Regulatory toxicology and pharmacology : RTP
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Regul. Toxicol. Pharmacol. · Feb 2019
ReviewLegal aspects of zebrafish neuropharmacology and neurotoxicology research.
Despite the growing emphasis on translational neuropharmacology and drug discovery research, the legality underlying these fields are seldom considered. The zebrafish (Danio rerio) is an increasingly utilized model organism in neuropharmacology and neurotoxicology. ⋯ Here, we discuss a wide range of regulatory topics relevant to zebrafish research, such as the bioethics of experimentation (including studies of stress and pain), welfare protection laws, the recent advances in CNS drug discovery, and specific legal aspects of controlled substance research in this aquatic species. The conceptualization and understanding of the zebrafish welfare and its promise as a model in toxicology can also potentially shape environmental protection practices and inform policy making.
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Regul. Toxicol. Pharmacol. · Feb 2019
Assessment of the approved Risk Evaluation and Mitigation Strategy programs for New Drug Applications and Biologics Licensing Applications.
The Food and Drug Amendments Act of 2007, (FDAAA), granted the United States Food and Drug Administration to require drug manufacturers to develop a Risk Evaluation and Mitigation Strategy, (REMS). Implementation of the FDAAA required drug manufacturers to utilize risk minimization strategies beyond routine labeling for benefit-risk profiles of prescription drugs. The first full year of FDAAA implementation, 2008, through 2016, was reviewed to assess presence of differences in REMS requirements in Center for Drug Evaluation and Research (CDER) New Drug Applications, (NDAs), and Biologics License Applications, (BLAs). The risks present in the current unreleased approved REMS were reviewed to determine any difference in FDA requirements for safety risks identified in the NDA and BLA REMS programs.
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Regul. Toxicol. Pharmacol. · Aug 2018
Comparative StudyInvestigation and comparison of the transfer of TSNA from tobacco to cigarette mainstream smoke and to the aerosol of a heated tobacco product, THS2.2.
Tobacco-specific nitrosamines (TSNA) levels in tobacco cut filler and cigarette smoke were measured in more than 1000 commercially available cigarettes sampled between 2008 and 2014. Relative contributions to their transfer from tobacco to the mainstream smoke in terms of direct transfer by distillation, pyrorelease, and pyrosynthesis were evaluated on the basis of the comparison with the transfer of nicotine from tobacco to smoke. ⋯ In the case of the Tobacco Heating System 2.2, the transfer of nicotine from tobacco to the aerosol was similar to that observed for cigarettes, while the % transfer of TSNAs from tobacco to THS 2.2 aerosol was 2-3 times lower than in cigarettes. This difference is due to the fact that the tobacco is heated instead of burnt resulting in a lower direct transfer by distillation and a lower if any contribution of pyrosynthesis or pyrorelease.
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Regul. Toxicol. Pharmacol. · Jul 2018
Randomized Controlled Trial Comparative StudyAssessment of the exposure to harmful and potentially harmful constituents in healthy Japanese smokers using a novel tobacco vapor product compared with conventional cigarettes and smoking abstinence.
The objectives of this clinical study were to demonstrate a reduction in exposure to selected harmful and potentially harmful constituents (HPHCs), and to assess product use behavior, in Japanese healthy adult smokers who switched to a novel tobacco vapor product (NTV). 60 smokers were randomly assigned for 5 days to either (a) a group who switched to an NTV (n = 20), (b) a group who continued to smoke their own brand of conventional cigarettes (CC, n = 20) or (c) a smoking abstinence group (SA, n = 20). Fifteen biomarkers of exposure (BoEs) to 14 HPHCs and pyrene were measured at baseline, day 3 and 5. Product use behavior was assessed by measuring product consumption, nicotine uptake and puffing topography. ⋯ Additionally, nicotine uptake in the NTV group was approximately half that observed in the CC group. BoE values were significantly reduced in the NTV group as compared to those in the CC group. Significantly, the magnitude of the reduction in exposure to HPHCs observed in the NTV group (49-94%) was close to that observed for the SA group (39-95%).
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Regul. Toxicol. Pharmacol. · Jul 2018
Canadian, European and United States new drug approval times now relatively similar.
The objectives of this analysis were to assess whether consistency in Health Canada's (HC's) approval times identified in 2011 has been sustained and to compare HC's approval times with those of the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). Between 2002 and 2016, 460 new drugs were approved by at least one of the agencies: 351 (76.3%), 319 (69.3%) and 392 (85.2%) by HC, the EMA and the FDA, respectively - all three approved 252 (54.8%). ⋯ Almost 80% of the drugs approved by all three agencies were submitted to HC later than to the other two agencies, which led to a median delay of a year between the agency first giving approval (FDA or EMA) and HC's approval. Rates of drugs withdrawn for safety reasons were 1.4% in Canada, 0.9% in Europe and 0.8% in the United States.