UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

Date: October 28, 2014 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

SUBJECT: Alpha-Cypermethrin -Human Health Risk Assessment for Two New 

Proposed Products for Use in Commercial/Residential Settings. 

PC Code: 209600 

Decision No.: 481579 

Petition No.: 3F88189 

Assessment Type: Single 

Chemical/ Aggregate 

TXRNo.: NA 

MRID Nos.: See Bibliography 

DP Barcode: D414726 

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

Regulatory Action: Section 3 

Registration Case No.: NA 

CAS No.: 67375-30-8 

40 CFR: 180.418 

FROM: Elizabeth Holman, Physical Scientist/Ri~sk s ssor ~ l~ 

Zaida Figueroa, Industrial HygienisL 

Karlyn Middleton, Toxicologist 1 ..... Risk Assessment Branch II 

Health Effects Division (7509P) 

THROUGH: Christina Swartz, Branch Chief 

Risk Assessment Branch II 

Health Effects Division (7509P) 

TO: Elizabeth Fertich/Kable Davis 

IVB 1 Branch 

Registration Division (7505P) 

Page 1 of8 
1.0 Executive Summary 

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

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

outdoors/indoors in commercial, residential, food handling establishments and institutional 

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

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

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

studies with cypermethrin and both of its enriched isomers, and is considered complete for the 

purpose of risk assessment. 

The first product, TC-327 (EPA File Symbol499-LAO), is a ready-to-use (RTU) pressurized 

insecticide containing 0.05% alpha-cypermethrin as the sole active ingredient, and may be 

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

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

Insecticide and PT® Cy-Kick AC Pressurized Insecticide. 

The second product, TC-305 (EPA File Symbol499-LTN), is a microencapsulated liquid 

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

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

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

FendonaTM CS Insecticide and Cy-Kick® AC Insecticide. 

The toxicological database for alpha-cypermethrin is complete (Middleton, K., D376098, 

8/1112012). As stated above, although cypermethrin, alpha- and zeta-cypermethrin are separate 

active ingredients with different end-use products, they are included together in the hazard 

evaluation for the purpose of human health risk assessment. 

Cypermethrin, zeta-cypermethrin, and alpha-cypermethrin are structurally similar Type II 

pyrethroids, and like other pyrethroids, cause neurotoxicity from interaction with sodium 

channels leading to clinical signs of neurotoxicity. Furthermore, rapid metabolism and 

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. Clinical signs 

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

For alpha-cypermethrin, 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 

comparable 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 and exposure assessment, only single day risk assessments need to be conducted. 

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

must be considered in the context of the pyrethroids as a class. The FQP A UF of 3X for all 

pyrethroids is considered adequately protective for children <6 years of age. The FQP A safety 

Page 2 of8 
factor was reduced to 1 X for women of child bearing age (as well as for all adult populations and 

children> 6 years). 

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

of age and over, which includes an interspecies factor of3X and intraspecies factor of lOX. For 

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

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

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

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

under 6 years of age, which includes a 3X uncertainty factor retained to account for the increased 

quantitative susceptibility seen in the scientific literature related to pyrethroid pharmacokinetics, 

an interspecies factor of 1 OX and intraspecies factor of 1 OX. 

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

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

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

exposure via the dermal route. 

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

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

salivation at the LOAEL of 0.05 mg!L. For occupational and residential inhalation exposure, a 

human equivalent 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 mg/kg/day; the HED is 1.15 mg/kg/day for residential inhalation risk 

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

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

age, the LOC is an MOE of 100. Since this hazard characterization was completed, RED's 

approach for calculating HEC's has evolved which would result in slight changes in the points of 

departure for inhalation risk assessment for the cypermethrins. However, these slight changes 

will not affect the risk assessment (i.e. the current estimated MOEs are protective). 

