UNITED STATES ENVIRONMENTAL PROTECTION AGE N CY WASHINGTON, D.C. 20460



### Date: September 10 , 2014 OFFICE OF CHEM CAL SAFETY AND POLLU T ION ,REVEN T ION



### Subject: Alpha-cypermethrin. Evaluati on of Two New Proposed Products fm Use in Commercia l /Res iden tial Settings. PC Code: 209600 Decision No.: 48 1 580 Petition No.: 3F88l89 Risk Assessment Type : Exposure Assessment TXR No .: NA MRIDNo.:NA


### From: Zaida Figueroa, Indus trial Hygienist Risk Assessment Branch II Health Effec ts Division (7509P) DP Barcode: 0414733 Registration No.: 499

- L TN, 199-LAO Regulatory Action: Section . · Case No .: NA CAS N o.: 67375-30-8 40 CFR: 180.418



### Through: Elizabeth Holman, Chemist



### ~ 

### ).1.L.___

To:

Introduction Ma rgarita Collantes, Biologist

**<pt~~**

**<- (2#~**  and Chr i st in a Swartz, Chief Ri s k Assessment Branch II Health Effec ts Division (7509P) Elizabeth Fertich!Kable Davis IVB 1 Branch Registration Division (7505P)

The Registration Division requ ested that th e Health Effects Divi sion (HED) co nduc t : . n exposure a

nd risk assessment for two proposed new products containing alpha-cypermethrin fo : control of various insects in commerc ial/residential (o utdoor /indoor) settings. This assessment :t ddresses commercial and residential handler and post-application exposure and risk resu lting 

### f om the proposed alpha

- cypermethrin products.
Page 

### 1 of8Table of Contents 1.0 Bac **ground** ............................. . .................................................................. .. .. .. .. .. .. .. .. ... . ... ... 3 2.0 H az trd C h aracterization ....................................................................................................... 3 3.0 Use Pr ofil e .......... . .. ... . ... . .. ...... .. .. . ... . .......................................................................... ... . . ... .. . 5 4.0 Res dent i a l Handler/Post - application Exposure and Ris k Estimates ................................... 6 5.0 Con 1 mercial Handler / P ost - application Exposure and Risk ........... . .. .. .. .. .. .. .. .. . ... .. .. .............. 8 6.0 Risl Assessment Concl u sions and R ecommendat i ons .................................... .. .. .. .. .. ... . ... .. . 8 6.1 S · a m mary of Risk Estimates .......... .. ......................................................... .. .. .. .. .. .............. 8 6.2 L L be l R e co mm e nda t ion s from Re s identi a l Assessment .......................... ........................ 8 Pag e 2 of8

### 1.0 Background A Section 3 registration was requested by BASF Corp oratio n on behalf of Whitmire 11icro-Gen Research Labora to ri es, Inc., for the use of two a lph a-cy permethrin products to contro insects outdoors/indoors in commercial, residential, food hand lin g establishments and institu ional settings . Alp ha-cypermethrin i s an enriched i somer of t h e pyrethroid ins ec ticide cyp( rmethrin , registered for both agricu ltural and residential uses. In addition, zeta-cypermethr in is also an enr iched i somer of cypermethrin. The toxicology database for the cypermethri n s incl1des studies with cypermethr in and both ofits enriched isomers, and is considered compie" e for the p urpose of risk assessment. The fi r st product , TC-327 (EPA File Symbol 499-LAO), is a read y-to-use (RTU) p re:' surized in secticide containing 0.05% alpha-cypermethrin as the so le acti ve in gredient, an d m : y be app li ed indoo rs/outdoors in to crack and crevices and as a spot (localized) and perime 1 er treatment. T hi s p roduct has the following addit ional brand names: PT® Fendon a Pres mrized Insecticide and P'flll Cy -Kick AC Pressurized In secticide. The second product, TC- 305 (EPA File Symbol 499- L TN), is a micro encapsul ated lie uid co ncentrate to be d i luted in water and contains 3
.0% alpha

- cypermethrin as the so le a :tive ingredient; the product may be applied indoors/outdoors into crack and crevice s and < 

### s a spot (localized) and perimeter treatment. This product h as the following ad ditio n al brand 1ames: Fendona TM CS In secticide and Cy-Kick® AC In secticide
. Based on the proposed use pattern , short-term ( 1-30 days) exposures are expected for commercial and resident ial handlers who apply the proposed products, as well as for ; . dults and children w h o may be exposed to previously treated areas (i.e
. , post-application). T his assessment addresses potential exposure and risk associated with the proposed p · oducts for alpha-c yp ermethrin when u sed as directed by commercial and residential handl ers.
2.0 

