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 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460 

 OFFICE OF 

PREVENTION, PESTICIDES 

AND TOXIC SUBSTANCES 

Date: 6/11/07 

 

MEMORANDUM

SUBJECT: 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. 

 DP Barcode: D327307 & D327318. Risk Assessment Type: Single 

 Chemical Aggregate. 

FROM: Donna Davis, Risk Assessor 

 Reregistration Branch 1 

 Health Effects Division (7509P) 

 AND 

 Timothy C. Dole, CIH, Industrial Hygienist 

 Kit Farwell, D.V.M. 

 Christine L. Olinger, Chemist 

 Reregistration Branch 1 

 Health Effects Division (7509P) 

THROUGH: Whang Phang, Branch Senior Scientist 

 Michael S. Metzger, Chief 

 Reregistration Branch 1 

 Health Effects Division (7509P) 

TO: Cynthia Giles-Parker, Branch Chief 

 Mary Waller, Risk Manager 

 Lisa Jones, Risk Manager 

 Fungicide-Herbicide Branch 

 Registration Division (7505P) 

Attached please find the human health risk assessment for the active ingredient, 

mancozeb, to support requested new uses on broccoli, cabbage, lettuce, peppers and 

almonds. This document addresses risks from exposure to mancozeb and mancozebderived ethylenethiourea (ETU) only. A separate assessment addressing risk from ETU 

derived from all ethylene bisdithiocarbamate (EBDC) pesticides is forthcoming. 
Mancozeb Human Health Risk Assessment D327307 & D327318

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Table of Contents 

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

2.0 Ingredient Profile.................................................................................................. 8 

2.1 Summary of Registered/Proposed Uses.......................................................... 8 

2.2 Structure and Nomenclature ........................................................................... 9 

2.3 Physical and Chemical Properties................................................................ 10

3.0 Hazard Characterization.................................................................................... 11 

3.1 Toxicology Profile ........................................................................................... 11 

3.2 Mancozeb: Recommendation for a Developmental Neurotoxicity Study 

 and Rationale for UFDB ................................................................................ 16 

3.3 Summary of Toxicological Doses and Endpoints for Mancozeb and ETU 

 for Use in Human Risk Assessments........................................................... 17 

3.4 Endocrine Disruption ..................................................................................... 20

4.0 Public Health Data.............................................................................................. 20

5.0 Dietary Exposure/Risk Characterization ......................................................... 21 

5.1 Pesticide Metabolism and Environmental Degradation.............................. 21 

5.2 Dietary Exposure and Risk ............................................................................ 30

6.0 Residential (Non-Occupational) Exposure/Risk Characterization ................ 35

6.1 Residential Handler Exposures and Risks.................................................... 36 

6.2 Residential Postapplication Exposure........................................................... 38 

6.3 Spray Drift....................................................................................................... 43

7.0 Aggregate Risk Assessments and Risk Characterization................................ 44 

7.1 Acute Aggregate Risk ..................................................................................... 46 

7.2 Short/Intermediate-Term Aggregate Risk ................................................... 46 

7.3 Long-Term (Chronic) Aggregate Risk.......................................................... 51 

7.4 Cancer Aggregate Risk................................................................................... 51 

7.5 ETU Aggregate Exposure from All Sources................................................. 52

8.0 Cumulative Risk Characterization/Assessment............................................... 52

9.0 Occupational Exposure/Risk Pathway.............................................................. 53 

9.1 Occupational Handler Exposures and Risks............................................... 53 

9.2 Occupational Postapplication Exposures and Risks.................................... 56
Mancozeb Human Health Risk Assessment D327307 & D327318

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10.0 Data Needs and Label Recommendations ........................................................ 59 

10.1 Toxicology........................................................................................................ 59 

10.2 Residue Chemistry.......................................................................................... 59 

10.3 Occupational and Residential Exposure....................................................... 60

11.0 Environmental Justice.................................................................................... 60

12.0 Regulatory Recommendations........................................................................... 60

References:....................................................................................................................... 61 
Mancozeb Human Health Risk Assessment D327307 & D327318

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1.0 Executive Summary

Background 

Dow AgroSciences LLC has proposed to amend the use pattern for the 80% wettable 

powder (WP) formulation of mancozeb (Dithane® M45 Fungicide; EPA Reg. No. 

62719-387) to include uses on broccoli, cabbage, lettuce, peppers and almonds. In 

conjunction with the proposed new uses, Dow AgroSciences has proposed, in petitions 

PP#4F4333 (broccoli, cabbage, lettuce and peppers) and PP#4F4324 (almonds), the 

establishment of permanent tolerances for residues of mancozeb in/on the following raw 

agricultural commodities: 

Broccoli.......................................................................13 ppm 

 Cabbage.......................................................................10 ppm 

 Lettuce........................................................................10 ppm 

 Peppers........................................................................7 ppm 

 Almond nuts........................................................................................0.1 ppm 

 Almond hulls.................................................................10 ppm 

Mancozeb Toxicology Considerations 

Mancozeb is not acutely toxic via the oral, dermal or inhalation routes of exposure. 

Further, mancozeb is not a skin irritant nor is it a skin sensitizer, although it does cause 

mild eye irritation. The findings in multiple studies demonstrate that the thyroid is a 

target organ for mancozeb. Thyroid toxicity was manifested as alternations in thyroid 

hormones, increased thyroid weight, 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 sings (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. 

There is a data gap for a developmental neurotoxicity study with mancozeb. An 

additional uncertainty factor of 10X is applied to account for this data gap. An acute 

neurotoxicity study has recently been received and is under review. Preliminary review 

indicates no concerns for neurotoxicity at the high dose of 2000 mg/kg. 

Based on the lack of evidence of pre- and/or postnatal susceptibility resulting from 

exposure to mancozeb, and considering the lack of residual uncertainties, no additional 

FQPA Safety Factor beyond the 10X applied to account for the missing studies is 

required. 

Mancozeb doses and endpoints are summarized below. 

Exposure Route, Duration Mancozeb Dose in mg/kg/day (study/effects)

Acute dietary (females 13-49) NOAEL of 128 (Developmental rat/hydrocephaly, malformations) 

Acute dietary (gen. US pop.) No applicable endpoint/dose identified 

Chronic dietary (gen. US pop.) NOAEL of 4.83 (Rat chronic/thyroid effects) 

Incidental oral, any duration NOAEL of 9.24 (Subchronic oral rat/decreased thyroxine) 
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Dermal, short-, intermediate-term Quantitation not required (no toxicity at limit dose in dermal tox study) 

Dermal, long term NOAEL of 4.83 (Rat oral chronic/carcinogenicity/thyroid effects) 

Inhalation, any duration NOAEL of 21 (Subchronic inhalation rat/thyroid hyperplasia and 

decreased thyroxine in females) 

Combined Uncertainty factors (UFs) for mancozeb dietary assessments are 1000X. The level of concern 

(LOC) for the residential and aggregate assessments is 1000. The LOC for the occupational risk 

assessment is 100. Mancozeb dermal absorption is 1%. Inhalation absorption is 100%. 

ETU Toxicology Considerations 

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

risks from exposure to mancozeb-derived ETU, a degradate of mancozeb. 

 

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 

Due to the limited nature of the toxicological database for ETU based on guideline 

studies as well as the need for a developmental neurotoxicity study, and a comparative 

thyroid assay, HED applied a database uncertainly factor of 10X to the dietary, 

residential and aggregate risk assessments for ETU. No additional FQPA safety factor 

beyond the 10X database uncertainty factor is required since teratogenic effects seen in 

the database are well characterized, the dose-response relationship is well characterized 

and the doses selected for risk assessment address concerns for developmental toxicity. 

ETU endpoints used for risk assessment are summarized below. 

Exposure Route, Duration ETU Dose in mg/kg/day (study/effects)

Acute dietary (females 13-49) NOAEL of 5 (Developmental rat/developmental brain defects) 

Acute dietary (gen. US pop) No applicable endpoint/dose identified 

Chronic dietary (gen. US pop.) NOAEL of 0.18 (Chronic dog/thyroid toxicity) 

Incidental oral, any duration NOAEL of 7 (4-week Dog/thyroid toxicity) 

Oral, short/intermediate-term NOAEL of 5 (Developmental rat/developmental brain defects) 

Dermal, short/intermediate-term 

 Toddlers NOAEL of 7 (4-week Dog/thyroid toxicity) 

Dermal, short/intermediate- term 

 Females 13-49 yrs NOAEL of 5 (Developmental rat/developmental brain defects) 

Dermal, Long-Term NOAEL of 0.18 (Chronic dog/thyroid toxicity) 

Inhalation, Short/Int-Term NOAEL of 5 (Developmental rat/developmental brain defects) 

Inhalation, Long-Term NOAEL of 0.18 (Chronic dog/thyroid toxicity) 

Combined UFs for dietary assessments are 1000X. The level of concern (LOC) for ETU residential and 

aggregate assessments is 1000. The LOC for occupational assessments is 100. Dermal absorption for ETU 

is 26%, while inhalation absorption is 100%. Dermal and inhalation exposures can be combined, since the 

toxic effects from these two routes of exposure are similar for similar durations.
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Residue Chemistry Considerations 

Provided the requested label revisions are made to restrict the use of “U-boom” type 

devices and to omit the requirement for a surfactant as part of the almond use pattern, 

there are no residue chemistry deficiencies that would preclude the establishment of the 

requested tolerances or granting of the requested registrations. Analytical methods are 

available for the enforcement of tolerances for the plant commodities which are the 

subject of this request. Adequate crop field trial data have been submitted to support the 

requested new uses of the WP formulation of mancozeb on broccoli, cabbage, lettuce, 

peppers and almonds. HED notes that the data submitted would not only support the use 

of the WP formulation as requested in this petition, but would also support the use of a 

dry flowable formulation on the same crops with the same use patterns and restrictions. 

International Harmonization 

HED has recommended that all tolerances for the EBDC pesticides be expressed in terms 

of CS2, therefore, harmonizing the tolerance definition with the Codex tolerance 

expression. However, the actual tolerance levels for cabbage, head lettuce, leaf lettuce 

peppers and almond hulls cannot be harmonized with current Codex values either 

because U.S. field trial data values exceeded the Codex MRL or because the Codex MRL 

was significantly higher than that recommended in the U.S. 

Drinking Water Considerations 

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. 

Dietary Risk Assessments 

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 risks of concern were identified for either mancozeb or 

mancozeb-derived ETU. 

The chronic dietary exposure and risk assessments (noncancer 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, 

as well as processing and cooking factors. No chronic noncancer risks of concern were 

identified for mancozeb or mancozeb-derived ETU. Further, the estimated cancer risk for 

food alone and aggregated food and water are not of concern. 

Residential Exposure and Risk 

No new residential uses are being added to the label as a result of the actions that are the 

subject of these two petitions. However, in light of the reconsideration of the toxicity 

data requirements for mancozeb, the residential exposures and risks for mancozeb and 

mancozeb-derived ETU were revisited. All residential exposure scenarios had MOEs 
Mancozeb Human Health Risk Assessment D327307 & D327318

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that were above the level of concern of 1000, with the exception of incidental oral risks 

for toddlers exposed to transplanted turf with a PHI of 3 days. Based on the current 

LOC, a PHI of 5 days would be required to assure that incidental oral risks to toddlers 

exceeded the LOC of 1000. 

Aggregate Risk Assessments 

HED conducted acute, short and intermediate term and chronic non cancer aggregate 

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

assessment for mancozeb-derived ETU. Assuming a 5-day PHI for the existing use on 

sod farm turf, there are no aggregate risks of concern for mancozeb or mancozeb-derived 

ETU. 

Occupational Exposure and Risk 

HED conducted occupational exposure and risk assessments for the proposed new uses. 

Provided the WP label includes a requirement for a PF5 respirator, there are no risks of 

concern. HED notes that the occupational risks are significantly lower with the dry 

flowable (DF) formulation and that a respirator would not be required for the DF 

formulation. 

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. 

Review of Human Research

This risk assessment does not rely on any data from studies in which human subjects 

were intentionally exposed to a pesticide or other chemical. 

Data Gaps 

The following residue chemistry data needs have been identified and should be resolved 

with these new uses. 

• The label should be amended to prohibit the use of a “U-boom” application device. 

• The proposed use for almonds must be amended to remove the instruction to add a surfactant to 

the spray mixture 

• The petitioner should provide amended Section Fs to express the tolerances as carbon disulfide, 

and change the proposed levels to broccoli, 7 ppm; cabbage, 9 ppm; head lettuce, 3.5 ppm; leaf 

lettuce, 18 ppm; pepper, 12 ppm: almond hulls, 4 ppm. 

Additional data gaps for mancozeb and ETU were identified in the RED are summarized 

in Section 10.0. Those data remain outstanding. 

Regulatory Recommendations 

Provided the existing label for the sod farm turf use of mancozeb is revised to stipulate an 

5-day PHI, there is nothing in this mancozeb specific risk assessment to preclude the 

establishment of the requested tolerances at the levels stipulated below. 

Further, HED notes that the new uses that are the subject of this action have been 
Mancozeb Human Health Risk Assessment D327307 & D327318

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included in the forthcoming ETU aggregate risk assessment. The ETU aggregate 

assessment considers exposure and risk from ETU derived from all existing and pending 

uses of the EBDC pesticides. The addition of these new mancozeb uses does not result in 

aggregate ETU exposures or risks of concern when considered with the existing and 

pending uses of EBDC pesticides. 

Provided the requested label and Section F revisions are made as noted above under data 

gaps, HED recommends the following tolerance levels based on the available data: 

Broccoli................................................................................................................... 7.0 ppm 

 Cabbage................................................................................................................... 9.0 ppm 

 Lettuce, head ........................................................................................................... 3.5 ppm 

 Lettuce, leaf.............................................................................................................. 18 ppm 

 Pepper ...................................................................................................................... 12 ppm 

 Almond.................................................................................................................... 0.1 ppm 

 Almond, hulls.......................................................................................................... 4.0 ppm

 

2.0 Ingredient Profile

Mancozeb is a member of the EBDC group of fungicides and is currently registered for 

use on a variety of fruit, vegetable, nut, and field crops. 

2.1 Summary of Registered/Proposed Uses 

The petitioner is proposing to add uses on broccoli, cabbage, lettuce, pepper and almonds 

to the product label for the 80% WP (EPA Reg. No. 62719-387) formulation only. The 

proposed use directions for broccoli, cabbage, lettuce, pepper and almonds are 

summarized in Table 2.1, below. 

Table 2.1 Summary of Directions for New Uses of Mancozeb 

Applic. 

Timing, Type, 

and Equip. 

Formulation 

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 

Broccoli and Cabbage (PP#4F4333) 

Postemergence 

Broadcast 80% WP 1.6 6 (implied) 9.6 7 

Applications are to be 

made as soon as disease 

is present. A minimum 

retreatment interval 

(RTI) of 7 days is 

specified. 

Lettuce (PP#4F4333) 

Postemergence 

Broadcast 80% WP 1.6 6 (implied) 9.6 10 

Applications are to begin 

when disease appears. 

Use limited to all states 

except CA. A minimum 

RTI of 7 days is 

specified. 
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Table 2.1 Summary of Directions for New Uses of Mancozeb 

Applic. 

Timing, Type, 

and Equip. 

Formulation 

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 

1.6 4 (implied) 6.4 14 

Applications are to begin 

when disease appears. 

Use limited to CA. A 

minimum RTI of 7 days 

is specified. 

Pepper (PP#4F4333) 

1.6 6 (implied) 9.6 7 

Applications are to begin 

when disease appears. 

Use limited to west of 

the Mississippi River. A 

minimum RTI of 7 days 

Postemergence is specified. 

Broadcast 80% WP 

2.4 6 (implied) 14.4 7 

Applications are to begin 

when disease appears. 

Use limited to east of the 

Mississippi River. A 

minimum RTI of 7 days 

is specified. 

Almonds (PP#4F4324) 

Postemergence 

Broadcast 

Ground or 

aerial 

80% WP 4.8 3 (implied) 14.4 

Last 

applic. to 

be made 

no later 

than 5 

weeks 

after petal 

fall 

Applications are to begin 

at the dormant to 

popcorn growth stages 

and continue with a 

minimum 7-day 

retreatment interval. 

Aerial applications are to 

be made in a minimum 

of 10 gal/A. The grazing 

of livestock in treated 

areas is prohibited. 

2.2 Structure and Nomenclature 

The chemical structures and nomenclature for mancozeb and its major metabolite, 

ethylenethiourea (ETU) are presented in Table 2.2, below. 

