By Lisa M. Campbell and Timothy D. Backstrom
On September 9, 2019, the U.S. Environmental Protection Agency (EPA) Office of Pesticide Programs (OPP) published a notice in the Federal Register announcing the availability of, and an opportunity for comment on, a document describing an “interim process” that OPP’s Environmental Fate and Ecological Effects Division is currently using to evaluate potential synergistic effects of mixtures of pesticide active ingredients on non-target organisms. As part of a lawsuit challenging the 2012 decision by EPA to register Enlist Duo Herbicide (a combination of 2,4-D and glyphosate), OPP scientists learned that patent applications for some registered pesticide products included claims that particular combinations of active ingredients provide “synergistic” control of target species. Although EPA was not at that time considering potential synergies in assessing the risk for ecological effects on non-target organisms, based on the patent application claims regarding synergy for Enlist Duo, EPA decided to request that the reviewing court vacate its registration decision and remand the application for Enlist Duo for further study of these effects and any measures that might be needed to mitigate the risk to non-target organisms. This decision sparked much controversy, and many in industry were concerned that patent application claims were not being correctly interpreted by EPA for the category of pesticide products at issue.
The new document released by EPA for review and comments is entitled: “Process for Receiving and Evaluating Data Supporting Assertions of Greater Than Additive (GTA) Effects in Mixtures of Pesticide Active Ingredients and Associated Guidance for Registrants.” EPA states that it “has generally been applying this interim process since 2016.” The process described in the document has five steps: (1) registration applicants must search for any granted patents that include synergy (GTA) claims for combinations of pesticides; (2) applicants must review the patent claims and supporting data for relevance to ecological risk assessment; (3) applicants must report to EPA all effects testing data from the relevant patents; (4) applicants must do a statistical analysis (using a method prescribed by EPA) to determine whether any observations of GTA effects are statistically significant; and (5) EPA will review all submitted information to decide whether it should be utilized in ecological risk assessment.
In the Federal Register notice, OPP lists five specific areas pertaining to the interim risk assessment process described in the document on which it is requesting comment:
- Are there technical aspects of the interim process that warrant change? If so, what changes are recommended?
- What aspects of the process could be applied to the evaluation of open literature sources of GTA effects pesticide interactions?
- Should EPA consider standardizing a more detailed search and reporting approach, and how should EPA do that?
- Should EPA continue the evaluation process as described in this document? If so, what performance metrics (e.g., number of evaluations) should EPA consider before deciding the utility of this approach?
- What applicant burden is associated with the activities described in this memorandum, including compiling, analyzing, and submitting the information? Specifically, does an estimate of 80-240 hours of burden per applicant cover the respondent burden associated with the interim process?
When the National Research Council (NRC) evaluated the importance of toxicological interactions between pesticide active ingredients in 2013, the NRC concluded that such interactions are rare, but that EPA should nonetheless consider such interactions when the best available scientific evidence supports such an evaluation. In the current Federal Register notice, EPA makes it clear that it is uncertain concerning the utility for risk assessment of the information used by manufacturers to support synergistic effects claims in pesticide patents. According to EPA, 24 applicants for new registrations have submitted patent data to date, but only three of these submissions contained information that indicated a need for further testing and no submission ultimately led to any adjustment of the ecological risk assessment. At this juncture, EPA will continue collecting patent data that may be pertinent to GTA effects, but when it has sufficient experience upon to base a general policy it may either continue or improve this process or discontinue it after explaining why.
When EPA requested that the reviewing court vacate and remand the registration EPA had granted for Enlist Duo, the parties seeking judicial review located data in the patent applications that EPA had not previously seen or reviewed and that EPA believed could possibly be pertinent to potential adverse effects on non-target plants. EPA concluded that it should revisit the decision based on the additional data. Although EPA decided to request vacatur and remand, the applicant Dow AgroSciences had arguably followed all of the procedures then in place, because FIFRA Section 3(c)(5) allows EPA to waive data requirements pertaining to efficacy, and EPA typically registers pesticide product that are not intended to protect public health without any independent evaluation of efficacy data. Nevertheless, in general EPA may choose to evaluate pesticidal efficacy data; such circumstances in the past often involved cases where EPA was required to consider whether pesticide benefits are sufficient to outweigh identified risks. In the Enlist case, EPA determined that it should do so where potential synergy in pesticidal efficacy is pertinent to evaluating ecological effects on non-target species.
