UN I TE D STATES ENV IR ON M ENTAL PROTE C T I ON AGENCY WAS HI NGTON , D

. C. 20460



### JAN 23 2013 O F FI C E O F CHE\ 11 CAI.. SA FEn '**A~ D**  POI.. L l TION PRE\ 'E YJ' I O N

.O Ec;:ISION MEMORANDUM

SU BJECT:

: F ROM:

TO Reg i strat i o n ofNew Active Ingred i e n t Alpha- Cy permethrin
Lois Ross i , Directo r

## ~-0**\(~** Regis t ration DivisiQl/ \ 

## \W>\ \3

Steven Bradbury , Ph

. D. , Director Office of Pesticide Programs

Th i s mem orandu m recommends that you concur on the registration a n d th e establ i s hment of w l e · ances for t he new active ingredient alp h a-cypermethrin for u ses on alfa l fa , bras s i ca vegetables, citrus r ru il5, corn (fie ld , pop , see d , and sw eet) , cotto n , cucurbits, fruiting vegetab l e s, leafy vegetables , legume**egc~tables ,**  ric e, ro o t and tuber vegetables, soybeans , sugar beets , tre e nuts , and wheat. A summary of the h u rr
. a n h ea l th and ecological risks is included in the attached Regist r ation Decisi o n D ocu me n t. The Science Div

. sio n s ha ve rev i ewed a ll available data and the R eg i stratio n D i vi s i on ha s concluded that the criteria for
u n cc mditional r eg i stration under FIFRA Section 3(c) (5) have been met.
;t u:c; : OMMENDAT I ONS
I rec o m mend that you conc u r with t h e establishment of tolerance s and the uncond i tio n al**egi tration**  ofthe new active ingredie nt a lph a
- cypermethr i n u nder FIFRA Sectio n 3(c) (5).

Concur:

__ __**~~~===E~ ~~~~~** **---- ~**  S even Braabury, Ph

. D. , Director Office of Pesticide Programs

Nonconc ur:
------------ -------- ---------- -- Steven B r adbury, Ph.D. , Director

Attcchments:, Regis)Tation Decision Document Pesticide Tolerances , Fina l Rule Summary Documen t Office o f Pesticide P r ograms2 I. REGULATORY DECISION The United States Environmental Protection Agency (EPA or the Agency) is granting the unconditional registration of the new pesticide active ingredient (a.i.) alpha

- cypermethrin for use on a variety of crops. The registration includes uses on alfalfa, b r assica vegetables, citrus fruits, corn (field, pop, seed, and sweet), cotton, cucurbits, fruiting vegetables, leafy vegetables, legume vegetables, rice, root and tuber vegetables, soybeans, sugar beets, tree nuts, and wheat. The registration of alpha

- cypermethrin relies on alpha

- cypermethrin data, as well as previously submitted data for the related registered insecticides, cypermethrin and zeta

- cypermethrin. This is the first registration for alpha

- cy permethrin in the United States.
II. INTRODUCTION/BACKGROUND Alpha

- cypermethrin was developed by BASF Corporation for use on a variety of crops. Additionally, BASF has petitioned for the establishment of tolerances for residues of alpha

cypermethrin in or on various commodities , at the same levels as tolerances established for zeta

- cypermethrin in those commodities. Alpha

- cypermethrin is a broad spectrum insecticide, effective agains t target pests through contact and ingestion. Alpha

- cypermethrin is a type II synthetic pyrethroid. Pyrethroids disrupt the voltage

- gated sodium channels in the nervous system, resulting in neurotoxicity . Alpha

- cypermethrin, like other cypermethrin s , is active against a wide range of insect pests important in agricultural production.
A lpha

- cypermethrin end

- use product (BAS 310 40 I) contains 0.83 lb ai/gal (10.9%) ai , and is to be applied for preventative and curative control of a number of significant insect pests on a variety of different crops. For most crops, the seasonal maximum application rate per year is 0.075 lb ai/acre. While most applications are post

- emergence foliar sprays using ground or aerial equipment, there are also uses for pre

- plant or soil

- incorporated applications and/or chemigation. BAS 310 40 I (Fastac EC Insecticide) is labeled as a Restricted Use Pesticide (RUP) , for agricultural uses only. Similar active ingredients, c ypermethrin and zeta

- cypermethrin are registered in many countries world

- wide for numerous agricultural, residential and public health uses , and both contain in part the same isomeric components that make up alpha

- cypermethrin

. R egistration of alpha

- cypermethrin relies on alpha

- cypermethrin data , as well as p reviously submitted data for the related registered insecticides, cypermethrin and zeta

cypermethrin. Cypermethrin, zeta

- cypermethrin and alpha

- cypermethrin are isomer mixtures of the same chemical. Cypermethrin consists of a mixture of eight isomers (fo ur diastereoisomeric pairs). Zeta

- cypermethrin is composed of four of the eight isomers of cypermethrin, and also contains one of the isomers in alpha

- cypermethrin. Alpha

cypermethrin consists of two of the four cis

- isomers of cypermethrin. S tudies cond ucted to support the registrations of cypermethrin and zeta

