U N ITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON , D

. C

. 20460

Date: October 29, 2013 OFFICE OF CH EM I C A L SAFE TY AND POLLUT I ON PREVENT I ON

SUB J ECT: Gl u fosi n a t e A m mo niu m. Respo nse to Comme n ts on the Hu m an Hea lth Risk Asses s ment for Registrat io n Rev i ew. PC Cod e : 128850 Dec ision No. : 48360 1 Petition No .: NA DP Ba r co d e: D4 1 5395 Reg istra t io n N o. : NA Regu l atory Acti o n : Reg i stration Rev ie w Case No.: NA Ri sk Assess m ent Type: R esponse to Comments TXRNo .: NA MRIDNo .: NA CAS No.: 77182-8 2-2 4 0 CFR: 

### § 180.47 3
FROM :

# WilliamH.Donovan,Ph.D,Chem~·s i sF As

# LJ~CfJ**~~** John L iccione , Ph.D., Toxicologist An a Ri ve ra-Lup iafiez , Chemist · Ri sk Assess ment Branch V Health Effe cts D ivis ion (HED) (7509P) Office ofPesti c i de Programs (O PP) THROUGH: Michae l S
. Metzge r, Branch Chi e#/ /} 

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# ~ Ri sk Assessment Branch V Nil 

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# V HED/OPP (75 0 9 P) TO: Kat ie Weyrau ch, C he mi cal Review Manager Risk Manage m ent an d Impl em e n tation Branch 1 Pe s ticide Re-Evaluatio n D ivision (7508P) Bay er CropScience ( BCS) has submitted comments on the HED documents titled Glufosinate Ammonium
. Human Health Ris k Assessment for Registr a tion R eview (1/24113; D406360) , and Human H ealth RiskAssessmentfor the Propo sed New Use ofG/ufos inate Ammonium ini on Cit rus Fruit ( Crop Group 10) , Pome Fruit (Crop Group 11), Stone Fruit (Crop Group 12 ) , Olives and Sweet Corn ( 7/ 25 / 12; D387413 )
. In the prese nt memo , eac h i ss ue is briefly iden tifi ed , fo ll owed by BCS 's comments (fro m their su bmi ss i on dated 6/ 13 / 13 , Bayer CropScience Com m ents to EPA ' s draft Human Health and Ecological Risk assessments for the Regist ration Review ofGlufosinate Ammonium , Federal Reg i ster No ti ce 20 13-03-06 , Vol. 78, No .44,· Pes ticid e Docket Id e ntification No. EPA-HQ

- OPP- 2008-0 190; No MRID No
. ), and the current HED response . P age 1 of 8Detailed Considerations 1) Submission of new in vitro rat/human dermal absorption study. BCS: BCS requests that the Agency incorporate the results of the new in vitro rat/human dermal absorption study (Kane, 2009) into the glufosinate ammonium risk assessment. This may result in a s i gnificant rev i sion to the non-dietary exposure assessment. HED: The Agency has rev i ewed the in vitro rat/human dennal penetration studies (MRIDs 49135807; 49135805

