Document ID: EPA-HQ-OPP-2008-0441-0005
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2008-06-25T04:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

OFFICE OF

PREVENTION, PESTICIDES AND

TOXIC SUBSTANCES

MEMORANDUM

Date:  June 2, 2008

SUBJECT:	Denatonium Saccharide (PC code 129045). Revised Human Health
Risk Scoping Document in Support of Registration Review.  DP Barcode
D352579.

FROM:	Yan Donovan, Risk Assessor

		Health Effects Division (7509P)

		Office of Pesticide Programs

THRU:	Ray Kent, Branch Chief

		Susan Hummel, Senior Scientist

		Reregistration Action Branch 4

		Health Effects Division (7509P)

		Office of Pesticide Programs

TO:	Joy Schnackenbeck

		Chemical Review Manager

		Special Review and Reregistration Division (7508P)

		Office of Pesticide Programs

Executive Summary

Health Effects Division’s (HED) denatonium saccharide scoping team has
revised the revised human health risk assessment status update issued on
May 8, 2008.  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.  Currently
there is only one active registered product (Ro-Pel).  No dietary,
residential, or aggregate risk assessment was conducted before.  The
Agency’s most recent documentation on denatonium saccharide was a memo
dated May 9, 1996, where it was concluded that acute oral, dermal, and
inhalation toxicities for the formulated product are all category IV. 
Denatonium saccharide is not an eye or skin irritant (Category IV).  It
is not a skin sensitizer.   No subchronic or chronic toxicity studies
are available.  Denatonium saccharide and denatonium benzoate (Bitrex)
both share the same cation: denatonium, which is a quaternary ammonium
cation.  No subchronic or chronic toxicity studies are available on
denatonium benzoate either.  Based on acute toxicity studies on the
denatonium benzoate salt, the acute oral LD50 is category III, the acute
inhalation LC50 is II, but the acute dermal LD50 study is unacceptable.

HED’s denatonium saccharide scoping team concludes that since this is
a non-food use chemical, it is not subject to FQPA, therefore, no
aggregate risk assessment is needed for the Registration Review of
denatonium saccharide.  However, depending on the outcome of the
Agency’s drinking water exposure assessment, a dietary assessment
(drinking water exposure only) may be needed.  An ORE assessment may be
needed if denatonium saccharide is shown to be dermally absorbed.  As
for the data requirements, HED’s scoping team concludes that a dermal
absorption study on the denatonium saccharide active ingredient is
needed to determine if there is potential dermal exposure to residential
handlers.  A 90-day oral on rodent may be needed to assess chronic
dietary (water only) risk to denatonium saccharide.

Introduction

HED has evaluated the status of the human health assessment for
denatonium saccharide to determine whether sufficient data are available
and whether a new or updated human health risk assessment is needed to
support Registration Review.  HED has considered the most recent risk
assessments for denatonium saccharide, HED databases, the OPPIN
database, and a Google online search during the process of this scoping.
 For a complete listing of the references, see Reference Section at the
end of this memo.  

Denatonium saccharide and denatonium benzoate (Bitrex) both share the
same cation: denatonium, which is a quaternary ammonium cation. 
Denatonium cation is the most bitter substance known to date - dilutions
of as little as 10 ppm are unbearably bitter to humans.  The salts are
often used as aversive agents to prevent accidental ingestion (Google
search-Wikipedia).   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.  Currently there is only one active registered product: Ro-Pel
Tree Squirrel, Vole, Dog, and Cat Repellent (EPA Reg. # 81117-1).   It
is a ready-to-use liquid formulation which contains 0.065% denatonium
saccharide and 0.035% thymol.  This scoping document is for the
denatonium saccharide active ingredient only.  All products containing
denatonium benzoate as an active ingredient have been cancelled.   

Hazard Identification/Toxicology

No subchronic or chronic toxicity studies are available for denatonium
saccharide.   Acute oral, dermal, and inhalation toxicities are category
IV for the product formulation.  Denatonium saccharide is not an eye or
skin irritant (Category IV).  It is not a skin sensitizer (Agency memo
of 05/09/1996, C. Glasgow).  No subchronic or chronic toxicity studies
are available on denatonium benzoate either.  Based on acute toxicity
studies on the benzoate active ingredient, the acute oral LD50 is
category III, the acute inhalation LC50 is II, but the acute dermal LD50
study is unacceptable (HED memo of 10/23/2007, E. Reaves, TXR Nos.
0054508).

