EPA issues policy on use of modern non-animal approaches for assessing endocrine disruptors

The EPA Endocrine Disruptor Screening Program (EDSP) is full of good news this week! Hopefully you saw my earlier post about acceptance of ToxCast data to satisfy the estrogen binding data requirement for certain chemicals. You may want to go read that first, if you have not done so already.

In tomorrow’s Federal Register, EPA will announce a new policy regarding “how EPA is planning to incorporate an alternative scientific approach to screen chemicals for their ability to interact with the endocrine system.”  This Federal Register announcement is to accompany the scientific support published last week by EPA in the Browne et al (2015) publication in Environmental Science & Technology. 

In essence, the information is the same … EPA has developed an approach to more rapidly screen the thousands of chemicals it needs to screen under EDSP (see the “EDSP Universe” here) in more cost-effective manner that will allow for mass prioritization of chemicals for subsequent testing that will reduce use of animals in toxicological testing.  The approach involves use of high-throughput toxicology data (generally, in vitro and in chemico/biochemical assays) generated through the ToxCast effort and integrating the relevant results into a computational “ER Model” (an in silico approach) to allow for individual chemicals to be scored for overall “bioactivity.”  The first such effort in this regard is described in detail in the Browne et al. paper.  Of over 1800 chemicals tested in the ER Model, over 1700 had “very low or no detectable ER bioactivity.” (As a complete aside, given that this entire 19-year very-slow-moving novel regulatory program was essentially founded on the notion that environmental exposure to xenobiotics was perturbing the estrogen pathway, its fabulous news that the vast majority of chemicals screened to date do not show appreciable estrogen bioactivity.)  It should be noted that the approach was vetted by the EPA’s Scientific Advisory Panel devoted to FIFRA, the federal pesticide law, in December 2014.  Based on this review and the Browne et al (2015) publication, EPA has concluded that “ER Model data are sufficient to satisfy the Tier 1 ER binding, ERTA and uterotrophic assay requirements.”  Even better, in future test orders issued under EDSP, the recipient will be allowed to cite the ER Model data as “Other Scientifically Relevant Inforamtion” (OSRI) or generate data using the 18 assays from ToxCast that were integrated into the ER Model or generate the ER binding, ERTA and uterotrophic assays per existing guidance.

Further advancements of in vitro, in chemico and in silico approaches will allow for similar efforts to be undertaken for the androgen and thyroid pathways as well.  In addition, this approach will hopefully establish proof-of-principle before wider application, such as to industrial chemicals under TSCA (which of course, is likely to undergo transformation as well in near future … see here and here for examples … but that is a different story). Expansion of this work will continue in several notable ways:

1.       EPA is still researching an androgen analogue to the ER Model (“AR Model”). When done and validated, this can be expected to fully replace the AR binding assay and Hershberger assay and partially replace the male rate pubertal and fish short-term reproduction study.

2.       Steroidogenesis and thyroid bioactivity models are also underway, which would fully replace the aromatase/steroidogenesis assays and amphibian metamorphosis assay, respectively.  They would also help partially replace the pubertal assays and the fish short-term reproductive study.

The eventual goal is to develop a set of non-animal high-throughput methods and models to fully replace all 11 Tier 1 assays.  It has been estimated that each compound tested in the full Tier 1 battery uses at least 600 animals and costs at least $500,000 overall, no including time, costs and resources that companies must devote to preparation on the regulatory submittals, review of the data prior to submission, development and submittal of OSRI, etc.  

EPA is soliciting public comments on the policy for at least 60 days from tomorrow (I can foresee the deadline getting extended for another 30 days, upon request from the regulated community and other interested parties).  Specifically, they are looking for comment on use of ToxCast/ER Model to replace the ER binding, ERTA and uterotrophic assays as well as comment on use of the screening results for the 1800 chemicals in a similar fashion.

“You’ve Come a Long Way, [EPA] Baby…”

This late 60s era slogan for cigarettes marketed specifically to women is an odd source of inspiration for a quote to celebrate EPA’s progress in non-animal testing, but there it is.  That’s what popped into my head immediately.

I’ve been following this progress fairly closely for years now and, since 2008, have dutifully served as a working member of an EPA committee devoted to 21st-century toxicology testing. This committee came about to assist EPA implement the paradigm shift underway in modern toxicology as described in the now classic 2007 report authored by the National Research Council (NRC): Toxicity Testing in the Twenty-first Century: A Vision and a Strategy.  EPA asked NRC to review the “state of the science and create a far-reaching vision for the future of toxicity testing” and the NRC laid a long-term vision that aims to transform toxicity testing through incorporation of in vitro, in chemico, and in silico tools to understand pathways of biological adversity on a molecular level. Basic discovery in this area is being organized following an “adverse outcome pathway” (AOP) framework that eventually will quantitatively link a “molecular initiating event” up through the cellular, organ and organism level response to some “adverse outcome” of regulatory concern.  (Collectively, these AOPs are being stored in a central repository through a project organized by the OECD but used internationally.)

In terms of regulatory implementation of this new way of doing business (i.e. a “bottom-up” approach to understanding pathways of disease, as opposed to a “top down” model where we study whole animals and measure apical responses), the EPA has been leading the charge with its Endocrine Disruptor Screening Program (EDSP).  This first-of-its-kind testing program was set up via legislative mandate in 1996 and has wound its way through several Presidential administrations and several hundred millions of dollars since then to establish a tiered testing program to help assess the effects of environmental exposure to chemicals that act as hormones (specifically, estrogen, androgen and thyroid hormones).  The program is very unique in that it seeks to understand endocrine “modes of action” through a battery of in vivo and in vitro tests in an initial screening battery, potentially followed by a more definitive testing strategy with whole animals to derive dose-response information needed for human health and ecological risk assessments.  However, doing so has been difficult as technology moves much quicker than government regulatory programs and the EPA has taken a “learn as we go” approach to the overall implementation of the EDSP.  Most importantly, EPA has laid out its own long-term vision for the future of EDSP and, again, this relies on greater incorporation and use of “high-throughput” approaches to the relevant in vitro and in chemico tools.

