UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

Date: September 15, 2015 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

Subject: Tcrbufos. Occupational and Residential Exposure Assessment for the 

Registration Review Risk Assessment. 0420977 

PC Code: I 0500 I 

Decision No.: 472941 

Pelilion No.: NA 

Risk Assessment Type: Occupational/Residential Exposure Assessment 

TXR No.: NA 

M RIO No.: 44 79330 I, 4418040I,4430130 I 

From: Mathew Lloyd, CJH 11.i,-;fl{J Risk Assessment Branch Vil 

Hea lth Effects Division (7509P) 

DP Barcodc: 0420977 

Registration No.: 548 1-545, 548 1-

562 

Regulatory Action: Reg Review 

Case No.: NA 

CAS No.: 13071-79-9 

40 CFR: 180.352 

T hrough: 

~ 

.... :PJJI: Alexandra LaMay, Biologis ! i ~;r-rr Michael S. Metzger, Chief /. L 

Risk Assessment Branch VI · 

Health Effects Division (7509P) 

Introduction 

and /vi / _//~ 

Nancy 

Shalu Shelat

Keller

, 

, 

Indu

Chem

strial 

ist 

Hy

~ 

gienist 

~ 

Exposure Science Advisory Committee (ExpoSAC) I HED 

The Pesticide Reevaluation Division (PRO) requested that the Health Effects Division (HEO) 

conduct an exposure and risk assessment for the currently registered uses of terbufos as part of 

the registration review process. Terbufos is registered for use on corn, sorghum, and sugar beets. 

There are currently no registered non-occupational (residential uses) for terbufos. It is HED 

policy to use the best available data to assess exposure. Several sources of generic data were 

used in this assessment as surrogate data in the absence of chemical-specific data, including 

[Pesticide Handlers Exposure Database Version 1.1 (PHED I. I); and other chemical- and 

scenario-specific exposure monitoring studi es (MRID 44 79330 I, 44180401 , 4430130 l )]. Some 

of these data arc proprietary, and subject to the data protection provisions of the Federal 

Insecticide, Fungicide, and Roclenticidc Act (FIFRA). 

Note: This memorandum was reviewed by the Exposure Science Advisory Committee 

(ExpoSAC) on (07/24/ 14]. 

Page I of29 
Page 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 Residential 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-application Dermal Exposure/Risk Estimates.......................... 21

Appendix A. Summary of Occupational Non-cancer Algorithms............................................... 23

Study Summaries Used in the Occupational Handler Assessment............................................... 26
Page 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:

The only two terbufos end-use formulations 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 an 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 systems. The pre-harvest intervals

(PHI) depend on the crops, and range from 60 days to 150 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 applying). There are no registered residential 

uses associated with terbufos at this time. 

Exposure Duration:

For the organophosphate pesticides (OPs), the match between the toxicological endpoint 

selection and the exposure duration is different than HED’s approach for conventional 

chemicals. The endpoint selection for OPs involves a “single day” and “steady state” approach 

based on an individual chemical’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 considered health protective for commercial occupational handlers that 

apply over longer periods of time (i.e., intermediate-term exposures). Chronic 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 (POD) was selected to assess the 15G terbufos 

formulation from a 28-day dermal toxicity study in rats based on red blood cell (RBC) 

cholinesterase (ChE) inhibition (BMDL10 = 1.04 mg/kg/day; BMD10 = 1.19 mg/kg/day). No 

dermal POD was selected for the 20CR 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 (BMDL10 = 0.01 mg/kg/day; BMD10 = 0.02 mg/kg/day). A total uncertainty factor of 

1000X is appropriate for the dermal route of exposure [10X for interspecies extrapolation, 10X 

for intraspecies variation] and a total uncertainty factor of 3000X is appropriate for the inhalation 

route of exposure [10X for interspecies extrapolation, 10X for intraspecies variation, 30X 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 formulations (15 and 20% ai end use 

products) that are soil incorporated; therefore, a spray drift assessment has not been conducted. 

Occupational Handler Exposure:

HED relies on surrogate data as well as chemical-specific data for the 15% and 20% active 

ingredient granular formulations, 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. An 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 = 

1000; inhalation = 3000). 

Based on the use of engineering controls as defined on the 15G/20G product labels, 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 lbs 

ai/A) where the ARI >1.

