TOXICOKINETICS OF THE CHOLINOMIMETIC COMPOUND BENZYLTRIMETHYLAMMONIUMCHLORIDE IN THE MALE-RAT AND MOUSE

1. Benzyltrimethylammonium chloride (BTMAC)-derived radioactivity was rapidly eliminated from the F344 rat and the B6C3F(1) mouse following p.o. administration of 0.63-63 mg/kg of [ring-U-C-14] BTMAC. Greater t han 90% of the radioactivity was excreted in urine and faeces within 2 4-h post-dosing. 2. BTMAC was poorly to moderately absorbed from the G I tract following p.o. administration. The percent of total dose absor bed did not exceed either 40% in the rat or 15% in the mouse. 3. Absor ption was linear, but limited, over time following dermal administrati on of 63 mg/kg to the rat. Less than 10% of the total dose was absorbe d from the skin within 24 h of BTMAC application. 4. Metabolism of BTM AC was minimal in both the rat and mouse. Toxicity (excessive choliner gic stimulation and mortality) appears to be attributable to the paren t compound. 5. The limited absorption and rapid elimination of BTMAC s hould result in little or no bioaccumulation in tissues following repe ated exposure to low levels of this compound. The results suggest that greater human health risks map be associated with acute high level ex posure rather than chronic low level exposure.