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uses of tefluthrin. The Agency is currently working with Syngenta to address the 

occupational handler risks of concern identified in the 2012 human health risk 

assessment. HED may need to update the occupational tefluthrin risk assessment during 

registration review pending the outcome of that work.

Hazard Identification/Toxicology

The toxicity database for tefluthrin is complete for risk assessment purposes (see Table 

1). No additional data are required during the registration review process. HED updated 

the hazard characterization for the 2012 tefluthrin risk assessment to reflect current 

policies. Tefluthrin is acutely toxic (category I) via the oral, dermal, and inhalation 

routes of exposure but it is not classified as a skin sensitizer or ocular irritant. No 

reproductive or developmental effects were observed in tefluthrin toxicity studies using 

rats and rabbits. Behavioral changes characteristic of Type I pyrethroids such as 

unsteadiness, tremors, and ataxia were observed in the guideline rat, dog, and rabbit 

toxicological studies. Consistent with the general toxicological profile of the pyrethroids, 

these effects were generally seen quickly after dosing and thus, for purposes of endpoint 

selection and exposure assessment, only single day risk assessments were conducted for 

tefluthrin. Tefluthrin was also presented to the HED’s Cancer Assessment Review 

Committee in 2012 (J. Kidwell; TXR 0056340; 2012) and was classified as “not likely to 

be a human carcinogen.

Endocrine Disruption Screening Program

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential 

adverse outcomes from exposure to chemicals. Collectively, these studies include acute, 

subchronic and chronic toxicity, including assessments of carcinogenicity, neurotoxicity, 

developmental, reproductive, and general or systemic toxicity. These studies include 

endpoints which may be susceptible to endocrine influence, including effects on 

endocrine target organ histopathology, organ weights, estrus cyclicity, sexual maturation, 

fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological 

hazard assessments, EPA evaluates acute tests and chronic studies that assess growth, 

developmental and reproductive effects in different taxonomic groups. As part of its 

reregistration decision, EPA reviewed these data and selected the most sensitive 

endpoints for relevant risk assessment scenarios from the existing hazard database. 

However, as required by FFDCA section 408(p), metribuzin is subject to the endocrine 

screening part of the Endocrine Disruptor Screening Program (EDSP). 

EPA has developed 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 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.
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Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. 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. 

Tefluthrin is not among the group of 58 pesticide active ingredients on the initial list to be 

screened under the EDSP. Accordingly, as part of registration review, EPA will issue 

future EDSP orders/data call-ins, requiring the submission of EDSP screening assays for

nitrapyrin. For further information on the status of the EDSP, the policies and 

procedures, the list of 67 chemicals, future lists, the test guidelines and the Tier 1 

screening battery, please visit our website: http://www.epa.gov/endo/.

Residue Chemistry

The existing residue chemistry database for tefluthrin is adequate for risk assessment 

purposes. No additional data are required during the registration review process. The 

qualitative nature of the residue(s) of tefluthrin in plants and animals has been adequately 

identified/characterized and is understood. The residues of concern in plants and animals 

for tolerance enforcement and risk assessment are tefluthrin and its metabolite PP 890. 

Dietary Exposure and Risk Assessment

The tefluthrin dietary exposure database is adequate to support the existing registrations. 

For the 2012 risk assessment, an unrefined acute dietary analysis was performed for 

tefluthrin that assumes 100% of the crops were treated and residues were at half the limit 

of quantitation (1/2 LOQ = 0.3 ppm) on all types of corn (the only registered food use). 

The results of acute aggregate dietary (food + drinking water) analysis show that the 

acute dietary risk for the general U.S. population and all population subgroups are below 

HED’s level of concern (<100% acute Population Adjusted Dose (aPAD)) at the 95th

percentile of the exposure distribution.

Residential Exposure and Risk Assessment

There are currently no registered residential uses associated with tefluthrin; therefore, a 

residential/non-occupational exposure assessment is not required.

Aggregate Exposure and Risk Assessment

Since there are no residential uses of tefluthrin, acute aggregate risks are equivalent to 

estimated acute dietary (food and water) risks. The dietary risk estimates from the 2012 

risk assessment are below HED’s level of concern.

There are currently no registered residential uses associated with tefluthrin and therefore 

a short-term aggregate risk assessment is not required.

Occupational Exposure and Risk Assessment

The occupational exposure database is adequate for risk assessment purposes. Based on 

the current use pattern, occupational handler exposure is expected, however, occupational 

post-application exposure is expected to be negligible. No new occupational handler or 

post-application worker studies are needed during the registration review process. 

HED updated the occupational handler exposure assessments for the 2012 Section 3 

sugar beet seed tefluthrin risk assessment (C. Smith; D368331; 05/24/2012). This 
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assessment includes an updated hazard assessment to reflect current pyrethroid hazard 

information as well as updated occupational exposure assessment policies.

