Mancozeb Human Health Risk Assessment OP Nos. 411742 and 411764 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

Date: May 14, 2013 

OFFICE OF 

CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

SUBJECT: Mancozeb: Human Health Risk Assessment to Support Proposed New 

Section 3 Uses on Walnuts and Tolerances for Imported Tangerines 

PC Code: 014504 DP Barcode: 0411742; 0411764 

Decision No.: ~{,ft/1, /ff!OP1 Registration No.: 70506-185, 70506-194, 

70506-234, 70506-236 

Petition No.: I F7935, 2E8062 Re2ulatorv Action: Section 3 

Risk Assessment Type: Single Chemical Aggregate Case No.: 0643 

TXRNo.: NA CAS No.: 8018-01-7 

MRIDNo.:NA 40 CFR: 180.176 

.... -

FROM: Danette Drew, Chemist/Risk Asss p .. ~ 

Pete 

Ana Rivera-Lupiafiez Savoia, Chemist ~p

1 

emist '_..l ~ .' _ 

Linda Taylor, Ph.D., oxicologist ~/~~ (..._ 

Risk Assessment Branch V and VII 

Health Effects Division (7509P) 

THROUGH: Michael 

R1sk Assessment 

Metzger, 

Branch 

Branch 

V 

Chi

an

) 

J<l...fi 

{/~J ~f / { 

Health Effects Division (7509P) 

TO: Heather Garvie, Risk Manager 

Tamue Gibson, Risk Manager 

Fungicide Branch 

Registration Division (7505P) 

Attached please find the human health risk assessment for the active ingredient mancozeb to support 

requested new uses on walnuts and to support import tolerances for the use on mandarin oranges 

(tangerines). This document supersedes the 4/10/13 document 0397268, Mancozeb: Human Health Risk 

Assessment to Support Proposed New Section 3 Uses on Walnuts and Tolerances for Imported 

Tangerines. This document addresses risks from exposure to mancozeb and mancozeb-derived 

ethylenethiourea (ETU) only. A separate assessment addressing risk from ETU derived from all ethylene 

bisdithiocarbamate (EBDC) pesticides is forthcoming. 

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Mancozeb Human Health Risk Assessment DP Nos. 411742 and 411764

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1.0 Executive Summary............................................................................................................. 4

2.0 HED Recommendations....................................................................................................... 9

2.1 Data Deficiencies ............................................................................................................. 9

2.2 Tolerance Considerations................................................................................................. 9

2.2.1 Enforcement Analytical Method............................................................................... 9

2.2.2 Recommended Tolerances...................................................................................... 10

2.2.3 Revisions to Petitioned-For Tolerances.................................................................. 10

2.2.4 International Harmonization ................................................................................... 11

2.3 Label Recommendations................................................................................................ 11

2.3.1 Recommendations from Residue Reviews ............................................................. 11

2.3.2 Recommendations from Occupational Assessment................................................ 11

2.3.3 Recommendations from Residential Assessment ................................................... 11

3.0 Introduction........................................................................................................................ 12

3.1 Chemical Identity ........................................................................................................... 12

3.2 Physical/Chemical Characteristics................................................................................. 12

3.3 Pesticide Use Pattern...................................................................................................... 12

3.4 Anticipated Exposure Pathways..................................................................................... 14

3.5 Consideration of Environmental Justice ........................................................................ 14

4.0 Hazard Characterization and Dose-Response Assessment................................................ 15

4.1 Summary of Toxicological Effects ................................................................................ 15

4.2 Safety Factor for Infants and Children (FQPA Safety Factor)....................................... 18

4.2.1 Completeness of the Toxicology Database............................................................. 19

4.2.2 Evidence of Neurotoxicity ...................................................................................... 19

4.2.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal ......... 19

4.2.4 Residual Uncertainty in the Exposure Database..................................................... 20

4.3 Toxicity Endpoint and Point of Departure Selections.................................................... 21

5.0 Dietary Exposure and Risk Assessment ............................................................................ 28

5.1 Residues of Concern Summary and Rationale............................................................... 28

5.2 Food Residue Profile...................................................................................................... 29

5.3 Water Residue Profile .................................................................................................... 30

5.4 Dietary Risk Assessment................................................................................................ 31

5.4.1 Description of Residue Data Used in Dietary Assessment..................................... 31

5.4.2 Percent Crop Treated Used in Dietary Assessment ................................................ 32

5.4.3 Acute Dietary Risk Assessment.............................................................................. 32

5.4.4 Chronic Dietary Risk Assessment .......................................................................... 33

5.4.5 Cancer Dietary Risk Assessment............................................................................ 33

5.4.6 Summary Table....................................................................................................... 33

6.0 Residential (Non-Occupational) Exposure/Risk Characterization ...................................... 34

6.1 Residential Handler Exposure........................................................................................ 35

6.2 Post-Application Exposure............................................................................................. 41
Mancozeb Human Health Risk Assessment DP Nos. 411742 and 411764

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6.2.1 Home Garden Post-application Scenarios .............................................................. 44

6.2.2 Treated Turf Post-application Scenarios................................................................. 45

6.3 Residential Risk Estimates for Use in Aggregate Assessment ...................................... 47

6.4 Residential Bystander Post-application Inhalation Exposure ........................................ 49

6.5 Spray Drift...................................................................................................................... 49

7.0 Aggregate Exposure/Risk Characterization.......................................................................... 50

7.1 Acute Aggregate Risk .................................................................................................... 51

7.2 Short-Term Aggregate Risk......................................................................................... 51

7.3 Intermediate-Term Aggregate Risk................................................................................ 53

7.4 Long-Term or Chronic Aggregate Risk ......................................................................... 53

7.5 Cancer Aggregate Risk................................................................................................... 53

8.0 Cumulative Exposure/Risk Characterization....................................................................... 54

9.0 Occupational Exposure/Risk Characterization ..................................................................... 54

9.1 Short- and Intermediate-Term and Cancer Handler Risk............................................... 55

9.2 Short- and Intermediate-Term and Cancer Post-Application Risk ................................ 65

9.2.1 Dermal Post-Application Risk ................................................................................ 65

9.2.2 Inhalation Postapplication Risk .............................................................................. 67

10.0 References.......................................................................................................................... 68

Appendix A. Toxicology Profile and Executive Summaries....................................................... 69

Appendix B. Physical/Chemical Properties................................................................................. 76

Appendix C. Review of Human Research ................................................................................... 77
Mancozeb Human Health Risk Assessment DP Nos. 411742 and 411764

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1.0 Executive Summary

Background

The Registration Division (RD) requested that the Health Effects Division (HED) conduct a

human health risk assessment to support 1) a petition for the proposed use of the fungicide 

mancozeb on walnuts (PP#1F7935) and 2) a petition to support the establishment of a tolerance 

for residues of mancozeb on imported tangerines (PP#2E8062).

There are four United Phosphorus mancozeb end-use products relevant to the petition for treating 

walnuts. These products are: Penncozeb 75DF (EPA Reg. No. 70506-185), Manzate Pro-Stick 

Fungicide (EPA Reg. No. 70506-234), Penncozeb 4FL Flowable Fungicide (EPA Reg. No. 

70506-194), and Manzate Flowable (EPA Reg. No. 70506-236). The Dow mancozeb product 

proposed for treating tangerines grown in Korea is the Dithane® M45 Fungicide (EPA Reg. No. 

62719-387).

Mancozeb is a coordination product of zinc ion and maneb (manganese 

ethylenebisdithiocarbamate) used as a broad-spectrum fungicide in agriculture, professional turf 

management, and horticulture. In plants and livestock commodities, the residues of concern for 

risk assessment are mancozeb and its metabolite/degradate ethylenethiourea (ETU). The residue 

of concern in drinking water is ETU only. Tolerances are currently established for residues of 

mancozeb including its metabolites and degradates (measured as the degradate CS2) on a number 

of crop and livestock commodities.

Mancozeb is a fungicide in the class of ethylenebis dithiocarbamates (EBDC), which also 

includes the fungicides maneb and metiram; all of these compounds have a common 

metabolite/degradate, ethylenethiourea (ETU). Some of the more notable toxicity in the 

mancozeb studies was due to toxicity from its metabolite, ETU. Thyroid toxicity and 

developmental toxicity in rats were attributed to toxicity from ETU. Injury to peripheral nerves 

occurred in mancozeb toxicity studies but not in studies with ETU. Separate assessments are 

presented herein for 1) toxicity and exposure to parent mancozeb only and 2) toxicity and 

exposure to ETU derived from mancozeb, including combined exposures from both ETU as an 

environmental degradate and ETU as an in vivo metabolite. A separate assessment addressing 

risk from ETU derived from all ethylene bisdithiocarbamate (EBDC) pesticides, not just 

mancozeb, is forthcoming.

For residential, occupational and dietary exposures, including oral, dermal and inhalation routes 

of exposure, a 7.5% in vivo metabolic conversion of absorbed mancozeb to ETU has been used 

based on rat metabolism data, and has been accounted for in estimating total exposure (in vivo

metabolism and direct sources) to ETU. 

Mancozeb Toxicology

The findings in multiple studies demonstrate that the thyroid is a target organ for mancozeb. 

Thyroid toxicity was manifested as alterations in thyroid hormones, increased thyroid weight, 
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and microscopic thyroid lesions (mainly thyroid follicular cell hyperplasia). In a subchronic 

study in the rat, neuropathology was seen microscopically (injury to peripheral nerves) with 

associated clinical signs (abnormal gait and limited use of rear legs) and loss of muscle mass. 

Developmental defects in the rat developmental toxicity study included hydrocephaly, skeletal 

system defects, and other gross defects. Abortions occurred in the rabbit developmental toxicity 

study at the high dose.

The database for mancozeb is extensive and is sufficient for characterizing toxicity and hazard. 

Although most of the mancozeb risk assessment endpoints are of thyroid toxicity, a 

developmental thyroid toxicity study is not available. This datagap will be satisfied by an 

ongoing developmental thyroid toxicity study with ETU, which is part of an extended onegeneration reproductive toxicity (EOGRT) study on ETU. For mancozeb, the FQPA SF (safety 

factor) of 10X is retained for women of childbearing age (13- 49 years old) and for children less 

than 6 years old to account for the lack of data on the developing thyroid. The FQPA safety 

factor is reduced to 1X for other lifestages (children > 6 years, females > 49 years, and adult 

males), for which the thyroid is largely developed and there are applicable thyroid data.

The recently submitted immunotoxicity study has been reviewed and mancozeb did not show 

any immunotoxicity potential.

ETU Toxicology 

In addition to assessing risk from exposure to mancozeb, this assessment also considers risks 

from exposure to mancozeb-derived ETU. 

The toxicology database for mancozeb and ETU is sufficient for characterizing toxicity and 

hazard. HED has relied on a combination of guideline data and several studies in the open 

literature to assess hazard for ETU. The thyroid is a target organ for ETU. Thyroid toxicity in 

subchronic and chronic rat, mouse, and dog studies included decreased levels of T4, changes in 

T3 levels, compensatory increases in levels of TSH, increased thyroid weight, and microscopic 

thyroid changes, chiefly hyperplasia. Overt liver toxicity was observed in one chronic dog study.

Developmental defects in the rat developmental toxicity study were similar to those seen with 

mancozeb, and included hydrocephaly and related lesions, skeletal system defects, and other 

gross defects.

Toxicology data gaps for ETU include a 2-generation reproduction study in rats, a developmental 

neurotoxicity study in rats, and a developmental thyroid toxicity study in rats. These datagaps 

will be satisfied with the ongoing EOGRT study on ETU. The datagaps being addressed in the 

EOGRT study could affect women of childbearing age or the developing young, and the ETU 

FQPA SF of 10X is retained for females 13-49 years of age and for children less than 6 years of 

age. The FQPA safety factor for ETU is reduced to 1X for other lifestages (children > 6 years, 

females > 49 years, and adult males), for which the thyroid is largely developed and there are 

applicable thyroid data. Although there was fetal sensitivity for malformations in the ETU 

developmental rat studies, the endpoints that were selected are protective of these effects. 
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The recently submitted immunotoxicity study on ETU did not show any immunotoxicity 

potential.

Cancer

Mancozeb’s potential for carcinogenicity (as well as that of the other EBDCs) is assessed by the 

metabolite, ETU, which is classified as a probable human carcinogen (B2), with a cancer 

potency factor (Q1

*

) of 0.0601 (mg/kg/day)-1for risk assessment. On this basis, mancozeb 

cancer risk has been calculated by estimating exposure to mancozeb-derived ETU (including the 

metabolic conversion) and using the ETU cancer potency factor to provide a quantitative 

estimate of risk. 

Dietary Risk Assessments

Residues of mancozeb are not expected in ground or surface water. However, mancozeb’s 

metabolite, ETU, is highly water soluble and may reach both surface and ground water under 

some conditions. ETU surface water estimated drinking water concentrations (EDWCs) were 

based both on PRZM-EXAMS modeling information and available monitoring data. 

Probabilistic acute dietary exposure and risk assessments were conducted for mancozeb and ETU 

incorporating maximum percent crop treated or maximum projected percent crop treated 

information, field trial or monitoring data, and processing and cooking factors. No acute dietary 

(food and drinking water) risks of concern were identified for either mancozeb or mancozebderived ETU. 

The chronic dietary exposure and risk assessments (non-cancer and cancer) for mancozeb and 

mancozeb-derived ETU incorporated average values based either on field trial data or monitoring 

data and average percent crop treated data or average projected percent crop treated estimates, as 

well as processing and cooking factors. No chronic non-cancer dietary (food and drinking water) 

risks of concern were identified for mancozeb or mancozeb-derived ETU. The cancer risk 

estimate associated with exposure to ETU in food and water, as a result of established and 

proposed mancozeb uses, is 2 x 10-6for the general U.S. population.

Residential Exposure and Risk

No new residential uses are being added to the label as a result of the current actions; however, 

residential uses that could result in mancozeb and ETU exposure (i.e., home gardeners applying 

mancozeb to vegetables or entering treated gardens, and golfers contacting mancozeb treated turf 

after application) have been reassessed in this document to reflect updates to toxicology endpoint 

selections, updates to the Levels of Concern (LOCs), and updates to HED’s 2012 Residential 

SOPs.

Gardens

Residential handler risk estimates for adults applying mancozeb to gardens were assessed for 

mancozeb (inhalation only; dermal toxicity is not expected for mancozeb) and it’s degradate 
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ETU (combined dermal and inhalation). Non-cancer short-term assessments were performed for 

both mancozeb and ETU. There are no handler risk estimates of concern for adults applying 

mancozeb to home gardens. A cancer assessment was also performed for ETU. The cancer risks

for residential handlers are estimated in the 10-8range.

Residential post-application risk estimates were assessed for home gardeners (adults and youth) 

harvesting vegetables from treated gardens. As no dermal hazard was identified for mancozeb, a 

quantitative dermal post-application assessment (non-cancer/short-term and cancer) was only 

performed for its metabolite, ETU. Inhalation exposures are not expected for the postapplication activities. There are no non-cancer/short-term risk estimates of concern for adults or 

youth entering mancozeb treated home garden. Post-application cancer risk for adult home 

gardeners is estimated at 9 x 10

-7

.

Turf (Golf Courses)

Residential post-application risk estimates were assessed for adult and youth golfers contacting 

mancozeb treated turf after application. As no dermal hazard was identified for mancozeb, a 

quantitative dermal post-application assessment (non-cancer/short-term and cancer) was only 

performed for its metabolite, ETU. Inhalation exposures are not expected for the postapplication golfing activities. There are no non-cancer/short-term risk estimates of concern for 

adults or youth golfing on treated turf. The cancer risk to adult golfers is estimated at 3 x 10-8.

Aggregate Risk Assessments

HED conducted acute, short- term and chronic non-cancer aggregate assessments for mancozeb 

and mancozeb-derived ETU, as well as a cancer aggregate assessment for mancozeb-derived 

ETU. The aggregate assessments combined the residential scenarios that resulted in the highest 

estimated exposures with food and drinking water exposures. The garden scenarios resulted in 

higher post-application exposures than the golfing scenarios; aggregate assessments using the 

garden scenario are protective of any post-application exposures to adult and youth golfers. 

The acute and chronic non-cancer aggregate assessments include only dietary (food and drinking 

water) exposures. There are no acute or chronic aggregate risk estimates of concern.

The short-term aggregate assessment for mancozeb and ETU combined adult residential handler 

exposures and dietary (food only for mancozeb; food and water for ETU) exposures. There are 

no short-term aggregate risk estimates of concern for adults applying mancozeb to gardens.

A short-term aggregate assessment was performed for ETU for adults and youth entering treated 

gardens. Post-application exposures to ETU were combined with dietary (food and water) 

exposures. There are no short-term aggregate risk estimates of concern for adults or youth 

entering treated gardens.

The cancer aggregate assessment for mancozeb-derived ETU includes contributions from 

residential and dietary (food and water) exposures. The cancer aggregate risk estimates (handler 
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and post-application) for adults applying mancozeb to gardens or entering treated gardens are 2 x 

10-6and 3 x 10-6, respectively.

Occupational Exposure and Risk

Occupational assessments were performed for the proposed U.S. walnut use. An occupational 

assessment was not performed for the proposed use on imported tangerines.

Handler (Non-Cancer)

Occupational handler non-cancer (short- and intermediate-term) assessments were performed for

mancozeb and ETU exposures as a result of mancozeb applications to walnuts (i.e., during 

mixing, loading, and applying). A handler cancer assessment was also performed for ETU. Only 

inhalation exposures were considered for mancozeb because no effects were observed at the limit 

dose in a 28-day dermal rat study. In the case of ETU, however, inhalation and dermal 

exposures were considered for both the non-cancer and cancer risk assessments.

All mixer/loader non-cancer risk scenarios do not exceed HED’s level of concern (i.e., MOEs ≥ 

300 for mancozeb exposures and MOEs ≥1000 for ETU exposures) at some level of risk 

mitigation (e.g., gloves, respirators, or other engineering control measures). However, noncancer risks estimates for M/L scenarios using dry flowable (DF) formulations in support of

aerial applications to walnuts exceed HED’s level of concern for females age 13-49 years (i.e.,

MOE=260 for mancozeb inhalation exposures and MOE=750 for ETU exposures) at label PPE. 

It should be noted that no respiratory protection equipment or other engineering control measures

are requested on the DF labels. With the addition of a respirator, MOE=1300 for mancozeb 

inhalation exposures and MOE=2900 for ETU exposures for females 13-49 mixing and loading 

the DF formulation for aerial application to walnuts.

All application non-cancer risk scenarios do not exceed HED’s level of concern at some level of 

risk mitigation (e.g., gloves or other engineering control measures). Aerial and airblast

applicator risks do not exceed HED’s level of concern (i.e., MOEs ≥ 300 for mancozeb 

exposures and MOEs ≥1000 for ETU exposures) with engineering control (i.e., enclosed cockpit 

or closed cab). Mixer/loader/ applicators with mechanically pressurized handgun risks do not 

exceed HED’s level of concern at label PPE (i.e., gloves, no respirator).

Handler (Cancer)

The ETU cancer risks for all mixing/loading (M/L) scenarios (all formulation types) for private 

handlers are estimated in the 10-6to 10-8range at label PPE (i.e., gloves, no respirator).

The ETU cancer risks for commercial handlers M/L scenarios using dry flowable (DF) 

formulations in support of aerial applications ranged from 1 x10-5at label specified PPE to 5 x10-

7 with the use of water soluble bags (WSB) as an engineering control measure; the requested 

addition of a PF5 respirator to the DF labels would result in a cancer risk of 3 x10-6for these M/L 

handlers. Cancer risks for commercial M/L scenarios using DF formulations in support of 

airblast applications ranged from 2 x10-6at label PPE to 4 x10-7 with the addition of the PF5 

respirator. 
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Cancer risks for both private and commercial handlers M/L liquids in support of aerial and 

airblast applications are in the 10-7to 10-8range at label PPE. 

For applicators, the ETU cancer risks for applying to walnuts via airblast range from 10-6(open 

cab, no respirator) to 10-8(closed cab). The cancer risks for mixing/loading/application (M/L/A) 

scenarios are estimated in the 10-7range for both private and commercial handlers at label PPE.

Post-Application (Non-Cancer)

All post-application occupational exposure scenarios assessed resulted in short-term/ 

intermediate term dermal MOEs that do not exceed HED's level of concern (i.e., ETU MOEs ≥ 

1000) at mancozeb current Restricted Entry Interval (REI) of 24 hours which is also proposed for 

walnut crops.

Post-Application (Cancer)

The ETU cancer risk estimates for walnut post-application worker scenarios assessed are in the 

10-7to 10-8range for private growers and 10-6to 10-7for commercial growers at Day 1 (at the 24 

hour REI). 

Environmental Justice Considerations

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. Refer to Section 

3.5 of this document.

Review of Human Research

(See Appendix C of this document.)

2.0 HED Recommendations

HED recommends for registration and tolerances for mancozeb uses on walnuts and imported 

tangerines provided the label modifications are made as outlined in Section 2.3 below. The 

specific tolerance recommendations are provided in Section 2.2.2.

2.1 Data Deficiencies

Toxicology data gaps for ETU include a 2-generation reproduction study in rats, a developmental 

neurotoxicity study in rats, and a developmental thyroid toxicity study in rats. These datagaps 

and the mancozeb datagap of a developmental thyroid toxicity study in rats will be satisfied with 

an extended one-generation reproductive toxicity study on ETU, which is currently in progress. 

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method
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The residue of concern for tolerance enforcement is mancozeb measured as CS2. There are 

adequate methods available for the enforcement of crop tolerances with PAM Vol. II listing 

Methods I, II, III, IV, and A for determining dithiocarbamate residues in/on plant commodities. 

The Keppel colorimetric method (Method III) is preferred since this procedure determines 

EBDCs as a group by degradation to CS2. The analytical method for ETU is based on the 

methodology published by Olney and YIP (JAOAC 54:165-169). There are also adequate 

enforcement methods available to perform the determination of residues in animal commodities 

developed by the registrant (DP No. D352531, C. L. Olinger, 07/16/2009). Mancozeb is not 

recovered through any of the FDA Multi-Residue Method testing protocols. 

Analytical standards for mancozeb are currently available in the EPA National Pesticide 

Standards Repository. The current stock of standards expired on 03/20/2013. Analytical 

reference standards of mancozeb must be supplied and supplies replenished as requested by the 

Repository. The reference standards should be sent to the Analytical Chemistry Lab, which is 

located at Fort Meade, to the attention of either Theresa Cole or Thuy Nguyen at the following 

address:

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.)

2.2.2 Recommended Tolerances

Pending revisions of Sections B (see Section 2.3.1 below) and F (see Section 2.2.3) there are no 

deficiencies that preclude establishing permanent tolerances for residues of mancozeb on walnut

and imported tangerines. The tolerance definition should be as follows:

Tolerances are established for residues of mancozeb (a coordination product of zinc ion and 

maneb (manganese ethylenebisdithiocarbamate)), including its metabolites and degradates, in or 

on the commodities in the table below. Compliance with the tolerance levels specified below is 

to be determined by measuring only those mancozeb residues convertible to and expressed as

carbon disulfide, in or on the commodity. 

Table 2.2.2 Tolerance Summary for Mancozeb

Commodity Proposed Tolerance 

(ppm)

Recommended 

Tolerance (ppm)

Comments

Correct Commodity Definition

Walnut 0.75 0.70

Tangerine 10.0 10

2.2.3 Revisions to Petitioned-For Tolerances
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HED is recommending tolerance levels for mancozeb in walnuts that is only slightly different 

than what the petitioner is proposing. The newly submitted walnut data (converted to CS2 

equivalents) were evaluated using by HED using the Organization for Economic Cooperation 

and Development (OECD) tolerance calculation procedures. Based on the result of this 

statistical analysis, a tolerance of 0.70 ppm is recommended for walnuts. A revised Section F 

should be submitted for the walnut petition (PP#1F7935).

2.2.4 International Harmonization

The mancozeb Codex and U.S. residue definitions are similar. Both definitions stipulate that the 

residue of concern is mancozeb, measured as carbon disulfide.

There are no Codex, Canadian or Mexican MRLs established for mancozeb on walnuts. As a 

result, international harmonization is not an issue for the proposed use on walnuts. There is a 

MRL of 10 ppm established by Codex for the use of EBDC compounds on mandarins. Using the 

OECD tolerance calculation procedures, a U.S. tolerance of 8.0 ppm for residues of mancozeb on 

imported tangerines was calculated based on the submitted tangerine field trial data. In order to 

harmonize with the established Codex MRL, a U.S. tolerance of 10 ppm is recommended.