Why is this all important? Since the inception of EDSP, test order recipients (i.e. companies who have registered pesticides with the EPA that are now being assessed under EDSP) have had the option of submitting “Other Scientifically Relevant Information” (OSRI) in support of a response to the test order.  In some cases, EPA has waived the necessity to run certain tests based on the available information submitted (i.e. based on the OSRI submitted), but in the case of EDSP, not very many have been waived.  Furthermore, EPA has relied upon the more modern non-animal tools at its disposal for agency decision making.  One such example is the use of its Toxicity Forecaster (ToxCast) and in vitro testing to evaluate chemicals used as oil dispersants in the most recent oil spill in the Gulf of Mexico. Industry and animal welfare advocates have long argued that these EPA-curated non-animal data should be accepted as part of the OSRI evaluation for individual chemicals under EDSP; however, EPA initially resisted the idea of allowing use of ToxCast data in support of OSRI submissions.

So back to EPA and Virginia Slims …

In the interceding years since the first OSRI collection in 2009, there has been an explosion of research activity and publications by the EPA computational toxicology group in the Office of Research & Development.  This group has been steadfast about developing and implementing the “EDSP21” approach that the Office of Pesticide Programs will use to assess the endocrine effects of chemicals in the environment and has been fairly prolific in recent years at scientific conferences, like Society of Toxicology.

So NOW … drum roll please …

NOW … EPA is accepting ToxCast data in support of OSRI submissions for the EDSP program!!  On June 12, the journal Environmental Science & Technology released a “Just Accepted” manuscript by an interoffice group at EPA which states clearly that “EPA is accepting ToxCast ER model data for 1812 chemicals as alternatives for EDSP Tier 1 binding, ER transactivation and uterotrophic assays.”  This corroborates identical remarks made by lead author Patience Browne at a recent public meeting of the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM).

While it is unclear when the next round of OSRI submission will be, it is known it will be in conjunction with collection of the next round of data and will include both pesticides (and metabolites) and drinking water contaminants.  In some cases, there will be little available data and expert assistance may be needed to help identify and position what is available into an acceptable OSRI submission.

For now, congrats EPA … you’ve come a long way, baby.

EPA SAP to discuss integrated strategies to characterize juvenile sensitivity to pyrethroids

The Office of Pesticide Programs (OPP) at EPA has announced a meeting of the FIFRA Scientific Advisory Panel for May 19-21, 2015 to "consider and review research to evaluate the potential for juvenile sensitivity to pyrethroids."  Specifically, OPP is working on a re-evaluation of human health effects of pyrethroids and pyrethrins under registration review and, under direction of an SAP convened in July 2010, the Panel proposed a more modern approach to assessing juvenile and post-natal sensitivity as current methods (i.e. developmental neurotoxicity assays) were inadequate for this endpoint.  This more modern approach embraces the recommendations of the landmark National Academies of Sciences report on Toxicity Testing in the 21st Century by employing a integrated strategy relying on in vitro studies, targeted in vivo studies, and physiologically-based pharmacokinetic (PBPK) models.  

Specifically, the SAP will consider an industry proposal that follows this modern approach. The Council for the Advancement of Pyrethroid Human Health Risk Assessment (CAPHRA) is looking to expand its past work evaluating the "potency of pyrethroids to human sodium channels and transplantation of adult and juvenile rat synaptic membrane into oocytes" done with deltamethrin and permethrin and expand this to be more applicable across pyrethroids and pyrethrins by developing integrates testing plans and collecting targeted data sets amenable to read across and other in silico approaches for the rest of the chemical family.

A solid approach that directs resources where they need to go, saves animal life and based on M³ode of Action.

From the announcement to be published in tomorrow's Federal Register: 

"Based on feedback from the SAP and the agency, the industry research proposal was revised. Since late 2010, the Council for the Advancement of Pyrethroid Human Health Risk Assessment (CAPHRA) has worked with industry and academic scientists to develop assays and models to assess the potential for juvenile post-natal sensitivity to pyrethroids. The on-going research effort is organized around the adverse outcome pathway (AOP) for pyrethroids: Alterations with voltage-gated sodium channels (VGSC), leading to alterations in membrane excitability and firing potentials and ultimately to in vivo clinical syndromes. Specifically, the CAPHRA is evaluating the potency of pyrethroids to human sodium channels and transplantation of adult and juvenile rat synaptic membrane into oocytes. In addition, the CAPHRA is conducting targeted in vivo studies on behavioral metrics and developing PBPK models. The research, thus far, has focused on development of the overall approach using data for deltamethrin and permethrin (Type II and Type I pyrethroids, respectively). The CAPHRA research is at a point where feedback on extending this research to the other pyrethroids would be constructive. The CAPHRA proposal is to use the knowledge gained with deltamethrin and permethrin to develop more targeted data sets using read across and computational approaches (i.e., less data generation) for other pyrethroids. As such, the agency will be seeking the SAP's advice on the current state of the science with the CAPHRA research effort and proposals for next steps which include extension of data on deltamethrin and permethrin to other pyrethroids."

Case Studies in M³ODE: Glyphosate and Carcinogenicity

I'm sure many toxicologists around the world were a little puzzled by the recent carcinogenicity category assigned to glyphosate (i.e. the active ingredient in "Roundup" and found in over 750 products worldwide) by the International Association for Research on Cancer, the specialized cancer agency of the World Health Organization.  (By the way, it was "Group 2A," meaning "probably carcinogenic to humans.") 

Some of the confusion and speculation in the subsequent news stories (now over 16,000 strong) is likely rooted in past carcinogenicity reviews and what may be an incomplete consideration of the evidence.  Settling speculation on whether the latest chemical threat can actually lead to the biological outcome of concern is best done through a M³ODE ANALYSIS (i.e. Mode of Action) approach.

