D ATA EVALUATION RECORD PAECILOMYCES FUMOSOROSEUS APOPKA STRAIN 97

( PFR- 97 20% WDG) STUDY TYPE: Request for Exemption From the Requirement of a Tolerance No MRID Number
Prepared for Biopesticides and Pollution Prevention Division Office of Pesticide Programs U.S. Environmental Protection Agency

One Potomac Yard 2777 South Crystal Drive Arlington, VA 22202 Prepared b y Toxicology

and Hazard Assessment Group Environmental Sciences Division Oak Ridge National Laboratory Oak Ridge, TN 37830 Task Order No. 10

- 01 3

Primary Reviewer: Eric B. Lewis, M.S. Signature: Date: Secondary Reviewers: Sylvia Milanez, Ph.D., D.A.B.T. Signature: Date: Robert H. Ross, M.S., Group Leader Signature: Date: Quality Assurance: Lee Ann Wi l son, M.A

. Signature: Date:

Disclaimer This review may

have been altered subsequent to the contractor ’ s signatures above. Oak Ridge National Laboratory managed and operated by UT

- Battelle, LLC., for the U.S. Department of Energy und er Contract No. DE

- AC05

- 00OR22725.1 DATA EVALUATION RECORD EPA Secondary Reviewer: Ib rahim S. Barsoum, Ph.D.

STUDY TYPE: Request for an Exemption from the Requirement of a Tolerance MRID NO: None DECISION NO: 42 5259 DP BARCODE: DP 3 7 446 3 TEST MATERIAL: PFR

- 27 20% WDG (a.i., 20.0% Pa ecilomyces fumosoro s eus

Apopka S train 97 ) PROJECT STUDY NO: Not provided

SPONSOR: Certis U.S.A., L .L .C., 9145 Guilford Road, Suite 175, Columbia,

MD 21046 TESTING FACILITY: Not applicable TITLE OF REPORT: Petition Proposing an Exemption From the Requirement of a Tolerance for the Use of the Microbial Pest Control Agent Paecilomyces fumosoro s eus Apopka Strain 97 AUTHOR: Wagner, J. STUDY COMPLETED: December 1 4 , 2009 CONFIDENTIALITY

CLAIMS : None. GOOD LABORATORY

PRACTICE: Not applicable CONCLUSION : The petition supports the requested exemption from the

requirement of a tolerance Paecilomyces fumosoroseus Apopka Strain 97 in/on all agricultural commodities

. Summary of Petition Proposed Use PFR

- 27 20% WDG is an end use product currently registered (EPA Reg. No. 70051

- 19) for control of insects and mites on ornamental plants grown in greenhouses and nurseries. The registrant proposes to amend the product label to allow use on vegetables, fruit s, ornamental plants, and other crops grown either outdoors, in greenhouses or under other cover, or in nurseries. As a result, the registrant has submitted a petition for an exemption from the requirement of a tolerance for residues of the active ingredient, Paecilomyces fumosoro s eus Apopka Strain 97 , in/on all agricultural commodities

. Product Identity/Chemistry/Magnitude of the Residue Paecilomyces fumosoroseus Apopka Strain 97 is a naturall y- occurring entomopathogenic fungus that can infect and control several insect pests, including whiteflies, thrips, aphids, and spider mites. Under the proper environmental conditions, spores of the fungus penetrate the cuticle of the insect and grow inside it, causing its death. Paecilomyces fumosoroseus Apopka Strain 97 was originally

isolated in 1986 from a meal ybug in a greenhouse in Apopka, Florida. The pure culture was identified in 1988, and deposited at the American Ty pe Culture Collection (ATCC #20874).2

Since Paecilomyces fumosoroseus Apopka Strain 97 occurs naturally in soils worldwide, humans, other animals, and plants are constantl y exposed to this fungus. Its use as proposed is not expected to result in residues that are of toxicological concern. Paecilomyces fumosorose us Apopka Strain 97 is affected by sunlight, temperature, humidity , substrate, and chemicals, which reduces the potential for residues to occur. Normal washing after harvest and before sale would further reduce or remove any residues. There is a low probab ility of its germination on harvested crops in the absence of an insect host, which further reduces the chance of residues that are of toxicological concern. Furthermore, an y potentially

- occurring residue on crops would not harm humans, since the strain shows no toxicity , infectivity , or pathogenicity in the appropriate tests. The optimal temperature range for growth, germination, and sporulation of the strain is 20 to 30°C, while the normal body temperatures of humans, other mammals, and avian species ar e significantly higher. Paecilomyces fumosoroseus Apopka Strain 97 is produced using a liquid fermentation. Secondary

metabolites such as beauverolides and beauvericine have been detected in still culture, but not in liquid fermentation.
Mammalian Tox ic ity Profile Acute oral toxicity

/pathogenicity

– rat : an oral dose of 1.7 x 10 6 cfu/animal in a conidia spore suspension did not produce mortality or abnormal clinical effects. No signs of fungal contamination were reported for the brain, mesenteric l ymph nodes, blood, kidney , spleen, liver, lung or cecum , and no infectivity or pathogenicity w as recorded

. Acute intraperitoneal toxicity /pathogenicity
– rat : Single intraperitoneal doses of suspensions containing 1.6 x 1 0 7 conidia spores per animal had no toxic or pathogenic effects and the spores were cleared from the body within two day s. Acute pulmonary

toxicity /pathogenicity

– rat : a single intratracheal dose (10 6 conidia spores/animal) resulted in n o deaths and there were no signs of toxicity in any animal. No signs of infection were seen and no colonization of the lungs was observed. Total clearance of the fungus was attained b y day eight after treatment. T he product was classified as T oxicity C ategory IV. Acute dermal toxicity

