Int. J. Environ. Res. Public Health 2012, 9 2012 Court cases that have addressed challenges to EPA risk assessments confirm this understanding. In Miami-Dade County vs. EPA (discussed above), the 11th Circuit Court of Appeals upheld EPA’s use of conservative risk assessment assumptions [91,92] as a means to address uncertainties. The court found these assumptions to represent a legitimate discretionary decision-making methodology because it was rational for EPA to err on the side of overprotection when faced with data uncertainties ([87], pp. 1069–1070, citing [90,93,94]). In West Virginia vs. EPA (2004), the D.C. Circuit explained that deference is due to an agency’s modeling of complex phenomena, so long as “model assumptions...have a ‘rational relationship’ to the real world” ([93], pp. 866–867). In the American Iron & Steel case (1997), the D.C. Circuit stated that “it is within EPA’s discretion to decide that in the wake of uncertainty, it would be better to give the values a conservative bent rather than err on the other side” ([90], p. 993). The D.C. Circuit found EPA was “reasonable” in using human health uncertainty factors in a risk assessment where the factors were created as a function of the available data ([90], p. 993). In multiple decisions, courts have noted that “[T]he law does not require selection of the single best methodology in any case, but only a study based on consideration of the relevant factors and in the construction of which there has been no clear error of judgment” ([87], p. 1069, internal quotes omitted, citing [95], p. 416). Decision-makers should be mindful that courts often will probe deeply into the science and reason underlying an agency’s decision when a challenger asserts that a choice of methodologies or studies was unreasonable, or that the agency failed to consider a plausible alternative ([96] citing [79], p. 1052 n.7; [72,97–99]). Therefore, if a stakeholder challenges EPA’s use of a cumulative risk assessment methodology when making a decision to set standards “requisite to protect the public health,” the Agency must be able to show that it rationally determined from the available data that it should consider cumulative risks to implement the statutory mandate effectively ([11], p. 378). Such an interpretation of a broad public health mandate arguably would be reasonable in light of compelling scientific evidence of a cumulative adverse health effect ([84] citing [86], p. 378; [87]). One could argue that where new scientific evidence indicates a different approach from the longstanding one would better serve a statutory mandate, Federal agencies should change their standard-setting methodology [49,100]. 4. Conclusions The question of whether EPA may survive a legal challenge to its discretion to make decisions based on data derived from cumulative risk assessment rests on two questions. The first and preeminent question is whether the Agency may interpret or reinterpret its various enabling statutes as providing authority to use this methodology. Assuming EPA has such authority, the second question is whether the cumulative risk assessment methodology and the results derived from that analysis are reasonable, based on the available data. This article suggests that environmental statutes directing EPA to “protect the public health” (or some other similarly broad mandate to protect human health or the environment) likely provide authority for the Agency to use this methodology in various types of decision-making, even if the Agency reinterpreted a statute to provide this authority. In Chevron, the Supreme Court created a two-part framework for reviewing agency interpretations of a statute it implements [49]. At Chevron Step One, a reviewing court examines statutory language to