UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

,.->"' "~.s-.1> OFFICE OF CHEMICAL SAFETY 

i ~ ~ AND POLLUTION PREVENTION 0 ... 

~ ~ «'-s-_., c-~ "'l( PRO~~ 

Date: 01/22/13 

Subject: Triforine. Occupational and Updated Residential Exposure Assessment for a 

Proposed Import Tolerance Use on Blueberries and Tomatoes 

PC Code: 10790 I 

Decision No.: 453199 

Petition No.: 

Risk Assessment Type: OccupationaVResidential Exposure Assessment 

TXRNo.: NA 

MRIDNo.: NA 

From: Matthew Lloyd, CIH 

Risk Assessment Branch 57 

Health Effects Division (7509P) 

DP Barcode: 0408358 

Registration No.: IE7911 

Regulatory Action: 

Case No.: 

CAS No.: 26644-46-2 

40CFR: 

Through: Michael Metzger, Branch Chief 4 f /) ;j 

Risk Assessment Branch 57 1/vf.ttv{/f r 

Health Effects Division (7509P) 

To: 

Introduction 

and 

Matt Crowley, Biologist 

Kristin Rury, Biologist Y.- . Exposure Science Advisory Commi .. ~._...... 

Heather Garvie, Risk Manager 

Mary Waller, Team Leader 

Cynthia Giles-Parker, Chief 

Fungicide-Herbicide Branch 

Registration Division (7505P) 

The Registration Division (RD) requested that the Health Effects Division (HED) conduct an 

exposure and risk assessment for the import tolerance assessment of triforine on tomatoes 

(Mexico) and blueberries (Canada). This assessment includes an update of the registered 

residential uses using the revised Residential Standard Operating Procedures (SOPs). This 

revised assessment will be incorporated into the aggregate human health exposure assessment for 

triforine. 

Page I of 14 
Page 2 of 14

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 Outdoor 

Residential Exposure Task Force (ORETF) database; the Residential SOPs (gardens). 

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 11/29/12.
Page 3 of 14

Table of Contents

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

2.0 Summary of Conclusions and Data Requirements .............................................................. 5

3.0 Hazard Characterization....................................................................................................... 5

4.0 Use Profile ........................................................................................................................... 6

5.0 Residential Exposure and Risk Estimates............................................................................ 7

5.1 Residential Handler Exposure/Risk Estimates................................................................. 7

5.2 Residential Post-application Exposure/Risk Estimates.................................................. 10

5.3 Residential Risk Estimates for Use in Aggregate Assessment ...................................... 10

5.5 Spray Drift...................................................................................................................... 12

6.0 Occupational Exposure and Risk Estimates ...................................................................... 12

6.1 Occupational Handler Exposure/Risk Estimates............................................................ 12

6.2 Occupational Post-application Exposure/Risk Estimates .............................................. 13

Appendix A. Summary of Residential Handler and Post-application Algorithms...................... 14
Page 4 of 14

1.0 Executive Summary

Triforine is a piperazine derivative used as a systemic fungicide with protectant, eradicant, and 

curative characteristics. Triforine is registered for use on ornamentals including roses, trees, 

herbaceous plants, and woody shrubs and vines. Products containing triforine are applied by 

aerosol spray, hose-end sprayer, and tank-type sprayer to control black spot, rust, and powdery 

mildew. As a general use pesticide, triforine may be applied around the home by individuals or 

professional applicators. A quantitative occupational assessment is not required because triforine 

has been proposed for use an import tolerance only; therefore is not applied to tomatoes and 

blueberries in the United States, eliminating the potential for occupational exposure. There are 

no proposed residential uses at this time; however, there are existing residential uses that have 

been reassessed to reflect updates to HED’s 2012 Residential SOPs1along with policy changes 

for body weight assumptions. The revision of residential exposures will impact the human 

health aggregate risk assessment for triforine. 

