Bergeson & Campbell, P.C. serves small, medium, and large pesticide product registrants and other stakeholders in the agricultural and biocidal sectors, in virtually every aspect of pesticide law, policy, science, and regulation.

By Lisa M. Campbell, Timothy D. Backstrom, James V. Aidala, and Lisa R. Burchi

On July 18, 2019, the U.S. Environmental Protection Agency (EPA) issued a pre-publication version of a Federal Register notice announcing a final order denying the Pesticide Action Network North America’s (PANNA) and the Natural Resources Defense Council’s (NRDC) 2007 Petition requesting that EPA revoke all tolerances and cancel all registrations for chlorpyrifos (Order).  This Order constitutes final Agency action denying all of the Petitioners’ objections to EPA’s previous refusal to revoke the tolerances for chlorpyrifos.  This Order also constitutes final administrative action concerning all parts of the 2007 Petition that were not previously addressed by EPA.  Given the previous extensive chlorpyrifos litigation, this latest action by EPA will likely lead to further litigation challenging EPA’s decision to allow continued use of chlorpyrifos under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and the Federal Food, Drug, and Cosmetic Act (FFDCA).

Background

The FIFRA registrations and related tolerances for chlorpyrifos have a complicated regulatory and legal history, as discussed in previous blogs available here.

EPA’s new Order denies objections made by PANNA and NRDC under the FFDCA to EPA’s March 29, 2017, order denying the request by PANNA and NRDC that EPA revoke all tolerances for chlorpyrifos and cancel all chlorpyrifos product registrations.  In the Order, EPA begins by summarizing its prior responses to the 2007 Petition, in which EPA denied each of ten claims raised in support of the Petitioners’ request that EPA revoke all chlorpyrifos tolerances and cancel all chlorpyrifos registrations.  The ten claims are:

  1. EPA has ignored genetic evidence of vulnerable populations.
  2. EPA has delayed a decision regarding endocrine disrupting effects.
  3. EPA has ignored data regarding cancer risks.
  4. EPA’s 2006 cumulative risk assessment (CRA) for the organophosphates misrepresented risks and failed to apply the Food Quality Protection Act (FQPA) 10X safety factor.
  5. EPA over-relied on registrant data.
  6. EPA has failed to address properly the exporting hazard in foreign countries from chlorpyrifos.
  7. EPA has failed to incorporate quantitatively data demonstrating long-lasting effects from early life exposure to chlorpyrifos in children.
  8. EPA has disregarded data demonstrating that there is no evidence of a safe level of exposure during pre-birth and early life stages.
  9. EPA has failed to cite or incorporate quantitatively studies and clinical reports suggesting potential adverse effects below 10 percent cholinesterase inhibition.
  10. EPA has failed to incorporate inhalation routes of exposure.

EPA’s Order next focuses on the June 2017 objections to the March 29, 2017, Denial Order that were filed by several public interest groups and states.  The three main objections, and EPA’s response, are as follows:

