1 

Docket Number EPA-HQ-OPP-2011-0885 

www.regulations.gov

Pyrethrins 

Final Work Plan 

Registration Review 

May 2012 
Pyrethrins

Final Work Plan

Registration Review

Case # 2580

Approved By:

~-?~~4J

Richard P. Keigwin, Jr.

Director

Pesticide Re-evaluation Division

5J \8' 1..:1.0 1;:L

Date

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Introduction

This is the Environmental Protection Agency’s (EPA’s) Final Work Plan for the registration 

review of pyrethrins. This work plan includes the expected registration review timeline. The 

work plan also addresses public comments received concerning the Preliminary Work Plan in 

the Summary Document, which was posted in the pyrethrins registration review docket (EPAHQ-OPP-2011-0885), and any other comments concerning the initial docket postings. The 

Summary Document provided information on what EPA knows about the pesticide and what 

additional risk analyses and data or information the Agency believes are needed to make a 

registration review decision. 

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

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. The public phase of registration review begins when the initial docket is 

opened for each case. Information on this program is provided at: 

http://www.epa.gov/oppsrrd1/registration_review/. 

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 compounds (pyrethrin 1, pyrethrin 2, cinerin 1, cinerin 2, 

jasmolin 1, and jasmolin 2) 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 

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

Reregistration Eligibility Decision for Pyrethrins was competed in 2006. 
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Comments Received on Preliminary Work Plan

McLaughlin Gormley King Co. (MGK), registrant of technical grade pyrethrins, and Physicians 

Committee for Responsible Medicine (PCRM) provided the only two submissions to the docket 

during the 60-day public comment period on the planned human health and environmental fate 

and ecological risk assessments discussed in the pyrethrins Preliminary Work Plan (PWP). The 

comments do not alter the Agency’s PWP for the registration review of pyrethrins. While the 

data gaps identified in the PWP remain unchanged, because guideline number 850.1020 is still in 

draft, the study is now listed as guideline number 850.1010. This change does not alter the data 

being required. For further discussion on these comments, please see the Summary of 

Comments and Agency Responses section of this document as well as the supporting response to 

comment documents included in the docket, EPA-HQ-OPP-2011-0885. 

Summary of Comments and Agency Responses

Comments related to the Environmental Fate and Ecological Problem Formulation 

MGK Comment: With respect to pyrethrins in the environment, they are one of the shortestlived active ingredients, with half lives on the order of hours rather than days. Further, with 

respect to the CBD1 lawsuit, we believe that ecological risk assessments on pyrethrins will not 

trigger levels of concern in the environment. 

EPA Response: EPA acknowledges pyrethrins appear to be labile to certain routes of 

degradation/ metabolism. Under anaerobic conditions, it seems to persist longer (t1/2 = 86 

days). In the last risk assessment performed on the pyrethrins, there were exceedances of 

acute and chronic levels of concern for both freshwater and estuarine/marine aquatic 

animals, as well as benthic organisms. The acute and chronic levels of concern (LOCs) 

were not exceeded for listed or non-listed mammals or birds. For environmental fate and 

ecological risk assessment supporting the forthcoming registration review, all the 

available environmental fate and ecological effects data will be evaluated. 

MGK Comment: Ecological Toxicity Data Gaps, the Pyrethrins Joint Venture and Piperonyl 

Butoxide Task Force II, of which MGK is a member, has provided EPA with a special study 

design under the GLN 850.1020, to investigate the acute aquatic toxicity of combinations of 

concentrations of pyrethrins and piperonyl butoxide (PBO). Studies are underway determining 

the LD50 of Hyalella azteca to these different combinations of concentrations. We will be able to 

determine both the critical concentrations of PBO and pyrethrins as well as what ratio of PBO to 

pyrethrins result in the greatest LD50. This will be extremely useful information from which data 

with other pyrethroids can inform any synergistic effect of PBO and pyrethroids in the 

environment. 

EPA Response: EPA acknowledges the comment and supports the data submission. 

 

1

 CBD refers to Center for Biological Diversity. 
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MGK Comment: With respect to Water Quality, pyrethrins have a very short half life in the 

environment, degrading rapidly in sunlight. Therefore we are very surprised to read of 11 bodyof-water impairments listing pyrethrins. We will respond further during Registration Review. 

