By Lara A. Hall, MS, RQAP-GLP and Lauren M. Graham, Ph.D.
On September 13, 2017, the U.S. Environmental Protection Agency (EPA) issued three supporting documents for the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) Scientific Advisory Panel (SAP) meeting regarding the “Continuing Development of Alternative High-Throughput Screens to Determine Endocrine Disruption, Focusing on Androgen Receptor, Steroidogenesis, and Thyroid Pathways.” This FIFRA SAP meeting will be held on November 28-30, 2017, from 9:00 a.m. - 5:00 p.m. (EST) at the EPA Conference Center, Lobby Level, One Potomac Yard (South Bldg.), 2777 S. Crystal Dr., Arlington, VA 22202.
The supporting documents include:
Written comments will be accepted on or before October 16, 2017. Comments may be submitted online via Docket ID EPA-HQ-OPP-2017-0214-0001, mail, or hand delivery.
Updated details regarding other comment periods for the FIFRA SAP are provided below:
A listing of ad hoc panel members, including their biographical sketches, was posted online on August 22, 2017. The public comment period for the proposed panel members closed on September 7, 2017.
The original Federal Register notice announcing the meeting was published on June 6, 2017.
This important meeting, and materials issued in connection with it, will have potentially significant consequences for registrants. Bergeson & Campbell, P.C. (B&C®) will continue to monitor the situation closely and provide additional updates as they become available. More information on EPA’s Endocrine Disruptor Screening Program (EDSP) as well as the FIFRA SAP are available on our blog under key terms EDSP and FIFRA SAP.
By Lara A. Hall
On August 3, 2017, the U.S. Environmental Protection Agency (EPA) published a Federal Register notice announcing revised comment period dates for the Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (FIFRA SAP) meeting regarding the “Continuing Development of Alternative High-Throughput Screens to Determine Endocrine Disruption, Focusing on Androgen Receptor, Steroidogenesis, and Thyroid Pathways.” This SAP meeting will be held on November 28-30, 2017, from 9:00 a.m.-5:00 p.m. (EST) at the EPA Conference Center, Lobby Level, One Potomac Yard (South Bldg.), 2777 S. Crystal Dr., Arlington, VA 22202. Updated details regarding commenting periods are provided below:
- Supporting documents for the FIFRA SAP meeting will be posted online on or before September 1, 2017. Written comments will be accepted on or before October 16, 2017.
The original Federal Register notice announcing the meeting was published on June 6, 2017.
This important meeting, and materials issued in connection with it, will have potentially significant consequences for registrants and should be monitored closely.
By Lisa M. Campbell and James V. Aidala
On March 29, 2017, U.S. Environment Protection Agency (EPA) Administrator Pruitt signed an order denying the September 2007 petition of the Pesticide Action Network North America (PANNA) and the Natural Resources Defense Council (NRDC) requesting that EPA revoke all tolerances and cancel all registrations for the pesticide chlorpyrifos. This is the latest EPA action in a long and contentious battle concerning chlorpyrifos tolerances and registrations, and is likely not the end of this story.
EPA’s decision denying the petition addresses each of the petition’s ten claims and the history of EPA’s review and responses to those claims. Much attention will be paid to the order’s discussion of three of the claims, which the order states all relate to the same issue: “whether the potential exists for chlorpyrifos to cause neurodevelopmental effects in children at exposure levels below EPA’s existing regulatory standard (10% cholinesterase inhibition).” The order states that because “Congress has provided that EPA must complete registration review by October 1, 2022,” and because EPA has “concluded that it will not complete the human health portion of the registration review or any associated tolerance revocation of chlorpyrifos without first attempting to come to a clearer scientific resolution” on the issues concerning potential neurodevelopmental effects in children, EPA is denying the claims, given the Ninth Circuit Court of Appeals’ August 12, 2016, order that “made clear” that further extensions to the March 31, 2017, deadline for responding to the petition would not be granted. EPA states that the “science addressing neurodevelopmental effects remains unresolved,” and “further evaluation of the science during the remaining time for completion of registration review is warranted to achieve greater certainty as to whether the potential exists for adverse neurodevelopmental effects to occur from current human exposures to chlorpyrifos.”
The order will become effective as soon as it is published in the Federal Register. More information on the prior proceedings concerning this matter is available on our blog under key phrase chlorpyrifos.