Table 2.2 Mancozeb and ETU Structures and Nomenclature

Chemical structure 

N

H

S

S

N

H

S

Mn

S

Zn

x

y

Common name Mancozeb 
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Table 2.2 Mancozeb and ETU Structures and Nomenclature

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) 80% WP (Dithane® M45 Fungicide; EPA Reg. No. 62719-387) 

Chemical structure of ETU 

metabolite 

HN NH

S

Ethylenethiourea 

2.3 Physical and Chemical Properties 

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. Other 

identifying codes and characteristics include: 

Empirical Formula: (C4H6MnN2S4)x (Zn)y

Molecular Weight: (265.3)x + (65.4)y

CAS Registry No.: 8018-01-7 

PC Code: 014504 

The physicochemical properties of mancozeb are summarized in table 2.3, below. 

 

Table 2.3 Physicochemical Properties of Mancozeb. 

Parameter Value Reference 

Melting point/range Decomposes at 150 oC 

pH 6.5 (25% slurry in water) 

Density 0.41 g/cc (packed) 

Water solubility 1.1 μg/mL at room temperature 

RCB No. 4368, 11/9/88, G. 

Makhijani 

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 
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3.0 Hazard Characterization 

3.1 Toxicology Profile 

D317371, 6/3/2005, K. Farwell 

D317369, 6/3/2005, K. Farwell 

The hazard characterization for mancozeb and its major metabolite, ETU is discussed in 

detail in the document entitled Mancozeb. Health Effects Division (HED) Human Health 

Risk Assessment to Support Reregistration (D317371, K. Farwell, 6/3/2005). Revised 

mancozeb endpoints and data gaps are described in a separate memo entitled Mancozeb 

Toxicity Endpoints for Risk Assessment (D317369, K. Farwell, 6/3/2005). The ETU data 

requirements and uncertainty factors outlined in the 6/3/2005 risk assessment remain 

unchanged. However, the data requirements and uncertainty factors for the mancozeb 

risk assessment document have been revised as noted in Section 3.1 below. The hazard 

characterizations for both mancozeb and ETU are briefly summarized below. 

Mancozeb 

Mancozeb is not acutely toxic via the oral, dermal or inhalation routes of exposure. 

Further, mancozeb is not a skin irritant nor is it a skin sensitizer, although it does cause 

mild eye irritation. The findings in multiple studies demonstrate that the thyroid is a 

target organ for mancozeb. Thyroid toxicity was manifested as alternations in thyroid 

hormones, increased thyroid weight, and microscopic thyroid lesions (mainly thyroid 

follicular cell hyperplasia). These effects are due to the ETU metabolite. In a subchronic 

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

with associated clinical sings (abnormal gait and limited use of rear legs) and loss of 

muscle mass. An acute neurotoxicity study has recently been received and is under 

review. Preliminary review indicates no concerns for neurotoxicity at the high dose of 

2000 mg/kg. Other toxicity 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 rapidly absorbed and eliminated in the urine. In oral rat metabolism studies 

with radiolabelled mancozeb and other EBDCs, an average 7.5% in vivo metabolic 

conversion of EBDC to ETU occurred, on a weight-to-weight basis. Metabolism data 

indicate mancozeb does not bio-accumulate. Mancozeb has been tested in a series of in 

vitro and in vivo genotoxicity assays, which have shown that it exhibits weak genotoxic 

potential. 

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. Historically, mancozeb’s potential for carcinogenicity has been 

based on its 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 the 
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ETU cancer potency factor has been used in past and current risk assessments for 

assessing cancer risk associated with mancozeb uses. 

There is a data gap for a developmental neurotoxicity study with mancozeb. An 

additional uncertainty factor of 10X is applied to account for this data gap. 

Developmental defects in the rat developmental toxicity study included hydrocephaly, 

skeletal system defects, and other gross defects which occurred at a dose causing 

maternal mortality and did not indicate increased susceptibility of offspring. Abortions 

occurred in the rabbit developmental toxicity study at the high dose which also caused 

maternal mortality, and there was no indication of enhanced susceptibility of offspring in 

the rabbit. There was no evidence of reproductive toxicity in the 2-generation 

reproduction study in rats. Based on the lack of evidence of pre- and/or postnatal 

susceptibility resulting from exposure to mancozeb, and considering the lack of residual 

uncertainties, no additional FQPA Safety Factor beyond the 10X applied to account for 

the missing studies is required. 

ETU

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

literature to assess hazard for ETU. ETU is not acutely toxic via the dermal or inhalation 

routes of exposure. There is no data on acute oral toxicity. ETU is not a skin or eye 

irritant. 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 study were similar to those 

seen with mancozeb, and included hydrocephaly and related lesions, skeletal system 

defects, and other gross defects 

Due to the limited nature of the toxicological database for ETU based on guideline 

studies as well as the need for a developmental neurotoxicity study, and a comparative 

thyroid assay, HED applied a database uncertainly factor of 10X to the dietary, 

residential and aggregate risk assessments for ETU. No additional FQPA safety factor 

beyond the 10X database uncertainty factor is required since teratogenic effects seen in 

the database are well characterized, the dose-response relationship is well characterized 

and the doses selected for risk assessment address concerns for developmental toxicity. 

The results of acute toxicity testing for mancozeb are shown in Table 3.1.1, below. A 

toxicity profile for mancozeb technical is shown in Table 3.1.2, below. 
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Table 3.1.1 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 

870.6100 acute delayed neurotox (hen) none 

870.6200 acute neurotoxicity Study recently submitted & 

under review 

Table 3.1.2. Toxicity Profile for Mancozeb Technical

Study Type [Guideline #] 

Doses 

MRID No. Results 

Subchronic feeding - rat [870.3100] 

[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=9.24/14.98 mg/kg/day in females/males 

LOAEL=17.82 in females/males based on decreased 

serum thyroxine. 

In males, body weight decrements, changes in thyroid 

hormones and liver enzymes, microscopic changes in liver 

and thyroids, increased absolute and relative thyroid 

weights, and increased relative liver weights were 

observed at the LOAEL of 57.34 mg/kg/day. 

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.
Mancozeb Human Health Risk Assessment D327307 & D327318

Page 14 of 62 

Table 3.1.2. Toxicity Profile for Mancozeb Technical

Study Type [Guideline #] 

Doses 

MRID No. Results 

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. 

Subchronic Neuropathology - rat 

[870.6100] 

[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. 

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. 

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. 

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. 

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. 

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. 
Mancozeb Human Health Risk Assessment D327307 & D327318

Page 15 of 62 

Table 3.1.2. Toxicity Profile for Mancozeb Technical

Study Type [Guideline #] 

Doses 

MRID No. Results 

2-Generation Reproduction - rat 

[870.3800] 

[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. 

Chronic Toxicity/Carcinogenicity - rat 

[870.4100] 

41903601 See chronic toxicity in rats, above. 

Developmental Neurotoxicity - rat 

[870.6300] 

none N/A 

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 Penetration 

870.7600 

40955401 

00250063 

Dermal absorption = 1% 

Domestic Animal Safety 

870.7200 

None 
Mancozeb Human Health Risk Assessment D327307 & D327318

Page 16 of 62 

3.2 Mancozeb: Recommendation for a Developmental Neurotoxicity Study and 

 Rationale for UFDB 

As part of the reevaluation of mancozeb to support the new uses that are the subject of 

this action, the uncertainty factors and need for a DNT study were reviewed for 

compliance with current policy. The proposed 158 Guidelines state that a DNT study 

should be required using a weight-of-the-evidence approach when a pesticide causes 

neuropathology in adult animals. 

Mancozeb had been evaluated by the Hazard Identification Assessment Review 

Committee (HIARC) in 1999, 2001, and 2003. At the last meeting of the committee in 

2003, the HIARC removed the requirement for a DNT study with mancozeb which had 

been levied in previous HIARC meetings. In 2003, the HIARC removed the DNT 

requirement because the hydrocephaly occurring in the mancozeb developmental study 

was attributed to ETU, a mancozeb metabolite. Peripheral nerve injury which occurred 

in the subchronic neuropathology study with mancozeb was not considered sufficient 

indication for a developmental neurotoxicity with mancozeb at that time. 

The EBDC team reconsidered the peripheral nerve injury observed in the subchronic 

neurotoxicity study with mancozeb as part of its reevaluation. The peripheral nerve 

injury is characterized as a myelinopathy and included demyelination, myelin 

phagocytosis, Schwann cell proliferation, thickened myelin sheath, intrasheath ellipsoids, 

neurofibrillary degeneration, and myelin ovoids, bubbles, and debris at the study LOAEL 

of 50 mg/kg/day. The NOAEL for the subchronic neurotoxicity study was 8 mg/kg/day. 

An acute neurotoxicity study has recently been received and is under review. Preliminary 

review indicates that there are no neuropathology or FOB changes in this study; reduced 

motor activity on day one may be due to systemic toxicity and not due to neurotoxicity. 

The EBDC team considered whether the DNT study required for ETU would adequately 

address any concerns for developmental neurotoxicity triggered by the peripheral nerve 

injury seen in the subchronic neurotoxicity study. While ETU is the major mancozeb 

metabolite, accounting for 40% of the radioactivity in urine, there are no reports of nerve 

injury from ETU. HED notes that the toxicity database for ETU is limited. 

The EBDC team considered the possibility that the myelinopathy seen in the mancozeb 

subchronic neurotoxicity study might be due to CS2. CS2 is known to cause cause 

peripheral nerve injury. Given that a DNT for ETU was required, the team considered the 

possibility that a DNT conducted with ETU would address the potential hazard for 

peripheral nerve injury; that is, if the metabolic profile demonstrated that significant 

amounts of CS2 could be expected as degradation products of ETU, then the potential for 

developmental neurotoxicity would be addressed with the ETU DNT and no further study 

would be required. However, after considering the structure of ETU, as well as the 

metabolic profile for mancozeb, the team determined that generation of CS2 from ETU 

was unlikely to be significant, but that greater amounts of CS2 would likely be generated 

from breakdown of the parent mancozeb molecule or other metabolites. Therefore, if 
Mancozeb Human Health Risk Assessment D327307 & D327318

Page 17 of 62 

CS2 was expected to be the cause of any developmental neurotoxicity, that toxicity would 

not be measured in a study which dosed only with ETU. 

After evaluating all the evidence, the EBDC Team concluded that a DNT study should be 

required for mancozeb and a 10X database uncertainty factor to account for lack of this 

study should be applied in addition to a 100X for inter- and intra-species extrapolation 

when conducting the dietary, residential and aggregate risk assessments. 

3.3 Summary of Toxicological Doses and Endpoints for Mancozeb and ETU for 

 Use in Human Risk Assessments 

Doses and endpoints for mancozeb and ETU are summarized in the Tables 3.3.1 and 

3.3.2, respectively. As noted above, a detailed description of the toxicity database, as 

well as details on the selection of endpoints and doses for risk assessment for both 

mancozeb and its degradate, ETU, are contained in the 6/3/2005 risk assessment. The 

only deviation from that assessment is the addition of a 10X UFDB for mancozeb which is 

detailed in Section 3.2 of this document. 

Table 3.3.1 Summary of Toxicological Doses and Endpoints for Mancozeb 

Exposure/Scenario 

Point of 

Departure 

Uncertainty/F

QPA SF 

RfD, PAD, 

Level of 

Concern for 

RA Study & Toxic Effects 

Mancozeb Dietary Exposures 

Acute Dietary 

(Females 13 – 49) 

NOAEL = 128 

mg/kg/day 

UFA = 10 

UFH = 10 

UFDB=10 

Acute RfD = 

0.13 mg/kg/day 

Acute PAD = 

0.13 mg/kg/day 

Developmental Toxicity 

in the rat 

LOAEL = 512 mg/kg/day 

based on hydrocephaly 

and other malformations 

Acute Dietary 

(general population) No appropriate endpoint was identified from oral toxicity studies. 

Chronic Dietary 

(all populations) 

NOAEL = 

4.83 mg/kg/day 

UFA = 10 

UFH = 10 

UFDB=10 

Chronic RfD = 

0.005 

mg/kg/day 

Chronic PAD = 

0.005 

mg/kg/day 

Toxicity/Carcinogenicity 

in the rat 

LOAEL = 30.9 mg/kg/day 

based on changes in 

thyroid toxicity (changes 

in thyroid hormone levels, 

microscopic thyroid 

changes and changes in 

thyroid weights) 

Mancozeb Oral Exposures 

Incidental Oral 

(Short- or 

Intermediate-Term) 

NOAEL = 9.24 

mg/kg/day 

UFA = 10 

UFH = 10 

UFDB=10 

Residential 

LOC = 1000 

Subchronic Toxicity 

Study in the rat 

LOAEL = 17.82 

mg/kg/day based on 

decreased thyroxine 

Mancozeb Dermal Exposures 

Dermal (Short-, and 

Intermediate-Term) 

Risk Assessment not required. No systemic toxicity via the dermal route at 1000 

mg/kg/day and no developmental concerns. 
Mancozeb Human Health Risk Assessment D327307 & D327318

Page 18 of 62 

Table 3.3.1 Summary of Toxicological Doses and Endpoints for Mancozeb 

Exposure/Scenario 

Point of 

Departure 

Uncertainty/F

QPA SF 

RfD, PAD, 

Level of 

Concern for 

RA Study & Toxic Effects 

Dermal 

(Long-Term) 

NOAEL = 4.83 

mg/kg/day 

DA = 1% 

UFA = 10 

UFH = 10 

UFDB=10 

Residential 

LOC = 1000 

Occupational 

LOC = 100 

Toxicity/Carcinogenicity 

in the rat 

LOAEL = 30.9 mg/kg/day 

based on thyroid toxicity 

(changes in thyroid 

hormone levels, 

microscopic thyroid 

changes and changes in 

thyroid weights) 

Mancozeb Inhalation Exposures 

Inhalation (Short-, 

Intermediate- or 

Long-Term) 

NOAEL = 0.079 

mg/L [equivalent 

to 21 mg/kg/day] 

UFA = 10 

UFH = 10 

UFDB=10 

Residential 

LOC = 1000 

Occupational 

LOC = 100 

Subchronic Inhalation in 

the rat 

LOAEL = 0.326 mg/L 

based on thyroid 

hyperplasia and decreased 

thyroxine (females) 

Mancozeb Cancer 

Cancer 

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)-1 to provide a 

quantitative estimate of risk. 

Table 3.3.2 Summary of Toxicological Doses and Endpoints for ETU 

Exposure/Scenario 

Point of 

Departure 

Uncertainty/

FQPA SF 

RfD, PAD, 

Level of 

Concern for RA Study & Toxic Effects 

ETU Dietary Exposures 

Acute Dietary 

(Females 13 – 49) 

NOAEL = 5 

mg/kg/day 

UFA = 10 

UFH = 10 

UFDB=10 

Acute RfD = 

0.005 mg/kg/day 

Acute PAD = 

0.005 mg/kg/day 

Developmental Toxicity 

in the rat (Khera Study, 

MRID No. 45937601) 

LOAEL = 10 mg/kg/day 

based on developmental 

defects of the brain 

Acute Dietary 

(general 

population) 

No appropriate endpoint attributable to a single exposure (dose) was identified. 

Chronic Dietary 

(all populations) 

NOAEL = 0.18 

mg/kg/day 

UFA = 10 

UFH = 10 

UFDB=10 

Chronic RfD = 

0.0002 

mg/kg/day 

Chronic PAD = 

0.0002 

mg/kg/day 

Chronic Oral Toxicity in 

the dog. 

