Document ID: EPA-HQ-OPP-2012-0128-0009
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2012-10-18T04:00Z

BIOPESTICIDES REGISTRATION ACTION DOCUMENT
                                       
                                       
                                       
                                       
                                       
                                       
                                       

                                       
                                   Cellulose
                               PC Code: 100154
                                       
                                       
                                       
                                       
                                       
                                       
                                       
                                       
                                       

   
	U.S. Environmental Protection Agency
	Office of Pesticide Programs
                Biopesticides and Pollution Prevention Division
                                       
                                       
                               October 15, 2012
                                       
		TABLE OF CONTENTS				
I.	EXECUTIVE SUMMARY	5
II.	 ACTIVE INGREDIENT OVERVIEW	6
III.	 REGULATORY BACKGROUND	6
A.	Classification	6
B.	Food Clearances/Tolerances	7
IV.	  RISK ASSESSMENT	7
A.	Active Ingredient Characterization	7
B.	Human Health Assessment	7
1.	Toxicology	7
2.	Dose Response Assessment	10
    3.       Drinking Water Exposure and Risk Assessment.................................................................10
4.	Occupational, Residential, School and Day Care Exposure and Risk Characterization	11
5.	Risk Characterization	11
C.	Environmental Assessment	12
1.	Ecological Hazards	11
2.	Environmental Fate and Ground Water 	12
3.	Ecological Exposure and Risk Characterization	12
4.	Endangered Species Assesment	12
D.	 Efficacy Data	12
V.	Risk Management Decision	13
A.	Determination of Eligibility for Registration	13
B.	Regulatory Decision	13
VI.	 ACTIONS REQUIRED BY REGISTRANTS	14
A.  Reporting of Adverse Effects	14
B.	Reporting of Hypersensitivity Incidents	14
VII.	 Appendix A. Data Requirements (40 CFR Part 158)	14
VIII. Appendix B. Product Specific Information.	18
IX.	Appendix C. References.	18

BIOPESTICIDES REGISTRATION ACTION DOCUMENT (BRAD) TEAM

Branch Chief
Linda A. Hollis, M.S.

Product Chemistry/Human Health Effects/Nontarget Organisms
Angela L. Gonzales, Biologist

Efficacy
Clara Fuentes, Ph.D., Entomologist

Senior Regulatory Specialist
Leonard S. Cole, Jr., M.S.
I.	EXECUTIVE SUMMARY
Cellulose is a new biochemical pesticide active ingredient intended for use as a rodenticide for the control of mice in commercial and residential indoor settings. Cellulose is derived from corn cobs that have been dried and ground into coarse granules. Cellulose is a polysaccharide and the main constituent of plant cell walls. It is also produced by some algae, fungi and bacteria. Cellulose is used in a variety of products including paper, textiles and building materials (French, 2003). Various derivatives of cellulose including powdered cellulose and microcrystalline cellulose are approved by the U.S. Food and Drug Administration (FDA) for use in food and pharmaceutical products under 21 CFR § 175.105 as a thickening agent.   
The Biopesticides and Pollution Prevention Division (BPPD) determined that the data/information submitted to address product chemistry and Tier I acute toxicity data requirements satisfy the current guideline requirements. Acceptable data and information were submitted for the subchronic 90-day oral (OCSPP 870.3100), 90-day dermal (OCSPP 870.3250), 90-day inhalation (OCSPP 870.3465), mutagenicity in vitro mammalian cell assay (OCSPP 870.5100), mutagenicity in vivo micronucleus assay (OCSPP 870.5395) and developmental toxicity (OCSPP 870.3700) data requirements. BPPD has evaluated the relevant data and information and concluded that, based on the use pattern for cellulose as proposed to be registered and reflected in the proposed registration label, significant exposure to humans is not anticipated from the use of cellulose. 
At the request of the applicant, non-target organism data requirements for this product were waived on the basis that the guideline studies were not applicable because the proposed registration will only permit indoor use. Thus, non-target toxicity is not anticipated because of lack of exposure. Based on its non-target assessment, EPA has determined that the proposed registered use of cellulose in end use products (EPs) should not result in adverse effects to birds, fish, aquatic invertebrates, plants, or non-target insects.

