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 Division 

Registration 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, and seven end use products. It is 

for application to residential and commercial areas (lawns, ornamentals, and hardscapes 

including patios, walkways, etc.), turf (parks, cemeteries, golf courses, sod farms, sports fields, 

and commercial lawns), field grown ornamentals and Christmas trees, commercial nursery and 

landscape plantings, and forestry. Indaziflam is a selective herbicide providing pre-emergence 

and post-emergence (when indaziflam is formulated with 2,4-D, dicamba, mecoprop, and 

penoxsulam) control of annual grasses and broadleaf weeds. Pending proposed use sites (not 

covered under this Agency Action) include citrus, stone, and pome fruit, grapes, tree nuts, 

pistachios, and olives. 

I. Chemical Information 

Chemical Name: Indaziflam; N-[(1R,2S)-2,3-dihydro-2,6-dimethyl-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 inhibiting cellulose biosynthesis (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% indaziflam). Indaziflam is for use by commercial applicators 

(formulated in water soluble bags and added to turf fertilizer). These registrations include EPA 

Reg. 432-1499 BCS-AA10717 20WSP Herbicide (containing 20.0% indaziflam), EPA Reg. 

432-1495 BCS-AA10717 0.0142% Plus Turf Fertilizer Herbicide (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 (containing 0.0284% indaziflam). Indaziflam is also for residential use by 

non-commercial applicators (formulated as a spray and a granule). These registrations include 

EPA Reg. 72155-89 Lawn 3FL Herbicide Concentrate / Ready to Spray (containing 0.25% 

indaziflam), EPA Reg. 72155-90 Lawn 3FL Herbicide Ready to Use (containing 0.0031% 

indaziflam) and EPA Reg.72155-91 Lawn 3FL Herbicide Granule (containing 0.05% 

indaziflam). 

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Indaziflam may be applied through a variety of application methods ranging from broadcast 

equipment to hand held equipment (aerial application is proposed for the food uses but is not 

covered by this action). Maximum annual application 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 toxicity is well-characterized for all 

types of effects, including potential developmental, reproductive, immunologic and neurologic 

toxicity. At this time the database is considered complete. 

Indaziflam has low acute toxicity via the oral (Toxicity Category III), dermal (Toxicity Category 

III) and inhalation (Toxicity Category IV) routes of exposure. Indaziflam 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 sciatic 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 scenarios involving repeated exposure. In the rat, histopathology 

of the brain and pituitary pars nervosa was observed following chronic exposure. Clinical signs 

of neurotoxicity were observed in both species in several studies, which included rat adult and 

developmental neurotoxicity studies. Decreased 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 females showed liver histopathology. Thyroid 

effects were observed in male rats following subchronic and chronic exposure but were 

considered secondary to liver stimulation and occurred at significantly higher doses than those 

selected for risk assessment (15-fold or greater), and therefore are not considered to be of 

concern for pre- and/or postnatal development. Other effects observed following chronic 

exposure were an increased incidence 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 available studies. No systemic toxicity was 

observed in a 28-day dermal toxicity study in the rat. 

In the rat developmental toxicity study, decreased 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-generation reproductive toxicity study, along with clinical 

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signs of toxicity, at a dose causing parental toxicity that included clinical signs and decreased 

weight gain. In the developmental neurotoxicity study, transiently decreased motor activity 

(PND 21 only) in male offspring was observed and was considered a potential neurotoxic effect. 

It was observed at a dose that also caused clinical signs of neurotoxicity along with decreased 

body weight in maternal animals. 

There was no evidence of carcinogenicity observed in the two-year dietary rat or mouse 

carcinogenicity bioassays and no evidence of genotoxicity 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 basis for the risk assessment, since 

all endpoints were associated with the neurotoxic effects observed in the animal studies. The 

proposed use pattern is expected to result in dermal, inhalation and incidental oral exposures of 

short- and intermediate-term durations; therefore, long-term exposure and risk were not assessed. 

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

1. Acute: EPA established an acute reference dose (aRfD) 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 the 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, spinal cord and sciatic nerve was observed at the 

LOAEL of 6/7 (M/F) mg/kg body wt/day. 

3. Short- and Intermediate-Term Incidental 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. Since the dermal and inhalation endpoints were 

selected from an oral study, a dermal absorption factor of 7.3% and an inhalation absorption 

factor of 100% were used in the relevant exposure assessments. 

