ACUTE ORAL TOXICITY IN RATS OF S-(4-TRIFLUOROMETHYLPHENYL)-1,5,3,7-DIOXADIAZOCANE COMPARED WITH S-(3-TRIFLUOROMETHYLPHENYL)-1,5,3,7-DIOXADIAZOCANE AND N,N'-OXYDIMETHYLENEBIS(2-TRIFLUOROMETHYLANILINE)

The acute oral toxicity of 3,7-bis-(4-trifluoromethylphenyl)-1,5,3,7 ( 4-TFMPD) was compared with its 3-substituted isomer, 3,7-bis-(3-triflu oromethylphenyl)-1,5,3,7 (3-TFMPD) and with N,N'oxydimethylenebis(2-tr ifluoromethylaniline) (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-trifluoromethylanili ne (2-TFMA), respectively) were administered intragastrically to male Wistar rats at a dose of 0.12 mmol/kg body weight/day for three consec utive 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 He inz bodies, neutrophilia, lymphocytosis, enlargement of the spleen and enhanced production of granulocytes/macrophages from multipotential b one marrow cells (as determined by CFU-C test) were observed in animal s treated with 4-TFMPD and 4-TFMA, whereas no such effects were observ ed in the other treatment groups. In conclusion, C-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.