SCIENCE FINDINGS

SUMMARY SCIENCE STATEMENTS

Acute toxicity data indicate that has low toxicity via oral, dermal and inhalation routes of exposure. The technica l product is classified in toxicity category I [DANGER] based on an acute eye irritation study conducted with the free acid. The formulated end-use product ( has low toxicity and is classified in toxicity category IV [Caution].

In an acute neurotoxicity study in ra ts with there were no treatment-related effects on Functional Observ ation Battery (FOB), motor activity, or neuropathological observations. The systemic No Observed Adverse Effect Level (NOAEL) was 1000 mg/kg based on transient clinical observations of fecal soiling in males and urine soiling in females observed at 2000 mg/kg bw, the highest dose tested [HDT]. In a chronic neurotoxicity study in rats the NOAEL was equal to or greater than 1,000 mg/kg/day [HDT].

was negative in all mutagenici ty studies, except for an in vitro chromosome aberration assay utilizing rat lym phocytes. In this assay, induced chromosome aberrations without S9 activation, but only at cytotoxic concentrations. The clastogenic response was induced secondary to toxicity.

In a rat developmental study the NOAEL fo r maternal and developmental toxicity was equal to or greater than 1,000 mg/kg/day [HDT ]. In a developmental toxicity study in rabbits with the NOAEL for maternal toxicity was 250 mg/kg/day and the

-2-developmental NOAEL was equal or greater than 500 mg/kg/day. Maternal toxicity was observed at 500 and 750 mg/kg/day [HDT] in the form of decreased body weights and clinical observations of uncoordinated gai t. Ulcers and erosions of the glandular mucosa of the stomach were observ ed in the 500 and 750 mg/kg/day dose groups. Similar toxic effects were also observed in a developmental study in rabbits with the formulated triisopropanolam ine (TIPA) salt of Developmental toxicity could not be determined in rabbit study since the 750 mg/kg/day group was removed from the st udy due to the severity of the clinical signs (body weight changes, decreased f ood consumption and a decreased amount of feces). However, in the rabbit devel opmental study with developmental toxicity was demonstrated by a decrease in fetal body weights at 520 mg acid equivalents (ae)/kg/day. In a 2-generation reproduction study in rats, there was no evidence of parental, reproductive, or offspr ing toxicity observed after exposure to up to 1000 mg/kg/day [HDT]. The developmental toxicity studies and the 2-generation reproduction study did not exhibi t quantitative or qualit ative susceptibility.

There were no systemic toxic effects obs erved at 1000 mg/kg/day [HDT] in a 28-day dermal toxicity study in rats with However, dermal toxicity was indicated by slight epidermal hyperplasia in males at the HDT.

The database on indicates that the stomach, ileum and cecum are targets for this compound. In a 90-day toxicity study in dogs the NOAEL was 282 mg/kg/day for males and 232 mg/kg/day for females based on slight diffuse hyperplasia and hypertrophy of the mucosal epithelium of t he stomach at 1070 mg/kg/day in males and 929 mg/kg/day in females. In the 1-year ch ronic toxicity study in dogs, the NOAEL was 99 mg/kg/day for males and 93 mg/kg/day for females based on thickening of the stomach, slight lymphoid hyperplasia of t he gastric mucosa, and slight chronic mucosal inflammation at the HDT. In a 90-day mouse dietary study, no toxicity was observed at 1000 mg/kg/day [HDT]. In a 90-day rat feeding study the NOAEL was 1000 mg/kg/day [HDT] for females and 500 mg/kg/day for males based on hyperplasia of the mucosal epithelium of the ileum and the cecum at 1000 mg/kg/day [HDT].

In the mouse chronic feeding study the NOAEL was 1000 mg/kg/day [HDT] for males and 250 mg/kg/day for females. In the rat chronic feeding study the NOAEL was 50 mg/kg/day based on cecal enlargement, slight mucosal hyperplasia (males) and slightly decreased body weights at 500 mg/kg/day.

has been classified as "not likely" to be carcinogenic to humans. No increases in any tumors were found in carcinogenicity studies in rats and mice.

