Review of the Environmental Protection Agency's Draft IRIS Assessment of Tetrachloroethylene http://www.nap.edu/catalog/12863.html
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Review of the EPA’s Draft IRIS Assessment of Tetrachloroethylene
LOAEL to NOAEL, from animal to humans, for human variation, and for database deficiencies; the total uncertainty factor was 3,000.” That justification is not clear. The reason for modifying the uncertainty factor may be that it is EPA’s policy to limit the overall uncertainty to 3,000 in deriving RfCs (EPA 2002). If that is the reason, it should be stated explicitly. If not, better justification should be provided. The committee believes that an uncertainty factor of 3 should have been considered for animal studies like that of Mattsson et al. (1998) in which exposure occurred for 6 hours/day 4 days/week for 13 weeks. If that exposure regimen is treated in the same manner as acute exposure by applying a higher factor, doing so should be justified. Some discussion of the issue would improve the draft IRIS assessment. Database Deficiencies In the derivation of RfCs on the basis of neurotoxicity, EPA used a factor of 3 for database deficiencies because of the inadequacy of the experimental literature designed to characterize hazard and dose-response. Key deficiencies identified were inadequate data to address childhood or other life-stage susceptibility, a paucity of animal studies (especially studies of developing animals and of chronic, low-level exposures) designed to investigate neurotoxicity or to define and characterize dose-response relationships, and inadequate database on cognitive testing. It was unclear whether a factor of 3 was adequate to address these uncertainties because there was some overlap with the factor of 10 applied for human variation, which also addressed developmental concerns. The committee recommends that EPA revisit and defend more clearly its decision to apply a factor of 3 for database deficiencies in light of new data and the committee's findings in Chapter 3. New studies include, for example, recent papers from researchers in EPA's National Health and Environmental Effects Research Laboratory provide excellent data from well-designed studies using controlled, acute exposures that link deficits in visual function and signal detection with atmospheric tetrachlorethylene concentrations and instantaneous concentrations in the brain. This includes papers by Oshiro et al. (2008) and Boyes et al. (2009) investigating function and by Shafer et al. (2005) on mechanisms, which is described in the IRIS document but not fully integrated. These studies link neural or behavioral effects to actual brain concentrations of tetrachloroethylene or to their estimated concentration using PBPK modeling. Thus, the animal literature on controlled acute exposure is now stronger. Notable gaps in the animal literature still include the paucity of studies of developmental or chronic exposures. Another consideration is that the committee found the human study of exposed children (Schreiber et al. 2002) to be methodologically flawed. The committee judges these to be serious gaps in the database, which suggests that a factor of 3 may be inadequate to account for database deficiencies.
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