# Registration of Indaziflam on Residential and Commercial Areas, (Lawns, Ornamentals, and Hardscapes) Turf, Nurseries, and Forestry

July 22, 2010

U.S. Environmental Protection Agency Office of Pesticide Programs Registration DivisionRegistration of Indaziflam on Residential Areas (Lawns, Ornamentals, and Hardscapes) Turf, Nurseries, and Forestry

Regulatory Rationale

The Agency is conditionally granting the first registrations of the active ingredient, indaziflam, formulated as a technical product, a manufacturing use product, a nd seven end use products. It is for application to residential and commercial areas (lawns, ornamentals, and hardscapes including patios, walkways, etc.), turf (parks, ceme teries, golf courses, sod farms, sports fields, and commercial lawns), field gr own ornamentals and Christmas trees, commercial nursery and landscape plantings, and forestry. Indaziflam is a selective he rbicide providing pre-emergence and post-emergence (when indaziflam is fo rmulated with 2,4-D, dicamba, mecoprop, and penoxsulam) control of annual grasses and broadl eaf weeds. Pending proposed use sites (not covered under this Agency Action) include citr us, stone, and pome fru it, grapes, tree nuts, pistachios, and olives.

I. Chemical Information

Chemical Name: Indaziflam; N-[(1R,2S)-2,3-dihydro-2,6-di methyl-1H-inden-1-yl]-6-[(1RS)-1- fluoroethyl]-1,3,5-triazine-2,4-diamine

EPA PC Code: 080818

Chemical Abstracts Service (CAS) Number: 950782-86-2

Mode of Action: Indaziflam controls weeds by inhibiti ng cellulose biosynth esis (CB Inhibitor)

Registrant: Bayer Environmental Science and Bayer Advanced

Products: Indaziflam is being registered as EPA Reg. 432-1501 BCS-AA10717 Technical Herbicide (containing 95.8% indaziflam) and EPA Reg. 432-1498 BCS-AA10717 2% MUP Herbicide (containing 2.0% indazi flam). Indaziflam is for use by commercial applicators (formulated in water soluble bags and added to tu rf fertilizer). These registrations include EPA Reg. 432-1499 BCS-AA10717 20WSP Herbicide (con taining 20.0% indaziflam), EPA Reg.

432-1495 BCS-AA10717 0.0142% Plus Turf Fert ilizer Herbicid e (containing 0.0142% indaziflam), EPA Reg. 432- 1496 BCS-AA10717 0.0213% Plus Turf Fertilizer Herbicide (containing 0.0213% indaziflam), and EPA Reg. 432-1497 BCS-AA10717 0.0284% Plus Turf Fertilizer Herbicide (con taining 0.0284% indaziflam). Indazifl am is also for residential use by non-commercial applicators (formulated as a spra y and a granule). Thes e registrations include EPA Reg. 72155-89 Lawn 3FL Herbicide Concen trate / Ready to Spray (containing 0.25% indaziflam), EPA Reg. 72155-90 Lawn 3FL He rbicide Ready to Use (containing 0.0031% indaziflam) and EPA Reg.72155-91 Lawn 3F L Herbicide Granule (containing 0.05% indaziflam).

3Indaziflam may be applied through a variety of application methods ranging from broadcast equipment to hand held equipment (aerial applica tion is proposed for the food uses but is not covered by this action). Maximum annual appl ication rates range from 0.089 to 0.134 lbs. ai/acre/year.

II. Human Health Risk

A summary of the human health effects and risk of indaziflam as assessed in the Agency document entitled “Indaziflam: Human Health Risk Assessment for Use of Indaziflam on Turf, Golf Courses, Sod Farms, Christmas Tree Farms, Non-Crop Areas and Forestry” is provided

below.

The toxicology database is considered adequate for selecting toxicity endpoints for risk assessment. The scientific quality is relatively high, and the toxici ty is well-characterized for all types of effects, including pot ential developmental, reproduc tive, immunologic and neurologic toxicity. At this time the databa se is considered complete.

Indaziflam has low acute toxicity via the oral (T oxicity Category III), dermal (Toxicity Category III) and inhalation (Toxicity Categor y IV) routes of exposure. Inda ziflam is not irritating to the eye or skin (Toxicity Category IV) and is not a dermal sensitizer.

The nervous system is a target for indaziflam in rats and dogs. Degenerative neuropathology of the brain, spinal cord and scia tic nerve was reported in the dog following both subchronic and chronic oral exposure. Neuropathology in the dog was the most sensitive effect and was selected as the endpoint for all exposure s cenarios involving repeated exposur e. In the rat, histopathology

of the brain and pituitary pars nervosa was observed following chroni c exposure. Clinical signs of neurotoxicity were observed in both species in several stud ies, which included rat adult and developmental neurotoxicity studies. Decreas ed motor activity observed in the rat acute neurotoxicity study was selected as the appropriate endpoint for acute oral toxicity.

