1 mg and glucosuria was observed at doses >= 0.3 mg and corroborated by UGD. The NOEL was therefore 0.1 mg for glucosuria. For setting the new OEL, no UFs were required. Dividing the POD by 10 m(3) (the volume of air an adult inhales in a workday), the resulting OEL was 0.01 mg/m(3). In conclusion, low-dose clinical pharmacodynamic and pharmacokinetic data can

allow the OEL to be adjusted to the highest safe level. (C) 2013 Elsevier Inc. All rights reserved.”
“Drinking water quality standard (DWQS) criteria for chemicals for which there is a threshold for toxicity are derived by allocating a fraction of tolerable daily intake (TDI) to exposure from drinking water. We conducted physiologically based pharmacokinetic model simulations for chloroform and have proposed an equation for total oral-equivalent potential Selleckchem Ralimetinib intake via three routes (oral ingestion, inhalation, and dermal exposures), the biologically Vactosertib effective doses of which were converted to oral-equivalent potential intakes. The probability distributions of total oral-equivalent potential intake in Japanese people were estimated by Monte Carlo simulations. Even when the chloroform concentration in drinking water

equaled the current DWQS criterion, there was sufficient margin between the intake and the TDI: the probability that the intake exceeded TDI was below 0.1%. If a criterion that the 95th percentile estimate equals the TDI is regarded as both providing protection to highly exposed persons and leaving a reasonable margin of exposure relative to the TDI, then the chloroform drinking water criterion could be a concentration of 0.11 mg/L. This implies a daily intake equal to 34% of the TDI allocated to the oral intake (2 L/d) of drinking water for typical adults. For the highly exposed persons, until inhalation exposure via evaporation from water contributed 53% of the total intake, whereas dermal absorption contributed only 3%. (C) 2013 Elsevier Inc. All rights reserved.”
“The US Food and Drug Administration (FDA) Biomarker Qualification Review Team presents its perspective on the recent qualification of cardiac

troponins for use in nonclinical safety assessment studies. The goal of this manuscript is to provide greater transparency into the qualification process and factors that were considered in reaching a regulatory decision. This manuscript includes an overview of the data that were submitted and a discussion of the strengths and shortcomings of these data supporting the qualification decision. The cardiac troponin submission is the first literature-based biomarker application to be reviewed by the FDA and insights gained from this experience may aid future submissions and help streamline the characterization and qualification of future biomarkers. Published by Elsevier Inc.”
“In this study, a method was applied to evaluate pressor mechanisms through compound-protein interactions.