Past Carcinogenicity Reviews

First and foremost, the EPA has reviewed this as the primary regulator in the US.  The IRIS program in 1993 determined that glyphosate was not classifiable due to lack of animal data, but that there was no evidence it was genotoxic.  EPA is also currently performing "registration review" on glyphosate and additional details are expected this year.  [WHO, through its International Program on Chemical Safety, agreed with this conclusion in its 1994 review, and again in 2004, through the Joint Meeting of the FAO Panel of Experts on Pesticide Residues in Food and the Environment. ]

Most recently, the federal agency for risk assessment in Germany performed a comprehensive review in 2014 and concluded the following:

“In conclusion of this re-evaluation process of the active substance glyphosate by BfR the available data do not show carcinogenic or mutagenic properties of glyphosate nor that glyphosate is toxic to fertility, reproduction or embryonal/fetal development in laboratory animals. As a result of the re-assessment for the active substance BfR proposes slight amendments of the reference values. BfR believes that there is convincing evidence that the measured toxicity of some glyphosate containing herbicides is the result of the co-formulants in the plant protection products (e.g., tallowamines used as surfactants). Therefore BfR calls special attention to the co-formulants and incorporated a toxicological assessment of tallowamines in its draft report.”

— Federal Institute for Risk Assessment (BfR)

This is not an exhaustive review of the cancer reviews performed by major regulatory programs around the world. It must be noted that IARC reviews are "qualitative scientific reviews and are not meant to be formal human risk assessments" (such as the one performed most recently by Germany and quoted above) and the conclusions drawn by IARC - which shall appear on more detailed form as a Monograph at some later point in time - appeared appear draw most heavily from three cohort studies (one from the United States, one from Sweden and one from Canada) reporting increased risk of non-Hodgkin lymphoma, a group of related blood cancers.  While the Agricultural Health Study, a very large cohort of ~ 80,000 of farmers in North Carolina and Iowa studied by the National Cancer Institute, "did not show a significantly increased risk of non-Hodgkin's lymphoma," this was clearly not strong enough evidence for NCI scientist and IARC Working Group Chair, Aaron Blair.

Incomplete Consideration of the Evidence?

Again, the full Monograph will be released, but the sneak peek of the analysis provided in the Lancet over the weekend gives the impression that more recent evidence specific to glyphosate (and not part of a larger study examining groups of pesticides) was not considered:

• Private consultant Larry Kier published a review of the available human biomonitoring study data for glyphosate-based formulations (i.e. jugs of actual Roundup, including the other formulants, like surfactants) in the March 2015 Critical Reviews in Toxicology. His conclusion was these formulations "do not appear to present significant genotoxic risk under normal conditions of human or environmental exposures," which was found to be in agreement with his previous assessment of the available experimental genotoxicity data.  These papers strongly suggest a non-genotoxic mode of action, if anything.
• The most recent and comprehensive analysis of both public and private (i.e. data submitted by companies to regulatory authorities) experimental glyphosate data in rat and mouse was published by the industry Glyphosate Task Force also in the March 2015 Critical Reviews in Toxicology.  They review nine (9) rat studies and (5) mouse studies performed from 1981 through 2009, along with other data.  The publication is very thorough and worth reviewing, but beyond my attention span here.  The final conclusion is worth noting, references left in for your pleasure:
  • "The absence of a glyphosate-related mechanism for
    carcinogenesis, the huge volume of genotoxicity data studies indicating no likely mutagenic or DNA-reactive potential (Kier and Kirkland 2013), combined with the lack of epidemiological evidence for glyphosate-induced cancer (Mink et al. 2012), and the lack of carcinogenicity in multiple rodent carcinogenicity assays, are depicted in a causal inference grid in Figure 2, as put forth by Adami et al. (Adami et al. 2011). The overwhelming weight of the available evidence, demonstrating a lack of both biological plausibility and epidemiological eff ects, draws a compelling conclusion that glyphosate ’ s carcino- genic potential is extremely low or non-existent." [causal inference grid found below]
• The science & engineering consulting firm Exponent published two very comprehensive reviews of available epidemiologic data for both cancer and non-cancer health outcomes in 2012 and 2011, respectively.  Their conclusions for both were that  no "consistent pattern of positive associations indicating a causal relationship" could be found; however, they noted much uncertainty surrounding exposure measurement in general for any individual pesticide and recommended greater use of biomarkers in future epidemiologic research.
• Two scientists from IARC performed a systematic review and meta-analysis of over forty (40) studies across 30 years examining pesticide use and non-Hodgkin lymphoma published in 2014.  They found "associations between pesticides and NHL subtypes were reported; B cell lymphoma was positively associated with phenoxy herbicides and the organophosphorus [sic] herbicide glyphosate" in a "handful of papers." They concluded: "Despite compelling evidence that NHL is associated with certain chemicals, this review indicates the need for investigations of a larger variety of pesticides in more geographic areas, especially in low- and middle-income countries, which, despite producing a large portion of the world’s agriculture, were missing in the literature that were reviewed."  However, the finding specific to glyphosate is that "[t]here was a positive association between exposure to organophosphorus [sic] herbicide, glyphosate, and B cell lymphoma;" however, the 95th percentile surrounding the relative ratio for the meta-analysis was 1.1 to 3.6 -- when this statistic includes 1.0 on the low end, it is likely not a statistically significant finding.  [Ed. note: glyphosate is a "glycine phosphonate" and not an organophosphorus.] 

M³oving forward

Looking at the causal inference grid of Adami et al. (2011), both biological plausibility of glyphosate being a carcinogen is low as is the level of epidemiologic evidence, making the overall likelihood of a causal relationship between glyphosate and carcinogenicity "unlikely."

Adami HO , Berry SC , Breckenridge CB , Smith LL , Swenberg JA , Trichopoulos D , et al . (2011) . Toxicology and epidemiology: improving the science with a framework for combining toxicological and epidemiological evidence to establish causal inference . Toxicol Sci , 122 , 223 – 34 .

