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Kasugamycin Human Health Risk Assessment DP Barcode D433630 Kasugamycin Human Health Risk Assessment DP Barcode D433630 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, DC 20460 OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION MEMORANDUM DATE: 27 Septem her 2017 SUBJECT: Kasugamycin. Human Health Risk Assessment forthe Proposed Section 3 Registration of New Uses of the Antibiotic Fungicide on Cherry Subgroup 12-12A and Walnuts. DP Barcode: PC Code: 230001 D433630 Registration Number: Decision Number: 513997 66330-404 Regulatory Action: Petition Number: 6E8450 Section 3 Registration (Tolerance Petition) Risk Assessment Type: Single Chemical Aggregate Case Number: 7045 TXR Number: NA CAS Number: 6980-18-3 (19408-46-9, HCI salt) MRID Number: NA 40CF�{\1,_80.6�4 � FROM: Linnea J. Hansen, Biologis��sor cJvv" William T. Drew, Chemist � � Gerad Thornton, Environmental Protection Specialist��--­ Registration Action Branch II Health Effects Division (HED), 7509P THROUGH: Christina Swartz, Chief Risk Assessment Branch II Health EffectsDivision (HED), 7509P To: Hope Johnson and Fatima Sow, PM Team 21 Fungicide Branch (FB) Registration Division (RD), 7505P and Tamica Cain Minor Use and Emergency Response Branch (MUERB)/RD, 7505P Page 1 of 45 Kasugamycin Human Health Risk Assessment DP Barcode D433630 Table of Contents 1.0 Executive Summary ............................................................................................................ 4 2.0 HED Recommendations...................................................................................................... 6 2.1 Data Deficiencies ............................................................................................................. 6 2.2 Tolerance Considerations ................................................................................................. 6 2.2.1 Enforcement Analytical Method ............................................................................... 6 2.2.2 International Harmonization ..................................................................................... 7 2.2.3 Recommended Tolerances ........................................................................................ 7 2.2.4 Revisions to Petitioned-for Tolerances ..................................................................... 8 2.3 Label Recommendations .................................................................................................. 8 2.3.1 Recommendations from Residue Reviews ............................................................... 8 2.3.2 Recommendations from Non-Dietary Exposure Reviews ........................................ 8 3.1 Chemical Identity ............................................................................................................. 8 3.2 Physical/Chemical Properties ........................................................................................... 9 3.3 Pesticide Use Pattern ........................................................................................................ 9 3.4 Anticipated Exposure Pathways ..................................................................................... 10 3.5 Consideration of Environmental Justice ........................................................................ 10 4.0 Hazard Characterization and Dose-Response Assessment ............................................... 11 4.1 Toxicology Studies Available for Analysis ................................................................... 11 4.2 Absorption, Distribution, Metabolism, & Elimination (ADME) ................................... 11 4.2.1 Dermal Absorption.................................................................................................. 12 4.3 Toxicological Effects ..................................................................................................... 12 4.4 Safety Factor for Infants and Children (FQPA Safety Factor)....................................... 14 4.4.1 Completeness of the Toxicology Database ............................................................. 14 4.4.2 Evidence of Neurotoxicity ...................................................................................... 14 4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal ......... 14 4.4.4 Residual Uncertainty in the Exposure Database ..................................................... 14 4.5 Toxicity Endpoint and Point of Departure Selections .................................................... 15 4.5.1 Dose-Response Assessment .................................................................................... 15 4.5.2 .......... Summary of Points of Departure and Toxicity Endpoints Used in Human Risk Assessment ................................................................................................................................ 15 5.0 Dietary Exposure/Risk Characterization ........................................................................... 16 5.1 Metabolite/Degradate Residue Profile ........................................................................... 16 5.1.1 Residues of Concern: Summary of Residue Data and Rationale ........................... 16 5.2 Food Residue Profile ...................................................................................................... 18 5.3 Water Residue Profile .................................................................................................... 19 5.4 Dietary Risk Assessment ................................................................................................ 20 5.4.1 Description of Residue Data and Percent Crop Treated Used in Dietary Assessment ……………………………………………………………………………………..20 5.4.2 Chronic Dietary Risk Assessment .......................................................................... 20 6.0 Residential (Non-Occupational) Exposure/Risk Characterization ................................... 21 6.1 Spray Drift ...................................................................................................................... 21 7.0 Aggregate Exposure/Risk Characterization ...................................................................... 22 Page 2 of 45 Kasugamycin Human Health Risk Assessment DP Barcode D433630 8.0 Cumulative Exposure/Risk Characterization .................................................................... 22 9.0 Occupational Exposure/Risk Characterization ................................................................. 22 9.1 Short- and Intermediate-Term Handler Exposure and Risk ........................................... 23 9.2.1 Dermal Post-Application Risk ................................................................................ 25 9.2.2 Inhalation Post-Application Risk ............................................................................ 25 10.0 References ......................................................................................................................... 27 Appendix A. Toxicology Requirements and Profile..................................................................... 29 A.1 Toxicology Data Requirements ...................................................................................... 29 A.2 Toxicity Profiles for Kasugamycin ................................................................................ 31 Appendix B. Metabolism Summary Tables .................................................................................. 41 Appendix C. Physical/Chemical Properties Table ........................................................................ 43 Appendix D. International Maximum Residue Limit Status for Kasugamycin. .......................... 44 Appendix E. Review of Human Research ................................................................................ 45 Page 3 of 45 Kasugamycin Human Health Risk Assessment DP Barcode D433630 1.0 Executive Summary The Interregional Research Project Number 4 (IR-4) has submitted a petition for the registration and establishment of permanent Section 3 tolerances for residues of the aminoglycoside fungicide kasugamycin (3-O-[2-amino-4-[(carboxyimino-methyl)amino]-2,3,4,6-tetradeoxy-α-D- arabino -hexopyranosyl]-D-chiro -inositol; CAS #6980-18-3) in or on cherry subgroup 12-12A and walnuts. The Registrant, Arysta LifeScience North America LLC, is proposing to use the currently registered product Kasumin 2L (EPA Registration No. 66330-404), a 2% a.i. liquid formulation. The proposed application rate is 0.084 lb a.i./acre (maximum annual application rate 0.336 lb a.i./acre/year) using ground or aerial application methods. Kasugamycin is a low-use-rate, wide-spectrum aminoglycoside antibiotic fungicide produced from Streptomyces kasugaensis . Kasugamycin formulations are applied as foliar sprays in agriculture and horticulture. Kasugamycin has preventative, curative and systemic activity at low application rates and controls a range of phytopathogenic organisms in the proposed crops. In the United States, kasugamycin is currently registered for use on pome fruits group 11-10. The aminoglycoside antibiotic group which also includes streptomycin and gentamicin, inhibits bacterial protein synthesis by binding to the 30S subunit of the bacterial ribosome. Their penetration through the cell membrane of the bacterium depends partly on oxygen-dependent active transport by a polyamine carrier system that seems to be absent in mammalian systems. This risk assessment document does not address the potential impact of the pesticidal use of kasugamycin on antibiotic resistance. Tolerance levels as recommended within
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