Key Toxicology Risk Assessment Methods for Evaluating Chemical Safety

Traditional Toxicity Testing Approaches

In Vivo Animal Testing

The traditional paradigm in toxicity testing consists of in vivo toxicology, where compounds are tested in various and usually high concentrations against tens or even hundreds of rodents or other animals. (Koutsoukas et al., 2016)

This approach is not feasible in modern toxicological research due to the large number of chemicals that need to be tested, the high cost of animal models, low throughput readouts, ethical issues, and poor extrapolability to humans. (Koutsoukas et al., 2016)

Alternative Toxicity Assessment Methods

In Vitro Cell-Based Assays

Alternative avenues are currently being explored for chemical risk assessment using in-vitro approaches, such as human cell-based assays and high-throughput screening (HTS) technologies. (Koutsoukas et al., 2016)

Quantitative high-throughput screening (qHTS) has emerged as a powerful and efficient way to alleviate the limitations of single-point concentration HTS screening and allow for more comprehensive evaluation of chemical toxicity. (Koutsoukas et al., 2016)

In Silico Computational Modeling

In silico approaches can be applied to generate testable hypotheses for chemicals and direct experimentation toward the most likely unwanted interactions, which can then be validated or invalidated. (Koutsoukas et al., 2016)

Computational approaches could provide more efficient utilization of limited experimental resources and become 'the next big thing' as decision-making tools during the development and risk assessment stages. (Koutsoukas et al., 2016)

Adverse Outcome Pathways (AOPs)

AOPs are a conceptual framework that describes a sequential chain of causally linked events at different levels of biological organization that lead to an adverse health or ecotoxicological effect. (Moné et al., 2020)

AOPs can guide the selection of relevant non-animal methods (NAMs) for hazard assessment and help integrate the information from different NAMs into a coherent toxicological evaluation. (Moné et al., 2020)

Integrated Approaches to Testing and Assessment (IATA)

IATA is a structured approach used for hazard identification, hazard characterization, and/or safety assessment that integrates and weighs all relevant existing evidence and guides the targeted generation of new data, within a specified regulatory framework, to inform regulatory decision-making regarding potential hazard and/or risk. (Moné et al., 2020)

IATA combines different information sources, including physicochemical properties, (Q)SAR, read-across, in vitro data, and targeted testing, to assess the safety of chemicals. (Moné et al., 2020)

Next-Generation Risk Assessment (NGRA)

NGRA is a safety assessment approach that uses new approach methodologies (NAMs), such as in vitro assays and computational models, to quantify chemical hazards without relying on animal testing. (Moné et al., 2020)

NGRA combines NAM-based hazard quantification with defined exposure scenarios and exposure models to assess the safety of chemicals. This approach aims to provide a more comprehensive and reliable assessment of chemical safety compared to traditional methods. (Moné et al., 2020)

Key Considerations in Toxicology Risk Assessment

Regulatory Challenges

Safety regulatory agencies are currently dealing with two major challenges:

1. The increased number of chemicals that need to be tested for potential harmful effects on human health.
2. The time and cost required to evaluate those chemicals. (Koutsoukas et al., 2016)

Alternative and more efficient toxicological risk assessment methods are in high demand to address these challenges.

Tox21 Consortium

The Toxicology in the 21st Century (Tox21) consortium is a major collaborative effort involving several agencies, including the National Institutes of Health (NIH), the Environmental Protection Agency (EPA), and the Food and Drug Administration (FDA), to develop and evaluate alternative risk assessment methods. (Koutsoukas et al., 2016)

The Tox21 consortium has screened a collection of 10,000 compounds composed of environmental chemicals and approved drugs for interference in biochemical pathways and released the data for crowdsourcing analysis. (Koutsoukas et al., 2016)

Integrating Multiple Approaches

Effective toxicology risk assessment often requires the integration of multiple methods, including in vitro cell-based assays, in silico computational modeling, and adverse outcome pathways (AOPs).

By combining these approaches, researchers can generate more comprehensive and reliable assessments of chemical safety, addressing the limitations of individual methods. (Moné et al., 2020)

Quality Assurance and Data Management

Proper quality assurance and data management are crucial for the successful implementation of new toxicology risk assessment methods. This includes optimizing scientific and regulatory advisory processes, as well as ensuring the practical applicability of the approaches for regulatory decision-making. (Moné et al., 2020)