Triforine is classified as Toxicity Category IV for acute oral, dermal, and inhalation toxicity, 

Category III for acute dermal and for skin and eye irritation potential. Triforine is not a dermal 

sensitizer. Triforine has been classified as “Not Likely to be Carcinogenic to Humans”, 

therefore, there is no concern over cancer risk with the proposed or existing uses.

Endpoints have been selected to assess residential exposures to triforine. Toxicity attributed to a 

single dose of triforine was not observed in the database, and acute dietary exposure is not 

expected, so quantification of acute exposures to triforine is not required. Quantification of 

dermal exposures is not required because no toxicity was observed at the limit dose in a

subchronic dermal toxicity study. Endpoints for all inhalation risk assessments were selected 

from oral toxicity studies, so it is assumed that oral and inhalation absorption are equivalent. For 

short- and intermediate-term inhalation exposures an endpoint was selected from subchronic and 

chronic toxicity studies in dogs in which various liver and blood effects were observed.

A quantitative occupational assessment is not required for import tolerance actions. The 

quantitative residential exposure assessment was completed for the inhalation exposures that an 

applicator might receive using both PHED data and exposure data from the Outdoor Residential 

Task Force. There is no concern for dermal exposures because a dermal endpoint of concern 

was not identified in the hazard assessment. Inhalation risk estimates were not a concern for any 

of the scenarios considered. The calculated margins of exposure (MOEs) were several orders of 

magnitude higher than the target level of 100 without respiratory protection. Post-application 

exposure to triforine is not of concern. Like the handler assessment, a quantitative postapplication dermal exposure assessment was not conducted, as no dermal hazard was identified. 

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

inhalation exposure assessment was not performed for triforine 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 triforine. Incidental oral exposure is not 

anticipated because all uses are on ornamental plants where routine contact by children is 

unlikely.

 

1 Available: http://www.epa.gov/pesticides/science/residential-exposure-sop.html
Page 5 of 14

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 

PHED 1.1; the Outdoor Residential Exposure Task Force (ORETF) database; the 

Residential SOPs, 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. 

2.0 Summary of Conclusions and Data Requirements

There are no occupational/residential risk estimates of concern associated with the proposed new 

uses of triforine. 

Residue Data Requirements

No occupational or residential residue data requirements are applicable to this action as an 

import tolerance. In addition, no hazard was identified via the dermal route of exposure because 

of the lack of systemic toxicity following 21 days of dermal exposure to rats at dose levels up to 

1100 mg/kg/day, which is greater than the limit dose. 

3.0 Hazard Characterization

Acute Toxicity

Table 3.0 Acute Toxicity Profile - Triforine 

Guideline 

No. Guideline No.

Guideline 

No. Guideline No. Guideline No.

870.1100 Acute oral [rat] 42172701 LD50 > 5000 mg/kg IV

870.1200 Acute dermal [rabbit] 42172702 LD50 >2000 mg/kg III

870.1300 Acute inhalation [rat] 42172703 LC50 > 5.12 mg/L IV

870.2400 Acute eye irritation [rabbit] 42380407 Conjunctival redness in 1 

rabbit at 24 hrs. [score 1]; 

cleared by 48 hrs.

III

870.2500 Acute dermal irritation [rabbit] 42380408 not an irritant IV

870.2600 Skin sensitization [guinea pig] 42380409 

43396901

not a dermal sensitizer N/A

Toxicological PODs Used for Risk Assessment

 

2

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 14

The toxicological doses and endpoints supporting this action remain unchanged from the 

previous human health risk assessment (DP339610, C. Olinger, 03/11/2008). A summary of the 

endpoints used in the residential exposure assessment are included below in Table 3.1

Table 3.1 Summary of Toxicological Doses and Endpoints for Triforine for Use in Dietary 

and Non-Occupational Human Health Risk Assessments

Exposure/

Scenario

Point of 

Departure

Uncertainty

Factors

Level of 

Concern for 

Risk 

Assessment

Study and Toxicological Effects

Incidental Oral 

Short-Term (1-

30 days) and 

IntermediateTerm (1-6 

months)

Based on the use pattern for triforine, incidental oral exposure is not anticipated.

