Date: 

Subject: 

November 26,2014 

Daminozide. Draft Occupational and Residential Exposure/Risk Assessment for 

Registration Review. 

PC Code: 035101 

Decision No.: 478436 Petition No.: NA 

DP Barcode: 424016 

Registration No.: NA 

Regulatory Action: Reg Review DRA 

Risk Assessment Type: Exposure Assessment Case No.: 0032 

TXRNo.:NA CAS No.: 1596-84-5 

MRID No.: 49013500 40CFR:NA 

From: 

Through: 

To: 

Introduction 

Zaida Figueroa, M.S., Industrial Hygienist Risk Assessment Branch II 

Health Effects Division (7509P) 

Christina Swartz, Branch Chief 

Risk Assessment Branch II 

Health Effects Division (7509P) 

and 

Margaret Hathaway, Chemical Review Manager 

Pesticide Re-Evaluation Division (7508P) 

The Pesticide Re-evaluation Division (PRD) requested that Health Effects Division (HED) 

conduct an occupational exposure/risk assessment to estimate the risk to human health that will 

result from the current actively registered uses of daminozide. This memorandum contains 

HED's occupational/residential exposure and risk assessment required during registration review 

to reflect the updated daminozide's hazard assessment, science policies and procedures. There 

are no registered residential uses; therefore, this risk assessment only addresses potential 

occupational exposures associated with the daminozide's registered uses. 

Page 1 of19 
Note: This memorandum was reviewed by the Exposure Science Advisory Committee 

(ExpoSAC) on November 06,2014. 

Page 2 of19 
2.4 Data Deficiencies and Requirements ............................................................................... 6 

3.0 Hazard Characterization ....................................................................................................... 6 

4.0 Use Profile ............................................................................................................................ 9 

5.0 Residential Exposure and Risk Estimates .......................................................................... 10 

5.1 Residential Post-application Exposure for Ornamentals from Retail Locations ............ 10 

5.2 Spray Drift ...................................................................................................................... 10 

6.0 Occupational Exposure and Risk Estimates ...................................................................... 10 

6.1 Occupational Handler Exposure/Risk Estimates ............................................................ 1 0 

6.1.1 Occupational Non-cancer Handler Exposure/Risk Estimates ................................. 10 

6.1.2 Occupational Cancer Handler Exposure/Risk Estimates ........................................ 11 

6.2 Occupational Post-application Exposure/Risk Estimates .............................................. 12 

6.2.1 Occupational Post-application Inhalation Exposure/Risk Estimates ...................... 13 

6.2.2 Occupational Post-application Non-Cancer Dermal Exposure/Risk Estimates ...... 13 

6.2.3 Occupational Post-application Cancer Dermal Exposure/Risk Estimates .............. 13 

Appendix A. Summary of Occupational Handler and Post-application Cancer Exposure/Risk 

Estimates for UDMH .................................................................................................................... 14 

Appendix B. Summary of Occupational Cancer Algorithms ...................................................... 15 

Appendix C. Summary of the Study (MRID# 49013500): Determination of the Concentration of 

Unsymmetrical Dimethyl Hydrazine (UDMH) in a Mixture ofDaminozide and Water over a 

Storage Period of 24 Hours ........................................................................................................... 1 7 

Page 3 of19 
currently registered uses of daminozide for registration review. HED also considered exposure 

to unsymmetrical dimethyl hydrazine (UDMH), a metabolite/degradate formed by the hydrolysis 

of daminozide. As a degradation product, it exists as a minor impurity in technical and 

formulated products. The UDMH exposure assessment is presented in Appendix A. 

Exposure Profile 

There are three registered daminozide products for treatment of containerized ornamental plants 

grown in commercial greenhouses, shade houses, and outdoor nurseries. There is a potential for 

occupational exposure associated with handler activities (i.e., mixing, loading, and applying), as 

well as post-application exposure is expected for workers re-entering treated areas. Based on the 

use pattern, the duration of exposure is expected to be short-term (1 to 30 days) and 

intermediate-term (1 to 6 months) because: 1) plants grown in commercial greenhouses, shade 

houses, and outdoor nurseries are cyclical, and 2) product applications are expected to be rotated. 

There are no registered residential uses or scenarios that will result in residential exposure; 

therefore, this risk assessment only addresses potential occupational exposures associated with 

the registered uses. 

