UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460

Date : September 15

, 2015 OFFICE OF C HEMICAL SAFETY

A ND POLLUTION PREVENTI O N

Subject: Tcrb ufo s. Occupational and Resid ential Exposure Assess m ent for the Reg i stra tion Review Risk Assessment. 0420977

P C Code: I 0500 I

Deci s ion No.: 472941

Pelilion No. : NA

Ri s k Assess m e n t Type: Occupational/Residential Exposure Asse ss ment

TXR No.: NA

M RIO No.: 44 79330 I

, 4418040I,4430130 I

From: Mathew Lloyd

, CJH 

# 11.i, -;fl{J

Ri sk Assessment Branch V il

H ea l th Effects Division (7509P) DP Barcodc: 0420977 Registratio n No.: 548 1-54 5, 548 1-

562

R eg ulat ory Action: Reg Review

Case No.: NA

CAS No.: 13071-79-9

40 CF R: 180 .352

T h ro u g h :

# ~ .... :PJ JI:

A l exa ndra LaMay

, Biologi s 

### ! i

### ~;r-rr Mic h ae l S. Metzger, Chief /. 

## L

Ri s k Assessment Branch 

### V I · H ea lth Effects Divis i on (7509 P )

Intr o duction and 

### /vi /**_//~** Nancy Keller

, Chem ist

### ~**~** S halu Shelat

, Indu s trial Hy g i e nist
Expos ure Science Adv i so r y Committee (ExpoSAC) I H ED

The Pesticide Reevaluation Division (PRO) requested th at the H ea lth Effec ts Divi s ion (HEO)

conduct an exposure a nd ri sk assess m ent for the currently reg i stered uses of t erbufos as part of

the r eg i stra tion review proce ss. Terbufos i s registered for use on corn
, sorghum

, and s ugar beets.

There are currentl y no r egiste r ed non-occupational ( r esiden tial use s) fo r terbufo s

. It is HED policy to use the best available data to as sess exposure. Severa l so urc es of generic data were

u sed in this assessment as s urro ga te data in the absence of chemica l -specific data

, in clud in g [Pe s ticide Handl e r s Exposure Database V ers ion 1

. 1 (PHED I

. I) ; and o th er chemica l- and

sce nario-specific exposure monitoring s tudi es (M RID 44 79330 I

, 44180401

, 4430130 l )]. Some

of th ese data arc proprietar y, a nd s ubje ct t o the data protection provi s ions of the Federa l

In sec ti cide, Fungicide, and Roclenticidc Ac t ( FIFRA ).

Note: This mem o r a ndum wa s reviewed by the Exposure Science Advisory Committee
( Exp oSAC) o n (07 / 24 / 14].

Page I of29Page 2 of 29 Table of Contents

1.0 Executive Summary

................................ ................................ ................................ ............. 3

2.0 Risk Assessment Conclusions and Recommendations

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

2.1 Summary of Risk Estimates

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

2.2 Label Recommendations from Occupational Assessment

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

2.3 Label Recommendations from Residential Assessment

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

2.4 Data Deficiencies and Requirements

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

3.0 Hazard Characterization

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

4. 0 Use Profile

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

5.0 Residential Exposure and Risk Estimates

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

5.1 Residential Risk Estimates for Use in Aggregate Assessment

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

5.2 Spray Drift

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

5.3 Resident ial Bystander Post

- Application Inhalation Exposure

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

6.0 Occupational Exposure and Risk Estimates

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

6.1 Occupational Handler Exposure/Risk Estimates

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

6.2 Occupational Post

- application Exposure/Risk Estimates

................................ .............. 21

6.2.1 Occupational Post

- application Inhalation Exposure/Risk Estimates

...................... 21

6.2.2 Occupational Post

- ap plication Dermal Exposure/Risk Estimates

.......................... 21 Appendix A. Summary of Occupational Non

- cancer Algorithms

................................ ............... 23 Study Summaries Used in the Occupational Handler Assessment

................................ ............... 2 6Page 3 of 29

1.0 Executive Summary

This document presents an occupational and residential exposure and risk assessment for the currently registered uses of terbufos for use in the preliminary risk assessment for registration

review

. Terbufos is a Restricted Use pesticide (RUP) registered for use on corn, sorghum, and sugar beets.

Use Profile:

T he only two terbufos end

- use formulation s currently registered are (1) a granular formulation available with 15% ai [clay

- based formulation] and (2) a 20% ai formulation [polymer

- based designed as a low dust alternative ] 1

. All the available products are classified as Restricted Use

, indicating that they may be purchased and used only by certified applicators or persons under direct supervision of a certified applicator

. As a n RUP

, the terbufos product labels contain substantial protective measures to prevent worker exposure

. Engineering controls are required to be used in conjunction with additional personal protective equipment (chemical

- resistant gloves

and a chemical

- resistant apron ).

The currently registered application rates for the agricultural uses range from 1.3 lbs ai/A to 2.6 lbs ai/A; all for ground applications conducted using closed syst ems. T he pre

- harvest interval s (PHI) depend on the crop s
, and range from 60 days to 1 50 days.

This assessment addresses occupational worker exposure and risk associated with the end

- use products for terbufos when used as directed. There is a potential for occupational exposure associated with handler activities (i.e., loading and apply ing)

. There are no registered residential

uses associated with terbufos at this time

.

Exposure Duration: For the organophosphate pesticides (O P s) , the match between the toxicological endpoint selection and the exposure duration is different than HED’s approach for conventional chemicals. The endpoint selection for OP s involves a “single day” and “steady state” approach

based on an individual chemi cal’s cholinesterase inhibition. The steady state approach is appropriate for terbufos given the toxicological and exposure profile. The “steady state” endpoint selection for terbufos overlaps with HED’s traditional short

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

- term exposures). C hronic exposure is not expected for the registered uses

, and a cancer assessment was not needed

.

Hazard Profile : Terbufos is a member of the organophosphate ( OP ) class of pesticides. Like other OPs, the initiating event in the adverse outcome pathway (AOP), also often called the mode of action (MOA), for terbufos 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

1 Past risk assessment documentation refers to the 20% ai formulation as “20CR”, although the current 20% ai formulation is referred to by its currently registered name “20G”.Page 4 of 29

nervous system . For terbufos

, AChE inhibition is the most sensitive endpoint in the toxicology database in multiple species, durations, lifestages, and routes

.

A steady state dermal point of departure ( P O D ) was selected to assess the 15G terbufos

formulation from a 28

- day dermal toxi city study in rats based on red blood cell ( RBC )

cholinesterase ( ChE ) inhibition (BMDL 10 = 1.04 mg/kg/day; BMD 10 = 1.19 mg/kg/day). No

dermal POD was selected for the 20 CR formulation as no cholinesterase inhibition was observed

in a 28

- day formulation specific study. A steady state inhalation POD was selected to address

both formulations from an oral developmental neurotoxicity study (based on RBC and brain ChE

inhibition (BMDL 10 = 0. 01 m g/kg /day; BMD 10 = 0. 02 m g/ kg /day). A total uncertainty factor of

100 0 X is appropriate for the dermal route of exposure [ 10X for interspecies extrapolation, 10X for intraspecies variation] and a total uncertainty factor of 3 000 X is appropriate for the inhalation route of exposure [10X for interspecies extrapolation, 10X for intraspecies variation, 3 0X for database uncertainty factor

. Terbufos is classified as " not likely to be carcinogenic to humans ”

.

