Rebooting the generally recognized as safe (GRAS) approach for food additive safety in the US.

The US Food and Drug Administration (FDA) has premarket review authority over food additives, but a food manufacturer may, according to the legislation, intentionally add a substance to human food or animal food without their premarket review or approval if the substance is generally recognized, among qualified experts, to be safe under the conditions of its intended use. Generally recognized as safe (GRAS) implies that the current scientific community agrees on the adequacy of how data is generated. This system has come under public pressure because of doubts as to its efficiency and the FDA's recent GRAS rule is part of the response.

Computational approaches to chemical hazard assessment.

Computational prediction of toxicity has reached new heights as a result of decades of growth in the magnitude and diversity of biological data. Public packages for statistics and machine learning make model creation faster. New theory in machine learning and cheminformatics enables integration of chemical structure, toxicogenomics, simulated and physical data in the prediction of chemical health hazards, and other toxicological information.

The Emergence of Systematic Review in Toxicology.

The Evidence-based Toxicology Collaboration hosted a workshop on "The Emergence of Systematic Review and Related Evidence-based Approaches in Toxicology," on November 21, 2014 in Baltimore, Maryland. The workshop featured speakers from agencies and organizations applying systematic review approaches to questions in toxicology, speakers with experience in conducting systematic reviews in medicine and healthcare, and stakeholders in industry, government, academia, and non-governmental organizations. Based on the workshop presentations and discussion, here we address the state of systematic review methods in toxicology, historical antecedents in both medicine and toxicology, challenges to the translation of systematic review from medicine to toxicology, and thoughts on the way forward.

Guidance on assessing the methodological and reporting quality of toxicologically relevant studies: A scoping review.

Assessments of methodological and reporting quality are critical to adequately judging the credibility of a study's conclusions and to gauging its potential reproducibility. To aid those seeking to assess the methodological or reporting quality of studies relevant to toxicology, we conducted a scoping review of the available guidance with respect to four types of studies: in vivo and in vitro, (quantitative) structure-activity relationships ([Q]SARs), physico-chemical, and human observational studies. Our aims were to identify the available guidance in this diverse literature, briefly summarize each document, and distill the common elements of these documents for each study type.

Proposal for international recognition, support and cooperation with the Internet clearinghouse on the Three Rs (Altweb).

This presentation will focus on the establishment and current international scope of Altweb, the clearinghouse of resources and information about the Three Rs. The need for an international central reference point was established by the European Centre for the Validation of Alternative Methods workshop number 25, which was followed by the development and implementation of Altweb through a Project Team. The growth of the Project Team to include representatives from several European countries and Canada, in addition to widespread support in the USA, and the Project Team's role in shaping this important resource will be discussed, as well as the role Altweb will continue to play in spurring the development of information resources on the Three Rs at an international level.

Characterization of a primary hepatocyte culture system for toxicological studies.

An hepatocyte culture system was developed for potential use in toxicological studies in vitro. Rat hepatocytes were isolated by two-step collagenase perfusion and cultured on Vitrogen-coated Permanox dishes in a modified Chee's medium containing 1 microM dexamethasone and 1% dimethylsulfoxide. The cells remained highly viable for at least 10 d as determined by lactate dehydrogenase release and total protein levels.

The role of mechanistic toxicology in test method validation.

There are two approaches to in vitro toxicity test validation, phenomenological and mechanistic. The phenomenological approach uses correlative mathematical techniques, with no regard to the identification of mechanistic relationships, to relate in vitro measurements of toxicity to in vivo toxicological responses in order to establish the validity of the methods under consideration. This approach has three major limitations: (1) success or failure of a particular test will depend critically on the selection of test chemicals; (2) the reason why a chemical fails in a particular test is unknown; (3) without additional information there is no rational basis for extrapolation to new cases lying outside the domain of validation.