**Chitin and Chitosan Summary Document**

**Registration Review: Initial Docket**

**September 2007**

**TABLE OF CONTENTS**

**Page \#**

I.  **Preliminary Work Plan (PWP) 3**

> Introduction 3
>
> Anticipated Risk Assessment and Data Needs 4
>
> Incidents 4
>
> Efficacy and Label Claims 4
>
> Timeline 5
>
> Guidance for Comments 5

## Next Steps 5

II. **Fact Sheet -- Chitin, Poly-N-Acetyl-D-Glucosamine 6**

> Background Information 6
>
> Description of the Active Ingredient 6
>
> Use Information 6
>
> Recent Actions 7
>
> Ecological Risk Assessment Status 7
>
> Human Health Risk Assessment Status 7
>
> Incidents 8

#### Labels and Products 8

III. **Fact Sheet - Chitosan, Poly-D-Glucosamine 9**

> Background Information 9
>
> Description of the Active Ingredient 9
>
> Use Information 10
>
> Recent Actions 10
>
> Ecological Risk Assessment Status 10
>
> Human Health Risk Assessment Status 11

###  Incidents 12

#### Labels and Products 12

**I. PRELIMINARY WORK PLAN**

**[Introduction:]{.underline}**

The Food Quality Protection Act of 1996 mandated the continuous review
of existing pesticides. All pesticides distributed or sold in the United
States must generally be registered by EPA, based on scientific data
showing that they will not cause unreasonable risks to human health,
workers, or the environment when used as directed on product labeling.
The new registration review program is intended to make sure that, as
the ability to assess risk evolves and as policies and practices change,
all registered pesticides continue to meet the statutory standard of no
unreasonable adverse effects. Changes in science, public policy, and
pesticide use practices will occur over time. Through the new
registration review program, the Agency periodically reevaluates
pesticides to make sure that as change occurs, products in the
marketplace can be used safely. Information on this program is provided
at: http://www.epa.gov/oppsrrd1/registration_review/.

The Agency has begun to implement the new Registration Review program
pursuant to FIFRA Section 3(g) and intends to review each registered
pesticide approximately every 15 years to determine whether it continues
to meet the FIFRA standard for registration. The public phase of
registration review begins when the initial docket is opened for each
case. The docket is the Agency's opportunity to state clearly what it
knows about the pesticide and what additional risk analyses and data or
information it believes are needed to make a registration review
decision. Chitin and Chitosan are among the first biochemical pesticides
to undergo the registration review process and to be reassessed using
the most current standards of risk assessment.

Because Chitosan is derived from Chitin, and because both compounds
share basic physical characteristics, they have been combined into a
single case - Registration Review Case 6063. As a matter of general
similarity, Chitin and Chitosan are both naturally occurring polymers
that are ubiquitous throughout nature. Structurally, they are related to
cellulose and each consists of long chains of glucose molecules.
Relationally, Chitosan is a deacetylated product of Chitin, whose chains
of glucose are slightly modified. As biochemical active ingredients,
they are applied in different use patterns; however, they both
demonstrate a low toxicity profile, and are both known for their role in
bolstering plant resistance. Based on these factors and the data
submitted, no adverse human health or ecological risks are expected as a
result of exposure to these compounds, if they are used as labeled.
However, if additional information is submitted that warrants further
risk assessment~~s~~, the Agency will then conduct any necessary risk
assessment(s). Further information regarding use sites, summaries of
health, ecological effects data reviews and endangered species
assessments, as well as a list of registered pesticide products
containing these active ingredients, is found in Parts II and III in
this document.

**[Anticipated Risk Assessment and Data Needs:]{.underline}**

***Ecological Risk Assessment:*** Ecological effects for both Chitin and
Chitosan were duly considered in the course of reviewing the
applications for the first products containing these active ingredients.
In each case, non-target data and/or various non-target waiver requests
were sufficient to determine that the proposed uses of the pesticides
containing these active ingredients posed negligible to non-existent
ecological risk. These determinations were captured in both summary
science memos and regulatory decision documents. EPA's ecological risk
assessments are undergirded by the understanding that both Chitin and
Chitosan are naturally occurring, ubiquitous, and regarded as
essentially non-toxic to animals. Additionally noteworthy, applications
of pesticides containing Chitin or Chitosan are not expected to result
in concentrations of the compounds measurably greater than common
background concentrations. Accordingly, the Agency anticipates that no
additional ecological effects or environmental data are required for
either Chitin or Chitosan.