The results of the occupational handler exposure assessment indicate that there are 

potential risk estimates of concern for some uses of tefluthrin. The estimated risks 

exceed HED’s level of concern for the following scenarios: 

Mixer/loaders for the granular corn at-plant product unless engineering 

controls are utilized, and

Loader/applicators, handlers performing multiple activities, and handlers 

performing equipment cleaning activities for the corn seed treatment use 

for open and closed system seed treatment systems.

There are no risk estimates of concern for the other uses of tefluthrin.

The Agency is currently working with Syngenta to address the occupational handler risks 

of concern identified in the 2012 human health risk assessment. HED may need to 

update the occupational tefluthrin risk assessment during registration review pending the 

outcome of that work.

Human Studies

The 2012 tefluthrin risk assessment relies in part on data from studies in which adult 

human subjects were intentionally exposed to a pesticide or other chemical. Studies such 

as the Pesticide Handlers Exposure Database, the Agricultural Handler Exposure Task 

Force, and studies included in the Seed Treatment SOPs as well as a proprietary seed 

treatment exposure study (MRID 45200002) have been reviewed by the Agency and 

found on the basis of available evidence to have been neither fundamentally unethical nor 

significantly deficient relative to standards of ethical research conduct prevailing when 

they were conducted. There is no barrier in EPA's "Protection of Human Subjects" 

Regulation to reliance on these studies.

Public Health and Pesticide Epidemiology Data

An updated review of tefluthrin incident reports was recently prepared by HED (S. 

Recore, D400990, 05/03/2012). For this evaluation, the OPP Incident Data System (IDS) 

was consulted for pesticide incident data on the active ingredient tefluthrin. Tefluthrin is 

not included in the Agricultural Health Study (AHS) and therefore no information from 

the AHS on tefluthrin is included in the HED incident report.

The IDS includes reports of alleged human health incidents from various sources, 

including mandatory Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) 

Section 6 (a) (2) reports from registrants, other federal and state health and environmental 

agencies and individual consumers. IDS contain reports from across the U.S. and most 

incidents have all relevant product information recorded. Reports submitted to the IDS 

represent anecdotal reports or allegations only, unless otherwise stated in the report. IDS 

records incidents resulting in higher severity outcomes in more detail, in a module called 

the Main IDS module. This system stores incident data for death, major and moderate 

incidents, and it includes more details about the location, date and nature of the incident.

In Aggregate IDS, from January 1, 2007 to February 22, 2012, there were 21 reported 

incidents involving tefluthrin. For the Main IDS, from January 1, 2007 to February 22, 
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2012, there were six incidents reported in the database. One incident was classified as 

major severity, four incidents were classified as moderate severity, and there was one 

death. Overall, there are few incidents involving tefluthrin reported to IDS. 

HED further evaluated the incident resulting in death as well as the major severity 

incident and neither of these is likely to be related to the active ingredient tefluthrin. 

Based on the overall low frequency and generally low severity of incident cases, there 

does not appear to be a concern for tefluthrin at this time that would warrant further 

investigation. The Agency will continue to monitor the incident information and 

additional analysis will be performed during registration review if a concern is triggered 

for tefluthrin.

Tolerance Assessment and International Harmonization

Tolerances are established under 40 CFR §180.440 for residues of tefluthrin, including its 

metabolites and degradates, in or on field corn, popcorn, and sweet corn. The Codex 

Alimentarius Commission, Canada’s Pest Management Regulatory Agency (PMRA), and 

Mexico have not established maximum residue limits (MRLs) for tefluthrin (see Table 2).

The current tolerance expression as listed in the 40 CFR§180.440 (a) has not been 

updated to reflect current HED policies and thus will need to be revised during the 

registration review process. The revised tolerance expression should be as follows: 

Tolerances are established for residues of the insecticide tefluthrin, including its 

metabolites and degradates, in or on the registered commodities. Compliance 

with the tolerance levels is to be determined by measuring only the sum of 

tefluthrin [(2,3,5,6 tetrafluoro-4-methylphenyl)methyl-(1 alpha, 3 alpha)-(Z)-(±)-

3(2-chloro-3,3,3-trifluoro-1-propenyl)-2,2-dimethylcyclopropanecarboxylate] and 

its metabolite PP 890 ((Z)-3-(2-chloro-3,3,3-trifluroro-1-propenyl)-2,2-

dimethylcyclopropane carboxylic acid), calculated as the stoichiometric 

equivalent of tefluthrin, in or on the commodity.

Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, were considered 

in this human health risk assessment, in accordance with U.S. Executive Order 12898, 

"Federal Actions to Address Environmental Justice in Minority Populations and LowIncome 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 high exposures indicate potential risks of concern, OPP will further 

refine the risk assessments to ensure that the risk estimates are based on the best available 

information.

