### UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460

MEMORANDUM DATE: May 2, 2013 O FFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION

SUBJECT: Denatonium Saccharide : Qualitative Risk Assessment for Registration Review PC Code : 129045 Decision No.: 474113 Petit ion No.: Not App licab le (N/A) Risk Assessment Type: Qualitative TXRNo.: N/A MRID No.: N/A DP Barcode: 408419 Registration No.: N/A Regulatory Action: Registration Review Case No.: N/A CAS No.: 90823

- 38-4 40 CFR: N/A FROM: J ess ica Kidwell , Risk Assessor

# ~**~** RAB IV, Health Effect s Division {7so9P)

. THROUGH: Elissa Reaves, Ph.D., Branch Chief 

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## ~ RAB IV , Health Effects Division (7509P) TO: Andrea Mojica, RM60 RMIB4, Pesticide Re-Evaluation Division (7508P) Attached is the Hea lth Effect Division's (HED's) qualitative human health risk assessment for denatonium saccharide to support registration review. HED has not required additional mammalian toxicity data for denatonium saccharide and did not conduct a quantitative risk assessment for dietary , residential, occupational or aggregate risk.

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### 1 of6Executive Summary
HED has prepared a human health risk assessment to support registration review for denatonium saccharide. Because ofthe low potential for exposure, low toxicity, and low frequency and severity of incidents reported, the HED has determined that a qualitative risk assessment is appropriate for denatonium saccharide. Denatonium saccharide is registered as a repellent or feeding depressant to reduce chewing and biting damage to outdoor structures and surfaces by tree squirrels, dogs and cats. It also reduces consumption of seeds and b ulbs by tre e squirrels and voles. Currently there is only one active registered product, Ro-Pel. Acute toxicity data for denatonium saccharide are availab le. Acute oral, dermal, and inhalation toxicities for the formulated product are all category IV. Denatonium saccharide i s not an eye or skin irritant. It i s also not a skin sensitizer. No long term studies with denato nium saccharide are available or were required

. Since this is a non -food use chemical, no dietary (food and water) exposure i s expected and there is no need for an aggregate risk assessment. Although there are exposure scenarios relevant to both occupational and res idential hand lers who apply the pesticide, no occupational or residential assessments are needed at this time based on th e fo llowing: 1) the low acute to xicity of denatonium saccharide, 2) it is an aversive agent, 3) the low percentage of active ingredient (a.i.) in the product, 4) the relatively small area treated (targ eted , not broadcast), 5) the required personal protective equipment and recommended precautionary language stated on the product label , and 6) the low frequency and severity of incidents reported. Introduction
Denatonium saccharide is re gis tered as a repellent or feeding depressant to reduce chewing and biting damage t o outdoor structures and surfaces (such as bark of trees, fences, poles, decks, planters, siding, garbage cans, and furniture) by tree squirrels, dogs and cats. It also reduces consumption of seeds and bulbs by tree squirrels and voles. Currently there is only one active registered product: Ro

- Pel Tree Squirrel, Vole, Dog , and Cat Repellent (EPA Reg

. # 81117- 00001). It is a ready-to-use liquid formulation which contains 0 .065% denatonium saccharide and 0.035% thymo l. Currently, only 50 Kg per annum or less of d enatonium saccharide i s imported (Email correspondence from the regis trant, Roger B rown, MCB, LLC, to Andrea Mojica, EPA , 10/8/2012). Denatonium saccharide contains the cation, denatonium, which i s a quaternary ammonium cation

. Denatonium c ation is the most bitter chemical compound known, with dilutions of as little as 10 ppm bein g unbearably bitter to humans (Google search

- Wikipedia)

. The salts are often used as aversive agents to prevent accidental ingestion (US CPSC, 1992). An aversive agent is a substance added to a product with the intent of deterring or limiting its inges tio n (US CPSC, 1992). Denatonium saccharide has a bitterness threshold of0.01 ppm. The threshold i s the concentration detected by 50% of the adult human subjects tested (US CPSC, 1992).

Page 2 of6One gallon of this product will treat 1000 to 4000 square feet. The maximum single application rate to a single site is 5.42xl0" 3 lbs ai/1000 

## :ttl. A single application is made using a paint brush or sprayer. A second application may be made in 2

-7 days to improve effectiveness. T he product has an extremely bitter and unpleasant taste. App li cators and ot her handlers mu st wear rubber gloves and protective eyewear (safety glasses or gogg les). For the current action, a search of the open literature was conducted to identify any new toxicity studies since HED ' s 2008 memorandum: " Denatonium Saccharide (PC code 129045). Revised Human Health Risk Scoping Document in Support of Registration Review " (D352579, Y. Donovan, 6/2/2008). None were found to be critical such that a quantitative assessment would be required

. Hazard Identification and Dose Response Assessment Acute oral , dermal, and inhalation toxicities are Category IV for the product formulation Ro

-Pel (0.065% denatonium saccharide and 0.035% thymol). The product formulation is also not an eye or skin irritant or a skin sensitizer (Glasgow, 1996). The acute oral and acute dermal LD 5o s were both >5000 mglkg (toxicity category IV) for male and female Sprague-Dawley albino rats. No treatment-related effects were seen in these studies. All animals were normal and healthy during the 14-day observation period. The acute inhalation LC 5 o was >2.52 mg/L (Toxicity Category IV) for Sprague Dawley albino rats. In the acute inhalation study, effects were observed during the 4-hour who le bo dy inhalation exposure and included irregular respiration, hunched posture and h ypoactivity. However, al l effects subsided upon exposure completion and all animals appeared normal and healthy during the 14-day observation period. No subchronic or chronic studies with denatonium saccharide are avai lab le. Limited chronic data from California EPA ' s Department of Pesticide Regulation on denatonium saccharide reported no adverse effects at doses up to 16 mg/kg/day in chronic rat or monkey studies using denatonium benzoate, which shares the same denatonium cation with denatonium saccharide. However, considering that oral consumption of significant amounts of denatonium saccharide is extremely unlikely due to its extreme bitterness, there is no concern for its potential acute o r chronic toxicity