Hazard Profile 

The toxicology database for daminozide is complete and sufficient for risk assessment purposes. 

The toxicology database also includes toxicity studies conducted on UDMH. No target organs 

for non-cancer effects were identified for daminozide. There was no evidence of susceptibility 

in the developmental and reproduction studies. For short- and intermediate-term dermal and 

inhalation non-cancer occupational exposure, no toxicological endpoints were selected for 

daminozide because no hazard was identified and no effects were observed in the database. 

These dermal and inhalation hazard considerations are considered protective of the UDMH that 

may be formed as a tank mix metabolite/degradate due to the low amount present. 

Daminozide and UDMH were assessed for carcinogenicity under the Agency's previous (1986) 

cancer guidelines and were classified as Group B2 carcinogens (i.e., probable human 

carcinogen). Separate cancer potency (Q*) factors were calculated for each compound. For 

daminozide a Q* of0.0087 (mg/kg/day)"1 was calculated based on an increased incidence of 

combined lung carcinomas and adenomas in male mice. For UDMH, a Q* of0.46 (mg/kg/day)"1 

was calculated based on an increased incidence of hemangiosarcomas in male mice. Neither 

compound showed evidence of genotoxicity in a battery of assays submitted to the Agency; 

however there are published genotoxicity studies on UDMH showing positive results. 

Page 4 of19 
Non-Cancer Occupational Exposure 

Occupational non-cancer occupational handler and post-application risk estimates were not 

quantitative assessed, because no toxicological endpoints of concern were identified. 

The current 24-hour REI specified on the registered labels is based on a dislodgeable foliar 

residue (DFR) study on apples and chrysanthemums reviewed as part of the reregistration 

eligibility decision (RED) document (MRID No. 40037001). However, since there is no longer a 

dermal toxicological endpoint of concern, the REI should be based on the current acute toxicity 

of the active ingredient. The current toxicity database for daminozide indicates low acute 

toxicity via oral, dermal and inhalation (Category IV) routes of exposure. This compound causes 

mild eye irritation (Category III), and is not a skin sensitizer. Based on the [156 subpart K] 

Worker Protection Standard Statement, a REI of 12 hours is adequate to protect agricultural 

workers from post-application exposures to daminozide. HED recommends that the REI be 

adjusted on the registered labels from 24 hours to 12 hours. 

Cancer Occupational Exposure 

Occupational handler cancer (dermal+ inhalation) risk estimates for daminozide range from 

1x1o-7 to 4x10-5. The occupational post-application dermal cancer risk estimates for daminozide 

range from 6x10-6 to 5x10-5. 

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 AR TF database; and an exposure monitoring degradation 

study (MRID No. 49013500); 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 5 of19 
6x10·6 to 5x10·5. 

2.2 Label Recommendations from Occupational Assessment 

A degradation study (MRID No. 49013500) was submitted by Chemtura Corporation in response 

to the requirements of a generic data call-in. The study confirmed that the degradation to 

UDMH starts immediately after daminozide is mixed with water, and increases steadily during 

the 24 hour storage period. Therefore, the current restriction (i.e., Solutions prepared should 

not be held for more than 24 hours.") on the labels to prevent-workers from exposure to 

increased levels ofUDMH forming in the mixed solutions, is adequate and should remain on the 

registered labels. Also, HED that the REI be adjusted on the registered labels. 

2.3 Label Recommendations from Residential Assessment 

None. 

2.4 Data Deficiencies and Requirements 

There are no data deficiencies or requirements identified for daminozide at this time. 

3.0 Hazard Characterization 

The toxicology database for daminozide is complete and sufficient for risk assessment. No 

target organs for non-cancer effects were identified in subchronic or chronic dietary studies on 

daminozide. Daminozide did not show evidence of neurotoxicity in the rat or immunotoxicity in 

the mouse. No offspring or reproductive toxicity was observed in a two-generation study in the 

rat. Furthermore, the toxicology database for daminozide also includes toxicity studies 

conducted on UDMH, a metabolite/degradate found in daminozide (at 0.005%), as well as a 

minor mammalian metabolite (estimated at 1% of the dose). UDMH is formed by hydrolysis of 

daminozide. The rate of UDMH degradation is approximately 0.1% of the parent and cmitinues 

to increase over time (D411596). 