Based on the acute toxicity data for cellulose, the active ingredient is toxicity category III for primary dermal irritation. EPA has not identified any toxic endpoints for non-target mammals, birds, plants, aquatic, or soil organisms. EPA has no concerns for any non-target organisms exposed to cellulose when used in accordance with approved label directions. Given that cellulose has very low toxicity and presents little, if any, risk to non-target organisms, EPA has concluded that it is in the best interests of the public to issue the registration for the cellulose MP (EPA File Symbol 84889-R) and the EP (EPA File Symbol 84889-E).  

BPPD has reviewed the data/information in support of the requirements for granting registration under Section 3(c)(5) of the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA). It has been determined that the data/information submitted adequately satisfy current guideline requirements (please refer to 40 CFR Subpart U § 158.2000). 

On October 1, 2009, EPA announced a new policy to provide a more meaningful opportunity for the public to participate on major registration decisions before they occur. According to this policy, EPA provides a public comment period prior to making a registration decision for the following types of applications: new active ingredients, first food use, first outdoor use, first residential use; and any registration decisions for which the Agency believes there may be substantial public interest.  

Consistent with the policy of making registration actions more transparent, cellulose is subject to a 15 day comment period as a "new active ingredient". The notice for this comment period includes a draft Biopesticides Registration Action Document (BRAD) and draft product labels for PCC 38-DD, the (MP) and Rode-Trol, the (EP) which contain the new active ingredient, cellulose. The docket identification (ID) number is EPA-HQ-OPP-2012-0128. The Agency believes that based on the risk assessment and information submitted in support of the registration of the MP and the EP, it is in the best interests of the public to issue the registration for Rode-Trol as a rodenticide. The basis for this decision can be found in the risk assessment for cellulose, which is characterized in this BRAD.  
                                        
II.		ACTIVE INGREDIENT OVERVIEW

   Common Name: 			Cellulose
   
      Chemical Names:            N/A
 
   Trade & Other Names: 	Powdered Corn Cobs

      CAS Registry Number: 	9004-34-6
   
   OPP Chemical Code: 	100154

   Type of Pesticide:            Biochemical Pesticide (Rodenticide) 

III.		REGULATORY BACKGROUND

On July 12, 2011, EPA received an application filed by Exponent, 1150 Connecticut Avenue, NW, Suite 1100, Washington, DC 20036, on behalf of Rode-Trol, LLC, 35801 Road 132, Visalia, CA 93292, to register the products, PCC 38-DD (EPA File Symbol No. 84889-R) and Rode-Trol (EPA File Symbol No. 84889-E) containing the new biochemical active ingredient, cellulose. A notice of receipt (NOR) of this application, allowing for a 30-day comment period, was published in the Federal Register on February 29, 2012 (77 FR 12296). No comments were received following this publication.

A.	Classification

On June 22, 2006, the biochemical classification committee determined that cellulose is a biochemical.

 

B.	Food Clearances/Tolerances 

This active ingredient is not registered for use on food or feed commodities. A tolerance or exemption from the requirement of a tolerance is not required for the current uses.

IV.			RISK ASSESSMENT
 
A.	Active Ingredient Characterization
Powdered corn cobs are shelled corn cobs that have been dried and ground. Cellulose which is the actual pesticidal component in the cobs, comprises approximately 37% of the powdered corn cobs. The mode of action of cellulose as a rodenticide is believed to be interference with osmoregulation in the intestines of rats and mice which results in dehydration, malnutrition and consequently death. A second theory regarding the mode of action of the active ingredient is that because cellulose is indigestible by non-ruminant mammals, consumption of excessive amounts of the material may result in intestinal dysfunction. 
Cellulose, a polysaccharide, is one of the most abundant organic compounds on Earth. It is the main constituent of plant cell walls and is also produced by some algae, fungi and bacteria. It is consumed in its natural state (as a component of plants) by humans and animals and is used in a variety of products, such as paper, textiles and building materials. (French, 2003) Various derivatives of cellulose, including powdered cellulose and microcrystalline cellulose are approved by the FDA for use in food and pharmaceutical products as a thickening agent (21 CFR). Under the Federal Food, Drug and Cosmetic Act (FFDCA), EPA has exempted the compound from the requirement of a tolerance as a minimum risk active and/or inert ingredient in food-use pesticide products (40 CFR 180.950(e)). The Agency has also approved cellulose as a nonfood-use inert ingredient in pesticide products. In 2007, cellulose from powdered corn cobs was approved for use as a rodenticide in Canada by the Pest Management Regulatory Agency (PMRA).   

All product chemistry data requirements for the registration of cellulose have been satisfied. 

