UNITED ST ATES ENVIRONMENT AL PROTECTION AGENCY WASHINGTON D.C., 20460 OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION

MEMORANDUM DATE: September 19, 2015
SUBJECT: d-Limonene: PRD Response to Comments on Registration Review Preliminary Risk Assessment
Caitlin Newcamp, Chemical Review**Man ~r**  Thomas Moriarty, Team Leader**t---** FROM:
Risk Management and Implementation Branch 1 Pesticide Re-evaluation Division (7508P)

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THROUGH: Neil Anderson, Branch Chief

# /~**1~'-----__,** Risk Management and Implementation Branch 1 Pesticide Re-evaluation Division (7508P) TO: d-limonene Registration Review Docket Docket Number: EPA-HQ-OPP-2010-0673 www.regulations.govSUMMARY OF COMMENTS AND AGENCY RESPONSES During the 60-day public comment period on the d-limonene Preliminary Risk Assessment, which opened on 12/24114 and closed on 2/23/15, the Agency received five public comments. Comments were submitted by the Center for Biodiversity (CBD) and at least one member ofthe general public. Ofthe comments submitted by the general public, one (EPA-HQ-OPP-2010- 0673-0022) was with regard to the use ofd-limonene as an active ingredient in pet care products

. B. Hughes (EPA-HQ-OPP-2010-0673-0022) The commenterprovided information on incidents related to domestic animals, and commented that d-limonene should not be in products intended forpets.
EPA Response: In response to the comment from B. Hughes, the Agency conducted a review of its database (the Incident Database System) for adverse incidents related to domestic animals and limonene/d-limonene, see Limonene and d-Limonene: Review of Domestic Animal Incidents (S.Recore; Sep, 2015) in the docket EPA-HQ-OPP-2010-0673 accessible at www.regulations.gov.
The Agency 's review captured incidents from January 1, 2010 to July 9, 2015, during which time a total of231 incidents involving domestic animals and either limonene or d-limonene were identified. Domestic pet incident information is submitted to the Agency as aggregate exposure counts, so information beyond exposure severity and year ofthe incident is not provided. The 231 incidents were categorized as follows: 6% fatal , 4% major, 18% moderate, 71 % minor and 1% unspecified. Minor incidents are designated by the animal exhibiting symptoms that were minimally bothersome and resolved rapidly. The 231 incidents were associated with 10 different d-limonene products (i.e

. notjust pet care products but, insect sprays, agricultural products, etc. ). Only one ofthe products associated with the 231 incidents is labelled for direct application to a pet (2724-759, Holiday Flea and Tick Shampoo, containing 5% d-limonene active ingredient). In the Agency ' s analysis, this one product accounted for the majority ofoverall pet incidents (82%) as well as the majority offatal or major incidents (20 out of24).
To better understand the character ofthe incidents associated with the d-limonene pet shampoo product, the Agency contacted the registrant ofproduct 2724-7 5 9, Wellmark International. Narrative information (i.e. , more detailed information such as species, age, route ofexposure, etc.) regarding incidents with this product was provided by Wellmark International. This information indicated that many ofthe incidents (43%, n= l 18) involving product 2724-759 were associated with unintended exposure 

### (e.g., ocular or oral exposure) or use ofthe product in a manner inconsistent with the label (use on animal below permitted age, product left on animal for extended time period, etc.). Wellmark also provided the Agency with sales data for the subject product. When the sales data is compared with incident data, a low incident rate is suggested: 0.02% or 2 per 10,000 units sold. By acknowledging that each unit would likely be used multiple times, the incident rate would decrease even further.
Based on the available information, i.e. , the Agency ' s analysis and incident information from the registrant, the Agency notes that not all incidents involving d-limonene and domestic pets are attributed to the intended use ofthe pet shampoo containing d-limonene as the active ingredient.In addition, when considering the number ofincidents that may be associated with the use ofthe d-limonene pet shampoo product, and the volume ofproduct sold, the Agency does not believe there is a significant concern ofrisk to domestic pets from product 2724-759 at this time. However, given the inherent potential risk from the direct application ofan insecticidal pet product, the Agency reviewed the product label to identify measures to strengthen or clarify the product label in an attempt to reduce risk offuture incidents. As a result, Wellmark International indicated that it would include additional information that specifies the appropriate age and weight ofa cat or dog on which the subject product can be used.