Page 1 of 20 **UNITED STA TES ENVIRONMENTA**  **L PROTECTION A GENCY**  WA SHINGTON, D.C. 20460

OFFICE OF CHEMICAL SAFETY AND

POLLUTION PREVENTION DATE: November 30 , 2011 **MEMORANDUM SUBJECT:**  Amicarbazone : Occupational and Residential Exposure Assessment for Proposed

Use s on Turf, Christmas Tree Farms, Non
- Crop Areas and on Conifers in Nurseries. PC Code: 114004 DP Barcode : D3 94924 Decision No.: 441345 Registration Nos.: 66330 - 46 Petition Nos: NA Regulatory Action: Section 3 Registration Assessment Type: Occupational/Residential Case No .: NA TXR No.: NA CAS Number: 129909 - 90 - 6 MRID: NA 40 CFR: 180.615 **FROM:** Zaida Figueroa , Industrial Hygienist

Risk Assessment Branch (RAB) II Health Effects Division (7509P) **THROUGH:** Richard A. Loranger, Ph.D., Branch Senior Scientist

Risk Assessment Branch (RAB) II Health Effects Division (7509P) **TO:** Michael Walsh/Kathry n Montague , RM Team 2 3 Herbicide Branch Registration Division (7505P) **A ction Requested**  : The Registration Division (RD) requested that the Health Effects Divis i on (HED) conduct an exposure and risk assessment for proposed uses of the herbicide amicarbazone to control broadleaf weeds in residential and commercial lawns, golf course, sod farms, recreational turf, non - crop areas, Christmas tree farms and c onifers in nurseries
. The proposed use pattern results in the first residential use for the active ingredient. Note: This memorandum was reviewed b y the Exposure Science Advisory Committee (Exp oSAC) on October 20 , 2011.Page 2 of 20

**1.0 E**  **xecutive Summary** Amicarbazone, 4
- amino
- 4,5 - dihydro
-N - (1,1
- dimethylethyl)
- 3 - (1
- methylethyl)
- 5 - oxo - 1H - 1,2,4 - triazole
- 1 - carboxamide, is a triazolinone herbicide related to carfentrazone, flucarbazone, propox ycarbazone, and sulfentrazone. A Section 3 registration of a dry flo wable formulation is requested b y Ary sta LifeScience North America, LLC for use on turf ( lawns, golf course, sod farms, recreational turf

) , ornamentals, non
- crop areas, Christmas tree farms and c onifers in nurseries . Application timing includ e s pre - emerge nce and early post - emergence to control broadleaf weeds
. Amicarbazone may be applied through a variety of application methods including ground equipment, backpack, and hand held equipment. This assessment addresses exposure and risk associated with the proposed end
- use product for amicarbazone when used as directed b y commercial applicators as well as residential homeowner s . There is a potential for short
- and intermediate
- term occupational exposure associ ated with handl er activities (mixing, loading, and appl yi ng) as well as with postapplication activities (i.e., re
- entering treated areas ) . There is also a potential for short
term residential exposure to amicarbazone during handling (mixing, loading, and appl yi ng), and postapplication activities. Chronic exposure is not expected for the proposed use patterns
. Hazard Characterizatio n The toxicology

database is complete and adequate for purposes of this risk assessment. Amicarbazone exhibits low acute tox icity
. The available database indicates that the major effects in mammals are general toxicity , as evidenced by decreased body weight and weight gain, and liver toxicity
. The mutagenicity battery for this chemical is complete and indicates that amicarbaz one is not a mutagen. Amicarbazone has been classified as “not likely to be a human carcinogen”. Although the acute neurotoxicity study in rats showed signs of neurotoxicity , no such effects were seen in the subchronic and developmental neurotoxicity stu dies. In the previous risk assessment for amicarbazone ( K. Kosick, 8/10/2005 , D288216 ), HED concluded there was no dermal endpoint based on the lack of sy stemic toxicity or local dermal irritation from a 21 - day

dermal toxicity

study in the rat
. Using a ratio of the L OAELs from several oral studies in the rat to the NOAEL from the 21
- day dermal rat study

(1000 mg/kg/day), a conservative dermal absorption factor of less than 5% was estimated. Therefore, dermal absorption is not considered to be a major route of uptake for this chemical and the dermal route of exposure was not considered for this risk assessment. Inthe absence of a route
- specific study for inhalation, HED selected an endpoint from the 90
- day dog study

for the inhalation exposure and risk assessment. The re were numerous effects observed at the LOAEL of 25 mg/kg/day ( thy roid, liver, gall bladder, and blood); the NOAELof 6. 2 8 mg/kg/day was selected as the point of departure for inhalation risk assessment. Since no inhalation toxicity data are available, toxicity by the inhalation route is considered to be equivalent to toxicity by the oral route of exposure. For the current risk assessment, HED selected an endpoint for the purpose of assessing children’s incidental oral exposure on tre ated turf. Only short
- term (1
- 30 day s) durations are relevant for this route of exposure. T he same subchronic oral toxicity study in the dog used for assessing inhalation exposure and risk was selected for assessing incidental oral exposure.Page 3 of 20

FQPA and Uncertainty

Factors The database is complete with respect to pre
- and post
- natal toxicity and shows no evidence of increased qualitative or quantitative susceptibility
. Although neurotoxicity was observed with exposure to amicarbazone in adult animals in gavage studies, no neurotoxic effects were observed in offspring at dose levels that resulted in general s ys temic toxicity . Potential immunotoxic effects were observed in the chronic dog and rat immunotoxicity studies onl y at doses greater than those sele cted for risk assessment and are therefore not of concern. HED recommends that the special 10X FQPA safety factor be reduced to 1X . No other database uncertainty factors are needed
. The combined uncertainty factors of 100X (10X for intraspecies variabil ity

