Document ID: EPA-HQ-OPP-2012-0921-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2013-01-16T05:00Z

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

EPA Registration Division contact: P. V. Shaw, Branch Chief, Inert Ingredient Assessment Branch, 703 308-1846

TEMPLATE:

DuPont Tate & Lyle BioProducts, LLC

2E8091

	EPA has received a pesticide petition (2E8091) from DuPont Tate & Lyle BioProducts, LLC, 198 Blair Bend Drive, Loudon, TN   37774, 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 tolerance for 1,3-propanediol (CAS Reg. No. 504-63-2) under 40 CFR §180.910 for pre- and post-harvest uses in pesticide formulations and 40 CFR §180.940 for food contact sanitizing solutions in public eating places, diary-processing equipment, and food-processing equipment and utensils, when used as an inert ingredient as a solvent, co-solvent, diluent, or freeze point depressant.  1,3-Propanediol would be used in or on the raw agricultural commodity and in the food contact sanitizing solution as an inert ingredient without limitation. 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.

A. Residue Chemistry

	1. Plant metabolism. [NA-Remove] Not required for the establishment of a tolerance exemption for inert ingredients.

	2. Analytical method. [NA-Remove] Not required for the establishment of a tolerance exemption for inert ingredients.

	3. Magnitude of residues. [NA-Remove] Not required for the establishment of a tolerance exemption for inert ingredients.

B. Toxicological Profile

     1. Acute toxicity.  
     1,3-Propanediol has low oral toxicity with a rat LD50 value of greater than 2000 mg/kg, low inhalation toxicity with a rat acute lethal dose greater than the highest dose tested of 1800 mg/m[3], and low dermal toxicity with a rat LD50 of greater than 4200 mg/kg/day.  1,3-Propanediol has low potential for eye irritation based on studies in rabbits. 1,3-Propanediol has low potential for skin irritation and sensitization based on studies in guinea pigs and humans.  
     
     2. Genotoxicity. 
     
     1,3-Propanediol was tested in 4 in vitro genetic toxicity studies involving bacterial and mammalian cells and mutagenicity and clastogenicity endpoints, and in a mouse micronucleus assay by the oral route of exposure.  This substance was not genetically toxic in vitro or in vivo.

     3. Reproductive and developmental toxicity. 
     1,3-Propanediol was not uniquely toxic to the developing fetus at any concentration tested.  No maternal or fetal effects were observed at 1000 mg/kg bw/day, the highest dose tested. 

     The weight of evidence from multiple repeat-dose studies with 1,3-propanediol and reproductive studies with diols that are structurally related, indicate that 1,3-propanediol is unlikely to affect fertility and be reproductively toxic.  There were no pathological or histopathological indicators of reproductive toxicity in the 90-day toxicity study (reproductive organs and sperm parameters) observed following exposure to 1,3-propanediol in Sprague-Dawley rats at doses of 1000 mg/kg/day.  Results for similar diols in rat repeat-dose toxicity rat studies, support the prediction that 1,3-propanediol will not be reproductively toxic.  

     4. Subchronic toxicity. 
     1,3-Propanediol has been evaluated for repeated exposure toxicity in 14-day and 90-day oral toxicity studies in rats, and in a 10-day inhalation toxicity study in rats. The NOEL for 14-day and 90-day repeat-dose oral toxicity is 1000 mg/kg bw/day, the highest dose tested.  The inhalation NOEC is 1800 mg/m[3], the highest dose tested.  This substance has a low potential for repeated exposure toxicity, with no specific target tissues of toxicity identified.

     5. Chronic toxicity. 
     1,3-Propanediol did not produce genetic damage when tested in bacterial and mammalian cells or in laboratory animals, and carcinogenicity via genetic mechanisms is not anticipated.  No tissue damage or systemic effects were observed during repeated inhalation or oral studies at high exposure, and carcinogenicity by epigenetic mechanisms is not predicted.  Carcinogenicity studies for similar diols demonstrated a lack of carcinogenicity, supporting the low potential for carcinogenicity of 1,3-propanediol.

