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© 1992 Oxford University Press

research-article

Neuropathologic Findings in Young Male Rats in a Subchronic Oral Toxicity Study Using Triethyl Lead

A. P. YAGMINAS*, P. B. LITTLE{dagger}, C. G. ROUSSEAUX{ddagger}, C. A. FRANKLIN* and D. C. VILLENEUVE*

*Environmental and Occupational Toxicology Division, Environmental Health Directorate, Health and Welfare Canada Ottawa, KJA 0L2, Canada {dagger}Department of Pathologv, Ontario Veterinary College, University of Guelph Guelph, Ontarto NIE 2X7, Canada {ddagger}Department of Veterinary Pathology, Western College of Veterinary Medicine, University of Saskatchewan Saskasoon, Saskatchewan S7N OWO, Canada

Received June 6, 1991; accepted April 23, 1992

This study was undertaken to ascertain the neuropathologic effects of low level exposure of triethyl lead (3EL) to young male rats. Groups of 20 male Sprague—Dawley weanling rats were given 3EL at 0, 0.05, 0.10, 0.20, 0.50, and 1.00 mg/kg body wt for 91 days, 5 days/week by oral gavage. Lead acetate (PbHOAC) was given at 200 mg/kg body wt/day as a positive control. Animals (five or six) were perfused with glutaraldehyde following barbiturate anesthesia at the termination of the experiment. These animals and the remaining members of the group received a thorough gross and microscopic postmortem examination. Sections of the central, peripheral, and autonomic nervous systems were examined and lesions scored. No lesions were noted in the brain, but randomly distributed light microscopic changes of spinal cord Wallerian degeneration were noted to increase in a dose responsive manner (p = 0.48; p < 0.01), with 3EL administration. Ultrastructural examination of selected sections of the lumbosacral nerves, revealed lesions characterized by reduced neurofilaments and neurotubules, and irregular lamellated axoplasmic dense bodies in all animals receiving lead. Organolead was only detected in animals receiving 3EL, but lead cat- ions were detected in all lead-treated animals. The brain lead levels of 1.00 mg/kg/day and 200 mg Pb acetate positive control animals were equivalent. As distinctive ultrastructural lesions were seen in all rats treated with 3EL, we suggest that the no observed adverse effect level (NOAEL) for 3EL be lowered to less than 0.05 mg/kg/day. Further studies using lower concentrations of 3EL are required to determine the ultrastructural NOAEL, to fully describe the distribution of the lesions seen and to define the nature of the dense bodies.


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