settings. Based on the current use profile, exposures to pyrethrins can be expected to occur via 

the dietary (food and drinking water), residential (handler and postapplication), and occupational 

(handler and postapplication) routes. 

The 2006 risk assessment, conducted for the Reregistration Eligibility Decision (C. Olinger, 

D326648, 3/16/06) addressed exposures and risks associated with the dietary, drinking water, 

occupational, and residential uses of pyrethrins. Based on this, acute and chronic dietary and 

drinking water aggregate exposures for pyrethrins did not present risk estimates of concern. The 

residential exposure assessment conducted for the Reregistration Eligibility Decision (RED) 

determined that residential handler exposure scenarios showed no risk estimates of concern. All 

of the short-term occupational handler exposure scenarios assessed showed no risk estimates of 

concern; several intermediate-term occupational handler scenarios involving wettable powders 

showed risk estimates of concern. Several residential post-application exposure scenarios and 

occupational exposure scenarios assessed presented risk estimates of concern. PRD 

implemented mitigation measures in the form of use pattern limitations and confirmatory 

exposure and efficacy data to address these residential and occupational risks. Since the RED, 

HED has completed assessments for pyrethrins used to treat in-home bedbug infestations and to 

directly treat pets. These non-occupational assessments did not identify risk estimates of concern. 

HED’s scoping document conclusions are as follows: 

1) 1) A number of residue chemistry requirements identified in the RED have not been 

submitted. The outstanding data must be submitted for registration review. 

2) For hazard assessment, an immunotoxicity study is required under 40 CFR Part 158 as a 

part of the new data requirements for registration of a pesticide (food and non-food uses). 

This study has not been submitted and is required to support registration review. A 

developmental thyroid assay, which was required in the 2006 risk assessment, has not 

been submitted and is required to support registration review. In lieu of conducting a 

DNT study for pyrethrins, which was required in the 2006 risk assessment, the Registrant 

may instead choose to cite the six previously submitted DNT studies for pyrethroids to 

fulfill this data gap. 

3) Several residential/occupational exposure studies requested in the RED have not been 

submitted and are necessary to address outstanding risk concerns identified in the RED. 

4) Upon receipt of outstanding chemistry data, HED will determine if a new dietary risk 

assessment is required. Updates to dietary risk assessment methodologies (updated 

consumption data, and utilization of the newest version of Dietary Exposure Evaluation 

Model software with the Food Commodity Intake Database (DEEM-FCID) may also 

impact the dietary risk assessment. 

5) The residential exposure assessment was adequate but should be updated to reflect 

updates to the standard operating procedures that will be implemented in the near future. 

6) The occupational exposure assessment was adequate but should be updated to reflect 

current standard operating procedures. The outstanding inhalation fogger data must be 

submitted for registration review. 

7) The aggregate risk assessment was adequate but may need to be updated to incorporate 

any changes to dietary and/or residential exposure assessments. 

Page 2 of 25 
Introduction 

HED has evaluated the existing human health risk assessments for the insecticides known 

collectively as the pyrethrins to determine whether sufficient data are available and whether a 

new human health risk assessment is needed to support Registration Review. HED has 

considered the most recent risk assessments for pyrethrins, updates to its toxicity, exposure and 

usage databases, and current Agency science policies and risk assessment methods. The risk 

assessment used to support the 2006 Reregistration Eligibility Decision (RED) and several 

addendum memoranda (e.g., pet collar rate corrections, new use actions for bedbug treatments) 

were the primary sources for this evaluation. 

Throughout this document the individual pyrethrin compounds are referred to by the common 

names of the acid (in lower case e.g. pyrethrin, cinerin, and jasmolin) followed by a number in 

Arabic (1 or 2). If common names are plural, but not followed by a numerical designation, then it 

refers to both I and II forms. If the term Pyrethrins is used, and followed by a numerical 

designation, then the term refers to all of the isomers of that number in the pyrethrum extract 

(e.g. Pyrethrins I includes pyrethrin I, cinerin I, and jasmolin I). Both “pyrethrins” and 

“pyrethrum” are used as a term for insecticidal extract of the Chrysanthemum cinerarieaefolium 

plant, and are used in this document as a term to denote all six active ingredients collectively. 

Use Profile 

Pyrethrins have numerous and varied commercial and residential applications, are available in a 

broad range of formulations, and are applied by a wide variety of application methods. 

Pyrethrins formulations include a variety of formulated intermediates, emulsifiable concentrates, 

and soluble concentrates. Formulated products generally contain 0.25 - 0.5 % active ingredients. 

pproximately 200,000 pounds are sold every year, with ~90% being used in non-agricultural 

ites. 

A

s

Pyrethrins have a wide use pattern including (i) pre-harvest and post-harvest uses on many 

agricultural crops; (ii) direct and indirect treatments of livestock animals and premises; (iii) 

treatments of commercial and industrial facilities and storage areas where raw and processed 

food/feed commodities are stored or processed; (iv) mosquito abatement areas including aquatic 

areas; (v) structural treatments; and (vi) treatment of domestic animals. Pyrethrins are used with 

a variety of other insecticides and they are typically formulated with the synergist piperonyl 

butoxide or synthetic pyrethroids. Pyrethrins currently have 70 tolerances (40 CFR 180.128 & 

180.905) in/on various crop and livestock food commodities. Pyrethrins are used residentially to 

control insects both inside the home and outside on gardens, lawns and ornamentals, patios, and 

other outdoor structures, and can be directly applied to pets. 

The main active ingredients in pyrethrins extracts are pyrethrin I and pyrethrin II plus smaller 

amounts of the related cinerin I and II and jasmolin I and II. The chemical names and structures 

of these ingredients may be found in the chemical identity table in Appendix A. 

Page 3 of 25 
Hazard Identification/Toxicology 

Pyrethrins cause neurotoxicity in insects and mammals by the modulation of nerve axon sodium 

channels. Pyrethrins interfere with the ability of the nervous system to relay nerve transmissions, 

potentially resulting in tremors, convulsions, salivation, and other clinical effects at high doses. 

The toxicity database for pyrethrins is incomplete at the present time; data gaps include an 

immunotoxicity study, a developmental thyroid assay, and fulfillment of the data requirement for 

a DNT. The immunotoxicity study in rats, which is required in accordance with new data 

requirements for conventional pesticide registration (40 CFR Part 158), has not been submitted 

and is considered to be a data gap. Although available hematology, lymphoid organ weights, and 

histopathology data on pyrethrins do not suggest any immunotoxic effects, these endpoints alone 

are insufficient to predict immunotoxicity. As part of the 2006 risk assessment (D326648), a 

developmental thyroid study ("Guidance for Thyroid Assays in Pregnant Animals, Fetuses and 

Postnatal Animals, and Adult Animals") was required due to thyroid effects observed following 

chronic exposure. This request stems from concerns regarding the possible impact of 

perturbations of thyroid function on the development of the young. A developmental thyroid 

assay has not been submitted to the Agency to date and is considered a data gap. Also in the 

2006 risk assessment (D326648), the Agency requested that a DNT study be conducted on rats 

with pyrethrins. This request was based on evidence of neuropathology in rats following acute 

exposure in the acute neurotoxicity study. Increased incidence of neurobehavioral effects in rats 

and mice following short-term and chronic exposure further supported this request. However, 

based on the Agency’s review of existing pyrethrins/pyrethroid data, EPA has come to the 

conclusion that the DNT is not a particularly sensitive study for comparing the sensitivity of 

young and adult animals to pyrethrins/pyrethroids. In lieu of conducting a DNT study for 

pyrethrins, the Agency has determined that the registrants may instead choose to cite the six 

previously submitted DNT studies for pyrethroids (Keigwin, Sept 4, 2009) to fulfill this data gap. 

