Proposed Registration of Fenazaquin on 

Ornamentals, Christmas Tree Plantations, 

Non-Bearing Tree Fruits and Nuts, and 

Established Ornamental Landscape Plantings 

for the Control of Mites and Insects 

February 18, 2010 

U.S. Environmental Protection Agency 

Office of Pesticide Programs 

Registration Division 
2/18/2010 

Proposed Registration of Fenazaquin on Ornamentals, Christmas Tree 

Plantations, Non-Bearing Tree Fruits and Nuts, and Established Ornamental 

Landscape Plantings for the Control of Mites and Insects 

Regulatory Rationale 

The Agency is proposing to grant the first registrations of the active ingredient, fenazaquin, 

formulated as a technical and an end-use product, for application to greenhouse and shadehouse 

ornamentals, established ornamental landscape plantings, Christmas tree plantations, and nonbearing fruit and nut trees to control mites and insects. Previously, the Agency had established 

import tolerances for fenazaquin for apples, pears, and citrus fruits.

1. Human Health Risk 

Following repeated oral doses rats, hamsters and dogs exhibited non-specific effects 

characterized by decrease in body weight, body weight gain, food intake, and food efficiency. 

These effects occurred at the highest tested doses and did not progress in severity with time. 

There was no evidence of developmental or reproductive toxicity, mutagenicity or 

carcinogenicity. Although neurotoxicity, immunotoxicity, and dermal toxicity studies are needed 

to complete the database, there are no concerns for neurotoxicity or immunotoxicity based on the 

results of the existing studies and a Point of Departure to assess risk from dermal exposure was 

extrapolated from an acceptable oral study. 

a. Toxicological End Points 

1. Acute: EPA established an acute reference dose (aRfD) and an Acute Population Adjusted 

Dose (aPAD) of 0.1 mg/kg/day for the general population including infants and children and 

females 13+ years of age, based on a rat developmental toxicity study. The maternal LOAEL = 

40 mg/kg/day, based on findings (as early as GD 6-9) of decreased body weight gain, food 

intake, and food efficiency supported by clinical signs of acute toxicity in the acute oral study. 

There was no evidence of a single dose effect on the developing fetus. 

2. Chronic Dietary: EPA established a chronic reference dose (cRfD) and a Chronic Population 

Adjusted Dose (cPAD) of 0.05 mg/kg/day for all populations, based on a rat two-generation 

toxicity study. The LOAEL = 25 mg/kg/day based on excessive salivation and decreased body 

weight/weight gain and food intake. 

3. Short-Term Dermal and Inhalation: EPA established a Level of Concern (LOC) for the 

Margin of Exposure (MOE) of 100, based on a rat developmental toxicity study. The maternal 

LOAEL = 40 mg/kg/day, based on decreased body weight gain, food intake, and food efficiency. 

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4. Intermediate-Term Dermal and Inhalation: EPA established a Level of Concern (LOC) for the 

Margin of Exposure (MOE) of 100, based on a 90 Day Feeding Study (Dogs). The LOAEL = 15 

mg/kg/day, based on decreased body weight gain, body weight gains, food consumption, and 

food efficiency. 

5. Cancer: EPA has classified fenazaquin as “Not likely to be Carcinogenic to Humans” based 

on the absence of significant tumor increases in two adequate rodent carcinogenicity studies. 

b. Occupational Risk 

Short-term occupational handler exposure is possible via the dermal and inhalation routes, and 

short-/intermediate-term postapplication exposure may occur via the dermal route based on the 

proposed use pattern. 

Handler Exposure and Risk: For all exposure scenarios (except “Mixing/Loading Liquid and 

Applying with High-Pressure Handwand”), the MOEs range from 320 to 4800 and thus provide 

a margin of protection greater than the Agency’s level of concern (LOC=100), provided handlers 

wear personal protective equipment (PPE, i.e. "baseline" clothing, which includes: long sleeve 

shirt, long pants, shoes and socks) and gloves. For the one exception, the addition of coveralls 

provides greater protection such that the estimated MOE of 89 increases to 140. The estimated 

MOE of 89 is based on the conservative assumption of 100% dermal absorption and an 

extrapolated PoD from an oral dose study. Data from a 28-day route-specific dermal toxicity 

study would provide additional certainty in the estimated risk from dermal exposures. The label 

will reflect the additional PPE for this scenario. 

