Date: 

Subj ect: 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

l 5-SEP-2015 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

Profenofos. Occupational and Residential Exposure and Risk Assessment for 

Registration Review. 

PC Code: 111401 DP Barcode: 0427268 

Registration Number: NIA 

Regulatory Action: NIA 

Case Number: 2540 

Decision Numbe r: 482022 

Pe tition Number: NA 

Risk Assessment Type: NA 

TXR Number: NA C AS Number: 41198-08-7 

MRID Numbers: NA 40CFR: § 180.404 

From: 

Through: 

To: 

Introduction 

Kelly 

Risk Assessment 

M. Lowe, E

Branch 

nvironmental 

I (RAB 

Sc

1) 

ientist /?~~ 

, 

Health Effects Division (HED; 7509P) /'J # ll.1 / r 

Thurston Morton, Acting Branch Chief ( j/J . rv 

HED (7509P) 

and 

Matthew Crowley, Reviewer ~ J---·- Shalu Shelat, Reviewer '1\f ~ ~hl.-4---

Exposure Science Advisory Committee (ExpoSAC) I HED 

Christina Scheltema 

Patricia Parrott 

Pesticide Re-Evaluation Division (PRD) (7508P) 

As part of Registration Review, the Pesticide Re-evaluation Division (PRD) of OPP has 

requested that HED evaluate the hazard and exposure data and conduct occupational and 

residential exposure assessments, as needed, to estimate the risk to human health that will result 

from the currently registered uses of pesticides. This memorandum serves as HED's 

Registration Review assessment of the occupational and residential handler and post-application 

exposure and risk from the currently registered uses of profenofos. 

Page I of35 
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 1.1 ); the Agricultural 

Handler Exposure Task Force (AHETF) database; and the Agricultural Reentry Task Force 

(ARTF) database. Some of these data are proprietary, and subject to the data protection 

provisions of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). 

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

(ExpoSAC) on 02-APR-2015. 

Page 2 of35 
Page 3 of 35

Table of Contents

1.0 Executive Summary............................................................................................................. 4

2.0 Risk Assessment Conclusions and Recommendations........................................................ 7

2.1 Summary of Risk Estimates............................................................................................. 7

2.2 Label Recommendations.................................................................................................. 7

2.3 Data Deficiencies and Requirements ............................................................................... 7

3.0 Hazard Characterization....................................................................................................... 7

4.0 Exposure and Use Profile................................................................................................... 11

5.0 Residential Exposure and Risk Estimates.......................................................................... 12

5.1 Spray Drift...................................................................................................................... 12

5.2 Residential Bystander Post-Application Inhalation Exposure ....................................... 16

6.0 Occupational Exposure and Risk Estimates ...................................................................... 16

6.1 Occupational Handler Exposure/Risk Estimates............................................................ 16

6.2 Occupational Post-application Exposure/Risk Estimates .............................................. 20

6.2.1 Occupational Post-application Inhalation Exposure/Risk Estimates...................... 20

6.2.2 Occupational Post-application Dermal Exposure/Risk Estimates.......................... 20

Appendix A. Summary of Occupational and Residential Non-cancer Algorithms..................... 26

Appendix B. Summary of Available DFR Data for Profenofos.................................................. 28
Page 4 of 35

1.0 Executive Summary

Profenofos, [O-(4-bromo-2-chlorophenyl) O-ethyl S-propyl phosphorothioate], is an 

organophosphate (OP) insecticide-miticide used for insect and mite control on cotton. This 

document assesses exposures and risk estimates from the registered use of profenofos required 

during Registration Review. There are currently no registered residential uses. There is the 

potential for non-occupational exposure as a result of spray drift.

Use and Exposure Profile

There is only one end-use product label registered with profenofos as the active ingredient (ai)

(EPA Reg. #100-669; Curacron® 8E Insecticide-Miticide). This product is formulated as an 

emulsifiable concentrate (EC), containing 73% ai or 8 lb ai/gallon, and is a restricted use 

pesticide. The product label indicates that a closed mixing/loading system and enclosed cab 

groundboom equipment are required. The maximum single application rate is 0.5 lb ai/A. The 

maximum seasonal rate is 5 lb ai/A/season, with a 5 day minimum retreatment interval (RTI). 

Based on the registered use pattern for profenofos, dermal and inhalation exposures are 

anticipated for occupational handlers and post-application workers. The Curacron® 8E product 

label indicates that a closed mixing/loading system and enclosed cab are required. Mixer, 

loaders, applicators, and other handlers using a closed system must also wear long sleeved shirt, 

long pants, shoes plus socks, chemical-resistant gloves, chemical-resistant apron (for mixing and 

loading), and protective eyewear. The label recommends a restricted entry interval (REI) of 48 

hours (72 hours in areas where rainfall is less than 25 inches per year). As noted above, there are 

currently no registered residential uses; however, there is the potential for non-occupational 

exposure (dermal and incidental oral) as a result of spray drift. 

Hazard Profile and Dose Response 

Profenofos is classified as acutely toxic via the oral (Toxicity Category II) and dermal routes 

(Toxicity Category I or II) and classified as having low acute toxicity via the inhalation route 

(Toxicity Category IV). It was found to be a minimal eye irritant and moderate dermal irritant

(Toxicity Category III). It was also found to be a dermal sensitizer.

Profenofos 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 points of 

departure (PODs). Profenofos, as the parent ai, is an acetylcholinesterase (AChE) inhibiting 

chemical. Profenofos has high quality dose response data across multiple lifestages, durations, 

and routes for both red blood cell (RBC) and brain AChE inhibition. RBC AChE inhibition was 

similar or more sensitive than the brain AChE inhibition across most studies, durations, 

lifestages, and routes. For human health risk assessment, studies have been evaluated using 

benchmark dose (BMD) modeling techniques. Available studies with adult animals show similar 

findings in gavage and dietary studies. Studies via the dermal and inhalation routes allow for 

route-specific evaluation. 

The steady-state dermal POD was selected from a 21-day dermal toxicity study in rabbits based 

on RBC AChE inhibition. However, the data were not amenable to BMD modeling; therefore 
Page 5 of 35

the no observed adverse effect level (NOAEL) of 1 mg/kg/day was selected as the POD for 

dermal exposures. The lowest observed adverse effect level (LOAEL) was 10 mg/kg/day. 

The steady-state inhalation POD was selected from 21-day inhalation toxicity study based on 

RBC AChE inhibition. The data were not amenable to BMD modeling; therefore, the LOAEL of 

68 mg/m3 was selected as the POD for inhalation exposures. The NOAEL was not established. 

For occupational scenarios, duration adjustments were made to extrapolate exposure in the 

animal study (6 hours/day, 5 days/week) to a typical occupational exposure (8 hours/day, 5 

days/week). The resulting duration adjusted value for occupational exposures is 51 mg/m3. For 

estimating occupational inhalation risks from different occupational activities, inhalation doses 

corresponding to the breathing rates for each activity (8.3, 16.7, or 29 L/min) were calculated 

using this duration adjusted value; 2.90, 5.84, and 10.14 mg/kg/day, respectively. 

For residential incidental oral and dermal scenarios, a total uncertainty factor of 1000X was 

applied (10X for interspecies extrapolation, 10X for intraspecies variation, and a 10X FQPA 

safety factor due to uncertainty in the human dose-response relationship for neurodevelopmental 

effects1). For occupational dermal scenarios, a total uncertainty factor of 1000X was applied 

(10X for interspecies extrapolation, 10X for intraspecies variation, and a 10X database 

uncertainty factor due to uncertainty in the human dose-response relationship for 

neurodevelopmental effects). For occupational inhalation scenarios, a total uncertainty factor of 

3000X was applied (10X for interspecies extrapolation, 10X for intraspecies variation, and a 30X 

database uncertainty factor incorporating uncertainty in the human dose-response relationship for 

neurodevelopmental effects and the uncertainty due to lack of a NOAEL in the subchronic 

inhalation toxicity study). Resulting occupational dermal and inhalation risk estimates were 

combined using the aggregated risk index (ARI) approach since the same effects were observed 

for both routes of exposure (RBC AChE inhibition), but the levels of concern (LOCs) are 

different. Residential post-application dermal and incidental oral risk estimates were also 

combined since the same effects were observed for both routes of exposure (RBC AChE 

inhibition). 

Profenofos is classified as a “Group E Chemical – evidence of non-carcinogenicity for humans” 

based on lack of evidence of carcinogenicity in rats and mice. A quantitative cancer risk 

assessment is not required.

Residential Exposure and Risk

There are currently no registered residential uses of profenofos; therefore a quantitative 

residential handler and post-application assessment was not conducted. 

Spray drift

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

profenofos. Risk estimates related to spray drift are of concern at various distances from the 

edge of the field for adults and children (1 to <2 years) depending on the spray drift scenario. 

For adults, the screening level scenario of a high boom and very fine to fine spray requires a 

distance of over 300 feet to reach a dermal MOE ≥ 1000. For children, the screening level 

scenario also requires a distance of over 300 feet to reach a combined (dermal and incidental 

oral) MOE ≥1000. Drift reduction technologies, such as using coarser sprays and lowering boom 

 

1 For more details, see Section 4.4 in the human health risk assessment: Memo, M. Perron et al, 15-SEP-2015, D416010.
Page 6 of 35

height for groundboom sprayers, reduces risk concerns; however, there are still risk estimates of 

concern at the field edge. 

