United States			Prevention, Pesticides		EPA  OPP-2005-0293	 Environmental Protection 		And Toxic Substances		June 14, 2006

			Agency				(7508C)

			_________________________________________________________________

  SEQ CHAPTER \h \r 1 Reregistration Eligibility    Decision for Cypermethrin

List B

Case No. 2130

  SEQ CHAPTER \h \r 1

TABLE OF CONTENTS

  TOC \o "1-5" \h \z \u    HYPERLINK \l "_Toc142818366"  Cypermethrin Reregistration Eligibility Decision Team	  PAGEREF _Toc142818366 \h  5

  HYPERLINK \l "_Toc142818367"  Glossary of Terms and Abbreviations	  PAGEREF _Toc142818367 \h  6

  HYPERLINK \l "_Toc142818368"  Executive Summary	  PAGEREF _Toc142818368 \h  8

  HYPERLINK \l "_Toc142818369"  I.	Introduction	  PAGEREF _Toc142818369 \h  14

  HYPERLINK \l "_Toc142818370"  II.	Chemical Overview	  PAGEREF _Toc142818370 \h  15

  HYPERLINK \l "_Toc142818371"  A.	Regulatory History	  PAGEREF _Toc142818371 \h  15

  HYPERLINK \l "_Toc142818372"  B.	Chemical Identification	  PAGEREF _Toc142818372 \h  16

  HYPERLINK \l "_Toc142818373"  C.	Use Profiles	  PAGEREF _Toc142818373 \h  17

  HYPERLINK \l "_Toc142818374"  III.	Summary of Cypermethrin Risk Assessments	  PAGEREF _Toc142818374 \h  18

  HYPERLINK \l "_Toc142818375"  A.	Human Health Risk Assessment	  PAGEREF _Toc142818375 \h  19

  HYPERLINK \l "_Toc142818376"  1.	Toxicity	  PAGEREF _Toc142818376 \h  19

  HYPERLINK \l "_Toc142818377"  2.	FQPA Safety Factor	  PAGEREF _Toc142818377 \h  21

  HYPERLINK \l "_Toc142818378"  3.	Dermal Absorption	  PAGEREF _Toc142818378 \h  22

  HYPERLINK \l "_Toc142818379"  4.	Dietary Exposure	  PAGEREF _Toc142818379 \h  22

  HYPERLINK \l "_Toc142818380"  a.	Acute Dietary Exposure (food only)	  PAGEREF _Toc142818380 \h  22

  HYPERLINK \l "_Toc142818381"  b.	Chronic Dietary Exposure (food only)	  PAGEREF _Toc142818381 \h  23

  HYPERLINK \l "_Toc142818382"  5.	Drinking Water Exposure	  PAGEREF _Toc142818382 \h  23

  HYPERLINK \l "_Toc142818383"  6.	Residential Exposure and Risk	  PAGEREF _Toc142818383 \h  23

  HYPERLINK \l "_Toc142818384"  a.	Residential Handler Risk	  PAGEREF _Toc142818384 \h  24

  HYPERLINK \l "_Toc142818385"  b.	Residential Post-application Risk	  PAGEREF _Toc142818385 \h  24

  HYPERLINK \l "_Toc142818386"  7.	Aggregate Exposure and Risk (food, drinking water, and residential)	  PAGEREF _Toc142818386 \h  25

  HYPERLINK \l "_Toc142818387"  a.	Acute Aggregate Risk (food and drinking water)	  PAGEREF _Toc142818387 \h  25

  HYPERLINK \l "_Toc142818388"  b.	Short-term Aggregate Risk (food, drinking water, and residential)	  PAGEREF _Toc142818388 \h  26

  HYPERLINK \l "_Toc142818389"  c.	Chronic Aggregate Risk (food and drinking water)	  PAGEREF _Toc142818389 \h  26

  HYPERLINK \l "_Toc142818390"  8.	Occupational Exposure and Risk	  PAGEREF _Toc142818390 \h  26

  HYPERLINK \l "_Toc142818391"  a.	Occupational Handler Risk	  PAGEREF _Toc142818391 \h  27

  HYPERLINK \l "_Toc142818392"  b.	Occupational Post-application Risk	  PAGEREF _Toc142818392 \h  28

  HYPERLINK \l "_Toc142818393"  9.	Human Incident Data	  PAGEREF _Toc142818393 \h  28

  HYPERLINK \l "_Toc142818394"  B.	Environmental Risk Assessment	  PAGEREF _Toc142818394 \h  29

  HYPERLINK \l "_Toc142818395"  1.	Environmental Fate and Transport	  PAGEREF _Toc142818395 \h  29

  HYPERLINK \l "_Toc142818396"  2.	Ecological Risk	  PAGEREF _Toc142818396 \h  30

  HYPERLINK \l "_Toc142818397"  a.	Risk to Aquatic Organisms	  PAGEREF _Toc142818397 \h  30

  HYPERLINK \l "_Toc142818398"  b.	Risk to Terrestrial Organisms	  PAGEREF _Toc142818398 \h  37

  HYPERLINK \l "_Toc142818399"  c.	Ecological Incidents	  PAGEREF _Toc142818399 \h  39

  HYPERLINK \l "_Toc142818400"  d.	Endangered Species Concerns	  PAGEREF _Toc142818400 \h  39

  HYPERLINK \l "_Toc142818401"  IV.	Risk Management, Reregistration, and Tolerance Reassessment Decision	  PAGEREF _Toc142818401 \h  41

  HYPERLINK \l "_Toc142818402"  A.	Determination of Reregistration Eligibility and Tolerance Reassessment	  PAGEREF _Toc142818402 \h  41

  HYPERLINK \l "_Toc142818403"  B.	Public Comments and Responses	  PAGEREF _Toc142818403 \h  41

  HYPERLINK \l "_Toc142818404"  C.	Regulatory Position	  PAGEREF _Toc142818404 \h  42

  HYPERLINK \l "_Toc142818405"  1.	Food Quality Protection Act Findings	  PAGEREF _Toc142818405 \h  42

  HYPERLINK \l "_Toc142818406"  2.	Endocrine Disruptor Effects	  PAGEREF _Toc142818406 \h  43

  HYPERLINK \l "_Toc142818407"  3.	Cumulative Risks	  PAGEREF _Toc142818407 \h  43

  HYPERLINK \l "_Toc142818408"  D.	Tolerance Reassessment Summary	  PAGEREF _Toc142818408 \h  44

  HYPERLINK \l "_Toc142818409"  E.	Regulatory Rationale	  PAGEREF _Toc142818409 \h  45

  HYPERLINK \l "_Toc142818410"  1.	Human Health Risk Mitigation	  PAGEREF _Toc142818410 \h  46

  HYPERLINK \l "_Toc142818411"  2.	Environmental Risk Mitigation	  PAGEREF _Toc142818411 \h  48

  HYPERLINK \l "_Toc142818412"  3.	Benefits of Cypermethrin Use and Available Alternatives	  PAGEREF _Toc142818412 \h  56

  HYPERLINK \l "_Toc142818413"  V.	What Registrants Need to Do	  PAGEREF _Toc142818413 \h  56

  HYPERLINK \l "_Toc142818414"  A.	Manufacturing Use Products	  PAGEREF _Toc142818414 \h  57

  HYPERLINK \l "_Toc142818415"  1.	Additional Generic Data Requirements	  PAGEREF _Toc142818415 \h  57

  HYPERLINK \l "_Toc142818416"  2.	Labeling Requirements	  PAGEREF _Toc142818416 \h  57

  HYPERLINK \l "_Toc142818417"  3.	Spray Drift Management	  PAGEREF _Toc142818417 \h  57

  HYPERLINK \l "_Toc142818418"  B. 	End-Use Products	  PAGEREF _Toc142818418 \h  57

  HYPERLINK \l "_Toc142818419"  1.    Additional Product-Specific Data Requirements	  PAGEREF _Toc142818419 \h  57

  HYPERLINK \l "_Toc142818420"  2.    Labeling for End-Use Products	  PAGEREF _Toc142818420 \h  58

  HYPERLINK \l "_Toc142818421"  Appendix A. Uses of Cypermethrin Eligible for Reregistration	  PAGEREF _Toc142818421 \h  77

  HYPERLINK \l "_Toc142818422"  Appendix B.  Table of Generic Data Requirements and Studies Used to Make the Reregistration Decision for Cypermethrin	  PAGEREF _Toc142818422 \h  85

  HYPERLINK \l "_Toc142818423"  APPENDIX C:  Technical Support Documents   PAGEREF _Toc142818423 \h  91

  HYPERLINK \l "_Toc142818424"  Appendix D. 	Citations Considered to be Part of the Data Base Supporting the Reregistration Eligibility Decision   PAGEREF _Toc142818424 \h  93

  HYPERLINK \l "_Toc142818425"  APPENDIX E:  Generic Data Call-In	  PAGEREF _Toc142818425 \h  113

  HYPERLINK \l "_Toc142818426"  APPENDIX F:  Product Specific Data Call-In	  PAGEREF _Toc142818426 \h  114

Cypermethrin Reregistration Eligibility Decision Team

Office of Pesticide Programs:

Environmental Fate and Effects Risk Assessment

  SEQ CHAPTER \h \r 1 Miachel Rexrode

José Luis Meléndez

Health Effects Risk Assessment

  SEQ CHAPTER \h \r 1 William H. Donovan

Pamela M. Hurley

  SEQ CHAPTER \h \r 1 John Doherty

Seyed Tadayon

Biological and Economic Analysis Division

Alan Halvorson

Registration

George LaRocca

Risk Management

Yan Donovan

Véronique LaCapra

Dirk V. Helder

  SEQ CHAPTER \h \r 1 Glossary of Terms and Abbreviations  TC "Glossary of Terms and Abbreviations" \f C \l "1"

AGDCI		Agricultural Data Call-In

ai			Active Ingredient

aPAD			Acute Population Adjusted Dose

AR			Anticipated Residue

BCF			Bioconcentration Factor

CFR			Code of Federal Regulations

cPAD			Chronic Population Adjusted Dose

CSF			Confidential Statement of Formula

CSFII			USDA Continuing Surveys for Food Intake by Individuals

DCI			Data Call-In

DEEM			Dietary Exposure Evaluation Model

DFR			Dislodgeable Foliar Residue

DWLOC		Drinking Water Level of Comparison.

EC			Emulsifiable Concentrate Formulation

EDWC			Estimated Drinking Water Concentration

EEC			Estimated Environmental Concentration

EPA			Environmental Protection Agency

EUP			End-Use Product

FDA			Food and Drug Administration

FIFRA			Federal Insecticide, Fungicide, and Rodenticide Act

FFDCA	Federal Food, Drug, and Cosmetic Act

FQPA			Food Quality Protection Act

FOB			Functional Observation Battery

G			Granular Formulation

GENEEC		Tier I Surface Water Computer Model

GLN			Guideline Number

HAFT			Highest Average Field Trial

IR			Index Reservoir

LC50			Median Lethal Concentration.  A statistically derived concentration of a substance that can be expected to cause death in 50% of test animals.  It is usually expressed as the weight of substance per weight or volume of water, air or feed, e.g., mg/l, mg/kg or ppm.

LD50			Median Lethal Dose.  A statistically derived single dose that can be expected to cause death in 50% of the test animals when administered by the route indicated (oral, dermal, inhalation).  It is expressed as a weight of substance per unit weight of animal, e.g., mg/kg.

LOC			Level of Concern

LOD			Limit of Detection

LOAEL		Lowest Observed Adverse Effect Level

MATC			Maximum Acceptable Toxicant Concentration

g/g			Micrograms Per Gram

g/L			Micrograms Per Liter

mg/kg/day		Milligram Per Kilogram Per Day

mg/L			Milligrams Per Liter

MOE			Margin of Exposure

MRID			Master Record Identification (number).  EPA's system of recording and tracking studies submitted.

MUP			Manufacturing-Use Product

NA			Not Applicable

NAWQA		USGS National Water Quality Assessment

NPDES		National Pollutant Discharge Elimination System

NR			Not Required

NOAEC			No Observed Adverse Effect Concentration

NOAEL		No Observed Adverse Effect Level

OP			Organophosphate

OPP			EPA Office of Pesticide Programs

OPPTS			EPA Office of Prevention, Pesticides and Toxic Substances

PAD			Population Adjusted Dose

PCA			Percent Crop Area

PDP			USDA Pesticide Data Program

PHED			Pesticide Handler's Exposure Data

PHI			Preharvest Interval

ppb			Parts Per Billion

PPE			Personal Protective Equipment

ppm			Parts Per Million

PRZM/EXAMS		Tier II Surface Water Computer Model

Q1*			The Carcinogenic Potential of a Compound, Quantified by the EPA's Cancer Risk Model

RAC			Raw Agriculture Commodity

RED			Reregistration Eligibility Decision

REI			Restricted Entry Interval

RfD			Reference Dose

RQ			Risk Quotient

SCI-GROW		Tier I Ground Water Computer Model

SAP			Science Advisory Panel

SF			Safety Factor

SLC			Single Layer Clothing

SLN			Special Local Need  (Registrations Under Section 24(c) of FIFRA)

TGAI			Technical Grade Active Ingredient

TRR			Total Radioactive Residue

USDA			United States Department of Agriculture

USGS			United States Geological Survey

UF			Uncertainty Factor

UV			Ultraviolet

WPS			Worker Protection Standard

  SEQ CHAPTER \h \r 1  Executive Summary

This document presents EPA’s decision regarding the reregistration eligibility of the registered uses of cypermethrin.   The Agency has conducted human health and ecological risk assessments based on reviews of the database supporting use patterns of the currently registered cypermethrin products.  This document summarizes these risk assessments and describes the mitigation measures needed to address the identified risks.

Cypermethrin is an insecticide used both in agricultural and non-agricultural settings.  Total cypermethrin use in the United States is approximately 1.0 million pounds of active ingredient (a.i.) per year.  Approximately 140,000 pounds a.i. are used in agricultural crops, mainly on cotton (110,000 pounds), with minor uses on pecans, peanuts, broccoli and sweet corn.  Treatment of cattle and other livestock accounts for approximately 1000 pounds a.i. per year.  The great majority of cypermethrin use occurs in non-agricultural settings, including a wide range of commercial, industrial, and residential sites.  Indoor pest control -mainly for control of ants, cockroaches, and fleas - accounts for about 110,000 pounds a.i., while outdoor structural, perimeter, and turf uses for control of subterranean termites and other insect pests accounts for nearly 750,000 pounds a.i.  In residential settings, cypermethrin can be applied both by professional applicators and by residential users.