LOAEL = 1.99 

mg/kg/day based on 

thyroid toxicity 

(increased thyroid weight 

and macroscopic changes 

in the thyroid – 

hypertrophy, follicular 

dilation) 
Mancozeb Human Health Risk Assessment D327307 & D327318

Page 19 of 62 

Table 3.3.2 Summary of Toxicological Doses and Endpoints for ETU 

Exposure/Scenario 

Point of 

Departure 

Uncertainty/

FQPA SF 

RfD, PAD, 

Level of 

Concern for RA Study & Toxic Effects 

ETU Oral Exposures 

Incidental Oral 

(Short- and 

Intermediate-Term) 

(Toddlers) 

NOAEL = 7 

mg/kg/day 

UFA = 10 

UFH = 10 

UFDB=10 

Residential LOC 

= 1000 

4 week range-finding 

dog study 

LOAEL = 34 mg/kg/day 

based on thyroid toxicity 

(decreased levels of 

thyroid hormones, gross 

thyroid lesions) 

Oral 

(Short-, and 

Intermediate-Term) 

(Females 13-49) 

NOAEL = 5 

mg/kg/day 

UFA = 10 

UFH = 10 

UFDB=10 

Residential LOC 

= 1000 

Developmental Toxicity 

in the rat (Khera Study, 

MRID No. 45937601) 

LOAEL = 10 mg/kg/day 

based on developmental 

defects of the brain 

ETU Dermal Exposures 

Dermal (Short-, 

Intermediate-Term) 

(Toddlers) 

NOAEL = 7 

mg/kg/day 

UFA = 10 

UFH = 10 

UFDB=10 

Residential LOC 

= 1000 

4 week range-finding 

dog study 

LOAEL = 34 mg/kg/day 

based on thyroid toxicity 

(decreased levels of 

thyroid hormones, gross 

thyroid lesions) 

Dermal 

(Short-, and 

Intermediate-Term) 

(Females 13-49) 

NOAEL = 5 

mg/kg/day 

 

DA = 26% 

UFA = 10 

UFH = 10 

UFDB=10 

Residential LOC 

= 1000 

Occupational 

LOC = 100 

Developmental Toxicity 

in the rat (Khera Study, 

MRID No. 45937601) 

LOAEL = 10 mg/kg/day 

based on developmental 

defects of the brain 

Dermal 

(Long-Term) 

NOAEL = 0.18 

mg/kg/day 

DA = 26% 

UFA = 10 

UFH = 10 

UFDB=10 

Residential LOC 

= 1000 

Occupational 

LOC = 100 

Chronic Oral Toxicity in 

the dog 

LOAEL = 1.99 

mg/kg/day based on 

thyroid toxicity 

(increased thyroid weight 

and macroscopic changes 

in the thyroid – 

hypertrophy, follicular 

dilation) 

ETU Inhalation Exposures 

Inhalation 

(Short-and 

Intermediate-Term) 

NOAEL = 5 

mg/kg/day 

IA = 100% 

UFA = 10 

UFH = 10 

UFDB=10 

Residential LOC 

= 1000 

Occupational 

LOC = 100 

Developmental Toxicity 

in the rat (Khera Study, 

MRID No. 45937601) 

LOAEL = 10 mg/kg/day 

based on developmental 

defects of the brain 
Mancozeb Human Health Risk Assessment D327307 & D327318

Page 20 of 62 

Table 3.3.2 Summary of Toxicological Doses and Endpoints for ETU 

Exposure/Scenario 

Point of 

Departure 

Uncertainty/

FQPA SF 

RfD, PAD, 

Level of 

Concern for RA Study & Toxic Effects 

Inhalation 

(Long-Term) 

NOAEL = 0.18 

mg/kg/day 

IA = 100% 

UFA = 10 

UFH = 10 

UFDB=10 

Residential LOC 

= 1000 

Occupational 

LOC = 100 

Chronic Oral Toxicity in 

the dog 

LOAEL = 1.99 

mg/kg/day based on 

thyroid toxicity 

(increased thyroid weight 

and macroscopic changes 

in the thyroid – 

hypertrophy, follicular 

dilation) 

ETU Cancer 

Cancer Q1

*

 = 6.01 x 10 -2

(mg/kg/day)-1

ETU is classified as a Group B2 carcinogen with a linear lowdose extrapolation approach for human risk assessment based 

on liver tumors in female mice. 

3.4 Endocrine Disruption 

EPA is required under the FFDCA, as amended by FQPA, to develop a screening 

program to determine whether certain substances (including all pesticide active and other 

ingredients) “may have an effect in humans that is similar to an effect produced by a 

naturally occurring estrogen, or other such endocrine effects as the Administrator may 

designate.” Following recommendations of its Endocrine Disruptor and Testing 

Advisory Committee (EDSTAC), EPA determined that there was a scientific basis for 

including, as part of the program, the androgen and thyroid hormone systems, in addition 

to the estrogen hormone system. EPA also adopted EDSTAC’s recommendation that the 

Program include evaluations of potential effects in wildlife. For pesticide chemicals, 

EPA will use FIFRA and, to the extent that effects in wildlife may help determine 

whether a substance may have an effect in humans, FFDCA authority to require the 

wildlife evaluations. As the science develops and resources allow, screening of 

additional hormone systems may be added to the Endocrine Disruptor Screening Program 

(EDSP). 

When additional appropriate screening and/or testing protocols being considered under 

the Agency’s EDSP have been developed, mancozeb may be subjected to further 

screening and/or testing to better characterize effects related to endocrine disruption. 

4.0 Public Health Data 

D286184, J. Blondell, 10/16/02 

HED previously reviewed incident reports in connection with the 6/3/05 human health 

risk assessment. Findings are summarized in the RED and detailed in the memorandum 

entitled Review of Mancozeb Incident Reports cited above. Briefly, eleven incidents 
Mancozeb Human Health Risk Assessment D327307 & D327318

Page 21 of 62 

were reported in the OPP Incident Data System (IDS) from 1992 to 2001 involving skin 

rashes and contact dermatitis with a few reports of dizziness and nausea. Forty four cases 

were reported in the California Pesticide illness Surveillance Program (1982 – 1999) in 

which mancozeb was judged to be responsive for the health effects reported. The 

majority of those cases involved workers developing rashes while tending grapes and 

occurred before the Special Review for mancozeb which resulting in lowering the 

application rate on grapes. 

5.0 Dietary Exposure/Risk Characterization 

5.1 Pesticide Metabolism and Environmental Degradation 

D294203; 4/3/07; C. Olinger 

D289183; 4/5/07; C. Olinger 

5.1.1 Metabolism in Primary Crops 

The qualitative nature of the residue in plants is adequately understood based on 

previously submitted plant metabolism studies with potato, soybean, sugar beet, tomato, 

and wheat. The metabolism studies indicated that the major metabolites are natural 

products (proteins, carbohydrates, lipids, and lignins) with minor amounts of mancozeb 

degradation products (ETU, ethyleneurea, ethylene bisisocyanate sulfide, Jaffe’s base, 

and ethylenediamine). 

HED has concluded that the tolerance expressions for mancozeb and the related EBDC 

active ingredients, metiram and maneb, should be revised to include residues of the 

parent EBDC only, calculated as CS2. For risk assessment purposes, both parent and 

ETU residues must be considered. 

5.1.2 Metabolism in Livestock 

The qualitative nature of the residue in livestock is adequately understood based on 

previously submitted metabolism studies with goats and poultry. The residues of concern 

in livestock commodities are the parent mancozeb and ETU. 

The residues of toxicological concern in meat and milk are mancozeb per se and ETU. 

HED has concluded that the tolerance expression for mancozeb should be revised to 

include residues of the parent EBDC only, calculated as CS2. For risk assessment 

purposes, both parent and ETU residues must be considered. 

There are no poultry feed items associated with these requested new uses; therefore, a 

discussion of poultry metabolism is not relevant to this risk assessment 
Mancozeb Human Health Risk Assessment D327307 & D327318

Page 22 of 62 

5.1.3 Rotational Crops 

A confined rotational crop study was required in the mancozeb RED and remains 

outstanding. Product labels for existing uses of mancozeb do not include any plant-back 

restrictions. HED is not requiring the study as a condition of registration to support these 

new uses for the following reasons: 

• the study was previously required in the RED 

• proposed labels are consistent with existing product labels 

• environmental fate data indicate that mancozeb is non-persistent in the 

environment (Patrick, Parker, and Ruhman, D205808, 10/20/04) 

5.1.4 Analytical Methodology 

Adequate methods are available for the enforcement of tolerances for the plant 

commodities which are the subject of this request. The Pesticide Analytical Method 

(PAM) Vol. II lists Methods I, II, III, IV, and A for the determination of dithiocarbamate 

residues in/on plant commodities. The Keppel colorimetric method (Method III) is the 

preferred method for tolerance enforcement. The Keppel method determines EBDCs as a 

group by degradation to CS2. The analytical methodology for ETU is based on the 

original method published by Olney and Yip (JAOAC 54:165-169). 

Enforcement methods for livestock commodities are not available. Prior to the RED, 

HED had concluded that tolerances were not required for animal commodities since there 

were not likely to be residues in animal commodities as a result of exposure to treated 

feed items for which there are existing tolerances. However, in the RED, HED noted that 

a new ruminant feeding study conducted at higher levels was required and the outcome of 

that study would determine if tolerances for animal commodities were required. Further, 

if tolerances are required, a method to enforce those tolerances would be required. 

The only animal feed item associated with these new uses is almond hulls. Based on the 

available feeding study, HED does not believe that there are likely to be detectable 

residues in meat and milk as a result of the proposed use on almonds, therefore; an 

enforcement method for livestock commodities is not required to support the new use on 

almonds. 

Mancozeb is not recovered through any of the FDA Multiresidue Method Testing 

Protocols. There is small recovery (<50%) of ETU using multiresidue Method 302, but 

ETU is not recovered using Methods 303 or 304. 
Mancozeb Human Health Risk Assessment D327307 & D327318

Page 23 of 62 

5.1.5 Environmental Degradation 

D290057; 10/16/02; R. Parker 

The Environmental Fate and Effects Division (EFED) provided information on the fate of 

the EBDC compounds in conjunction with the RED as part of the drinking water 

assessment for mancozeb. Mancozeb, as well as the other EBDC compounds are short 

lived in soil and water. 

 The EBDC degradate, 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 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. 

5.1.6 Pesticide Metabolites and Degradates of Concern 

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. 

Table 5.1.6 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. 

Livestock Ruminant Mancozeb & ETU Mancozeb, measured as CS2

Drinking Water ETU only Not Applicable 

5.1.7 Drinking Water Residue Profile 

D290057, 8/26/2004, R. Parker 

D323143 and 323141, 8/11/2006, M. Ruhman 

As noted above, 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 RED. It should be noted that 

the assessment conducted for the RED combined ETU from all sources of EDBC 
Mancozeb Human Health Risk Assessment D327307 & D327318

Page 24 of 62 

pesticides, including mancozeb. After consideration of the new application rates and use 

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

most recent drinking water assessment, 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 uses on broccoli, lettuce, cabbage, pepper and almonds. 

ETU surface water estimated drinking water concentrations were based both on PRZMEXAMS 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, 

6/3/2005, 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 cited 

above. 

ETU estimated drinking water concentrations provided by EFED are summarized below. 

Table 5.1.7 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. 
Mancozeb Human Health Risk Assessment D327307 & D327318

Page 25 of 62 

5.1.8 Food Residue Profile 

D294203; 4/3/07; C. Olinger 

D289183; 4/5/07; C. Olinger 

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

uses that are the subject of these two petitions, 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. 

Broccoli 

Previously submitted data for broccoli (D198104, 9/6/96, R. Perfetti) represented three 

trials conducted in Zone 10 (CA) in which broccoli was harvested 7 days following the 

last of six applications of the 75% DF formulation at 1.3-1.9 lb ai/A/application for a 

total seasonal rate of ~9.6 lb ai/A. Applications were made with 7- to 10-day retreatment 

intervals (RTIs). Residues of mancozeb were 1.43 ppm - 12.23 ppm in/on these samples. 

Additionally, five broccoli field trials were conducted in the United States in Zones 6 

(TX; 1 trial), 10 (CA; 3 trials), and 12 (OR; 1 trial) during the 1997 growing season. 

Maximum residues of mancozeb and ETU were, respectively, 2.65 ppm and 0.014 ppm 

in/on broccoli harvested 7-8 days following foliar treatment with the 75% DF formulation 

at a total rate of 9.4-9.7 lb ai/A. 

The current broccoli crop field trial data in combination with the previously submitted 

crop field trial data are adequate to satisfy data requirements and support use of the WP 

and DF formulations of mancozeb on broccoli. The available crop field trial data support 

a tolerance for residues of mancozeb, expressed in terms of CS2, in/on broccoli at 7.0 

ppm. 

Head Lettuce 

Previously submitted data represented 6 trials conducted in CA (3 trials) and FL (3 trials). 

Head lettuce grown in CA was harvested 10 days following the last of 4 applications of 

the 75% DF formulation at 1.6 lb ai/A/application for a total application rate of 6.4 lb 

ai/A (1x the proposed maximum seasonal rate to lettuce grown in CA). Head lettuce 

grown in FL was harvested 10 days following the last of 6 applications of the 75% DF or 

80% WP formulation at 1.5-1.6 lb ai/A/application for total application rates of 9.5-9.6 lb 

ai/A (~1x the proposed maximum seasonal rate to lettuce grown in states other than CA). 

Applications were made with 6- to 10-day retreatment intervals (RTIs). Residues of 

mancozeb were 0.47-3.87 ppm in/on untrimmed head lettuce

Dow AgroSciences (as Rohm and Haas Company) has submitted field trial data for 

mancozeb on head lettuce. Two lettuce field trials were conducted in the United States in 

Zone 10 (CA) during the 1997 growing season. Maximum residues of mancozeb and 

ETU were, respectively, 0.608 ppm and 0.0085 ppm in/on head lettuce harvested 10 days 

following foliar treatment with the 4 lb/gal flowable concentrate formulation at a total 

rate of 9.6 lb ai/A. 
Mancozeb Human Health Risk Assessment D327307 & D327318

Page 26 of 62 

The submitted head lettuce crop field trial data combined with supporting information 

from the leaf lettuce data, are sufficient to establish a tolerance and to support the use of 

the WP and DF formulations on head lettuce. The available crop field trial data would 

support a tolerance for residues of mancozeb, expressed in terms of CS2, in/on head 

lettuce at 3.5 ppm. 

Leaf Lettuce

Three lettuce field trials were conducted in the United States in Zones 1 (NY; 1 trial), 3 

(FL; 1 trial), and 10 (CA; 1 trial) during the 1997 growing season. Maximum residues of 

mancozeb and ETU were, respectively, 10.2 ppm and 0.14 ppm in/on leaf lettuce 

harvested 10-11 days following foliar treatment with the 75% DF formulation at a total 

rate of 9.4-9.7 lb ai/A. Maximum residues of mancozeb and ETU were, respectively, 

10.67 ppm and 0.058 ppm in/on leaf lettuce harvested 14-15 days following treatment. 

Five lettuce field trials were conducted in the United States in Zone 10; three trials were 

located along the coast (Monterey and Ventura Counties) and two trials were located in 

the Central Valley (Tulare and Madera Counties) in CA. The trials were conducted 

during the 1999 growing season. Maximum residues of mancozeb and ETU were, 

respectively, 108 ppm and 0.600 ppm in/on leaf lettuce harvested 10 days following 

foliar treatment with the 75% DF formulation at a total rate of 6.4-6.6 lb ai/A. Maximum 

residues of mancozeb and ETU were, respectively, 97.4 ppm and 0.785 ppm in/on leaf 

lettuce harvested 14 days following treatment. Maximum residues of mancozeb and ETU 

were, respectively, 267 ppm and 0.385 ppm in/on leaf lettuce harvested 10 days 

following foliar treatment with the 4 lb/gal FlC (flowable concentrate) formulation at a 

total rate of 6.4 lb ai/A. Maximum residues of mancozeb and ETU were, respectively, 

148 ppm and 0.694 ppm in/on leaf lettuce harvested 14 days following treatment. The 

petitioner noted that residues in/on leaf lettuce from the Madera County field trial 

(#98299-5) were much higher (>3x) than those in/on samples from the other CA field 

trials, most likely because of the method of application. At the Madera County trial, 

applications were made using a U-shaped boom, which applies the test substance around 

the whole plant including the underside of the leaves not typically exposed to sunlight 

and moisture. In addition, the Central Valley area of CA is typically hotter and drier than 

other areas of CA, and the highest residues were observed in/on samples from the two 

trials conducted in the Central Valley. 

The submitted leaf lettuce crop field trial data are adequate to satisfy data requirements to 

support use of the WP or DF formulations on leaf lettuce. Because the maximum 

observed residues in/on head lettuce and leaf lettuce differ by more than 5x, the petitioner 

must propose separate tolerances for head lettuce and leaf lettuce. The available crop 

field trial data would support a tolerance for residues of mancozeb, expressed in terms of 

CS2, in/on leaf lettuce at 18 ppm, provided that the label is modified to prohibit the use of 

a “U-shaped” boom. 

Pepper 

Previously submitted data for pepper (DP Barcode D198104, 9/6/96, R. Perfetti) 

represented two trials conducted in CA and FL. At the CA trial, peppers were harvested 

7 days following the last of six applications of the 75% DF formulation at 1.6 lb 
Mancozeb Human Health Risk Assessment D327307 & D327318

Page 27 of 62 

ai/A/application for a total seasonal rate of 9.6 lb ai/A (1x the proposed maximum 

seasonal rate to peppers grown west of the Mississippi River). At the FL trial, peppers 

were harvested 10 days following the last of six applications of the 80% WP formulation 

at 2.4 lb ai/A/application for a total seasonal rate of 14.4 lb ai/A (1x the proposed 

maximum seasonal rate to peppers grown east of the Mississippi River). Applications 

were made with 7- to 10-day RTIs. Residues of mancozeb were 0.48 and 1.02 ppm in/on 

these samples. 

Nine pepper field trials were conducted in the United States; six trials were conducted on 

bell pepper in Zones 2 (GA and SC; 2 trials), 3 (FL; 1 trial), 5 (OH; 1 trial), 6 (OK; 1 

trial), and 10 (CA; 1 trial), and three trials were conducted on non-bell pepper in Zones 1 

(NY; 1 trial), 8 (NM; 1 trial), and 10 (CA; 1 trial) during the 1997 growing season. 

