UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460 OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION MEMORANDUM DAT E: March 16, 2016 SUBJECT: Difen acoum. Revised Human Health Assessment Scoping Document in Support of Registration Review. PC Code: I 1990 l DP Barcode: 0 432291 Decision No.: ..f/>070 Registration No.: NA Petition No.: NA Regulatory Action: Registration Review Risk Assessment Type: Single ChemicaVe Case No.: 7630 TXRNo.: NA CAS No.: 56073-07-5 MRID No.: NA 40 CFR: NA FROM: Margarita C. ollantes, M. S., Biologist · ~ -~?~i/t-· !°d'fc»iL!:z..-.• Jaime D" Agostino, Ph.D., Toxicologist ~ Risk Assessment Branch II (RAB2) Health Effects Division (7509P) THROUGH: Christina Swartz, Branch Chief c:S:l~-- Risk Assessment Branch II (RAB2) \ ~ Jess Rowland, Deputy Division Director <:]---::;;. ~ Jeff Dawson, Acting Deputy Division Director Health Effects Division (7509P) Office of Pesticide Programs T O: Ricardo Jones, Chemical Review Manager Risk Management and Implementation Branch I (RMIB l ) Pesticide Reevaluation Division (PRO) (7508P) As part of Registration Review, the Pesticide Reevaluation Di vision (PRO) has requested that the Health Effects Division (HED) provide a human health risk assessment scoping document for the rodenticide agent difenacoum to support Registration Review. This document was revised to include the correct date of the Hazard Assessment and Science Policy Council (HASPOC) decision memo as well as the current methodology used to determine the dermal absorption for cl ifenacoum. The most recent risk assessment fo r difenacoum was conducted in July, 20, 2007 (K. Schumacher, 0 330185). Page I of24 Executive Summary HED has prepared a scoping document to support Registration Review for di fenacoum (3-(3- biphenyl-4-yl-1,2,3,4-tetrahydro-1-naphthy l)-4-hydroxycoumarin). Difenacoum is a second generation anticoagulant rodenticide. Di fenacoum is registered to control house mice, a variety of rats as well as subterranean control of rats and voles in burrows inside and within 50 to 100 feet of agricultural buildings, man-made agricultural structures, residential homes, processing facilities, industrial and commercial buildings, trash receptacles, public buildings, transport vehicles (ships, trains and aircraft), docks, ports and terminal buildings. There are currently six difenacoum end-use products comprised of 0.005 % active ingredient (ai) and formulated as pellets, blocks, and ready-to-use place packs. Second-generation anti-coagulant rodenticides, consumer-use products (i.e., products '.S I lb) containing difethialone are prohibited. Professional/ commercial uses of second-generation anticoagulants, require bait stations for all outdoors and above-ground placements and/or indoor placements where children, wildlife or domestic animals may be exposed. Furthermore, commercial labels prohibit broadcast application of pellet baits. Products that are intended primarily for use in and around agricultural structures are packaged in ind ividual containers holding no less than 8 pounds (lbs) of bait. Products intended for commercial/professional use are packaged in individual containers holding no less than 16 pounds (lbs) of bait. Difenacoum is a racemic mi xture; both the cis- and trans- isomers are pesticidally active. To evaluate the scope of work necessary to support Registration Review, HED has considered recent risk assessments for difenacoum, updates to its toxicity, exposure, and usage databases, and the latest Agency science policy and risk assessment methodologies. The toxicology database for difenacoum is considered adequate for risk assessment except fo r the lack of an inhalation and a dermal study (0057384, U. Habiba, 3/1 /20 16) which are required at this time. An alternative to conducting an inhalation study would be to add additional PPE (i.e., use of respirators) to registered labels which would address risks of concern resulting from inhalation exposures to a point where the margins of exposure (MO Es) based on the Hazard Assessment and Science Policy Council (HASPOC) screening criteria would no longer be of concern. Based on the low MOEs calculated for dermal exposure, label changes are not an option instead of conducting a dermal study. HED also determined that a 2-generation reproduction study, an acute neurotoxicity battery, a subchronic neurotoxicity battery, and an immunotoxicity study are not required for difenacoum (0057384, U. Habiba, 3/ 1/2016). During Registration Review, the Agency may update PODs and toxicological endpoints based on updated policies for endpoint selection. Difenacoum inhibits the regeneration of vitamin K, which decreases the synthesis of blood coagulation factors and can lead to hemon-haging and death. Evidence of these