Page 2 of 8

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 duri ng registration review pending the outcome of that work

.

Hazard Identification/Toxicology The toxicity database for t e f l uthrin 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 inh alation 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 pyrethr oids 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. T efluthrin was also presented to the HED’s Cancer Assessment Review

Committee in 2012 ( J. Kidwell; TXR 0056340; 2012) and was cla ssified 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 acut e, 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 o n 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

st atutorily 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 s creening 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 d esigned 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.Page 3 of 8

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

O ctober 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 te f luthrin in plants and animals has been adequately

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

for tolerance enforcement and risk assessment are te f luthrin 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 p pm) 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 95 th
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 dietar y risk estimates from the 2012

risk assessment are below HED’s level of concern.

T here 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, o ccupational

post

- application exposure is expected to be negligible. No ne w occupational handler or

post

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

HED updated the occupational handler exposure assessment s for the 2012 Section 3 sugar beet seed tefluthrin risk assessment ( C. Smith; D 368331; 05/24/2012) . ThisPage 4 of 8

assessment includes an updated hazard assessment to reflect current py rethroid hazard information as well as updated occupational exposure assessment pol icies.

The results of the occupational handler exposure assessment indicate that t here are potential risk estimates of concern for some uses of te f l uthrin

. 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

Lo ader/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 rel ies 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 Agenc y 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 Huma n Subjects"

R egulation to reliance on these studies.

P ublic Health and Pesticide Epidemiology Data An updat ed review of tefluthrin incident reports was rec ently prepared by HED (S.

Recore , D 40 09 9 0

, 05/0 3 /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 teflut hrin 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 allegati ons 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,Page 5 of 8

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 ev aluated 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 no t 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), c alculated 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 Low

Income Populations," http://www.epa.gov/compliance/resources/p olicies/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 d rinking 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 assessment s 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 ofPage 6 of 8

the pyrethroid/pyrethrin common mechanism group ( http://www.regulations.gov ; EPA

HQ

- 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 c umulative 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/pyrethroids

pyrethrins.html

.

Data Requirements HED does not anticipate that additional residue chemistry, toxicology or occupational/residential exposure data will be r equired 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 re view.Page 7 of 8 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

.............. 870.539 5 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 Neurotox icity (Hen)

................................ ....... 87 0.6100 90

- Day Neurotoxicity (Hen)

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

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

................................ .. 870.6300 Develop mental Neuro toxicity

................................ ................ 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 ; 2012Page 8 of 8

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)

Commodit

y 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 D 400990 05/03/2012 Tefluthrin: Review of Human

Incidents

J. Kidwell TXR

0056340 2012 Tefluthrin : Report of the Cancer

Assessment Review Committee