2

Table of Contents

EXECUTIVE SUMMARY ......................................................................................................................3

I. BACKGROUND ..................................................................................................................................................8

II. INERT INGREDIENT PROFILE ........................................................................................................................8

III. HUMAN HEALTH ASSESSMENT................................................................................................................9

A. Summary of Toxicity Data................................................................................................................9

B. Toxicity Endpoint Selection............................................................................................................16

C. Special Considerations for Infants and Children...............................................................................17

IV. EXPOSURE ASSESSMENT.........................................................................................................................18

A. Dietary Exposure: ...........................................................................................................................18

i. Acute exposure ................................................................................................................................18

ii. Chronic exposure ............................................................................................................................18

iii. Cancer exposure ............................................................................................................................20

B. Residential Exposure ......................................................................................................................20

C. Residential Post-Application Exposure ..........................................................................................23

V. AGGREGATE RISK AND DETERMINATION OF SAFETY....................................................................27

A. Acute Dietary Risk.............................................................................................................................27

B. Chronic Dietary Risk..........................................................................................................................27

C. Aggregate Cancer Risk for U.S. Population.......................................................................................27

D. Short-Term Aggregate Risk ...............................................................................................................27

E. Intermediate-Term Aggregate Risk....................................................................................................28

F. Determination of Safety......................................................................................................................28

VI. OCCUPATIONAL EXPOSURE/RISK PATHWAY.....................................................................................28

A. Occupational Handler Risk .............................................................................................................29

B. Occupational Post-Application Risk...............................................................................................30

VII. CUMULATIVE EXPSOURE ........................................................................................................................31

VIII. ENVIRONMENTAL JUSTICE STATEMENT ........................................................................................31

IX. ENVIRONMENTAL FATE CONSIDERATIONS .......................................................................................32

X. ECOTOXICITY..................................................................................................................................................33

XI. RISK CHARACTERIZATION......................................................................................................................34

REFERENCES ............................................................................................................................................................40
3

EXECUTIVE SUMMARY

Wagner Regulatory Associates (7217 Lancaster Pike, Suite A. Hockessin, DE 19707) on 

behalf of Nichino America, Inc. (4550 New Linden Hill Road, Suite 501, Wilmington, DE 

19808) is requesting that EPA expand the current N-(n-octyl)-2-pyrrolidone (NOP) tolerance 

exemption. N-(n-octyl)-2-pyrrolidone (CAS Reg. No. 2687-94-7) is currently approved for an

inert ingredient tolerance exemption listed in 40 CFR 180.1130 when used as a solvent in cotton 

defoliant formulations containing thidiazuron and diuron as active ingredients. Wagner 

Regulatory Associates requested that EPA expand it to include use as an inert ingredient 

(solvent) in formulations of pyraflufen-ethyl herbicide at a maximum concentration of 20% 

weight/weight.

N-(n-octyl)-2-pyrrolidone has low acute toxicity. The acute oral LD50 = 2,050 mg/kg for 

rats (Toxicity Category III). The acute dermal LD50 > 2,000 mg/kg in rabbits (Toxicity category 

III). A primary skin irritation study on rabbits showed that N-(n-octyl)-2-pyrrolidone is 

extremely irritating. The dermal sensitization study on guinea pigs was considered positive. No 

acute inhalation study was available in the database.

There were three subchronic oral toxicity studies available in the database. A 28-day oral 

toxicity study in rats showed changes in general health, reduction in body weight gain and 

changes in hematological and biochemical parameters following treatment with 320 mg/kg/day, 

the highest dose tested, of N-(n-octyl)-2-pyrrolidone. The NOAEL = 55 mg/kg/day. In a 90-day 

oral toxicity study in rats signs of systemic toxicity, reduced body weight gain and/or food 

consumption, increase absolute and relative liver weights and minimal to mild hepatocyte 

hypertrophy were observed at 6000 ppm, the highest dose tested. The NOAEL was 600 ppm (53 

mg/kg/day). In a 90-day oral toxicity study in dogs, a dose-related increase in both absolute and 

relative liver weights, neurological signs and body weight loss were observed at 90 mg/kg/day. 

The NOAEL was 30 mg/kg/day. 

There were three mutagenicity and genotoxicity studies available in the database for N-

(n-octyl)-2-pyrrolidone. An Ames test, a mouse lymphoma mutagenesis assay and a mouse 

micronucleus test were negative for mutagenicity and genotoxicity. 

No carcinogenicity studies were available in the database for N-(n-octyl)-2-pyrrolidone.

The Agency used a qualitative structure activity relationship (SAR) database, DEREK11, to 

determine if there were structural alerts for potential carcinogenicity of for N-(n-octyl)-2-

pyrrolidone. No structural alerts for carcinogenicity were identified for N-(n-octyl)-2-

pyrrolidone. In the absence of any structural alerts and lack of mutagenicity concerns, N-(noctyl)-2-pyrrolidone is not expected to be carcinogenic.

There was one developmental toxicity study for N-(n-octyl)-2-pyrrolidone performed on 

rats, which were dosed at 0, 50, 200 and 800 mg/kg bw/day. The maternal NOAEL was 

determined to be 200 mg/kg bw/day and the maternal LOAEL was 800 mg/kg bw/day based on 

ruffled fur, ventral recumbency, somnolence, apathy, dyspnea and comatose state. Other adverse 

effects observed were a reduction in food consumption and slight body weight loss during the 
4

first days of dosing and reduced corrected body weight gain. The developmental NOAEL was 

200 mg/kg and the developmental LOAEL was 800 mg/kg based on statistically significantly 

reduced body weight and delay in skeletal ossification correlated with the severe maternal 

toxicity observed at this dosage. 

There were no reproductive toxicity studies for N-(n-octyl)-2-pyrrolidone. While there 

are no reproductive, neurotoxicity and chronic toxicity studies for N-(n-octyl)-2-pyrrolidone, 

there is no evidence of effects on reproductive parameters or of any effects suggestive of 

neurotoxicity from the available subchronic studies. 

No immunotoxicity or neurotoxicity studies were available in the database for N-(noctyl)-2-pyrrolidone.

No metabolism or pharmacokinetic studies were available in the database for N-(n-octyl)-

2-pyrrolidone.

Section 408 of the Federal Food, Drug and Cosmetic Act (FFDCA) provides that EPA 

shall apply an additional margin of safety for infants and children in the case of threshold effects 

to account for prenatal and post natal toxicity and the completeness of the database on toxicity 

and exposure unless EPA determines that a different margin of safety will be safe for infants and 

children. EPA concludes that the FQPA safety factor could be reduced from 10X to 3X for N-(noctyl)-2-pyrrolidone based on lack of increased susceptibility of infants and children from 

exposures to N-(n-octly)-2-pyrrolidone, lack of neurotoxicity and immunotoxicity concerns and 

completeness of the database for risk assessment purpose.

An acute toxicity endpoint was not established because no endpoint of concern following 

a single exposure was identified in the available studies. A toxicity endpoint for chronic dietary 

assessment and inhalation and dermal exposure assessment was selected at 30 mg/kg/day based 

on the 90-day toxicity study in dogs. This was based on changes in clinical pathological 

parameters (decrease in A/G ratio and increase in alkaline phosphatase and globulin and decrease 

in RBC, Hgb, Hct, albumin, and GGT) and statistically significant dose-related increases in both 

absolute and relative liver weights at the LOAEL of 90 mg/kg/day. An uncertainty factor 300 

was for inter-species extrapolation (10X), intra-individual variability (10X) and FQPA safety 

factor (3X). 

An acute dietary risk assessment was not conducted because no endpoint of concern 

following a single exposure was identified in the available studies. 

A chronic dietary risk assessment was conducted using the endpoint from the 90-day dog 

study. Based on the analysis of estimated dietary risks for the total U.S. population and various 

population subgroups, the chronic dietary exposure estimates for N-(n-octyl)-2-pyrrolidone are 

below the Agency’s level of concern for all supported commodities with active pyraflufen ethyl 

registrations. The chronic dietary exposure estimates for the total U.S. population is 14.3% and 

the highest exposed population subgroup, children 1-2 years old, is 59.4% of the chronic 

population adjusted dose (cPAD).
5

A cancer dietary exposure assessment was not conducted because the Agency has not 

identified a cancer risk for N-(n-octyl)-2-pyrrolidone. 

The term “residential exposure” is used in this document to refer to non-occupational, 

non-dietary exposure (e.g., for lawn and garden pest control, indoor pest control, termiticides, 

and flea and tick control on pets). N-(n-octyl)-2-pyrrolidone may be used in inert ingredients in 

pesticide products that are registered for specific uses that may result in outdoor residential 

exposures. Based on the use pattern of the active ingredient which includes but is not limited to 

golf courses, ornamental turf lawns, roadside, parks and sports fields, the major route of 

exposure is expected to be inhalation and dermal exposure. A screening level residential 

exposure and risk assessment was completed for a representative sample product containing 

pyraflufen ethyl. The 20% limit of formulation for N-(n-octyl)-2-pyrrolidone and total 

application rate of 0.0163 lbs of inert ingredient per half acre was used for risk assessment.

For residential applicator exposure, three use scenarios were used based on the sample 

label, manually pressurized hand-wand, backpack sprayer and hose-end sprayer. The Margins of 

Exposures (MOEs) were calculated to be 51000, 25000 and 11000 respectively. The acceptable 

MOE is for N-(n-octyl)-2-pyrrolidone is 300 or above; therefore these scenarios do not exceed 

the Agency’s level of concern.

For residential post-application exposure, adults and toddlers were assessed separately as 

well as a golfer scenario. The adult contact consists of dermal post-application contact with turf 

while the toddler scenarios include oral hand to mouth, incidental oral ingestion, oral object to 

mouth and dermal turf contact. The resulting MOEs were 2420 for adults and 686 for a total 

toddler combined exposure for all the scenarios. The acceptable MOE for N-(n-octyl)-2-

pyrrolidone is 300 or above; therefore residential post-application exposures do not exceed the 

Agency’s level of concern for N-(n-octyl)-2-pyrrolidone. 

Short-term residential aggregate exposure takes into account short-term residential 

exposure plus chronic exposure to food and water (considered to be a background exposure 

level). N-(n-octyl)-2-pyrrolidone is used as an inert ingredient in some pesticide products that are 

currently registered for uses that could result in short-term residential exposure. The adult shortterm aggregate MOE was calculated to be 1122 and the toddler aggregate MOE to be 291. 

Registration Division’s levels of concern are for MOEs that are less than 300, therefore the 

aggregate exposure MOE are not of concern. 

Occupational exposure scenarios selected by the Agency for assessment are evaluated 

based on likely maximum application rates for products which may contain the inert ingredient. 

The example label and the same application rates were used for the intermediate- and long-term 

exposure durations. Active ingredient application rates are corrected for the maximum amount 

of inert ingredient (20% limit) present in the final formulations to determine exposure and risk 

from exposure to the inert ingredient. The acceptable MOE for N-(n-octyl)-2-pyrrolidone is set 

at 300 or above for occupational exposure assessment. Based on the sample label, the 

occupational exposure scenarios for ground applicators and for mixer/loaders preparing and 

applying liquid formulations were used. These are the occupational activities believed to be 

associated with the highest exposures relative to the proposed label use patterns. Due to the lack 
6

of data to the contrary, dermal absorption is assumed to be 100%. The inhalation toxicity and 

dermal toxicity was also assumed to be equivalent to oral toxicity. Risks were calculated using 

the MOE approach, which is a ratio of the exposure to the toxicological point of departure (PoD). 

Occupational handler risks consisted of MOEs ranging from 4,200 to 4,200,000 and are 

considered not of concern. The Agency’s level of concern for occupational inhalation and dermal 

exposure for N-(n-octyl)-2-pyrrolidone is for MOEs <300.

Occupational post-application exposure is used to describe exposures that occur when 

individuals are present in an environment that has been previously treated with a pesticide (also 

referred to as re-entry 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. This assessment is considered to be a screening level 

assessment, demonstrating that there are minimal potential risks to workers re-entering fields 

treated with pesticides containing N-(n-octyl)-2-pyrrolidone as inert ingredients. Therefore an 

occupational post-application risk assessment was not performed. 

EPA has not found N-(n-octyl)-2-pyrrolidone to share a common mechanism of toxicity 

with any other substances, and that N-(n-octyl)-2-pyrrolidone does not appear to produce a toxic 

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

EPA has assumed that N-(-n-octyl)-2-pyrrolidone does not have a common mechanism of 

toxicity with other substances.

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.

Environmental fate data for N-(n-octyl)-2-pyrrolidone could not be found in the 

publically available scientific literature. The EPI (Estimation Programs Interface) SuiteTM

was 

used to model possible environmental fate properties of the N-(n-octyl)-2-pyrrolidone. Based on 

the estimated modeling programs, N-(n-octyl)-2-pyrrolidone is believed to be readily 

biodegradable. Also based on the modeling, N-(n-octyl)-2-pyrrolidone is estimated to have a Log 

Kow of 3.33 which can be assumed to be only slightly mobile in soils when converted to Log 

Koc. With primary biodegradation estimated to be days and ultimate biodegradation to occur in 

weeks, N-(n-octyl)-2-pyrrolidone is not expected to be very persistent in the environment and is 

therefore considered not of concern. The estimated Bioconcentration factor (BCF) is 73.29 which 

is also not expected to be of a concern 

The Ecological Structure Activity Relationships (ECOSAR) Class Program was used to 

estimate the aquatic toxicity of industrial chemicals. However study citations were also provided 

from both BASF and ISP MSDS. The ECOSAR predictions were reasonably close when 

compared with the experimental test results from BASF MSDS and the ISP MSDS. Based on the 

studies mentioned in the BASF and ISP MSDS it can be assumed that N-(n-octyl)-2-pyrrolidone 

is slightly toxic to aquatic fish on an acute basis. Also it can be assumed that N-(n-octyl)-2-

pyrrolidone is slightly toxic to aquatic invertebrates on an acute basis. N-(n-octyl)-2-pyrrolidone 

is also slightly toxic to bobwhite quail on an acute basis. It is practically non-toxic to bobwhite 
7

quail on a chronic basis based on the dietary LC50. Overall N-(n-octyl)-2-pyrrolidone is not 

expected to be of great concern with respect to ecotoxicity. 

Taking into consideration all available information on N-(n-octyl)-2-pyrrolidone, EPA 

concludes that there is a reasonable certainty that no harm to any population subgroup will result 

from aggregate exposure to N-(n-octyl)-2-pyrrolidone when considering occupational, dietary 

exposure and all other nonoccupational sources of pesticide exposure for which there is reliable 

information. Therefore, the amendment of an exemption from tolerance under 40 CFR 180.1130 

for N-(n-octyl)-2-pyrrolidone (CAS Reg. No. 2687-94-7) when used as a pesticide inert 

ingredient solvent in formulations of pyraflufen ethyl herbicide at a maximum concentration of 

20% weight/weight can be considered safe under section 408(q) of the FFDCA.
8

I. BACKGROUND

Wagner Regulatory Associates (7217 Lancaster Pike, Suite A. Hockessin, DE 19707) on 

behalf of Nichino America, Inc. (4550 New Linden Hill Road, Suite 501, Wilmington, DE 

19808) is requesting that EPA expand the current N-(n-octyl)-2-pyrrolidone (NOP) tolerance 

exemption. N-(n-octyl)-2-pyrrolidone (CAS Reg. No. 2687-94-7) is already approved for inert 

ingredient tolerance exemption listed in 40 CFR 180.1130 when used as a solvent in cotton 

defoliant formulations containing thidiazuron and diuron as active ingredients. Wagner 

Regulatory Associates requested that EPA expand it to include use as an inert ingredient solvent 

in formulations of pyraflufen ethyl herbicide at a maximum concentration of 20% weight/weight.