Degenerative renal effects were observed in the rat and mouse following chronic exposure. Liver hypertrophy was observed in rats, and fe males showed liver hi stopathology. Thyroid

effects were observed in male rats followi ng subchronic and chronic exposure but were considered secondary to liver stimulation and o ccurred at significantly hi gher doses than those selected for risk assessment (15-fold or greate r), and therefore are not considered to be of concern for pre- and/or postn atal development. Other e ffects observed following chronic exposure were an increased incidenc e of atrophied or small seminal vesicles in male rats and in female mice, an incidence of stomach erosions , and blood-filled ovarian cysts. Decreased body weight gains were generally observed in the av ailable studies. No systemic toxicity was observed in a 28-day dermal t oxicity study in the rat.

In the rat developmental toxicity study, decrease d fetal weight was observed in the presence of maternal effects that included decreased body weight and clinical signs of toxicity. No developmental effects were observed in rabbits up to maternally toxic dose levels. Decreased pup weight and delays in sexual maturation (preputial separation in males and vaginal patency in females) were observed in the rat two-generatio n reproductive toxicity st udy, along with clinical

4signs of toxicity, at a dose causing parental toxic ity that included clinic al signs and decreased weight gain. In the developmental neurotox icity study, transiently de creased motor activity (PND 21 only) in male offspring was observed and wa s considered a potential neurotoxic effect.

It was observed at a dose that also caused clin ical signs of neurotoxic ity along with decreased body weight in maternal animals.

There was no evidence of carcinogenicity obser ved in the two-year dietary rat or mouse carcinogenicity bioassays and no evidence of genotoxi city in mutagenicity studies (reverse gene mutation in bacteria, forward gene mutation in mammalian cells) or in vitro and in vivo chromosomal aberration assays. Based on the lack of evidence of carcinogenicity or genotoxicity, the Agency classified indaziflam as “Not likely to be carcinogenic to humans.”

The observed neurotoxic effects in rats and dogs serve as the basi s for the risk assessment, since all endpoints were associated with the neurotox ic effects observed in the animal studies. The proposed use pattern is expected to result in derm al, inhalation and incident al oral exposures of

short- and intermediate-term dura tions; therefore, long-term exposur e and risk were not assessed.

A. Toxicological End Points and Doses Us ed in the Human Health Risk Assessment

1. Acute : EPA established an acute reference dose (a RfD) and an Acute Population Adjusted Dose (aPAD) for indaziflam of 0.50 mg/kg body wt, based on the “No Observable Effects Level” (NOAEL) of 50 mg/kg body weight from th e acute neurotoxicity study in rats and an uncertainty factor of 100. In this study, decreased motor and locomotor activity was observed in

females at the “lowest observed adverse effect level” (LOAEL) of 100 mg/kg body wt.

2. Chronic Dietary : EPA established a chronic reference dose (cRfD) and a Chronic Population Adjusted Dose (cPAD) for indaziflam of 0.02 mg/kg body wt/day, based on the NOAEL of 2.0 mg/kg body wt/day from the chronic toxicity study in dogs and an uncertainty factor of 100. In this study, nerve fiber degeneration in the brain, sp inal cord and sciatic ne rve was observed at the LOAEL of 6/7 (M/F) mg/kg body wt/day.

3. Short- and Intermediate-Term Incide ntal Oral, Dermal and Inhalation: The same endpoint (toxic effect) and dose (NOAEL) were selected for assessing incidental oral, dermal and inhalation exposure. EPA selected the NOAEL of 7.5 mg/kg body wt/day from the subchronic toxicity study in dogs based on brain, spinal cord and sciatic nerve degenerative lesions observed at the LOAEL of 15 mg/kg body wt/day. Sin ce the dermal and inhalation endpoints were selected from an oral study, a dermal absorptio n factor of 7.3% and an inhalation absorption

factor of 100% were used in th e relevant exposure assessments.

For all of these routes of exposure, EPA’s Le vel of Concern (LOC) is a Margin of Exposure (MOE; calculated as the NOAEL ÷ exposure) of 100; the LOC is based on the uncertainty factor of 100, and MOEs less than 100 repres ent a potential ri sk concern.

4. Cancer : EPA has classified indaziflam as “Not Likely to be Carcinogenic to Humans” based

on the lack of treatment-related tumors in the two-year rat and mouse bioassays. There was no evidence of mutagenicity in genotoxicity studie s, including a reverse gene mutation study in

5bacteria, a forward gene mutation study in mammalian cells, and in vitro and in vivo chromosomal aberration assays.

