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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF

CHEMICAL SAFETY AND

POLLUTION PREVENTION

MEMORANDUM

Date: 15-MAY-2013

SUBJECT: Propamocarb Hydrochloride (Propamocarb-HCl). Section 3 Request for use 

on Lima Beans (Succulent). Human-Health Risk Assessment. 

PC Code: 119302 (propamocarb-HCl)

119301 (propamocarb)

DP Barcode: D367968

Decision No.: 402658 Registration No.: 264-678

Petition No.: 2E8072 Regulatory Action: Section 3 Registration

Risk Assessment Type: Single Chemical Aggregate Case No.: 3124

TXR No.: NA CAS No.: 25606-41-1 (propamocarb-HCl)

24579-73-5 (propamocarb)

MRID No.: NA 40 CFR: §180.499

FROM: Jennifer R. Tyler, Chemist

George F. Kramer, Ph.D., Senior Chemist

Kelly M. Lowe, Senior Environmental Scientist 

Anwar Y. Dunbar, Ph.D., Pharmacologist

Risk Assessment Branch 1 (RAB1)/Health Effects Division (HED; 7509P)

THROUGH: Dana M. Vogel, Acting Branch Chief, RAB1

Associate Division Director, HED (7509P)

TO: Barbara Madden, Risk Manager 05

Registration Division (RD; 7575P)

The HED of the Office of Pesticide Programs (OPP) is charged with estimating the risk to human 

health from exposure to pesticides. The RD of OPP has requested that HED evaluate hazard and 

exposure data and conduct dietary, occupational, residential and aggregate exposure assessments, 

as needed, to estimate the risk to human health that will result from the following: 1) the 

proposed Section 3 request for the use of the active ingredient (ai) propamocarb-HCl [propyl N-

[3-(dimethylamino)propyl]carbamate hydrochloride] on succulent lima beans; and 2) existing 

uses on field-grown and greenhouse-grown ornamentals, for which recent revisions have been 

made to the registered labels to amend issues with application rates. A summary of the findings 

and an assessment of human-health risk resulting from all registered and proposed uses are 

provided in this document. The risk assessment and dietary exposure assessment were provided 

by Jennifer Tyler (RAB1); the residue chemistry data review by George Kramer and Jennifer 

Tyler (RAB1); the hazard characterization and endpoint selection by Anwar Dunbar (RAB1); the 

occupational and residential exposure assessment by Kelly Lowe (RAB1); and the drinking 

water exposure assessment by Mohammed A. Ruhman of the Environmental Fate and Effects 

Division (EFED).
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TABLE OF CONTENTS

1.0 Executive Summary............................................................................................................. 3

2.0 HED Recommendations....................................................................................................... 6

2.1 Data Deficiencies ............................................................................................................. 6

2.2 Tolerance Considerations................................................................................................. 7

2.3 Label Recommendations.................................................................................................. 8

3.0 Introduction.......................................................................................................................... 8

3.1 Chemical Identity ............................................................................................................. 8

3.2 Physical/Chemical Characteristics................................................................................... 8

3.3 Pesticide Use Pattern........................................................................................................ 8

3.4 Anticipated Exposure Pathways..................................................................................... 11

3.5 Consideration of Environmental Justice ........................................................................ 12

4.0 Hazard Characterization and Dose-Response Assessment................................................ 12

4.1 Toxicology Studies Available for Analysis ................................................................... 12

4.2 Absorption, Distribution, Metabolism, & Elimination (ADME)................................... 13

4.3 Summary of Toxicological Effects ................................................................................ 13

4.4 Safety Factor for Infants and Children (FQPA SF)........................................................ 14

4.5 Toxicity Endpoint and Point of Departure Selections.................................................... 15

5.0 Dietary Exposure and Risk Assessment ............................................................................ 17

5.1 Residues of Concern Summary and Rationale............................................................... 18

5.2 Food Residue Profile...................................................................................................... 18

5.3 Water Residue Profile .................................................................................................... 19

5.4 Dietary Risk Assessment................................................................................................ 19

6.0 Residential (Non-Occupational) Exposure/Risk Characterization .................................... 20

6.1 Residential Handler Exposure........................................................................................ 20

6.2 Post-Application Exposure............................................................................................. 20

6.3 Residential Risk Estimates for Use in Aggregate Assessment ...................................... 21

6.4 Residential Bystander Post-application Inhalation Exposure ........................................ 21

6.5 Spray Drift...................................................................................................................... 21

7.0 Aggregate Exposure/Risk Characterization....................................................................... 22

7.1 Acute Aggregate Risk .................................................................................................... 22

7.2 Short-Term Aggregate Risk ........................................................................................... 22

7.3 Chronic Aggregate Risk................................................................................................. 23

8.0 Cumulative Exposure/Risk Characterization..................................................................... 23

9.0 Occupational Exposure/Risk Characterization .................................................................. 24

9.1 Occupational Handler Exposure/Risk Estimates............................................................ 24

9.2 Occupational Post-application Exposure/Risk Estimates .............................................. 29

10.0 References.......................................................................................................................... 30

Appendix A. Toxicology Profile Tables...................................................................................... 32

Appendix B. Physical/Chemical Properties................................................................................. 38
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1.0 Executive Summary

Propamocarb is a carbamate fungicide that interferes with fungal synthesis of phospholipids and 

fatty acids. Bayer CropScience currently has a single end-use product of propamocarb-HCl that 

is registered for use on food/feed crops in the U.S. This 6 pounds (lb)/gallon (gal) flowableconcentrate (FlC) formulation (EPA Reg. No. 264-678) is registered for the control of fungal 

diseases on lettuce, potatoes, fruiting vegetables, and cucurbit vegetables. It is approved for 

multiple broadcast foliar applications to the above crops using ground or aerial equipment at 

0.45-1.5 lb active ingredient (ai)/acre (A)/application for a maximum of 4.5-6.0 lb ai/A/season. 

Preharvest intervals (PHIs) range from 0-14 days. Permanent tolerances have been established 

for residues of propamocarb-HCl in/on the above crops at levels ranging from 0.06 ppm in/on 

potatoes to 90 ppm in/on leaf lettuce [40 CFR §180.499 (a)]. There are no proposed residential 

uses at this time; however, there are registered uses for golf course turf which may result in 

residential post-application exposure.

The Interregional Research Project No. 4 (IR-4) has submitted a petition proposing the use of the 

above 6 lb/gal FlC formulation of propamocarb-HCl on succulent lima beans grown east of the 

Rocky Mountains. The proposed use is for up to four broadcast foliar applications at 1.5 lb 

ai/A/application, with a minimum 7-day retreatment interval (RTI), for a maximum of 6.0 lb 

ai/A/season. The minimum PHI is 12 hours after application (0-day). Applications can be made 

using aerial or ground equipment, or by chemigation. In conjunction with this use, IR-4 is 

proposing a 2.0 ppm permanent tolerance with a geographical restriction for residues of 

propamocarb in/on bean, lima, succulent.

In addition to the proposed new use on succulent lima beans, this risk assessment includes a 

reassessment of occupational exposure resulting from existing uses on field-grown and 

greenhouse-grown ornamentals. Recent revisions have been made to the registered labels to 

amend issues with application rates.

Hazard Assessment: The hazard database for propamocarb-HCl is complete. Since the last risk 

assessment, HED’s Hazard Assessment and Policy Committee (HASPOC) evaluated all existing 

hazard and exposure data, and current use patterns for propamocarb-HCl, and used a weight-ofevidence approach to waive the requirement for a subchronic inhalation toxicity study.

Propamocarb-HCl is categorized as having low acute toxicity via the oral, dermal, and inhalation 

routes (Toxicity Categories III-IV). It is not a dermal irritant or a dermal sensitizer. It is 

considered a slight eye irritant.

In all species, decreased body weights, body-weight gains, and food consumption were observed 

for subchronic and chronic durations. Effects throughout the database are indicative of toxicity

to the digestive and gastrointestinal (GI) tracts, specific regions of the nervous system, the eye, 

and to a lesser degree the respiratory tract. In mice, decreased absolute body weights and bodyweight gains were the only effect observed. In rats, there were also signs of neurotoxicity in 

addition to decreased body weights. Decreased motor activities in females occurred following 

acute exposure. Vacuolization of the choroid plexus (ventricles of the brain that produce 

cerebral spinal fluid) was observed for both subchronic and chronic durations. Ocular effects in 

the rat occurred as well, including opacity of the eye and yellow colored eyes in females 

following chronic dietary exposure. In dogs, there were notable effects in the digestive and GI 

tracts, in addition to decreased body weights, evidenced by chronic erosive gastritis, and 

vacuolization of the salivary glands, stomach, and duodenum. There were also respiratory
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effects including vacuolization of the cells of the trachea and lung. There were ocular effects 

including vacuolization of the lacrimal gland, retinal degeneration, and hyporeflectivity of the 

fundus (inner eye tissue below the lens). Dermal toxicity in rats and rabbits consisted of local 

effects including scabs, erythema maculate, focal erythema, necrosis, and ulcerative 

inflammation in the treated skin of females. No systemic effects were observed.

There was no increased quantitative pre-natal sensitivity due to propamocarb-HCl treatment. 

There were however fetal effects at doses which caused maternal toxicity. Effects in the rat 

included increased fetal death and post-implantation loss, increases in minor skeletal anomalies, 

and increased incidences of small fetus. There was also inter-atrial septal defects, and 

hemorrhage in the ears, upper GI tract, and nasopharynx/sinuses. Maternal effects consisted of 

decreased absolute body weights, body-weight gains and food consumption, and mortality. In 

rabbits, the only developmental effect was an increase in post-implantation loss. Maternal 

effects consisted of increased abortions, and body-weight decrements. 

In the rat two-generation reproduction studies, parental and offspring effects occurred at the 

same dose. Parental effects were similar to the effects observed in the rat subchronic and chronic 

studies in addition to clinical signs including salivation, reddish material around the mouth, and 

urine staining. Offspring effects consisted of pup deaths, decreased viability and lactation 

indices and litter size, and decreased pup body weights and body-weight gains. Reproductive 

effects consisted of increased vacuolization and decreased weight of the epididymides, decreased 

sperm counts and motility, and abnormal sperm morphology. In the guideline immunotoxicity

study, effects at the high dose included decreased body-weight gain and decreased food 

consumption. 

In accordance with the EPA Draft Guidelines for Carcinogen Risk Assessment (July, 1999), the 

Hazard Identification Assessment Review Committee (HIARC) classified propamocarb-HCl as 

"not likely to be carcinogenic to humans" by all routes of exposure based upon lack of evidence 

of carcinogenicity in rats and mice. 

Food Quality Protection Act (FQPA) Decision: The RAB1 risk assessment team recommends 

that the FQPA Safety Factor (SF) be reduced to 1X for all exposure scenarios. This decision was 

based on the following (see Section 4.2 for more detail):

 The existing toxicology database for propamocarb-HCl is adequate for FQPA SF 

evaluation. The following acceptable studies are available: developmental toxicity studies 

in rats and rabbits (4); two-generation reproduction studies in rats (2); and acute (2) and 

subchronic (2) neurotoxicity studies.

 There are two guideline acute neurotoxicity studies and two subchronic neurotoxicity

studies for propamocarb-HCl and the effects are well characterized. The endpoints

selected are protective of these effects.

 There is no evidence of increased quantitative susceptibility of rat and rabbit fetuses to in 

utero exposure to propamocarb-HCl. There are qualitative effects observed however in 

both studies. In one of the two-generation reproduction studies, there is an increase in 

pup mortality at doses that cause parental toxicity. The level of concern (LOC) for all of 

these effects is low because: (1) the effects are well-characterized, (2) clear no-observedadverse-effect levels (NOAELs) were established, and (3) the developmental rabbit and 

rat two-generation reproduction studies are being used in endpoint selection.

 There are no residual uncertainties in the exposure database.
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Residue Chemistry and Drinking Water Assessments: The residue chemistry and drinking 

water databases are adequate to assess potential human exposure to propamocarb. Adequate 

residue chemistry data have been submitted to support the proposed use on succulent lima beans. 

EFED provided estimated drinking water concentrations (EDWCs) for surface water [using Tier 

II Pesticide Root Zone Model/Exposure Analysis Modeling System (PRZM/EXAMS)] and 

groundwater [using Screening Concentration in Ground Water (SCI-GROW)] for propamocarb.

Dietary (Food and Drinking Water) Exposure Assessment: Acute and chronic dietary (food 

and drinking water) exposure and risk analyses were conducted for the general U.S. population 

and various population subgroups using the Dietary Exposure Evaluation Model software with 

the Food Commodity Intake Database (DEEM-FCID; Ver. 3.16). For acute and chronic dietary

risk estimates, HED’s LOC is for estimates that exceed 100% of the acute population-adjusted 

dose (aPAD) or chronic population-adjusted dose (cPAD), respectively. The acute and chronic

dietary exposure assessments were unrefined [assuming tolerance-level residues and assuming 

100% crop treated (CT) for all registered and proposed commodities]. The results indicate that 

the acute (95th percentile) and chronic dietary exposure estimates are below HED’s LOC for the 

general U.S. population and all other population subgroups. For both acute and chronic 

assessments, the most highly exposed population subgroup is all infants <1 year old at 75% of 

the aPAD and 50% of the cPAD, respectively. 