The science supporting this conclusion can be found in “Pyrethroids: Evaluation of Data from 

DNTs & Consideration of Comparative Sensitivity1” (E. Scollon, 1/20/10, D371723). 

Regarding the new data requirement for a subchronic neurotoxicity study for conventional 

pesticide registration, pyrethrins are acutely neurotoxic in mammals and data demonstrate that 

rapid clearance from the body prevents bioaccumulation and, therefore, repeated dose studies are 

actually a series of acute doses. Since there was an acute neurotoxicity study on pyrethrins, 

which identifies a clear NOAEL and LOAEL, a subchronic neurotoxicity study on pyrethrins 

would not be expected to identify a different endpoint or effect level than is already available. 

Therefore, a subchronic neurotoxicity study is not required for pyrethrins at this time. 

In the acute lethality studies that assess primarily mortality, pyrethrins are not acutely toxic by 

the oral, dermal, or inhalation routes of exposure. Pyrethrins are moderately irritating to the eyes, 

minimally irritating to the skin, and are not a skin sensitizer. 

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 

 

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

Page 4 of 25 
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. 

There is suggestive evidence that pyrethrins are carcinogenic based on weight-of-the-evidence 

considerations. The finding of thyroid tumors in rats of both sexes was not of concern for 

humans based on the mode of carcinogenic action data. There was an increase in the occurrence 

of benign liver tumors only in female rats. No treatment-related increase in other tumors was 

observed in male rats, and no treatment-related increase in tumors in mice of either sex was 

observed. There was no concern for mutagenicity. Pyrethrins are classified as “Suggestive 

Evidence of Carcinogenicity, but Not Sufficient to Assess Human Carcinogenic Potential”; 

therefore a quantitative cancer risk assessment was not conducted. 

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. In further evaluating the potential for dermal exposure, no findings were identified in the 

developmental or reproduction studies that would indicate the need for a dermal risk assessment 

for pyrethrins. Since there are 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. Although there was 

evidence of increased quantitative susceptibility in the 2-generation reproduction study in rats, 

the reproductive/ offspring toxicity NOAELs and LOAELs are well characterized. Additionally, 

the relevance of the findings in the rabbit developmental toxicity study (one abortion and one full 

litter resorption) in ascribing evidence of developmental toxicity is equivocal since it is not 

uncommon for rabbits to abort/resorb their litters, and the NOAEL and LOAEL for these effects 

are well characterized. Further, since these studies (i.e., two-generation reproduction and rabbit 

developmental studies) serve as the basis for the endpoints used for risk assessment for the 

appropriate population subgroups, reduction of the FQPA factor to 1X was determined to be 

appropriate. 

Subsequent to the RED, a special Functional Observational Battery (FOB) study, which 

measured behavioral changes that are associated with the central and peripheral nervous system 

following acute oral exposure to pyrethins and pyrethroids, was published in the open literature. 

Additionally, there was evidence of age-dependent toxicity in the open literature. Juveniles 

appear to be more susceptible based on decreased metabolic capacity to detoxify 

pyrethroids/pyrethrins. The Agency recently presented this topic to a Scientific Advisory Panel 

(SAP) (July 23, 2010). Based on comments from the SAP, a conglomeration of pyrethroid 

registrants and product formulators (Council for the Advancement of Pyrethroid Human Risk 

Assessment (CAPHRA)) are conducting a series of studies to further examine the relationship 

between age and pyrethroid toxicity. Studies will include in vitro examination of pyrethroid 

interaction with rat and human voltage-gated sodium channels, development of human PBPK 

models, and in vivo behavioral testing using auditory startle in rats. The FQPA factor for 

pyrethrins will be re-evaluated during registration review following a final determination of the 

potential for increased susceptibility of infants and children to pyrethrins pesticides based on the 

results of all available data. 

Page 5 of 25 
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 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 developmental neurotoxicity (DNT) study and the 

concern for neurotoxicity resulting from exposure to pyrethrins. 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. Upon receipt of 

the outstanding toxicology data and consideration of all available data, the endpoints for risk 

assessment and all uncertainty factors will be re-evaluated during registration review to reflect 

updated data and uncertainty factor policies. 

Data Requirements

The hazard database for the pyrethrins remains incomplete. A Pyrethrins DCI (GDCI-069001-

27992) was issued in 2009 and EPA has not yet received all of the studies to satisfy the toxicity 

data requirements. The outstanding data requirements for pyrethrins are listed in the final 

section of this document. 

Conclusions

The HED Registration Review problem formulation team has re-evaluated the toxicity analysis 

conducted for the 2006 pyrethrins risk assessments based on current Agency policies. Based on 

this evaluation, the toxicity database is incomplete. Once all of the required toxicity data have 

been received and reviewed and all available data considered, the Pyrethrins Registration Review 

Team recommends that the points of departure and safety factors be reexamined and a new risk 

assessment be completed, if necessary. 

Dietary and Drinking Water Exposures 

Dietary Exposures

Pyrethrins are registered for use on most agricultural crops. Residues of the pyrethrins tend to 

stay on the plant surfaces, with little translocation to the root and other parts of the plant. Surface 

residues are vulnerable to photolysis. Pyrethrins are used in many types of indoor settings where 

food may be present, such as warehouses, grain storage areas, restaurants, and food 

manufacturing plants. Generally, the pyrethrins break down more slowly indoors than outdoors 

where the residues are prone to photolysis. 

When applied to livestock, or when livestock consume feed bearing residues of pyrethrins, little 

breakdown of the parent compound was observed in fatty matrices, such as fat, milk fat, egg 

yolk, and poultry skin. In plants, livestock, and the environment, the breakdown products of the 

pyrethrins are of less toxicological concern than the parent compound, so only the six active 

ingredients of pyrethrins are considered in the dietary assessment. 

Many residue studies were required in the RED to support tolerance reassessment and dietary 

risk assessment, including storage stability, rotational crop, crop field trial, and processing 

studies (Olinger and Deluzio, 2005). Some of these studies have been submitted, but numerous 

studies remain outstanding. HED has modified the data requirements (C. Olinger, 2009/2010, D. 

Soderberg, 2011) in response to waiver requests. Residues have been quantifiable in most field 

Page 6 of 25 
trials submitted to date, with the exception of the root and tuber vegetables. This residue profile 

was consistent with the metabolism data that indicate that residues do not translocate. 

