**EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE**

**PETITIONS PUBLISHED IN THE FEDERAL REGISTER EPA**  **Registration Division contact:**  **[ P.V 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 -**  **Rem ove” and m**  **aintain the outline. Please do not change the m**  **argins, font, or form at in your pesticide petition. Simply r**  **eplace the instructions that appear in**  **green , i.e., “**  **[ insert com** **pany name ]**  **,” with the inform ation specific to your action.**  **TEMPLATE:** [ **Technology Sciences Group Inc. ]**  **[ IN**  **- 10622**  **]** EPA has received a pesticide petition **( )**  fr om **[ Technology Sciences Group Inc**  **. ]**  **, [**  **1150 18 th**  **Street NW Suite 1000, Washington DC ]**  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. **( Options (pick one)** 

to establish an exemption from the requirement of a tolerance for **coco alkyl dimethyl amines ]**  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 d ata 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 **[ This inform**  **ation is not available, nor required for the establishment of a**  **tolerance exemption. ]**  1. Plant metabolism. **[ NA**  **- Remove**  **]** 2. Analytical method. **[ NA**  **- Remove**  **]** 3. Magnitude of residues. **[ NA** **- Rem**  **ove ]**  B. Toxicological Profile 1. Acute toxicity. [ **The oral LD**  **50 in rats was determ** **ined to be between 1000 and 1300 mg/kg**  **for fem ales.**  **An acute dermal toxicity assay perform ed on the coco alkyl dimethyl amines was**  **reported in rabbits. The LD**  **50 was determ** **ined to be 4.29 mL/kg bw, equivalent to 3385 m g/kg bw.**  **No studies of acute inhalation toxic ity were identified for coco alkyl dimethyl amines. An**  

### LC **50 of**  **>0.6 m g/L was derived in**  **rats for the structurally sim** **ilar hydroxylated am ine**  **. The**  

### LC **50 of >0.6**  **mg/L places this compound into acute inhalation toxicity Category III. C**  **oco alkyl dimethyl am ine**  **s were corrosive to rabbit skin**  **. N,N**  **- dimethyl**  **- 1**  **- hexadecanam** **ine, N,N -**  **dimethyl -**  **1 -**  **tetradecanamine,**2

**and N,N -**  **dimethyl -**  **1 -**  **tetradecanam ine are com** **pounds that constitute coco alkyl dimethyl am ines. All**  **three of these com pounds were irritating to rabbit eyes.**  **]**

**2. Genotoxic**  **i ty.**  **[ Am**  **es assays were reported on three dimethyl alkyl amines that together com** **prise a large percentage of coco alkyl dimethyl amines. There was no evidence of mutagenicity under the conditions of this study for any of the three compounds.** 

**An in vivo**  **ma mmalian erythrocyte m** **icronucleus test of a commercial product containing ~ 70 % C12**  **- , 25 % C12**  **- 14**  **- and 5 % C16**  **- dim**  **ethylalkylamine) was conducted. Significant increases in the percentage of m** **icronucleated polychrom atic erythrocytes in tr**  **eated mice were not found** . ]

3. Reproductive and developmental toxicity. [ **A reproductive/developmental toxicity screening study (OECD TG 421) of N,N**  **- dimethyl**  **- 1**  **- dodecanamine (CAS #112**  **- 18**  **- 5) was conducted in rats.**  **Animals received gavage doses of 0, 50 , 150, 300, or 450 mg/kg bw/day of the test compound for 14**  **days prior to m ating, 14 days during mating, and for females, during pregnancy and lactation. One**  **male and two fem ales from the highest dose group died by day 5 and this group was discontinued. I**  **n the 300 m**  **g/kg bw group, one m ale and six females died and only one pup was born alive. At the 150**  **mg/kg bw dose, two dams died and two dams did not deliver pups. The mean post**  **- implantation loss**  **was significantly higher than the controls (50.4% vs. 13.3%) and the m**  **ean viability index was significantly lower (36.9 % vs. 99.3%).The birth weight of m**  **ale pups was significantly lower than that of controls. Maternal behavior was also affected, as evidenced by an unsevered umbilical cord,**  **cannibalization, and lac k of care of pups. No reproductive or developm**  **ental effects were observed in the absence of m**  **aternal toxicity. The NOAEL for systemic toxicity and for reproductive/developmental toxicity was determ** **ined to be 50 m g/kg bw/day.]** 

4. Subchronic toxicity

. [ **A repeat dose study in rats conducted according to OECD Test Guideline 407 was carried out on N,N**  **- dimethyl**  **- 1**  **- dodecanam** **ine. Animals received gavage doses of 0, 50, 150, or 300 m**  **g/kg bw/day N,N -**  **dim ethyl**  **- 1**  **- dodecanamine for 28 days. At the highest dose, th**  **ree of five fem**  **ales died; nothing significant was observed in the histopathology exam s of these animals.**  **At the m iddle dose, anim**  **als displayed mild adverse behavior, including snout rubbing, but no effects on body weight, food consumption, hematology, clin**  **ical biochemistry, urinalysis or organ weights. A NOAEL of 50 m**  **g/kg/day was determined in this study. ]** 

