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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

OFFICE OF 

CHEMICAL SAFETY AND 

POLLUTION PREVENTION

 

MEMORANDUM

Date: November 8, 2010 

SUBJECT: Tau-Fluvalinate. Human Health Assessment Scoping Document in Support of 

Registration Review. 

PC Code: 109302 DP Barcode: D378275 

Decision No.: 434039 Registration No.: NA 

Petition Nos.: NA Regulatory Action: NA 

Risk Assess Type: Single Chemical Aggregate 

(Registration Review Problem Formulation) 

Case No.: 2295 

TXR No.: NA CAS No.: 102851-06-9 

MRID No.: NA 40 CFR: 180.427 

FROM: Danette Drew, Chemist 

 Ideliz Negrón-Encarnación, Ph.D., Chemist 

 Ana Rivera-Lupiáñez, Chemist 

 William A. Irwin, Ph.D., Toxicologist 

 Risk Assessment Branch V 

 Health Effects Division (7509P) 

 Office of Pesticide Programs 

THRU: Jack Arthur, Branch Chief 

 Risk Assessment Branch V 

 Health Effects Division (7509P) 

 Office of Pesticide Programs 

TO: Molly Clayton, Chemical Review Manager 

 Pesticide Re-evaluation Division (7508P) 

 Office of Pesticide Programs 
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Executive Summary 

Tau-fluvalinate, a type II class pyrethroid, is registered as a post-emergent insecticide/miticide 

for the control of a variety of insects in beehives and various outdoor or greenhouse settings. 

There are five EPA registered products: a technical grade for formulating end-use products, three 

liquid formulations and the impregnated plastic strips used for beehives. Tau-fluvalinate has two 

special local needs (SLN) registrations for California for use on carrots, brassica vegetables, and 

cole crops (non-food uses; crops are grown for seed). There is a tolerance for residues of taufluvalinate on honey (0.02 ppm; 40 CFR 180.427), the only registered food use. 

The last detailed human health risk assessment was completed in 2005 (S. Stanton et al., 

D321911, 9/29/05). The Re-registration Eligibility Decision (RED) was issued in September 

2005. 

The available toxicity data for tau-fluvalinate are adequate to assess the chemical’s hazard 

potential although there are several data gaps. An immunotoxicity study is required as a part of 

new data requirements for conventional pesticide registration (40 CFR Part 158). An acute 

inhalation study is required as well as a 90-day/28-day inhalation study. In addition, a 90-day 

dermal study is now required for non-food use applications. An acute neurotoxicity study is also 

being required. 

The developmental neurotoxicity study (DNT) was previously not requested for tau-fluvalinate. 

However, the Agency has new information regarding the potential for increased susceptibility in 

juveniles from pyrethroid exposures, and therefore, the guideline DNT requirement is maintained 

for all pyrethroids including tau-fluvalinate. Despite the existing DNT requirement, the Agency 

has determined that conducting additional DNT studies on any pyrethroids is not likely to 

contribute new information relevant for risk assessment. EPA believes the existing DNTs on six 

pyrethroids (bifenthrin, cyfluthrin, cyhalothrin, cypermethrin, fenpropathrin and deltamethrin) 

provide sufficient information to determine that the conclusions drawn from the DNTs, as 

combined, are applicable to all pyrethroids. Thus, EPA is hopeful that the registrants with DNT 

requirements will elect to cite the existing database to satisfy the DNT requirement rather than 

devoting new substantial resources associated with performing and evaluating new DNT studies. 

Detailed considerations supporting this conclusion can be found in “Pyrethroids: Evaluation of 

Data from DNTs & Consideration of Comparative Sensitivity” (E. Scollon, 1/20/10, D371723),

available at http://www.epa.gov/oppsrrd1/reevaluation/pyrethroids-pyrethrins.html. In an effort 

to ensure the highest level of protection of infants and children, the Agency is continually 

reviewing scientific data regarding the potentially increased susceptibility of pyrethroid 

pesticides as it becomes available. Therefore, the tau-fluvalinate risk assessment may need to be 

revised to incorporate future findings. 

Subsequent to the last risk assessment, the Agency has identified age-dependent pharmacokinetic 

factors associated with all pyrethroid insecticides that may lead to uncertainty regarding effects 

in children. Therefore, HED is recommending that the toxicological points of departure 

and safety/uncertainty factors used for tau-fluvalinate human health risk assessment be re-
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evaluated during registration review. Once the outstanding data have been received, they 

will be evaluated for acceptability and for suitability for use in the risk assessment.

The most recent acute and chronic dietary exposure assessments were unrefined and used 100% 

crop treated assumptions and tolerance-level residues in honey (the only registered food use is in 

beehives). An FQPA safety factor of 1X was used. Exposure from drinking water was 

incorporated in the acute and chronic risk assessments using surface water estimated drinking 

water concentrations (EDWC). The acute and chronic dietary risk assessments (using DEEM) 

indicated that dietary risk estimates were below HED’s level of concern for the general 

population and all population subgroups. 

An updated dietary exposure assessment is recommended under registration review. If 

there are any changes to the toxicological points of departure or safety factors, or if 

EFED’s (Environmental Fate and Effects Division) new drinking water assessment reflects 

changes in the estimated drinking water concentration, those should be incorporated into 

the new dietary assessment. 

Current uses in residential settings include perimeter treatments, outside surfaces (crack and 

crevice), ant mound treatments (spot application) and use on roses, flowers, houseplants, ground 

covers, vines, ornamentals, shrubs and trees. Although tau-fluvalinate is labeled for use in 

residential areas, neither a residential handler assessment nor a residential post-application 

assessment has been performed to date. The residential uses identified in 2005 were restricted to 

commercial applicators; therefore a residential handler (homeowner) assessment was not needed. 

However, since the 2005 assessment, two new EUPs have been registered for use on outdoor 

residential areas. These new outdoor uses should be assessed for potential residential handler 

exposure. 

A post-application exposure assessment of the current residential uses of tau-fluvalinate is not 

necessary as it is HED’s standard practice not to assess post-application residential exposures 

from treated ornamentals or from perimeter, spot, and crack and crevice treatments to patios and 

other outside surfaces. 

The Agency is in the process of examining its policies and processes regarding inhalation risk 

assessment. The need for a bystander inhalation risk assessment for tau-fluvalinate should be 

examined during registration review. 

Aggregate risk estimates for tau-fluvalinate previously only considered combined food and 

drinking water exposures because at that time no residential uses were expected to contribute to 

homeowner exposures of this chemical. Aggregate acute and chronic dietary (food and water) 

exposures were below HED level of concern. Currently registered outdoor uses should be 

assessed for potential residential handler exposures and an aggregate assessment should be 

performed, if necessary. 

There is potential for short- and intermediate-term occupational exposure to tau-fluvalinate 

during mixing, loading, application, and post-application activities. HED has previously assessed 

the use of tau-fluvalinate on carrots/brassica, outdoor/indoor ornamentals, outdoor perimeter 
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treatments (structures, buildings, etc), greenhouses and ant mounds for occupational inhalation

exposures. Assessments of occupational handler scenarios previously evaluated indicate that 

short- and intermediate-term inhalation risks are not of concern to the Agency. It should be 

noted that the mix/load/application scenario for greenhouses should be assessed with low 

pressure hand wand equipment (assessed previously with high pressure hand wand). 

There is no acceptable inhalation study available for tau-fluvalinate. An acute inhalation study 

and a 90-day/28-day inhalation study are required. Once these data have been received, they 

will be evaluated for acceptability and for suitability for use in the inhalation assessments. 

