Toxicokinetics of the cholinomimetic compound benzyltrimethylammonium chloride in the male rat and mouse.
1. Benzyltrimethylammonium chloride (BTMAC)-derived radioactivity was rapidly eliminated from the F344 rat and the B6C3F1 mouse following p.o. administration of 0.63-63 mg/kg of [ring-U-14C] BTMAC. Greater than 90% of the radioactivity was excreted in urine and faeces within 24-h post-dosing. 2. BTMAC was poorly to moderately absorbed from the GI tract following p.o. administration. The percent of total dose absorbed did not exceed either 40% in the rat or 15% in the mouse. 3. Absorption was linear, but limited, over time following dermal administration of 63 mg/kg to the rat. Less than 10% of the total dose was absorbed from the skin within 24 h of BTMAC application. 4. Metabolism of BTMAC was minimal in both the rat and mouse. Toxicity (excessive cholinergic stimulation and mortality) appears to be attributable to the parent compound. 5. The limited absorption and rapid elimination of BTMAC should result in little or no bioaccumulation in tissues following repeated exposure to low levels of this compound. The results suggest that greater human health risks may be associated with acute high level exposure rather than chronic low level exposure.
Sanders
J M
JM
Chemistry Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Griffin
R J
RJ
Burka
L T
LT
Matthews
H B
HB
D000042:Absorption; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D018678:Cholinergic Agents; D002851:Chromatography, High Pressure Liquid; D007275:Injections, Intravenous; D007408:Intestinal Absorption; D008297:Male; D051379:Mice; D009388:Neostigmine / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D012472:Salivation / Q000187:drug effects; D012867:Skin / Q000378:metabolism
D018678:Cholinergic Agents; D000644:Quaternary Ammonium Compounds; C000168:benzyltrimethylammonium; D009388:Neostigmine; D001285:Atropine