Document ID: EPA-HQ-OPP-2012-0491-0003
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2012-08-22T04:00Z

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

EPA Registration Division contact: David Lieu (703-305-0079)

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:

Suterra LLC, 20950 NE Talus Place, Bend, Oregon, 97701

2E8043

	EPA has received a pesticide petition (2E8043) from Suterra LLC, 20950 NE Talus Place, Bend, Oregon, 97701 proposing, 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 180.920 to establish an exemption from the requirement of a tolerance for n-heptane (CAS Reg. No. 142-82-5), in or on raw agricultural commodities, when used as an inert ingredient in aerosol, pheromone mating disruption products only, and only in concentrations less than forty percent of the total formulation, and applied to growing crops only.  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.

Suterra, LLC agrees that this summary information pertaining to this petition may be published as a part of the notice of filing of the petition under FFDCA Section 408(d)(3), and as a part of the proposed and/or final regulation issued under FFDCA Section 408. 

   40 CFR 180.7: Petitions Proposing Tolerances or Exemptions for Pesticide 
                Residues in or on Raw Agricultural Commodities
                                       
                Application to Establish an Exemption from the 
                   Requirement of a Tolerance for n-Heptane 
                                       

   A. Residue Chemistry

      1. Plant metabolism.  
      
A complete petition for the proposed establishment of an exemption from the requirement of a tolerance for n-heptane, in or on raw agricultural commodities, when used as an inert ingredient in aerosol, pheromone mating disruption products only, and only in concentrations less than forty percent of the total formulation, and applied to growing crops only is included in this submission.  

Section A(1) of the petition contains confidential information and calculations regarding specific  percentages of inert ingredients contained in an existing, currently registered, aerosol, pheromone mating disruption product for illustration purposes.  Because this specific information about an existing product is confidential, the three confidential pages of Section A(1) have been moved to the Confidential Appendix of this submission.  The location of these three pages can be found at CROSS REFERENCE NO.  1  , page 2 of the Confidential Appendix.

      A.    Residue Chemistry
      
      2.	Analytical method. 
      
      Not applicable.  Suterra LLC is applying for an exemption from the requirement of a tolerance for n-heptane under 40CFR180.910.  Therefore, no analytical method to analyze for n-heptane is enclosed with this petition.

      3. 	Magnitude of residues. 
      
      Based upon the vapor pressure of 46 mm Hg at 25°C, n-heptane is expected to exist entirely in the vapor phase in ambient air (U.S. National Library of Medicine, Hazardous Substances Data Bank, 2012).  Nonvolatile residue of n-heptane is <0.001 g/100ml (CITGO Petroleum Corp, 2007).  Based upon these physical properties, and considering the specific use pattern and limitations under which this exemption from the requirement of a tolerance is being requested (please refer to details of typical application included in Section A(1) of this petition), n-heptane is not expected to accumulate on plant or soil surfaces.  Therefore, no significant amount of n-heptane residue is expected to result from the type of application specified in this petition.
      
B. Toxicological Profile

      1. Acute toxicity. 
      
      Acute Oral
      
      Acute oral LD50 toxicity of n-heptane, via intravenous application to the mouse, has been estimated as 222mg/kg (Jeppsson, Di Paolo). 
      
      Goel et al tested the effect on the liver when rats were injected with n-heptane at 1.0 ml/kg.  The results indicated that enzyme systems in the rat could be caused to malfunction when rats are poisoned by high levels of intraperitoneal injection.
      
      
      Acute Dermal
      
      Direct skin contact with n-heptane may cause pain, burning and itching (Bingham).  Sittig reports that dermal exposure to n-heptane can cause dermatitis and mucous membrane irritation.
      
      Skin contact with liquid n-heptane for one hour led to irritation and dermatitis. (Oettel, 1936, Also cited in the MAK Collection for Occupational Health and Safety)
      
      Jacobs et al tested the limit concentrations of several aliphatic hydrocarbons for skin irritation. Although n-heptane does not appear to have been tested individually, based upon structure-activity relationships and results found for similar substances within the same chemical family, the irritation potential for n-heptane was determined via interpolation.  Test substances were diluted with almond oil at 5, 10, 25, 50 and 100% concentrations by weight.  The highest tested concentration of n-heptane, via interpolation, at which the mean erythema score remained below 2 on the Draize scale was estimated to be 50%.  From this test, a 100% concentration of n-heptane would be estimated to be a skin irritant, based upon results for similar aliphatic hydrocarbons.
      
