NONADDITIVE DEVELOPMENTAL TOXICITY IN MIXTURES OF TRICHLOROETHYLENE, DI(2-ETHYLHEXYL) PHTHALATE, AND HEPTACHLOR IN A 5X5X5 DESIGN
NONADDITIVE DEVELOPMENTAL TOXICITY IN MIXTURES OF TRICHLOROETHYLENE, DI(2-ETHYLHEXYL) PHTHALATE, AND HEPTACHLOR IN A 5X5X5 DESIGN
复制标题
DOI：
10.1006/faat.1995.1125
复制
发表时间：
1995-09-01
期刊：
影响因子：
--
通讯作者：
KAVLOCK, RJ
中科院分区：
文献类型：
--
作者：
NAROTSKY, MG;WELLER, EA;KAVLOCK, RJ
为了鉴定对发育的非加性效应，使用每种药剂的五个剂量组合三种化合物（5 X 5 X 5全因子设计）。在妊娠第6-15天，对Fischer-344大鼠灌胃给予三氯乙烯（TCE）、邻苯二甲酸二（2-乙基己基）酯（DEHP）和七氯（HEPT）的玉米油溶液。TCE的剂量水平为0、10.1、32、101和320 mg/kg/天; DEHP的剂量水平为0、24.7、78、247和780 mg/kg/天; HEPT的剂量水平为0、0.25、0.8、2.5和8 mg/kg/天。允许母鼠分娩，出生后对其幼仔进行称重和检查。母体死亡没有显示出主要影响，但DEHP和HEPT具有协同作用。对于孕6-8天的母体体重增加，观察到所有三种药物的主要影响，以及TCE-DEHP协同作用和DEHP-HEPT拮抗作用。在Gestival第6-20天调整举重体重的母体体重增加显示TCE和HEPT的主要影响，但没有相互作用。所有三种药物对全窝吸收和产前丢失的主要影响均很明显。HEPT的主要作用是出乎意料的，并被解释为反映了HEPT对其他药物的增效作用。对于全窝损失，TCE-HEPT和DEHP-HEPT相互作用是拮抗的，可能是由于“天花板"效应。对于产前丢失，TCE-DEHP相互作用具有协同作用。产后损失显示DEHP和HEPT的主要影响，但没有相互作用。第1天对幼仔体重的分析显示了TCE和DEHP的主要影响以及DEHP-HEPT拮抗作用;第6天，DEHP和HEPT的主要影响、DEHP-HEPT拮抗作用和TCE-DEHP协同作用明显。小眼症和无眼症的发生率显示TCE和DEHP的主要影响，但无相互作用。这种广泛的检查全因子设计阐明了研究和解释混合物毒性的复杂性。这些数据可供进一步分析。(C)1995年毒理学学会
In order to identify nonadditive effects on development, three compounds were combined using five dosages of each agent (a 5 x 5 x 5 full-factorial design). Trichloroethylene (TCE), di(2-ethylhexyl) phthalate (DEHP), and heptachlor (HEPT), in corn oil, were administered by gavage to Fischer-344 rats on Gestation Days 6-15. Dose levels were 0, 10.1, 32, 101, and 320 mg/kg/day for TCE; 0, 24.7, 78, 247, and 780 mg/kg/day for DEHP; and 0, 0.25, 0.8, 2.5, and 8 mg/kg/day for HEPT. The dams were allowed to deliver and their pups were weighed and examined postnatally. Maternal death showed no main effects but DEHP and HEPT were synergistic. For maternal weight gain on Gestational Days 6-8, main effects for all three agents were observed, as well as TCE-DEHP synergism, and DEHP-HEPT antagonism. Maternal weight gain on Gestational Days 6-20 adjusted for lifter weight showed main effects for TCE and HEPT, but no interactions. Main effects for all three agents were evident for full-litter resorptions and prenatal loss. The HEPT main effects were unexpected and were interpreted as reflecting potentiation by HEPT of the other agents. For full-litter loss, the TCE-HEPT and DEHP-HEPT interactions were antagonistic, perhaps due to a ''ceiling'' effect. For prenatal loss, the TCE-DEHP interaction was synergistic. Postnatal loss showed DEHP and HEPT main effects but no interactions. Analysis of pup weights on Day 1 revealed TCE and DEHP main effects and DEHP-HEPT antagonism; on Day 6, DEHP and HEPT main effects, DEHP-HEPT antagonism, and TCE-DEHP synergism were evident. Microphthalmia and anophthalmia incidences revealed TCE and DEHP main effects but no interactions. This extensive examination of a full-factorial design elucidates the complexities of studying and interpreting mixture toxicity. The data are available for further analysis. (C) 1995 Society of Toxicology