Cypermethrin was first registered in 1984 by FMC Corporation, who also subsequently registered the isomer enriched zeta-cypermethrin in 1992. Current technical registrants for cypermethrin included FMC, Syngenta, United Phosphorus International, and Valent BioSciences.  Data for the two active ingredients is considered interchangeable. Since zeta-cypermethrin was registered after 1984, only cypermethrin is subject to reregistration.  Cypermethrin is on reregistration List B; thus no Registration Standard was completed.  Data call-ins (DCIs) for cypermethrin were issued in 1991 for basic toxicology and residue chemistry data, and in 1995 for handler exposure and worker re-entry data.  Cypermethrin is one of nine synthetic pyrethroids registered on cotton, represented by the Pyrethroid Working Group (PWG), that are considered to be conditionally registered pending the development and review of data related to aquatic toxicity.  EPA will make every effort to coordinate the implementation of its reregistration eligibility decision provisions and labeling for cypermethrin with the ongoing efforts of the PWG.

  SEQ CHAPTER \h \r 1   SEQ CHAPTER \h \r 1 The Agency’s human health effects and environmental fate risk assessment for cypermethrin included the assessment for zeta-cypermethrin as well, since zeta-cypermethrin is an S-enantiomer enriched formulation of cypermethrin, which is not distinguished from cypermethrin by the analytical enforcement method, and the toxicological endpoints are the same for both cypermethrin and zeta-cypermethrin.

Human Health Risk

Dietary Exposure (food only)

  SEQ CHAPTER \h \r 1 Refined acute (probabilistic) and chronic dietary exposure assessments were performed in order to determine the dietary (food only) exposure and risk estimates which result from the use of cypermethrin and zeta-cypermethrin in/on all registered crops.    SEQ CHAPTER \h \r 1 Actual residues from USDA PDP monitoring data (collected during 1994, 1996, 1999, and 2001), estimated percent crop treated information, and processing factors, where available, were used.  For acute exposure,   SEQ CHAPTER \h \r 1 the most highly exposed population subgroup was children 1-2 years old at 6.1% of the aPAD at the 99.9th percentile.  For chronic exposure, the most highly exposed population subgroup was children 1-2 years old at 0.2% of the cPAD.  Dietary exposures (both acute and   SEQ CHAPTER \h \r 1 chronic) estimates are below the Agency’s level of concern for the general U.S. population and all population subgroups.

		Drinking Water Exposure

The Estimated Drinking Water Concentrations (EDWCs)ervoir, cotton, not brassicas?] te risks from food and drinking water  for cypermethrin were calculated   SEQ CHAPTER \h \r 1 using PRZM/EXAMS model (Tier II ), based on the highest seasonal application rate (0.6 lb a.i./A on cotton). The estimated acute drinking water concentration in surface water is 1.04 ppb, and the estimated chronic drinking water concentration in surface water is 0.013 ppb.  The SCI-GROW model was used to generate the EDWC for groundwater.  The groundwater EDWC for both acute and chronic exposures is 0.0036 ppb.

		Residential Exposure and Risk

Residential handler inhalation risks are below EPA’s level of concern for all non-occupational handler scenarios.  No short-term dermal exposures or risks were assessed for residential handlers since no dermal endpoints of concern were identified.  EPA does not anticipate that residential handlers would have intermediate- or long-term exposures to cypermethrin or zeta-cypermethrin.  Therefore, no intermediate- or long-term risks were assessed.

on-dietary post-application exposure to adults was assessed via the inhalation route, since no effects were observed in the dermal exposure study. Exposure to toddlers was assessed via the inhalation route, and via incidental oral exposure.  All of these exposures are considered short term.   Although cypermethrin can be used indoors as termiticide, long term exposure due to inhalation is considered negligible, since the vapor pressure for cypermethrin is extremely low.  Inhalation risks to both adults and toddlers were below the Agency’s level of concern.  Individually, risks from hand to mouth exposure, object to mouth exposure, and incidental soil ingestion were all below EPA’s level of concern.

Aggregate risk

An acute aggregate risk assessment was conducted taking into account risk from food and drinking water.  EPA calculated the Drinking Water Levels of Comparison (DWLOC, which represents the maximum allowable exposure from drinking water that would still fall below EPA’s level of concern) for all population subgroups.  The acute DWLOC for the most highly exposed population subgroup (children 1-2 years old) is 940 ppb, which is much higher than the peak EDWC of 1.04 ppb in surface water and the maximum EDWC for ground water of 0.0036 ppb; therefore, acute aggregate risk estimates associated with exposure to cypermethrin residues in food and water do not exceed EPA’s level of concern.

Short-term aggregate exposure takes into account residential exposure plus average exposure levels to food and water (considered to be a background exposure level).    SEQ CHAPTER \h \r 1 The calculated DWLOC value for children 1-2 years old is 890 ppb and this level is higher than the surface and ground water EDWCs of 0.013 and 0.0036 ppb.

Chronic aggregate assessment only includes food and water since chronic exposure from residential uses is negligible.  The highest exposed population subgroup (children 1-2 years old) has a DWLOC value of 600 ppb, which is greater than the average annual EDWCs of 0.013 ppb for surface water and 0.0036 ppb for ground water.   Therefore, chronic aggregate risk does not exceed the Agency’s level of concern.

Cumulative

Cypermethrin is a member of the pyrethroid class of pesticides.  Although all pyrethroids alter nerve function by modifying the normal biochemistry and physiology of nerve membrane sodium channels, available data shows that there are multiple types of sodium channels and that these compounds may act on different isoforms of the sodium channel and with other ion channels in producing their clinical signs.  It is currently unknown whether the pyrethroids as a class have similar effects on all channels or whether modifications of different types of sodium channels would have a cumulative effect.  Nor do we have a clear understanding of effects on key downstream neuronal function e.g., nerve excitability, or how these key events interact to produce their compound specific patterns of neurotoxicity.  Without such understanding, there is no basis to make a common mechanism of toxicity finding.  Therefore, EPA is not currently following a cumulative risk approach based on a common mechanism of toxicity for the pyrethroids because the Agency has determined further study is needed regarding the assumptions of dose additivity and common mechanism(s) of toxicity to appropriately identify a group or subgroups for such an assessment.  There is ongoing research by the EPA’s Office of Research and Development and pyrethroid registrants to evaluate the differential biochemical and physiological actions of pyrethroids in mammals.  The Agency anticipates the majority of this research to be completed by 2007.

FQPA Safety Factor

The Agency   SEQ CHAPTER \h \r 1 determined that the FQPA safety factor should be 1X since there are no residual uncertainties for pre and/or post natal toxicity, and   SEQ CHAPTER \h \r 1 the dietary (food and drinking water) and non-dietary exposure assessments will not underestimate the potential exposures for infants and children.   No database uncertainty factor is needed since the toxicity database is complete.

Occupational Risk

Short-term, intermediate-term, and long-term risks to occupational handlers are below the Agency’s level of concern with baseline attire (long sleeved shirt, long pants, shoes and socks), as long as wettable powder formulations are packaged in water soluble bags, and chemical resistant gloves are worn for hand-held application methods. Although risks could not be calculated for the one granular product of cypermethrin, risks would be lower than for liquid products which is below EPA’s level of concern with baseline attire.

EPA did not assess occupational postapplication risks since no short- or intermediate-term dermal endpoints were identified and long-term dermal exposures are not expected for any of the registered use patterns.    SEQ CHAPTER \h \r 1  As per the Worker Protection Standard, a restricted-entry interval of 12 hours is required for agricultural uses.

Ecological Risk

The Agency’s Tier I screening-level (deterministic) risk assessment is focused on maximum uses of cypermethrin on registered agricultural crops only, due to the   SEQ CHAPTER \h \r 1 difficulties of modeling and quantifying urban uses.  As with several other pyrethroids, the great majority of cypermethrin use is non-agricultural.  The non-agricultural applications of cypermethrin may result in exposure to aquatic organisms following runoff and/or erosion.  The Agency recognizes the potential for aquatic toxicity from non-agricultural uses but was not able to quantify the risks due to lack of available data and acceptable models.

Aquatic Risk (fish, invertebrates)

For freshwater fish, invertebrates, and estuarine/marine fish, invertebrates, technical grade cypermethrin is very highly toxic on an acute basis.  Cypermethrin formulations are also very highly toxic, with LC50 values that are similar to those reported for technical grade cypermethrin.  LOCs for acute risk (0.5) and acute endangered species risk (0.05) are exceeded for freshwater and estuarine/marine invertebrates for all six crop scenarios considered in this assessment.  The highest acute RQs are observed for freshwater invertebrates, ranging from 49.4 to 558.3, exceeding all acute LOCs.

LOCs for chronic risk (1) are exceeded for freshwater and estuarine/marine invertebrates.  The highest chronic RQs are observed for freshwater invertebrates, ranging from 57.6 to 325.4.  All chronic RQs for freshwater fish and estuarine/marine fish are less than the chronic LOC (1).

Terrestrial Risk (birds, mammals)

  SEQ CHAPTER \h \r 1 For birds, all acute (dose-based and dietary-based) RQs are below the acute risk LOC (0.5) and the endangered species LOC (0.1) for all crop uses; chronic RQs are also below the LOC (1).  The Agency’s screening level ecological risk assessment for endangered species results in the determination that cypermethrin will have no direct acute or chronic effect on threatened and endangered birds.

For mammals, acute (dose-based) RQs are below the acute risk LOC (0.5). The acute endangered species LOC (0.1) is exceeded for 15g and 35g mammals feeding on short grass (dose-based RQs 0.1-0.2) for all crop scenarios. Mammalian chronic RQs (dose-based) range from <0.1 to 9.3 (15g mammals feeding on short grass in cotton), exceeding the chronic LOC (1) for most scenarios.

Plants

  SEQ CHAPTER \h \r 1 Toxicity data are not available for terrestrial plants; thus, risks associated with cypermethrin exposure to terrestrial plants cannot be assessed.  However, based on the cypermethrin mode of action, phytotoxicity is not expected.

Non-target Insects

  SEQ CHAPTER \h \r 1 Cypermethrin exposure can present acute toxic risk to earthworms and to beneficial non-target insects, such as honey bees. This risk concern is extended to listed insects also.

Benefits and Alternatives

Usage data are sparse and generally do not distinguish between chemicals within the class.  The recent loss of chlorpyrifos and diazinon for residential pest control has resulted in a greater reliance on pyrethrins and synthetic pyrethroids, as a class, among residential users.  Most pyrethroids have similar efficacy and cost.  In the absence of any one pyrethroid, homeowners and professional applicators would most likely simply substitute another pyrethroid insecticide.  Users might also substitute insecticides from other chemical classes (e.g. organophosphates, carbamates, and neonicotinoids) and nonchemical control techniques (e.g. sanitation or exclusion).  Given the options for substitution, economic impacts of restricting any one chemical would not likely be significant.  The impact on risk of restricting any one chemical is uncertain and might increase given the substitutes available.

Risk Management

Human health risk

  SEQ CHAPTER \h \r 1 To address the handler risks of concern, the following mitigation is required:

(1) All wettable powder products must be packaged in water soluble bags including agricultural and residential (PCO/homeowner) products. Alternatively, replacing wettable powder products with products formulated as dry flowables would also reduce risks below the Agency’s level of concern.

(2) Mixers/loaders/applicators using handheld equipment (all formulations) must wear chemical resistant gloves, in addition to baseline attire (long sleeved shirt, long pants, shoes and socks).

Ecological Risk

To address the ecological risks of concern, the following mitigation is required:

For agricultural uses:

(1) Mitigation to address spray drift, including specifying minimum allowable droplet size and buffer zones, maximum allowable wind speed and release height on product labels.

(2) Decreased application rates and increased application intervals.

(3) A constructed and maintained vegetative buffer.

For non-agricultural uses (residential, commercial and industrial), mitigation includes limiting outdoor applications to impervious surfaces (such as sidewalks and driveways) to spot or crack and crevice treatments, and adding best management practices to product labels to reduce potential runoff to drains, sewers, or water bodies from outdoor nuisance pest and termite applications.

Reregistration Eligibility

  SEQ CHAPTER \h \r 1 The Agency has determined that cypermethrin is eligible for reregistration provided that the risk mitigation measures outlined in this document are adopted and labels are amended accordingly.  In addition, where there are data gaps, data must be generated to confirm the reregistration eligibility decision documented in this RED.  EPA will continue to work with cypermethrin and other pyrethroid registrants to better characterize aquatic risk from urban uses of the pyrethroids.  More data are needed to characterize ecological risk, especially risk from urban uses. EPA will continue in registration review to ensure the periodic review of all pesticides to make sure they continue to meet current scientific and regulatory requirements, with the goal of reviewing each pesticide every fifteen years.  The pyethroids are tentatively scheduled for re-evaluation under the proposed Registration Review program in 2010.

  SEQ CHAPTER \h \r 1  Introduction

The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) was amended in 1988 to accelerate the reregistration of products with active ingredients registered prior to November 1, 1984.  The amended Act calls for the development and submission of data to support the reregistration of an active ingredient, as well as EPA review of all submitted data.  Reregistration involves a thorough review of the scientific database underlying a pesticide's registration.  The purpose of the Agency's review is to reassess the potential risks arising from the currently registered uses of the pesticide, to determine the need for additional data on health and environmental effects, and to determine whether or not the pesticide meets the "no unreasonable adverse effects" criteria of FIFRA.

On August 3, 1996, the Food Quality Protection Act of 1996 (FQPA) was signed into law.  This Act amends FIFRA to require reassessment of all tolerances in effect on the day before it was enacted.  In reassessing these tolerances, the Agency must consider, among other things, aggregate risks from non-occupational sources of pesticide exposure, whether there is increased susceptibility among infants and children, and the cumulative effects of pesticides that have a common mechanism of toxicity.  When the Agency determines that aggregate risks are not of concern and concludes that there is a reasonable certainty of no harm from aggregate exposure, the tolerances are considered reassessed.  EPA decided that, for those chemicals that have tolerances and are undergoing reregistration, tolerance reassessment will be accomplished through the reregistration process.

The Food Quality Protection Act (FQPA) requires that the Agency consider available information concerning the cumulative effects of a particular pesticide’s residues and other substances that have a common mechanism of toxicity.  The reason for consideration of other substances is due to the possibility that low-level exposures to multiple chemical substances that cause a common toxic effect by a common toxic mechanism could lead to the same adverse health effect as would a higher level of exposure to any of the substances individually. Cypermethrin is a member of the pyrethroid class of pesticides.  Although all pyrethroids alter nerve function by modifying the normal biochemistry and physiology of nerve membrane sodium channels, available data shows that there are multiple types of sodium channels and that these compounds may act on different isoforms of the sodium channel and with other ion channels in producing their clinical signs.  It is currently unknown whether the pyrethroids as a class have similar effects on all channels or whether modifications of different types of sodium channels would have a cumulative effect.  Nor do we have a clear understanding of effects on key downstream neuronal function e.g., nerve excitability, or how these key events interact to produce their compound specific patterns of neurotoxicity.  Without such understanding, there is no basis to make a common mechanism of toxicity finding.  Therefore, EPA is not currently following a cumulative risk approach based on a common mechanism of toxicity for the pyrethroids because the Agency has determined further study is needed regarding the assumptions of dose additivity and common mechanism(s) of toxicity to appropriately identify a group or subgroups for such an assessment.  There is ongoing research by the EPA’s Office of Research and Development and pyrethroid registrants to evaluate the differential biochemical and physiological actions of pyrethroids in mammals.  The Agency anticipates the majority of this research to be completed by 2007.  When available, the Agency will consider this research and make a determination of common mechanism as a basis for assessing cumulative risk.  For information regarding EPA’s procedures for cumulating effects from substances found to have a common mechanism on EPA’s website at     HYPERLINK "http://www.epa.gov/pesticides/cumulative/."  http://www.epa.gov/pesticides/cumulative/.