For all of these routes of exposure, EPA’s Level 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 represent a potential risk 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 studies, including a reverse gene mutation study in 

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bacteria, 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 potential impact of the decision on infants and 

children. The Agency determined that reliable data show that it would be safe to reduce the 

FQPA safety factor for infants and children to 1X based on the following findings: 

• The toxicity database for indaziflam is considered complete and includes acceptable 

developmental toxicity studies in rats and rabbits, a two-generation reproductive toxicity 

study in rats, a developmental neurotoxicity in rats, acute and subchronic neurotoxicity 

screening studies in rats, and an immunotoxicity study. 

• Although indaziflam is a neurotoxic chemical, there is no evidence of increased 

qualitative or quantitative susceptibility of offspring to neurotoxic effects in any of the 

available studies, including a developmental neurotoxicity study. Therefore, an 

additional uncertainty factor to account for neurotoxicity is unnecessary. 

• There is no evidence that indaziflam results in increased pre- or postnatal susceptibility of 

rats or rabbits in the prenatal developmental studies or of rats in the 2–generation 

reproduction study. Effects on fetuses and offspring in these studies were observed at 

doses that also resulted in parental toxicity. The endpoints selected for risk assessment 

are protective of potential developmental effects. 

• There are no residual uncertainties identified in the exposure databases. EPA made 

conservative (protective) assumptions in the ground and surface water modeling used to 

assess exposure to indaziflam in drinking water. EPA used similarly conservative 

assumptions to assess post-application exposure of children including incidental oral 

exposure of toddlers. These assessments will not underestimate the exposure and risks 

posed by indaziflam. 

C. Cumulative Effects 

Indaziflam and its metabolite fluoroethyldiaminotriazine (FDAT) contain a triazine moiety 

within their chemical structures. Several triazine herbicides were 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 mechanism group (TCMG) includes 

atrazine, simazine, propazine, and the metabolites desethyl-s-atrazine (DEA), deisopropyl-satrazine (DIA), and diaminochlorotriazine (DACT). 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) Indaziflam and FDAT do not elicit the 

same toxicological responses shared by the TCMG members. The TCMG members cause an 

increase in mammary gland tumors in rats and multiple developmental effects such as 

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attenuation of the luteinizing hormone surge, altered pregnancy outcome, and delayed preputial 

separation. Although delayed sexual maturation was observed in the rat reproductive toxicity 

study, the effects occurred only at the highest dose. None of the other effects associated with the 

TCMG members were observed in the carcinogenicity, developmental, 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 toxicity, EPA found that neither indaziflam nor its metabolite 

FDAT, have a common mechanism of toxicity, with any other substances, and indaziflam does 

not appear to produce a toxic metabolite produced by other substances. 

D. Aggregate Risk Assessment 

1. Drinking Water Risk: 

A screening level drinking water exposure risk assessment was conducted using the Dietary 

Exposure Evaluation Model Database (DEEM-FCID TM) and estimated drinking water 

concentrations (EDWCs) generated using the Pesticide Root Zone Model /Exposure Analysis 

Modeling System (PRZM/EXAMS) and Screening Concentration in Ground Water (SCIGROW) model. 

Dietary exposure to indaziflam from drinking water will occupy 3.0% of the aPAD and 9.0% of 

the cPAD for infants, less than 1 year old (the population subgroup 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 homeowners applying products containing indaziflam on 

home lawns. There is also a potential for post-application exposure of adults and children 

entering lawn and recreation areas, including golf courses, which have been treated with 

indaziflam. Indaziflam post-application inhalation exposures are expected to be negligible due 

to its low vapor pressure, low application rates, and the types of application equipment used (i.e., 

hand-held equipment that is not likely to generate a vapor). Therefore, a quantitative postapplication inhalation exposure assessment was not considered necessary. 

EPA assessed the following residential exposure scenarios: 

• short -term dermal and inhalation exposures of residential handlers using various types of 

application equipment and formulation types on the proposed residential use sites; 

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

areas; and 

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• short-term postapplication incidental oral exposures of children 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 defined 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 exposure is 100 times lower than the 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 greater 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 short-term post-application dermal exposures 

of adults entering treated lawn areas range from 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 incidental oral exposures) 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 handler and postapplication exposures are possible 

based on the use pattern. However, since the same endpoint and dose were selected for both 

short- and intermediate-term risk assessment, intermediate-term exposures were not assessed. 

Short-term exposure and risk estimates are protective of corresponding 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 handlers range from 100 to 840,000. Since all MOEs 

are greater than or equal to 100, short -term risks for handlers are not of concern. 

