UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

Date: September 10, 2014 

OFFICE OF CHEM CAL SAFETY 

AND POLLUTION ,REVENTION 

Subject: Alpha-cypermethrin. Evaluation of Two New Proposed Products fm Use in 

Commercial/Residential Settings. 

PC Code: 209600 

Decision No.: 48 1580 

Petition No.: 3F88l89 

Risk Assessment Type: Exposure Assessment 

TXR No.: NA 

MRIDNo.:NA 

From: Zaida Figueroa, Industrial Hygienist 

Risk Assessment Branch II 

Health Effects Division (7509P) 

DP Barcode: 0414733 

Registration No.: 499-L TN, 199-LAO 

Regulatory Action: Section . · 

Case No.: NA 

CAS No.: 67375-30-8 

40 CFR: 180.418 

Through: Elizabeth Holman, Chemist ~ ).1.L.___ 

To: 

Introduction 

Margarita Collantes, Biologist <pt~~<- (2#~ 

and 

Christina Swartz, Chief 

Risk Assessment Branch II 

Health Effects Division (7509P) 

Elizabeth Fertich!Kable Davis 

IVB 1 Branch 

Registration Division (7505P) 

The Registration Division requested that the Health Effects Division (HED) conduct : .n exposure 

and risk assessment for two proposed new products containing alpha-cypermethrin fo : control of 

various insects in commercial/residential (outdoor/indoor) settings. This assessment : tddresses 

commercial and residential handler and post-application exposure and risk resulting f om the 

proposed alpha-cypermethrin products. 

Page 1 of8 
Table of Contents 

1.0 Bac ground .................................................................................................. .... .... .... ..... .... ... 3 

2.0 Haz trd Characterization ....................................................................................................... 3 

3.0 Use Profile ........................................................................................................................... 5 

4.0 Res dential Handler/Post-application Exposure and Risk Estimates ................................... 6 

5.0 Con 1mercial Handler/Post-application Exposure and Risk ................ .................................. 8 

6.0 Risl Assessment Conclusions and Recommendations ........................................................ 8 

6.1 S· am mary of Risk Estimates ............................................................................................. 8 

6.2 L Lbel Recommendations from Residential Assessment .................................................. 8 

Page 2 of8 
1.0 Background 

A Section 3 registration was requested by BASF Corporation on behalf of Whitmire 1 1icro-Gen 

Research Laboratories, Inc., for the use of two alpha-cypermethrin products to contro insects 

outdoors/indoors in commercial, residential, food handling establishments and institu ional 

settings. Alpha-cypermethrin is an enriched isomer of the pyrethroid insecticide cyp( rmethrin, 

registered for both agricultural and residential uses. In addition, zeta-cypermethrin is also an 

enriched isomer of cypermethrin. The toxicology database for the cypermethrins incl1des 

studies with cypermethrin and both of its enriched isomers, and is considered com pie" e for the 

purpose of risk assessment. 

The first product, TC-327 (EPA File Symbol 499-LAO), is a ready-to-use (RTU) pre:' surized 

insecticide containing 0.05% alpha-cypermethrin as the sole active ingredient, and m: y be 

applied indoors/outdoors into crack and crevices and as a spot (localized) and perime1 er 

treatment. This product has the following additional brand names: PT® Fendona Pres mrized 

Insecticide and P'flll Cy-Kick AC Pressurized Insecticide. 

The second product, TC-305 (EPA File Symbol 499-L TN), is a microencapsulated lie uid 

concentrate to be diluted in water and contains 3.0% alpha-cypermethrin as the sole a :tive 

ingredient; the product may be applied indoors/outdoors into crack and crevices and < s a spot 

(localized) and perimeter treatment. This product has the following additional brand 1ames: 

Fendona TM CS Insecticide and Cy-Kick® AC Insecticide. 

Based on the proposed use pattern, short-term ( 1-30 days) exposures are expected for 

commercial and residential handlers who apply the proposed products, as well as for ; .dults and 

children who may be exposed to previously treated areas (i.e., post-application). 

This assessment addresses potential exposure and risk associated with the proposed p ·oducts for 

alpha-cypermethrin when used as directed by commercial and residential handlers. 

