Abstract  The developmental toxicity of two trimethylbenzene isomers, mesitylene (1,3,5-trimethylbenzene) and pseudocumene (1,2,4-trimethylbenzene) was studied in Sprague-Dawley rats following inhalation exposure. Pregnant rats were exposed whole body to vapours of mesitylene (0, 100, 300, 600, and 1200 ppm) or pseudocumene (0, 100, 300, 600, and 900 ppm), 6h/day, on gestational days (GD) 6 through 20. Significant decrease in maternal body weight gain and food consumption was observed at concentrations of 300 ppm mesitylene, 600 ppm pseudocumene, or greater. Fetal toxicity, expressed as significant reduction in fetal body weight, occurred at 600 and 1200 ppm mesitylene, and at 600 and 900 ppm pseudocumene. There was no evidence of embryolethal or teratogenic effects following inhalation exposure to either of these chemicals. In summary, the no-observed-adverse-effect-level (NOAEL) for maternal toxicity was 100 ppm for mesitylene and 300 ppm for pseudocumene, and the NOAEL for developmental toxicity was 300 ppm for mesitylene and pseudocumene.

Abstract  Toxic effects of exposure of 1,2,4-trimethylbenzene (pseudocumene) in the condition of sub-chronic inhalation experiment were examined. Rats were exposed to vapours of pseudocumene at concentrations of 123 mg/m3, 492 mg/m3 and 1230 mg/m3, 6 h/day, 5 days/week for 3 months. After 3 months of inhalation exposure animals were necropsied. Blood samples were obtained and selected organs were weighted and prepared for histological examinations. Sub-chronic inhalation exposure to pseudocumene resulted in an overall low degree of systemic toxicity. There were no changes in body weight gain, food consumption and absolute and relative organ weights. Slightly higher activity of sorbitol dehydrogenase was observed in male rats exposed to all concentrations applied. Some disturbances in hematological parameters characterised by decrease in red and increase in white blood cells were observed in male rats exposed to high concentration of 1230 mg/m3. The pulmonary lesions observed in male and female rats were statistically significant at mid and high concentrations of pseudocumene.

Abstract  Neurotoxic effects of trimethylbenzene isomers (pseudocumene, mesitylene and hemimellitene) in male rats were investigated in conditions of acute and subchronic inhalation exposure. Rotarod performance and pain sensitivity behaviour were tested in rats exposed to trimethylbenzenes at concentrations of 250-2,000 ppm immediately after termination of a 4-hour exposure. Exposure to each of trimethylbenzene isomers resulted in concentration-dependent disturbances in rotarod performance, and decrease in pain sensitivity in rats. Pseudocumene, mesitylene and hemimellitene EC50 values for rotarod performance behaviour disturbances were 954, 963, 768 ppm and for decreases in pain sensitivity EC50 were 1,115, 1,212, 848, ppm, respectively. In conditions of subchronic inhalation exposure, pseudocumene and hemimellitene at concentrations of 25, 100 and 250 ppm caused concentration-dependent disturbances in rotarod performance behaviour and decrease in pain sensitivity. Neurotoxic effect of hemimellitene was more pronounced than that of pseudocumene and mesitylene. Two weeks after cessation of inhalation exposure to pseudocumene or hemimellitene no recovery in rotarod performance behaviour was observed.

Abstract  Sensory respiratory irritation effects of trimethylbenzene isomers (TMBs) (hemimellitene, mesitylene and pseudocumene) in male Balb/C mice were investigated in conditions of acute exposure and in male Wistar rats in conditions of repeated 90-day inhalation exposure to pseudocumene. The pseudocumene, mesitylene and hemimellitene concentrations depressing the respiratory rate to 50% (RD50) were 578, 519, 541 ppm, respectively. Inhalation exposure to pseudocumene for 90 days increased the total number of cell macrophages, polymorphonuclear leukocytes and lymphocytes number at all three test concentrations compared with the controls. Total protein lactate dehydrogenase (LDH) and acid phosphatase activity in bronchoalveolar lavage (BAL) were significantly increased in all exposed groups. Based on the effects observed in the respiratory tract, the threshold limit value of at least 10 ppm should be considered for the occupational exposure to trimethylbenzene isomers.

Abstract  Toxic effects of exposure to 1,2,3-trimethylbenzene (hemimellitene) in the condition of subchronic inhalation experiment were examined. Rats were exposed to vapours of hemimellitene at concentrations of 123 mg/m3, 492 mg/m3 and 1230 mg/m3, 6 h/day, 5 days/week for 3 months. After termination of a 3-month inhalation, animals were necropsied. Blood samples were obtained and selected organs were weighed and prepared for histological examinations. Subchronic inhalation exposure to hemimellitene resulted in an overall, low systemic toxicity. There were no changes in body weight gain and food consumption. At a concentration of 1230 mg/m3, the increase in relative liver weight was observed in male rats. It was accompanied by slight increase in sorbitol dehydrogenase activity. The increase in alkaline phosphatase activity was found in females only. Some disturbances in haematological parameters, characterised by the decrease in red blood cells and slight increase in white blood cells, segmented neutrophils and lymphocytes were observed in rats at high exposure concentration of 1230 mg/m3. The pulmonary lesions as well as the increased number of goblet cells and interstitial lung parenchyma infiltration were noted in male and female rats from the highest exposure groups.

Abstract  The zipfile contains the full results (all data, option, session, out, and plot files) of the BMD analyses run on endpoints considered for the derivation of reference values for 1,2,4-TMB and 1,3,5-TMB.