Document ID: EPA-HQ-OPP-2015-0061-0032
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2021-10-22T04:00Z

Tetraconazole
    
                                          
            Proposed Interim Registration Review Decision 
                                Case Number 7043 
                                          
                                          
                                         
                                 September 2021 
                                          
                                          
                                          
                                       
                                       
                                                                               
                                                                               
                                                                   Approved by:
  

Mary Elissa Reaves, Ph.D.

Director

Pesticide Re-evaluation Division
                                                                          Date:
      09/20/2021
		

                                 
                                 Table of Contents 
I. 	INTRODUCTION	3
A.	Summary of Tetraconazole Registration Review	4
B.	Summary of Public Comments on the Draft Risk Assessments and Agency Responses	5
II. 	USE AND USAGE	7
III.	SCIENTIFIC ASSESSMENTS	8
A.	Human Health Risks	8
1.	Risk Summary	8
2.	Human Incidents and Epidemiology	10
3.	Tolerances	10
4.	Human Health Data Needs	13
B.	Ecological Risks	13
1.	Risk Summary and Characterization	13
2.	Ecological Incidents	17
3.	Ecological and Environmental Fate Data Needs	17
C.	Benefits Assessment  	18
IV. 	PROPOSED INTERIM REGISTRATION REVIEW DECISION	18
A.	Proposed Risk Mitigation and Regulatory Rationale	18
B.	Environmental Justice	21
C.	Tolerance Actions	21
D.	Proposed Interim Registration Review Decision	21
E.	Data Requirements	22
V. 	NEXT STEPS AND TIMELINE	22
A.	Proposed Interim Registration Review Decision	22
B.	Implementation of Mitigation Measures	23
Appendix A:  Summary of Proposed Actions for Tetraconazole	24
Appendix B:  Proposed Labeling Changes for Tetraconazole Products	25
Appendix C: Listed-Species Assessment	29
Appendix D: Endocrine Disruptor Screening Program	30
   
	
   I. 	INTRODUCTION 
    	 
   This document is the Environmental Protection Agency's (EPA or the Agency) Proposed Interim Registration Review Decision (PID) for tetraconazole (PC Code 120603; case 7043). In a registration review decision under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), the Agency determines whether a pesticide continues to meet FIFRA's registration standard. Where appropriate, the Agency may issue an interim registration review decision before completing a registration review. Among other things, the interim registration review decision may determine that new risk mitigation measures are necessary, lay out interim risk mitigation measures, identify data or information required to complete the review, and include schedules for submitting the required data, conducting the new risk assessment and completing the registration review. For more information on tetraconazole, see EPA's public docket (EPA-HQ-OPP-2015-0061) at www.regulations.gov.
   
   FIFRA mandates the continuous review of existing pesticides. All pesticides distributed or sold in the United States must be registered by EPA based on scientific data showing that they will not cause unreasonable risks to human health or to the environment when used as directed on product labeling. In 2006, the Agency began implementing the registration review program. EPA will review each registered pesticide every 15 years. Through the registration review program, the Agency intends to verify that all registered pesticides continue to meet the registration standard as the ability to assess and reduce risk evolves and as policies and practices change. By periodically re-evaluating pesticides as science, public policy, and pesticide-use practices change, the Agency ensures that the public can continue to use products in the marketplace that do not present unreasonable adverse effects. For more information on the registration review program, see http://www.epa.gov/pesticide-reevaluation. 
   
   The Agency is issuing a PID for tetraconazole so that it can (1) move forward with aspects of the registration review that are complete and (2) implement interim risk mitigation (see Appendices 
   A and B). EPA is currently working with the U.S. Fish and Wildlife Service and the National Marine Fisheries Service (the Services) to improve the consultation process for national threatened and endangered (listed) species for pesticides under the Endangered Species Act (ESA). The Agency has not yet fully evaluated tetraconazole's risks to federally listed species. However, EPA will complete its listed-species assessment and any necessary consultation with the Services before completing the tetraconazole registration review. Before completing registration review, EPA will also complete endocrine screening for tetraconazole under the Federal Food, Drug, and Cosmetic Act (FFDCA). For more information on the listed-species assessment and the endocrine screening for the tetraconazole registration review, see Appendices C and D.  
   Tetraconazole is a systemic fungicide used to control and suppress fungal diseases, such as powdery mildew, leaf and pod spot, white mold, and common and southern rust. Tetraconazole is registered for application to legume vegetable crop subgroup 6C (dried shelled pea/bean), fruiting vegetables crop group 8, cucurbit vegetables crop group 9, low growing berry subgroup 13-07G, and small fruit vine climbing, except fuzzy kiwifruit, subgroup 13-07F, fruiting vegetables crop group 8-10, rapeseed subgroup 20A, barley, beans (dry type), blueberry, canola, corn (field and pop), gooseberry, grapes, peanuts, pecans, soybeans, strawberry, sugar beets, and wheat. Tetraconazole is a member of the triazole class of fungicides. It is not registered for use on non-agricultural sites. Tetraconazole end-use products can be formulated as emulsifiable concentrates, flowable concentrates, and oil-in-water emulsions. Tetraconazole can be applied to the foliage by aerial, airblast, chemigation, and ground equipment. 
   
   This document is organized in five sections: the Introduction, which includes this summary and a summary of public comments and EPA's responses; Use and Usage, which describes how and why tetraconazole is used and summarizes data on its use; Scientific Assessments, which summarizes EPA's risk and benefits assessments, updates or revisions to previous risk assessments, and provides broader context with a discussion of risk characterization; the Proposed Interim Registration Review Decision, which describes any mitigation measures proposed to address risks of concern and the regulatory rationale; and, lastly, the Next Steps and Timeline for completion of this registration review. 
   
 Summary of Tetraconazole Registration Review 
   
   Pursuant to 40 CFR § 155.50, EPA formally initiated registration review for tetraconazole with the opening of the registration review docket for the case. The following summary highlights the docket opening and other significant milestones that have occurred thus far during the registration review of tetraconazole.   
    
   ::    October 2015  -  EPA posted the Tetraconazole Preliminary Work Plan (PWP), Tetraconazole; Human Health Assessment Scoping Document in Support of Registration Review (August 26, 2015), Registration Review; Preliminary Problem Formulation for the Environmental Fate, Ecological Risk, Endangered Species, and Drinking Water Assessments for Tetraconazole (August 26, 2015), and other supporting documents were posted to the docket for a 60-day public comment period.  
    
    March 2016  -  EPA posted the Tetraconazole Final Work Plan (FWP) to the public docket. The Agency received one public comment from Physicians Committee for Responsible Medicine on the PWP.  The comment did not change the schedule, risk assessment needs, or anticipated data requirements for registration review. The FWP identified several environmental fate and ecological data needs.
    
    January 2017 -  The Agency issued a Generic Data Call-In (GDCI-120603-1573) for tetraconazole to obtain data needed to conduct the registration review risk assessments. All the required data have been submitted and the GDCI has been satisfied.  
      
    March 2021  - The Agency published Tetraconazole. Draft Human Health Risk Assessment in Support of Registration Review (December 11, 2020), Tetraconazole: Draft Ecological Risk Assessment for Registration Review (December 2, 2020), and other supporting documents for a 60-day public comment period. The Agency received public comments from seven sources. The Agency has summarized and responded to these comments in Section 1.B below.  
         
