> Adverse Effects/6A2 Reports
Posted on July 15, 2021 by Lisa M. Campbell
By Lisa M. Campbell and Lisa R. Burchi
On July 12, 2021, the U.S. Environmental Protection Agency (EPA) announced in the Federal Register a notice of availability of a petition filed on April 8, 2021, by the Center for Biological Diversity (CBD) requesting that EPA cancel Elanco US Inc.’s (formerly Bayer Healthcare LLC) Product, PNR1427, more commonly known as Seresto (Petition). 86 Fed. Reg. 36546. The Petition also requests that EPA suspend the registration pending the requested cancellation. Seresto has been registered under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) since 2012 for flea and tick treatment on adult dogs and puppies and on adult cats and kittens.
Comments on the Petition are due on or before September 10, 2021, in docket EPA-HQ-OPP-2021-0409.
Under FIFRA Section 6(b), EPA may cancel a pesticide product’s registration if it appears to EPA that the pesticide, “when used in accordance with widespread and commonly recognized practice, generally causes unreasonable adverse effects on the environment.” In its Petition, CBD states that, “according to a recent aggregate incident summary report, since this product was introduced in 2012, EPA has received over 75,000 adverse incident reports, including at least 1,698 reports linking the use of this product to pet deaths and at least 700 involving human harm.” CBD states this product “contains as active ingredients the neonicotinoid imidacloprid (10%) and the pyrethroid flumethrin (4.5%).” CBD states further, “Understanding each of these ingredients, alone and in combination, is important for understanding the toxicity and risks that their use in Seresto presents to dogs, cats, humans, and exposed threatened and endangered species.” With regard to imidacloprid, CBD states in its Petition, “Neonicotinoids like imidacloprid are most well-known for the harms they cause to pollinator species, including threatened and endangered pollinators like the Poweshiek skipperling (endangered), Dakota skipper (threatened), and rusty patched bumble bee (endangered).” The Petition discusses several studies and EPA risk assessments related to both ingredients, as well as what it describes as the “synergistic effects” of the combination of imidacloprid and flumethrin. CBD argues that Seresto poses an unreasonable risk to human health, pets, and the environment and that EPA should cancel the registration pursuant to FIFRA Section 6(b).
CBD additionally argues that EPA should suspend the registration, asserting that EPA can suspend a pesticide’s registration under FIFRA Section 6(c)(1) when such action is necessary to prevent an “imminent hazard” during the time required for cancellation. The standard to be met to be considered an imminent hazard is high, as “imminent hazard” is defined under FIFRA Section 2(l) as “a situation which exists when the continued use of a pesticide during the time required for [a] cancellation proceeding would be likely to result in unreasonable adverse effects on the environment or will involve unreasonable hazard to the survival of a species declared endangered or threatened.” CBD argues that suspension is warranted in this case because, CDC asserts, both criteria for an imminent hazard are satisfied -- CDC asserts that the products at issue pose both “ongoing and imminent unreasonable adverse effects on the environment and unreasonable hazard to the survival of the endangered rusty patched bumble bee, as well as other imperiled pollinators).”
This Petition is one prong in a larger effort by certain groups to halt sales and use of Seresto. EPA’s press release statements indicate that EPA shares some concerns raised by the petitioners, at least with regard to incidents involving pets. EPA further stated in its press release that it is reviewing additional information requested by EPA from the current and former registrant regarding these incidents, and that it will use that information “along with any relevant information received during the public comment on this petition, to determine if any additional action is needed.” It will be important to monitor EPA’s review and response to this petition.
Posted on August 27, 2015 by Lisa M. Campbell
By Lara A. Hall, MS, RQAP-GLP, Jane S. Vergnes, Ph.D., DABT®, and Lisa M. Campbell
On Tuesday, August 25, 2015, in a Federal Register notice, the U.S. Environmental Protection Agency (EPA) announced the addition of three Office of Chemical Safety and Pollution Prevention (OCSPP) final test guidelines to its 890 Series, entitled “Endocrine Disruptor Screening Program Test Guidelines,” as follows:
These test guidelines are part of a series of test guidelines established by OCSPP for use in developing data on potentially adverse effects of pesticides and chemical substances on the endocrine system for submission to EPA under the Federal Food, Drug, and Cosmetic Act (FFDCA) section 408 (21 U.S.C. 346a), the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) (7 U.S.C. 136, et seq.), and the Toxic Substances Control Act (TSCA) (15 U.S.C. 2601, et seq.). These final guidelines have been revised based on public comments received following the release of draft test guidelines in January 2015, existing EPA test guidelines, and concurrent Organisation for Economic Co-operation and Development (OECD) test guidelines.