The information presented in this document is summarized primarily from the EPA Inert 

Reassessment: Two Exemptions from the Requirement of a Tolerance for N-(n-dodecyl)-2-

pyrrolidone (CAS Reg. No. 2687-96-9) and N-(n-octyl)-2-pyrrolidone (CAS Reg. No. 2687-94-

7) as well as the included MRIDs and subsequent Data Evaluation Records (DERs).

In the Federal Register of June 22, 1994 (59 FR 32083), EPA issued a final rule 

establishing two exemptions from the requirement of a tolerance for N-(n-dodecyl)-2-

pyrrolidone and N-(n-octyl)-2-pyrrolidone for its use as an inert ingredient solvent in cotton 

defoliant formulations containing thidiazuron and diuron as active ingredients. However the final 

rule was published prior to the enactment of FQPA, and in June 2006 an Inert Reassessment was 

performed and new data are available.

II. INERT INGREDIENT PROFILE

A. Summary of Uses

N-(n-octyl)-2-pyrrolidone is used in electronics and agrochemicals. It is used as a solvent 

in industrial chemicals, or as a chemical intermediate. It is also used as an inert ingredient 

(solvent) in cotton defoliants containing thidiazuron and diuron as active ingredients. 

B. Physical Chemical Properties

Some of the physical and chemical characteristics of N-(n-octyl)-2-pyrrolidone, along 

with its structure and nomenclature, are found in Table 1.
9

Table 1. Physical and Chemical Properties of N-(n-octyl)-2-pyrrolidone

Parameter Value Source

Structure Sigma-Aldrich MSDS

CAS # 2687-94-7

Molecular Weight (g/mol) 197.3

Common Names

NOP

1-Octyl-2-pyrrolidone

1-Octylpyrrolidon-2

1-Octyl-2-pyrrolidone

N-Octylpyrrolidone

Octylpyrrolidone

Physical State liquid BASF MSDS

Odor Amine-like BASF MSDS

Color Colorless to yellow BASF MSDS

Melting Point (°C) -26 BASF MSDS

Boiling Point (°C @ 19 hPa) 306-307 BASF MSDS

Density (g/cm3 @ 20°C) 0.92 BASF MSDS

Flash point (°C) 142 BASF MSDS

Ignition Temperature (°C) 225 BASF MSDS

Vapor Pressure (mbar) 0.0008 (@ 20°C)

0.02 (@ 55°C) BASF MSDS

Partition Coefficient (Log Pow) 4.15 BASF MSDS

Viscosity Dynamic (@ 25°C) 8 mPa.s. BASF MSDS

Water Solubility (g/L @ 20°C) 1g/L BASF MSDS

pH 9.1 BASF MSDS

III. HUMAN HEALTH ASSESSMENT

A. Summary of Toxicity Data 

Acute Oral Toxicity

The acute oral LD50 for N-(n-octyl)-2-pyrrolidone, was found to be 2,050 mg/kg bw. 

Graded dose levels (630-5,000 mg/kg) of N-(n-octyl)-2-pyrrolidone were administered to 

five groups of fasted Wistar-strain albino rats (5 male, 5 female per group). The animals 

were observed for pharmacological effects, external signs of toxicity and mortality over a 

14-day period. At the 630 mg/kg dose level, no gross changes were observed. The gastric 

mucosa was moderately reddened and intestinal mucosa severely reddened in 1 female 
10

which died at 24 hrs. At the 1,000 mg/kg dose level, 5 rats showed no gross changes. The 

other five were determined to have irritation to the intestinal and gastrointestinal mucosa, 

abscess on abdominal cavity and abscess/lesions on lungs. 3 female rats died at 24 hrs. At 

the 1,580 mg/kg dose level, 7 rats showed no gross changes. 1 rat died at 6 hrs with 

intestinal mucosa moderately reddened and two others at 24 hrs with gastrointestinal 

mucosa reddened and multiple lobes of liver blanched. At 2,520 mg/kg dose level, no 

gross changes were observed in any rats and one died at 2 days also with no gross 

changes observed. At the highest dose of 5,000 mg/kg, 1 rat survived with no gross 

changes observed. The other 9 died started at 3 hrs and ranging to 3 days and 

observations included test article in stomach and intestine, lobes of liver 

mottled/blanched and kidneys blanched, loose feces and forestomach reddened. The 

NOAEL was determined to be 2,050 mg/kg. (MRID 45511801)

Dermal Toxicity

The acute dermal LD50 for N-(n-octyl)-2-pyrrolidone when tested undiluted was 

determined to be greater than 2,000 mg/kg bw. Six New Zealand white rabbits each 

received a single dermal application of undiluted N-(n-octyl)-2-pyrrolidone at a dose 

level of 2,000 mg/kg bw. The skins of 3 animals were abraded, while the remaining 

animals’ skin remained intact. Test sites were occluded for 24 hours after treatment and 

daily thereafter for a total of 14 days. A gross necropsy was performed on all animals. 

The skin at the test sites showed crust formation, scaling and scarring. No gross internal 

changes were observed in any of the animals. There was no mortality reported and the 

NOAEL was 2,000 mg/kg bw. (MRID 45511802)

Inhalation Toxicity

No inhalation toxicity studies were available in the database.

Primary Eye Irritation

N-(n-octyl)-2-pyrrolidone was found to be extremely irritating when tested as sold, with 

wash procedures reducing the severity of the irritation observed. The 2% aqueous 

suspension was nonirritating with and without washout procedures. Nine New Zealand 

white rabbits received a single intra-ocular application of 0.1 mL of N-(n-octyl)-2-

pyrrolidone. In both assays the eyes of 6 animals remained unwashed for 24 hours while 

the eyes of the remaining 3 animals were washed 30 seconds after instillation of the test 

materials. Observations of ocular irritation were recorded 24, 48, and 72 hours following 

instillation of test materials. Additional readings were made at 4, 7, 14, and 21 days in the 

assay where N-(n-octyl)-2-pyrrolidone was tested as sold. The eyes were scored for 

corneal opacity, iritis, conjunctivitis and other effects. The unwashed eyes resulted in 

cornea opacity becoming opaque and iris invisible and covering greater than threequarters up to the whole area of eye. Most irises were many folds above normal, 

congested and swollen. However they were still reacting to light but sluggish reaction. 

The conjunctivae were mainly red with individual vessels not easily discernible. The 

conjunctivae were mainly swollen with lids about half-closed. There was slight discharge 

from the conjunctivae with some animals showing signs of moistening of the lids and 

hairs adjacent to lids. N-(n-octyl)-2-pyrrolidone is considered extremely irritating. 

(MRID 45511803)
11

Primary Skin Irritation

N-(n-octyl)-2-pyrrolidone was found to be irritating to rabbit skin when tested as sold, 

and minimally irritating as a 2% suspension. The backs of 6 New Zealand white rabbits 

were closely clipped and the skin on the right side was abraded by making longitudinal 

epidermal incisions. The skin on the left side was left intact. A single application of 0.5 

mL of N-(n-octyl)-2-pyrrolidone, tested as sold, was made to each test site. In a second 

assay, an additional 6 rabbits received single applications of a 2% aqueous suspension of 

n-(n-octyl)-2-pyrrolidone. In both assays, the wrapping and compound were removed at 

24 hours and the sites scored at 24 and 72 hours for erythema and edema using the Draize 

scale. The mean scores at 24 and 72 hours were averaged to yield a primary irritation 

index of 7.45 for N-(n-octyl)-2-pyrrolidone, when tested as sold, and 0.50 when tested as 

a 2% gravimetric aqueous suspension. (MRID 45511803)

Dermal Sensitization

Twenty female albino guinea pigs received intradermal injections of 0.05% v/v N-(noctyl)-2-pyrrolidone in water and in Freund’s complete adjuvant (FCA) as well as FCA 

in water alone. One week after the injections, the same interscapular area was covered for 

48 hours with a patch saturated with N-(n-octyl)-2-pyrrolidone 30% v/v in distilled water. 

During this induction phase, 10 control animals were treated similarly with the exception 

that the test material was omitted from the injections and topical applications. Two weeks 

after induction period, the test and control animals were challenged topically using a 

patch saturated in 0.2 mL N-(n-octyl)-2-pyrrolidone, 10% v/v in distilled water applied to 

an anterior site on the flank and N-(n-octyl)-2-pyrrolidone, 5% v/v in distilled water 

applied in a similar manner to a posterior site. The patches were sealed to the flank 

covered for 24 hours. The challenge sites were evaluated at 24, 48, and 72 hours after 

patch removal. N-(n-octyl)-2-pyrrolidone produced evidence of delayed contact 

hypersensitivity in 2 of the 20 test animals. (MRID 45511806)

The results of the available acute toxicity studies are summarized in Table 2.

Acute Toxicity

Table 2. Acute Toxicity Profile of N-(n-octyl)-2-pyrrolidone

Study Type Results

Toxicity 

Category MRIDs # /Reference

Acute Oral – rat LD50 = 2050 III Nitka & Palanker 1986

MRID 45511801

Acute Dermal - rabbit >2000 mg/kg III Nitka & Palanker 1986

MRID 45511802

Acute Inhalation - N/A N/A N/A N/A

Primary Eye Irritation -

rabbit

Extremely irritating N/A Nitka & Palanker 1986

MRID 45511803

Primary Skin Irritation -

rabbit

Extremely irritating N/A Nitka & Palanker 1986

MRID 45511803

Dermal Sensitization Guinea pig maximization test 

Positive for dermal sensitization 

in 2 of 20 animals tested

N/A Reagan & Laveglia 1988

MRID 45511806
12

Subchronic Toxicity – Rats

In a 28-day oral toxicity study in rats (MRID 45511805), the no-effect level of N-(noctyl)-2-pyrrolidone was determined to be 55 mg/kg/day. At 320 mg/kg/day specific 

changes in general health, body weight gain, hematological and biochemical parameters 

were recorded. N-(n-octyl)-2-pyrrolidone formulated as a solution in corn oil, was 

administered to rats (5 males, 5 females per dosage level) by intragastic intubation at 

dosage levels of 0, 5, 55, or 320 mg/kg/day. Treatment was carried out once daily for 28 

consecutive days. Similarly, control animals received corn oil (5mL/kg/day) included: 

Statistically significant observations noted at the high dose level of 320 mg/kg day 

included: lower body weight gains in females (week 3); lower packed cell volume (PCV) 

and red blood cell counts in males, corpuscular hemoglobin concentration (MCHC) in 

males; and higher glutamic pyruvic transaminase levels in females. In all other respects 

including food consumption, organ weights, macroscopic and microscopic pathology, no 

changes were noted that were considered to be treatment-related.

In a 90-day dietary toxicity study in rats (MRID 42668316), N-(n-octyl)-2-pyrrolidone 

was administered orally via diet to rats at dosage levels of 0, 60, 600, and 6,000 ppm

(equivalent to 0, 6, 60 and 600 mg/kg/day). Due to the lack of toxicity at the high-dose 

level, the concentration of the test diet was increased from 6,000 to 8,000 ppm (~600 to 

800 mg/kg/day) on study day 29 and from 8,000 to 10,000 ppm (~800 to 1,000 

mg/kg/day) on study day 43. Control animals were fed basal diet. All animals were 

observed daily for clinical signs of toxicity. Body weights and food consumption were 

measured and recorded weekly. Clinical pathology and ophthalmology examinations 

were performed at or near the end of the treatment period. Surviving animals were 

sacrificed at the end of the treatment period. All tissues collected from control and highdose animals, all tissues from animals sacrificed during the study and the lungs, liver, 

kidneys and gross lesions from all low- and mid-dose animals were processed for 

histopathological examination. N-(n-octyl)-2-pyrrolidone produced signs of systemic 

toxicity in both males and females at the 10,000 ppm level. Reduced body weight gain 

and/or food consumption, increased absolute and relative liver weights and minimal to 

mild hepatocyte hypertrophy were observed in the 10,000 ppm group. No treatmentrelated mortalities or clinical signs of toxicity were observed during the study and no 

treatment-related differences were noted in the clinical pathology, ophthalmology or 

gross necropsy observations for males or females in any of the study groups. No 

treatment related changes were observed in body weight gain, feed consumption, organ 

weights and histopathology for males or females in the 60 and 600 ppm groups. Based on 

the study, a dose level of 600 ppm (equivalent to 60 mg/kg/day) was considered the 

NOAEL following dietary administration of N-(n-octyl)-2-pyrrolidone for at least 90 

days. 

In a 90-day oral toxicity study in dogs (MRID 42668317), a dose level of 30 mg/kg/day 

was determined to be the NOAEL. N-(n-octyl)-2-pyrrolidone was administered orally via 

capsule at dosage levels of 0, 30, 90, and 240 mg/kg/day. All animals were observed 

daily for clinical signs of toxicity. After treatment, all surviving animals were subjected 

to complete necropsy with histological examination. Dose related neurological signs and 

body weight loss were observed at 90 and 240 mg/kg/day levels. Also at 90 and 240 
13

mg/kg/day, changes in clinical pathological parameters were observed and were doserelated. In addition, dose-related increases in both absolute and relative liver weights 

were observed in all groups but were significant in only the 90 and 240 mg/kg/day 

groups. One female death occurred on day 42 in the 240 mg/kg/day group.

Chronic Oral Toxicity

No chronic studies were available in the database.

Developmental and Reproductive Toxicity

Developmental studies - Rats

In the developmental toxicity study (MRID 42668318), N-(n-octyl)-2-pyrrolidone was 

administered orally by gavage, once daily, to pregnant female Wistar rats from day 6 

through day 15 post coitum, at dosages of 0, 50, 200, or 800 mg/kg bw/day in order to 

assess the effects on embryonic and fetal development. At 800 mg/kg/day, 1 dam died 

after the 7th and 1 after the 10th test article administration. The females of this group had 

marked clinical signs of reaction to treatment, reduced food consumption, slight 

bodyweight loss during the first day of dosing and reduced corrected bodyweight gain. 

The mean fetal body weight was reduced at this dosage, combined with a delay of 

skeletal ossification. At 50 or 200 mg/kg/day, no effects of treatment with the test article 

on maternal or fetal parameters were evident. Based on the results of this study, the no 

observed adverse effect level (NOAEL) for the maternal and fetal parameters was 

considered to be 200 mg/kg bw/day. N-(n-octyl)-2-pyrrolidone did not reveal any 

teratogenic potential up to and including the highest dose tested (HDT) level of 800 

mg/kg bw/day when administered to pregnant Wistar rats under the conditions described 

for this study. 

Reproduction studies - Rats

No reproductive toxicity studies are available for N-(n-octyl)-2-pyrrolidone.

Immunotoxicity

No immunotoxicity studies were available in the database for N-(n-octyl)-2-pyrrolidone, 

however, no triggers for immunotoxicity were observed in the available database.

Neurotoxicity

No neurotoxicity studies were available in the database for N-(n-octyl)-2-pyrrolidone.

Mutagenicity and Genotoxicity

N-(n-octyl)-2-pyrrolidone was tested, as sold, in the Ames assay (MRID 42668319) with 

Salmonella typhimurium strains TA 1535, TA 1537, TA 1538, TA 98, and TA 100. Tests 

were conducted in all 5 strains with and without metabolic activation (induced S-9 rat 

liver preparations). The entire assay was performed twice. No mutagenic activity was 

demonstrated by N-(n-octyl)-2-pyrrolidone when tested as sold in the Ames assay. 
14

In a Mouse Lymphoma Assay (MRID 42668320), N-(n-octyl)-2-pyrrolidone was tested 

for its potential to induce mutations at the thymidine Kinase locus of L5128Y TK+/-

mouse lymphoma cells in the presence and absence of exogenous metabolic activation. 

