EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR 

PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER 

EPA Registration Division contact: [PV Shah, Branch Chief Inert Assessment 

Branch (IAB) 703-308-1846]

INSTRUCTIONS: Please utilize this outline in preparing the pesticide petition. In 

cases where the outline element does not apply, please insert “NA-Remove” and 

maintain the outline. Please do not change the margins, font, or format in your 

pesticide petition. Simply replace the instructions that appear in green, i.e., “BASF 

Corporation,” with the information specific to your action.

TEMPLATE:

BASF Corporation

[TBD]

EPA has received a pesticide petition ([TBD]) from [Spring Trading Company, 

LLC on behalf of BASF Corporation, 100 Campus Drive, Florham Park, NJ 07932,

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

(FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180.910 and 930.

The addition of an exemption from the requirement of a tolerance for Propanamide, 2-

hydroxy-N, N-dimethyl- (9CI) as a solvent/co-solvent in or on the raw agricultural 

commodity [growing crops or in products to treat animals] at [under 40 CFR 

180.910, and 930]. EPA has determined that the petition contains data or information 

regarding the elements set forth in section 408 (d) (2) of FDDCA; however, EPA has not 

fully evaluated the sufficiency of the submitted data at this time or whether the data 

supports granting of the petition. Additional data may be needed before EPA rules on the 

petition.

A. Residue Chemistry

[The petitioner has provided EPA with sufficient toxicity data to support the 

issuance of this tolerance exemption for an inert ingredient. The data submitted 

will allow EPA to determine the sensitivities of major identifiable subgroups of 

consumers, including infants and children.]
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1. Analytical method. [An analytical method is not required for enforcement 

purposes since the Agency is establishing an exemption from the requirement of a 

tolerance without any numerical limitation.]

2. Magnitude of residues. [BASF Corporation is petitioning the agency to 

establish an exemption from the requirement of a tolerance for a class of chemistry 

that is well known and similar to an existing tolerance exemption. Therefore 

information regarding the nature and magnitude of chemical residues resulting 

from the use of this inert ingredient is not required.]

B. Toxicological Profile

1. Acute toxicity.

Oral: [Two groups, each of three female HanRcc: WIST (SPF) rats, were treated 

with Propanamide, 2-hydroxy-N, N-dimethyl- (9CI) by oral gavage administration 

at a dos of 2000 mg/kg body weight. The test item was diluted in vehicle (purified 

water) to a concentration of 0.5 g/mL and administered at a dosing volume of 4 

mL/kg. The animals were examined daily during the acclimatization period and 

mortality, viability and clinical signs were recorded. All animals were examined for 

clinical signs at approximately 30 minutes, 1, 2, 3 and 5 hours after treatment on 

day 1 and once daily during test days 2-15. Mortality/viability was recorded at 

approximately 30 minutes, 1, 2, 3 and 5 hours after administration on test day 1 

(with the clinical signs) and twice daily during days 2-15. Body weights were 

recorded on day 1 (prior to administration) and on days 8 and 15. All animals were 

necropsied and examined macroscopically. All animals survived until the end of the 

study period. No clinical signs were observed during the course of the study. The 

body weight of the animals was within the range commonly recorded for this strain 

and age. No macroscopic findings were recorded at necropsy. The oral LD50 in the 

rat was greater than 2000 mg/kg body weight (Toxicity Category III).]

Dermal: Five male and five female HanRcc: WIST (SPF) rats were treated with 

Propanamide, 2-hydroxy-N, N-dimethyl- (9CI) at 2000 mg/kg by dermal 

application. The OECD testing guideline 402. The test item was diluted in vehicle 

(purified water) at a concentration of 0.5 g/mL and administered at a volume dosage 

of 4 mL/kg. The application period was 24 hours. The animals were examined daily 

during the acclimatization period and mortality, viability and clinical signs were 

recorded. All animals were examined for clinical signs at approximately 30 minutes, 

1, 2, 3 and 5 hours after treatment on day 1 and once daily during test days 2-15. 