Residential (Non-Occupational) Exposure Assessment: Residential exposures are not anticipated 

from the proposed use on lima beans. There is a registered use of propamocarb on golf courses, 

and residential exposure from that use has been reassessed using the 2012 Residential Standard 

Operating Procedures (SOPs). Residential handler exposure is not anticipated, but there is the 

potential for residential post-application dermal exposure. Chemical-specific turf-transferable 

residue (TTR) data are available for propamocarb and were used in the residential post-application 

exposure assessment. The residential post-application dermal exposure and risk estimates for 

golfers indicate that short-term margins of exposure (MOEs) are not of concern to HED (i.e., 

MOEs ≥ 100) on the day of application. Dermal MOEs ranged from 280 for children 6 to <11 

years old to 380 for adults.

Aggregate Exposure Scenarios and Risk Conclusions: For the proposed uses, human-health 

aggregate risk assessments have been conducted for the following exposure scenarios: acute 

aggregate exposure (food + drinking water), short-term aggregate exposure (food + drinking 

water + residential), and chronic aggregate exposure (food + drinking water). An intermediateterm assessment was not conducted as intermediate-term residential exposures are not expected 

based on the current use patterns. However, as the short- and intermediate-term points of 

departure (PODs) are the same, the short-term aggregate is protective of any potential 

intermediate-term exposures. A cancer aggregate risk assessment was not performed because 

propamocarb-HCl is not carcinogenic. All potential exposure pathways were assessed in the 

aggregate risk assessment as a conservative, health-protective measure. All aggregate risk 

estimates are not of concern to HED for the scenarios listed above. 

Occupational Handler and Post-application Exposure Estimates: Occupational short- and 

intermediate-term dermal and inhalation handler exposures are expected for individuals involved 

in applications of propamocarb-HCl to succulent lima beans (proposed use) and commerciallygrown field and greenhouse ornamentals (registered use). For the proposed succulent lima beans 

use, HED has determined that risk estimates are not of concern (i.e., MOE >100) with baseline 

attire. For the existing use on commercially grown field and greenhouse ornamentals, HED has
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determined that risks are not of concern (i.e., MOE >100) with baseline attire and chemicalresistant gloves (as required on the label).

Occupational short- and intermediate-term dermal post-application exposures are expected for 

individuals reentering lima bean fields treated with propamocarb. HED has determined that the 

risk estimates are not of concern to HED (i.e., MOEs ≥ 100) on the day of application. The 

revised labels for the ornamental uses indicate all applications are to be soil/ground-directed; 

therefore, post-application exposure to residues on foliage is not expected and a quantitative 

post-application assessment was not conducted.

Based on the Agency's current practices, a quantitative non-cancer occupational post-application 

inhalation exposure assessment was not performed for propamocarb at this time. If new policies 

or procedures are put into place, the Agency may revisit the need for a quantitative occupational 

post-application inhalation exposure assessment for propamocarb. For the greenhouse 

ornamental uses, the Worker Protection Standard (WPS) for Agricultural Pesticides contains 

requirements for protecting workers from inhalation exposures during and after greenhouse 

applications through the use of ventilation requirements [40 CFR 170.110, (3) (Restrictions 

associated with pesticide applications)]. The 12-hour restricted entry interval (REI) is adequate 

for the proposed use patterns.

Review of Human Research: This risk assessment relies in part on data from studies in which 

adult human subjects were intentionally exposed to a pesticide or other chemical. These data, 

which include studies from Pesticide Handlers Exposure Database Version 1.1 (PHED 1.1); 

Agricultural Handler Exposure Task Force (AHETF) database; the Outdoor Residential 

Exposure Task Force (ORETF) database; and Agricultural Reentry Task Force (ARTF) database, 

are subject to ethics review pursuant to 40 CFR 26, have received that review, and are compliant 

with applicable ethics requirements. For certain studies, that review may have included review 

by the Human Studies Review Board. Descriptions of data sources as well as guidance on their 

use can be found at http://www.epa.gov/pesticides/science/handler-exposure-data.html and 

http://www.epa.gov/pesticides/science/post-app-exposure-data.html.

2.0 HED Recommendations

HED concludes that the toxicological, residue chemistry and occupational/residential databases 

support a Section 3 registration and establishment of the tolerances listed in Section 2.2.2. HED 

is recommending for additional data in conjunction with this petition as listed in Section 2.1.

2.1 Data Deficiencies

2.1.1 Residue Chemistry

OPPTS GLN 860.1650: An analytical standard for propamocarb is not currently available in the 

EPA National Pesticide Standards Repository [personal communication with T. Cole, Analytical 

Chemistry Branch (ACB), 9/5/12]. An analytical reference standard of propamocarb should be 

supplied and replenished as requested by the Repository. The reference standard should be sent 

to the Analytical Chemistry Lab, which is located at Fort Meade, to the attention of Theresa Cole 

at the following address:
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USEPA

National Pesticide Standards Repository/Analytical Chemistry Branch/OPP

701 Mapes Road

Fort George G. Meade, MD 20755-5350

(Note that the mail will be returned if the extended zip code is not used.)

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

An adequate gas chromatography/nitrogen-phosphorus detection (GC/NPD) method (Analytical 

Method No. XAM-34) is available for enforcing tolerances on plant commodities. This method 

has undergone successful independent laboratory validation (ILV) and petition method validation 

(PMV) trials (Memo, J. Rowell, 3-OCT-2000; D268955). The method has been sent to the Food 

and Drug Administration (FDA) and is currently listed in the Pesticide Analytical Method 

(PAM) Vol. II for determining residues of propamocarb in plant commodities. The limit of 

quantitation (LOQ) for this method is 0.05 ppm.

Adequate multiresidue method testing data are available for propamocarb and these data have 

been forwarded to FDA for evaluation (Memo, J. Rowell, 15-MAY-2000; D266084). Parent 

compound was not recovered by any of the FDA multiresidue methods.

2.2.2 Recommended Tolerances

Table 2.2.3. Tolerance Summary for Propamocarb.

Commodity Proposed Tolerance 

(ppm)

HED-Recommended 

Tolerance (ppm)

Comments;

Correct Commodity Definition

40 CFR §180.499(c)1

Bean, lima, succulent 2.0 2.0

1 As the proposed tolerance is geographically restricted to regions east of the Rocky Mountains, the tolerance should be listed under 40 CFR 

§180.499(c).

2.2.3 Revisions to Petitioned-For Tolerances

The residue chemistry data support a tolerance with a geographical restriction for residues of 

propamocarb in/on beans, lima, succulent at 2.0 ppm.

Note to RD: HED recommends the following revision to the tolerance expression to (1) clarify

that, as provided in FFDCA section 408(a)(3), the tolerance covers metabolites and degradates of 

propamocarb not specifically mentioned; (2) clarify that compliance with the specified tolerance 

levels is to be determined by measuring only the specific compounds mentioned in the tolerance 

expression; and (3) to harmonize with the codex maximum residue limit (MRL) expression:

"Tolerances are established for residues of propamocarb, including its metabolites and 

degradates, in or on the commodities listed below resulting from the application of the 

hydrochloride salt of propamocarb. Compliance with the following tolerance levels is to 

be determined by measuring only propamocarb (propyl N-[3-

(dimethylamino)propyl]carbamate)."
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2.2.4 International Harmonization

There are currently no established Codex, Canadian, or Mexican MRLs for propamocarb on lima 

beans. Therefore, harmonization of MRLs and U.S. tolerances is not an issue at this time. 

2.3 Label Recommendations

HED is not recommending for any changes to the proposed Previcur®Flex Fungicide (EPA Reg. 

No. 264-678) label.

3.0 Introduction

3.1 Chemical Identity

Table 3.1. Propamocarb Nomenclature.

Compound

Common name Propamocarb HCl

Company experimental name AE B066752

IUPAC name Propyl 3-(dimethylamino) propylcarbamate hydrochloride

CAS name Propyl 3-[(dimethylamino) propyl]carbamate monohydrochloride

CAS registry number 25606-41-1 (propamocarb-HCl)

24579-73-5 (propamocarb)

End-use product (EP) 6.0 lb/gal FlC (Previcur®Flex Fungicide; EPA Reg No. 264-678)

Chemical Class Carbamate

3.2 Physical/Chemical Characteristics

The physical and chemical properties, as well as a summary of relevant environmental fate 

parameters are detailed in Appendix B. Propamocarb-HCl is relatively non-persistent. It is 

stable to photodegradation in water and is photodegradable on soil with a half-life of 35 days. 

Propamocarb degrades fairly rapidly by microbial-mediated metabolism and is persistent to 

anaerobic metabolism. It dissipates rapidly under field conditions, and has variable mobility

(from mobile to relatively immobile). Propamocarb-HCl has a low vapor pressure (10-7 mmHg)

and, therefore, is unlikely to volatilize. The low Henry's law constant (6.5 x 10-13atm m3/mole) 

also indicates that it has a low potential of volatizing from water (Memo, Olga M. Odiott, 15-

JUL-1995).

3.3 Pesticide Use Pattern

Lima Beans (Proposed Use): IR-4 has proposed the use of propamocarb-HCl for the control of 

downy mildew and Pythium root rots and seedling diseases on succulent lima beans grown east 

of the Rocky Mountains. Propamocarb-HCl, formulated as Previcur®Flex Fungicide (EPA Reg. 

No. 264-678), may be applied using aerial, ground or chemigation equipment. The proposed 

propamocarb label for the use on succulent lima beans direct applicators and other handlers to 

wear long-sleeved shirt and long pants, chemical-resistant gloves made of any waterproof 

material such as polyethylene or polyvinyl chloride, and shoes plus socks. An example label 

N

H3C

N

H

O

CH3

CH3

O

HCl
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containing use directions for lima beans was provided, and is summarized below in Table 3.3.1.

Table 3.3.1. Summary of Directions for Proposed Use of Propamocarb-HCl on Succulent Lima Beans.

Application Timing, 

Type, and 

Equipment1

Formulation

[EPA Reg. 

No.]

App. Rate

(lb ai/A)

Max. No. 

App. per 

Season

Max. Seasonal 

App. Rate

(lb ai/A)

PHI

(days)

Use Directions and 

Limitations2

Lima beans (For Use East of the Rocky Mountains Only)

Broadcast foliar 

applications under 

favorable disease 

conditions; ground or 

aerial equipment

6.0 lb/gal FlC

[264-678]

1.5 4 6.0 0

3 A minimum 7-day RTI is 

specified.

Apply in a minimum volume of 

5 and 15 gal/A using aerial and 

ground equipment, respectively.

1. Applications can also be made by irrigation: transplant watering, drip irrigation or sprinklers.

2. The label lists the following rotational crop restrictions: Do not rotate to root and leafy vegetables for 30 days, and do not rotate to winter 

wheat or other non-labeled crops for 120 days.

3. Do not harvest lima beans within 12 hours of application. The REI is also 12 hours.

The submitted use directions are sufficient to allow for evaluation of the submitted residue data 

relative to the proposed use patterns. The available field trial data support the proposed use 

directions for succulent lima beans.

Commercially Grown Field and Greenhouse Ornamentals (Existing Use): In addition to the 

proposed use on succulent lima beans, an occupational exposure assessment was conducted for 

an existing use of propamocarb-HCl on field-grown and greenhouse-grown ornamentals to 

address recent revisions to product labels. Applications are made using a variety of equipment, 

including groundboom, backpack sprayer, mechanically pressurized handgun sprayer, and 

dipping of the bare root plant. The use directions for the existing uses on ornamentals are 

summarized in Table 3.3.2.

Table 3.3.2. Summary of Directions for Existing Use of Propamocarb-HCl on Ornamentals.

Application Timing, Type, 

and Equipment

Formulation 

[EPA Reg. 

No.]

App 

Rate (lb 

ai/A)

Max. No. 

App. per 

Season

Max 

Seasonal 

App Rate

(lb ai/A)

PHI

(days)

Use Directions 

and Limitations

Ornamentals (commercially grown in greenhouses and container grown in nurseries)

Seeding and 

Transplanting 

area

Groundboom, 

Mechanicallypressurized 

handgun, 

Backpack 

sprayer, Dip

Banol®

EPA Reg. 

No. 432-942 

SC, 6 lb 

ai/gal

0.014 lb 

ai/gal

46 lb 

ai/A

no more 

than 2 

apps/season

128 NA

RTI = 7 days to 6 

months

REI = 24 hours

Do not apply 

through any type 

of irrigation 

system. Do not 

use on field 

grown 

ornamentals. 

Apply by soildirected drench 

only. Do not 

apply soil drench 

to foliage.

Cutting bed 

(transplants; 

drench 

application)

Mechanicallypressurized 

handgun, 

Backpack 

sprayer, Dip

0.009 lb 

ai/gal

82 lb 

ai/A

no more 

than 2 apps/ 

season; if 2 

apps made, 

max rate per 

app = 31.5 fl 

oz/1000 sq 

ft = 64 lb 

ai/A

Potting (dip 

bare root plant 

and drench 

pots)

Mechanicallypressurized 

handgun, 

Backpack 

sprayer, Dip

0.009 lb 

ai/gal

64 lb 

ai/A

no more 

than 2 

apps/season
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Table 3.3.2. Summary of Directions for Existing Use of Propamocarb-HCl on Ornamentals.

Application Timing, Type, 

and Equipment

Formulation 

[EPA Reg. 

No.]

