Following a request from the European Commission, the risks to human health related to the presence of chlorate in food were assessed by the EFSA Panel on Contaminants in the Food Chain (CONTAM Panel). The presence of chlorate in food can arise from the use of chlorinated water for food processing and the disinfection of foodprocessing equipment. Inhibition of iodine uptake in humans was identified as the critical effect for chronic exposure to chlorate. A tolerable daily intake (TDI) of 3 μg chlorate/kg body weight (b.w.) was set by readacross from a TDI of 0.3 μg/kg b.w. derived for this effect for perchlorate, multiplied by a factor of 10 to account for the lower potency of chlorate. Formation of methaemoglobin was identified as the critical acute effect of chlorate. An acute reference dose (ARfD) of 36 μg chlorate/kg b.w. was derived from a no-observedeffect-level for chlorate in a controlled clinical study. Chronic exposure of adolescent and adult age classes did not exceed the TDI. However, at the 95th percentile the TDI was exceeded in all surveys in ‘Infants’ and ‘Toddlers’ and in some surveys in ‘Other children’. Chronic exposures are of concern in particular in younger age groups with mild or moderate iodine deficiency. Mean and 95th percentile acute exposures were below the ARfD for all age groups indicating no concern. Based on the current practices in food industry, application of a hypothetical maximum residue limit (MRL) of 0.7 mg/kg for all foodstuffs and drinking water would only minimally reduce acute/chronic exposures and related risks. Assuming chlorate concentrations of 0.7 mg/kg for all foods and drinking water consumed in a day, acute exposures would increase by up to about 5-fold and the ARfD be exceeded at mean estimates in ‘Infants’ and ‘Toddlers’ and at 95th percentile also in ‘Other children’and ‘Adults’. © European Food Safety Authority, 2015

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EFSA CONTAM Panel (EFSA Panel on Contaminants in the Food Chain), 2015. Scientific Opinion on risks for public health related to the presence of chlorate in food

Chlorine dioxide (ClO2) is an effective drinking water disinfectant, but sodium chlorate (NaClO3) has been identied as a potentially harmful disinfection by-product. Studies were performed to describe the developmen t of thyroid lesions in animals exposed to NaClO3 in the drinking water. Male and female F344 rats and B6C3F1 mice were exposed to 0, 0.125, 0.25, 0.5, 1.0, or 2.0 g/L NaClO3 for 21 days. Additional male F344 rats were exposed to 0, 0.001, 0.01, 0.1, 1.0, or 2.0 g/L NaClO3 for 90 days. Female F344 rats were exposed to 0, 0.5, 1.0, 2.0, 4.0, or 6.0 g/L of NaClO3 for 105 days. Thyroid tissues were processed by routine methods for light microscopic examination, and follicular cell hyperplasia was diagnosed using a novel method. Thyroid hormone levels were altered signicantly after 4 and 21 days. NaClO 3 treatment induced a concentration-dependen t increase in the incidence and severity of thyroid follicular cell hyperplasia. Male rats are more sensitive to the effects of NaClO3 treatment than females. Follicular cell hyperplasi a was not present in male or female B6C3F1 mice. These data can be used to estimate the human health risk that would be associated with using ClO2, rather than chlorine, to disinfect drinking water.

Subchronic sodium chlorate exposure in drinking water results in a concentration-dependent increase in rat thyroid follicular cell hyperplasia.

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.

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

Sodium chlorate (NaClO3 ) is a widely used nonselective herbicide. It is also generated as a by-product during disinfection of drinking water by chlorine dioxide. The purpose of this study was to evaluate the effect of NaClO3 on rat intestine. Adult male rats were randomly divided into five groups: control and remaining four groups were administered orally different doses of NaClO3 and sacrificed 24 h after the treatment. The administration of NaClO3 produced acute oxidative stress in the intestine, which manifested in the form of markedly enhanced malondialdehyde levels and carbonyl content and lowered total sulfhydryl groups and glutathione levels. The activities of several brush border membrane (BBM) enzymes were greatly reduced as compared to control. There were alterations in the activities of various enzymes of carbohydrate metabolism and those involved in maintaining the antioxidant defense system. Histological studies support the biochemical results showing NaClO3 dose-dependent increase in tissue damage. Thus, the present study shows that oral administration of NaClO3 decreases the activities of BBM enzymes, induces oxidative stress, alters metabolic pathways, and impairs the antioxidant system of rat intestine. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1607-1616, 2017.

Sodium chlorate, a major water disinfection byproduct, alters brush border membrane enzymes, carbohydrate metabolism and impairs antioxidant system of Wistar rat intestine.

P J Kelly

Papers

Toxicity of sodium chlorate to the dog.