Due to the lack of residue data in a number of commodities, HED made several conservative 

assumptions (with respect to residue levels) for some crops, but refined the dietary risk 

assessment conducted to support the RED using percent crop treated information (Deluzio, 

2004). The dietary assessment (food and water) did not indicate risk estimates of concern. In 

the period 2005-2009, the USDA Pesticide Data Program (PDP) analyzed over 64,000 fruit, 

vegetable, poultry, and pork samples for residues of pyrethrins. Only two poultry samples 

showed quantifiable residues, at 0.1 ppm; residues were below the limit of quantitation in all 

other samples. These PDP data further confirm the health protective nature of HED’s previous 

dietary risk assessment in that it overestimates dietary exposure to pyrethrins. 

Drinking Water Exposures

The Environmental Fate and Effects Division performed a Tier I drinking water assessment for 

pyrethrins in surface water and groundwater. EFED used the FIRST model for estimating the 

upper bound on the concentrations that could occur in surface-water-source drinking water, and 

the SCI-GROW model to estimate the concentrations in ground water used for drinking water. 

Parent pyrethrin I is not very persistent. When applied to soil, it is likely to remain near the 

surface and degrade relatively rapidly via photolysis and more slowly via aerobic soil 

metabolism. Parent pyrethrin is considered immobile and there is an extremely small likelihood 

of its leaching to groundwater. Pyrethrins may be applied by air and surface water could become 

contaminated through spray drift or runoff events accompanied by erosion that occur shortly 

after application. In aquatic environments, pyrethrins are moderately persistent under aerobic 

aquatic metabolism and more persistent under anaerobic aquatic metabolism. 

Since new environmental fate data was required for pyrethrins, EFED has indicated that a new 

drinking water assessment should be completed.

Data Requirements

The database for the dietary exposure assessment remains incomplete in numerous 

commodities. A Pyrethrins DCI (GDCI-069001-27992) was issued in 2009 and EPA has not yet 

received all of the studies to satisy the residue chemistry data requirements. The outstanding 

data requirements for pyrethrins are listed in the final section of this document. 

Conclusions

A new dietary risk assessment may be necessary once all of the residue data have been received 

and reviewed. This assessment will use PDP data along with the new crop field trials for those 

commodities not analyzed by PDP. In addition, HED will reassess all tolerances using the new 

crop field trial and processing studies. HED will re-evaluate the need for poultry tolerances once 

all of the magnitude of residue data on poultry feed items have been received and reviewed. 

Page 7 of 25 
Also, an updated drinking water assessment from EFED may dictate further changes to the 

existing dietary or aggregate risk assessments. 

Residential Exposure 

Residential scenarios assessed include short-term and intermediate term exposures of handlers 

(mixers, loaders, applicators, etc.) that occur during application oi f pyrethrins and short-term 

post-application exposure from activities in treated areas. As previously noted, dermal exposure 

was not assessed because no systemic effects were observed at the limit dose in a 21-day dermal 

toxicity study in rabbits and no findings were identified in the developmental or reproduction 

studies that would indicate a dermal hazard for pyrethrins. 

Pyrethrins are registered for residential uses as a pest control agent in homes and outdoor 

domestic structures, on gardens, lawns, and ornamentals, and direct application to household 

pets. Pyrethrin formulations include aerosol; combustible coil; dilutable concentrate; dust; 

emulsifiable concentrate; gel; impregnated packaging mat; microemulsion; microencapsulated 

(ready-to-use spray and liquid concentrate), ready-to-use liquid, pour-on (spot-on), pressurized 

dust, pressurized liquid, pressurized spray, shampoo, water-based concentrate, wettable powder, 

and towelette. They are applied by commercial and residential applicators by a wide spectrum of 

application equipment methods. These uses have been previously assessed in the Health Effects 

Division (HED) human health risk assessment for the registration eligibility decision (RED) 

(D326648). Residential scenarios assessed include mosquito abatement, turf treatment, indoor 

fogger use, pet treatment, space sprays, crack and crevice sprays, and metered release. 

In the assessments for the pyrethrins RED, there were no residential risk estimates of concern 

identified when pyrethrins are mixed, loaded, applied, or handled by homeowners. There are a 

number of residential postapplication scenarios where risk estimates of concern were identified 

and risk mitigation measures were implemented by PRD including 1) indoor broadcast 

applications, 2) indoor metered release systems, and 3) outdoor residential misting systems. 

The pyrethrins RED identified risk estimates of concern for indoor applications with metered 

release devices and outdoor residential misting systems. The Agency required data submissions 

for residential indoor metered release systems and outdoor residential misting systems for 

pyrethrins and piperonyl butoxide. That data has been submitted to the Agency and is under 

review by HED for use in future risk assessments. 

Since the RED, HED has completed assessments for pyrethrins used to treat in home bedbug 

infestations and to directly treat pets. These assessments did not identify residential risk 

estimates of concern. 

Data Requirements

The 2006 RED requested data on indoor and outdoor metered release systems, as well as some 

specific product use information. A Pyrethrins DCI (GDCI-069001-27992) was issued in 2009 

and EPA has not yet received all of the studies to satisy the residential exposure data 

requirements. The majority of the required data has already been submitted to the Agency. The 

outstanding data requirements for pyrethrins are listed in the final section of this document. 

Page 8 of 25 
Conclusions

It should also be noted that policy revisions such as anticipated modifications in the Agency 

standard operating procedures for completing residential exposure assessments could require 

revision of elements of the current exposure assessments. 

The residential exposure assessment may also be updated to incorporate any new data submitted 

by registrants or other stakeholders. 

Aggregate Risk Assessment 

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 the children’s Aggregate Risk 

Index (ARI) was calculated to be 0.96 and characterized as not of concern because the dietary 

contribution included high-end field trial data and assumed 100% percent crop treated for all but 

a few crops. 

Conclusions

A new aggregate assessment may be needed that considers the required new toxicity and residue 

data as well as any changes in the residential use pattern. 

Occupational Exposure 

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

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

labels require the use of normal work clothing for handlers with gloves and dust/mist respirators 

added for handheld fogging applications. The current Restricted-Entry Interval is 12 hours. A 

number of occupational handler scenarios were assessed. The scenarios assessed that indicated 

potential risk concerns for occupational handlers were those using wettable powder formulations 

over the intermediate-term exposure duration. The RED mitigation measures included water 

soluble packaging for all wettable powder formulations. The addition of this mitigation 

addresses the identified risk concerns. 

 Handlers applying with handheld foggers were not assessed for the pyrethrins RED due to lack 

of use and application information; the RED required data on air concentrations and residues as a 

result of handheld fogging applications. The Non-Dietary Exposure Task Force is currently 

working on a data submission to the Agency to address these exposure scenarios in future risk 

assessments. 

A revised occupational risk assessment may be required if endpoints or points of departure 

change and/or because updated monitoring data are being developed for pertinent occupational 

handler exposures and additional handler exposure scenarios also need to be addressed that were 

not included in previous assessments. Additionally, a revised risk assessment will be needed to 

address possible exposure to workers doing activities in previously treated areas (i.e., postapplication exposure). The existing policy on farmworker activities was recently revised and 

includes either updated values for quantitatively evaluating these exposures or it will provide a 

more definitive qualitative rationale for not conducting a quantitative assessment. 