App 

Rate (lb 

ai/A)

Max. No. 

App. per 

Season

Max 

Seasonal 

App Rate

(lb ai/A)

PHI

(days)

Use Directions 

and Limitations

Seeding and 

Transplanting 

area

Groundboom, 

Mechanicallypressurized 

handgun, 

Backpack 

sprayer, Dip Proplant Turf 

and 

Ornamental 

Fungicide

EPA Reg. 

No. 55260-9

SC, 6 lb 

ai/gal

0.014 lb 

ai/gal

46 lb 

ai/A

no more 

than 2 apps/ 

season; if 2 

apps made, 

max rate per 

app = 31.5 fl 

oz/1000 sq 

ft = 64 lb 

ai/A

128 NA

RTI = 7 days to 6 

months

REI = 24 hours

Do not apply 

through any type 

of irrigation 

system. Apply by 

soil-directed 

drench only. 

Maximum single 

application rate 

must be <82 lb 

ai/A. Foliar 

applications to 

ornamentals 

grown for cut 

flowers are 

prohibited.

Cutting bed 

(transplants; 

drench 

application)

Mechanicallypressurized 

handgun, 

Backpack 

sprayer, Dip

0.009 lb 

ai/gal

82 lb 

ai/A

Potting (dip 

bare root plant 

and drench 

pots)

Mechanicallypressurized 

handgun, 

Backpack 

sprayer, Dip

0.009 lb 

ai/gal

64 lb 

ai/A

Seeding and 

Transplanting 

area

Groundboom, 

Mechanicallypressurized 

handgun, 

Backpack 

sprayer, Dip Advan 

Propamocarb

EPA Reg. 

No. 83070-8

SC, 6 lb 

ai/gal

0.014 lb 

ai/gal

46 lb 

ai/A

no more 

than 2 apps/

year

128 NA

RTI = 3 - 6 week 

intervals

REI = 12 hours

Do not apply 

through any type 

of irrigation 

system. Drench 

applications must 

be limited to soil 

directed sprays. 

Foliar

applications to 

ornamentals 

grown for cut 

flowers are 

prohibited.

Cutting bed 

(transplants; 

drench 

application)

Mechanicallypressurized 

handgun, 

Backpack 

sprayer, Dip

0.009 lb 

ai/gal

82 lb 

ai/A

Potting (dip 

bare root plant 

and drench 

pots)

Mechanicallypressurized 

handgun, 

Backpack 

sprayer, Dip

0.009 lb 

ai/gal

82 lb 

ai/A*
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Table 3.3.2. Summary of Directions for Existing Use of Propamocarb-HCl on Ornamentals.

Application Timing, Type, 

and Equipment

Formulation 

[EPA Reg. 

No.]

App 

Rate (lb 

ai/A)

Max. No. 

App. per 

Season

Max 

Seasonal 

App Rate

(lb ai/A)

PHI

(days)

Use Directions 

and Limitations

Woody ornamentals

Drench 

application

Mechanicallypressurized 

handgun, 

Backpack 

sprayer

Banol®

EPA Reg. 

No. 432-942

SC, 6 lb 

ai/gal

0.012 lb 

ai/gal

64 lb 

ai/A

no more 

than 2 apps/ 

season; if 2 

apps made, 

max rate per 

app = 31.5 fl 

oz/1000 sq 

ft = 64 lb 

ai/A

128

NA

432-942: RTI = 7 

days to 6 months 

and REI = 24 

hours

55260-9 and 

83070-8: RTI = 3 

- 4 months and 

REI = 12 hours

Proplant Turf 

and 

Ornamental 

Fungicide

EPA Reg. 

No. 55260-9

SC, 6 lb 

ai/gal

no more 

than 2 apps/ 

season; 

maximum 

single app 

rate must be 

<82 lb ai/A

NA

Advan 

Propamocarb

EPA Reg. 

No. 83070-8

SC, 6 lb 

ai/gal

no more 

than 2 

apps/season

NA

3.4 Anticipated Exposure Pathways

RD has requested an assessment of human health risk to support the proposed new use of 

propamocarb-HCl on succulent lima beans. Humans may be exposed to propamocarb in food 

and drinking water, since it may be applied directly to growing crops and application may result 

in propamocarb reaching surface and ground water sources of drinking water. There are no 

residential uses associated with the proposed use; however, as propamocarb-HCl is currently 

registered for use on golf courses, human exposure in residential or non-occupational settings 

may occur. In an occupational setting, applicators may be exposed while handling the pesticide 

prior to application, as well as during application to lima beans. In addition, there is a possibility

of post-application dermal exposure to occupational workers when reentering field previously

treated with propamocarb-HCl.

The current risk assessment considers all of the aforementioned exposure pathways based on the 

proposed new uses of propamocarb-HCl, but also considers the existing uses as well, particularly 

for the dietary and residential exposure assessments. The most recent human-health risk 

assessment was conducted in 2004 in conjunction with a Section 3 request for the use of 

propamocarb-HCl on lettuce, fruiting vegetables, and cucurbit vegetables (Memo, J. Tyler, et al.; 

20-FEB-2004; D284504). 
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3.5 Consideration of Environmental Justice

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

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

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

(http://www.hss.energy.gov/nuclearsafety/env/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, HED estimates risks to population 

subgroups from pesticide exposures that are based on patterns of that subgroup’s food and water 

consumption, and activities in and around the home that involve pesticide use in a residential 

setting. Extensive data on food consumption patterns are compiled by the U.S. Department of 

Agriculture (USDA) under the National Health and Nutrition Examination Survey, What We Eat 

in America, (NHANES/WWEIA; 2003-2008) 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.

4.0 Hazard Characterization and Dose-Response Assessment

4.1 Toxicology Studies Available for Analysis

There are two data sets for propamocarb-HCl (Memo, G. Reddy et al., 12-OCT-2005, TXR 

#0052538), the second of which was not accounted for in the previous risk assessment (Memo, J. 

R-Tyler et al., 20-FEB-2004, D284504). The first set was sponsored by Bayer Crop 

Sciences/NOR-AM Agricultural Products (Naperville, Ill.). The second set was sponsored by 

Chimac-Agriphar s.a. (Ougrée, Belgium) in support of an import tolerance. This second set of 

studies did not change the endpoints from the 2004 risk assessment.

Since the last risk assessment, a guideline immunotoxicity study has been submitted and 

reviewed. The hazard database for propamocarb hydrochloride is therefore complete. 

Since the last risk assessment, HED’s HASPOC evaluated all existing hazard and exposure data, 

and current use patterns for propamocarb-HCl, and used a weight-of-evidence approach to waive 

the requirement for a subchronic inhalation toxicity study (Memo, J. Van Alstine, 14-FEB-2013; 

TXR#0056466). This weight-of-evidence approach for waiving the inhalation study considered: 

1) there was no evidence of toxicity to the respiratory tract following inhalation exposure in two 

acute inhalation studies (no lung pathology) to indicate a concern for toxicity via repeated 

exposure; 2) in a repeated exposure inhalation study with a structural analog (bendiocarb), there 

were no clinical signs associated with respiratory tract toxicity and alveolar macrophages of the 

lungs were seen only at the highest concentration tested; 3) there was no target organ toxicity 

following oral exposures; only generalized toxicity (decreases in body weigh/body-weight gain 
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and food consumptions were seen in mice, rats, and dogs; and 4) the use of an oral POD results 

in a MOE of 6100 mixing/loading activities for chemigation applications in green houses.

4.2 Absorption, Distribution, Metabolism, & Elimination (ADME)

Greater than 80% of propamocarb was excreted in the urine 24 hours post dosing, suggesting that 

it was well absorbed from the GI tract. Excretion was rapid with the majority of the 

administered doses eliminated and recovered within six hours following single dosing, and 24 

hours following repeated dosing. Pharmacokinetics parameters for both blood and plasma were 

Cmax = 0.20-0.25 μg equiv./g, Tmax = 0.50-0.88 h, and T1⁄2 = 1.7-2.9 h in all animals. At 6 hours 

post dosing, propamocarb was detectable in the blood, skin, liver, lungs, kidneys, ovaries, and 

adrenals. At 24 hours post dosing, radioactivity was detectable only in the liver and the kidney, 

and three weeks following the cessation of treatment, it was undetectable in any tissue. In the 

low-dose group, the predominant metabolite was carbonyl propamocarb, and in the high-dose 

group, the major metabolite was 3-hydroxypropyl propamocarb.

4.2.1 Dermal Absorption

There is no dermal-penetration study available for propamocarb-HCl. Dermal absorption was 

estimated by comparing the rabbit maternal toxicity lowest-observed-adverse-effect level 

(LOAEL) (300 mg/kg/day) from the rabbit developmental toxicity study with the LOAEL (525 

mg/kg/day) from the 21-day rabbit dermal study. The dermal-absorption factor is: 300 

mg/kg/day  525 mg/kg/day × 100 = 60%.

4.3 Summary of Toxicological Effects

Propamocarb-HCl was categorized as having low acute toxicity via the oral, dermal, and 

inhalation routes (Toxicity Categories III-IV). It is not a dermal irritant or a dermal sensitizer. It 

is considered a slight eye irritant.

In all species, decreased body weights, body-weight gains, and food consumption were observed 

for subchronic and chronic durations. Effects throughout the database are indicative of toxicity

to the digestive and GI tracts, specific regions of the nervous system, the eye, and to a lesser 

degree the respiratory tract. In mice, decreased absolute body weights and body-weight gains 

were the only effect observed. In rats, there were also signs of neurotoxicity in addition to the 

decreased body weights. Decreased motor activities in females occurred following acute 

exposure. Vacuolization of the choroid plexus (ventricles of the brain that produce cerebral 

spinal fluid) was observed for both subchronic and chronic durations. Ocular effects in the rat 

occurred as well, including opacity of the eye and yellow colored eyes in females following 

chronic dietary exposure. In dogs, there were also notable effects in the digestive and GI tracts, 

in addition to decreased body weights, evidenced by chronic erosive gastritis, and vacuolization 

of the salivary glands, stomach, and duodenum. There were also respiratory effects including 

vacuolization of the cells of the trachea and lung. There were ocular effects including 

vacuolization of the lacrimal gland, retinal degeneration, and hyporeflectivity of the fundus 

(inner eye tissue below the lens). Dermal toxicity in rats and rabbits consisted of local effects 

including scabs, erythema maculate, focal erythema, necrosis, and ulcerative inflammation in the 

treated skin of females. No systemic effects were observed.

There was no increased quantitative pre-natal sensitivity due to propamocarb-HCl treatment. 
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There were however fetal effects at doses which caused maternal toxicity. Effects in the rat 

included increased fetal death and post-implantation loss, increases in minor skeletal anomalies, 

and increased incidences of small fetus. There was also inter-atrial septal defects, and 

hemorrhage in the ears, upper GI tract, and nasopharynx/sinuses. Maternal effects consisted of 

decreased absolute body-weights, body-weight gains and food consumption, and mortality. In 

rabbits, the only developmental effect was an increase in post-implantation loss. Maternal 

effects consisted of increased abortions, and body-weight decrements similar. 

In the rat two-generation reproduction studies, parental and offspring effects occurred at the 

same dose. Parental effects were similar to the effects observed in the rat subchronic and chronic 

studies in addition to clinical signs including salivation, reddish material around the mouth, and 

urine staining. Offspring effects consisted of pup deaths, decreased viability and lactation 

indices and litter size, and decreased pup body weights and body-weight gains. Reproductive 

effects consisted of increased vacuolization and decreased weight of the epididymides, decreased 

sperm counts and motility, and abnormal sperm morphology.

In the guideline immunotoxicity study, effects at the high dose included decreased body-weight

gain and decreased food consumption. 

4.4 Safety Factor for Infants and Children (FQPA SF)

The propamocarb-HCl risk assessment team evaluated the quality of the hazard and exposure 

data and determined that the FQPA SF should be reduced to 1X for all exposure scenarios for the 

following reasons: there is a complete toxicological database, there is no evidence of increased 

quantitative susceptibility in the developing or young animal, and there is no uncertainty in the 

exposure data. The details for reducing the FQPA safety factor to 1X are detailed below.

4.4.1 Completeness of the Toxicology Database

The toxicology database is adequate for characterizing propamocarb-HCl toxicity and 

quantification of hazard for dietary and occupational/residential exposures. 

4.4.2 Evidence of Neurotoxicity

There are two guideline acute neurotoxicity studies and two subchronic neurotoxicity studies for 

propamocarb-HCl and the effects are well characterized. The endpoints selected are protective 

of these effects.

4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal

There is no evidence of increased quantitative susceptibility of rat and rabbit fetuses to in utero

exposure to propamocarb-HCl. There are qualitative effects observed however in both

developmental studies. In one of the two-generation reproduction studies, there is an increase in 

pup mortality at doses that cause parental toxicity. The LOC for all of these effects is low 

because: (1) the effects are well characterized, (2) clear NOAELs were established, and (3) the 

developmental rabbit and rat two-generation reproduction studies are being used in endpoint 

selection.
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4.4.4 Residual Uncertainty in the Exposure Database

The acute and chronic dietary food exposure assessment utilizes existing and proposed 

tolerance-level residues and 100% CT information for all commodities. By using these 

screening-level assessments, actual exposures/risks will not be underestimated.

