Mandipropamid Risk Assessment Document DP Number: 374096 

PC Code: 036602 

_____________________________________________________________________________________________ 

Page 1 of 15 

 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

 OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

MEMORANDUM

Date: 27-April-2010 

SUBJECT: Mandipropamid; Human Health Risk Assessment for the Section 18 Use on 

Basil. 

PC Code: 036602 DP Number: 374096 

Decision No.: 421080 Registration No.: 100-1254 

Petition No.: 09IL01 Regulatory Action: Section 18 

Risk Assessment Type: Single Chemical, 

Aggregate 

Case No.: NA 

TXR No.: Not Applicable CAS No.: 374726-62-2 

MRID No.: None 40 CFR: §180.637 

 

FROM: Roger Chesser, Biologist 

 ARIA/RIMUERB/RD (7505P) 

 

THROUGH: Breann Hanson, Biologist 

 ARIA/RIMUERB/RD (7505P) 

 

 Michael A. Doherty, Ph.D., Chemist 

Registration Action Branch 2 (RAB2) 

 Health Effects Division (HED; 7509P) 

TO: Barbara Madden 

 ARIA/RIMUERB/RD (7505P) 
Mandipropamid Risk Assessment Document DP Num: 374096 

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Table of Contents

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

2.0 Ingredient Profile.............................................................................................................. 4 

2.1 Structure and Nomenclature ............................................................................... 4 

2.2 Physical and Chemical Properties....................................................................... 5 

2.3 Summary of Proposed Uses.................................................................................. 5 

3.0 Hazard Characterization/Assessment............................................................................. 6 

3.1 Endocrine Disruption ........................................................................................... 7 

4.0 Public Health and Pesticide Epidemiology Data............................................................ 8 

5.0 Dietary Exposure/Risk Characterization ....................................................................... 8 

5.1 Pesticide Residue Profile ...................................................................................... 8 

5.2 Dietary Exposure and Risk ................................................................................ 10 

6.0 Residential and Other Exposures (Spray Drift, etc.)................................................... 11 

7.0 Aggregate Risk Assessments and Risk Characterization............................................ 12 

8.0 Cumulative Risk Characterization/Assessment........................................................... 12 

9.0 Occupational Exposure/Risk Pathway.......................................................................... 12 

9.1 Short-/Intermediate-Term Occupational Handler Risk.................................. 13 

9.2 Short-/Intermediate-Term Occupational Post-application Risk.................... 13 

10.0 References:....................................................................................................................... 14 

Appendix A: Tolerance Setting ................................................................................................. 15 

Appendix B: Review of Human Research ................................................................................ 15 
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1.0 Executive Summary

The Illinois Department of Agriculture has declared a crisis Section 18 exemption allowing the 

use of mandipropamid (as RevusTM Fungicide, EPA Reg. No. 100-1254) on basil to control 

downy mildew. Basil is harvested many times during the season, and the use of RevusTM 

Fungicide will extend the growing season until the first frost, approximately six additional 

weeks. The previous risk assessment conducted for mandipropamid was completed in 

conjunction with its registration for use on tobacco (DP Num; 365919, D. Rate, 8/JUL/2009). 

Mandipropamid is a fungicide in the mandelamide class developed by Syngenta Crop Protection, 

Inc. for the control of foliar oomycete pathogens in a range of crops including Plasmopara 

viticola in grapes, Phytophthora infestans in potatoes and tomatoes, and Pseudoperonospora 

cubensis in cucurbits. 

 

The product requested for emergency use is RevusTM Fungicide (EPA Reg. No. 100-1254). The 

use pattern summary is taken from draft Section 18 labeling and the RevusTM product label. 

Revus is a liquid formulation which contains 2.08 lb ai (23.3%) mandipropamid per gallon. The 

product is proposed for multiple foliar applications using ground, chemigation, or aerial 

equipment at a maximum seasonal rate of 32 fluid oz formulation/A/season or 4 

applications/A/season at the maximum rate of application. The proposed preharvest interval 

(PHI) is 7 days. 

