Incorporating genetics and genomics in risk assessment for inhaled manganese: from data to policy

Abstract

Manganese is an essential nutrient, and a healthy human with good liver and kidney function can easily excrete excess dietary manganese. Inhaled manganese is a greater concern, because it bypasses the body's normal homeostatic mechanisms and can accumulate in the brain. Prolonged exposure to high manganese concentrations (>1mg/m(3)) in air leads to a Parkinsonian syndrome known as "manganism." Of greatest concern are recent studies which indicate that neurological and neurobehavioral deficits can occur when workers are exposed to much lower levels (<0.2mg/m(3)) of inhaled manganese in welding fumes. Consequently, researchers at NIOSH are conducting a risk assessment for inhaled manganese. Novel components of this risk assessment include an attempt to quantify the range of inter-individual differences using data generated by the Human Genome Project and experimental work to identify genetically based biomarkers of exposure, disease and susceptibility. The difficulties involved in moving from epidemiological and in vivo data to health-based quantitative risk assessment and ultimately enforceable government standards are discussed.

Fig. 1

Risk Assessment Paradigm. The standard Risk Assessment Paradigm (National Research Council, 1983) includes four phases moving from Hazard Identification through Risk Characterization. The paradigm was modified to show how genetics and genomics can be incorporated to improve policy development and decision-making.