2.3 Label Recommendations

2.3.1 Recommendations from Residue Reviews

The use directions and product labeling specified in Section B (PP#1F7935) should be amended 

to delineate a maximum total seasonal rate for treating walnuts with mancozeb; the instructions 

for the application rate and number of applications should be expanded to specify the “maximum 

allowed” on each product label. In addition, the product labels should specify a re-treatment 

interval of 10 days between applications. 

2.3.2 Recommendations from Occupational Assessment

Non-cancer risks estimates for mixers/loaders scenarios using dry flowable formulations in 

support of aerial applications to walnuts exceed HED’s level of concern at label specified PPE 

(i.e. gloves, no respirator) but are not of concern when respirators are worn. It should be noted 

that no respiratory protection equipment or other engineering control measures are requested on 

the DF labels (EPA Reg.70506-234 and EPA Reg.70506-185 labels). The DF labels should be 

amended to stipulate the use of respirators for mixer/loaders.

2.3.3 Recommendations from Residential Assessment

None.
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3.0 Introduction

3.1 Chemical Identity

Table 3.1 Mancozeb Nomenclature.

Chemical structure

Common name Mancozeb

Company experimental name Not applicable

IUPAC name manganese ethylenebis(dithiocarbamate)(polymeric) complex with zinc salt

CAS name [[1,2-ethanediylbis[carbamodithioato]](2-)]manganese mixture with [[1,2-

ethanediylbis[carbamodithioato]](2-)]zinc

CAS registry number 8018-01-7

End-use product (EP) (Dithane® M45 Fungicide; EPA Reg. No. 62719-387); (Penncozeb 75DF; EPA 

Reg. No. 70506-185); ( Penncozeb 4FL Flowable Fungicide;EPA Reg. No. 

70506-194); ( Manzate Pro-Stick Fungicide;EPA Reg. No. 70506-234); (Manzate 

Flowable; EPA Reg. No. 70506-236). 

Chemical structure of ETU 

metabolite

ethylenethiourea

3.2 Physical/Chemical Characteristics

Mancozeb is a coordination product of zinc ion and maneb (manganese ethylenebisdithiocarbamate), which contains 20% manganese and 2.5% zinc. Technical mancozeb is a 

yellowish powder with a negligible vapor pressure at 20 °C. Mancozeb is practically insoluble 

in water, and most organic solvents. Mancozeb decomposes in acid and alkaline conditions, with 

heat, and upon exposure to moisture and air. Mancozeb is short lived in soil and water and 

would therefore not be expected to remain in surface water long enough to reach a location that 

would supply water for human consumption. However, mancozeb’s degradate ETU is highly 

water soluble, highly vulnerable to indirect photolysis, and is moderately mobile. ETU has an 

aerobic soil half-life of 3 days, and an estimated aquatic aerobic metabolism half-life of six days. 

The measured anaerobic aquatic metabolism half life is 149 days. ETU has a relatively high 

vapor pressure, but the high solubility reduces the possibility of losses from surface water due to 

volatilization. See Appendix B for a table of physicochemical properties of mancozeb.

3.3 Pesticide Use Pattern

N

H

S

S

N

H

S

Mn

S

Zn

x

y

HN NH

S
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There are four (4) United Phosphorus mancozeb end-use products relevant to the petition for 

treating walnuts (PP#1F7935). These products are Penncozeb 75DF (EPA Reg. No. 70506-185), 

Penncozeb 4FL Flowable Fungicide (EPA Reg. No. 70506-194), Manzate Pro-Stick Fungicide 

(EPA Reg. No. 70506-234), and Manzate Flowable (EPA Reg. No. 70506-236). The proposed 

patterns of use for both formulations of mancozeb for treating walnuts are summarized below in 

Table 3.3.1. Refer to Section 2.3 for recommended modifications to the proposed labels.

The Dow mancozeb product proposed for treating tangerines in Korea (PP#2E806) is the 

Dithane® M45 Fungicide (EPA Reg. No. 62719-387) which is a 75% wettable powder (WP) 

formulation. A copy of the Korean mancozeb label translated into English was provided by Dow 

for assessment. The proposed pattern of use for this mancozeb product used for treating 

tangerines in Korea is summarized below in Table 3.3.2.

Table 3.3.1 Summary of Directions for the Use of Mancozeb on Walnuts.

Crop Applic. 

Timing, Type, 

and Equip.

Product Applic. 

Rate

(lb ai/A)

Max. No. 

Applic. per 

Season

Max. Seasonal 

Applic. Rate

(lb ai/A)

PHI

(days)

Use Directions and Limitations

Walnuts Broadcast 

foliar spray

Penncozeb Technical

Manzate Pro-Stick

Penncozeb 75DF

(water dispersible 

granule products)

1.8 10 18.0 75

RTI: 10 days

Apply by ground in a minimum of 

100 gal water/A, or by air in a 

minimum of 10 gal water/A.

Do not apply through any 

irrigation system.

Begin applications at early prebloom prior to or when catkins are 

partially expanded. Make 

additional applications during 

bloom and early nutlet stage, or as 

needed if frequent rainfall occurs.

Restrictions: This product must be 

tank mixed with a fixed copper 

product (Cuprofix Ultra 40 

Disperss) which is registered for 

use on Walnuts.

Manzate FL

Penncozeb 4FL

(liquid flowable 

products)
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Table 3.3.2 Summary of Directions for the Use of Mancozeb on Tangerines

Crop Applic. Timing, 

Type, and Equip.

Product Max. Applic. 

Rate

(lb ai/A)

[kg ai/ha]

Max. No. 

Applic. 

per 

Season

Max. Seasonal 

Applic. Rate

(lb ai/A)

[kg ai/ha]

PHI

(days)

Use Directions and Limitations

Tangerines

Korea:

Postemergence; 

ground 

equipment 

(boom sprayer)

Dithane 

M-45

(75% WP)

6.7

[7.5] 4

26.8

[30]

21

Applications to be made from 

fruit set (early June) until fruit 

growth is completed 

(September); spray volume is 

3,000-5,000 L/ha [321-535 

gal/A], depending on tree size, 

with a concentration of 0.15 kg 

ai/hL [0.013 lb ai/gal]; may be 

mixed with insecticides. A 

retreatment interval of 10 days 

is specified

3.4 Anticipated Exposure Pathways

Mancozeb is registered for use on numerous agricultural crops as well as on golf courses and in 

home vegetable gardens. Exposure to mancozeb, and its degradate ETU, may occur from 

ingestion of residues in/on foods and in drinking water, and via the dermal and inhalation routes 

for adults using mancozeb products in occupational and residential settings. In addition, both 

youth and adults may be exposed dermally to mancozeb and ETU in post-application scenarios 

involving the use of mancozeb on golf courses and in home gardens. There is also a potential for 

post-application exposure for workers re-entering treated fields. 

Risk assessments have been previously conducted for mancozeb; however, since the previous 

assessments toxicity points of departure and uncertainty factors have been revised. This risk 

assessment considers the all of the aforementioned exposure pathways based on the proposed 

new uses of mancozeb, as well as the existing uses.

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.eh.doe.gov/oepa/guidance/justice/eo12898.pdf. As a part of every pesticide risk 

assessment, OPP considers a large variety of consumer subgroups according to well-established 

procedures. In line with OPP policy, HED estimates risks to population subgroups from 

pesticide exposures that are based on patterns of that subgroup’s food and water consumption, 

and activities in and around the home that involve pesticide use in a residential setting. 

Extensive data on food consumption patterns are compiled by the USDA under the Continuing 

Survey of Food Intake by Individuals (CSFII) and are used in pesticide risk assessments for all 

registered food uses of a pesticide. These data are analyzed and categorized by subgroups based 

on age, season of the year, ethnic group, and region of the country. Additionally, OPP is able to 

assess dietary exposure to smaller, specialized subgroups and exposure assessments are 
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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 postapplication 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

Mancozeb is a fungicide in the class of ethylenebis dithiocarbamates (EBDC), which also 

includes maneb and metiram; all of these compounds have a common metabolite/degradate, 

ethylenethiourea (ETU). Some of the more notable toxicity in the mancozeb studies was due to 

toxicity from the metabolite, ETU. As described in more detail below, thyroid toxicity and 

developmental toxicity in rats were both due to toxicity from ETU. Injury to peripheral nerves 

occurred in mancozeb toxicity studies but not in studies with ETU. Because of the overlap of 

toxicity profiles, this hazard characterization includes some information on ETU. More details 

about the hazard profile for ETU are in a forthcoming separate ETU risk assessment. 

Since the last comprehensive mancozeb/ETU risk assessment (6/11/07, D327307 & D327318), 

the interspecies uncertainty factor is reduced from 10X to 3X because of toxicodynamic 

differences in adult thyroid function that result in greater sensitivity of the adult rat to 

hypothyroidism compared to adult humans. The 3X toxicodynamics part of the 10X interspecies 

factor is removed in those assessments that are based on rat thyroid toxicity endpoints, leaving 

the 3X portion for toxicokinetic interspecies differences (Hazard Science Policy guidance). 

Additionally, a 10X FQPA UFDB was applied previously to all assessments due to the datagaps 

for a 2-generation reproduction study in rats, a rat developmental neurotoxicity study, and a rat 

developmental thyroid toxicity study for ETU. Because these datagaps could affect women of 

childbearing age or the developing young, the FQPA SF is retained for females 13-49 years of 

age and for children less than 6 years of age. The FQPA SF is reduced to 1X for all other 

population groups, including children greater than 6 years who have a thyroid system similar to 

adults, because endpoints from the extended one generation study will not affect those 

population groups (children > 6 years, females > 49 years, and adult males). 

4.1 Summary of Toxicological Effects

The database for mancozeb is extensive. There are acceptable subchronic oral studies in rats, 

mice, and dogs; a dermal toxicity study in rabbits; an inhalation toxicity study in rats; chronic 

toxicity studies in rats and dogs; carcinogenicity studies in rats and mice; acute neurotoxicity, 

subchronic neurotoxicity, and developmental neurotoxicity studies in rats; developmental 

toxicity studies in rats and rabbits and a 2-generation reproduction study in rats; a battery of 

mutagenicity studies; an immunotoxicity study in rats; and metabolism studies. Although most 

of the mancozeb risk assessment endpoints are of thyroid toxicity, a developmental thyroid 

toxicity study is not available. This datagap will be satisfied by an ongoing developmental 
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thyroid study with ETU, which is part of an extended one-generation reproductive toxicity study 

on ETU, described below. 

The toxicology database on ETU is sufficient for assessing the toxicity and characterizing the 

hazard of ETU. There are acceptable subchronic oral studies in rats and dogs, several rat 

developmental toxicity studies from the open literature, a rabbit developmental toxicity study, an 

immunotoxicity study in rats, and a dermal absorption study in rats. Data gaps for ETU include a 

2-generation reproduction study in rats, a developmental neurotoxicity study in rats, and a 

developmental thyroid toxicity study in rats. These datagaps will be satisfied with an extended 

one-generation reproductive toxicity study on ETU, which is in progress. 

Thyroid toxicity in rat and dog studies with mancozeb was manifested as decreased thyroxine, 

increased thyroid weight, and microscopic thyroid lesions (mainly thyroid follicular cell 

hyperplasia), accompanied by increased thyroid stimulating hormone. These effects were due to 

inhibition of thyroid peroxidase by the metabolite, ETU. 

Fetal malformations in the rat developmental mancozeb study occurred throughout the body, at a 

dose that was lethal to dams. Malformations in the head included hydrocephaly (increased 

cerebrospinal fluid in brain ventricles) and related lesions which included brain atrophy and 

edema, compressions and hemorrhages of the spinal cord, deficiency of tissue in the olfactory 

bulb, decreased ossification of the skull, and meningoencephalocele (meninges of the brain 

protruding through the skull). Defects throughout the skeletal system included curved clavicle, 

fused sternebrae, absent caudal or sacral vertebrae, fused and/or thickened ribs, wavy ribs, 

misshapen or incomplete ossification of hindlimb long bones, kyphosis, incomplete ossification 

or misshapen pelvis. Gross defects included agnathia (small or absent lower jaw), cleft palate, 

cleft lip, club limb, stubby tail, forelimb flexure, kinked tail, and cryptorchidism. The 

developmental malformations in the mancozeb developmental toxicity study did not indicate 

increased sensitivity of fetuses relative to adults, because they were observed only at the dose 

that was lethal to the dams. It is to be noted that there were many ETU developmental studies 

with tight dose spacing, which was necessary because of the steep dose-response for 

hydrocephaly. Several ETU studies clearly showed hydrocepahly in the absence of maternal 

toxicity. There is only one mancozeb developmental study. This study had wide dose spacing 

and the developmental toxicity occurred at a dose that was lethal to dams. If there had been 

intermediate doses, it is concluded that hydrocephaly likely would have been seen in the absence 

of maternal toxicity. However, there was evidence of sensitivity in the developmental 

neurotoxicity study with mancozeb because decreased pup body weight occurred in the absence 

of maternal toxicity. 

The developmental toxicity with mancozeb is attributed to ETU and the many literature studies 

with ETU help characterize the developmental hazard with mancozeb. The ETU studies showed 

a steep dose-response for developmental toxicity and found that hydrocephaly occurred after 

treatment with a single dose of ETU in the absence of maternal toxicity. The malformations 

occurred in rats, but generally not in other species, although hydrocephaly and domed head were 

observed in a rabbit developmental study with ETU. 

In the mancozeb rabbit developmental study, abortions occurred at the same dose as did maternal 
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mortality. In a 2-generation reproduction study with mancozeb, there were no adverse 

reproductive or offspring effects; parental toxicity included body weight decrements and thyroid 

toxicity. 

Microscopic injury to peripheral nerves was seen in the rat subchronic neuropathology study, and 

at higher doses was accompanied by clinical signs (abnormal gait and limited use of rear legs) 

and loss of muscle mass. Females were more sensitive than males regarding clinical signs. 

Decreased motor activity occurred in the acute neurotoxicity study. In the developmental 

neurotoxicity study, there was no maternal toxicity and pup effects were limited to decreased 

body weight. 

Other toxicity with mancozeb included increases in bilateral retinopathy in the chronic rat study. 

Elevated cholesterol and a mild, regenerative, anemia occurred in subchronic and chronic dog 

studies. Mancozeb is not acutely toxic with regard to lethality via the oral, dermal, or inhalation 

routes of exposure (Tox Category IV). Mancozeb is not a skin irritant (Tox Category IV) nor is 

it a skin sensitizer although it did cause eye irritation (Tox Category III).

Thyroid follicular cell adenomas and carcinomas were increased in high-dose males and females 

in the combined rat toxicity/carcinogenicity study with mancozeb. Doses in a mouse study were 

too low to assess carcinogenicity, and there were no treatment-related changes in tumor rates. 

Mancozeb’s potential for carcinogenicity (as well as that of the other EBDCs) is assessed by the 

metabolite, ETU, which is classified as a probable human carcinogen (B2), with a cancer 

potency factor (Q1

*

) of 0.0601 (mg/kg/day)-1for risk assessment. On this basis, mancozeb 

cancer risk has been calculated by estimating exposure to mancozeb-derived ETU (including the 

metabolic conversion) and using the ETU cancer potency factor to provide a quantitative 

estimate of risk. 

A developmental thyroid study with mancozeb is not available. Instead, the thyroid toxicity of 

mancozeb in offspring is being evaluated in an extended one-generation reproductive toxicity 

study with ETU, which will also evaluate thyroid effects in the fetus and offspring. This study is 

presently being conducted. An immunotoxicity study with mancozeb and one with ETU have 

been submitted and reviewed. These studies did not show any concerns for immunotoxicity. 

In the rat metabolism study, mancozeb was rapidly absorbed after oral administration with 

highest accumulation of radioactivity in the thyroid due to ETU residues; no parent compound 

was detected in the thyroid. There was no indication of significant overall accumulation of 

mancozeb and metabolites in the body. The majority of mancozeb was metabolized to ETU and 

excreted in the urine. Radioactivity was rapidly absorbed into plasma with t1/2 absorption times 

of 0.7 to 1.0 hour for the 1.5 mg/kg group and 1.7 hours for the 100 mg/kg group. Peak plasma 

concentrations were reached within 3 hours for the 1.5 mg/kg group and 6 hours for the 100 

mg/kg group. The t1/2 for the rapid phase of elimination was approximately 4-6 hours for both 

dose groups. The t1/2 for the slow phase of elimination was 36.5 hours in the 1.5 mg/kg group 

and 25 hours in the 100 mg/kg group. 
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Mancozeb concentrated in the liver and thyroids in comparison to whole blood concentrations. 

Peak liver concentrations of radioactivity were reached within 6 hours and were approximately 

1.7x higher than whole blood concentrations after 1.5 mg/kg dosing and were approximately 6x 

higher than whole blood after 100 mg/kg dosing. The thyroids had the highest mean residue 

concentration of any tissue, although individual thyroid concentrations varied as much as 30x 

within a group. Peak thyroid concentrations were reached within 6 hours after treatment with 1.5 

mg/kg or within 24 hours after treatment with 100 mg/kg mancozeb. Peak thyroid 

concentrations of radioactivity were 42-45x higher than in whole blood after treatment with 1.5 

mg/kg and were 6-16x higher than in whole blood after treatment with 100 mg/kg. The 

radioactivity levels in the thyroids decreased between 24 and 48 hours and then increased 

between 48 and 96 hours. Although radioactivity levels in the thyroids had increased after 48 

hours, there was no indication of significant overall accumulation of mancozeb and metabolites 

in the body. Average radioactivity residue levels in tissues 96 hours post-dosing were < 4% of 

the dose. The area under the plasma concentration-time curve (AUC) for ETU in males was 

6.4% of the AUC for plasma radioactivity after dosing with 100 mg/kg radiolabeled mancozeb; 

the AUC for ETU in females was 3.1% of the AUC for plasma radioactivity. ETU had a plasma 

t1/2 of 3.9 hours in males and 4.7 hours in females. 

In oral rat metabolism studies with radiolabelled mancozeb and other EBDCs, approximately 

20% of EBDC was converted to ETU on a molar basis, which equated to 7.5% conversion on a 

weight basis (Albin Kocialski memo, 9/12/89). While this metabolic conversion has been 

included in the mancozeb and ETU risk assessment for all routes of exposure, there is some

uncertainty in assuming the metabolic conversion occurs following dermal and inhalation dosing 

because absorption after dermal and inhalation dosing initially bypasses the liver. 

The mancozeb dermal absorption factor is 1%, based on two non-guideline dermal absorption 

studies, which together satisfy the guideline requirement for a dermal absorption study on 

mancozeb. This value is supported by comparison of NOAEL values between the 28-day dermal 

toxicity study in rats and the 13-week rat feeding study (1000 mg/kg/day 9.25 mg/kg/day = 

0.9% dermal absorption). The dermal absorption factor of 1% was also consistent with dermal 

absorption factors for the other EBDCs. 

The ETU dermal absorption factor is 26%, based on a dermal absorption study in rats. This 

value was determined at the lowest dermal dose after 10 hours of exposure followed by washing 

of the skin. ETU residues were highest in the thyroid.

4.2 Safety Factor for Infants and Children (FQPA Safety Factor)

For mancozeb, the FQPA SF (safety factor) of 10X is retained for women of childbearing age 

and for children less than 6 years old because of an inadequate database for the developing 

thyroid. Brain development is very sensitive to perturbations in thyroid hormones and it is 

possible that the developmental thyroid study (being conducted with ETU) will result in lower 

NOAELs for these populations than are presently being used to assess risk. 

Results from the developmental thyroid study will not affect endpoints for children over 6 years 

of age (for whom the thyroid system is more developed) or adults as thyroid data for those 
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populations are already available. The database for toxicity studies affecting these populations is 

complete. Therefore, the FQPA safety factor is reduced to 1X for these populations. 

For ETU, the datagaps being addressed in the extended one-generation reproductive toxicity 

study could affect women of childbearing age or the developing young, and the FQPA SF of 10X 

is retained for females 13-49 years of age and for children less than 6 years of age. The FQPA 

SF is reduced to 1X for all other population groups, including children greater than 6 years who 

have a thyroid system similar to adults, because endpoints from the extended one generation 

study will not affect those population groups (children > 6 years, females > 49 years, and adult 

males). Although there was fetal sensitivity for malformations in the ETU developmental rat 

studies, the endpoints that were selected are protective of these effects. 

4.2.1 Completeness of the Toxicology Database

The toxicology database for mancozeb and ETU is sufficient for assessing the toxicity and 

characterizing the hazard of these chemicals. There are guideline studies for developmental 

toxicity in rats and rabbits, reproductive toxicity in rats, acute neurotoxicity, subchronic 

neurotoxicity, immunotoxicity, and developmental neurotoxicity in rats for mancozeb. Thyroid 

toxicity in young rats is being evaluated as part of an extended one-generation reproductive 

toxicity study with ETU. The database for ETU is incomplete, but the extended one-generation 

reproductive toxicity study on ETU will satisfy these datagaps. An immunotoxicity study on 

ETU is available.

4.2.2 Evidence of Neurotoxicity

Injury to peripheral nerves (demyelination, myelin phagocytosis, Schwann cell proliferation, 

thickened myelin sheath, intrasheath ellipsoids, neurofibrillary degeneration, and myelin ovoids, 

bubbles, and debris) was seen microscopically in the rat subchronic neurotoxicity study with 

associated clinical signs (abnormal gait and limited use of rear legs) and loss of muscle mass. 

Decreased motor activity was noted in an acute neurotoxicity study in rats with mancozeb. No 

neurotoxicity occurred in the mancozeb developmental neurotoxicity study in rats. 

Neurotoxicity was not noted in toxicity studies with ETU, but the toxicity profile for ETU shows 

that the principal toxic effects occur in the thyroid. The endpoints that were selected are based on 

thyroid effects and would be protective of any potential neurotoxicity following ETU exposure.

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

Developmental malformations in the mancozeb rat developmental toxicity study did not indicate 

sensitivity of offspring because they occurred at the same dose that caused maternal mortality. 

There was no indication of enhanced susceptibility of offspring in the mancozeb rabbit 

developmental study because abortions occurred at the same dose that also caused maternal 

mortality. There was no evidence of sensitivity in the 2-generation reproduction study with 

mancozeb in rats. As noted above, the mancozeb developmental toxicity study had wide dose 

spacing and developmental toxicity occurred at a dose that was lethal to dams. If there had been 
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intermediate doses, it is concluded that hydrocephaly likely would have been seen in the absence 

of maternal toxicity. However, evidence of sensitivity was noted in the developmental 

neurotoxicity study with mancozeb, since decreased pup body weight occurred in the absence of 

maternal toxicity. 

There is evidence of increased susceptibility following in utero exposure to ETU in the rat 

developmental toxicity studies. Several developmental toxicity studies with ETU in the open 

literature demonstrate quantitative and qualitative fetal sensitivity. In one study, developmental 

toxicity [brain malformations (exencephaly, dilated ventricles, and hypoplastic cerebellum)] was 

observed at a dose level considerably lower than the dose causing maternal toxicity (mortality). 

In another study, developmental toxicity (dilated ventricle of the brain) was seen in the absence 

of maternal toxicity. Additionally, developmental effects (dilated ventricles of the brain, 

hydroureter, short/kinky tail, and dilated ureters) were seen in another study at a dose that only 

induced decreases in body weight gain in the dams. 

4.2.4 Residual Uncertainty in the Exposure Database

HED has used refined assumptions in the food portion of the dietary exposure assessment, 

including the use of percent crop treated estimates and monitoring residue values for several

commodities including some major contributors to the dietary risk such as milk and corn 

commodities. Modeling and monitoring data were used to derive estimated drinking water 

concentrations. The residential exposure assessment was conducted such that residential 

exposure and risk will not be underestimated. The aggregate exposure and risk estimates 

presented in this assessment are not expected to underestimate actual exposure and risk expected 

based on the current and proposed use patterns.

The database for mancozeb is extensive and is sufficient for characterizing toxicity and hazard. 

Although most of the mancozeb risk assessment endpoints are of thyroid toxicity, a 

developmental thyroid toxicity study is not available. This datagap will be satisfied by an 

ongoing developmental thyroid toxicity study with ETU, which is part of an extended onegeneration reproductive toxicity (EOGRT) study on ETU. For mancozeb, the FQPA SF (safety 

factor) of 10X is retained for women of childbearing age and for children less than 6 years old 

because of an inadequate database for the developing thyroid. Brain development is very 

sensitive to perturbations in thyroid hormones and it is possible that the developmental thyroid 

toxicity study (being conducted with ETU) will result in lower NOAELs for these populations 

than are presently being used to assess risk. The FQPA safety factor for mancozeb is reduced to 

1X for other lifestages (children > 6 years, females > 49 years, and adult males), for which the 

thyroid is largely developed and there are applicable thyroid data.

