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.