


                                       
                                       
                                       
                                       
                                       



Registration Decision for New Active Ingredient of Potassium Salts of Hops Beta Acids



                                       



                                                                               
                                             Approved by: _____________________
                                                                               
                                           									Jack E. Housenger, Director
                                          									Office of Pesticide Programs
                                                                               
                                                   Date: ______________________
                                                                               
Background

On November 04, 2013, the U.S. Environmental Protection Agency ("EPA") received an application from Interregional Research Project Number 4 (IR-4), on behalf of BetaTec Hop Products, Inc., A Division of John I. Haas, Inc. for the registration of a new active ingredient Potassium Salts of Hops Beta Acids (K-HBAs). No Chemical Abstract Service (CAS) number is currently assigned to this chemical. There will be three new products sold under the trade names "HopGuard Technical Grade Active Ingredient (TGAI) (Potassium Beta Resin = KBR)," "HopGuard Liquid," and "HopGuard II."  K-HBA s are classified as biochemical pesticides based on their history of exposure to humans and the environment demonstrating minimal toxicity, being structurally-similar and functionally identical to a naturally-occurring active ingredient and their non-toxic mode of action to the target pest(s). It is derived from the resin components of the cones of female hop plants, Humulus lupulus.  There are three major components of Hop Beta Acids (HBAs):  lupulone (30-55% with an isopropyl side chain); colupulone (20-55% with an isobutyl side chain); and adlupulone (5-10% with a secbutyl side chain). There has been a history of use of the K-HBAs products.  In 2001, the EPA granted a Section 18 Emergency Exemption for use in over 20 States to control Varroa mites (Varroa destructor) in honeybee hives and it was renewed in 2012 and 2013 in up to 37 States for the same purpose. Further, in support of a Generally Recognized as Safe (GRAS) determination by U.S. Food and Drug Administration (FDA) (2001), the safety of all extracted acids of hops (including Hops Beta Acids) was supported by a long history of safe use in foods, especially beer, throughout recorded history. The literature review demonstrated that no information was available that was inconsistent with the safety determination for the proposed uses. 

K-HBAs are intended to be applied inside commercial bee hives to the brood supers (chambers) via plastic strips to control Varroa mites (Varroa destructor) on honey bees. BetaTec Hop Products Inc. has requested that 40 CFR part 180 be amended by establishing an exemption from the requirement of a tolerance for residues of the biochemical pesticide Potassium Salts of Hops Beta Acids in or on honey and honey comb when used for the control of Varroa mites in accordance with label directions and good agricultural practices. A copy of the petition is available in Docket ID EPA-HQ-OPP-2014-0374 via http://www.regulations.gov.
Evaluation

In evaluating a pesticide registration application, the EPA assesses a wide variety of environmental fate (i.e., how the chemical will move in the environment) and toxicity studies (i.e., effects on non-target organisms) to determine the likelihood of adverse effects (i.e., risk) from exposures associated with the proposed use of the product. Risk assessments are developed to evaluate the environmental fate of the compound as well as how it might affect a wide range of non-target organisms including humans, terrestrial and aquatic wildlife (plants and animals). On the basis of these assessments, EPA evaluates and approves language for each pesticide label to ensure the directions for use and safety measures are appropriate to mitigate any potential risk.   In this way, the pesticide's label helps to communicate essential limitations and mitigations that are necessary for public safety. In fact, the pesticide law has a provision which indicates that it is a violation to use a pesticide in a way that conflicts with the label.  

Assessment of Risk to Human Health

EPA requires a wide range of studies in order to assess a pesticide. For K-HBAs, the database of studies required to support the assessment of risk to human health is complete. 

K-HBAs are lowly toxic by the oral and inhalation routes of exposure (Toxicity III and IV, respectively). However, K-HBAs are corrosive to the eyes (Toxicity Category I) and therefore personal protective equipment (PPE) precautionary language statements are proposed to be placed on the label to mitigate eye irritation. The label precautionary signal word is "DANGER".  

The evaluation of the data and information submitted indicate that K-HBAs are not structurally-related to known mutagens, nor are they in a chemical class known to contain a known mutagen. EPA concludes that from the available toxicity studies, K-HBAs demonstrated no subchronic toxic effects. In addition, there are no known systemic effects of K-HBAs via oral, dermal, or inhalation routes of exposure. Furthermore, EPA has not found K-HBAs to share a common mechanism of toxicity with any other substances, and K-HBAs do not appear to produce a toxic metabolite produced by other substances.

Given the low likelihood of adverse effects on humans, more refined estimates of acute and chronic dietary risk were not necessary for K-HBAs. Humans are currently exposed to K-HBAs through its use as a preservative in meats and its presence in beer. Furthermore, human exposure to K-HBAs via dietary exposure to pesticide-treated commodities such as honey, is not expected. K-HBAs are formulated into a viscous liquid and coated on plastic strips which are placed inside the beehives. Residues on food commodities are not anticipated as the half-life of K-HBAs is estimated to be 36 hours. In addition, the chemical is non-volatile and is expected to degrade rapidly with 100% degradation. No significant exposure via drinking water is expected from K-HBAs use as an active ingredient as a pesticide as the product is not sprayed or applied in any way that it would be expected to contact any source of drinking water. 

