trimethyllead and Body-Weight

The literature on the toxicology of lead provides little evidence of the neurotoxicity of organic lead compounds. Toxicant-induced changes in the concentration of glial fibrillary acidic protein (GFAP) in the brain may help clarify at which stage of neurotoxicity astrocytes are affected and whether GFAP may provide an index of toxicity. Male F344 rats (> 42 days old) were exposed to 0 (control), 8 or 16 ppm lead as trimethyl lead (TMPb) in drinking water for up to 14 days. Weight Gain was significantly reduced in both exposed groups. Control rats had the expected brain regional pattern of GFAP concentration with the highest in the hippocampus and cerebellum and lowest in the cerebral cortex. The hippocampus was the region very sensitive to TMPb, with increased GFAP in rats exposed to 8 and 16 ppm TMPb with decreases in GFAP in rats exposed to 8 and 16 ppm TMPb for 14 days. There was a significant time-response in rats exposed to 8 ppm TMPb with decreases in GFAP on day 7 and increases on day 14. A hypothesis concerning this biphasic change in GFAP concentrations is discussed. The results indicate that GFAP may be used to indicate the role of the astrocyte in the neurotoxicity of TMPb. GFAP concentration, as biomarker of TMPb effect, was as sensitive to TMPb as body weight and thus may provide a marker of neurotoxicity.

Topics: Animals; Body Weight; Brain; Dose-Response Relationship, Drug; Drinking; Glial Fibrillary Acidic Protein; Male; Rats; Rats, Inbred F344; Tetraethyl Lead

The dose-related behavioral effects produced by triethyl (TEL) (2.6 to 7.9 mg/kg) and trimethyl lead (TML) (8.8 to 26.2 mg/kg) were assessed 2, 7, 14, 21 and 28 days following injection. TEL, but not TML, produced dose- and time-related decreases in body weight. Both agents decreased vertical and horizontal components of motor activity 2 days postdosing; increased activity was seen consistently in TEL-exposed rats 7 to 21 days after dosing. TML increased fore- and hindlimb strength for up to 28 days postdosing. TEL had no consistent effect on this measure. Both TEL and TML decreased responsiveness to an acoustic stimulus during the first two weeks postdosing. Latency to respond to a thermal stimulus was increased 2 to 14 days after TEL with the peak change occurring from 2 to 7 days. The peak of effect following TML was two weeks postdosing. In general, there was a significant correlation between both TEL and TML-induced changes in blood and brain lead levels and decreased sensitivity to a thermal stimulus. The apparent delayed onset of TML-induced neurobehavioral effects may be related to a longer time to obtain peak blood or brain levels. Histopathological assessment of rats 7 or 28 days after TEL and TML indicated that TEL caused structural abnormalities in the hippocampus and dorsal root ganglion, while TML produced changes primarily in the spinal cord and brain stem.

Topics: Animals; Behavior, Animal; Body Weight; Brain; Dose-Response Relationship, Drug; Male; Motor Activity; Organometallic Compounds; Rats; Rats, Inbred F344; Reaction Time; Reflex, Startle; Sensory Thresholds; Spinal Cord; Tetraethyl Lead