# US Environmental Protection Agency Office of Pesticide Programs

BIOPESTICIDES REGISTRATION ACTION DOCUMENT Gliocladium catenulatum strain J1446 
(PC Code 021009)


# November 12, 200 2BIOPESTICIDES REGISTRATION ACTION DOCUMENT 

### Gliocladium catenulatum strain J1446 (PC Code 021009)

U.S. Environm ental Protection Agency Office of Pesticide Programs Biopesticides and Pollut ion Prevention Division Gliocladium catenulatum strain J1446 (PC Code 021009)

Novem b er 12, 2002Gliocladium catenulatum strain J1446 Biopesticides Registration Action Docum e nt



### TABLE OF CONTENTS

I. ABSTRACT

................................................................. 1
II. OVERVIEW

................................................................ 1 A. Product Overview

...................................................... 1 B. Use Profile

............................................................. 1 C. Regulatory History

...................................................... 3
III. SCIENCE ASSESSMENT

..................................................... 3 A. Physical and Chemical Properties Assessment

............................... 3
B. Human Risk Assessment

........................................... 5 1. Human Toxicity Assessment

........................................ 5 a. Acute Toxicity

.............................................. 5 b. Subchronic Toxicity and Chronic Toxicity

...................... 6 2. Effects on the Immune and Endocrine Systems

......................... 6 3. Dose Response Assessment

.......................................... 7 4. Dietary Exposure and Risk Characteriz a tion

.......................... 7 5. Occupational, Residential, Sch ool and Day care Exposure and Risk Characteriz a tion

.............................................. 7 6. Drinking Water Exposure and Risk Characteriz a tion

................... 8 7. Acute and Chronic Dietary Risks for Sensitive Subpopulations Particularly Infants and Children

........................................... 9 8. Aggregate Exposure from Multiple Routes Including Dermal, Oral, and Inhalation

.................................................... 9 9. Cumulative Effects

................................................ 9 C. Environmental Assessment

.............................................. 1 0 1. Environmental Fate

.............................................. 1 0 2. Ecological Toxicity

............................................... 1 0 IV. RISK MANAGEMENT AND RE/REGISTRATION DECISION

................... 1 6 A. Determination of Eligibility

............................................. 1 6 iiGliocladium catenulatum strain J1446 Biopesticides Registration Action Docum e nt B. Regulatory Position

.................................................... 1 6 C. Labeling Rational

...................................................... 1 7 V. ACTIONS REQUIRED BY REGISTRANTS

.................................... 1 8 A. Precautionary Labeling

................................................. 1 8 B. Environmental Haz a rds Labeling

......................................... 1 8 1. End-Use Product Environmental Haz a rds Labeling

.................... 1 9 2. Manufacturing-Use Product Environmental Haz a rds Labeling

.......... 1 9 3. Application Rate

................................................. 1 9 C. Labeling

.............................................................. 1 9 BIBLIOGRAPHY

.............................................................. 2 1

iiiGliocladium catenulatum strain J1446 Biopesticides Registration Action Docum e nt I. ABSTRACT Gliocladium catenulatum strain J1446 is a naturally-occurring saprophytic fungus which is widespread in the environm ent. Gliocladium catenulatum can be cultured on various types of m e dia, where colonies range f r om whitish with pale-green centers on m a lt agar to grayish-green on oatm eal agar. This organism is the active ingredient of a m i crobial pesticide, PRIMASTOP Biofungicide. PRIMASTOP is used to control dam p ing-of f

, seed rot, root and stem rot, and wilt diseases caused by Rhizoctonia, Pythium, Phytophthora, Fusarium, Didymella, Botrytis, Verticillium, Alternaria, Cladosporium, Helminthosporium, Penicillium , and Plicaria

. The use of this product had been lim ited to greenhouse and indoor settings, but currently the product is also registered to be used outdoors on various vegetables, herbs, ornam e ntal pl ants, trees, shrubs and turf. No toxicological end-point of concern was identified. The health risk is expected to be m i nim a l for oral, derm al, and inhalation exposure routes. The risk to non-targetorganism s, including fish, birds, and insects, is expected to be m i nim a l.
II. OVERVIEW

A. Product Overview



### ! Microbial Pesticide Name: Gliocladium catenulatum strain J1446



### ! Trade Name: PRIMASTOP Biofungicide



### ! OPP Chemical Code : 021009



### ! Basic Manufacturer: Verdera Oy ( Form erly Kem i ra Agro Oy)



### ! US Agent: Ms. Kim Davis RegW est Com p any 30856 Rocky Road Greeley, CO 80631-9375

B. Use Profile Type of Pesticide: Fungicide Mechanism of action: The m ode of action is reported to be by an enzym a tic m echanism

. There are no reports indicating that Gliocladium catenulatum strain J1446 produces any toxins or antibiotics.

1Gliocladium catenulatum strain J1446 Biopesticides Registration Action Docum e nt Use Sites: At this tim e Gliocladium catenulatum J1446 is registered for greenhouse, indoor, and outdoor use. Greenhouse and Terrestrial Food Crops artichokes, asparagus, beans, beets, broccoli, brussel sprouts, cabbage, carrots, cauliflower, celery, chicory, chinese cabbage, corn, cucum b ers, eggplant, endive, garlic, horseradish, kale, kohlrabi, leeks, lentils, lettuce, m elons, New Zealand spinach, onions, parsnips, peas, peppers, potatoes, pum pkins, radishes, rutabagas, spinach, squash, strawberries, tom atoes, turnips, waterm elons, aniseed, basil, caraway, chives, dill, f e nnel, lavender, m a rjoram , oregano, parsley, rosem a ry, sage, savory, thym e, watercress Greenhouse, Indoor and Terrestrial Non-Food Sites ornam e ntals (including flowers, foliage and potted, bedding and seedling plants), tree shrub seedlings, and turf Target Pests for Active Ingredient: to control dam p ing-off, seed rot, root and stem rot, and wilt diseases caused by Rhizoctonia, Pythium, Phytophthora, Fusarium, Didymella, Botrytis, Verticillium, Alternaria, Cladosporium, Helminthosporium, Penicillium , and Plicaria Formulation Types Registered: Type: End-use product Form :wettable powder 37.0 % Gliocladium catenulatum strain J1446 Method and Rates of Application: Types of Treatm e nt soil incorporation, soil drench, foliar spray, and dipping of cuttings, bulbs, and tubers Equipm ent none specified Tim i ng at sowing, potting or transplanting and 2-6 weeks later for potted plants and 2-8 weeks later for other plants. Cuttings, bulbs, or tubers m a y be sprayed after planting or treated before planting or storage.