    September 2021  -  The Agency completed a PID for tetraconazole and posted it to the docket for a 60-day public comment period. Along with the tetraconazole PID, EPA posted the following document to the public docket: 

          Tetraconazole: Tier I Update Review of Human Incidents and Epidemiology for Draft Risk Assessment (November 23, 2020).
          Tetraconazole: Response to Public Comments on the Draft Ecological Risk Assessment (August 18, 2021).
      
 Summary of Public Comments on the Draft Risk Assessments and Agency Responses 

During the 60-day public comment period for the tetraconazole draft risk assessments, which opened on March 8, 2021 and closed on May 7, 2021, the Agency received public comments from seven sources. Comments were received from the United States Department of Agriculture (USDA), Southern Minnesota Beet Sugar Cooperation (SMBSC), National Agricultural Aviation Association (NAAA), American Soybean Association (ASA), California Fresh Fruit Association (CFFA), American Crystal Sugar Company (ACSC), and TSG Consulting on behalf of Isagro, a technical registrant. The Agency has summarized and responded to all substantive comments and comments of a broader regulatory nature below. The Agency thanks all commenters for participating and has considered their comments in developing this PID. 

Comments Submitted by TSG Consulting on behalf of Isagro (Docket ID: EPA-HQ-OPP-2015-0061-0023)
   
Comment:  The commenter does not believe that the Pesticide in Water Calculator (PWC) model is realistic. While model estimates for the water column and benthos for daily 1-in-10-year average Estimated Environmental Concentrations (EECs) are above 1 μg/L, the monitoring data provided in Section 8.1.2 of EPA's ecological risk assessment indicate that levels of tetraconazole in surface and ground water are negligible. Modeling of ground water levels by the European Food Safety Authority and field study data support tetraconazole levels of less than 0.1 μg/L in ground water.

EPA Response:  EPA's aquatic exposure assessments typically use high-end exposure scenarios to estimate aquatic exposure using the PWC. These high-end exposure estimates are used to avoid underestimating real-world exposures and are protective of potential risks to aquatic taxa. Monitoring data reported in the risk assessment are non-targeted and sampling may not occur near sites where tetraconazole is applied or coincident with applications of tetraconazole, so they cannot be used to quantify risks to aquatic organisms. 

Comment: EPA concluded that the risk estimate for small birds feeding on short grasses at pecan use sites exceeds the Level of Concern (LOC) of 0.5. However, the upper-bound dose-based EEC for that population is 62 mg/kg bw. The relevant toxicological endpoint is an acute LD50 value of 131 mg/kg bw, so the Risk Quotient (RQ) should be calculated as 62 divided by 131 or 0.47, rather than 0.66 as reported in the risk assessment, and would not exceed the LOC. 

EPA Response: The Agency's modeling is based on an adjusted LD50 method to account for groupings by weight class (20, 100 or 1000g birds). The adjusted LD50 for a 20g bird, derived from the empirical endpoint for the bobwhite quail (131 mg/kg-bw), is 94 mg/kg-bw. The maximum EEC (62 mg/kg-bw) divided by the adjusted LD50 (94 mg/kg-bw) yields an RQ of 0.66 (for the pecan use pattern, short grass food source), which is slightly above the LOC of 0.5. Even though the Agency calculated an RQ is excess of the LOC, it acknowledges that the smallest class of birds typically does not rely on short grass as a food source.

Comment: The commenter noted the uncertainty in EPA's honey bee risk assessment and believes that the weight of evidence indicates tetraconazole is safe as currently used. Isagro previously submitted nectar and pollen residue data from a tunnel experiment that showed residue concentrations much lower than those derived using the Agency's Bee-Rex model. In addition, bees in the tunnel study did not manifest any adverse effects.

EPA Response: The Agency concluded that the submitted tunnel semi-field study had major shortcomings, including insufficient numbers of replicates, testing at only one dose level and a single application method, a shortened test duration, and failure to quantify exposure to the test material. Because of these deficiencies, the tunnel study had limited value in addressing the uncertainties related to chronic exposure and effects.  

Comments submitted by USDA (Docket ID: EPA-HQ-OPP-2015-0061-0024)

Comment: USDA provided information on and context for the benefits associated with the use of tetraconazole on corn, grapes, strawberries, soybean, and sugar beets. USDA also noted that average application rates for some uses of tetraconazole fall below the maximum allowable rates assessed by the Agency, so that the risk estimates in the ecological risk assessment may overstate risk in some instances. 
 
EPA Response: EPA has considered the overall risk profile and the benefits associated with the use of tetraconazole and has concluded that the benefits can be preserved when a few targeted risk management measures are implemented. The proposed measures are discussed in Section IV of this document and Appendix B. 

Comments Submitted by NAAA (Docket ID: EPA-HQ-OPP-2015-0061-0026)

Comment: The NAAA provided comments regarding the spray drift analysis conducted in the draft risk assessment, particularly concerning the spray drift model, AgDRIFT, and the inputs used in the model (e.g., aircraft type, swath width and displacement, number of passes, wind speed, height for wind speed measurement, boom length and boom drop, droplet size, atmospheric stability, and surface roughness). The NAAA believes that the tier-1 component of the AgDRIFT model is inadequate because some of the assumptions it uses are unrealistic. The NAAA recommended the use of the Multiple Application Assessment Method (MAAM) to model drift potential for products that can be applied multiple times annually on a crop. The NAAA also recommended a refined assessment with a higher tiered model. 
 
EPA Response: AgDRIFT is the currently approved model for evaluating potential spray drift from a pesticide application. The Agency appreciates the additional suggestions provided by NAAA for revising the AgDRIFT modeling inputs and continues to work with industry to update and improve modeling methods to better reflect typical application practices. At the December 2020 Center of Excellence in Regulatory Science in Agriculture (CERSA) workshop, EPA, NAAA, and other stakeholders discussed these potential refinements for AgDRIFT modeling. EPA is currently reviewing these suggestions and will consider them for future risk assessment. However, modeling for a national‐level assessment is first conducted using maximum application rates, limitations, and instructions listed on the pesticide labels containing tetraconazole. In the absence of specific use directions and application restrictions implemented across all product labels, default assumptions (based on empirical data) are used. 

Comments Submitted by ACSC, SMBSC, CFFA, ASA (Docket IDs: EPA-HQ-OPP-2015-0061-0018, -0020, -0025, and -0028, respectively)
 
Comment: Each of these groups commented on the importance of continued availability of tetraconazole in their industries for control of fungal diseases in sugar beets, table grapes, and soybeans. Their remarks focus on their industries' promotion of integrated pest management (IPM) and fungicide resistance management and the part that tetraconazole plays in those efforts. All four commenters requested that the Agency continue to allow the use of this crop protection tool.  

EPA Response: EPA has considered the overall risk profile and the benefits associated with the use of tetraconazole and has determined that the benefits can be preserved through targeted risk mitigation. The proposed mitigation measures are discussed in Section IV of this document and Appendix B. The Agency welcomes stakeholder comments on the risk management proposal for tetraconazole.  