Based on the results of a range finding test the test article was tested in the assay at doses 

ranging 0.005 to 100 μL/mL which produced varying degrees of reduction in cell growth. 

The results of this assay indicate that N-(n-octyl)-2-pyrrolidone produced a negative 

response in cultures treated in either the absence of exogenous activation or the presence 

of Aroclor-induced rat liver S-9 mix. 

In a Mouse Micronucleus Assay (MRID 42668321), mice were administered N-(n-octyl)-

2-pyrrolidone by intragastric gavage at a dose level of 1,720 mg/kg, based on results of a 

preliminary toxicity test. Bone marrow smears were obtained at 24, 48, and 72 hours 

post-dosing and examined for the presence of micronuclei in polychromatic and 

normochromatic erythrocytes. The ratio of polychromatic to normochromatic 

erythrocytes (P/N ratio) was also assessed. At sampling times mice treated with N-(noctyl)-2-pyrrolidone showed no significant increase in frequency of micronucleated 

polychromatic erythrocytes, nor was there a significant decrease in P/N ratio at any of the 

sampling times. N-(n-octyl)-2-pyrrolidone was found to be non-mutagenic at dose level 

of 1,720 mg/kg in this in vivo cytogenetic test.

Carcinogenicity

No carcinogenicity studies were available in the database for N-(n-octyl)-2-pyrrolidone.

The Agency used a qualitative structure activity relationship (SAR) database, DEREK11, 

to determine if there were structural alerts for potential carcinogenicity of for N-(n-octyl)-

2-pyrrolidone. No structural alerts for carcinogenicity were identified for N-(n-octyl)-2-

pyrrolidone. In the absence of any structural alerts and lack of mutagenicity concerns, N-

(n-octyl)-2-pyrrolidone is not expected to be carcinogenic.

Metabolism and Pharmacokinetics

No metabolism or pharmacokinetics studies were available in the database for N-(noctyl)-2-pyrrolidone.
15

Table 3. Toxicology Profile for N-(n-octyl)-2-pyrrolidone

Guideline No./ 

Study Type

Doses Levels MRID No. 

(year)/References

Results

28 Day oral 

toxicity – rat

5, 55 and 320 

mg/kg/day

Smith et al. 1989

MRID 45511805

NOAEL = 55 mg/kg/day

LOAEL = 320 mg/kg/day based on general health, body 

weight gain, hematological and biochemical parameters. 

90 Day oral 

toxicity – rat

(N-(n-octyl)-2-

pyrrolidone)

60, 600 and 

6,000 ppm in 

diet initially 

and increased 

to 8,000 and 

10,000 near 

conclusion of 

study

Liao 1991

MRID 42668316

NOAEL = 600 ppm (53 mg/kg)

LOAEL = 

Signs of systemic toxicity in both males and females 

were observed at 10000 ppm. Reduced body weight 

gain and/or food consumption, increased absolute and 

relative liver weights and minimal to mild hepatocyte 

hypertrophy were observed in the 10000 ppm group. 

90 day oral 

toxicity – dog

(N-(n-octyl)-2-

pyrrolidone)

30, 90 240 

mg/kg/day

Liao 1991

MRID 42668317

NOAEL = 30 mg/kg/day

LOAEL = 90 mg/kg/day based on changes to clinical 

pathological parameters (decrease in A/G ratio and 

increase in alkaline phosphatase and globulin and 

decrease in RBC, Hgb, Hct, albumin, and GGT) and 

statistically significant dose-related increases in both 

absolute and relative liver weights. Also a dose-related 

minimal or mild hepatocellular hypertrophy was 

observed.

Developmental 

Toxicity - rats

(N-(n-octyl)-2-

pyrrolidone)

0, 50, 200 and 

800 mg/kg 

bw/day

Biedermann 1991

MRID 42668318

Maternal NOAEL = 200 mg/kg bw /day

Maternal LOAEL = 800 mg/kg bw/day based on ruffled 

fur, ventral recumbency, somnolence, apathy, dyspnea 

and comatose state. Also reduction in food consumption 

and slight body weight loss during the first days of 

dosing and reduced corrected body weight gain.

Developmental NOAEL = 200 mg/kg 

Developmental LOAEL = 800 mg/kg based on 

statistically significantly reduced body weight and delay 

in skeletal ossification correlated with the severe 

maternal toxicity observed at this dosage. 

AMES Test

(N-(n-octyl)-2-

pyrrolidone)

Up to 1500 

μg/plate

Jones et al. 1989

MRID 42668319

No evidence of mutagenic potential as obtained in this 

bacterial test system

Mouse 

Lymphoma 

Mutagenesis 

Assay

(N-(n-octyl)-2-

pyrrolidone)

Kirby 1990

MRID 42668320

Test article produced a negative response in cultures 

treated in either the absence of exogenous activation or 

the presence of Aroclor-induced rat liver S-9. 

Mouse 

Micronucleus Test

(N-(n-octyl)-2-

pyrrolidone)

Up to 1720 

mg/kg

Proudlock et al. 

1989

MRID 42668321

At all sampling times mice treated with test substance 

showed no significant increase in the frequency of 

micronucleated polychromatic erythrocytes. No 

significant decrease in the ratio of polychromatic to 

normochromatic erythrocytes. No evidence of 

mutagenic potential or bone marrow cell toxicity when 

administered orally in this in vivo test procedure.
16

B. Toxicity Endpoint Selection

In the toxicity database, the lowest NOAEL was 30 mg/kg/day based on the 90-day 

toxicity study in dogs based on changes in clinical pathological parameters (decrease in 

A/G ratio and increase in alkaline phosphatase and globulin and decrease in RBC, Hgb, 

Hct, albumin, and GGT) and statistically significant dose-related increases in both 

absolute and relative liver weights. Also a dose-related minimal or mild hepatocellular 

hypertrophy was observed. 

Table 4. Summary of Toxicological Doses and Endpoints for N-(n-octyl)-2-pyrrolidone for Use in Human 

Health Risk Assessment

Exposure/Scenario Point of Departure and 

Uncertainty/Safety Factors

RfD, PAD, 

LOC for Risk 

Assessment

Study and Toxicological Effects

Acute dietary 

(General population 

including infants and 

children)

An acute effect was not found in the database therefore an acute dietary assessment is not 

necessary.

Chronic dietary 

(All populations)

NOAEL= 30mg/kg/day 

UFA = 10 x

UFH = 10 x

FQPA SF = 3 x

Chronic RfD = 

30 mg/kg/day

cPAD = 0.1

mg/kg/day

[Chronic Toxicity/

Carcinogenicity-dog] LOAEL = 90

mg/kg/day based on based 

neurological signs, body weight and 

changes in clinical pathological 

parameters

Incidental oral shortterm 

(1 to 30 days)

NOAEL= 30 mg/kg/day 

UFA = 10 x

UFH = 10 x

FQPA SF = 3 x

LOC for MOE 

= 300

[Chronic Toxicity/

Carcinogenicity-dog] LOAEL = 90

mg/kg/day based on based 

neurological signs, body weight and 

changes in clinical pathological 

parameters

Incidental oral 

intermediate-term 

(1 to 6 months)

NOAEL= 30 mg/kg/day

UFA= 10 x

UFH= 10 x

FQPA SF = 3 x

LOC for MOE 

= 300

[Chronic Toxicity/

Carcinogenicity-dog] LOAEL = 90

mg/kg/day based on based 

neurological signs, body weight and 

changes in clinical pathological 

parameters

Dermal short-term 

(1 to 30 days)

Dermal (or oral) study 

NOAEL = 30 mg/kg/day 

(dermal absorption rate = 100 

%

UFA = 10 x

UFH = 10 x

FQPA SF = 3 x

LOC for MOE 

= 300

[Chronic Toxicity/

Carcinogenicity-dog] LOAEL = 90

mg/kg/day based on based 

neurological signs, body weight and 

changes in clinical pathological 

parameters

Dermal intermediateterm

(1 to 6 months)

Dermal (or oral) study 

NOAEL = 30 mg/kg/day 

(dermal absorption rate = 100 

%

UFA = 10 x

UFH = 10 x

FQPA SF = 3 x

LOC for MOE 

= 300

[Chronic Toxicity/

Carcinogenicity-dog] LOAEL = 90

mg/kg/day based on based 

neurological signs, body weight and 

changes in clinical pathological 

parameters

Inhalation short-term 

(1 to 30 days)

Inhalation (or oral) study 

NOAEL= 30 mg/kg/day 

(inhalation absorption rate = 

LOC for MOE 

= 300 

[Chronic Toxicity/

Carcinogenicity-dog] LOAEL = 90

mg/kg/day based on based 
17

100%)

UFA = 10 x

UFH = 10 x

FQPA SF = 3 x

neurological signs, body weight and 

changes in clinical pathological 

parameters

Inhalation 

(1 to 6 months)

Inhalation (or oral) study 

NOAEL = 30 mg/kg/day 

(inhalation absorption rate = 

100%)

UFA = 10 x

UFH = 10 x

FQPA SF = 3 x

LOC for MOE 

= 300 

[Chronic Toxicity/

Carcinogenicity-dog] LOAEL = 90

mg/kg/day based on based 

neurological signs, body weight and 

changes in clinical pathological 

parameters

Cancer (Oral, dermal, 

inhalation)

Based on the lack of mutagenicity in N-(n-octyl)-2-pyrrolidone and the absence of 

structural alerts in the DEREK analysis, N-(n-octyl)-2-pyrrolidone is unlikely to be 

carcinogenic.

UFA = extrapolation from animal to human (interspecies). UFH = potential variation in sensitivity among members 

of the human population (intraspecies). UFL = use of a LOAEL to extrapolate a NOAEL. UFS = use of a short-term 

study for long-term risk assessment. UFDB = to account for the absence of data or other data deficiency. FQPA SF 

= Food Quality Protection Act Safety Factor. PAD = population adjusted dose (a = acute, c = chronic). RfD = 

reference dose. MOE = margin of exposure. LOC = level of concern.

C. Special Considerations for Infants and Children

Section 408 of the FFDCA provides that EPA shall apply an additional margin of safety 

for infants and children in the case of threshold effects to account for prenatal and post 

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

determines that a different margin of safety will be safe for infants and children. EPA 

concludes that the FQPA safety factor could be reduced to 3X for N-(n-octyl)-2-

pyrrolidone for the following reasons:

i. The toxicity database for N-(n-octyl)-2-pyrrolidone consists of 90-day oral 

toxicity studies in rats and dogs, several mutagenicity studies and a developmental 

toxicity study. While there are no reproductive, neurotoxicity and chronic toxicity 

studies for N-(n-octyl)-2-pyrrolidone, there is no evidence of effects on 

reproductive parameters or any effects suggestive of neurotoxicity from the 

available subchronic studies. Additionally, the most sensitive endpoint selected 

seen in the 90-day dog oral toxicity study is based on hemtatological and clinical 

chemistry parameters; increases in both absolute and relative liver weights; and 

reduction in body weight gain/food consumption-effects which are not expected 

to be progressive and for which the resultant exposure assessment is likely to be 

protective of chronic effects and characterize toxicity potential of N-(n-octyl)-2-

pyrrolidone. Although additional data are unlikely to indicate more sensitive 

effects, EPA has retained a FQPA factor of 3X as a database uncertainty factor.

No inhalation toxicity studies were available in the database; however, the only 

potential inhalation exposure to N-(n-octyl)-2-pyrrolidone is to pesticide 

applicators, and, even assuming that such exposure has some relevance to 

decisions on the FQPA safety factor, the inhalation exposure to N-(n-octyl)-2-

pyrrolidone is negligible in comparison to exposure under other pathways. In 
18

these circumstances, neither retention nor removal of the FQPA safety factor 

would have a meaningful impact on assessment of risk from inhalation exposure. 

ii. No evidence of immunotoxicity was observed in the available database. Slight 

changes in the clinical pathological parameters (decreases in albumin/globulin 

ratio and globulin levels) were not considered as an indication of an immunotoxic 

response since no effects on blood lymphocytes and no adverse findings in the 

spleen and thymus. Therefore, an immunotoxicity study is not required. 

iii. There are no residual uncertainties identified in the exposure databases. As 

described earlier, EPA used worst case assumptions for the dietary food exposure 

assessment. EPA made conservative (protective) assumptions in the ground and 

surface water modeling used to assess exposure to N-(n-octyl)-2-pyrrolidone in 

drinking water. EPA used similarly conservative assumptions to assess 

residential post application exposure of children as well as incidental oral 

exposure of children 1-2. These assessments will not underestimate the exposure 

and risks posed by N-(n-octyl)-2-pyrrolidone.

IV. EXPOSURE ASSESSMENT

A. Dietary Exposure:

In evaluating dietary exposure to the N-(n-octyl)-2-pyrrolidone, EPA considered exposure 

under the petitioned for exemptions from the requirement of a tolerance. EPA assessed dietary 

exposures from N-(n-octyl)-2-pyrrolidone in food as follows:

 i. Acute exposure. No adverse effects attributable to a single exposure of N-(n-octyl)-2-

pyrrolidone were seen in the toxicity databases. Therefore, acute dietary risk assessment 

for N-(n-octyl)-2-pyrrolidone is not required.

 ii. Chronic exposure. In conducting the chronic dietary exposure assessment using the 

Dietary Exposure Evaluation Model DEEM-FCIDTM, Version 3.16, EPA used food 

consumption information from the U.S. Department of Agriculture’s National Health and 

Nutrition Examination Survey, What We Eat In America, (NHANES/WWEIA). This 

dietary survey was conducted from 2003 to 2008. As to residue levels in food, no residue 

data were submitted for N-(n-octyl)-2-pyrrolidone. In the absence of specific residue 

data, EPA has developed an approach which uses surrogate information to derive upper 

bound exposure estimates for the subject inert ingredient. Upper bound exposure 

estimates are based on the highest tolerance for a given commodity from a list of highuse insecticides, herbicides, and fungicides. A complete description of the general 

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

in the memorandum entitled “Alkyl Amines Polyalkoxylates (Cluster 4): Acute and 
19

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.

In the dietary exposure assessment, the Agency assumed 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 (if any) between the 

active and inert ingredient 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 Agency believes the assumptions used to estimate dietary exposures lead to an 

extremely conservative assessment of dietary risk due to a series of compounded 

conservatisms. First, assuming that the level of residue for an inert ingredient is equal to 

the level of residue for the active ingredient will overstate exposure. The concentration 

of active ingredients in agricultural products is generally at least 50 percent of the product 

and often can be much higher. Further, pesticide products rarely have a single inert 

ingredient; rather there is generally a combination of different inert ingredients used 

which additionally reduces the concentration of any single inert ingredient in the 

pesticide product in relation to that of the active ingredient.

Second, the conservatism of this methodology is compounded by EPA’s decision to 

assume that, for each commodity, the active ingredient which will serve as a guide to the 

potential level of inert ingredient residues is the active ingredient with the highest 

tolerance level. This assumption overstates residue values because it would be highly 

unlikely, given the high number of inert ingredients, that a single inert ingredient or class 

of ingredients would be present at the level of the active ingredient in the highest 

tolerance for every commodity. Finally, a third compounding conservatism is EPA’s 

assumption that all foods contain the inert ingredient at the highest tolerance level. In 

other words, EPA assumed 100 percent of all foods are treated with the inert ingredient at 

the rate and manner necessary to produce the highest residue legally possible for an 

active ingredient. In summary, EPA chose a very conservative method for estimating 

what level of inert residue could be on food, and then use this methodology to choose the 

highest possible residue that could be found on food and assumed that all food contained 

this residue. No consideration was given to potential degradation between harvest and 

consumption even though monitoring data shows that tolerance level residues are 

typically one to two orders of magnitude higher than actual residues in food when 

distributed in commerce. 

