EPA'sRecordsDispositionSchedulePEST361 ScientificDataReviewsHEDRecordsCenter

-FileR153710
-Page 1of4

UNITEDSTATESENVIRONMENTALPROTECTIONAGENCY WASHINGTON. D.C.20460

OFFICE OF

## ./ i

PESl"ICIOES AND TOXIC SUBSl"ANCES**:~8IVlORANDUN** SUBJECT: "New chemical screen"; Toxicology Branch screen for reg:hstration of the fungus Gliocladium virens for greenhouse ornamental and greenhouse**foo~rop-u8es~----** TO: L. Schnaubelt (PIVl-21) Registration Division



## - ,J Roy D, Sjoblad, Ph.D. 

# .If.

# /J,;1**J?/~.:d:.,.** Microbiologist, SMSS, Toxicology Branch**~ ~'ROM:**  THROUGH: Reto Engler, Chief, SMSS Ph.D.

MPCA: Gliocladium virens

# ~/ 

# -. 8/lb(si

,
Pesticide Chemical Code: .28900-8 Product names: WRC-GL-21, and WRC-AP-1 Caswell

### #: EPA 

### Reg.H: 11688-U and l1688-G Pesticide petition 

### #: 8F3659

BaCKground: W,R. Grace 

### &Co. wishes to register the fungus Gliocladium virens strain GL-21 (from the USDA culture collection), Application is made for registration of the product designated WRC-GL-21 for manufacturinguse, and application for registration of the product designated as WRC-AP-1 is for use on ornamentals and food crops in the greenhouse. The Registrant requests a waiver for the requirement for the following studies, and for the following reasons: Acute dermal toxicity (Tier I): because the proposed labeling requires hand protection, and product ingredients are not known to be dermal toxicants, and testing with laboratory animals shows that the active ingredient is not pathogenic.**Prima~** eye irritation/infectivity study (Tier I): because proposed labeling requires eye protection while handling, and the active ingredient is not pathogenic to laboratory animals.EPA'sRecordsDispositionSchedulePEST361 ScientificDataReviewsHEDRecordsCenter-FileR153710-Page 2of 4

-2-

Hypersensitivity study: because the active lngredient is not pathogenic to laboratory animals and 

### no hypersensitive incidents have been observed over a two-year period among researchers working with the active ingredient_ The Registrant submItted for the screen an acute oral, and an acute pulmonary, and an acute intravenous study to support registration of the manufacturing-use and formulated products_ On April 6, 1988 representatives of EPA met with represenatatives of 

### W. R. Grace 

### &Co. to discuss data reQuirements for registration of Gliocladium virens for use as a fungicide in the greenhouse, The formulated product is to be applied by blending with soil or soil-less growing medium, or by surface application to soil followed by blending in with the top one-inch of soil medium prior to planting. A sample of the "prill" (pelleted) formulation of the fungus was brought to the meeting by the Registrant, Each spherical pellet was approximately several millimeters in diameter. For the purposes of Registration of Gliocladium virens for the proposed greenhouse uses, the Toxicology Branch recommended the foIlowing: An acute oral infectivity/toxicity study (according to the most recently available SubdiviSion Mguideline revisIons) using the pelleted form of the fungus. An acute ulmonar infectivit /toxicit stud (also according to recent SubdiviSion Mguidelines with the spore form of the fungus, since the large diameter of the formulated product prohibited use of the formulated product via pulmonary exposure, and It appeared that pulmonary exposure to the spore form of the fungus would be the most likely. However, if pulmonary exposure to significant amounts of the vegetative form is likely, then this form of the fungus may also have to be tested. 'rhe objective of the study is to provide information on the toxicity and clearance from test animals of the spore form of the active ingredient. An acute intravenous infectivit /toxicit stud (also according to recent reVised guidelines with the vegetative mycelial form of the fungus, to provide data on the infectivity and pathogeniCity of the active ingredient,

It was indicated to the Registrant that immune response studies currently are no longer being reqUired, and that reporting of hypersensitivity incidents is sufficient to replace the formerly reQuired hypersensitivity study. In addition, the eye irritation study (infectivity portion of study no longer required) need 

### not be done provided workers' eyes are protected from exposure to aerosols of the product, Also, dermal irritation studies are 

### not included as reQuired in the revised SubdiVision Mguidelines, however, dermalEPA'sRecordsDispositionSchedulePEST361 ScientificDataReviewsHEDRecordsCenter-FileR153710-Page 3of 4 

### -3-



## .

# .

toxicity studies are required, unless appropriate justification for their waiver is provided. 10xico]ogy Branch conclusions from screen of**data~kage:** The Registrant has submitted an acute ora] infectivity/toxicity study with the pelleted form of the product, and an acute pulmonary infectivity/toxicity study with the fungal spores, and an acute intravenous infectivity/toxicity study with the mycelial form of the fungus_ A written report stated that no hypersensitivity reactions were observed in eight researchers working with the fungus for up to two years, The request for waiving the eye irritation study on the basis of wearing of protective eye coverings during periods of potential exposure is adequate for waiving the study for the intended registration uses. The request for waiving the dermal toxicity study on the basis that the product ingredients are not known to be toxic and on the basis that the active ingredient is not pathogenic for humans are not sufficient reasons to grant a waiver of this study. However, the requirement for wearing of gloves during handling of the material coupled with the large pellet size of the product, and with its intended use via soil incorporation are sufficient for not requiring this study for the intended greenhouse uses. Thus, the acute oral, acute pulmonary, and acute intravenous studies proVided are sufficient in number to represent Tier I data requirements. Of course, this screen does not address the question of whether the three submitted studies provide acceptable data, and, thus whether Tier II studies will be required. This will be done when the studies are officially reviewed by the Toxicology Branch. A descriptive taxonomic characterization of the active fungal ingredient as Gliocladium virens was provided; however, it was not clear to this reviewer which characteristics allow for separation of this fungus from Trichoderma virens and Trichoderma viride, two fungi for which "_._Gliocladium virens has often been misidentified." Each batch of the fungus is monitored for several recognized mammalian pathogenic bacteria, and also for gliotoxin (assay method limits of detection are >10 mg/l), which is indicated as a potential impurity of**"toxicologi~** Significance." Apreliminary study on the effect that temperature has on limiting growth of the fungus showed that the active ingredient can grow at 

### 35C· but not at 

### 37C· or at 

### 40C·- The request for an exemption from tolerance for Gliocladium virens can be addressed subsequent to review of the above studies. Recommendation: The studies/information submitted are sufficient for the Toxicology Branch to recommend that the products containing G. virens pass the screen. However, the Registrant should provide 

# a more detailed taxonomic characterization of the test fungus, and a more detailed description of the toxicological properties of gliotoxin and on methods to determine its presence in product batches; and, also should provide more detailed studies evaluating the potential for fungal growth at 

### 37C·- The latter would be helpful if.data from the submitted mammalian toxicology studles are equlvocal wlth respect to infectivity in test animals,EPA'sRecordsDispositionSchedulePEST361 ScientificDataReviewsHEDRecordsCenter

-FileR153710
-Page 4of4

# ~ 13544

Chemical:

HEDFileCode: MemoDate: FileID: Accession#:



# • R153710

GliocladiumvirensG-21
PCCode:

129000 41500BPPDTox/Chem 8/16/1988 00000000 000-00-9003

HEDRecordsReferenceCenter 111112007 

# •

•