United States			Prevention, Pesticides		EPA 738-R-06-003

			Environmental Protection 		And Toxic Substances		August 2006

			Agency				(7508P)

			_________________________________________________________________

  SEQ CHAPTER \h \r 1 Reregistration Eligibility    Decision for

Triadimefon

And

Tolerance Reassessment for Triadimenol

List B

Case No. 2700

  SEQ CHAPTER \h \r 1

Reregistration Eligibility Decision (RED) Document for Triadimefon

and

Tolerance Reassessment for Triadimenol

Approved by:	___________________

			Debra Edwards, Ph. D.

			Director

			Special Review and Reregistration Division

			Date:	TABLE OF CONTENTS

  TOC \o "1-5" \u  Triadimefon Reregistration Eligibility Decision Team i

Glossary of Terms and Abbreviations	ii

ABSTRACT	1

I.		Introduction	1

II. 	Chemical Overview	3

A.		Regulatory History	3

B.		Chemical Identification	4

    1. 	Technical Triadimefon	4

    2.	Triadimenol	5

    3. 	Triazole Metabolites	5

		  a.  1,2,4-Triazole	6

		  b.  Triazole Alanine	6

		  c.   Triazole Acetic Acid	6

C.		 Use Profile	7

     1.  Triadimefon	7

     2.  Triadimenol	8

D.		 Estimated Usage of Pesticide	9

	    1.	 Triadimefon	9

 	    2.	 Triadimenol	9

III. 	  Summary of Risk Assessments	9

A.	  Human Health Risk Assessment	10

1.	   Toxicity of Triadimefon and Triadimenol	11

		 a.  Acute Toxicity Profile	11

		 b.  FQPA Special Safety Factor Considerations	13

	    c.  Toxicological Endpoints	13

2.    Carcinogenicity	15

3.    Endocrine Effects	16

4.    Dietary Exposure and Risk	16

	    a.  Dietary (Food) Risk Assessment	17

		   1) Acute Dietary Food Risk	17

		   2) Chronic Dietary Food Risk	18

	    b.  Dietary Exposure from Drinking Water	19

	    c.  Dietary Risk from Drinking Water	20

		   1) Acute Dietary Water Risk	20

		   2) Chronic Dietary Water Risk	21

5.    Residential (Non-dietary) Exposure and Risk	22

	    a.  Residential Handler Risk	22

	    b.  Residential Post-application Exposure and Risks	24

6.    Aggregate Exposure/Risk from Triadimefon and Triadimenol	25

7.	   Pesticide and Pharmaceutical Co-Exposure Assessment for the Triazole

	    Metabolites	28

8.	   Cumulative Risk Assessment	29

9.	   Occupational Risk	29

	   a.  Occupational Toxicity	30

	   b.  Occupational Handler Exposure	31

	   c.  Occupational Handler Risk Summary	32

	   d.  Occupational Post-application Risk Summary	37

10. Human Incident Data	37

B.  	      Environmental Fate and Effects Risk Assessment	38

 1.   Environmental Fate and Transport	39

2.   Ecological Exposure and Risk	39	         	   a.  Aquatic Organism Exposure and Risk	40

	   	   1)  Fish, Invertebrate, and Aquatic Plant Toxicity	40

	         2)  Fish and Invertebrate Exposure	42

 	         3)  Fish and Invertebrate Risk	43

	   	   4)  Non-target Aquatic Plants	43

	    b.  Terrestrial Organism Exposure and Risk	44

	         1)  Bird and Mammal Toxicity	44

	  	   2)  Bird and Mammal Exposure	46

	  	   3)  Bird and Mammal Risk	46

	  	   4)  Non-target Terrestrial Plants	48

	         5)  Non-target Insects	49

	      3.   Ecological Incidents	49	      4.   Endangered Species	49

IV.	   Risk Management, Reregistration, and Tolerance Reassessment Decision	49

A.		   Determination of Reregistration Eligibility and Tolerance Reassessment	49

B.		   Public Comments and Responses	50

C.		   Regulatory Position under the FFDCA	50

1.	   Food Quality Protection Act Findings	50

	   a.  “Risk Cup” Determination	50

	   b.   Determination of Safety to U.S. Population	51

	   c.   Determination of Safety to Infants and Children	51

	   d.   Endocrine Disruptor Effects	51

	   e.	   Cumulative Risks	52

	2.   Tolerance Summary for Triadimefon	52

	   a.   Tolerances Currently Listed Under 40 CFR §180.410	52

	   b.   Codex Harmonization	55

	   c.	   Residue Analytical Methods – Plants/Livestock	55

	3.	Tolerance Summary for Triadimenol	56

		   a.  Tolerances Currently Listed Under 40 CFR §180.450	56

D.		   Regulatory Rationale	58

	1.   Human Health Risk Management	59

		   a.   Dietary (Food and Water) Risk Mitigation	59

	   b.   Residential Risk Mitigation	59

	   c.	   Occupational Risk Mitigation	60

	   d.   Aggregate Risk Mitigation for Triazole Metabolites	61

		2.   Environmental Risk Mitigation	61

		3.   Other Labeling	61

		4.   Endangered Species Program	61

V.	    What Registrants Need to Do	62

A.		    Manufacturing Use Products	64

  1.   Generic Data Requirements for Triadimefon	64

  2.   Labeling for Manufacturing Use Products	65

B.		    End-Use Products	65

   1.  Additional Product-Specific Data Requirements	65

   2.  Labeling for End-Use Products	65

C.			Data Requirements for Triadimenol	65

D.		    Labeling Changes Summary Table	66

 VI. 	    Appendices	79

   A.         Use Patterns Subject to Reregistration for Triadimefon	83

   B.         Table of Generic Data Requirements and Studies Used to Make the                             	    Reregistration Decision	83

   C.         Technical Support Documents	94

D.         Citations Considered to be Part of the Data Base Supporting the Reregistration

             Eligibility Decision (Bibliography) for Triadimefon and Triadimenol	97

E.          Generic Data Call-In	114

F.          Product Specific Data Call-In	116

G.          Batching of Triadimenol/Triadimefon Products	118

H.	     List of Registrants Sent this Data Call-In	122

 I.           List of Available Related Documents and Electronically Available Forms	123

      SEQ CHAPTER \h \r 1 Triadimefon Reregistration Eligibility Decision Team  TC "Nitrapyrin Reregistration Eligibility Decision Team" \f C \l "1"

Office of Pesticide Programs:

Biological and Economic Analysis Assessment

Andrew Lee

Jenna Carter

Jin Kim

Tara Chandgoyal

Environmental Fate and Effects Risk Assessment

Michelle Embry

Jonathan Angier

Fred Jenkins

Dana Spatz

Health Effects Risk Assessment

Samuel Ary

Judy Facey

Shanna Recore

Richard Griffin

Michael Doherty

Alan Nielsen

Sheila Piper

Yvonne Barnes

Registration Support

Tony Kish

Risk Management

John W. Pates, Jr.

Kelly Sherman

Veronique LaCapra

Office of General Counsel

Erin Koch

  SEQ CHAPTER \h \r 1 Glossary of Terms and Abbreviations  TC "Glossary of Terms and Abbreviations" \f C \l "1"

AGDCI		Agricultural Data Call-In

ai			Active Ingredient

aPAD			Acute Population Adjusted Dose

AR			Anticipated Residue

BCF			Bioconcentration Factor

CFR			Code of Federal Regulations

cPAD			Chronic Population Adjusted Dose

CSF			Confidential Statement of Formula

CSFII			USDA Continuing Surveys for Food Intake by Individuals

DCI			Data Call-In

DEEM			Dietary Exposure Evaluation Model

DFR			Dislodgeable Foliar Residue

DWLOC		Drinking Water Level of Comparison.

EC			Emulsifiable Concentrate Formulation

EEC			Estimated Environmental Concentration

EPA			Environmental Protection Agency

EUP			End-Use Product

FDA			Food and Drug Administration

FIFRA			Federal Insecticide, Fungicide, and Rodenticide Act

FFDCA		Federal Food, Drug, and Cosmetic Act

FQPA			Food Quality Protection Act

FOB			Functional Observation Battery

G			Granular Formulation

GENEEC		Tier I Surface Water Computer Model

GLN			Guideline Number

HAFT			Highest Average Field Trial

IR			Index Reservoir

LC50			Median Lethal Concentration.  A statistically derived concentration of a substance that can be expected to cause death in 50% of test animals.  It is usually expressed as the weight of substance per weight or volume of water, air or feed, e.g., mg/l, mg/kg or ppm.

LD50			Median Lethal Dose.  A statistically derived single dose that can be expected to cause death in 50% of the test animals when administered by the route indicated (oral, dermal, inhalation).  It is expressed as a weight of substance per unit weight of animal, e.g., mg/kg.

LOC			Level of Concern

LOD			Limit of Detection

LOAEL		Lowest Observed Adverse Effect Level

MATC			Maximum Acceptable Toxicant Concentration

g/g			Micrograms Per Gram

g/L			Micrograms Per Liter

mg/kg/day		Milligram Per Kilogram Per Day

mg/L			Milligrams Per Liter

MOE			Margin of Exposure

MRID			Master Record Identification (number).  EPA's system of recording and tracking studies submitted.

MUP			Manufacturing-Use Product

NA			Not Applicable

NAWQA		USGS National Water Quality Assessment

NPDES		National Pollutant Discharge Elimination System

NR			Not Required

NOAEL		No Observed Adverse Effect Level

OP			Organophosphate

OPP			EPA Office of Pesticide Programs

OPPTS		EPA Office of Prevention, Pesticides and Toxic Substances

PAD			Population Adjusted Dose

PCA			Percent Crop Area

PDP			USDA Pesticide Data Program

PHED			Pesticide Handler's Exposure Data

PHI			Preharvest Interval

ppb			Parts Per Billion

PPE			Personal Protective Equipment

ppm			Parts Per Million

PRZM/EXAMS	Tier II Surface Water Computer Model

Q1*			The Carcinogenic Potential of a Compound, Quantified by the EPA's Cancer Risk Model

RAC			Raw Agriculture Commodity

RED			Reregistration Eligibility Decision

REI			Restricted Entry Interval

RfD			Reference Dose

RQ			Risk Quotient

SCI-GROW		Tier I Ground Water Computer Model

SAP			Science Advisory Panel

SF			Safety Factor

SLC			Single Layer Clothing

SLN			Special Local Need  (Registrations Under Section 24(c) of FIFRA)

TGAI			Technical Grade Active Ingredient

TRR			Total Radioactive Residue

USDA			United States Department of Agriculture

USGS			United States Geological Survey

UF			Uncertainty Factor

UV			Ultraviolet

WPS			Worker Protection Standard

  SEQ CHAPTER \h \r 1 ABSTRACT

	The Environmental Protection Agency (EPA or the Agency) has completed the human health and environmental risk assessments for triadimefon and the dietary and aggregate assessments for triadimenol, and is issuing its risk management reregistration decision and tolerance reassessment.  The risk assessments, which are summarized below, are based on the review of the required target database supporting the use patterns of currently supported products and additional information received through the public docket.

	The Agency discussed the dietary risks of concern (food + water) with the registrant, and the registrant has proposed a number of changes to its triadimefon registration including the voluntary deletion of all food (except pineapples) and residential turf use, and a reduction of application rates and frequencies.  In doing so, this document has estimated exposure and risk based on these new use patterns.

	After considering the risks identified in the revised risk assessments, comments received, and mitigation suggestions from interested parties, the Agency developed its risk management reregistration decision for uses of triadimefon and tolerance reassessment for triadimenol.  As a result of this review, EPA has determined that triadimefon-containing products are eligible for reregistration, provided that risk mitigation measures are adopted and labels are amended accordingly.  Furthermore, the tolerances for triadimefon and triadimenol are considered reassessed and regulatory action under the Federal Food, Drug and Cosmetic Act (“FFDCA”) will occur after the uses that do not meet the Federal Insecticide, Fungicide, and Rodenticide Act (“FIFRA”) standard are canceled.  These decisions are discussed fully in this document.

  SEQ CHAPTER \h \r 1   SEQ CHAPTER \h \r 1 I. 	Introduction  TC "I.  Introduction" \f C \l "1"

FIFRA was amended in 1988 to accelerate the reregistration of products with active ingredients registered prior to November 1, 1984.  The amended Act calls for the development and submission of data to support the reregistration of an active ingredient, as well as a review of all submitted data by the EPA.  Reregistration involves a thorough review of the scientific database underlying a pesticide's registration.  The purpose of the Agency's review is to reassess the potential risks arising from the currently registered uses of the pesticide, to determine the need for additional data on health and environmental effects, and to determine whether or not the pesticide meets the "no unreasonable adverse effects" criteria of FIFRA.

On August 3, 1996, the Food Quality Protection Act of 1996 (FQPA) was signed into law.  This Act amends FIFRA and the FFDCA to require reassessment of all existing tolerances for pesticides in food.  FQPA also requires EPA to review all tolerances in effect on August 2, 1996, by August 3, 2006.  In reassessing these tolerances, the Agency must consider, among other things, aggregate risks from non-occupational sources of pesticide exposure, whether there is increased susceptibility to infants and children, and the cumulative effects of pesticides with a common mechanism of toxicity.  When a safety finding has been made that aggregate risks are not of concern and the Agency concludes that there is a reasonable certainty of no harm from aggregate exposure, the tolerances are considered reassessed.  EPA decided that, for those chemicals that have tolerances and are undergoing reregistration, tolerance reassessment will be accomplished through the reregistration process.

  SEQ CHAPTER \h \r 1 As mentioned above, FFDCA requires that the Agency consider “available information” concerning the cumulative effects of a particular pesticide’s residues and “other substances that have a common mechanism of toxicity” when considering whether to establish, modify, or revoke a tolerance.  Potential cumulative effects of chemicals with a common mechanism of toxicity are considered because low-level exposures to multiple chemical substances that cause a common toxic effect by a common mechanism of toxicity could lead to the same adverse health effect that would occur at a higher level of exposure to any one of these individual chemicals.  Triadimefon belongs to a group of pesticides called triazoles (or conazoles), which also includes the triazole fungicide subject to reregistration, propiconazole.  Triadimenol, a metabolite of triadimefon, is also a registered fungicide and is subject to tolerance reassessment.  For the purpose of this reregistration eligibility decision (RED) for triadimefon and tolerance reassessment for triadimenol, EPA has concluded that triadimefon and triadimenol do not share a common mechanism of toxicity with other substances.  However, the triazole fungicides share common metabolites, the triazole compounds 1,2,4-triazole (free triazole), triazole alanine, and triazole acetic acid, which are considered in this document.  For information regarding EPA’s efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the policy statements released by EPA’s Office of Pesticide Programs concerning common mechanism determinations and procedures for cumulating effects from substances found to have a common mechanism on EPA’s website at   HYPERLINK "http://www.epa.gov/pesticides/cumulative"  http://www.epa.gov/pesticides/cumulative .

