Disposition and metabolism of [14C]1,2-dichloropropane following oral and inhalation exposure in Fischer 344 rats

Distribution of 1,2-dichloropropane in blood and other tissues of rats after oral administration

“…In addition, we previously reported that in rats DCP was still detected in the blood 1080 min after the end of a 6-hr inhalation exposure period to 80 or 500 ppm DCP vapor (Take et al, 2014b). Taken together, these data (the present study; Take et al, 2014b;Timchalk et al, 1991) suggest that in rats DCP remains in the blood for a prolonged period of time after administration.…”

“…The peak concentrations of DCP in the blood were similar for both the 62-mg/kg and 125-mg/kg groups; however, in the 62-mg/kg group, DCP remained at its peak concentration in the blood for a limited time while in the 125-mg/kg groups, DCP remained at or near its peak concentration in the blood for several hr. Timchalk et al (1991) reported that in rats [ 14 C]DCP could still be detected in the body 24 and 48 hr after oral administration of 1 or 100 mg/kg body. In addition, we previously reported that in rats DCP was still detected in the blood 1080 min after the end of a 6-hr inhalation exposure period to 80 or 500 ppm DCP vapor (Take et al, 2014b).…”

“…The ratio of the 125-mg/kg group AUC 0-1440 to the 62-mg/kg group AUC 0-1440 is 2.8-fold, slightly higher than the ratio of the administered doses (125-/62-mg/kg group = 2). Timchalk et al (1991) reported the levels of [ 14 C]DCP levels in the rat 24 and 48 hr after oral administration of 1 or 100 mg/kg body weight; however, they did not measure time-course changes in the concentration of DCP in the blood or the T 1/2 or AUC of DCP in the blood after administration (Timchalk et al, 1991). Our study is the first report of the time-course changes, T 1/2 , and AUC of DCP in blood concentration after oral administration and will be valuable in the further development physiologically based pharmacokinetic (PBPK) models of DCP.…”

“…Therefore, understanding the pharmacokinetics of exposure in animal models is one of the fundamental considerations in human risk assessment of exposure to a chemical. Until 2013, only limited information was available about the distribution of DCP in the blood and tissues after inhalation and oral administration (Timchalk et al, 1991). In 2014, we reported the timecourse changes of DCP concentrations in the blood and tissues of rats exposed to 80 or 500 ppm DCP vapor (Take et al, 2014b), concentrations corresponding to the low and high doses used in the two-year inhalation study by Umeda et al (2010).…”

Two Offset Printing Workers with Cholangiocarcinoma

“…It is therefore highly likely that workers exposed to high levels of DCM would develop cholangiocarcinoma. 1,2-DCP is also metabolized by CYP and GST 20) and has a species difference in sensitivity to developing hepatocellular tumors similar to DCM, which suggests that hepatocellular tumors may be related to an intermediate metabolite of 1,2-DCP in the GST pathway. If GST T1-1 plays the largest role in glutathione conjugation of 1,2-DCP, exposed workers would develop cholangiocarcinoma.…”