2 

EXECUTIVE SUMMARY 

In December 2010 Monsanto submitted a petition to the Environmental Protection Agency, 

herein referred to as the Agency or EPA, to amend 40 CFR 180.910 by establishing an 

exemption from the requirement of a tolerance for the use of amides, C5-C9, N-[3-

(dimethylamino) propyl]; CAS Reg. No. 1044764-00-2 and amides, C6-C12, N-[3-

(dimethylamino) propyl]; CAS Reg. No. 1044764-06-8 as inert ingredients (surfactants) in 

pesticide products applied to growing crops and raw agricultural commodities after harvest. The 

Agency is not aware of any current residential or pesticidal uses for these inert ingredients. For 

ease of reading the aforementioned chemicals will be referred to as alkyl amidodimethylpropyl 

amine (AADPA). 

Acute studies revealed low oral and dermal toxicity, Toxicity Category III and IV, respectively. 

When tested on rabbits, the chemical was shown to be mildly irritating to the skin and severely 

irritating to the eyes, Toxicity Categories IV and I, respectively. Skin sensitization studies in 

guinea pigs showed that the chemical was not a skin sensitizer. 

Several repeat dose studies were conducted on amides, C5-C9, N-[3-(dimethylamino) propyl]. A 

28-day range finding study on rats showed no evidence of toxicity at doses up to 300 mg/kg/day 

(No Observed Adverse Effect Level- (NOAEL)). Systemic toxicity (e.g., lower body weight 

gain, lower food consumption, and effects on red blood cells) were noted at 800 and 1000 

mg/kg/day. Females in the 800 mg/kg/day group also had lower organ weights of the liver, 

spleen, and thymus. 

A second range finding study administered the test substance to female rats on gestation days 6-

19. All females in the 1000 mg/kg/day group were found dead or euthanized in extremis by 

gestation day 8. In the 500 mg/kg/day group, two females were euthanized in extremis. Females 

in this group exhibited clinical signs of toxicity (e.g., rales, increased respiration, gasping, dilated 

pupils, salivation, and body weight gain). There were no test-substance related clinical findings 

noted up to150 mg/kg/day. Intrauterine growth and survival were unaffected at dose levels up to 

500 mg/kg/day. No external malformations or developmental variations were noted in this study. 

The maternal and developmental NOAELs for this study were 150 and 500 mg/kg/day, 

respectively. 

A dietary combined 90-day/Reproductive and Developmental Toxicity Screening Study in rats 

did not show evidence of toxicity at exposures up to 175 mg/kg/day. At the high-dose (600 

mg/kg/day), systemic toxicity was exhibited by clinical findings, lower mean body weights, body 

weight gains, and food consumption for the males, toxicology phase females, and reproductive 

phase females. Lower ovary, uterus, and pituitary weights were noted for the 600 mg/kg/day 

reproductive phase females. In addition, lower litter size, number of pups born, implantation 

sites, and mean pup body weights were noted in the 600 mg/kg/day group in the presence of 

excessive maternal toxicity. Therefore, the systemic, reproductive, and developmental NOAELs 

were considered to be 175 mg/kg/day. This study NOAEL was chosen as the Toxicity Endpoint 

used for all exposure scenarios in this risk assessment. 

An uncertainty factor of 100X was chosen based on 10X interspecies extrapolation and 10X for 

intraspecies variability. No acute endpoint of concern was identified in the available database. 
3 

The EPA has determined that reliable data show the safety of infants and children would be 

adequately protected if the Food Quality Protection Act (FQPA) Safety Factor were reduced to 

1X. Therefore, the chronic Reference dose (cRfD) is equal to chronic Population Adjusted Dose 

(cPAD). 

No carcinogenicity studies are available on AADPAs. The Agency used a qualitative structure 

activity relationship (SAR) database, DEREK Version 11, to determine if there were structural 

alerts suggestive of carcinogenicity. No structural alerts were identified for the parent AADPAs 

nor its major metabolite dimethylaminopropylamine (DMAPA). Based on these results and the 

negative findings in both the mutagenicity and clastogenicity studies along with the lack of 

evidence of specific target organ toxicity, the Agency concluded that these inert ingredients have 

low potential to be carcinogenic. 

Functional observational battery (home cage, handling, open field, neuromuscular, and 

physiological observations) and locomotor activity (no remarkable shifts in the pattern of 

habituation) were recorded for Sprague-Dawley rats treated with 600 mg/kg/day of the test 

substance and no test related effects were observed. 

The proposed initial primary route of metabolism is believed to generate DMAPA. DMAPA has 

been recently evaluated by the Agency and an exemption from tolerance under 40 CFR 180.920 

and 180.930 was established. 

Exposure to AADPAs will be primarily through the oral route of exposure when eating food 

treated with pesticides containing the chemical. Inhalation exposure is not expected based on the 

physical/chemical properties which indicate that volatilization is unlikely. Model estimates for 

oral exposure from the use of these inert ingredients at 50% in formulation (including exposure 

through drinking water) resulted in acceptable dietary exposure to all subpopulations. The most 

highly exposed subpopulation was children 1-2 years old at 35.7% of the cPAD. When 

residential and dietary exposures were combined the exposure did not exceed the acceptable 

level of risk. 

Residential exposure to outdoor pesticide products were evaluated using Agency approved 

models to estimate the risk to residential handlers and post-application exposures. All exposure 

scenarios resulted in acceptable levels of risk to all subpopulations evaluated. Exposure to 

AADPA inert ingredients via paint, residential antimicrobials, pet products, and greenhouses 

were not evaluated in this risk assessment and therefore, should not be permitted in pesticide 

formulations intended for these uses. 

 

Occupational exposure models showed that the use of this inert ingredient will result in 

exposures below the Agency’s level of concern (with the use of gloves in a few occupational 

exposure scenarios). Therefore, the Agency believes there is acceptable risk from the use of 

AADPAs as inert ingredients in pesticide formulations (i.e., herbicides, fungicides, insecticides).

AADPAs are expected to bind to soil and degrade rapidly; therefore, they have a very low 

potential to move to ground or drinking water. Acute ecological toxicity studies revealed that 
4 

AADPA chemicals are slightly toxic to aquatic invertebrates, rainbow trout, and avian species. 

An avian dietary study indicated that AADPAs are practically nontoxic to Northern Bobwhite. 

Based on the findings in this risk assessment the Agency is granting an exemption from the 

requirement of a tolerance under 40 CFR 180.910 for residues of amides, C5-C9, N-[3-

(dimethylamino) propyl]; CAS Reg. No. 1044764-00-2 and amides, C6-C12, N-[3-

(dimethylamino) propyl]; CAS Reg. No. 1044764-06-8 as inert ingredients (surfactants) in 

pesticide products applied to growing crops and raw agricultural commodities after harvest. 
5 

I. BACKGROUND 

In December 2010 Monsanto submitted a petition to the EPA to amend 40 CFR 180.910 by 

establishing an exemption from the requirement of a tolerance for the use of amides, C5-C9, N-

[3-(dimethylamino) propyl]; CAS Reg. No. 1044764-00-2 and amides, C6-C12, N-[3-

(dimethylamino) propyl]; CAS Reg. No. 1044764-06-8 as inert ingredients (surfactants) in 

pesticide products applied to growing crops and raw agricultural commodities after harvest. The 

Agency is not aware of any current residential or agricultural uses for these inert ingredients. 

II. PHYSICAL AND CHEMICAL PROPERTIES

Some of the physical and chemical characteristics of AADPAs are found in Table 1. 

Table 1: Physical and Chemical Properties of AADPA 

Parameter/OPPTS Test 

Guideline Value1 Source 

Generic Structure for 

AADPAs 

 H 

R= C2 – C11 saturated linear 

Petitioner-Monsanto 

CAS Reg. No. 1044764-00-2 and 1044764-06-8 American Chemical 

Society 

Common Names 

Amides, C5-C9, N-[3-

(dimethylamino)propyl]; 

Amides, C6-C12, N-[3-

(dimethylamino)propyl] 

American Chemical 

Society 

Flammability Flame 

Extension 

830.6315 

Did not flash under test conditions MRID 48117101 

Boiling Point (°C) 

830.7220 323 with decomposition MRID 48117101 

pH 

830.7000 10.56 at 24C (1% solution) MRID 48117101 

Vapor Pressure 

830.7950 <0.1 PSI MRID 48117101 

Partition Coefficient 

(Kow)/Log P 

830.7550 

Mean 18.14 measured at 3 different 

ratios of octanol/water 

Log P- 1.26 

MRID 48117101 

Water Solubility 

 830.7840 3.19 g/L at 22C MRID 48117101 

Hydrolysis 

835.2120 

no hydrolysis noted at pH 4, pH 7, or 

pH 9 at 50C MRID 48117103 

Henry's Law Constant 8.85 E-11 EPI Suite 1 Values obtained for CAS Reg. No. 1044764-00-2
6 

III. HAZARD ASSESSMENT

Summary of Toxicity Data: 

Monsanto has submitted studies on amides, C5-C9, N-[3-(dimethylamino) propyl]; CAS Reg. 

No. 1044764-00-2 to represent both chemicals. The C5-C9 carboxylic acid amine content of the 

representative test compound CAS Reg. No. 1044764-00-2 represents 97% of the mass of 

compounds in the alternate C6-C12 carbon chain length (i.e., CAS reg. No. 1044764-06-8). In 

addition, the two AADPA surfactants demonstrate similar physiochemical properties (EPI 

SuiteTM) and metabolic pathways. The Agency agrees that data on amides, C5-C9, N-[3-

(dimethylamino) propyl]; CAS Reg. No. 1044764-00-2 will accurately represent the risk from 

exposure to amides, C6-C12, N-[3-(dimethylamino) propyl]; CAS Reg. No. 1044764-06-8. 

Available toxicity data include an acute toxicity battery (OPPTS Harmonized Test Guidelines 

870.1100, 870.1200, 870.2400, 870.2500, and 870.2600 (acute inhalation study not provided)), a 

90-day Oral Reproductive and Developmental Toxicity Study (OPPTS 870.3650/3100), 2 range 

finding studies (OPPTS 870.3050 and 870.3700), a mutagenicity study (OPPTS 870.5100) and a 

cytogenicity study (OPPTS 870.5395). In addition, sufficient toxicity data are available on the 

metabolite dimethylaminopropylamine (CAS Reg. No. 109-55-7). This includes an acute oral, 

acute inhalation, skin sensitization, subchronic, mutagenicity studies, and an OECD 421 

reproduction/developmental toxicity screening test. (Federal Register, August 5, 2009 (74 FR 

38924, FRL 8430-2)). 

Toxicity Profile: 

Acute Toxicity 

Table 2: Acute Toxicity Profile of AADPA Inerts 

Guideline 

No. Study Type MRIDs # Results

Toxicity 

Category1

870.1100 Acute Oral- Rat 48117110 LD50 3129 mg/kg III 

870.1200 Acute Dermal- Rat 48117111 LD50 >5000 mg/kg IV 

870.2400 Primary Eye 

Irritation- Rabbit 

48117112 Severely irritating I 

870.2500 Primary Skin 

Irritation- Rabbit 

48117113 Mildly irritating IV 

870.2600 Dermal SensitizationGuinea Pig 48117114 Non-sensitizing NA 

1

Toxicity Categories from EPA’s Label Review Manual, Chapter 7, updated August 2007 found at 

http://www.epa.gov/oppfead1/labeling/lrm 
7 

Repeat Dose Toxicity 

A 28-day range finding study (MRID 48117115) was conducted on Sprague-Dawley rats 

administered oral doses of 0, 10/800 (dose was increased to 800 mg/kg on study day 18), 50, 

100, 300 or 1000 mg/kg/day. All rats were observed twice daily for morbidity and mortality and 

once daily for clinical observations. Individual body weights were recorded approximately 

weekly, beginning at least one week prior to test substance administration and ending on the day 

of the scheduled euthanasia. Individual food consumption was recorded weekly, beginning at 

least one week prior to test substance administration. 

Blood samples for clinical pathology (hematology and serum chemistry) and urinalysis 

evaluations were collected from all surviving animals just prior to the scheduled necropsies. 

Gross necropsies were conducted on all surviving animals. Organ weights were taken for the 

following tissues: adrenals, brain, epididymides, heart, kidneys, liver, lung, ovaries with 

oviducts, pituitary, prostate, spleen, testes, thymus and thyroid with parathyroid. Note: uterus 

was not weighed; macroscopic examination only. 

There was no evidence of toxicity noted at exposure levels of 10, 50, 100 or 300 mg/kg/day. 

Systemic toxicity was observed at 800 mg/kg/day (beginning on study day 18) and 1000 

mg/kg/day as evidenced by lower body weight gains and lower food consumption. Decreases in 

liver, spleen and thymus weights (absolute and relative to body and/or brain) were observed in 

the 800 mg/kg/day females. 

A treatment related effect on red blood cells was noted in both the 800 and 1000 mg/kg/day 

groups. In the 800 mg/kg/day group, higher red blood cell count, hemoglobin, and hematocrit 

levels, and lower mean corpuscular volume (MCV) and reticulocyte counts were noted. In the 

1000 mg/kg/day group, lower red blood cell count, hemoglobin, and hematocrit levels, and 

higher reticulocyte counts were noted. The changes in the 800 mg/kg/day group animals were 

considered secondary to dehydration or malnutrition, again correlating with lower food 

consumption noted in this group. The opposite effect on reticulocyte counts and red blood cell 

mass in the 1000 mg/kg/day group animals may be due to an over-compensation for an initial 

reduction in red blood cell counts. Additionally, lower eosinophil levels were noted for the 800 

and 1000 mg/kg/day group animals. 

Based on these finding the no-observed-adverse-effect level (NOAEL) was considered to be 300 

mg/kg/day for males and females. The LOAEL is 800 mg/kg/day based on lower body weight 

gains; lower food consumption; higher red blood cell count, hemoglobin, and hematocrit levels; 

and lower MCV and reticulocyte counts in both sexes. 

Developmental and Reproductive Toxicity

Study 1 

An oral (gavage) range-finding prenatal developmental toxicity study was conducted on 

Sprague-Dawley rats (MRID 48117117). Female rats were given 0, 15, 50, 150, 500, or 1000 

mg/kg/day on gestation days (GD) 6 through 19. 
8 

All animals were observed twice daily for mortality and morbidity. Individual clinical 

observations were recorded from GD 0 to 20. Body weights and food consumption were 

recorded on GD 0 and 6-20 (daily). On GD 20 a laparohysterectomy was performed on each 

surviving female. The uteri, placenta, and ovaries were examined, and the numbers of fetuses, 

early and late resorptions, total implantations, and corpora lutea were recorded. Gravid uterine 

weights were recorded, and net body weights and net body weight changes were calculated. The 

fetuses were weighed, sexed, and examined for external malformations and developmental 

variations. 

All eight females in the 1000 mg/kg/day group were found dead or euthanized in extremis by 

gestation day 8. These females were noted with rales, hypoactivity, prostration, clonic 

convulsions, gasping, shallow respiration, red and/or clear material around nose and/or mouth, 

and dilated pupils at the daily examination or approximately 1 hour following dose 

administration 1 day prior to or on the day of death or euthanasia. Additionally, body weight 

losses and reduced food consumption prior to death or euthanasia were noted for these females. 

The mortality at 1000 mg/kg/day precluded the evaluation of laprohysterectomy parameters and 

fetal morphology at this dose level. 