In the case of chemicals where there is a lack of biological data and perhaps a compelling case made by the epidemiology data, there are simple tools and tiered approaches to understanding the biological pathway through which effects might operate (i.e. mode of action, toxicity pathway, adverse outcome pathway ... however you decide to describe M³ODE).  In the specific case of glyphosate, this is probably overkill, but use of toxicogenomics approaches to screen the entire transcriptome for gene expression activity can be a "quick and dirty" approach to understanding if a chemical operates through some selective mode of action (Or many. Or none.)  There have been several such attempts in the literature as well as supporting data submitted to EPA to help understand glyphosate's potential role as an endocrine disruptor (i.e. Endocrine Disruptor Screening Program).

In any event, the critics of any chemical may not be silenced with additional studies demonstrating or refuting the biological plausibility of health effects; however, collecting data in a tiered fashion that is fit for purpose (for the regulatory need, the social need, etc.) can be done using these modern methods that only use animals as a last resort. Following the core principles of M³ode, M³argin and M³anagement can get you there.

PETA International Science Consortium RFP for in vitro method development

REQUEST FOR PROPOSALS FOR IN VITRO METHOD DEVELOPMENT
 

The PETA International Science Consortium Ltd. (PISC) is accepting proposals for funding of the development and preliminary validation of in vitro methods for hazard assessment of inhaled aerosolized multiwalled carbon nanotubes. This request builds on recommendations from a February workshop at which experts from various sectors and disciplines considered requirements for in vitro models for this purpose and made recommendations on cell types, exposure systems, endpoints, and dosimetry considerations for such systems.
 

The deadline for proposals is May 29. More information and an application form are available at http://www.piscltd.org.uk/wp-content/uploads/2015/03/PISC-RFP-FINAL_FORM-2.pdf.

EPA and FDA announce data-sharing agreement for chemicals

Taken straight from the press release. This type of data-sharing is critically important to the future of chemical risk assessment and adheres to M³'s core principles of

• MANAGEMENT: managing risks starting with using all available information (which this agreement expands); and
• MODE: A larger "chemical space" allows for more refined predictive utility of computational models.

I'm encouraged by the collaborative spirit in regulating antimicrobials moving forward.

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Data Sharing Memorandum of Understanding (MOU) between EPA and FDA

EPA and the Food and Drug Administration are pleased to announce a Memorandum of Understanding to share data on pesticides and toxic substances. This sharing of information will better inform both agencies’ assessments of the risks to the public and the environment.

FDA and EPA have complementary roles in their regulatory authority for some substances incorporated into food (including animal food and feed), animal drugs, and cosmetics. FDA is responsible for protecting and promoting the public health by ensuring, among other things, the safety of food (including animal food and feed), animal drugs, and cosmetics by enforcing the Food, Drug and Cosmetic Act and several related public health laws. EPA is responsible for managing the pesticides and toxic substances programs under the Federal Insecticide, Fungicide, and Rodenticide Act, the FD&C Act, and the Toxic Substances Control Act. The MOU establishes a process of disclosure and sharing of their respective databases that will facilitate the decisions of each agency related to food safety, veterinary medications, and cosmetics. This data sharing will provide the most up-to-date information and assist in coordinating reviews between agencies.

Sometimes a given substance may be regulated by both agencies. For example, a manufacturer of an antimicrobial food wash is required to demonstrate to FDA that its use is safe and does not adulterate food. The manufacturer may also be required to demonstrate to EPA that use of the same substance (labeled as a pesticide) will not hurt the environment.  This agreement regarding information sharing and opening channels of communication between the agencies will serve to facilitate the accomplishment of our respective missions.  The MOU is available at www.regulations.gov.  Enter the following docket number in the Search field: EPA-HQ-OPPT-2003-0004.  Read the Federal Register Notice announcing this MOU at:

https://www.federalregister.gov/articles/2015/02/27/2015-04149/access-to-confidential-business-information-by-the-food-and-drug-administration-office-of-foods-and

Frank R. Lautenberg Chemical Safety for the 21st Century Act issued in the US Senate

Yesterday, yet another bipartisan TSCA reform bill (now called Frank R. Lautenberg Chemical Safety for the 21st Century Act, S. 1009) is being sponsored by 8 Dems and 8 Republicans. Section 3A (Policies, Procedures and Guidance) to "address testing, safety assessments and determinations, and science, including policies aimed at reducing animal testing" and Section 4 "requires the Administrator to minimize the use of animals in testing through specific testing mandates, a strategic plan and research on non-animal test methods."  

Stay tuned for more insightful analysis as the way the proposed bill handles non-animal testing.

Press release available from Vitter's office -http://www.vitter.senate.gov/newsroom/press/vitter-udall-introduce-landmark-legislation-to-protect-our-families-from-toxic-chemicals

10-page overview of the bill - http://www.scribd.com/doc/258282642/Udall-Vitter-Fact-Sheet-on-Frank-R-Lautenberg-Chemical-Safety-for-the-21st-Century-Act

M³ is establishing a new direction for 2015

It took some time to establish the exact area where M³ would strive for success, but a new year and an imminent change of season has decided that path.  M³ is now a consulting company working to support the future of chemical risk assessment through the advancement of modern non-animal methods of toxicity and exposure evaluation.  

The sheer volume of chemicals in commerce with a paucity of safety information coupled with international legislative and societal pressure to reduce the use of animals in product safety testing have necessitated the adoption of modern "high-throughput" methods of assessing both the toxicity of chemicals as well as the potential exposure to the public from their use in consumer goods, pesticides, pharmaceuticals, etc.  The desired commercialization of emerging and rapidly developing technologies (such as products enabled by nanotechnology, synthetic biology and genetic modification) and introduction of new molecules and product formulations (such as biologically-sourced molecules or "discovered" computationally) threatens to severely stress existing governmental regulatory approval systems.  This could stifle product approvals and failure to act (or react) in an effective and efficient manner could undermine confidence in public trust.  