### Hazard Characterization The toxicologica l database for alpha-cypermethrin is complete (Midd leton, K., D376l t 98 , 8/ 11 / 2012). As stated above, alt ho ugh cypermethrin, a lpha- and zeta-cypermethrin 

### ru

**~separate** active ingredients with d ifferent end-use products, they are includ ed together in the h ; zard evaluation for the purpose of human health risk assessment. Cypermet hrin, zeta-cypermet hrin , and alpha-cypermethrin are structurally si mi lar Ty]te II pyrethroids, and like other pyrethroid s, cause neurotoxicity from interaction wi th so d urn c hannel s leadin g to clinical signs of neurotoxicity. Furthermore, rapid metaboli sm ar: d elimination prec lude accumulati on and increased potency fo llowing repeated do s ing. Several neuro toxic effects were seen in acute neurotoxicity (ACN) and subchronic neurotox icity (SCN) studies in rats with cypermethrin, zeta
- cypermethrin, and alpha-cypermethrin. C linic tl signs re lated to neurotoxi city were noted in all ACN studies for all three chemicals.
Page 

### 3 of8For a l pha-1 ypermethrin, clinical signs were mo s t frequently noted in rats do se d between 3 to 8 hours post· dosing. In SCN studies with the three chemicals, neurotoxic effects were observed at comparab l • **~** dos es. This is consistent with the t ox icity profiles for all t he pyrethroids which are marked by rap id a bsorption, metabolism , and time-to-peak effect. Fo r purposes of endpoint selection a 1d ex p osure assessment, only single day risk assessments need to be conducted.

Cyperm etl: t in, a lp ha- and zeta-cypermethrin exposu r e to children <6 years old is expected and it must be co 1side r e d in the context of the pyrethroids as a class. The FQPA UF of 3X for all pyrethroid: is considered adequately protecti ve fo r children <6 years of age. T he FQPA safety factor was : educ e d to 1 X for women of child bearing age (as well as for all adult populations and children> i yea rs ). The leve l c :f con c ern (LOC) for inhalation exposure and risk is 30 for adults and children 6 years

of age and )Ver, which includes an interspecie s f actor of 3X and intrasp ec ies factor of 1 OX. For childre n yc unge r than 6 years of age, the LOC i s 100 based on a 3X uncertainty factor to protect for exposu es to c hildren < 6 years of age based o n the increased quan t itative s usceptibility seen

in the scier t ific l i terature related to pyrethroid pharmacokinetic, an interspecies factor of 3X and intraspecie ; fact o r of 1 OX. The LOC for incidental oral exposure and ri sk i s 300 for children under 6 ye ; .rs of age, wh i ch includes a 3X uncertain ty factor retained t o account for the increa sed quantitativ

**susceptibil ty**  seen in the scientific literature relate d to py re throid pharmacokinetics , an interspe :ies f ac tor of 1 OX and intraspecies factor of 1 OX. No sys tem e eff ec t s were observed in the 21-day dermal rat study with ze ta-cypermethrin or cypermetlll in up t o the limit dose and there are no developmental or reproductive toxicity

concerns. f herefore , a dermal endpoint wa s not se lected , and there i s n o risk associated with exposure v a th e dermal route. A 21-day i :thala t ion study in rats was selected to assess short- and intermediate- term inhalation exposure. fhe NOAEL ofO.Ol mg / L was base d on decreased body weight and increased salivation< t the LOAEL of 0.05 m g/L. For occupat i ona l and residential inha l ation exposure , a human equ . valen t concentration (HEC) and hum an eq ui vale n t dose (HED) were derived in accordancE with st andard methodology that re s ult s in a reduction in the interspecies uncertainty factor (UF : from 1 OX to 3X. The H ED d ete rmin e d for the occupational inha la t ion risk assessment is 1. 10 mglkg / day; the HED i s 1.15 mg /kg/ da y for residential inhalation risk as sess ment :; . Fo r adults and children 6 years and o lder , the le v el of concern ( LOC) for inhalation expos ure a 1 d ri s k i s a margin of exposur e (M O E) of 30. For children you n ge r than 6 y ears of

age, t he LC Cis a n MOE of 100. The bencl111ark dose (BMD) methodo logy was used to determine the point of departure (POD)

for inciden al ora l exposure and ri sk assessment. The methods and assumptions used are described i 1 d etail in the aggregate risk assessm e nt for alpha-cypermethrin. The incidental oral benchmark dose leve l (BMDLtso) of7.16 mglkg was selected from an acute oral study in the rat , based on d • : crea s ed locomotor activity at the BMD va lue of 11.20 mglkg. For children under 6 years old , t 1e LOC for incidental oral expo s ure and risk i s an MOE of 300 . Page 4 of8The Agency has determined that the quantific ation of cancer risk using a non-l inear; : pproac h (i.e., RID) will adequately account for all chron ic toxicity, including carcinogenicity , which could res ult fro m exposure to cypennethrin
. No evidence of carcinogenicity was