In a metabolism study in rats, was rapidly absorbed, distributed, and excreted following oral administration. Tissue distribution and bioaccumulation were minimal; <0.73% of administered dose [AD] wa s recovered in tissues after 7 days for all dosing groups. The highest levels of radioactivity were found in the skin and carcass. was excreted unchanged, indicati ng an absence of metabolism. The AD

-3-was recovered as parent compound in 100% of the feces and = 96% of the urine. Three unknown components found in urine (= 4 %) were also detected in similar quantities in dose formulations, suggesting that they were trace impurities.

Based on aminopyralid's low toxicity, an acute Reference Dose (RfD) for the general population is not required.

The chronic RfD for is 0.5 mg/kg/day. This value is based on the NOAEL of 50 mg/kg/day in the rat combined chr onic toxicity/carcinogenicity study with a 100-fold uncertainty factor to account for interspecies extrapolation (10X) and intraspecies variability (10X). An additional sa fety factor to protect infants and children is not required, due to the toxicity properties of the material and the conservative nature of the exposure estimates.

A DEEM chronic exposure analysis was conduct ed using the tolerance levels for wheat grain and meat commodities and assuming 100% of crops treated with The estimated exposures to US-populati on and relevant sensitive sub-population groups were all at least 3 orders of magnitude below the RfD (< 1% RfD).

Based on the PRZM/EXAMS model, the estimated environmental concentrations (EECs) of for chronic exposures are estimated to be 1.937 parts per billion (ppb) for surface water and 0.630 ppb for ground water. The chronic estimated water concentrations derived from surface water

m odeling results were significantly higher than the modeled ground water concentrations, and therefore protective of potential exposures vi a ground water sources of drinking water when

LifeLineTM Version 2.0 to determine aggregate pesticide exposures from pesticide residues in incorporated into aggregate exposure estimates. The EEC’s were incorporated into

There are no requested uses for that are considered residential and neither handler nor post-application residential exposures from uses around homes are expected to occur. However, the use on campgrounds and other recreation areas to control vegetation has the potential to result in short-term post-application incidental oral exposures for infants and children via hand-to mouth transfer of residues and ingestion of contaminated grass and soil. For children with a 15-kg body weight exposed via the hand-to-m outh route, the potential MOE was 150,000. Post-application exposure via inhalation is not expected to occur.

The source of human exposure results from diet ary exposure from food and drinking water, and short term incidential oral exposure, a short term oral exposure of children to treated campgrounds.. Aggregating these exposure estimates gives a com b ined potential level of 0.0033
mg /kg/day, for the highest exposed group, children 1-2 years of age. The m a rgin of exposure (MOE) associated with this Tier I exposure estimate is 32,000, greatly above the acceptable limit (MOE = 100). EPA thus concludes that there is reasonable certainty that no harm will com e from aggregate exposure to residues.

-4-Based on labeled uses, the occupational exposure is expected to be short- to interm ediate-term and no long-term exposure is expected. Based on the available toxicological information, dermal exposures do not result in any adverse systemic effect; therefore, dermal exposures were not included into the estimation of occupational risk to workers. Short- and intermediate-term oral and inhalation exposures are being regulated based on the effects seen in the developmental rabbit toxicity study, which showed a NOAEL of 104 m g /kg/day.

The highest potential exposure was estimated to Mixer-Loaders working on aerial applications of 0.11 lb ae/A, for up to 1200 acres applied per day. The corresponding MOE is 40,000.

Dietary tolerances are established for free and conjugated residues in the following crop food/feed com m odities:

Com m odity Parts per million

Grass, forage 25

Grass, hay 50

Wh eat, bran 0.1

Wh eat, forage 2.0

Wh eat, grain 0.04

Wh eat, hay 4.0

Wh eat, straw 0.25
Aspirated grain fractions 0.2

Tolerances also listed for the parent in or on the following animal com m odities:

Commodity Parts per Million
Cattle, fat 0.02

Cattle, meat 0.02
Cattle, meat byproducts, excluding kidney 0.02

Cattle, kidney 0.3

Goat, fat 0.02

-5-Goat, meat 0.02
Goat, meat byproducts, excluding kidney 0.02

Goat, kidney 0.3

Horse, fat 0.02

Horse, meat 0.02
Horse, meat byproducts, excluding kidney 0.02

Horse, kidney 0.3

Milk 0.03
Sheep, fat 0.02
Sheep, meat 0.02
Sheep, meat byproducts, excluding kidney 0.02

Sheep, kidney 0.3

In aquatic systems, the primary route of degradation is photolysis, where a laboratory experiment yielded a half-life of 0.6 days. In addition to CO2, oxamic and were identified as major degradates. was stable to direct hydrolysis and in anaerobic sediment-water systems. In aerobic sediment-water systems, degradation proceeded slowly, with observed tota l system half-lives of 462 to 990 days. The degradation resulted in the formation of non-extractable residues and no other major products.

