Showing papers in "Regulatory Toxicology and Pharmacology in 2013"

TL;DR: This review deals with three categories of active substances for disinfectant products, their modes of action (MOA), and how MOA can help predict propensity for resistance in microorganisms.

TL;DR: The current status of various regulatory frameworks of the European Union with regard to nanomaterials is described, and major issues relevant for regulation of nanommaterials are discussed.

TL;DR: An overview on current regulations of chemicals and the requirements for animal tests in environmental hazard and risk assessment is provided and the potential areas for alternative approaches to animal tests using vertebrates in environmental toxicology are highlighted.

TL;DR: The procedures presented here for structure-based assessment are considered appropriate for regulatory submissions in the scope of ICH M7 and a rule-based expert system complemented by either expert knowledge or a second (Q)SAR model is appropriate.

TL;DR: There are still important gaps in the knowledge required to assess thujone toxicity, the most important ones being human dose-concentration-effect relationships including the elucidation of bioavailability, and the actual toxicological consequences of potential pharmacogenetic variations and environmental factors.

TL;DR: The results showed that under-studied compounds such as levothyroxine and montelukast sodium received the highest scores, suggesting the importance of removal mechanisms in influencing the ranking, and the need for future environmental research to include other less-studies but potentially harmful pharmaceutical compounds.

TL;DR: The authors have identified opportunities to maximize the predictivity of this information to humans while reducing animal use in four key areas; accelerating the uptake of in vitro methods, incorporating the latest science into safety pharmacology assessments, and optimizing rodent study design in biological development.

TL;DR: The focus of this present paper is to describe some of the technical and practical considerations when applying read-across under REACH.

TL;DR: A number of mammalian RNAi studies support the concept that a large margin of safety will exist for any small fraction of RNAs that might be absorbed following consumption of foods from biotechnology-derived plants that employ RNA-mediated gene regulation, and food and feed derived from these crops utilizing RNA-based mechanisms is expected to be as safe as food andFeed derived through conventional plant breeding.

TL;DR: Mitochondrion-toxic agents induced via these mechanisms include cardiomyopathy, myocarditis, coronary heart disease, arrhythmias, heart failure, or Takotsubo syndrome, andontinuation of the cardiotoxic agent results in complete recovery in the majority of the cases.

TL;DR: Given that reverse causation is taken account of, the model adequately describes the decline in excess risk, however, estimates of H may be biased by factors including misclassification of smoking status.

TL;DR: The existing information does not support the hypothesis that exposure to DDT/DDE increases the risk of breast cancer in humans, and a meta-analysis from 2004 found no association between dichlorodiphenyldichloroethylene (DDE) and breast cancer.

TL;DR: The lead contents of different kinds of lipsticks were determined by solid sampling high resolution continuum source electrothermal atomic absorption spectrometry (SS-HR-CS ET AAS) and the results were compared with those obtained after microwave-assisted acid digestion and there was no significant difference between the lead concentrations found by the two techniques.

TL;DR: An inventory of in silico screening tools to identify substance properties of concern under the European chemicals' legislation REACH is presented to support the selection and implementation of appropriate tools as building blocks within integrated testing strategies (ITS).

TL;DR: How the fundamental principles governing hormonal effects - affinity, efficacy, potency, and mass action - dictate the existence of thresholds and why these principles also define the potential that exogenous chemicals might have to interfere with normal endocrine functioning are highlighted.

TL;DR: This work aims to improve the link between the risk management and risk assessment strategies, with the identification of those fish and seafood species, that, when regularly consumed, could determine or prevent potential Hg(TOT)/MeHg overintakes in sensitive groups.

TL;DR: Although mechanistic models can be used to a certain degree under well-defined conditions, at the present, the in silico models are not sufficiently accurate for broad application to predict skin sensitization potentials.

TL;DR: Information on 151 studies has been used to develop an alert/warning system for BWL in short term toxicity studies and data analysis supports BWL limits for short term dosing of 10% for rat and dog and 6% for non-human primates (NHPs).

TL;DR: Switchers were consistently found to have a lower risk than continuers, with relative risks varying from 0.35 to 0.61, and a similar risk to quitters, consistent with a recent review which found no increased risk of cancer or heart disease from snus use.

TL;DR: Investigation of surface oxide characteristics and extent of nickel release in two thoroughly characterized micron-sized nickel metal powders and a nickel oxide bulk powder when immersed in two different synthetic fluids shows significantly more nickel released compared to the NiO powder compared to differences in surface properties.

TL;DR: A follow up activity was agreed upon to explore an example of an Integrated Testing Strategy for skin sensitisation hazard identification purposes in the context of REACH submissions.

TL;DR: In this paper, the authors present a framework for validation of high throughput and high content (HT/HC) methods in the field of toxicogenomics, bioinformatics, and computational toxicology to improve both the efficiency and effectiveness of toxicity evaluations and risk assessments.

TL;DR: Primary considerations for the nonclinical safety evaluation of ADCs are presented and strategies for the evaluation of the entire ADC or the various individual components (i.e., antibody, linker or the cytotoxin) are included.

TL;DR: Regulatory exposure limits for chlorpyrifos, which are based on cholinesterase inhibition, are sufficient to protect against potential endocrine alterations.

TL;DR: BAK induced very low cytotoxicity in the cultured ocular cell lines at concentrations of 0.002% or lower, and the concentration-dependency confirmed that the CVS score is useful for expressing drug cytot toxicity in a simple and comprehensive manner.

TL;DR: Though the results suggest some benefits of smoking reduction, more evidence is needed, the evidence has various weaknesses; few studies, few cases in reducers in some studies, limited dose-response data, incomplete adjustment for baseline consumption, questionable accuracy of the lifetime smoking history data in case-control studies, and bias in cohort studies if reducers are likelier than non-reducers to quit during follow-up.

TL;DR: The approach mirrors the animal data quality considerations set out by Klimisch et al., in order that human data quality can be addressed in a complementary manner and to help facilitate transparent (and repeatable) weight of evidence comparisons.

TL;DR: Results show that β-caryophyllene oxide, although absorbed through cell membranes and in spite of its potentially reactive chemical structure, is devoid of genotoxic effects, inducing neither point mutations nor chromosomal damages.

TL;DR: The goal of the WHO Guidance and the current paper is to increase regulatory acceptance of complex biologically descriptive pharmacokinetic (or toxicokinetic) models, such as PBPK models, by facilitating communication and successful interaction between modelers and risk assessors.

TL;DR: Data from 108 diverse synthetic routes from 13 companies confirm that many "alerting" or mutagenic chemicals are in structural classes with lower carcinogenic potency than those used to derive the TTC, demonstrating that such SAR analysis to "flag" potential mutagens is conservative.