Kinetics and disposition of orally dosed sodium chlorate in sheep.

Experiments were conducted in sheep to determine excretory characteristics of sodium chlorate after a single oral dose. In Exp. 1, lambs (n = 16; age = 8.1 ± 1.7 d; BW = 8.2 ± 1.1 kg; mean ± SD) were dosed orally with 0, 30, 60, or 90 mg/kg BW of sodium chlorate. Twenty-four hours after exposure chlorate residues were dose dependent (P < 0.05) in small intestinal contents, serum, and urine, but chlorate residues were not consistently detected in cecal or colonic contents. In Exp. 2, non-pregnant yearling ewes (BW = 74.8 ± 5.6 kg; mean ± SD) were orally dosed with 0, 150, 300, or 450 mg/kg BW of sodium chlorate. Across dose, chlorate residues averaged from 47 to 114, 0.6 to 4.5, and were not detectable to 0.2 µg/mL at 24, 48, and 72 h, respectively, in serum of treated animals; in feces, residues averaged 29 to 82, 0.8 to 14, and were not detectable to 1.2 µg/mL at the same respective time periods. In Exp. 3, six lactating ewes (BW = 76.3 ± 8.0 kg) were dosed orally with 450 mg/kg BW of sodium chlorate; residues were measured in serum, milk, urine and feces in periods encompassing 0 to 8, 8 to 16, 16 to 24, 24 to 32, 32 to 40, and 40 to 48 h. Chlorate residues in milk were detectable at all time periods with concentrations averaging from 287 ± 67 to 26 ± 13 µg/mL during the first and last collection periods, respectively. Urine contained the greatest concentration of chlorate at each time point and averaged 480 ± 268 µg/mL at 40 to 48 h. Depletion half-lives in serum, milk, urine, and feces were estimated to be 6.2, 27, 19, and 10 h, respectively; milk, urinary and fecal half-lives are likely overestimated due to the fact that 8-h sample pools were used in half-life estimations. In Exp. 4, three wethers (BW = 87.1 ± 5.3 kg) each were orally dosed with 14 or 42 mg/kg BW of sodium chlorate; blood samples were serially collected for 48 h, and urine samples were collected at 0 to 8, 8 to 16, 16 to 24, 24 to 36, and 36 to 48 h. Estimates of absorption and elimination half-lives based on serum chlorate concentrations were about 0.4 and 2.5 h, respectively. Urine collected during the 6 h immediately following dosing contained the greatest concentrations of chlorate residues relative to subsequent collection periods. Rapid removal of chlorate from the gastrointestinal lumen suggests that effects of chlorate on colonic and fecal gastrointestinal bacteria may occur through mechanisms other than direct luminal contact between microbe and chlorate salts.

Pharmacokinetics of ruminally dosed sodium [36Cl]chlorate in beef cattle.

The recently recognized potential of sodium chlorate as a possible preharvest food safety tool for pathogen reduction in meat animals has spurred interest in the pharmacokinetics of intraruminally dosed chlorate. Six Loala cattle were assigned (one heifer and one steer per treatment) to one of three intraruminal doses of radiolabeled sodium [36Cl]chlorate (21, 42, or 63 mg/kg body weight) administered in four equal aliquots over a 24-h period. Blood and serum were collected (29 samples in 48 h). Total radioactive residues were measured and the radioactive moieties were speciated. Chlorate appeared rapidly in blood and serum after dosing. For animals administered a dose of 42 or 63 mg/kg, the half-life of absorption was estimated at 0.6-0.9 h. Serum chlorate concentrations progressively increased with aliquot administration until peaking at 6-21 parts per million at 26 h. Between aliquot administrations, serum chlorate levels typically peaked in 3.5 h or less. The half-life of chlorate elimination ranged between 6.9 and 11 h, depending on the dose. Ultimately, absorption of chlorate removes it from its desired site of action, the lower gastrointestinal tract, thereby reducing its efficacy. Further research is needed to develop a chlorate formulation that will allow passage to the lower gastrointestinal tract.

Tissue residues, metabolism, and excretion of radiolabeled sodium chlorate (Na[36Cl]O3) in rats.