5. Chronic toxicity. **[ Chronic studies are not available for coco alkyl dimethyl amines**  **]** 6. Animal metabolism. **[ Studies specific to the metabolic**  **pathway or other toxicokinetic properties of coco alkyl dimethyl am** **ines in mammals were not identified in a search of the literature. The prim**  **ary metabolic pathway of coco alkyl dimethyl amines is proposed based on its characteristic molecular structure a**  **nd known m etabolic pathways for structurally similar compounds. In**  **ma mmals, hepatic dealkylation readily occurs with secondary and tertiary am**  **ines with the methyl groups leaving preferentially. Oxidation of the alpha carbon via cytochrom**  **e P450, forms a car**  **binolamine intermediate that will spontaneously cleave to form a secondary am** **ine and carbonyl com** **pound. Subsequent dealkylation of the secondary amine will take place at a slower rate ]**  7. Metabolite toxicology

. **[ No**  **metabolites of toxicological concern have been identified**  **. ]** 3 

### 8. Endocrine disruption

. [ **Toxicity related to endocrine disruption was not observed in the currently available database and the**  **recent OECD 42**  **1 testing.**  ] C. Aggregate Exposure 1. Dietary exposure. **[ C**  **oncentrations will be**  **l ess than 0.5% in food use applications of coco**  **alkyl dimethyl amine. As a result, humans may be exposed to**  **very low residue levels through the**  **diet from** **food and water .**  ] i. Food. **[ Exposure to residues in food are not anticipated to be of toxicologic**  **al concern because**  **the coco alkyl dimethyl am ine**  **biodegrades readily in the environment after application, and is of low general toxicity.**  **Estim ated d**  **ietary exposure was based on the assumption that the inert**  **will be used in all agricultural pesticides a**  **t a proposed limit of**  **0.5 % of the**  **spray volume .**  **The highest exposed subpopulation was children age**  **1 -**  **2 years old, which had an estim ated average**  **exposure of 0. 0186**  **mg /k** **g/day, while the estim ated average exposure of the general population was**  **0.0 0496**  **mg /k** **g /day.**  **Thus, potential dietary exposure will be low and toxicity is generally low, such that a safety finding can be concluded for exposures via the diet.**  **]** ii. Drinking water

. **[ E**  **xposure via drinking water is not expected to be significant. Exposure**  **vi a the drinking water was estim**  **ated assuming a concentration of 100 ppb. This estimated exposure via drinking water did not contribute significantly to the overall dietary exposure.**  **Thus ,**  **potential drinking water exposure will be low, such that a safety f**  **inding for coco alkyl dimethyl am** **ine can be**  **concluded for exposures via the drinking water and the diet com bined.**  **]** 2. Non

- dietary exposure

. **[ Workers may experience dermal exposure during application of**  **pesticide products if personal protective clothing is not worn. Hum**  **ans may also be exposed through the use of**  **non -**  **food use pesticidal products .**  **Concentrations of coco alkyl dimethyl amine are less**  **than 1.0% and derm**  **al exposure will be limited by the irritation potential of the ingredient .**  **Systemic toxicit** **y of coco alkyl dimethyl am ine is low.**  **Thus, a safety finding for coco alkyl dimethyl am** **ine can**  **be concluded for non -**  **dietary exposures .**  ] D. Cumulative Effects **[ T**  **here are no available data or other reliable inform ation that suggests that any toxic**  **effects produced by**  **coco alkyl dimethyl am ine**  **would be cumulative with those o f any other chemical**  **com pounds.**  **Coco alkyl dimethyl m ine**  **does not appear to produce toxic metabolites in common with other substances.**  **It is assumed that**  **coco alkyl dimethyl ami ne**  **does not share a common m echanism**  **of toxicity with other pesticidal**  **substances.** ] E. Safety Determination 1. U.S. population

. **[ T**  **here is a**  **reasonable certainty that no harm to humans will result from**  **the use of coco alkyl dimethyl am** **ine as an inert**  **ing redient in pesticide products.**  **The m ain effect**  **s of**  **oral exposure to coco alkyl dimethyl amine are behavioral**  **effects and developm ental toxicity at**  **maternally toxic dose levels .**  **A NOAEL of**  **50 mg**  **/k g/day**  **following both 28**  **- day repeat dose testing**  **and deve lopmental/reproductive toxicity screening**  **was used to derive the Reference Dose**  **. Intraspecies and interspecies uncertainty factors were combined for a total**  **uncertainty factor of 100 .**  **For the total US population, t he estim**  **ated chronic dietary exposure fro m**  **food and drinking water for**  **coco alkyl dimethyl amine , calculated as**  **0.5 % of all agricultural form**  **ulations, is**  **1.0 % of**  **RfD .**  **]** 2. Infants and children

. **[ A d**  **evelopm ental** **/reproductive toxicity**  **screening stud**  **y n rats**  **dem onstrate**  **s that slight developmenta**  **l effects occurred only at m aternally toxic doses**  **. A**  **n RfD**  **of 0.**  **5 mg/kg/day**  **was derived for coco alkyl dimethyl amine**  **. T**  **he estimated chronic dietary exposure from food and drinking water**  **was highest (**  **3.7 % of**  **RfD ) for children aged 1 to 2 years old.**  ]4

F. I nternational Tolerances **[ NA**  **- Rem**  **ove ]**