The Agency made its reregistration eligibility determination based on the required data, the current guidelines for conducting acceptable studies to generate such data, and published scientific literature.  The Agency has found that currently registered uses of cypermethrin are eligible for reregistration provided the mitigation and labeling outlined in the RED are implemented.  The document consists of six sections:  Section I, the introduction, contains the regulatory framework for reregistration/tolerance reassessment; Section II provides an overview of the chemical, including a profile of its use and usage; Section III gives an overview of the human health and environmental effects risk assessments; Section IV presents the Agency’s reregistration eligibility, tolerance reassessment, and risk management decisions; Section V summarizes label changes necessary to implement the risk mitigation measures outlined in Section IV; and Section VI includes the appendices, related supporting documents and Data Call-In (DCI) information.  The revised risk assessment documents and related addenda are not included in this document, but are available on the Agency’s web page   HYPERLINK "http://www.epa.gov/pesticides"  http://www.epa.gov/pesticides , and in the Public Docket at   HYPERLINK "http://www.regulations.gov"  www.regulations.gov  under docket number EPA-HQ-OPP-2005-0293.

Chemical Overview

Regulatory History

Cypermethrin was first conditionally registered in 1984 by FMC Corporation, who also subsequently registered an isomer enriched zeta-cypermethrin in 1992. Current technical registrants include FMC, Syngenta, United Phosphorus International, and Valent BioSciences.  Data for the two active ingredients is considered interchangeable. Since zeta-cypermethrin was registered after 1984, only cypermethrin is subject to reregistration.  Cypermethrin is on reregistration List B; thus no Registration Standard was completed.  Data Call-ins (DCIs) for cypermethrin were issued in 1991 for basic toxicology and residue chemistry data, and in 1995 for handler exposure and worker re-entry data.

  SEQ CHAPTER \h \r 1 Cypermethrin is a synthetic pyrethroid insecticide. On June 14, 1984, the Agency conditionally registered a technical grade product and two end-use formulations each to ICI (now known as Syngenta Crop Protection) and FMC for use on cotton during the 1984 growing season. The original conditional registration for cypermethrin was subsequently renewed on January 9, 1985, and September 27, 1985.  A conditional registration for cypermethrin use on pecans was issued on April 24, 1986. The conditional registration for use on lettuce (head) was issued on March 15, 1988.

Cypermethrin is one of nine synthetic pyrethroids registered on cotton, represented by the Pyrethroid Working Group (PWG), that are considered to be conditionally registered pending the development and review of data related to aquatic toxicity.  EPA will make every effort to coordinate the implementation of its reregistration eligibility decision provisions and labeling for cypermethrin with the ongoing efforts of the PWG.

Due to the conditional status of the registration, tolerances were established for cypermethrin on a temporary basis on cottonseed, pecans, lettuce, meat, fat, and meat byproducts of hogs, horses, cattle, goats, sheep, and milk to cover residues expected to be present from use during the period of conditional registration.  On July 31, 1996, tolerances were established for brassica (head and stem) and brassica (leafy).  The conditional registrations for all cypermethrin uses were extended several times to November 15, 1993, November 15, 1994, November 15, 1995, November 15, 1996 and November 15, 1997.  At the time of FQPA, cypermethrin's tolerances had expiration dates of 11/15/97.  Agency policy was such that no temporary or time-limited tolerances were to be included among the official baseline number of tolerances which the Agency had to reassess.  These tolerances were considered revoked with an expiration date and were expected not to need tolerance reassessment, nor need to be included in the tolerance reassessment baseline count.

On November 26, 1997, permanent tolerances were established for brassica (head and stem), brassica (leafy), cattle (fat), cattle (mbyp), cattle (meat), cottonseed, goats (fat), goats (mbyp), goats (meat), hogs (fat), hogs (mbyp), hogs (meat), horses (fat), horses (mbyp), horses (meat), lettuce (head), milk, onions (bulb), pecans, sheep (fat), sheep (mbyp), and sheep (meat).  Such reassessments were not countable against the Agency's baseline number since they had not been included within the Agency's original tolerance reassessment baseline.  Upon cypermethrin RED signature, no tolerance reassessments will be counted against the Agency's baseline number, nor were any previously counted.

Chemical Identification

Cypermethrin has the following structure:

Physical/Chemical Properties  tc "Physical/Chemical Properties " \l 2

Empirical Formula:	C22H19Cl2 NO3

Molecular Weight:	416.3

CAS Registry No.:	52315-07-8

PC Code:		109702

Melting Point: 	60-80 degree C

Boiling Point: 		216 degree C

Density: 		1.204 g/mL at 25C

Vapor Pressure: 	3.1E-9 mm Hg at 20 degree C

Water Solubility: 	7.6 ppb at 25 degree C

Log P (octanol-water): 6.60

Cypermethrin is a combination of 8 stereoisomers with percentage compositions ranging from 11-14%, and very low volatility and water solubility.    SEQ CHAPTER \h \r 1 Zeta-cypermethrin is an enriched enantiomer of cypermethrin consisting of the 4 stereo isomers with an “S” configuration at the cyano bearing carbon at 24% each, and 4 insecticidally less active stereo isomers at a concentration of 1% each.  Since the analytical method does not distinguish cypermethrin from zeta-cypermethrin, and the toxicological endpoints are the same, the Agency’s human health risk assessment and environmental fate assessment considered both cypermethrin and zeta-cypermethrin.

Use Profiles

Type of Pesticide:		  SEQ CHAPTER \h \r 1 Insecticide

Summary of Use:	  SEQ CHAPTER \h \r 1 Cypermethrin   SEQ CHAPTER \h \r 1 is registered for agricultural use as a foliar application on food and feed crops including cotton, pecans, peanuts, broccoli and other Brassicas, and sweet corn.  Cypermethrin can be applied to livestock in eartags, and to horses.  Cypermethrin is also registered for use on industrial, commercial, and residential sites.  It is registered for outdoor use as a soil residual termiticide and to control insect pests such as ants in and on structures, impervious surfaces (in perimeter and crack and crevice treatments) and lawns.  Cypermethrin can also be applied indoors to control ants, cockroaches, fleas, and other insects.

Target Organisms:		Cypermethrin is registered for control of a wide range of pests.

Mode of Action:		  SEQ CHAPTER \h \r 1 It is likely that the toxic action of pyrethroids is primarily due to their blocking action on some aspect of the synaptic function of the nerve axon.

Tolerances:			  SEQ CHAPTER \h \r 1 There are 23 cypermethrin tolerances established under 40 CFR §180.418(a)(1) for pecans, bulb onions, cottonseed, head and stem brassica, green onions, head lettuce, leafy brassica and for the milk, fat, meat, and meat byproducts of cattle, goats, hogs, horses, and sheep.

Use Classification:		Agricultural products are restricted use.  Residential, commercial, and industrial products are general use (can be purchased and applied by professional applicators or by residential applicators).

Formulation Types:	  SEQ CHAPTER \h \r 1  	Cypermethrin is formulated as an emulsifiable concentrate (EC), a soluble concentrate/liquid (SC/L), and a wettable powder (WP).  Cypermethrin is compatible with a number of insecticides and fungicides, and has been formulated in products with two or more active ingredients.

Application Methods: 		  SEQ CHAPTER \h \r 1 Applications to agricultural crops can be made with aircraft, chemigation, groundboom, and air blast equipment.  Applications at industrial, commercial, and residential sites can be made using handheld equipment such as low-pressure handwand sprayers, backpack sprayers, hose-end sprayers, handgun sprayers, paintbrushes, and termiticide injectors, in addition to ready-to-use (RTU) aerosol cans, indoor foggers, pump-trigger sprayers, impregnated wipes and eartags.

Application Rates:   		The currently labeled maximum application rates for agricultural uses range from 0.4 lbs. a.i./acre to 3.4 lbs. a.i./acre.  The minimum retreatment intervals range from 3-7 days and the pre-harvest intervals (PHIs) range from 1 to 14 days. The maximum application rate for non-agricultural uses is 0.44 lbs ai/acre, for applications to lawns and turf.

Application Timing: 		Cypermethrin agricultural products can be applied at various stages of crop development.

Usage of Cypermethrin:  	Total cypermethrin use is approximately 1.0 million pounds of active ingredient (a.i.) per year.  In agriculture, it is used mainly on cotton (110,000 pounds a.i.) on about 13% of planted acres.  Minor use is also found in several other crops including pecans (6,000 pounds a.i.), peanuts, broccoli and sweet corn (1 to 2 thousand pounds a.i each).  Treatment of cattle and other livestock accounts for approximately 1,000 pounds a.i. per year.

The great majority of cypermethrin use occurs in non-agricultural sites.  Indoor pest control (mainly for ants, cockroaches, and fleas) accounts for about 110,000 pounds a.i., while outdoor use for subterranean termites and other insect pests accounts for nearly 750,000 pounds a.i. Of the non-agricultural use, approximately 300,000 pounds a.i. are applied by residential applicators, and 550,000 pounds a.i. by professional applicators.

Summary of Cypermethrin Risk Assessments

  SEQ CHAPTER \h \r 1 The purpose of this section is to highlight the key features and findings of the risk assessments in order to help the reader better understand the risk management decisions reached by the Agency.  While the risk assessments and related addenda are not included in this document, they are available in the OPP Public Docket  http://www.regulations.gov.

Human Health Risk Assessment

The following is a summary of EPA’s human health findings and conclusions for cypermethrin as presented fully in the document, “  SEQ CHAPTER \h \r 1 Cypermethrin:    SEQ CHAPTER \h \r 1 Phase 4 HED Risk Assessment for the Reregistration Eligibility Decision (RED).  PC Code 109702; DP Barcode D293416.  Dated   SEQ CHAPTER \h \r 1 06-APR-2006.

Toxicity

Technical grade cypermethrin has moderate acute toxicity via the dermal and inhalation routes (Category III & IV), and is not a skin sensitizer.  It is more toxic via the oral route (Category II).

  SEQ CHAPTER \h \r 1 Table 1:  Acute Toxicity Profile

Guideline No.	Study Type	MRID	Results	Toxicity Category

  SEQ CHAPTER \h \r 1 870.1000	  SEQ CHAPTER \h \r 1 Acute Oral - rat	  SEQ CHAPTER \h \r 1 00056800	  SEQ CHAPTER \h \r 1 LD50 (M): 247 mg/kg (F): 309 mg/kg females	II

870.1100	  SEQ CHAPTER \h \r 1 Acute Dermal

Rat

Rabbit	  SEQ CHAPTER \h \r 1 00056800

00056800	  SEQ CHAPTER \h \r 1 LD50 > 4920 mg/kg/day.

 (not calculated but higher than )

LC50:  2.5 (1.6-3.4) mg/L.  	IV

870.2400	  SEQ CHAPTER \h \r 1 Primary Eye Irritation	  SEQ CHAPTER \h \r 1 00056800	  SEQ CHAPTER \h \r 1 Slight redness of conjunctivae, chemosis & discharge. Persisted to day 7.	III

870.2500	  SEQ CHAPTER \h \r 1 Primary Skin Irritation	  SEQ CHAPTER \h \r 1 00056800	  SEQ CHAPTER \h \r 1 Slight to mild erythema on intact & abraded skin. Reversed by 48 hours. Primary Irritation Index: 0.71	IV

870.2600	  SEQ CHAPTER \h \r 1 Dermal Sensitization	  SEQ CHAPTER \h \r 1 00056800  40377701	  SEQ CHAPTER \h \r 1 Not a sensitizer in Buehler assay.  Moderate sensitizer in  Magnusson Kligman Maximization method.   N/A

  SEQ CHAPTER \h \r 1 The toxicology database for cypermethrin is complete and there are no data gaps.  The scientific quality is relatively high and the toxicity profile of cypermethrin can be characterized for all effects, including potential developmental, reproductive and neurotoxic effects.  The data provided no indication of increased susceptibility of rats or rabbits to in utero and/or postnatal exposure.

Developmental and Reproductive Toxicity

Cypermethrin is not a developmental or reproductive toxicant.    SEQ CHAPTER \h \r 1 In prenatal developmental toxicity studies in rats and rabbits, there was no evidence of developmental toxicity at the highest dose tested.  In multi-generation reproduction studies in rats, offspring toxicity was observed at the same treatment level which resulted in parental systemic toxicity.  There did not appear to be any increase in the severity of toxicity for the pups.

Neurotoxicity

  SEQ CHAPTER \h \r 1 Cypermethrin is a known neurotoxicant.  It is a member of the pyrethroid class of insecticides, which are known to induce clinical signs of neurotoxicity in mammals, but do not generally induce neuropathologic lesions.  For cypermethrin, neuromuscular effects (i.e. gait abnormalities, tremors, reduced motor activity, changes in FOB parameters and convulsions) occurred across species, sexes and routes of administration.  These clinical signs occurred following an acute exposure and appeared to be transient in nature. Effects occurred mainly in oral studies in the dog and the rat, but similar signs were also observed in an inhalation study.  Effects were not observed in dermal studies in either rats (zeta-cypermethrin) or rabbits (cypermethrin: nonabraded animals; abraded animals did exhibit decreases in activity).

Toxicological Endpoints

	Table 2 contains endpoints selected for the dietary and residential assessments.

  SEQ CHAPTER \h \r 1

Table 2:  Summary of Toxicological Doses and Endpoints for Use in Human Risk Assessments

Exposure

Scenario	Dose Used in Risk Assessment, UF 	FQPA SF and Level of Concern for Risk Assessment	Study and Toxicological Effects

Acute Dietary

general population including infants and children	NOAEL = 10 mg/kg/day

UF = 100

Acute RfD = 0.1 mg/kg/day

	FQPA SF = 1

aPAD = acute RfD

              FQPA SF

= 0.1 mg/kg/day	MRID 44962201: Acute neurotoxicity study in the rat with zeta-cypermethrin.  LOAEL = 50 mg/kg/day based on clinical signs of neurotoxicity and changes in the FOB.

Chronic Dietary

all populations	NOAEL= 6 mg/kg/day

UF = 100

Chronic RfD = 0.06 mg/kg/day	FQPA SF = 1

cPAD =

chronic RfD

 FQPA SF

= 0.06 mg/kg/day	MRID 44536801: Chronic feeding study in the dog.  LOAEL = 20.4 mg/kg/day based on clinical signs of neurotoxicity and mortality in males, and 18.1 mg/kg/day based on decreased body weights and body weight gains in females.