- cypermethrin are applicable to the registration of alpha

- cypermethrin. Therefore , the following discussions r egarding “cypermethrin ” include cypermethrin, alpha

- cypermethrin and zeta cypermethrin as a group of similar ly related active insecticide ingredients.3 III. HUMAN HEALTH RISK
Introduction: The cypermethrins have been evaluated for a variety of toxic effects in experimental toxicity studies. In developing a human health risk assessment, EPA has examined the available hazard and exposure information regarding alpha

- cypermethrin, as well as information for cypermethrin, zeta

- cypermethrin, and pyrethroid chemicals as a class. Although cypermethrin, alpha

- and zeta

- cypermethrin are separate active ingredients with different end

- use products, they were included together in the hazard evaluation due to structural and toxicological similarities and comparable toxicity profiles. For risk assessment purposes, the active ingredients are considered equally toxic and the most protective endpoints and points of departure (PODs) for each study type have been selected for risk assessment. In addition, the overall risk assessment consider ed not only the exposure associated with the proposed food uses fo r alpha

- cypermethrin, but also the potential dietary and drinking water contribution and residential exposure from existing registered uses of cypermethrin and zeta

- cypermethrin.
A. Toxicological Effects and End Points Behavioral changes commonly seen with type II pyrethroids were consistently noted in the toxicological database. These included tremors, gait abnormalities, limb conditions, ataxia, and hypersensitivity. Additional toxic effects observed with the cyperme thrins were changes in body weight, mortality in a few studies with rats and dogs, and an increased incidence of lung tumors in female mice after chronic exposure. The select ed toxicity endpoints and points of departure for risk assessment we re b ased on the proposed use patterns for the cypermethrins, and the expected exposure profile for dietary, dermal, inhalation , and incidental oral exposures.
T he toxicity endpoints for cypermethrin, zeta

- cypermethrin, and alpha

- cypermethrin (as a group) are based o n clinical signs of neurotoxicity consistent with type II pyrethroids. The available studies include multiple species, study designs, and durations. Moreover, the acute exposure or bolus dosing studies generally result in lower , no observable adverse eff ect level s ( NOAEL ) compared to longer term dietary administration studies, consistent with other pyrethroids in this class. Because uncertainty associated with the POD is propagated throughout the risk assessment, one of the key factors in POD selection i s the robustness of the dose

- response data. The guideline experimental toxicology studies available for the cypermethrins are generally high quality and were consider ed in the POD selection process and in the weight of the evidence evaluation. Observatio ns of tremors, gait abnormalities, limb conditions, and hypersensitivity were prominent findings in the guideline experimental toxicology studies and were considered in the point of departure (POD) determination. However, guideline studies typically have only three treatment groups and often do not evaluate clinical signs at the time of peak effect. Moreover, scoring metrics for behavioral parameters vary widely among guideline studies. Given the multiple strengths associated with the design of the Wolan sky et. al. ( 2006 ) study and the resulting4 well

- defined dose

- response curve, it was determined that the study provided the most robust data set for extrapolating risk from the cypermethrin s
. The Wolansky study was determined using a benchmark dose (BMD) analysis conducted in accordance with standard Agency assumptions with respect to the benchmark response (BMR). Wolansky et al. ( 2006 ) measured motor activity at the time of pea k effect after exposure to 11 pyrethroids, including cypermethrin. Dose

- response relationships were determined using 6

- 11 doses per pyrethroid (6 doses used for cypermethrin) and 3

- 18 rats per dose group ( 8 animals/group used for cypermethrin) , minimizing variability and increasing the confidence in the body mass dose ( BMD ) estimates determined from this study. Moreover, each pyrethroid was evaluated by the same scientist , thus decreasing some of the variability associated with neurobehavioral measures. Acute Dietary (all populations)
EPA selected the POD and endpoint from the acute oral Wolansky study in rats for acute dietary exposure. Acute dietary risk assessment was performed using the BMDL 1SD value of 7.16 mg/kg , based on decreased locomotor activity at the BMD 1SD value of 11.20 mg/kg. There is no increase in hazard from repeated exposures to the cypermethrins; therefore, the acute dietary exposure assessment is protective of chronic dietary exposures since acute exposure levels are higher than chronic exposure levels. Accordingly, a dietary exposure assessment for the purpose of assessing chronic dietary risk was not conducted. Incidental Oral (Short
- term) For the purpose of assessing potential risk associa ted with incidental oral exposure to children re

- entering treated areas, EPA selected the dose (POD) and endpoint from the acute oral Wolansky study in rats. Incidental oral risk assessment was performed using the BMDL 1SD value of 7.16 mg/kg, based on dec reased locomotor activity and the BMD 1SD of 11.20 mg/kg. The decreases in motor and locomotor activity are considered potential single

- dose effects because they were observed within the first hours following dosing. The Wolansky study is a very robust st udy with 6 doses, uses a sensitive vehicle and volume to determine a BMDL and therefore provides a more accurate point of departure than other studies considered for incidental oral endpoint and dose selection. Dermal (Short
- and intermediate
- term) A dermal assessment was not conducted for children or adults. No systemic effects were observed in the 21

