Document ID: EPA-HQ-OPP-2022-0100-0005
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2022-04-22T04:00Z

OFFICE OF CHEMICAL SAFETY
AND POLLUTION PREVENTION
                 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
                            WASHINGTON, D.C.  20460
              OFFICE OF CHEMICAL SAFETY
AND POLLUTION PREVENTION
                 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
                            WASHINGTON, D.C.  20460

MEMORANDUM

SUBJECT:	Risk Assessment for a New Food Use for LCO SP104 MP, Containing 0.013%      
				Lipo-chitooligosaccharides (LCOs) SP104 as its Active Ingredient.
            
            Action Code Case Number:	00309829
            e-Submission Package ID:	65421		
            EPA EPA Reg No.:                 73314-16; 73314-19
            PC Code: 					006388	
            CAS Number: 				168843-28-5	
            A.I. Tolerance/Exemption: 	40 CFR § 180.1353
            MRID Numbers: 			51626301-08	
            PRIA Code:					B644  
            					

FROM:						
            Risk Assessment Branch
            Biopesticides & Pollution Prevention Division (7511P)

THRU:		
            Risk Assessment Branch
            Biopesticides & Pollution Prevention Division (7511P)

TO:			
            Biochemical Pesticides Branch
            Biopesticides & Pollution Prevention Division (7511P) 

ACTION REQUESTED

On behalf of Monsanto, Exponent requests a new use amendment to add proposed new foliar and in-furrow applications for terrestrial, greenhouse and nursery uses to the labels for the EPA registered end-use product Torque CC[(R)] Seed Treatment (EPA File Symbol: 73314-16), and the EPA registered manufacturing-use product LCO SP104 MP (EPA File Symbol: 73314-19), each containing the active ingredient (AI) lipo-chitooligosaccharides SP104 (SP104). In support of the application for registration, the applicant submitted a proposed product label, data matrices dated 07-09-2021 and product chemistry, human health, and non-target organism data. 

EXECUTIVE SUMMARY

On behalf of Monsanto, Exponent requests a new use amendment to add proposed new foliar and in-furrow applications for terrestrial, greenhouse and nursery uses to the labels for the EPA registered end-use product (EP) Torque CC[(R)] Seed Treatment (EPA Reg. No. 73314-16), and the EPA registered manufacturing-use product LCO SP104 MP (EPA Reg. No. 73314-19), each containing the active ingredient LCO SP104. The EP was originally registered for seed treatment on corn and elicits plant benefits through stimulating the growth of plant roots and promoting microbial symbioses in the root zone.

In support of the new use application the registrant resubmitted human health and non-target organism data and rationale previously reviewed and accepted by the Agency (US EPA 2017a). Genotoxicity data from guideline toxicity studies were also submitted. The Agency has reviewed and evaluated the required data for the proposed new food use. The submitted data and information demonstrate that the active ingredient is of low toxicity and breaks down rapidly in the environment. Furthermore, exposure to the AI is anticipated to be negligible due to its low application rate. Finally, humans are already exposed to lipo-chitooligosaccharides (LCOs) as they are found naturally in foods derived from plants. Although the AI is proposed for a new food-use, the AI is already currently exempt from the requirement of a tolerance in or on all food commodities. Based on the available data and information for the active ingredient, no risks of concern are expected for the proposed new food uses. 

1. Biopesticide Use Pattern

The AI is currently registered for use in Torque[(R)] CC, a liquid formulation used as a seed treatment. The specific LCO in Torque[(R)] CC has dual modes of action that stimulate the growth of plant roots and promotes microbial symbioses in the root zone. Torque[(R)] CC is applied as a water-based slurry directly to the seeds (corn and canola) at a rate of rate of 0.014 ml/kg and 1.2 ml/kg seed (4 x 10[-8] grams AI/A to 1 x 10[-6] grams AI/A) for corn and canola, respectively. The registrant proposes new agricultural uses for the product which include foliar and in-furrow applications for terrestrial, greenhouse, and nursery applications on a broad range of food and non-food crops at a maximal seasonal application rate of 6 x 10[-][5] grams AI/A. For proposed foliar applications, the product is applied via aerial application or ground applications. For ground foliar and in-furrow applications, the product is applied using 1) overhead boom and mist-type systems; 2) sprinklers such as impact, micro-sprinkler, center pivot, lateral move, end tow, side (wheel) roll, traveler, solid set, or hand-move systems; 3) pressurized drench (flood) or drip (trickle) systems; 4) micro-irrigation such as spaghetti tube or individual tube irrigation; 5) hand-held calibrated irrigation equipment such as hand-held wand with injector; and 6) ebb and flow systems. Required personal protective equipment (PPE) include, long-sleeved shirt and long pants, gloves, socks, and shoes. Although the label does not specify if the product is for commercial and/or residential use, based on the PPE requirements, the Risk Assessment Branch (RAB) has assumed it is for commercial use only.

