Subchronic inhalation toxicity of 1,2,3-trimethylbenzene (hemimellitene) in rats.

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.

Sub-chronic inhalation toxicity of 1,2,4-trimethylbenzene (pseudocumene) in rats.

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.

Studies on dermal, ocular and respiratory effects of 4-ethyltoluene in experimental animals.

The toxicity of 4-ethyltoluene to experimental animals was studied after single and repeated exposures. It was found that 4-ethyltoluene can be classified as a very mild skin and eye irritant. Sensory respiratory irritation of 4-ethyltoluene was studied in Balb/C male mice using the plethysmographic method. The concentration at which the respiratory rate decreased to 50% (RD50 value) was determined to be 4216 mg/m3 (2795-5850 mg/m3 for 95% confidence interval). To study repeated-dose inhalation toxicity, male and female outbred Wistar rats were exposed in a dynamic inhalation chamber to 4-ethyltoluene vapours at concentrations of 477 or 2337 mg/m3, 6 h/day, 5 days/week for 4 weeks (20 exposure days). No significant changes were observed in food consumption and body weight gain. Statistically significant, concentration-dependent changes in the number of total cells, as well as of macrophages, polymorphonuclear leucocytes and lymphocytes were found in bronchoalveolar lavage. In the fluid of bronchoalveolar lavage, a significant, concentration-related increase was noted in total protein and mucoproteins and the activity of beta-glucuronidase, gamma-glutamyl transferase, lactate dehydrogenase and acid phosphatase. Histopathology revealed an increased rate of bronchitis and pneumonia and perivascular lymphoid infiltrations in rats exposed to 2337 mg/m3 of 4-ethyltoluene.

Toxic effects of acute inhalation exposure to 1,2,4,5-tetramethylbenzene (durene) in experimental animals.

Neurotoxic and sensory respiratory irritation effects of 1,2,4,5-tetramethylbenzene (durene) in male rats and male Balb/C mice were investigated in the condition of acute inhalation exposure. Rotarod performance and pain sensitivity behaviour were tested in rats exposed to durene at concentrations of 880, 1100 and 1280 mg/m3 immediately after termination of a four-hour exposure. The respiratory rate was measured in mice by the whole body pletysmographic method in a 6-min exposure to various concentrations of durene. Exposure to durene resulted in concentration-dependent decrease in pain sensitivity in rats and depression of respiratory rate in mice. At applied durene concentrations, no statistically significant disturbances in rotarod performance behaviour were observed. The concentration depressing the respiratory rate to 50% (RD50) was 838 mg/m3. As based on RD50 value, MAC of 25 mg/m3 is suggested for durene.

Toxic effects of acute inhalation exposure to 1-methylnaphthalene and 2-methylnaphthalene in experimental animals.

Neurotoxic and sensory respiratory irritation effects of 1-methylnaphthalene and 2-methylnaphthalene in male rats and male Balb/C mice were investigated under conditions of acute inhalation exposure. Rotarod performance and pain sensitivity behaviour were tested in rats exposed to 1-methylnaphthalene at concentrations of 152-407 mg/m3, and 2-methylnaphthalene at concentrations of 229-522 mg/m3 immediately after termination of a four-hour exposure. The respiratory rate was measured in mice by the whole body pletysmographic method in 6 min duration exposure to various concentrations of 1-methylnaphthalene and 2-methylnaphthalene. Exposure to both methylated naphthalene derivatives resulted in concentration-dependent decrease in pain sensitivity in rats and depression of respiratory rate and mice. At the concentrations applied no statistically significant disturbances in rotarod performance behaviour were observed. The concentrations depressing the respiratory rate to 50% (RD50) were 129 mg/m3 and 67 mg/m3, for 1-methylnaphthalene and 2-methylnaphthalene, respectively. As based on RD50 values, the MAC values of 4 mg/m3 for 1-methylnaphthalene, and of 2 mg/m3 for 2-methylnaphthalene are suggested.