- day rat study with zeta

- cypermethrin up to the limit dose. No systemic effects were observed with cypermethrin in animals with non

- abraded skin up t o the highest dose tested (1000 mg/kg/day in the rat and 200 mg/kg/day in the rabbit). Additionally, there are no developmental concerns. Based on the exposure profile, EPA does not anticipate long

- term dermal exposure for adults or children. A dermal absorption study for alpha

- cypermethrin in the rat is available for consideration. Typically pyrethroids have a low absorption value of ≤ 5%. Combined with the high rate of metabolism, the amount of parent available to interact with sodium chann el5 is minimal and therefore neurotoxic effects are not routinely observed in dermal studies. The absorption rate in the alpha

- cypermethrin study is slightly higher at 13%. However, systemic effects were not observed in the rat at 1000 mg/kg/day. Since r at skin is typically more porous to xenobiotics compared to human skin, it’s highly unlikely sufficient cypermethrin will penetrate human skin in sufficient quantities to cause neurotoxicity. Furthermore, pyrethroids are lipophilic and therefore much of t he measured radioactivity measured in the skin was captured in the upper dermal layers and not available for absorption. Based on these factors just discussed, EPA does not anticipate systemic toxicity via the dermal route of exposure. Inhalation (Short
- and intermediate
- term)
A route

- specific 21

- day rat inhalation study with cypermethrin was used to assess short

and intermediate

- term inhalation exposure. The NOAEL of 0.01 mg/L and the lowest observable adverse effects level ( LOAEL ) of 0.05 mg/L were based on increased salivation. This dose and endpoint are appropriate since the effects were seen following exposure via the route (inhalation) and duration (short

- and intermediate

- term) of concern. Additionally, the effects seen in t he inhalation study are consistent with the pyrethroid profile and are protective of neurotoxicity. For cypermethrin, human equivalent concentration s ( HEC ) s for the inhalation NOAEL were calculated for use in margin of exposure ( MOE ) calculations, based on the methods and dosimetry equations described in EPA’s reference concentration (RfC) guidance (1994). The regional deposited

- dose ratio (RDDR), which accounts for the particulate diameter (mass median aerodynamic diameter [MMAD] and geometric standard deviation [ g ] of aerosols), can be used to estimate the different dose fractions deposited along the respiratory tract. The RDDR is also based on interspecies differences in ventilation and respiratory

tract surface areas. Thus, the RDDR can be used to adjust an observed inhalation particulate exposure of an animal to the predicted inhalation exposure for a human. For the 21

- day inhalation study, a RDDR was estimated at 3.1 based on the reported MMAD of 2.63 μm and geometric standard deviation ( g ) of 1.8 7 and the respiratory

- tract surface area of the rat relative to the human. Since the rat inhalation study was carried out for 6 hr/day for 5 days/week, the only exposure adjustment made was in the assumption of 8 hrs/day for human occupational exposures. The resulting HEC is 0.023 mg/L. For human residential exposure, 24 hrs/day was assumed and the HEC is 0.008 mg/L . For the current risk assessment, the use of 24 hours of exposure to calculate an HEC is considered protective and very conservative since h andler exposure via the inhalation route is expected to be less than 24 hours. Human equivalent doses of 1.10 mg/kg/day for occupational and 1.15 mg/kg/day for residential were also calculated and used for risk assessment. Based on the exposure profile, EPA does not anticipate long

- term inhalation exposure for adults or children. Prenatal and postnatal sensitivity. There was no evidence of increased qualitative or quantitative susceptibility in developmental toxicity studies in the rat and rabbit and a rat two

- generation reproductive toxicity study. A developmental neurotoxicity (DNT) study with zeta

- cypermethrin did6 indicate some potential increased sensitivity in the offspring based on body weight changes in pups in the absence of treatment

- related effects in maternal animals. T he decrease in body weight of the young is comparable to adults; however, it was considered adverse in the young but not in the adults. This disparity in interpretation leads to an apparent increase in sensitivity in the young ; however, concern is reduced since the magnitude of body weight decrements was similar in adult and young animals. The results from the DNT study are very similar to results observed in the reproduction studies where body weight changes (decreased BW gai n) were seen in maternal and offspring animals at doses similar to those in the DNT study, with no indication of increased susceptibility. Therefore, there is no residual concern for effects observed in the study. The FQPA factor of 3X which is being ret ained by the Agency for all pyrethroids is considered adequately protective of potential effects of body weight for children <6 years of age exposed to the cypermethrins, including zeta

- and alpha

- cypermethrin.

