New PBPK model applied to old occupational exposure to benzene

An intensive program of benzene monitoring using new techniques was undertaken in Western Europe in the late 1960s and early 1970s. Significant exposure was found in the transport of benzene and gasoline, particularly during the loading of barges, and during the loading and operation of sea-going vessels. The ceiling threshold limit value of 25 ppm recommended at that time generated problems in assessing exposure, so alternative criteria were proposed. During that period some shore-based exposures were reported, and their significance was discussed in several articles. The information gained at that time is reexamined by physiologically based pharmacokinetic (PBPK) modeling and is used to help validate an improved PBPK model, which is described and tested on results from experimental exposure in a companion article. The old field data, comprising five specific studies, confirm the relevance of modeling to assessment of occupational exposure, and demonstrate its value for interpretation of field data, which is seldom as complete, systematic, or accurate as that obtained in experimental work. The model suggests that metabolism of benzene in humans may not be restricted to the liver. Sites and processes of metabolism merit further investigation.