[Evaluation of individual exposure to organic solvents using a portable VOC monitor].

Analysis by gas chromatograph after collection of personal samples is the most common method of evaluating individuals' exposures to organic solvents. This method provides us time-weighted averages (TWA) only, and does not measure fluctuating concentrations of organic solvents. A portable VOC monitor is widely used as a rapid screening instrument for volatile organic compounds (VOCs) in houses, schools, etc. The VOC monitor equipped with a photoionization detector can measure real-time concentrations of VOCs. In this study, the author investigated whether the VOC monitor can evaluate individuals' exposures to organic solvents. First, standard organic solvent gases were prepared and the gas concentrations were measured by a passive air sampler and the VOC monitor. Correction factors (CF) were obtained for the response of the isobutylene calibrated VOC monitor to equal concentrations of the organic solvents. Methyl ethyl ketone's CF was 0.5952, toluene's CF was 0.4418, and N,N-dimethylformamide's CF was 0.9017. Then, a mixed standard organic solvents gas was prepared and the gas concentration was measured by both methods. A significant correlation between both methods was obtained (p < 0.001). Subsequently, 37 male workers in a synthetic-leather factory were examined for solvent exposure using both the VOC and a passive sampler, Similar results were obtained by both methods (p < 0.001). Real-time data can be obtained using the VOC monitor and high exposure tasks can be identified. The VOC monitor will be useful for reducing occupational exposure. Since the VOC monitor provides detailed data of individuals' exposures to organic solvents.

In vitro metabolism of tributyltin and triphenyltin by human cytochrome P-450 isoforms.

The metabolic fate of tributyltin and triphenyltin may contribute to the toxicity of these chemicals. We used human hepatic cytochrome P-450 (CYP) systems to confirm the specific CYP(s) involved in the in vitro metabolism of tributyltin and triphenyltin. There were no significant sex differences in the metabolic pattern of tributyltin or triphenyltin, indicating that the CYP(s) responsible for the metabolism of these chemicals in humans is/are not sex-specific form(s). Six major drug-metabolizing isoforms of cDNA-expressed human CYPs and the CYP2C subfamily were tested to determine their metabolic capacities for tributyltin and triphenyltin. CYP2C9, 2C18, 2C19, and 3A4 significantly mediated both dealkylation and dearylation of these triorganotins. Furthermore, the metabolism of tributyltin and triphenyltin was significantly inhibited in vitro by pretreatment with selective inhibitors, azamulin for CYP3A4 and N-3-benzylnirvanol for CYP2C19. Since the CYP2C18 content of hepatic microsomes in humans is relatively low, CYP2C9, 2C19, and 3A4 might be the main isoforms of CYP that are responsible for tributyltin and triphenyltin metabolism in the human liver.

Sex difference in the principal cytochrome P-450 for tributyltin metabolism in rats.

Tributyltin is metabolized by cytochrome P-450 (CYP) system enzymes, and its metabolic fate may contribute to the toxicity of the chemical. In the present study, it is examined whether sex differences in the metabolism of tributyltin exist in rats. In addition, the in vivo and in vitro metabolism of tributyltin was investigated using rat hepatic CYP systems to confirm the principal CYP involved. A significant sex difference in metabolism occurred both in vivo and in vitro, suggesting that one of the CYPs responsible for tributyltin metabolism in rats is male specific or predominant at least. Eight cDNA-expressed rat CYPs, including typical phenobarbital (PB)-inducible forms and members of the CYP2C subfamily, were tested to determine their capability for tributyltin metabolism. Among the enzymes studied, a statistically significant dealkylation of tributyltin was mediated by CYP2C6 and 2C11. Furthermore, the sex difference in metabolism disappeared in vitro after anti-rat CYP2C11 antibody pretreatment because CYP2C11 is a major male-specific form in rats. These results indicate that CYP2C6 is the principal CYP for tributyltin metabolism in female rats, whereas CYP2C11 as well as 2C6 is involved in tributyltin metabolism in male rats, and it is suggested that CYP2C11 is responsible for the significant sex difference in the metabolism of tributyltin observed in rats.

Acute toxic effects of dioctyltin on immune system of rats.

In the present study, dioctyltin chloride (DOTC: 100mg/kg, BW) was orally administered to immature (30-day-old) male rats, and the acute toxic effects were studied. Di- and monooctyltin (its metabolite) accumulations were mainly detected in the liver, and peaked 48h later. A similar pattern was also found in the kidney, but the levels were low or trace amounts. Significantly low thymus and spleen weights were detected in DOTC-treated animals. Increased apoptotic cell numbers in the thymus and spleen were observed in DOTC-treated animals also. Although the expression of 97 genes involved in apoptosis was studied in the thymus, at least 24h after treatment, we could not detect clearly different expressions between DOTC- and vehicle-treated animals. The present results suggest that DOTC was selectively immunotoxic. One of the mechanisms for its immunotoxicity would be via its stimulation of immune cell apoptosis.