This blog is being shared under the SOT Secretary’s name as part of their official duties and should not be interpreted as their personal or professional opinions.
This blog was written by Talia Sager.
At the 2026 Poster Session “ADME/Toxicokinetics I,” I spoke with John Wambaugh, PhD, about his poster, “Route-Specific Variation of Systemic Bioavailability of Chemical Emissions,” and he shared fascinating insights into how the way a chemical enters the body dramatically shapes its potential health impact. Using high-throughput toxicokinetics (HTTK), specifically physiologically based toxicokinetic (PBTK) models, the study predicts how chemicals behave when absorbed through different exposure routes and explores why these differences matter for real-world risk assessment.
Dr. Wambaugh explained that two chemicals with the same external dose can lead to very different internal exposures depending on the pathway of entry, which he illustrated with an example he got from Mel Anderson, one of the earliest adopters of PBTK models. If you cut out a square foot of carpet from a smoker’s home, the nicotine embedded in the fibers could be enough to kill a person. But even if someone could somehow consume the entire carpet, he joked that it would require quite a lot of ketchup, the nicotine still wouldn’t be lethal because it isn’t bioavailable through the oral route. The chemical is present, but the body is not able to access it in a harmful way.
The study expands that concept across more than a thousand chemicals. The research team combined physiologically based toxicokinetic (PBTK) models with chemical-specific inputs to estimate steady-state plasma concentrations for multiple exposure pathways including oral ingestion, fume inhalation, and repeated dermal contact, as well as an aerosol dosimetry model paired with a gas-inhalation PBTK model for aerosol exposure. These parameters were either measured in vitro or predicted using quantitative structure-property relationship (QSPR) models, enabling simulations for over 1,500 compounds. Chemicals were then ranked using the Toxicological Prioritization Index (ToxPI) to visualize differences in route-specific bioavailability.
The results show broad variation. Some chemicals, like 2-tert-butylphenol, were predicted to be highly bioavailable across all routes, while others were nearly unavailable by one pathway and readily absorbed by another. The team also identified route-specific standouts, such as tridecane as the most bioavailable via fumes and 1,2-dimethyl-3-nitrobenzene for dermal exposure.
This study’s findings highlight that assessing chemical hazard requires understanding how people might be exposed, not just what chemical is present. These models help translate data from new approach methods for hazard into human-relevant doses and guide researchers toward the most important exposure pathways to investigate, ultimately supporting more accurate and actionable risk assessments.
This blog reports on the poster titled “Route-Specific Variation of Systemic Bioavailability of Chemical Emissions” that was shared during the 2026 SOT Annual Meeting and ToxExpo.
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