Under aerobic conditions, degradation of in five different soils resulted in the production of CO2 and non-extractable re sidues. Half-lives ranged from 31.5 to 533.2 days in 5 soils. For risk assessment purposes, EPA used a half-life of 103.5 days.

photolyzed moderately slowly on a soil surface. The half-life was 72 days and CO2, non-extractable residues and small amounts of acidic volatiles were the degradates.

is weakly sorbed to soil. A laboratory Freundlic h adsorption isotherm study with 8 US and European soils yielded 48-hour Kd values of 0.03 to 0.72 mL/g; adsorption Koc values were 1.05 to 24.3 mL/g.

-6-Two field dissipation studies were performed (in California and Mississippi). The results indicate that is likely to be non- persistent and relatively immobile in the field. Half-lives of 32 and 20 days were determined, with minimal leaching below the 15 to 30 cm soil depth.

has been shown to be practically non-toxic to birds, fish, honeybees, earthworms, and aquatic invertebrates. is slightly toxic to eastern oyster, algae and aquatic vascular plants. The log Kow is less than 3 and thus is not expected to bioaccumulate in fish tissue.

There are no acute or chronic risks to non-target endangered or non-endangered fish, birds, wild mammals, terrestrial and aquatic invertebrates, algae or aquatic plants.

TECHNICAL CHEMICAL CHARACTERISTICS

Empirical Formula:

Molecular Weight:

Color; Off-white

Physical State: Powder

Odor: O dorless

Melting Point: 161.75 - 165.23o C

Density: 1.72 (20o C, relative to water at 4o C)

Solubility: Water 212 g/L (pH 5) 205 g/L (pH 7) 203 g/L (pH 9) 2.48 g/L (unbuffered) Acetone 29.2 g/L Ethyl Acetate 4 g/L Methanol 52.2 g/L 1,2-dichloroethane 0.189 g/L Xylene 0.043 g/L Heptane less than 0.010 g/L

Vapor Pressure: 7 .14 x 10 -11 mm Hg at 20o C

-7-1.92 x 10 -10 mm Hg at 25o C

Dissociation Constant: pK
a = 2.56 at 20o C

Octanol/Water Partition Coefficient: l ogP = 0.201 (Unbuffered at 20o C) LogP = -1.75 (pH 5 at 20o C) LogP = -2.87 (pH 7 at 20o C) LogP = -2.96 (pH 9 at 20o C)

pH: 2 .31 (1% w/w solution/suspension)

Oxidizing or Reducing Action: none

Mobility: K d = 0.03 - 0.72

TOXICOLOGY CHARACTERISTICS

(formulated end-use product)

Acute Oral Toxicity (rats): Toxicity LD 50 Males and Females > 5000 mg/kg Category: IV

Acute Dermal Toxicity (rats): Toxicity LD 50 Males and Females > 5000 mg/kg Category: IV

Acute Inhalation Toxicity (rats): Toxicity LC 50 Males and Females > 5.79 mg/L Category: IV

Primary Eye

-8-Irritation (rabbits): Tox i city No irritation Category: IV

Primary Skin Irritation (rabbits): Toxicity Slight erythema at 24 and 72 hours, resolving by day 7 Category: IV

Dermal Sensitization (guinea pigs): Not a sensitizer

90-day dietary (rats): NOAEL = 1000 mg (TIPA) salt of kg/day (520 mg acid equivalents (ae)/kg/day) LOAEL = not determined

Developmental Toxicity (rabbit): M aternal NOAEL = 200 mg TIPA salt of /kg/day (104 mg ae/kg/day) Maternal LOAEL = 500 mg TIPA salt of /kg/day (260 mg ae/kg/day) based on severe inanition and body weight loss, decreased fecal output, and mild clinical observations of uncoordinated gait

Developmental NOAEL = 500 mg TIPA salt of /kg/day (260 mg ae/kg/day) Developmental LOAEL = 1000 mg TIPA salt of kg/day (520 mg ae/kg/day) based on decreased fetal body weights

Developmental Toxicity (rat): M aternal NOAEL = 1000 mg TIPA salt of kg/day (520 mg ae/kg/day) Maternal LOAEL = not determined

Developmental NOAEL = 1000 mg TI PA salt of kg/day (520 mg ae/kg/day) Developmental LOAEL = not determined

Mutagenicity: T he mutagenicity studies submitted for satisfy the

-9-mutagenicity test battery. was negative in all mutagenicity studies.