This decision by EPA under the Trump Administration to deny the petition is not surprising, given the rhetoric of reducing regulatory burdens and the need to stop regulatory “overreach” by agencies like EPA which has been accused of making politically driven decisions. EPA's press release captures this, quoting Administrator Pruitt stating (in part): "By reversing the previous Administration’s steps to ban one of the most widely used pesticides in the world, we are returning to using sound science in decision-making -- rather than predetermined results.”
EPA has, however, “kicked the can down the road” to some extent on the key science issue -- whether EPA appropriately evaluated epidemiology studies which reported that exposures to the pesticide had adverse neurological impacts on infants and children -- an issue that affects not only chlorpyrifos, but the other organophosphates (OP) that EPA has concluded are subject to a Food Quality Protection Act (FQPA) 10X factor based on these studies. (See EPA’s September 15, 2015, Literature Review on Neurodevelopment Effects & FQPA Safety Factor Determination for the Organophosphate Pesticides.)
The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) Scientific Advisory Panel (SAP) members who reviewed EPA’s approach, based on these studies with regard to chlorpyrifos, generally had concerns with its proposed approach. When EPA nonetheless issued its renewed call for revocation of the tolerances in November 2016, eight days after the Presidential election, it was seen by some as partly (if not fully) driven by a “political” calculus which ignored the lack of support of the FIFRA SAP.
The November 2016 proposal was based on more than the epidemiology studies which have proven controversial. At the same time, EPA’s arguments in the November notice relied on some of the earlier findings about the studies and FIFRA SAP’s review to fashion a “hybrid” approach which, not surprisingly, supported EPA’s previous conclusions.
This has led to charges of “politics over science” on all fronts, but in responding to the court deadline for a final decision by March 31, 2017, EPA has now declared it does indeed need more time to resolve the science issues, and argues that the general registration review process, with the chlorpyrifos review scheduled for 2022, gives EPA more time than what the court imposed. EPA has concluded that if a decision is needed now, the required burdens have not been met to change the current status of the pesticide. The order states:
- Following a review of comments on both the November 2015 proposal and the November 2016 notice of data availability, EPA has concluded that, despite several years of study, the science addressing neurodevelopmental effects remains unresolved and that further evaluation of the science during the remaining time for completion of registration review is warranted to achieve greater certainty as to whether the potential exists for adverse neurodevelopmental effects to occur from current human exposures to chlorpyrifos. EPA has therefore concluded that it will not complete the human health portion of the registration review or any associated tolerance revocation of chlorpyrifos without first attempting to come to a clearer scientific resolution on those issues.
EPA has determined it needs more time, however frustrating that may be, to sort out the science. As such, it is allowing chlorpyrifos use to continue, but objections to EPA’s decision are expected by the petitioners who originally pushed for the tolerance revocations. The effect on other OPs with regard to the application of the FQPA uncertainty factor is unclear, at best. The science debate will rage on, with no clear timeline or process for how the ultimate resolution of these questions will be “final.” This political and legal back-and-forth may become the new normal for the Trump Administration as it seeks to balance a more “business friendly” regulatory approach with the stringent requirements of the statutory duties of underlying authorizing legislation across all of EPA’s programs.
By Lisa M. Campbell, Timothy D. Backstrom, and Lisa R. Burchi
On August 12, 2016, a three-judge panel of the Ninth Circuit Court of Appeals issued an order denying the U.S. Environmental Protection Agency’s (EPA) request for an additional six months to decide whether to ban agricultural uses of chlorpyrifos. The court opted instead to afford EPA a three month extension, stating that “this is the final extension, and the court will not grant any further extensions."
EPA sought the six month extension on June 29, 2016, to allow time for EPA to complete two scientific analyses that may bear on EPA’s conclusions in the final rule, and to request further public comment before taking final action on a prior proposal to revoke all chlorpyrifos tolerances. The two analyses that EPA wanted to complete are: (1) a refined drinking water assessment that may allow EPA “to develop more tailored risk mitigation for some regions of the country,” and (2) an evaluation of the epidemiological data for chlorpyrifos to determine whether EPA should retain the point of departure based on acetylcholinesterase (AChE) inhibition in the proposed rule.
The court concluded that EPA’s request for a six month extension “is not justified in light of EPA’s history in this matter as well as the court’s previous extensions.” The court stated that EPA’s request was "another variation on a theme 'of partial reports, missed deadlines, and vague promises of future action' that has been repeated for the past nine years,” and that “nothing has changed that would justify EPA’s continued failure to respond to the pressing health concerns presented by chlorpyrifos."