The Agency has identified triazole metabolites of toxicological concern; these include 1,2,4-triazole and the conjugates triazole alanine and triazole acetic acid. Because these metabolites are formed from all triazole pesticides, EPA has conducted a separate toxicology assessment for these compounds and concluded that the existing data are sufficient to support the reregistration of triadimefon and triadimenol.  For more details on the toxicity of the free triazoles, see the August 5, 2003, documents, TRIAZOLES – Report of the Ad Hoc HED Peer Review Committee, TRIAZOLES – 2nd Report of the Ad Hoc HED Peer Review Committee, and the February 7, 2006, document, 1,2,4-Triazole, Triazole Alanine, Triazole Acetic Acid: Human Health Aggregate Risk Assessment in Support of Reregistration and Registration Actions for Triazole-derivative Fungicide Compounds, which are available under docket number EPA-HQ-OPP-2005-0258.  Because the risks associated with the free triazoles are all below the Agency’s level of concern, they are not discussed further in this document.  For more information regarding the aggregate assessment of free triazoles, see the July 18, 2006, document, Reregistration Eligibility Decision (RED) for Propiconazole, in the Agency’s electronic docket on the internet at   HYPERLINK "http://www.regulations.gov"  http://www.regulations.gov  under docket number EPA-HQ-OPP-2005-0497.

Triadimefon and triadimenol also share a common metabolite, 1,2,4-triazole, with several triazole-derivative pharmaceutical compounds.  Thus, EPA must consider the incremental impact of exposure to 1,2,4-triazole pesticide residues to individuals using triazole-derivative pharmaceutical products.  To this end, EPA worked with the U.S. Food and Drug Administration (FDA), which has regulatory authority for drug products, to assess the risks posed by 1,2,4-triazole residues that could result from concurrent exposure to triazole-derivative pharmaceutical and pesticide products.  This assessment will provide the basis of safety findings reflecting the joint perspectives of FDA and EPA, and will inform a decision by both Agencies about whether appropriate measures are needed to reduce exposure from one or both sources of 1,2,4-triazole residues.

This document presents a summary of EPA’s revised human health and ecological risk assessments, its reregistration eligibility decision for triadimefon and tolerance reassessment decision for triadimenol.  Occupational and ecological risks from exposure to the pesticidal uses of triadimenol are not addressed in this document.  The document consists of six sections. Section I contains the regulatory framework for reregistration/tolerance reassessment.  Section II provides a profile of the use and usage of the chemicals.  Section III gives an overview of the revised human health and environmental effects risk assessments based on data, public comments, and other information received in response to the preliminary risk assessments.  Section IV presents the Agency’s reregistration eligibility, risk management and tolerance reassessment decisions.  Section V summarizes label changes necessary to implement the risk mitigation measures outlined in Section IV.  Finally, the Appendices list related and supporting documents.  The revised risk assessments for triadimefon and triadimenol are available in the Agency’s electronic docket on the internet at   HYPERLINK "http://www.regulations.gov"  http://www.regulations.gov  under docket number EPA-HQ-OPP-2005-0258 and EPA-HQ-OPP-2006-0038, respectively.

II. 	Chemical Overview  TC "II. 	Chemical Overview" \f C \l "1"

	A.	Regulatory History  TC "A.	Regulatory History" \f C \l "2"

Triadimefon

 Triadimefon is a broad spectrum, systemic fungicide used to control rust and mildew on apples, grapes, pears, pineapples, and raspberries.  In addition, it is used to control various fungal diseases on non-food use sites such as pine seedlings, Christmas trees, residential and commercial turf, ornamentals, and landscapes.  There are tolerances for triadimefon on apples, grapes, pears, pineapples, and raspberries.  Triadimefon end-use products are marketed in the United States under the trade names Bayleton and Summit.  There are nineteen active products containing triadimefon (one technical product) registered under Section 3 of FIFRA.

The registrant has agreed to delete all food (except pineapple) and residential turf uses.  Therefore, this Reregistration Eligibility Decision document evaluates risks from all currently supported uses of triadimefon.  The Agency will follow the FIFRA cancellation with the appropriate tolerance revocations.

Triadimenol

The primary metabolite of triadimefon is triadimenol.  Triadimenol, which degrades to include the metabolites KWG 1323 and KWG 1342, is also registered separately as a broad spectrum, systemic fungicide under its own active ingredient number (PC code: 127201).  Triadimenol is used exclusively in the U.S. as a seed treatment for cotton and grains.  As a result, it is also being assessed by the Agency for the purposes of a tolerance reassessment eligibility decision (TRED).  Triadimenol was first registered after 1984 and is not subject to reregistration under the 1988 amendments to FIFRA.

Chemical Identification

1.	Technical Triadimefon

  TC "B. 	Chemical Identification" \f C \l "2"

Common Name:		Triadimefon

Chemical Name: 1-(4-chlorophenoxy)-3,3-dimethyl-1-(1H-1,2,4-triazol-1-yl)-2-butanone

Chemical Family:		Azole (Triazoles)

Empirical Formula:		  SEQ CHAPTER \h \r 1 C14H16CLN3O2

CAS Registry Number:	43121-43-3

Case Number:		2700

OPP Chemical Code: 	109901

Molecular weight:		293.75 g/mol

Trade Names:		Bayleton and Summit

Basic Manufacturers:	Bayer CropScience, LC

Triadimefon has a melting point of 82.3 degrees Celsius, a solubility of 64 mg/L ppm in water 20 degrees Celsius and a vapor pressure of 0.2 – 0.6 mPa at 20 and 25 degrees Celsius, respectively (7.6 x 10-7 mm Hg).

2.	Triadimenol

Common Name:		Triadimenol

Chemical Name:		 [beta-(4-chlorophenoxy)-alpha-(1,1-dimethylethyl)-1H-1,2,4-					 triazole-1-ethanol]

Chemical Family:		Azole (Triazoles)

Empirical Formula:		C14H18ClN3O2

  SEQ CHAPTER \h \r 1

CAS Registry Number:		55219-65-3

Case Number:		2700

OPP Chemical Code: 		127201

Molecular weight:		295.77 g/mol

Trade Names:		Baytan

Basic Manufacturers:	Bayer CropScience, LC

	Triazole Metabolites

Triadimefon, triadimenol, and other triazole fungicides are metabolized in animals and plants to form compounds containing the triazole moiety, including 1,2,4-triazole (free triazole), triazole alanine, and triazole acetic acid, which are also considered in this decision.  Since triazole alanine and triazole acetic acid are formed by conjunction with an amino acid, they are referred to as triazole conjugates throughout this document.  Chemical information for these triazole metabolites is provided below.

a.	1,2,4-Triazole

Chemical Name:	1,2,4-Triazole

Common Name(s):	1,2,4-T; free triazole

CAS Number:	288-88-0

PC Code:		600074

Molecular Weight:	69.07

Triazole Alanine

Chemical Name:	Triazole Alanine (TA)

CAS No.:	86362-20-1

PC Code:	600011

Molecular Weight:	156.15

Triazole Acetic Acid

Chemical Name: 	Triazole Acetic Acid (TAA)

CAS No.:		28711-29-7

PC Code:		600082

Molecular Weight:	127.10

  SEQ CHAPTER \h \r 1 C. 	Use Profile  TC "C. 	Use Profile" \f C \l "2"

Triadimefon

The following is information on the currently registered uses of triadimefon, including an overview of use sites and application methods.  A detailed table of the uses of triadimefon eligible for reregistration is contained in Appendix A.

Type of Pesticide:  	Broad spectrum, systemic fungicide; demethylation inhibitor (DMI).

Summary of Use:	Used for the systemic control of various fungal diseases in fruits, turf, pine seedlings, Christmas trees, and ornamentals.

Food uses:			Apples, grapes, pears, pineapples, and raspberries.

					(Registrant is voluntarily deleting use on apples, grapes, 				 pears, and raspberries).

Non-food uses:	Pine seedlings, Christmas trees, residential and commercial turf, ornamentals, and landscapes.

	(Registrant is voluntarily deleting residential turf use).

Formulation Type: 	Registered formulations include granular (G)(0.5-1% active ingredient), wettable powder (WP)(25-50% active ingredient), water soluble packets (50% active ingredient), liquid concentrate (LC)(0.88% active ingredient), and ready-to-use (RTU)(0.5% active ingredient).

Registrant(s):	Bayer CropScience, LP

Method and Rates of Application:

Application Methods:	Applied via ground spray, airblast, aerial spray , chemigation, and broadcast (granular only) to apples, pears, raspberries, grapes, Christmas trees, ornamentals, pine seedlings, and turf (golf course, residential, commercial, and recreational).  It is also used as a post-harvest dip for pineapples and as a seed-piece treatment prior to planting. It is also used to treat pine seeds via dip, soak, or traditional seed treatment.

Application Rates: 	The registrant has agreed to voluntarily delete all food (except pineapple) and residential turf use.

	Current maximum application rates are a 5.4 lb. ai/A treatment on turf (California only) and a 2.7 lb. ai/A treatment on turf outside of California.  A maximum rate of 0.75 lbs ai/A may be used as a pre-harvest foliar treatment on apples and pears (up to 12X per season), 0.56 lbs ai/A for grapes (up to 6X per season), and 0.88 lbs ai/A for raspberries (up to 7X per season).  A maximum rate of 2.0 lbs ai/A may be used for pre-harvest foliar treatment on both Christmas trees (up to 8X per season) and pine seedlings (up to 16X per season).  For pineapple, a maximum rate of 0.28 lbs ai/100 gallons solutions may be applied via dip and at a maximum rate of 0.28 lbs ai/100 gallons solution via dip or spray to the whole fruit following harvest.  It is also used as a pine seed soak (0.63 lbs ai/100 gal solution), and as a pine seed treatment (0.063 lbs ai/100 gal solution, one time prior to planting.

Application Timing:  	Applied pre-plant, foliar and post-harvest.

Use Classification:	General

		2.	Triadimenol

The following is information on the currently registered uses of triadimenol, including an overview of use sites and application methods.  A detailed table of the uses of triadimenol eligible for tolerance reassessment is contained in Appendix A.

Type of Pesticide:  	Systemic fungicide for seed treatment.

Summary of Use:	Used as a seed treatment on: barley, corn, cotton, oats, rye, sorghum, and wheat.  There is also an import tolerance on bananas.

Formulation Type: 	Registered formulations include emulsifiable concentrate (EC) (5% active ingredient), wettable powder (WP)(25% active ingredient), soluble concentrate (SC) (13.33% active ingredient), and flowable concentrate (FlC) (28.3 - 30% active ingredient).

Registrant(s):	Bayer CropScience, LP

Method and Rates of Application:

Application Rates: 	The maximum use rates, adjusted for planting, range from 0.006 to 0.0375 lbs. ai/A (0.007-0.042 kg ai/ha) for one season.

Application Timing:  	Applied pre-plant.

Use Classification:	General

	Estimated Usage of Pesticide

1.	Triadimefon  TC "D.	Estimated Usage of Pesticide" \f C \l "2"

Screening level estimates of triadimefon use in the U.S., based on data from the years 1990 through 2000, have been provided by the Agency’s Biological and Economic Analysis Division.  Total use averaged 135,000 lbs ai/year with an upper-end estimate of 266,000 lbs ai/year.  The largest market, in terms of total pounds ai, was seen in the turf and ornamental sector.

2.	Triadimenol

	Based on pesticide usage data for the years 1992 through 2001, total annual domestic usage of triadimenol averaged approximately 24,000 pounds of active ingredient (a.i.) for over 12,000,000 acres treated.  Use on cotton accounted for approximately 75 % of the total pounds of a.i. applied annually.  Corn and wheat accounted for approximately 20% and 5%, respectively.  About 80% of U.S. acreage planted to cotton is treated with triadimenol, and less than 1 % of corn and wheat acres are treated

  SEQ CHAPTER \h \r 1 III. 	Summary of Risk Assessments  TC "III.  Summary of Nitrapyrin Risk Assessments" \f C \l "1"

The following is a summary of EPA's human health and ecological risk findings and conclusions for triadimefon and triadimenol, as presented fully in the documents:

Triadimefon

Triadimefon. Preliminary Human Health Risk Assessment (Revised). February 9, 2006

Triadimefon/Triadimenol: Summary of Refinements and Revisions to the Human Health Risk Assessment.  July 10, 2006

Triadimefon: Revised Acute, Probabilistic and Chronic Dietary (Food + Drinking Water) Exposure and Risk Assessments for the Triadimefon Reregistration.  July 6, 2006

Environmental Fate and Effects Chapter (Revised), Risk Assessment for Triadimefon.  January 19, 2006

Triadimefon: HED Response to Comments Received During the Public Comment Phase.  June 20, 2006

Memo: EFED Revisions to the Ecological Risk Assessment.  August 3, 2006

Triadimefon. Summary of Ana--lytical Chemistry and Residue Data for the Reregistration Eligibility Decision (RED) Document.  November 23, 2005

Triadimefon: Occupational and Residential Exposure Assessment for the Reregistration Eligibility Decision Document.  June 30, 2006

Triadimefon and Triadimenol: Aggregate Acute, Chronic, and Short-Term Risk Assessments Reflecting July, 2006 Risk Mitigation in Response to the Phase 4 Triadimefon RED.  August 1, 2006

Response to Bayer Public Comments Regarding the Environmental Fate and Effects Division Triadimefon Risk Assessment. June 1, 2006

Tier 2 Drinking Water Assessment for Triadimefon and its Major Degradate Triadimenol.  August 31, 2005

Triadimenol

Triadimenol: HED Chapter of the Tolerance Reassessment Eligibility Decision (TRED) Document (Revised).  February 9, 2006

Triadimenol. Acute and Chronic Dietary Exposure Assessments for the Tolerance Reassessment Eligibility Decision (TRED) Document.  November 18, 2005

The purpose of this section is to summarize the key features and findings of the risk assessments in order to help the reader better understand the risk management decisions reached by the Agency.  The human health and ecological risk assessment documents and supporting information listed in Appendix C were used to reach the safety finding and regulatory decisions for triadimefon and triadimenol.  Although the risk assessments and related addenda are not included in this document, they are available from the OPP Public Docket OPP-2005-0258 and OPP-2006-0038, and may also be accessed on the web at   SEQ CHAPTER \h \r 1   HYPERLINK "http://www.regulations.gov"  http://www.regulations.gov .  Hard copies of these documents may be found in the OPP public docket under these same docket numbers.

A.	Human Health Risk Assessment

The human health risk assessment incorporates potential exposure from all sources, which for triadimefon includes food, drinking water, residential, and occupational scenarios and for triadimenol include food and drinking water scenarios.  Aggregate assessments combine food, drinking water, and any residential or other non-occupational (if applicable) exposures to determine potential exposures to the U.S. population.

This document summarizes risk estimates for triadimefon (including its metabolite triadimenol and degradates KWG 1342 and KWG 1732), and its metabolites 1,2,4-triazole, triazole alanine, and triazole acetic acid, which are formed from triazole compounds in animals and plants and may be found in food commodities, including animal byproducts.  1,2,4-Triazole appears to be relatively stable in the environment, and may be found in rotational crops and drinking water.  A surface water monitoring study showed detections of 1,2,4-triazole in a small number of samples.  Therefore, EPA has considered the risks from food, drinking water and non-occupational exposure resulting from triadimefon alone and from the triazole metabolites from all pesticide sources.  For triadimenol, since there are no residential uses, EPA considered exposure and risk from food and drinking water   In addition, EPA has also considered potential co-exposure to free triazoles resulting from pharmaceutical uses of triazole compounds.  Because the risks associated with the free triazoles from all sources are all below the Agency’s level of concern, they are not discussed further in this document.  Additional details regarding the risks associated with the free triazoles, which includes contribution from triadimefon and triadimenol,- may be found in the February 7, 2006, document, 1,2,4-Triazole, Triazole Alanine, Triazole Acetic Acid:  Human Health Aggregate Risk Assessment in Support of Reregistration and Registration Actions for Triazole Derivative Fungicide Compounds, which is available in the public docket (EPA-HQ-OPP-2005-0258).