In the 500 mg/kg/day group, two females were euthanized in extremis on gestation day 9 or 14. 

Females in these groups, including the two females that were euthanized in extremis, were noted 

with rales, increased respiration, dilated pupils, gasping, decreased defecation, labored 

respiration, salivation, and/or clear and/or red material around the nose, mouth, and/or forelimbs 

at the daily examinations or approximately 1 hour following dose administration. Additionally, 

reductions in mean maternal body weights, body weight gains, and food consumption were noted 

in the 500 mg/kg/day group throughout the entire treatment period (GD 6-20). There were no 

test-substance related clinical findings noted in the 15, 50, and 150 mg/kg/day groups. 

At necropsy, two females in the 1000 mg/kg/day group and one females in the 500 mg/kg/day 

group were noted with a distended stomach, and/or gas-filled distended stomach, duodenum, 

jejunum, ileum, cecum, and colon. One female in the 500 mg/kg/day group (euthanized in 

extremis on GD 14) was noted with thick brown contents in the vagina. Intrauterine growth and 

survival were unaffected at dose levels of 15, 50, 150, and 500 mg/kg/day. No external 

malformations or developmental variations were noted in this study. 

The Agency has determined that the maternal NOAEL is 150 mg/kg/day and the LOAEL is 500 

mg/kg/day based on decreased in body weight gain, lower food consumption and mortality 

The developmental NOAEL is 500 mg/kg/day, while the developmental LOAEL was not 

established. 

Study 2 

A dietary 90-day one generation Reproductive and Developmental Toxicity Screening Study 

(MRID 48117116; OPPTS 870.3100 and 870.3650) in Sprague-Dawley rats was conducted at 

dose levels of 0, 15, 50, 175, and 600 mg/kg/day. 

All animals were observed twice daily for mortality and morbidity, and clinical observations 

were performed once daily. Physical examinations, body weights, and food consumption were 
9 

recorded at least weekly for the males, toxicology phase females, and during the pre-mating 

period for the reproductive phase females. The reproductive phase female body weights were 

recorded on gestation days 0, 4, 7, 11, 14, 17, and 20 and on lactation days 1, 4, 7, 14, and 21. 

Food consumption was measured on gestation days 0-20 (daily) and lactation days 1-21 (daily) 

for the reproductive phase females. 

Functional observational battery (FOB) and locomotor activity were recorded for males and 

toxicology phase females during the last week of test diet exposure. Hematology, serum 

chemistry, and urinalysis parameters were evaluated for the males and toxicology phase females 

on the day of euthanasia. The study also looked at the effects on reproductive and developmental 

performance including gonadal function, estrous cyclicity, mating behavior, conception, 

gestation, parturition, lactation, and on growth and development of the offspring. F1 pups were 

necropsied on postnatal day (PND) 21. 

No evidence of toxicity was noted at exposure levels of 15, 50, and 175 mg/kg/day. At the highdose (600 mg/kg/day), systemic toxicity was exhibited by clinical findings, lower mean body 

weights, body weight gains, and lower food consumption for the males, toxicology phase 

females and reproductive phase females. Test substance-related clinical findings observed in the 

600 mg/kg/day group reproductive phase females included red material around the nose observed 

predominantly during the gestation and/or lactation periods and yellow material around the 

urogenital area which was occasionally noted during exposure for the 600 mg/kg/day males and 

reproductive phase females. Lower absolute and relative-to-brain ovary, uterus, and pituitary 

weights were noted for the 600 mg/kg/day reproductive phase females. In addition, lower litter 

size, number of pups born, implantation sites, and mean pup body weights were noted in the 600 

mg/kg/day group in the presence of excessive maternal toxicity. 

The parental systemic NOAEL is 175 mg/kg/day and the LOAEL is 600 mg/kg/day based on 

lower mean body weights, body weight gains, and food consumption for both sexes and lower 

absolute and relative-to-brain ovary, uterus, and pituitary weights for the reproductive phase 

females. 

The reproductive/developmental NOAEL is 175 mg/kg/day and the LOAEL is 600 mg/kg/day, 

based on lower mean live litter size on PND 0, number of pups born and implantation sites, and 

lower mean pup weights. All reproductive and developmental effects were noted in the presence 

of maternal toxicity. 

Neurotoxicity

A specific neurotoxicity study was not conducted on the supported chemicals. However, 

functional observational battery (home cage, handling, open field, neuromuscular, and 

physiological observations) and locomotor activity (no remarkable shifts in the pattern of 

habituation) were recorded for Sprague-Dawley rats treated with 600 mg/kg/day of the test 

substance and no test related effects were observed. (MRID 48117116) Although evidence of 

neurotoxicity was observed in the range-finding prenatal developmental toxicity study (MRID 

48117117), as indicated in the 500 mg/kg/day group (dilated pupils) and the 1000 mg/kg/day 

group (dilated pupils and clonic convulsions), these clinical signs were considered to be due to 
10 

generalized toxicity and not of neurologic origin. The Point of Departure (POD) of 175 

mg/kg/day used in this risk assessment is protective of the effects seen at these dose levels. 

Mutagenicity

Amides, C5-C9, N-[3-(dimethylamino) propyl] was evaluated in an Ames Assay (MRID 

48117118) for their ability to induce reverse mutations at the histidine locus in multiple strains of 

Salmonella typhimurium (TA98, TA100, TA1535, and TA1537); and at the tryptophan locus of 

Escherichia coli (E. coli) strain WP2uvrA in the presence or absence of an exogenous 

mammalian metabolic activation system (S9). Amides, C5-C9, N-[3-(dimethylamino) propyl] 

was evaluated in the initial mutagenicity assay, in all five tester strains, at doses of 0, 1.6, 5, 16, 

50, 160, 500, 1600, or 5000 μg/plate with and without S9. No positive increases were observed 

with any of the tester strains in the presence or absence of S9 mix. 

Based on the results of the initial assay, amides, C5-C9, N-[3-(dimethylamino) propyl] was reevaluated in the confirmatory mutagenicity assay at doses of 0, 33.3, 100, 333, 1000, 2000, or 

5000 μg/plate with and without S9. No positive increases were observed with any of the tester 

strains in the presence or absence of S9 mix. 

These results indicate amides, C5-C9, N-[3-(dimethylamino) propyl] were negative in the 

Bacterial Reverse Mutation Assay with a Confirmatory Assay under the conditions, and 

according to the criteria, of the test protocol. (OPPTS Test Guideline 870.5100) 

Clastogenicity

An In Vivo Mouse Bone Marrow Micronucleus Assay (OPPTS 870.5395) was conducted on IRC 

(CD-1) male mice with a dose level of 200, 400, or 800 mg/kg. Mortality was observed in 4 of 

13 males at 800 mg/kg. Amides, C5-C9, N-[3-(dimethylamino) propyl] induced signs of clinical 

toxicity in one male at 800 mg/kg, which included squinted eyes and labored respiration. 

Amides, C5-C9, N-[3-(dimethylamino) propyl] did not induce statistically significant increases 

in micronucleated polychromatic erythrocytes (PCEs) at any dose level examined (200, 400, and 

800 mg/kg). Additionally, amides, C5-C9, N-[3-(dimethylamino) propyl] was not cytotoxic (i.e., 

no statistically significant decreases in the PCE: normochromatic erythrocytes (NCE) ratios) to 

the bone marrow. Therefore, it is concluded that amides, C5-C9, N-[3-(dimethylamino) propyl] 

is negative for clastogenicity. 

Carcinogenicity

Although there are no animal carcinogenicity studies available in the database, amides, C5-C9, 

N-[3-(dimethylamino) propyl] tested negative in mutagenicity and clastogenicity assays and no 

evidence of specific target organ toxicity was observed in the OPPTS Harmonized Test 

Guideline 870.3650 study. A qualitative structure activity relationship database, DEREK Version 

11, was used to determine if there were structural alerts suggestive of carcinogenicity. No 

structural alerts were identified for the parent AADPAs nor its major metabolite 

dimethylaminopropylamine (DMAPA). Additionally, no evidence of carcinogenicity was 

observed in studies on the metabolite dimethylaminopropylamine. The Agency does not 
11 

anticipate amides, C5-C9, N-[3-(dimethylamino) propyl] or amides, C6-C12, N-[3-

(dimethylamino) propyl] to be carcinogenic; therefore, a carcinogenicity assessment was not 

performed. 

Metabolism and Pharmacokinetics

According to the petitioner: 

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. 

DMAPA has been assessed by the Agency as an inert ingredient and is exempt from tolerance 

under 40 CFR 180.920 and 180.930 (Federal Register, August 5, 2009 (74 FR 38924-35). 

Toxicity Endpoint Selection: 

No acute endpoint of concern was identified in the available database. The point of departure for 

this risk assessment for all durations and routes of exposure was from the OPPTS Harmonized 

Test Guideline 870.3650 toxicity study in rats. The NOAEL is 175 mg/kg/day and the LOAEL is 

600mg/kg/day based on body weight decreases and food consumption for both sexes and lower 

absolute and relative-to-brain ovary, uterus, and pituitary weights for the reproductive phase 

females. A 100 fold uncertainty factor was used for the chronic exposure (10X interspecies 

extrapolation, 10X for intraspecies variability and 1X FQPA factor). 

Although a NOAEL of 150 mg/kg/day was observed in the 28-day range finding study, the 

Agency believes that this NOAEL was an artifact of the large dosing gap between the NOAEL of 

150 and the LOAEL of 500 mg/kg/day. In the subsequent 90-day study a dose of 175 mg/kg/day 

was found to be the NOAEL with the LOAEL of 600 mg/kg/day. In addition, a 28-day range 

finding study in rats resulted in a NOAEL of 300 mg/kg/day and a LOAEL of 800 mg/kg/day. 

The Agency feels that 175 mg/kg/day more accurately represents the true NOAEL. 
12 

The NOAEL of 175 mg/kg/day was used as the endpoint for all exposure durations via oral, 

dermal, and inhalation routes of exposure. The residential, occupational, and aggregate level of 

concern (LOC) is for margins of exposure (MOE) that are less than 100 and is based on 10X 

interspecies extrapolation, 10X for intraspecies variability and 1X FQPA factor. Dermal 

absorption is estimated to be 25% based on the large molecular weight of the chemical and 

information available to the Agency regarding dermal absorption from pesticidal chemicals. Due 

to the vapor pressure of the chemicals they are not expected to volatilize; however, in an effort to 

capture all potential exposures, in the absence of confirmatory data, the Agency has assumed a 

100% inhalation exposure. 

IV. FQPA SAFETY FACTOR 

FFDCA section 408 provides that EPA shall apply an additional tenfold margin of exposure 

(safety) for infants and children in the case of threshold effects to account for prenatal and 

postnatal toxicity and the completeness of the database on toxicity and exposure unless EPA 

determines that a different margin of exposure (safety) will be safe for infants and children. This 

additional margin of safety is commonly referred to as the FQPA Safety Factor (SF). In applying 

this provision, EPA either retains the default value of 10X, or uses a different additional safety 

factor when reliable data are available. 

Reproductive and developmental effects were evaluated in a 90-day study conducted on 

Sprague-Dawley (CD) rats (MRID 48117116). No evidence of toxicity was noted at exposure 

levels of 15, 50, and 175 mg/kg/day. Systemic toxicity including lower mean body weights, body 

weight gains, and food consumption for both sexes and lower absolute and relative-to-brain 

ovary, uterus, and pituitary weights for the reproductive phase females was exhibited at 600 

mg/kg/day. In addition, lower mean live litter size on PND 0, number of pups born and 

implantation sites, and lower mean pup weights were noted in the 600 mg/kg/day group. 

Therefore, the systemic, reproductive, and developmental NOAELs were considered to be 175 

mg/kg/day. All reproductive and developmental effects were noted in the presence of maternal 

toxicity; therefore, there was no evidence of increased susceptibility in infants and children. 

No evidence of neurotoxicity or immunotoxicity was observed in the database. In addition, an 

OECD 421 reproduction and developmental toxicity screening test using the metabolite 

dimethylaminopropylamine in Sprague-Dawley rats resulted in parental toxicity at 200 

mg/kg/day based on decreased body weight gain and clinical signs (respiratory sounds and 

piloerection). Reproductive and developmental toxicity were not observed at any dose level.

The FQPA factor can be reduced to 1X for the following reasons: 

• The toxicology database is adequate for assessing the sensitivity of infants and children 

to exposure from amides, C5-C9, N-[3-(dimethylamino) propyl] and amides, C6-C12, N-[3-

(dimethylamino) propyl] and its metabolite, dimethylaminopropylamine. 

• No susceptibility was demonstrated in the offspring in the OECD 422 study following 

prenatal and potential post-natal exposure. 

• No susceptibility was demonstrated in the offspring in the OECD 421 study with the 

metabolite, dimethylaminopropylamine, following prenatal and post-natal exposure. 

 • No evidence of neurotoxicity was demonstrated in the database and there is no need for 

a developmental neurotoxicity study or additional UFs to account for neurotoxicity. 
13 

 • Amides, C5-C9, N-[3-(dimethylamino) propyl] tested negative in mutagenicity and 

clastogenicity assays and no evidence of specific target organ toxicity was observed in the 

OPPTS Harmonized Test Guideline 870.3650 study. No structural alerts for carcinogenicity were 

detected in the Derek model estimation. In addition, no evidence of carcinogenicity was 

observed in studies on the metabolite dimethylaminopropylamine. Therefore, there is no need to 

add additional uncertainty factors for the lack of carcinogenicity study.

• Residue values used in the dietary risk assessment and exposure values used in the 

residential assessment are unlikely to underestimate risk. 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% crop treated is assumed for all crops. 

EPA also made conservative (protective) assumptions in the ground and surface water modeling 

used to assess exposure to AADPAs in drinking water 

Based on the above weight of evidence EPA concluded that the FQPA factor could be 

reduced to 1X. 

V. ENVIRONMENTAL FATE AND EFFECTS 

In order to evaluate the environmental fate of amides, C5-C9, N-[3-(dimethylamino) propyl] and 

amides, C6-C12, N-[3-(dimethylamino) propyl] the Agency used experimental data submitted by 

the petitioner and, where data gaps were found, the EPISuiteTM Model was used. 

Amides, C5-C9, N-[3-(dimethylamino) propyl] and amides, C6-C12, N-[3-(dimethylamino) 

propyl] are expected to have low mobility in soil, the preferred media (Table 3). 

Adsorption/desorption studies (MRID 48117102) were conducted in five soils and results further 

indicated that the chemical is considered to be non-mobile in soil and have a very low potential 

to move to groundwater. Although these chemicals are highly soluble in water (Table 1) they are 

unlikely to reach drinking water sources due to their strong soil binding and rapid degradation. 

Therefore, the Agency does not believe that there is an increased risk of exposure to AADPAs 

via drinking water from the intended use of these chemicals as inert ingredients in pesticide 

products. 

