess the risk to occupational post

- application workers

. All

MOE values a re calculated using the following formula:

MOE= POD

ADD

where:

MOE = margin of exposure: value used by HED to represent risk estimates (unitless),

POD = point of departure (mg/kg/day), and

ADD = average daily dose absorbed in a given scenario (mg ai/kg/day).