1 

Docket Number EPA-HQ-OPP-2011-0885 

www.regulations.gov

Pyrethrins 

Summary Document 

Registration Review: Initial Docket 

December 2011 

3 

TABLE OF CONTENTS 

 

I. Preliminary Work Plan (PWP) 4 

II. Fact Sheet 14 

III. Summary of Data Gaps 23 

 

This Preliminary Work Plan and Fact Sheet summarize the Environmental Protection Agency’s 

current position based on the following documents: 

1. EFED Registration Review Preliminary Problem Formulation for Pyrethrins. November 

30, 2011. 

2. Pyrethrins. Human Health Risk Scoping Document in Support of Registration Review. December 

1, 2011. 

3. Pyrethrins: Review of Human Incidents. August 11, 2011. 

4. BEAD Chemical Profile for Registration Review: Pyrethrins (PC Code 069001). 

September 22, 2011. 

5. Pyrethrin (069001) Screening Level Usage Analysis (SLUA). January 21, 2011. 

6. Appendix A: Uses of Pyrethrins Eligible for Reregistration.

1 March 22, 2010. 

Supporting documents for the registration review of pyrethrins are located in docket EPA-HQOPP-2011-0885 at www.regulations.gov. 

 

1

 Appendix A is based on uses eligible after reregistration in 2006. 
4 

I. PRELIMINARY WORK PLAN 

Introduction

The Food Quality Protection Act (FQPA) of 1996 mandated a registration review program. All 

pesticides distributed or sold in the United States (U.S.) generally must be registered by the 

Environmental Protection Agency (EPA or the Agency), based on scientific data showing that 

they will not cause unreasonable risks to human health or the environment when used as directed 

on product labeling. The registration review program is intended to make sure that, as the ability 

to assess risk evolves and as policies and practices change, all registered pesticides continue to 

meet the statutory standard of no unreasonable adverse effects to human health or the 

environment. Changes in science, public policy, and pesticide use practices will occur over time. 

Through the registration review program, the Agency periodically reevaluates pesticides to make 

sure that as change occur, products in the marketplace can be used safely. Information on this 

program is provided at: http://www.epa.gov/oppsrrd1/registration_review/. 

The Agency is implementing the registration review program pursuant to Section 3(g) of the 

Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), and will review each registered 

pesticide every 15 years to determine whether it continues to meet the FIFRA standard for 

registration. The Agency will consider benefits information and data as required by FIFRA. The 

public phase of registration review begins when the initial docket is opened for each case. The 

docket is the Agency’s opportunity to state what it knows about the pesticide and what additional 

risk analyses and data or information it believes are needed to make a registration review 

decision. After reviewing and responding to comments and data received in the docket during 

this initial comment period, the Agency will develop and commit to a final work plan and 

schedule for the registration review of pyrethrins. 

Products containing the active ingredient pyrethrins are registered for use against a wide range of 

insects in many agricultural crop systems, such as lepidopterous caterpillars, leafhoppers, aphids, 

beetles, and thrips. They are also registered for use against a variety of urban insect pests, such 

as cockroaches and ants. Pyrethrins are registered for use on most fruit, nut, and vegetable crops, 

which includes crops such as corn, soybean, and wheat. Some of the non-agricultural uses 

include wood products (e.g., beams, decks, and pilings), residential areas, woodland areas, wood 

surfaces, residential and commercial buildings, food handling establishments, and mosquito 

abatement. 

The term “pyrethrins” refers to all six isomers (pyrethrin I, pyrethrin II, cinerin I, cinerin II, 

jasmolin I, and jasmolin II) found in pyrethrum extracts which are obtained from the dried and 

ground flowers of the pyrethrum plant, Chrysanthemum cinerariaefolium. Pyrethrins are most toxic 

to the target pest on contact, and have a quick “knockdown” effect. The majority of 

manufacturers formulate pyrethrins with a synergist compound to increase their toxic effect on 

target insects, such as with the pesticides piperonyl butoxide (PBO) or MGK-264, as well as with 

pyrethroids. Products formulated with pyrethrins alone are registered for use in organic 
5 

agriculture production. Pyrethrins were first registered as an insecticide in the 1950s. The 

Reregistration Eligibility Decision for Pyrethrins was competed in 2006. 

Anticipated Risk Assessment and Data Needs

The Agency anticipates requiring data for use in updating and refining the ecological risk 

assessment (including an endangered species risk assessment) and the human health risk 

assessment for all uses of pyrethrins. Below is a summary of the issues relevant to the 

registration review of pyrethrins and the data the Agency anticipates requiring. 

Ecological Risk: 

• The most recent ecological risk assessment for pyrethrins is reflected in the “Revised 

Pyrethrins RED Chapter After Additional 60-Day Comment Period, Phase 5” dated April 

4, 2007. 

• The Agency has not conducted a risk assessment that supports a complete endangered 

species determination for pyrethrins. The ecological risk assessment planned during 

registration review will allow the Agency to determine whether pyrethrins’ use has “no 

effect” or “may affect” federally listed threatened or endangered species (listed species) 

or their designated critical habitats. When an assessment concludes that a pesticide’s use 

“may affect” a listed species or its designated critical habitat, the Agency will consult 

with the U.S. Fish and Wildlife Service (USFWS) and/or National Marine Fisheries 

Service (NMFS) (the Services), as appropriate. 

