UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF

PREVENTION, PESTICIDES AND

TOXIC SUBSTANCES

[MEMORANDUM]{.underline}

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 LD~50~ is category III, the
acute inhalation LC~50~ is II, but the acute dermal LD~50~ 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 LD~50~ is category
III, the acute inhalation LC~50~ is II, but the acute dermal LD~50~
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**

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

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

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

4)  Google online search- Denatonium- Wikipedia;

5)  Google on line search- Denatonium saccharide- ChemBlink.

> [DCI Table]{.underline}

+-----------------------------------------------------------------------+
| > **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.                                           |
+-----------------------------------------------------------------------+