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SUBJECT:

TO:

FROM:

THROUGH: 

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UNITEDSTII,TESENVIRONMENTALPROTECTIONAGENCY WASHINGTON, D.C. 2()460

OFFICEOF PREVENTION,PESTICIDESAND SA.B Review of Data Submitted by W_R_ Grace and**rnill\I~¥N<tfO** support the Outdoor Use Regis,tration and Exemption from Tolerance of Gliocladium virens GL-21 and the End-Use Product, WRC-AP-1, (Submission No's,: S468683, S468684; DP Barcode No's.: D204818,. 0204820; 10 No_: 011688-00003; Chemical 10 No.: 129000).

Carl Grable/Clarence Lewis (PM 21) Fungicide-Herbicide Branch Registration Division (H7505C) cindy Schaffer, Microbiologist Biological Pesticides section science Analysis Branch Health Effects Division (H7509C)
Roy Sjoblad, Ph,D., section Head Biological Pesticide section Science Analysis Branch Health Effects Division (H7509C)

DATA REVIEW RECORD Product Name: GliocladiuJn virens GL-21 10 No.'s: 011688-0003, 4F04368 Chemical Ko: 129000 MRID No's 431115-01 Primary Eye Irritation (152A-14) 431271-01 Acute Dermal Toxicity (152A-11)

ACTION REQUESTED: SAB has been askE,d to review primary eye irritation and acute dermal toxicity data; and an exemption from tolerance in support of the outdoor use registration of Gliocladium virens GL-·21. W.R. Grace has aIso submitted waiver requests for the remaining acute toxicity studies for our review.**CON~LUSJON:** The toxicology data base is sufficient to support outdoor use registration Gliocladium virens GL-21 and WRC-AP-21. The waiver requests for the acute battery of studies (acute oral, acute dermal, acute pulmonary, acute intravenous and primary eye studies) were accepted cased on the lack of toxicity of the end-use product WRC-AP-l, which contains Gliocladium virens GL-21
as the active ingredient. The data submitt'ed is sufficient to support an exemption from the requirement for a tolerance.

Recycled/Recyclable PrIntedwltlhSoylCanolaInkonpaperthai contaInsatleast50%recycledfiberEPA'sRecordsDispositionSchedulePEST361 ScientificDataReviewsHED RecordsCenter

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with respect to the request to remove the glove and eye protection requirement;s from t.he label; SAB does not object to the removal ot the protective glove statement based on the lack of dermal toxicity but does not support the removal of protective eyewear from the end-use product label_ The registrant should generate a rationale for lack of expected eye irritation or physical eye injury from the end-use product and submit this for SAB revie",_

SUMMARY OF' DATA SUBMITTED: Acute Dermal (l52A-111.: Although GJ.iocladium virens GL-21 was not toxic tc rabbits when a 19 (1 X 10' CFU) dose/animal was applied dermally; this is not sufficient to fulfill the 2 g/kg limit dose_ CLASSIFICATION: SUPPLEMENTARY

- BasE,d on the known lack of toxicity of the inert: ingredients, SAB would have predicted Tox Category IV by the dermal route. The results support this assumption_ Primary &ye (l52A-14) :Overall, GJ.ioc.IadJ:um virens GL-21 produced a slight (Jccular irritation (draize score 1.85 at 72 hours post dosing). Irritation was no longer present by day 7. CLASSIFICATION: UNACCEPTABLE

- Since the end-use product was not used to evaluate eye irritation, SAB finds this study unacceptable for the purpose of label amendments for the end-use product. The registrant may be able to generate a rationale for lack of**I~xpected** eye irritation or physical eye injury from the end-use product.EPA'sRecordsDispositionSchedulePEST361 ScientificDataReviewsHED RecordsCenter

