Page 1 of 8 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF
CHEMICAL SAFETY AND

POLUTION PREVENTION MEMORANDUM

Date: July 28, 2010

SUBJECT: Propiconazole: Section 18 Emergency Exemption for Pr opiconazole (Tilt® EPA Reg. No. 100- 617); for Use on Avocado Trees.

PC Code: 122101 DP Barcode: D380160

Decision No.: 436555 Registration No.: 100-617

Petition No.: N/A Regulatory Action: Section 18 Risk Assessment Type: Single Chemical Aggregate CAS No.: 3125

T XR No.: NA 40 CFR: 180.434

MRID No.: None

FROM: James S Miller, Environmental Scientist

Risk Assessment Branch IV Health Effects Division (7509P) Office of Pesticide Programs

THRU: Raymond Kent, Chief,

Risk Assessment Branch IV Health Effects Division (7509P) Office of Pesticide Programs

TO: Bonnie Cropp-Kohlligian, Risk Assessor

A. Conrath /B. Madden RM 05 Risk Integration, Minor Use, and Emergency Response Branch Registration Division (7505P) Office of Pesticide Programs

Introduction

In a memorandum dated June 17, 2010, the Florida Department of Agriculture and Consumer Services submitted a request for the use of (T ilt®) propiconazole, to manage Laurel Wilt (Raffaelea lauricola) on avocados. This action was requested due to the fact that the redbay ambrosia beetle (Xykebirusu plabra tus) is a non-native insect that was identified for the first time in the United States in Georgia in 2002. Laurel Wilt has a symbiotic relationship with the redbay

ambrosia beetle. In a combined effort between state and federal agencies, it has been determined that avocado trees are very susceptible to this disease and that there are no existing registered pesticides that can adequately protect avocados. In January of 2010, a redbay beetle wasPage 2 of 8 discovered near a main avocado production area in Miami-Dade County. Florida has approximately 7,500 acres of commercially grown avocados, most of which are grown in MiamiDade County.

Propiconazole, [[2-(2,4-dichlorophenyl)-4 -propyl-1,3-dioxolan-2-yl]methyl]-1 H -1,2,4-triazole is a systemic triazole fungicide with protective and curative action. Propiconazole is formulated as liquids (emulsifiable, solubl e, and flowable concentrates packaged as “mix-your-own” and “ready-to-use” (RTU) products) and wettable powders in wate r-soluble packets (WP/WSP). Application rates vary depending upon the appl ication equipment and crop or use-site. Currently, propiconazole is registered for use in a variety of occupational and residential sites. Occupational uses include conve ntional agricultural and comm ercial sites, as well as

antimicrobial uses. Residential use-sites in clude ornamentals (her baceous, woody, non-bearing fruit/nut trees), turf (lawn applications), and ga rden crops with applications being performed by both professionals a nd homeowners.

For the purpose of this registration action, th ree general application methods are being considered and assessed for the use propiconazole as an emulsifiable concentr ate (Tilt® EPA Reg. No. 100-617) on Avocado Trees. Soil Application, which is designed to be absorbed by the roots and distributed in the xylem throughout the tree, a tree dire cted application with a handgun focusing on applying the product to the bark surfaces of all ages of tr ee, and tree injection through the trunk of the tree and distributed in the xylem throughout the tree. As noted within, this document only a ddresses exposures and risks for commercial agricultural uses, residential, and antimicrobial uses will not be addressed.