2. Occupational Postapplication Exposure and Risk: 

Occupational post-application dermal MOEs ranged from 1,400 to 45,000 and, therefore, are not 

of concern. Post-application inhalation exposures to indaziflam are expected to be negligible due 

to indaziflam’s low vapor pressure and low application rates; in addition, with the exception of 

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forestry 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 Fate 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 persistent in aerobic soil (half-lives > 150 days), persistent in anaerobic 

soil (stable), and persistent in aerobic (half-lives > 200 days) and anaerobic (stable) aquatic 

environments. Indaziflam is subject to aqueous photolysis in clear shallow waters (half-life < 5 

days). Indaziflam is not volatile and therefore, is not likely to be transported via atmospheric 

processes following application. It is a weak acid and is moderately soluble at environmental pH 

values. Indaziflam dissipates in the environment primarily through biotic degradation and 

leaching. Indaziflam degradates are more mobile than the parent (Koc < 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 (Koc 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; indaziflam-carboxylic acid; indaziflam-hydroxyethyl; indaziflam-olefin; 

fluoroethyldiaminotriazine; and fluoroethyltriazinanedione. The toxicity data show that 

indaziflam-olefin and indaziflam-hydroxyethyl are of similar toxicity to the technical grade 

active ingredient (TGAI), based on the most sensitive taxa tested, while indaziflamhydroxyethyl, FDAT, and triazine indanone demonstrate less toxicity than that of the parent. 

Aquatic exposure estimates are based on a total toxic residue approach of indaziflam + residues 

of concern (two major photodegradates: indaziflam-olefin and indaziflam-hydroxyethyl). 

Terrestrial exposure estimates are based on the residue levels of indaziflam alone. Data are not 

generally available for screening level assessments to assess the terrestrial exposure and effects 

of degradates, as is the case for the assessment 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 parent). 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 conducted on indaziflam’s formulated products. 

Bioaccumulation is not expected for indaziflam. 

To address concerns with the potential leaching 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 leaching to groundwater. Required label language is 

described more fully under “Regulatory Decision”, below. 

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B. Ecological Risk 

Ecological risk characterization integrates the results of the exposure 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 quotient method. For this method, risk quotients 

(RQs) are calculated by dividing exposure estimates 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 indicate potential risk to nontarget 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 laboratory studies that assess 

acute effects are: (1) LC50 (Lethal Concentration at which 50% of treated organisms die, fish and 

birds); (2) LD50 (Lethal Dose at which 50% of treated organisms die, birds and mammals); (3) 

EC50 (Environmental Concentration at which 50% of treated organisms die, aquatic plants and 

aquatic invertebrates) and; (4) EC25 (Environmental Concentration at which 25% of treated 

organisms die, terrestrial plants). The endpoints derived from the results of long-term laboratory 

studies that assess chronic effects are the NOAEL and Lowest Observed Adverse Effect 

Concentration (LOAEL) for birds and mammals and No Observed Adverse Effect Concentration 

(NOAEC) and the Lowest Observed Adverse Effect Concentration (LOAEC) for fish and aquatic 

invertebrates. Risk presumptions 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 Species EEC/EC50 or NOAEC ≥1 

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Aquatic Plants 

 Acute High Risk EEC/EC50 ≥1 

 Acute Endangered Species 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 maximum number of applications, and the shortest 

treatment interval between applications. 

1. Aquatic Organisms

Indaziflam is highly toxic (EC50 = 0.1 – 1 mg a.i./L) to freshwater and estuarine/marine fish, 

moderately toxic (EC50 = 1 -10 mg a.i./L) to highly toxic (EC50 = 0.1 – 1 mg a.i./L) to estuarine 

invertebrates, and slightly toxic (EC50 = 10 - 100 mg a.i./L) to moderately toxic (EC50 = 1 -10 mg 

a.i./L) to freshwater invertebrates on an acute exposure basis. However, due to the nature of the 

uses and indaziflam’s susceptibility to aqueous photolysis, exposure to freshwater and 

estuarine/marine fish and invertebrates is expected to be limited. All RQs for freshwater fish, 

aquatic-phase amphibians, and freshwater invertebrates 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 marine fish and invertebrates are below the LOC 

for acute risk to listed and non-listed species. 

Chronic data is unavailable to assess chronic effects on esturine/maine 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 total ai/L and RQs < 0.01. Based on 

this extrapolation, chronic risk to estuarine/marine fish is not expected. Indaziflam’s limited 

solubility under realistic conditions 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 are 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 more fully under “Regulatory Decision”, below. 

2. Terrestrial Organisms

Indaziflam is practically nontoxic (LD50/LC50 > 2,000 mg a.i./L) to birds on both an acute oral 

and subacute dietary exposure basis. 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 not be determined based on the available data. 

