The neurotoxicity of trimethyltin chloride in hamsters, gerbils and marmosets

Abstract

Trimethyltin chloride (TMT) was given to Syrian hamsters, gerbils and marmosets, and the changes in the brain were studied 1 day to 7 weeks later by light and electron microscopy. Within the marmoset brain, TMT was found to be uniformly distributed, similar to that in the rat. In all three species, signs of poisoning included whole-body tremors and prostration, while death might occur in 3-4 days; in marmosets ataxia, agitation, aggression and occasional fits were also observed. Bilateral symmetrical neuronal necrosis and chromatolysis were seen in the majority, which involved the hippocampus, pyriform cortex, amygdaloid nucleus, neocortex, various brain stem nuclei and in marmosets the retina. The probably lethal dose of TMT in all three species is approximately 3 mg kg-1, while the LD50 for the rat is 12.6 mg kg-1. The lower figure is probably related to lack of binding to haemoglobin in contrast to the binding in the rat. TMT does not bind to human haemoglobin and thus the predicted lethal dose for humans may be about 3 mg kg-1 (15.1 mumol kg-1), while the dose required to produce neuronal damage could well be less.

Biological activity of organotin compounds—An overview

“…The influence of trimethyltin on rodent behavior has received much attention, and was recently summarized by McMillan and Wenger (1985). In monkeys intoxicated with trimethyltin, similar behavioral and neuropathologic alterations were noticed as in rodents (Brown et al, 1984;Reuhl et al, 1985). Also for humans accidentally exposed to trimethyltin a variety of psychomotor changes were reported, including irritability, depression, aggressiveness, headaches, tremors, convulsions, and changes in libido (Fortemps et al, 1978;Ross et al, 1981).…”

A Case of Acute Organotin Poisoning

“…TMT is a by-product of DMTC manufacture 7) . A previous report showed that 8% of TMT was produced as a by-product of DMTC 10) .…”

“…Previous studies have reported that dimethyltin chloride is toxic to the liver and kidneys, whereas trimethyltin chloride damages the central nervous system [2][3][4] . The neurotoxicity of dialkyltin or trialkyltin compounds has been recognized in animal studies, but only a few descriptions of their human toxicity have been reported 1,[5][6][7][8][9][10][11][12][13][14] . Especially, reports of human dimethyltin intoxication are very rare 15) .…”

Neurotoxic Effects of Trimethyltin

“…It is very likely, in the animal body, that some of the chloride ions are substituted by hydroxide ions so that both hydroxides and chlorides are present; since both forms a re soluble in water and in lipids, the rapid passage of trimethyltin through the cellular membranes is possible. The presence of significant amounts of trimethyltin in the nervous system is compatible with the occurrence of pathologic changes; however, there is no evidence that the selective damage of certain neurons is associated with focal concentrations of trimethyltin (Brown et al 1984b). Additional factors, such as the functional state of neurons with hyperactivation of selected systems, may account for their particular vulnerability (Chang and Oyer 1985).…”