[Can exposure to low doses have effects?].
This paper aims to discuss the scientific evidence to answer the question in the title. After a brief mention of the fundamental toxicological principles of risk assessment (hazard, exposure, susceptibility, risk), the concepts of dose-response, dose-effect and threshold-dose are presented. The difference between adverse effects with and those without a threshold is highlighted, together with the corresponding methodologies used in risk assessment for the definition of the limit values, i.e. the No Observed Adverse Effect Level (NOAEL) and Safety Factor (SF) method and the Virtually Safe Dose (VSD) method. The two methods correspond to two different types of effect, i.e. deterministic and stochastic, and to two different shapes of the dose-response curve at low doses. The various possible meanings (semantic, toxicological and practical) of the terms "low doses" are discussed: a dose (or concentration) may be low because it does not cause measurable adverse effects (as from Paracelsus' aphorism) or because it is too low to be (analytically) measurable or because it is close to or within the "normal" values of a reference population or because it is well below the exposure limit(s). These various concepts are presented also in relation with the controversial concept of "moderate risk" introduced by a recent Italian legislation (D. Lgs 25/02) on the protection of the workers against chemical risk. It would not be appropriate to set a level of risk simply based on the dose (or the level of exposure) without considering the two other components of risk, i.e. hazard and susceptibility, whose estimation also needs a careful and competent evaluation by the occupational physician. For a thorough discussion of the "moderate risk" concept see a specific paper in these Proceedings. So, clinical, epidemiological and toxicological evidence indicates that in some individuals, groups of the population or circumstances, adverse effects can be observed or expected even at low doses, at which the large majority of the population shows no effect. This is due to a number of factors including toxicological interactions, immunoallergic mechanisms, metabolic hypersusceptibility, both genetic (polymorphism) and acquired (phenotype), preexisting traits or diseases, living habits, diet and others. The Authors conclude therefore that to ensure the protection of all the workers' health and safety, the clinical, toxicological and epidemiological expertise of the occupational physician appears to be fundamental and unreplacable.
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Dipartimento di Medicina Sperimentale ed Applicata, Medicina del Lavoro e Igiene Industriale, Università degli Studi di Brescia.
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D004305:Dose-Response Relationship, Drug; D006801:Humans; D018570:Risk Assessment; D020711:Threshold Limit Values