2Gliocladium catenulatum strain J1446 Biopesticides Registration Action Docum e nt Rates of Application: in soil: 0.05- 1.2 x10 8 CFU/L (0.05 -1.2 gram of PRIMASTOP/L of growth substrate) seedling trays or beds: 5- 25 x 10 8 CFU/m 2 (5- 25 gram of PRIMASTOP /m 2 ) foliar spray/ Field spraying and turf: 1 - 10 x10 8 CFU/m 2 (1- 10 gram PRIMASTOP/m 2 )
Method of Application : spray, incorporation in potting m e dia or bulb storage m i xture, bulb/tuber dipping

C. Regulatory History Kem i ra Agro Oy subm itted an application Decem ber 4, 1996 for registration of PRIMASTOP Biofungicide along with a pesticide petition which proposed establishing an exem ption from the requirem e nt of a tolerance for residues of the m i crobial pesticide, Gliocladium catenulatum strain J1446, on growing crops. On July 2, 1998 the PRIMASTOP Biofungicide product (EPA Reg. No. 64137-8) was registered only for greenhouse and indoor use sites. On May 16, 2000, an am endm ent was subm itted to add outdoor use sites and reduce the re-entry interval to zero hours. Consequently, the Agency has perform e d a com p lete ecological risk assessm ent for these new sites. This Biological Registration Action Decision docum ent includes the latest risk assessm ent inform ation. On June 19, 2002 the m a nufacturer, Kem i ra Agro Oy, changed its nam e to Verdera Oy.

III. SCIENCE ASSESSMENT A. Physical and Chemical Properties Assessment Product Identity: The agency has classified PRIMASTOP as a m i crobial fungicide. PRIMASTOP contains living Gliocladium catenulatum strain J1446 as the active ingredient. Gliocladium catenulatum is a naturally-occurring saprophytic fungus, which is widespread in the environm ent. The optim al growth conditions for the fungus include a tem p erature of 25- 28°C and an optim um pH of 5-6, with a range of pH 3-8.2. “ Colonies on m a lt agar (Oxoid) reaching 29 mm diam eter at 25°C, predom inately woolly, whitish, in the center pale gray-green; on oatm eal agar, 31 m m diam eter, elevated and m o re

3Gliocladium catenulatum strain J1446 Biopesticides Registration Action Docum e nt granular in the center, m o re pronounced grayish green and reverse slightly pinkish due to pigm ents in the subm erged my celium

. On Cherry decoction agar, sim ilar, also turning green rather rapidly.”

“ Conidiophores - penicillate, rather irregularly branched predom inating, but prim ary verticillate conidiophores also present. Phialides of penicillate conidiophores m o stly 12-17 μm long and approxim a tely 2.5 μm wide in the basal part.” “ Conidia- ellipsoidal, bilaterally sym m e trical, with an oblique scar of attachm e nt, m o stly 5.0-6.5 X 2.5-3.0 μm

. Chlamydospores m a y be present, term inal and intercalary, 7­ 10 μm diam eter.”

Product chem istry data which support the registration of Gliocladium catenulatum strain J1446 are sum m a rized in Table 1. Table 1. Physical and Chem ical Properties for Gliocladium catenulatum strain J1446

GUIDELINE Number STUDY RESULT MRID#

151A-10 P roduct Identity and Disclosure of Ingredients Acceptable 441893-01 441893-02 441893-03 151A-11 M anufacturing Process A cceptable 441893-04 151A-12 F orm a tion of Unintentional Ingredients G. catenulatum strain J1446 has not been reported to produce toxins. 441893-05

151A-13 A nalysis of Sam p les A cceptable 441893-06 151A-15 C ertification of Lim its Lim its listed in the CSF are adequate 441893-06

151A-16 P roduct Chem istry A cceptable 441893-07 441893-08 441893-09

4Gliocladium catenulatum strain J1446 Biopesticides Registration Action Docum e nt B. Human Risk Assessment There is a reasonable certainty that no harm will result from exposure to Gliocladium catenulatum strain J1446. This includes all anticipated dietary exposures and all other exposures for which there is reliable inform ation. 1. Human Toxicity Assessment

a. Acute Toxicity All m a m m a lian toxicology data requirem e nts have been subm itted and adequately satisfy data requirem e nts to support registration. The acute oral, acute pulm onary toxicity/pathogenicity, acute derm al irritation and acute eye irritation studies resulted in Toxicity Category IV classifications and indicated that the m i crobial pesticide is not pathogenic or infective in a single dose. The acute pulm onary toxicity/pathogenicity test resulted in a Toxicity Category III classification based upon the dose level. In the acute intra-peritoneal toxicity/pathogenicity study G. catenulatum strain J1446 dem onstrated no signs of toxicity or infectivity. Table 2. Toxicity Data Requirements GUIDELINE

NUMBER STUDY RESULT MRID#

152A-10 A cute Oral Toxicity/ Pathogenicity Acceptable, Toxicity Category IV 441893-10

152A-10 A cute Oral Toxicity/ Pathogenicity LD 50 of G. catenulatum strain J1446 in rats is >2000m g/kg. Acceptable, Toxicity Category III 441893-11

152A-11 A cute Derm al Irritation A cceptable, Toxicity Category IV 441893-12 152A-11 A cute Derm al Toxicity The LD 50 of G. catenulatum strain J1446 in rats is >2000m g/kg. Acceptable, Toxicity Category IV 442232-01

152A-12 A cute Pulm onary Toxicity/ Pathogenicity Acceptable, Toxicity Category III 441893-13

152A-12 A cute Pulm onary Toxicity The LC 50 of G. Catenulatum strain J1446 is > 5.57 m g /L in rats. Acceptable, Toxicity Category IV 441893-14

5Gliocladium catenulatum strain J1446 Biopesticides Registration Action Docum e nt
GUIDELINE

NUMBER STUDY RESULT MRID#

152A-13 A cute Intra-Peritoneal Toxicity/Pathogenicity Acceptable. The preparation produced inflam m a tion in unidentified parts of the rats, but there were not signs of infectivity or toxicity. 441893-15 444995-01

