1 Federal Food, Drug, and Cosmetic Act (FFDCA) Considerations for Aureobasidium pullulans strains

DSM 14940 and DSM 14941

Docket ID Number: EPA

- HQ

- OPP

- 20 10

- 0099

Date: October 15, 2015

Section 408(c)(2)(A)(i) of FFDCA allows the U.S. Environmental Protection Agency ( 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

“sa fe” 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 include s 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, an d to “ensure that there is a reasonable certainty that no harm will result to infants and children from aggregate exposure to th e pesticide chemical residue . . . . ” Additionally, FFDCA section 408(b)(2)(D) requires that the EPA consider “available informa tion 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 fo od, drinking water, and other exposures that occur as a result of pesticide use in residential settings.

I. Summary of Petitioned

- for Ame ndment of Tolerance Exemption

In the Federal Register of July 17 , 2015 ( 80 FR 42462)

, 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 4F8342) by bio

- ferm GmbH, Technologiezentrum Tulln, Technopark 1, Tulln, 3430, Austria . The petition requested

that 40 CFR part 180 be amended by establishing an exemption from the requirement of a tolerance for

residues of Aureobasidium pullulans strains DSM 14940 and DSM 14941 in or on all food commodities.

Th at document referenced a summary of the petition prepared by the petitioner bio

- ferm GmbH , which is

available in D ocket ID Number EPA

- HQ

- OPP

- 20 10

- 0099 via http://www.regulations.gov

.

II

. Toxicological Profile

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

relevant information on Aureobasidium pullulans strains DSM 14940 and DSM 14941 , and considered its validity, completeness, and reliability, as well as the relationship of this information to human risk. The EPA also considered available information concerning the variability of the sensitivities of major identifiable subgroups of co nsumers, including infants and children.

A. Overview of Aureobasidium pullulans s trains DSM 14940 and DSM 14941

Aureobasidium pullulans is a ``yeast

- like'' saprophytic fungus found in the phyllosphere of many plants, and it has been isolated from soil and aquatic environments (Refs. 1, 2, and 3). It is commonly isolated from healthy grape (Refs. 4 and 5) and apple (Ref. 6) plants, as well as other plants (Refs. 7, 8, 9, 10, and 11). Although associated with disease in some plants, the fungus generally is recognized as a saprobe, since2 it derives its nourishment from nonliving or decaying organic matter, and is only considered a weak pathogen or parasite of certain plants (Refs. 2 and 12). It is a known antagonist of several plant disease

causing organisms, and is an important producer of enzymes for biotechnological and industrial applications (Ref. 1). Aureobasidium pullulans strains DSM 14940 and DSM 14941 were isolated from apple leaves and

classi fied by the German Strain Collection for Microorganisms (DSMZ). Neither is a mutant nor genetically modified strain and they are not closely related to toxigenic human pathogens. As discussed in

Pesticide Petition s (PP) 9F7623 and 4F8342) , product analysis data demonstrate that Aureobasidium pullulans strain DSM 14941 is closely related to strain DSM 14940. The two strains share many similar genetic and morphological characteristics. B ioferm GmbH has register ed two manufacturing

- use pesticide products (MPs) : `` Aureobasidium pullulans strain DSM 14941 Technical,'' and `` Aureobasidium pullulans strain DSM 14940 Technical.'' The active ingredient is 80% w/w (minimum of x 10 9 colony forming units/grams (unit of measure for bacteria (cfu/g)) in each of the propos ed technical products. Two end

- use products containing equal parts of Aureobasidium pullulans strains DSM 14940 and DSM 14941 are currently registered by EPA. Blossom Protect is applied to pome fruit and walnuts only during the blossoming period to protec t plants against bacterial fire blight and walnut blight, respectively. Botector is currently applied pre

- harvest to grapes, pome fruit, stone fruit, and strawberries. Bio

- ferm proposes to amend the Botector label to permit post

- harvest uses, presently onl y to citrus, to protect these crops against fruit rot diseases caused by blue and green mold caused by Penicillium spp. and sour rot caused by

Geotrichum spp. Post

- harvest application rates are projected to be up to 1 pound of Botector per 60 gallons

of wa ter (as a 0.2% spr ay or dip).