 

Occupational Exposure and Risk

Occupational handler dermal and inhalation exposure and risk estimates were calculated for the 

registered uses of profenofos. The occupational handler exposure and risk estimates indicate that

the steady-state dermal and inhalation combined ARIs are of concern to HED (i.e., ARI ≤ 1) for

all scenarios. 

Occupational post-application dermal exposure and risk estimates were assessed for the

registered cotton use of profenofos using submitted chemical-specific dislodgeable foliar residue 

(DFR) data and dislodgeable cotton boll data. Based on the current exposure assessment, postapplication risk estimates remain a concern (i.e., MOEs < 1000) up to 4 days after application for 

hand weeding and up to 9 days after application for scouting. Post-application risk estimates 

associated with harvesting activities are a concern (MOEs < 1000) 14 days after treatment, which 

would be the earliest harvesting could occur after application based on the current pre-harvest 

interval (PHI). An additional calculation was performed to estimate post-application exposure 

and risk using the cotton boll residue data from the day of sampling (day 44); however, there 

were still risk estimates of concern for all harvesting activities even 44 days after application at 

which point residue values were less than the limit of quantification (LOQ) in the study. 

 

The current product-label restricted entry interval (REI) is specified as 48 hours (72 hours in 

areas that receive less than 25 inches of rain per year). The REI on the registered label is in line 

with the Worker Protection Standard [40 CFR 156.208(c)(2)] assignments for ai’s that are

classified as Toxicity Category I for acute dermal, eye irritation, or primary skin irritation, and 

for organophosphates in particular. However, there were risk estimates of concern related to all 

activities associated with cotton at the current label-prescribed REI.

Based on the Agency's current practices, a quantitative non-cancer occupational post-application 

inhalation exposure assessment was not performed for profenofos 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 profenofos.

Human Studies Review

This risk assessment relies in part on data from studies in which adult human subjects were

intentionally exposed to a pesticide or other chemical. These data, which include studies from 

the PHED 1.1, the AHETF database, and the ARTF database are (1) subject to ethics review 

pursuant to 40 CFR 26, (2) have received that review, and (3) are compliant with applicable 

ethics requirements. For certain studies, the ethics review may have included review by the 

Human Studies Review Board. Descriptions of data sources, as well as guidance on their use, 

can be found at the Agency website2. 

 

2 http://www.epa.gov/pesticides/science/handler-exposure-data.html and http://www.epa.gov/pesticides/science/post-appexposure-data.html
Page 7 of 35

2.0 Risk Assessment Conclusions and Recommendations

2.1 Summary of Risk Estimates

 The occupational handler exposure and risk estimates indicate that the steady-state 

dermal and inhalation combined ARIs are of concern to HED (i.e., ARI ≤ 1) using closed 

systems for mixing/loading and applying. ARIs range from 0.08 to 0.14 using HED 

defaults for area treated per day, and from 0.1 to 0.17 using an adjusted area treated per 

day to account for a label restriction on the maximum amount of ai that can be handled 

per day. 

 Occupational post-application dermal exposure and risk estimates are a concern for all 

activities associated with cotton. A REI of 4 days is necessary to reach acceptable MOEs 

(i.e., MOEs ≥ 1000) for hand weeding and a REI of 9 days is necessary for scouting. 

Activities associated with harvesting do not reach acceptable MOEs up to 44 days after 

treatment.

 Risk estimates related to spray drift are of concern at various distances from the edge of 

the field for adults and children (1 to <2 years) depending on the spray drift scenario. For 

adults, the screening level scenario of a high boom and very fine to fine spray requires a 

distance of over 300 feet to reach a dermal MOE ≥ 1000. For children, the screening 

level scenario also requires a distance of over 300 feet to reach a combined (dermal and

incidental oral) MOE ≥1000. Drift reduction technologies, such as using coarser sprays 

and lowering boom height for groundboom sprayers, reduces risk concerns; however, 

there are still risk estimates of concern at the field edge.

2.2 Label Recommendations 

No label recommendations have been identified. A summary of the risk estimates has been 

provided, and shows that there are risk estimates of concern for registered uses of profenofos 

based on the label-required personal protective equipment (i.e., engineering controls) and 

restricted entry intervals (REIs).

2.3 Data Deficiencies and Requirements

There are no data deficiencies for profenofos at this time related to non-dietary exposure.

3.0 Hazard Characterization

Profenofos is classified as acutely toxic via the oral (Toxicity Category II) and dermal routes 

(Toxicity Category I or II) and classified as having low acute toxicity via the inhalation route 

(Toxicity Category IV). It was found to be a minimal eye irritant and moderate dermal irritant 

(Toxicity Category III). It was also found to be a dermal sensitizer. Table 3.0.1 provides a 

summary of the acute toxicity of profenofos.
Page 8 of 35

Table 3.0.1. Acute Toxicity Profile for Technical Profenofos.

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

870.1100 Acute oral (rat) 41714801

LD50 = Males: 492 (363-666) mg/kg

 Females: 809 (600-1090) mg/kg

 Combined: 630 mg/kg

II

870.1100 Acute oral (mouse) 00105226 LD50 = 298 (268-332) mg/kg II

870.1100 Acute oral (rabbit) 00105228 LD50 = 300 mg/kg II

870.1200 Acute dermal (rat) 00105231 LD50 = 1610 (1073-2415) mg/kg II

870.1200 Acute dermal (rabbit) 00109427

LD50 = Intact skin –

 Males: 146.8 mg/kg

 Females: 143.4 mg/kg

 Abraded skin-

 Males: 97.5 mg/kg

 Females: 15.9 mg/kg

I

870.1300 Acute inhalation (rat) 00109428 LC50 = 3.36 mg/L IV

870.2400 Acute eye irritation 

(rabbit) 00109429 Minimal irritation, reversible within 7 days; no corneal opacity III

870.2500 Acute dermal irritation 

(rabbit) 41714802 Moderately irritating at 72 hours III

870.2600 Skin sensitization 

(guinea pig) 00109431 Sensitization was induced -

Profenofos is an OP with a neurotoxic AOP; neurotoxicity is the most sensitive effect in all 

species, routes, and lifestages, and is being used in deriving PODs. Profenofos, as the parent 

active ingredient, is an AChE inhibiting chemical. Profenofos has high quality dose response 

data across multiple lifestages, durations, and routes for both RBC and brain AChE inhibition. 

RBC AChE inhibition was similar or more sensitive than the brain AChE inhibition across most 

studies, durations, lifestages, and routes. For human health risk assessment, studies have been 

evaluated using BMD modeling techniques. Available studies with adult animals show similar 

findings in gavage and dietary studies. Studies via the dermal and inhalation routes allow for 

route-specific evaluation. 

OPs exhibit a phenomenon known as steady state AChE inhibition. After repeated exposure at 

the same dose, the degree of inhibition comes into equilibrium with the production of new, 

uninhibited enzyme. At this point, the amount of AChE inhibition at a given dose remains 

consistent across duration. In general, OPs reach steady state within 2-3 weeks, but this can vary 

among OPs. In the case of profenofos, the pattern of steady state is reached at or near 10 days of 

exposure. In addition to the consistency across durations, the data across multiple repeat dosing 

studies in rats are similar. For the purposes of the occupational and residential risk assessment, 

only the steady-state duration is relevant to the exposure scenarios.

Consistent with risk assessments for other AChE-inhibiting compounds, OPP has used a 

benchmark response (BMR) level of 10%, and has thus calculated BMD10 and BMDL10 values. 

The BMD10 is the estimated dose where AChE is inhibited by 10% compared to background. 
Page 9 of 35

The BMDL10 is the lower confidence bound on the BMD10. As a matter of science policy, the 

Agency uses the BMDL, not the BMD, for use as the POD (USEPA, 20123). 

The steady-state incidental oral POD (BMDL10 = 0.12 mg/kg; both sexes) was selected from the 

rat combined chronic/carcinogenicity study (13 week interim measurement). The corresponding 

BMD10 was 0.14 mg/kg and 0.13 mg/kg in males and females, respectively, based on RBC 

AChE inhibition.

The steady-state dermal POD was selected from a 21-day dermal toxicity study in rabbits based 

on RBC AChE inhibition. However, the data were not amenable to BMD modeling4; therefore 

the NOAEL of 1 mg/kg/day was selected as the POD for dermal exposures. The LOAEL was 10 

mg/kg/day. 

The steady-state inhalation POD was selected from 21-day inhalation toxicity study based on 

RBC AChE inhibition. The data were not amenable to BMD modeling5; therefore, the LOAEL 

of 68 mg/m3 was selected as the POD for inhalation exposures. The NOAEL was not 

established. Due to insufficient characterization of particle sizes in the study, the mass median 

aerodynamic diameter (MMAD) and geometric standard deviation (GSD) could not be 

determined. As a result, human equivalent concentrations could not be estimated for the 

systemic effects (AChE inhibition) from inhalation exposure. For occupational scenarios, 

duration adjustments were made to extrapolate exposure in the animal study (6 hours/day, 5 

days/week) to a typical occupational exposure (8 hours/day, 5 days/week). The resulting 

duration adjusted value for occupational exposures is 51 mg/m3. For estimating occupational 

inhalation risks from different occupational activities, inhalation doses corresponding to the 

breathing rates for each activity (8.3, 16.7, or 29 L/min) were calculated using this duration 

adjusted value; 2.90, 5.84, and 10.14 mg/kg/day, respectively. 