Both daminozide and UDMH are classified under the previous (1986) Agency cancer guidelines 

as B2, probable human carcinogens, and separate cancer potency factors (Q*) were calculated for 

each compound. The carcinogenicity of both compounds has been extensively reviewed by the 

Agency in three Cancer Peer Reviews and by the Scientific Advisory Panel to the Agency. Both 

compounds have been shown to increase the incidence of vascular and lung tumors in mice. 

Page 6 of19 
1!.-~le ~.t_. Acu~ 

fp*fti PI

QlUe (O,r Jlandn~d'- fiWI 

" '(fte.of 

-- ~~.: ~Me • Results Stud_y/~~ line .. n r:hiJJd,. -" . - :r. 870.1000 Acute Oral LDso, Rat 46164609 LDso => 5000 mglkg 

Category IV 

870.1200 Acute Dermal LDso, Rabbit 46164610 LDso > 5,000 mglkg 

Category IV 

870.1300 Acute Inhalation Toxicity, Rat 46217101 LCso > 2.20 mg/L 

Category IV 

870.2400 Primary Eye Irritation, Rabbit 46164611 Mild irritant 

Category III 

870.2500 Primary Dermal Irritation, Rabbit 46164612 Non-irritant. 

Category IV 

870.2600 Dermal Sensitization, Guinea Pig 46164613 Not sensitizers 

Toxicological PODs Used for Risk Assessment 

For short- and intermediate-term non-cancer dermal and inhalation occupational exposure, no 

endpoints were identified for daminozide. No systemic or local dermal toxic effects were 

observed in a 28-day dermal toxicity study in rats up to the limit dose. In addition, no significant 

findings were observed in a rat 28-day inhalation toxicity study. 

Daminozide and UDMH were assessed for carcinogenicity under the Agency's previous (1986) 

cancer guidelines and were classified as Group B2 carcinogens (i.e., probable human 

carcinogen). Separate cancer potency (Q*) factors were calculated for each compound. For 

daminozide a Q* of 0.0087 (mg/kg/dayt1 was calculated based on an increased incidence of 

combined lung carcinomas and adenomas in male mice. For UDMH, a Q* of 0.46 (mg/kg/dayt1 

was calculated based on an increased incidence of hemangiosarcomas in male mice. Neither 

compound showed evidence of genotoxicity in a battery of assays submitted to the Agency; 

however there are published genotoxicity studies on UDMH showing positive results. 

Summaries of the toxicological doses and endpoints for daminozide and UDMH are summarized 

in Table 3.2. 

Page 7 of19 
(1

30 days) and A dermal risk assessment was not conducted because no hazard was identified for dermal 

Intermediate-term exposure. 

(1- 6 months) 

Inhalation Shortterm (1-30 days) An inhalation risk assessment was not conducted because no hazard was identified for inhalation 

and Intermediate- exposure. 

term (1-6 months) 

Classification: B2 carcinogen, probable human carcinogen (Agency 1986 Cancer Guidelines) 

Cancer (all routes) based on an increase in combined lung and vascular tumors in mice. Cancer potency factor = 

0.0087 (mg!kglday)·1 based on lung tumors in male mice. 

UDMH 

Dermal Short-term A separate risk assessment was not conducted for UDMH. The contribution to exposure from the 

(1- 30 days) and UDMH that is formed as a tank mix degradate is negligible relative to exposure to UDMH formed 

Intermediate-term as a metabolite of daminozide, along with UDMH present as an existing contaminant of 

(1- 6 months) daminozide products. 

Inhalation Short- A separate risk assessment was not conducted for UDMH. The contribution to exposure from the 

term (1-30 days) UDMH that is formed as a tank mix degradate is negligible relative to exposure to UDMH formed 

and Intermediate- as a metabolite of daminozide, along with UDMH present as an existing contaminant of 

term (1-6 months) daminozide products. 

Cancer (oral, Classification: B2 Carcinogen, probable human carcinogen (1986 Cancer Guidelines), based on an increased incidence of vascular and lung tumors in mice. Cancer potency factor = 0.46 dermal, inhalation) (mg/kg/day)-1 based on the incidence of vascular tumors in male mice. 

Q*= cancer potency factors. 