Page 9 of 25 
After the Non-Dietary Exposure Task Force (NDETF) submits the required studies on 

occupational fogger applications, adequate data will be available to assess all the occupational 

exposure scenarios for the registered uses of pyrethrins. Policy revisions, such as updates to the 

Occupational Pesticide Handler Exposure Data2

 (OPHED), could cause elements of the current 

exposure assessments to be revised (e.g., changes in transfer coefficients for field workers and 

unit exposures for handlers). Also, additional changes in other risk assessment policies related to 

spray-drift, worker protection and volatilization of pesticides may dictate further changes to the 

existing risk assessment. 

Data Requirements

The 2006 RED requested data on indoor and outdoor-metered release systems and handheld 

fogging applications. A Pyrethrins DCI (GDCI-069001-27992) was issued in 2009 and EPA has 

not yet received all of the studies to satisy the applicator exposure data requirements. The 

majority of the required data has already been submitted to the Agency. The outstanding data 

requirements for pyrethrins are listed in the final section of this document. 

Conclusions

The occupational exposure assessment 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 PODs for the pyrethrins. 

Public Health and Pesticide Epidemiology Data 

An updated incident report was recently conducted. The OPP Incident Data System (IDS) was 

utilized for pesticide incident data on the active ingredient pyrethrins (PC Code 069001). 

Additionally, if there are Agricultural Health Study (AHS) findings relevant to a particular 

pesticide, they are considered in the problem formulation/scoping document. Pyrethrins are not 

included in the AHS. 

For the main IDS, from January 1, 2006 to June 6, 2011, there are 13 exposures reported for 

single chemical only in the database, and 803 additional exposures that involved more than one 

chemical. During the scoping phase of Registration Review, the higher severity exposures (those 

resulting in fatal or major outcomes) are considered in more detail. Additionally, as described 

above, incidents involving one pesticide are typically focused on because they are considered to 

provide more certain information about the potential effects of the particular pesticide. However, 

because pyrethrins are usually co-formulated with other active ingredients, and because there 

was 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 in this case. 

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 

 

2

 http://www.epa.gov/opp00001/science/handler-exposure-data.html 

Page 10 of 25 
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/allergies3. 

During the Reregistration of pyrethrins, EPA required the Pyrethrins Joint Venture (PJV), an 

industry task force, to institute 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 to better understand the cause of the incidents 

with pyrethrins.4

In general, a relatively high frequency of incidents has been reported involving pyrethrins. Most 

of these incidents were of low severity. Additional human incident data may warrant further 

analysis for the risk assessment and/or risk management of pyrethrins. The Agency will 

continue to monitor the incident information and if a concern is triggered, additional analysis 

will be included in the risk assessment. During the preliminary risk assessment phase of 

Registration Review, the HED risk assessment team will revisit pyrethrins incident data 

(including an analysis of the PJV) and if a concern is triggered, additional analysis will be 

included in the risk assessment. 

Tolerance Assessment and International Harmonization 

Tolerances are established for residues of pyrethrins in or on numerous food and feed 

commodities and are listed in 40 CFR 180.128 and 180.905(a)(6). A summary of the existing 

tolerances may be found in Appendix B, as well as international tolerances. Many tolerances are 

harmonized with Canada Maximum Residue Limits (MRLs) with respect to residue level. There 

are many differences between the US and Codex MRLs with respect to residue definition and 

residue level. Mexico adopts US tolerances and/or Codex MRLs for its export purposes. 

Some field trial data required in the RED remain outstanding. Once these data have been 

received modifications to tolerance levels will be needed. In addition, the residue definition 

should be modified in accordance with the guidance issued in 2009 (S. Knizner, 5/27/09) and 

with other international standards. The registrants are encouraged to work with the Agency and 

international regulatory authorities to develop a consistent approach for the residue definition.

In registration review, HED will reconsider the U.S. tolerances and will harmonize them with 

Codex MRLs when the data warrant harmonization. 

Environmental Justice 

Potential areas of environmental justice concerns, to the extent possible, were considered in the 

human-health risk assessment, in accordance with U.S. Executive Order 12898, “Federal Actions 

to Address Environmental Justice in Minority Populations and Low-Income Populations,” 

(http://www.hss.energy.gov/nuclearsafety/env/guidance/justice/eo12898.pdf). The OPP 

typically considers the highest potential exposures from the legal use of a pesticide when 

 

3

 http://www.epa.gov/oppsrrd1/reevaluation/pyrethrins-pyrethroids-asthma-allergy-9-18-09.pdf 4

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

Page 11 of 25 
conducting human-health risk assessments, including, but not limited to, people who obtain 

drinking water from sources near agricultural areas, the variability of diets within the U.S., and 

people who might be exposed when harvesting crops. Should these highest exposures indicate 

potential risk estimates of concern, OPP further refines the risk assessments to ensure that the 

risk estimates are based on the best available information. 

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 that 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 reregistration decision, 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). 

As required under FFDCA section 408(p), 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 the Agency’s website: 

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

Cumulative Risk Assessments 

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 

Page 12 of 25 
pyrethroid/pyrethrin common mechanism group (http://www.regulations.gov; EPA-HQ-OPP2008-0489-0006). 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. 

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. 

Conclusions/Future Actions Needed 

The actions needed in the future Registration Review for pyrethrins are listed below. 

Hazard Identification and Endpoint Selection

Pyrethrins are axonic toxicants, and there was evidence of neurotoxicity following exposure to 

pyrethrins, based on clinical signs (tremors, convulsions, decreased motor activity, excessive 

salivation, head arched backward) and neuropathology in acute, developmental, reproductive 

studies submitted to the Agency. To date, EPA has not received these hazard-related studies to 

satisfy the 2009 Pyrethrins DCI (GDCI-069001-27992): 

• Although the data gap of a developmental neurotoxicity study (DNT) (GLN 870.6300) 

has not been satisfied, as discussed above, the pyrethrins registrants plan to satisfy the 

data requirement by citing the six previously submitted DNT studies for pyrethroids to 

fulfill this data gap/requirement. 

• Additionally, the previously required developmental thyroid assay has not been submitted 

to the Agency. In future human health risk assessments, the Agency may use a database 

uncertainty factor to account for any missing data. 

The following data gaps/study requirements are new and have not been previously 

required by the Agency:  

• Under the revised 40 CFR Part 158 Toxicology Data Requirements, an immunotoxicity 

study is required for all pesticides. The required study rationale is included in Appendix 

C. However, since the results of the available toxicity studies provide no evidence for 

immunotoxicity following pyrethrins exposure, the Agency may consider a waiver for 

Page 13 of 25 
this data requirement provided the necessary information to perform an immunotoxicity 

evaluation is submitted as part of the waiver request. 

Dietary Exposure and Risk

The dietary risk assessment should be updated to reflect current policies and SOPs and to 

incorporate outstanding data requirements. To date, EPA has not received these dietary-related 

studies to satisfy the 2009 Pyrethrins DCI (GDCI-069001-27992): 

• Storage Stability Data (GLN 860.1380) on oilseeds, non-oily grains, and root crops 

• Crop Field Trials (GLN 860.1500) See Appendix D for the outstanding required field 

trial data5

. 