Dermal Shortand 

IntermediateTerm 

No risk is expected from this exposure scenario because no hazard was identified at the limit dose

in a 21-day dermal toxicity study.

Inhalation 

Short-Term (1-

30 days) and 

IntermediateTerm (1-6 

months)

NOAEL = 23

mg/kg/day

(inhalation and 

oral toxicity are 

assumed to be 

equivalent)

UFA= 10x

UFH=10x

Residential 

LOC for MOE 

= 100

Subchronic/chronic oral toxicity study – dog

LOAEL = 120 mg/kg/day, based on decreased 

RBC, hematocrit, hemoglobin values, increased 

spleen weight, and siderosis in the liver, spleen, 

and bone marrow

Cancer (oral, 

dermal, 

inhalation)

Classification: “Suggestive Evidence of Carcinogenicity” based on two adequate rodent 

carcinogenicity studies. Quantification of human carcinogenic risk is not required for triforine.

Since no inhalation absorption data are available, toxicity by the inhalation route is considered to 

be equivalent to the estimated toxicity by the oral route of exposure.

4.0 Use Profile 

Triforine is registered for use in residential settings by professional applicators or home 

applicators at a maximum application rate of 0.0021 lb ai/gallon of finished spray, or for aerosols 

“as needed.” Depending on the product, several retreatments can be made at 7-10 day intervals.

Table 4 summarizes the use pattern.
Page 7 of 14

Table 4 - Summary of Registered Triforine Residential Uses

Crop Target Formulations Maximum Application Rate and

Frequency of Application

Application 

Equipment

Ornamentals

Fungal 

diseases 

(powdery 

mildew, 

black spot, 

rust)

Liquid 

concentrates

(3.25 & 6.5 

percent)

&

Aerosol can 

(0.1%)

0.0021 lb triforine/gallon of 

finished spray or 0.46 lb ai/acre for 

liquid sprays

&

Aerosols are applied as needed

Retreatments can be made at 3-4 or 

7-10 days depending on the product

hose-end sprayers, low 

pressure handwand 

sprayers, sprinkling 

cans, backpacks

(limited use expected), 

and aerosol cans

5.0 Residential Exposure and Risk Estimates

There are no proposed residential uses at this time; however, there are existing residential uses 

that have been reassessed from the last human health risk assessment3to reflect updates to 

HED’s 2012 Residential SOPs4along with policy changes for body weight assumptions. The 

revision of residential exposures will impact the human health aggregate risk assessment for 

triforine. 

5.1 Residential 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 tasks related to applications and that 

exposures can vary depending on the specifics of each task. Residential handlers are addressed 

somewhat differently by HED as homeowners are assumed to complete all elements of an 

application without use of any protective equipment.

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

following scenarios: 

(1) Mixing/loading/applying liquid concentrates with hose-end sprayer;

(2) Mixing/loading/applying liquid concentrates with a manually pressurized handwand 

sprayer;

(3) Mixing/loading/applying liquid concentrates with garden backpack sprayer

(4) Mixing/loading/applying liquid concentrates with sprinkler can

(5) Applying with aerosol can, and

(6) Applying ready to use sprays with a hose-end sprayer

Residential Handler Exposure Data and Assumptions

 

3 C. Olinger; Triforine: Revised HED Chapter of the Reregistration Eligibility Decision. 3/11/08. D339610. 

4 Available: http://www.epa.gov/pesticides/science/residential-exposure-sop.html
Page 8 of 14

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

handler risk assessments. Each assumption and factor is detailed below.

Application Rate:

The application rates for the various residential use patterns are identified below in Table 5.1.1.

The maximum single application rate for triforine is 0.0021 lbs ai/gallon for foliar application to 

ornamentals.

Unit Exposures and Area Treated or Amount Handled: Unit exposure values and estimates for 

area treated or amount handled were taken from HED’s 2012 Residential SOPs5.