	1.	Toxicity of Triadimefon and Triadimenol  TC "a.	Toxicity of Nitrapyrin" \f C \l "4"

Toxicity assessments are designed to predict whether a pesticide could cause adverse health effects in humans (including short-term or acute effects such as skin or eye damage, and lifetime or chronic effects such as cancer, developmental and/or reproductive effects), and the level or dose at which such effects might occur.  The Agency has reviewed all toxicity studies submitted and has determined that the toxicity database for triadimefon is adequate although there are data gaps (lack of a developmental neurotoxicity study which the Agency will remedy through the DCI).  In addition, the Agency has reviewed all toxicity studies submitted for triadimenol and has determined that the database is adequate.  The triadimenol data base is less definite than triadimefon; however, because it is a metabolite of triadimefon the Agency believes that the use of data on triadimefon can be used for triadimenol and be protective regarding any potential risk concerns.  Therefore, the Agency is not requiring a developmental neurotoxicity (DNT) study for triadimenol.    SEQ CHAPTER \h \r 1 All other studies have been submitted to support guideline requirements and a reregistration eligibility determination for all currently registered uses.  For more details on the toxicity of triadimefon, see the February 9, 2006, document, Triadimefon. Preliminary Human Health Risk Assessment (Revised), and the July 10, 2006, document, Triadimefon/Triadimenol: Summary of Refinements and Revisions to the Human Health Risk Assessment, which is available under docket number EPA-HQ-OPP-2005-0258.

Acute Toxicity Profile

Triadimefon

Triadimefon is classified as category III for acute oral and dermal toxicity and as category IV for acute inhalation.  It is also classified as category IV for eye irritation potential and category IV for skin irritation potential.  In addition, triadimefon caused dermal sensitization in guinea pigs.  The acute toxicity profile for technical grade triadimefon is summarized in Table 1 below.  The technical acute toxicity values included in this document are only to provide background information.  Additional acute toxicity data may be required to determine appropriate cautionary label language for products containing triadimefon.

Table 1.  Acute Toxicity Profile for Triadimefon

Old Guideline

 No.	New Guideline No.

Study Type

MRID #(s)

Results	Toxicity Category

81-1	870.1100	Acute Oral - rat

264276	LD50 =  1,470 mg/kg (Males)

LD50 =  1,090 mg/kg    (Females)	III

81-2	870.1200	Acute Dermal -

Rabbit	264276	LD50 > 2,000 mg/kg	III

81-3	870.1300	Acute Inhalation - rat

41616002	LC50 > 3.570 mg/L	IV

81-4	870.2400	Acute (Primary) Eye Irritation - rabbit

41782501	Slightly irritating 	IV

81-5 	870.2500	Acute (Primary) Dermal (Skin) Irritation - rabbit

41616004	Not an irritant	IV

81-6	870.2600	Skin (Dermal) Sensitization – guinea pig

41554001	Sensitizer	Not Applicable

Triadimenol

	Triadimenol shows low toxicity for acute oral, dermal, and inhalation exposure  (toxicity Category III or IV) and is not a skin sensitizer.  Triadimenol is an eye irritant with irritation clearing in 21 days or longer (toxicity Category II), and is a mild dermal irritant (toxicity Category IV).  The acute toxicity profile for technical triadimenol is summarized in Table 2 below.

Table 2:  Acute Toxicity Profile for Triadimenol

Old Guideline No.

New Guideline No.

Study Type

MRID #(s)

Results

Toxicity Category

81-1

870.1100

Acute oral –rat

00125411

LD50 = 689 mg/kg (males)

LD50 = 752 mg/kg (females)

III

81-2

870.1200

Acute dermal – rabbit

00145086

LD50 > 2000 mg/kg

III

81-3

870.1300

Acute inhalation – rat

00145087

LC50 > 2.58 mg/L (Limit Dose)

IV

81-4

870.2400

Acute eye irritation – rabbit

00145088

eye irritant. Irritation cleared in 21 days or longer.

II

81-5

870.2500

Acute dermal irritation – rabbit

00145088

mild skin dermal irritation

IV

81-6

870.2600

Skin sensitization- guinea pig

00125413

Not a skin sensitizer

Not Applicable

		b.	FQPA Safety Factor Considerations  TC "b.	FQPA Safety Factor" \f C \l "4"

  SEQ CHAPTER \h \r 1 The FFDCA as amended by the FQPA directs the Agency, in setting pesticide tolerances, to use an additional tenfold (10X) margin of safety to protect infants and children, taking into account the potential for pre- and post-natal toxicity and the completeness of the toxicology and exposure databases.  The statute authorizes the Agency to reduce this tenfold FQPA safety factor (SF) only if reliable data demonstrate that the resulting level of exposure would be safe for infants and children.

Triadimefon

The current developmental and reproductive toxicity studies do not suggest that the young are more sensitive than adult animals.  However, since the triadimefon database does not include a DNT study, an FQPA safety factor for database uncertainty (10X) has been retained for exposure scenarios through which exposure to children or pregnant women is expected.  A DNT study is required for triadimefon and the Agency will issue a DCI for this data.

Triadimenol

	The endpoint of concern for triadimenol, like triadimefon, is neurotoxicity, which was observed in rat, mice, and rabbit studies.  Evidence of increased susceptibility to offspring was not seen in available developmental toxicity studies in two species (rabbits and rats) and in a two-generation reproductive toxicity study in rats.  Therefore, the Agency is not requiring a developmental neurotoxicity (DNT) study for triadimenol at this time, pending the results of the acute and subchronic neurotoxicity studies listed in section V of this document.  However, the Agency is retaining the FQPA Safety Factor (10X) for database uncertainty for lack of both acute and subchronic neurotoxicity studies.

 			c.        Toxicological Endpoints

Triadimefon

Table 3 summarizes the studies, toxicological endpoints, dose levels, and uncertainty/safety factors selected for the assessment of dietary, oral, dermal, and inhalation exposure to triadimefon.  Since no appropriate acute endpoint could be determined from the triadimenol database, the triadimefon subchronic neurotoxicity study in rats was chosen for the acute reference dose (aRfD) for triadimenol, as well.  In addition, the subchronic neurotoxicity study for triadimefon was also chosen for the chronic reference dose (cRfD) for triadimenol.  Therefore, the endpoint of concern is neurotoxicity and is the same for both triadimefon and triadimenol.

Table 3.  Summary of Doses and Toxicological Endpoints for Triadimefon

Exposure

Scenario	Dose, Uncertainty Factors (UF)	FQPA Safety Factor (SF) and Level of Concern

Study and Toxicological Effects

Acute Dietary

(general population)

 NOAEL = 3.4 mg/kg/day (subchronic)

UF = 100

Acute RfD = 0.034 mg/kg/day 	FQPA SF = 10X

aPAD = acute RfD

              FQPA SF

aPAD = 0.0034 mg/kg/day

Subchronic neurotoxicity study in rats (MRID 44153501).

LOAEL = 54.6 mg/kg/day (males) and 68.7 mg/kg/day (females) based largely on hyperactivity.

Chronic Dietary

(all populations)

NOAEL = 3.4 mg/kg/day

UF = 100

Chronic RfD = 0.034 mg/kg/day	FQPA SF = 10X

cPAD = chronic RfD

              FQPA SF

cPAD = 0.0034 mg/kg/day

Subchronic neurotoxicity study in rats (MRID 44153501).

LOAEL = 54.6 mg/kg/day (M) and 68.7 mg/kg/day (F) based largely on hyperactivity.

Incidental Oral Short-Term

(1 - 30 days)

NOAEL = 3.4 mg/kg/day

UF = 100

FQPA SF = 10X

Residential MOE = 1000

Subchronic neurotoxicity study in rats (MRID 44153501).

LOAEL = 54.6 mg/kg/day (M) and 68.7 mg/kg/day (F) based largely on hyperactivity.

Dermal

Short-Term

(1 - 30 days) and

Intermediate-Term

(1 - 6 months)

Dermal NOAEL = 300 mg/kg/day

UF = 100	Residential MOE = 1000

FQPA SF = 10X

Occupational MOE = 100

21 day dermal toxicity in rats (MRID 42341501).

The LOAEL= 1000 mg/kg/day based on increased reactivity and activity in the females.

Inhalation

Short-Term

(1 - 30 days)

NOAEL = 3.4 mg/kg/day

(Inhalation absorption rate = 100%)

UF = 100

Residential MOE = 1000

FQPA SF = 10X

Occupational MOE = 100

Subchronic neurotoxicity study in rats (MRID 44153501).

LOAEL = 54.6 mg/kg/day (M) and 68.7 mg/kg/day (F) based largely on hyperactivity.

Inhalation

Intermediate-Term

(1 - 6 months)

NOAEL = 3.4 mg/ kg/day

(Inhalation absorption rate = 100%)

UF = 100	Residential MOE = 1000

FQPA SF = 10X

Occupational MOE = 100

Subchronic neurotoxicity study in rats (MRID 44153501).

LOAEL = 54.6 mg/kg/day (M) and 68.7 mg/kg/day (F) based largely on hyperactivity.

Cancer (oral, dermal, inhalation)

Classification: Category C (possible human carcinogen) based on statistically significant increase in thyroid adenomas in male Wistar rats and statistically significant increases in hepatocellular adenomas in both sexes of the NMRI mouse.

UF, uncertainty factor; SF, safety factor; NOAEL, no observable adverse effect level; LOAEL, lowest observable adverse effect level; RfD, reference dose, exposure which is not expected to exceed EPA’s level of concern; PAD, population adjusted dose, which is the RfD adjusted for the FQPA safety factor (SF); MOE, margin of exposure; LOC, Level of Concern, MOE at and above which the Agency does not have a risk concern.  NA, Not Applicable.

Triadimenol

Table 4 summarizes the studies, toxicological endpoints, dose levels, and uncertainty/safety factors selected for the assessment of dietary exposure to triadimenol.  The endpoint of concern is neurotoxicity (same as triadimefon).

Table 4.  Summary of Doses and Toxicological Endpoints for Triadimenol

Exposure

Scenario	Dose, Uncertainty Factors (UF)	FQPA Safety Factor (SF) and Level of Concern

Study and Toxicological Effects

Acute Dietary

(general population)

 NOAEL = 3.4 mg/kg/day (subchronic)

UF = 100

Acute RfD = 0.034 mg/kg/day 	FQPA SF = 10X

aPAD = acute RfD

              FQPA SF

aPAD = 0.0034 mg/kg/day

Subchronic neurotoxicity study in rats (MRID 44153501) for triadimefon.

LOAEL = 54.6 mg/kg/day (M) and 68.7 mg/kg/day (F) based largely on hyperactivity.

Chronic Dietary

(all populations)

NOAEL = 3.4 mg/kg/day

UF = 100

Chronic RfD = 0.034 mg/kg/day	FQPA SF = 10X

cPAD = chronic RfD

              FQPA SF

cPAD = 0.0034 mg/kg/day

Subchronic neurotoxicity study in rats (MRID 44153501) for triadimefon.

LOAEL = 54.6 mg/kg/day (M) and 68.7 mg/kg/day (F) based largely on hyperactivity.

Cancer

(oral, dermal, inhalation)	Classification:  Category C “possible human carcinogen” based on increased incidence of hepatocellular adenomas in females.

2.	Carcinogenicity

Triadimefon

The Cancer Assessment Review Committee (CARC) assigned  SEQ CHAPTER \h \r 1  triadimefon a classification of "possible human carcinogen", using the criteria in the Draft Guidelines for Carcinogen Risk Assessment (July, 1999).  This classification is based on a statistically significant increase in thyroid adenomas in male Wistar rats and statistically significant increases in hepatocellular adenomas in both sexes of the NMRI mouse.  However, the Agency concluded that a quantified carcinogenic risk assessment for triadimefon is not appropriate and risk assessment will be based on the chronic population adjusted dose (cPAD) and margin of exposure (MOE) approaches only.

Triadimenol

	The CARC has assigned triadimenol a classification of “possible human carcinogen”, using the criteria in the Draft Guidelines for Carcinogen Risk Assessment (July, 1999).  This classification is based on increased incidence of hepatocellular adenomas in females.  However, the Agency concluded that a quantified carcinogenic risk assessment for triadimenol is not appropriate and risk assessment will be based on the chronic population adjusted dose (cPAD) and margin of exposure (MOE) approaches only.

		3.	Endocrine Effects

EPA is required under the FFDCA, as amended by FQPA, to develop a screening program to determine whether certain substances (including all pesticide active and other ingredients) “may have an effect in humans that is similar to an effect produced by a naturally occurring estrogen, or other such endocrine effects as the Administrator may designate.”  Following recommendations of its Endocrine Disruptor and Testing Advisory Committee (EDSTAC), EPA determined that there was a scientific basis for including, as part of the program, the androgen and thyroid hormone systems, in addition to the estrogen hormone system.  EPA also adopted EDSTAC’s recommendation that the Program include evaluations of potential effects in wildlife.  For pesticide chemicals, EPA will use FIFRA and, to the extent that effects in wildlife may help determine whether a substance may have an effect in humans, FFDCA authority to require the wildlife evaluations.  As the science develops and resources allow, screening of additional hormone systems may be added to the Endocrine Disruptor Screening Program (EDSP).

Triadimefon and Triadimenol

	The toxicity databases for triadimefon and triadimenol did not show any estrogen, androgen, or thyroid mediated toxicity.

		4.	Dietary Exposure and Risk  TC "c.	Population Adjusted Dose" \f C \l "4"

	The registrant has agreed to voluntarily cancel all food (apples, pears, grapes, and raspberries), except pineapple, and residential turf use for triadimefon.  Thus, these uses were not included in this dietary risk assessment.  In addition, the registrant is only supporting a maximum turf rate of 2 applications of 2.7 lbs. ai/A for golf courses and sod farms.  Therefore, all drinking water risk estimates were calculated using this rate.