The model predictions (e.g. Henry’s Law constant and vapor pressure, Table 1) indicate that 

AADPAs are unlikely to volatilize and therefore, inhalation exposure is not expected. A closed 

bottle biodegradation study (MRID 48205701) was conducted on the test chemical and resulted 

in 84% biodegradation at day 28, indicating that the chemical is readily biodegradable. Based on 

the results of the modeled EPISuiteTM data (Table 3) these chemicals have a low potential for 

bioaccumulation. Study results indicate no evidence of hydrolysis at pH 4, pH7, or pH 9 at 50°C, 

(MRID 481171-03); therefore, aqueous abiotic hydrolysis is not expected to be a significant 

route of elimination of AADPAs from the environment. 
14 

Table 3: AADPA Environmental Fate Characteristics 

Parameter Results Source 

Biodegradation readily biodegradable MRID 48117104 

Fugacity (Level III Model) EPISuiteTM 

 Air (%) 6.9 E -4 (e) 

 Water (%) 13.6 (e) 

 Soil (%) 86.2(e) 

 Sediment (%) 0.22(e) 

Bioaccumulation (BCF) 8.9 L/kg wet wt EPISuiteTM 

U.S. EPA. 2009. Estimation Programs Interface SuiteTM for Microsoft® Windows, v 4.0. United States Environmental 

Protection Agency, Washington, DC, USA. http://www.epa.gov/opptintr/exposure/pubs/episuite.htm

VI. RESIDENTIAL (Non-Occupational) EXPOSURE 

Dietary: 

Exposure to amides, C5-C9, N-[3-(dimethylamino) propyl] and amides, C6-C12, N-[3-

(dimethylamino) propyl] will be primarily through the oral route of exposure when eating food 

treated with pesticides containing the inert ingredient. In order to estimate the exposure from oral 

exposure to AADPAs the EPA’s I-DEEM model was used. See Table 4 for a summary of the 

results and Appendix A for the complete I-DEEM results. A complete description of the general 

approach taken to assess inert ingredient dietary risks in the absence of residue data is contained 

in the memorandum entitled “Alkyl Amines Polyalkoxylates (Cluster 4): Acute and Chronic 

Aggregate (Food and Drinking Water) Dietary Exposure and Risk Assessments for the Inerts.” 

(D361707, S. Piper, 2/25/09) and can be found at http://www.regulations.gov in docket ID 

number EPA-HQ-OPP-2008-0738. 

The I-DEEM is a highly conservative model with the assumption that the residue level of the 

inert ingredient would be no higher than the highest tolerance for a given commodity. Implicit in 

this assumption is that there would be similar rates of degradation between the active and inert 

ingredient (if any) and that the concentration of inert ingredient in the scenarios leading to these 

highest of tolerances would be no higher than the concentration of the active ingredient. The IDEEM assumes the inert ingredients will be 50% of the pesticide product. 

The Agency believes the assumptions used to estimate dietary exposures lead to a very 

conservative assessment of dietary risk for the following reasons: 

 the highest tolerance level residues from the surrogate pesticides for every food is used; 

 100% crop treated (%CT) is assumed for all crops (every food eaten by a person each day 

has tolerance-level residues); 

 many of these high tolerances are based on very short pre-harvest intervals where there is 

little time for degradation, whereas actual pesticide applications occur throughout the 

growing season; 

 no consideration was given to potential degradation between harvest and consumption 

(use of tolerance level residues which are typically one to two orders of magnitude higher 

than actual residues found in monitoring data); 
15 

 residue values were assigned to every commodity in DEEMTM with no consideration 

given to potential reduction in residues from washing or cooking. 

Although sufficient information to quantify actual residue levels in food is not available, the 

compounding of these conservative assumptions will lead to a significant exaggeration of actual 

exposures. OPP does not believe that this approach underestimates exposure in the absence of 

residue data. 

The dietary exposure for the US population was 10.9% of the RfD which is within the Agency’s 

acceptable level of concern. The most highly exposed subpopulation was children 1-2 years old 

at 35.7% of the cPAD. It is important to bear in mind that the I-DEEM model assumes a default 

value of 100 ppb for the concentration of the inert in all sources of drinking water. Based on the 

physical and chemical properties of these chemicals and the intended use pattern, exposure 

through drinking water is unlikely; therefore, these results are highly conservative in regard to 

the exposure through drinking water. 

Table 4: Summary of Dietary (Food and Drinking Water) Exposure and Risk for AADPA 

Population Subgroup 

Acute Dietary 

(95th Percentile) 

Chronic Dietary 

Dietary Exposure 

(mg/kg/day) % aPAD Dietary Exposure (mg/kg/day) % cPAD 

General U.S. Population 

No acute endpoint selected 

0.192 10.9 

All Infants (< 1 year old) 0.397 22.7 

Children 1-2 years old 0.624 35.7 

Children 3-5 years old 0.462 26.4 

Children 6-12 years old 0.255 14.6 

Youth 13-19 years old 0.144 8.2 

Adults 20-49 years old 0.144 8.3 

Adults 50+ years old 0.152 8.7 

Females 13-49 years old 0.145 8.3 

The most highly exposed subgroup is bolded. 

Residential Handler Exposure: 

A screening level residential exposure and risk assessment was completed for products that may 

contain AADPA inert ingredients in the future. Details of the assumptions informing the 

residential exposure and risk assessment can be found in “JITF Inert Ingredients. Residential 

and Occupational Exposure Assessment Algorithms and Assumptions Appendix for the Human 

Health Risk Assessments to Support Proposed Exemption from the Requirement of a Tolerance 

When Used as Inert Ingredients in Pesticide Formulations”, D364751, 5/7/09. A summary of the 

residential exposure and risk assessment is presented below. 
16 

The Agency selected representative scenarios, based on end-use product application methods and 

labeled application rates. Although there are no known or anticipated residential uses for 

AADPAs, in order to be protective of any future uses, a screening level exposure assessment was 

performed using high-end exposure scenarios for outdoor residential uses. These inerts may 

potentially be used in pesticide formulations that are used around the home. Residential pesticide 

products are typically formulated as liquids in concentrates or as wettable powders. The Agency 

did not assess risk for residential antimicrobial products, paint products, pet use products, or 

greenhouse uses. This assessment represents high-end outdoor residential exposure scenarios by 

assessing AADPA in pesticide formulations (fungicides/insecticides/herbicides) in outdoor use 

products. 

The mixer/loader/applicator high exposure outdoor scenarios use data from the Outdoor 

Residential Exposure Task Force: 

 Liquid products: Low Pressure Handwand (ORETF data) 

 Liquid products: Hose End Sprayer (ORETF data) 

 Ready to Use (RTU): Trigger Pump Sprayer Applications (ORETF data) 

The level of concern (LOC) for these risk assessments is an MOE of 100 based on the standard 

10X inter-species and 10X intra-species extrapolation safety factors. 

Exposure Data and Assumptions: 

A series of assumptions and exposure factors served as the basis for completing the residential 

handler risk assessments for the AADPA inerts. In addition to these factors, unit exposures were 

used to calculate risk estimates. The Agency used assumptions based on the Residential 

Exposure Assessment Standard Operating Procedures (Residential SOPs). Key assumptions used 

in this assessment are summarized below. 

 The maximum application rate for the inert based on its use in a class of pesticide 

(herbicide/insecticide/fungicide) has been assessed for the short-term exposure duration. 

 Residential risk assessments are based on high-end estimates of what homeowners would 

typically treat. Per the Office of Pesticide’s Health Effects Division’s (HED) Residential 

SOPs (1997 & 2001 revision), residential pesticide handlers are assumed to mix and use a 

volume of 5 gallons of product per day. 

 For adult exposure, the mean bodyweight for US males and females was used to estimate 

exposure (70 kg). 

 Only adults (age 18+) are expected to apply pesticides. 

 For outdoor pesticide applications, residential handlers are assumed to use a total of 2.25 

lbs AADPAs per day. This estimate is based on the following assumptions: 

o Five (5) gallons of formulated pesticide solution are assumed to be used per day 

by a residential handler (Revised Residential SOPs Area Treated, February, 

2001). Consistent with the residential SOPs, the density of the formulated 

pesticide solution is assumed to be 9 lbs/gallon. The amount of AADPA inert in 

the pesticide products is 50%. Therefore 50% of any pesticidal product is 
17 

5 gallons formulated pesticide solution*(9 lbs/gallon)*(50% AADPAs)*(1 part product concentrate/10 parts 

water) = 2.25 lbs AADPAs in formulated pesticide solutions per day

assumed to be AADPAs. Product concentrates are assumed to be diluted at a 1 to 

10 ratio with water. 

 Residential exposure is assessed assuming clothing consisting of a short-sleeved shirt, 

short pants and no gloves or respiratory protection, the typical clothing for a home-owner 

applicator 

 A 25% dermal absorption value was used. 

The duration of exposure for most homeowner applications of home garden and lawn care 

products is best represented by the short-term duration (1 to 30 days). These exposure scenarios 

include the application of herbicides to lawns and insecticides/fungicides to gardens, ornamental 

plants, or lawns. While these types of applications may be applied on consecutive days, they are 

not likely to exceed 30 consecutive application days. 

Risk Summary: 

For all the outdoor residential handler scenarios, risk estimates are not of concern (i.e., MOEs are 

all greater than 100) for both the route-specific (dermal or inhalation) assessment and for the 

total MOE (dermal and inhalation combined). A summary of the results are provided in Table 5 

below. The Agency believes that the handler scenarios assessed represent worst-case exposures 

and risks resulting from use of outdoor pesticide products containing these inert ingredients in 

residential environments. 

Table 5: Short-term Exposure and Risks for Residential Handlers for AADPA

Exposure 

Scenario 

(Formulation/ 

Application)

Application 

Rate1 (lb 

inert/ 

gallon) 

Quantity 

Handled/ 

Treated per 

day2

Dermal 

Unit 

Exposure 

(mg/lb 

inert)3

Inhalation 

Unit 

Exposure 

(mg/ lb 

inert)3

Dermal 

Dose 

(mg/kg 

/day)4

Inhalation 

Dose 

(mg/kg/ 

day)5

Baseline 

Dermal 

MOE6

Baseline 

Inhalation 

MOE7

Total 

MOE8

Outdoor Products 

Liquids/ Low 

Pressure 

Handwand (ST) 

(ORETF data) 

0.45 lb/gal 5 gallons 38 0.003 0.305 9.6E-5 570 1,800,000 570 

Liquids/ Hose End 

Sprayer, Lawn 

(ST) 

(ORETF data) 

0.45 lb/gal 5 gallons 11 0.017 0.088 0.00055 2,000 320,000 2,000 

Liquids/ Trigger 

Sprayer/ Home 

Garden (ST) 

(ORETF data) 

0.45 lb/gal 5 gallons 54 0.0019 0.434 6.11E-5 400 2,900,000 400 

1

Application rates are based on maximum application rates of products containing AADPA inerts multiplied by 50% for outdoor 

products to convert from product application rate to inert application rate. 2

Quantity treated daily values are back-calculated from 5 gallons of product used per day (Revised Residential SOPs 2001) for 

outdoor products. 

3

Unit Exposure data sources are identified in the exposure scenario column. All exposure scenarios assess exposure reflecting 

applicators wearing short-sleeved shirts and shorts and no respiratory protection. 4

Daily Dermal Dose = (Dermal Unit Exposure (mg inert /lb inert) * Application Rate (lb /gal) * Quantity handled (gallons/day))/ 

Body Weight (70 kg) 

5

 Daily Inhalation Dose = (Inhalation Unit Exposure (mg inert / lb inert) * Application Rate (lb /gal) * Quantity handled 

(gallons/day)) / Body Weight (70 kg) 

6 Dermal MOE = PoD (NOAEL of 175 mg/kg/day)/ Daily dermal dose (mg/kg/day) corrected for 25% dermal absorption. 7 Inhalation MOE = PoD (NOAEL of 175 mg/kg/day) / Daily inhalation dose (mg/kg/day) 8

 Total MOE = 1/ [(1/ Dermal MOE) + (1/ inhalation MOE)] 
18 

Residential Post-application Exposure:

Residential post-application exposures result when bystanders, such as children come in contact 

with the AADPA inerts in areas where end-use products have recently been applied (e.g., treated 

lawns and gardens). The Agency selected representative scenarios, based on end-use product 

application methods and labeled application rates, and conducted an assessment to represent 

worst-case residential exposure by assessing post application exposures and risks from AADPAs 

in pesticide formulations (fungicides/ insecticides/ herbicides) used in outdoor scenarios. The 

following post-application high end outdoor exposure scenarios were assessed: 

 Dermal exposure to treated lawns (adults/children)

 Hand-to-Mouth activity for toddlers on treated lawns (children)

 Object-to-Mouth activity for toddlers on treated lawns (children)

 Soil ingestion from treated soil (children)

The exposures from these routes and scenarios were considered individually and were also added 

together, where appropriate, to determine a total dose for children exposure to treated lawns. 

Residential post-application exposure is assessed on the day of application, typically referred to 

as Day 0. 

Inhalation exposures are not typically calculated for post-application scenarios because 

inhalation exposures generally account for a negligible percentage of the overall body burden for 

most pesticide chemicals. Any inhalation exposure through the post-application route will be less 

than the inhalation exposures assessed by residential handlers mentioned above. 

For all post-application exposure scenarios, exposures are assessed at short- and intermediateterm exposure durations because residues may be present on treated areas for lengths of time 

consistent with short- and intermediate-term exposure. 

Exposure Data and Assumptions: 

A series of assumptions and exposure factors served as the basis for completing the residential 

post-application risk assessments. The assumptions and factors used in the risk calculations are 

consistent with current Agency policy for completing residential exposure assessments (i.e., 

SOPs for Residential Exposure Assessment [1997 and 2001 revision]). 

Exposures to adults/children after contact with treated lawns have been addressed using the latest 

approaches for this scenario including: 

 For adult exposure, the mean bodyweight for US males and females was used to estimate 

exposure (70 kg). For child exposure, the mean of median values for male and female 3 

year olds was used to estimate exposure (15 kg). 

 HED has developed standard transfer coefficient (TC) values for residential postapplication scenarios to ensure consistency in exposure assessments. For the short-term 

assessment, TC values of 14,500 cm2

/hr (adults) and 5,200 cm2/hr (children) were used. 

For intermediate-term risk assessment, TC values of 7,300 cm2

/hr (adults) and 2,600 

cm

2

/hr (children) were used. These default transfer coefficients, found in the 2001 

Residential SOPs, were used to calculate post-application exposures. 
19 

 Based on HED’s Residential SOPs, it was assumed that the surface area used for each 

hand-to-mouth event is 20 cm2 (based on the surface area of three fingers of a toddler’s 

hand). For short-term exposures, it is assumed that there were 20 events per hour (90th

percentile, according to the SOP) and for intermediate-term exposures, it was assumed 

that there were 9.5 event/hour (mean value). 

 The exposure time used is 4 hours a day (USEPA, 2000 and 2001). 

 The saliva extraction efficiency used is 50% (USEPA, 2000 and 2001). 

 Pesticidal products are assumed to contain a maximum of 50% AADPAs by weight in the 

end use products. 

 The relevant application rates for products containing these inerts are derived above. 

 A 25% dermal absorption value was used. 

 Risk Summary: 

A summary of the residential post-application exposure and risk estimates are presented in Table 

6, below. Short- and intermediate-term post-application risks for children are not of concern. The 

individual route-specific and combined non-dietary risks from dermal exposure and hand-tomouth exposure for the outdoor scenarios do not demonstrate risks of concern for toddlers (i.e., 

the MOEs for the assessed scenarios are greater than 100) for both the short- and intermediateterm exposure durations. 