• On January 19, 2011, the Center for Biological Diversity and the Pesticide Action 

Network North America filed a lawsuit in the United States District Court for the 

Northern District of California, against the Environmental Protection Agency (EPA) for 

allegedly failing to undergo consultation with the United States Fish and Wildlife Service 

and the National Marine Fisheries Service regarding the effects of over 350 pesticides, 

including pyrethrins, on over 200 endangered and threatened species throughout the 

United States (Center for Biological Diversity, et al. v. EPA, et al., No. C 11-00293 

(N.D.Cal.). 

• Data gaps exist in the environmental fate and ecological toxicity database for pyrethrins. 

The Agency anticipates needing the following data, in addition to the data already 

required in GDCI-069001-27992, for use in conducting a complete ecological risk 

assessment, including an endangered species assessment, for pyrethrins:
6 

Environmental Fate Data Gaps

o GLN 835.4100 Aerobic Soil Metabolism2

o GLN 835.4200 Anaerobic Soil Metabolism3

o GLN 835.4300 Aerobic Aquatic Metabolism4

o GLN 835.4400 Anaerobic Aquatic Metabolism5

o GLN 835.6100 Analytical method and associated independent laboratory 

validations in soil 

o GLN 835.6200 Analytical method and associated independent laboratory 

validations in water and sediment 

Ecological Toxicity Data Gaps

o GLN 850.1020 Acute Freshwater Invertebrate Toxicity (Hyalella azteca) – water 

column 

o GLN 850.2100 Avian Acute Oral Toxicity, Passerine 

o GLN 850.2300 Avian Reproduction Test, Quail/Duck6

o GLN 850.4100 Seedling Emergence, Tier II 

o GLN 850.4250 Vegetative Vigor, Tier II 

• Please refer to the EFED Registration Review Preliminary Problem Formulation for 

Pyrethrins dated November 30, 2011, located in docket EPA-HQ-OPP-2011-0885 at 

www.regulations.gov, for a more detailed discussion of the anticipated ecological risk 

assessment and data needs for pyrethrins.

Human Health Risk: 

• The most recent comprehensive human health risk assessment was conducted in support 

of the 2006 Reregistration Eligibility Decision (RED) and is dated March 16, 2006. 

Since the RED, additional human health assessments for pyrethrins occurred regarding a 

revision of the assessment for directly treating pets (01/24/08) and its use to treat in-home 

bedbug infestations (3/28/11). 

• The Food Quality Protection Act (FQPA) requires the Agency to consider the cumulative 

risks of chemicals sharing a common mechanism of toxicity. Pyrethrins are a member of 

the pyrethroid/pyrethrins common mechanism group (http://www.regulations.gov; EPAHQ-OPP-2008-0489-0006). The members of this group share the ability to interact with 

 

2

 Conduct studies in three different soil types; for metabolism studies, domestic soils are preferred. 3

 Conduct studies in four different soils; for metabolism studies, domestic soils are preferred. 4

 Conduct studies in two different sediment systems, one of which is of marine origin. 

5

 Conduct studies with two water/sediment systems, with one of the sediment systems from estuarine/marine origin. 6

 Tests are recommended for the technical product with waterfowl and an upland game bird species. 
7 

voltage-gated sodium channels ultimately leading to neurotoxicity. The cumulative risk 

assessment for the pyrethroids/pyrethrins was published on Nov. 9, 2011 and is available 

at http://www.regulations.gov; EPA-HQ-OPP-2011-0746. No cumulative risks of 

concern were identified, allowing the Agency to consider new uses for pyrethroid actives. 

For information regarding EPA’s efforts to evaluate the risk of exposure to pyrethroids, 

refer to http://www.epa.gov/oppsrrd1/reevaluation/pyrethroids-pyrethrins.html. 

• During registration review, the endpoints, doses, and safety factors used in the most 

recent human health risk assessments may be revisited based on current policy as well as 

to incorporate any new data received and determined to be adequate. The re-evaluation 

of the FQPA safety factor may be conducted following a final determination of the 

potential for increased susceptibility of infants and children to pyrethroid pesticides based 

on the review of all available data. 

• The uncertainty factor for Pyrethrins is currently 300X for acute dietary and short-term 

incidental oral (3X FQPA safety factor (SF) due to lack of a DNT and concerns for 

neurotoxicity, 10X for inter-species variation, 10X for intra-species variation). An 

uncertainty factor of 100X was applied to endpoints selected for oral exposure (10X for 

interspecies extrapolation, 10X for intraspecies variation). An uncertainty factor of 1000 

was applied to intermediate- and long-term inhalation endpoints due to both the lack of a 

DNT and the lack of a NOAEL for the identified endpoint, respiratory tract lesions. 

• Under FQPA, the Agency is required to apply a 10X SF to be protective of infants and 

children unless there is data to support a reduction or removal. The Agency’s current 

position is that there is sufficient evidence to reduce the FQPA SF to 1X for adults and 

3X for children <6 years of age. The 3X is based on age-dependent-pharmacokinetics 

and is further supported by physiologically-based pharmacokinetic (PK) model 

predictions of a 3-fold increase of pyrethroid concentration in juvenile target tissue 

compared to adults. A more complete description of the Agency’s reasoning behind a 3X 

FQPA SF for children can be found at www.regulations.gov; EPA-HQ-OPP-2011-0746-

0011. These UFs are subject to review and possible revision during the registration 

review. 

