• Report of the Bilthoven Symposium: Advancement of epidemiological studies in assessing the human health effects of immunotoxic agents in the environment and the workplace

      Loveren H van; Germolec D; Koren HS; Luster MI; Nolan C; Repetto R; Smith E; Vos JG; Vogt RF; LPI-RIVM; National Institute of Environmental Health Sciences NIEHS(USA); American Crop Protection Association ACPA(USA); Environmental Protection Agency EPA(USA); Centers for Disease Control and Prevention CDCP(USA); European Commission EC(Belgie); World Resources Institute WRI(USA); World Health Organization WHO(Zwitserland); Centers for Disease Control CDC(USA) (1998-07-22)
      A scientific symposium 'Epidemiology of Immunotoxicity' was held in Bilthoven, the Netherlands, on November 12-14, 1997. This symposium was stimulated by publication of the report of a 1994 WHO/IPCS Task Group meeting on principles and methods for assessing direct immunotoxicity associated with exposure to chemicals (WHO, 1996), a report by the World Resources Institute (WRI 1996) that raised concern about the immunosuppressive effects of pesticides on exposed populations in developing countries, and a workshop on 'Environment and Immunity' organized by the European Union (EU, 1997). A common theme among these reports was the need for well designed epidemiological studies on immunotoxicity. Experts in epidemiology, clinical immunology, and immunotoxicology who participated were asked to reach consensus on the most useful approaches to assess immunotoxic effects in humans. The symposium demonstrated the benefits which can be derived from 'cross-fertilization' - a meeting of the minds and sharing of ideas - i.e. the best product in terms of design, conduct, and interpretation of a complex scientific issue. The meeting concluded that epidemiology is an essential method for assessing immunotoxicity in humans. Every epidemiologic study should have valid measures of exposures, confounders and health endpoints. Although questionnaires and diaries are important and valuable tools in epidemiology, direct and quantitative biological measures are preferred. When possible, a longitudinal study design in which study subjects are observed over a time sufficient to assess the health outcomes associated with immunotoxic exposures and alterations in immune functions is preferable. While such studies are most often prospective, retrospective studies, using banked specimens from individuals who develop immune related disease, would be useful if exposure assessment is objective and quantifiable. A longitudinal study design may be most suitable where infections are the health consequences of immunotoxicity, but is much more time consuming and costly when the expected health outcome is cancer. Two prime biologic measures were identified as particularly valuable for assessment of immunotoxicity in epidemiological studies. First, the immune system is most efficiently and accurately assessed for the influence of chemical exposure on direct hypersensitivity responses by the skin prick test, or antigen specific IgE ELISA or RAST tests. Second, for suppression of immune function, the system is best assessed by vaccination with an antigen to which no prior exposure has occurred. It was generally accepted that if children, with defined high exposures, respond to vaccination with similar titers as non-exposed children, and there is no clinical evidence of increased numbers of infections, the agent is most likely not immunotoxic in humans. A strong recommendation is therefore to make a greater use of (pediatric) vaccination programs. While this approach focuses on the children, it can also be applied to the adult population. These measures are also most consistent with observations in animal studies as the most predictive endpoint - i.e. the primary antibody response to a T-dependent antigen. Studies of childhood infectious diseases and malignancies may be emphasized in developing countries, whereas studies of allergic and malignant diseases may be emphasized in developed countries, reflecting the most critical health concerns in the respective types of countries.