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EPA BIOPESTICIDES AND POLLUTI ON PREVENTION DIVISION

COMPANY NOTICE OF FILING FOR PE STICIDE PETITIONS PUBLISHED IN

THE FEDERAL REGISTER

Marrone Bio Innovations

0F7681

EPA has received a pesticide petition 0F7681 from Marrone Bio Innovations, proposing, pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CF R part 180 to establish an exemption from the requirement of a tolerance for the microbial pesticide Streptomyces acidiscabies

strain RL-110 T

Pursuant to section 408(d)(2)( A)(i) of FFDCA, as amended, Marrone Bio

Innovations has submitted the following summary of information, data, and arguments in support of their pesticide petition. This summary was prepared by Marrone Bio

Innovations and EPA has not fully evaluated the merits of the pesticide petition. The summary may have been edited by EPA if the terminology used was unclear, the summary contained extraneous material, or the summary unintentiona lly made the reader conclude that the findings reflected EPA’s position and not the position of the petitioner.

I. Marrone Bio Innovations Petition Summary

0F7681

A. Product Name and Proposed Use Practices

MBI-005 TGAI is a highly selective bi ological herbicide containing killed, nonviable Streptomyces acidiscabies strain RL-110 T cells. MBI-005 controls pre-emergent and post-emergent broadleaf and sedge weeds in cereal grains, corn, sugarcane and turf. For pre-emergent control, MBI-005 should be applied to the soil pr ior to weed and crop emergence. For post-emergent control, appl y MBI-005 as a foliar spray. When applied to targeted weeds, MBI-005 will result in a n ecrosis of actively growing portions resulting in plant death. Proper timing of application to newly emerged weeds is important for optimal results. MBI-005 should be applied to weeds that are 3 inches in height or less. For optimum results, MBI-005 should be applie d to targeted weed species shortly after germination. Thorough coverage of weed folia ge is necessary for effective control.

B. Product Identity/Chemistry

1. Identity of the pesticide and corresponding residues. MBI-005 TGAI consists of the fermentation solids of killed, non-viable Streptomyces acidiscabies strain RL-110 T2

cells. Streptomyces acidiscabies strain RL-110 T selectively targets broadleaf and sedge weeds in cereal grains, corn, sugarcane and tu rf. It is expected when used as proposed

, Streptomyces acidiscabies strain RL-110 T would not result in residues that are of toxicological concern.

2. Magnitude of residues at the time of har vest and method used to determine the

residue. It is expected when used as proposed

, Streptomyces acidiscabies strain RL-110 T

would not result in residues that are of toxicological concern.

3. A statement of why an analytical method of detecting and measuring the levels of the pesticide residue are not needed. An analytical method for residues is not applicable. It is expected when used as proposed, Streptomyces acidiscabies strain RL110 T would not result in residues that are of toxicological concern.

C. Mammalian Toxicological Profile

A variety of toxicity stud ies have been performed with MBI-005. The toxicity studies performed are listed below in Table 1 and include an acute or al toxicity study in rats, an acute dermal toxicity study in rats, an acute inhalation toxic ity study in rats, acute intravenous toxicity studies in rats, acute dermal irritation study in rabbits , an acute eye irritation and toxicity study in rabbits, and a skin sensitiza tion study in guinea pigs. The oral, dermal and inhalation routes of exposur e are the routes relevant for human health risk assessment. When mammals were expos ed through oral and dermal routes, the

results of these studies cons istently showed that MBI-005 was non-toxic and also lacked

irritation as well as sensitiz ation potential. Following inhalation of undiluted MBI-005,

the test substance was rated as moderately toxic in rats, with toxic effects seen at the site of inhalation, the lungs, eff ects that were accompanied by significant decreases in rat body weight at day 14. Given th at human inhalation exposure would not be to undiluted liquid substance, the relevance of these data to risks associated with undiluted MBI-005

is minimal. The results of the intravenous toxicity study showed that MBI-005 containing

S. acidiscabies strain RL-110 T was not pathogenic in mammals. No reports of hypersensitivity have been recorded from pe rsonnel working with this organism. As evidenced by the results of toxicity testi ng summarized below in Table 1, there is no anticipated risk to human health following exposure to MBI-005 through oral, dermal or

inhalation routes.

TABLE 1 Summary of MBI-005 Mammalian Toxicity Data Mammalian Toxicity Test Species Dose Tested Results (Date Completed)

Acute oral toxicity

Kuhn 2009 (OPPTS No. 870.1100) Rat 5000 mg/kg Non-toxic (June 4, 2009)

Acute dermal toxicity

Kuhn 2009a Rat 5050 mg/kg Non-toxic (August 21, 2009)3

(OPPTS No. 870.1200 and OECD 402)

Acute inhalation toxicity

Younger 2009 (OPPTS No. 870.1300 and OECD 403) Rat 2.21 mg/L (undiluted liquid test substance for 4 hours) Moderate toxicity (September 1, 2009)

Acute intravenous toxicity

Monds 2009 (OPPTS No. 885.3200) Rat 9.0 x 10 7 cfu/ml Non-toxic, nonpathogenic (December 29, 2009)

Acute dermal irritation

Kuhn 2009d (OPPTS No. 870.2500 and OECD 404) Rabbit 0.5 ml undiluted product for 4 hours Non-irritating Category IV (July 31, 2009)

Acute eye irritation

Kuhn 2009c (OPPTS No. 870.2400 and OECD 405) Rabbit 0.1 ml undiluted product for 24 hours Minimal irritant Category IV (August 4, 2009)

