UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

Date: June 20, 2014 

Subject: Hydrazine. Occupational and Residential Exposure Cancer Screen for existing 

uses of Maleic Hydrazide/Hydrazine on Turf, Tobacco, Potatoes, Ornamental 

shrubs and trees, and for control of Onions and Garlic in dormant turf. 

PC Code: 05150 I /Maleic Hydrazide 

Decision No.: 481781 

Petition No.: NA 

Risk Assessment Type: Occupational/Residential Cancer 

Exposure Assessment 

TXRNo.:NA 

DP Barcode: 420405 

Registration No.: NA 

Regulatory Action: Registration 

Review 

Case No.: 0381 

CASNo.: 123-33-1 

From: James S Miller 

175 MRIDNo.:NA 

Envirorunental Scient'' 

Risk Assessment Branch 4 

Health Effects Division (7509P) 

Through: . Susan Hummel -'U - Branch Senior Scientist £~7k: 

To: 

Risk Assessment Branch 4 

Health Effects Division (7509P) 

and 

Kelly ORourke, Biologist /L))J.., 1- 1 1 

· [)\?:S, .. vz/l. 

Jeff Evans, Senior Scientist J 

Exposure Science Advisory Committee (ExpoSAC) I HED 

Ricardo Jones, Chemical Review Manager 

Tom Moriarty, Teain Leader 

RMIB 1, Pesticide Re-Evaluation Division (7 508P) 

Page I of 17 
Table of Contents 

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

2.0 Hazard Characterization ....................................................................................................... 4 

3.0 Use Profile ........................................................................................................................... 4 

4.0 Residential Exposure and Cancer Risk Estimates ............................................................... 6 

4.1 Residential Handler Exposure and Cancer Risk Estimates .............................................. 6 

5.2 Residential Post-application Exposure/Risk Estimates .................................................... 8 

5.3 Combined Residential Risk Estimates (Multiple Exposure Scenarios) ........................... 9 

5.4 Spray Drift .. .................................................................................................................... 11 

6.0 Occupational Exposure and Cancer Risk Estimates .......................................................... 11 

6.1 Occupational Handler Exposure Cancer Risk Estimates ............................................... 11 

6.2 Occupational Post-application Exposure and Cancer Risk Estimates .. ............ .... ......... 13 

6.2.1 Occupational Post-application Inhalation Exposure and Cancer Risk Estimates ... 13 

6.2.2 Occupational Post-application Dermal Exposure and Cancer Risk Estimates ....... 14 

Appendix A. Summary of Occupational and Residential Non-cancer Algorithms ..................... 16 

Appendix B. Summary of Occupational and Residential Cancer Algorithms ............................. ~ 

Page 2 of 17 
Page 3 of 17

1.0 Executive Summary

Although toxicological endpoints of concern have not been identified for the maleic hydrazide

human health assessment, an occupational and residential exposure assessment was conducted 

for the impurity, hydrazine. The impurity hydrazine is a carcinogen, with a Q1* of 3.0 

(mg/kg/day)-1. The limit of 15 ppm for hydrazine in maleic hydrazide technical products is still 

effective as was set in 1982, at the conclusion of the Rebuttable Presumption Against 

Registration (RPAR), (EPA, 1982). Therefore, for purposes of Registration Review, a highly 

conservative residential and occupational cancer exposure screen was performed to re-evaluate 

the safety of the 15 ppm hydrazine limit. 

Maleic hydrazide potassium salt (parent compound), and consequently its impurity hydrazine, is

used both in occupational and residential settings. It is used as a plant growth regulator to control 

sucker growth on tobacco, to inhibit sprout growth in stored onions and potatoes, to retard the 

growth of turf and to control sprouts on nonbearing apple and citrus trees, forest trees, and 

ornamental plants. It is also used as an herbicide to control quick grass, wild onions, wild garlic 

and other undesirable weeds in terrestrial nonfood crops, on fallow land, industrial areas and 

along roadsides and other rights-of-way. Application equipment includes groundboom, backpack

and mechanically pressurized handgun sprayers, and fixed wing aircraft. Residential uses 

include applications to control wild garlic and wild onions in dormant turfgrass as well as spot 

treatments against fence, trellis and other hard to mow areas. It is applied by backpack, hose-end, 

and pressurized handgun sprayers. 