Metabolism (Non-guideline): 14 C- and 14 C-aminopryalid TIPA salt, when administered orally to rats, were bioequivalent in terms of absorption, distribution, met abolism, and excretion of the amino-dichloro-picolinate portion of the molecule(s).

Technical (manufacturing use product)

Acute Oral Toxicity (rats): Toxicity LD 50 Males and Females > 5000 mg/kg Category: IV

Acute Dermal Toxicity (rabbits): Toxicity LD 50 Males and Females >5000 mg/kg Category: IV

Acute Inhalation Toxicity (rats): Toxicity LC 50 Males and Females >5.5 mg/L Category: IV

Primary Eye Irritation (rabbits): Toxicity Corneal opacity in 1/3 through day 35 Category: I

Primary Skin Irritation (rabbits): Tox i city No irritation Category: IV

Dermal Sensitization

-10-(guinea pigs): Not a sensitizer

Acute Neurotoxicity Screening Battery (rat): N OAEL = 1000 mg/kg LOAEL = 2000 mg/kg based on fecal soiling in males and urine soiling in females

90-day dietary (rats): NOAEL Male = 500 mg/kg/day, Female = 1000 mg/kg/day LOAEL Male = 1000 mg/kg/day based on hyperplasia of the mucosal epithelium of ileum and cecum, Female = not determined

90-day dietary (dogs): NOAEL Male = 282 mg/kg/day, Female = 232 mg/kg/day LOAEL Male = 1070 mg/kg/day, Female = 929 mg/kg/day based on stomach histopathology (slight diffuse hyperplasia and hypertrophy of the mucosal epithelium)

28-day dermal (rats): Systemic NOAEL = 1000 mg/kg/day LOAEL = not determined

Dermal NOAEL Male = 100 mg/kg/day, Female = 1000 mg/kg/day LOAEL Male = 500 mg/kg/day based on histopathological changes (slight epidermal hyperplasia), Female = no

Developmental Toxicity (rabbit): M aternal NOAEL = 250 mg/kg/day Maternal LOAEL = 500 mg/kg/day based on decrease in body weight (GD 7-10), decreased food consumption, clinical observations of uncoordinated gait and ulcers and erosions of the stomach

Developmental NOAEL = 500 mg/kg/day Developmental LOAEL = not determined

Developmental Toxicity (rat): Maternal NOAEL = 1000 mg/kg/day Maternal LOAEL = not determined

Developmental NOAEL = 1000 mg/kg/day

-11-Developmental LOAEL = not determined

Two-Generation Reproduction (rat): P aternal NOAEL = 1000 mg/kg/day Paternal LOAEL = not determined

Reproductive NOAEL = 1000 mg/kg/day Reproductive LOAEL = not determined

Offspring NOAEL = 1000 mg/kg/day Offspring LOAEL = not determined

1 Year Chronic Feeding (dog): N OAEL Male = 99 mg/kg/day, Female = 93 mg/kg/day LOAEL Male = 967 mg/kg/day, Female = 1038 mg/kg/day based on thickening of stomach mucosa (females), and stomach histopathology in all animals (slight diffuse hyperplasia and hypertrophy of the mucosal epithelium, slight lymphoid hyperplasia of the gastric mucosa and very slight/slight chronic mucosal inflammation)

Chronic Neurotoxicity (rat): N OAEL = 1000 mg/kg/day LOAEL = not determined

Chronic Feeding/ Carcinogenicity (rat): N OAEL = 50 mg/kg/day LOAEL = 500 mg/kg/day based on cecal enlargement, slight mucosal hyperplasia (males) and slightly decreased body weights

Carcinogenicity (mouse): NOAEL Male = 1000 mg/kg/day, Female 250 mg/kg/day LOAEL Male = not determined, Female = 1000 mg/kg/day based on increased mortality

Mutagenicity: T he mutagenicity studies s ubmitted for satisfy the mutagenicity test battery. was negative in all mutagenicity studies, except for an in vitro chromosome aberration assay utilizing rat lymphocytes. In this assay, induced chromosome aberrations, but only at cytotoxic concentrations. The clastogenic response was induced secondary to toxicity.