• The Agency anticipates conducting updated dietary (food and water), aggregate, 

residential, and occupational exposure risk assessments to include any changes in 

toxicological endpoints, doses, and procedures for risk assessment. 

• The residential and occupational exposure assessments may need to be updated to reflect 

current standard operating procedures and to incorporate new unit exposures, new 

transfer coefficients, and any new chemical-specific data submitted by the registrants, as 

well as reflecting current endpoints and points of departure. 
8 

• The Agency also anticipates conducting an updated drinking water exposure risk 

assessment during registration review. 

• The tolerance expression for pyrethrins in 40 CFR §180.128 and §180.905(a)(6) will be 

reviewed during registration review to ensure that it appropriately covers the metabolites 

and degradates of pyrethrins and that it specifies the residues to be measured in each 

commodity. 

• The Agency will modify tolerance levels as needed, and work to harmonize 

tolerances/maximum residue limits (MRLs), where possible, in key export markets 

during registration review. 

• A Generic Data Call-in (GDCI-069001-27992) was issued for pyrethrins in 2009 

following the RED. Most of the data requirement studies remain outstanding. This is 

discussed further in the Fact Sheet section of this document. 

• The Agency anticipates requiring the following toxicity data for use in conducting a 

complete human health risk assessment for pyrethrins: 

o GLN 870.7800 – Immunotoxicity 

• Pyrethrins are among several agricultural chemicals included in the Agricultural Health Study 

(AHS). The AHS began in 1993 and is a collaboration of the National Institute of Environmental 

Health Sciences (NIEHS), the National Cancer Institute (NCI), the EPA, and the National Institute 

for Occupational Safety and Health (NIOSH). Designed as a large long-term epidemiological 

study, the AHS collects and analyzes data on the health and work practices of nearly 90,000 

farmers and their families in Iowa and North Carolina who enrolled in the study before any disease 

developed. The study focuses particularly on farmers' exposure to 50 chemicals including many of 

the most widely used pesticides. As data are collected over a period of years, scientists can 

compare overall health outcomes for people who differ in whether they have had exposure to 

various chemicals. While these comparisons cannot conclusively demonstrate how exposure 

affects health, they can show some statistical associations. More information on the AHS can be 

found at: http://aghealth.nci.nih.gov. EPA is monitoring the results of the AHS and will consider 

this study in the registration review of Pyrethrins as appropriate. 

• Please refer to Pyrethrins. Human Health Risk Scoping Document in Support of Registration 

Review dated December 1, 2011, available in docket EPA-HQ-OPP-2011-0885 at 

www.regulations.gov, for a detailed discussion of the anticipated human health risk assessment 

and data needs. 
9 

Endocrine Disruptor Screening Program

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse 

outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and 

chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, 

reproductive, and general or systemic toxicity. These studies include endpoints which may be 

susceptible to endocrine influence, including effects on endocrine target organ histopathology, 

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, 

and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and 

chronic studies that assess growth, developmental and reproductive effects in different 

taxonomic groups. As part of its most recent reregistration decision for pyrethrins, EPA 

reviewed these data and selected the most sensitive endpoints for relevant risk assessment 

scenarios from the existing hazard database. However, as required by FFDCA section 408(p), 

pyrethrins are subject to the endocrine screening part of the Endocrine Disruptor Screening 

Program (EDSP). 

EPA has developed the EDSP to determine whether certain substances (including pesticide 

active and other ingredients) may have an effect in humans or wildlife similar to an effect 

produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator 

may designate.” The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine-related effects caused by the substance, and 

establish a dose-response relationship between the dose and the E, A, or T effect. 

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between 

October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 

chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. Pyrethrins are 

not among the group of 58 pesticide active ingredients on the initial list to be screened under the 

EDSP. Accordingly, as part of registration review, EPA will issue future EDSP orders/data callins, requiring the submission of EDSP screening assays for pyrethrins. For further information 

on the status of the EDSP, the policies and procedures, the list of 67 chemicals, future lists, the 

test guidelines and the Tier 1 screening battery, please visit our website: 

http://www.epa.gov/endo/. 

Timeline

 

The projected timeline for the completion of the pyrethrins registration review is presented 

below in Table 1. 
10 

Table 1. Projected Pyrethrins Registration Review Timeline7

Activity Estimated Date 

Opening the Docket 

Open Docket and Open Public Comment Period 2011 – December 

Close Public Comment Period 2012 – February 

Case Development 

Develop Final Work Plan (FWP) 2012 – May 

Issue Data Call-In (DCI) 2013 – Jan. - March 

Data Submission 2015 – Jan. - March 

Open Public Comment Period for Draft Risk Assessments 2016 – July – Sept. 

Close Public Comment Period 2016 – Oct. – Dec. 

Registration Review Decision 

Open Public Comment Period for Proposed Registration Review Decision 2017 – Jan. - March 

Close Public Comment Period 2017 – April - June 

Issue Registration Review Decision and Begin Post-Decision Follow-up 2017 

Total (years) 6 

Guidance for Commenters

The public is invited to comment on EPA’s preliminary work plan and rationale. The Agency 

will carefully consider all comments, as well as any additional information or data provided in a 

timely manner, prior to issuing a final work plan for the pyrethrins case. 