and 10X for interspecies extrapolation) serve as the level of concern (LOC) for occupational and residential exposure and risk . M argins of exposure (MOEs) greater than 100 are not of concern. Residential Handler Exposure A dermal exposure assessment w as not performed for residential handlers because no dermal endpoints were selected. Inhalation MOEs for handlers were significantl y greater than the LOC of 100 (ranging from 3, 6 00 to 220,000 ) and are not of concern. Residential Postapplication Exposure In the absence of a dermal endpoint, o ral non
- dietary ingestion exposures were assessed for children (i.e. soil ingestion, and hand
- /object
- to - mouth). The postapplication scenarios resulting from commercial and residential applications were assessed usi ng the HED Draft Standard Operating Procedures (SOP’s) for Residential Exposure Assessments, 2000
. S hort
- term hand
- to mouth (HTM), object
- to - mouth (OTM) and soil ingestion scenarios resulted in MOEs ranging from 9 1 0 to 2 70,000 , and are not of concern. Since the proposed uses of amicarbazone are applied only in outdoor settings and amicarbazone has a low vapor pressure ( 2.3 x 10 - 8 mm Hg ) , postapplication residential inhalation exposure and risk e s timates were not quantitatively assessed. Summary of Residential Exposure HED combines risk values resulting from separate exposure scenarios when it is likely they can occur simultaneousl y based on the use pattern and the behavior associated with the exposed population. However, since a dermal endpoint was not selected, the onl y relevant route of exposure for adults is through the inhalation route. Therefore, an adult combined residential exposure assessment was not conducted. Similarly, the onl y relevant route of exposure for children was through the oral route , and therefore a combined residential exposure assessment was not conducted for children. Occupational Handler Exposure 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 the Pesticide Handlers Exposure Database Version 1.1 (PHED 1.1), the Agricultural Handler Exposure Task Force (AHETF) database, the Outdoor Residential Exposure Task Force (ORETF) database, or other registrant
- submitted occupational exposure studies. Some of thesePage 4 of 20

data are proprietary

(e.g., AHETF data, MRID No. 4433980 1), and subject to the data protection provisions of FIFRA. Default assumptions established by the Health Effects Division (HED) Science Advisory

Council for Exposure were used for parameters such as body weight, acres treated and amount handled. All occ upational handler scenarios resulted in MOEs greater than the level of concern at the baseline PPE level of protection (i.e. single layer clothing and no respirator)
. Occupational Postapplication Exposure In the absence of a dermal endpoint, a dermal pos tapplication exposure assessment was not conducted
. Furthermore, s ince the proposed uses of amicarbazone are in outdoor settings where postapplication inhalation exposures are expected to be minimal , and because amicarbazone has a low vapor pressure ( 2.3 x 10 - 8 mm Hg ) , handler inhalation exposure estimates are considered to be protective of occupational postapplication inhalation exposure scenarios. Restricted Entry

Interval The restricted entry

interval (REI) listed on proposed labels is based on the ac ute toxicity of the technical material. Amicarbazone exhibits low acute toxicity and is classified as Toxicity Category III for eye irritation and Category IV for acute dermal and dermal irritation . It is not a dermal sensitizer. Acute toxicity Category III and IV chemicals require a 12
- hour REI. Therefore , the 12
- hour REIwhich appears on the proposed labels is considered appropriate
. Review of Human Research This risk assessment relies in part on data from studies in which adult human subjects were intentionally

exposed to a pesticide or other chemical. These data, which include studies from the Pesticide Handlers Exposure Database Version 1.1 (PHED 1.1); the Agricultural Handler Exposure Task Force (AHE TF) database; and the Outdoor Residential Exposure Task Force (ORETF) database; are subject to ethics review pursuant to 40 CFR 26, have received that review, and are compliant with applicable ethics requirements. For certain studies that review may have included review by the Human Studies Review Board. Descriptions of data sources as well as guidance on their use can be found at http://www.epa.gov/pesticides/science/handler
e xposure - data.html and http://www.epa.gov/pesticides/science/post
- app - exposure - data.html
. Label Recommendations **The Registration Division (RD)**  **should ensure the final label does not include the potential**  **for application to Christmas trees using a mechanically pressurized hand gun**  . No other recommendations are needed based on HED’s residential exposure and risk assessment. **2.0. H**  **azard Characterization** Amicarbazone is a triazolinone herbicide which controls broadleaf weeds by selective inhibition of acetolactase s ynthase, an enzy me involved in photosy stem II in plants. The available database indicates that the major effects in mammals are general toxicity , as evidenced by decreased body weight and weight gain, and liver toxicity . Decreased body weight and weight gain were observed in studies with rats, mice and rabbits and were the most sensitive toxicologicalPage 5 of 20

endpoints observed in many o f the studies. In the chronic dog and subchronic rat and dog studies, liver effects were seen; including increased absolute and relative liver weights, slight liver hy pertrophy , dilation of sinusoids and increased liver enzy mes and cholesterol/trigl yc erides. **2.1 Hazard Profile**  The toxicology

database is complete and adequate for risk assessment. Amicarbazone exhibits low acute toxicity
. The available database indicates that the major effects in mammals are general toxicity , as evidenced by decreased body weight and weight gain , and liver toxicity
. The mutagenicity

battery for this chemical is complete and indicates that amicarbazone is not a mutagen. Amicarbazone has been classified as “not likely to be a human carcinogen”. Although the acute neurotoxicity

study in rats show ed signs of neurotoxicity , no such effects were seen in the subchronic and developmental neurotoxicity studies. No dermal endpoint was selected for risk assessment, based on the lack of sy stemic toxicity or local dermal irritation in a 21 - day dermal tox icity

study in the rat
. Using a ratio of the LOAELs from several oral studies in the rat to the NOAEL from the 21
- day dermal rat study

