UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

Date: October 29, 2013 

OFFICE OF 

CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

SUBJECT: Glufosinate Ammonium. Response to Comments on the Human Health Risk 

Assessment for Registration Review. 

PC Code: 128850 

Decision No.: 483601 

Petition No.: NA 

DP Bar code: D415395 

Registra tion No.: NA 

Regulatory Action: Registration Review 

Risk Assessment Type: Response to Case No.: NA 

Comments 

TXRNo.: NA 

MRIDNo.: NA 

CAS No.: 77182-82-2 

40 CFR: § 180.473 

FROM: 

John 

WilliamH.Donovan,Ph.D,Chem~·s Liccione, Ph.D., Toxicologist isF As LJ~CfJ ~~ 

Ana Rivera-Lupiafiez, Chemist · 

Risk Assessment Branch V 

Health Effects Division (HED) (7509P) 

Office ofPesticide Programs (OPP) 

THROUGH: Michael S. Metzger, Branch Chie#/ /} /J /} / _/ ~ Risk Assessment Branch V Nil t0K0A' (/ V 

HED/OPP (7509P) 

TO: Katie Weyrauch, Chemical Review Manager 

Risk Management and Implementation Branch 1 

Pesticide Re-Evaluation Division (7508P) 

Bayer CropScience (BCS) has submitted comments on the HED documents titled Glufosinate 

Ammonium. Human Health Risk Assessment for Registration Review (1/24113; D406360), and 

Human Health RiskAssessmentfor the Proposed New Use ofG/ufosinate Ammonium inion 

Citrus Fruit (Crop Group 10), Pome Fruit (Crop Group 1 1), Stone Fruit (Crop Group 12), 

Olives and Sweet Corn (7/25/12; D387413). In the present memo, each issue is briefly 

identified, followed by BCS's comments (from their submission dated 6/13/ 13 , Bayer 

CropScience Comments to EPA 's draft Human Health and Ecological Risk assessments for the 

Registration Review ofGlufosinate Ammonium, Federal Register Notice 2013-03-06, Vol. 78, 

No.44,· Pesticide Docket Identification No. EPA-HQ-OPP-2008-0190; No MRID No.), and the 

current HED response. 

Page 1 of 8 
Detailed 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 significant revision to the non-dietary exposure assessment. 

HED: The Agency has reviewed 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 "triple 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 critical criterion of the OPP guidance on using the "triple 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 

addition, the concentrations of test substance were different among the three studies, with the 

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. For 

glufosinate, the ratio 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 

different) 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 of8 
given 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 glufosinate 

ammonium since the post-application dermal MOEs are lower than 4000 (i.e. 4 X LOC) on Day 

0 (scouting and/or irrigation mature/high foliage 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 should 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 revised 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. 432-1229), Derringer Herbicide (432-1228) and 

Derringer F Herbicide (432-960) whenever the Agency deems it necessary. 

HED: This issue will be resolved once the missing information is added to the Finale® 

Herbicide (EPA Reg. No. 432-1229), Derringer Herbicide (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/gal glufosinate 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 labels 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, Brassica 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, 

Sweet Corn, Corn, Cotton, Rice, Soybeans and Sugar beets may be planted back at any time. 

HED: HED concurs with the 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 application to dormant Bermudagrass should be 

included in the glufosinate ammonium risk assessment. BCS analysis shows acceptable risk 

levels for this use pattern. 

Page 3 of8 
HED: HED concurs that an exposure assessment for use on dormant bermudagrass should be 

included in the glufosinate ammonium risk assessment. Although this use pattern results in risks 

below HED's level of concern when considered by itself, inclusion of this use pattern in the 

aggregate risk assessment results in risk estimates that exceed HED's level of concern unless the 

maximum use rate is reduced to 1.25 lb ai/A or less. The text below provides the details 

involved in reaching these conclusions. 

Residential (non-occupational) Exposure 

According to the 2012 HED's Residential SOPs (Lawns/Turf section) the quantitative 

exposure/risk assessment developed for residential handlers is based on the following exposure 

scenario: 

• Mixing/loading/applying liquids with a hose-end sprayer, 

Residential Handler Exposure Data and Assumptions 

Short-term dermal and inhalation exposures were assessed for residential handlers. A series of 

assumptions and exposure factors served as the basis for completing the residential handler risk 

assessments. Each assumption and factor is detailed below. 