*Endangered Species Act:* Endangered species assessments for Chitin and
Chitosan are expected to be completed in October of 2007. The assessment
documents will be added to the docket at that time. Potential commenters
will also have full opportunity to make comments during the 60 day
comment period when the assessment documents are posted in the docket
for the *Proposed Registration Review Decision for Chitin* .

***Human Health:*** Based on reviews of human health exposure and
summary risk assessments that were conducted when the first pesticides
containing these active ingredients were originally registered, the
Agency anticipates that no additional human health effects data will be
required for either Chitin or Chitosan. The reviews indicate that data
were sufficient to fulfill all current biochemical pesticide toxicology
data requirements for both Chitin and Chitosan. Moreover, all the data
reviewed by the Agency indicate that both Chitin and Chitosan are so low
in toxicity as to be considered virtually non-toxic to humans or
animals. In further support of Chitin's and Chitosan's lack of toxicity,
it is also noted that both ingredients are regularly present in many
foods; and both have an exemption from the requirement of a tolerance --
40 CFR 180.1089 and 40 CFR 180.1072, respectively. In sum, the Agency
anticipates that no new data or human health risk assessments will be
necessary for either Chitin or Chitosan.

**[Incidents:]{.underline}**

The OPP Incident Data System (IDS) indicates that there have been no
reports of human and domestic animal incidents for products containing
either Chitin or Chitosan. The Agency will consider any additional
incidents data or comments submitted in response to this docket.

**[Efficacy and Label Claims]{.underline}**

The Agency requires and reviews efficacy data for products making
labeling claims to control public health pests. A review of the
pesticide product labels containing Chitin and Chitosan reveals no
claims against public health pests. Accordingly, no efficacy data will
likely be required. Notwithstanding, a full review of label claims
remains incomplete pending the final registration review decision. As
appropriate, registrants will be required to resolve any outstanding
efficacy/labeling concerns in response to that final decision.

**[Timeline:]{.underline}**

EPA has created the following estimated timeline for the completion of
the Chitin and Chitosan Registration Review case. This schedule is
subject to revision should there be a need for a Data Call-in during the
registration review process or should other issues arise.

  ---------------------------------------------------- ------------------
  **Activities**                                       **Estimated
                                                       Month/Year**

  Open Public Comment Period for Chitin and Chitosan   September 2007
  Docket                                               

  Close Public Comment Period                          November 2007

  Develop Final Work Plan (FWP)                        January 2008

  Open Public Comment Period for Proposed Reg. Review  FY 2008 3^rd^
  Decision                                             Quarter

  Close Public Comment Period                          FY 2008 3^rd^
                                                       Quarter

  Final Decision                                       FY 2008 4^th^
                                                       Quarter

  Total (years)                                        1
  ---------------------------------------------------- ------------------

**[Guidance for Commenters:]{.underline}**

The public is invited to comment on EPA's preliminary registration
review work plan. Stakeholders are specifically asked to provide any
additional information regarding use information and any incident data
not already reported to the agency. In addition, the Agency welcomes any
comments regarding EPA's risk assessments and its anticipated decision
not to conduct further risk assessments. The Agency will carefully
consider all comments as well as any additional information or data
provided prior to issuing a final work plan for the Chitin and Chitosan
case.

Water quality concerns for Chitin and Chitosan are expected to be
non-existent since these pesticides are ubiquitous in nature and have a
very low toxicity profile. Public comment is invited on any water
quality concerns. Similarly, trade irritants aren't expected for this
pesticide since it is exempted from the requirements for a tolerance in
the U.S. Growers and other stakeholders are asked to comment on any
trade irritant issues for this pesticide.

**[Next Steps:]{.underline}**

After the comment period closes, the Agency will prepare a Final Work
Plan for this pesticide.

**II. CHITIN FACT SHEET**

[**Chitin Background Information**:]{.underline}

-   Registration review case number: 6063

-   Chemical Name: Poly-N-Acetyl-D-Glucosamine

-   PC Code: 128991

-   CAS#: 1398-61-4

-   Source material: Shells of crustaceans

-   Sole (and original) registrant: Igene Biotechnology

-   First approved for use in a registered product in 1988

-   Not subject to reregistration (no Reregistration Eligibility
    Decision \[RED\])

-   Exemption from The Requirement of a Tolerance: 40 CFR 180.1089; was
    reassessed September 12, 2003.