II. 	USE AND USAGE  
                                                                                                     
Tetraconazole is a fungicide registered for use on various agricultural sites with no non-agricultural sites registered. Agricultural uses are registered on the following crop sites and specific crop groups as defined by 40 CFR §180.41: barley; corn; wheat; peanuts; soybeans; sugar beets; pecans; small fruit vine climbing subgroup except fuzzy kiwifruit (subgroup 13-07F); low growing berries (subgroup 13-07G); rapeseeds (subgroup 20A); dried shelled pea and beans (except soybean) (subgroup 6C); fruiting vegetables (except cucurbits) (group 8); and cucurbit vegetables (group 9). Tetraconazole products can be formulated as oil in water emulsions, emulsifiable concentrates and flowable concentrates. Tetraconazole is applied as a postemergence foliar application by ground, aerial or irrigation broadcast equipment. For more details, see the Tetraconazole Pesticide Label Use Summary available in this docket. According to usage data from grower surveys between 2015 and 2019, an average of one million total crop acres were treated annually with approximately 70,000 pounds of tetraconazole. Soybeans comprised nearly half of the national usage of tetraconazole with 500,000 soybean acres treated with 30,000 pounds of active ingredient (a.i).[9] Although soybean was the top use site in terms of pounds applied for tetraconazole applications, less than 1% of soybean acres are treated nationally. Based on percent crop treated (PCT), notable use sites are: strawberries (20 PCT; 2,000 lbs applied to 40,000 total acres), sugar beets (15 PCT; 20,000 lbs applied to 200,000 total acres), wine grapes (15 PCT; 4,000 lbs applied to 100,000 total acres), raisin grapes (10 PCT; 600 lbs applied to 10,000 total acres), and table grapes (10 PCT; 300 lbs applied to 8,000 total acres). Application rates in these top usage crops range from 0.037 lbs a.i. per acre in wine grapes to 0.097 lbs a.i. per acre in sugar beets, with an average application rate 0.065 lbs a.i. per acre across all surveyed use sites.[10] In each of the major use sites, the average number of applications was between one and two per year: one application per year on soybeans, one application on grapes (raisin, table, wine) and sugar beets, and 1.7 applications on strawberries.  For more details, see the Tetraconazole Summary Use and Usage Matrix.               
   
III.	SCIENTIFIC ASSESSMENTS 
    
      A.	Human Health Risks  
    
The Agency has summarized the 2021 tetraconazole human health risk assessment below. The Agency used the most current science policies and risk assessment methodologies to prepare this risk assessment in support of the registration review of tetraconazole. For additional details on the human health assessments for tetraconazole, see Tetraconazole: Draft Human Health Risk Assessment in Support of Registration Review, Tetraconazole. Acute and Chronic Dietary (Food and Drinking Water) Exposure and Risk Assessment to Support the Human Health Risk Assessment for Registration Review, and Tetraconazole. Occupational and Residential Exposure Assessment for Registration Review, in EPA's public docket (EPA-HQ-OPP-2015-0061).
   
 Risk Summary  

No cancer risk assessments were conducted because tetraconazole is classified as "Not likely to be carcinogenic to humans at levels that do not cause increased cell proliferation in the liver" and quantification of carcinogenic potential is not required since the chronic reference dose is protective of any potential carcinogenicity.
   
Dietary (Food +Water) Risks

Acute and chronic risk assessments were conducted. The acute (food and drinking water) risk assessment resulted in risks below the Agency's LOC for the general population and all population subgroups. The mostly highly exposed population subgroup is all infants with a risk estimate of 4.9% of the acute Population Adjusted Dose (aPAD; LOC=100% of the aPAD). Females 13-49 were assessed with a separate aPAD=0.225 mg/kg/day and had a risk estimate of 3.7% of the aPAD.  

The chronic dietary risk estimate (food and drinking water) was also below the Agency's LOC for the general U.S. population and all population subgroups. The most highly exposed population subgroup is all infants with a risk estimate of 11% of the chronic Population Adjusted Dose (cPAD; LOC=100% of the cPAD). Thus, there are no dietary risks of concern identified for tetraconazole.  

Residential Handler and Post-Application Risks

Residential handler exposure was not assessed because there are no registered or proposed residential uses of tetraconazole that would result in residential handler exposures. A residential post-application risk assessment was not needed because tetraconazole is not registered for use on residential sites.

Non-occupational Spray Drift Risks

Spray drift is a potential source of exposure to those nearby pesticide applications. Since a dermal endpoint was not selected, only children's (1 to <2 years old) incidental oral risk estimates were quantitatively assessed from indirect exposure to tetraconazole related to spray drift; the assessment did not result in any risks of concern at field edge for ground boom, aerial, or airblast applications with Margins of Exposure (MOEs) ranging from 12,000 to 22,000 (LOC=100). Therefore, the Agency concluded that spray drift exposure does not represent a potential risk of concern.

Aggregate Risks

In an aggregate assessment, EPA considers the combined pesticide risks from three major sources: food, drinking water, and residential exposures. The Agency sums the exposures from these sources and compares the aggregate risk to quantitative estimates of hazard. For tetraconazole, the aggregate exposure is equivalent to the dietary exposure because there are no residential exposures. The aggregate risk estimate is not of concern. 

Cumulative Risks 

The Agency has not made a common-mechanism-of-toxicity-to-humans finding for tetraconazole and any other substance. Although the triazole fungicides all share the metabolite 1,2,4-triazole and its acid-conjugated metabolites, these substances do not contribute to the toxicity of the parent triazoles. The Agency has determined that the toxicological effects resulting from exposure to these metabolites are different from that resulting from exposure to tetraconazole. Tetraconazole does not appear to produce any other toxic metabolites produced by other substances. Therefore, EPA has premised this PID and the underlying risk assessments on the belief that tetraconazole does not have a common mechanism of toxicity with other substances. 

Occupational Handler Risks

Occupational handlers are individuals involved in the pesticide application process. A quantitative dermal risk assessment was not required since there is no dermal hazard for tetraconazole. Only inhalation risks were assessed. All occupational handler scenarios for the registered uses resulted in inhalation risk estimates that are not of concern with label-directed clothing and Personal Protective Equipment (PPE) requirements (i.e., no respirator), with inhalation MOEs ranging from 1,700 to 850,000 (where MOEs above the LOC of 30 are not considered to be risks of concern).   

Occupational Post-Application Risks

Occupational post-application dermal exposure was not assessed for tetraconazole because there is no dermal hazard identified. Based on the Agency's current practices, a quantitative occupational post-application inhalation exposure assessment was not conducted. However, the occupational handler assessment is expected to be protective of most post-application inhalation exposures.
   
 Human Incidents and Epidemiology 
   
As of EPA's latest search on November 23, 2020, there was one case involving tetraconazole reported to the Main Incident Data System (IDS) from January 1, 2015 to September 30, 2020 and none in the Aggregate IDS. The incident involved the single active ingredient tetraconazole only. This incident was classified as moderate severity.  

A review of Sentinel Event Notification System for Occupational Risk (SENSOR)-Pesticides between 2012-2017, there were two cases reported stemming from one event, involving tetraconazole and multiple other active ingredients. The individuals involved in the case were agricultural workers. One case was moderate in severity and one case was low in severity.  In the case of the moderate severity incident, the worker was conducting maintenance on pesticide application equipment. The worker went to the emergency room for treatment of symptoms, including headache, dizziness, diarrhea, nausea, and vomiting. The other worker was picking mustard in a field and came into contact via drift from a fungicide application being conducted nearby. The worker experienced left arm numbness and tingling and was unable to breathe; other symptoms were headache, nausea, dizziness, fatigue, and body aches. The worker went to the emergency room for treatment and the symptoms were resolved after two days.  

Tetraconazole is not included in the Agricultural Health Study. The Agency intends to monitor human incidents for tetraconazole and will conduct additional analyses if necessary.
 
