Fact Sheet: Review of the Relationship between Pyrethrins, Pyrethroid Exposure and Asthma and AllergiesCurrent as of June 2009
EPA has expedited a broad review of pyrethrins and pyrethroid incidents to identify any trends in the data. To determine whether there is an association between pyrethrins and pyrethroid products and asthma and allergy effects, EPA performed a thorough review of the animal and human data. The process of evaluation and the Agency’s conclusions are discussed in A Review of the Relationship between Pyrethrins, Pyrethroid Exposure and Asthma and Allergies (28 pp, 398k, About PDF) (US EPA, September 2009 corrected version).
This most recent review was prompted by a journal article titled ‘Safe’ Pesticides Now First in Poisonings, published by the Center for Public Integrity. The article focuses on human incidents and exposure to pyrethroid and pyrethrins pesticide products. It raises issues related to increases in numbers of incidents related to pyrethrins and pyrethroids, as well the safety of these products for individuals with asthma or allergies.On this page you will find:
- Allergies and Asthma
- Pyrethrins and Pyrethroids
- Pyrethrins Reregistration Stewardship Program
- Weight of Evidence Approach
- Animal Data
- Human Incident Data
- Human Study Data
- Weight of Evidence Conclusion
- Regulatory Conclusion
Allergies and Asthma
- An allergy is an immunologically mediated adverse reaction to a chemical resulting from previous sensitization to that chemical or to a structurally similar one.
- Asthma is a chronic inflammatory disease of the airways characterized by reversible airway constriction, usually upon inhalation of a provoking agent.
- Allergic reactions can be manifest in various ways, such as an asthmatic response or a skin reaction.
- Many symptoms that indicate asthma and allergies also indicate normal immune responses to an irritating substance.
Pyrethrins and Pyrethroids
- Crude pyrethrum, made from the chrysanthemum flower, has insecticidal properties and is a known allergen. No pyrethrum end-use products are currently registered with the Agency.
- Refined pyrethrum is called pyrethrins. Synthetic pyrethroids were developed to mimic the structure of pyrethrins and to increase photostability and enhance insecticidal activity.
- Pyrethrins and pyrethroids are not expected to elicit allergic-type reactions due to the reported removal of the allergic component in pyrethrum.
More information on pyrethrins and pyrethroids.
Pyrethrins Reregistration Stewardship Program
EPA completed the Reregistration Eligibility Decision (RED) for pyrethrins in 2006. During reregistration the Agency considered the potential association between pyrethrins products and allergy/asthma effects. As a condition of the Agency’s reregistration decision, EPA required the Pyrethrins Joint Venture (PJV) to:
- Institute a product stewardship program that involved a prospective, in-depth follow-up of reported pyrethrins incident cases in order to clarify the issue of a possible correlation between pyrethrins product use and adverse health incidents;
- Implement outreach to physicians and Poison Control Centers to provide them with better guidance and diagnostic standards.
The PJV program will be tracked by the Agency. An annual report submitted to the Agency will be required for at least 5 years.
Weight of Evidence Approach
In the current review, EPA used a weight of evidence approach to determine whether an association exists between pyrethrins/pyrethroid exposure and asthma and allergies. The current review included data from both animals and humans. The Agency considered animal data regarding:
- Mode of action
- Target organ of toxicity
- Acute inhalation and dermal irritation
The Agency also considered human data including incident data from several sources and human epidemiology studies.
In the weight of evidence analysis, EPA considered consistency, reproducibility, temporal and dose concordance, and biological plausibility of the effects reported in each data set and across all data sets. Comparisons of health effects profiles were also conducted between pyrethrins/pyrethroid products and other insecticides when possible to determine whether exposure to this class of pesticides elicits a heightened or unique respiratory/dermal response compared to other insecticides.
The animal data do not indicate that exposure to pyrethrins or pyrethroid products is associated with the development or exacerbation of asthma. Data indicate that pyrethrins/pyrethroids have low acute toxicity via oral, dermal and inhalation routes of exposure and are not skin sensitizers.
Human Incident Data
The pyrethrins/pyrethroid incident data do not consistently show an effects profile that would indicate respiratory effects to be significantly heightened or biologically different from other insecticides. If this relationship were strong, a clear and consistent pattern of effects reported across multiple human incident databases, with higher percentages of respiratory illnesses and dermal responses would be expected.
EPA considered incident data from the following databases:
- OPP’s Incident Data System (IDS)
- The American Association of Poison Control Centers (PCC)
- Food and Drug Administration’s Adverse Event Reporting System (AERS)
- National Pesticide Information Center (NPIC)
From this analysis, EPA has drawn the following information:
- Potentially supporting evidence:
- NPIC data showed that pyrethroid and pyrethrins incidents are almost twice as likely to include the keywords allergy or asthma in the record as other insecticide classes. However, the overall percentage of records with these keywords is fairly low.
- Potentially non-supporting evidence:
- PCC data showed that effects possibly indicative of asthma or allergies did not overshadow other types of effects, and that the pyrethrins/pyrethroids effects profiles were similar to other insecticide classes.
- FDA data also did not support an association between pyrethrins/pyrethroid pediculicide product exposures and allergic or asthmatic responses.
- From the limited information given in IDS reports, no apparent link between the pyrethrins/pyrethroid products and the effects reported could be hypothesized.
Human Study Data
Available human epidemiological data do not consistently show results/outcomes that indicate pyrethrins or pyrethroids cause allergic and/or asthmatic responses, nor do they provide robust evidence that pyrethrins/pyrethroids trigger an allergic and/or asthmatic response.
Overall, the existing data did not support a positive relationship between pyrethrins/pyrethroid products and asthma/allergy effects.
- A population level study (Karpati et al., 2004), showed that spraying a particular pyrethroid [active ingredients: sumithrin (10%) and PBO (10%)] for West Nile Virus control in New York City was not followed by population-level increases in visits to public hospital emergency departments – a negative finding in regards to whether pyrethroid exposure is associated with asthma.
- The Agricultural Health Study (AHS) did not report a clear association between respiratory symptoms (wheezing) and exposure to permethrin (follow-up investigation is ongoing).
Note that the human studies EPA considered do not constitute "research involving intentional exposure of a human subject" under EPA's Rule for the Protection of Human Subjects.
Weight of Evidence Conclusion
Unlike previous reviews, the current assessment utilized a weight-of-evidence approach, integrating both animal and human data, to determine whether a clear association exists between pyrethrins/pyrethroid exposure and asthma and allergies. This decision is predicated on the premise that an integrative assessment is more informative than what any single dataset or study could provide, and that fundamental biological mechanisms of disease outcome are concordant across species. Based on the current analyses, the Agency concluded there is no clear and consistent pattern of effects reported to indicate conclusively whether there is an association between pyrethrins/pyrethroid exposure and asthma and allergies.
The Agency is not requiring additional warnings or label statements specific to asthmatics on pyrethroids and pyrethrins end-use products, nor is the Agency requiring additional data from pyrethroid registrants at this time. However, as discussed above, as a condition of reregistration the Agency required the PJV to institute a product stewardship program that involved a prospective in-depth follow-up of reported pyrethrins incident cases to clarify the issue of a possible correlation between pyrethrins pesticide product use and adverse health incidents.
The Agency will review the pyrethrins incident data as it is submitted. If the Agency identifies discrepancies or trends in the data that differ from the incident data considered in this review, the Agency will consider requiring additional or similar data from the pyrethroid registrants.