Susceptibility to lead toxicity.

Adverse effects of lead on human health have been recognized for centuries. Nevertheless , current public health measures require a greater understanding of the pathobiology of chronic low level exposure (1-3). Such considerations are related to the question of what level of lead intake is harmful and why specific clinical manifestations of lead poisoning are encountered under particular circumstances. The recognition of factors, both synergistic and antagonistic, which influence the toxicity of lead is essential for adequate understanding of the effects of environmental lead on human health. The immense body of literature already written about lead contains many clues to and impressions of such factors, both adverse and beneficial, modifying the toxicity of lead. This brief review will discuss a number of such factors. Few of these have as yet been subjected to rigorous experimental confirmation. A consideration of antagonisms and synergisms is based on certain assumptions with regard to the metabolism of lead; that is, the daily intake and excretion of lead as well as the movement of lead between various tissues and effects on cells and subcellular organelles. The principle route of entry of lead into the body is oral. Net absorption of lead by the gastro-intestinal tract is about 5 to 15 per cent; the rest is excreted in the feces. Even inhaled lead particles with an average diameter above 0.5 ,u are cleared by cil-iary action of respiratory epithelial cells and swallowed into the gastro-intestinal tract. The daily intake of lead by adults probably varies from 0.10 mg/day to more than 2 mg but averages between 200 and 500 ,ug per day (4-5). Most information about lead metabolism is related to levels of intake and excretion; we know even less about how lead moves about in the body or how it is handled at the cellular level. It is here that more knowledge is very much needed. Inside the body lead must exist in two forms: a diffusible or mobile form and a non-diffusible or fixed form. Lead must be in a diffusible form in tissues which transport it from one part of the body to another as in red blood cells and plasma, and in organs where lead is transported across cell membranes as in the liver and kidneys. Diffusible lead is sometimes equated with "biologically active" lead but this term may be more appropriately reserved for forms of lead which bind to membranes, enzymes, …