2.0 Hazard Characterization 

The toxicological database for alpha-cypermethrin is complete (Middleton, K., D376l t98, 

8/11/2012). As stated above, although cypermethrin, alpha- and zeta-cypermethrin ru ~separate 

active ingredients with different end-use products, they are included together in the h; zard 

evaluation for the purpose of human health risk assessment. 

Cypermethrin, zeta-cypermethrin, and alpha-cypermethrin are structurally similar Ty] te II 

pyrethroids, and like other pyrethroids, cause neurotoxicity from interaction with sod urn 

channels leading to clinical signs of neurotoxicity. Furthermore, rapid metabolism ar: d 

elimination preclude accumulation and increased potency following repeated dosing. Several 

neurotoxic effects were seen in acute neurotoxicity (ACN) and subchronic neurotoxicity (SCN) 

studies in rats with cypermethrin, zeta-cypermethrin, and alpha-cypermethrin. Clinic tl signs 

related to neurotoxicity were noted in all ACN studies for all three chemicals. 

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For alpha-1 ypermethrin, clinical signs were most frequently noted in rats dosed between 3 to 8 

hours post· dosing. In SCN studies with the three chemicals, neurotoxic effects were observed at 

comparabl• ~ doses. This is consistent with the toxicity profiles for all the pyrethroids which are 

marked by rapid absorption, metabolism, and time-to-peak effect. For purposes of endpoint 

selection a 1d exposure assessment, only single day risk assessments need to be conducted. 

Cypermetl: tin, alpha- and zeta-cypermethrin exposure to children <6 years old is expected and it 

must be co 1sidered in the context of the pyrethroids as a class. The FQPA UF of 3X for all 

pyrethroid: is considered adequately protective for children <6 years of age. The FQPA safety 

factor was :educed to 1 X for women of child bearing age (as well as for all adult populations and 

children> i years). 

The level c :f concern (LOC) for inhalation exposure and risk is 30 for adults and children 6 years 

of age and )Ver, which includes an interspecies factor of 3X and intraspecies factor of 1 OX. For 

children yc unger than 6 years of age, the LOC is 100 based on a 3X uncertainty factor to protect 

for exposu es to children <6 years of age based on the increased quantitative susceptibility seen 

in the scier tific literature related to pyrethroid pharmacokinetic, an interspecies factor of 3X and 

intraspecie ; factor of 1 OX. The LOC for incidental oral exposure and risk is 300 for children 

under 6 ye; .rs of age, which includes a 3X uncertainty factor retained to account for the increased 

quantitativ susceptibil ty seen in the scientific literature related to pyrethroid pharmacokinetics, 

an interspe :ies factor of 1 OX and intraspecies factor of 1 OX. 

No system e effects were observed in the 21-day dermal rat study with zeta-cypermethrin or 

cypermetlll in up to the limit dose and there are no developmental or reproductive toxicity 

concerns. fherefore, a dermal endpoint was not selected, and there is no risk associated with 

exposure v a the dermal route. 

A 21-day i :thalation study in rats was selected to assess short- and intermediate- term inhalation 

exposure. fhe NOAEL ofO.Ol mg/L was based on decreased body weight and increased 

salivation< t the LOAEL of 0.05 mg/L. For occupational and residential inhalation exposure, a 

human equ .valent concentration (HEC) and human equivalent dose (HED) were derived in 

accordancE with standard methodology that results in a reduction in the interspecies uncertainty 

factor (UF: from 1 OX to 3X. The HED determined for the occupational inhalation risk 

assessment is 1.10 mglkg/day; the HED is 1.15 mg/kg/day for residential inhalation risk 

assessment :;. For adults and children 6 years and older, the level of concern (LOC) for inhalation 

exposure a 1d risk is a margin of exposure (MOE) of 30. For children younger than 6 years of 

age, the LC Cis an MOE of 100. 