(1000 mg/kg/day), a conservative dermal absorption factor of less than 5% was estimated. Therefore, dermal absorption i s not considered to be a major route of exposure for this chemical and the dermal route of exposure was not considered for this risk assessment. There was no route
specific inhalation toxicity study available for endpoint selection. Therefore, f or short
- term (1
- 30 day s) and intermediate
- term (1
- 6 month s) inhalation risk assessment , the endpoint was selected from a dog subchronic oral toxicity study in which numerous toxic effects were observed at the LOAEL of 25 mg/kg/day . These effects included th yroid, liver, gall bladder and blood toxicity . The NOAELfor the study was 6. 2 8 mg/kg/day , which served as the point of departure for risk assessment. For extrapolation from oral to inhalation exposure, toxicity via the inhalation route was assumed to be equivalent to toxicity via the oral route. **2.2 FQ**  **PA and Uncertainty Factor Considerations** HED has recommended the 10x FQPA factor be reduced to 1x. No evidence of increased quantitative or qualitative susceptibility was observed in the rat and rabbit d evelopmental toxicity , rat reproductive toxicity or the rat developmental neurotoxicity studies. Although neurotoxicity

was observed with exposure to amicarbazone in adult animals in gavage studies, no neurotoxic effects were observed in offspring in the rat developmental neurotoxicity study at dose levels that resulted in general s ys temic toxicity (decreased offspring and maternal body weight). Potential immunotoxic effects (chronic dog and rat immunotoxicity studies) were observed onl y at doses greater than those selected for risk assessment purposes and are therefore not of concern. Given the completeness of the database, there are no database uncertainty factors to be retained during risk assessment, and therefore the level of concern (LOC) is a margin of exposure (MOE) of 100, based on the combined uncertainty factors of 100X (10X f or interspecies extrapolation and 10X for intraspecies variability). MOEs greater than the LOC of 100 are not of concern.Page 6 of 20

**Table 1**  **. Acute Toxicity Profile for Am icarbazone.**  **Guideline No.**  **Study Type MRID(s)**  **Results Tox Category**  870.1100 Ac ute oral
- Wistar rats 45121504 Males LD 50 > 2050 mg/kg Females LD 50 = 1015 mg/kg III

870.1200 Ac ute dermal
- Wistar rats 45121503 LD 50 > 5000 mg/kg IV 870.1300 Ac ute inhalation
- Wistar rats 45121506 LC 50 > 2.030 mg/L IV 70.2400 Ac ute eye irritation
- New

Zealand white rabbit 45121510 Eye irritation was present (including corneal opacity) at 24 hours, but had cleared by day 7. III

870.2500 Ac ute dermal irritation
- New

Zealand white rabbit 45121509 Primary irritation indices were 0 IV 870.2600 Skin sensitization
- Hartley

guinea pig 45121628 45121505 All scores during

induction and challenge periods were 0. Not a dermal sensitizer

**Table 2**  **. Summary of Toxicological Doses and Endpoints for**  **Am icarbazone**  **for Use in Hum an Health Risk**  **Assessments .**  **Exposure/ Scenario**  **Point of**

**Departure Uncertainty/FQPA** 

**Safety Factors Level of** 

**Concern for Risk**  **Assessment Study and Toxicological Effects**  Incidental Oral Short
- Term (1
- 30 days) NOAEL=

6.28 mg/kg/day UF A= 10 x

UF H = 10 x FQPA SF= 1 x Residential

LOC for MOE = 100 90 - Day

Oral Toxicity in Dogs LOAEL = 25 mg/kg/day based on increased thyroid vacuolization and decreased food consumption and glucose in females; increased platelets, phosphate, bile acids, absolute and relative liver weights, and lymphoid hyperplasia of the gall bladder in males; and decreased albumin and increased triglycerides, N
demethylase and O
- demethylase in both sexes. Dermal ( all duration s) No systemic toxicity was observed at the limit dose. E vidence of low dermal absorption was estimated by comparison of oral and dermal studies in the rat.Page 7 of 20

**Table 2**  **. Summary of Toxicological Doses and Endpoints for**  **Am icarbazone**  **for Use in Hum an Health Risk**  **Assessments .**  **Exposure/ Scenario**  **Point of**

**Departure Uncertainty/FQPA** 

**Safety Factors Level of** 

**Concern for Risk**  **Assessment Study and Toxicological Effects**  Inhalation Short
- and Intermediate
Term (1
- 30 days and 1
- 6 mo nths, respectively) NOAEL=

6.28 mg/kg/day (I nhalation toxicity considered equivalent to oral toxicity) UF A= 10 x

UF H = 10 x FQPA SF= 1 x Occupational/

Residential LOC for MOE = 100 90 - Day

Oral Toxicity in Dogs LOAEL = 25 mg/kg/day based on increased thyroid vacuolization and decreased food consumption and glucose in females; increased platelets, phosphate, bile acids, absolute and relative liver weights, and lymphoid hyperplasia of the gall bladder in males; and decreased albumin and increased triglycerides, N
demethylase and O
- demethylase in both sexes. Cancer (oral, dermal, inhalation) Classification: There was no treatment - related increase in tumor incidence when compared to

control. Dosing was considered adequate. This chemical is not likely to be a carcinogen. Point of Departure (POD) = A data point or an estimated point that is derived from observed dose
- response data and used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL = no observed adver se effect level. LOAEL = lowes t observed adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = potential variation in sensitivity among members of the human population (intraspecies). FQPA SF = FQPA Safety Factor. MOE = margi n of exposure. LOC = level of concern. **3.0 P**  **roposed Use Patterns** Amicarbazone, 4
- amino
- 4,5 - dihydro
-N - (1,1
- dimethylethyl)
- 3 - (1
- methylethyl)
- 5 - oxo - 1H - 1,2,4 - triazole
- 1 - carboxamide, is a triazolinone compound proposed for the control of annual broadleaf weeds. Amicarbazone selectively inhibits acetolactase sy

nthase, an enzy

me involved in photosy stem II of plants. Related compounds include carfentrazone, flucarbazone, propox ycarbazone, and sulfentrazone. Arysta L ifeSciences North America, LLC is current ly seeking use of amicarbazone for control of broadleaf weeds in turf ( i.e., lawns, sod farms, golf courses, recreational fields, etc), ornamentals, non - crop areas, Christmas tree farms and conifers in nurseries . Amicarbazone is formulated as a 70% dry fl owable powder. It is intended for pre
- emergence and post
- emergence applications. Broadcast a

pplications are to be made with ground equipment only ; spot treatments are to be made u s ing backpacks and hand held equipment
. The product is not to be applied b y aerial equipment or through irrigation s ys tems. Amicarbazone is available for use b y commercial and professional applicators
. This herbicide works best when applied and subsequentl y moved into the soil by rainfall
. The personal protective equipment (P PE) for the proposed label consists of baseline clothing (i.e., long
sleeved shirt and long pants , shoes and socks ) and use of chemical resistant gloves
. The proposed uses are anticipated to result in short
- and intermediate
- term exposure durations. Table 3 provides a summary

of the proposed uses.Page 8 of 20

**Table 3**  **. Proposed Products and Uses of Amicarbazone. Product**  **Trade Name**  **(EPA Reg. No.) Crops**  **Method of Application**  **Ma xim**  **um**