anticoagulant effects, consisting of clinical signs, effects on clotting time, hemorrhaging, and subsequent death were observed in all species tested in the available mammalian studies. Since difenacoum affects the synthesis of new clotting factors, rather than directly affecting the circulating factors, a latency period typically exists between the time of exposure and the time of effect that is dependent upon the half-lives of the circulating clotting factors. No other types of adverse effects were observed in the database. including neurotoxicity. immunotoxicity, or developmental effects. The acute Page 2 of24 toxicity of difenacoum is severe via the oral, dermal, and inhalation routes of exposure (Category I). Difenacoum is not an eye or dermal irritant, nor is it a dermal sensitizer. In the previous 2007 assessment dietary (food and drinking water) exposures were not quantified because of the limited use pattern (strictly non-food rodenticide use with no dietary exposure). A quantitative assessment was performed for commercial and residential exposure only. Therefore an aggregate risk assessment was not conducted. A short term (ST) dermal and inhalation occupational and commercial handler exposure assessment will be required during Registration Review based on the potential exposure to handlers (loaders, applicator, etc.) during the use of difenacoum. Applicator/handler exposure to products formulated as blocks, and ready-to-use placement packs is considered to be negligible. However, applicator/handler assessments will be conducted for the loose pellet formulation only. Occupational post-application exposure is not expected due to the expectation of no significant surface residue from solid formulation applications nor worker contact with surfaces containing residues in areas treated with difenacoum products. Consumer use products may not contain second generation anticoagulants. Therefore, residential applicator/handler exposure will not be assessed. Residential post-application exposure is not anticipated as products must be placed in tamper resistant packaging if used above ground or where children, may be exposed. There have been recent changes in occupational and commercial assessment assumptions since the previous assessments that will need to be incorporated during Registration Review along with any changes to reevaluate the points of departure, toxicity endpoints, and uncertainty factors used for risk assessment purposes. Exposure from spray drift and volatilization is not anticipated for the current difenacoum use pattern. Introduction Difenacoum (3-(3-biphenyl-4-yl-1,2,3,4-tetrahydro-1-naphthyl)-4-hydroxycoumarin) is a second generation rodent control agent registered for the control of house mice, a variety of rats as well subterranean burrows control of voles in and around agricultural , man-made agricultural structures, residential homes, processing facilities, industrial and commercial buildings, trash receptacles, public buildings, transport vehicles (ships, trains and aircraft), docks, ports and terminal buildings. It is a warfarin-like compound that acts as an anticoagulant and is formulated as paraffin pellets, bait ready-to-use place packs, and paraffin blocks. All products contain 0.005 percent active ingredient. The most recent human health risk assessment was finalized in July 2007 (K. Schumacher; D330185). In 2008, the Agency issued a risk mitigation decision for ten rodenticides, of which difenacoum was included. The mitigation decision set restrictions in order to minimize exposure to children, wildlife and domestic animals. The risk mitigation decision does not apply to rodenticide field (non-commensal rodents) uses or tracking powder products. However, it should be noted that difenacoum has no tracking powder end use products. A brief summary is below. The details of the RMD can be found in docket number EPA-HQ-OPP-2006-0955-0764 at www.regulations.gov. Page 3 of 24 Consumer-use products (≤ 1 lb.) Second-generation anticoagulants are prohibited as well as loose treated whole- grain/pellets/meal as a form for indoors and above ground outdoor uses. Professional-use products Must be sold in quantities of ≥ 4 lbs. (first-generation anticoagulants/non-anticoagulants), ≥ 8 lbs. (second-generation anticoagulants; agricultural building areas) and ≥ 16 lbs. (second generation anticoagulants; above ground outdoors) May not be offered for sale in consumer stores (hardware, grocery, etc.). Must also be placed within 100 feet of a structure (fence and perimeter baiting beyond 100’ of a man-made structure are prohibited) when used outdoors and above ground, see 50 foot Document Clarification Letter to Bell (03.20.12) (signed) in docket number EPA- HQ-OPP-2006-0955-0820 found at www.regulations.gov.