1.0 Hazard Characterization

On February 13, 2003 the Health Effects Divisi on (HED) Hazard Identification Assessment Review Committee (HIARC) reassessed FQPA requirements (TXR 0052277) for propiconazole in response to questions posed by the Natural Resources Defense Council (NRDC). No new data have been reviewed and no changes were made to the toxicology endpoints previously selected for Propic onazole (TXR 0050439 & 0051703). In October, 2005, the registrant conducted an ACN st udy (MRID 46604601) with propiconazole and submitted it to the Agency. Evaluation of this ACN study demonstrated that severe clinical signs of toxicity were not accompanied by nerv ous tissue damage and neurobehavioral effects were minimal. The propiconazole risk assessm ent team concluded that the ACN study satisfies the data gap imposed by HIARC and the 3X factor for the data base unc ertainty factor (UF DB ) can be reduced to 1X. The rat acute study also serves as the basis for short-term dermal and

inhalation scenarios.Page 3 of 8 1.1 Acute Toxicological Categories

Table 1: Propiconazole Acute Toxicity Profile

Guideline

No. Study Type MRID # Results Toxicity Category

870.1100 Acute Oral - rat 00058591 LD 50 =1517 mg/kg III

870.1200 Acute Dermal-rabbit 00058596 LD 50 = >4000 mg/kg III

870.1300 Acute Inhalation - rat 41594801 LC 50 = >50.84 mg/L IV

870.2400 Primary Eye Irritation 00058597 Corneal opacity reversed

in 72 hours III

870.2500 Primary Skin Irritation 00058598 No irritation IV

870.2800 Dermal Sensitization 44949501 Non sensitizer -

1.2 Toxicological Endpoints

Dermal Endpoints:

The short-term endpoint selected was based on ac ute clinical toxicity observed in the acute neurotoxicity study in rats (ACN) (MRID 46604601) discussed above. It was concluded that

the LOAEL for the clinical signs of toxicity in this ACN study was 100 mg/kg and the

NOAEL was 30 mg/kg. This endpoint is appropriate since the severe cl inical effects were

observed after administration of the test materi al within one day. Since an oral dose was selected, a 40% dermal absorption factor is used for route to r oute extrapolation.

Furthermore, due to the use pattern of this re gistration action, HED has determined that only a short-term assessment is appropriate, therefore and intermediate-, and long-term assessments

were not conducted.

Inhalation Endpoints:

The short-term inhalation toxico logical endpoint is 30 mg/kg/day based on an acute rat acute neurotoxicity study (MRID 46604601). An inhalati on absorption factor of 100% (default value assuming equivalent inhalation and oral absorption) will be used for route-to-route extrapolation. Since the short-term and in termediate-/long-term dermal and inhalation toxicological endpoints of con cern are the same, respectively for each duration, and based on oral studies, assessments of each exposure dura tion combines the dermal and inhalation doses and applies the appropriate route-specif ic absorption factor explained above.Page 4 of 8 However, due to the use pattern of this regi stration action, HED has determined that only a short-term assessment is appropriate, therefore and intermediate-, and long-term assessments

were not conducted.

The Agency’s level of concern for non-cancer risk s (i.e., target level for MOEs or Margins of Exposure) is defined by the uncerta inty factors that ar e applied to the assessment. The Agency applies a 10X factor to account for inter-species extrapolation a nd a 10X factor to account for intra-species sensitivity. The total uncertainty fa ctors that have been applied to non-cancer risk assessments are 100 for occupational, 100 for short- term residential and 100 for intermediate-, long-term residential scenarios (based on th e toxicology endpoint selection for General Population including in fants and children.

Propiconazole is listed as a Group C, Possible Human Carcinogen. A Q 1 * was not identified for propiconazole, therefore a quantitativ e cancer risk assessment is not required.

A margin of exposure (MOE) of 100 defines HE D’s level of concern (LOC) for commercial agricultural ( occupational ) exposures.

Table 2: Propiconazole Toxicological Endpoints

Exposure

Scenario Dose Used in Risk Assessment, UF Special FQPA SF* and

Level of Concern for Risk

Assessment Study and Toxicological

Effects

Short-Term (1-30 days)

Incidental Oral NOAEL= 30 mg ai/kg/day Residential MOE = 100 Occupational = NA Acute Neurotoxicity Study-Rats Clinical signs (piloerection, diarrhea, tiptoe gait).