Table 6: Residential Post-application Short- and Intermediate-term Exposures and Risks for AADPAs

Exposure Scenario Application Rate1 Exposed 

Population & 

Exposure 

Duration2

Daily Dose 

(mg/kg/day)3

MOE4

Outdoor Lawn Products 

Dermal Exposure to 

Treated Lawns 

2.25 lb/day 

Adult ST 0.131 1,300 

Adult IT 0.0658 2,700 

Child ST 0.219 800 

Child IT 0.109 1,600 

Hand-to-Mouth from 

Treated Lawn 

Child ST 0.037 5,200 

Child IT 0.016 11,000 

Object-to-Mouth 

from Treated Lawn 

Child ST 0.0084 21,000 Child IT 

Soil Ingestion Child ST 0.000113 1,600,000 Child IT 

Total Lawn 

Combined 

Exposures* 

Child ST NA 690 

Child IT NA 1,400 

1 Application rates for outdoor products are derived in the “Residential Handler” section above. 2 ST and IT indicate short- or intermediate-term exposure durations. 3 Daily Dose = Daily Dose algorithms for various residential post-application scenarios outlined in “JITF Inert Ingredients. 

Residential and Occupational Exposure Assessment Algorithms and Assumptions Appendix for the Human Health Risk 

Assessments to Support Proposed Exemption from the Requirement of a Tolerance When Used as Inert Ingredients in Pesticide 

Formulations”, D364751, 5/7/09. 

4

 Dermal MOE = PoD (NOAEL of 175 mg/kg/day)/ Daily dermal dose (mg/kg/day) corrected for 25% dermal absorption. Oral 

MOE = PoD (NOAEL of 175 mg/kg/day) / Daily dose (mg/kg/day). 5

 Combined exposures reflect the aggregation of dermal exposure to treated areas and HTM exposure from treated areas (for 

children). Total Combined Exposures = 1/ [(1/ Dermal MOE) + (1/ HTM MOE)] 
20 

VII. AGGREGATE RISK ASSESSMENTS AND CHARACTERIZATION 

Although there is a potential for amides, C5-C9, N-[3-(dimethylamino) propyl] and amides, C6-

C12, N-[3-(dimethylamino) propyl] to produce the metabolite dimethylaminopropylamine 

(DMAPA), which is currently approved under 40 CFR 180.920 and 180.930, EPA does not 

anticipate any risk concerns from aggregate exposure to DMAPA for the following reasons: 

i. Evidence from toxicology studies indicates that metabolization of amides, C5-C9, N-

[3-(dimethylamino) propyl] and amides, C6-C12, N-[3-(dimethylamino) propyl], to DMAPA 

does not occur in significant amounts. The parent chemicals (i.e., amides, C5-C9, N-[3-

(dimethylamino) propyl] and amides, C6-C12, N-[3-(dimethylamino) propyl]) have a larger and 

more complete toxicity database which resulted in a higher NOAEL than the metabolite, 

DMAPA. The point of departure (NOAEL) selected for all exposure scenarios for amides, C5-

C9, N-[3-(dimethylamino) propyl] and amides, C6-C12, N-[3-(dimethylamino) propyl] is 175 

mg/kg/day versus the NOAEL of 50 mg/kg/day for DMAPA. If DMAPA is a major metabolite 

of amides, C5-C9, N-[3-(dimethylamino) propyl] and amides, C6-C12, N-[3-(dimethylamino) 

propyl] then the toxicity endpoints for amides, C5-C9, N-[3-(dimethylamino) propyl] and 

amides, C6-C12, N-[3-(dimethylamino) propyl] and DMAPA would be comparable. 

ii. The previous risk assessment of metabolite DMAPA (as inert ingredient) indicates that 

any marginal increase in DMAPA exposure as a result of the use of amides, C5-C9, N-[3-

(dimethylamino) propyl] and amides, C6-C12, N-[3-(dimethylamino) propyl] would not alter the 

DMAPA risk significantly nor change EPA’s conclusion regarding the safety of DMAPA. 

[Federal Register August 5, 2009 (74 FR 38924) (FRL-8430-2)] 

Acute Aggregate Risk: 

There was no hazard attributable to a single exposure in the toxicity database for the amides, C5-

C9, N-[3-(dimethylamino) propyl] and amides, C6-C12, N-[3-(dimethylamino) propyl]; 

therefore, an acute aggregate risk assessment is not required. 

Short-Term/Intermediate-Term Aggregate Risk: 

Short-term and intermediate-term aggregate risk assessments for the AADPA inert ingredients 

combine high end residential short- or intermediate-term exposures with average food and 

drinking water exposures, and compare this total to a short- or intermediate-term PoD. Short- and 

intermediate-term residential exposures are summarized in Table 7. 
21 

Table 7: Short- and Intermediate-Term Residential Risks for the AADPA Aggregate Risk Calculations 

Population Handler Risk (MOE)1 Post-application Risk 

(MOE) 

Residential Risk 

(MOE)2

 Short-Term 

Adult Male 

400 

Source: Table 5 

Liquid/Trigger Sprayer/Home 

Garden (ST) 

1,300 

Source: Table 6 

ST Dermal Exposure to Treated 

Lawns 

300 

Adult Female 

400 

Source: Table 5 

Liquid/Trigger Sprayer/Home 

Garden (ST)

1,300 

Source: Table 6 

ST Dermal Exposure to Treated 

Lawns 

300 

Child N/A 

690 

Source: Table 6 

 ST Total Lawn Combined 

Exposures 

690 

Intermediate-Term 

Adult Male N/A 

2,700 

Source: Table 6 

IT Dermal Exposure to Treated 

Lawns

2,700 

Adult Female N/A 

2,700 

Source: Table 6 

IT Dermal Exposure to Treated 

Lawns

2,700 

Child N/A 

1,400 

Source: Table 6 

IT Total Lawn Combined 

Exposures

1,400 

1 – Handler exposure combines high end dermal and inhalation handler exposure, where the exposure duration is appropriate to 

assess 

2 - Residential exposure combines high end dermal and inhalation handler exposure for short-term (Table 5) with high end post 

application dermal and incidental oral exposure (Table 6). 
22 

Short- and intermediate-term aggregate risks are summarized in Table 8. Short- and 

intermediate-term aggregate risks are not of concern for adults or children. 

Table 8: Short-Term and Intermediate-Term Aggregate Risk Calculations 

Population 

LOC for 

Aggregate 

Risk1

MOE 

food & water2

MOE 

residential3

Aggregate MOE 

(food and 

residential)4

 Short-Term 

Adult Male 100 1200 300 240 

Adult Female 100 1200 300 240 

Child 100 280 690 200 

Intermediate-Term 

Adult Male 100 1200 2,700 830 

Adult Female 100 1200 2,700 830 

Child 100 280 1400 230 1 The LOC is based on the standard 100X safety factor for inter- and intra-species extrapolation. 2 MOE food = [(short- or intermediate-term oral NOAEL)/(chronic dietary exposure)]. Chronic dietary exposure values from 

Table 4. 

3 MOE residential from Table 7. 4 Aggregate MOE (food and residential) = 1[(1MOE food) + (1MOE residential)] 

Long-Term Aggregate Risk: 

For the AADPAs, the long-term aggregate risk includes dietary exposures to food and drinking 

water only. Long-Term (chronic) aggregate risks for the AADPAs are not of concern. 

 Cancer Risk: 

The Agency has not identified any concerns for carcinogenicity; therefore, an aggregate cancer 

dietary exposure assessment was not performed. 

VIII. OCCUPATIONAL EXPOSURE/RISK PATHWAY 

 

 Occupational Handler Exposure: 

 

Based on examination of product labels which could potentially contain the AADPAs as inert 

ingredients, the Agency has determined that exposure to handlers can occur in a variety of 

occupational environments. Details of the occupational exposure assessment for the AADPA 

inerts can be found in the document “JITF Inert Ingredients. Residential and Occupational 

Exposure Assessment Algorithms and Assumptions Appendix for the Human Health Risk 

Assessments to Support Proposed Exemption from the Requirement of a Tolerance When Used 

as Inert Ingredients in Pesticide Formulations”, D364751,” 5/7/09. 

The representative occupational scenarios selected by the Agency for assessment were evaluated 

based on likely maximum application rates for products which may contain the AADPA inerts 
23 

for the short-term exposure assessment and average application rates for products likely to 

contain AADPAs as inerts for the intermediate- and long-term exposure durations. Active 

ingredient application rates were corrected for the maximum amount of AADPAs likely to be in 

the final formulations to determine exposure and risk from exposure to AADPAs grouped by 

fungicide/insecticide or herbicide. A summary of the occupational assessment is presented 

below. 

Exposure to pesticide handlers is likely during the occupational use of pesticides containing the 

AADPA inert ingredients. Dermal and inhalation exposure was estimated using the Occupational 

Pesticide Handler Unit Exposure Surrogate Reference Table published May 4, 2011. The 

quantitative exposure/risk assessment developed for occupational handlers to support the 

requested exemption from the requirement of a tolerance for the AADPAs is based on the 

following scenarios. The Agency notes that these scenarios were selected to represent the 

scenarios with the highest potential exposure. 

1) Mixer/Loader for aerial application- high acreage field crops (liquids) 

2) Mixer/Loader for airblast application- tree nuts crops (both liquid and wettable 

powder) 

3) Mixer/Loader for groundboom application- high acreage field crops and turf (liquids 

and wettable powder) 

4) Applicators for aerial application- high acreage field crops (liquid) 

5) Applicators for airblast- tree nut crops 

6) Applicators for groundboom- high acreage field crops and turf 

7) Mixer/Loader/Applicator- low pressure handwand (liquids and wettable powders) 

8) Flagging- high acreage field crops (liquids) 

Risk estimates were calculated using the Margin of Exposure (MOE) which is a ratio of the 

toxicological PoD to the daily dose. The level of concern (LOC) for these risk assessments is an 

MOE of 100 based on the standard 10X inter and 10X intra species uncertainty safety factors. 

Daily dose values are calculated by first calculating exposures by considering application 

parameters (i.e., rate and area treated) along with unit exposures. Exposures are then normalized 

by body weight to calculate dose levels. Dermal short- and intermediate-term exposure is 

compared to the dermal PoD of 175 mg/kg/day. A 25% dermal absorption value was used. 

Inhalation short- and intermediate-term exposure is compared to the inhalation PoD of 175 

mg/kg/day (same PoD for short- and intermediate-term exposure durations). To assess handler 

risks, the Agency used surrogate unit exposure data from the Occupational Pesticide Handler 

Unit Reference Table. 

Exposure Data and Assumptions:

The following assumptions and factors were used in order to complete the exposure and risk 

assessment for occupational handlers/applicators: 

 All worker scenarios were assumed to be short- and intermediate-term in exposure 

durations (i.e., 1-30 days and 1-6 months) except the greenhouse/hothouse scenario. 

 For scenarios where greenhouse/hothouse applications are possible, long-term exposure 

(6+ months) was assessed. 

 The exposure assessment assumes an 8 hour work day. 
24 

 The maximum application rate per pesticide group (herbicide/insecticide/fungicide) has 

been assessed for the short-term exposure duration. 

 The average application rate per pesticide group (herbicide/insecticide/fungicide) has 

been assessed for the intermediate-term exposure duration. 

 For adult exposure, the mean for US male and female bodyweights was used to estimate 

exposure (70 kg). 

 The baseline clothing level for occupational exposure scenarios is considered to be an 

individual wearing long pants, a long-sleeved shirt, shoes, socks, no chemical-resistant 

gloves, and no respiratory protection. 

 For high acreage crops (e.g. corn, soybeans) where applicators can mix/load large 

quantities of pesticide, exposure assessments have also been completed for baseline 

dermal PPE (Personal Protective Equipment) plus chemical-resistant gloves, and no 

respiratory protection. 

 There is no proposed limit to the amount of AADPA inerts in the pesticide products. 

Therefore 50% of any pesticidal product is assumed to be AADPAs (assuming that the 

inert ingredient would be in the formulation at a level equivalent to the active ingredient 

(50% active ingredient; 50% AADPA). 

 Risk Characterization:

The Agency initially assessed handler exposure and risks for the AADPA inerts in fungicides, 

herbicides and insecticides at baseline PPE (long pants, a long-sleeved shirt, shoes, socks, no 

chemical-resistant gloves, and no respiratory protection) which the Office of Pesticides (OPP) 

considers to be standard agricultural worker clothing. When these assessments indicated that 

there were potential risks of concern for scenarios where workers would be handling large 

quantities of pesticide for high volume operations typically involving aerial applications to high 

acreage crops, we repeated the assessments and included additional PPE (i.e., chemical-resistant 

gloves for pesticide handlers). See Table 9A and 9B for herbicide products, Table 10A and 10B 

for insecticide products, and Table 11A and 11B for fungicide products. The Agency has 

included an assessment for workers handling high volumes of chemicals, which includes gloves, 

as the Agency believes workers handling these volumes of pesticides will be wearing chemicalresistant gloves. 

When handlers are wearing standard worker clothing (i.e., baseline PPE) the majority of 

occupational handler scenarios do not indicate risks of concern. For the occupational handler 

scenarios which involve the handling of large volumes of pesticides, those which EPA believes 

that handlers will be wearing chemical-resistant gloves, occupational handler scenarios do not 

indicate risks of concern with the addition of chemical-resistant gloves to baseline PPE (i.e., 

minimum dermal PPE). 

Pesticide usage in greenhouses has not been evaluated in this assessment and therefore, these 

inert ingredients are not permitted in pesticide formulations used in greenhouses. 

For the mixer/loader/applicator scenarios described in the occupational handler tables (below), 

the ORETF handler studies have no data for baseline dermal exposure because the handlers in 

the study wore gloves and no respiratory protection. HED believes baseline exposure is relevant 
25 

to assess for these exposure scenarios (i.e., baseline dermal PPE and no respiratory protection). 

Therefore, both ORETF and PHED scenarios are shown in the mixer/loader/applicator section of 

the occupational handler tables. Baseline inhalation MOEs are reported “as is” because ORETF 

study participants did not wear respiratory protection. Additional explanation of the ORETF 

studies, as well as additional information concerning the exposure scenarios assessed, is 

available in “JITF Inert Ingredients. Residential and Occupational Exposure Assessment 

Algorithms and Assumptions Appendix for the Human Health Risk Assessments to Support 

Proposed Exemption from the Requirement of a Tolerance When Used as Inert Ingredients in 

Pesticide Formulations”, D364751,” 5/7/09.

