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EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR 

PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER 

EPA Registration Division contact: [insert name and telephone number with area 

code]

TEMPLATE:

[PP 0E7815]

EPA has received a pesticide petition ([PP 0E7815]) from the Monsanto 

Company, [1300 I Street, NW Suite 450 East Washington, DC 20005] proposing, 

pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 

U.S.C. 346a(d), to establish an exemption from the requirement of a tolerance for [the 

surfactants referred to as Alkyl Amidodimethylpropyl Amines (AADPA) under 40 

CFR §180.910 pre- and post-harvest uses, including;

Chemical Abstract Services Registry Numbers (CAS RNs) supported under the 

following the following tolerance exemption descriptor:

“C3-C12 Alkyl Amidodimethylpropyl Amines (AADPA)”

CAS RN Chemical Name 

1044764-00-2 Amides, C5-C9, N-3-[(dimethylamino)propyl] 

1044754-06-8 Amides C6-C12, N-3-[(dimethylamino)propyl]

MON 51803 is the Monsanto code for the surfactant identified by CAS RN 1044764-

00-2 and the chemical name Amides, C5-C9, N-3-[(dimethylamine)propyl]. MON 

51803 is a representative of the surfactants meeting the description of “C3-C12 

Alkyl Amidodimethylpropyl Amines (AADPA)” and was the test substance used in 

the studies conducted to obtain the data to support this petition.]

A. Residue Chemistry

1. Plant metabolism. [Not applicable or required for the establishment of a 

tolerance exemption for inert ingredients.]

2. Analytical method. [Not applicable or required for the establishment of a 

tolerance exemption for inert ingredients.]
3. Magnitude of residues. [There are no specific crop residue data available 

for AADPA surfactants. This information is not typically required for the 

establishment of a tolerance exemption. The potential residues in or on food or feed 

commodities were assessed based on the EPI SuiteTM 4.0 physicochemical properties 

modeling and environmental fate laboratory data. This information indicated that 

AADPA surfactants are:

Extensively degraded/mineralized through microbial processes.

Rapidly and tightly adsorbed to the soil and should not under desorption. 

Stable to hydrolysis in sterile buffers at pH 4, 7 and 9 at 50o C.

Accordingly, AADPA surfactants should be classified as readily biodegradable and 

not persistent in the environment and are not expected to bioaccumulate. The 

composite of the all available physicochemical properties and environmental fate 

studies provide strong evidence that crop residues would be minimal]

B. Toxicological Profile

1. Acute toxicity. [The AADPA pesticide inert ingredients exhibit EPA 

Category III acute oral toxicity, Category IV acute dermal toxicity, severe eye 

irritation, and moderate skin irritation. The representative test compound, MON 

51803, was slightly toxic to rats after acute oral administration and practically nontoxic after acute dermal administration. MON 51803 was severely irritating to 

rabbit eyes and moderately irritating to rabbit skin, but did not induce dermal 

sensitization in guinea pigs.]

2. Genotoxicity and Mutagenicity. [The representative test compound MON 

51803 demonstrated no evidence of genotoxicity in bacterial mutagenicity assays 

with S. typhimurium and E. coli and no mutagenicity in the in vivo mouse 

micronucleus assay.]

3. Reproductive and developmental toxicity. [MON 51803 was evaluated in the 

Pilot Rat Developmental Toxicity Study (OPPTS 870.3700) and the Combined 90-

Day/One-Generation Rat Reproduction Study (OPPTS 870.3100 and 870.3650). 

The systemic chronic NOAEL, 175 mg/kg/day resulting from the Combined 90-

Day/One-Generation Rat Reproduction Study was chosen as the relevant endpoint 

to evaluate I-DEEM dietary exposure and for FQPA risk assessment. 