EPA Response: It was noted that the summary document says that there are several 

bodies of water impaired due to the presence of pyrethroids (not pyrethrins). However, 

pyrethroids are related synthetic chemicals with a similar structure. EPA will be 

investigating whether pyrethrins were directly or indirectly implicated in these 

impairments. 

MGK Comment: With respect to CDPRs recent proposed restrictions to 17 pyrethroids used by 

pest control applicators, we would like to point out to EPA that pyrethrins is NOT one of the 17. 

EPA Response: Acknowledged. The proposed DPR Regulation No. 11-004, which 

contains the full list of 17 pyrethroid active ingredients affected by the rule, is located at 

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

MGK Comment: By direct contact pyrethrins is highly acutely toxic to bees, but we would like 

to point out because of the short half-life in the environment pyrethrins would not have longterm toxicity to bees exposed to treated foliage over time. 

EPA Response: EPA will characterize the environmental fate of pyrethrins using 

appropriate models and field residue data. Regarding the potential for pyrethrins to cause 

adverse effects on bees as a result of exposure due to existing uses of the chemicals, EPA 

will utilize available information to qualitatively characterize potential risks to bees and 

the need for appropriate label language. EPA further notes that procedures for 

quantifying risks to honeybees and other insect pollinators and the data needed to inform 

that process will be evaluated at a FIFRA Scientific Advisory Panel (SAP) currently 

anticipated in fall, 2012. Based on the outcome of this SAP, the need for any additional 

data for evaluating risks to pollinators and/or appropriate label language will be 

determined. 

PCRM Comment: The Summary Document indicates that the Agency may request testing for 

avian acute oral toxicity, however, available data already exists for six pyrethroids (allethrin, 

cypermethrin, metofluthrin, resmethrin, tefluthrin, and tetramethrin), with the Agency requesting 

testing for an additional 10 through the Registration Review process. While it is understood that 

the common mechanism group designation applies to mammalian toxicity, the Agency should 

consider whether this is also the case for avian acute toxicity. It is simply unacceptable to test 

every single member of these two groups of substances in lethal bird tests. 
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EPA Response: As of July 1, 2008, the CFR 40 Part 158 pesticide data requirements 

now include avian acute oral data for one passerine species and either a waterfowl or an 

upland game species for outdoor end-use pesticides for all new federal actions (72 FR 

60957, dated October 26, 2007). Additional avian acute oral toxicity data for passerine 

species are intended to provide information to assess differential sensitivity on a 

chemical-specific basis, determine whether assumptions of allometric relationships can 

be confidently applied to chemical classes that have not been tested, and to include a 

taxonomic group of avian wildlife that is highly represented in most pesticide use areas 

and may potentially exhibit differences in metabolic rate, physiology, and toxicokinetics 

from the currently tested waterfowl and upland game test species. 

Only a small pesticide toxicity data set is available for passerine species of birds. 

Currently, no acceptable avian acute oral data with a passerine species have been 

submitted to the Agency for pyrethrins or any pyrethroid, including the six pyrethroids 

mentioned in the public comment (allethrin, cypermethrin, metofluthrin, resmethrin, 

tefluthrin and tetramethrin). Furthermore, a recent study by Addy-Orduna et al. (2011)2

indicated that some passerine species may be up to 13X more sensitive than some nonpasserine species to formulated beta-cyfluthrin . As additional information on the toxicity 

of this class of insecticides to passerine species becomes available, options for bridging 

toxicity data for additional passerine species could be considered. 

MGK Comment: In addition, as a member of the Residential Exposure Joint Venture (REJV), 

the original survey database, and the new one just getting underway, will provide highly refined 

use and usage information for consumer products containing pyrethrins. We strongly urge the 

Agency to use the surveys not only for Human Health risk assessments, but also the surveys can 

be mined for detailed information that can refine ecological risk assessments for outdoor 

products. 

EPA Response: EPA looks forward to reviewing revised REJV survey to inform both 

human health and ecological risk assessments when that survey data is submitted to the 

Agency. 