Toxicology data gaps for ETU include a 2-generation reproductive toxicity study in rats, a 

developmental neurotoxicity study in rats, and a developmental thyroid toxicity study in rats. 

These datagaps will be satisfied with the ongoing EOGRT study on ETU. The datagaps being 

addressed in the EOGRT study could affect women of childbearing age or the developing young, 

and the FQPA SF of 10X is retained for females 13-49 years of age and for children less than 6 

years of age. The FQPA safety factor for ETU is reduced to 1X for other lifestages. Although 

there was fetal sensitivity for malformations in the ETU developmental rat studies, the endpoints 
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that were selected are protective of these effects. 

4.3 Toxicity Endpoint and Point of Departure Selections

A detailed description of the toxicity studies used for selecting toxicity endpoints and points of 

departure for various exposure scenarios is presented in Appendix A. The doses and endpoints 

are summarized below and in Tables 4.3.1 through 4.3.4 which also provide the appropriate 

safety factors.

Mancozeb

Acute dietary, females 13-49 years of age: The acute dietary endpoint for females 13-49 years 

old was selected from a developmental toxicity study in rats. The LOAEL was 512 mg/kg/day, 

based on hydrocephaly and other malformations. The NOAEL was 128 mg/kg/day. This 

endpoint is appropriate because hydrocephaly occurred after a single dose of ETU. 

Acute dietary, general population: The acute dietary endpoint for the general population was 

selected from an acute neurotoxicity study in rats. The LOAEL was 1000 mg/kg/day, based on 

decreased motor activity. The NOAEL was 500 mg/kg/day. 

Chronic dietary: The chronic reference dose was selected from a chronic toxicity study in rats. 

The LOAEL was 30.9 mg/kg/day, based on thyroid toxicity (decreased thyroid hormones, 

microscopic thyroid changes, and increased thyroid weight). The NOAEL was 4.83 mg/kg/day. 

Incidental oral exposure, children <6 years: The incidental oral endpoint for children less than 6 

years of age was selected from a subchronic feeding study in rats. The LOAEL was 17.82 

mg/kg/day, based on decreased thyroid hormone. The NOAEL was 9.24 mg/kg/day. 

Dermal exposure, short- and intermediate-term: Risk assessment will not be quantified because 

no systemic toxicity was noted in a dermal toxicity study in rats at the limit dose. There are no 

developmental or reproductive concerns at doses that would occur from dermal exposure from 

registered uses considering the dermal absorption factor of 1%. 

Dermal exposure, long-term: The long-term dermal endpoint was selected from a chronic oral 

toxicity study in rats. The LOAEL was 30.9 mg/kg/day, based on thyroid toxicity (decreased 

thyroid hormones, microscopic thyroid changes, and increased thyroid weight). The NOAEL was 

4.83 mg/kg/day. 

Inhalation exposure: The inhalation endpoint was selected from a subchronic inhalation study in 

rats. The LOAEL was 0.326 mg/L, based on thyroid toxicity (thyroid hyperplasia and decreased 

thyroxine). The NOAEL was 0.079 mg/L.

ETU

Acute dietary, females 13-49 years: The ETU acute dietary endpoint for females 13-49 years old 

was selected from a non-guideline developmental toxicity study in rats. The LOAEL was 10 

mg/kg/day, based on developmental malformations of the brain, including exencephaly, dilated 

ventricles and hypoplastic cerebellum. The NOAEL was 5 mg/kg/day. 
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Acute dietary, general population, including infant and children: No hazard or appropriate acute 

endpoint attributable to a single exposure was identified from the available oral toxicity 

database; therefore, no acute dietary risk is expected following acute exposure to ETU. 

Chronic dietary, all populations: The ETU chronic reference dose was selected from a chronic 

oral toxicity study in dogs. The study NOAEL was 0.18 mg/kg/day, based on decreased body 

weight gain, increased thyroid weight, and microscopic changes in the thyroid observed at the 

LOAEL of 1.99 mg/kg/day. 

Short-term oral, children <6 years: The incidental oral endpoint for children less than 6 years of 

age was selected from a non-guideline 4-week range-finding oral toxicity study conducted in 

dogs. The NOAEL was 7 mg/kg/day, based on gross thyroid lesions and decreased thyroid 

hormone levels at the LOAEL of 34 mg/kg/day. The endpoint is supported by a subchronic oral

toxicity study in dogs in which the NOAEL for thyroid effects was similar (6 mg/kg/day).

Short and intermediate-term dermal, all populations other than females 13-49 years: In the 

absence of a dermal toxicity study for ETU, the non-guideline 4-week range-finding toxicity 

study conducted in dogs was used to select short- and intermediate-term dermal endpoints for all 

population groups other than females 13-49 years of age. The NOAEL was 7 mg/kg/day based 

on gross thyroid lesions and decreased thyroid hormone levels at the LOAEL of 34 mg/kg/day. 

Because an oral toxicity study was chosen, the 26% dermal absorption factor for ETU should be 

used in the dermal exposure assessment. 

Short and intermediate-term dermal, females 13-49 years: In the absence of a dermal toxicity 

study for ETU, the non-guideline oral developmental study in rats was used to select an endpoint 

for short- and intermediate-term dermal risk assessments for females 13-49 years of age. The 

study NOAEL was 5 mg/kg/day, based on developmental malformations of the brain, including 

exencephaly, dilated ventricles, and hypoplastic cerebellum, observed at the LOAEL of 10 

mg/kg/day. Because an oral toxicity study was chosen, the 26% dermal absorption factor for 

ETU should be used in the dermal exposure assessment. 

Long-term dermal, all populations: The long-term dermal endpoint for all populations is selected 

from the chronic toxicity study in dogs. The NOAEL is 0.18 mg/kg/day based on decreased 

body weight gain, increased thyroid weight, and microscopic changes in the thyroid at the 

LOAEL of 1.99 mg/kg/day. Since an oral study was selected, estimated dermal exposure should 

be adjusted by 26%, the ETU dermal absorption factor. 

Short and intermediate-term inhalation, all populations other than females 13-49 years: In the 

absence of an inhalation toxicity study for ETU, the non-guideline 4-week range-finding toxicity 

study conducted in dogs was used to select short- and intermediate-term inhalation endpoints for 

all population groups other than females 13-49 years of age. The NOAEL was 7 mg/kg/day 

based on gross thyroid lesions and decreased thyroid hormone levels at the LOAEL of 34 

mg/kg/day. Because an oral toxicity study was chosen, it will be assumed that inhalation 

absorption is equivalent to oral absorption. 
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Short and intermediate-term inhalation, females 13-49 years: In the absence of an inhalation

toxicity study for ETU, the non-guideline oral study in rats was used to select an endpoint for 

short- and intermediate-term inhalation risk assessments for females 13-49 years of age. The 

study NOAEL was 5 mg/kg/day based on developmental malformations of the brain, including 

exencephaly, dilated ventricles, and hypoplastic cerebellum, observed at the LOAEL of 10 

mg/kg/day. Because an oral toxicity study was chosen, it will be assumed that inhalation 

absorption is equivalent to oral absorption. 

Long-term inhalation, all populations: The long-term inhalation endpoint for all populations is 

selected from the chronic toxicity study in dogs. The NOAEL is 0.18 mg/kg/day based on 

decreased body weight gain, increased thyroid weight, and microscopic changes in the thyroid at 

the LOAEL of 1.99 mg/kg/day. Because an oral toxicity study was chosen, it will be assumed 

that inhalation absorption is equivalent to oral absorption. 

Cancer

Thyroid follicular cell adenomas and carcinomas were increased in high-dose males and females 

in the combined rat toxicity/carcinogenicity study with mancozeb. Doses in a mouse study were 

too low to assess carcinogenicity, and there were no treatment-related changes in tumor rates. 

Mancozeb’s potential for carcinogenicity is assessed based on the metabolite, ETU, which is 

classified as Group B2, with a cancer potency factor [Q1*, 0.0601 (mg/kg/day)-1] for risk 

assessment. Because mancozeb is known to be converted to ETU, it has also been classified as 

Group B2 for carcinogenicity, and after applying the metabolic conversion factor for EBDC to 

ETU (0.075), the ETU cancer potency factor is used for assessing cancer risk associated with 

mancozeb uses.

Table 4.3.1 Summary of Toxicological Doses and Endpoints for MANCOZEB for Use in Dietary and NonOccupational Human Health Risk Assessments 

Exposure PoD Safety Factors RfD, PAD, LoC Study and Toxicity

Mancozeb Acute Dietary Exposure

Acute Dietary

(Adult Males, 

Females >49, and 

Children ≥ 6 

years)

NOAEL = 

500 

mg/kg/day

UFA= 10x

UFH = 10x

FQPA SF = 1x 

Acute RfD = 5 

mg/kg/day

Acute PAD = 5 

mg/kg/day

Acute neurotoxicity study in the rat 

LOAEL 1000 mg/kg/day based on 

decreased motor activity

Acute Dietary 

(Children < 6 

years)

NOAEL = 

500 

mg/kg/day

UFA= 10x

UFH = 10x

FQPA UFDB = 

10x 

Acute RfD = 

5 mg/kg/day

Acute PAD = 0.5 

mg/kg/day

Acute neurotoxicity study in the rat

LOAEL 1000 mg/kg/day based on 

decreased motor activity

Acute Dietary

(Females 13 – 49 

years)

NOAEL = 

128 

mg/kg/day

UFA= 10x

UFH = 10x

FQPA UFDB = 

10x

Acute RfD = 1.3 

mg/kg/day

Acute PAD = 0.13 

mg/kg/day

Developmental toxicity study in the 

rat

LOAEL = 512 mg/kg/day based on 

hydrocephaly and other 

malformations

Mancozeb Chronic Dietary Exposure
Mancozeb Human Health Risk Assessment DP Nos. 411742 and 411764

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Table 4.3.1 Summary of Toxicological Doses and Endpoints for MANCOZEB for Use in Dietary and NonOccupational Human Health Risk Assessments 

Exposure PoD Safety Factors RfD, PAD, LoC Study and Toxicity

Chronic Dietary 

(Adult Males, 

Females >49, and 

Children ≥ 6 

years)

NOAEL = 

4.83 

mg/kg/day

UFA= 3x

UFH = 10x

FQPA SF = 1x 

Chronic RfD = 0.16 

mg/kg/day

Chronic PAD = 0.16 

mg/kg/day

Toxicity/Carcinogenicity in the rat

LOAEL = 30.9 mg/kg/day based on 

thyroid toxicity

Chronic Dietary 

(Females 13-49 

years and 

Children < 6 

years)

NOAEL = 

4.83 

mg/kg/day

UFA= 3x

UFH = 10x

FQPA UFDB = 

10x 

Chronic RfD = 0.16 

mg/kg/day

Chronic PAD = 0.016 

mg/kg/day

Toxicity/Carcinogenicity in the rat

LOAEL = 30.9 mg/kg/day based on 

thyroid toxicity

Mancozeb Incidental Oral Exposure

Short-term Oral 

(Children < 6 

years of age)

NOAEL = 

9.24 

mg/kg/day

UFA= 3x

UFH = 10x

FQPA UFDB = 

10x

LOC = 300 Subchronic Oral Toxicity Study in 

the rat. LOAEL = 17.82 mg/kg/day 

based on decreased thyroxine

Mancozeb Residential Dermal Exposure

Dermal (Short-, 

and IntermediateTerm, all pop. 

subgroups)

Risk Assessment not required. No systemic toxicity via the dermal route at 1000 mg/kg/day and there 

are no developmental or reproductive concerns at systemic doses which would occur as a result of 

dermal exposures from registered uses (dermal absorption = 1%)

Dermal (LongTerm) (Adult 

Males, Females 

>49 years, 

Children ≥ 6 

years)

NOAEL = 

4.83 

mg/kg/day

DA = 1%

UFA= 3x

UFH = 10x

FQPA SF = 1x

LOC = 30 Toxicity/Carcinogenicity in the rat. 

LOAEL = 30.9 mg/kg/day based on 

thyroid toxicity

Dermal (LongTerm) (Females 

13-49 years and 

Children < 6 

years)

NOAEL = 

4.83

mg/kg/day

DA = 1%

UFA= 3x

UFH = 10x

FQPA UFDB = 

10x

LOC = 300 Toxicity/Carcinogenicity in the rat. 

LOAEL = 30.9 mg/kg/day based on 

thyroid toxicity

Mancozeb Residential Inhalation Exposure (all durations)

Inhalation 

(Adult Males, 

Females >49 

years, and 

Children ≥ 6 

years)

NOAEL = 

0.079 mg/L 

(21 

mg/kg/day)

UFA= 3x

UFH = 10x

FQPA SF = 1x

LOC = 30 Subchronic Inhalation in the rat

LOAEL = 0.326 mg/L based on 

thyroid toxicity

Inhalation 

(Females 13-49 

years and 

Children < 6 

years)

NOAEL = 

0.079 mg/L 

(21

mg/kg/day)

UFA= 3x

UFH = 10x

FQPA UFDB = 

10x

LOC = 300 Subchronic Inhalation in the rat

LOAEL = 0.326 mg/L based on 

thyroid toxicity

Mancozeb Cancer

Cancer (all routes) Mancozeb’s potential for carcinogenicity is due to the formation of the metabolite, ETU, which is 

classified as a probable human carcinogen (B2). Mancozeb’s cancer risk is calculated by estimating 

exposure to mancozeb-derived ETU and using the ETU cancer potency factor (Q1

*

) of 6.01 x 10 -2

(mg/kg/day)-1to quantitate risk.

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). UFL = use of a LOAEL to extrapolate a NOAEL. UFS = use of a short-term study for long-term risk 
Mancozeb Human Health Risk Assessment DP Nos. 411742 and 411764

Page 25 of 77

assessment. UFDB = to account for the absence of key data (i.e., lack of a critical study). FQPA SF = FQPA Safety Factor. PAD 

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

N/A = not applicable. 

Table 4.3.2 Summary of Toxicological Doses and Endpoints for MANCOZEB for Use in Occupational 

Human Health Risk Assessments 

Exposure PoD Safety Factors RfD, PAD, LoC Study and Toxicity

Mancozeb Occupational Dermal Exposure

Dermal (Short-, and 

Intermediate-Term, 

all pop. subgroups)

Risk Assessment not required. No systemic toxicity via the dermal route at 1000 mg/kg/day and there 

are no developmental or reproductive concerns at systemic doses which would occur as a result of 

dermal exposures from registered uses 

Dermal (Long-Term)

(Adult Males, 

Females >49 years)

NOAEL = 4.83 

mg/kg/day

DA = 1%

UFA= 3x

UFH = 10x

LOC = 30 Toxicity/Carcinogenicity in the 

rat. LOAEL = 30.9 mg/kg/day 

based on thyroid toxicity

Dermal (Long-Term)

(Females 13-49 

years)

NOAEL = 4.83 

mg/kg/day

DA = 1%

UFA= 3x

UFH = 10x

UFDB = 10x

LOC = 300 Toxicity/Carcinogenicity in the 

rat. LOAEL = 30.9 mg/kg/day 

based on thyroid toxicity

Mancozeb Occupational Inhalation Exposure (all durations)

Inhalation 

(Adult Males, 

Females >49 years)

NOAEL = 0.079 

mg/L 

[21 mg/kg/day]

UFA= 3x

UFH = 10x

LOC = 30 Subchronic Inhalation in the rat

LOAEL = 0.326 mg/L based on 

thyroid toxicity

Inhalation 

(Females 13-49 

years)

NOAEL = 0.079 

mg/L [21 

mg/kg/day]

UFA= 3x

UFH = 10x

UFDB = 10x

LOC = 300 Subchronic Inhalation in the rat

LOAEL = 0.326 mg/L based on 

thyroid toxicity

Mancozeb Cancer

Cancer (all routes) Mancozeb’s potential for carcinogenicity is due to the formation of the metabolite, ETU, which is 

classified as a probable human carcinogen (B2). Mancozeb’s cancer risk is calculated by estimating 

exposure to mancozeb-derived ETU and using the ETU cancer potency factor (Q1

*

) of 6.01 x 10 -2

(mg/kg/day)-1to quantitate risk.

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). UFL = use of a LOAEL to extrapolate a 

NOAEL. UFS = use of a short-term study for long-term risk assessment. UFDB = to account for the absence of key 

data (i.e., lack of a critical study). FQPA SF = FQPA Safety Factor. PAD = population adjusted dose (a = acute, c 

= chronic). RfD = reference dose. MOE = margin of exposure. LOC = level of concern. N/A = not applicable.

Table 4.3.3 Summary of Toxicological Doses and Endpoints for ETU for Use in Dietary and NonOccupational Human Health Risk Assessments 

Exposure PoD Safety Factors RfD, PAD, LoC Study and Tox

ETU Acute Dietary Exposure

Acute Dietary 

(General Pop, 

including Infants 

and Children)

N/A N/A N/A A study with acute toxicity applicable 

to the general population was not 

identified.

Acute Dietary

(Females 13-49 

years old)

NOAEL= 5 

mg/kg/day

UFA= 10x

UFH = 10x

FQPA UFDB = 

10x

Acute RfD = 0.05 

mg/kg/day

aPAD = 0.005 

mg/kg/day

Developmental Rat Toxicity

MRID No. 45937601 (1973)

LOAEL = 10 mg/kg/day, based on 

hydrocephaly and other malformations
Mancozeb Human Health Risk Assessment DP Nos. 411742 and 411764

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Table 4.3.3 Summary of Toxicological Doses and Endpoints for ETU for Use in Dietary and NonOccupational Human Health Risk Assessments 

Exposure PoD Safety Factors RfD, PAD, LoC Study and Tox

ETU Chronic Dietary Exposure

Chronic Dietary 

(Females 13-49 

years of age and 

Children < 6 

years)

NOAEL= 0.18 

mg/kg/day

UFA= 10x

UFH = 10x

FQPA UFDB = 

10x

Chronic RfD = 0.0018

mg/kg/day

cPAD = 0.00018

mg/kg/day

Dog Chronic Oral Toxicity

MRID 42338101 (1992)

LOAEL= 1.99 mg/kg/day based on 

thyroid toxicity

Chronic Dietary 

(Adult Males, 

Females >49 

years, Children ≥ 

6 years)

NOAEL= 0.18 

mg/kg/day

UFA= 10x

UFH = 10x

FQPA SF = 1x

Chronic RfD = 0.0018

mg/kg/day

cPAD = 0.0018

mg/kg/day

Dog Chronic Oral Toxicity

MRID 42338101 (1992)

LOAEL= 1.99 mg/kg/day based on 

thyroid toxicity

ETU Incidental Oral Exposure

Short -

Term Oral 

(Children < 6 

years of age)

NOAEL= 7 

mg/kg/day

UFA= 10x

UFH=10x

FQPA UFDB = 10x

LOC = 1000 4-week range-finding dog study

MRID 41863401 (1989)

LOAEL= 34 mg/kg/day based on 

thyroid toxicity

ETU Residential Dermal Exposure

Dermal Short and

IntermediateTerm (Children` < 

6 years of age)

NOAEL= 7 

mg/kg/day

UFA= 10x

UFH=10x

FQPA UFDB = 10x

LOC = 1000 4-week range-finding dog study

MRID 41863401 (1989)

LOAEL= 34 mg/kg/day based on 

thyroid toxicity

Dermal Short and

IntermediateTerm (Adult 

Males, Females 

>49 years, 

Children ≥ 6 

years)

NOAEL= 7 

mg/kg/day

UFA= 10x

UFH=10x

FQPA SF= 1x

LOC = 100 4-week range-finding dog study

MRID 41863401 (1989)

LOAEL= 34 mg/kg/day based on 

thyroid toxicity

Dermal Short and 

IntermediateTerm (Females 

13-49 years old)

NOAEL= 5 

mg/kg/day

UFA= 10x

UFH=10x

FQPA UFDB = 10x

LOC = 1000 Developmental Rat Toxicity

MRID No. 45937601 (1973)

LOAEL = 10 mg/kg/day, based on 

hydrocephaly and other malformations

Dermal LongTerm 

(Females 13-49 

years of age and 

Children < 6 

years)

NOAEL= 

0.18 

mg/kg/day

UFA= 10x

UFH=10x

FQPA UFDB = 10x

LOC = 1000 Dog Chronic Oral Toxicity

MRID 42338101 (1992)

LOAEL= 1.99 mg/kg/day based on 

thyroid toxicity

Dermal LongTerm 

(Adult Males, 

Females >49 

years, Children ≥ 

6 years)

NOAEL= 

0.18 

mg/kg/day

UFA= 10x

UFH=10x

FQPA SF= 1x

LOC = 100 Dog Chronic Oral Toxicity

MRID 42338101 (1992)

LOAEL= 1.99 mg/kg/day based on 

thyroid toxicity

ETU Residential Inhalation Exposure

Inhalation Short 

and IntermediateTerm (Children < 

6 years of age)

NOAEL= 7 

mg/kg/day

UFA= 10x

UFH=10x

FQPA UFDB = 10x

LOC = 1000 4-week range-finding dog study

MRID 41863401 (1989)

LOAEL= 34 mg/kg/day based thyroid 

toxicity

Inhalation Short 

and IntermediateTerm (Adult 

Males, Females 

>49 years, 

Children ≥ 6 

years)

NOAEL= 7 

mg/kg/day

UFA= 10x

UFH=10x

FQPA SF= 1x

LOC = 100 4-week range-finding dog study

MRID 41863401 (1989)

LOAEL= 34 mg/kg/day based thyroid 

toxicity
Mancozeb Human Health Risk Assessment DP Nos. 411742 and 411764

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Table 4.3.3 Summary of Toxicological Doses and Endpoints for ETU for Use in Dietary and NonOccupational Human Health Risk Assessments 

Exposure PoD Safety Factors RfD, PAD, LoC Study and Tox

Inhalation Short 

and IntermediateTerm (Females 

13-49 years old)

NOAEL= 5 

mg/kg/day

UFA= 10x

UFH=10x

FQPA UFDB = 10x

LOC = 1000 Developmental Rat Toxicity

MRID No. 45937601 (1973)

LOAEL = 10 mg/kg/day, based on 

hydrocephaly and other malformations

Inhalation LongTerm (Females 

13-49 years of age 

and Children < 6 

years)

NOAEL= 

0.18 

mg/kg/day

UFA= 10x

UFH=10x

FQPA UFDB = 10x

LOC = 1000 Dog Chronic Oral Toxicity

MRID 42338101 (1992)

LOAEL= 1.99 mg/kg/day based on 

thyroid toxicity

Inhalation LongTerm (Adult 

Males, Females 

>49 years, 

Children ≥ 6 

years)

NOAEL=

0.18mg/kg/da

y

UFA= 10x

UFH=10x

FQPA SF= 1x

LOC = 100 Dog Chronic Oral Toxicity

MRID 42338101 (1992)

LOAEL= 1.99 mg/kg/day based on 

thyroid toxicity

ETU Cancer

Cancer (all routes) Q1

*

= 6.01 x 

10 -2

(mg/kg/day)-1

ETU is classified as a Group B2 carcinogen with a linear low-dose extrapolation 

approach for human risk assessment based on liver tumors in female mice.

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). UFL = use of a LOAEL to extrapolate a 

NOAEL. UFS = use of a short-term study for long-term risk assessment. UFDB = to account for the absence of key 

data (i.e., lack of a critical study). FQPA SF = FQPA Safety Factor. PAD = population adjusted dose (a = acute, c 

= chronic). RfD = reference dose. MOE = margin of exposure. LOC = level of concern. N/A = not applicable.