-   Registration Review Lead: Chris Pfeifer; <pfeifer.chris@epa.gov>

**[Description of the Active Ingredient:]{.underline}**

Chitin is a naturally occurring chain of glucose molecules that is
structurally related to cellulose. It is ubiquitous in nature. Chitin is
most commonly derived from crustacean shells, particularly from crabs
and shrimp. Historically, it has been used as a food additive and a
fertilizer. As a pesticide active ingredient, it acts by stimulating the
growth of certain microorganisms in soil, which release substances that
kill pathenogenic nematodes and their eggs. The compound is also reputed
to play a role as a plant growth regulator by bolstering plant defenses
against disease.

![](media/image1.png){width="3.0006944444444446in"
height="1.7173611111111111in"}

Chitin

**[Chitin Use Information:]{.underline}**

-   Chitin is used for controlling soil nematodes on crops (food and
    non-food), ornamentals and turf.

-   Use sites are residential and commercial. They include: agricultural
    fields, nurseries, greenhouses, sod farms, commercial turf grasses,
    golf courses, home lawns and gardens.

-   Application methods include: pre-plant soil incorporation and
    post-plant surface application followed by saturation.

-   Mode of action: Chitin acts in soil to stimulate the growth of
    naturally occurring microorganisms in the soil, which then release
    substances that kill pathogenic nematodes and their eggs.

-   Chitin is the active ingredient in CLANDOSAN 618, which is the sole
    registered pesticide product containing this active ingredient.

**[Recent Actions:]{.underline}**

There have been no recent significant regulatory activities regarding
the sole registered Chitin product (i.e. tolerance related actions,
changes of use patterns, submission of toxicology studies or incident
reports).

**[Ecological Risk Assessment Status]{.underline}**:

Ecological effects for Chitin were fully considered in the course of
reviewing the application for the first product containing this active
ingredient (CLANDOSAN 618). A registration decision document, issued in
March of 1988, concurred that Chitin posed negligible to non-existent
ecological risk. In that decision document, the Agency granted data
waivers for all nontarget data requirements relating to the application
of the Chitin-based pesticide, CLANDOSAN 618. It was determined that
under normal conditions, the proposed end uses would pose minimal
hazards to nontarget organisms. EPA noted the following as grounds for a
rationale: 1) historical data on Chitin demonstrating negligible
toxicity on humans and animals; 2) a ubiquity of Chitin in nature such
that applications of Chitin would likely fall within the existing range
of background concentrations; and 3) the ability of Chitin to degrade.
As a result of these considerations, the Agency does not anticipate the
need for new data or the need to conduct a new ecological risk
assessment for Chitin.

*Endangered Species Act:* An endangered species assessment for Chitin is
expected to be completed in October of 2007. The assessment document
will be added to the docket at that time. Potential commenters will also
have full opportunity to make comments during the 60 day comment period
when the assessment document is posted in the docket for the *Proposed
Registration Review Decision for Chitin* (FY 2008, 3^rd^ Quarter).

**[Human Health Risk Assessment Status:]{.underline}**

All biochemical pesticide toxicology data requirements applicable to a
human health effects determination for Chitin were considered and
fulfilled for the Chitin-based pesticide CLANDOSAN 618 in 1988. Acute
Oral Toxicity and Acute Eye Irritation studies specific to the pesticide
were both accepted as Toxicity Category IV. The balance of the Tier I
biochemical toxicology data requirements were satisfied through a public
literature submission, which further supported the case for Chitin's low
toxicity profile. Additional information used in making a human health
effects determination for Chitin included: 1) a bridging of data used to
establish an exemption from the requirement of a tolerance for Chitosan;
2) an approval by the FDA for the use of Chitin as a food additive; 3) a
history of unrestricted use of Chitin as a soil amendment, without a
record of incident; and 4) a recognition that any exposure gains
relative to pesticidal applications would be negligible, given Chitin's
ubiquity in nature. Altogether, the aforementioned information provided
sufficient grounds for section 3 registration and an exemption from the
requirement of a tolerance for Chitin -- 40 CFR 180.1089. As a result of
these considerations, the Agency does not anticipate the need for new
data or the need to conduct a human health risk assessment for Chitin.

**[Incidents:]{.underline}**

The OPP Incident Data System (IDS) indicates that there have been no
reports of human and domestic animal incidents for products containing
Chitin. The Agency will consider any additional incident~~s~~ data or
comments submitted in response to this docket.