Table 9A: Exposure and Risks for Occupational Handlers of AADPAs in Herbicide Products (All Exposure 

Durations) at Baseline Dermal PPE

Exposure Scenario 

(Formulation/ 

Application/ Crop) 

Application 

Rate1 (lb 

inert/ A) 

Area 

Treated 

Daily2 

(acres) 

Dermal 

Unit 

Exposure 

(mg/lb 

inert)3

Inhalation 

Unit 

Exposure 

(ug/ lb 

inert)3

Baseline 

Dermal 

Dose 

(mg/kg 

/day)4

Baseline 

Inhalation 

Dose 

(mg/kg/ 

day)5

Baseline 

Dermal 

MOE6

Baseline 

Inhalation 

MOE7

Total 

MOE8

Mixer/Loader Scenarios 

Liquids/ Aerial 

Application/ High Acreage 

Crops (ST) 

5.2 

1200 

0.22 0.219 

19.611 0.0195 36 9000 36 

Liquids/ Aerial 

Application/ High Acreage 

Crops (IT) 

1 3.771 0.00375 190 47000 180 

Liquids/ Airblast/ Nut Tree 

(ST) 3.6 

40 

0.453 0.00045 1500 390000 1500 

Liquids/ Airblast/ Nut Tree 

(IT) 1.6 0.201 0.0002 3500 870000 3500 

Liquids/ Groundboom/ 

High Acreage Crops (ST) 5.2 

200 

3.269 0.00325 210 54000 210 

Liquids/ Groundboom/ 

High Acreage Crops (IT) 1 0.629 0.00063 1100 280000 1100 

Liquids/ Groundboom/ 

Turf (ST) 5.2 

40 

0.654 0.00065 1100 270000 1100 

Liquids/ Groundboom/ 

Turf (IT) 1 0.126 0.00013 5600 1400000 5500 

Liquids/ Low Pressure 

Handwand/ Turf (ST) 3.6 

5 

0.0566 0.00006 12000 3100000 12000 

Liquids/ Low Pressure 

Handwand/ Turf (IT) 3.6 0.0566 0.00006 12000 3100000 12000 

Wettable Powder/ Airblast/ 

Nut Tree (ST) 0.8 

40 

3.7 43 

1.69 0.0197 410 8,900 400 

Wettable Powder/ Airblast/ 

Nut Tree (IT) 0.8 1.69 0.0197 410 8,900 400 

Wettable Powder/ 

Groundboom/ High 

Acreage Crops (ST) 

0.8 

200 

8.457 0.0983 83 1800 79 

Wettable Powder/ 

Groundboom/ High 

Acreage Crops (IT) 

0.5 5.286 0.0614 130 2,800 130 

Wettable Powder/ 

Groundboom/ Turf (ST) 0.8 

40 1.69 0.0197 410 8,900 4000 

Wettable Powder/ 

Groundboom/ Turf (IT) 0.5 1.057 0.0123 660 14,000 630 

Wettable powder/ Low 

Pressure Handwand/ Turf 

(ST) 

3.6 

5 

0.951 0.011 740 16,000 700 

Wettable powder/ Low 

Pressure Handwand/ Turf 

(IT) 

3.6 0.951 0.011 740 16,000 700 

Applicator Scenarios 

Liquid/ Aerial Application/ 

High Acreage Crops (ST)9 5.2 

1200 

Eng 

control 

only: 

0.0055 

Eng 

control 

only: 

0.068 

0.49 0.0061 1,400 29,000 1,400 

Liquid/ Aerial Application/ 

High Acreage Crops (IT)9 1 0.094 0.0012 7,400 150,000 7,100 

Airblast/ Nut Tree (ST) 0.8 40 0.36 4.5 0.1646 0.0021 4,300 85,000 4,100 
26 

Table 9A: Exposure and Risks for Occupational Handlers of AADPAs in Herbicide Products (All Exposure 

Durations) at Baseline Dermal PPE

Exposure Scenario 

(Formulation/ 

Application/ Crop) 

Application 

Rate1 (lb 

inert/ A) 

Area 

Treated 

Daily2 

(acres) 

Dermal 

Unit 

Exposure 

(mg/lb 

inert)3

Inhalation 

Unit 

Exposure 

(ug/ lb 

inert)3

Baseline 

Dermal 

Dose 

(mg/kg 

/day)4

Baseline 

Inhalation 

Dose 

(mg/kg/ 

day)5

Baseline 

Dermal 

MOE6

Baseline 

Inhalation 

MOE7

Total 

MOE8

Airblast/ Nut Tree (IT) 0.8 0.1646 0.0021 4,300 85,000 4,100 

Groundboom/ High 

Acreage Crops (ST) 5.2 

200 

0.014 0.74 

0.208 0.011 3,400 16,000 2,800 

Groundboom/ High 

Acreage Crops (IT) 1 0.04 0.0021 18,000 83,000 14,000 

Groundboom/ Turf (ST) 5.2 40 0.042 0.0022 17,000 80,000 14,000 

Groundboom/ Turf (IT) 1 0.008 0.00042 88,000 410,000 72,000 

Mixer/Loader/Applicator Scenarios 

Low Pressure Handwand/ 

Turf (ORETF data) (ST)10 3.6 

5 No Data 6.6 NA 0.0017 NA 100,000 NA 

Low Pressure Handwand/ 

Turf (ORETF data) (IT)10 3.6 NA 0.0017 NA 100,000 NA 

Wettable Powder/ Low 

Pressure Handwand/ 

Ornamentals (ST)10 3.6 

5 No Data 1100 

NA 0.2829 NA 620 NA 

Wettable Powder/ Low 

Pressure Handwand/ 

Ornamentals (IT)10 3.6 NA 0.2829 NA 620 NA 

Wettable Powder/ Low 

Pressure Handwand/ 

Ornamentals (LT)10 3.6 NA 0.2829 NA 620 NA 

Flagger Scenarios 

Liquid/ Flagger/ High 

Acreage Crops (ST) 5.2 

1200 0.011 0.35 0.981 0.0312 710 5,600 630 

Liquid/ Flagger/ High 

Acreage Crops (IT) 1 0.189 0.006 3,700 29,000 3,300 1

Application rates are based on maximum application rates of products that may contain these inerts multiplied by 50% to 

convert to application rate of just inert in a product (Pesticide products assumed to contain a maximum of 50% inert AADPAs). 

Application rates for Short-term (ST) exposure risk estimates are based on maximum application rates. Application rates for 

Intermediate-term (IT) and long-term (LT) exposures are based on average application rates. Baseline Dermal PPE is single 

layer clothing, no gloves. 

2

Area treated daily values are from the EPA HED estimates of acreage treated in a single day for each exposure scenario of 

concern. 

3

Unit Exposure values are reported in EPA’s Occupational Pesticide Handler Unit Exposure Surrogate Reference Table 

(OPHUE) dated May 4, 2011. All exposure scenarios assess baseline dermal PPE plus baseline inhalation exposure except for 

aerial applicator scenarios, which assess inhalation and dermal exposures with engineering controls. 

4

Daily Dermal Dose = (Dermal Unit Exposure (mg inert /lb inert) * Application Rate (lb inert /A) * Area Treated (A /day))/ Body 

Weight (70 kg) 

5

 Daily Inhalation Dose = (Inhalation Unit Exposure (μg inert / lb inert) * Conversion Factor (1 mg /1000 μg) * Application Rate

(lb inert /A) * Area Treated (A /day)) / Body Weight (70 kg) 

6 Dermal MOE = PoD (NOAEL of 175mg/kg/day)/ Daily dermal dose (mg/kg/day) corrected for 25% dermal absorption. 7 Inhalation MOE = PoD (NOAEL of 175 mg/kg/day) / Daily inhalation dose (mg/kg/day) 8

Total Combined MOE = 1/ [(1/ Dermal MOE) + (1/ inhalation MOE)] 9

Aerial applicators do not have baseline exposure: only engineering control exposure can be assessed. All other exposure 

scenarios assess baseline dermal (no gloves) plus baseline inhalation exposure. 10These scenarios have baseline inhalation unit exposures, but not baseline dermal unit exposures. The M/L/A scenario assessed 

has a higher unit exposure at baseline dermal exposure than either of the two scenarios shown at baseline PPE plus gloves dermal 

exposure.
27 

Table 9B: Exposure and Risks for Occupational Handlers of AADPAs in Herbicide Products (All Exposure Durations) with 

Baseline Dermal PPE and Gloves for High Acreage Mixer/ Loader Scenarios 

Exposure Scenario 

(Formulation/ 

Application/ Crop) 

Application 

Rate1 (lb 

inert/ A) 

Area 

Treated 

Daily2 

(acres) 

Dermal 

Unit 

Exposure 

(mg/lb 

inert)3

Inhalation 

Unit 

Exposure 

(ug/ lb 

inert)3

Min PPE 

Dermal 

Dose 

(mg/kg 

/day)4

Baseline 

Inhalation 

Dose 

(mg/kg/ 

day)5

Min PPE 

Dermal 

MOE6

Baseline 

Inhalation 

MOE7

Total MOE8

Mixer/Loader Scenarios 

Liquids/ Aerial 

Application/ High Acreage 

Crops (ST)9 5.2 1200 0.0376 0.219 3.352 0.0195 210 9000 200 

Wettable Powder/ 

Groundboom/ High 

Acreage Crops (ST) 

0.8 200 0.17 43 0.389 0.0983 1,800 1,800 900 

1

Application rates are based on maximum application rates of potential products containing AADPAs multiplied by 50% to 

convert to application rate of just inert in a product (Pesticide products assumed to contain a maximum of 50% inert AADPAs). 

Application rates for Short-term (ST) exposure risk estimates are based on maximum application rates. Application rates for 

Intermediate-term (IT) and long-term (LT) exposures are based on average application rates. Scenarios shown are with Baseline 

Dermal PPE plus gloves. 

2

Area treated daily values are from the EPA HED estimates of acreage treated in a single day for each exposure scenario of 

concern. 

3

Unit Exposure values are reported in OPHUE dated May 4, 2011. All exposure scenarios assess minimum dermal PPE (with 

gloves) plus baseline inhalation exposure. 

4

,

5

,

6 ,7, 8

 See Table 9A 9

 Exposure scenarios assess minimum dermal PPE (baseline PPE plus gloves) plus baseline inhalation exposure. 
28 

Table 10A: Exposure and Risks for Occupational Handlers of AADPAs in Insecticide Products (All Exposure 

Durations) at Baseline Dermal PPE

Exposure Scenario 

(Formulation/ 

Application/ Crop) 

Application 

Rate1 (lb 

inert/ A) 

Area 

Treated 

Daily2 

(acres) 

Dermal 

Unit 

Exposure 

(mg/lb 

inert)3

Inhalation 

Unit 

Exposure 

(ug/ lb 

inert)3

Baseline 

Dermal 

Dose 

(mg/kg 

/day)4

Baseline 

Inhalation 

Dose 

(mg/kg/ 

day)5

Baseline 

Dermal 

MOE6

Baseline 

Inhalation 

MOE7

Total 

MOE8

Mixer/Loader Scenarios 

Liquids/ Aerial 

Application/ High 

Acreage Crops (ST) 

1 

1200 

0.22 0.219 

3.771 0.00375 190 47000 180 

Liquids/ Aerial 

Application/ High 

Acreage Crops (IT) 

0.35 1.32 0.00131 530 130000 530 

Liquids/ Airblast/ Nut 

Tree (ST) 4.5 

40 

0.566 0.00056 1200 310000 1200 

Liquids/ Airblast/ Nut 

Tree (IT) 1.25 0.157 0.00016 4500 1100000 4400 

Liquids/ Groundboom/ 

High Acreage Crops (ST) 1 

200 

0.629 0.00063 1100 280000 1100 

Liquids/ Groundboom/ 

High Acreage Crops (IT) 0.35 0.22 0.055 3200 800000 3200 

Liquids/ Groundboom/ 

Turf (ST) 1 

40 

0.126 0.00013 5600 1400000 5500 

Liquids/ Groundboom/ 

Turf (IT) 0.35 0.044 0.00004 16000 4000000 16000 

Liquids/ Low Pressure 

Handwand/ Turf (ST) 3.6 

5 

0.0566 0.00006 12000 3100000 12000 

Liquids/ Low Pressure 

Handwand/ Turf (IT) 3.6 0.0566 0.00006 12000 3100000 12000 

Wettable Powder/ 

Airblast/ Nut Tree (ST) 3 

40 

3.7 43 

6.34 0.0737 110 2,400 110 

Wettable Powder/ 

Airblast/ Nut Tree (IT) 1.5 3.17 0.037 210 4,700 210 

Wettable Powder/ 

Groundboom/ High 

Acreage Crops (ST) 

0.8 

200 

8.457 0.098 83 1,800 79 

Wettable Powder/ 

Groundboom/ High 

Acreage Crops (IT) 

0.35 3.7 0.043 190 4,100 180 

Wettable Powder/ 

Groundboom/ Turf (ST) 0.8 

40 1.69 0.0197 410 8,900 400 

Wettable Powder/ 

Groundboom/ Turf (IT) 0.35 0.74 0.0086 950 20,000 900 

Wettable powder/ Low 

Pressure Handwand/ Turf 

(ST) 

3.6 

5 

0.951 0.011 740 160,000 700 

Wettable powder/ Low 

Pressure Handwand/ Turf 

(IT) 

3.6 0.951 0.011 740 160,000 740 

Applicator Scenarios 

Liquid/ Aerial 

Application/ High 

Acreage Crops (ST)9 1 

1200 

Eng 

control 

only: 

0.0055 

Eng 

control 

only: 

0.068 

0.094 0.0012 7,400 150,000 7,100 

Liquid/ Aerial 

Application/ High 

Acreage Crops (IT)9 0.35 0.033 0.0004 21,000 430,000 20,000 

Airblast/ Nut Tree (ST) 4.5 40 0.36 4.5 0.9257 0.0116 760 15,000 720 

Airblast/ Nut Tree (IT) 1.25 0.257 0.0032 2,700 54,000 2,600 

Groundboom/ High 

Acreage Crops (ST) 1 

200 

0.014 0.74 

0.04 0.00211 18,000 83,000 14,000 

Groundboom/ High 

Acreage Crops (IT) 0.35 0.014 0.00074 50,000 240,000 41,000 

Groundboom/ Turf (ST) 1 40 0.008 0.00042 88,000 410,000 72,000 

Groundboom/ Turf (IT) 0.35 0.0028 0.00015 250,000 1,200,000 210,000 

Mixer/Loader/Applicator Scenarios 

Low Pressure Handwand/ 

Turf (ORETF data) 

(ST)10 3.6 

5 NA 6.6 NA 0.0017 NA 100,000 NA 

Low Pressure Handwand/ 

Turf (ORETF data) (IT)10 3.6 NA 0.0017 NA 100,000 NA 

Wettable Powder/ Low 3.6 5 NA 1100 NA 0.2829 NA 620 NA 
29 

Table 10A: Exposure and Risks for Occupational Handlers of AADPAs in Insecticide Products (All Exposure 

Durations) at Baseline Dermal PPE

Exposure Scenario 

(Formulation/ 

Application/ Crop) 

Application 

Rate1 (lb 

inert/ A) 

Area 

Treated 

Daily2 

(acres) 

Dermal 

Unit 

Exposure 

(mg/lb 

inert)3

Inhalation 

Unit 

Exposure 

(ug/ lb 

inert)3

Baseline 

Dermal 

Dose 

(mg/kg 

/day)4

Baseline 

Inhalation 

Dose 

(mg/kg/ 

day)5

Baseline 

Dermal 

MOE6

Baseline 

Inhalation 

MOE7

Total 

MOE8

Pressure Handwand/ 

Ornamentals (ST)10

Wettable Powder/ Low 

Pressure Handwand/ 

Ornamentals (IT)10 3.6 NA 0.2829 NA 620 NA 

Wettable Powder/ Low 

Pressure Handwand/ 

Ornamentals (LT)10 3.6 NA 0.2829 NA 620 NA 

Flagger Scenarios 

Liquid/ Flagger/ High 

Acreage Crops (ST) 1 

1200 0.011 0.35 0.1886 0.006 3,700 29,000 3,300 

Liquid/ Flagger/ High 

Acreage Crops (IT) 0.35 0.066 0.0021 11,000 83,000 9,400 1

Application rates are based on maximum application rates of products containing inerts in AADPAs multiplied by 50% to 

convert to application rate of just inert in a product (Pesticide products assumed to contain a maximum of 50% inert AADPAs). 