Occupational and residential application rates were calculated using the maximum application 

rate per specific use of maleic hydrazide (parent) multiplied by 0.0015% to adjust for the ratio of 

parent (assuming 100%) to hydrazine. Specific rates are included in the occupational and 

residential sections that follow.

Personal protective equipment (PPE) required on the labels include long-sleeved shirt, long 

pants, chemical resistant gloves, shoes and socks. Labels also note the restricted entry interval 

(REI) is 12 - 48 hours where applicable. All calculations were conducted using a body weight of 

80 kg, and a Q* of 3.00 (mg/kg-day)-1.

Human Studies Review

This risk assessment relies in part on data from studies in which adult human subjects were 

intentionally exposed to a pesticide or other chemical. These data, which include studies from 

PHED 1.1; the AHETF database; the Outdoor Residential Exposure Task Force (ORETF) 

database; the ARTF database; the Residential SOPs; are (1) subject to ethics review pursuant 

to 40 CFR 26, (2) have received that review, and (3) are compliant with applicable ethics 

requirements. For certain studies, the ethics review may have included review by the Human 

Studies Review Board. Descriptions of data sources, as well as guidance on their use, can be 

found at the Agency website1. 

 

1 http://www.epa.gov/pesticides/science/handler-exposure-data.html and 

http://www.epa.gov/pesticides/science/post-app-exposure-data.html
Page 4 of 17

2.0 Hazard Characterization

The toxicological database for maleic hydrazide is complete and sufficient to characterize 

potential hazards and to support Registration Review. While exposure to maleic hydrazide is 

possible via residential and occupational use patterns, HED has not identified any toxicological 

endpoints for a human health risk assessment. Therefore, HED concludes that there is no risk and 

no quantitative residential, aggregate or occupational risk assessments are needed; a qualitative 

risk assessment is more appropriate.

The US EPA National Center for Environmental Assessment (NCEA) has classified hydrazine as 

a Group B2, probable human carcinogen (USEPA, 1999). For the HED cancer residential and 

occupational exposure screen, the oral cancer slope factor is most relevant. NCEA relied on a 

hydrazine sulfate (in water) gavage study in mice for the dose-response data for the oral cancer 

slope factor. Liver hepatomas were observed in CBA/cb/Se male mice (Biancifiori, 1970). The 

oral cancer slope factor for hydrazine is 3.0 (mg/kg/day)-1using the linearized multistage 

procedure. The carcinogenicity of hydrazine is discussed in EPA’s Integrated Risk Information 

System (IRIS, 2002). For a detailed discussion of confidence in the potency estimates, please 

refer to the IRIS website. There are no other known toxic endpoints identified for hydrazine; 

therefore, a non-cancer assessment was not conducted.

3.0 Use Profile 

Table 3.1. Summary of Directions for Use of Maleic Hydrazide and impurity: Hydrazine.

Application,

Timing, Type, 

and Equip.

Formulation 

[EPA Reg. 

No.]1

Applic. Rate

(lb a.i./A)1

Max. No. 

Applic. 

/Season

Max. 

Seasonal 

Applic. Rate

(lb a.i./A)

or

(lbs a.i. / gal)

PHI 

(days)

Use Directions and 

Limitations

Use Site 1

Tobacco: 

1 app/yr.

Groundboom, 

Aerial, 

Manually 

Pressurized 

Handgun

WDG:

EPA Reg. No. 

400-165

0.00014

(registrant 

provided)

1 0.00014 7

Applications are to be applied 

to the upper 1/3 to 1⁄2 of the 

plant, therefore, do not use 

drop nozzles: no under spray is 

desired. 1 application is desired 

unless rains occur within 6 

hours after initial application is 

made. 12 - 48 hr. REI

Use Site 2
Page 5 of 17

Table 3.1. Summary of Directions for Use of Maleic Hydrazide and impurity: Hydrazine.

Application,

Timing, Type, 

and Equip.

Formulation 

[EPA Reg. 

No.]1

Applic. Rate

(lb a.i./A)1

Max. No. 

Applic. 

/Season

Max. 

Seasonal 

Applic. Rate

(lb a.i./A)

or

(lbs a.i. / gal)

PHI 

(days)

Use Directions and 

Limitations

Potatoes:

1 app/yr.

Apply 2 to 3 

weeks past full 

bloom.

Groundboom, 

Aerial

WDG:

EPA Reg. No. 