Cumulative Risk Assessment

The Food Quality Protection Act (FQPA) requires the Agency to consider the cumulative 

risks of chemicals sharing a common mechanism of toxicity. Tefluthrin is a member of 
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the pyrethroid/pyrethrin common mechanism group (http://www.regulations.gov; EPAHQ-OPP-2008-0489-0006). The members of this group share the ability to interact with 

voltage-gated sodium channels ultimately leading to neurotoxicity. The cumulative risk 

assessment for the pyrethroids/pyrethrins was published on Nov. 9, 2011 and is available 

at http://www.regulations.gov; EPA-HQ-OPP-2011-0746. No cumulative risk estimates 

of concern were identified allowing the Agency to consider new uses for pyrethroid 

actives. For information regarding EPA’s efforts to evaluate the risk of exposure to 

pyrethroids, refer to http://www.epa.gov/oppsrrd1/reevaluation/pyrethroidspyrethrins.html. 

Data Requirements

HED does not anticipate that additional residue chemistry, toxicology or 

occupational/residential exposure data will be required for the tefluthrin registration 

review process.

Barring submission of any data that would impact the outcome of the May 2012 risk

assessment, HED does not anticipate the need for any updates to the tefluthrin risk 

assessment during registration review.
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Table 1: Toxicological Studies Available for Tefluthrin

Guideline Number and Toxicity Study Required Satisfied

870.1100 Acute Oral Toxicity................................................................

870.1200 Acute Dermal Toxicity...........................................................

870.1300 Acute Inhalation Toxicity.......................................................

870.2400 Primary Eye Irritation.............................................................

870.2500 Primary Dermal Irritation.......................................................

870.2600 Dermal Sensitization ..............................................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.3100 Oral Sub-chronic (Rodent).....................................................

870.3150 Oral Sub-chronic (Non-Rodent).............................................

870.3200 21-Day Dermal.......................................................................

870.3250 90-Day Dermal.......................................................................

870.3465 90/28-Day Inhalation..............................................................

yes

yes

yes

no

yes

yes

yes

yes

no

yes

870.3700 Developmental Toxicity (Rodent).........................................

870.3700 Developmental Toxicity (Non-rodent)...................................

870.3800 Reproduction..........................................................................

yes

yes

yes

yes

yes

yes

870.4100 Chronic Toxicity (Rodent) .....................................................

870.4100 Chronic Toxicity (Non-rodent)...............................................

870.4200 Oncogenicity (Rat).................................................................

870.4200 Oncogenicity (Mouse)............................................................

870.4300 Chronic/Oncogenicity ............................................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.5100 Mutagenicity: Gene Mutation - bacterial................................

870.5300 Mutagenicity: Gene Mutation - mammalian...........................

870.5375 Mutagenicity: Structural Chromosomal Aberrations..............

870.5395 Mutagenicity: Structural Chromosomal Aberrations..............

870.5500 Mutagenicity: Other Genotoxic Effects..................................

870.5550 Mutagenicity: Other Genotoxic Effects..................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

no

870.6100 Acute Delayed Neurotoxicity (Hen).......................................

870.6100 90-Day Neurotoxicity (Hen) ..................................................

870.6200 Acute Neurotoxicity Screening Battery (Rat).........................

870.6200 90 Day Neuro. Screening Battery (Rat)..................................

870.6300 Developmental Neurotoxicity ................................................

CR

CR

yes

yes

no

yes

--

yes 1

yes 1

no

870.7485 General Metabolism...............................................................

870.7600 Dermal Penetration.................................................................

870.7800 Immunotoxicity.......................................................................

yes

CR

yes

yes

yes

yes

--Not applicable

1 K. Rury; TXR 0056311; 2012
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Table 2: Summary of US and International Tolerances and Maximum Residue 

Limits for Tefluthrin

Residue Definition:

US Canada Mexico Codex

40 CFR 180.440:

Plant: tefluthrin [(2,3,5,6 tetrafluoro-4-

methylphenyl)methyl-(1 alpha, 3 alpha)-

(Z)-(±)-3(2-chloro-3,3,3-trifluoro-1-

propenyl)-2,2-

dimethylcyclopropanecarboxylate] and its 

metabolite PP 890 ((Z)-3-(2-chloro-3,3,3-

trifluroro-1-propenyl)-2,2-

dimethylcyclopropane carboxylic acid)

Commodity

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

US Canada Mexico Codex

Corn, field, forage 0.06

Corn, field, grain 0.06

Corn, field, stover 0.06

Corn, pop, grain 0.06

Corn, pop, stover 0.06

Corn, sweet, forage 0.06

Corn, sweet, kernel plus cob 

with husks removed 0.06

Corn, sweet, stover 0.06

Completed: Name/Date

Table 3: HED Memoranda Relevant to Registration Review

Author Barcode/TXR # Date Title

C. Smith D368331 05/24/2012 Tefluthrin: Human Health Risk 

Assessment for Proposed Section 3 

Registration on Sugar Beet Seed 

(Non-Food Use).

K. Rury TXR 0056311 05/31/2012 Tefluthrin: Summary of Hazard and 

Science Policy Council (HASPOC) 

Meetings: Recommendations on the 

need for neurotoxicity battery (acute 

and subchronic). 

S. Recore D400990 05/03/2012 Tefluthrin: Review of Human 

Incidents

J. Kidwell TXR 

0056340

2012 Tefluthrin: Report of the Cancer 

Assessment Review Committee