For more information regarding product chemistry data requirements, refer to Tables 1 and 2 in Appendix A.  
	
B.	Human Health Assessment

1.	Toxicology 

To satisfy the toxicology data requirements, data were provided from the open scientific literature. Reviews and analyses of these data by the World Health Organization (WHO) and PMRA were also submitted. For all data requirements adequate data on surrogate chemicals such as microcrystalline cellulose or refined-alpha cellulose were submitted. These chemicals are derivatives of cellulose. In lieu of submitting data on the toxicity for powdered corn cobs, data were submitted on cellulose because the compound is considered to be the pesticidal component of the powdered corn cobs. The data submitted are acceptable to qualitatively assess the toxicity of the active ingredient. 

All toxicology data requirements have been satisfied in accordance with 40 CFR § 158.2050.  The data presented in Table 3 below are a summary of the toxicity data for powdered corn cobs (cellulose). Data evaluation records (DERs) were not created for the submitted MRIDs; however, the data and information from these MRIDs are summarized in Table 3 and in the subsequent sections.

Adequate mammalian toxicology data/information is available to support registration of cellulose. All toxicology data requirements for cellulose have been satisfied.

	a.	Acute Toxicity

All data submitted to support the acute toxicology data requirements were collected from the open scientific literature and were obtained from studies conducted on acceptable surrogate chemicals for cellulose, such as microcrystalline cellulose. Microcrystalline cellulose is purified, partially depolymerized cellulose (MRID 48433405, p. 95 of 110). Based on the available data and information, the Agency has classified cellulose as having low acute oral, acute dermal and acute inhalation toxicity. It is minimally irritating to the eye, is not a dermal irritant and is not a dermal sensitizer.  

All of the acute toxicity data referenced above were also reviewed by the World Health Organization (WHO) and Canada's Pest Management Regulatory Agency (PMRA) and found to be acceptable.

 	b.	Subchronic Toxicity 
 
90-Day Oral

The 90-day oral data requirement is conditionally required for nonfood uses that are likely to result in repeat oral exposure to humans.  The proposed product is intended for use to formulate EPs which will be used as rodenticides in indoor settings. Repeat human oral exposure is not expected based on the proposed use pattern of the product. The proposed product will be placed in bait stations and/or trays and left alone to attract rodents.  Label instructions will include precautionary statements to mitigate exposure to applicators and children. Any oral exposure is likely to be accidental; repeated oral exposure is not anticipated. In the case that accidental exposure should occur, hazard data indicate that ingestion of cellulose is not likely to result in toxic effects. Several subchronic and chronic oral toxicity studies were cited (actual studies were not provided) in MRID 48534106 for derivatives of cellulose. Most of the studies were conducted using microcrystalline cellulose. In their safety evaluation of microcrystalline cellulose, the WHO reviewed these studies and concluded that there is no evidence to indicate that consumption of microcrystalline cellulose in foods (when foods are produced according to good manufacturing processes) will result in toxic effects in humans (MRID 48433405, p. 25 of 100). Moreover, humans are already naturally exposed via the oral route to cellulose through consumption of plants and other foods.

90-Day Dermal

The 90-day dermal data requirement is conditionally required to support uses involving purposeful application to the human skin or uses that would result in prolonged dermal exposure and if data from a 90-day oral study are not required or the active ingredient is known or expected to be metabolized differently by the dermal route of exposure than by the oral route and the metabolite is of toxicological concern. Purposeful application and prolonged exposure to the human skin is not anticipated based on the use pattern of the proposed product (the product will be placed in bait stations and/or trays and left alone to attract rodents). Label instructions will include precautionary statements to mitigate exposure to children. Additionally, humans are already exposed via the dermal route to cellulose in paper products, textiles, foods and plants.

90-Day Inhalation

The 90-day inhalation data requirement is conditionally required if there is a likelihood of significant levels of repeated inhalation exposure to the pesticide as a gas, vapor or aerosol. Cellulose is lowly toxic via the inhalation route of exposure.  For the proposed uses of powdered corn cobs (cellulose) as a pesticide, repeated inhalation exposure is unlikely based on the physical properties of the active ingredient, which is a solid. The proposed EP is formulated as a pellet that is not inhalable. Although dust may be generated from the product containing the active ingredient during shipping and/or handling, significant exposure is not anticipated. Should exposure occur however, it is expected to be brief in duration.  Moreover, the use pattern of the product significantly limits exposure since the active ingredient is housed in bait stations and/or trays.  