. Ca ncer Classification and Risk Assessme nt Recommendation for the Cypermethrins

Cypermethrin is classified as a Group C “Possible human carcinogen”, based on an increased incidence of lung adenomas and adenomas plus carcinomas combined in females in a mouse carcinogenicity study. The presence of common benign tumors (lung adenomas), in one species (mice) and one sex (female), with no increase in the proportion of malignant tumors or decrease in the time

- to

- tumor occurrence, together with the lack of mutagenic activity, was not considered strong enough to warrant a quantitative estimat ion of human risk. Taking into account all of this information, the Agency has determined that quantification of risk using a non

- linear approach (i.e., aPAD or aRfD) will adequately account for all chronic toxicity, including carcinogenicity that could r esult from exposure to the cypermethrins. While the Agency would typically use a cPAD to protect for cancer concerns, use of the aPAD is protective because increasing toxicity with increasing duration of exposure is not demonstrated for the cypermethrins. The NOAEL observed in the mouse cancer study in which tumors were observed is 14 mg/kg/day, 2

- fold higher than the POD used for acute risk assessment. The LOAEL in the mouse cancer study is 57 mg/kg/day based on liver effects, not tumor formation. The t umors were seen at 229 mg/kg/day. The acute point of departure (POD) of 7.16 mg/kg/day selected for risk assessment is 32 fold lower than the dose that induced lung tumors in mice. Only the mouse study with cypermethrin resulted in tumor formation , no evi dence of carcinogenicity was observed in cancer studies in rats with cypermethrin or mice with alpha

- cypermethrin.
B. Food Quality Protection Act (FQPA) Safety Factor (SF) Cypermethrin, alpha

- and zeta

- cypermethrin exposure to children <6 years old is expected , and must be considered in the context of the pyrethroids as a class. For infants and children less than six years of age, EPA is reducing the FQPA safety factor to 3X based on the increased quantitative susceptibility seen in the scientific lite rature related to pyrethroid pharmacokinetics, as summarized in the Agency’s recently completed pyrethroid cumulative assessment, and section 4.4 of the alpha

- cypermethrin human health risk7 assessment. The FQPA safety factor was reduced to 1X for women of child bearing age (as well as for all adult populations and children ≥ 6 years).
C. EPA’s Levels of Concern (LOC) for Margin of Exposure (MOE)
EPA ’s level of concern for occupational and residential risks is based on the various uncertainty and safet y factors retained or applied for specific routes of exposure. The LOCs relevant for risk assessment for the cypermethrins are described in the table below. For inhalation risk assessments, the 10X interspecies factor was reduced to 3X to account for int erspecies differences, in accordance with the RfC guidance. The only exposure pathway for adults and children greater than 6 years old is via inhalation, for which a 30X uncertainty factor has been retained. The intra

- species variability factor of 10X is combined with an interspecies extrapolation factor of 3X, based on the use of a human equivalent dose for inhalation risk assessment. For children under 6 years old, exposed via the inhalation route, the LOC is 100, based on a 10X factor for intraspecies variability, 3X for interspecies extrapolation, and 3X for juvenile sensitivity. For children exposed via the oral route, the LOC is 300, based on the traditional 10X factors for intra

- species variability and interspecies extrapolation, and the additiona l 3X FQPA factor.
Route LOC Occupational Dermal Exposure NA Occupational Inhalation Exposure 30X Residential Incidental Oral Exposure < 6 years old: 300X Residential Dermal Exposure (Adults/Children) NA Residential Inhalation Exposure ≥ 6 years old: 30X < 6 years old: 100X

D. Residential Risk There are no currently proposed or registered residential uses associated with alpha

cypermethrin; however, there are registered residential uses for racemic cypermethrin and zeta

- cypermethrin that have been re

- assessed to reflect updates to the Agency’s 2012 residential SOP’s along with policy changes for body weight assumptions and inhalation rates

. 1. Registered Cypermethrin Residential Handler Exposure/Risk Estimates : The Agency has determined that s hort

- term exposures are likely to occur in a residential setting; however, the cypermethrins do not increase in potency with repeated dosing. Therefore, only single

- day residential exposures were assessed. Racemic cypermethrin and zeta

- cypermethrin are r egistered for use on a variety of indoor and outdoor residential environments, including: lawns, gardens, pets, and indoor surfaces and spaces, in a number of formulations. The Agency identified the residential scenarios with the highest exposure estimat es and used these to8 quantitatively evaluate residential exposure and risk. Risk estimates associated with the identified worst

- case scenarios are protective for all other residential handler scenarios. These include: mixer/loader/applicator scenarios us ing hose end sprayers on turf, using backpack sprayers on turf and gardens, using manually pressurized hand wands for indoor surfaces, and applications via aerosol cans for indoor surfaces and space. MOE’s for all scenarios were >6,100 and therefore, thes e exposure do not exceed the a gency’s level of concern.
2. Registered Cypermethrin Residential Post

- Application Exposure/Risk Estimates : There is potential for post

- application exposure for individuals as a result of being in an environment that has been previously treated with cypermethrin. The Agency determined that the only potential post

- application exposure pathways of concern are incidental oral for children and post

- application inhalation exposure for adults and children resulting from indoor crack and crevice applications made with a manually pressurized handwand. MOE’s for all scenarios were >1,000 and therefore, these exposure s do not exceed the Agency’s level of concern.
E. Water Residue Profile and Drinking Water Risk
I n general , cypermethrin is applied at a maximum seasonal use rate (0.6 lb ai/A for most uses) 4X that of zeta

- cypermethrin (0.15 lb ai/A for most uses), which is 2X the maximum proposed seasonal rate for alpha