Trade Irritants 

Through the registration review process, the Agency intends to solicit information on trade 

irritants and, to the extent feasible, take steps toward facilitating irritant resolution. Growers and 

other stakeholders are asked to comment on any trade irritant issues resulting from lack of 

Maximum Residue Limits (MRLs) or disparities between U.S. tolerances and MRLs in key 

export markets, providing as much specificity as possible regarding the nature of the concern. 

Environmental Justice 

EPA seeks to achieve environmental justice, the fair treatment and meaningful involvement of all 

people, regardless of race, color, national origin, or income, in the development, implementation, 

and enforcement of environmental laws, regulations, and policies. To help address potential 

environmental justice issues, the Agency seeks information on any groups or segments of the 

population who, as a result of their location, cultural practices, or other factors, may have 

atypical, unusually high exposure to pyrethrins compared to the general population. Please 

 

7

 Any changes in the cumulative risk from the pyrethroid class of insecticides may impact this time estimate. 
11 

comment if you are aware of any sub-populations that may have atypical, unusually high 

exposure, compared to the general population. 

Water Quality 

On October 11, 2011, EPA issued its final decision regarding the waters EPA added to 

California's 2008-2010 list of impaired water bodies that require total maximum daily loads 

(TMDLs) pursuant to Clean Water Act, section 303(d), and 40 CFR 130.7(d)(2). This list 

includes 11 water body impairments due to pyrethroid chemicals (including pyrethrins), and 3 

water body impairments which list the pyrethroids bifenthrin, lambda cyhalothrin, 

esfenvalerate/fenvalerate, and permethrin as pollutants. More information on California’s 

additional impaired water body listings can be found at: 

http://www.epa.gov/region9/water/tmdl/california.html

On October 28, 2011, the California Department of Pesticide Regulation (DPR) announced 

proposed restrictions to 17 pyrethroid pesticides used by pest control applicators and 

maintenance gardeners in urban areas to protect water quality in urban areas. Restrictions would 

include reduced application rates around structures; and to prohibit applications during rain, 

when puddles are present, and over drains or natural drainage areas. More information about the 

proposed regulations are available on DPR’s website at: 

http://www.cdpr.ca.gov/docs/legbills/rulepkgs/11-004/11-004.htm. 

On October 31, 2011, EPA issued a final NPDES Pesticide General Permit (PGP) for point 

source discharges from the application of pesticides to waters of the United States. This action 

was in response to a 2009 decision by the U.S. Sixth Circuit Court of Appeals (National Cotton 

Council, et al. v. EPA) in which the court vacated EPA's 2006 Final Rule on Aquatic Pesticides 

and found that point source discharges of biological pesticides, and chemical pesticides that 

leave a residue, into waters of the U.S. were pollutants under the Clean Water Act (CWA). The 

Agency’s final permit covers operators that apply pesticides that result in discharges from the 

following use patterns: (1) mosquito and other flying insect pest control; (2) aquatic weed and 

algae control; (3) aquatic organism pest control; and (4) forest canopy pest control. 

The final pesticide general permit requires permittees to minimize pesticide discharges through 

the use of pest management measures, and monitor for and report any adverse incidents. While 

the permit’s requirements must be met as of October 31st, 2011, operators are not required to 

submit Notices of Intent (NOIs) until January 12, 2012. No permit will be required for 

discharges from agricultural runoff or irrigation return flows, both of which are exempt from 

permitting under the CWA. EPA’s pesticide general permit will cover pesticide applications in 

the areas where EPA is the permitting authority, which include Massachusetts, New Hampshire, 

New Mexico, Idaho, Oklahoma, Alaska, Washington, D.C., most U.S. territories and Indian 

country lands, and many federal facilities. For more information, please visit: 

http://www.epa.gov/npdes/pesticides. 
12 

Other Information 

Stakeholders are also specifically asked to provide information and data that will assist the 

Agency in refining risk assessments, including any species-specific ecological effects 

determinations for pyrethrins. The Agency is interested in receiving the following information: 

1. Usage data such as pounds active ingredient (a.i.) applied, area treated, typical use rates, 

and typical number of applications on the following sites: industrial sites, livestock, milk, 

and meat 

2. Importance to users in organic farming (e.g., frequency of use per season, application 

rates and methods in specific organic crops) 

3. Usage data for the agricultural crops that are not covered in the usage section of this 

document 

4. Usage data (pounds a.i. applied and area treated) for indoor/outdoor consumer use, use in 

food handling establishments/food processing establishments, and use in and around 

commercial and institutional facilities 

5. Confirmation on the following label information 

a. sites of application 

b. formulations 

c. application methods and equipment 

d. maximum application rates 

e. frequency of application, application intervals, and maximum number of 

applications per season and per year 

f. geographic limitations on use 

6. Use or potential use distribution (e.g., acreage and geographical distribution of relevant 

uses/use sites) 