152A-14 A cute Eye Irritation A cceptable, Toxicity Category IV 441893-16 152A-15 B uehler Sensitization Test Supplem entary. Although not needed for hazard assessm ent, the results were m a rginal. The organism is not typically known to be a sensitizer. 441893-17

152A-16 H ypersensitivity Incidents - Hum a n Exposure No evidence of allergic reactions or other adverse effects in personnel working withG. catenulatum strain J1446 since 1991. Acceptable 441893-18

b. Subchronic Toxicity and Chronic Toxicity Subchronic and chronic toxicity were not required because survival, replication, infectivity, toxicity, or persistence of the m i crobial agent was not observed in the test anim als treated in the acute oral inf ectivity test. 2. Effects on the Immune and Endocrine Systems The Agency has no inform ation to suggest that Gliocladium catenulatum has an effect on the im m une and endocrine system s. No specific tests have been conducted with Gliocladium catenulatum strain J1446 to determ ine such effects. However, as is expected from a non-pathogenic m i croorganism , the subm itted toxicity/pathogenicity studies in rodents indicated that followi ng several routes of exposure, the im m une system is still intact and able to process and clear the active ingredient. There are no reports indicating that Gliocladium catenulatum strain J1446 produces any toxins or antibiotics. Therefore, it is unlikely that this organism would have estrogenic or endocrine effects because it is practically non-toxic to m a m m a ls.

6Gliocladium catenulatum strain J1446 Biopesticides Registration Action Docum e nt W h en the appropriate screening and or testing protocols being considered under the Agency’s Endocrine Disruptor Screening Program have been developed, Coniothyrium minitans strain CON/M/91-08 m a y be subjected to additional screening and/or testing to better characterize effects related to endocrine disruption. Based on the weight of the evidence of available data, no endocrine system -related effects have been identified. 3. Dose Response Assessment No toxicological endpoints are identified. 4. Dietary Exposure and Risk Characteriz a tion The use of Gliocladium catenulatum strain J1446 is not expected to result in any new dietary exposure to this organism . Fungi such as G. catenulatum strain J1446 are ubiquitous in the agricultural environm ent. It is anticipated that the concentrations of G. catenulatum on treated plants m a y be elevated im m e diately after application but will rapidly decline to environm ental background levels. The risks anticipated for dietary exposure are considered m i nim a l because no signs of toxicity were observed in the acute oral toxicity/pathogenicity studies. (Toxicity Category IV)
5. Occupational, Residential, Sch ool and Day care Exposure and Risk Characteriz a tion

a. Occupational Exposure and Risk Characterization
Derm al and inhalation exposure would be the prim ary routes of exposure for m i xer/loader applicators. Since unbroken skin is a natural barrier to m i crobial invasion of the hum an body, derm al absorption could occur only if the skin were cut, if the m i crobe were a pathogen equipped with m echanism s for entry through or infection of the skin, or if m e tabolites were produced that could be derm ally absorbed . Gliocladium catenulatum is not known to be a hum an pathogen nor is it known to produce m e tabolites that are derm ally absorbed. Since the intravenous study dem onstrated no adverse effects, it is the Agency' s opinion that even cut skin should not pose a risk to health if Gliocladium catenulatum strain J1446 was absorbed into the body via entry through a cut. Because the pulm onary study showed no adverse effects, the risks anticipated for inhalation exposure are considered m i nim a l. Based on the application m e thods listed on the product label, the potential for derm al, eye and inhalation exposures for pesticide handlers exists. Occupational exposure data, although not required, was provided. This data indicates that research with Gliocladium catenulatum J1446 biofungicide has continued at the Agricultural

7Gliocladium catenulatum strain J1446 Biopesticides Registration Action Docum e nt Research Centre since 1991 and at Kem i ra Agro Oy Espoo Research Centre since 1993. During these years, an average of 4 persons per year have worked with Gliocladium catenulatum J1446 biofungicide on a full-tim e basis, and 9 persons per year on a parttim e basis. There has been no evidence that the Gliocladium catenulatum J1446 biofungicide has caused allergic reactions or other adverse effects to the personnel involved in this work. There m a y be subpopulations yet to be identified that are prone to allergic reactions from frequent exposure to concentrated levels of G. catenulatum. The required personal protective equipm ent for applicators and handlers is expected to adequately reduce inhalation or derm al exposure to this m i crobial pesticide. Occupational exposures and subsequent risks are negligible because the organism has been determ ined not to be pathogenic to hum ans. and anim als. The risks are expected to be m i nim a l based on evaluations of subm itted Tier I acute toxicity tests (Table 2). b. Residential, School and Day Care Exposure and Risk Characterization Other non-occupational exposure of Gliocladium catenulatum strain J1446 via residential and indoor uses of it as a pesticide, e.g., uses around hom es, parks, recreation areas, will be m i nim a l to non-existent. The risk from non-occupational exposure is considered m i nim a l as there is no evidence of adverse effects from oral, derm al or inhalation exposure to this m i crobial agent.

. 6. Drinking Water Exposure and Risk Characteriz a tion Gliocladium catenulatum strain 1446 is a naturally-occurring m i croorganism and is widespread in the environm ent throughout the world. Gliocladium catenulatum is not known as an aquatic fungus, and therefore is not expected to proliferate in aquatic habitats. Moreover, the risk from non-occupational exposure is considered m i nim a l as there is no evidence of adverse effects from oral, derm al or inhalation exposure to this m i crobial agent. Drinking water is accordingly not being screened for Gliocladium catenulatum as a potential indicator of m i crobial contam ination or as a direct pathogenic contam inant. Both percolation through soil and m unicipal treatm e nt of drinking water would reduce the possibility of exposure to Gliocladium catenulatum through drinking water. Therefore, the pot ential of significant transfer to drinking water is m i nim a l to nonexistent. In addition, the risk from consum ption of drinking water containing Gliocladium catenulatum is considered m i nim a l as there is no evidence of adverse effects from oral exposure to this m i crobial agent.

