Absorption and disposition of bromate in F344 rats

MoBull Consulting, Richland, WA, USA.
Toxicology (Impact Factor: 3.75). 06/2012; 300(1-2):83-91. DOI: 10.1016/j.tox.2012.06.002
Source: PubMed

ABSTRACT Bromate (BrO(3)(-)) is a ubiquitous by-product of using ozone to disinfect water containing bromide (Br(-)). The reactivity of BrO(3)(-) with biological reductants suggests that its systemic absorption and distribution to target tissues may display non-linear behavior as doses increase. The intent of this study is to determine the extent to which BrO(3)(-) is systemically bioavailable via oral exposure and broadly identify its pathways of degradation. In vitro experiments of BrO(3)(-) degradation in rat blood indicate a rapid initial degradation immediately upon addition that is >98% complete at concentrations up to 66μM in blood. As initial concentrations are increased, progressively lower fractions are lost prior to the first measurement. Secondary to this initial loss, a slower and predictable first order degradation rate was observed (10%/min). Losses during both phases were accompanied by increases in Br(-) concentrations indicating that the loss of BrO(3)(-) was due to its reduction. In vivo experiments were conducted using doses of BrO(3)(-) ranging from 0.077 to 15.3mg/kg, administered intravenously (IV) or orally (gavage) to female F344 rats. The variable nature and uncertain source of background concentrations of BrO(3)(-) limited derivation of terminal half-lives, but the initial half-life was approximately 10min for all dose groups. The area under the curve (AUC) and peak concentrations (C(t=5')) were linearly related to IV dose up to 0.77mg/kg; however, disproportionate increases in the AUC and C(t=5') and a large decrease in the volume of distribution was observed when IV doses of 1.9 and 3.8mg/kg were administered. The average terminal half-life of BrO(3)(-) from oral administration was 37min, but this was influenced by background levels of BrO(3)(-) at lower doses. With oral doses, the AUC and C(max) increased linearly with dose up to 15.3mgBrO(3)(-)/kg. BrO(3)(-) appeared to be 19-25% bioavailable without an obvious dose-dependency between 0.077 and 1.9mg/kg. The urinary elimination of BrO(3)(-) and Br(-) was measured from female F344 rats for four days following administration of single doses of 8.1mgKBrO(3)/kg and for 15 days after a single dose of 5.0mgKBr/kg. BrO(3)(-) elimination was detected over the first 12h, but Br(-) elimination from BrO(3)(-) over the first 48h was 18% lower than expected based on that eliminated from an equimolar dose of Br(-) (15.5±1.6 vs. 18.8±1.2μmol/kg, respectively). The cumulative excretion of Br(-) from KBr vs. KBrO(3) was equivalent 72h after administration. The recovery of unchanged administered BrO(3)(-) in the urine ranged between 6.0 and 11.3% (creatinine corrected) on the 27th day of treatment with concentrations of KBrO(3) of 15, 60, and 400mg/L of drinking water. The recovery of total urinary bromine as Br(-)+BrO(3)(-) ranged between 61 and 88%. An increase in the fraction of the daily BrO(3)(-) dose recovered in the urine was observed at the high dose to both sexes. The deficit in total bromine recovery raises the possibility that some brominated biochemicals may be produced in vivo and more slowly metabolized and eliminated. This was supported by measurements of dose-dependent increases of total organic bromine (TOBr) that was eliminated in the urine. The role these organic by-products play in BrO(3)(-)-induced cancer remains to be established.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Oxidative stress is one of the major factors in the pathogenesis of liver disease. Quercetin is a plant-based antioxidant traditionally used as a treatment for hepatic injury, but its poor solubility affects its bioavailability. We here report the regulative effects on hepatoprotection and absorption in mice of quercetin sulfation to form quercetin-5',8-disulfonate (QS), a novel synthetic compound. Oral administration of both QS and the parent quercetin at 100, 200 and 500 mg/kg·bw prior to acute CCl4 oxidative damage in mice, effectively attenuated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) activities and hepatic malondialdehyde (MDA) levels (p < 0.05), and suppressed the CCl4-induced depletion of glutathione peroxidase (GSH-Px) and total superoxide dismutase (T-SOD). Selective 5',8-sulfation of quercetin increased the hepatoprotective effect, and its relative absorption relative to quercetin (p < 0.05) as indicated by an improved 24-hour urinary excretion and a decreased fecal excretion determined by HPLC. These results and histopathological observations collectively demonstrate that quercetin sulfation increases its hepatoprotective effects and absorption in mice, and QS has potential as a chemopreventive and chemotherapeutic agent for liver diseases.
    Molecules 12/2013; 19(1):291-305. DOI:10.3390/molecules19010291 · 2.42 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The photocatalysis of bromate (BrO3(-)) attracts much attention as BrO3(-) is a carcinogenic and genotoxic contaminant in drinking water. In this work, TiO2-graphene composite (P25-GR) photocatalyst for BrO3(-) reduction were prepared by a facile one-step hydrothermal method, which exhibited a higher capacity of BrO3(-) removal than P25 or GR did. The maximum removal of BrO3(-) was observed in the optimal conductions of 1% GR doping and at pH 6.8. Compared with that without UV, the higher decreasing of BrO3(-) on the composite indicates that BrO3(-) decomposition was predominantly contributed to photo-reduction with UV rather than adsorption. This hypothesis was supported by the decreasing of [BrO3(-)] with the synchronous increasing of [Br(-)] at nearly constant amount of total Bromine ([BrO3(-)] + [Br(-)]). Furthermore, the improvement of BrO3(-) reduction on P25-GR was observed in the treatment of a tap water. However, the efficiency of BrO3(-) removal was less than that in deionized water, probably due to the consumption of photo-generated electrons and the adsorption of natural organic matters (NOM) on graphene.
    Water Research 03/2014; 57C:1-7. DOI:10.1016/j.watres.2014.02.042 · 5.32 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Sonolytic ozonation (US/O3) is an effective way to degrade many pollutants in drinking water as the elevated mass transfer rate of ozone gas and the enhanced forming of hydroxyl radicals (OH). This work investigated the formation of bromate (BrO3(-)) from bromide (Br(-)) in sonolytic ozonation. At neutral pH, the bromate conversion rate ([BrO3(-)]/[Br(-)]0) was increased to 60% by ultrasound at continuous ozone flow (0-0.2Lmin(-1)), much higher than that without ultrasound or without bubbling. This indicates that the promoting effect of sonolysis on BrO3(-) formation is mainly due to the sonolytic decomposition of ozone and the enhancement of gas-liquid transfer. The [BrO3(-)]/[Br(-)]0 was increased with increasing pH. In addition, the reduction of HOBr/OBr(-) with ultrasound demonstrates that bromate may be inhibited as the bromide was formed with the H2O2 generation under ultrasound. This suggests the competition between bromate and bromide during the US/O3 led to the inhibition of bromate formation at high ozone flow. Therefore, our result reveals that the bromate formation under ultrasound is improved remarkably in US/O3 in quick treatment with proper ozone flow (<0.2Lmin(-1)).
    Ultrasonics Sonochemistry 06/2014; DOI:10.1016/j.ultsonch.2014.05.024 · 3.82 Impact Factor