INVITED REVIEW: Efficacy, metabolism, and toxic responses to chlorate salts in food and laboratory animals1

Abstract

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.

Chlorate Specifically Targets Oxidant-Starved, Antibiotic-Tolerant Populations of Pseudomonas aeruginosa Biofilms

“…Thus, chlorate is expected to be nontoxic to cells lacking Nar (e.g., mammalian cells) and specifically kill Nar-containing bacterial cells via cytoplasmic chlorite production. Consistent with this logic, chlorate has been successfully used to control pathogens in studies of agricultural systems, where livestock that ingested chlorate had lowered intestinal and fecal enteric-pathogen counts ( 57 ). Importantly, the treated animals showed no measurable health effects with very high quantities of ingested chlorate (e.g., 250 mg kg −1 of body weight per day [ 58 ]), including in one study in which serum chlorate concentrations reached 1 mM in sheep ( 59 ).…”

Inhibition of multidrug‐resistant Staphylococci by sodium chlorate and select nitro‐ and medium chain fatty acid compounds

“…; Smith et al . ). In lactating sheep, for instance, administration of 450 mg of sodium chlorate per kg body weight resulted in milk containing approximately 3 μ mol ml −1 (287 μ g ml −1 ) chlorate in samples collected after 0–8 h of administration (Smith and Taylor ).…”

A review of strategies to impact swine feed biosecurity

“…As a result, a number of different products have been tested as chemical-based feed hazard mitigants. Some compounds that have shown mixed efficacy at reducing or eliminating virus or bacterial risk include organic acids (Eklund 1985), essential oils (Orhan et al ., 2012), sodium bisulfate (Knueven, 1998), or sodium chlorate (Smith et al ., 2012); however, the cumulative data suggest that the effectiveness of any chemical-based feed mitigant is not only target specific but also feed ingredient/matrix specific (Cochrane, 2018). Of all the potential chemical mitigants available, the two that have garnered the most commercial interest are formaldehyde and MCFAs.…”