Bold leadership as well as subject matter expertise in science and regulation is needed to transform existing legislative programs, inform and advise future "21st century" law and policy and influence and educate the private and public sectors on the "21st century" approach to risk science.

As such, the "three Ms" have taken on a new meaning: Mode, Margin and Management.

• Mode (of Action): A mechanism-based approach to the risk assessment of all chemicals is already happening.  In the age of "Big Data," the shift from low-throughput data collection based on observation of phenotypic outcomes to high-throughput methods data collection relying more on in vitro, in silico,  and in chemico measurements managed through expert systems and using integrated testing approaches was inevitable.
• Margin (of Exposure): Both the ability for regulatory programs to prioritize limited resources and the capacity for the public to understand and appreciate rests on accurate measurement and communication of the frequency and duration and exposure to environmental chemicals.  Advancement of research supporting the development of high-throughput "exposure-to-activity" and Margin of Exposure estimates (for example) is critical to ensuring testing using animals is reserved for only high-risk chemicals.  
• Management: Professional and competent management of risk, using modern probabilistic approaches supported by high-throughput approaches to toxicity and exposure evaluation, will require internationally-coordinated and -supported effort, not to mention database(s) of empirical and predictive "mode-of-action" data on chemicals. Professional management of information will be needed to develop more automated approaches to using and interpreting high-throughput data via expert systems, machine learning, data mining, and structure-based modeling.  Professional management of policy and regulatory issues will be needed to organize existing information, establish evidence-based "best practices" and focus resources on information needs, not information gaps.  The Adverse Outcome Pathway concept holds tremendous promise as this new informational framework.  

In summary, the expertise and services now offered by M³ will help ensure these the future approach to toxicity and exposure evaluation (and ultimately, chemical risk assessment) is practical yet protective yet achieves the goal of reducing, refining and replacing the use of animals.  Our consultative services offer a low-cost and flexible option for clients interested in supporting the future of chemical risk assessment through the advancement of modern non-animal methods of toxicity and exposure evaluation.

EPA's Design for the Environment program calling for more info from industry

I came across a curious press release from EPA today that announced that the Design for the Environment (DfE) program is "expanding its efforts."  The method by which it is doing so is decidedly odd.  In their own words:

"The EPA Office of Chemical Safety and Pollution Prevention (OCSPP) is announcing an initiative to expand the Design for the Environment (DfE) Safer Chemical Ingredients List (SCIL) with chemicals in new and existing functional component classes.  We are inviting chemical manufacturers to submit information on their safer chemicals to EPA for review and listing on the SCIL."

This is odd as DfE normally issues guidance first. For example, EPA has issued criteria for greener solvents that one is to follow when preparing a submittal for DfE.  One complaint in the past was that the SCIL criteria are not relevant to active ingredient in pesticide formulations and the DfE response was to promise a new set of criteria for pesticide AIs, rather than follow the "General Screen" (which almost assures the AI will not pass the screen).  [And in fact, the pilot program that DfE ran for antimicrobial AIs had very limited participation ...]

This "expansion" basically tells manufacturers to work with the DfE contractors (who are NSF International and ToxServices LLC) to prepare a submittal "based on the program’s safer chemical criteria" which "EPA will use the profile and Agency criteria and expertise to make the listing decision."  So in other words, it will rely on existing guidance to make decisions on new DfE submittals and make a judgement call as to whether the submittal meets the criteria or not.

This case-by-case approach to regulation in the absence of clear and applicable guidelines is poor governance.  If DfE wants to expand functional categories of safer chemicals, it should do the appropriate regulatory guidance development first.  The current effort seems like the group is simply fishing for info on green replacements with little guidance.

USDA Forest Product Laboratory leads the charge for nanocellulose commercialization

The US Department of Agriculture Forest Products Laboratory has issued a landmark report that "details the pathway to commercializing affordable, renewable, and biodegradable cellulose nanomaterials from trees."  FPL has also created a nifty interactive infographic explaining the "Promise of Wood-Based Nanotechnology."  (FPL is perhaps better known in the DC area for its annual open house for the White House Christmas Tree.) Cellulose nanomaterials have the potential to replace uses of carbon fiber in a wide variety of applications, such as electronics, construction, food, energy, health care, automotive, aerospace, and defense.  Harvesting wood from fire-prone forests for processing into nanocellulosic materials holds great potential to improve resiliency of US forests as well. 

Obama climate gambit gets more complicated with impending SCOTUS review of "Mercury Standard"

Things just got REALLY interesting for EPA.

As if things weren't bad enough with the increasing GOP scrutiny regarding new EPA rules (for ai emissions from power plants, clarifying the waters of the US, etc.),  earlier this week it was announced that the Supreme Court will review an April 2014 decision made by the DC District Court.  In this decision, the appellate court rejected the industry challenge to the 2011 rule establishing first-ever emissions standards for oil- and coal-powered plants for mercury, arsenic and acid gases (Mercury and Air Toxics Standards).  Not surprisingly, the rule was challenged based on the assertion that all the costs were no considered during the EPA analysis of the rule.  (This has been alleged many times in recent years, including the proposed revision to the worker protection standard for agricultural workers.)

This continues the troubles and critique of the current administration's approach to climate change, where most recently a group of state Attorney Generals commented against the most recent revisions ("Clean Power Act" revisions to carbon pollution standards).  To make it a perfect trifecta, EPA most recently announced a proposal to lower the ozone standard as well.

It seems rather unlikely that the Obama climate gambit will go unchecked or unmodified by the conservative Supreme Court rule review and the yet more conservative 114th Congress; however, it has been argued that the current administration is a "winning streak" with SCOTUS.  This will be a case to watch in 2015!

Canadian provincial government releases plan to dramatically reduce neonic use by 2017

The Ontario government outlined a strategy to dramatically reduce the use of neonic seed-treatment in the Canadian province by 2017.  The action appears to be preferentially based on the WIA, released in phases earlier this year and which I described here, and the more recent EPA assessment of the benefits of neonic seed treatments for soy in the US.  The folks in Ontario have now cast their lot in with the Europeans in terms of deploying precautionary legislative approaches in the face of incomplete data.  We'll see what the results are.