The court ordered EPA to take final action on its proposal to revoke tolerances for chlorpyrifos by March 31, 2017. A further status report by EPA will be due in November 2016.
EPA’s updated analysis of the epidemiological data for chlorpyrifos will be a matter of considerable interest. After EPA issued a proposed rule utilizing a point of departure for chlorpyrifos based on AChE inhibition, EPA issued a blanket determination based on the epidemiological data for chlorpyrifos in which EPA decided to retain the Food Quality Protection Act (FQPA) safety factor for all organophosphate (OP) pesticides. This FQPA determination could cause EPA to conclude that the tolerances for chlorpyrifos must be revoked regardless of the outcome of the refined drinking water assessment.
EPA later proposed to use an alternative point of departure for chlorpyrifos based on biomonitoring data from one of the chlorpyrifos epidemiology studies, but the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) Scientific Advisory Panel (SAP) met on April 19-21, 2016, and recommended against this new approach. In its request for an extension, EPA stated that the FIFRA SAP might recommend a “hybrid approach” to adjusting the point of departure for AChE inhibition. The FIFRA SAP meeting minutes do not appear to include such a hybrid recommendation.
In a related development, EPA has reached an agreement with the Columbia Center for Children’s Environmental Health (CCCEH) regarding the release of raw data from one of the chlorpyrifos epidemiology studies. During the FIFRA SAP meeting, concerns were raised regarding use of the CCCEH study without access to the underlying raw data. In an April 19, 2016, letter to Dr. Linda P. Fried, Dean of the Mailman School of Public Health at Columbia University, EPA requested that CCCEH provide access to the underlying data. In her response dated May 18, 2016, Dr. Fried offered to work with EPA “to determine if we can develop one or more data sets that can be properly de-identified, consistent with our obligation to protect the privacy of our research subjects, and that will also enable EPA to conduct its own analyses in order to address its transparency goals” or, in the alternative, offered to allow EPA staff to review the original data “in a secure data enclave onsite at Columbia.” In its June 27, 2016, response, EPA stated that the offer to allow EPA staff to review the underlying data at a secure site did not resolve issues concerning the transparency of EPA’s analysis. This correspondence is available in EPA Docket ID EPA-HQ-OPP-2008-0850. While EPA maintained it is “unnecessary” for CCCEH and EPA to develop redacted data sets, EPA accepted CCCEH’s offer to develop such data sets.
EPA’s request for a six month extension was filed on June 29, 2016, two days after it accepted the offer by CCCEH to develop redacted data sets for the CCCEH epidemiology study. Moreover, the FIFRA SAP meeting minutes issued on July 20, 2016, do not appear to provide the guidance that EPA had expected concerning a potential “hybrid” approach to adjusting EPA’s proposed point of departure for AChE inhibition.
Given the lesser extension granted by the court, it is questionable whether EPA will have sufficient time to review adequately the redacted underlying data sets offered by CCCEH, or even to determine whether those redacted data sets are adequate for this review, and to make any determination based on such data before EPA issues a supplementary proposal based on the refined drinking water assessment and the updated epidemiology assessment. The court has stated that it will entertain no further extension requests, so EPA must complete its work expeditiously to allow time for comment before final action is due on March 31, 2017.
By Lisa M. Campbell and Timothy D. Backstrom
On July 20, 2016, the U.S. Environmental Protection Agency (EPA) issued a memorandum attaching minutes from the April 19-21, 2016, FIFRA Scientific Advisory Panel (SAP) meeting, Transmittal of Meeting Minutes of the April 19-21, 2016 Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) Scientific Advisory Panel (SAP or Panel) Meeting Held to Consider and Review Scientific Issues Associated with “Chlorpyrifos: Analysis of Biomonitoring Data.” This SAP was convened to advise EPA regarding the evaluation of biomonitoring chlorpyrifos data from epidemiology studies conducted by the Columbia Center for Children’s Environmental Health (CCCEH).
