**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**Cellulose**

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2 **TABLE OF CONTENTS I.**  **EXECUTIVE SUMMARY ................................**  **................................ ................................**  **.. 5**  **II. ACTIVE INGREDIENT OV** **ERVIEW ................................**  **................................ ..............**  **6 II**  **I. 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 Exposur**  **e and Risk Assessment.................................................................10 4.**  **Occupational, Residential, School and Day Care Exposure and Risk Characterization ......................**  **11 5.**  **Risk Characterization ................................**  **................................ ................................**  **................................ .**  **11 C.**  **E nvironmental 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 DECI SION**  **................................ ................................**  **................. 13**  **A. Determination of Eligibility for Registration**  **................................ ................................**  **.. 13**  **B. Regulatory Decision**  **................................ ................................**  **................................ ...........**  **13 VI.**  **ACTIONS REQUIRED BY REGISTRANTS**  **................................ ................................**  **. 14**  **A. R** **eporting of Adverse Effects ................................**  **................................ ............................**  **14 B.**  **Reporting of Hypersensitivity Incidents ................................**  **................................ ..........**  **14 VII.**  **APPENDIX A. Data Requirements**  **(40 CFR Part**  **158) ................................**  **................. 14**  **VIII. APPENDIX B. P roduct**  **S pecific**  **I nformation**  **. ................................**  **................................ 18** **Cellulose**

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3 **IX. APPENDIX C**  **. R eferences**  **. ................................**  **................................ ................................**  **18 Cellulose** 

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4 

### BIOPESTICIDES REGISTRATION ACTION DOCUMENT **(BRAD) TEAM**  

## Branch Chief Linda A. Hollis, M.S. **Product Chemistry/ Human**  **Health Effects/Nontarget Organisms** Angela L. Gonzales, Biologist **E fficacy**  Clara Fuentes, Ph.D., Ent o mologist **Senior Regulatory**  **Specialist** Leonard S. Cole, Jr., M.S.**Cellulose**

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5 **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 poly saccharide 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 microcry stalline 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 i n the proposed registration label , s ignificant exposure to humans is not anticipated from the use of cellulos e. At the request of the applicant, n on - target organism data requirements for this product were waived on the basis that the guideline studies wer e not applicable because the proposed registration will only

permit indoor use

. Thus, non

- target t oxicity is not anticipated because of lack of exposure

. Based on its non

- target assessment, EPA has determined that the proposed registered use of cellulose i n 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 irritatio n . 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 cellul ose 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 Sy

mbol 84889

- R) and the EP (EPA File Sy mbol 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 adequatel y 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**Cellulose**

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6 resid ential 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 acti ve 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 id entification (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 , i t 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 product s, PCC 38
- DD (EPA File Sy mbol No. 8 4889
- R) and Rode

- Trol (EPA File S ymbol No. 8 4889
- E ) co ntainin g 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 o n February 29, 2012 (7 7 FR 12296 )

. No comments were received following this publ ication

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

.**Cellulose**

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7 **B. F**  **ood 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** Pow d ered 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 consequentl y 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 poly saccharide, 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 microcry stalline cellulose are approved b y 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 re quirement 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 c orn 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 analy ses 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 microcry stalline 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**Cellulose**

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8 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 suppo rt 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 microcry stalline cellulose. Microcry stalline cellulose is purifie d, partially depoly merized 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 likel y to result in repeat oral exposure to humans. The p roposed product is intended for use to formulate EPs which will be used as rod enticides 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 c ellulose 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 microcry stalline c ellu lose

. In their safety evaluation of microcrystalline cellulose, the WHO reviewed these studies and concluded that there is no evidence to indicate that consumption of microcry stalline cellulose in foods (when foods are produced according to good manufa cturing processes) will result in toxic effects in humans ( MRID 48433405, p. 25 of**Cellulose**

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9 100). Moreover, humans are already naturall y 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 expec ted to be metabolized differently by the dermal route of exposure than by the oral route and the metabolite is of toxicological concern. P urposeful application and prolonged exposure to the human skin is not anticipated based on the use pattern of the prop osed product (the product will be placed in bait stations and/or tray s 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 ro ute 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 phy sical properties of the active ingredient , wh ich is a solid. The proposed EP is formulated as a pellet th at 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 tray s.
**c .**  **Developmental Toxicity** Developmental toxicity

data ar e 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 co ntaining the active ingredient (the product will be placed in bait stations and/or tray s and left alone to attract rodents)

. If used according to label instructions, significant oral, dermal and inhalation exposure to the active ingredient is not anticipat ed. N o 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 structurall y related to a known mutagen or belong to any chemical class of compounds containing a known mutagen.**Cellulose**

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10 Significant human exposure is unlikely based on the use pattern (the proposed EP will be placed in bait stations or in tray s and left alone to attract rodents). Additionally , the proposed EP is for nonfood

