RESUMEN
Trichloroethylene (TRI) and tetrachloroethylene (TETRA) are solvents that have been widely used in a variety of industries, and both are widespread environmental contaminants. In order to provide a better basis for understanding their toxicokinetics at environmental exposures, seven human volunteers were exposed by inhalation to 1 ppm of TRI or TETRA for 6 h, with biological samples collected for analysis during exposure and up to 6-days postexposure. Concentrations of TRI, TETRA, free trichloroethanol (TCOH), total TCOH (free TCOH plus glucuronidated TCOH), and trichloroacetic acid (TCA) were determined in blood and urine; TRI and TETRA concentrations were measured in alveolar breath. Toxicokinetic time courses and empirical analyses of classical toxicokinetic parameters were compared with those reported in previous human volunteer studies, most of which involved exposures that were at least 10-fold higher. Qualitatively, TRI and TETRA toxicokinetics were consistent with previous human studies. Quantitatively, alveolar retention and clearance by exhalation were similar to those found previously but blood and urine data suggest a number of possible toxicokinetic differences. For TRI, data from the current study support lower apparent blood-air partition coefficients, greater apparent metabolic clearance, less TCA production, and greater glucuronidation of TCOH as compared to previous studies. For TETRA, the current data suggest TCA formation that is similar or slightly lower than that of previous studies. Variability and uncertainty in empirical estimates of total TETRA metabolism are substantial, with confidence intervals among different studies substantially overlapping. Relative contributions to observed differences from concentration-dependent toxicokinetics and interindividual and interoccasion variability remain to be determined.
Asunto(s)
Contaminantes Atmosféricos/farmacocinética , Exposición por Inhalación , Solventes/farmacocinética , Tetracloroetileno/farmacocinética , Tricloroetileno/farmacocinética , Contaminantes Atmosféricos/sangre , Contaminantes Atmosféricos/toxicidad , Contaminantes Atmosféricos/orina , Análisis de Varianza , Área Bajo la Curva , Biotransformación , Pruebas Respiratorias , Humanos , Masculino , Tasa de Depuración Metabólica , Modelos Biológicos , Alveolos Pulmonares/metabolismo , Valores de Referencia , Solventes/toxicidad , Tetracloroetileno/sangre , Tetracloroetileno/toxicidad , Tetracloroetileno/orina , Tricloroetileno/sangre , Tricloroetileno/toxicidad , Tricloroetileno/orinaRESUMEN
Percutaneous absorption of m-xylene (XYL) was determined in volunteers exposed to 29.4 microg cm(-3) XYL vapour on the forearm and hand for 20, 45, 120 and 180 min. The internal exposure was assessed by measuring the concentration of XYL in exhaled air. The systemic kinetics were determined using a reference exposure by inhalation. The dermal permeation rate and the cumulative absorption of XYL as a function of time were calculated using mathematical deconvolution. From these relationships, the average flux into the skin throughout the exposure (J(skin, average)) and the maximal flux into the blood (J(blood, max)) were derived. Both fluxes were dependent on the duration of exposure, approaching each other at longer exposure durations. The values of J(skin, average), adjusted to a concentration of 1 microg cm(-3), were 0.091 microg cm(-2) h(-1) during 20-min exposure falling to 0.072, 0.066 and 0.061 microg cm(-2) h(-1) for 45, 120 and 180 min, respectively. The values of J(blood, max) showed an opposite trend, gradually increasing from 0.034 microg cm(-2) h(-1) at an exposure duration of 20 min to 0.042, 0.059 and 0.063 microg cm(-2) h(-1) for 45, 120 and 180 min of exposure durations, respectively.