The 20% polymer-based active ingredient granular formulation is referenced in this document as 

“20CR.” For the 20CR 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 20CR formulation, therefore, the data were not quantitatively applied to the 

handler assessment for 20CR. The level of concern (LOC) for the inhalation risk estimate is a
Page 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 21 to 80 and 7.9 to 30, 

respectively. Additional qualitative consideration of available exposure data indicates risk 

estimates are of concern for loaders using the 20CR 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., granules 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 treated 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 terbufos because of the application pattern (soil incorporated 

granules with limited potential for worker soil contact). The reentry interval (REI) on the 

currently registered labels (48-72 hours2) 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 registrant-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 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 website3. 

 

2 Depending on geographical meteorological conditions

3 http://www.epa.gov/pesticides/science/handler-exposure-data.html and 

http://www.epa.gov/pesticides/science/post-app-exposure-data.html
Page 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 identifies a number of exposure scenario with risk estimates of 

concern, including all the crop/application rate combinations for loaders with the 15G/20G

products and 20CR product, regardless of the handler data used for the assessment.

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

below 1 using both surrogate4, as well as chemical- and scenario-specific 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 20CR product, risk estimates 

have been calculated for the inhalation route only based on toxicological considerations; risk 

estimates for loaders and applicators are of concern with MOE’s generally below 80 and 30, 

respectively (LOC = 1000). Additional qualitative consideration of available exposure data 

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

A spray drift assessment was not completed for the currently registered uses of terbufos; 

Terbufos end use products are formulated 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 Reevaluation 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 with 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 pattern changes, HED will reevaluate the 

need for a DFR or TTR study, depending on the proposed label change.

 

4 PHED and AHETF
Page 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 within 24 hours. The skin sensitization study was waived for terbufos because of 

the acute lethality.

Table A.2.1 Acute Toxicity Profile - Terbufos

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

870.1100 Acute oral [rat] 00112227 LD50 = 4.5/6.3mg/kg

(signs of ChEI)

I

870.1100 Acute oral [mouse] 00037467 LD50 = 5.0 mg/kg I

870.1100 Acute oral [rat] 00037471 LD50 = 1.3 mg/kg I

870.1100 Acute oral [rat] 00029863 LD50 = 1.5 mg/kg 

(salivation, diuresis, 

diarrhea, disoriented 

locomotion, 

chromadocryorrhea, 

piloerection, body tremors)

I

870.1100 Acute oral [rat] 00035121 LD50 = 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 LD50 = 1.4/3.2 (F/M)

(tremors, salivation, 

exophthalmos, decreased 

activity) 

I

870.1200 Acute dermal [rabbit] 00144806 LD50 = 0.81/0.93mg/kg I

870.1200 Acute dermal [rat] 44021603 LD50 = 123/71 mg/kg

15G formulationA

I

870.1200 Acute dermal [rat] 47512802 LD50 = 71/32 mg/kg

20CR formulationB

I

870.1300 Acute inhalation [rat] 41538101 LC50 = 0. 006 mg/L ♂

LC50 = 0.0012 mg/L 

(salivation, tremors, 

chromodacryorrhea, 

labored breathing, poor 

condition)

I
Page 8 of 29

Table A.2.1 Acute Toxicity Profile - Terbufos

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

ASalivation, chromodacryorrhea, decreased activity, tremors, diuresis, anorexia, lacrimation, prostration

BTremors, decreased activity, ataxia, diuresis, salivation, exophthalmos, dyspnea, dehydration, exophthalmos. 

Toxicological PODs Used for Risk Assessment

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 used in deriving PODs. 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 was selected from the oral range-finding and definitive DNT

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

pups based on RBC and/or brain ChE inhibition (BMDL10 = 0.01 mg/kg/day; BMD10 = 0.02

mg/kg/day). For steady state inhalation exposures, a total uncertainty factor of 3000X was 

applied [10X for interspecies extrapolation, 10X for intraspecies variation and a 30X for 

database uncertainty around the uncertainty regarding the potential neurodevelopmental effects 

of the OPs and because there is an inhalation study requirement for terbufos5.