	c.   Developmental Toxicity 

Developmental toxicity data are conditionally required if significant exposure to female humans is expected from the proposed product's use under widespread and commonly recognized practice. Significant exposure to females is unlikely based on the proposed use pattern of the product containing the active ingredient (the product will be placed in bait stations and/or trays and left alone to attract rodents). If used according to label instructions, significant oral, dermal and inhalation exposure to the active ingredient is not anticipated. No developmental toxicity effects were observed in studies with microcrystalline cellulose reviewed by the WHO (MRID 484334-05, p. 21 of 110). 

	d.   Mutagenicity

Mutagenicity data are conditionally required to support nonfood uses if the use is likely to result in significant human exposure or if the active ingredient or its metabolites are structurally related to a known mutagen or belong to any chemical class of compounds containing a known mutagen.  Significant human exposure is unlikely based on the use pattern (the proposed EP will be placed in bait stations or in trays and left alone to attract rodents). Additionally, the proposed EP is for nonfood-uses only. Moreover, in studies reviewed by the WHO, microcrystalline cellulose was not mutagenic in various in vitro mutagenicity assays in Salmonella typhimurium and Escherichia coli and it was not mutagenic in in vivo mouse erythrocyte micronucleus mutagenicity assays. 

	e.   Companion Animal/Nontarget Animal Toxicity and Risk Characterization
To assess the potential for hazardous effects to various species, including pets, which may encounter the product containing the active ingredient during use, several non-guideline toxicity studies were conducted and submitted to the Agency (MRIDs 48433507-48433516). The species tested were: brushtail possum (Trichosurus vulpecula), rabbit (Oryctolagus cuniculus cuniculus), guinea pig (Cavia porcellus), cat (Felis catus), dog (Canis familiaris), ferret (Mustela furo), chicken (Gallus gallus), duck (Anas platyrhynchos) and goldfish (Carassius auratus). In each study, test species were deprived of their normal diet for 24 hours and then presented with the product containing the active ingredient and a half-ration of their normal food. The feeding schedule continued for up to 10 days. Animals were observed for daily consumption and changes in body weight and behavior. Animals that consumed at least 5g test substance/kg body weight were euthanized and examined for gross pathological effects. Possums, cats, chickens, dogs and ferrets typically refused the product after sampling small to moderate quantities. Guinea pigs, rabbits and male ducks consumed appreciable amounts of the product over the testing period. No changes in behavior were observed in any of these species during the test period. Gross pathology observations were normal for these species with the exception of observations of possible reduced urine production in possums, guinea pigs and rabbits and dry feces in some ducks. Goldfish mortality occurred between the first day and 19 days post-application (the product was applied to simulate an accidental spillage into a fish tank or pond). It was not determined if mortality occurred due to water contamination from the product or from consumption of the product. 
Based on the data provided, the product appears to be unpalatable to possums, cats, chickens, dogs and ferrets. Should accidental consumption occur, the available data indicate that accidental exposure should not result in toxic effects to these species. Although guinea pigs, rabbits and ducks may consume the product, the available data indicate that accidental exposure should not result in toxic effects. Accidental exposure to fish may result in mortality based on the data submitted; however, exposure is not expected based on the use pattern of the product. Risk to all of the above species is expected to be negligible based on minimal toxicity and lack of exposure if label instructions are followed.   
   
2.	Dose Response Assessment

Because no toxicological endpoints were identified for this active ingredient, a dose response assessment was not required.  

3.	Drinking Water Exposure and Risk Characterization

Based on the proposed use pattern of powdered corn cobs (cellulose) as a rodenticide, pesticide residues in drinking water are not expected when products are used according to label instructions. Products containing the active ingredient will be used in indoor commercial and residential settings only; therefore, cellulose residues in drinking water are unlikely.   