No occupational or residential dermal exposure or risk estimates were quantitatively assessed as 

part of the 2005 RED. No toxicological dermal endpoints were identified for tau-fluvalinate at 

that time; therefore, a quantitative handler and post-application dermal exposure and risk 

assessment was not performed. The mandatory 90-day dermal study will provide the 

necessary data to quantitatively assess potential occupational and residential handler and 

post-application dermal exposure risk to tau-fluvalinate. 

Tau-fluvalinate is a member of the pyrethroid class of insecticides. This class also includes 

permethrin, cypermethrin, cyfluthrin, tau-fluvalinate, bifenthrin, fenpropathrin, and lambdacyhalothrin, among others. EPA developed a draft science policy document on the proposed 

common mechanism of toxicity for naturally-occurring pyrethrins and synthetic pyrethroids 

(Proposed common mechanism grouping for the pyrethrins and pyrethroids, draft, May 19, 2009; 

http://www.regulations.gov/search/Regs/home.html#documentDetail?R=09000064809a62df ). 

This document was supported by the FIFRA Scientific Advisory Panel (SAP) and is available in 

the docket 

(http://www.regulations.gov/search/Regs/home.html#documentDetail?R=0900006480a1f8d7). 

EPA will finalize the policy document on the pyrethroid common mechanism of toxicity taking 

into account the SAP comments. Pesticides with a common mechanism of toxicity are subject to 

cumulative risk assessment under the FQPA. Research is on-going by EPA’s Office of Research 

and Development (ORD) to make improvements to the Stochastic Human Exposure and Dose 

Simulation (SHEDS) probabilistic exposure model, which are important for the cumulative risk 

assessment. EPA ORD is also developing physiologically-based pharmacokinetic models for 

several pyrethroids. The status of both of these research modeling efforts was reviewed by the 

FIFRA SAP in July, 2010 and meeting materials are available in the docket

(http://www.regulations.gov/search/Regs/home.html#docketDetail?R=EPA-HQ-OPP-2010-

0378). For information regarding EPA’s efforts to evaluate the risk to pyrethroids, see 

http://www.epa.gov/oppsrrd1/reevaluation/pyrethroids-pyrethrins.html.

Hazard Identification/Toxicology 

Tau-fluvalinate, like other pyrethroid insecticides, causes neurotoxicity in insects and mammals 

by the modulation of nerve axon sodium channels. Pyrethroids interfere with the ability of the 

nervous system to relay nerve transmissions resulting in tremors, whole body convulsions, or 

excessive salivation, among other effects. The tau-fluvalinate mammalian studies demonstrate 

typical clinical signs associated with pyrethroid neurotoxicity, including excessive grooming, 

bulging eyes, abnormal stance, ruffled fur, hyperactivity, salivation, ataxia, muscle spasms, 
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tremors, gait abnormalities, startle response hyper reaction and more. Some evidence of nerve 

degeneration was seen at higher doses in the acute neurotoxicity study. 

The available toxicity data for tau-fluvalinate are adequate to assess the chemical’s hazard 

potential although there are several data gaps. An immunotoxicity study is required as a part of 

new data requirements for conventional pesticide registration (40 CFR Part 158). An acute 

inhalation study is required as well as a 90-day/28-day inhalation. In addition, a 90-day dermal 

study is now required for non-food use applications. An acute neurotoxicity study is also being 

required. The developmental neurotoxicity study (DNT) was previously not requested. However, 

the Agency has new information regarding the potential for increased susceptibility in juveniles, 

and therefore, the DNT is currently required for all pyrethroids. 

Tau-fluvalinate is moderately acutely toxic, having been classified in Toxicity Category II by the 

oral route of exposure and Category III by the dermal route. It is not a primary irritant to either 

the eye (Toxicity Category III) or skin (Toxicity Category IV) and is not a dermal sensitization 

agent. The principle systemic effects observed in sub-chronic and chronic studies include 

reductions in body weight/body weight gain (dogs and rats), liver weight changes (dogs and rats) 

and chronic nephritis (mouse). 

No evidence of carcinogenicity was demonstrated in mice or rats, and there is no concern for 

mutagenicity. Tau-fluvalinate was negative for mutagenic effects in a battery of tests, including 

reverse mutation in Salmonella typhimurium, sister chromatid exchange in CHO cells, mouse 

lymphoma mutagenic assay, mammalian cells in culture transformation assay and unscheduled 

DNA synthesis in rat hepatocytes. 

The rat developmental toxicity study did not demonstrate developmental toxicity at the highest 

dose tested. The rabbit developmental toxicity demonstrated some signs of skeletal variations 

(curved tibia and fibula) but at the same dose where maternal toxicity was seen. There were no 

effects of tau-fluvalinate on reproductive performance. The offspring were noted to have tremors 

in one generation and to have slight body weight decrease in another generation, but these effects 

occurred at a dose that was also toxic to the parents. There is no quantitative or qualitative 

evidence of increased susceptibility of rat or rabbit fetuses after in utero and/or postnatal 

exposure to tau-fluvalinate in the developmental and reproduction studies. Dose-response 

relationships are well-characterized and NOAELs/LOAELs have been identified for the 

critical effects. Despite the lack of quantitative and qualitative susceptibility found in the 

guideline studies, new information (see web link below) gives the Agency cause for residual 

uncertainty for potential sensitivity. The science supporting this conclusion can be found in 

“Pyrethroids: Evaluation of Data from DNTs & Consideration of Comparative Sensitivity” (E. 

Scollon, 1/20/10, D371723), available at http://www.epa.gov/oppsrrd1/reevaluation/pyrethroidspyrethrins.html. In an effort to ensure the highest level of protection of infants and children, the 

Agency is continually reviewing scientific data regarding the potentially increased susceptibility 

of pyrethroid pesticides as it becomes available. Therefore, the tau-fluvalinate risk assessment 

may need to be revised to incorporate future findings. 
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Previously, the special FQPA safety factor was reduced to 1X, since there were no residual 

uncertainties for pre- and/or postnatal toxicity. However, during registration review, EPA will reevaluate all toxicological endpoints and safety factors taking into consideration all available data. 

Based on a weight-of-evidence approach, a conservative NOAEL for neurotoxic effects has been 

identified for tau-fluvalinate. This approach is based on the results of 2 studies: the rat chronic 

feeding study and the rat subchronic neurotoxicity study. In the chronic study in the rat, clinical 

signs of neurotoxicity including: excessive salivation, pawing at bottom of the cage, lacrimation, 

abnormal stance, ruffling, and transient hyperactivity followed by hypoactivity were observed at 

1.0 mg/kg/day; these effects were not seen at 0.5 mg/kg/day. These signs were observed during 

the first 3 hours after dosing and subsided within 6 hours. In the subchronic study in the rat, 

excessive grooming and bulging eyes were noted in the animals at 2 mg/kg/day (the lowest dose 

tested).These two studies were evaluated in parallel because the clinical signs of neurotoxicity in 

the rat chronic study are transient and mentioned in the report but not well documented. 

However, HED believes that these early onset neurotoxic effects are consistent with the typical 

clinical signs associated with pyrethroids and are most likely the result of preliminary nerve 

stimulation and/or agitation. At the next highest dose tested in the chronic rat study (2.5 

mg/kg/day), the development of tropic (plantar) ulcers could possibly be indicative of amplified 

and prolonged nervous system stimulation/agitation. Furthermore, the results of the 90-day 

subchronic neurotoxicity study are consistent with the results of the rat chronic feeding study, 

demonstrating marked evidence of neurotoxicity at a similar low dose. HED believes that the 

results of these 2 studies taken together form the basis for a clear NOAEL of 0.5 mg/kg/day for 

neurotoxic effects, with minimal effects beginning to be seen at 1.0 mg/kg/day in the chronic 

study, thus establishing a conservative LOAEL. The selection of this LOAEL is further 

supported by the increasingly severe neurotoxic effects seen at the higher doses of 2 mg/kg/day 

and 2.5 mg/kg/day, respectively, in the shorter- term subchronic study and longer-term chronic 

feeding study. HED believes that this conservative determination is protective for all population 

subgroups. This NOAEL was applied to acute and chronic dietary exposures and short-term and 

intermediate- term inhalation exposures (see Appendix B for 2005 toxicological dose and 

endpoint selections). 