Residential Exposure/Risk: There are no currently registered non

- occupational (residential) uses for terbufos

. However, that does not preclude non

- occupational exposure to terbufos.

Spray Drift : Terbufos end use products are formulated as two granular formulation s (15 and 20% ai end use products ) that are soil incorporated; therefore, a spray drift assessment has not been conducted.

Occupational Handler Exposure:

HED relie s on surrogate data as well as chemical

- specific data for the 15% and 20% active ingredient granular formul ation s , referred to in this document as “ 15G /20G ”

. Default assumptions established by the HED Science Advisory Council for Exposure (ExpoSAC) were used for parameters such as body weight and amount handled

. A n aggregate risk index ( ARI ) approach is used as a risk metric for the 15G /20G formulation since the toxicological effects for

the inhalation and dermal exposure routes were similar , but the LOC’s are different (dermal =

100 0 ; inhalation = 3 000).

Based on the use of engineering controls as defined o n the 15G /20G product label s
, HED used surrogate unit exposure (PHED) data, and available chemical

- and scenario

- specific exposure data to assess occupational handler risk for the dermal and inhalation routes of exposure

. With one exception, risk estimates are of concern (i.e. ARIs<1) for all loader/applicator scenarios regardless of the unit exposure data used to complete the handler assessment. The exception is one loader scenario using the Smartbox data set at the minimum labeled application rate (1.3 lb s ai/A) where the ARI >1.

The 20% polymer

- based active ingredient granular formulation is referenced in this document as

“20 CR .” For the 20 CR product, HED only quantitatively assessed the inhalation route of exposure because cholinesterase inhibition was not observed in a formulation specific dermal study . In addition, the chemical

- specific data do not represent the currently labeled application

methods for the 20 CR formulation, therefore, the data were not quantitatively applied to the

handler assessmen t for 20 CR

. The level of concern (LOC) for the inhalation risk estimate is aPage 5 of 29

margin of exposure (MOE) of 3000

. For the PHED

- based assessment, loader and applicator

inhalation MOEs represent risk estimates of concern ranging from 2 1 to 80 and 7.9 to 3 0

, respectively

. Additional q ualitative consideration of available exposure data indicates risk

estimates are of concern for loaders using the 20 CR formulation

.

Occupational Post

- application Exposure: A quantitative post

- application assessment has not been conducted for terbufos because of the way that terbufos is applied (i.e., granul e s that are soil incorporated), the timing of the application in the growing season , the frequency of application, and the lack of known activities

that would occur in the tre ated areas that might contribute to exposure. Based on the Agency's current practices, a quantitative occupational post

- application inhalation exposure assessment was not performed for terbufos 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

assessment for terbufos

.

The acute toxicity data for terbufos show that this chemical is extremely acutely toxic. Terbufos is classified as Toxicity Category I via the dermal route and wasn’t classified for acute eye

irritation because it caused 100% death in the test animals in 24 hours. However, there is negligible dermal exposure for terb ufos because of the application pattern (soil incorporated granul e s with limited potential for worker soil contact). T he reentry interval ( REI ) on the currently registered labels ( 48

- 72 hours 2 ) is adequately protective of worker exposure

.

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 ) ; other registr ant

- submitted exposure monitoring studies ( MRID 447933

- 01 ) , 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 i ncluded 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 3

.

2 Depending on geographical meteorological conditions

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

- exposure

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

- app

- exposure

- data.htmlPage 6 of 29

2.0 Risk Assessment Conclusions and Recommendations

2.1 Summary of Risk Estimates

The occupational handler assessment assumes engineering controls for loaders and closed cabs for applicators; the assessment identifie s a number of exposure scenario with risk estimates of concern, including all the crop/application rate combinations for loaders with the 15G /20G product s and 20 CR product , regardless of the handler data used for the assessment

.

For the 15G /20G product s , the loader risk estimates are of concern with the calculated ARIs

below 1 using both surrogate 4 , as well as chemical

- and scenario

- specif ic data

. Applicator risk

estimates are of concern when chemical

- specific unit exposure data are considered (ARIs >1)

, with one exception

– the 1.3 lbs ai/A rate for sweet corn

. For the 20 CR product, risk estimates

have been calculated for the inhalation r oute only based on toxi c o lo gical considerations; risk

estimates for loader s and applicators are of concern with MOE’s generally below 80 and 3 0

, respectively (LOC = 1000)

. Additional q ualitative consideration of available exposure data

indicates risk estimates are of concern for loaders using the 20 CR formulation.

A spray drift assessment was not completed for the currently registered uses of terbufos ; Terbufos end use products are fo rmulated as a granular and soil incorporated; therefore, a quantitative spray drift assessment was not conducted.

2.2 Label Recommendations from Occupational Assessment

HED has identified occupational risk concerns and defers to the Pesticide Reevalua tion Division regarding how these concerns may be addressed.

In addition, HED recommends revisiting the mandated label personal protective equipment (PPE) for use during closed cab applications. Current labels appear to mandate PPE for applicators even w ith closed cab applications, including: chemical

- resistant gloves, and apron.

2.3 Label Recommendations from Residential Assessment

There are no currently registered non

- occupational (residential) uses of terbufos

.

2.4 Data Deficiencies and Requirements

In the case of terbufos, there are no currently labeled uses that would result in foliar residue; therefore, no dislodgeable foliar residue ( DFR ) or transferable turf residue ( TTR ) data are required at this time. In the case that the registered use patt ern changes, HED will reevaluate the need for a DFR or TTR study, depending on the proposed label change.

4 PHED and AHETFPage 7 of 29

3 .0 Hazard Characterization

Acute Toxicity

The acute toxicity data for terbufos show that the chemical has a high acute toxicity category for

acute oral

, acute dermal, and acute inhalation toxicity (Category I). The data show acute eye and

acute skin irritation was classified as Toxicity Category I because it caused death in 100% of the

test animals with in 24 hours. The skin sensitization stud y was waived for terbufos because of the acute lethality.

