**T ITLE**  

### P **ETITION FOR A N**  

### E **XEMPTION FROM THE** 

### R**EQUIREMENT OF A** 

### T **OLERANCE FOR** 

### S **PODOPTERA FRUGIPERDA** 

### M**ULTIPLE** 

### N**UCLEOPOLYHEDROVIRUS** 

### – **3AP2**

**N OTICE OF**  

### F **ILING A** **UTHORS Susan MacIntosh**  **MacIntosh & Associates, Inc. 1203 Hartford Avenue**  **Saint Paul, MN 55116**

**T ES**  **T G** **UIDELINE Not Applicable**  **C OMPLETED**  **O N**  **April 29 , 2015** 
**S PONSOR**  **AgBiTech Pty Ltd**

**T ESTING**  **F ACILITY**  **Not Applicable** Total Number of Pages: 10

1 of 82 of 8



### STATEMENT OF **NO DATA CONFIDENTIALITY CLAIMS**  Compound: Spodoptera frugiperda Multiple Nucleopoly h edrovirus Title: **P ETITION FOR AN**  **E XEMPTION FROM THE**  **R EQUIREMENT OF A**  **T OLERANCE FOR**  **S PODOPTERA FRUGIPERDA**  **M ULTIPLE**  **N UCLEOPOLYHEDROVIRUS**  **– 3AP2**  **N OTICE OF**  **F ILING**  No claim of confidentiality is made for any information contained in this study on the basis of its falling within the scope of FIFRA §10(d)(1)(A), (B), or (C). Company : AgBiTech Pty Ltd 8 Rocla Court Glenvale, Queensland, 4350 Australia

Company Agent: Date : April 29, 2015

Susan MacIntosh President MacIntosh & Associ ates, Inc. Regulatory Agent On behalf of Pasteuria Bioscience, Inc.3 of 8



### GOOD LABORATORY PRACTICE COMPLIANCE STATEMENT This study

was not conducted in accordance with the requirements for the U.S. EPA Good Laboratory

Practice (GLP) Standards, 40 CFR 160, 1989.

Study Director 29 April 2015

Susan MacIntosh Date Regulatory Agent to AgBiTech

Sponsor 29 April 2015

Anthony Hawes Date CEO

Submitter 29 April 2015

Susan MacIntosh Date Regulatory Agent to AgBiTech4 of 8 

### APPROVALS PAGE We, the undersigned, declare that this report accurately represents the results observed during the course of this study
.
Study Director/Author 29 April 2015

Susan MacIntosh Date Agent on behalf of AgBiTech

Co
-Author 29 April 2015 Anthony Hawes Date CEO, AgBiTech5 of 8

**EPA BIOPESTICIDES AND POLLUTION PREVENTION DIVISION COMPANY NOTICE OF FI** **LING FOR PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER**  **EPA Biopesticides and Pollution Prevention Division contact: Robert McNally, 703**  **- 308**  **- 8085** 
MacIntosh and Associates, Inc, 1203 Hartford Avenue, St. Paul, MN 55116
- 1622, on behalf of AgBiT ech Pty

Ltd , 8 Rocla Court , Glenvale, Queensland, 4350 , Australia **5F8361** EPA has received a pesticide petition **( 5F**  **8361 )**  from MacIntosh and Associates, Inc, 1203 Hartford Avenue, St. Paul, MN 55116
- 1622, on behalf of AgBiTech Pty Ltd, 8 Rocla Court; Glenvale, Queensland, 4350 , Australia proposing, pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180 to establish an exemption from the requirement of a tolerance for microbial pesticide S

podoptera frugiperda Multiple Nucleopolyhedrovirus

– 3AP2 [SD
6840 ]
. Pursuant to section 408(d)(2)(A)(i) of FFDCA, as amended, **MacIntosh and Associates, Inc, 1203 Hartford Avenue, St. Paul, MN 55116**  **- 1622, on behalf of**  AgBiTech Pty Ltd has submitted the f