Absorption 

Daminozide is poorly absorbed through the skin. A dermal absorption factor (DAF) of 2% was 

selected for cancer risk assessment based on in vivo dermal absorption study in the rat. The low 

absorption seen in the study is consistent with the lack of systemic or dermal toxicity observed in 

a 28-day dermal toxicity study in the rat. This value is considered to be conservative and an 

upper bound limit, based on selection of the individual animal with the highest absorption. 

Furthermore, an in vivo dermal absorption study was also conducted in male rats using UDMH; a 

DAF of23% was selected for cancer risk assessment and is considered conservative. Since no 

inhalation absorption data are available for these compounds, toxicity by the inhalation route is 

considered to be equivalent to the estimated toxicity by the oral route of exposure. 

Body Weight 

The standard body weight for the general population (80 kg) was used for all exposure scenarios 

covered in this risk assessment since the endpoints selected were not developmental and/or fetal 

effects. 

Page 8 of19 
Based on the current use patterns and current labeling, types of equipment and techniques that 

can potentially be used, occupational handler exposure (i.e., mixing, loading, and applying 

activities), is expected from the registered uses. The duration of exposure is expected to be 

short-term (1 to 30 days) and intermediate-term (1 to 6 months) because: 1) plants grown in 

commercial greenhouses, shade houses, and outdoor nurseries are cyclical, and 2) product 

applications are expected to be rotated. 

The Personal Protective Equipment (PPE) statement on the registered labels require applicators, 

and other handlers to wear: long sleeved shirt, long pants, waterproof gloves, shoes plus socks. 

All the registered product labels have a restricted entry interval (REI) of 24 hours. The currently 

registered products and use directions containing daminozide are listed in Table 4.1. 

Table 4.1. Summary of Directions for End-Use Products ofDaminozide. 

Applic. Timing, 

Type, and Equip. 

Foliar spray 

(directed) to 

containerized plants; 

Handheld 

equipment 

(manuallypressurized 

hand wand, 

backpack, sprayer, 

mechanicallypressurized 

handgun) 

Formulation 

[EPA Reg. No.jl 

Applic. Rate 

(lb ail A) 

MaL Max.No. S 

. easona 1 

Apphc. per A li Rat S 2 pp c. e eason (lb ail A) Use Directions and Limitations2 

Ornamental Plants (greenhouses, shade houses, and nurseries) 

B-Nine SP, • Use 1 gal of diluted solution to cover 200 

Soluble sq. ft area of plants. 

Concentrate (SC), • One single application or 2 split 

85% ai applications at 112 to 2/3 rates are allowed. 

[400-110] 

B-Nine WSG, 

Water Soluble 

Granule (WSG), 

85% ai 0.1-0.75% 

[1,000 to 

1---[_40_0_-4_7_8]_--; 7,500 ppm] 

Dazide 85 WSG, 

Water Soluble 

Granule (WSG), 

85%ai 

[62097-17] 

0.0084-0.063 

lb ai!gal 

Multiple3 Not stated 

• Application intervals are specified by 

plant. 

• Plants should be dry when spray is 

applied. 

• Do not overspray foliage, wait for 18-24 

hours after applying in order to allow 

chemical to enter the plant. 

• Solutions prepared should not be held for 

more than 24 hours. Repeat applications 

can be made at 1-2 week intervals or as 

needed. 

• Do not apply this product in a way that 

will contact workers or other persons, 

either directly or through drift. 

• Only protected handlers may be in the area 

during application. 

1 To prevent Increased levels ofUDMH from formtng In these solutions, the labels for damtnoztde EPs Include the restriction 

statement that "Solutions prepared should not be held for more than 24 hours." 2Special restrictions are applied to Florida (i.e., 

specific months of the year these products can be applied depending on the plant). 3The registered products call for one single or 

two split applications per batch of plants. 

Page 9 of19 
HED notes that there are no direct homeowner applications of daminozide to ornamentals; 

however, there are registered commercial ornamental uses and the treated ornamentals could be 

subsequently purchased at a retail location for use in a residential setting. HED considers postapplication exposure resulting from this scenario to be negligible for the following reasons: 

(1) Considering the time from application in a commercial setting to consumer purchase at a 

retail location, residues are expected to decline significantly. 

(2) Typical activities associated with residential ornamentals (e.g., picking fruit, thinning 

shrubs/bushes) are anticipated to occur at some additional time after purchase and transplant, 

increasing the time for residues to decline. 