- cypermethrin (0.075 lb ai/A). As a class of chemicals, the pyrethroids have low solubility in water and a high affinity to bind to soils. Given these physical/chemical properties, it is unlikely that oral exposure from drinking water will be a major pathway of exposure. The water solubility of alpha

- cyperm ethrin (technical active ingredient, 98.0%), at 20°C in 0.01M buffers (at pH values of approximately 4 to 9), ranges from 4.59 to 7.87 μg/L. In distilled water alone , the solubility is slightly less (2.06 μg/L). The solubility is not strongly dependent o n pH values within the range of 4 to 9. It is likely that differing ionic strengths account for the differences between the solubility of alpha

- cypermethrin in pure water, and the solubility in the buffer solutions.
The assessment provided estimated r esidues of alpha

- cypermethrin in drinking water from the use of cypermethrin s on cotton. The cotton use results in the highest estimated drinking water concentrations (EDWCs) for all assessed use scenarios, including those associated with the petitions cu rrently under review. No monitoring data are currently available to further characterize potential drinking water exposure. In the dietary risk assessment conducted to support the proposed uses and label changes, EPA incorporated the surface water EDWCs directly into the dietary model, since surface water estimates were higher than those provided for ground water. In the acute assessment, an EDWC of 3.77 ppb was used. For the purpose of assessing short

- term aggregate risk (i.e., food, drinking water, an d residential exposures) the chronic water concentration of value 0.066 ppb was used to assess the contribution to drinking water. The use of the surface water values in the dietary assessment is therefore protective of potential exposure through ground w ater sources of drinking water.9 F. Dietary Residue Data Used and Risk Assessment Partially refined (probabilistic) dietary exposure assessments were performed in order to determine the exposure and risk estimates which result from the use of cypermethrin , alpha

cypermethrin, and zeta

- cypermethrin on the crops listed under 40 CFR 180.418 and the proposed new uses. Anticipated residues from USDA Pesticide Data Program (PDP) monitoring data, field trial data, empirical processing factors, and percent

- crop t reated estimates were used where appropriate. For the acute assessment, residue distributions were generally used when PDP and field trial data were included. In order to assess short

- term aggregate risk to the cypermethrins, average dietary exposure est imates (i.e., food and drinking water) were calculated. Because the endpoint from the acute study is protective of endpoints from repeat dosing studies, including cancer risks, a chronic dietary risk assessment was not conducted.
Th e current assessment updates prior assessment s by 1) taking into account revised toxicological endpoints, requiring a refined acute dietary exposure assessment 2) adding the new proposed uses of alpha

- cypermethrin and zeta

- cypermethrin , and 3) incorporation of updat ed anticipated residue levels and percent crop treated estimates where appropriate. N o new residue data were needed to support alpha

- cypermethrin, since the proposed tolerances are being bridged from existing uses. EPA considers the dietary assessments to be partially refined, but at the same time, very health

- protective. Refinements were made to most of the risk drivers in the assessment; however, in many cases, including the proposed new uses of alpha

- cypermethrin, the analysis generally relied upon f ield trial data , with some refinement that included PDP residues data and estimates of the percent crop treated (PCT) for only some commodities

. EPA has learned from past experience that monitoring data are often significantly lower than field trial data. Monitoring data more accurately represent the residue levels to which people will actually be exposed to pesticide residues in their diets. Field trial data represent conservative estimates of exposure. The assessment is also conservative in that toler ance
- level residues were used for many commodities in the acute assessment. Percent crop

- treated estimates and monitoring data were not available for two of the risk drivers for children less than 6 years of age, oats and milk. As a result, 100% crop tre ated ( CT ) was used for these commodities. If usage estimates were available and had been used, the risk estimates for these population subgroups would have been lower. Due to the many conservative assumptions made in this assessment, in particular, the use of field trial data (as opposed to monitoring data) for many commodities, EPA is confident that the acute and average dietary assessments overestimate exposures to the general U.S. population and all population subgroups. Acute dietary risk estimates are below the Agency’s level of concern for all population subgroups. Acute risks for all infants and children 1

- 2 years old , the highest

- exposed population subgroups are estimated to be 87% of the aPAD. Chronic and cancer dietary risk assessments were not conducted for cypermethrins. Because of the rapid reversibility of the most sensitive neurotoxicity endpoint used for quantifying risks, there is no increase in hazard with increasing dosing10 duration, and therefore, the acute dietary endpoint is prote ctive for chronic and cancer dietary exposures.
G. Aggregate (Food + Drinking Water + Residential ) Risk In accordance with FQPA, the Agency must consider and aggregate cypermethrin pesticide exposures and risks from three major sources: food, drinking water, and residential exposures. In an aggregate assessment, exposures from relevant sources are added together and compared to quantitative estimates of hazard. For acute aggregate risk, the Agency determined that only food and water acute risks should be aggregated, as one

- day residential exposures are not routinely assessed. Acute dietary risks have already been discussed. For assessing short

- term aggregate risk, the average dietary exposure estimate was used since it represents a background exposur e level from food and drinking water that may co