4.	Occupational, Residential, School and Day Care Exposure and Risk Characterization

	a.  Occupational Exposure and Risk Characterization

An occupational exposure assessment was not conducted for powdered corn cobs (cellulose) because significant exposure to workers, handlers and applicators is not anticipated given that the active ingredient is housed in bait stations or trays (which limits exposure) and is not likely to be directly handled when used in accordance with label directions. Cellulose is of low toxicity and should exposure occur, it is likely to be via the dermal and possibly the inhalation route and expected to be brief in duration. Once the bait stations or trays are placed in the areas, they are left alone to attract rodents. There is a likelihood of exposure from inhalation to dust generated during the life-cycle of the product. This exposure is not expected to be significant and again, brief in duration.  Moreover, should dermal or inhalation exposure occur significant risks are not anticipated because the active ingredient is of low dermal and inhalation toxicity and therefore, the Agency believes that use of this product presents no unreasonable risks. Humans are already exposed to cellulose in the diet and through use of various products such as paper and textiles, with no reports of adverse effects. There were no relevant toxicological endpoints were identified in the data submitted.  

   b.  Residential, School and Day Care Exposure and Risk Characterization

A residential, school and day care exposure assessment was not conducted for powdered corn cobs (cellulose).  Based on the proposed use pattern and toxicity data available to the Agency, anticipated exposure is not likely to result in unreasonable risk to humans.  No relevant toxicological endpoints were identified and significant exposure is not expected if label instructions are followed. Any exposure in residential, school and/or day care settings is likely to be accidental and data available to the Agency indicate that the active ingredient is of low toxicity. Additionally, humans are already exposed to cellulose in the diet and through use of various products such as paper and textiles.   

5.	Risk Characterization

Risk to humans from pesticidal use of powdered corn cobs (cellulose) is expected to be negligible due to the low toxicity of the active ingredient and the anticipated lack of exposure to humans as a result of its use pattern. The proposed product is not used in or on food, and is not directly applied to humans. Appropriate precautionary language requirements on end-use product labels will further mitigate exposure. 

The Agency has considered powdered corn cobs (cellulose) in light of the relevant safety factors in FIFRA.  A determination has been made that no unreasonable adverse effects to the U. S. population in general, and to infants and children in particular, will result from the use of this chemical when label instructions are followed.

C.	Environmental Assessment

1.  Ecological Hazards 

All non-target toxicology data requirements have been satisfied in accordance with 40 CFR 158.2060.  The information presented in Table 4 below is a summary of the non-target toxicology data and information for powdered corn cobs (cellulose). DERs were not created for the submitted MRIDs; however, data and information from these MRIDs are summarized in Table 4 and in the subsequent sections.   

2.	Environmental Fate and Ground Water Data 

Environmental fate and groundwater data are not required at this time because the results of the nontarget organism toxicity assessment (Tier I data requirements) did not trigger these Tier II data requirements.  

3.	Ecological Exposure and Risk Characterization

A risk assessment was not conducted for nontarget organisms due to the unlikelihood of exposure to nontarget organisms through the use of this product. Unreasonable effects to nontarget organisms are not anticipated; however, products should be used according to label instructions.  

4.	Endangered Species Assessment

The Agency has not conducted a risk assessment that supports a complete endangered species determination.  The ecological risk assessment planned during registration review will allow the Agency to determine whether powdered corn cobs' (cellulose) use has "no effect" or "may effect" federally listed threatened or endangered species (listed species) or their designated critical habitats.  When an assessment concludes that a pesticide's use "may affect" a listed species or its designated critical habitat, the Agency will consult with the U.S. Fish and Wildlife Service and/or National Marine Fisheries Services (the Services) as appropriate.  

D.	 Efficacy Data 

Data and information in MRIDs 48433517 to 48433524 demonstrate that the proposed product kills rats and mice when they are fed exclusively on the product for a period of approximately 7 days for rats and 3 days for mice.  The submitted efficacy data include a summary of laboratory studies conducted on the same formulation under different trade names and support the conclusion that the product causes mortality in rats and mice.  The product causes physical disruption of the feeding mechanism in rats and mice.  Mortality is caused by dehydration and malnutrition.  Several postulated pathological pathways were investigated and none were established as the physiological mechanism leading to these lethal outcomes.  It is unknown how normal food consumption in addition to Rode-Trol would have influenced product performance since the mortality effects of Rode-Trol were tested by feeding the rodents exclusively on the product. Given this uncertainty, not with respect to whether or not the product causes mortality, but how soon it would take the rats/mice to die as a result of feeding on the product in addition to alternative food sources, the product label must accurately reflect the conditions of testing. Product performance data directly impact the label, its claims and directions for use.  For the Rodetrol end use product, which is a product for indoor use only, the directions use for use must state "when applying the bait stations or trays, remove all alternative food sources from the treated area."