400-165

0.00006 1 0.00006 N/A

Applications should be made 

when the smallest tubers that 

are harvested are 2 to 3 inches 

in diameter or about 2 to 2.5 

ounces in weight. 12 hr. REI

Use Site 3

Onions/ 

Garlic:

Groundboom, 

Aerial

WDG:

EPA Reg. No. 

400-165

0.000039 1 0.000039 10 - 14

Applications should be made 

when the bulbs are fully 

mature, have at least 5 to 8 

green leaves, and necks soft 

enough for the tops to fall. 12 

hr. REI

Use Site 4

Turf:

Groundboom, 

Manually 

Pressurized 

Handgun

Sprayer

WDG:

EPA Reg. No. 

400-165

Commercial

0.00012

1

(Spring or 

Fall) 

0.00012 N/A

Applications are mostly used as 

a substitute for mechanical 

mowing on commercial turf 

locations such as hard to mow 

areas along highways, airports 

property, military installations, 

Federal , state, municipal 

properties, golf course roughs 

and residential (band/edge) and 

spot treatment areas. 

12 hr. REI

Manually 

Pressurized 

handwand, 

Backpack, and 

hose-end 

sprayers

WDG:

EPA Reg. No. 

400-165

Residential

0.000010

(lbs ai/gal)

(registrant 

provided)

2

0.000020

(lbs ai/gal) N/A

Use Site 5

Ornamental 

Shrubs and 

Trees:

Manually 

Pressurized 

Handgun, 

Backpack 

sprayer

WDG:

EPA Reg. No. 

400-165

0.0000006 

(lbs ai/gal) 1

0.0000006

(lbs a.i. / gal)

NA

Apply to plants that have 

recently been pruned. Apply 

once a year

Use Site 6
Page 6 of 17

Table 3.1. Summary of Directions for Use of Maleic Hydrazide and impurity: Hydrazine.

Application,

Timing, Type, 

and Equip.

Formulation 

[EPA Reg. 

No.]1

Applic. Rate

(lb a.i./A)1

Max. No. 

Applic. 

/Season

Max. 

Seasonal 

Applic. Rate

(lb a.i./A)

or

(lbs a.i. / gal)

PHI 

(days)

Use Directions and 

Limitations

Fallow Land:

Groundboom,

Aerial,

Manually 

Pressurized 

Handgun

WDG:

EPA Reg. No. 

400-165

0.00018 1 0.00018 NA

Apply after crop harvest

Not approved in Arizona and 

California

1 Application rates taken from label: Royal MH-30 SG: EPA Reg No. 400-165; except for tobacco and turf, for which Registrant provided 

information regarding higher use rates . Application rate calculated: max application rate (parent, maleic hydrazide) x 15 ppm (amount of 

impurity hydrazine) = lbs a.i / Acre or gal.

4.0 Residential Exposure and Cancer Risk Estimates

There are residential uses that have been reassessed in this document to reflect updates to HED’s 

2012 Residential SOPs2along with policy changes for body weight assumptions. The revision of 

residential exposures will impact the cancer risk assessment for hydrazine.

4.1 Residential Handler Exposure and Cancer Risk Estimates

The quantitative exposure/risk cancer assessment developed for residential handlers is based on 

consideration of the following scenarios:

Mixer/Loader/Applicator (WDG)

 Manually pressurized handwand sprayer

 Hose-end sprayer

 Backpack Sprayer

Note: For the cancer assessment calculations, the manually pressurized handwand sprayer was 

used, as it was the most conservative and protective of the hose-end and backpack sprayer 

scenarios.

Residential Handler Exposure Data and Assumptions

A series of assumptions and exposure factors served as the basis for completing the residential 

handler cancer risk assessments. Each assumption and factor is detailed below.

Application Rate: The application rate used in all residential cancer calculations are based on the 

residential turf rate provided in Table 3.1. 

Unit Exposures and Area Treated or Amount Handled:

 

2 Available: http://www.epa.gov/pesticides/science/residential-exposure-sop.html
Page 7 of 17

Unit exposure values and estimates for area treated or amount handled were taken from HED’s 

2012 Residential SOPs3.

Exposure Duration: 

Residential handler exposure is expected to be short-term in duration. Intermediate-term 

exposures are not likely because of the intermittent nature of applications by homeowners.