      Inhalation
      
      Inhalation LC50 toxicity of n-heptane to the rat has been calculated by Babanov as 103,000 mg/m[3]/4-hour. (Also cited by Bingham, Lewis, U.S. National Library of Medicine, ChemIDplus Lite, and Fisher Scientific).  
      
      Bingham also reports that inhalation exposures to 10,000-15,000 ppm n-heptane produced central nervous system depression in mice within 30-60 minutes.  At concentrations higher than 20,000 ppm, exposures caused convulsions and death in mice.  Bingham reports that concentrations of 16,000 ppm are fatal in humans. 
      All of these levels of exposure are at concentration levels that are literally thousands of times greater than would occur via the use of n-heptane via aerosol, pheromone mating disruption products, as illustrated in Section A(1) of this petition.
      
      2. Genotoxicity.
      
      Brooks, et al tested n-heptane, as well as several other solvents for genotoxic effects.  n-Heptane did not induce reverse gene mutation in bacteria, did not cause mitotic gene conversion in yeast, or damage to chromosomes in mammalian cells.
      
      Bingham et al also report that n-heptane was not mutagenic in the Ames Salmonella typhimurium test.
      
      The United States Environmental Protection Agency, Integrated Risk Information System reports that after a comprehensive review of toxicity data associated with n-heptane, this material belongs to Classification D  -  Not classifiable as to human carcinogenicity.
      
      n-Heptane has been shown to be negative in the rat liver chromosome. (Sullivan, Also cited in U.S. National Library of Medicine, Hazardous Substances Data Bank, 2012

      3. Reproductive and developmental toxicity. 
      
      No Information found.

      4. Subchronic toxicity. 
      
      Studies in which rats were exposed to n-heptane for 26 weeks found no evidence of neurological disturbances or organ toxicity.  (Snyder, Bingham)

      5. Chronic toxicity. 
      
      No evidence of chronic toxicity is indicated by Bingham.  The neurotoxicity of n-heptane was studied and compared to the potential neurotoxicity n-pentane and n-hexane by Takeuchi et al.  Wistar strain male rats were exposed to 3000 ppm of n-heptane for 12 hours a day for 16 weeks.  The experiment demonstrated that n-heptane did not disturb the conduction velocity of the motor nerve or prolong the distal latency in the tail of the rat.  The experiment also showed that n-heptane did not impair the peripheral nerve, neuromuscular junction or muscle fiber of rats that were exposed to high levels of n-heptane for 16 straight weeks (Takeuchi). 
      
      Snyder, et al describe an American Petroleum Institute study in which male and female rats were exposed to n-heptane concentrations of 400 and 3,000 ppm for six hours a day / five days a week / for 26 weeks.  No evidence of neurological disturbances or organ toxicity was found.
      
      Populations continuously exposed to the highest levels n-heptane are likely to be oil refinery operators, transport drivers and retail gasoline station attendants (Rappaport).  These personnel are continually exposed to n-heptane (and other saturated hydrocarbons), on a day to day basis, at much higher levels than would be released into the air via aerosol, pheromone mating disruption products as limited by this proposed exemption from the requirement of a tolerance. 
      
      Sullivan and Krieger estimate that n-heptane is present in U.S. finished gasoline at an estimated range of <1 to 5%, with a weighted average of 2%.  Rappaport estimates that oil refinery operators, transport drivers and retail gasoline attendants are continually exposed to air concentrations of n-heptane of 0.243 mg/m[3], 0.275 mg/m[3], and, 0.200 mg/m[3], respectively.  Although these concentrations are difficult to measure and are likely to be highly variable during the course of any given workday, it is interesting to compare these reported levels to the hypothetically calculated maximum, total 24 hour accumulated concentration of 0.0135 mg/m[3] (ppm) that has been calculated to result from the use of n-heptane as proposed in this tolerance exemption petition.  Please recall that the 0.0135 mg/m[3] figure is derived by assuming that all n-heptane released in a 24 hour period accumulates in the airspace of the orchard.  In reality the n-heptane released from an aerosol pheromone mating disruption product immediately flashes off into the atmosphere and out of the treated area, resulting in much lower actual n-heptane concentrations.
      
