Document ID: EPA-HQ-OPP-2014-0560-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2014-10-24T04:00Z

<EPA BIOPESTICIDES AND POLLUTION PREVENTION DIVISION COMPANY NOTICE OF
FILING FOR PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER  

<EPA Biopesticides and Pollution Prevention Division contact: Kimberly
Nesci, 703-308-8059>

 

<SUBMISSION: E-mail the completed template to: nesci.kimberly@epa.gov.>

<TEMPLATE:>

<Andermatt Biocontrol AG>

<PP3F8221

>

<	EPA has received a pesticide petition (3F8221) from Andermatt
Biocontrol AG, Stahlermatten, 6 CH-6146, Grossdietwil, Switzerland
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.>

<(Options (pick one)>

<	2. to establish an exemption from the requirement of a tolerance for
Bacillus amyloliquefaciens strain FZB42

<(Options (pick one)>

	1. microbial pesticide for Bacillus amyloliquefaciens strain FZB42

<Pursuant to section 408(d)(2)(A)(i) of  FFDCA, as amended, Andermatt
Biocontrol AG has submitted the following summary of information, data,
and arguments in support of their pesticide petition. This summary was
prepared by SciReg, Inc. and EPA has not fully evaluated the merits of
the pesticide petition. The summary may have been edited by 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 position and not the position of the
petitioner.>

<I. Andermatt Biocontrol AG Petition Summary>

	3F8221

<A. Product Name and Proposed Use Practices>

<	RhizoVital 42 containing Bacillus amyloliquefaciens strain FZB42 is
being submitted to EPA for registration. It will be applied for
preventive use against major soil-borne diseases on most crops.
Application rates are projected to be up to 28 fl. oz./acre/application;
up to three applications per season are anticipated

>

<B. Product Identity/Chemistry>

<	1. Identity of the pesticide and corresponding residues. 

Kingdom:	Bacteria

Phylum:	Firmicutes

Class:		Bacilli

Order:		Bacillales

Family:	Bacillaceae

Genus:	Bacillus

Species:	B. amyloliquefaciens (Gram-positive)

Bacillus amyloliquefaciens is a naturally-occurring, ubiquitous soil
microbe. 

Bacillus amyloliquefaciens strain FZB42 was isolated in Germany from
naturally-infected soil. It is not genetically modified. Bacillus
amyloliquefaciens strain FZB42 is intended for preventive use against
major soil-borne diseases on a variety of crops, ornamental plants, and
turf.

<	2. Magnitude of residues at the time of harvest and method used to
determine the residue. No magnitude of residue (MOR) studies have been
conducted with Bacillus amyloliquefaciens strain FZB42 based on the low
toxicity of the active ingredient (see Toxicological Profile). OPPTS
Guideline 885.2000, section f, Background for Residue Analysis of
Microbial Pest Control Agents (MPCA), states: 

“The Agency evaluates residue data for MPCAs used on food, feed, or
raw agricultural commodities only if toxic or other harmful properties
were observed in the maximum hazard toxicology tests (Tier I) prescribed
in toxicology test guidelines OPPTS 885.3050 through 885.3650 of this
series. If Tier I toxicology tests indicate no toxic or other harmful
properties, then no residue data (with the general exception of a
monitoring method) would be indicated and thus a recommendation for an
exemption from the requirements of a tolerance can be made.”>

<	3. A statement of why an analytical method of detecting and measuring
the levels of the pesticide residue are not needed. While Bacillus
amyloliquefaciens strain FZB42 residues may be present on treated
food/feed commodities, based on the submitted toxicology data, Bacillus
amyloliquefaciens strain FZB42 is virtually non-toxic and is not
pathogenic. Andermatt Biocontrol AG is, therefore, submitting a petition
to establish an exemption from the requirement of a tolerance and an
analytical method is not required. >

<C. Mammalian Toxicological Profile>

<	The full reports that support this petition and which are summarized
in this section were previously submitted to the Agency by Andermatt
Biocontrol AG in support of registration. Based on the data submitted,
it is established that Bacillus amyloliquefaciens strain FZB42 is
neither toxic, nor pathogenic to humans. 

Acute Oral Toxicity/Pathogenicity: 

Twenty-four male and 24 female Sprague-Dawley rats were dosed at 5.7x109
CFU/mL of B. amyloliquefaciens strain FZB42. Interim sacrifices were
made on three animals per sex on Days 3, 7, and 14; the remaining
animals were sacrificed on Day 21, the termination of the study. There
were no deaths and all animals appeared normal throughout the entire
study. 