Comments Related to the Human Health Risk Scoping Document

MGK Comment: With respect to the uncertainty factor of 1000 for the short-term and 

intermediate-term inhalation endpoints related to respiratory tract lesions, we disagree with the 

Agency’s position on metaplasia. A number of research studies on the respiratory tract provide 

evidence that a wide variety of factors (including chemical exposure) can bring about the 

histopathological transformation of squamous metaplasia of the larynx. Other factors that 

suggest squamous metaplasia in the larynx of rats should not be viewed as a toxicological 

 

2

 Addy-Orduna, LM, Zaccagnini, M, Canavelli, SB, Mineau, P. 2011. Formulated Beta-Cyfluthrin ShowsWide 

Divergence in Toxicity among Bird Species. J. Toxicol. vol. 2011, Article ID 803451, 10 pp. 
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response, but rather an adaptive one. We provided more detail information during the 

Reregistration process and plan to revisit this issue during the Registration Review process. 

EPA Response: With respect to the short-term inhalation endpoint, EPA points out that it 

is based on tremors, labored breathing, hyperactivity, secretory signs, matted coat, and 

decreased body weight/body weight gain, which were observed during the first few 

weeks of the subchronic inhalation study. The intermediate-term inhalation endpoint is 

not based solely on metaplasia. The LOAEL in the subchronic inhalation study is based 

on hypertrophy/hyperplasia in the mucosal seromucous glands of the larynx, 

pseudostratified ciliated/nonciliated columnar epithelial hyperkeratosis of the larynx 

(both sexes), goblet cell hyperplasia in the nasopharynx and nasoturbinates (males), and 

epithelial intracytoplasmic eosinophilic material in the nasoturbinates, which were 

observed at all dose levels at the end of the study.

MGK Comment: EPA has made a gross error in the hazard characterization section and quoted 

the incorrect cancer classification for pyrethrins. After review of the mechanism of action data 

of the PJV, in the EPA report “PYRETHRINS: Fourth Report of the Cancer Assessment Review 

Committee”, TXR No.: 0054822, dated February 14, 2008, EPA reclassified pyrethrins as “Not 

Likely to be Carcinogenic to Humans” at doses that do not cause a mitogenic response in the 

liver/cell proliferation.

EPA Response: The Agency acknowledges this error. MGK Company is correct in 

pointing out that the cancer classification for pyrethrins is “Not Likely to be 

Carcinogenic to Humans” at doses that do not cause a mitogenic response in the liver/cell 

proliferation. 

MGK Comment: The large number of incidents reported in the time period of 2006 to 2011, is 

misleading with respect to products containing pyrethrins. Many of the products with pyrethrins 

also contain more toxic residual pyrethroids which are more likely to have caused effects, if they 

were attributable to the pesticide exposure (many reportable incidents are deemed unrelated to 

exposure to the product.) The PJV is mid way through a 5 year product stewardship program 

with the Agency providing information to clarify any role pyrethrins may have in adverse 

effects, particularly possible allergic reactions. So far, the results indicate many fewer effects 

directly related to pyrethrins exposure. This program is further described in bullet three in the 

EPA document. 

EPA Response: EPA acknowledges that when an incident involves more than one 

pesticide, it is difficult to determine which effects are attributed to the pesticide being 

considered. However, because pyrethrins are usually co-formulated with other active 

ingredients, and because there is about a 50-fold difference between the frequency of 

incidents involving pyrethrins alone versus pyrethrins and other chemicals, it is important 

to attend to the incidents involving multiple chemicals. Consequently, based on the 
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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. EPA agrees it will be important to consider Pyrethrins 

Joint Venture (PJV) product stewardship program during the preliminary risk assessment 

phase of Registration Review.

MGK Comment: With respect to the Immunotoxicity study requirement, MGK points EPA to 

the ongoing effort between CropLife America and EPA OPP’s Health Effects Division review of 

all of the existing immunotoxicity data submitted to date. This effort brings out the fact that no 

toxicological endpoints have changed or been further informed by this data requirement. We 

look forward to EPA’s review and further dialog in hopes that clear criteria for waiving out of 

the data requirement can be identified to prevent the unnecessary sacrifice of animals from 

unnecessary studies.

