


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

EPA Registration Division contact: Kerry Leifer; 703-308-8811

INSTRUCTIONS:  Please utilize this outline in preparing the pesticide petition.  In cases where the outline element does not apply, please insert "NA-Remove" and maintain the outline. Please do not change the margins, font, or format in your pesticide petition. Simply replace the instructions that appear in green, i.e., "[insert company name]," with the information specific to your action.

TEMPLATE:

Milliken Chemical

[IN-11359]

	EPA has received a pesticide petition (IN-11359) from Milliken Chemical, 920 Milliken Road Spartanburg, SC 29303, 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 exemption from the requirement of a tolerance for Polymeric Yellow (CAS No. Not Assigned); Poly(oxy-1,2-ethanediyl), alpha, alpha'-{[[4-[(3-sulfophenyl)azo]phenyl]imino]di-2,1-ethanediyl}bis[omega-hydroxy-, monosodium salt] for use as an inert ingredient in pesticide formulations not to exceed 20% wt./wt. under 40 CFR 180.920. EPA has approved Polymeric Yellow for non-food seed treatment colorant use on grass seed.

       EPA has determined that the petition contains data or information regarding the elements set forth in section 408 (d)(2) of FFDCA; 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.

A. Residue Chemistry

	1. Plant metabolism. 	 NA-Remove. No specific plant metabolism data is available, nor is it required for the establishment of a tolerance exemption.

	2. Analytical method. NA-Remove. An analytical method is not required for enforcement purposes since the Agency is establishing an exemption from the requirement of a tolerance without any numerical limitation. 

	3. Magnitude of residues. NA-Remove. Information regarding the nature and magnitude of chemical residues resulting from the use of this inert ingredient is not required for the establishment of a tolerance exemption. 


B. Toxicological Profile

	1. Acute toxicity.  Polymeric Yellow is EPA Toxicity Category III (LD50 >2000 mg/kg) for acute oral toxicity (OECD 420) as rats dosed with undiluted test material at 2000 mg/kg following a range finding study where there was no mortality or clinical signs of toxicity observed. In a primary skin irritation study (OECD 404 B4) on rabbits, no irritation was caused by 4 hours of exposure at 0.5ml of test substance. In a skin sensitization study (OECD 429), a test solution was applied topically on mice concluding the test material was considered to be non-sensitizing.  No relevant data were available on acute inhalation toxicity or eye irritation.

	2. Genotoxicity. Polymeric Yellow did not display mutagenic activity in either revise mutation assays with and without metabolic activation (OECD 471), mouse lymphoma assay with and without metabolic activation (OECD 476), and in vitro micronucleus test with and without metabolic activation (OECD 487).

	3. Reproductive and developmental toxicity. In a Combined Repeated Dose Toxicity Study with a Reproduction/Developmental Toxicity Screening (OECD 422), Polymeric Yellow was administered to 4 groups of 10 males and 10 female rats of the Crl:WI(Han) (Winstar Han IGS) strain for the main study groups and were dosed by oral gavage at dose levels of 0 (vehicle), 100, 300, or 1000 mg/kg/day.  Additionally, 2 groups of 5 males and 5 females were allocated to recovery groups and were dosed by oral gavage at dose levels of 0 (vehicle) or 1000 mg/kg/day.  Based on these, the NOAEL (No Observed Adverse Effect Level) for general toxicity in males and females and for reproductive/developmental toxicity was considered to be 1000 mg/kg mw/day, at the highest dose level used. There were no adverse effects on gonadal function, mating performance, conception, development of the conceptus or parturition. The NOAEL for reproductive performance and fetal developmental toxicity was also considered to be 1000 mg/kg/day.

      There were no test item-related deaths or clinical signs of toxicity.  There were no effects on body weight or food intake for males and females given Polymeric Yellow.  Additionally, there were no changes in behavior or observations in the home cage or open field arena, and no effects on sensorimotor responses.  There were no significant effects on motor activity or grip strength.  

