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-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 

[Joint Inerts Task Force, Cluster Support Team 14]

[Insert Petition Number]

 EPA has received a pesticide petition ([Insert Petition Number]) from [Joint Inerts 

Task Force, Cluster Support Team 14, EPA Company Number 84946], [c/o CropLife 

America, 1156 15th Street, N.W., Suite 400, 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 

amend [the current 40 CFR 180.920 tolerance exemption for the Sodium Salts of N-Alkyl 

(C8 – C18)-β-iminodipropionic Acid (SSNA) inert ingredients to include the exemption from 

the requirement of a tolerance for Sodium and Potassium salts of N-alkyl (C8 – C18)-βiminodipropionic acid under 40 CFR §180.940 uses, including: 

Sodium and potassium salts of N-alkyl (C8 – C18)-β-iminodipropionic acid where the C8 – 

C18 is linear and may be saturated and/or unsaturated provided that the concentration of 

the inert is limited to no more than 30% by weight in pesticide formulations. 

Sodium and Potassium Salts of N-Alkyl (C8 – C18)-β-iminodipropionic Acid 

CAS RN Chemical Name 

110676-19-2 β-alanine, N-(2-carboxyethyl)-N-octadecyl-, dipotassium salt 

3655-00-3 β-alanine, N-(2-carboxyethyl)-N-dodecyl-disodium salt 

61791-56-8 

β-alanine, N-(2-carboxyethyl)-N-tallow alkyl derivs-,disodium 

salts 

14960-06-6 β-alanine, N-(2-carboxyethyl)-N-dodecyl-, monosodium salts 

26256-79-1 β-alanine, N-(2-carboxyethyl)-N-dodecyl-,disodium salt 

90170-43-7 

β-alanine, N-(2-carboxyethyl)-N-coco alkyl derivs-,disodium 

salts 

91696-17-2 

β-alanine, N-(2-carboxyethyl)-N- (C8-C18 and C18 unsat’d 

alkyl) derivs, disodium salt 

97862-48-1 β-alanine, N-(2-carboxyethyl)-N- (C14-C18 and C18 unsat’d 

alkyl) derivs, disodium salt 

 

] 
EPA has determined that the petition contains data or information regarding the elements set 

forth in section 408 (d)(2) of FFDCA; 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

1. Plant metabolism. [Not Applicable] 

 2. Analytical method. [Not Applicable] 

 

 3. Magnitude of residues. [There is no specific crop residue information available for 

Sodium and Potassium Salts of N-Alkyl (C8 – C18)-β-iminodipropionic Acid, and this 

information is typically not available nor required for the establishment of a tolerance 

exemption for inert ingredients.] 

B. Toxicological Profile 

1. Acute toxicity. [The Sodium and Potassium Salts of N-Alkyl (C8 – C18)-βiminodipropionic Acid inerts have low acute oral (EPA Category III or IV) and dermal 

toxicity (EPA Category III), but are potentially corrosive to the skin, and mild to moderate 

eye irritants. The acute oral LD50 of CAS RN 3655-00-3 was found to be greater than 2,000 

mg/kg while LD50 values CAS RN 3546-96-1 are reported to be greater than 5,000 mg/kg in 

rats, 8,000 mg/kg in rabbits, and 17,800 mg/kg in mice. The acute dermal LD50 for CAS RN 

3546-96-1 was greater than 6,800 mg/kg in rabbits. CAS RN 3546-96-1 showed irritating 

properties up to corrosive effects to the rabbit skin in in vivo studies. An in vitro study 

carried out with CAS RN 3655-00-3, demonstrated the potential to be corrosive to the skin 

after a contact period of 24 hours. In vivo studies carried out with mixtures containing CAS 

RN 3546-96-1 showed moderate to mildly irritating properties to the rabbit eye, and 

practically nonirritating effects with rinsing. CAS RN 3655-00-3 was considered to possess 

a weak potential to cause delayed contact hypersensitivity when tested in a guinea pig skin 

maximization test.] 

