Page 3 of 45

An acceptable 28

- day inhalation toxicity study demonstrated toxicity at the lowest dose tested as indicated by lung and bronchial effects and sli ght behavioral changes.

There is no concern for mutagenic activity based on the results of several mutagenicity studies

.

G lufosinate ammonium was classified as “not likely to be a human carcinogen

. ” There was no

evidence of a treatment

- related increase in tumors in either rats or mice.

Additional testing was conducted with the L

- isomer of glufosinate ammonium (HOE 058192), and degradates HOE 061517 (MPP) and HOE 09 9730 (NAG) . These compounds, tested in subchronic rat, mouse, and dog studies, and in de velopmental toxicity studies in rat and rabbit, are generally less toxic than the parent compound

. However, HOE 058192 was found to be slightly more toxic than the racemic parent compound. This finding is not a concern since this isomer is

included in th e toxicity testing of the parent compound at the levels in the technical material.

Endpoints for risk assessment were selected for dietary, dermal, and inhalation scenarios. The FQPA Safety Factor was reduced to 1× for acute dietary exposure only; thus a standard uncertainty factor of 100 × was used for the acute dietary risk assessment. An additional uncertainty factor of 10× was used for other exposure scenarios (total uncertainty factor of 1000 × ) because the studies selected for endpoint setting used L OAELs (the developmental neurotoxicity

and the 28

- day inhalation studies) and did not establish NOAELs.

Residue Chemistry

The nature of the residue in plants and livestock is understood. The residues of concern in plant and livestock commodities are parent, glufosinate propanoic acid , and N

- acetylglufosinate.

The registration requirements for magnitude of the residue in plants have been evaluated and

deemed fulfilled

. T he field trials on citrus fruits, pome fruits, stone fruits, olives, and sweet corn

are adequate. An adequate number of trials were conducted reflecting the proposed use patterns in the appropriate geographic regions, and the appropriate commodities w ere collected at t he proposed PHIs. However, the proposed use directions should specify the maximum application rate, the maximum number of applications, and the retreatment intervals. Samples were analyzed using validated analytical methods

. Processing studies were conducted on the appropriate

commodities and these results were taken into consideration in the recommended tolerance levels.

A cceptable analytical methods are available for enforcement of residue tolerances of glufosi nate
ammonium and metabolites in/on plant and livestock commodities

.

No increase in dietary burden results from the proposed uses; established tolerance levels in meat, milk, poul t ry and egg commodities remain appropriate.

Dietary Risk (Food and Drinking Water)

The Environmental Fate and Effects Division (EFED) provided a drinking water assessment for glufosinate ammonium. T he assessment evaluate d the maximum use patterns of the established and proposed new uses of glufosinate ammonium. Based o n maximum use patterns, the peak and

1

- in

- 10

- year annual mean estimated drinking water concentrations ( EDWC s) are 390 and 95 ppb, respectively, driven by the rice use. The drinking water exposure estimates are lower for all other

uses.Page 4 of 45

An acute dietary exposure assessment for glufosinate ammonium was conducted for the only relevant population subgroup, females 13

- 49 years old. A screening level assessment made use of tolerance level residues, 100% crop treated assumptions, default processing factors and an acute
EDWC of 390 ppb. This acute dietary exposure estimate gave results below HED’s level of

concern (LOC) , with the females 13

- 49 year old population subgroup at 39 % aPAD.

The chronic dietary exposure assessment for glufosinate ammonium is refine d using anticipated

residues based on average residue levels from crop field trials. Percent crop treated (%CT) information and processing factors, where available, were used in the assessment. The chronic dietary risk assessment for glufosinate ammonium at an EDWC of 9 5 ppb showed that chronic dietary risk estimates are below HED ’s LOC (<100% cPAD) for infants (<1 year old), the highest exposed population subgroup ( 98 % of the cPAD) , as well as for the general US population (3 9 % of the cPAD).

Non

- Occupational and Residential Risk

The current petition for glufosinate ammonium results in no non

- occupational/residential

exposures. P ost

- application short

- term dermal and inhalation exposures to adult homeowners are possible based on the existing s pot treatments to turf ; however, these exposures are expected to be low and current Agency practice does not routinely require these assessments

. In contrast, residential handler assessments are needed for spot treatments to turf. The inhalation margins of exposure ( MOE s ) for all potential exposure scenarios are greater than 300 , the inhalation LOC

. Similarly, the dermal MOEs for all potential exposure scenarios related to turf spot treatments are greater than 1000, the dermal LOC.

Aggregate Risk

An a gg regate exposure risk assessment was conducted by incorporating drinking water directly into the dietary exposure assessment for the following scenarios: acute, chronic

, and short

- term
aggregate exposure. The short

- term aggregate exposure risk assessme nt also included residential exposure estimates. Intermediate

- and long

- term residential exposures are not anticipated ;

t herefore intermediate

- /long

- term aggregate risk assessment s were not performed. C ancer aggregate

- risk assessments were not performed because glufosinate ammonium is not likely carcinogenic.

Acute aggregate risk estimates are identical to the acute dietary risk estima tes and do not exceed

HED’s LOC

. Chronic aggregate risk estimates are identical to the chroni c dietary risk estimates

and do not exceed HED’s LOC

.

Using average food and water exposures together with residential exposures from turf spot

treatments , the short

- term aggregate MOE is estimated as 1 8 00, which is greater than the target

MOE of 10 0 0. For residential exposures, only the dermal route of exposure was included in the aggregate analysis since potential dermal exposures are higher than potential inhalation exposures; it is not appropriate to aggregate the dermal and inhalation exposures sinc e the toxicity endpoints are different. Therefore

, the short

- term aggregate risk exposure estimate is not of concern to the Agency as it does not exceed HED’s LOC ( MOEs less than or equal to 100 0 ).Page 5 of 45

Occupational Exposure and Risk

Results from the asse ssment of all occupational handler scenarios

, with the exception of mixer/loader/applicator (MLAP) spot treatments scenarios with mechanically pressurized handgun, indicate that short

- and intermediate

- term dermal and inhalation risks are not of concern

to HED. S hort

- and intermediate

- term risks for spot treatment MLAP scenarios with mechanically pressurized handgun are of concern to HED even with the addition of personal protection and/or engineering controls.

Post Occupation al Exposure and Risk

Results of the glufosinate ammonium post

- application exposure and dermal risk assessment for

sweet corn indicate that an MOE of 1,050 is not achieved until Day 4 for irrigation of mature/high foliage plants; therefore, this post

- appli cation activity is of potential concern to the Agency at
shorter re

- entry intervals ( REIs ) . The proposed Liberty® Herbicide label indicates an REI of 12

hrs

. T his timing needs revision to achieve an MOE above the target of 1000 based upon the post

applica tion exposure estimates obtained for sweet corn.

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 (AHETF) database; the Outdoor Residential Exposure Task Force (ORETF) database; and the Agricultural Re

- entry Task Force (ARTF) database; are subject to ethics review pursuant to 40 CFR 26, have received that revie w, 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

- exposure

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

- app

- exposur e

- data.html

2.0 HED Recommendations

HED recommends for a registration and tolerance s for the use of glufosinate ammonium in/on citrus fruit, pome fruit, stone fruit, olives, and sweet corn. The specific tolerance

recommendations are provided in Section 2.2, and label modifications are listed in Section 2.3.

2.1 Data Deficiencies

None

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

There are adequate residue analytical methods for tolerance enforcement. Also, t he method s used

for data collection were adequate based on the method recoveries , precision and the range of

levels tested

.Page 6 of 45

Two analytical methods have been validated by the Analytical Chemistry Branch (ACB) for enforcement of the currently established tolerances : (1) method HRAV

- 5A was validated by ACB for the determination of glufosinate ammonium and glufosinate propanoic acid in/on apple, grape, almond, soybean seed, corn grain, and corn forage (PP# 8F3607, J. Garbus, 14

- Sep

- 1989)

and (2) method BK/01/99 was v alidated by ACB for determination of glufosinate ammonium, N

acetyl

- glufosinate, and glufosinate propanoic acid in/on canola seed and sugar beet root (D258420, T. Bloem, 19

- Aug

- 2000). Both methods involve extraction with water, anion

exchange chromatograp hy, derivatization with trimethylorthoacetate, silica

- gel column clean

- up, and quantification via gas chromatography with flame photometric detection (residues expressed as glufosinate free acid equivalents). Method BK/01/99 includes a cation ion

- exchange column prior to derivatization which fractionates glufosinate ammonium and N

- acetyl

- glufosinate and allows for speciation of these compounds (both compounds are derivatized to the same compound). This step can be eliminated if separation of these two com pounds is unnecessary. The methods do not distinguish between the D and L enantiomers of glufosinate ammonium and

N

- acetyl

- glufosinate.

Based on the similarity in the two methods and the results from the petition method validations (PMVs), HED concludes that adequate enforcement methods are available for sweet corn, stone fruit, pome fruit, citrus fruit and olive.

2.2.2 Recommended Tole rances

The tolerance expression under 40 CFR §180.473 should be revised to read as follows:

Tolerances are established for residues of glufosinate ammonium , including its metabolites and degradates, in or on the commodities in the table below. Complia nce with the tolerance levels specified below is to be determined by measuring the sum of glufosinate ammonium (butanoic acid, 2

- amino

- 4

- (hydroxymethylphosphinyl) monoammonium salt) and its metabolites, 2

- (acetylamino)

- 4

- (hydroxymethyl phosphinyl) butanoic acid

, and 3

- (hydroxymethylphosphinyl) propanoic acid , expressed as 2

- amino

- 4

- (hydroxymethylphosphinyl)butanoic acid equivalents :

Table 2.2.2 Tolerance Summary for Glufosinate Ammonium

. Commodity Proposed Tolerance (ppm) Recommended

Tolerance (ppm) Comments

Citrus (CG 10) 0.05 0.15 Fruit, citrus, group 10

- 10

Pome Fruit (CG 11) 0.10 0. 25 Fruit, pome, group 11

- 10

Stone Fruit (CG 12) 0.10 0. 25 Fruit, stone, group 12

- 12

Olives 0.05 0.1 5

Corn, sweet, kernels plus cob

with husks removed 0.2 0.30

Corn, sweet, f

orage 4.0 1.5

Corn, sweet, s tover 6.0 6.0

Plum, p rune , dried 0.20 None Covered by the Stone Fruit

tolerance.

2.2.3 Revisions to Petitioned

- For Tolerances

HED recommends higher tolerance levels for citrus, pome fruit, stone fruit, and olives due to summation of the full LOQ for each of the three residues of concern in situations where <LOQPage 7 of 45

residue levels were found. The recommended sweet corn tolerances are based on the OECD tolerance calculation procedures. No separate prune tolerance was recommended as residues in this processed commodity are covered by the stone fruit group tolerance.

2.2.4 International Harmonization

The Codex Alimentarius Commission has not established maximum residue l imits (MRLs) for glufosinate ammonium in/on olives and sweet corn commodities

. However, for glufosinate ammonium in/on citrus fruit, pome fruit and stone fruit, Codex has set MRLs of 0.1, 0.05, and 0.05 ppm, respectively. The recommended US tolerances for citrus fruit, pome fruit, and stone fruit, are 0.15, 0.25 and 0.25 ppm, respectively. The US tolerance values for these commodities is higher tha n the Codex MRL; t herefore, harmonization of the US tolerances with the Codex MRLs

is not possible with this petition because MRLs could be exceeded with the proposed uses

. There are no MRLs established in Mexico or Canada for the use of glufosinate ammon ium on the commodities under the current petition.

2.3 Label Recommendations

2.3.1 Recommendations from Residue Reviews

Crop use pattern information should include maximum single and seasonal use rates, re

treatment intervals ( RTI s)

, and pre

- harvest in tervals ( PHI s)

.

2.3.2 Recommendations from Occupational Assessment

Short

- and intermediate

- term risks for mixer/loader/applicator (MLAP) scenarios with mechanically pressurized handgun for spot treatments on olives, citrus, pome, and stone fruit are of concern to the Agency even with the addition of personal protection to mitigate exposure such as: extra layer of clothing (coveralls), glove s and PF10R respirator.

The proposed Liberty® Herbicide label indicates an REI of 12 hrs; however, this timing

needs revision to 4 days based upon the post

- application exposure estimates obtained for

sweet corn in order to achieve an MOE which exceeds th e target MOE = 1000.

2.3.3 Recommendations from Residential Assessment

Since glufosinate ammonium is not a restricted use pesticide it is recommended that all labels that could potentially be used by homeowners clearly restrict lawn/turf uses to

spot tr eatments only. The maximum application rate should not exceed 4 fl ounces per gallon of water per 1,000 square feet.

3 .0. Introduction

T he nomenclature and physicochemical properties of glufosinate ammonium a re presented below

in Tables 3 .1 and 3 .2

.

3 .1

. Chemical IdentityPage 8 of 45

TABLE 3 .1 . Test Compound Nomenclature.

Compound

Common name Glufosinate ammonium

Company experimental name AE F039866 , HOE 039866

IUPAC name ammonium (2 RS )

- 2

- amino

- 4

- (methylphosphinato )butyric acid

CAS name 2

- amino

- 4

- (hydroxymethylphosphinyl)butanoic acid monoammonium salt

CAS registry number 77182

- 82

- 2

End

- use product (EP) RELY 200 SC

Compound

Common name Glu

- PPA, AE F061517, Glufosinate propanoic acid , HOE 061517 , MPP

Chemical name 3

- methylphosphinico

- propionic acid or

3

- (h ydroxymethylphosphinyl) propanoic acid

Compound

Common name Glu

- NAG, AE F085355, N

- acetylglufosinate , HOE 099730 , NAG

Chemical name 2

- (a cetylamino)

- 4

- (hydroxymethyl phosphinyl) butanoic acid

Compound

Common name HOE 064619, Glufosinate acetic acid , MPA

Chemical name 2

- methyl phophinico acetic acid

3 .2 . Physical/ Chemical Characteristics

Table 3

. 2

. Physicochemical Properties of the Technical Grade Test Compound.

Parameter Value 1

Melting point/range (°C) 215

- 218

pH 4.7

Density (g/cm 3 ) 1.32
Water solubility (g/L at pH 5) 1370

Solvent solubility at room temp (g/L) methanol: 5.73; DMSO: 0.049; polyethylene glycol: 0.047;

aceton it rile, toluene, acetone, ethyl acetate, and hexane: <0.00025Page 9 of 45

Table 3

. 2

. Physicochemical Properties of the Technical Grade Test Compound.

Parameter Value 1

Vapor pressure at 25 °C (mPa ) 0.031

Dissociation constant, pK

a 9.15
Octanol/water partition coefficient (Log K OW )

- 4.01

UV/visible absorption spectrum (nm) >190

1 Source: 46573701 .der.doc, T. Bloem, 2005

Based on its physical

- chemical properties, glufosinate ammon ium is highly water soluble, non

volatile , and a weak acid

.

3.3 Pesticide Use Pattern

Table 3.3 summarizes the proposed use patterns for the new crop uses requested in the current petitions.

Table 3.3 Summary of Directions for Use of Glufosinate Ammonium (2.34 lb/gal; EPA Reg. No. 352

- 515)

. 1

Applic. Timing, Type, and Equip. Applic. Rate

(lb ai/A) Retreat.