For the purposes of this Section 18, the toxicology data base is adequate. Mandipropamid has 

low or minimal acute toxicity via the oral (Category IV), dermal (Category IV), and inhalation 

routes of exposure (Category IV). It is minimally irritating to the eye (Category IV), nonirritating to the skin (Category IV) and is negative for skin sensitization. Liver toxicity was the 

primary effect and was observed in rats, mice and dogs. There was no evidence of increased 

neonatal sensitivity in the developmental and reproduction toxicity studies, and no evidence of 

developmental effects, neurotoxicity, mutagenicity or carcinogenicity after exposure to 

mandipropamid. The FQPA Safety Factor (SF) has been reduced to 1X. 

Based on the available data, there are no effects attributable to a 1-day exposure to 

mandipropamid which are appropriate for assessing acute risks. Similarly, there are no effects 

attributable to dermal exposure. Therefore, only inhalation and chronic dietary points of 

departure have been selected. 

No data depicting residues of mandipropamid in/on basil are available at this time. ARIA 

translated residue data from vegetables, leafy (Crop Group 4) to derive an appropriate tolerance 

level for basil, fresh, and used maximum theoretical concentration factors (12X) for 

recommending a conservative tolerance for basil, dried. 

A screening-level dietary assessment (food + drinking water), based on tolerance-level residues 

and 100% of crops treated, indicates that chronic dietary risks are below OPP’s level of concern 

for all population subgroups. There are no uses of mandipropamid that would result in 

residential exposure that OPP can assess; therefore, there are no aggregate risks of concern 
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either. Occupational risk estimates associated with this emergency exemption are also below 

OPP’s level of concern. 

No risks of concern have been identified for the emergency exemption use of mandipropamid on 

basil; therefore, ARIA recommends for granting the exemption and establishing time-limited 

tolerances for residues of mandipropamid in/on basil, fresh at 20 ppm and basil, dried at 240 

ppm. 

Environmental Justice 

Potential areas of environmental justice concern, 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://homer.ornl.gov/nuclearsafety/nsea/oepa/guidance/justice/eo12898.pdf). 

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

subgroups according to well-established procedures. In line with OPP policy (as it relates to an 

imported crop), ARIA estimates risks to population subgroups from pesticide exposures that are 

based on patterns of that subgroup’s food consumption. Extensive data on food consumption 

patterns are compiled by the USDA under the Continuing Survey of Food Intake by Individuals 

(CSFII) and are used in pesticide risk assessments for all proposed/registered food 

uses/tolerances 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. Further considerations are currently in 

development as OPP has committed resources and expertise to the development of specialized 

software and models that consider exposure from traditional dietary patterns among specific 

subgroups. 

Human Data 

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 studies (listed in Appendix B) have 

been determined to require a review of their ethical conduct, and have received that review. 

2.0 Ingredient Profile 

The chemical structure and nomenclature of mandipropamid are presented in Table 2.1. The 

physicochemical properties of the technical grade mandipropamid are presented in Table 2.2. 

Mandipropamid is a fungicide in the mandelamide class developed by Syngenta Crop Protection, 

Inc. for the control of foliar oomycete pathogens in a range of crops. A summary of the 

proposed uses is presented in Table 2.3. 

2.1 Structure and Nomenclature
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Table 2.1. Test Compound Nomenclature. 

Compound 

Common name Mandipropamid

Cl

O

CH

O

N

H

O

CH3

O

CH

Company experimental name NOA 446510 

IUPAC name (RS)-2-(4-chloro-phenyl)-N-[2-(3-methoxy-4-prop-2-ynyloxy-phenyl)-ethyl]-2-

prop-2-ynyloxy-acetamide 

CAS name 4-chloro-N-[2-[3-methoxy-4-(2-propynyloxy)phenyl]ethyl]-α-(2-propynyloxy)- 

benzeneacetamide 

CAS registry number 374726-62-2 

End-use product (EP) RevusTM (2.08 lb/gal; EPA Reg. No. 100-1254), (Alternate Brand Name: Mandy 

Flowable Fungicide) 

2.2 Physical and Chemical Properties 

Table 2.2. Physical and chemical Properties of the Technical Grade of Mandipropamid. 

