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Federal Food, Drug, and Cosmetic Act (FFDCA) Considerations for Bacillus amyloliquefaciens strain 

MBI600 

Docket ID Number: EPA-HQ-OPP-2008-0762 

Date: October 5, 2015 

Section 408(c)(2)(A)(i) of FFDCA allows the EPA to establish an exemption from the requirement for a 

tolerance (the legal limit for a pesticide chemical residue in or on a food) only if the EPA determines that 

the exemption is “safe.” Section 408(c)(2)(A)(ii) of FFDCA defines “safe” to mean that “there is a 

reasonable certainty that no harm will result from aggregate exposure to the pesticide chemical residue, 

including all anticipated dietary exposures and all other exposures for which there is reliable information.” 

This includes exposure through drinking water and in residential settings but does not include occupational 

exposure. Pursuant to FFDCA section 408(c)(2)(B), in establishing or maintaining in effect an exemption 

from the requirement of a tolerance, the EPA must take into account the factors set forth in FFDCA section 

408(b)(2)(C), which require the EPA to give special consideration to exposure of infants and children to the 

pesticide chemical residue in establishing a tolerance or tolerance exemption, and to “ensure that there is a 

reasonable certainty that no harm will result to infants and children from aggregate exposure to the 

pesticide chemical residue . . . .” Additionally, FFDCA section 408(b)(2)(D) requires that the EPA consider 

“available information concerning the cumulative effects of [a particular pesticide's] . . . residues and other 

substances that have a common mechanism of toxicity.” 

The EPA performs a number of analyses to determine the risks from aggregate exposure to pesticide 

residues. First, the EPA determines the toxicity of the pesticide. Second, the EPA examines exposure to the 

pesticide through food, drinking water, and other exposures that occur as a result of pesticide use in 

residential settings. 

I. Summary of Petition for Tolerance Exemption

In the Federal Register of April 6, 2015, (80 FR18327), the EPA issued a notice pursuant to FFDCA 

section 408(d)(3), 21 U.S.C. 346a(d)(3), announcing the filing of a pesticide tolerance petition (PP 4F8336) 

by BASF Corporation, 26 Davis Dr. Research Triangle Park, NC 27709. The petition requested that 40 

CFR part 180.1128 be amended to change the species name to "amyloliquefaciens" and revising the 

tolerance exemption to state as follows: 

“40 CFR § 180.1128 Bacillus amyloliquefaciens MBI600; exemption form the requirement of a 

tolerance. An exemption from the requirement of a tolerance is established for residues of the 

biofungicide Bacillus amyloliquefaciens MBI600 (antecedent Bacillus subtilis MBI600) in or on all 

food commodities, including residues resulting from post-harvest uses, when applied or used in 

accordance with good agricultural practices.” 

A summary of the petition prepared by the petitioner BASF Corporation is available in Docket ID Number 

EPA-HQ-OPP-2008-0762-006 via http://www.regulations.gov. 

II. Active Ingredient Identity

Consistent with FFDCA section 408(b)(2)(D), the EPA reviewed the available scientific data and other 

relevant information on Bacillus amyloliquefaciens MBI600 (antecedent Bacillus subtilis MBI600). 

According to information submitted by BASF, when analyzed in 2009 and 2010, strain MBI600 appeared 

to match closely to other Bacillus subtilis strains. When this molecular analysis was repeated more recently 

with additional strains, it was determined that strain MBI600 more closely matched strains other than 
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Bacillus subtilis. In the reanalysis of the phylogenetic tree, based upon re-sequencing of the strain MBI600, the 

Strain was found to be more similar to Bacillus amyloliquefaciens than it is to Bacillus subtilis, and MBI600 

matched closely to strains that have all been recently re-classified as Bacillus amyloliquefaciens subsp. 

plantarum (Borriss et al., 2011). 

Additional analysis showed that Strain MBI600 is negative for pectinase or pectinolytic enzymes, 

and it is able to grow at pH 9.5. These characteristics further distinguish Bacillus amyloliquefaciens strains 

from Bacillus subtilis strains. Based on this information and the genetic analysis of closely related taxa of 

the Bacillus subtilis group, including strain MBI600, BASF proposed and the EPA confirmed that the strain 

is more similar to Bacillus amyloliquefaciens than it is to Bacillus subtilis. The EPA concluded that 

Bacillus subtilis strain MBI600 has been renamed according to the proper scientific nomenclature to 

Bacillus amyloliquefaciens strain MBI600. The name change does not affect the safety conclusions in 

EPA’s review of the tolerance petition for Bacillus subtilis strain MBI600, available at Docket ID Number 

EPA-HQ-OPP-2008-0762-004 via http://www.regulations.gov. 