The dietary drinking water assessment utilizes water concentration values generated by models 

and associated modeling parameters, which are designed to provide conservative, healthprotective, high-end estimates of water concentrations that will not likely be exceeded.

The residential exposure assessment is based upon the residential SOPs, which are based upon 

reasonable worst-case assumptions and are not expected to underestimate risk. 

4.5 Toxicity Endpoint and Point of Departure Selections

4.5.1 Dose-Response Assessment

Acute Dietary Endpoint (females 13-49 years of age): The rabbit developmental toxicity study

(MRID #000072574) was used to select the endpoint for the acute reference dose (aRfD) of 1.5 

mg/kg/day for females 13-49 years of age. The NOAEL is 150 mg/kg/day (developmental). The 

LOAEL of 300 mg/kg/day was based on increased post-implantation loss in rabbits. This 

endpoint is considered appropriate for females of childbearing age (13-49 years old) since the 

effects could occur due to a single in utero exposure. An uncertainty factor of 100 was applied 

to the NOAEL to derive the aRfD for females 13-49 years of age. The FQPA SF of 1X is 

applicable for the acute dietary risk assessment. Thus, the aPAD for females 13-49 years old is 

1.5 mg/kg/day. 

Acute Dietary Endpoint (general population): The rat acute oral neurotoxicity study (MRID 

#43062301) was used to select the endpoint for the aRfD of 2.0 mg/kg/day for the general U.S. 

population (including infants and children). The NOAEL is 200 mg/kg/day. The LOAEL of 

2000 mg/kg/day is based on decreased body-weight gain and decreased motor activity 8 hrs postdosing in females. These effects occurred following a single dose and therefore are appropriate 

for use in the acute dietary risk assessment. An uncertainty factor of 100 was applied to the 

NOAEL to derive the aRfD for the general U.S. population. The FQPA SF of 1X is applicable 

for the acute dietary risk assessment. Thus, the aPAD for the general U.S. population (including 

infants and children) is 2.0 mg/kg/day.

Chronic Dietary Endpoint: The mouse carcinogenicity study (MRID #44693801) was used to 

select the endpoint for establishing the chronic reference dose (cRfD) of 0.12 mg/kg/day. The 

NOAEL is 12 mg/kg/day. The LOAEL of 95 mg/kg/day was based on decreased absolute bodyweight and body-weight gain in females. An uncertainty factor of 100 was applied to the 

NOAEL to derive the cRfD. The FQPA safety factor of 1X is applicable for chronic dietary risk 

assessment. Thus, the cPAD is 0.12 mg/kg/day. This POD is protective of the effects in the 

other species tested observed at higher doses. This study is further protective for the general 

U.S. population for exposure for the chronic duration.

Short- and Intermediate-Term Incidental Oral Endpoint: Short- and intermediate-term incidental 

oral endpoints were selected from the two-generation rat reproduction study. The NOAEL is 

65.41 mg/kg/day. The LOAEL is 406.7 mg/kg/day based upon significant reduction in body

weights of F0 and F1 pups during days 14 - 21 of lactation. This study and endpoint are 
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appropriate for the population of concern (infants and children) and the route and durations of 

exposure.

Short- and Intermediate-Term Dermal Endpoints: Short- and intermediate-term dermal 

endpoints were selected from the rabbit 21-day dermal toxicity study (MRID #00071526). The 

NOAEL is 150 mg/kg/day and the LOAEL of 525 mg/kg/day is based on decreased body-weight

gain in females. This study was selected because the route of exposure is appropriate for the 

exposure scenario as well as the expected durations of exposure in occupational settings. It is 

also protective of the developmental effects in rabbits.

Short- and Intermediate-term Inhalation Endpoint: Short- and intermediate-term inhalation 

endpoints were selected from the two-generation rat reproduction study (MRID #44730103). 

The NOAEL is 65.41 mg/kg/day. The parental LOAEL of 406.7 mg/kg/day is based upon 

significant reduction in body weights in the parental generation. This dose/endpoint is 

appropriate for short- and intermediate-term inhalation exposure for adults in occupational 

settings.

4.5.2 Recommendation for Combining Routes of Exposures for Risk Assessment

Exposures (dermal, oral, and inhalation) can be combined if the toxicological effects are the 

same. Decreased body weight was the endpoint of concern for the incidental oral, dermal and 

inhalation routes for propamocarb. In the two-generation reproduction study used for the 

incidental oral route, body-weight changes were observed in both adults and offspring. 

Therefore, for propamocarb, the dermal, inhalation, and incidental oral routes can be combined 

for risk assessment since a common endpoint was observed.

4.5.3 Cancer Classification and Risk Assessment Recommendation

In accordance with the EPA Draft Guidelines for Carcinogen Risk Assessment (July, 1999), the 

HIARC classified propamocarb-HCl as "not likely to be carcinogenic to humans" by all routes of 

exposure based upon lack of evidence of carcinogenicity in rats and mice, therefore, a cancer risk 

assessment is not required. 

4.5.4 Summary of Points of Departure and Toxicity Endpoints Used in Human Risk 

Assessment

Table 4.5.4.1. Summary of Toxicological Doses and Endpoints for Propamocarb-HCl for Use in Dietary and 

Non-Occupational Human-Health Risk Assessments.

Exposure/ 

Scenario POD

Uncertainty/FQPA 

Safety Factors

RfD, PAD, 

LOC for 

Risk 

Assessment

Study and Toxicological Effects

Acute Dietary 

(Females 13-

49 years of 

age)

NOAEL = 

150 

mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 1X

Acute RfD = 

1.5 mg/kg/day

aPAD = 1.5 

mg/kg/day

Developmental Toxicity Study - Rabbit

Developmental LOAEL = 300 mg/kg/day 

based on increased post-implantation loss.

Acute Dietary

(General U.S. 

population, 

including 

Infants and 

Children)

NOAEL = 

200 

mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 1X

Acute RfD = 

2 mg/kg/day

aPAD = 2 

mg/kg/day

Acute Neurotoxicity Screening Battery -

Rat

LOAEL = 2000 mg/kg/day, based on 

decreased body-weight gain and decreased 

motor activity.
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Table 4.5.4.1. Summary of Toxicological Doses and Endpoints for Propamocarb-HCl for Use in Dietary and 

Non-Occupational Human-Health Risk Assessments.

Exposure/ 

Scenario POD

Uncertainty/FQPA 

Safety Factors

RfD, PAD, 

LOC for 

Risk 

Assessment

Study and Toxicological Effects

Chronic 

Dietary (All 

Populations)

NOAEL = 

12 

mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 1X

Chronic RfD 

= 0.12 

mg/kg/day

cPAD = 0.12 

mg/kg/day

Carcinogenicity Study - Mouse

LOAEL = 95 mg/kg/day, based on 

decreased body-weight and body-weight

gain in females.

Incidental Oral

Short-l (1-30 

days) and 

IntermediateTerm (1-6 

months) 

NOAEL = 

65.41 

mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 1X

Residential 

LOC for 

MOE = 100

2-generation Reproduction Toxicity 

Study - Rat

Offspring LOAEL = 406.7 mg/kg/day, 

based on reduced pup weights in F0 & F1

during Day 14 - 21 of lactation.

Cancer (oral, 

dermal, 

inhalation)

Classification: “not likely to be carcinogenic to humans.”

Point of departure (POD) = A data point or an estimated point that is derived from observed dose-response data and 

used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human 

exposures. NOAEL = no-observed adverse-effect level. LOAEL = lowest-observed adverse-effect level. UF = 

uncertainty factor. UFA = extrapolation from animal to human (interspecies). UFH = potential variation in 

sensitivity among members of the human population (intraspecies). FQPA SF = FQPA Safety Factor. PAD = 

population-adjusted dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of exposure. LOC = level 

of concern. 

Table 4.5.4.2. Summary of Toxicological Doses and Endpoints for Propamocarb-HCl for Use in Occupational 

Human Health Risk Assessments.

Exposure/ Scenario POD Uncertainty 

Factors

LOC for Risk 

Assessment Study and Toxicological Effects

Dermal 

Short- (1-30 days) 

and IntermediateTerm (1-6 months)

NOAEL = 

150 

mg/kg/day

UFA = 10X

UFH = 10X

Occupational 

LOC for MOE 

= 100

21-day Dermal Toxicity Study - Rabbit

LOAEL = 525 mg/kg/day, based on 

decreased body-weight gain in females.

Inhalation 

Short- (1-30 days) 

and IntermediateTerm (1-6 months)

NOAEL = 

65.41 

mg/kg/day

UFA = 10X

UFH = 10X

Occupational 

LOC for MOE 

= 100

Two-generation Reproduction Toxicity 

Study – Rat

Parental LOAEL = 406.69 mg/kg/day for 

males and 467.13 mg/kg/day for females 

based on decreased body weights.

Cancer (oral, dermal, 

inhalation) Classification: “not likely to be carcinogenic to humans”

Point of departure (POD) = A data point or an estimated point that is derived from observed dose-response data and 

used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human 

exposures. NOAEL = no-observed adverse-effect level. LOAEL = lowest-observed adverse-effect level. UF = 

uncertainty factor. UFA = extrapolation from animal to human (interspecies). UFH = potential variation in 

sensitivity among members of the human population (intraspecies). MOE = margin of exposure. LOC = level of 

concern. 

5.0 Dietary Exposure and Risk Assessment 

The residue chemistry data submitted in support of the proposed Section 3 use on succulent lima 

beans were reviewed by HED in a memo dated 15-MAY-2013 (Memo, J. Tyler; D359104). The 

EDWCs were provided by EFED (Memo, M. Ruhman; 11-DEC-2012). The acute and chronic 

dietary exposure assessment was completed in a HED memorandum dated 15-MAY-2013
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(Memo, J. Tyler; D367969).

5.1 Residues of Concern Summary and Rationale

The nature of propamocarb residues in vegetable crops is adequately understood based on the 

available potato, cucumber, and spinach metabolism studies. The residue of concern for both 

risk assessment and tolerance enforcement is propamocarb per se (Memo, J. Rowell, 03-MAY2000; D264293). The nature of the residue in ruminants is adequately understood based on 

acceptable metabolism and feeding studies on dairy cattle, which were submitted as 

propamocarb-HCl is currently registered for use on ruminant feed items. The residues of 

concern in livestock for tolerance and risk assessment purposes are the parent propamocarb and 

the 2-hydroxy propamocarb and propamocarb glucuronide metabolites (Memos, J. Rowell, 03-

MAY-2000, D264293; and J. Tyler, 10-MAR-2005; D304509). No poultry metabolism study

has been submitted. Propamocarb-HCl is currently not registered for use on any poultry feed 

items. However, the results of a poultry feeding study will be required to support any future uses 

that are classified as poultry feed items.

5.2 Food Residue Profile

Adequate residue chemistry data are available for risk assessment and tolerance assessment. As 

the proposed use on succulent lima beans does not include any regulated livestock feedstuffs or 

processed commodities, data requirements for livestock commodities and processed food and 

feed are not required. 

The results of the field trials are adequate. Following 4 or 5 broadcast foliar applications totaling 

5.84-7.42 lb ai/A (~1X the proposed maximum seasonal rate of 6.0 lb ai/A), residues of 

propamocarb were 0.21-0.65 ppm in/on 8 samples of succulent seeds harvested at 0 days after 

treatment (DAT). Following eight applications totaling 11.83 lb ai/A (NC trial), the highest 

residue was 1.01 ppm in/on succulent seeds. Overall, the highest-average field trial (HAFT) 

residue in succulent seeds was 0.99 ppm. No residue-decline data were submitted. 

Although eight field trials are typically required to support a use on lima beans, only five field 

trials [1 trial in North America Free Trade Agreement (NAFTA) Growing Zone 5 and 4 trials in 

Zone 2] are required to support a use on lima beans restricted to east of the Rocky Mountains. 

Therefore, the geographic representation of the four acceptable trials is adequate.

The residue data for lima beans were analyzed using the Organization for Economic Cooperation and Development (OECD) tolerance calculation procedures. The recommended 

tolerance is as follows:

Tolerances are established for residues of propamocarb, including its metabolites and degradates, 

in or on the commodities listed below resulting from the application of the hydrochloride salt of 

propamocarb. Compliance with the following tolerance levels is to be determined by measuring 

only propamocarb (propyl N-[3-(dimethylamino)propyl]carbamate).

Bean, lima, succulent 2.0 ppm

The available storage stability data adequately support the storage conditions and durations for 

samples from the lima bean field trials.
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Adequate confined and field rotational crop studies are available, and the data from these studies 

support the rotational crop restrictions currently specified on the proposed label.

5.3 Water Residue Profile

EFED provided EDWCs for surface water (using Tier II PRZM/EXAMS) and groundwater 

(using SCI-GROW) for propamocarb-HCl (see Table 5.3). The EDWCs were calculated based 

on the maximum application rate for current ornamental labels (2 x 64.3 lbs ai/A). The acute and 

chronic EDWCs in surface water are 8,762 ppb and 1,067 ppb, respectively. The groundwater 

EDWC is 15.6 ppb. 

Table 5.3 Summary of Estimated Surface Water and Groundwater Concentrations for Propamocarb-HCl.

1

Scenario Surface Water Conc. (ppb)2 Groundwater Conc. (ppb)

3

Acute 8,762 15.6 Chronic (non-cancer) 1,067

1. Memo, M. Ruhman, 11-DEC-2013, 368070.

2. From Tier II PRZM/EXAMS. Input parameters are based on the maximum application rate for ornamental labels (2 x 64.3 lbs ai/A).