Parameter Value Reference 

Melting point/range 96.4-97.3oC 

Molecular formula/weight C23H22ClNO4 / 411.9 

pH 6-8 at 25oC (1% aqueous dispersion) 

Density 1.24 x 103 kg/m3 at 22oC 

Water solubility (25°C) 4.2 mg/L 

Solvent solubility (25°C) n-hexane 42 mg/L 

n-octanol 4.8 g/L 

toluene 29 g/L 

methanol 66 g/L 

ethyl acetate 120 g/L 

acetone 300 g/L 

dichloromethane 400 g/L 

Vapor pressure <9.4 x 10-7 Pa at 25°C or <7.0 x 10-9 mmHg 

Dissociation constant, pKa No dissociation constant in the pH range of 1 to 

12 

Octanol/water partition coefficient, 

Log(POW) 

3.3 at 25oC 

MRID 46800006 

(100-REIR.doc, S. 

Mathur, 

22/MAY/2007) 

2.3 Summary of Proposed Uses

Table 2.3. Details of Proposed Uses of 2.08 lb ai/gal FlC (RevusTM) on Basil. 

Application Timing, 

Type, and Equipment 

Maximum Single 

Application Rate 

(lb ai/A) 

Maximum Number 

of Applications per 

Season 

Maximum Seasonal 

Application Rate 

(lb ai/A) 

PHI 

(days) 
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Table 2.3. Details of Proposed Uses of 2.08 lb ai/gal FlC (RevusTM) on Basil. 

Application Timing, 

Type, and Equipment 

Maximum Single 

Application Rate 

(lb ai/A) 

Maximum Number 

of Applications per 

Season 

Maximum Seasonal 

Application Rate 

(lb ai/A) 

PHI 

(days) 

Basil 

0.13 4 0.52 7 

Postemergence 

Foliar spray 

Ground, aerial, or 

Chemigation 

Use Directions and Restrictions: Begin applications prior to disease development and 

continue throughout the season on a 7-10 day interval. Make no more than 2 consecutive 

applications before switching to an effective non-Group 40 fungicide. May be tank 

mixed with another fungicide labeled for downy mildew that has a different mode of 

action. The addition of a spreading/penetrating type adjuvant such as a non-ionic based 

surfactant or blend may improve activity. 

The supplemental label for RevusTM is adequate to allow evaluation of the residue data relative to 

the proposed uses on basil. 

3.0 Hazard Characterization/Assessment 

No changes have been made in the ingredient profile of mandipropamid since the previous risk 

assessment. Please refer to the previous risk assessment for detailed hazard characterization for 

mandipropamid (DP Num; 365919, D. Rate, 8/JUL/2009). 

HED previously recommended that the FQPA Safety Factor (SF) be reduced to 1X because there 

is no evidence of increased susceptibility, there are no/low concerns and no residual uncertainties 

regarding pre- and/or postnatal toxicity, there is no evidence of neurotoxicity in the database and 

a DNT study is not required. Although the data base is missing the immunotoxicity study as per 

the revised 40 CFR§158 (FR/Vol. 72, No. 207), the toxicological database is adequate for risk 

assessment and based on available toxicity data, there is no need for an additional uncertainty 

factor while the immunotoxicity study is completed. The overall weight of evidence in terms of 

hematology, clinical chemistry, organ weights, and/or histopathology suggests that 

mandipropamid does not directly target the immune system. Therefore ARIA does not believe 

that conducting a functional immunotoxicity study will result in a lower point of departure 

(POD) than currently selected for overall risk assessment, and therefore, a database uncertainty 

factor (UFDB) is not needed to account for the lack of this study. Furthermore, the exposure 

assessments are based on reliable data and reasonable worst-case assumptions and will not likely 

underestimate risks. 

