


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

EPA Registration Division contact: PV Shah, (703) 308-1846


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.



Stepan Company

[IN-10806]

	EPA has received a pesticide petition (IN-10806) from Stepan Company, 22 West Frontage Road, Northfield, Illinois 60093 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.

	 to establish an exemption from the requirement of a tolerance for

      N,N-dimethyldodecanamide (CAS Reg. No. 3007-53-2) when used as an inert solvent applied to growing crops or harvested crops under 40 CFR 180.910 in pesticide formulations. 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 NA remove

	1. Plant metabolism.

	2. Analytical method. NA remove

	3. Magnitude of residues. NA remove

B. Toxicological Profile Toxicity data were evaluated for the petitioned substance when they were available. When data were not available, toxicity of a commercial mixture of surrogate compounds with structural and metabolic similarity to N,N-dimethyldodecanamide was assessed. The mixture contains 50 - 65% N,N-dimethyloctanamide, 37 - 50% of N,N-dimethyldecanamide, 0 - 5% N,N-dimethylhexanamide, and 0 - 2% N,N-dimethyldodecanamide.

	1. Acute toxicity.  The acute oral LD50 of the mixture of N,N-dimethyloctanamide, N,N-dimethyldecanamide, N,N-dimethylhexanamide, and N,N-dimethyldodecanamide was determined to be 1770 mg/kg body weight.  It was classified as EPA Toxicity Category III for acute oral toxicity. The dermal LD50 of the dimethylalkylamide mixture was determined for male rats to be approximately 2,000 mg/kg and for females, between 400 and 2,000 mg/kg. It was classified as EPA Toxicity Category II for acute dermal toxicity. The acute inhalation LC50 was determined to be >3.55 mg/L in rats exposed in nose/head only chambers. Clinical signs of toxicity were reported for the groups exposed to 0.586 mg/L and higher. The surrogate dimethylalkylamide mixture is classified as EPA Toxicity Category IV for acute inhalation toxicity. The dimethylalkylamide mixture is classified as EPA Toxicity Category I for dermal irritation and ocular irritation and was not sensitizing in guinea pigs according to the Buehler method.


	2. Genotoxicty.  The mixture of N,N-dimethyloctanamide, N,N-dimethyldecanamide, N,N-dimethylhexanamide, and N,N-dimethyldodecanamide produced negative results in a HGPRT assay in Chinese hamster lung cells, in an in vitro chromosome aberration assay in Chinese hamster ovary cells, and in an Ames assay in Salmonella typhimurium tester strains TA1537, TA98, TA100, and TA1535 in the presence and absence of metabolic activation. There is no evidence for genotoxicity of the surrogate mixture or the petitioned substance, N,N-dimethyldodecanamide.

	3. Reproductive and developmental toxicity. Two developmental toxicity studies were carried out on the mixture of N,N-dimethyloctanamide, N,N-dimethyldecanamide, N,N-dimethylhexanamide, and N,N-dimethyldodecanamide: one in the rat and one in the rabbit. Pregnant female rats received gavage doses of 0, 50, 150, or 450 mg/kg bw/day on gestation days 6-15.  On gestation day 21, dams were sacrificed and fetuses were removed by Caesarean section and examined.  Dams in the high dose group exhibited clinical signs of toxicity, a significant decrease in food consumption, and significantly lower body weight gain on days 18 and 19 of gestation.  The corrected weight gain in controls throughout gestation was 7.8%, and in the high dose group the corrected weight gain was 4.9%.   There was also a significant decrease in fetal body weight in the 450 mg/kg group and an increased incidence of fetuses with common skeletal abnormalities and delayed developmental growth.   There were no developmental abnormalities observed in the absence of maternal toxicity. The maternal NOAEL and LOAEL from this study were 150 and 450 mg/kg/day, respectively. The developmental NOAEL and LOAEL were the same as the maternal values. 

In an OECD TG 414 study, rabbits received doses of the dimethylalkylamide mixture on post-coitum days 6-18. Sacrifice took place on day 28 post-coitum. The food consumption of high dose animals was reduced during the dosing period (post coitum days 6-19); this difference was statistically significant during post-coitum days 11-15. There was no significant difference from controls on any reproductive or fetal endpoint for treated fetuses. Study authors concluded that the NOAEL for maternal systemic effects was 300 mg/kg bw based on the decrease in food consumption during dosing. The NOAEL for reproductive and embryotoxicity/teratogenicity was the highest dose of 1000 mg/kg bw.



	4. Subchronic toxicity.  In a 90-day oral study (OECD TG 406), the surrogate substance (the mixture of N,N-dimethyloctanamide, N,N-dimethyldecanamide, N,N-dimethylhexanamide, and N,N-dimethyldodecanamide) was administered in the diet of Wistar rats at 0, 400, 2000, or 10,000 ppm for 13 weeks, and at 0 or 10,000 ppm for 13 weeks followed by a 28-day recovery period. Body weight gain was impaired in females and males at the highest dose, but this did not last into the recovery period.  Increases in liver weights of high dose females were not accompanied by changes in clinical chemistry, gross pathological or histopathology that indicated effects on the function of the liver.  The relative spleen weights among females were significantly higher even after the recovery period. There were no accompanying changes in spleen morphology. High dose males showed an increased incidence of basophilic regenerative tubules in the renal cortex as well as a slight increase in the amount of protein excreted in the urine. These effects were not significant after the recovery period.  The NOAEL in this study was 2000 ppm in males based on reversible kidney effects, and 10,000 ppm in females, equivalent to approximately 136.8 mg/kg bw/day in males and 894.6 mg/kg bw/day in females.