3. From the SCI-GROW model. Input parameters are based on the maximum application rate for ornamental labels (2 x 64.3 lbs ai/A).

5.4 Dietary Risk Assessment

Acute and chronic aggregate dietary (food and drinking water) exposure and risk assessments 

were conducted using the DEEM-FCID (Ver. 3.16), which uses food consumption data from the 

USDA’s NHANES/WWEIA. This dietary survey was conducted from 2003 to 2008.

5.4.1 Description of Residue Data Used in Dietary Assessment

The acute and chronic dietary exposure assessments were unrefined, using tolerance-level 

residues and assuming 100% CT for all registered and proposed commodities. Exposure to 

drinking water was incorporated directly in the acute and chronic dietary assessments using the 

acute (peak) and chronic (annual average) concentrations for surface water generated by the 

PRZM-EXAMS model, respectively.

5.4.2 Percent Crop Treated Used in Dietary Assessment

The acute and chronic dietary exposure assessments assumed 100% CT for all registered and 

proposed uses.

5.4.3 Acute Dietary Risk Assessment

The results of the unrefined acute dietary assessment indicates that the acute dietary exposure 

estimates are below HED’s LOC (<100% aPAD) at the 95th exposure percentile for the general 

U.S. population and all other population subgroups. The acute dietary exposure is estimated at 

34% of the aPAD for females 13-49 years old, and 25% of the aPAD for the general U.S. 

population. The most highly exposed population subgroup is all infants (<1 year old) at 75% of 

the aPAD.

The acute assessments were highly conservative, using several upper-end assumptions. 

Additional refinements, such as inclusion of anticipated residues (ARs) and %CT data could be 

made in order to refine the future assessments. HED is confident that the assessment does not 

underestimate risk to the general U.S. population or any population subgroup.
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5.4.4 Chronic Dietary Risk Assessment

The results of the unrefined chronic dietary assessment indicate that the chronic dietary exposure 

estimates are below HED’s LOC (<100% cPAD) for the general U.S. population and all 

population subgroups. The chronic dietary exposure is estimated for the general U.S. population 

at 31% of the cPAD, and the most highly exposed population subgroup, all infants (<1 years 

old), at 50% of the cPAD.

The chronic assessment was highly conservative, using several upper-end assumptions. 

Additional refinements, such as inclusion of ARs and %CT data could be made in order to refine 

the future assessments. HED is confident that the assessment does not underestimate risk to the 

general U.S. population or any population subgroup.

5.4.5 Summary Table

Table 5.4.5. Summary of Dietary (Food and Drinking Water) Exposure and Risk for Propamocarb-HCl.

Population Subgroup

Acute Dietary

(95th Percentile) Chronic Dietary

Dietary Exposure 

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

General U.S. Population 0.507723 25 0.037228 31

All Infants (<1 year old) 1.496493 75* 0.060367 50*

Children 1-2 years old 0.762741 38 0.045611 38

Children 3-5 years old 0.633181 32 0.044067 37

Children 6-12 years old 0.473593 24 0.032129 27

Youth 13-19 years old 0.416725 21 0.028399 24

Adults 20-49 years old 0.501031 25 0.038290 32

Adults 50+ years old 0.449098 22 0.037513 31

Females 13-49 years old 0.510324 34 0.039067 33

*The subpopulation(s) with the highest risk estimates.

6.0 Residential (Non-Occupational) Exposure/Risk Characterization

There are no proposed residential uses at this time; however, there are registered residential uses 

for golf course turf (at a maximum application rate of 8.2 lb ai/A) that have been reassessed in 

this document to reflect updates to HED’s 2012 Residential SOPs

(http://www.epa.gov/pesticides/science/residential-exposure-sop.html) along with policy changes 

for body-weight assumptions. The revision of residential exposures will impact the humanhealth aggregate risk assessment for propamocarb-HCl.

6.1 Residential Handler Exposure

It is not anticipated that there will be residential handler exposure from the use on golf courses; 

therefore, an exposure assessment for residential handlers was not conducted.

6.2 Post-Application Exposure

Post-application dermal exposure was reassessed for adults and children based on the 2012 

Residential SOPs. Table 6.2 provides a summary of the residential post-application risk 

estimates from the registered use on golf course turf. There are no MOEs of concern (i.e., all 

MOEs ≥100).
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Table 6.2. Residential Post-application Non-cancer Exposure and Risk Estimates for Propamocarb-HCl.

Lifestage Post-application Exposure 

Scenario TTR (ug/cm2

)

1 Dose2 MOE3

Adult Golf course 

turf Dermal 1.50

0.397 380

Child (11 < 16 years old) 0.463 320

Child (6 < 11 years old) 0.543 280

1. TTR = chemical-specific data from MRID 45894314 for the PA site adjusted for differences in application rates. Study application rate = 8.1

lb ai/A, and label maximum application rate = 8.2 lb ai/A. See Appendix B for more information regarding the available data.

2. Dose = TTR * CF1 * TC * ET / BW. See Appendix A of D377624 for inputs.

3. MOE = Dermal NOAEL (150 mg/kg/day) / Dose (mg/kg/day).

6.3 Residential Risk Estimates for Use in Aggregate Assessment

Table 6.3 reflects the residential risk estimates that are recommended for use in the aggregate 

assessment for propamocarb-HCl:

 The recommended residential exposure for use in the adult and child aggregate 

assessment reflects dermal post-application exposure from golfing.

Table 6.3. Recommendations for the Residential Exposures for the Propamocarb Aggregate Assessment.1

Lifestage

Post-application Exposure (mg/kg/day)2 Residential Postapplication Total 

Exposure 

(mg/kg/day)

Residential PostDermal Inhalation Oral application MOE

Short-term

Adult Male 0.397 N/A N/A 0.397 380

Child (11 < 16 years old) 0.463 N/A N/A 0.463 320

Child (6 < 11 years old) 0.543 N/A N/A 0.543 280

1. Bolded risk estimates should contribute to the residential exposure portion of the aggregate assessment. 

2. Residential post-application exposure = exposure to treated turf while golfing in previously treated areas (see table 5.2.1).

6.4 Residential Bystander Post-application Inhalation Exposure

Based on the Agency's current practices, a quantitative post-application inhalation exposure 

assessment was not performed for propamocarb at this time primarily because of the low acute 

inhalation toxicity (Toxicity Category IV) and the vapor pressure (6.1 x 10-7 mm Hg at 25oC). 

However, volatilization of pesticides may be a source of post-application inhalation exposure to 

individuals nearby pesticide applications. The Agency sought expert advice and input on issues 

related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act

(FIFRA) Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report 

on March 2, 2010 (http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The 

Agency is in the process of evaluating the SAP report and may, as appropriate, develop policies 

and procedures to identify the need for and, subsequently, the way to incorporate postapplication inhalation exposure into the Agency's risk assessments. If new policies or 

procedures are developed, the Agency may revisit the need for a quantitative post-application 

inhalation exposure assessment for propamocarb.

6.5 Spray Drift

Spray drift is always a potential source of exposure to residents nearby to spraying operations. 

This is particularly the case with aerial application, but, to a lesser extent, could also be a 

potential source of exposure from the ground application method employed for propamocarb. 

The Agency has been working with the Spray Drift Task Force, EPA Regional Offices, and State 

Lead Agencies for pesticide regulation and other parties to develop the best spray-drift-
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management practices (see the Agency’s Spray Drift website for more information

(http://www.epa.gov/opp00001/factsheets/spraydrift.htm). On a chemical-by-chemical basis, the 

Agency is now requiring interim mitigation measures for aerial applications that must be placed 

on product labels/labeling. The Agency has completed its evaluation of the new database 

submitted by the Spray Drift Task Force, a membership of U.S. pesticide registrants, and is 

developing a policy on how to appropriately apply the data and the AgDRIFT®computer model 

to its risk assessments for pesticides applied by air, orchard airblast and ground hydraulic 

methods. After the policy is in place, the Agency may impose further refinements in spray-driftmanagement practices to reduce off-target drift with specific products with significant risk 

estimates associated with drift.

Although a quantitative residential post-application inhalation exposure assessment was not 

performed as a result of pesticide drift from neighboring treated agricultural fields, an inhalation 

exposure assessment was performed for flaggers. This exposure scenario is representative of a 

worse case inhalation (drift) exposure and may be considered protective of most outdoor 

agricultural and commercial post-application inhalation exposure scenarios. 

7.0 Aggregate Exposure/Risk Characterization

In accordance with the FQPA, HED must consider and aggregate pesticide exposures and risks 

from three major sources: food, drinking water, and residential exposures. In an aggregate 

assessment, exposures from relevant sources are added together and compared to quantitative 

estimates of hazard (e.g., a NOAEL or PAD), or the risks themselves can be aggregated. When 

aggregating exposures and risks from various sources, HED considers both the route and 

duration of exposure. In the case of propamocarb-HCl, aggregate risk assessments were 

performed for acute aggregate exposure (food + drinking water), short-term aggregate exposure 

(food + drinking water + residential), and chronic aggregate exposure (food + drinking water). 

An intermediate-term assessment was not conducted as intermediate-term residential exposures 

are not expected based on the current use patterns. However, as the short- and intermediate-term 

PODs are the same, the short-term aggregate is protective of any potential intermediate-term 

exposures. A cancer aggregate risk assessment was not performed because propamocarb-HCl is 

not carcinogenic. All potential exposure pathways were assessed in the aggregate risk 

assessment. 

7.1 Acute Aggregate Risk

The acute aggregate risk assessment takes into account exposure estimates from dietary

consumption of propamocarb-HCl (food + drinking water). The acute dietary exposure is 

estimated at 34% of the aPAD for females 13-49 years old, and 25% of the aPAD for the U.S. 

population (see Table 5.4.5). The most highly exposed population subgroup is all infants (<1 

year old) at 75% of the aPAD. Therefore, the acute aggregate risk associated with the proposed 

use of propamocarb-HCl does not exceed HED’s LOC for the general U.S. population or any

population subgroup.

7.2 Short-Term Aggregate Risk

The short-term aggregate risk assessment estimates risks likely to result from 1- to 30-day

exposures to propamocarb residues from food, drinking water, and residential pesticide uses. 

High-end estimates of residential exposure are used, and average values are used for food and 
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drinking water exposures.

Short-term aggregate risk assessments are necessary for both adults and children as there is 

potential for short-term post-application dermal exposure from the registered golf course use of 

propamocarb-HCl. For adult males, children (6 < 11 years old), and children (11 < 16 years old), 

the dermal post-application exposures estimates from contacting treated golf courses (see Table 

6.3) were aggregated with the chronic dietary exposures (food + drinking water; see Table 5.4.5) 

to provide a worst-case estimate of short-term aggregate risk for these population subgroups. 

For the short-term aggregate, the chronic dietary exposures were compared to the short-term 

incidental oral POD, which was based on decreased body weights observed in a two-generation 

reproduction study in both adults and offspring. Since the effects were observed in adults, the 

dietary exposures can be combined with the residential dermal exposures, which are also based 

on decreased body weights in adults. The 1/MOE approach was used since the toxicological 

effects for these exposures are similar (body-weight changes), and the LOCs are the same; 

however, different PODs were selected for the different routes of exposure. For the oral route, a

NOAEL of 65.41 mg/kg/day was selected from the two-generation reproduction study to be

protective of both parents and offspring. For the dermal route, a NOAEL of 150 mg/kg/day was 

selected from the dermal study. As the short-term aggregate MOEs are greater than 100, risks 

are not of concern.

Table 7.2. Short-Term Aggregate Risk Calculations.

Population LOC for 

Aggregate Risk1

Dietary (Food and Drinking 

Water) MOE2

Residential 

Dermal MOE3

Aggregate MOE (Dietary 

and Residential)4

Adult Male

100

1800 380 310

Adult Female 2300 320 280

Child 2000 280 240

1. The LOC (target MOE) includes 10X for interspecies extrapolation and 10X for intraspecies variation.

2. MOE dietary = [Short-term oral NOAEL (mg/kg/day)/Chronic dietary exposure (mg/kg/day)]. Short-term oral NOAEL = 65.41 mg/kg/day. See 

Table 5.4.4 for chronic dietary exposures.

3. MOE dermal = [Short-term dermal NOAEL (mg/kg/day)/high-end dermal residential exposure (mg/kg/day)]. Short-term derma NOAEL = 150 

mg/kg/day. See Table 6.4 for residential dermal exposures. 

4. MOE Aggregate = 1/[(1/MOE dietary) + (1/MOE dermal)].

7.3 Chronic Aggregate Risk

The chronic aggregate risk assessment takes into account average exposure estimates from 

dietary consumption of propamocarb (food + drinking water) and long-term residential uses. 

However, there are no registered or proposed uses that would result in long-term residential 

exposure; therefore, the chronic aggregate risk assessment takes into account exposure to food 

and drinking water only. The chronic dietary exposure is estimated at 31% of the cPAD for the 

U.S. population (see Table 5.4.5). The most highly exposed population subgroup is all infants 

(<1 year old) at 50% of the cPAD. Therefore, the chronic aggregate risk associated with the 

proposed use of propamocarb-HCl does not exceed HED’s LOC for the general U.S. population 

or any population subgroups.