As described in HazMat magazine: 

The Ontario government has announced a plan to protect bees, butterflies and other pollinating insects from the harmful effects of neonicotinoid pesticides.
In a discussion paper posted to the Ontario Environmental Bill of Rights (EBR) registry, the government outlined a strategy to reduce the use of neonic-coated seeds in the province by 80 per cent by 2017.

“Studies have confirmed that neonic pesticides are killing bees, harming a host of insects and wildlife and are accumulating in our fields and waterways,” said David Suzuki Foundation researcher and analyst Lisa Gue, in a statement. “Ontario is the first government in North America to take the tough and timely action necessary to protect pollinators and safeguard our soils, water and food.”

Neonics disrupt the central nervous systems of insects and are most often applied to seeds so the chemical becomes incorporated into the plants’ leaves, pollen, nectar, fruit and flowers. In June, an international task force of 29 independent scientists released a four-year assessment of 800 peer-reviewed studies into neonics and systemic pesticides.

Their Worldwide Integrated Assessment highlighted harmful effects of neonics on bees and serious risks to many other beneficial species, including butterflies, earthworms and birds. Close to five-million acres of corn and soy were planted in Ontario last year. Virtually all corn seed and 60 per cent of soy are treated with neonics. The U.S. Environmental Protection Agency also recently found that these seed treatments provide “little or no overall benefits to soybean production.”

“Despite the clear and present danger neonics present and the questionable benefits, Canada has been inexplicably slow to react — until now,” Gue added. “We hope other provinces and the federal government take notice of today’s announcement and move toward banning neonics in Canada.”

Health Canada is responsible for pesticide regulation in Canada. Provincial governments also have the power to regulate use and sales of pesticides within their boundaries. The proposal has been posted on the EBR for a 61-day public review and comment period, which will include public consultations in London, Toronto and Kingston.

WOTUS rule to be killed in 2015?

Last week, the (Waters of the US) WOTUS comment period closed and there was still fairly widespread opposition to it in the industry blogosphere and both business groups and Republicans remain opposed.  In fact, the House passed a bill preventing EPA from making changes to the WOTUS rule in September 2014 and, with the recent flip in the Senate, this bill looks like it stands little chance. Senator Inhofe (R-OK) has already called for EPA to withdraw its proposal.  

The now-closed docket has registered a mind-boggling 492,000+ comments from the public. To put that in perspective, here's the public response from a few other recent "big ticket" EPA dockets:

1. The Agricultural Worker Protection Standard Revisions registered 176,000+ comments. This is the first major revision to the standard in over 20 years and, similarly, there is a fair amount of opposition to the rule based on what appears to be a poorly done cost/benefit analysis.
2. The EPA decision to register the choline salt of herbicide 2,4-D on crops engineered to be resistant to 2,4-D registered 417,000+ comments.
3. EPA's "Clean Power Plan," which is arguably the most-opposed issue (by industry) currently stands at 1.25 MILLION comments and growing (docket closes on December 1).

So while folks are not as riled up regarding the WOTUS rule as they are regarding the emission standards for electricity generators, this is still a pretty major issue that is now in the hands of the GOP to resolve.  Once the all-GOP Congress handles Keystone and the Clean Power Plan, it will turn its attention to other burdensome EPA regulations... WOTUS could be high on the secondary list.

Upcoming webinar - EPA’s Worker Protection Standard for Agricultural Pesticides: Do the Benefits Outweigh the Costs?

One week left to sign up for my webinar: EPA’s Worker Protection Standard for Agricultural Pesticides: Do the Benefits Outweigh the Costs?  The EPA has proposed the first revisions to the WPS since the mid-90s.  I'll walk you through what the EPA is proposing, what it costs and it means for agricultural and commercial establishments.  In addition to learning about the WPS, I'll offer tips and advice for regulatory professionals for interacting with the US government during rulemaking.

Intended benefits of the session include:

1. Knowledge of proposed (and existing) legislation that impacts operations of agricultural companies and producers;

2. Resources for understanding federal rulemaking;

3. Resources to interact with the federal government during rulemaking; and

4. Tips and tools that companies (large and small) could use to enhance their regulatory affairs and compliance profile.

I'm doing this in conjunction with AudioSolutionz, see the sign-up page here.

Good news! The webinar is approved for 1 CM credit by the American Planning Association (APA) and you can find more info here. Earn while you learn!

What's in store for EPA from the new GOP-led Congress?

It shouldn't come as a surprise to anyone that the GOP-led Congress will probably take a hard look at some of EPA's policies in the next two years and it probably will make some changes. Perhaps some big ones.  

Where WILL it look?

I think the first place they will look is obvious.  Say it with me: climate change, climate change, climate change.  The Clean Power Plan may be first. Or perhaps something related to energy production and/or energy independence, like approval of the Keystone XL pipeline. (I'm not holding my breath for solar panel credits for everyone ....)  After last night's election, the Senate has a filibuster-proof majority on this issue (thanks in part to Democrat support on the issue... remember this creates lots of jobs in both red and blue states)

I think the Waters of the US (WOTUS) rule may be high on the list as well. There appears to be growing resistance to this reform from the ag community and the resistance is inflamed by stories like the Wyoming man being monetarily threatened by EPA for building a small pond on his property.

Where SHOULD it look?

In my mind, the GOP-led Congress has a golden legacy opportunity in front of them: meaningful industrial chemical reform (i.e. "TSCA reform").  This has gone through its requisite mutliple-year long vetting and discussion process, where now deceased Sen. Frank Lautenberg (D-NJ) led the charge for years until most recently by across-the-aisle colleague Sen David Vitter (R-LA). The pair introduced a bipartisan bill in 2013 prior to Lautenberg's passing.  The GOP could easily ride this legislation home in the next session if it was made a priority.