EPA Response: OPP is conducting an independent retrospective analysis of more than 

150 immunotoxicity studies submitted to Agency. Preliminary findings of OPP’s 

retrospective analysis suggest that immunotoxicity studies have not yet provided lower 

PoDs than are selected from other guideline experimental toxicology studies and thus, so 

far, immunotoxicity studies would not have impacted the Agency’s risk assessments. The 

OPP retrospective analysis is anticipated to be completed in the summer of 2012. In the 

interim, EPA recommends that the immunotoxicity continue to be required for 

registration and registration review chemicals.

PCRM Comment: The Physician’s Committee for Responsible Medicine raised two studies that 

may be relevant for bridging pyrethroid (and in this case, pyrethrins) data in regard to 

immunotoxicology. The two citations for the two studies are as follows: 

• Zhang Y et al. 2010. Immunotoxicity of pyrethroid metabolites in an in vitro model. 

Environ Toxicol Chem. Nov;29(11):2505-10. 

• Agency for Toxic Substances and Disease Registry, Public Health Service, U.S. 

Department of Health. and Human Services. EPA Toxicological Profile for Pyrethrins 

and Pyrethroids. Pg. 77. September 2003. 

EPA Response: EPA will investigate these studies as part of the toxicological 

evaluation of pyrethrins conducted for Registration Review. 

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. 
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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:

Environmental Fate Data Gaps

o GLN 835.4100 Aerobic Soil Metabolism3

o GLN 835.4200 Anaerobic Soil Metabolism4

o GLN 835.4300 Aerobic Aquatic Metabolism5

o GLN 835.4400 Anaerobic Aquatic Metabolism6

o GLN 835.6100 Analytical method and associated independent laboratory 

validations in soil 

 

3

 Conduct studies in three different soil types; for metabolism studies, domestic soils are preferred. 4

 Conduct studies in four different soils; for metabolism studies, domestic soils are preferred. 5

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

6

 Conduct studies with two water/sediment systems, with one of the sediment systems from estuarine/marine origin. 
10 

o GLN 835.6200 Analytical method and associated independent laboratory 

validations in water and sediment 

Ecological Toxicity Data Gaps

o GLN 850.1010 Aquatic toxicity freshwater invertebrates (Hyalella azteca) – 

water column7

o GLN 850.2100 Avian Oral Toxicity, Passerine 

o GLN 850.2300 Avian Reproduction, Quail/Duck8

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 

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 

 

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Refer to 850.1020 Gammarid Acute Toxicity Test as a basis for study development for Aquatic Toxicity Freshwater 

Invertebrates (Hyalella azteca) – water column. 8

 Tests are recommended for the technical product with waterfowl and an upland game bird species. 
11 

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. 

• 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. 
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• 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 and are 

summarized in the DAT Call-Ins 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. 

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, 
13 

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/. 
14 

Timeline

 

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

below in Table 1. 

Table 1. Projected Pyrethrins Registration Review Timeline9

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 

Next Steps

The Agency plans to issue a Data Call-in (DCI) for pyrethrins in 2013. The information received 

in response to this DCI will be used to conduct the planned human health, ecological risk, and 

endangered species assessments for pyrethrins. 

Summary of Data Needs for the Registration Review of Pyrethrins

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 

 

9

 Any changes in the cumulative risk from the pyrethroid class of insecticides may impact this time estimate. 
15 

o GLN 860.1850 Confined accumulation in rotational crops 

o GLN 875.2500 Inhalation exposure – residential misting systems 

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 

o GLN 875.1700 Product use information (outdoor 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) 

 

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. 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 dilutus). 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. 
16 

o GLN 875.2500 Inhalation exposure - post application (trigger pump 

sprayer) 

o GLN 875.2500 Inhalation exposure – post application (loading and 

application of dust) 

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 

850.1010 Aquatic toxicity freshwater invertebrates 14 TGAI 12 

850.2100 Avian Oral Toxicity, Passerine TGAI 12 

850.2300 Avian Reproduction - Quail/Duck TGAI 24 

850.4100 Seedling Emergence, Tier II TEP 12 

850.4250 Vegetative Vigor, Tier II TEP 12 

870.7800 Immunotoxicity TGAI 12 

 

 

14Refer to 850.1020 Gammarid Acute Toxicity Test as a basis for study development for Aquatic Toxicity 

Freshwater Invertebrates (Hyalella azteca) – water column.