What EPA must decide now is how often efficacy data that has been deemed adequate by the Patent and Trademark Office to support a patent for a new pesticide mixture will have any material significance in the context of ecological risk assessment. Before EPA makes a determination whether or not patent data has sufficient pertinence to continue requiring routine collection and evaluation of such data, EPA has decided it is prudent to afford all stakeholders an opportunity to comment on whether EPA has been asking the right questions.
All comments on the draft document must be submitted no later than October 24, 2019.
By Jason E. Johnston
On September 4, 2019, the U.S. Environmental Protection Agency’s (EPA) Office of Pesticide Programs’ Environmental Fate and Effects Division (EFED) announced that the next Environmental Modeling Public Meeting (EMPM) will be held on October 16, 2019. The EMPM is a semi-annual public forum for EPA, pesticide registrants, and other stakeholders to discuss current issues related to modeling pesticide fate, transport, and exposure for risk assessments in a regulatory context.
In a press release to the public, EPA indicates that the topics covered at the October meeting will include sources of usage data (relating to the actual application of pesticides, in terms of the quantity applied or units treated); spatial applications of usage data; model parameterization; extrapolation of usage data to fill in gaps; temporal variability of usage; and updates on ongoing topics. Presentations concerning the incorporation of pesticide usage data into environmental exposure and ecological risk assessments will also be included.
Registration is required. Requests to participate in the meeting must be received on or before September 23, 2019, as noted in the Federal Register notice.
By Lisa M. Campbell, Timothy D. Backstrom, and James V. Aidala
On August 2, 2019, the U.S. Environmental Protection Agency (EPA) Office of Pesticide Programs (OPP) announced that it has decided to reduce the Food Quality Protection Act (FQPA) safety factor for infants and children for pyrethroids from its current value of 3X to a new value of 1X. This decision is based on a July 1, 2019, OPP report entitled “USEPA Office of Pesticide Programs’ Re-evaluation of the FQPA Safety Factor for Pyrethroids: Updated Literature and CAPHRA Program Data Review.” Risk assessments incorporating the new lower FQPA safety factor for pyrethroids will be utilized in developing proposed registration review decisions for these compounds, and EPA has stated it will be taking public comment on the OPP report reducing the FQPA safety factor for pyrethroids after EPA publishes a notice of availability for the proposed registration review decisions.
Pyrethroids are a group of insecticides that includes natural pyrethrins (found in chrysanthemums) and more than 30 synthetic compounds with similar structure and activity. EPA has determined that it is appropriate to establish one FQPA safety factor for all pyrethroid active ingredients because these compounds all have the same mode of action and similar patterns of toxicity. Pyrethroid insecticides are widely used in and around residential structures, on pets, in treated clothing, for mosquito control, and in various agricultural applications. EPA indicates that although pyrethroids have relatively low mammalian toxicity, EPA believes that the principal concern for human risk assessment is a potential to cause acute neurotoxic effects.
The FQPA safety factor is intended to account for “potential pre- and post-natal toxicity and completeness of data with respect to exposure and toxicity to infants and children.” The FQPA safety factor is set by statute at a default value of 10X, but EPA may select a lower value for this safety factor if EPA determines based on “reliable data” that such a lower value will be safe for infants and children. This determination necessarily depends on EPA’s assessment of the quality of the data that address the susceptibility to adverse effects of the pesticide of infants and children. Based on current EPA guidance, OPP evaluates the need for the default FQPA safety factor of 10X in two components: a safety factor of about 3X assigned to pharmacodynamic (PD) differences and a safety factor of about 3X assigned to pharmacokinetic (PK) differences. PD differences refer to the sequence of events at the molecular or cellular level leading to a toxic response to a substance, while PK differences refer to absorption, distribution, metabolism, and excretion of the substance.