      
      
      
      
      6. Animal metabolism. 
      
      Based upon the vapor pressure of 46 mm Hg at 25°C, n-heptane is expected to exist entirely in the vapor phase in ambient air. (U.S. National Library of Medicine, Hazardous Substances Data Bank, 2012).  Nonvolatile residue of n-heptane is <0.001 g/100ml. (CITGO Petroleum Corp, 2007).  Based upon these physical properties, and considering the specific use pattern and limitations under which this exemption from the requirement of a tolerance is being requested (please refer to details of typical application included in Section A(1) of this petition), n-heptane is not expected to come into significant contact with non-target animal species.
      
      However, studies have been completed to identify metabolites of n-heptane in the urine of animals that have been exposed to large amounts of this material for several weeks.  Bingham, and also Bahima, indicate that n-heptane is primarily metabolized into its parent alcohols, then those alcohols are conjugated by glucuronates or sulfates and then eliminated in urine.  The primary alcohol metabolites in urine of animals exposed to large amounts of n-heptane via inhalation have been identified as 2-heptanol and 3-heptanol (Bingham and Bahima).  These substances are naturally occurring in many commonly consumed food and drinks, such as banana and coffee, and are currently utilized in the flavoring and fragrance industry (The Good Scents Company)
      
      Soil Degradation by MicroFlora
      
      Garnier et al tested the biodegradation of gasoline and its components when added to a soil consortium.  After 6 days of incubation, 97% of the overall gasoline was biodegraded.  The study also singled out the degradation of n-heptane and several other individual aromatic alkanes.  After 4 days, it was found that 100% of the original concentration of n-heptane was degraded (Garnier).
      
      Another study by Haines et al indicates that n-heptane is fully metabolized by soil microorganisms, as measured by the biological oxygen demand.   Hydrocarbons of lower molecular weight (e.g. n-heptane, a straight chained alkane with seven carbons and a molecular weight of 100.2) were found to be degraded at relatively higher rates than those with higher molecular weights (Haines).  
      
      Solano-Serena also studied the degradation of gasoline and its individual components by microflora from an urban waste water activated sludge.  n-Heptane was found to completely biodegrade after 25 days.  Mineralization into CO2 and microbial cell production were the main products of the carbon in the degraded gasoline.
      
      These studies indicate that even if some small amount of n-heptane did not immediately flash off and were to reach the soil surface and somehow become exposed to soil microorganisms that are present there, the n-heptane would be readily degraded.
      

      7. Metabolite toxicology. 
      
      The primary alcohol metabolites of n-heptane in urine of animals exposed to large amounts of this substance via the inhalation route have been identified as 2-heptanol and 3-heptanol (Bingham).  These substances are naturally occurring in many commonly consumed food and drinks, such as banana and coffee, and are intentionally added to products in the flavoring and fragrance industry (The Good Scents Company)
      
      The toxicity of these alcohols in their concentrated form has been determined.  This information is included herein in the attached Material Safety Data Sheets for these substances (TCI America and Sigma-Aldrich).  These metabolites are not of scientific concern because, as noted in details of the typical application of aerosol pheromone mating disruption products, included in Section A(1) of this petition, the maximum concentration of n-heptane that can be expected to be present in the treated orchard airspace, even if all released n-heptane is conservatively assumed to remain in the airspace for an entire 24 hour period, is estimated at approximately 5.5 x 10-5 mg/L, or 0.0135 ppm.  This figure assumes that all of the released formulation stays within the first 20 vertical feet of the orchard air space for a period of 24 hours.  Of course, in reality, the n-heptane is quickly flashed off and carried out of the treated orchard area by the wind, resulting in much lower expected n-heptane concentrations.  
      