- occur with residential exposures. Dietary and oral (hand to mouth) risks for children and dietary and inhalation risks for adults were combined in this assessment, since the toxicological endpoints were the same. However, the LOC values for children younger than 6 years old were different for oral and inhalation exposure, with an incidental oral LOC of 300, and an inhalation LOC of 100. Likewise, the inhalation and dietary LOCs for adults were different, w ith an inhalation LOC of 30 and a dietary LOC of 100

. T herefore, the respective risk estimates are combined using the aggregate risk index (ARI) approach. When this approach is used, the risks are not of concern provided the calculated ARI is greater tha n 1. The aggregate ARI for exposure of children was 2.3 (lowest individual ARI of 3.3 for hand

- to

- mouth residential exposure) and the aggregate ARI for adults was 56 (lowest individual ARI of 78 for dietary exposure). T herefore aggregate risks are not of concern. An intermediate/chronic aggregate risk assessment was not conducted, because the cypermethrins are acutely toxic and do not increase in potency with repeated dosing (discussed previously). Because acute toxicity studies can assess the risk for longer term studies, it is assumed that the acute and short

- term intermediate aggregate assessments are protective for intermediate

- term and chronic aggregate risks anticipated from cypermethrin exposure.
H. Cumulative Effects The Agency is required to c onsider the cumulative risks of chemicals sharing a common mechanism of toxicity. The Agency has determined that the pyrethroids and pyrethrins share a common mechanism group. The members of this group share the ability to interact with voltage

- gated sod ium channels ultimately leading to neurotoxicity. No cumulative risks of concern were identified allowing the Agency to consider new uses for pyrethroid actives. The cypermethrins are included in the common assessment group of the pyrethroid/ pyrethrin c umulative risk assessment. However, t he new uses of alpha

- cypermethrin will not impact the cumulative assessment because: 1) the alpha

- cypermethrin application rates are lower than the zeta

- cypermethrin rates and are expected to result in lower residue le vels;11 and 2) zeta

- cypermethrin has already been registered for use on the crops proposed for alpha

- cypermethrin and those uses were incorporated into the cumulative assessment. Additionally, no new residential uses are proposed, so the residential cumulat ive assessment will not be impacted. This is not the first pyrethroid registered under the Agency’s finalized cumulative risk assessment for pyrethroids and pyrethrins (dated October 4, 2011, Docket EPA

- HQ

- OPP

2011

- 0746) . Another new chemical, flumethrin, was registered earlier in 2012 for non

- food uses as a pet collar. The published risk assessment for flumethrin (dated March 6, 2012, Docket, EPA

- HQ

- OPP

- 2011

- 0013) also has a more detailed discussion of how the cumulative risks were assessed for pyrethroids and how it has affected and will affect subsequent assessment of new pyrethroid chemicals and new uses.

I. Occupational Risk Based on the anticipated use patterns and current labeling, types of equipment and t echniques that can potentially be used, short

- and intermediate

- term occupational handler exposure is expected from the proposed uses; however, alpha

- cypermethrin does not increase in potency with repeated doses. Therefore, only single

- day exposures are a ssessed. The quantitative exposure/risk assessment developed for occupational handlers is based on the following scenarios:

• Mixing/Loading Liquids for Groundboom Application,

• Mixing/Loading Liquids for Aerial Application,

• Mixing/Loading Liquids for Chemigation,

• Mixing/Loading Liquids for Airblast Application,

• Applying Sprays with Groundboom Equipment,

• Applying Sprays with Aerial Equipment,

• Applying Sprays with Airblast Equipment, and

• Flagging for Aerial Applications. No handler exposures ar e expected from applying sprays via chemigation systems.
The calculated handler MOEs are all higher than EPA ’s level of concern of an MOE of 30, with the lowest MOE of 14,000 identified for a mixer/loader preparing sprays for aerial application to high acre age. Occupational Post

- application Inhalation Exposure/Risk Estimates : Based on the Agency's current practices, a quantitative post

- application inhalation exposure assessment was not performed for alpha

- cypermethrin at this time primarily because of the low acute inhalation toxicity (Toxicity Category III), low vapor pressure (2.55 x 10 - 9 mm Hg at 25*C), and the low proposed use rate (0.025 lb ai/A). However, there are multiple potential sources of post

- application inhalation exposure to individuals performing post

application activities in previously treated fields. Although a quantitative occupational post

- application inhalation exposure assessment was not performed, an inhalation12 exposure assessment was performed for occupational/commercial handl ers. Handler exposure resulting from application of pesticides outdoors is likely to result in higher exposure than post

- application exposure. As discussed previously, all MOE’s were above the Agency’s level of concern Occupational Post

- application Derm al Exposure/Risk Estimates : Based on the use pattern and directions, short

- and intermediate

- term dermal exposures are expected for workers conducting post

- application activities on agricultural crops. Although short

and intermediate

- term dermal post

- a pplication exposures are expected for workers re
entering treated fields, there is no toxicity associated with dermal exposure to the cypermethrins, and therefore a quantitative dermal post

- application exposure assessment was not performed. EPA does not anticipate post

- application dermal risks after exposure to alpha

- cypermethrin. Th e REI specified on the registered label is based on the acute toxicity of alpha

- cypermethrin technical material which is classified as Category III for acute dermal and eye i rritation, and Category IV for skin irritation. Based on the acute toxicity profile of alpha

- cypermethrin, the 12

- hour REI appearing on the proposed label is appropriate to protect agricultural workers from post

- application exposures to alpha

cypermethrin

.