B. FQPA Safety Factor

Although there are no food uses associated with this decision, there are food uses pending review, and, therefore, EPA evaluated the pot ential impact of the decision on infants and children. The Agency determined that reliable da ta show that it would be safe to reduce the FQPA safety factor for infants and child ren to 1X based on the following findings:

• The toxicity database for indaziflam is c onsidered complete and includes acceptable developmental toxicity studies in rats and rabbits, a two-ge neration reproductive toxicity study in rats, a developmental neurotoxicity in rats, acute and subc hronic neurotoxicity screening studies in rats, and an immunotoxicity study.

• Although indaziflam is a neurotoxic chem ical, there is no evidence of increased qualitative or quantitative suscep tibility of offspring to neur otoxic effects in any of the available studies, including a developmenta l neurotoxicity study. Therefore, an additional uncertainty factor to acco unt for neurotoxicity is unnecessary.

• There is no evidence that indaziflam results in increased pre- or postn atal susceptibility of rats or rabbits in the prenatal developmen tal studies or of rats in the 2–generation reproduction study. Effects on fetuses and offs pring in these studies were observed at doses that also resulted in parental toxici ty. The endpoints selected for risk assessment are protective of potential de velopmental effects.

• There are no residual uncertainties identifie d in the exposure databases. EPA made conservative (protective) assumptions in th e ground and surface water modeling used to assess exposure to indaziflam in drinking water. EPA used similarly conservative assumptions to assess post-application expos ure of children including incidental oral exposure of toddlers. These assessments wi ll not underestimate th e exposure and risks posed by indaziflam.

C. Cumulative Effects

Indaziflam and its metabolite fluoroethyldiami notriazine (FDAT) contain a triazine moiety

within their chemical structures. Several triazine herbicides we re determined by EPA to have a common mechanism of toxicity based on their ability to disrupt the hypothalamic-pituitarygonadal axis (US EPA

, 2002). The triazine common m echanism group (TCMG) includes atrazine, simazine, propazine, a nd the metabolites desethyl-s-a trazine (DEA), deisopropyl-satrazine (DIA), and diaminochlorotriazine (DAC T). Indaziflam and its metabolite FDAT were considered for incorporation into the TCMG by EPA based on structure; indaziflam, FDAT, and the TCMG members contain a common triazine moiety. However, EPA determined that it would not be appropriate to include indaziflam and FDAT in the TCMG for the following reasons: 1) The structure of indaziflam and FDAT are unique in that they contain a fluoroethyl group at the 2-position of the triazine ring, whereas the TCMG members contain a chlorine substituent at the 2-position of the triazine ring and; 2) Indazi flam and FDAT do not elicit the same toxicological responses shared by the TC MG members. The TCMG members cause an increase in mammary gland tumors in rats and multiple developmental effects such as

6attenuation of the luteinizing hormone surge, altered pregnancy outcome, and delayed preputial separation. Although delayed sexu al maturation was observed in the rat reproductive toxicity study, the effects occurred only at th e highest dose. None of the ot her effects associated with the

TCMG members were observed in the carcinogenicity, developmenta l, or reproductive guideline studies for indaziflam. In a non-guideline study, FDAT delayed vaginal patency in a dosedependent manner. However, none of the other characteristic developmental effects of the TCMG members were observed, and this effect only occurred at higher doses compared to

DACT.

Therefore, unlike other pesticides for which EPA has followed a cumulative risk approach based

on a common mechanism of toxici ty, EPA found that neither i ndaziflam nor its metabolite FDAT, have a common mechanism of toxicity, w ith any other substances, and indaziflam does not appear to produce a toxic meta bolite produced by other substances.

D. Aggregate Risk Assessment

1. Drinking Water Risk :

A screening level drinking water exposure ri sk assessment was conducted using the Dietary Exposure Evaluation Model Database (DEEM-FCID TM ) and estimated drinking water concentrations (EDWCs) generated using the Pe sticide Root Zone Model /Exposure Analysis Modeling System (PRZM/EXAMS) and Screening Concentrati on in Ground Water (SCIGROW) model.

Dietary exposure to indaziflam from drinking water will occ upy 3.0% of the aPAD and 9.0% of the cPAD for infants, less than 1 year old (the population subg roup with the highest estimated exposure to indaziflam). Therefore, acute and chronic drinking water risk estimates are not of concern because the percentage of the aPAD and cPAD are below the Agency’s Level of Concern (100%).

