Leveraging ToxCast data and protein sequence conservation to complement aquatic life criteria derivation

Area of Science:

• Environmental Toxicology
• Ecotoxicology
• Risk Assessment

Background:

• Traditional aquatic life criteria (ALC) derivation is data-intensive, often lacking sufficient in vivo data for many chemicals.
• Provisional values are needed to guide stakeholders while comprehensive data are gathered for rigorous ALC.
• New Approach Methodologies (NAMs) offer potential for generating such provisional data.

Purpose of the Study:

• To assess the feasibility of using NAMs, specifically ToxCast, for deriving provisional aquatic life criteria.
• To estimate chemical potency and elucidate toxicity mechanisms using NAM data.
• To evaluate the species relevance of identified toxicity pathways for potential ALC waiver considerations.

Main Methods:

• ToxCast data were used to derive points of departure (PODs) based on activity concentration percentiles.
• Mechanistic inferences were drawn from ToxCast active target hits.
• Taxonomic conservation of toxicity pathways was assessed using SeqAPASS.

Main Results:

• ToxCast-derived PODs for nine chemicals showed reasonable alignment with existing aquatic benchmarks (USEPA, DOE).
• Six of nine chemicals were within a factor of 10, and eight of nine within a factor of 100.
• Toxicity pathways identified through NAMs reflected findings from in vivo studies.

Conclusions:

• NAM data, such as from ToxCast, show potential for complementing traditional ALC derivation.
• This approach can aid in chemical prioritization and resource management, especially when in vivo data are limited.
• Preliminary findings support the use of NAMs for provisional criteria development.