 Tolerances  

Tetraconazole is registered for uses that result in residues in or on food. Generally, a tolerance or tolerance exemption -- and for some uses, FDA regulations or food contact notifications -- must cover the residues or the affected food is considered adulterated. All of the necessary tolerances, exemptions, and FDA clearances are in place to cover residues resulting from tetraconazole's legal use.

The Agency has established tolerances for tetraconazole under 40 CFR §180.557.  There are no Codex Maximum Residue Limits (MRLs) established for tetraconazole. The U.S. and Canadian residue definitions are harmonized as are the ruminant meat tolerance levels. Harmonization with Canadian MRLs for fat (cattle, goat, horse, and sheep), meat byproducts, milk, and sugar beets are not appropriate as the levels are too low for enforcement of registered U.S. uses.  

The tetraconazole tolerance expression in 40 CFR 180.557 conforms to current Agency practice. During the risk assessment process, EPA determined that minor changes to some of the existing tolerances are necessary to cover residues in or on food from the uses of tetraconazole. The Agency is now following the Organization for Economic Cooperation and Development (OECD) rounding class practice, which does not recommend adding a trailing zero. EPA is also anticipating revisions to some established tolerances to correct commodity definitions. The anticipated tolerance changes are noted in Table 1. The Agency intends to undertake these tolerance actions pursuant to its Federal Food, Drug Cosmetic Act (FFDCA) authority.  

Table 1.  Summary of Anticipated Tolerance Revisions for Tetraconazole: 40 CFR §180.557(a).
Commodity/Correct Definition
Established Tolerance (ppm)
Anticipated Tolerance (ppm)
Comments

Barley, bran
1.0
1
Corrected values to be consistent with OECD Rounding Class Practice.
Barley, flour
0.50
0.5

Barley, grain
0.30
0.3

Beet, sugar, dried pulp
--
0.2
Commodity definition revision; corrected values to be consistent with OECD Rounding Class Practice.
 Beet sugar, dried pulp
0.20
Remove

Beet, sugar, molasses
--
0.25
Commodity definition revision
 Beet sugar, molasses
0.25
Remove

Beet, sugar, root
--
0.15

 Beet sugar, root
0.15
Remove

Berry, low growing, subgroup 13-07G
--
0.25

 Low growing berry subgroup 13-07G, except cranberry
0.25
Remove

Cattle, meat byproducts, except liver 
--
0.15

Cattle, meat byproducts (except liver)
0.15
Remove

Cattle, liver
1.50
1.5
Corrected values to be consistent with OECD Rounding Class Practice.
Goat, meat byproducts, except liver
--
0.15
Commodity definition revision.
Goat, meat byproducts (except liver)
0.15
Remove

Goat, liver
1.50
1.5
Corrected values to be consistent with OECD Rounding Class Practice.
Grain, aspirated fractions
4.0
4

Grain, cereal, forage, fodder, and straw, group 16
7.0
7

Hog, meat byproducts, except liver
--
0.01
Commodity definition revision.
Hog, meat byproducts (except liver)
0.01
Remove

Horse, meat byproducts, except liver
--
0.15

 Horse, meat byproducts (except liver)
0.15
Remove 

Horse, liver
1.50
1.5
Corrected values to be consistent with OECD Rounding Class Practice.
Peanut, oil
0.10
0.1

Rapeseed subgroup 20A
0.90
0.9

Sheep, liver
1.50
1.5

Fruit, small, vine climbing, except fuzzy kiwifruit, subgroup 13-07F
--
0.2
Commodity definition revision; corrected values to be consistent with OECD Rounding Class Practice.
Small fruit vine climbing, except fuzzy kiwifruit, subgroup 13-07F
0.20
Remove

Sheep, meat byproducts, except liver
--
0.15
Commodity definition revision.
Sheep, meat byproducts (except liver)
0.15
Remove

Soybean, refined oil
0.80
0.8
Corrected values to be consistent with OECD Rounding Class Practice.
Vegetable, foliage of legume, except soybean, subgroup 7A
8.0
8

Vegetable, fruiting, group 8-10
0.30
0.3

Wheat, germ
0.50
0.5

  ppm=parts per million; equivalent to milligrams per kilogram (mg/kg)

The Agency notes that some product labels list use sites for crop group 9 and crop group 8-10. A tolerance has been established for crop group 8-10, so labels should be updated to identify only crop group 8-10.
   
 Human Health Data Needs 
   
The human health database for tetraconazole is considered complete. The Agency does not anticipate any further human health data needs for tetraconazole. 
   
 Ecological Risks 
 
The Agency has summarized the 2020 ecological risk assessment below. The Agency used the most current science policies and risk assessment methodologies to prepare a risk assessment in support of the registration review of tetraconazole. For additional details on the ecological assessment for tetraconazole see the Tetraconazole: Draft Ecological Risk Assessment for Registration Review, in EPA's public docket (EPA-HQ-OPP-2015-0061). 
                            
 Risk Summary and Characterization
               
Terrestrial Risks

Mammals

No acute risks of concern were identified for mammals. None of the acute dose-based Risk Quotients (RQs) exceeded the acute LOC of 0.5. The likelihood of mortality from acute exposure is considered low and not of concern. 

Chronic mammalian risks were based on increased mortality (9%) and gestation time (2%) for parent animals. Potential chronic risks of concern were identified for mammals. The chronic LOC for mammals is 1.0.

On-field risk estimates

For tetraconazole applied to the field, the upper-bound Kenaga dietary-based RQs range up to 5.5 (pecan); there also are chronic dietary-based exceedances of the LOC for most food sources for tetraconazole applications to grapes and sugar beets. The upper-bound Kenaga dose-based RQs range up to 34 (also pecan); there are also LOC exceedances for applications to sugar beets and grapes for various food sources and size classes of mammals. Additional evidence for chronic risk concerns includes LOC exceedances based on mean Kenaga values for applications to sugar beets and pecans and at the Lowest Observed Adverse Effects Level (LOAEL) for all registered use sites. 

The Agency also assessed how long after application residues in the field would result in LOC exceedances. Based on upper-bound Kenaga values and the No Observed Adverse Effects Level (NOAEL) and the LOAEL, the greatest number of days before the RQs dropped below the LOC is 123 and 83 days, respectively. The number of days based on mean Kenaga values is 104 and 62 days, respectively. 

Off-field risk estimates 

Exposures outside the treated field resulting from drift are quantified as the distance from the field edge at which the RQ will no longer exceed the LOC (the "effects distance"). Based on upper-bound Kenaga values, mammalian chronic effects distances are estimated for three representative crops -- grape (<10 feet), sugar beets (20 feet), and pecans (30 feet) for ground application with very fine to fine spray droplet sizes. For aerial applications, the effects distances are estimated at 270 feet, 740 feet, and >997 feet for those three crops, respectively.   

Consumption of aquatic prey

The Agency also evaluated potential risks to mammals from the bioconcentration of tetraconazole in aquatic food webs. The RQs (2.8 to 5.3) exceed the chronic LOC of 1.0 for all six assessed types of predator species on a dose-basis. Dietary-based RQs do not exceed the LOC. 
 
Birds (Surrogates for Reptiles and Terrestrial-Phase Amphibians)

The Agency identified potential acute and chronic risks of concern for birds, reptiles, and terrestrial-phase amphibians exposed to tetraconazole. The acute LOC is 0.5. Chronic avian risks were based on mortality (15.9%) at 14 days and body weight reductions (7.48%) in 14-day old survivors. The chronic LOC is 1.0.

