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. Occupationa l 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 Exposu re Assessment

TXRNo.: NA

MRIDNo.: NA

From: Matthew Lloyd, CIH

Risk Assessment Bran ch 57

Health Effects Division (7509 P ) 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 C rowl ey, 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 He alth Effects Division ( HED) conduct an

exposure and risk assessment for the import tolerance assessment of triforine on tomatoes (Mexico) and blueberries (Canada)

. Th is assessme nt includes an update of the registered

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

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

triforin e.

Page I of 14Page 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 Su mmary

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

2.0 Summary of Conclusions and Data Requirements

................................ .............................. 5

3.0 Hazard Characterization

................................ ................................ ................................ ....... 5

4.0 Us e 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

...................... 14Page 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

milde w. 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. T here are no proposed residential uses at this time; however, there are existing residential uses that have been reassessed to reflect updat es to HED’s 2012 Residential SOPs 1 along 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 acu te oral, dermal, and inhalation toxicity, Category I II 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 f or 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 to xicity 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 e stimates were not a concern for any

of the scenarios considered. T he 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 post

application 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

inh alation 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.htmlPage 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) databa se; 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 Studie s Review Board. Descriptions of data sources, as well as guidance on their use, can be found at the Agency website 2

.

2.0 Summary of Conclusions and Data Requirements

There are no occupational/residential risk estimates of concern associated with the p roposed 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 LD 50 > 5000 mg/kg IV

870.1200 Acute dermal [rabbit] 42172702 LD 50 >2000 mg/kg III

870.1300 Acute inhalation [rat] 42172703 LC 50 > 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/pesticid es/science/handler

- exposure

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

- app

- exposure

- data.htmlPage 6 of 14

The toxicological doses and endpoints supporting this action remain unchanged from the previous human health risk assessment (DP 339610

, C

. Olinger , 0 3 / 11 /20 08 ). 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

Intermediate

Term (1

- 6 months) Based on the use pattern for triforine, incidental oral exposure is not anticipated.

Dermal Short

and

Intermediate

Term 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

Intermediate

Term (1

- 6 months) NOAEL = 2 3

mg/kg/day

(inhalation and

oral toxicity are assumed to be equivalent) UF A = 10x

UF H =10x Residential

LOC for MOE

= 100 Subchronic/ chronic oral toxicity study

– dog

LOAEL = 1 2 0 mg/kg/day, based on decreased RBC, hematocrit, hemoglobi n 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 retreat ments 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. 2 5 & 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

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

that have been reassessed from the last human health risk assessment 3 to reflect updates to
HED’s 2012 Residential SOPs 4 along with policy changes for body wei ght 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 as sumed 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/ a pplying liquid concentrates wit h hose

- end sprayer; (2) Mixing/loading/applying liquid concentrates with a manually pressurized handwand

sprayer ; (3) Mixing/loading/ a pplying 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.htmlPage 8 of 14

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

handler risk assessments. Each a ssumption 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 SOPs 5

.

Body Weight:

Since the dermal and inhalation PODs are no t 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 equiv alent 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 SOPs 6 and in Appendix A of this document.

Summary of Resident ial 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 estim ates 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.htmlPage 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

Rate 1 Area Treated or

Amount Handled Daily 2 Inhalation

Dose (mg/kg/day) 3 MOE s 4

(no respiratory protection)

Mixer/Loader/Applicator Manually

pressurized

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

, 7 00,000 Backpack 100 0.14 0.0021 5 gallons 0.000018 1,300,000 Sprinkler can 100 0.0014 0.00 21 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 arou nd 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.

Additiona lly, the mouthing behaviors of children are also commonly addressed in post

application assessments as well as possible inhalation exposures. For triforine, a quantitative
post

- application exposure assessment was not conducted because (1) the primary use s 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 Resid ential 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 post

application 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 reside ntial 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
MOE 4 Post

- application Exposure

(mg/kg/day) Residential

Post

- application

Total Exposure (mg/kg/day) Residential

Post

application
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 repre sents high

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

. 3 F or adults, r esidential tota l exposure combines the highest dermal and inhalation exposures (Table 4.1.1), where applicable. For young children, total r esidential 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/dayPage 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 application s , but, to a lesser extent, could also be a potential source of exposure from ground application method s 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 othe r 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 plac ed 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 AgDRI FT 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 o f 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.htmPage 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 re

entry exposure). Such exposures may occur when workers enter previousl y 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 o n 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.

A n 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 Tr iforine (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 Residentia l 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 formulation

application 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/ft 2 , lb ai/gal); and A = area treated or amount handled (e.g., ft 2 /day, gal/day).