-12-Metabolism: Low dose = 50 mg/kg High dose = 1000 mg/kg Repeated dose = 50 mg/kg/day (unlabeled) for 14 days, 50 mg/kg/day (labeled) on day 15 Recovery after 168 hrs: 96% in low dose (urine - 50%, feces - 43%, tissues - 0.1%, cage wash - 10%), and 95% in the repeated low dose (urine 59%, feces - 33%, tissues - 0.1%, cage wash - 3%). represented = 96% of administered dose (AD) in urine and 100% AD in feces. Three unknown components (= 4 %) found in urine were also found in dose formulations.

ECOLOGICAL CHARACTERISTICS

Avian Acute Toxicity: Bobwhite Quail: LD 50 >2250 mg a.e./kg bw

Avian Dietary Tox i city: Bobwhite Quail: 5-day LC 50 >5556 mg a.e./kg diet Mallard Duck: 5- day LC 50 >5496 mg a.e./kg diet

Avian Reproduction: Bobwhite Quail: No Observed Effect Concentration (NOEC) = not determined Lowest Observed Effect Concentration (LOEC) = 640 mg a.e./kg diet

Mallard Duck: No Observed Effect Concentration (NOEC) = 2623 mg a.e./kg diet Lowest Observed Effect Concentration (LOEC) > 2623 mg a.e./kg diet

Acute Mammalian Toxicity: Rattus rattus: LD 50 >5000 mg a.e./kg bw

Chronic Mammalian Tox i city: Rattus norvegicus: NOEL >1000 mg a.e./kg bw/day

Freshwater fish and amphibian Acute Toxicity: Bluegill Sunfish: 96-hour LC 50 >100 mg a.e./L Rainbow Trout: 96-hour LC 50 >100 mg a.e./L Northern leopard frog: 96-hour LC 50 >95.2 mg a.e./L

Estuarine/marine fish

-13-Acute Toxicity: Sheepshead minnow: 96-hour LC 50 >120 mg a.e./L

Freshwater Fish Early life-stage Toxicity: Fathead Minnow: N OEC = 1.36 mg a.e./L LOEC = 2.44 mg a.e./L MATC** = 1.82 mg a.e./L ** Defined as the geometric mean of the NOEC and LOEC

Freshwater Invertebrate Toxicity: Daphnia magna: 48-hour EC 50 >98.6 mg a.e./L

Freshwater Invertebrate Life-Cycle Toxicity: Daphnia magna: NOEC = 102 mg a.e./L (highest concentration tested) LOEC > 102 mg a.e./L

Estuarine/Marine Invertebrate Acute Toxicity: Eastern Oyster: 48-hour EC 50 >89 mg a.e./L Mysid: 96-hour LC 50 >100 mg a.e./L

Non-Target Insects Toxicity: Honey Bee Acute Contact: LD 50 >100 

### : g a.e./bee Acute Oral: LD 50 >117 

### : g a.e./bee

Seedling Emergency and Vegetative Vigor For

Seedling Emergence: Species EC25 (g a.i./ha) Most Sensitive Parameter Monocot - Barnyardgrass > 230.8 N one Monocot - Corn >230.8 N one Monocot - Onion 29.0 Fresh weight (Most Sensitive Monocot) Monocot - Wheat >230.8 N one Dicot - Cucumber >57.7 N one Dicot - Soybean 2.7 F resh weight (Most Sensitive Dicot) Dicot - Sugar Beet 14.0 F resh weight Dicot - Lettuce 20.0 F resh weight