(3) In many cases, transplanted trees (especially deciduous trees) may have little to no 

foliage available for contact at the time of purchase and transplanting, thus decreasing the 

potential for dermal exposure. 

Therefore, quantitative residential non-cancer or cancer post-application risk assessments for the 

use of daminozide on commercial ornamentals were not performed. because of the lack of 

potential exposure. In addition, no dermal or inhalation non-cancer toxicological endpoints of 

concern were identified. 

5.2 Spray Drift 

All the daminozide uses were evaluated as part of the Registration Review process to ensure that 

the potential for spray drift from all registered uses have been considered in the risk assessment. 

Based on the use-pattern, HED determined that daminozide is not registered on use sites that 

would result in spray drift. Therefore, a quantitative spray drift assessment was not conducted 

for daminozide. 

6.0 Occupational Exposure and Risk Estimates 

6.1 Occupational Handler Exposure/Risk Estimates 

6.1.1 Occupational Non-cancer Handler Exposure/Risk Estimates 

Although there is potential for occupational non-cancer handler exposure, risk estimates for 

daminozide were not quantitatively assessed because no dermal or inhalation toxicological 

endpoints of concern were identified. No additional PPE recommendations are needed on the 

registered labels. Furthermore, a separate short- and intermediate-term non-cancer dermal and 

Page 10 of19 
(UDMH) in a Mixture ofDaminozide and Water over a Storage Period of24 Hours,

 was 

submitted by Chemtura Corporation in response to the requirements of a generic data call-in for 

the Registration Review of daminozide. The study confirmed that the degradation to UDMH 

starts immediately after daminozide is mixed with water, and increases steadily during the 24 

hour storage period. Therefore, the current restriction (i.e., "Solutions prepared should not be 

held for more than 24 hours.") on the labels to prevent workers from exposure to increased levels 

ofUDMH forming in the mixed solutions, is adequate and should remain in the registered labels. 

A summary of the study is presented in Appendix C. 

6.1.2 Occupational Cancer Handler Exposure/Risk Estimates 

Although a non-cancer risk assessment was not performed due to the lack of adverse effects in 

the non-cancer dermal and inhalation studies, a cancer exposure and risk assessment was 

performed because a cancer potency factor (Q*) was identified. Dermal and inhalation exposure 

does contribute to the overall cancer risk for daminozide. In addition, cancer handler risks of 

UDMH were calculated and are presented in Appendix A. 

The following assumptions are used to assess cancer risk. 

Days per Year of Exposure: 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 in commercial settings. 

Years per Lifetime of Exposure: It is assumed that handlers would be exposed for 35 years out of 

a 78 year lifespan. 

Lifetime Expectancy: Life expectancy values are from the Exposure Factors Handbook 2011 

Edition Table 18-1 (U.S. EPA, 2011). The table shows that the overall life expectancy is 78 

years based on life expectancy data from 2007. In 2007, the average life expectancy for males 

was 75 years and 80 years for females. Based on the available data, the recommended value for 

use in cancer risk assessments is 78 years. 

Occupational Handler Cancer Exposure and Risk Equations Cancer risk estimates were calculated using a linear low-dose extrapolation approach in which a 

Total Lifetime Average Daily Dose (LADD) is first calculated and then compared with a Qr* 

Page 11 of19 
can be found in Appendix B. 

Summary of Occupational Handler Cancer Exposure and Risk Estimates 

An occupational handler cancer assessment was completed for daminozide at label required PPE 

(i.e., long sleeved shirt, long pants, waterproof gloves, shoes plus socks, no respirator). For 

daminozide, the occupational handler cancer risk estimates range from lxl0"7 to 4x10-5 (see 

Table 6.1.2). 

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

Private Handler Commercial Handler 

LADD (mglkg/day) LADD (mglkg/day) 

Crop or Dermal1 . Cancer Exposure Scenario Inhalation1 Total Inhalatio Total Target [Single [No LADJ>l Risk Dermal1 nl LADJ>l Layer/ Estimate4 [SUG] 

.... ' Gloves] Respirator] [NoR] 

Mixer/Loader/Applicator for WDG/Lic uids 

Ornamentals Backpack Sprayer 0.0000867 0.0000542 0.000141 lxl0-6 0.00026 0.000163 0.000424 

Ornamentals 

Ornamentals 

Manually-pressurized 0.00000332 0.0000116 0.000015 lxl0-7 0.00000996 0.0000349 0.000045 Hand wand 

Mecanically-pressurized 0.000486 0.00116 0.00165 lxto-s 0.00146 0.00349 0.00494 Handgun 

1 Dermal LADD (mg/kg/day)- Dermal dose (mglkg/day) x [Days per year of exposure (days/yr) 365 days/year] x [Years per hfetlme of 

exposure (yrs) -T Lifetime expectancy (yrs)]. 