Occupational Postapplication Exposure and Risk: Occupational postapplication exposure is 

possible for workers entering treated areas to tend ornamentals in nurseries, greenhouses, and 

landscapes. Short- /intermediate-term postapplication exposure may occur via the dermal route 

based on the proposed use pattern. The activities evaluated include hand pruning, harvesting, and 

burlapping containerized ornamentals. The short- and intermediate-term dermal MOEs for 

occupational postapplication are greater than the LOC of 100 on the day of application 

(indicating a Re-Entry Interval of 12 hours, the shortest interval for re-entry of treated areas); and 

therefore, are not of concern. 

c. Residential Risk 

An emulsifiable concentrate liquid (GWN-1708) is proposed for use as a single application per 

cropping season to established ornamental plantings in residential areas and recreational sites 

such as golf courses and parks. When determining the potential for residential exposure, the 

Agency considers foliar residues, leaf to skin residue transfer and exposure time. In the case of 

fenazaquin, exposure potential to adults and children would be negligible for the following 

reasons: 1) Activities such as pruning or thinning ornamentals or playing in and around 

ornamentals when residues may be present on the day of the single application per cropping 

season are unlikely to co-occur; 2) if present, leaf to skin residue transfer would be negligible 

because of the minimal frequency and duration of contact. Based on the frequency of application 

and unlikely postapplication exposure, there are no residential risk concerns for this use pattern. 

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d. Aggregate (Food + Drinking Water) Risk 

Acute: The acute dietary analysis (food and drinking water) made at the 95th percentile indicate 

risk estimates are below the 100% of the aPAD threshold level of concern for each population 

subgroup. For the most highly exposed population subgroup, children 1-2 years of age, acute 

dietary risk was estimated to be 24% of the aPAD with an exposure of 0.023546 mg/kg/day. 

Chronic: The chronic dietary analysis (food and drinking water) yielded risk estimates well 

below 100% of the cPAD threshold level of concern for each population subgroup. For the most 

highly exposed population subgroup, children 1-2 years of age, chronic dietary risk estimate was 

13% of the cPAD with an exposure of 0.006251 mg/kg/day. 

Aggregate: Because residential exposure to fenazaquin from its proposed use on ornamentals 

in residential areas is expected to be negligible, short-, intermediate-, and long-term aggregate 

risk assessments considering background exposure from food and water pathways were not 

conducted. Therefore, the components of aggregate risk are residues in food and drinking 

water only. 

2. Environmental Risk 

a. Environmental Fate and Exposure 

Fenazaquin is moderately persistent in soil with a half-life of approximately 8 weeks. It has a 

very high Koc and thus will adsorb strongly to soils and sediments. Its low vapor pressure and 

Henry’s Law Constant suggest that volatilization from soil and water is not likely. However,

particulates adsorbed to soil could move off-site by soil erosion to adjacent water bodies. 

Fenazaquin has a low solubility in water of approximately 0.1 mg/L. Though fenazaquin has a 

high log Kow , available bioaccumulation data do not demonstrate a potential to bioaccumulate in 

fish. 

Persistence: Fenazaquin persists in abiotic aqueous solutions for at least one month, except at 

pH 5 (half-life 9.6 days). Although fenazaquin has the potential to undergo direct photolysis in 

abiotic aqueous media, direct photolysis is slow (estimated half-life approximately 30 days). 

The half-life of fenazaquin in a single soil incubated under aerobic conditions was estimated to 

be 51 days. 

Transport: Fenazaquin adsorbs strongly to soils as indicated by the Freundlich Kocs ranging 

from 15,800 in sand to 101,083 in clay loam soils. Its low vapor pressure (1.9E-5 Pa at 25°C) 

and Henry’s Law Constant (4.25E-008 Atm-m3

 mole-1) suggest that volatilization of fenazaquin 

from soil and water is not likely a dissipation route. However, particulates adsorbed to soil could 

move off-site by soil erosion to adjacent areas and/or by atmospheric transport of particulates. 

 

Bioaccumulation: Based on the Log Kow of 5.7, fenazaquin has the potential to bioaccumulate in 

aquatic organisms. However, a fish bioaccumulation study indicated BCF factors ranging from 

390x to 1400x with rapid removal of accumulated residues. Thus, bioaccumulation is not 

expected. 

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b. Fish and Aquatic Invertebrate Risk 

Risk Associated with Acute Exposure

1. Freshwater Fish 

Acute toxicity testing indicates that technical fenazaquin is very highly toxic to freshwater fish. 

Available data on the propionic acid metabolite and the 2-(4-tert-buthyl phenyl) ethanol 

degradate indicate that they are less toxic than the parent. Risk quotients based on a screening 

level risk assessment were calculated to be: turf (0.04-0.17); ornamentals/nursery (0.05-0.3); 

residential (0.04); fruit/nut trees (0.04 - 0.28). 