8Gliocladium catenulatum strain J1446 Biopesticides Registration Action Docum e nt 7. Acute and Chronic Dietary Risks for Sensitive Subpopulations Particularly Infants and Children There have been no confirm e d reports of im m e diate or delayed allergic reactions to Gliocladium catenulatum strain 1446

. Based on the acute toxicity inform ation discussed above, EPA concludes that there is a reasonable certainty that no harm will result from aggregate exposure to the United States population, including infants and children, to residues of Gliocladium catenulatum strain J1446 . This includes all anticipated dietary exposures and all other exposures for which there is reliable inform ation. The Agency has arrived at this conclusion because, as discussed in Unit B. Hum a n Risk Assessm ent, Gliocladium catenulatum strain J1446 is practically non-toxic to m a m m a ls and under reasonably foreseeable circum stances it does not pose a risk. FFDCA section 408 provides that EPA shall apply an additional ten-fold m a rgin of exposure (safety) for infants and children in the case of threshold effects to account for pre- and post-natal toxicity and the com p leteness of the database, unless EPA determ ines that a different m a rgin of exposure (safety) will be safe for infants and children. Margins of exposure (safety) are often referred to as uncertainty (safety) factors. In this instance, the Agency believes there is reliable data to support the conclusion that Gliocladium catenulatum strain J1446 is practically non-toxic to m a m m a ls, including infants and children, and, thus, there are no threshold effects; therefore, EPA has not used a m a rgin of exposure (safety) approach to assess the safety of Gliocladium catenulatum strain J1446 . As a result, the provision requiring an additional m a rgin of exposure (safety) does not apply. 8. Aggregate Exposure from Multiple Routes Including Dermal, Oral, and Inhalation The health risk is expected to be negligible for oral, derm al, and inhalation exposure routes, as stated above. The potential aggregate exposure, derived from derm al and inhalation exposure via m i xing, loading and applying Gliocladium catenulatum Strain 1446, the dietary exposure from drinking wa ter and treated produce containing this organism , should fall well below the currently tested m i crobial safety levels. In sum m a ry, the potential aggregate exposure, derived fromnon-dietary and nonoccupational exposure, should be m i nim a l. 9. Cumulative Effects Gliocladium catenulatum strain J1446 is practically non-toxic to m a m m a ls. No

9Gliocladium catenulatum strain J1446 Biopesticides Registration Action Docum e nt

m echanism of toxicity in m a m m a ls has been identified for this organism

. Therefore no cum u lative effect with other related organism s is anticipated. C. Environmental Assessment 1. Environmental Fate

Environm ental fate studies are not required at this tim e since no adverse risks were triggered in Tier I Non-target Organism s Studies. Gliocladium catenulatum strain J1446 is a naturally occurring saprophytic soil fungus; as a species, it is found throughout the world in a variety of soil types, without pathogenic incidence to plant or anim al. The ubiquitous nature of the organism suggests that the environm ental burden is not likely to increase substantially to pose adverse risks to nontarget organism s as a result of the intended outdoor uses. There were no incidents of pathogenicity or toxicity by G. catenulatum to non-target organism s in the literature searches provided. Estimated Environmental Concentration of Gliocladium catenulatum Cell Mass: Based on the intended rates of application, the estim ated environm ental concentration of Gliocladium catenulatum Cell Mass is not anticipated to exceed ~ 500 m g /L for soil incorporation applications; and ~200 m g /L for soil drench applications.

2. Ecological Toxicity Results of non-target avian, freshwater fi sh, daphnia, honey bee and beneficial insect studies subm itted to the Agency generally dem onstrated a lack of toxicity or pathogenicity to the indicator species. Results of these studies indicate that m i nim a l toxic or pathogenic effects to terrestrial or freshwater wildlife ar e expected from currently intended applications of Gliocladium catenulatum cell m a ss. Sum m a ries and conclusions of these studies are presented below.
Table 3: Eco-Toxicology Sum m a ry

10Gliocladium catenulatum strain J1446 Biopesticides Registration Action Docum e nt

Guideline No. Study S tatus, Classification & Comments MR I D #

154-16 *885-4050 Avian oral toxicity/ pathogenicity ACCEPTABLE. The no observed effect dosage of Gliocladium catenulatum cell m a ss was determ ined at approxim a tely 1.4 × 10 6 cfu/g body weight for five days. This study showed a lack of toxicity or pathogenicity of Gliocladium catenulatum cell m a ss to northern bobwhite quail. 445014-01

154-19 *885-4200 Fresh water fish toxicity/ pathogenicity ACCEPTABLE. The LC 50 was calculated as 504 m g /L (3.5×10 8 cfu/L). This study is scientifically valid, satisfies current guideline requirem e nts 445014-02

154-20 *885-4240 Fresh water aquatic invertebrate toxicity/pathogenicity ACCEPTABLE. Under static-renewal conditions, the 21-day EC 50 value was 7.8 m g /L (5.5 x 10 6 cfu/L). The LOEC and the NOEC were 11 m g /L and 5.6 m g /L, respectively. The pathogenicity of Gliocladium catenulatum was not evaluated in this study. 445014-03

154-22 *885-4300 Nontarget plant toxicity/pathogenicity W A IVED. In the literature review subm itted, there were no reports of pathogenicity to plants. The literature review satisfies current guidelines for non-target plant testing and m a y be used as the basis for waiving further non-target plant tests, pending appropriate product characterization and taxonom ic verification. 441893-20

11Gliocladium catenulatum strain J1446 Biopesticides Registration Action Docum e nt

Guideline No. Study S tatus, Classification & Comments MR I D #

154-23 *885-4340 Nontarget insect toxicity/pathogenicity Green Lacewing : ACCEPTABLE. The dietary LC 50 value for green lacewing larvae exposed to G

. catenulatum cell m a ss for 12 days is presum ed greater than 5200 ppm (3.6×10 6 CFU/g) and the no observed effect concentration is ~5200 ppm (3.6×10 6 CFU/g). This study showed a lack of toxicity of Gliocladium catenulatum cell m a ss to green lacewings. There were no evaluations of infectivity or pathogenicity. Parasitic Hymenoptera ACCEPTABLE. The dietary LC50 value for parasitic Hym e noptera exposed to G

. catenulatum cell m a ss for eight days was calculated approxim a tely 1992 ppm (1.4×10 6 CFU/m L ) and the no observed effect concentration determ ined to be 520 ppm (3.6×10 5 CFU/m L ). This study showed a lack of toxicity of Gliocladium catenulatum cell m a ss to parasitic Hym e noptera. There were no evaluations of infectivity or pathogenicity.
Ladybird Beetles ACCEPTABLE. The dietary LC50 value for ladybird beetles exposed to G