B. Microbial Pesticide Toxicology Data Requirements The Agency has determined that all mammalian toxicology data requirements submitted to support the petition to exempt residues of Aureobasidium pullulans strains DSM 14940 and DSM 14941 from the requirement of a tolerance have been fulfilled (Ref. 13 ) and that the submitted data ( MRID 49717901) are acceptable to an expansion of the tolerance exemption to include post

- harvest use sites (Ref. 14)

.

The product analysis data demonstrated that Aureobasidium pullulans strain DSM 14941 is closely related

to strain DSM 14940. Because the strains are closely related, the Agency has determined that the findings of the submitted acute toxicity/ pathogenicity studies conducted only w ith strain DSM 14941 supported

both strains, and those studies show no evidence of toxicity, or pathogenicity at the doses tested. In addition, both strains were tested in an acute subcutaneous injection toxicity/ pathogenicity study in rats.

The results of this study indicated that both strains were not toxic, infective, and/or pathogenic to the test

animals. These findings were supported by the results of a study of the influence of temperature on the growth of the two Aureobasidium pullulans strains, wh ich showed that growth of both strains does not
occur at or above 35 °C. Since human body temperature is 37 °C, and based on the results from these

studies as discussed in this unit the Agency concluded that neither strain would be toxic, infective and/or pathogenic in humans.

1. Acute Oral Toxicity/Pathogenicity (Office of Chemical Safety and Pollution Prevention (OCSPP)

Guideline 885.3050 ; Master Record Identification Number (MRID) No. 47899302. Twenty

- four rats were administered a single dose of Aureoba sidium pullulans strain DSM 14941. Three animals of each sex

were sacrificed on days 3, 7, and 14; the remaining animals were sacrificed at test end on day 21. Body

tissues were examined for Aureobasidium pullulans. All samples of feces, blood, brain, lung, liver, kidney, spleen, stomach, and intestine were negative. The lymph nodes of one animal sacrificed on day 7 tested positive for the presence of Aureobasidium pullulans DSM 14941. These findings show a pattern of

clearance with no Aureobasidium pul lulans DSM 14941 detected by day 14. The results of this acceptable3 study d emonstrated that Aureobasidium pullulan s DSM 14941 was not toxic, infective, and/or pathogenic in rats, when dosed at 4 × 10 8 cfu/animal.

2. Acute Pulmonary Toxicity/Pathogenicity (OCSPP Guideline 885.3150; MRID No. 47899303). Male and female animals were exposed intratracheally with Aureobasidium pullulans strain DSM 14941

Technical (4 × 10 8 cfu/g). Interim sacrifices were made 3 hours post

- dose and on study days 3, 7, and 14;

the remaining animals were sacrificed at study end on day 21. There was no mortality, and, except on the day of dosing when the entire test material group showed reduced motor activity and dyspnea, all

animals appeared normal throughout the study. Tissue sampl es were evaluated for Aureobasidium pullulans

after sacrifice. The following tissues were negative for Aureobasidium pullulans at all time points: Feces, brain, kidney, and intestine. Blood samples were negative except for one male on day 0; lung samples w ere negative except for two males and two females on day 0; liver samples were negative except for three males on day 0; spleen samples were negative except for two males on day 0; lymph node samples were negative except for one animal on day 7, and stomac h samples were negative except for two males on day 0. These findings show a pattern of clearance with no Aureobasidium pullulans DSM 14941 detected by day 14. The results of this acceptable study demonstrated that Aureobasidium pullulans DSM 14941 was

not toxic, infective, and/or pathogenic in rat, when dosed at 0.8 × 10 8 cfu/animal.