Table A.2.1 Acute Toxicity Profile

- Te rbufos

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

870.1100 Acute oral [rat] 00112227 LD 50 = 4.5/6.3mg/kg

(signs of ChEI) I

870.1100 Acute oral [mouse] 00037467 LD 50 = 5.0 mg/kg I

870.1100 Acute oral [rat] 00037471 LD 50 = 1.3 mg/kg I

870.1100 Acute oral [rat] 00029863 LD 50 = 1.5 mg/kg (salivation, diuresis, diarrhea, disoriented locomotion, chromadocryorrhea, piloerection, body tremors) I

870.1100 Acute oral [rat] 00035121 LD 50 = 1.74/1.57 mg/kg (respiratory depression, piloerection,, clonic convulsions, expphthalmus, ptosis, lacramation, hemorrhaging, decreased motor activity) I

870.1100 Acute oral [rat] 44021601 LD 50 = 1.4/3.2 (F/M)

(tremors, salivation, exophthalmos, decreased activity) I

870.1200 Acute dermal [rabbit] 00144806 LD 50 = 0.81/0.93mg/kg I

870.1200 Acute dermal [rat] 44021603 LD 50 = 123/71 mg/kg

15G formulation A I

870.1200 Acute dermal [rat] 47512802 LD 50 = 71/32 mg/kg

20CR formulation B I

870.1300 Acute inhalation [ rat ] 41538101 LC 50 = 0. 006 mg/L ♂

LC 50 = 0.0012 mg/L (salivation, tremors, chromodacryorrhea, labored breathing, poor condition) IPage 8 of 29

Table A.2.1 Acute Toxicity Profile

- Te rbufos

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

870.2400 Acute eye irritation [rabbit] 00044957 100% deaths in 24 hrs

(dose 0.1 mg) I

870.2500 Acute dermal irritation

[rabbit] 00037467 100% deaths in 24 hrs

(dose 0.5 mL) I

870.2600 Skin sensitization

- Requirement waived due to lethality N/A

A Salivation, chromodacryorrhea, decreased activity, tremors, diuresis, anorexia, l acrimation, prostration

B T remors, decreased activity, ataxia, diuresis, salivation, exophthalmos, dyspnea, dehydration

, exophthalmos.

Toxicological PODs Used for Risk Asse ssment

The database of toxicology studies for terbufos is complete and includes developmental studies in rat and rabbit, a reproductive toxicity study, a range

- finding developmental neurotoxicity study ( DNT ) (CCA gestational component) and a definitive DNT, and a comparative cholinesterase ( ChE ) study with two components (acute, repeated). Terbufos is an OP with a

neurotoxic adverse outcome pathway (AOP) ; neurotoxicity is the most sensitive effect in all species, routes, and lifestages and is being use d in deriving POD s. Also, OPs exhibit a phenomenon known as steady state acetylcholinesterase ( 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 duration

. For the purposes of the occupational risk assessment, only the steady

- state duration is relevant to the exposure scenarios.

A steady state inhalation POD w as selected from the oral range

- finding and definitive DNT

stud ies (MRID 46214301, 46240802 ) in gestation day 20 dams and PND 21 male and female rat

pups based on RBC and/or brain ChE inhibition (BMDL 10 = 0. 01 mg /kg /day; BMD 10 = 0. 02

m g/ kg /day). For steady state inhalation exposures, a total uncertainty factor of 3 000X was applied [ 10X for interspecies extrapolation, 10X for intraspecies variation and a 3 0X for database uncertainty around the uncertainty regarding the potential neurodevelopmental effects of the OPs and because there is an inhalation study requirement for terbufos 5

.

For terbufos, there are formulation

- specific dermal toxicity studies available. For the 15G formulation, a steady state dermal POD was selected from a 28

- day dermal toxicity study (MRID

445 205 01) in rats based on RBC ChE inhibition (BMDL 10 = 1

. 04 mg/kg/day; BMD 10 = 1

. 19 mg/kg/day) in the male rat. A total uncertainty factor of 100 0 X is appropriate for dermal exposures [10X for i nterspecies extrapolation, 10X for intraspecies variation , and 10X for uncertainty regarding potential neurodevelopmental effects from OPs ]. For the 20G formulation,

cholinesterase inhibition was not observed in the route

- specific 28

- day dermal toxicity study.

In accordance with the Agency's Draft Cancer Risk Assessment Guidelines (July 2, 1999),

terbufos is classified as " not likely to be carcinogenic to humans ”.

5 P er HED’s HASPOC review: HASPOC TXR No. 0056967Page 9 of 29

A summary of the toxicological doses and endpoints for use in th e 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 Terbufos

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

E ffects

Dermal Steady State (21 days and longer) [15G] BMDL 10 = 1.04 mg/kg/day

UF A = 10x

UF H = 10x

UF DB = 10x 28

- day dermal toxicity study (MRID 44520501 ) in

rats

BMD 10 = 1.19 mg/kg/day for inhibition of RBC

cholinesterase in male rats.

Inhalation Steady State (21 days and longer) [both formulations] BMDL 10 = 0.01 mg/kg/day

UF A = 10x

UF H = 10x

UF DB = 30x DNT/RF DNT studies (MRID 46214301; 46240802)

BMD 10 = 0.02 mg/kg/day for inhibition of RBC and/or brain in GD 20 dams, PND 21 males, and

females.
Cancer (oral, dermal, inhalation) Classification: Not likely to be carcinogenic to humans

Point of Departure ( POD ) = A data point or an estimated point that is derived from observed dose

- response data and used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. BMDL10 = benchmark dose where there is 10% inhibition. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = potential variation in sensitivity among members of the human population (intraspecies). UF L = use of a LOAEL to extr apolate a NOAEL. UF S = use of a short

- term study for long

- term risk assessment. FQPA SF = FQPA Safety Factor. MOE = margin of exposure. LOC = level of concern. N/A = not applicable.

Absorption

Since the steady

- state dermal POD is based on route

- specific toxicity studies, an absorption

factors is not necessary to estimate exposure. Since inhalation absorption data are not available, toxicity by the inhalation route is considered to be equivalent to the estimated toxicity by the oral route of exposure.

Body Weight 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 w eight of 69 kg was used. While the endpoint of concern, RBC 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

effe cts.

4 .0 Use Profile

Terbufos is a broad spectrum insecticide and is currently registered as a granular formulation that

is only applied via soil incorporat ion . It is classified as Restricted Use and may be purchased and used only by certified applicators or persons under their direct supervision. As a n RUP , the

terbufos product labels contain substantial protective measures to prevent worker exposure; (Section 6.0 provide more information on personal protective equipment).Page 10 of 29

Terbufos is an RU P intended for broad spectrum application to corn, sorghum, and sugar beet fields via ground

- based application equipment. Terbufos loaders must use closed system engineering controls, and wear l ong

- sleeved shirt and long pants , chemical

- resistant gloves, a nd

a chemical

- resistant apron. Applicators for terbufos applications must use enclosed cabs and equivalent handler PPE 6

. The available product labels indicate that the product can be used once per growing season (early season) , depending on the pest to be treated. The intended pests for the maximum application rates are generally either nematodes or rootworms.

Both the 15G and the 20G product labels require soil incorporation ; Table 3.1 (below) provides additional information on a per crop basis

. There is an SLN label associated with the 15G product that has an application rate 2X higher than the Section 3 terbufos labels.