7. Use history 

8. Median and 90th percentile reported use rates (lbs active ingredient(a.i.)/acre, lbs a.i./1000 

sq. ft.) from usage data – national, state and county 

9. Application timing (date of first application and application intervals) by use – national, 

state, and county 

10. Sub-county use site location data 

11. Directly acquired county-level usage data (not derived from state level data) 

a. maximum reported use rate (lbs a.i./acre) from usage data – county 

b. median and 90th percentile number of applications – county 

c. total pounds per year – county 

d. the year the pesticide was last used in the county/sub-county area 

e. the years in which the pesticide was applied in the county/sub-county area 

12. Typical application interval (days) 

13. State or local use restrictions 
13 

14. Ecological incidents (non-target plant damage and avian, fish, reptilian, amphibian, 

mammalian mortalities, and bee or beneficial insect mortalities) not already reported to 

the Agency 

15. Monitoring data 

Next Steps

After the 60-day public comment period closes, the Agency will review and respond to any 

comments received in a timely manner and then issue a Final Work Plan for the registration 

review of pyrethrins.
14 

II. FACT SHEET 

Background Information

• Registration Review Case Number: 2580 

• Pesticide Chemical (PC) Code: 069001 

• Chemical Abstracts Service (CAS) Number: 8003-34-7 

• Pyrethrins were first registered in the U.S. in the 1950s. 

• The Reregistration Eligibility Decision for pyrethrins was completed in June 2006. The 

RED and its supporting risk assessments are available in docket EPA-HQ-OPP-2005-

0043 at www.regulations.gov. 

• Technical registrants: Botanical Resources Australia Pty Ltd., Horizon Sopyrwa, 

McLaughlin Gormley King Co., Prentiss Inc., Pyranha Inc., Pyrethrum Board of Kenya, 

Pyrethrum Company of Tanzania Ltd., S.C. Johnson & Son Inc., Valent Biosciences 

Corp., Whitmire Micro-Gen Research Laboratories Inc. 

• Active registrations as of October 2011: 

o 601 Section 3 registrations 

o 1 Section 24(c) registration (Special Local Need) for use on lake margins in 

California 

• U.S. tolerances for pyrethrins range from 0.05 ppm to 3.0 ppm [40 CFR §180.128]. 

There is currently an exemption from a tolerance for raw agricultural commodities [40 

CFR §180.905(a)(6)]. 

• Pesticide Re-evaluation Division (PRD) Contact: Joel Wolf (wolf.joel @epa.gov) 

• Registration Division (RD) Contact: Richard Gebken (gebken.richard@epa.gov) 

Use and Usage Information

For additional details, please refer to BEAD Chemical Profile for Registration Review: 

Pyrethrins (069001), dated August 24, 2011; Pyrethrins (069001) Screening Level Usage 

Analysis (SLUA), dated January 21, 2011; and PRD Appendix A: Food/Feed & Non-Food/NonFeed Uses Considered in Registration Review Work Planning. Pyrethrins (069001), dated 

March 22, 2010; located in docket EPA-HQ-OPP-2011-0885 at www.regulations.gov. 
15 

• Pyrethrins are registered for hundreds of agricultural uses, including most fruit, nut, and 

vegetable crops, as well as most major acreage crops such as corn, soybean, and wheat. 

There are also indoor (greenhouse) uses listed for a variety of crops (e.g., tomatoes, 

ornamental plants, etc.). 

• Non-agricultural uses for pyrethrins include, but are not limited to, wood products (e.g., 

beams, decks, and pilings), woodland areas, wood surfaces, and zoos (enclosures and 

outdoor perimeter areas). Other non-agricultural use sites where pyrethrins are used 

include residential and commercial buildings, food handling establishments, institutional 

turf, nursery/greenhouse, and mosquito abatement areas. 

• Pyrethrins are formulated as granules, emulsifiable concentrates, ready-to-use solutions, 

and as pressurized gas and liquid. 

• Pyrethrins are commonly used in formulations with the pesticidal synergists PBO and 

MGK-264. These compounds enhance the insecticidal activity of pyrethrins. 

• Application methods in agricultural and non-agricultural uses are diverse and include: 

aerosol can, mist blower, metered release devices, total release aerosol, fixed wing 

aircraft, helicopter, truck-mounted ultra low volume (ULV) equipment, cold aerosol 

generator, hand held sprayers (high or low pressure handwands), thermal/cold/ULV 

fogging equipment, conventional dusting equipment (e.g., power duster, bulb duster, 

shaker can), outdoor misting systems, and irrigation systems. 

• The annual total agricultural usage averaged approximately 2,000 pounds active 

ingredient for the period 1998-2010, while the non-agricultural annual usage total for the 

period 2002-2008 is about 32,000 lbs. a.i. The largest markets in terms of total pounds of 

a.i. applied are lettuce (17%), winter wheat (16%), oranges (9%), and strawberries (8%). 

The highest total area treated (TAT) are winter wheat (20%), and soybeans and lettuce 

(9% each). 

Recent and Pending Actions

• Product mitigation identified in the 2006 RED is still being implemented, as such, not all 

pyrethins labels reflect the most up-to-date label language 

• On May 5, 2011, the Agency accepted a label language amendment for pyrethrins use on 

mattresses and box springs for bed bug infestations. This is not considered a “new use” 

because indoor residential uses are already registered for the product. 
16 

Ecological Risk Assessment Status

The following are key findings from the most recent ecological risk assessments regarding the 

environmental fate, ecological effects, and risks of pyrethrins. Please refer to the EFED 

Registration Review Preliminary Problem Formulation for Pyrethrins, November 30, 2011, 

located in docket EPA-HQ-OPP-2011-0885 at www.regulations.gov, for a detailed discussion. 

• The most recent ecological risk assessment for pyrethrins is contained in the “Revised 

Pyrethrins RED Chapter After Additional 60-Day Comment Period, Phase 5” dated April 

4, 2007. 