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Reviewed by: Secondary Reviewer: Cindy Schaffer, Microbiologist, SAB/HED**~** John Kough, Ph.D., Biologist, SAB/HED**r\,,~** STUDY**"=T~Y=P=E~:-~A~c"ute** Dermal Toxicity-Rabbit (152A-11) MRID NO: 431271-01 TEST MATERIAL: GL-21 Alginate Prill (EP: WRC-AP-1) SYNONYMS: Gliocladium yiremo; PROJECT NO: G-7131.232 SPONSOR: W.R. Grace 

### &Co., Columbia, MD TESTING FACILITY: Microbiological Associates, Bethesda, MD

TI'rLE OF REPORT: Acute Dermal Toxicity Test of GL-21 Alginate

AUTHORS(S) : STUDY COMPLETED: CCNCLUSION:

CLASSIFIC I'.'I'ION:

I. STUDY DESIGN Prill in Albino Rabbits. Raymond M. David, Ph.D, D.A.B.T. 13 December 1988 Although Gl.iocladium virens GL-21 was not toxic to rabbits \vhen a 19 (1 x 

### la' CFU) dose/animal 'Nas applied dermally; this is not sufficient to fulfill the 2 g/kg limit dose. SUPPLEMENTARY Based on the known lack of toxicity of the inert ingredients, SAB would have predicted Tox category IV by the dermal route.

TesteMa<:;erid.l: The microbial pest control agent (MPCA) is GL-21 Alginate Prill, lot number 14315-84. The conceni:ration was determined to be 1 x lOX colony Forminq Units (CFU)/gm

.. The MPCA was administered undilui:ed. Test**An~}!la]J?':** Five male and five female New Zealand albino rabbits
were obtained from Hazleton Research Products, Denver, PA. The rabbits weighed between 1.9 kg and 2.3 kg at the beginninq of the study.**Metho,t~,:** Approximately 24 hours prior to testing, no less than 10% of the trunk fur was clipped. The MPCA
was administered over the prepared skin followed by gauze and adhesive tape. The entire midsection was then securely wrapped with cloth toweling and fastened with adhesivr2 tape. Approximately**;~4** hours following application, all wrappings were removed and the skin Wa:3 wiped clean using paper towels moistened wi"th saline. The animals were observed for signs of toxicity at least twice on day 1 and daily thereafter. Body weights were recorded on day I, day 8 and day 15. At the end of the study, all animals were sacrificed by lethal injection and necropsy was performed.EPA'sRecordsDispositionSchedulePEST361 ScientificDataReviewsHED RecordsCenter

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II. RESULTS
A, .!lQgy Weights: No abnormalities were noted in body weight gain, B. Cl.inical Observations: Clinical signs were not noted during the study. C. !':!gcropsy observations: No abnormalities 'iJere observed in any rabbit upon necropsy.

III. SAB DISCUSSION: Although GL--21 Alginat.e Prill was not considered toxic at a single 1 g (1 x 10' CFU)/animal dose; this is not sufficient to fulfull the 2g/kg limit dose.EPA'sRecordsDispositionSchedulePEST361 ScientificDataReviewsHED RecordsCenter

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Heviewed by: Secondary Reviewer:

STUDY TYPE: MRID NO: TEST MATERIAL: PIWJECT NO: SPONSOR: TESTING FACILITY:

TITLE OF REPORT:

AUTHORS(S) : STUDY COMPLETED: CONC[,USION:

CLASSIFICATION:

I. STUDY DESIGN 

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DATA**EVALUATIO~** REPORT Cindy Schaffer, Micr-obiologist, SAB/HED

### C'" John Kouqh, Ph.D., l3iologist, SAB/HED\I\C_ 

### -1

__ _ Primary Eye Irritation-Rabbit (152A-14) 431115-01 Glioclad_ium virens GL-21 mycelium G-·7445.230 W.R. Grace & Co., Columbia, MD Microbioloqical Associates, Bethesda, MD Primary Eye Irritation Study of Gliocladium virens GL-21 in Rabbits. Martin L. Wenk, Ph.D., D.A.B.T. 4 November, 1993 Gliocladium virens GL-21 mycelium produced a slight ocular irritation (draize score 1.85 at 72 hours post dosing) when a sinqle 0.1 g dose
was administered. Ocular irritation dissipated 7 days post dosing. UNACCEPTABLE

- Since the end-use product was not used to evaluate eye irritation, S}I.B finds this study unacceptable. The registrant may be able to generate a r-ationale for lack of expected eye .Lrritation or physical eye injury from the end-use product. This information should be submitted for consideration.