Days per Year of Exposure: 

It was assumed that residential handlers would apply the product 2 days/year.

Years per Lifetime of Exposure:

It is assumed that residential handlers would be exposed for 50 years out of a 78 year lifespan.

Residential Handler Exposure and Risk Estimate Equations

The algorithms used to estimate exposure and dose for residential handlers can be found in 

Appendix A and/or the 2012 Residential SOPs4.

Summary of Residential Handler Exposure Estimates

Absorbed daily dose (ADD) estimates were calculated for dermal and inhalation exposure 

associated with residential application to turf, and are summarized in Table 4.1.

Table 4.1. Residential Handler Exposure Estimates for Hydrazine.

Exposure

Scenario

Dermal 

Unit 

Exposure 

(mg/lb ai)

Inhalation 

Unit 

Exposure 

(mg/lb ai)

Maximum 

Application 

Rate1

(lb ai/gal)

Amount 

Handled 

Daily2

Dermal Inhalation

Absorbed 

Daily Dose 

(mg/kg/day)3

Absorbed Daily 

Dose 

(mg/kg/day)3

Mixer/Loader/Applicator

Manually 

Pressurized 

Handgun:

(Lawns/Turf)

69 1.1 0.00001 5 gal 4.4 x 10-5 6.9 x 10-7

1. Application rate calculated: max application rate (0.675 lb maleic hydrazide/gal) x 15 ppm (amount of impurity hydrazine) = lbs a.i / gal.

2. Based on HED’s 2012 Residential SOPs (http://www.epa.gov/pesticides/science/residential-exposure-sop.html).

3. Absorbed Daily Dose (Dermal or Inhalation) = Unit Exposure (mg/lb ai) × Application Rate (lb ai/gal) × Amount Handled (gallons/day) × 

Absorption Factor (assumed 100%) ÷ Body Weight (80 kg).

Dermal and inhalation Lifetime Average Daily Doses (LADD) were estimated by adjusting the 

ADD for the number of days/year and number of years in a lifetime of exposure. Cancer risk 

estimates were calculated using a linear low-dose extrapolation approach in which the LADD 

was compared with a Q1* that has been calculated for hydrazine based on dose response data in 

the appropriate toxicology study (Q1* = 3.00 (mg/kg/day)-1. The algorithms used to estimate the 

LADD and cancer risk for residential handlers can be found in Appendix B.

 

3 Available: http://www.epa.gov/pesticides/science/residential-exposure-sop.html

4 Available: http://www.epa.gov/pesticides/science/residential-exposure-sop.html
Page 8 of 17

 Dermal LADD = ADD (mg/kg/day) x 2 appl. / 365 days / year x 50 (years: exp 

duration) / 78 years (lifetime)

 Inhalation LADD = ADD (mg/kg/day) x 2 appl. / 365 days / year x 50 (years: exp 

duration) / 78 years (lifetime)

 Total LADD = Dermal LADD + Inhalation LADD 

 Cancer = Q* x Total LADD 

Summary of Residential Handler Cancer Exposure and Risk Estimates

Table 4.2. Residential Handler Cancer Exposure and Risk Estimates for Hydrazine. "Most Conservative 

Scenario"

Exposure Scenario ADD1

(mg/kg/day)

LADD2

(mg/kg/day)

Total LADD

(mg/kg/day)3 Cancer Risk Estimate4

Manually Pressurized 

Handwand

(Turf)

Dermal

4.4 x 10-5

Dermal

1.55 x 10-7

1.57 x 10-7 4.71 x 10-7

Inhalation

6.9 x 10-7

Inhalation

2.42 x 10-9

1. From Table 4.1.

2. LADD (mg/kg/day) = ADD (dermal or inhalation) (mg/kg/day) × [Days per year of exposure (2 days/yr) ÷ 365 days/year] × [Years per 

lifetime of exposure (50 yrs) ÷ Lifetime expectancy (78 yrs)].

3.

4. Total LADD (mg/kg/day) = Dermal Handler LADD (mg/kg/day) + Inhalation LADD (mg/kg/day).

5. Cancer risk estimates = Total LADD (mg/kg/day) * Q1

*

, where Q1

* = 3.0 (mg/kg/day)-1

.