Table 3.1a Toxicological Doses and Endpoints for Mandipropamid for Use in Dietary and Non-Occupational 

Human Health Risk Assessments 

Exposure/ 

Scenario 

Point of 

Departure 

Uncertainty/ 

FQPA Safety 

Factors 

RfD, PAD, Level of 

Concern for Risk 

Assessment 

Study and Toxicological Effects 

Acute Dietary 

(General 

Population, 

including Infants 

and Children) 

N/A N/A N/A No appropriate endpoint was 

identified, and a risk assessment was 

not conducted.
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Table 3.1a Toxicological Doses and Endpoints for Mandipropamid for Use in Dietary and Non-Occupational 

Human Health Risk Assessments 

Exposure/ 

Scenario 

Point of 

Departure 

Uncertainty/ 

FQPA Safety 

Factors 

RfD, PAD, Level of 

Concern for Risk 

Assessment 

Study and Toxicological Effects 

Acute Dietary 

(Females 13-49 

years of age) 

N/A N/A N/A No appropriate endpoint was 

identified, and a risk assessment was 

not conducted. 

Chronic Dietary 

(All 

Populations) 

NOAEL = 5 

mg/kg/day 

UFA = 10X 

UFH = 10X 

FQPA SF = 1X 

Chronic RfD = 0.05 

mg/kg/day 

cPAD = 0.05 

mg/kg/day 

Chronic toxicity – dogs

LOAEL = 40 mg/kg/day, based on 

evidence of liver toxicity (increased 

incidence and severity of microscopic 

pigment in the liver and increased 

alkaline phosphatase activity in both 

sexes as well as increased alanine 

aminotransferase activity in males). 

Cancer (oral, 

dermal, 

inhalation) 

“Not Likely to be Carcinogenic to Humans.” No treatment-related tumors observed in 

carcinogenicity studies in rats and mice. A cancer risk assessment was not conducted, the chronic 

risk assessment would be protective of any cancer effects. 

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 (c = chronic). RfD = reference dose. N/A = not applicable. 

Table 3.1b Summary of Toxicological Doses and Endpoints for Mandipropamid for Use in Occupational 

Human Health Risk Assessments 

Exposure/ 

Scenario 

Point of 

Departure 

Uncertainty 

Factors 

Level of Concern 

for Risk 

Assessment 

Study and Toxicological Effects 

Dermal (1-30 

days) and 

Intermediateterm (1-6 

months) 

N/A N/A N/A No appropriate endpoint was 

identified, and a risk assessment 

was not conducted.

28-day dermal toxicity study – rat, 

no systemic or dermal effect up to the 

limit dose of 1000 mg/kg/day; there 

were no neurotoxicity or 

developmental concerns. 

Inhalation 

Short-(1-30 

days) and 

Intermediateterm (1-6 

months) 

NOAEL = 

41 mg/kg/day 

IAF=100% 

UFA = 10X 

UFH = 10X 

Residential LOC for 

MOE = 100 

90-day oral toxicity – rats

LOAEL = 260 mg/kg/day, based on 

decreased body weights, body weight 

gains and food utilization in males 

and slight hepatotoxicity in both 

sexes. 

Cancer (oral, 

dermal, 

inhalation) 

“Not Likely to be Carcinogenic to Humans.” No treatment-related tumors observed in 

carcinogenicity studies in rats and mice. A cancer risk assessment was not conducted, the 

chronic risk assessment would be protective of any cancer effects. 

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 (intra-species). MOE = margin 

of exposure. LOC = level of concern. N/A = not applicable. IAF=inhalation absorption factor. 

3.1 Endocrine Disruption 

As required under FFDCA section 408(p), EPA has developed the Endocrine Disruptor 

Screening Program (EDSP) to determine whether certain substances (including pesticide active 

and other ingredients) may have an effect in humans or wildlife similar to an effect produced by 
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a “naturally occurring estrogen, or other such endocrine effects as the Administrator may 

designate.” The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine related effects caused by the substance, and 

establish a dose-response relationship between the dose and the E, A, or T effect. 

Between October 2009 and February 2010, EPA issued test orders/data call-ins for the first 

group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. 

This list of chemicals was selected based on the potential for human exposure through pathways 

such as food and water, residential activity, and certain post-application agricultural scenarios. 

This list should not be construed as a list of known or likely endocrine disruptors. 

Mandipropamid is not among the group of 58 pesticide active ingredients on the initial list to be 

screened under the EDSP. Under FFDCA sec. 408(p) the Agency must screen all pesticide 

chemicals. Accordingly, EPA anticipates issuing future EDSP test orders/data call-ins for all 

pesticide active ingredients. 