• Processed Food/Feed data (GLN 860.1520); Processing studies were required in the DCI 

for the following commodities: apple, barley, cacao, coconut, coffee, corn, cotton, fig, 

flax, oat, peanut, pineapple, plum, rice, rye, safflower, sorghum, soybean, sugarcane, 

sunflower, tea, and wheat. 

• Confined Accumulation in Rotational Crops (GLN 860.1850) 

 

Residential Exposure and Risk

The residential risk assessment may need to be updated to reflect any changes in endpoints or 

points of departure, changes in current policies and the upcoming revisions to the residential 

SOPs as well as incorporating any new data submissions. 

The data requirements, originally identified in the 2009 Pyrethrins DCI (GDCI-069001-27992), 

are intended to inform post-application exposure assessment and remain outstanding: 

• Product Use Information (GLN 875.1700) on metered release devices 

Aggregate Exposure and Risk

The existing aggregate exposure assessment need to be updated to reflect current policies and 

SOPs and to incorporate any changes to the dietary and/or residential exposure assessments. 

Occupational Exposure and Risk

The occupational risk assessment should be updated to reflect current policies and SOPs (e.g., 

new unit exposure data) and to incorporate the outstanding data requirements: 

These data requirements (relating to handheld foggers), originally identified in the 2009 

Pyrethrins DCI (GDCI-069001-27992), remain outstanding: 

• Inhalation Indoor Exposure (GLN 875.1400) 

Incident Report

The Agency will continue to monitor the incident information related to pyrethrins and if a 

concern is triggered, additional analysis will be included in the risk assessment. 

 

5

 Additional detail is available in the memos “Pyrethrins. Response to Comments on Residue Data Requirements”; 

C. Olinger (D366246, 10/27/09) & “Pyrethrins. Response to a “Proposal to Further Reduce Pre-Harvest Residue 

Data Requirements Due to Low Usage of Pyrethrins” and a Request for Extension on Time to Submit DCI Studies 

by 2-3 Years”; D. Soderberg (D392195, 08/31/11). 

Page 14 of 25 
References 

Pyrethrins: DNT DCI Letter for Pyrethrins. Keigwin, 9/04/09 

Pyrethrins: Revised Human Health Risk Assessment for the Reregistration Eligibility Decision, 

C. Olinger (D326648, 03/16/06) 

Pyrethrins: Revised Human Health Risk Assessment for the Reregistration Eligibility Decision, 

C. Olinger (D321641, 09/14/05) 

Pyrethrins Review of Human Incidents. Sarah Winfield (D392811, 8/11/11) 

Tier I Estimated Drinking Water Concentrations of Pyrethrin and Derivatives for use in Human 

Health Risk Assessment, S. Dutta, 8/19/04, DP Barcode D295750 

Pyrethrins. Request for Waiver of Processing Studies, C. Olinger (D375958, 5/11/10) 

Pyrethrins. Response to Comments on Residue Data Requirements, C. Olinger (D366246, 

10/27/09) 

Pyrethrins. Response to a “Proposal to Further Reduce Pre-Harvest Residue Data Requirements 

Due to Low Usage of Pyrethrins” and a Request for Extension on Time to Submit DCI Studies 

by 2-3 Years. (D. Soderberg, D392195, 08/31/11) 

Pyrethrins. Revised Residue Chemistry Considerations for Reregistration Eligibility Decision, 

C. Olinger/J. Deluzio (D318633, 9/8/05). 

Pyrethrins. Acute and Chronic Dietary Exposure Assessment for Reregistration Eligibility 

Decision Document, J. Deluzio (D295748, 12/20/04) 

Pyrethrins: Human Health Aggregate Risk Assessment to Account for Pet Spray Use Rate 

Correction, T. Dole, (01/24/08) 

Pyrethrin. Occupational and Residential Exposure Assessment for the Use of a Pyrethrin Product 

for Bed Bug Treatment. A. LaMay (03/28/11) 

Draft Science Policy Paper for the Proposed Common Mechanism Grouping for the Pyrethrins 

and Synthetic Pyrethroids, A. Lowit, E. Scollan (D381210, 06/30/11) 

Re-evaluation of the FQPA Safety Factor for Pyrethroid Pesticides, A. Lowit, E. Scollan 

(D381210, 06/30/11) 

Pyrethroid Cumulative Risk Assessment, D. Davis, et. al (D394576, 10/05/11) 

Page 15 of 25 
Appendix A: Chemical Identity 

Pyrethrins is the collective name of the insecticidal active ingredients present in pyrethrum 

extracts which are obtained from the dried and ground flowers of the pyrethrum plant, 

Chrysanthemum cinerariaefolium. The CAS Registry No. for the mixture is 8003-34-7. 

Currently, food/feed uses are only registered for products under PC code 069001, mixed esters of 

(+)-trans-chrysanthemic acid and (+)-pyrethroic acid. The nomenclature of the individual 

pyrethrins active ingredients is presented below in Table 1. The physicochemical properties of 

the refined pyrethrins extracts (TGAI) are listed in Table 2. 

TABLE 1. Pyrethrins Nomenclature. 

Chemical Structure 

Common name Pyrethrin I or Pyrethrin 1 

Molecular Formula C21H28O3

Molecular Weight 328.4 

IUPAC name (Z)-(S)-2-methyl-4-oxo-3-(penta-2,4-dienyl)cyclopent-2-enyl (1R,3R)-2,2-

dimethyl-3-(2-methylprop-1-enyl)cyclopropanecarboxylate 

CAS name (1S)-2-methyl-4-oxo-3-(2Z)-2,4-pentadienylcyclopenten-1-yl (1R,3R)-2,2-

dimethyl-3-(2-methyl-1-propenyl)cyclopropanecarboxylate 

CAS # 121-21-1 

Common name Pyrethrin II or Pyrethrin 2 

Molecular Formula C22H28O5

Molecular Weight 372.4 

IUPAC name (Z)-(S)-2-methyl-4-oxo-3-(penta-2,4-dienyl)cyclopent-2-enyl (E)-(1R,3R)-3-(2-

methoxycarbonylprop-1-enyl)-2,2-dimethylcyclopropane-carboxylate 

CAS name (1S)-2-methyl-4-oxo-3-(2Z)-2,4-pentadienyl-2-cyclopenten-1-yl (1R,3R)-3-[(1E)-

3-methoxy-2-methyl-3-oxo-1-propenyl]-2,2-dimethylcyclo-propanecarboxylate 

CAS # 121-29-9 

Common name Cinerin I or Cinerin 1 

Molecular Formula C20H28O3

Molecular Weight 316.4 

O

R2

O

O

R1

CH3

3

CH

3

CH

3

CH

Pyrethrin I: R1 = CH 3; R2 = CH 2CH=CHCH=CH2

Pyrethrin II: R1 = COOCH 3; R2 = CH 2CH=CHCH=CH2

Cinerin I: R1 = CH 3; R2 = CH 2CH=CH3

Cinerin II: R1 = COOCH 3; R2 = CH 2CH=CH3

Jasmolin I: R1 = CH 3; R2 = CH 2CH=CHCHCH3

Jasmolin II: R1 = COOCH 3; R2 = CH 2CH=CHCHCH3

Page 16 of 25 
TABLE 1. Pyrethrins Nomenclature. 

