Low-level chemical sensitivity: a perspective from behavioral toxicology

Area of Science:

• Environmental toxicology
• Neurobehavioral toxicology
• Risk assessment methodology

Background:

• Traditional risk assessment, primarily designed for cancer, is ill-suited for evaluating neurobehavioral toxicants due to multiple endpoints.
• Existing methods struggle with low-level chemical sensitivity, Multiple Chemical Sensitivity (MCS), and Sick Building Syndrome (SBS) due to the lack of a single, measurable causative agent.
• Current toxicological assessments often overlook subtle neurobehavioral effects, particularly those induced by substances like food additives.

Purpose of the Study:

• To explore the limitations of conventional risk assessment models for neurobehavioral toxicants and conditions like MCS.
• To propose and evaluate alternative methodologies for assessing low-level chemical sensitivity and neurotoxicity.
• To identify optimal experimental designs and behavioral criteria for studying subtle neurotoxic effects.

Main Methods:

• Examining the applicability of existing risk assessment frameworks to neurobehavioral toxicants.
• Proposing the use of a 'miniature work situation' for evaluating sustained performance in the presence of target chemicals.
• Advocating for experimental designs emphasizing individual response consistency, particularly in subjects reporting low-level sensitivity.

Main Results:

• Neurotoxic risk assessment offers advantages over cancer risk assessment due to less uncertainty in dose extrapolation.
• Individual response consistency is a more informative criterion than large-sample significance tests for initial studies of low-level sensitivity.
• A significant proportion of subjects may not exhibit sensitivity, making individual consistency a key factor in identifying true effects.

Conclusions:

• Adapting risk assessment for neurobehavioral toxicants requires a shift from traditional models, focusing on subtle endpoints and individual responses.
• Experimental designs that prioritize consistency and utilize controlled exposure scenarios (e.g., miniature work situations) are crucial for advancing research on MCS and SBS.
• Future research should incorporate sensitive neurobehavioral measures to accurately assess the toxicity of various substances, including food additives.