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BENZENE METABOLISM IN RODENTS AT DOSES RELEVANT TO HUMAN EXPOSURE FROM URBAN AIR
Impact/Purpose:
Human exposure to high levels of benzene is associated with development of leukemia and other blood disorders, but the effects of exposure to low levels of benzene are not well understood. In the1990s, HEI initiated its Air Toxics Research Program to address uncertainties about health effects of ambient levels of benzene and other air toxics derived from mobile and other sources. One of the program’s goals was to develop methods sensitive enough to measure benzene metabolism at low exposure levels. Such sensitivity is important because one or more benzene metabolites are thought to be responsible for benzene’s toxic effects. In addition, understanding benzene metabolism at low exposure levels is critical to benzene risk assessment because the shape of the dose-response curve at low concentrations is not yet resolved.
Description:
Investigators, led by Dr. Kenneth Turteltaub, researched benzene metabolism in rodents over a hundred million–fold dose range. This range encompassed concentrations close to those of human ambient exposure, generally 1 to 10 parts per billion. Turteltaub and his colleague, Chitra Mani, administered radioactive benzene to mice and rats and subsequently analyzed bone marrow, liver, urine, and plasma from these animals. In most experiments, the investigators injected animals intraperitoneally with 14C-labeled benzene, but in some experiments they exposed animals to radioactive benzene via inhalation. After exposure, the investigators coupled high-performance liquid chromatography (HPLC; to separate benzene metabolites) with the novel and sensitive technique accelerator mass spectrometry (to measure 14C) in order to measure low levels of metabolites. Accelerator mass spectrometry was developed by nuclear physicists to measure low levels (10-15 to 10-18 molar) of long-lived isotopes such as 14C.