A screening search on OPP’s incident data system (IDS) indicated that
no incident has been reported for denatonium saccharide.

Conclusions: The HED registration review scoping team determined that a
dermal absorption study is needed to determine potential dermal exposure
to residential handlers.  Depending on the outcome of the Agency’s
drinking water exposure assessment, a 90-day oral study on rodent may be
needed to assess chronic dietary (drinking water only) risk to
denatonium saccharide.

Exposures 

No dietary or residential exposure assessment was conducted previously.

Conclusions: There are no food uses for denatonium saccharide and
contamination of home grown produce from residential use of denatonium
saccharide is unlikely, so exposure from consumption of food is not
assessed.  Dietary exposure from drinking water is not known at this
time since the Environmental Fate and Effects Division (EFED) does not
have enough environmental fate data to make the determination yet. 
Depending on the outcome of EFED’s drinking water assessment, a
chronic dietary assessment for drinking water exposure only may be
needed.  HED does not believe that there is acute dietary risk of
concern, because denatonium saccharide is such a bitter compound that it
is unlikely that human will accidentally consume enough to cause any
acute toxic effects. 

Exposures to residential handlers during application can occur. 
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, especially dermal exposure. A residential
handler dermal assessment may be necessary if denatonium saccharide is
dermally absorbed.  HED does not believe that risk from inhalation
exposure will be of concern since this product is to be applied using
coarse spray or paint brush, and the % ai in the RTU liquid formulation
is very low (0.065%).

Aggregate 

No aggregate risk assessment was conducted previously.

Conclusions:  HED’s scoping team concluded that since this is a
non-food use chemical, therefore, it is not subject to FQPA.  No
aggregate risk assessment is needed.  

Occupational Exposure and Risk

No occupational risk assessment was conducted previously.

Conclusions: HED’s scoping team concludes that although there are
exposure scenarios to workers who apply the pesticide, no occupational
handler assessment is needed at this time, based on the low acute
toxicity of the formulation, the required personal protective equipment
stated on the product label, and the fact that no incidents have been
reported so far.

 						

Data Requirements

A dermal absorption study on the saccharide active ingredient is needed.

A 90-day oral study on rodent may be needed.



References

Bibliography for Denatonium saccharide and Denatonium benzoate (OPPIN
database);

Agency memo of 05/09/1996, C. Glasgow, “EPA File Symbol/EPA Reg. No.:
45735-2/RoPel Animal, Rodent and Bird Repellant”;

HED memo of 10/23/2007, E. Reaves, TXR Nos. 0054508, “RED-0350-26839:
Denatonium benzoate/Bitrex”.  D340792;

Google online search- Denatonium- Wikipedia;

Google on line search- Denatonium saccharide- ChemBlink.

DCI Table

Guideline Number: 870.7600

Study Title:  Dermal Penetration Study 

Rationale for Requiring the Data

The use pattern of this product results in potential dermal exposure to
handlers.  

Practical Utility of the Data

How will the data be used?

To determine how much, if any, the saccharide is absorbed through the
skin.

How could the data impact the Agency's future decision-making? 

The result of this data will affect whether or not EAP needs to do a
dermal exposure assessment for residential handlers.  If EPA does not
have this data, then 100% absorption will needed to be assumed, and a
repeated dose dermal study will be required to assess handler dermal
exposure.



Guideline Number: 870.3100

Study Title:  90-day Oral Study on Rodent 

Rationale for Requiring the Data

This study is required for non-food use pesticides if oral exposure
could occur.  The 90-day rat oral study is required for hazard
characterization (possibly endpoint selection) and dose-setting for the
chronic/carcinogenicity study (40 CRF parts 9 and 158, subpart F).  In
the case of denatonium saccharide, the scoping conclusions indicated
that there may be dietary exposure from drinking water; therefore, it is
recommended that a 90-day study be conducted to assess chronic dietary
risk.

Practical Utility of the Data

How will the data be used?

The results of this study will be used to characterize the hazard of
denatonium saccharide and serve as the base for chronic dietary endpoint
selection.  

How could the data impact the Agency's future decision-making? 

The result of this data may affect the Agency’s decision to continue
to grant the existing use of denatonium saccharide with or without risk
mitigations.  

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