Identification of polynuclear aromatic hydrocarbons in cigarette smoke and their importance as tumorigens.

Fraction F20, which in other studies was the most tumorigenic neutral fraction of cigarette smoke condensate (CSC), was separated by gel filtration chromatography into refined subfractions for identification of the polynuclear aromatic hydrocarbons (PAH) and for bioassay on mouse skin. Several hundred PAH were positively identified. Subfraction F55. containing most of the carcinogenic PAH as well as numerous unidentified components, was almost as tumorigenic to 7,12-dimethylbenze[a]anthracene (DMBA)-pretreated female outbred CD-1 mice as was F20. When F55 was separated into two parts, the first containing unidentified material (F55A) and the second containing the PAH (F55B), neither was significantly tumorigenic. F55B, combined with two other active fractions from the neutral and the acidic portions of CSC, exhibited a synergistic tumorigenic effect on DMBA-pretreated mice. The results supported the concept that the PAH in cigarette smoke must interact with other components in order to exert a tumorigenic effect.

Validated extraction and cleanup procedures for polychlorinated biphenyls and DDE in human body fluids and infant formula.

As part of an epidemiology study, extraction methods and extract cleanup procedures were developed and validated for polychlorinated biphenyls (PCBs) and DDE, an ubiquitous metabolite of DDT, in human milk, blood serum, and infant formula. Studies included quantitative and reproducible recovery of total lipids, and reproducible and reasonably high recoveries of these chlorinated compounds from the human body fluids and infant formula, including levels of environmental health interest. An extensive quality control and assurance program was designed for use with these methods. Some validation work on serum was done using radiolabeled 14C-Aroclor 1254. Dilution assays were developed to permit use of a constant procedure, which should minimize variability in results. Methods are based on selected organic solvent extraction and column chromatographic cleanup techniques and quantitation by electron capture gas chromatography (EC/GC). Using these extensively researched extraction and cleanup methods, the limits of detection for GC measurements were 10.0 and 2.00 ppb for PCBs and DDE, respectively, in milk and 4.00 and 0.80 ppb in serum.

Subchronic feeding study of the mycotoxin fumonisin B1 in B6C3F1 mice and Fischer 344 rats.

Fumonisin B1 (FB1) is a mycotoxin produced by Fusarium moniliforme, a common fungus which occurs naturally on corn, and other Fusarium species. FB1 and other fumonisins are now recognized as having potentially important animal and human health implications. However, few toxicological data are currently available. Male and female B6C3F1 mice and Fischer 344 rats were fed diets containing 0, 1, 3, 9, 27, or 81 ppm FB1 (> or = 98% purity) for 13 weeks. No differences in behavior or appearance, body weight or food consumption between control and FB1-fed groups were found. In mice, hepatopathy and altered serum chemical profiles indicative of hepatotoxicity were found in females fed the 81 ppm diet. No adverse effects were found in female mice fed < or = 27 ppm FB1 or in male mice at any dietary level studied. In rats, nephrosis involving the outer medulla was found in males fed > or = 9 ppm and, to a lesser degree, in females fed 81 ppm FB1, while decreased kidney weight was found in both sexes at dietary levels > or = 9 ppm FB1. Although the liver is a target organ of FB1 in rats, hepatotoxicity was not found in rats fed diets containing up to 81 ppm FB1 for 90 days. Thus, FB1 was toxic to both species following subchronic oral exposure, although significant interspecies differences in the no observed effect levels and organ-specific responses were found.

Human factors in chemical containment laboratory design.

A human factors engineering analysis of a chemical containment laboratory was performed to develop appropriate standards for future laboratory design. In order to perform this evaluation, a state-of-the-art facility was studied in depth. Measurements and observations were made of key operating areas. In addition, technicians were observed and interviewed as they performed various tasks. Compiled data were compared to existing ergonomic standards. The occupational implications of instituting ergonomically developed laboratory design standards are as follows: increased worker health, safety and productivity, improved work quality and reduced stress.