**ob~** erved in carc inogenicity studies in rats with cypermethri n or in mice with alpha

- cypermethrin 

### 3
. 0 Use Profile Two new products are proposed to controls a variety of pests (e.g., cockroache s, hou: e flies , fi re /carpenter ants, ticks , crawling insects, bees, hornet , wasps , and other in sec ts): TC

- 327 (EPA File Symbol4 99-LAO) and TC-305 (EPA File Symbol499-LTN). The propo sed

**us**
**~** pattern s p ec ified on the end-use product labels is summarized below in Table 3.0. Tab l e 3.0. Summary of Directions for the Proposed End-Use Products for A lpba-cypermetbrir1 U

se Site/ Application Product/ Timing, Type, and Formulation Max. Single Applic. Rate Use Direct Equipment ms and Limitations Indo or/O utdoor- Co mm ercial , Residential a nd Food Handling Estab li s hmen 1 ; Crack & Crevice (Void) TC-327 treatment using injection tube 0.0033 lb ai/can @I IV/sec R esidual time using or tip. (EPA Reg. No. 499- days depen d ing on ! Spot application using RTU LAO) but no more than 2 t container
. Read y-to-use 0.0033 lb ai/can @ 2 tWsec must be at h.:ast 3 dr pressurized liquid supplied actuator, ir Perimeter application using (0.0 5% ai) 0.0033 lb ai/can @ 10 sec/s ite or BASF equipment. RTU container
. hole application rates is ua to 90 est s. Reapply as necessary. mes per week
. Appl ications y s apart . Use with the ection tubes/ tip o r o · her
Crack & Crev ice (Void) Residual time using treatment us ing injection
. tube 0.0033 lb ai/can @ I fW s cc or tip
. 30- 90 day s depend i neces sary. but no m Spot application using TC-305 Application s must 1:- injection tube or low pressure 0.0033 lb ai/can @ 2 tV/sec with equipment des i handheld equipment. EPA Reg
. No. 499- 1pplication rates range from 1g on pe s ts. Reapply as • re than 2 times per week. :at least 3 days ap art . Apply

**~ed** for void applications. LTN) Produ ct i s to be use• : as a re sidual /s upplemental Mi croenca psulated treatment. t:se high : r application rate to inhibit Perim eter. spot (spray) or liquid concent rate wood-inf est i ng in se• (3.0% ai) expo sed tubing , era• : general surface app l ication (0.25 lb a i/ gal) 0.0039-0.00 59 lb ai/ gal substitute for other 1 using low pressu r e handheld (20-30 11 ozll0 gal) General su rf ace app equipment. when the facility is t sand termite infestz.tions in ks or cold joints

**(thi~** is not a :rmite treatments). ications for FHE may be u sed 1 ot in o peratio n and f)od/feed has been co v ered or : emoved from the application area. Lawns/O rnamental s TC-305 Not for u sc 111 comn Perimeter (s pra y) applic ation Microencapsulated 0.00012 lb ai/gal (o rnamental s) nurseries. To be use using backpack sprayer or liquid concentrate 0.0 1 lb ai / A (turf) greenhouse. interior handheld equipment. (3.0% ai) Residual T ime = 30 (0.25 lb ai/gal) · !rcial greenhouses o r

. in golf courses. hobby capes, landscapes and lawns
.

· X> days d e pending 0 : 1 pe s t. Livestock Ho u s in g

Page 5 of8Table 3.0.

**~** Use Site/ Timing, Equ

. ummary of Directions for the Proposed End-Use Products for Alpha-cypermethrin. Peri meter ( sp

u si n g backpa1 handheld equ

\ pplic a tion Type, andpment a y) a ppl ication k spray e r o r p ment.