Accordingly, 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. EPA does not believe that this approach 

underestimates exposure in the absence of residue data.

In the case of N-(n-octyl)-2-pyrrolidone, EPA made specific adjustments to the dietary 

exposure assessment to account for the use limitations of N-(n-octyl)-2-pyrrolidone. The 
20

refined herbicide residue profile created by Health Effects Division (HED) for the Inert 

Ingredient Assessment Branch (IIAB) for the dietary estimated exposure model (DEEM) 

was modified to include only commodity residues with active pyraflufen ethyl 

registrations. The residue levels established for the herbicide profile were retained for 

those specific commodities there would be residues for the active ingredient to be used 

with N-(n-octyl)-2-pyrrolidone. In addition, the amount of N-(n-octyl)-2-pyrrolidone that 

may be in formulations is no more than 20% by weight in pesticide formulations. The 

residues and adjustment factor in the original herbicide residue profile were altered so 

that Adjustment Factor 2 in the DEEM input file was set to 1 to reflect a 50% average 

content for inerts. For this analysis, Adjustment Factor 2 was changed to 0.4 to reflect the 

20% inert content, except for cotton commodities which are already exempted from a 

tolerance because of the current 40 CFR 180.1130 exemption for N-(n-octyl)-2-

prryolidone and N-(n-dodecyl)-2-pyrrolidone when used as solvents in cotton defoliant 

formulations containing thidiazuron and diuron as active ingredients.. 

Table 5. Summary of Chronic Dietary Exposure and Risk for N-(n-octyl)-2-pyrrolidone

Population Subgroup cPAD (mg/kg/day) Chronic

Exposure (mg/kg/day) %cPAD

Total U.S. Population

0.1

0.014323 14.3%

All Infants (<1 year old) 0.033758 33.8%

Children 1-2 years old 0.059367 59.4%

Children 3-5 years old 0.041883 41.9%

Children 6-12 years old 0.023487 23.5%

Youth 13-19 years old 0.012444 12.4%

Adults 20-49 years old 0.010126 10.1%

Adults 50+ years old 0.009008 9.0%

Females 13-49 years old 0.010055 10.1%

Based on the analysis of estimated dietary risks for the total U.S. population and various 

population subgroups, the chronic dietary exposure estimates for N-(n-octyl)-2-

pyrrolidone are below the agency’s level of concern for all supported commodities with 

active pyraflufen ethyl registrations. The chronic dietary exposure estimates for the total 

U.S. population is 14.3% and the highest exposed population subgroup, children 1-2 

years old is 59.4% of the chronic population adjusted dose (cPAD).

iii. Cancer exposure. It is concluded that N-(n-octyl)-2-pyrrolidone is unlikely to pose a 

cancer risk in human based on the lack of mutagenicity concerns and the lack of any 

structural alerts for carcinogenicity in Derek analysis. Therefore, a cancer dietary risk 

assessment for N-(n-octyl)-2-pyrrolidone was not conducted. 

B. Residential Exposure

The term “residential exposure” is used in this document to refer to non-occupational, 

non-dietary exposure (e.g., for lawn and garden pest control, indoor pest control, 

termiticides, and flea and tick control on pets). N-(n-octyl)-2-pyrrolidone may be used in 

inert ingredients in pesticide products that are registered for specific uses that may result 
21

in outdoor residential exposures. Based on the use pattern of the active ingredient

pyraflufen ethyl, which includes but is not limited to golf courses, ornamental turf lawns, 

roadsides, parks and sports fields, the major routes of exposure are expected to be 

inhalation and dermal exposure. A screening level residential exposure and risk 

assessment was completed for a sample product containing pyraflufen ethyl. The product 

label includes, among the registered sites of application, “established ornamental turf 

lawns (residential, industrial, and institutional) parks, cemeteries, athletic fields, golf 

courses (fairways, aprons, tees and roughs), sod farms and similar turf areas.” 

The assessment is also based upon information taken from the sample product label and 

from “Standard Operating Procedures for Residential Pesticide Exposure Assessment” 

(January 2013, Health Effects Division, Office of Pesticide Programs, Office of Chemical 

Safety and Pollution Prevention, U.S. Environmental Protection Agency, Washington, 

D.C.). The SOPs may be accessed at http://www.epa.gov/pesticides/science/residential-exposuresop.html. 

The product has a density of 7.66 lb/gallon. The inert comprises 20% of that or, 

1.53 lb inert per gallon of product. 

1.53 lb inert/gal ÷ 128 fl oz/gal = 0.012 lb inert/fl oz product.

The label instructs lawn/turf spray mixtures be made at 8 fl oz product + 120 fl oz 

water. Thus for a gallon of spray mix; 8 fl oz product * 0.012 lb inert/fl oz = 

0.096 lb inert/gal of spray mix.

The label further directs a handler to apply 1.0 fl oz spray mix/1000 ft2. So,

0.096 lb inert/gal spray mix ÷ 128 fl oz/gal = 0.00075 lb inert/fl oz spray mix. 

The Science Advisory Council for Exposure Policy Number 12 (Rev. 22 FEB 

2001) indicates that for residential handlers using a low-pressure hand-wand 

sprayer or a backpack sprayer the handler would apply 5 gallons of spray per day 

or would apply spray to an area of 1000 ft2

/day; further the policy indicates that 

for a residential handler using a hose-end sprayer, 100 gallons of spray would be 

applied per day or 0.5 A/day would be treated. 

Using area treated/day as the basis of comparison, a residential handler using 

either a low-pressure hand-wand or a backpack sprayer would be exposed to 

0.00075 lb inert spray mix/day. (1000 ft2

/day treated at rate of 1.0 fl oz spray 

mix/1000 ft2)

A residential handler using a hose-end sprayer treating 0.5 A/day:

0.5 A = 21,780 ft2. At a rate of 1.0 fl oz inert spray mix/1000 ft2 that equates to 

21.78 fl oz inert spray mix/day. Since there is 0.00075 lb inert/fl oz spray mix:
22

21.78 fl oz inert spray mix/day * 0.00075 lb inert/fl oz spray mix = 0.0163 lb

inert/day (for one half an acre). That further equates to 0.0326 lb inert/A 

application rate.

The Agency notes with interest that in the case of low-pressure hand-wand 

sprayer or backpack sprayer, that typically only a very small amount of a gallon 

of prepared spray mix would typically be used. The same is true for use of a 

hose-end sprayer but to a lesser extent. That leaves nearly a gallon of prepared 

spray mix that is evidently not typically needed for use. The Agency recommends 

that the label be amended to avoid preparation of much more spray mix than 

might typically be needed. The product label appears to be intended primarily for 

commercial use. The application instructions don’t seem suited to typical 

homeowner use. 

As is described in the Standard Operating Procedures, the algorithm used to 

estimate exposure and dose is 

Unit Exposure * amount handled per day ÷ body weight. In this case there is no 

correction for dermal absorption. Lacking data to the contrary, the Agency 

assumes 100 % absorption via the dermal and inhalation routes of exposure. 

Body weight is assumed to be 80 kg.

Table 6. Unit Exposures for Liquid Formulations (mg inert/pound handled)

Route of 

Exposure

Unit 

Exposure

Mg/kg/day Total mg/kg/day Margins of 

Exposure

Manually pressurized 

hand-wand

Dermal 63 0.000591 0.000591 51000

Inhalation 0.018 0.000000169

Backpack sprayer Dermal 130 0.00122 0.00122 25000

Inhalation 0.14 0.00000132

Hose-end sprayer Dermal 13.4 0.00273 0.00273 11000

Inhalation 0.022 0.00000448

Unit Exposure * Amount handled/day ÷ body weight = Average Daily Dose

Manually pressurized hand-wand sprayer

63 mg inert/lb handled * 0.00075 lb inert handled/day ÷ 80 kg bw = 0.000591 mg/kg bw/day (dermal)

0.018 mg inert/lb handled * 0.00075lb inert handled/day ÷ 80 kg bw = 0.000000169 mg/kg bw/day (inhal.)

Total (dermal and inhalation) = 0.000591 mg/kg/day.

The Agency uses the Margin of Exposure (MOE) as an indication of levels of concern. Typically an MOE 

≥ 300 does not exceed the Agency’s level of concern. Since the endpoint of concern for dermal and 

inhalation exposure assessment is based on same effects, the exposure estimates are also combined. 

Margins of Exposure are ratios of the toxicological endpoint of concern (mg/kg bw/day)/average daily 

dose. In this case the endpoint of concern is 30 mg/kg bw/day. Thus

30 mg/kg bw/day/0.000591 mg/kg bw/day = 51000.

Backpack sprayer

130 mg inert/lb handled * 0.00075 lb handled/day ÷ 80 kg bw = 0.00122 mg/kg bw/day (dermal)

0.14 mg inert/lb handled * 0.00075 lb handled/day ÷ 80 kg bw = 0.00000132 mg/kg bw/day (inhal.)

Total (dermal and inhalation) = 0.00122 mg/kg/day.

Thus, 30 mg/kg bw/day/0.00122 mg/kg bw/day = 25000.
23

Hose-end Sprayer

13.4 mg inert/lb handled * 0.0163 lb handled/day ÷ 80 kg bw = 0.00273 mg/kg bw/day (dermal)

0.022 mg inert/lb handled * 0.0163 lb handled/day ÷ 80 kg bw = 0.00000448 mg/kg bw/day (inhal.)

Total (dermal and inhalation) = 0.00273 mg/kg/day.

Thus, 30 mg/kg bw/day/0.00273 mg/kg bw/day = 11000.

Use of a manually pressurized hand-wand sprayer, a backpack sprayer or a hose-end 

sprayer under the conditions described in the product label results in Margins of 

Exposure which > 300 and therefore do not exceed the Agency’s level of concern.

C. Residential Post-Application Exposure

Pesticide products applied to lawns and turf can result in post-application exposures to 

adults and children. Adults typically may experience dermal post-application exposure. 

Children may experience dermal post-application exposure as well as oral exposures that 

result from “hand-to-mouth” activities common to toddlers.

In addition, since the product may be applied to golf courses, post-application exposure 

to golfers (adults and adolescents) is also assessed.

Following the guidance in the Residential SOPs and lacking Turf Transferrable Residue 

data, the Agency assumes 1 % (0.01) of the application rate is biologically available for 

dermal transfer. Earlier the rate of application per acre was calculated to be 0.0326 lb 

inert/A. Therefore, 0.000326 lb inert/A is biologically available for dermal transfer.

In calculations of post-application dermal exposure, the Agency uses Transfer 

Coefficients (cm2

/hr) which are derived from numerous studies of pesticide transfer from 

turfgrass. Lacking compound specific transfer data the default levels for liquid 

formulations are: 180,000 cm2

/hr for adults and for children 1-2 years old 49,000 cm

2

/hr. 

Table 7. Summary Residential Post-Application Exposures and Risks

Activity Exposure (Dose)

mg a.i./kg bw/day

MOE

Toddler short-term oral hand to mouth from contacting treated turf 0.000804 37,300

Toddler incidental oral ingestion of treated soil 0.0193 1554

Toddler oral object to mouth (turfgrass) 0.00000383 7.8M

Adult dermal post applic turf contact 0.0124 2420

Toddler dermal post applic turf contact 0.0236 1270

Total Toddler Combined Exposure1 0.0437 686

Adult golfer post app turf contact 0.0000915 328,000

Child golfer post app turf contact 0.000156 192,000

MOE = Margin of Exposure = No Observable Adverse Effect Level ÷ Average Daily Dose

Dermal, Inhalation and Oral NOAEL = 30 mg a.i./kg bw/day

1 Combined exposure reflects the aggregation of dermal exposure to treated areas and HTM exposure from treated areas (for 

children). *Total Combined Exposures = (NOAEL of 30 mg/kg/day)/ [Daily dose dermal + Daily dose HTM + Daily dose 

incidental oral + Daily dose OTM (mg/kg/day)]

Post-application Dermal Exposure From Contacting Treated Lawn/Turf
24

The algorithm is E = TTR1 * CF1 * TC * ET where

E = Exposure

TTR1 = Turf transferrable residue (μg/cm2

)

CF1 = weight unit conversion factor (0.001 mg/μg)

TC = Transfer coefficient

ET = exposure time (hr/day) (1.5 hr). and where

TTR1 = AR * F * CF2 * CF3

TTR1 = Turf Transferrable Residue on day t (μg/cm2

)

AR = Application Rate

F = Fraction of application rate as transferrable residue (unitless) (1.0%)

CF2 = weight unit conversion factor 4.54 x 108 μg/lb)

CF3 = area unit conversion factor (1.08 x 10-3 ft2

/cm2 or 2.47 x 10-8 acre/cm2)

0.0326 lb inert/A * 0.01 * 4.54 x 108 μg/lb * 2.47 x 10-8 acre/cm2 = 0.00366 μg/cm2

0.00366 μg/cm2 * 0.001 mg/μg * 180,000 cm2

/hr * 1.5 hr/day = 0.99 mg/day ÷ 80 kg bw = 0.0124 mg/kg 

bw/day.

30 mg/kg bw/day/0.0124 mg/kg bw/day = 2420 for an adult

0.00366 μg/cm2 * 0.001 mg/μg * 49,000 cm2

/hr * 1.5 hr/day = 0.269 mg/day ÷ 11.4 kg bw = 0.0236 mg/kg 

bw/day.

30 mg/kg bw/day/0.0236 mg/kg bw/day = 1270 for a toddler

Post-Application Hand-to-Mouth Exposure

E = [HR * (FM * SAH) * ET * N_Replen) * (1-(1-SE)(Freq_HtM/N-Replen))] where:

E = exposure (mg/day)

HR = hand residue loading (mg/cm2

)

FM = fraction hand surface area mouthed/even (fraction/event)

SAH = typical surface area of one hand (cm2

)

ET = exposure time (hr/day)

N_Replen = number of replenishment intervals per hour (intervals/hr)

SE = saliva extraction factor (i.e., mouthing removal efficiency

Freq_HtM = number of hand-to-mouth contacts events per hour (events/hr)

and

HR = Faihands * DE (calculated earlier under dermal post-application exposure)

 SAH * 2

where:

HR = hand residue loading (mg/cm2

)

Faihands = fraction ai (material) on hands compared to total surface residue from dermal 

 transfer coefficient (unitless) 0.06 for liquids

DE = dermal exposure (mg)

SAH = typical surface area of one hand (cm2

).

HR = 0.06 * 0.269 mg = 0.00054 mg/cm2

 150 cm2 * 2
25

E = [0.000054 mg/cm2 * (0.127 * 150 cm2) * 1.5 hr/day * 4 int/hr) * (1-(1-0.48)13.9/4)] = 0.00917 mg/day

Dose mg/kg bw/day = E mg /day = 0.00917 mg/day ÷ 11.4 kg = 0.000804 mg/kg bw/day

 BW kg

MOE = NOAEL = 30 mg/kg bw/day = 37,300

 Dose 0.000804 mg/kg bw/day

Post-application Object-to-Mouth Exposure

E = [OR*CF1*SAMO*(ET* N_Replen) * (1-(1-SEO)

(Freq_OtM/N-Replen))] 

where:

E = exposure (mg/day)

OR = chemical residue loading on the object (turf) on day “t”

CF1 = weight unit conversion factor (0.001 mg/μg)

SAMO = area of the object surface that is mouthed (cm2

/event)

ET = exposure time (hr/day)

N_Replen = number of replenishment intervals per hour (intervals/hr)

SEO = saliva extraction factor (i.e., mouthing removal efficiency)

Freq_OtM = number of object-to-mouth contact events per hour (events/hr)

and where:

OR = AR * FO * CF2 * CF3

OR = chemical residue loading on the object μg/cm2

AR = application rate (lb ai/A) 0.52 lb/A in this case

FO = fraction of residue available on the object (unitless)

CF2 = weight unit conversion factor (4.54 x 108 μg/lb

CF3 = area unit conversion factor (1.08 x 10-3 ft2

/cm2 or 2.47 x 10-8 acre/cm2)

Dose is normalized to body weight as Dose/11.4kg.