For more information, please refer to the document entitled, "Science Review in support of the Registration of HopGuard TGAI, HopGuard Liquid, and HopGuard, a New Active Ingredient. Review of Residue Studies, Tier I Toxicity and Tier Non-Target Organism Studies and Rationales)," which can be found in Docket ID EPA-HQ-OPP-2014-0375.

 Assessment of Ecological Risk 

The battery of tests required to assess the environmental fate and ecological effects of K-HBAs is complete. Based on a lack of exposure, effects of K-HBAs on non-target organisms, including threatened and endangered species, are highly unlikely and not anticipated.  Runoff into ground and surface waters is not anticipated. The end-use product (plastic strips treated with a 16% solution of HBAs) is manually inserted into commercial beehives. Additionally, three years of residue studies using HBAs in beehives to control Varroa mites demonstrated that there were no adverse effects on bees It is highly unlikely that non-target insects will gain access to the treated strips inside the hive due to the vigorous defense of hives by the honey bees against invaders. Furthermore, it is highly unlikely that organisms external to the hive will have access to the treated strips, and little or no likelihood that the active ingredient will migrate from the hive to the external environment.  In the highly unlikely event that Hops Beta Acids would migrate out of the beehive to the external environment, environmental fate data indicate that Hops Beta Acids would degrade rapidly, with 100% degradation in 36 hours in the light and 4 days in the dark. 

For more information, please refer to the document entitled, "Science Review in support of the Registration of HopGuard TGAI, HopGuard Liquid, and HopGuard, a New Active Ingredient. Review of Residue Studies, Tier I Toxicity and Tier Non-Target Organism Studies and Rationales)," which can be found in Docket ID EPA-HQ-OPP-2014-0375.
Alternatives
The use of this biochemical miticide is expected to displace and reduce the amount of conventional active ingredients (Coumaphos, Fluvalinate, and Amitraz) required for this purpose. Growers may prefer to use K-HBAs as a viable alternative to conventional miticides because K-HBAs will have an established exemption from the requirement of a tolerance (no limitations) for use on honey and honeycomb, indicating that it is safe. Conventional miticides generally have tolerances and may result in residues of concern on honey and honeycomb.
Benefits and Public Comments

By definition alone, biochemicals are favorable when compared to currently registered conventional alternatives because biochemicals are naturally-occurring substances (or substances structurally-similar and functionally identical to naturally-occurring substances) with a history of exposure to humans and the environment demonstrating minimal toxicity and a non-toxic mode of action to the target pest(s). Benefits of biochemical pesticides as compared to conventional pesticides typically include lower toxicity profiles for humans and non-target organisms, and faster degradation in the environment. As outlined above, K-HBAs are a viable alternative to conventional miticides containing a low toxicity profile and half-life of less than four days.

On August 13, 2014, EPA published a Notice of Receipt in the Federal Register of three applications for registration of K-HBAs for new active ingredient for use in beehives to control Varroa mites (Varroa destructor) on honey bees and announced a public comment period of 30 days. No comments were received in response to this Notice of Receipt.

On September 16, 2014, EPA published a Notice of Filing in the Federal Register announcing the receipt of the initial filing of the K-HBAs petition by IR-4 on behalf of BetaTec Hop Products, Inc. A Division of John I. Haas, Inc., under the Federal Food, Drug and Cosmetic Act (FFDCA) requesting the establishment of an exemption from the requirement of a tolerance for residues of K-HBAs in or on honey and honeycomb, when used for the control of Varroa mites in accordance with label directions and good agricultural practices. This publication also announced a public comment period of 30 days. There were sixty-three comments received on the FFDCA Notice of Filing. All sixty three comments were in response to the batched notice of filing but none were specific to K-HBAs. The comments were specific to the other Notice of Filings (NOFs) listed in the batched Federal Register Notice (FR).
Regulatory Decision

The K-HBAs database is comprised of six studies and is considered to be complete. The proposed food use of K-HBAs is well supported by this database. In considering the assessed risk to human health and the environment, the Agency concludes that K-HBAs meet the regulatory standard under the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA). There are no outstanding data requirements for this biochemical. Therefore, the EPA is granting the unconditional registration of the K-HBAs as a new active ingredient food use under Section 3(c)(5) of FIFRA.  

Three products will be registered: HopGuard Technical Grade Active Ingredient (TGAI) (Potassium Beta Resin = KBR); HopGuard Liquid is a manufacturing-use product (MP); and HopGuard II is an end-use product (EP). Applications of the end - use product can be made during spring, summer, and fall. The application rate of the end-use product is one strip per 5 deep combs covered by bees in each super (chamber), which is equivalent to two strips per ten frame brood super (chamber). Further, the end-use product has a maximum application rate of three applications per year (6 strips or approximately 24 grams of potassium salts of Hops Beta Acids) per ten frame brood super (chamber). 

For more information, please refer to the document entitled, "Science Review in support of the Registration of HopGuard TGAI, HopGuard Liquid, and HopGuard, a New Active Ingredient. Review of Residue Studies, Tier I Toxicity and Tier Non-Target Organism Studies and Rationales)," which can be found in Docket ID EPA-HQ-OPP-2014-0375.