- Kane 2009 studies) and in vivo rat dermal absorption study (MRID 49135806) that were submitted by BCS
. Of particular interest is whether or not the in vitro penetration and in vivo studies ("triple pack") can be used collectively to refine the human dermal risk assessment. To address the utility of the "trip l e pack'' for refinement of the dermal risk assessment, the Agency reviewed the studies based on OPP guidance on estimating dermal absorption factors for use in human health risk assessments. A cri tical criterion of the OPP guidance on using the "trip l e pack" is that identical protocols and test material and doses (in mass per unit area) are used in all three studies
. Based on information in the submitted studies, it appears that different formulations were used in the studies, i.e., SL 150 in MRID 49135805; SL 200 in MRID 49135807; and SL 14 in MRID 49135806. In add it i on, the concentrations of test substance were different among the three studies, with th e concentrations in the in vitro study limited to one low concentration and one very high concentration
. Another difference between the studies is that the in vitro studies included tape stripping whereas the in vivo study did not. The OPP guidance also considers the in vitro rat studies to be predictive of the rat in vivo study provided that the ratio of dermal absorption factors in the rat in vitro and in vivo studies ::::: 1
. F or glufosinate, the rati o was 0.2 when considering the low dose (3.21 1-ig / cm\ which is pertinent for human risk assessment (MRID 49135805). The Agency also notes that the differences between human and rat dermal absorption reported in the in vitro studies (i.e. , as high as 40-fold d i fferent) are considerably higher than what has been typically encountered with other chemicals using the "triple pack" approach. The reason for this discrepancy is not clear. In summary, based on OPP guidance, the Agency concludes that the "triple pack" cannot be utilized to further refine human dermal risk assessments. 2) Requirement for Dislodgeable Foliar Residue (DFR) studies for corn, canola, cotton, and soybean. BCS: The requirement to conduct DFR studies will be addressed once the results of the in vitro dermal absorption study (Kane, 2009) is considered and upon resolution of the 12 December 2012 DFR/TTR waiver policy. HED : The Agency has determined that the in vitro dermal absorption study (Kane , 2009) does not result in any changes to the glufosinate ammonium risk assessment. The requirements for DFR studies for corn, canola, cotton, and soybean identified in D406360 were based on criteria Page 2 of8given in a 617/12 Exposure Science Advisory Council guidance document. This guidance was included and finalized in the 12112/12 waiver policy memo noted by BCS
. Thus, according to the 12/12/2012 DFR/TTR waiver policy, the specified DFR studies are required for glufosi nate ammon ium since the post-application dermal MOEs are lowe r than 4000 (i.e. 4 X LOC) on Day 0 (scouting and/o r irrigation mature/high fo li age plants) based on default values for the fraction of application rate available for transfer after a foliar application. Therefore, the DFR studies for corn, canola, cotton, and soybean remain outstanding and shou ld be submitted. 

### 3) Crop use pattern information should include maximum single and seasonal use rates, re-trreatment intervals (RTis) and pre-harvest intervals (PHis). BCS: The most recent approved (09/27/2012) labels for Liberty® 280 SL Herbicide (EPA Reg. No. 264-829) and Liberty® 200 SL Herbicide (EPA Reg. No. 264-660) have been re vised to include maximum single and seasonal use rates, re - treatment intervals (RTis) and pre-harvest intervals (PHis). Bayer is willing to add the missing information (mainly re-treatment interval) to the Finale® Herbicide (EPA Reg. No. 4 32-1229), Derringer Herbicide (432-1228) and Derringer F Herbicide (432-960) whenever the Agency deems i t necessary. HED: This issue w i ll be resolved once the missing information is added to the Finale® Herbicide (EPA Reg. No. 432-1229), Derringer Herb icide (432-1228) and Derringer F Herbicide (432 -960 ) labels. 

### 4) Incorrect EPA Registration Number in Table 3.3 (page 9) of D387413. BCS: Please revise the registration number of the 2.34 lb/g al gl u fos i nate ammonium formulation to reflect the correct registration number 264-829. HED: HED concurs with this correction. 

### 5) Plant-Back Intervals (PBis) for rotational crops. BCS: The currently approved l abels for Liberty 280 SL Herbicide (EPA Reg. No. 264-829) and Liberty 200 SL Herbicide (EPA Reg. No. 264-660) lists the PBis for Root and Tuber vegetables, Leafy Vegetables, B r assica Leafy Vegetables and Small Grains (barley, buckwheat , oats, rye , teosinte, triticale, and wheat) as 70 days. The PBis for all other crops are 180 days. Canola, Swee t Corn, Corn , Cotton, Rice, Soybeans and Sugar beets may be planted back at any time. HED: HED concurs with th e rotational crop PBis specified by BCS. 

### 6) Exposure assessment for glufosinate ammonium broadcast application to dormant bermudagrass (golf course uses, residential lawn homeowner use). BCS: Exposure assessments for broadcast app li cation to dormant Bermudagrass should be included in the glufosinate ammonium risk assessment. BCS analysis shows acceptable risk levels for this use pattern.
Page 3 of8HED: HED concurs that an exposure assessmen t for use on dorm ant bermudagrass shou l d be included i n the g lufosinate ammonium ri s k assessment. Although this use pattern re sults in risks below HED's level of concern when considered by itself, i nclusion of this use pattern in the aggregate risk assessmen t results 

### in risk estimates that exceed H ED's l evel of concern unless the maximum use rate is reduced to 1.25 lb ai/A or less. The tex t below p rovides the details involved in reaching these conclusions. 

