Variations in the neurotoxic potency of trimethyltin.
The organometallic compound, trimethyltin (TMT), is used as a selective denervation tool to validate morphological, biochemical and functional approaches to the detection and characterization of neurotoxicity. Variations in nervous system response TMT have been reported and may complicate the use of this compound as a research tool. We examined the contribution of sample-to-sample differences to variations in TMT-induced neurotoxicity. Seven samples of TMT obtained from three commercial sources were evaluated for neurotoxic potency in the rat. Hippocampus weight, histology and assays of the astrocyte protein, glial fibrillary acidic protein (GFAP), were used as indices of neurotoxicity. A single administration (8.0 mg/kg, IV) of different samples of TMT resulted in markedly different degrees of neurotoxicity as assessed by hippocampus weight and GFAP assays. Subsequent analysis of each sample for trace metal and speciated organotin content revealed that sample-to-sample differences in neurotoxic potency could be attributed to the presence of several impurities. Indeed, in several samples, sodium was present at levels high enough to affect neurotoxic potency simply by diluting the TMT content. A number of samples also showed contamination with the nonneurotoxic organotin, dimethyltin. The data indicate that different sources of TMT produce quantitatively different degrees of neurotoxicity, differences that may be attributed to sample-to-sample variations in TMT content.
O'Callaghan
J P
JP
Health Effects Research Laboratory, U.S. Environmental Protection Agency Research Triangle Park, NC 27711.
Niedzwiecki
D M
DM
Means
J C
JC
D000818:Animals; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D014220:Trialkyltin Compounds / Q000633:toxicity*; D014298:Trimethyltin Compounds / Q000493:pharmacokinetics / Q000633:toxicity*
D005904:Glial Fibrillary Acidic Protein; D014220:Trialkyltin Compounds; D014298:Trimethyltin Compounds; C046488:trimethyltin