Dietary risk assessments consider exposure to pesticide residues from both food and drinking water.  In examining dietary risk, exposures from the use of triadimefon, which includes the parent and its metabolites, including triadimenol, as well as exposures from the use of triadimenol, which includes the parent and its metabolites, must be added together.  This is due to the fact that both the acute and chronic PADs are based on the same study (a subchronic neurotoxicity study in rats exposed to triadimefon) and therefore must be aggregated.  To estimate dietary risks from food and drinking water, EPA compares the estimated exposure to pesticide residues in food and drinking water to the acute or chronic population adjusted dose, or PAD.  The PAD is the reference dose (RfD) adjusted for the FQPA safety factor.  A risk estimate that is less than 100% of the acute PAD (aPAD), the dose at which an individual could be exposed over the course of a single day and no adverse health effects would be expected, does not exceed EPA’s level of concern.  Likewise, a risk estimate that is less than 100% of the chronic PAD (cPAD), the dose at which an individual could be exposed over the course of a lifetime and no adverse health effects would be expected, does not exceed EPA’s level of concern. Additional details about the dietary risk assessment for triadimefon and triadimenol are described in the July 6, 2006, document, Triadimefon. Revised Acute and Chronic Dietary (Food + Drinking Water) Exposure and Risk Assessments for the Triadimefon Reregistration and in the February 9, 2006, document, Triadimenol: HED Chapter of the Tolerance Reassessment Eligibility Decision (TRED) Document (Revised).

	Acute PAD.  As discussed in Section III of this document, the Agency used the subchronic neurotoxicity study (SCN) for triadimefon to establish the acute RfD that is used for both chemicals.  The endpoint of concern is neurotoxicity seen after both an acute gavage and repeated dietary exposure.  The NOAEL was 3.4 mg/kg/day.  The aPAD is 0.0034 mg/kg/day.  Dietary risk results >100% of the aPAD are above the Agency’s level of concern.  Refer to Table 3 above.

	Chronic PAD.  Combined dietary risk for triadimefon and triadimenol was assessed by comparing chronic dietary exposure estimates (in mg/kg/day) to the triadimefon cPAD.  Dietary risk is expressed as a percent of the cPAD, which is the chronic RfD (3.4 mg/kg/day-NOAEL) modified by an uncertainty factor of 1000 (10X for inter-species extrapolation, 10X for intra-species variability, and 10X FQPA safety factor for database uncertainty- lack of a developmental neurotoxicity study).  Therefore, the cPAD for triadimefon and triadimenol is 0.0034 mg/kg/day.  Dietary risk results >100% of the cPAD are above the Agency’s level of concern.    SEQ CHAPTER \h \r 1   SEQ CHAPTER \h \r 1 The cPAD was derived from a subchronic neurotoxicity study in rats, which accounted for the most sensitive species and endpoints (rat versus chronic dog study), with a LOAEL of 54.6 (male) and 68.7 (female) mg/kg/day as noted in Table 3 above.

			  TC "d.	Exposure Assumptions" \f C \l "4"    SEQ CHAPTER \h \r 1 a. Dietary (Food) Risk Assessment  TC "e.	Dietary (Food) Risk Assessment" \f C \l "4"

The Agency conducted acute and chronic dietary exposure assessments using the Dietary Exposure Evaluation Model software with the Food Commodity Intake Database (DEEM-FCID, Version 2.03), which incorporates consumption data from USDA’s Continuing Surveys of Food Intakes by Individuals (CSFII), 1994-1996 and 1998.

				1)	Acute Dietary Food Risk  TC "1)	Acute Dietary Risk" \f C \l "5"

A probabilistic (Monte-Carlo) acute dietary exposure assessment was conducted based on field trial data and 100% crop treated (%CT) at the 95th percentile.  The risk assessment combined exposure for both triadimefon and triadimenol.  Acute dietary (food only) risk estimates were based on field trial data for pineapples (triadimefon and triadimenol) and bananas (triadimenol), plus seed treatment uses on cotton and grain (barley, corn, oats, rye, sorghum, and wheat) from triadimenol based on a tolerance level approach and assuming 100% crop treated.  The ratio of total toxic residues (TTR) to triadimefon, from available metabolism studies, was used to estimate the total residues of concern.

For food alone, acute dietary risk estimates are below the Agency’s level of concern (<100% aPAD) at the 95th percentile exposure for children 1-2 years old at 32% of the aPAD, the most highly exposed population subgroup.  The 95th percentile of exposure is the appropriate percentile to use given the level of refinement (i.e., unrefined) of the residue values used and that 100% of the crops are assumed to be treated.  Refer to Table 5 below.

Table 5.  Results of Acute Dietary Exposure Analysis for Food Alone Using DEEM-FCID

Population Subgroup

aPAD (mg/kg/day)

95th Percentile

Exposure (mg/kg/day)

% aPAD

General U.S. Population	0.0034	0.000520	15

All Infants (< 1 year old)

0.0034

0.000828

24

Children 1-2 years old

0.0034

0.001083

32

Children 3-5 years old

0.0034

0.000923

27

Children 6-12 years old

0.0034

0.000668

20

				2)	Chronic Dietary Food Risk  TC "2)	Chronic Dietary Risk" \f C \l "5"

  SEQ CHAPTER \h \r 1

Chronic dietary exposure assessments were also conducted using the Dietary Exposure Evaluation Model software with the Food Commodity Intake Database (DEEM-FCID, Version 2.03), which incorporates consumption data from USDA’s Continuing Surveys of Food Intakes by Individuals (CSFII), 1994-1996 and 1998.

The risk assessment combined exposure for both triadimefon and triadimenol.  Chronic dietary (food only) risk estimates were based on field trial data for pineapples (triadimefon and triadimenol) and bananas (triadimenol), plus seed treatment uses on cotton and grain (barley, corn, oats, rye, sorghum, and wheat) from triadimenol using a tolerance level approach and assuming 100% crop treated.

For all supported commodities, the chronic dietary exposure to triadimefon from food (only) is below the Agency’s level of concern (<100% cPAD) for the U.S. population (6% cPAD) and all population subgroups, including children 1-2 years old (15% of the cPAD), the most highly exposed subgroup.  Refer to Table 6 below.

Table 6.  Results of Chronic Dietary Exposure Analysis for Food Alone Using DEEM-FCID

Population Subgroup

cPAD (mg/kg/day)

Food Alone

Exposure (mg/kg/day)

% cPAD

General U.S. Population

0.0034

0.000194	6

All Infants (< 1 year old)

0.0034

0.000227

7

Children 1-2 years old

0.0034

0.000493

15

Children 3-5 years old

0.0034

0.000471

14

Children 6-12 years old

0.0034

0.000323

10

			b.	Dietary Exposure from Drinking Water  TC "1.	Dietary Risk from Drinking Water" \f C \l "4"

Surface Water Exposure

  TC "a.	Surface Water" \f C \l "4"

Triadimefon and triadimenol can be transported to surface water during or after application via run-off and/or erosion as well as soil leaching from ground applications.  The triadimefon surface water assessment is based on Florida turf use.  This scenario was chosen because it is expected to present the greatest risk to drinking water supplies. Because water monitoring data for triadimefon are limited, the Agency used screening-level models to estimate drinking water concentrations of triadimefon from surface water.

Since current labels do not limit the number of applications, EECs were calculated for a range of numbers of applications for residential and golf/sod turf.  However, Bayer, the technical registrant, is only supporting a maximum turf rate of 2 applications of 2.7 lbs. ai/A for golf courses and sod farms.  As a result, only those results are presented here.  Since there is no limitation for application to tees, greens, and/or fairways, “entire course” values (also applies to sod farm use) were used in determining potential surface drinking water concentration(s).

A summary of the surface water concentration scenarios is presented below in Table 7.  For additional information, refer to the Tier 2 Drinking Water Assessment for Triadimefon and its Major Degradate Triadimenol, dated August 31, 2005.

Table 7.  Estimated Concentrations of Triadimefon and its Degradate Triadimenol in Surface Drinking Water Using PRZM/EXAMS Scenarios (Turf)

Use Scenario

Portion of Golf Course- (Treated)	Acute Concentration (ppb)

Chronic Concentration (ppb)

1 in 10 year annual mean (non-cancer) (ppb)	30-year overall mean (cancer)

(ppb)

2 applications

14 day interval

2.75 lbs ai/A

(1 oz/1000 ft2)

Entire Course	93.5

19.6

9.1

Groundwater Exposure

As an initial screen, the concentrations expected in ground water for the use of triadimefon were estimated using the SCI-GROW model (Tier 1 Ground Water Computer Model).  In addition, groundwater monitoring studies were supplied by the registrant, Bayer CropScience.  Although SciGrow should typically over-estimate expected ground water concentrations, in this case the model actually underestimated the SciGrow predicted value in at least one instance.  A ground water monitoring study in New Jersey, which reflected suggested turf uses, showed a peak groundwater concentration of 25 ppb, while the SciGrow estimate for similar usage yielded an estimate of only 3.36 ppb.  Therefore, the potential for ground water triadimefon contamination may be greater than supposed.  Although the ground water monitoring values were lower than surface water modeled values, there may be an unforeseen risk to private shallow ground water wells used for drinking water in areas where triadimefon is applied.  This may be further exacerbated by the fact that, unlike surface water, which is generally treated prior to use, private well water may be used in the home with no pre-treatment.  However, although the Agency recognizes the potential for groundwater contamination, surface water estimates in this case are considered protective for ground and/or drinking water contributions.  For more information on drinking water risks and representative calculations, see the Water Exposure/Risk Pathway section of the revised human health risk assessment, dated February 9, 2006.

		c.	Dietary Risk from Drinking Water

Drinking water exposure to pesticides can occur through ground and surface water contamination.  In assessing drinking water risks, EPA considers acute (one-day) and chronic (long-term) exposure, and uses modeling and monitoring data, if available, to estimate those exposures.  Given the limited use patterns of triadimenol (seed treatment) and the amount of pesticide available on a per acre basis, drinking water exposures resulting from the use of triadimefon in both surface and ground water are much greater.  Consequently, the Agency is using the exposure values from the use of triadimefon in its assessments which is protective of any drinking water exposure from the use of triadimenol.   Estimated environmental drinking water concentrations (EDWCs) for triadimefon were calculated using the PRZM-EXAMS model.  The assessment also accounted for triadimenol as the primary degradate in water.  The PRZM-EXAMS assessment considers 100% of the golf course was treated and that the watershed was 100% golf course.  Based on these conservative assumptions, the Agency is regulating at the 95 percentile.   The distribution of estimated residues of triadimefon and triadimenol were incorporated directly into the acute dietary assessment.

Triadimefon transforms into triadimenol in the natural environment, particularly in shallow subsurface soil and is moderately mobile and persistent.  Triadimefon on or near the soil surface or on vegetation may be subject to runoff and/or erosion into surface water bodies used as drinking water supplies.  Triadimefon and triadimenol may also leach into groundwater when triadimefon is applied in areas with well-drained soil, high rainfall (and/or irrigation) rates, and shallow water tables.  Once it reaches groundwater, triadimenol is likely to degrade more slowly than the parent compound.  Both parent and degradate are stable to hydrolysis and have fairly long half-lives in soil and water.  The Agency modeled surface drinking water values which are higher than groundwater estimates, and are therefore protective for dietary risk analyses.

			       1)	  Acute Dietary Water Risk

The Agency believes it is appropriate to use the 95th percentile as the level of concern (LOC) for drinking water because the drinking water assessment is conservative.  The following factors provide the rationale for this approach: 1) the Agency assumes that 100 percent of the watershed is in golf courses (100 percent cropped area (PCA)), and therefore 100% of the watershed is turf treated with triadimefon; 2) residue estimates were modeled using PRZM-EXAMS, which usually results in higher water concentration values than would monitoring data; 3) the dose spacing between the NOAEL and LOAEL in the guideline acute and subchronic neurotoxicity studies is fairly large; and 4) the entire golf course is assumed to be treated.

  Acute dietary (water only) risk estimates were based on a FL golf course scenario for triadimefon.  The acute dietary exposure to triadimefon from water (only) is below the Agency’s level of concern (<100% cPAD) for the U.S. population (24% aPAD) and all population subgroups, including all infants (< 1 year old) (85% of the aPAD), the most highly exposed subgroup (See Table 8).

Table 8. Results of Acute Dietary Exposure Analysis for Water (only) Using DEEM-FCID

Population Subgroup

aPAD (mg/kg/day)

95th Percentile

Exposure (mg/kg/day)

% aPAD

General U.S. Population

0.0034

0.000812	24

All Infants (< 1 year old)

0.0034

0.002904

85

Children 1-2 years old

0.0034

0.001235

36

Children 3-5 years old

0.0034

0.001148

34

Children 6-12 years old

0.0034

0.000789

23

2)	Chronic Dietary Water Risk

  Chronic dietary (water only) risk estimates were based on this scenario incorporating both triadimefon and its degradate triadimenol to determine risk values.  The chronic dietary exposure to triadimefon from water (only) is below the Agency’s level of concern (<100% cPAD) for the U.S. population (12% cPAD) and all population subgroups, including non-nursing infants (49% of the cPAD), the most highly exposed subgroup (See Table 9).

Table 9. Results of Chronic Dietary Exposure Analysis for Water (only) Using DEEM-FCID

Population Subgroup

cPAD (mg/kg/day)

95th Percentile

Exposure (mg/kg/day)

% cPAD

General U.S. Population

0.0034

0.000414	12

Infants (non-nursing)

0.0034

0.001681

49

Children 1-2 years old

0.0034

0.000615

18

Children 3-5 years old

0.0034

0.000575

17

Children 6-12 years old

0.0034

0.000397

12

		5.	Residential (Non-dietary) Exposure and Risk  TC "3.	Residential (Non-dietary) Risk" \f C \l "3"

Triadimefon

	The registrant has agreed to voluntarily delete residential turf use based on exposure to toddlers.

Triadimenol

	There are no residential uses of triadimenol products.

	Currently, triadimefon products are marketed for homeowner use on residential lawns, landscape ornamentals, and trees.  Triadimefon-containing products are also marketed for use by professional applicators (Pest Control Operators, or PCOs) on residential turf, on golf courses, other turf such as recreational/commercial areas, and on ornamental plantings.  Based on these uses, triadimefon is assessed for the residential handler, and for post-application dermal contact for adults, youths, and for toddler’s post-application incidental oral exposure that may occur from turf contact.  Residential exposure may occur during and after application at homes, or after applications at golf courses, parks, schools, or other turf sites.  Each route of exposure (oral, dermal, inhalation) is assessed, where appropriate, and risk is expressed as a Margin of Exposure (MOE > 1000 does not exceed the Agency’s Level of Concern).  For more information on residential exposure and risk, refer to the document, Triadimefon: Occupational and Residential Exposure Assessment for the Reregistration Eligibility Decision Document, dated June 30, 2006.

Residential Handler Risk

The anticipated use patterns and current labeling indicate several residential handler exposure scenarios based on the types of equipment and techniques that can be used to make triadimefon applications.  The quantitative short-term exposure/risk assessment developed for residential handlers is based on these scenarios.  Intermediate-or long-term exposures are not likely because of the intermittent nature of applications by homeowners.

(Mixer/Loader/Applicators):

(1) Liquid Formulations: Low Pressure Handwand (ORETF data for ornamentals)

	(2) Wettable Powder Formulations: Low Pressure Handwand (PHED data)

(3) Liquid Concentrates with Hose-End Sprayer (Residential ORETF data -- ornamental shrubs)

	(4) Wettable Powders with Hose-End Sprayer (Residential ORETF data -- liquid 	concentrate application to ornamentals)

	(5) Liquid Concentrates with a Tree Injector (no data)

	(6) Loading/Applying Granulars via Push Type Spreader (ORETF data)

	(7) Loading/Applying Granulars via Belly Grinder (PHED data)

Inhalation risks for residential handlers are not a concern for all residential uses of triadimefon.  Combined dermal and inhalation risks for residential handlers are not a concern (MOEs >1000) for the following scenarios:

(1) Mixing/loading/applying liquid and wettable powder formulations to outdoor and greenhouse flowers, trees, and shrubs with a low pressure handwand;

(2) Loading/applying granulars via push type spreader and belly grinder.

