Document ID: EPA-HQ-OPP-2021-0612-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2022-06-22T04:00Z

EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER

             EPA Registration Division contact: Kerry Leifer, Branch Chief, Chemistry,  Inerts and Toxicology Assessment Branch (CITAB) 703-308-8811.

             Lamberti-USA, Inc., 161 Washington Street, Conshohocken, PA 19428.

             EPA has received a pesticide petition ([TBD]) from Spring Regulatory Sciences (SRS) on behalf of Lamberti-USA, Inc. (Lamberti), 161 Washington Street, Conshohocken, PA 19428 (EPA Co. No 86861) requesting, pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180 to establish an Inert Ingredient Tolerance Exemption for D-Glucopyranose, oligomeric, maleates, C8-16-branched and linear alkyl glycosides, sulfonated, potassium salts (CAS Nos.  2585031-35-0; 2587364-77-8; 1228577-37-4), hereby referred to as AGEs, K salts under 40 CFR 180.910. EPA has determined that the petition contains data or information regarding the elements set forth in section 408 (d)(2) of  FDDCA; however, EPA has not fully evaluated the sufficiency of the submitted data at this time or whether the data supports granting of the petition. Additional data may be needed before EPA rules on the petition.

             Residue Chemistry
            
             Plant metabolism. Since this request is for an exemption from the Establishment of a Tolerance, no additional residue studies are required.
            
            	2.  Analytical method. An analytical method is not required for enforcement purposes since the Agency has established an exemption from the requirement of a tolerance without any numerical limitation.

             3. Magnitude of residues.  SRS on behalf of Lamberti is petitioning the Agency to add an exemption from the requirement of a tolerance for food use.  Therefore, information regarding the nature and magnitude of chemical residues resulting from the use of this inert ingredient is not required.

             B. Toxicological Profile

             1. Acute toxicity. AGEs have low acute toxicity via the oral route (oral LD50 > 5,000 mg/kg). There is no available data regarding acute exposure via the dermal, eye or inhalation routes.
             
              Genotoxicity. Mutagenicity studies (Ames Test) were available for review for the surrogate chemicals, d- glucopyranose, oligomeric, 6-(dihydrogen 2-hydroxy-1,2,3-propanetricarboxylate), l-(coco alkyl) ethers, sodium salts (CAS No. 151911-51-2), d-glucopyranose, oligomeric, 6-(hydrogen 2- sulfobutanedioate), 1-(coco alkyl) ethers, sodium salts (CAS No. 151911-53-4) or d- glucopyranose, oligomers, monosulfosuccinate, coco alkyl glycosides, sodium salts, d- glucopyranose, oligomeric, 6-[hydrogen (2R,3R)-2,3-dihydroxybutanedioate), 1-( coco alkyl) ethers, sodium salts (CAS No. 151911-52-3). The results of these studies were negative.
              Reproductive and developmental toxicity. In a combined repeated dose toxicity study with the reproduction/developmental toxicity screening test in rats there were no observed adverse effects for parental systemic or reproductive/developmental effects at 1000 mg/kg/day.

             4. 	Subchronic toxicity. NA-Remove
             
             5. Chronic toxicity. 
             A 2 year chronic oral study in rats treated with citric acid was available for review. Rats were administered 5% or 3% citric acid (approx. 2,000 or 1,200 mg/kg/d) in the diet. There were no adverse effects observed at 2,000 mg/kg/day. Chronic studies were also available for the rabbit and dog. There were no adverse effects observed in either study at doses up to 1500 and 1400 mg/kg/day, respectively.
             
              Animal metabolism. Studies on the metabolism of orally administered β-glucosides (metabolic cleavage of alkylglycosides) in mice show that rapid hydrolytic acetal cleavage takes place principally in the stomach and intestine of the mice. The cleavage products pass into the fatty acid and carbohydrate metabolic pathways. That assumption is also confirmed by another study on alkylglycosides where the β-glycosidic bond was rapidly hydrolyzed in intestine and liver. The cleavage products, sugars and long-chain alcohols, entered the pathways of lipid and carbohydrate metabolism.
                     
              Metabolite toxicology. 
                     NA-Remove

              Endocrine disruption. NA-Remove
             C. Aggregate Exposure
             
             In examining aggregate exposure, the Federal Food, Drug, and Cosmetic Act (FFDCA) section 408 directs EPA to consider available information concerning exposures from pesticide residue in food and all other non-occupational exposures, including drinking water from ground water or surface water and exposure through pesticide use in gardens, lawns, or buildings (residential and other indoor uses).
             In addition to pesticide use, the AGEs have reported uses in personal care products, such as antiperspirants, shampoos, conditioners, and moisturizers.
              For the AGEs, a qualitative assessment for all pathways of human exposure (food, drinking water, and residential) is appropriate give the lack of human health concerns associated with exposure to AGEs when used as an inert ingredient in pesticide formulations.
             
             1. Dietary exposure. Dietary exposure to AGEs can occur from eating food treated with AGEs or from drinking water. However, a quantitative assessment was not conducted since an endpoint of concern for risk assessment was not identified.
             
             i. Food. Residues of concern are not anticipated for dietary (food and drinking water) or for residential exposure from the use of AGEs for the proposed use pattern as an inert ingredient in pesticide products. SRS on behalf of Lamberti expects aggregate exposure to the AGEs to pose no appreciable dietary risk, given that the data on the AGEs show a lack of systemic toxicity at doses up to 1000 mg/kg/day.

             ii. Drinking water. Dietary exposure from drinking water to AGEs can occur by drinking water that has been contaminated by run-off from a pesticide treated area. Since an endpoint for risk assessment was not identified, a quantitative dietary exposure assessment from drinking water for AGEs was not conducted.

             2. Non-dietary exposure. The term "residential exposure" is used in this document to refer to non-occupational, non-dietary exposure (e.g., textiles (clothing and diapers), carpets, swimming pools, and hard surface disinfection on walls, floors, tables). AGEs have reported uses in personal care products, such as antiperspirants, shampoos, conditioners, and moisturizers. 180.910. Residential exposure to AGEs is possible; however, since there are no toxicological effects of concern occurring below 1,000 mg/kg bw/day, it is not necessary to conduct assessments of residential (non-occupational) exposures and risks. There are no dermal or inhalation toxicological endpoints of concern to the Agency therefore quantitative assessments have not been conducted.

             D. Cumulative Effects 
             
             		SRS on behalf of Lamberti has not found the AGEs to share a common mechanism of toxicity with any other substances and does not appear to produce a toxic metabolite produced by other substances. For the purposes of this tolerance action, therefore, SRS on behalf of Lamberti has assumed that does not have a common mechanism of toxicity with other substances. For information regarding EPA's efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see EPA's website at http://www.epa.gov/pesticides/cumulative.

             E. Safety Determination

             1. U.S. population. Determination of safety. Based on these risk assessments, SRS on behalf of Lamberti concludes that there is a reasonable certainty that no harm will result to the general population.

             2. Infants and children. SRS on behalf of Lamberti has determined that reliable data shows the safety of infants and children would be adequately protected.

             F. International Tolerances

             SRS on behalf of Lamberti is not aware of any country requiring a tolerance for AGEs, K salts, nor have any CODEX Maximum Residue Levels (MRLs) been established for any food crops at this time.