For further information on the status of the EDSP, the policies and procedures, the list of 67 

chemicals, the test guidelines and the Tier 1 screening battery, please visit our website: 

http://www.epa.gov/endo/. 

4.0 Public Health and Pesticide Epidemiology Data 

Based on the recent registration of this chemical, usage patterns and the lack of residential use 

sites, no incident reports are expected at this time. Additionally, no public health or 

epidemiology data were found for this chemical when searched in the National Library of 

Medicine TOXNET databases. 

5.0 Dietary Exposure/Risk Characterization

5.1 Pesticide Residue Profile 

The nature of the residue for mandipropamid is adequately understood for purposes of tolerance 

enforcement and risk assessment, and the residues of concern are summarized in Table 5.1.1. A 

tolerance-enforcement method, based on the German Multi-residue Method DFG S-19, is 

available and has been validated for a number of plant commodities. The method is expected to 

be suitable for analysis of basil. 

Table 5.1.1. Summary of Metabolites and Degradates to be Included in the Risk Assessment and Tolerance 

Expression. 
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Matrix Residues included in Risk 

Assessment 

Residues included in 

Tolerance Expression 

Primary Crop Parent mandipropamid 

(Parent + SYN 500003 for 

root and tuber vegetables ) 

Plants Parent mandipropamid 

Rotational Crop Not applicable Parent mandipropamid* 

Livestock Ruminant Not applicable Not applicable 

Poultry Not applicable Not applicable 

Drinking Water Parent, SYN 504851 and 

SYN 500003* 

Not Applicable 

*Although the parent compound is a residue of concern in rotational crops, tolerances are not needed for the present 

uses, based on the absence of residues in the field rotational crops study following the label’s 30 day plantback 

interval. 

There are no data available depicting residues of mandipropamid in fresh or dried basil. As a 

surrogate, ARIA had translated data from vegetables, leafy (Crop Group 4) (Table 5.1.2). These 

data support the recommended tolerance of 20 ppm in/on fresh basil. A conservative tolerance 

of 240 ppm in/on basil, dried is recommended to accommodate a maximum theoretical 

concentration factor of 12X. 

Table 5.1.2. Summary of Residue Chemistry Considerations 

Parameter Proposed Use on Basil Translated Residue Data from 

Leafy Vegetables 

Chemical Mandipropamid Mandipropamid 

Formulation RevusTM RevusTM 

Crop Basil Leafy vegetable 

Type of Application Ground, Aerial, Chemigation Ground, Aerial, Chemigation 

Number of Applications 4 4 

Timing/Retreatment Interval Post emergent foliar spray Post emergent foliar spray 

Individual Application Rate 0.13 lb ai/A 0.13 lb ai/A 

Seasonal Application Rate 0.52 lb ai/A 0.52 lb ai/A 

Pre-harvest Interval 7 day 1 day 

Maximum Residue --- 12.8 ppm 

Restrictions Non-ionic surfactant may be used. Non-ionic surfactant may be used. 

Residue Data Source Section 18 09IL01 DP#328534, D. McNeilly, 

08/28/2007 

Performing Laboratory Not Applicable Field Trial Studies 

There are no specific Codex, Canadian, or Mexican maximum residue limits (MRLs) for 

mandipropamid. 

The maximum seasonal application proposed for the Section 18 use on basil is less than or equal 

to currently registered use rates. As such, a previously modeled Tier I drinking water assessment 
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conducted by EFED for the established mandipropamid uses(DP Num: 339258, I. Abdel-Saheb, 

23/APR/2007) was used in this assessment. The assessment included mandipropamid and its 

major aquatic degradates (SYN 500003 and SYN 5044851) in drinking water. The estimated 

drinking water concentrations (EDWCs) are based on the highest labeled use pattern of 4 

applications of 0.13 lbs ai/A for a total rate of 0.52 lbs ai/A/Season. The modeled EDWCs are 

shown in the Table 5.1.3. The EDWC used in the dietary analysis is 36.5 ppb, the sum of the 

surface water numbers for Mandipropamid, SYN500003, and SYN504851. 