. catenulatum cell m a ss for 16 days is estim ated to be greater than 5200 ppm (3.6×10 6 CFU/m L ), the highest concentration tested, and the no observed effect concentration to be 520 ppm (3.6×10 5 CFU/m L ). An LD 50 >3.6×10 6 CFU/m L and an NOEL of 3.6×10 5 CFU/m L was reported. This study showed a lack of toxicity of Gliocladium catenulatum cell m a ss to lady beetles. There were no evaluations of infectivity or pathogenicity. 445014-04

445014-05

445014-06

154-24 *885-4380 Honeybee toxicological/pathogenicity ACCEPTABLE. Reported bee m o rtalities were not dose-responsive nor statistically significant. Therefore the dietary LC 50 value for honey bees exposed to G

. catenulatum cell m a ss for 10 days is estim ated to be greater than 5200 ppm (3.6×10 6 CFU/m L ), the highest concentration tested, and the no observed effect concentration is estim ated to be 5200 ppm (3.6×10 6 CFU/m L ). An LD 50 value >3.6×10 6 CFU/m L and an NOEL of 3.6×10 5 CFU/m L were reported. 445014-07

12Gliocladium catenulatum strain J1446 Biopesticides Registration Action Docum e nt *885 series = OPPTS Microbial Pesticide Test Guideline Numbers.

a. Toxicity to Terrestrial Animals (i) Avian Species: Acute Toxicity/Pathogenicity : Under conditions of the reported study (MRID# 445014-01) , no adverse effects were exhibited by juvenile northern bobwhite after 30 days when adm i nistered (by oral gavage) daily doses of 1 × 10 4 Gliocladium catenulatum -cfu/g body weight/day for a five day period. This dosage is approxim a tely equivalent to a total dosage of 7 × 10 6 cfu/g body weight for 5 days. The no observed effect dosage of Gliocladium catenulatum cell m a ss was determ ined at approxim a tely 1.4 × 10 6 cfu/g body weight for five days. There were no evidences of test substance replication, lesions, plaques or other indications of infectivity or pathogenicity for the groups treated with Gliocladium catenulatum cell m a ss in gross necropsies. This study showed a lack of toxicity or pathogenicity of Gliocladium catenulatum cell m a ss to northern bobwhite quail. This study is scientifically valid, satisfies current guideline requirem e nts, and is acceptable for assessing short-term toxic and pathogenic effects of Gliocladium catenulatum Strain J1446 to terrestrial avian species. (ii) Wild Mammals and Other Terrestrial Animals: Acute Toxicity/Pathogenicity : b. Toxicity to Aquatic Animals (i) Freshw ater Fish : Under static-renewal conditions, the no-observed effect concentration was 179 m g /L (1.3×10 8 cfu/L) for juvenile rainbow trout dual-exposed via aqueous test solutions and in a daily diet for 30 days. The no m o rtality concentration was 357 m g /L (2.5×10 8 cfu/L). The LC 50 was calculated as 504 m g /L (3.5×10 8 cfu/L). There were no signs of infection in fish tissues exam ined for necropsy, and all appeared internally and externally norm a l. Gliocladium catenulatum was isolated from the heart, liver and brain sam p les of fish treated with 179 m g /L test substance; and from the kidney, heart, liver and brain sam p les of fish treated with 357 m g /L test substance. Although the test substance was present, target organs did not appear to be affected, and there were no apparent effects upon the health of the fish. This study (MRID# 445014-02) is scientifically valid, satisfies current guideline requirem e nts, and is acceptable for assessing short-term toxic and pathogenic effects of Gliocladium catenulatum Strain J1446 to freshwater fish.
13Gliocladium catenulatum strain J1446 Biopesticides Registration Action Docum e nt (ii) Freshwater Aquatic Invertebrate Under static-renewal conditions, the 21-day EC 50 value for survival of neonate Daphnia magna exposed aqueously to Gliocladium catenulatum was 7.8 m g /L (5.5 x 10 6 cfu/L). The LOEC and the NOEC were 11 m g /L and 5.6 m g /L, respectively. Of the three param e ters assessed (survival, growth and reproduction), reproduction proved to be the m o st sensitive param e ter. The EC 50 value was 7.8 m g /L (~5.5 x 10 6 cfu/L); and the NOEC and the LOEC were 2.8 (2.0 x 10 6 cfu/L) and 5.6 m g /L (3.9 x 10 6 cfu/L), respectively. This study (MRID# 445014-03) is scientifically valid, satisfies current guideline requirem e nts, and is acceptable for assessing short-term toxic effects of Gliocladium catenulatum Strain J1446 to aquatic invertebrates. The pathogenicity (or infectivity) of Gliocladium catenulatum was not evaluated in this study.

c. Toxicity to Plants A review of the literature resulted in the utility of Gliocladium catenulatum to control plant diseases caused by other fungi, Rhizoctonia , Pythium , Botrytis , Fusarium , Didymella , Verticillium , Alternaria , Cladosporium , Helminthosporium , Penicillium and Pilcaria

. There were no reports of pathogenicity to plants. Therefore, G. catenulatum is not expected to cause adverse effects to nontarget plants. The literature review (MRID # 441893-20) satisfies current guidelines for non-target plant testing and m a y be used as the basis for waiving further non-target plant tests, pending appropriate product characterization and taxonom ic verification.
d. Toxicity/Pathogenicity to Honeybees and Nontarget Insects Honey Bees : This study (MRID# 445014-07) was conducted in com p liance with Good Laboratory Practice Standards as published by the U.S. Environm ental Protection Agency, Office of Pesticide Program s in 40 CFR Part 160. Reported bee m o rtalities were not dose-responsive nor statistically significant. Therefore the dietary LC 50 value for honey bees exposed to G

. catenulatum cell m a ss for 10 days is estim ated to be greater than 5200 ppm (3.6×10 6 CFU/m L ), the highest concentration tested, and the no observed effect concentration is estim ated to be 5200 ppm (3.6×10 6 CFU/m L ).