Test Mat&.cicll: The microbial pest: control aqent (MPCA) is Gliocladium virens GL-21 mycelium in fermentation broth. The MPCA was administered undiluted at doses of 1.8 x 10' and 4 x 10' CFU/ml for the pretest and main test, respectively. Test Anim9JJe Six male Albino rabbits were obtained from Hazleton Research Products, Denver, PA. The rabbil:s weighed between 2. kq and 3 kq at the beginninq of the study.**MetJl.Q-'~'::** A sinqle 0.1 lUI dOSE' of the MPCA was administered into the evert:ed lower left eyelid of each animal. The eye was qently held toqether for 2 to 3 seconds to prevent a loss of material. The right eye served as the contr-ol for each animal. The Draize Method was used to score ocular lesions at 1 hour, and 1, 2, 3, 4 and 7 days post dosing. A 2% fluorescein solution was administered to evaluate corneal opacity of ulcerations by insertinq 1 drop into the cupped eye-sac and holding the lids together for 1 second. Corneal defects were illuminated with lonq-wave ultraviolet light. All animals were cbserved daily for morbibundity and mortalitl·EPA'sRecordsDispositionSchedulePEST361 ScientificDataReviewsHED RecordsCenter·File R141550·Page 6of 7

II. RESULTS: 

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A pretest screen was initially performed on one rabbit.. The main study evaluated the remaining five animals, both utilizing the test procedure above.

A. Pretest Screen: The treated eye displayed slight conjunctival erythema through 72 hours post dosing.

The cornea of both eyes stained with fluorescein: hours and the treated eye B. Main Study: TREATED EYES Conjunctivae

- Discharge: displayed opacity when the control eye at 24 through day 10.

Slight discharge was noted in 3 animals 1 hour post dosing. Swelling: One animal displayed slight swelling 1 hour post dosing. Redness: All animals displayed erythema 1 hour post dosing. One rabbit had slightly red eyes 24 hours post dosing. Cornea·· opaci

### ty: Two rabbits displayed slight corneal opacity in less than 1/4 of the eye area within 24 hours after dosing. One rabbit had slight corneal opacity in less than 1/4 of the eye at 48 hours post dosing. Three rabbits showed signs of corneal opacity in less than 1/4 of the eye at 72 hours post dosing. One rabbit had slight opacity in less than 1/4 of the cornea on day 4. UNTREATED EYES Two rabbits displayed corneal opacity 48 hours post dosing in less than 1/4 of the eye.
III. SAB DISCUSSION: Sliqht corneal opacity was obs,ervecl during the study but the frequency in control versus treated eyes was comparable. OveTa.Ll, Gliocladium vir-ens GL··21 mycelium produced a slight ocular irritation (average draize score of 1.85 at 72 hours) when a single 0.1 g ocular dose was administered. Ocular irritation was no longer present by day 7. SAB noted that the test material used in this study was not the same MPCA utilized in the end-use product. Therefore, this study is unacceptable as performed.EPA'sRecordsDispositionSchedulePEST361 ScientificDataReviewsHED RecordsCenter

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13,44



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Chemical Glincladilllll 'IrellsC··21


### I'eCode:

129000 liEDFileCode: 41500BPI'V'[m/Ch"1lI MemoVatl': 8/16/1994 Fik1Jl: DPD204818 DPD204820 AcccssioBI!: OOO-Oll-9002

HEDRecords**H:d('n'llc(~**Cen.er 4113/2007 

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