Exposure science and the exposome: an opportunity for coherence in the environmental health sciences.

摘要: The field of exposure science began with qualitative observations and quantitative measurements air contaminants to aid our understanding exposure–disease relationships. In fact, some the earliest writings that describe essence are found in Bernardino Ramazzini’s 1700 treatise on occupational diseases (Franco 1999). 1920s, scientists collaborated epidemiologists investigate workplace exposures as sources (Rappaport 2011). Between 1950s 1970, investigations expanded include pollutants ambient indoor water Following establishment U.S. governmental agencies 1970s regulate (Occupational Safety Health Administration) environment [U.S. Environmental Protection Agency (EPA)], paths diverged into those investigating settings By 1990s two groups had essentially parted ways, term “exposure science” was associated community personal (Lioy 2010; Ott 1990, 1995). Investigations total initially employed external chemicals can enter body by inhalation, ingestion, dermal contact (1970s), internal markers were added 1980s (Centers for Disease Control Prevention 2009; Hoffmann et al. 2000; Sexton 1995; Wallace 1985). 21st century, has increasingly embraced deterministic models predict levels diverse based categorical data (Cohen Hubal Georgopoulos Lioy 2006; 2010) measured biological fluids tissues (Georgopoulos 2009). In parallel above activities, during 1990s, molecular explored links between genetic environmental factors resulting biochemical or indicators possible ill health (biomarkers) individual subjects (Bonassi Au 2002). When completion human genome project 2000 made it feasible measure thousands polymorphic genes each subject, epidemiology focused determinants (Hindorff 2009). However, results these genome-wide association studies (GWAS) failed explain most variability (Manolio 2009), interest reemerged. But there no analog GWAS; is, we way characterizing totality a person’s exposures. This prompted Christopher Wild publish commentary defined “exposome” complement (Wild 2005). Recognizing humans exposed health-impairing agents from both pollution nonpollution change lifetime, indicated “… exposome encompasses life-course (including lifestyle factors) prenatal period onwards.” is powerful idea because considers lifetime history all experienced (e.g. pollution, radiation, diet) inflammation, infection, microbiome) Smith 2010). Thus, one imagine future which individuals’ exposomes contrasted diseased healthy populations epidemiology, over different life stages part personalized medicine (Nicholson 2006). either case, goal would be discover causes generate hypotheses regarding identification elimination reduction harmful exposures. If concept useful science, methods will needed characterize variability. Because arise sources, Rappaport generic approaches 2011; A “bottom-up” approach focus category exposure—including air, water, diet, lifestyle, etc.—to quantify contaminant summed categories estimate exposomes. appealing focuses same media have long been investigated leads logically interventions eliminating reducing this bottom-up require tremendous effort evaluate myriad largely unknown analytes various also miss important endogenous alternative “top-down” adopt untargeted omic features fluids, thus finds appeal who used biomonitoring assessing levels, albeit chemical-by-chemical basis. more efficient exogenous represented single specimen blood, example, encourage contrasts profiles much manner GWAS (Patel Omic a) indentify particular exposures, b) develop specific biomarkers high-throughput screens, c) determine exposure. Recent metabolomic applied top-down identify hitherto cardiovascular disease (Holmes 2008; Wang 2011). When examined objectively, scientific value offers discovering 2010), whereas encourages comprehensive analyses intervention prevention Indeed, envision long-term strategies embrace elements improving public health. Unfortunately, differentiation (air, soil/dust, etc.) (biological fluids) led an apparent disconnect competition monitoring modeling favor methods. encountering view summarized versus exposome.” counterproductive potentially deprives avenues vastly diversifying its pool relevant strengthening source-to-dose framework sciences. Rather than adopting defensive postures, exploit relative strengths Toward end, National Academy Sciences convene workshop December 2011 better integrate (Emerging Technologies Measuring Individual Exposomes, 8–9 2011, Washington, DC; information available at http://dels.nas.edu/envirohealth). Other recent developments offer opportunities For Children’s Study (Landrigan 2006) evolving platform link approaches. biospecimens collected first 21 years life, study provide resources critical stages. Moreover, extensive questionnaire data, home samples, extant dietary histories participants suggest connections environments. Such prospective cohort allow us collect hazards appropriate preventive measures regulations recognized hazards. play key role endeavors.