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

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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.

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