摘要：The present study describes the influence of combined exposure to organic solvents on their urinary excretion. Wistar male rats were repeatedly exposed to toluene (TO), xylene (XY) or acetone (AC), individually and simultaneously, or to a mixture of TO and benzene (BE), by intraperitoneal injection (1 injection/week for 12 weeks). Each solvent and mixture was administered in two doses: the high (H) dose was equally to the current occupational exposure limit, the low (L) one was half of the high dose. The rats were divided into 12 groups as follows: (1) 850 (TOH) and (2) 425 (TOL) mg/kg toluene; (3) 1500 (XYH) and (4) 750 (XYL) mg/kg xylene; (5) 1500 (ACH) and (6) 750 (ACL) mg/kg acetone; (7) 1200 (MIH) and (8) 600 (MIL) mg/kg mixture (M) I (30 % TO, 30% XY, 40 % AC); (9) 500 (MIIH) and (10) 250 (MIIL) mg/kg mixture II (85 % TO, 15 % BE); (11) control oil (CO) (0.5 ml oil/100 g body weight) and (12) unexposed control (C). Urine samples were collected for 24 h after the last administration. Major metabolites of TO and XY (hippuric acid and methylhippuric acid, respectively) and urinary AC were measured by spectrophotometric methods. The relationship exposure–excretion was examined by simple regression analysis. The correlation of the solvent exposure doses with the concentrations of the corresponding metabolites was close for TO (r = 0.97; p < 0.001) and XY (r = 0.95; p < 0.05) both in single and in combined administration. Compared with single treatment, simultaneous exposure resulted in higher amounts of excreted hippuric acid (195 %) and methylhippuric acid (200 %) in urine in the immediate post–exposure period. The excretion of hippuric acid in urine from rats co-injected with mixture II was not modified at both doses. These results suggest metabolic interactions between TO, XY and AC that alter initially the excretion of both metabolites and ultimately the biological monitoring of an exposure to a combination of solvents. No apparent interactive effects between TO and BE have been noted.
关键词：organic solvents mixtures, metabolic aspects, experimental study