3. Acute Injection Toxicity/Pathogenicity (OCSPP Guideline 885.3200; MRID No. 47871807 and 47871808). In an acute subcutaneous toxicity/pathogenicity study (MRID 47871807), male and female rats

were injected with Aureobasidium pullulans strain DSM 14940 (2.36 × 10 10 cfu/g) and DSM 14941 (1.5 ×

10 10 cfu/g). Interim sacrifices were made on days 3, 7, and 14; the remaining animals were sacrificed at test end on day 21. There wer e no deaths, and all animals appeared normal throughout the study except for edema or slight erythema at the injection site. Samples of the following tissues were negative for Aureobasidium pullulans at all time points: Feces, blood, brain, lung, liver, ki dney, spleen, stomach, and

intestine. Lymph node samples were negative except for one animal sacrificed on day 7. The study author suggested this was likely a post

- mortem transmission. A pattern of clearance was observed in this study,

with no Aureobasidium pullulans DSM 14941 or 14940 detected by day 14. The results of this acceptable study demonstrated that Aureobasidium pullulans strains DSMZ 14940 and DSMZ 14941 were not toxic, infective, and/or pathogenic in rats, when dosed at 1.95 × 10 7 o r 1.12 × 10 7 cfu/animal, respectively. In a

second acute subcutaneous toxicity/pathogenicity study (MRID 47871808), male and female rats were injected with Aureobasidium pullulans strain DSM 14941 (1.1 × 10 9 cfu/g). Interim sacrifices were made on days 1and 7; the remaining animals were sacrificed at test end on day 21. There were no deaths, and all

animals appeared normal throughout the study except for severe edema or slight erythema at the injection site. Samples of the following tissues were negative for Aureobasidium pullulans at all time points: Brain, lung, spleen, kidney, lymph nodes, blood and urine. The skin was positive for Aureobasidium pullulans in

three males and three females from the test material group on day 1 and in two females of the same group on day 7. The liver of one male from the test material group was positive on day 1. The cecum contents were positive in one male and one female from the test material group on day 1 and in two females from

the same group on day 7. These findings show a pattern of clearance with no Aureobasidium pullulans

DSM 14941 detected by day 21. The results of this acceptable study d emonstrated that Aureobasidium pullulans DSM 14941 was not toxic, infective, and/or pathogenic in rats, when dosed at 1.6 × 10 7

cfu/ animal.

4. Acute Dermal Toxicity (OCSPP Guideline 870.1200; MRID 47869615).

In an acute dermal toxicity study, the shaved skin of 10 rats was dosed with 2,000 milligram/kilogram (mg/kg) Blossom Protect (7 × 10 9 cfu/g each of strains DSM 14940 and DSM 14941) for

24 hours. One male exhibited chromodacryorrhea from day 7 to day 14 and one female exhibited chromodacryorrhea from day 1 to day 2 of the study, but this was not considered to be toxicologically4 significant because this is a normal but rare resp onse and it did not result in mortality. All animals appeared healthy at necropsy. The lethal dose (LD 50 ) was >2,000 mg/kg. This study was rated acceptable, and the end use product (EP) is classified as toxicity category IV.

5. Primary Dermal Irritation (OCSPP Guideline 870.2500; MRID 47869619).

In a dermal irritation study, the shaved skin of 3 rabbits was dosed with 0.5 g Blossom Protect (7 × 10 9
cfu/g Aureobasidium pullulans strain DSM 14940 and 7 × 10 9 cfu/g Aureobasidium pullulans strain DSM 14941) moistened with 1.0 milliliter (mL) deionized water for 4 hours. All animals appeared normal throughout the study; thus, Blossom Protect was considered to be non

- irritating. This study was rated acceptable, and the EP is classified as toxicity category IV.

6. Acute Oral Toxicity (OCSPP Guideline 870.1100; MRID No. 47869614. ) In an acute oral toxicity study, six animals received a single 2,000 mg/kg body weight (bw) dose of Blossom Protect 22% (2 × 10 10
cfu/g) Aureobasidium pullulans strain DSM 14940, 22% (2 × 10 10 cfu/g) Aureobasidium pullulans strain

DSM 14941, 25% sucrose, 6% water. There was no mortality, and all animals appeared normal throughout the study. The LD 50 was >2,000 mg/kg. This study was rated acceptable, and the EP is classified as toxicity

c ategory III.

7 . Acute Inhalation Toxicity (OCSPP Guideline 870.1300; MRID 47869617).