 

5.2 Residential Post-application Exposure/Risk Estimates

There is the potential for post-application exposure to hydrazine for individuals exposed as a 

result of being in an environment that has been previously treated with maleic hydrazide. The 

quantitative cancer/risk assessment for residential post-application exposures is based on the 

following scenario: 

• Adult Golfer

Note: Because label directions indicate the turf use is an edging use (e.g., along fence rows), and

specific spot treatment (e.g., ant mounds) for which exposure is expected to be low, the “Adult 

Golfer” scenario was assessed and considered to be protective of other scenarios.

Residential Post-application Cancer Exposure and Risk Estimate Equations

As was done for residential handlers, post-application cancer risk estimates were calculated 

using a linear low-dose extrapolation approach in which a LADD is first calculated and then 

compared with a Q1* that has been calculated for hydrazine based on dose response data in the 

appropriate toxicology study (Q1* = 3.0 (mg/kg/day)-1). The algorithms used to estimate the 

LADD and cancer risk for residential post-application exposure can be found in Appendix B.
Page 9 of 17

Average Daily Dermal Dose (ADD) (mg/kg/day) = 

TTR (μg/cm2) x 0.001 (mg/μg) x TC (cm2/hr) x ET (hr/day) 

 BW (kg)

Where:

Average Daily Dermal Dose = Dermal exposure on day of application attributable for activity in a 

previously treated area (mg/kg/day)

TTR = Turf Transferable Residue based on 0-day application (1.35 x 10-5 μg/cm2) 

(Estimated based on assumption that 1% of the application rate of maleic 

hydrazide, adjusted for impurity hydrazine, is available for transfer)

TC = Transfer Coefficient (3,500)

ET = Exposure Time (hours) (4)

BW = Body Weight (kg) (80)

ADD = 2.36 x 10-6

Life Average Daily Dose (LADD) = ADD (mg/kg/day) x 1 day. x 50 years (Expo Duration) 

 365 days 78 lifetime years

Summary of Residential Post-application Cancer Risk Estimates

Table 5.2. Residential Post-application Cancer Exposure and Risk Estimates for Hydrazine.

Lifestage Post-application Exposure Scenario Dermal LADD

(mg/kg/day)1,2

Cancer Risk 

Estimate4

Adult Golfer Dermal 4.14 x 10-9 1.24 x 10-8

1 Dermal LADD (mg/kg/day) = Dermal ADD (2.36 x 10-6 mg/kg/day) × [Days per year of exposure (1 day/yr) ÷ 365 days/year] × [Years per 

lifetime of exposure (50 yrs) ÷ Lifetime expectancy (78 yrs)].

2 Cancer risk estimates = Total LADD × Q1

*

, where Q1

* = 3.0 (mg/kg/day)-1

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

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

cancer assessment was performed for a residential handler using a “pressurized handgun. This 

exposure scenario is representative of a worse case inhalation (volatilization) exposure and may 

be considered protective.

5.3 Combined Residential Risk Estimates (Multiple Exposure Scenarios)

The combined residential risk calculations were generated for this assessment with the 

understanding that a residential handler could use a manually pressurized handwand on 

residential turf, then play golf on a course that was also treated with maleic hydrazide on the 

same day. Therefore, these two exposure scenarios were combined and cancer and risk exposure 

estimations were calculated. See table 5.3 for details.
Page 10 of 17

Table 5.3 Residential Combined (Multiple Exposure Scenarios) Cancer Risk Estimates for Hydrazine.

Combined Exposure 

Scenario Lifestage Exposure Scenario Route of Exposure LADD

(mg/kg/day)1

Combined 

Total LADD

(mg/kg/day)2

Combined 

Total Cancer 

Risk Estimate3

Outdoor Scenario 

(Turf/Golf) Adult

Handler: Turf – Sprays

“Spot and Band”

Dermal 1.55 x 10-7

1.62 x 10-7 4.85 x 10-7

Inhalation 2.42 x 10-9

Post-application: Turf – Golf

“Rough, Tees, Greens” Dermal 4.14 x 10-9

1 LADD (mg/kg/day) taken from Tables 4.2 and 5.2.

2 Combined Total LADD (mg/kg/day) = combined dermal + inhalation LADD for handlers and Adult golfers. 

3 Combined Total Cancer Risk Estimate = Combined Total LADD (mg/kg/day) × Q1

*

, where Q1

* = 3.0 (mg/kg/day)-1
Page 11 of 17

5.4 Spray Drift

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

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

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

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

Lead Agencies for pesticide regulation and other parties to develop the best spray drift 

management practices (see the Agency’s Spray Drift website for more information5. 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 risk estimates associated with drift.