-14-Dicot - Oilseed Rape 49.0 F resh weight >230.8 N one Dicot - Radish

Vegetative Vigor: Species E C25 (g a.i./ha) Most Sensitive Parameter Monocot - Barnyardgrass > 230.8 N one Monocot - Corn >230.8 N one Monocot - Onion 53.0 Fresh weight Monocot - Wheat >230.8 N one Dicot - Cucumber 12.0 S hoot length Dicot - Soybean 0.75 Shoot length Dicot - Sugar Beet 8.4 F resh weight Dicot - Lettuce 3.3 F resh weight Dicot - Oilseed Rape >230.8 N one Dicot - Radish 54.0 F resh weight

Non-target Aquatic Plant Toxicity (Tier II):

Vascular Plants Duckweed Lemna gibba: EC 50 > 88 mg a.e./L NOEC = 44 mg a.e./L

Nonvascular Plants Green algae Pseudokirchneriella subcapitata: ErC 50 = 30 mg a.e./L NOEC = 23 mg a.e./L

Marine diatom: Skeletonema costatum: E bC 50 = 70 mg a.e./L NOEC = 13 mg a.e./L

Freshwater diatom: Navicula pelliculosa: EC 50 = 18 mg a.e./L NOEC = 6 mg a.e./L

Blue-green algae: Anabaena Flos-aquae: not determined

has been shown to be practically non-toxic to birds, fish, honeybees, earthworms, and aquatic invertebrates. is slightly toxic to eastern oyster, algae and aquatic vascular plants. The log Kow is less than 3, indicating that is not expected to bioaccumulate in fish tissue. Tier II seedling emergence and vegetative vigor studies were conducted using the formulated product, Seedling emergence testing indicated that oni on was the most sensitive monocot (fresh shoot weight EC25 = 29 g a.i./ha), while soy beans were the most sensitive dicot (fresh shoot weight EC25 = 2.7 g a.i./ha). Vegetat ive vigor testing indicated that onion was

-15-again the most sensitive monocot (fresh shoot weight EC25 = 53 g a.i./ha). Similarly, soybeans were the most sensitive dicot (shoot length EC25 = 0.75 g a.i./ha). Grass species (barnyardgrass, corn and wheat) were among the least sensitive species tested in both the seedling emergence and vegetat ive vigor tests and had EC25 values that exceeded the maximum application rate tested. There are no acute or chronic risks to non-target endangered or non-endangered fish, birds, wild mammals, terrestrial and aquatic invertebrates, algae or aquatic plants.

ENVIRONMENTAL CHARACTERISTICS

In aquatic systems, the primary route of degradation is photolysis, where a laboratory experiment yielded a half-life of 0.6 days (corre cted for natural sunlight conditions). In addition to CO2, oxamic and were identified as major degradates, along with a number of minor 2-3 carbon chain lengt h acid amides. was stable to direct hydrolysis and in anaerobic s ediment-water systems. In aerobic sediment-water systems, degradation pr oceeded slowly, with observed total system half-lives of 462 to 990 days. The degradation resulted in the formation of non-extractable residues and no other major products.

Under aerobic conditions, degradation of in five different soils resulted in the production of no significant degradati on products beyond CO2 and non-extractable residues. Half-lives ranged from 31.5 to 533. 2 days, although material balance criteria were not met for 4 of the 5 soils; the soil meeting these criteria yielded a half-life of 103.5 days. By the end of the study, CO2 accounted for 66 to 73% of the applied (except in a Barnes Clay Loam soil at 27-30% of applied). Non-extractable residues were detected at 0 to 16% of applied radioacti vity at the end of the study, except for the test with a Houston Black Clay soil, where the non-extractable residues were 23-24% of applied.

photolyzed moderately slowly on a soil surface. The half-life was 72 days (corrected for natural sunlight and soil me tabolism) and CO2, non-extractable residues and small amounts of acidic volatiles were the degrates..

is weakly sorbed to soil. A laboratory Freundlic h adsorption isotherm study with 8 US and European soils yielded 48-hour Kd values of 0.03 to 0.72 mL/g; adsorption Koc values were 1.05 to 24.3 mL/g.

Two field dissipation studies were performed (in California and Mississippi). The results indicate that is likely to be non- persistent and relatively immobile in the field. Half-lives of 32 and 20 days were determined, with minimal leaching below the 15 to 30 cm horizon depth.

