UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASH I NGTON, D.C. 20460

OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION

Date: June 20, 20 1 4

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 Garl i c in dormant turf.

PC Code: 05150 I /Ma l eic Hydrazide Decision No.: 481781 Petition No. : NA

Risk Assessment Typ e : Occupatio n al/Residential Cancer Exposure Assessment TXRNo.:NA DP Barcode: 420405 Registration No

. : NA Regulatory Action: Reg i strat i on Review Case No.: 0381

CASNo.: 123-33-1

Fr om: 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 Hea l t h 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 17Table of Contents

1.0 Execu t ive Summary

......................... .. ......................... ..... ..................... ...... ............... .......... 3 2.0 Hazard Characterization

....................................................................................................... 4 3.0 Use Profi le

. . ......... .. ............ . .......... ..... ......... .. .. . ........... . ........... . .......... .. .. . ...... . ...................... 4 4. 0 R esident ial Exposure an d Cancer Risk Es tim ates

................. .. ........................................ .... 6 4.1 R eside ntial Handler Ex posur e and Cance r Risk Estimates

. ............................................. 6 5.2 Residential Post-application Exposure/ Ri sk Estimates

............. . ........ . .......... .. ........... .. .... 8 5.3 Com bi ne d Residential Risk Est imat es (Multiple Ex p osure Scenarios)

........................... 9 5.4 Spray Drift

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

...... .......... .. ...... .. ... . ............................ 1 1 6.1 Occupational Handler Exposure Cancer Risk Esti m ates

............................................... 11 6.2 Occupational Post-application E xpo s ure and Canc er Ri s k Estimates

.. .......... .. .. .. ........ . 1 3 6.2 .1 Occupationa l Post-application Inhalation Exposure and Cance r Risk Estimates

... 13 6.2.2 Occupational Post-application Derm al Exposure and Cancer Ri sk Est imate s

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

................. .... 16 Append i x B. Summary of Occupational and Resi d ent i al Cancer Algo rithm s

.............................**~**

Page 2 of 17Page 3 of 17

1.0 Executive Summary

Although toxic ological endpoints of concern have not been identified for the maleic hydrazide human health assessment , an occupational and residential exposure assessment was co nducted for the impurity, hydrazine . The impurity hydrazine is a carcinogen, with a Q 1 * 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 conclusi on 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 hydr azine limit

. Maleic hydrazide potassium salt (parent compound)

, and consequently its impurity h ydrazine

, is used both in occupational and residential setting s

. 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 othe r undesirable weeds in terrestrial no nfood crops, on fallow land, industrial areas and along road sides and other rights

- of

- way. Application equipment includes groundboom, backpack and mechanically pre ssurized handgun sprayers, and fixed wing aircraft

. Residential uses include applications to control wild garlic and wild onions in dormant turf grass 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.

Occupa tional and r esidential a pplication 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 t he occupational and residential sections that follow.

Personal p rotecti ve e quipment (PPE) required on the labels include long

- sleeved shirt, long pants, chemical resistant gloves, shoes and socks. Labels also not e the restricted entry interval (REI) is 1 2

- 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 Resi dential 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 h ave included review by the Human Studies Review Board. Descriptions of data sources, as well as guidance on their use, can be found at the Agency website 1

.

1 http://www.epa.gov/pesticides/science/handler

- exposure

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

- app

- exposure

- data.htmlPage 4 of 17

2.0 Hazard Characterization

The toxicological database for maleic hydrazide is complete and suffici ent 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. T herefore, 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 clas sified 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 fo r 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 f

or hydrazine is 3.0 (mg/kg/day)

- 1 using the l inearized 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 Directio ns for Use of Maleic H ydrazide 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. Rat e (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 WD G:

EPA Reg. No. 400

- 165 0.00014

(registrant provided) 1 0. 0001 4 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 af ter initial applicatio n is made

. 12

- 48 hr. REI

Use Site 2Page 5 of 17

Table 3.1. Summary of Directio ns for Use of Maleic H ydrazide 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. Rat e (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 WD G:

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 WD G:

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 WD G:

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 installati ons, 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 /ga l) (registrant provided) 2 0.000020 (lbs ai /ga l) N/A

Use Site 5
Ornamental Shrubs and Trees: Manually Pressurized Handgun, Backpack
sprayer WD G:

EPA Reg. No. 400

- 165 0.0000006

( lbs ai/ga l) 1 0.0000006 ( lbs a.i. / ga l) NA Apply to plants that have recently been pruned. Apply
once a year

Use Site 6Page 6 of 17

Table 3.1. Summary of Directio ns for Use of Maleic H ydrazide 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. Rat e (lb a

. i

. /A)

or (lbs a.i. / gal) PHI

(days) Use Directions and

Limitations

Fallow Land:
G roundboom, Aerial, Manually Pressurized Handgun WD G:

EPA Reg. No. 400

- 165 0.000 18 1 0.000 18 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 Estimate s

T here are residential uses that have been reassessed in this document to reflect updates to HED’s 2012 Residential SOPs 2 along with policy changes for body weight assumptions. The revision of residential exposures will i mpact the cancer risk assessment for h ydrazine

.

4 .1 Residential Handler Exp osure 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)

 M anually pressurized h andwand sprayer

 Hose

- end sprayer

 Backpack Sprayer

Note: For the cancer assessment calculations, the manually pressurized ha ndwand 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 applicati on rate used in all residential cancer calculations are based on the residential turf rate provided in T able 3. 1.

Unit Exposures and Area Treated or Amount Handled :

2 Available: http://www.e pa.gov/pesticides/science/residential

- exposure

- sop.htmlPage 7 of 17

Unit exposure values and estimates for area treated or amount handled were taken from HED’s 2012 Residential SOPs 3

.