2 Inhalation LADD (mglkglday) =Inhalation Dose (mglkglday) x [Days per year of exposure (days/yr) I 365 days/year] x [Years per lifetime 

of exposure (yrs) -T Lifetime expectancy (yrs)]. 

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

4 Cancer risk estimates= Total LADD x Ot•, where Q1• = 0.0087 (mglkg/day)·1. Cancer risk estimates were calculated at label required PPE. 

6.2 Occupational Post-application Exposure/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 ~xposure. Page 12 of19 

Cancer 

Risk 

Estimate4 

4xio-6 

4xl0"7 

4xi0-5 
The Worker Protection Standard for Agricultural Pesticides contains requirements for protecting 

workers from inhalation exposures during and after greenhouse applications through the use of 

ventilation requirements [ 40 CFR 170.110, (3) (Restrictions associated with pesticide 

applications)]. Those requirements are to be protective of any potential low-level non-cancer 

post-application inhalation exposure that could result from these types of applications. 

6.2.2 Occupational Post-application Non-Cancer Dermal Exposure/Risk Estimates 

Although post-application exposures are expected for workers entering treated greenhouse and/or nursery areas and handling treated ornamental plants, occupational non-cancer post-application 

risk estimates were not quantitative assessed, because no dermal endpoint of concern was 

identified. 

Restricted Entry Interval 

The current 24-hour REI specified on the registered labels is based on a dislodgeable foliar 

residue (DFR) study on and chrysanthemums that was reviewed as part of the 

reregistration eligibility decision (RED) document and judged supplemental (MRID No. 

40037001). However, since there is no longer a dermal toxicological endpoint of concern, the 

REI should be based on the current acute toxicity of the active ingredient. The current toxicity 

database for daminozide indicates low acute toxicity via oral, dermal and inhalation (Category 

IV) routes of exposure. This compound causes mild eye irritation (Category III), and is not a 

skin sensitizer. Based on the [40 CFR 156 subpart K] Worker Protection Standard Statement, a 

REI of 12 hours is adequate to protect agricultural workers from post-application exposures to 

daminozide. HED recommends that the REI be adjusted on the registered labels from 24 hours 

to 12 hours. 

6.2.3 Occupational Post-application Cancer Dermal Exposure/Risk Estimates 

Post-application occupational handler cancer risk estimates were calculated using a linear lowdose extrapolation approach in which a Total LADD is first calculated and then compared with a 

Q1* that has been calculated for daminozide based on dose response data in the appropriate 

toxicology study (Q1* = 0.0087 (mg/kg/dayt1). The algorithms used to estimate the LADD and 

cancer risk for occupational workers can be found in Appendix B. The following assumptions are used to assess cancer post-application risk: 

Days per Year of Exposure: 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 

Page 13 of19 
Edition, the recommended lifespan for use in cancer risk assessments is 78 years. Life 

expectancy values are derived from the Exposure Factors Handbook 2011 Edition Table 18-1 

(U.S. EPA, 2011). The table shows that the overall life expectancy is 78 years based on life 

expectancy data from 2007. In 2007, the average life expectancy for males was 75 years and 80 

years for females. 

Occupational Post-application Cancer Dermal Risk Estimates 

An occupational post-application cancer assessment was completed for daminozide (Table 

6.2.3). The occupational post-application cancer risk estimates range from 6x10-6 to 5x1o-5 . 

Table 6.2.3. Occupational Post-Application Cancer Exposure and Risk Estimates for Daminozide. .. 