      Perbellini et al report the same major n-heptane biotransformation products from testing completed with rats exposed to 1800 ppm of n-heptane for 6 straight hours.  The data from these tests indicate that one metabolite, 2,5-heptanedione, was detected.  However, because only small amounts of this substance were detected in the urine of animals that were exposed to very high amounts of n-heptane, the authors conclude that this urinary metabolite is highly unlikely to cause clinical damage to the nervous system (Perbellini).  Amounts of n-heptane present in the orchard that would result from the application of aerosol, pheromone mating disruption products are several orders of magnitude lower than 1800 ppm.
      
      Because the level of exposure to n-heptane is expected to be extremely low, the  major metabolites of n-heptane are naturally occurring in many commonly consumed food and drinks, and the major metabolites of n-heptane are readily metabolized, no significant concern for n-heptane metabolites exists.  

	8. Endocrine disruption. No Information found

C. Aggregate Exposure

      1. Dietary exposure.
      
      i. Food.
      
      Based upon the vapor pressure of 46 mm Hg at 25°C, n-heptane is expected to exist entirely in the vapor phase in ambient air (U.S. National Library of Medicine, Hazardous Substances Data Bank, 2012).   Nonvolatile residue of n-heptane is <0.001 g/100ml (CITGO Petroleum Corp, 2007).   Based upon these physical properties, and considering the specific use pattern and limitations under which this exemption from the requirement of a tolerance is being requested (please refer to details of typical application included in Section A(1) of this petition), n-heptane is not expected to accumulate on plant or soil surfaces.  Therefore, dietary exposure via food is not a significant concern.

	ii. Drinking water.

      Based upon the vapor pressure of 46 mm Hg at 25°C, n-heptane is expected to exist entirely in the vapor phase in ambient air (U.S. National Library of Medicine, Hazardous Substances Data Bank, 2012).   Nonvolatile residue of n-heptane is <0.001 g/100ml (CITGO Petroleum Corp, 2007).  Based upon these physical properties, and considering the specific use pattern and limitations under which this exemption from the requirement of a tolerance is being requested (please refer to details of typical application included in Section A(1) of this petition) n-heptane is not expected to accumulate in water.  Therefore, dietary exposure via water is not a significant concern.

	2. Non-dietary exposure.
      
      After release into the airspace of an orchard via an aerosol, pheromone mating disruption product, n-heptane flashes off into the airspace of the orchard.  Based upon the vapor pressure of 45.8 mm Hg at 25°C, n-heptane is expected to exist entirely in the vapor phase in ambient air (U.S. National Library of Medicine, Hazardous Substances Data Bank, 2012).  Nonvolatile residue of n-heptane is <0.001 g/100ml (CITGO Petroleum Corp, 2007).   Due to these physical properties, and considering the specific use pattern and limitations under which this exemption from the requirement of a tolerance is being requested (please refer to details of typical application included in Section A(1) of this petition) n-heptane is not expected to significantly accumulate on the skin or clothing, or in the eyes of applicators/handlers/farm workers or any other surfaces.  Therefore, non-dietary exposure is not expected to be a significant concern.

D. Cumulative Effects

      After release into the airspace of an orchard via an aerosol, pheromone mating disruption product, n-heptane flashes off into the airspace of the orchard.  Based upon the vapor pressure of 46 mm Hg at 25°C, n-heptane is expected to exist entirely in the vapor phase in ambient air (U.S. National Library of Medicine, Hazardous Substances Data Bank, 2012).   Nonvolatile residue of n-heptane is <0.001 g/100ml (CITGO Petroleum Corp, 2007).   Due to these physical properties, and considering the specific use pattern and limitations under which this exemption from the requirement of a tolerance is being requested (please refer to details of typical application included in Section A(1) of this petition) n-heptane, as applied according to the limitations of this petition for the exemption from the requirement of a tolerance, is not expected to be present in quantities large enough to cause cumulative effects to applicators/handlers or any other incidental farm workers.  Therefore, cumulative effects of exposure to n-heptane resulting from the application of aerosol, pheromone mating disruption products, are not a significant concern.