### Residential (non

- occupational) Exposure According to the 2012 HED's Residential SOPs (L awns/Turf section) the quantitative exposure/risk assessment developed for residential handlers is based on the follow i ng exposure scena rio:

• Mixing/loading/applying li quids wi th a hose-end sprayer, Res id ent i al Handler Exposure Data and Assumptions Short-term dermal and inhalation exposures were assessed fo r residential h andlers. A series o f assumptions and exposure fac tors served as the basis for completing the residential handler risk assessments . Each assumption and factor is detailed below. Application Rate A maximum single app li cation rate of 1.5 lb ai/ acre (6 quarts/acre) was used for the broadcast treatme n t scenarios to residential tu rf( EPA Reg. No. 432 -1 229). Unit Exposures andArea / Amount Treated Uni t exposure (UE) values and estima tes for area treated were taken from HED's 2012 Residential SOPs: Lawn s/Turf. Note: the Reg is trant's assessment did not use the correct UE values for this scenario. Body Weight The average female adult body weight of 69 kg was used for estimating short-term dermal dose because the selected toxicological POD is based on developmental effects; the average male adult body weigh t of 80 kg was used for estimating short-term inhalation dose. Absorption Factors A dermal absorption factor of 9% was used for the exposure assessment, based on a dermal penetrat i on study (D289836, B. Daiss , 17-JUN

- 2003). Fo r inh al ation risk assessment, a route specific study was used
. Exposure Duration Residential handler exposure is expected to be short-term. Intermediate- te rm exposures are not li kely because of the i ntermittent nature of applications by homeowners
. Endpoint Selection The endpoint to assess short-term dermal risk was brain morphometri c changes i n the developmen tal neurotoxicity study in r ats. Th e endpoint to assess short- term inhalation exposure
Page 4 of8was lung/bronch i al congest i on and increased lung/bronchi weight in females, and inc r eased kidney and liver we i ghts in a 28-day inhalation st u dy in rats. Residential Handler Exposure and R i sk Estimate Equations The algorithms used to estima te exposure and dose for residential handlers can be found in the 2012 Residential SOPs'. Summary of Residential Handler Non-Cancer Exposure and Risk Es ti mates I n th i s assessment, since the Points of Departure (PODs) selected for dermal and inhalation routes of exposure are based on d iffe r ent endpo i nts; the MOEs for th e dermal and inhalation exposure routes were not combined. Please note that B CS inco rrectly used an Aggregate R i sk Index (ARI) approach to assess risk. Short

- term exposures and risk estimates for residential handle r s perfo rming broadcast treatments on bermudag r ass do not exceed HED's leve l of concern (i.e., MOEs 

### 2: 1000 for dermal exposures and MOEs 2:300 for inhalation exposures). A Summary ofthe short-term dermal and inhalation risk estimates for residential hand l ers is i ncluded in Tab l e 1. Updated residenti al exposure ris k estimates are also provided for consideration in the aggregate risk assessment and presented on Table 2.
fr able 1. Residential Handler Non-cancer Exposure and Risk Estimates for Application of GlufosinateAmmonium on Residential Turf. Dermal Inhalation Area Treated Dermal Inhalation Ex p osure Unit Unit Maximum or Amount MOE4 MOE6 Scenari o Exposure Exposure Application Handled Dose Dose (m g/lb ai) (mg/lb ai) Rate 1 Daill (mg/kg/day) 3 (mg/kg/ da y ) 5 LO C =tOOO LO C= 300 Mixer/Loader / Applicator Hose-end Sprayer (Broadcast 13.4 0.022 1.5 lb ai/ acre 0
. 5 acres 0.013 1,100 0.00021 61,000 treatments ) I Based on reg1stered label ( EPA Reg. No. 432-1229). 2 Based on HED's 2012 Residential SOPs (http: / / www.epa . gov/ pes ticides/s cience / residen t ial-exposure-sop.html)
. 3 Dermal Dose = Dermal Unit Exposure (mg/lb ai) x Application Rate (lb ai/ acre or gal) x Area Treated or Amount Handled