The minutes indicate that the SAP has significant concerns with EPA’s proposal to use the biomonitoring chlorpyrifos data from the CCCEH epidemiology studies to establish a point of departure (PoD) for chlorpyrifos risk assessment. The minutes state: “Because many uncertainties cannot be clarified, the majority of the Panel does not have confidence that the Columbia Center for Children’s Environmental Health (CCCEH) cord blood data on chlorpyrifos concentrations can accurately be used in quantitative risk assessment to determine a Point of Departure (PoD).” A major source of uncertainty cited by the FIFRA SAP is “the lack of verification and replication of the analytical chemistry results that reported very low levels of chlorpyrifos (pg/g),” because EPA had to impute a finite quantitative value to “a large fraction of cord blood samples included in the analyses presented with levels below [level of detection (LOD)].” Moreover, some SAP members “thought the quality of the CCCEH data is hard to assess when raw analytical data have not been made available, and the study has not been reproduced.”
The SAP also, however, stated that “both epidemiology and toxicology studies suggest there is evidence for adverse health outcomes associated with chlorpyrifos exposures below levels that result in 10% red blood cell (RBC) acetylcholinesterase (AChE) inhibition (i.e., toxicity at lower doses).” Nevertheless, it agreed with EPA that “applying additional safety factors to the AChE PoDs to account for a possible noncholinergic mode of action (MOA) would be problematic because of challenges in justifying any particular value for such an adjustment.”
Of note, the SAP concluded that it would be appropriate to use a “10X intra-species extrapolation factor” in any analysis based on the cord blood data. It also identified other sources of uncertainty that should be considered in such an analysis, including “the inability of single measures of chlorpyrifos concentration in blood to provide information regarding source, frequency, duration and magnitude of exposure, and how these exposures are linked to specific outcomes measured in the CCCEH study participants.” Although EPA suggested in a Status Report filed in the chlorpyrifos litigation pending in the Ninth Circuit Court of Appeals on June 29, 2016, that the FIFRA SAP might recommend a “hybrid approach” that EPA could use in lieu of a PoD based on AChE inhibition, thereby altering the prior EPA analysis for chlorpyrifos, the SAP minutes do not include a recommendation for such a hybrid methodology.
Given the concerns expressed by the SAP regarding EPA’s proposal to derive a PoD from cord blood biomonitoring data collected in the CCCEH epidemiology studies, it may be unlikely that EPA will further pursue this specific approach. It is less clear whether EPA will be inclined to propose any further adjustments to its existing risk assessment for chlorpyrifos, which utilizes a PoD based on animal AChE data, along with intra-species and inter-species uncertainty factors and an additional Food Quality Protection Act (FQPA) 10X factor. EPA’s decision to retain the special FQPA factor in its risk assessment for chlorpyrifos will remain controversial, because it is based on an assessment of the value and significance of several epidemiology studies for chlorpyrifos that many in the pesticide industry strongly dispute. The discussion in the minutes of the uncertainties resulting from the refusal of the CCCEH investigators to provide underlying raw data may provide further support for arguments by industry that EPA should not predicate risk assessments on the epidemiology studies for chlorpyrifos before obtaining and reviewing these data.
More information on the FIFRA SAP and its surrounding legal issues is available in our blog item EPA Requests Six Month Extension of Deadline for Decision on Chlorpyrifos Tolerance Revocation, and more generally on our blog with keyword chlorpyrifos.
By Lisa M. Campbell and Timothy D. Backstrom
On June 29, 2016, the U.S. Environmental Protection Agency (EPA) submitted a status report in the Ninth Circuit Court of Appeals case concerning a petition by Pesticide Action Network North America (PANNA) and the Natural Resources Defense Council (NRDC) to revoke the tolerances and cancel the registrations for chlorpyrifos. The Court of Appeals issued an order on December 10, 2015, requiring EPA to take final action concerning the PANNA and NRDC petition no later than December 30, 2016. To comply with an earlier order, EPA issued a proposed rule to revoke the tolerances for chlorpyrifos before it could complete a refined drinking water assessment or propose a new “point of departure” for chlorpyrifos based on biomonitoring data from an epidemiological study.
EPA’s status report states that it has made “significant progress” towards meeting the December 30, 2016, deadline, but “extraordinary circumstances exist that make it impracticable for the Agency to meet the Court’s deadline.” Based on these extraordinary circumstances, EPA has requested a six-month extension for final action on the petition.
EPA notes that a proposed new point of departure was presented to the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) Scientific Advisory Panel (SAP), but was not favorably received. At the same time, EPA states that the SAP “raised concerns about the approach EPA adopted in the Proposed Rule, namely that the continued use of acetylcholinesterase inhibition as the point of departure may not be sufficiently health protective.” EPA infers that the SAP may be disposed to recommend a “hybrid approach,” but the written SAP report will not be issued until the end of July, 2016.
