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Physiological factors predisposing to neurotoxicity

D E Ray1

  • 1Medical Research Council Toxicology Unit, Leicester, United Kingdom.

Archives of Toxicology. Supplement. = Archiv Fur Toxikologie. Supplement
|January 1, 1997
PubMed
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Individual susceptibility to toxic agents depends on absorption, metabolism, and elimination, not just target site interaction. Factors like physiological changes and disease states significantly influence toxicological responses.

Area of Science:

  • Toxicology
  • Environmental Health
  • Pharmacokinetics

Background:

  • Individual susceptibility to toxic agents is multifactorial.
  • Factors beyond primary target site interaction influence toxicological outcomes.

Purpose of the Study:

  • To elucidate the diverse factors influencing individual susceptibility to toxic agents.
  • To highlight the importance of pharmacokinetic and physiological variables in toxicology.

Main Methods:

  • Review and synthesis of existing toxicological principles.
  • Illustration with specific examples of agent-specific toxicities.

Main Results:

  • Absorption, distribution, metabolism, and elimination (ADME) critically affect toxicity.

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  • Physiological factors (e.g., work rate, blood flow) and adaptive responses vary susceptibility.
  • Developmental stage, genetic, nutritional, and disease states significantly modify toxic responses.
  • Examples include carbon monoxide, aminoglycosides, dinitrobenzene, nicotine, haloperidol, manganese, lead, hexane, and copper.

    • Conclusions:

    • Toxicological outcomes are highly individualized due to complex interactions.
    • Understanding these factors is crucial for accurate risk assessment and personalized medicine.