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For chronic studies, treatment-related effects on adult 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 the reproductive effects in the mallard duck is required as a 

condition of registration. Indaziflam is practically non-toxic (LD50 > 2,000 mg a.i./L) to 

mammals on an acute and chronic exposure basis. Indaziflam is practically nontoxic to honey 

bees. Affects to body weight were observed 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 potential 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 Endangered Species Act (discussed further in the 

document under Endangered Species Act). To address and mitigate risks to non-target terrestrial 

plants, label language will be required and is described more fully under “Regulatory Decision”, 

below. 

IV. Regulatory Decision 

The Agency is conditionally registering a technical product, a manufacturing 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 lawns), field grown ornamentals and Christmas trees, commercial 

nursery and landscape plantings, and forestry uses. 

As required by FIFRA, the Agency published a notice of receipt (NOR) of applications in the 

Federal Register (January 27, 2010) to register pesticide products 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 Residential and Commercial Areas, (Lawns, 

Ornamentals, and Hardscapes) Turf, Nurseries, and Forestry”, the associated risk assessments, 

and the proposed labels in docket ID number 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 screening level assessment. However, because of 

uncertainty regarding chronic risk to birds and estuarine and marine invertebrates, the Agency 

has determined additional data requirements are required to better characterize risk. These 

studies are required as a condition of the registration of indaziflam: 

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1. 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 determination 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, chronic 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 treatment 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 applicator responsibilities and requires specific 

techniques to reduce the possibility of spray drift. In addition, surface water advisories, intended 

to reduce run-off of the pesticide into aquatic 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 indaziflam 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 water if used in areas where soils are permeable, 

particularly where the water 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 shallow ground water. This product 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 intertidal 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 for use to avoid spray drift and runoff. A level 

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well maintained vegetative buffer strip between areas to which this product 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 product 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 invertebrates, 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 National Pollutant Discharge Elimination System 

(NPDES) permit and the permitting authority has been notified in writing prior to discharge. Do 

not discharge effluent containing this product into sewer systems without previously notifying 

the local sewage treatment plant authority. For guidance contact your State Water Board or 

Regional Office of the EPA.” 

The Environmental Hazards section has been revised to be consistent 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 formulation products :EPA Reg. 432-1499 

 BCS-AA10717 20 WSP Herbicide (20% indaziflam)

“For use on sod farms, golf courses, and non-crop areas (excluding lawns), do not apply within 

25 feet of ponds, lakes, rivers, streams, ditches, 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 containing aquatic and semi-aquatic plants” 

The proposed decision document specified buffers of 25 feet for “turf” and 50 feet for “all other 

uses.” The new language further clarifies the areas that EPA considers to have the most risk of 

run-off into sensitive 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 more stringent regulations, they must be observed. Avoiding spray 

drift is the responsibility of the applicator or grower. To reduce the potential for drift, the 

application equipment must be set to apply medium 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, narrower spray angles produce larger droplets. Follow 

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the nozzle manufacturer’s directions on pressure, orientation, spray 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 during 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., increasing temperature with increasing altitude) greatly 

increases the potential for drift. Avoid application when conditions 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, including agricultural crop 

areas” in the definition of “sensitive areas.” EPA has concluded 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 requirement to make applications when “wind is 

blowing away from sensitive areas.” This requirement would unintentially eliminate uses where 

sensitive areas are adjacent on all sides of the application site. EPA has determined that a winddirection restriction is unnecessary, since the required buffers are adequate mitigation to 

prevent spray drift onto sensitive areas. 

“Spray Drift Management (Golf Courses; 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. For use on golf courses and commercial lawns, the 

boom height must be no higher than 3 feet above the ground and nozzle tips must be set to spray 

out medium to very coarse spray droplets. Applications to residential lawns must be made by 

equipment that maintains coarse spray droplets (to reduce drift).” 

EPA has increased the maximum boom height from 2 to 3 feet to correspond with realistic 

application equipment limitations. 

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“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 trees are tolerant to indaziflam herbicide.” 

“Spray Drift Management (Conifers/Christmas Trees): 

Conifers including Christmas trees are tolerant to foliar applications of indaziflam. In Christmas 

tree farm operations, direct the spray to the base of the trees on a band or broadcast application.” 

C. Public Interest 

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

“Review of Public Interest Finding 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 controlling annual blue grass in turf compared to prodiamine and 

pendimethalin. Indaziflam has a unique mode of action which is not found 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 public’s interest. Therefore, the Agency grants 

these conditional registrations. 

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