V.	RISK MANAGEMENT DECISION

A.	Determination of Eligibility for Registration 

Section 3(c)(5) of FIFRA provides for the registration of a new active ingredient if it is determined that: (A) its composition warrants proposed claims; (B) its labeling and other materials comply with the requirements of FIFRA; (C) it will perform its intended function without unreasonable adverse effects on the environment; and (D) when used in accordance with widespread and commonly recognized practice, it will not generally cause unreasonable adverse effects on the environment. 

The four criteria of the Eligibility Determination for Pesticidal Active Ingredients are satisfied by the science assessments supporting the end use product containing the manufacturing use product, cellulose. The end use product is not expected to cause unreasonable adverse effects. Therefore, cellulose as a manufacturing use product is eligible for registration for the labeled uses.  
   
B.	Regulatory Decision

The data submitted fulfill the registration requirements of cellulose for use as a rodenticide. Refer to Appendix B for product-specific information.

      	Conditional/Unconditional Registration

All data requirements are fulfilled, and EPA has determined that an unconditional registration of cellulose is appropriate.

C. Environmental Justice

EPA seeks to achieve environmental justice -- the fair treatment and meaningful involvement of all people regardless of race, color, national origin, or income -- with respect to the development, implementation, and enforcement of environmental laws, regulations, and policies. At this time, EPA does not believe that use of tagetes oil pesticide products will cause harm or a disproportionate impact on at-risk communities. For additional information regarding environmental justice issues, please visit EPA's website at http://www.epa.gov/compliance/environmentaljustice/index.html.

VI.	  ACTIONS REQUIRED BY REGISTRANTS

EPA evaluated all data submitted in connection with the registration of the cellulose pesticide product and determined that these data are sufficient to satisfy current registration data requirements. 

Notwithstanding the information stated in the previous paragraph, it should be clearly understood that certain specific data are required to be reported to EPA as a requirement for maintaining the Federal registration for a pesticide product. A brief summary of these types of data are listed below. 

A.  Reporting of Adverse Effects
   
Pursuant to FIFRA section 6(a)(2), reports of all incidents of adverse effects to the environment must be submitted to EPA.
B.REPORTING OF HYPERSENSITIVITY INCIDENTS
   
Additionally, all incidents of hypersensitivity (including both suspected and confirmed incidents) must be reported to the Agency under the provisions of 40 CFR Part 158.2050(d).

VII.   APPENDIX A. Data Requirements (40 CFR Part 158-Subpart U)

*NOTE:  Master Record Identification (MRID) numbers listed in the following tables are representative of supporting data/information for the original registration of the product containing this active ingredient. Subsequent to this registration, there may be additional MRIDs that support registration of other products containing this active ingredient.   

TABLE 1. Product Chemistry Data Requirements for Powdered Corn Cobs (Cellulose) (40 CFR § 158.2030)
                             OSCPP Guideline No. 
                                     Study
                                   Results 
                                     MRID
                                   830.1550
                                      to
                                   830.1670
Product identity;
Manufacturing process;
Discussion of formation of unintentional ingredients
Submitted data satisfy the requirements for product identity, manufacturing process, and discussion of formation of impurities
48433401
48534109
                                   830.1700
Analysis of samples
Submitted data satisfy the requirements for analysis of samples. 
48924801
                                   830.1750
Certification of limits
Limits listed in the CSF are acceptable.
48433401
48534109
                                   830.1800
Analytical method
Acceptable.
48433401

                                       
TABLE 2. Physical and Chemical Properties of Powdered Corn Cobs (Cellulose) (40 CFR § 158.2030)
                               OCSPP Guideline 
                                   Property
                             Description of Result
                                   (PC 38-DD)
                                     MRID
830.6302
Color
Yellow-brown
                                   48433402
830.6303
Physical State
Solid
                                   48433402
830.6304
Odor
Faintly sweet
                                   48433402
830.6313
Stability to Normal and Elevated Temperatures, Metals and Metal Ions
Stable
                                   48433402
830.6315
Flammability
Flash point: 388ºF (open cup); 396 ºF (closed cup)
                                   48433402
830.6317
Storage Stability
Rationale is inadequate
                                   48433402
830.6319
Miscibility
N/A: product is not an emulsifiable liquid that will be diluted with petroleum solvents
                                   48433402
830.6320
Corrosion Characteristics
Rationale is inadequate
                                   48433402
830.7000
pH
N/A: TGAI/MP is not soluble or dispersible in water
                                   48433402
830.7050
UV/Visible Light
Absorption
Data are not necessary to inform the risk assessment
                                   48433402
830.7100
Viscosity
N/A: product is a solid
                                   48433402
830.7200
Melting Point/Range
Not expected to melt
                                   48433402
830.7220
Boiling Point/Range
N/A: TGAI is a solid
                                   48433402
830.7300
Bulk Density
 28.0 lb/ft[3]
                                   48433402
830.7520
Particle Size, Fiber Length and Diameter Distribution
Coarse dust index: 0.89
Coarse dust: 9.78 X 10[-5] %
Crude fiber: 36.9%
                                   48433402
830.7550
830.7560
830.7570
Partition Coefficient (n-
Octanol/Water)
Data are not necessary to inform the risk assessment
                                   48433402
830.7840
Water Solubility
6.3% in water
                                   48433402
830.7950
Vapor Pressure
N/A: TGAI/MP is a solid
                                   48433402

