Tuesday, 27 April, 2021
10:00AM – 11:30 AM ET
Register here: https://zoom.us/webinar/register/WN_iSuRHKyQQfeYETZUD9L68g
American Society for Cellular and Computational Toxicology and European Society for Toxicology in Vitro
Marissa B. Kosnik, PhD, Technical University of Denmark
Shaun D. McCullough, PhD, US Environmental Protection Agency
Gary Marchant, PhD, JD, Sandra Day O’Connor College of Law, Arizona State U.
Kirk T. Hartley, JD, ToxicoGenomica and LSP Group LLC
Presentation Title: Legal and Policy Challenges in Agency Regulatory Use of NAMs
Presenter: Gary Marchant, PhD, JD
U.S. regulatory agencies are exploring use of new approach methodologies (NAMs) to make their regulatory actions more timely, accurate, and informed. However, reliance on NAMs in regulatory decision-making presents policy and legal hurdles. This presentation will discuss such hurdles, using real-life examples. The first challenge is validation, including whether an agency must use the formal interagency coordinating committee on the validation of alternative methods (ICCVAM) process or use a more informal ad hoc validation process to validate a new NAM. A case study of this issue will be EPA’s proposed use of NAMs to refine the inhalation risk assessment for point of contact toxicity for Syngenta’s fungicide chlorothalonil, which the agency identified as setting a precedent for future validation and use of NAMs under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). The second challenge is a policy one, in which the agency must satisfy multiple external stakeholders, including Congress, reviewing courts, industry, citizen groups, and the media. The EPA Genomics Policy and the EPA Endocrine Disruptor Screening Program will be used as case studies. The third challenge is legal, and in particular the requirement that agencies act consistently and according to precedent, as well as in compliance with statutory requirements. In particular, agencies must be prepared for legal challenges to departures from traditional methods. The balance between precedent and novel science will be discussed using the Chlorine Chemistry Council v. EPA case (206 F.3d 1286 (D.C. Cir. 2000)) regarding attempts to depart from the linear, non-threshold model traditionally used to set a zero level (non-threshold) maximum contaminant level for chloroform as an example. To achieve the full benefits of NAMs, agencies must be prepared to proactively address the validation, policy and legal challenges associated with the use of new methods. The concepts and examples discussed here will give attendees greater insight into the legal implications and requirements involved in the use of NAMs for chemical testing and registration.
Presentation Title: Case Studies of Actual Uses of NAMs in Civil Litigation Involving Diseases/Conditions
Presenter: Kirk T. Hartley, JD
Litigants in civil law cases between private parties (e.g. product liability and personal injury cases) are increasingly offering evidence generated through new approach methodologies (NAMs). As with the use of all new technologies, the presentation of NAMs-based data as evidence in legal proceedings is subject to considerable scrutiny by scientific and legal experts that often have both divergent opinions and interests. The field needs additional multidisciplinary efforts so that litigants and courts 1) correctly understand and utilize technical information in court, and 2) appreciate the long term power of NAMs to provide objective, mechanistic data useable to investigate and reveal the etiology of disease at the individual level rather than focusing on cohorts. This presentation will use case studies to focus on actual successes and failures of the use of NAMs data in such cases, including real and erroneous concerns about privacy, factual and legal issues regarding whether research data is subject to the legal “discovery” process, and tensions between traditional epidemiology and today’s NAMs, including uncertainty about proper methods for differential diagnosis, and the application of Bradford Hill criteria to establish causality. The first case study will discuss the presentation of data in dose-response and gene x environment (GxE) interaction studies using germline and conditional transgenic mice as evidence in asbestos and glyphosate litigation. Second, a set of case studies involve use of whole genome or gene panel sequencing as the predicate for using systems biology analyses as evidence in disputes over whether plaintiffs’ diseases were caused by exposures (e.g., vaccines, drugs, pesticides, asbestos, benzene, PFOA/PFAS, and radiation) or genetic/epigenetic/molecular factors. A third set of case studies will examine litigation on the consequences of the use or non-use of in vitro, in silico and in vivo investigations to reveal and attribute “signature patterns” of mutations/epimutations in tumors arising from exposures to toxins (e.g., 79 toxins studied, including drugs, radiation, aldehydes, and metal salts) and attribute the presence or absence of combinations of inherited mutations to birth defects. From the case studies presented, attendees will gain insight into considerations for the use of NAMs data in legal cases.
The presentations will be followed by a moderated panel discussion and active Q&A. Put on your thinking caps and come prepared to participate in this unique, compelling session!