No toxicity endpoint was selected for dermal exposure to products containing tau-fluvalinate. 

Dermal exposure to products containing tau-fluvalinate was previously expected to be largely 

self-limiting due to the irritation that occurs as a result of the “pyrethroid reaction” (skin 

abrasions due to scratching). A 90-day dermal toxicity study is now being required.

Residue Chemistry 

The name “fluvalinate” is currently the common name for the racemic mixture of the 4 isomers 

of cyano-(3-phenoxyphenyl)methyl N-[2-chloro-4-(trifluoromethyl)phenyl]-valinate; 

“tau-fluvalinate” is the term used for the half resolved mixture (2 of the 4 isomers). In the 

residue chemistry chapter of the 2005 RED, the tau-fluvalinate name was used when it could be 

determined that the data were actually for the half resolved mixture; otherwise, the name 

fluvalinate was used (D300204, J.J. Morales, 2/22/05). The nomenclature, registration numbers, 

PC Code, chemical structure and physiochemical properties of tau-fluvalinate are listed in 

Appendix C. 
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The nature of the residue for use of tau-fluvalinate in beehives is understood (D300204, J.J. 

Morales, 2/22/05). The registered use does not involve the direct application of tau-fluvalinate to 

honey, but involves the possible transfer of secondary residues from tracking by the bee colony 

as they make contact with the insecticide strips. Therefore, HED determined that only the parent 

compound, tau-fluvalinate, is the residue of concern. A tolerance of 0.02 ppm was established 

for residues of tau-fluvalinate in honey. In addition, the product label restricted the use of 

beeswax (for human consumption) from bee combs treated with tau-fluvalinate (EPA Reg. No. 

2724-406). Currently, there are no registered uses of tau-fluvalinate on plant commodities (use 

on carrots, brassica vegetables, and cole crops grown for seed are non-food uses), neither in 

feedstuff commodities nor for direct animal treatments. However, acceptable metabolism studies 

of tau-fluvalinate in alfalfa, apple, ruminant and poultry are available and the residue of concern 

was established as tau-fluvalinate. 

Acceptable enforcement methods for tau-fluvalinate in honey are available. In addition, the 

FDA multi-residue methods published in the PAM Volume I, section 302 and 303, showed an 

acceptable recovery (>80%) for tau-fluvalinate. 

In the product chemistry chapter of the 2005 RED one deficiency was identified in the taufluvalinate database (D311824, J.J. Morales, 2/22/05), the UV/vis absorption spectra of the 

Wellmark 87.2% test grade active ingredient of tau-fluvalinate (Reg. No. 2724-481) was not 

available. These studies were submitted by the registrant and evaluated by OPP Technical 

Review Branch. The studies were found to be acceptable according to OPPTS 830.7050 

guidelines (D321133, S.B. Mathur, 9/7/05). 

Dietary Exposure 

Unrefined acute and chronic dietary exposure assessments were previously conducted with 

DEEM-FCIDTM and Lifeline TM software. The risk calculations performed with both software 

were based on consumption data from the USDA’s Continuing Surveys of Food Intakes by 

Individuals (years 1994-1996 and 1998), 100% crop treated assumptions and tolerance-level 

residues of 0.02 ppm in honey (D300203, S. Stanton, 3/11/05). In addition, an FQPA safety 

factor of 1X was used. Exposure from drinking water was incorporated in the acute and chronic 

risk assessments using the 1 in 10 year’s annual peak and average concentrations of surface 

water, respectively. Nearly all the estimated dietary exposure to tau-fluvalinate was from 

drinking water. 

The acute and chronic dietary risk assessments indicated that for all uses the risk estimates were 

below HED’s level of concern (<100% aPAD and < 100% cPAD) for the general population and 

all population subgroups. For the acute dietary risk assessment, the highest exposed population 

subgroup at the 95th exposure percentile was infants (<1 year old) accounting for 5.1% of the 

aPAD with DEEM-FCID TM and 3.9% of the aPAD with Lifeline TM. The chronic dietary risk 

assessment performed with both software also indicated that the highest exposed population 

subgroup were infants at <1% of the cPAD. 
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The last Drinking Water Assessment (DWA) of tau-fluvalinate was performed for the 2005 RED 

(D304067, M. Corbin, 2/3/05). A Tier II approach was used to estimate the surface water 

concentration. The average and peak estimated drinking water concentration of tau-fluvalinate 

in surface water was used for the chronic and acute dietary risk assessments, 0.065 ppb and 1.31 

ppb, respectively. 

A new drinking water assessment will be completed by EFED and will take into account any 

new data submitted to the EPA or published in the literature. Input parameters will also be 

updated to reflect current input parameter guidance. It is anticipated that tau-fluvalinate 

estimated drinking water concentrations (EDWCs) in surface water resulting from registered 

uses will be calculated using PRZM and EXAMS models along with adjustments for percent 

cropped area (PCA). The SCI-GROW model will be used to determine ground water 

concentration resulting from use of tau-fluvalinate. This water assessment will include any 

monitoring data that may be available. 

An updated dietary exposure assessment is recommended under registration review, to include 

any relevant changes to the toxicological points of departure and safety factors. If the new DWA 

reflect changes in the estimated drinking water concentration, those should also be incorporated 

into the new dietary assessment. 

Residential Exposure 

Current uses in residential settings include perimeter treatments, outside surfaces (crack and 

crevice), ant mound treatments (spot application) and use on roses, flowers, houseplants, ground 

covers, vines, ornamentals, shrubs and trees. Although tau-fluvalinate is labeled for use in 

residential areas, neither a residential handler assessment nor a residential post-application 

assessment has been performed to date. The residential uses identified in 2005 were restricted to 

commercial applicators; therefore a residential handler (homeowner) assessment was not needed. 

However, since the 2005 assessment, two new EUPs have been registered for use on outdoor 

residential areas (roses, flowers, houseplants, ground covers, vines, ornamentals, shrubs and 

trees) which do not restrict the use to commercial applicators:1) Reg no. 72155-71 is a 3 in 1 

combination product containing 0.014% tau-fluvalinate (along with imidacloprid and 

tebuconazole). It is a ready- to- use (RTU) spray product. 2) Reg no. 72155-73 is a 3 in 1 

combination product containing 0.61% tau-fluvalinate (along with imidacloprid and 

tebuconazole). The label has instructions for mixing and applying with a pump sprayer or hose 

end sprayer and a second part for use as a ready to spray RTU. These uses should be assessed 

for potential residential handler exposure. 

No dermal exposure or risk estimates were quantitatively assessed as part of the 2005 RED since 

no toxicological dermal endpoints were identified for tau-fluvalinate at that time. The mandatory 

90-day dermal study will provide the necessary data to quantitatively assess potential residential 

handler dermal exposure risk to tau-fluvalinate. 

A post-application exposure assessment of the current residential uses of tau-fluvalinate is not 

necessary as it is HED’s standard practice not to assess post-application residential exposures 

from treated ornamentals or from perimeter, spot, and crack and crevice treatments to patios and 
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other outside surfaces. Additionally, the 2005 risk assessment concluded that the use of the taufluvalinate formulation as spot and perimeter treatment around structures and buildings were not 

wide area broadcast applications and would not likely result in significant post-application 

exposure of adults or children (Tau-fluvalinate - RARC1 (2/9/05), therefore a post-application 

assessment was not performed for these uses and is not currently needed. 