2. Genotoxicity. [No mutagenicity data were found in the public domain. IARC, 

NTP and OSHA do not list CAS RN 3655-00-3, or any other Sodium and Potassium Salts of 

N-Alkyl (C8 – C18)-β-iminodipropionic Acid, as a carcinogen. Additionally, DEREK SAR 

modeling did not identify any structural alerts for genotoxicity or carcinogenicity.]

3. Reproductive and developmental toxicity. [CAS RN 3655-00-3, β-alanine, N-(2-

carboxyethyl)-N-dodecyl-disodium salt, was tested in an OECD 422 Combined Repeat Dose 

Toxicity Study with the Reproduction/Developmental Toxicity Screening Test. The NOEL 

(No Observed Effect Level) for reproduction and developmental toxicity was established as 

600 mg/kg/day, the highest dose tested. A reproductive/developmental LOAEL was not 

observed.] 

 4. Subchronic toxicity. [Based on the Federal Register Notice (August 9, 2006 Volume 

71, Number 153, pages 45415-45424), the Agency stated that the preferred test for repeat-
dose toxicity is the “Combined Repeated Dose Toxicity Study with the 

Reproduction/Developmental Toxicity Screening Test (OECD Test Guideline 422).” CAS 

RN 3655-00-3, β-alanine, N-(2-carboxyethyl)-N-dodecyl-disodium salt, was tested in the 

OECD 422 Combined Repeat Dose Toxicity Study with a Reproduction /Developmental 

Toxicity Screening Test in rats. 

On the basis of the OECD 422 results, the CAS RN 3655-00-3 maternal and paternal 

parental systemic NOAEL was established at 43mg/kg/day due to the death of one female 

rat after blood sanpling. Parental LOAEL= 160 mg/kg/day based on decreased body weight 

gain in males and females during the pre-mating period and an increased incidence of 

microscopic lesions in the kidney’s of males and acanthosis of the glandular and nonglandular stomachs of females.] 

 

 5. Chronic toxicity. [Based on the Federal Register Notice (August 9, 2006, Volume 

71, Number 153, pages 45415-45424), the Agency stated that the preferred test for repeat 

dose toxicity is the “Combined Repeated Dose Toxicity Study with the 

Reproduction/Developmental Toxicity Screening Test (OECD Test Guideline 422).” 

Therefore, the results of OECD 422 study were submitted and the results are summarized 

under the Reproductive and Developmental Toxicity section of this document.] 

6. Animal metabolism. [There are no published metabolism studies for Sodium and 

Potassium Salts of N-Alkyl (C8 – C18)-β-iminodipropionic Acid surfactants and the 

mammalian metabolism pathway is based on analogy to well-described pathways for 

tertiary amines and fatty acids. Overall it is anticipated that the various metabolites are not 

systemically toxic and would be rapidly conjugated and excreted. The Sodium and 

Potassium Salts of N-Alkyl (C8 – C18)-β-iminodipropionic Acid surfactants (mono and disodium propionates) may be conjugated and excreted directly. The mono and di-potassium 

salts would also be biologically equivalent to the mono and di-sodium salts. Alternatively, 

the tertiary amine dipropionate may be oxidized in the liver by monoamine oxidases to 

generate the intact tertiary amine dipropionate N-oxide which may either be conjugated 

and excreted or metabolically cleaved to a dipropionate oxime type metabolite that is 

conjugated and excreted. The linear fatty acid is metabolized via successive beta-oxidation 

cycles to release acetic acid and eventually carbon dioxide and water.] 

7. Metabolite toxicology. [Based on the proposed Sodium and Potassium Salts of NAlkyl (C8 – C18)-β-iminodipropionic Acid animal metabolic pathway, no metabolites of 

toxicological concern are expected and there is no concern that the postulated animal 

metabolites would have toxicity greater than the parent compounds.] 