For locations west of the Mississippi River, maximum residues of mancozeb and ETU 

were, respectively, 5.95 ppm and 0.04 ppm in/on bell pepper, and 10.0 ppm and 0.09 ppm 

in/on non-bell pepper harvested 7 days following foliar treatment with the 75% DF 

formulation at a total rate of 9.3-9.6 lb ai/A. For locations east of the Mississippi River, 

maximum residues of mancozeb and ETU were, respectively, 1.90 ppm and 0.06 ppm 

in/on bell pepper, and 1.87 ppm and 0.02 ppm in/on non-bell pepper harvested 7 days 

following foliar treatment with the 75% DF formulation at a total rate of 14.2-14.7 lb 

ai/A. For locations west of the Mississippi River, maximum residues of mancozeb and 

ETU were, respectively, 2.13 ppm and 0.03 ppm in/on bell pepper, and 10.1 ppm and 

0.03 ppm in/on non-bell pepper harvested 7 days following foliar treatment with the 4 

lb/gal FlC formulation at a total rate of 9.6-9.7 lb ai/A. For locations east of the 

Mississippi River, maximum residues of mancozeb and ETU were, respectively, 5.37 

ppm and 0.05 ppm in/on bell pepper harvested 7 days following foliar treatment with the 

4 lb/gal FlC formulation at a total rate of 14.2-14.6 lb ai/A. No non-bell pepper trials 

were conducted east of the Mississippi River with the 4 lb/gal FlC formulation. 

The current pepper crop field trial data in combination with the previously submitted crop 

field trial data are adequate to satisfy geographic representation data requirements for use 

of the WP or DF formulations on pepper. The available crop field trial data would 

support a tolerance for residues of mancozeb, expressed in terms of CS2, in/on pepper at 

12 ppm. 

Cabbage 

Previously submitted data for cabbage (D198104, 9/6/96, R. Perfetti) represented 9 trials 

conducted in CA, FL, MI, NC, NJ, NY, OH, TX, and WI in which cabbage was treated 

with 6 applications of the 75% DF or 80% WP formulation at 1.5-1.8 lb ai/A/application 

for total application rates of 9.5-9.7 lb ai/A (~1x the proposed maximum seasonal rate). 

Applications were made with 6- to 11-day RTIs, and samples were harvested 10 days 

after treatment in FL and 7 days after treatment in all other states. Residues of mancozeb 

were 0.64-10.74 ppm in/on untrimmed cabbage. 

The available data are adequate to satisfy geographic representation requirements and 

support establishment of a tolerance for the use of the WP or DF formulations on 
Mancozeb Human Health Risk Assessment D327307 & D327318

Page 28 of 62 

cabbage. The data would support a tolerance for residues of mancozeb, expressed in 

terms of CS2, in/on cabbage at 9.0 ppm. 

Almonds 

Previously, the petitioner had submitted crop field trial data for almonds reflecting five 

field trials conducted in CA (MRID 43018401; DP Barcodes D201278 and D206514, 

9/16/94, R. Perfetti); at each trial, almonds were treated with 3 applications of the 80% 

WP or 75% DF formulation at 4.8 lb ai/A/application, with retreatment intervals of 8-19 

days, for a total seasonal rate of 14.4 lb ai/A (1x the proposed maximum seasonal rate). 

Samples were harvested 136-161 days following the final application and were stored 

frozen for 238-285 days (7.8-9.4 months) prior to analysis. Residues of mancozeb and 

ETU were below the LOQ (<0.05 and <0.01 ppm, respectively) in/on all samples of 

almond nutmeat, and were 4.64-5.98 ppm and 0.107-0.471 ppm, respectively, in/on 

almond hulls. 

Dow AgroSciences (as Rohm and Haas Company) has submitted field trial data for 

mancozeb on almonds. Six almond field trials were conducted in the United States in 

Zone 10 (CA) during the 1996 growing season. Each field test consisted of one untreated 

plot and four treated plots. Six or seven foliar spray applications of a 75% DF 

formulation of mancozeb were made to almond trees at ~6.4 lb ai/A/application for a 

total rate of ~38.4 or ~44.8 lb ai/A (2.7x or 3.1x the proposed maximum seasonal rate for 

almonds). Applications were started at the popcorn to full bloom growth stage, and 

subsequent applications were made at 14- to 33-day retreatment intervals; at most trials, 

all applications except the first one or two were made postbloom. Applications were 

made using ground equipment. Two plots were treated with concentrate spray volumes 

(<50 gal/A) and two plots were treated with dilute spray volumes (>100 gal/A); an 

adjuvant was added to all of the spray mixtures. Samples of almonds were harvested 15-

17 days after the last application (DALA) from one dilute and one concentrate treated 

plot, and samples of mature almonds were harvested 59-60 DALA from the other 

concentrate and dilute treated plots. Almonds were separated into nutmeats and hulls. 

No significant differences were observed in the mancozeb and ETU residues in/on 

almond nutmeat and hulls harvested 59-60 days following foliar applications made with 

concentrate (<50 gallons per acre (GPA)) versus dilute (>100 GPA) spray volumes in 

exaggerated rate studies. Using concentrate spray volumes, the maximum residues of 

mancozeb and ETU, respectively, were 0.163 ppm and <0.01 ppm (LOQ) in/on nutmeat, 

and 38.6 ppm and 1.55 ppm in/on almond hulls. Using dilute spray volumes, the 

maximum residues of mancozeb and ETU, respectively, were 0.129 ppm and <0.01 ppm 

(LOQ) in/on nutmeat, and 32.9 ppm and 1.05 ppm in/on almond hulls. Overall, the 

maximum residues of mancozeb and ETU, respectively, were 0.163 ppm and <0.01 ppm 

in/on almond nutmeat, and 38.6 ppm and 1.55 ppm in/on almond hulls. No significant 

differences were observed in the mancozeb and ETU residues in/on almond nutmeat and 

hulls harvested 15-17 days following foliar applications made with concentrate (<50 

GPA) versus dilute (>100 GPA) spray volumes. Using concentrate spray volumes, the 

maximum residues of mancozeb and ETU, respectively, were 0.117 ppm and <0.01 ppm 
Mancozeb Human Health Risk Assessment D327307 & D327318

Page 29 of 62 

(LOQ) in/on nutmeat, and 49.0 ppm and 1.32 ppm in/on almond hulls. Using dilute 

spray volumes, the maximum residues of mancozeb and ETU, respectively, were 0.133 

ppm and <0.01 ppm (LOQ) in/on nutmeat, and 47.9 ppm and 1.48 ppm in/on almond 

hulls. Overall, the maximum residues of mancozeb and ETU, respectively, were 0.133 

ppm and <0.01 ppm in/on almond nutmeat, and 49.0 ppm and 1.48 ppm in/on almond 

hulls. In general, residues of mancozeb and ETU in/on nutmeat and hull samples 

harvested at the 15- to 17-day PHI declined (or remained below the LOQ) at the 59/60-

day PHI. 

HED concludes that adequate crop field trial data have been submitted to support the 

proposed use of mancozeb on almonds. The available data would support a tolerance for 

residues of mancozeb, expressed in terms of CS2, in/on almond nutmeat at 0.03 ppm 

(LOQ) and almond hulls at 4.0 ppm. 

5.1.9 International Residue Limits 

There are no established or proposed Codex maximum residue limits for residues of 

mancozeb per se; however, Codex limits for dimethyldithiocarbamates fungicides are 

grouped under dithiocarbamates. Codex MRLs for dithiocarbamates have been 

established for the following commodities: head cabbages at 5 ppm (based on mancozeb 

and maneb data); Cos lettuce at 10 ppm (based on maneb data); head lettuce at 10 ppm 

(based on mancozeb, maneb, and metiram data); sweet peppers at 1 ppm (based on 

mancozeb and maneb data); almonds at 0.1 ppm and almond hulls at 20 ppm (based on 

maneb and ziram data). The MRLs are currently expressed as ppm CS2. Canadian 

MRLs have been established for ethylenebisdithiocarbamate fungicides and are expressed 

in terms of manganese and zinc ethylenebis (dithiocarbamate) (polymeric); MRLs have 

been established for broccoli, cabbage, lettuce, and peppers at 7 ppm. No Mexican 

MRLs have been established for residues of mancozeb in the requested crops. 

HED has recommended that all tolerances for the EBDC pesticides be expressed in terms 

of CS2, therefore, harmonizing the tolerance definition with the Codex tolerance 

expression. However, for the reasons indicated below, the recommended tolerance levels 

are not harmonized with Codex. 

• Based on the calculations in the tolerance spreadsheet, the appropriate tolerance 

level for cabbage is 9.0 ppm. The tolerance level cannot be harmonized with 

Codex; the highest residue level in the crop field trials (6.0 ppm in CS2

equivalents) is greater than the Codex MRL for cabbage. 

• The available data indicate that the appropriate tolerance level for head lettuce is 

3.5 ppm. The tolerance level cannot be harmonized with Codex; the highest 

residue level in the crop field trials (2.2 ppm in CS2 equivalents) is considerably 

less than the Codex MRL of 10 ppm for head lettuce. 
Mancozeb Human Health Risk Assessment D327307 & D327318

Page 30 of 62 

• The available data indicate that the appropriate tolerance level for leaf lettuce is 

18 ppm. The tolerance level cannot be harmonized with Codex; the highest 

residue level in the crop field trials (14 ppm in CS2 equivalents) is greater than the 

Codex MRL for Cos lettuce. 

• The appropriate tolerance level for pepper is 12 ppm. The tolerance level cannot 

be harmonized with Codex as the Codex MRL has been established for sweet 

pepper only. 

• The appropriate tolerance level for almond hulls is 4 ppm. This value can not be 

harmonized with Codex as it is significantly below the Codex MRL of 20 ppm. 

5.2 Dietary Exposure and Risk 

D323878 and D323879, 4/17/07, C. Olinger

Acute and chronic dietary risk assessments for mancozeb and acute, chronic and cancer 

dietary risk assessments for mancozeb-derived ETU were conducted using the Dietary 

Exposure Evaluation Model (DEEM-FCIDTM, Version 2.03) which uses food 

consumption data from the U.S. Department of Agriculture’s Continuing Surveys of 

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

The acute, chronic, and cancer assessments can be considered somewhat refined. 

Residue estimates were refined using consumer processing factors (washing, cooking), 

commercial processing, percent crop treated factors, and monitoring data for several 

commodities. Crop field trial data were used for all of the proposed new uses and several 

existing uses, which are likely to provide higher estimates than actual exposures. 

Since mancozeb per se is not expected in ground or surface water, the acute and chronic 

exposure and risk assessments for the parent compound consider contribution from food 

residues only. Additionally, since 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 to provide a quantitative estimate of risk. 

Details of the dietary exposure and risk assessment are contained in the memorandum 

entitled PP#4F4324 and 4F4333 Mancozeb Acute, Chronic and Cancer Dietary 

Exposure Assessments for New Tolerances on Almonds, Broccoli, Cabbage, Lettuce and 

Peppers, which is referenced above. 

5.2.1 Acute Dietary Exposure/Risk 

A probabilistic acute dietary exposure and risk analysis was conducted for both 

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

mancozeb. Maximum estimated percent crop treated information for the existing uses, as 
Mancozeb Human Health Risk Assessment D327307 & D327318

Page 31 of 62 

well as maximum projected percent crop treated information for the new uses were 

incorporated into the acute dietary assessments. For commodities which are considered 

partially blended, or not blended, the entire distributions of residue data from field trials 

or monitoring data from a market basket survey were used to generate residue 

distribution files (RDFs). Where HED had only field trial data for a partially blended or 

non blended commodity, the adjustment for percent crop treated is incorporated into the 

RDF via addition of zero residue values corresponding to the percent of crop not treated. 

For partially blended or not blended commodities where monitoring data from a market 

basket survey are available, the maximum percent crop treated data were used to 

determine what percent of the non-detects should be treated as zeros and what percentage 

should be incorporated into the RDF as half the limit of quantitation (1⁄2 LOQ). The only 

exception is the wine RDF which used the entire distribution of monitoring data with no 

further adjustment for percent of crop treated. For commodities considered to be blended 

where either field trial data or monitoring data were available, the average residue 

incorporating the likely maximum estimated percent crop treated was used as a point 

estimate. Processing and cooking factors from studies with mancozeb as well as with the 

other EBDC pesticides were incorporated into the analysis. 

An acute endpoint was selected for the subpopulation, females 13 – 49 years of age only. 

No acute endpoint was selected for the general population. For mancozeb per se, females 

13 – 49 years of age have an exposure from food that is equivalent to an estimated risk of 

6.9% of the mancozeb aPAD at the 99.9th percentile. HED is not concerned with risks 

that do not exceed 100% of the aPAD, therefore; HED has no concern for acute risks to 

females 13 – 49 yrs, the subgroup of concern, resulting from exposure to mancozeb per 

se from the existing and new uses of mancozeb. 

 

For mancozeb-derived ETU, females 13 – 49 yrs of age have an exposure from food only 

that is equivalent to 24% of the ETU aPAD at the 99.9th percentile. For mancozebderived ETU, females 13 – 49 years of age have an exposure from food and water that is 

equivalent to 71% of the ETU aPAD at the 99.9th percentile. HED is generally not 

concerned with risks that do not exceed 100% of the aPAD, therefore; HED has no 

concern for acute risks to females 13 – 49 yrs, the subgroup of concern, resulting from 

exposure to mancozeb-derived ETU through food and water resulting from the existing 

and new uses of mancozeb. 

Exposures and risks for both mancozeb and mancozeb-derived ETU at select percentiles 

are summarized in Table 5.2.1, below. 
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Table 5.2.1 Results of Acute Dietary Exposure and Risk Assessment for Mancozeb 

and ETU 

95th Percentile 99th Percentile 99.9th Percentile 

Population 

Subgroup 

aPAD 

(mg/kg/day) Exposure 

(mg/kg/day) 

% 

aPAD 

Exposure 

(mg/kg/day) 

% 

aPAD 

Exposure 

(mg/kg/day) 

% 

aPAD 

Mancozeb 

Females 

13 – 49 yrs 

Food Only

0.13 0.000216 0.17 0.0126 0.97 0.008926 6.9 

ETU 

Females 

13 - 49 yrs 

Food Only 

0.005 0.0001 2.0 0.000351 7.0 0.00123 24 

Females 

13 - 49 yrs 

Food and 

Water 

0.005 0.00128 26 0.0021 42 0.00356 71 

5.2.2 Chronic Dietary Exposure/Risk 

Chronic anticipated residues were calculated from field trial or monitoring data for 

mancozeb and ETU. Averages of the field trial residue values were used for the new 

tolerances, while either field trial or market basket survey data were used for established 

uses. Both average percent crop treated information for the existing uses as well as 

estimates of average projected percent crop treated for the new uses were incorporated 

into the chronic dietary risk assessments. Additionally, residue estimates were further 

refined using consumer processing factors (washing, cooking) and commercial 

processing factors. 

For mancozeb per se, the general U.S. population has an estimated exposure from food 

that is equivalent to 1.5% of the mancozeb cPAD. The most highly exposed subgroup is 

children 1 – 2 years of age with an estimated exposure from food that is equivalent to 

3.3% of the mancozeb cPAD. HED is generally not concerned with risks that do not 

exceed 100% of the cPAD, therefore; HED has no concern for chronic risks to the 

general population or any regulated subgroup, resulting from exposure to mancozeb per 

se from the existing and new uses of mancozeb. 

For mancozeb-derived ETU, the general U.S. population has an estimated exposure from 

food only that is equivalent to 14% of the ETU cPAD. The most highly exposed 

subgroup is children 1 – 2 years of age with an estimated exposure from food that is 

equivalent to 32% of the ETU cPAD. For mancozeb-derived ETU, the general 

population has an estimated exposure from food and water that is equivalent to 16% of 

the ETU cPAD. The most highly exposed subgroup is children 1 – 2 years of age with an 
Mancozeb Human Health Risk Assessment D327307 & D327318

Page 33 of 62 

estimated exposure from food that is equivalent to 36% of the ETU cPAD. HED is 

generally not concerned with risks that do not exceed 100% of the cPAD, therefore; HED 

has no concern for chronic risks to the general population or any regulated subgroup, 

resulting from dietary exposure to mancozeb-derived ETU from the existing and new 

uses of mancozeb. 

Chronic dietary exposures and risks for both mancozeb and mancozeb-derived ETU for 

the U.S. population and all regulated subgroups are summarized in Tables 5.2.4.1, 5.2.4.2 

and 5.2.4.3, below. 

5.2.3 Cancer Dietary Risk 

Cancer anticipated residues were calculated from either field trial or monitoring data for 

mancozeb-derived ETU. Averages of the field trial residue values were used for the new 

tolerances, while field trial or market basket survey data were used for established uses. 

Both average percent crop treated information for the existing uses as well as estimates of 

average projected percent crop treated information for the new uses were incorporated 

into the cancer dietary risk assessment. Additionally, residue estimates were further 

refined using consumer processing factors (washing, cooking) and commercial 

processing factors. 