Interval (days) Max. No. Applic . Per

Season Max. Seasonal

Applic. Rate (lb ai/A) PHI

(days) Adjuvant Use Directions

and Limitations

Broadcast,

banded or
spot treatment Stone Fruit Do not apply this product through any type of irrigation system.

Do not apply this product aerially.

Do not graze, harvest, and/or

feed treated

orchard cover

crops to livestock.

Do not make spot spray applications

to suckers. 1.5 28 2 3.0 14 non

- ionic

antifoam 2

Pome Fruit

1.5 14 3 4.5 14 non

- ionic

antifoam 2

Citrus

1.5 14 3 4.5 14 non

- ionic

antifoam 2

Olives

1.5 14 3 4.5 14 non

- ionic

antifoam 2

Foliar

treatment Transgenic Sweet Corn Must be applied

with ammonium

sulfate. 0.3 65 14 2 0.73 50 None

1 The listing s in bold are not in the label but correspond to the field trial use pattern s

. 2 A non

- ionic antifoam adjuvant may be added.

See Section 2.3 for recommended modifications to the proposed label.

3.4 Anticipated Exposure Pathways

The Registration Division has requested an assessment of human health risk to support the proposed new uses of glufosinate ammonium in/on a variety of crops. Humans may be exposed to glufosinate ammonium in food and drinking water, since it may be applied directly to growing crops and application may result in glufosinate ammonium reaching surface and ground water sources of drinking water. There are registered residential turf uses (limited to spot treatments)Page 10 of 45

that may lead to homeowner exposures . In an occup ational setting, applicators may be exposed while handling the pesticide prior to application, as well as during application. There is a potential for post

- application exposure for workers re

- entering treated fields.

Risk assessments have been pr eviously conducted for glufosinate ammonium and the only new toxicity study received since the last risk assessment was the immunotoxicity study, which demonstrated effects only at higher doses than selected as points of departure in the earlier risk

asses sments. A detailed description of the toxicity data and metabolism information may be

found in the risk assessment dated 12/15 /2010 (W. Donovan et. al. , D372623). The current risk assessment considers all of the aforementioned exposure pathways based on the proposed new uses of glufosinate ammonium, but also considers the existing new uses as well, particularly for the dietary and residential exposure assessments.

3.5 Consideration of Environmental Justice

Potential areas of environmental justice con cerns, to the extent possible, were considered in this

human

- health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions to Address Environmental Justice in Minority Populations and Low

- Income Populations," ( http://homer.ornl.gov/nuclearsafety/nsea/oepa/guidance/justice/eo12898.pdf ).

As a part of every pesticide risk assessment, OPP considers a large variety of consumer subgroups according to well

- established procedures. In line with OPP policy, HED estimates risks to population subgroups from pesticide exposures that are based on patterns of that subgroup’s food and water consumption, and activities in and around the home that involve pest icide use in a residential setting. Extensive data on food consumption patterns are compiled by the USDA

under the National Health a nd Nutrition Examination Survey /“What We Eat in America” (NHANES/WWEIA)

, and are used in pesticide risk assessments for all registered food uses of a pesticide. These data are analyzed and categorized by subgroups based on age, season of the year, ethnic group, and region of the country. Additionally, OPP is able to assess dietary exposure to smaller, specialized subgroups a nd exposure assessments are performed when conditions or circumstances warrant. Whenever appropriate, non

- dietary exposures based on home use of pesticide products and associated risks for adult applicators and for toddlers, youths, and adults entering or playing on treated areas post

- application are evaluated. Further considerations are currently in development as OPP has committed resources and expertise to the development of specialized software and models that consider exposure to bystanders and farm workers as well as lifestyle and traditional dietary patterns among specific subgroups

.

4 .0 HAZARD CHARACTERIZATION

T he existing toxicological database for glufosinate ammonium is adequate to support the existing and proposed uses

. The registrant recently submitted an acceptable immunotoxicity study that previously had been identified as a data gap (D390963, J. Doherty, 28

- OCT

- 2011). The following information includes summaries of prior assessments (D372623, W. Donovan et. al.

, 15

- DEC

- 2010).

4.1 Summary of Toxicological Effects

There are several pharmacokinetic studies with glufosinate and they render similar results.

Glufosinate is eliminated via the excreta with 95

- 98% in the first 24 hours. The feces is the major

route of excretion with 88% i n males and 84% in females of the administered dose recovered inPage 11 of 45

the feces. Parent compound (~88% in males and ~74% in females) was the principle compound found in the excreta indicated that glufosinate is poorly absorbed from the gastro intestinal tract. The only metabolite found at > 1% of the administered dose was HOE 061517 (representing < 2% of the dose) in both the urine and feces. Tissue retention of label resulting from administration of radio labeled glufosinate was not remarkable in the kidneys , liver

, or gonads with residual values not much above background level following a single dose ; more was found following repeated

dos ing

.

For subchronic toxicity in rats, inhibition of glutamate synthetase was noted at the LOAEL. The HED Hazard Identification Assessment Review Committee (HIARC, HED Document TXR No.: 0051833, April 17, 2003) concluded that the changes in brain glutamine synthetase activity are of significant concern for possible neurotoxicity and/or expression of cl inical signs. However, the alterations in liver and kidney glutamate synthetase are considered an adaptive response. The primary effects in the mouse subchronic study were increased liver and kidney weights with increases in serum aspartate amino transfe rase and alkaline phosphatase.

In the chronic studies in the rat, inhibition of brain glutamine synthetase

, increased mortality,

and increased occurrence of retinal atrophy were noted, as were increased liver and kidney weights. In the mouse, increas ed mortality was noted, as were changes in glucose levels consistent with changes in glutathione levels. Increased mortality and electrocardiogram (EKG) alterations were observed in dogs. There was no evidence of a treatment

- related increase in

tumors in the rat or mouse carcinogenicity studies.

The developmental toxicity study in the rat produced dilated renal pelvis and/or hydroureter in the

fetuses at levels that produced significant increases in hyperactivity and vaginal bleeding in dams.

In the rab bit, decreased fetal body weight and increased mortality were observed at 20 mg/kg/day, while in rabbit dams, decreased food consumption, body weight, and body weight gain were observed at 20 mg/kg/day. Since increased fetal mortality was observed in the presence of less

severe maternal toxicity in the rabbit developmental study, there is evidence of qualitative increased susceptibility in fetuses

.

The reproductive toxicity study in rats indicated postnatal developmental toxicity at the highest

dose teste d (HDT) in the form of decrease in viable pups. No parental toxicity was seen at the HDT. Since pup mortality was observed in the absence of parental toxicity, there is evidence of quantitative increased susceptibility in offspring. However, the suscept ibility was only observed at the highest dose tested, which is 3.3 times higher than the point of departure used for the risk

assessment.

There were indications of neurotoxicity in several studies. Of particular concern is that the developmental neurotox icity study demonstrated alterations in brain morphometrics in the adult offspring exposed in utero or during lactation at dose levels not associated with maternal toxicity. Retinal atrophy was observed in the rat oral subchronic study. In the 90

- day die tary neurotoxicity study, increases in the incidence of decreased exploratory activity, decreased alertness, and decreased startle response, increased incidence of fearfulness, increased pain response and meiosis were reported. The subchronic dermal toxic ity study indicated aggressive behavior, a high startle response and piloerection. The 28

- day subchronic inhalation study demonstrated

tono

- clonic convulsions at the high dose in at least some males. However, in a 37

- day dietary neurotoxicity study, ther e was no evidence of neurotoxicity at doses up to 143.3 mg/kg/day. There was no evidence of neurotoxicity in two acute neurotoxicity studies at doses up to 500 mg/kg/day. Also, there was no evidence of neurotoxicity in White Leghorn hens following anPage 12 of 45

acu te dose of up to 10000 mg/kg. Changes in glutamine synthetase levels were observed in liver, kidney, and brain in rats. The altered electrocardiograms see n in the dog studies imply a possible

neuromuscular effect.

A 28

- day inhalation toxicity study wit h glufosinate ammonium generated from a powder technical grade product is available but it is classified as unacceptable due to the particle size exceeding guideline criteria. This study indicates a concern for exposure via the inhalation route

because it suggested that animals are more sensitive to effects by the inhalation route. A later

second 28

- day inhalation toxicity study was provided but this study assessed an aerosol generated from an aqueous technical product. The study was determined to have a tmospheric particles within the guideline criteria and was classified as Acceptable/Non

- Guideline. It was considered

non

- guideline because it was for only 28 and not 90 days duration. The LOAEL was unexpectedly greater than the previous study with the un acceptable particle size. HED considers that differences in pH of each test material may contribute to the differences in expression of toxicity since the first study assessed a powder with near neutral pH and the second study assessed an aqueous preparat ion with pH of 4.9. The pH conditions of the test material regulate the conversion of ammonium to ammonia; further, the potential for glufosinate to inhibit ammonia clearance may amplify the toxicity of inhaled ammonia.

There is no concern for mutagenic activity in several studies including: Salmonella E. Coli, in

vitro mammalian cell gene mutation assays, mammalian cell chromosome aberration assays, in

vivo mouse bone marrow micronucleus assays, and unscheduled DNA synthesis assays.

There is also no concern for immunotoxicity based on review of the series 870.7800 immunotoxicity study.

Consistent with the 2003 risk assessment (D290086, T. Bloem et. al. , 07

- AUG

- 2003) and ToxSAC recommendation (J. Kidwell, 29

- JUN

- 2010), a dermal abso rption factor of 9% was assumed, based on a dermal absorption study in male rats (D289836, B. Daiss, 17

- JUN

- 2003).

4.2 Safety Factor for Infants and Children (FQPA Safety Factor)

When the DNT study is used as an endpoint for risk assessment

, an extra 10× database uncertainty (UF L ) factor is applied because the DNT study did not demonstrate a NOAEL for altered brain morphometrics. This additional uncertainty factor will also account for indications of increased qualitative or quantitative sensitivity e vident in the rat and rabbit developmental

studies

, and the rat multigenerational reproduction study. Similarly, a UF L was applied to the inhalation exposure scenarios becaus e the 28

- day inhalation study in the rat did not identify a

NOAEL

. The toxicity and exposure data bases for glufosinate ammonium are otherwise complete. Acute, subchronic, and developmental neurotoxicity studies are available, and all endpoints used in this risk assessment are protective of neurot oxic effects when the extra 10× UF L is applied. The dietary, occupational, and residential assessments are based on reliable data and will not underestimate exposure.

4.2.1 Completeness of the Toxicology Data Base

The toxicity data base for the evaluation sensitivity/susceptibility to infa nts and children is complete. No additional studies are required at this time. The toxicity data base consists of acutePage 13 of 45

and subchronic neurotoxicity screen studies, a developmental neurotoxicity study, rat and rabbit developmental studies, a rat multi

- ge neration reproduction study and an immunotoxicity study.

4.2.2 Evidence of Neurotoxicity

A critical indication of neurotoxicity was evident in the developmental neurotoxicity study where alterations in brain morphometrics in the adult offspring were demo nstrated.

The clinical signs seen in rat or dog studies were varied and included hyperactivity, aggressive behavior, tonoclonic convulsion, piloerection, high startle response, and reti nal atrophy. In a 90

- day dietary neurotoxicity study, increases in the incidence of decreased exploratory activity, decreased alertness, decreased startle response, increased incidence of fearfulness, increased pain response and meiosis were observed.

4.2.3 Evidence of Sensitivity/Susceptibility in the Developing Yo ung Animal

In the DNT, alterations in brain morphometrics in adults following in utero exposure was evident at the lowest dose tested and at a dose level where there was no maternal toxicity. Thus, there is

evidence of quantitative increased sensitivity i n the rat.

In t he multi

- generational reproductive toxicity study in rats

, pup mortality was observed in the absence of parental toxicity. Thus, there is further evidence of quantitative increased susceptibility in offspring in rats. However, the suscep tibility was only observed at the hi ghest dose tested, which is 3.3× higher than the point of departure used for the risk assessment.

In the rabbit, decreased fetal body weight and increased mortality were observed at 20 mg/kg/day, while in rabbit dams, decreased food consumption, body weight, and body weight gain were observed at 20 mg/kg/day. Since increased fetal mortality is more se vere that the responses in the dams, there is evidence of qualitative increased susceptibility in the rabbit offspring.

The developmental toxicity study in the rat produced dilated renal pelvis and/or hydroureter in the offspring at levels that produced si gnificant increases in hyperactivity and vaginal bleeding in dams. Since effects occurred in the pups and dams at the same dose, this study is not considered to demonstrate either increased qualitative or quantitative sensitivity in the rat.

4.2.4 R esidual Uncertainty in the Exposure Database.

There are no residual uncertainties in the exposure database. Although the chronic dietary exposure estimates are partially refined, HED does not believe that the exposure estimates are

underestimated. These assumptions and refinements are detailed in Section 5.4.3. With limited monitoring data available, upper

- bound assumptions were used to determine exposure through drinking water sources.

4.3 Toxicity Endpoint and Point of Departure Selections

There have been no changes to the prior dose

- response assessment, recommendations for combining routes of exposure

, or the cancer classification. Table 4.3.1 presents a summary of the toxicological doses and endpoints used in the dietary, residential, and occupational risk

assessment s . A 10 X uncertainty factor

, attributable to the DNT study not demonstrating a

NOAEL

, should be applied to chronic dietary and residential dermal assessments. ForPage 14 of 45

occupational and residential inhalati on exposure asse ssments, a 10X database uncertainty factor should be applied due to the inhalation study not demonstrating a NOAEL

.

Table 4

. 3 .1 Summary of Toxicological Doses and Endpoints for Glufosinate Ammonium for Use in Dietary and Non

- Occupationa l and Occupational Human Health Risk

Assessments

Exposure/

Scenario Point of

Departure Uncertainty/FQPA

Safety Factors RfD, PAD,

Level of

Concern for

Risk

Assessment Study and Toxicological Effects

Acute Dietary (General Population

, including

Infants and Children) An endpoint attributable to a single exposure was not available from the toxicity studies, including

the developmental toxicity and developmental neurotoxicity studies.

Acute Dietary (Females 13

- 49 years of age) NOAEL =

6.3 mg/kg/day UF A = 10×

UF H =10× FQPA SF= 1×

Total UF = 100 × Acute RfD =

0.063 mg/kg/day

aPAD=0.063 mg/kg/day Developmental Toxicity Study in Rabbits

LOAEL = 20 mg/kg/day based on

increased fetal deaths.

Chronic Dietary (All Populations) NOAEL= 6

mg/kg/day UF A =10×

UF H =10× FQPA SF = UF L = 10×

Total UF = 1000× Chronic RfD =

0.006 mg/kg/day

cPAD = 0.006 mg/kg/day “Weight of evidence” approach from four

studies. Rat subchronic and chronic

studies with the LOAEL based on inhibition of brain glutamate synthetase. A dog chroni c study with the LOAEL based on altered electrocardiogram and mortality . The rat developmental neurotoxicity study with a LOAEL (without a NOAEL, basis for UF L ) based on altered morphometrics in the offspring

as adults.