**Application Rate**  **s †**  **Ma x**  **imum**

**Seasonal Applic**  **ation Rate**  **s Ma** **x imum #** 

**Applic ations**  **per Season Use Directions and other** 

**Lim itations**  **‡**

**Am icarbazone**  **DF Herbicide (DINAMIC**  **70 WDG**  **HERBICIDE)** 70% ai (EPA Reg. No. 66330 - 46) Turf, golf course,

sod farms, parks and recreation areas, athletic fields, landscape plants and tree nurseries, and Christmas trees farms Directed; Broadcast using ground equipment only
. Spot treatment using backpack and compression sprayers. 0.4 6 lb ai/A

(single application) (10 .5 oz prod/A) (0.02 3 lb ai/gal) 0.4 6 lbs ai/

A/yr 1 appl at the

max appl. rate. 2 - 4 appls for turf grass at a lower rate. 12 - hr REI

Application intervals from 14 - 21 days, but may vary depending on application rate . Do not apply within 4 weeks of cutting or lifting sod. Do not apply this product using aerial equipment or any irrigation system. † Max Single Application Rate = ( 70% ai ) (1 lb solid /16 oz) (10 .5 oz/A) = 0.4 6 lb ai/A (1 A/20gal) = 0.02 3 lb ai/gal. ‡ Minimum Spray Volume = 20 gal/A. Note: T he proposed label states that the maximum single application rate for turf is 10 oz prod/A. However, f

or purposes of this assessment HED used the maximum single application rate of 10.5 oz prod/A based on information provided by the registrant ( MRID No. 48237522 )
. **4.0 R**  **esidential (N**  **on -**  **O ccupational** **) E xposure**  **4.1 Residential Handler Exposure and Risk**  The Agency

uses the term “Handlers” to describe those individuals who are involved in the pesticide application process. Based on the proposed label ( EPA Reg. No. 66330 - 46) and information provided b y the registrant (MRID No. 48237522 ), this product is to be applied by profession al applicators. The proposed label includes occupational/commercial mixing/loading activities , PPE and REI requirements
. However, s ince the proposed label does not identify this product as a restricted use pesticide , a residential handler exposure assessment was performed to be protective of potential homeowner exposure. The following exposure scenarios and unit exposures were used to assess residential handler s for broadcast and spot treatments:

 Mixing/L oading/Applying for Spray s with Backpack Sprayer;  Mixing/L oading/Applying for Spr ay s Using Low
- Pressure Handwand ; and,  Mixing/L oading/Applying for Spray s with Hand
- Gun Sprayer (hose
- end). **4.1.1 Data and Assumptions**  **Unit Exposures:** No chemical specific unit exposure data were provided in support of this submission; therefore, HED used data from the PHED Surrogate Exposure Guide for Residential Handlers, Version 1.1, August 1998 and the Occupational Residential Exposure Task Force (ORETF) (MRID 449722
- 01).Page 9 of 20

**Acres/Amount Treated** : In formati on regarding area treated for the various use scenarios was provided b y the Science Advisory Council for Exposure Policy #12: Recommended Revisions to the Standard Operating Procedures (SOPs) for Resid e ntial Exposure Assessments. **Exposure Duration:** Bas ed on information provided in the proposed labels, residential handler expos ure is anticipated to be short
- term in duration. **Body Weight:** The average adult body weight of 70 kilograms was used to assess handler exposure since the endpoint s w ere not gender specific
. **4.1.2 Residential Handler Exposure and Risk**  **Estimates** A quantitative dermal ass essment for residential handlers was not conducted since n o sy stemic toxicity by the dermal route was seen at the limit dose in the dermal toxicity study . Handler inhalation exposure scenarios resulted in MOEs greater than 100 and therefore are not of concern . Handler exposure and risk estim ates are summarized in **Table 4**  . **Table 4**  **. Residential Handler Exposure**  **Estimates for**  **Amicarbazone. Scenario**  **Inhalation Unit**

**Exposure a**  **(m g/lb ai)**  **Application Rate b**  **Am ount Treated**  **c Inhalation Dose**  **d (m**  **g/kg/day) Inhalation MOE**  **e Mix/Load/Apply**  Backp ack Sprayer (Ground Directed) 0.03 (Baseline) (PHED) 0.02 3

lb ai/gal 5 Gal 0.0000493 130,000
Lo w Pressure Handwand 1 . 063 (Baseline) (PHED) 5 Gal 0.00175 3,600 Hose - end (for Handgun Sprayer) (Mix your own) 0.01 7 (Baseline)

(ORETF
- OMA004 ) 0.023 lb ai/gal 5 Gal 0.000028 220,000 0.4 6 lb ai/A 0.5 A 0.000056 110,000

a. PHED Surrogate Exposure Guide for Residential Handlers , Version 1.1, August 1998
. Occupational Residential Exposure Task Force (ORETF) Study Data (MRID 449722
- 01)
. b. Application Rate = ( 70% ai ) (1 lb solid /16 oz) (10.5 oz/A) = 0.46 lb ai/A (1 A/20gal) = 0.023 lb ai/gal
. c. Policy 12: Recommended Revision to the SOPs for Residential Exposure Assessment
. d. Inhalation D ose (mg/kg/day) = I nhalation U nit E xposure (mg/lb ai) * A pplication Rate * A cres T reated or Amount Handled / B ody W eight (70 kg)
. e Inhalation MOE = NOAEL ( 6.28 mg/kg/day) / Inhalation Dose (mg/kg/day)
.Page 10 of 20

**4.2 Residential Postapplication Exposure**  Amicarbazone residential postapplication scenarios include children (3 to 6 years) playing on treated turf, adults performing yard work on treated turf and adults playing golf on treated turf. As a result, a wide array

of individuals of varying ages can potentially be exposed when they

do acti vities in areas that have been treated. The postapplication scenarios were assessed using the HED Draft Standard Operating Procedures (SOP’s) for Residential Exposure Assessments, 2000
. Since n o chemical
- specific residue data w ere submitted for this acti on, postapplication exposures were assessed using default assumptions from the Residential Exposure SOPs. **4.2.1 Inhalation Postapplication Exposure**  Based on the Agency's current practices, a quantitative postapplication inhalation exposure assessment was not performed for amicarbazone at this time primarily because of the low acute inhalation toxicity