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

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

described in detail in the aggregate risk assessment for alpha-cypermethrin. The dose used for 

risk assessment was determined using a benchmark dose (BMD) analysis using 1 standard 

deviation (BMDLtso) from the control group as the benchmark response (BMR) as suggested for 

continuous endpoints in the Agency's BMD guidance (USEPA 2012). The incidental oral 

benchmark dose level (BMDL1so) of7.16 mg/kg was selected from an acute oral study in the rat, 

based on decreased locomotor activity at the BMD value of 11.20 mg/kg. For children under 6 

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

The Agency has determined that the quantification of cancer risk using a non-linear approach 

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

could result from exposure to cypermethrin. No evidence of carcinogenicity was observed in 

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

Page 3 of8 
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 adults and 

children who may be exposed to previously treated areas (i.e., post-application). Since no 

dermal endpoint of concern was identified, residential assessments for alpha-cypermethrin are 

based on inhalation and incidental oral (for children) exposures only. These proposed new uses 

were compared against the existing use pattern in a recent occupational and residential exposure 

assessment (D414733, Z. Figueroa, 9/10/2014). Based on application rates and treatment 

directions (e.g., cracks and crevices, spot or perimeter applications near infested egg laying sites, 

harborages or forage/feeding areas 1

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

for the proposed products are expected to be lower than those of other currently registered 

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

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

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

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

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

combined residential adult handler and children's scenarios previously assessed by HED still 

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

residential uses (Collantes, M.; D403601; 8/4/2012); proposed and existing uses result in risk 

esatimates that are not of concern. 

The proposed tolerances associated with the food handling establishment (FHE) use of alphacypermethrin are identical to those currently established for zeta-cypermethrin. Based on the 

available alpha-cypermethrin residue data submitted for this new use petition, this FHE use will 

not result in alpha-cypermethrin residues above the recommended tolerances (0414740, E. 

Holman, October 2014 ). The FHE use of zeta-cypermethrin was previously included in the 

dietary exposure assessment, with the assumption of 100% crop treated for all commodities 

without an existing tolerance to account for this FHE use (D403600, E. Holman, 7 September 

2012). It is also not anticipated that the zeta-cypermethrin and alpha-cypermethrin FHE products 

would be used at the same time in a single FHE. Therefore, the addition of these FHE uses for 

alpha-cypermethrin will have no impact on the dietary risk estimates, as they are already covered 

in the existing assessment. The results of this dietary exposure assessment are summarized 

below. 

Dietary exposure to alpha-cypermethrin may occur from consuming treated crops or their 

processed commodities. Partially refined (probabilistic) dietary exposure assessments were 

performed in order to determine the exposure and risk estimates resulting from the use of 

cypermethrin, alpha-cypermethrin, and zeta-cypermethrin on the crops listed under 40 CFR 

180.418. HED has used modeling to estimate dietary exposure to the cypermethrins. The 

modeling uses conservative assumptions regarding residues of alpha-cypermethrin and its 

breakdown products in drinking water. Since monitoring data was not available for all 

commodities, the modeling uses a combination of highly conservative assumptions (i.e. tolerance 

1 Examples oflocations include hollow spaces in floors, walls, ceilings; cracks and crevices around pipes, doors, 

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

Page 4 of8 
level residues) and monitoring data with percent crop treated information for residues of alphacypermethrin and its breakdown products in food, as well as an extensive database of food 

consumption patterns for the U.S. population and population subgroups. 

For all registered and proposed uses, the acute dietary exposure estimates are below RED's level 

of concern (<100% aPAD at the 99.9th percentile of exposure). Dietary exposure (food and 

drinking water) for the cypermethrins is 18% of the aPAD for the U.S. population and 87% of 

the aP AD for all infants and children 1-2 years, the most highly exposed population subgroups. 

Cypermethrin and zeta-cypermethrin residential uses are included in the pyrethroidlpyrethrin 

cumulative risk assessment (CRA). The proposed products containing alpha-cypermethrin have 

an insignificant impact on the cumulative risk assessment. No dietary, residential, or aggregate 

risk estimates of concern have been identified in the single chemical assessment. In the 

cumulative assessment, residential exposure was the greatest contributor to the total exposure. 

Although there are residential 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-cypermethrin that are used in residential settings for outdoor (e.g., lawns) and 

indoor (e.g., fogger) broadcast treatments. Therefore, the proposed use will have no impact on 

the residential component of the cumulative risk estimates. 

2.0 HED Recommendations 

HED has no objection to registration of alpha-cypermethrin for the proposed products and 

establishment of tolerances as summarized in Table 2.2.3. No risks of concern or data 

deficiencies were identified. For further details on the earlier risk assessment of alphacypermethrin, see Middleton, K., D376098, 8/1112012. This assessment summarizes the 

toxicological database in detail, as well as the results from the dietary exposure, occupational and 

residential exposure, and aggregate risk assessments associated with the existing use pattern. No 

new quantitative exposure assessments were conducted associated with these new products, as 

they were covered in all cases by the previously assessed existing use pattern. 

2.1 Data Deficiencies 

None. 