ollowing summary

of information, data, and arguments in support of their pesticide petition. This summary was prepared by **MacIntosh and Associates, Inc, 1203 Hartford Avenue, St. Paul, MN 55116**  **- 1622, on behalf of**  AgBiTech Pty Ltd and EPA has not fully

evaluated the merits of the pesticide petition. The summary may have been edited b y EPA if the terminology used was unclear, the summary contained extraneous material, or the summary unintentionally

made the reader conclude that the findings reflected EPA’s po sition and not the position of the petitioner. **I.** MacIntosh and Associates, Inc, 1203 Hartford Avenue, St. Paul, MN 55116
- 1622, on behalf of AgBiTech Pty

Ltd **Petition Summary 5F8361**  A. Product Name and Proposed Use Practices Spodoptera frugiperda Mulit ple Nucleopoly

hedrovirus (SfMNPV) is a baculovirus characterized by

rod
- like nucleocapsids contained within a viral envelope. Baculoviridae genomes are supercoiled circular double stranded DNA ranging from 90
- 230 kbp in size. Baculoviruses are ancient organisms, likely discovered as early as 5000 years ago as a disease impacting the silk industry in Asia. They

have been exclusively isolated from6 of 8

arthropods, specifically from Lepidoptera, Hy menoptera and Diptera, and usuall y identified by

the species that they

infect along with the ty

pe of occlusion body

that they form. SfMNPV has a relatively narrow host range specific for Noctui dae Lepidoptera. The target pests are Spodoptera frugiperda and Spodoptera exigua. SfMNPV and NPVs in general are ubiquitous in nature, found in nearly every l ocation where investigated. This natural product will be an excellent addition to growers’ options for Spodoptera spp. control that reduces or eliminates the need for chemical inputs and fits well within an integrated pest management program for organic or conventional production. B. Product Identity/Chemistry 1. Identity of the pesticide and corresponding residues. The insect viral strain, Spodoptera frugiperda Multiple Nucleopoly hedrovirus

– 3AP2 [SD
- 6840 ] was isolated from insect cadavers collected in Missouri (USA)
. The strain is a natural insect viral strain that has not been modified in any w ay and is identical to SfMNPV that are ubiquitous in nature. NPVs are known for their ability to control their Spodoptera spp. hosts and have been shown to reduce larval damage below economic levels leading to improved crop production. 2. Magnitude of residues at the time of harvest and method used to determine the residue
. NA
. S ee 1. Above
. 3. A statement of why an analytical m ethod of detecting and measuring the levels of the pesticide residue are not needed. No analy tical method is included since this petition requests an exemption from the requirement of a tolerance. C. Mammalian Toxicological Profile Baculoviruses in general have a long history o f safe use as microbial pesticides in the USA. Baculoviruses have narrow host ranges and virtually no adverse effects in people, wi ldlife, or non-target insects. The active ingredient for all baculoviruses, including SfMNPV, is the occlusion bodies (OBs) that are formed in the nuclei of infected cells. Target larvae ingest OBs and until about day 4 post
- infection, no sy

mptoms are observed. From 4
- 6 days post- infection, the larvae begin to appear diseased and ty pically stop eating at day

6
- 7 with death occurring between 7 - 10 days post- infection. This mode
- of
action occurs across all baculoviruses demonstrating the similarity of this group of insect control viruses. The body o f toxicology

data is quite extensive for NPVs, addressing di fferent routes of exposure – oral, pulmonary, dermal and injection

– with many different species, rodents, dogs, monkeys and even humans for Helicoverpa zea NPV (EPA, 1990)
. Since the reregistration actions completed in 1990, other NPV and GV strains have been registered, beet ar my worm, Indian Meal Moth, etc. Inaddition, a full set of toxicology results are available from other less related NPVs (e.g., OpNPV, Ld NPV) addressing the same7 of 8

routes of exposure but limited to rodent and a dog study. The last re -registration documents prepared by EPA that provide detailed historical regulatory

data and extensive review of health and safety data on NPVs were published in 1990s (EPA, 1990; EPA, 1996). The full body of toxicology data regardless of the baculovirus species is important to cite given the close relatedness of all baculoviruses and their common mode of action ( see Figure 2, Harrison et al., 2008). An extensive genetic analys is of all open reading frames of the SfMNPV as compared to SeMNPV and other related insect viruses, demonstrates that these two Spodoptera spp. MNPVs are very s imilar
. However they

are different species. What makes each strain unique is the pest complex that they

control. Perhaps one of the best description of the lack of human tox icity is provided in by