Volatilization of pesticides may be a potential source of post-application inhalation exposure to 

individuals (bystanders) nearby to pesticide applications. The Agency sought expert advice and 

input on issues related to volatilization of pesticides from its Federal Insecticide, Fungicide, and 

Rodenticide Act Scientific Advisory Panel (SAP) in December 2009. The Agency received the 

SAP’s final report on March 2, 2010 

(http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The Agency is in the 

process of evaluating the SAP report and may, as appropriate, develop policies and procedures to 

identify the need for and, subsequently, the way to incorporate post-application inhalation 

exposure into the Agency's risk assessments. If new policies or procedures are put into place, the 

Agency may revisit the need for a quantitative post-application inhalation exposure assessment 

for tau-fluvalinate. 

Aggregate Exposure and Risk Assessment 

In accordance with FQPA, HED considers and aggregates pesticide exposures and risks from 

three major sources: food, drinking water, and residential exposures. In an aggregate 

assessment, exposures from dietary and residential sources are added together and compared to 

quantitative estimates of hazard (e.g., a NOAEL), or the risks themselves can be aggregated. 

When aggregating exposures and risks form various sources, HED considers both the route and 

duration of exposure. 

In the case of tau-fluvalinate, the 2005 aggregate risk estimates only considered combined food 

and drinking water exposures because at that time no residential uses were expected to contribute 

to homeowner exposures of this chemical (D321911, S. Stanton et al, 9/29/05 ). Acute and 

chronic dietary (food and water) exposures were below HED level of concern (<100% aPAD and 

<100% cPAD) for the general population and all population subgroups. 

Current residential uses include perimeter treatments/outside surfaces, ant mound treatments 

(spot application) and ready-to-use sprays for pest control on roses, flowers, houseplants, ground 

covers, ornamentals, shrubs and trees, including a ready-to-use spray formulation that is not 

restricted to commercial applicators. These uses should be assessed for potential residential 

handler exposure and an aggregate assessment should be performed, if necessary. A postapplication exposure assessment of the current residential uses of tau-fluvalinate is not necessary 

as it is HED’s standard practice not to assess post-application residential exposures from treated 

ornamentals or from perimeter, spot, and crack and crevice treatments to patios and other outside 

surfaces. 
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Occupational Exposure 

Use Patterns 

Tau-fluvalinate formulations currently include flowable concentrate, liquid, ready- to- use, and 

impregnated materials. This chemical may be applied as an outdoor general surface spray, 

perimeter treatment, crack and crevice treatment, and mound treatment around commercial and 

domestic dwellings. For treatment of landscape ornamentals and nursery uses, tau-fluvalinate 

may be applied using a broadcast spray, foliar spray, dip treatment, containerized treatment, and 

basal spray treatment. Greenhouse applications include broadcast, fogger, and bench treatments. 

For agricultural uses on carrots, and on brassica and cole crops (CA SLNs), tau-fluvalinate may 

be applied using aerial or ground equipment. Tau-fluvalinate is also labeled for use in the brood 

chambers of bee hives. Treatments to bee hives are made using impregnated strips. The restricted 

entry interval (REI) for all crops is 12 hours. 

The residential uses include perimeter treatments/outside surfaces, ant mound treatments (spot 

application) and ready-to-use sprays for pest control on roses, flowers, houseplants, ground 

covers, ornamentals, shrubs and trees. 

There are five EPA registered products: a technical grade for formulating end-use products, one 

flowable formulation for commercial use only, two ready- to- use pump and hose-end sprays coformulated products (Imidacloprid + Tau-fluvalinate + Tebuconazole) for residential use only, 

and the impregnated plastic strips used for beehives. Appendix D lists the currently registered 

tau-fluvalinate formulated products. 

Maximum rates of application for occupational tau-fluvalinate use vary from 0.15 lb ai/A for 

application by aircraft and ground equipment for carrots, brassica and cole crops grown for seed, 

0.011lb ai/gal for foliar spray applications on field and container-grown ornamentals, 0.0078 

lb/100sq. ft. for broadcast/fog applications of commercial greenhouses (empty), 0.0783 lb ai/100 

gal for dip treatment of foliage and flower cuttings, and 0.0078 lb/1000 sq. ft. for perimeter 

treatments/outside surfaces and perimeter outdoor crack and crevice treatment of 

household/domestic dwellings, commercial/institutional/industrial premises/equipment, paths 

and patios, and 0.0016 lb/ mound for ant mound spot treatment applications. 

The formulated end use product labels Personal Protective Equipment (PPE) include long 

sleeved shirt, long pants, shoes, socks, and chemical resistant gloves. 

Occupational Handler Risk Assessment 

There is potential for short- and intermediate-term occupational exposure to tau-fluvalinate 

during mixing, loading, application, and post-application activities. HED has previously assessed 

the use of tau-fluvalinate on carrots/brassica, outdoor/indoor ornamentals, outdoor perimeter 

treatments (structures, buildings, etc), greenhouses and ant mounds for occupational inhalation

exposures (D319595, Travaglini, R., 07/25/2005). Assessments of occupational handler 

scenarios previously evaluated indicate that short- and intermediate-term inhalation risks are not 
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of concern to the Agency (i.e., and MOE ≥ 100; MOEs range from 180 to 95,000) at either 

baseline or minimum level of personal protection. It should be noted that the 

mix/load/application scenario for greenhouses should be assessed with low pressure hand wand 

equipment based on current HED practices (ExpoSac recommendation, 2010). The scenario was 

assessed previously with high pressure hand wand. A new inhalation exposure assessment with 

the low pressure hand wand should result in higher MOE’s. 

In the case of tau-fluvalinate, there is no acceptable inhalation study available. Inhalation 

exposures were assessed using oral toxicity endpoints (100% inhalation absorption assumed). An 

acute inhalation study was not previously required for tau- fluvalinate (2005 RED); however, 

according to the new Part 158 section 870 rules an acute inhalation study is now mandatory. A 

90-day/28-day inhalation study is also required due to exposure scenarios. The 90-day/28-day 

inhalation study (870.3465) was previously categorized as ‘reserved’ in the 2005 RED. Since only 

short- and intermediate-term exposure to workers is expected based on tau-fluvalinate use pattern, 

a 28-day repeated exposure study (instead of 90-day) will characterize hazard and provide data for 

a more refined inhalation risk assessment. Once these data have been received, they will be 

evaluated for acceptability and for suitability for use in the inhalation assessments. 

Occupational exposure assessments of the tau-fluvalinate impregnated strips for beehives, cut 

flower dipping treatments, and greenhouse foggers have not been previously performed. 

Occupational exposure resulting from use of the beehive strips is expected to be negligible, as 

the only potential times for worker contact are during application, when the beehive keeper 

removes the strips from the containers and places them in the hives, and during removal and 

disposal of the strips. Since beehives are located outdoors, and the vapor pressure of taufluvalinate is low (10 -7 torr) there is negligible potential for inhalation exposure. In order to 

mitigate any potential for dermal exposure, the label requires the use of protective gloves by 

applicators. Therefore, risk assessments for occupational exposure are not required for the 

beehive use. 

For the cut flowers dipping treatments, the Agency believes that the previously assessed high 

pressure hand wand greenhouse scenario (the low pressure hand wand scenario was not assessed) 

would be a comparable, protective estimate of exposure to tau-fluvalinate from dipping 

treatments. 