Table 5.1.3. Estimated Drinking Water Concentrations for Mandipropamid and Metabolites for Chronic 

Dietary Analysis 

Mandipropamid 

 (ppb) 

SYN500003 

 (ppb) 

SYN504851 

 (ppb) 

Surface Water 25.2 2.32 8.99 

Ground Water 5.22E-02 5.85E-01 1.73 

Four applications at 

0.13 lb ai/A with 7 

days between 

applications 

Note: The chronic drinking water values were incorporated directly into the dietary assessments under the DEEMFCID food categories “water, all sources” and “water, indirect, all sources.” 

5.2 Dietary Exposure and Risk

A chronic dietary risk assessment was conducted using the Dietary Exposure Evaluation Model 

(DEEM-FCIDTM, Version 2.03) which uses food consumption data from the USDA’s Continuing 

Surveys of Food Intakes by Individuals (CSFII) from 1994-1996 and 1998. 

No acute dietary endpoint could be identified based on the toxicology data currently available for 

mandipropamid and mandipropamid is classified as not likely to be a human carcinogen. 

Therefore, acute and cancer risks are not of concern. 

A tolerance level (unrefined) chronic exposure assessment that assumes 100% crop treated was 

conducted for the registered and proposed Section18 uses of mandipropamid. The DEEM 

analysis incorporates estimates of drinking water concentrations from EFED directly into the 

analysis. The chronic dietary exposure analysis for mandipropamid results in dietary risk 

estimates for food and water that are below the Agency’s level of concern for chronic dietary 

exposure. For mandipropamid, the DEEM chronic dietary exposure estimate was 26% of the 

cPAD for the U.S. population and was 44% of the cPAD for the highest exposed population 

subgroup, children 1-2 years of age. 

Table 5.2. Results of Chronic Dietary Exposure Analysis Using DEEM FCID.1 

Chronic Dietary Cancer 

Population Subgroup Dietary Exposure 

(mg/kg/day) % cPAD 

Dietary 

Exposure 

(mg/kg/day) 

Risk 

General U.S. Population 0.012927 26 

All Infants (< 1 year old) 0.009489 19 

Children 1-2 years old 0.022136 441 

Children 3-5 years old 0.019329 39 

Children 6-12 years old 0.013175 26 

Youth 13-19 years old 0.010474 21 

N/A N/A 
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Table 5.2. Results of Chronic Dietary Exposure Analysis Using DEEM FCID.1 

Chronic Dietary Cancer 

Population Subgroup Dietary Exposure 

(mg/kg/day) % cPAD 

Dietary 

Exposure 

(mg/kg/day) 

Risk 

Adults 20-49 years old 0.012470 25 

Adults 50+ years old 0.012470 25 

Females 13-49 years old 0.012212 24 1

The population subgroup with the highest estimated chronic dietary (food + drinking water) exposure and 

risk is indicated by bold text. 

Note: % cPAD reported to 2 significant figures. 

6.0 Residential and Other Exposures (Spray Drift, etc.)

Residential exposures were not assessed because the registered and proposed uses of 

mandipropamid do not involve applications by homeowners or by commercial applicators in 

residential settings. 

Based on the available toxicity database and the Agency's current practices, a quantitative 

postapplication inhalation exposure assessment was not performed for mandipropamid at this 

time primarily because it has a low vapor pressure (<7.0 x 10-9 mmHg) and it is applied at a 

relatively low rate. However, volatilization of pesticides may be a potential source of 

postapplication inhalation exposure to individuals nearby to pesticide applications. The Agency 

sought expert advice and input on issues related to volatilization of pesticides from its Federal 

Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009. 

The Agency 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 put into place, the 

Agency may revisit the need for a quantitative postapplication inhalation exposure assessment 

for mandipropamid. 

Spray drift is always a potential source of exposure to residents near 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 mandipropamid. 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 

management practices. 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 drift management practices to reduce 

off-target drift with specific products with significant risks associated with drift. 
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7.0 Aggregate Risk Assessments and Risk Characterization

In accordance with the FQPA, ARIA must consider and aggregate (add) 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, ARIA considers both the route and 

duration of exposure. 