For residential incidental oral and dermal scenarios, a total uncertainty factor of 1000X was 

applied (10X for interspecies extrapolation, 10X for intraspecies variation, and a 10X FQPA 

safety factor due to uncertainty in the human dose-response relationship for neurodevelopmental 

effects6). For occupational dermal scenarios, a total uncertainty factor of 1000X was applied 

(10X for interspecies extrapolation, 10X for intraspecies variation, and a 10X database 

uncertainty factor due to uncertainty in the human dose-response relationship for 

neurodevelopmental effects). For occupational inhalation scenarios, a total uncertainty factor of 

3000X was applied (10X for interspecies extrapolation, 10X for intraspecies variation, and a 30X 

database uncertainty factor incorporating uncertainty in the human dose-response relationship for 

neurodevelopmental effects and the uncertainty due to lack of a NOAEL in the subchronic 

inhalation toxicity study).

 

3 USEPA (U.S. Environmental Protection Agency). 2012. Benchmark Dose Technical 

Guidance. http://www.epa.gov/raf/publications/pdfs/benchmark_dose_guidance.pdf

4 Data were not amenable to BMD modeling due to a flat dose response with a decrease only at the highest dose tested and 

relatively large variability noted at all doses.

5 Mortality at the highest dose tested left only two treatment groups for modeling and dose selection forced extrapolation to a

much lower value from the lowest dose to obtain a BMD10.

6 For more details, see Section 4.4 in the human health risk assessment: Memo, M. Perron et al, 15-SEP-2015, D416010.
Page 10 of 35

Profenofos is classified as a “Group E Chemical – evidence of non-carcinogenicity for humans” 

based on lack of evidence of carcinogenicity in rats and mice. A quantitative cancer risk 

assessment is not required.

Table 3.0.2. Summary of Toxicological Doses and Endpoints for Profenofos for Use in Human Health Risk 

Assessments.

Exposure/

Scenario

Point of 

Departure 

(POD)

Uncertainty 

Factorsa

Level of Concern

(LOC) Study and Toxicological Effects

Incidental Oral

Steady State

BMDL10 = 

0.12 mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 

10X

Residential LOC for 

MOE = 1000

Combined chronic oral 

toxicity/carcinogenicity study 

(MRID 00081685)

BMD10 = 0.14/0.13 mg/kg/day 

(males/females)

Inhibition of RBC AChE in adult rats at 13 

week interim measurement.

Dermal Steady 

State

NOAEL = 

1 mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF / 

UFDB = 10x

Occupational / 

Residential LOC for 

MOE = 1000

21-day rabbit dermal toxicity 

(MRID 41644501)

LOAEL = 10 mg/kg/day

Inhibition of RBC AChE in adult rats.

Inhalation 

Steady State

LOAEL =

68 mg/m3/daya

UFA = 10X

UFH = 10X

UFDB = 30x

Occupational LOC for 

MOE = 3000

21-day inhalation rat study

(MRID 00082079)

LOAEL = 68 mg/m3/day

Inhibition of RBC AChE in adult rats.

Cancer (oral, 

dermal, 

inhalation)

Classification: Group E Chemical – Not likely to be carcinogenic to humans

a. For residential incidental oral and dermal scenarios, FQPA SF retained for infants, children, youths, and women of 

childbearing age for all exposure scenarios due to uncertainty in the human dose-response relationship for 

neurodevelopmental effects (see Section 4.4 of the human health risk assessment, D416010). For occupational dermal 

scenarios, UFDB = database uncertainty factor for uncertainty in the human dose-response relationship for 

neurodevelopmental effects (see Section 4.4 of the human health risk assessment, D416010). For occupational 

inhalation scenarios, UFDB = database uncertainty factor incorporating uncertainty in the human dose-response 

relationship for neurodevelopmental effects (see Section 4.4 of the human health risk assessment, D416010) and the 

UFL due to lack of a NOAEL in the subchronic inhalation toxicity study.

b. Inhalation doses corresponding to the breathing rates of 8.3, 16.7, and 29 L/min were calculated as 2.90, 5.84, and 

10.14 mg/kg/day, respectively, for occupational activities using a duration adjusted value of 51 mg/m3.

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. UF = uncertainty factor. UFA = extrapolation 

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

(intraspecies). MOE = margin of exposure. LOC = level of concern. BMD = benchmark dose. BMDL = lower 95% confidence 

interval for benchmark dose. 

Absorption: Since the dermal and inhalation PODs were based on route-specific toxicity studies, 

absorption factors were not necessary to estimate exposure. 

Body Weight: For adults, when an endpoint is not sex-specific (i.e., the endpoints are not based 

on developmental or fetal effects) a body weight of 80 kg is typically used in risk assessment; 
Page 11 of 35

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 effects7. A body weight of 11 kg was used to assess exposure to children 

(1 to <2 years old) from spray drift.

4.0 Exposure and Use Profile 

There is only one end-use product label registered with profenofos as the ai (EPA Reg. #100-

669; Curacron® 8E Insecticide-Miticide). This product is formulated as an EC, containing 73% 

ai or 8 lb ai/gallon, and is a restricted use pesticide. The product label indicates that a closed 

mixing/loading system and enclosed cab groundboom equipment are required. The maximum 

single application rate is 0.5 lb ai/A. The maximum seasonal rate is 5 lb ai/A/season, with a 5 

day minimum RTI. 

Based on the registered use pattern for profenofos, dermal and inhalation exposures are 

anticipated for occupational handlers and post-application workers. The Curacron® 8E product 

label indicates that a closed mixing/loading system and enclosed cab are required. Mixer, 

loaders, applicators, and other handlers using a closed system must also wear long sleeved shirt, 

long pants, shoes plus socks, chemical-resistant gloves, chemical-resistant apron (for mixing and 

loading), and protective eyewear. The label recommends a REI of 48 hours (72 hours in areas 

where rainfall is less than 25 inches per year). As noted above, there are currently no registered 

residential uses; however, there is the potential for non-occupational exposure (dermal and 

incidental oral) as a result of spray drift. 

Table 4.1. Summary of Registered Use Directions for Profenofos.

Application 

Timing, Type, 

and Equip.

Formulation 

[EPA Reg. No.]

Maximum 

Application 

Rate

Max No. 

Applications 

per Season

Max Seasonal 

Application 

Rate

Use Directions and Limitations

Cotton

Enclosed cab 

Groundboom

Make 1st

application 

when pest 

populations 

reach 

economic 

thresholds

Emulsifiable 

Concentrate

100-669

73%ai

8 lb ai/gal

Curacron® 8E 

InsecticideMiticide

0.5 pt 

product/A

0.5 lb ai/A

Based on max 

single rate and 

max seasonal 

rate, up to 10 

applications 

per season (not 

specified on 

label).

5 pt/A/season

5 lb 

ai/A/season

 Restricted Use Pesticide

 Closed system mixing and 

loading and enclosed tractor 

cab required

 REI = 48 hours (72 hours in 

areas that receive 25 inches or 

less of rain)

 Do not apply by aerial or 

chemigation application

 Loaders/mixers not allowed to 

handler more than 10 

gallons/day

 Hand harvesting is prohibited

 Repeat applications at 5-7 

days intervals as needed

 Apply in minimum of 5 

gallons/A

 Pre-harvest Interval (PHI) = 

14 days when diluted with 

water; 30 days when diluted 

 

7 For more details, see Section 4.4 in the human health risk assessment: Memo, M. Perron et al, 15-SEP-2015, D416010.
Page 12 of 35

Table 4.1. Summary of Registered Use Directions for Profenofos.

Application 

Timing, Type, 

and Equip.

Formulation 

[EPA Reg. No.]

Maximum 

Application 

Rate

Max No. 

Applications 

per Season

Max Seasonal 

Application 

Rate

Use Directions and Limitations

with oil.

5.0 Residential Exposure and Risk Estimates

There are no residential uses currently registered for profenofos; therefore, a quantitative 

residential handler and post-application assessment was not conducted.

6.0 Non-Occupational Spray Drift Exposure and Risk Estimates

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. They can also deposit on 

surfaces where contact with residues can eventually lead to indirect exposures (e.g., children 

playing on lawns where residues have deposited next to treated fields). The potential risk 

estimates from these residues can be calculated using drift modeling onto 50 feet wide lawns 

coupled with methods employed for residential risk assessments for turf products.

The approach to be used for quantitatively incorporating spray drift into risk assessment is based 

on a premise of compliant applications which, by definition, should not result in direct exposures 

to individuals because of existing label language and other regulatory requirements intended to 

prevent them.8 Direct exposures would include inhalation of the spray plume or being sprayed 

directly. Rather, the exposures addressed here are thought to occur indirectly through contact 

with impacted areas, such as residential lawns, when compliant applications are conducted. 

Given this premise, exposures for children (1 to <2 years old) and adults who have contact with 

turf where residues are assumed to have deposited via spray drift thus resulting in an indirect 

exposure are the focus of this analysis analogous to how exposures to turf products are 

considered in risk assessment. 

In order to evaluate the drift potential and associated risks, an approach based on drift modeling 

coupled with techniques used to evaluate residential uses of pesticides was utilized. Essentially, a 

residential turf assessment based on exposure to deposited residues has been completed to 

address drift from the agricultural applications of profenofos. In the spray drift scenario, the 

deposited residue value was determined based on the amount of spray drift that may occur at 

varying distances from the edge of the treated field using the AgDrift (v2.1.1) model and the 

Residential Exposure Assessment Standard Operating Procedures Addenda 1: Consideration of 

Spray Drift Policy. Once the deposited residue values were determined, the remainder of the 

spray drift assessment was based on the algorithms and input values specified in the recently 

revised (2012) Standard Operating Procedures For Residential Risk Assessment (SOPs). 