      There were no effects on hematology or blood chemistry parameters on Day 14 of toxicological significance, with the minor statistically significant differences having individual values within the historical Control limits.  Fertility and mating performance were unaffected by Polymeric Yellow administration and there were no effects on pregnancy parameters.  Parturition and pup survival in all groups given the test item were comparable with the concurrent Controls or Historical Control Data ranges and there were no test item-related effects on pup body weights up to Day 13 of age.  There were no effects on the anogenital distance or nipple counts for the F1a animals. 
       
      There were no effects of T4 values in the parental males or Day 13 of age pups.
There were no effects on organ weights for the P generation males and no test item-related macroscopic or microscopic necropsy findings.  There were no external malformations for the F1a animals that were associated with Polymeric Yellow and no changes in thyroid weight of the F1a animals on Day 13 of age.


	4. Subchronic toxicity. The general systemic toxicity NOAEL from the 28-day OECD 422 Combined Repeated Dose Toxicity Study with a Reproduction/Developmental Toxicity Screening Test in Crl:WI(Han) rats was 1000 mg/kg bw/day.

	5. Chronic toxicity. No chronic toxicity data for Polymeric Yellow are available.  In 71 FR 45415, the Agency affirmed the preferred test for repeat dose toxicity is the OECD Test Guideline 422, "Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test".  Milliken Chemical submitted the OECD 422 study for Polymeric Yellow summarizing the results under the Reproductive and Developmental Toxicity section of this document.

	6. Animal metabolism. There are no publicly available mammalian metabolism data reported for Polymeric Yellow, but it is unlikely that metabolism would result in the production of toxic or carcinogenic metabolites based on toxicokinetic data for structurally related pigments.  Additionally, Polymeric Yellow is not mutagenic and not likely to metabolize to any significant degree.
	7. Metabolite toxicology. NA Not required.

	8. Endocrine disruption. Polymeric Yellow does not belong to a class of chemicals known or suspected of having adverse effects on the endocrine system or estrogen receptor.

C. Aggregate Exposure

	1. Dietary exposure. There is no publicly available crop residue information for Polymeric Yellow, but on the basis of the proposed tolerance exemption and the physical/chemical and environmental properties analysis, environmental persistence relating to crop residues are unlikely from the use of Polymeric Yellow as an inert colorant in seed treatment formulations under 40 CFR 180.920 at concentrations not to exceed 20% of the pesticide formulation.  Seed treatment formulas containing Polymeric Yellow will be applied directly to seeds and if released into the environment, the colorant would not be taken up by the germinating seedling and translocated within the plant vascular system to result in crop residues and dietary exposures.

	i. Food. Given low application rates and use pattern, the chronic dietary exposure estimates are well below the level of concern for all U.S. subpopulations.

	ii. Drinking water. Using conservative estimates, exposure to Polymeric Yellow in drinking water based on anticipated concentrations is expected to be negligible. 

	2. Non-dietary exposure. None.

D. Cumulative Effects

	The Agency has not determined that Polymeric Yellow has a common mechanism of toxicity with other substances.

E. Safety Determination

	1. U.S. population. Based on the conservative exposure estimates, there is a reasonable certainty that no harm will result to the U.S. population from aggregate exposure to Polymeric Yellow used at 20% concentration in a pesticide formulation for seed treatment.

	2. Infants and children. The FFDCA Section 408 requires an additional 10x margin of safety for the protection of infants and children in case of threshold effects to account for prenatal and postnatal toxicity, and an inadequate toxicity database.  Where an adequate and reliable database is available and there is a lack of evidence for increased susceptibility, the FQPA safety factor may be reduced or removed.  
      
      Based on available information, Milliken Chemical requests reduction of the FQPA safety factor to 1x and the additional 10x safety factor for the protection of infants and children be removed given favorable toxicity profile, environmental modeling, and physical and chemical characteristics.

F. International Tolerances

	There are no known international tolerances for Polymeric Yellow.