**[Labels and Products]{.underline}:**

The sole registered product with Chitin as an active ingredient follows:

CLANDOSAN 618 (25% a.i.) EPA Reg. No. 54137-1 (formerly EPA Reg. No.
58200-9)

Labels for the above product~~s~~ can be obtained from the Pesticide
Product Label System (PPLS) website:
<http://oaspub.epa.gov/pestlabl/ppls.home>.

**III. CHITOSAN FACT SHEET**

[**Chitosan Background Information**:]{.underline}

-   Registration review case number: 6063

-   Chemical Name: Poly-D-Glucosomine

-   PC Code: 128930

-   CAS#: 9012-76-4

-   Source material: Chitin derived from the shells of crustaceans

-   End-use product registrants: Plant Defense Boosters, Inc; Chem-tex,
    Laboratories, Inc.

-   Chitosan was first approved for use as a Plant Growth Regulator
    (PGR) in a registered product in 1986.

-   Chitosan was registered for use as an antimicrobial agent in a
    registered product in 2003.

-   Not subject to reregistration (no Reregistration Eligibility
    Decision \[RED\])

-   Exemption from The Requirement of a Tolerance: 40 CFR 180.1072; was
    reassessed July 3, 2002.

-   Registration Review Lead: Chris Pfeifer; <pfeifer.chris@epa.gov>

**[Description of the Active Ingredients:]{.underline}**

Chitosan is a naturally occurring chain of glucose molecules that is
structurally related to cellulose. It is one of the most common
compounds in nature. Commercially, Chitosan is prepared through the
deacetylation of Chitin. Chitosan has several biomedical applications.
It is considered to be a hemostatic agent that is hypoallergenic and is
known to possess anti-bacterial properties. These properties also allow
for its use as an active ingredient in anti-microbial pesticides.
However, as a pesticidal active ingredient, Chitosan is best known as a
plant growth regulator that boosts the ability of plants to defend
against fungal infections.

![](media/image2.png){width="2.873611111111111in"
height="1.6256944444444446in"}

\* This diagram of the chemical structure of Chitosan is presented for
illustrative purposes, and is intended primarily as a generalized point
of comparison with Chitin. The actual chemical structure of Chitosan is
subject to substantial variations based on the degree of deacetylation
of Chitin.

**[Chitosan Use Information:]{.underline}**

-   As a pesticide, Chitosan is used as a Plant Growth Regulator (PGR),
    fungicide and an antimicrobial agent.

-   As a PGR, Chitosan's mode of action is characterized by its ability
    to bolster plant resistance against fungal diseases. Specifically,
    it purports protection against downy mildew, powdery mildew, early
    blight, late blight, gray mold, leaf spot, anthracnose and blast.

-   PGR use sites include: agricultural fields, nurseries, greenhouses,
    commercial turf grasses, and home gardens (food and ornamental).

-   As a PGR, it is produced in aqueous form and is applied by spray to
    plants throughout the growing season, with applications every one to
    two weeks as needed.

-   Chitosan is the active ingredient in ELEXA-4, which is the sole
    registered PGR product containing this active ingredient.

-   As an antimicrobial pesticide, Chitosan employs anti-bacterial
    properties to protect fabrics from bacterial and fungal growth.

-   The antimicrobial pesticide is produced as an aqueous solution and
    is either applied by spray or added to laundry's wash cycle.

-   Chitosan is the active ingredient in ChitoSante, which is the sole
    antimicrobial pesticide containing this active ingredient.

**[Recent Actions:]{.underline}**

There have been no recent significant regulatory activities regarding
either Chitosan product, (i.e. tolerance related actions, changes of use
patterns, submission of toxicology studies or incident reports).

**[Ecological Risk Assessment Status]{.underline}**:

As an active ingredient, Chitosan is employed in three distinct use
patterns -- as a PGR, as a fungicide on plants, and as an antimicrobial
agent. Ecological effects were considered with regard to each use
pattern.