A novel preharvest technology that reduces certain pathogenic bacteria in the gastrointestinal tracts of food animals involves feeding an experimental sodium chlorate-containing product (ECP) to animals 24-72 h prior to slaughter. To determine the metabolism and disposition of the active ingredient in ECP, four male Sprague-Dawley (approximately 350 g) rats received a single oral dose of sodium [36Cl]chlorate (3.0 mg/kg body weight). Urine, feces, and respired air were collected for 72 h. Radiochlorine absorption was 88-95% of the administered dose, and the major excretory route was the urine. Parent chlorate was the major species of radiochlorine present in urine at 6 h (approximately 98%) but declined sharply by 48 h (approximately 10%); chloride was the only other species of radiochlorine detected. Except for carcass remains (4.6% of dose), skin (3.2%), and gastrointestinal tract (1.3%), remaining tissues contained relatively low quantities of radioactivity, and >98% of radiochlorine remaining in the liver, kidney, and skeletal muscle was chloride. Chlorite instability was demonstrated in rat urine and bovine urine. The previously reported presence of chlorite in excreta of chlorate-dosed rats was shown to be an artifact of the analytical methods employed. Results from this study indicate that chlorate is rapidly absorbed and reduced to chloride, but not chlorite, in rats.

Effect of sodium [36Cl]chlorate dose on total radioactive residues and residues of parent chlorate in growing swine.

An experimental chlorate-based product has been shown to be efficacious in eliminating economically important, Gram-negative human pathogens in the gastrointestinal tracts of food animals. Prior to the commercial marketing of such a product, the magnitude and chemical nature of residues remaining in edible tissues must be determined. Thus, the objective of this study was to determine the tissue distribution and elimination of sodium [36Cl]chlorate in orally dosed swine. Three sets of pigs, each consisting of a barrow and a gilt, were orally dosed with a total of 20, 40, or 60 mg of sodium [36Cl]chlorate per kg body weight via the drinking water. Urine and feces were collected throughout the 30 h study. Twenty-four hours after the last exposure to [36Cl]chlorate, each pig was harvested and both edible and inedible tissues were collected. Urine and tissue samples were analyzed for total radioactive residues and for chlorate metabolites. Elimination of radioactivity in urine averaged 81.6, 83.7, and 83.9% of the total dose for the low, medium, and high doses, respectively. Fecal elimination of radioactivity averaged 1.1% of the dosed radiochlorine across all doses. Parent chlorate always represented greater than 97.4% of the urinary radiochlorine with the remaining radiochlorine being excreted as chloride ion. Chlorate represented 39-77% of fecal radioactivity, depending upon dose. Chlorate concentrations in edible tissues ranged from 0.01 to 0.49 ppm, with residues in liver and skeletal muscle generally lower than those in kidney and adipose tissue. Chlorate residues were concentrated in thyroid tissues (7.7-25.4 ppm) relative to edible tissues. No evidence for the presence of chlorite was observed in excreta or in tissues. Results of this study suggest that further development of chlorate as a preharvest food safety tool in swine merits consideration.

Tissue distribution, elimination, and metabolism of dietary sodium [36Cl]chlorate in beef cattle.

Two steers (approximately 195 kg) were each dosed with 62.5 or 130.6 mg/kg body weight sodium [36Cl]chlorate for three consecutive days. All excreta were collected during the dosing and 8 h withdrawal periods. The apparent radiochlorine absorption was 62-68% of the total dose with the major excretory route being urine. Parent chlorate was 65-100% of the urinary radiochlorine; chloride was the only other radiochlorine species present. Similarly, residues in edible tissues were composed of chloride and chlorate with chloride being the major radiolabeled species present. Chlorate represented 28-57% of the total radioactive residues in skeletal muscle; in liver, kidney, and adipose tissues, chlorate ion represented a smaller percentage of the total residues. Chlorate residues in the low dose steer were 26 ppm in kidney, 14 ppm in skeletal muscle, 2.0 ppm in adipose tissue, and 0.7 ppm in liver. These data indicate that sodium chlorate may be a viable preharvest food safety tool for use by the cattle industry.