 Exposure and risk estimates for the ETU cancer assessment are presented in Tables 

5.2.4.2 and 5.2.4.3, below. Because of the uncertainties regarding estimation of cancer 

potency and human exposure, risk estimates ranging from 1 x10-6 to 3 x10-6 are generally 

considered indistinguishable. The estimated cancer risk for food alone and aggregated 

food and water are within this range and are not of concern. 

5.2.4 Summary of Dietary Exposure and Risk for Mancozeb and ETU 

Tables 5.2.4.1, 5.2.4.2 and 5.2.4.3 provide a summary of the dietary exposure and risk for 

mancozeb and mancozeb-derived ETU. 

Table 5.2.4.1 Summary of Dietary Exposure and Risk for Mancozeb 

Food Only

Acute Dietary 

(99.9th Percentile) Chronic Dietary Cancer 

Population Subgroup 

Dietary 

Exposure 

(mg/kg/day) % aPAD 

Dietary 

Exposure 

(mg/kg/day) % cPAD 

Dietary 

Exposure 

(mg/kg/day) Risk 

General U.S. Population 0.000073 1.5 

All Infants (< 1 year old) 

N/A 

0.000058 1.2 

Mancozeb’s potential for 

carcinogenicity is due to 

the formation of the 
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Table 5.2.4.1 Summary of Dietary Exposure and Risk for Mancozeb 

Food Only

Acute Dietary 

(99.9th Percentile) Chronic Dietary Cancer 

Population Subgroup 

Dietary 

Exposure 

(mg/kg/day) % aPAD 

Dietary 

Exposure 

(mg/kg/day) % cPAD 

Dietary 

Exposure 

(mg/kg/day) Risk 

Children 1-2 years old 0.000167 3.3 

Children 3-5 years old 0.0000133 2.7 

Children 6-12 years old 0.00008 1.6 

Youth 13-19 years old 0.000051 1.0 

Adults 20-49 years old 0.000068 1.4 

Adults 50+ years old 0.000066 1.3 

Females 13-49 years old 0.008926 6.9 0.000071 1.4 

metabolite ETU which is 

classified as a probable 

human carcinogen (B2). 

Mancozeb’s cancer risk is 

calculated by estimating 

exposure to mancozebderived ETU and using 

the ETU cancer potency 

factor (Q1

*

) of 6.01 x 10 -2

(mg/kg/day)-1 to provide a 

quantitative estimate of 

risk. 

Table 5.2.4.2 Summary of Dietary Exposure and Risk for Mancozeb-Derived ETU 

Food Only

Acute Dietary 

(99.9th Percentile) Chronic Dietary Cancer 

Population Subgroup 

Dietary 

Exposure 

(mg/kg/day) % aPAD 

Dietary 

Exposure 

(mg/kg/day) % cPAD 

Dietary 

Exposure 

(mg/kg/day) Risk 

General U.S. Population 0.000028 14 0.000028 1.7 x 10-6

All Infants (< 1 year old) 0.000028 14 

Children 1-2 years old 0.00065 32 

Children 3-5 years old 0.000051 26 

Children 6-12 years old 0.000033 16 

Youth 13-19 years old 0.000019 9.5 

Adults 20-49 years old 0.000025 12 

Adults 50+ years old 

N/A 

0.000025 13 

Females 13-49 years old 0.00123 24 0.000024 12 

N/A 
Mancozeb Human Health Risk Assessment D327307 & D327318

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Table 5.2.4.3 Summary of Dietary Exposure and Risk for Mancozeb-Derived ETU 

Food and Water

Acute Dietary 

(99.9th Percentile) Chronic Dietary Cancer 

Population Subgroup 

Dietary 

Exposure 

(mg/kg/day) % aPAD 

Dietary 

Exposure 

(mg/kg/day) % cPAD 

Dietary 

Exposure 

(mg/kg/day) Risk 

General U.S. Population 0.000032 16 0.000032 1.9 x 10-6

All Infants (< 1 year old) 0.000042 21 

Children 1-2 years old 0.000071 36 

Children 3-5 years old 0.000057 29 

Children 6-12 years old 0.000037 18 

Youth 13-19 years old 0.000022 11 

Adults 20-49 years old 0.000029 14 

Adults 50+ years old 

N/A 

0.000030 15 

Females 13-49 years old 0.00356 71 0.000028 14 

N/A 

 

6.0 Residential (Non-Occupational) Exposure/Risk Characterization 

D317368, 05/31/05, T. Dole 

No new residential uses are being added to the mancozeb label as a result of this action, 

however there are existing residential uses registered. 

The document entitled Mancozeb: 2nd Revised Occupational and Residential Exposure 

Assessment and Recommendations for the Reregistration Eligibility Decision Document

cited above provides a detailed summary of the exposure and risk assessment for the 

existing residential uses of mancozeb. Subsequent to the completion of that 

memorandum, the EBDC Team, revisited the toxicological data requirements for 

mancozeb and concluded that a DNT was required and that a database uncertainty factor 

to account for the lack of that study should be applied to the mancozeb risk assessments. 

As a result of that decision, the level of concern for the residential risk assessments was 

revised from 100 to 1000. 

All residential exposure scenarios previously evaluated had MOEs that were above the 

LOC of 1000, with the exception of incidental oral risks for toddlers exposed to 

transplanted turf treated on a sod farm with a PHI of 3 day. Based on the current LOC, a 

PHI of 5 days would be required to assure that incidental oral risks to toddlers exceeded 

an LOC of 1000. 
Mancozeb Human Health Risk Assessment D327307 & D327318

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Exposures and risks from the various residential scenarios are briefly summarized here 

since those values are required for the aggregate risk assessment to support the new uses 

that are the subject of this action. 

6.1 Residential Handler Exposures and Risks

The existing residential handler scenario identified for mancozeb is for the application of 

mancozeb in home gardens. The anticipated use patterns and current labeling indicate 

that backpack and low pressure handwand sprayers could be used by the homeowner to 

make mancozeb applications. Residential risks are assumed to be of short-term and 

intermediate-term in duration for home garden scenarios and for adults on treated turf. 

Residential scenarios are considered to be of short-term duration for toddlers on treated 

turf since it is unlikely that sod would be installed more than once per year and since 

subsequent to installation, turf is watered which would contribute to a more rapid 

dissipation of residues. There are no long-term residential exposure scenarios associated 

with mancozeb at this time. 

Since the endpoints selected for the short- and intermediate-term assessment are identical, 

short- and intermediate-term risk assessments yield the same MOEs and a single value is 

shown in the tables below. Risks from both mancozeb and mancozeb-derived ETU are 

calculated. Based on tank mix studies, it was assumed that 0.2% of the mancozeb would 

convert to ETU, additionally; a 7.5% in vivo conversion of mancozeb to ETU was also 

considered in the exposure calculations. 

Mancozeb 

A mancozeb dermal risk assessment is not required since a dermal endpoint was not 

selected based on lack of systemic toxicity at the limit dose of 1000 mg/kg/day in the 28-

day dermal toxicity study. Inhalation exposure and risks were calculated for residential 

handlers applying mancozeb by either backpack sprayer or low pressure handwand 

sprayer. For both scenarios, inhalation MOEs far exceeded the level of concern of 1000 

for mancozeb; therefore, HED has no concern for short- and intermediate-term inhalation 

risks from mancozeb per se to residential handlers from the existing home garden use. 

Short/Intermediate-term inhalation exposures and risks for mancozeb per se are 

summarized in Table 6.1.1, below. 

Table 6.1.1 Home Gardener Handler Exposure and Short/Intermediate-Term Risks for 

Mancozeb

Exposure Scenario

Application Rate 

(lb ai/acre)

Area Treated 

(Acre/Day)

Absorbed Daily 

Dose (mg/kg/day)

Inhalation 

MOE1

Backpack 2.4 x 10-5 890000 

Low Pressure 

Handwand 

2.4 0.023 

(1000 ft2

) 7.1 x 10-6 3000000 

1 NOAEL is 21 mg/kg/day; 100% IA. 
Mancozeb Human Health Risk Assessment D327307 & D327318

Page 37 of 62 

ETU

Both dermal and inhalation exposures and risks for mancozeb-derived ETU were 

calculated for residential handlers. Since the short/intermediate-term dermal and 

short/intermediate-term inhalation endpoints were taken from the same study, dermal and 

inhalation exposures were added to calculate a combined absorbed mancozeb-derived 

ETU daily dose. That dose was then compared to the NOAEL from the rat 

developmental toxicity study. Short/intermediate-term combined dermal and inhalation 

risks for residential handlers using both backpack sprayers and low pressure handwand 

sprayers far exceeded the LOC of 1000; therefore, HED has no concern short- and 

intermediate-term risks to residential handlers exposed to mancozeb-derived ETU. 

Short- and intermediate-term dermal and inhalation exposures and combined risk for 

residential handlers are summarized in Table 6.1.2, below. 

Table 6.1.2 Home Gardener Handler Exposure and Short/Intermediate-Term Risks for 

Mancozeb-Derived ETU

Absorbed ETU Daily Dose 

Exposure Scenario (mg/kg/day)

Dermal Inhalation

Combined Absorbed ETU 

Daily Dose (mg/kg/day)

ETU 

MOE1 

Backpack 5.9 x 10-6 2.1 x 10-6 8.1 x 10-6 620000 

Low Pressure 

Handwand 4.4 x 10-5 6.4x 10-7 4.5 x 10-5 110000 

1 NOAEL is 5 mg/kg/day

Cancer

Residential handler estimated cancer risks were calculated for applicators using a 

backpack sprayer and a low pressure handwand sprayer. For applicators using backpack 

sprayers the estimated cancer risk from mancozeb-derived ETU was 4.1 x 10-9. 

Residential handlers using low pressure handwand sprayers had an estimated cancer risk 

of 2.3 x 10-8. 

HED has no concern for cancer risks to residential handlers as a result of exposure to 

mancozeb-derived ETU from the existing home garden use. Cancer risks for home 

garden handlers are summarized in the table below. 
Mancozeb Human Health Risk Assessment D327307 & D327318

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Table 6.1.3 Home Garden Handler Exposure and Cancer Risk for ETU from Mancozeb

Exposure Scenario 

Application 

Rate 

(lbs ai/acre)

Absorbed Daily 

Dose (mg/kg/day)a

Lifetime 

Average Daily 

Doseb Cancer Riskc

Backpack 2.4 6.9 x 10-6 6.8 x 10-8 4.1 x 10-9

Low Pressure 

Handwand 2.4 3.7 x 10-5 3.8 x 10-7 2.3 x 10-8

Notes 

a. ADD = Absorbed Daily Dose from dermal and inhalation exposure 

b. LADD = Lifetime Average Daily Dose = ADD * (5 exposure day per year/365 days per year)*(50 years of 

exposure/70 years of life) 

c. LADD * Q1* where Q1* = 0.0601 mg/kg/day 

6.2 Residential Postapplication Exposure

Mancozeb can be used in areas that can be frequented by the general population including 

residential areas (e.g., home lawns and gardens) and golf courses. As a result, individuals 

can be exposed by entering these areas if the areas have been previously treated. The 

residential postapplication exposure and risk assessments conducted included the 

following: 

• adult dermal exposure from contact with treated home gardens

• adult dermal exposure from contact with treated turf (golfer scenario)

• youth (ages 10 – 12) dermal exposure from working in treated home gardens

• toddler’s incidental oral exposure from hand-to-mouth transfer of residues, objectto-mouth transfer of residues and soil ingestion from contact with treated turf

• toddler dermal exposure from contact with treated turf.

The residential postapplication exposure and risk assessments are detailed in the 5/31/05 

ORE (occupational and residential exposure) memorandum cited under section 6.0. 

Results of the residential postapplication exposure and risk assessment are briefly 

summarized below. 

6.2.1 Home Garden Postapplication Scenarios 

Mancozeb

Dermal toxicity is not expected to result from exposure to mancozeb; therefore, a dermal 

endpoint for mancozeb has not been selected. An assessment of dermal exposure and 

risk for mancozeb per se from postapplication exposure for adults and youth to treated 

home gardens is not required. 
Mancozeb Human Health Risk Assessment D327307 & D327318

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ETU

Table 6.2.1.1, below summarizes the postapplication risks from mancozeb-derived ETU 

for adults and youth exposed to treated home gardens on Day 0 (the day of application). 

Exposures are shown for low, medium and high contact activities and also for 

representative commodities that might be found in a home garden. The scenario with the 

greatest risk is shown in bold. MOEs for all scenarios for both subpopulations on Day 0 

significantly exceed the LOC of 1000 and, therefore; are not of concern. 

Table 6.2.1.1 Mancozeb-derived ETU Postapplication Short/Intermediate-Term 

Exposure and Risks for Adult and Youth Home Gardeners

ETU MOE on Day 0 (Adults/Youth)

Crop Group

Application Rate 

(lb ai/acre) Low Medium High

Very 

High

Cut Flowers 1.2 53000/97000 33000/61000 19000/35000 N/A 

 Vegetable, cucurbit - 

West 

Vegetable, cucurbit - East 

2.4 

2.4 

80000/150000 

94000/170000 

27000/49000 

31000/57000 

16000/29000*

19000/34000 

N/A 

N/A 

Vegetable, fruiting - 

West 

Vegetable, fruiting - East 

1.6 

2.4 

120000/220000 

87000/160000 

86000/160000 

62000/110000 

60000/110000 

43000/79000 

N/A 

N/A 

Low, medium and High refer to low, medium and high contact activities 

Note – while the application rates are the same for west and east cucurbit, the dislodgeable foliar residue values used for east 

and west are different, which explains the different exposures and risks from the same application rate. 

The highest exposure/risk scenario is shown in bold. 

* The adult dose for this scenario = 3.1 x 10-4 mg/kg/day and the youth dose for this scenario = 2.4 x 10-4 mg/kg/day taken 

from the ORE chapter cited above. 

Cancer

Cancer risks from exposure to mancozeb-derived ETU from home garden exposure 

scenarios are summarized in Table 6.2.1.2, below. As in the table above, the scenario 

with the highest risk is shown in bold. Cancer risks are shown for low, medium and high 

contact activities and also for representative commodities that might be found in a home 

garden. Postapplication cancer risks for adult home gardeners for all scenarios are not of 

concern. 
Mancozeb Human Health Risk Assessment D327307 & D327318

Page 40 of 62 

Table 6.2.1.2 Mancozeb-derived ETU Postapplication Cancer Risks for Adult Home 

Gardeners

Cancer Risk on Day 0 Assuming Five Exposure Days per Year 

Over a Lifetime

Crop Group

Applicatio

n Rate 

(lb ai/acre) Low* Medium* High* Very High*

Cut Flowers 1.2 4.7 x 10-8 7.5x 10-8 1.3 x 10-7 NA 

 Vegetable, cucurbit - 

West 

Vegetable, cucurbit - East 

2.4 

2.4* 

3.1 x 10-8 

2.7 x 10-8 

9.4 x 10-8 

8.0 x 10-8 

1.6 x 10-7 

1.3 x 10-7 

NA 

NA 

Vegetable, fruiting - West 

Vegetable, fruiting - East 

1.6 

2.4 

2.1 x 10-8 

2.9 x 10-8 

2.9 x 10-8 

4.1 x 10-8

4.2 x 10-8 

5.8 x 10-8 

NA 

NA 

*Note – while the application rates are the same for west and east cucurbit, the dislodgeable foliar residues for east and 

west are different, which explains the different exposures and risks from the same application rate. 

6.2.2 Treated Turf Postapplication Scenarios for Toddlers 

Toddlers can be exposed to mancozeb and its metabolite ETU when in contact with 

treated turf. Incidental oral exposures and risks are shown below. HED notes that there 

are no direct homeowner applications of mancozeb to turf; however, there is a registered 

use to permit treatment of sod on sod farms with subsequent transplantation to a 

residential setting. In calculating treated turf risks for mancozeb and its metabolite, ETU, 

HED used the outcome of the RED risk mitigation negotiations which provides for a 3-

day PHI and includes an additional two days for harvesting, shipment and installation for 

a total of 5 days between treatment on a sod farm and exposure in a residential setting. 

Since there are no direct home lawn uses for mancozeb, toddlers would only be exposed 

to mancozeb in a residential setting from turf transplanted from a sod farm. Since it is 

unlikely that sod would be installed more than once per year, and further since the 

installation process includes watering-in which will tend to increase the dissipation of 

residues, HED considers risks to toddlers exposed to treated lawns to be of short-term 

duration only. 

In assessing risks to toddlers from incidental oral exposure, HED sums the total exposure 

from residue transfer from hand-to-mouth, object-to-mouth and soil ingestion. 

Mancozeb

Mancozeb exposures and risks resulting from exposure to treated turf were calculated 

using a 7-day average TTR value. The dose was averaged since the effect of concern, an 

alteration of thyroid hormone, is not considered an acute affect and would not likely be 

seen after one or two days of exposure. 