Body Weight: 

Since the dermal and inhalation PODs are not based on developmental and/or fetal effects, the 

body weight appropriate for dermal and inhalation assessments is 80 kg.

Absorption factors: 

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.

Exposure Duration: 

Residential handler exposure is expected to be short-term in duration. Intermediate-term 

exposures are not likely because of the intermittent nature of applications by homeowners.

Residential Handler Non-Cancer Exposure and Risk Estimate Equations

The algorithms used to estimate exposure and dose for residential handlers can be found in the 

2012 Residential SOPs6and in Appendix A of this document.

Summary of Residential Handler Non-Cancer Exposure and Risk Estimates

Since there are no toxicity findings for the short-term dermal route of exposure up to the limit 

dose, the residential handler assessment only includes the inhalation route of exposure. Handler 

risk estimates for all scenarios are not of concern.

 

5 Available: http://www.epa.gov/pesticides/science/residential-exposure-sop.html

6 Available: http://www.epa.gov/pesticides/science/residential-exposure-sop.html
Page 9 of 14

 

Table 5.1.1: Residential Handler Non-cancer Exposure and Risk Estimates for Triforine.

Exposure Scenario Level of 

Concern

Inhalation Unit Exposure

(ug/lb ai)

Maximum 

Application 

Rate1

Area Treated or 

Amount 

Handled Daily2

Inhalation

Dose

(mg/kg/day)3

MOEs

4

(no respiratory 

protection)

Mixer/Loader/Applicator

Manuallypressurized 

handwand 

100 0.018 0.0021 5 gallons 0.0000024 9,700,000

Hose-end Sprayer 100 0.0014 0.0021 11 gallons 0.0000004 5,700,000

Backpack 100 0.14 0.0021 5 gallons 0.000018 1,300,000

Sprinkler can 100 0.0014 0.0021 5 gallons 0.00000018 130,000,000

Aerosol can 100 3 0.000875 2 cans 0.000066 350,000

Hose-end Sprayer 100 0.034 0.0021 11 gallons 0.0000098 2,300,000

1 Based on registered use pattern (D339610).

2 2012 Residential SOPs.

3

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 or gallons/day) / BW (kg).

4

Inhalation MOE = Inhalation NOAEL (mg/kg/day) / Inhalation Dose (mg/kg/day).
Page 10 of 14

5.2 Residential Post-application Exposure/Risk Estimates

The Agency uses a series of pre-defined scenarios to address exposures in the residential 

environment. All types of exposures are considered that can result from the application of a 

pesticide chemical in and around the home as well as in other areas where exposures in the 

general population can occur such as parks and playgrounds. For triforine, no dermal endpoints 

of concern were identified so there is no concern for post-application dermal exposures. 

Additionally, the mouthing behaviors of children are also commonly addressed in postapplication assessments as well as possible inhalation exposures. For triforine, a quantitative 

post-application exposure assessment was not conducted because (1) the primary uses of triforine 

are for disease control on roses and other ornamental plants where children would not be 

expected to routinely contact treated plants and engage in mouthing behaviors which is described 

in the Agency’s Standard Operating Procedures For Residential Exposure Assessment (i.e., 

SOPs); and (2) triforine is relatively non-volatile which, coupled with the dilution expected 

outdoors and the small amounts of active ingredient used diminish the possibility of postapplication inhalation exposure (i.e., also described in Agency’s SOPs). Therefore, there is no 

concern for post-application exposures to triforine. 

5.3 Residential Risk Estimates for Use in Aggregate Assessment

For the purpose of the triforine aggregate human health risk assessment, a summary of the most 

health-protective residential exposure estimates for all registered residential uses are provided in 

Table 5.3. Based on the residential use profile and the 2012 Revised Residential SOPs, only 

short-term inhalation residential handler (for adults) should be included in the aggregate risk 

assessment. The residential contribution to the aggregate is the handler aerosol scenario, 

reflecting an individual using 2 cans of aerosol spray a day over the short-term exposure duration 

(up to 30 days).
Page 11 of 14

Table 5.3. Recommendations for the Residential Exposures for the Triforine Aggregate Assessment.