EPA previously evaluated the adequacy of the database concerning risks to infants and children posed by pyrethroid active ingredients in 2011. At that time, EPA decided that there were sufficient data concerning the mechanism for potential neurotoxic effects of pyrethroids to allow EPA to reduce the factor for PD differences to 1X, but EPA retained the 3X factor for PK differences because EPA believed that the available pharmacokinetic data for pyrethroids was not sufficient for EPA to conclude that infants and children would not confront a greater risk of neurotoxic outcomes. After EPA made the 2011 determinations, the Council for the Advancement of Pyrethroid Human Risk Assessment (CAPHRA) conducted a variety of additional research to address whether children are more sensitive to the neurotoxic effects of pyrethroid exposure, and this research assessed both PD and PK differences. CAPHRA submitted a peer-reviewed physiologically based pharmacokinetic (PbPk) model for pyrethroids to EPA in 2018. After reviewing the new CAPHRA data and the current public literature for pyrethroids, EPA has now concluded that the factor for PD differences should be maintained at 1X, but the factor for PK differences should be reduced from 3X to 1X. Collectively, these determinations mean that EPA has concluded that there are reliable data to support a determination that infants and children are not more susceptible to the neurotoxic effects of pyrethroids than adults, so there is no need to retain either the default FQPA safety factor of 10X or the previous FQPA safety factor used for pyrethroids of 3X.
The adoption by EPA of a new FQPA safety factor of 1X for all pyrethroid active ingredients will likely facilitate retention of existing use patterns and use directions for a large number of pyrethroid insecticides that are commonly used in and around human residences and workplaces.
From a larger perspective, the process by which EPA evaluated and selected a proposed FQPA safety factor for pyrethroids may be seen as typical for most pesticides or classes of pesticides. The selection of a FQPA safety factor for a particular pesticide usually is based on review of available animal data, including PD and PK data, to determine whether there is any basis for concluding that infants and children may be more susceptible to adverse effects of that pesticide than adults. Where EPA decides that the animal data addressing this question are insufficient, affected registrants and other proponents of registration can consult with EPA concerning studies that will address the uncertainties. Depending on the outcome of such studies, EPA may be able to conclude that there is a scientific basis for a partial or complete reduction of the default FQPA safety factor.
Compared to this typical evaluation process, the recent decision by EPA to retain the default FQPA safety factor for all organophosphate (OP) active ingredients, which was based on EPA’s interpretation of neurodevelopmental effects reported at low exposure levels (below the threshold for acetylcholinesterase inhibition) in epidemiology studies for chlorpyrifos, may be seen as an aberration. EPA’s decision to rely on epidemiology studies that may be susceptible to methodological biases, and the decision to utilize epidemiology studies for chlorpyrifos to set the FQPA safety factors for all OP pesticides, have both been controversial.
EPA’s recent decision to retain the current tolerances and registrations for chlorpyrifos was based in significant part on EPA’s interpretation of a PbPk model for chlorpyrifos previously submitted by DowAgro (now Corteva), which mitigated to some degree EPA’s retention of the default FQPA safety factor for chlorpyrifos. Corteva may submit further data addressing PD and PK differences for chlorpyrifos, and EPA has also stated that it intends to review some new animal studies for chlopyrifos, which purport to show neurodevelopmental effects at low exposure levels. Perhaps these data will allow EPA to establish a point of departure (POD) for chlorpyrifos risk assessment without any need for a further excursion into the unfamiliar risk assessment territory represented by EPA’s use of epidemiology data for chlorpyrifos.
By Lisa M. Campbell and Lisa R. Burchi
On May 31, 2019, Health Canada’s Pest Management Regulatory Agency (PMRA) issued its Proposed Re-evaluation Decision PRVD2019-05, Chlorpyrifos and Its Associated End-use Products: Updated Environmental Risk Assessment (Updated Environmental Risk Assessment). PMRA states that this re-evaluation “considers data and information from pesticide manufacturers, published scientific reports, and other regulatory agencies” and that “Health Canada applies internationally accepted risk assessment methods as well as current risk management approaches and policies.”
PMRA is proposing the cancellation of most uses of chlorpyrifos, including almost all agricultural uses, due to PMRA’s belief that they pose unacceptable risks to the environment. The proposal would allow a small number of uses to continue if certain label changes are made. More specifically, PMRA states that its evaluation of available scientific information “has not found acceptable risks to beneficial arthropods, birds, mammals and all aquatic biota in the environment for most current chlorpyrifos uses” but “[g]reenhouse ornamental, outdoor ornamentals (container stock only) for control of Japanese beetle larvae, indoor and outdoor structural, adult and larval mosquito uses of chlorpyrifos have been shown to be acceptable from the environmental perspective.” The label changes that PMRA states would be required for these uses to continue include the following: (1) standard environmental hazard statements to inform users of the potential toxic effects to non-target species; and (2) standard environmental advisory statements for prevention of contamination of aquatic systems and to reduce volatilization.