2. Freshwater Invertebrates 

Acute toxicity testing indicates that technical fenazaquin is very highly toxic to freshwater 

invertebrates. Risk quotients based on a screening level risk assessment were calculated to be: 

turf (0.03 -0.12); ornamentals/nursery (0.03-0.21); residential (0.03); fruit/nut trees (0.03-0.19). 

3. Marine/Estuarine Fish 

No ecotoxicity studies on estuarine/marine fish were available. Therefore, a quantitative 

estimation of risk cannot be conducted. Based on risk to freshwater fish, there is potential acute 

risk to estuarine/marine fish. Preliminary findings from an ongoing study with sheepshead 

minnow, which has not yet been reviewed by the Agency, reportedly indicate that 

marine/estuarine fish would not be expected to be more sensitive to fenazaquin than freshwater 

fish. 

 

4. Marine/Estuarine Invertebrates (mollusks) 

A shell deposition study conducted with the eastern oyster indicates that technical fenazaquin is 

very highly toxic to marine/estuarine invertebrates (mollusks). Risk quotients based on a 

screening level risk assessment were calculated to be: turf (0.04-0.17); ornamentals/nursery 

(0.05-0.3); residential (0.04); fruit/nut trees (0.04-0.28). Preliminary findings from an ongoing 

study with mysid shrimp which has not yet been reviewed by the Agency reportedly indicate that 

marine/estuarine invertebrates would not be expected to be more sensitive to fenazaquin than 

freshwater invertebrates. 

 

Risk Associated with Chronic Exposure

1. Freshwater Fish 

A screening level assessment using the chronic endpoint from an early life-stage study with 

technical fenazaquin on rainbow trout and the estimated 60 day average aquatic EEC was 

conducted. No levels of concern for freshwater fish were exceeded. 

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2. Freshwater Invertebrates 

No acceptable chronic studies on freshwater invertebrates are available. Therefore, a 

quantitative estimation of risk cannot be conducted. A non-guideline 28-day study conducted on 

the benthic organism, midge (Chironomus riparius) was reviewed. Using a maximum pore 

water concentration of 0.25 μg/L; the chronic RQ for benthic freshwater invertebrates is 0.09, 

suggesting no chronic risk.

 

3. Estuarine/Marine Fish and Invertebrates 

No chronic toxicity studies on marine/estuarine fish were available to assess the chronic risk to 

estuarine/marine fish and invertebrates. 

Aquatic Risk Characterization 

The aquatic ecotoxicology data base for fenazaquin is limited but additional studies are 

underway. Acute toxicity data show that technical fenazaquin is very highly toxic to freshwater 

fish and aquatic invertebrates. Based on a screening level assessment with conservative 

assumptions, the risk quotients ranged from 0.03 - 0.3. The potential estimated risks are 

considered to be conservative and likely overestimate risk based on these assumptions for the 

following reasons: 

o Conservative assumptions on environmental fate parameters include: Using 

results from one aerobic soil metabolism study, a 51-day half-life was multiplied 

by 3 to estimate the degradation input parameter for exposure modeling (as per 

the Agency’s standard approach for calculating input parameters when data are 

limited). 

o In the absence of aquatic metabolism data, the 153-day half-life in soil was 

multiplied by 2 to estimate the half-life in aquatic systems. 

o Thus, the Estimated Environmental Concentrations (EECs) are considered an 

upper bound estimate and most likely will be lower with additional environmental 

fate data to refine the risk assessment. 

In an aquatic microcosm study, EL-436, an 18% emulsifiable concentrate of fenazaquin, was 

applied through simulated spray drift and runoff to an artificial pond. The test animals were 

bluegill sunfish and daphnia. The peak water concentration of fenazaquin in the microcosm 

study was 0.52 μg a.i./L, and decreased 97% after 14 days. As expected based on the laboratory 

toxicity studies conducted with bluegill sunfish and daphnia, and the exposure profile simulated 

in the microcosm study, there were no observed effects in the microcosm study. In fact, 

concentrations measured in the microcosm study were lower than those for which no effects 

were observed in the laboratory studies. 

In interpreting these results, it is also informative to compare the exposure profile achieved in the 

microcosm study with the expected environmental concentrations predicted by the exposure 

modeling done for the ecological risk assessment. Model-estimated fenazaquin concentrations in 

water used in the risk assessment were 1.16 μg/L (peak), 0.49 μg/L (21-day average), and 0.34 

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μg/L (60-day average); concentrations that are indeed higher than those measured in the artificial 

pond study, both in terms of a peak concentration and also longer term exposures. It is expected 

that, once submitted, the additional environmental fate data will provide confirmatory evidence 

that the aquatic risk assessment is conservative and that exposure concentrations are most likely 

lower than predicted by the aquatic exposure modeling. 