Local signs were noted once daily from test day 2 to 15. Mortality/viability was 

recorded at approximately 30 minutes, 1, 2, 3 and 5 hours after administration on 

test day 1 (with the clinical signs) and twice daily during days 2-15. Body weights

were recorded on day 1 (prior to administration) and on days 8 and 15. All animals 

were necropsied and examined macroscopically. No deaths occurred during the 

study. No clinical signs of systemic toxicity were observed during the course of the 

study. Local findings were noted at the application site of all animals except one 

female. These comprised slight erythema, slight scaling and slight to moderate scab 

formation. At the end of the two-week observation period, local findings were still 
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present in one male and four female animals. The body weight of the animals was 

within the range commonly recorded for this strain and age. No macroscopic 

findings were observed at necropsy. The dermal LD50 was >2000 mg/kg (Toxicity 

Category III).

Inhalation: HanRCC:WIST (SPF) (5/sex) were exposed by nose only to 

Propanamide, 2-hydroxy-N, N-dimethyl- (9CI) at a mean chemically determined 

concentration of 5.005 mg/L for a period of four hours. The gravimetrically 

determined concentration was 5.226 mg/L. The study was conducted according to 

OECD test guideline 403 and OPPTS test guideline 870.1300. The rats were 

examined at 1, 2, 3 and 4 hours after the start of exposure, approximately 1 and 2.5 

hours after exposure on day 1 and at least twice daily during the 14-day observation 

period. Clinical signs were recorded at approximately 1, 2, 3 and 4 hours after the 

start of exposure, at approximately 1 hour at the end of exposure and then daily to 

study termination. Body weights were recorded on study days 1, 4, 8 and 15. A

complete necropsy was conducted at the end of exposure. There were no deaths, 

clinical signs of toxicity or gross necropsy findings. A body weight loss was noted in 

some of the rats. Particle size was determined twice and was 2.52 and 2.32 μm with 

a GSD of 1.93 and 2.15, respectively. The acute inhalation LC50 was determined to 

be >5.005 mg/L (Toxicity Category IV).

Eye Irritation: Propanamide, 2-hydroxy-N, N-dimethyl- (9CI) was tested for eye 

irritation potential in the eyes of three young adult New Zealand white rabbits 

according to OECD test guideline 405. One tenth of an mL of the test substance was 

to the left eye of one male and two females. The right eye served as the control. The 

eyes of each animal were examined 1, 24, 48, and 72 after administering the test 

material. No corneal opacity or iritis was observed. Redness (3 rabbit; score = 2) 

and chemises (2 rabbits; score = 2) of the conjunctiva was observed at 1 hour. The 

eyes were clear at 72 hours. No clinical signs of systemic toxicity were observed 

during the study and no mortality occurred. This product is considered to be 

“mildly irritating” to the rabbit eye (Toxicity Category III). The study authors 

concluded that the test material was “not irritating” to the rabbit eye.

Dermal Irritation: Propanamide, 2-hydroxy-N, N-dimethyl- (9CI) was tested for 

dermal irritation according to OECD test guideline 404. The test material (0.5 mL0 

was applied to a gauze patch and placed on the clipped intact skin of the left flank of 

one male and two female New Zealand white rabbits. The patch was covered with a 

semi-occlusive dressing. The dressing was wrapped around the abdomen and 

secured with tape. Animals were observed for mortality and clinical signs daily 

during acclimation and throughout the test. Body weights were recorded at the 

start of acclimation, on the day of application and study termination. The test sites 

were scored for dermal irritation at 1, 24, 48 and 72 hours after removal of the 

dressing and gauze patch. No mortality or clinical signs of toxicity occurred. The 

only irritation observed occurred in one female rabbit at 1 hour after exposure. 

