Assessment of long-term neurotoxic effects of exposure to mesitylene (1,3,5-trimethylbenzene) based on the analysis of selected behavioral responses.

Trimetylbenzene isomers: pseudocumene, hemimellitene and mesitylene, are major components of numerous commercial solvents and high-grade fuels. In our earlier research on rats we have proved that inhalation exposure to pseudocumene or hemimellitene at concentrations close to the MAC value results in behavioral changes detectable many weeks after cessation of the exposure. The aim of our present study is to determine whether exposure to mesitylene causes effects similar to those observed for pseudocumene and hemimellitene. Male rats were used in the experiment. The animals were exposed in the inhalation chambers to mesitylene vapors at the following concentrations: 0 ppm--group MES0; 25 ppm (125 mg/m3)--group MES25; 100 ppm (500 mg/m3)--group MES100 and 250 ppm (1,250 mg/m3)--group MES250 for 4 weeks (6 h/day, 5 days/week). The following behaviors were tested: 1) ability to find water in a radial maze (14-19 days after the exposure); 2) open field locomotor activity (25 days after the exposure); 3) acquiring the conditioned reaction of active avoidance (35-45 days after the exposure); 4) sensitivity to pain and stress-induced changes of pain sensitivity (50-51 days after the exposure); and 5) acquiring the conditioned reaction of two-way active avoidance (54-60 days after the exposure). Significant between-group differences were noted in passive and active avoidance tests and sensitivity to pain. In the MES25, MES100 and MES250 rats, the persistence of the passive avoidance reaction was shorter, and more trials were required to produce the active avoidance reaction than in controls (group MES0), the MES100 group appeared to be more fearful on the second day of testing on the hot plate. The exposed groups did not differ in the magnitudes of the detected changes (no concentration-effect relationship). These results indicate that inhalation exposure to mesitylene, like that to pseudocumene and hemimellitene, at concentrations close to the current hygiene standard value for trimethylbenzene, may produce long-term functional changes in the rat central nervous system.