Short-Term Incidental Oral (1 to 30 days)	NOAEL=

10 mg/kg/day	Residential LOC for MOE = 100

Occupational LOC for MOE = N/A	MRID 44962201: Acute neurotoxicity study in the rat with zeta-cypermethrin.  LOAEL = 50 mg/kg/day based on  clinical signs of neurotoxicity and changes in the FOB

Intermediate-Term

Incidental Oral (1 - 6 months)	NOAEL= 5.0 mg/kg/day	Residential LOC for MOE = 100

Occupational LOC for MOE = N/A	MRID 44962202: Subchronic neurotoxicity study in the rat with zeta-cypermethrin.  LOAEL = 26.3 mg/kg/day based on decreased motor activity, increased landing foot splay, and decreased body weights, body weight gains, and food consumption

Short- and Intermediate-Term Dermal (1 day to 6 months	None	Residential LOC for MOE = N/A

Occupational LOC for MOE = N/A 	MRID 45010401: No systemic effects in 21-day dermal study with zeta-cypermethrin up to 1000 mg/kg/day and no developmental concern.  No hazard identified to support quantification of risk.

Long-Term Dermal (> 6 months)	Oral NOAEL=  0.6 mg/kg/day

(dermal absorption factor = 2.5%)	Occupational LOC for MOE = 100	MRID 44536801: Chronic feeding study in the dog.  LOAEL = 20.4 mg/kg/day based on clinical signs of neurotoxicity and mortality in males, and 18.1 mg/kg/day based on decreased body weights and body weight gains in females.

Short- and Intermediate-Term Inhalation (1 day to 6 months)	Inhalation NOAEL= 0.01 mg a.i./L/day (2.7 mg/kg/day)	Residential LOC for MOE =

100

Occupational LOC for MOE = 100	MRID 43507101: 21-day inhalation study in the rat.  LOAEL = 0.05 mg/L/day (13.5 mg/kg/day) based on decrease in body weight and salivation.

Long-Term Inhalation (> 6 months)	Inhalation NOAEL= 0.01 mg a.i./L (2.7 mg/kg/day)	Occupational LOC for MOE = 300 for the lack of long-term study.  Route-to-route estimation would result in less protective endpoint.	MRID 43507101: 21-day inhalation study in the rat.  LOAEL = 0.05 mg/L/day (13.5 mg/kg/day) based on decrease in body weight and salivation.

Cancer (oral, dermal, inhalation)	Classification: Category C (possible human carcinogen).  No quantification required.

UF = uncertainty factor, FQPA SF = FQPA safety factor, NOAEL = no observed adverse effect level, LOAEL = lowest observed adverse effect level, PAD = population adjusted dose (a = acute, c= chronic), RfD = reference dose, MOE = margin of exposure, LOC = level of concern, N/A = not applicable.

FQPA Safety Factor

During the Agency’s phase 3 reregistration process, an FQPA safety factor of 10x was retained due to database uncertainty (the lack of DNT study).  The DNT study has now been submitted, reviewed, and found to be acceptable. The Agency has   SEQ CHAPTER \h \r 1 determined that the FQPA safety factor should be reduced to 1X, since there are no residual uncertainties for pre- and/or post-natal toxicity.  In addition, EPA has concluded that there is no need to change any previously-selected endpoints based on the submitted DNT, and that and   SEQ CHAPTER \h \r 1 the dietary (food and drinking water) and non-dietary exposure assessments are protective of potential exposures to infants and children.

Dermal Absorption

  SEQ CHAPTER \h \r 1 A dermal absorption value of 2.5% has been estimated by comparing the maternal LOAEL of 25 mg/kg/day from the developmental study in the rat and the NOAEL (highest dose tested) of 1000 mg/kg/day from the 21-day dermal study in the rat (both conducted with zeta-cypermethrin).  Since there was no common endpoint because no systemic effects were observed in the 21-day dermal study in the rat, this is considered to be a worst-case estimate.

Dietary Exposure

Acute Dietary Exposure (food only)

  SEQ CHAPTER \h \r 1    SEQ CHAPTER \h \r 1 Zeta-cypermethrin is an S-enantiomer enriched formulation of cypermethrin.  Since the analytical method does not distinguish cypermethrin from zeta-cypermethrin, and the toxicological endpoints are the same, the dietary and non-dietary (residential) aggregate risk assessment included potential exposures from both chemicals.    SEQ CHAPTER \h \r 1 The residue of concern for tolerance enforcement and risk assessment is the parent compound (cypermethrin) only.    SEQ CHAPTER \h \r 1 EPA performed a refined (probabilistic) acute dietary assessment using PDP data, percent crop treated information, and processing factors where appropriate.  The assessment was conducted using the Dietary Exposure Evaluation Model software with the Food Commodity Intake Database (DEEM-FCID™, Version 1.3), which incorporates consumption data from USDA’s Continuing Surveys of Food Intakes by Individuals (CSFII), 1994-1996 and 1998.

Dietary risk assessment incorporates both exposure to and toxicity of a given pesticide.  Dietary risk is expressed as a percentage of a level of concern.  The level of concern is the dose predicted to result in no unreasonable adverse health effects to any human population subgroup, including sensitive members of such population subgroups.  This level of concern is referred to as the population adjusted dose (PAD), which reflects the reference dose (RfD), either acute or chronic, adjusted to account for the FQPA safety factor.

Estimated risks that are less than 100% of the PAD are below EPA’s level of concern.  The acute PAD (aPAD) is the highest predicted dose to which a person could be exposed on any given day with no adverse health effects expected.  For cypermethrin, the   SEQ CHAPTER \h \r 1 acute risk estimates are below the Agency’s level of concern (100% of the aPAD) for the general U.S. population and all population subgroups.  The most highly exposed population subgroup was children 1-2 years old at 6.1% of the aPAD at the 99.9th percentile of exposure.

Chronic Dietary Exposure (food only)

  SEQ CHAPTER \h \r 1

onducted using DEEM-FCID™, Version 1.3.  The chronic PAD (cPAD) is the highest predicted dose to which a person could be exposed over the course of a lifetime with no adverse health effects expected.  Chronic risk estimates for cypermethrin are below the Agency’s level of concern (100% of the cPAD) for the general U.S. population and all population subgroups. The most highly exposed population subgroup was children 1-2 years old at 0.2% of the cPAD.

  SEQ CHAPTER \h \r 1   SEQ CHAPTER \h \r 1

Drinking Water Exposure

(For a complete discussion, see the “  SEQ CHAPTER \h \r 1 Tier II Estimated Environmental Concentrations of Cypermethrin for the Use in the Human Health Risk Assessment” dated 05/02/2005, and the “  SEQ CHAPTER \h \r 1 Water Exposure/Risk, section 4.3 of the HED Chapter.)

  SEQ CHAPTER \h \r 1 Based on the available data, cypermethrin/zeta-cypermethrin is a moderately persistent chemical that primarily degrades by photolysis in water and biodegradation.  Cypermethrin is hydrologically stable at neutral pH.    SEQ CHAPTER \h \r 1 Cypermethrin is more light stable than the first or second generation pyrethroids like allethrin and resmethrin, but still undergoes photolysis in water, with half-lives of about a month or more in distilled water.  The rate of photolysis appears to be enhanced in natural waters (which contain photosensitizing agents like humic and fulvic acids), where it degrades with half-lives of a few days.  It binds tightly to soil particles and is not likely to move to groundwater.  The Agency has determined that the residue of toxicological concern to be included in drinking water assessment is the parent compound only.

The Estimated Drinking Water Concentrations (EDWCs)ervoir, cotton, not brassicas?] te risks from food and drinking water  for cypermethrin were estimated   SEQ CHAPTER \h \r 1 using PRZM/EXAMS, based on modeling six aerial applications to cotton in North Carolina at the maximum application rate of 0.1 lbs a.i./A (for a yearly maximum of 0.6 lb a.i./A).   SEQ CHAPTER \h \r 1 According to the label, the maximum application rate is 0.6 lb a.i./A per season, so for certain crops like lettuce which have several growing seasons in one year, exposures could be higher.  The exposure scenarios modeled assumed only one season per year.  The estimated acute drinking water concentration in surface water is 1.04 ppb, and the estimated chronic drinking water concentration in surface water is 0.013 ppb (this value represents the mean over a 30-year period).  Various other scenarios were also assessed (CA, MS and TX cotton, CA onion, and CA lettuce), but they consistently yielded lower EDWCs. The SCI-GROW model generated an EDWC for groundwater based on a maximum application rate for cypermethrin of six applications of 0.1 lbs a.i./A (this rate is representative of both cotton and lettuce). The groundwater EDWC for both acute and chronic exposures is 0.0036 ppb.

Residential Exposure and Risk

(For a complete discussion see, “  SEQ CHAPTER \h \r 1   SEQ CHAPTER \h \r 1 Cypermethrin and Zeta-Cypermethrin: Revised Occupational and Residential Exposure Assessment for the Reregistration Eligibility Decision Document”, dated April 5  SEQ CHAPTER \h \r 1 , 2006, DP barcode   SEQ CHAPTER \h \r 1 D293417).

The general public can be exposed to cypermethrin when applying the pesticide for indoor and outdoor residential pest control, or subsequent to applications made by residential applicators or professional applicators.  Non-cancer risk estimates are expressed as a margin of exposure (MOE) which is a ratio of the dose from a toxicological study selected for risk assessment, typically a NOAEL, to the predicted exposure.  Estimated MOEs are compared to a level of concern which reflects the dose selected for risk assessment and uncertainty factors (UFs) applied to that dose.  The standard UF is 100x which includes 10x for interspecies extrapolation (to account for differences between laboratory animals and humans) and 10x for intraspecies variation (to account for differences between humans).  Additional uncertainty or safety factors may also be applied.  In the case of cypermethrin, EPA’s level of concern is an MOE of 100.

Residential Handler Risk

No short-term dermal exposures or risks were assessed for cypermethrin, since no dermal endpoints of concern were identified.  EPA does not anticipate that residential handlers would have intermediate- or long-term exposures to cypermethrin or zeta-cypermethrin.  Therefore, no intermediate- or long-term risks were assessed.

EPA did assess short-term inhalation exposures and risks to residential handlers, for the following scenarios:

Mixing/Loading/Applying Liquid concentrates with Low Pressure Handwand

Mixing/Loading/Applying Liquid concentrates with Wipes

Applying Ready to Use Formulations with a Pump Sprayer (PHED aerosol can data)

Applying  Ready to Use Formulations with Aerosol Cans

Applying  Ready to Use Formulations with Fogger

Applying  Ready to Use Formulations with Wipes

Residential inhalation risks are below EPA’s level of concern (i.e., MOE > 100) for all non-occupational handler scenarios. All MOEs were greater than 16,000 which is below the Agency’s level of concern.

  SEQ CHAPTER \h \r 1 A granular product was registered on February 23, 2006 (EPA registration # 28293-367).  This product is for application to fire ant mounds on lawns and outside of homes.  Similar products are registered for liquid zeta-cypermethrin and for liquid and wettable powder cypermethrin formulations.  Due to lack of formulation-specific exposure data, no quantitative risk assessment could be conducted for the cypermethrin granular formulation.  However, the Agency believes that the risk to residential handlers from exposure to this product will not exceed that for liquid products, which is below the EPA’s level of concern.

Residential Post-application Risk

on-dietary post-application exposure to adults was assessed via the inhalation route only. Exposure to toddlers was assessed via the inhalation route, and via incidental oral exposure.  All of these exposures are considered short term.  Although cypermethrin can be used indoor as termiticide use, long term exposure due to inhalation is considered negligible, since the vapor pressure for cypermethrin is extremely low.  In general, post-application inhalation risks following outdoor applications are considered negligible as well.

Post-application inhalation risks following indoor fogger applications were assessed using time-weighted averages from a cyfluthrin room fogger air monitoring study.  Post-application inhalation risks following indoor aerosol spray applications to carpets were assessed using air concentration estimates from the crack and crevice subset of PHED, and using a House Model to estimate an emission rate.

Inhalation risks to both adults and toddlers were below the Agency’s level of concern (i.e., MOE > 100). All indoor inhalation MOEs for toddlers and adults were greater than 71,000 which is below the Agency’s level of concern.

Post-application risks to toddlers from incidental oral ingestion were assessed using a short-term incidental oral endpoint (10 mg/kg/day).  Incidental oral exposure to toddlers was assessed for the following scenarios:

Hand to mouth activity on turf

Object to mouth activity on turf

Incidental soil ingestion

Hand to mouth activity from indoor surfaces following crack & crevice treatments

Hand to mouth activity from indoor surfaces following broadcast fogger treatments

The results indicate that risks from short-term incidental oral exposures were below EPA’s level of concern for all indoor and outdoor scenarios, all MOEs were greater than 900.

Aggregate Exposure and Risk (food, drinking water, and residential)

  SEQ CHAPTER \h \r 1 In accordance with FQPA, the Agency must consider pesticide exposures and risks from all potential sources.  These usually include food, drinking water, and residential exposures.  In an aggregate assessment, exposures from relevant sources are added together and compared to quantitative estimates of hazard (e.g., a NOAEL or PAD), or the risks themselves can be aggregated.  When aggregating exposures and risks from various sources, the Agency considers both the route and duration of exposure.    SEQ CHAPTER \h \r 1 Aggregate risk assessments for cypermethrin were conducted as follows: acute and chronic aggregate assessments were conducted based on food and water exposures, and short-term aggregate assessments were conducted based on food, water, and residential exposures.  No intermediate- or long-term aggregate risk assessments were conducted because no intermediate- or long-term exposure scenarios are expected from residential uses of cypermethrin.

Acute Aggregate Risk (food and drinking water)

In order to calculate aggregate risk from exposure to cypermethrin residues in food and drinking water, EPA compared estimated cypermethrin concentrations in surface and groundwater (the EDWCs presented in section III.A.4.) with Drinking Water Levels of Comparison (DWLOCs). A DWLOC is the portion of the PAD remaining after estimated dietary (food only) exposures have been subtracted, and the remaining exposure has been converted to a concentration in ppb. This concentration value, or DWLOC, represents the potential drinking water exposure that would still fall below EPA’s level of concern.  As long as the maximum EDWCs for surface and ground water are less than the DWLOC, aggregate risks from food and drinking water exposures are below EPA’s level of concern.

In the case of cypermethrin,   SEQ CHAPTER \h \r 1 the lowest acute DWLOC of 940 ppb for children 1-2 years old is much higher than the peak EDWC of 1.04 ppb in surface water and 0.0036 ppb for ground water; therefore, acute aggregate risk estimates associated with exposure to cypermethrin residues in food and water do not exceed the Agency’s level of concern.

