Fipronil and fipronil sulfone in chicken: From in vitro experiments to in vivo PBK model predictions.

In 2017 a large-scale fipronil contamination in eggs occurred in several European countries. Fipronil and its metabolites have the potential to be transferred into the eggs of laying hens, thereby entering the human food chain. Here, first the metabolism of fipronil was measured in vitro using chicken liver S9. The results show that fipronil is mainly metabolised into fipronil sulfone and the clearance obtained in vitro was extrapolated to in vivo liver clearance. In a second step a physiologically based kinetic model was developed with a focus on fipronil and its major sulfone metabolite and the model outcome was compared to available in vivo data in eggs from the literature. The experimentally obtained clearance was used as model input to evaluate whether such an in vitro-based model can be used in an early phase of a contamination incident to predict the time-concentration curves. Overall, all model predictions were within a 10-fold difference and the estimated elimination half-life for fipronil equivalents was 14 days. In vitro experiments are definitely recommended compared to in vivo studies, since they provide a fast first insight into the behaviour of a chemical in an organism.

Gynaecomastia linked to the intake of a herbal supplement fortified with diethylstilbestrol.

This study reports the findings of a supplement marketed on the Internet for prostate problems. The supplement was orally taken by a 60-year-old man with divergent hormonal levels and who was surgically treated for gynaecomastia: development of abnormally large mammary glands in males. The supplement showed a strong effect in a yeast oestrogen bioassay, expressing a yeast-enhanced green fluorescent protein (yEGFP) upon exposure to oestrogens. Using both nuclear magnetic resonance (NMR) and a gradient liquid chromatographic time-of-flight mass spectrometric (LC/TOF-MS) method, the response was shown to be caused by very high levels of diethylstilbestrol, known for causing gynaecomastia. The gynaecomastia was most probably caused by this orally taken 'natural' herbal supplement, as the patient's hormonal levels also returned to normal again when stopping the use of it. This case demonstrates that physicians need to be aware of the use of supplements with illegal components that may be responsible for unwanted side-effects.

Aflatoxin and liver cancer in Sudan.

This study investigated whether aflatoxin contamination of peanut products may contribute to the incidence of hepatocellular carcinoma (HCC) in Sudan. Thirty-seven peanut butter and peanut samples were collected from local markets. Aflatoxin concentrations were significantly higher in West Sudan [87.4 +/- 197.3 (SD) micrograms/kg], a high-risk area, than in Central Sudan (8.5 +/- 6.8 micrograms/kg), a low-risk area. In West Sudan, humid local storage conditions of peanut products were related to high aflatoxin concentrations. In a small case-control study of HCC patients (n = 24) and controls (n = 34), an odds ratio of 7.5 (95% confidence interval = 1.4-40.2) was observed for humid vs. dry local storage conditions. Development of an index of individual HCC exposure was less successful, probably because of year-to-year variability in aflatoxins in food. These preliminary findings justify further research into the role of aflatoxins and hepatitis in HCC incidence in Sudan.

Digestibility of casein, formaldehyde-treated casein and soya-bean protein in relation to their effects on serum cholesterol in rabbits.

Adult male rabbits were fed on semi-purified diets containing soya-bean protein isolate, casein or formaldehyde-treated casein as the protein source and 1 g cholesterol and 5 g of the non-absorbable marker chronic oxide/kg diet. The concentration of cholesterol in serum and in liver was increased on both the casein and formaldehyde-treated-casein diets. Excretion of bile acids and their concentration in faeces were lower in rabbits fed on casein or formaldehyde-treated casein when compared with rabbits fed on soya-bean protein. Apparent digestibility of nitrogen was lowest when formaldehyde-treated casein was fed, and highest on the casein diet. In rabbits fed on casein treated with formaldehyde, higher proportions of N were found in the water-soluble and trichloroacetic acid-insoluble protein fractions of the gastrointestinal tract contents compared with rabbits on the other two diets. Absorption of phosphate from the gastrointestinal tract was higher in rabbits fed on casein than in rabbits fed on soya-bean protein or formaldehyde-treated casein. The results indicate that, in rabbits, protein digestibility may not be an important determinant of serum cholesterol.