The mismeasure of dermal absorption

Area of Science:

• Toxicology
• Dermal Absorption Science
• Exposure Assessment

Background:

• Dermal absorption experiments are commonly reported using fractional absorption.
• Fractional absorption is often dependent on skin loading conditions, leading to misinterpretation.
• Misinterpretation can result in inaccurate exposure estimations and threat assessments.

Purpose of the Study:

• To introduce a dimensionless group, the dermal number (N(DERM)), for interpreting dermal absorption phenomena.
• To provide a metric for distinguishing between flux-limited and delivery-limited dermal absorption conditions.
• To improve the accuracy of exposure assessments and threat evaluations related to dermal contact.

Main Methods:

• Proposed a dimensionless group (N(DERM)) representing the ratio of mass delivery to plausible absorptive flux.
• Analyzed conditions under high N(DERM) (flux-limited) and low N(DERM) (delivery-limited).
• Extended the logic to skin sampling and dermal toxicity testing scenarios.

Main Results:

• High N(DERM) indicates surplus supply (flux-limited), where fractional absorption depends on load and is not universally transferable.
• Low N(DERM) indicates delivery-limited conditions, where high fractional absorption is possible if not affected by depletion.
• The N(DERM) concept applies to skin sampling and toxicity testing, highlighting potential inaccuracies under specific conditions.

Conclusions:

• The proposed dermal number (N(DERM)) aids in the correct interpretation of dermal absorption experiments.
• Understanding N(DERM) is crucial for accurate exposure assessment, threat evaluation, and designing reliable toxicity tests.
• This metric helps prevent misinterpretations arising from the load-dependent nature of fractional absorption.