1

Lifestage

Handler Exposure 

(mg/kg/day)2

Residential

Handler Total 

Exposure 

(mg/kg/day)3

Residential 

Handler 

Total 

MOE4

Post-application Exposure 

(mg/kg/day)

Residential 

Post-application 

Total Exposure 

(mg/kg/day)

Residential 

Postapplication 

MOE Dermal Inhalation Dermal Inhalation Oral

Short-Term

Adult 

Male/Female N/A 0.000066 0.000066 350,000 N/A N/A N/A N/A N/A

1 Bolded risk estimates should contribute to the residential exposure portion of the aggregate assessment. 

2 Handler exposure represents high-end handler exposure (i.e., the highest handler exposure of all scenarios assessed).

3

For adults, residential total exposure combines the highest dermal and inhalation exposures (Table 4.1.1), where applicable. For young children, total residential exposure 

combines high-end post application incidental oral AND dermal exposure, where applicable (Table 4.3.1)

4 Total MOE = Inhalation MOE; Inhalation NOAEL = 23 mg/kg/day
Page 12 of 14

5.5 Spray Drift

Spray drift is always a potential source of exposure to residents nearby to spraying operations. 

This is particularly the case with aerial applications, but, to a lesser extent, could also be a 

potential source of exposure from ground application methods employed for triforine. The 

Agency has been working with the Spray Drift Task Force, EPA Regional Offices and State 

Lead Agencies for pesticide regulation and other parties to develop the best spray drift 

management practices (see the Agency’s Spray Drift website for more information)

7

. On a 

chemical by chemical basis, the Agency is now requiring interim mitigation measures for aerial 

applications that must be placed on product labels/labeling. The Agency has completed its 

evaluation of the new database submitted by the Spray Drift Task Force, a membership of U.S. 

pesticide registrants, and is developing a policy on how to appropriately apply the data and the 

AgDRIFT computer model to its risk assessments for pesticides applied by air, orchard airblast 

and ground hydraulic methods. After the policy is in place, the Agency may impose further 

refinements in spray drift management practices to reduce off-target drift with specific products 

with significant risk estimates associated with drift.

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. 

An occupational exposure assessment is not relevant for the import tolerance of triforine as the 

action doesn’t request a domestic use pattern where HED would assess occupational exposure. 

However, HED most recently assessed occupational handler exposure in the Revised HED 

Chapter of the Reregistration Eligibility Decision Document (RED) for Triforine (D339610). 

Only inhalation risk estimates were quantified and no risks of concern were identified for the 

exposure scenarios. 

 

7 Available: http://www.epa.gov/opp00001/factsheets/spraydrift.htm 
Page 13 of 14

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.

An occupational exposure assessment is not relevant for the import tolerance of triforine. 

However, HED most recently assessed occupational post-application exposure in the Revised 

HED Chapter of the Reregistration Eligibility Decision Document (RED) for Triforine 

(D339610). There is no concern for post-application exposures based on a lack of dermal 

endpoint and low possibility of inhalation exposure for the limited number of possible activities 

that would likely occur.
Page 14 of 14

Appendix A. Summary of Residential Handler and Post-application Algorithms

1.0 Residential Handlers

1.1 Residential Handler Exposure Calculations

1.1.1 Gardens and Trees

Dermal and Inhalation Handler Exposure Algorithm

Daily dermal and inhalation exposure (mg/day) for residential pesticide handlers, for a given 

formulation-application method combination, is estimated by multiplying the formulationapplication method-specific unit exposure by an estimate of the amount of active ingredient 

handled in a day, using the equation below:

E = UE * AR * A

where:

E = exposure (mg/day);

UE = unit exposure (mg/lb ai);

AR = application rate (e.g., lb ai/ft2, lb ai/gal); and

A = area treated or amount handled (e.g., ft2/day, gal/day).