Pesticide residues in food — 2007: Toxicological ... - ipcs inchem

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Maximum concentrations in the blood were achieved at 2 h at the lower dose and 24 h at the
higher dose. Areas under the curve of blood concentration–time (AUC) were not different between
the sexes. The half-life in blood, assuming first-order kinetics, was approximately 150 h, independent
of sex and dose. Results from bile-cannulated animals showed approximately 88% absorption of the
lowest dose, on the basis of the excretion via urine (65%) and bile (7%) over 48 h and the amount
remaining in the carcass (16%); elimination via the faeces was about 3%. At the highest dose, elimination
via the urine and faeces during 168 h accounted for approximately 66% and 20%, respectively,
with approximately 85% excreted within the first 48 h.
Tissue concentrations from rats killed at four different time-points showed that the highest
concentrations of atrazine occurred in the liver, kidney and erythrocytes. Elimination from the tissues
was judged to be biphasic, and half-lives ranged from 59 to 300 h (assuming first-order kinetics).
Elimination from the erythrocytes was monophasic, with a half-life of 320 h. There were no significant
differences between the sexes or doses.
Whole-body autoradiography supported the previous toxicokinetic and tissue-residue data,
with slow elimination of radioactivity from well-perfused tissues (liver, kidney, lungs, heart and
spleen) owing to the presence of erythrocytes (Paul et al., 1993).
In a study on absorption, distribution, metabolism and elimination, two groups of four male
Fischer 344 rats received [ 14 C]atrazine ([U 14 C]-triazine labelled; radiochemical purity, > 98%; purity of
unlabeled atrazine, 99.6%) as a single oral dose at 30 mg/kg bw with or without pre-treatment with nonradiolabeled
tridiphane (purity, > 99%) as a single oral dose at 60 mg/kg bw. The plasma time-course
for the radiolabel exhibited a mono-exponential decrease for both treatment groups, with an absorption
and elimination half-life of approximately 3 h and 11 h, respectively. About 93% of the administered
radioactivity was recovered 72 h after dosing; with approximately 67% found in the urine and approximately
18% in the faeces, and less than 10% in the carcass, skin and erythrocytes. There were no
appreciable differences in the metabolite distribution between treatment groups, and the major urinary
metabolite of atrazine was found to be 2-chloro-4,6-diamino-1,3,5-triazine (64–67% of total urinary
radioactivity). S-(2-Amino-4-methylethylamino-1,3,5-triazin-6-yl)-mercapturic acid (13–14%), and
S-(2,4-diamino-1,3,5-triazin-6-yl)-mercapturic acid (9%) were tentatively identified based on similar
high-performance liquid chromatography (HPLC) retention times. The data indicated that there were
no meaningful differences in the absorption, distribution, metabolism, and excretion between rats given
only [ 14 C]atrazine and those given both tridiphane and [ 14 C]atrazine (Timchalk et al., 1990).
The slow elimination of [ 14 C]atrazine from rat tissue may in part be related to the extent of blood
perfusion of the tissue because a metabolite of s-triazines binds covalently to Cys-125 in the β-chain of
rodent haemoglobin rather than to the usually more reactive Cys-93, which is present in most mammalian
haemoglobins. The metabolite reacted also (but to a lesser extent) with haemoglobin from chicken
(Cys-126), but not with haemoglobin from humans, dogs, sheep, cows or pigs, which lack Cys-125
in their haemoglobin (Hamboeck et al., 1981). In Sprague-Dawley rats exposed to atrazine, it was
shown using matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-
TOF MS) that the adduct to Cys-125 of the β-chain of haemoglobin was DACT (G 28273) and not
parent atrazine or the mono-dealkylated metabolites G 28279 or G 30033 (Dooley et al., 2006).
Monkeys
In a study on the clearance of atrazine from the blood, four female Rhesus monkeys (aged
approximately 20–30 years) received [ 14 C]atrazine ([U 14 C]-triazine labeled; radiochemical purity,
98.1%; purity of unlabeled atrazine, 96.5%) intravenously as a single dose at 0.26 mg per monkey.
Samles of urine, faeces and blood were collected for 168 h after treatment. The principal route of
excretion was via the urine with approximately 63% of the administered dose being excreted within
ATRAZINE 37–138 JMPR 2007