In the case of greenhouse fog treatments, occupational risks exposures were not previously 

assessed due to lack of inhalation exposure data for this use. However, a tau-fluvalinate 

greenhouse fogger study (MRID 47338007) has been submitted since the 2005 RED and 

inhalation exposure estimates should be assessed for greenhouse fog treatments. 

Post –Application Risk Assessment 

Inhalation 

Occupational post-application exposure to tau-fluvalinate is anticipated to occur based on the use 

pattern of tau-fluvalinate. With the exception of the greenhouse uses, post-application inhalation 

exposure to tau-fluvalinate is expected to be minimal. Based on the Agency's practices, a 

quantitative occupational post-application inhalation exposure assessment was not performed for 

tau-fluvalinate. However, there are multiple potential sources of post-application inhalation 
Page 12 of 27 

exposure to individuals performing post-application activities in previously treated fields. These 

potential sources include volatilization of pesticides and re-suspension of dusts and/or 

particulates that contain pesticides. The Agency sought expert advice and input on issues related 

to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act 

Scientific Advisory Panel (SAP) in December 2009. The Agency received the SAP’s final report 

on March 2, 2010 (http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The 

Agency is in the process of evaluating the SAP report as well as available post-application 

inhalation exposure data generated by the Agricultural Re-entry Task Force and may, as 

appropriate, develop policies and procedures, to identify the need for and, subsequently, the way 

to incorporate occupational post-application inhalation exposure into the Agency's risk 

assessments. If new policies or procedures are put into place, the Agency may re-visit the need 

for a quantitative occupational post-application inhalation exposure assessment for taufluvalinate. 

Dermal 

No occupational post-application dermal exposure or risk estimates were quantitatively assessed 

as part of the 2005 RED. No toxicological dermal endpoints were identified for tau-fluvalinate at 

that time; therefore, a quantitative post-application dermal exposure and risk assessment was not 

performed. The mandatory 90-day dermal study will provide the necessary data to quantitatively 

assess potential occupational post-application dermal exposure risk to tau-fluvalinate. The 

dermal study must be requested and occupational post-application dermal exposure risk 

scenarios quantitatively assessed for all tau-fluvalinate uses. 

The toxicity categories of the active ingredient for acute dermal, eye irritation, and skin irritation 

potential are used to determine the interim REI (Restricted-entry Intervals). The tau-fluvalinate 

technical material has been classified in Toxicity Category III for acute dermal and primary eye 

irritation. It is not a dermal irritant (toxicity Category IV). Per the Worker Protection Standard 

(WPS), a 12-hr restricted entry interval (REI) is required for chemicals classified under Toxicity 

Category III or IV. The registered labels indicate an interim REI of 12 hrs, which is in 

compliance with the WPS. 

Public Health and Pesticide Epidemiology Data 

The OPP Incident Data System (IDS) and the Centers for Disease Control and 

Prevention/National Institute for Occupational Safety and Health (CDC/NIOSH) Sentinel Event 

Notification System for Occupational Risk-Pesticides (SENSOR) database were consulted for 

pesticide incident data on the active ingredient tau-fluvalinate. Additionally, the Agency is 

looking to include findings from the Agricultural Health Study (AHS), beginning with the 

problem formulation phase of registration review (K. Middleton, D378502, 8/10/2010). 

For IDS aggregate summaries, from 2000 to May 25, 2010, there are 91case reported for taufluvalinate. Because it falls within the categories reported as counts (which includes minor, 

unknown or no effects), there is no unique report that provides details about the incident and 

single chemical incidents are not distinguished from multiple chemical incidents. For the main 

IDS from 2000 to May 25, 2010, there was one case reported for tau-fluvalinate in the database 
Page 13 of 27 

with moderate severity. In this case, an unknown age female, reported the following health 

effects: face swelling, hives, welts, and sores inside the mouth. 

For NIOSH SENSOR from 1998 to 2007, seven cases were reported that involved the active 

ingredient tau-fluvalinate. Of these cases, four were reviewed because, in these cases, taufluvalinate was used as a single chemical only and had a certainty classification of definite, 

probable, or possible. The health effects reported included: gastrointestinal (75%), respiratory 

(50%), ocular (25%), neurological (25%), and dermal (25%). Symptoms are not mutually 

exclusive; a patient may have many symptoms. These cases were classified as low to moderate 

severity (three low, one moderate). Two cases (one occupational and one non-occupational) 

were the result of drift exposure. One case involved a landscaper experiencing dermal symptoms 

while applying tau-fluvalinate. One case was exposed while spraying greenhouse ornamentals; 

he took off his respirator and the wind blew the product back in to his face. 

Tau-fluvalinate is not included in the AHS, and therefore not considered in this report. 

Conclusions for Public Health and Pesticide Epidemiology Data

Based on the low frequency of incident cases, there does not appear to be a concern at this time 

that would warrant further investigation. The Agency will continue to monitor the incident 

information and if a concern is triggered, additional analysis will be included in the risk 

assessment. 

Tolerance Assessment and International Harmonization 

Where possible, EPA encourages the harmonization of the US Tolerances and Maximum 

Residue Limits (MRLs) in key export markets. A table with the US tolerances, the Canada 

MRLs, Mexico MRLs and Codex MRLs for tau-fluvalinate in registered RACs is provided in 

Appendix E. These tolerances and MRLs are based on the residue analysis of tau-fluvalinate. 

The only US tolerance is established for tau-fluvalinate residues in honey. Currently, Codex, 

Canada and Mexico does not have MRLs established for the use of tau-fluvalinate. If necessary, 

the Agency will work to harmonize tolerances/MRLs, during registration review. 

On 5/27/2009 HED established interim guidance on writing tolerance expressions for 

enforcement purposes. In order to add clarity to the language used to establish the coverage of 

the tolerance expression and measurement of the level of the residue in the RACs the text in the 

40 CFR § 180.427 should read: “(a) General. (1) Tolerances are established for residues of taufluvalinate, including its metabolites and degradates, in or on the commodities in the table below. 

Compliance with the tolerance levels specified below is to be determined by measuring only taufluvalinate [cyano-(3-phenoxyphenyl)methyl N-[2-chloro-4-(trifluoromethyl)phenyl]-Dvalinate].” 

Environmental Justice 
Page 14 of 27 

There do not appear to be any particular socioeconomic subgroups that may experience a higher 

degree of exposure to tau-fluvalinate. Potential areas of environmental justice concerns, to the 

extent possible, will be considered in future human health risk assessments for tau-fluvalinate, in 

accordance with U.S. Executive Order 12898, "Federal Actions to Address Environmental 

Justice in Minority Populations and Low-Income Populations," 

http://www.epa.gov/compliance/resources/policies/ej/exec_order_12898.pdf. The Office of 

Pesticide Programs (OPP) typically considers the highest potential exposures from the legal use 

of a pesticide when conducting human health risk assessments, including, but not limited to, 

people who obtain drinking water from sources near agricultural areas, the variability of diets 

within the U.S., and people who may be exposed when harvesting crops. Should these highest 

exposures indicate potential risks of concern, OPP further refines the risk assessments to ensure 

that the risk estimates are based on the best available information. 

Cumulative Risk Assessment 

Tau-fluvalinate is a member of the pyrethroid class of insecticides. This class also includes 

permethrin, cypermethrin, cyfluthrin, bifenthrin, fenpropathrin, and lambda-cyhalothrin, among 

others. EPA developed a draft science policy document on the proposed common mechanism of 

toxicity for naturally-occurring pyrethrins and synthetic pyrethroids (Proposed common 

mechanism grouping for the pyrethrins and pyrethroids, draft, May 19, 2009; 

http://www.regulations.gov/search/Regs/home.html#documentDetail?R=09000064809a62df ). 

This document was supported by the FIFRA Scientific Advisory Panel (SAP) and is available in 

the docket 

(http://www.regulations.gov/search/Regs/home.html#documentDetail?R=0900006480a1f8d7). 

