Title: Kinetics and disposition of orally dosed sodium chlorate in sheep Authors
Submitted to: Journal of Animal Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: December 17, 2011
Publication Date: December 28, 2011
Citation: Smith, D.J., Taylor, J.B. 2012. Kinetics and disposition of orally dosed sodium chlorate in sheep. Journal of Animal Science. 90:2026-2034. Interpretive Summary: Sodium chlorate is of interest to food producers because it reduces the occurrence of pathogens such as E. coli and Salmonella in the lower digestive tracts and feces of food animals. These bacteria can negatively affect animal and human health. This study was conducted to determine the rate at which sodium chlorate is removed from digestive tracts of sheep so that proper dosing procedures can be developed. Additional objectives were to determine how rapidly chlorate is excreted in urine and feces and to determine if chlorate is secreted into milk of lactating sheep. After oral administration to sheep, sodium chlorate was very rapidly removed from the digestive tract by absorption. Within about 2 hours, over 90% of the oral doses had been absorbed. After absorption, chlorate was rapidly cleared from the blood by excretion into the urine. Only small amounts of chlorate were excreted into feces of orally dosed sheep. In milking animals, chlorate was also secreted into milk but not to the extent that it was eliminated in urine. An important, and perhaps surprising, finding was that relatively small amounts of the chlorate dose remained in the digestive tracts and feces of orally dose animals. These results suggest that chlorate affects processes within the body that ultimately affect pathogens that are present in the lower digestive tract.
Technical Abstract: 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 h 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 not detectable to 0.2 ppm at 24, 48, and 72 h, respectively, in serum of treated animals; in feces, residues averaged 29 to 82, 0.8 to 14, and not detectable to 1.2 ppm 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, 24to 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 ppm during the first and last collection periods, respectively. Urine contained the greatest concentration of chlorate at each time point and averaged 480 ± 268 ppm 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 drawn for 48 h and urine samples were collected in 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.