Application rates for Short-term (ST) exposure risk estimates are based on maximum application rates. Application rates for 

Intermediate-term (IT) and long-term (LT) exposures are based on average application rates. Baseline Dermal PPE is single 

layer clothing, no gloves. 

2

Area treated daily values are from the EPA HED estimates of acreage treated in a single day for each exposure scenario of 

concern. 

3

Unit Exposure values are reported in OPHUE dated May 4, 2011. All exposure scenarios assess baseline dermal PPE plus 

baseline inhalation exposure except for aerial applicator scenarios, which assess inhalation and dermal exposures with 

engineering controls. 

4

Daily Dermal Dose = (Dermal Unit Exposure (mg inert /lb inert) * Application Rate (lb inert /A) * Area Treated (A /day))/ Body 

Weight (70 kg) 

5

 Daily Inhalation Dose = (Inhalation Unit Exposure (μg inert / lb inert) * Conversion Factor (1 mg /1000 μg) * Application Rate

(lb inert /A) * Area Treated (A /day)) / Body Weight (70 kg) 

6 Dermal MOE = PoD (NOAEL of 175 mg/kg/day)/ Daily dermal dose (mg/kg/day) corrected for 25% dermal absorption. 7 ST Inhalation MOE = PoD (NOAEL of 175 mg/kg/day) / Daily inhalation dose (mg/kg/day) 8

Total Combined MOE = 1/ [(1/ Dermal MOE) + (1/ inhalation MOE)] 9

Aerial applicators do not have baseline exposure: only engineering control exposure can be assessed. All other exposure 

scenarios assess baseline dermal (no gloves) plus baseline inhalation exposure. 10These scenarios have baseline inhalation unit exposures, but not baseline dermal unit exposures. The M/L/A scenario assessed 

has a higher unit exposure at baseline dermal exposure than either of the two scenarios shown at baseline PPE plus gloves dermal 

exposure. 

Table 10B: Exposure and Risks for Occupational Handlers of AADPAs in Insecticide Products (All Exposure Durations) with 

Baseline Dermal PPE and Gloves for High Acreage Mixer/ Loader Scenarios 

Exposure Scenario 

(Formulation/ 

Application/ Crop) 

Application 

Rate1 (lb 

inert/ A) 

Area 

Treated 

Daily2 

(acres) 

Dermal 

Unit 

Exposure 

(mg/lb 

inert)3

Inhalatio

n Unit 

Exposure 

(ug/ lb 

inert)3

Min PPE 

Dermal 

Dose 

(mg/kg 

/day)4

Baseline 

Inhalation 

Dose 

(mg/kg/ 

day)5

Min PPE 

Dermal 

MOE6

Baseline 

Inhalation 

MOE7

Total MOE8

Mixer/Loader Scenarios 

Wettable Powder/ 

Groundboom/ High 

Acreage Crops (ST) 

0.8 200 0.17 43 0.389 0.098 1,800 1,800 900 

1

Application rates are based on maximum application rates of potential products containing AADPAs multiplied by 50% to 

convert to application rate of just inert in an insecticide product (Insecticide products assumed to contain maximum of 50% 

AADPA inert). Application rates for Short-term (ST) exposure risk estimates are based on maximum application rates. 

Application rates for Intermediate-term (IT) and long-term (LT) exposures are based on average application rates. 2

Area treated daily are from the EPA HED estimates of acreage treated in a single day for each exposure scenario of concern. 

3

Unit Exposure values are reported in OPHUE dated May 4, 2011. All exposure scenarios assess minimum dermal PPE plus 

baseline inhalation exposure except for aerial applicator scenarios, which assess inhalation and dermal exposures with 

engineering controls. 

4

,

5

,

6

,

7

,

8 See Table 10A 9

 Exposure scenarios assess minimum dermal PPE (baseline PPE plus gloves) plus baseline inhalation exposure. 
30 

Table 11A: Exposure and Risks for Occupational Handlers of AADPAs in Fungicide Products (All Exposure 

Durations) at Baseline Dermal PPE

Exposure Scenario 

(Formulation/ 

Application/ Crop) 

Application 

Rate1 (lb 

inert/ A) 

Area 

Treated 

Daily2 

(acres) 

Dermal 

Unit 

Exposure 

(mg/lb 

inert)3

Inhalation 

Unit 

Exposure 

(ug/ lb 

inert)3

Baseline 

Dermal 

Dose 

(mg/kg 

/day)4

Baseline 

Inhalation 

Dose 

(mg/kg/ 

day)5

Baseline 

Dermal 

MOE6

Baseline 

Inhalation 

MOE7

Total MOE8

Mixer/Loader Scenarios 

Liquids/ Aerial 

Application/ High 

Acreage Crops (ST) 

2.5 

1200 

0.22 0.219 

9.429 0.0094 74 190000 74 

Liquids/ Aerial 

Application/ High 

Acreage Crops (IT) 

0.35 1.32 0.0013 530 130000 530 

Liquids/ Airblast/ Nut 

Tree (ST) 5.5 

40 

0.691 0.00069 1000 250000 1000 

Liquids/ Airblast/ Nut 

Tree (IT) 1.5 0.189 0.00019 3700 930000 3700 

Liquids/ Groundboom/ 

High Acreage Crops (ST) 2.5 

200 

1.571 0.00156 450 110000 440 

Liquids/ Groundboom/ 

High Acreage Crops (IT) 0.35 0.22 0.00022 3200 800000 3200 

Liquids/ Groundboom/ 

Turf (ST) 2.5 

40 

0.314 0.00031 2200 560000 2200 

Liquids/ Groundboom/ 

Turf (IT) 0.35 0.044 0.00004 16000 4000000 16000 

Liquids/ Low Pressure 

Handwand/ Turf (ST) 3.6 

5 

0.0566 0.00006 12000 3100000 12000 

Liquids/ Low Pressure 

Handwand/ Turf (IT) 3.6 0.0566 0.00006 12000 3100000 12000 

Wettable Powder/ 

Airblast/ Nut Tree (ST) 3.5 

40 

3.7 43 

7.4 0.086 95 2,000 90 

Wettable Powder/ 

Airblast/ Nut Tree (IT) 1 2.11 0.025 330 7,100 320 

Wettable Powder/ 

Groundboom/ High 

Acreage Crops (ST) 

0.5 

200 

5.29 0.0614 130 2,800 125 

Wettable Powder/ 

Groundboom/ High 

Acreage Crops (IT) 

0.3 3.17 0.0369 220 4,700 210 

Wettable Powder/ 

Groundboom/ Turf (ST) 0.5 

40 1.057 0.0123 660 14,000 630 

Wettable Powder/ 

Groundboom/ Turf (IT) 0.3 0.634 0.0074 1,100 24,000 1,100 

Wettable powder/ Low 

Pressure Handwand/ Turf 

(ST) 

3.6 

5 

0.95 0.011 740 16,000 700 

Wettable powder/ Low 

Pressure Handwand/ Turf 

(IT) 

3.6 0.95 0.011 740 16,000 700 

Applicator Scenarios 

Liquid/ Aerial 

Application/ High 

Acreage Crops (ST)9 2.5 

1200 

Eng 

control 

only: 

0.0055 

Eng 

control 

only: 

0.068 

0.236 0.0029 3,000 60,000 2,800 

Liquid/ Aerial 

Application/ High 

Acreage Crops (IT)9 0.35 0.033 0.0004 21,00 430,000 20,000 

Airblast/ Nut Tree (ST) 3.5 40 0.36 4.5 0.72 0.009 970 19,000 930 

Airblast/ Nut Tree (IT) 1.5 0.309 0.0039 2,300 45,000 2,200 

Groundboom/ High 

Acreage Crops (ST) 2.5 

200 

0.014 0.74 

0.1 0.0053 7,000 33,000 5,800 

Groundboom/ High 

Acreage Crops (IT) 0.35 0.014 0.0007 50,000 240,000 41,000 

Groundboom/ Turf (ST) 2.5 40 0.02 0.0011 35,000 170,000 29,000 

Groundboom/ Turf (IT) 0.35 0.0028 0.00015 250,000 1,200,000 210,000 

Mixer/Loader/Applicator Scenarios 

Low Pressure Handwand/ 

Turf (ORETF data) (ST)10 3.6 

5 No Data 6.6 NA 0.0017 NA 100,000 NA 

Low Pressure Handwand/ 

Turf (ORETF data) (IT)10 3.6 NA 0.0017 NA 100,000 NA 

Wettable Powder/ Low 

Pressure Handwand/ 3.6 5 No Data 1100 NA 0.2829 NA 620 NA 
31 

Table 11A: Exposure and Risks for Occupational Handlers of AADPAs in Fungicide Products (All Exposure 

Durations) at Baseline Dermal PPE

Exposure Scenario 

(Formulation/ 

Application/ Crop) 

Application 

Rate1 (lb 

inert/ A) 

Area 

Treated 

Daily2 

(acres) 

Dermal 

Unit 

Exposure 

(mg/lb 

inert)3

Inhalation 

Unit 

Exposure 

(ug/ lb 

inert)3

Baseline 

Dermal 

Dose 

(mg/kg 

/day)4

Baseline 

Inhalation 

Dose 

(mg/kg/ 

day)5

Baseline 

Dermal 

MOE6

Baseline 

Inhalation 

MOE7

Total MOE8

Ornamentals (ST)10

Wettable Powder/ Low 

Pressure Handwand/ 

Ornamentals (IT)10 3.6 NA 0.2829 NA 620 NA 

Wettable Powder/ Low 

Pressure Handwand/ 

Ornamentals (LT)10 3.6 NA 0.2829 NA 620 NA 

Flagger Scenarios 

Liquid/ Flagger/ High 

Acreage Crops (ST) 2.5 

1200 0.011 0.35 0.47 0.015 1,500 12,000 1,300 

Liquid/ Flagger/ High 

Acreage Crops (IT) 0.35 0.066 0.0021 11,000 83,000 9,400 1

Application rates are based on maximum application rates of potential products containing AADPAs multiplied by 50% to 

convert to application rate of just inert in a product (Pesticide products assumed to contain a maximum of 50% inert AADPA). 

Application rates for Short-term (ST) exposure risk estimates are based on maximum application rates. Application rates for 

Intermediate-term (IT) and long-term (LT) exposures are based on average application rates. Baseline Dermal PPE is single 

layer clothing, no gloves. 

2

Area treated daily values are from the EPA HED estimates of acreage treated in a single day for each exposure scenario of 

concern. 

3

Unit Exposure values are reported in OPHUE dated May 4, 2011. All exposure scenarios assess baseline dermal PPE plus 

baseline inhalation exposure except for aerial applicator scenarios, which assess inhalation and dermal exposures with 

engineering controls. 

4

Daily Dermal Dose = (Dermal Unit Exposure (mg inert /lb inert) * Application Rate (lb inert /A) * Area Treated (A /day))/ Body 

Weight (70 kg) 

5

 Daily Inhalation Dose = (Inhalation Unit Exposure (μg inert / lb inert) * Conversion Factor (1 mg /1000 μg) * Application Rate

(lb inert /A) * Area Treated (A /day)) / Body Weight (70 kg) 

6 Dermal MOE = PoD (NOAEL of 175 mg/kg/day)/ Daily dermal dose (mg/kg/day) corrected for 25% dermal absorption. 7 Inhalation MOE = PoD (NOAEL of 175 mg/kg/day) / Daily inhalation dose (mg/kg/day) 8

Total Combined MOE = 1/ [(1/ Dermal MOE) + (1/ inhalation MOE)] 9

Aerial applicators do not have baseline exposure: only engineering control exposure can be assessed. All other exposure 

scenarios assess baseline dermal (no gloves) plus baseline inhalation exposure. 10These scenarios have baseline inhalation unit exposures, but not baseline dermal unit exposures. The M/L/A scenario assessed 

has a higher unit exposure at baseline dermal exposure than either of the two scenarios shown at baseline PPE plus gloves dermal 

exposure. 
32 

Table 11B: Exposure and Risks for Occupational Handlers of AADPAs in Fungicide Products (All Exposure Durations) with 

Baseline Dermal PPE and Gloves for High Acreage Mixer/ Loader Scenarios 

Exposure Scenario 

(Formulation/ 

Application/ Crop) 

Application 

Rate1 (lb 

inert/ A) 

Area 

Treated 

Daily2 

(acres) 

Dermal 

Unit 

Exposure 

(mg/lb 

inert)3

Inhalation 

Unit 

Exposure 

(ug/ lb 

inert)3

Min PPE 

Dermal 

Dose 

(mg/kg 

/day)4

Baseline 

Inhalation 

Dose 

(mg/kg/ 

day)5

Min PPE 

Dermal 

MOE6

Baseline 

Inhalation 

MOE7

Total MOE8

Mixer/Loader Scenarios 

Liquids/ Aerial 

Application/ High Acreage 

Crops (ST)9 2.5 1200 0.0376 0.219 0.226 0.00131 430 190000 420 

Wettable Powder/ Airblast/ 

Nut Tree (ST) 3.5 40 0.17 43 0.34 0.086 2,100 2,000 1,000 

1

Application rates are based on maximum application rates of potential products containing AADPAs multiplied by 50% to 

convert to application rate of just inert in a fungicide product (Fungicide products assumed to contain maximum of 50% inert 

from the AADPAs). Application rates for Short-term (ST) exposure risk estimates are based on maximum application rates. 

Application rates for Intermediate-term (IT) exposures are based on average application rates. 

2

Area treated daily values are from the EPA HED estimates of acreage treated in a single day for each exposure scenario of 

concern. 

3

Unit Exposure values are reported in OPHUE dated May 4, 2011. All exposure scenarios assess minimum dermal PPE plus 

baseline inhalation exposure except for aerial applicator scenarios, which assess inhalation and dermal exposures with 

engineering controls. 

4

,

5,,6 ,7

,

8 See Table 11A 9

 Exposure scenarios assess minimum dermal PPE (baseline PPE plus gloves) plus baseline inhalation exposure. 

Post-application Occupational Risk: 

The Agency uses the term post-application to describe exposures that occur when individuals are 

present in an environment that has been previously treated with a pesticide (also referred to as reentry exposure). Such exposures may occur when workers enter previously treated areas to 

perform job functions, including activities related to crop production, such as scouting for pests 

or harvesting. Post-application exposure levels vary over time and depend on such things as the 

type of activity, the nature of the crop or target that was treated, the type of pesticide application, 

and the chemical’s degradation properties. In addition, the timing of pesticide applications, 

relative to harvest activities, can greatly reduce the potential for post-application exposure. 

This assessment is considered to be a screening level estimate, demonstrating that there are 

minimal potential risks to workers re-entering fields treated with pesticides containing the 

AADPAs as inert ingredients. Risks were calculated using the Margin of Exposure (MOE) 

approach, which is a ratio of the body burden to the toxicological PoD. The three occupational 

post-application scenarios assessed are for post-application activities associated with: 

 Tall field/row crops (including scouting, weeding, hand harvesting sweet corn) 

 Turf (golf course/sod farm) (including mowing, transplanting, hand weeding) 

 Vine/Trellis crops (including scouting, training, tying, thinning, and grape girding and 

cane turning) 

Inhalation exposures are not typically calculated for post-application scenarios because 

inhalation exposures generally account for a negligible percentage of the overall body burden for 

most pesticide chemicals. This is particularly true for chemicals with a low vapor pressure such 

as AADPAs. 
33 

Exposure Data and Assumptions: 

Key assumptions used in the post-application risk assessment calculations are detailed as 

follows: 

 The average occupational workday is assumed to be 8 hours. 