6.0 Occupational Exposure and Cancer Risk Estimates

6.1 Occupational Handler Exposure Cancer Risk Estimates

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

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

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

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

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

manner specific to each application event. 

Based on the anticipated use patterns and current labeling, types of equipment and techniques 

that can potentially be used, occupational handler exposure is expected from the proposed uses. 

This screening-level quantitative exposure/risk assessment, developed for occupational handlers,

is based on the following scenario because it has the highest exposure potential and is protective 

of the other possible application scenarios: 

Occupational Handler Exposure Scenarios

Mixer/ Loader: Water Dispersible Granular (WDG)

 Aerial (for application to high-acreage crops)

Occupational Handler Exposure Data and Assumptions

A series of assumptions and exposure factors served as the basis for completing the occupational 

handler Cancer risk assessments. Each assumption and factor is detailed below on an individual 

basis.

Unit Exposures:

 

5 Available: http://www.epa.gov/opp00001/factsheets/spraydrift.htm 
Page 12 of 17

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

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

PHED 1.1, the AHETF database, the Outdoor Residential Exposure Task Force (ORETF) 

database, or other registrant-submitted occupational exposure studies. Some of these data are 

proprietary (e.g., AHETF data), and subject to the data protection provisions of FIFRA. The 

standard values recommended for use in predicting handler exposure that are used in this 

assessment, known as “unit exposures”, are outlined in the “Occupational Pesticide Handler Unit 

Exposure Surrogate Reference Table6”, which, along with additional information on HED policy 

on use of surrogate data, including descriptions of the various sources, can be found at the 

Agency website7.

The unit exposures used in this conservative estimate were based on “baseline” attire (i.e., no 

gloves or respirator):

- Dermal: 0.227 mg/lb ai 

- Inhalation : 0.00896 mg/lb ai 

Area Treated or Amount Handled: 

For this cancer assessment, the “Fallow Land” exposure scenario proved to be the most 

conservative, therefore the area treated and amount will reflect this scenario exclusively.

For the fallow land application; labels did not specify which crops this product was to be used, 

noting only that “Silverleaf Nightshade” was the targeted perennial weed. Therefore, the 

assessment used a conservative exposure scenario (aerial for 1200 acres) for all calculations. 

This assumption may or may not represent the actual activity, however is protective of all other 

exposure scenarios.

Fallow Land: 

 Aerial Application

 1200 Acres treated

 Application rate: 0.00018 lb ai/A

Exposure Duration:

The fallow land application as well as most of the other occupational exposure scenarios occur 

one time a year. Typically either in the spring or fall. In the case for fallow lands, a single postharvest application is applied for the suppression of weeds, predominately the “Silverleaf 

Nightshade” perennial weed. 

 

Mitigation/Personal Protective Equipment: 

Estimates of dermal and inhalation exposure may be calculated for various levels of personal 

protective equipment (PPE). Results are presented for “baseline,” defined as a single layer of 

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

no respirator.

Days per Year of Exposure:

 

6 Available: http://www.epa.gov/opp00001/science/handler-exposure-table.pdf

7 Available: http://www.epa.gov/pesticides/science/handler-exposure-data.html
Page 13 of 17

To assess cancer risk, it is assumed that private growers would be exposed 10 days per year and 

commercial applicators would be exposed 30 days per year. The term “private grower” means 

that the grower or one of the workers would apply the pesticides to land owned or operated by 

the grower. Commercial applicators means the applicators are completing multiple applications 

for multiple clients.

Years per Lifetime of Exposure: 

It is assumed that handlers would be exposed for 35 years out of a 78 year lifespan.

Summary of Occupational Handler Cancer Exposure and Risk Estimates

Table 6.1.2. Occupational Handler Cancer Exposure and Risk Estimates for Hydrazine. 

