Modification of lead distribution by diethyldithiocarbamate

Abstract

Many reports indicate that dithiocarbamates such as diethyldithiocarbamate (DDC), administered in conjunction with exposure to various metals, can elevate the brain levels of such metals at the same time that they promote excretion from other sites. To more clearly define the effects of DDC on lead (Pb) distribution after prolonged exposure to relatively low levels, male Long-Evans rats were provided with drinking water containing 0, 50, or 500 ppm Pb acetate. During the 12-week experimental period, DDC was administered by ip injection twice weekly in a dose of 100 mg/kg. Every 3–4 weeks, urine and blood samples were taken 24 hr before and after a scheduled DDC injection. DDC administration exerted no discernible effect on bone Pb levels and showed only an interaction with Pb dose, but not independent effects on kidney levels. Both liver and brain Pb levels attained much higher levels in the DDC-treated rats than in animals exposed to Pb alone. The sequential measures of Pb in blood and urine and of δ-aminolevulinic acid revealed complex patterns of change over time. One possible explanation, at least for the elevated levels of Pb in brain, is the lipophilic character of the Pb-DDC complex, which facilitates entry into the central nervous system; it may also explain the elevated levels in liver. This property, common to many chelators, suggests their use in model systems to study the neurotoxic properties of metals.