Table 3. Mammalian Toxicology Data for Powdered Corn Cobs (Cellulose)  (40 CFR § 158.2050)
                           Study/OCSPP Guideline No.
                                    Results
                         Toxicity Category/Description
                                     MRID
Acute oral toxicity (rat)
(870.1100)
                      LD50 > 3160 mg/kg[1][,3] (males)
                LD50 > 5000 mg/kg[2][,3] (females and males)
                                      IV
                                   48433405
                                   48534101
Acute dermal toxicity (rat)	
(870.1200)
                LD50 > 2000 mg/kg[2][,3] (females and males)
                                      III
                                   48433405
                                   48534102
Acute inhalation toxicity	 (rat)
(870.1300)
                  LC50 > 5.35 mg/L2,3 (females and males)
                                      IV
                                   48433405
                                   48534103
Primary eye irritation (rabbit)	
(870.2400)
                            Minimally irritating[2]
                                      IV
                                   48433405
                                   48534104
Primary dermal irritation (rabbit)
(870.2500)
                               Nonirritating[2]
                                      IV
                                   48433405
                                       
Dermal sensitization (guinea pig)
(870.2600)
                              Not a sensitizer[2]
                                      N/A
                                   48433405
                                   48534105
90-Day oral toxicity 
(870.3100)
The proposed EP is nonfood-use. Uses are not anticipated to result in repeat oral exposure to humans.

Based on the review of available toxicity studies, the World Health Organization (WHO) has concluded that there is no evidence to indicate that consumption of microcrystalline cellulose in foods (when foods are produced according to good manufacturing processes) will result in toxic effects in humans. Humans are already naturally exposed to cellulose through consumption of plants and other foods.
                                       
                                       
                                       
                                       
                                       
                                       
                                   48433405
                                   48534106
                                       
                                       
90-Day dermal toxicity 
(870.3250)
Purposeful application and prolonged exposure to the human skin is not anticipated based on the use pattern (the proposed EP will be placed in bait stations or in trays and left alone to attract rodents). Additionally, humans are already exposed to cellulose and cellulose derivatives in paper products, textiles, pharmaceuticals, foods and plants.
                                       
                                       
90-Day inhalation toxicity
(870.3465)
Significant repeat inhalation exposure to the active ingredient as a gas, vapor or aerosol is unlikely based on the physical properties of the active ingredient. Powdered corn cobs (cellulose) are a solid material and the proposed EP is formulated as a pellet which is not inhalable. Although dust may be generated during the life-cycle of the product, significant exposure is not anticipated and the active ingredient is of low inhalation toxicity. The use pattern also precludes exposure (the proposed EP will be placed in bait stations or in trays and left alone to attract rodents). 
                                       
                                       
Mutagenicity-in vitro studies
(870.5100)
Significant human exposure is unlikely based on use pattern (the proposed EP will be placed in bait stations or in trays and left alone to attract rodents). The proposed EP is for nonfood-uses only. 

Various mutagenicity assays with microcrystalline cellulose in Salmonella typhimurium and Escherichia coli were reviewed by the WHO. All results were negative for genotoxicity.
                                       
                                       
                                       
                                       
                                       
                                       
                                   48433405
                                   48534108
                                       
Mutagenicity-in vivo micronucleus assay (870.5395)
Significant human exposure is unlikely based on use pattern (the proposed EP will be placed in bait stations or in trays and left alone to attract rodents). The proposed EP is for nonfood-uses only. 