8. Endocrine disruption. [The Sodium and Potassium Salts of N-Alkyl (C8 – C18)-βiminodipropionic Acid surfactants do not belong to a class of chemicals known or suspected 

of having adverse effects on estrogen receptors or the endocrine system and have been 

evaluated in acute, repeat dose oral toxicity, developmental and reproductive studies 

capable of detecting effects on endocrine-mediated events. Additionally, the results of these 

studies did not provide any indication of a treatment-related effect on estrogen receptors or 

the endocrine system.] 
C. Aggregate Exposure

1. Dietary exposure. [ EPA assesses potential dietary exposures to inert 

ingredients used in agricultural pesticide formulations using a screening-level model 

referred to as “I-DEEM,” in which the “I” stands for inerts and “DEEM” is the dietary 

exposure evaluation model that is used by EPA to assess dietary exposures to active 

ingredients in pesticide products. EPA’s Inert Ingredients Assessment Branch and residue 

chemists in the Health Effects Division of the Office of Pesticide Programs jointly 

developed I-DEEM. 

The dietary (food plus drinking water) exposures for Sodium and Potassium Salts of NAlkyl (C8 – C18)-β-iminodipropionic Acid 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. 

The dietary exposure assessment for Sodium and Potassium Salts of N-Alkyl (C8 – C18)-βiminodipropionic Acid utilizes the EPA’s dietary screening-level model I-DEEM with 

appropriate adjustments to reflect the use limitations proposed in this petition, i.e., 

concentration is limited to no more than 30% by weight in pesticide formulations. 

 

Based on I-DEEM screening level calculations, with adjustment for use limitations, the 

chronic dietary exposures for SSNA surfactants are estimated to be 0.115748 mg/kg/day 

(27% of the proposed cPAD) and 0.375655 mg/kg/day (87% of the proposed cPAD) for 

children 1-2 years old. 

These estimates demonstrate that the I-DEEM screening-level chronic dietary (food and 

drinking water) exposures are below the cPAD for the general U.S. population and all U.S. 

sub-populations when the proposed formulation concentration limits are accounted for. 

On the basis of the OECD 422 repeat dose toxicity study and comparison of I-DEEM 

exposures to the proposed cPAD, the JITF CST 14 asserts that there is sufficient basis for 

EPA to expand a tolerance exemption for the Sodium and Potassium Salts of N-Alkyl (C8 – 

C18)-β-iminodipropionic acid inert ingredients from 40 CFR 180.920 to include 40 CFR 

Part §180.940 uses. 
Chronic Dietary Safety Assessment, % cPAD 

Study 

Chronic 

Systemic 

NOEL 1

mg/kg 

bw/day 

cPAD 2 

mg/kg 

bw/day 

Percent 

cPAD 

Children 

1-2 years 

of age 

Percent 

cPAD 

U.S. Gen 

Population 

Oral (Gavage) Combined 

Repeated Dose Toxicity 

Study with a 

Reproduction/Developmental 

Toxicity Screening Test of βalanine, N-(2-carboxyethyl)-

N-dodecyl-disodium salt 

(CAS RN 3655-00-3) 

43 0.43 87% 27% 

Note: 

1

 NOEL – No observed effect level 

2

 cPAD – Chronic population adjusted dose, defined as: chronic NOAEL / (safety factors ×

FQPA factor) 

i. Food. [The available data demonstrate that the I-DEEM screening level chronic 

dietary (food and drinking water) exposures are at or below 100% of the cPAD, and have 

been concluded not to be of concern due to the exceptionally conservative nature of the IDEEM assessment.] 

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

Exposure to Sodium and Potassium Salts of N-Alkyl (C8 – C18)-β-iminodipropionic Acid 

inert ingredients from drinking water is expected to be negligible.]

 2. Non-dietary exposure. [The Sodium and Potassium Salts of N-Alkyl (C8 – C18)-βiminodipropionic Acid surfactants are used as inert ingredients in agricultural and 

residential formulations as well as in non-pesticidal formulation uses such as, detergents, 

personal care products, industrial formulations, leather and textile fiber applications, and 

in emulsion polymerization.] 