This animal had erythema with a score of 1. It had cleared by 24 hours. The test 

material was considered to be “not irritating” to rabbit skin (Toxicity Category IV).
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Dermal Sensitization: Propanamide, 2-hydroxy-N, N-dimethyl- (9CI) was tested for 

possible skin sensitization potential using the local lymph node assay in mice. Three 

groups of four females CBA/CaOlaHd mice were treated daily with the test item at 

concentrations of 25, 50, and 100% (w/v) for three consecutive days, and a separate 

control group of four female mice were treated with the vehicle only. The 

application volume, 25 μl, was spread over the entire dorsal surface ( ̴ 8mm) of each 

ear lobe once daily for three consecutive days. Five days after the first topical 

application the mice were injected intravenously into a tail vein with radio-labelled 

thymidine (3H-methyl thymidine). The proliferative capacity of pooled lymph node 

cells was determined by the incorporation of 3H-methyl thymidine measured in a βscintillation counter. A positive response was considered to be a Stimulation Index 

of >3. No mortality or clinical signs of toxicity was observed. The Stimulation 

Indices were 1.6, 1.8 and 2.4 at concentrations of 25, 50 and 100%, respectively. This 

product was found not to be a skin sensitizer under the conditions of this study.

2. Genotoxicty. [Propanamide, 2-hydroxy-N, N-dimethyl- (9CI) does not react 

with DNA or protein, and bacterial mutagenicity studies do not indicate a concern 

for mutagenicity. Based on the lack of genotoxicity and lack of specific organ 

toxicity in the repeated dose studies, carcinogenic effects are unknown.

Propanamide, 2-hydroxy-N, N-dimethyl- (9CI) shows no evidence of mutagenicity, 

(AMES).]

3. Reproductive and developmental toxicity. Several developmental toxicity 

studies were located on Propanamide, 2-hydroxy-N, N-dimethyl- (9CI) and its 

effects on the prenatal development in Wistar rats. Propanamide, 2-hydroxy-N, Ndimethyl- (9CI) was tested for developmental toxicity in Wistar rats. The test 

substance was administered as an aqueous solution to groups of 25 time-mated 

female Wistar rats by gavage at doses of 100, 200, and 500 mg/kg body weight/day 

(mg/kg bw/d) on gestation days (GD) 6 through 19. A standard dose volume of 10 

mL/kg body weight was used for each test group.

The NOAELs for maternal and developmental toxicity were as follows:

 Propanamide, 2-hydroxy-N, N-dimethyl- (9CI): 

 500 mg/kg/day (highest dose tested; HDT) for maternal and developmental 

toxicity in female rats

 200 mg/kg/day (HDT) for maternal and developmental toxicity in female rats

 100 mg/kg/day (HDT) for maternal and developmental toxicity in female rats

4. Subchronic toxicity. [Wistar rats (10/sex/group) were administered 

Propanamide, 2-hydroxy-N, N-dimethyl- (9CI) by gavage at dose levels of 0, 100, 

200, 500 and 1000 mg/kg/day for 90 days. The study was conducted according to 

OECD test guideline 408. The animals were observed for mortality twice daily and 

for clinical signs of toxicity daily and within 2 to 5 hours of dose administration. 

Detailed clinical examinations were conducted weekly. Body weights and food 

consumption were recorded weekly. A functional observation battery was 

performed on all animals at the end of the exposure period. Motor activity was 
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measured the same day as the FOB was conducted. Ophthalmology was performed 

prior to dose administration and on study day 91 for males and study day 89 for 

females. Vaginal smears were taken daily for three weeks to determine estrus 

cycling. Blood was taken from fasted animals for hematology and clinical chemistry 

evaluations. Urinalysis parameters were examined at study termination. The 

following sperm parameters were evaluated: sperm motility, sperm morphology 

and sperm head count (cauda epididymis and testis. A complete necropsy was 

performed and a full set of organs were weighed and examined microscopically.

There were no deaths during the study. Food consumption, FOB observations, 

motor activity, urinalysis parameters, ophthalmology, sperm parameters and 

estrous cyclicity were unaffected by treatment. Body weight gain was statistically 

decreased in males at 1000 mg/kg/day. Platelet counts and relative eosinophil counts 

were statistically decreased at the high dose in females. Cholesterol levels were 

statistically increased in males and females at the high dose and in males at 500 

mg/kg/day. Creatinine levels were statistically decreased in both sexes at 500 and 

1000 mg/kg/day. Triglyceride levels were statistically increased in males at 500 and 

1000 mg/kg/day. Absolute and relative liver weights were statistically increased in 

males at 500 and 1000 mg/kg/day and relative liver weights in females at 1000 

mg/kg/day which were accompanied with an increase in centrilobular hypertrophy. 