I I I. ECOLOGICAL AND ENVIRONMENTAL RISKS

A. Environmental Fate
Persistence : Laboratory studies have indicated that alpha

- cypermethrin degrades through a combination of biotic and abiotic reactions and is slightly to moderately persistent in the environment, with half

- lives ranging from 2 to 67 days. Alpha

cypermethrin is considered immobile in soils based on the FAO soil mobility classification (K oc as high as 144,662 L/Kg) and its potential to leach into groundwater is low ( U SEPA, 2006 a ). If released to water, alpha

- cypermethrin will rapidly partition to the sediment compartment which acts as an environmental sink for this compound. Alpha

- cypermethrin may bioconcentrate moderately in fish (BCF = 448X in whole fish), with mod erate depuration. In terrestrial field dissipation studies alpha

- cypermethrin was not very persistent in soils and did not leach (half

- lives 1

- 2 weeks). In supplemental aquatic field dissipation studies (zeta

- cypermethrin), the chemical appears to persis t in the sediment, with reported half

- lives of 126 and 181 days in LA and CA, respectively. Transport : Alpha

- cypermethrin is considered immobile in soil. Soil organic carbon adsorption coefficients (K oc ) for cypermethrin s ranged from approximately 21,00 0 to 328,500 L/Kg in four soils (sand, sandy loam, silty loam and clay). If released into water, cypermethrin s rapidly partitions to the sediment column. The tendency to adsorb to soil and sediment along with the relatively low vapor pressure (2.5x10 - 9 mm Hg) and Henry’s law constant (3.4x10 - 7 atm

- m 3 /mol), indicates that volatilization from water and soil will not be an important transport process.13 B ioconcentration : The reported value of log octanol/ water partition coefficient of 6.4 suggests that alpha

- cypermethrin has the potential to bioaccumulate in aquatic organisms assuming that chemical metabolism is negligible. Maximum BCFs for the alpha

- cypermethrin are 161x for edible tissue, 883x for viscera, and 448x for whole fish (MRID 42868203, study conducted with racemic cypermethrin) . Depuration appeared to be moderately slow, with ~10

- 15% of the initial residues remaining after 21 days. Thus, it appears that there is potential for bioaccumulation/ bioconcentration in aquatic organisms. However, a lpha

- cypermethrin is being metabolized extensively in the fish, which suggests a reduced potential for alpha

- cypermethrin to biomagnify in terrestrial organisms.
D egr a dation : The major degradation products of the base catalyzed hydrolysis of cypermethri n were cis

- and trans

- DCVA (maximum 79% at 120 hours or study duration) and 3

- phenoxybenzaldehyde (maximum 65% at 120 hours). Photolysis of cypermethrin in distilled water occurs slowly, but the rate of degradation appears to be enhanced in natural water s, which contain humic and fulvic acids. A photolysis half

- life of 5 days was observed for alpha

- cypermethrin in pH 7 aqueous buffered solution exposed to sunlight in California from March to April. Shorter half

- lives on the order of less than 1 to 4 day s were observed for cypermethrin dissolved in river water, seawater and distilled water with 1% humic acid exposed to sunlight (Takahashi et al. 1985). The half

- life for thin films of cypermethrin in a sandy loam soil matrix was approximately 55 days; how ever, degradation was also observed in control samples and the dark control corrected half

- life is over 100 days. The only transformation product observed was cyperamide, at 13.3% at the end of the study (35 days). Cypermethrin degraded with a half

- life of approximately 60 days in a fine sandy loam soil maintained at 25 o C and held under aerobic conditions (28 days for alpha

- cypermethrin). Carbon dioxide and a mixture of cis

- and trans

- DCVA (maximum 24% at 62 days in a 150 day study) were the major degr adation products. Aquatic exposure : Based upon the environmental fate properties of alpha

cypermethrin and the proposed application methods, alpha

- cypermethrin use may lead to surface and ground water contamination. It is possible for alpha

- cypermethrin to reach surface water through spray drift. Furthermore , alpha

- cypermethrin may penetrate the foliar canopy during application and/or wash off plant surfaces following application to the soil surface and adsorb to soil particulates. These particles can move off

- site by soil erosion to adjacent water bodies. Terrestrial exposure : It is possible for alpha

- cypermethrin to reach a wide variety of terrestrial environments through direct spray, spray drift, and soil erosion.

