Page 1124 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

1056 SECTION | XV Mycotoxins

VetBooks.ir OH O 11′ CH 3 H compared to α-zearalanol and zearalenone produced by pig
whereas
microsomes
microsomes,
hepatic
chicken
produced the highest amounts of β-zearalenol, which has
3 2 1 O 10′ lower estrogenic activity (Malekinejad et al., 2006;
4 6 Zimedine et al., 2007). Zearalenone and its metabolites are
5 8′
HO 1′ conjugated with glucuronic acid (Malekinejad et al., 2006;
Pfeiffer et al., 2010). Pigs readily conjugated almost all
2′ 6′
3′ absorbed zearalenone and α-zearalenol through glucuroni-
O dation. While the liver plays a major role in glucuronida-
tion, the intestinal mucosa is also active. Zearalenone was
FIGURE 76.1 Chemical structure of zearalenone.
reduced to α-and β-zearalenol in sow intestinal mucosa
homogenates (duodenum and jejunum) in vitro (Olsen
such as α- and β-zearalenols, zearalenone is commonly
et al., 1987). Cytochrome P450 may also be involved
detected in grains with another Fusarium mycotoxin
in zearalenone metabolism (EFSA, 2011). Gastrointestinal
deoxynivalenol. Zearalenone is heat stable, but can be
flora can aid in the metabolism of zearalenone.
partially destroyed during extrusion cooking of cereals
Zearalenone can undergo rumen metabolism, with reduc-
(Castells et al., 2005).
tion to mostly α-zearalenol and to a lower amount of
β-zearalenol (Kiessling et al., 1984). Whether rumen
metabolism will increase or decrease zearalenone toxicity
TOXICOKINETICS
depends on absorption by the GIT, liver metabolism by
The toxicokinetics of zearalenone have been reported in hydroxysteroid dehydrogenase, and competition at the
several species following different routes of its administra- cytosolic receptor sites in the animal species.
tion (Prelusky et al., 1989; Mallis et al., 2003; Da ¨nicke Zearalenone undergoes extensive enterohepatic
et al., 2005; Shin et al., 2009a,b,c; Devreese et al., 2015). circulation and biliary excretion in most species (Biehl
Studies in animals indicate rapid absorption of zearalenone et al., 1993; Shin et al., 2009a,b). The major route of
from the gastrointestinal tract (GIT) following oral expo- excretion for most species is through the feces, although
sure (Dailey et al., 1980). Oral bioavailability is very low rabbits primarily excrete zearalenone in the urine. Most
in poultry and rats (,10%) due to extensive metabolism zearalenone administered in a dose is excreted within a
(Fitzpatrick et al., 1988; Zimedine et al., 2007; Shin et al., 72-h period. Approximately 94% of radiolabeled zeara-
2009a; Devreese et al., 2015). Following a single oral dose lenone, given orally to White Leghorn laying hens at
of 10 mg zearalenone/kg body wt to 15 25 kg pigs, the 10 mg/kg body wt, was eliminated through the excreta
absorption was approximated to be 80% 85% (Biehl within 72 h postdosing (Dailey et al., 1980). No major
et al., 1993). Once entered in the body, zearalenone is retention of radiolabeled activity was found in edible
mainly metabolized in the liver, which seems to be one of muscle tissue, but lipophilic metabolite(s) were reported
the main targets of the toxin (Zimedine et al., 2007; Jiang in egg yolk (at about 2 mg/kg concentration) 72 h
et al., 2012; Koraichi et al., 2012). In liver, zearalenone postdosing.
could impact maternal and fetal liver to ABC transporters Concern has focused on potential residue of zearalenone
substrates, and influence fetal development through nuclear and its metabolites in milk, eggs, and foods and precocious
receptor modulation (Koraichi et al., 2012). Zearalenone is development of sexual characteristics in young female girls
also distributed to various other tissues including, kidney, (Kuiper-Goodman et al., 1987; JECFA, 2000; Massart
adipose tissue, and estrogen target tissues, such as the et al., 2008). Zearalenone and α-and β-zearalenols can be
uterus, testes, and ovarian follicles (Liang et al., 2015; transmitted into the milk of sheep, cows, and pigs adminis-
Mally et al., 2016). In pigs, zearalenone and its metabolites tered high doses of zearalenone (Hagler et al., 1980;
were found in the plasma of a pig in less than 30 min after Mirocha et al., 1981). Hyperestrogenism has been reported
initiating feeding with the parent compound. Once admin- in lambs and pigs nursing dams dosed with zearalenone
istered, zearalenone can be localized in reproductive tissues (Hagler et al., 1980; Palyusik et al., 1980; Smith et al.,
(ovary and uterus) (Gajecka et al., 2012), adipose tissue, 1990). Dairy cows fed rations with purified zearalenone at
and interstitial cells of the testes (Ueno et al., 1977; 50 mg zearalenone/day and 165 mg zearalenone/day for 21
Kuiper-Goodman et al., 1987).Thereportedbiological days had no detectable concentrations of zearalenone or α-
half-life of total plasma zearalenone radioactivity following and β-zearalenol in the milk or plasma (Prelusky et al.,
oral dosage in pigs is 86 h (Biehl et al., 1993). Species dif- 1990). One cow dosed with 544.5 mg zearalenone/day for
ferences in zearalenone susceptibility might be related to 21 days had maximum concentrations of 2.5 ng zearale-
hepatic biotransformation, with the highest amount of none/mL and 3.0 ng α-zearalanol/mL in the milk. Cows
α-zearalenol, which has increased estrogenic activity dosed orally with a 1-day dose of 1.8 or 6 g zearalenone