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EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR 

PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER 

EPA Registration Division contact: W. Cutchin, 703-305-7990

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:

Dow AgroSciences, LLC

1E7949

EPA has received a pesticide petition 1E7949 from DowAgroSciences, LLC, 

9330 Zionsville Rd., Indianapolis, IN, 46268 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 a tolerance for N-Alkyl (C8-

C18) Dimethylamidopropylamines (NADMAPA) where the alkyl group is linear and 

may be saturated and/or unsaturated under 40CFR 180.920 when used as an inert 

ingredient in a pesticide formulation with limits of up to 20% of a herbicide formulation. 

NADMAPA is a group of highly related materials that are all derived from the reaction of 

dimethylamidopropylamine (DMAPA) with linear C8-C18 fatty acids. The following 

materials are proposed as being covered by the NADMAPA descriptor:

CAS number PCCode Name

68140-01-2 800287 Amides, coco, N-[3-(dimethylamino)propyl]

146987-98-6 800288 Amides, C8-C18 and C18-unsatd., N-[3-

(dimethylamino)propyl]

1147459-12-8 800289 N-[3-(dimethylamino)propyl]-C12-C18(even numbered)-

alkylamide

3179-80-4 800290 Dodecanamide, N-[3-(dimethylamino)propyl]

45267-19-4 800291 Tetradecanamide, N-[3-(dimethylamino)propyl]

39669-97-1 800292 Hexadecanamide, N-[3-(dimethylamino)propyl]

7651-02-7 800293 Octadecanamide, N-[3-(dimethylamino)propyl]

109-28-4 800294 9-Octadecenamide, N-[3-(dimethylamino)propyl]-,(9Z)-

22890-11-5 800295 Decanamide, N-[3-(dimethylamino)propyl]

22890-10-4 800296 Octanamide, N-[3-(dimethylamino)propyl]
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This petition is based on Coconut fatty acid, dimethylamidopropylamide (Coco 

APDMA; CAS 68140-01-2; Amides, coco, N-[3-(dimethylamino)propyl]) as the 

representative test material for NADMAPA materials. Coco APDMA is a blend and the 

chain length of the R group varies based on the natural origin of the coconut oil. The 

dominant components of the R chain are C12 and C14 at 52.47 and 15.72%, respectively, 

but the chain length ranges from C8 to C18. The petition is made in cooperation with and 

supported in part by proprietary information owned in full or in part by AkzoNobel 

Surface Chemistry LLC. 

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 Specific residue information is not available for NADMAPA, but 

food residues are not expected to be significant. This information is not required for the 

establishment of a tolerance exemption.

1. Plant metabolism. NA-Remove

2. Analytical method. NA-Remove

3. Magnitude of residues. NA-Remove

B. Toxicological Profile The toxicity database for Coco APDMA contains several acute 

toxicity studies: in vitro genotoxicity assays and a repeat dose 

developmental/reproductive screening test (OECD 422). The database is augmented by 

analogue information in the public domain and EPA’s High Production Volume (HPV) 

program. Historically, Coco APDMA is included in subcategory 3 of Category I amides 

within the 2004 HPV summary for Fatty Nitrogen Derived Amides class.

1. Acute toxicity. Coco APDMA has moderate acute oral toxicity with an LD50 of 

300 mg/kg/day and is corrosive and irritating to the skin and eye, respectively.

2. Genotoxicity. Coco APDMA and its broader class of HPV analogues are 

negative for genotoxicity across a series of in vitro assays.

3. Reproductive and developmental toxicity. A combined repeated dose toxicity 

and reproduction and developmental toxicity screening test was conducted in rats with 

Coco APDMA via oral gavage under OECD 422 guidelines and in accordance to Good 

Laboratory Practices (GLP). No treatment-related effects were detected in the 

reproductive or developmental parameters examined. The no observed adverse effect 

level (NOAEL) for repeat dose toxicity was 15 mg/kg/day, and the no observed effect 

level (NOEL) for reproductive and developmental toxicity was the highest dose tested, 45 

mg/kg/day. Coco APDMA is not a reproductive or developmental toxicant.
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4. Subchronic toxicity. A repeat dose NOAEL of 15 mg/kg/day has been 

established for Coco APDMA in an OECD 422 study, but the lowest observed adverse 

effect level (LOAEL) of 45 mg/kg/day was limited to localized gastric irritation due to 

the route of entry (oral gavage) and the corrosive nature of the material, typical of 

surfactants.

5. Chronic toxicity. No chronic studies are available for Coco APDMA, but 

negative findings for genotoxicity and no preneoplastic lesions were observed in the 

OECD 422 study that would suggest potential for carcinogenicity. Neither IARC nor 

other authoritative bodies have classified Coco APDMA or any other NADMAPA 

material as a carcinogen.

6. Animal metabolism. No direct information on animal metabolism is available 

for Coco APDMA. It is generally known that the amide linkage is often preserved in the 

metabolism of amide herbicides and that amines undergo oxidative amine metabolism 

followed by excretion.

7. Metabolite toxicology. Specific information for the metabolites of Coco 

APDMA is not available.

