UNITED STATES ENVIRONM ENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

JAN 23 2013 

OFFICE OF CHE\11CAI.. SAFEn' 

A~D POI..Ll TION PRE\'EYJ'ION 

.OEc;:ISION MEMORANDUM 

SUBJECT: 

:FROM: 

TO 

Registration ofNew Active Ingredient Alpha-Cypermethrin 

Lois Rossi, Director ~-0 \(~ Registration DivisiQl/ \ \W>\ \3 

Steven Bradbury, Ph.D., Director 

Office of Pesticide Programs 

This memorandum recommends that you concur on the registration and the establishment of 

w le ·ances for the new active ingredient alpha-cypermethrin for uses on alfalfa, brassica vegetables, citrus 

rruil5, corn (field, pop, seed, and sweet), cotton, cucurbits, fruiting vegetables, leafy vegetables, legume 

egc~tables, rice, root and tuber vegetables, soybeans, sugar beets, tree nuts, and wheat. A summary of the 

hurr.an health and ecological risks is included in the attached Registration Decision Document. The Science 

Div .sions have reviewed all available data and the Registration Division has concluded that the criteria for 

unccmditional registration under FIFRA Section 3(c) (5) have been met. 

;tu:c;:OMMENDATIONS 

I recommend that you concur with the establishment of tolerances and the unconditional 

egi tration ofthe new active ingredient alpha-cypermethrin under FIFRA Section 3(c) (5). 

Concur: ____ ~~~===E~~~~~~----~ 

S even Braabury, Ph.D., Director 

Office of Pesticide Programs 

Nonconcur: -------------------------------- Steven Bradbury, Ph.D., Director 

Attcchments:, Regis)Tation Decision Document 

Pesticide Tolerances, Final Rule 

Summary Document 

Office of Pesticide Programs 

2

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, brassica 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-cypermethrin 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 alphacypermethrin 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 against 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 

cypermethrins, is active against a wide range of insect pests important in agricultural 

production.

Alpha-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, cypermethrin 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. 

Registration of alpha-cypermethrin relies on alpha-cypermethrin data, as well as 

previously submitted data for the related registered insecticides, cypermethrin and zetacypermethrin. Cypermethrin, zeta-cypermethrin and alpha-cypermethrin are isomer mixtures 

of the same chemical. Cypermethrin consists of a mixture of eight isomers (four 

diastereoisomeric pairs). Zeta-cypermethrin is composed of four of the eight isomers of 

cypermethrin, and also contains one of the isomers in alpha-cypermethrin. Alphacypermethrin consists of two of the four cis-isomers of cypermethrin. Studies conducted to 

support the registrations of cypermethrin and zeta-cypermethrin are applicable to the 

registration of alpha-cypermethrin. Therefore, the following discussions regarding 

“cypermethrin” include cypermethrin, alpha-cypermethrin and zeta cypermethrin as a group 

of similarly 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 considered not only the exposure 

associated with the proposed food uses for 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 cypermethrins 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 selected toxicity 

endpoints and points of departure for risk assessment were based on the proposed use 

patterns for the cypermethrins, and the expected exposure profile for dietary, dermal, 

inhalation, and incidental oral exposures. 

The toxicity endpoints for cypermethrin, zeta-cypermethrin, and alpha-cypermethrin (as a 

group) are based on 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 

effect levels (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 is the 

robustness of the dose-response data. The guideline experimental toxicology studies 

available for the cypermethrins are generally high quality and were considered in the POD 

selection process and in the weight of the evidence evaluation. Observations 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 Wolansky et. al. (2006) study and the resulting 
4

well-defined dose-response curve, it was determined that the study provided the most robust 

data set for extrapolating risk from the cypermethrins. 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 peak 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 BMDL1SD

value of 7.16 mg/kg, based on decreased locomotor activity at the BMD1SD 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 associated 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 

BMDL1SD value of 7.16 mg/kg, based on decreased locomotor activity and the BMD1SD 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 study 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 to 

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 channel 
5

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 rat 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 the 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 shortand 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 the inhalation study are consistent with the pyrethroid profile and are 

protective of neurotoxicity. 