The maternal NOAEL in the pilot rat developmental toxicity study was 150 

mg/kg/day due to decreased maternal weight and weight gain as well as food 

consumption in the 500 mg/kg/day test group. There was no effect on fetal growth, 

survival, or morphology in this pilot study. The reproductive toxicity study resulted 

in NOAEL of 175 mg/kg/day for the maternal and pup reproductive and 

developmental endpoints. The reproductive and developmental findings in this 

study were not considered to be of significant concern, or indicative of a specific 

reproductive or developmental toxicant, since they occurred only in the presence of 

severe malnutrition and excessively decreased maternal weight gain. Furthermore, 
no evidence of developmental toxicity was observed in the pilot rat developmental 

toxicity study, even at a dose level (500 mg/kg/day) which caused 25% maternal 

mortality.] 

4. Subchronic toxicity. [The Combined 90-Day/One-Generation Rat 

Reproduction Study (OPPTS 870.3100 and 870.3650) demonstrated maternal 

systemic toxicity at 600 mg/kg/day. The NOAEL was 175 mg/kg/day.]

5. Chronic toxicity. [No chronic toxicity data are available for AADPA 

surfactants.]

6. Animal metabolism. [AADPA metabolism has been postulated based upon 

well-characterized metabolic pathways that have been previously published in texts 

and peer-reviewed journal articles. The initial primary route of metabolism is 

believed to be hydrolysis of the amide bond by amidases to generate the parent C3-

C12 carboxylic acid and dimethylaminopropylamine (DMAPA). 

The mixture of C3-C12 fatty acids should enter the general metabolic pool of 

fatty acids in the body that are obtained primarily from food sources. Fatty 

acids are metabolized primarily by beta-oxidation processes which result in 

successive releases of acetyl CoA (for even carbon chain acids) and propionyl 

CoA (for odd carbon chain acids) which enter into intermediary metabolism 

and/or are metabolized ultimately to carbon dioxide and water.

DMAPA is a dibasic amine and may undergo both primary and tertiary 

amine metabolism. Primary amine metabolism by monoamine oxidases to 

release ammonia would likely be the major route and should predominate 

over alternative oxidative pathways such as N, N-demethylation or N-oxide 

formation. ]

7. Metabolite toxicology. [No metabolites of toxicological concern are expected 

based upon the proposed animal metabolic pathway. EPA has recently reviewed 

and accepted proposed DMAPA mammalian metabolism and granted a tolerance 

exemption for its use as an amine counter ion for the Alkyl (C8-C24) Benzenesulfonic 

Acid Amine Salts (ABAAS) inert ingredients in food use pesticide formulations 

(PP8E7472) that was published as a final rule on August 5, 2009 (Vol. 74, No. 149 

pages 38924-38935).]
8. Endocrine disruption. [The AADPA surfactants do not belong to a class of 

chemicals known or suspected of having adverse effects on the estrogen receptor or 

endocrine system and have been evaluated in acute, repeated oral dose toxicity, 

developmental and reproductive studies capable of detecting effects on endocrine 

mediated events. The representative test compound MON 51803 did not exhibit 

toxicity related to endocrine disruption in the repeated-dose Combined 90-Day/OneGeneration Rat Reproduction Study (OPPTS 870.3100 and 870.3650) and other 

repeated-dose pilot studies, 28- Day Dietary range finding (OPPTS 870.3050) and 

Pilot Rat Developmental Toxicity Study (OPPTS 870.3700).]

C. Aggregate Exposure

1. Dietary exposure. [The dietary (food plus drinking water) exposures for 

AADPA surfactants are expressed as a percentage of the proposed 

chronic population adjusted dose (cPAD) for the general US population 

and children 1-2 years old, the subpopulation with the highest potential 

exposures.

Based on I-DEEM screening level calculations, the chronic dietary 

exposures for the AADPA surfactants are estimated to be 10.9 % of the 

cPAD for the general U.S. population and 35.7% of the cPAD for 

children 1-2 years old.