Table 3.1. Summary of Directions for Use of Terbufos

.
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) Use Directions and

Limitations

Co rn

Field corn/pop/sweet

corn At

plant/postemerg

ent incorporated;

soil incorporated 5481

-

545/547/562 1.3 1/year 1.3

Banded or in

- furrow applications; Do not harvest sweet corn w/in 60 days of application

Field corn/pop/sweet

corn At

- plant; soil incorporated SLN920001

– North

Carolina 2.6 1/year 2.6

Sorghum

Sorghum

At

- plant; soil incorporated 5481

-

545/547/562 1.7 1/year 1.7 Banded or knifed

- in applications; Do not harvest grain sorghum fodder w/in 100 days of application
Sugar Beets

Sugar Beets

At

- plant; soil incorporated 5481

-

545/547/562 1.96 1/year 1.96 Banded or in

- furrow applications; Do not harvest sugar beets or feed tops to

livestock w/in 150 days of application; Soil incorporate

– no deeper

than 2 inches

6 Applicators are required to use closed cabs and they “must wear the PPE required for handlers using engineering controls.” [5481

- 5454/562]Page 11 of 29

5 .0 Residential Exposure and Risk Estimates

There are currently no registered non

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

5. 1 Residential Risk Estimates for Use in Aggregate Assessment

Terbufos is a Restricted Use Pesticide (RUP) and there are no currently registered non

occupational (residential) uses of terbufos . Based on the labeled use pattern and the exposure profile of terbufos , there is no recomme nded 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. However, terbufos end use products are formulated as a granular and will not result in spray drift due to how it is applied ( at

- plant/ post

- emergent soil incorporation )

.

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 Ro denticide Act Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on March 2, 2010 ( http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html ). The agency has evaluated the SAP report and has developed a Volatilizat ion 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, route

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

terbufos

.

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 t ask. 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.

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

- HQ

- OPP

- 2014

- 0219Page 12 of 29

The occupational handler assessment for terbufos relies on both PHED

- based a s well as

chemical

- and scenario

- specific data to address loader and applicator risk estimates. Appendix B summarizes the occupational exposure and risk characterization associat ed with the two available terbufos granular formulations.

Based on the anticipated use patterns and current labeling, types of equipment

, and techniques that can potentially be used, occupational handler exposure is expected from the registered uses of t erbufos

. Given all of the information above, the scenarios that have been developed as occupational handler scenarios for terbufos to best represent the registered use pattern (i.e., corn, sorghum, sugar beets) includ e :

 loading granular formulations 8 (PHED data

– Engineering Controls);

 loading 15G /20G formulation in “Lock

- N

- Load” packaging (completed using chemical

and scenario

- specific data);

 loading 15G /20G formulation in “ Smartbox ” packaging (completed using scenario

specific data);

 applying g ranular formulations 9 using ground

- based equipment (PHED data

– Engineering Controls);

 applying 15G /20G formulation using in

- the

- row planters and closed tractor cabs (using

chemical

- and scenario

- specific data); and

 applying 15G /20G formulation using Smar tbox p lanters and closed tractor cabs (using

scenario

- specific data);

Occupational Handler Exposure Data and Assumptions

A series of assumptions and exposure factors served as the basis for completing the occupational

handler risk assessments. Each assu mption and factor is detailed below on an individual basis.

Application Rate : Exposure and risk estimates calculated use maximum application rate

information for each of the relevant crops. See Section 4 .3 for additional information.

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 Tas k 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 ha ndler exposure that are used in this assessment, known as “unit exposures”, are outlined in the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table 9 ”, which, along with additional information on HED policy on use of surrogate data, incl uding descriptions of the various sources, can be found at the Agency website 10

.

8 Relevant to both 15G/20G and 20CR formulations

9 Available: http://www.epa.gov/opp00001/science/ha ndler

- exposure

- table.pdf

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

- exposure

- data.htmlPage 13 of 29

The unit exposures associated with the chemical specific data referenced above has been used and described extensively in past HED risk assessments 11

. The available chemical

- and scenario

specific data has been reassessed and quantitatively incorporated into this assessment where possible 12

.

The available handler unit exposure data used in the terbufos assessment includes:

1. Unit exposures derived from HED surrogate unit exposure guide [PHED

- based]

2. Unit exposures derived from HED’s review of terbufos chemical specific data (15G formulation)
[MRID 447933

- 01 ]

3. Unit exposures derived from HED’s review of scenario

- specific Smartbox data (chlorethoxyfos granular) [MRIDs 441804

- 01/443013

- 01 ]

The studies are described in additional detail in Appendix B.

In the case of terbufos, the unit exposure data used from various occupational handler unit exposure sources can be summarized as follows:

Table 6.1 Occupational Handler Unit Exposure Source Summary

Source 1 Dermal Unit Exposure (ug/lb ai handled) Inhalation Unit Exposure (ug/lb ai handled)

Unit exposures derived from HED surrogate unit exposure guide [PHED

- based] Loader: 8.6
Applicator: 2 Loader: 0.083
Applicator: 0.22

Unit exposures derived from
HED’s review of terbufos chemical specific data (15G formulation) [MRID 447933

- 01 ] 2 Loader: 0.074
Applicator: 0.05 Loader: 0.0118
Applicator: 0.00146

Unit exposures derived from
HED’s review of scenario

specific Smartbox data (chlorethoxyfos granular) [MRIDs 441804

- 01/443013

- 01 ] 2 Loader: 0.2
Applicator: 0.81 Loader: 0.003
Applicator: 0.12

1

– Tables 6.1.1 and 6.1.2 provide the occupational handler risk estimates

2

– Study descriptions can be found in Appendix B.

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

 80 acres loading groundboom applications and applying via ground equipment on typical

11 Dawson, The revised Occupational and Residential Exposure aspects of the HED Chapter of the Reregistration Eligibility Decision Document (RED) for Terbufos, Case #838564, PC Code 105001, DP Barcode D258665

12 Lloyd, “ Terbufos. Chemical Specific Unit Expos ure Data Review “Occupational Exposure and Risk Assessment for Loaders and Applicators Handling Terbufos Products and Supporting Worker Exposure Studies” D 422600”Page 14 of 29

field crops (e.g.

, sweet corn )

,

 200 acres for loading groundboom applications and applying via ground equipment on high acreage crops (e.g

., field corn, sugar beets).

E xposure Duration:

HED typically classifies exposures from 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 pressu re triggering the use of the pesticide, and the cultural practices surrounding that use site. For the organophosphate pesticides, the match between the toxicological endpoint selection and the exposure duration is different than HED’s approach for convent ional chemicals. The endpoint selection for organophosphate 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 terbufos given the

toxicolo gical and exposure profile. The “steady state” endpoint selection for terbufos overlaps
HED’s traditional short

- term exposure duration endpoint selection and is considered health protective for occupational handlers that apply commercially over longer per iods 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 agribusines s and/or commercial applicators who may apply a produ ct over a period of weeks (e.g. completing multiple applications for mult iple clients within a region).

Mitigation/Personal Protective Equipment: Estimates of dermal and inhalation exposure were

calculated based on the current PPE/engineering control requirements on the terbufos product

labels . Specifically, the most recent Agency R ED required engineering controls such as closed

cabs and closed mixi ng/loading systems for occupational handlers. All current terbufos labels require this level of personal protection for occupational handlers.

Combining Exposures/Risk Estimates:

For the 15G /20G formulation , a total aggregated risk index (ARI) is used si nce the LOC values for dermal exposure (100 0 ) and inhalation exposure ( 3 000 ) are different. The target ARI is 1; therefore, ARIs of less than 1 are risk estimates of concern. The aggregate risk index (ARI) is

calculated as follows : Aggregate Risk Index (

ARI) = 1÷ [(Dermal LOC ÷ Dermal MOE) + (Inhalation LOC ÷ Inhalation MOE)]

For the 20 CR product, risk estimates are not combined for the dermal and inhalation routes of exposure. Based on the 20 CR formulation specific dermal study not identifying cholinesterase inhibition, only quantitative inhalati on risk estimates are presented, based on an inhalation LOC

of 3000

.