There is a 90-day public consultation period on the proposal, which began on May 31, 2019, during which the public may submit written comments and additional information to PMRA. PMRA states that the public may submit additional information that could be used to refine risk assessments and that the final re-evaluation decision will take into consideration the comments and information received during the comment period, which could result in revised risk mitigation measures. The re-evaluation decision document will include the final re-evaluation decision, the reasons for it, and a summary of comments received on the proposed re-evaluation decision with Health Canada’s responses.
More information on chlorpyrifos issues, including California’s recent announcement that it would be initiating cancellation proceedings of chlorpyrifos, can be found on our blog.
By Lisa M. Campbell, Lisa R. Burchi, and James V. Aidala
On May 6, 2019, the U.S. Environmental Protection Agency (EPA) announced it was releasing its Proposed Interim Registration Review Decision (PID) for glyphosate acid and its various salt forms. 84 Fed. Reg. 19782. In the PID, EPA states that it “did not identify any human health risks from exposure to any use of glyphosate” but did identify “potential risk to mammals and birds” within the application area or areas near the application area and “potential risk to terrestrial and aquatic plants from off-site spray drift, consistent with glyphosate’s use as a herbicide.” Even with these potential risks, the PID states that “EPA concludes that the benefits outweigh the potential ecological risks when glyphosate is used according to label directions” and proposes certain risk mitigation strategies, including:
- “To reduce off-site spray drift to non-target organisms, the EPA is proposing certain spray drift management measures” with specific spray drift mitigation language to be included on all glyphosate product labels for products applied by liquid spray application;
- “To preserve glyphosate as a viable tool for growers and combat weed resistance, the EPA is … proposing that herbicide resistance management language be added to all glyphosate labels” and to require measures “for the pesticide registrants to provide growers and users with detailed information and recommendations to slow the development and spread of herbicide resistant weeds”;
- Inclusion on labels of a non-target organism advisory statement to alert users of potential impact to non-target organisms; and
- “EPA is also proposing certain labeling clean-up/consistency efforts to bring all glyphosate labels up to modern standards.”
EPA states that these measures were discussed with glyphosate registrants, who do not oppose the proposed risk mitigation measures outlined in the PID.
The public can submit comments on EPA’s proposed decision at www.regulations.gov in Docket Number EPA-HQ-OPP-2009-0361. Public comments are due by July 5, 2019. In addition to the PID, EPA is also posting to the glyphosate docket EPA’s response to comments on glyphosate’s usage and benefits (dated April 18, 2019), EPA’s response to comments on the human health risk assessment (dated April 23, 2018), and EPA’s response to comments on the preliminary ecological risk assessment (dated November 21, 2018).
This PID was issued shortly after the Agency for Toxic Substances and Disease Registry’s announcement on April 8, 2019, of the opening of a docket on the draft toxicological profile for glyphosate. 84 Fed. Reg. 13922. ATSDR seeks comments and additional information or reports on studies about the health effects of glyphosate for review and potential inclusion in the profile. Comments are due by July 8, 2019.
EPA’s PID and related documents, along with ATSDR’s draft profile and the peer review which will follow, can be expected to become part of the larger debate about the potential risks of glyphosate. In 2017, EPA evaluated the carcinogenic risk of glyphosate, and released its draft human health and ecological risk assessments. See our December 19, 2017, blog item "EPA Releases Draft Human Health and Ecological Risk Assessments for Glyphosate for Public Comment" for more information.
EPA’s PID is interesting not only for the conclusions EPA reached following its review of data submitted by registrants in response to a data call-in (DCI) and following the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) Scientific Advisory Panel’s (SAP) meeting to consider and review scientific issues related to EPA’s evaluation of the carcinogenic potential of glyphosate, but for the issues that remain to be addressed. Notably, EPA states that it has not considered the petition filed on September 27, 2018, to reduce glyphosate’s tolerance because the petition was filed after the comment period for the human health and ecological risk assessments closed. Instead, EPA plans to post the petition in the glyphosate docket and address the petition concurrently with the development of the Interim Registration Review Decision.
