### UN IT E D STATES ENVI RO NMENTA L PROTECTION AGENCY WASHING TON, D.C. 20460

M EM ORANDUM

SUBJECT:

F ROM :

THROUGH :

TO : 

### C~T 

## 0 

## 6 7015 OFFICE OF PREVENTION , PE STICIDES AND TOXIC SUBSTANCES

Rev iew of the Registrant 's response to a 75- day deficie ncy l ette r concerning a peti t ion by the regist rant to add Post Harvest use to its regis tered product Botector co ntainin g 

### Aureobas i d ium pullulans strain s DSM 14940 & 

### D SM 14941.



# 11~ **J)~**

**!o Ju;tr**  Ibrahim S. Barsoum, Ph.D. , M icrobiologist .J · 

### Microb ial Pesticides Branch , Biopesticides and P o lluti on Prevention Division John L. 

### Kough , Ph.D., Senior Scie n ti st M icrobial Pesticides Branch , Biopesticides and Pollution Prevention Suzrume Cerrelli, Regulatory Action Leader Microbial Pesticides Branch , Biopesticides and Po lluti on Prevention Division (75 11 C)

AC TION REQUES TED: T o r ev iew the Reg istrant's response to th e 75-day deficiency letter (dated Jul y 15 , 20 1 5) concerni n g a pet ition by the registrant to add Post H a rvest use to its registered product Botector (EPA Reg
. no. 86 1 74-3) contain in g 

### A ureobasidium pulfulans strai n s DSM 14940 

### & D SM 14941

CONCLUS I ON: ACCEPTA BLE

### DATA REVI EW RECORD Active Ingredient s : Products Name : Company Name: lD No: C h e mical Number: Submission N umb e r : DP Barcode: MRIDNo: 

### BACKGROUND: Aureo basidium pullulans s trains DSM 14940 & D S M 14941. Botector BIO-FERM GMBH 86174 -3 0360 10 , 046010 97402 1 429403 497179 -01

The registrant ha s subm itted a petition for Post- H arvest u se to amend th e regis t e r product Botecto r ( EP A Re g. no. 86174

- 3). The Agency has id e ntified concerns about potential effects of post-harvest appli cat io n s on human health. T he se concerns are based o n reports in the publi s h ed literature of infections ca u se d by 

### Aureobasidium pullu/ans particularly in immune-compromi se d patients and was unabl e to amend the tolerance ex emption for the produ c t lab e l as requested. To address these concern s the Agency has re que s ted that th e registrant sub mit s additional scientific rationale that s uppoti s th e s afety of post-harv es t application to indi v idu a l s that may consume food products after post-harvest treatment. 

### Registrant's response to refute harmful health effect of po st- h arvest us e of Botector: 1. 

### A. pul/ulans i s a cosmopo litan yea s t
- like fungus a nd ubiquit ous ly d i s tributed in different e n vi ro nments and 

### it la cks of a n y kind of in vasiveness int o the human organism. The s tra in s DSM 14940 and DSM 14941 are not able to g row at 37 ° C and did not cause any sy mptoms in toxicity or path oge nicity studi es in r a t s a nd rabbits. 2. The s p ec ie s 

### A. p ullulan s i s furth ennore class ifi ed in BSL-1 ( Bi o- s afe ty leve l I) ( d e Hoag , 1 996). In BSL-1 fungi are c lassi fi ed , whic h a re n ot h a rmful. eve n ift here a r e s in g le report s on the in vo l veme nt in h uman diseases
. 3. 

### A. pullulan s s trai n s from case studies on human pathogenicity a rc often n ot we ll classified on s pec ies leve l , mu st be abl e to g row at 37 ° C. w hi ch i s a pr erequ i s ite to colonize the hum an o rgan i sm , or are graded as co ntamin an t a nd n o t as pathogen (Ma t s um o to 

### e t a!. 1987). 4. In th e re la ti o n to fr e quency , in w hi c h hum a n s ge t in contac t to spo res of the spec ies A
. 

### pullu/ans. th e r eports on pathogen i c ity a re rare. The likelih ood of a contact with th e s por es of 

### A. pu/lu /

ans in daily lif e i s ve ry hi gh as the s p ec ies i s ubiquitous. 5. Due to th e fac t th a t 

### A
. pulfulans i s frequen tl y fo und on vegetab les ( Webb a nd Mundt. 1 978) grape s ( Fleet , 2003 ) a nd app le s (G r anado 

### e ta/. , 2008 ) under nat ura l condition s,

2the post-harve s t treatment with 

### A. pullulans strains DSM 14940 and DSM 14941 g i ve no add i tional risk to the consume r . Reviewers ' Comments : Th e reg istrant has p resen t e d th e fo ll ow in g scie nt i fi c ev ide n ce: I. The two strains of

### Aureobasidium pullulans DSM 14940 & 1494 1 do not grow at 37° C whi le other strains isolated from human infections do grow at this temperature. 2. 

### A. pullulans DSM 14940 

### & 1 4941 sp rayed pre harvest have still residues detected postharvest , and no pathogenic effect has been reported. 3. No pathogen i c effect has been reported when 

### A. pullulans D S M 14940 & 14941 are app li ed o n stored f rui ts. S ince Botector h as s hown to be no n-toxic, n on-pa th oge n ic, a nd non -i nfec tive in expe ri menta l toxicity s tu dies, it can be deduced th at Botecto r can be used post- h arvest, as long as i t is u sed at the allowable rate of application to reduce excess exposure to the microo rganism.

**NC ~O**  **N:** 

### ACCE PTABL E
REFERENCES : I. De Hoog. G.S
.. Yurlova, N
. A., 1994
. Conidioge nesis , nutritional physiology and taxonom y of Au reobas idium and Horm o nema. Anton ie Van Leeuwenhoek 65, 41-54. 2. Matsumoto. 

### T.. Padhye , A.A., Ajello, 

### L.. 1 987. Medical significance ofthe soca ll ed black yeasts. Eur. J
. Ep idem iology
. 3, 87-95. 3. Webb , T.A
. , Mundt, J
. O., 1 978
. M o lds on vegetab les at the t ime of ha rvest. Appl. Environ M icrobia l 35, 655-658. 4. Fleet, G.H., 2003. Yeast interaction s and w in e tlavor.lnt. Food M icrobi ol. 86, 11- 22. 

### s. Granado.J
.. Thorig, B
. . Kieffer , E., Petr i ni , L. , Tamm, L.. W e ib e l , F.P., Wyss , G.S
.. 2008.Cu l turab le F u ngi of Sto red Golden De l iciou s App le F r u its: A On e -S easo n Co m pa ri son Study ofOrgan ic and Integ rated P roduc ti on Systems in Sw it ze rl a n d M i crob ia l. Eco l. 56, 720-732
.



### 3