The systemic plasma pharmacokinetics of genistein were determined in rats to evaluate the absolute oral bioavailability and make comparison with similar data in the literature derived from humans subjects. The plasma concentrations of genistein, genistein glucuronide and carbon-14 were determined by LC-MS/MS and liquid scintillation counting following oral and intravenous dosing with [14C]genistein (4 mg kg(-1) body weight). The absorption of total radioactivity from the gut, (parent compound and metabolites), was 56 and 111% in male and female rats, respectively. In contrast, the absolute oral bioavailability of genistein in male and female rats was 7 and 15%. There was a significant (P<0.001) difference between Cmax of genistein after intravenous (6921 and 4392 ng/ml) and oral (21 and 22 ng/ml) dosing in male and female rats, respectively. After oral administration, the concentration profile of genistein glucuronide in plasma greatly exceeded that of parent compound during the absorption/distribution phase suggesting extensive first pass metabolism, and provided evidence of entero-hepatic circulation. Selective plasma analysis by LC-MS/MS, without prior enzymatic hydrolysis, enabled ready discrimination between parent and conjugated metabolites and prevented gross overestimation of genistein bioavailability. Pharmacokinetic parameters Cmax, Tmax and AUC were similar to those reported in humans, which supports the use of the rat model for genistein toxicity studies.

The faecal concentration of substances responding to the chemical test for N-nitroso compounds (apparent total N-nitroso compounds, ATNC) was investigated in human subjects consuming their normal free-choice diet. Concentrations ranged from 40 to 590 micrograms (N-NO)/kg faeces. To ascertain the likely relative contributions of endogenous ATNC formation and preformed, dietary ATNC, the subjects consumed a diet low in nitrate and ATNC for 8 days. At the end of this period, ATNC had decreased substantially with concentrations ranging from below the 40 micrograms (N-NO)/kg detection limit up to 143 micrograms (N-NO)/kg, mean 82 micrograms (N-NO)/kg. On supplementing this diet with 300 mg nitrate/day, faecal ATNC levels increased markedly. On the third day of this regime, values were in the range 73-714 micrograms (N-NO)/kg with a mean of 307 micrograms (N-NO)/kg. The results, together with the known limited occurrence of ATNC in the majority of foodstuffs so far tested, generally non-detectable or less than 100 micrograms (N-NO)/kg, suggest that endogenous formation via species derived from dietary nitrate is likely to be an important source of ATNC in human faeces.

No abstract

An analytical procedure has been developed for the determination of trace amounts of ethyl carbamate in fermented foodstuffs and alcoholic beverages. Concentrations were generally below the 1-5 micrograms/kg detection limit in bread, cheese, yoghurt, beer, gin and vodka. Higher concentrations were found in the other alcoholic beverages examined, which included whisky, fruit brandy, liqueur, wine, sherry and port.

Over 170 retail samples of beer have been analysed for N-nitrosodimethylamine (NDMA), apparent total N-nitroso compounds (ATNC) and nitrate. Levels of NDMA ranged from below 0.1 up to 1.2 micrograms/kg with a mean of 0.2 micrograms/kg. ATNC was detected in 42% of the samples in concentrations of up to 569 micrograms (N-NO)/kg. The levels of nitrate ranged from less than 0.2 up to 143 mg/kg with a mean of 16.8 mg/kg. There was no correlation between the amounts of NDMA and ATNC found in the retail beers. Samples taken during the course of fermentation showed that NDMA was unaffected by the bacterial reduction of nitrate which causes ATNC formation. HPLC studies using a photolysis/chemiluminescence detector revealed that the ATNC in beer are highly polar species of as yet unknown identity.

A rapid strong anion exchange HPLC/UV procedure has been developed for the determination of nitrate and nitrite in a wide variety of cured meats. The accuracy of this technique has been confirmed by the good agreement achieved with the existing British Standard colorimetric method. The applicability and repeatability of the procedure has been established in a survey of over 200 samples. The agreement between duplicate determinations and their respective means averaged +/- 3.4% for nitrite and +/- 4.3% for nitrate as defined by the term [(a - b)/(a + b)] X 100% where a and b are the repeat determination values.

Twenty-five smoked and unsmoked fried bacon samples have been analysed by a group selective procedure to measure the concentration of apparent total N-nitroso compounds (ATNC). The levels of a range of individual N-nitroso compounds, including simple volatile N-nitrosamines, N-nitrosothiazolidines, N-nitrosamino acids and N-nitrosothiazolidine carboxylic acids have also been examined. Concentrations of ATNC varied from 430 to 6800 micrograms(N-NO)/kg with a mean of 2700 micrograms(N-NO)/kg. Protein-bound N-nitrosoproline was the most abundant compound detected in unsmoked bacon, mean 260 micrograms/kg, and on average accounted for 4% of the ATNC concentration. For smoked bacon, bound N-nitrosoproline was detected in levels of up to 890 micrograms/kg and contributed 5% to the ATNC total. The most abundant compound present in smoked bacon was N-nitrosothiazolidine-4-carboxylic acid, mean 660 micrograms/kg, and this accounted for 6% of the ATNC. N-Nitrosothiazolidine, mean 340 micrograms/kg, and 2-(hydroxymethyl)-3-nitrosothiazolidine-4-carboxylic acid, mean 180 micrograms/kg, were the next most prominent compounds detected in smoked bacon. The combined sum of all the individual N-nitroso compounds measured accounted for, on average, 16% of the total ATNC. The identities of the N-nitroso compounds comprising the majority of the ATNC in bacon remain unknown.

The apparent total N-nitroso content of foods can be measured by a procedure based on chemical denitrosation and chemiluminescent detection of the eliminated nitric oxide. Procedures have been established which substantially reduce the 'apparatus blank' response to the denitrosating agent and allow total nitroso contents down to 10 micrograms (N-NO)/kg to be measured reproducibly on a 1-g sample. Typically, duplicate analyses of samples containing 10-1000 micrograms (N-NO)/kg differ by less than 15% of their mean. Potentially the method can be subject to some interference from compounds other than N-nitroso compounds, but at least in some commodities these interfering compounds do not exist in measurable amounts.