In an acute inhalation toxicity study, 10 animals were exposed nose

- only to a 10% suspension of Blossom Protect (7 × 10 9 cfu/g A. pullulans strain DSM 14940 and 7 × 10 9 cfu/g A. pullulans strain DSM 14941) at 5.17 milligrams per liter (mg/L). The Mass Medium Aerodynamic Diameter (MMAD) was 4.2 mm. There

were no deaths and all animals appeared healthy throughout the study. Necropsy was unremarkable.

The lethal concentration (LC 50 ) was >5.17 mg/L. This study was rated acceptable, and the EP is classified

as toxicity category IV.

8. Acute Eye Irritation (OCSPP Guideline 870.2400; MRID 47869618)

. In an eye irritation study, three rabbits were dosed with 0.1 mL (6 0

– 62 grams (g) of Blossom Protect (7 ×

10 9 cfu/g A.pullulans strain DSM 14940 and 7 × 10 9 cfu/g A. pullulans strain DSM 14941). One animal had

a score of 1 for conjunctival redness 1 hour after application. There were no other clinical signs, and all animals appeared normal at 24 hours. Blossom protect was considered to be virtually non

- irritating. This study was rated acceptable, and the EP is classified as toxicity category IV.

9. In vivo Micronucleus Assay (MRID 47899304). Twenty mice (two groups o f five male and two groups

of five female mice) received single 2,000 mg/kg Aureobasidium pullulans strain DSM 14941 dissolved in water by oral gavage. There were no clinical signs observed in any of the test animals, which were

sacrificed 24 or 48 hours a fter receiving the test material. The femoral bone marrow was immediately harvested, and the ratio of polychromatic erythrocytes to total erythrocytes (mature and immature) was determined, and 2,000 immature erythrocytes/animal were scored for the presence of micronucleated immature erythrocytes, a sign of potential toxicity or damage to genetic material in the cells. Aureobasidium pullulans strain DSM 14941 did not produce a statistically significant increase in

micronucleated immature erythrocytes compared to the untreated control animals. The response of the positive control animals (treated with a known toxic substance, cyclophosphamide, by intraperitoneal injection, at 10 mg/kg) was appropriate for comparison and did produce a statistically signi ficant increase

in micronucleated immature erythrocytes compared to the untreated control animals. This study was rated acceptable.

10. Influence of Temperature on Reproduction (MRID 47871833). Aureobasidium pullulans strain CBS 626.85 was isolated from the peritoneal dialysis fluid of a human in5 Australia. The effects of temperature on the reproduction or growth of Aureobasidium pullulans strains

DSM 14940 and, DSM 14941, in liquid culture or on agar plates were examined and compared against this positiv e control, Aureobasidium pullulans strain CBS 626.85, to observe the ability of these strains to reproduce at human body temperature of 37 °C. All three strains grew well at 30 °C. At 33 °C, the number of replications (per 48 hours) of the Aureobasidium pullulans strains DSM 14940 and, DSM 14941

was less than one, while the number of duplications for strain CBS 626.85 was approximately five. Neither

strain DSM 14940 or strain DSM 14941 was able to grow at 35 °C or 37 °C, while strain CBS 625 .85 replicated (approximately) twice at 35 °C and once at 37 °C. Based on the lack of growth of the DSM

strains at 35 °C and above, and given human body temperature is 37 °C, Aureobasidium pullulan strains

DSM 14940 and DSM 14941 are expected to be nonpath ogenic in humans. This study was rated acceptable.

11. Hypersensitivity Incidents (OCSPP Guideline 885.3400; MRID No. 47945023). No hypersensitivity incidents, including immediate

- type or delayed

- type reactions of humans and domestic animals during research, development, or testing of Aureobasidium pullulans strains DSM 14940 and DSM 14941 were reported by the applicant. Any future hypersensitivity incidents must be reported per OCSPP Guideline

885.3400.

III. 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 wat er and exposure through pesticide use in gardens, lawns, or buildings (residential and other indoor uses).