Application Rate 

A maximum single application rate of 1.5 lb ai/acre (6 quarts/acre) was used for the broadcast 

treatment scenarios to residential turf(EPA Reg. No. 432-1229). 

Unit Exposures and Area/Amount Treated 

Unit exposure (UE) values and estimates for area treated were taken from HED's 2012 

Residential SOPs: Lawns/Turf. Note: the Registrant'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 weight 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 

penetration study (D289836, B. Daiss, 17-JUN-2003). For inhalation risk assessment, a route 

specific study was used. 

Exposure Duration 

Residential handler exposure is expected to be short-term. Intermediate-term exposures are not 

likely because of the intermittent nature of applications by homeowners. 

Endpoint Selection 

The endpoint to assess short-term dermal risk was brain morphometric changes in the 

developmental neurotoxicity study in rats. The endpoint to assess short- term inhalation exposure 

Page 4 of8 
was lung/bronchial congestion and increased lung/bronchi weight in females, and increased 

kidney and liver weights in a 28-day inhalation study in rats. 

Residential Handler Exposure and Risk Estimate Equations 

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

2012 Residential SOPs'. 

Summary of Residential Handler Non-Cancer Exposure and Risk Estimates 

In this assessment, since the Points of Departure (PODs) selected for dermal and inhalation 

routes of exposure are based on different endpoints; the MOEs for the dermal and inhalation 

exposure routes were not combined. Please note that BCS incorrectly used an Aggregate Risk 

Index (ARI) approach to assess risk. Short-term exposures and risk estimates for residential 

handlers performing broadcast treatments on bermudagrass do not exceed HED's level 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 handlers is 

included in Table 1. Updated residential exposure risk estimates are also provided for 

consideration in the aggregate risk assessment and presented on Table 2. 

frable 1. Residential Handler Non-cancer Exposure and Risk Estimates for Application of GlufosinateAmmonium on Residential Turf. 

Dermal Inhalation Area Treated Dermal Inhalation 

Exposure Unit Unit Maximum or Amount MOE4 MOE6 

Scenario Exposure Exposure Application Handled Dose Dose 

(mg/lb ai) (mg/lb ai) Rate1 

Daill (mg/kg/day)3 (mg/kg/day)

5 

LOC=tOOO LOC= 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/pesticides/science/residential-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 Dermal Absorption Factor (9%) .;. Body Weight (69kg). 

4 Dermal MOE = Dermal NOAEL ( 14 mg/kg/day) + Dermal Dose (mglkg/day). 

5 Inhalation Dose = Inhalation Unit Exposure (mg/lb ai) x Application Rate (lb ai/acre or gal) x Area Treated or Amount 

Handled (Alday or gallons/day) + BW (80 kg). 

6 Inhalation MOE= Inhalation NOAEL (12.5 mg/kg/day) + Inhalation Dose (mg/kg/day). 

Residential Post-Application Exposure 

Exposure is possible during post-application activities on treated turf. Children may experience 

exposure via incidental non-dietary ingestion (i.e., hand-to-mouth, object-to-mouth (turfgrass), 

and soil ingestion) during post-application activities on treated turf. Based on the Agency's 

current practices, post-application dennal assessments are not performed for spot treatment uses 

(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 application dermal exposure resulting from broadcast treatments to dormant bermudagrass 

was not quantified for homeowners or golfers because of the unique use pattern of glufosinate 

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

Page 5 of8 
ammonium. The herbicide is applied to dormant bermudagrass during the winter when the 

weather is generally cold and winter clothing is worn; therefore, post-application contact is likely 

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 negligible. 