IUPAC name (Z)-(S)-3-(but-2-enyl)-2-methyl-4-oxocyclopent-2-enyl (1R,3R)-2,2-dimethyl-3-

(2-methylprop-1-enyl)cyclopropanecarboxylate 

CAS name (1S)-3-(2Z)-2-butenyl-2-methyl-4-oxo-2-cyclopenten-1-yl (1R,3R)-2,2-dimethyl3-(2-methyl-1-propenyl)cyclopropanecarboxylate 

CAS # 25402-06-6 

Common name Cinerin II or Cinerin 2 

Molecular Formula C21H28O5

Molecular Weight 360.4 

IUPAC name (Z)-(S)-3-(but-2-enyl)-2-methyl-4-oxocyclopent-2-enyl (E)-(1R,3R)-3-(2-

methoxycarbonylprop-1-enyl)-2,2-dimethylcyclopropanecarboxylate 

CAS name (1S)-3-(2Z)-2-butenyl-2-methyl-4-oxo-2-cyclopenten-1-yl (1R,3R)-3-[(1E)-3-

methoxy-2-methyl-3-oxo-1-propenyl]-2,2-dimethylcyclopropanecarboxylate 

CAS # 121-20-0 

Common name Jasmolin I or Jasmolin 1 

Molecular Formula C21H30O3

Molecular Weight 328.4 

IUPAC name (Z)-(S)-2-methyl-4-oxo-3-(pent-2-enyl)cyclopent-2-enyl (1R,3R)-2,2-dimethyl-3-

(2-methylprop-1-enyl)cyclopropanecarboxylate 

CAS name (1S)-2-methyl-4-oxo-3-(2Z)-2-pentenyl-2-cyclopenten-1-yl (1R,3R)-2,2-

dimethyl-3-(2-methyl-1-propenyl)cyclopropanecarboxylate 

CAS # 4466-14-2 

Common name Jasmolin II or Jasmolin 2 

Molecular Formula C22H30O5

Molecular Weight 374.4 

IUPAC name (Z)-(S)-2-methyl-4-oxo-3-(pent-2-enyl)cyclopent-2-enyl (E)-(1R,3R)-3-(2-

methoxycarbonylprop-1-enyl)-2,2-dimethylcyclopropanecarboxylate 

CAS name (1S)-2-methyl-4-oxo-3-(2Z)-2-pentenyl-2-cyclopenten-1-yl (1R,3R)-3-[(1E)-3-

methoxy-2-methyl-3-oxo-1-propenyl]-2,2-dimethylcyclopropanecarboxylate 

CAS # 1172-63-0 

TABLE 2. Physicochemical Properties of Refined Pyrethrins (TGAI). 

Parameter Value Reference 

Boiling point Pyrethrin 1 = 146-148 C at 2 x 10-3 Torr 

Pyrethrin 2 = 196-198 C at 7 x 10-3 Torr 

Cinerin 1 = 136-138 C at 8 x 10-3 Torr 

Cinerin 2 = 182-184 C at 1 x 10-3 Torr 

RD, 10/9/90, A. Smith 

pH Not applicable because the TGAI is 

practically insoluble in water. 

Page 17 of 25 
TABLE 2. Physicochemical Properties of Refined Pyrethrins (TGAI). 

Parameter Value Reference 

Density, bulk density, or 

specific gravity 

0.982 g/mL at 20 C 

Pyrethrin 1 = 1.5242 g/mL 

Pyrethrin 2 = 1.5355 g/mL 

D172245, 1/5/93, C. Olinger 

RD, 10/9/90, A. Smith 

Water solubility <10 ppm 

Pyrethrin 1 = 0.00002 g/100 mL at 20 C 

Pyrethrin 2 = 0.00090 g/100 mL at 20 C 

DEB No. 4525, 12/9/88, M. Flood 

RD, 10/9/90, A. Smith 

Solvent solubility Completely soluble in nonpolar organic 

solvents; <0.1% in ethylene glycol 

Soluble in alcohol, petroleum ether, and 

methylene chloride 

DEB No. 4525, 12/9/88, M. Flood 

RD, 10/9/90, A. Smith 

Vapor pressure Pyrethrin 1 = 2 x 10-5 mm Hg at 25 C 

Pyrethrin 2 = 4 x 10-7 mm Hg at 25 C 

RD, 10/9/90, A. Smith 

Dissociation constant, pKa Not applicable because pyrethrins do not 

dissociate 

Octanol/water partition 

coefficient 

Pyrethrin 1 = 5.90 KOW at 25 C 

Pyrethrin 2 = 4.30 KOW at 25 C 

RD, 10/9/90, A. Smith 

UV/visible absorption spectrum Not available 

 

Page 18 of 25 
Appendix B: Summary of US and International Tolerances and Maximum Residue Limits 

Pyrethrins (PC Code 069001; 7/22/11) 

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition: 

US – See footnote 1 Canada Mexico2 Codex3 

40 CFR 180.128: 

Plant/Livestock: See footnote 1 

below 

4-hydroxy-3-methyl-2-

(2,4-pentadienyl)-2- 

cyclopenten-1-one 2,2-

dimethyl-3-(2- 

methylpropenyl)cyclop

ropanecarboxylate and 

4-hydroxy-3-methyl-2-

(2,4-pentadienyl)-2- 

cyclopenten-1-one 1-

methyl 3-carboxyα,2,2-

trimethylcyclopropanea

crylate ester 

total pyrethrins, 

calculated as the sum 

of pyrethrins 1 and 

2, cinerins 1 and 2, 

and jasmolins 1 and 

2, determined after 

calibration with the 

World Standard 

pyrethum extract. 

Commodity1 Tolerance (ppm) /Maximum Residue Limit (mg/kg) 

US Canada Mexico2 Codex3

Almond, postharvest 1.0 1.0 0.5 (*) tree nuts (Po) 

Apple, postharvest 1.0 1.0 0.2 dried fruits (Po) 

Barley, grain, postharvest 3.0 3.0 raw cereals 0.3 cereal grains (Po) 

Bean, succulent, postharvest 1.0 1.0 beans 

Birdseed, mixtures, postharvest 3.0 

Blackberry, postharvest 1.0 1.0 

Blueberry, postharvest 1.0 1.0 

Boysenberry, postharvest 1.0 1.0 

Buckwheat, grain, postharvest 3.0 3.0 raw cereals 0.3 cereal grains (Po) 

Cacao bean, roasted bean, 

postharvest 

1.0 1.0 cocoa beans 

Cattle, fat 1.0 

Cattle, meat 0.05 0.05 

Cattle, meat byproducts 0.05 0.05 

Cherry, sweet, postharvest 1.0 1.0 cherries 

Cherry, tart, postharvest 1.0 1.0 cherries 

Coconut, copra, postharvest 1.0 1.0 copra 

Corn, field, grain, postharvest 3.0 3.0 raw cereals 0.3 cereal grains (Po) 