Table 4.3.4 Summary of Toxicological Doses and Endpoints for ETU for Use in Occupational Human Health 

Risk Assessments 

Exposure PoD Safety 

Factors RfD, PAD, LoC Study and Tox

ETU Occupational Dermal Exposure

Dermal Short and

Intermediate-Term 

(Adult Males, 

Females >49 

years)

NOAEL= 7 

mg/kg/day

UFA= 10x

UFH=10x

LOC = 100 4-week range-finding dog study

MRID 41863401 (1989)

LOAEL= 34 mg/kg/day based on 

thyroid toxicity

Dermal Short and 

Intermediate-Term 

(Females 13-49 

years old)

NOAEL= 5 

mg/kg/day

UFA= 10x

UFH=10x

UFDB = 10x

LOC = 1000 Developmental Rat Toxicity

MRID No. 45937601 (1973)

LOAEL = 10 mg/kg/day, based on 

hydrocephaly and other malformations

Dermal LongTerm 

(Females 13-49 

years of age)

NOAEL= 

0.18 

mg/kg/day

UFA= 10x

UFH=10x

UFDB = 10x

LOC = 1000 Dog Chronic Oral Toxicity

MRID 42338101 (1992)

LOAEL= 1.99 mg/kg/day based on 

thyroid toxicity

Dermal LongTerm 

(Adult Males, 

Females >49 

years)

NOAEL= 

0.18 

mg/kg/day

UFA= 10x

UFH=10x

LOC = 100 Dog Chronic Oral Toxicity

MRID 42338101 (1992)

LOAEL= 1.99 mg/kg/day based on 

thyroid toxicity

ETU Occupational Inhalation Exposure
Mancozeb Human Health Risk Assessment DP Nos. 411742 and 411764

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Table 4.3.4 Summary of Toxicological Doses and Endpoints for ETU for Use in Occupational Human Health 

Risk Assessments 

Exposure PoD Safety 

Factors RfD, PAD, LoC Study and Tox

Inhalation Short 

and IntermediateTerm (Adult 

Males, Females 

>49 years)

NOAEL= 7 

mg/kg/day

UFA= 10x

UFH=10x

LOC = 100 4-week range-finding dog study

MRID 41863401 (1989)

LOAEL= 34 mg/kg/day based thyroid 

toxicity

Inhalation Short 

and IntermediateTerm (Females 

13-49 years old)

NOAEL= 5 

mg/kg/day

UFA= 10x

UFH=10x

UFDB = 10x

LOC = 1000 Developmental Rat Toxicity

MRID No. 45937601 (1973)

LOAEL = 10 mg/kg/day, based on 

hydrocephaly and other malformations

Inhalation LongTerm (Females 

13-49 years of 

age)

NOAEL= 

0.18 

mg/kg/day

UFA= 10x

UFH=10x

UFDB = 10x

LOC = 1000 Dog Chronic Oral Toxicity

MRID 42338101 (1992)

LOAEL= 1.99 mg/kg/day based on 

thyroid toxicity

Inhalation LongTerm (Adult 

Males, Females 

>49 years)

NOAEL=

0.18mg/kg/da

y

UFA= 10x

UFH=10x

LOC = 100 Dog Chronic Oral Toxicity

MRID 42338101 (1992)

LOAEL= 1.99 mg/kg/day based on 

thyroid toxicity

ETU Cancer

Cancer (all routes) Q1

*

= 6.01 x 

10 -2

(mg/kg/day)-1

ETU is classified as a Group B2 carcinogen with a linear low-dose extrapolation 

approach for human risk assessment based on liver tumors in female mice.

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). UFL = use of a LOAEL to extrapolate a 

NOAEL. UFS = use of a short-term study for long-term risk assessment. UFDB = to account for the absence of key 

data (i.e., lack of a critical study). FQPA SF = FQPA Safety Factor. PAD = population adjusted dose (a = acute, c 

= chronic). RfD = reference dose. MOE = margin of exposure. LOC = level of concern. N/A = not applicable.

5.0 Dietary Exposure and Risk Assessment 

5.1 Residues of Concern Summary and Rationale

The residues of concern for risk assessment and the residues to be included in the tolerance 

expression for mancozeb are summarized in the table below. For plants and livestock 

commodities, the tolerance expression for mancozeb includes parent mancozeb, measured as 

CS2. For risk assessment, however, both parent mancozeb and ETU residues must be considered. 

Mancozeb, as well as the other EBDC compounds, is short lived in soil and water. The EBDC 

degradate ETU is highly water soluble, highly vulnerable to indirect photolysis, and is 

moderately mobile. ETU has a relatively high vapor pressure, but the high solubility reduces the 

possibility of losses from surface water due to volatilization. In drinking water, the residue of 

concern for risk assessment is the degradate ETU.

Further information on the metabolism and degradation may be found in the risk assessment 

dated 6/11/07 (D327307 & D327318).
Mancozeb Human Health Risk Assessment DP Nos. 411742 and 411764

Page 29 of 77

Table 5.1 Summary of Metabolites and Degradates to be included in the Risk Assessment and Tolerance 

Expression

Matrix Residues included in Risk 

Assessment

Residues included in 

Tolerance Expression

Plants Primary Crop Mancozeb & ETU Mancozeb, measured as CS2

Rotational Crops No data are available. Identified as a data gap in the RED.1

Livestock Ruminant Mancozeb & ETU Mancozeb, measured as CS2

Drinking Water ETU only Not Applicable

1 A confined rotational crop study was required in the 2005 mancozeb Reregistration Eligibility Decision and remains 

outstanding. HED is not requiring the study as a condition of registration to support these new uses because orchard crops are 

not rotated after commodity harvest.

5.2 Food Residue Profile

Application of mancozeb to food crops results primarily in surface residues. For the proposed 

uses on walnuts and tangerines, adequate crop field trial data were provided and are the basis for 

the recommended tolerance levels, as well as the basis for the information used for the dietary 

risk assessment.

The residue chemistry database for mancozeb is adequate to support proposed use on walnuts 

and imported tangerines. The nature of the residue in plants is adequately understood based on 

prior metabolism studies made with potato, soybean, sugar beet, tomato, and wheat. The nature 

of the residue is also adequately understood in livestock based upon previous metabolism studies 

made on goats and poultry. HED has concluded that the residue of concern for the tolerance 

enforcement of all regulated commodities is mancozeb calculated as CS2. In regard to risk 

assessment, both the EBDC parent mancozeb and its degradate ETU are to be considered for 

evaluation. There are adequate methods available for the enforcement of crop tolerances for 

determining dithiocarbamate residues in/on plant commodities. Adequate storage stability data 

are available which demonstrate that residues of mancozeb and ETU are stable when stored 

frozen in almond nutmeats for durations of 10 and 15.7 months, respectively. Stability data 

demonstrate that residues of mancozeb and ETU are stable in/on tangerines for at least 160 days

in frozen storage.

In the submitted walnut field trials, there were detectable residues of mancozeb, but ETU 

residues were non-detectable or just above the limit of detection. In the tangerine field trials, 

both mancozeb and ETU were detected, but levels of ETU were significantly lower than those of 

mancozeb. The results of residue decline studies in tangerines showed that residues of mancozeb 

decrease with an increasing PHI.

No processing data are required to support this proposed use on walnuts. Rotational crop data 

are also not needed to support this requested use because walnut trees are not rotated following 

harvest. There are no animal feed items associated with walnuts. 
Mancozeb Human Health Risk Assessment DP Nos. 411742 and 411764

Page 30 of 77

No processing or rotational crop data are required to support the proposed use of mancozeb on 

imported tangerines. However, a processing study for tangerine juice demonstrated significant 

residue reduction. Because imported tangerines are not expected to be processed into dried pulp 

in the U.S., there are no animal feed items associated with imported tangerines.

5.3 Water Residue Profile

Mancozeb is short lived in soil and water and would therefore not be expected to remain in 

surface water long enough to reach a location that would supply water for human consumption,

whether from surface or ground water. However, mancozeb’s degradate, ETU, is highly water 

soluble and may reach both surface and ground water under some conditions; therefore, a 

drinking water assessment for ETU was conducted to support various EBDC pesticide uses for 

the 2005 Reregistration Eligibility Decision (RED) (D286871, 5/15/03). It should be noted that 

the assessment conducted for the RED combined ETU from all sources of EDBC pesticides, 

including mancozeb. After consideration of the proposed application rates and use patterns for 

walnuts in comparison to the maximum application rates and use patterns used in the most 

recent drinking water assessment (for almond use), as well as considering the appropriateness of 

extrapolating monitoring data to these new uses, EFED has determined that the previously 

derived EDWCs for ETU can be used in the human health risk assessment to support the 

proposed new use on walnuts (the proposed tangerine use is not for use on domestically grown 

tangerines) (D397306, 7/3/12).

ETU surface water estimated drinking water concentrations were based both on PRZM-EXAMS 

modeling information and available monitoring data. The acute (peak) surface water EDWC 

ranged from 0.1 ppb from monitoring data to 25.2 ppb as a model output. The chronic/cancer 

surface water value provided by EFED was 0.1 ppb based on monitoring data.

ETU ground water EDWC values were taken from a targeted monitoring study in Florida. EFED 

provided a value of 0.21 ppb from the monitoring data to be used in the acute, chronic and cancer 

risk assessments. This value represents the single highest concentration found in untreated 

water sampled from one of 84 sites over a period from 2001- 2004. No detectable residues of 

ETU were found in treated water at the 84 sites, including the two sites where ETU residues 

were found in untreated water. 

A more detailed summary of the ETU drinking water assessment conducted for the RED can be 

found in the human health risk assessment developed for the RED (D317371, 6/3/05, K. Farwell) 

and additional details on the drinking water assessment are contained in the EFED drinking 

water assessment memorandum entitled Revision No. 2: Estimated Drinking Water 

Concentration of Ethylenebisdithocarbamate (EBDC) Degradate Ethylenethiourea (ETU) for the 

Use in Human Health Risk Assessment, D323143 and 323141, 8/11/06, M. Ruhman.

ETU estimated drinking water concentrations provided by EFED are summarized below.
Mancozeb Human Health Risk Assessment DP Nos. 411742 and 411764

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Table 5.3 Summary of Estimated Surface Water and Ground Water Concentrations for 

ETU.

ETU from all EBDC pesticides including mancozeb

Surface Water Conc., ppb a Ground water Conc., ppb b

Acute 0.1 – 25.2 0.21

Chronic (non-cancer) 0.1 0.21

Chronic (cancer) 0.1 0.21

a

Surface water EDWCs were derived from both monitoring and modeling data. A range of acute surface water 

concentrations was provided. The lower end of the range was based on monitoring data and the upper end of the 

range was based on EPA PRZM and EXAMS models. Chronic/Cancer EDWCs were based on monitoring data.

b Ground water EDWCs were taken from a community well monitoring program and represent the single highest 

value found at any sampling for 84 sites.

Bolded values used in the dietary risk assessment.

5.4 Dietary Risk Assessment

5.4.1 Description of Residue Data Used in Dietary Assessment

Acute, chronic, and cancer aggregate dietary food and drinking water exposure and risk 

assessments were conducted using the Dietary Exposure Evaluation Model software with the 

Food Commodity Intake Database (DEEM-FCID) Version 3.16. This software uses 2003-2008 

food consumption data from the U.S. Department of Agriculture’s (USDA’s) National Health 

and Nutrition Examination Survey, What We Eat in America, (NHANES/WWEIA). 

Field trial or monitoring data from the EBDC/ETU Market Basket Survey, percent crop treated 

information, and processing study results were utilized to assess the established uses of 

mancozeb. The monitoring data were used for several commodities (corn, cucumber, onion, 

pumpkin, potato, squash, starfruit, tomato, meat, and milk). For evaluation of the proposed new 

uses and tolerances, field trial data, processing factors, percent crop treated data based on Section 

18 usage for walnuts, and percent imported commodity in domestic consumption data on 

tangerines for mancozeb were used to refine residue estimates. Modeling estimates 

(PRZM/EXAMS) for surface water (almond use scenario) were used for ETU EDWCs in the 

acute assessment and well monitoring data were used for ETU EDWCs for ground water for the 

chronic and cancer assessments. The dietary analyses performed for mancozeb were for food 

only since it is known to degrade quickly in the environment and is not expected to reach 

drinking water sources. The dietary analyses performed for ETU were for both food and 

drinking water.

For the probabilistic acute dietary exposure analysis, the entire distributions of residue data from 

field trials or monitoring data were used to generate residue distribution files (RDFs) for 

commodities that are considered to be not blended or partially blended. For commodities 

considered to be blended in this analysis, the average residues incorporating the likely maximum 

estimated % CT was used as a point estimate. 
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Chronic anticipated residues were calculated from field trial or monitoring data for mancozeb 

and ETU. Averages of the field trials were used for the walnuts and tangerines, while field trial 

and market basket survey data were used for established uses. 

5.4.2 Percent Crop Treated Used in Dietary Assessment

For the existing uses of mancozeb, BEAD provided a compilation of percent crop treated (%CT) 

data (D402049, 6/7/12, J. Alsadek). Additional %CT data for celery, barley, rice and cranberry, 

as well as percent import data for tangerines and projected crop treated estimate for walnuts, 

were provided by BEAD through email correspondence (see D402043, Attachments 6, 7 and 8). 

The following maximum percent crop treated estimates were used in the acute dietary risk 

assessment for the following crops that are currently registered for mancozeb: almonds: 2.5%; 

apples: 45%; asparagus: 30%; barley: 2.5%; broccoli: 9%; cabbage: 47%; cantaloupes: 15%; 

carrots: 2.5%; celery: 2.5%; corn: 2.5%; cranberries: 20%; cucumbers: 50%; grapes: 20%; 

lettuce, head: 66%; lettuce, other: 61%; oats: 1%; onions: 70%; peanuts: 2.5%; pears: 50%; 

peppers: 48%; potatoes: 65%; pumpkins: 15%; rice: 2.5%; spinach: 2.5%; squash: 30%; sugar 

beets: 2.5%; sweet corn: 15%; tomatoes: 50%; watermelons: 50%; and wheat: 2.5%. A percent 

import value of 99% was used for banana.

The following average percent crop treated estimates were used in the chronic and cancer dietary 

risk assessments for the following crops that are currently registered for mancozeb: almonds: 

1%; apples: 40%; asparagus: 15%; barley: 1%; broccoli: 7%; cabbage: 42%; cantaloupes: 5%; 

carrots: 1%; celery: 1%; cherries: 1%; corn: 1%; cranberries: 20%; cucumbers: 25%; grapes: 

10%; lettuce, head: 58%; lettuce, other: 59%; oats: 1%; onions: 60%; peanuts: 2.5%; pears: 40%; 

peppers: 43%; potatoes: 55%; pumpkins: 10%; rice: 1%; spinach: 1%; squash: 20%; sugar beets: 

1%; sweet corn: 5%; tomatoes: 25%; watermelons: 40%; and wheat: 1%. A percent import value 

of 99% was used for banana.

A maximum percent crop treated projected estimate of 50% for walnuts and a maximum percent 

import consumption value of 35% for tangerines were used in the acute dietary risk assessment 

to support the proposed mancozeb uses. An average percent crop treated estimate of 40% for 

walnuts as well as an average percent imported commodity in domestic consumption value of 

29% for tangerines were used in the chronic and cancer dietary risk assessments. As a further 

refinement, the commodity having the highest %CT results with livestock feed uses had these 

values applied to meat and milk (potato; 65% CT maximum for acute and 65% CT average for 

chronic).

5.4.3 Acute Dietary Risk Assessment

A highly refined probabilistic acute dietary exposure and risk assessment was conducted for both 

mancozeb and for mancozeb-derived ETU to support the proposed new uses of mancozeb. Acute 

dietary risk estimates are below HED’s level of concern for parent mancozeb (food only; 

mancozeb is not expected in drinking water) for all population subgroups. The highest exposure 

and risk estimates were for children 1-2 years old at 9.9% of the aPAD. 

 
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The mancozeb metabolite and environmental degradate ETU has a toxicological endpoint for 

acute risk assessment only for the population subgroup of females 13-49 years old. Acute risk 

estimates for females 13-49 years old are below HED’s level of concern for ETU at 58% of the 

aPAD (food and water).

See Tables 5.4.6.1 and 5.4.6.2 for a summary of the acute dietary exposure and risk estimates.

5.4.4 Chronic Dietary Risk Assessment

A highly refined chronic dietary exposure and risk assessment was conducted for both mancozeb 

and for mancozeb-derived ETU to support the proposed new uses of mancozeb. The chronic risk 

estimates are below HED’s level of concern for mancozeb and ETU for the general U.S. 

population and all population subgroups. For mancozeb, the most highly exposed population 

subgroup is children ages 1-2 with an estimate of 2.3% of the cPAD (food only; mancozeb is not 

expected in drinking water). For from mancozeb sources, most highly exposed population 

subgroup is children ages 1-2 with an estimate of 51% of the cPAD (food and water).

See Tables 5.4.6.1 and 5.4.6.2 for a summary of the chronic dietary exposure and risk estimates.

5.4.5 Cancer Dietary Risk Assessment

The cancer risk estimate associated with exposure to ETU in food and water, as a result of new 

and proposed mancozeb uses, is 2 x 10-6for the general U.S. population.

See Table 5.4.6.2 for a summary of the cancer dietary exposure and risk estimates.

5.4.6 Summary Table

Table 5.4.6.1 Summary of Dietary (Food Only) Exposure and Risk for Mancozeb

Population Subgroup

Acute Dietary

(99.9th Percentile) Chronic Dietary Cancer

Dietary 

Exposure 

(mg/kg/day)

% aPAD*

Dietary 

Exposure

(mg/kg/day)

% cPAD*

Dietary 

Exposure

(mg/kg/day)

Risk

General U.S. Population 0.014388 < 1. 0.000107 < 1. Mancozeb’s potential for 

carcinogenicity is due to the 

formation of the metabolite 

ETU which is classified as a 

probable human carcinogen 

(B2). Mancozeb’s cancer 

risk is calculated by 

estimating exposure to 

mancozeb-derived ETU and 

using the ETU cancer 

potency factor (Q1

*

) of 6.01 x

All Infants (<1 year old) 0.011425 2.3 0.000086 < 1.

Children 1-2 years old 0.049471 9.9 0.000374 2.3

Children 3-5 years old 0.036223 7.2 0.000260 1.6

Children 6-12 years old 0.017499 < 1. 0.000119 < 1.

Youth 13-19 years old 0.009590 < 1. 0.000064 < 1.

Adults 20-49 years old 0.009912 < 1. 0.000090 < 1.

Adults 50-99 years old 0.008187 < 1. 0.000097 < 1.
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Table 5.4.6.1 Summary of Dietary (Food Only) Exposure and Risk for Mancozeb

Population Subgroup

Acute Dietary

(99.9th Percentile) Chronic Dietary Cancer

Dietary 

Exposure 

(mg/kg/day)

% aPAD*

Dietary 

Exposure

(mg/kg/day)

% cPAD*

Dietary 

Exposure

(mg/kg/day)

Risk

Females 13-49 years old 0.011634 9.0 0.000101 < 1. 10 -2

(mg/kg/day)-1to provide 

a quantitative estimate of 

risk.

. *The values for the highest exposed population for each type of risk assessment is bolded

Table 5.4.6. 2 Summary of Dietary (Food and Water) Exposure and Risk for ETU (derived from 

mancozeb)

Population Subgroup

Acute Dietary

(99.9th Percentile) Chronic Dietary Cancer

Dietary 

Exposure 

(mg/kg/day)

% aPAD*

Dietary 

Exposure

(mg/kg/day)

% cPAD*

Dietary 

Exposure

(mg/kg/day)

Risk

General U.S. Population

NA NA

0.000030 1.7 0.000030 2 x 10-6

All Infants (<1 year old) 0.000045 25

NA NA

Children 1-2 years old 0.000092 51

Children 3-5 years old 0.000062 35

Children 6-12 years old 0.000033 1.8

Youth 13-19 years old 0.000022 1.2

Adults 20-49 years old 0.000027 1.5

Adults 50-99 years old 0.000026 1.5

Females 13-49 years old 0.002901 58 0.000028 15

*The values for the highest exposed population for each type of risk assessment is bolded

6.0 Residential (Non-Occupational) Exposure/Risk Characterization

There are no new residential uses being proposed for mancozeb at this time; however, residential 

uses that could result in mancozeb and ETU exposure (i.e., home gardeners applying mancozeb 

to vegetables and golfers contacting mancozeb treated turf after application) have been 

reassessed in this document to reflect updates to toxicology endpoint selections, updates to the 

Levels of Concern (LOCs), and 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 previous assessment for residential exposures may be 

found in D327307 & D327318; D. Davis, et al., 6/11/07. Reassessed exposures and risks from 

the various residential scenarios are summarized here since those values are required for the 

aggregate risk assessment to support the proposed new use that is the subject of this action.
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6.1 Residential Handler Exposure

The existing residential handler scenario identified for mancozeb is for the application of 

mancozeb in home gardens (i.e., vegetables). The anticipated use patterns and current labeling 

indicate that backpack, manually pressurized handwand sprayers and hose-end sprayers could be 

used by the homeowner to make mancozeb applications. Residential handler risk estimates were 

assessed for mancozeb (inhalation only; dermal toxicity is not expected for mancozeb) and it’s 

degradate ETU (combined dermal and inhalation). Non-cancer short-term assessments were 

performed for both mancozeb and ETU. A cancer assessment was also performed for ETU. 

There are no risk estimates of concern for adults applying mancozeb to home gardens. The 

details regarding the residential handler assumptions and calculated risk estimates are outlined 

below (for additional details see D411769, Mancozeb: Occupational and Residential Risk 

Assessment to Support Request for Section 3 Registrations on Walnuts).

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

following scenarios: 

1. Adults Mixing/Loading/Applying liquids by Manually-pressurized handwand;

2. Adults Mixing/Loading/Applying liquids by Hose-End Sprayer; and

3. Adults Mixing/Loading/Applying liquids by Backpack.

Residential Handler Exposure Data and Assumptions

Only inhalation MOEs were calculated for short term mancozeb exposures because no effects 

were observed in a mancozeb 28 day dermal toxicity study. Risk calculations were also 

performed to assess the risk of mancozeb’s degradate ETU.

The non-cancer risk calculations for exposures by residential handlers to ETU were calculated in 

the same manner as for mancozeb with additional conversions that account for the direct 

absorption of ETU as well as the metabolic conversion of absorbed mancozeb into ETU. The 

daily exposure was calculated from environmental sources of ETU (direct exposure via dermal 

or inhalation absorption) and from metabolic sources of ETU (mancozeb metabolically 

converted to ETU). 

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

handler risk assessments. Each assumption and factor is detailed below.

Application Rate:

According to registered labels a mancozeb formulation product (i.e., Dithane F-45; EPA Reg. 

62719-396) can be applied to home garden vegetables at a maximum single application rate of 

2.4 lb ai/acre. Tank mix stability studies submitted to, and reviewed by, the Agency in 1991 

indicated that 0.1 percent of the mancozeb parent converted to ETU during mixing/loading and 

0.2 percent converted to ETU during application (D327307 & D327318; D. Davis, 6/11/07). 
Mancozeb Human Health Risk Assessment DP Nos. 411742 and 411764

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Unit Exposures and Area Treated or Amount Handled: Unit exposure values and estimates for 

area treated or amount handled were taken from HED’s 2012 Residential SOPs 

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

Body Weight

The standard body weight for the general population (80 kg) was used for assessing 

mancozeb inhalation non-cancer risks and ETU cancer risks since the endpoints selected 

were not developmental and/or fetal effects. 

A body weight of 69 kg was used for assessing ETU non-cancer risks since the POD are 

based on developmental and/or fetal effects.

Risk estimate results for both population sub-groups (i.e., females 13 to 49 years old, and 

males and females>49 years old) are presented since the LOCs for these lifestage 

population groups are different.

Absorption Factors

A dermal absorption factor of 1 % was used for mancozeb. A dermal absorption factor of 26 % 

was used for ETU. A metabolic conversion factor of 7.5 % 1of the absorbed mancozeb dose is 

used to calculate the ETU dose due to in-vivo metabolism. Since no inhalation absorption data 

are available, toxicity by the inhalation route is considered to be equivalent to the estimated 

toxicity by the oral route of exposure.

Exposure Duration: 

Residential handler exposure is expected to be short-term in duration. Intermediate-term 

exposures are not likely because of the intermittent nature of applications by homeowners.

Residential Handler Non-Cancer Exposure and Risk Estimate Equations

The non-cancer risk calculations for exposures to residential handlers were calculated in a 

similar manner as for occupational handlers. The algorithms used to estimate exposure and dose 

for residential handlers can be found in the 2012 Residential SOPs 

(http://www.epa.gov/pesticides/science/residential-exposure-sop.html) and in Appendix A of

D411769).

Summary of Residential Handler Non-Cancer Exposure and Risk Estimates for Mancozeb

Residential handler inhalation risk estimates are not of concern (MOE ≥ 1000 for adult females 

13-49 years old and MOE ≥ 100 for other adults (males, females >49 years old)). Inhalation 

MOEs for mixing/loading/applying liquid formulation to vegetable gardens scenarios range from 

170,000 for backpack sprayer applications to 20 million for hose-end sprayer applications. A 

summary of inhalation risk estimates for residential handlers can be found in Table 6.1.1.

Summary of Residential Handler Non-Cancer Exposure and Risk Estimates for ETU from 

Mancozeb

Residential handler risk estimates are not of concern (MOE ≥ 1000 for adult females 13-49 years 

old and MOE ≥ 100 for other adults (males, females >49 years old)). MOEs range from 32,700 

(mixing/loading/applying liquid formulation to vegetable gardens by backpack) to 130,000

 

1 A. Kocialski, 09/12/1989. Memo: Establishment of an in-vivo Metabolic Conversion Factor of 7.5%for all 

Ethylene Bis(Dithio) Carbamates (EBDCS)when Converting EBDCSs to Ethylene Thiourea (ETU) in- vivo.
Mancozeb Human Health Risk Assessment DP Nos. 411742 and 411764

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(mixing/loading/applying liquid formulation to vegetable gardens by hose-end sprayer). A 

summary of ETU non-cancer exposure risk estimates for residential handlers can be found in

Table 6.1.2.