.Crop or Target 

Anticipated Activity Days After DermalLADD Cancer Risk 

Transfer Coefficients (cm2/hr) Treatment (mglkglday)1 Estimate2 

Hand Pruning; Scouting; Container 

Moving; Hand Weeding; Grafting; 

Hand Harvesting; Propagating; 0 0.0006 6x10~ Ornamentals/ Transplanting; Pinching; 

Nurseries Tying/Training 

TC=230 cm2/hr 

Irrigation (hand set) 0 . 0.0053 5xi0·5 

TC=I,900 cm2/hr 

Dermal LADD (mglkg/day) =Dermal Dose (mglkg/day) x [Days per year of exposure (days/yr) + 365 days/year] x [Years per 

lifetime of exposure (yrs) +Lifetime expectancy (yrs)]. 

2 Cancer risk estimate= Dermal LADD (mglkg/day) x Q1', where Q1' = 0.0087 (mglkg/day)'1. 

Appendix A. Summary of Occupational Handler and Post-application Cancer 

Exposure/Risk Estimates for UDMH 

Occupational handler cancer assessments were completed for UDMH at label required PPE (i.e., 

long sleeved shirt, long pants, waterproof gloves, shoes plus socks, no respirator). Occupational 

cancer exposures were calculated using the maximum application rate of daminozide (parent) 

multiplied by 0.1% to adjust for the ratio of parent (assuming 100%) to UDMH to account for 

how much degrada:te will be in the tank mix. 

The algorithms used to estimate the LADD and cancer risk for occupational workers can be 

found in Appendix A. A Total LADD was also calculated for UDMH and compared to a Q1 * 

that has been calculated based on dose response data in the appropriate toxicology study (Q1 * = 

0.46 (mg/kg/dayt1). 

Page 14 of19 
Table A.l. Occu1 ational Handler Cancer Exposure and Risk Estimates for UDMH. 

,_,

Private Handler Commercial Handler 

Crop or Target Exposure LADD (mglkg/day) Total Cancer LADD (mglkg/day) Total Cancer Risk Scenario Risk Dermal1 Inhalation2 LADW Estimate4 Dermal1 lnhalation2 LADW Estimate4 

Mixer/Loader/Applicator for WDG/Liquids 

Sprays using 

Ornamentals Backpack 9.97xl0·7 5.42xl0·8 1.05x10-6 sxto·7 2.99x10-6 1. 36xl0·8 3.15x10-6 

Sprayer 

Sprays using 

Ornamentals Manually- 3.82xl0·8 1.16xl0·8 4.99xl0·8 2xlo.s 1.15x10·7 3.49xi0·8 1.50x10·7 pressurized 

Hand wand 

Sprays using 

Ornamentals . Mecanically- 5.58x10-6 1.16x10-6 6.75xl0·6 3xl0-6 1.67x10·5 3.49x10-6 2.02x10·5 pressurized 

Handgun 

1 Dermal LADD (mglk:glday)- Dermal Dose (mglk:glday) x [Days per year of exposure (days/yr) 365 days/year] x [Years per hfet1me of 

exposure (yrs) +Lifetime expectancy (yrs)]. 

2 Inhalation LADD (mglk:glday) =Inhalation Dose (mglk:glday) x [Days per year of exposure (days/yr) I 365 days/year] x [Years per lifetime 

of exposure (yrs) +Lifetime expectancy (yrs)]. 

3 Total LADD (mglk:glday) =Dermal LADD (mglk:glday) + Inhalation LADD (mglk:glday). 

4 Cancer Risk Estimates =Total LADD x Q1", where Q1" = 0.46 (mglk:glday)"1. Cancer risk estimates were calculated at label required PPE. 

Appendix B. Summary of Occupational Cancer Algorithms 

Potential daily exposures for occupational handlers are calculated using the following formulas: 

where: 

E 

UE = 

AR 

A = 

E=UE * AR *A* 0.001 mg/ug 

exposure (mg ai/day), 

unit exposure (Jlg ai/lb ai), 

maximum application rate according to proposed label (lb ai A or lb ail gal), and 

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

Potential daily exposures for occupational post-application workers are calculated using the 

following formulas: 

DFR1=AR * F* (1-D/ * ( 4. 54E8 ;:) * ( 2. 47E-8 

Page 15 of19 

lxl0-6 

7xto-s 

9x10-6 
t 

where: 

E 

TC 

DFRt 

ET 

= 

= 

= 

number of days after application day (days). 

E=TC * DFR t .* ET * 0. 001 mg 

ug 

exposure (mg ai/day), 

transfer coefficient (cm2/hr), 

dislodgeable foliar residue on day "t" (J..Lg/cm2), and 

exposure time (hours/day). 

