Although the nervous system has been identified as the target for alkly-mercurials and -leads, much less information is available concerning the health hazards from environmental exposure to alkyltins. Many signs of alkyltin poisoning in humans can be documented solely as changes in behavior; insomnia, appetite loss, impaired processing of visual information, and memory impairment are prominent clinical signs. The non-human primate provides the best model for human neurotoxicology, both in terms of pharmacokinetics and in terms of complex cognitive functions. Therefore, we propose to compare the neurobehavioral toxicology of the two most toxic alkyltins, triethyltin (TET) and trimethyltin (TMT) in the non-human primate. Behavioral performance on delayed-matching-to-sample will provide evidence of alkyl-tin induced changes in short-term memory; the learning of reversed stimulus-response-reinforcer contingencies will indicate whether or not the impairment is selective for memory. Diurnal cycles in home cage activity will document sleep disturbances. The specificity of these effects will be determined by studies of appetite for food. These behavioral changes will be interpreted with respect to the different pattern of cell damage produced by TET and by TMT. In addition, determining the regional distribution of tin and of histopathology within the monkey brain should provide evidence of critical dose and of neurophysiological mechanisms involved in the toxic response to alkyltins. Preliminary, range-finding studies will be followed by dose-effect and time-effect studies with both acute and subacute oral exposure to TET, TMT or to vehicle. Animals will be female crab-eating Macaques (Cynomolgus).
| Evans, H L; Taylor, J D; Ernst, J et al. (1989) Methods to evaluate the wellbeing of laboratory primates: comparisons of macaques and tamarins. Lab Anim Sci 39:318-23 |
| Bushnell, P J; Evans, H L (1986) Diurnal patterns in homecage behavior of rats after acute exposure to triethyltin. Toxicol Appl Pharmacol 85:346-54 |
| Evans, H L; Bushnell, P J; Pontecorvo, M J et al. (1985) Animal models of environmentally induced memory impairment. Ann N Y Acad Sci 444:513-4 |
| Pontecorvo, M J; Evans, H L (1985) Effects of aniracetam on delayed matching-to-sample performance of monkeys and pigeons. Pharmacol Biochem Behav 22:745-52 |
| Taylor, J D; Evans, H L (1985) Effects of toluene inhalation on behavior and expired carbon dioxide in macaque monkeys. Toxicol Appl Pharmacol 80:487-95 |