In vivo mouse erythrocyte micronucleus mutagenicity assays using microcrystalline cellulose were reviewed by the WHO. All results were negative for genotoxicity.
                                       
                                       
                                       
                                       
                                       
                                       
                                   48433405
                                   48534108
                                       
Developmental toxicity
 (870.3700)
Significant female human exposure is unlikely based on use pattern (the proposed EP will be placed in bait stations or in trays and left alone to attract rodents). The proposed EP is for nonfood-uses only. 

No developmental toxicity effects were observed in studies with microcrystalline cellulose reviewed by the WHO. 
                                       
                                       
                                       
                                       
                                       
                                   48433405
                                   48534107
                                       
[1]Test substance was refined alpha-cellulose.
[2]Test substance was 85% microcrystalline cellulose.
[3]Highest dose tested.

VIII.   APPENDIX B.

For product specific information, please refer to http://www.epa.gov/pesticides/pestlabels.

IX.	  APPENDIX C. References
 
French, A. D., Bertoniere, N. R., Brown, R. M., Chanzy, H., Gray, D., Hattori, K. and Glasser, W. 2003. 
	Cellulose. Kirk-Othmer Encyclopedia of Chemical Technology. Published Online: October 17, 2003
 
 REVIEWS AND OTHER REFERENCES
 
 U.S. EPA. 2012. Memorandum from Clara Fuentes, Ph.D. to Leonard S. Cole, Jr. Science review of Rodetrol performance against rats and mice.  The active ingredient in the product is powdered corn cobs, containing 45.1% w/w cellulose. April 25, 2012.

U.S. EPA. 2012. Memorandum from Angela L. Gonzales to Leonard S. Cole, Jr. Science Review in Support of PCC 38-DD, Containing 100% Powdered Corn Cobs (37% Cellulose) As Its Active Ingredient.  October 3, 2012.
  
U.S. EPA. 2010. Memorandum from Angela L. Gonzales to Leonard S. Cole, Jr. Science Review in Support of Rode-Trol, Containing 90.0% Powdered Corn Cobs (33.3% Cellulose) As Its Active Ingredient. October 3, 2012.  
 
 X.    GLOSSARY OF ACRONYMS AND ABBREVIATIONS
      
   a.i.	active ingredient
   BPPD	Biopesticides and Pollution Prevention Division
   BRAD	Biopesticide Registration Action Document
   bw	body weight
   CBI	Confidential Business Information
   CFR	Code of Federal Regulations
   
   cm[3] 	cubic centimeter
   CSF	Confidential Statement of Formula
   °C 	degrees Celsius
   EC50	median effective concentration. A statistically derived single concentration in environmental medium that can be expected to cause an effect in 50% of the test animals when administrated by the route indicated (inhalation). It is expressed as a concentration in air or water (e.g. mg/L).
   EDSP	Endocrine Disruptor Screening Program
   EDSTAC	Endocrine Disruptor Screening and Testing Advisory Committee
   EP	end-use product
   EPA	Environmental Protection Agency (the "Agency")
   FDA	Food and Drug Administration
   FFDCA	Federal Food, Drug, and Cosmetic Act
   FIFRA	Federal Insecticide, Fungicide, and Rodenticide Act
   FQPA 	Food Quality Protection Act
   FR	Federal Register
   g 	gram
   ha	hectare
   kg	kilogram
   Kow	octanol-water partition coefficient
   L                   liter
   LC50	median lethal concentration. A statistically derived single concentration in air or water that can be expected to cause death in 50% of the test animals when administrated by the route indicated (inhalation and environment). It is expressed as a concentration in air or water (e.g. mg/L).
   LD50	median lethal dose. A statistically derived single dose that can be expected 
   	to cause death in 50% of the test animals when administered by the route 
   	indicated (oral and dermal). It is expressed as a weight of 
   	substance per unit weight of animal (e.g., mg/kg).
   MRID No.	Master Record Identification Number
   mg	milligram
   mPa	millipascal
   mL	milliliter
   MP	manufacturing-use product
   N/A	not applicable
   NE	"No Effect"
   NIOSH 	National Institute for Occupational Safety and Health
   nm	nanometer
   NOEL	no-observed-effect-level
   NOF	notice of filing
   NOR	notice of receipt
   OPP	Office of Pesticide Programs
   OCSPP 	Office of Chemical Safety and Pollution Prevention
   pa	pascal
   PPE 	personal protective equipment
   PR Notice	Pesticide Registration Notice
       TGAI 	   technical grade of the active ingredient
       ug 		   microgram
       USDA 	   United States Department of Agriculture
       UV 	   ultra-violet