EPA will finalize the policy document on the pyrethroid common mechanism of toxicity taking 

into account the SAP comments. Pesticides with a common mechanism of toxicity are subject to 

cumulative risk assessment under the FQPA. Research is on-going by EPA’s Office of Research 

and Development (ORD) to make improvements to the Stochastic Human Exposure and Dose 

Simulation (SHEDS) probabilistic exposure model, which are important for the cumulative risk 

assessment. EPA ORD is also developing physiologically-based pharmacokinetic models for 

several pyrethroids. The status of both of these research modeling efforts was reviewed by the 

FIFRA SAP in July, 2010 and meeting materials are available in the docket

(http://www.regulations.gov/search/Regs/home.html#docketDetail?R=EPA-HQ-OPP-2010-

0378). For information regarding EPA’s efforts to evaluate the risk to pyrethroids, see 

http://www.epa.gov/oppsrrd1/reevaluation/pyrethroids-pyrethrins.html.

Endocrine Disruptor Screening Program 

As required under FFDCA section 408(p), EPA has developed the Endocrine Disruptor 

Screening Program (EDSP) to determine whether certain substances (including pesticide active 

and other ingredients) may have an effect in humans or wildlife similar to an effect produced by 

a “naturally occurring estrogen, or other such endocrine effects as the Administrator may 

designate.” The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 
Page 15 of 27 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine related effects caused by the substance, and 

establish a dose-response relationship between the dose and the E, A, or T effect. 

Between October 2009 and February 2010, EPA issued test orders/data call-ins for the first 

group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. 

This list of chemicals was selected based on the potential for human exposure through pathways 

such as food and water, residential activity, and certain post-application agricultural scenarios. 

This list should not be construed as a list of known or likely endocrine disruptors. 

Tau-fluvalinate is not among the group of 58 pesticide active ingredients on the initial list to be 

screened under the EDSP. Under FFDCA sec. 408(p) the Agency must screen all pesticide 

chemicals. Accordingly, EPA anticipates issuing future EDSP test orders/data call-ins for all 

pesticide active ingredients. 

For further information on the status of the EDSP, the policies and procedures, the list of 67 

chemicals, the test guidelines and the Tier 1 screening battery, please visit our website: 

http://www.epa.gov/endo/. 

Human Studies 

Past tau-fluvalinate risk assessments rely in part on data in generic databases from studies in 

which adult human subjects were intentionally exposed to a pesticide to determine their dermal 

and inhalation exposure. Many such studies, involving exposure to many different pesticides, 

comprise generic pesticide exposure databases such as the Outdoor Residential Exposure Task 

Force database and the Pesticide Handler Exposure Database. EPA has reviewed all the studies 

supporting these multi-pesticide generic exposure databases, and has found no clear and 

convincing evidence that the conduct of any of them was either fundamentally unethical or 

significantly deficient relative to the ethical standards prevailing at the time the research was 

conducted. There is no regulatory barrier to continued reliance on these studies, and all 

applicable requirements of EPA’s Rule for the Protection of Human Subjects of Research (40 

CFR Part 26) have been satisfied. 

Data Requirements 

Toxicology

(See Appendix A for data requirement rationales.) 

• Guideline 870.1300 - Acute Inhalation Toxicity 

• Guideline 870.3250 - 90-Day Dermal Toxicity 

• Guideline 870.3465 - 90-Day/28-Day Inhalation Toxicity 

• Guideline 870.6200a- Acute Neurotoxicity Battery 

• Guideline 870.6300 - Developmental Neurotoxicity Study 

• Guideline 870.7800 – Immunotoxicity 
Page 16 of 27 

Residue Chemistry

No data gaps currently identified. 

Occupational and Residential

No data gaps currently identified.
Page 17 of 27 

Appendix A: Rationales for Toxicology Data Requirements 

Guideline Number: 870.1300 

Study Title: Acute Inhalation Toxicity 

Rationale for Requiring the Data 

The Agency needs an acute inhalation study due to 40 CFR 870.1300 requirements and because acute 

inhalation exposure to workers is expected based on tau-fluvalinate's use pattern. The study design 

simulates the route of acute human exposure via inhalation to tau-fluvalinate. In this study, animals are 

exposed (nose/whole body) to aerosol concentrations of the test material for 6 hours in a single day. A 

detailed toxicological examination including the histopathology of the respiratory system is conducted. 

This route-specific study would provide data for assessing potential risks via the inhalation route. 

Practical Utility of the Data 

How will the data be used? 

This study will identify hazard (i.e. provide a dose and endpoint) following acute inhalation exposures. 

The results will be used in risk assessments as appropriate. 

How could the data impact the Agency’s decision-making? 

 

A sub-chronic inhalation study provides critical scientific information needed to characterize potential 

hazard to the human respiratory system from tau-fluvalinate exposure. In the case of tau-fluvalinate, there 

is no acceptable acute inhalation study available. An acute exposure study that follows the Test 

Guidelines (870.1300) will characterize hazard and provide data for a more refined inhalation risk 

assessment. This requirement is pending resolution of inhalation exposure for existing and possible future 

uses. 

Guideline Number: 870.3250 

Study Title: 90-Day Dermal Toxicity 

Rationale for Requiring the Data 

The sub-chronic (90-day) dermal toxicity study is a new data requirement under 40 CFR Part 158 as a 

part of the data requirements for registration of a pesticide for non-food use. 

The dermal toxicity Test Guidelines (OPPTS.870.3250) is intended to evaluate the toxic effects 

associated with continuous or repeated exposures to a test substance for a period of 90-days. 

The Agency needs a 90-day dermal toxicity study for non-food use pesticides because the dermal route 

will be the primary route of exposures for chemicals designated with this use pattern (i.e., non-food). The 

Agency believes that this study is required because the longer term oral studies (i.e., chronic or 

carcinogenicity studies) which are required for food-use pesticides are usually not required for non-food 

use pesticides. A 21/28 day dermal toxicity test is insufficient to identify potential hazards for non-food 

use pesticides because of the concern for the longer duration exposure associated with this use pattern. 

For example, professional applicators may be subjected to repeated exposure during the 3 month period 

of peak summer infestation. For this type of increased exposure, professional applicators may not be 

adequately protected using data from a 21/28-day study. 

Practical Utility of the Data 

How will the data be used? 

A route specific (i.e., dermal) study will provide critical scientific information needed to characterize 

potential hazard to the human population exposed to tau-fluvalinate by the dermal route. This study will 

provide a dose and a toxicological endpoint of concern for quantification of risks for dermal exposures. 
Page 18 of 27 

This study would eliminate the uncertainties associated with the use of an oral study with a default (100% 

oral equivalent) dermal absorption factor. 

In many cases, toxicity observed via the dermal route will be different than toxicity observed via oral 

exposure, due to absorption and distribution of the toxic agent after exposure or differences in 

metabolism (i.e., systemic versus local). This means that the route-to-route extrapolation (i.e., use of an 

oral dose/endpoint) in risk assessment could result in under or over estimation of risks from the dermal 

route. 

How could the data impact the Agency’s future decision-making? 

If the dermal toxicity study indicates that tau-fluvalinate poses either a greater or lesser risk than that 

calculated using an oral dose, (as used in the interim decision), the risk assessment would be revised to 

reflect the magnitude of potential risk derived from the new data. Also, the requested data would allow 

the Agency to determine if the risks were over-estimated or under-estimated. If the risks were underestimated, additional risk mitigation measures could be required. If the risks were over-estimated, risk 

mitigation measures could be reduced. 

