Document ID: EPA-HQ-OPP-2018-0191-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2022-11-08T05:00Z

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

             EPA Registration Division contact: PV Shah, Branch Chief Inert Assessment Branch (IAB) 703-308-1846.

       Clariant Corporation, 4000 Monroe Rd. Charlotte, NC 28205
       
       
             EPA has received a pesticide petition (IN-11126]) from Spring Trading Company on behalf of Clariant Corporation, 4000 Monroe Rd. Charlotte, NC 28205 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 part180.

  To establish an exemption from the requirement of a tolerance for N,N-dimethylnonanamide (CAS No. 6225-08-7) : under 40 CFR 180.910, 180.920, and 180.930 to include CAS. Reg. No. 6225-08-7. 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.  Clariant believes that the chemistry described by the CAS. Reg. No. 6225-08-7 is described by the published tolerance exemption and therefore would fall under the published tolerance exemption in 40 CFR 180.910, 180.920, and 180.930. Since the current risk assessment was conducted on a range of chemistries to support the published descriptor range of chemistries and EPA has determined that this range of chemistries would be acceptable under this risk assessment Clariant believes this chemistry is supported by the current risk assessment.

 Residue Chemistry

  Since this request is for an exemption from the Establishment of a Tolerance, no additional residue studies are required.
  
  	1.  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.

             2. Magnitude of residues.  Clariant 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. N,N-dimethylnonanamide has a relatively low degree of acute toxicity and is slightly toxic (Toxicity Category III) by the oral, dermal, and inhalation routes of exposure. The acute oral and dermal studies indicate an LD50 of >2000 mg/kg which was the highest dose tested. The acute inhalation LC50 was considered to be >3550.7 mg/m3. An eye irritation test done on the surrogate chemical, N,N-Dimethyldecanamide was found to be an eye irritant within the range of Toxicity category II according to EPA guidance. N,N-dimethylnonanamide is classified as a dermal irritant but is not classified as a skin sensitizer.

              Genotoxicity. N,N-dimethylnonanamide was not mutagenic in the Ames Salmonella assay and did not induce the incidence of chromosomal aberrations with or without metabolic activation in an In Vitro Mammalian Chromosomal Aberration Test. N,N-dimethylnonanamide was also found to be non-mutagenic in an In Vitro Mammalian Gene Mutation Test both in the presence and absence of metabolic activation.
              Reproductive and developmental toxicity. In a Range-finding Study for a Reproduction/Developmental Toxicity Screening on N,N-dimethylnonanamide, no mortality or clinical signs of toxicity were observed.  No treatment-related changes in body weight, feed consumption or absolute and relative organ weights were observed.  The values for the reproductive and developmental parameters examined were similar across groups, including controls.  The NOAEL was 1000 mg/kg/day (the highest dose tested) for systemic, reproductive and developmental toxicity.
             In a prenatal development toxicity study on a mixture of the surrogate chemicals N,N-Dimethyldecanamide and N, N-dimethyloctanamide, dams in the high dose group had severe clinical signs of toxicity, reduced body weight gain and reduced food consumption.  Also at the high dose, a slight increase in post-implantation loss, decreased fetal body weights, an increased incidence of the number of fetuses with "common" abnormal skeletal findings and retardations in skeletal development were seen.  The maternal and developmental toxicity NOAEL was considered to be 150 mg/kg/day based on the above findings.

             4. 	Subchronic toxicity. In a Repeated Dose 28-Day Oral Toxicity in Rodents study N,N-dimethylnonanamide, no mortality occurred during the study.  In addition, no clinical signs of toxicity were observed.  No statistically significant effects were observed on body weight, body weight gain or food consumption in males or on food consumption in females.  In females on day 22 only, body weights were statistically decreased at the mid and high dose.  The effects on body weight were considered incidental since statistical effects were not observed at any other time point in the study.  Percent change in body weight was statistically decreased at all time points reported for high dose females.  The effects on % body weight change at the high dose were considered incidental because they were not accompanied by any effects on food consumption.  Ophthalmoscopic examination revealed no treatment-related effects in the groups examined.  The only finding upon neurological/functional examination of the control and high dose main study animals was a statistically significant decrease in hind limb grip strength in high dose females.  In the absence of any other findings in the neurological/functional examination, this finding was considered incidental.  No effects considered to be treatment-related effects were observed on hematology, clinical chemistry or urinalysis parameters.  Various statistically significant findings were observed on absolute and relative organ weights in males and females.  However, in the absence of any histopathology in these organs or any other related effects, these findings were not considered to be toxicologically significant.  No treatment-related microscopic findings were observed.  The NOAEL was 1000 mg/kg/day, the highest dose tested. 
             