Summary of Occupational Handler Non

- Cancer Exposure and Risk Estimates

Occupational handler risk estimates are presented using both HED’s standard occupational exposure methodology and chemical specific handler data. As discussed above, the chemical

specific data set is quantitatively incorporated into the occupational handle r risk estimation of thePage 15 of 29

15G /20G product, but not the 20 CR product

. For the 15G product , combined (dermal + inhalation) occupational handler risk estimates are presented using the ARI approach [Table 6.1.1]. Table 6.1.2 summarizes the route

- specific inhala tion risk estimates for the 20 CR product

.

15G /20G Risk Estimate s and Characterization

Table 6.1.1. identifies risk estimates for both HED’s PHED

- based assessment and the occupational handler assessment incorporating chemical

- specific unit exposure data; both approaches are laid out using the ARI approach (combined dermal and inhalation).

PHED

- Based Assessment:

B ased on the engineering control requirement that is part of the 15G label, risk estimates are of

concern for the PHED

- based steady state assessment for both loaders and applicat ors, with ARIs less than 1 for all crop application rates and scenarios for bot h loaders and applicators. The target ARI is 1; therefore, ARIs of less than 1 are risk estimates of concern. ARI’s range from 0.0 04 to
0.0 2 for loaders and 0.0 02 to 0.0 1 for applicators.

Incorporating Chemical

- specific Data:

Additional chemical

- specific 15G /20G handler data are available for terbufos that have been incorporated into this assessment. Specifically, Table 6.1.1 identifies risk estimates for each relevant exposure scenario using the PHED and chemical specific unit exposure data.

HED believes the exposure data used in the assessment is an appropriate match for the currently registered 15G product. Participants in the study used engineering controls and PPE that is reflective of current label requirements. The chemi cal

- specific study results indicate low exposure levels as would be expected given the exposure scenarios that were monitored (i.e., lower exposure activities with high levels of personal protection). While the majority of whole

body dosimeters showed de t ectable residues of terbufos , a high percentage of the field samples

of other matrices were less than the limit of detection (LOD) or limit of quantification (LOQ). In such cases, a numerical value of one

- half of the LOD or LOQ , respectively, was u sed in the calculation of unit exposure. Residues above the LOQ were corrected for the field fortification

recovery from the level closest to the value of the detected residue. Inhalation unit exposure values were calculated assuming a ventilation rate of 16.7 L /min for loaders and 8.3 L/min for applicators. The target ARI is 1; therefore, ARIs of less than 1 are risk estimates of concern. ARI’s range from 0.0 36 to 0. 18 for loaders and 0. 27 to 1.4 for applicators. Using the chemical

specific data available, occu pational handler risk estimates are of concern (i.e., ARIs <1 ) for all

loader scenarios assessed , and all except one applicator scenario

.

Incorporating Smartbox ® Data:

Two non

- chemical specific exposure stud ies were used to assess the use of SmartBox ® technology for the mixing/loading of granular formulations terbufos ground applications, and the application by ground equipment. HED has identified the Smartbox exposure data used in the assessment to be an app ropriate match for the currently registered terbufos products (15G/20G). ARI’s range from 0.0 1 to 0. 61 for loaders and 0. 004 to 0.018 for applicators. Using the scenario

specific data available, occupational handler risk estimates are of concern (i.e., AR Is <1 ) for all

of the loader and applicator scenarios assessed.Page 16 of 29

Table 6 .1. 1. Steady

- State Occupational Exposure and Risk Estimates for Terbufos (15G /20G )

. All estimates reflect engineering controls

.

Exposure Scenario Crop or Target Data Source

for

Assessment 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 (Engineering Controls) Mitigation Level

(Engineering Controls) Dose (mg/kg/day) 4 MOE 5 Dose (mg/kg/day) 6 MOE 7 ARI 8

Loader

Loader

– ground based tractor applications Sweet corn PHED A 8.6 0.083

1.3 80 A/day 0.013 80 0.000125 80 0.02

Chem

Specific B 0.074 0.0118 0.000112 9300 0.0000178 560 0.18

Smartbox C 0.2 0.003 0.000301 3500 0.00000452 2200 0.61

Loader

– ground based tractor applications Pop corn PHED A 8.6 0.083

1.3 200 A/day 0.0325 32 0.000313 32 0.008

Chem

Specific B 0.074 0.0118 0.000278 3700 0.0000445 220 0.072

Smartbox C 0.2 0.003 0.000754 1400 0.0000113 880 0.24

Loader

– ground based tractor applications Sorghum PHED A 8.6 0.083

1.7 200 A/day 0.0423 25 0.000409 24 0.0061

Chem

Specific B 0.074 0.0118 0.000365 2800 0.0000581 170 0.056

Smartbox C 0.2 0.003 0.000986 1100 0.0000148 680 0.19

Loader

– ground based tractor applications Sugar Beets PHED A 8.6 0.083

1.97 200 A/day 0.0491 21 0.000474 21 0.0053

Chem

Specific B 0.074 0.0118 0.000423 2500 0.0000674 150 0.049

Smartbox C 0.2 0.003 0.00114 910 0.0000171 580 0.16

Loader

– ground based tractor applications Sweet corn

- SLN PHED A 8.6 0.083

2.6 80 A/day 0.0259 40 0.000251 40 0.01

Chem

Specific B 0.074 0.0118 0.000223 4700 0.0000355 280 0.092

Smartbox C 0.2 0.003 0.0259 40 0.000251 40 0.01

Loader

– ground based tractor applications Field corn

- SLN PHED A 8.6 0.083

2.6 200 A/day 0.0648 16 0.000626 16 0.004

Chem

Specific B 0.074 0.0118 0.000558 1900 0.000089 110 0.036

Smartbox C 0.2 0.003 0.00151 690 0.0000226 440 0.12Page 17 of 29

Table 6 .1. 1. Steady

- State Occupational Exposure and Risk Estimates for Terbufos (15G /20G )

. All estimates reflect engineering controls

.