OR = 0.0326 lb/A * 0.01 * 4.54 x 108 μg/lb * 2.47 x 10-8 acre/cm2 = 0.00366 μg/cm2 

E = 0.00366 μg/cm2 * 0.001 mg/μg * 10 cm2

/event * (1.5hr/day*4interv/hr) * (1-(1-0.48)(8.8/4) = 0.0000437

mg/day

0.0000437 mg/day ÷ 11.4 kg bw = 0.00000383 mg/kg bw/day and

30 mg/kg bw/day ÷ 0.00000383 mg/kg bw/day = 7.8M

 

Post-application Incidental Soil Ingestion Exposure

Exposure from incidental soil ingestion is calculated as follows:

E = SRt * SIgR * CF1 where

E = exposure/day (mg/day)

SRt = soil residue on day “t” (μg/g)

SIgR = ingestion rate of soil (mg/day) and

CF1 = weight unit conversion factor (1 x 10-6 g/μg) and where

SRt = AR * FS * (1-FD)

t

* CF2 * CF3 * CF4 where
26

SRt = soil residue on day “t” (μg/g)

AR = application rate

FS = fraction of ai (or inert) available in uppermost cm of soil (fraction/cm)

FD = fraction of residue that dissipates daily (unitless)

t = post-application day on which exposure

CF2 = weight unit conversion factor (4.54 x 108 μg/lb)

CF3 = area unit conversion factor (1.08 x 10-3 ft2

/cm2 or 2.47 x 10-8 acre/cm2)

CF4 = soil volume to weight unit conversion factor (0.67 cm3

/g soil).

Dose is normalized to body weight D = E

 BW

D = dose (mg/kg bw/day)

E = exposure (mg/day)

SRt = 0.0326 lb/A * 1 * (1-0.1) * 4.54 x 108 μg/lb * 2.47 x 10-8 acre/cm2 * 0.67 cm3

/g soil = 0.22 mg/day

0.22 mg/day ÷ 11.4 kg bw = 0.0193 mg/kg bw/day

MOE = 30 mg/kg bw/day/0.0193 mg/kg bw/day = 1554

Adult and Adolescent Golfer Post-Application Dermal Exposure may be estimated using the 

convention stated in Science Advisory Council for Exposure draft Policy regarding “Golfer Exposure 

Assessment For Adults and Children” (24 August 2000). The draft policy states that adult and adolescent 

golfer dermal post-application exposure may be calculated as 

DE(t) (mg a.i./kg bw/day) = (TTR(t) (μg/cm2)) * TC (cm2/hr) * hr/day ÷ (CF (1000 μg/mg)) * BW (body 

weight (kg)) Where:

DE(t) = dermal exposure at time (t) attributable to golfing on previously treated turf (mg /kg bw/day).

TTR(t) = turf transferable residue at time t (μg/cm2)

TC = Transfer Coefficient (500 cm2/hr)

hr = exposure period (4 hours)

CF = conversion factor to change μg to mg.

BW = body weight (kg) (80 kg for adult; adjusted (multiplied) by a factor of 1.7 for child golfers)) 

Therefore,

DE = 0.00366 μg/cm2 * 500 cm2/hr * 4 hr/day/1000μg/mg ÷ 80 kg bw = 0.0000915 mg /kg bw/day. 

MOE for adult golfer is 30 mg a.i./kg bw/day ÷ 0.0000915 mg/kg bw/day = 328,000.

The adult dose level is adjusted by a factor of 1.7 to estimate child golfer exposure therefore 0.0000915 mg 

a.i./kg bw/day * 1.7 = 0.000156 mg a.i./kg bw/day. 

MOE for child golfer is 30 mg a.i./kg bw/day ÷ 0.000156 = 192,000.

A MOE of 300 is adequate to protect golfers from dermal post application exposures to treated golf course 

turf. Inhalation exposure is believed to be negligible. 

EPA has calculated the residential post-application exposures. All Margins of Exposures

(MOEs) are > 300 and therefore the use patterns as described do not exceed the 

Agency’s level of concern.
27

V. AGGREGATE RISK AND DETERMINATION OF SAFETY

EPA determines whether acute and chronic pesticide exposures are safe by comparing 

aggregate exposure estimates to the aPAD and cPAD. The aPAD and cPAD represent the 

highest safe exposures, taking into account all appropriate safety factors (SFs). EPA calculates 

the aPAD and cPAD by dividing the PoD by all applicable UFs. For linear cancer risks, EPA 

calculates the probability of additional cancer cases given the estimated aggregate exposure. 

Short-, intermediate-, and chronic-term risks are evaluated by comparing the estimated aggregate 

food, water, and residential exposure to the PoD to ensure that the MOE called for by the product 

of all applicable UFs is not exceeded. 

A. Acute Dietary Risk. An acute aggregate risk assessment takes into account exposure 

estimates from acute dietary consumption of food and drinking water using the exposure 

assumptions discussed in section IV for acute exposure. However there was no hazard 

attributable to a single exposure seen in the toxicity database for N-(n-octyl)-2-pyrrolidone; 

therefore an acute aggregate risk assessment is not required. 

B. Chronic Dietary Risk. A chronic aggregate risk assessment takes into account exposure 

estimates from chronic dietary consumption of food and drinking water using the exposure 

assumptions discussed in section IV for chronic exposure. The chronic analysis was based 

on a 90-day oral toxicity study in dogs with a NOAEL of 30 mg/kg/day and LOAEL of 90

mg/kg/day based on changes clinical pathological parameters (decrease in A/G ratio and 

increase in alkaline phosphatase and globulin and decrease in RBC, Hgb, Hct, albumin, and 

GGT) and statistically significant dose-related increases in both absolute and relative liver 

weights. A 300-fold uncertainty factor (UF) (10x for interspecies extrapolation, 10x for 

intraspecies variation and 3x for FQPA Safety Factor) was incorporated. The chronic dietary 

exposure from food and water to N-(n-octyl)-2-pyrrolidone is 14.3% of the cPAD for the 

U.S. population and 59.4% of the cPAD for children 1-2 yrs old, the most highly exposed 

population subgroup.

C. Aggregate Cancer Risk for U.S. Population. The Agency has not identified any 

concerns for carcinogenicity relating to N-(n-octyl)-2-pyrrolidone; therefore, a cancer dietary 

exposure assessment was not performed and a caner aggregate risk assessment is not a 

concern.

D. Short-Term Aggregate Risk. Short-term aggregate exposure takes into account shortterm residential exposure plus chronic exposure to food and water (considered to be a 

background exposure level). N-(n-octyl)-2-pyrrolidone is used as an inert ingredient in 

pesticide products that are currently registered for uses that could result in short-term 

residential exposure. The Agency has determined that it is appropriate to aggregate chronic 

exposure through food and water with short-term residential exposures. Using the exposure 

assumptions described in Section IV, EPA has calculated the combined short-term 

aggregated food, water, and residential exposures. The adult aggregate MOE was calculated 

to be 1122. Adult aggregate MOE combines average food and water exposure from the 

chronic dietary exposure with high end post application dermal exposure from contact with 
28

treated lawns. As the level of concern is for MOEs that are lower than 300, this MOE is not 

of concern. EPA has concluded the combined short-term aggregated food, water, and 

residential exposures result in an aggregate MOE of 291 for toddlers. Toddler’s residential 

exposure includes total exposures associated with contact with treated lawns (dermal, 

incidental oral ingestion of treated soil and hand-to-mouth exposures). As the level of 

concern is for MOEs that are lower than 300, the estimated aggregate MOEs do not exceed 

the Agency’s level of concern.

Table 8. Short-Term Aggregate Risk Calculations for N-(n-octyl)-2-pyrrolidone

Population

PoD

mg/kg/day LOC1

Max 

Allowable

Exposure2

mg/kg/day

Average

Food & 

Water

Exposure3

mg/kg/day

Residential 

Exposure4

mg/kg/day

Aggregate 

MOE

(food and

residential)5

Adult 30 300 0.1 0.014323 0.0124 1122

Toddler 30 300 0.1 0.059367 0.0437 291

1 The LOC (Level of Concern) is based on the standard inter-, intra-species uncertainty factors and FQPA safety factor totaling 

300.

2 Maximum Allowable Exposure (mg/kg/day) = PoD (Point of Departure)/LOC. 3 Average Food & Water Exposure = Chronic Dietary Exposure Table 5. 4 Residential Exposure = [Oral exposure + Dermal exposure + Inhalation Exposure]. 

5 Aggregate MOE = [PoD/ (Avg Food & Water Exposure + Residential Exposure)].

E. Intermediate-Term Aggregate Risk. Intermediate-term aggregate residential exposure 

takes into account intermediate-term residential exposure plus chronic exposure to food and 

water (considered to be a background exposure level). Pyraflufen ethyl is not currently 

registered for uses that could result in intermediate-term residential exposure so an 

intermediate-term risk assessment for N-(n-octyl)-2-pyrrolidone was not performed. 

F. Determination of Safety. Based on these aggregate risk assessments, EPA concludes that 

there is no concern to adults, infants or children from aggregate exposure to residues of N-(noctyl)-2-pyrrolidone. The short-term aggregate MOE for adults is 1122 and for toddlers are 

291. 

VI. OCCUPATIONAL EXPOSURE/RISK PATHWAY

The representative occupational scenarios selected by the Agency for assessment are

evaluated based on likely maximum application rates for products which may contain the inert 

ingredient, for this assessment the example label previously used for the short-term exposure 

assessment will also be used, and similar application rates for products likely to contain the inert 

ingredient for the intermediate- and long-term exposure durations. Active ingredient application 

rates are corrected for the maximum amount of inert ingredient likely to be in the final 
29

formulations to determine exposure and risk from exposure to the inert ingredient by 

fungicide/insecticide or herbicide. 

RD traditionally considers a level of concern (LOC) for these risk assessments to be an MOE 

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

However based on how the FQPA safety factor was derived, an additional 3X is included in the 

Occupational MOE bringing the total Occupational MOE to 300.

A. Occupational Handler Risk

Exposure Scenarios

Dermal and inhalation exposure are estimated using the Pesticide Handlers Exposure 

Database (PHED) and Outdoor Residential Exposure Task Force (ORETF) data. The 

analytical techniques are those developed by the Science Policy Council on Exposure 

(ExpoSAC), Health Effects Division, Office of Pesticide Programs, U.S. Environmental 

Protection Agency. The quantitative exposure/risk assessment developed for occupational 

handlers to support the requested exemption for the inert ingredient is based on scenarios 

to represent the highest potential exposure. 

The algorithm used to estimate exposure is:

U.E. * AR * Units Treated/day * absorption factor ÷ body weight.

UE Unit Exposure in mg of material per lb of material handled. Unit Exposures are derived 

in the Pesticide Handlers Exposure Database (PHED) and are recently summarized in the 

“Occupation Pesticide Handler Unit Exposure Surrogate Reference Table” US EPA 

Office of Pesticide Programs, March 2012 (unpublished)

AR Application Rate in lbs of material per unit (acres)

Units Treated/day - - In this case acres treated per day taken from the Health Effects Division Standard 

Operating Procedure 9.1 “Standard Values for Daily Acres Treated in Agriculture” Rev.

25 SEPT 2001 (unpublished) For groundboom sprays on sod farm, 80 A/day.

AF Absorption factor - - in this case assumed to be 100 % by the dermal and inhalation 

routes of exposure

BW Body Weight - - 80 kg for combined adults in the U.S. Taken from “Use of New Human 

Body Weight Data as Presented in the EPA’s Exposure Factors Handbook: 2011 Edition” 

HED “HotSheet” No. 31.

In this case occupational exposures are presented for ground applicators and for 

mixer/loaders preparing and applying liquid formulations. These are the occupational 

activities believed to be associated with the highest exposures relative to the proposed 

label use pattern(s). 

Table 9. Summary of Exposure & Risk to Occupational Handlers From N-(n-octyl)-2-pyrrolidone

Unit Exposure1

(mg inert/lb handled)

Application 

Rate2

(lb inert/unit)

Units 

Treated3

Avg. Daily Exposure4

(mg inert/kg bw/day)

MOE5

Applicator, Open Cab Groundboom
30

1. Unit Exposures are taken from “Occupational Pesticide handler Unit Exposure Surrogate Reference Table”, US EPA Office of 

Pesticide Programs, March 2012. 2. Application Rate = Calculated sample product label. 3. Units Treated are taken from the Health Effects Division Standard Operating Procedure 9.1 “Standard Values for Daily Acres 

Treated in Agriculture: Rev. 25 SEPT 2001 (unpublished).

4. Average Daily Exposure = Unit Exposure * Application Rate * Units Treated ÷ 80 kg Body Weight 5. MOE = Margin of Exposure = NOAEL ÷ ADE. Short term NOAEL = 30 mg/kg bw/day

Dermal and inhalation absorption are assumed to be 100%. The inhalation toxicity and 

dermal toxicity is assumed to be equivalent to oral toxicity. Risks were calculated using 

the Margin of Exposure (MOE) approach, which is a ratio of the exposure to the 

toxicological PoD. Occupational handler MOEs ranged from 4,200 to 4,200,000. The 

Agency’s level of concern for occupational inhalation and dermal exposure is for MOEs 

<300. In this case, the estimated MOEs are greater than 300 based on the assumption of 

100% dermal absorption. Therefore, the estimated MOEs are not of concern for 

occupational handler. 

B. Occupational Post-Application Risk

Exposure Scenarios

The Agency uses the term post-application exposure to describe exposures that occur 

when individuals are present in an environment that has been previously treated with a 

pesticide (also referred to as re-entry 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. Inhalation exposures are not typically calculated for occupational postapplication scenarios because post-application inhalation exposures are generally 

believed to be negligible.

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

Dermal:

Single layer, no glove 

0.0786

Inhalation: 

No respirator 

0.00034

0.0326

lb inert/A

80 A/day Dermal:

Single layer, no glove 0.00256

Inhalation: 

No respirator 0.000011

11,700

2,700,000

Mixing / Loading Liquid

Dermal:

Single layer, no gloves 0.22

Single layer, gloves 

0.0376

Inhalation:

No respirator 

0.000219

0.0326

lb inert/A

80 A/day Dermal:

Single layer, no gloves 

0.0072

Single layer, gloves 

0.0012

Inhalation:

No respirator 

0.00000714

4,200

25,000

4,200,000
31

there are minimal potential risks to workers re-entering fields treated with pesticides 

containing N-(n-octyl)-2-pyrrolidone as inert ingredients. 

VII. CUMULATIVE EXPSOURE 

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.”

EPA has not found N-(n-octyl)-2-pyrrolidone to share a common mechanism of toxicity 

with any other substances, and that N-(n-octyl)-2-pyrrolidone does not appear to produce a toxic 

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

EPA has assumed that N-(-n-octyl)-2-pyrrolidone does not have a common mechanism of 

toxicity with other substances. For information regarding EPA's efforts to determine which 

chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such 

chemicals, see EPA's website at http://www.epa.gov/pesticides/cumulative.