On-field risk estimates

The only acute risks of concern are associated with the pecan use pattern with a dose-based RQ of 0.66 for small birds consuming short grass; subacute dietary based RQs were all below the LOC. As noted previously, small birds typically do not use short grass as a food source.

Chronic dietary-based RQs exceed the LOC in grapes, sugar beets, and pecans for some or most food items. Upper-bound Kenaga-based RQs ranged up to 4.6. Additional evidence for chronic risk concerns includes LOC exceedances at the mean Kenaga values for pecan applications only as well as some LOC exceedances at the Lowest Observed Adverse Effects Concentration for a few foraging groups (applications to sugar beets and pecans only).

The Agency also assessed how long after application residues in the field would result in LOC exceedances. Based on upper-bound Kenaga values and the No Observed Adverse Effects Concentration, residues would result in exceedances of the LOC for up to 63 days and 36 days, respectively.  

Off-field risk estimates

Based on upper-bound Kenaga values, mammalian off-field chronic effects distances for ground applications (very fine to fine spray droplet sizes) exceed the chronic risk LOC less than 10 feet from the field edge (all use sites). Aerial application effects distances are estimated for grape (0 feet), sugar beet (20 feet), and pecans (100 feet). 

Consumption of aquatic prey

The Agency concluded that there were no potential acute or chronic risks of concern associated with consumption of aquatic prey by the avian predator species assessed (including sandpipers, herons, and ospreys). 

Terrestrial Invertebrates (honey bees)

The acute LOC for terrestrial invertebrates is 0.4, the chronic LOC is 1.0. The chronic endpoint identified for adult honey bees is a 10.2% reduction in food consumption. 

On-field risk estimates

Several registered tetraconazole use sites are not attractive to bees (i.e., barley, pecan, wheat) and most sugar beets are harvested prior to bloom. For these use sites, on-field exposure potential and risk are considered to be low. Other tetraconazole use sites are attractive to Apis and/or non-Apis bees and some utilize managed pollinator services.

All Tier I acute and chronic bee contact and oral toxicity studies are classified as supplemental and are not suitable for quantitative risk assessment. RQs have not been calculated and the data have been used for characterization purposes only. Based on the supplemental data, acute exposures for adult and larval bees on all assessed use sites are well below the experimental doses where acute mortality was observed for adult and larval bees. Thus, the likelihood of mortality from acute exposures in the field is considered low. 

Data from the chronic studies indicate that estimated chronic exposures for adult nectar foragers on all assessed use sites are above the experimental doses where the chronic effects were observed for adult bees. For larval worker bees, estimated chronic exposures for all assessed uses are below the larval bee study endpoints.

Higher Tier data have also been submitted. Data from the tunnel study are suitable for qualitative purposes only. Again, RQs were not calculated but measured exposures indicate that actual exposures from nectar and pollen are much lower than modeled concentrations. No effects were observed on colony mortality, brood development, or flight activity. 

Off-field risks to pollinators were not assessed because there are uncertainties about the toxicological endpoints.  

Terrestrial Plants

Available seedling emergence and vegetative vigor data suggest that the likelihood of adverse effects on terrestrial plants from exposure to tetraconazole at currently registered use rates is low. A 2016 incident report is discussed below. 

Aquatic Risks

Freshwater and Estuarine/Marine Fish (Freshwater Fish Serve as Surrogates for Aquatic-Phase Amphibians)

No potential acute or chronic risks of concern for freshwater fish and estuarine/marine fish exposed to tetraconazole have been identified and no risks of concern are expected for these taxa.

Freshwater and Estuarine/Marine Water Column Invertebrates

The Agency determined that there are no potential acute or chronic risks of concern for freshwater and estuarine/marine invertebrates in the water-column from exposure to tetraconazole as a result of currently registered uses. 

Freshwater and Estuarine/Marine Benthic Invertebrates 

Benthic invertebrates are those residing at the bottom of water bodies or in the sediment. Acute toxicity data are not available for freshwater or estuarine/marine benthic invertebrates. No chronic risks were identified for freshwater or marine/estuarine benthic invertebrates exposed to tetraconazole. 

Aquatic Vascular and Non-Vascular Plants

The Agency has concluded that there are no risks of concern to aquatic plants from exposure to tetraconazole use. 

Water Monitoring Data

As noted in the 2020 ecological risk assessment, water quality data were obtained from the Water Quality Portal and the California Department of Pesticide Regulation Surface Water Database.[,] In the former, there were no reported detections of tetraconazole in more than 18,000 surface water samples analyzed for tetraconazole. In the latter, there were 22 detections of tetraconazole in 1,092 surface water samples. Modeled EECs are one to two orders of magnitude greater than the maximum concentration detected. The available ground water database showed no detects in over 2,000 samples.

 Ecological Incidents                                  
 
A search of the Incident Data System (IDS) for tetraconazole was conducted for reports between the time tetraconazole was first registered until June 15, 2020. The review yielded three individual incident reports between 2016 and 2018 in which adverse ecological effects were observed after applications of tetraconazole. One incident each was recorded for plants, bees, and fish. The three incidents were either associated with registered uses or uses of unknown legality. While the incidents involving bees and fish were assigned a certainty index of "unlikely", the incident involving plants was characterized as "possible" for being associated with tetraconazole exposure. In this 2016 incident, an application of tetraconazole and other pesticides to 96 acres of grape vineyards resulted in 67 acres of blemished fruit.   

Please see the Tetraconazole: Preliminary Ecological Risk Assessment and Endangered Species Assessment for Registration Review for more information about reported ecological incidents for tetraconazole. The Agency intends to conduct ongoing ecological incident monitoring for tetraconazole and additional analyses if that monitoring indicates risks of concern to nontarget organisms.

 Ecological and Environmental Fate Data Needs       
   
The Agency issued a Generic Data Call-In (GDCI-120603-1573) in May 2018. The environmental fate and ecological effects database for tetraconazole is considered complete, except for studies identified in Table 2. below: 

Table 2. Registration Review DCI Pollinator Data Status
Identifier
Study Type
Study Classification
(More) Data Needed?
 MRID
DP Barcode
                                Tier I Studies
SS-1253
Honey bee Larvae Chronic (Multiple Dose) Toxicity Test
Supplemental
YES
 50486004
450077
SS-1254
Honey bee Adult Chronic Oral Toxicity Test: Feeding Study
Supplemental
YES
50301601
441364
SS-1257
Honey bee Larvae Chronic (Repeated Dose) Oral Toxicity Test
Supplemental
YES
50709601
450077
                                Tier II Studies
SS-1315
Semi-Field Tunnel & Field Trial Residue Study 
Acceptable[1]
YES
50790602
441364
SS-1353
Semi-Field Tunnel & Field Trial Residue Study
Acceptable[1]
YES
50790602
441364
The need for Tier III data will be determined after Agency review of lower tier data.
[1]Biological results are classified as acceptable; chemical fate results are classified as supplemental and useful for risk characterization only. 
   
A complete Tier I dataset is needed before the appropriate design can be developed for the Tier II data. The Tier II testing plan will need to cover the registered uses of tetraconazole through testing in representative plant types in the relevant use groups. The Agency will work with the registrants on the Tier II testing plan.
 