Exposure Scenario Crop or Target Data Source

for

Assessment 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 (Engineering Controls) Mitigation Level

(Engineering Controls) Dose (mg/kg/day) 4 MOE 5 Dose (mg/kg/day) 6 MOE 7 ARI 8

Applicator

Ground Application Sweet corn PHED A 2.1 A 0.22 A

1.3 80 A/day 0.00301 350 0.000332 30 0.0097

Chem

Specific B 0.0 485 B 0.00 146 B 0.000073 14000 0.0000022 4500 1.4

Smartbox C 0.12 0.81 0.00122 850 0.000181 55 0.018

Ground Application Field corn PHED A 2.1 A 0.22 A

1.7 200 A/day 0.00986 110 0.00108 9.3 0.003

Chem

Specific B 0.0 485 B 0.00 146 B 0.000239 4400 0.00000719 1400 0.42

Smartbox C 0.12 0.81 0.00399 260 0.000591 17 0.0055

Ground Application Field corn PHED A 2.1 A 0.22 A

1.97 200 A/day 0.0114 91 0.00126 7.9 0.0026

Chem

Specific B 0.0 485 B 0.00 146 B 0.000277 3800 0.00000833 1200 0.36

Smartbox C 0.12 0.81 0.00462 230 0.000686 15 0.0049

Ground Application Sweet corn

- SLN PHED A 2.1 A 0.22 A

2.6 80 A/day 0.00603 170 0.000664 15 0.0049

Chem

Specific B 0.0 485 B 0.00 146 B 0.000146 7100 0.00000441 2300 0.69

Smartbox C 0.12 0.81 0.00243 430 0.000362 28 0.0091

Ground Application Field corn

- SLN PHED A 2.1 A 0.22 A

2.6 200 A/day 0.0151 69 0.00165 6.1 0.002

Chem

Specific B 0.0 485 B 0.00 146 B 0.000365 2800 0.000011 910 0.27

Smartbox C 0.12 0.81 0.0061 170 0.000904 11 0.0036

1 PHED/ (Eng. Controls [EC] unless otherwise noted ).

A Unit exposures derived from HED surrogate unit exposure guide [ PHED

- based]

B Unit exposures derived from HED’s review of terbufos chemical specific data (15G formulation) [MRID 447933

- 01 ]

C Unit exposures derived from HED’s review of scenario

- specific Smartbox data (chlorethoxyfos granular) [MRIDs 44 1804

- 01/443013

- 01 ]

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

- 545/562 ).

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 ( 69 kg).Page 18 of 29 5 Dermal MOE = Dermal POD ( 1.04 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 ( 69 kg).

7 Inhalation MOE = Inhalation BMDL10 ( 0. 01 mg/kg/day)/ Inhalation Dose (mg/kg /day).

8 ARI = Aggregate Risk Index = 1÷ [(Dermal LOC ÷ Dermal MOE) + (Inhalation LOC ÷ Inhalation MOE)].Page 19 of 29

20 CR Risk Estimate and Characterization

Table 6.1.2 identifies risk estimates for HED ’s PHED

- based inhalation exposure assessment for

the 20 CR terbufos product

.

PHED

- Based Assessment: Based on the engineering control requirement that is part of the 20 CR label, risk estimates are of

concern for the PHED

- based steady state assessment for both loaders and applicators, with risk

estim ates ranging from 2 1 to 80 for loaders and 7.9

- 3 0 for applicators, respectively. The level of concern for the inhalation exposure assessment is 3000 . A quantitative exposure assessment was not conducted for the dermal route of exposure because cholinestera se inhibition was not

observed in route

- specific toxicity studies.

The PHED

- based risk estimates presented below in Table 6.1.2 are conservative given the significantly lower exposure potential for the polymer based formulation compared to the
surrogate g ranular loading scenario available in PHED. That surrogate unit exposure value is based on a clay

- based granular product. However, the inhalation risk estimates for both loaders and applicators are significantly below the LOC of 3000 using the PHED

- based a ssessment.

Incorporating Chemical

- specific Data: As discussed above in Section 6.1, the chemical

- specific data for the 20 CR formulation of terbufos was not used quantitatively used in the occupational handler assessment. However, t he

20 CR portion of the chemical

- specific exposure study is useful for qualitatively comparing the exposure profiles of the two available terbufos formulations. A n important aspect of characterization is that the 20G formulation is based in a polymer matrix and presents significa ntly lower inhalation exposure for workers than the clay

- based 15G formulation. Using

the PHED

- based inhalation unit exposures to quantify inhalation risk is conservative in this case because the PHED granular formulations are clay

- based and “dustier” than the polymer

formulation.

R isk managers may also qualitatively consider the existing 15G data set for applicators to represent the inhalation exposure profile for applicators of the 20G formulation

, recognizing that the 20G formulation represents a lower potential inhalation exposure profile

. Route

- specific inhalation MOEs for the 15G product are available in Table 6.1.1. Inhalation MOEs for loaders range from 1 10

- 560 , depending on the exposure scenario. Route

- specific inhalation MOEs for applicators rang e from 910

- 45 00 , depending on the exposure scenario.Page 20 of 29

Table 6 .1. 2. Steady

- State Occupational Exposure and Risk Estimates for Terbufos (20 CR )

. All

estimates reflect engineering controls

. LOC= 3000

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 Inhalation

Mitigation Level
(Engineering Controls) Mitigation Level

(Engineering Controls) Dose (mg/kg/day) 4 MOE 5

Loader

Loader

– ground based tractor applications Sweet corn N/A 0.083 A 1.3 80 A/day 0.000125 80

Loader

– ground based tractor applications Field corn N/A 0.083 A 1.3 200 A/day 0.000313 32

Loader

– ground based tractor applications Sorghum N/A 0.083 A 1.7 200 A/day 0.000409 24

Loader

– ground based tractor applications Sugar Beets N/A 0.083 A 1.96 200 A/day 0.000474 21

Applicator

Ground Application Sweet corn N/A 0.22 A 1.3 80 A/day 0.000332 30

Ground Application Field corn N/A 0.22 A 1.7 200 A/day 0.00108 9.3

Ground Application Field corn N/A 0.22 A 1.96 200 A/day 0.00126 7.9

1 PHED/ (Eng. Controls [EC] unless otherwise noted).

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

- 562).

3 Exposure Science Advisory Council Policy #9.1.

4 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 ( 69 kg).

5 Inhalation MOE = Inhalation BMDL10 (0. 01 mg/kg/day)/ Inhalation Dose (mg/kg /day).

A Unit exposures derived from HED surrogate unit exposure guide [ PHED

- based]Page 21 of 29

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, 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 target that was treated, the type of pesticide application, and the chemical’s degradation prope rties. 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 Inhalation 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

pes ticides. 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 Marc h 2, 2010 ( http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html ). The agency has evaluated the SAP report and has developed a Volatilization Screening Tool and a subsequent Volatilization Screening Analysis ( http://www.regulations.gov/#!docketDetail;D=EPA

- HQ

OPP

- 2014

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

- specific inhalation toxi cological studies) or further analysis is required for terbufos.

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 Age ncy 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 pesticides outdoors is likely to result in higher exposure than post

- application exposure

.

6

. 2 .2 Occu pational Post

- application Dermal Exposure/Risk Estimates

A quantitative post

- application assessment has not been conducted for terbufos because terbufos is: 1) applied pre

- plant or pre

- emergent in the growing season, 2) soil incorporated, and 3)

because t he early

- season timing of application, the frequency of application (1X per year), create limited worker exposure to soil contact at planting.

In accordance with 40 CFR 158, dislodgeable foliar residue ( DFR ) data are required for all occupational (e.g., crop, nursery, greenhouse use sites) or residential (e.g., ornamental and vegetable gardens, pick your own farms, retail tree farms) uses that could result in post

-Page 22 of 29

application exposure to foliage. In the case of terbufos, there are no currently labeled use s that would result in foliar residue; therefore, no DFR or TTR data are required at this time. In the case that the registered use pattern changes, HED would reevaluate the need for a DFR or TTR study, depending on the proposed label change.