EPA states that it had planned to seek public comment on its refined drinking water assessment and new point of departure for chlorpyrifos immediately after the SAP meeting. EPA now believes that it would be best to obtain the final SAP report before deciding how to establish a point of departure. Accordingly, EPA proposes to seek comment on its refined drinking water analysis and analysis of the epidemiological data by early Fall 2016, and to take final action on the PANNA and NRDC petition by June 30, 2017.
EPA expects that the refined drinking water assessment for chlorpyrifos will allow “tailored risk mitigation” that could eliminate one basis for the proposed revocation of chlorpyrifos tolerances. In contrast, EPA’s concerns about the potential neurodevelopmental effects of chlorpyrifos may not be as readily addressed by risk mitigation. If EPA decides either to retain the Food Quality Protection Act (FQPA) 10X safety factor for chlorpyrifos based on purported neurodevelopmental effects observed in epidemiological studies, or to adopt some “hybrid” risk assessment methodology for neurodevelopmental effects in response to the SAP recommendations, debate on the merits of doing so will likely be strong. The status report does not appear to suggest that EPA is currently considering revisiting its general views on the chlorpyrifos epidemiological data; if EPA is not doing so, considerable continued debate on this issue is also likely.
By Lisa M. Campbell and Timothy D. Backstrom
On March 8, 2016, the U.S. Environmental Protection Agency (EPA) published a notice in the Federal Register stating that the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) Scientific Advisory Panel (SAP) will hold a three-day meeting scheduled for April 19-21, 2016, from 9:00 a.m. to 5:00 p.m. (EDT) to consider and review Chlorpyrifos: Analysis of Biomonitoring Data. The meeting will be held at EPA’s Conference Center, Lobby Level, One Potomac Yard (South Bldg.), 2777 S. Crystal Drive, Arlington, Virginia 22202. The meeting will be webcast. More information will be posted online.
The notice states that written comments are encouraged through April 5, 2016, and that requests for oral comments are encouraged to be submitted by April 12, 2016, but that both may be submitted until the date of the meeting. Nominations of candidates to serve as ad hoc members of FIFRA SAP for the meeting are requested on or before March 23, 2016.
In this meeting, EPA states that it will solicit comment from FIFRA SAP on the evaluation of biomonitoring data using the physiologically-based pharmacokinetic (PBPK) model, proposed points of departure and extrapolation/uncertainty factors, and examples of a proposed approach to use the PBPK model to simulate internal doses of chlorpyrifos from current exposure patterns from drinking water, food, and worker exposure. The FIFRA SAP has been reviewing the human health effects of chlorpyrifos since 2008. The notice states that “at this point in time, the Agency’s analysis of biomonitoring data from the cord blood collected as part of the Columbia University epidemiology studies has progressed to a point where peer review would be useful” and that “[s]pecifically, the Agency has done additional characterization of the pharmacokinetic profile of simulated exposures from oral and dermal exposures using the PBPK model.”
The notice states that in 2008 and 2012, the FIFRA SAP “cautioned EPA against using the biomonitoring data from epidemiology studies … to directly derive points of departure due to uncertainties associated with a lack of knowledge about timing of indoor chlorpyrifos applications and a single measure of exposure (cord blood).” The 2012 FIFRA SAP recommended that EPA use the PBPK model to further characterize the dose estimates in the epidemiology studies.
The notice states that EPA would have preferred to complete its analysis of the available biomonitoring prior to commencing rulemaking, but that the timing for the proposal was directed by the U.S. Court of Appeals for the Ninth Circuit, which ordered EPA to respond to an administrative petition to revoke all chlorpyrifos tolerances by October 31, 2015.
More information on the Ninth Circuit case is available in our blog item Circuit Court Grants Writ of Mandamus Requiring EPA to Act on Petition to Ban Chlorpyrifos.
EPA’s decision to utilize biomonitoring data that was collected as part of the Columbia University epidemiology studies for chlorpyrifos to derive proposed points of departure for risk assessment purposes will be highly controversial. If EPA proceeds to use biomonitoring data from epidemiological studies to derive points of departure for risk assessment purposes, the implications for all pesticide product risk assessments could be significant. Whether EPA can defensibly do so from both a scientific and legal standpoint is a subject that will likely be debated strongly. All pesticide registrants should monitor these developments closely.