(Alday or gallons/ day) x Derm a l Ab s orp t ion Factor (9%) .;. Body Weight (69kg)
. 4 Dermal MOE = Dermal NOAEL ( 14 mg/kg/day) + Dermal Dose (mglkg/day). 5 Inhalation Do s e = Inhalation Unit Exposure (mg/lb ai) x Application Rate (lb ai/ acre or gal) x Area Treated or Amount

Handled (Alday or gallon s/ day) + BW (80 kg)
. 6 Inhalation MO E= Inhal a tion NOAEL (12.5 mg/kg/day) + Inhalation Dose (mg/kg/day). Residential Post-Application Exposure Exposure is poss ible during post-application activities on treated turf. Children may experience exposure via incidental non-dietary ingestion (i.e
. , hand-to-mouth, objec t-to-mouth (turfgrass), and soil ingestion) during post-applicat i on activities on treated turf. Based on the Agency's current practices, post-applicati on dennal assessments are not performed for spot treatment u ses (HED's SOPs: Lawns/Turf; January 2012)
. These types of uses can result in residues on turf but residential exposure is expected to be low. Post app lication dermal exposure resulting from br oadcast treatmen ts to dormant bermudagrass was no t quantified for homeowners or golfers because of the unique use pattern of glufosinate

1 Availab le: http: //www . epa . gov/ pes ticides/ science / residential-exposure-sop.html

Page 5 of8ammonium
. The herbicide is app li ed to dormant bermudagrass during the winter when the weather is generally cold and winter clothing i s worn; therefore, post-application contact is li kely to be less. Other activities such as mowing the grass are either unlikely or not going to occur during this period. Bermudagrass remains dormant only when the temperatures during at least part of the day are consistently below freezing. The grass will begin to leave dormancy when there are several consecutive days where the temperature remains above freezing for multiple days. Therefore, post application exposure to glufosinate ammonium residues on dormant bermudagrass is expected to be negligib l e. Likewise, post-application inhalation exposure wh il e engaged in activities on or around previously treated turf is generally not assessed. The combination of low vapor pressure for chemicals typicall y used as active ingredients in outdoor residential pesticide products and dilution in outdoor air is likely to result in minimal inhalation exposure. Therefore, a quantitative post
- applicati on inhalati on exposure assessment was not performed for glufosinate ammon i um at this time primarily because it has very low vapor pressure (2
. 3 x 10

- 7 mmHg at 25°C). However, volatilization of pestic id es may be a potential source of post-application inhalation exposure to indiv idu als nearby 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 Scient i fic Advisory Panel (SAP) in December 2009. The Agency received the SAP's final report on March 2, 2010 (http: //www .e pa . gov/ sc ipol v / SAP / meet ings/ 200911 20 1 09mee tin g .html) and is in the process of evaluating the SAP report. The Agency may, as appropriate, develop policies and procedures to identify the need for and, subsequently, the way to incorporate post-app li cation inhalation exposure into the Agency's risk assessments. If new po li cies or procedures are put into place , the Agency may revisit the need for a quantitative post-application inhalation exposure assessment for glufosinate ammonium. However, it shoul d be noted that residential handler i nhal ati on exposures do not result in risks of concern (i
. e. M0£= 61,000)
. 

### Residential Risk Estimates for Use in Aggregate Assessment Table 2 reflects the residential risk estimates that are recommended for use in the aggregate assessment for glufosinate ammonium. • The recommended residential exposure for use in the adult aggregate assessment reflects dermal and inhalation exposure from broadcast applications to turf via hose-end sprayer.

Page 6 of8Label Recommendation A risk m i tigatio n option would be to limit the application rate (AR) f o r broadcast treatments on dormant bermudagrass to a maximum of 5 quarts / acre ( 1 .25 lb ai/ Acre)
. See assessment below. lfa ble 4. Re s id enti al Hand ler Non- can ce r Exposure an d Risk Estima t e s for App l icati o n of Glu fosinate- !Ammo n ium o n R es identia l T ur f. Dermal Inhalation Area Treated Dermal Inhalation E x posu r e Unit Unit Maximum or Amount M OE 4 MOE6 Sce n ari o E xpo s ure Expo s ure App li cation Handled Do s e Dose ( mgllb ai) (mgllb ai ) Rate' Daill (mg/ kg/ da y) 3 (mg/ kg/ day) 5 LO C =IOOO LOC=3 00 Mixer / Loader / Applicator Ho s e - end S prayer 1 .2 5 lb (Broadcas t 1 3
. 4 0022 a i /acre 0
. 5 ac r es 0
. 0 109 1 , 300 0.0002 73,000 treatm e nt s )
Tab l e 5. Short- Term Aggregate Risk for Glufosinate Ammonium (hose end sprayer) scenario for residential mixer/loader/applicator (AR=1.25 lb ai/a cr e)