Likewise, post-application inhalation exposure while engaged in activities on or around 

previously treated turf is generally not assessed. The combination of low vapor pressure for 

chemicals typically 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-application inhalation exposure assessment was not performed for glufosinate 

ammonium at this time primarily because it has very low vapor pressure (2.3 x 10-

7 mmHg at 

25°C). However, volatilization of pesticides may be a potential source of post-application 

inhalation exposure to individuals 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 Scientific Advisory Panel (SAP) in December 2009. The 

Agency received the SAP's final report on March 2, 2010 

(http://www.epa.gov/scipolv/SAP/meetings/200911 20 1 09meeting.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-application 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 post-application inhalation exposure assessment 

for glufosinate ammonium. However, it should be noted that residential handler inhalation 

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 of8 
Label Recommendation 

A risk mitigation option would be to limit the application rate (AR) for broadcast treatments on 

dormant bermudagrass to a maximum of 5 quarts/acre ( 1.25 lb ai/ Acre). See assessment below. 

lfable 4. Residential Handler Non-cancer Exposure and Risk Estimates for Application of Glufosinate-

!Ammon ium on Residential T urf. 

Dermal Inhalation Area Treated Dermal Inhalation 

Exposure Unit Unit Maximum or Amount MOE4 MOE6 

Scenario Exposure Exposure Application Handled Dose Dose 

(mgllb ai) (mgllb ai) Rate' Daill (mg/kg/day)

3 (mg/kg/day)5 

LOC=IOOO LOC=300 

Mixer/Loader/ Applicator 

Hose-end Sprayer 1.25 lb 

(Broadcast 13.4 0022 ai/acre 0.5 acres 0.0 109 1,300 0.0002 73,000 

treatments) 

Table 5. Short-Term Aggregate Risk for Glufosinate Ammonium (hose end sprayer) 

scenario for residential mixer/loader/applicator (AR=1.25 lb ai/acre) 

LOAEL Food+ Drinking 

Population (mg/kg/day) Water Exposure 

(mg/kg/day) 

General 14 0.002324 

u.s. 

Population 

LOC=Level of Concern 

MOE= LOAEUExposure 

Dermal Dose 

(mg/kg/day) 

0.0109 

MOE Agj;rcgatc= LOAELI(Exposurerood and water+ ExposuredermaJ) 

Food + Drinkin g Water exposure: See D3874l3 

Dermal exposure: See Table 4. 

Page 8 of8 

Total Exposure 

(mg/kg/day) 

0.0 1322 

LOC MOE Agg 

1000 1058 
Table 2. Recommendations for the Residential Exposures for t he Glufosinate-ammo nium Aggregate Assessment 1 

Residential Handler Residential Post-application 

Lifestage Dose(mglkg/day)2 I MOE3 Dose (mg/kg/day)

4 I M0£5 

Dermal I Inhalation I Total I Dermal ! Inhalation I Total Dermal I Inhalation I Oral I Total I Dermal I Inhalation I Oral I Total 

Short-Term 

Adult o.o t3 I o.ooo2 1 I N/A I 1,100 I 61 ,000 I N/A N/A J NIA I N/A I N/A _I N/A I N/A I N/A I N/A 

Child NIA NIA I N/A I N/A I N/A I N/A I NIA I N/A I NIA 

I Bolded risk estimates should contribute to the residential exposure portion of the aggregate assessment. 

2 Residential Handler Dose = the highest handler dose for each applicable lifestage of all scenarios assessed from Table I. Total = dem1al + inhalation. 

3 Residential Handler MOE = the MOEs associated with the highest doses identified in Table I. Total = I + (!/Dermal MOE) + (!/Inhalation MOE). 

4 Residential Post-application Dose= the highest post-application dose for each applicable lifcstage of all scenarios assessed. Total = dermal + inhalation + incidental oral. where 

applicable. 

Residential Post-application MOE= the MOEs associated with the highest doses identified. Total = I + (!/Dermal MOE)+ (I !Inhalation MOE) + (!/Incidental oral) 

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) 

General U.S. 14 

Population 

------·---- ---------·-

LOC=Levcl of Concern 

MOE= LOAEL/Exposure 

Food+ Drinking Water 

Exposure (mg/kg/day) 

0.002324 

MOE Aggregate= LOAEU(Exposurerood and water + Exposuredennal) 

Food + Drinking Water exposure: See D387413 

Dermal exposure: See Table 2. 

Dermal Dose Total Exposure LOC MOE"u (mglkglday) (mglkg/day) 

0.013 0.0 1532 1000 913 

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