Silkworth J B, Cutler D S, Antrim L, Houston D, Tumasonis C, Kaminsky L S
Wadsworth Center for Laboratories and Research, New York State Department of Health, Albany 12201-0509.
Fundam Appl Toxicol. 1989 Jul;13(1):1-15. doi: 10.1016/0272-0590(89)90302-3.
The organic phase of a leachate (OPL) from the Love Canal chemical dump site contains more than 100 organic compounds including 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD). The teratogenic potential of OPL was determined in two inbred and one hybrid mouse strain which differ in their sensitivity to aromatic hydrocarbon (Ah) receptor-mediated toxicity. OPL was orally administered in corn oil on Days 6-15 of gestation to C57BL/6J mice (Ahb/Ahb) at doses of 0, 0.1, 0.3, 0.5, and 0.7 g kg-1 day-1 and to DBA/2J (Ahd/Ahd) females, which were mated with either DBA/2J or C57BL/6J males, at 0, 0.5, 1, and 2.0 g kg-1 day-1. In C57BL/6J mice, which express a high-affinity Ah receptor that avidly binds TCDD, the ED50's of OPL for cleft palate and hydronephrosis were 0.44 and 0.11 g OPL kg-1 day-1, respectively. Maternal mortality was 5% at the highest dose. In DBA/2J fetuses, which express a low-affinity receptor, neither treatment-related cleft palate nor hydronephrosis was induced by dose levels that caused 36% maternal mortality. In hybrid D2B6F1 fetuses, the incidence of cleft palate reached only 8% at 2 g OPL kg-1 day-1 but the ED50 for hydronephrosis was 0.76 g OPL kg-1 day-1. TCDD was similarly administered to pregnant C57BL/6J mice at 0, 0.5, 1, 2, and 4 micrograms kg-1 day-1 and to DBA/2J mice at 0, 0.5, 2, 4, and 8 micrograms kg-1 day-1. In C57BL/6J fetuses, the ED50's for cleft palate and hydronephrosis were 4.6 and 0.73 microgram TCDD kg-1 day-1, respectively. In DBA/2J fetuses the ED50's for cleft palate and hydronephrosis were 15.0 and 6.4 micrograms TCDD kg-1 day-1, respectively. Both the OPL and TCDD caused maternal hepatomegaly and thymic atrophy in all strains, but increased only C57BL/6J fetal weights. OPL decreased the number of fetuses per C57BL/6J dam at the two highest doses but there were no other reproductive effects in any of the groups. It was concluded that the OPL is teratogenic and that hydronephrosis is a sensitive measure of TCDD toxicity in a complex organic mixture. Based on the ED50's of OPL- and TCDD-induced cleft palate and hydronephrosis in the C57BL/6J strain, the OPL had TCDD equivalence of 6.6 and 10.5 ppm, respectively. These values compare closely with the chemical analysis of 3 ppm.(ABSTRACT TRUNCATED AT 400 WORDS)
拉夫运河化学垃圾场渗滤液的有机相（OPL）含有100多种有机化合物，包括2,3,7,8-四氯二苯并对二恶英（TCDD）。在三种小鼠品系（两种近交系和一种杂交系）中测定了OPL的致畸潜力，这三种品系对芳烃（Ah）受体介导的毒性敏感性不同。在妊娠第6至15天，将OPL溶于玉米油中，以0、0.1、0.3、0.5和0.7 g kg⁻¹ day⁻¹的剂量口服给予C57BL/6J小鼠（Ahb/Ahb），以0、0.5、1和2.0 g kg⁻¹ day⁻¹的剂量口服给予DBA/2J（Ahd/Ahd）雌性小鼠，这些雌性小鼠与DBA/2J或C57BL/6J雄性小鼠交配。在表达高亲和力Ah受体且能 avidly结合TCDD的C57BL/6J小鼠中，OPL导致腭裂和肾积水的半数有效剂量（ED50）分别为0.44和0.11 g OPL kg⁻¹ day⁻¹。最高剂量时母体死亡率为5%。在表达低亲和力受体的DBA/2J胎儿中，导致36%母体死亡率的剂量水平未诱发与治疗相关的腭裂或肾积水。在杂交D2B6F1胎儿中，2 g OPL kg⁻¹ day⁻¹时腭裂发生率仅达8%，但肾积水的ED50为0.76 g OPL kg⁻¹ day⁻¹。以0、0.5、1、2和4微克 kg⁻¹ day⁻¹的剂量将TCDD同样给予怀孕的C57BL/6J小鼠，以0、0.5、2、4和8微克 kg⁻¹ day⁻¹的剂量给予DBA/2J小鼠。在C57BL/6J胎儿中，腭裂和肾积水的ED50分别为4.6和0.73微克TCDD kg⁻¹ day⁻¹。在DBA/2J胎儿中，腭裂和肾积水的ED50分别为15.0和6.4微克TCDD kg⁻¹ day⁻¹。OPL和TCDD在所有品系中均导致母体肝脏肿大和胸腺萎缩，但仅增加了C57BL/6J胎儿体重。最高的两个剂量下，OPL减少了每只C57BL/6J母鼠的胎儿数量，但任何组中均无其他生殖方面的影响。得出的结论是，OPL具有致畸性，肾积水是复杂有机混合物中TCDD毒性的敏感指标。根据C57BL/6J品系中OPL和TCDD诱发腭裂和肾积水的ED50，OPL的TCDD当量分别为6.6和10.5 ppm。这些值与化学分析的3 ppm非常接近。（摘要截短于400字）
