Environmental Chemicals: Evaluating Low-Dose Effects

Around the world, large-scale biomonitoring programs have provided extensive information about human exposure to a large number of environmental chemicals (Barr et al. 2010; Bilau et al. 2008; Churchill et al. 2001; Woodruff et al. 2011). As these programs extend to look at vulnerable populations, including pregnant women, fetuses, and the elderly, our knowledge of the widespread distribution of many of these chemicals—including hundreds that have been classified as endocrine disruptors—continues to climb. However, the mere presence of a chemical in humans is not necessarily cause for concern. What is concerning is the increasing number of epidemiological studies showing associations between the concentration of these chemicals in the general population and adverse health end points (Braun and Hauser 2011; Crain et al. 2008). Although high exposures following accidental or occupational exposures to endocrine disruptors, industrial chemicals, pesticides, and pharmaceuticals have shown striking effects, epidemiological studies suggest that low doses may also be unsafe, even for populations that are not typically considered " vulnerable. " Making connections between the exposome and risk assessment is a difficult but important venture (Paustenbach and Galbraith 2006; Rappaport and Smith 2010). Risk assessments typically examine the effects of high doses of adminis tered chemicals to determine the lowest observed adverse effect levels (LOAELs) and no observed adverse effect levels (NOAELs); reference doses, which are assumed safe for human exposure, are then calculated from these doses using a number of safety factors. Thus, human exposures to thousands of environ mental chemicals fall in the range of non negligible doses that are thought to be safe from a risk assessment perspective. Yet the ever-increasing data from human biomonitoring and epidemiological studies suggests otherwise: Low internal doses of endocrine disruptors found in typical human populations have been linked to obesity (Carwile and Michels 2011), infertility (Meeker and Stapleton 2010), neuro behavioral disorders (Swan et al. 2010), and immune dysfunction (Miyashita et al. 2011), among others. For several decades, environmental health scientists have been dedicated to addressing the " low-dose hypothesis, " which postulates that low doses of chemicals can have effects that would not necessarily be predicted from their effects at high doses. More than 10 years ago, a National Toxicology Program expert panel concluded that there was evidence for low-dose effects for a select number of well-studied endocrine disruptors (Melnick et al. 2002). Now, a diverse group of scientists has reexamined this large body of literature, finding …