• Data from animal studies indicate that TCE can induce liver and lung cancer (mice) and kidney and testicular cancers (rats). Estimates of cancer potencies derived from the animal data differ by over 500-fold (EPA, 2009).
• Potency differences based on animal data are explained in part by the use of different models for low-dose extrapolation, but the current understanding of the biological mechanisms of cancer induction is too limited to allow a selection of the optimal model (EPA, 2009; NRC, 2005).
• The biological reasons for the differences in response between animals and humans are only partially understood, resulting in uncertainty about which studies (animal or human), and which potency estimates (at the lower or higher end of the range) are more reliable and about the nature and extent of possible human risk in populations exposed through the environment (EPA, 2009).
The choices risk assessors make when interpreting the data in light of the uncertainty influence the size of the risk estimate and, in turn, the decision whether or not to regulate TCE and, if so, the nature of the regulatory standards that are based on the risk assessment. For example, if assessors use potency values at the lower end of the range, the assessment may indicate a low likelihood of cancer risk in humans and obviate the need for regulatory action. By contrast, if assessors use potency values at the higher end of the range, the assessment may indicate a high likelihood of cancer risk in humans and be the basis for a more stringent regulatory standard.
be taken into account when considering the duration of exposure for animal studies. It is important to note, however, that despite those limitations enough is known about the similarities and differences between humans and experimental animals to make them relevant to and critical for assessing human health risks (EPA, 2011a).
There is also uncertainty associated with exposure information. One such uncertainty comes from extrapolating from exposures in studies to the exposures experienced by the public. There are instances in which the exposure incurred by the population that is the subject of a risk assessment (that is, the target population) is close to, or even in the same range as, that for which hazard and dose–response data have been collected. For example, studies of exposures to the primary air pollutants ozone, lead, mono-nitrogen oxides, sulfur oxide gases, and particulate matter are often in the same ranges of exposures as occurs with the general population (Dockery et al., 1993; Pope et al., 1995). In many instances, however, the exposure incurred by the target population is only a small fraction—sometimes a