toxicity is sufficient or insufficient on the basis of criteria in its risk-assessment guidelines. Some of the specific deficiencies in Section 4.7.2 are described below.
Information analogous to that on page 4-124 of the draft IRIS assessment, which discusses general limitations of the human reproductive-toxicity and developmental-toxicity studies, would be useful. It would provide a context for the descriptions of individual studies and would be helpful in characterizing the animal developmental-toxicity and reproductive-toxicity data available for hazard identification and dose-response evaluation. For example, only two studies of the reproductive toxicity of tetrachloroethylene are described, and many of the developmental-toxicity studies described have limitations. The limitations include use of a single exposure level, insufficient study details, excessive maternal toxicity, and lack of conformity with current EPA and Organisation for Economic Co-operation and Development (OECD) regulatory testing guidelines because of when the studies were conducted.
EPA discusses the evidence on reproductive toxicity and developmental toxicity together. Without a separate discussion of each, it is difficult to identify conflicting data and data gaps and to assess whether there is sufficient evidence of toxicity for each end point according to the criteria in the EPA (1991, 1996) guidelines. The sequence or order in which the studies are described in Section 4.7.2 complicates the issue. The two studies that provide specific information on the reproductive toxicity of tetrachloroethylene, Tinston (1994) and Beliles et al. (1980), are not discussed sequentially. The end-point-specific evidence from the well-conducted Tinston (1994) reproduction study and the Carney et al. (2006) developmental-toxicity study is either not stated or not emphasized by EPA. For example, EPA does not conclude from the Tinston (1994) two-generation reproduction study that tetrachloroethylene had no significant effect on reproductive performance or fertility in rats at up to 1,000 ppm. The results of the Beliles et al. (1980) study, which showed that tetrachloroethylene at 500 ppm had no significant effect on the sperm of rats, are consistent with the adverse effect on fertility in the Tinston study, but the relationship of this finding to the Tinston (1994) study is not discussed. The Summary on page 4-134 does not mention the results of the Carney et al. (2006) developmental study, which showed that tetrachloroethylene at 249 ppm, in the absence of maternal toxicity, can produce developmental toxicity in rats (reduced fetal and placental weights and incomplete ossification of thoracic vertebral centra).