In addition, EPA has not in the PID or related documents addressed issues regarding its Endangered Species Act (ESA) assessment or its Endocrine Disruptor Screening Program (EDSP) activities. EPA states it intends to complete an assessment of risk to ESA-listed species prior to completing its final registration review decision for glyphosate, and that it also will make an EDSP determination under Federal Food, Drug, and Cosmetic Act (FFDCA) Section 408(p) before completing its registration review. EPA also notes that it continues to evaluate risks to pollinators, and that if it determines “that additional pollinator exposure and effects data are necessary to help make a final registration review decision for glyphosate, then the EPA will issue a DCI to obtain these data.” Although there are significant areas that remain to be resolved, EPA issued the PID “so that it can (1) move forward with aspects of the registration review case that are complete and (2) implement interim risk mitigation.”
More information on glyphosate issues is available on our blog.
By Lisa M. Campbell and Timothy D. Backstrom
On August 9, 2018, the majority of a three-judge panel of the U.S. Court of Appeals for the Ninth Circuit (Ninth Circuit) issued an opinion in the latest chlorpyrifos case (League of United Latin American Citizens (LULAC) v. Wheeler, No. 17-71636) granting the petition for review of a 2017 order by the U.S. Environmental Protection Agency (EPA) that denied an administrative petition to revoke the tolerances for chlorpyrifos; vacating the 2017 order; and remanding the matter back to EPA with explicit directions to EPA to “revoke all tolerances and cancel all registrations for chlorpyrifos within 60 days.” A separate dissent stated that the court should have dismissed the case for lack of jurisdiction. Please see our blog item “EPA Denies Petition to Ban Chlorpyrifos” for more information on EPA’s denial of the petition in 2017.
EPA argued in its brief that the court lacks jurisdiction to review the 2017 order denying the petition to revoke the tolerances for chlorpyrifos because Section 408(g)(2)(C) of the Federal Food, Drug, and Cosmetic Act (FFDCA) requires EPA to rule on administrative objections to its denial of the petition to revoke the tolerances for chlorpyrifos before judicial review is available under FFDCA Section 408(h)(1).The majority opinion rejected this argument, stating that FFDCA Section 408(h)(1) “does not ‘clearly state’ that obtaining a section (g)(2)(C) order in response to administrative objections is a jurisdictional requirement.” Rather than a jurisdictional limitation, the majority construed the objections process in FFDCA as a non-jurisdictional “claims-processing rule.”In contrast, the dissenting judge agreed with EPA’s argument that the court lacks jurisdiction to review this matter until after EPA responds to the objections to the 2017 order.
After concluding that the objections process is not jurisdictional in character, the majority next considered whether the petitioners should nonetheless be required to exhaust their administrative remedies by waiting until EPA responds to their objections before obtaining judicial review.Although FFDCA Section 408(g)(2)(C) requires EPA to rule on the objections “as soon as practicable,” EPA had taken no action for 13 months after the objections were filed.The majority concluded that the exhaustion requirement should be waived “in light of the strong individual interests against requiring exhaustion and weak institutional interests in favor of it.”
EPA did not specifically address the substantive merits of the 2017 order in its brief, and the majority found that EPA has consequently “forfeited any merits-based argument.”The 2017 order was issued in the context of an administrative record in which EPA has repeatedly determined that the FFDCA standard for maintenance of chlorpyrifos tolerances (“a reasonable certainty that no harm will result from aggregate exposure to the pesticide”) could not be met because of the risk of neurodevelopmental effects. The standard for registration under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) incorporates this same FFDCA standard. Although the 2017 order stated that “the science addressing neurodevelopmental effects is unresolved,” it did nothing to alter these prior EPA determinations. The majority noted that EPA’s assertion that “significant uncertainty” remains regarding the health effects of chlorpyrifos being directly at odds with the “reasonably certainty” standard and “therefore mandates revoking the tolerance under [FFDCA Section 408(b)(2)(A)(i)].” The majority concluded that the possibility that future evidence may contradict EPA’s current determinations cannot justify continued inaction, and that the failure of EPA to proceed with the revocation of the tolerances and the cancellation of the registrations for chlorpyrifos “has now placed the agency in direct contravention of the FFDCA and FIFRA.”