Incidental Oral

Short

- Term (1

- 30 days) and

Intermediate term (1

- 6 months) LOAEL= 14

mg/kg/day (LDT) UF A =10×

UF H =10× FQPA SF= U F L = 10×

Total UF = 1000 × Residential

LOC for MOE

= 1000 Developmental Neurotoxicity Study in

Rats LOAEL = 14 mg/kg/day based on brain morphometric changes at PND 72. No

NOAEL identified.

Dermal

Short

- Term (1

- 30 days), and

Intermediate

Term (1

- 6 months) LOAEL= 14

mg/kg/day (LDT) UF A =10×

UF H =10× FQPA SF= UF L = 10×

Total UF = 1000 × Residential and

Occupational

LOC for MOE

= 1000 for

short and

intermediate

term exposures Developmental Neurotoxicity Study in

Rats

LOAEL = 14 mg/kg/day based on brain morphometric changes at PND 72. No

NOAEL identified.Page 15 of 45

Table 4

. 3 .1 Summary of Toxicological Doses and Endpoints for Glufosinate Ammonium for Use in Dietary and Non

- Occupationa l and Occupational Human Health Risk

Assessments

Exposure/

Scenario Point of

Departure Uncertainty/FQPA

Safety Factors RfD, PAD,

Level of

Concern for

Risk

Assessment Study and Toxicological Effects

Inhalation Acute, Short

Term (1

- 30 days),

intermediate (1

- 6 months) LOAEL=12.5

mg/kg/day (56 mg/m3) UF A = 3×

UF H =10× FQPA SF= UF L = 10×

Total UF = 3 00 × Residential and

Occupational

LOC for MOE

= 300 for short

and

intermediate

term 28

- day Inhalation Study (MRID

47058101) 2007 LOAEL = 12.5 mg/kg/day based on lung/bronchial congestion and increased lung/bronchi weight in female rats and increased kidney and liver weights.

Cancer (oral, dermal, inhalation) Classification: “Not likely to be Carcinogenic to Humans” based on the absence of significant

tumor increases in two adequate rodent carcinogenicity studies.

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 low er environmentally relevant human exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = potential variation in sensiti vity among members of the human population (intraspecies). UF L = use of a LOAEL to extrapolate a NOAEL

. FQPA SF = FQPA Safety Factor. PAD = population adjusted dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of exposure. LOC = level of concern. N/A = not applicable.

5.0 Dietary Exposure and Risk Assessment

5.1 Residues of Concern Summary and Rationale

No plant or animal metabolism data were submitted with the subject peti tions. The nature of the residue of glufosinate ammonium in livestock and plants has been adequately delineated. HED has previously reviewed metabolism studies conducted with nontransgenic (corn, soybean, apple, and lettuce; 8F3607, J. Garbus, 14

- Oct

- 198 8 & 8

- Aug

- 1990) and transgenic (corn, soybean, sugar beet, canola, and rice; D227386, M. Rodriguez,7

- Mar

- 1996; D257629, T. Bloem, 9

- Jul

- 1999; 45204405.der.wpd) crops. The transgenic corn, soybean, sugar beet, canola, and rice investigated

in the metabolis m studies were engineered to express PAT which acetylates glufosinate (herbicidally active) to form N

- acetyl

- glufosinate (not herbicidally active).

Based on the metabolism and magnitude of the residue studies, the Metabolism Assessment Review

Committee (MARC) concluded that the residues of concern in plants and livestock, for tolerance expression and risk assessment purposes, are glufosinate ammonium, N

- acetyl

- glufosinate, and glufosinate propanoic acid (D282757, T. Bloem, 9

- May

- 2002). HED concludes tha t the results from the currently available metabolism studies may be translated to citrus fruit, pome fruit, stone fruit, olive, and sweet corn.

The residue of concern in drinking water was considered at a meeting of the Residue of Concern Knowledgebase S ubcommittee (ROCKS) (D397644, I. Negrón

- Encarnación , 29

- MAR

- 2012). The ROCKS noted that MPP may have different toxicity than the parent and is likely to have a lower toxicity, but not so low that it could be definitely excluded from consideration. After thePage 16 of 45

ROCKS meeting, the team consulted with Health Effects Division Toxicology Science Advisory Council (ToxSAC) regarding the toxicity of MPP (J. Kidwell, 02/21/2012). The consensus of the

ToxSAC was that glufosinate ammonium and MPP show different toxici ties, such that they should not be aggregated. Because MPP is less toxic than glufosinate ammonium and should not be aggregated with it , if MPP EDWCs are not more than 4

- 5× greater than those for glufosinate, the risk assessment for the parent will be pro tective of any toxicity associated with exposure to MPP in drinking water. Indeed , the Environmental Fate and Effects Division has indicated that

the acute and chronic concentrations of MPP are not likely to be more than twice the corresponding levels of glufosinate ammonium in drinking water (see Table 5.1 )

. Therefore, a quantitative risk assessment for MPP in drinking water is not needed. Table 4.2.1 summarizes the nature of the residue decisions for glufosinate ammonium.

Table 5.1 . Summary of Metabo lites and Degradates to be included in the Risk Assessment and Tolerance Expression

Matrix Residues included in Risk

Assessment Residues included in Tolerance Expression

Plants Primary and

Rotational Crops Glufosinate ammonium,

glufosinate propanoic acid,

and N

- acetylglufosinate Glufosinate ammonium, glufosinate propanoic acid,

and N

- acetylglufosinate

Livestock Ruminant Glufosinate ammonium, glufosinate propanoic acid,

and N

- acetylglufosinate Glufosinate ammonium, glufosinate propanoic acid,

and N

- acetylglufosinate Swine Poultry Drinking Water Glufosinate ammonium 1 Not applicable

1 Since MPP has a different toxicity profile than the parent compound , it should not be aggregated with the parent

. Because MPP EDWCs are not significantly greater than those for glufosinate, the risk assessment for the parent is protective of any toxicity associated with expo sure to MPP in drinking water

, and a quanti tative risk assessment for

MPP is not required.

5 .2 Food Residue Profile

A review of the residue chemistry data submitted in conjunction with the current petition is provided in D3 72625 (I. Negrón

- Encarnación , 31

- AUG

- 2010 ). Specific information regarding the magnitude of the residue data and tolerance derivat ions is provided in Appendix B.

No adjuvant effects were discern ible in any of the field trials, which are supported by adequate storage stability data . The trials were adequate with respect to number and location.

Processing studies were performed for orange, plum and olive commodities. Details concerning the processing studies are in the following reviews: orange (47915706.der.wpd), plum (47915707.der.wpd) and olive (47915708.der.wpd). These studies are considered acceptable and

demonstrated no concentration in any processed commodity except for prune, where concentration

factors for GA, MPP, and NAG were <1.0× , 2.5 ×, and <1.0× , respectively. Multiplying the field trial HAFT values for plum by the concentration facto rs for prune gives: <0.05 pp m × <1.0 + 0.0655 ppm × 2.5 + <0.05 ppm × <1.0 = <0.26 ppm. Because the residue concentration in prunes is covered by the plum RAC tolerance level of 0.25 ppm, no separate prune tolerance is needed.Page 17 of 45

Except for sweet corn, there are no livestock feedstu ffs associated with the proposed new use crops. Inclusion of sweet corn does not result in an increase in the dietary burden from what was previously determined (D271110, T. Bloem, 20

- June

- 2002). Accordingly, the established

tolerances for livestock comm odities remain adequate and no revisions to these values are needed.

Sweet corn is the only proposed crop to which plant back intervals (PBIs) apply. The Liberty Herbicide label indicates that plant rotation to other crops after treatment of sweet corn can occur with a PBI of 120 days with the exception of small cereal grains, for which a PBI of 70 days is

allowed. Based on the results from the confine d and field rotational studies, HED concludes that the proposed rotational crop restrictions are appropriate for sweet corn.

5 .3 Water Residue Profile

The following information was provided by EFED (D 372624, C. Peck, 22

- JUN

- 2010 ; D368799, C. Peck, 07

- JUL

- 2010 ; D381992, C. Peck, 20

- OCT

- 2010 ; and D387412, C. Peck, 30

- MAY

2012 ).

Environmental Fate Assessment: E nvironmental fate studies indicate glufosinate

- ammonium is relatively stable and is very mobile (K d = 1.5; K
oc = 173; water solubility 1370 g/liter). It dissipated with a first order half

- life ranging from 4.3

– 10.3 days on bare ground and 8

– 30 days on cropped fields following a single application. The main degradation pathway in water and soil

is via microbia l action, metabolizing primarily to CO 2 , HOE 061517 [MPP] , 2

- methylphosphinico acetic acid (HOE 064619), and 2

- acetamido

- 4

- methylphosphinico

- butanoic acid. Aerobic soil metabolism produced a half

- life of approximately 4

– 23 days; metabolite concentration s peaked at 3 weeks and then began to decline. Anaerobic soil metabolism produced a half

- life of 56 days. The aerobic aquatic metabolism half

- life was 64 days in gravel pit water sand sediment.

Glufosinate may leach to ground water under certain conditi ons (such as in areas of sandy soils with high permeability and shallow ground water). Degradates HOE 061517 (K d = 0.7 and K
oc = 84) and N

- acetyl

- glufosinate (K d = 0.8) are more mobile than the parent, and may also be expected to leach to ground water. Ho wever, the potential for degradate HOE 064619 to leach to ground water is much lower because of its higher adsorption coefficient (K d = 24).

Ground and Surface Water Estimated Drinking Water Concentrations (EDW Cs ) : EFED estimated acute EDWCs for glufosina te

- ammonium and MPP using the refined Tier I Rice Model and Pesticide Flooded Application Model (PFAM) [version 0.70] without the index reservoir. T o estimate chronic EDWCs , th e acute concentrations from PFAM without the index reservoir were

assum ed to de grade over a 365

- day period, using aerobic aquatic degradation half

- lives ; thus allowing calculation of average concentration s over a one

- year period. T his method results in

chronic values a pproximately 76% and 3% lower than the acute values for glufosinate

- ammonium and MPP, respectively.

Previous analyses from EFED demonstrated that the maximum acute and chronic EDWCs for glufosinate ammonium arise from the rice uses; these values being nearly an order of magni tude higher than the values from any other crop use of glufosinate ammonium (DP 3 72624

, C

. Peck

, 6/22/2010 & DP 3 81992

, C

. Peck

, 10/20/2010). Thus, EFED conducted a comprehensive refinement of the drinking water assessment for the rice use of glufosinate ammonium, with the expectation that the resulting values should be protective of other uses.

Table 5

. 3 summarizes the PFAM EDWCs for glufosinate ammonium and MPP based on the ricePage 18 of 45

use patterns, as provided by EFED. Most of the application scenarios res ult in lower values for MPP than for glufosinate ammonium, although the maximum chronic EDWC for MPP is approximately 2x higher than the corresponding value for glufosinate ammonium : 177 and 95 ppb, respectively . Because glufosinate ammonium is considera bly more toxic than MPP, and these compounds have sufficient differences in toxicity that precludes aggregation, glufosinate

ammonium EDWCs are protective of MPP EDWCs. Accordingly, for purposes of acute and chronic dietary analyses , the recommended glufo sinate ammonium EDWCs are 390 and 95 ppb, respectively.

Table 5 .3. EDWCs for glufosinate

- ammonium and MPP from rice use derived using PFAM (maximum values appear in bold). Use rate, Number of apps, retreatment interval, water holding period

, application timing Acute EDWC ( μg/L ) Chronic EDWC 1

( μg/L )

4” 8” 4” 8”

Glufosinate

- ammonium 1.46 lbs ai/acre, 1, NA, 7 days, dry 173 86 42 21 0.73 lbs ai/acre, 2, 10, 30, dry and flooded 2 NA 320 NA 78 0.73 lbs ai/acre, 2, 10, 55, dry and flooded 2 390 NA 95 NA 0.89 lbs ai/acre, 1, NA, 7 days, dry 106 53 26 13 0.66 lbs ai/acre, 1, NA, 7 days, dry 74 38 18 9

0. 44 lbs ai/acre, 2, 10 days, 7 days, dry 88 45 22 11 0.44 lbs ai/acre, 2, 10 days, 7 days, flooded NA 375 NA 92

MPP 1.46 lbs ai/acre, 1, NA, 7 days, dry 5.7 2.9 5.5 2.8 0.73 lbs ai/acre, 2, 10, 30, dry and flooded 2 NA 88 NA 85 0.73 lbs ai/acre, 2, 10, 55, dry and flooded 2 183 NA 177 NA 0.89 lbs ai/acre, 1, NA, 7 days, dry 3.5 1.8 3.4 1.7 0.66 lbs ai/acre, 1, NA, 7 days, dry 2.2 1.1 2.1 1.1

0. 44 lbs ai/acre, 2, 10 days, 7 days, dry 3.0 1.5 2.9 1.5 0.44 lbs ai/acre, 2, 10 days, 7 days, flooded NA 45 NA 44

1. Chronic EDWC calculated by taking acute EDWC and allowing it to degrade for 365 days, using the aerobic aquatic degradation half

- life, and then taking the average value over the 365

- day period.

2. For this scenario the first application is made to a dry field, while the second application is made to a flooded field.

NA

– not allowed.

5

. 4 . Dietary Risk Assessment

Acute and chronic diet ary (food + drinking water) exposure analyse s for glufosinate ammonium

were conducted by HED ( D 402741

, W. Donovan

, 19

- JUN

- 2012 ). Glufosinate ammonium acute and chronic dietary exposure assessments were conducted using the Dietary Exposure Evaluation Model software with the Food Commodity Intake Database DEEM

- FCIDTM, Version 3.10, which incorporates consumption data from USDA’s Nation al Health a nd Nutrition Examination Survey /“What We Eat in America” (NHANES/WWEIA) dietary survey conducted in 2003

- 2008

. The 2003

- 2008 data are based on the reported consumption of individuals over two non

consecutive survey days.

5 .4 .1 Acute Dietary Exposure/RiskPage 19 of 45

Residue Data Used for Acute Assessment: Established and recommended t olerance level residues were used for the acute analysis, along with default processing factors, and 100% crop treated assumptions (unrefined analysis).

Results of Acut e Dietary Exposure Analysis : An unrefined acute dietary risk assessment for glufosinate ammonium at the EDWC of 390 ppb showed that acute dietary risk estimates are below HED’s level of concern (i.e. < 100% a PAD) for the relevant population subgr o up, females

13

- 49 years old (39 % aPAD).

5

. 4 .2 Chronic Dietary Exposure/Risk

The chronic dietary exposure assessment for glufosinate ammonium is refined using anticipated

residues based on average residue levels from field trial studies

. Average %CT inform ation and processing factors, where available, were used in the assessment. There were no PDP monitoring

data available for glufosinate ammonium

.

Results of Chronic Dietary Exposure Analysis : T he chronic dietary risk assessment for glufosinate ammonium at an EDWC of 9 5 ppb showed that chronic dietary risk estimates are below HED’s level of concern (i.e. < 100% cPAD) for all population subgroups, with the highest exposed population subgroup [all infants (<1 year old)] at 98 % of the cPAD

, and the U.S. Popu lation at 39 % of the cPAD.

The results of the dietary exposure analys e s are reported in Tables 5 .4.2

.

T able 5 .4.2

. Summary of Dietary Exposure and Risk for Glufosinate Ammonium [Acute EDWC of 390 ppb, Chronic EDWC of 95 ppb]

.