Guideline Number: 870.3465 

Study Title: 90-Day/28-Day Inhalation Toxicity 

Rationale for Requiring the Data 

Instead of conducting the inhalation study for 90-days, the Agency only needs a 28-day inhalation study 

because only short- and intermediate-term (but not long-term) exposure to workers is expected based on 

tau-fluvalinate's use pattern. A longer-term inhalation study is required in situations in which a specific 

concern exists for increased hazard related to exposure via the inhalation route. The 28-day inhalation 

toxicity study evaluates the potential hazard of a pesticide chemical following repeated inhalation 

exposures. This study is critical for pesticides with use patterns in which there is potential for repeated 

human exposures (e.g., professional applicators, green house use, etc.). The study design simulates the 

route of human exposure (inhalation). In this study, animals are exposed (nose/whole body) to aerosol 

concentrations of the test material for 6 hours/day, 5 days/week for 28 days. A detailed toxicological 

examination including the histopathology of the respiratory system is conducted. This route-specific study 

would provide data for hazard characterization, dose response assessment, and a dose and endpoint for 

assessing potential risks via the inhalation route. 

Practical Utility of the Data 

How will the data be used? 

This study will identify hazard (i.e., provide a dose and endpoint) following repeated inhalation exposures 

to tau-fluvalinate. The results will be used in risk assessments as appropriate. 

How could the data impact the Agency’s decision-making? 

A sub-chronic inhalation study provides critical scientific information needed to characterize potential 

hazard to the human respiratory system from tau-fluvalinate exposure. In the case of tau-fluvalinate, there 

is no acceptable inhalation study available. A 28-day repeated exposure study that follows the Test 

Guidelines (870.3465) will characterize hazard and provide data for a more refined inhalation risk 

assessment. Exposure time may be reduced 28 days pending exposure patterns, plateauing of effects and 

considering the overall toxicity potential of tau-fluvalinate. This requirement is pending resolution of 

inhalation exposure for existing and possible future uses. 
Page 19 of 27 

Guideline Number: 870.6200a 

Study Title: Acute Neurotoxicity Battery

Rationale for Requiring the Data 

This is a new data requirement under 40 CFR Part 158 as a part of the data requirements for registration 

of a pesticide (food and non-food uses). 

The Neurotoxicity Screening Battery (OPPTS 870.6200) is designed to evaluate the potential adverse 

effects on the nervous system from exposure to pesticide chemicals. The Agency believes that the 

guideline studies are inadequate in their assessment of behavioral effects and do not use optimal methods 

to evaluate the potential toxicity to the nervous tissue structure and function. To detect and characterize 

these potential effects more fully, a battery of more sensitive testing is required. The objective of this 

neurotoxicity battery testing is to evaluate the incidence and severity of the functional and/or behavioral 

effects, the level of motor activity, and the histopathology of the nervous system. The acute neurotoxicity

study is required to detect possible effects resulting from a single exposure. The sub-chronic 

neurotoxicity study is intended to detect possible effects resulting from repeated or long-term exposures. 

 

Practical Utility of the Data 

How will the data be used? 

The acute and sub-chronic neurotoxicity studies provide critical scientific information needed to 

characterize potential hazard to the human population on the nervous system from tau-fluvalinate 

exposure. These studies can provide data on a wide range of functional tests for evaluating neurotoxicity 

including sensory effects, neuromuscular effects, learning and memory and histopathology of the nervous 

system For example, animal studies with organophosphorous chemicals have shown neurotoxicity to be 

the primary toxic endpoints (e.g., cholinesterase inhibition) of concern in rodents and non-rodents. These 

animal studies can be used to select endpoints and doses for use in risk assessment of all exposure 

scenarios and are considered a primary data source for reliable reference dose calculation. The Agency 

has established an oral reference dose (RfD) for assessing dietary risks for a number of chemicals (e.g., 

organophoshates and carbamates) where neurotoxicity was the most sensitive endpoint of concern. 

How could the data impact the Agency's future decision-making? 

If the acute or sub-chronic neurotoxicity studies show that tau-fluvalinate poses either a greater or a 

diminished risk than that given in the interim decision’s conclusion, the risk assessment for taufluvalinate may need to be revised to reflect the magnitude of potential risk derived from the new data. 

 

If the Agency does not have this data, a 10X database uncertainty factor may be applied when conducting 

a risk assessment using the currently available studies. 

Guideline Number: 870.6300 

Study Title: Developmental Neurotoxicity Study 

Rationale for Requiring the Data 

Criteria have been developed for determining the need for a Developmental Neurotoxicity (DNT) study 

through extensive peer review, including review by the FIFRA Scientific Advisory Panel 

(http://www.epa.gov/scipoly/sap). The requirement for a DNT study typically is conditional, but the 

study may be required if acute oral, dermal, or inhalation studies showed neuropathy or neurotoxicity. 

For tau-fluvalinate, clinical signs of neurotoxicity and evidence of neuropathology have been observed 
Page 20 of 27 

in the guideline studies (i.e. tremors and ataxia). 

The reproduction study did not include an assessment of effects on the development of the nervous 

system. The required DNT study must be designed to evaluate the developing organism for functional 

and behavioral deficiencies and structural alterations to the nervous system, as may result from taufluvalinate exposure in utero or during early postnatal life. 

Practical Utility of the Data 

How did the Agency make its reregistration decision without these data? 

In part due to the absence of DNT data for tau-fluvalinate, the Agency may consider retaining a10X 

FQPA (Food Quality Protection Act) database uncertainty factor for the risk assessment. The 

uncertainty factor is expected to be protective for the sensitive population subgroups. 

How will the data be used and how could the data impact the Agency’s future decision-making? 

The DNT data will be used to characterize the neurotoxicity potential to infants and children, who may 

be more sensitive to the neurotoxic effects of tau-fluvalinate than adults. If review of the DNT study 

indicates that it is appropriate, and if other uncertainties are adequately addressed, the 10X database 

uncertainty factor, if applied, could be removed; therefore effectively reducing human health risk 

estimates by an order of magnitude. If the data indicate that infants and children are adversely affected 

by in utero exposure to tau-fluvalinate, or are more sensitive to tau-fluvalinate exposure in general, the 

Agency will consider choosing a new endpoint (from the DNT study) for the human health risk 

assessment of tau-fluvalinate. Results from the study will allow the Agency to make the necessary 

adjustments (if any) to risk mitigation measures resulting from the re-registration decision. 

Guideline Number: 870.7800 

Study Title: Immunotoxicity

Rationale for Requiring the Data 

This is a new data requirement under 40 CFR Part 158 as a part of the data requirements for registration 

of a pesticide (food and non-food uses). 

The Immunotoxicity Test Guideline (OPPTS 870.7800) prescribes functional immunotoxicity testing and 

is designed to evaluate the potential of a repeated chemical exposure to produce adverse effects (i.e., 

suppression) on the immune system. Immuno-suppression is a deficit in the ability of the immune system 

to respond to a challenge of bacterial or viral infections such as tuberculosis (TB), Severe Acquired 

Respiratory Syndrome (SARS), or neoplasia. Because the immune system is highly complex, studies 

assessing functional immunotoxic endpoints are helpful in fully characterizing a pesticide’s potential 

immunotoxicity. These data will be used in combination with data from hematology, lymphoid organ 

weights, and histopathology in routine chronic or sub-chronic toxicity studies to characterize potential 

immunotoxic effects. 

Practical Utility of the Data 

How will the data be used? 

These animal studies can be used to select endpoints and doses for use in risk assessment of all exposure 

scenarios and are considered a primary data source for reliable reference dose calculation. For example, 

animal studies have demonstrated that immunotoxicity in rodents is one of the more sensitive 

manifestations of TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) among developmental, reproductive, and 

endocrinologic toxicities. Additionally, the EPA has established an oral reference dose (RfD) for 

tributyltin oxide (TBTO) based on observed immunotoxicity in animal studies (IRIS, 1997). 
Page 21 of 27 

How could the data impact the Agency's future decision-making? 