However, combined risks remain a concern (MOEs < 1000) for mixing/loading/applying liquid concentrates/ wettable powders with a hose-end sprayer to greenhouse ornamentals.  Short-term risks for residential handlers are presented below in Table 10, which only represents those scenarios that exceed the Agency’s level of concern (MOE < 1000).

Table 10.  Triadimefon Residential Handler Risks

Exposure Scenario

Crop or Target

App Ratea

(lb ai

/gallon)

Area Treated Dailyb

(gallons)

Baseline Unit Exposure

MOEs

Dermalc

(mg/lb ai)

Inhalationd  (mg/lb ai)

Baseline Dermal

Baseline Inhalation

Baseline Dermal +

Baseline Inhalation MOE

Mixer/Loader/Applicator

Mixing/

Loading/

Applying Liquid Concentrates with Hose-End Sprayer	Greenhouse ornamentals (shrubs, trees)	0.00938	100	39	1.6	490	160000	490

Mixing/

Loading/

Applying Liquid Concentrates with Hose-End Sprayer	Greenhouse

ornamentals (flowering)	0.00938	100	34	0.82	560	310000	560

Mixing/

Loading/

Applying Wettable Powders with Hose-End Sprayer	Greenhouse

ornamentals (flowering)	0.00625	100	34	0.82	850	460000	850

a  Application rates are the maximum application rates determined from EPA registered labels for triadimefon.

b  Amount handled per day values are EPA estimates of acres, square feet, or cubic feet treated or gallons applied based on Exposure SAC, SOP #9 Standard Values for Daily Acres Treated in Agriculture, and industry sources, and EPA estimates.

c Baseline Dermal:  Long-sleeve shirt, long pants, no gloves.

d Baseline Inhalation: no respirator.

				b.	Residential Post-application Exposure and Risks

The Agency uses the term “post-application” to describe exposures to individuals that occur as a result of being in an environment that has been previously treated with a pesticide.  Triadimefon can be used in many areas that can be frequented by the general population including residential areas (e.g., home lawns and gardens).  As a result, individuals can be exposed by entering these areas if they have been previously treated.

Exposures were calculated by considering the potential sources of exposure (e.g., dislodgeable foliar residues (DFRs) on ornamental plants) for both triadimefon and triadimenol, then calculating dermal and non-dietary ingestion exposures and risks.  Individuals of varying ages can potentially be exposed to triadimefon when they are in areas that have been previously treated.  Post-application exposure scenarios were developed for each residential setting where triadimefon can be used.  The scenarios that were assessed are dermal exposure to adults, dermal exposure to youths, and dermal and incidental oral exposure to toddlers from those uses which remain where there is a potential for post-application exposure.

	Risk Summary:

Risks were calculated using the Margin of Exposure (MOE) approach, which is a ratio of the body burden to the toxicological endpoint of concern.  Risks to adults and youths are below the Agency’s level of concern (See Table 11 & 12 below).

Table 11.  Adult Residential Risk Estimates for Post-application Exposure to Triadimefon (including Triadimenol)

Exposure Scenario	Route of Exposure	Formulation	Application Rate

(lb ai/acre)	MOE at Day 0

Outdoors – with default transferable residues

Home Garden (Ornamentals)	Dermal	Spray	0.25	4,800

Golfer	Dermal	Spray/Granular	1.3 (Bayer max residential)	12,000

Table 12. Youth Residential Risk Estimates for Post-application Exposure to Triadimefon (including Triadimenol)

Exposure Scenario	Route of Exposure	Formulation	Application Rate

(lb ai/acre)	MOE at Day 0

Outdoors – with default transferable residues

Home Garden (Ornamentals)	Dermal	Spray/Granular	0.25	13,000

Golfer	Dermal	Spray/Granular	1.3 (Bayer max residential)	7,800

The registrant has agreed to voluntarily cancel all residential turf use and include a pre-transplant interval of 17 days to sod farms in order to address any potential concerns for post-application exposure to toddlers.

Additional details regarding the residential exposure and risk assessments for triadimefon may be found in the following documents:  Triadimefon. Occupational and Residential Exposure Assessment for the Reregistration Eligibility Decision Document, dated June 30, 2006.

		6.	Aggregate Exposure/Risk from Triadimefon and Triadimenol

The FQPA amendments to the FFDCA, section 408(b)(2)(A)(ii)) require the Agency to determine “that there is a reasonable certainty that no harm will result from aggregate exposure to the pesticide chemical residue, including all anticipated dietary exposures and other exposures for which there is reliable information.”  Aggregate exposure will typically include exposures from food, drinking water, residential uses of a pesticide, and other non-occupational sources of exposure.  When aggregating exposure and risk from various sources, the Agency considers the route and duration of exposure.

Acute (Food and Water)

	The Agency believes it is appropriate to use the 95th percentile as the level of concern (LOC) for the entire golf course because it is a highly conservative approach.  The following factors provide the rationale for this approach: 1) the Agency assumes that 100 percent of the watershed is in golf courses (100 percent cropped area (PCA)), and therefore 100% of the watershed is turf treated with triadimefon; 2) residue estimates were modeled using PRZM-EXAMS, which usually results in higher water concentration values than would monitoring data; 3) the dose spacing between the NOAEL and LOAEL in the guideline acute and subchronic neurotoxicity studies for triadimefon are fairly large; and 4) the Agency assumes that the entire golf course is treated.

	Combined acute dietary (food and water) risk estimates from pineapples (triadimefon) and drinking water (triadimefon from golf course application to entire golf course) plus seed treatment uses and banana import tolerance (triadimenol) are below the Agency’s level of concern (<100% aPAD) at the 95th percentile of exposure (assuming 2 applications per year for turf at 2.7 lbs ai/A).  The dietary exposure for acute food and drinking water is 33% of the aPAD for the U.S. population and 94% of the aPAD for all infants less than one year old, the most highly exposed population subgroup.  A summary of acute dietary risk estimates (food + drinking water) is presented below in Table 13.

Table 13.  Triadimefon and Triadimenol Results of Acute Dietary Exposure Analysis for Food + Drinking Water From the Golf Course (entire) Use Scenario Using DEEM-FCID

Population Subgroup

aPAD (mg/kg/day)

95th Percentile

Exposure (mg/kg/day)

% aPAD

General U.S. Population

0.0034

0.001106	33

All Infants (< 1 year old)

0.0034

0.003190

94

Children 1-2 years old

0.0034

0.001959	58

Children 3-5 years old

0.0034

0.001765

52

Children 6-12 years old

0.0034

0.001210

36

Chronic (Food and Water)

	Combined chronic dietary (food and water) risk estimates were derived from pineapples and drinking water (entire golf course-triadimefon) plus seed treatment uses and bananas import tolerance from triadimenol.  Drinking water exposures are based on using the 1 in 10 year annual mean concentration assuming 2 applications per year for turf at 2.7 lbs ai/A.  The dietary exposure for chronic food and drinking water is below the Agency’s level of concern and is 18% of the cPAD for the U.S. population and 57% of the cPAD for non-nursing infants, the most highly exposed population subgroup.  A summary of chronic dietary risk estimates (food + drinking water) is presented below in Table 14.

Table 14.  Triadimefon Results of Chronic Dietary Exposure Analysis for Food + Drinking Water From the Golf Course (entire) Using DEEM-FCID

Population Subgroup

cPAD (mg/kg/day)

95th Percentile

Exposure (mg/kg/day)

% cPAD

General U.S. Population

0.0034

0.000607	18

Infants (non-nursing)

0.0034

0.001952

57

Children 1-2 years old

0.0034

0.001108	33

Children 3-5 years old

0.0034

0.001047

31

Children 6-12 years old

0.0034

0.000720

21

Short-term (Food + Water + Residential)

	The exposure attributable to residential uses of triadimefon were not initially aggregated with dietary sources of exposure (food plus drinking water) because at that time the dietary and residential exposure pathways separately exceeded the Agency’s level of concern.  The registrant agreed to voluntarily delete residential turf uses and all food uses (except pineapple) so that the aggregate risks are within acceptable levels.  Taking into consideration the agreement to request deletion of these uses and mitigation requiring a 17-day post-application, pre-transplant interval for sod farms, risks will be below the Agency’s level of concern.

	Aggregate exposures to toddlers, youths, and adults could occur from triadimefon uses on golf courses and in residential settings from turf transplanted from sod farms.  The Agency assessed short-term aggregate risks to adults and toddlers by calculating an aggregate risk MOE assuming background (chronic) exposure to triadimefon and triadimenol residues from dietary (food and water) sources.  The chronic exposure from drinking water considers treatment of an entire golf course.  Short-term aggregate risk, calculated as an MOE, is 1100 for toddlers (from the turf use), and 1300 for adults and for youths (from the golf course use).  None of these estimates exceed the Agency’s level of concern.

	Aggregate exposures could also occur for adults making applications to residential ornamentals.  Using this scenario and assuming an application rate of 0.005 to 0.0025 lb. ai/gallon with the highest exposure scenario that is still below the Agency’s level of concern (mixing/loading/applying wettable powders with a low pressure handwand to greenhouse ornamentals), aggregate (food + water + residential) risk is below the Agency’s level of concern (MOE = 1300).

	The combined risk assessment for exposures to toddlers following the application of sod farm turf transplanted to a residential lawn are not a concern (MOEs > 1000) at day 17 following application to sod farms at the 2.7 lbs ai/A rate.  Therefore, the labels for these products must be restricted to not allow transplantation earlier than the 17th day after treatment.

Intermediate-term and Chronic (Food + Water + Residential)

	Intermediate-term and chronic residential exposures to triadimefon are not expected because of the intermittent nature of applications in residential settings.  Therefore, intermediate-term chronic aggregate risk assessments were not conducted.

	7.	Pesticide and Pharmaceutical Co-Exposure Assessment for

The Triazole Metabolites

FFDCA Section 408 requires EPA to consider potential sources of exposure to a pesticide and related substances in addition to the dietary sources expected to result from a pesticide use subject to a tolerance (legal limit for pesticide residue levels) in food or feed commodities.  In determining whether to maintain a pesticide tolerance, EPA must “determine that there is a reasonable certainty of no harm…” in accordance with FFDCA, Section 408(b)(2)(A)(ii).  The FDA regulates human drugs for safety and effectiveness under FFDCA section 505 and may approve use of a drug in humans notwithstanding the possibility that some individual patients may experience adverse side effects.  EPA does not believe that, for purposes of the section 408 dietary risk assessment, it is compelled to treat a pharmaceutical patient the same as a non-patient, or to assume that combined exposures to pesticide and pharmaceutical residues that lead to a physiological effect in the patient constitutes “harm” under the meaning of section 408 of the FFDCA.

Rather, EPA believes that an appropriate way to consider the metabolite 1,2,4-triazole resulting from pharmaceutical use of triazole-derivative drugs would be to consider the additional contribution that non-occupational pesticide exposure would have to a pharmaceutical patient exposed to the same compound.  Where the additional pesticide exposure has no more than a minimal impact on the pharmaceutical patient, EPA can make a “reasonable certainty of no harm” finding for the pesticide tolerances of that compound under FFDCA Section 408.  If the potential impact on the pharmaceutical user as a result of co-exposure from pesticide use is more than minimal, then EPA would not be able to conclude that dietary residues were safe, and would need to discuss with FDA appropriate measures to reduce exposure from one or both sources.

As previously mentioned, triadimefon may share a common metabolite, 1,2,4-triazole, with triazole-derivative pharmaceutical compounds.  Thus, EPA consulted with FDA on triazole drugs that could metabolize to 1,2,4-triazole and the Agencies concluded that only one compound, anastrozole, a chemotherapy drug used to treat breast cancer, had this metabolic pathway in humans.  Because anastrozole is used at very small doses in a limited population of patients, EPA conducted a conservative screening-level assessment to determine whether the combined metabolites from triazole pesticide uses and anastrozole would adversely impact pharmaceutical users.  EPA concluded that, using upper-bound estimates for metabolites of anastrozole, the combined metabolite exposure is below the Agency’s level of concern.  Because EPA is able to reach this conclusion with a screening-level assessment, the Agency has not conducted a more refined co-exposure assessment for pharmaceutical uses as described above.  Therefore, EPA concludes that the potential dietary pesticide exposure to triazole pesticide residues in food and water will result in no harm to a patient being treated with anastrozole.  Please see the May 19, 2006, memo from FDA and the July 18, 2006, EPA document summarizing EPA and FDA discussions on potential free triazole metabolites of triazole derivative drugs, (both available in the public docket for triadimefon, EPA-HQ-OPP-2005-0258) for additional information.

  	 	8.	Cumulative Risk Assessment  TC "5.	Cumulative Risk Assessment" \f C \l "3"

  SEQ CHAPTER \h \r 1 Section 408(b)(2)(D)(v) of the FFDCA requires that, when considering whether to establish, modify, or revoke a tolerance, the Agency consider “available information” concerning the cumulative effects of a particular pesticide’s residues and “other substances that have a common mechanism of toxicity.”  Other substances are considered to account for the possibility that low-level exposures to multiple chemical substances that cause a common effect by a common mechanism could lead to the same adverse health effect as would a higher level of exposure to each individual substance.  For the purposes of this reregistration eligibility decision, EPA has concluded that triadimefon and triadimenol do not share a common mechanism of toxicity with other substances.  The Agency reached this conclusion after a thorough internal review and external review of the data supporting a common mechanism of toxicity for a number of chemical classes.  Triadimefon, triadimenol, and the other triazole fungicides share the common metabolites 1,2,4-triazole, triazole alanine, and triazole acetic acid, which are considered in this RED.

		9.	Occupational Risk  TC "6.	Occupational Risk" \f C \l "3"

The registrant has agreed to voluntarily delete all uses on apples, pears, grapes, raspberries, and residential turf.  Occupational post-application exposure and risk assessment for agricultural uses of triadimefon indicates that risks are not a concern at day 0 (i.e., 12 hours after application) for all use sites and all post-application activities.

  SEQ CHAPTER \h \r 1 Workers can be exposed to a pesticide through various routes/pathways.  There is potential for exposure to triadimefon in occupational scenarios from handling triadimefon products during the application process (i.e., mixer/loaders, applicators, flaggers, and mixer/loader/applicators), and a potential for post-application worker exposure from entering into areas previously treated with triadimefon.  In addition, there is potential exposure to workers who treat seed with triadimefon in commercial and nursery settings and to persons who plant treated seed.  Occupational risk for all of these potentially exposed populations is measured by a MOE, which determines how close the occupational exposure comes to a dose level or NOAEL.