O ECD (2002): ‘ Baculoviruses are naturally occurring pathogens of arthropods. Their host range is exclusively restricted to arthropods. No member of this virus family is infective to plants or vertebrates. Baculoviruses are ubiquitousl

y resent in the environment and have been used for biological insect control for more than 100 years. Circumstantial evidence for the safety of baculoviruses emerges from the history of contact between baculoviruses and humans without any detrimental effec t.’ As part of the scientific rationale a bridging study was conducted using mammalian cell lines to characterize any mammalian cell effects from SfMNPV
. Non- occluded SfMNPV isolates , control insect medium (NPV control), spent medium, inactivated virus as appropriate and a commercial H. zea NPV product were included in the tests
. Inthis study, no cy

topathic effects or replication of SfMNPV exposed to any o f the mammalian cell lines were observed. If NPV nucleic acid had been detected in the cells, then viral antigen would have been assayed; and, the presence of infectious virus in the supernatant at the same days of incubation would also have been assayed in a sensitive insect bioassay . However, since no SfMNPV nucleic acid was detected, no further testing was necessary . The results of this cell culture study, demonstrating a total lack of infectivity or toxicity of SfMNPV to mammalian cells, allows for a bridge to the many different ty pes of mammalian toxicology

s tudies conducted with commercial NPV strains
. The common mode of action shared by all NPV adds to the weight of evidence that NPVs as a group , and specifically

S fMNPV , will not cause mammalian toxicity
. Therefore, SfMNPV should be considered as safe as any baculovirus used in past and current commercial end products. D. Aggregate Exposure 1. Dietary exposure. Since SfMNPV is applied to the crop , there will be negligible to non- existent dietary, dermal or inhalation exposure. Use of this baculovirus8 of 8

in pesticide products will not increase the exposure of humans beyond normal background levels. i. Food. There will be no accumulation of the insect virus or this SfMNPV product in any plant tissues or food. ii. Drinking water. Drinking water is unlikely to be contaminated with SfMNPV , becau se SfMNPV onl y grows and replicates within it’s Spodoptera spp. host , which are limited to plant and soil habitats and do not live in water environments. 2. Non
- dietary exposure . Non- dietary exposure of infants, children or the US population in general, to SfMNPV are not expected due to the uses of this product within agricultural settings. E. Cumulative Effects The unique mode
- of

- action and narrow host range SfMNPV , and of NPV occlusion bodies in general , coupled with the lack of mammalian toxicity provides no basis for the expectation of cumulative exposure with other compounds. F . Safety Determination 1. U.S. population. The lack of mammalian toxicity to the insect virus SfMNPV provides support for our request of an exemption from the requirement o f a tolerance set forth in this petition, including infants and children. 2. Infants and children
. (See F.1. above) G. Effects on the Immune and Endocrine Systems The unique mode
- of

- action and narrow host range SfMNPV , and of NPV occlusion bodies in general , coupled with the lack of mammalian toxicity provides no basis for the expectation of effects on the immune or endocrine systems. H. Existing Tolerances No tolerances or tolerance exemptions have been granted for SfMNPV
. However, these naturally o ccurring insect viruses have all been granted exemptions from the requirement of a tolerance; Heliocoverpa zea NPV (§180.1027), Spodoptera exigua NPV (§180.1118), Anagrapha falcifera MNPV (§180.1149) and Cydia pomenella GV (§180.1148) and Indian Meal Moth GV (§180.1218). I . International Tolerances No international tolerances or tolerance exemptions have been granted for SfMNPV
.