The time to reach the maximum plasma nicotine concentration was longer for PNCIT compared to CC, suggesting that nicotine delivered from Napabucasin PNCIT was absorbed primarily in the upper airway, not in the pulmonary sites as cigarette smoking. The relative bioavailability of nicotine for PNCIT compared to CC was 0.92 +/- 0.32, indicating similar nicotine bioavailability for both forms. The difference in the elimination half-lives between the test products was not significant, suggesting that the elimination of nicotine from blood is not affected significantly by the difference in the nicotine absorption sites. (C) 2013 Elsevier Inc. All rights reserved.”
“There are pitfalls associated with exposure-response modeling

of human epidemiological data based on rate ratios (RRs). Exposure-response modeling is best based on individual data, when

available, rather than being based on summary results of that data such as categorical RRs. Because the data for the controls (or the lowest exposure interval if there are not enough controls) are random and not known with certainty a priori, any exposure-response model fit to RRs should estimate the intercept rather than fixing it equal to one. Evaluation of a model’s goodness-of-fit to the individual data should not be based on the assumption that summary RRs describe the true underlying exposure-response relationship. These pitfalls are illustrated by Monte Carlo simulation

examples with known underlying models. That these pitfalls are a practical concern is illustrated by the need for U.S. EPA to reconsider SHP099 its most recent evaluation of ethylene oxide. If they had avoided these pitfalls, their exposure-response modeling selleck products would have been in better agreement with the log-linear model fit to the individual data. (C) 2013 The Authors. Published by Elsevier Inc. All rights reserved.”
“In typical rodent pesticide feeding studies of 4 up to 104 weeks, animals are offered the pesticide at constant concentrations in the feed. Throughout the entire study duration of up to 104 weeks, the daily feed consumption per animal remains nearly constant. This results in decreasing doses per kg bodyweight from the first day of treatment onwards as the bodyweight increases. Recently, we have identified this dose decrement as the major cause for lower No Observed Effect Levels (NOAEL, expressed as mg/kg bodyweight) in longer-term studies compared to shorter-term studies, rather than the exposure duration itself. In the current evaluation we investigated the nature of the dose decrement in more detail by using male and female bodyweight and feed consumption data from 118 feeding studies of three rat strains to calculate dose development over time. In male rats, after a steep initial dose decrement, the mean dose at week 7 of treatment is on average half of the initial dose and after 29 weeks one third of the initial dose.