The REI specified on the existing labels is based on the acute toxicity of terbufos [ 48 hours and 72 hours in outdoor areas where average rainfall is less than 25 inches] . Terbufos is classified as Toxicity Category I via the dermal route and Toxicity Category I f or skin irritation potential. It was excepted from classification as a skin sensitizer because of terbufos’ acute lethality.

Because of the limited worker exposure profile (soil

- incorporation), the REI on the labels is adequate to protect for worker expo sure. Therefore, the [156 subpart K] Worker Protection Statement interim REI of 48/72 hours is adequate to protect agricultural workers from post

application exposures to terbufos.Page 23 of 29

Appendix A. Summary of Occupational Non

- cancer Algorithms

Occu pational Non

- cancer Handler Algorithms

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

w here: Average Daily Dose = Absorbed dose receiv ed 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 t hat crosses a biological boundary such as the skin and lungs (%) , and 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 dose of concern. The daily dermal and inhalation dose received by occupational

h andlers 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 following 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),

POD = 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

.Page 24 of 29

Appendix B. Occupational Handler Exposure and Risk Estimate Matrix

Table B .1: Occupational Exposure and Risk Estimate Matrix

Unit Exposure Data Type Handler Assessment Type (15G /20G ) Comments Handler Assessment Type (20 CR ) Comments

Dermal Inhalation Combined* Dermal Inhalation Combined *

Loader (PHED

based) Y Y Y

– ARI Standard handler

assessment ; surrogate UE is clay

- based matching the

terbufos

formulation N Y N Standard handler

assessment;
conservative because of clay

based surrogate

chemical UE

Loader (chemical

specific)

Y Y Y

- ARI Chemical and

exposure scenario specific unit exposure

values N Y

-

qualitative N Qualitative

consideration of chemical specific

15G data possible, although 20 CR

has a lower

exposure

p otential

Loader (scenario

specific) [ SmartBox® ] Y Y Y

- ARI Equipment

specific closed loading study

– not chemical

specific but applicable via data bridging N N N Terbufos is

available for

SmartBox® application with

the 15/20G

formulation

Applicator (PHED

based) Y Y Y

- ARI Standard handler

assessment ; surrogate UE is clay

- based matching the

terbufos

formulation N Y N Standard handler

assessment;
conservative because of clay

based surrogate

chemical UEPage 25 of 29 Table B .1: Occupational Exposure and Risk Estimate Matrix

Unit Exposure Data Type Handler Assessment Type (15G /20G ) Comments Handler Assessment Type (20 CR ) Comments

Dermal Inhalation Combined* Dermal Inhalation Combined *
Applicator (chemical

specific)

Y Y Y

- ARI Chemical and

exposure scenario specific unit exposure

values N Y

-

qualitative N Qualitative

consideration of chemical specific

15G data possible, although 20 CR

has a lower

exposure

p otential Applicator (scenario

specific) [ SmartBox® ] Y Y Y

- ARI Equipment

specific closed loading study

– not chemical

specific but applicable via data bridging N N N Terbufos is

available for

SmartBox® application with

the 15/20G

formulation

Route

- specific assessments are quantitative unless otherwise noted

 ARI = Aggregate Risk Index ApproachPage 26 of 29

Study Summaries Used in the Occupational Handler Assessment

A chemical

- specific occupational handler study using the two granular end use product formulations is available for terbufos (MRID 44793301) 13 . That data review was originally part of the terbufos RED ORE chapter (D258665) and updated to reflect current label mitigations and best data practices (D422600). For additional information on the chemical

- specific exposure studies, see the study overviews available in “ The revised Occupational and Residential Exposure aspects of the HED Chapter of the Re registration Eligibility Decision Document (RED) for Terbufos, Case #838564, PC Code 105001, DP Barcode D258665. ” Because of the label changes that have been implemented for terbufos since the 2006 RED, HED is using the

available chemical

- specific data to reflect the current occupational handler exposure scenarios. Specifically, HED uses chemical

- specific unit exposure data for the 15G formulation, but not the 20G formulation. Since the 2006 RED, engineering controls plus PPE are required for both the

15G a nd 20G formulations. Additionally, data are available for the Smartbox ® application system (MRIDs 44180401/44301301), a proprietary type of closed loading system for granular pesticides.

The available chemical and scenario

- specific data were used to the extent possible to characterize the occupational handler assessment for terbufos:

 15G Study (MRID 44793301)

o The exposure data detailed in this study is relevant for the current occupational handler scenarios registered for terbufos. Specifically, this exposure data details loading and application of the 15G formulation on terbufos using personal protective equip ment/engineering controls measures on par with currently registered label requirements.

The field portion of this study was conducted at 15 sites in central Nebraska during the 1998 growing season. All totaled, 30 individual farmworkers were monitored i n this study. At each site, two farmworkers (one loaded and the other completed the application) were monitored during the application, with soil incorporation, of terbufos 15G using “Lock

- N

- Load” type packaging, typical corn planters, and closed cab trac tors (open cabs were used for 2 replicates). All planters were either 6 or 8 row devices. Corn was treated at an average application rate of 1.23 lb ai/acre (the label maximum is 1.3 lb ai/acre) at planting. The total amount of active ingredient loaded in this study ranged from 66 to 96 pounds while the total amount of active ingredient applied in this study ranged from 35.8 to 81.9 pounds. The exposure time periods for loaders ranged from 0.37 to 0.78 hours while the time periods for the applicators ra nged from 3.8 to 8.7 hours. Exposure monitoring for dermal and inhalation exposure was completed using

whole

- body dosimetry, aqueous handwashes, aqueous glove washes, facial/neck wipe, inhalation monitoring in the breathing zone using personal sampling pu mps, and inhalation monitoring in the breathing zone using personal sampling pumps pulling air through a respirator cartridge attached to the sampling device. All data except for the glove washes and the respirator cartridge protected inhalation monitorin g data were used in the risk assessment. These data were not used

13 Chemical

- specific data review: Lloyd, “ Unit Exposure Calculations and Summary for “ Occupati onal Exposure and Risk Assessment for Loaders and Applicators Handling Terbufos Products and Supporting Worker Exposure Studies ” D 422600Page 27 of 29

in the assessment because the monitoring techniques are not considered to be acceptable approaches by the Agency.

The loaders in this study used the “Lock

- N

- Load” type packaging as describ ed above. Additionally, they wore normal work clothing, nitrile gloves, and a chemical

- resistant apron (i.e., treated as a double layer of protection by the Agency for the purposes of this assessment). The applicators in this study used closed cabs as de scribed above. Additionally, they wore normal work clothing, nitrile gloves, coveralls, protective eyewear, and an air purifying respirator with and organic vapor removing cartridge.

The results of this study indicate very low exposure levels as would be expected given the exposure scenarios that were monitored (i.e., lower exposure activities with high levels of personal protection). There was a high percentage of values that were less than either the limit of detection (LOD) or limit of quantificatio n (LOQ). In such cases, the values used to calculate the unit exposure values were either 1⁄2 of the LOD or LOQ as appropriate. While a majority of the

whole

- body dosimeters contained detectable residues of terbufos, hand, face and neck exposures

were gener ally below the level of quantification. The dermal unit exposure was estimated to be 0.074 and 0.05 ug/lb ai handled for loaders and applicators, respectively. Approximately half the inhalation loader samples were non

- detects. Respiratory terbufos exposur e was estimated to be 0.0118 and 0.00146 ug/lbs ai handled for loaders and applicators, respectively.