Population Subgroup 1 DEEM Acute Dietary Analysis,

95 th Percentile DEEM Chronic Dietary Analysis

Exposure (mg/kg/day) % aPAD Exposure (mg/kg/day) % cPAD

General U.S. Population

NA 2 NA 2 0.002324 39

All Infants (< 1 year old) 0.005887 98

Children 1

- 2 years old 0.004387 73

Children 3

- 5 years old 0.003447 57

Children 6

- 12 years old 0.002261 38

Youth 13

- 19 years old 0.001706 28

Adults 20

- 49 years old 0.002203 37

Adults 50

- 99 years old 0.002202 37

Females 13

- 49 years old 0.024401 39 0.002195 37

1 Values for the population with the highest risk for each type of risk assessment are bolded

. 2 NA = Not Applicable

5

. 4

. 3 Anticipated Residue and Percent Crop Treated (%CT) Information

The DEEM

- FCID chronic analysis was performed using anticipated re sidues ( ARs ) from fieldPage 20 of 45

trial data, processing factors and updated %CT information. The DEEM default processing

factors were used for all commodities except apple juice, pear juice, grape juice, and raisins, for which factors derived from the processing s tudies were used.

Percent Crop Treated : One hundred percent crop treated values were used for all proposed new

uses. The following average percent crop treated estimates (BEAD SLUA, 19

- MAR

- 2012) were used in the chronic dietary analysis for crops that are currently registered for glufosinate ammonium: almond: 15%; blueberry: 5%; field corn, 5%; grape, 15%; pecan, 1%; potato, 10%; soybean, 1%; walnut, 10%; canola, 25%; cotton, 5%; filbert, 10%; pistachio, 20%; and rice, 1%.

6.0 Residential (Non

- O ccupational) Exposure/Risk Characterization

Glufosinate ammonium is not a restricted use pesticide (RUP). There are no proposed residential

uses associated with this petition ; however, there are existing residential turf use s that have been

reassessed in this document to reflect updates to HED’s 2012 Residential SOPs along with policy changes for body weight assumptions. The revision of residential exposures will impact the human health aggregate risk assessment for glufosinate ammonium.

The quantitativ e exposure/risk assessment developed for residential handlers is based on the following exposure scenarios:

1. mixing/loading/applying liquids with a manually pressurized handgun,

2. mixing/loading/applying liquids with a hose

- end sprayer,

3. mixing/loading/apply ing liquids with a backpack sprayer, and

4. mixing/loading/applying liquids with a sprinkler can.

Data and Assumptions for Residential Handler Exposure Scenarios

Unit Exposures and Area /Amount Treated Unit exposure values and estimates for area treated were taken from HED ’s 201 2 Residential

SOPs: Lawns/Turf

. It was assumed that residential handlers would treat a maximum of 1000 ft 2

(0.023 acres).

Applicatio n Rate A maximum single application rate of 1.36 lb ai/Acre (4 fl. oz./ 1000 ft 2 ) was used for all spot treatment scenarios (EPA Reg. No. 432

- 1229).

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; t he average male adult body weight of 8 0 kg was used for estimating short

- term inhalation dose

.

Absorption Factor s A dermal absorption factor of 9% is used to estima te short

- term dermal exposure since the point of departure is based on an oral study

. A route

- specific st udy was used for the inhalation assessment

.

6.1 Residential Handler ExposurePage 21 of 45

Residential h andler exposure is expected to be short

- term

. Intermediate

- term exposures are not likely because of the intermittent nature of applications by homeowners. Summaries of the short

term dermal and inhalation risk estimate s for residential handlers are included in Table 4

. 5. The maximum application rate for each exposure scenario is present ed as the worst case scenario.

All dermal scenarios for residential ha ndlers performing spot treatment applications utilizing

hose

- end

- sprayer and sprinkler can, resulted in MOEs greater than the LOC (i.e., MOEs ≥ 1,000) and, therefore are not of concern

.

All inhalation scenarios for residential handlers resulted in MOEs g reater than the LOC (i.e., MOEs ≥ 300) and, therefore are not of concern. In this assessment, since the P O Ds selected for both dermal and inhalation routes of exposure are based on different endpoints; the MOEs for the dermal and inhalation exposure route s were not combined.

Table 6.1 Updated Summary of Short

- Term Residential Handler Exposures and Risks Estimates for

Application of Glufosinate

- Ammonium on Residential Turf.

Exposure

Scenario Application

Rate a Area

Treated Daily b Unit Exposure c Dose d MOE e

Dermal Inhal ation Dermal Inhalation

lb ai per 1000 ft2 mg/lb ai mg/kg/day Dermal Inhalation

Spot Treatments

Hose

- end Sprayer 0.0312 1000

ft 2 13.4 0.022 0.0005 0.000009 26000 1,500,000

Manually

pressurized

handwand 0.0312 1000

ft 2 63 0.018 0.0026 0.000007 5400 1,800,000

Sprinkler

can 0.0312 1000

ft 2 13.4 0.022 0.0005 0.000009 26000 1,500,000

Backpack Sprayer 0.0312 1000

ft 2 130 0.14 0.0053 f 0.0001 2600 230,000

a Application Rates based on maximum application rates of registered residential turf uses for glufosinate ammonium 4 fl oz per gallon of water to treat to treat 1000 ft 2

. b Based on HED’s SOPs: Lawns/Turf (January 2012). Area treated daily: 0.023 A = 1000 ft 2

.

c Residential Handler Attire: no gloves, short pants, short

- sleeved shirt, no respirator.

d Dose (mg/kg/day) = d aily unit exposure (mg/ lb ai) × application rate (lb ai/ A ) × area treated (Acres/day) × absorption factor (%)

÷ body weight ( 69 kg for dermal; 80 kg for inhalation ). Dermal absorption factor = 9%.

e Dermal MOE = LOAEL (14 mg/kg/day) / dermal daily dose (mg/ kg/ day), where LOC = 1000 Inhalation MOE = LOAEL (12.5 mg/kg/day) / inhalation daily dose (mg/ kg/ day), where LOC = 300

f Residential exposure estimate recommended for use in aggregate assessment.

6.2 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 dermal assessments are not performed for spot treatment uses (H ED’s SOPs: Lawns/Turf; January 2012). These types of uses can result in residues on turf but residential exposure is expected to be low.

Likewise, p ost

- application inhalation exposure while engaged in activities on or around previously treated turf is ge nerally not assessed. The combination of low vapor pressure for chemicals typically used as active ingredients in outdoor residential pesticide products andPage 22 of 45

dilution in outdoor air is likely to result in minimal inhalation exposure. Therefore, a quantita tive

post

- application inhalation exposure assessment was not performed for glufosinate ammonium at this time primarily because it has very low vapor pressure (vapor pressure less than 1 x 10 - 8
mmHg)

. 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/scipoly/SAP/me et ings/2009/120109me et ing.htm l ) 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 assessmen ts. 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 r esult in high MOEs, ranging from approximately 230,000 to 1,8 00,000.

6. 3 Spray Drift

Spray drift is always 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 groundboom application method s additionally employed for glufosinate ammonium. The Agency has been working with the Spray Drift Task Force, EPA Regional Offices

, and State Lead Age ncies for pesticide regulation and other parties to develop the best spray drift management practices. The Agency is now requiring interim mitigation measures for aerial applications that must be placed on product labels/labeling. The Agency has compl et e d its evaluation of the new data base submitted by the Spray Drift Task Force, a membership of U.S. pesticide registrants, and is developing a policy on how to appropriately apply the data and the AgDRIFT computer model to its risk assessments for pesticid es applied by air, orchard airblast

, and ground hydraulic m et hods. After the policy is in place, the Agency may impose further refinements in spray drift management practices to reduce off

- targ et drift and risk

estimates associated with aerial as well as other application types where appropriate.

Although a quantitative residential post

- application inhalation exposure assessment was not performed as a result of pesticide drift from neighboring treated agricultural fields, an inhalation

exposure assessme nt was conducted for residential handlers use on turf . This exposure scenario is representative of a worse case inhalation (drift) exposure and may be considered protective of most outdoor agricultural and commercial post

- application inhalation exposure s cenarios

.

7 .0 A ggregate Exposure/ R isk C haracterization

In accordance with the FQPA, HED must consider and aggregate glufosinate ammonium pesticide exposures and risks from three major sources: food, drinking water, and residential exposures. In an aggregate assessment, exposures from relevant sources are added together and compared to quantitative estimates of hazard (e.g., a NOAEL or PAD ), or the risks themselves can be aggregated. When aggregating exposures and risks from various sources, HED has considered both the route and duration of exposure.

7 .1 Acute Aggregate RiskPage 23 of 45

The acute dietary assessment included food and water exposures for females 13

- 49 years old and represents the acute aggregate risk assessment for glufosi nate ammonium (see Section 5 .4.1 ).

7 .2 Short

- Term Aggregate Risk

The short

- term aggregate risk assessment takes into account average exposure estimates from dietary consumption of glufosinate ammonium (food and drinking water) and residential/ non

occupational exposures. HED uses average (chronic) food and water exposure estimates when conducting short

- term aggregate exposure assessments. Short

- term expo sure has been defined as

from 1

- 30 days and HED has concluded that average exposures to food and water will more accurately reflect actual exposure over these time periods than will high end exposures. The refined chronic dietary assessment incorporated percent crop treated information for several crops

and assumed average residues levels from field trials . For livestock commodities, anticipated

residues were also assumed. The residential handler dermal and inhalation exposure estimates

were conducted using residential SOPs and ORETF data. The resulting exposures were less than

HED’ s level of concern (see Table 4.5 ) for all scenarios , with the backpack sprayer scenario giving the highest potential exposure.

Short

- term aggregate exposure to glufosina te ammonium is provided in Table 7 .2

. For average dietary exposure, the General U.S. Population was selected as it is protective for all other population subgroups except for infants and young children, who will not be applying glufosinate

ammonium. For residential/non

- occupational exposures, only the dermal route of exposure was included in the aggregate analysis since potential dermal exposures are higher than potential inhalation exposures (see Table 6.1) ; it is not appropriate to aggregate the dermal and inhalation

exposure s since the toxicity endpoints are different

. T he backpack sprayer residential exposure scenario was chosen for aggregate analysis because it is protective for the other residential exposure scenarios. The point of departure (POD) selected for short

- term aggregate exposure to glufosinate ammonium is 14 m g/kg/day. Based on these assumptions, t he estimated short

- term
aggregate MOE of 18 00 (LOC = 1000) is not of concern to HED.

Table 7 .2. Short

- Term Aggregate Risk for Glufosinate Ammonium (backpack sprayer scenario for residential mixer/loader/applicator)

Population L OAEL

(mg/kg/day) F ood + Drinking

W ater Exposure (mg/kg/day) Dermal Dose

(mg/kg/day) Total Exposure

(mg/kg/day) LOC MOE Agg

General

U.S. Population 14 0.002324 0.0053 0.00762 1000 1800

LOC=Level of Concern

MOE= L OAEL

/Exposure

MOE Aggregate = L OAEL/(E xposure food and water + E xposure dermal )

Food + Drinkin g Water exposure: See Table 5 .4.2. Dermal exposure: See Table 6.1

.

7 .3 Intermediate/Long

- Term Aggregate Risk

Intermediate/long

- term exposures are not anticipated. Therefore an intermediate /long

- term aggregate risk assessment was not performed.Page 24 of 45

7 .4 Chronic Aggregate Risk

The chronic dietary assessment included food and water exposures and represents the chronic aggregate risk assessment for glufosinate ammonium (see Section 5.4.2).

8 .0 C umulative Exposure/Risk Characterization

Unlike other pesticides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity, EPA h as not made a common mechanism of toxicity finding as to glufosinate

ammonium and any other substances

, and glufosinate ammonium does not appear to produce a toxic metabolite produced by other substances. For the purposes of this tolerance action, therefo re, EPA

has not assumed that glufosinate ammonium has a common mechanism of toxicity with other substances. For information regarding EPA’s efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of s uch chemicals, see the policy statements released by EPA’s Office of Pesticide Programs concerning common mechanism determinations and procedures for cumulating effects from substances found to have a common

mechanism on EPA’s website at http://www.epa.gov/pesticides/cumulative/.

9 .0 O ccupational Exposure/Risk Characterization

9 .1 Occupational Handler

Occupational exposure to glufosinate ammonium is anticipated for handlers who apply the formulated products to the proposed new use sites. Based on application rate and label information, dermal and inhalation exposure is expected to occur for short

- and intermediate

- term durations. Chronic exposure is not expected for the proposed use patterns. Potential occupational exposure scenarios include:

1) M ixer/ L oader using open pouring of liquids in support of aerial, groundboom, and spot/ directed spray application operations;

2) A erial A pplicators (enclosed cockpit);

3) A pplicators u sing open

- cab ground boom equipment;

4) F laggers in support of aerial applica tions; and

5) Mixer/Loader/ Applicator (MLAP) for mechanically pressurized handgun spray applications.

6) Mixer/Loader/ Applicator (MLAP) for Backpack s prayer applications.

Chemical

- specific data were not submitted to the Agency in support of this Section 3 registration

. 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 o f chemical

- specific data, include the Pesticide Handlers Exposure Database Version 1.1 (PHED 1.1), the Agricultural Handler Exposu re Task Force (AHETF) database , or other registrant

- submitted occupational exposure studies. Some of these data are proprieta ry ( e.g., AHETF data), and subject to the data protection provisions of FIFRA. The standard values recommended for use in predicting handler exposure that are used in this assessment, known as “unit exposures”, are outlined in the “OccupationalPage 25 of 45

Pesticide 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

.

The average adult weight of 80 kg was used for estimating inhalation exposure

. For dermal risk

assessments , a 6 9 kg body weight was used to calculate exposure to glufosinate ammonium s ince

the point of departure was selected from a developmental toxicity study

. A dermal absorption factor of 9% was applied during the conduct of the short

- and intermediate

- term dermal exposure assessments, based on a dermal penetration study ( D289836, B. Daiss, 17

- JUN

- 2003 )

. For

inhalation risk assessment, a route specific study was used

.

In this assessment

, s ince the Points of Departure ( P O Ds ) selected for both short

- and

int ermediate

- term dermal and inhalation routes of exposure are based on different endpoints and

the toxicological effects are different ; the MOEs for the dermal and inhalation exposure routes

were not combined

.

Daily dermal or inhalation handler exposures are estimated for each applicable handler task with the application rate, the area treated in a day, and the applicable dermal or inhalation unit exposure using the following formula:

Daily Exposure (mg ai/day) = Unit Exposure (mg ai/lb ai handled) x Appl ication Rate (lbs ai/area) x Daily Area Treated (area/day)

Where:

Daily Exposure = Amount (mg ai/day) deposited on the surface of the skin that is available for dermal absorption or amount inhaled that is available for inhalation absorptio n; Unit Exposure = Unit exposure value (mg ai/lb ai) Application Rate = Normalized application rate based on a logical unit treatment, such as acres; and Daily Area Treated = Normalized application area based on a logical unit

tre atment such as acres (A/day).