 

8 This approach is consistent with the requirements of the EPA’s Worker Protection Standard.
Page 13 of 35

For profenofos, chemical-specific turf transferable residue (TTR) data are not available, 

therefore, the estimated TTR are based on a default assumption from the 2012 Residential SOPs 

that the transferable residue available for exposure is 1% of the total deposited residue, which is 

assumed to be equivalent to the maximum application rate. 

A screening approach was developed based on the use of the AgDrift model in situations where 

specific label guidance that defines application parameters is not available.9 AgDrift is 

appropriate for use only when applications are made by aircraft, airblast orchard sprayers, and 

groundboom sprayers. When AgDrift was developed, a series of screening values (i.e., the Tier 

1 option) were incorporated into the model and represent each equipment type and use under 

varied conditions. The screening options specifically recommended in this methodology were 

selected because they are plausible and represent a reasonable upper bound level of drift for 

common application methods in agriculture. These screening options are consistent with how 

spray drift is considered in a number of ecological risk assessments and in the process used to 

develop drinking water concentrations used for risk assessment. In all cases, each scenario is to 

be evaluated unless it is not plausible based on the anticipated use pattern (e.g., herbicides are 

not typically applied to tree canopies) or specific label prohibitions (e.g., aerial applications are 

not allowed). Table 5.1.1 provides the screening level drift related risk estimates. 

In many cases, risk estimates are of concern when the screening level estimates for spray drift 

are used as the basis for the analysis. In order to account for this issue and to provide additional 

risk management options, additional spray drift deposition fractions were also considered. These 

drift estimates represent plausible options for pesticide labels.

Combined Risk Estimates from Lawn Deposition Adjacent to Applications

The spray drift risk estimates are based on an estimated deposited residue concentration as a 

result of the screening level agricultural application scenarios. Profenofos is registered on 

cotton, and can only be applied via enclosed cab groundboom equipment at a rate of 0.5 lb ai/A.

The recommended drift scenario screening level options are listed below: 

 Groundboom applications are based on the AgDrift option for high boom height and 

using very fine to fine spray type using the 90th percentile results. 

In addition to the screening level spray drift scenarios described above, additional results are 

provided which represent viable drift reduction technologies (DRTs) that represent potential risk 

management options. In particular, different spray qualities have been considered as well as the 

impact of other application conditions (e.g., boom height and crop canopy conditions).

Dermal risk estimates were calculated for adults. Dermal and incidental oral risk estimates for 

children (1 to <2 years old) were combined because the toxicity endpoint for each route of 

exposure is the same (RBC AChE inhibition). The total applicable LOC is 1000, so MOEs < 

1000 represent risk estimates of concern. 

Risk estimates related to spray drift are of concern at various distances from the edge of the field 

for adults and children (1 to <2 years) depending on the spray drift scenario. Adult and children 

 

9 http://www.agdrift.com/ 
Page 14 of 35

risk estimates are summarized in Table 5.1.1. For adults, the screening level scenario of a high 

boom and very fine to fine spray requires a distance of over 300 feet to reach a dermal MOE ≥ 

1000. For children, the screening level scenario also requires a distance of over 300 feet to reach 

a combined (dermal and incidental oral) MOE ≥1000. Drift reduction technologies, such as 

using coarser sprays and lowering boom height for groundboom sprayers, reduces risk concerns; 

however there are still risk estimates of concern at the field edge. Chemical-specific TTR data 

could be submitted to help refine the spray drift assessment.
Page 15 of 35

Table 6.0.1. Spray Drift Risk Estimate Summary for Profenofos.

Crop / 

Application 

Type

Spray Type/ 

Nozzle 

Configuration

Application 

Rate 

(lb ai/A)

Estimated 

TTRt 

(ug/cm2)

MOE at Different Distances from Edge of Field

(Dermal MOE for Adults;

Dermal + Incidental Oral MOE for Children 1 to <2 years)

LOC = 1000

At 

Edge 10 Feet 25 Feet 50 Feet 75 Feet 100 Feet 125 feet 150 feet 200 feet 250 feet 300 feet

Children (1 to <2 years)

Cotton / 

Groundboom

Screening Level

High Boom Very 

fine to Fine

0.5 0.056

12 25 41 66 92 110 140 160 210 290 330

Low Boom Very 

fine to Fine 27 72 110 180 230 290 330 380 460 570 770

High Boom Fine 

to Medium /

Coarse

47 120 180 260 330 380 460 460 570 770 770

Low Boom Fine 

to Medium /

Coarse

70 190 290 380 460 570 770 770 1,100 1,100 1,100

Adults

Cotton / 

Groundboom

Screening Level

High Boom Very 

fine to Fine

0.5 0.056

25 49 82 130 180 230 270 330 420 570 660 

Low Boom Very 

fine to Fine 54 140 230 350 460 570 660 770 920 1,100 1,500 

High Boom Fine 

to 

Medium/Coarse

94 240 350 510 660 770 920 920 1,100 1,500 1,500 

Low Boom Fine 

to 

Medium/Coarse

 140 380 570 770 920 1,100 1,500 1,500 2,300 2,300 2,300 
Page 16 of 35

7.0 Non-Occupational Bystander Post-Application Inhalation Exposure and Risk 

Estimates

Volatilization of pesticides may be a source of post-application inhalation exposure to 

individuals 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 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) or further 

analysis are required for profenofos.

8.0 Occupational Exposure and Risk Estimates

8.1 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. 

The quantitative exposure/risk assessment developed for occupational handlers is based on the 

following scenarios which cover all the registered use of profenofos: 

 Mixing/loading liquids using closed loading systems to support groundboom 

applications, and

 Applying sprays with closed cab groundboom equipment.

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: The application rate used in this assessment is provided in Section 4.0 (Table 

4.1). 

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, 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 
Page 17 of 35

“Occupational Pesticide Handler Unit Exposure Surrogate Reference Table10”, 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 website11. 

Syngenta had previously submitted a biomonitoring study which examined the potential 

exposure of mixers/loaders and applicators handling profenofos during aerial applications12. 

This study was reviewed by EPA and found to be unacceptable for risk assessment purposes. A 

summary of the study and the reasons why it was not used in risk assessment is provided in 

Appendix B.

Area Treated or Amount Handled: The inputs for area treated were based on information in 

ExpoSAC Policy 9.1, as well as information provided on the label. The label indicates that the 

product is sold in a container containing no more than 10 gallons of the product. In addition, the 

label includes a restriction that mixers/loaders are not allowed to handle more than 10 gallons of 

product per day. Since the product contains 8 lb ai/gal, this equates to a total of 80 lb ai that can 

be handled per day. Policy 9.1 recommends 200 acres for high acreage crops like cotton, which 

with an application rate of 0.5 lb ai/A, equates to 100 lb ai handled per day. Estimates of 

exposure using our default Policy 9.1 assumptions have been presented, as well as those 

assuming only 10 gallons of product are handled per day. The following summarizes the inputs 

used for estimating handler exposures: 

 200 acres for ground application to high acreage crops (from Policy 9.1), and 

 160 acres for ground application (based on label restriction of 80 lb ai handled per day; 

80 lb ai/day ÷ 0.5 lb ai/A = 160 acres)

 

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 

profenofos given the toxicological and exposure profile. The “steady state” endpoint selection 

for profenofos 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). The available 

product label for profenofos indicates that the product can be applied up to 10 times per season 

given the maximum single rate and the maximum seasonal rate.

 

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

11 Available: http://www.epa.gov/pesticides/science/handler-exposure-data.html

12 “Determination of Exposure during the Mixing, Loading, and Application of Curacron 8E (Profenofos) by Air through the Use 

of Biological Monitoring” (MRID 46204902; D363390; 26-MAR-2009)
Page 18 of 35

Mitigation/Personal Protective Equipment: The registered profenofos label requires a closed 

mixing/loading system and an enclosed cab. In addition, mixer, loaders, applicators, and other 

handlers using a closed system must also wear long sleeved shirt, long pants, shoes plus socks, 

chemical-resistant gloves, chemical-resistant apron (for mixing and loading), and protective 

eyewear. Estimates of dermal and inhalation exposure were calculated assuming the use of 

engineering controls as required by the label. 

Occupational Handler Non-Cancer Exposure and Risk Estimate Equations

The algorithms used to estimate non-cancer exposure and dose for occupational handlers can be 

found in Appendix A.

Combining Exposures/Risk Estimates

A total ARI was 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 ARI was calculated as follows.

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

Summary of Occupational Handler Non-Cancer Exposure and Risk Estimates

The occupational handler exposure and risk estimates indicate that the dermal and inhalation 

combined MOEs are of concern to HED (i.e., ARI < 1) for all scenarios. ARIs range from 0.08 

to 0.14 using HED defaults for area treated per day, and from 0.1 to 0.17 using an adjusted area 

treated per day to account for a label restriction on the maximum amount of ai that can be 

handled per day. Table 8.1.1 provides a summary of the occupational handler risk estimates. 
Page 19 of 35

Table 8.1.1. Summary of Occupational Handler Risk Estimates for Profenofos.