8.0 Cumulative Exposure/Risk Characterization

Unlike other pesticides for which EPA has followed a cumulative risk approach based on a 

common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as 

to propamocarb-HCl and any other substances and propamocarb-HCl does not appear to produce 

a toxic metabolite produced by other substances. Although a carbamate, propamocarb is not an 
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N-methyl carbamate and does not cause cholinesterase inhibition. Thus it was not included in 

the N-methyl carbamate cumulative risk assessment. For the purposes of this tolerance action, 

therefore, EPA has not assumed that propamocarb-HCl has 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 the policy statements released by EPA’s Office of Pesticide Programs concerning common 

mechanism determinations and procedures for cumulating effects from substances found to have 

a common mechanism on EPA’s website at http://www.epa.gov/pesticides/cumulative/.

9.0 Occupational Exposure/Risk Characterization

Based on the proposed application scenarios and toxicological considerations, non-cancer 

occupational handler (dermal and inhalation) and post-application (dermal) assessments were 

conducted for the proposed uses on succulent lima beans. In addition, because of recent label 

revisions for the currently registered use on ornamentals, non-cancer occupational handler 

(dermal and inhalation) and post-application (dermal) assessments were reassessed for 

ornamentals. Occupational exposures were evaluated by HED and reviewed by the HED 

Science Advisory Council for Exposure (ExpoSAC; Memo, K. Lowe, 15-MAY-2013; 

D377624). 

9.1 Occupational Handler Exposure/Risk Estimates

HED uses the term handlers to describe those individuals who are involved in the pesticide 

application process. HED believes that there are distinct job functions or tasks related to 

applications and exposures can vary depending on the specifics of each task. Job requirements 

(amount of chemical used in each application), the kinds of equipment used, the target being 

treated, and the level of protection used by a handler can cause exposure levels to differ in a 

manner specific to each application event. 

Based on the anticipated use patterns and current labeling (see Tables 3.3.1 and 3.3.2), types of 

equipment and techniques that can potentially be used, occupational handler exposure is 

expected from the proposed use on lima beans, and the registered uses on ornamentals. The 

quantitative exposure/risk assessment developed for occupational handlers is based on the 

following scenarios: 

Proposed Use on Lima Beans:

 Mixing/loading Liquids for aerial, chemigation, and groundboom applications,

 Applying sprays via aerial and groundboom equipment, and,

 Flagging for aerial sprays applications.

Registered Use on Ornamentals:

 Mixing/loading liquids for groundboom applications,

 Applying sprays via groundboom equipment,

 Mixing/loading liquids for dip applications,

 Mixing/loading/applying liquids with a mechanically-pressurized handgun, and,

 Mixing/loading/applying liquids with a backpack sprayer.

For propamocarb-HCl, based on the proposed use on succulent lima beans, short- and 
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intermediate-term exposures are expected since the product can be applied up to 4X per season at 

the maximum single application rate, with a RTI of 7 days. In addition, the short- and 

intermediate-term PODs are the same for both dermal and inhalation routes; therefore, the shortterm exposure and risk estimates are protective of longer-term exposures.

Estimates of dermal and inhalation exposure were calculated for various levels of personalprotective equipment (PPE). Results are presented for “baseline,” defined as a single layer of 

clothing consisting of a long-sleeved shirt, long pants, shoes plus socks, no protective gloves, 

and no respirator, as well as baseline with various levels of PPE as necessary (e.g., gloves, 

respirator, etc.). The proposed propamocarb-HCl label for the use on lima beans directs

applicators and other handlers to wear long-sleeved shirt and long pants, chemical-resistant 

gloves made of any waterproof material such as polyethylene or polyvinyl chloride, and shoes 

plus socks. The registered labels with ornamental uses direct applicators and other handlers to 

wear long-sleeved shirt and long pants, chemical-resistant gloves made of any waterproof 

material, shoes plus socks, and a chemical-resistant apron when making dip applications.

It is the policy of HED to use the best available data to assess handler exposure. Sources of 

generic handler data, used as surrogate data in the absence of chemical-specific data, include 

PHED 1.1, the AHETF database, the ORETF database, or other registrant-submitted 

occupational exposure studies. Some of these data are proprietary (e.g., AHETF data), and 

subject to the data protection provisions of FIFRA. The standard values recommended for use in 

predicting handler exposure that are used in this assessment, known as “unit exposures,” are 

outlined in the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table”

(http://www.epa.gov/opp00001/science/handler-exposure-table.pdf), which, along with 

additional information on HED policy on use of surrogate data, including descriptions of the 

various sources, can be found at the Agency website

(http://www.epa.gov/pesticides/science/handler-exposure-data.html). 

HED has no data to assess exposures to pilots using open cockpits. The only data available are

for exposure to pilots in enclosed cockpits. Therefore, risks to pilots are assessed using the 

engineering control (enclosed cockpits) and baseline attire (long-sleeve shirt, long pants, shoes, 

and socks); pilots are not required to wear protective gloves. With this level of protection, there 

are no risk estimates of concern for applicators.

The Agency matches quantitative occupational exposure assessment with appropriate 

characterization of exposure potential. While HED presents quantitative risk estimates for 

human flaggers where appropriate, agricultural aviation has changed dramatically over the past 

two decades. According the 2012 National Agricultural Aviation Association (NAAA) survey of 

their membership, the use of the Global Positioning System (GPS) for swath guidance in 

agricultural aviation has grown steadily from the mid 1990s. Over the same time period, the use 

of human flaggers for aerial pesticide applications has decreased steadily from ~15% in the late 

1990s to only 1% in the most recent (2012) NAAA survey. The Agency will continue to monitor 

all available information sources to best assess and characterize the exposure potential for human 

flaggers in agricultural aerial applications.

The occupational handler exposure and risk estimates indicate that short- and intermediate-term 

dermal and inhalation combined MOEs are not of concern to HED (i.e., MOEs > 100) with 

baseline attire or with the addition of gloves (as required on the labels). For the proposed use on 

lima beans, the dermal plus inhalation MOEs range from 100 to 4,500 with baseline attire (see 

Table 9.1.1). For the registered use on ornamentals, the dermal plus inhalation MOEs range 
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from 120 to 39,000 with baseline attire and/or gloves (see Table 9.1.2).
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Table 9.1.1. Short-/Intermediate-Term Occupational Exposure and Risk Estimates for Proposed Use of Propamocarb on Lima Beans.

Exposure 

Scenario Crop / Target Category Application Rate1

Amount 

Handled / 

Area 

Treated2

Dermal 

Unit 

Exposures

(ug/lb ai)3

Inhalation 

Unit 

Exposures

(ug/lb ai)3

Dermal 

Dose 

(mg/kg/day)4

Dermal 

MOE5

Inhalation Dose 

(mg/kg-day)6

Inhalation 

MOE7

Combined 

MOE8

Mixing/Loading Liquids

Aerial 

application

Lima beans 1.5 lb ai/A

350 acres

220 0.219

1.45 100 0.00144 45,000 100

Chemigation 

applications 1.45 100 0.00144 45,000 100

Groundboom 

applications 80 acres 0.33 450 0.000329 200,000 450

Applying Sprays

Aerial 

applications Lima beans 1.5 lb ai/A

350 acres 5 (EC) 0.068 (EC) 0.0329 (EC) 4,600 (EC) 0.000446 (EC) 150,000 (EC) 4,500 (EC)

Groundboom 

applications 80 acres 78.6 0.34 0.118 1,300 0.00051 130,000 1,300

Flagging

Aerial 

applications Lima beans 1.5 lb ai/A 350 acres 11 0.35 0.0723 2,100 0.0023 28,000 2,000

1. Based on proposed label (Reg. #264-678).

2. ExpoSAC Policy #9.1.

3. Based on “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (September 2012); includes data from PHED/ORETF/AHETF. Level of mitigation: Baseline (single layer of clothing, no gloves, 

no respirator) for all scenarios except for aerial applicators which is assessed using engineering controls (EC).

4. Dermal Dose = Dermal Unit Exposure (ug/lb ai) x Conversion Factor (0.001 mg/ug) x Application Rate (lb ai/acre or gal) x Area Treated or Amount Handled (A or gal/day) / BW (80 kg).

5. Dermal MOE = Dermal NOAEL (150 mg/kg/day)/Dermal Dose (mg/kg/day).

6. Inhalation Dose = Inhalation Unit Exposure (ug/lb ai) x Conversion Factor (0.001 mg/ug) x Application Rate (lb ai/acre or gal) x Area Treated or Amount Handled (A or gal/day) / BW (80 kg).

7. Inhalation MOE = Inhalation NOAEL (65.41 mg/kg/day)/ Inhalation Dose (mg/kg/day).

8. Total MOE = 1/(1/Dermal MOE + 1/Inhalation MOE)
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Table 9.1.2. Short-/Intermediate-Term Occupational Exposure and Risk Estimates for Reassessment of Ornamental Use of Propamocarb.

Exposure 

Scenario

Crop / Target 

Category

Application 

Rate1

Amount 

Handled / 

Area 

Treated2

Dermal Unit 

Exposures

(ug/lb ai)3

Inhalation 

Unit 

Exposures

(ug/lb ai)3

Dermal Dose 

(mg/kg/day)4

Dermal 

MOE5

Inhalation 

Dose 

(mg/kgday)6

Inhalation 

MOE7

Combined 

MOE8

Mixing/Loading Liquids

Groundboom 

applications

Greenhouse/Nursery 

ornamentals

46 lb ai/A 60 acres 220 

(baseline)

37.6 

(with gloves)

0.219

7.59 

(baseline)

1.3 

(with gloves)

20 

(baseline)

120 

(with gloves)

0.00755 8,700

20

(baseline)

120 

(with gloves)

Dip 

applications

0.014 lb 

ai/gallon

100 gallons 0.00385 

(baseline)

39,000

(baseline) 0.00000384 17,000,000 39,000

1000 gallons 0.0385 

(baseline)

3,900

(baseline) 0.0000384 1,700,000 3,900

Applying Sprays

Groundboom 

applications

Greenhouse/Nursery 

ornamentals 46 lb ai/A 60 acres

78.6

(baseline)

16.1

(with gloves)

0.34

2.71

(baseline)

0.555

(with gloves)

55

(baseline)

270

(with gloves)

0.0117 5,600

54

(baseline)

260

(with gloves)

Mixing/Loading/Applying Liquids

Backpack 

sprayer

Nursery 

(ornamentals, 

container stock)

0.014 lb 

ai/gallon

40 gallons 8,260 2.58 0.0579 2,600 0.000018 3,600,000 2,600

Mechanicallypressurized 

handgun

Greenhouse 

(ornamentals, roses, 

cut flowers, 

container stock) 1000 gallons

3,500 120 0.613 240 0.021 3,100 220

Nursery 

(ornamentals, 

container stock)

1,300 3.9 0.228 660 0.000683 96,000 660

1. Based on registered labels (Reg. #432-942, #55260-9, and #83070-8).

2. ExpoSAC Policy #9.1.

3. Based on “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (September 2012); includes data from PHED/ORETF/AHETF. Level of mitigation: Baseline (single layer of clothing, no gloves, 

no respirator), Baseline with gloves, or engineering controls (EC; closed cockpit) for aerial applicators. 

4. Dermal Dose = Dermal Unit Exposure (ug/lb ai) x Conversion Factor (0.001 mg/ug) x Application Rate (lb ai/acre or gal) x Area Treated or Amount Handled (A or gal/day) / BW (80 kg).

5. Dermal MOE = Dermal NOAEL (150 mg/kg/day)/Dermal Dose (mg/kg/day).

6. Inhalation Dose = Inhalation Unit Exposure (ug/lb ai) x Conversion Factor (0.001 mg/ug) x Application Rate (lb ai/acre or gal) x Area Treated or Amount Handled (A or gal/day) / BW (80 kg).

7. Inhalation MOE = Inhalation NOAEL (65.41 mg/kg/day)/ Inhalation Dose (mg/kg/day).

8. Total MOE = 1/(1/Dermal MOE + 1/Inhalation MOE).
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9.2 Occupational Post-application Exposure/Risk Estimates

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

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

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

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

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

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

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

For the proposed use on lima beans, post-application exposure is anticipated based on the use 

pattern. For the registered ornamental use, post-application exposure is not anticipated since the 

labels indicate applications are to be limited to soil-directed sprays.

9.2.1 Occupational Post-application Dermal Exposure/Risk Estimates

HED classifies exposures from 1 to 30 days as short-term and exposures 30 days to six months 

as intermediate-term. For propamocarb, based on the proposed use, short- and intermediate-term 

exposures are expected since the product can be applied up to 4X per season at the maximum 

single application rate, with a RTI of 7 days. In addition, the short- and intermediate-term PODs

are the same for both dermal and inhalation routes; therefore, the short-term exposure and risk 

estimates are protective of longer-term exposures.

It is the policy of HED to use the best available data to assess post-application exposure. 

Sources of generic post-application data, used as surrogate data in the absence of chemicalspecific data, are derived from ARTF exposure monitoring studies, and, as proprietary data, are 

subject to the data protection provisions of FIFRA. The standard values recommended for use in 

predicting post-application exposure that are used in this assessment, known as “transfer 

coefficients”, are presented in the ExpoSAC Policy 3

(http://www.epa.gov/pesticides/science/exposac_policy3.pdf)” which, along with additional 

information about the ARTF data, can be found at the Agency website

(http://www.epa.gov/pesticides/science/post-app-exposure-data.html). 