The daily dermal or inhalation dose is calculated by normalizing the daily exposure by body weight and adjusting, if necessary, with an appropriate dermal or inhalation absorption factor using the following formula:

Average Daily Dose (mg/kg/day) = Daily Exposure (mg ai/day) x (Absorption Factor (%/100)) / Body Weight (kg)

Where:

Average Daily Dose = Absorbed dose received from exposure to a pesticide in a given scenario (mg ai/kg body weight/day); Daily Exposure = Amoun t (mg ai/day) deposited on the surface of the skin that is available for dermal absorption or amount inhaled that is available for inhalation absorption; Absorption Factor = A measure of the amount of chemical that crosses aPage 26 of 45 biological boundary such as the skin or lungs (% of the total available absorbed); and Body Weight = Body weight determined to represent the population of interest in a risk assessment (kg).

Non

- cancer dermal and inhalation risks for each applicable handler scenario are calculated using a MOE, which is a ratio of the point of departure (POD) to the daily dose. All MOE values were calculated using the formula below:

MOE= POD (mg/kg/day) / Ave rage Daily Dose (mg/kg/day)

See Table s 9 .1a

- 9 .1c for a summary of estimated exposures and risks. Results from the assessment of all occupational handler scenarios

, with the exception of mixer/loader/applicator (MLAP) spot treatments scenarios with mech anically pressurized handgun, indicate that short

and intermediate

- term dermal risks are not of concern to the Agency (i.e., MOE s ≥ 1000) at level of personal protection recommended on the label ( i.e., gloves). S hort

- and intermediate

- term
dermal risks ML AP scenarios with mechanically pressurized handgun for spot treatments on olives, citrus, pome, and stone fruit are of potential concern to the Agency ( MOE= 160 ) even with the addition of personal protection to mitigate exposure such as an extra layer of clothing (coveralls) and gloves

.

Likewise, results from the assessment of all occupational handler scenarios, with the exception of MLAP spot treatments scenarios with mechanically pressurized handgun, indicate that short

- and

intermediate

- term inhalatio n risks are not of concern to the Agency ( i.e ., MOEs ≥ 300) at baseline level of personal protection (i.e. no respirator). MLAP scenarios, for spot treatments on olives, citrus, pome, and stone fruit, result in short

- and intermediate

- term dermal risks of potential concern to the Agency ( MOE= 82 ) even with the addition of a PF10R respirator.

The formulated end use products labels involved in this assessment indicate user restrictions and

state : “ for retail sale to and use only by certified applicators or persons under their supervision and only for the uses covered by the certified applicator’s certification”. The proposed glufosinate ammonium label s direct applicators and other handlers who might be exposed to the diluted chemical and anything t hat has b een treated, such as plants, soil, or water to wear specific personal protection equipment (PPE). Handlers mixing

, loading

, and cleaning equipment are instructed to wear a chemical resistant apron

. Applicators and other handlers must wear coveralls; chem ical resistant gloves and footwear, plus socks, and protective eyewear (goggles, face shield or safety glasses). Mixers and loaders supporting aerial applications must wear a dust

mist filtering respirator (MSHAINIOSH approval number prefix TG21 C), or a N I OSH approved respirator with any N, R, P or HE filter

. PPE required for early entry to treated areas that is permitted under the Worker Protection Standard must be used.

The minimum level of PPE for handlers is based on acute toxicity for the end

- use p roduct. The Registration Division (RD) is responsible for ensuring that PPE listed on the label is in compliance with the Worker Protection Standard (WPS) for agricultural pesticides.Page 27 of 45

Table 9 .1a Short

- /Intermediate Term Agricultural Handler Exposure and Risk Estimates for Glufosinate A mmonium

Exposure

Scenario Crop or Target App

Rate a (lb ai/A) Acres

Treated Daily b Unit Exposure c Dose (mg/kg/Day) MOEs

(Dermal LOC = 1000 Inhalation LOC = 300)

Baseline

Dermal (mg/lb ai) PPE

Dermal (mg/lb ai) I nhalation

(ug/lb ai) Baseline

Dermal d,h PPE

Dermal i Inhalation e Baseline

Dermal f PPE

Dermal Inhalation g ,i

Mixer/Loader

Mixing/Loading to Support

Aerial treatments (PHED) Sweet

Corn 0.365 350 0.220 0.0376 (SL/G) 0. 219 0.0367 0.00626 (SL/G)

0.00485 (DL/G) 0.00035 380 2,200 (SL/G) 36,000

Mixing/Loading to Support Groundboom Applications (PHED) Sweet

Corn 0.365 80 0.220 0.0376 (SL/G) 0.219 0.00837 0.00143 (SL/G) 0.000079 1,700 9,800 (SL/G) 160,000

Citrus Fruit,

Pome Fruit,

Stone Fruit,

Olives 1.50 80 0.220 0.0376 (SL/G) 0.219 0.0344 0.00588 (SL/G) 0.000329 410 2,400 (SL/G) 38,000

a) Application Rates based on proposed uses on label for Glufosinate

- ammonium formulations Liberty Herbicide (EPA Reg. No. 264

- 660) and Liberty 280 SL Herbicide (EPA Reg. No. 264

- 829). Units expressed in lb ai/Acre unless specified otherwise. b) Exposure Science Advisory Council Policy # 9.1 c) Unit Exposures based on Unit Exposures based on “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (PHED) ( http://www.epa.gov/pesticides/science/handler

- exposure

- table.pdf ), dated September 2011. Engineering control unit exposure for applying sprays via aerial equipment = enclosed cock pit. d) Dermal Dose (mg/kg/day) = daily unit exposure (mg/ lb ai) x application rate (lb ai/acre) x acres treated x dermal absorption factor (9%) / body weight (69 kg adult female). e) Inhalation Dose (mg/kg/day) = daily unit exposure (μg/ lb ai) x conversio n factor (1 mg/1,000 μg) x application ra te (lb ai/acre) x acres treated / body weight (80 kg). f) Dermal MOE = LOAEL (14 mg/kg/day) / dermal daily dose (mg/ kg/ day). Level of concern = 1000. g) Inhalation MOE = LOAEL (12.5) mg/kg/day) / inhalation daily dos e (mg/ kg/ day). Level of concern = 300. h) Baseline Dermal: Long

- sleeve shirt, long pants, and no gloves; i) Baseline Inhalation: no respirator j) PPE: G ( gloves ), SL ( Single Layer ), DL (Double Layer), PF10 R (respirator) , E.C. (Engineering Control; Closed System ).Page 28 of 45

Table 9 .1b Short

- /Intermediate Term Agricultural Handler Exposure and Risk Estimates for Glufosinate A mmonium

Exposure

Scenario Crop or Target App

Rate a (lb ai/A) Acres

Treated Daily b Unit Exposure c Dose (mg/kg/Day) MOEs

(Dermal LOC = 1000 Inhalation LOC = 300)

Baseline

Dermal h
(mg/lb ai) PPE

Dermal j, g
(mg/lb ai) I nhalation g

(ug/lb ai) Baseline

Dermal d,h PPE

- G

Dermal Inhalation e Baseline

Dermal f, h PPE

- G

Dermal Inhalation i

Applicator

Applying Sprays

via Aerial Equipment

– Enclosed Cockpit (PHED) Sweet Corn 0.365 350 No Data 0.005 (EC) 0.068

(EC) No Data 0.000833 (EC) 0.000109

(EC) No Data 17,000 (EC) 110,000

(EC)

Applying Sprays

via Groundboom Equipment Open

Cab Sweet Corn 0.365 80 0.0786 0.0161 (SL/G) 0.34 0.003 0.000613 (SL/G) 0.000124 4,700 23,000 (G) 100,00

Citrus Fruit, Pome Fruit, Stone Fruit,

Olives 1.5 80 0.0786 0.0161 (SL/G) 0.34 0.0123 0.00252 (SL/G) 0.00057 1,100 5,600 (G) 25,000

Flagger

Flagging for Aerial Sprays Sweet Corn 0.365 350 0.011 0.012 0.35 .00183 0.0020 0.00064 7,600 7,000 (G) 19,000

a) Application Rates based on proposed uses on label for Glufosinate

- ammonium formulations Liberty Herbicide (EPA Reg. No. 264

- 660) and Liberty 280 SL Herbicide (EPA Reg. No. 264

- 829). Units expressed in lb ai/Acre unless specified otherwise. b) Exposure Science Advisory Council Policy # 9.1 c) Unit Exposures based on Unit Exposures based on “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (PHED) ( http://www.epa.gov/pesticides/science/handler

- exposure

- table.pdf ), dated September 2011. Engineering control unit exposure for applying sprays via aerial equipment = enclosed cockpit. d) Dermal Dose (mg/kg/day) = daily unit exposure (mg/ lb ai) x applicati on rate (lb ai/acre) x acres treated x dermal absorption factor (9%) / body weight (69 kg adult female). e) Inhalation Dose (mg/kg/day) = daily unit exposure (μg/ lb ai) x conversion factor (1 mg/1,000 μg) x application ra te (lb ai/acre) x acres treated / bo dy weight (80 kg). f) Dermal MOE = LOAEL (14 mg/kg/day) / dermal daily dose (mg/ kg/ day). Level of concern = 1000. g) Inhalation MOE = LOAEL (12.5) mg/kg/day) / inhalation daily dose (mg/ kg/ day). Level of concern = 300. h) Baseline Dermal: Long

- sleeve shirt, long pants, and no gloves; i) Baseline Inhalation: no respirator j) PPE: G ( gloves ), SL ( Single Layer ), DL (Double Layer), PF10 R (respirator) , E.C. (Engineering Control; Closed System).Page 29 of 45

Table 9 .1c Short

- /Intermediate Term Agricultural Handler Exposure and R isk Estimates for Glufosinate A mmonium (Spot/Directed Spray Applications)

Exposure

Scenario App

Rate a (lb

ai/ gal ) Acres

Treated Daily b Unit Exposure c , j Dose (mg/kg/Day) MOEs

(Dermal LOC = 1000 Inhalation LOC = 300)

Baseline

Dermal h (mg/lb ai) PPE

Dermal j
(mg/lb ai) I nhalation

(ug/lb ai) Baseline

Dermal d,h PPE

Dermal

j Inhalation e Baseline

Dermal f,h PPE Dermal j Inhalation g ,i

Citrus Fruit, Pome Fruit, Stone Fruit, Olives

Mixer/Loader/Applicator

Mixing/Loading/Applying (MLAP) with Mechanically Pressurized Handgun ( spot/ directed spray ) 1.7 fl oz/gal

0.031 lbai/gal 1,000

gallons 4.310 2.160 (DL/G) 3931

(No respirator)

393.1 (PF10R) 0.175 0.0874 (DL/G) 0.0004

0.153 (PF10R) 80 160 (DL/G) 8.2

82 (PF10R)

Mixing/Loading/Applying (MLAP) with Backpack Sprayer ( spot/ directed spray ) 40 gallons 8.260 8.260 2.58 0.0133 0.0133 0.0004 1,100 1,100 (SL/G) 310,000

a) Application Rates based on proposed uses on label for Glufosinate

- ammonium formulations Liberty Herbicide (EPA Reg. No. 264

- 660) and Liberty 280 SL Herbicide (EPA Reg. No. 264

- 829). Units expressed in lb ai/Acre unless specified otherwise. b) Exposure Science Advisory Council Policy # 9.1 c) Unit Exposures based on Unit Exposures based on “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (PHED) ( http://www.epa.gov/pesticides/science/handler

- exposure

- table.pdf ), dated September 2011. Engineering control unit exposure for applying sprays via aerial equipment = enclosed cockpit. d) Dermal Dose (mg/kg/day) = daily unit exposure (mg/ lb ai) x applicati on rate (lb ai/acre) x acres treated x dermal absorption factor (9%) / body weight (69 kg adult female). e) Inhalation Dose (mg/kg/day) = daily unit exposure (μg/ lb ai) x conversion factor (1 mg/1,000 μg) x application ra te (lb ai/acre) x acres treated / bo dy weight (80 kg). f) Dermal MOE = LOAEL (14 mg/kg/day) / dermal daily dose (mg/ kg/ day). Level of concern = 1000. g) Inhalation MOE = LOAEL (12.5) mg/kg/day) / inhalation daily dose (mg/ kg/ day). Level of concern = 300. h) Baseline Dermal: Long

- sleeve shirt, long pants, and no gloves; i) Baseline Inhalation: no respirator j) PPE: G ( gloves ), SL ( Single Layer ), DL (Double Layer), PF10 R (respirator) , E.C. (Engineering Control; Closed System).Page 30 of 45

9 .2 Occupational Post

- A pplication Risk

Inhalation Post

-

Application Risk

Based on the Agency's current practices, a quantitative occupational post

- application inhalation exposure assessment was not performed for glufosinate ammonium

. However , there are multiple potential sources of post

- applic ation inhalation exposure to individuals performing post

- application activities in previously treated fields. These potential sources include volatilization of pesticides and resuspension of dusts and/or particulates that contain pesticides. The Agency s ought 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 ( htt p://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html ). The Agency is in the process of evaluating the SAP report as well as available post

- application inhalation exposure data generated by the Agricultural Reentry Task Force and may, as appropriate, develop policies and procedures, to identify the need for and, subsequently, the way to incorporate occupational post

- application inhalation exposure into the Agency's risk assessments. If new policies or procedures are put into place, the Ag ency may revisit the need for a quantitative occupational post

- application inhalation exposure assessment for glufosinate

ammonium

. Although a quantitative occupational post

- application inhalation exposure assessment was not performed, an inhalation expos ure assessment was performed for occupational/commercial handlers. Handler exposure resulting from mixing/loading pesticides is likely to result in higher exposure than post

application exposure. Thus , handler inhalation exposure estimates would be prote ctive of most occupational post

- application inhalation exposure scenarios.

Dermal Post

-

Application Risk

A quantitative post

- application dermal exposure assessment was not performed for glufosinate ammonium

uses on citrus fruit , pome fruit, stone fruit, and olives

. There is a low potential for occupational post

application exposure associated with the use of ground and spot

- directed application of herbicides

. Most of the proposed uses for glufosinate ammonium are ground

- directed uses where crop foliage treat ment
should be avoided . Currently, HED has no transfer coefficients (TCs) or other data to assess post

application dermal exposures to soil by occupational workers. Therefore, for the proposed soil

- directed

uses, post

- application exposures and risks to occupational workers were not quantitatively assessed for these crops. In general, such exposures are considered to be minimal

.

Even though the proposed uses for glufosinate ammonium are for post

- emergent applications when crop foliage is present, dislodgeable foliar residues are expected to be very low during post

- application

activities since the proposed label advises applicators to avoid contact of Liberty® 280 SL Herbicide with foliage or parts of trees, other than mature brown bark as serious i njury may occur. The label specifies a preharvest interval of 14 days for citrus fruit , pome fruit, stone fruit, and olive crops.

There is potential for p ost

- application dermal exposure to glufosinate ammonium followin g the proposed

use on sweet corn

. Occupational re

- entry workers may experience short

- /intermediate

- term exposure to glufosinate ammonium while performing post

- application activities such as scouting and irrigati on of

sweet corn

. Post

- application exposure resulting from detasseling activit ies was not assessed since it is estimated that this activity would occur too late after the last application permitted for the herbicide (ExpoSAC meeting August 5, 2010). T here fore, post

- application dermal exposure scenarios for the proposed new uses of glufosinate ammonium on sweet corn were assessed for scouting and irrigati on activities only

. The post

- application activity scenarios along with respective TCs and risk estimates for

short

- /intermediate

- term MOEs are summarized in Table 9 .2

.Page 31 of 45

It is the policy of HED to use the best available data to assess post

- application exposure.

