industry consultants. As of June 2008, there are only five studies of anogenital distance in humans, and one researcher has stated "Whether AGD measures in humans relate to clinically important outcomes, however, remains to be determined, as does its utility as a measure of androgen action in epidemiologic studies." Effects on levels of the body's own hormones While the fact that there are chemical differences between endocrine disruptors and endogenous hormones have sometimes been cited as an argument for endocrine disruptors affecting only some (not all) of the traits that are affected by hormones, toxicology research shows that many of the effects of endocrine disruptors target the aspects of hormone effects that make one hormone regulate the production and/or degradation of the body's own hormones. These regulation effects are intertwined so that a hormone that is level affected by another hormone in turn affects the levels of multiple other hormones produced by the body itself, leaving no endogenous hormones or traits affected by them unaffected by endocrine disruptors. Endocrine disruptors have the potential to mimic or antagonize natural hormones, these chemicals can exert their effects by acting through interaction with nuclear receptors, the aryl hydrocarbon receptor or membrane bound receptors. U-shaped dose-response curve Most toxicants, including endocrine disruptors, have been claimed to follow a U-shaped dose-response curve. This means that very low and very high levels have more effects than mid-level exposure to a toxicant. Endocrine disrupting effects have been noted in animals exposed to environmentally relevant levels of some chemicals. For example, a common flame retardant, BDE-47, affects the reproductive system and thyroid gland of female rats in doses of the order of those to which humans are exposed. Low concentrations of endocrine disruptors can also have synergistic effects in amphibians, but it is not clear that this is an effect mediated through the endocrine system. Critics have argued that data suggest that the amounts of chemicals in the environment are too low to cause an effect. A consensus statement by the Learning and Developmental Disabilities Initiative argued that "The very low-dose effects of endocrine disruptors cannot be predicted from high-dose studies, which contradicts the standard 'dose makes the poison' rule of toxicology. Nontraditional dose-response curves are referred to as nonmonotonic dose response curves." The dosage objection could also be overcome if low concentrations of different endocrine disruptors are synergistic. This paper was published in Science in June 1996,