/pathogenicity

– rat : 2 grams of test substance applied to the skin of rabbits produced n o deaths and there was no evidence of sy stemic toxicity

. T he product was classified as T oxicity C ategory

III. Primary eye irritation

– rabbit : 0.1 mL of diluted test substance containing ≥10 7 cfu was instilled in the eye , which was examined at 1, 24, 48 and 72 hours , and at 4 and 7 day s after treatment. The test substance produced slight irritation which was reversible b y day 4 after treatment. T he product was classified as T oxicity C ategory IV. Dermal irritation

– rabbit : in a four

- hour exposure, the test substance (2 g/animial) was found to be a slight dermal irritant . The product was classified the product as T oxicity C ategory IV. Dermal sensitization

– guinea pig : The test substance (3.0 x 10 7

– 5.3 x 10 9 cfu) produced no3

irritation or sensitization reaction in treated animals. The product was not a dermal sensitizer. Mutagenicity

Test on Salmonella t

yphimurium (Ames Assay) : Sonicated blastospores and mycelium of Paecilomyces fumosoroseus Apopka strain 97 (100

– 5000 μg/plate) yi elded negative results in a reverse mutation assay in both the presence and absence of microsomal enzy mes (S9). Aggregate Exposure Food It is expected that, when used as proposed, Paecilomyces fumosoroseus Apopka strain 97 w ill not result in residues that are of toxicological concern. It s growth and survival is affected b y sunlight, temperature, humidity , substrate, and chemicals , especial ly fungicides

. A fter harvest , any remaining spores on crops will be exposed to unfavorable conditions (e.g. dry ness), and are not likely to germinate and grow on the harvested crop. Any potential residu es on these crops will not harm humans because the fun gal strain shows no toxicity , infectivity , or pathogenicity in appropriate tests. Further , the optimal temperature range for growth, germination and sporulation is between 20 and 30 ° C while the normal body temperatures of humans, other mammalian species and avian species are significantl y higher and unsuitable for growth and reproduction of Paecilomyces fumosoroseus Apopka strain 97. While the proposed use pattern may result in dietary exposure with possible residues in or on certain agricultural commodities, negligible to no risk is expected for the general population, including infants and children, or animals because Paecilomyces fumosoroseus Apopka strain 97 demonstrated no pathoge nicity or toxicity

at the maximum doses tested , generall y limit doses

. Drinking Water Paecilomyces fumosoroseus Apopka strain 97 is not known as an aquatic microorganism, and is not expected to proliferate in aquatic habitats. There are no aquatic use sites permitted for this pesticide, so exposure to drinking water is not expected. P ercolation through soil and muni cipal treatment of drinking water would reduce the possibility of exposure to Paecilomyces fumosoroseus Apopka strain 97 via drinking water. The potential of significant transfer to drinking water is minimal to nonexistent. Even if low levels of the microb e were present in drinking water, no risk to the general public would be expected because Paecilomyces fumosoroseus Apopka strain 97 demonstrated no pathogenicity or toxicity

at the maximum dose tested. Non

- Dietary

Exposure Since Paecilomyces fumosoroseus Apopka strain 97 occurs naturally , there may be non

- dietary exposure from background levels. Humans may be exposed dermally

or orally via soil on their hands or clothing, or by

handling pets that have played in soil. However, no toxicological endpoints were identified for Paecilomyces fumosoroseus Apopka strain 97 , and there is no4

evidence of adverse effects from oral, dermal, or pulmonary exposure. It is not expected that the pesticidal use of Paecilomyces fumosoroseus Apopka strain 97 will significantly increase the non - dietary

and non

- occupational exposure to the fungus. Based on the proposed use patterns, the potential for non

- dietary , non - occupational exposures to residues b y the general population, including infants and c hildren, is low. Cumulative Exposure/Determination of Safety for U.S. Population, Infants, and Children There is reasonable certainty that no harm will result to the U.S. population, including infants and children, from aggregate exposures to residues of Paecilomyces fumosoroseus Apopka strain 97 as a result of its proposed uses. This includes all anticipated dietary exposures and all other exposures for which there is reliable information. There appears to be no potential for harm from this fungus in its use as a microbial pesticide in agricultural commodities. Furthermore, the organism is non

- toxic and non

- pathogenic to animals and humans , based on the results of the mammalian toxicity

tests. Moreover, potential non

- occupational inhalation or dermal expos ure is not expected to pose any adverse effects to exposed populations via aggregate and cumulative exposure. Effects on Immune and Endocrine Systems There is no information to indicate that Paecilomyces fumosoroseus Apopka strain 97 would have an effect i n humans similar to an effect produced by a naturall y- occurring estrogen or other endocrine effects. There is no known metabolite produced by this fungus that acts as an endocrine disruptor. The submitted toxicity /pathogenicity

studies in rodents indicate that no viable conidia or blastospores were found in organs or tissues of the test animals. It is concluded that there will be no incremental adverse effects to the endocrine s ys tem. Existing Tolerances None. International Tolerances The European Food Safe ty Authority Scientific Report (2007), 115, 1

- 161, determined that under Regulation (EC) No 396/2005 of the European Parliament and of the Council on Maximum Residue Levels for pesticides (28 October 2007) that no MRL s and no residue definitions have to be established for the use of Paecilomyces fumosoroseus Apopka strain 97 on agricultural crops. Reviewers ’ Comments T he reviewer s believe the registrant ’ s petition supports the requested exemption from the requirement of a tolerance provided that the registrant test for beauverolides in production batches.