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Adult BALB/c mice were injected IP with trimethyltin . HCl (TMT), and the effects of TMT were studied on gross behavior, lethality, spontaneous motor activity (SMA), and responding under a multiple fixed-ratio 30, fixed-interval 600 sec (mult FR30 FI600) schedule of reinforcement. Following doses of 4, 5, and 6 mg/kg, the cumulative 48-hr lethality was 10% at 4 mg/kg, IP, and 100% at 5 and 6 mg/kg, IP. No deaths were observed during the first 48 hrs following 3 mg/kg TMT. This non-lethal dose produced whole body tremors. The SMA of mice receiving 3 mg/kg was reduced to 70% during the first 24-hr period following TMT and some recovery of total activity was observed during the second 24-hr period. The reduction in SMA was accompanied by a change in the normal circadian cycle of activity. Responding under the mult FR30 FI600 schedule was severely disrupted. Three hours after TMT administration and rate of responding in both components was decreased and the decrease became progressively larger over the next 48 hrs. In addition to the rate of FI600 responding being reduced, the normal pattern of FI responding was altered with an increase in responding observed in the early portions of the FI. These results suggest that the mouse is much more sensitive to the effects of TMT than the rat and may have potential as an animal model in the study of the neurotoxicity of TMT.

The effects of reduced body weight gain on nervous system function of young male Fischer 344 rats were examined. The rats were fed 15% ('mild') or 50% ('severe') less than the controls. Mild and severe dietary restriction resulted in 9% and 38% lower body weight compared to the controls. Mild dietary restriction caused slight changes in flash evoked potentials, auditory brainstem responses, caudal nerve action potentials, and body temperature. Severe dietary restriction increased the magnitude of the effects noted in the mild group, as well as causing a significant decrease in grip strength. Somatosensory evoked responses were not affected by either mild or severe restriction. Diet restricted rats were more excitable while restrained for testing. Thus, dietary restriction has significant effects on numerous behavioral and neurophysiological parameters that should be considered in the interpretation of neurotoxicological data when body weight differences are present.

The effects of trimethyltin (TMT) on the mouse adrenal histology and its relationship with neuropathology occurrence was studied. Young, male CD-1 mice were divided into three groups: group I, injected on 3 consecutive days with 1.0 mg TMT/kg body weight (b.w.); group II, injected on 2 consecutive days with 1.5 mg TMT/kg b.w.; and group III, injected with a single acute dose of 3.0 mg TMT/kg b.w. Control animals were injected with saline solution. The brain and adrenal glands were sampled for light-microscopic examination. Although all animals received the same total amount of TMT, pathological changes in the granule cells of the fascia dentate appeared to be group III greater than group II greater than group I, suggesting that acute exposures produced a more severe damage to the fascia dentate neurons. Likewise, the adrenal weights of the animals were group III greater than group II greater than group I greater than or equal to control. Significant proliferation and enlargement of the eosinophilic or the "X zone" were observed in the TMT-treated, particularly groups II and III, animals. The expansion of the eosinophilic cell layer (X zone) was accomplished at the expense of the cortical fasciculata cells. Transformation of fasciculata cells into eosinophilic cells could also be demonstrated. As the eosinophilic cells are known to be active in corticosterone production as seen in stress situations, the proliferation of these cells may reflect a feedback response to the hippocampal hyperexcitation.

The covalent binding of chemical carcinogens and mutagens to hemoglobin has been proposed as a dose monitor for environmental exposure. The binding of chloroform to hemoglobin in rats was demonstrated to result from the formation of addition adducts to amino acids in the globin. The altered amino acids were isolated with an amino acid analyzer employing ion exchange chromatography. The covalent binding of orally-administered [14C]chloroform to rat hemoglobin reached a peak within 10 h. Afterwards, the amount of chloroform bound decreased slowly with half remaining at 7 weeks. The extent of chloroform binding was linearly dependent upon dose between 0.1 and 100 mumol/kg. Above 100 mumol/kg chloroform the binding to hemoglobin increased at a reduced rate. The extent of [14C]chloroform binding resulting from either 10 daily doses of 0.1 mumol/kg or a single 1.0 mumol/kg was similar. The binding to hemoglobin in three strains of mice and rats varied from 85 +/- 7 mumol/g Hb for Swiss (CFN) mice to 152 +/- 14 for Fisher-344 rats. We have demonstrated that the binding of chloroform to hemoglobin appears to have the following attributes of a dose monitor: (1) easily accessible from laboratory animals (and humans); (2) dose dependent; (3) stability, so that exposure can be determined weeks after it has ceased; (4) integration of low exposures which individually would be undetectable.

The effects of corn oil on rat dorsal root ganglia (DRG) were examined by both light and electron microscopy. Rats were fed corn oil via intubation 5 days per week for 7 weeks. No apparent morphological lesion was observed in the DRG by means of light microscopic examination. However, various cytological changes were revealed by electron microscopy. The most prominent change was the extensive and severe edematous condition in the interstitial space. After 7 weeks of treatment, the interstitial space between neurons and nerve fibers was distended by proteinaceous edematous fluid and collagen fibers. Distention of the intercellular space between the ganglion neurons and their surrounding satellite cell sheaths also occurred. Proliferation of the supporting cells, especially the satellite cells and Schwann cells, producing long and complex networks of cellular processes in the distended interstitial space was also evident. It is believed that chronic ingestion of corn oil by rats has an adverse effect on the endothelial system leading to an increased fluid permeability and edematous condition.

Serum antibody concentrations against influenza A-equi-1 virus and A-equi-2 virus were measured in a group of 18 foals from birth to 4 months of age. More than 50% of the foals were seronegative to A-equi-1 virus infection by 4 weeks of age, with titers of less than or equal to 1:16. For A-equi-2 virus, more than 50% of the foals were seronegative by 2 weeks of age, with titers of less than or equal to 1:8. Passively derived antibodies against influenza A-equi-1 virus and A-equi-2 virus in foals obtained from recently vaccinated mares and from mares not vaccinated within 6 months before foaling were low in titer. The duration of passively derived antibodies was also short-lived.