EPA worked with OECD to harmonize test guidelines for MEOGRT and LAGDA. The specific OECD Guidelines for the Testing of Chemicals, Section 2, that apply to MEOGRT and LAGDA, are available here. Substantive changes reflected in the final OCSPP MEOGRT and LAGDA test guidelines include:
1. The test will end following hatching of the second generation (F2) offspring. The option for extending the MEOGRT through reproduction by the F2 generation has been removed from the final test guideline pending additional data. This is consistent with the decision made in the draft OECD test guideline for MEOGRT. This test guideline may be updated as new information and data are considered. For example, guidance on extending the F2 generation through reproduction may be potentially useful under certain circumstances (e.g., chemicals with high bioconcentration potential or indications of trans-generational effects in other taxa).
2. The mean water temperature over the duration of the MEOGRT has been changed to 25 ± 2 °C to be consistent with the analogous OECD test guideline.
3. The LAGDA developmental stage terminology has been clarified to avoid confusion with what is meant by complete metamorphosis.
4. An effort was made to clarify and provide more explicit guidance as to what specific histopathology is appropriate based on the results of the study, e.g., the conduct of liver and kidney histopathology in the MEOGRT and LAGDA test guidelines with respect to overt toxicity.
5. The rationale for use of solvent control only, dilution water control only, or pooled controls in the statistical analyses for the MEOGRT and LAGDA was clarified.
6. The guidelines have been modified to address commenters' concerns that they be more flexible and less prescriptive. Examples have been provided as appropriate to add clarity.
The JQTT draft test guideline (OCSPP 890.2100) was revised to address comments provided by the public, the draft OECD test guideline for the avian two-generation toxicity test in the Japanese quail, as well as the existing EPA test guidelines and OECD test guidelines for avian one-generation toxicity tests.
EPA revised the terminology, procedures, endpoints measured, figures, tables, and appendices in the JQTT test guideline to clarify specific points raised by public commenters, and to address commenters' concerns that they be more flexible and less prescriptive, as follows:
1. The revised test guideline includes fewer endpoints. For example, the revisions eliminated behavioral endpoints to reduce the overall numbers of birds required for the study; eliminated endpoints that are difficult to obtain (i.e., hormone levels measured in embryo blood samples); and eliminated redundant endpoints and statistical analyses.
2. For clarity, the test terminates with measurement of the 14-day survival of the F2 generation chicks. This is the minimum length of the study necessary to evaluate and measure a chemical's effect on the first generation’s (F1) reproductive performance. If delayed reproduction is observed in F1 birds, a decision to extend the F2 generation may be made. If extended, the test should be terminated when F2 birds are approximately 6 weeks old, when 90 percent of control animals have reached sexual maturity. The decision to limit the length of the JQTT is consistent with EPA's efforts to move to extended one-generation reproduction test protocols for Tier 2 testing rather than require multigenerational studies. Extended one-generation reproduction tests are scientifically justified in many cases, reduce the use of animals in testing, and reduce costs.
Electronic access to OCSPP test methods and guidelines is available here.
The release of these final testing guidelines marks another significant step in the overall Endocrine Disruptor Screening Program (EDSP), making way for the anticipated Tier 2 testing phase with the List 1 chemicals. EPA recently released Tier 1 weight-of-evidence assessments for List 1 substances in the EDSP and registrants are now receiving the associated data evaluation records (DER) for the Tier 1 screening studies. The purpose of the Tier 1 screening was to identify potential interactions with three hormonal pathways (estrogen, androgen and thyroid) in the endocrine system. As a result of the potential interactions with one or more of these pathways observed, EPA has recommended Tier 2, multigenerational studies across various species for 18 of the 52 List 1 chemicals, including the MEOGRTS (13 chemicals) and LAGDA (5 chemicals). Test Orders for Tier 2 studies will be issued following completion of the Information Collection Request (ICR) process within the Office of Management and Budget (OMB). The public review and comment period for this ICR concludes on September 2, 2015, with a response from OMB to follow in early October 2015. In the interim, registrants are closely reviewing their respective assessments and DERs, and industry groups are assessing the approach employed by EPA in these Tier 1 assessments, including but not limited to, the statistical reanalysis of study data and conclusions drawn by EPA.