Sheets L P, Doherty J D, Law M W, Reiter L W, Crofton K M
Miles Inc., Agriculture Division, Toxicology, Stilwell, Kansas 66085.
Toxicol Appl Pharmacol. 1994 May;126(1):186-90. doi: 10.1006/taap.1994.1106.
Separate groups of weanling and adult rats were exposed to both behaviorally active and lethal doses of deltamethrin to examine age-dependent toxicity of a pyrethroid over a wide dose range. The acoustic startle response (ASR) was selected for comparison at low doses since it is a sensitive, quantifiable biological indicator of pyrethroid effects in rats. Acute mortality was included for comparison at the upper limit of the dose-response. Deltamethrin was administered by gavage as a single dose in corn oil for all tests. Effects on the ASR were comparable in 21- and 72-day-old rats, with a 4-mg/kg dose decreasing ASR amplitude by approximately 50% (ED50) at both ages. By comparison LD50 values in 11-, 21- and 72-day old male rats were 5.1, 11, and 81 mg/kg, respectively. Thus, 11- and 21-day-old male rats were 16 and 7 times, respectively, more sensitive than adults to acute lethality. The concentration of deltamethrin was measured in whole-brain tissue from weanling and adult males treated with ED50 and LD50 doses. The brain concentration of deltamethrin at the ED50 dose of 4 mg/kg was higher in weanling rats than adults. This suggests a possible functional difference, with weanling rats being less susceptible than adults to a low dose. By comparison, there was an equivalent concentration of deltamethrin in brain tissue following an LD50 dose of 12 mg/kg in weanling rats and 80 mg/kg in adults. These results support age-related differences in pharmacokinetics as the basis for the markedly greater sensitivity of young rats to a lethal dose of deltamethrin.
将断奶大鼠和成年大鼠分成不同组,使其接触具有行为活性和致死剂量的溴氰菊酯,以研究拟除虫菊酯在较宽剂量范围内的年龄依赖性毒性。选择低剂量时的听觉惊吓反应(ASR)进行比较,因为它是大鼠体内拟除虫菊酯效应的敏感、可量化的生物学指标。在剂量反应上限处纳入急性死亡率进行比较。所有试验中,溴氰菊酯均以单剂量溶于玉米油中经口灌胃给药。21日龄和72日龄大鼠对ASR的影响相当,4mg/kg剂量在两个年龄段均使ASR幅度降低约50%(半数有效剂量)。相比之下,11日龄、21日龄和72日龄雄性大鼠的半数致死剂量分别为5.1mg/kg、11mg/kg和81mg/kg。因此,11日龄和21日龄雄性大鼠对急性致死性的敏感性分别是成年大鼠的16倍和7倍。测定用半数有效剂量和半数致死剂量处理的断奶雄性大鼠和成年雄性大鼠全脑组织中溴氰菊酯的浓度。4mg/kg半数有效剂量下,断奶大鼠脑内溴氰菊酯浓度高于成年大鼠。这表明可能存在功能差异,断奶大鼠对低剂量的敏感性低于成年大鼠。相比之下,12mg/kg半数致死剂量的断奶大鼠和80mg/kg半数致死剂量的成年大鼠脑组织中溴氰菊酯浓度相当。这些结果支持药代动力学方面与年龄相关的差异是幼鼠对致死剂量溴氰菊酯敏感性明显更高的基础。