(Toxicity Category IV) , the low vapor pressure ( 2 .3 x 10 - 8 mm Hg ) and the proposed application rate (0.46 lb ai/A)
. However, volatilization of pesticides may be a potential source of postapplication inhalation exposure to individuals nearb y to pesticide applications. The Agency

sought expert advice and input on issues related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on March 2, 2010 (http://www.epa.gov/scipoly /SAP/mee tings/2009/120109meeting.html ). The Agency is in the process of evaluating the SAP report and may , as appropriate, develop policies and procedures to identify the need for and, subsequently , the way to incorporate post
- application inhalation exposure into the Agency's risk assessments. If new policies or procedures are developed, the Agency may revisit the need for a quantitative pos
- application inhalation exposure assessment for amicarbazone. **4.2.2 Dermal Postapplication Exposure**  In assessing potential dermal postapplication exposure and risk estimates , HED assumes that pesticide residues are transferred to the skin of adults/ children who enter treated yards for recreation or other activities such as yard work and golf ing
. However, a quantitative p ostap plication dermal exposure assessment was not performed for adults and children since no dermal endpoints were selected
. I f dermal toxicological endpoints change in the future, HED may require a turf transferable residue (TTR) study to confirm that assessm ents are protective of all turf uses. **4.2.3 Non**  **- Dietary Ingestion**  **(Hand -**  **to -**  **Mouth) Exposure**  For the assessment of n on - dietary i ngestion (hand
- to - mouth ) exposure, HED assumes that pesticide residues are transferred to the skin of children playing on treated areas and are subsequently

ingested as a result of hand
- to - mouth transfer.Page 11 of 20

Assumptions:

 On the day

of application, it is assumed that 5% of the application rate is available on turf grass as transferable residue.  Oral postapplication exposure was estimated using the standard assumption for the initial fraction of residues available and assuming a 10% daily dissipation rate.  The median surface area of both hands is 20 cm 2 for children.  It is assumed that there is a one - to - one relationship between the dislodgeable residues on the turf and on the surface area of the skin after contact.  The mean rate of hand
- to - mouth activity is 20 times/hour for short
- term exposure scenarios.  The saliva extraction factor is 50%
.  The c hildren (3
- 6 y

rs) are assumed to weigh 15 kg
.  Duration of exposure for children is assumed to be 2 hours per day for turf
. Equations: **TTR t**  **= AR x F x (1 -**  **D) t**  **x CF2 x CF3** TTR = Turf Transferable Residue; AR = A pplication rate (lb ai/acre) ; F = Fra ction of ai available on turf (unitless) (0. 0 5) ; D = F raction of residue that dissipates daily (unitless) (0.1) ; t = P ostapplication day on which exposure is being assessed ; CF2 = W eight unit conversion factor to convert the lbs ai in the application rate to ug for DFR value (4.54 x 10 8 ug/lb) ; and, CF3 = Area unit conversion factor to co nvert the surface area units (acre ) in the application rate to cm2 for the DFR value (2.47 x 10 - 8 acre/cm 2 )
. **PDR = TTR x SA x FQ x ET x SE x CF1** 

**BW** PDR = P otential dose rate (mg/day) ; TTR = T urf transferable residue (ug/cm2 turf) ; S A = S urface area of the hands ( 20 cm 2 /event) ; FQ = F requency of hand
- to - mouth activity (20 events/hr for short
- term) ; ET = E xposure time (hr/day) ; CF1 = W eight unit conversion factor to convert ug units in the TTR value to mg for the daily exposure (0.001 mg/ug for turf) ; SE = Saliva Extraction Factor (50%) ; and, BW = Body Weight ( 15 kg ). **Hand -**  **to -**  **Mouth Exposure and Risk**  **Estimate** S hort
- term hand
- to - mouth (HTM) exposure resulted in an MOE greater than the level of concern (MOEs ≥ 100) and therefore pose s no risk of concern. **Table 5**  p rovides a summary of the short
term HTM exposure e s timate
.Page 12 of 20

**Table 5**  **. Am**  **icarbazone Children’s Short**  **- term**  **Non -**  **Dietary Ingestion (Hand**  **- to**  **- Mouth)**  **Exposure and Risk Estimate**  **. Product**  **TTR 1**  **(ug/cm 2**  **) SA** 

**(cm 2**  **/event )**  **FQ SE**  **ET (hr/day)**  **CF 1**  **BW**

**(kg) HTM Dose**  **2 (m**  **g/kg/day) HTM** 

**MOE 3**  Amicarbazone DF Herbicide (DINAMIC 70 WDG HERBICIDE) 70% ai (EPA Reg. No. 66330
- 46) 0.2576 20 20 0.5 2 0.001 15 0.00687 910

1. Turf Transferable Residues = (TTR) = AR (0. 4 6 lb ai/A) x F (0.05) x (1
- D) 0 x CF2 (4.54E 8 μg/lb) x CF3 (2.47E - 8 acre /cm2 ) = 0.2576 ug/cm2

. 2. HTM Dose = [ TTR t x SA x FQ x ET x SE x CF1 ]/BW . 3. HTM MOE = NOAEL ( 6.28 mg/kg/day)/HTM Dose (mg/kg/day)
. **4.2.4 Non**  **- Dietary Ingestion**  **( Object to Mouth Ingestion of Treated Turf)**  **Exposure** This scenario estimates exposure to children (3
- 6 y rs) resulting from incidental ingestion of pesticide and

/ or residential turf grass that has been treated with pesticides. It assumes that pesticide from a treated object or turf is ingested by children who play on treated areas. Assumptions:

 On the day

of application it is assumed that 20% of the application rate is available to be ingested.  Oral postapplication exposure was estimated using the standard assumption for the initial fraction of residues available and assuming a 10% daily dissipation rate.  Assumed ingestion rate for grass for children (3 years old) is 25 cm 2 /day
.  Children are assumed to weigh 15 kg. Equations: **GR t**  **= AR x F x (1 -**  **D) t**  **x CF2 x CF3** GR t = grass residue on day t (ug/cm2 ) ; AR = application rate (lb ai/A) ; F = fraction of ai available on the grass (unitless) (0.2) ; D = fraction of residue that dissipates daily (unitless) (0.1) ; t = postapplication day on which exposure is being assessed ; CF2 = weight unit conversion factor to convert the lbs ai in the application rate to μ g for grass residue value (4.54 x 10 8 μg/lb) ; and, CF3 = area unit conversion factor to convert surface area units (A) in the application rate to cm 2 for grass residue value (2.47 x 10 - 8 A/cm 2 )
. **PDD = GR t**  **x IgR x CF1** PDD = potential daily dose (mg/kg/day) ; GR t = grass residue (ug/cm2 ) ; IgR = ingestion rate of grass (cm2 /day) ; and,Page 13 of 20

CF1 = weight unit conversion factor to convert the μg of residues on the grass to mg to provide units of mg/day (1 .0 x 10 - 3 mg/μg )
. **Object -**  **To -**  **Mouth Exposure and R isk**  **Estimate** The object
- to - mouth (OTM) scenario resulted in an MOE greater than the level of concern (MOEs ≥ 100) and therefore poses no risk of concern. **Table 6**  provides a summary of the OTM exposure and risk estimate
. **Table 6**  **. Am**  **icarbazone Children’s Non**  **- Dietary Ingestion**  **( Object** 
**– to**  **- Mouth**  **) Exposure and**  **Risk Estimate**  **.**

**Product GR**  **1**

**(ug/cm 2**  **) CF**  **1**

**(m g/μg**  **) IgR** 

**(cm 2**  **/day) BW** 

**(kg) OTM Dose**  **2 (m**  **g/kg/day) OTM** 

**MOE 3**  **Am icarbazone DF Herbicide**  **(DINAMIC 70 WDG HERBICIDE)**  70% ai (EPA Reg. No. 66330 - 46) 1.03 0.001 25 15 0.0017 3,700

1. GR (grass residue) = Application Rate x F x (1
- D) 0 x CF2 x CF3 . 2. OTM Dose = [ GR 0 x IgR x CF1 ] /BW
. 3. OTM MOE = NOAEL ( 6.28 mg/kg/day)/OTM Dose (mg/kg/day)
. **4.2.5 Non**  **- Dietary Ingestion**  **Incidental Ingestion of Soil** This scenario assumes children who play on treated areas ingest pesticide residues in soil as a result of normal mouthing activities. Assumptions:

 On the day

of application, it is assumed that 100% of the application rate is located within the soil’s uppermost 1 cm.  Postapplication must be assessed on the same day the pesticide is applied.  Assumed soil ingestion rate for children is 100 mg/day
.  Childre n are assumed to weigh 15 kg. Equations: **SR 0**  **= AR x F x (1 -**  **D) t**  **x CF2 x CF3 x CF4** SR0 = soil residue on day 0 (ug/g) ; AR = application rate (lb ai/A) ; F = fraction of ai available in uppermost cm of soil (1 cm) ; D = fraction of residue that dissipates da ily (unitless) ; t = postapplication day on which exposure is being assessed (day 0) ; CF2 = weight unit conversion factor to convert the lbs a i in the application rate for soil residue value (4.54 x 10 8 μg/lb) ; CF 3 = area unit conversion factor to convert surface area units (A) in the application rate to cm 2 for soil residue value (2.47 x 10 - 8 A/cm2 ) ; and, CF4 = volume to weight unit conversion factor to convert the volume units (cm3 ) to weight unitsPage 14 of 20 for th e SR value (0.67 cm3 /g soil)
. **PDD = SR 0**  **x IgR x CF1** PDD = potential daily dose on day 0 ; SR0 = soil residue on day 0 (ug/g) ; IgR = ingestion rate of soil (mg/day) ; and, CF1 = weight unit conversion factor to convert the μg of residues on the soil to mg to provide units of mg/day (1 .0 x 10 - 6 g/μg)
. **Soil Ingestion Exposure and Risk Estimate**  The soil
- ingestion scenario resulted in a MOE much greater than the level of concern (MOEs ≥ 100) and therefore poses no risk of concern. This assessment should be considered conservative in that it assumed no dissipation of soil residues would occur over the exposure period. **Table 7**  provides a summary

of the soil ingestion exposure and risk estimate
. **Table 7**  **. Am**  **icarbazone Children’s Soil Ingestion Exposure and Risk**  **Estimate .** 

**Product SR**  **1**

**(ug/g) CF**  **1**

**(g/μg )**  **IgR**

**(m g/day)**  **BW**

**(kg) Dose**  **2 (m**  **g/kg/day) MOE**  **3 Am** **icarbazone DF Herbicide (DINAMIC 70 WDG**  **HERBICIDE)** 70% ai (EPA Reg. No. 66330 - 46) 3.45 0.000001 100 15 0.000023 270,000

1. SR0 (soil residue) = Application Rate (lb ai/A) x F(1) x (1
- D) 0 x 0.67 x (4.54x10 8 μ g/lb )x (2.47 x 10 - 8 A/cm2 )
. 2. Soil Ingestion Dose (mg/kg/day) = SR0 (μg/g) x IgR (mg/day) x CF1 (g/μg)/BW (kg)
. 3. Soil Ingestion MOE = NOAEL ( 6.28 mg/kg/day)/Soil Ingestion Dose (mg/kg/day)
. **4.3 Summary of**  **Residential Risk Estimates** HED combines risk values resulting from separate exposure scenarios when it is likely they can occur simultaneousl y based on the use pattern and the behavior associated with the exposed population. In evaluating combined residential uses of amicarbazone , HED reviewed all residential sources of exposure which consisted of : 1) adult inhalation handler (lawns onl y) exposure, and 2) child postapplication oral exposure. Since a dermal endpoint was not selected for amicarbazone, the onl y relevant route of exp osure for adults is through the inhalation route, and therefore, a combined residential exposure assessment is not applicable
. The children’s oral exposure estimate for the purpose of conducting an aggregate risk assessment is based on postapplication h and
- to - mouth exposures only
. To include exposure from object
- to mouth and soil ingestion in addition to hand
- to - mouth could result in a very conservative estimat e of exposure since the assumptions for each of the individual oral exposure calculations are high end
.Page 15 of 20