With regard to Chitosan's initial use as a PGR, ecological effects were
first considered in 1986 when the applicant Natural AG submitted a mix
of general animal toxicity data and waiver requests to fulfill their
non-target data requirements in support of EPA Reg. No. 56437-1.
Subsequent registrations for Hyga, ELEXA, and ELEXA-4 were all granted
waivers for their non-target requirements based on like rationales. The
most recent review of non-target waiver requests occurred for ELEXA-4 in
March of 2000. The review took place in the Biopesticides and Pollution
Prevention Division (BPPD) and reflects the most current thinking on
ecological effects relative to Chitosan. In that review, it was
determined that under normal conditions, the proposed end uses would
pose minimal hazards to non-target organisms. BPPD noted the following
as grounds for its waivers: 1) copious amounts of historical data on
Chitosan demonstrating negligible toxicity on humans and animals; 2) a
ubiquity of Chitosan in nature such that proposed application rates
would likely fall within the existing range of background
concentrations; and 3) the ability of Chitosan to decompose. As a result
of these considerations, the Agency does not anticipate the need to
conduct an ecological risk assessment for the use of Chitosan as a PGR,
nor as a fungicide used on plants.

With regard to Chitosan's use as an antimicrobial agent, the Agency has
also found that ecological risk is unlikely. An August 2007 memo from
the Risk Assessment and Science Support Branch of the Antimicrobials
Division notes the following in support of this position: 1) Most uses
are indoors and allow for minimal environmental exposure. 2) Available
information and the prevalent use of Chitosan in food and drugs support
the case for Chitosan's relative nontoxicity. 3) Chitosan is a naturally
occurring compound that is common in nature. In sum, the Agency
anticipates that no ecological risk assessment will be necessary for
Chitosan when it is used as an antimicrobial active ingredient on
fabrics.

*Endangered Species Act:* An endangered species assessment for Chitosan
is expected to be completed in October of 2007. The assessment document
will be added to the docket at that time. Potential commenters will also
have full opportunity to make comments during the 60 day comment period
when the assessment document is posted in the docket for the *Proposed
Registration Review Decision for Chitin* (FY 2008, 3^rd^ Quarter).

**[Human Health Risk Assessment Status:]{.underline}**

Human health effects were considered with regard to each use pattern of
Chitosan. As a PGR and fungicide applied to plants, the Agency
anticipates that no additional human health effects data will be
required for Chitosan. Summary reviews indicate that data were
sufficient to fulfill all current biochemical pesticide toxicology data
requirements for Chitosan. Health effects data for Chitosan were first
found sufficient for the registration of EPA Reg. No. 56437-1 and the
issuance of an associated exemption from the requirement of tolerance in
1986. The exemption, found under 40 CFR 180.1072, was reaffirmed once
more in a 1995 review. The review based its approval on the following
information: 1) the original literature and data submitted in 1986
characterizing Chitosan's lack of toxicity; 2) approval by the FDA for
use of Chitosan as a food additive; 3) an extensive history of human use
and exposure, without record of incident; and 4) the relatively low
application rates. With regard to the recent standards of the Food
Quality Protection Act, a tolerance reassessment involved product
specific toxicological data and all applicable biochemical pesticide
toxicology data requirements. Studies were submitted and approved for
all Tier I biochemical toxicology data requirements. Waiver requests
were made and accepted for all other toxicological data requirements.
The Agency completed tolerance reassessment for Chitosan on July 3,
2002. Accordingly, the Agency does not anticipate that a human health
risk assessment will be needed for Chitosan when it is used as a PGR or
as a fungicide used on plants.

With regard to Chitosan's use as an antimicrobial agent, the Agency has
considered all applicable toxicology data requirements. A July 2003
summary memo notes the following toxicological profile for the sole
end-use product, Chitosante: Acute Dermal Toxicity, Acute Oral Toxicity,
Acute Inhalation Toxicity and Skin Irritiation are accepted as Toxicity
Category IV; Acute Eye is accepted as Toxicity Category III; and
Chitosante is deemed a Non-sensitizer. Based on the toxicity profile of
the end-use product and summary reviews characterizing the health
effects of Chitosan, the Agency anticipates that no human health risk
assessment will be necessary when Chitosan is used on fabrics as an
antimicrobial active ingredient.

**[Incidents:]{.underline}**

The National Pesticides Information Center (NPIC) database indicates
that there have been no reports of human and domestic animal incidents
for products containing Chitosan. The Agency will consider any
additional incidents data or comments submitted in response to this
docket.

**[Labels and Products]{.underline}:**

The following products have Chitosan as an active ingredient:

ELEXA-4 (4% a.i.) EPA Reg. No. 81045-2

ChitoSante (6% a.i.) EPA Reg. No. 81446-1

Labels for the above products can be obtained from the Pesticide Product
Label System (PPLS) website: <http://oaspub.epa.gov/pestlabl/ppls.home>.