LOAEL Food+ Drinking P op ulation ( mg/ kg/ da y) Water Exposure ( mg/ kg/ day)
Genera l 1 4 0.00 2324 

### u.s. P op u l at ion LOC =Lev e l of Concern MO E = LOA EU Exposure D er mal Do se ( mg/ kg/ da y)

0.0 1 0 9

MO E Agj;rcg at c = LOAELI(Exposure roo dand wate r+ Exposurederm a J) Food + Drink in g Water exposure: See D3874l3 De rm al exposure: See Table 4.

Page 8 of8 Tota l Exp o s ur e ( mg/ kg/ da y)

0
. 0 1 322 LOC MOE Agg

10 00 1058Tab le 2. Recommendation s f o r th e R es id e ntia l Exposure s fo r t h e G luf os inat e-a mm o nium Ag gre gate A ss e ss m e nt 1 Res id e nti a l Handl er Res id e ntial P os t- a pplicatio n L if es t age Do s e( mglk g / day) 2 I M O E3 Dose ( m g/k g/d ay) 4 

### I M0 £ 5 Derma l 

### I Inh a l atio n 

### I T ota l 

### I Derm a l ! Inh a l at io n 

### I T ota l De rm a l 

### I Inh a l atio n 

### I Or al 

### I T ota l 

### I Dermal 

### I I nh a la t ion 

### I Ora l 

### I To t a l Short-Term Ad u lt o . o t 3 

### I o . ooo2 1 

### I N / A 

### I 1 ,100 

### I 61 , 000 

### I N /A N /A 

### J N I A 

### I N /A 

### I N /A _I N / A I N /A I N /A I N/ A C hild N I A N I A 

### I N / A 

### I N/A 

### I N /A 

### I N /A 

### I N I A 

### I N /A 

### I N I A I Bo ld ed ri sk es timat es s h o ul d co ntribute t o the res ident i al expos ure p o rt ion o f th e a ggreg a te assess m en

t. 2 R es ide nt ia l Hand l e r Dose = th e hi g h es t hand l er d o se f o r each appli ca b l

e lif es t

age of all s c e n

ari os asses s e d fro m T abl e I
. To tal = de m1al + inhal a ti o n. 3 R es ide nt ia l Ha n dl

e r MOE = th e MOEs associated with th e hi ghest doses id entifi ed in Tabl e I. To t al = I + ( ! / Dermal MOE) + ( !/Inhalation MO E). 4 R es id e nt ia l Post-appli c ation Dose= th e high est post- app l i ca

ti o n d ose f or each a ppli cabl e li fcs tage o f all sce nario s as sessed
. To tal = dermal + i nhalati on + in ci d e ntal o r al. wher e appli ca bl e . R

es id e ntial Po s t
-appli c ati o n MO E = the MOEs associated with the hi g hes t d ose s identifi e d
. To tal = I + (! /Dermal MOE)+ (I !Inhalation MO E) + (! / In c id ental o r al) 

### Table 3. Short-Term Aggregate Risk for Glufosinate Ammonium (hose end sprayer) scenario for residential mixer/loader/applicator (AR = l.SO lb ai/acre)
Population LOAEL (mg/ kg / day)

Ge ner a l U.S. 14 Popu l atio n

------·---- ---------·- L

OC= L evc l o f C on ce rn MO E = L OAE L/Ex pos ure Food+ Drinking Water Expos ure (mg/kg/day)

0
. 00 2324

MOE Agg r egat e= LO AE U ( Exp os urer ood and water + E xposurede nn al) F

oo d + Drinkin g W ater ex p os ur e: See D3 87 413 D

e rm al ex pos ure: See T able 2. De rmal Dose Total Expos ure LOC MOE" u (mglkglday) ( mglkg/da y)

0
. 0 1 3 0.0 15 32 10 00 913



### Page 7 of8