The hand
- to - mouth residential postapplication scenario also represents the worst case of oral exposure (i.e., t o include exposure from object
- to - mouth and soil ingestion in addition to hand
to - mouth could result in a very conservative estimation of exposure as it would overestimate the potential of oral exposure )
. **Table 8** identifies the residential scenarios and MOEs for adults and children for use in performing an aggregate exposure assessment as part of the amicarbazone human health risk assessment. There are no risks of concern.
**Table 8**  **. Am**  **icarbazone Summary of Residential Exposure and Risk**  **Esti ma**  **tes .**  **Product Use Site**  **Handler Inhalation**  **MOE 1**  **Postapplication**

**Derm al MOE**  **Hand -**  **to -**  **Mouth**

**MOE 2**  **Combined**

**MOE 3**  **Adult Am** **icarbazone DF Herbicide (DINAMIC**  **70 WDG HERBICIDE**  (EPA Reg. No. 66330
- 46) Lawns (turf) 3, 6 00 NA NA NA
**Child Am** **icarbazone DF Herbicide (DINAMIC**  **70 WDG HERBICIDE)** (EPA Reg. No. 66330
- 46) Lawns (turf) NA NA 910 NA
1. See Table 4 : Residential Handler Exposure and Risk ( Low Pressure Handwand)
. 2. See Table 5 . Hand
- To - Mouth Exposure and Risk
. 3. Child MOE = NOAE L ( 6.28 mg/kg/day)/HTM D ose ( 0.00 687 mg/kg/day)
. **4.4 Spray Drift**  Spray drift is alway s 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 metho d employed for amicarbazone
. 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 information at http://www.epa.gov/opp00001/factsheets/spraydrift.htm). On a chemical by chemical basis, the Agency is now requiring interim mitigation measures for aerial applications that must be placed on product labels/labeling. The Agency has completed its evaluation of the new database submitted by

the Spray

Drift Task Force, a membership of U.S. pesticide registrants, and is developing a policy

on how to appropriatel y apply the data and the AgDRIFT computer model to its risk a ssessments for pesticides applied b y air, orchard airblast and ground hydraulic methods. After the policy

is in place, the Agency

may impose further refinements in spray drift management practices to reduce off
- target drift with specific products with significant risks associated with drift. It is noted that the 0.46 lb ai/acre application rate for turf was modeled to estimate postapplication residential exposure of children . As this rate is the same as the maximum agricultural single application rates ( 0.46 lb ai/A) , this scenario is protective of any exposure of farm children via spray

drift from agricultural applications of amicarbazone
.Page 16 of 20

**5.0 O**  **ccupational Exposure** Amicarbazone DF Herbicide (Alternate Brand Name: DINAMIC 70 WDG Herbicide) , is a dry flowable (water - dispersible granular) formulation for the control of weeds in turfgrass, including golf courses (i.e., fairways, roughs, tees and approaches), seed production, sod production, and residential and commercial sites (i.e., homes, schools, playgrounds, parks, recreational areas, sports fields and common areas) as well as in tree sites (i.e., tree nurseries and Christmas tree farms). This product will be applied as a spray after mixing with water or a liquid fertilizer. Based on information pro vided by the registrant, th is product is intended to be applied onl y b y professional applicators (MRID No. 48237522 )
. Therefore, the potential for occupational handler and postapplication exposure does exist. **5.1 Occupational Handlers**  Based upon the pro posed use pattern, HED expects the most highly exposed occupational pesticide handler s cenarios to be : 1) mixing/loading dry

flowable for ground applications ; 2) applying spray s via open cab groundboom equipment ; 3) mixi ng/loading/appl yi ng liquids with manually pressurized ( low
- pressure ) handwand ; and, 4) mixing/loading/appl yi ng l iquids with a backpack sprayer . Handler exposure is expected to be short
- or intermediate
- term in duration based on information provided on proposed labels. Lo ng - term exposures are not e xpected; therefore, a long
- term assessment was not conducted. Unit Exposures 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 the Pesticide Handlers Exposure Database Version 1.1 (PHED 1.1), the Agricultural Handler Exposure Task Force (AHETF) database, and the Outdoor Residential Exposure Task Force (ORETF) database
. Some of these data are proprietary (e.g., AHET F data , MRID No. 44339801 ), 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 Pesti cide Handler Unit Exposure Surrogate Reference Table” (http://www.epa.gov/opp00001/science/handler
- exposure - table.pdf ), which, along with additional information on HED policy on use of surrogate data, including descriptions of the various sources, can be found at http://www.epa.gov/pesticides/ science/handler
- exposure data.html
. For pesticide handlers, it is HED standard practice to present estimates of dermal exposure for “baseline”, that is, for workers wearing a single layer of work clothing consisting of a long sleeved shirt, long pants, sh oes plus socks and no protective gloves, as well as for “baseline” and the use of protective gloves or other Personal Protective Equipment (PPE) might be necessary toPage 17 of 20

achieve a MOE greater than the LOC. The proposed product label involved in this assessment directs applicators and other handlers to wear long sleeved shirt and long pants, shoes plus socks, and chemical
- resistant gloves. Body Weight: The standard body

weight for the general population (70 kg) was used for all exposure scenarios covered in this risk assessment. Dermal Absorption: Although a dermal absorption rate of 5% was calculated for amicarbazone, HED has concluded that a dermal risk assessment is not needed. Exposure Frequency : No data on the number of exposure day s per ye ar was provided
. For this risk assessment, it was assumed that handlers would be exposed for less than 6 months per year (i.e. short
- /intermediate
term duration s ). Equations: Daily handler exposures are estimated for each applicable handler task with the ap plication rate, the area treated in a day , and the applicable dermal and /or inhalation unit exposure using the following formula: **Daily Exposure (mg ai/day) =** Unit Exposure (mg ai/lb ai handled) x Application Rate (lbs ai/Acre ) x Daily Area Treated (area/day) Where: Daily Exposure = Amount (mg or μg ai/day) inhaled that is available for inhalation absorption or amount absorbed that is available for dermal absorption ; Unit Exposure = Unit exposure value (mg or μg ai/lb ai) derived from OPHED ; Application Rate = Normalized application rate based on a logical unit treatment, such as acres, square feet, or gallons. Maximum values are generally used (lb ai/A, lb ai/sq ft, lb ai/gal); D aily Area Treated = Normalized application area based on a logical unit treatment such as acres (A/day), square feet (sq ft/day), gallons per day (gal/day) ; and, The daily dose is calculated by