Intermediate-Term (1 - 6 months)

Incidental Oral NOAEL= 10 mg ai/kg/day Residential MOE = 100 Occupational = NA 24 Month Oncogenicity Study -

Mice. Liver toxicity (increased liver weight in males and increase in

liver lesions (masses/raised areas/ swellings/nodular areas mainly)

Short-Term (1 - 30 days) Dermal (General Population, including infants and children) Oral Maternal NOAEL= 30 mg ai/kg/day Dermal absorption

(Rate = 40%) Residential MOE = 100 Occupational MOE = 100 Acute Neurotoxicity Study-Rats Clinical signs (piloerection, diarrhea, tiptoe gait).

Intermediate-Term

(1 - 6 months) and

Long-Term Dermal (>6 months) Oral NOAEL= 10 mg ai/kg/day Dermal absorption
(Rate = 40%) Residential MOE = 100 Occupational MOE = 100 24 Month Oncogenicity Study -

Mice. Liver toxicity (increased liver weight in males and increase in liver lesions (masses/raised areas/ swellings/nodular areas mainly)Page 5 of 8 Table 2: Propiconazole Toxicological Endpoints

Exposure

Scenario Dose Used in Risk Assessment, UF Special FQPA SF* and

Level of Concern for Risk

Assessment Study and Toxicological

Effects

Short-Term (1 - 30 days)

Inhalation Oral Dev. NOAEL=

30 mg/kg/day

Inhalation absorption (Rate = 100%) Residential MOE = 100 Occupational MOE = 100 Acute Neurotoxicity Study-Rats Clinical signs (piloerection, diarrhea, tiptoe gait

Intermediate-Term (1 - 6 months)

Long-Term Inhalation (>6 months) Oral NOAEL=

10 mg/kg/day Inhalation absorption

(Rate = 100%) Residential MOE = 100 Occupational MOE = 100 24 Month Oncogenicity Study -

Mice. Liver toxicity (increased liver weight in males and increase in liver lesions (masses/raised areas/ swellings/nodular areas mainly)

Cancer (Oral, dermal,

inhalation) Group C, possible human carcinogen, RfD approach for risk characterization.

2.0 Occupational Handler and Post-application Exposure and Risk

Occupational handler exposure is expected for certified applicat ors applying propiconazole to

avocado trees. Handler risks were assessed us ing a (Surrogate Exposures Guide) from the Pesticide Handlers Exposure Database (PHED). The occupational handler scenarios resulted in MOEs that do not exceed HED's level of concern (i.e., MOEs > 100) while adhering to label specific PPE directions, (i.e., Long Sleeve Shirt, Long Pants, Socks, Shoes, and Chemical Resistant Gloves).

Chemical-specific data were not submitted to the Agency in support of this Section 18 application, therefore it is HED policy to use data from the Pestic ide Handlers Exposure Database (PHED) Version 1.1 (Sur rogate Exposures Guide) to a ssess handler exposures in the absence of chemical specific data. According to the propiconazole label; (Tilt® EPA Reg. No. 100-617) relevant exposure scenarios for occupa tional handlers are (1) application via handgun sprayer, (2) application via tr ee injection, and (3) a pplication via soil drenching equipment (Groundboom). The unit exposure values provided in the PHED (Surrogate Exposures Guide) were used for exposure, dose and MOE (Margin of Exposur e), calculations.

The average adult weight of 60 kg was used for estimating dermal and inhalation exposure. Furthermore, the use patterns presented on the propos ed label are expected to result in short-term (1-30 days) exposure only. For all occupational handler s exposure scenarios, risks are below HED’s level of concern (i.e., MOEs are > 100) wi th label specific PPE and therefore not of

concern.Page 6 of 8 Label specific directions state that the Pers onal Protection Equipment (PPE) required for this action falls under category G, (long -sleeved shirt, long pants, chemical resistant gloves, shoes plus socks, and protective eyewear ). Furthermore the restricted entry interval (REI) is 12 hours, unless soil injected, which under th e WPS (worker protection Standa rds) allows workers to reenter treated areas if there will be no contact with treated materials.