Food Exposure : Should this microbial pesticide be present on food, the acute toxicity, infectivity, and pathogenicity data, as well as the data demonstrating the lack of growth at human body temperature

submitted for Aureobasidium pullulans strains DSM 14940 and DSM 1494 1 demonstrated that no toxicity, infectivity, and/or pathogenicity is likely to occur with any exposure level resulting from application of these two pesticide active ingredients in accordance with good agricultural practices (see Unit II above).

Aureo basidium pullulans strains DSM 14940 and DSM 14941 sprayed pre

- harvest still have residues detected post

- harvest, and no pathogenic effects have been reported. Nor have pathogenic effects been reported when Aureobasidium pullulans strains DSM 14940 and DSM 14941 are applied on stored fruits.

Drinking Water Exposure : Naturally occurring Aureobasidium pullulans is ubiquitous and has been isolated from all types of wate r (Ref. 1 5 ). Exposure of humans to residues of pesticides containing Aureobasidium pullulan s strains DSM 14940 and DSM 14941 in consumed drinking water is possible but potential exposure through drinking water is reduced, given the proposed use patterns, use sites, and application methods for Aureobasidium pullulans strains DSM 14940 and DSM 14941, which do not include direct application to aquatic environments. In the event that Aureobasidium pullulans strains DSM 14940 and DSM 14941 are transferred to surface water or ground water intended for human consumption, the fungi would not surv ive the high temperatures, chlorination, pH adjustments, and/or filtration water is subjected to in a drinking water treatment facility. Even if oral exposure should occur through consumed drinking water, there is a reasonable certainty that no harm will r esult from exposure to such residues, based upon the lack of toxicity, infectivity, and/or pathogenicity, as well as the inability of these fungal strains to grow at human body temperature, demonstrated in the previously described toxicological studie s (se e Unit II)6 Other Non

- occupational Exposure : The use sites for these products include residential garden sites and agricultural sites. Aureobasidium pullulans is naturally present in many habitats, and based on the data and

other information submitted to satisfy data requirements for registration of the MPs and EPs containing the active ingredients Aureobasidium pullulans strains DSM 14940 and DSM 14941, no toxicity, infectivity, pathogenicity or other adverse effects from non

- occupational exposure are ex pected , and none have been reported to EPA. (see Unit II)

IV. 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.”

Aureobasidium pullulans strains DSM 14940 and DSM 14941 are not toxic vi a the oral, dermal, or inhalation routes of exposure. Thus, f or the purposes of this tolerance action, the EPA has concluded that

A ureobasidium pullulans strains DSM 14940 and DSM 14941 do not have a common mechanism of toxicity with other substances. Foll owing from this, therefore, the EPA concludes that there are no

cumu lative effects associated with A ureobasidium pullulans strains DSM 14940 and DSM 14941 that need

to be considered.

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/cumulati ve

.

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

FFDCA section 408(b)(2)(C) provides that EPA shall assess the available information about consumption patterns among infants and children, special susceptibility of infants and children to pesticide chemical residues, and the cumulative effects on infant s and children of the residues and other substances with a common mechanism of toxicity. In addition, FFDCA section 408(b)(2)(C) provides that EPA shall apply an additional tenfold (10X) margin of safety for infants and children in the case of threshold ef fects to account for prenatal and postnatal toxicity and the completeness of the database on toxicity and exposure unless EPA determines that a different margin of safety will be safe for infants and children. This additional margin of safety is commonly r eferred to as the FQPA Safety Factor. In applying this provision, EPA either retains the default value of 10X or uses a different additional safety factor when reliable data available to EPA support the choice of a different factor.

Based on the acute toxicity and pathogenicity data summarized in Unit II.B., EPA concludes that there is a reasonable certainty that no harm will result to the U.S. population, including infants and children, from aggregate exposure to the residues of Aureobasidium pullulans strains DSM 14940 and DSM 14941. This includes all anticipated dietary exposures and all other exposures for which there is reliable information.