14Gliocladium catenulatum strain J1446 Biopesticides Registration Action Docum e nt An LD 50 value >3.6×10 6 CFU/m L and an NOEL of 3.6×10 5 CFU/m L were reported. This study showed a lack of toxicity of Gliocladium catenulatum cell m a ss to honey bees. Mortalities were theref ore presum ed to be associated with other environm ental variables associated with the test arena. There were no evaluations of infectivity or pathogenicity. This study is scientifically valid, satisfies current guideline requirem e nts, and is acceptable for assessing short-term toxic effects of Gliocladium catenulatum Strain J1446 to honey bees. Green Lacew ing: The rates of m o rtality and pupation were sim ilar in the treatm e nt groups as in the untreated control group. Reported m o rtalities were not treatm e nt related. Therefore, the dietary LC 50 value for green lacewing larvae exposed to G

. catenulatum cell m a ss for 12 days is presum ed greater than 5200 ppm (3.6×10 6 CFU/g) and the no observed effect concentration is ~5200 ppm (3.6×10 6 CFU/g). This study (MRID# 445014-04) showed a lack of toxicity of Gliocladium catenulatum cell m a ss to green lacewings. There were no evaluations of infectivity or pathogenicity. This study is scientifically valid, satisfies current guideline requirem e nts, and is acceptable for assessing short-term toxic effects of Gliocladium catenulatum Strain J1446 to green lacewings. Parasitic Hymenoptera : Mortalities were related to the test substance in one group--treated with 5,200 ppm G. catenulatum cell m a ss. Therefore the dietary LC50 value for parasitic Hym e noptera exposed to G

. catenulatum cell m a ss for eight days was calculated approxim a tely 1992 ppm (1.4×10 6 CFU/m L ) and the no observed effect concentration determ ined to be 520 ppm (3.6×10 5 CFU/m L ). This study (MRID# 445014-05) showed a lack of toxicity of Gliocladium catenulatum cell m a ss to parasitic Hym e noptera. There were no evaluations of infectivity or pathogenicity. This study is scientifically valid, satisfies current guideline requirem e nts, and is acceptable for assessing short-term toxic effects of Gliocladium catenulatum Strain J1446 to parasitic wasps. Lady Beetles : Mortalities were not dose-responsive, nor associated with Gliocladium catenulatum cell m a ss . Therefore the dietary LC50 value for ladybird beetles exposed to G

. catenulatum cell m a ss for 16 days is estim ated to be greater than 5200 ppm (3.6×10 6 CFU/m L ), the highest concentration tested, and the no observed effect concentration to be 520 ppm (3.6×10 5 CFU/m L ). An LD 50 >3.6×10 6 CFU/m L and an NOEL of 3.6×10 5 CFU/m L was reported.

15Gliocladium catenulatum strain J1446 Biopesticides Registration Action Docum e nt This study showed a lack of toxicity of Gliocladium catenulatum cell m a ss to lady beetles. There were no evaluations of infectivity or pathogenicity. This study (MRID# 445014-06) is scientifically valid, satisfies current guideline requirem e nts, and is acceptable for assessing short-term toxic effects of Gliocladium catenulatum Strain J1446 to ladybird beetles.
IV. RISK MANAGEMENT AND RE/REGISTRATION DECISION A. Determination of Eligibility

Section 3(c)(5) of FIFRA provides for the registration of new active ingredients if it is determ ined that (A) its com position is such as to warrant the proposed claim s for it; (B) its labeling and other m a terials required to be subm itted com p ly with the requirem e nts of FIFRA; (C) it will perform its intended functi on without unreasonable adverse effects on the environm ent; and (D) when used in accordance with widespread and com m only recognized practice, it will not generally cause unreasonable adverse ef f ects on the environm ent. To satisfy criterion "A" above, Gliocladium catenulatum strain J1446 has well known properties. The Agency has no knowledge that would contradict the claim s m a de on the label of this product. Criterion "B" is satisfied by the current label and by the data presented in this docum ent. It is believed that this new pesticidal active ingredient will not cause any unreasonable adverse effects, is a broad sp ectrum m i crobial fungicide, and does provide protection as claim e d satisfying criterion "C". Criterion "D" is satisfied in that Gliocladium catenulatum strain J1446 is not expected to cause unreasonable adverse effects when used according to label instructions. Therefore, Gliocladium catenulatum strain J1446 is eligible for registration. The uses are listed in the Section II, B. Use Prof ile.
B. Regulatory Position 1. Unconditional Registration The data requirem e nts are f u lf illed and the Biopesticides and Pollution Prevention Division recom m e nds unconditional registration of the product containing Gliocladium catenulatum strain J1446 as the sole Active ingredient (PRIMASTOP). 2. Tolerances for Food Uses and /or exem ptions EPA received a pesticide petition (PP 7F806) from Kem i ra Agro Oy, proposing

16Gliocladium catenulatum strain J1446 Biopesticides Registration Action Docum e nt [pursuant to section 408(d) of the Federal Food, Drug and Cosm etic Act, 21 U.S.C. section 346a(d)], to am end 40 CFR part 180 by establishing an exem ption from the requirem e nt of a tolerance for residues of the m i crobial pesticide, Gliocladium catenulatum strain J1446, on growing crops. EPA issued a notice establishing an exem ption from the requirem e nts of a tolerance for residues of Gliocladium catenulatum strain J1446 in or on all food comm odities. 3. CODEX Harm onization There are no CODEX values for Gliocladium catenulatum strain J1446 . 4. Risk Mitigation Since there are no risk issues, no risk m itigation m easures are required at this tim e f o r dietary risk, occupational and residential risk, or ground and surface water contam ination for Gliocladium catenulatum strain J1446 .
5. Endangered Species Statem ent Im pacts to endangered species from intended exposures of Prim astopTM are anticipated to be negligible or nonexistent. This assessm ent is prem ised upon a com b ination of several factors: (1) low estim ated environm ental concentration values; (2) data and evidence f r om the public literature as sum m a rized in the Environmental Fate portion of this assessm ent; and (3) the practically nontoxic (and non-infective) status of the MPCA in surrogate toxicity/pathogenicity studies summ a rized in the Ecological Effects portion of this assessm ent.