Short-term Aggregate Risk (food, drinking water, and residential)

Short-term aggregate exposure takes into account residential exposure plus average exposure levels to food and water (considered to be a background exposure level).  Cypermethrin   residential uses constitute short-term exposure scenarios; endpoints have been selected for short-term incidental oral and inhalation exposures, and the acceptable MOE for all short-term exposures is 100.  Since the toxicological effects through the inhalation exposure route are similar to the toxicological effects from oral exposures, the short-term aggregate risk assessment was conducted by adding the residential inhalation exposure, oral non-dietary exposure, and average food and water exposure.  The incidental oral residential exposure value selected for the aggregate analysis was based on hand to mouth activity from indoor surfaces following crack and crevice treatment, as this scenario resulted in the highest calculated exposure level, and is therefore considered protective for all other exposure scenarios.

  SEQ CHAPTER \h \r 1 Short-term aggregate risk does not exceed Agency’s level of concern for any population subgroup.  The lowest DWLOC value of 890 ppb was calculated for children 1-2 years old and this level is higher than the surface and ground water EDWCs of 0.013 and 0.0036 ppb, respectively.

Chronic Aggregate Risk (food and drinking water)

Although cypermethrin can be used indoors as a termiticide, long term inhalation exposure is not expected due to its very low vapour pressure (3.1E-9 mm Hg at 20 0C).  Therefore, the   SEQ CHAPTER \h \r 1 chronic aggregate assessment only includes food and water.  Chronic dietary estimates of exposure from food were taken from the dietary exposure model results described above.  The calculated DWLOCs for children 1-2 years old has the lowest chronic DWLOC value of 600 ppb, which is greater than both the surface water (0.013 ppb) and ground water (0.0036 ppb) EDWCs; therefore, chronic aggregate risk estimates do not exceed the Agency’s level of concern.

  SEQ CHAPTER \h \r 1 Occupational Exposure and Risk

For a complete discussion, see section 7.0 of the “  SEQ CHAPTER \h \r 1 Cypermethrin:  Phase 4 HED Risk Assessment for the Reregistration Eligibility Decision (RED).  PC Code 109702; DP Barcode D293416”, dated April 6, 2006.  Also, see “  SEQ CHAPTER \h \r 1   SEQ CHAPTER \h \r 1 Cypermethrin and Zeta-Cypermethrin: Revised Occupational and Residential Exposure Assessment for the Reregistration Eligibility Decision Document”, dated April 5  SEQ CHAPTER \h \r 1 , 2006, DP barcode   SEQ CHAPTER \h \r 1 D293417.  Although the occupational risk assessment included zeta-cypermethrin, only cypermethrin occupational assessment results are discussed here, since this reregistration decision applies only to cypermethrin products.

Workers can be exposed to cypermethrin through mixing, loading, and applying the pesticide for use on agricultural crops and livestock, and for use in indoor and outdoor industrial, commercial, and residential settings.

- - if this is not the case,

  SEQ CHAPTER \h \r 1 Occupational Handler Risk

Short- and intermediate-term dermal risks were not assessed for occupational handlers, since no short- or intermediate-term dermal endpoints were identified.  Short and intermediate-term inhalation risks to handlers when mixing, loading, and applying cypermethrin products were assessed for the following agricultural and non-agricultural scenarios:

Mixing and loading liquid and wettable powder formulations to support aerial, chemigation, groundboom, and airblast applications to agricultural crops

Applying sprays with aerial, groundboom, or airblast equipment to agricultural crops

Flagging to support aerial applications

Mixing, loading, and applying liquid formulations using a low pressure handwand sprayer, a paint brush, a low pressure/high volume turf/handgun sprayer, or a termiticide injector

Mixing, loading, and applying wettable powder formulations using a low pressure handwand sprayer, a paint brush, or a low pressure/high volume turf/handgun sprayer

Mixing, loading, and applying wettable powder formulations packaged in water soluble bags using a low pressure/high volume turf/handgun sprayer

Applying Ready-to-Use eartags, trigger pump sprayers, wipes, aerosol cans, or foggers

When data were available to assess risks, short- and intermediate-term inhalation risks to occupational handlers are below the Agency’s level of concern (i.e., MOE >100) at baseline (long sleeved shirt, long pants, shoes and socks) for all formulations except the wettable powder. For   SEQ CHAPTER \h \r 1 handlers mixing and loading to support aerial applications to cotton (a high acreage crop), sodfarms, and agricultural uncultivated areas, fencerows and hedgerows, MOEs at baseline range from 4 to 37.  The addition of engineering controls (packaging wettable powders in water soluble bags) reduces the risks to below EPA’s level of concern for all scenarios.  EPA has insufficient data to assess exposures to pilots in open cockpits. Inhalation risks to pilots in enclosed cockpits were below EPA’s level of concern for all agricultural crop scenarios.  No data are available to assess inhalation risks during the application of impregnated eartags; however, the risks are expected to be well below the inhalation risks (MOE=15,000) from applications using a ready-to-use aerosol can (considered to represent a worst case exposure scenario).

A few occupational handler exposure scenarios may be considered long-term, including applications to residential, commercial, and industrial turf by commercial lawn care operators and applications in and around residential, commercial, and industrial premises by commercial pest control operators.  Since the toxicological endpoints of concern for long-term exposures are based on similar adverse effects, long-term dermal and inhalation risks must be combined  for occupational scenarios where long-term exposures are anticipated. The target MOEs for long-term occupational workers are 100 for dermal risk and 300 inhalation risk.  Since these MOEs differ, an aggregate risk index (ARI) was used to assess combined long-term dermal and inhalation risks to handlers.  The target ARI is 1; therefore, ARIs of less than 1 indicate potential risks of concern.

Long-term combined dermal and inhalation risks were assessed for the following scenarios:

Mixing, loading, and applying liquid and wettable powder formulations using a low pressure handwand sprayer, a paint brush, or a low pressure/high volume turf/handgun sprayer

Mixing, loading, and applying wettable powder formulations packaged in water soluble bags using a low pressure/high volume turf/handgun sprayer

Combined long-term dermal and inhalation risks are below EPA’s level of concern for all scenarios involving liquid formulations at baseline attire or with the addition of chemical-resistant gloves to baseline attire.  Combined long-term dermal and inhalation risks are below EPA’s level of concern for all scenarios involving wettable powder formulations at baseline attire or with the addition of chemical-resistant gloves to baseline attire, except mixing/loading/applying wettable powders with a low-pressure handwand sprayer. Although data were not available to estimate the risks from mixing/loading and applying wettable powders packaged in water soluble bags with a low-pressure handwand sprayer, the risks are expected to be lower than for liquid products (below EPA’s level of concern with the addition of chemical-resistant gloves to baseline attire).  A similar reduction in risk would be expected if wettable powder products were reformulated into dry flowable formulations.

b.	  SEQ CHAPTER \h \r 1 Occupational Post-application Risk

EPA did not assess occupational postapplication risks to agricultural workers following treatments to agricultural crops, since no short- or intermediate-term dermal endpoints of concern were identified and long-term dermal exposures are not expected for tasks involving any of the registered crop use patterns.

EPA did not assess occupational postapplication exposures and risks following applications of cypermethrin and zeta-cypermethrin to residential and commercial lawns, and in and around industrial, commercial, and residential premises, since no short- or intermediate-term dermal endpoints of concern were identified and long-term exposures are not expected for tasks involving any of the registered use patterns.

Human Incident Data

(For a complete discussion, see “  SEQ CHAPTER \h \r 1   SEQ CHAPTER \h \r 1 Review of Cypermethrin Incident Reports.  DP Barcode D293143, Chemical #109702”, dated 08/26/2003.)

  SEQ CHAPTER \h \r 1 Pyrethroids, like cypermethrin, have relatively low toxicity to humans. Skin and eye irritation, nausea, vomiting, coughing and difficulty breathing were the most commonly reported symptoms. As with other pyrethroids, burning or tingling sensations are often reported by applicators (World Health Organization 1989). The occurrence of moderate and more serious symptoms was generally more prevalent among those exposed to cypermethrin than those exposed to other pesticides. Reports suggest that cypermethrin can cause asthma or asthma-like symptoms in susceptible individuals. See Section IV for further discussion of incidents and mitigation.

  SEQ CHAPTER \h \r 1 Environmental Risk Assessment

More detailed information can be found in the “  SEQ CHAPTER \h \r 1 Revised EFED Risk Assessment for the Reregistration Eligibility Decision (RED) on Cypermethrin After 30-Day “Error Only” Comment Period”,   SEQ CHAPTER \h \r 1 DP Barcode: D293412, dated   SEQ CHAPTER \h \r 1 October 25, 2005 and the “Addendum to the EFED RED Chapter for Cypermethrin”, DP Barcode D293413, dated June 9, 2006.

The majority of cypermethrin use occurs in non-agricultural sites.  Non-agricultural applications of cypermethrin, such as perimeter treatments around buildings and applications to lawns, may result in exposure to aquatic organisms from surface runoff and/or erosion.  Even though cypermethrin has a strong affinity to bind to soils and surfaces, residues at concentrations toxic to aquatic organisms have been measured in streams that receive runoff from suburban developments.  A study recently conducted in an urban area of California found residues of cypermethrin and other pyrethroids in urban streams adjacent to residential areas and suggested that these areas are unlikely to be unique, particularly in dry regions where landscape irrigation can dominate seasonal flow in some water bodies.  The Agency recognizes the potential for aquatic toxicity from non-agricultural uses. However, EPA was not able to assess the risks associated with urban runoff due to limited monitoring data and lack of acceptable models.  The Agency’s future plans to assess non-agricultural uses of cypermethrin and other pyrethroids are discussed in Section IV.

The Agency’s Tier I screening-level (deterministic) risk assessment is focused on registered agricultural uses only.  A summary of the Agency’s environmental fate assessment is presented below.

Environmental Fate and Transport

For the most part,   SEQ CHAPTER \h \r 1 the environmental fate data for cypermethrin were from studies on cypermethrin; however, some studies were conducted on zeta-cypermethrin as well as other isomers.  Both cypermethrin and zeta-cypermethrin are expected to have similar fate in the environment.

  SEQ CHAPTER \h \r 1 Cypermethrin is expected to bind strongly to organic carbon and have little mobility in soil (KOC values ranged from 20,800 to 385,000 L/kg), and therefore it is not likely to leach into groundwater.    SEQ CHAPTER \h \r 1 Due to its relatively low mobility, cypermethrin is most likely to reach adjacent bodies of water via spray drift, through runoff events accompanied by soil erosion, or in runoff from outdoor impervious surfaces.  Cypermethrin is moderately persistent in the environment and degrades through a combination of biotic and abiotic mechanisms.  In soil,   SEQ CHAPTER \h \r 1 under both aerobic and anaerobic conditions, cypermethrin biodegrades relatively slowly, with half-lives on the order of about 2 months.  In contrast, degradation is enhanced in water, with aerobic and anaerobic metabolism half-lives of 9 to 17 days.  If released to surface water, cypermethrin partitions to sediment, where it may degrade more slowly.  In terrestrial field dissipation studies, cypermethrin did not appear to persist in soil, where the major routes of degradation are photolysis and aerobic biodegradation. Degradation of cypermethrin through photolysis appears to be enhanced in natural waters which contain humic and fulvic acids.   SEQ CHAPTER \h \r 1 However, field studies conducted on rice (with zeta-cypermethrin) show high persistence in aquatic sediments.  If cypermethrin is applied repeatedly, it is possible that the chemical can accumulate in the sediment in ever larger amounts, with slow biodegradation. Cypermethrin bioaccumulates moderately (488x) in fish.

Ecological Risk

  SEQ CHAPTER \h \r 1 The Agency’s ecological risk assessment compares toxicity endpoints from ecological toxicity studies to estimated environmental concentrations (EECs) based on environmental fate characteristics and pesticide use data.  To evaluate the potential risk to non-target organisms from the use of cypermethrin products, the Agency calculates a Risk Quotient (RQ), which is the ratio of the EEC to the most sensitive toxicity endpoint values, such as the median lethal dose (LD50) or the median lethal concentration (LC50).  These RQ values are then compared to the Agency’s levels of concern (LOCs), which indicate whether a pesticide, when used as directed, has the potential to cause adverse effects to non-target organisms.  When the RQ exceeds the LOC for a particular category, the Agency presumes a risk of concern.  These risks of concern may be addressed by further refinements of the risk assessment or mitigation measures.  Use, toxicity, fate, and exposure are considered when characterizing the risk, as well as the levels of uncertainty in the assessment.  EPA further characterizes ecological risk based on any reported incidents to non-target terrestrial or aquatic organisms in the field (e.g., fish or bird kills).

  SEQ CHAPTER \h \r 1 Table 3.  EPA’s Levels of Concern and Associated Risk Presumptions

Risk Presumption	LOC

Terrestrial Animals	LOC

Aquatic Animals	LOC Plants

Acute Risk - there is potential for acute risk	0.5	0.5	1

Acute Endangered Species - endangered species may be adversely affected 0.1	0.05	1

Chronic Risk - there is potential for chronic risk	1	1	N/A

Risk to Aquatic Organisms

Fish and Invertebrate Toxicity

The   SEQ CHAPTER \h \r 1 results of acute toxicity studies in fish, invertebrates, and benthic organisms show that technical grade cypermethrin is very highly toxic on an acute basis.  For freshwater fish and estuarine/marine fish, the lowest toxicity values reported were an LC50 of 0.39 µg a.i./L  (rainbow trout), and an LC50 of 0.95 µg a.i./L (sheepshead minnow), indicating that these organisms all have a similar susceptibility to cypermethrin. For freshwater invertebrates the lowest toxicity values reported were an LC50 of 0.0036 µg a.i./L (waterflea) and for estuarine/marine invertebrates an LC50 of 0.00475 µg ai/L (mysid shrimp), approximately 100 times lower than the toxicity values reported for fish. These results indicate that freshwater and estuarine/marine invertebrates are substantially more sensitive than other types of aquatic organisms to cypermethrin toxicity, and that they are expected to be at greatest risk for acute effects (death).

  SEQ CHAPTER \h \r 1 The available experimental LC50 value for benthic amphipods is expressed in terms of sediment concentration of cypermethrin (LC50 = 3.6 µg a.i./kg sediment).  To assess risk to benthic organisms in terms of pore water, a surrogate benthic organism LC50 value for pore water (0.00257 µg a.i./L pore water) was derived using the sediment LC50 value and the average Koc value (141,700) for cypermethrin.  In oysters, cypermethrin is categorized as highly toxic (370 µg a.i./L).

g of active ingredient/L) for Aquatic Organisms " \f D  .