I still think there are EPA programs that have simply not lived up to expectations and perhaps big changes should be considered.  One of these programs is the Integrated Risk Information Program (IRIS), which I have written about before.

There may be an interest in other areas where the costs outweigh the benefits, such as the proposed revised Worker Protection Standard for agricultural employees.  A hard look at the numbers used to develop the rule reveal that the costs may in fact outweigh the benefits for the rule as proposed - a topic I will discussing online on November 19.

There has seemingly been undue amounts of influence at EPA during this administration from environmental and public health NGOs, in particular the Natural Resources Defense Council. I wouldn't be surprised at all if the GOP decided to investigate the influence of advocacy groups in the US government.

Really, it is up to the GOP how they want to work with or not work with EPA over the next two years.  It appears evident that a climate regulatory battle will commence shortly, but what POSITIVE CHANGE can the party effect along the way?

EPA and USDA to host "listening sessions" to solicit public feedback on Pollinator Health Task Force

In the November 5 Federal Register, EPA and USDA will announce two upcoming listening sessions to solicit "stakeholder input on best management practices including pesticide risk mitigation, public-private partnerships, research, education opportunities, pollinator habitat improvements, and other actions that the Task Force should consider in developing a Federal strategy to reverse pollinator losses and help restore populations to healthy levels."

EPA will host the November 12, 2014 meeting will be held at 1 Potomac Yard South, 2777 Crystal Dr., Arlington, VA, in the lobby-level Conference Center.  USDA will host the November 17, 2014 meeting will be held at 4700 River Rd., Riverdale, MD 20737.  Both sessions will be available via webcast as well.

The Task Force was set up via Presidential Memorandum on June 20, 2014.  The memo (Creating a Federal Strategy to Promote the Health of Honey Bees and Other Pollinators) set up the Pollinator Health Task Force to be co-administered by the Secretary of Agriculture and the Administrator of the EPA and includes many federal agencies as members, to include the Domestic Policy Council, Office of Science Technology and Policy and the National Science Foundation.  

The memo further directed the Task Force to develop a "National Pollinator Health Strategy" no later than 180 days after the release of the memo.  Its seems quite possible this Strategy will not be available this calendar year and seems more likely that this will be delivered to the White House in January 2015.  The Strategy shall include an action plan for pollinator research, a plan for expanding and coordinating public education and recommendations to establish private/public partnerships to "encourage the protection of pollinators and increase the quality and amount of habitat and forage for pollinators."  I would argue that this education plan must include folks on the Hill, as past letters have clearly indicated an overall lack of understanding of the technical and scientific issues.

Individual member agencies are also expected to prepare agency-specific action plans by the 180-day deadline (again, roughly December 20, 2014).  The Council on Environmental Quality and the General Services Administration actually had 90-day deadlines (these were due towards the end of September 2014) to "revise their respective guidance documents for designed landscapes and public buildings to incorporate, as appropriate, pollinator-friendly practices into site landscape performance requirements to create and maintain high quality habitats for pollinators" while USDA had a 90-day deadline to "develop best management practices for executive departments and agencies to enhance pollinator habitat on Federal lands."

EPA, in the meanwhile, has been slowly working on many regulatory aspects of pesticide use to ensure pollinator health is not damaged by label-directed uses.  These efforts include compiling a list of residue mortality values for bees, making changes to the ecological risk assessment process, directing registrants to make certain labeling changes, issuing guidance for investigating pesticide-related bee kills, and analyzing the benefits of seed treatment compounds that have been associated with adverse bee health.

Comments are being taken by the EPA Pesticide Re-evaluation Division at regulations gov, see Docket # EPA-HQ-2014-0806.

Montgomery County expands efforts to ban pesticides

Montgomery County (Maryland) Council Vice President George Leventhal is evidently about to introduce legislation to ban the use of certain pesticides on lawns.  The trigger for action is linked to potential health outcomes, specifically those pesticides "classified as carcinogenic or likely to be carcinogenic to humans by the U.S. Environmental Protection Agency."  The bill will also require the County adopt an integrated pest management (IPM) plan. IPM plans are commonly to manage pesticide use and to ensure other (non-chemical) options are exhausted.  

EPA, of course, examines carcinogenicity potential for every pesticide it registers.  The list of compounds evaluated for carcinogenicity through October 2012 has an interesting disclaimer that is worth examining:

How should the information provided in this list be used? 

Although this list is available to the public, note that the list represents only the potential carcinogenicity hazard for the chemical with no consideration of exposure information. This list is not intended to be used independent of the full risk assessment for the chemical. When EPA completes a risk assessment on a pesticide, a variety of toxicity information, including potential for noncancer effects (e.g., neurotoxicity, developmental and reproductive toxicity, 
immunotoxicity, etc) and carcinogenicity, are considered in determining whether to register a pesticide and what requirements for use of the pesticide need to be in place to protect human health. The simple fact of being listed here does not imply that the pesticide poses a significant cancer hazard to the public from use.

Three very important points:

1. This list does not consider exposure.

2. This list is not intended to be used outside an individual chemical's full assessment.

3. Inclusion on the list does not indicate a cancer hazard to the public from use.

That being said, this list identifies just under 50 pesticides that would be triggered.  Oddly enough, about 1/3 of them don't have US registrations, aren't legally approved for use in the US, yet are banned anyway.  Not only has the County (through its municipality Takoma Park, see below) misused the list, but it has done so against the advice of EPA.

Interestingly enough, this is an expansion from past efforts in the County to ban pesticides, where there is currently a ban in Takoma Park on lawn care products on both public and private property. It should be noted that the TP ban contains criteria taken from foreign jurisdictions, rather than from EPA (including a list of potential "endocrine disruptors" from unknown, uncited sources within the European Union).  This approach of incorporating multiple source of "chemical lists" of varying quality and using often non-transparent, non-reproducible methods is poor and fails to recognize exposure as an essential facet of "risk."  There is no risk if there is no exposure, or if the exposure is negligible relative to the levels known to cause adverse health outcomes.  