Skin sensitization

Kuhn 2009e (OPPTS No. 870.2600) Guinea pig 0.4 ml undiluted test substance (given once per week for 3 weeks, followed by a 2 week period before challenge) Not sensitizing (September 18, 2009)

D. Aggregate Exposure

1. Dietary exposure.

i. Food. Dietary exposure from use of MBI-005, as proposed, is minimal. The intended use of the product is to apply MB I-005 as a spray to crops pre-emergent and post-emergent ( i.e., rice, cereal grains, sugarcan e, corn, including field corn, seed corn, popcorn, and corn grown for s eed, and turf, including turf grown for seed) for the control of broadleaf and se dge weeds. Due to the long period of time from application to harvest residues woul d be minimal. Furthermore, the results of toxicity testing following acute oral exposure, the route most relevant to assessment of risks to health from exposur e to food, indicate there is no risk to human health or the environment from MBI-005. There are no reports of ecological or human health hazard s related to oral exposure to Streptomyces sp. or Streptomyces acidiscabies strain RL-110 T . The absence of acute toxicity in laboratory animals following oral exposure to high doses of the product demonstrates the benign nature of MBI-005.

ii. Drinking water. Similarly, exposure of humans to residues of MBI-005 in drinking water would be minimal based on the proposed application rates and

methods. Results of the acu te oral toxicity testing described above have shown4

that MBI-005 was non-toxic at high te st dose (> 5000 mg/kg). There are no reports of ecological or human health hazards related to oral exposure to Streptomyces sp. orStreptomyces acidiscabies strain RL-110 T . The absence of acute toxicity in laboratory animals fo llowing oral exposure to high doses of the product demonstrates the benign nature of MBI-005.

2. Non-dietary exposure . The potential for non-dietar y exposure to the general population, including infants and children, is unlikely as the proposed use sites are application to growing plants or crops. Th e results of toxicity testing discussed

above indicate there is no risk to huma n health or the environment from MBI-005. There are no reports of ecological or human health hazards related to oral

exposure to Streptomyces sp. or Streptomyces acidiscabies strain RL-110 T . The absence of acute toxicity in laboratory animals followi ng oral or dermal exposure to high doses of MBI-005 demonstrates the benign nature of the product. Although some effects were observed in animals exposed through inhalation to high doses of the undiluted MBI-005 product, such exposure would not be seen in the general population as the product is di luted before application. As a result, non-dietary exposures would not be expected to pos e any quantifiable risk.

E. Cumulative Effects

It is not expected that, when used as proposed, MBI-005 would result in residues that are of toxicological concern. The intended use of the product is to apply MBI 005 as

a pre-emergent or post-em ergent spray to crops ( i.e., rice, cereal grains, sugarcane, corn, including field corn, seed corn, popcorn, and co rn grown for seed, and turf, including turf grown for seed) for control of broadleaf a nd sedge weeds. Applic ation of MBI-005 to crops will not result in a substantial increas e in concentration in the environment, in particular since the active i ngredient in MBI-005 is decom posed and detoxified when exposed to biological systems (King et al. 2000. J. Agric. Food Chem. 48:512-514). As indicated in studies by Doumbou et al. (1998; Appl. Environ. Microbiol. 64 :4313-4316) and Lazarovits et al. (2004; Can J. Microbiol. 50 :121-126), thaxtomin A is rapidly degraded by ubiquitous soil organisms such as Ralstonia sp., Penicillium sp., and

Trichoderma sp. More specifically, it was shown that about 75% of thaxtomin A was converted into less phytot oxic thaxtomin transformati on products during a 4-day incubation with a common fungus Aspergillus niger (Lazarovits et al., 2004). The results of toxicity testing indicate th ere is no risk to human health or the environment from MBI005. There are no reports of ecological or human health hazards related to exposure to Streptomyces sp. orStreptomyces acidiscabies strain RL-110 T . The absence of acute toxicity in laboratory animals following exposure to high doses of the product demonstrates the benign nature of MBI-005. The lack of acute toxicity indicates that the

hazard associated with the use of MBI 005 is low.

F. Safety Determination

1. U.S. population. Acute toxicity studies have shown that the MBI-005 is nontoxic in mammals when exposure is through oral or dermal rout es, lacks irritation5

and sensitization potential in mammals , and is only toxic to mammals via inhalation when the exposure is to high doses of undiluted material, an exposure

scenario that is not relevant to the general population. Fu rther, testing in

mammals of active microbes showed that the product was not pathogenic. The intended use of MBI-005 is as a pre-emer gent or post-emergent spray to crops ( i.e., rice, cereal grains, surgarcane, corn, including field corn, seed corn, popcorn, and corn grown for seed, and turf, including turf grown for seed) for control of broadleaf and sedge weeds. The results of toxicity testing indicate there is no risk

to human health or the environment from MBI-005. There are no reports of ecological or human health hazards caused by Streptomyces acidiscabies in general. The lack of acute toxicity indi cates that the hazard associated with the

use of MBI-005 is low. There is a reasona ble certainty of no ha rm to the general United States population from expos ure to this active ingredient.

2. Infants and children . As mentioned above, it is not expected that, when used as proposed, MBI-005 would result in residue s that are of toxi cological concern.

There is a reasonable certain ty of no harm for infants and children from exposure to MBI-005 from the proposed uses.

G. Effects on the Immune and Endocrine Systems

To date there is no evidence to suggest that MBI-005 functions in a manner similar to any known hormone, or ca n act as an endocrine disrupter.

H. Existing Tolerances

There are no current tolerances or tolerance exemptions in place for Streptomyces

acidiscabies strain RL-110 T

I. International Tolerances

There are no current tolerances or tolerance exemptions in place for Streptomyces

acidiscabies strain RL-110 T