2. Product Chemistry

A. Active Ingredient

All product chemistry data requirements have been satisfied for the sources of the AI. LCO SP104 is from a registered source (EPA File Symbol: 73314-19), so the product chemistry data requirements have already been fulfilled for this active ingredient.

B. End-Use Product

All product chemistry data requirements have been satisfied for the proposed product. Torque[(R)] CC is a registered product (EPA File Symbol: 73314-16), so the product chemistry data requirements have already been fulfilled for this EP. 

3. Human Health Risk Assessment

A. Active Ingredient

Tier I toxicology data (acute testing, subchronic toxicity, developmental toxicity and genotoxicity) are required for technical grade active ingredients (TGAIs). LCO SP104 is from a registered source (EPA File Symbol: 73314-19), so the human health assessment data requirements have been fulfilled for this active ingredient. LCO SP104 is not considered to be acutely toxic based on the available data. The chemical is classified into toxicity category IV for acute oral, dermal and inhalation toxicity and dermal and eye irritation. The substance is not considered to be a dermal sensitizer (US EPA 2017a). 

To satisfy subchronic, developmental, and genotoxicity data requirements for registration of the AI, Monsanto submitted waiver requests (MRIDs 49819918, 51626304, 51626305, 51626306, and 51626308). Part of the waiver rationale discussion, which was reviewed by the Agency, cited toxicity data from eight studies (28-day, 90-day, 1-year, and 2-year oral toxicity) on chemicals with similar molecular structures to LCO SP104. The Agency determined that data from these studies were considered adequate for use in the risk assessment and indicated a lack of adverse effects. For the current new use registration, Monsanto submitted genotoxicity studies. Data from these studies indicate that LCO SP104 is not genotoxic or mutagenic (Table 1). Additionally, studies identified in the literature support a lack of genotoxicity of both LCOs and their metabolites (US EPA 2017a). 

TABLE 1. Genotoxicity Data for LCO SP104 (40 CFR § 158.2050)
                      Data Requirement (OCSPP Guideline)
                                    Results
                                     MRID
Bacterial Reverse Mutation
(870.5100)
Negative for mutagenicity
ACCEPTABLE/GUIDELINE
                                   51626301
In Vitro Mammalian
Chromosome Aberration
(870.5375)
Negative for genotoxicity 
ACCEPTABLE/GUIDELINE
                                   51626302

In addition to the low toxicity of the AI, dietary and occupational exposure to the AI from the proposed new uses is anticipated to be negligible as the proposed application rate is 6 x 10[-5] grams AI/A and LCOs degrade very rapidly due to the presence of plant chitinases. The MP/TGAI is primarily water (99.4%) and it is applied at a low application rate so significant occupational exposure via inhaled vapors is not anticipated. Although dermal/eye exposure could occur, the AI is primarily water and demonstrates low ocular and dermal irritation and toxicity. This information taken together precludes risk for the proposed new use of LCO SP104. 

Lastly, humans are already exposed to LCOs as they are found naturally in plant foods. LCOs are signaling molecules that diffuse into the roots, in addition to being present in bacteria and fungi that are associated with the roots of food crops. Molecules identical to LCO breakdown products are also present in insects, crustaceans, fungi, bacteria and humans, and are regularly consumed as part of a normal diet. Chitin is ubiquitous in the plant and animal kingdoms and is a major component in the integumentary covering structures of arthropods and mollusks and as a component of the cell walls of bacteria. LCO SP104 contains five ß1-4 linked N-acetyl-D-glucosamine (GlcNAc) subunits forming a chitin backbone conjugated with cis-vaccenic acid. Chitosan, a polysaccharide derived from chitin, has numerous food related uses, including use in food preservatives and dietary supplements. Chitosan is also used as a vehicle for orally administered medicines (US EPA 2019). Vaccenic acid is a natural constituent of plant, microorganism, animal and human tissues. Vaccenic acid is readily incorporated into diacylglycerols which are important lipid intermediates and signaling molecules in humans and other living systems. Modified sugars such as GlcNAc are components of glycosaminoglycans, chondroitin, and proteoglycans in the structural matrix of connective tissue in mammals (US EPA 2017a). 