2.2 Tolerance Considerations 

2.2.1 Enforcement Analytical Method 

Adequate tolerance enforcement methods are available in PAM Volume II for determining 

residues of cypermethrin, zeta-cypermethrin and alpha-cypermethrin in plant (Method I) and 

livestock (Method II) commodities. Both methods are gas chromatographic methods with 

electron-capture detection (GC/ECD), and have undergone successful Agency petition method 

validations (PMVs). Method I has a limit of detection (LOD) of0.01 ppm, and Method II has 

LODs of0.005 ppm in milk, and 0.01 ppm in livestock tissues. These methods are not 

Page 5 of8 
stereospecific; thus no distinction is made between residues of cypermethrin (all 8 

stereoisomers), zeta-cypermethrin (enriched in 4 isomers) and alpha-cypermethrin (2 isomers). 

The January 1994 FDA PESTDATA database (PAM Volume I) indicates that residues of 

cypermethrin are completely recovered (>80%) using multi-residue method Sections 302 (Luke), 

303 (Mills, Onley and Gaither) and 304 (Mills fatty food). 

2.2.2 International Harmonization 

Currently established US tolerances for cypermethrin, zeta-cypermethrin, and alphacypermethrin are included in the same listing in the 40 CFR, but have separate sections and 

different crops listed; where there are tolerances for both actives set on the same crop, the levels 

are the same. Mexico adopts US tolerances, and/or Codex maximum residue limits (MRLs), for 

its export purposes. Canada has established MRLs for cypermethrin only. There are currently 

no Canadian MRLs established for residues of alpha-cypermethrin or zeta-cypermethrin. There 

are multiple Codex MRLs for alpha-cypermethrin, but all are in conjunction with MRLs for total 

cypermethrin isomers (no MRLs have been established solely for alphacypermethrin). However, although the definitions differ formally, they are effectively 

harmonized since the tolerance-enforcement methods are not stereospecific, and thus do not 

distinguish between residues of cypermethrin, zeta-cypermethrin and alpha-cypermethrin. For 

enforcement purposes, the same moiety is being regulated. The current petition proposes alphacypermethrin tolerances at the same levels as existing zeta-cypermethrin tolerances in the 

corresponding commodities. 

For the proposed tolerances associated with this new use petition, there are no equivalent FHE 

use tolerances established by either Canada or Codex. Therefore there are no international 

harmonization issues associated with this petition. 

2.2.3 Recommended Tolerances 

HED recommends that 40CFR §180.418 be revised by establishing tolerances for the 

commodities listed in Table 2.2.3. 

HED has determined that the residue of concern for tolerance enforcement and risk assessment 

for alpha-cypermethrin is the parent compound. The tolerance enforcement methods for plant 

and animal commodities do not distinguish between cypermethrin, zeta-cypermethrin, and alphacypermethrin, even though they have separate tolerance listings in 40CFR § 180.418. 

TABLE2.2.3 Tolerance Summary for Alpba-cypermetbrin. 

Commodity Proposed Recommended Comments; Co"ect Commodity 

Tolerance (ppm) Tolerance (ppm) Definition 

Food commodities/feed 0.05 0.05 

commodities (other than those 

covered by a higher tolerance as a 

result of use on growing crops) in 

food/feed handling establishments 

Page 6 of8 
2.2.4 Revisions to Petitioned-For Tolerances 

No revisions to the tolerance levels in the petition, as proposed by BASF, were necessary. 

2.3 Label Recommendations 

None. 

3.0 Chemical Identity 

TABL:t!!3.0 Test Coinpc: und Nomen~•ature. "~ ~ ..;_ '"•,, •' " 

Compound chemical 

structure 

01 

(f< (R)-oloohol (IS)-oO-ooid 

\ N p~c c-o, ;c# p Cl \ CH II c.-' " ' o w" 0--o 

Cl H 0 \ t' \. N c)f:c-o, c-' 0 I CH3 -" C\ H H H/0--

CH3 rf 

(S)-alcohol (1R)-cis-acid 

Common name Alpha-cypermethrin 

Company experimental name BAS 310 I or AC 900049 

Empirical formula C22H19CbN03 

Molecular weight 416.3 glmol 

IUPAC name A racemic mixture comQrised of: 