The Agency does not anticipate any other environmental fate or ecological effects data needs for 
tetraconazole at this time.                                               

 Benefits Assessment   
         
Tetraconazole is a triazole fungicide that inhibits sterol biosynthesis in phytopathogenic fungi. Tetraconazole belongs to Code 3 as per Fungicide Resistance Action Committee. Tetraconazole has systemic properties within the plant, which make it effective in both preventing fungal infection and suppressing disease development in plants. Tetraconazole effectively controls/manages frogs-eye leaf spot, anthracnose, brown leaf spot, white mold, and rust disease in soybean.[,] Strawberry growers use tetraconazole to control/manage powdery mildew.[19,] On sugar beet, tetraconazole is mainly used to control/manage Cercospora leaf spot disease.[19,] On grapes (wine, table, and raisins), growers use tetraconazole in controlling/managing powdery mildew disease that can cause significant yield and quality losses.[19,] Overall, tetraconazole helps preserve crop yields and quality. 

 IV. 	PROPOSED INTERIM REGISTRATION REVIEW DECISION 
 
      A.	Proposed Risk Mitigation and Regulatory Rationale 
 
The Agency has reviewed the risks and benefits associated with the registered uses of tetraconazole in developing this Proposed Interim Registration Review Decision. EPA has concluded that some changes are needed in order for tetraconazole to meet the standard for registration, based on the risks and benefits as discussed in Sections III and IV of this document. In some cases, the Agency is proposing changes to tetraconazole labels for clarity, consistency across the labels as a whole, and/or to conform with generic updates to labeling. The Agency has discussed the risk management approach with the registrants, and they have tentatively agreed with the proposed measures.

At this time, the Agency has determined that there are no human health risks of concern for tetraconazole, but the Agency is proposing to update glove and respirator language where glove and respirators are already on the label. There are also potential ecological risks of concern primarily to mammals and birds. To address the potential ecological risks, the Agency is proposing to update advisory spray drift language and surface water advisory language for product labels. In addition, the Agency is proposing the uniform adoption of fungicide resistance management label language.  

The Agency has concluded that the proposed label changes for tetraconazole are not likely to adversely impact stakeholders. In discussions with the Agency on August 3, 2021, representatives of the technical registrants tentatively agreed to the proposed risk mitigation measures. The proposed labeling is summarized in Appendix A and detailed in Appendix B.  

 Proposed Label Mitigation: Spray Drift Management

To address potential risks to wildlife, particularly birds, mammals, and pollinators, the Agency is proposing new and updated advisory spray drift management language for tetraconazole labels. The proposed labeling is designed to reduce off-target spray drift and consistently protect against a baseline level of spray drift across all tetraconazole products. Although the Agency is not making a complete endangered species finding at this time, these label changes are expected to reduce the extent of exposure and may reduce risk to listed species whose range and/or critical habitat co-occur with the use of tetraconazole. For the text of the proposed advisory spray drift language, see Appendix B.

Spray drift labeling language does not address on-field risks to birds, mammals, or pollinators. Based on the extent and magnitude of those potential risks and the benefits associated with the use of tetraconazole, no additional mitigation is proposed.  

 Proposed Label Mitigation: Surface Water Advisory

The Agency is proposing that tetraconazole labels be revised to update and standardize existing environmental hazard warnings to be consistent across all product labels and to reduce exposure to aquatic organisms. Tetraconazole has environmental fate properties indicating that it may persist in surface water. Therefore, the Agency is proposing an updated surface water advisory to warn users of the potential for surface water contamination. For the text of the proposed surface water advisory, see Appendix B.  

 Proposed Label Clarification: Updated Glove Statement 

The Agency proposes to update the glove statements on current tetraconazole labels, consistent with Chapter 10 of the Label Review Manual. In particular, EPA proposes removing any references to specific categories in EPA's chemical-resistance category selection chart and specifying the appropriate types of gloves. This change applies only to labels that already require gloves, and the proposed clarification does not fundamentally change the personal protective equipment (PPE) that workers currently must use.

                Proposed Label Clarification: Updated Respirator Statement

The Agency proposes to update the respirator statement currently on some tetraconazole labels. The proposed clarification does not fundamentally change the PPE that workers currently must use. The proposed change applies only to labels that already include respirator requirements; it does not affect tetraconazole product labels that do not now require respirators. 
		
 Proposed Label Clarification: Fungicide Resistance Management

Consistent with EPA's Pesticide Registration Notice on general pesticide resistance management, EPA is proposing pesticide resistance measures for existing chemicals during registration review and for new chemicals and new uses at the time of registration. To combat pesticide resistance, resistance management experts recommend using pesticides with different chemical modes (or mechanisms) of action against the same target pest population as part of IPM programs. This approach may prevent or delay target pest populations from developing resistance to a particular mode (or mechanism) of action without resorting to increased rates and frequency of application, possibly prolonging the useful life of pesticides.  

 Proposed Label Clarification: Minimum Retreatment Interval for Soybeans

The Agency is proposing updates to the directions for use on soybeans currently on tetraconazole labels to ensure clarity and consistency. Most products containing tetraconazole that are registered for use on soybeans currently allow a maximum of two applications/year. On some labels, the directions for use to treat Asian soybean rust currently suggest growth stages when these applications should be made but does not specify a minimum retreatment interval. EPA is proposing that these directions for use establish a maximum of two applications/year and a minimum 7-day retreatment interval for this use pattern. This proposal promotes consistency between labels. For the 2020 ecological risk assessment, the Agency assumed a 7-day retreatment interval. While a 7-day interval appears consistent with current use directions, the Agency is soliciting comments from stakeholders, particularly those who are familiar with how soybeans are grown, about whether or not a 7-day minimum retreatment interval between the two treatments is adequate to maintain efficacy. The Agency is also soliciting comments from stakeholders on the compatibility of a minimum 7-day retreatment with the need for rotation of different fungicidal chemistries employed to combat fungicide resistance. 

                7.  Proposed Label Clarification: Crop Group 8-10

The Agency notes that some product labels list use sites for crop group 9 and crop group 8-10. A tolerance has been established for crop group 8-10.  EPA is proposing labels be updated to identify only crop group 8-10.

      B.	Environmental Justice

EPA seeks to achieve environmental justice, the fair treatment and meaningful involvement of all people, regardless of race, color, national origin, or income, in the development, implementation, and enforcement of environmental laws, regulations, and policies. EPA has assessed risks to farmworkers who handle tetraconazole or may be exposed to tetraconazole when working in treated fields and has identified no risks of concern. EPA has also evaluated the risks to people living adjacent to treated fields, which may include farmworker families, and has also found no risks of concern for exposure to tetraconazole. The Agency seeks information on any other groups or segments of the population who, as a result of their location, cultural practices, or other factors, may have atypical, unusually high exposure to tetraconazole compared to the general population or who may otherwise be disproportionately affected by the use of tetraconazole as a pesticide.

 Tolerance Actions	

The Agency plans to exercise its FFDCA authority to modify the tolerances for tetraconazole to reflect Organization for Economic Cooperation and Development (OECD) rounding class practices and to correct commodity definitions as previously stated.  Refer to Section III.A.3 for details. The Agency will use its FFDCA rulemaking authority to make the necessary changes to the tolerances in a separate process that allows for public comment.   
 
 Proposed Interim Registration Review Decision  

The Agency is issuing this PID in accordance with 40 C.F.R. §§155.56 and 155.58. The Agency has made the following proposed interim decision: 1) outstanding data are still needed for tetraconazole, and 2) and tetraconazole does not meet the registration standard without the changes to the affected registrations and their labeling proposed in this document (See Section IV and Appendices A and B).