Note: Based on the use pattern (soil directed/tre e bark) associated with the proposed Section 18 label, HED believes that post-application exposu re will be negligible . Therefore, a postapplication quantitative asse ssment was not conducted.

The resulting doses and MOEs are presented in Table 3.Page 7 of 8 Table 3: Short-Term Occupational Handl er Exposure and Risk for Propiconaz ole (Tilt® EPA Reg. No. 100-617)

Exposure

Scenario Crop App Rate (lb ai/A) a Acres

Treated

Daily Unit Exposure (mg/lb ai) b Dose (mg/kg/Day) Short-Term

MOEs

Dermal Long Sleeve Shirt, Long

Pants + Gloves Baseline

inhalation Dermal Long Sleeve Shirt, Long

Pants + Gloves Baseline

Inhalation Combined

MOE c

Open Mixer/Loader (Liquid)

1 Handgun Sprayer (PHED) Avocado

Trees 7.1 100 0.023 1.2 0.10886 0.0142 240

Applying (Liquid)

1 Handgun Sprayer (PHED) Avocado

Trees 7.1 5 0.34 1.4 0.08046 0.00008 370

Mixer/Loader/Applicator (Liquid)

2 Groundboom

Soil Drench

(PHED) Avocado

Trees 7.1 80 0.057 1.3 0.21584 0.01231 130

Applicator (Liquid)

2 Groundboom

Soil Drench

(PHED) Avocado

Trees 7.1 80 0.014 0.74 0.05301 0.00701 500

Applicator

Tree Injection Not Assessed: Handgun and Soil Drench are protective

1Handgun Sprayer (PHED) acrea tr eated based on HED directions: 100 Acres mixed = 20 workers x 5 Acres . (Individual worker mixes = 100 Acres / day)

2 Soil Drench calculations Groundboom: 80 Acres / day

. PHED SOP.009 a. Application rate based on proposed uses on the label for (Tilt® EPA Reg. No. 100-617) b. Unit Exposures based on PHED Version 1.1. Surrogate Exposures Guide.

C. Combined MOE = inhalation + DermalPage 8 of 8 3.0 Residential Handler and Post-application Exposure and Risk

Due to the nature of this regi stration action, a reside ntial handler and post- application assessment

were not conducted.

Spray Drift

Spray drift is always a potential source of expos ure to residents nearby to spraying operations. This is particularly the case with aerial appl ication, but, to a lesser ex tent, could also be a potential source of exposure from the ground ap plication method employed for propiconazole. The Agency has been working with the Spray Dr ift Task Force, EPA Regional Offices, and State Lead Agencies for pesticide regulation and ot her parties to develop the best spray drift management practices. The Agen cy is now requiring interim mitigation measures for aerial applications that must be placed on product la bels/labeling. The Agency has completed its evaluation of the new data base submitted by the Spray Drift Task Force, a membership of U.S. pesticide registrants, and is de veloping a policy on how to appr opriately apply the data and the AgDRIFT computer model to its risk assessments for pesticides applied by air, orchard airblast, and ground hydraulic methods. After the policy is in place, the Agency may impose further refinements in spray drift management practices to reduce off-target drift and risks associated with aerial as well as other application types wher e appropriate. Note that in this assessment, propiconazole is not dire ctly applied to resident ial turf and does not re sult in exposures of concern. It is unlikely that spray drift would result in a higher poten tial for risk of exposure than the scenarios already assessed.

4.0 Conclusion

For all occupational ap plication exposure scenarios, Ma rgins of Exposure (MOEs) were ≥ 100

and therefore risks were not observed at the enclosed application rate. Furthermore, Propiconazole is listed as a Group C, Possible Human Carcinogen. A Q 1 * was not identified for propiconazole, therefore a quantitativ e cancer risk assessment is not required.