Since no chemical

- specific dislodgeable foliar residue (DFR) data were submitted in support of this registration action, dermal transfer coefficients (TCs) were used to rel ate foliage residue values to activity patterns (e.g., scouting) to estimate potential human exposure. Sources of generic post

- application data, used as surrogate data in the absence of chemical

- specific data, are derived from Agricultural Reentry

Task Fo rce (ARTF) exposure monitoring studies, and, as proprietary data, are subject to the data protection provisions of FIFRA. The standard values recommended for use in predicting post

- application exposure that are used in this assessment, kno wn as “transfer coefficients”, are presented in the “Science Advisory Council for Exposure (ExpoSAC) Policy 3” ( http://www.epa.gov/pesticides/science/exposac_policy3.pdf ), which, along with additional information about the ARTF data, can be found at http://www.epa.gov/pesticides/science/post

- app

- exposure

data.html

. It is also assumed that a f raction of ai (2 5 % of the rate of application) is available as dislodgeable foliar residue on day zero after initial treatment with a continued dissipation rate of 10% per day on following days

.

The following equations were used to calculate risks for wor kers performing post

- application activities:

Dislodgeable Foliar Residue

DFR t (μg/cm 2 ) = AR (lb ai/acre) × F × (1

- D) t × 4.54E8 μg/lb × 2.47E

- 8 acre/cm 2

Where:

DFR t = dislodgeable foliage residue on day "t" (μg/cm 2 ),

AR = application rate (lb ai/acre),

F = fraction of ai retained on foliage (unitless), and

D = fraction of residue that dissipates daily (unitless).

Daily Dose Daily dose (dermal) is calculated by normalizing the daily exposure value by body weight and accounting for absorption factors:

DD t (mg/kg

- day) = DFR t (μg/cm 2 ) × 1E

- 3 mg/μg × TC (cm 2 /hr) × DA (9%) × ET (hrs) BW (kg)

Where:

DD t = daily dermal dose on day “t,”

t = number of days after application day (days),

DFR t = dislodgeable foliage residue on day "t" (μg/cm 2 ),

TC = transfer coefficient (cm 2 /hr),

DA = dermal absorption factor (unitless),

ET = exposure time (hr/day), and

BW = body weight (kg).

Margin of Exposure (MOE) The daily dermal dose received by occupational handlers was compared to the appropriate PoD (i.e. LOAEL) to assess the risk to occupational handlers. All MOE values were calculated using the following

formula:

MOE = LOAEL (mg/kg/day)

ADD (mg/kg/day)

Where:

MOE = Margin Of E xposure (unitless),

ADD = Aver age Daily D ose (mg/kg/day) , and

LOAEL = L owest O bserved A dverse Effect L evel (mg/kg/day)Page 32 of 45

The results of the glufosinate ammonium post

- application exposure and dermal risk assessment for sweet corn indicate that an MOE of 1,200 is achieved on Day 0 for scouting mature/high foliage plants. However, for irrigation activities, an acceptable MOE of 1,050 is not achieved until Day 4; therefore, this

post

- application activity is of potential concern to the Agency. The proposed Liberty® Herbicide label

i ndicates an REI of 12 hrs; thus , this timing needs revision based upon the post

- application exposure

estimates obtained for sweet corn to achieve an MOE ≥ 1000

. The proposed label states a preharvest interval of 50 days for sweet corn. The post

- applicati on activity scenarios along with respective TCs and

risk estimates for short

- /intermediate

- term MOEs are summarized in Table 9 .2.

Table 9 .2 Summary of Estimated Post

- A pplication Risks for Glufosinate A mmonium (9 % absorption factor) Crop Maximum Application

Rate a DAT b DFR c TC d Activity d Short

- /Int

Term MOE e

Sweet

corn 0.365 0 1.024 1,100 Scouting mature/high foliage plants 1,200

0 1.024 1,900 Irrigation mature/high foliage plants 690

4 0.672 1,900 Irrigation mature/high foliage plants 1,050

a) Maximum application rate (lb ai/A) indicated on proposed labels Reg.No.279

- 3313, 279

- 3108. b) DAT = Days after treatment needed to reach the LOC of 1000; DAT 0 = the day of treatment, after sprays have dried; assumed to be approximately 12 hours. c) DFR (μg/cm 2 ) = Application rate (lb ai/A) x Fraction of ai retained on foliage on day zero (25%) × (1

- fraction of residue that dissipates daily 10%) t × 4.54E8 μg/lb × 2.47E

- 8 acre/cm 2

. d) TC (cm 2 /hr) = Transfer coefficients and associated activities from ExpoSAC Policy 3” ( http://ww w.epa.gov/pesticides/science/exposac_policy3.pdf ) e) MOE = MOE on the corresponding DAT. MOE = LOAEL / Daily Dose. Daily Dose = [DFR (μg/cm 2 ) × Transfer Coefficient × 0.001 mg/μg × 8 hrs/day × dermal absorption 9 %] body weight (69 kg adult).

The toxici ty categories of the active ingredient for acute dermal, eye irritation, and skin irritation potential are used to determine the interim REI (Restricted

- entry Intervals). The glufosinate ammonium technical material has been classified in Toxicity Category III for acute dermal and primary eye irritation. It is not a dermal irritant (toxicity category IV) nor is it a dermal sensitizer. Per the Worker Protection Standard (WPS), a 12

- hr restricted entry interval (REI) is required for chemicals classified unde r Toxicity Category

III or IV. Both labels indicate an REI of 12 hrs, which is in compliance with the WPS for most post

application activities

. However, an REI of 4 days is needed based upon the post

- application exposure

estimates obtained for sweet corn to achieve the target MOE ≥ 1000

.

10.0 R eferences

Endpoint Selection Document s Glufosinate ammonium

– 3 rd Report of the Hazard Identification Assessment Review Committee ; B. Tarplee, 4/17/2003.

Glufosinate ammonium

– Review of Developmental Neurotoxicity Study in Rats (MRID 46455701); DP#: 312684, R.J. Mitkus, 8/24/2005.Page 33 of 45

Glufosinate ammonium

– Review of 28

- Day Inhalation Toxicity Study (MRID 47058101); DP#: 337298, L. Austin, 9/6/2007.

Glufosinate ammonium

– Request to Waive Requirement for Glutamine Synthetase Measurements and Other Data Requirements; DP#: 328229, L. Austin, TXR No. 0054838, 4/8/2008.

Glufosinate ammonium

– ToxSAC Meeting on June 10, 2010 ; J. Kidwell, 6/29/2010.

Risk Assessments Glufosin ate Ammonium (PC Code 128850). Section 3 Registrations for Transgenic Cotton and Cotton (ID#

- 0F06140), Transgenic Rice (ID#

- 0F06210), and Bushberry (ID#

- 2E06404). Human Health Risk Assessment

. DP#: 290086 ; T. Bloem, PV Shah, and M. Dow, 8/7/2003

.

Glufosinate Ammonium. Human Health Risk Assessment in Support f or the Proposed New Use of Glufosinate Ammonium in/on Citrus Fruits (Crop Group 10), Pome Fruits (Crop Group 11), Stone Fruits (Crop Group 12), Olives, and Sweet Corn; DP#: 372623

, W. Donovan et. al.

, 12/15/2010.

Dietary Exposure Memorand a Glufosinate Ammonium. Update of the Revised Acute and Chronic Aggregate Dietary (Food and Drinking Water) Exposure Assessment in Support of the Petition Proposing Tolerances for Residues of Glufosinate Ammonium in/on Citrus Fruits (Crop Group 10), Pome Fruits (Crop Group 11), Stone Fruits (Crop Group 12), Olives, and Sweet Corn; DP#: 402741

, W. Donovan

, 6/19/2012.

Drinking Water Memoranda Tier II Drinking Water Assessment for Glufosinate

- ammonium on Sto ne Fruit, Citrus, Pome Fruit, and

Olives ; DP#: 372624 ; C. Peck ; 6/22/2010

.

Tier II Drinking Water Assessment for Glufosinate

- ammonium on Sweet Corn ; DP#: 3 68799 ; C. Peck ; 7/7/2010

.

Refined Drinking Water Assessment for Glufosinate

- ammonium Use on Rice; DP#: 387412; C. Peck;

5/30/2012.

Residue Chemistry Data Review Glufosinate Ammonium. Petitions for the Establishment of Permanent Tolerances in/on Citrus Fruits (Crop Group 10), Pome Fruits (Crop Group 11), Stone Fruits (Crop Group 12), Olives and Sweet Corn. Summary of Analytical Chemistry and Residue Data

. DP# : 372625 ; I. Negrón

- Encarnación ; 8/31 /2010

.

Occupational and Residential Exposure Assessment Glufosinate

-

Ammonium; Occupational and Residential Risk Assessment to Support Request for Section 3

R egistrations on Sweet Corn, Citrus Fruit, Pome Fruit, Stone Fruit, and Olives. DP#: 368798, A. Rivera

Lupiáñez , 8/31/2010.Page 34 of 45 A ppendix A

A.1 Toxicology Data Requirements
The requirements (40 CFR 158.340) for food uses of glufosinate ammonium are in Table 1. Use of the new guideline numbers does not imply that the new (1998) guideline protocols were used.

Study Technical

Required Satisfied

870.1100 Acute Oral Toxicity

................................ ....................... 870.1200 Acute Dermal Toxicity

................................ .................. 870.1300 Acute Inhalation Toxicity

................................ .............. 870.2400 Acute Eye Irritation

................................ ....................... 870.2500 Acute Dermal Irritation

................................ ................. 870.2600 Skin Sensitization

................................ .......................... yes

yes

yes

yes

yes

yes yes

yes

yes

yes

yes

yes

870.3100 90

- Day Oral Toxicity in Rodents

................................ .. 870.3150 90

- Day Oral Toxicity in Nonrodents

............................. 870.3200 21/28

- Day Dermal Toxicity

................................ .......... 870.3250 90

- Day Dermal Toxicity

................................ ............... 870.3465 90

- Day Inhalation Toxicity (28 days)

........................... Yes

Yes

yes

No

Yes Yes

See Chronic

Yes

-- Yes
870.3700a Prenatal Developmental Toxicity (rodent)

.................... 870.3700b Prenatal Developmental Toxicity (nonrodent)

.............. 870.3800 Reproduction and Fertility Effects

................................ Yes

Yes

yes Yes

Yes

Yes
870.4100a Chronic Toxicity (rodent)

................................ .............. 870.4100b Chronic Toxicity (nonrodent)

................................ ........ 870.4200a Carcinogenicity (rat)

................................ ...................... 870.4200b Carcinogenicity (mouse)

................................ ............... 870.4300 Combined Chronic Toxicity/Carcinogenicity

............... Yes.

Yes

Yes

Yes

Yes See combined.

Yes

Yes

Yes

Yes
870.5100 Mutagenicity

— Bacterial Reverse Mutation Test

.......... 870.5300 Mutagenicity

— Mammalian Cell Gene Mutation Test

.. 870.5395 Mutagenicity

— Structural Chromosomal Aberrations

.. 870.5395 Mutagenicity

– in vivo mammalian cytogenetics
870.5500 Mutagenicity

— bacterial DNA damage/repair test

........ 870.5550 Mutagenicity

– unscheduled DNA synthesis Yes

Yes

Yes

Yes

No

No Yes

Yes

Yes 1

Yes

Yes

Yes
870.6200a Acute Neurotoxicity Screening Battery (rat)

................. 870.6200b 90

- Day Neurotoxicity Screening Battery (rat)

.............. 870.6300 Developmental Neurotoxicity

................................ ....... Yes

Yes

Yes Yes

Yes 2

Yes

870.7485 Metabolism and Pharmacokinetics

................................ 870.7600 Dermal Penetration

................................ ........................ 870.7800 Immunotoxicity

................................ ............................. Yes

Yes

Yes Yes

Yes

Yes

1 Although the structural chromosome aberration study is listed as being required, it is no longer considered necessary for glufosinate ammonium because there are two additional studies (bacterial DNA damage/repair test and unscheduled DNA synthesis) and because glufosinate is classified as "not likely" to be a carcinogen in humans.

2 The submitted study was classified as unacceptable/guideline but demo nstrated neurotoxicity at high dose s. A developmental neurotoxicity study classified as acceptable set the LOAEL at a low level ; thus, a repeat of the subchronic neurotoxicity screening study is un necessary.Page 35 of 45

A.2 Toxicology Profile

Table 1: Acute Toxicity of Glufosinate ammonium Techn ical

Guideline No. Study Type MRID No. Results Toxicity Category

81

- 1 Acute Oral 00142430, 00142431,

00142432 LD 50 = 4010 mg/kg in males

LD 50 = 3030 mg/kg in females III

81

- 2 Acute Dermal 00142436, 00142437 LD 50 = >2000 mg/kg in males

& females III

81

- 3 Acute Inhalation 00151496, 00151497 LC 50 = 4.42 m/liter estimated in

males & females III

81

- 4 Primary Eye Irritation 00142438 eye irritant, corneal opacity

reversible within 72 hours III

81

- 5 Primary Skin Irritation 00142438 not a dermal irritant IV

81

- 6 Dermal Sensitization 00142439 not a dermal sensitizer N/APage 36 of 45

Table 2: Toxicity Profile of Glufosinate Ammonium Technical

Guideline No./ Study Type MRID No. (year)/

Classification /Doses Results

870.3100

90

- Day oral toxicity

rodents

- rat (range

finding study) 45179103 (2000)

Acceptable/nonguideline 0, 100 or 1000 ppm, Glufosinate 0, 6.2

- 8.8, or 64

- 90 mg/kg/day (males only) 0, 1000 or 10,000 ppm, N.acetyl

L

- glufosinate 0, 65

- 90, or 657

- 935 mg/kg/day (males only) Glufosinate ammonium

NOAEL = 6.2

- 8.8 mg/kg/day in males

LOAEL = 64

- 90 mg/kg/day in males, based on glutamine synthetase inhibition in the brains

N

- acetyl

- L

- glufosinate disodium

NOAEL = 65

- 90 mg/kg/day in males

LOAEL = 657

- 935 mg/kg/day in males, based on glutamine synthetase inhibition in the brains

870.3100

90

- Day oral toxicity

rodents

- mouse 40345609 (1986)

Acceptable/guideline 0, 80, 320 or 1,280 ppm; 0, 12, 48 or 192 mg/kg/day NOAEL = 48 mg/kg/day in males, 192 mg/kg/day in females (HDT) LOAEL = 192 mg/kg/day in males, not achieved in females; based on the changes in clinical biochemistry and liver weights in males

870.3200 Repeated

Dose Dermal Toxicity

- rat 40345605 (1985)

Acceptable/guideline 0, 100, 300 or 1000 mg/kg/day NOAEL= 100 mg/kg/day LOAEL= 300 mg/kg/day based on clinical observations (aggressive behavior, piloerection, and a high startle response)

870.3465

Subchronic

inhalation

- 28

- day repeat dosing

- rat 40345606 (1985)

Supplementary 0, 8, 20 or 46 mg/m 3

(estimated 0, 2.2, 5.5 or 12.6 mg/kg/day). NOAEL = 8 mg/m 3 (estimated 2.2 mg/kg/day) LOAEL = 20 mg/m 3 (estimated 5.5 mg/kg/day) based on clinical signs, decreased lung weight, increased body weight (female), tono

- clonic convulsions (2 males ). At the highest dose, 4 deaths.

