Dutcher J S, Medinsky M A, Bond J A, Cheng Y S, Snipes M B, Henderson R F, Birnbaum L S
Fundam Appl Toxicol. 1985 Oct;5(5):997-1005. doi: 10.1016/0272-0590(85)90182-4.
2,3-Dichloropropene (DCP) is an intermediate used in the manufacture of carbamate herbicides and there is potential for human exposure during the manufacturing process. DCP is a known mutagen in bacteria systems and some structural analogs of DCP are carcinogenic. Since little is known about the disposition of DCP in animals after inhalation, studies were conducted in male Fischer-344 rats to determine the effect of vapor concentration on absorption and excretion. Uptake and elimination of 14C was studied in rats after nose-only inhalation of 17, 240, or 1650 nmol of [14C]DCP vapor/liter of air (0.4, 6, or 40 ppm, respectively, at 760 mm and 25 degrees C) for 6 hr. The percentage of inhaled DCP absorbed averaged 38% and was not statistically different at any vapor concentration, although minute volume was lower during exposure to 1650 nmol/liter. Urine, feces, and expired air were collected from rats for 65 hr after exposure. Rats were sacrificed and tissues, carcass, excreta, and expired air were analyzed for 14C. Routes of 14C excretion were independent of vapor concentration, with 50% of the 14C excreted in urine, 13% in feces, approximately 7% as CO2, and less than 1% as DCP in expired air. Rates of 14C excretion were also independent of vapor concentration, with the half-times averaging 9.9 hr (urine), 13.6 hr (feces), and 0.9 hr (14CO2). Sixty hours after inhalation, 29% of the initial body burden of 14C remained in the carcass. Most was associated with the pelt, but some 14C was found in all tissues. Respiratory tract, GI tract, liver, and kidney were tissues with the highest 14C contents. The results indicate that DCP metabolism and excretion rates are relatively constant throughout the vapor concentration range studied. This suggests that results from more detailed pharmacokinetic studies (and possibly toxicity studies) at one DCP concentration may be extrapolated to other concentrations within this range.
2,3 - 二氯丙烯（DCP）是一种用于制造氨基甲酸酯类除草剂的中间体，在制造过程中存在人类接触的可能性。DCP在细菌系统中是一种已知的诱变剂，并且DCP的一些结构类似物具有致癌性。由于对吸入后DCP在动物体内的处置了解甚少，因此在雄性Fischer - 344大鼠中进行了研究，以确定蒸汽浓度对吸收和排泄的影响。在仅经鼻吸入17、240或1650 nmol的[¹⁴C]DCP蒸汽/升空气（在760 mmHg和25℃下分别为0.4、6或40 ppm）6小时后，研究了大鼠体内¹⁴C的摄取和消除情况。吸入的DCP平均吸收百分比为38%，在任何蒸汽浓度下均无统计学差异，尽管在暴露于1650 nmol/升期间分钟通气量较低。暴露后从大鼠收集尿液、粪便和呼出空气65小时。处死大鼠后，对组织、尸体、排泄物和呼出空气进行¹⁴C分析。¹⁴C的排泄途径与蒸汽浓度无关，50%的¹⁴C通过尿液排泄，13%通过粪便排泄，约7%以二氧化碳形式排泄，呼出空气中以DCP形式排泄的不到1%。¹⁴C的排泄速率也与蒸汽浓度无关，半衰期平均为9.9小时（尿液）、13.6小时（粪便）和0.9小时（¹⁴CO₂）。吸入60小时后，初始体内¹⁴C负荷的29%保留在尸体中。大部分与皮毛相关，但在所有组织中都发现了一些¹⁴C。呼吸道、胃肠道、肝脏和肾脏是¹⁴C含量最高的组织。结果表明，在所研究的蒸汽浓度范围内，DCP的代谢和排泄速率相对恒定。这表明在一个DCP浓度下更详细的药代动力学研究（以及可能的毒性研究）结果可以外推到该范围内的其他浓度。