2. Residential Risk :

There is a potential for exposure of homeowne rs applying products co ntaining indaziflam on home lawns. There is also a potential for pos t-application exposure of adults and children entering lawn and recreation ar eas, including golf courses, which have been treated with indaziflam. Indaziflam post-application inhalatio n exposures are expected to be negligible due to its low vapor pressure, low app lication rates, and the types of application equipment used (i.e., hand-held equipment that is not likely to gene rate a vapor). Therefore, a quantitative postapplication inhalation exposure assess ment was not considered necessary.

EPA assessed the following residential exposure scenarios:

• short -term dermal and inhalation exposures of residential handlers us ing various types of application equipment and formulation type s on the proposed residential use sites;

• short -term post-application dermal exposures of adults and children entering treated turf areas; and

7• short-term postapplication incide ntal oral exposures of childre n from contact with treated turfgrass.

Since the doses and endpoints selected to assess short- and intermediate-term exposures are the same, a quantitative intermediate-term assessment was not completed; however, the short-term risk assessments are protective of intermediate -term risks. For residential and occupational exposure, the Agency uses the term Margin of Exposure (MOE) to refer to the risk associated with the exposure estimate. The MOE is define d as the dose, usually the No Observed Adverse Effects Level (NOAEL), divided by the estimated human exposure. An MOE of 100 means that

the estimated level of human e xposure is 100 times lower than th e highest dose that produced no

adverse effects in the relevant toxicology study. The greater the MOE, the lower the risk. An MOE of 100 or greate r indicates there are no risks of concern.

Estimated short -term residential handler MOEs (combined dermal and inhalation exposures) range from 3,000 to 510,000. Estimated MOEs for s hort-term post-application dermal exposures of adults entering treated lawn areas range fr om 4,700 to 10,000. The estimated MOE for golfers playing on treated turf is 90,000. The estimated combined MOE for short-term postapplication exposures of children (including dermal and in cidental oral exposur es) is 1,800. Since all

estimated MOEs are well above 100, they are not of concern.

3. Aggregate Risk :

In the absence of food uses, an aggregate risk assessment was not needed for indaziflam. However, the screening-level combined exposures from drinking water and residential settings result in estimated MOEs of 1,100 for children and 1,700 for adults. Therefore, combined exposure and risk from drinking water and residential sources are not of concern.

E. Occupational Risk Assessment

Short- and intermediate-term occupational handl er and postapplication exposures are possible based on the use pattern. However, since the same endpoint and dose we re selected for both short- and intermediate-term risk assessment, intermediate-term exposures were not assessed. Short-term exposure and risk estimates are protective of corres ponding intermediate-term exposure and risk.

1. Handler Exposure and Risk :

EPA assessed short-term dermal and inhalation exposures of occupational handlers. Combined inhalation/dermal MOEs for occupational ha ndlers range from 100 to 840,000. Since all MOEs are greater than or equal to 100, short -t erm risks for handlers are not of concern.

2. Occupational Postapplic ation Exposure and Risk :

Occupational post-application de rmal MOEs ranged from 1,400 to 45,000 and, therefore, are not of concern. Post-application inhala tion exposures to indaziflam are expected to be negligible due to indaziflam’s low vapor pressure and low appli cation rates; in addition, with the exception of

8forestry applications, the types of application equipment used will minimize the formation of a vapor or fine aerosol that would lead to significant inhalation exposure.

III. Environmental Risk

A summary of the environmental fate and ecological effects and risks of indaziflam as assessed in the Agency document titled “Environmental Fa te and Ecological Risk Assessment for the Registration of Indaziflam” is provided below.

A. Environmental Fate

Indaziflam is expected to be moderately mobile to mobile in the soil (Koc < 1000 mL/g oc), moderately persistent to persiste nt in aerobic soil (hal f-lives > 150 days), pers istent in anaerobic soil (stable), and persistent in aerobic (half- lives > 200 days) and anaer obic (stable) aquatic environments. Indaziflam is subject to aqueous photolysis in clear shal low waters (half-life < 5 days). Indaziflam is not volatile and therefore, is not likely to be tr ansported via atmospheric processes following application. It is a weak acid and is moderately soluble at environmental pH values. Indaziflam dissipates in the envir onment primarily through bi otic degradation and leaching. Indaziflam degradates are more mobile than the parent (K

oc < 100 mL/g oc), and were detected in field studies at the deepest depths sampled (105-120 cm). The degradate FDAT is mobile to highly mobile (K

oc ranged from 10 – 50 mL/g oc) and has the potential to leach to the ground water.