Exposure 

Scenario

Crop / 

Target 

Category

App 

Rate2

Area 

Treated3

Engineering Control Unit 

Exposure 

(ug/lb ai)

1

Engineering Control Dose 

(mg/kg/day) Engineering Control MOE Engineering 

Control ARI8

Dermal Inhalation Dermal4Inhalation6 Dermal5

(LOC = 1000)

Inhalation7

(LOC = 3000)

Mixing / loading 

liquids for 

groundboom 

application

Cotton 0.5 lb 

ai/A

200 acres

8.6 0.083 0.0125 0.00012 80 85,000 0.08

Applying via 

groundboom 5.1 0.043 0.00739 0.0000623 140 160,000 0.14

Mixing / loading 

liquids for 

groundboom 

application 160 acres

8.6 0.083 0.00997 0.0000962 100 110,000 0.1

Applying via 

groundboom 5.1 0.043 0.00591 0.0000499 170 200,000 0.17

1 Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (March 2013]); Level of mitigation: Eng. Controls.

2 Based on registered label (Reg. No. 100-669).

3 Exposure Science Advisory Council Policy #9.1 and information provided on labels regarding maximum amount of product that can be handled by mixers/loaders per day (10 gallons).

4 Dermal Dose = Dermal Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre) × Area Treated (A/day) ÷ BW (69 kg).

5 Dermal MOE = Dermal POD (1 mg/kg/day) ÷ Dermal Dose (mg/kg/day).

6 Inhalation Dose = Inhalation Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre) × Area Treated (A/day) ÷ BW (69 kg).

7 Inhalation MOE = Inhalation POD (mg/kg/day) ÷ Inhalation Dose (mg/kg/day). Inhalation PODs (2.90, 5.84, and 10.14 mg/kg/day) related to breathing rates (8.3, 16.7, or 29 L/min).

8 ARI = Aggregate Risk Index = 1÷ [(Dermal LOC ÷ Dermal MOE) + (Inhalation LOC ÷ Inhalation MOE)].
Page 20 of 35

8.2 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.

8.2.1 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) or further analysis is required for profenofos.

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.

8.2.2 Occupational Post-application Dermal Exposure/Risk Estimates

Occupational Post-application Dermal Exposure Data and Assumptions

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

post-application risk assessments. Each assumption and factor is detailed below on an individual 

basis. 

Exposure Duration: 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 profenofos given the toxicological and exposure 

profile. The “steady state” endpoint selection for profenofos overlaps HED’s traditional shortterm exposure duration endpoint selection as well as being appropriately health protective for 

workers that are exposed over longer periods of time (i.e., intermediate-term exposures).
Page 21 of 35

Transfer Coefficients: It is the policy of HED to use the best available data to assess postapplication exposure. Sources of generic post-application data, used as surrogate data in the 

absence of chemical-specific data, are derived from ARTF exposure monitoring studies, and, as 

proprietary data, are subject to the data protection provisions of FIFRA. The standard values 

recommended for use in predicting post-application exposure that are used in this assessment, 

known as “transfer coefficients”, are presented in the ExpoSAC Policy 313” which, along with 

additional information about the ARTF data, can be found at the Agency website14. 

It is noted that the Registrant had previously submitted a worker reentry exposure study from 

which chemical-specific transfer coefficients were calculated. This study was reviewed and 

found acceptable for risk assessment15. However, this study has not been used as an independent 

chemical-specific study since it has been incorporated into EPA’s Science Advisory Council for 

Exposure (ExpoSAC) Policy 3 (http://www.epa.gov/pesticides/science/exposac-policy-3-

march2013.pdf). The recommended transfer coefficients from this policy are recommended for 

use in the profenofos risk assessment, and these are provided in Table 8.2.2.1 below.

Table 8.2.2.1. Anticipated Post-Application Activities and Dermal Transfer Coefficients.

Crop Policy Crop 

Group Category

Crop 

Height

Foliage 

Density Transfer Coefficients Activities

Cotton Field / row crop, 

low / medium

Low Min/Full

70 cm2/hr Hand weeding

210 cm2/hr Scouting

High Min

900 gm cotton boll/hr Mechanical Harvesting (Module 

Builder Operator)

2400 gm cotton boll/hr Mechanical Harvesting 

(Picker Operator and Raker)

5050 gm cotton boll/hr Mechanical Harvesting (Tramper)

Application Rate: The application rate used in this assessment is provided in Section 4.0 (Table 

4.1). 

Exposure Time: The average occupational workday is assumed to be 8 hours. 

Chemical-specific Residue Data: 

DFR: Chemical-specific DFR data have been submitted for profenofos. Three studies 

were submitted that examined residues of profenofos on cotton foliage in various 

locations: California (MRID 4281303), Texas (MRID 4281303), and North and South 

Carolina (MRID 4281302). All three studies have been reviewed by HED and found to 

be acceptable for risk assessment. All of the cotton foliage data represent DFR levels 

obtained at an application rate of 1.0 lb ai/A. The DFR residues (μg/cm2) were adjusted 

 

13 Available: http://www.epa.gov/pesticides/science/exposac_policy3.pdf

14 Available: http://www.epa.gov/pesticides/science/post-app-exposure-data.html

15

“Worker Reentry Exposure to Profenofos in Cotton Treated with Curacron® 8E” (D429108; MRID 4281302; 15-SEP-2015).
Page 22 of 35

to account for the difference in application rate for the registered crop (cotton @ 0.5 lb 

ai/A). For more information on the study and results, see Appendix B.

Cotton bolls: 

One of the studies (MRID 4281302) also collected dislodgeable residue data on cotton 

bolls. Cotton boll samples were collected at 44 – 70 days after treatment (DAT), and 

were less the level of quantification (LOQ, 0.75 ug). Each sample consisted of 5 cotton 

bolls, and weighed a total of 1.44 g per sample, resulting in a residue value of 0.52 ug/g 

at the LOQ. One-half the LOQ was used in calculating dislodgeable residue, which 

resulted in a residue value of 0.26 ug/g on Day 44 after application. 

Since profenofos has a pre-harvest interval (PHI) of 14 days, it would be possible for 

harvesting activities to occur on DAT 14; therefore, a back-calculation was performed to 

estimate a residue value on Day 14 (assuming there had been 10% dissipation per day

which is HED’s default dissipation assumption for post-application assessments). This 

calculated value (4.54 ug ai/g cotton) was used in calculating post-application exposure 

resulting from application of profenofos to cotton during harvesting activities (e.g., 

module builder, picker operator, raker, tramper). 

Occupational Post-application Non-Cancer Dermal Exposure and Risk Estimate Equations

The algorithms used to estimate non-cancer exposure and dose for occupational post-application 

workers can be found in Appendix A.

Occupational Post-application Non-Cancer Dermal Risk Estimates

Tables 8.2.2.2 and 8.2.2.3 provide summaries of the exposure and risk estimates for postapplication activities associated with cotton. Even though the profenofos label requires 

mechanically harvesting, there are post-application activities associated with mechanical 

harvesting that can result in potential exposure. These activities have been assessed using the 

available cotton boll residue data. 

Based on the current exposure assessment, post-application risk estimates remain a concern (i.e., 

MOEs < 1000) up to 4 days after application for hand weeding and up to 9 days after application

for scouting. Post-application risk estimates associated with harvesting activities are a concern 

(MOEs < 1000) 14 days after treatment, which would be the earliest harvesting could occur after 

application based on the current pre-harvest interval (PHI). An additional calculation was 

performed to estimate post-application exposure and risk using the cotton boll residue data from 

the day of sampling (day 44); however, there were still risk estimates of concern for all 

harvesting activities even 44 days after application at which point residue values were less than 

the LOQ in the study. 

Table 8.2.2.2. Occupational Post-application Non-Cancer Exposure and Risk Estimates for Profenofos on Cotton.

Activities

Transfer 

Coefficient 

(cm2/hr)

Site Days after 

application DFR/TTR1 Dermal Dose(mg/kg/day)2

MOE3

(LOC = 1000)

Hand weeding 70 CA

0 (12 hours) 1.72 0.0121 83

1 0.45 0.0031 320
Page 23 of 35

Table 8.2.2.2. Occupational Post-application Non-Cancer Exposure and Risk Estimates for Profenofos on Cotton.

Activities

Transfer 

Coefficient 

(cm2/hr)

Site Days after 

application DFR/TTR1 Dermal Dose(mg/kg/day)2

MOE3

(LOC = 1000)

2 0.22 0.0015 650

3 0.17 0.0012 830

4 0.13 0.0009 1,100

TX

0 (12 hours) 2.44 0.020 51

1 0.33 0.003 380

2 0.11 0.001 1,200

Cheraw, SC

0 (12 hours) 2.25 0.018 55

1 0.46 0.0037 270

2 0.094 0.00076 1,300

Chesterfield, SC

0 (12 hours) 2.99 0.024 41

1 1.20 0.0098 100

2 0.483 0.0039 260

3 0.194 0.0016 640

4 0.078 0.00063 1,600

NC

0 (12 hours) 2.69 0.022 46

1 0.26 0.0021 480

2 0.02 0.00020 5,000

Scouting 210

CA

0 (12 hours) 1.72 0.0362 28

1 0.45 0.0094 110

2 0.220 0.0046 220

3 0.171 0.0036 280

4 0.133 0.0028 360

5 0.104 0.0022 460

6 0.081 0.0017 590

7 0.063 0.0013 760

8 0.049 0.0010 970

9 0.038 0.0008 1,300

TX

0 (12 hours) 2.44 0.059 17

1 0.33 0.008 130

2 0.11 0.003 390

3 0.08 0.002 510

4 0.06 0.001 670

5 0.05 0.001 880

6 0.04 0.059 1,200

Cheraw, SC

0 (12 hours) 2.25 0.055 18

1 0.46 0.011 89

2 0.094 0.0023 440

3 0.019 0.00047 2,100

Chesterfield, SC 0 (12 hours) 2.99 0.073 14
Page 24 of 35

Table 8.2.2.2. Occupational Post-application Non-Cancer Exposure and Risk Estimates for Profenofos on Cotton.