Occupational risk is assessed for exposure at the time of application (termed “handler” exposure) and following application (termed post-application exposure).  Application parameters are generally defined by the physical nature of the formulation (e.g., formula and packaging), by the equipment required to deliver the chemical to the use site, and by the application rate required to achieve an efficacious dose.  Post-application risk is assessed for activities such as scouting, irrigating, pruning, and harvesting, and is based primarily on dermal exposure estimates.  Note that occupational risk estimates are intended to represent pesticide workers, and on this basis assumptions are made concerning acres treated per day and the seasonal duration of exposure.

Triadimenol is only being reviewed for tolerance reassessment purposes.  Currently registered uses do not involve occupational exposures.  Therefore, no worker risk assessment was completed.

For more information on the assumptions and calculations of potential risk of triadimefon to workers, refer to the documents entitled: Triadimefon. Occupational and Residential Exposure Assessment for the Reregistration Eligibility Decision Document, dated June 30, 2006; and the memorandum: Triadimefon/Triadimenol: Summary of Refinements and Revisions to the Human Health Risk Assessment, dated July 10, 2006.

			a.	Occupational Toxicity  TC "a.	Occupational Toxicity" \f C \l "4"

  SEQ CHAPTER \h \r 1 Table 15 below provides a listing of the toxicological endpoints used in the triadimefon occupational risk assessment.

Table 15.  Toxicological Endpoints for the Triadimefon Occupational Risk Assessment

Exposure

Scenario

Dose Used in Risk Assessment, UF

Level of Concern for Risk Assessment

Study and Toxicological Effects

Dermal

Short-Term

(1 - 30 days)	Dermal NOAEL = 300 mg/kg/day

   UF = 100

Occupational

MOE = 100	21 day dermal toxicity in rabbits.

The LOAEL= 1000 mg/kg/day based on increased reactivity and activity in the females.

Dermal

Intermediate-Term

(1 - 6 months)	Dermal NOAEL = 300 mg/kg/day

   UF = 100

Occupational

MOE = 100

21 day dermal toxicity in rabbits.

The LOAEL= 1000 mg/kg/day based on increased reactivity and activity in the females.

Inhalation

Short-Term

(1 - 30 days)

NOAEL = 3.4 mg/kg/day

(Inhalation absorption rate = 100%)

   UF = 100

Occupational

MOE = 100	Subchronic neurotoxicity study in rats.

LOAEL = 54.6/68.7 mg/kg/day based largely on hyperactivity.

Inhalation

Intermediate-Term

(1 - 6 months)

NOAEL = 3.4 mg/ kg/day

(Inhalation absorption rate = 100%)

   UF = 100

Occupational

MOE = 100	Subchronic neurotoxicity study in rats.

LOAEL = 54.6/68.7 mg/kg/day based largely on hyperactivity.

Cancer (oral, dermal, inhalation)

Classification: Category C (possible human carcinogen) based on statistically significant increase in thyroid adenomas in male Wistar rats and statistically significant increases in hepatocellular adenomas in both sexes of the NMRI mouse.

			b.	Occupational Handler Exposure  TC "b.	Occupational Handler Exposure" \f C \l "4"

  SEQ CHAPTER \h \r 1 Occupational handler risk estimates have been assessed for both short- and intermediate-term exposure durations.  Due to the use patterns for triadimefon, long-term exposures are not expected.  Since the endpoints and points of departure (PODs) are identical to assess short and intermediate exposure, these risk estimates represent both durations of exposure.

Occupational handler assessments are conducted using increasing levels of protection.  The Agency typically evaluates all exposures with minimal protection and then considers additional protective measures using a tiered approach in an attempt to obtain an adequate MOE.  The lowest tier is represented by the baseline clothing scenario (i.e., single layer clothing, socks, and shoes), followed by increasing levels of risk mitigation such as personal protective equipment (PPE) and engineering controls (EC).  In the case of triadimefon, exposure to pesticide handlers is likely during the occupational use of the pesticide in a variety of occupational environments.  The anticipated use patterns and current labeling indicate several occupational exposure scenarios based on the types of equipment and techniques that can potentially be used for triadimefon applications. Based on the use patterns, twenty-seven major occupational handler exposure scenarios (non-seed treatment) were identified.  In addition, six major exposure scenarios were identified for pine seed treatment.  The following exposure scenarios were used to develop the risk assessment for occupational handlers.

(Non-seed treatment)

	Mixer/Loaders:

	(1a) Liquid Formulations to support Aerial Applications (PHED)

	(1b) Liquid Formulations to support Groundboom Applications (PHED)

	(1c) Liquid Formulations to support LCO Handgun Applications (PHED)

	(1d) Liquid Formulations to support Airblast Applications (PHED)

	(2a) Wettable Powders to support Aerial Applications (PHED)

	(2b) Wettable Powders to support Chemigation Applications (PHED)

	(2c) Wettable Powders to support Groundboom Applications (PHED)

	(2d) Wettable Powders to support LCO Handgun Applications (PHED)

	(2e) Wettable Powders to support Airblast Applications (PHED)

	(2f) Wettable Powders to support Rights-of-Way Applications (PHED)

	(3a) Water Dispersible Granules to support Aerial Applications (PHED)

	(3b) Water Dispersible Granules to support Chemigation Applications (PHED)

	(3c) Water Dispersible Granules to support Groundboom Applications (PHED)

	(3d) Water Dispersible Granules to support LCO Handgun Applications (PHED)

	(4a) Loading Granulars to support Aerial Applications (PHED)

	(4b) Loading Granulars to support Tractor Drawn Spreader Applications (PHED)

	Applicators:

	(5) Aerial Spray Applications (PHED)

	(6) Aerial Granular Applications (PHED)

	(7) Groundboom Spray Applications (PHED)

	(8) Airblast Spray Applications (PHED)

	(9) Handgun Spray Applications (PHED)

	(10) Rights of Way Spray Applications (PHED)

	(11) Tractor-Drawn Spreader Granule Applications (PHED)

	Flaggers:

	(12) Flagging for Aerial Spray Applications (PHED)

	(13) Flagging for Aerial Granular Applications (PHED)

	Mixer/Loader/Applicators:

	(14) Liquid Formulations: Low Pressure Handwand Sprayer (ORETF)

	(15) Wettable Powder Formulations: Low Pressure Handwand Sprayer (PHED)

(16) Water Dispersible Granules with Low Pressure Handwand (using ORETF data for liquid formulations as a surrogate)

	(17) Liquid Formulations: Handgun Sprayer (ORETF)

	(18) Wettable Powders with a Handgun Sprayer (ORETF)

	(19) Water Soluble Bags with Handgun Sprayer (ORETF)

	(20) Dry Flowables Concentrates with a Handgun Sprayer (ORETF)

	(21)  Liquid Formulations: High Pressure Sprayer (PHED)

	(22) Water Dispersible Granules: High Pressure Handwand (PHED: liquid  concentrates)

	(23) Wettable Powders: High Pressure Handwand (PHED: liquid concentrates)

	(24) Liquids with an Tree Injector (no data)

	(25) RTU: Briquette (no data)

	(26) Liquid Formulations: Dip (no data)

(27) Loading/Applying Granulars via Push Type Spreader (ORETF)

	(Pine seed treatment)

(S-1) on-nursery loading/applying with hopper or planter box seed treatment,

(S-2) on-nursery loading/planting previously treated seeds,

(S-3) on-nursery loading/applying wettable powders using cement mixer equipment (using PHED mixing/loading WP data),

(S-4) on-nursery loading/applying dry flowables using cement mixer equipment (using PHED mixing/loading DF data),

	(S-5) on-nursery drying/raking/bagging treated seed,

(S-6) loading and applying wettable powder formulations with commercial seed-treatment equipment,

(S-7) commercial sewer stitching bags of seed,

(S-8) bagging and otherwise handling treated seeds with commercial equipment, and

(S-9) multiple commercial seed treatment activities.

			c.	Occupational Handler Risk Summary  TC "c.	Occupational Handler Risk Summary" \f C \l "4"

  SEQ CHAPTER \h \r 1 The Agency has determined that there are potential exposures to individuals who mix, load, apply, and otherwise handle triadimefon during the usual use patterns associated with the pesticide’s use.

In all non-seed treatment scenarios, combined dermal and inhalation MOEs meet or exceed the level of concern of 100 at some level of risk mitigation (personal protective equipment or engineering controls).  In the majority of scenarios where data are available, combined dermal and inhalation risks are not a concern at baseline (long-sleeve shirt, long pants, shoes, socks, no respirator) or baseline plus chemical-resistant gloves.  However, there are risk concerns requiring additional dermal or inhalation protection (e.g. a respirator or engineering controls) for several of the scenarios involving mixing/loading/applying wettable powder (See Table 16).

	In all the in-nursery seed treatment scenarios where data are available, combined dermal and inhalation MOEs meet or exceed the required level of concern of 100 at baseline or baseline plus chemical-resistant gloves.  For commercial seed treatment, combined dermal and inhalation risks meet or exceed the required MOE of 100 with baseline PPE.

Table 16.  Combined Dermal plus Inhalation Handler Risks for Agricultural and Commercial Uses

Exposure Scenario	Crop or Target	App Rate (lb ai/acre)a	Area Treated Daily (acre)b	Combined MOEsi

Baselinec Dermal + Baseline Inh	Single layer w/

glovesd Dermal + Baseline Inh	Double layer w/ glovese Dermal + Baseline Inh	Single layer w/gloves  Dermal + 80% Rf Inh	Single layer w/ gloves Dermal + 90% Rg Inh	Double layer w/ gloves Dermal + 80% R Inh	Double layer w/ gloves Dermal + 90% R Inh	Eng Controlh Dermal + Inh

Mixer/Loader

Mixing/Loading Liquid Concentrates for Injection	ornamentals (shade trees, woody shrubs)	0.000026 lb ai/inch of trunk	inch of trunk	No Data  No Data 	No Data 	No Data 	No Data 	No Data 	No Data 	No Data

Mixing/Loading Wettable Powders for Aerial Applications	 Christmas trees 0.25	350	30	60	61	250

	turf (sod farm)	2.7 (except CA)	350	2.7 	5.6	5.6	23	38	24	42	680

	pine seedlings	0.5	350	15	30	30	130

Mixing/Loading Wettable Powders for Chemigation Applications	turf (sod farm)	2.7 (except CA)	350	2.7	5.6	5.6	23	38	24	42	680

Mixing/Loading Wettable Powders for

Groundboom Applications	azaleas	0.005 lb ai/gallon	16000

gallons	32	66	67	270

	turf (sod farm)	2.7	80	12	24	25	100

	turf (golf course)	2.7	40	24	49	49	200

Mixing/Loading Wettable Powders to Support Rights-of-way sprayer	turf (golf course and sod farms)	2.7	80	12	24	25	100

Applicator

Applying Sprays via Aerial Equipment	Christmas trees	0.25	350	No Data	No Data 	No Data 	No Data 	No Data 	No Data 	No Data 	20000

	turf (sod farm)	2.7	350	No Data	No Data 	No Data 	No Data 	No Data 	No Data 	No Data 	1900

	pine seedlings	0.5	350	No Data	No Data 	No Data 	No Data 	No Data 	No Data 	No Data 	10000

Applying Granulars via Aerial Equipment	turf (sod farm)	2.6	350	No Data No Data 	No Data 	No Data 	No Data 	No Data 	No Data 	200

Mixer/Loader/Applicator

Mixing/Loading/Applying Wettable Powders with Low Pressure Handwand (PHED)	turf (golf course, sod farms)	2.7	5	No Data 	15	15	53	79	58	92 Not Feasible

	pine seedlings	0.5	5	No Data 	78	81	290

Not Feasible

Mixing/Loading/Applying Liquids with an Injector	ornamentals (shade trees, woody shrubs)	0.000075 lb ai/1 inch of trunk circumference	inch of trunk circumference	No Data	No Data 	No Data 	No Data 	No Data 	No Data 	No Data 	Not Feasible

Mixing/Loading/Applying RTU Briquette	pine seedlings	0.00019 lb ai/seedling	seedlings	No Data	No Data 	No Data 	No Data 	No Data 	No Data 	No Data 	Not Feasible

Mixing/Loading/Applying Dip	pine seed (nurseries)	0.0000625 lb ai/gallon 100 gallons	No Data	No Data	No Data	No Data	No Data	No Data 	No Data 	No Data

	pineapple (post-harvest)	0.0028 lb ai/gallon	100 gallons	No Data	No Data	No Data	No Data	No Data	No Data 	No Data 	No Data

a	Application rates are the maximum application rates determined from EPA registered labels for triadimefon.

b	Amount handled per day values are HED estimates of acres treated per day based on Exposure SAC SOP #9 “Standard Values for Daily Acres Treated in Agriculture,” industry sources, and HED estimates.

c	Baseline = No gloves and no respirator (i.e., long sleeve shirt, long pants, shoes and socks.

d	Single layer w/gloves  is baseline attire plus chemical-resistant gloves.

e	Double layer w/gloves is coveralls worn over long-sleeve shirt and long pants, plus chemical-resistant gloves (with headgear).

f	80% Respirator is quarter-face dust/mist respirator (that provides an 80% protection factor).

g	90% Respirator is half-face dust/mist respirator (that provides a 90% protection factor).

h	Engineering control is closed mixing/loading system, enclosed cab, or enclosed cockpit.

i	Combined MOEs =1/[(1/Dermal MOE) + (/Inhalation MOE)]As noted above, there are no available data to assess the following: 1) mixing/loading/ applying liquids with a tree injector to ornamental trees and woody shrubs; 2) mixing/loading/applying dips to pineapples (pre-plant and post-harvest) and pine seed (nursery applications); 3) drying/raking/bagging treated pine seed; and 4) ready-to-use (RTU) briquette applications to pine seedlings.  Therefore, the Agency is requiring the use of gloves to mitigate potential dermal exposure for these uses described above.

			d.	Occupational Post-application Risk Summary  TC "d.	Occupational Postapplication Risk Summary" \f C \l "4"

  SEQ CHAPTER \h \r 1 Triadimefon is currently labeled for use on grapes, turf (including residential, golf course and sod farm turf), ornamentals, apples, pears, Christmas trees, pine seedlings, and raspberries.  Because of the use pattern, a wide array of individuals can potentially be exposed by working in areas that have been previously treated.  However, the registrant has agreed to voluntarily delete all uses on apples, pears, grapes, raspberries, and residential turf.  SEQ CHAPTER \h \r 1

The Agency has used the most up-to-date information available to complete the post-application risk assessment for triadimefon.  Several data gaps exist, such as a lack of triadimefon-specific post-application studies and lack of transfer coefficients for certain crop activities.  However, the existing database is adequate to assess post-application risk.

Occupational risks were calculated using a MOE, which is a ratio of the daily dose to the toxicological endpoint of concern.  Post-application risks diminish over time because triadimefon residues eventually dissipate in the environment.  Therefore, risks were calculated over time based on changing residue levels.  Occupational post-application exposure and risk assessment for agricultural uses of triadimefon indicates that risks are not a concern at day 0 (i.e., 12 hours after application) for all use sites and all post-application activities.  MOEs for occupational post-application risk range from 220 for transplanting, weeding (hand), harvesting (hand), and harvesting (mechanical) at the 2.7 lbs. ai/A rate on sod farms and golf course turf.