The major transformation products resulting from the environmental degradation of indaziflam are: triazine-indanone; indazifl am-carboxylic acid; indaziflam- hydroxyethyl; indaziflam-olefin; fluoroethyldiaminotriazine; and fluoroethyltriazinanedione. Th e toxicity data show that indaziflam-olefin and indaziflam-hydroxyethyl are of similar toxicity to the technical gradeactive ingredient (TGAI), based on the most sensitive taxa tested, while indaziflamhydroxyethyl, FDAT, and triazine in danone demonstrate less toxicity than that of the parent. Aquatic exposure estimates are based on a total to xic residue approach of indaziflam + residues of concern (two major photodegr adates: indaziflam-olefin a nd indaziflam-hydroxyethyl). Terrestrial exposure estimates are based on the resi due levels of indaziflam alone. Data are not generally available for screening level assessments to assess the terrestri al exposure and effects of degradates, as is the case for the assessmen t of indaziflam. The conservative 35-day foliar dissipation half-life used in the terrestrial modeling may account for the formation and toxicity of the degradates (assuming the degradates are not any more toxic than the pare nt). Any effects of the degradates to terrestrial plants that might occur over a 21 day time period would be captured by the nature of the terrestrial plant studies c onducted on indaziflam’s formulated products. Bioaccumulation is not expected for indaziflam.

To address concerns with the potential leach ing of indaziflam that may result from the persistence and mobility described above, labels will be required to have language including surface and ground water advisories that stress the potential of runoff after treatment and descriptions of conditions that may promote leac hing to groundwater. Required label language is described more fully under “Regulatory Decision”, below.

9B. Ecological Risk

Ecological risk characterization in tegrates the results of the e xposure and ecotoxicity data to

evaluate the likelihood of adverse ecological effects. The means of integrating the results of exposure and ecotoxicity data is called the quo tient method. For this method, risk quotients (RQs) are calculated by dividing exposure es timates by ecotoxicity values, both acute and chronic (RQ = Exposure/Toxicity). RQs are then compared to EPA's levels of concern (LOCs). The LOCs are criteria used by the Agency to indicat e potential risk to nont arget organisms. The criteria indicate whether a pesticide, when used as directed, has the potential to cause adverse effects to nontarget organisms.

The ecotoxicity endpoints derived from the results of short-term laborator y studies that assess acute effects are: (1) LC 50 (Lethal Concentration at which 50% of treated organisms die, fish and birds); (2) LD 50 (Lethal Dose at which 50% of treated or ganisms die, birds and mammals); (3)

EC 50 (Environmental Concentration at which 50% of treated organisms die, aquatic plants and aquatic invertebrates) and; (4) EC 25 (Environmental Concentration at which 25% of treated organisms die, terrestrial plants ). The endpoints derived from th e results of long-term laboratory

studies that assess chronic e ffects are the NOAEL and Lowest Observed Adverse Effect Concentration (LOAEL) for birds and mammals a nd No Observed Adverse Effect Concentration (NOAEC) and the Lowest Observed Adverse Effect Concentration (LOAEC) for fish and aquatic invertebrates. Risk presump tions along with the corresponding RQs and LOCs are shown in the

table below.

Risk Presumptions for Non-target Organisms Risk Presumption RQ LOC

Terrestrial Animals

Acute High Risk EEC * /LC50 or LD50/sqft2 or LD50/day3 ≥ 0.5

Acute Restricted Use EEC/LC50 or LD50/sqft2 or LD50/day (or LD50 < 50 mg/kg) ≥ 0.2

Acute Endangered Species EEC /LC50 or LD50/sqft2 or LD50/day ≥ 0.1

Chronic Risk EEC/NOAEL ≥ 1

Aquatic Animals

Acute High Risk EEC/LC50 or EC50 ≥ 0.5

Acute Restricted Use EEC/LC50 or EC50 ≥ 0.1

Acute Endangered Species EEC/LC50 or EC50 ≥ 0.05

Chronic Risk EEC/NOAEC ≥ 1

Terrestrial and Semi-Aquatic Plants

Acute High Risk EEC/EC25 ≥ 1

Acute Endangered Spec ies EEC/EC50 or NOAEC ≥ 1

10Aquatic Plants

Acute High Risk EEC/EC50 ≥ 1

Acute Endangered Spec ies EEC/EC50 or NOAEC ≥ 1

* EEC = Estimated environmental concentration

The calculated risk quotients represent a screening level assessment. Screening level assessments are based on conservative assumptions. For example, screening level assessments always assume the maximum labeled rate, the maxi mum number of applications, and the shortest treatment interval between applications.