Activities

Transfer 

Coefficient 

(cm2/hr)

Site Days after 

application DFR/TTR1 Dermal Dose(mg/kg/day)2

MOE3

(LOC = 1000)

1 1.20 0.029 34

2 0.483 0.012 85

3 0.194 0.0047 210

4 0.078 0.0019 530

5 2.99 0.00076 1,300

NC

0 (12 hours) 2.69 0.066 15

1 0.26 0.0063 160

2 0.02 0.00060 1,700

1 DFR = Predicted profenofos residues (based on a biphasic regression analysis) adjusted to account for application rate differences. See 

Appendix C for more information on DFR study and regression analysis.

2 Daily Dermal Dose = [DFR (μg/cm2) × Transfer Coefficient × 0.001 mg/μg × 8 hrs/day]  BW (69 kg).

3 MOE = POD (1 mg/kg/day) / Daily Dermal Dose. 

Table 8.2.2.3. Post-Application Exposure and Risk Estimates for use of Profenofos on Cotton during Harvesting 

Activities.

Crop

Proposed 

Maximum 

Seasonal 

Application 

Rate

(lb ai/A)

Activity TC1

(g cotton/hr)

Days After 

Treatment

Cotton boll 

residue2

(ug ai/g 

cotton)

Daily Dose 

(mg/kg/day)

3

MOE4

(LOC = 

1000)

Cotton 0.5

Harvesting 

Mechanical 

(Module Builder)

900

14

(pre-harvest

interval)

4.54

0.474 2.1

Harvesting 

Mechanical 

(Picker Operator; 

Raker)

2400 1.264 0.79

Harvesting 

Mechanical 

(Tramper)

5050 2.661 0.38

Harvesting 

Mechanical 

(Module Builder)

900

44

(sampling 

day)

0.26

0.027 37

Harvesting 

Mechanical 

(Picker Operator; 

Raker)

2400 0.072 14

Harvesting 

Mechanical 

(Tramper)

5050 0.152 6.6

1. Transfer Coefficients from HED Policy No. 3.0., Non-Foliar Transfer Coefficient Table, March 2012 (p 122). 

2. Residue value from MRID 4281302. On sampling day 44, residues reported as <LOQ (75 ug) and cotton boll sample weighed 

1.44 g; therefore, residues = 0.52 ug/g. Per HED policy, 1⁄2 LOQ value used in calculations (0.26 ug/g). Day 14 (the pre-harvest 

interval) residues were back-calculated assuming 10% dissipation had occurred per day from day 14 to day 44.

3. Dermal Dose (mg/kg/day) = [Cotton Boll residue, ug ai/g cotton) x TC (g cotton/hr) x hr/day (8 hrs/day)] / BW (69 kg).

4. Dermal MOE = NOAEL (1 mg/kg/day)/Dermal Dose (mg/kg/day); LOC = 1000.

Restricted Entry Interval (REI)
Page 25 of 35

The current product-label REI is 48 hours (72 hours in areas where rainfall is less than 25 inches 

per year). Under 40 CFR 156.208 (c) (2) (i), ai’s classified as Acute toxicity category I for acute 

dermal, eye irritation or primary skin irritation are assigned a 48-hour REI. In addition, for 

organophosphates that may be applied outdoors in an area where the average annual rainfall for 

the site is less than 25 inches per year, the REI shall be 72 hours. However, based on the current 

post-application dermal exposure assessment, a REI of at least 9 days is necessary for scouting, 

and a REI of 4 days is necessary for hand weeding. In addition, activities associated with 

harvesting of cotton are of concern at the current PHI. Increasing the PHI is unlikely to impact 

the risk estimates since MOEs for activities associated with mechanical harvesting using the Day 

44 residue value from the submitted study are still less than the LOC.

 
Page 26 of 35

Appendix A. Summary of Occupational and Residential Non-cancer Algorithms

OCCUPATIONAL NON-CANCER HANDLER ALGORITHMS

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

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

where:

E = exposure (mg ai/day),

UE = unit exposure (μg ai/lb ai),

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

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

The daily doses are calculated using the following formula:

ADD= 

E * AF

BW

where:

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

E = exposure (mg ai/day),

AF = absorption factor (dermal and/or inhalation), and

BW = body weight (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 are compared to the appropriate POD to assess the risk to occupational handlers for 

each exposure route. All MOE values are calculated using the following formula:

MOE= 

POD

ADD

where:

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

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

ADD = average daily dose absorbed in a given scenario (mg ai/kg/day).
Page 27 of 35

OCCUPATIONAL NON-CANCER POST-APPLICATION ALGORITHMS

Potential daily exposures for occupational post-application workers are calculated using the 

following formulas. DFR from chemical-specific studies were used in the post-application 

calculations. 

Post-application exposure was calculated using the following formula:

E=TC * DFR t * ET * 0.001

mg

ug

where:

E = exposure (mg ai/day),

TC = transfer coefficient (cm2/hr),

DFRt = dislodgeable foliar residue on day “t” (μg/cm2), and

ET = exposure time (hours/day).

The daily doses are calculated using the following formula:

ADD= 

E * AF

BW

where:

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

E = exposure (mg ai/day),

AF = absorption factor (dermal and/or inhalation), and

BW = body weight (kg).

Margin of Exposure: Non-cancer risk estimates for each scenario are calculated using a Margin 

of Exposure (MOE), which is a ratio of the toxicological endpoint to the daily dose of concern. 

The daily dermal dose received by occupational post-application workers is compared to the 

appropriate POD to assess the risk to occupational post-application workers. All MOE values 

are calculated using the following formula:

MOE= 

POD

ADD

where:

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

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

ADD = average daily dose absorbed in a given scenario (mg ai/kg/day).
Page 28 of 35

Appendix B. Summary of Biomonitoring Study Available for Profenofos

Syngenta submitted a biomonitoring study (Determination of Exposure during the Mixing, 

Loading, and Application of Curacron 8E (Profenofos) by Air through the Use of Biological 

Monitoring (MRID 46204902) which examined the potential profenofos exposure to 

mixers/loaders and applicators handling the pesticide product Curacron 8E. This study was 

initially reviewed by HED in February of 2007 and HED requested additional information 

related to several questions identified during the review (D301892). In a 2008 document, HED 

commented on the responses received by Syngenta, and noted issues that were still unresolved 

(D349260). In 2009, HED provided a final review of the biomonitoring study, noting the 

unresolved issues and reasons for finding the study unacceptable for use in risk assessment 

(D363390). A summary of the study, as well as the conclusions reached by HED, is provided 

below. 

The biomonitoring study was designed to examine the absorbed dose of handlers using a closed 

mixing/loading system and aerial application (enclosed cockpit fixed-wing aircraft) of 

profenofos. Sixteen mixing/loading replicates and sixteen applicator replicates were monitored 

in Texas, Mississippi, and Louisiana. The test substance was packaged in 2.5 gallon jugs that 

were specially designed to work with the Securalink-G closed transfer handling system. The 

pilots treated approximately 400 to 480 acres of cotton at an application rate of 1 lb ai/A, which 

involved the mixer/loaders handling between 50 and 60 gallons of test product (2 spray cycles). 

Twelve-hour composite urine samples were collected from each handler starting from 24-hours 

prior to the time of monitoring through 72 hours after application. In the analysis phase of the 

study, profenofos and all urinary metabolites were converted to 4-bromo-2-chlorophenol (4,2-

BCP) for quantitation. According to the study author, the predominate form of metabolized 

profenofos in urine is the glucoronic acid conjugate of 4,2-BCP (CGA-55163). The study author 

converted the 4,2-BCP residues detected in the samples to proposed profenofos equivalent 

absorbed doses.

The concerns that HED had regarding the study included the following:

1) A concern was identified over different closed systems used between the study and those 

currently used. The test product was packaged in 2.5 gallon containers with a 

permanently installed special valve mounted in the container opening. The special 

adaptor caps were designed for a closed transfer handling system called Securalink-G. 

The study author states that since this study was conducted, Syngenta has discontinued 

selling the 2.5 gallon containers and only sells Curacron in 15-gallon mini-bulk 

containers with the Micro MaticTM closed mixing/loading system. Syngenta has not 

submitted data indicating how exposures resulting from the use of a Micro MaticTM 

packaging system relate to exposures resulting from the use of the SecuraLink-G 

packaging. Therefore, there are no data indicating that exposure data from the 

SecuraLink-G biomonitoring study would be appropriate as surrogate data for exposures 

resulting from the use of a Micro MaticTM packaging system.
Page 29 of 35

2) There was concern over whether 72 hours was sufficiently long enough to recover 

urinary metabolites given the high percentages of profenofos spikes in urine in the 36- to 

72-hour collection periods, and the relatively significant levels of profenofos equivalents 

recovered up to and including the 60- to 72-hour collection period. In 12 out of 14 (86%) 

of the mixer/loader replicates and in 10 out of 14 (71%) of the applicator replicates, urine 

samples indicate an increase in profenofos during the second 36 hours of collection. 

3) The monkey pharmacokinetic study involved 5 monkeys and included concerns about 

incomplete urine collection in the first collection period. The study was classified as 

acceptable/nonguideline by EPA. HED is concerned that the pharmacokinetic study may 

not have adequately measured the profenofos metabolites excreted in monkey urine and 

questions using that study as the pharmacokinetic basis for the human biomonitoring 

study. 