VIII. ENVIRONMENTAL JUSTICE STATEMENT 

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.

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

subgroups according to well-established procedures. In line with OPP policy, RD 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 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 toddlers, 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
32

IX. ENVIRONMENTAL FATE CONSIDERATIONS

Environmental fate data for N-(n-octyl)-2-pyrrolidone could not be found in the 

publically available scientific literature. The EPI ( Estimation Programs Interface) 

SuiteTM was used to model possible environmental fate properties of the N-(n-octyl)-2-

pyrrolidone. EPI SuiteTM is a Windows® - based suite of physical/chemical property and 

environmental fate estimation programs developed by the EPA’s Office of Pollution 

Prevention Toxics and Syracuse Research Corportion (SRC). EPI SuiteTM uses a single 

input to run the following estimation programs: BIOWINTM, WSKOWWINTM, and 

BCFBAFTM. The results from these models are presented below. 

The BIOWINTM model estimates aerobic and anaerobic biodegradability of organic 

chemicals using 7 different models. Two of these are the original Biodegradation 

Probability Program (BPPTM). The seventh and newest model estimates anaerobic 

biodegradation potential.

BIOWIN v4.10 Results for N-(n-octyl)-2-pyrrolidone

Biowin1 (Linear Model Prediction): Biodegrades Fast

Biowin2 (non-Linear Model Prediction): Biodegrades Fast

Biowin3 (Ultimate Biodegradation Timeframe): Weeks

Biowin4 (Primary Biodegradtion Timeframe): Days

Biowin5 (MITI Linear Model Prediction): Readily Degradable

Biowin6 (MITI Non-Linear Model Prediction): Readily Degradable

Biowin7 (Anaerobix Model Prediction): Does Not Biodegrade Fast

Ready Biodgradability Prediction: YES

The WSKOWWINTM model estimates an octanol-water partition coefficient using the 

KOWWINTM program, then estimates a chemical’s water solubility from this value and 

applicable correction factors if any.

WSKOW v1.42 Results for N-(n-octyl)-2-pyrrolidone

Log Kow (estimated): 3.33

Log Kow (experimental): not available from database

Log Kow used by Water solubility estimates: 3.33

Equation used to make Water Sol estimate:

Log S (mol/L) = 0.796 – 0.854 log Kow – 0.00728 MW + Correction 

(Used when Melting Point NOT available)

Correction(s): Value

No Applicable Correction Factors

Log Water Solubility (in moles/L): -3.486

Water Solubility at 25 deg C (mg/L): 64.51
33

The BCFBAFTM program, formerly called BCFWINTM, this program estimates fish 

bioconcentration factor and its logarithm using two different methods. The first is the 

traditional regression based on log Kow plus any applicable correction factors, and is 

analogous to the WSKOWWINTM method. The second is the Arnot-Gobas method, 

which calculates BCF from mechanistic first principles. BCFBAF also incorporates 

prediction of apparent metabolism half-life in fish, and estimates BCF and BAF for three 

trophic levels.

BCFBAF v3.01 Results for N-(n-octyl)-2-pyrrolidone

Summary Results:

Log BCF (regression-based estimate): 1.87 (BCF = 73.3 L/kg wet-wt)

Biotransformation Half-Life (days): 0.133 (normalized to 10 g fish)

Log BAF (Arnot-Gobas upper trophic): 1.65 (BAF = 44.7 L/kg wet-wt)

BCF (Bioconcentration Factor):

Log Kow (estimated): 3.33

Log KOW (Experimental): not avialble from database

Log Kow used by BCF estimate:

Log BCF = 0.6598 log Kow – 0.333 + Correction

Correction(s): Value

No Applicable Correction Factors

Estimated Log BCF = 1.865 (BCF = 73.29 L/kg wet-wt)

Based on the estimated modeling programs, N-(n-octyl)-2-pyrrolidone is believed to be 

readily biodegradable. Also based on the modeling, N-(n-octyl)-2-pyrrolidone is 

estimated to have a Log Kow of 3.33 which can be assumed to be only slightly mobile in 

soils when converted to Log Koc. With primary biodegradation estimated to be days and 

ultimate biodegradation to occur in weeks, N-(n-octyl)-2-pyrrolidone is not expected to 

be very persistent in the environment and is therefore is considered not of concern. Also 

the estimated Bioconcentration factor (BCF) is 73.29 L/kg wet-wt which is not expected 

to be of a concern either.

X. ECOTOXICITY

The Ecological Structure Activity Relationships (ECOSAR) Class Program was used to 

estimate the aquatic toxicity of industrial chemicals. The results of the ECOSAR Program 

are presented below.

ECOSAR v1.00 Class Found: Amides

ECOSAR Class/ Organism/ Duration/ End Pt/ Predicted mg/L (ppm)
34

Amides: Fish 96-hr LC50- 2.249

Amides: Daphnid 48-hr LC50 – 2.006

Amides: Green Algae 96-hr EC50 – 0.185

Neutral Organic SAR (Baseline Toxicity):

Fish 96-hr LC50 – 11.357

Daphnid 48-hr LC50 - 7.697

Green Algae 96-hr EC50 – 5.731

The ECOSAR predictions are reasonably close when compared with the experimental 

test results from BASF MSDS and the ISP MSDS.

BASF MSDS:

Acute toxicity to fish: zebra fish/LC50 (96h): >12.3 - < 44.8 mg/l

Acute toxicity to aquatic invertebrates: Daphnia magna /EC50 (48h): 12.2 mg/l

Toxicity to aquatic plants: green algae/EC50 (96 h): 6.2 mg/l;

green algae/EC50 (72 h): 19.0 mg/l

ISP MSDS:

96 hr. Static LC50 (Bluegill sunfish): 22.5 mg/L

48 hr. Static EC50 (Daphnia Magna): 19.1 mg/L

96 hr. Static EC50 (Selenatrum Capricornutum): 6.20 mg/L; 96 hr. NOEC: 3.26 mg/L

96 hr. Flow-through LC50= 17.8 mg/L (Rainbow Trout)

Bobwhite quail LD50: 1,838 mg/kg (acute oral)

Bobwhite quail LC50: >5,620 ppm (dietary)

Based on the studies mentioned in the BASF and ISP MSDS it can be assumed that N-(noctyl)-2-pyrrolidone is slightly toxic to aquatic fish on an acute basis. Also it can be 

assumed that N-(n-octyl)-2-pyrrolidone is slightly toxic to aquatic invertebrates on an 

acute basis. N-(n-octyl)-2-pyrrolidone is also slightly toxic to bobwhite quail on an acute 

basis. It is practically non-toxic to bobwhite quail on a chronic basis based on the dietary 

LC50. Overall N-(n-octyl)-2-pyrrolidone is not expected to be of great concern with 

respect to ecotoxicity. 

XI. RISK CHARACTERIZATION 

Wagner Regulatory Associates (7217 Lancaster Pike, Suite A. Hockessin, DE 19707) on 

behalf of Nichino America, Inc. (4550 New Linden Hill Road, Suite 501, Wilmington, DE 

19808) is requesting that EPA expand the current N-(n-octyl)-2-pyrrolidone (NOP) tolerance 

exemption. N-(n-octyl)-2-pyrrolidone (CAS Reg. No. 2687-94-7) is currently approved for an 

inert ingredient tolerance exemption listed in 40 CFR 180.1130 when used as a solvent in cotton 

defoliant formulations containing thidiazuron and diuron as active ingredients. Wagner 

Regulatory Associates requested that EPA expand it to include use as an inert ingredient 
35

(solvent) in formulations of pyraflufen-ethyl herbicide at a maximum concentration of 20% 

weight/weight.

N-(n-octyl)-2-pyrrolidone has low acute toxicity. The acute oral LD50 = 2,050 mg/kg for 

rats (Toxiccity Category III). The acute dermal LD50 > 2,000 mg/kg in rabbits (Toxicity category 

III). A primary skin irritation study on rabbits showed that N-(n-octyl)-2-pyrrolidone is 

extremely irritating. The dermal sensitization study on guinea pigs was considered positive. No 

acute inhalation study was available in the database.

There were three subchronic oral toxicity studies available in the database. A 28-day oral 

toxicity study in rats showed changes in general health, reduction in body weight gain and 

changes in hematological and biochemical parameters following treatment with 320 mg/kg/day, 

the highest dose tested, of N-(n-octyl)-2-pyrrolidone. The NOAEL = 55 mg/kg/day. In a 90-day 

oral toxicity study in rats signs of systemic toxicicty, reduced body weight gain and/or food 

consumption, increase absolute and relative liver weights and minimal to mild hepatocyte 

hypertrophy were observed at 6000 ppm, the highest dose tested. The NOAEL was 600 ppm (53 

mg/kg/day). In a 90-day oral toxicity study in dogs, a dose-related increase in both absolute and 

relative liver weights, neurological signs and body weight loss were observed at 90 mg/kg/day. 

The NOAEL was 30 mg/kg/day. 

There were three mutagenicity and genotoxicity studies available in the database for N-

(n-octyl)-2-pyrrolidone. An Ames test, a mouse lymphoma mutagenesis assay and a mouse 

micronucleus test were negative for mutagenicity and genotoxicity. 

No carcinogenicity studies were available in the database for N-(n-octyl)-2-pyrrolidone.

The Agency used a qualitative structure activity relationship (SAR) database, DEREK11, to 

determine if there were structural alerts for potential carcinogenicity of for N-(n-octyl)-2-

pyrrolidone. No structural alerts for carcinogenicity were identified for N-(n-octyl)-2-

pyrrolidone. In the absence of any structural alerts and lack of mutagenicity concerns, N-(noctyl)-2-pyrrolidone is not expected to be carcinogenic.

There was one developmental toxicity study for N-(n-octyl)-2-pyrrolidone performed on 

rats, which were dosed at 0, 50, 200 and 800 mg/kg bw/day. The maternal NOAEL was 

determined to be 200 mg/kg bw/day and the maternal LOAEL was 800 mg/kg bw/day based on 

ruffled fur, ventral recumbency, somnolence, apathy, dyspnea and comatose state. Other adverse 

effects observed were a reduction in food consumption and slight body weight loss during the 

first days of dosing and reduced corrected body weight gain. The developmental NOAEL was 

200 mg/kg and the developmental LOAEL was 800 mg/kg based on statistically significantly 

reduced body weight and delay in skeletal ossification correlated with the severe maternal 

toxicity observed at this dosage. 

There were no reproductive toxicity studies for N-(n-octyl)-2-pyrrolidone. While there 

are no reproductive, neurotoxicity and chronic toxicity studies for N-(n-octyl)-2-pyrrolidone, 

there is no evidence of effects on reproductive parameters or of any effects suggestive of 

neurotoxicity from the available subchronic studies. 
36

No immunotoxicity or neurotoxicity studies were available in the database for N-(noctyl)-2-pyrrolidone.

No metabolism or pharmacokinetic studies were available in the database for N-(n-octyl)-

2-pyrrolidone.

Section 408 of the Federal Food, Drug and Cosmetic Act (FFDCA) provides that EPA 

shall apply an additional margin of safety for infants and children in the case of threshold effects 

to account for prenatal and post natal toxicity and the completeness of the database on toxicity 

and exposure unless EPA determines that a different margin of safety will be safe for infants and 

children. EPA concludes that the FQPA safety factor could be reduced from 10X to 3X for N-(noctyl)-2-pyrrolidone based on lack of increased susceptibility of infants and children from 

exposures to N-(n-octly)-2-pyrrolidone, lack of neurotoxicity and immunotoxicity concerns and 

completeness of the database for risk assessment purpose. 

An acute toxicity endpoint was not established because no endpoint of concern following 

a single exposure was identified in the available studies. A toxicity endpoint for chronic dietary 

assessment and inhalation and dermal exposure assessment was selected at 30 mg/kg/day based 

on the 90-day toxicity study in dogs. This was based on changes in clinical pathological 

parameters (decrease in A/G ratio and increase in alkaline phosphatase and globulin and decrease 

in RBC, Hgb, Hct, albumin, and GGT) and statistically significant dose-related increases in both 

absolute and relative liver weights at the LOAEL of 90 mg/kg/day. An uncertainty factor 300 

was for inter-species extrapolation (10X), intra-individual variability (10X) and FQPA safety 

factor (3X). 

An acute dietary risk assessment was not conducted because no endpoint of concern 

following a single exposure was identified in the available studies. 

A chronic dietary risk assessment was conducted using the endpoint from the 90-day dog 

study. Based on the analysis of estimated dietary risks for the total U.S. population and various 

population subgroups, the chronic dietary exposure estimates for N-(n-octyl)-2-pyrrolidone are 

below the Agency’s level of concern for all supported commodities with active pyraflufen ethyl 

registrations. The chronic dietary exposure estimates for the total U.S. population is 14.3% and 

the highest exposed population subgroup, children 1-2 years old, is 59.4% of the chronic 

population adjusted dose (cPAD).

A cancer dietary exposure assessment was not conducted because the Agency has not 

identified a cancer risk for N-(n-octyl)-2-pyrrolidone. 

The term “residential exposure” is used in this document to refer to non-occupational, 

non-dietary exposure (e.g., for lawn and garden pest control, indoor pest control, termiticides, 

and flea and tick control on pets). N-(n-octyl)-2-pyrrolidone may be used in inert ingredients in 

pesticide products that are registered for specific uses that may result in outdoor residential 

exposures. Based on the use pattern of the active ingredient which includes but is not limited to 

golf courses, ornamental turf lawns, roadside, parks and sports fields, the major route of 

exposure is expected to be inhalation and dermal exposure. A screening level residential 
37

exposure and risk assessment was completed for a representative sample product containing 

pyraflufen ethyl. The 20% limit of formulation for N-(n-octyl)-2-pyrrolidone and total 

application rate of 0.0163 lbs of inert ingredient per half acre was used for risk assessment.

For residential applicator exposure, three use scenarios were used based on the sample 

label, manually pressurized hand-wand, backpack sprayer and hose-end sprayer. The Margins of 

Exposures (MOEs) were calculated to be 51000, 25000 and 11000 respectively. The acceptable 

MOE is for N-(n-octyl)-2-pyrrolidone is 300 or above; therefore these scenarios do not exceed 

the Agency’s level of concern.

For residential post-application exposure, adults and toddlers were assessed separately as 

well as a golfer scenario. The adult contact consists of dermal post-application contact with turf 

while the toddler scenarios include oral hand to mouth, incidental oral ingestion, oral object to 

mouth and dermal turf contact. The resulting MOEs were 2420 for adults and 686 for a total 

toddler combined exposure for all the scenarios. The acceptable MOE for N-(n-octyl)-2-

pyrrolidone is 300 or above; therefore residential post-application exposures do not exceed the 

Agency’s level of concern for N-(n-octyl)-2-pyrrolidone. 

Short-term residential aggregate exposure takes into account short-term residential 

exposure plus chronic exposure to food and water (considered to be a background exposure 

level). N-(n-octyl)-2-pyrrolidone is used as an inert ingredient in some pesticide products that are 

currently registered for uses that could result in short-term residential exposure. The adult shortterm aggregate MOE was calculated to be 1122 and the toddler aggregate MOE to be 291. 

Registration Division’s levels of concern are for MOEs that are less than 300, therefore the 

aggregate exposure MOE are not of concern. 

Occupational exposure scenarios selected by the Agency for assessment are evaluated 

based on likely maximum application rates for products which may contain the inert ingredient. 