There are no residential uses proposed or registered for mandipropamid, and therefore aggregate 

risk is equal to that from consumption of food and water. Chronic aggregate risk estimates 

associated with exposure to mandipropamid residues in food and water do not exceed ARIA’s 

level of concern. See section 5.2 for additional details. Acute and cancer aggregate risks are not 

of concern due to the absence of an acute dietary endpoint and because mandipropamid is not 

likely to be carcinogenic. 

8.0 Cumulative Risk Characterization/Assessment

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

modify, or revoke a tolerance, the Agency consider "available information concerning the 

cumulative effects” of a particular pesticide's residues and "other substances that have a common 

mechanism of toxicity.” 

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 mandipropamid and any other substances, and mandipropamid does not appear to produce a 

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

therefore, EPA has not assumed that mandipropamid 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 Pathway 

Exposure to pesticide handlers is likely during the use of mandipropamid in a variety of 

occupational environments. The product may be applied using groundboom equipment, aerial 

equipment, chemigation, and airblast equipment (grapes only). 

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

following scenarios: (1) mixing/loading liquids for aerial applications; (2) mixing/loading liquids 

for chemigation applications; (3) mixing/loading liquids for groundboom applications; (4) 

mixing/loading liquids for airblast applications; (5) applying sprays with aerial equipment; (6) 

applying sprays with groundboom equipment; (7) applying sprays with airblast equipment; and 

(8) flagging for aerial spray applications. Occupational exposures are expected to be short- and 
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intermediate-term. ARIA does not expect long-term exposure due to the limited number of 

applications. 

9.1 Short-/Intermediate-Term Occupational Handler Risk 

Short- and intermediate-term dermal exposures and risks were not assessed for mandipropamid, 

since no short- or intermediate-term dermal endpoint was identified. Short-term and 

intermediate-term inhalation risk assessments were completed based on the inhalation toxicity 

endpoint that was identified. Long-term handler exposures are not expected to occur based on 

the uses of mandipropamid. 

 

Daily Exposure: Daily inhalation handler exposures are estimated for each applicable handler 

task with the application rate, the area treated in a day, and the applicable inhalation unit 

exposure. The daily inhalation dose is calculated by normalizing the daily inhalation exposure 

by body weight and adjusting with an appropriate inhalation absorption factor. 

Daily Dose: The daily inhalation dose is calculated by normalizing the daily inhalation exposure 

by body weight and adjusting with an appropriate inhalation absorption factor. 

Margins of Exposure: Non-cancer inhalation risks for each applicable handler scenario are 

calculated using a Margin of Exposure (MOE), which is a ratio of the daily dose to the relevant 

toxicological points of departure. 

All short- and intermediate-term inhalation risk estimates meet or exceed the MOE of 100 at the 

baseline level of mitigation. This indicates that occupational inhalation risks are not of concern. 

A summary of the short- and intermediate-term inhalation risk estimates for each exposure 

scenario is presented below in Table 9.1. 

Table 9.1. Summary of Exposure & Risk to Occupational Handlers From Mandipropamid.

Unit Exposure1 

mg ai/lb handled 

Applic. 

Rate2 

lb ai/unit 

Units 

Treated3

Avg. Daily Exposure4 

mg ai/kg bw/day 

MOE5

Mixer/Loader - Liquid - Open Pour

Inhalation 0.0012 0.13 lb ai/A 350 A/day Inhalation 0.00078 53,000 

Applicator - Air-blast - Open Cab

Inhalation 0.0045 0.13 lb ai/A 40 A/day Inhalation 0.00033 124,000 

Aerial Applicator (Pilots not required to wear gloves) 

Inhalation 0.000068 0.13 lb ai/A 350 A/day Inhal. 0.000044 932,000 

1. Unit Exposures are taken from “PHED SURROGATE EXPOSURE GUIDE”, Estimates of Worker Exposure from The 

Pesticide Handler Exposure Database Version 1.1, August 1998. Dermal = Single Layer Work Clothing No Gloves; Single 

Layer Work Clothing With Gloves; Inhal. = Inhalation. Units = mg a.i./pound of active ingredient handled. Data Confidence: 

LC = Low Confidence, MC = Medium Confidence, HC = High Confidence. 