C. Labeling Rational 1. Hum a n Health Hazard (W PS and non-W PS) Gliocladium catenulatum strain J1446 products with com m e rcial use sites are subject to the W o rker Protection Standard. Because of the low toxicity of Gliocladium catenulatum strain J1446 , the Re-Entry Interval for uses within the scope of W PS is zero hours. Precautionary statem ents and personal protective equipm ent as specified below are required based on the acute toxicity categories of this organism

. 2. Environm ental Hazard

17Gliocladium catenulatum strain J1446 Biopesticides Registration Action Docum e nt Precautionary labeling is required as indicated below.

V. ACTIONS REQUIRED BY REGISTRANTS A. Precautionary Labeling Gliocladium catenulatum strain J1446 products m u st state the following under the heading “Precautionary Statem ents”: Caution. Harm ful if swallowed or inhaled. A void breathing dust or spray m i st. W a sh thoroughly with soap and water after handling. Rem ove contam inated clothing and wash before reuse. Personal Protective Equipm ent required for Applicators and other handlers m u st wear: Long sleeved shirt and long pants. W a terproof gloves. Shoes plus socks. A NIOSH approved respirator with any N, P, R, or HE f ilter.”
W PS labels m u st state the following under the heading “User Safety Recomm e ndations” Users should wash hands before eating, drinki ng, chewing gum , using tobacco, or using the toilet. Users should rem ove clothing im m e diately if pes ticide gets inside. Then wash thoroughly and put on clean clothing. Users should rem ove PPE im m e diately after handli ng this product. If gloves are worn, wash the outside of gloves before rem oving. As soon as possible, wash thoroughly and change into clean clothing.

B. Environmental Haz a rds Labeling Provided the following statem ent is placed into the environm ental hazards statem ent, the risk of Gliocladium catenulatum strain J1446 is m i nim a l to nonexistent to non-target organism s including endangered species. 1. End-Use Product Environmental Haz a rds Labeling "Do not apply directly to water, or to areas where surface water is present or to intertidal

18Gliocladium catenulatum strain J1446 Biopesticides Registration Action Docum e nt

areas below the m ean high water m a rk. Do not contam inate water by cleaning of equipm ent or disposal of equipm ent washwaters. "

2. Manufacturing-Use Product Environmental Haz a rds Labeling "Do not discharge effluent containing this product into lakes, stream s, ponds, estuaries, oceans, or public water unless this product is specifically identified and addressed in an NPDES perm it. Do not discharge effluent containing this product to sewer system s without previously notifying the sewage treatm e nt plant authority. For guidance, contact your State W a ter Board or Regional Office of the EPA." 3. Application Rate It is the Agency' s position that the labeling for the pesticide products containing Gliocladium catenulatum strain J1446 as the active ingredient com p lies with the current pesticide labeling requirem e nts. The Agency has not required a m a xim u m num ber of applications per a season of this active ingredient. C. Labeling The attached label for PRIMASTOP Biofungicide Powder (EPA Reg. No. 64137-8) conform s with the labeling requirem e nts for Gliocladium catenulatum strain J1446 . Som e of the essential label requirem e nts are highlighted below. Signal word is "Caution," based on (toxicity category III). The product shall contain the f o llowing inf o rm ation:

- P roduct Nam e

- I ngredient Statem ent

- R egistration Num b er

- " Keep Out of Reach of Children"

- S ignal W ord (CAUTION)

- P ersonal Protective Equipm ent (PPE) Requirem ents

- E nvironm ental Hazard Statem ent

- S torage and Disposal Statem ent

- A gricultural Use Requirem ents

- N on-Agricultural Use Requirem ents

- D irections for Use

19Gliocladium catenulatum strain J1446 Biopesticides Registration Action Docum e nt BIBLIOGRAPHY : Citations Considered to be part of the Data Base Supporting the Registration of Gliocladium catenulatum strain J1446. 44189300 Kem i ra Agro Oy (1996) Subm ission Product Chem istry, Toxicity, Hazard to Non-Target Organism s and Environm ental Fate Data in Support of the Application for Registration of PRIMASTOP Biofungicide (Gliocladium catenulatum Strain J1446). Transm ittal of 22 Studies. 44189301 Mohamm a di, O. (1996) Product Identification a nd Disclosure of Ingredients Gliocladium catenulatum Strain J1446. Unpublished study prepared by Kem i ra Agro Oy. 14 p. 44189302 Gam s , W