The Agency conducted detailed human health and ecological risk assessments. In these risk assessments, EPA observed risks associated with the continued registration of tetraconazole. The Agency determined that there are no human health risks of concern, including any dietary or residential risks of concern. As discussed in Section III of this document, potential chronic ecological risks of concern were identified primarily to mammals and birds. 

EPA also determined that the continued registration of tetraconazole provides benefits.  Tetraconazole has systemic properties that make it effective in preventing fungal infections and suppressing disease development in plants. Growers use tetraconazole to preserve crop yields and quality.   

Considering the potential ecological risks and the benefits associated with the use of tetraconazole, the Agency is proposing revisions to product labels to add advisory spray drift management language and clarifications that include updating the surface water advisory statement.  

During registration review, EPA considers whether a pesticide registration "continues to satisfy the FIFRA standard for registration." Here, EPA proposes that tetraconazole does not meet the FIFRA registration standard without the changes to the affected registrations and their labeling described in Section IV. and Appendices A and B. While there are potential ecological risks associated with the use of the compound, they can be mitigated with limited label changes while still preserving the benefits.

Taking into consideration the available information on toxicity and exposure, EPA assessed the potential aggregate risks, including dietary (food and water) and non-occupational residential exposures, and found no risks exceeding the Agency's levels of concern. EPA proposes that, per the requirements of the FFDCA, there is a reasonable certainty that no harm will result from aggregate exposure to tetraconazole, including all anticipated dietary exposures and all other exposures for which there is reliable information. Therefore, tetraconazole's residues do not present human dietary risk and EPA intends to make minor changes to the established tolerances because EPA's analysis indicates that those tolerances are safe.   

 Data Requirements 

A Generic Data Call-In (GDCI-120603-1573) for tetraconazole was issued for data needed to conduct the registration review risk assessments. Most of the data requirements from the DCI are satisfied. As noted in this document, additional pollinator data are still needed. The Agency intends to work with the registrants to help create a plan for developing the outstanding data. 
   
V. 	NEXT STEPS AND TIMELINE  
    
 Proposed Interim Registration Review Decision 
    
A Federal Register Notice will announce the availability of this PID for tetraconazole and open a 60-day public comment period. The Agency may issue an Interim Registration Review Decision (ID) for tetraconazole after the close of this comment period if there are no significant comments or additional information submitted to the docket during the comment period that leads the Agency to change the proposed interim decision explained in Section IV.C, above. EPA may issue an interim registration review decision for tetraconazole. The Agency may make a final registration review decision for tetraconazole without the Agency having previously issuing an ID. However, a final registration review for tetraconazole registration review case will only be made after EPA completes 1) a listed species determination and any needed consultation with the Services, and 2) an EDSP determination.

 Implementation of Mitigation Measures   

Once the Interim Registration Review Decision is issued, the tetraconazole registrants must submit amended labels that include the label changes described in Appendices A and B as well as the corresponding requests for amendment within 60 days. 

   
   
   
   
   
   

                                                                               
Appendix A:  Summary of Proposed Actions for Tetraconazole 
Registration Review Case # 7043
PC Code: 120603
Chemical Type: fungicide
Chemical Family: triazole 
Mechanism of Action:  disrupts fungal cell membrane permeability
Affected Population(s)
Source of Exposure
Route of Exposure
   Duration of Exposure
Potential Risks of Concern
Proposed Actions
Mammals
 Residues on food items
 Aerial and ground spray drift
 Consumption of aquatic animals

 Ingestion 

 Chronic
 Increased mortality
 Increased gestation time
 Advisory spray drift language
 Advisory surface water language

Birds

 Acute
 Chronic
 Weight reduction
 Mortality of young
   
Honey bees (pollinators/
terrestrial invertebrates)
 Residues in pollen and nectar
 Spray drift
Ingestion
 Chronic
 Decreased food consumption
 Advisory spray drift language

Appendix B:  Proposed Labeling Changes for Tetraconazole Products
                                  Description
          Proposed Label Language for TETRACONAZOLE End-Use Products
                              Placement on Label
Mode of Action Group Number

Note to registrant:
    Include the name of the ACTIVE INGREDIENT in the first column
    Include the word "GROUP" in the second column
       Include the MODE/MECHANISM OF ACTION CODE in the third column (for herbicides this is the Mechanism of Action, for fungicides this is the FRAC Code, and for insecticides this is the Primary Site of Action) 
    Include the type of pesticide (FUNGICIDE) in the fourth column. 
                                       
                                 TETRACONAZOLE
                                     GROUP
                                       3
                                   FUNGICIDE
                                       
Front Panel, upper right quadrant.
All text should be black, bold face and all caps on a white background, except the mode of action code, which should be white, bold face and all caps on a black background; all text and columns should be surrounded by a black rectangle.
Resistance-management for fungicides 
Include resistance management label language for fungicides/bactericides from PRN 2017-1 (https://www.epa.gov/pesticide-registration/pesticide-registration-notices-year)

Directions for Use, prior to directions for specific crops
Surface Water Advisory 
"This product may impact surface water quality through spray and runoff of rainwater. This product has a high potential for runoff for several months or more after application. Poorly draining soils or soils with shallow water tables are more prone to produce runoff that contains this product. A level, well-maintained vegetative buffer strip between areas to which this product is applied and surface water features such as ponds, streams, and springs will reduce the potential for contamination of water from rainfall runoff. Runoff of this product will be reduced by avoiding applications when rainfall is forecast to occur within 48 hours. Sound erosion control practices will reduce this product's contribution to surface water contamination."
Directions for Use
Updated Gloves Statement for labels already requiring the use of gloves
Update the gloves statements to be consistent with Chapter 10 of the Label Review Manual.  In particular, remove reference to specific categories in EPA's chemical-resistance category selection chart and list the appropriate chemical-resistant glove types to use. 
In Personal Protective Equipment (PPE) within the Precautionary Statements 
Updated Respirator Language for labels already requiring the use of a respirator

   [Note to registrant: If your end-use product only requires protection from particulates (low volatility), use the following language:]
   
   "Wear a minimum of a NIOSH-approved particulate filtering facepiece respirator with any N*, R or P filter; OR a NIOSH-approved elastomeric particulate respirator with any N*, R or P filter; OR a NIOSH-approved powered air purifying respirator with HE filters." 
   
   *Drop the "N" option if there is oil in the product's formulation and/or the product is labeled for mixing with oil-containing products. 
   
   [Note to registrant: For respiratory protection from organic vapor and particulates (or aerosols), use the following language:]
   
   "Wear a minimum of a NIOSH-approved elastomeric half mask respirator with organic vapor (OV) cartridges and combination N*, R, or P filters; OR a NIOSH-approved gas mask with OV canisters; OR a NIOSH-approved powered air purifying respirator with OV cartridges and combination HE filters." 
   
   [Note to registrant: For products requiring protection for organic vapor only, use the following language:] 
   
   "Wear a minimum of a NIOSH-approved elastomeric half mask respirator with organic vapor (OV) cartridges; OR a NIOSH approved full face respirator with OV cartridges; OR a gas mask with OV canisters; OR a powered air purifying respirator with OV cartridges."  
   
*Drop the "N" option if there is oil in the product's formulation and/or the product is labeled for mixing with oil-containing products.
In PPE within the Precautionary Statements
Advisory Spray Drift Management Language for all products delivered via liquid spray application
"SPRAY DRIFT ADVISORIES
THE APPLICATOR IS RESPONSIBLE FOR AVOIDING OFF-SITE SPRAY DRIFT.
BE AWARE OF NEARBY NON-TARGET SITES AND ENVIRONMENTAL CONDITIONS.