- uses onl y. Moreover, in studies reviewed by the WHO, microcry stalline cellulose was not mutagenic in v arious in vitro mutagenicity assays in Salmonella typhimurium and Escherichia coli and it was not mutagenic in in vivo mouse ery throcy te micronucleus mutagenicity

as say s.
**e .**  **Companion Animal/Nontarget Animal Toxicity and Risk Characterization** T o 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 ( Fe lis 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 day s. 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 ty pically 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 patholo gy 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 day s post - applic ation (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 produc t 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 o f 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 n o toxicolog ical endpoints were identified for this active ingredient , a dose respon se assessment was not required.**Cellulose**

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11 **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 onl y; therefore, cellulose residues in drinking water are unlikely

. **4 .**  **Occupational, R esidential, 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 tray s (which limits exposure) and is not likely to be directly handled when used in accordance with l abel 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 tray s 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 pre sents 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 ris k to humans. No relevant toxicological endpoints were identified and significant exposure is not expected if label instruction s are followed. Any exposure in residential, school and/or day care settings is likel y 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 di et 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 anti cipated 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.**Cellulose**

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12 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, wi ll result from the use of this chemical when label instructions are followed. **C. E**  **nvironmental Assessment 1**  **. Ecological Hazards**  All non - target toxicology data requirements have b een satisfied in accordance with 40 CFR 158.206 0

. 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 t o 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 ri sk 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” feder ally

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 .**  **E fficacy Data**  Data and i nformation i n 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 day s for rats and 3 day s 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 phys ical disruption of the feeding mechanism in rats and mice. Mortality is caused by

deh ydration and**Cellulose**

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13 malnutrition . S everal postulated pathological pathway s were investigated and non e were established as the phys iological 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 feedin g 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 accuratel y reflect the conditions of testing. Product performance data directl y 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 appl yi ng the bait stations or tray s, 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 warrant s proposed claims; (B) its labeling and other materials compl y with the requirements of FIFRA; (C) it will perform its intended functi on 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 b y the science assessments supporting the end use product containing the manufacturing use product, cellulose

. The end use product is not expected to cau se unreasonable adverse effects

. Theref ore, 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, an d 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**Cellulose**

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14 environmental justice issues, please visit EPA’s website at http://www.epa.gov/compliance/environmentaljustice/index.html

. **V I**  **. 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. R eporting 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 hy persensitivity

(including both suspected and confirmed incidents) must be reported to the Agency under the provisions of 40 CFR Part 158.2050(d). **VI I**  **. A**  **PPENDIX 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 im purities 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**Cellulose**

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15 **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 Phy sical State Solid 48433402 830.6304 Odor Faintly sweet 48433402 830.6313 Stability to Normal and

E levated Tem

peratures, Metals and Metal I ons 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**Cellulose**

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16

**Table 3 . Mam**  **malian 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) LD 50 > 3160 mg/kg 1 ,3 (males) LD 50 > 5000 mg/kg 2 ,3 (females and males) IV 48433405 48534101 Acute dermal toxicity (rat) (870.1200) LD 50 > 2 000 mg/kg 2 ,3 (females and males) III 48433405 4853410 2 Acute inhalation toxicity (rat) (870.1300) LC 50 > 5.35 mg/L 2,3 (females and males) IV 48433405 4853410 3 Primary eye irritation (rabbit) (870.2400) Minimally irritating 2 IV 48433405 4853410 4 Primary dermal irritation (rabbit) (870.2500) Nonirritating 2 IV 48433405 Dermal sensitization (guinea pig) (870.2600) Not a sensitizer2 N/A 48433405 4853410 5

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 re view 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 4853410 6

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 ).**Cellulose**

**Page 17**  **of 19**  **Biopesticides Registration Action Document**

17

**Table 3 . Mam**  **malian Toxicology Data for Powdered Corn Cobs (Cellulose)**  **(40 CFR § 158.2050) Study/OCSPP Guideline No.**  **Results Toxicity**  **Category/Description MRID** 

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 4853410 8

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. I n vivo mouse erythrocyte micronucleus mutagenicity assays using microcrystalline cellulose were reviewed by the WHO . All results were negative for genotoxicity. 48433405 4853410 8

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 cel lulose r eviewed by the WHO

. 48433405 4853410 7

1 Test substance was refined alpha

- cellulose. 2 Test substance was 85% microcrystalline cellulose. 3 Highest dose tested.**Cellulose**

**Page 18**  **of 19**  **Biopesticides Registration Action Document**

18 **VIII. A**  **PPENDIX B.**  **For product specific information, please refer to**  **http://www.epa.gov/pesticides/pestlabels .**  **IX .**  **A PPENDIX**  **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 L eonard 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. 20 12 . 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. a ctive i ngredient 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 EC 50 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**Cellulose**

**Page 19**  **of 19**  **Biopesticides Registration Action Document**

19 FFDCA Federal Food, Drug, and Cosmetic Ac t 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 LC 50 median lethal concentration. A statistic ally 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)

. LD 50 me dian 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” NI OSH 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 O CSPP 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