EPA has conducted screening-level short term and intermediate use residential (nonoccupational) exposure and risk assessments Federal Register (July 29, 2009, Volume 74, 

Number 144, Pages 37584-37591) and has concluded that non-dietary exposure and risk 

are not a concern, (MOE not less than 100). EPA has determined that the combined shortterm aggregated food, water, and residential exposures result in aggregate MOEs of 160 

for both adult males and females and 100 for children. EPA has also determined that the 

combined intermediate-term aggregated food, water, and residential exposures result in 

aggregate MOEs of 430 and 450, for adult males and females, respectively and 110 for 

children. 
EPA as concluded in its Determination of Safety in the Federal Register (July 29, 2009, 

Volume 74, Number 144, Pages 37584-37591): 

“Based on these risk assessments, EPA concludes that there is a reasonable certainty 

that no harm will result to the general population, or to infants and children from 

aggregate exposure to residues of SSNAs.”]

D. Cumulative Effects

[EPA has not conducted a common mechanism evaluation or safety finding for the 

Sodium and Potassium Salts of N-Alkyl (C8 – C18)-β-iminodipropionic Acid surfactants. 

Additionally, as stated in the Federal Register (July 29, 2009, Volume 74, Number 144 Page 

37589): 

“EPA has not found SSNAs to share a common mechanism of toxicity with any 

other substances, and SSNAs do not appear to produce a toxic metabolite produced 

by other substances. For the purposes of this tolerance action, therefore, EPA has 

assumed that SSNAs do not have a common mechanism of toxicity with other 

substances.”] 

E. Safety Determination

1. U.S. population. [In its determination of safety (Federal Register, July 29, 2009, 

Volume 74, Number 144, Pages 37584-37591), EPA concluded that “there is a reasonable 

certainty that no harm will result to the general population, or to infants and children from 

aggregate exposure to residues of SSNAs.”] 

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 and 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 published for the SSNA surfactants (Federal 

Register Notice, July 29, 2009, Volume 74, Number 144, Pages 37584 – 37591), and EPA 

has recommended that the FQPA safety factor be reduced from the default 10x to 1X based 

on the following 

• “The toxicity database for SSNAs is considered adequate for assessing the risks to 

infants and children [...]. 

• No quantitative or qualitative increased susceptibility was demonstrated in the 

offspring in the OPPTS Harmonized Guideline 870.3650 combined repeated dose 

toxicity study with the reproduction/developmental toxicity screening test in rats 

following in utero and post-natal exposure. 

• While there is no chronic toxicity data, the Agency has concluded that an 

additional uncertainty factor is not needed for the use of a subchronic study for a 

chronic exposure assessment based on the minor nature of effects which were seen 
only at the mid- and high-doses as well as the highly conservative nature of the 

exposure assessment. The conservative point of departure selected along with the 

standard uncertainty factor of 100X to account for inter- and intra-species 

variability is considered health protective. 

• There are no neurotoxicity studies available for this series of nonionic surfactants. 

However a Functional Observation Battery (FOB) to evaluate neurotoxicity was 

performed in the Combined Repeated Dose/Developmental Screening study and 

only a minor decrease in temperature was observed in males at the mid and high 

doses. The effect was likely due to normal biological variation and; therefore, was 

not considered treatment-related. Thus, there is no need for a developmental 

neurotoxicity study or additional UFs to account for neurotoxicity. 

• There are no residual uncertainties identified in the exposure databases. The food 

and drinking water assessment is not likely to underestimate exposure to any 

subpopulation, including those comprised of infants and children. The food 

exposure assessments are considered to be highly conservative as they are based 

on the use of the highest tolerance level from the surrogate pesticides for every 

food and 100 PCT is assumed for all crops. EPA also made conservative 

(protective) assumptions in the ground and surface water modeling used to assess 

exposure to SSNAs in drinking water. EPA used similarly conservative 

assumptions to assess post-application exposure of children as well as incidental 

oral exposure of toddlers. These assessments will not underestimate the exposure 

and risks posed by SSNAs.”] 

F. International Tolerances

 [There are no known international tolerances for Sodium and Potassium Salts of NAlkyl (C8 – C18)-β-iminodipropionic Acid pesticide inert ingredients.]