High estrogenic fungus/mycotoxin found in dairy
Zearalenone is fairly rapidly absorbed following oral exposure (Dailey et al., 1980). Following a single oral dose of 10 mg zearalenone/kg body weight to 15 to 25 kg pigs, the absorption was approximated to be 80 to 85% (Biehl et al., 1993). Zearalenone and associated metabolites were found in the plasma of a pig in less than 30 minutes after initiating feeding with parent compound. Following zearalenone administration, zearalenone can be localized in reproductive tissues (ovary and uterus), adipose tissue and interstitial cells of the testes (Kuiper-Goodman et al., 1987). The reported biological half-life of total plasma zearalenone radioactivity following the oral dosage in pigs is 86 hours (Biehl et al., 1993). Zearalenone undergoes both phase I and phase II metabolism with involvement of 3α- and 3β-hydroxysteroid dehydrogenase enzymes catalyzing the first biotransformation step. Reduction of the keto group at C-6′ during phase I metabolism results in α- or β-zearalenol. Further reduction of the C11–C12 double bonds results in α- or β-zearalanol. Species differences in zearalenone susceptibility might be related to hepatic biotransformation, with the highest amount of α-zearalenol produced by pig hepatic microsomes, whereas chicken microsomes produced the highest amounts of β-zearalenol (Malekinejad et al., 2005). Humans metabolize zearalenone to α-zearalenol, a more estrogenic compound.
Pigs readily conjugated almost all absorbed zearalenone and α-zearalenol through glucuronidation. While the liver plays a major role in glucuronidation, the intestinal mucosa is active. Zearalenone was reduced to α- and β-zearalenol in sow intestinal mucosa homogenates (duodenum and jejunum) in vitro (Olsen et al., 1987). Gastrointestinal flora can aid in the metabolism of zearalenone. Zearalenone can undergo rumen metabolism, with reduction to mostly α-zearalenol and to a lower amount of β-zearalenol (Kiesseling et al., 1984). Whether rumen metabolism will increase or decrease zearalenone toxicity depends on absorption by the gastrointestinal tract, liver metabolism by hydroxysteroid dehydrogenase, and competition at the cytosolic estrogen receptor sites in the animal species.
Zearalenone undergoes extensive enterohepatic circulation and biliary excretion in most species. The major route of excretion for most species is through the feces, although rabbits primarily excrete zearalenone in the urine. Most zearalenone administered in a dose is excreted within a 72-hour period. Approximately 94% of radiolabeled zearalenone, given orally to white Leghorn laying hens at 10 mg/kg body weight, was eliminated through the excreta within 72 hours post-dosing (Dailey et al., 1980). No major retention of radiolabeled activity was found in edible muscle tissue, but lipophilic metabolite(s) were reported in egg yolk (at about 2 mg/kg concentration) 72 hours post-dosing.
Concern has focused on potential residue of zearalenone and its metabolites in milk, eggs and foods, and precocious development of sexual characteristics in young girls (Kuiper-Goodman et al., 1987; JECFA, 2001). Zearalenone and α- and β-zearalenols can be transmitted into the milk of sheep, cows and pigs administered high doses of zearalenone (Hagler et al., 1980; Mirocha et al., 1981). Hyperestrogenism has been reported in lamb and pig nursing dams dosed with zearalenone (Hagler et al., 1980; Palyusik et al., 1980). Dairy cows fed rations with purified zearalenone at 50 mg zearalenone/day and 165 mg zearalenone/day for 21 days had no detectable concentrations of zearalenone or α and β-zearalenol in the milk or plasma (Prelusky et al., 1990). One cow dosed with 544.5 mg zearalenone/day for 21 days had maximum concentrations of 2.5 ng zearalenone/ml and 3.0 ng α-zearalenol/ml in the milk. Cows dosed orally with a one-day dose of 1.8 or 6 g zearalenone had maximum milk levels on day 2 of 4.0 and 6.1 ng zearalenone/ml, respectively. This research indicates that minimal transmission of zearalenone occurs into milk and only for a short period of time after exposure to high concentrations of zearalenone.
Following intubations of tritiated zearalenone into the crops of 7-week-old broiler chickens, the greatest accumulation of radioactivity occurred in the liver 30 minutes post-administration, which became a trace of radioactivity by 48 hours post-administration (Mirocha et al., 1982). Only zearalenone was detected in muscle tissue at approximately 4 ppb at 48 hours post-administration, indicating the zearalenone residues in edible tissue is minimal.