Corn, pop, grain, postharvest 3.0 3.0 raw cereals 0.3 cereal grains (Po) 

Cotton, undelinted seed, 

postharvest 

1.0 

Crabapple, postharvest 1.0 1.0 

Currant, postharvest 1.0 1.0 

Dewberry, postharvest 1.0 1.0 

Fig, postharvest 1.0 1.0 0.2 dried fruits (Po) 

Flax, seed, postharvest 1.0 

Goat, fat 1.0 

Goat, meat 0.05 0.05 

Page 19 of 25 
Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition: 

US – See footnote 1 Canada Mexico2 Codex3 

Goat, meat byproducts 0.05 0.05 

Gooseberry, postharvest 1.0 1.0 

Grape, postharvest 1.0 1.0 0.2 dried fruits (Po) 

Guava, postharvest 1.0 1.0 

Hog, fat 1.0 

Hog, meat 0.05 0.05 

Hog, meat byproducts 0.05 0.05 

Horse, fat 1.0 

Horse, meat 0.05 0.05 

Horse, meat byproducts 0.05 0.05 

Loganberry, postharvest 1.0 1.0 

Mango, postharvest 1.0 1.0 

Milk, fat (reflecting negligible 

residues in milk) 

0.05 0.05 

Muskmelon, postharvest 1.0 1.0 

Oat, grain, postharvest 1.0 0.3 cereal grains (Po) 

Orange, postharvest 1.0 1.0 0.05 citrus fruits 

Pea, dry, seed, postharvest 1.0 1.0 peas 0.1 Pulses (Po); 

1 pea hay or pea 

fodder (dry) 

Peach, postharvest 1.0 1.0 

Peanut, postharvest 1.0 1.0 0.5 (Po) 

Pear, postharvest 1.0 1.0 

Pineapple, postharvest 1.0 1.0 

Plum, prune, fresh, postharvest 1.0 1.0 

Potato, postharvest 0.05 0.05 root and tuber 

vegetables (*) 

Raspberry, postharvest 1.0 1.0 

Rice, grain, postharvest 3.0 3.0 raw cereals 0.3 cereal grains (Po) 

Rye, grain, postharvest 3.0 3.0 raw cereals 0.3 cereal grains (Po) 

Sheep, fat 1.0 

Sheep, meat 0.05 0.05 

Sheep, meat byproducts 0.05 0.05 

Sorghum, grain, grain, 

postharvest 

1.0 3.0 raw cereals 0.3 cereal grains (Po) 

Sweet potato, postharvest 0.05 0.05 root and tuber 

vegetables (*) 

Tomato, postharvest 1.0 1.0 0.05 (*) 

Walnut, postharvest 1.0 1.0 

Wheat, grain, postharvest 3.0 3.0 raw cereals 0.3 cereal grains (Po) 

MRLs with NO US equivalent

Fruiting vegetables, cucurbits 0.05 (*) 

Huckleberries 1.0 

Peppers 0.05 (*) 

Page 20 of 25 
Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition: 

US – See footnote 1 Canada Mexico2 Codex3 

Peppers chili, dried 0.5 

Pulses 0.1 Po 

Completed: M. Negussie; 07/25/2011 

1

 Tolerances for residues of the insecticide pyrethrins ((1S)-2-methyl-4-oxo-3-(2Z)-2,4-pentadienylcyclopenten-1-yl 

(1R,3R)-2,2-dimethyl-3-(2-methyl-1-propenyl)cyclopropanecarboxylate (pyrethrin 1), (1S)-2-methyl-4-oxo-3-(2Z)-

2,4-pentadienyl-2-cyclopenten-1-yl (1R,3R)-3-[(1E)-3-methoxy-2-methyl-3-oxo-1-propenyl]-2,2-

dimethylcyclopropane-carboxylate (pyrethrin 2), (1S)-3-(2Z)-2-butenyl-2-methyl-4-oxo-2-cyclopenten-1-yl 

(1R,3R)-2,2-dimethyl-3-(2-methyl-1-propenyl)cyclopropanecarboxylate (cinerin 1), (1S)-3-(2Z)-2-butenyl-2-

methyl-4-oxo-2-cyclopenten-1-yl (1R,3R)-3-[(1E)-3-methoxy-2-methyl-3-oxo-1-propenyl]-2,2-

dimethylcyclopropanecarboxylate (cinerin 2), (1S)-2-methyl-4-oxo-3-(2Z)-2-pentenyl-2-cyclopenten-1-yl (1R, 3R)-

2,2-dimethyl-3-(2-methyl-1-propenyl)cyclopropanecarboxylate (jasmolin 1), and (1S)-2-methyl-4-oxo-3-(2Z)-

pentenyl-2-cyclopenten-1-yl (1R,3R)-3-[(1E)-3-methoxy-2-methyl-3-oxo-1-propenyl]-2,2-

dimethylcyclopropanecarboxylate (jasmolin 2)), the insecticidally active principles of Chrysanthemum 

cinerariaefolium, which are measured as cumulative residues of pyrethrin 1, cinerin 1, and jasmolin 1 are not to 

exceed the following 

2 Mexico adopts US tolerances and/or Codex MRLs for its export purposes. 

3 * = absent at the limit of quantitation; Po = postharvest treatment, such as treatment of stored grains. PoP = 

processed postharvest treated commodity, such as processing of treated stored wheat. (fat) = to be measured on the 

fat portion of the sample. MRLs indicated as proposed have not been finalized by the CCPR and the CAC. 

In addition, the following tolerances are established for pyrethrins: 

(2) A tolerance of 1.0 ppm is established for residues of the insecticide pyrethrins in or on milled fractions derived 

from grain, cereal when present as a result of its use in cereal grain mills and in storage areas for milled cereal grain 

products. 

(3) A tolerance of 1.0 ppm is established for residues of the insecticide pyrethrins in or on all food items in food 

handling establishments where food and food products are held, processed, prepared and/or served. Food must be 

removed or covered prior to use. 

(4) Where tolerances are established on both the raw agricultural commodities and processed foods made therefrom, the total residues of pyrethrins in or on the processed food shall not be greater than that permitted by the larger 

of the two tolerances. 

 

Page 21 of 25 
Appendix C: Required Study Rationale 

Guideline Number: 870.7800

Study Title: Immunotoxicity

Rationale for Requiring the Data

This is a new data requirement under 40 CFR Part 158 as a part of the data requirements for 

registration of a pesticide (food and non-food uses). 

The Immunotoxicity Test Guideline (OPPTS 870.7800) prescribes functional immunotoxicity 

testing and is designed to evaluate the potential of a repeated chemical exposure to produce 

adverse effects (i.e., suppression) on the immune system. Immunosuppression is a deficit in the 

ability of the immune system to respond to a challenge of bacterial or viral infections such as 

tuberculosis (TB), Severe Acquired Respiratory Syndrome (SARS), or neoplasia. Because the 

immune system is highly complex, studies not specifically conducted to assess immunotoxic 

endpoints are inadequate to characterize a pesticide’s potential immunotoxicity. While data from 

hematology, lymphoid organ weights, and histopathology in routine chronic or subchronic 

toxicity studies may offer useful information on potential immunotoxic effects, these endpoints 

alone are insufficient to predict immunotoxicity. 