III. Toxicological Profile 

Consistent with FFDCA section 408(b)(2)(D), the EPA reviewed the available scientific data and other 

relevant information on Bacillus amyloliquefaciens MBI600 (antecedent Bacillus subtilis MBI600), and 

considered its validity, completeness, and reliability, as well as the relationship of this information to 

human risk. The petitioner submitted no additional toxicology data, and EPA determined that no additional 

toxicology data were necessary to support the petition to change the name to B. amyloliquefaciens MBI600, 

since B. amyloliquefaciens MBI600 is the same microbial substance for which the Agency has already 

reviewed toxicology data, i.e., the microbial strain formerly called Bacillus subtilis MBI600. EPA also 

reviewed the published literature which confirmed that the proposed change to the species name is 

appropriate and found no new toxicological concerns. The EPA also considered available information 

concerning the variability of the sensitivities of major identifiable subgroups of consumers, including 

infants and children. The EPA concluded that the name change does not affect the toxicological profile or 

safety conclusions reached in EPA’s review of the tolerance petition for Bacillus subtilis strain MBI600, 

available at Docket ID Number EPA-HQ-OPP-2008-0762-004 via http://www.regulations.gov. 

IV. Aggregate Exposure 

In examining aggregate exposure, FFDCA section 408 directs the EPA to consider available information 

concerning exposures from the pesticide residue in food and all other non-occupational exposures, 

including drinking water from ground water or surface water and exposure through pesticide use in 

gardens, lawns, or buildings (residential and other indoor uses). 

The EPA determined that the name change does not affect the conclusions regarding aggregate exposure, 

including food exposure, drinking water exposure, and other non-occupation exposure reached in EPA’s 

review of the tolerance petition referenced above. 

V. Cumulative Effects from Substances with a Common Mechanism of Toxicity 

Section 408(b)(2)(D)(v) of FFDCA requires that, when considering whether to establish, modify, or revoke 

a tolerance, the EPA consider “available information concerning the cumulative effects of [a particular 

pesticide’s] . . . residues and other substances that have a common mechanism of toxicity.” 
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The EPA determined that the name change does not affect the conclusions regarding cumulative effects, 

including common mechanisms of toxicity or toxic metabolites that the EPA reached in the review of the 

original tolerance petition. These conclusions are set forth in the documents cited above. 

For information regarding the EPA’s efforts to determine chemicals that have a common mechanism of 

toxicity and to evaluate the cumulative effects of such chemicals, see the EPA’s website at 

http://www.epa.gov/pesticides/cumulative.

VI. Determination of Safety for the U.S. Population, Infants and Children 

A. U.S. Population 

The EPA determined that the name change does not affect EPA’s prior determination that there is 

reasonable certainty that no harm will result to the U.S. population, including infants and children, from 

aggregate exposure to these residues. 

B. Infants and Children 

FFDCA section 408(b)(2)(C) provides that the EPA shall apply an additional tenfold (10X) margin of 

safety for infants and children in the case of threshold effects to account for prenatal and postnatal toxicity 

and the completeness of the database on toxicity and exposure, unless the EPA determines based on reliable 

data that a different margin of safety will be safe for infants and children. This additional margin of safety 

is commonly referred to as the Food Quality Protection Act Safety Factor. In applying this provision, the 

EPA either retains the default value of 10X or uses a different additional safety factor when reliable data 

available to the EPA support the choice of a different factor. The EPA determined that the name change 

does not affect the determination that no additional margin of safety is necessary to protect infants and 

children. 

VII. Conclusions 

The EPA concludes that the name change does not affect the determination there is a reasonable certainty 

that no harm will result to the U.S. population, including infants and children, from aggregate exposure to 

these residues. Therefore, the existing exemption from the requirement of a tolerance for residues of 

Bacillus subtilis strain MBI600 is amended by changing the name to residues of Bacillus 

amyloliquefaciens strain MBI600 (antecedent Bacillus subtilis MBI600) in or on all food commodities, 

including residues resulting from post-harvest uses, when applied or used in accordance with good 

agricultural practices. 

VIII. References 

1. U.S. EPA. 2015. Review of petition to amend the exemption from the requirement of a tolerance for 

residues of products containing the active ingredient “Bacillus subtilis MBI600” at 40 CFR § 180.1128 to 

change the species designation to “Bacillus amyloliquefaciens MBI600”. Memorandum from K. Haymes, 

Ph,D. through John Kough, Ph.D. to Ann Sibold, dated May 15, 2015.

2. Borriss, R., Chen, X.-H., Ruckert, C., Blom, J., Becker, A., Baumgarth, B., Fan, B., Pukall, R., 

Schumann, P., Sproer, C., Junge, H., Vater, J., Puler, A., Klenk, H-P. 2011 Relationship of Bacillus 

amyloliquefaciens clades associated with strains DSM7 and FZB42: a proposal for Bacillus 

amyloliquefaciens subsp. amyloliquefaciens sub nov and Bacillus amyloliquefaciens subsp. plantarum 
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supsp. nov. based on complete genome sequence comparisons. Internation Journal of Systematic and 

Evolutionary Microbiology 61:1786-1801.