A new aquatic invertebrate life-cycle study (Daphnia magna) is needed to address uncertainties 

regarding risk to freshwater invertebrates. The submitted study with Daphnia magna had 

excessive variation in concentration levels and significant effects detected between the negative 

and solvent control groups, indicating possible adverse effects from the solvent in the study. 

c. Risk to Aquatic Plants 

There are no risk concerns for listed aquatic non-vascular plants. The RQ for non-listed nonvascular plants was not estimated because no effects were observed at the highest concentration 

tested, 208 μg a.i./L. Therefore, the EC50 would be greater than 208 μg/L. This concentration is 

higher than the solubility of fenazaquin in water. There is an uncertainty with the estimated risk 

for non-vascular plants because it is based on the results of one species. Aquatic vascular plants 

were not tested. Therefore, there is an uncertainty associated with aquatic vascular plants as 

well, although limited due to the effect on non-vascular plants (green algae) and the mode of 

action for this pesticide, which is not expected to affect plants. 

 

d. Avian Risk

Acute Risk

No acute risk to birds is predicted. 

Chronic Risk

No chronic risk to birds is predicted. 

e. Mammalian Risk 

Acute Risk

The acute RQs varied from 0.20 to < 0.01; therefore acute risk to mammals is predicted. For 

piscivorous (fish-eating) mammals, the acute RQs varied from 0.197 to 0.014, also suggesting 

risk concerns through this route of exposure. 

Chronic Risk

The chronic RQs varied from 1.09 to 0.01. There are no chronic concerns for mammals on a 

dietary basis. On a dose basis, the RQ greater than 1 for small mammals eating short grass 

suggests risk concerns. However, since the RQ is only slightly above the concern level and the 

NOAEL is based on no effects at the highest dose tested, chronic risk to mammals is not 

expected.

For piscivorous (fish-eating) mammals, the chronic RQs varied from 1.06 to 0.077. Chronic risk 

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to piscivorous mammals is not expected, as the NOAEL is based on no effects at the highest dose 

tested and RQs estimated by the KABAM model may be conservative as the model 

underestimated the rate of depuration, by an order of magnitude, as compared with the 

depuration rate determined in the fish accumulation study.

f. Terrestrial Invertebrates

1. Honey Bee 

The 48-hour contact LD50 is 1.21 μg ai/bee with a NOAEC if 0.375 μg ai/bee and a LOAEC of 

0.75 μg/bee based on mortality. Based on this toxicity data, fenazaquin is classified as ‘highly 

toxic’ to honeybees on an acute contact basis. Thus, direct contact with fenazaquin is likely to 

result in adverse effects to beneficial terrestrial insects. This would be expected because 

fenazaquin is a miticide/insecticide. Risk to honeybees and other pollinators is expected to be 

greatest for direct application of this product to blooming crops, weeds, and ornamental plants or 

through spray drift to these areas. There is uncertainty about risk to pollinators from extended 

residual toxicity following application of fenazaquin because a honey bee toxicity of residues on 

foliage study has not been submitted. 

2. Earthworm 

In addition, the LD50 from a 14-day study in the earthworm Lumbricus terrestris, is 1.93 mg 

ai/kg ww soil with a NOAEC of 0.044 mg ai/kg ww soil and a LOAEC of 0.386 based on 

mortality. The estimated concentration of fenazaquin in the top 15-cm of soil, based on the 

application rate of 0.2625 lbs a.i./A, is 0.147 mg a.i./kg soil, is only 9.7 times lower than the 14-

day LD50 value for the earthworm and within the range of the NOAEC and LOAEC. The halflife for fenazaquin in soil is 51 days or longer. Therefore, it is possible that there may be some 

mortality for soil dwelling invertebrates following fenazaquin application. 

g. Plants 

The RQs were all < 0.1 suggesting no risk for any terrestrial monocots or dicots. In addition, 

risk to terrestrial plants is not anticipated due to fenazaquin’s mode of action; disruption of insect 

mitochondria. 

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PROPOSED REGISTRATION DECISION 

The Gowan Company of Yuma, Arizona, submitted applications for these first two registrations 

(Fenazaquin Technical and GWN-1708 Miticide/Insecticide) on April 2, 2007. The requested 

application use is for the control of mites and whiteflies on ornamentals (outdoor and 

greenhouse-grown), Christmas trees (plantations), established ornamental landscapes (including 

interiorscapes and around residential premises), and on non-bearing fruit and nut trees. The 

Agency published a Notice of Receipt for these first registrations on February 4, 2008 and 

received no comments. 