The short- and intermediate-term post-application exposure scenarios associated with the

proposed uses for propamocarb are summarized in Table 9.2.1. All scenarios resulted in MOEs 

greater than the LOC of 100 (ranging from 190 to 5,100) on day 0 (12 hours after application) 

and, therefore, are not of concern to HED.

Table 9.2.1. Summary of Short- and Intermediate-term Post-application Risk Estimates for Propamocarb.

Crop/Site Activities Transfer Coefficient 

(cm2/hr) DFR/TTR1 Dermal Dose (mg/kg/day)2 MOE3

Lima beans

Hand weeding 70

4.21

0.0295 5,100

Scouting 210 0.0884 1,700

Scouting, Hand harvesting 1000 0.463 320

Irrigation (hand set) 1900 0.8 190

1. DFR = Application Rate x F x (1-D)tx 4.54E8 μg/lb x 2.47E-8 acre/cm2; where F = 0.25 and D = 0.10 per day. 

2. Daily Dermal Dose = [DFR (μg/cm2) × Transfer Coefficient × 0.001 mg/μg × 8 hrs/day  BW (80 kg).

3. MOE = POD (150 mg/kg/day) / Daily Dermal Dose. 
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9.2.2 Occupational Post-application Inhalation Exposure/Risk Estimates

Based on the Agency's current practices, a quantitative post-application inhalation exposure 

assessment was not performed for propamocarb at this time primarily because of the low acute 

inhalation toxicity (Toxicity Category IV) and the vapor pressure (6.1 x 10-7 mm Hg at 25oC). 

However, there are multiple potential sources of post-application inhalation exposure to 

individuals performing post-application activities in previously treated fields. These potential 

sources include volatilization of pesticides and resuspension of dusts and/or particulates that 

contain pesticides. The Agency sought expert advice and input on issues related to volatilization 

of pesticides from its FIFRA SAP in December 2009, and received the SAP’s final report on 

March 2, 2010 (http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The 

Agency is in the process of evaluating the SAP report as well as available post-application 

inhalation exposure data generated by the ARTF and may, as appropriate, develop policies and 

procedures, to identify the need for and, subsequently, the way to incorporate occupational postapplication inhalation exposure into the Agency's risk assessments. If new policies or 

procedures are put into place, the Agency may revisit the need for a quantitative occupational 

post-application inhalation exposure assessment for propamocarb.

Although a quantitative occupational post-application inhalation exposure assessment was not 

performed, an inhalation exposure assessment was performed for occupational/commercial 

handlers. Handler exposure resulting from application of pesticides outdoors is likely to result in 

higher exposure than post-application exposure. Therefore, it is expected that these handler 

inhalation exposure estimates would be protective of most occupational post-application 

inhalation exposure scenarios.

For the greenhouse ornamental uses, it should be noted that the WPS for Agricultural Pesticides 

contains requirements for protecting workers from inhalation exposures during and after 

greenhouse applications through the use of ventilation requirements [40 CFR 170.110, (3) 

(Restrictions associated with pesticide applications)].

10.0 References

K. Lowe, 15-MAY-2013, D377624, Propamocarb. REVISED Occupational and Residential 

Exposure Assessment for a Proposed Use on Lima Beans and an Assessment for a Registered 

Use on Ornamentals.

O. Odiott, 15-JULY-1995, The HED Chapter of the Reregistration Eligibility Decision 

Document (RED) for Propamocarb.

G. Reddy et al., 12-OCT-2005, TXR #0052538, DER Subchronic Neurotoxicity Study in Rats.

J. Rowell, 03-MAY-2000, D264293, Propamocarb HCl. Results of the Health Effects Division 

(HED) Metabolism Assessment Review Committee (MARC) Meeting of 4/6/00.

J. Rowell, 15-MAY-2000, D266084, Propamocarb Hydrochloride in/on Potatoes and Livestock 

Commodities. Review of Amendment Submitted in Response to HED’s Memo of 10/17/96.

J. Rowell, 3-OCT-2000, D268955, Propamocarb Hydrochloride in or on Potatoes and Tomatoes. 

Results of Petition Method Validation (PMV) Request. 
Propamocarb-HCl Human-Health Risk Assessment DP# 367968

Page 31 of 38

M. Ruhman, 11-DEC-2012, D368070, Propamocarb hydrochloride (Propamocarb-HCl): 

Refined Drinking Water Estimated Environmental Concentrations for use in the Human Health 

Risk Assessment in support of the proposed new use on Lima beans.

J. Tyler, et al., 20-FEB-2004, D284504, Propamocarb Hydrochloride in/on Fruiting Vegetables, 

Cucurbit Vegetables, and Head and Leaf Lettuce. Health Effects Division (HED) Risk 

Assessment.

J. Tyler, 10-MAR-2005, D304509, Propamocarb Hydrochloride on Potatoes. HED 

Determination of Appropriate Livestock Tolerances.

J. Tyler, 15-MAY-2013, D359104, Propamocarb Hydrochloride (Propamocarb-HCl): Petition 

for Tolerances and Use on Lima Beans (Succulent). Summary of Analytical Chemistry and 

Residue Data.

J. Tyler, 15-MAY-2013, D367969, Propamocarb Hydrochloride (Propamocarb-HCl) Acute and 

Chronic Aggregate Dietary (Food and Drinking Water) Exposure and Risk Assessments for the 

Section 3 Registration Action on Lima Beans (Succulent). 

J. Van Alstine, 14-FEB-2013, TXR#0056466, Propamocarb Hydrochloride: Summary of Hazard 

and Science Policy Council (HASPOC) Meeting of September 13, 2012: Recommendations on 

the Requirement of a Subchronic Inhalation Study for Propamocarb Hydrochloride. 

cc: J. Tyler, G. Kramer, A. Dunbar, K. Lowe

RDI: RAB1 (2/20/13); G. Kramer (2/27/13)

J. Tyler: S-10943: Potomac Yard 1 (PY1): (703) 305-5564: 7509P: RAB1
Propamocarb-HCl Human-Health Risk Assessment DP# 367968

Page 32 of 38

Appendix A. Toxicology Profile Tables.

Table A.2.1. Acute Toxicity Profile – Propamocarb-HCl.

Guideline 

No. Study Type MRID(s) Results Toxicity Category

870.1100 Acute oral [rat] 41278115 LD50 = 2900 mg/kg (M)

LD50 = 2000 mg/kg (F) III

870.1200 Acute dermal [rat] 41278116 LD50 >3,000 mg/kg III

870.1300 Acute inhalation [rat] 93193044 LC50 >7.90 mg/L (Limit Test) IV

870.2400 Acute eye irritation 41278117 Slight irritation, resolved within 72 hrs III

870.2500 Acute dermal irritation 

[rabbit]

41278118 No erythema after 24 hours IV

870.2600 Skin sensitization 

[guinea pig]

00083808 Non-sensitizer

-

Table A.2.2. Subchronic, Chronic, and Other Toxicity Profile.

Guideline 

No. Study Type MRID No. (year)/ Classification /Doses Results

870.3100 90-Day oral toxicity 

(mouse)

44810401 (1998)

Acceptable/guideline

0, 5000, 10,000, or 20,000 

ppm

M: 0, 318, 646, or 1363 

mg/kg/day 

F: 0, 363, 716, or 1549 

mg/kg/day

NOAEL = 363 mg/kg/day in females and 646 

mg/kg/day in males.

LOAEL = 716 mg/kg/day in females, based on 

decreased body weight and body-weight gain and 

decreased food efficiency. LOAEL in males is 1363 

mg/kg/day based on decreased food efficiency.

870.3100 90-Day oral toxicity 

(rat)

46145201 (2001)

Acceptable/guideline

0, 375, 1500, or 6000 ppm

0/0, 28/34, 104/130, and 

434/540 mg/kg/day [M/F]

NOAEL = 1500 ppm (104/130 mg/kg/day [M/F]).

LOAEL = 6000 ppm (equivalent to 434/540 

mg/kg/day [M/F]) based on decreased body-weight 

gains in females throughout the study, and 

histopathological effects in the brain (moderate to 

severe vacuolation of the choroid plexus) and the 

lacrimal glands (minimal to slight vacuolar 

alteration).

870.3150 90-Day oral toxicity 

in dogs

46145202 (2001) 

Acceptable/guideline

0, 1000, 3000, or 10,000 ppm

0/0, 45/51, 131/161, and 

433/471 mg/kg/day [M/F] 

NOAEL = 3000 ppm (131/161 mg/kg/day [M/F]).

LOAEL = 10,000 ppm (equivalent to 433/471 

mg/kg/day [M/F]) based on vacuolation alterations 

of the trachea, lungs, salivary glands, stomach, 

lymph nodes, and lacrimal glands; and retinal 

degeneration and hyporeflectivity of the fundus.

870.3200 21-Day dermal 

toxicity (rabbits)

00071526 (1980)

Acceptable/guideline

M & F: 0, 150, 525, or 1500 

mg/kg/day

NOAEL = 150 mg/kg/day for both sexes.

LOAEL = 525 mg/kg/day based on dose-related skin 

irritation and depressed body-weight gain.

870.3200 28-Day dermal 

toxicity (rats)

45894201 (2002)

Acceptable/guideline

M & F: 0, 75, 300, or 1200 

mg/kg bw/day

Systemic NOAEL >1200 mg/kg/day.

Systemic LOAEL was not established.

Dermal NOAEL = 300 mg/kg/day.

Dermal LOAEL = 1200 mg/kg/day based on dermal 

effects (scabs, erythema maculate, focal erythema, 

necrosis, and ulcerative inflammation) in the treated 

skin of the females.

870.3700a Prenatal 

developmental in 

(rat)

00101641 (1981) and 

93193042 (1990)

Acceptable/guideline

F: 0, 74, 221, 740, or 2210 

mg/kg/day

Maternal NOAEL = 221 mg/kg/day.

LOAEL = 740 mg/kg/day based on mortality.

Developmental NOAEL = 221 mg/kg/day.

LOAEL = 740 mg/kg/day based on GD 20 fetal 

death and a possible increase in minor skeletal 

anomalies.
Propamocarb-HCl Human-Health Risk Assessment DP# 367968

Page 33 of 38

Table A.2.2. Subchronic, Chronic, and Other Toxicity Profile.

Guideline 

No. Study Type MRID No. (year)/ Classification /Doses Results

870.3700a Prenatal 

developmental in 

(rat)

46145203 (2001), 46462801 

(2005)

Acceptable/guideline

F: 0, 31, 123, and 456 

mg/kg/day

Maternal NOAEL = 123 mg/kg/day.

Maternal LOAEL = 456 mg/kg/day based on 

decreased body weights, body-weight gains, and 

food consumption.

Developmental NOAEL = 123 mg/kg/day.

Developmental LOAEL = 456 mg/kg/day based on 

decreased fetal body weights, and increased 

incidences of small fetus, inter-atrial septal defect, 

and hemorrhage in the ears, upper GI tract, and 

nasopharynx/sinuses and post-implantation loss.

870.3700b Prenatal 

developmental in 

(rabbit)

00072574 (1981), 93193043 

(date not available) 

Acceptable/guideline

F: 0, 15, 45, 150, 300, and 

600 mg/kg/day

Maternal NOAEL = 150 mg ai/kg/day

LOAEL = 300 mg /kg/day based on decreased bodyweight gains for GD 6-18 and possible increased 

abortions.

Developmental NOAEL = 150 mg/kg/day

LOAEL = 300 mg/kg/day based on increased postimplantation loss.

870.3700b Prenatal 

developmental in 

(rabbit)

46145204 (2002, 2005) 

Acceptable/guideline

F: 0, 20, 76, and 269 

mg/kg/day 

Maternal NOAEL = 76 mg/kg/day.

Maternal LOAEL = 269 mg/kg/day based on 

decreased body-weight gains, and food consumption.

Developmental NOAEL = 269 mg/kg/day.

Developmental LOAEL was not observed.

870.3800 Reproduction and 

fertility effects

(rat)

44730103 (1998), 44730102 

(1998)

Acceptable/guideline

F0 M: 9.95, 65.41, or 406.69 

mg/kg/day

F0 F: 12.79, 76.78, or 467.13 

mg/kg/day

F1 M: 12.08, 75.36, or 

484.90 mg/kg/day 

F1 F: 14.22, 85.32, or 541.78 

mg/kg/day

Parental/Systemic NOAEL = 65.41 mg/kg/day for 

males and 76.78 mg/kg/day for females.

LOAEL = 406.69 mg/kg/day for males and 467.13 

mg/kg/day for females based on decreased body 

weights.

Reproductive/Offspring NOAEL = 65.41 mg/kg/day 

for males and 76.78 mg/kg/day for females.

LOAEL = 406.69 mg/kg/day for males and 467.13 

mg/kg/day for females based on reduced pup 

weights.

870.3800 Reproduction and 

fertility effects

(rat)

46145205 (2002)

Acceptable/guideline

0, 50, 200, or 1000 mg/kg 

bw/day

Parental/Systemic NOAEL = 200 mg/kg/day. 

Parental/Systemic LOAEL = 1000 mg/kg bw/day 

(limit dose), based on clinical signs of toxicity (preand post-dose salivation, reddish material around the 

mouth, and urine staining) and decreased bodyweight gains in the females during gestation and 

lactation and vacuolar changes in choroid plexus of 

brain in males and females. 