	5. Chronic toxicity. The data available suggest that N,N-dimethyldodecanamide is not carcinogenic.  These include a lack of positive results in all genotoxicity testing in the surrogate chemical mixture of N,N-dimethyloctanamide, N,N-dimethyldecanamide, N,N-dimethylhexanamide, and N,N-dimethyldodecanamide.


	6. Animal metabolism. N,N-dimethyldodecanamide is expected to be metabolized via carboxyamide hydrolysis by amidase enzymes, producing dodecanoic acid, a fatty acid.  Fatty acids are metabolized by beta oxidation in the mitochondria to produce acetyl-CoA, which can enter the citric acid cycle and produce energy.

	7. Metabolite toxicology. N/A Remove
	8. Endocrine disruption. Toxicity related to endocrine disruption was not observed in the currently available N,N-dimethyldodecanamide database, or that of the surrogate chemical mixture of N,N-dimethyloctanamide, N,N-dimethyldecanamide, N,N-dimethylhexanamide, and N,N-dimethyldodecanamide.  As the science develops and resources allow, screening of additional compounds may be added to the Endocrine Disruptor Screening Program (EDSP), at which point N,N-dimethyldodecanamide may be subjected to additional screening and/or testing to better characterize effects related to endocrine disruption.

C. Aggregate Exposure

	1. Dietary exposure. The estimated dietary exposure to N,N-dimethyldodecanamide was determined using methods to estimate chronic dietary exposure for a generic inert ingredient. This assessment considers drinking water and crop-specific residues from pre-harvest applications of agricultural insecticides, herbicides and fungicides, assuming the highest established tolerance level residue for each commodity.  The assessment assumes that the inert ingredient is used on all crops, and that 100% of all crops are treated with the inert.  The inert ingredient is assumed to be present in all commodities treated with 57 of the most significant active ingredients at the maximum tolerance level as identified by the U.S. EPA for the default assessment.  Chronic dietary exposure estimates were derived for the general US population and sub-groups of the population using the Dietary Exposure Evaluation Model, DEEM(TM).  The estimated chronic exposure for the total US population is 0.189 mg/kg/day, 12.6% of the chronic Population Adjusted Dose (cPAD).  Children age 1 to 2 years old have the highest estimated exposure at 0.706 mg/kg/day, or 47.1% of the cPAD.


	i. Food. Dietary exposures of concern are not anticipated for N,N-dimethyldodecanamide due to its ready biodegradation in the environment and low general toxicity.

	ii. Drinking water. N,N-dimethyldodecanamide exposure via drinking water from use as an inert ingredient is not expected to be significant. Based on the physical chemical characteristics, the compound is expected to partition primarily to the soil, and the comparatively small amounts that enter the water will readily biodegrade.  Exposure via the drinking water was estimated in the DEEM dietary exposure assessment assuming a concentration of 100 ppb

	2. Non-dietary exposure. Residential exposures of concern are not anticipated for N,N-dimethyldodecanamide due to its ready biodegradation in the environment and low general toxicity.


D. Cumulative Effects  Section 408(b)(2)(D) (9v) of the 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."  EPA has not made a common mechanism of toxicity finding as to N,N-dimethyldodecanamide and other compounds.  N,N-dimethyldodecanamide does not appear to produce toxic metabolites in common with other substances.  


E. Safety Determination

	1. U.S. population. There is a reasonable certainty that no harm to humans will result from the use of N,N-dimethyldodecanamide as an inert ingredient in pesticide products.  A NOAEL of 150 mg/kg/day in a developmental toxicity study of rats exposed to the mixture of surrogate dimethylalkylamides was used to derive the chronic population adjusted dose (cPAD). Intraspecies and interspecies uncertainty factors were combined for a total uncertainty factor of 100.  The resulting cPAD is 1.5 mg/kg/day.  For the total US population, the estimated chronic dietary exposure from food and drinking water for N,N-dimethyldodecanamide, calculated as 50% of all agricultural formulations, is 12.6 % of cPAD, well below any level of potential concern.    

	2. Infants and children. There is a reasonable certainty that no harm to infants and children will result from the use of N,N-dimethyldodecanamide as an inert ingredient in pesticide products. Mammalian teratology tests in rats and rabbits demonstrate that the chemical mixture of N,N-dimethyloctanamide, N,N-dimethyldecanamide, N,N-dimethylhexanamide, and N,N-dimethyldodecanamide does not cause adverse effects on fetal development in the absence of maternal toxicity.  Thus at this time there is no concern for potential sensitivity to infants and children, and therefore the default 10X FQPA safety factor may be reduced to 1X.  



F. International Tolerances

	N/A Remove