     6. Animal metabolism. 

     Physical-chemical properties help estimate toxicokinetic behavior in mammalian systems.  1,3-Propanediol has a low octanol-water partition coefficient, low vapor pressure, is water soluble, and is readily biodegraded.  These properties are indicators that 1,3-propanediol will be rapidly absorbed by the oral and inhalation routes of exposure and be rapidly metabolized to carbon dioxide and water.  Scientific literature collectively supports a rapid metabolism and transient formation of aldehyde, semi-aldehyde, and acid metabolites.  

     7. Metabolite toxicology. 
     
     The proposed metabolic pathway for 1,3-propanediol follows that for other simple alcohols where alcohol and aldehyde dehydrogenase enzymes sequentially break down this substance to acids used in intermediary metabolism.  Transient metabolites are not expected to be of toxicological concern.

     8. Endocrine disruption. 
     
     This class of chemistry does not belong to a class of chemicals known or suspected of having adverse effects on the endocrine system.
     
C. Aggregate Exposure

The Federal Food, Drug, and Cosmetic Act (FFDCA) section 408 directs EPA to consider available information concerning exposures from the 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).

For 1,3-propanediol, a qualitative assessment for all pathways of human exposure (food, drinking water, and residential) is appropriate given the lack of human health concerns associated with exposure to 1,3-propanediol as an inert ingredient in pesticide formulations and food contact surface sanitizing solutions.

      1.       Dietary exposure. Human exposures to residues of 1,3-propanediol may occur via the dietary (food and drinking water) and/or residential pathways of exposure.  
      
      i.       Food. For the dietary pathway, exposure to residues of 1,3-propanediol would primarily be through the oral route, via consumption of raw agricultural commodities to which pesticide products containing 1,3-propanediol have been applied, food contact with sanitizing solutions on hard surfaces, and/or via consumption of drinking water.  

      ii. 	Drinking water. Based on the environmental fate properties of 1,3-propanediol, it is expected to biodegrade readily and not bioaccumulate in the environment.  It is also soluble, non-volatile, with some mobility.  Exposure to 1,3-propanediol in drinking water is likely to be low.

      2. 	Non-dietary exposure. Exposure may occur via the residential pathway of   exposure (dermal and inhalation routes of exposure), through the use of residential pesticide products containing 1,3-propanediol as an inert ingredient (i.e., insecticides, fungicides, and herbicides), and contact with hard surfaces that contain residual sanitizing solutions.  While dermal exposure may be possible, inhalation exposure is expected to be minimal due to its lack of volatility.

D. Cumulative Effects

	Section 408(b)(D)(v) of FFDCA requires that, when considering whether to establish, modify, or revoke a tolerance, the Agency consider "available information" concerning the cumulative effects of a particular pesticide's residues and "other substances that have a common mechanism of toxicity".

No adverse effects have been demonstrated following exposure to 1,3-propanediol by all routes of exposure, and a common mechanism of toxicity has not been established.  1,3-propanediol has not been shown to produce toxic metabolites.  

E. Safety Determination

	1. U.S. population. 1,3-Propanediol is expected to be safe as used in pesticides and food contact sanitizing solutions as a solvent/cosolvent based on a lack of toxic effects in the studies described above and limited exposure.

	2. Infants and children. 1,3-Propanediol did not exhibit any form of toxicity in repeat-dose studies at limit doses, and there is no reason to believe that infants or children would be more susceptible to the potential effects of 1,3-propanediol.

F. International Tolerances

1,3-Propanediol has a food contact specific migration limit (SML) of 0.5 mg/kg food in Europe, with no further restrictions.

1,3-Propanediol was the subject of a GRAS notification (GRN 302) that identified maximum concentrations for various food categories, and a predicted daily intake of 34 mg/kg bw/day.

1,3-Propanediol is approved as a non-food use inert ingredient in pesticide products at a maximum of 25% by weight in final pesticide formulations.