UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

DATE: May 2, 2013 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

SUBJECT: Denatonium Saccharide: Qualitative Risk Assessment for Registration Review 

PC Code: 129045 

Decision No.: 4 74113 

Petition No.: Not Applicable (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

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TO: Andrea Mojica, RM60 

RMIB4, Pesticide Re-Evaluation Division (7508P) 

Attached is the Health 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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Executive Summary 

HED has prepared a human health risk assessment to support registration review for denatonium 

saccharide. Because of the 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 bulbs by tree squirrels and voles. Currently there is only one active 

registered product, Ro-Pel. 

Acute toxicity data for denatonium saccharide are available. Acute oral, dermal, and inhalation 

toxicities for the formulated product are all category IV. Denatonium saccharide is not an eye or 

skin irritant. It is also not a skin sensitizer. No long term studies with denatonium saccharide are 

available or were required. 

Since this is a non-food use chemical, no dietary (food and water) exposure is expected and there 

is no need for an aggregate risk assessment. Although there are exposure scenarios relevant to 

both occupational and residential handlers who apply the pesticide, no occupational or residential 

assessments are needed at this time based on the following: 1) the low acute toxicity 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 (targeted, 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 registered as a repellent or feeding depressant to reduce chewing and 

biting damage to 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% thymol. Currently, only 50 Kg per annum or less of denatonium saccharide is 

imported (Email correspondence from the registrant, Roger Brown, MCB, LLC, to Andrea 

Mojica, EPA, 10/8/2012). 

Denatonium saccharide contains the cation, denatonium, which is a quaternary ammonium 

cation. Denatonium cation is the most bitter chemical compound known, with dilutions of as 

little as 10 ppm being 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 ingestion (US 

CPSC, 1992). Denatonium saccharide has a bitterness threshold of0.01 ppm. The threshold is 

the concentration detected by 50% of the adult human subjects tested (US CPSC, 1992). 

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One 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. The product 

has an extremely bitter and unpleasant taste. Applicators and other handlers must wear rubber 

gloves and protective eyewear (safety glasses or goggles). 

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 LD5os 

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 LC5o 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 whole body inhalation exposure and included irregular respiration, 

hunched posture and hypoactivity. However, all 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 available. 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 or 

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 OPP 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 concern is triggered, additional 

analysis will be 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 of6 
a.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 

toxicological points of departure needed to conduct a quantitative 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 low 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 relatively 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 severity 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 exposure is expected 

and there is no need for an aggregate risk assessment. 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 toxicological points of departure needed to 

conduct a quantitative human health risk assessment. Therefore, no dietary assessments are 

needed. 

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References 

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 of Registration Review. DP Barcode D352579. June 2, 2008. 

Glasgow, C. Agency memo of05/0911996, "EPA File Symbol/EPA Reg. No.: 45735-2/RoPel 

Animal, Rodent and Bird Repellant". D221290. 

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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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 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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