Current concepts in the assessment of effects of metals in chronic low-level exposures--considerations of experimental and epidemiological evidence.

Human exposure to metals and their compounds may give rise to a number of adverse effects. Of particular interest are such effects that can be elicitated by chronic low-level exposure, since such exposures may occur in human populations both in the general environment and occupationally. The adverse effect that occurs at the lowest exposure has been termed the "critical effect" since it is critical in relation to preventive action aiming at limiting exposures to a safe level. When reviewing the present evidence on the toxicology of metals it becomes evident that "critical effects" may be related to various organ systems, disease categories and biochemical mechanisms of damage. A category of effects, which is of particular interest in relation to critical effects, is hypersensitivity (e.g. with dermal or respiratory manifestations). However conceptual recognition of this category of effects is as yet incomplete. Other important considerations are whether effects display threshold- or non-threshold type dose-response relationships, the latter category obviously being more likely to display a low incidence response at low dose exposure. In this context mutagenic, carcinogenic, developmental and reproductive toxicity of metals are of particular interest. Information on these types of effects compiled during previous meetings of the scientific committee on the toxicilogy of metals and recently updated, indicates that some compounds of arsenic, beryllium, cadmium, chromium and nickel may be regarded as carcinogenic for humans. Available evidence in experimental systems as well as in humans concerning effects of metallic compounds on male and female reproductive systems, congenital teratogenicity and perinatal toxicity as well as effects on the developing central nervous system indicates that such effects should be considered further in relation to critical effects for arsenic, cadmium, lead, mercury and their compounds.