1. Aquatic Organisms

Indaziflam is highly toxic (EC 50 = 0.1 – 1 mg a.i./L) to freshw ater and estuarine/marine fish, moderately toxic (EC 50 = 1 -10 mg a.i./L) to highly toxic (EC 50 = 0.1 – 1 mg a.i./L) to estuarine invertebrates, and slightly toxic (EC 50 = 10 - 100 mg a.i./L) to moderately toxic (EC 50 = 1 -10 mg a.i./L) to freshwater invertebrate s on an acute exposure basis. Ho wever, due to the nature of the uses and indaziflam’s susceptibility to a queous photolysis, exposure to freshwater and estuarine/marine fish and invertebrates is expect ed to be limited. All RQs for freshwater fish, aquatic-phase amphibians, and freshwater invert ebrates are below the LOC for acute and chronic risk to listed species (threatened and endangered species under the Endangered Species Act) and non-listed species. All RQs for estuarine and mari ne fish and invertebrates are below the LOC for acute risk to listed and non-listed species.

Chronic data is unavailable to a ssess chronic effects on esturine/m aine fish and invertebrates. Accordingly, risk to this taxon was presumed in the risk estimation. An estimate of the chronic endpoint for estuarine/marine fish is a NOAEC of 578 μg tota l ai/L and RQs < 0.01. Based on this extrapolation, chroni c risk to estuarine/marine fish is not expected. Indaziflam’s limited solubility under realistic condi tions will likely limit chronic effects to estuarine/marine invertebrates. However, due to the lack of chronic effects data for estuarine/marine invertebrates, the Agency presumes that indaziflam is toxic to invertebrates for chronic exposure.

Chronic effects studies for invertebrates ar e required as a condition of registration.

As is common with many herbicides, indaziflam is toxic to nonvascular and vascular aquatic plants. The LOC was exceeded for aquatic vascular plants (see page 71-72 of the Environmental Fate and Ecological Risk Assessment; RQ = 7-101) and aquatic vascular and non-vascular plants listed under the Endangered Species Act (discussed further in the document under Endangered Species Act). To address and mitigate risks to non-target aquatic and semi-aquatic plants, label language will be required and is described mo re fully under “Regulatory Decision”, below.

2. Terrestrial Organisms

Indaziflam is practically nontoxic (LD 50 /LC 50 > 2,000 mg a.i./L) to birds on both an acute oral and subacute dietary exposure basi s. As a minimum level of risk, none of the RQs for any use of indaziflam exceeded the Agency’s chronic risk to birds LOC of 1.0. However, the maximum

direct chronic risk to birds is unknown and can no t be determined based on the available data.

11For chronic studies, treatment-related effects on a dult female weight gain, adult male weight gain, and adult food consumption were observed in avian reproduction studies using the mallard duck. Due to the lack of data, it is presumed that indaziflam is toxic to birds for chronic exposure. A secondary study on th e reproductive effects in the ma llard duck is required as a condition of registration. Indaziflam is practically non-toxic (LD 50 > 2,000 mg a.i./L) to mammals on an acute and chronic exposure basis. Indaziflam is pract ically nontoxic to honey bees. Affects to body weight were observ ed to earthworms from a 14-day study at concentrations of 562-1000 mg a.i/kg dw soil. An estimate of the expected concentration of

indaziflam in real world soil conditions is 800 times smaller than the most sensitive effects endpoint from earthworm toxicity studies. Therefore, the potentia l for risk to earthworms from exposure to indaziflam in soil is not expected.

As is expected with herbicides, terrestrial plants are sensitive to indaziflam. The Agency’s LOC was exceeded for monocots and dicots (see page 75 of the Environmental Fate and Ecological Risk Assessment; spray drift RQ = 1-11, dry area RQ = 2-23, and semi-aquatic area RQ = 11- 125) and listed terrestrial plants under the Enda ngered Species Act (discussed further in the document under Endangered Species Act). To addr ess and mitigate risks to non-target terrestrial plants, label language will be re quired and is described more fu lly under “Regulatory Decision”,

below.

IV. Regulatory Decision

The Agency is conditionally registering a tech nical product, a manufactur ing use product, and seven end use products to be used on residential and commercial areas (lawns, ornamentals, and hardscapes including patios, walkways, etc.), turf (parks, cemeteries, golf courses, sod farms, sports fields, and commercial la wns), field grown ornamentals a nd Christmas trees, commercial nursery and landscape plantings , and forestry uses.

As required by FIFRA, the Agency published a noti ce of receipt (NOR) of applications in the Federal Register (January 27, 2010) to register pesticide pro ducts containing the new active ingredient, indaziflam. No comments were received.

On June 1, 2010, the Agency posted the proposed decision document for indaziflam entitled “Proposed Registration of Indaziflam on Re sidential and Commercial Areas, (Lawns, Ornamentals, and Hardscapes) Turf, Nurseries, a nd Forestry”, the associated risk assessments, and the proposed labels in docket ID nu mber EPA-HQ-OPP-2009-0636. No comments on the proposed decision were submitted to the docket.