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 

44520501) in rats based on RBC ChE inhibition (BMDL10 = 1.04 mg/kg/day; BMD10 = 1.19

mg/kg/day) in the male rat. A total uncertainty factor of 1000X is appropriate for dermal 

exposures [10X for interspecies 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 Per HED’s HASPOC review: HASPOC TXR No. 0056967
Page 9 of 29

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 Terbufos

Exposure

Scenario

Point of Departure

(mg/kg/day)

Study and Toxicological

Effects

Dermal

Steady State (21 

days and longer)

[15G]

BMDL10 = 1.04 mg/kg/day

UFA = 10x

UFH = 10x

UFDB = 10x

28-day dermal toxicity study (MRID 44520501) in 

rats

BMD10 = 1.19 mg/kg/day for inhibition of RBC 

cholinesterase in male rats.

Inhalation

Steady State (21 

days and longer)

[both 

formulations]

BMDL10 = 0.01 mg/kg/day

UFA = 10x

UFH = 10x

UFDB = 30x

DNT/RF DNT studies (MRID 46214301; 46240802) 

BMD10 = 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. UFA = extrapolation from animal to 

human (interspecies). UFH = potential variation in sensitivity among members of the human population 

(intraspecies). UFL = use of a LOAEL to extrapolate a NOAEL. UFS = 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 weight 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 

effects. 

4.0 Use Profile 

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

is only applied via soil incorporation. It is classified as Restricted Use and may be purchased 

and used only by certified applicators or persons under their direct supervision. As an 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 RUP 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 long-sleeved shirt and long pants, chemical-resistant gloves, and 

a chemical-resistant apron. Applicators for terbufos applications must use enclosed cabs and 

equivalent handler PPE6. 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

Corn

Field 

corn/pop/sweet 

corn

Atplant/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 nonoccupational (residential) uses of terbufos. Based on the labeled use pattern and the exposure 

profile of terbufos, 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 offtarget and can lead to exposures to those it may directly contact. 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 Rodenticide 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 Volatilization Screening Tool and a 

subsequent Volatilization Screening Analysis7. 

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 task. Job requirements 

(amount of chemical used in each application), the kinds of equipment used, the target being 

treated, and the level of protection used by a handler can cause exposure levels to differ in a 

manner specific to each application event. 

 

7 Available: http://www.regulations.gov/#!docketDetail;D=EPA-HQ-OPP-2014-0219
Page 12 of 29

The occupational handler assessment for terbufos relies on both PHED-based as well as 

chemical- and scenario-specific data to address loader and applicator risk estimates. Appendix B 

summarizes the occupational exposure and risk characterization associated 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 terbufos. 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) include:

 loading granular formulations8(PHED data – Engineering Controls);

 loading 15G/20G formulation in “Lock-N-Load” packaging (completed using chemicaland scenario-specific data);

 loading 15G/20G formulation in “Smartbox” packaging (completed using scenariospecific data);

 applying granular formulations9using 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 Smartbox planters 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 assumption 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 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 Surrogate Reference Table9”, 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 website10. 

 

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

9 Available: http://www.epa.gov/opp00001/science/handler-exposure-table.pdf

10 Available: http://www.epa.gov/pesticides/science/handler-exposure-data.html
Page 13 of 29

The unit exposures associated with the chemical specific data referenced above has been used 

and described extensively in past HED risk assessments11. The available chemical- and scenariospecific data has been reassessed and quantitatively incorporated into this assessment where 

possible12.

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

Source1 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 scenariospecific 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 Exposure Data Review “Occupational Exposure and Risk Assessment 

for Loaders and Applicators Handling Terbufos Products and Supporting Worker Exposure Studies” D422600”
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). 

 

Exposure 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 pressure 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 conventional chemicals. The endpoint selection for organophosphate pesticides 

involves a “single day” and “steady state” approach based on an individual chemical’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 

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 product over a period of 

weeks (e.g. completing multiple applications for multiple 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 RED required engineering controls such as closed 

cabs and closed mixing/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 since the LOC values 

for dermal exposure (1000) and inhalation exposure (3000) 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 20CR product, risk estimates are not combined for the dermal and inhalation routes of 

exposure. Based on the 20CR formulation specific dermal study not identifying cholinesterase 

inhibition, only quantitative inhalation 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 chemicalspecific data set is quantitatively incorporated into the occupational handler risk estimation of the 
Page 15 of 29

15G/20G product, but not the 20CR 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 inhalation risk estimates for the 20CR product.

