SOT Spotlight: Q&A with Claire Mathis

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What is the title of your presentation?

Derivation of Adverse Deep Lung Effect Thresholds for α-Diketone Compounds.

What was the scope of your research?

We utilized the results from animal inhalation studies to develop daily time-weighted average (TWA) α-diketone effect thresholds for adverse bronchiolar and alveolar (i.e., deep lung) effects. The effect thresholds specifically refer to the airborne α-diketone concentrations below which there are minimal, if any, expectation for the onset of adverse deep lung effects in humans. Effect thresholds were identified through benchmark dose modeling and through a no-observed-adverse-effect-level (NOAEL) based on the animal studies. Human equivalent concentrations were then calculated using a TWA conversion factor and an appropriate dosimetric extrapolation factor.

What did you find?

Based on a two-year chronic and a 90-day subchronic diacetyl study, we determined TWA diacetyl effect thresholds for a 45-year occupational lifetime (4 ppm) and for an occupational tenure of 9 years or fewer (6 ppm). Information from an additional animal inhalation study, which compared the biological reactivity of diacetyl, 2,3-pentanedione, and 2,3-hexanedione, indicates that longer chain α-diketones (i.e., 2,3-pentanedione and 2,3-hexanedione) are even less biologically reactive than diacetyl. We therefore concluded that the effect thresholds for diacetyl were also applicable to longer chain diketones.

What are the next steps/what other research is needed?

These effect thresholds represent exposures levels at which we would not expect the onset of significant, adverse deep lung effects. These point of departure estimates can be used for risk assessments of worker cohorts who are occupationally exposed to the diketones, such as food flavoring and manufacturing workers.