879.3465

Subchronic

inhalation

- 28

- day repeat dosing

- rat 47058101 (2007)

Acceptable/Non

- guideline 0, 56 or 105 mg/m 3 , or an estimated 0, 12.5 or 25 mg/kg/day LOAEL = 0.56 mg/m 3 (estimated 12.5 mg/kg/day)

– lung/bro nchial congestion in females, some clinical signs (isolated and transient). Liver and kidney weights.

870.3700a

Prenatal developmental in

rodents

- rat 00142445, 00142446 (1982)

0, 0.50, 2.24 or 10 mg/kg/day

00151499, 00151500 (1982) 0, 0.50, 2.24 or 10 mg/kg/day 0, 10, 50 or 250 mg/kg/day

40345610 (1986) 0, 0.5, 2.24 or 10.0 mg/kg/day

All three studies combined Acceptable/guideline Maternal : NOAEL = 10 mg/kg/day LOAEL = 50 mg/kg/day based on vaginal bleeding and hyperactivity Developmental : NOAEL = 50 mg/kg/day LOAEL =250 mg/kg/day based on dilated renal pelvis

870.3700b Prenatal developmental in

nonrodents

- rabbit 40345611, 41144703 (1984)

Acceptable/guideline 0, 2.0, 6.3 or 20.0 mg/kg/day Maternal : NOAEL = 6.3 mg/kg/day

LOAEL = 20.0 mg/kg/day based on reduced food consumption, body weight and weight gains Developmental : NOAEL = 6.3 mg/kg/day LOAEL = 20.0 mg/kg/day based on decreased body weights and fetal death

870.3800 Reproduction and fertility effects

- rat 40345612 (1988)

Acceptable/guideline 0, 40, 120 or 360 ppm 0, 2.0, 6.0, or 18.0 mg/kg/day Parental/Systemic NOAEL = 18.0 mg/kg/day (HDT).

LOAEL = not established Reproductive NOAEL = 6.0 mg/kg/day LOAEL = 18.0 mg/kg/day based on decreased number of viable pupsPage 37 of 45

Guideline No./ Study Type MRID No. (year)/

Classification /Doses Results

Offspring NOAEL = 6.0 mg/kg/day LOAEL = 18.0 mg/kg/day based on decreased number of viable pups

870.3700b Prenatal developmental in

nonrodents

- rabbit 40345611, 41144703 (1984)

Acceptable/guideline 0, 2.0, 6.3 or 20.0 mg/kg/day Maternal : NOAEL = 6.3 mg/kg/day LOAEL = 20.0 mg/kg/day based on reduced food consumption, body weight and weight gains Developmental : NOAEL = 6.3 mg/kg/day LOAEL = 20.0 mg/kg/day based on decreased body weights and fetal death

870.3800 Reproduction and fertility effects

- rat 40345612 (1988)

Acceptable/guideline 0, 40, 120 or 360 ppm 0, 2.0, 6.0, or 18.0 mg/kg/day Parental/Systemic NOAEL = 18.0 mg/kg/day (HDT).

LOAEL = not established Reproductive NOAEL = 6.0 mg/kg/day LOAEL = 18.0 mg/kg/day based on de creased number of viable pups Offspring NOAEL = 6.0 mg/kg/day LOAEL = 18.0 mg/kg/day based on decreased number of viable pups

870.4100b Chronic toxicity

- dog 40345608 (1984)

Acceptable/guideline 0, 2.0, 5.0 or 8.5 mg/kg/day NOAEL = 5.0 mg/kg/day LOAEL = 8.5 mg/kg/day based on mortality (week 2) and alterations in the electrocardiogram at 6 months

870.4200 Carcinogenicity

- rat 44539501 (1989)

Acceptable/guideline 0, 1000, 5000 or 10000 ppm 0/0, 45.4/57.1, 228.9/281.5, or 466.3/579.3 mg/kg/day, M/F NOAEL = 45.4 mg/kg/day in males, 57.1 mg/kg/day in

females LOAEL = 228.9 mg/kg/day in males and 281.5 based on increased incidences of retinal atrophy

No evidence of carcinogenicity.

870.4300 Chronic/ Carcinogenicity

- rat 40345607, 41144701 (1986)

Acceptable/guideline 0, 40, 140 or 500 ppm 0/0, 1.9/2.4, 6.8/8.2, or 24.4/28.7 mg/kg/day, M/F NOAEL = 24.4 mg/kg/day in males, 8.2 mg/kg/day in

females

LOAEL = not achieved in males and 28.7 based on inhibition of brain glutamate synthetase in fem ales at

130 weeks

No evidence of carcinogenicity.

870.4300 Carcinogenicity

mice 40345609, 41144702 (1986)

Acceptable/guideline 0, 20, 80, 160 (males only) or 320 (females only) ppm 0/0, 2.83/4.23, 10.82/16.19 or 22.60/66.96 mg/kg/day, M/F NOAEL = 10.82 mg/kg/day in males, 16.19 mg/kg/day

in females LOAEL = 22.60 mg/kg/day in males, 63.96 mg/kg/day in females based on increased mortality and glucose levels and consistent changes in glutathione levels in males, increased glucose levels and decreased albumi n and total proteins

No evidence of carcinogenicity.

870.5265

Reverse Mutation Assay Accession No. 072962 (1984)

Acceptable/guideline 0, 5, 10, 50, 100, 500, and 1000 μg/plate In a bacterial cell gene reverse mutation assay Salmonella typhimurium strains TA98, TA100, TA1535 and TA1537 were exposed to glufosinate ammonium (92.1% a.i.) at concentrations of 0, 5, 10, 50, 100, 500, and 1000 μg/plate in the presence and absence of mammalian metabolic activation (S9

- mix).

No increases in mutation frequ encies, with or without metabolic activation, were noted in any of the test strainsPage 38 of 45

Guideline No./ Study Type MRID No. (year)/

Classification /Doses Results

at any of the doses tested. Virtually total inhibition of growth was noted in all strains at the highest dose, 1000 μg/plate. Therefore, the requirement that chemicals be tested to the limits of cytotoxicity was satisfied. The positive controls, 2

- aminoanthracene, AF

- 2, 1

- ethyl

- 2

- nitro

- 3

- nitroso

- guanidine, 9

- amino

- acridine, and 2

- nitro

fluorine, induced the appropriate responses. Therefore the test systems were sensitive to agents that induce gene mutation. Under the conditions of the test, glufosinate

ammonium failed to cause reverse mutations in bacteria

with and without metabolic activation.

870.5300 Detection of gene mutations in

somatic cells in

culture 40445616 ( 1988)

Acceptable/guideline 50 to 5000 μg/mL 300 to 5000 μg/mL (S9

- activated doses). In a mouse lymphoma L5179Y forward mutation assay,

HOE 039866 was tested at seven nonactivated doses of 50 to 5000 μg/mL or at six S9

- activated doses of 300 to 5000 μg/mL.

HOE 39866 did not increase the mutation frequency at the thymidine kinase locus. The solvent controls gave acceptable values and the positive controls ethylmethanesulfonate (nonactivated) and 3

- methylcholanthrene (S9

- activated) provided evidence

that th e assay had adequate sensitivity for detecting mutagenicity.

870.5395

In vivo mammalian cytogenetic tests 41144704 (1986)

Acceptable/guideline 100, 200, and 350 mg/kg by

gavage In a mouse micronucleus assay 13 groups of mice (5/sex/dose) received a single administration of HOE 039866 at dose levels of 100, 200, and 350 mg/kg by gavage. A positive control group received 50 mg/kg of cyclophosphamide. After dosing, the animals wer e sacrificed at 24, 48, and 72 hrs., and the erythrocytes from the bone marrows were sampled at these times. The results indicated the test agent had no effect on

micronucleus formation.

870.5500

Bacterial DNA damage or repair test Accession No. 072962 (1984)

Acceptable/guideline 0, 50, 100, 500, 1000, 5000 or 10,000 μg/plate. In a DNA damage/repair assay, glufosinate ammonium was exposed overnight to B. subtilis that lacks the capacity for repair (H45) at concentrations of 0, 50, 100, 500, 1000, 5000 or 10,000 μg/plate. Glufosinate ammonium was also exposed, at the same dose levels, to an isogenic sister strain which has the capacity for DNA repair (H17).

Under the conditions of the study, no difference in the inhibition of growth between these two str ains was noted at any of the doses tested. Since the test measures the inhibition of growth in response to the test article, the requirement that chemicals be tested to the limits of cytotoxicity was satisfied. The positive controls, 2

- (2

- furyl)

- 3

- (5

- nit ro

- 2

- furyl)acrlamide (AF

- 2), caused a differential growth inhibition, whereas the negative controls (NaOH, HCL, and Kanamycin) produced no significant difference in growth inhibition. The test system was therefore sensitive to agents that damage

DNA. Und er the conditions of the test, the test article failed to cause damage to DNA that could be detected by this repair assay.

870.5550

Unschedule DNA synthesis in 40345614 (1984)

Acceptable/guideline 0.1 to 5240 μg/mL In an unscheduled DNA synthesis assay (MRID 40345614), primary rat hepatocyte cultures were exposed to HOE 039886 in deionized water at 15Page 39 of 45

Guideline No./ Study Type MRID No. (year)/

Classification /Doses Results

mammalian cells in

culture concentrations ranging from 0.1 to 5240 μg/mL for 18

- 19 hours. HOE 039866 was tested up to cytotoxic

concentrations as evidenced by decreased survival rate

as low as 34% There was no evidence that unscheduled DNA synthesis was induced by the test material.

870.6200 Acute Neurotoxicity

- rat 45190704 (1999)

Acceptable/nonguideline 0, 10, 100 or 500 mg/kg NOAEL= 500 mg /kg in males and females

LOAEL= Not established in both sexes

870.6200 Acute Neurotoxicity

- rat 45190703 (1999)

Acceptable/nonguideline 0, 10, 100 or 500 mg/kg NOAEL= 500 mg/kg in males and females

LOAEL= Not established in both sexes

870.6200b Repeat Dose Neurotoxicity

rat (37

- day study) 45179101, 45179102, 45297001

(2000) Acceptable/nonguideline 0, 20, 200 or 2000 ppm 0/0, 1.5/1.8, 14.9/17.1 or 143.3/161.5 mg/kg/day, M/F NOAEL= 1.5 mg/kg/day in males, 1.8 mg/kg/day in

females LOAEL= 14.9 mg/kg/day in males, 17.1 mg/kg/day in females, based on the inhibition of glutamate synthetase

in the brain

870.6200b Repeat Dose Neurotoxicity

rat (90

- day study) 42768201 (1993)

Unacceptable/guideline 0, 7500, 10000 or 20000 ppm 0/0, 521.45/573.79,

685.95/740.57 or 1351.09/1442.64 mg/kg/day,

M/F NOAEL= Not established LOAEL= 521.45 mg/kg/day in males, 573.79 mg/kg/day

in females based on increases in the incidence of decreased exploratory activity, decreased alertness, decreased startle response and meiosis

870.6300. Developmental Neurotoxicity study

– rats. 46455701 (2004)

Acceptable/Non

- guideline 0, 14, 69 or 292 mg/kg/day (during gestation) Maternal: NOAEL = 69 mg/kg/day. LOAEL = 292 mg/kg/day based on decreased body weight, body weight gain and food consumption during gestation and lactation. Developmental:

NOAEL

– Not established. LOAEL = 14 mg/kg/day based on altered brain morphogenics.

870.7485

Metabolism and pharmacokinetics

- rat 43766913 (1993)

Acceptable/nonguideline 2.0 mg/kg single dose In a metabolism study (85

- 1), groups of Wistar rats (5/sex) received a single dose (2 mg/kg) of 14C

- Hoe 039866 (glufosinate ammonium) by gavage. The majority of the radioactivity (95

- 98% of the dose) was eliminated during the first 24 hrs after dosing. The parent compound, Hoe 039866, accounted for most of the eliminated radioactivity in the urine and feces of both males (80% of the dose) and females (73% of the dose). The metabolite, Hoe 061517, was consistently

found in both urine and feces of both sexes. Hoe 099730
(7

- 8% of the dose) and Hoe 042231 ( 3% of the dose)

were found in the feces of both male and female rats and

none in the urine.

870.7485

Metabolism and pharmacokinetics

- rat 43766914, 43778402 (1995)

Acceptable/nonguideline 500 mg/kg single dose In a metabolism study, groups of Wistar rats (5/sex or 2/sex) received a single dose (500 mg/kg) of 14C

- Hoe 039866 (glufosinate ammonium) by gavage. Animals were sacrificed at various times (2, 6, 24, and 96 hrs) after dosing. The majority of the ra dioactivity was eliminated during the first 24 to 48 hrs after dosing. The parent compound, Hoe 039866, accounted for the majority of the radioactivity eliminated in the excreta of
both males ( 80% of the dose) and females (88% of the dose). This finding is consistent with the results of aPage 40 of 45

Guideline No./ Study Type MRID No. (year)/

Classification /Doses Results

previous metabolism studies (MRID No. 40345638 and MRID No. 43766913). The metabolite, Hoe 061517, was consistently found in both urine (0.22

- 1.20% of the dose) and feces (0.44

- 1.36% of the dose) of both sexes.

Hoe 0997 30 was found in feces (0.28

- 1.72% of the dose) of both male and female rats and barely above or at the level of the detection in the urine of both sexes (0.02

- 0.04% of the dose). Hoe 042231 was mainly found in
the feces of both male and females ( 0.2

- 0.28% of the dose). Very little if any of administered Hoe 039866 was sequestered in any tissues examined.

870.7485

Metabolism and pharmacokinetics

- rat 40345640 (1985)

Acceptable/nonguideline 30 mg/kg single dose Groups of Wistar rats (5/sex) were orally ad ministered a single nominal dose (30 mg/kg) of 14C

- HOE 039866. Rapid elimination during the first 24 hr for both males and females was observed. The major route of excretion was via feces (88% and 84% of the administered radioactivity for males and femal es, respectively). Within seven days of post dosing, greater than 94% of the dose was eliminated. Kinetics analysis indicated that the process of excretion was a two

- phase process. The tissue radioactivity level for kidneys, liver and gonads was just ab ove the background level.

870.7485

Metabolism and pharmacokinetics

- rat 43766913 (1993)

Acceptable/nonguideline 2.0 mg/kg single dose In a metabolism study (85

- 1), groups of Wistar rats (5/sex) received a single dose (2 mg/kg) of 14C

- Hoe

039866 (glufosinate ammonium) by gavage. The majority of the radioactivity (95

- 98% of the dose) was eliminated during the first 24 hrs after dosing. The parent compound, Hoe 039866, accounted for most of the eliminated radioactivity in the urine and feces of

both males (80% of the dose) and females (73% of the dose). The metabolite, Hoe 061517, was consistently

found in both urine and feces of both sexes. Hoe 099730
(7

- 8% of the dose) and Hoe 042231 ( 3% of the dose)

were found in the feces of both male and female rats and

none in the urine.