The nature of the residue in plants and animals is well understood. Based on the nature of residue studies (NOR) on grass and wheat, t he tolerance expression in or on grass forage, grass hay, wheat raw agricultural co mmodities and wheat processed products is

-16-the total parent both free and conjugated. Based on the NOR study on lactating goat, the tolerance expression in milk, meat and meat-byproducts is the unchanged parent, Tolerances are established for residues of as described in the Summary Science Statements of this Fact Sheet.

AGGREGATE EXPOSURES

As indicated by the Food Quality Protec tion Act (FQPA), 1996, the potential for concurrent exposure to via oral, dermal and inhalation routes must be assessed by EPA. This aggregate exposure c onsiders every possible non-occupational exposure route, including residues in food, in drinking water and residential exposure from indoor/outdoor non-crop uses. However, based on the available toxicologi cal information, dermal exposures do not result in any adverse systemic effect; ther efore, dermal exposures are not included into the estimation of aggregate risk for any duration of exposure. Short- and intermediate-term oral and inhalation exposures are being regulated based on the effects seen in the developmental rabbit toxi city study. However, the non-crop uses do not include any indoor uses; therefore, both handler and post-application inhalation exposures are expected to be negligible.

1. From Food and Feed Uses

Based on aminopyralid's low toxicity profile, an acute Reference Dose (RfD) for the general population or any of the popul ation sub-groups is not required.

The chronic Reference Dose (RfD) for is 0.5 mg/kg/day. It is based on the NOAEL of 50 mg/kg/day from the rat combi ned chronic toxicity/ carcinogenicity study, the lowest NOAEL observed in any of the ch ronic studies. A 100-fold uncertainty factor to account for interspecies extrapolation (10X) and intraspecies variability (10X) was applied over the selected NOAEL in order to establish the RfD.

An extra safety factor (SF) to protect infants and children is not needed based on the following considerations:

a) the toxicity data showed no increase in susceptibility in fetuses and pups with in-utero and post-natal exposure; b) t he dietary food exposure assessment was done with tolerance-level residues and 100% crop treated for all commodities, which results in very high-end estimates of dietary exposure; c) the drinking water assessment was based on values generated by models which are designed to provide conservative, high-end estimates of water concentrations; d) exposures due to recreational activiti es are based on default EPA assumptions that result in high-end estimates of exposure.

A DEEM chronic exposure analysis was conduct ed using the tolerance levels for wheat

-17-grain and meat commodities and assuming 100% of crops treated with The estimated exposures to US-populati on and relevant sensitive sub-population groups were all at least 3 orders of magnit ude below the level of the RfD (< 1% RfD).

2. From Potable Water

Drinking water estimated concentrations were estimated with the SCI-GROW model for ground water and with the Index Reservoir model for surface water. The set of assumptions included the maximum seasonal use rate of 0.11 lb a.e./A, K
oc of 1.05 and a half-life of 38.7 days. does not have an acute RfD established; therefore, an acute assessment is not needed for drinki ng water. A chronic exposure assessment considering the highest chronic concentrations from surface drinking water has shown levels of exposure which are four or ders of magnitude below the RfD of 0.5 mg/kg-bw/day, both for adults and children 1-6 years of age.

3. For Non-Dietary Uses

At this time, there are no requested uses for that are considered home uses and neither handler nor post-application residential exposures from uses around home are expected to occur. However, the use on campgrounds and other recreation areas to control vegetation has the potential to result in short-term post-application incidental oral exposures for infants and ch ildren via hand-to mouth transfer of residues and ingestion of contaminated grass and soil. Post-application exposure via inhalation is not expected to occur.

Short-term residential exposure to children wit h 15 kg body-weight from the three routes mentioned above was estimated using the HED Draft Standard O perating Procedures (SOP's) for Residential Exposure Assessment s (12/18/97) and the Revisions to the Standard Operating Procedures (SOP's) for Residential Exposure Assessment (Science advisory Council for Exposure Policy 12, Revi sed February 22, 2001) for Hand-to-Mouth Transfer, Ingestion of Turfgrass and Ingestion of Soil, from uses on lawn broadcast application. The lowest MOE was 150,000 for this tier-I post-application residential assessment and it corresponds to child ren exposed via the hand-to-mouth route.

