Assessment of consumer exposure to boron in cleaning products: a case study of Canada.

Boron is an essential mineral for plants, and as such, is a normal dietary constituent for humans. Humans may be naturally exposed to boron through food and drinking water, or via anthropogenic sources such as consumer products. The World Health Organisation established an acceptable safe range of population mean intakes for boron of 1-13 mg/day. Most studies of dietary boron intake show a range of 1-2 mg/day. Consumer products have been estimated to contribute a geometric mean daily intake of 0.1 mg to total boron exposure; however, there are few published surveys of consumer exposure to boron from use of cleaning products. The Government of Canada published a draft screening assessment report of boric acid, its salts and precursors that included estimates of consumer exposure to boron found as ingredients in consumer products. The manufacturers of consumer cleaning products conducted a survey of boron content of current products and estimated exposure using the publicly available exposure tool ConsExpo Web. Dermal exposures to boron during cleaning product use were estimated to result in annual internal exposures ranging from ≪0.001 to 0.36 µg/kg bw/day based on dermal absorption of 0.5%. Using a conservative point of departure for hazard assessment (2,900 µg boron/kg bw/day), estimated margins of exposure for dermal exposures to boron from cleaning product use range from 8,056 to >1,000,000. This work demonstrates that exposure to boron from cleaning product use is very low and essentially insignificant when compared to other (e.g. dietary) sources of boron intake by Canadian consumers.

Description and evaluation of a peracetic acid air sampling and analysis method.

Peracetic acid (PAA) is a corrosive chemical with a pungent odor, which is extensively used in occupational settings and causes various health hazards in exposed workers. Currently, there is no US government agency recommended method that could be applied universally for the sampling and analysis of PAA. Legacy methods for determining airborne PAA vapor levels frequently suffered from cross-reactivity with other chemicals, particularly hydrogen peroxide (H2O2). Therefore, to remove the confounding factor of cross-reactivity, a new viable, sensitive method was developed for assessment of PAA exposure levels, based on the differential reaction kinetics of PAA with methyl p-tolylsulfide (MTS), relative to H2O2, to preferentially derive methyl p-tolysulfoxide (MTSO). By quantifying MTSO concentration produced in the liquid capture solution from an air sampler, using an internal standard, and utilizing the reaction stoichiometry of PAA and MTS, the original airborne concentration of PAA is determined. After refining this liquid trap high-performance liquid chromatography (HPLC) method in the laboratory, it was tested in five workplace settings where PAA products were used. PAA levels ranged from the detection limit of 0.013 parts per million (ppm) to 0.4 ppm. The results indicate a viable and potentially dependable method to assess the concentrations of PAA vapors under occupational exposure scenarios, though only a small number of field measurements were taken while field testing this method. However, the low limit of detection and precision offered by this method makes it a strong candidate for further testing and validation to expand the uses of this liquid trap HPLC method.

Metformin Scavenges Methylglyoxal To Form a Novel Imidazolinone Metabolite in Humans.

Methylglyoxal (MG) is a highly reactive dicarbonyl compound involved in the formation of advanced glycation endproducts (AGE). Levels of MG are elevated in patients with type-2 diabetes mellitus (T2DM), and AGE have been implicated in the progression of diabetic complications. The antihyperglycemic drug metformin (MF) has been suggested to be a scavenger of MG. The present work examined and characterized unequivocally the resulting scavenged product from the metformin-MG reaction. The primary product was characterized by (1)H, (13)C, 2D-HSQC, and HMBC NMR and tandem mass spectrometry. X-ray diffraction analysis determined the structure of the metformin and MG-derived imidazolinone compound as (E)-1,1-dimethyl-2-(5-methyl-4-oxo-4,5-dihydro-1H-imidazol-2-yl)guanidine (IMZ). A LC-MS/MS multiple reaction monitoring method was developed to detect and quantify the presence of IMZ in metformin-treated T2DM patients. Urine from >90 MF-treated T2DM patients was analyzed, with increased levels of MF directly correlating with elevations in IMZ. Urinary MF was detected in the range of 0.17 µM to 23.0 mM, and simultaneous measurement of IMZ concentrations were in the range of 18.8 nM to 4.3 µM. Since plasma concentrations of MG range from 40 nM to 4.5 µM, the level of IMZ production may be of therapeutic significance. Thus, in addition to lowering hepatic gluconeogenesis, metformin also scavenges the highly reactive MG in vivo, thereby reducing potentially detrimental MG protein adducts, with subsequent reductions in diabetic complications.

Site specific modification of the human plasma proteome by methylglyoxal.

Increasing evidence identifies dicarbonyl stress from reactive glucose metabolites, such as methylglyoxal (MG), as a major pathogenic link between hyperglycemia and complications of diabetes. MG covalently modifies arginine residues, yet the site specificity of this modification has not been thoroughly investigated. Sites of MG adduction in the plasma proteome were identified using LC-MS/MS analysis in vitro following incubation of plasma proteins with MG. Treatment of plasma proteins with MG yielded 14 putative MG hotspots from five plasma proteins (albumin [nine hotspots], serotransferrin, haptoglobin [2 hotspots], hemopexin, and Ig lambda-2 chain C regions). The search results revealed two versions of MG-arginine modification, dihydroxyimidazolidine (R+72) and hydroimidazolone (R+54) adducts. One of the sites identified was R257 in human serum albumin, which is a critical residue located in drug binding site I. This site was validated as a target for MG modification by a fluorescent probe displacement assay, which revealed significant drug dissociation at 300 µM MG from a prodan-HSA complex (75 µM). Moreover, twelve human plasma samples (six male, six female, with two type 2 diabetic subjects from both genders) were analyzed using multiple reaction monitoring (MRM) tandem mass spectrometry and revealed the presence of the MG-modified albumin R257 peptide. These data provide insights into the nature of the site-specificity of MG modification of arginine, which may be useful for therapeutic treatments that aim to prevent MG-mediated adverse responses in patients.