Combining Exposures/Risk Estimates:

The non-cancer risk calculations for exposures to residential handlers to ETU were calculated in 

a similar manner as for occupational handlers. Dermal and inhalation risk estimates were 

combined in this assessment, since the toxicological effects for these exposure routes were 

similar. ETU dermal and inhalation risk estimates were combined using the following formula:

ETU Total MOE = Point of Departure (mg/kg/day) / Combined dermal + inhalation dose (mg/kg/day)
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Table 6.1.1 Non-cancer (Short-term) Residential Handler Exposure and Risk Estimates for Mancozeb.

Exposure Scenario Level of 

Concern

Inhalation Unit Exposure 2

(mg/lb ai)

Maximum Application 

Rate1

(lb ai/ft2)

Area Treated or 

Amount Handled 

Daily2

Inhalation

Dose

MOE4

(mg/kg/day)3

Mixer/Loader/Applicator (Adult Males, Females >49 years)

Home Gardens, liquid concentrate, Manuallypressurized handwand

30

0.018

5.5 x 10-51200 ft2

1.35 x 10-51.6 x 10 6

Home Gardens, liquid concentrate, backpack 0.14 1.05 x 10-4200,000

Home Gardens, liquid concentrate, Hose-end 

sprayer

0.0014 1.05 x 10-620 x 10 6

Mixer/Loader/Applicator (Adult Females 13-49 years)

Home Gardens, liquid concentrate, Manuallypressurized handwand (Females 13-49 years)

300

0.018

5.5 x 10-51200 ft2

1.57 x 10-51.3 x 10 6

Home Gardens, liquid concentrate, backpack 0.14 1.22 x 10-4170,000

Home Gardens, liquid concentrate, Hose-end 

sprayer

0.0014 1.22 x 10-617 x 10 6

1 Based on registered label (EPA Reg. 62719-396).

2 Unit exposure values and estimates for area treated or amount handled based on Exposure Science Advisory Council 2012 Residential SOPs: 

http://www.epa.gov/pesticides/science/residential-exposure-sop.html

3

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 

gallons/day) / BW (kg).

4

Inhalation MOE = Inhalation NOAEL (mg/kg/day) / Inhalation Dose (mg/kg/day)
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Table 6.1.2 Non-cancer (Short-term) Residential Handler Exposure and Risk Estimates for ETU from Mancozeb.

Exposure Scenario Level of 

Concern

Dermal 

Unit 

Exposure

(mg/lb ai)

Inhalation 

Unit 

Exposure 1

(mg/lb ai)

Maximum 

Application 

Rate2

(lb ai/ft2)

Area Treated 

or Amount 

Handled 

Daily1

ETU Dermal Dose

(mg/kg/day)5

ETU Inhalation Dose

(mg/kg/day) 5

Total ETU 

Dose 

(mg/kg/day)6

MOE7

ETU from 

Direct 

Exposure

(Present in

Tank Mix ) 3

ETU 

Metabolized 

from 

Mancozeb4

ETU from 

Direct 

Exposure 

(Present in

Tank Mix ) 3

ETU 

Metabolized 

from 

Mancozeb4

Mixer/Loader/Applicator (Adult Males, Females >49 years)

Home Gardens, liquid concentrate, 

Manually-pressurized handwand

100

63 0.018

5.5 x 10-51200 ft2

2.46 x 10-53.54 x 10-52.7 x 10-81.01 x 10-66.10 x 10-5110,000

Home Gardens, liquid concentrate, 

backpack 130 0.14 5.07 x 10-5

7.31 x 10-52.10 x 10-77.88 x 10-61.32 x 10-453,000

Home Gardens, liquid concentrate, 

Hose-end sprayer 58 0.0014 2.26 x 10-5

3.26 x 10-52.10 x 10-97.8 x 10-85.53 x 10-5130,000

Mixer/Loader/Applicator (Adult Females 13-49 years)

Home Gardens, liquid concentrate, 

Manually-pressurized handwand 

1000

63 0.018

5.5 x 10-51200 ft2

2.84 x 10-54.10 x 10-53.13 x 10-81.17 x 10-67.07 x 10-570,600

Home Gardens, liquid concentrate, 

backpack 130 0.14 5.87 x 10-5

2.12 x 10-53.43 x 10-79.13 x 10-61.53 x 10-432,700

Home Gardens, liquid concentrate, 

Hose-end sprayer 58 0.0014 2.62 x 10-5

3.78 x 10-52.43 x 10-99.13 x 10-86.41 x 10-578,000

1 Unit exposure values and estimates for area treated or amount handled based on ExpoSAC 2012 Residential SOPs: http://www.epa.gov/pesticides/science/residential-exposuresop.html

2 Based on registered label (EPA Reg. 62719-396).

 Daily Exposure = 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) x DAF (%)

3 ETU Average Daily Dose from Direct Exposure to ETU (mg/kg/day) = [Daily Exposure (mg ai/day) * Absorption (%)]/ BW (kg) 

 Absorption =0.1 (for mixing and loading) or 0.2 (for application) % of mancozeb.

4 ETU Average Daily Dose From metabolic conversion of mancozeb (mg/kg/day) = [Daily Exposure (mg ai/day) * Absorption (%)*Metabolic ETU Conversion]/ BW (kg)

 7.5 percent of the absorbed mancozeb dose is metabolically converted to ETU

5 Dermal or Inhalation Dose= ETU Average Daily Dose from Direct Exposure to ETU (mg/kg/day) + ETU Average Daily Dose From metabolic conversion of mancozeb (mg/kg/day) 

6 Total ETU Dose = Total Dermal ETU Dose (mg/kg/day) + Total Inhalation ETU Dose (mg/kg/day)

7 Total MOE = NOAEL (mg/kg/day)/Total ETU Dose (mg/kg/day). ETU Short-Term Dermal and Inhalation NOAEL: 5 mg/kg/day (females 13-49); 7 mg/kg/day (males, females >49)
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Summary of Residential Handler Cancer Exposure and Risk Estimates for ETU from Mancozeb

The cancer risks to home gardeners were reassessed, as they will be used for the aggregate risk 

assessment. Further description of the assumptions and data used in the assessment may be 

found in D411769. As previously noted, mancozeb’s potential for carcinogenicity is due to the 

formation of the metabolite ETU. Cancer risks from exposure to ETU as a result of application 

of mancozeb are calculated by estimating exposure to mancozeb-derived ETU and using the 

ETU Q1

*

of 0.0601 (mg/kg/day)-1to provide a quantitative estimate of risk. 

The cancer risk calculations for exposures by residential handlers to ETU were calculated in a 

similar manner as for occupational handlers with the following assumptions: 

Days per year of Exposure

To assess cancer risk, it is assumed that residential handlers would be exposed 5 days per year.

Years per Lifetime of Exposure:

It is assumed that residential handlers would be exposed for 50 years out of a 78-year lifespan.

Lifetime Expectancy: 

Life expectancy values are from the Exposure Factors Handbook 2011 Edition Table 18-1 (U.S. 

EPA, 2011). The table shows that the overall life expectancy is 78 years based on life 

expectancy data from 2007. In 2007, the average life expectancy for males was 75 years and 80 

years for females. Based on the available data, the recommended value for use in cancer risk 

assessments is 78 years. 

The cancer risks for all M/L/A scenarios are estimated in the 10-8range for residential handlers. 

Residential handler estimated cancer risks were calculated for applicators using a backpack 

sprayer, manually pressurized and hose-end sprayer. For applicators using backpack sprayers the 

estimated cancer risk from mancozeb-derived ETU was 7 x 10-8. Residential handlers using 

manually pressurized sprayers had an estimated cancer risk of 3 x 10-8. Handlers using hose-end 

sprayers had an estimated cancer risk of 3 x 10-8. A summary of ETU cancer exposure risk 

estimates for residential handlers can be found in Table 6.1.3.
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Table 6.1.3 Residential Handler Cancer Exposure and Risk Estimates for ETU from Mancozeb. 

Crop or Target Exposure Scenario

Handler 

Dermal 

ADD1 

(mg/kg/day)

Handler

Inhalation 

ADD2 

(mg/kg/day)

Total Absorbed 

Dose

ADD

(mg/kg/day)

Total LADD 3

(mg/kg/day)3

Residential 

Handler

Cancer 

Risk 

Estimate4

Mixer/Loader/Applicator 

Home Gardens

(Vegetables)

Liquid concentrate - Manuallypressurized handwand 6.00 x 10 -5

1.04 x 10 -66.10 x 10 -55.36 x 10 -73 x 10 -8

Liquid concentrate - Backpack 1.24 x 10 -48.09 x 10 -61.32 x 10 -41.16 x 10 -6- 7 x 10 -8

Liquid concentrate - Hose-end 

sprayer 

5.52 x 10 -58.09 x 10 -85.53 x 10 -54.86 x 10 -73 x 10 -8

1 Dermal LADD = Dermal dose * Days per year of exposure *Years per lifetime of exposure / (365 days/year x 

Lifetime expectancy).

2

Inhalation LADD = Inhalation Dose * Days per year of exposure *Years per lifetime of exposure / (365 days/year 

x Lifetime expectancy).

3 Total LADD = total absorbed dose [Dermal dose + Inhalation Dose] * Days per year of exposure * Years per 

lifetime of exposure / (365 days/year x Lifetime expectancy).

4 Cancer risk estimates = LADD * Q1*

, where Q1

*

= 6.01 x 10 -2(mg/kg/day)-1.

6.2 Post-Application Exposure

Mancozeb can be used in areas that can be frequented by the general population including 

residential areas (vegetable gardens and lawns containing turf from sod farms) and golf courses. 

As a result, individuals can be exposed by entering areas that have been previously treated with 

mancozeb. An updated assessment of the most representative scenarios to be used in the 

aggregate assessment is presented below. 

In addition to the mancozeb uses on home gardens and golf courses there is a registered sod farm 

use and the treated sod could be subsequently transplanted to a residential setting. HED

considers post-application exposure resulting from this scenario to be negligible for the 

following reasons: 1) mancozeb has a post-harvest interval (PHI) of 5 days for sod; 2) it is 

unlikely that sod treated with mancozeb would be installed more than once per year; 3) 

transplanted sod requires constant and significant watering which will result in decreased 

mancozeb residues on the transplanted sod; and 4) it is unlikely that adults or children will spend 

any significant amount of time on recently transplanted sod until it is rooted which typically 

occurs around 2 weeks after transplanting. Therefore, dermal and incidental oral post-application 

scenarios were not quantitatively assessed for the sod farm use of mancozeb. There are no postapplication exposure risks of concern anticipated from the use of mancozeb on sod farms. 

The quantitative exposure/risk assessment for residential post-application exposures is based on:

home gardeners (adults and youth) harvesting vegetables from treated gardens and golfers (adults 

and youth) contacting mancozeb treated turf after application. As no dermal hazard was 

identified for mancozeb, a quantitative dermal post-application assessment (non-cancer/short-
Mancozeb Human Health Risk Assessment DP Nos. 411742 and 411764

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term and cancer) was only performed for its metabolite, ETU.

The lifestages selected for each post-application scenario are based on an analysis provided as an 

Appendix in the 2012 Residential SOPs (http://www.epa.gov/pesticides/science/residentialexposure-sop.html). These lifestages are not the only lifestages that could be potentially exposed 

for these post-application scenarios; however, the assessment of these lifestages is health 

protective for the exposures and risk estimates for any other potentially exposed lifestages.

Residential Post-application Exposure Data and Assumptions

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

post-application risk assessment. Each assumption and factor is detailed in the 2012 Residential 

SOPs (http://www.epa.gov/pesticides/science/residential-exposure-sop.html and in Appendix A 

of D411769. Assumptions regarding body weight, conversion of mancozeb to ETU, and 

absorption factors are the same as those outlined in Section 6.1 above.

Home Gardeners 

According to registered labels a mancozeb formulation product (i.e., Dithane F-45; EPA Reg. 

62719-396) can be applied to home garden vegetables at a maximum single application rate of 

2.4 lb ai/acre. Adults and children may be exposed to mancozeb-derived ETU while performing 

high contact activities (e.g., weeding, harvesting) in a residential home garden that has been 

previously treated. 

The assumptions for the residential home gardener assessment are: 

The lifestages assessed were adults and youth (children 6 to 11 years old).

Dermal exposures were assessed for the commodity that might be found in a home 

garden and led to the highest exposure (i.e., cucurbit vegetables).

Dislodgeable Foliar Residues (DFR) data was derived from a mancozeb study (MRID 

44959306) and an ETU study (MRID 44959603). While the application rates are the 

same for west and east cucurbit, the dislodgeable foliar residues for east and west are 

different. Since west DFR are higher, exposures and risks were estimated for “west” only. 

Post application non-cancer risks estimates from mancozeb-derived ETU were assessed

on Day 0 (the day of application). 

Golfers

Adults and children may be exposed to mancozeb-derived ETU through dermal contact with golf 

course turf treated directly with mancozeb. The scenarios, routes of exposure and lifestages 

assessed include:
Mancozeb Human Health Risk Assessment DP Nos. 411742 and 411764

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Golfing: adults (females 13-49 years old) (dermal); adults (males, females >49 years old)

(dermal); children 11 < 16 years old, except for females ≥ 13 years old (dermal); and 

children 6 < 11 years old (dermal).

The assumptions for the residential golfer assessment are refined as follows: 

• Golfer assessment is based on a maximum application rate of 17.4 lb ai/A (registered 

label EPA Reg No. 62719-402).

• Golfers have been assessed using a transfer coefficient of 5,300 cm2/hour (derived from 

a golf course worker exposure study, MRID 46734001). It is assumed golfers wear Tshirt and shorts.

• For golfer non-cancer and cancer risk assessment it was assumed that the tees, greens and 

fairways are treated and that the exposure time per day would be four hours.

• Measured Turf Transferable Residues (TTR) values based on a chemical specific 

(mancozeb) turf study (MRID 44958501).

◦ For golfer non-cancer risk assessment the highest measured residues from the turf 

study were used: mancozeb initial TTR of 0.20 (ug/cm2); ETU initial TTR of 

0.003 (ug/cm2). 

◦ For golfer cancer risk assessment the average highest TTR values (NC, PA, and 

CA sites) for Mancozeb and ETU residues from the turf study were used: 

mancozeb TTR of 0.15 (ug/cm2); ETU TTR of 0.003 (ug/cm2). 

• For cancer risk assessment, the exposure days per year for golfers (one day per year) is 

assumed to be one based upon the following:

◦ Golfers play an average of 19 rounds per year based upon information from the 

National Golf Foundation for the years 1994 through 2003. 

◦ According to BEAD, 20% percent of golf courses in the U.S. use mancozeb.

◦ According to the Golf Course Superintendent’s Association, fungicides are 

applied to golf courses an average of 6 times per year.

Residential Post-application Non-Cancer Exposure and Risk Equations

The algorithms used to estimate residential post-application exposure and dose can be found in 

the 2012 Residential SOPs (http://www.epa.gov/pesticides/science/residential-exposuresop.html) and in Appendix A of D411769.
Mancozeb Human Health Risk Assessment DP Nos. 411742 and 411764

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6.2.1 Home Garden Post-application Scenarios

Summary of Non-Cancer Exposure and Risk Estimates for ETU from Mancozeb for Home 

Gardeners

Table 6.2.1.1 below summarizes the post-application non-cancer risks estimates from mancozebderived ETU for adults and youth exposed to treated home gardens on Day 0 (the day of 

application). Exposures are shown for the commodity that might be found in a home garden and 

led to the highest exposure (i.e., cucurbit vegetables). The short-term dermal MOEs for all 

subpopulations on Day 0 exceed the LOCs (i.e., MOE ≥ 1000 for adult females 13-49 years old 

and MOE ≥ 100 for youth and other adults (males, females >49 years old)) and are therefore not 

of concern. 

Table 6.2.1.1 Mancozeb-derived ETU Post-application Short-Term (Non- Cancer) Exposure and Risk Estimates for 

Adult and Youth Home Gardeners 1

Lifestage LOC Crop 

Group

Application 

Rate 

(lb ai/acre)

Initial DFR 

(ug/cm2)

2

TC

(cm2/

hr)

ETU 

Foliar 

Dose 

(mg/kg/day)

Mancozeb 

Metabolized 

Dose to ETU

(mg/kg/day)

Total 

Absorbed 

Dermal 

Dose 

(mg/kg/day)

MOE

Mancozeb ETU 

Adult 

(Female 

13-49 

years old)

1000

Vegetable

cucurbit –

West 2

2.4 6.77 0.01

8,400 0.0007 0.0012 0.0019 2,700

Adult 

(males, 

females 

>49 years 

old)

100 8,400 0.0006 0.0010 0.0016 4,300

6 to 11 

yrs old 100 4,600 0.0004 0.0008 0.0012 5,800

11 to <16 

years

(except 

females 

13-16 

years old)

100 8,400 0.000843 0.001419 0.002262 3,100

1 Exposures are shown for high contact activities for the commodity that might be found in a home garden and led to the highest 

exposure.

2 Note – while the application rates are the same for west and east cucurbit, the dislodgeable foliar residues for east and west are 

different. Since west DFR are higher, exposures and risks were estimated for “west” only. Mancozeb study: MRID 44959306. 

ETU study: MRID 44959603
Mancozeb Human Health Risk Assessment DP Nos. 411742 and 411764

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Summary of Cancer Exposure and Risk Estimates for ETU from Mancozeb for Home Gardeners

Post- application cancer risks estimates from mancozeb-derived ETU for adults exposed to 

treated home gardens on Day 0 (the day of application) are summarized in Table 6.2.1.2, below. 

As in the table above, only the scenario with the highest anticipated exposure was assessed. 

Post-application cancer risks for adult home gardeners are estimated at 9 x 10-7.

Table 6.2.1.2 Mancozeb-derived ETU Post-application Cancer Exposure and Risk Estimates for Adult 

Gardeners on Day 0 Assuming Five Exposure Days per Year Over a Lifetime

Crop Group

Application 

Rate (lb 

ai/acre)1

Dose

Cancer Risk 5

Total Absorbed 

Dermal Dose 3

(mg/kg/day) 

Lifetime Average Daily Dose 

(LADD) 4, (mg/kg/day)

Vegetable, 

cucurbit –

(West)

2.4 20.0019 1.41 x 10-59 x 10-7

1 Exposures are shown for high contact activities for the commodity that might be found in a home garden and led to the highest 

exposure.

2 Note – while the application rates are the same for west and east cucurbit, the dislodgeable foliar residues for east and west are 

different. Since west DFR are higher, exposures and risks were estimated for “west” only. Mancozeb study: MRID 44959306. 

ETU study: MRID 44959603

3ADD = Absorbed Daily Dose from foliar an metabolized sources of ETU exposure

4 LADD = Lifetime Average Daily Dose = ADD * (5 exposure days per year/365 days per year)*(50 years 

 of exposure/78 years of life)

5 Risk = (LADD * Q1*), where Q1* = 0.0601 (mg/kg/day)-

6.2.2 Treated Turf Post-application Scenarios

Summary of Non-Cancer Exposure and Risk Estimates for ETU from Mancozeb for Golfers

The MOEs for short-term dermal risk for young golfers (<16 years old) and adult golfers, 

including females 13-49 years old, exposed to ETU from contact with mancozeb treated golf 

courses are above the LOCs (100 for youth and adults, other than females 13-49 years old, and 

1000 for females 13-49 years old) and are therefore, not of concern. A summary of exposure and 

risk estimates for adults and children exposed to ETU from contact with mancozeb treated golf 

courses is summarized in Table 6.2.2.1.

Summary of Cancer Exposure and Risk Estimates for ETU from Mancozeb for Golfers

The cancer risk to adult golfers from exposure to mancozeb-derived ETU is estimated to be 3 x 

10-8(Table 6.2.2.2).
Mancozeb Human Health Risk Assessment DP Nos. 411742 and 411764

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Table 6.2.2.1 Mancozeb-derived ETU Post-application Short-term (Non-cancer) Exposure and Risks Estimates for Golfers 

Lifestage LOC

Application 

Rate 2

(lb ai/acre)

Mancozeb 

TTR 

(ug/cm2)

ETU 

TTR

(ug/cm2)

Transfer 

Coefficient 3

(cm2/hr)

Hours 

per Day 

Exposure

Mancozeb 

Dermal Dose 4

(mg/kg/day)

Mancozeb 

Metabolized 

to ETU Dose 5

(mg/kg/day)

ETU Foliar 

Dose 6

(mg/kg/day)

Total ETU 

absorbed 

Dose 7

(mg/kg/day)

ETU 

Dermal 

MOE 8

Adult 

(Female

13-49 

years old)

1000

17.4 0.20 0.003

5,300 4. 0.000614 0.000046 0.000239 0.000286 17,500

11 to <16 

years

(except 

females 

13-16 

years old)

100 4,400 4 0.000618 0.000046 0.000240 0.000287 24,400

6 to <11 

years

100 2,900 4 0.000725 0.000054 0.000282 0.000337 20,700

Adult 

(males, 

females 

>49 years 

old)

100 5,300 4 0.000529 0.000040 0.000206 0.000246 28,000

1. Based on Mancozeb initial TTR of 0.20 (ug/cm2) and ETU initial TTR of 0.003 (ug/cm2). Highest residue values from turf study: MRID 449585-01.

2. Based on registered label EPA Reg No. 62719-402.

3. Transfer Coefficient (TC) values based on ExpoSAC 2012 Residential SOPs: http://www.epa.gov/pesticides/science/residential-exposure-sop.html

4. Mancozeb Dermal Dose = [DFR (μg/cm2) × Transfer Coefficient × 0.001 mg/μg × 4 hrs/day × dermal absorption (%)] BW (kg)

5.Mancozeb Metabolized Dose to ETU= Mancozeb Dermal Dose × 0.075

6. ETU Foliar Dermal Dose = [DFR (μg/cm2) × Transfer Coefficient × 0.001 mg/μg × 4 hrs/day × dermal absorption (%)] BW (kg).

7. Total Dermal Dose = ETU Foliar Dermal Dose + ETU Metabolized Dose to ETU

8.Total MOE = NOAEL (mg/kg/day)/Total ETU Dose (mg/kg/day). ETU Short-Term Dermal NOAEL: 5 mg/kg/day (females 13-49); 7 mg/kg/day (males, females >49, and youth 

6 to <16 except females 13-49).
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 Table 6.2.2.2 Summary of ETU Post-application Cancer Risks for Adults Exposed to Turf

Activity

Application 

Rate 

(lb ai/acre)

Mancozeb 

TTR 1

(ug/cm2)

ETU TTR 

(ug/cm2)

Transfer 

Coefficient

(cm2/hr)

Hours per 

Day

Exposure

Days Per 

Year 

Exposure

Years of 

Exposure 

per 

Lifetime

ADD 2

Total ETU 

absorbed 

Dose

(mg/kg/day)

LADD 3

(mg/kg/day)

Cancer 

Risk 4

Golf 17.4 0.15 0.03 5,300 4.0 1 50 0.000237 4.1 x 10-72.5 x 10-8

1 Average highest TTR values (NC, PA, and CA sites) for Mancozeb and ETU residues from turf study: MRID 449585-01) 

2ADD = Absorbed Daily Dose from foliar an metabolized sources of ETU exposure

3 LADD = Lifetime Average Daily Dose = ADD * (1 exposure day per year/365 days per year)*(50 years 

 of exposure/78 years of life)

4 Risk = (LADD * Q1*), where Q1* = 0.0601 (mg/kg/day)-1

6.3 Residential Risk Estimates for Use in Aggregate Assessment

HED combines risk values resulting from separate exposure scenarios when it is likely they can occur simultaneously based on the use 

pattern and the behavior associated with the exposed population. For home garden scenarios a combined (dermal plus inhalation) 

residential exposure assessment for handlers was conducted for ETU exposures. The residential handler scenario identified for use in 

performing an aggregate exposure assessment for ETU was for adults treating home gardens with mancozeb formulations 

(mixing/loading/application) utilizing a backpack sprayer (ETU combined MOE=32,700). However, for parent mancozeb exposures, 

the only route of exposure for handlers was through the inhalation route (no dermal toxicity). The residential handler scenario 

identified for use in performing a mancozeb aggregate exposure assessment was for home gardeners applying mancozeb to vegetables 

utilizing a backpack sprayer (MOE=170,000). A summary of short-term residential handler exposure and risk estimates for mancozeb 

inhalation exposures and ETU combined exposures, for use in the aggregate assessment, is presented in Tables 6.3.1 and 6.3.2,

respectively.

