Framework for gender differences in human and animal toxicology.

Area of Science:

• Toxicology and Epidemiology
• Pharmacology
• Biology

Background:

• Sex and gender differences are fundamental in biology but inadequately addressed in toxicology and epidemiology.
• Generalizations about species' responses to xenobiotics often ignore male/female variations.
• Historically, regulatory guidelines and study designs have excluded females, limiting understanding of sex-specific effects.

Purpose of the Study:

• To provide a framework for analyzing sex and gender differences in xenobiotic exposure and effects.
• To highlight the importance of considering sex and gender in toxicological and epidemiological research.
• To emphasize the need for translational research integrating laboratory findings with clinical observations.

Main Methods:

• Development of a framework analyzing exposure, toxicokinetics, toxicodynamics, and modulating influences.
• Review of existing literature on sex differences in response to xenobiotics.
• Discussion of genetic and hormonal factors influencing sex-based variations.

Main Results:

• Men and women exhibit differing vulnerabilities to xenobiotics, starting with exposure opportunities.
• Toxicokinetic differences are primarily observed in metabolism, with less evidence for absorption variations.
• Lifestyle, psychosocial, and hormonal factors significantly modify xenobiotic kinetics and responsiveness.
• Both sex hormone-dependent and independent mechanisms contribute to observed sex differences.

Conclusions:

• Sex and gender are critical determinants of xenobiotic effects and require explicit consideration in research and practice.
• Future studies should employ balanced gender designs and analyze data for sex interactions.
• Further research is needed to disentangle the complex interplay of genetic and hormonal influences on sex differences in toxicology.