2. Applic. Rate. = Taken from draft supplemental label. 

3. Units Treated are taken from “Standard Values for Daily Acres Treated in Agriculture”; ExpoSAC SOP No. 9.1. Revised 5 

July 2000. 

4. Average Daily Dose = Unit Exposure * Applic. Rate * Units Treated ÷ 70 kg Body Weight. 

5. MOE = Margin of Exposure = NOAEL ÷ ADD. NOAEL for short- and intermediate-term duration inhalation exposure = 41 

mg ai/kg bw/day. 

9.2 Short-/Intermediate-Term Occupational Post-application Risk 
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Occupational post-application exposures/risks were not quantified because no appropriate dermal 

endpoints were identified. The 4-hr Restricted Entry Interval (REI) appearing on the product 

label for RevusTM Fungicide adequately supports the Worker Protection Standard (WPS). 

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

assessment was not performed for mandipropamid at this time primarily because it has a very 

low vapor pressure (<7.0 x 10-9 mmHg) and is applied at a very low rate. However, volatilization of 

pesticides may be a potential source of post-application inhalation exposure to individuals nearby 

to pesticide applications. The Agency sought expert advice and input on issues related to 

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

Scientific Advisory Panel (SAP) in December 2009. The Agency 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 put into place, the Agency may revisit the need for a quantitative post-application 

inhalation exposure assessment for mandipropamid. 

10.0 References: 

MANDIPROPAMID – Human Occupational Exposure/Risk Assessment for the Illinois Section 

18 Use of Mandipropamid on Basil, DP Num: 371728, M. Dow, 29/DEC/2009. 

MANDIPROPAMID – Exposure/Risk Assessment for the Proposed Uses of Mandipropamid on 

Brassica Vegetables, Bulb Vegetables, Cucurbits, Fruiting Vegetables, Leafy Green Vegetables, 

Grapes, Tomatoes, and Tuberous and Corm Vegetables, DP Num: 357873, M. Dow, 

28/OCT/2008. 

Mandipropamid. Section 3 Registration Request to Register New Uses on Hops and Tobacco. 

Summary of Analytical Chemistry and Residue Data. DP Num: 348229 and 352322, Debra 

Rate, 11/DEC/2008. 

Mandipropamid. Request to Register New Food/Feed Uses on Head and Stem Brassica, Leafy 

Brassica Greens, Cucurbit Vegetables, Fruiting Vegetables, Leafy Vegetables, Tuberous and 

Corm Vegetables, Grapes, and Onions (Dry Bulb and Green). Summary of Analytical Chemistry 

and Residue Data. Petition Numbers 6F7057 and 7F7184. DP Num: 340784, Dennis McNeilly, 

28/AUG/2007. 

Mandipropamid: Chronic Dietary (Food and Drinking Water) Exposure and Risk Assessment for 

Section 18 use of Mandipropamid to Basil. PC Code: 036602. DP Num: 371321. R. Chesser. 

12/JAN/2010. 

Mandipropamid: AMENDED Chronic Dietary (Food and Drinking Water) Exposure and Risk 

Assessment for Section 18 use of Mandipropamid to Basil. PC Code: 036602. DP Num: 

376967. R. Chesser. 27/APR/2010. 
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Appendix A: Tolerance Setting 

Table A.1. Tolerance Summary for Mandipropamid. 

Commodity Proposed 

Tolerance (ppm) 

Recommended 

Tolerance (ppm) 

Comments; Correct Commodity Definition

Proposed Time-limited Tolerances 

Basil, fresh --- 20 Recommended tolerance translated from 

vegetables, leafy (Crop Group 4). 

Basil, dried --- 240 Recommended tolerance for basil, fresh, 

multiplied by a maximum theoretical 

concentration factor of 12X. 

Appendix B: Review of Human Research 

The PHED Task Force, 1995. The Pesticide Handlers Exposure Database, Version 1.1. Task 

Force members Health Canada, U.S. Environmental Protection Agency, and the National 

Agricultural Chemicals Association, released February, 1995.