E. Safety Determination

            1.          U.S. population. 
            
      After release into the airspace of an orchard via an aerosol, pheromone mating disruption product, n-heptane flashes off into the airspace of the orchard.  Based upon the vapor pressure of 46 mm Hg at 25°C, n-heptane is expected to exist entirely in the vapor phase in ambient air (U.S. National Library of Medicine, Hazardous Substances Data Bank, 2012).  Nonvolatile residue of n-heptane is <0.001 g/100ml (CITGO Petroleum Corp, 2007).  Due to these physical properties, and considering the specific use pattern and limitations under which this exemption from the requirement of a tolerance is being requested (please refer to details of typical application included in Section A(1) of this petition) n-heptane, as applied according to the limitations of this petition for the exemption from the requirement of a tolerance, is not expected to be present in quantities large enough to expose applicators/handlers or any other incidental farm workers or passersby to significant levels of n-heptane.  
      
      For the same reasons, n-heptane is not expected to accumulate on leaves, fruit, or any other parts of treated orchards.  Residues of n-heptane as applied according to the limitations of this petition for the exemption from the requirement of a tolerance, are not expected to be present in any significant quantity.
      
      Even if any member of the U.S. population were to be exposed to n-heptane via the application of aerosol pheromone mating disruption products, studies have shown (Bingham and Bahima) that n-heptane is metabolized primarily into its parent alcohols (which are normal components of many foods and drinks [The Good Scents Company]) and these metabolites are readily eliminated in urine.  
      
      Therefore, application of n-heptane as present in formulations subject to this proposed exemption from the requirement of a tolerance, within the limitations of this petition, are not expected to cause any significant safety concern to the general U.S. population.

            2.          Infants and children. 
      
      After release into the airspace of an orchard via an aerosol, pheromone mating disruption product, n-heptane flashes off into the airspace of the orchard.  Based upon the vapor pressure of 46 mm Hg at 25°C, n-heptane is expected to exist entirely in the vapor phase in ambient air (U.S. National Library of Medicine, Hazardous Substances Data Bank, 2012).  Nonvolatile residue of n-heptane is <0.001 g/100ml (CITGO Petroleum Corp, 2007).  Due to these physical properties, and considering the specific use pattern and limitations under which this exemption from the requirement of a tolerance is being requested (please refer to details of typical application included in Section A(1) of this petition) n-heptane, as applied according to the limitations of this petition for the exemption from the requirement of a tolerance, is not expected to be present in quantities large enough to expose infants, children, farm workers or any other incidental passersby to significant levels of n-heptane.  
      
      For the same reasons, n-heptane is not expected to accumulate on leaves, fruit, or any other parts of treated orchards.  Residues of n-heptane as applied according to the limitations of this petition for the exemption from the requirement of a tolerance, are not expected to be present in any significant quantity.
      
      Even if any member of the U.S. population were to be exposed to n-heptane via the application of aerosol pheromone mating disruption products, studies have shown (Bingham and Bahima) that n-heptane is metabolized primarily into its parent alcohols (which are normal components of many foods and drinks [The Good Scents Company]) and these metabolites are readily eliminated in urine.  
      
      Therefore, application of n-heptane as present in formulations subject to this proposed exemption from the requirement of a tolerance, within the limitations of this petition, are not expected to cause any significant safety concern to infants and children.

F. International Tolerances

      No specific tolerances have been located for n-heptane as an inert ingredient to be contained in pesticidal formulations.  However, these occupational exposure limits have been defined in the U.S.:
      
      The current Occupational Safety and Health Administration (OSHA) permissible exposure limit (PEL) for n-heptane is 500 ppm. (United States Department of Labor, 2012).
      
      The current National Institute for Occupational Safety and Health (NIOSH) recommended exposure limits (RELs) for n-heptane are: 85 ppm as a time weighted average for up to a 10 hour workday and a 40 hour workweek (United States Department of Labor, 2012).  The NIOSH 15 minute ceiling limit is currently set at 440 ppm (United States Department of Labor, 2012).
      
      Quantitative comparison of any of these current cautionary workplace exposure limits for n-heptane to the hypothetically calculated maximum, total 24 hour accumulated concentration of 0.0135 ppm that would result from a typical aerosol, pheromone mating disruption product (please refer to theoretical calculations in Section A(1) of this petition), quantifies why the application of n-heptane, under the limitations of this proposed exemption from the requirement of a tolerance, presents no significant increase to the risk for unreasonable adverse effects man, non-target species, or the environment.