The bencl111ark dose (BMD) methodology was used to determine the point of departure (POD) 

for inciden al oral exposure and risk assessment. The methods and assumptions used are 

described i 1 detail in the aggregate risk assessment for alpha-cypermethrin. The incidental oral 

benchmark dose level (BMDLtso) of7.16 mglkg was selected from an acute oral study in the rat, 

based on d• :creased locomotor activity at the BMD value of 11.20 mglkg. For children under 6 

years old, t 1e LOC for incidental oral exposure and risk is an MOE of 300. 

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The Agency has determined that the quantification of cancer risk using a non-linear;: pproach 

(i.e., RID) will adequately account for all chronic toxicity, including carcinogenicity, which 

could result from exposure to cypennethrin. No evidence of carcinogenicity was ob~ erved in 

carcinogenicity studies in rats with cypermethrin or in mice with alpha-cypermethrin 

3.0 Use Profile 

Two new products are proposed to controls a variety of pests (e.g., cockroaches, hou: e flies, 

fire/carpenter ants, ticks, crawling insects, bees, hornet, wasps, and other insects): TC -327 (EPA 

File Symbol499-LAO) and TC-305 (EPA File Symbol499-LTN). The proposed us~ pattern 

specified on the end-use product labels is summarized below in Table 3.0. 

Table 3.0. Summary of Directions for the Proposed End-Use Products for Alpba-cypermetbrir1 

Use Site/ Application Product/ Timing, Type, and Formulation Max. Single Applic. Rate Use Direct 

Equipment 

ms and Limitations 

Indoor/Outdoor- Commercial, Residential and Food Handling Establishmen1 ; 

Crack & Crevice (Void) TC-327 treatment using injection tube 0.0033 lb ai/can @I IV/sec Residual time using 

or tip. (EPA Reg. No. 499- days depending on ! 

Spot application using RTU LAO) but no more than 2 t 

container. Ready-to-use 0.0033 lb ai/can @ 2 tWsec must be at h.:ast 3 dr 

pressurized liquid supplied actuator, ir 

Perimeter application using (0.05% ai) 0.0033 lb ai/can @ 10 sec/site or BASF equipment. RTU container. hole 

application rates is ua to 90 

ests. Reapply as necessary. 

mes per week. Applications 

ys apart. Use with the 

ection tubes/tip or o·her 

Crack & Crevice (Void) 

treatment us Residual time using ing injection. tube 0.0033 lb ai/can @ I fWscc 

or tip. 30- 90 days dependi 

necessary. but no m Spot application using 

TC-305 Applications must 1:- injection tube or low pressure 0.0033 lb ai/can @ 2 tV/sec with equipment desi handheld equipment. EPA Reg. No. 499-

1pplication rates range from 

1g on pests. Reapply as 

•re than 2 times per week. 

:at least 3 days apart. Apply 

~ed for void applications. 

LTN) Product is to be use•: as a residual/supplemental 

Microencapsulated treatment. t:se high: r application rate to inhibit 

Perimeter. spot (spray) or liquid concentrate wood-infesting inse• 

(3.0% ai) exposed tubing, era•: general surface application (0.25 lb ai/gal) 

0.0039-0.0059 lb ai/gal substitute for other 1 using low pressure handheld (20-30 11 ozll 0 gal) 

equipment. General surface app 

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 used 

1 ot in operation and f)od/feed 

has been covered or :emoved from the application 

area. 

Lawns/Ornamentals 

TC-305 

Not for usc 111 comn Perimeter (spray) application Microencapsulated 0.00012 lb ai/gal (ornamentals) nurseries. To be use using backpack sprayer or liquid concentrate 

0.01 lb ai/A (turf) greenhouse. interior handheld equipment. (3.0% ai) 

Residual Time = 30 (0.25 lb ai/gal) 

· !rcial greenhouses or 

. in golf courses. hobby 

capes, landscapes and lawns. 

·X> days depending 0:1 pest. 

Livestock Housing 

Page 5 of8 
Table 3.0. ~ 

Use Site/ 

Timing, 

Equ 

.ummary of Directions for the Proposed End-Use Products for Alpha-cypermethrin. 

Peri meter ( sp 

using backpa1 

handheld equ 

\ pplication 

Type, and 

pment 

ay) appl ication 

k sprayer or 

pment. 