Crop or 

Target

Exposure 

Scenario

Private Handler Commercial Handler

LADD (mg/kg/day)1

Total 

LADD3

Cancer 

Risk 

Estimate4

LADD (mg/kg/day)1

Total 

LADD2

Cancer 

Risk 

Estimate Dermal Inhalation Dermal Inhalation 3

“Fallow Land”

Silverleaf

Nightshade

Weed

Aerial

Mixer/

Loader

7.54 x 10-6 2.99 x 10-7 7.83 x 10-6 2.35 x 10-5 2.26 x 10-5 8.96 x 10-7 2.35 x 10-5 7.0 x 10-5

1. LADD (mg/kg/day) = Dose (mg/kg/day) × [Days per year of exposure (10 days for private grower; 30 days for commercial/yr) 

÷ 365 days/year] × [Years per lifetime of exposure (35 yrs) ÷ Lifetime expectancy (78 yrs)].

Where: Dose (mg/kg/day) = [Unit exposure (dermal: 0.227 mg/lb ai; inhalation: 0.00896 mg/lb ai) x Application Rate 

(0.00018 lb ai/A) x Area treated (1200 acres)] / Body weight (80 kg)

2. Total LADD (mg/kg/day) = Dermal LADD (mg/kg/day) + Inhalation LADD (mg/kg/day).

3. Cancer risk estimates = Total LADD × Q1*, where Q1* = 3.0 (mg/kg/day)

6.2 Occupational Post-application Exposure and Cancer Risk Estimates

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

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

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

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

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

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

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

6.2.1 Occupational Post-application Inhalation Exposure and Cancer Risk Estimates

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

assessment was not performed for hydrazine at this time primarily because of the low proposed 

use rate (Tobacco at 0.00018 lb ai/acre). However, there are multiple potential sources of postapplication inhalation exposure to individuals performing post-application activities in 

previously treated fields. These potential sources include volatilization of pesticides and 

resuspension of dusts and/or particulates that contain pesticides. The Agency sought expert 

advice and input on issues related to volatilization of pesticides from its Federal Insecticide, 

Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, and 
Page 14 of 17

received the SAP’s final report on March 2, 20108. The Agency is in the process of evaluating 

the SAP report as well as available post-application inhalation exposure data generated by the 

ARTF and may, as appropriate, develop policies and procedures, to identify the need for and, 

subsequently, the way to incorporate occupational post-application inhalation exposure and thus 

cancer exposure, if needed, into the Agency's risk assessments. If new policies or procedures 

are put into place, the Agency may revisit the need for a quantitative occupational postapplication inhalation cancer exposure assessment for hydrazine.

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

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

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

in higher exposure than post-application inhalation exposure from volatilization. Therefore, it is 

expected that these handler inhalation cancer estimates would be protective of most occupational 

post-application inhalation exposure scenarios.

6.2.2 Occupational Post-application Dermal Exposure and Cancer Risk Estimates

Occupational Post-application Dermal Exposure Data and Assumptions

Hydrazine, via maleic hydrazide, is applied once a year, during non-harvest time frames, as a 

growth inhibitor. In this assessment, tobacco was the crop representing the most conservative 

post-application exposure scenario because of the combination of application rate and transfer 

coefficient. It is applied once a year to the top 1/3 of the tobacco plant or when the harvestable 

leaves or not present. 

A series of assumptions and exposure factors served as the basis for completing the occupational 

post-application cancer risk assessment. Each assumption and factor is detailed below on an 

individual basis:

Transfer Coefficients (TCs):

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

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

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

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

coefficients”, are presented in the ExpoSAC Policy 39” which, along with additional information 

about the ARTF data, can be found at the Agency website10. 

 

8 Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html

9 Available: http://www.epa.gov/pesticides/science/exposac_policy3.pdf

10 Available: http://www.epa.gov/pesticides/science/post-app-exposure-data.html
Page 15 of 17

Table 6.2.2.1. Anticipated Post-Application Activities and Dermal Transfer Coefficients.

Proposed Crops

Policy Crop 

Group 

Category

Crop 

Height

Foliage 

Density

Transfer 

Coefficients 

(cm2/hr)

Activities

Tobacco NA High Full 1900 Hand set irrigation

Application Rate:

Tobacco: 0.00018 lb ai/A

Exposure Time: 

The average occupational workday is assumed to be 8 hours. 

Dislodgeable Foliar Residues (DFR): 

Chemical-specific dislodgeable foliar residue data have not been submitted for maleic hydrazide, 

or for the impurity hydrazine. Therefore, this assessment uses HED’s default assumption that 

25% of the application rate is available for transfer on day 0 following the application, and the 

residues dissipate at a rate of 10% each following day.

For tobacco, “Day 0” residues were estimated to be 0.000504 μg/cm2.

