Page 1136 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

1068 SECTION | XVI Feed and Water Contaminants

VetBooks.ir NH 2 OH tissue melamine concentrations in chickens fed
melamine-containing diets were found in the kidneys,
with lower concentrations in the liver and muscle (Bai
N
N
N
N
et al., 2010; Suknikom et al., 2016; Zapletal et al., 2016).
Tissue residues were depleted 10 20 days after exposure
H N N NH 2 HO N OH ceased (Bai et al., 2010). Melamine administered to preg-
2
Melamine Cyanuric acid nant rats was detected in the placenta and fetuses (Jingbin
et al., 2010).
FIGURE 77.1 Structural formulas of melamine and cyanuric acid. Melamine concentrations were detected in catfish and
trout within 1 day of dosing, and the half-life of melamine
the largest melamine producer, produces a quarter of the in skeletal muscle of fish ranged from 1.5 to 4 days
melamine used in the world. (Reimschuessel et al., 2009). Due to the longer elimina-
Cyanuric acid, often found as a cocontaminant with tion half-life of melamine and cyanuric acid in fish, these
melamine, is an intermediate produced during melamine compounds do not need to be given together. Melamine
manufacture and degradation. It is commonly used to can be given 1 3 days after cyanuric acid (dependent on
stabilize chlorine in swimming pools and in the manufac- fish species) and produce crystals, and cyanuric acid can
ture of bleach, disinfectants, and herbicides (Dalal and be given 7 14 days (dependent on species) after mela-
Goldfarb, 2011). mine and produce crystals (Reimschuessel et al., 2010).
Melamine is excreted by dairy cattle into milk, particu-
larly in high-producing cattle, though milk yield and com-
PHARMACOKINETICS/TOXICOKINETICS
position are otherwise unaffected. Melamine can be
Melamine is minimally, if at all, metabolized in most detected in milk within 8 h of exposure and remains
monogastric mammals, but could be partially metabolized detectable until 4 days after cessation of exposure. Transfer
in the rumen of cattle and small ruminants. There is some efficiency from feed to cows’ milk was calculated to be
evidence of metabolism of melamine to cyanuric acid in between 0.66% and 0.95% and was not dependent on mel-
poultry (Suchy ´ et al., 2014). Approximately 90% 95% of amine dose (Shen et al., 2010). Approximately 0.3% of a
ingested melamine is absorbed in chickens and ducks melamine dose was excreted in milk in dairy goats, and
(Poapolathep et al., 2015; Suknikom et al., 2016). milk melamine concentrations remained above the level of
Melamine does not accumulate over time in the animal concern (1.0 μg/mL) until 3 days after cessation of dosing
body. The half-life for urinary elimination of melamine is (Baynes et al., 2010).
given as 6 h in dogs and approximately 4 h in swine Melamine fed to chickens is deposited within eggs
(Lipschitz and Stokey, 1945; Yang et al., 2011). Renal within a day or 2 days postexposure (Chen et al., 2010;
elimination of unchanged melamine is almost complete Bai et al., 2010). The melamine concentration in eggs is
after 32 h in poultry (Poapolathep et al., 2015). Therefore, proportional to the dietary concentration; a dietary con-
melamine should be almost completely excreted within 2 centration of 164 ppm could produce an actionable mela-
days of the last exposure in these monogastric mammals mine concentration in eggs of 2.5 ppm (Chen et al.,
and birds; however, crystals were seen microscopically in 2010). A 4-day withdrawal period has been recommended
feline kidneys 8 weeks after dietary exposure to melamine for eggs from melamine-exposed chickens, though trace
and cyanuric acid (Cianciolo et al., 2008). The elimina- concentrations of melamine remain detectable in eggs for
tion half-life of melamine in small ruminants is three- to about 9 days after exposure ceases (Yang et al., 2011).
sixfold slower than in monogastrics, possibly due to pro-
longed sequestration in the rumen (Baynes et al., 2010). MECHANISM OF ACTION
Urinary excretion accounted for 54.1% of melamine
administered to sheep, and 23.7% was found in the feces Though previous animal studies found that both melamine
(Cruywagen et al., 2011). and cyanuric acid were relatively nontoxic when given
Detectable melamine concentrations have been individually, they caused crystal formation in renal
reported in edible tissues from animals. It was estimated tubules of mammals when given together (Puschner and
that 3.6% of melamine fed to sheep partitioned to muscle Reimschuessel, 2011). Melamine and cyanuric acid crys-
(Cruywagen et al., 2011). Melamine concentrations in the tallize, forming a molecular lattice structure, at a pH of
kidney were higher than concentrations in the skeletal 5.8 (Osborne et al., 2008; Bhalla et al., 2009). Crystals
muscle or liver in lambs, and these concentrations recovered from kidneys and urine of cats that ingested
decreased below 20 ppb 4 days after cessation of expo- melamine-contaminated food contained 70% cyanuric
sure, but addition of cyanuric acid to the diet did not acid and 30% melamine, based on infrared spectra results
affect melamine deposition (Lv et al., 2010). The highest (Osborne et al., 2008; Thompson et al., 2008).