Ecological Effects: 

• Based upon toxicity data and other information, acute risks from the use of pyrethrins to 

mammals, birds, terrestrial amphibians, and reptiles is below the Agency’s level of 

concern (LOC). 

• The review indicated risk concerns for freshwater and estuarine/ marine organisms, 

including benthic organisms. Chronic risk estimates exceeded the LOC triggers for 

estuarine/ marine invertebrates, while fish (freshwater and estuarine/ marine) and 

freshwater invertebrates were found not to be at chronic risk from exposure to pyrethrins 

in the water column. 

• On an acute basis, pyrethrins are highly toxic to honey bees. 

• The Agency also evaluated the pharmacological uses of pyrethrin using the “Down-theDrain” module of the Exposure and Fate Assessment Screening Tool (E-FAST) model 

and found that aquatic LOCs were not exceeded for freshwater or estuarine/marine 

organisms. 

Human Health Risk Assessment Status

The following are key findings from the most recent human health risk assessments conducted 

for pyrethrins registered uses. Please refer to Pyrethrins. Human Health Risk Scoping 

Document in Support of Registration Review, December 1, 2011, located in docket 

EPA-HQ-OPP-2011-0885 at www.regulations.gov, for a detailed discussion of the human health 

risk assessment status. 

• The most recent human health risk assessment was conducted in support of the 2006 

Reregistration Eligibility Decision (RED) and is dated March 16, 2006. Since the RED, 

additional human health assessments for pyrethrins occurred regarding its use to treat in-
17 

home bedbug infestations (3/28/11) and a revision of the assessment for directly treating 

pets (1/24/08). 

Human Studies:

• Past pyrethrins risk assessments rely in part on data from studies in which adult human 

subjects were intentionally exposed to a pesticide to determine their dermal and 

inhalation exposure. Many such studies, involving exposure to many different pesticides, 

comprise generic pesticide exposure databases such as the Pesticide Handlers Exposure 

Database (PHED), the Agricultural Reentry Task Force (ARTF) Database, the 

Agricultural Handlers Exposure Task Force (AHETF), and the Outdoor Residential 

Exposure Task Force (ORETF) Database. 

• EPA has reviewed all the studies supporting these multi-pesticide generic exposure 

databases, and has found no clear and convincing evidence that the conduct of any of 

them was either fundamentally unethical or significantly deficient relative to the ethical 

standards prevailing at the time the research was conducted. All applicable requirements 

of EPA’s Rule for the Protection of Human Subjects of Research (40 CFR Part 26) have 

been satisfied, and there is no regulatory barrier to continued reliance on these studies. 

Hazard Characterization: 

• The major target organs for pyrethrins-induced toxicity are the nervous system, liver, and 

thyroid. Neurobehavioral effects were observed in rats and mice following acute, 

subchronic, and chronic exposure, and neuropathological lesions were observed in rats 

following acute exposure. Following inhalation exposure, neurobehavioral effects were 

observed initially, and histopathological lesions of the lungs/respiratory tract were 

observed at all dose levels. Pyrethrins show no significant developmental or reproductive 

effects in rats. 

• Pyrethrins were classified as “Suggestive Evidence of Carcinogenicity, but Not Sufficient 

to Assess Human Carcinogenic Potential” because there was suggestive evidence that 

pyrethrins are carcinogenic based on weight-of-the-evidence considerations. 

• Toxicity points of departure (PODs) were selected for oral and inhalation exposure 

pathways for the risk assessment conducted in the 2006 RED. No endpoints were 

selected for dermal exposure since no systemic effects were observed at the limit dose in 

the 21-day dermal toxicity study in rabbits. 

• Since there were adequate developmental toxicity studies in rats and rabbits, an adequate 

two-generation reproduction study in rats, and no residual uncertainties that indicate the 

need for retaining an additional factor, the FQPA factor was reduced to 1X. An 
18 

uncertainty factor of 100X was applied to endpoints selected for oral exposure (10X for 

interspecies extrapolation, 10X for intraspecies variation). An uncertainty factor of 300 

was applied to acute dietary and short-term incidental oral endpoints (conventional 

uncertainty factor of 100X plus an additional 3X for the lack of a DNT and concerns for 

neurotoxicity). An uncertainty factor of 1000 was applied to intermediate- and long-term 

inhalation endpoints due to both the lack of a DNT and the lack of a NOAEL for the 

identified endpoint, respiratory tract lesions. 

Summary of Risks: 

Dietary

• The dietary assessment (food and water) did not indicate risk estimates of concern.

Residential 

• Residential scenarios assessed include short-term and intermediate-term exposures for 

handlers (i.e., mixers, loaders, applicators) that occur during application of pyrethrins and 

short-term, post-application exposure from activities in treated areas. 

• In the assessments for the pyrethrins RED there was no residential risk estimates of 

concern identified when pyrethrins were mixed, loaded, applied, or handled by 

homeowners. There were several residential post-application scenarios where risk 

estimates of concern were identified: 1) indoor broadcast dust applications to carpets, 2) 

indoor metered release systems, and 3) outdoor residential misting systems. In order to 

mitigate these risks, the RED specified amended label language, including the prohibition 

of metered release devices in residential indoor areas. In addition, the Agency required 

data to confirm the assumptions used in its risk assessment. 