The toxicological data for the representative test compound MON 51803

do not suggest any qualitative or quantitative evidence or concern for 

increased susceptibility of infants and children from the use of the 

AADPA inert ingredients in pesticide formulations. Therefore, the default 

10X FQPA safety factor may be reduced to 1X, and the cRfD is therefore 

equivalent to the chronic population adjusted dose (cPAD).

CHRONIC DIETARY SAFETY ASSESSMENT, % CPAD

Study

Chronic 

Systemic 

NOAEL 1

mg/kg 

bw/day

cPAD 2

mg/kg 

bw/day

Percent 

cPAD 3

Children 

1-2 years 

of age

Percent 

cPAD 3

U.S. Gen 

Populatio

n

Combined OPPTS 870.3100 

870.3650 90-Day/OneGeneration Rat 

Reproduction Study

175 1.75 35.7% 10.9%

Note:

1 NOAEL – No observed adverse effect level

2 cPAD – Chronic population adjusted dose, defined as: chronic NOAEL 

/ (safety factors FQPA factor)

3 Refer to Petition Appendix IV. Table IV 3.]
i. Food. [The available information demonstrates that the I-DEEM 

screening level chronic dietary (food and drinking water) exposures are well below 

100% of the cPAD, and are therefore below EPA’s established level of concern for 

all U.S. subpopulations.]

ii. Drinking water. [Drinking water is included in the I-DEEM exposure 

assessment. Exposure to AADPA surfactants via drinking water is expected to be 

negligible.]

2. Non-dietary exposure. [The AADPA surfactants will not be formulated for 

use in either non-crop residential pesticide or consumer product formulations. The 

AADPA surfactants supported by way of the Monsanto tolerance exemption petition 

are proposed only for use in pesticide formulation according to 40 CFR § 180.910 

pre- and post-harvest applications.]

D. Cumulative Effects

[For the establishment of the tolerance exemption proposed herein, the 

AADPA surfactants will not have a common mechanism of toxicity with other 

surfactant substances. It is therefore appropriate to consider only the potential risks 

of the compounds included in the exposure assessment provided herein.]

E. Safety Determination

1. U.S. population. [A dietary exposure assessment using current EPA 

inert screening level methodology (I-DEEM) was conducted. Based on the 

conservative I-DEEM dietary exposure estimates, there is a reasonable certainty 

that no harm will result to the US population from the aggregate exposure to 

AADPA surfactants included in to 40 CFR § 180.910 pre- and post-harvest use 

pesticide formulations.]

2. Infants and children. [The FFDCA Section 408 requires an additional 

tenfold margin of safety for the protection of infants and children in case of 

threshold effects to account for prenatal and postnatal toxicity, or an inadequate 

toxicity database. Where an adequate and reliable database is available and there is 

a lack of evidence for increased susceptibility, the FQPA safety factor may be 

reduced or removed. An evaluation of susceptibility and uncertainty issues has been 

performed for the AADPA surfactants. The evaluation, with key points 

summarized below, support that the FQPA safety factor be reduced from the 

default 10X to 1X.

Additionally, under these circumstances the chronic Population Adjusted Dose, 

cPAD, is the same as the Chronic Reference Dose (cRfD) cited above; cPAD = cRfD 

= 1.75 mg/kg/day. 
A scientifically sound mammalian toxicology database, which includes acute, 

repeated-dose oral toxicity, reproductive, and developmental toxicity study data, 

found no adverse effects to sensitive populations.

There was also no consistent evidence of effects on the nervous system in the 

acute, repeated-dose oral toxicity or reproduction study.

The AADPA surfactants do not belong to a class of chemicals known or 

suspected of having adverse effects on the estrogen receptor or endocrine system. 

The Combined OPPTS 870.3100/ 870.3650 90-Day/One-Generation Rat 

Reproduction Study and other repeated-dose testing provided no evidence of 

endocrine disruption.]

F. International Tolerances

[There are currently no international tolerances for the AADPA surfactants 

supported herein.]