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Dietary ingestion may be a significant pathway of human exposure to many potentially toxic chemicals. The U.S. Environmental Protection Agency-National Human Exposure Laboratory has made the development of methods for measuring personal dietary exposures a high priority for its dietary exposure research program. Of particular interest was the testing of methods that could be applied in the general population as one component of multipathway exposure measurement studies. This paper describes a controlled pilot study that was conducted to evaluate procedures for collecting and processing duplicate diet samples. Nine adult and three child participants volunteered to provide dietary information for 28 days, and duplicate portions of all foods consumed daily for seven consecutive days. Sample collection procedures were evaluated for participant collection and segregation of solid and liquid foods, and for identification and separation of high-fat and low-fat foods. Methods for compositing and homogenizing mixed diet samples were tested. Food records and questionnaires were tested to document the collected food and to evaluate procedures for assessing dietary changes and collection bias. Participant time and monetary needs were evaluated along with the approach for training and providing support to study participants. Participants were able to collect 96% of the meals they consumed, even with 33% of the meals consumed away from home. Food consumed in social settings was the most difficult to collect, and participants were unable or unwilling to collect foods in some social settings. Noncollection of meals and food items increased after the third day of collection. Mixed diet samples were successfully homogenized, with 1%-11% mean relative standard deviations for moisture, fat, protein, and ash analysis in replicate sample aliquots. The laboratory-measured caloric content of collected foods was an average of 12% (range: -24% to 36%) lower than estimates of energy intake using a food diary and 16% lower than estimated energy expenditure values.

The syntheses of several 5-substituted benzimidazoles structurally related to the highly active analgesic 1-(β-diethylaminoethyl)-2-(p-ethoxybenzyl)-5-nitrobenzimidazole are presented.

The isolation and identification of the major in vitro metabolites of chlormadinone acetate are reported. Human, rabbit, and rat liver incubations were employed in the isolation and identification, and male rat liver preparations were used to study the effect of phenobarbital stimulation on the formation of these metabolites. The metabolic pathway was influenced by the microsomal stimulating property of phenobarbital. 2alpha-hydroxychlormadinone was the major metabolite from the incubation of phenobarbital-stimulated rabbit and male rat liver. 17alpha-acetoxy-6-chloro-3beta-hydroxypregna-4,6-diene-20-one was the major metabolite from the incubation of unstimulated human and male rat liver. It was concluded that the 2alpha-hydroxychlormadinone acetate was demostrated only as a consequence of phenobarbital treatment.

In separate experiments, after repeated oral administration of 3,4,4'-trichlorocarbanilide (TCC) and 3-trifluoromethyl-4,4'-dichlorocarbanilide (TFC) to rats, the biliary metabolites of each were isolated and identified. The major TCC biliary metabolite was found to be 2'-hydroxy-TCC. This compound was isolated mainly from the nonconjugated and the glucuronide fractions. Other metabolites present in substantial quantities were 6-hydroxy-TCC and 2',6-dihydroxy-TCC mainly as glucuronides and 3'-hydroxy TCC mainly as the sulfate conjugate. Small amounts of 3',6-dihydroxy-TCC were isolated from each of the fractions. No unchanged TCC was found in the bile. Only traces of other metabolites were found, and no N-hydroxylated products were observed. The major TFC biliary metabolite was the glucuronide conjugate of 2'-hydroxy-TFC. The only other metabolite of TFC was 3'-hydroxy-TFC, which was the predominant metabolite in the sulfate-conjugated fraction.

Tracing the metabolic fate of steroidal antifertility agents is assisted by radioactive labelling. Chlormadinone-4-14C acetate was synthesized, and the reaction sequences are reviewed. The overall yield was moderate (12-16%) but the compound was radiochemically and spectrophotometrically pure. The chemical compounds, structures, and reactions are described in detail.