Regulatory toxicology and pharmacology : RTP
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Regul. Toxicol. Pharmacol. · Aug 2014
Developing scientific confidence in HTS-derived prediction models: lessons learned from an endocrine case study.
High throughput (HTS) and high content (HCS) screening methods show great promise in changing how hazard and risk assessments are undertaken, but scientific confidence in such methods and associated prediction models needs to be established prior to regulatory use. Using a case study of HTS-derived models for predicting in vivo androgen (A), estrogen (E), thyroid (T) and steroidogenesis (S) endpoints in endocrine screening assays, we compare classification (fitting) models to cross validation (prediction) models. The more robust cross validation models (based on a set of endocrine ToxCast™ assays and guideline in vivo endocrine screening studies) have balanced accuracies from 79% to 85% for A and E, but only 23% to 50% for T and S. ⋯ However, continued research is needed to expand the domain of applicability and to develop more robust HTS/HCS-based prediction models prior to their use in other regulatory applications. Based on the lessons learned, we propose a framework for documenting scientific confidence in HTS assays and the prediction models derived therefrom. The documentation, transparency and the scientific rigor involved in addressing the elements in the proposed Scientific Confidence Framework could aid in discussions and decisions about the prediction accuracy needed for different applications.
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Regul. Toxicol. Pharmacol. · Aug 2014
Randomized Controlled TrialExposure evaluation of adult male Japanese smokers switched to a heated cigarette in a controlled clinical setting.
The objective of this clinical study was to investigate changes in levels of biomarkers of exposure (BOEs) in healthy Japanese male smokers who switched to a prototype heated cigarette (HC). This was a controlled, semi-randomized, open-label, residential study conducted in Japan. A total of 70 healthy Japanese male smokers were enrolled. ⋯ Levels of BOEs for ten selected cigarette smoke constituents (nicotine, carbon monoxide (CO), benzene, 1,3-butadiene, acrolein, hydrogen cyanide, crotonaldehyde, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone [NNK], pyrene, 4-aminobiphenyl), and urine mutagenicity were measured at several time points during the study period. At the end of the study period, except for blood carboxyhemoglobin, levels of BOEs for the other nine constituents and urine mutagenicity were significantly lower in the HC group compared to the CC10 group. These results suggest that exposure to most cigarette smoke constituents, except CO, can be reduced by switching from CC10 to HC.
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Regul. Toxicol. Pharmacol. · Aug 2014
Cannabis, pesticides and conflicting laws: the dilemma for legalized States and implications for public health.
State laws on the legalization of medical and recreational cannabis are rapidly evolving. Similar to other crops, cannabis is susceptible to multiple pests during cultivation. Growers have an economic incentive to produce large yields and high quality plants, and may resort to pesticides to achieve these outcomes. ⋯ The absence of approved products for cannabis may result in consumer exposures to otherwise more hazardous pesticides or higher residue levels. While many legal and scientific hurdles exist to register conventional pesticides for use on cannabis, legalized States have explored other opportunities to leverage the present regulatory infrastructure. Stakeholder engagement and outreach to the cannabis industry from credible sources could mitigate pesticide misuse and harm.