Chitin and Chitosan Summary Document

Registration Review: Initial Docket

September 2007

TABLE OF CONTENTS

											Page #

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

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

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:

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 assessments, 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:

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:

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

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:

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 Docket 	September
2007

Close Public Comment Period 	November 2007

Develop Final Work Plan (FWP)	January 2008

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

Close Public Comment Period 	FY 2008 3rd Quarter

Final Decision 	FY 2008 4th Quarter

Total (years)	1



Guidance for Commenters:

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:

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

II. CHITIN FACT SHEET

 

Chitin Background Information:

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;   HYPERLINK
"mailto:pfeifer.chris@epa.gov"  pfeifer.chris@epa.gov 

Description of the Active Ingredient:

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. 

                                          Chitin

Chitin Use Information:  

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:

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: 

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, 3rd Quarter).

Human Health Risk Assessment Status:

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:

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 incidents data or
comments submitted in response to this docket.

Labels and Products: 

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 products can be obtained from the Pesticide Product
Label System (PPLS) website:   HYPERLINK
"http://oaspub.epa.gov/pestlabl/ppls.home" 
http://oaspub.epa.gov/pestlabl/ppls.home .  

III. CHITOSAN FACT SHEET

 

Chitosan Background Information:

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;   HYPERLINK
"mailto:pfeifer.chris@epa.gov"  pfeifer.chris@epa.gov 

Description of the Active Ingredients:

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.

 

* 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:  

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:

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: 

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, 3rd Quarter).

 

Human Health Risk Assessment Status:

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:

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: 

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:   HYPERLINK
"http://oaspub.epa.gov/pestlabl/ppls.home" 
http://oaspub.epa.gov/pestlabl/ppls.home . 

Docket Number: EPA-HQ-EPA-2006-0566

www.regulations.gov

 PAGE   

 PAGE   11 

Docket Number: EPA-HQ-EPA-2006-0566

www.regulations.gov