B. Ecological risk. Ecological risk characterization integrates the results of the ex posure and ecotoxicity data to evaluate the likelihood of adverse ecological effects. The means of integrating the14 results of exposure and ecotoxicity data is called the quotient method. For this method, risk quotients (RQs) are calculated by dividing ex posure estimates by ecotoxicity values, both acute and chronic ( RQ = Exposure/Toxicity). RQs are then compared to EPA's levels of concern (LOCs). The LOCs are criteria used by the Agency to indicate potential risk to non

- target organisms. The criteria in dicate whether a pesticide, when used as directed, has the potential to cause adverse effects to non

- target organisms. To satisfy the data requirements for alpha

- cypermethrin, data were bridged between the registered racemic cypermethrin , and the register ed enriched isomeric mixture, zeta

cypermethrin. Based on similarities in the chemical properties and toxicological endpoints, environmental fate and ecotoxicity data are bridged between racemic cypermethrin and the enriched isomeric mixtures, as describe d in Appendix A of the risk assessment. A screening

- level risk assessment of the proposed uses suggests that alpha

cypermethrin presents potential risk to terrestrial mammals, freshwater fish, and invertebrates, and marine/estuarine fish and invertebrates

. In particular, the sensitivity of invertebrates to alpha

- cypermethrin are to be expected for a broad

- spectrum pyrethroid insecticide. However , EPA believes the risks associated with such effects are comparable to those risks associated with the already registered forms of cypermethrin including racemic cypermethrin and zeta

- cypermethrin. Furthermore, data specific for alpha

cypermethrin suggest that the persistence of the alpha enriched mixture is less persistent than that of zeta

- cypermethrin and race mic cypermethrin mixtures. Therefore, the environmental exposures used to assess these risks are likely to be overestimated for cases where exposure data was bridged from zeta

- cypermethrin and/or racemic cypermethrin.

I V
. RISK MANAGEMENT DECISION
EPA has concluded that the available data provide adequate information to make the determinations required by FIFRA Sec. 3(c)(5) with respect to alpha cypermethrin formulated as the manufacturing

- use product, BAS 3101 Technical Insecticide (Fastac Technica l) , and the end

- use product , BAS 310 401 (Fastac EC Insecticide)

. As required by FIFRA, the Agency published a notice of receipt (NOR) of the registration application in the Federal Register ( May 23, 2012 ). As required by FFDCA, the Agency published a not ice of filing (NOF) of the petition for pesticide tolerances in the Federal Register ( May 19, 2012 ). No comments were received in response to either the notice of receipt or notice of filing

. Additionally, on November 29 2012 , the Agency posted the proposed registration decision do c ument for alpha

- cypermethrin and supporting documents in to docket number EPA

- HQ

- OPP

- 2012

- 0185 for a 30

- day public comment period. N o comments were received.15 A . Labeling Requirements
In order to mitigate risks to non

- target plants and animals, EPA require s the label language to include directions intended to keep the pesticide on the treatment area, thereby reducing the potential for exposure of non

- target plants and animals. For example, spray drift management language would be required on the occupational/commercial labeling that advises users of applicator responsibilities and requires specific techniques to reduce the possibility of spray drift. In addition, surface and ground water advisori es would be required on all labeling, which may further reduce residues in drinking water and exposure of non

- target organisms. The product will be classified as a Restricted Use Pesticide, due to the risks to aquatic organisms. In order to mitigate co ncerns regarding exceedance of seasonal maximum usage rates for all forms of cypermethrin, including alpha

- cypermethrin along with other racemic cypermethrin and zeta

- cypermethrin products (registered by other companies), EPA has acquired labeling to restr ict the usage of alpha

- cypermethrin to crops that have not been treated previously with racemic cypermethrin or zeta

- cypermethrin. Tank mixing with other cypermethrin products have also been prohibited. Furthermore, the labeling prohibit s use of any other cypermethrin products on a crop within the same season if alpha

- cypermethrin is used on that same crop. This labeling will help to ensure that any usage of alpha

- cypermethrin replace s existing cypermethrin or zeta

cypermethrin usages, an d not add to total cypermethrin loading in the environment. Furthermore, because some applications of other forms of cypermethrin will be replaced by applications of a less persistent form, problematic environmental exposures can only decrease by the usa ge of alpha

- cypermethrin. This overall decrease in environmental loading is in the public interest.
B . Agency’s Final Regulatory Decision EPA has determined the following: 1) BASF Corporation has submitted satisfactory data to support the un condition al registration of the new active ingredient alpha

- cypermethrin, for use on alfalfa, brassica vegetables, citrus fruits, corn (field, pop, seed, and sweet), cotton, cucurbits, fruiting vegetables, leafy vegetables, legume vegetables, rice, root and tuber v egetables, sorghum, soybeans, sugar beets , tree nuts, and wheat, 2) the uses of alpha

- cypermethrin will not cause un reasonable adverse effects on the environment , and 3) that the registration of alpha

- cypermethrin will provide a net risk reduction with reg ard to overall use of the entire suite of registered cypermethrin products, as alpha

- cypermethrin wi ll provide the pesticide market

- place with a less persistent form of cypermethrin that (due to labeling), can only replace, and not add to, existing usage o f the already regis tered forms of cypermethrin. Furthermore, along with other cypermethrins, alpha

- cypermethrin is subject to EPA’s registration review program and will be evaluated in that context, simultaneously with zeta cypermethrin and cypermethrin

. Therefore , the Agency grant s this un con ditional registration.