		10.	Human Incident Data

	  SEQ CHAPTER \h \r 1 In evaluating incidents to humans, the Agency reviewed reports from the National Poison Control Centers (PCC), California Department of Pesticide Regulation (CDPR), the Agency’s Office of Pesticide Program’s Incident Data System (IDS), the National Pesticide Information Center (NPIC), the National Institute of Occupational Safety and Health’s Sentinel Event Notification System for Occupational Risks (NIOSH SENSOR) for poisoning incident data on triadimefon/triadimenol.

	Data provided by the PCC reported nine incidents of occupational exposure to triadimefon and 46 non-occupational exposures from 1993 through 2003.  Of the 46 non-occupational exposures, 13 occurred in children under six years of age.  Of the total 20 cases with medically determined outcome, 11 reported minor medical outcome.  From a total of 55 exposures to triadimefon, just four were seen in a health care facility and none required hospitalization.  A review of symptoms revealed almost exclusively irritation effects (including rash and erythema) to skin, mouth, throat, and eyes.  In addition, there were four cases reporting headache and two reported cough.  No other significant symptoms were reported.

	The majority of triadimefon incidents (92%) reported by CDPR occurred prior to 1990.  Most of the triadimefon cases (73%) involved use on grapes which is a labor intensive crop involving high exposure to foliar residues.  Foliar residues accounted for half of the illnesses and nearly half of the systemic illnesses.  Skin, eye irritation, and rash were among the most common topical symptoms.  The most common systemic effects included nausea, headache, sneezing, congestion, difficulty breathing and other allergic-type reactions.  In addition, there were three reports of vomiting.  Furthermore, the registrant has voluntarily agreed to delete all food (apples, grapes, pears, and raspberries) uses.

	Reports submitted to the IDS indicate incidents from various sources.  The NPIC is a toll-free information service supported by OPP.  A ranking of the top 200 active ingredients for which telephone calls were received during calendar years 1984-1991, inclusive has been prepared.  The total number of calls was tabulated for the categories human incidents, animal incidents, calls for information, and others.  Triadimefon was not reported on the list of the top 200 chemicals with incidents reported to NPIC.  Triadimefon was associated with one case out of a total of 5,899 cases reported to NIOSH SENSOR between 1998 and 2003.  However, this case was a duplicate of a CDPR case, which had already been reported.

	Conclusion: Both California and Poison Control Center data show a pattern of irritative, but usually minor, symptoms from exposure to triadimefon.  Irritation to skin, eyes, and respiratory passage occur readily among unprotected handlers (applicators and mixer/loaders) and among those who have substantial contact with foliage such as grape harvesters and tenders.  Additionally, it should be noted that triadimefon is a skin sensitizer, and as such, may contribute to allergic-type reactions.  Furthermore, the registrant has voluntarily agreed to delete all uses on apples, grapes, pears, and raspberries.

B.	Environmental Fate and Effects Risk Assessment  TC "B.	Environmental Risk Assessment" \f C \l "2"

Triadimefon has the following registered uses, which result in environmental exposures: applications to fruits (apples, grapes, pears, and raspberries) turf, pine seedlings, Christmas trees, and ornamentals.  However, the registrant has agreed to voluntarily delete all use on apples, grapes, pears, raspberries, and residential turf.  SEQ CHAPTER \h \r 1   A summary of the Agency’s environmental risk assessment for triadimefon is presented below.  More detailed information associated with the environmental risk from the use of triadimefon can be found in the   SEQ CHAPTER \h \r 1 Environmental Fate and Ecological Risk Assessment (Revised) for Triadimefon, dated January 19, 2006 and Response to Bayer Public Comments Regarding the Environmental Fate and Effects Division Triadimefon Risk Assessment, dated June 1, 2006.  These documents may be accessed in the OPP Public Docket (docket number EPA-HQ-OPP-2005-0258) at   HYPERLINK "http://www.regulations.gov"  http://www.regulations.gov .

		1.	Environmental Fate and Transport  TC "a.	Environmental Fate and Transport" \f C \l "4"

Triadimefon is stable to hydrolysis but degrades by photolysis in water with a half-life of 7.6 hours.  In aerobic sandy loam soil, parent triadimefon degraded with a half life of 5.6 days, and in anaerobic sandy loam soil the half life was 23.1 days.  In anaerobic aquatic environments, triadimefon had a half-life of 217 days.  The primary degradate identified in environmental fate studies (aerobic/anaerobic soil and anaerobic aquatic) was triadimenol.  The other degradates identified in these studies were: p-chlorophenol (photolysis water/soil), 4-chlorophenoxy-1,2,4-triazol-1-yl-methane (aerobic soil), and 1H-1,2,4-triazole (aerobic soil).

The environmental fate assessment was based on an evaluation of total triadimefon toxic residues, which includes both parent and the degradate triadimenol.  Since approximately 75% of parent triadimefon degraded to triadimenol within 60 days post-application, for the purpose of modeling, physical characteristics that reflected combined properties of both compounds in proper relative proportions were used.  Thus, for example, the aerobic soil half-life for total residues used in modeling was 240 days.

Both triadimefon and triadimenol were shown to be moderately soluble, and are therefore capable of being transported dissolved in water as surface runoff or as leachate to groundwater.  The adsorption coefficients (Koc) for triadimefon and triadimenol were 387 L/kgoc and 365 L/kgoc (average of four soils), respectively.  Triadimenol appears to be even more prone to leaching than triadimefon.  This may be due partly to its formation in the aerobic subsurface, where subsequent rain or irrigation events can leach it deeper into the soil.  However, due to its moderate mobility and adsorption characteristics, triadimefon is capable of persisting and accumulating in a variety of environmental conditions.  Therefore, triadimefon is likely to be of greater concern for surface water runoff issues, but triadimenol is of greater concern for groundwater and apt to be more persistent than parent triadimefon in most settings.

	2.	Ecological Exposure and Risk  TC "b.	Aquatic Organism Exposure" \f C \l "4"

	To estimate potential ecological risk, EPA integrates the results of exposure and ecotoxicity studies using the risk quotient method.  Risk quotients (RQs) are calculated by dividing estimated environmental concentrations (EECs), based on environmental fate characteristics and pesticide use data, by ecotoxicity values for various wildlife and plant species.  RQs are then compared to levels of concern (LOCs), and when the RQ exceeds the level of concern for a particular category, the Agency presumes a risk of concern to that category.   See Table 17 for the Agency’s LOCs.  Risk characterization provides further information on potential adverse effects and the possible impact of those effects by considering the fate of the chemical and its degradates in the environment, organisms potentially at risk, and the nature of the effects observed.  To the extent feasible, the Agency seeks to reduce environmental concentrations in an effort to reduce the potential for adverse effects to non-target organisms.

Table 17.  EPA’s Levels of Concern and Associated Risk Presumptions

  SEQ CHAPTER \h \r 1 Risk Presumption	LOC

Terrestrial Animals	LOC

Aquatic Animals	LOC

Plants (Terrestrial/ Aquatic/Semi-Aquatic)

Acute Risk - there is potential for acute risk.	0.5	0.5	1

Acute Endangered Species - endangered species may be adversely affected. 0.1	0.05	1

Chronic Risk - there is potential for chronic risk.	1	1	N/A

For a more detailed explanation of the ecological risks posed by the use of triadimefon, refer to the “  SEQ CHAPTER \h \r 1 Environmental Fate and Effects Division Revised Risk Assessment for Triadimefon”, dated January 19, 2006.

Aquatic Organism Exposure and Risk

	1)	Fish, Invertebrate, and Aquatic Plant Toxicity

Freshwater and Estuarine/Marine Fish

Toxicity studies conducted using technical triadimefon demonstrate that it is slightly to moderately toxic to freshwater fish under acute exposure with LC50 values ranging from 4.1 ppm to 28 ppm (rainbow trout) and 10 ppm to 24.7 ppm (bluegill sunfish).   Likewise, two freshwater toxicity studies were also conducted for the major triadimefon degradate, triadimenol.  The freshwater fish acute toxicity values (LC50) for triadimenol indicate that triadimenol is slightly toxic on an acute basis.

Tables 18 and 19 summarize the data that support the acute toxicity endpoints used in assessing the risks to freshwater fish.  No triadimefon or triadimenol estuarine/marine fish acute toxicity tests were submitted to the Agency.

Table 18.  Acute Toxicity Endpoints for Freshwater Fish (Triadimefon)

Test Species/

	% a.i.	96-hr LC50 (ppm)	Toxicity

Classification	MRID No. Author/Year

Cold water fish (Rainbow trout, Oncorhynchus mykiss	96.8	4.1

Moderately toxic	43256201

Bowers/1994

Table 19.  Acute Toxicity Endpoints for Freshwater Fish (Triadimenol)

Test Species/

	% a.i.	96-hr LC50 (ppm)	Toxicity

Classification	MRID No. Author/Year

Warm water fish

(Bluegill sunfish, Lepomis macrochirus)	92	14

Slightly toxic	071469

Lamb/1981

For chronic toxicity, a freshwater fish early life-stage test using technical triadimefon showed that the most sensitive species is the rainbow trout, with a NOAEL of 41 ppb (0.041 ppm).  However, no chronic freshwater fish toxicity data were available for the degradate triadimenol.  In addition, no triadimefon or triadimenol estuarine/marine fish chronic toxicity tests were submitted.  Table 20 summarizes the data for the chronic toxicity endpoints used in assessing the risks to freshwater fish.

Table 20.  Early Life-Stage Chronic Toxicity Endpoints for Freshwater Fish

(Triadimefon)

Group

(Test Species)

	% a.i.	NOAEL (ppm)	LOAEL

(ppm)	Endpoints Affected	MRID No. Author/Year

Cold water fish

(Rainbow trout, Oncorhynchus mykiss)	93	0.041

0.116

	Growth	251243

Carlisle/1983

Freshwater and Estuarine/Marine Invertebrates

Toxicity studies conducted using technical triadimefon demonstrate that it is slightly to moderately acutely toxic to freshwater invertebrates, with LC50 values ranging from 1.6 to 11.3 ppm.  Freshwater invertebrate acute toxicity tests were also performed for the degradate triadimenol, resulting in an LC50 value of 2.5 ppm (moderately toxic).  Table 21 summarizes the data that support the acute toxicity endpoints used in assessing the risks to aquatic invertebrates.  No triadimefon or triadimenol estuarine/marine invertebrate acute toxicity tests were submitted to the Agency.

Table 21.  Acute Toxicity Endpoints for Freshwater Invertebrates

Test Species/ Flow-through	% a.i.	48-hr LC50 (ppm)	Toxicity

Classification	MRID No.

Author/Year

Triadimefon

Invertebrate (Waterflea, Daphnia magna)	Tech.	1.6	Moderately toxic 231311

Lamb/1997

Triadimenol

Invertebrate (Waterflea, Daphnia magna)	92	2.5	Moderately toxic	071469

Lamb/1981

A freshwater early life stage aquatic toxicity test using technical triadimefon is available for daphnia magna with a NOAEL of 0.052 ppm (decreased adult length).  Table 22 summarizes the data for the chronic toxicity endpoint used in assessing the risks to freshwater invertebrates.  No triadimenol freshwater invertebrate chronic toxicity data was submitted, and no triadimefon or triadimenol estuarine/marine invertebrate chronic toxicity tests were submitted.

Table 22.  Early Life-Stage Chronic Toxicity Endpoints for Freshwater Invertebrates

Group

(Test Species)

	% a.i.	NOAEL (ppm)	LOAEL

(ppm)	Endpoints Affected	MRID No. Author/Year

Triadimefon

Invertebrate (Waterflea, Daphnia magna)	94.2	0.052

0.119

Adult length	41922102

Gagliano/1991

Non-target Aquatic Plants

An aquatic plant toxicity study was performed for triadimefon on the technical formulated product on green algae, resulting in an EC50 value of 1.71 ppm.  The EC50 value for triadimenol was 3.7 ppm.  No studies were performed on vascular aquatic plant species.  Table 23 summarizes the data for the plant toxicity endpoints used in assessing the risks to aquatic plants.

Table 23.  Toxicity Endpoints for Aquatic Plants (Nonvascular)

Species	% a.i.	EC50

(ppm)	EC05 or NOAEC (ppm)	MRID No.

Author/Year

Triadimefon

Green algae

Scenedesmus subspicatus	91.5	1.71	0.1	00159558

Heimbach/1985

Triadimenol

Green algae

Scenedesmus subspicatus	94.9	3.7	0.32	266051

Mobay/1986

2)	Fish and Invertebrate Exposure

	This assessment assumes exposure to both the parent triadimefon as well as triadimenol for aquatic organisms.  OPP generally uses computer simulation models to estimate exposure of aquatic organisms, such as plants, fish, aquatic-phase amphibians, and invertebrates, to a pesticide.  These models calculate estimated environmental concentrations (EECs) in surface water using laboratory data that describe the rate at which the pesticide breaks down and how it moves into the environment.  The Pesticide Root Zone Model and Exposure Analysis Modeling System (PRZM-EXAMS) model is initially used to calculate high-end estimates of surface water concentrations of pesticide in a generic pond.  This model was used to generate EECs of total triadimefon (parent + triadimenol) in surface water.  The User’s Manual and PRZM-EXAMS model description can be consulted for additional information at: www.epa.gov/offefed1/models/water/index.htm.  No EECs are generated in instances where no toxicity was observed at concentrations above the active ingredient’s water solubility or at or above the recommended limit concentration for a particular type of study.

The Agency used PRZM-EXAMS (Exposure Analysis Modeling System) modeling to derive tier II estimated environmental concentrations (EECs) for triadimefon in surface water.  Unlike the drinking water assessment described in the human health risk assessment section of this document, the ecological water resource assessment does not include the Index Reservoir (IR) and Percent-Crop Area (PCA) factor refinements.  The IR and PCA factors represent a drinking water reservoir, not the variety of aquatic habitats, such as ponds adjacent to treated fields, relevant to a risk assessment for aquatic animals.  The assumptions used represent pesticide transport in surface water in a standard pond (10,000-m2 pond, 2-m deep), with the assumption that the small field (10-ha agricultural field) is cropped at 100%. Therefore, the EEC values used to assess exposure to aquatic organisms are not the same as the values used to assess human dietary exposure from drinking water sources.

	Several scenarios chosen to represent different U.S. regions and uses were modeled for each use and can be found in the environmental fate and effects assessment for triadimefon.  The turf scenarios gave the maximum EECs, and so were chosen for regulatory purposes.  The EEC values used to assess exposure to aquatic organisms can be found in the   SEQ CHAPTER \h \r 1 Environmental Fate and Ecological Risk Assessment (Revised) for Triadimefon, dated January 19, 2006.

	Fish and Invertebrate Risk

Fish, Aquatic Invertebrates, and Aquatic Plants

There would be no LOC exceedances for fish, aquatic invertebrates, or aquatic non-vascular plants for Bayer’s newly proposed turf maximum application rate of 2 applications of 2.7 lbs. ai/A at 14 day intervals.  There were no studies available to assess risk to aquatic vascular plants (See Table 24).

 Table 24.  Aquatic Organism RQ calculations

Crop

App.  rate (# of apps., and interval between apps.)

Peak EEC

(ppb)

 Acute Risk Quotients

 Chronic Risk Quotients

Freshwater Fish

LC50 =4100 ppb	Freshwater Invert.