IMPORTANCE OF DROPLET SIZE
An effective way to reduce spray drift is to apply large droplets. Use the largest droplets that provide target pest control. While applying larger droplets will reduce spray drift, the potential for drift will be greater if applications are made improperly or under unfavorable environmental conditions.

Controlling Droplet Size  -  Ground Boom (note to registrants: remove if ground boom is prohibited on product labels)
:: Volume - Increasing the spray volume so that larger droplets are produced will reduce spray drift. Use the highest practical spray volume for the application.  If a greater spray volume is needed, consider using a nozzle with a higher flow rate.
:: Pressure - Use the lowest spray pressure recommended for the nozzle to produce the target spray volume and droplet size.
:: Spray Nozzle - Use a spray nozzle that is designed for the intended application. Consider using nozzles designed to reduce drift.

Controlling Droplet Size  -  Aircraft (note to registrants: remove if aerial application is prohibited on product labels)
:: Adjust Nozzles - Follow nozzle manufacturers' recommendations for setting up nozzles.  Generally, to reduce fine droplets, nozzles should be oriented parallel with the airflow in flight.

BOOM HEIGHT  -  Ground Boom (note to registrants: remove if ground boom is prohibited on product labels)
For ground equipment, the boom should remain level with the crop and have minimal bounce.

RELEASE HEIGHT - Aircraft (note to registrants: remove if aerial application is prohibited on product labels)
Higher release heights increase the potential for spray drift.  

SHIELDED SPRAYERS
Shielding the boom or individual nozzles can reduce spray drift.  Consider using shielded sprayers.  Verify that the shields are not interfering with the uniform deposition of the spray on the target area.

TEMPERATURE AND HUMIDITY
When making applications in hot and dry conditions, use larger droplets to reduce effects of evaporation.

TEMPERATURE INVERSIONS
Drift potential is high during a temperature inversion. Temperature inversions are characterized by increasing temperature with altitude and are common on nights with limited cloud cover and light to no wind. The presence of an inversion can be indicated by ground fog or by the movement of smoke from a ground source or an aircraft smoke generator. Smoke that layers and moves laterally in a concentrated cloud (under low wind conditions) indicates an inversion, while smoke that moves upward and rapidly dissipates indicates good vertical air mixing. Avoid applications during temperature inversions. 

WIND
Drift potential generally increases with wind speed. AVOID APPLICATIONS DURING GUSTY WIND CONDITIONS. Applicators need to be familiar with local wind patterns and terrain that could affect spray drift."
Directions for Use, just below the Spray Drift box, under the heading "Spray Drift Advisories"
Advisory Spray Drift Language for products that allow boomless ground sprayer application
"SPRAY DRIFT ADVISORIES
Boomless Ground Applications: 
Setting nozzles at the lowest effective height will help to reduce the potential for spray drift."
Directions for Use, just below the Spray Drift box, under the heading "Spray Drift Advisories"
Advisory Spray Drift Language for products that are applied with handheld equipment
"SPRAY DRIFT ADVISORIES
Handheld Technology Applications: 
--------------------------------------------------------------------------------
   Take precautions to minimize spray drift."

Directions for Use, just below the Spray Drift box, under the heading "Spray Drift Advisories"
Label Clarification for products registered for use on soybeans
 A maximum of two applications/year on soybean are permitted.
 Directions for use on soybeans must include a minimum 7-day retreatment interval for controlling or treating Asian soybean rust.  
Directions for Use
Label Clarification for products containing crop group 9
 Some product labels list use sites for crop group 9 and crop group 8-10. A tolerance has been established for crop group 8-10, so labels must be updated to identify only crop group 8-10.
Directions for Use

   Appendix C: Listed-Species Assessment 
In 2013, EPA, along with the Fish and Wildlife Service (FWS), the National Marine Fisheries Service (NMFS), and the United States Department of Agriculture (USDA) released a summary of their joint Interim Approaches for assessing risks to endangered and threatened (listed) species from pesticides. These Interim Approaches were developed jointly by the agencies in response to the National Academy of Sciences'(NAS) recommendations that discussed specific scientific and technical issues related to the development of pesticide risk assessments conducted on federally threatened and endangered species.   
  
Since that time, EPA has conducted biological evaluations (BEs) on three pilot chemicals representing the first nationwide pesticide consultations. These initial consultations were pilots and were envisioned to be the start of an iterative process. The agencies are continuing to work to improve the consultation process. For example, advancements to the initial pilot interim methods have been proposed based on experience conducting the first three pilot BEs. Public input on those proposed revisions is currently being considered.    
  
Also, a provision in the December 2018 Farm Bill included the establishment of a FIFRA Interagency Working Group to provide recommendations for improving the consultation process required under section 7 of the Endangered Species Act for pesticide registration and Registration Review and to increase opportunities for stakeholder input. This group includes representation from EPA, NMFS, FWS, USDA, and the Council on Environmental Quality (CEQ). Given this new law and that the first nationwide pesticide consultations were envisioned as pilots, the agencies are continuing to work collaboratively as consistent with the congressional intent of this new statutory provision. EPA has been tasked with a lead role on this group, and EPA hosted the first Principals Working Group meeting on June 6, 2019.    
  
Given that the agencies are continuing to develop and work toward implementation of approaches to assess the potential risks of pesticides to listed species and their designated critical habitat, the ecological risk assessment supporting this PID for tetraconazole does not contain a complete ESA analysis that includes effects determinations for specific listed species or designated critical habitat. Although EPA has not yet completed effects determinations for specific species or habitats, for this PID, EPA's evaluation assumed, for all taxa of non-target wildlife and plants, that listed species and designated critical habitats may be present in the vicinity of the application of tetraconazole. This will allow EPA to focus its future evaluations on the types of species where the potential for effects exists once the scientific methods being developed by the agencies have been fully vetted. Once that occurs, these methods will be applied to subsequent analyses for tetraconazole as part of completing this registration review.  
 
 
  
   
 
 
   
   Appendix D: Endocrine Disruptor Screening Program 
As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse outcomes from exposure to chemicals. Collectively, these studies include acute, sub-chronic and chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include endpoints which may be susceptible to endocrine influence, including effects on endocrine target organ histopathology, organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess growth, developmental and reproductive effects in different taxonomic groups. As part of its most recent registration decision for tetraconazole, EPA reviewed these data and selected the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. However, as required by FFDCA § 408(p), tetraconazole is subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).   
  
EPA has developed the EDSP to determine whether certain substances (including pesticide active and other ingredients) may have an effect in humans or wildlife similar to an effect produced by a "naturally occurring estrogen, or other such endocrine effects as the Administrator may designate." The EDSP employs a two-tiered approach to making the statutorily required determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go through Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 testing is designed to identify any adverse endocrine-related effects caused by the substance and establish a dose-response relationship between the dose and the E, A, or T effect.   
  
Under FFDCA § 408(p), the Agency must screen all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. The Agency has reviewed all the assay data received for the List 1 chemicals and the conclusions of those reviews are available in the chemical-specific public dockets. A second list of chemicals identified for EDSP screening was published on June 14, 2013, and includes some pesticides scheduled for Registration Review and chemicals found in water. Neither of these lists should be construed as a list of known or likely endocrine disruptors. Tetraconazole is not on either list. For further information on the status of the EDSP, the policies and procedures, the lists of chemicals, future lists, the test guidelines, and the Tier 1 screening battery, please visit the EPA website.