15G/20G Risk Estimates 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:

Based 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 applicators, with ARIs

less than 1 for all crop application rates and scenarios for both loaders and applicators. The target 

ARI is 1; therefore, ARIs of less than 1 are risk estimates of concern. ARI’s range from 0.004 to 

0.02 for loaders and 0.002 to 0.01 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 chemical-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 wholebody dosimeters showed detectable 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 used 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 0.036 to 0.18 for loaders and 0.27 to 1.4 for applicators. Using the chemicalspecific data available, occupational 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 studies 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 appropriate match for the currently registered terbufos products (15G/20G). 

ARI’s range from 0.01 to 0.61 for loaders and 0.004 to 0.018 for applicators. Using the scenariospecific data available, occupational handler risk estimates are of concern (i.e., ARIs <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 

Rate2

Area 

Treated or 

Amount 

Handled 

Daily3

Dermal Inhalation Total

Mitigation 

Level 

(Engineering 

Controls)

Mitigation Level

(Engineering 

Controls)

Dose 

(mg/kg/day)4 MOE5 Dose (mg/kg/day)6 MOE7 ARI8

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

ChemSpecific B 0.074 0.0118 0.000112 9300 0.0000178 560 0.18

SmartboxC 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

ChemSpecific B 0.074 0.0118 0.000278 3700 0.0000445 220 0.072

SmartboxC 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

ChemSpecific B 0.074 0.0118 0.000365 2800 0.0000581 170 0.056

SmartboxC 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

ChemSpecific B 0.074 0.0118 0.000423 2500 0.0000674 150 0.049

SmartboxC 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

ChemSpecific B 0.074 0.0118 0.000223 4700 0.0000355 280 0.092

SmartboxC 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

ChemSpecific B 0.074 0.0118 0.000558 1900 0.000089 110 0.036

SmartboxC 0.2 0.003 0.00151 690 0.0000226 440 0.12
Page 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 

Rate2

Area 

Treated or 

Amount 

Handled 

Daily3

Dermal Inhalation Total

Mitigation 

Level 

(Engineering 

Controls)

Mitigation Level

(Engineering 

Controls)

Dose 

(mg/kg/day)4 MOE5 Dose (mg/kg/day)6 MOE7 ARI8

Applicator

Ground Application Sweet corn

PHED A 2.1A 0.22A

1.3 80 A/day

0.00301 350 0.000332 30 0.0097

ChemSpecific B 0.0485B 0.00146B 0.000073 14000 0.0000022 4500 1.4

SmartboxC 0.12 0.81 0.00122 850 0.000181 55 0.018

Ground Application Field corn

PHED A 2.1A 0.22A

1.7 200 A/day

0.00986 110 0.00108 9.3 0.003

ChemSpecific B 0.0485B 0.00146B 0.000239 4400 0.00000719 1400 0.42

SmartboxC 0.12 0.81 0.00399 260 0.000591 17 0.0055

Ground Application Field corn

PHED A 2.1A 0.22A

1.97 200 A/day

0.0114 91 0.00126 7.9 0.0026

ChemSpecific B 0.0485B 0.00146B 0.000277 3800 0.00000833 1200 0.36

SmartboxC 0.12 0.81 0.00462 230 0.000686 15 0.0049

Ground Application Sweet corn 

- SLN

PHED A 2.1A 0.22A

2.6 80 A/day

0.00603 170 0.000664 15 0.0049

ChemSpecific B 0.0485B 0.00146B 0.000146 7100 0.00000441 2300 0.69

SmartboxC 0.12 0.81 0.00243 430 0.000362 28 0.0091

Ground Application Field corn -

SLN

PHED A 2.1A 0.22A

2.6 200 A/day

0.0151 69 0.00165 6.1 0.002

ChemSpecific B 0.0485B 0.00146B 0.000365 2800 0.000011 910 0.27

SmartboxC 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 441804-01/443013-01]

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

20CR Risk Estimate and Characterization

Table 6.1.2 identifies risk estimates for HED’s PHED-based inhalation exposure assessment for 

the 20CR terbufos product. 

PHED-Based Assessment:

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

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

estimates ranging from 21 to 80 for loaders and 7.9-30 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 cholinesterase 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 granular 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 assessment. 