The TP pesticide ban for residents kicks in January 1, 2015.  This may be in fact the only such County-level pesticide ban on cosmetic uses in the US.  (And not surprising, Maryland is one of a handful of states that allow local governments to enact more stringent pesticide laws.)  

Similar bans have been enacted by several municipalities and provinces in Canada and, in some case, led to the public reacting negatively to unkempt and/or mismanaged public green spaces.  In short, it is unclear that banning use of pesticides in public spaces improves the usability of the space and it is unclear what the public health benefit is (given prior EPA full assessment of each compound that includes the rate at which it is applied).

USDA to provide $4+ million in technical and financial assistance to improve honey bee health

USDA press release included below in its entirety... this is building momentum from last week's meetings of both the North American Pollinator Protection Campaign as well as the USDA Forage & Nutrition Summit.

USDA to Provide $4 million For Honey Bee Habitat

Announcement Builds on Previous Investment in Michigan, Minnesota, North Dakota, South Dakota and Wisconsin

WASHINGTON, Oct.29, 2014 – Agriculture Secretary Tom Vilsack announced today that more than $4 million in technical and financial assistance will be provided to help farmers and ranchers in the Midwest improve the health of honey bees, which play an important role in crop production.

"The future of America's food supply depends on honey bees, and this effort is one way USDA is helping improve the health of honey bee populations," Vilsack said. "Significant progress has been made in understanding the factors that are associated with Colony Collapse Disorder and the overall health of honey bees, and this funding will allow us to work with farmers and ranchers to apply that knowledge over a broader area."

An estimated $15 billion worth of crops is pollinated by honey bees, including more than 130 fruits and vegetables. USDA's Natural Resources Conservation Service (NRCS) is focusing the effort on five Midwestern states: Michigan, Minnesota, North Dakota, South Dakota and Wisconsin. This announcement renews and expands a successful $3 million pilot investment that was announced earlier this year and continues to have high levels of interest. This effort also contributes to the June 2014 Presidential Memorandum – Creating a Federal Strategy to Promote the Health of Honey Bees and Other Pollinators, which directs USDA to expand the acreage and forage value in its conservation programs.

Funding will be provided to producers through the Environmental Quality Incentives Program (EQIP). Applications are dueFriday, November 21.

From June to September, the Midwest is home to more than 65 percent of the commercially managed honey bees in the country. It is a critical time when bees require abundant and diverse forage across broad landscapes to build up hive strength for the winter.

The assistance announced today will provide guidance and support to farmers and ranchers to implement conservation practices that will provide safe and diverse food sources for honey bees. For example, appropriate cover crops or rangeland and pasture management may provide a benefit to producers by reducing erosion, increasing the health of their soil, inhibiting invasive species, and providing quality forage and habitat for honey bees and other pollinators.

This year, several NRCS state offices are setting aside additional funds for similar efforts, including California – where more than half of all managed honey bees in the U.S. help pollinate almond groves and other agricultural lands – as well as Ohio and Florida.

The 2014 Farm Bill kept pollinators as a high priority, and these conservation efforts are one way USDA is working to help improve pollinator habitat.

USDA is actively pursuing solutions to the multiple problems affecting honey bee health. The Agricultural Research Service (ARS) maintains four laboratories across the country conducting research into all aspects of bee genetics, breeding, biology and physiology, with special focus on bee nutrition, control of pathogens and parasites, the effects of pesticide exposure and the interactions between each of these factors. The National Institute of Food and Agriculture (NIFA) supports bee research efforts in Land Grant Universities. The Animal and Plant Health Inspection Service (APHIS) conducts national honey bee pest and disease surveys and provides border inspections to prevent new invasive bee pests from entering the U.S. The Farm Service Agency (FSA) and NRCS work on improved forage and habitat for bees through programs such as the Conservation Reserve Program (CRP) and EQIP. The Forest Service is restoring, improving, and/or rehabilitating pollinator habitat on the national forests and grasslands and conducting research on pollinators. Additionally, the Economic Research Service (ERS) is currently examining the direct economic costs of the pollinator problem and the associated indirect economic impacts, and the National Agricultural Statistics Service (NASS) conducts limited surveys of honey production, number of colonies, price, and value of production which provide some data essential for research by the other agencies.

For more on technical and financial assistance available through conservation programs, visitwww.nrcs.usda.gov/GetStarted or a local USDA service center.

Update on proposed WOTUS rule

This week, over 30 supporting documents were posted to EPA's proposed Waters of the US (WOTUS) rule docket.

There will be additional documents placed in the docket.  Tomorrow, EPA will announce (in the Federal Register) availability of its Science Advisory Board final peer review of the EPA’s draft report "Connectivity of Streams and Wetlands to Downstream Waters: A Review and Synthesis."  It is entirely possible that it could appear at the SAB reports web site prior to posting in the FR docket.

The rule is open for comment until November 14.

Pesticide industry reformulates products in response to CA regulations

The pesticide industry is beginning to reformulate its products in response to a number of regulatory topics related to spray drift, volatilization and VOC content of formulations.  The Israeli-based company Adama, formerly Makhteshim Agan of North America, has recently announced its Voxien line of products, which includes low-VOC formulations of the compounds that are anticipated to be restricted in California next year.  (See my past coverage of this issue here.)  In addition to restriction on VOCs (as mandated by the State Implementation Plan), there are other regulatory shifts in how EPA will handle spray drift and volatilization.  (See my past coverage here.)

Valent USA also announced this week that it would market a new low VOC plant growth regulator.

More formulation changes from more companies shouldn't be a surprise; however, this is no simple matter.  Switching to a different source of an inert ingredient (VOCs are inert ingredients in pesticide formulations) can involve changes in the supply chain, changes to the formulation process, as well as paperwork (and associated approval timelines) at EPA.  What is most interesting about these moves is that appear to be prompted by a switch in a single state's regulatory needs (albeit California is an awfully big market for all crop protection companies!) ... that power of this state in shaping agricultural chemical policy is not be denied.