The court’s direct instruction requiring EPA to proceed promptly with revocation of all tolerances and cancellations of all registrations for chlorpyrifos represents an unusually aggressive judicial intervention in the administrative process.Nevertheless, this outcome must be viewed in the context of an eleven year history beginning with an administrative petition that requested the same relief, followed by a writ of mandamus in 2015 from the same court requiring EPA to make a prompt decision on the petition.Although substantial controversy remains concerning the correct interpretation of epidemiology studies with chlorpyrifos, it appears that the court believes that EPA has not taken any action that would support a change in EPA’s prior conclusion that these studies constitute evidence of potential neurodevelopmental effects in children at chlorpyrifos exposure levels below the threshold for acetylcholinesterase (AChE) inhibition. Had EPA’s 2017 denial of the administrative petition been accompanied by an amended risk assessment for chlorpyrifos which articulated a changed conclusion, the court may have been less likely to substitute its judgment for that of EPA.The court seemed to find that because the scientific assessments in the current administrative record could not support the “reasonable certainty” standard in the FFDCA, the conclusion it reached on the merits was unavoidable.
Please see our blog item “Oral Argument Held in Case Challenging EPA’s Denial of Petition to Revoke Chlorpyrifos Tolerances” for information on the oral argument that took place on July 9, 2018, and the briefing in this case. Further information on the case proceedings is available on our blog under key word chlorpyrifos.
By Lisa M. Campbell and Timothy D. Backstrom
In July 2018, the California Environmental Protection Agency’s Department of Pesticide Regulation (DPR), Human Health Assessment (HHA) Branch, issued its final toxic air contaminant (TAC) evaluation of chlorpyrifos. This final TAC evaluation updates the December 2017 draft evaluation of chlorpyrifos as a TAC for the Scientific Review Panel (SRP) which updated the August 2017 draft and was reviewed by the SRP on TACs, and incorporates certain changes based on SRP recommendations. As part of their review of the December 2017 draft, the SRP recommended “additional and detailed review of developmental neurotoxicity studies, in particular recent in vivo animal studies as well as a more in depth analysis of human effects of chlorpyrifos” and “that DPR reevaluate the critical endpoints, the associated [(uncertainty factors (UF)], and the resulting [reference concentrations (RfC)] and [reference doses (RfD)] for each endpoint.”
DPR determines that a pesticide is a TAC for a non-cancer adverse effect if the projected air concentrations associated with use of the pesticide are more than one tenth of the inhalation RfC established based on animal toxicity and epidemiology data. In the draft TAC evaluation for chlorpyrifos, DPR utilized the threshold for red blood cell acetylcholinesterase (AChE) inhibition in humans and a target margin of exposure (MOE) of 100, including a factor of 10 intended to account for potential neurodevelopmental effects below the threshold for RBC AChE inhibition. In the final TAC evaluation for chlorpyrifos, DPR increased the MOE for AChE inhibition to 300, based on deficiencies in the human inhalation parameters used to model the threshold for AChE inhibition.
In addition, the final TAC evaluation establishes a new No Observed Effect Level (NOEL) for neurodevelopmental effects in animal studies with chlorpyrifos reported at exposure levels well below the threshold for AChE inhibition. Based on this NOEL, DPR has derived a new inhalation RfC for neurodevelopmental effects, using a standard MOE of 100 consisting of 10X for interspecies sensitivity and 10X for intraspecies variability. This new inhalation RfC based on neurodevelopmental effects in animal studies is about one-half the revised inhalation RfC based on the threshold for AChE inhibition. Because the modeled spray drift air concentrations for chlorpyrifos are more than one tenth of this new inhalation RfC, DPR concludes “that chlorpyrifos meets the criteria to be listed as a TAC pursuant to the law of California.”
In the final TAC evaluation for chlorpyrifos, DPR concluded that there is sufficient evidence from animal studies to establish a new NOEL for neurodevelopmental effects, which is well below the level that has been shown to cause AChE inhibition in the same animals. Although the U.S. Environmental Protection Agency (EPA) has previously issued a determination that the default 10X safety factor for infants and children established by the Food Quality Protection Act (FQPA) should be retained for chlorpyrifos, this determination was based on epidemiology studies that purported to show adverse neurodevelopmental outcomes in humans at exposure levels below the threshold for AChE inhibition. The methodology used in these epidemiology studies has been harshly criticized by the pesticide industry. DPR views these epidemiology studies as providing corroboration, but the new DPR risk assessment is predicated instead on DPR’s view that animal studies with chlorpyrifos report neurodevelopmental effects below the threshold for AChE inhibition. The DPR risk assessment based on these animal studies uses a standard MOE of 100. How EPA may or may not view DPR’s conclusion is not known. In light of the August 9, 2018, decision by the U.S. Court of Appeals for the Ninth Circuit (Ninth Circuit) directing EPA to proceed with revocation of all tolerances and cancellation of all registrations for chlorpyrifos, the effect of the DPR conclusion on EPA actions is not clear. Nevertheless, it is worth noting that, because the mechanism by which chlorpyrifos would cause such neurodevelopmental effects is unknown and is below the level that causes AChE inhibition, any presumption by EPA that other organophosphate (OP) pesticides may cause the same type of effects will likely be vigorously disputed by industry on scientific grounds.
