General remarks on the substances considered.

This eighty-seventh volume of IARC Monographs contains evaluations of inorganic and organic lead compounds. Lead salts and organic lead compounds were considered by the first IARC Monographs Working Groups (Volumes 1 and 2; IARC, 1972, 1973) and they have been reviewed in Volume 23 (IARC, 1980) and updated in Supplement 7 (IARC, 1987). Since 1987, new epidemiological and experimental studies have become available. An IARC Monographs Advisory Group recommended lead compounds as a high and urgent priority for re-evaluation (IARC, 2003). Lead is found at low concentrations in the earth’s crust, predominantly as lead sulfide, but the widespread occurrence of lead in the environment is largely the result of anthropogenic activity. As a result, human exposure to lead is universal, and all humans carry a body burden of lead. Lead has long been of concern for its adverse health effects other than cancer, in particular its neuro-developmental effects on the fetus, infants, and children. These health effects are discussed in this Volume in some detail. Nonetheless, the main focus of this Monograph is on the epidemiological studies and experimental investigations attempting to determine whether exposure to lead is associated with the development of some forms of cancer. In this database, however, there are several limitations that complicate the analysis and evaluation of the carcinogenic potential of lead compounds. Some of these limitations are discussed below. In occupational studies on lead-exposed workers, exposure assessment is complicated by the historical fact that workers with high exposure often were removed from the job, either temporarily or permanently. This may introduce exposure misclassification, making it difficult to discern dose−response relationships using conventional measures such as cumulative exposure or duration of exposure to lead. It should be noted also that the presence of disease can influence the toxicokinetics of lead and, consequently, the reported concentration of lead in blood. Such effects may well affect the findings of clinical studies based on lead measurements made after diagnosis of disease. Although inhalation is an important route of human exposure to lead, the Working Group noted that there was only one long-term inhalation study in experimental animals available for evaluation, and data on inhalation toxicokinetics in humans are very limited. To make inferences about human exposure to lead by inhalation, the Working Group considered information on the toxicokinetics of lead by the inhalation and ingestion routes in experimental animals. Likewise, because of the limited data in humans on mechanistic