AGGREGATE RISK CONCLUSIONS

Since the only source of residential exposur e would result from oral exposure, an aggregate exposure assessment was performed adding the estimated chronic dietary exposure to the estimated short-term oral residential exposure. Totaling the two oral exposure estimates gives a combined potential level of 0.0033 mg/kg/day, for the highest exposed group, children 1-2 years of age. The margin of exposure (MOE) associated with this Tier I exposure estimate is 32,000 and it is much above the acceptable limit (MOE = 100). EPA thus concludes that there is reasonable certainty that no harm will come from aggregate exposure to residues.

-18-CUMULATIVE EXPOSURE TO SUBSTA NCES WITH COMMON MECHANISM OF TOXICITY

Unlike other pesticides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding for and any other substances. Furthermore, does not appear to have a toxic metabolite that is produced by other substances. For the time being, EPA has assumed that does not have 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 such chemicals, see the policy statements released by the Office for Pesticides 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/

OCCUPATIONAL EXPOSURE

Based on labeled uses, the occupational exposure is expected to be short- to intermediate-term and no long-term exposure is expected. The application of to control weeds in wheat, rangeland, pastures, non-cropland areas and natural recreation areas is recommended by usi ng broadcast treatment with ground and aerial equipment on wheat and also hand-spray and s pot treatments for all other uses.

Based on the available toxicological informa tion, dermal exposures do not result in any adverse systemic effect; therefore, derma l exposures were not included into the estimation of occupational risk to worker s. Short- and intermediate-term oral and inhalation exposures are being regulat ed based on the effects seen in the developmental rabbit toxicity study, wh ich showed a NOAEL of 104 mg/kg/day.

The highest potential exposure was estima ted to Mixer-Loaders working on aerial applications of 0.11 lb ae/A, for up to 1200 acres applied per day. The corresponding MOE is 40,000.

SUMMARY OF DATA GAPS

No major data gaps have been identified with the registrant-subm itted data, although uncertainties were noted in the determinations of soil half-life, chronic effects on birds and effects upon cyanobacteria.

1. Submit com p leted enforcem ent m e thod of analysis to show that analytical m e thod differentiates between picloram and clopyralid.

-19-2. The analytical m e thod m u st be submitted to EPA Fort Meade Laboratory for validation.

3, Submit storage stability data f o r grass f o rage and hay ref l ecting up to approxim a tely 15

m onths of frozen storage.

4. Submit a repeated Aerobic Soil Metabolism Study (EPA Guidelines No. 162-1).

5. Submit a repeated Avian Reproduction study in bobwhite quail (EPA Guideline No. 71- 4(a).

6. Submit a repeated Tier II Aquatic Plant Growth: Blue-Green Algae, Anabaena flos aquae (EPA Guideline No. 123-2).

PUBLIC INTEREST FINDING

is a Reduced Risk herbicide that provides reliable control of a broad spectrum of difficult-to control noxious weeds and invasive plants on rangeland and pastures, rights-of-way, and wildlife habitat areas

. is particularly effective for the control of tropical soda apple, musk thistle, Canada thistle, spotted knapweed, diffuse knapweed, yellow starthistle and Russian knapweed. has a favorable human health toxicity profile when co mpared to the registered alternatives for these use sites and will be applied at a lower rate. Its residual action should alleviate the need for repeat applications, resulting in a reduction in the amount of herbicides applied to the environment for the control of these weeds. has been determined to be practically non-toxic to non-tar get animals at the registered application rates, compared to the alternatives, and is less likely to impact both terrestrial and aquatic plants.

GOVERNMENT PERFORMANCE AND RESULTS ACT (GPRA) Registration of will meet the obj ectives of GRPA title 3.1.1 by assuring new pesticides that enter the market are safe for humans and the environment and title 4.1.2 by reducing environment al exposure to herbicides.

CONTACT PERSON AT EPA Joanne Miller, Project Manager, Team 23 Herbicide Branch Registration division (7505C)

E-Mail Address: miller.joanne@epamail.epa.gov

Mailing Address:

-20-US Environmental Protection agency Office of Pesticide Programs (7505C) Ariel Rios building 1200 Pennsylvania Ave., N.W. Washington, D.C. 20460

Office Location and Telephone Number Room 241, Crystal Mall building #2 1801 south Bell Street Arlington, VA 22202 (703) 305-6224

Disclaimer: The information presented in this Pesticide Fact Sheet is for informational purposes only and may not be used to fill dat a requirements for pesticide registration and reregistration.

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