As noted in the draft IRIS assessment (section on “Mode of Action for Neurotoxic Effects” [4.6.4]), tetrachloroethylene has much in common with other volatile organic solvents, anesthetics, and alcohols. These shared mechanisms, coupled with similarities in the kinetics of these compounds and the high vulnerability of the developing brain to organic solvents and alcohols, raise concerns about the vulnerability of the developing organisms to tetrachloroethylene. The material on developmental neurotoxicity, while identifying the studies directly pertinent to tetrachloroethylene, omits mention of evidence that might be derived from similarly acting compounds. A separate section might have addressed these issues more thoroughly.
EPA’s selection of neurotoxicity with emphasis on the outcomes of cognitive and visual dysfunction in adults is appropriate as an end point for deriving a point of departure for development of its reference values. However, the committee disagrees with EPA that the study by Altmann et al. (1995) should be the basis for the noncancer risk values. The committee recommends the use of studies by Altmann et al. (1990), Cavalleri et al. (1994) as a baseline for Gobba et al. (1998), and Echeverria et al. (1995). A new animal study by Boyes et al. (2009) also provides a strong basis for a point of departure. Those five studies provide a stronger scientific basis for deriving the RfC and RfD. Despite the importance of the developing nervous system, the literature on potential neurodevelopmental effects is not sufficient to support the derivation of an RfC. This does not mean that developmental neurotoxicity is unlikely. The broader solvent literature raises significant concern about potential developmental neurotoxicity. While the draft IRIS assessment notes that tetrachloroethylene enters the developing brain, it appears to dismiss the potential for developmental neurotoxicity independent of reproductive or maternal toxicity.
Additional research may help to fill gaps in the evidence. For example, studies of developmental neurotoxicity are needed to fill an important gap in the database on tetrachloroethylene. Well-designed epidemiology studies of tetrachloroethylene and neurological end points that characterize both past and current exposure would be helpful. These studies should be done in populations with a range of exposures (such as occupational studies with a wide distribution of exposure and environmental exposures via both air and water).