Although the proposed use for the registered active ingredient has not been previously assessed by the Agency, due to a lack of toxicity and low exposure for the product, a qualitative risk assessment is appropriate in lieu of a quantitative assessment for the proposed new use. No risks of concern have been identified.

B. End-Use Product

All acute toxicity data requirements have been satisfied for the proposed product. Torque[(R)] CC is a registered product (EPA File Symbol: 73314-16), so the acute toxicity data requirements have already been fulfilled for this EP. Rationales (MRID 49820004) were provided to bridge the studies submitted by the registrant for the MP to this product. This EP is essentially a water dilution of the MP. Based on data for the MP, the EP is classified into toxicity category IV for acute oral, dermal and inhalation toxicity and dermal and eye irritation. The substance is not considered to be a dermal sensitizer (US EPA 2017b). 

4. Nontarget Organism Risk Assessment

A. Active Ingredient

Tier I nontarget organism toxicity data are required for TGAIs (40 CFR § 158.2060). LCO SP104 is from a registered source (EPA File Symbol: 73314-19), so the non-target organism toxicity data requirements have already been fulfilled for this active ingredient. LCO SP104 is practically nontoxic to birds, fish, aquatic invertebrates, and terrestrial insects. No compound-related phytotoxic effects were observed in non-target plant studies with the AI (US EPA 2017a).  

A quantitative risk assessment was not conducted for nontarget organisms, including endangered/threatened organisms due to the lack of toxicity observed in the available toxicity studies and the unlikelihood of significant nontarget organism exposure based on the natural occurrence, low application rate, and rapid biodegradation of LCO SP104. Risks of concern to nontarget organisms are not anticipated when products are used according to label instructions.  

B. End-Use Product

Nontarget organism data are typically not required for biochemical pesticide EPs, unless triggered based on a concern for toxicity from an inert ingredient. These data requirements have not been triggered at this time for the proposed new use. The BPPD's current risk assessments are sufficient to evaluate the new use. No risks of concern have been identified.

RECOMMENDATIONS AND CONCLUSIONS

1. The label should be updated to accurately reflect the maximum application rate. On page 9 and 20 of the label, the maximum application rate is expressed as "8 oz LCO ai/A per season". This rate is incorrect based on the concentration of the AI in the product and the specified dilution rate. One single application and two seasonal applications of the product would be equivalent to 0.00003 g ai/A and 0.00006 g ai/A, respectively. The rate should be corrected to be expressed as maximum end-use product per acre.     

2. The toxicity data submitted for the EP and TGAI/MP applications are ACCEPTABLE.

3. With regard to the new use pattern, no human health or ecological risks of concern are expected to occur from exposure to the EP and MP/TGAI when label instructions are followed.

BIBLIOGRAPHY OF STUDIES

MRID 51626301: ACCEPTABLE				MRID 51626305: ACCEPTABLE

MRID 51626302: ACCEPTABLE				MRID 51626306: ACCEPTABLE

MRID 51626304: ACCEPTABLE				MRID 51626308: ACCEPTABLE

REFERENCES

US EPA (2017a). Memorandum. Risk Assessment in Support of the Registration of LCO SP104 MP, Containing 0.013% Lipochitooligosaccharide (LCO) SP104 as its Active Ingredient. By Sadaf Shaukat, Biologist. August 1, 2017 

US EPA (2017b). Memorandum. Science Review in Support of the Registration of Torque CC, Containing 0.000001% LCO SP104 as its Active Ingredient. By Sadaf Shaukat, Biologist. August 3, 2017 

US EPA (2019). Science review in support of the addition of Chitosan (Poly-D-Glucosamine) to the list of minimum risk pesticides (MRPs) contained in 40 CFR 152.25(f). By Russell S. Jones, Ph.D., Senior Scientist. August 23, 2019