4) HED raised a question regarding the adjustment factor for absorbed profenofos. HED 

noted that it was necessary to use an adjustment factor in the absorbed dose calculation to 

estimate the amount of profenofos and all metabolites that are eliminated in urine in the 

first 72-hours following a single oral dose (from the monkey pharmacokinetic study).

5) HED questioned whether an additional adjustment factor was necessary to estimate 

absorbed profenofos from the measured absorbed metabolite. Since the pharmacokinetic 

study reports that an average of 74% of the metabolites excreted in urine was CGA55163, HED believes that profenofos equivalents should be adjusted to reflect that only 

74% of the profenofos equivalents are CGA-55163.

6) HED questioned whether an additional adjustment factor was necessary to account for the 

percent of one of the metabolites that was not converted to 4,2-BCP and not detected as 

potential exposure to profenofos. In the pharmacokinetic study, 12.7% of CGA-55163 

was not converted to 4,2-BCP. Therefore, it is of potential concern that not all of the 

CGA-55163 was detected and quantified in the biomonitoring study. However, as 

laboratory and field fortification samples were prepared in the biological monitoring 

study it can be assumed that corrections for these recoveries will account for the 

conversion of CGA-55163 to 4,2-BCP. Because the field fortification samples in this 

study were not run concurrently with the actual sample analysis (they were analyzed

approximately one year after the study was completed), the laboratory fortification 

recoveries were assessed. Average laboratory recoveries were greater than 90% in the 

biomonitoring study; therefore, an additional correction for laboratory recovery was not 

used.

7) HED had concerns over the representativeness of 400-480 acres treated for handlers per 

day for cotton, and whether handling such relatively small quantities of profenofos for 

relatively short periods of time can be accurately extrapolated to reflect potential 

exposure for a full 8-hour workday.

8) HED had concerns about whether the study represented a full day of work for the 
Page 30 of 35

handlers. During the study, the mixer/loaders handled profenofos an average of only 1 

hour and 17 minutes and the pilots applied profenofos an average of only 1 hour and 29 

minutes. 

9) HED had concerns that the field recovery samples were conducted 1 year after the 

conduct of the study and cannot adequately fulfill the intent of field recovery sampling.

10) Profenofos residues were detected in pre-exposure samples in approximately one–half of 

handlers (15 of the 32 handlers). Each handler claimed not to have used or handled 

Curacron for the week prior to the study. It is possible that the handlers received 

exposure to the chemical but did not report it.
Page 31 of 35

Appendix C. Summary of Available DFR Data for Profenofos

“Dissipation of Dislodgeable Foliar Residues of Profenofos (Curacron ® 8E) Applied to Cotton in 

California” MRID 42851303

This study was designed to determine the dissipation of dislodgeable foliar residues (DFRs) of the active 

ingredient (ai) profenofos from treated cotton foliage. The test product was a 73% ai emulsifiable 

concentrate (EC) formulation. One test site was examined in Madera, CA (NAFTA Region 10) during 

the 1991 growing season. Geographical and climatic conditions were relevant to the use pattern 

proposed. The trial site consisted of one control plot and one treatment plot, with the treatment plot 

receiving six foliar broadcast spray applications of the test substance via tractor-mounted groundboom 

sprayers at a nominal rate of 1.0 lb ai/A/application. Applications were made using a spray volume of 

approximately 30 gallons per acre, at retreatment intervals of 5-6 days.

Single control plot and triplicate treated plot DFR samples were collected using a Birkestrand leaf punch 

sampler prior to and after the first, third, and sixth (last) application, and at the following intervals after 

the last application: 1, 2, 3, 7, 14, 21, 28, and 35 days. EPA calculated DFRs in μg/cm2, correcting for 

field fortification recoveries and a leaf surface area of 400 cm2. 

The highest average DFR was 1.66 μg/cm2, which occurred immediately after the first application 

(14.8% of application rate). The average DFR immediately prior to the last (sixth) application was 0.120 

μg/cm2. The maximum average DFR after the last application occurred at the first sampling interval 

(after spray dried) with a value of 1.38 μg/cm2 (12.3% of application rate). DFRs declined rapidly in the 

first three days to 0.162 μg/cm2 (1.4% of application rate) at 3DAT6, and reached equilibrium at 

21DAT6 with a value of 0.010 μg/cm2 (0.09% of application rate). DFRs on 28DAT6 and 35DAT6 were 

0.011 and 0.0081 μg/cm2, respectively.

 

The Registrant assumed first-order dissipation kinetics to generate dissipation curves for profenofos. The 

Registrant conducted linear regression analyses using the natural logarithm of average DFR values from 

the following sampling intervals: 1) 0DAT6 through 35DAT6 (all sampling intervals after the last 

application), 2) 0DAT6 though 21DAT6 (sampling intervals through the point of equilibrium), 3) 0DAT6 

through 3DAT6 (first part of bi-phasic pattern), and 4) 3DAT6 through 35DAT6 (second part of bi-phasic 

pattern). The Registrant’s calculated half-lives for these intervals, respectively, were 5.4 days (R2 = 

0.816), 3.4 days (R2 = 0.881), 1.0 days (R2 = 0.942), and 7.9 days (R2 = 0.848). Additionally, the 

Registrant generated a decline curve fit using an equation representing the data specifically (y=a+bexp-x), 

as determined by Table Curve Fitting Software. The half-life calculated was 0.7 days (R2 = 0.993).

EPA first assumed first-order dissipation kinetics and conducted a linear regression analysis using the 

corrected average DFRs from immediately after the last application (0DAT6) through the last sampling 

interval (35DAT6), and determined a half-life of 5.4 days (R2 = 0.8212). However, the regression 

analysis did not appear visually to be a good fit for the data, and a comparison of the 0DAT6 actual and 

predicted DFRs show that the actual DFR (1.38 μg/cm2) is ~4x higher than the linear regression predicted 

DFR (0.3357 μg/cm2). Therefore, EPA did additional analysis and conducted a biphasic regression 

analysis using Excel’s Solver, and the corrected average DFRs from immediately after the last application 

through the last sampling interval. This regression analysis appears (visually) to be a better fit of the data, 

and provides a predicted Day 0 value of 1.74 μg/cm2. 

No major issues were identified during review of this study and the results are considered acceptable for 

risk assessment purposes. There were some issues noted regarding the field fortification recovery 
Page 32 of 35

samples: (1) only one field fortification level was used in the study, and the EPA guideline recommends a 

minimum of two field fortification levels; (2) the level chosen was below most of the field samples (10 

ug/sample for the field fortification samples vs a maximum of 648 ug/sample for the field samples); and 

(3) several recoveries were outside the guideline range of 70-120%. However, the study report did 

provide additional information with respect to laboratory recovery samples, which included 

concentrations up to 1000 ug/sample, with recoveries ranging from 88 – 121%; therefore, it is unlikely 

that the field fortification issues would impact the utility of the study for risk assessment.

Summary of DFR Values and EPA Regression Analysis Results for Treated Cotton with Profenofos 

(MRID# 42851303).

Cotton; Site: Madera, CA

Study Target Rate (lb ai/A) 1.00 lb ai/A

Spray Volume (GPA) 30

Measured Average Day 0 Residue (μg/cm2) 0DAT6: 1.38

Linear Regression Predicted Day 0 Residue (μg/cm2) 0DAT6: 0.336

Slope -0.129

Half-life (days) 5.4

R

2 0.8212

Biphasic Regression Predicted Day 0 Residue (ug/cm2) 0DAT6: 1.74

Slope -1.345, -0.251

Inflection Point (day) 1

“Dissipation of Dislodgeable Foliar Residues of Profenofos (Curacron® 8E) Applied to Cotton in 

Texas” MRID 42851304

This study was designed to determine the dissipation of dislodgeable foliar residues (DFRs) of the active 

ingredient (ai) profenofos from treated cotton foliage. The test product was a 73% ai emulsifiable 

concentrate (EC) formulation. One test site was examined in Snook, Texas (NAFTA Region 6) during 

the 1991 growing season. Geographical and climatic conditions were relevant to the use pattern 

proposed. The trial site consisted of one control plot and one treatment plot, with the treatment plot 

receiving six foliar broadcast spray applications of the test substance via tractor-mounted groundboom 

sprayers at a nominal rate of 1.0 lb ai/A/application. Applications were made using a spray volume 

between 19.4-21.5 gallons per acre, at retreatment intervals of 5-7 days.

Single control plot and triplicate treated plot DFR samples were collected using a Birkestrand leaf punch 

sampler prior to and after the first, third, and sixth (last) application, and at the following intervals after 

the last application: 1, 2, 3, 7, 14, 21, 28, and 35 days. EPA calculated DFRs in μg/cm2 using the same 

field fortification correction factor, and used a leaf surface area of 400 cm2. 

The highest average DFR was 2.11 μg/cm2, which occurred immediately after the first application 

(20.4% of application rate). The average DFR immediately prior to the last (sixth) application was 0.054 

μg/cm2. The maximum average DFR after the last application occurred at the first sampling interval 

(after spray dried) with a value of 1.74 μg/cm2 (16.0% of application rate). DFRs declined rapidly in the 

first three days to 0.076 μg/cm2 (0.7% of application rate) at 3DAT6, and reached equilibrium at 
Page 33 of 35

21DAT6 with a value of 0.0086 μg/cm2 (0.08% of application rate). DFRs on 28DAT6 and 35DAT6 

were 0.0066 and 0.0086 μg/cm2, respectively.

