New Toxicology Tools and the Emerging Paradigm Shift in Environmental Health Decision-Making

Abstract

BACKGROUND: Numerous types of rapid toxicity or exposure assays and platforms are providing information relevant to human hazard and exposure identification. They offer the promise of aiding decision-making in a variety of contexts including the regulatory management of chemicals, evaluation of products and environmental media, and emergency response. There is a need to consider both the scientific validity of the new methods and the values applied to a given decision using this new information to ensure that the new methods are employed in ways that enhance public health and environmental protection. In 2018, a National Academies of Sciences, Engineering, and Medicine (NASEM) workshop examined both the toxicological and societal aspects of this challenge. OBJECTIVES: Our objectives were to explore the challenges of adopting new data streams into regulatory decision-making and highlight the need to align new methods with the information and confidence needs of the decision contexts in which the data may be applied. METHODS: We go beyond the NASEM workshop to further explore the requirements of different decision contexts. We also call for the new methods to be applied in a manner consistent with the core values of public health and environmental protection. We use the case examples presented in the NASEM workshop to illustrate a range of decision contexts that have applied or could benefit from these new data streams. Organizers of the NASEM workshop came together to further evaluate the main themes from the workshop and develop a joint assessment of the critical needs for improved use of emerging toxicology tools in decision-making. We have drawn from our own experience and individual decision or research contexts as well as from the case studies and panel discussions from the workshop to inform our assessment. DISCUSSION: Many of the statutes that regulate chemicals in the environment place a high priority on the protection of public health and the environment. Moving away from the sole reliance on traditional approaches and information sources used in hazard, exposure, and risk assessment, toward the more expansive use of rapidly acquired chemical information via in vitro, in silico, and targeted testing strategies will require careful consideration of the information needed and values considerations associated with a particular decision. In this commentary, we explore the ability and feasibility of using emerging data streams, particularly those that allow for the rapid testing of a large number of chemicals across numerous biological targets, to shift the chemical testing paradigm to one in which potentially harmful chemicals are more rapidly identified, prioritized, and addressed. Such a paradigm shift could ultimately save financial and natural resources while ensuring and preserving the protection of public health. https://doi.

US EPA's regulatory pesticide evaluations need clearer guidelines for considering mammary gland tumors and other mammary gland effects

“…While high throughput in vitro assays may be helpful for prioritization, there are many limitations that should be kept in mind ( Ginsberg et al, 2019 ; Krewski et al, 2020 ). For example, the assays typically don’t have metabolic capacity, which can lead to false positive and negative results.…”

“…US EPA’s ToxCast chemical screening program has tested many pesticides for these endpoints using high and medium-throughput in vitro assays that use a variety of human cell lines such as MCF-7 breast cancer and H295R adrenocortical carcinoma cells ( Thomas et al, 2019 ). These publicly-available data are an important resource despite the known limitations of in vitro testing such as the lack of metabolic capability of cells tested, influence of chemical properties affecting bioavailability, uncertain relevance of cell lines used in in vitro assays to normal tissue, and uncertainty in extrapolating effects across tissues or even multiple cell types in a single tissue ( Ginsberg et al, 2019 ; Krewski et al, 2020 ).…”

Rapid hazard characterization of environmental chemicals using a compendium of human cell lines from different organs

“…Notwithstanding the need for diverse high-throughput in vitro data streams to rapidly inform hazard identification and to fill the knowledge gap for chemicals with minimum toxicity data, challenges remain about their use in prioritization and screening level assessment strategies as well as tradeoffs between speed and uncertainty ( Paul Friedman et al, 2020 ). For instance, while high throughput screening data could play key roles in decision-making for emergency response, there are many limitations with respect to predicting chemical fate and effects in the environment, challenges that might lead to potentially missed hazards ( Ginsberg et al, 2019 ). Furthermore, there is also uncertainty in the extrapolation from in vitro bioactivity to in vivo toxicity ( Bell et al, 2018 ), and gaps exist in the cell-based in vitro screening and potential effects on human health since most cell assay endpoints are still related to cytotoxicity and non-specific effects ( Judson et al, 2016 ).…”

Risk Characterization of Environmental Samples UsingIn VitroBioactivity and Polycyclic Aromatic Hydrocarbon Concentrations Data

“…Examples over the last decade include applications to hazard identification of oil dispersant formulations (Judson et al, 2010), environmental samples (Blackwell et al, 2017(Blackwell et al, , 2019Escher et al, 2018;Horzmann et al, 2017;Neale et al, 2020), petroleum substances (Grimm et al, 2016;Kamelia et al, 2019), and botanicals (Catlin et al, 2018). The high-throughput format of in vitro assays allows for rapid testing, and it has been suggested that additions of in vitro bioactivity data to mixture risk assessment may hold promise in reducing uncertainties (Drakvik et al, 2020;Ginsberg et al, 2019). It has also been posited that cell-based bioassays can be used in support of environmental quality standards (Escher et al, 2018).…”