Aggregate

• The most recent risk assessment included aggregate assessments that considered exposure 

from food, drinking water, and residential uses. Acute aggregate exposures assessments 

for pyrethrins showed no risk estimates of concern. 

• The short-term aggregate exposure assessment for pyrethrins showed no risk estimates of 

concern for adults and children using the Aggregate Risk Index (ARI) method since the 

dietary contribution included high-end field trial data and assumed 100% percent crop 

treated for all but a few crops. 
19 

Occupational

• A number of occupational exposure scenarios were assessed for agricultural, forestry, 

professional pest control operator, and mosquito control applications of pyrethrins. The 

scenarios assessed that indicated potential risk concerns for occupational handlers were 

those using wettable powder formulations over the intermediate-term exposure duration. 

Mitigation measures, such as the use of water soluble packaging for all wettable powder 

formulations were specified in the RED. These mitigation measures addressed the 

identified risk concerns. 

Cumulative

• The Food Quality Protection Act (FQPA) requires the Agency to consider the cumulative 

risks of chemicals sharing a common mechanism of toxicity. Pyrethrins are a member of 

the pyrethroid/pyrethrins common mechanism group (http://www.regulations.gov; EPAHQ-OPP-2008-0489-0006). The members of this group share the ability to interact with 

voltage-gated sodium channels ultimately leading to neurotoxicity. The cumulative risk 

assessment for the pyrethroids/pyrethrins was published on Nov. 9, 2011 and is available 

at http://www.regulations.gov; EPA-HQ-OPP-2011-0746. No cumulative risks of 

concern were identified, allowing the Agency to consider new uses for pyrethroid actives. 

For information regarding EPA’s efforts to evaluate the risk of exposure to pyrethroids, 

refer to http://www.epa.gov/oppsrrd1/reevaluation/pyrethroids-pyrethrins.html. 

Incidents

Ecological Incidents: 

• The Agency reviewed the Ecological Incident Information System (EIIS), which is 

maintained by the EPA Office of Pesticide Programs (OPP), and the Avian Monitoring 

System (AIMS), which is maintained by the American Bird Conservancy, for ecological 

incident reports associated with the use of pyrethrins in the U.S. 

• The EIIS database contained 7 major incidents involving pyrethrins. The reports included 

2 fish incidents and 5 plant incidents. With respect to the likelihood that pyrethrins 

caused the reported incidents, the certainty ranged from possible to probable. Four of the 

incidents resulted from registered uses, two were misuses and one use pattern is 

unknown. The AIMS database contains no avian incidents involving pyrethrins. 

• For pyrethrins, the registrants have reported 231 minor plant incidents. All reported 

incidents occurred between 1995 and 2010 and involved currently registered products. 
20 

Human Health Incidents: 

• The Agency reviewed the OPP Incident Data System (IDS) for human health pesticide 

incident data associated with the active ingredient pyrethrins in the U.S. to identify 

potential patterns on the frequency and severity of health effects attributed to pyrethrins 

exposure. The IDS aggregate summaries from January 1, 2006 to June 6, 2011 include 

4,375 minor, unknown, or no effects outcomes reported for pyrethrins (664 of the 

exposures are classified as an unknown/no effects outcome, 3,711 of the exposures are 

classified as resulting in a minor outcome). For the Main IDS, from January 1, 2006 to 

June 6, 2011, there were 13 exposures reported for single chemical only in the database, 

and 803 additional exposures that involved more than one chemical. 

• In general, a relatively high frequency of incidents were reported involving pyrethrins. 

Although most of these incidents were of low severity, it appears exposures to pyrethrins 

have the potential to result in high severity outcomes. Consequently, based on the 

frequency of exposures and the potential for exposures to result in high severity 

outcomes, these incident data warrant further analysis in the preliminary risk assessment 

phase of Registration Review. 

• The Agency has considered/discussed the potential relationship between pyrethrum, 

pyrethrins and pyrethroids and allergic/asthmatic effects in a variety of analyses (e.g., 

EPA's OPP "Recognition and Management of Pesticide Poisonings" manual, the EPA 

Office of Radiation and Indoor Air commissioned a review by the National Academy of 

Sciences’ Institute of Medicine about the relationship between asthma and exposure to 

various substances, including pesticides; and OPP staff have conducted pyrethrins and 

various pyrethroid incident reviews). Most recently, a report by the Center for Public 

Integrity prompted EPA to conduct its latest review of pyrethrins and pyrethroid incidents 

to identify any trends in the data. Agency scientists have concluded that there does not 

appear to be a clear relationship between pyrethrins/pyrethroid exposure and 

asthma/allergies8

. However, the pyrethrins registrants committed to a product 

stewardship program that involves outreach to physicians and Poison Control Centers 

with better guidance and diagnostic standards, as well as prospective in-depth follow-up 

of reported cases in order to better understand the cause of the incidents with pyrethrins.9

Tolerances and International Harmonization

• U.S. tolerances for pyrethrins are located at 40 CFR §180.548 and §180.905(a)(6). 

 

8

 http://www.epa.gov/oppsrrd1/reevaluation/pyrethrins-pyrethroids-asthma-allergy-9-18-09.pdf 9

 This is a 5-year program requiring annual reports. To date, one annual report has been submitted. 
21 

• A table listing the differences between U.S. tolerances and Canadian, Mexican, and 

CODEX Maximum Residue Limits (MRLs) for pyrethrins is included in the Pyrethrins. 