If the immunotoxicity study shows that tau-fluvalinate poses either a greater or a diminished risk than that 

given in the interim decision’s conclusion, the risk assessments for tau-fluvalinate may need to be revised 

to reflect the magnitude of potential risk derived from the new data. 

 

If the Agency does not have this data, a 10X database uncertainty factor may be applied for conducting a 

risk assessment from the available studies. 
Page 22 of 27 

Appendix B: Tau-fluvalinate Toxicology 

Toxicological Doses and Endpoints used previously in the 2005 Tau-fluvalinate Human Risk 

Assessments

Exposure 

Scenario

Dose, Uncertainty Factors (UFs), 

and Safety Factors (SFs)

Population Adjusted 

Dose (PAD) or Target 

Margin of Exposure 

(MOE)

Study and Toxicological Effects

Tau-fluvalinate Dietary Exposures 

Acute Dietary 

(general 

population) 

NOAEL = 0.5 mg/kg/day 

UF = 100X (inter and intraspecies) 

FQPA SF = 1X (currently 

determined to be a 10x) 

Total UF = 100X 

Acute RfD = 0.005 mg/kg/day 

aPAD = Acute RfD

 FQPA SF 

aPAD = 0.005 

mg/kg/day 

LOAEL = 1 mg/kg/day. Clinical 

signs in the rat chronic feeding 

study coupled with a LOAEL of 2 

mg/kg/day based on excessive 

grooming and bulging eyes in the 

subchronic neurotoxicity study. 

Chronic Dietary 

(general 

population) 

NOAEL = 0.5 mg/kg/day 

UF = 100X (inter and intraspecies) 

FQPA SF = 1X (currently 

determined to be a 10x) 

Total UF = 100X 

cRfD = 0.005 mg/kg/day 

cPAD = Chronic RfD

 FQPA SF 

cPAD = 0.005 

mg/kg/day 

LOAEL = 1 mg/kg/day. Clinical 

signs in the rat chronic feeding 

study coupled with a LOAEL of 2 

mg/kg/day based on excessive 

grooming and bulging eyes in the 

sub-chronic neurotoxicity study. 

Tau-fluvalinate Dermal Exposures

Dermal - all 

intervals 

No endpoint selection. 
Page 23 of 27 

Toxicological Doses and Endpoints used previously in the 2005 Tau-fluvalinate Human Risk 

Assessments

Exposure 

Scenario

Dose, Uncertainty Factors (UFs), 

and Safety Factors (SFs)

Population Adjusted 

Dose (PAD) or Target 

Margin of Exposure 

(MOE)

Study and Toxicological Effects

Tau-fluvalinate Inhalation Exposures 

Inhalation 

(Short- and 

IntermediateTerm ) 

NOAEL = 0.5 mg/kg/day 

UF = 100X (inter and intraspecies) 

Total UF = 100X 

100% inhalation absorption 

assumed 

Occupational MOE = 

100 

LOAEL = 1 mg/kg/day. Clinical 

signs in the rat chronic feeding 

study coupled with a LOAEL of 2 

mg/kg/day based on excessive 

grooming and bulging eyes in the 

subchronic neurotoxicity study. 
Page 24 of 27 

Appendix C: Chemistry 

Tau-Fluvalinate Residue of Concern. 

Chemical structure 

Common name Tau-fluvalinate 

Molecular Formula C26H22ClF3N2O3

Molecular Weight 502.93 

IUPAC name (RS)-α-cyano-3-phenoxybenzyl N-(2-chloro-α,α,α-trifluoro-p-tolyl)-D-valinate 

CAS name cyano-(3-phenoxyphenyl)methyl N-[2-chloro-4-(trifluoromethyl)phenyl]-D-valinate 

CAS registry number 102851-06-9 (tau-fluvalinate) 

69409-94-5 (unresolved fluvalinate) 

PC Code 109302 

Physiochemical Properties of Tau-Fluvalinate

Parameter Value Reference 

Boiling point 164 °C at 0.07 mm Hg D165590, 3/4/92, F. Toghrol 

pH Not applicable; fluvalinate is practically 

insoluble in water 

Density, bulk density, or 

specific gravity 1.262 g/mL at 25 °C D165590, 3/4/92, F. Toghrol 

Water solubility 2.4 ppb at 25 °C D272832 and D273228, 3/21/01, 

K. Dockter 

Solvent solubility at 25 °C 

55.31 g/100 mL, methanol 

24.05 g/100 mL, octanol 

Miscible at all levels in isooctane, toluene, 

acetonitrile, 2-propanol, dimethylformamide, 

and 1-octanol 

D272832 and D273228, 3/21/01, 

K. Dockter 

D165590, 3/4/92, F. Toghrol 

Vapor pressure <1.0 x 10-5 Pa, 25 °C D272832 and D273228, 3/21/01, 

K. Dockter 

Dissociation constant, pKa

Not applicable due to the instability of 

fluvalinate under acidic and basic conditions, 

and its extremely low water solubility. 

Phase 4 Review, 1/16/91 

Octanol/water partition 

coefficient POW >106

, 25 °C D272832 and D273228, 3/21/01, 

K. Dockter 
Page 25 of 27 

Physiochemical Properties of Tau-Fluvalinate

Parameter Value Reference 

UV/visible absorption spectrum 

Acidic Methanol Medium: 

 255.5 nm (ε 19410 L/(mol • cm)) 

Neutral Methanol Medium: 

255.5 nm (ε 18597 L/(mol • cm)) 

Basic Methanol Medium: 

254.5 (ε 27732 L/(mol • cm)) 

297.5 (ε 5566 L/(mol • cm)) 

D321133, S.B. Mathur, 9/7/05 
Page 26 of 27 

Appendix D: Tau-fluvalinate Products 

Tau-fluvalinate Formulated Products 

Product EPA Reg. Number % Active Ingredient 

(tau-fluvalinate)

Technical (MUP) 2724-481 93.7 % 

Impregnated strip 2724-406 10.25 % 

Flowable concentrate 2724-478 22.3 % 

Co-formulated Product (Imidacloprid + 

Tau-fluvalinate + Tebuconazole) Ready 

to Use Liquid Concentrate 

72155-71 

0.0143 % 

Co-formulated Product (Imidacloprid + 

Tau-fluvalinate + Tebuconazole) Ready 

to Use Spray 

72155-73 

0.61 % 

Flowable concentrate CA04002200 22.3 % 

Flowable concentrate CA96001000 22.3 % 
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Appendix E: International Residue Limits 

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition: 

US Canada Mexico2 Codex3 

40 CFR 180.427:

Plant: Tau-fluvalinate [cyano-(3-

phenoxyphenyl)methyl N-[2-chloro-4-

(trifluoromethyl)phenyl]-D-valinate]

None None

Tolerance (ppm) /Maximum Residue Limit (mg/kg) Commodity1 

US Canada Mexico2 Codex 

Honey 0.02 

 

Completed: M. Negussie; 09/07/2010 

1

 Includes only commodities of interest for this action. Tolerance values should be the HED recommendations and 

not those proposed by the applicant. 

2 Mexico adopts US tolerances and/or Codex MRLs for its export purposes. 

3 * = absent at the limit of quantitation; Po = postharvest treatment, such as treatment of stored grains. PoP = 

processed postharvest treated commodity, such as processing of treated stored wheat. (fat) = to be measured on the 

fat portion of the sample. MRLs indicated as proposed have not been finalized by the CCPR and the CAC.