The example label and the same application rates were used for the intermediate- and long-term 

exposure durations. Active ingredient application rates are corrected for the maximum amount 

of inert ingredient (20% limit) present in the final formulations to determine exposure and risk 

from exposure to the inert ingredient. The acceptable MOE for N-(n-octyl)-2-pyrrolidone is set 

at 300 or above for occupational exposure assessment. Based on the sample label, the 

occupational exposure scenarios for ground applicators and for mixer/loaders preparing and 

applying liquid formulations were used. These are the occupational activities believed to be 

associated with the highest exposures relative to the proposed label use patterns. Due to the lack 

of data to the contrary, dermal absorption is assumed to be 100%. The inhalation toxicity and 

dermal toxicity was also assumed to be equivalent to oral toxicity. Risks were calculated using 

the MOE approach, which is a ratio of the exposure to the toxicological point of departure (PoD). 

Occupational handler risks consisted of MOEs ranging from 4,200 to 4,200,000 and are 

considered not of concern. The Agency’s level of concern for occupational inhalation and dermal 

exposure for N-(n-octyl)-2-pyrrolidone is for MOEs <300.

Occupational post-application exposure is used to describe exposures that occur when 

individuals are present in an environment that has been previously treated with a pesticide (also 

referred to as re-entry exposure). Such exposures may occur when workers enter previously 
38

treated areas to perform job functions, including activities related to crop production, such as 

scouting for pests or harvesting. This assessment is considered to be a screening level 

assessment, demonstrating that there are minimal potential risks to workers re-entering fields 

treated with pesticides containing N-(n-octyl)-2-pyrrolidone as inert ingredients. Therefore an 

occupational post-application risk assessment was not performed. 

EPA has not found N-(n-octyl)-2-pyrrolidone to share a common mechanism of toxicity 

with any other substances, and that N-(n-octyl)-2-pyrrolidone does not appear to produce a toxic 

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

EPA has assumed that N-(-n-octyl)-2-pyrrolidone does not have a common mechanism of 

toxicity with other substances.

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.

Environmental fate data for N-(n-octyl)-2-pyrrolidone could not be found in the 

publically available scientific literature. The EPI (Estimation Programs Interface) SuiteTM

was 

used to model possible environmental fate properties of the N-(n-octyl)-2-pyrrolidone. Based on 

the estimated modeling programs, N-(n-octyl)-2-pyrrolidone is believed to be readily 

biodegradable. Also based on the modeling, N-(n-octyl)-2-pyrrolidone is estimated to have a Log 

Kow of 3.33 which can be assumed to be only slightly mobile in soils when converted to Log 

Koc. With primary biodegradation estimated to be days and ultimate biodegradation to occur in 

weeks, N-(n-octyl)-2-pyrrolidone is not expected to be very persistent in the environment and is 

therefore considered not of concern. The estimated Bioconcentration factor (BCF) is 73.29 which 

is also not expected to be of a concern 

The Ecological Structure Activity Relationships (ECOSAR) Class Program was used to 

estimate the aquatic toxicity of industrial chemicals. However study citations were also provided 

from both BASF and ISP MSDS. The ECOSAR predictions were reasonably close when 

compared with the experimental test results from BASF MSDS and the ISP MSDS. Based on the 

studies mentioned in the BASF and ISP MSDS it can be assumed that N-(n-octyl)-2-pyrrolidone 

is slightly toxic to aquatic fish on an acute basis. Also it can be assumed that N-(n-octyl)-2-

pyrrolidone is slightly toxic to aquatic invertebrates on an acute basis. N-(n-octyl)-2-pyrrolidone 

is also slightly toxic to bobwhite quail on an acute basis. It is practically non-toxic to bobwhite 

quail on a chronic basis based on the dietary LC50. Overall N-(n-octyl)-2-pyrrolidone is not 

expected to be of great concern with respect to ecotoxicity. 

Taking into consideration all available information on N-(n-octyl)-2-pyrrolidone, EPA 

concludes that there is a reasonable certainty that no harm to any population subgroup will result

from aggregate exposure to N-(n-octyl)-2-pyrrolidone when considering occupational, dietary 

exposure and all other nonoccupational sources of pesticide exposure for which there is reliable 

information. Therefore, the amendment of an exemption from tolerance under 40 CFR 180.1130 

for N-(n-octyl)-2-pyrrolidone (CAS Reg. No. 2687-94-7) when used as a pesticide inert 
39

ingredient solvent in formulations of pyraflufen ethyl herbicide at a maximum concentration of 

20% weight/weight can be considered safe under section 408(q) of the FFDCA.
40

REFERENCES

MRID 45511801. Nitka S., Palanker A.L. Acute Oral LD50 in Rats of N-(n-octyl)-2-pyrrolidone. 

Testing Facility: Consumer Product Testing Bldg. No. 2-15B. 1275 Bloomfield Avenue 

Fairfield, NJ 07006. Sponsor: International Specialty Products 1361 Alps Road. Wayne, NJ 

07470. Study Completion Date: July 30, 1986.

MRID 45511802. Nitka S., Palanker A.L. Acute Dermal Toxicity in Rabbits of N-(n-octyl)-2-

pyrrolidone. Testing Facility: Consumer Product Testing Bldg. No. 2-15B. 1275 Bloomfield 

Avenue Fairfield, NJ 07006. Sponsor: International Specialty Products 1361 Alps Road. Wayne, 

NJ 07470. Study Completion Date: April 23, 1987.

MRID 45511803. Nitka S., Palanker A.L. Primary Ocular Irritation in Rabbits Primary Dermal 

Irritation in Rabbits of N-(n-octyl)-2-pyrrolidone. Testing Facility: Consumer Product Testing 

Bldg. No. 2-15B. 1275 Bloomfield Avenue Fairfield, NJ 07006. Sponsor: International Specialty

Products 1361 Alps Road. Wayne, NJ 07470. Study Completion Date: June 23, 1986.

MRID 45511804. Nitka S., Palanker A.L. D.O.T. Skin Corrosion in Rabbits of N-(n-octyl)-2-

pyrrolidone. Testing Facility: Consumer Product Testing Bldg. No. 2-15B. 1275 Bloomfield 

Avenue Fairfield, NJ 07006. Sponsor: International Specialty Products 1361 Alps Road. Wayne, 

NJ 07470. Study Completion Date: September 24, 1986.

MRID 45511805. Smith C. et al. Twenty-Eight Day oral Toxicity in Rat with Surfadone LP-100 

( N-(n-octyl)-2-pyrrolidone). Testing Facility: Huntingdon Research Centre Ltd. P.O. Box 2. 

Huntingdon, Cambridgeshire PE18 6ES England. Sponsor: International Specialty Products 1361 

Alps Road. Wayne, NJ 07470. Study Completion Date: June 30, 1989.

MRID 45511806. Reagan E.L., Laveglia J. Comedogenic Assay of Surfadone LP-100 (N-(noctyl)-2-pyrrolidone) in New Zealand White Rabbits. Testing Facility: Food and Drug Research 

Laboratories. Division of Enviro/Analysis Corporation. P.O. Box 107 Route 17C. Waverly, NY 

14892-0107. Sponsor: International Specialty Products 1361 Alps Road. Wayne, NJ 07470. 

Study Completion Date: February 29, 1988.

MRID 42668316. Liao J.T.F. Surfadone LP-100 90-Day Dietary Toxicicty Study in Rats Final 

Report. Performing Laboratory: Springborn Laboratories, Inc. (SLS) Life Science Division 553 

North Broadway Spencerville, OH 45887. Sponsor: GAF Chemicals Corporation (International 

Specialty products, Inc.) 1361 Alps Road Wayne, NJ 07470. Study Completion Date: July 2, 

1991.

MRID 42668317. Liao J.T.F. Surfadone LP-100 90-Day Oral (Capsule) Toxicity Study in Dogs 

Final Report. Performing Laboratory: Springborn Laboratories, Inc. (SLS) Life Science Division 

553 North Broadway Spencerville, OH 45887. Sponsor: GAF Chemicals Corporation 

(International Specialty products, Inc.) 1361 Alps Road Wayne, NJ 07470. Study Completion 

Date: July 2, 1991.
41

MRID 42668318. Becker H. Biedermann K. Embryotoxicity Study (Including Teratogenicity) 

with Surfadone LP 100 in the Rat. Performing Laboratory: RCC Research and Consulting 

Company AG P.O. Box, CH 4452 Itingen/Switzerland. Study Completion Date: June 25, 1991.

MRID 42668319. Jones E., Wilson L.A. Ames Metabolic Activation Test to Asses the Potential 

mutagenic Effect of Surfadone LP-100 Surfactant. Performing Laboratory: Huntingdon Research 

Centre Ltd. Huntindon, Cambridgeshire. PE18 6ES, England. Sponsor: GAF Chemicals 

Corporation (International Specialty products, Inc.) 1361 Alps Road Wayne, NJ 07470. Study 

Completion Date: February 3, 1989.

MRID 42668320. Kirby P.E. Evaluation of a Test Article in the L5178Y TK+/- Mouse 

Lymphoma Mutagenesis Assay with Colony Size Evaluation in the Presence and absence of 

Aroclor-induced Rat Liver S-9. Performing Laboratory: SITEK Research Laboratories. 12111 

Parklawn Drive. Rockville. Maryland 20852. Sponsor: International Specialty products, Inc.

1361 Alps Road Wayne, NJ 07470. Study Completion Date: December 3, 1990.

MRID 42668321. Proudlock R.J., Haynes P., Meaking K. Mouse Micronucleus Test on 

Surfadone LP-100 Surfactant. Performing Laboratory: Huntingdon Research Centre Ltd. 

Huntindon, Cambridgeshire. PE18 6ES, England Sponsor: GAF Chemicals Corporation 

(International Specialty products, Inc.) 1361 Alps Road Wayne, NJ 07470. Study Completion 

Date: April 27, 1989.

US EPA (1994) N-(n-Octyl)-2-Pyrrolidone and N-(n-Dodecyl)-2-Pyrrolidone; Tolerance 

Exemptions. US Environmental Protection Agency. Published Date June 22, 1994)

US EPA. (2000) Notice of Filing to establish an exemption from the requirement of a tolerance 

for N (n-octyl)-2-pyrrolidone (Agolex 8®) and N(n-dodecyl)-2-pyrrolidone (Agolex 12®) when 

used as an inert ingredient in or on growing crops, when used as an inert ingredient in or on 

growing crops, when applied to an raw agricultural commodities, or to animals (40 CFR 

180.1001(c) and (e)) US Environmental Protection Agency. Published Date: August 30, 2000.

US EPA. (2006) Inert Reassessments: Two Exemptions from the Requirement of a Tolerance for 

N-(n-dodecyl)-2-pyrrolidone (CAS Reg. No. 2687-96-9) and N-(n-octyl)-2-pyrrolidone (CAS 

Reg. No. 2687-94-7). US Environmental Protection Agency Office of Pollution Prevention and 

Toxic Substances. June 20, 2006.
42

APPENDIX

Derek Nexus Report

Derek Nexus Report

Author

HED

Report date

08 August 2013 10:03:24

Prediction date

08 August 2013 10:02:28

Program version

Derek Nexus: 3.0.1, Nexus: 1.5.0

Compound name

Structure-2

Species

bacterium, mammal

Endpoints

alpha-2-mu-Globulin nephropathy, Anaphylaxis, Bladder urothelial hyperplasia, Carcinogenicity, 

Cardiotoxicity, Cerebral oedema, Chloracne, Cholinesterase inhibition, Chromosome damage in vitro, 

Chromosome damage in vivo, Cumulative effect on white cell count and immunology, Cyanide-type 

effects, Developmental toxicity, Genotoxicity in vitro, Genotoxicity in vivo, Hepatotoxicity, HERG 

channel inhibition in vitro, High acute toxicity, Irritation (of the eye), Irritation (of the gastrointestinal 

tract), Irritation (of the respiratory tract), Irritation (of the skin), Lachrymation, Methaemoglobinaemia, 

Mutagenicity in vitro, Mutagenicity in vivo, Nephrotoxicity, Neurotoxicity, Occupational asthma, Ocular 

toxicity, Oestrogenicity, Peroxisome proliferation, Phospholipidosis, Photo-induced chromosome damage 

in vitro, Photoallergenicity, Photocarcinogenicity, Photogenotoxicity in vitro, Photogenotoxicity in vivo, 

Photomutagenicity in vitro, Phototoxicity, Pulmonary toxicity, Rapid prototypes: adrenal gland toxicity, 

Rapid prototypes: bladder disorders, Rapid prototypes: blood in urine, Rapid prototypes: bone marrow 

toxicity, Rapid prototypes: bradycardia, Rapid prototypes: cardiotoxicity, Rapid prototypes: chromosome 

damage in vitro, Rapid prototypes: hepatotoxicity, Rapid prototypes: kidney disorders, Rapid prototypes: 

mitochondrial dysfunction, Rapid prototypes: nephrotoxicity, Rapid prototypes: splenotoxicity, Rapid 

prototypes: testicular toxicity, Rapid prototypes: thyroid toxicity, Respiratory sensitisation, Skin 

sensitisation, Teratogenicity, Testicular toxicity, Thyroid toxicity, Uncoupler of oxidative phosphorylation

Superendpoints

Carcinogenicity (SUPER), Chromosome damage (SUPER), Genotoxicity (SUPER), Hepatotoxicity 

(SUPER), HERG channel inhibition (SUPER), Irritation (SUPER), Miscellaneous endpoints (SUPER), 

Mutagenicity (SUPER), Ocular toxicity (SUPER), Rapid prototypes: adrenal gland toxicity (SUPER), 

Rapid prototypes: bladder disorders (SUPER), Rapid prototypes: blood in urine (SUPER), Rapid 

prototypes: bone marrow toxicity (SUPER), Rapid prototypes: bradycardia (SUPER), Rapid prototypes: 

cardiotoxicity (SUPER), Rapid prototypes: chromosome damage in vitro (SUPER), Rapid prototypes: 

hepatotoxicity (SUPER), Rapid prototypes: kidney disorders (SUPER), Rapid prototypes: mitochondrial 

dysfunction (SUPER), Rapid prototypes: nephrotoxicity (SUPER), Rapid prototypes: splenotoxicity 
43

(SUPER), Rapid prototypes: testicular toxicity (SUPER), Rapid prototypes: thyroid toxicity (SUPER), 

Reproductive toxicity (SUPER), Respiratory sensitisation (SUPER), Skin sensitisation (SUPER), Thyroid 

toxicity (SUPER)

Constraints

Perceive tautomers true

Perceive mixtures true

Perceive alerts without rules false

Average molecular mass

197.32 (Lhasa Limited, version 1.0)

Exact molecular mass

197.178 (Lhasa Limited, version 1.0)

Log Kp

-1.57 (Potts & Guy, version 1.0 (LogP: BioByte Corp., version 5.3; Average Molecular Mass: Lhasa 

Limited, version 1.0))

Log P

3.31 (BioByte Corp., version 5.3)

Submitted compound

Predictions

Derek KB 2012 1.0

KnowledgeBase name

Derek KB 2012 1.0

KnowledgeBase version

1.0

KnowledgeBase last modified

29 November 2012 11:56:30

KnowledgeBase location

C:/Program Files/Lhasa Limited/Lhasa Knowledge Suite - Nexus 

1.5/KnowledgeBases/org.lhasalimited.pluto.knowledge.derek_1.0.7
44

KnowledgeBase certified by

Lhasa Limited, Leeds, Yorkshire, UK

Nothing to report

Reasoning glossary:

Certain

There is proof that the proposition is true.

Probable

There is at least one strong argument that the proposition is true and there are no arguments against it.

Plausible

The weight of evidence supports the proposition.