8. Endocrine disruption. The potential for Coco APDMA to interact with the 

endocrine system has not been specifically evaluated in a dedicated study; however, 

based on the available information, there is no indication of a concern for endocrine 

disruption. There was no evidence of treatment-related effects in reproductive or 

developmental parameters in an OECD 422 combined repeated dose toxicity and 

reproduction and developmental toxicity screening test. For analogues, there were no 

adverse effects from pre-natal development (fetal NOAEL-1000 mg/kg/day for coconut 

diethanolamide (CAS 68603-42-9)) nor were adverse effects on reproductive tissues and 

organs reported (dodecanamide,N,N-bis(2-hydroxyethyl)- (CAS 120-40-1); coconut oil 

monoethanolamide (CAS 68140-00-1)).

C. Aggregate Exposure

1. Dietary exposure. The toxicity database supports a proposed endpoint for the 

chronic reference dose (cRfD) and an equivalent chronic population adjusted dose 

(cPAD) of 0.15 mg/kg/day with the reduction of the 10X FQPA Safety Factor (FQPA 

SF) for children to 1X. An acute reference dose (aRfD) is not considered warranted 

based on the corrosivity of the test material that resulted in direct tract/stomach irritation 

(when administered by oral gavage) that would not be relevant to humans.

i. Food. Inert exposure predicted by the EPA Inert Ingredient Assessment 

Branch’s dietary model I-DEEM is used. I-DEEM uses a screening level dietary 

assessment of 57 of the most significant active ingredients as surrogates for inert 

ingredients within the Dietary Exposure Evaluation Model with the Food Commodity 

Intake Database (DEEM-FCIDTM, Version 2.14) software. Exposure from food and 

drinking water are included. The EPA herbicide only I-DEEM food and drinking water 

estimates of exposure are reduced to reflect the 20% formulation limitation and then 
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assessed against the proposed cPAD of 0.15 mg/kg/day.

ii. Drinking water. A conservative default drinking water estimate of 100 ppm is 

included in the I-DEEM model.

2. Non-dietary exposure. No exposure to NADMAPA will occur via residential 

herbicidal products since the proposed pesticide product uses are for crops only. For the 

general population, limited exposure to Coco APDMA may occur through use in 

cosmetics (at very low concentrations), but exposure is not expected for younger 

children. Other non-dietary uses are limited to small percentages, assumed to be 5% or 

less, in the formulations of personal care soaps and shampoos. For the broader 

NADMAPA materials, some exposure to octadecanamide, N-[3-(dimethylamino)propyl]

(CAS 7651-02-7) is possible from high-end hair care dye kits and conditioners, primarily 

for adults. Coconut fatty acid, dimethylamidopropyl analogues have been reviewed by 

the Cosmetic Institute Review and deemed safe when used in rinse-off products and 

known to display low dermal absorption. A dermal absorption estimate of 6% for Coco 

APDMA is supported by a read-across and quantitative structure–activity relationship

(QSAR) analysis within the petition.

D. Cumulative Effects

For the purposes of this tolerance action, it is not assumed that NADMAPA have 

common mechanisms of toxicity with other substances.

E. Safety Determination The results of the exposure assessments coupled with the other 

information in the petition are sufficient to demonstrate that proposed use of NADMAPA 

based on data from Coco APDMA as an inert in herbicide formulations will not result in 

unreasonable adverse effects to humans.

1. U.S. population. Based on the proposed cRfD of 0.15 mg/kg/day and the 20% 

herbicide only formulation limitation, the estimated food and drinking water exposure id 

17% of the cRfD. This result is analogous to a margin of exposure (MOE) of >600, the 

additional margin of safety above 100 is deemed adequate to cover any other potential 

aggregate exposure from non-dietary uses.

2. Infants and children. Reduction of the 10X FQPA SF to 1X is proposed given 

that no reproductive or developmental effects were observed in the OECD 422 study at 

the highest dose tested (NOAEL of 45 mg/kg/day), which is also higher than the 

proposed point of departure at 15 mg/kg/day. This 1X factor is further supported by alkyl 

amides analogue information coupled with limited anticipated exposure from the croponly herbicide use pattern. This information is proposed as adequate for the 

determination of a reasonable certainty of no harm.

Comparison of the predicted exposure from the refined herbicide I-DEEM analysis with 

the NOAEL of 15 mg/kg/day for Coco APDMA results in an estimated exposure for 

children 1-2 yrs old of 53% of the proposed cPAD or an MOE of >190. MOE values for 
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other subpopulations are higher. In general, the Agency is not concerned for MOEs 

greater than 100, when the FQPA SF is reduced to 1X. Because the MOE values from 

the dietary assessment are >180 for children and is considered to be a conservative 

assessment, the additional margin of safety above 100 is deemed adequate to cover any 

other potential aggregate exposure from non-dietary uses. In 2005, the EPA assumption 

for personal care chronic dermal exposure to the analogues of N,N-dimethyloctamide

(CAS 1118-92-9) and N,N-dimethyldecanamide (CAS 14433-76-2) was 0.00032 

mg/kg/day. If a similar level is assumed for NADMAPA and then aggregated with the IDEEM prediction of 0.08 mg/kg/day, the resulting MOE for children remains >190.

F. International Tolerances

There are no known international tolerances for NADMAPA.