Please see our blog item Ninth Circuit Directs EPA to Revoke all Tolerances and Cancel All Registrations for Chlorpyrifos for more information on the Ninth Circuit’s August 9, 2018, decision.
By Jason E. Johnston, M.S.
On May 23, 2018, the U.S. Environmental Protection Agency (EPA) held an “Environmental Modeling Public Meeting” (EMPM). As stated in the April 12, 2018, Federal Register notice announcing the meeting, the “EMPM provides a public forum for EPA and its stakeholders to discuss current issues related to modeling pesticide fate, transport, and exposure for pesticide risk assessments in a regulatory context.” The overall theme of the EMPM was the quantitative use of surface water monitoring data.
The morning session featured a series of presentations by representatives from EPA, the U.S. Geological Survey (USGS), and the Washington State Department of Agriculture concerning the development of a framework to use surface water monitoring data quantitatively in pesticide risk assessments. A major focus of the presentations was the exploration and evaluation of the capabilities of the USGS recently-developed model SEAWAVE-QEX to improve the robustness of surface water monitoring datasets so that they might be used in pesticide risk assessments. Further public presentations on the evaluation and development of the framework are scheduled at the American Chemical Society meeting to be held on August 19-23, 2018, in Boston, Massachusetts. There are plans to hold a Scientific Advisory Panel meeting on the framework in 2019, but no exact date has been set.
The afternoon session consisted of presentations by representatives of the registrant community. Topics addressed included developments in the use of surface water monitoring data in quantitative risk assessment, a statistical analysis of non-targeted monitoring data at the watershed scale, the creation of a curated database of water and sediment monitoring data for synthetic pyrethroids, the use of high-resolution spatial and temporal monitoring data to parameterize watershed scale drift exposure predictions, and an evaluation of model predictability using monitoring data and refined pesticide use at the watershed level.
Presentations from the May 23, 2018, EMPM will soon be posted to Docket No. EPA-HQ-OPP-2009-0879, accessible at www.regulations.gov.
Registrants should monitor these activities, as this effort at EPA represents a potential shift away from the current reliance exclusively on estimated water concentrations in quantitative human health and ecological risk assessments.
By Lisa M. Campbell, James V. Aidala, and Lisa R. Burchi
Beginning on January 23, 2018, the European Commission (EC) opened a consultation period on the European Food Safety Authority (EFSA) risk assessment process (scientific advice). The EC states it is seeking feedback on its process both as a “follow-up to the commitments made by the Commission in reply to the European Citizens’ Initiative on glyphosate,” and in response to “citizens [that] have put into question the risk assessment based on studies provided by the industry and this in particular where the industry seeks an authorisation, e.g. for pesticides, GMOs etc.”
The General Food Law Regulation established EFSA, an independent scientific agency, to provide the risk assessment component of its risk analysis principle; the other two components are risk management and risk communication. EFSA provides its scientific opinions “which form the basis for the measures taken by the [European Union (EU)] in the food chain.” The EC states the General Food Law Regulation “is the cornerstone of the EU regulatory framework covering the entire food chain: ‘from farm to fork.’” The EC is requesting feedback to help it “look into how [the EC] can improve the current system and to address citizens’ expectations about independence and transparency of the EU risk assessment system.” The EC is specifically requesting views and experiences on the following:
- The transparency and independence of the EU risk assessment system with respect to the underlying industry studies and information on which EFSA's risk assessment/scientific advice is based;
- Risk communication; and
- The governance of EFSA, in particular the involvement of the EU Member States (MS) in the EU risk assessment system.
To contribute, interested parties must fill out the online questionnaire available here. All stakeholders and EU as well as non-EU citizens are welcome to contribute to this consultation. The consultation period will close on March 20, 2018.