Ex posure 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 Y

ear 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 SOPs 4

. Summary of Residential Handler Exposure Estimates

Absorbed daily dose (ADD) estimates were calculated for dermal and inha lation 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 Rate 1 ( lb ai /gal) Amount

Handled Daily 2 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 Dose s (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 a pproach in which the LADD

was compared with a Q 1 * that has been calculated for h ydrazine based on dose response data in the appropriate toxicology study (Q 1 * = 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.htmlPage 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

Tabl e 4. 2

. Residential Ha ndler Cancer Exposure a nd Risk Estimates for Hydrazine

. "Most Conservative Scenario"

Exposure Scenario ADD 1 (mg/kg/day) LADD 2

(mg/kg/day) Total LADD

(mg/kg/day) 3 Cancer Risk Estimate 4

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) * Q 1 * , where Q 1 * = 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 m aleic h ydrazide

. The quantitative cancer

/risk assessment for residential post

- application exposures is based on the following scenario :

• Adult Golfer

No te: 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

- ap plication cancer risk estimates were calculated using a linear low

- dose extrapolation approach in which a LADD is first calculated and then compared with a Q 1 * that has been calculated for h ydrazine based on dose response data in the appropriate toxicology study (Q 1 * = 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 7 8 lifetime years

Summary of Residential Post

- application Cancer Risk Estimates

Table 5

. 2

. Residential Post

- application Cancer Exposure a nd Risk Estimates for Hydrazine

. Lifestage Post

- application Exposure Scenario Dermal LADD (mg/kg/day) 1,2 Cancer Risk Estimate 4

Adult Golfer Dermal 4. 14 x 10

- 9 1. 2 4 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 × Q 1 * , where Q 1 * = 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 ( volati li zation ) exposure and may be considered protective

.

5 .3 Combined Residential R isk 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. Theref

ore, 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 Hydrazi n e . 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 Estimate 3

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) × Q 1 * , where Q 1 * = 3.0 (mg/kg/day)

- 1Page 11 of 17

5

. 4 Spray Drift

Spray drift is always a potential source of exposure to residents nearby to spraying operat ions. 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, EP A 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 information 5

. 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, orcha rd 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 dis tinct 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 pr otection 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 handl er exposure is expected from the proposed uses. Th is 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 oth er possible application scenario s:

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/spra ydrift.htmPage 12 of 17

It is the policy of HED to use the bes t 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 reg istrant

- 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

a ssessment, known as “unit exposures”, are outlined in the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table 6 ”, which, along with additional information on HED policy on use of surrogate data, including descriptions of the various sour ces, can be found at the Agency website 7

. 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 : 0.0 0896 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 pro duct 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 l and application as well as most of the other occupational exposure scen arios occur one time a year. Typically either in the spring or fall. In the case for fallow lands, a single post

harvest 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.htmlPage 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 LADD 3 Cancer

Risk Estimate 4 LADD (mg/kg/day) 1 Total LADD 2 Cancer

Risk Estimate 3 Dermal Inhalation Dermal Inhalation

“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) = D ose (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. 0 0896 mg/lb ai) x Application Rat e (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 = To tal 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 re

entry 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 o n suc h 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 great ly 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

a ssessment was not perform ed 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 post

application inhalation exposure to individuals performing post

- application activities in previously treated fields. These potential sources include volatilization of pesticides and resuspension of d usts 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, an dPage 14 of 17

received the SAP’s final report on March 2, 2010 8

. 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 r evisit the need for a quantitative occupational post

application 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
exp ected that these handler inhalation cancer estimates would be protective of most occupational post

- application inhalation exposure scenarios.

6

. 2 .2 Occupational P ost

- 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, t obacco was the crop representing the most conservative post

- application exposure scen ario 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 fo r 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 chemical

specific data, are derived from ARTF exposure monitoring studies, and, as proprietary data, are subject to the data protection provisions of FIFRA. The standard values recommended for use in predicting post

- application exposure that are used in this assessment, known as “transfer coefficients”, are presented in the ExpoSAC Policy 3 9 ” which, along with additional information about the ARTF data, can be found at the Agency website 10

.

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/s cience/post

- app

- exposure

- data.htmlPage 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 (cm 2 /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 d ata hav e not been submitted for maleic h ydrazid e , 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/cm 2

.
Days per Y

ear of E xposure : 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

Estimate 2

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/cm 2 ) x TC (1900 cm 2 /hr) x conversion factor (0.001 mg/μg) x 8 hrs/day] / BW (80 kg)
2

. Cancer risk estimate = Dermal LADD (mg/kg/ day) × Q 1 * , where Q 1 * = 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 formulation

application 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/ft 2 , lb ai/gal); and A = area treated or amount handled (e.g., ft 2 /day, gal/day).

Daily Dose : The daily d ose (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 fo rmula:

ADD= E * AF
BW

where:

ADD = average daily dose absorbed in a given scenario (mg ai/kg/day), E = e xposure (mg ai/day), AF = absorption fa ctor (dermal and/or inhalation), and BW = body weight (kg).

Appendix B. Summary of Occupational and Residential Cancer AlgorithmsPage 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 a re 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).

C ancer risk estimate calculations a re completed by comparing the LADD values calculated above to the Q 1 * for the chemical . Cancer risk estimate s a re calculated using the following equation:

Total Cancer Risk Estimate = ( Dermal LADD + Inhalation LADD ) * Q 1 *

w here:

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 Q 1 * = quantitative dose response factor used for linear, low

- dose response cancer risk estimate calculations ( mg/kg/day)

- 1

.