Practical Utility of the Data

How will the data be used?

Immunotoxicity studies provide critical scientific information needed to characterize potential 

hazard to the human population on the immune system from pesticide exposure. Since 

epidemiologic data on the effects of chemical exposures on immune parameters are limited and 

are inadequate to characterize a pesticide’s potential immunotoxicity in humans, animal studies 

are used as the most sensitive endpoint for risk assessment. These animal studies can be used to 

select endpoints and doses for use in risk assessment of all exposure scenarios and are considered 

a primary data source for reliable reference dose calculation. For example, animal studies have 

demonstrated that immunotoxicity in rodents is one of the more sensitive manifestations of 

TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) among developmental, reproductive, and 

endocrinologic toxicities. Additionally, the EPA has established an oral reference dose (RfD) for 

tributyltin oxide (TBTO) based on observed immunotoxicity in animal studies (IRIS, 1997). 

How could the data impact the Agency's future decision-making?

If the immunotoxicity study shows that pyrethrins pose either a greater or a diminished risk than 

that identified in the RED, the risk assessments for pyrethrins may need to be revised to reflect 

the magnitude of potential risk derived from the new data. 

 

If the Agency does not have these data, a 10X database uncertainty factor may be applied for 

conducting a risk assessment from the available studies. 

 

Page 22 of 25 
Appendix D: Required Crop Field Trial Data 

EPA has previously required many crop field trial studies to support the continued registration of 

pyrethrins. A summary of the field trials needed is provided in Table D-1 below. Additional 

detail is available in the memo “Pyrethrins. Response to Comments on Residue Data 

Requirements”, C. Olinger (D366246, 10/27/09). 

Table D-1. Summary of Field Trials Needed to Support the Registration Review of Pyrethrins 

Commodity – Number of Field 

Trials Typically Required 

Number of Field Trials 

Required for Pyrethrins 

Number 

Submitted 

Number of Field Trials 

Still Needed 

CG1: Vegetable, root and tuber, group 1 

No further field trials are required for root and tuber vegetables 

CG2: Vegetable, leaves of root and tuber, group 2 

Radish Tops 0 1 0 

Turnip Tops - 5 4 0 4 

Sugar or Garden Beet Tops - 9 6 2 4 

CG3: Vegetable, bulb, group 3-07 

Green Onion – 3 3 0 3 

Bulb Onion - 6 3 0 3 

CG4: Vegetable, leafy, except brassica, group 4 

Head Lettuce – 6 4 2 2 

Leaf Lettuce – 6 5 5 0 

Celery – 6 4 2 2 

Spinach - 6 5 2 3 

CG5: Vegetable, brassica, leafy, group 5 

Broccoli - 6 4 3 1 

Cabbage – 6 5 3 2 

Mustard Greens - 5 4 2 2 

CG6: Vegetable, legume, group 6 

Succulent Bean – 12 6 2 4 

Dried Bean – 9 5 2 3 

Succulent Pea – 9 5 2 3 

Dried Pea – 5 2 2 0 

Soybean - 15 8 0 8 

CG7: Vegetable, foliage of legume, group 7 

Bean – 3 2 2 0 

Field Pea - 3 3 4 0 

Soybean - 15 8 0 8 

CG8: Vegetable, fruiting, group 8-10 

No further field trials are required for fruiting vegetables. 

CG9: Vegetable, cucurbit, group 9 

No further field trials are required for cucurbit vegetables. 

CG10: Fruit, citrus, group 10-10 

No further field trials are required for citrus fruits. 

CG11: Fruit, pome, group 11-10 

Apples – 12 9 0 9 

Pears - 6 4 0 4 

CG12: Fruit, stone, group 12-11 

Sweet or Tart Cherry – 6 4 0 4 

Peach - 9 6 3 3 

Plum - 6 4 0 4 

CG13: Fruit, berry and small fruit, group 13-07 

Blackberry or raspberry – 3 2 1 1 

Blueberry - 6 5 5 0 

Page 23 of 25 
Table D-1. Summary of Field Trials Needed to Support the Registration Review of Pyrethrins 

Commodity – Number of Field 

Trials Typically Required 

Number of Field Trials 

Required for Pyrethrins 

Number Number of Field Trials 

Submitted Still Needed 

Grape – 9 7 1 6 

Kiwifruit – 3 2 0 2 

Strawberry - 6 4 2 2 

CG14: Nut, tree, group 14-11 

Almond – 5 3 0 3 

Pecan – 5 2 0 2 

CG15: Grain, cereal, group 15 

Fresh sweet corn – 9 5 0 5 

Dried field corn – 15 8 0 8 

Rice - 12 6 0 6 

Sorghum – 9 4 0 4 

Wheat - 15 8 0 8 

CG16: Grain, cereal, forage, fodder and straw, group 16 

Corn – 15 8 0 8 

Wheat – 15 8 0 8 

Other Cereal Grain - 12 6 0 6 

CG17: Grass, forage, fodder and hay, group 17 

Bermuda grass – 4 3 0 3 

Bluegrass – 4 3 0 3 

Bromegrass or Fescue - 4 3 0 3 

CG18: Animal feed, nongrass, group 18 

Alfalfa – 9 6 6 

Clover - 9 6 6 

CG19: Herbs and spices group 19 

Basil (fresh and dried) - 3 2 0 2 

Chive – 3 2 0 2 

Dill Seed or Celery Seed – 3 2 1 A 1 

Black Pepper – 3 2 0 2 

Other Commodities 

Cotton Forage - 9 6 0 6 

CG20: Oilseed group 20 

Rapeseed (canola varieties only) - 

9 6 0 6 

Sunflower – 9 6 0 6 

Cotton, undelinted seed - 9 6 0 6 

Cotton gin-byproducts - 9 6 0 6 

CG21: Fungi, edible, group 21 

White Button Mushroom - 2 2 0 2 

Oyster Mushroom/Shitake - 1 1 0 1 

Miscellaneous Commodities 

Asparagus – 8 6 0 6 

Atemoya - 3 3 0 3 

Avocado – 5 5 0 5 

Banana – 5 5 0 5 

Coffee – 5 3 0 3 

Guava – 3 A 3 0 3 

Peanut – 12 6 0 6 

Pineapple - 8 5 0 5 

Sugarcane - 8 5 0 5 

Tea - 3 2 0 2 

Tobacco - 3 2 0 2 

Page 24 of 25 
Page 25 of 25 

A - Although the guidance specifies only two trials (with analysis of four samples from each trial), three trials will 

be required, since the guava trials will support the use on other commodities. 

Additional notes: 

• Since the time of the RED, the berry sub-group has been modified to include 

cranberries. If the registrant conducts the field trials as described below for berry group 

13-07, field trials on cranberries will not be needed. 

• In the DCI, trials on barley, rye, and oat grain were required. If the registrant completes 

the trials for the cereal grain representative commodities as described in the table below 

(crop group 15), then the trials on these grains will not be needed. 

• Field trials on cherimoya are no longer needed; data from atemoya may be translated to 

cherimoya. 

• Field trials on pomegranate are no longer needed.