Product/ Formulation TC-305 M icrocncaps ulated liquid concentrate (3 . 0% a i ) ( 0 . 25 lb ai / gal )

Max. Single Applic. Rate Use Directions and Limitations 0.0085 l b a i / A T o be use in and on out si de su rf ace s of ou t er ( 1. 0 n o z/ 1 , 000 IV) building . T r eat a band of6-10 ft around / adjacen t 0 . 44 lb ai / A (5.0 fl oz/1 , 000 ttl to th e bui l ding. Use higher app l ication rate to for darklin g beetles onl y ) c o nt r ol darkling beetles onl v. 4.0 Re1 :idential Handler/Post-application Expos ure and Risk Estimates Based on t l L e proposed use pattern for both product s, the exposed individuals will be adult residential 1andl e rs who apply the ready-to

- u se product, as well as adults and children that are

exposed to t reated areas. Since no dermal endpoint of concern was identified, residential assessmen t 3 for alpha-cypermethrin are based on inhalation and incidental oral (for children) ex po s ures • mly. Nume rous 10n-o ccupational/resi den t ial handler exposure assessments for the use of zetacy permethJ in and cypermethrin have been previously conducted in support of new uses and reregistrati m (M . Colla nt es, December 4, 2001 , 0279002; S . Wang , July 1 6, 20 06 , 03 1 2472 and March 30, W07 0 337823 ; S. Tadayon, 0293417 and 0293417, AprilS , 2006). In 2012, the Revised Ot cupat i onal and Residential Exposure Assessment for the R e r eg istered Eligibility Decision I: o cument ( RED) , 2011 P yrethroid C umulati v e Risk (PCR) Assessment (0394576) Appendix : nd various r eg i stered labels were u se d to capture and summarize the most conservat i ' e residen t ial handler sce nari os for the cypermet hrin s . Representa .ive outdoor and indoor residential handler expos ure sce nario s were reassessed for all cypermetlu i ns us i ng the Revised Residential SOPs (20 12) , and t he ris k estimates were not of concern (C .> ll ant e s , M .; D40360 1 ; 8 / 4/20 1 2) . T h e est imated inhalation MOEs for handler expos ure n nged f rom 6,1 00-48,000 (LOC = 30). Inhalation handler exposure from mixin g/ loa l ing and app l ying cypermethrin using a backpack sp r ayer for a turf treatment resulted in the wors . case e xposure estimates for r esidential adults (MOE=6, 1 0 0 ) . Post-appliotion adult and c hildren 's inhalation and incidental oral (chi ldr e n only) exposure resulting fr >m indoor and outdoor uses were a l so rea ss essed (Collant es, M.; 0403601; 8 / 4 / 20 12) and were n )t of concern. T h e adult and children 's po s t-application inhalation MOEs resultin g from indo o: · uses rang ed from 250,000-1,000 , 000 (LOCactu lt=30; L0C c hilct = 100). T he MOEs for incidental < ral post-application exposure for chi l dren (1 to < 2 years old) ran ge d from 1,000-

200,000. 1 he in d oor fogger use resulted in the worst case highest incidental oral postapplication expo s ure estimate (MOE = l , OOO ; LOC =3 00). Based on t] . e propo se d u se pattern , application rat es and treatment directi o n s (e.g., cracks and c revices , S J ot or p e rim e t e r applications near infested egg la y ing sites, harbora ges or Page 6 of8forage/feed ing areas 1 ; outdoor spot, perimeter and spray treatments) , the expo s ures t )r the proposed products are expected to be lowe r than those of other currently regi stered 1 roducts containing alpha-cypermethrin tha t are used in res idential sett ings for outdoor (e.g. , awns) and indoor (e.g., fogger) broadcas t treatments. As a re s ult , the residential ri sk estimates for the proposed produc ts wou ld be expec t( d to result in less exposure than those previously assessed , w hi ch wer e not of concern (Collantes , 

### \11. ; 0 403601 ; 8/4/ 2012 )
. Consequently , the previous residential exposure assessments f >r the cypermethr ins are expected to be protective of expos ure expected to resu lt from the 1 • rop osed products/uses. Therefore , HED did not quantitativ ely assess re si d ential handl er and )OStapplic atio n exposures for the proposed TC

- 327 (EPA Fi le Symbol 499-LAO) and T< : - 305 (EPA File Symbol 499-L TN) products. Res ident ia l Risk Estimat es and Expo s ure Scenario for Aggregate Assessment The a ggregate ri sk assessment fo r alpha-cypermethrin mu st co nsider potenti al expos Ire from all cyp ermethrins (i.e. , cypermethrin and zeta-cypermethrin) , since the 3 ac ti ve ingredie 1 ts are considered to be essentially the same active from the mammalian toxicity persp ectivt : . The combined residential adult h and ler and ch ildren ' s scenarios previously assessed by I- ED still represent the worst case exposure for each li fe stage and thus are protective of a ll otl e r residential uses (Collantes , M. ; 0403 60 1 ; 8/4/20 1 2) ; proposed and ex i sting uses resl : l t in risk esatimates that are not of concern. Cumulative Risk Assessment The Agency is required to cons ider the cum ul at ive risks of chemicals sharing a cornr ton mechanism oftoxicity. The Agency has determined that the pyrethroids and pyrethr : ns share a common m ec hani sm oftoxicity (http: // www.regu lations.gov ; EPA-HQ-OPP-2 008