. (1996) Independent Third Party Iden tification of Gliocladium catenulatum Strain J1446: Lab Project Num b er: DET 225 (1996). Unpublished study prepared by Centraalbureau Voor Schimm e lcultures (CBS), Institute of the R oyal Netherlands Academ y of Arts and Science. 6 p. 44189303 Yli-Mattila, T. (1996) Identification of J1446 Strain by RAPD-PCR Analysis. Unpublished study prepared by University of Turku. 23 p. 44189304 Tuom inen, U. (1996) Gliocladium catenulatum Stra in J1446: Description of Beginning Materials and Manufacturing Process. Unpublished study prepared by Kem i ra Agro Oy. 50 p. 44189305 Mohamm a di, O.; Lahdenpera, M.; Tuom inen, U. (1996) Gliocladium catenulatum Strain J1446 Biofungicide: Discussion of the Form ation of Im purities. Unpublished study prepared by Kem i ra Agro Oy. 65 p. 44189306 Tuom inen, U. (1996) Prelim inary Analysis, Cer tification of Ingredient Lim its, and Analytical Methods: Gliocladium catenulatum Strain J1446. Unpublished study prepared by Kem i ra Agro Oy. 13 p. 44189307 Jacobs, R.; Markley, B. (1996) Product Chem istr y Testing of the Active Ingredient (A.I.) in Gliocladium Biofungicide: Color, Physical St ate, Odor, Bulk Density and pH: Lab Project Num b er: 293C-101. Unpublished study prepared by W ildlife International Ltd. 22 p. 44189308 Jacobs, R.; Markley, B. (1996) Product Chem istry Testing of Gliocladium Biofungicide Powder: Color, Physical State, Odor, Bulk Density and pH: Lab Project Num b er: 293C-102. Unpublished study prepared by W ildlife International Ltd. 22 p. 44189309 Jacobs, R.; Markley, B. (1996) Product Chem istry Testing of Gliocladium Biofungicide Powder: Corrosion Characteristics: Lab Project Num b er: 293C-103. Unpublished study prepared by W ildlife International Ltd. 16 p. 44189310 McRae, L. (1996) Acute Oral Toxicity and Pa thogenicity to the Rat: Gliocladium catenulatum Cell Mass: Lab Project Num b er: RKY 135/961805/AC. Unpublished study prepared by Huntingdon Life Sciences Ltd. 31 p. 44189311 W ilson, J. (1995) Gliocladium (J1446) Preparation: Acute Oral Toxicity (Lim it) Test in Rats: Lab Project Num b er: 556576: 10919. Unpublished st udy prepared by Inveresk Research International. 27 p. 44189312 W ilson, J. (1995) Gliocladium (J1446) Preparation: Acute Derm al Irritation Test in Rabbits: Lab
20Gliocladium catenulatum strain J1446 Biopesticides Registration Action Docum e nt Project Num b er: 556576: 10921. Unpublishe d study prepared by Inveresk Research International. 25 p. 44189313 McRae, L. (1996) Acute Pulm onary Toxicity and Pathogenicity to Rat: Gliocladium catenulatum Cell Mass: Lab Project Num b er: RKY 137/961808/AC. Unpublished study prepared by Huntingdon Life Sciences Ltd. 44 p. 44189314 Kieran, P. (1995) Gliocladium (J1446) Preparati on: Acute Inhalation Toxicity (Lim it) Test in Rats: Lab Project Num b er: 654570: 10916. Unpublished study prepared by Inveresk Research International. 40 p. 44189315 McRae, L. (1996) Acute Intra-Peritoneal Toxic ity and Pathogenicity to the Rat: Gliocladium catenulatum Cell Mass: Lab Project Num b er: RKY 136/961807/AC. Unpublished study prepared by Huntingdon Life Sciences Ltd. 35 p. 44189316 W ilson, J. (1995) Gliocladium (J1446) Preparation: Acute Eye Irritation Test in Rabbits: Lab Project Num b er: 556576: 10922. Unpublished study prep ared by Inveresk Research International. 27 p. 44189317 W ilson, J. (1995) Gliocladium (J1446) Preparati on: Buehler Sensitisation Test in Guinea Pigs: Lab Project Num b er: 556576: 10923. Unpublis hed study prepared by Inveresk Research International. 33 p. 44189318 Mohamm a di, O. (1996) Gliocladium catenulat um Strain J1446 Biofungicide Hypersensitivity Incident Reporting. Unpublished study prepared by Kem i ra Agro Oy. 4 p. 44189319 Mohamm a di, O. (1996) Gliocladium catenulatum Strain J1446--Literature Search, Avian and Aquatic. Unpublished study prepared by Kem i ra Agro Oy. 11 p. 44189320 Mohamm a di, O. (1996) Gliocladium catenulat um --Literature Search, Nontarget Plants. Unpublished study prepared by Kem i ra Agro Oy. 23 p. 44189321 Mohamm a di, O. (1996) Gliocladium catenulatum --Literature Search, Nontarget Insects. Unpublished study prepared by Kem i ra Agro Oy. 6 p. 44189322 Tuom inen, U. (1996) Storage Stability: Glioclad ium catenulatum Strain J1446. Unpublished study prepared by Kem i ra Agro Oy. 4 p. 44223201 W ilson, J. (1995) Gliocladium (J1446) Preparation: Acute Derm al Toxicity (Lim it) Test in Rabbits: Lab Project Num b er: 10920: 556576: IRI 556576. Unpublished study prepared by Inveresk Research International. 26 p. 44499501 McRae, L. (1998) Response to Questions Ra ised by EPA Regarding MRID Num b er 44189315 Entitled “Acute Intra-Peritoneal Toxicity and Pathogenicity to the Rat: Gliocladium catenulatum Cell Mass” Unpublished study prepared by Huntingdon Life Sciences Ltd. 16 p. 44501400 Kem i ra Agro Oy (1998) Subm ission of Toxi city Data in Support of the Application for Registration of Prim astop. Transm ittal of 7 Studies. 44501401 Foster, J.; Grim es, J.; Beavers, J. (1997) G liocladium catenulatum Cell Mass: An Avian Oral
21Gliocladium catenulatum strain J1446 Biopesticides Registration Action Docum e nt Pathogenicity and Toxicity Study in the Northern B obwhite: Lab Project Num b er: 293-109. Unpublished study prepared by W ildlife International Ltd. 42 p. 44501402 Palm er, S.; Krueger, H. (1998) Glioclad ium catenulatum Cell Mass (Technical Product): A Five-Concentration Toxicity and Pathogenicity Test with the Rainbow Trout (Oncorhynchus m ykiss): Final Report: Lab Project Nu m

b er: 293A-104. Unpublished study prepared by W ildlife International Ltd. 41 p. 44501403 Palm er, S.; Krueger, H. (1998) Gliocladium catenulatum Cell Mass (Technical Product): A 21-Day Life-Cycle Toxicity and Pathogenicity Test with the Cl adoceran (Daphnia m a gna): Final Report: Lab Project Num b er: 293A-103. Unpublished study prepared by W ildlife International Ltd. 43 p. 44501404 Hoxter, K.; Palm er, S.; Krueger, H. (1998) Gliocladium catenulatum Cell Mass (Technical Product): A Dietary Pathogenicity and Toxicity Study with Green Lacewing Larvae (Chrysoperia carnea): Lab Project Num b er: 293-113A. Unpublishe d study prepared by W ildlife International Ltd. 22 p. 44501405 Hoxter, K.; Palm er, S.; Beavers, J. (1998) Gliocladium catenulatum Cell Mass (Technical Product): A Dietary Pathogenicity and Toxic ity Study with Parasitic Hym e noptera (Nasonia vitripennis): Lab Project Num b er: 293-112. Unpub lished study prepared by W ildlife International Ltd. 24 p. 44501406 Hoxter, K.; Palm er, S.; Krueger, H. (1998) Gliocladium catenulatum Cell Mass (Technical Product): A Dietary Pathogenicity and Toxicity Study with the Ladybird Beetle (Hippodam i a convergens): Lab Project Num b er: 293-111. Unpublished study prepared by W ildlife International Ltd. 25 p. 44501407 Hoxter, K.; Palm er, S.; Krueger, H. (1998) Gliocladium catenulatum Cell Mass (Technical Product): A Dietary Pathogenicity and Toxicity Study with the Honey Bee (Apis m e llifera): Lab Project Num b er: 293-110. Unpublished study prepared by W ildlife International Ltd. 24 p.

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