  • Claims Regarding the Legal Standard for Reviewing Petitions to Revoke:  Objectors assert that EPA’s Denial Order applied the wrong legal standard.  Objectors assert that neither “scientific uncertainty” nor the October 2022 deadline for registration review under FIFRA Section 3(g), nor the widespread agricultural use of chlorpyrifos, provide a basis for denying petitions to revoke. Objectors claim that EPA has unlawfully left chlorpyrifos tolerances in place without making the safety finding required by the FFDCA.
  • EPA Response:  In its Order, EPA denies the objections related to Petitioners’ claims regarding neurodevelopmental toxicity, stating that the objections and the underlying Petition are not supported by valid, complete, and reliable evidence sufficient to meet the Petitioners’ burden under the FFDCA, as set forth in EPA’s implementing regulations.  Specifically, EPA states that Objectors have not met their regulatory burden to provide “reasonable grounds” for revocation, including an assertion of facts to justify the modification or revocation of the tolerance (40 C.F.R. § 180.32(b)) or the initial evidentiary burden for persons seeking revocation to come forward with sufficient evidence to show that pesticide tolerances to be modified or revoked are not safe.  After summarizing its review of available epidemiologic data, including feedback from the 2012 and 2016 FIFRA Scientific Advisory Panel (SAP) meetings, EPA states that “the epidemiologic studies are central to the Petitioner’s claims regarding neurodevelopmental effects, yet the Petitioners and Objectors rely only on summaries in publications to present their case. Petitioners have not presented the raw data from the epidemiology studies for consideration of their claims.” EPA “concludes that the information yet presented by Petitioners is not sufficiently valid, complete, and reliable to support abandoning the use of AChE inhibition as the critical effect for regulatory purposes under the FFDCA section 408” and also that Petitioners have “failed to meet their initial burden of providing sufficiently valid, complete, and reliable evidence that neurodevelopmental effects may be occurring at levels below EPA’s current regulatory standard and no information submitted with the objections addresses this shortcoming of the Petition.”
  • Objections Asserting that EPA Has Found Chlorpyrifos to Be Unsafe: Objectors assert that EPA has previously found that chlorpyrifos tolerances are unsafe and has not disavowed those findings. Specifically, they claim that EPA has found that chlorpyrifos results in unsafe drinking water exposures and results in adverse neurodevelopmental effects to children and that EPA must therefore revoke the tolerances.
  • EPA Response:  EPA denies making any regulatory findings that chlorpyrifos tolerances are not safe, stating that its statements in its 2015 proposed tolerance revocation was not a final action.  EPA states: “Proposed rules are just that -- proposals; they do not bind federal agencies. Indeed, EPA made clear it was issuing the proposal because of the court order, without having resolved many of the issues critical to EPA’s FFDCA determination and without having fully considered comments previously submitted to the Agency.”  Regarding those objections related to drinking water, EPA states that since the Petition did not identify drinking water exposure as a basis for seeking tolerance revocation, the Objectors cannot now raise that concern as a basis for challenging EPA’s denial of the Petition. EPA also states: “The mere fact that EPA is considering the potential impact of chlorpyrifos exposures in drinking water in the Agency’s FIFRA section 3(g) registration review does not somehow provide Petitioners and Objectors with a vehicle for introducing that topic in the objections process on the Petition denial.”  EPA instead will continue its FIFRA Section 3(g) registration review and complete its evaluation of drinking water exposures to chlorpyrifos, and address these issues in its upcoming registration review decision.
  • Objections Asserting that the Denial Order Failed to Respond to Significant Concerns Raised in Comments:  Objectors argue that EPA’s Denial Order committed a procedural error by failing to address significant concerns raised in the comments on EPA’s 2014 risk assessment and 2015 proposed revocation that EPA’s assessment fails to protect children. In particular, the Objectors focus on concerns raised in comments asserting that (1) EPA’s use of 10 percemt cholinesterase as a regulatory standard is not protective for effects to children’s developing brains; (2) EPA has not properly accounted for effects from inhalation of chlorpyrifos from spray drift and volatilization; and (3) EPA inappropriately used the Corteva physiologically based pharmacokinetic (PBPK) model to reduce inter- and intra-species safety factors because the model is ethically and scientifically deficient.
  • EPA Response:  EPA denies the objections claiming procedural error, stating it “has no obligation to respond to rulemaking comments in denying the Petition or responding to objections, both of which are adjudicatory actions that are not part of the rulemaking process.  EPA also restated its prior response to the Petition that the “objections fail to meet burden of presenting evidence sufficiently valid, complete and reliable to demonstrate that chlorpyrifos results in neurodevelopmental effects that render its tolerances not safe.”  EPA further “believes it is lawful and appropriate for it to consider federally enforceable chlorpyrifos product labeling restrictions in assessing the extent of bystander risk from spray drift under both the FFDCA and FIFRA.”

Commentary

This latest EPA assessment appears to be more finely crafted than the earlier March 2017 response to the tolerance revocation Petition.  EPA explains that it does not consider the epidemiology studies cited by the Petitioners to be persuasive sufficiently to change EPA’s fundamental approach to assessing chlorpyrifos risks.  EPA notes that its current risk assessment utilizes the default 10X safety factor for infants and children specified by the FQPA, so any argument that it has not utilized this safety factor is moot.  At the same time, EPA maintains that the epidemiology studies do not justify changing EPA’s point of departure for risk assessment, which remains the threshold for 10 percent acetylcholinesterase (AChE) inhibition.  EPA states that there are significant problems with using the epidemiology studies for risk assessment, including lack of access to the underlying data, the absence of any known mechanism for neurodevelopmental effects below the threshold for AChE inhibition, and a lack of scientific consensus on a method for choosing an alternate point of departure based on the epidemiology studies.  This interpretation of the epidemiology studies for chlorpyrifos will remain controversial and these studies will continue to be cited by those who seek to eliminate chlorpyrifos use.

EPA has also taken a position that the burden is on the Petitioners to support a petition to revoke tolerances with reliable data.  What is less clear is “how much” evidence EPA considers sufficient to meet the threshold for tolerance revocation.  Meanwhile, EPA will defer its assessment of possible neurodevelopmental effects of chlorpyrifos below the threshold for AChE inhibition pending completion of the registration review for chlorpyrifos.  The deadline for EPA to complete registration review is October 1, 2022, although EPA states that it intends to expedite this process and to issue a proposed registration review decision by October 2020.

EPA also has included in its decision an intriguing discussion of some new animal studies for chlorpyrifos that purport to show low-level neurodevelopmental effects from chlorpyrifos.  The California Department of Pesticide Regulation relied substantially on these new studies when it designated chlorpyrifos as a Toxic Air Contaminant.  If these new chlorpyrifos studies are deemed credible, they could supplant efforts to use the chlorpyrifos epidemiology data in risk assessments and allow EPA to establish a new point of departure for chlorpyrifos that is not based on AChE inhibition.  Rather than disregarding these new data, which were not submitted in support of the tolerance revocation Petition, EPA says affirmatively that it intends to review them in the pending registration review.


 

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.