Kaleagasìoglu F, Berger M R, Kolar G F
Department of Carcinogenesis and Chemotherapy, German Cancer Research Center, Heidelberg.
Toxicology. 1995 Mar 31;97(1-3):123-31. doi: 10.1016/0300-483x(94)02936-o.
The acute oral toxicity of 3,7-bis-(4-trifluoromethylphenyl)-1,5,3,7-dioxadiazocane (4-TFMPD) was compared with its 3-substituted isomer, 3,7-bis-(3-trifluoromethylphenyl)-1,5,3,7-dioxadiazocane (3-TFMPD) and with N,N'-oxydimethylenebis(2-trifluoromethylaniline) (N,N'-oxy-DM-bis (2-TFMA)). 4-TFMPD, 3-TFMPD, N,N'-oxy-DM-bis (2-TFMA) and their precursors (4-trifluoromethylaniline (4-TFMA), 3-trifluoromethylaniline (3-TFMA) and 2-trifluoromethylaniline (2-TFMA), respectively) were administered intragastrically to male Wistar rats at a dose of 0.12 mmol/kg body weight/day for three consecutive days and the resulting effects on haematological variables were determined. 4-TFMPD induced the highest methaemoglobinemia as compared with 3-TFMPD and N,N'-oxy-DM-bis (2-TFMA). Haemolytic anaemia with Heinz bodies, neutrophilia, lymphocytosis, enlargement of the spleen and enhanced production of granulocytes/macrophages from multipotential bone marrow cells (as determined by CFU-C test) were observed in animals treated with 4-TFMPD and 4-TFMA, whereas no such effects were observed in the other treatment groups. In conclusion, 4-substituted aniline derivatives exert special haematotoxicity on the red blood cells and induce leucocytosis, which differs from the effects of their 2- and 3-substituted congeners.
将3,7-双-(4-三氟甲基苯基)-1,5,3,7-二氧二氮杂环辛烷（4-TFMPD）的急性经口毒性与其3-取代异构体3,7-双-(3-三氟甲基苯基)-1,5,3,7-二氧二氮杂环辛烷（3-TFMPD）以及N,N'-氧二亚甲基双(2-三氟甲基苯胺)（N,N'-氧-DM-双(2-TFMA)）进行了比较。将4-TFMPD、3-TFMPD、N,N'-氧-DM-双(2-TFMA)及其前体（分别为4-三氟甲基苯胺(4-TFMA)、3-三氟甲基苯胺(3-TFMA)和2-三氟甲基苯胺(2-TFMA)）以0.12 mmol/kg体重/天的剂量连续3天经胃内给予雄性Wistar大鼠，并测定其对血液学变量的影响。与3-TFMPD和N,N'-氧-DM-双(2-TFMA)相比，4-TFMPD诱导的高铁血红蛋白血症最高。在用4-TFMPD和4-TFMA处理的动物中观察到了伴有海因茨小体的溶血性贫血、中性粒细胞增多、淋巴细胞增多、脾脏肿大以及多能骨髓细胞产生粒细胞/巨噬细胞增多（通过CFU-C试验测定），而在其他处理组中未观察到此类效应。总之，4-取代苯胺衍生物对红细胞具有特殊的血液毒性并诱导白细胞增多，这与其2-和3-取代的同系物的作用不同。
