Invited review: Efficacy, metabolism, and toxic responses to chlorate salts in food and laboratory animals.

For over 100 yr, scientists have explored uses of sodium chlorate in agricultural applications. Sodium chlorate is a strong oxidizer, and thus can be very hazardous when not handled accordingly. Nevertheless, late 19th century agriculturists and scientists attempted to exploit the chemical properties of sodium chlorate as an herbicide and food preservative. It is the herbicidal utility that led to subsequent use of sodium chlorate in the agricultural industry since then. However, in 2000, USDA-ARS scientists proposed a new and targeted use of sodium chlorate against enterobacteria in food animal production. Specifically, when orally dosed in to cattle (Bos taurus), swine (Sus scrofa), broilers (Gallus gallus), turkeys (Meleagris gallopavo), and sheep (Ovis aries), chlorate reduced the fecal shedding of common enteropathogens of the Enterobacteriaceae family. Subsequent to this discovery, the efficacy of chlorate salts has been demonstrated in numerous production classes within species. Doses of sodium chlorate as low as 30 mg/kg BW, but typically 50 to 150 mg/kg BW, have been used to demonstrate efficacy against pathogens. Single or short-duration (<3 d) exposures to oral chlorate at concentrations < 150 mg/kg BW have not produced acute toxicity or clinical signs (labored breathing, methemoglobinemia) in food animals. In all species studied to date, the major biotransformation product of chlorate is chloride ion; chlorite is not present in tissues or excreta of chlorate dosed animals. Chlorate is rapidly eliminated in ruminants and nonruminants, primarily in urine; likewise, residual chlorate in tissues depletes rapidly. Application of any new chemical entity to food animal production carries with it a responsibility to understand adverse reactions that intended and nonintended exposures may have in target and (or) nontarget animals and an understanding of the pathways of elimination that occur after exposure. Therefore, the purpose of this review is to summarize the published data regarding the efficacy, metabolism, and toxicology of chlorate salts in target (livestock) and nontarget species.

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.

The in vitro reduction of sodium [36Cl]chlorate in bovine ruminal fluid.

Sodium chlorate effectively reduces or eliminates gram-negative pathogenic bacteria in the gastrointestinal tracts of live cattle. Limitations to the in vivo efficacy of chlorate are its rapid absorption from the gastrointestinal tract and its presumed reduction to chloride within the gastrointestinal tract. We hypothesized that chlorate would be reduced via ruminal bacteria in a ruminal in vitro system and that the reduction of chlorate would be influenced by the dietary for-age:concentrate ratio; thus, 4 ruminally cannulated steers were fed 20 or 80% concentrate diets in a crossover design. Ruminal fluid was collected in 2 periods and dispensed into in vitro tubes containing sodium [36Cl]chlorate, which was sufficient for 100 or 300 mg/L final chlorate concentrations. The tubes were incubated for 0, 1, 4, 8, 16, or 24 h; autoclaved, control ruminal fluid, fortified with sodium [36Cl]chlorate, was incubated for 24 h. Chlorate remaining in each sample was measured by liquid scintillation counting after [36Cl]chloride was precipitated with silver nitrate. A preliminary study indicated that chlorite, a possible intermediate in the reduction of chlorate, had a half-life of approximately 4.5 min in freshly collected (live) ruminal fluid; chlorite was, therefore, not specifically measured in ruminal incubations. The chlorate dose did not affect in vitro DM digestion (P > or = 0.11), whereas in vitro DM digestibility was decreased (P < or = 0.05) by 80% forage content. By 24 h, 57.5 +/- 2.6% of the chlorate remained in 100-mg/L incubations, whereas 78.2 +/- 2.6% of the chlorate remained in the 300-mg/L incubations. When the data were expressed on a concentration basis (mg/L), diet had no effect (P > or = 0.18) on chlorate reduction; however, when chlorate reduction was expressed on a percentage basis, chlorate reduction tended to be greater (P > or = 0.09) at 8 and 16 h in the incubations containing the low-concentrate diet. Chlorate remaining in autoclaved controls at 24 h was intermediate (P < 0.01) between chlorate remaining in live ruminal fluid samples incubated for 0 or 24 h. Attempts to isolate chlorate-respiring bacteria from 2 sources of ruminal fluid were not successful. These data indicate that microbial-dependent or chemical-dependent, or both, reduction of chlorate occurs in bovine ruminal fluid and that dietary concentrate had a negligible effect on chlorate reduction.

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

The objectives of this study were to determine total radioactive residues and chlorate residues in edible tissues of cattle administered at three levels of sodium [36Cl]chlorate over a 24-h period and slaughtered after a 24-h withdrawal period. Three sets of cattle, each consisting of a heifer and a steer, were intraruminally dosed with a total of 21, 42, or 63 mg of sodium [36Cl]chlorate/kg of body weight. To simulate a 24-h exposure, equal aliquots of the respective doses were administered to each animal at 0, 8, 16, and 24 h. Urine and feces were collected in 12-h increments for the duration of the 48-h study. At 24 h after the last chlorate exposure, cattle were slaughtered and edible tissues were collected. Urine and tissue samples were analyzed for total radioactive residues and for metabolites. Elimination of radioactivity in urine and feces equaled 20, 33, and 48% of the total dose for the low, medium, and high doses, respectively. Chlorate and chloride were the only radioactive chlorine species present in urine; the fraction of chlorate present as a percentage of the total urine radioactivity decreased with time regardless of the dose. Chloride was the major radioactive residue present in edible tissues, comprising over 98% of the tissue radioactivity for all animals. Chlorate concentrations in edible tissues ranged from nondetectable to an average of 0.41 ppm in skeletal muscle of the high-dosed animals. No evidence for the presence of chlorite was observed in any tissue. Results of this study suggest that further development of chlorate as a preharvest food safety tool merits consideration.

Certification. Hospital versus national standards.

"Certification" and "credential" are frequently used terms in nursing. How these terms are used and what they mean to nursing practice is the focus of this article. Definitions, history, and application of these concepts are explored. Recommendations are made that a hospital not assume responsibility for the granting of certification or credentials to nursing staff members. Nurses and nursing administrators are urged to support nationally recognized certification programs.

A sensorimotor program for improving writing readiness skills in elementary-age children.

This article discusses a writing readiness program used with three groups of children aged 5 to 7 years. The program combines occupational therapy treatment with a supplementary program implemented by school personnel or parents. The Developmental Test of Visual-Motor Integration-Revised (Beery, 1982) was used to measure the developmental level of the children's writing readiness skills before and after treatment. The group of children with a significant verbal performance IQ discrepancy (greater than 15 points) showed a 17-month growth in readiness skills within 1 year. The group of children with mental retardation (IQ less than 80) showed a significant sex effect: The boys showed more gains than the girls. Implications of these findings are discussed.