870.7485

Metabolism and pharmacokinetics

- rat 40345642 (1985)

Acceptable/nonguideline 2.0 mg/kg/day (repeat dose 14 days) Groups of Wistar rats (6/sex) were orally administered (gavage) unlabeled HOE 039866 for 14 days and 14 C

HOE039866 at the 15th day at a nominal dose of 2 mg/kg. The majority of the radioactivity was excreted within 24 hr after the last dose. The major route of

elimination was via feces. There was also a two

- phased elimination process. More radioactivity was found in the tissues of animals dosed repeatedly than that of animals receiving a single dose.

870.7600

Dermal Penetration

rat 40345620 (1986)

Acceptable/guideline 0, 0.1, 1.0 or 10.0 mg/6cm2 The results indicate that at the low dose (0.1 mg) 42.5 to 50.8% of the applied radioactivity was absorbed whereas at the high dose (10 mg) 26% was absorbed. After removal and washing of the treated skin a substantial amount of the radioactivity still remained in the skin, and it was gradually absorbed and eli minated. Radioactivity was found in both feces and urine samples, but the majority of HOE 039866 was eliminated in the urine. In all organs/tissues examined, radioactivity was

found to reach a maximum level either at four or 10 hr after exposure. Subseq uently, the radioactivity dropped rapidly. The amount of radioactivity found in the brain was very minimal relative to that of kidneys and liver.Page 41 of 45

Guideline No./ Study Type MRID No. (year)/

Classification /Doses Results

870.7600. Dermal penetration

– rat 45922103 (1995)

Acceptable/Guideline 12, 116 or 1218 μg/cm2 . A dermal absorption factor of 9% can be supported based on similar total absorbed and remaining on the

skin at 10 and 24 hours

HOE 061517 Metabolite

870.3100

90

- Day oral toxicity

rodents

- rat 44076206 (1988)

Acceptable/guideline) 0, 400, 1600 or 6400 ppm 0/0, 30/32, 102/113 or 420/439 mg/kg/day M/F NOAEL = 102 mg/kg/day in males, 113 mg/kg/day in

females LOAEL = 420 mg/kg/day in males, 439 mg/kg/day in females based on increased in reticulocytes and increased in absolute and relative liver weights in males

870.3100

90

- Day oral toxicity

rodents

- mice 44076207 (1989)

Acceptable/guideline) 0, 320, 1600, 3200 or 8000 ppm 0/0, 46/47, 209/220, 496/561 or 1121/1340 mg/kg/day M/F NOAEL = 1121 mg/kg/day in males, 1340 mg/kg/day in

females

LOAEL = Not established

870.3700a

Prenatal developmental in

rodents

- rat 44076209 (1994)

Acceptable/nonguideline 0, 100, 300 or 900 mg/kg/day Maternal : NOAEL = 300 mg/kg/day LOAEL = 900 mg/kg/day based on one death and clinical findings (persistent piloerection and/or increased urinary output) Developmental : NOAEL = 300 mg/kg/day LOAEL =900 mg/kg/day based on increases in the

incidences of total litter loss and in the fetal and litter incidences of wavy and/or thickened ribs

870.3700b Prenatal developmental in

nonrodents

- rabbit 44076210 (1994)

Unacceptable/guideline 0, 50, 100 or 200 mg/kg/day Maternal: NOAEL = 50 mg/kg/day LOAEL = 100 mg/kg/day based on increased abortions, mortality, and reductions in food and water consumption, body weight gain, and fecal output

Develo pmental: NOAEL = 200 mg/kg/day

LOAEL = Not observed

HOE 099730 metabolite

870.3100

90

- Day oral toxicity

rodents

- rat 44076201 (1994)

Acceptable/guideline 0, 400, 2000 or 10,000 ppm 0/0, 29/32, 147/162 or 738/800 mg/kg/day M/F NOAEL = 147 mg/kg/day in males, 162 mg/kg/day in

females LOAEL = 738 mg/kg/day in males, 800 mg/kg/day in females based on glutamine synthetase inhibition in the

brain

870.3100

90

- Day oral toxicity

rodents

- mice 44076202 (1994)

Acceptable/guideline 0, 500, 2000 or 8000 ppm 0/0, 83/110, 324/436 or 1296/1743 mg/kg/day M/F NOAEL = Not established for males, 110 mg/kg/day in

females LOAEL = 83 mg/kg/day in males, 436 mg/kg/day in females based on glutamine synthetase inhibition in the

brain

870.3150

Subchronic

Nonrodent Oral Toxicity

- dog 44076203 (1994)

Acceptable/guideline 0, 500, 2000 or 8000 ppm 0/, 19/21, 72/79 or 289/300 mg/kg/day M/F NOAEL = 19 mg/kg/day in males, 21 mg/kg/day in

females LOAEL = 72 mg/kg/day in males, 79 mg/kg/day in females based on glutamine synthetase inhibition in the

brain

870.3700a

Prenatal developmental in

rodents

- rat 44076204 (1993)

Acceptable/guideline 0 or 1000 mg/kg/day Maternal : NOAEL = 1000 mg/kg/day

LOAEL = Not observed Developmental : NOAEL = 1000 mg/kg/day

LOAEL = Not observed

870.3700b Prenatal developmental in

nonrodents

- rabbit 44076205 (1995)

Acceptable/guideline 0, 64, 160 or 400 mg/kg/day Maternal : NOAEL = 64 mg/kg/day LOAEL = 160 mg/kg/day based on reduced feed consumption Developmental : NOAEL = 64 mg/kg/day

LOAEL = 160 based on uni

- or bilateral extra at the 13 thPage 42 of 45

Guideline No./ Study Type MRID No. (year)/

Classification /Doses Results

thoracic vertebra

870.6200 Acute Neurotoxicity

- rat 45190702 (1999)

Acceptable/nonguideline 0, 100, 1000 or 2000 mg/kg NOAEL= 1000 mg/kg in males and females LOAEL= 2000 mg/kg in males and females based on clinical signs of toxicity including sedation, ruffled fur,

and diarrhea

870.6200 Acute Neurotoxicity

- rat 45190701 (1999)

Acceptable/nonguideline 0, 100, 1000 or 2000 mg/kg NOAEL= 100 mg/kg in males and females LOAEL= 1000 mg/kg in males and females based on decreased body weight gain

870.6200b Repeat Dose Neurotoxicity

rat 45179101, 45179102, 45297001

(2000); Acceptable/nonguideline 0, 20, 200 or 2000 ppm 0/0, 1.6/1.75, 15.5/17.7 or 158.9/179.4 mg/kg/day, M/F NOAEL= 158.9 mg/kg/day in males, 179.4 mg/kg/day

in females

LOAEL= Not established in males and females

HOE 058192 (L

- i somer of glufosinate ammonium)

870.3100

90

- Day oral toxicity

rodents

- rat 44068501 (1989)

Acceptable/guideline 0, 25, 250, 1250 or 2500 ppm 0/0, 1.9/1.9, 18.5/19.8,

91.8/100.3 or 186.4/194.3 mg/kg/day M/F NOAEL = 18.5 mg/kg/day in males, 19.8 mg/kg/day in

females LOAEL = 91.8 mg/kg/day in males, 100.3 mg/kg/day in

females based on increased ammonia levels in the plasma and urine and slight kidney weight increases

870.3150

Subchronic

Nonrodent Oral Toxicity

- dog 44068502 (1989)

Acceptable/guideline 0, 2, 5 or 8.5 mg/kg/day NOAEL = 2 mg/kg/day LOAEL = 5 mg/kg/day based on increased plasma and kidney ammonia levels

870.3700b Prenatal developmental in

nonrodents

- rabbit 43829405 (1992)

Acceptable/guideline 0, 1.25, 2.50, or 5.00 mg/kg/day Maternal : NOAEL = 1.25 mg/kg/day ; LOAEL = 2.50 mg/kg/day based on decrease in body weight gains and food consumption, neurotoxic signs and abortions Developmental : NOAEL = 1.25 mg/kg/day; LOAEL = 2.50 mg/kg/day based on an increase in post implantation loss (fetal resorptions)Page 43 of 45

Appendix B. Magnitude of the Residue Considerations

Citrus Fruit For citrus fruits, a total of twenty three magnitude of the residue field trials were conducted for orange, lemon, and grapefruit . A summary of the residue data is presented in Table B.1. Eight of

the 23 trials used a non

- ionic antifoam adjuvant. Following t hree broadcast a pplications at a target rate of 1.50 lb ai/A/application, with a 14

- day RTI and a 14

- day PHI, r esidues of glufosinate ammonium (GA) and its two metabolites, glufosinate propanoic acid (MPP) and N

acetylglufosinate (NAG) were not detected above the limit of quantitation ( LOQ ) (0.05 ppm) in/on oranges, lemon s, or grapefruit

. R esidue decline studies performed on each of the three representative crop types at PHIs of 7, 11, 14, 17, and 21 days showed residues below the LOQ

for all residues of concern. Accordingly, the appropriate tolerance level for citrus fruit is 0.15 ppm [computed as the sum of the LOQs for each of the three residues of concern].

Stone Fruit For peach, nine crop field trials were conducted, all without adjuvant. Following two broadcast applications at a target rate of 1.50 lb ai/A/application, with a 28

- day RTI and a 14

- day PHI, t here

were no residues of GA

, MPP or N AG detected above the LOQ (0.05 ppm) in/on peach samples

. There were no residue decline studi es performed for p each.

For plum and cherry, six crop field trials each were conducted. Five of the 12 trials for plum and

cherries used a non

- ionic antifoam adjuvant. Following t wo broadcast applications at a target rate
of 1.50 lb ai/A/application, with a 28

- day RTI an d a 14

- day PHI, r esidues of GA and NAG were not detected above the LOQ (0.05 ppm ). One cherry trial and one plum trial showed MPP residues above the LOQ. Thus, f or cherries, t he highest average field trial (HAFT) was 0.083 ppm with a maximum residue of 0.098 ppm MPP

. For total glufosinate ammonium, the cherry

HAFT was 0.183 ppm with a maximum residue of 0.198 ppm. For plums, the HAFT was 0.0655 ppm with a maxi mum residue of 0.066 ppm MPP. For total glufosinate ammonium, the plum

HAFT was 0.1655 ppm wi th a maximum residue of 0.166 ppm. Results from the residue decline studies performed on both crops at PHIs of 7, 11, 14, 17, and 21 days indicated that total glufosinate ammonium residues in cherry and plum were found to be near or below the LOQ at all

P HIs; therefore, a trend was not observed. The recommended stone fruit tolerance level was based on the cherry data; the maximum total glufosinate ammonium residue of 0.198 ppm indicates a stone fruit tolerance level of 0.25 ppm is appropriate.

Pome Frui t For pear, six crop field trials were conducted. In all trials, ammonium sulfate fertilizer was added

to each tank mixture. Two sites received a non

- ionic antifoam adjuvant. Following t hree broadcast applications at a target rate of 1.50 lb ai/A/applic ation, with a 14

- day RTI and a 14

- day
PHI, r esidues of GA and NAG in/on pear were less than the LOQ (0.05 ppm). However, one pear trial found MPP residues above the LOQ . Specifically, the pear HAFT for MPP was 0.081 ppm,

and the maximum residue was 0.089 ppm. For total glufosinate ammonium, the pear HAFT was

0.181 ppm with a maximum residue of 0.189 ppm. Results from the residue decline study with PHIs of 7, 9, 14, 16, and 21 days showed all residues of concern were below the LOQ at all sampling intervals

.

The established apple tolerance of 0.05 ppm is based on the same use pattern used in the pear trials. Accordingly, it is appropriate to recommend a pome fruit tolerance based on the pear trials. The maximum total glufosinate ammonium residue s of 0.189 ppm indicates a pome fruit tolerance level of 0.25 ppm is appropriate.Page 44 of 45

Olive For olive, three crop field trials were conducted. In all trials, ammonium sulfate fertilizer was added to each tank mixture. In two of the trials, a non

- ionic ant ifoam adjuvant was also added to

the tank mixture. Following three broadcast applications at a target rate of 1.50 lb ai/A/application, with a 14

- day RTI and a 14

- day PHI, t here were no residues of GA, MPP, or

NAG detected above the LOQ (0.05 ppm) in/on o live samples

. There were no residue decline

studi es performed for olive. The appropriate tolerance level for olive is 0.15 ppm [computed as the sum of the LOQs for each of the three residues of concern].

Sweet Corn For sweet corn, twelve crop field tria ls were conducted (see Table B.2). Two of the trials in Arlington, Wisconsin were conducted in the same field in the same year, and therefore cannot be considered independent. In all trials, ammonium sulfate fertilizer was added to each tank mixture,

but no adjuvant was used. Following two foliar applications at a rate of 0.375 lb ai/A, with a RTI of 14 days and a PHI of 30

- 50 days, maximum total glufosinate ammonium residues in/on sweet corn ears, forage and stover were 0.19, 0.79, and 3.70 ppm, respect ively. The tolerance levels for sweet corn commodities were determined using the Organization for Economic Cooperation and Development (OECD) tolerance calculation procedures. Thus, the recommended tolerance levels for sweet corn ears, forage, and stover are 0.30, 1.5, and 6.0 ppm, respectively.

TABLE B.1. Summary of Total Glufosinate Ammonium Residue s (sum of GA + MPP + NAG) in Fruits

and Olive.

Commodity Total Applic. Rate

(lb ai/A) PHI

(days) Residue Levels (ppm)

n 1 Min. Max. HAFT Median Mean

Orange 4.38 to 4.61 14 24 <0. 1 5 <0. 1 5 <0. 1 5 NA NA

Lemon 4.50 to 4.53 14 10 <0. 1 5 <0. 1 5 <0. 1 5 NA NA

Grapefruit 4.47 to 4.58 14 12 <0. 1 5 <0. 1 5 <0. 1 5 NA NA

Pear 4.45 to 4.57 14 12 <0.15 0.189 0.181 0.15 0.155

Cherry 3.00 to 3.11 14 12 <0. 1 5 0.198 0.183 0.15 0.156

Plum 2.92 to 3.03 14 12 <0. 1 5 0.166 0.1655 0.15 0.153

Peach 2.86 to 3.07 14 18 <0.15 <0.15 <0.15 NA NA

Olive 4.50 to 4.52 14 6 <0.15 <0.15 <0.15 NA NA

1 Two values per field trial.Page 45 of 45

TABLE B.2. Summary of Total Glufosinate Ammonium Residue s (sum of GA + MPP + NAG) in Sweet Corn.

Commodity Total Applic. Rate

(lb ai/A) PHI

(days) Residue Levels (ppm)

n 1 Min. Max. HAFT Median Mean

Sweet Corn,

Ears 0.75 30

- 50 11 0.10 0.19 0.19 0.10 0.11

Sweet Corn, Forage 0.75 30

- 50 11 0.18 0.79 0.79 0.31 0.39

Sweet Corn,

Stover 0.75 30

- 50 11 0.16 3.7 3.7 1.53 1.42

1 One value per field trial: replicate averages.