A. Data Requirements

The human health risk assessment concluded that the database is complete and adequate for a dietary, residential, and occupational assessment. The environmental fate and effects review concluded that the database is adequate for a sc reening level assessment. However, because of uncertainty regarding chronic risk to birds and estuarine and mari ne invertebrates, the Agency has determined additional data requirements ar e required to better characterize risk. These studies are required as a condition of the registration of indaziflam:

121. An additional avian reproduction study on Mallard duck (OPPTS 850.2300) None of the RQs for any proposed use of indaziflam exceeded the Agency’s chronic risk to birds LOC of 1.0. However, current data on mallard duck were inadequate to derive a

definitive NOAEC or make a definitive determ ination of risk. A second avian reproduction study on mallard duck would reduce uncertainty and obviate the need to presume risk to this

taxon.

2. An estuarine/marine invertebrate life cycle toxicity study (OPPTS 850.1350) Indaziflam’s limited solubility under realistic conditions will likely limit chronic effects to estuarine/marine invertebrates. However, chro nic data are needed to confirm this supposition and fully evaluate risks to estuarine/marine invertebrates.

B. Label Requirements

In order to mitigate risks to non-target organisms such as plants, label language is required that is intended to keep the pesticide on the intended tr eatment area, thereby reducing the potential for exposure to non-target plants and animals. For example, buffer strips and spray drift management language are required on the labeling for EPA Reg. 432-1499 BCS-AA10717 20WSP Herbicide that advises users of appli cator responsibilities a nd requires specific techniques to reduce the possibili ty of spray drift. In additio n, surface water advisories, intended to reduce run-off of the pesticide into aqua tic environments, are required on all labeling.

EPA has made minor changes to the label language specified in the proposed decision document. Explanations for these changes are provided in italics below the new language.

The specific label language required for inda ziflam products is presented below:

1. All End-Use Product Labels

“Ground Water Advisory: This pesticide has properties and characteristics associated with chemicals detected in ground water. This chemical may leach into ground wate r if used in areas where soils are permeable, particularly where the wa ter table is shallow.”

“Surface Water Advisory: This pesticide may impact surface water quality due to runoff of rain water. This is especially true for poorly draining soils and soils with shal low ground water. This pr oduct is classified as having a high potential for reaching surface water via runoff for several months or more after application.”

“Environmental Hazards: This Product is toxic to fish, aquatic invertebrates, and plants. Do not apply directly to water, or to areas where surface water is present or to inte rtidal areas below the mean water mark. Do not contaminate water when disposing of rinseate or washwater. This product may impact water through spray drift or runoff. Follow directions fo r use to avoid spray drift and runoff. A level

13well maintained vegetative buffer strip between areas to which this pr oduct is applied and surface water features including ponds, streams, and springs will reduce the potential of this product entering water from rainfall runoff. Runoff of this produc t will be reduced by avoiding applications when rainfall is forecasted to occur within 48 hours.”

2. All Manufacturing-Use Product Labels

“Environmental Hazards: This pesticide is toxic to fish, aquatic invert ebrates, and plants. Do not discharge effluent containing this product into lakes, streams, ponds , estuaries, oceans or other waters unless in accordance with the requirements of a Nationa l Pollutant Discharge Elimination System (NPDES) permit and the permitting authority has been notified in writing prior to discharge. Do not discharge effluent containi ng this product into sewer system s without previously notifying the local sewage treatment pl ant authority. For guidance cont act your State Water Board or Regional Office of the EPA.”

The Environmental Hazards section has been revised to be consiste nt with standard label language required for end-use and manufacturing-use products.

3. Requirements for EPA Reg. 72155-89 Lawn 3FL Herbicide Concentrate / Ready to Spray and EPA Reg. 432-1499 BCS-AA10717 20 WSP Herbicide (20% indaziflam)

The proposed use on “hardscapes” will be revised to a spot treatment only to cracks of patios, sidewalks, and driveways.

4. Requirements for commercial -use liquid/WSP formulati on products :EPA Reg. 432-1499 BCS-AA10717 20 WSP Herbicide (20% indaziflam)

“For use on sod farms, golf courses, and non-cr op areas (excluding lawns), do not apply within 25 feet of ponds, lakes, rivers, streams, ditche s, wetlands, and habitat containing aquatic and semi-aquatic plants. For forestry uses, do not apply within 50 feet of ponds, lakes, rivers, streams, ditches, wetlands, and habitat c ontaining aquatic and semi-aquatic plants”

The proposed decision document specified buffers of 25 feet for “turf” an d 50 feet for “all other uses.” The new language further clarifies the area s that EPA considers to have the most risk of run-off into sensiti ve aquatic areas.