Exposure Scenario	Species 	Exposure Duration	Toxicity Reference Value (µg a.i./L)	Effects	Reference

Freshwater Fish	rainbow trout	96 hours	LC50 = 0.39 µg a.i./L	Morbidity MRID 44546027

Freshwater Invertebrates	amiphod	48 hours	LC50 = 0.0036 µg a.i./L Morbidity	MRID 44423501

Benthic Organisms	amphipod	10 days	sediment value (experimental data):

LC50 = 3.6 µg a.i./kg sediment

pore water value (derived data):

LC50 =  0.00257 µg a.i./L pore water	Morbidity and Growth	MRID 44074406

Estuarine/

Marine Fish	sheepshead minnow	96 hours	LC50 = 0.95 µg a.i./L	Morbidity MRID 90075

Estuarine/

Marine Invertebrates	mysid shrimp	96 hours   	LC50 = 0.00475 µg a.i./L Morbidity	Acc. No. 42444601

  SEQ CHAPTER \h \r 1 Chronic toxicity studies are available for freshwater fish and estuarine/marine invertebrates.  Results in freshwater fish show that neonate survival is adversely affected by cypermethrin exposure (NOAEC = 0.14 µg a.i./L). For estuarine/marine invertebrates, chronic exposure to cypermethrin produced adverse effects on reproductive (NOAEC = 0.0015 µg a.i./L) and growth parameters (NOAEC = 0.000781 µg a.i./L).

Table 5.  Cypermethrin (Technical Grade) Chronic Toxicity Reference Values for Aquatic Organisms tc "Table 12.  Cypermethrin Toxicity Reference Values (TRVs) (g of active ingredient/L) for Aquatic Organisms " \f D  .

Exposure Scenario	Species 	Exposure Duration	Toxicity Reference Value (µg a.i./L)	Effects	Reference

Freshwater Fish	fathead minnow	30 days	NOAEC = 0.14 µg a.i./L

LOAEC = 0.33 µg ai/L	Growth and morbidity	MRID 89039

Freshwater Invertebrates	No adequate data submitted; to assess chronic risk to freshwater invertebrates,  surrogate NOAEC value of  0.00059 µg a.i./L was derived based on the acute:chronic ratio method using acute and chronic data for estuarine/marine invertebrates.

Benthic Organisms	No chronic data submitted; to assess chronic risk to benthic organisms, surrogate chronic NOAEC toxicity values for sediment of  0.59 µg a.i./kg sediment  and for pore water of 0.00042 µg a.i./L pore water  were derived based on the acute:chronic ratio method using acute and chronic data for estuarine/marine invertebrates.

Estuarine/Marine Fish	No data submitted; to assess chronic risk to estuarine/marine fish, a surrogate NOAEC value of 0.34 µg a.i./L for sheepshead minnow was derived based on the acute:chronic ratio method using acute and chronic data for freshwater fish.  e

Estuarine/

Marine Invertebrates	mysid shrimp	28 days  	NOAEC = 0.000781 µg a.i./L

LOAEC = 0.00197 µg ai/L

NOAEC = 0.0015 µg ai/L

LOAEC = 0.0028 µg ai/L	Weight of females reduced

Number of offspring reduced	MRID 42725301

Fish and Invertebrate Exposure

For exposure to aquatic fish and invertebrates, EPA considers surface water only, since most aquatic organisms are not found in ground water.    SEQ CHAPTER \h \r 1 Estimated environmental concentrations (EECs) for cypermethrin calculated using the Tier II PRZM/EXAMS models and employing maximum application rates, indicate that cypermethrin preferentially partitions to the sediment.  Three crop usage scenarios, which constitute approximately 90% of cypermethrin’s total crop usage, were considered: cotton, lettuce, and pecans.  Modeling produced the highest EECs for cotton crops in North Carolina and Mississippi.    SEQ CHAPTER \h \r 1 A complete listing of EECs can be found in the EFED risk assessment, dated October 25, 2005.

  SEQ CHAPTER \h \r 1 Fish and Invertebrate Risk

  SEQ CHAPTER \h \r 1 To assess risks of cypermethrin to non-target aquatic animals (i.e., fish and invertebrates), EPA uses the peak concentration to derive RQs for acute exposure and the 21-day average concentration to derive RQs for chronic exposure.  RQs are calculated as the concentration (peak or average EEC) divided by the relevant endpoint (LC50 for acute risk, NOAEC for chronic risk).  Since results of acute toxicity studies in freshwater fish and invertebrates indicate that the major cypermethrin degradate (3-phenoxy benzoic acid) is much less toxic than the parent compound, EECs and RQs were derived only for the parent compound, not for total residue (parent plus degradates).  Acute risk quotient (RQ) values were calculated using the endpoint from the most sensitive species tested within a taxonomic group.

  SEQ CHAPTER \h \r 1 Acute RQs for aquatic organisms are summarized in Table 6. The LOC for acute risk (LOC 0.5) is exceeded for all aquatic organisms and modeled crop scenarios, except CA cotton for freshwater invertebrates and estuarine/marine fish, and CA lettuce for estuarine/marine fish. LOCs for acute endangered species risk (LOC 0.05) are exceeded for freshwater fish and invertebrates and estuarine/marine fish and invertebrates for all six crop scenarios assessed. The highest acute RQs are observed for freshwater invertebrates, ranging from 49.4 (CA cotton) to 558.3 (NC cotton), exceeding all acute LOCs.

Table 6.  Acute RQs for Freshwater Fish, Freshwater Invertebrates, Estuarine/Marine Fish and Estuarine/Marine Invertebrates Exposed to Cypermethrin. tc "Table 14.  Acute RQs for Freshwater Fish, Freshwater Invertebrates, Estuarine/Marine Fish and Estuarine/Marine Invertebrates Exposed to Cypermethrin " \f D

Crop Use

	PRZM/EXAMS Scenario	Freshwater Fish

Acute RQ	Freshwater Invertebrate

Acute RQ	Estuarine/Marine

Fish

Acute RQ	Estuarine/Marine

Invertebrate

Acute RQ

Cotton	California	0.5	49.4	0.2	37

	Mississippi	3.3	355.6	1.3	269

	North Carolina	5.2	558.3	2.1	423

	Texas	1.3	136.9	0.5	104

Pecans	Georgia	2.4	264.7	1.0	201

Lettuce (Head)	California	0.7	80.6	0.3	61

Chronic RQs for aquatic animals are summarized in Table 7.  For freshwater invertebrates, chronic RQs range from 57.6 to 325.4 and for estuarine/marine invertebrates, chronic RQs range from 44 to 246 and, exceeding the chronic LOC (1).  For freshwater fish and estuarine/marine fish, all chronic RQs are below the chronic LOC.

Table 7.  Chronic RQs for Freshwater Fish, Freshwater Invertebrates, Estuarine/Marine Fish and Estuarine/Marine Invertebrates Exposed to Cypermethrin. tc "Table 15.  Chronic RQs for Freshwater Fish, Freshwater Invertebrates, Estuarine/Marine Fish and Estuarine/Marine Invertebrates Exposed to Cypermethrin " \f D

Crop Use

	PRZM/EXAMS Scenario	Freshwater Fish

Chronic RQ	Freshwater Invertebrate

Chronic RQ	Estuarine/Marine

Fish

Chronic RQ	Estuarine/Marine

Invertebrate

Chronic RQ

Cotton	California	0.2	93.2	0.1	70

	Mississippi	0.7	318.6	0.3	241

	North Carolina	0.7	325.4	0.3	246

	Texas	0.2	101.7	0.1	77

Pecans	Georgia	0.3	145.8	0.1	110

Lettuce (Head)	California	0.1	57.6	0.1	44

Sediment Exposure - Acute and Chronic Risk  tc "b.         Sediment Exposure - Acute and Chronic Risk " \l 4

Acute and chronic RQs have been derived for exposure of benthic organisms to sediments and pore water (Table 10).  All acute and chronic RQs for benthic organisms exceed the LOCs for acute risk (LOC 0.5), acute endangered species risk (LOC 0.05) and chronic risk (LOC 1) for all modeled crop uses. There are several uncertainties regarding both acute and chronic RQs.  Due to data gaps, acute RQs for pore water and chronic RQs for sediment and pore water were derived from estimated toxicity values based on the acute sediment toxicity value.  However, there is considerable uncertainty surrounding the acute sediment toxicity value, since this value was obtained from a study using a water-sediment system that was not at equilibrium (sediment concentrations decreased throughout the exposure period).  SEQ CHAPTER \h \r 1

Table 8.  Acute and Chronic RQs for Benthic Organisms Exposed to Cypermethrin tc "Table 16.  Acute and Chronic RQs for Benthic Organisms Exposed to Cypermethrin " \f D  .

Crop Use

	PRZM/EXAMS Scenario	Sediment Acute RQ 	Pore Water Acute RQ 	Sediment

Chronic RQ 	Pore Water

Chronic RQ

Cotton	California	7	2	35	9

	Mississippi	44	11	228	57

	North Carolina	48	12	244	60

	Texas	13	3	52	13

Pecans	Georgia	26	7	123	31

Lettuce (Head)	California	8	2	47	12

iv.	  SEQ CHAPTER \h \r 1 Aquatic Plant Toxicity, Exposure and Risk

  SEQ CHAPTER \h \r 1 Toxicity data are not available for aquatic plants; thus, risks associated with cypermethrin exposure to aquatic plants could not be assessed. However, based on cypermethrin’s mode of action, cypermethrin is not expected to be phytotoxic.  In addition, the Agency is not aware of any plant incidents involving exposure to cypermethrin.

v.	Effect of Buffers on Spray Drift

The screening-level risk assessment indicates that peak EECs exceed acute levels-of-concern for all aquatic taxa considered. The ecological risk assessment includes an evaluation of the relative contribution of runoff and spray drift to the exposure simulated by PRZM/EXAMS. A hypothetical scenario was run (for use on NC cotton) in which application of cypermethrin resulted in no spray drift. The resulting EEC of 2.2 µg a.i./L, which represented transport of cypermethrin to water via runoff and erosion alone, is high enough to exceed the acute LOC for all aquatic taxa.

The effect of a 150-foot spray buffer on potential exposure from runoff and erosion cannot currently be quantified. Presumably, the mass of cypermethrin that would be applied to that portion the field within 150 feet of a water body would be less than that applied to the rest of the crop, and would decline with distance. However, the PRZM model is an edge-of-field model which cannot simulate an untreated area between the field and the receiving water body.

The expected effect of a spray buffer on exposure through spray drift can be quantified using the AgDRIFT model, which was developed using extensive field data collected by the Spray Drift Task Force. This is important because while the EEC from PRZM/EXAMS used in the screening model represents a 1-in-10-year exposure from combined runoff/erosion and spray drift, the output from AgDRIFT can be made to represent the amount of exposure from spray drift that could occur any time a pesticide is applied.

AgDRIFT modeling for cypermethrin indicates that the exposure from spray drift alone could be sufficient to exceed levels of concern for aquatic organisms, and that implementation of a spray buffer can reduce that exposure significantly. Using typical spray conditions (10 ft. release height, 10 mph wind, and a fine-to-medium droplet size distribution [DSD]), the AgDRIFT model simulates a concentration of 0.73 µg a.i./L in the standard pond from spray drift if no buffer zone is observed. Risk quotients calculated with this EEC would exceed the acute LOCs of 0.5 for freshwater and estuarine/marine fish and invertebrates.

The table below shows the effect of spray buffers on the concentration of cypermethrin that AgDRIFT simulates in the standard pond. These values reflect the typical spray conditions described above, and an application rate of 0.1 lb ai/acre:

Table 9.   tc "Table 16.  Acute and Chronic RQs for Benthic Organisms Exposed to Cypermethrin " \f D  Effect of Various Buffers on EECs

Buffer (ft)	0	50	100	150	200

Concentration (µg a.i./L)

0.73

0.44

0.31

0.24

0.20

When a buffer of 150 feet is simulated, the resulting concentration of cypermethrin in the pond resulting from drift alone is reduced by two-thirds. This is sufficient to reduce the EEC below the acute level-of-concern of 0.5 for estuarine/marine fish (RQ = 0.24 µg a.i./L/0.95 µg a.i./L = 0.25). This reduction would not reduce the risk quotients for drift alone below the acute LOC for freshwater fish (RQs of 0.61), but the reduction in exposure could lead to lower levels of mortality, and perhaps be sufficiently protective for less sensitive species. The toxicity reference values for freshwater and estuarine/marine invertebrates (LC50 = 0.0036 and 0.0048 µg a.i./L, respectively) are so low that even a two-third reduction in exposure still results in RQs far above the LOC (RQ = 67 and 50, respectively).

The use of a spray buffer would reduce exposure under conditions other than the typical conditions described above, but conditions more conducive to spray drift could result in unacceptable exposure from drift alone regardless of the buffer. For instance, if the wind speed (10 mph) and release height (10 ft) are kept the same as above, but a very fine-to-fine DSD is simulated instead of a fine-to-medium DSD, much greater exposure to cypermethrin could result.

Table 10.   tc "Table 16.  Acute and Chronic RQs for Benthic Organisms Exposed to Cypermethrin " \f D  Effect of Various Buffers Using Fine-to-Fine Droplets on EECs

Buffer (ft)	0	50	100	150	200

Concentration (µg a.i./L)

1.7

1.2

0.96

0.8

0.68

The resulting amount of spray drift would lead to more than three times the exposure at 150 feet than if the fine-to-medium DSD were used, and the resulting EECs would still exceed the LOC for all aquatic taxa.

䔀潣剬獩呒剒剒൒ግ匠充䌠䅈呐ER \h \r 1 In addition to these potential acute and chronic risks from agricultural uses, aquatic organisms may be exposed to cypermethrin from non-agricultural uses, as well.  The Agency has received and considered the results of a published study that measured pyrethroid residues in stream sediments adjacent to an urban subdivision in California. The study found toxic residue levels of cypermethrin and other pyrethroids in stream sediments that receive runoff from the subdivisions via storm drains and summer over-irrigation of landscapes and lawns (Weston, et al., 2005).  Although bifenthrin was the major pyrethroid found, cypermethrin concentrations were also of toxic significance to aquatic invertebrates. Weston’s work is significant because it documents the presence of pyrethroids in the sediments of creeks near residential areas.  Since most of the use of cypermethrin is in non-agricultural settings, urban uses pose additional risks to aquatic systems that the Agency cannot quantitatively assess at this time.  EPA currently is evaluating appropriate modeling approaches to assess risks from urban runoff (see Chapter IV for further discussion).

b.	Risk to Terrestrial Organisms

				i.	Bird and Mammal Toxicity

  SEQ CHAPTER \h \r 1 Results of acute toxicity studies on birds suggest that cypermethrin is practically non-toxic to slightly toxic to avian species (LD50 >2,000 mg a.i./kg body weight; LC50 > 2,634 mg a.i./kg diet) on an acute basis. Chronic avian studies showed no adverse effects at 50 mg a.i./kg diet (the highest dose tested), but the study was incomplete because a LOAEC was not determined

Mammalian data suggest that cypermethrin is moderately toxic (LD50 = 247 mg/kg body weight) on an acute basis.  A chronic study in rats showed adverse effects (decreased body weight and body weight gain) in adults and offspring (NOAEC = 5.0 mg a.i./kg/ body weight/day; 100 mg a.i./kg diet).