For residential post-application, the gardening scenarios represent the most conservative exposure estimates and were used in the 

aggregate assessment. The gardening scenarios result in higher estimated exposure than the golfing scenarios and are therefore 

protective of any golfer risk. The only route of exposure for treated garden post-application scenarios is through the dermal route 

(inhalation exposures are not expected). Since mancozeb does not have dermal toxicity, only ETU exposures are assessed for 

gardeners. The residential post-application scenarios used in performing an aggregate exposure assessment were adult (females 13-49

yrs) and youth gardeners. A summary of short-term residential post-application exposure and risk estimates for ETU from mancozeb 

identified for use in performing short-term post-application aggregate exposure assessments is presented in Table 6.3.3. 
Mancozeb Human Health Risk Assessment DP Nos. 411742 and 411764

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The residential handler scenario identified for use in performing an aggregate cancer assessment 

was for home gardeners applying mancozeb to vegetables utilizing a backpack sprayer. For 

applicators using backpack sprayers the estimated cancer risk from mancozeb-derived ETU was 

7 x 10-8(Table 6.3.4). 

The residential post-application scenario identified for use in performing an aggregate cancer 

assessment was for adults exposed to treated home gardens. The cancer risk to adult gardeners

from exposure to mancozeb-derived ETU is estimated in 9 x 10-7(Table 6.3.5).

Table 6.3.1 Residential Exposures and Risks for the Mancozeb Short-Term Aggregate Assessment 

(Residential Handler/Garden Use)

Lifestage Handler Exposure Scenario Dose (mg/kg/day) LOC MOEs

Adult

(Female 13-49 

years old)

M/L/A

Backpack 

sprayer

Inhalation Home Garden Activities 0.000122 300 170,000

Adult (Male, 

female >49 years 

old)

M/L/A

Backpack 

sprayer

Inhalation Home Garden Activities 0.000105 30 200,000

Table 6.3.2 Residential Exposures and Risks for the ETU (from Mancozeb) Short-Term Aggregate 

Assessment (Residential Handler/Garden Use)

Lifestage Handler Exposure Scenario Dose (mg/kg/day) LOC MOEs

Adult

(Female 13-49 

years old)

M/L/A

Backpack 

sprayer

Combined

(Inhalation + 

Dermal)

Home Garden Activities 0.000153 1000 32,700

Adult (Male, 

female >49 years 

old)

M/L/A

Backpack 

sprayer

Combined

(Inhalation + 

Dermal)

Home Garden Activities 0.000132 100 37,900

Table 6.3.3 Residential Exposures and Risks for the ETU (from Mancozeb) Short-Term Aggregate 

Assessment (Post-Application Exposures/Garden Use)

Lifestage Post-application Exposure Scenario Dose (mg/kg/day) LOC MOEs

Adult

(Female 13-49 years 

old) Liquid

sprays

Dermal Home Garden 

Activities

0.0019 1000 2,700

Child 6 < 11 years old 0.0012 100 5,800

Child 11 < 16years old 0.00226 100 3,100
Mancozeb Human Health Risk Assessment DP Nos. 411742 and 411764

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Table 6.3.4 Residential Exposures and Risks for the ETU (from Mancozeb) Aggregate Cancer 

Assessment (Residential Handler /Garden Use). 

Crop or Target

Total Absorbed Dose

ADD

(mg/kg/day)

Total LADD 3

(mg/kg/day)3

Residential Handler

Cancer Risk Estimate4

Mixer/Loader/Applicator (Liquid concentrate – Backpack Sprayer)

Home Gardens

(Vegetables) 1.32 x 10 -4

1.16 x 10 -6- 7 x 10 -8

Table 6.3.5 Residential Exposures and Risks for the ETU (from Mancozeb) Aggregate Cancer 

Assessment (Post-Application Exposures/Garden Use)

Activity

ADD

Total ETU absorbed Dose

(mg/kg/day)

LADD (mg/kg/day) Cancer Risk 

Home Garden Activities 0.0019 1.41 x 10-59 x 10-7

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 mancozeb or its metabolite ETU at this time. 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 (FIFRA) 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, developing policies and 

procedures, to identifying the need for and, subsequently, the way to incorporate post-application 

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 mancozeb.

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 airblast application method employed for mancozeb. 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 (see the Agency’s Spray Drift website for more information2. The 

 

2 Available: http://www.epa.gov/opp00001/factsheets/spraydrift.htm 
Mancozeb Human Health Risk Assessment DP Nos. 411742 and 411764

Page 50 of 77

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 risk estimates associated with drift.

Furthermore, turf (golfer scenario) and home garden uses were quantitatively assessed as part of 

this risk assessment; risk estimates addressed in the golfer turf assessment provide a worst case 

estimate of potential exposure from spray drift. It is noted that the 17.4 lb ai/acre application rate 

for turf was modeled to estimate post-application residential exposures (i.e., adults and youth 6 

to 16 years old). As this rate is equal to or higher than the agricultural application rates, this 

scenario is protective of any exposure via spray drift from agricultural mancozeb applications.

7.0 Aggregate Exposure/Risk Characterization

In accordance with the FQPA, HED 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, HED considers both the route and 

duration of exposure.

Based on the existing and newly proposed uses of mancozeb, exposure to mancozeb and to 

mancozeb-derived ETU can occur both from dietary sources (food and water) and in residential 

settings. The mancozeb uses in home gardens may result in handler exposure for adults and 

post-application exposure to adults and youth working in the garden. The mancozeb golf course 

turf use may result in post-application exposure to adults and youth playing golf. 

Mancozeb’s potential for carcinogenicity is due to the formation of the metabolite ETU; 

therefore, aggregate cancer risks are calculated based on exposure to mancozeb-derived ETU, 

using the cancer potency factor for ETU. 

The aggregate risk assessments are intended to be representative of exposures that are likely to 

co-occur. For the purpose of this risk assessment, HED only aggregated scenarios that are likely 

co-occur. The lifestages selected for the aggregate assessments represent the population 

subgroups expected to be the most highly exposed for each scenario. For more information on 

the exposure scenarios selected for aggregate assessment, see Section 6.3 above.

Mancozeb

Residues of mancozeb per se are not expected in drinking water, so aggregate risk assessments 

for mancozeb are limited to combined food and residential pathways. Additionally, an endpoint 

was not selected for dermal risk assessment since there was no systemic toxicity observed at the 

highest dose tested in the dermal studies; therefore exposure from the dermal route is not 

included in the mancozeb aggregate risk assessments. 
Mancozeb Human Health Risk Assessment DP Nos. 411742 and 411764

Page 51 of 77

The following aggregate risk assessments were conducted for mancozeb per se to support the 

proposed new uses: 

Mancozeb Acute Aggregate, which considers acute exposure to mancozeb per se from 

food only.

Mancozeb Short -Term Home Garden Aggregate (Adult), which considers residential 

handler exposures (inhalation) to adult applicators combined with average food 

exposures.

Mancozeb Long-Term or Chronic (Non-Cancer) Aggregate, which considers chronic 

exposure to mancozeb per se from food only.

ETU

The following aggregate risk assessments were conducted for mancozeb-derived ETU to support 

the proposed new uses:

ETU Acute Aggregate, which considers acute exposure to mancozeb-derived ETU from 

food and water.

ETU Short-Term Home Garden Aggregate (Adult and Youth), which considers 1) 

handler exposures (inhalation and dermal) plus food and water exposures for adults and 

2) post-application exposures (dermal) plus food and water for adults and youth entering 

the garden after treatment.

ETU Long-Term or Chronic (Non Cancer) Aggregate, which considers exposure from 

food and water only.

ETU Cancer Aggregate, which combines 1) adult handler home garden exposures 

(dermal and inhalation) and chronic food and water and 2) adult post-application 

exposures (dermal) plus food and water exposures for gardening activities.

Summaries of the aggregate risk assessments can be found below in Sections 7.1 through 7.5.

7.1 Acute Aggregate Risk

HED has calculated the acute dietary risk for females 13-49 years of age in Section 5.4 of this 

risk assessment. Since food is the only source contributing to the acute aggregate risk 

assessment, the acute aggregate risk assessments for mancozeb and ETU are equivalent to the 

acute dietary risk assessments detailed in Section 5.4. HED has no concern for acute aggregate 

risks to females 13 – 49 yrs, the subgroup of concern, resulting from exposure to mancozeb or 

ETU from the existing and new uses of mancozeb.

7.2 Short-Term Aggregate Risk

The short-term aggregate assessment for mancozeb and ETU combined adult residential handler 

exposures and dietary (food only for mancozeb; food and water for ETU) exposures. There are 
Mancozeb Human Health Risk Assessment DP Nos. 411742 and 411764

Page 52 of 77

no short-term aggregate risk estimates of concern for adults applying mancozeb to gardens 

(Tables 7.2.1 and 7.2.2).

A short-term aggregate assessment was performed for ETU for adults (using females age 13-49 

yrs. old as the most highly exposed population) and children (using youth ages 11-<16 yrs. old as 

the most highly exposed population) entering treated gardens. The garden scenarios resulted in 

higher post-application exposures than the golfing scenarios; assessment of the garden scenario 

is protective of any post-application exposures to adult and youth golfers. Post-application 

exposures to ETU were combined with dietary (food and water) exposures. There are no shortterm aggregate risk estimates of concern for adults or youth entering treated gardens (Table 

7.2.3).

Table 7.2.1 Mancozeb Short-Term Aggregate Risk Calculations

(Residential Handler/ Home Garden Use)

Population

Short-Term Scenario

NOAEL 

mg/kg/day LOC1

Max 

Allowable 

Exposure2

mg/kg/day

Average 

Food 

Exposure 

mg/kg/day

Residential 

Exposure 

mg/kg/day3

Total 

Exposure 

mg/kg/day4

Aggregate 

MOE (food

and 

residential)5

Adult Male (and 

Females >49 yrs) 21 30 0.7 0.000107 0.000105 0.000212 99,000

Adult Female

(13-49 yrs) 21 300 0.07 0.000101 0.000122 0.000223 94,000

1 LOC = 3x inter-species UF, 10x intra-species UF, and for females (13-49 yrs) the 10x FQPA SF is retained.

2 Maximum Allowable Exposure (mg/kg/day) = NOAEL/LOC

3 Residential Exposure = Inhalation exposure (Section 6.3).

4 Total Exposure = Avg Food Exposure + Residential Exposure)

5 Aggregate MOE = [NOAEL / (Avg Food Exposure + Residential Exposure)]

Table 7.2.2 ETU (derived from mancozeb) Short-Term Aggregate Risk Calculations

(Residential Handler/ Home Garden Use)

Population

Short-Term Scenario

NOAEL 

mg/kg/day LOC1

Max 

Allowable 

Exposure2

mg/kg/day

Average 

Food and 

Water 

Exposure 

mg/kg/day

Residential 

Exposure 

mg/kg/day3

Total 

Exposure 

mg/kg/day4

Aggregate 

MOE (food, 

water, and 

residential)5

Adult Male (and 

Females >49 yrs) 7 100 0.07 0.000030 0.000132 0.000162 43,000

Adult Female 

(13-49 yrs) 5 1000 0.005 0.000028 0.000153 0.000181 28,000

1 LOC = 10x inter-species UF, 10x intra-species UF; and for females (13-49 yrs) the 10x FQPA SF is retained.

2 Maximum Allowable Exposure (mg/kg/day) = NOAEL/LOC

3 Residential Exposure = [Dermal exposure + Inhalation Exposure]. (Section 6.3).

4 Total Exposure = Avg Food & Water Exposure + Residential Exposure)

5

re + Residential Exposure)]
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Table 7.2.3 ETU (derived from mancozeb) Short-Term Aggregate Risk Calculations

(Residential Post-Application/ Home Garden Use)

Population

Short-Term Scenario

NOAEL 

mg/kg/day LOC1

Max 

Allowable 

Exposure2

mg/kg/day

Average

Food and 

Water 

Exposure 

mg/kg/day

Residential 

Exposure 

mg/kg/day3

Total 

Exposure 

mg/kg/day4

Aggregate 

MOE (food, 

water, and 

residential)5

Adult Female 

(13-49 yrs) 5 1000 0.005 0.000028 0.0019 0.001928 2600

Youth 

(11- <16 yrs) 7 100 0.07 0.000022 0.0022 0.002222 3200

1 LOC = 10x inter-species UF, 10x intra-species UF; and for females (13-49 yrs) the 10x FQPA SF is retained.

2 Maximum Allowable Exposure (mg/kg/day) = NOAEL/LOC

3 Residential Exposure = [Dermal exposure]. (Section 6.3).

4 Total Exposure = Avg Food & Water Exposure + Residential Exposure)

5

7.3 Intermediate-Term Aggregate Risk

There are no intermediate-term residential exposure scenarios for mancozeb or ETU, therefore 

an intermediate-term aggregate assessment is not performed.

7.4 Long-Term or Chronic Aggregate Risk

There are no long-term residential exposure scenarios for mancozeb and there is not likely to be 

residues of mancozeb in drinking water. Therefore, the long-term or chronic (non-cancer) 

aggregate risk for mancozeb includes contribution from dietary (food only) exposure alone. The 

chronic (non-cancer) aggregate risk assessment for mancozeb is equivalent to the mancozeb 

chronic dietary risk assessment conduction in Section 5.4 of this document. HED has no concern 

for chronic (non-cancer) aggregate risks to the general population or any regulated subgroup, 

resulting from exposure to mancozeb per se from the existing and new uses of mancozeb.

The long-term or chronic (non-cancer) aggregate risk for mancozeb-derived ETU includes 

contribution from dietary (food and water) exposure alone. The chronic (non-cancer) aggregate 

risk assessment for mancozeb-derived ETU is equivalent to the mancozeb-derived ETU chronic 

dietary risk assessment conduction in Section 5.4 of this document. HED has no concern for 

chronic (non-cancer) aggregate risks to the general population or any regulated subgroup, 

resulting from exposure to mancozeb-derived ETU from the existing and new uses of mancozeb.

7.5 Cancer Aggregate Risk

The cancer aggregate assessment for mancozeb-derived ETU includes contributions from 

residential and dietary (food and water) exposures and considers the scenarios resulting in the 

highest estimated exposures, which are applying mancozeb to gardens and entering treated 
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gardens. The cancer aggregate risk estimates (handler and post-application) for the U.S. 

population are 2 x 10-6and 3 x 10-6, respectively.

Table 7.5.1 ETU (derived from mancozeb) Aggregate Cancer Risk Estimates

(Residential Handler/Garden Use)

Population Cancer Slope 

Factor (Q1*)

Food and Water 

Exposure 

(mg/kg/day) 1

Residential 

Exposure 

(LADD)

(mg/kg/day)

2

Aggregate 

Cancer Risk 

(food, water, 

residential)3

U.S. Population 6.01 x 10 -23 x 10 -51.16 x 10 -62 x 10 -6

1 Dietary exposure: Table 5.4.6.2.

2 Residential exposure values used in aggregate assessment: Table 6.4.4.

3 Aggregate Cancer Risk = (Q1*) (Food & Water Exposure + LADD)

Table 7.5.2 ETU (derived from mancozeb) Aggregate Cancer Risk Estimates

(Post-Application / Garden Use)

Population Cancer Slope 

Factor (Q1*)

Food and Water 

Exposure 

(mg/kg/day) 1

Residential 

Exposure 

(LADD)

(mg/kg/day)

2

Aggregate 

Cancer Risk 

(food, water, 

residential)3

U.S. Population 6.01 x 10 -23 x 10 -51.41 x 10-53 x 10 -6

1 Dietary exposure: Table 5.4.6.2.

2 Residential exposure values used in aggregate assessment: Table 6.4.5.

3Aggregate Cancer Risk = (Q1*) (Food & Water Exposure + LADD)

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 mancozeb and any other substances. Mancozeb does produce a toxic metabolite, ETU, which 

is produced by other EBDC compounds. Risks from combined exposures to ETU from all 

EBDC compounds are addressed in a separate ETU aggregate risk assessment. For the purposes 

of this tolerance action EPA has not assumed that mancozeb 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

Mancozeb is a widely used contact fungicide in agriculture, professional turf management, 

horticulture, and home gardening. Mancozeb formulations include wettable powders, dry 

flowables, liquid flowables and dusts. The product is currently registered for foliar application 

and seed treatment on various agricultural crops. Horticultural uses include ornamental plants in 
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nurseries and greenhouses, sod farms, and golf courses. Occupational assessments are performed 

for the proposed U.S. walnut use. Occupational assessments are not performed for the proposed 

use on imported tangerines.

The petitioner has proposed to amend the use pattern for various mancozeb formulations (i.e., 

Penncozeb Technical [EPA Reg. No.70506-188]; Penncozeb 75DF [EPA Reg. No. 70506-185];

Penncozeb 4FL Plowable Fungicide [EPA Reg. No. 70506-194]; Manzate Pro-Stick Fungicide, 

[EPA Reg. No. 70506-234]; and Manzate Flowable [EPA Reg. No. 70506-236] adding a use on 

walnuts for the control of walnut blight, a bacterial disease caused by Xanthomonas campestris 

pv. juglandis.

The proposed use pattern and directions are similar for all mancozeb formulations for 

applications on walnuts. Ground and aerial foliar applications are permitted. The maximum 

single application rate proposed is 1.8 pounds mancozeb per acre. The labels propose a 

maximum of ten applications per year (i.e., maximum total application rate of 18 lb ai/year), and 

a Pre-Harvest Interval (PHI) of 75 days. Applications are to begin at early pre-bloom prior to or 

when catkins are partially expanded and additional applications can be made during bloom and 

early nutlet stage, or as needed if frequent rainfall occurs. 

9.1 Short- and Intermediate-Term and Cancer Handler Risk

Occupational handler exposure to mancozeb is expected for individuals involved in foliar 

applications to walnuts (i.e., during mixing, loading, and applying). Because ETU is an 

environmental degradate and metabolite of mancozeb, both mancozeb and ETU exposures have 

been assessed. Based on application rate and label information, handler exposure is expected to 

occur for short- and intermediate-term durations. Chronic exposure is not expected for the 

proposed use patterns. A cancer assessment is also performed for ETU as ETU has been 

classified as a Group B2 carcinogen. Only inhalation exposures were considered for mancozeb 

because no effects were observed at the limit dose in a 28-day dermal rat study. In the case of 

ETU, however, inhalation and dermal exposures were considered for both the non-cancer and 

cancer risk assessments.

ETU is produced through degradation of mancozeb during spray mix preparation, during spray 

application and in the environment (e.g., on treated leaves) after application. Tank mix stability 

studies submitted to, and reviewed by, the Agency in 1991 indicated that 0.1 percent of the 

mancozeb parent converted to ETU during mixing/loading and 0.2 percent converted to ETU 

during application (D327307 & D327318; D. Davis, 6/11/07). Post-application assessments 

were based on empirical measures of ETU in dislodgeable foliar residue dissipation studies. 

Approximately 7.5% of parent EBDC (mancozeb) is metabolized to ETU in the body. The ETU 

formed from the in vivo metabolism of parent EBDC is added to the ETU to which people are 

exposed as a degradate (direct exposure) to determine a total ETU absorbed dose.

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

risk assessments. See D411769, Mancozeb: Occupational and Residential Risk Assessment to 

Support Request for Section 3 Registrations on Walnuts for complete details regarding body 
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weight assumptions, absorption, unit exposures, area treated, exposure durations, and the 

associated calculations.

Based on the anticipated use patterns and current labeling, types of equipment and techniques 

that can potentially be used, occupational handler exposure is expected from the proposed walnut 

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

the following scenarios: 

1. Mixer/Loader using open pouring of liquids in support of aerial, and airblast 

operations; 

2. Mixer/Loader using dry flowable and water dispersible granules in support of 

aerial and airblast operations; 

3. Aerial Applicators (enclosed cockpit);

4. Applicators using airblast equipment; and

5. Mixer/loader/applicator with mechanically pressurized handgun.

Although flagger scenarios are normally considered for aerial application, they are not 

considered for mancozeb because the label prohibits the use of human flaggers. As stated on the 

labels, mixers, loaders and applicators must wear: coveralls, long sleeved shirt, long pants, 

chemical resistant gloves (waterproof material), socks, and shoes. Mixers and loaders must also 

wear chemical resistance aprons and protective eyewear. It should be noted that no respiratory 

protection equipment (e.g., respirators) is requested on the labels.

The level of concern (LOC) for mancozeb short- and intermediate-term occupational risk 

assessments is for MOEs below 30 for adult males and females (over 49 years of age), and for 

MOEs below 300 for females 13-49 years of age. The LOC for mancozeb-derived ETU shortand intermediate-term occupational risk assessments is for MOEs below 100 for adult males and 

females (over 49 years), and for MOEs below 1000 for females 13-49 years. 

Occupational Handlers Non-Cancer and Cancer Exposure and Risk Estimates for Mancozeb and 

ETU

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

All mixer/loader non-cancer risk scenarios do not exceed HED’s level of concern (i.e., MOEs ≥ 

300 for mancozeb exposures and MOEs ≥1000 for ETU exposures), at some level of risk 

mitigation (e.g., gloves, respirators, or other engineering control measures). Non-cancer risk 

estimates for M/L liquids in support of air and airblast applications ranged from MOE=10,500 

(females 13-49 years old) to MOE=106,600 (males and females >49 years old) at label PPE (i.e.,

gloves, no respirator). However, non-cancer risks estimates for M/L scenarios using dry flowable 

(DF) formulations in support of aerial applications to walnuts exceed HED’s level of concern for 

females age 13-49 years (i.e., MOE=260 for mancozeb inhalation exposures and MOE=750 for 
Mancozeb Human Health Risk Assessment DP Nos. 411742 and 411764

Page 57 of 77

ETU exposures) at label PPE. It should be noted that no respiratory protection equipment or 

other engineering control measures are requested on the DF labels. With the addition of a 

respirator, MOE=1300 for mancozeb inhalation exposures and MOE=2900 for ETU exposures 

for females 13-49 mixing and loading the DF formulation for aerial application to walnuts.

Likewise, all application non-cancer risk scenarios do not exceed HED’s level of concern at 

some level of risk mitigation (e.g., gloves or other engineering control measures). Aerial and 

airblast applicator risks do not exceed HED’s level of concern (i.e., MOEs ≥ 300 for mancozeb 

exposures and MOEs ≥1000 for ETU exposures) with engineering control (i.e., enclosed cockpit 

or closed cab). Mixer/loader/ applicators with mechanically pressurized handgun risks do not 

exceed HED’s level of concern at label PPE (i.e., gloves, no respirator). The handler risks 

estimates (i.e., non-cancer) for mixing/loading (M/L) and application scenarios of the proposed 

mancozeb formulations on walnuts are presented on Tables 9.1.1 and 9.1.2. 
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Table 9.1.1 Short-/Intermediate-Term Occupational Non-Cancer Exposure and Risk Estimates for Mancozeb. All estimates are at 

baseline mitigation (i.e., without respirator, unless specified). 

Exposure Scenario 6 Crop or Target LOC

Inhalation Unit Exposure 

(ug/lb ai)1 Maximum

Application Rate2

Area Treated or 

Amount Handled 

Daily3

Inhalation

Mitigation Level Dose (mg/kg/day)4 MOE5

Mixer/Loader (Adult Males, Females >49 years)

M/L, DF/WDG, Aerial, Broadcast

Walnuts 30

8.96

1.8 lb ai/acre

350 acres

0.070560 300

0.014112

(PF5 Respirator)7 1,500

M/L, DF/WDG, Airblast, Broadcast 40 acres 0.008064 2,600

M/L, L/SC Aerial, Broadcast

0.219

350 acres 0.001725 12,200

M/L, L/SC Airblast, Broadcast 40 acres 0.000197 106,600

Mixer/Loader (Females 13-49 years)

M/L, DF/WDG, Aerial, Broadcast

Walnuts 300

8.96

1.8 lb ai/acre

350 acres

0.081808 260

0.016361

(PF5 Respirator) 1,300

M/L, DF/WDG, Airblast, Broadcast 40 acres 0.009349 2,200

M/L, L/SC, Aerial, Broadcast

0.219

350 acres 0.002000 10,500

M/L, L/SC; Airblast, Broadcast 40 acres 0.000228 92,000

Applicator (Adult Males, Females >49 years)

Applicator, Spray, Aerial, Broadcast

Walnuts 30

0.068

(Engineering Control)

1.8 lb ai/acre

350 acres 0.000536 39,200

Applicator, Spray, Airblast, Broadcast

(Open Cab) 4.71 40 acres 0.004239 5,000

Applicator, Spray, Airblast, Broadcast

(Closed Cab)

0.068

(Engineering Control) 40 acres 0.000061 343,100

Applicator (Females 13-49 years)

Applicator, Spray, Aerial, Broadcast Walnuts 300

0.068

(Engineering Control) 1.8 lb ai/acre 350 acres 0.000621 33,800
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Table 9.1.1 Short-/Intermediate-Term Occupational Non-Cancer Exposure and Risk Estimates for Mancozeb. All estimates are at 

baseline mitigation (i.e., without respirator, unless specified). 