Feces and urine samples were collected at 1, 24, 48 and 72 hours and Day
14. Blood, brain, lung, liver, kidney, spleen, lymph nodes, and cecum
content were evaluated on Days 3, 7, 14, and 21 (all other tissues) for
test article-treated animals, untreated control animals, and inactivated
test article-treated animals). By 24 hours after dosing, the test
substance appeared to have cleared from the urine. By Day 14, the test
substance showed a pattern of clearance from the feces.

A mycological summary of these evaluations follows.

Feces samples CFU/g

1 hr	24 hr	48 hr 	72 hr 	Day 14 

1.1 x 103	7.1 x 104	7.9 x 102	5.1 x 102	5.6 x 101

Urine samples CFU/g

1 hr	24 hr	48 hr 	72 hr 	Day 14 

6.1 x 102	0	0	0	0

Blood: All samples negative for B. amyloliquefaciens

Brain: All samples negative for B. amyloliquefaciens

Lung: All samples negative for B. amyloliquefaciens

Liver: All samples negative for B. amyloliquefaciens

Kidney: All samples negative for B. amyloliquefaciens 

Spleen: All samples negative for B. amyloliquefaciens

Lymph nodes: All samples negative for B. amyloliquefaciens

Cecum: All samples negative for B. amyloliquefaciens

Acute Dermal Toxicity: 

Ten animals were dosed at 5,000 mg/kg of RhizoVital 42 containing
4.1x1010 CFU/g of B. amyloliquefaciens strain FZB42. No skin reactions
or signs of toxicity were observed. All animals appeared healthy at
necropsy. The LD50 was determined to be greater than 5,000 mg/kg.

Acute Pulmonary Toxicity/Pathogenicity: 

Thirty-two male and 32 female Sprague-Dawley rats were assigned as
follows:

5 animals/sex - Group I, Untreated

4 animals/sex - Group II, Shelf Control

5 animals/sex - Group III, Inactive

18 animals/sex – Group IV, Microbial Pest Control Agent (MPCA)

Treated animals were dosed with 1.1x109 CFU/rat of RhizoVital 42.
Interim sacrifices were made on three animals per sex on Days 0 (3 hours
post-application), 3, 7, and 14; the remaining animals were sacrificed
on Day 21, the termination of the study. 

There were no deaths and there were no clinical signs noted in any
animal of any group.

Blood, brain, lung, liver, kidney, spleen, cecum contents, and
mesenteric lymph nodes were evaluated on Day 0 (feces only) and Day 3,
7, 14, and 21 (all other tissues) for all animals. A mycological summary
of these evaluations follows.

Blood: All samples negative for B. amyloliquefaciens

Brain: All samples negative for B. amyloliquefaciens

Lung: All samples negative for B. amyloliquefaciens, except for one
female on Day 3

Liver: All samples negative for B. amyloliquefaciens

Kidney: All samples negative for B. amyloliquefaciens

Spleen: All samples negative for B. amyloliquefaciens, except for one
male on Day 3

Mesenteric Lymph nodes: All samples negative for B. amyloliquefaciens

Cecum contents: All samples negative for B. amyloliquefaciens

Eye Irritation: 

Three rabbits were dosed with 0.1 mL (4.1x1010 CFU/g) of RhizoVital 42.
No irritation or other clinical signs were observed. RhizoVital 42 is
considered to be non-irritating.

Dermal Irritation: 

Three rabbits were each dosed with a semi-occlusive liquid patch of 0.5
mL of RhizoVital 42 for 4 hours. The test substance contained containing
4.1x1010  CFU/g of B. amyloliquefaciens strain FZB42. Grade 1 erythema
was observed in all animals 60 minutes after patch removal. No clinical
signs were observed 2 hours after patch removal. RhizoVital 42 is
considered to be virtually non-irritating.

Hypersensitivity Incidents: 

No reports of hypersensitivity have been associated with Bacillus
amyloliquefaciens strain FZB42.>

Acute Intravenous Toxicity/Pathogenicity:

Twenty-five male and 25 female Sprague Dawley rats were assigned as
follows: 

5 animals/sex - Group I, Untreated

5 animals/sex - Group II, Inactive MPCA

15 animals/sex - Group III, MPCA

Group II and Group III animals were dosed with 0.1 mL of RhizoVital 42
intravenously via tail vein. The suspension was prepared so as to
contain 3.0x109 CFU/rat. Interim sacrifices were made on three animals
per sex on Days 3, 7, 14 and 21; the remaining animals were sacrificed
on Day 28, the termination of the study. There were no deaths and there
were no clinical signs noted in any animal of any group.

