ELSEVIER Use of intermediate end-points to prevent long-term outcomes * Toxicology Letters Toxicology Letters 77 (1995) 121-125 A. Mutti zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPON Laboratory of Industrial Toxicology, University of Parma, Parma. Italy Accepted 13 January 1995 zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONM AbShWt Biomarkers may be very useful to assess and control the risk of long-term outcomes associated with exposure to industrial chemicals. Even when dose-effect and dose-response relationships have been demonstrated, the process of standard setting and the definition of ‘safe’ exposure levels is hampered by: (i) the arbitrary nature of attempts to distinguish acceptable from unacceptable effects; (ii) the difficulties in assessing the prognostic value of observed changes; (iii) the in:tluence of the study power on statistically defined thresholds. Integration of epidemiological fin- dings with mechaniistic studies is necessary to assure confidence in risk assessment and to undertake sound risk man- agement. Keyword: Biomark.ers;Risk assessment; Health effects; Hydrocarbons; Chromium; Cancer; Kidney zyxwvutsrqponmlkjihg 1. Introduction Risk assessment is - or should be - a scientific process providing a basis for risk management, that is for action and regulations aimed at protec- ting human health. Relevant outcomes to be prevented include well-defined clinical manifesta- tions occurring during or shortly after exposure to specific agents as well as multifactorial diseases ap- pearing after a long silent period in susceptible subgroups of the exposed population. Biomarkers may be useful to understand the nature and extent * As the Editor of this book, the author decided not to publish a full paper. However, an extended abstract of his pres- entation at the meeting is included to ensure that the Proceed- ings provide a record of what has been discussed. of human exposure to industrial chemicals, to identify susceptible individuals, and to detect adverse effects on groups at risk. Although biomarkers are surrogate measures of something difficult or impossible to measure (be- cause of theoretical or practical limitations), they may provide quantitative information relevant to one or more components of risk assessment: haz- ard identification, dose-response evaluation, expo- sure assessment, and risk characterisation [l]. Research on biomarkers is rapidly generating a large amount of data measuring intermediate end- points occurring probably after exposure and possibly before illness. Increased sensitivity in depicting exposure and biological effects gives rise to 3 basic questions that science and society must address before any action or even priority setting 03784274/95/$09.50 0 1995 Elsevier Science Ireland Ltd. All rights reserved SSDI 0378-4274(95)03281-O