The daily doses for both occupational handlers and post-application workers are calculated using 

the following formula: 

ADD= 

where: 

E*AF 

BW 

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). 

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: 

where: 

LADD 

ADD 

Days per Year of Exposure Years per Lifo time of Exposure LADD = ADD* ---------* 

365 Days per Year Lifetime Expectancy 

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

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), 

Page 16 of19 
Total Cancer Risk Estimate= {Dermal LADD +Inhalation LADD) * Q1 * 

where: 

Cancer Risk Estimate = 

DermalLADD = 

Inhalation LADD = 

= 

probability of incidence of cancer cases over a lifetime (unitless), 

absorbed dose from dermal exposure over a lifetime (mg ailk:g/day), 

absorbed dose from inhalation exposure over a lifetime (mg 

ailk:g/day), and 

quantitative dose response factor used for linear, low-dose response 

cancer risk estimate calculations (mg/kg/day)"1• 

Appendix C. Summary of the Study (MRID# 49013500): Determination of the 

Concentration of Unsymmetrical Dimethyl Hydrazine (UDMH) in a Mixture of 

Daminozide and Water over a Storage Period of 24 Hours 

The study entitled "Determination of the Concentration of Unsymmetrical Dimethyl Hydrazine 

(UDMH) in a Mixture ofDaminozide and Water Over a Storage Period of24 Hours," was 

submitted by Chemtura Corporation in response to the requirements of a generic data call-in for 

the Registration Review of daminozide (Case No. 0032). 

Summary 

The study entitled "Determination ofthe Concentration of Unsymmetrical Dimethyl Hydrazine 

(UDMH) in a Mixture ofDaminozide and Water over a Storage Period of24 Hours," was 

submitted by Chemtura Corporation in response to the requirements of a generic data call-in for 

the Registration Review of daminozide (Case No. 0032). The purpose of the study was to 

quantify the amount ofUDMH present as an impurity in the formulation, as well as characterize 

its potential for formation after mixing over time. As stated in MRID 490135-00, the study is an 

Adverse Effects Report that was conducted under the requirements found at 40 CFR § Section 

159.179 (a)(2)(i)(D), "Metabolites, degradates, contaminants and impurities." 

This study was designed to determine the concentration of unsymmetrical dimethyl hydrazine 

(UDMH) in a mixture of daminozide (parent) and water over a 24 hour storage period at ambient 

temperature. The daminozide solution was prepared at a concentration of3,750 ppm. Two 

aliquots of the solution were collected and analyzed for UDMH at Time 0 (immediately after 

solution preparation), 1, 2, 4, 6, and 24 hours. 

Page 17 of19 
Degradation to UDMH started immediately after daminozide was mixed with water, and the 

concentration of UDMH rose steadily during the 24 hour storage period. The results show that 

UDMH concentrations in the daminozide solution increased steadily with time. Average UDMH 

concentrations were 0.043, 0.16, 0.36, 0.67, 1.1, and 3.7 mg/L at Time 0, 1, 2, 4, 6, and 24 hours, 

respectively. Expected levels ofUDMH cannot be predicted accurately beyond the 24 hour time 

period. Based on V ersar' s linear regression analysis, the data fit a linear regression model with 

an R2 value of0.998 (see Figure 1). 

The study author compared the UDMH concentration at each storage period after dilution to 

those concentrations occurring immediately after solution preparatfon (Time 0) using at-test at 

the 95% confidence interval. The t-tests indicated a significant difference in the UDMH 

concentration at each time interval from the Time 0 value. 

Some limitations of the study include: 1) no mention on storage conditions of sample extracts or 

on storage stability testing; 2) ambient temperatures during the storage duration, dates of sample 

collection, extraction and analysis were not reported, and 3) the sampling was not performed to 

simulate actual field conditions (e.g., temperature range, exposure to sunlight or no exposure to 

sunlight, possible agitation of tank mix, etc.). 

Page 18 of19 
.§. = 0.1525x + 0.0648 3.000 R2 = 0.998 

.::. "' 2.500 

1: 

6 2.000 

v 

::1: ::!!: 1.500 

c 

::I 

cu 1.000 

1111 

l! 

0.500 +---...,.f!C-----------------

< 

0 5 10 15 20 25 30 

Time Interval (hours) 

Page 19 of19 

·-Linear (Series1)