Reference dose (RfD): the possible impact of hormesis

Area of Science:

• Environmental toxicology
• Risk assessment science
• Chemical safety evaluation

Background:

• Hormesis, a biphasic dose-response, presents challenges in traditional toxicological risk assessment.
• Establishing safe exposure limits (reference dose, RfD) for chemicals with hormetic effects requires careful consideration.
• Previous risk management frameworks may not adequately address hormesis.

Purpose of the Study:

• To explore the challenges in setting a reference dose (RfD) for a chemical exhibiting hormesis.
• To derive human dose-response curves from animal data for both average and sensitive populations.
• To discuss scientific and policy questions relevant to regulatory decision-making in hormesis cases.

Main Methods:

• Utilized animal data to derive dose-response curves for human populations.
• Applied principles of risk assessment to a hypothetical scenario involving a hormetic chemical.
• Reviewed scientific literature and policy considerations for regulatory dose (RgD) setting.

Main Results:

• Dose-response curves were extrapolated for average and sensitive human populations.
• Identified key scientific and policy uncertainties in RfD determination for hormetic substances.
• The concept of a 'regulatory dose' (RgD) was revisited as a potential approach.

Conclusions:

• Setting a regulatory dose (RgD) for hormetic chemicals necessitates addressing complex scientific and policy issues.
• Deriving human-relevant dose-response curves from animal data is crucial but involves uncertainties.
• Further development of risk assessment methodologies is needed for chemicals exhibiting hormesis.