The level of concern for the mancozeb incidental oral risk assessment is 1000. MOEs 
Mancozeb Human Health Risk Assessment D327307 & D327318

Page 41 of 62 

which exceed 1000 are not of concern. 

At a 3-day PHI, mancozeb MOEs for oral exposures from hand-to-mouth transfer of 

residues and for total incidental oral exposure are below 1000 and are of concern. Based 

on information on residue dissipation, HED calculates that an interval of 7 days between 

treatment and first toddler exposure to transplanted turf is required to allow residues to 

dissipate sufficiently to generate combined oral incidental risks that exceed the minimum 

required MOE of 1000 for toddlers. Assuming two days are required to harvest, ship and 

install the treated sod, a PHI of 5-days would be needed for combined incidental oral 

MOEs to exceed HED’s level of concern of 1000. Table 6.2.2.1, below shows the TTR 

values and exposures from hand-to-mouth, object-to-mouth and soil ingestion for 

toddlers exposed to residential turf from day 0 through day 13, as well as MOEs for 3-

day and 5-day PHIs. Table 6.2.2.2, below shows the combined exposures and risks for 3-

day and 5-day PHIs. 

Table 6.2.2.1 Summary of Mancozeb TTR values, Doses and MOEs at 0 to 13 Days After 

Treatment for Turf

Hand-to-Mouth3 Object-to-Mouth4 Soil Ingestion5

DAT 

TTR 

(ug/cm2) 

Dose 

(mg/kg/day) MOE 

TTR 

(ug/cm2) 

Dose 

(mg/kg/day) MOE 

TTR 

(ug/g) 

Dose 

(mg/kg/day) MOE 

Aggregate 

MOE6 

0 9.76 39.0 130.8 

1 6.60 26.4 88.4 

2 4.46 17.8 59.7 

3 3.01 12.0 40.4 

4 2.03 8.1 27.3 

5 1.37 5.5 18.4 

6 0.93 3.7 12.4 

7 0.63 2.5 8.4 

8 0.42 1.7 5.7 

9 0.29 1.1 3.8 

10 0.19 0.8 2.6 

11 0.13 0.5 1.8 

12 0.09 0.4 1.2 

13 0.06 

 

0.2 

 

0.8 

 

3-day 

PHI1 0.57 0.015 610 2.3 0.0038 2400 7.6 0.00005 180000 490 

5-day 

PHI2 0.26 0.0069 1300 1.0 0.0017 5400 3.5 0.00002 400000 1100 

1 Listed TTR value is averaged over a seven day period beginning on DAT 5 to account for a 3 day PHI and 2 days for 

 harvesting, shipping and installation.

2 Listed TTR value is averaged over a seven day period beginning on DAT 7 to account for a 5 day PHI and 2 days for 

 harvesting, shipping and installation.

3

 HTM Dose = [(TTR * Saliva extraction factor (0.5) * Surface area of hands (20 cm2) * Frequency (20 hand to 

mouth contacts per hour) * Exposure Duration (2 hours) * 0.001 mg/ug)] / [BW (15 kg)] 4

OTM Dose = [(TTR * Ingestion rate for mouthing grass (25 cm2/day) * 0.001 mg/ug)] / [BW (15 kg)] 5

Soil Ingestion Dose = [(Soil Concentration (ug/gm)* Soil ingestion rate (100 mg/day) * 0.001 mg/ug)] / [BW (15 kg)] 

6

Aggregate MOE refers to total MOE for hand-to-mouth, object-to-mouth and soil ingestion and does not include food 

residues. 
Mancozeb Human Health Risk Assessment D327307 & D327318

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Table 6.2.2.2 Summary of Mancozeb Incidental Oral Exposures and Risks for 

Toddlers Exposed to Treated Turf 

Exposure 

Pathway

3-Day PHI 

Mancozeb 

TTR* 

3-Day PHI 

Dose 

(mg/kg/day) 

3-Day PHI 

Incidental 

Oral MOE

5-Day PHI 

Mancozeb 

TTR** 

5-Day PHI 

Dose 

(mg/kg/day) 

5-Day PHI 

Incidental 

Oral MOE

Hand-toMouth 0.57

ug/cm2 0.015 610 0.26 ug/cm2

 0.0069 1300 

Object-tomouth 2.3 ug/cm2

 0.0038 2400 1.0 ug/cm2 0.0017 5400 

Soil 

Ingestion 7.6 ppm 0.00005 180000 3.5 ppm 0.00002 400000 

Total 0.019 490 0.0086 1100 

* Based on a 3-day PHI and including an additional 2 days to account for harvesting, shipping and installation, 

resulting in 5 days between treatment and residential exposure. 

** At PHI noted plus two days for harvesting/shipping/installing, MOE exceeds 1000. 

Since there were no dermal endpoints selected for mancozeb, a short-term dermal risk 

assessment for toddlers as a result of contact with treated turf is not required. 

ETU

The calculations for the ETU MOEs were not updated from the Mancozeb ORE 

Assessment for the RED (D286871 of 5/15/2003) because they indicated that there was 

no risk concern with a PHI of 3 days. 

The level of concern for the ETU incidental oral and dermal risk assessments is 1000. 

Mancozeb-derived ETU incidental oral exposures and risks to toddlers in contact with 

treated turf were calculated based on a 3-day PHI for sod farm turf. The MOE for 

combined oral incidental risk to toddlers in contact with treated turf subsequent to 

installation exceeds 1000 and is not of concern. Incidental oral exposures and risk are 

summarized in Table 6.2.2.3, below. 

Table 6.2.2.3 Summary of ETU Incidental Oral Exposures and Risks for Toddlers 

Exposed to Treated Turf

Exposure Pathway ETU TTR* Dose (mg/kg/day) MOE

Hand-to-Mouth 0.0085 ug/cm2 0.0030 2300 

Object-to-Mouth 0.034 ug/cm2 0.00075 9300 

Soil Ingestion 0.11 ppm 0.00001 700000 

Total 0.00376 1900 

* Based upon the existing PHI of 3 days and including an additional 2 days to account for harvesting, shipping and 

installation.

The short-term dermal exposures and risks for toddlers exposed to treated, transplanted 

turf are summarized in the table below. Short-term dermal risk to toddlers in contact with 

treated turf with a 3-day PHI was above 1000 and was; therefore, not of concern. 
Mancozeb Human Health Risk Assessment D327307 & D327318

Page 43 of 62 

Table 6.2.2.4 Summary of ETU Short-Term Dermal Exposures and Risks for 

Toddlers Exposed to Treated Turf

Exposure Pathway ETU TTR* Dose (mg/kg/day) MOE

Dermal 0.0085 ug/cm2 0.0022 3100 

* Based upon the existing PHI of 3 days and including an additional 2 days to account for harvesting, shipping and 

installation. 

6.2.3 Treated Turf Postapplication Scenario for Adults 

Mancozeb

The only postapplication scenario for adults in contact with treated turf is via the dermal 

route of exposure. Since no dermal endpoints were selected for mancozeb, a risk 

assessment for this scenario is not required. 

ETU

Adults may be exposed to mancozeb-derived ETU through dermal contact with turf. The 

MOE for short/intermediate-term dermal risk for the adult golfer exposed to ETU from 

contact with mancozeb treated golf courses exceeded 1000 and was; therefore, not of 

concern. Exposure and risk for adult golfers is summarized in the table below. 

 Table 6.2.3.1 ETU Short/Intermediate-Term Dermal Postapplication Risks for Adults 

Exposed to Turf

Activity

Application 

Rate 

(lb ai/acre)

Mancozeb 

TTR 

(ug/cm2)

ETU TTR 

(ug/cm2)

Transfer 

Coefficient 

(cm2/hr)

Hours per 

Day 

Exposure

ETU Dose 

(mg/kg/day) MOE

 Golf 17.4 9.76 0.060 500 4.0 0.00076 6600 

Cancer

Cancer risk to adult golfers from exposure to mancozeb-derived ETU is shown in the 

table below. Postapplication cancer risk for adult golfers is well below 3 x10-6 and is not 

of concern. 

 Table 6.2.3.2 Summary of ETU Postapplication Cancer Risks for Adults Exposed to Turf

Activity

Application 

Rate 

(lb ai/acre)

Mancozeb 

TTR 

(ug/cm2)

ETU TTR 

(ug/cm2)

Transfer 

Coefficient 

(cm2/hr)

Hours per 

Day 

Exposure

Days Per 

Year 

Exposure

Years of 

Exposure per 

Lifetime

LADD 

(mg/kg/day)

Cancer 

Risk

Golf 10.5 3.2 0.020 500 1.0 1 50 1.0 x 10-6 6 x 10-8

 

6.3 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, 
Mancozeb Human Health Risk Assessment D327307 & D327318

Page 44 of 62 

could also be a potential source of exposure from the ground 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. On a chemical by chemical basis, 

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

be placed on product labels/labeling. The Agency has completed its evaluation of the 

new database submitted by the Spray Drift Task Force, a membership of U.S. pesticide 

registrants, and is developing a policy on how to appropriately apply the data and the 

AgDRIFT computer model to its risk assessments for pesticides applied by air, orchard 

airblast and ground hydraulic methods. After the policy is in place, the Agency may 

impose further refinements in spray drift management practices to reduce off-target drift 

with specific products with significant risks associated with drift. It is noted that the 

application rate for turf was modeled to estimate postapplication residential exposure of 

toddlers. As this rate is higher than many of agricultural application rates, this scenario is 

protective of any exposure of farm children via spray drift from agricultural applications. 

7.0 Aggregate Risk Assessments and Risk Characterization 

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

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

aggregate assessment, exposures from relevant sources are added together and compared 

to quantitative estimates of hazard (e.g., a NOAEL or PAD), or the risks themselves can 

be aggregated. When aggregating exposures and risks from various sources, HED 

considers both the route and duration of exposure. 

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 result in handler exposure for 

adults and postapplication exposure to adults and youth working in the garden. The 

mancozeb turf uses result in postapplication exposure to toddlers playing on treated turf 

and adults participating in activities such as 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 they believed are likely to co-occur. 

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 
Mancozeb Human Health Risk Assessment D327307 & D327318

Page 45 of 62 

assessments. 

At the RED negotiated PHI of 3 days for sod farm use of mancozeb, incidental oral risks 

to toddlers are below the minimum required MOE of 1000; therefore since those risks are 

already of concern an aggregate risk assessment can not be conducted. HED also 

conducted an aggregate risk assessment for toddlers in contact with treated turf assuming 

an 5-day PHI, the PHI required for risks from incidental oral exposure to exceed 1000. 

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/Intermediate-Term Home Garden Aggregate (Adult) which 

considers residential handler exposures (inhalation) to adult applicators combined 

with average food exposures 

• Mancozeb Short/Intermediate-Term Treated Turf Aggregate (Toddler) which 

considers residential incidental oral exposures to toddlers combined with average 

food exposures 

• Mancozeb Long-Term (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/Intermediate-Term Home Garden Aggregate which combines handler 

exposures (inhalation and dermal) and postapplication garden exposures (dermal) 

plus food and water exposures for adults and postapplication garden exposures 

(dermal) plus food and water exposures for youth 

• ETU Short-Term Treated Turf Aggregate (Toddlers) which combines treated turf 

postapplication exposures (incidental oral and dermal) plus food and water 

exposures for toddlers 

• ETU Short/Intermediate-Term Treated Turf Aggregate (Adults “Golfers”) which 

considers short-term residential exposures (dermal) plus food and water exposures 

for adults participating in activities such as golf on treated turf 

• ETU Long-Term (Chronic, Non Cancer) Aggregate which considers exposure 

from food and water only 

• ETU Cancer Aggregate which combines handler home garden exposures (dermal 

and inhalation), postapplication home garden exposures (dermal), postapplication 

treated turf exposures (dermal) and chronic food and water for adults 
Mancozeb Human Health Risk Assessment D327307 & D327318

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7.1 Acute Aggregate Risk 

7.1.1 Mancozeb Acute Aggregate Risk 

HED has calculated the acute dietary risk for females 13-49 years of age in Section 5.2.1 

of this risk assessment. Since food is the only source contributing to the acute aggregate 

risk assessment, the acute aggregate risk assessment for mancozeb is equivalent to the 

acute dietary risk assessment detailed in Section 5.2.1. HED has no concern for acute 

aggregate risks to females 13 – 49 yrs, the subgroup of concern, resulting from exposure 

to mancozeb per se from the existing and new uses of mancozeb. 

7.1.2 ETU Acute Aggregate Risk 

HED has calculated the acute dietary risk for females 13 – 49 years of age from 

mancozeb-derived ETU in Section 5.2.1 of this risk assessment. Since HED considers 

only dietary (food and water) contributions to the ETU acute aggregate risk, the ETU 

acute aggregate risk assessment is equivalent to the ETU acute dietary (food and water) 

risk assessment for ETU detailed in Section 5.2.1. HED has no concern for acute 

aggregate risks to females 13 – 49 yrs, the subgroup of concern, resulting from exposure 

to mancozeb-derived ETU through food and water resulting from the existing and new 

uses of mancozeb. 

7.2 Short/Intermediate-Term Aggregate Risk

7.2.1 Mancozeb Short/Intermediate-Term Aggregate Risk Assessments 

7.2.1.1 Mancozeb Short/Intermediate-Term Home Garden Aggregate (Adult) 

Since there are no dermal endpoints selected for mancozeb, the home garden aggregate 

risk assessment does not include dermal exposure. Further, since residues of mancozeb 

are not expected in drinking water, only mancozeb food residues are considered. This 

assessment combines residential handler exposures (inhalation) to adult applicators plus 

average food exposures. The exposure value used for food represents the highest 

exposure found from all adult populations in the mancozeb chronic dietary exposure 

assessment. 

Aggregate short/intermediate-term home garden risk for adults far exceeds the level of 

concern of 1000 for this risk assessment and is not of concern. Mancozeb 

short/intermediate-term home garden aggregate (adult) risk calculations are summarized 

in the table below. 
Mancozeb Human Health Risk Assessment D327307 & D327318

Page 47 of 62 

Table 7.2.1.1 Mancozeb Short/Intermediate-Term Home Garden Aggregate (Adult) 

Risk Calculations 

Short/Intermediate-Term Scenario 

Population 

LOC for 

Aggregate 

Risk1

MOE 

food2

MOE 

oral3

MOE 

dermal4

MOE 

inhalation5

Aggregate MOE 

(food and 

residential)6

Adult 1000 130000 N/A N/A 890000 110000 

1

 The LOC is based on UFA = 10, UFH = 10, UFDB = 10 2

 MOE food = [(short/intermediate-term oral NOAEL)/(chronic dietary exposure)]. ST/IT oral NOAEL = 9.24 

 mg/kg/day; Chronic food exposure = 0.000071 mg/kg/day from Table 5.2.4.1 (highest exposed adult 

 subgroup) 

3

 N/A is “not applicable” since oral exposures are not expected for adult populations. 4

 N/A is “not applicable” since a dermal endpoint was not selected for mancozeb based on lack of systemic toxicity at 

 the high dose tested in the 28-day dermal study. 

5

 Inhalation MOE from Table 6.1.1 (backpack sprayer scenario) 

6

 Aggregate MOE (food and residential) = 1/ [(1/MOE food) + (1/MOE oral) + (1/MOE dermal) + (1/MOE inhalation)] 

7.2.1.2 Mancozeb Short-Term Treated Turf Aggregate (Toddler) 

Since there are no dermal endpoints selected for mancozeb and no likelihood of residues 

in drinking water, the mancozeb short-term treated turf aggregate risk assessment for 

toddlers combines residential incidental oral exposures with average food residues. The 

exposure value used for food represents the highest exposure found from all child 

populations in the mancozeb chronic dietary exposure assessment. 

HED calculated incidental oral exposures and risks to toddlers based on the assumption 

that the sod farm use labels would reflect a 3-day PHI. At that PHI, estimated risks to 

toddlers were below 1000 and were of concern. Because the individual incidental oral 

risks at a 3-day PHI were below the level of concern, no further aggregation could be 

conducted. 

HED calculated the PHI needed to bring the MOE for incidental oral risk to toddlers from 

exposure to mancozeb from treated turf above 1000. At a PHI of 5-days, assuming an 

additional 2 days for harvest, shipping and installation, MOEs for toddler incidental oral 

risk exceed 1000, and are no longer of concern. The aggregate risk assessment 

provided in this section assumes mancozeb exposures based on a PHI of 5-days for 

sod farm use of mancozeb. 

At a 5-day PHI for the sod farm use, mancozeb short-term aggregate risks for toddlers 

exposed to treated turf the aggregate risk is greater than 1000 and is not of concern. 