 For adult exposure, the mean for US male and female bodyweights was used to estimate 

exposure (70 kg). 

 HED has developed standard transfer coefficient values for occupational post-application 

scenarios to ensure consistency in exposure assessments. These standard values were 

used to calculate post-application exposures. 

 Anticipated post-application activities and their respective dermal transfer coefficients 

(TCs) are summarized in Table 12. The TC information is based on the Science Advisory 

Council for Exposure Policy Number 3.1. 

 TC for sod transplanting, hand weeding is from data using Agriculture Re-entry Task 

Force (ARF) Study ARF-035 (MRID 45432303). 

 Calculations of post-application exposures are completed using maximum application 

rates of the products of that type of pesticide (herbicide, insecticide, or fungicide) for 

short-term exposures and average application rates of products for intermediate-term 

exposures. 

 Herbicides/insecticides/fungicides assessed can contain a maximum of 50% AADPAs in 

any product formulation. 

 No post-application data were submitted for the AADPAs cluster; a default 20% of the 

application rate (for agricultural crops) and 5% (for turf) is considered available as a 

transferrable residue with a 10% default daily dissipation rate. 

 A 25% dermal absorption value was used. 

“JITF Inert Ingredients. Residential and Occupational Exposure Assessment Algorithms and 

Assumptions Appendix for the Human Health Risk Assessments to Support Proposed Exemption 

from the Requirement of a Tolerance When Used as Inert Ingredients in Pesticide Formulations”, 

D364751, 5/7/09 contains additional information about the exposure scenarios assessed in this 

document. 

A variety of pesticide formulations may potentially contain AADPAs as inert ingredients. PPE is 

usually not required for worker re-entry, and therefore these post-application risk estimates are 

based on baseline PPE (no gloves). Typically, the Agency characterizes the risk estimate in 

relation to the restricted entry interval (REI) for a particular active ingredient. However, since 

this assessment is to support an exemption from the requirement of a tolerance without a 

requirement for an REI, MOEs have been calculated on the day of application (Day 0). 

Risk Summary: 

Occupational post-application risk estimates are presented in Table 12. The risk estimates for a 

number of the scenarios assessed demonstrate risks of concern (i.e., MOEs < 100) for any of the 

assessed scenarios on Day 0. Those scenarios include: 

1) The short-term worker post-application activities involving herbicides on corn, 

specifically the hand-harvesting / detassling scenario. That scenario resulted in an MOE 
34 

of 31 on the day of application (Day 0). Assuming an herbicide application at the 

maximum application rate, the MOE would exceed 100 for this scenario at day 11 after 

application. The Agency notes that it is not expected to be typical agricultural practice to 

apply herbicides on the same day workers would be conducting hand harvesting and 

detassling activities. As noted earlier in this assessment, herbicides are typically applied 

relatively early in a growing season. 

2) The short-term worker post-application activities involving insecticides on corn, 

specifically the hand-harvesting / detassling scenario. That scenario resulted in an MOE 

of 32 on the day of application (Day 0). Assuming an insecticide application at the 

maximum application rate, the MOE would exceed 100 for this scenario at day 11 after 

application. The Agency notes that it is not expected to be typical agricultural practice to 

apply insecticides on the same day workers would be conducting hand harvesting and 

detassling activities. 

3) The short-term worker post-application activities involving insecticides on grapes, 

specifically the cane turning/girdle. That scenario resulted in an MOE of 78 on the day of 

application (Day 0). Assuming an insecticide application at the maximum application 

rate, the MOE would exceed 100 for this scenario at day 3 after application. The Agency 

notes that it is not expected to be typical agricultural practice to apply insecticides on the 

same day workers would be conducting cane turning/girdle. 

4) The short-term worker post-application activities involving fungicides on corn, 

specifically the hand-harvesting / detassling scenario. That scenario resulted in an MOE 

of 64 on the day of application (Day 0). Assuming an insecticide application at the 

maximum application rate, the MOE would exceed 100 for this scenario at day 5 after 

application. The Agency notes that it is not expected to be typical agricultural practice to 

apply insecticides on the same day workers would be conducting hand harvesting and 

detassling activities. 
35 

Table 12: Short- and Intermediate-Term Occupational Post-application Dermal Exposures and Risks for MOTs

Crop & 

Exposure 

Duration 

Application 

Rate 

(lb inert /A) Work Activity 

Transfer 

Coefficient1

(cm2/hr) 

Day after 

Treatment2

DFRt

(μg/cm2)

3

Daily Dose 

(mg/kg/day)4 MOE5

Herbicide Products 

Corn (ST) 5.2 

Scout, weed low 

foliage 100 0 

11.668 

0.0333 5200 

Scout, weed 

high foliage 400 0 0.1333 1300 

Scout, irrigate, 

weed high 

foliage 

1,000 0 0.3334 520 

Harvesting/ 

detassling 17,000 0 5.6672 31 

Days after Treatment where MOE > 100 11 

Corn (IT) 0.6 

Scout, weed low 

foliage 100 0 

1.346 

0.0038 45000 

Scout, weed 

high foliage 400 0 0.0154 11000 

Scout, irrigate, 

weed high 

foliage 

1,000 0 0.0385 4500 

Harvesting/ 

detassling 17,000 0 0.6539 270 

Grapes 

(Table) (ST) 2.4 

Hedge, irrigate, 

weed, scout, 

train, tie 

500 0 

5.385 

0.0769 2300 

Scout, train, tie 1,000 0 0.1539 1100 

Harvest, pull, 

thin, prune, 

train, tie 

5,000 0 0.7693 230 

Cane turning, 

girdle 10,000 0 1.5386 110 

Grapes 

(Table) 

(IT) 

1.4 

Hedge, irrigate, 

weed, scout, 

train, tie 

500 0 

3.141 

0.0449 3900 

Scout, train, tie 1,000 0 0.0898 1900 

Harvest, pull, 

thin, prune, 

train, tie 

5,000 0 0.4488 390 

Cane turning, 

girdle 10,000 0 0.8975 190 

Turf/ sod 

(ST) 5.2 

Mowing 500 0 

2.917 

0.042 4200 

Transplant, 

weed, harvest 6,800 0 0.567 310 

Turf/ Sod 

(IT) 0.6 

Mowing 500 0 

0.337 

0.005 36000 

Transplant, 

weed, harvest 6,800 0 0.065 2700 

Insecticide Product 

Corn (ST) 5 

Scout, weed low 

foliage 100 0 

11.219 

0.0321 5500 

Scout, weed 

high foliage 400 0 0.1282 1400 

Scout, irrigate, 

weed high 1,000 0 0.3205 550 
36 

Table 12: Short- and Intermediate-Term Occupational Post-application Dermal Exposures and Risks for MOTs

Crop & 

Exposure 

Duration 

Application 

Rate 

(lb inert /A) Work Activity 

Transfer 

Coefficient1

(cm2/hr) 

Day after 

Treatment2

DFRt

(μg/cm2)

3

Daily Dose 

(mg/kg/day)4 MOE5

foliage 

Harvesting/ 

detassling 17,000 0 5.4492 32 

Days after treatment when MOE > 100 11 

Corn (IT) 0.5 

Scout, weed low 

foliage 100 0 

1.122 

0.0032 55000 

Scout, weed 

high foliage 400 0 0.0128 14000 

Scout, irrigate, 

weed high 

foliage 

1,000 0 0.0321 5500 

Harvesting/ 

detassling 17,000 0 0.5449 320 

Grapes 

(Table) (ST) 3.5 

Hedge, irrigate, 

weed, scout, 

train, tie 

500 0 

7.853 

0.1122 1600 

Scout, train, tie 1,000 0 0.2244 780 

Harvest, pull, 

thin, prune, 

train, tie 

5,000 0 1.1219 160 

Cane turning, 

girdle 10,000 0 2.2438 78 

Days after treatment when MOE > 100 3 

Grapes 

(Table) 

(IT) 

1.5 

Hedge, irrigate, 

weed, scout, 

train, tie 

500 0 

3.366 

0.0481 3600 

Scout, train, tie 1,000 0 0.0962 1800 

Harvest, pull, 

thin, prune, 

train, tie 

5,000 0 0.4808 360 

Cane turning, 

girdle 10,000 0 0.9616 180 

Turf/ sod 

(ST) 5 

Mowing 500 0 

2.805 

0.040 4400 

Transplant, 

weed, harvest 6,800 0 0.545 320 

Turf/ Sod 

(IT) 0.5 

Mowing 500 0 

0.28 

0.004 44000 

Transplant, 

weed, harvest 6,800 0 0.054 3200 

Fungicide Products 

Corn (ST) 2.5 

Scout, weed low 

foliage 100 0 

5.609 

0.016 11000 

Scout, weed 

high foliage 400 0 0.0641 2700 

Scout, irrigate, 

weed high 

foliage 

1,000 0 0.1603 1100 

Harvesting/ 

detassling 17,000 0 2.7246 64 

Days after treatment when MOE > 100 5 
37 

Table 12: Short- and Intermediate-Term Occupational Post-application Dermal Exposures and Risks for MOTs

Crop & 

Exposure 

Duration 

Application 

Rate 

(lb inert /A) Work Activity 

Transfer 

Coefficient1

(cm2/hr) 

Day after 

Treatment2

DFRt

(μg/cm2)

3

Daily Dose 

(mg/kg/day)4 MOE5

Corn (IT) 0.5 

Scout, weed low 

foliage 100 0 

1.122 

0.0032 55000 

Scout, weed 

high foliage 400 0 0.0128 14000 

Scout, irrigate, 

weed high 

foliage 

1,000 0 0.0321 5500 

Harvesting/ 

detassling 17,000 0 0.5449 320 

Grapes 

(Table) (ST) 2.5 

Hedge, irrigate, 

weed, scout, 

train, tie 

500 0 

5.609 

0.0801 2200 

Scout, train, tie 1,000 0 0.1603 1100 

Harvest, pull, 

thin, prune, 

train, tie 

5,000 0 0.8014 220 

Cane turning, 

girdle 10,000 0 1.6027 120 

Grapes 

(Table) 

(IT) 

1 

Hedge, irrigate, 

weed, scout, 

train, tie 

500 0 

2.244 

0.0321 5500 

Scout, train, tie 1,000 0 0.0641 2700 

Harvest, pull, 

thin, prune, 

train, tie 

5,000 0 0.3205 550 

Cane turning, 

girdle 10,000 0 0.6411 270 

Turf/ sod 

(ST) 2.5 

Mowing 500 0 

1.402 

0.020 8700 

Transplant, 

weed, harvest 6,800 0 0.272 640 

Turf/ Sod 

(IT) 0.5 

Mowing 500 0 

0.28 

0.004 44000 

Transplant, 

weed, harvest 6,800 0 0.054 3200 

1 Transfer coefficient from Science Advisory Council for Exposure: Policy Memo #003 “Agricultural Transfer Coefficients” 

05/07/98. 

2 DAT = Day After Treatment 

3

 DFR = Application rate (lbs inert/acre) * fraction of active ingredient that remains on foliage (0.2 for crop, 0.05 for turf)* (1-

D(10% dissipation))(t= 0) * 4.54 μg/lb * 24.7 x10-9 acre/cm2 

4 Daily Dose = DFR (μg/cm2

) * Tc (cm2/hr) * (1 mg/1000 μg) * ET (8 hrs/day) * 25% Dermal Absorption/ body weight (70 kg) 5

 Dermal MOE = PoD (NOAEL of 175 mg/kg/day)/ Daily dermal dose (mg/kg/day). 

IX. ENVIRONMENTAL JUSTICE 

Potential areas of environmental justice concerns, to the extent possible, were considered in this 

human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions 

to Address Environmental Justice in Minority Populations and Low-Income Populations," 

http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf. 
38 

As a part of every pesticide risk assessment, OPP considers a large variety of consumer 

subgroups according to well-established procedures when applicable. In line with OPP policy, 

ARIA/HED estimates risks to population subgroups from pesticide exposures that are based on 

patterns of that subgroup’s food and water consumption, and activities in and around the home 

that involve pesticide use in a residential setting. Extensive data on food consumption patterns 

are compiled by the USDA under the Continuing Survey of Food Intakes by Individuals (CSFII) 

and are used in pesticide risk assessments for all registered food uses of a pesticide. These data 

are analyzed and categorized by subgroups based on age, season of the year, ethnic group, and 

region of the country. Additionally, OPP is able to assess dietary exposure to smaller, 

specialized subgroups and exposure assessments are performed when conditions or 

circumstances warrant. Whenever appropriate, non-dietary exposures based on home use of 

pesticide products and associated risks for adult applicators and for children (three to less than 

six years old), youths, and adults entering or playing on treated areas post-application are 

evaluated. Further considerations are currently in development as OPP has committed resources 

and expertise to the development of specialized software and models that consider exposure to 

bystanders and farm workers as well as lifestyle and traditional dietary patterns among specific 

subgroups. 

X. RISK CHARACTERIZATION 

The Agency is unaware of any current residential or pesticidal uses for AADPA chemicals. 

Acute studies revealed low acute and dermal toxicity for AADPAs, Toxicity Category III and IV, 

respectively. When tested on rabbits, the chemical was shown to be moderately irritating to the 

skin and severely irritating to the eyes. Skin sensitization studies in guinea pigs showed that 

AADPAs were not skin sensitizers. 

Several repeat dose studies were conducted on amides, C5-C9, N-[3-(dimethylamino) propyl]. A 

28-day range finding study in rats showed no evidence of toxicity at doses up to 300 mg/kg/day 

(NOAEL). Systemic toxicity (e.g., lower body weight gain and food consumption, and effects on 

red blood cells) were noted at 800 and 1000 mg/kg/day. Females in the 800 mg/kg/day group 

also had lower organ weights of the liver, spleen, and thymus. 

A second range finding study administered AADPA to female rats on gestation days 6-19. All 

females in the 1000 mg/kg/day group were found dead or euthanized in extremis by gestation 

day 8. In the 500 mg/kg/day group, two females were euthanized in extremis on gestation day 9 

or 14. Females in this group, including the two females that were euthanized in extremis, 

exhibited clinical signs of toxicity (e.g., rales, increased respiration, gasping, dilated pupils, 

salivation and body weight gains and food consumption). There were no test-substance related 

clinical findings noted up to150 mg/kg/day groups. Intrauterine growth and survival were 

unaffected by test substance administration at dose levels up to 500 mg/kg/day. No external 

malformations or developmental variations were noted in this study. The maternal and 

developmental NOAELs for this study were 150 and 500 mg/kg/day, respectively. 

A dietary combined 90-day/Reproductive and Developmental Toxicity Screening study in rats 

showed no evidence of toxicity at exposure up to 175 mg/kg/day. At the high-dose (600 
39 

mg/kg/day), systemic toxicity was exhibited by clinical findings, lower mean body weights, body 

weight gains, and food consumption for the males, toxicology phase females and reproductive 

phase females. Lower absolute and relative-to-brain ovary, uterus, and pituitary weights were 

noted for the 600 mg/kg/day reproductive phase females. In addition, lower litter size, number of 

pups born, implantation sites, and mean pup body weights were noted in the 600 mg/kg/day 

group in the presence of excessive maternal toxicity. Therefore, the systemic, reproductive, and 

developmental NOAELs were considered to be 175 mg/kg/day. This study NOAEL was chosen 

as the Toxicity Endpoint used for all exposure scenarios in this risk assessment. 