 

The Registrant assumed first-order dissipation kinetics to generate dissipation curves for profenofos. The 

Registrant conducted linear regression analyses using the natural logarithm of average DFR values from 

the following sampling intervals: 1) 0DAT6 through 35DAT6 (all sampling intervals after the last 

application), 2) 0DAT6 though 21DAT6 (sampling intervals through the point of equilibrium), 3) 0DAT6 

through 3DAT6 (first part of bi-phasic pattern), and 4) 3DAT6 through 35DAT6 (second part of bi-phasic 

pattern). The Registrant’s calculated half-lives for these intervals, respectively, were 5.7 days (R2 = 

0.659), 3.4 days (R2 = 0.723), 16 hours (R2 = 0.924), and 10.8 days (R2 = 0.731). 

EPA first assumed first-order dissipation kinetics and conducted a linear regression analysis using the 

corrected average DFRs from immediately after the last application (0DAT6) through the last sampling 

interval (35DAT6), and determined a half-life of 5.7 days (R2 = 0.6694). However, the regression 

analysis did not appear visually to be a good fit for the data, and a comparison of the 0DAT6 actual and 

predicted DFRs show that the actual DFR (1.74 μg/cm2) is ~4x higher than the linear regression predicted 

DFR (0.2005 μg/cm2). Therefore, EPA did additional analysis and conducted a biphasic regression 

analysis using Excel’s Solver, and the corrected average DFRs from immediately after the last application 

through the last sampling interval. This regression analysis appears (visually) to be a better fit of the data, 

and provides a predicted Day 0 value of 2.4 μg/cm2.

There were some issues noted regarding the field fortification recovery samples: (1) only one field 

fortification level as used in the study, and the EPA guideline recommends a minimum of two field 

fortification levels; (2) the level chosen was below most of the field samples (10 ug/sample for the field 

fortification samples vs a maximum of 648 ug/sample for the field samples); and (3) several recoveries 

were outside the guideline range of 70-120%. However, the study report did provide additional 

information with respect to laboratory recovery samples, which included concentrations up to 1000 

ug/sample, with recoveries ranging from 88 – 121%.

Summary of DFR Values and EPA Regression Analysis Results for Treated Cotton with Profenofos 

(MRID# 42851303).

Cotton; Site: Snook, TX

Study Target Rate (lb ai/A) 1.00 lb ai/A

Spray Volume (GPA) 19.4-21.5

Measured Average Day 0 Residue (μg/cm2) 0DAT6: 1.74

Linear Regression Predicted Day 0 Residue (μg/cm2) 0DAT6: 0.2005

Slope -0.121

Half-life (days) 5.7

R

2 0.6694

Biphasic Regression Predicted Day 0 Residue (ug/cm2) 0DAT6: 2.4

Slope -2.015, -0.272

Inflection Point (day) 1
Page 34 of 35

“Worker Reentry Exposure to Profenofos in Cotton Treated with Curacron® 8E” MRID 42851302

The study was conducted during the 1992 growing season at three test sites located in NAFTA Region 2. 

Test sites 1, 2, and 3 were located in Cheraw, SC, McFarlan, NC, and Chesterfield, SC, respectively. The 

sites were approximately 2 to 8 miles from each other. Geographical and climatic conditions were 

relevant to the use pattern proposed. The trial sites consisted of one control plot and one treatment plot, 

with the treatment plot receiving six foliar broadcast applications of profenofos, formulated as an 

emulsifiable concentrate (EC) containing 73% of the active ingredient (ai) profenofos. Applications were 

made to cotton via tractor-mounted groundboom sprayers at a target rate of 1 lb ai/A/application. The 

applications were made at 5-8 day re-treatment intervals using a spray volume of 15-17 gallons of water 

per acre (GPA).

Duplicate control plot and treated plot DFR samples were collected using a Birkestrand leaf punch 

sampler prior to and after the first application, after the second application, prior to and after the third 

application, after the fourth and fifth applications, prior to and after the sixth (last) application, and at the 

following intervals after the last application: 1, 2, 3, 7, 14, 21, 28 and 35 days. 

EPA calculated DFRs in μg/cm2(based on a 250 cm2leaf surface area) with correction for the average 

low and high field fortification recoveries of each site separately. In general, DFRs at all sites declined 

rapidly within the first week after the last application, and then remained at low levels through the end of 

the sampling period. Residues did not decline to <LOQ (0.003 μg/cm2) by 35DAT6.

The average DFR (and percent of application rate) at the Cheraw, SC, site was the highest at the 0DAT5 

interval (2.83 μg/cm2; 26.5%). After the last application, the average DFR was a maximum of 1.74 

μg/cm2(16.3%) at 0DAT6, declined to 0.40 μg/cm2(3.8%) at 1DAT6, and continued to decline to 0.0047 

μg/cm2(0.04%) at 35DAT6. 

The average DFR (and percent of application rate) at the McFarland, NC, site was the highest at the 

0DAT2 interval (3.99 μg/cm2; 29.7%). After the last application, the average DFR was a maximum of 

1.82 μg/cm2(17.1%) at 0DAT6, declined to 0.251 μg/cm2(2.4%) at 1DAT6, and continued to decline to 

0.0046 μg/cm2(0.04%) at 35DAT6. 

The average DFR (and percent of application rate) at the Chesterfield, SC, site was the highest at the 

0DAT5 interval (5.19 μg/cm2; 44.5%). After the last application, the average DFR was a maximum of 

2.48 μg/cm2(23.3%) at 0DAT6, declined to 1.54 μg/cm2(14.4%) at 1DAT6, and continued to decline to 

0.0056 μg/cm2(0.05%) at 35DAT6. Actual DFRs on 0DAT6 were 7 to 12 times higher than the 

predicted DFRs on 0DAT6.

The Registrant assumed first-order dissipation kinetics to generate dissipation curves for profenofos, 

using the natural log of average DFR values. Using the 0DAT6 to 35DAT6 data, the Registrant 

calculated half-lives of 5 days (r = -0.85) for Site 1, 4.9 days (r = -0.77) for Site 2, and 4.6 days (r = -0.79) 

for Site 3. The Registrant also performed regressions using the 0DAT6 through 7DAT6 data only, which 

assumes a biphasic curve. The Registrant calculated half-lives of 1.2 days (r = -0.91) for Site 1 (Cheraw, 

SC), 1.1 days (r = -0.80) for Site 2 (Chesterfield, SC), and 0.86 days (r = -0.95) for Site 3 (McFarlan, 

NC).

EPA first assumed first-order dissipation kinetics and conducted linear regression analysis using the 

natural logarithm of the average DFR values from 0DAT6 to 35DAT6. EPA's estimated half-life values 

were 5.1 days (R2= 0.7132) for Site 1, 5.7 days (R2= 0.6351) for Site 2, and 4.7 days (R2= 0.6271) for Site 

3. However, the regression analysis did not appear visually to be a good fit for the data, and the actual 
Page 35 of 35

DFRs on 0DAT6 were 7 to 12 times higher than the predicted DFRs on 0DAT6. Therefore, EPA did 

additional analysis and conducted a biphasic regression analysis using Excel’s Solver, and the corrected 

average DFRs from immediately after the last application through the last sampling interval. This 

regression analysis appears (visually) to be a better fit of the data, and provides predicted Day 0 values of 

2.3 μg/cm2, 3.0 μg/cm2, and 2.7 μg/cm2, for Site 1 (Cheraw, SC), Site 2 (Chesterfield, SC), and Site 3 

(McFarlan, NC), respectively.

There were some issues noted with respect to the DFR study. However, these are not anticipated to 

impact the validity of the data or its use in risk assessment. These issues included: (1) only duplicate 

DFR samples were collected at each interval; the guidelines recommend the collection of triplicate DFR 

samples; (2) two field fortification levels were used (200 μg and 20,000 μg), as recommended in the EPA 

guidelines; however, the high fortification level was significantly higher than the treated samples; and (3) 

the EPA guidelines recommend a sample surface are of 400 cm2; however, in this study, the total leaf 

surface was only 250 cm2, as reported in the main text of the study. It should also be noted that the study 

actually used a surface area of 227 cm2to calculate DFRs, based on a punch diameter of 1.7 cm. The 

Rabbit Tool website (the manufacturer of Birkestrand punches) states that the 2.5 cm2 punch has a 

diameter of 1.784 cm2, thus it appears that the surface area of 227 cm2is incorrect.

Summary of DFR Values and EPA Regression Analysis Results for Treated Cotton with Profenofos 

(MRID# 42851302).

Site Cheraw, SC Chesterfield, 

SC

McFarland, 

NC

Study Target Rate (lb ai/A) 1 lb ai/acre

Spray Volume (GPA) 15-17

Measured Average Day 0 Residue (μg/cm2) 0DAT6: 1.74 0DAT6: 2.48 0DAT6: 1.82

Linear Regression Predicted Day 0 Residue (μg/cm2) 0DAT6: 0.234 0DAT6: 0.296 0DAT6: 0.146

Slope -0.135 -0.149 -0.121

Half-life (days) 5.1 4.7 5.7

R

2 0.7132 0.6271 0.6351

Biphasic Regression Predicted Day 0 Residue (ug/cm2) 0DAT6: 2.3 0DAT6: 3.0 0DAT6: 2.7

Slope -1.587, -1.587 -0.912, -1.588 -2.345, -1.588

Inflection Point (day) 12 12 12