Mancozeb short-term treated turf aggregate risk calculations for toddlers are shown in the 

table below. 
Mancozeb Human Health Risk Assessment D327307 & D327318

Page 48 of 62 

Table 7.2.1.2 Mancozeb Short-Term Treated Turf Aggregate (Toddler) Aggregate Risk 

Calculations

Short-Term Scenario 

Population 

NOAEL 

mg/kg/day LOC1

Max 

Allowable 

Exposure2

mg/kg/day 

Average 

Food3 

mg/kg/day 

Residential 

Exposure4

mg/kg/day 

Aggregate MOE 

(food and 

residential)5

Toddler 9.24 1000 0.00924 0.000167 0.0086 1100 

1

 The LOC is based on UFA = 10, UFH = 10, UFDB = 10 2

 Maximum Allowable Exposure (mg/kg/day) = NOAEL/LOC 

3

 Average food residue is for most highly exposed child subpopulation from the chronic dietary assessment from Table 

 5.2.4.1 

4

 Residential Exposure = hand-to-mouth + object-to-mouth + soil ingestion exposure from Table 6.2.2.2. 

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

7.2.2 ETU Short-Term Risk Assessments 

7.2.2.1 ETU Short/Intermediate-Term Home Garden Aggregate 

The ETU short/intermediate-term home garden aggregate combines handler inhalation 

and dermal exposures and postapplication garden dermal exposures plus average food 

and water exposures for adults exposed to mancozeb-derived ETU. For youth exposed to 

mancozeb-derived ETU, the assessment combines postapplication garden dermal 

exposures with average food and water exposures. Average food and water exposure 

values reflect the most highly exposed adult or youth subpopulation from the chronic 

dietary assessment. 

The mancozeb-derived ETU short/intermediate-term home garden aggregate MOEs for 

adults and youth exceed 1000, the level of concern for this risk assessment and are not of 

concern. Aggregate risk calculations are shown in the table below. 
Mancozeb Human Health Risk Assessment D327307 & D327318

Page 49 of 62 

Table 7.2.2.1 ETU Short/Intermediate-Term Home Garden Aggregate Risk Calculations

Short/Intermediate-Term Scenario 

Population 

NOAEL 

mg/kg/day LOC1

Max 

Allowable 

Exposure2

mg/kg/day 

Average 

Food & 

Water 

Exposure3 

mg/kg/day 

Residential 

Exposure4

mg/kg/day 

Aggregate MOE 

(food and 

residential)5

Adults 5 1000 0.005 0.000030 0.000363 13000 

Youth 7 1000 0.007 0.000071 0.000240 22000 

1

 The LOC is based on UFA = 10, UFH = 10, UFDB = 10 2

 Maximum Allowable Exposure (mg/kg/day) = NOAEL/LOC 

3

 Average food and water exposure taken from most highly exposed adult or youth subpopulation from the chronic 

 dietary exposure assessment in Table 5.2.4.3. 4

 Residential Exposure = [Oral exposure + Dermal exposure + Inhalation Exposure]. Combined dermal and inhalation 

 exposure for adult handlers is 4.5 x 10-5 mg/kg/day (Table 6.1.2). Dermal post application exposure for 

 adults is 3.1 x 10-4 mg/kg/day (Table 6.2.1.1). Dermal postapplication exposure for youth is 2.4 x 10-4

 mg/kg/day (Table 6.2.1.1) 

5

 Aggregate MOE = [NOAEL /(Avg Food & Water Exposure + Residential Exposure)] 

7.2.2.2 ETU Short-Term Treated Turf Aggregate (Toddlers) 

The short-term treated turf aggregate risk assessment combines treated turf 

postapplication incidental oral and dermal exposures with average food and water 

exposures for toddlers. Average food and water exposure values reflect the most highly 

exposed child subpopulation from the chronic dietary assessment. Since incidental oral 

risks for toddlers from mancozeb-derived ETU were not of concern at a 3-day PHI, those 

values were used for this aggregate risk assessment. Increasing the PHI for the sod farm 

use to 5 days would result in less risk than shown below. 

The mancozeb-derived ETU short-term treated turf aggregate MOE for toddlers exceeds 

1000, the level of concern for this risk assessment and is not of concern. Aggregate risk 

calculations are shown in the table below. 
Mancozeb Human Health Risk Assessment D327307 & D327318

Page 50 of 62 

Table 7.2.2.2 ETU Short-Term Treated Turf (Toddlers) Aggregate Risk Calculations 

Short-Term Scenario 

Population 

NOAEL 

mg/kg/day LOC1

Max 

Allowable 

Exposure2

mg/kg/day 

Average 

Food & 

Water 

Exposure3 

mg/kg/day 

Residential 

Exposure4

mg/kg/day 

Aggregate MOE 

(food and 

residential)5

Toddlers 7 1000 0.007 0.000071 0.00596 1200 

1

 The LOC is based on UFA = 10, UFH = 10, UFDB = 10 2

 Maximum Allowable Exposure (mg/kg/day) = NOAEL/LOC 

3

 Average food and water exposure taken from most highly exposed child subpopulation from the chronic dietary 

 exposure assessment in Table 5.2.4.3. 

4

 Residential Exposure = incidental oral exposure + dermal exposure. Incidental oral exposure is 0.00376 mg/kg/day 

(Table 6.2.2.3). Dermal exposure is 0.0022 mg/kg/day (Table 6.2.2.4) 5

 Aggregate MOE = [NOAEL /(Avg Food & Water Exposure + Residential Exposure)] 

7.2.2.3 ETU Short/Intermediate-Term Treated Turf Aggregate (Adults “Golfers”) 

The short/intermediate-term treated turf aggregate risk assessment combines dermal 

exposures for adults participating in activities such as golf on treated turf exposed to 

mancozeb-derived ETU with chronic food and water exposures. 

The mancozeb-derived ETU short-term treated turf aggregate MOE for adults (“golfers”) 

exceeds 1000, the level of concern for this risk assessment, and is not of concern. 

Aggregate risk calculations are shown in the table below. 

Table 7.2.2.2 ETU Short/Intermediate-Term Treated Turf (Adults “Golfers”) 

Aggregate Risk Calculations 

Short-Term Scenario 

Population 

NOAEL 

mg/kg/day LOC1

Max 

Allowable 

Exposure2

mg/kg/day 

Average 

Food & 

Water 

Exposure3 

mg/kg/day 

Residential 

Exposure4

mg/kg/day 

Aggregate MOE 

(food and 

residential)5

Adults 

(Golfers) 5 1000 0.005 0.000030 0.00076 6300 

1

 The LOC is based on UFA = 10, UFH = 10, UFDB = 10 2

 Maximum Allowable Exposure (mg/kg/day) = NOAEL/LOC 

3

 Average food and water exposure taken from most highly exposed adult subpopulation from the chronic dietary 

 exposure assessment in Table 5.2.4.3. 

4

 Residential Exposure = Dermal exposure. Adult dermal exposure is 0.00076 mg/kg/day (Table 6.2.3.1) 5

 Aggregate MOE = [NOAEL/(Avg Food & Water Exposure + Residential Exposure)] 
Mancozeb Human Health Risk Assessment D327307 & D327318

Page 51 of 62 

7.3 Long-Term (Chronic) Aggregate Risk 

7.3.1 Mancozeb Chronic (Non-Cancer) 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 5.2.2 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. 

7.3.2 ETU Chronic (Non-Cancer) Aggregate Risk 

The long-term or chronic (non-cancer) aggregate risk for mancozeb-derived ETU 

includes contribution from dietary (food and water) exposure alone. The chronic (noncancer) aggregate risk assessment for mancozeb-derived ETU is equivalent to the 

mancozeb-derived ETU chronic dietary risk assessment conduction in Section 5.2.2 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 mancozebderived ETU from the existing and new uses of mancozeb. 

7.4 Cancer Aggregate Risk 

For the aggregate cancer risk assessment, HED combined residential handler and 

postapplication exposures for adults exposed to mancozeb-derived ETU from the home 

garden uses, as well as postapplication exposures to adults from contact with treated turf 

during activities such as golf. The combined residential exposure was then aggregated 

with dietary exposure to mancozeb-derived ETU from food and water and compared to 

the ETU Q1

*

. 

Because of the uncertainties regarding estimation of cancer potency and human exposure, 

risk estimates ranging from 1 x10-6 to 3 x10-6 are generally considered 

indistinguishable. Additionally, HED generally has no concern for cancer risk estimates 

which do not exceed 3 x10-6. Mancozeb-derived ETU aggregate cancer risk for the U.S 

Population does not exceed 3 x 10-6 and is; therefore not of concern. ETU aggregate 

cancer calculations are shown in table 7.5, below. 
Mancozeb Human Health Risk Assessment D327307 & D327318

Page 52 of 62 

Table 7.5 ETU Aggregate Cancer Calculations 

Population 

Q1* 

(mg/kg/day)-1

Negligible Risk 

Level1 

Chronic Food 

& Water 

Exposure2

(mg/kg/day) 

Residential 

Exposure 3

(LADD)

Aggregate 

Cancer Risk 

(food, water 

and 

residential)4

U.S. Pop 6.01 x 10-2 3 x10-6 3.2 x10-5 3.98 x 10-6 2.2 x 10-6 

1 Because of the uncertainties regarding estimation of cancer potency and human exposure, risk estimates ranging from 

 1 x10-6 to 3 x10-6 are generally considered indistinguishable. Additionally, HED generally has no concern for 

 cancer risk estimates which do not exceed 3 x10-6 

2 From Table 5.2.4.3 

3

 Handler LADD (low pressure handwand – highest exposure scenario) is 3.8 x10-7 from Table 6.1.3. Home garden 

 postapplication LADD is 2.6 x10-6 from Table 6.2.1.2 (risk/ Q1* = exposure). Treated turf post app LADD 

 is 1.0 x10-6 from Table 6.2.3.2. Total residential exposure is 3.98 x10-6. 4

 Aggregate Cancer Risk is (total LADD plus chronic food exposure) x Q1* 

7.5 ETU Aggregate Exposure from All Sources 

 D337241, 42005, T. Goodlow

ETU aggregate exposure and risk assessments were conducted to support the new 

mancozeb uses that are the subject of this action, as well as to support new use of the 

EBDC, metiram. The acute, chronic and cancer aggregate assessments for ETU 

considered food, water and residential exposures resulting from current and proposed 

uses of metiram, mancozeb and maneb; only mancozeb and maneb are used in residential 

settings. Acute and chronic risks from all sources of ETU were not of concern; however, 

the ETU aggregate cancer risk exceeds HED’s level of concern (3.8 x 10-6). HED 

conducted sensitivity analyses and determined the greatest contributors to ETU exposure 

are bananas, leaf lettuce, water, turnip greens, grape juice and mangoes. If the proposed 

metiram import tolerance in/on bananas (from metiram applications) is removed from the 

aggregate assessment, then the aggregate cancer risk does not exceed HED’s level of 

concern (3.2 x 10-6). All other sensitivity analyses result in aggregate risks exceeding the 

level of concern. Note that the metiram-derived ETU residue values from crop field trials 

used in the aggregate assessment are considered to be overestimates. Projected percent 

crop treated information was not available, so percent imported information was used 

(virtually 100%) and it is highly unlikely that all bananas will be treated. In general, 

monitoring data available for other commodities show much lower residues than field 

trial data, so the actual exposure is likely to be lower. For these reasons, HED is 

requiring the submission of monitoring data for metiram and ETU on bananas. 

8.0 Cumulative Risk Characterization/Assessment 

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 
Mancozeb Human Health Risk Assessment D327307 & D327318

Page 53 of 62 

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 Pathway 

D317368, 5/31/2005, T. Dole 

9.1 Occupational Handler Exposures and Risks

Handler Exposure Scenarios 

Based upon the label instructions for the proposed new uses of Dithane M-35 it is 

assumed that aerial and airblast applications would be made to almonds and that aerial, 

chemigation and groundboom applications would be made to the vegetable crops 

(broccoli, cabbage, lettuce and peppers). Although Dithane M-35 is a wettable powder 

(WP) formulation, scenarios for Dithane DF, which is a dry flowable formulation (DF) 

are also considered because the existing residue chemistry data support use of the DF 

formulation and because the DF formulation is less hazardous to handle. Although 

flagger scenarios are normally considered for aerial application, they are not considered 

for mancozeb because the RED prohibits the use of human flaggers. 

Calculation Methods 

The proposed new uses of mancozeb are similar to the existing uses that were included in 

the Mancozeb ORE Assessment for the RED (D317368, T. Dole, 5/31/2005) and the 

same calculation methods were used. Only inhalation MOEs were calculated for 

mancozeb exposures because no effects were observed in the mancozeb 28-day dermal 

toxicity study. In the case of ETU, however, both inhalation and dermal exposures were 

considered for both noncancer and cancer risk assessments. The level of concern (LOC) 

for both the mancozeb and ETU occupational risk assessments is for MOEs below 100. 

The level of concern for occupational cancer risks is 1 x 10-4 to 1 x 10-6 as discussed in 

the Dan Barolo memo of August 14, 1996. According to this memo “In considering 

applications for new registrations with non-dietary cancer risks, OPP carefully examines 

those uses with potential risks in the 10-6 to 10-4 range to seek ways of reducing those 

risks before registration occurs”. 

Assumptions Used for Calculating Occupational Handler Risks 

The following assumptions and exposure factors were used: 

• A body weight of 70 kg was used for assessing mancozeb inhalation non-cancer risks 

and ETU cancer risks because the endpoints were not gender specific. 
Mancozeb Human Health Risk Assessment D327307 & D327318

Page 54 of 62 

• A body weight of 60 kg was used for assessing ETU non-cancer risks because the 

ETU endpoint is specific to females. 

• The amount of mancozeb that converts to ETU is 0.1 percent during mixing and 0.2 

percent during loading based upon 1989 Tank Mix Data as discussed in the 

Mancozeb ORE Assessment for the RED. 

• The dermal absorption factors are 1.0 percent for mancozeb and 26 percent for ETU. 

• The maximum proposed application rates were used. 

• The daily acres treated per day are from the Health Effects Division Science 

Advisory Committee on Exposure Policy 9: Standard Values for Daily Acres 

Treated in Agriculture which was completed on July 5, 2000. The following values 

were used: 

 - Aerial Application: 350 acres per day for almonds 

- Chemigation: 350 acres per day for vegetables; 

- Groundboom: 80 acres per day treated for vegetables; 

- Airblast: 40 acres per day for almonds; 

• The cancer risks were assessed using thirty days per year as was done in Mancozeb 

ORE Assessment for the RED for the existing uses. 

• Flagging exposures were not assessed because the Mancozeb RED prohibits human 

flagging. This is consistent with the fact that Global Positioning Satellite technology 

is now predominantly used as indicated by the 2003 National Agricultural Aviation 

Association (NAAA) survey. 

• Baseline PPE includes typical work clothing (i.e., a long-sleeved shirt, long pants, 

shoes, socks, and no respiratory protection). It does not include chemical-resistant 

gloves 

. 

• Single Layer PPE includes chemical-resistant gloves in addition to baseline clothing. 

• PF5 Respirator: is a respirator with a protection factor of 5 (i.e., it provides 80 

percent inhalation protection). A PF5 respirator is a filtering facepiece respirator 

(i.e. a dust mask) that provides dust/mist filtering only. 

• It was assumed that that aerial application would be done using closed cockpit 

aircraft as required by the RED. 

• It was assumed that groundboom and airblast application would be done using open 

cab tractors because closed cab tractors are not required by the RED. 
Mancozeb Human Health Risk Assessment D327307 & D327318

Page 55 of 62 

Unit Exposure Data Sources 

All of the unit exposure values used in this assessment are from the PHED Surrogate 

Guide of August 1998. This guide is a series of tables of standard unit exposure values 

for many occupational scenarios that can be utilized to ensure consistency in exposure 

assessments. 

Occupational Handler Risk Summary 

 The handler risks for the mixing and loading of mancozeb for the new use crops are 

shown in Table 9.1.1. The mancozeb inhalation MOEs for mixing/loading WP without 

respirators are below the level of concern of 100. If PF5 respirators are added, the 

inhalation MOEs range from 100 to 300 which exceed the level of concern. If the DF 

formulation is used, however, the inhalation MOEs range from 1100 to 3400 without 

respirators. The ETU MOEs for mixing loading WP are also less than the ETU MOEs 

for mixing/loading DF. The cancer risks for mixing/loading WP are in 10-4 range if 

respirators are not worn, however, they are in the 10-5 range if PF5 respirators are worn. 

The cancer risks for mixing/loading DF are in 10-6 range, however, even if respirators are 

not worn. 