This Consultation is of significant interest to stakeholders, particularly in balancing the potential need for increased transparency with the need to protect confidential business information, trade secret information, and proprietary expensive data investments. Decisions made by EFSA also could have a global impact on data protection, as any decisions made by EFSA to increase transparency could affect whether certain data can continue to be protected under other regulatory programs.
Outside of the transparency issues that are receiving much attention of late, it is important to note generally that views about risk assessment policies across governments tend to be driven by underlying political disagreements, with support or criticism somewhat predictable depending on how the resultant decisions are “for or against” the view of an interested constituency.
The transparency issue here should be considered not only on its own merits, but also within the controversy that surrounded the EU assessment approach for glyphosate, an herbicide which is widely used in production of genetically modified crops. As a stalking horse for the EU debate about biotechnology crops, the EU glyphosate assessment has, for example, become embroiled as part of the glyphosate carcinogenic classification of the International Agency for Research on Cancer (IARC). See our blog item IARC Announces Cancer Classification for Glyphosate and Other Pesticides. The IARC review concluded that glyphosate is a “probable human carcinogen,” contrary to most other assessments done by the U.S., Canada, and some EU Member States. Comments on the general EU risk assessment process can be expected to be intertwined with the perspective that any commenter has on the glyphosate assessment, even though the request is for public comment on the assessment process generally, and not only specifically about glyphosate.
More information on glyphosate is available on our blog under key word glyphosate.
By Timothy D. Backstrom, James V. Aidala, and Lisa M. Campbell
On December 18, 2017, the U.S. Environmental Protection Agency (EPA) announced it is releasing for public comment the draft human health and ecological risk assessments for glyphosate. EPA’s Draft Human Health and Ecological Risk Assessments for Glyphosate website states that the “draft risk assessments and supporting documents will be available in glyphosate’s registration review docket EPA-HQ-OPP-2009-0361 on www.regulations.gov in early 2018,” and that EPA will “open a 60-day public comment period for the draft risk assessments, evaluate the comments received, and consider any potential risk management options for this herbicide.” Many of the assessment documents, including the draft human health risk assessment, are already available on EPA’s website, but not yet posted in the docket.
The EPA announcement includes the following summary of EPA’s determinations:
- The draft human health risk assessment concludes that glyphosate is not likely to be carcinogenic to humans. The Agency’s assessment found no other meaningful risks to human health when the product is used according to the pesticide label. The Agency’s scientific findings are consistent with the conclusions of science reviews by a number of other countries as well as the 2017 National Institute of Health Agricultural Health Survey.
- EPA’s human health review evaluated dietary, residential/non-occupational, aggregate, and occupational exposures. Additionally, the Agency performed an in-depth review of the glyphosate cancer database, including data from epidemiological, animal carcinogenicity, and genotoxicity studies.
- The ecological risk assessment indicates that there is potential for effects on birds, mammals, and terrestrial and aquatic plants. EPA used the most current risk assessment methods, including an evaluation of the potential effects of glyphosate exposure on animals and plants.
EPA states the proposed interim registration review decision for glyphosate is scheduled to be published in 2019.
This latest EPA announcement is consistent with other determinations concerning glyphosate made by EPA in recent years, including statements made during the Obama Administration. EPA presented its analysis of the carcinogenic potential of glyphosate to the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) Scientific Advisory Panel (SAP) in December 2016. EPA has consistently taken the position that the human health risks from glyphosate are low, and that food and water residues of glyphosate easily satisfy the requirement that they be “safe” for human consumption.
Critics of glyphosate use often focus on the widespread adoption of glyphosate-resistant bioengineered crops. If these genetically modified organism (GMO) crops were not specifically designed for use in conjunction with glyphosate, there would likely be much less discussion about the safety of the herbicide.
Because EPA’s announcement includes a statement that “there is potential for effects on birds, mammals, and terrestrial and aquatic plants,” critics of glyphosate and the associated GMO crops will likely continue to press for restrictions based on the ecological effects of glyphosate. Moreover, there is also likely to be continued controversy concerning the human health effects of glyphosate. Notwithstanding the human health safety findings in this EPA assessment and the other assessments cited in EPA’s statement, the International Agency for Research on Cancer (IARC) has classified glyphosate as “probably” carcinogenic to humans. It is thus probable that the controversy concerning glyphosate and the associated GMO crops will continue unabated.
More information on glyphosate issues is available on our blog under key word glyphosate.