Assessment of the immunotoxic potential of trichloroethylene and perchloroethylene in rats following inhalation exposure.

The immunotoxic potential of trichloroethylene (TCE) and perchloroethylene (PERC) was assessed after inhalation exposure through the evaluation of the antibody forming cell (AFC) response to sheep red blood cells (SRBC). Female Sprague-Dawley rats were exposed to TCE or PERC vapor at 0, 100, 300, or 1000 ppm for 6 h/day, 5 days/week for 4 weeks (20 exposure days). Additional 0 ppm control groups were included and were dosed with cyclophosphamide via intraperitoneal injection to serve as positive immunosuppressive controls in the SRBC assay. Additional end-points evaluated included liver, kidney, spleen, and thymus weights, hematology, cellular differentials in bronchoalveolar lavage fluid, histopathology of select tissues, and assessment of the phagocytic activity of pulmonary alveolar macrophage (PERC only). Exposure to the high concentration of TCE (1000 ppm) resulted in increases in relative liver and kidney weights and suppression of AFC responses (AFC/spleen and AFC/10(6) spleen cells) by ≈ 70%, while no treatment-related effects were noted at 100 and 300 ppm. Animals exposed to PERC at levels of 300 or 1000 ppm had statistically significant increases in relative liver weights that were accompanied by very slight hypertrophy of the centrilobular hepatocytes. Animals exposed to PERC did not demonstrate a treatment-related effect on the AFC response and no effect was noted on the phagocytic activity of pulmonary alveolar macrophages. The results of these studies indicate that TCE had immunotoxic potential only at high exposure concentrations (1000 ppm), while PERC, at similar exposure concentrations, did not display any evidence of immunotoxicity.

Assessment of behavioral effects of tetrachloroethylene using a set of time-series analyses.

A systematic approach to the analysis of time-series data for spontaneous locomotor activity in the rat was developed to evaluate the behavioral effects of chemical substances. Chronogram, spectral analysis, analysis of the slope of fluctuation, and the cosinor method were used to analyze data obtained by continuously recording spontaneous locomotor activity in the rat. Under synchronized conditions, a circadian period of 24 h was observed and the 1/f fluctuation, in which the power spectral density is inversely proportional to frequency, was confirmed. The 1/f fluctuation was considered to reflect the fractal-like structure of ultradian components of spontaneous locomotor activity. IP administration of 1.0 g/kg body weight of tetrachloroethylene at 0900 h produced a remarkable phase-shift (4.0 +/- 0.9 h) in the activity rhythm and an increase in the slope of fluctuation (0.4 +/- 0.1) in contrast to a relatively smaller decrease in the total amount of spontaneous locomotor activity. These behavioral effects of tetrachloroethylene were dose-dependently lower at lower doses. The present study demonstrated the usefulness of our systematic approach in evaluating the behavioral effects of chemical substances.