Lilly P D, Simmons J E, Pegram R A
Department of Environmental Sciences and Engineering, University of North Carolina-Chapel Hill.
Fundam Appl Toxicol. 1994 Jul;23(1):132-40. doi: 10.1006/faat.1994.1089.
Bromodichloromethane (BDCM) is a disinfection by-product of drinking water chlorination and is the second most common trihalomethane (THM) in finished drinking water. THMs have generally been administered to experimental animals in corn oil, rather than drinking water, which can influence the site and magnitude of toxicity. To examine the effects of gavage vehicle on the acute renal and hepatic toxicity of orally administered BDCM, 95-day-old male F344 rats were given single doses of 0, 200, or 400 mg BDCM/kg in corn oil or an aqueous 10% Emulphor solution. Activities of serum hepatoxicity indicators were significantly greater 48 hr after administration of 400 mg BDCM/kg in corn oil compared to the aqueous vehicle, but delivery of the low dose in either dosing vehicle had little effect on serum enzymes. In contrast, significant elevations in urinary renal toxicity indicators were noted at 200 and 400 mg BDCM/kg in both vehicles after 24 hr, indicating that the kidney is more sensitive to low doses of BDCM than the liver. Significantly greater increases were observed in urinary indicators after delivery of 200 mg BDCM/kg in 10% Emulphor compared to corn oil. However, administration of the high dose in corn oil resulted in greater nephrotoxicity than in the aqueous vehicle. Significant interactions between vehicle of administration and BDCM dose observed for both urinary and serum parameters further indicate that vehicle differences noted in BDCM acute toxicity are dose dependent. This observation may be due to pharmacokinetic differences in gastrointestinal rates of absorption of BDCM from corn oil as compared to an aqueous solution.
溴二氯甲烷（BDCM）是饮用水氯化消毒的副产物，是成品饮用水中第二常见的三卤甲烷（THM）。通常给实验动物经玉米油而非饮用水给予三卤甲烷，这可能会影响毒性的部位和程度。为了研究灌胃溶媒对口服BDCM急性肾毒性和肝毒性的影响，给95日龄雄性F344大鼠单次经玉米油或10%乳化剂水溶液给予0、200或400mg BDCM/kg。与水性溶媒相比，经玉米油给予400mg BDCM/kg后48小时，血清肝毒性指标活性显著更高，但两种给药溶媒中低剂量给药对血清酶影响不大。相比之下，两种溶媒中200和400mg BDCM/kg给药24小时后，尿肾毒性指标均显著升高，表明肾脏对低剂量BDCM比肝脏更敏感。与玉米油相比，经10%乳化剂给予200mg BDCM/kg后，尿指标升高更显著。然而，经玉米油给予高剂量导致的肾毒性比水性溶媒更大。对于尿和血清参数，观察到给药溶媒与BDCM剂量之间存在显著相互作用，这进一步表明BDCM急性毒性中溶媒差异是剂量依赖性的。这一观察结果可能是由于与水溶液相比，BDCM从玉米油中胃肠道吸收速率的药代动力学差异所致。