Exposure Scenario 6 Crop or Target LOC

Inhalation Unit Exposure 

(ug/lb ai)1 Maximum

Application Rate2

Area Treated or 

Amount Handled 

Daily3

Inhalation

Mitigation Level Dose (mg/kg/day)4 MOE5

Applicator, Spray, Airblast, Broadcast

(Open Cab) 4.71 40 acres 0.004914 4,300

Applicator, Spray, Airblast, Broadcast

(Closed Cab)

0.068

(Engineering Control) 40 acres 0.000070 297,000

Mixer/Loader/Applicator (Adult Males, Females >49 years)

M/L/A, DF/WDG, Mechanicallypressurized Handgun, Broadcast Walnuts 30 3.9 0.018 lb ai/gallon 1000 gallons 0.000878 23,930

Mixer/Loader/Applicator (Females 13-49 years)

M/L/A, L/DF/WDG, Mechanicallypressurized Handgun, Broadcast Walnuts 300 3.9 0.018 lb ai/gallon 1000 gallons 0.001017 20,600

1 Based on “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” ([March 2012]); includes data from PHED/ORETF/AHETF (level of mitigation: Baseline, 

PPE, Eng. Controls).

2 Based on registered labels (Reg. No. 70506-185, 70506-194, 70506-234, 70506-236).

3 Exposure Science Advisory Council Policy #9.1.

4

Inhalation 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 Daily (A or 

gal/day) /BW (kg).

5

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

6 WDG- Water Dispersible Granules; DF- Dry Flowable; L/SC– Liquid/Soluble Concentrate

7

PF5 Respirator is a respirator with a protection factor of 5 (i.e., it provides 80 percent inhalation protection).
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Table 9.1.2 Short-/Intermediate -Term Occupational Non-Cancer Exposure and Risk Estimates for ETU. All estimates are at label 

PPE (i.e., gloves, no respirator, unless specified. 

Exposure Scenario Crop or Target

Dermal Unit 

Exposure 

(ug/lb ai)1

Inhalation Unit 

Exposure 

(ug/lb ai)1

Maximum 

Application 

Rate2

Area Treated 

or Amount 

Handled 

Daily3

ETU Dermal Dose

(mg/kg/day) 6

ETU Inhalation Dose

(mg/kg/day) 6

Total ETU 

Dose 

(mg/kg/day)7

Total 

MOE8

Mitigation 

Level

Mitigation 

Level

ETU from 

Direct 

Exposure 

(Present in

Tank Mix ) 4

ETU 

Metabolized 

from 

Mancozeb5

ETU from 

Direct 

Exposure 

(Present in

Tank Mix ) 4

ETU 

Metabolized 

from 

Mancozeb5

Mixer/Loader (Females 13-49 years)

M/L, DF/WDG, Aerial, 

Broadcast

Walnuts

51.6 8.96

1.8 lb ai/acre

350 acres

0.000122 0.000353 0.000081 0.006135 0.006693 750

0.000122 0.000353

0.000001

(PF5 

Respirator)

0.001243

(PF5 

Respirator)

0.001719

(PF5 

Respirator)

2,900

M/L, DF/WDG, Airblast, 

Broadcast 40 acres 0.000014 0.000040 0.000009 0.000701 0.000764 6500

M/L, L/SC/EC, Aerial, 

Broadcast

37.6 0.219

350 acres 0.000089 0.000029 0.000002 0.000049 0.000498 10,000

M/L, L/SC/EC, Airblast, 

Broadcast 40 acres 0.000010 0.000029 0.000000 0.000017 0.000056 87,700

Applicator (Females 13-49 years)

Applicator, Spray, Aerial, 

Broadcast

Walnuts

5.0

(Engineering 

Control)

0.068

(Engineering 

Control)

1.8 lb ai/acre

350 acres 0.000023 0.000034 0.000001 0.000046 0.000105 47,300

Applicator, Spray, 

Airblast, Broadcast (Open 

Cab)

1,590 4.71 40 acres 0.000863 0.001244 0.000009 0.000369 0.002486 2,000

Applicator, Spray, 

Airblast, Broadcast

(Closed Cab)

14.6

0.068

(Engineering 

Control)

40 acres 0.000008 0.000011 0.0000001 0.000005 0.000025 202,000

Mixer/Loader/Applicator (Females 13-49 years)

M/L/A, L/DF/WDG, 

Mechanically-pressurized 

Handgun, Broadcast

Walnuts 390 3.9 0.0180 lb 

ai/gallon 1000 gallons 0.000053 0.000076 0.000002 0.000076 0.000208 24,100

1

PHED (level of mitigation: Baseline, PPE, Eng. Controls).
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2 Based on registered labels (Reg. No. 70506-185, 70506-194, 70506-234, 70506-236).

3 Exposure Science Advisory Council Policy #9.1.

 Daily Exposure = 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) x DAF (%)

4

.ETU Average Daily Dose from Direct Exposure to ETU (mg/kg/day) = [Daily Exposure (mg ai/day) * Absorption (%)]/ BW (kg) 

 Absorption =0.1 (for mixing and loading) or 0.2 (for application) % of mancozeb.

5 ETU Average Daily Dose From metabolic conversion of mancozeb (mg/kg/day) = [Daily Exposure (mg ai/day) * Absorption (%)*Metabolic ETU Conversion]/ BW (kg)

 7.5 percent of the absorbed mancozeb dose is metabolically converted to ETU

6 Dermal or Inhalation Dose= ETU Average Daily Dose from Direct Exposure to ETU (mg/kg/day) + ETU Average Daily Dose From metabolic conversion of mancozeb (mg/kg/day) 

7

Total ETU Dose = Total Dermal ETU Dose (mg/kg/day) + Total Inhalation ETU Dose (mg/kg/day)

8Total MOE = NOAEL (mg/kg/day)/Total ETU Dose (mg/kg/day). ETU Short/ Intermediate-Term Dermal and Inhalation NOAEL= 5 mg/kg/day. LOC=1000
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Summary of Occupational Handler Cancer Exposure and Risk Estimates

The cancer risks for all mixing/loading (M/L) scenarios for private handlers are estimated in the 

10-6to 10-8range at label PPE (i.e., gloves, no respirator). Cancer risks for both private and 

commercial handlers M/L liquids in support of air and airblast applications ranged from 9.5 x10-7

to 3.6 x10-8at label PPE. Cancer risks for commercial handlers M/L scenarios using dry flowable 

(DF) formulations in support of aerial applications ranged from 1.3 x10-5at label specified PPE, 

to 4.9 x10-7 with the use of water soluble bags (WSB) as an engineering control measure. Cancer 

risks for commercial handlers M/L scenarios using DF formulations in support of airblast 

applications ranged from 1.5 x10-6at label PPE, to 3.8 x10-7 with additional PPE (i.e., PF5 

respirator). Cancer risks for private handlers mixing/loading DF formulations in support of aerial 

applications ranged from 4.3 x10-6at label PPE, to 7.0 x10-7 with additional PPE (i.e., PF10 

respirator). Cancer risks for private handlers mixing/loading DF formulations in support of 

airblast applications were estimated at 4.9 x10-7at label PPE.

The cancer risks for all application scenarios are estimated in the 10-6(open cab airblast 

applications) to 10-8 range for both private and commercial handlers (closed cab or cockpit for 

airblast and aerial applications, respectively) The cancer risks for mixing/loading/application 

(M/L/A) scenarios are estimated in the 10-7range for both private and commercial handlers at 

label PPE.

A summary of occupational handler cancer risks for applying mancozeb for the proposed uses is 

presented on Table 9.1.3.
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Table 9.1.3 Occupational Cancer Exposure and Risk Estimates for ETU from Mancozeb. 

All estimates are at label PPE (i.e. gloves, no respirator) unless specified. 

Crop or Target Exposure 

Scenario

Handler Dermal 

ADD1

(mg/kg/day)

Handler 

Inhalation ADD2 

(mg/kg/day)

Total LADDc

Cancer

Private Handler Commercial Handler Private Handler Commercial Handler

LADD3

(mg/kg/day) LADD (mg/kg/day) 3 Mitigation 

Level

Risk 

Estimate4

Mitigation 

Level

Risk 

Estimate4

Mixer/Loader

Walnuts

M/L, DF/WDG, 

Aerial, Broadcast

0.000476 0.006217 7.09 x 10-52.13 x 10-4 Gloves 4.3 x 10-6 Gloves 1.3 x 10-5

0.000476 0.001243 1.82 x 10-55.47 x 10-5 Gloves, 

PF 5 R5 1.1x 10-6 Gloves, PF 5 R5 3.3 x 10-6

0.000476 0.000622 1.16 x 10-53.49 x 10-5 Gloves, 

PF 10 R 7.0 x 10-7 Gloves, PF 10 R 2.1 x 10-6

0.000090 0.000167 NA 8.17 x 10-6

WSB 6

(Engineering 

Control)

NA

WSB 6

(Engineering 

Control)

4.9 x 10-7

M/L, DF/WDG, 

Airblast, 

Broadcast

0.000054 0.000711 8.11 x 10-62.43 x 10-5 Gloves 4.9 x 10-7 Gloves 1.5 x 10-6

0.000054 0.000142 NA 6.25 x 10-6 Gloves, 

PF 5 R5 NA Gloves, PF 5 R5 3.8 x 10-7

M/L, L/SC/EC, 

Aerial, Broadcast 0.000347 0.000152 5.28 x 10-6

1.59 x 10-5 Gloves 3.2 x 10-7 Gloves 9.5 x 10-7

M/L, L/SC/EC, 

Airblast, 

Broadcast

0.000040 0.000017 1.04 x 10-71.81 x 10-6 Gloves 3.6 x 10-8 Gloves 1.1 x 10-7

Applicator

Walnuts

Applicator, 

Spray, Aerial, 

Broadcast

0.000058 0.000048 1,12 x 10-63.37 x 10-6 Closed 

Cockpit 6.5 x 10-8 Closed Cockpit 2.0 x 10-7

Applicator, 

Spray, Airblast, 

Broadcast (Open 

Cab)

0.002107 0.000378 2.63 x 10-57.91 x 10-5 Open Cab/No 

respirator 1.6 x 10-6 Open Cab/No respirator 4.8 x 10-6

0.000019 0.000076 2.31 x 10-56.94 x 10-5 Open Cab/ 

PF 5 R 1.4 x 10-6 Open Cab/ PF 5 R 4.2 x 10-6

Applicator, 

Spray, Airblast, 0.000019 0.000005 2.63 x 10-7

7.89 x 10-7 Closed Cab 1.6 x 10-8 Closed Cab 4.7 x 10-8
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Table 9.1.3 Occupational Cancer Exposure and Risk Estimates for ETU from Mancozeb. 

All estimates are at label PPE (i.e. gloves, no respirator) unless specified. 

Crop or Target Exposure 

Scenario

Handler Dermal 

ADD1

(mg/kg/day)

Handler 

Inhalation ADD2 

(mg/kg/day)

Total LADDc

Cancer

Private Handler Commercial Handler Private Handler Commercial Handler

LADD3

(mg/kg/day) LADD (mg/kg/day) 3 Mitigation 

Level

Risk 

Estimate4

Mitigation 

Level

Risk 

Estimate4

Broadcast 

(Closed Cab)

Mixer/Loader/Applicator

Walnuts

M/L/A, 

L/DF/WDG, 

Mechanicallypressurized 

Handgun, 

Broadcast

0.000129 0.000078 2.2 x 10-66.6 x 10-6 Gloves 1.3 x 10-7 Gloves 4.0 x 10-7

1 Dermal ADD = Dermal Absorbed Daily Dose 

2

Inhalation ADD = Inhalation Absorbed Daily Dose 

3 Total LADD = total absorbed dose [Dermal dose + Inhalation Dose] * Days per year of exposure * Years per lifetime of exposure / (365 days/year x Lifetime expectancy).

4 Cancer risk estimates = LADD * Q1*

, where Q1

*

= 6.01 x 10 -2(mg/kg/day)

-1

.

5

. PF5 Respirator: is a respirator with a protection factor of 5

6

. WSB Water soluble bags (engineering control)
Mancozeb Human Health Risk Assessment DP Nos. 411742 and 411764

Page 65 of 77

9.2 Short- and Intermediate-Term and Cancer Post-Application Risk

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.

9.2.1 Dermal Post-Application Risk

Occupational re-entry workers may experience short-/intermediate-term exposure to mancozeb

while performing activities after application to walnuts. ETU can also be found as an 

environmental degradate in post-application monitoring studies on agricultural crops and turf so 

the Agency has also evaluated direct exposures of ETU to post-application workers as 

appropriate. Finally, ETU can be formed in the human body via various metabolic pathways after 

mancozeb is absorbed. The contributions of this metabolic conversion are also considered in the 

assessment for ETU.

Eight dislodgeable foliar residue (DFR) studies were submitted in support of reregistration of 

mancozeb and these were reviewed in Mancozeb ORE Assessment for the RED (D317368, T. 

Dole, 05/31/05). The DFR studies were conducted on apples, grapes, and tomatoes using airblast 

and groundboom application of Dithane DF dry flowable fungicide. The DFR study selected for 

estimating post-application exposure on walnuts is MRID 44959602 (Airblast on WA Apple).

This study monitored for both mancozeb residues and ETU residues.

Since there is no dermal endpoint identified for mancozeb, only dermal post-application 

assessment for its degradate ETU has been conducted. Post-application non-cancer (short- and 

intermediate-term) exposures and cancer exposures are assessed for ETU. The level of concern 

for the ETU post-application occupational risk assessment is for MOEs below 1000. The ETU 

exposure was calculated by adding the ETU dose absorbed from the leaf surface (direct contact) 

to the ETU that is metabolically converted from absorbed mancozeb. 

See D411769 Mancozeb: Occupational and Residential Risk Assessment to Support Request for 

Section 3 Registrations on Walnuts for complete details regarding body weight assumptions, 

absorption, unit exposures, exposure durations, and the associated calculations. Additional 

information regarding the residue studies used in this assessment may also be found in D411769.

Occupational Post-application Non-Cancer Dermal Risk Estimates

All post-application occupational exposure scenarios assessed resulted in MOEs that do not 

exceed HED's level of concern (i.e., ETU MOEs ≥ 1000) at mancozeb current Restricted Entry 
Mancozeb Human Health Risk Assessment DP Nos. 411742 and 411764

Page 66 of 77

Interval (REI) of 24 hours which is also proposed for walnut crops. Post-application 

occupational non-cancer risks estimates are summarized in Table 9.2.1.1.

Table 9.2.1.1 Summary of Occupational/Commercial ST/IT Post-application Non-Cancer 

Risk Estimates for ETU from Mancozeb 1

Crop/Site Activities Transfer Coefficient 

(cm2/hr)

ETU Foliar 

Dose 2

(mg/kg/day)

Mancozeb 

Metabolized 

Dose to ETU 3

(mg/kg/day)

Total Dermal 

Dose 4

(mg/kg/day)

MOE5

Short-term /Intermediate-term

Walnuts

Orchard maintenance 100 0.000056 0.000050 0.000106 47,000

Scouting 580 0.000325 0.000290 0.000611 8,100

Weeding, Hand 100 0.000056 0.000050 0.000106 47,000

Transplanting 230 0.000129 0.000115 0.000244 20,500

Harvesting (mechanical 

shaking) 190 0.000107 0.000095 0.000202 24,800

1. Based on Mancozeb initial DFR of 16.5(ug/cm2) and ETU initial DFR of 0.053 (ug/cm2). Values from MRID 449596-02 (WA Airblast Apple)

2. ETU Foliar Dermal Dose = [DFR (μg/cm2) × Transfer Coefficient × 0.001 mg/μg × 8 hrs/day × dermal absorption (%)] BW (kg).

3. Mancozeb Dermal Dose = [DFR (μg/cm2) × Transfer Coefficient × 0.001 mg/μg × 8 hrs/day × dermal absorption (%)] BW (kg)

 ETU Metabolized Dose to ETU= Mancozeb Dermal Dose × 0.075

4. Total Dermal Dose = ETU Foliar Dermal Dose + ETU Metabolized Dose to ETU

5. MOE = POD (mg/kg/day) / Daily Dermal Dose. LOC= 1000

Restricted Entry Interval

Mancozeb is classified as Toxicity Category IV via the dermal route and Toxicity Category IV 

for skin irritation potential. Mancozeb is not a skin sensitizer. Mancozeb’s degradate; ETU is 

not acutely toxic via the dermal or inhalation routes of exposure. ETU is not a skin or eye 

irritant. The interim 24-hour restricted re-entry interval (REI) on the proposed label is in 

compliance with the Worker Protection Standard (WPS) for agricultural pesticides and is 

consistent with previously approved REIs for registered formulations of mancozeb. Short- and 

intermediate-term post-application risk estimates were not a concern on day 1 (24 hours 

following application) for all post-application activities.

Occupational Post-application Cancer Dermal Risk Estimates

The ETU cancer risk estimates for walnut post-application worker scenarios assessed are in the 

10-7to 10-8range for private growers and 10-6to 10-7for commercial growers at Day 1 (i.e., at 

the 24 hour REI). Post-application occupational cancer risks estimates are summarized in Table 

9.2.1.2.

Table 9.2.1.2 Occupational Post-Application Cancer Exposures and Risk Estimates for ETU from Mancozeb

Crop 

Grouping/Crop Activity Days After Treatment

Dermal LADD

(mg/kg/day)1 Cancer Risk Estimate2

Private 

Grower

Commercial 

Grower

Private 

Grower

Commercial 

Grower

Trees, Nut, 

Crop Group 14

(Walnuts)

Orchard maintenance 1 0.00000112 0.00000337 6.8 x 10-82.0 x 10-7

Scouting 1 0.00000652 0.00001957 3.9 x 10-71.2 x 10-6

6 0.00000567 0.00001700 3.4 x 10-71.0 x 10-6
Mancozeb Human Health Risk Assessment DP Nos. 411742 and 411764

Page 67 of 77

Table 9.2.1.2 Occupational Post-Application Cancer Exposures and Risk Estimates for ETU from Mancozeb

Crop 

Grouping/Crop Activity Days After Treatment

Dermal LADD

(mg/kg/day)1 Cancer Risk Estimate2

Private 

Grower

Commercial 

Grower

Private 

Grower

Commercial 

Grower

Weeding, Hand 1 0.00000112 0.00000337 6.8 x 10-8

2.0 x 10-7

Transplanting 1 0.00000258 0.00000776 1.6 x 10-7

4.7 x 10-7

Harvesting (mechanical 

shaking) 1 0.00000213 0.00000641 1.3 x 10-7

3.9 x 10-7

1 Dermal LADD = Dermal dose * Day per year of exposure x Years per lifetime of exposure / (365 days/year x Lifetime 

expectancy).

2 Cancer risk estimates = LADD * Q1*

, where Q1

*

= 6.01 x 10 -2(mg/kg/day)-1

9.2.2 Inhalation Postapplication Risk

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

assessment was not performed for mancozeb or for its degradate, ETU, at this time primarily 

because of the low acute inhalation toxicity (Toxicity Category IV). However, there are multiple 

potential sources of post-application inhalation exposure to individuals performing postapplication 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 Federal 

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

and received the SAP’s final report on March 2, 20103.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 post-application 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 mancozeb.

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. The airblast application handler scenario4is 

believed to represent a reasonable worst-case surrogate estimate of post-application inhalation 

exposure during typical post-application activities on nut crops (e.g., mechanical harvesting 

activities). The use of the handler scenario of airblast application for translation to the inhalation 

exposure of harvesting is a very conservative assumption. It is assuming harvesting inhalation 

exposure to be the same as on the last day of treatment. Furthermore, it should be noted that the 

labels specify a pre-harvest interval of 75 days. Hence, some dissipation of mancozeb residue 

 

3 Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html

4

See Tables 9.1.1 to 9.2.1.2 for a description of non-cancer and cancer risk estimates for commercial and private 

grower applications of mancozeb on walnut crops.
Mancozeb Human Health Risk Assessment DP Nos. 411742 and 411764

Page 68 of 77

can be assumed to occur by the harvesting day through chemical degradation or environmental 

dissipation. Therefore, it is expected that these handler inhalation exposure estimates would be 

protective of most occupational post-application inhalation exposure scenarios.

10.0 References

P. Savoia, 4/8/13, D404217, Mancozeb. Section 3 Registration for Establishing a Tolerance on 

Imported Tangerines. Summary of Analytical Chemistry and Residue Data. 

P. Savoia, 4/8/13, D402042, Mancozeb. Section 3 Registration Adding the Use of Mancozeb on 

Walnuts. Summary of Analytical Chemistry and Residue Data. 

P. Savoia, 4/8/13, D402043 and D405277, Mancozeb.Acute, Chronic, and Cancer Dietary 

Exposure Assessments of Food and Drinking Water to Support the New Use of Mancozeb on 

Walnuts and the Establishment of a Tolerance on Imported Tangerines for Section 3 

Registration. 

A. Rivera-Lupiáñez, 5/14/13, D411769, Mancozeb: Occupational and Residential Risk 

Assessment to Support Request for Section 3 Registrations on Walnuts.

M. Ruhman, 7/3/12, D397306, Estimated Drinking Water Concentrations of ETU Degradate 

(Ethylene-thio-urea degradate) of Mancozeb from its Proposed New Use on Walnuts for Use in 

Human Health Risk Assessment.

D. Davis, 6/11/07, D327307 & D327318, Mancozeb: Human Health Risk Assessment to 

Support Proposed New Uses on Broccoli, Cabbage, Lettuce, Peppers and Almonds. PC Code: 

014504, Petition No: PP# 4F4333 & PP#4F4324. 

M. Ruhman, 8/11/06, D323143 and 323141, Revision No. 2: Estimated Drinking Water 

Concentration of Ethylenebisdithocarbamate (EBDC) Degradate Ethylenethiourea (ETU) for the 

Use in Human Health Risk Assessment.

U.S. EPA, 9/20/05, Reregistration Eligibility Decision for Mancozeb
Mancozeb Human Health Risk Assessment DP Nos. 411742 and 411764

Page 69 of 77

Appendix A. Toxicology Profile and Executive Summaries

.

A.1.1 Toxicology Data Requirements-Mancozeb

The requirements (40 CFR 158.340) for food uses for mancozeb are in Table 1. Use of the new guideline numbers 

does not imply that the new (1998) guideline protocols were used.

Study Technical

Required Satisfied

870.1100 Acute Oral Toxicity.......................................................

870.1200 Acute Dermal Toxicity..................................................

870.1300 Acute Inhalation Toxicity..............................................

870.2400 Primary Eye Irritation ...................................................

870.2500 Primary Dermal Irritation..............................................

870.2600 Dermal Sensitization .....................................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.3100 Oral Subchronic (rodent)...............................................

870.3150 Oral Subchronic (nonrodent).........................................

870.3200 21-Day Dermal..............................................................

870.3250 90-Day Dermal..............................................................

870.3465 90-Day Inhalation..........................................................

yes

yes

yes

no

yes

yes

yes

yes

NA

yes

870.3700a Developmental Toxicity (rodent) ..................................

870.3700b Developmental Toxicity (nonrodent) ............................

870.3800 Reproduction.................................................................

yes

yes

yes

yes

yes

yes

870.4100a Chronic Toxicity (rodent)..............................................

870.4100b Chronic Toxicity (nonrodent)........................................

870.4200a Oncogenicity (rat)..........................................................

870.4200b Oncogenicity (mouse) ...................................................

yes

no

yes

yes

yes

yes

yes

yes

a

870.5100 Mutagenicity—Revers Mutation - bacterial..................

870.5300 Mutagenicity— in vivo Mammalian cell Assay ............

870.5xxx Mutagenicity— in vitro Cytogenetics

yes

yes

yes

yes

yes

yes

870.6100a Acute Delayed Neurotoxicity (hen)...............................

870.6100b 90-Day Neurotoxicity (hen) ..........................................

870.6200a Acute Neurotoxicity Screening Battery (rat).................

870.6200b 90-Day Neurotoxicity Screening Battery (rat) ..............