Table 11.  Cypermethrin Toxicity Reference Values for Terrestrial Organisms tc "Table 13.  Cypermethrin Toxicity Reference Values (TRVs) for Terrestrial Organisms " \f D  .

Exposure Scenario	Species 	Exposure Duration	Toxicity Reference Value

	Reference

Mammals

Acute

(Dose-based)	rat	single oral dose	LD50 (M): 247 mg/kg/ body wt	MRID 00056800

Chronic

(Dietary-based  and

Dose-based)	rat	3 generation reproduction study

	NOAEL (toxicity to parents and offspring) = 5.0 mg/kg/day

LOAEC  = (toxicity to parents and offspring) = 25 mg/kg/day	MRID 00090040

Birds

Acute

(Dose-based)	bobwhite quail	single oral dose	LD50 >2,000 mg a.i./kg body wt	MRID 44546024

Acute

(Dietary-based)	mallard duck	5-day dietary	LC50 >2,634 mg a.i./kg diet MRID 00090071

Chronic

(Dietary-based)	mallard duck and

bobwhite quail	Avian reproduction 	NOAEC >50 mg a.i./kg diet	MRID 42322902

MRID 42322901

 tc "a.     Terrestrial " \l 4

				ii.	Bird and Mammal Exposure

  SEQ CHAPTER \h \r 1 The Agency assessed exposure to terrestrial organisms by first predicting the amount of cypermethrin residues found on animal food items and then using information on typical food consumption by various species of birds and mammals to determine the amount of pesticide consumed.  The amount of residues on animal feed items is based on the Fletcher nomogram, which is a model developed by Hoerger and Kenaga (1972) and modified by Fletcher (1994), and the current maximum application rates for cypermethrin.

Estimated exposure concentrations for terrestrial receptors were determined using the standard screening-level exposure model, TREX (v.1.1), which is a simulation model that, in addition to incorporating the nomogram relationship, also includes pesticide degradation in the estimation of EECs.    SEQ CHAPTER \h \r 1 TREX considers exposure only in the area where cypermethrin is applied.  The underlying assumption is that most, if not all, of the applied pesticide will settle in the use area.  However, depending on weather conditions and type of application, spray drift of pesticides may occur, increasing the likelihood of wildlife exposure outside the use area.  Since cypermethrin is applied via spray methods, spray drift is likely to occur and in some cases could be a significant source of exposure.

Four crop usage scenarios were assessed: cotton, pecans, lettuce, and canola.  Cypermethrin maximum dose-based EECs ranged from 1.2-122 mg/kg body weight for birds, and 0.1-102 mg/kg body weight for mammals.

					iii.	Bird and Mammal Risk

  SEQ CHAPTER \h \r 1 For birds, all acute, dose-based and dietary based RQs are below the LOC for acute risk (LOC 0.5) and endangered species (LOC 0.1) for all crop uses.  However, the acute endangered species LOC (0.1) is exceeded for 15g and 35g mammals feeding on short grass (dose-based RQs 0.1-0.2) for all crop scenarios, and for 15g mammals feeding on broadleaf plants/small insects in cotton (RQ = 0.11).

Chronic, dietary-based RQs for birds are all below the LOC for chronic risk (LOC 1).  It was not possible to calculate a chronic dose-based RQ for birds because there were no acceptable dose-based toxicity values for birds available.  For mammals, chronic, dose-based RQs range from <0.1 to 9.3 (15g mammals feeding on short grass in cotton), exceeding the chronic LOC (1) for most scenarios.  The chronic dietary-based RQ (1.1) exceeded the chronic LOC (1) for mammals feeding on short grass in cotton.

					iv.	Non-target Insect Toxicity, Exposure and Risk

Results of available toxicity studies indicate that cypermethrin is highly toxic to honey bees (LD50 = 0.023 - 0.56 ug/bee) and very toxic to earthworms (LC50 = 26.09 ug/cm2) on an acute contact basis.  Thus, honey bees and other non-target terrestrial invertebrates (e.g. beneficial insects and listed insects) are expected to be at risk for acute effects (lethality).  No   SEQ CHAPTER \h \r 1 RQ values for non-target insects were derived; however, risks can be assessed qualitatively.  Cypermethrin toxicity data show that it is very highly toxic to honey bees and is considered to be highly toxic on both a contact and an oral basis.  Cypermethrin was also found to be highly toxic to honey bees exposed to foliage that had been sprayed with a cypermethrin formulation (Cymbush 3E).  In addition, cypermethrin has also been shown to be highly toxic to earthworms.  Based on these results, acute risks to non-target insects and terrestrial invertebrates are anticipated for the uses considered in this assessment.

					v.	  SEQ CHAPTER \h \r 1 Terrestrial Plants

  SEQ CHAPTER \h \r 1 As for aquatic plants, toxicity data are not available for terrestrial plants and risks could not be assessed. Cypermethrin is not expected to be phytotoxic based on its mode of action, and no incidents involving terrestrial plants have been reported to the Agency.

			c.	Ecological Incidents

  SEQ CHAPTER \h \r 1 A total of 10 aquatic incidents involving cypermethrin exposure have been reported to EPA and tracked by   SEQ CHAPTER \h \r 1 Ecological Incident Information System (EIIS).  All incidents were categorized according to the Certainty Index as follows: possible (3 reports); probable (3 reports); and highly probable (4 reports).  Although in about half of these aquatic incidents the source of cypermethrin was not reported, several fish kills were attributed to termiticide use of cypermethrin.

A total of five incidents involving terrestrial organisms (birds, goats, dog) were noted. The incident involving birds (5000 sparrows) was attributed to birds eating insects that had been killed from cypermethrin use the previous night on an eggplant crop.

  SEQ CHAPTER \h \r 1

Endangered Species Concerns

The Agency’s screening level ecological risk assessment for endangered species results in the determination that cypermethrin will have no direct acute effects on threatened and endangered birds.  However, potential indirect effects to any species dependent upon a species that experiences effects cannot be precluded from use of cypermethrin.  These findings are based solely on EPA’s screening level assessment and do not constitute “may effect” findings under the Endangered Species Act.

  SEQ CHAPTER \h \r 1 For birds, all acute RQs are below the endangered species LOC (0.1) for all crop uses.  The Agency’s acute endangered species LOC for birds was not exceeded in the screening level assessment, but one incident involving acute effects on birds was reported.

For mammals, the acute endangered species LOC (0.1) is exceeded for 15g and 35g mammals feeding on short grass (dose-based RQs 0.1-0.2) for all crop scenarios  and aquatic organisms (LOC = 0.05) were exceeded.   The maximum calculated acute RQs for all organisms resulted from modeling cypermethrin use on North Carolina cotton; the maximum screening level acute RQs which exceed acute LOCs are shown in Table 12, below.

Table 12. Maximum acute RQs in screening level assessment.

Organism	Maximum Acute RQ

Mammals	0.2

Freshwater fish	5.2

Freshwater invertebrates	558.3

Estuarine/marine fish	2.1

Estuarine/marine invertbrates	423

Benthic organisms (sediment exposure)	48

Benthic organisms (pore water exposure)	12

The Agency’s screening level assessment results in the determination that cypermethrin will have no direct chronic effects on birds (all RQs are less than the chronic LOC of 1.0).  However, the chronic LOC is exceeded for mammals, freshwater and estuarine/marine invertebrates, and benthic organisms. The maximum calculated chronic RQs for all organisms resulted from modeling cypermethrin use on North Carolina cotton; the maximum screening level chronic RQs which exceed the chronic LOC are shown in Table 13, below.

Table 13. Maximum chronic RQs in screening level assessment.

Organism	Maximum Chronic RQ

Mammals (dose-based risk)	9.3

Freshwater invertebrates	325.4

Estuarine/marine invertbrates	246

Benthic organisms (sediment exposure)	244

Benthic organisms (pore water exposure)	60

No data were submitted to evaluate the risk of cypermethrin exposure to non-target terrestrial plants.  However, the agency has determined that cypermethrin will have no effect on listed plants.  Also, no incident reports have reliably linked cypermethrin or any other synthetic pyrethroid to phytoxic effects despite the fact that pyrethroids are often applied on or near agricultural crops.

All of these findings are based solely on EPA’s screening level assessment and do not constitute “may effect” findings under the Endangered Species Act.  Rather, this assessment serves as a screen to determine the need for any species specific assessments that will evaluate whether exposure may be at levels that could cause harm to specific listed species and their critical habitat.   That assessment refines the screening-level assessment to take into account  the geographic area of pesticide use in relation to the listed species, the habits and habitat requirements of the listed species, etc.  If the Agency’s species specific assessments result in the need to modify use of the pesticide in specific geogrpahic areas, those changes to the pesticide’s registration will take through the process described in the Agency’s Federal Register Notice (54 FR 27984) regarding implementation of the Endangered Species Protection Program.

IV.	Risk Management, Reregistration, and Tolerance Reassessment Decision

A.	Determination of Reregistration Eligibility and Tolerance Reassessment

Section 4(g)(2)(A) of FIFRA calls for the Agency to determine, after submission of relevant data concerning an active ingredient, whether or not products containing the active ingredient are eligible for reregistration.  The Agency has previously identified and required the submission of the generic data to support reregistration of products containing cypermethrin and has determined that the data are sufficient to support reregistration.

The Agency has completed its assessment of the dietary, residential, occupational and ecological risk associated with the use of cypermethrin.  Based on this assessment the Agency has sufficient information to make decisions as part of the tolerance reassessment process under FFDCA and reregistration process under FIFRA, as amended by FQPA.  The Agency has determined that cypermethrin containing products are eligible for reregistration provided that label amendments are made as outlined in this RED.  Appendix A summarizes the uses of cypermethrin that are eligible for reregistration.  Appendix B identifies the generic data requirements that the Agency reviewed as part of its determination of reregistration eligibility, and lists the submitted studies that the Agency found acceptable.

Based on its evaluation of cypermethrin, the Agency has determined that cypermethrin products, unless labeled and used as specified in this document, would present risks inconsistent with FIFRA and FQPA.  Accordingly, should a registrant fail to implement any of the reregistration requirements identified in this document, the Agency may take regulatory action to address the risk concerns from the use of cypermethrin.  If all changes outlined in this document are incorporated into the product labels, then all current risks for cypermethrin will be adequately mitigated for the purposes of this determination.  Once an Endangered Species assessment is completed, further changes to these registrations may be necessary as explained under “Endangered Species Concerns” above.

B.	Public Comments and Responses

Through the Agency’s public participation process, EPA worked with stakeholders and the public to reach the regulatory decisions for cypermethrin.  EPA released its cypermethrin preliminary risk assessments for public comment on December 28, 2005, for a 60-day public comment period (Phase 3 of the public participation process).  During the public comment period, the Agency received comments from the technical registrants, the California water quality control boards, the California Stormwater Quality Association, and other stakeholders. These comments in their entirety, responses to the comments, as well as the preliminary and revised risk assessments, are available in the public docket (EPA-HQ-OPP-2005-0293) at http://www.regulations.gov.

C.	Regulatory Position

	1.	Food Quality Protection Act Findings

		a.	“Risk Cup” Determination

Even though cypermethrin tolerances are not included in EPA’s baseline tolerance reassessment counts, EPA assessed the risks associated with cypermethrin.  EPA has concluded that the tolerances for cypermethrin meet FQPA safety standards.  In reaching this determination, EPA has considered the available information on the special sensitivity of infants and children, as well as aggregate exposure from food and residential sources.

		b.	Determination of Safety to U.S. Population

The Agency has determined that the established tolerances for cypermethrin, with amendments and changes as specified in this document, meet the safety standards under the FQPA amendments to section 408(b)(2)(D) of the FFDCA, as amended by FQPA, and that there is a reasonable certainty no harm will result to the general population or any subgroup from the use of cypermethrin.  In reaching this conclusion, the Agency has considered all available information on the toxicity, use practices, and the environmental behavior of cypermethrin.  As discussed in Section III, aggregate acute, short-, intermediate-, and long-term risks from food, drinking water, and residential exposures are below the Agency’s LOC.

		c.	Determination of Safety to Infants and Children

EPA has determined that the established tolerances for cypermethrin, with amendments and changes as specified in this document, meet the safety standards under the FQPA amendments to section 408(b)(2)(C) of the FFDCA, that there is a reasonable certainty of no harm for infants and children.  The safety determination for infants and children considers factors on the toxicity, use practices and environmental behavior noted above for the general population, but also takes into account the possibility of increased dietary exposure due to the specific consumption patterns of infants and children, as well as the possibility of increased susceptibility to the toxic effects of cypermethrin residues in this population subgroup.

In determining whether or not infants and children are particularly susceptible to toxic effects from exposure to residues of cypermethrin, the Agency considered the completeness of the hazard database for developmental and reproductive effects including a developmental neurotox study, the nature of the effects observed, and other information.  The FQPA Safety Factor has been reduced to 1X, because there are no residual uncertainties for pre- and/or post-natal toxicity, exposure is not underestimated, and there is no evidence of increased susceptibility.

	2.	Endocrine Disruptor Effects

The available database provides no evidence that cypermethrin induces endocrine disruption.

EPA is required under the FFDCA, as amended by FQPA, to develop a screening program to determine whether certain substances (including all pesticide active and other ingredients) “may have an effect in humans that is similar to an effect produced by a naturally occurring estrogen, or other endocrine effects as the Administrator may designate.”  Following recommendations of its Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC), EPA determined that there was a scientific basis for including, as part of the program, the androgen and thyroid hormone systems, in addition to the estrogen hormone system.  EPA also adopted EDSTAC’s recommendation that EPA include evaluations of potential effects in wildlife.  For pesticides, EPA will use FIFRA and, to the extent that effects in wildlife may help determine whether a substance may have an effect in humans, FFDCA authority to require the wildlife evaluations.  As the science develops and resources allow, screening of additional hormone systems may be added to the Endocrine Disruptor Screening Program (EDSP).  In the available toxicity studies on cypermethrin submitted for registration purposes, there was no estrogen, androgen, and/or thyroid mediated toxicity. When the appropriate screening and/or testing protocols being considered under the EDSP have been developed, cypermethrin may be subject to additional screening and/or testing.

		3.	Cumulative Risks

Cypermethrin is a member of the pyrethroid class of pesticides.  Although all pyrethroids alter nerve function by modifying the normal biochemistry and physiology of nerve membrane sodium channels, available data shows that there are multiple types of sodium channels and that these compounds may act on different isoforms of the sodium channel and with other ion channels in producing their clinical signs.  It is currently unknown whether the pyrethroids as a class have similar effects on all channels or whether modifications of different types of sodium channels would have a cumulative effect.  Nor do we have a clear understanding of effects on key downstream neuronal function e.g., nerve excitability, or how these key events interact to produce their compound specific patterns of neurotoxicity.  Without such understanding, there is no basis to make a common mechanism of toxicity finding.  Therefore, EPA is not currently following a cumulative risk approach based on a common mechanism of toxicity for the pyrethroids because the Agency has determined further study is needed regarding the assumptions of dose additivity and common mechanism(s) of toxicity to appropriately identify a group or subgroups for such an assessment.  There is ongoing research by the EPA’s Office of Research and Development and pyrethroid registrants to evaluate the differential biochemical and physiological actions of pyrethroids in mammals.  The Agency anticipates the majority of this research to be completed by 2007.  When available, the Agency will consider this research and make a determination of common mechanism as a basis for assessing cumulative risk.  For information regarding EPA’s procedures for cumulating effects from substances found to have a common mechanism on EPA’s website at     HYPERLINK "http://www.epa.gov/pesticides/cumulative/."  http://www.epa.gov/pesticides/cumulative/ .