Based on the negative findings in both the mutagenicity and clastogenicity studies, the lack of 

evidence of specific target organ toxicity, and the lack of structural alerts in DEREK the Agency 

concluded that AADPAs have low potential to be carcinogenic. Functional observational battery 

(home cage, handling, open field, neuromuscular, and physiological observations) and locomotor 

activity (no remarkable shifts in the pattern of habituation) were recorded for Sprague-Dawley 

rats treated with 600 mg/kg/day of the test substance and no test related effects were observed. 

(MRID 48117116) Although evidence of neurotoxicity was observed in MRID 48117117 as 

indicated in the 500 mg/kg/day treatment group (dilated pupils) and the 1000 mg/kg/day 

treatment group (dilated pupils and clonic convulsions), these clinical signs were considered 

secondary to severe systemic toxicity and not a neurologic origin. The Point of Departure (POD) 

of 175 mg/kg/day used in this risk assessment is protective of the effects seen at these dose 

levels. 

 

The 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). DMAPA 

has been recently evaluated by the Agency and a Final Rule published in the Federal Register on 

August 5, 2009 gave DMAPA an exemption from tolerance under 40 CFR 180.920 and 180.930. 

Although there is a potential to produce the metabolite DMAPA, EPA does not anticipate any 

risk concerns from aggregate exposure to DMAPA because evidence from toxicology studies 

indicates that metabolization to DMAPA does not occur in significant amounts and the previous 

risk assessment of the metabolite DMAPA (as inert ingredient) indicates that any marginal 

increase in DMAPA exposure as a result of the use of amides, C5-C9, N-[3-(dimethylamino) 

propyl] and amides, C6-C12, N-[3-(dimethylamino) propyl] would not alter the DMAPA risk 

significantly nor change EPA’s conclusion regarding the safety of DMAPA. 

Exposure to AADPAs will be primarily through the oral route of exposure when eating food 

treated with pesticides containing the chemical. In order to estimate the exposure from oral 

exposure to AADPAs the EPA’s highly conservative I-DEEM model, which incorporates a 

default drinking water concentration of 100 ppb, was used. These chemicals are expected to bind 

tightly to soil and rapidly degrade and are therefore, unlikely to reach ground or surface water. 

The use of the I-DEEM will lead to an even more conservative estimate of exposure than what 

would be expected from the use of AADPAs as inert ingredients in pesticide formulations. They 

are unlikely to volatilize so inhalation exposure is not expected 

The I-DEEM showed the exposure from the use of this inert ingredient at 50% in formulation 

(including exposure through drinking water) would result in acceptable risk to all 
40 

subpopulations. The most highly exposed subpopulation was children 1-2 years old at 35.7% of 

the cPAD. 

Residential exposure to outdoor pesticide products were evaluated using Agency approved 

models to estimate the risk to residential handlers and post-application exposures. All exposure 

scenarios resulted in acceptable levels of risk (i.e., MOEs >100 based on 10X interspecies 

extrapolation, 10X for intraspecies variability and 1X FQPA factor) to all subpopulations 

evaluated. Exposure to AADPA inert ingredients via paint, residential antimicrobials, and pet 

products were not evaluated in this risk assessment and therefore, should not be permitted in 

pesticide formulations intended for these uses. When residential and dietary exposures were 

combined exposure did not exceed the acceptable level of risk. 

Occupational exposure models showed that the use of this inert ingredient will result in 

exposures below the Agency’s level of concern (with the use of gloves in a few occupational 

exposure scenarios). Therefore, the Agency believes there is acceptable risk from the use of 

AADPAs as inert ingredients in pesticide formulations applied to growing crops and raw 

agricultural commodities after harvest. 

XI. ECOLOGICAL EFFECTS 

Daphnia magna were exposed for 48-hours under static conditions to five mean measured 

concentrations of amides, C5-C9, N-[3-(dimethylamino) propyl] ranging from 2.9 to 48 mg/L. 

The 48-hour EC50 value was 15 mg/L with a 95% confidence interval of 12 to 17 mg/L. The 

slope of the concentration-response curve was 8.202. The no-immobility concentration and the 

NOEC were both 6.0 mg/L. This study indicates that AADPAs are slightly toxic to fresh water 

daphnids based on acute toxicity (MRID 48117105). 

A 96-hour static acute toxicity test with Rainbow Trout (Oncorhynchus mykiss) (OPPTS Test 

Guideline 850.1075) was conducted on amides, C5-C9, N-[3-(dimethylamino) propyl]. Rainbow 

trout were exposed under static conditions for 96-hours to five mean measured concentrations of 

amides, C5-C9, N-[3-(dimethylamino) propyl] ranging from 9.5 to 50 mg/L. The 96-hour LC50

value was empirically derived to be 50 mg/L with a 95% confidence interval of 34 mg/L and 

above. The no-mortality concentration and NOEC were 34 mg/L. This study indicates that 

AADPAs are slightly toxic to rainbow trout based on acute toxicity (MRID 48117106). 

An acute oral toxicity study was conducted on the Northern Bobwhite (OPPTS 850.2100) at 

doses of 0, 175, 292, 486, 810, or1350 mg/kg. The acute oral LD50 value for northern bobwhite 

was calculated to be 561 mg/kg with a 95% confidence interval of 441 to 716 mg/kg. The slope 

of the dose response curve was 5.516 with a Chi-square value of 0.704. The no-mortality level 

was 175 mg/kg. This study indicates that AADPAs are slightly toxic to Northern Bobwhite based 

on acute toxicity (MRID 48117107). 

A dietary LC50 study (OPPTS 850.2200) was conducted on the Northern Bobwhite at doses of 0, 

562, 1000, 1780, 3160 or 5620 ppm. The dietary LC50 value for Northern Bobwhite exposed to 

amides,, C5-C9, N-[3-(dimethylamino) propyl] was determined to be greater than 5620 ppm 

(1130 mg/kg/day), the highest concentration tested. The no mortality concentration was 5620 

ppm. The no observed effect concentration, based on a body weight effect at the 5620 ppm test 
41 

concentration, was 3160 ppm (623 mg/kg/day). This study indicates that AADPAs are practically 

non-toxic to Northern Bobwhite (MRID 48117108). 

Pseudokirchneriella subcapitata were exposed to seven concentrations of amides, C5-C9, N-[3-

(dimethylamino) propyl] and evaluated for effects on cell density, area under the growth curve 

(biomass) and growth rate (OPPTS 850.5400). The 96-hour EC50, based on cell density, was 

estimated to be 1.25 mg/L with a 95% confidence interval of 1.17 to 1.32 mg/L. The EbC50, 

based on area under the growth curve, was 1.15 mg/L, with the 95% confidence intervals of 1.01 

to 1.30 mg/L. The ErC50, based on growth rate, was 2.13 mg/L with the 95% confidence 

intervals of 2.08 to 2.18 mg/L. At 96-hours, Dunnett’s test indicated that cell density and growth 

rate were significantly reduced (p<0.05) in the 1.3 and 2.7 mg amides, C5-C9, N-[3-

(dimethylamino) propyl]/L treatment groups relative to the negative control. Area under the 

growth curve was significantly reduced in the 0.64, 1.3, and 2.7 mg amides, C5-C9, N-[3-

(dimethylamino) propyl]/L treatment groups when compared to the negative control. EC20

values, calculated as a 96-hour NOAEC estimate, were 0.92, 0.77, and 1.48 mg/L for cell 

density, biomass and growth rate, respectively (MRID 48117109). 

The algal species used in this study is not one of the four that is listed in the study guideline; 

therefore, the optimal concentrations or environmental conditions are not listed for this species. 

However, all the environmental factors for the study are within the range of the species that are 

mentioned in the guideline. 
42 

REFERENCES 

MRID 48117110: Oley SD (2009) Acute Oral Toxicity Up And Down Procedure In Rats. Project 

Number: 26611. Unpublished report prepared by Eurofins/Product Safety Laboratories. July 16, 

2009. 

MRID 48117111: Oley SD (2009) Acute Dermal Toxicity Study in Rats. Project Number 26612. 

Unpublished study prepared by Eurofins/Product Safety Laboratories. July 16, 2009. 

MRID 48117112: Oley SD (2009) Primary Eye Irritation Study in Rabbits. Project Number: 

26613. Unpublished study prepared by Eurofins/Product Safety Laboratories. July 16, 2009. 

MRID 48117113: Oley SD (2009) Primary Skin Irritation Study in Rabbits. Project Number 

26614. Unpublished study prepared by Eurofins/Product Safety Laboratories. July 16, 2009. 

MRID 48117114: Oley SD (2009) Dermal Sensitization Study in Guinea Pigs (Buehler Method). 

Project Number 26615. Unpublished study prepared by Eurofins/Product Safety Laboratories. 

July 17, 2009. 

MRID 48117115: Haas MC (2010) A 28-Day Oral (dietary) Dose Range Finding Study in Rats 

with MON 51803. Unpublished study prepared by WIL Research Laboratories. April 15, 2010. 

MRID 48117116: Edwards TL (2010) A dietary combined 90-day/Reproductive and 

Developmental Toxicity Screening Study of MON 51803 in rats. Unpublished study prepared by 

WIL Research Laboratories. May 20, 2010. 

MRID 48117117: Edwards TL (2010) An Oral (gavage) Range-finding Prenatal Developmental 

Toxicity Study of MON 51803 in Rats. Unpublished study prepared by WIL Research 

Laboratories. February 26, 2010. 

MRID 48117118: Farabaugh CS (2009) Bacterial Reverse Mutation Assay with a Confirmatory 

Assay. Unpublished study prepared by Covance Laboratories Inc. August 21, 2009. 

MRID 48117119: Xu Y (2009) In Vivo Mouse Bone Marrow Micronucleus Assay. Unpublished 

study prepared by Covance Laboratories Inc. August 13, 2009. 

MRID 48205701: Van Ginkel CG (2009) Biodegradability of Cross Reference 1 in the Closed 

Bottle Test. Study Number T09040C. Unpublished study prepared by Akzo Nobel Technology & 

Engineering, Arnhem, Netherlands. November 3, 2009 

MRID 48117101: Prost D (2010). Substance Characterization for MON 51803, a Surfactant to 

be used in XXX Formulations. Unpublished study prepared by Monsanto Company. June 24, 

2010. 

MRID 48117102: Walsh K (2010). Adsorption/Desorption of [14C] for MON 51803 in Five 

Soils. Unpublished study prepared by Ricerca Biosciences, LLC. June 10, 2010. 
43 

MRID 48117103: Grommes S and DiFrancesco D (2010). Hydrolysis of [14C]MON 51803 in pH 

4, pH 7 and pH 9 Buffered Water. Unpublished study prepared by Ricerca Biosciences, LLC. 

June 4, 2010. 

MRID 48117104: Herczog KJS (2010). Rate of Degradation of [14C]MON 51803 in Three Soils 

Under Aerobic Conditions. Unpublished study prepared by Ricerca Biosciences, LLC. June 4, 

2010. 

MRID 48117105: Minderhout T, Kendall TZ, and Krueger HO (2010). A 48-Hour Static Acute 

Toxicity Test with the Cladoceran (Daphnia magna). Unpublished study prepared by Wildlife 

International, Ltd. June 14, 2010. 

MRID 48117106: Minderhout T, Kendall TZ, and Krueger HO (2010). MON 51803: A 96-Hour 

Static Acute Toxicity Test with the Rainbow Trout (Oncorhynchus mykiss). Unpublished study 

prepared by Wildlife International, Ltd. June 14, 2010. 

MRID 48117107: Hubbard PM and Beavers JB (2010). MON 51803: An Acute Oral Toxicity Study 

with the Northern Bobwhite. Unpublished study prepared by Wildlife International, Ltd. May 4, 

2010. 

MRID 48117108: Hubbard PM, Martin KH, and Beavers JB (2010). MON 51803: A Dietary LC50 

Study with the Northern Bobwhite. Unpublished study prepared by Wildlife International, Ltd. May 4, 

2010. 

MRID 48117109: Cartee TL, Kendall TZ, Krueger HO, and Porch JR(2010). MON 51803: A 96-

Hour Toxicity Test with the Freshwater Alga (Pseudokirchneriella subcapitata). Unpublished study 

prepared by Wildlife International, Ltd. June 9, 2010.

US Environmental Protection Agency (2011) Occupational Pesticide Handler Unit Exposure 

Surrogate Reference Table. (May 4, 2011) retrieved from 

http://www.epa.gov/pesticides/science/handler-exposure-table.pdf
44 

Appendix A 

U.S. Environmental Protection Agency Ver. 2.00 

DEEM-FCID Chronic analysis for INERTS (1994-98 data) 

Residue file name: C:\DEEMFCID\Inerts_57active_100ppbH2Orev.R98 

 Adjustment factor #2 NOT used. 

Analysis Date 03-17-2011/12:04:37 Residue file dated: 03-03-2009/12:17:18/8 

Reference dose (RfD, Chronic) = 1.75 mg/kg bw/day 

NOEL (Chronic) = 175 mg/kg bw/day 

COMMENT 1: Inert 57 active ingredients + drinking water (100ppb) 

=============================================================================== 

 Total exposure by population subgroup 

------------------------------------------------------------------------------- 

 Total Exposure 

 ----------------------------------- 

 Population mg/kg Margin of Percent 

 Subgroup body wt/day Exposure 1/ of RfD 

-------------------------------------- ------------- ---------- --------- 

U.S. Population (total) 0.191509 914 10.9% 

U.S. Population (spring season) 0.195512 895 11.2% 

U.S. Population (summer season) 0.193733 903 11.1% 

U.S. Population (autumn season) 0.188144 930 10.8% 

U.S. Population (winter season) 0.188739 927 10.8% 

Northeast region 0.208249 840 11.9% 

Midwest region 0.190460 919 10.9% 

Southern region 0.171478 1,021 9.8% 

Western region 0.209414 836 12.0% 

Hispanics 0.201698 868 11.5% 

Non-hispanic whites 0.187723 932 10.7% 

Non-hispanic blacks 0.185288 944 10.6% 

Non-hisp/non-white/non-black 0.246967 709 14.1% 

All infants (< 1 year) 0.397082 441 22.7% 

Nursing infants 0.212711 823 12.2% 

Non-nursing infants 0.467077 375 26.7% 

Children 1-6 yrs 0.495834 353 28.3% 

Children 7-12 yrs 0.239839 730 13.7% 

Females 13-19 (not preg or nursing) 0.138939 1,260 7.9% 

Females 20+ (not preg or nursing) 0.149292 1,172 8.5% 

Females 13-50 yrs 0.154523 1,133 8.8% 

Females 13+ (preg/not nursing) 0.163842 1,068 9.4% 

Females 13+ (nursing) 0.192592 909 11.0% 

Males 13-19 yrs 0.148194 1,181 8.5% 

Males 20+ yrs 0.144142 1,214 8.2% 

Seniors 55+ 0.152430 1,148 8.7% 

Children 1-2 yrs 0.624005 280 35.7% 

Children 3-5 yrs 0.461958 379 26.4% 

Children 6-12 yrs 0.255310 685 14.6% 

Youth 13-19 yrs 0.144122 1,214 8.2% 

Adults 20-49 yrs 0.144401 1,212 8.3% 

Adults 50+ yrs 0.152076 1,151 8.7% 

Females 13-49 yrs 0.145389 1,204 8.3% 

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