EPA's Records Disposition Schedule PEST 361 Scientific Data Reviews HED Records Center - File R141550 - Page 1 of 7 

SUBJECT: 

TO: 

FROM: 

THROUGH: 

• • 

UNITED STII,TES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 2()460 

OFFICE OF 

PREVENTION, PESTICIDES AND 

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 Gl iocladium 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 a Iso 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 submi tt'ed is suff icient to support an exempt ion from 

the requirement for a tolerance. 

Recycled/Recyclable 

PrInted wltlh SoylCanola Ink on paper thai 

contaIns at least 50% recycled fiber 
EPA's Records Disposition Schedule PEST 361 Scientific Data Reviews HED Records Center - File R141550 - Page 2 of 7 

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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's Records Disposition Schedule PEST 361 Scientific Data Reviews HED Records Center - File R141550 - Page 3 of 7 

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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: 

CLASSIF I C I'.'I'I ON : 

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. 

Teste Ma<:;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's Records Disposition Schedule PEST 361 Scientific Data Reviews HED Records Center - File R141550 - Page 4 of 7 

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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's Records Disposition Schedule PEST 361 Scientific Data Reviews HED Records Center - File R141550 - Page 5 of 7 

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 

• • 

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 rabbi l: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's Records Disposition Schedule PEST 361 Scientific Data Reviews HED Records Center· File R141550· Page 6 of 7 

II. RESULTS: 

• • 

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 s light 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's Records Disposition Schedule PEST 361 Scientific Data Reviews HED Records Center - File R141550 - Page 7 of 7 

13,44 

• 

R141550 

Chemical Glincladilllll 'Irells C··21 

I'e Code: 

129000 

liED File Code: 41500 BPI'V '[m/Ch"1lI 

Memo Vatl': 8/16/1 994 

Fik 1Jl: DPD204818 

DPD204820 

AcccssioBI!: OOO-Oll-9002 

HED Records H:d('n'llc(~ Cen.er 

4113/2007 

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