             In a 90-Day Oral Toxicity in Nonrodents study on a mixture of the surrogate chemicals N,N-Dimethyldecanamide and N, N-dimethyloctanamide, uncoordinated movements, nasal discharge, lateral/prone position and trembling as well as mortality (2 deaths) were observed at 1000 mg/kg/day dose.  The deaths of the two dogs could have been due to unintentional intratracheal application of the test material which led to bronchopneumonia in one animals and acute edema in the other animals leading to premature sacrifice or death.  No effects were observed on body weight, body weight gain, food consumption, or ophthalmoscopic examinations.  Microsomal liver enzymes were increased in animals at the high dose (N-demethylase and cytochrome P-450).  Alkaline phosphatase was increased in two animals at the high dose.  No other clinical chemistry, hematology or clinical chemistry parameters were affected by treatment.  No treatment-related gross or microscopic findings were observed.  Absolute and relative liver weights were increased in high dose males.  The NOAEL was considered to be 200 mg/kg/day based on clinical signs of toxicity observed at 1000 mg/kg/day.

             5. Chronic toxicity. No Chronic studies were available on N,N-dimethylnonanamide. The open literature was carefully searched (TOXNET, PubMed, Google Scholar and the internet in general) for any information on the potential carcinogenicity of structurally similar compounds and none was located.   

              Animal metabolism. The mammalian metabolism may be predicted based on either environmental or bacterial degradation or by analogy to documented studies.
                     
              Metabolite toxicology. The animal metabolism of this chemistry has not been investigated and metabolites have not been identified. However, based on the plausible metabolic pathways, no metabolites of toxicological concern are expected.

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

             C. Aggregate Exposure
             
             The Agency's previous assessment for N,N-dimethylnonanamide did not identify any concern for dietary (food and drinking water) or for non-dietary exposure. Clariant believes that the use of the requested CAS. Reg. No. under the current descriptor is not expected to increase the exposure profile.

             1. Dietary exposure. Clariant believes the assumptions used to estimate dietary exposures lead to an extremely conservative assessment of dietary risk due to a series of compounded conservatisms. First, assuming that the level of residue for an inert ingredient is equal to the level of residue for the active ingredient will overstate exposure.

             i. Food. In conducting the acute and chronic dietary exposure assessments, EPA used food consumption information from the United States Department of Agriculture (USDA) 1994-1996 and 1998 Nationwide Continuing Surveys of Food Intake by Individuals (CSFII). As to residue levels in food, no residue data was submitted for N,N-dimethylnonanamide.  In the absence of specific residue data, EPA has developed an approach which uses surrogate information to derive upper bound exposure estimates for the subject inert ingredients. Upper bound exposure estimates are based on the highest tolerance for a given commodity from a list of high-use insecticides, herbicides, and fungicides.

             ii. Drinking water. For the purpose of the screening level dietary risk assessment to support this request for an exemption from the requirement of a tolerance for N,N-dimethylnonanamide, a conservative drinking water concentration value of 100 ppb based on screening level modeling was used to assess the contribution to drinking water for both the acute and chronic dietary risk assessments. These values were directly entered into the dietary exposure model.

             2. Non-dietary exposure. A screening level residential exposure and risk assessment was completed for products containing N,N-dimethylnonanamide as inert ingredients. In this assessment, representative scenarios, based on end-use product application methods and labeled application rates, were selected. For each of the use scenarios, the Agency assessed residential handler (applicator) inhalation and dermal exposure for outdoor scenarios with high exposure potential (i.e., exposure scenarios with high end unit exposure values) to serve as a screening assessment for all potential residential pesticides containing N,N-dimethylnonanamide. Similarly, residential post-application dermal and oral exposure assessments were also performed utilizing high end outdoor exposure scenarios.

             D. Cumulative Effects 
             
             		Clariant has not found N,N-dimethylnonanamide to share a common mechanism of toxicity with any other substances, and N,N-dimethylnonanamide does not appear to produce a toxic metabolite produced by other substances. For the purposes of this tolerance action, therefore, Clariant has assumed that N,N-dimethylnonanamide do not have a common mechanism of   toxicity with other substances.

             E. Safety Determination

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

             2. Infants and children. Clariant has determined that reliable data shows the safety of infants and children would be adequately protected.

             F. International Tolerances

             Clariant is not aware of any country requiring a tolerance for N,N-dimethylnonanamide nor have any CODEX Maximum Residue Levels been established for any food crops at this time.