1 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 pestic ide 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 a ggregate exposure to the pesticide chemical residue, including all anticipated dietary expo sures and all other exposures for wh ich there is reliable information.” This includes exposure through drinking water and in residential settings but does not include occupational exposure. Pursuant to FFDCA secti on 408(c)(2)(B), in establishing or ma intaining 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 cons ideration to exposure of in fants 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 in fants and children from aggregate exposure to the pesticide chemical residue . . . .” Additionally, FFDC A section 408(b)(2)(D) requires that the EPA consider “available information concerning the cu mulative effects of [a particular pe sticide's] . . . residues and other substances that have a comm on mechanism of toxicity.”

The EPA performs a number of analyses to determin e 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 fi ling of a pesticide tole rance petition (PP 4F8336) by BASF Corporation, 26 Davis Dr. Research Triang le 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 residue s 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 ava ilable 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 an alysis was repeated more recently with additional strains, it was de termined that strain MBI600 more closely matched strains other than2 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 pect inase or pectinolytic enzymes, and it is able to grow at pH 9.5. Thes e characteristics further distinguish Bacillus amyl oliquefaciens strains from Bacillus subtilis strains. Based on this information and the ge netic analysis of closely related taxa of the Bacillus subtilis group, including stra in 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, availabl e 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 ava ilable 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 re lationship of this information to human risk. The petitioner submitted no additional toxi cology 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 lite rature which confirmed that the propos ed change to the species name is appropriate and found no new toxicol ogical concerns. The EPA also considered available information concerning the variability of the se nsitivities of major identifiable subgroups of consumers, including infants and children. The EPA conclude d that the name change does not af fect the toxicological profile or safety conclusions reached in EPA’s review of the tolerance petition for Bacillus subtilis strain MBI600, available at Docket ID Nu mber EPA-HQ-OPP-2008-0762-004 via http://www.regulations.gov

. IV. Aggregate Exposure

In examining aggregate exposure, FFDCA section 408 di rects the EPA to consider available information concerning exposures from the pest icide residue in food and all other non-occupational exposures, including drinking water from ground water or su rface water and exposure through pesticide use in gardens, lawns, or buildings (resi dential and other indoor uses).

The EPA determined that the name change does not a ffect the conclusions rega rding aggregate exposure, including food exposure, drinking water exposure, a nd other non-occupation e xposure reached in EPA’s review of the tolerance pe tition referenced above.

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

Section 408(b)(2)(D)(v) of FFDCA requi res that, when considering whethe r 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.”3 The EPA determined that the name change does not a ffect the conclusions regarding cumulative effects, including common mechanisms of toxicity or toxic meta bolites that the EPA reached in the review of the original tolerance petition. These conclusions ar e set forth in the documents cited above.

For information regarding the EPA’s efforts to dete rmine 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 th e U.S. population, including infants and children, from aggregate exposure to these residues.

B. Infants and Children

FFDCA section 408(b)(2)(C) pr ovides that the EPA shall apply an additional tenfold (10X) margin of safety for infants and children in th e 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 f actor when reliable data available to the EPA support the choi ce of a different factor. The EPA determined that the name change does not affect the determination that no additional marg in of safety is necessary to protect infants and children.

VII. Conclusions

The EPA concludes that the name ch ange does not affect the determina tion there is a r easonable certainty that no harm will result to the U.S. population, includi ng infants and children, from aggregate exposure to these residues. Therefore, the existing exemption fr om 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 containi ng 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

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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 strain s DSM7 and FZB42: a proposal for Bacillus amyloliquefaciens subsp. amyloliquefaciens sub nov and Bacillus amyloliquefaciens subsp. plantarum4 supsp. nov. based on complete genome sequence compar isons. Internation Journal of Systematic and Evolutionary Microbiology 61:1786-1801.