Table 9.1.1: Occupational Handler Risks for Mixing/Loading Mancozeb for the Proposed New Uses

Crops Treated lb ai per 

acre 

 acres per 

day

 Mancozeb 

Inhalation 

MOE without 

Respirator

Mancozeb 

Inhalation 

MOE with 

PF52

Respirator 

ETU MOE 

with Single 

Layer PPE3

ETU MOE with 

Single Layer 

PPE and PF5 

Respirator 

ETU Cancer 

Risk with 

Single Layer 

PPE

ETU Cancer 

Risk with 

Single Layer 

PPE and PF5 

Respirator

Mixing Loading WP (Dithane M-45) 

almonds 

peppers (east) 

other vegetables1

4.8 

2.4 

1.6 

350 

350 

350 

20 

41 

61

100 

200 

300

52 

100 

160 

220 

430 

650 

2 x 10-4 

1 x 10-4 

7 x 10-5 

5 x 10-5 

2 x 10-5 

2 x 10-5 

Mixing/Loading DF (Dithane DF-45) 

almonds 

peppers (east) 

other vegetables1

4.8 

2.4 

1.6 

350 

350 

350 

1,100 

2,300 

3,400

not 

needed 

1,400 

2,900 

4,300 

not needed 

7 x 10-6 

4 x 10-6 

3 x 10-6 

not needed 

1. Includes broccoli, cabbage, lettuce and peppers 

2. A PF5 respirator is a filtering facepiece respirator (i.e. a dustmask) that reduces inhalation exposure by a factor of 5. 

3. Single layer PPE includes standard work clothing (i.e. long pants, long sleeve shirts) and chemical resistant gloves. 

*MOES in bold font do not exceed the target MOE of 100 for mancozeb or ETU and are of concern.

The risks of mixing/loading WP were recognized in the Mancozeb RED and the 

following mitigation was adopted: "To mitigate handler risks from this use, the WP 

labels must require the following personal protective equipment PPE: single layer with 

gloves and a PF 5 dust-mist respirator. The Agency believes that these measures will 

mitigate handler risk concerns to the extent feasible. Cancer risk estimates for handlers 

wearing single layer PPE, gloves and a PF 5 respirator are in the range of 1 x 10-6 for 

groundboom, airblast, and hand application (e.g. handwand). For aerial application and 

chemigation, cancer risks are in the 10-5 range and the chronic MOE for small grains, 

cotton, and cucurbits is 89 with the PPE described above. EPA believes that the respirator 

requirement for the WP formulation will have a positive effect in reducing potential 

exposures, resulting in a gradual shift in the industry to the safer DF formulation." 
Mancozeb Human Health Risk Assessment D327307 & D327318

Page 56 of 62 

The handler risks for the application of mancozeb to the new use crops are shown in 

Table 9.1.2, below. The mancozeb and ETU MOEs exceed 100 with baseline PPE and 

are not of concern. The cancer risks are in the 10-6 range and are also not of concern. 

Table 9.1.2: Occupational Handler Risks for Applying Mancozeb for the Proposed New Uses

Crops Treated lb ai per 

acre 

 acres per 

day

 Mancozeb 

Inhalation 

MOE without 

Respirator

Mancozeb 

Inhalation 

MOE with 

PF52

Respirator 

ETU MOE 

with Baseline 

PPE3

ETU MOE with 

Single Layer 

PPE 

ETU Cancer 

Risk with 

Baseline 

 PPE

ETU Cancer 

Risk with 

Single Layer 

PPE

Aerial Application (Closed Cockpit Aircraft) 

almonds 

peppers (east) 

other vegetables1

4.8 

2.4 

1.6 

350 

350 

350 

13,000 

39,000 

26,000

Not 

needed 

15,000 

31,000 

46,000 

Not 

 needed 

7 x 10-7 

3 x 10-7 

2 x 10-7 

Not 

needed 

Groundboom Application (Open Cab Tractors) 

peppers (east) 

other vegetables1 2.4 

1.6 

350 

350 

10,000 

16,000

Not 

needed 

21,000 

63,000 

Not 

needed 

5 x 10-7 

3 x 10-7 

Not 

needed 

Airblast Application (Open Cab Tractors) 

almonds 4.8 40 1,700 Not needed 1,900 Not needed 5 x 10-6 4 x 10-6 

1. Includes broccoli, cabbage, lettuce and peppers 

2. Baseline PPE includes standard work clothing (i.e. long pants and long sleeve shirts). 

3. Single layer PPE includes standard work clothing and chemical resistant gloves. 

*MOES in bold font do not exceed the target MOE of 100 for mancozeb or ETU and are of concern.

 

9.2 Occupational Postapplication Exposures and Risks

Exposure Scenarios 

The mancozeb new uses include the following crop groups: 

• Trees, Nut, (Almond) 

• Vegetable, Brassica (Broccoli and Cabbage) 

• Vegetable, fruiting (Pepper) 

• Vegetable, leafy (Lettuce); 

Within each agronomic group, a variety of cultural practices are required to maintain the 

included crops. These practices are varied and typically involve light contact with 

immature plants as well as heavy contact with more mature plants. The exposures 

scenarios and transfer coefficients for the new use crops are listed in Table 9.2.1, below: 

Table 9.2.1 - Post Application Exposure Scenarios and Transfer Coefficients

Crop Group (Specific Crops) Post Application Exposure Scenarios Transfer 

Coefficient 

(cm2

/hr) 

Tree, Nut (Almonds) Low - Irrigation, scouting, thinning, weeding 

Medium – N/A 

High – Pruning (Not assessed, done in winter)

400 

N/A 

N/A

Vegetable, Brassica Low - Irrigation, scouting, thinning weeding immature plants 

Medium - Irrigation and scouting mature plants 

2000 

4000 
Mancozeb Human Health Risk Assessment D327307 & D327318

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Table 9.2.1 - Post Application Exposure Scenarios and Transfer Coefficients

Crop Group (Specific Crops) Post Application Exposure Scenarios Transfer 

Coefficient 

(cm2

/hr) 

(Broccoli and Cabbage) High - Hand harvesting, pruning, topping, tying mature plants 5000 

Vegetable, fruiting (Pepper) Low - Irrigation, scouting, thinning, weeding immature plants 

Medium - Irrigation and scouting mature plants 

High - Hand harvesting, pruning, staking, tying 

500 

700 

1000 

Vegetable, leafy (Lettuce) Low - Irrigation, scouting, thinning weeding immature plants 

Medium - Irrigation and scouting mature plants 

High - Hand harvesting, pruning, and thinning mature plants 

500 

1500 

2500 

Data Used for Occupational Postapplication Exposure Scenarios 

Eight dislodgeable foliar residue (DFR) studies were submitted in support of the 

reregistration of mancozeb and these were reviewed in Mancozeb ORE Assessment for 

the RED. The DFR studies were conducted on apples, grapes and tomatoes using 

airblast and groundboom application of Dithane DF dry flowable fungicide. The DFR 

studies were extrapolated to the new use crops as shown in Table 1 below by considering 

the effects of application method, crop morphology and climate. Where two or more 

studies were available for the same crop type and climate the study with the best data 

quality was selected to represent that scenario. Typically the more recent studies had 

better data quality because the field fortification levels were usually more representative 

of the measured DFR levels, the field recovery was less variable and the limits of 

quantification were lower. In the case of Florida field tomatoes, however, an older study 

was used because a substantial rain event (7.4 inches) occurred on DAT 3 of the more 

recent study. 

 

Table 9.2.2 - Assignment of Mancozeb DFR Study Data to the New Use Crops

Crop Group 

(Labeled Crops) 

Region Study Used (MRID) Parameters Matched 

Trees, Nut, (Almond) West WA Airblast Apple (449596-02) application method, climate 

Vegetable, Brassica 

(Broccoli and Cabbage)

East 

West Florida Groundboom Tomato (425602-01) 

California Groundboom Tomato (449596-02) 

application method, climate 

application method, climate 

Vegetable, fruiting (Pepper) East 

West 

Florida Groundboom Tomato (425602-01) 

California Groundboom Tomato (449596-02) 

crop, application method, climate 

crop, application method, climate 

Vegetable, leafy (Lettuce) East 

West 

Florida Groundboom Tomato (425602-01) 

California Groundboom Tomato (449596-02) 

crop, application method, climate 

crop, application method, climate 

Exposure Assumptions, factors and Transfer Coefficients 

A series of assumptions, factors and transfer coefficients served as the basis for 

completing the occupational postapplication worker risk assessments. Each assumption 

and factor is detailed below. 

• The body weights, dermal absorption factors and toxicological endpoints are the 

same as those used for the occupational handler assessments. 
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• Only maximum application rates were used for the postapplication assessments 

• All postapplication cancer risk were been assessed using 30 days per year.

• Risks were calculated using the transfer coefficients that are listed in Table 1. These 

transfer coefficients were generally taken from HED’s revised policy entitled Policy 

003.1 Science Advisory Council For Exposure Policy Regarding Agricultural 

Transfer Coefficients (August 7, 2000) and are subject to further revision as more 

data becomes available. 

Calculation Methods 

Because a dermal endpoint was not selected for mancozeb, post application exposures 

were assessed only for ETU and the specific calculation methods are detailed in the ORE 

Assessment for the RED. The level of concern for the ETU postapplication occupational 

risk assessment is for MOEs below 100. The ETU exposure was calculated by adding the 

ETU dose absorbed from the leaf surface to the ETU that is metabolically converted from 

absorbed mancozeb.

Occupational Postapplication Risk Estimates 

The occupational postapplication risks are summarized in Table 9.2.3. Current label 

requirements specify a 24 hour Restricted Entry Interval (REI). The non-cancer risks are 

not of concern at the current REI with MOEs that exceed the level of concern of 100. The 

cancer risks are also less than 1x10-4 for all of the scenarios and are not of concern. 

Table 9.2.3 - ETU from Mancozeb Occupational Post Application Risks

Short/Intermediate Term MOE on Day 1 

Crop Group 

Application 

Rate 

(lb a.i./acre) 

Low 

Exposure 

Scenarios* 

Medium 

Exposure 

Scenarios* 

High 

Exposure 

Scenarios* 

ETU from Mancozeb Non-Cancer Risks (i.e. MOEs) 

Almonds 4.8 3600 N/A N/A 

Brassica (Broccoli and Cabbage) - West 

Brassica (Broccoli and Cabbage) - East 

1.6 

1.6 

2900 

2300 

1500 

1100 

1200 

920 

Leafy Vegetables (Lettuce) - West 

Leafy Vegetables (Lettuce) - East 

1.6 

2.4 

12000 

9200 

3900 

3100 

2400 

1800 

Vegetable, fruiting (Pepper ) - West 

Vegetable, fruiting (Pepper) - East 

1.6 

2.4 

10000 

7200 

7200 

5200 

5000 

3600 

ETU from Mancozeb Cancer Risks 

Almonds 4.8 3 x 10-6 N/A N/A 

Brassica (Broccoli and Cabbage) - West 

Brassica (Broccoli and Cabbage) - East 

1.6 

1.6 

4 x 10-6 

5 x 10-6 

7 x 10-6 

1 x 10-5 

9 x 10-6 

1 x 10-5 

Leafy Vegetables (Lettuce) - West 

Leafy Vegetables (Lettuce) - East 

1.6 

2.4 

9 x 10-7 

1 x 10-6 

3 x 10-6 

4 x 10-6 

5 x 10-6 

6 x 10-6 

Vegetable, fruiting (Pepper ) - West 

Vegetable, fruiting (Pepper) - East 

1.6 

2.4 

9 x 10-7 

1 x 10-6 

1 x 10-6 

2 x 10-6 

2 x 10-6 

3 x 10-6 

*Task descriptions for each crop and exposure scenario are included in Table 9.2.1. 
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10.0 Data Needs and Label Recommendations 

10.1 Toxicology 

The following toxicology data gaps have been identified either in previous risk 

assessments or in this assessment. 10X database uncertainty factors for mancozeb and 

ETU were applied to account for missing data. Because thyroid toxicity seen with 

mancozeb is due to ETU, a comparative thyroid toxicity study is required for ETU only. 

Mancozeb 

• An acute neurotoxicity study 

• A developmental neurotoxicity study 

ETU 

• A developmental toxicity study in rabbits 

• A 2-generation reproduction study in rats 

• A comparative thyroid study in adults and offspring 

• A developmental neurotoxicity study 

10.2 Residue Chemistry 

The following residue chemistry data needs have been identified specific to this new use 

action and are required to support the requested new uses. 

• One leaf lettuce trial employed use of a “U-boom” application device (which 

applies the material to the undersides of the plant as well as over the top), 

resulting in considerably higher residues than the remaining trials. The proposed 

label must be amended to specifically prohibit use of such a device. Alternatively 

the petitioner should submit a full set of trials reflecting this application 

technique. 

• The proposed use for almonds must be amended to remove the instruction to add 

a surfactant to the spray mixture unless the petitioner provides confirmation that a 

surfactant was used in the spray mixtures at the crop field trials used to establish 

the almond tolerance. 

• The petitioner should provide amended Section Fs to express the tolerances as 

carbon disulfide, and change the proposed levels to broccoli, 7 ppm; cabbage, 9 

ppm; head lettuce, 3.5 ppm; leaf lettuce, 18 ppm; pepper, 12 ppm: almond hulls, 4 

ppm. 

The following data were required in the RED and remain outstanding. 

• Ruminant feeding study 

• Analytical method for ruminant commodities 

• Confined rotational crop study 
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• Various crop field trial data to support existing uses 

10.3 Occupational and Residential Exposure 

No additional data are required with respect to occupational or residential exposure and 

risk.

11.0 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 LowIncome 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 United States Department of Agriculture 

(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 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. 

12.0 Regulatory Recommendations 

Provided the existing label for the sod farm turf use of mancozeb is revised to stipulate an 

5-day PHI, there is nothing in this mancozeb specific risk assessment to preclude the 

establishment of the requested tolerances at the levels stipulated below. 

Further, HED notes that the new uses that are the subject of this action have been 

included in the forthcoming ETU aggregate risk assessment. The ETU aggregate 

assessment considers exposure and risk from ETU derived from all existing and pending 

uses of the EBDC pesticides. The addition of these new mancozeb uses does not result in 

aggregate ETU exposures or risks of concern when considered with the existing and 

pending uses of EBDC pesticides. 
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Provided the residue chemistry data needs specific to these new uses listed in Section 

10.2 of this risk assessment are addressed, HED recommends in favor of the 

establishment of tolerances at the levels noted in Table 12.l, below. 

Table 12.1 New Tolerance Summary for Mancozeb 

Crop Commodity 

Proposed 

Tolerance 

(ppm) 

Recommended 

Tolerance 

(ppm) 

Comments 

(Correct commodity definition) 

Tolerances needed under §180.176 (a) 

Broccoli 13 7.0 Broccoli 

Cabbage 10 9.0 Cabbage 

Lettuce 10 3.5 Lettuce, head 

18 Lettuce, leaf 

Peppers 7 12 Pepper 

Almond nuts 0.1 0.1 Almond 

Almond Hulls 10 4.0 Almond, hulls 

References:

Mancozeb. Heath Effects Division (HED) Human Health Risk Assessment to Support 

Reregistration. 

D317371, K. Farwell, 6/3/05 

Mancozeb Toxicity Endpoints for Risk Assessment 

D317369, K. Farwell, 6/3/2005 

Mancozeb: Residue Chemistry Chapter of the Reregistration Eligibility Decision 

D305815, C. Olinger, 6/14/05 

Review of Mancozeb Incident Reports 

D286184, J. Blondell, 10/16/02 

Mancozeb on Broccoli, Cabbage, Lettuce, and Peppers. Summary of Analytical 

Chemistry and Residue Data. PP# 4F4333. 

D294203, C. Olinger, 4/3/07 

Mancozeb on Almonds. Summary of Analytical Chemistry and Residue Data. 

PP#4F4324. 

D289183, C. Olinger, 4/5/07 

Revision No. 2: Estimated Drinking Water Concentration of Ethylenebisdithiocarbamate 

(EBDC) Degrated Ethylenethiourea (ETU) for the Use in Human Health Risk 

Assessment 

D290057, R. Parker, 8/26/2004 
Mancozeb Human Health Risk Assessment D327307 & D327318

Page 62 of 62 

Estimated Drinking Water Concentrations of ETU (Ethylene-thio-urea, degradate of 

mancozeb, and common degradate of EBDCs “Ethene-bis-dithio-carbamates”) for Use in 

Human Health Risk Assessment. 

D323143 and D323141, M. Ruhman, 8/11/2006 

PP#4F4324 and 4F4333 Mancozeb Acute, Chronic, and Cancer Dietary Exposure 

Assessments for New Tolerances on Almonds, Broccoli, Cabbage, Lettuce, and Peppers. 

D323878 and D323879, C. Olinger, 4/17/07 

Mancozeb: 2nd Revised Occupational and Residential Expsoure Assessment and 

Recommendations for the Reregistration Eligibility Decision Document 

D317368, T. Dole, 5/31/2005 

Reregistration Eligibility Decision for Mancozeb 

D. Edwards, 9/20/05 

Ethylenethiourea (ETU) from EBDCs: Health Effects Division (HED) Human Health 

Risk Assessment of the Common Metabolite/Degradate ETU 

D33724, T. Goodlow, 2007