. Based on the low frequency (2 cases from accidental exposure) and severity (low and moderate severity, including respiratory , ocular and/or gastrointestinal irritation) of incident cases reported for denatonium saccharide in both OP P Incident Data System (IDS) and the Centers for Disease Control and Prevention/National Institute for Occupational Safety and Health (CDC/NIOSH) Sentinel Event Notification System for Occupational Risk-Pesticides (SENSOR) databases, there does not appear to be a concern at this time that would warrant further investigation. The Agency will continue to monitor the incident information and if a co ncern is triggered, additional analysis w ill b e conducted (D41 091 0)

. The toxicology database for denatonium saccharide is adequate for registration review. No toxicological endpoints of concern have been identified for risk assessment. Although the 2008 scoping document had previously recommended a dermal absorption study and a 90-day oral toxicity rodent study, no additional mammalian toxicity studies are currently required for denatonium saccharide based on its low toxicity, its use as an aversive agent, the low percentage Page 3 of6a.i. in the product, the relatively small area treated (targeted, not broadcast), the required personal protective equipment and recommended precautionary language stated on the product label, and the low frequency and severity of reported incidents. HED believes a reduced set of data requirements is appropriate for this chemical. Dietary Exposures There are no food uses for denatonium saccharide, so exposure from consumption of food is not assessed. Based on the use pattern and the compound's extreme bitterness, dietary exposure from food and drinking water is unlikely to occur. In addition , HED has not identified any toxicolo gical points of departure needed to conduct a quantitati ve human health risk assessment. Therefore, no dietary assessments are needed. Occupational and Residential Exposures Exposures to occupational and residential handlers can occur during application, however, postapplication exposure is expected to be negligible due to the limited area of use. Denatonium saccharide is a ready-to-use liquid formulation which can be applied using paintbrush or sprayer. Dermal and inhalation exposures can occur during application. However, HED does not believe that risk from inhalation or dermal exposure will be of concern based on the following: 1) the product is to be applied using a coarse spray or paint brush, 2) the% a.i. in the RTU liquid formulation is very low (0.065%), 3) the relatively small area treated (targeted, not broadcast), 4) the required personal protective equipment and precautionary language is stated on the product label, 5) the compound has lo w acute toxicity and HED has not identified any toxicological endpoints to conduct a human health risk assessment, and 6) few incidents have been reported so far. Exposures and health risks to people using the currently registered product are expected to be rela tively low, therefore, residential and occupational assessments (dermal and inhalation) are not needed. Data Requirements None. Conclusions Due to the low potential for exposure, low toxicity, and low frequency and sever ity of incidents reported, the HED has determined that a qualitative risk assessment is appropriate for denatonium saccharide. Since this is a non-food use chemical, no dietary expos ure is expected and there is no need for an aggregate risk assessment. B ased on the use pattern and the compound's ex treme bitterness, dietary exposure from food and drinking water is unlikely t o occur. In addition, HED has not identified any toxicological points of departure needed to conduct a quantitative human health risk assessment. Therefore , no dietary assessments are needed.

Page 4 of6References California EPA. 2000. Summary ofToxicology Data Denatonium Saccharide. California Environmental Protection Agency, Department of Pesticide Regulation, Medical Toxicology Branch. Chemical Code #00398 1 , Tolerance # 52048. March 30 ,2000. Donovan, Y. 2008. Denatonium Saccharide (PC code 129045). Revised Human Health Risk Scoping Document in Support ofRegistration Review. DP Barcode D 352579. June 2, 2008. Glasgow, C. Agency memo of05 / 0911996, " EPA File Symbol/EPA Reg. No.: 45735-2/RoPel Animal, Rodent and Bird Repellant". D2212 90. Google online search- Denatonium Saccharide: Wikipedia. 2013.
Recore, S. 2013. Denatonium Saccharide: Review of Human Incidents. D410910. April16, 2013.
U .S. Consumer Product Safety Conunission (US CPSC). Final Report Study of Aversive Agents. 11/18/1992.

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### 6 of6Exposures to occupational and residential handlers can occur during application, however, postapplication exposure is expected to be negligible due to the limited area of use. Denatonium saccharide is a ready-to-use liquid formulation which can be applied using paintbrush or sprayer. Dermal and inhalation exposures can occur during application. However, HED does not believe that risk from inhalation or dermal exposure will be of concern because the product is to be applied using a coarse spray or paint brush and the percentage of active ingredient in the RTU liquid formulation is very low (0.065%). In addition, the area to be treated is small (targeted, not a broadcast use) and the required personal protective equipment and precautionary language stated on the product label limits the exposure potential. Also, the compound has low acute toxicity and HED has not identified any toxicological endpoints to conduct a human health risk assessment. Few incidents have been reported so far. Exposures and health risks to people using the currently registered product are expected to be relatively low, therefore, residential and occupational assessments (dermal and inhalation) are not needed.

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