Equivocal

There is an equal weight of evidence for and against the proposition.

Doubted

The weight of evidence opposes the proposition.

Improbable

There is at least one strong argument that the proposition is false and there are no arguments that it is true

Impossible

There is proof that the proposition is false.

Open

There is no evidence that supports or opposes the proposition.

Contradicted

There is proof that the proposition is both true and false.
45

Chronic DEEM Output File

US EPA Ver. 3.16, 03-08-d

DEEM-FCID Chronic analysis for HERBICIDE TOLERANCES NHANES 2003-2008 2-day

Residue file name: E:\DEEM\N-(n-octyl)-2-pyrrolidone\N-(n-octyl)-2-pyrrolidone - 300UF -

Pyraflufen-ethyl only - Limit Test 20% - cotton fixed.R08

 Adjustment factor #2 used.

Analysis Date 02-04-2014/09:39:33 Residue file dated: 02-04-2014/08:43:47

Reference dose (RfD, Chronic) = .1 mg/kg bw/day

COMMENT 1: Inert Herbicides Only + 100ppb H2O (Pyraflufen Ethyl Only Limit 20% +cotton)

===============================================================================

 Total exposure by population subgroup

-------------------------------------------------------------------------------

 Total Exposure

 -----------------------------------

 Population mg/kg Percent of 

 Subgroup body wt/day Rfd 

-------------------------------------- ------------- ----------------

Total US Population 0.014323 14.3%

Hispanic 0.016276 16.3%

Non-Hisp-White 0.013779 13.8%

Non-Hisp-Black 0.014223 14.2%

Non-Hisp-Other 0.016768 16.8%

Nursing Infants 0.016287 16.3%

Non-Nursing Infants 0.041560 41.6%

Female 13+ PREG 0.012300 12.3%

Children 1-6 0.047178 47.2%

Children 7-12 0.021230 21.2%

Male 13-19 0.013005 13.0%

Female 13-19/NP 0.011886 11.9%

Male 20+ 0.009928 9.9%

Female 20+/NP 0.009323 9.3%

Seniors 55+ 0.008876 8.9%

All Infants 0.033758 33.8%

Female 13-50 0.010013 10.0%

Children 1-2 0.059367 59.4%

Children 3-5 0.041883 41.9%

Children 6-12 0.023487 23.5%

Youth 13-19 0.012444 12.4%

Adults 20-49 0.010126 10.1%

Adults 50-99 0.009008 9.0%

Female 13-49 0.010055 10.1%

-------------------------------------------------------------------------------
46

Chronic DEEM Input File

Filename: E:\DEEM\N-(n-octyl)-2-pyrrolidone\N-(n-octyl)-2-pyrrolidone - 300UF - Pyraflufen-ethyl 

only - Limit Test 20% cotton fixed.TXT

Chemical: Herbicide Tolerances

RfD(Chronic): .1 mg/kg bw/day NOEL(Chronic): .1 mg/kg bw/day

RfD(Acute): 0 mg/kg bw/day NOEL(Acute): 0 mg/kg bw/day

Date created/last modified: 11-20-2013/12:08:41 Program ver. 3.16, 03-08-d

Comment: Inert Herbicides Only + 100ppb H2O (Pyraflufen Ethyl Only Limit 20% +cotton)

-----------------------------------------------------------------------------------

 EPA Crop Def Res Adj.Factors Comment

 Code Grp Commodity Name (ppm) #1 #2 

---------- ---- ------------------------------- ---------- ------ ------ -------

0103296000 1C Potato, chips 1.000000 1.000 0.400 diuron

0103297000 1C Potato, dry (granules/ flakes) 1.000000 6.500 0.400 diuron

0103297001 1C Potato, dry (granules/ flakes)-b 1.000000 6.500 0.400 diuron

0103298000 1C Potato, flour 1.000000 1.000 0.400 diuron

0103298001 1C Potato, flour-babyfood 1.000000 1.000 0.400 diuron

0103299000 1C Potato, tuber, w/peel 1.000000 1.000 0.400 diuron

0103299001 1C Potato, tuber, w/peel-babyfood 1.000000 1.000 0.400 diuron

0103300000 1C Potato, tuber, w/o peel 1.000000 1.000 0.400 diuron

0103300001 1C Potato, tuber, w/o peel-babyfood 1.000000 1.000 0.400 diuron

0600347000 6 Soybean, seed 20.000000 1.000 0.400 glypho

 Full comment: glyphosate

0600349000 6 Soybean, soy milk 20.000000 1.000 0.400 glypho

 Full comment: glyphosate

0600349001 6 Soybean, soy milk-babyfood or in 20.000000 1.000 0.400 glypho

 Full comment: glyphosate

0600350000 6 Soybean, oil 20.000000 1.000 0.400 glypho

 Full comment: glyphosate

0600350001 6 Soybean, oil-babyfood 20.000000 1.000 0.400 glypho

 Full comment: glyphosate

0603348000 6C Soybean, flour 20.000000 1.000 0.400 glypho

 Full comment: glyphosate

0603348001 6C Soybean, flour-babyfood 20.000000 1.000 0.400 glypho

 Full comment: glyphosate

1100007000 11 Apple, fruit with peel 5.000000 1.000 0.400 2,4-D

1100008000 11 Apple, peeled fruit 5.000000 1.000 0.400 2,4-D

1100008001 11 Apple, peeled fruit-babyfood 5.000000 1.000 0.400 2,4-D

1100009000 11 Apple, dried 5.000000 8.000 0.400 2,4-D

1100009001 11 Apple, dried-babyfood 5.000000 8.000 0.400 2,4-D

1100010000 11 Apple, juice 5.000000 1.300 0.400 2,4-D

1100010001 11 Apple, juice-babyfood 5.000000 1.300 0.400 2,4-D

1100011000 11 Apple, sauce 5.000000 1.000 0.400 2,4-D

1100011001 11 Apple, sauce-babyfood 5.000000 1.000 0.400 2,4-D

1100129000 11 Crabapple 5.000000 1.000 0.400 2,4-D

1100210000 11 Loquat 5.000000 1.000 0.400 2,4-D

1100266000 11 Pear 5.000000 1.000 0.400 2,4-D

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1100310000 11 Quince 5.000000 1.000 0.400 2,4-D

1201090000 12A Cherry 0.250000 1.000 0.400 simazi

 Full comment: simazine

1201090001 12A Cherry-babyfood 0.250000 1.000 0.400 simazi

 Full comment: simazine

1201091000 12A Cherry, juice 0.250000 1.500 0.400 simazi

 Full comment: simazine

1201091001 12A Cherry, juice-babyfood 0.250000 1.500 0.400 simazi

 Full comment: simazine

1202012000 12B Apricot 5.000000 1.000 0.400 2,4-D

1202012001 12B Apricot-babyfood 5.000000 1.000 0.400 2,4-D

1202013000 12B Apricot, dried 5.000000 6.000 0.400 2,4-D

1202014000 12B Apricot, juice 5.000000 1.000 0.400 2,4-D

1202014001 12B Apricot, juice-babyfood 5.000000 1.000 0.400 2,4-D

1202230000 12B Nectarine 0.250000 1.000 0.400 simazi

 Full comment: simazine [peach transl]

1202260000 12B Peach 0.250000 1.000 0.400 simazi

 Full comment: simazine
47

1202260001 12B Peach-babyfood 0.250000 1.000 0.400 simazi

 Full comment: simazine

1202261000 12B Peach, dried 0.250000 7.000 0.400 simazi

 Full comment: simazine

1202261001 12B Peach, dried-babyfood 0.250000 7.000 0.400 simazi

 Full comment: simazine

1202262000 12B Peach, juice 0.250000 1.000 0.400 simazi

 Full comment: simazine

1202262001 12B Peach, juice-babyfood 0.250000 1.000 0.400 simazi

 Full comment: simazine

1203285000 12C Plum 0.250000 1.000 0.400 simazi

 Full comment: simazine

1203285001 12C Plum-babyfood 0.250000 1.000 0.400 simazi

 Full comment: simazine

1203286000 12C Plum, prune, fresh 0.250000 1.000 0.400 simazi

 Full comment: simazine

1203286001 12C Plum, prune, fresh-babyfood 0.250000 1.000 0.400 simazi

 Full comment: simazine

1203287000 12C Plum, prune, dried 0.250000 5.000 0.400 simazi

 Full comment: simazine

1203287001 12C Plum, prune, dried-babyfood 0.250000 5.000 0.400 simazi

 Full comment: simazine

1203288000 12C Plum, prune, juice 0.250000 1.400 0.400 simazi

 Full comment: simazine

1203288001 12C Plum, prune, juice-babyfood 0.250000 1.400 0.400 simazi

 Full comment: simazine

1304175000 13D Grape 1.000000 1.000 0.400 diuron

1304176000 13D Grape, juice 1.000000 1.200 0.400 diuron

1304176001 13D Grape, juice-babyfood 1.000000 1.200 0.400 diuron

1304179000 13D Grape, wine and sherry 1.000000 1.000 0.400 diuron

1400003000 14 Almond 1.000000 1.000 0.400 glypho

 Full comment: glyphosate

1400003001 14 Almond-babyfood 1.000000 1.000 0.400 glypho

 Full comment: glyphosate

1400004000 14 Almond, oil 1.000000 1.000 0.400 glypho

 Full comment: glyphosate

1400004001 14 Almond, oil-babyfood 1.000000 1.000 0.400 glypho

 Full comment: glyphosate

1400059000 14 Brazil nut 1.000000 1.000 0.400 glypho

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1400068000 14 Butternut 1.000000 1.000 0.400 glypho

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1400081000 14 Cashew 1.000000 1.000 0.400 glypho

 Full comment: glyphosate

1400092000 14 Chestnut 1.000000 1.000 0.400 glypho

 Full comment: glyphosate

1400155000 14 Hazelnut 1.000000 1.000 0.400 glypho

 Full comment: glyphosate

1400156000 14 Hazelnut, oil 1.000000 1.000 0.400 glypho

 Full comment: glyphosate

1400185000 14 Hickory nut 1.000000 1.000 0.400 glypho

 Full comment: glyphosate

1400213000 14 Macadamia nut 1.000000 1.000 0.400 glypho

 Full comment: glyphosate

1400269000 14 Pecan 1.000000 1.000 0.400 glypho

 Full comment: glyphosate

1400282000 14 Pistachio 1.000000 1.000 0.400 glypho

 Full comment: glyphosate

1400391000 14 Walnut 1.000000 1.000 0.400 glypho

 Full comment: glyphosate

1500120000 15 Corn, field, flour 1.000000 1.000 0.400 glypho

 Full comment: glyphosate

1500120001 15 Corn, field, flour-babyfood 1.000000 1.000 0.400 glypho

 Full comment: glyphosate

1500121000 15 Corn, field, meal 1.000000 1.000 0.400 glypho

 Full comment: glyphosate

1500121001 15 Corn, field, meal-babyfood 1.000000 1.000 0.400 glypho

 Full comment: glyphosate

1500122000 15 Corn, field, bran 1.000000 1.000 0.400 glypho

 Full comment: glyphosate

1500123000 15 Corn, field, starch 1.000000 1.000 0.400 glypho
48

 Full comment: glyphosate

1500123001 15 Corn, field, starch-babyfood 1.000000 1.000 0.400 glypho

 Full comment: glyphosate

1500124000 15 Corn, field, syrup 1.000000 1.500 0.400 glypho

 Full comment: glyphosate

1500124001 15 Corn, field, syrup-babyfood 1.000000 1.500 0.400 glypho

 Full comment: glyphosate

1500125000 15 Corn, field, oil 1.000000 1.000 0.400 glypho

 Full comment: glyphosate

1500125001 15 Corn, field, oil-babyfood 1.000000 1.000 0.400 glypho

 Full comment: glyphosate

1500401000 15 Wheat, grain 5.000000 1.000 0.400 glypho

 Full comment: glyphosate

1500401001 15 Wheat, grain-babyfood 5.000000 1.000 0.400 glypho

 Full comment: glyphosate

1500402000 15 Wheat, flour 5.000000 1.000 0.400 glypho

 Full comment: glyphosate

1500402001 15 Wheat, flour-babyfood 5.000000 1.000 0.400 glypho

 Full comment: glyphosate

1500403000 15 Wheat, germ 5.000000 1.000 0.400 glypho

 Full comment: glyphosate

1500404000 15 Wheat, bran 5.000000 1.000 0.400 glypho

 Full comment: glyphosate

2003128000 20C Cottonseed, oil 15.000000 1.000 1.000 glypho

 Full comment: glyphosate

2003128001 20C Cottonseed, oil-babyfood 15.000000 1.000 1.000 glypho

 Full comment: glyphosate

3100044000 31 Beef, meat 1.000000 1.000 0.400 diuron

3100044001 31 Beef, meat-babyfood 1.000000 1.000 0.400 diuron

3100045000 31 Beef, meat, dried 1.000000 1.920 0.400 diuron

3100046000 31 Beef, meat byproducts 1.000000 1.000 0.400 diuron

3100046001 31 Beef, meat byproducts-babyfood 1.000000 1.000 0.400 diuron

3100047000 31 Beef, fat 1.000000 1.000 0.400 diuron

3100047001 31 Beef, fat-babyfood 1.000000 1.000 0.400 diuron

3200169000 32 Goat, meat 1.000000 1.000 0.400 diuron

3200170000 32 Goat, meat byproducts 1.000000 1.000 0.400 diuron

3200171000 32 Goat, fat 1.000000 1.000 0.400 diuron

3300189000 33 Horse, meat 1.000000 1.000 0.400 diuron

3500339000 35 Sheep, meat 1.000000 1.000 0.400 diuron

3500339001 35 Sheep, meat-babyfood 1.000000 1.000 0.400 diuron

3500340000 35 Sheep, meat byproducts 1.000000 1.000 0.400 diuron

3500341000 35 Sheep, fat 1.000000 1.000 0.400 diuron

3500341001 35 Sheep, fat-babyfood 1.000000 1.000 0.400 diuron

3600222000 36 Milk, fat 0.300000 1.000 0.400 dicamb

 Full comment: dicamba

3600222001 36 Milk, fat-baby food/infant formu 0.300000 1.000 0.400 dicamb

 Full comment: dicamba

3600223000 36 Milk, nonfat solids 0.300000 1.000 0.400 dicamb

 Full comment: dicamba

3600223001 36 Milk, nonfat solids-baby food/in 0.300000 1.000 0.400 dicamb

 Full comment: dicamba

3600224000 36 Milk, water 0.300000 1.000 0.400 dicamb

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3600224001 36 Milk, water-babyfood/infant form 0.300000 1.000 0.400 dicamb

 Full comment: dicamba

8601000000 86A Water, direct, all sources 0.100000 1.000 0.400 

8602000000 86B Water, indirect, all sources 0.100000 1.000 0.400 

9500177000 O Grape, leaves 1.000000 1.000 0.400 diuron

9500178000 O Grape, raisin 1.000000 4.300 0.400 diuron

9500188000 O Hop 0.050000 1.000 0.400 2,4-D;

 Full comment: 2,4-D;trifluralin

9500235000 O Olive 1.000000 1.000 0.400 diuron

9500236000 O Olive, oil 1.000000 1.000 0.400 diuron

9500263000 O Peanut 0.500000 1.000 0.400 metola

 Full comment: metolachlor

9500264000 O Peanut, butter 0.500000 1.890 0.400 metola

 Full comment: metolachlor

9500265000 O Peanut, oil 0.500000 1.000 0.400 metola

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9500289000 O Pomegranate 0.200000 1.000 0.400 glypho

 Full comment: glyphosate