EPA has arrived at this conclusion because the data and information available on Aureobasidium pullulans

stra ins DSM 14940 and DSM 14941 do not demonstrate toxic, pathogenic, and/or infective potential to mammals. Thus, there are no threshold effects of concern and, as a result, the Agency has concluded that an additional margin of safety for infants and children is unnecessary in this instance. Further, the need to consider consumption patterns, special susceptibility, and cumulative effects does not arise when dealing with pesticides with no demonstrated significant adverse effects.7 VI. Conclusions

The EPA co ncludes that there is a reasonable certainty that no harm will result to the U.S. population, including infants and children, from aggregate exposure to residues of Aureobasidium pullulans strains

DSM 14940 and DSM 14941 . Therefore, an exemption from the r equirement of a tolerance is established

for residues of A ureobasidium pullulans strains DSM 14940 and DSM 14941 in or on all food commodities when used in accordance with label directions and good agricultural practices.

VII . References

1. Chi, Z., F. Wang, Z. Chi, L. Yue, G. Liu, T. Zhang. 2009. Bioproducts from A ureobasidium pullulans, a biotechnologically important yeas t. Appl. Microbiol. Biotechnol. 82: 793

- 804.

2. Cooke, W.B. 1959. An ecological life history of Aureobasidium pullulan s (De Bary) Arnaud. Mycopathologia, 12: 1

- 45.

3. Slepecky, R.A. and W.T. Starmer. 2009. Phenotypic plasticity in fungi: a review with observations on Aureobasidium pullulans. Mycologia 101: 823

- 832.

4. Fleet, G.H. 2002. The yeast ecology of wine grapes. Pp. 1

- 17 in Biodiversity and Biotechnol. Of Wine Yeasts (Ciani, M., ed. ). Research Signpost, Kerala, India.

5. Fleet, G.H. 2003. Yeast interactions and wine flavor. Int. J. Food Microbiol., 86: 11

- 22.

6. Granado, J., B. Thurig, E. Kieffer, L. Petrini, A. Fliessbach, L. Tamm, F.P. Weibel, G.S. Wyss. 2008. Culturable fungi of stored `Golden Delicious' apple fruits: a one

- season comparison study of organic and integrated production systems in Switzerland. Microb. Ecol., 56: 720

- 732.

7. Gao, X.

- X., H. Zhou, D.

- Y. Xu, C.

- H. Yu, Y.

- Q. Chen, L.

- H. Qu. 2005. High diversity of endophytic fungi from the pharmaceutical plant, Heterosmilax japonica Kunth revealed by cultivation

- independent approach. FEMS Microbiol. Letters, 249: 255

- 266.

8. Osono, T. 2008. Endophytic and epiphytic phyllosphere fungi of Camellia japonica: seasonal and leaf

age

- dependent variations. Mycologia, 100: 387

- 391.

9. Slavikova, E., R. Vadkertiova, and D. Vranova. 2007. Yeasts colonizing the l eaf surfaces. J. Basic

Microbiol. 47: 344

- 350.

10. Suryanarayanan, T.S., S.K. Wittlinger, and S.H. Faeth. 2005. Endophytic fungi associated with cacti in Arizona. Mycol. Res. 109: 635

- 639.

11. Webb, T.A. and J.O. Mundt. 1978. Molds on vegetables at the tim e of harvest. Appl. Environ. Microbiol., 35: 655

- 658.

12. Kockova

- Kratochvilova, A., M. Cernakova, and E. Slavikova. 1980. Morphological changes during the life cycle of Aureobasidium pullulans (de Bary) Arnaud. Folia Microbiologica, 25.

13. U.S . EPA

. January 2012 Biopesticides Registration Action Document of Aureobasidium pullulans

strains DSM 14940 and 14941.8 1 4 . U.S. EPA. October 2015

. Review of the Registrant’s response to a 75

- day deficiency letter concerning a petition by the registrant to add Po st Harvest use to its registered product Botector containing Aureobasidium pullulans strains DSM 14940 & DSM 14941. Memorandum from I.S. Barsoum, Ph.D., and J. L. Kough, Ph.D. to S. Cerrelli, dated October 6, 2015

1 5 . Slavikova, E. and R. Vadkertiova. 1997 . Seasonal occurrence of yeasts and yeast like organisms in the

river Danube. Antonie van Leeuwenhoek 72: 77

- 80, 1997.