normalizing the daily

exposure by

body weight and adjusting, if necessary , with an appropriate dermal and/ or inhalation absorption factor using the following formula: **Average Daily Dose (mg/kg/day) = [Daily Exposure (mg ai** **/day) x Absorption Factor**  **] / Body Weight (kg)**  **)** Where:Page 18 of 20 Average Daily Dose = Absorbed dose received from exposure to a pesticide in a given scenario (mg pesticide active ingredient/kg body weight/day); Daily Exposure = Amount (mg ai/day) inhaled/abso rbed that is available for inhalation /dermal absorption; Absorption Factor = A measure of the amount of chemical that crosses a biological boundary such as the lungs /skin ; and Body Weight = Body w eight determined to represent the population of interest in a risk assessment (70 kg for amicarbazone ). Risks for each applicable handler scenario are calculated using a MOE, which is a ratio of the NOAEL or LOAEL to the daily dose. In the case of amicarbazone , a NOAELwas used in the calculation. All MOE values were calculated using the formula below: **MOE= NOAEL (mg/kg/day) / Daily Dose (mg/kg/day) Occupational Handler Exposure and Risk**  **Estimates Table**  **9** presents the estimated short
- and intermediate
- term inhalation risks for workers
. All occupational handler scenarios resulted in MOEs greater than the level of concern at the baseline PPE level of protection (i.e. single layer clothing and no respirator)
. The MOEs shown in the table are all significantly

higher than HED’s level of concern of an MOE of 100, with the lowest MOE of 1 , 300 identified for handlers conducting mixing/loading activities for application to sod farms. **Based on communication with the registrant, t he proposed label will prohibit the use of a**  **mechanically pressurized handgun for application to Christmas trees.**Page 19 of 20

**Table 9**  **. Occupational Handler Exposures and Risks Estimates**  **for Amicarbazone. Exposure**  **Scenario and Product**  **Crops Application**  **Rate a**  **Area Treated or** 

**Am ount Treated**  **Inhalation Unit Exposure**  **b (m**  **g/lb) Inhalation Dose**  **c (m**  **g/k g/day)**  **Inhalation MOE d**  **Mi xer/Loader**  Ground

– Dry Flowable Golf courses 0.4 6 lb ai/A 40 A 0.00896 (Baseline) (AHETF) 0.00235 2,700 Sod farms (turf) , Christmas tre e s 80 A 0.00471 1,300 **Applicator** Open Cab Groundboom Golf courses 0.4 6 lb ai/A 40 A 0.00034 (Baseline) (AHETF) 0.0000894 70,000 Sod farms (turf), Christmas tre e s 80 A 0.000178 35,000 **Mi xer/** **L oader/Applicator**  Backpack Sprayer Christmas trees

(Ground
- Directed) 0.023 lb ai/gal 5 gals 0.00258 (Baseline) (MRID 44339801) 0.0000042 1,500,000 Turf, golf course, sod farms, parks, recreation and athletic fields Manually
pressurized Handwand Turf, Christmas trees 0.023 lb ai/gal 5 gals 0.03 (Baseline) (PHED) 0.000049 130,000 Mechanically
pressurized Handgun Sprayer (WDG) Turf, g olf courses

( Broadcast) 0.46 lb ai/A 5 A 0.042 (Baseline) (ORETF) 0.00138 4,500

a. Application Rate = ( 70% ai ) (1 lb solid /16 oz) (10.5 oz/A) = 0.46 lb ai/A (1 A/20gal) = 0.023 lb ai/gal. b. Occupational Pesticide Handler Unit Exposure Surrogate Reference Table ( September 2 6 , 2011). c. Inhalation Dose (mg/kg/day) = Inhalation Unit Exposure (mg/lb ai) * Application Rate * Acres Treated or Amount Handled / Body Weight (70 kg). d. Inhalation MOE = NOAEL ( 6.28 mg/kg/day) / Inhalation Dose (mg/kg/day)
.Page 20 of 20

**5.2 Occupational/Commercial**  **Postapplication Exposure 5.2.1**  **Postapplicati o**  **n Inhalation Exposure** Based on the Agency's current practices, a quantitative postapplication inhalation exposure assessment was not performed for amicarbazone at this time primarily because it has a low vapor pressure ( 2.3 x 10 - 8 mm Hg ) , it is applied at a maximum single application rate of 0.46 lb ai/A and it is not projected to be applied via typicall y high inhalation exposure application equipment (e.g., airblast and aerial equipment). However, volatilization of pesticides may be a potential source of postapplication i nhalation exposure to individuals nearb y to pesticide applications. The Agency

sought expert advice and input on issues related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009. The Agency received the SAP’s final report on March 2, 2010 (http://www.epa.gov/scipoly /SAP/meetings/2009/120109meeting.html ). The Agency is in the process of evaluating the SAP report and may , as appropriate, develop policies and procedures to identify the need for and, subsequently , the way to incorporate postapplication inhalation exposure into the Agency's risk assessments. If new policies or procedures are put into place, the Agency may revisit the need for a quantitative postapplication inhalation exposure assessment for amicarbazone
. Although a quantitative occupational postapplication inhalation exposure assessment was not performed, an inhalation exposure assessment was performed for occupational/commercial handlers. Handler exp osure resulting from application of pesticides outdoors is likely to result in higher exposure than postapplication exposure. Therefore, it is expected that these handler inhalation exposure estimates would be protective of occupational postapplication inhalation exposure scenarios. **5.2.2 Postapplication Dermal Exposure**  Postapplication exposure assessments were not performed because no dermal endpoints were selected. Restricted Entry

Interval The restricted entry

interval (REI) listed on proposed labels is based on the acute toxicity of the technical material. Amicarbazone exhibits low acute toxicity and is classified as Toxicity Category III for eye irritation and Category IV for acute dermal and dermal irritation. It is not a dermal sensitizer. Acute toxicity Category III and IV chemicals require a 12
- hour REI. Therefore, the 12
- hour REIwhich appears on the proposed labels is considered appropriate.