Blood, brain, lung, liver, kidney, spleen, cecum contents, and
mesenteric lymph nodes were evaluated on Day 0 (blood only) and Day 3,
7, 14, and 21 (all other tissues) for MPCA treated animals. A
mycological summary of these evaluations follows.

Blood: By Day 3, the test substance showed a pattern of clearance. All
samples negative for B. amyloliquefaciens on Day 21.

Brain: By Day 14, the test substance showed a pattern of clearance. All
samples negative for B. amyloliquefaciens on Day 21.

Lung: On Day 21, all samples were negative for B. amyloliquefaciens
except for one male.

Liver: By Day 21, the test substance showed a pattern of clearance.

Kidney: By Day 21, the test substance showed a pattern of clearance.

Spleen: By Day 21, the test substance showed a pattern of clearance.

Mesenteric lymph nodes: By Day 21, the test substance showed a pattern
of clearance.

Cecum contents: By Day 21, the test substance showed a pattern of
clearance.

<D. Aggregate Exposure>

The potential for non-occupational, dietary, and non-dietary exposure to
Bacillus amyloliquefaciens strain FZB42 by the general population,
including infants and children, is likely through ingestion of treated
crops. 

<	1. Dietary exposure. 

<	i. Food. Dietary exposure to Bacillus amyloliquefaciens strain FZB42
should not be of concern due to the low toxicity shown across the entire
toxicological profile (see above).>

<	ii. Drinking water. Bacillus amyloliquefaciens is not likely to be
present in aquatic environments at significant levels, since it is not
known to inhabit such environments. Anticipated agricultural practice
prohibits direct application of the end-use product directly to water
and natural environmental filtration processes, such as soil and
vegetation, further limit aquatic exposure. Additionally, the label
requires the product to be immediately watered in after application, so
that the microbes are able reach the root zones of the target plants.>

<	2. Non-dietary exposure. Non-dietary exposure to Bacillus
amyloliquefaciens strain FZB42 will be much more likely through handling
by formulators and applicators, but in light of the subject strain’s
toxicological profile, should be of little concern. Although the
organism is ubiquitous, levels of exposure in broad segments of the
world’s population has not resulted in any significant reported
adverse effects.>

<E. Cumulative Effects>

<	Section 408(b)(2) of the FFDCA requires that, when considering whether
to establish an exemption from a tolerance, the Agency consider
available information concerning the cumulative effects of the
particular ingredient’s residues and other substances that have a
common mechanism of toxicity. These considerations include the possible
cumulative effects of such residues on infants and children. Bacillus
species are naturally-occurring, ubiquitous soil microbes. Bacillus
amyloliquefaciens strain FZB42 is neither toxic, nor pathogenic. The
end-use product, RhizoVital 42, is used preventively against major
soil-borne diseases on most crops through suppressive action. This
passive mode of action does not have a common chemical-based mechanism
of toxicity as can sometimes be found with typical organic chemicals.>

<F. Safety Determination>

<	1. U.S. population. Bacillus amyloliquefaciens strain FZB42 exhibits
low mammalian toxicity/pathogenicity, as demonstrated by the submitted
toxicology studies and summarized in the toxicological ical profile.
When Bacillus amyloliquefaciens strain FZB42 is used on raw agricultural
commodities in accordance with good agricultural practice, it meets the
reasonable certainty of no harm requirement.>

<	2. Infants and children. It is believed that the potential exposure of
infants and children to residues of Bacillus amyloliquefaciens strain
FZB42 through their use to protect crops from diseases is no greater
than that of the general population. Available information does not
suggest that infants and children are more susceptible to Bacillus
amyloliquefaciens strain FZB42 than are adults.>

<G. Effects on the Immune and Endocrine Systems>

<	Extensive literature searches and review of the Bacillus
amyloliquefaciens strain FZB42 toxicity/pathogenicity data indicate
there is no evidence that this strain is an endocrine disruptor or that
it has any known effect on immune systems.>

<H. Existing Tolerances>

<	There are no known agricultural tolerances or tolerance exemptions for
Bacillus amyloliquefaciens strain FZB42.>

<I. International Tolerances>

<	There are no known international tolerances for Bacillus
amyloliquefaciens strain FZB42.>

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