LC50 = 1600 ppb	Aquatic non-vascular plants

EC50 =

17000 ppb	60 Day

EEC	21 Day

EEC	Freshwater Fish NOEAC = 41 ppb	Freshwater

Invertebrate NOEAC = 52 ppb

FL turf 2.7 lbs. a.i./acre (2 app., 14 day intervals)	40.65	<LOC	<LOC <LOC	27.2	33.36	< LOC	< LOC

	Non-target Aquatic Plants

Risks were below the Agency’s level of concern for non-target aquatic non-vascular plants. No toxicity data were available to assess risks to non-target aquatic vascular plants.

Terrestrial Organism Exposure and Risk

1)	Bird and Mammal Toxicity

Birds

	Triadimefon is classified as practically non-toxic to birds with acute oral LD50 values exceeding the highest dose tested (>4000 mg ai/kg bw) and (>2000 mg ai/kg bw) via an 8-day and 14-day test, respectively.  With dietary LC50 values between >4640 ppm to >10,000 ppm triadimefon is classified as practically non-toxic on a subacute dietary basis.

	Avian single dose oral toxicity studies were also performed on the major degradate triadimenol.  The acute oral (LD50) toxicity of triadimenol to bobwhite quail exceeded the highest dose tested (>2000 mg ai/kg) (MRID 126276).   Additionally, a triadimenol subacute dietary study was performed with mallard ducks, and no mortality or signs of toxicity were seen at any doses (LC50 >5000 ppm; MRID 00126277).  The results of both studies demonstrate that triadimenol is practically nontoxic to birds on an acute oral and subacute dietary basis.  Table 25 summarizes the data that support the acute and subacute toxicity endpoints used in assessing the risks to birds for both triadimefon and its degradate triadimenol.

Table 25.  Acute Toxicity to Birds

Endpoint

Chemical

Environment/Species

Toxicity Value Used in Risk Assessment

Reference	Toxicity Classification

Acute Toxicity to Birds

Triadimefon

Bobwhite quail

LD50 = >2000 mg ai/kg bw

MRID 41895901	Practically non-toxic

Triadimenol

Bobwhite quail

LD50 = >2000 mg ai/kg bw

MRID 071469	Practically non-toxic

Subacute Toxicity to Birds

Triadimefon

Bobwhite quail

LC50 = 8392 ppm

MRID 00050066	Practically non-toxic

Triadimenol

Mallard duck

LC50 >5000 ppm

MRID

00126277	Practically non-toxic

For chronic toxicity, avian reproduction toxicity tests were performed using technical triadimefon resulting in a NOAEL of 20 ppm ai (bobwhite quail).  In addition, avian reproduction toxicity tests were also performed for the degradate triadimenol with a NOAEL of 100 ppm ai (mallard duck).  Table 26 summarizes the data for the chronic toxicity endpoints used in assessing the risks to birds.

Table 26. Chronic Toxicity to Birds

Species	% a.i.	NOAEL (ppm ai)	LOAEL

 (ppm ai)	LOAEL Endpoints	MRID No. Author/Year

Triadimefon

Northern bobwhite	93	20	100	Eggs cracked, decrease in fertile eggs, decrease in viable embryos, hatchling, 14-day old survivors	110430 Lamb/1982

Triadimenol

Mallard duck	97	100	500	Eggs laid, decrease in viability, hatchability, 14-day survivors	40283102 Carlisle/1984

 Mammals

	Triadimefon is classified as slightly toxic to mammals on an acute basis with LD50 values of 1470 mg/kg (males) and 1090 mg/kg (females).  Acute toxicity tests showed LD50 values of 689 mg/kg (males) and 752 mg/kg (females) for the degradate triadimenol, classifying it as slightly toxic to mammals (see Table 27).

Table 27.  Summary of Acute Toxicity Endpoints for Mammals

Endpoint

Chemical

Species

Toxicity

Used in Risk

Assessment

(Most sensitive Endpoints)

Reference:

Classification

Acute Toxicity to Mammals

Triadimefon

Rat

LD50 = 1090 mg/kg (females)

MRID 00264276

Acceptable

Triadimenol

Rat

LD50 = 689 mg/kg

(males)

MRID 00125411

Acceptable

Chronic toxicity data for mammals from the 2-generation rat reproduction study    testing triadimefon indicate decreased pup weights and viability in the F1 and F2 generations and decreased litter size in the F2 generation with an offspring NOAEL of 50 ppm ai.  In addition, chronic toxicity tests for the degradate triadimenol showed decreased pup weights with a NOAEL of 100 ppm ai and a LOAEL of 500 ppm ai (see Table 28).

Table 28.  Summary of Chronic Toxicity Endpoints for Mammals

Species	Test Type/

Classification	Toxicity Values Used in Risk Assessment	Affected Endpoints	MRID No.

Triadimefon

Laboratory Rat

(Rattus norvegicus)	2-generation reproduction	Offspring NOAEL = 50 ppm

Offspring LOAEL = 1800 ppm	Decreased pup weight and viability.	00155075

92188019

92188320

Triadimenol

Laboratory Rat

(Rattus norvegicus)	2-generation reproduction	Parental NOAEL = 100 ppm

Parental LOAEL =

500 ppm

Offspring NOAEL = 100 ppm

Offspring LOAEL = 500 ppm	Decreased body weights and weight gain

Decreased pup weight

	00151248

				2)	Bird and Mammal Exposure

  TC "c.	Terrestrial Organism Exposure" \f C \l "4"

  SEQ CHAPTER \h \r 1 Pesticide residues on food items are estimated based on the assumption that terrestrial organisms are exposed to a single pesticide residue in a given exposure scenario.  Application methods for liquid triadimefon formulations include ground spray, aerial spray, and chemigation.  Additionally, granular triadimefon is broadcast on residential lawns and turf (no soil incorporation).

The Agency assessed exposure to terrestrial organisms first predicting the amount of triadimefon residues found on animal food items and then using information on typical food consumption by various species of birds and mammals to determine the amount of pesticide consumed.  Estimated exposure concentrations for terrestrial animals (via spray applications) were determined by using the standard screening-level exposure model, TREX (v.1.2) (US EPA, 2005), which calculates pesticide residues on each type of food item on a daily interval for one year.  Also, registrant supported golf course use rates and application intervals were used (2 applications @ 2.7 lbs. ai/A).

For a single application there is a linear relationship between the amount of pesticide applied and the amount of pesticide residue present on a given food item.  These relationships for the various food items are determined from the Kenaga nomogram, which is a model developed by Hoerger and Kenaga (1972) and modified by Fletcher (1994). In addition to incorporating the nomogram relationship, TREX also includes pesticide degradation in the estimation of EECs.

  SEQ CHAPTER \h \r 1 			3)	Bird and Mammal Risk

Birds

There are acute and chronic LOC exceedances for birds.  The turf maximum application rate of 2 applications of 2.7 lbs. ai/A at 14 day intervals results in acute RQ LOC exceedances that are 0.14 for short grass only and chronic RQ LOC exceedances that range from 4 to 57.  Table 29 shows the avian acute and chronic risk quotients for turf use of triadimefon.  An avian acute assessment was not conducted for granular applications because definitive avian LD50 values were not available for triadimefon (no mortalities or signs of toxicity were seen in the study at the highest exposure level).

Table 29.  Avian Dietary-Based Acute and Chronic RQs for turf uses of Triadimefon (based on NOAEC of 20 mg/kg diet) based on upper-bound Kenaga values.

Use

(Application Rate)	Food Items	Upper Bound EEC (mg/kg)	Acute Dietary-Based RQ (EEC/LC50)	Chronic Dietary-Based RQ (EEC/NOAEC)

Turf  (2.7 lbs. a.i./A, 2 applications, 14 day interval)	Short grass 1139	0.14	57

	Tall grass	522	0.06	26

	Broadleaf plants/small insects	641	0.08	32

	Fruits, pods, seeds, large insects	71	0.01	4

Mammals

For spray application, there are mammalian acute LOC exceedances (LOC > 0.5) for small and medium (15 and 35g) mammals which consume short grass treated with 2 applications @ 2.7 lbs. ai/A with a 14-day interval.   Endangered species LOCs are exceeded (LOC> 0.1) for all weight classes of mammals assessed.  Acute RQs are summarized below in Table 33.

The predicted triadimefon granular EEC values resulting from residential application at a rate of  2.7 lbs. ai/A (2 applications, 14-day interval) is 28.12 mg/ft2 (See Table 30).

Table 30.  Mammalian Dose-based Acute RQs for turf uses of Triadimefon (based on Triadimenol LD50 of 689 mg/kg in rats) based on upper-bound Kenaga values.

Spray Application

  SEQ CHAPTER \h \r 1 Use	Body Weight (g)	Adjusted LD50	Mammalian Dose-based Acute Risk Quotients

	Short grass	Tall grass	Broadleaf plants/ small insects	Fruits/pods/ large insects	Seeds

Turf (2.7 lbs. ai/A, 2 applications, 14 day interval)	15	1514	0.72	0.33 0.40	0.04	0.01

	35	1225	0.61	0.28	0.34	0.04	0.01

	1000	530	0.33	0.15	0.18	0.02	0.00

Granular Application

Use	Body Weight (g)	Mg a.i./sq ft	Adjusted LD50	Risk  Quotient

Turf (2.7 lbs. ai/A, 2 applications, 14 day interval)	15	28.12	1514	1.24

	35	28.12	1225	0.66

	1000	28.12	530	0.05

In addition, there are LOC exceedences of mammalian chronic risks ranging from 1.42 to 23 for the turf maximum application rate of 2 applications of 2.7 lbs. a.i./A at 14 day intervals (See Table 31).

  SEQ CHAPTER \h \r 1 Table 31. Mammalian Dietary-based Chronic RQs for selected uses of non-granular Triadimefon (based on triadimefon rat NOAEL of 50mg/kg diet) and upper-bound Kenaga values.

Use	Dietary-based Chronic Risk Quotients

	Short Grass	Tall Grass	Broadleaf plants	Fruits/pods/ large insects/seeds

Turf (2.7 lbs. ai/A, 2 applications, 14 day interval)	22.78	10.44	12.81 1.42

Additional/Potential Dietary Risks to Birds and Mammals

Based on the use of a fugacity-based (equilibrium partitioning) approach, an estimation of the concentration of triadimefon and its degradates in earthworms were calculated in order to determine the possible contribution of earthworm (and other terrestrial invertebrate) consumption to mammal and avian risk.    SEQ CHAPTER \h \r 1 The calculated earthworm tissue concentrations of triadimefon/triadimenol suggest that ingestion of earthworms by birds and mammals based on dietary dose (triadimefon NOAEC = 20 mg/kg diet and NOAEL = 2.5 mg/kg bw, respectively) could be another exposure pathway contributing to chronic risk, although the low earthworm concentrations would necessitate consumption of a large number of worms.

			4)	Non-target Terrestrial Plants

Non-target Terrestrial Plants

	No guideline studies evaluating the toxicity of triadimefon to terrestrial plants have been submitted to the Agency.  However, although several other studies within the Agency’s database were not suitable for use in determining toxicity endpoints, they can be interpreted qualitatively to demonstrate potential terrestrial plant risk from triadimefon.  One such study is summarized below.

	The regrowth of Kentucky bluegrass was inhibited following treatment of triadimefon.  The same study showed a height decrease in kidney bean plants.  Although the study did not provide adequate information to quantitatively calculate RQ values for non-target terrestrial plants, the results suggest that triadimefon may have negative effects on both monocot and dicot non-target terrestrial plants.  Please refer to the environmental fate and effects risk assessment for more detailed information.

Based on the supported maximum 2 applications for the golf course use pattern for a maximum single application of 2.7 lbs. a.i./acre, there would be no LOC exceedances for non-vascular aquatic plants.

	Non-target Insects

  SEQ CHAPTER \h \r 1 EPA currently does not quantify risks to terrestrial non-target insects; therefore, risk quotients are not calculated for these organisms.  Based on the acute contact toxicity study to honeybees, the LD50 for triadimefon is >25 ug ai/bee (MRID 42307804), which classifies it as practically non-toxic to honeybees.  No data were available for the degradate triadimenol.

	3.	Ecological Incidents

A review of the Ecological Incident Information System (EIIS) was completed on April 21, 2005.  No incidents involving triadimefon or its metabolite triadimenol were reported.

		4.	Endangered Species  TC "c.	Endangered Species Concerns" \f C \l "4"

The Agency’s screening level ecological risk assessment for endangered species results in the determination that triadimefon will have no direct acute effects on threatened and endangered freshwater fish, and freshwater aquatic invertebrates.  However, the assessment indicates that triadimefon has the potential for causing risk to endangered birds, mammals, and non-target plants.  Further, potential indirect effects to any species dependent upon a species that experiences effect cannot be precluded from use of triadimefon.  These findings are based solely on EPA’s screening level assessment and do not constitute “may effect” findings under the Endangered Species Act.

IV.	Risk Management, Reregistration, and Tolerance Reassessment Decision

	A.	Determination of Reregistration Eligibility and Tolerance Reassessment

  SEQ CHAPTER \h \r 1 Section 4(g)(2)(A) of FIFRA calls for the Agency to determine, after submission of relevant data concerning an active ingredient, whether or not products containing the active ingredient are eligible for reregistration.  The Agency has previously identified and required the submission of the generic (i.e., active ingredient-specific) data required to support reregistration of products containing triadimefon as an active ingredient.  The Agency has completed its review of these generic data, and has determined that the data are sufficient to support reregistration of all products containing triadimefon.

The Agency has completed its assessment of the dietary, occupational, residential, and ecological risk associated with the use of pesticide products containing the active ingredient triadimefon.  Based on a review of these data and on public comments on the Agency’s assessments for triadimefon, the Agency has sufficient information on the human health and ecological effects to make decisions as part of the tolerance reassessment process under FFDCA and reregistration process under FIFRA, as amended by FQPA.  The Agency has determined that products containing triadimefon are eligible for reregistration provided that: (i) required product-specific data are submitted; (ii) risk mitigation measures outlined in this document are adopted (including requests for deletion of certain uses); and (iii) label amendments are made to reflect these measures.  Label changes are described in Section V.  Appendix A summarizes the uses of triadimefon that are eligible for reregistration.  Appendix B identifies the generic data requirements that the Agency reviewed as part of its determination of reregistration eligibility of triadimefon, and lists the submitted studies that the Agency found acceptable.

Based on its evaluation of triadimefon, the Agency has determined that triadimefon products, unless labeled and used as specified in this document, would present risks inconsistent with FIFRA.  Accordingly, should a registrant fail to implement any of the risk mitigation measures identified in this document, the Agency may take regulatory action to address the risk concerns from the use of triadimefon.  If all changes outlined in this document are implemented, then all current risks for triadimefon will be adequately mitigated for the purposes of this determination under FIFRA.  Additionally, once an endangered species assessment is completed, further changes to these registrations may be necessary, as explained in Section IV..D..4 of this document.  Once the uses that result in risks of concern are deleted and a cancellation order is issued, the Agency will take the appropriate regulatory action under FFDCA to revoke the associated tolerances.