D.	Tolerance Reassessment Summary

  SEQ CHAPTER \h \r 1 The Codex Alimentarius Commission has established several maximum residue limits (MRLs) for cypermethrin residues in/on various plant and livestock commodities.  The Codex and U.S. tolerances are in harmony with respect to MRL/tolerance expression.  Both regulate the parent compound, cypermethrin.

Special efforts to increase harmony between recommended US tolerance levels and Codex MRLs were made for the following commodities: 1) poultry, meat (0.05 ppm instead of no tolerance), and 2) meat of cattle, goat, sheep, and horse (0.20 instead of 0.05 ppm).  The following conclusions can be made regarding efforts to harmonize the U.S. tolerances with the Codex MRLs with respect to MRL/tolerance level:  (i) compatibility between the U.S. tolerances and Codex MRLs exists for bulb onions; meat byproducts; poultry, meat; and meat of cattle, goat, sheep, and horse; and (ii) incompatibility of the U.S. tolerances and Codex MRLs remains for Brassica vegetables, cottonseed, lettuce, and milk, because of differences in good agricultural practices and determination of secondary residue levels in livestock commodities.  No questions of compatibility exist with respect to commodities where Codex MRLs have been established but U.S. tolerances do not exist, or vice versa.

  SEQ CHAPTER \h \r 1 A summary of cypermethrin tolerance reassessments is presented in Table 14.

Table 14. Tolerance Reassessment Summary for Cypermethrin.

Commodity	Current Tolerance

(ppm)	Tolerance Reassessment (ppm)	Comment/Correct Commodity Definition

Tolerances listed under 40 CFR 180.418(a)(1):

Brassica, head and stem	2.0	2.0	[Brassica, head and stem, subgroup]

Brassica, leafy	14.0	14.0	[Brassica, leafy greens, subgroup]

Cattle, fat	0.05	1.0

	Cattle, meat	0.05	0.20	Harmonize with Codex MRL

Cattle, mbyp	0.05	0.05	[Cattle, meat byproducts]

Cottonseed	0.5	0.50	[Cotton, undelinted seed]

Goats, fat	0.05	1.0	[Goat, fat]

Goats, meat	0.05	0.20	[Goat, meat] Harmonize with Codex MRL

Goats, mbyp	0.05	0.05	[Goat, meat byproducts]

Hogs, fat	0.05	0.10	[Hog, fat]

Hogs, meat	0.05	0.05	[Hog, meat]

Hogs, mbyp	0.05	—	Residue data support removal of tolerance.

Horses, fat	0.05	1.0	[Horse, fat]

Horses, meat	0.05	0.20	[Horse, meat] Harmonize with Codex MRL

Horses, mbyp	0.05	0.05	[Horse, meat byproducts]

Lettuce, head	10.0	4.0	Residue data support reduction of tolerance.

Milk	0.05	2.5	[Milk, fat (reflecting 0.10 in whole milk)]

Onions, bulb	0.1	0.10	[Onion, bulb]

Onions, green	6.0	6.0	Residue data support a tolerance level of 3.0 ppm for zeta-cypermethrin / [Onion, green]

Pecans	0.05	0.05

	Sheep, fat	0.05	1.0

	Sheep, meat	0.05	0.20	Harmonizes with Codex MRL

Sheep, mbyp	0.05	0.05	[Sheep, meat byproducts]

Tolerances That Need To Be Proposed under 40 CFR 180.418(a)(1):

Cotton gin byproducts	--	11

	Egg	–	0.05

	Poultry, fat	–	0.05

	Poultry, meat	–	0.05	Harmonizes with Codex MRL

Tolerances That Need To Be Changed under 40 CFR 180.418(a)(2):

Hog, fat	1.0	0.10	Updated dietary burden supports lower tolerance level.

Hog, meat	0.2	0.05	Updated dietary burden supports lower tolerance level.

Hog, meat byproducts	0.05	None	Updated dietary burden eliminates need for tolerance.

Lettuce, head	10.00	None	Covered by Vegetable, leafy, except Brassica,  group 04.

Poultry, meat byproducts	0.05	None	Updated dietary burden eliminates need for tolerance.

E.	Regulatory Rationale

The Agency has determined that cypermethrin is eligible for reregistration provided that the risk mitigation measures and label amendments specified in this RED are implemented.  The following is a summary of the rationale for managing risks associated with the use of cypermethrin.

1.	Human Health Risk Mitigation

a.	Dietary, drinking water, residential, and aggregate risk mitigation

Cypermethrin dietary (food + drinking water), residential, and aggregate risks were below the Agency’s level of concern.  Moreover, the risk assessments are protective of the general U.S. population and all population subgroups, including infants and young children. Therefore, no mitigation is necessary for these scenarios.

Worker risk mitigation

i.	Handler risk mitigation

A number of application scenarios involving aerial, ground, or handheld equipment result in risks above EPA’s level of concern (MOE < 100 or ARI < 1). The following mitigation measures are necessary to address occupational risks that exceed the Agency’s level of concern:

Mixing, loading and applying liquid formulations

For motorized ground and aerial equipment, risks are below EPA’s level of concern at baseline and therefore, no mitigation is needed. For handheld application equipment, risks are below the level of concern with the addition of chemical resistant gloves.

For liquid formulations, chemical-resistant gloves are required for all hand-held application methods.

Mixing, loading and applying wettable powder formulations

For wettable powder formulations, all products must be repackaged in water soluble bags.

For wettable powder formulations, chemical-resistant gloves are required for all hand-held application methods.

One registrant with a wettable powder product for use in industrial, commercial, and residential settings has requested to reformulate their product into a dry flowable or prill formulation, rather than repackaging it into water soluble bags. Although risks can not be calculated due to lack of exposure data for dry flowables, EPA is confident that the risks to mixer, loader, and applicators of dry flowables products would be lower than those for liquid products, and thus below the Agency’s level of concern with the addition of chemical resistant gloves.

For dry-flowable or prill formulations, chemical-resistant gloves are required for all hand-held application methods.

Additional mitigation for aerial applications

Closed cockpits are required.

Human flagging is prohibited.

The human health assessment estimated risks to mixers, loaders and applicators making groundboom and aerial applications to sod farms at 0.74 lbs a.i./A. Application to sod farms is allowed through two Special Local Need registrations (FL SLN 890033, and CA SLN 840214). The Florida SLN allows application to Anheuser Busch sod farms using a soil injection rig only. The registrant (Syngenta) has been unable to verify whether or not this SLN is still in use and is not opposed to canceling it, since it is still tied to a former registrant’s product and has never been updated to reflect the change of product ownership. In any case, EPA does not anticipate risks of concern to human health (or aquatic organisms) from this soil injection use on sod farms.  The California SLN allows both groundboom and aerial application to sod farms. The registrant (FMC) has no record of this SLN and does not think it is currently active., since it is still tied to a former registrant'osed to cancelling on rig, only. The registrant has been unable to verify whether

Withdraw FL SLN 890033 and CA SLN 840214, for use on sod farms

Mixing, loading and applying granular formulations

  SEQ CHAPTER \h \r 1 In February 2006, a granular product was registered for use on lawns and outside of homes to kill fire ants (application to fire ant mounds).  Although no data were available to assess the risks of this use for cypermthrin, the Agency believes that the risks from this granular cypermethrin product will not exceed those for liquid products, which are below EPA’s level of concern for this scenario.  No mitigation is needed for this use.

Applying ready-to-use (RTU) formulations

No risks exceeded EPA’s level of concern, and no mitigation is needed.

ii.	Post-application risk mitigation

 Agricultural uses

EPA did not assess occupational postapplication risks to agricultural workers following treatments to agricultural crops, since no short- or intermediate-term dermal endpoints of concern were identified and long-term dermal exposures are not expected for tasks involving any of the registered crop use patterns.

As per the Worker Protection Standard, a restricted-entry interval of 12 hours is required for agricultural uses.

Non-agricultural (industrial, commercial, and residential) uses

EPA did not assess occupational post-application exposures and risks following applications to residential and commercial lawns, and in and around industrial, commercial, and residential premises, since no short- or intermediate-term dermal endpoints of concern were identified and long-term exposures are not expected for tasks involving any of the registered use patterns.

No new mitigation is required, but existing precautionary label statements and use directions intended to be protective of human health must be retained (see label table in Section V. for examples).

Additional recommendations based on incident reports

  SEQ CHAPTER \h \r 1 Based on documented incident reports involving cypermethrin, skin and eye protection is recommended for agricultural handlers making broadcast applications.  Bystanders should vacate indoor areas receiving treatment and the area should be appropriately ventilated afterwards before persons reenter the premises.  Further study is needed to determine whether labels should advise of potential allergy or asthma-like problems among sensitive individuals.

2.	Environmental Risk Mitigation

The Agency has conducted a screening-level ecological and environmental risk assessment for the registered agricultural uses of cypermethrin.  Based on the available data, the Agency has identified potential acute risks of concern to freshwater and estuarine/marine invertebrates and fish, benthic organisms, mammals, earthworms, and non-target insects, and potential chronic risks of concern to freshwater and estuarine/marine invertebrates, benthic organisms, and mammals.

Risk from non-agricultural uses of cypermethrin could not be quantitatively assessed at this time, but is expected based on the risks from agricultural uses, the high proportion of use of cypermethrin in outdoor non-agricultural areas (e.g. for nuisance pest control around structures and on lawns, and as a pre-construction termiticide), and the limited existing data showing the presence of cypermethrin in California urban creeks at concentrations toxic to benthic invertebrates. Mitigation to address the ecological risks from agricultural and non-agricultural cypermethrin applications is described below.

a.	Mitigation to Address Risks to Non-Target Organisms from Agricultural Uses

To address ecological risks from agricultural uses of cypermethrin, the following mitigation measures are required:

Decrease total yearly application rates, and increase re-treatment intervals

The maximum rate per application will be maintained at 0.1 lbs a.i./A for all crops. However, the following changes will be made to reduce the frequency of application and total pounds applied per year:

For cotton:

Limit the total amount of product applied to 0.4 lbs ai/A/year (reduced from 0.6 lbs ai/A/year).

Increase the minimum re-treatment interval to 5 days (increased from 3 days).

For pecans:

Limit the total amount of product applied to 0.5 lbs ai/A/year (reduced from 0.6 lbs ai/A/year).

Establish a minimum re-treatment interval of 7 days.

For head lettuce, head and stem brassicas (such as broccoli), leafy brassicas (such as canola), and bulb vegetables (such as onions):

Limit the total amount of product applied to 0.6 lbs ai/A/year.

Establish a minimum re-treatment interval of 7 days.

Prohibit high-rate, high-ecological-impact use sites

Remove the use sites:  agricultural uncultivated areas, fencerows, and hedgerows (application rate of 3.4 lbs ai/A) from product labels, and prohibit use on these sites

Prohibit use on rights-of-way

Prohibit use on sod farms

Require the following mitigation to reduce spray drift from agricultural applications

EPA understands the history of spray drift language development with the Pyrethroid Working Group (PWG), and the desire of registrants to maintain a level playing field among the pyrethroids with respect to spray drift restrictions. Since the current spray drift labeling for pyrethroids is over ten years old, EPA would like to update it as described below and in chapter 5 of this RED, and have all PWG pyrethroid products adopt these restrictions by early 2007.  EPA is willing to meet with the PWG to discuss any issues concerning these spray drift label statements, and welcomes comments from other stakeholders during the 60-day post-RED comment period.

For groundboom and aerial applications, use medium or coarser spray nozzles

For motorized ground or aerial applications, apply only when the wind velocity is 3 to 10 mph for all crops other than cotton; for cotton, apply only when the wind velocity is 3 to 15 mph

Do not make ground or aerial applications during temperature inversions

For airblast applications to tree crops, direct spray into the canopy, and turn off outward pointing nozzles at row ends and when spraying outer two rows

For groundboom, chemigation, or airblast applications, do not apply within 25 feet of water bodies or aquatic habitat

For aerial applications, do not apply within 150 feet of water bodies or aquatic habitat; increase this no spray buffer zone to 450 feet when making an ultra low volume (ULV) application

For aerial applications, do not release spray at a height greater than 10 feet above the ground or crop canopy, when spraying within 1000 feet of water bodies or aquatic habitat

See Section V and the label table for required spray drift label statements.

Require the following mitigation to reduce run-off from agricultural fields

Construct and maintain a 10-foot-wide vegetative filter strip of grass or other permanent vegetation between the field edge and any water body or aquatic habitat (USDA, NRCS. 2000. Conservation Buffers to Reduce Pesticide Losses.  Natural Resources Conservation Service. Fort Worth, Texas.)

Mitigation to Address Risks to Non-Target Organisms from Non-Agricultural Uses

Estimating risk from non-agricultural uses of pyrethroids

The Office of Pesticide Programs (OPP) strives to estimate pesticide exposure through all significant routes of exposure from both agricultural and non-crop uses. However, the ecological risk assessments for pyrethroid insecticides focus predominantly on the agricultural uses for these insecticides, because pesticide transport models are available to estimate potential aquatic exposure.  Based on laboratory toxicity tests with terrestrial and aquatic animals, aquatic exposure would be more likely to cause adverse effects in the environment.

However, sales data indicate that non-crop uses of the pyrethroids comprise a much larger fraction of total use than agricultural uses.  The use of pyrethroids in urban and suburban settings has increased since the phase-out of these uses of the organophosphate insecticides diazinon and chlorpyrifos.  Sales data indicate that the majority of urban use of cypermethrin is for structural pest control, such as for control of termites or ants.  Other outdoor non-crop uses include landscape maintenance, and homeowner lawn and garden use.  Indoor uses include nuisance insect control, and termite applications.

For pyrethroids with relevant indoor uses (not including cypermethrin), the Agency uses a “down-the-drain” model to perform a screening-level aquatic risk assessment.  In these simulations, waste water containing pesticide residue flows into a building drain and passes through a sanitary sewer and publicly owned treatment works (POTW) before being discharged to surface water. However, no analogous exposure model has been developed to allow a similar screening-level assessment for pesticides applied in an outdoor urban setting, like cypermethrin. As a result, the Agency has had to take a qualitative approach to characterize the potential aquatic risk from urban and suburban use of pyrethroids.