(R)-a-cyano-3-phenoxybenzyl (1S,3S)-3-(2,2-dichlorovinyl)-2,2-

dimethylcyclopropanecarboxylate 

and 

(S)-a-cyano-3-phenoxybenzyl (1R,3R)-3-(2,2-dichlorovinyl)-2,2-

dimethylcyclopropanecarboxylate 

or (s:monymousl~} 

(R)-a-cyano-3-phenoxybenzyl (1S)-cis-3-(2,2-dichlorovinyl)-2,2-

dimethylcyclopropanecarboxylate 

and 

(S)-a-cyano-3 -phenoxybenzyl ( 1 R)-cis-3 -(2,2-dichlorovinyl)-2,2-

dimethylcyclopropanecarboxylate 

CAS name (R)-cyano(3-phenoxyphenyl)methyl (1S,3S)-re/-3-(2,2-dichloroethenyl)-2,2-

dimethylcyclopropanecarboxylate 

CAS registry number 67375-30-8 

End-use product (EP) BAS 310 40 I EC insecticide (EPA File Symbol 7969-EOI), 10.9% ai (w/w), 0.83 

lb ai/gal. 

3.1 Physical/Chemical Characteristics 

Alpha-cypermethrin has a very low water solubility, and relatively high octanol!water partition 

Page 7 of8 
coefficient (log Kow = 5.5). These values account for the low surface and groundwater 

concentrations determined by EFED's drinking water models. The chemical has low vapor 

pressure (2.55 X 10"9 mm Hg at 25°C), which decreases its potential to volatilize. 

3.2 Pesticide Use Pattern 

Two new products are proposed to controls a variety of pests (e.g., cockroaches, house 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 use pattern 

specified on the end-use product labels is summarized below in Table 3.2. 

Table 3.2. Summary of Directions for the Proposed End-Use Products for Alpha-cypermethrin. \ 

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

Equipment 

Indoor/Outdoor -Commercial, Residential and Food Handling Establishments 

Crack & Crevice (Void) TC-327 Residual time using application rates is up to 90 treatment using injection tube 0.0033 lb ai/can @I fWsec 

or tip. (EPA Reg. No. 499- days depending on pests. Reapply as necessary, 

Spot application using RTU LAO) but no more than 2 times per week. Applications 

container. Ready-to-use 0.0033 lb ail can@ 2 fWsec must be at least 3 days apart. Use with the 

Perimeter application using pressurized liquid 0.0033 lb ail can @ I 0 sec/site or supplied actuator, injection tubes/tip or other 

RTU container. (0.05%ai) hole 

BASF equipment. 

Crack & Crevice (Void) Residual time using application rates range from treatment using injection tube 0.0033 lb ailcan @I ft2/sec 

or tip. 30- 90 days depending on pests. Reapply as 

Spot application using necessary, but no more than 2 times per week. 

injection tube or low pressure TC-305 0.0033 lb ail can@ 2 fWsec Applications must be at least 3 days apart. Apply 

handheld equipment. EPA Reg. No. 499- with equipment designed for void applications. 

LTN) Product is to be used as a residual/supplemental 

Microencapsulated treatment. Use higher application rate to inhibit 

Perimeter, spot (spray) or liquid concentrate wood-infesting insect sand termite infestations in 

(3.0% ai) exposed tubing, cracks or cold joints (this is not a general surface application (0.25 lb ai/gal) 0.0039-0.0059 lb ail gal substitute for other termite treatments). using low pressure handheld (20-30 fl oz/1 0 gal) General surface applications for FHE may be used equipment. when the facility is not in operation and food/feed 

has been covered or removed from the application 

area. 

Lawns/Ornamentals 

TC-305 Not for use in commercial greenhouses or Perimeter (spray) application Microencapsulated 

using backpack sprayer or liquid concentrate 

0.00012 lb ailgal (ornamentals) nurseries. To be used in golf courses, hobby 

handheld equipment. (3.0% ai) 0.01 lb ail A (turf) greenhouse, interiorscapes, landscapes and lawns. 

(0.25 lb ailgal) Residual Time = 30-90 days depending on pest. 

Livestock Housing 

TC-305 0.0085 1b ai/A To be use in and on outside surfaces of outer Perimeter (spray) application Microencapsulated (1.0 fl oz/1,000 ft2) building. Treat a band of 6-10 ft around/adjacent using backpack sprayer or liquid concentrate 0.44lb ail A (5.0 fl oz/1,000 ft2 to the building. Use higher application rate to handheld equipment. (3.0%ai) 

(0.25 lb ailgal) for darkling beetles only) control darkling beetles only. 

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