Human Health Risk Scoping Document in Support of Registration Review  ̧ dated 

December 1, 2011, available in docket EPA-HQ-OPP-2011-0885 at 

www.regulations.gov. 

• Currently, there are no harmonization issues with Canada, CODEX, or Mexico. During 

registration review, if any Codex MRLs have been established, the Agency anticipates 

harmonizing the U.S. tolerances with the Codex MRLs when the data warrant 

harmonization. 

Data Call-Ins

• A DCI was issued to pyrethrins technical registrants in May 2009 to address data gaps 

identified in the 2006 RED. These data, along with the anticipated registration review 

data requirements that are required, submitted, and determined to be adequate will be 

used in conducting the forthcoming human health and ecological risk assessments for the 

registration review of pyrethrins. The following data for GDCI-069001-27992 have been 

required: 

Data that have been submitted 

o GLN 860.1850 Confined accumulation in rotational crops 

Data still outstanding 

o GLN 830.7050 UV/Visible absorption 

o GLN 850.1075 Freshwater and marine fish acute toxicity 

o GLN 850.1350 Mysid chronic toxicity 

o GLN 850.1400 Fish early-life stage toxicity test 

o GLN 850.1500 Fish full life cycle toxicity 

o GLN 850.4100 Terrestrial plant toxicity, Tier I (seedling emergence) 

o GLN 850.4150 Terrestrial plant toxicity, Tier I (vegetative vigor) 

o GLN 850.4400 Aquatic plant toxicity test using Lemna spp. Tiers 1 and II 

o GLN 850.5400 Algal toxicity, Tiers I and II 

o GLN 860.1380 Storage stability data 

o GLN 860.1500 Crop field trials (for various commodities)10

o GLN 860.1520 Processed food/feed (for various commodities) 

o GLN 870.6300 Developmental neurotoxicity study 

o GLN 875.1400 Inhalation exposure—indoor (metered release devices) 

o GLN 875.1400 Inhalation exposure - indoor - ULV fogger 

 

10 See Appendix D: Required Crop Field Trial Data in Pyrethrins. Human Health Risk Scoping Document in 

Support of Registration Review, December 1, 2011 for a complete list of the required crop field trials. 
22 

o GLN 875.1700 Product use information (outdoor residential misting 

systems) 

o GLN 875.2500 Inhalation exposure – residential misting systems 

o Non-GLN Chronic freshwater sediment toxicity (Chironomus spp. and 

Hyalella azteca)

11

o Non-GLN Chronic estuarine sediment toxicity12

o Non-GLN Pyrethrins stewardship program13

o Non-GLN Developmental thyroid assay 

Data compensation 

o GLN 840.1100 Spray droplet size spectrum 

o GLN 840.1200 Spray drift field deposition 

o GLN 875.1300 Inhalation exposure—outdoor (ORETF) 

o GLN 875.2300 Indoor surface residue dissipation 

o GLN 875.2400 Dermal exposure (loading and application of dust) 

o GLN 875.2500 Inhalation exposure – post application (fogging) 

o GLN 875.2500 Inhalation exposure - post application (trigger pump 

sprayer) 

o GLN 875.2500 Inhalation exposure – post application (loading and 

application of dust) 

Labels 

• Active Section 3 labels for pyrethrins can be obtained from the Pesticide Product Label 

System (PPLS) website: http://oaspub.epa.gov/pestlabl/ppls.home. 

 

11 In more recent DCIs this data requirement is indicated as Non-GLN/Test # 100.4 Whole Sediment: chronic 

invertebrates freshwater and marine (Hyalella azteca) and Non-GLN/Test # 100.5 Whole Sediment: chronic 

invertebrates freshwater and marine (Chironomus dilutes). 

12 In more recent DCIs this data requirement is indicated as Non-GLN Whole Sediment: chronic invertebrates 

freshwater and marine (Leptocheirus plumulosus). 

13 This is a 5-year program requiring annual reports. To date, one annual report has been submitted. 
23 

III. SUMMARY OF DATA GAPS 

A summary of the anticipated data needs for pyrethrins registration review is presented in Table 

2. 

Table 2. Summary of Anticipated Data Needs for Pyrethrins

Guideline Number Anticipated Data Requirement Test 

Material 

 Estimated 

Timeframe 

 (Measured 

in Months 

from DCI 

Receipt) 

835.4100 Aerobic Soil Metabolism TGAI 24 

835.4200 Anaerobic Soil Metabolism TGAI 24 

835.4300 Aerobic Aquatic Metabolism TGAI 24 

835.4400 Anaerobic Aquatic Metabolism TGAI 24 

835.6100 Analytical method and associated independent laboratory 

validations in soil 

TGAI 24 

835.6200 Analytical method and associated independent laboratory 

validations in water and sediment 

TGAI 24 

850.1020 Acute Freshwater Invertebrate Toxicity (Hyalella azteca) – 

water column 

TGAI 12 

850.2100 Acute Avian Oral, Passerine TGAI 12 

850.2300 Avian Reproduction Quail/Duck TGAI 24 

850.4100 Seedling Emergence, Tier II TGAI 12 

850.4250 Vegetative Vigor, Tier II TGAI 12 

870.7800 Immunotoxicity TGAI 12