Days per Year of Exposure:

One day a year was used in the LADD calculations because there is only one application per year 

and re-entry for irrigation is only expected once before the residues dissipate.

 

Years per Lifetime of Exposure: 

HED assumes that post-application workers would be exposed for 35 years out of a 78 year 

lifespan.

Restricted Entry Interval

Labels stipulate a 12 - 48 hr. REI.

Occupational Post-application Cancer Dermal Risk Estimates

Table 6.2.2.3. Occupational Post-Application Cancer Risk Estimates for Hydrazine

Crop 

Grouping/Crop Activity Days After Treatment

Dermal LADD 

(mg/kg/day)1

Cancer Risk 

Estimate2

Tobacco Handset irrigation 0 1.18 x 10-7 3.53 x 10-7

1. Dermal LADD (mg/kg/day) = Dermal dose (0.000096 mg/kg/day) × [Days per year of exposure (1 day/yr) ÷ 365 days/year] × [Years per 

lifetime of exposure (35 yrs) ÷ Lifetime expectancy (78 yrs)].

Where: Dermal dose (mg/kg/day) = [DFR (0.000504 μg/cm2) x TC (1900 cm2/hr) x conversion factor (0.001 mg/μg) x 8 hrs/day] / BW (80 kg)

2. Cancer risk estimate = Dermal LADD (mg/kg/day) × Q1

*

, where Q1

* = 3.0 (mg/kg/day)-1

.
Page 16 of 17

Appendix A. Summary of Occupational and Residential Non-cancer Algorithms

Handler Exposure Calculations

 

Daily dose values are calculated using relevant application parameters (i.e., rate and area treated) 

along with unit exposures. Exposures are then adjusted for body weight and absorption factors 

as appropriate to calculate dose levels.

Daily Exposure: The daily exposures were calculated as described below. 

Daily dermal and inhalation exposure (mg/day) for residential pesticide handlers, for a given 

formulation-application method combination, is estimated by multiplying the formulationapplication method-specific unit exposure by an estimate of the amount of active ingredient 

handled in a day, using the equation below:

E = UE * AR * A

where:

E = exposure (mg/day);

UE = unit exposure (mg/lb ai);

AR = application rate (e.g., lb ai/ft2, lb ai/gal); and

A = area treated or amount handled (e.g., ft2/day, gal/day).

Daily Dose: The daily dose (inhalation) was calculated by adjusting the daily inhalation 

exposure values by body weight and accounting for inhalation absorption. For adult handlers, an 

average body weight of 80 kg was used.

The daily doses are calculated using the following formula:

ADD= 

E * AF

BW

where:

ADD = average daily dose absorbed in a given scenario (mg ai/kg/day),

E = exposure (mg ai/day),

AF = absorption factor (dermal and/or inhalation), and

BW = body weight (kg).

Appendix B. Summary of Occupational and Residential Cancer Algorithms
Page 17 of 17

After the development of the ADD values, the next step required to calculate carcinogenic risk 

estimates is to amortize these values over the anticipated lifetime, which results in the LADD. 

LADD values are calculated using the following equation:

LADD = ADD * 

Days per Year of Exposure

365 Days per Year * 

Years per Lifetime of Exposure

Lifetime Expectancy

where:

LADD = absorbed dose over a lifetime (mg ai/kg/day),

ADD = average daily dose absorbed in a given scenario (mg 

ai/kg/day),

Days per Year of Exposure = annual frequency of an application by an individual 

(days/year),

Years per Lifetime of Exposure = amount of a lifetime that an individual would be 

expected to use pesticides (years), and

Lifetime Expectancy = average life expectancy of an individual (years).

Cancer risk estimate calculations are completed by comparing the LADD values calculated 

above to the Q1* for the chemical. Cancer risk estimates are calculated using the following 

equation:

Total Cancer Risk Estimate = (Dermal LADD + Inhalation LADD) * Q1*

where:

Cancer Risk Estimate = probability of incidence of cancer cases over a lifetime (unitless),

Dermal LADD = absorbed dose from dermal exposure over a lifetime (mg ai/kg/day),

Inhalation LADD = absorbed dose from inhalation exposure over a lifetime (mg

ai/kg/day), and

Q1* = quantitative dose response factor used for linear, low-dose response 

cancer risk estimate calculations (mg/kg/day)-1.