Product/ 

Formulation 

TC-305 

M icrocncapsulated 

liquid concentrate 

(3 .0% ai) 

(0.25 lb ai/gal) 

Max. Single Applic. Rate Use Directions and Limitations 

0.0085 lb ai/A To be use in and on outside surfaces of outer 

( 1.0 n oz/ 1,000 IV) building. Treat a band of6-10 ft around/adjacent 

0.44 lb ai/A (5.0 fl oz/1 ,000 ttl to the building. Use higher application rate to 

for darkling beetles only) control darkling beetles onlv. 

4.0 Re1 :idential Handler/Post-application Exposure and Risk Estimates 

Based on tl Le proposed use pattern for both products, the exposed individuals will be adult 

residential 1andlers who apply the ready-to-use product, as well as adults and children that are 

exposed to treated areas. Since no dermal endpoint of concern was identified, residential 

assessment 3 for alpha-cypermethrin are based on inhalation and incidental oral (for children) 

exposures •mly. 

Numerous 10n-occupational/residential handler exposure assessments for the use of zetacypermethJ in and cypermethrin have been previously conducted in support of new uses and 

reregistrati m (M. Collantes, December 4, 2001 , 0279002; S. Wang, July 16, 2006, 03 12472 and 

March 30, W070 337823; S. Tadayon, 0293417 and 0293417, AprilS, 2006). In 2012, the 

Revised Ot cupational and Residential Exposure Assessment for the Reregistered Eligibility 

Decision I: ocument (RED), 2011 Pyrethroid Cumulative Risk (PCR) Assessment (0394576) 

Appendix : nd various registered labels were used to capture and summarize the most 

conservati' e residential handler scenarios for the cypermethrins. 

Representa .ive outdoor and indoor residential handler exposure scenarios were reassessed for all 

cypermetlu ins using the Revised Residential SOPs (20 12), and the risk estimates were not of 

concern (C .>llantes, M.; D40360 1; 8/4/20 12). The estimated inhalation MOEs for handler 

exposure n nged from 6,1 00-48,000 (LOC=30). Inhalation handler exposure from 

mixing/loa ling and applying cypermethrin using a backpack sprayer for a turf treatment resulted 

in the wors. case exposure estimates for residential adults (MOE=6, 1 00). 

Post-appliotion adult and children's inhalation and incidental oral (children only) exposure 

resulting fr >m indoor and outdoor uses were also reassessed (Collantes, M.; 0403601; 8/4/20 12) 

and were n )t of concern. The adult and children's post-application inhalation MOEs resulting 

from indoo:· uses ranged from 250,000-1,000,000 (LOCactult=30; L0Cchilct=100). The MOEs for 

incidental < ral post-application exposure for children (1 to < 2 years old) ranged from 1,000-

200,000. 1 he indoor fogger use resulted in the worst case highest incidental oral postapplication exposure estimate (MOE= l,OOO; LOC=300). 

Based on t] .e proposed use pattern, application rates and treatment directions (e.g., cracks and 

crevices, SJ ot or perimeter applications near infested egg laying sites, harborages or 

Page 6 of8 
forage/feeding areas 1

; outdoor spot, perimeter and spray treatments), the exposures t )r the 

proposed products are expected to be lower than those of other currently registered 1 roducts 

containing alpha-cypermethrin that are used in residential settings for outdoor (e.g., awns) and 

indoor (e.g., fogger) broadcast treatments. 

As a result, the residential risk estimates for the proposed products would be expect( d to result in 

less exposure than those previously assessed, which were not of concern (Collantes, \11.; 

0 403601 ; 8/4/2012). Consequently, the previous residential exposure assessments f >r the 

cypermethrins are expected to be protective of exposure expected to result from the 1 •roposed 

products/uses. Therefore, HED did not quantitatively assess residential handler and )OStapplication exposures for the proposed TC-327 (EPA File Symbol 499-LAO) and T< :-305 (EPA 

File Symbol 499-L TN) products. 