 For cypermethrin, human equivalent concentrations (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 respiratorytract 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 1.87 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 0.008mg/L. For the current risk 

assessment, the use of 24 hours of exposure to calculate an HEC is considered protective 

and very conservative since handler 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 did 
6

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. The 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 gain) 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 

retained 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.

 .

Cancer Classification and Risk Assessment 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 estimation 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 result 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 tumors 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 evidence 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 literature 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 risk 
7

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 safety 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 

interspecies 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 additional 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 alphacypermethrin; 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 short-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 registered 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 estimates and used these to 
8

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 using 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, these exposure do 

not exceed the agency’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 

exposures do not exceed the Agency’s level of concern.

E. Water Residue Profile and Drinking Water Risk

 In 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-cypermethrin (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 on 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 residues of alpha-cypermethrin in drinking water 

from the use of cypermethrins 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 currently 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, and 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 water 

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, alphacypermethrin, 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 treated 

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 estimates (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. 

The current assessment updates prior assessments 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 

updated anticipated residue levels and percent crop treated estimates where appropriate. No 

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 field 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 tolerance-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 treated (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 dosing 
10

duration, and therefore, the acute dietary endpoint is protective 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 exposure 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, with an inhalation LOC of 30 and a 

dietary LOC of 100. Therefore, 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 than 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).

Therefore 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 consider 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 sodium 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 cumulative risk assessment. However, the 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 levels; 
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 cumulative 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-OPP2011-0746). 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 

techniques 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 assessed. 

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 are 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 acreage.

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 postapplication activities in previously treated fields. Although a quantitative occupational 

post-application inhalation exposure assessment was not performed, an inhalation 
12

exposure assessment was performed for occupational/commercial handlers. 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 Dermal 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 shortand intermediate-term dermal post-application exposures are expected for workers reentering 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. The 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 irritation, 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 alphacypermethrin.

III. 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. Alphacypermethrin is considered immobile in soils based on the FAO soil mobility 

classification (Koc as high as 144,662 L/Kg) and its potential to leach into groundwater is 

low (USEPA, 2006a). 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 moderate 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 persist 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 (Koc) for cypermethrins ranged from approximately 21,000 

to 328,500 L/Kg in four soils (sand, sandy loam, silty loam and clay). If released into 

water, cypermethrins 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-m3/mol), indicates that volatilization from water and 

soil will not be an important transport process. 
13

Bioconcentration: 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, alpha-cypermethrin is being metabolized extensively in the fish, 

which suggests a reduced potential for alpha-cypermethrin to biomagnify in terrestrial 

organisms. 

Degradation: The major degradation products of the base catalyzed hydrolysis of 

cypermethrin 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 waters, 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 days 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; 

however, 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 degradation products.

Aquatic exposure: Based upon the environmental fate properties of alphacypermethrin 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 exposure and ecotoxicity 

data to evaluate the likelihood of adverse ecological effects. The means of integrating the 
14

results of exposure and ecotoxicity data is called the quotient method. For this method, 

risk quotients (RQs) are calculated by dividing exposure 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 indicate 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 registered enriched isomeric mixture, zetacypermethrin. 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 described in Appendix A of the risk 

assessment.

A screening-level risk assessment of the proposed uses suggests that alphacypermethrin 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 alphacypermethrin suggest that the persistence of the alpha enriched mixture is less persistent 

than that of zeta-cypermethrin and racemic 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.

IV. 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 

Technical), 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 

notice 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 document for alpha-cypermethrin and supporting documents into docket number 

EPA-HQ-OPP-2012-0185 for a 30-day public comment period. No comments were 

received.
15

A. Labeling Requirements

In order to mitigate risks to non-target plants and animals, EPA requires 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 advisories 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 concerns 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 restrict 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 prohibits 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 replaces existing cypermethrin or zetacypermethrin usages, and 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 usage 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 unconditional 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 vegetables, sorghum, soybeans, sugar beets, tree nuts, and 

wheat, 2) the uses of alpha-cypermethrin will not cause unreasonable adverse effects on 

the environment, and 3) that the registration of alpha-cypermethrin will provide a net risk 

reduction with regard to overall use of the entire suite of registered cypermethrin 

products, as alpha-cypermethrin will 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 of the already registered 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 grants this unconditional registration.