In 2009, the 4th meeting of the Conference of the Parties to the Stockholm Convention added PFOS, its salts and POSF into Annex B to restrict the production and usage of PFOS-related compounds, with exemptions for specific uses 11. The 3 M Company phased out PFOS production in 2002 due to its environmental persistence and potential toxicity.
They were also suspected to affect adult thyroid hormone function and increase certain carcinogenic activities 9, 10. The adverse effects of PFAAs on humans, such as osteoarthritis and a delay of puberty, have been proposed 7, 8. PFAAs contamination was not only found around point sources, such as fluorochemical facilities 3, but also detected in remote areas, such as the Tibetan Plateau 4 and the Arctic 5, 6, due to their high historic production and continuous release.
The 3 M Company was the main PFOS producer in history and manufactured approximately 3600 tonnes per year of POSF before 2002 2. From 1970 to 2002, approximately 96,000 tonnes of perfluorooctane sulfonyl fluoride (POSF), a perfluorooctanesulfonate (PFOS) precursor, were produced, and approximately 450–2700 tonnes of PFOS entered wastewater streams 2. Perfluoroalkyl acids (PFAAs) are a group of highly stable man-made compounds that are used in surfactants, fluorinated polymers, and fire-resistant foams because of their unique thermal and acid resistance, as well as their hydro- and lipophobic properties 1. The half-lives estimated by annual decline rates in the present study were the shortest values ever reported, and the intrinsic half-lives might even shorter due to the high levels of ongoing exposure to PFAAs. The half-lives estimated by the limited clearance route information could be considered as the upper limits for PFAAs, however, the huge difference between two estimated approaches indicated that there were other important elimination pathways of PFAAs other than renal clearance in human. The geometric mean and median value for PFHxS, PFOA, and PFOS were 14.7 and 11.7, 4.1 and 4.0, 32.6 and 21.6 years, respectively, by the daily clearance rates, and they were 3.6, 1.7, and 1.9 years estimated by annual decline rates. The half-lives of PFAAs in workers were estimated by daily clearance rates and annual decline rates of PFAAs in serum by a first-order model. High levels of perfluorohexane sulfonate (PFHxS), perfluorooctanoic acid (PFOA), and perfluorooctanesulfonate (PFOS) were detected in serum with median concentrations of 764, 427, and 1725 ng mL −1, respectively. While all six SGLT2 inhibitors were significantly effective in increasing urinary glucose excretion and reducing hyperglycemia, our findings suggest that variation in the quality of daily blood glucose control associated with duration and onset of pharmacologic effects of each SGLT2 inhibitor might cause slight differences in rates of improvement in type 2 diabetes.Paired serum and urine samples were collected from workers in a fluorochemical plant from 2008 to 2012 (n = 302) to investigate the level, temporal trends, and half-lives of PFAAs in workers of a fluorochemical plant. Duration and onset of the pharmacologic effects seemed to be closely correlated with the pharmacokinetic properties of each SGLT2 inhibitor, particularly with respect to high distribution and long retention in the target organ, the kidney. In addition, ipragliflozin and luseogliflozin exhibited superiority over the others with respect to fast onset of pharmacological effect. Long-acting SGLT2 inhibitors exerted an antihyperglycemic effect with lower variability of blood glucose level via a long-lasting increase in urinary glucose excretion. Based on findings in normal and diabetic mice, the six drugs were classified into two categories, long-acting: ipragliflozin and dapagliflozin, and intermediate-acting: tofogliflozin, canagliflozin, empagliflozin, and luseogliflozin. In the present study, the pharmacokinetic, pharmacodynamic, and pharmacologic properties of all six SGLT2 inhibitors commercially available in Japan were investigated and compared. The sodium-glucose cotransporter (SGLT) 2 offer a novel approach to treating type 2 diabetes by reducing hyperglycaemia via increased urinary glucose excretion.
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