“Do Not Apply by Air”.

“Spray Drift Management (General): Spray equipment and weather affect spray drift. Consider all factors when making application

decisions. Where states have mo re stringent regulations, they mu st be observed. Avoiding spray drift is the responsibility of th e applicator or grower. To re duce the potential for drift, the application equipment must be set to apply medi um to large droplets (i.e., ASAE Standard 572) with corresponding spray pressure . Use high flow rate nozzles to apply the highest practical spray volume. With most nozzle types, narrowe r spray angles produce larger droplets. Follow

14the nozzle manufacturer’s directio ns on pressure, orientation, spra y volume, etc., in order to minimize drift and optimize coverage and control.”

“Wind Avoid making applications when spray particles may be carried by air currents to areas where sensitive crops and non-target plants are growing. Do not spray near sensitive plants if wind is gusty, below 2 mph, or in excess of 10 mph and moving in the direction of adjacent areas of sensitive crops or plants. Do not apply dur ing temperature inversions. Always make applications when there is some air movement to determine the direction and distance of possible spray drift.

Local terrain may influence wind patterns; the applicator must be familiar with local conditions and understand how they may impact spray drift. Boom or nozzle shielding can reduce the effects of wind or air currents on drift. Verify that the shields do not interfere with uniform deposition of product prior to application.”

“Temperature Inversion A surface temperature inversion (i.e., increasi ng temperature with increasing altitude) greatly increases the potential for drift. Avoid application when conditi ons are favorable to inversion. Presence of ground fog is a good indicator of a surface temperature inversion.”

“Sensitive Areas Sensitive areas to this product are defined as bodies of water (ponds, lakes, rivers, streams, and ditches containing casual water), habitats of endangered species and non-labelled agricultural crop areas. Applicators must take all precautions necessary to keep spray drift from reaching

sensitive areas.”

The originally proposed language specified “non -target plants, includ ing agricultural crop areas” in the definition of “s ensitive areas.” EPA has concl uded that the term“non-target plants” is overly broad and would severely restrict the use of this product in agricultural areas. In addition, the proposed language included a require ment to make applications when “wind is blowing away from sensitive areas.” This require ment would unintentially eliminate uses where sensitive areas are adjacent on all sides of the application site. EPA has determined that a winddirection restriction is unn ecessary, since the required buf fers are adequate mitigation to prevent spray drift onto sensitive areas.

“Spray Drift Management (Golf Course s; Residential and Commercial Lawns): Set the boom and make applications at the lowest height that safely permits uniform coverage of the soil and minimizes droplet evaporation. Fo r use on golf courses and commercial lawns, the boom height must be no higher than 3 feet above the ground and nozzl e tips must be set to spray out medium to very coarse spray droplets. App lications to residential lawns must be made by equipment that maintains coarse sp ray droplets (to reduce drift).”

EPA has increased the maximum boom height from 2 to 3 feet to correspond with realistic application equipment limitations.

15“Spray Drift Management (Ornamentals): For deciduous ornamental plants, the spray must be directed at the base of the plant or away from the plant but as not to come in contact with the foliage as some leaf malformations or discoloration may occur. Dormant deciduous tr ees are tolerant to indaziflam herbicide.”

“Spray Drift Management (Conifers/Christmas Trees): Conifers including Christmas trees are tolerant to foliar applications of in daziflam. In Christmas tree farm operations, direct the spray to the base of the trees on a band or broa dcast application.”

C. Public Interest

The Agency believes that the registration of inda ziflam is in the public interest (based on

“Review of Public Interest Fi nding Document of Indaziflam (DP# 367092)”, dated November 19, 2009). Indaziflam controls a broad spectrum of weeds, including species which are difficult to eliminate (including blue grass, goose grass, and crab grass). Indaziflam appears to have greater efficacy in controlli ng annual blue grass in turf compared to prodiamine and pendimethalin. Indaziflam has a unique mode of action which is not f ound in other herbicides used for grass weed control and can be used as a tool in herbicide resistant management programs in turf and ornamentals. Indaziflam can be used in combination with other herbicides for a long-term and broader control of grasses and broadleaf weeds. Indaziflam is classified as “not likely to be carcinogenic to humans”. Prodiamine, oxadiazon, and pendimethalin (the major herbicides currently used in the pre-emergence herbicide market in turf weed control) are classified as “likely to be carcinogenic to humans”.

D. Section 3(c)(7)(C) Finding

In accordance with FIFRA 3(c)(7)(C), for the reasons stated above, the Agency believes that the conditional registration of indaziflam will not cause any unreasonable adverse effects on the environment or to human health and is in the pub lic’s interest. Therefor e, the Agency grants these conditional registrations.

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