Metabolism sulfoconjugated forms of AFM1 AFQ1 and AFP1 for review Guengerich et al 1998

Absorption of aflatoxin B1 administrated by oral route is rapid and almost complete (Gregory, Goldstein, & Edds, 1983). Absorption takes place in the

Table 4.3 EU regulation for aflatoxins contamination (mg/kg)

Destination Toxin

Matrix

Maximal concentration (mg/kg)

Human food

Aflatoxin B1

Aflatoxins

Animal feed

Aflatoxin M1

Aflatoxin B1

Groundnuts + grains + dry fruits Cereals

Spices

Cereal-based foods for young children Groundnuts + grains + dry fruits Cereals

Spices Milk

Preparation for young children Raw material for animal feeds Compound feeds

2, 5 or 8 depending on the product and the processing step

2 or 5 depending on the product and the processing step

4, 10 or 15 depending on the product and the processing step

4 or 10 depending on the product and the processing step

0.05

0.025

5-20 depending on animal species small intestine, mainly in jejunum (Kumagai, 1989). In plasma, AFB1 is strongly linked to albumin, part of this fixation being covalent. Then, AFB1 goes through the liver where most part of the toxin is going to be metabolized, only 1-10% of the AFB1 staying fixed to macromolecules. AFB1 is a lipophilic molecule that will go through classical phase I and II biotransformation process. Main phase I metabolites are epoxide, hydroxyled compounds AFM1, AFQ1, AFP1, a reduced compound: aflatoxicol (AFL), a hydrogenated and hydroxylated molecule: AFB2a (Fig. 4.1). The most important phase II metabolites of the epoxide derivative are conjugated with GSH and glucorono- and sulfo-conjugated forms of AFM1, AFQ1 and AFP1.

Epoxide formation can be considered as a bioactivation process due to the very high reactivity of this molecule with liver macromolecules. Other metabolic pathways may be considered as detoxification leading to compounds without any toxicity (AFQ1, AFP1, AFB2a) or that keep residual toxicity (AFM1 and aflatoxicol).

Excretion of aflatoxins is quite slow (70-80% of a single dose in 4 days), biliary excretion being the most important route (50%) and AFM1 the major excreted metabolite.

Fig. 4.1 Phase I metabolism of aflatoxin B1 (Paterson, 1977)
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