Residential Risk Estimates and Exposure Scenario for Aggregate Assessment 

The aggregate risk assessment for alpha-cypermethrin must consider potential expos Ire from all 

cypermethrins (i.e., cypermethrin and zeta-cypermethrin), since the 3 active ingredie 1ts are 

considered to be essentially the same active from the mammalian toxicity perspectivt :. The 

combined residential adult handler and children's scenarios previously assessed by I- ED still 

represent the worst case exposure for each life stage and thus are protective of all otl er 

residential uses (Collantes, M.; 0403601; 8/4/20 12); proposed and existing uses resl:lt in risk 

esatimates that are not of concern. 

Cumulative Risk Assessment 

The Agency is required to consider the cumulative risks of chemicals sharing a cornr ton 

mechanism of toxicity. The Agency has determined that the pyrethroids and pyrethr: ns share a 

common mechanism of toxicity (http://www.regulations.gov; EPA-HQ-OPP-2008-0· 89-0006). 

The members of this group share the ability to interact with voltage-gated sodium ch. mnels 

ultimately leading to neurotoxicity. The cumulative risk assessment for the pyrethro: ds/ 

pyrethrins was published on 1119/2011 and is available at http://www.regulations.go, ; EPA-HQOPP-2011-0746. No cumulative risks of concern were identified, allowing the Agen ;y to 

consider new uses for pyrethroids. For information regarding EPA's efforts to evalu; tte the risk 

of exposure to this class of chemicals, refer to: 

http://www.epa.gov/oppsrrd 1/reevaluation/pyrethroids-pyrethrins.html. 

Cypermethrin and zeta-cypermethrin residential uses are included in the pyrethroid/p rrethrin 

cumulative risk assessment (CRA). The proposed use has an insignificant impact on the 

cumulative risk assessment. No dietary, residential, or aggregate risk estimates of co 1cern have 

been identified in the single chemical assessment. In the cumulative assessment, resi iential 

exposure was the greatest contributor to the total exposure. Although there are resid<: ntial uses 

for cypermethrin and zeta-cypermethrin, the exposures for the proposed products are expected to 

be lower than those of other currently registered products containing alpha-cypermetl lfin that are 

used in residential settings for outdoor (e.g., lawns) and indoor (e.g., fogger) broadca ;t 

1 Examples of locations include hollow spaces in floors, walls, ceilings; cracks and crevices around pij1es, doors, 

windows, refrigerators, stoves; behind or under baseboards, cupboards, cabinets, etc. 

Page 7 of8 
treatments. Therefore, the proposed use will have no impact on the residential component of the 

cumulative risk estimates. 

5.0 Cot :tmercial Handler/Post-application Exposure and Risk 

Commerci< I handler exposure is also expected for individuals applying TC-327 and TC-305 

insecticide )roducts in indoor residential, institutional and commercial facilities. Numerous 

commercia handler exposure assessments for the use of zeta-cypermethrin, cypermethrin and 

alpha-cype methrin are available, and indicate there are no risks of concern for 

commercia /occupational 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) permethrin commercial handler scenarios resulted in inhalation risk estimates 

greater tha1. 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· ver exposure than the exposure from the currently registered cypermethrin and zetacypermetru in products. The risk estimates calculated for cypermethrin and zeta-cypermethrin 

are conside red protective of commercial handler exposures resulting from the proposed alphacypermetru i.n commercial/occupational uses. 

Furthermo1 e, based on the use-pattern associated with the proposed products, HED believes the 

presence ol commercial handlers in treated areas is minimal after application; therefore, postapplication exposure and risk for these workers are expected to be negligible. 

6.0 Ris ·(Assessment Conclusions and Recommendations 

6.1 Sm1mary of Risk Estimates 

The expos\ re and risk estimates for the proposed alpha-cypermethrin products are not expected 

to be great1 r than the exposure and risk estimates for the currently registered products assessed 

in the prev:ous occupational/residential exposure (Collantes, M., D403601, 8/4/2012) and human 

health/agg1 :!gate assessment for this chemical (Middleton, K., D376098, 811112012). As a result, 

a new quar titative assessment is not required at this time, and there are no risks of concern 

expected v. tth the proposed uses. 

6.2 Lal el Recommendations from Residential Assessment 

None. 

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