S Kumagai1, I Matsunaga. 1. Department of Occupational Health, Osaka Prefectural Institute of Public Health, Japan.
Abstract
OBJECTIVES: This study aimed to develop a physiologically based pharmacokinetic model for chlorobenzene and to investigate the effect of variation in exposure to chlorobenzene on the chlorobenzene concentration in blood and the urinary concentration of 4-chlorocatechol. METHODS: A physiologically based pharmacokinetic model was developed and the simulated results of urinary 4-chlorocatechol concentrations were compared with the values found in experiments and field surveys. The area under the chlorobenzene concentration-time curve in blood (CBBauc) was selected as the measure of internal exposure related to the chronic effect of chlorobenzene. The maximum one-hour time weighted average value of chlorobenzene concentration in blood (CBBmax) was chosen as the measure of internal exposure related to the acute effect of chlorobenzene. The total amount of urinary 4-chlorocatechol (TOTCC) and that excreted during the last four hours (CC(4-8)) or two hours (CC(6-8)) of exposure as well as that excreted during two hours on the next morning (CC(22-24)) were used to represent concentrations of urinary metabolites. The effects of variation of the one-hour time weighted averages of airborne chlorobenzene exposure (CBAs) on the internal exposures and the concentrations of urinary metabolites were investigated with the pharmacokinetic model. RESULTS: The comparison of the simulated results with the observed data showed that the pharmacokinetic model can be used to estimate the urinary concentrations of 4-chlorocatechol. The CBBauc and TOTCC were not affected by changes in both the geometric SD (GSD) of CBAs or the variations in CBAs. The CBBmax varied with changes in both the GSD and CBAs. The CC(4-8) and CC(6-8) did not vary with the GSD, but these concentrations were affected by the change in the CBAs. Although there was little effect of the GSD and CBAs on the CC(22-24), this value highly reflected the exposure over the preceding days. CONCLUSION: To protect workers from the chronic effect of chlorobenzene, it may be sufficient to control the daily average exposure. To protect from the acute effect, however, the short term exposure must be controlled as well. The values of CC(4-8) and CC(6-8) were acceptable for estimating daily average exposure, but the CC(22-24) was not.
OBJECTIVES: This study aimed to develop a physiologically based pharmacokinetic model for chlorobenzene and to investigate the effect of variation in exposure to chlorobenzene on the chlorobenzene concentration in blood and the urinary concentration of 4-chlorocatechol. METHODS: A physiologically based pharmacokinetic model was developed and the simulated results of urinary 4-chlorocatechol concentrations were compared with the values found in experiments and field surveys. The area under the chlorobenzene concentration-time curve in blood (CBBauc) was selected as the measure of internal exposure related to the chronic effect of chlorobenzene. The maximum one-hour time weighted average value of chlorobenzene concentration in blood (CBBmax) was chosen as the measure of internal exposure related to the acute effect of chlorobenzene. The total amount of urinary 4-chlorocatechol (TOTCC) and that excreted during the last four hours (CC(4-8)) or two hours (CC(6-8)) of exposure as well as that excreted during two hours on the next morning (CC(22-24)) were used to represent concentrations of urinary metabolites. The effects of variation of the one-hour time weighted averages of airborne chlorobenzene exposure (CBAs) on the internal exposures and the concentrations of urinary metabolites were investigated with the pharmacokinetic model. RESULTS: The comparison of the simulated results with the observed data showed that the pharmacokinetic model can be used to estimate the urinary concentrations of 4-chlorocatechol. The CBBauc and TOTCC were not affected by changes in both the geometric SD (GSD) of CBAs or the variations in CBAs. The CBBmax varied with changes in both the GSD and CBAs. The CC(4-8) and CC(6-8) did not vary with the GSD, but these concentrations were affected by the change in the CBAs. Although there was little effect of the GSD and CBAs on the CC(22-24), this value highly reflected the exposure over the preceding days. CONCLUSION: To protect workers from the chronic effect of chlorobenzene, it may be sufficient to control the daily average exposure. To protect from the acute effect, however, the short term exposure must be controlled as well. The values of CC(4-8) and CC(6-8) were acceptable for estimating daily average exposure, but the CC(22-24) was not.