The human health risk assessment concluded that the databases are adequate for dietary and 

occupational assessment for registration of one technical and one end-use fenazaquin 

formulation. Since the application for registration of fenazaquin was received by the Agency, 

EPA has added additional guideline requirements for toxicity testing, for which sufficient time 

has not yet elapsed to generate data. These additional studies are proposed to be required within 

three years as a condition of the registration of fenazaquin: 

• Acute Neurotoxicity Screening Battery (rat) 

• 90 Day Neurotoxicity Screening Battery (rat) 

• Immunotoxicity Study 

In addition, the following studies are proposed to be required to provide additional certainty in 

the estimated risk from dermal and inhalation exposures. 

• 28-Day Dermal Toxicity Study 

• 28-Day Inhalation Toxicity Study 

EPA has considered the entire fenazaquin toxicity data base for potential neurotoxic and 

immunotoxic effects. Although there are uncertainties in the absence of the required acute and 

subchronic neurotoxicity and immunotoxicity studies, EPA does not believe it necessary to 

assign a database uncertainty factor (UFdb)for the lack of these data based on the following: 1) 

the NOAEL used for the acute dietary risk assessment is protective of the clinical signs 

indicative of neurotoxicity in the acute oral study and 2) based on the toxicity profile of this 

chemical, it is unlikely that the results of an immunotoxicity study would result in a NOAEL 

lower than the point of departure used for chronic, dermal and inhalation risk assessments. 

The environmental fate and effects review concluded that the databases are adequate for a 

screening level assessment. However, because of uncertainty regarding risk to aquatic organisms 

and honey bees, EPA has determined additional data requirements are required to better 

characterize risk. These studies are proposed to be required as a condition of the registration of 

fenazaquin: 

• Acute toxicity estuarine/marine fish 

• Acute toxicity estuarine/marine invertebrates (mysid) 

• Aquatic invertebrate life-cycle 

• Avian acute oral toxicity test (passerine species) 

• Avian reproduction study (waterfowl) 

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• Honey bee toxicity of residues on foliage 

• Aerobic soil metabolism 

• Aerobic aquatic metabolism 

Pending submission of this data, EPA will require a 100-foot buffer around water bodies. This 

buffer zone reduces the RQs to below the LOC for all aquatic organisms. 

In order to protect bees, fenazaquin will be labeled with the restriction “Do not apply this 

product or allow it to drift to blooming crops, weeds or ornamentals while bees are visiting the 

treatment area.” Due to possible phytotoxicity, fenazaquin may not be applied to roses which are 

attractive to bees. Fenazaquin is limited to one application per cropping cycle and aerial 

application is prohibited. 

Public Interest

EPA believes that the registration of technical fenazaquin and the end use product, GWN-1708, 

are in the public interest. Fenazaquin is in the quinazoline chemical class, which is a new class 

of pesticide chemistry in the U.S. The target pests, mites and whiteflies, are known for quickly 

developing resistance and controlling them has historically been challenging. According to the 

Agency’s Pesticide Registration Notice 2001-5; Guidance for Pesticide Registrants on Pesticide 

Resistance Management Labeling, “the management of pesticide resistance development is an 

important part of sustainable pest management and this, in conjunction with alternative pest 

management strategies and Integrated Pest Management (IPM) programs, can make significant 

contributions to reducing risks to humans and the environment.” 

The proposed label for GWN-1708 identifies fenazaquin as a “Group 21 Acaricide” with the 

mode of action stated on the label as mitochondrial electron transport inhibition. As defined by 

the Insecticide Resistance Action Committee Mode of Action Classification, pesticides in Group 

21 are “Mitochondrial complex I electron transport inhibitors,” and will affect energy 

metabolism in the target pests. Registration of GWN-1708 will provide growers with an 

additional tool from a new chemical class to use in management of mites and whiteflies. 

Additionally, fenazaquin is considered to be of low toxicity to human health across many 

endpoints. 

For the proposed use sites, fenazaquin may be used instead of some insecticides in the 

neonicotinoid class and the keto-enol class, and miticides such as dicofol, etoxazole, avermectin 

and clofentezine. In these cases, fenazaquin may compare equally or more favorably in human 

toxicity and ecotoxicity risk. 

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Proposed Decision 

The Agency believes, in accordance with FIFRA 3(c)(7)(C), that use of fenazaquin on 

ornamentals, Christmas tree plantations and nonbearing fruit and nut trees while awaiting 

conditional data will not cause any unreasonable adverse effect on the environment and that its 

use is in the public interest. Therefore, the Agency proposes to grant these conditional 

registrations. 

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