Relative liver weights were also, but statistically increased at 200 mg/kg/day. 

Absolute kidney weights were statistically increased in females at 200, 500 and 1000 

mg/kg/day and relative kidney weights at 1000 mg/kg/day. Relative kidney weights 

were statistically increased in males at 500 and 1000 mg/kg/day. Grade 3 

eosinophilic droplets were observed in the kidneys of the males at 500 and 1000 

mg/kg/day. The kidney effects in males were considered to be related to alpha-2uglobulin and were therefore considered treatment related but not adverse. The 

effect on kidney weight in females was not considered adverse because it was not 

accompanied with any histopathological findings. The liver effects observed at 100 

and 200 mg/kg/day were considered to be adaptive. The NOAEL was therefore 

considered to be 200 mg/kg/day and the LOAEL 500 mg/kg/day.

5. Endocrine disruption. [There is no available evidence that Propanamide, 2-

hydroxy-N, N-dimethyl- (9CI) is an endocrine disruptor. The literature was 

searched for any information on the endocrine disruption of the solvent/ co-solvent. 

No information was located indicating any potential for endocrine disruption nor 

was any evidence observed in the studies supporting this petition.]

C. Aggregate Exposure

1. Dietary exposure. [In examining aggregate exposure, section 408 of the 

FFDCA directs EPA to consider available information concerning exposures from 

the pesticide residue in food and all other non-occupational exposures, including

drinking water from ground water or surface water and exposure through pesticide 

use in gardens, lawns, or buildings (residential and other indoor uses).

EPA establishes exemptions from the requirement of a tolerance only in those cases 
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where it can be demonstrated that the risks from aggregate exposure to pesticide 

chemical residues under reasonably foreseeable circumstances will pose no 

appreciable risks to human health. In order to determine the risks from aggregate 

exposure to pesticide inert ingredients, the Agency considers the toxicity of the inert 

in conjunction with possible exposure to residues of the inert ingredient through 

food, drinking water, and through other exposures that occur as a result of pesticide 

use in residential settings. If EPA is able to determine that a finite tolerance is not 

necessary to ensure that there is a reasonable certainty that no harm will result 

from aggregate exposure to the inert ingredient, an exemption from the requirement 

of a tolerance may be established.

Propanamide, 2-hydroxy-N, N-dimethyl- (9CI) as a food ingredient that is consumed

and result in intermediate-term residential exposure and BASF has determined that 

it is appropriate to aggregate chronic exposure through food and water with 

intermediate-term residential exposures to this solvent/ co-solvent.

D. Cumulative Effects

[Cumulative effects from substances with a common mechanism of toxicity. 

Section 408(b)(2)(D)(v) of FFDCA requires that, when considering whether to 

establish, modify, or revoke a tolerance, the Agency consider “available 

information” concerning the cumulative effects of a particular pesticide's residues 

and “other substances that have a common mechanism of toxicity. BASF 

Corporation has not found that Propanamide, 2-hydroxy-N, N-dimethyl- (9CI) 

share a common mechanism of toxicity with any other substances, and 

Propanamide, 2-hydroxy-N, N-dimethyl- (9CI) does not appear to produce a toxic 

metabolite produced by other substances. For the purposes of this tolerance action, 

therefore, BASF Corporation has assumed that Propanamide, 2-hydroxy-N, Ndimethyl- (9CI) does not have a common mechanism of toxicity with other 

substances.]

E. Safety Determination

1. U.S. population. [Based on these risk assessments, BASF concludes that 

there is a reasonable certainty that no harm will result to the general population or 

to infants and children from aggregate exposure to residues of Propanamide, 2-

hydroxy-N, N-dimethyl- (9CI).]

2. Infants and children. [Based on these risk assessments, BASF concludes that 

there is a reasonable certainty that no harm will result to the general population or 

to infants and children from aggregate exposure to residues of the lower weight of

Propanamide, 2-hydroxy-N, N-dimethyl- (9CI).]

F. International Tolerances
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[BASF Corporation is not aware of any country requiring a tolerance for the

Propanamide, 2-hydroxy-N, N-dimethyl- (9CI) nor have any CODEX Maximum

Residue Levels been established for any food crops at this time.