Offspring NOAEL = 200 mg/kg/day.

Offspring LOAEL = 1000 mg/kg/day based upon 

increased pup deaths, decreased viability and 

lactation indices and litter size, and decreased pup 

body weights and body-weight gains.

Reproductive NOAEL = 200 mg/kg/day.

Reproductive LOAEL = 1000 mg/kg/day based upon

increased vacuolization and decreased weight of the 

epididymides and decreased sperm count, motility, 

and normal morphology in both generations.

870.4100 Chronic toxicity

(mouse)

00101638 (1981)

Acceptable/guideline

M: 0, 1.0, 5.1, or 25.6 

mg/kg/day

F: 0, 1.3, 6.5, or 31.9 

mg/kg/day

NOAEL = 25.6 mg/kg/day.

LOAEL = >25.6 mg/kg/day. There were no signs of 

toxicity attributable to treatment at any dose level.
Propamocarb-HCl Human-Health Risk Assessment DP# 367968

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Table A.2.2. Subchronic, Chronic, and Other Toxicity Profile.

Guideline 

No. Study Type MRID No. (year)/ Classification /Doses Results

870.4100 Chronic toxicity 

(dog)

41278119 (1977) and 

43044201 (1985)

Acceptable/guideline

M: 0, 22.75, 70.81, or 

243.32 mg ai/kg/day 

F: 0, 22.752, 72.91, or 

228.31 mg/kg/day

NOAEL was not achieved.

LOAEL = 22.75 mg/kg/day based upon body-weight 

gain depression, decreased food efficiency and focal 

or multi-focal chronic erosivegastritis.

870.4100 Chronic toxicity 

(dog)

46145207 (2003) 

Acceptable/guideline

0/0, 39/42, 97/116, and 

378/404 mg/kg/day [M/F]

NOAEL = 39/42 mg/kg/day.

LOAEL = 97/116 mg/kg/day based upon retinal 

degeneration and hyporeflectability in males; 

vacuolar alterations of the duodenum, lungs, pyloric 

glands of the stomach, and trachea in both sexes, rat

testes and testicular blood vessels in males and 

vagina in females.

870.4200 Carcinogenicity

(mouse)

44693801 (1998)

Acceptable/guideline

M: 0, 11, 84, or 690 

mg/kg/day

F: 0, 12, 95, or 883 

mg/kg/day

NOAEL = 12 mg/kg/day in females and  690.0 mg 

/kg/day in males.

LOAEL = 95 mg/kg/day in females based on 

decreased body weight and body-weight gains.

No evidence of carcinogenicity.

870.4200 Carcinogenicity

(mouse)

46145208 (2003)

Acceptable/guideline

0/0, 15/19, 106/136, and 

790/1014 mg/kg/day [M/F

NOAEL = 106/136 mg/kg/day

LOAEL = 790/1014 mg/kg/day based upon 

decreased body weight and body-weight gains in 

both sexes and emaciation in females.

No Evidence of carcinogenicity.

870.4200 Carcinogenicity

(rat)

44730101 (1998)

Acceptable/guideline 

M: 0, 10.4, 84, or 682 

mg/kg/day

F: 0, 14.0, 112, or 871 

mg/kg/day

NOAEL = 84 mg/kg/day in males, 112 mg/kg/day in 

females.

LOAEL = 682 mg/kg/day in males, 871 mg/kg/day 

in females based on decreased body weight and 

body-weight gain, decreased food consumption, and 

an increased incidence of vacuolization of choroid 

plexus ependymal cells in the brain in both sexes and 

decreased water consumption in the females.

No evidence of carcinogenicity.

870.4300 Chronic/ 

Carcinogenicity

(rat)

46145209 (2001)

Acceptable/guideline 

0/0, 150/155, 368/392, and 

989/1022 mg/kg/day in M/F

NOAEL = 150/155 mg/kg bw/day.

LOAEL = 368/392 mg/kg bw/day based on clinical 

signs in females, and decreased body weights, bodyweight gains, and food consumption in both sexes 

and macroscopic and microscopic lesions in the 

reproductive system in males eye opacity in females.

No evidence of carcinogenicity.

870.5100 reverse gene 

mutation assay in 

bacteria

41278121 (1987)

Acceptable/guideline

There was no evidence of induced mutant colonies 

over background.

870.5100 reverse gene 

mutation assay in 

bacteria

45894202 (2001)

Acceptable/non-guideline

There was no evidence of induced reverse mutation 

[increased revertant colonies over background in 4 

replicate trials of one bacterial strain (E. Coli WP2 

uvrA)].

870.5375 in vitro mammalian 

cytogenetics assay

41278122 (1987)

Acceptable/guideline

Increases in aberrant metaphases were within the 

historical control range.

870.5375 in vitro mammalian 

cytogenetics assay

45894203 (2001)

Acceptable/guideline

There was no evidence of chromosome aberrations 

induced over background in the presence or absence 

of S9-activation.

870.5395 bone marrow 

micronucleus assay

00101642 (1980)

Acceptable/guideline with 

00101643

There was no significant increase in the frequency of 

micronucleated polychromatic erythrocytes in bone 

marrow at any dose tested.

870.5395 bone marrow 

micronucleus assay

00101643 (1980)

Acceptable/guideline with 

00101642

There was no significant increase in the frequency of 

micronucleated polychromatic erythrocytes in bone 

marrow after any treatment time.
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Page 35 of 38

Table A.2.2. Subchronic, Chronic, and Other Toxicity Profile.

Guideline 

No. Study Type MRID No. (year)/ Classification /Doses Results

870.5575 Saccharomyces 

cerevisiae, mitotic 

recombination, gene 

conversion assay

00101624 (1977)

Acceptable/guideline with 

00101645

Under the conditions of the study there was no 

evidence of gene conversion. 

870.5575 Saccharomyces 

cerevisiae, mitotic 

recombination, gene 

conversion assay

00101645 (1980)

Acceptable/guideline with 

41278124

There was no evidence of gene conversion in the 

tested strains without activation.

870.5575 Saccharomyces

cerevisiae, mitotic 

recombination, gene 

conversion assay

41278124 (1985)

Acceptable/guideline with 

00101645

There was no evidence of gene conversion in the 

tested strains with activation.

870.6200a Acute neurotoxicity 

screening battery 

(rat)

43062301 (1993) and 

43013101 (1993)

Acceptable/guideline

M & F: 0, 20, 200, or 2000 

mg/kg/day

NOAEL = 200 mg/kg/day.

LOAEL =2000 mg/kg/day based on soiled fur coat 

(both sexes) and decreased motor activity 8 hours 

post-dosing (females only).

870.6200a Acute neurotoxicity 

screening battery 

(rat)

45894205 (2002) and 

46598501 (2005) 

Acceptable/guideline

0, 20, 200, or 2000 mg/kg

NOAEL = 200 mg/kg/day.

LOAEL =2000 mg/kg/day based on decreased motor 

activity (overall session distance moved, number of 

movements, and mean velocity) on Day 0 in males 

and females.

870.6200b Subchronic 

neurotoxicity 

screening battery 

(rat)

43013102 (1993)

Acceptable/guideline

M: 0, 12.9, 134.6, or 1320.8 

mg/kg/day

F: 0, 14.2, 148.5, or 1485.6 

mg/kg/day

NOAEL = 1320.8 mg/kg/day in males and 1485.6 

mg/kg/day in females.

LOAEL = not observed.

870.6200b Subchronic 

neurotoxicity 

screening battery 

(rat)

45894206 (2002, 2005)

Acceptable/guideline

0, 22.5/24.9, 89.7/99.5, and 

352.8/382.8 mg/kg/day 

[M/F]

NOAEL = 89.7/99.5 mg/kg/day [M/F].

LOAEL = 352.8/382.8 mg/kg/day [M/F] based on 

decreased body-weight gain, and food consumption 

in females and intra-epithelial vacuolization of the 

choroid plexus in the cerebrum and cerebellum in 

both sexes.

870.7485 Metabolism and 

pharmacokinetics

(rat)

00101640 (1978)

Unacceptable/guideline

M & F: 0.5 mg/kg

A higher dose (at least equivalent to levels of human 

exposure) should have been tested, and the 

metabolites should have been identified.
Propamocarb-HCl Human-Health Risk Assessment DP# 367968

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Table A.2.2. Subchronic, Chronic, and Other Toxicity Profile.

Guideline 

No. Study Type MRID No. (year)/ Classification /Doses Results

870.7485 Metabolism and 

pharmacokinetics

(rat)

45894207 (2000)

acceptable/guideline

M & F: 1 & 100 mg/kg

Overall recovery of the radioactive dose from both 

sexes was 92-97%. The majority of the dose was 

recovered in the urine and cage wash within 6 hours 

in the 1 or 100 mg/kg single dose groups (56-69% 

dose) and within 24 hours in the 1 mg/kg repeated 

group (87-88% dose). Over the entire study, 87-93% 

dose was detected in the urine, and minimal 

radioactivity was detected in the feces (3-6% dose), 

carcass (0.4-1% dose), and cage debris (<0.3% dose) 

in all groups. Pharmacokinetics parameters for both 

blood and plasma were Cmax = 0.20-0.25 μg equiv./g, 

Tmax = 0.50-0.88 h, and T1⁄2 = 1.7-2.9 h in all animals. 

This information indicates that propamocarb is 

quickly and extensively absorbed, and rapidly 

excreted. Sex related differences were not observed, 

and increasing the dose or number of treatments did 

not change the excretion profile. The distribution 

and concentration of radioactivity in tissues were 

generally similar over time for both sexes from both 

the single and repeated 1 mg/kg dose groups. 

Excluding the GI tract, concentrations of 

radioactivity at 0.75 hours post-dose were highest in 

kidneys, liver, and adrenals (repeated dose males 

only) at 1.28-4.39 μg equiv./g. Initial concentrations 

in heart, lung, spleen, ovaries and adrenals (0.308-

0.594 μg equiv./g) were also slightly higher than in 

whole blood and plasma (0.227-0.336 μg equiv./g), 

but radioactivity in the remaining tissues were at or 

below the concentrations in blood. Radioactivity in 

tissues declined steadily over time, and by 24 hours 

post-dose, the maximum concentrations of 

radioactivity were generally associated with the liver 

and the GI tract (0.056-0.094 μg equiv./g). 

Concentrations of radioactivity were higher in 

tissues from the 100 mg/kg group, but the increase 

was not proportional to dose. The general 

distribution of radioactivity in this group was similar 

to the two 1 mg/kg dose groups. In each dose group, 

the predominant metabolites were carbonyl 

propamocarb at 24-27% dose in the 1 mg/kg groups 

and 13-15% dose in the 100 mg/kg group, and 3-

hydroxypropyl propamocarb at 8-12% dose in the 1 

mg/kg groups and 19-24% dose in 100 mg/kg 

animals.

Special 

studies

00130267 (1981)

Unacceptable/nonguideline

In vitro: Rat and dog 

plasma incubated 

for 30 min at 37C

Dose: 0.925 to 74 

mg a.i./ml plasma 

In vivo: Dog

Dose: Single oral 

Previcur N (67.5%) 

= 674 mg a.i./kg 

b.w.

1 male & 1 female died 

within 43 min; exhibited 

tremors, convulsions, 

respiratory, standstill, and 

death. ChE inhibition dead 

animals, plasma - no effect; 

RBC - 19-54%, and brain 

decrease 10X the controls. 

No appreciable decrease in 

ChE in the surviving dog.

Conclusion: The 

cholinesterase inhibition 

studies were of questionable 

quality. The chemical does 

not cause any appreciable 

inhibition of cholinesterase.

Special studies
Propamocarb-HCl Human-Health Risk Assessment DP# 367968

Page 37 of 38

Table A.2.2. Subchronic, Chronic, and Other Toxicity Profile.

Guideline 

No. Study Type MRID No. (year)/ Classification /Doses Results

870.7600 Immunotoxicity

(rat)

48752605 (2011)

Acceptable/guideline

0, 1400, 4500, or 15000 ppm

(0, 65.3, 205.6 and 807.7 

mg/kg/day [F])

Systemic NOAEL = 4500 ppm (205.6 mg/kg/day)

 

Systemic LOAEL = 15000 ppm (equivalent to 807.7 

mg/kg/day) based on decreased body-weight gain 

and decreased food consumption. 

Immunotoxic NOAEL = 15000 ppm (equivalent to 

807.7 mg/kg/day). 

The Immunotoxicity LOAEL was not established.
Propamocarb-HCl Human-Health Risk Assessment DP# 367968

Page 38 of 38

Appendix B. Physical/Chemical Properties

Table B.1. Physicochemical Properties of the Technical Grade Propamocarb-HCl.

Parameter Value Reference

Melting range 45-64°C DP# D267921, J. Tyler, 

2/20/04 pH 4.7

Density 1.083 g/mL

Water solubility (20°C) 1005 g/L

Solvent solubility (mg/L 20°C to 25°C) Dichloromethane > 4.3 x 105

Hexane <100 

Toluene <100

Methanol >7 x 105

Ethyl Acetate 2.3 x 104

Vapor pressure (25°C) 0.87 mPa 

Dissociation constant, pKa 9.29

Octanol/water partition coefficient, log POW

(20°C)

-2.6 (pH 4.1)

UV/visible absorption spectrum Not available