Resource requirements for ecotoxicity testing: A comparison of traditional and new approach methods

Abstract

Toxicity testing is under transformation as it aims to harness the potential of New Approach Methods (NAMs) as alternative test methods that may be less resource-intensive (i.e., fewer animals, cheaper costs, quicker assays) than traditional approaches while also providing more data and information. While many stakeholders are of the opinion that this unfolding transformation holds significant promise as a more efficient and ethical way forward, few studies have compared the resources required for NAMs versus those needed for traditional animal-based toxicity tests, particularly in the field of ecotoxicology. The objective was to compare resources needed for traditional animal-based ecotoxicity tests versus alternative tests using emergent NAMs. From a bibliometric review, we estimate that traditional tests for a single chemical cost $118,000 USD, require 135 animals, and take 8 weeks. In comparison, alternative tests cost $2,600, require 20 animals (or none), and take up to 4 weeks to test 16 (to potentially hundreds of) chemicals. Based on our analysis we conclude that NAMs in ecotoxicology can be more advantageous than traditional methods in terms of resources required (i.e., monetary costs, number of animals needed, and testing times). We note, however, that the evidence underpinning these conclusions is relatively sparse. Moving forward, groups developing and applying NAMs should provide more detailed accounts of the resources required. In addition, there is also a need for carefully designed case studies that demonstrate the domain of applicability of NAMs (and make comparisons to traditional tests) to ultimately build confidence among the user community.

Applicability of OECD TG 201, 202, 203 for the aquatic toxicity testing and assessment of 2D Graphene material nanoforms to meet regulatory needs

“…Testing with fish embryo's using the OECD TG 236 Fish Embryo Acute Toxicity (FET) test and also the newly published OECD TG 249 for acute toxicity assessment using fish cell lines both represent alternative standardised tests that can be used in a weight of evidence (WoE) approach for fish acute toxicity and hazard assessment (Sobanska et al, 2018). They also represent new approach methodologies (NAMs) for fish acute toxicity assessment that would save time and resources (Mittal et al, 2022). Incorporating such standardised NAM tests into an integrated approach to testing and assessment (IATA) contributes to increasing certainty/reliability while also advocating for 3Rs and alternatives to animal testing (Paparella et al, 2021).…”

A Benchmark Dataset for Machine Learning in Ecotoxicology

“…Fingerprints are fixed-length, binary vectors where each bit indicates presence ("1") or absence ("0") of a substructure. MACCS, consisting of 166 publicly available bits, PubChem, consisting of 881 bits, and ToxPrint, consisting of 729 bits, are substructure keys-based, i.e., each bit corresponds to a predefined substructure 2 . The Morgan fingerprint is a circular fingerprint based on all fragments that can be extracted within a bond radius around each atom of the molecule.…”

“…A recent pre-print estimates the global annual usage of fish and birds to range between 440,000 and 2.2 million individuals at a cost upwards of $39 million p.a. 2 . With over 200 million substances in the archive of the Chemical Abstracts Service (CAS, www.cas.org) and more than 350,000 chemicals and mixtures currently registered on the market worldwide 3 , chemical hazard assessment is a major challenge.…”

“…In fact, its inclusion would constitute a form of data leakage, since, e.g., labeling a substance group as biocides would correlate well with higher toxicity towards certain species, but the information was not transmitted through a chemical feature but through this label. 2 See these links for the definition of each MACCS bit and PubChem bit.…”

Machine learning-based prediction of fish acute mortality: Implementation, interpretation, and regulatory relevance

“…Acute (i.e., short-term) fish mortality tests are required for chemicals with an import and production volumes of more than 10 tons per annum and are standardized through the OECD test guideline (TG) 203 2 . The global use of birds and fish was estimated to range between 440,000 and 2.2 million individuals at a cost upwards of $39 million per annum 3 . Consequently, reducing the use of animals and, more specifically, fish acute toxicity testing has a high priority in chemical hazard assessment, both from an economical and ethical perspective.…”