Neurotoxic effects of combined treatment of 2,5-hexanedione and triethyllead chloride.

Abstract

Triethyllead chloride and 2,5-hexanedione are known neurotoxicants that apparently work through separate mechanisms. The effect of combined treatment of triethyllead chloride and 2,5-hexanedione for 6 weeks on Fischer 344 rats was investigated. Ten rats were given 0.7 mg/kg triethyllead chloride in a volume of 2 ml/kg by gavage while another group was given 0.5% 2,5-hexanedione in drinking water and vehicle by gavage (2 ml/kg). A third group was given a combination of the two treatments. A fourth group served as controls and was given vehicle by gavage. 2,5-Hexanedione produced a reversible loss of body weight, decreased grip strength, and decreased horizontal motor activity. Triethyllead chloride alone increased hot-plate latencies. Triethyllead chloride and 2,5-hexanedione treated animals recovered 4 weeks after cessation of treatment. Neither treatment alone produced fatalities. In combination (2,5-hexanedione + triethyllead chloride) decreases in body weight appeared additive and there was a 40% mortality by 6 weeks of dosing. Rats given the combined treatment had significant loss of both grip strength and increased hot-plate latencies. Neurobehavioral deficits and neuropathological changes were greater in the combined treatment with 2,5-HD and TEL than when either chemical was used alone; there was little indication of a synergistic interaction between these two types of neurotoxicants.