870.6300 Develop. Neurotoxicity .................................................

no

no

yes

yes

yes

NA

NA

yes

yes

yes

870.7485 General Metabolism......................................................

870.7600 Dermal Penetration........................................................

870.7800 Immunotoxicity .............................................................

yes

yes

yes

yes

yes

yes

Special Studies: Developmental Thyroid Study yes no

b

a This study was unacceptable but does not need to be repeated because carcinogenicity will be assessed by 

ETU (memo, Doc 013554). 

b The requirement for a developmental thyroid study is being satisfied by a study with ETU as part of an 

extended one-generation study. This study is currently underway. 
Mancozeb Human Health Risk Assessment DP Nos. 411742 and 411764

Page 70 of 77

A.2 Toxicity Profiles

Table A.2.1 Acute Toxicity Data for Mancozeb

Guideline No. Study Type MRID # Results Tox. Category

870.1100 Acute Oral 00142522 LD50 > 5000 mg/kg IV

870.1200 Acute Dermal 00142522 LD50 > 5000 mg/kg IV

870.1300 Acute Inhalation 00142522 LC50 > 5.14 mg/L IV

870.2400 Eye Irritation 00142522 corneal involvement 

clearing in < 7 days

III

870.2500 Skin Irritation 00142522 Negative IV

870.2600 Dermal Sensitization 40469501 Negative N/A

Table A.2.2 Toxicity Profile for Mancozeb 

Study Type [Guideline #], Doses MRID No. Results

Subchronic feeding - rat [870.3100]

0, 30, 60, 125, 250, or 1000 ppm

[males: 1.78, 3.49, 7.42, 14.98, 57.34 

mg/kg/day]

[females: 0, 2.20, 4.38, 9.24, 17.82, 74.64 

mg/kg/day]

00261536/

Acceptable

NOAEL=9.24 mg/kg/day in females

LOAEL=17.82 in females based on decreased serum 

thyroxine.

At HDT in males, females: ↓BW, changes in thyroid 

hormones, microscopic changes in liver and thyroids, 

increased thyroid and liver wt

Subchronic Feeding - mouse

[870.3100]

[males: 0, 1.78, 18.13, 166.9, or 1662.5 

mg/kg/day]

[females: 0, 2.34, 21.68, 233.8, or 2160.2 

mg/kg/day]

00259888 NOAEL=18.13/21.68 mg/kg/day in males/females

LOAEL=166.9/233.8 mg/kg/day in males/females, based 

on microscopic lesions of thyroid follicular cell 

hypertrophy or hyperplasia in females and decreased liver 

MFO enzyme activity in males.

Subchronic Feeding - dog

[870.3150]

[males: 0, 0.29, 2.98, 28.62, 101.53 mg/kg/day]

[females: 0, 0.32, 3.35, 28.91, 108.67 

mg/kg/day]

00261537 NOAEL=2.98/3.35 mg/kg/day in males/females.

LOAEL =28.62/28.91 mg/kg/day in males/females, based 

on dehydration, decreased body weights and food 

consumption, anemia, lymphoid depletion of the thymic 

cortex, elevated cholesterol and prostate hypogenesis.

28-Day Dermal Toxicity - rabbit [870.3200]

[0, 10, 100, or 1000 mg/kg/day]

40588201 NOAEL ≥ 1000 mg/kg/day [HDT] in males and females.

90-Day Inhalation Toxicity - rat

[870.3465]

[0, 0.018, 0.079, or 0.326 mg/L]

00159471 NOAEL=0.079 mg/L

LOAEL=0.326 mg/L based upon body weight decrements 

in males, thyroid hyperplasia in females, and decreased 

thyroxine in females.

Chronic Oral Toxicity - rat

[870.4100]

[males: 0, 0.77, 2.33, 4.83, or 30.9 mg/kg/day]

[females: 0, 1.06, 3.06, 6.72, or 40.2 

mg/kg/day]

41903601 NOAEL=4.83/6.72 mg/kg/day in males/females.

LOAEL =30.9/40.2 mg/kg/day in males/females, based on 

changes in thyroid hormone levels, microscopic thyroid 

changes, changes in thyroid weights and bilateral 

retinopathy.

Carcinogenicity - mouse

[870.4200]

0, 30, 100, or 1000 ppm

[males: 0, 4, 13, or 131 mg/kg/day]

[females: 0, 5, 18, or 180 mg/kg/day]

Much of the mancozeb degraded to ETU by 

weeks 52-80.

41981801 NOAEL for systemic toxicity=100 ppm.

LOAEL=1000 ppm based on minor body weight 

decrements and changes in thyroid hormone levels. 

Instability of test material from weeks 52-80, when much 

of the mancozeb had degraded to ethylenethiourea (ETU). 

No treatment-related increase in tumors occurred. Dosing 

considered inadequate for assessing the carcinogenic 

potential due to minimal toxicity in the study. Classified 

unacceptable.
Mancozeb Human Health Risk Assessment DP Nos. 411742 and 411764

Page 71 of 77

Table A.2.2 Toxicity Profile for Mancozeb 

Study Type [Guideline #], Doses MRID No. Results

Chronic Oral Toxicity - dog [870.4100]

[males: 0, 1.75, 7.26, 27.26, 53.52 mg/kg/day]

[females: 0, 1.84, 7.02, 29.24, or 59.72 

mg/kg/day]

41810501 NOAEL in males=1.75 mg/kg/day;

LOAEL in males=7.26 mg/kg/day, based on decreased 

body weight gain.

NOAEL in females=7.02 mg/kg/day,

LOAEL in females=29.24 mg/kg/day, based on anemia.

Acute Neurotoxicity – rat

0, 500, 1000, 2000 mg/kg/day

47126201 NOAEL=500 mg/kg/day

LOAEL=1000 mg/kg/day based on decreased motor 

activity

Subchronic Neuropathology – rat

[870.6100]

0, 20, 125, 750 ppm, or 5000 ppm

[males: 0, 1.35, 8.21, 49.7, or 339 mg/kg/day]

[females: 0, 1.67, 10.5, 63.3, or 412 

mg/kg/day]

42034101 NOAEL=8.21/10.5 mg/kg/day in males/females.

LOAEL=49.7/63.3 mg/kg/day in males/females, based on 

microscopic evidence of peripheral nerve damage and 

decreased body weight gain in females.

339/412 mg: Female mortality, ↓ BW in males (↓45%); 

Clinical signs in both sexes – reluctance to walk, etc

Developmental Neurotoxicity - rat

[870.6300]

[0, 5, 15, 30 mg/kg/day]

47872902

47872901

maternal NOAEL = 30 mg/kg/day, HDT

offspring NOAEL = 15 mg/kg/day

offspring LOAEL = 30 mg/kg/day based on decreased

pup wt (11-22%) in range-finding study

Modified DNT – rat

Tox Sci 120(2). 2011. Axelstad, et al

0, 50, 100, 150/100 mg/kg/day GD 7–PND 16

Maternal: ↓ BW gain and T4 at 50 mg/kg/day, paralysis 

and sacrifices at 150 mg/kg/day. No effects on repro 

parameters

Offspring: No effects on T4, organ wt, histopath, motor 

activity, startle response, spatial learning at any dose

Developmental Toxicity – rat

[870.3700]

0, 2, 8, 32, 128, or 512 mg/kg/day

00246663 Maternal NOAEL=32 mg/kg/day.

Maternal LOAEL=128 mg/kg/day, based on decreased 

food consumption, body weight, and body weight gains.

At 512 mg/kg/day: maternal mortality

Developmental NOAEL=128 mg/kg/day.

Developmental LOAEL=512 mg/kg/day, based on 

hydrocephaly, gross developmental defects, skeletal 

defects, cryptorchidism, abortions, increased resorptions, 

and decreased fetal weight.

Developmental Toxicity - rabbit

[870.3700]

0, 10, 30, or 80 mg/kg/day

40433001 Maternal NOAEL=30 mg/kg/day.

Maternal LOAEL=80 mg/kg/day, based on abortions, 

mortality, and clinical signs.

Developmental NOAEL=30 mg/kg/day.

Developmental LOAEL=80 mg/kg/day, based on 

abortions.

2-Generation Reproduction - rat

[870.3800]

0, 30, 120, or 1200 ppm.

[males: 0, 1.73, 6.95, 68.90 mg/kg/day]

[females: 0, 1.83, 7.47, or 79.37 mg/kg/day]

41365201 Parental NOAEL=6.95/7.47 mg/kg/day males/females

Parental LOAEL=68.90/79.37 mg/kg/day males/females, 

based on body weight decrements, increased relative 

thyroid weights, and increased incidence of thyroid 

follicular cell hyperplasia.

Reproductive NOAEL ≥ 69.90/79.37 mg/kg/day [HDT] 

males/females. No adverse reproductive or offspring 

effects were attributed to mancozeb.
Mancozeb Human Health Risk Assessment DP Nos. 411742 and 411764

Page 72 of 77

Table A.2.2 Toxicity Profile for Mancozeb 

Study Type [Guideline #], Doses MRID No. Results

Gene Mutation [870.5100, 870.5300]

- Mutagenicity: Salmonella

- in vitro mammalian: CHO/HGPRT

- mouse host-mediated

00259044

00259044

00259044

Negative with and without activation

Negative with and without activation

Negative

Cytogenetics/Structural Chromosomal 

Aberrations [870.5900, 870.5385]

- CHO cells

- in vivo bone marrow cytogenetics

- Mouse micronucleus assay

40810202

00259044

40788901

Positive (stronger response without activation)

Negative

Negative

Other Genotoxic Effects [870.5550]

- Unscheduled DNA Synthesis- hepatocytes

- Unscheduled DNA Synthesis- HeLa cells

- SCE in CHO cells

- in vitro transformation 10T1/2 cell

- in vitro transformation/promotion10T1/2 cell

- DNA damage in E. coli pol A

40611701

40810205

00259044

00259044

00259044

40810201

Negative

Pos with/without activation, not concentration dependent

Positive without activation, negative with activation

Negative

Negative

Positive (stronger response without activation)

Metabolism

[870.7485]

00262834

00262835

41656301

Rapidly absorbed after oral administration, highest 

accumulations in thyroid. No significant overall 

accumulation in the body in either rat or mouse study.

Dermal Absorption

870.7600

40955401

00250063

Dermal absorption = 1%

Immunotoxicity - rat

[870.7800]

48794801

(2012)

Acceptable/

Guideline

Negative for Immunotoxicity

Table A.2.3 Acute Toxicity of ETU

Guideline No. Study Type MRID Nos. Results Toxicity 

Category

870.1100 Acute Oral – rat N/A N/A N/A

870.1200 Acute Dermal - rabbit 458881-01 LD50 > 2000 mg/kg III

870.1300 Acute Inhalation - rat 458881-02 LC50 > 10.4 mg/L IV

870.2400 Primary Eye Irritation 458881-04 No irritation 1IV

870.2500 Primary Skin Irritation 458881-03 No irritation IV

870.2600 Dermal Sensitization N/A N/A N/A

1 The primary eye irritation study was classified unacceptable because a UV light was not observed with 

fluorescein staining, however, another study is not required (M. Lewis, 4/30/03, D289726).

Table A.2.4 Toxicity Profile of ETU

Study Type

[Guideline No.]

MRID No./

Classification

Results

Subchronic (13-week)

feeding - rat

[870.3100]

250 ppm (males: 14.28 

mg/kg/day; females: 17.81 

mg/kg/day)

000160704/1986

Acceptable/nonguideline

NOAEL = <14.28 mg/kg/day

LOAEL = 14.28 mg/kg/day, based on reduced body weight, 

changes in thyroid hormone and TSH levels, increased thyroid and 

liver weight, microscopic thyroid hyperplasia and liver 

hypertrophy.

Subchronic (13-Week) 00154192/1985 NOAEL = 1.72 mg/kg/day
Mancozeb Human Health Risk Assessment DP Nos. 411742 and 411764

Page 73 of 77

Table A.2.4 Toxicity Profile of ETU

Study Type

[Guideline No.]

MRID No./

Classification

Results

feeding - mouse

[870.3100]

0, 1, 10, 100, 1,000 ppm 

(males: 0, 0.16, 1.72, 18.18, 

168.2 mg/kg/day; females: 0, 

0.22, 2.38, 24.09, 231.1 

mg/kg/day)

Unacceptable/

Guideline

LOAEL = 18.18 mg/kg/day, based on microscopic thyroid 

hypertrophy/hyperplasia.

At the high dose, more microscopic thyroid changes and increases 

in thyroid and liver weight occurred. 

Unacceptable because ETU concentrations varied widely.

Subchronic (13-Week)

feeding - dog

[870.3100]

0, 10, 150, 2000 ppm (males: 

0, 0.39, 6.02, 66.23 

mg/kg/day; females: 0, 0.42, 

6.51, 71.62 mg/kg/day)

42174201/1991

Acceptable/

Guideline

NOAEL = 0.39 mg/kg/day

LOAEL = 6.02 mg/kg/day, based on elevated cholesterol. (Note: 

this endpoint was not considered robust enough for use in risk 

assessment)

At 6.02 mg/kg/day, thyroid effects were observed.

In high dose group: mortality, anemia, decreased activity, 

decreased thyroid hormone levels, increased thyroid weight,

microscopic thyroid hyperplasia.

Chronic

tox/carcinogenicity - SD rat

[870.4100]

0, 0.5, 2.5, 5.0, or 125 ppm

Males: 0, 0.04, 0.17, 0.37, 

8.91 mkd

Females: 0, 0.05, 0.25, 0.49, 

13.57 mkd

42607801/1992

Unacceptable/

Guideline

Concentration of ETU in feed varied widely and doses could not 

be determined. Microscopic thyroid hyperplasia occurred in the 

low-dose group. At higher doses, changes in thyroid hormone and 

TSH levels, increased thyroid weight, and grossly enlarged livers. 

Increases in thyroid follicular adenomas and pituitary adenomas in 

high-dose males. 

Chronic (24-Month)

Feeding – B6C3F1 mouse 

(NTP)

45924403/1992

Fund. Appl. Tox. 

18: 405-417

w/ and w/out 

perinatal 

exposure

This study was used to determine the Q1* for ETU of 6.01 x 10-2

(mg/kg/day)-1based upon female mouse liver adenomas and/or 

carcinomas. Thyroid follicular cell adenomas and carcinomas, 

hepatocellular adenomas and carcinomas, and pituitary adenomas 

were increased. 

Chronic (24-Month)

Feeding – Fischer 344 rat 

(NTP)

45924403/1992

Fund. Appl. Tox. 

18: 405-417

w/ and w/out 

perinatal

Thyroid follicular cell adenomas and pituitary adenomas were 

observed.

Chronic (1-year) oral

toxicity - dog

[870.4100]

0, 5, 50, or 500 ppm

(males: 0, 0.18, 1.99, 20.13 

mg/kg/day; females: 0, 0.19, 

1.79, or 20.15 mg/kg/day)

42338101/1992

Acceptable/

Guideline

NOAEL = 0.18 mg/kg/day

LOAEL = 1.99 mg/kg/day, based on increased thyroid weight and 

microscopic changes in thyroid (hypertrophy, follicular dilatation).

At the high dose, mortality, anemia, and microscopic 

hepatocellular necrosis.

4-Week Range-finding -

Dog

0, 196, 980, 4900 ppm 

(males: 0, 7.0, 34, or 172 

mg/kg/day; females: 0, 8.0, 

36, or 197 mg/kg/day)

41863401/1989

Acceptable/nonguideline

NOAEL = 7 mg/kg/day

LOAEL = 34 mg/kg/day, based on decreased levels of thyroid 

hormones, gross thyroid lesions.

Developmental toxicity

SD BR rat

[870.3700]

00093929/1980

Acceptable/nonguideline

Maternal NOAEL = <50 mg/kg/day

Maternal LOAEL = 50 mg/kg/day, based on decreased body 

weight gain (↓36%).
Mancozeb Human Health Risk Assessment DP Nos. 411742 and 411764

Page 74 of 77

Table A.2.4 Toxicity Profile of ETU

Study Type

[Guideline No.]

MRID No./

Classification

Results

50 mg/kg/day

(distilled water)

GD 6-15

Developmental NOAEL = <50 mg/kg/day

Developmental LOAEL = 50 mg/kg/day, based on numerous 

central nervous system defects (hydrocephaly and related 

malformations); gross developmental defects; skeletal defects, 

and decreased fetal weight (↓13%).

Only one dose group was included in the study.

Developmental toxicity

Wistar rat

[non-guideline]

0, 5, 10, 20, 40, 80 

mg/kg/day

45937601/1973

[Khera, K.S. 

1973. Teratology

7:243-252]

Maternal NOAEL = 40 mg/kg/day

Maternal LOAEL = 80 mg/kg/day, based on mortality (9 of 

11after 7-8 days).

Developmental NOAEL = 5 mg/kg/day

Developmental LOAEL = 10 mg/kg/day based on exencephaly, 

dilated ventricles, and hypoplastic cerebellum. At 20 mg/kg/day, 

hydrocephalus, encephalocele, meningocele, micrognathia, 

abnormal flexion of ankle, kinky or twisted tail; at ≥40 mg/kg/day: 

oligodactyl, domed head, retarded ossification of the skull 

occurred; at 80 mg/kg/day: coloboma of the eyelids, hemimelia, 

syndactyl, cleft palate, ectopic kidney, rudimentary calvarium, 

short tail, scoliosis and several types of skeletal anomalies 

occurred. Decreased fetal weight was noted at 40 mg/kg/day in 

group I (↓10%) and group III (↓21%) and at 80 mg/kg/day in 

group II (↓44%). Fetuses at 40 mg/kg/day in group II had weights 

comparable to controls. Number of live fetuses and corpora lutea 

were comparable to controls in all groups. 

Developmental toxicity

SD rat

(1) 0, 5, 10, 20, 30, 40, or 80 

mg/kg/day from GD 7-21.

(2) 0, 20, 25, or 30 

mg/kg/day from GD 7 to 

PND 15

45924404/1979

[Chernoff, et al., 

J. Toxicol. Env. 

Health 5: 821-

834]

Maternal NOAEL = 40 mg/kg/day (or lower).

Maternal LOAEL = 80 mg/kg/day, based on reduced body weight 

and 25% maternal mortality.

Gestational exposure only:

Developmental NOAEL = 10 mg/kg/day (↓7% fetal BW)

Developmental LOAEL = 20 mg/kg/day, based on hydrocephalus 

(12 fetuses/5 litters).

Decreased ossification was also observed at 30 mg/kg/day and 

above; at 40 mg/kg/day, encephalocele, kyphosis, and digit defects 

(oligodactyl, syndactyl) were also observed. At 80 mg/kg/day, 

fetal mortality was increased and there were increases in cleft 

palate, limb defects (micromelia, hemimelia), edema, and 

micrognathia. 

Gestational and postnatal exposure:

Postnatal toxicity at

30 mg/kg/day included hydrocephalus, dome-shaped heads, and 

pup mortality. 

Developmental toxicity

Wistar rat

[non-guideline]

0, 15, 30, 45 mg/kg

Dams received a single oral 

dose on gestation day 15.

MRID 48985801

[Khera and 

Tryphonas 

Tox Appl Pharm 

42:85-97. 1977]. 

Maternal NOAEL/LOAEL not reported

Developmental NOAEL = 15 mg/kg

Developmental LOAEL = 30 mg/kg based on postnatal mortality, 

hydrocephaly, microphthalmia, cerebellar dysplasia, cerebral 

atrophy, and in survivors, motor defects and dome-shaped head.

Developmental toxicity 

Wistar rat

0 or 240 mg/kg

No MRID 

[Ruddick and 

Khera. 

No maternal toxicity observed.

Teratogenic effects in fetuses from GD 10-21; greatest frequency 

of defects between GD 12-15; no defects before GD 10; ETU 
Mancozeb Human Health Risk Assessment DP Nos. 411742 and 411764

Page 75 of 77

Table A.2.4 Toxicity Profile of ETU

Study Type

[Guideline No.]

MRID No./

Classification

Results

Dams received a single dose 

on one gestation day between 

GD 6-21

Teratology 

12:277-282, 

1975]

affected development of brain, kidney, eye, and axial and 

appendicular systems

Developmental toxicity 

SD rat

0, 15, 25, or 35 mg/kg/day 

from GD 6-20

No MRID 

[Saillenfait, et 

al., Fund. Appl. 

Toxicol. 17: 300-

408, 1991]

Maternal NOAEL

Maternal LOAEL = 15 mg/kg/day, based on decreased body 

weight gain

Developmental NOAEL = 15 mg/kg/day

Developmental LOAEL = 25 mg/kg/day, based on dilated 

ventricles of the brain, hydroureter, short/kinky tail, and dilated 

ureters. At 35 mg/kg/day, hydrocephaly, anencephaly, 

meningocele, meningorrhea, hyrdronephrosis, dilated renal pelvis, 

and vertebral abnormalities were observed.

Developmental toxicity 

Wistar-Imamichi rats

0, 10, 20, 30, 40, 50 

mg/kg/day 

GD 6-15.

45924405/1978

[Teramoto, et al., 

Congenital 

Anomalies 18: 

11-17, 1978]

Developmental NOAEL <10 mg/kg/day

Developmental LOAEL = 10 mg/kg/day, based on dilated brain 

ventricles. At higher doses, fetal death, meningocele, 

micrognathia, hydronephrosis, renal agenesis, uterine hypoplasia, 

skeletal anomalies, short/kinky tail, and scoliosis were observed. 

Developmental 

New Zealand White Rabbit

[870.3700]

0.5% aqueous 

methylcellulose

0, 5, 15, 50 mg/kg/day

GD 7-29

47976403/2010

Acceptable/

Guideline

Maternal NOAEL = 5 mg/kg/day

Maternal LOAEL = 15 mg/kg/day based on increased 

postimplantation loss

Developmental NOAEL = 5 mg/kg/day 

Developmental LOAEL = 15 mg/kg/day based on increased 

postimplantation loss

At 50 mg/kg/day, postimplanation loss, decreased fetal BW 

(↓10%), hydrocephaly (1), and domed head (2) were observed.

Developmental toxicity 

Syrian Golden hamsters

0, 90, 270, 810 mg/kg/day 

from GD 6-13.

45924405/1978

[Teramoto, et al., 

Congenital 

Anomalies 18: 

11-17, 1978]

Developmental NOAEL = 90 mg/kg/day

Developmental LOAEL = 270 mg/kg/day, based on skeletal 

malformations and short/kinky tail. At 810 mg/kg/day, fetal 

deaths, dilated brain ventricles, cleft palate, micrognathis, and anal 

atresia were observed.

Developmental toxicity 

JCL-ICR mouse

0, 200, 400, or 800 

mg/kg/day.

GD 7-15

45924405/1978

[Teramoto, et al., 

Congenital 

Anomalies 18: 

11-17, 1978]

No maternal or developmental toxicity was observed.

2-Generation

reproduction – SpragueDawley rat

[870.3800]

0, 2.5, 25, 125 ppm

42391701/1992

Unacceptable/

Non-guideline

42391801/1992

ETU content data

Doses on mg/kg/day basis could not be determined.

Parental: microscopic thyroid hyperplasia/hypertrophy in mid 

and/or high-dose groups.

No reproductive effects attributed to treatment.

Unacceptable because of stability problems (mkd could not be 

calculated) with test material and poor record keeping.

Dermal absorption – SD 

COBS CD rat

[870.7600]

40312601/1987

Acceptable

Dermal absorption = 26%

Immunotoxicity - rat

[870.7800]

48794502/2012

Acceptable/

Guideline

Negative for Immunotoxicity
Mancozeb Human Health Risk Assessment DP Nos. 411742 and 411764

Page 76 of 77

Appendix B. Physical/Chemical Properties

Table B.1 Physicochemical Properties of Mancozeb.

Parameter Value Reference

Melting point/range Decomposes at 150 oC RCB No. 4368, 11/9/88, G. 

Makhijani pH 6.5 (25% slurry in water)

Density 0.41 g/cc (packed)

Water solubility 1.1 μg/mL at room temperature

Solvent solubility Insoluble in most organic solvents DEB No. 4689, 12/16/88, 

G. Makhijani 

Vapor pressure Not applicable; negligible RCB No. 4368, 11/9/88, G. 

Makhijani

Dissociation constant, pKa Not applicable; does not dissociate DEB No. 4750, 1/24/89, G. 

Makhijani 

Octanol/water partition coefficient, 

Log(KOW)

3.24 at room temperature RCB No. 4368, 11/9/88, G. 

Makhijani 

UV/visible absorption spectrum Not available

Physicochemical properties not available for metabolite ETU
Mancozeb Human Health Risk Assessment DP Nos. 411742 and 411764

Page 77 of 77

Appendix C. 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 

the Pesticide Handlers Exposure Database Version 1.1 (PHED 1.1); the Agricultural Handler 

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

(ORETF) database; the Agricultural Re-entry Task Force (ARTF) database; and other registrantsubmitted studies; (1) are subject to ethics review pursuant to 40 CFR 26, (2) have received that 

review, and (3) 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 the Agency website.5

 

5

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

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