 20CR Study (MRID 44793301)

o The exposure data detailed in this study is relevant for open pour scenarios and open cab application. Current label requirem ents require “lock and load” type engineering controls and closed cab applications on the product labels. This study data is relevant for a qualitative comparison of the magnitude of exposure for occupational handlers; this comparison is useful to compare the polymer

- based 20G formulation against the higher clay

- based 15G formulation as OPP risk managers assess potential risk mitigation options for the terbufos formulations currently registered. However, the 20G portion of the chemical

- specific data is

not used quantitatively for the occupational assessment because of extensive risk mitigation measures implemented since the 1999 HED Human Health Risk

Assessment.

 Smartbox ® Handler Studies (MRIDs 44180401 / 44301301 )

In addition to th e avaialable chemical

- specific data, two non

- chemical specific exposure stud ies

were used to assess Smartbox systems, a proprietary type of closed loading system designed for granular pesticides. The exposure study was used to assess the use of SmartBox ® t echnology for the mixing/loading of granular formulations for aerial and ground applications of Chlorethoxyfos , and the application by ground equipment. Separate data evaluation recordsPage 28 of 29

(DERs) were completed for the mixing/loading [1] and applicator [2] stu dies ; only ground application values are relevant for the terbufos scenarios. A summary of the study is presented

below.

MRID 44180401

- Chlorethoxyfos Loader Exposure Study During Loading of Fortress 5G Granular Insecticide Using the SmartBox ® System D uring Planting in the Midwest : The purpose of the study was to determine the exposure to chlorethoxyfos from workers performing loading operations using Fortress 5G/SmartBox® product containers in the Midwest. The 5G product is delivered solely through closed

- handling and application SmartBox® system. Loader exposure to Fortress 5G in the SmartBox® is based on the use of a long

- sleeved shirt, long pants, shoes plus socks and chemical

- resistant gloves.

The study monitored occupational handlers prepari ng and applying Chlorethoxyfos to corn at planting in the Midwest. In the study, loaders set up one load of twelve Smartbox® systems each containing 50 pounds of formulation for a single twelve row corn planter set on 30” row spacing. The complete work cyc le for each monitoring unit included removing twelve used Smartbox® product containers from the planter, the replacement of twelve full product containers, and opening the valves to fill the Smartbox® reservoirs from the full product containers. Each loade r monitoring unit (MU) was exposed to 600 pounds of product formulation or 30 pounds of active ingredient.

During loading operations, using twelve row planters, three individual workers were monitored for dermal and respiratory exposure to chlorethoxyfos. A total of 15 MUs were obtained at 3

sites. All participants were local farmers or farm workers and were previously experienced in the ground application of pesticides.

Results indicate loader dermal exposure below the level of detection (LOD) and negligible respiratory exposure to chlorethoxyfos regardless of wind direction or work habits. The majority of dosimeter samples had no detectable residues; therefore, actual exposures may be significantly less than calculated exposures since samples belo w the level of quantitation (LOQ) were assumed to be 1⁄2 the LOQ. Respiratory chlorethoxyfos exposure was estimated to be 0.003 μg/lb ai handled, and dermal exposure was estimated to be 0.2 μg/lb ai handled.

MRID 44301301

- Chlorethoxyfos Applicator Exposure Study during Application of Fortress® 5G Granular Insecticide using the Smartbox® System during Corn Planting in the
Midwest: The purpose of this study was to monitor chlorethoxyfos exposure to applicators who were operating enclosed

- cab tractors while applying Fortress 5G/SmartBox®. The granular insecticide was applied at the maximum label rate of 3.25 lb of formulation per acre of

corn. Ind i vidual workers were monitored for dermal and inhalation exposure to chlorethoxyfos. The experiment was conducted at three sites as required by the guidelines. All sites were in Illinois; two of the three are at the same street address. The sites are reported to be

[1] L. LaSota. Evaluation of Loader Exposure Data Submitted as a Part of the Conditional Registration of Fortress 5G ( Chlorethoxyfos). EPA MRID: 44180401. 1/23/1997. D232274.

[2] J. Arthur. Review of “Chlorethoxyfos Applicator Exposure Study during Application of Fortress® 5G Granular Insecticide using the Smartbox  System during Corn Planting in the Midwest.” EPA MR ID: 443013

- 01.

7/27/1998. D238361.Page 29 of 29

typical of sites where Fortress® 5G is used. The study was conducted in the time

- frame of t he typical corn

- planting season in the midwestern corn belt (mid

- A pril through late May).

Applicators primarily remained in the enclosed cab tractors and wore appropriate personal protective clothing; long sleeve shirt, long pants, shoes and socks. In ad dition, under their work clothes, each applicator wore a long

- sleeved t

- shirt and ankle

- length underwear tights as whole

body dosimeters. Those occasions where the worker exited the enclosed cab to perform routine,

but non

- pesticide

- loading functions (eg, to perform seed corn loading) were recorded, including a description of the activity and duration.

The average corn

- planting acreage per day is reported to be 125 to 150, with a maximum of 180

acres. This estimate is based on the use of a 12

- row plant er set for 30

- inch wide rows. At this setting, the recommended rate of formula application is 3.25 lb per acre. If 180 acres are covered at 3.25 lb per acre with a formulation containing 5% active ingredient (a.i.), then a maximum potential chlorethoxyfo s exposure could amount to 29.25 lb a.i./day. In this study, an average of 45.3 acres were covered per monitoring unit (MU).

Applicator inhalation exposure was monitored with a standard personal air sampling pump (Gilian Model HFS

- 133A) calibrated at a s tandard 2 liters per minute. One such sampler was attached to each worker to collect breathing zone samples during all applicator activities (including outside the enclosed cab), while another identical pump always remained inside the cab collecting sample s.

No measurable dermal residues were found from the monitoring of chlorethoxyfos applicators. All samples were below the level of quantitation (LOQ) for the matrix

used. Calculations used one half the LOQ. Using dermal residue values based on one half of the LOQ for samples of hands, neck/face, lower body and upper body results in a total of 6 ug per

MU. Combining this residue amount with the average amount applied per MU (147 lb formulation, or 7.4 lb a.i.) results in a dermal unit exposure of 0.81 u g a.i./lb a.i. applied.

Estimated Inhalation Chlorethoxyfos Exposure. The average calculated pump filter residue from airborne chlorethoxyfos was 0.06 ug per sample (see table below). When adjusted to a breathing rate of 29 liters per minute (lpm), this residue value results in a total of 0.87 ug per MU ( [0.06 ug  ̧ 2 lpm] x 29 lpm = 0.87 ug). Combining this residue amount with the average amount applied per MU (147 lb formulation, or 7.4 lb a.i.) results in a respiratory unit exposure of 0.12 ug a.i./l b a.i. applied.