- 0 ·

**89 -0006).**  The members of thi s gro up share the ability to interact with voltage

- gated sodium ch
. mnel s ultimately leading t o neurotoxicity. The cumul ative ri sk assessment for the pyrethro :ds/ pyrethr ins was publis he d on 1119 /2 011 and i s avai lab le at http:/ /www.regu lations.go , ; EPA-HQ

OPP-2011-0746. No cumul ative ri sks of con ce rn were identified , all owing the Agen ;y to con sider new u ses for pyrethroids. For information regarding EP A ' s efforts to eval u ; t te the ri sk of exposure to thi s c lass of chemical s, refer to: http: // www.epa.gov/oppsrrd 1 /reevaluation/pyrethroids-pyrethrins.htm l. Cypermethrin and z eta
- cypermethrin res idential uses are included in the pyrethroid /p r rethrin cumul a tiv e risk assessment (CRA). The proposed us e ha s an in significant imp act on t he cumul ative risk assess m ent. No dietary , residential , or aggregate risk es timate s of co 1 cern have been identified in the single c hemical as sessment. In the cumulative assessment , res i i ential exposure was the greatest co ntributor to the tota l exposure. Althou gh there are resid< : ntial uses for cype rmet hrin and zeta
- cypermet hrin , the exp osures for the proposed products are expecte d to be lower than those of other currently registered products containing a lpha- cyp erme tl lfin that are used in res idential s ettings for out d oor (e.g. , lawns) and indoor ( e .g. , fogger) broadca ; t
1 Exampl es of location s inc lude hollow spac es in floo rs , wall s , ce ilin gs; c racks and crevices around pij1es , do ors, windo ws , re frigerat ors , s toves ; b ehind or und er baseboard s , c upboard s , c abinets , etc . Page 7 of8treatments. Ther efore, the proposed use will have no impact on the residential component of the cumulative risk estima tes. 5 . 0 Cot :tmercial Hand l er/Post-application Exposure and Risk Commerci< I han d ler exposure is also expected for individuals applying TC-327 and TC-305 insecticide )roducts in indoor re side ntial , institu t ional and commercial facilities. Numerous commercia hand l er ex posu re assessments for the use of zeta -cypermethrin , cypermethrin and alpha-cype methrin are available, and in dicate there are no risks of concern for commercia /occupationa l handlers (Collantes, M ., D279002, 12/4/2001; Wang, S . , D312472, 7/16 / 2006; Wang , S., D337823, 3/30/2007; Tadayon , S., D293417, 4 / 5/2006). Cypermethrin and zeta-C) p ermethrin commercial handl er scenarios resulted in inhalation risk estimates greater tha 1 . their respective LOCs, with MOEs ranging from 2,700 to 160,000 (Tadayon, S., D293417,**~** /5/2006). Based on the application rates and directions, the proposed products will result in lo · ve r exposure than the exposure from the currently registered cypermethrin and zetacypermetru i n products. The risk estimates calculated for cypermethrin and zeta-cypermethrin are conside r ed protective of commercial handler exposures resulting from the proposed a lphacypermetru i .n commercial/occupational use s. Furthermo1 e, ba se d on the use -pattern associated with the proposed products , HED believes the presence o l commercial handlers in treated areas is minimal after application; therefore , pos t application exposure and risk for these wor kers are expected to be negligible. 6.0 Ris · (Assessment Conclusions and Recommendations 6.1 Sm1mary of Risk Estimates The expos\ re an d risk estimates for the proposed alpha-cypermethrin products are not expected

to be great1 r than the exposure and risk es timates for the curren t ly registered products assessed in the prev : ous o c cupational/residential exposure (Collantes, M., D403601, 8/4 / 2012) and human health/agg1 : !gate assessmen t for this chemical (Middleton, K., D376098, 811112012). As a result, a new quar t itativ e assessment i s not required at this time , and the re are no risks of concern expected v. t th th e proposed uses. 6 . 2**Lal el**  Recommendations from Residentia l Assessment None. Page 8 of8