Incorporating Chemical-specific Data:

As discussed above in Section 6.1, the chemical-specific data for the 20CR formulation of 

terbufos was not used quantitatively used in the occupational handler assessment. However, the 

20CR portion of the chemical-specific exposure study is useful for qualitatively comparing the 

exposure profiles of the two available terbufos formulations. An important aspect of 

characterization is that the 20G formulation is based in a polymer matrix and presents 

significantly 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. 

Risk 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 110-560, depending on the exposure scenario. Route-specific inhalation MOEs for 

applicators range from 910-4500, depending on the exposure scenario. 
Page 20 of 29

Table 6.1.2. Steady-State Occupational Exposure and Risk Estimates for Terbufos (20CR). 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 

Rate2

Area 

Treated or 

Amount 

Handled 

Daily3

Inhalation

Mitigation Level

(Engineering 

Controls)

Mitigation Level

(Engineering 

Controls)

Dose 

(mg/kg/day)4 MOE5

Loader

Loader – ground based 

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

Loader – ground based 

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

Loader – ground based 

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

Loader – ground based 

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

Applicator

Ground Application

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

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

Ground Application Field corn N/A 0.22A 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 reentry 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 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 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 

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 

(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-HQOPP-2014-0219). 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. 

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 pesticides outdoors is likely to result in 

higher exposure than post-application exposure.

6.2.2 Occupational 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 the 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 uses 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 for 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 exposure. Therefore, the [156 subpart K] Worker Protection 

Statement interim REI of 48/72 hours is adequate to protect agricultural workers from postapplication exposures to terbufos. 
Page 23 of 29

Appendix A. Summary of Occupational Non-cancer Algorithms

Occupational 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

where:

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)

where:

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 (%), 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 

handlers were compared to the appropriate POD (i.e. BMDL10) to assess the risk to occupational 

handlers for each exposure route. All MOE values were calculated using the following formula:

MOE = POD (typically a BMDL10 in mg/kg/day) 

ADD (mg/kg/day)

where:

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 

(20CR)

Comments

Dermal Inhalation Combined* Dermal Inhalation Combined*

Loader 

(PHEDbased) 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 claybased surrogate 

chemical UE

Loader 

(chemicalspecific)

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 20CR

has a lower

exposure 

potential

Loader 

(scenariospecific) 

[SmartBox®]

Y Y Y - ARI

Equipmentspecific closed 

loading study –

not chemicalspecific but 

applicable via 

data bridging

N N N

Terbufos is 

available for 

SmartBox®

application with 

the 15/20G 

formulation

Applicator 

(PHEDbased) 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 claybased surrogate 

chemical UE
Page 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 

(20CR)

Comments

Dermal Inhalation Combined* Dermal Inhalation Combined*

Applicator 

(chemicalspecific)

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 20CR

has a lower

exposure 

potential

Applicator 

(scenariospecific) 

[SmartBox®]

Y Y Y - ARI

Equipmentspecific closed 

loading study –

not chemicalspecific 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 Approach
Page 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 Reregistration 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 and 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 equipment/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 in 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 tractors (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 ranged 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 pumps, 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 monitoring data were used in the risk assessment. These data were not used 

 

13 Chemical-specific data review: Lloyd, “Unit Exposure Calculations and Summary for “Occupational 

Exposure and Risk Assessment for Loaders and Applicators Handling Terbufos Products and Supporting Worker 

Exposure Studies” D422600
Page 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 described 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 described 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 quantification (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 generally 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 exposure 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 requirements 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 the avaialable chemical-specific data, two non-chemical specific exposure studies 

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® technology for 

the mixing/loading of granular formulations for aerial and ground applications of 

Chlorethoxyfos, and the application by ground equipment. Separate data evaluation records 
Page 28 of 29

(DERs) were completed for the mixing/loading[1] and applicator[2] studies; 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 During 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 preparing 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 cycle 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 loader 

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 below 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. Individual 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 MRID: 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 the 

typical corn-planting season in the midwestern corn belt (mid-April 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 addition, under their work 

clothes, each applicator wore a long-sleeved t-shirt and ankle-length underwear tights as wholebody 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 planter 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 chlorethoxyfos 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 standard 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 samples.

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 ug 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./lb a.i. applied.