Showing papers in "Regulatory Toxicology and Pharmacology in 2022"

TL;DR: In this article , the U.S. Food and Drug Administration (US FDA) identified dietary exposure to heavy metals as a public health concern, focusing particularly on arsenic, cadmium, lead, and mercury.

TL;DR: In this article , a 10-step read-across (RAX) framework is presented for use in cases where a threshold of toxicological concern (TTC) approach to cosmetics safety assessment is not possible.

TL;DR: In this paper , the authors present the state of the art as well as the needs for future activities, based on discussions at the workshop and further considerations, and the case of Smart Nanomaterials is used to illustrate the Safe- and Sustainable-By-Design concept and challenges for its implementation.

TL;DR: The European Partnership for Alternative Approaches to Animal Testing (EPAA) has recently held a Deep Dive Workshop to explore the use of NAMs in chemical safety assessment, the aim of which was to support regulatory decisions whilst intending to protect human health as discussed by the authors .

TL;DR: In this article , the omics data analysis framework for regulatory application (R-ODAF) is proposed to analyze raw transcriptomics data from microarray and next-generation sequencing.

TL;DR: In this article , the authors developed and applied next generation approaches to skin allergy risk assessment (SARA) that do not require new animal test data and better quantify uncertainties, and applied the SARA model within their weight of evidence NGRA framework for skin allergy to three case study materials in four consumer products.

TL;DR: In this paper , a case study with propylparaben (PP) demonstrates a 10-step read-across (RAX) framework in practice, and establishes a proof-of-concept for the value added by new approach methodologies (NAMs) in RAX for use in a next generation risk assessment (NGRA) in order to assess consumer safety after exposure to PP-containing cosmetics.

TL;DR: In this article , a mode of action-informed tiered testing, aimed at full inclusion of existing hazard data and selection of relevant biological events towards a certain adverse outcome, i.e., inhalation carcinogenicity, is introduced.

TL;DR: In 2019, the US FDA updated its interim reference level (IRL) for lead from food to 2.2 μg/day for children and 8.8 μg/dL for females of childbearing age as mentioned in this paper .

TL;DR: In this paper , the authors used the Ames test to detect the carcinogenic hazards of N-Nitrosamines (NAs) in rat and hamster liver induced S9 (80-93% versus 77-96%) and showed that the sensitivity of the Ames is high when using DMSO as a solvent.

TL;DR: In this paper , the authors used the retained doses at the various areas of the inhalation tract estimated from a computational fluid-particle dynamics (CFPD) model coupled with a simple clearance model.

TL;DR: Population-based models are now beginning to realize their potential to address long-standing data gaps in inter-and intra-species variability in human health risk assessment, such as hazard identification, exposure response assessment, and mechanistic understanding of toxicity steps of traditional risk assessments as mentioned in this paper .

TL;DR: An expert panel was convened to provide insight and guidance on per-and polyfluoroalkyl substances (PFAS) grouping for the purposes of protecting human health from drinking water exposures, and how risks to PFAS mixtures should be assessed as discussed by the authors .

TL;DR: In this article , the authors explored the possibility of grouping cobalt substances for predicting inhalation toxicity based on in vitro data using the stabilization of hypoxia-inducible factor (HIF)-1α as a read out for intracellular Co ion content.

TL;DR: The concept of maximum tolerated dose (MTD) was introduced in the seventies for carcinogenicity testing and was defined as the highest dose inducing clear toxicity, but not mortality by causes other than cancer as mentioned in this paper .

TL;DR: In this article , a workgroup comprised of scientists from government, academia, non-governmental organizations, and industry stakeholders developed a framework for waiver rationales of rodent cancer bioassays for consideration in agrochemical safety assessment.

TL;DR: In this paper , a case-by-case hypothesis-driven interpretation of bioinformatic results that leverages additional metadata rather than an alignment threshold driven interpretation is proposed. But the authors do not discuss the use of a database for toxin detection.

TL;DR: In this paper , the authors proposed to update the published DST values by expanding the size of the Local Lymph Node Assay dataset upon which they are based, whilst assigning chemical reactivity using an in-silico expert system (Derek Nexus).

TL;DR: In this paper , the adverse health effects associated with dietary cadmium exposure were identified in order to make informed decisions about the most appropriate toxicological reference value (TRV) for use in assessing dietary Cd exposure.

TL;DR: In this article , the authors systematically evaluated all of the available and relevant in vitro and in vivo data across this family of substances using an approach based around the EFSA/ECHA 2018 guidance for the identification of endocrine disruptors.

TL;DR: The carcinogenicity and developmental toxicity of unrefined mineral oil is related to its 3-7 ring polycyclic aromatic compounds (PAC) content, therefore, refining operations focus on the targeted removal PAC from mineral oil that may contain aromatics of low toxicological concern as mentioned in this paper .

TL;DR: The majority opinion of this international collaboration is that the studies striking the best balance in addressing some of these uncertainties indicate the likely central tendency of the human PFOA half-life is less than 2 years as mentioned in this paper .

TL;DR: In this paper , a screening method based on LC-QqqQ-MS was developed and validated for screening 40 substances of high concern in tattoo inks, including 5-nitro toluidine and 4-chloroaniline.

TL;DR: In this paper , the suitability of traditional animal toxicology studies designed for testing chemicals for relevance in assessing probiotic safety has been questioned, and the importance of proper manufacturing practices with regard to final product safety is also included.

TL;DR: In this paper , the Ames test was used to detect mutagenic potential of complex API-related N-nitrosamines, such as (S)-2-(((2'-(1H-tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)(nitroso)amino)-3-methylbutanoic acid (named 181−14).

TL;DR: A review of 19 Good Laboratory Practice (GLP)-compliant toxicity studies in non-human primates (NHPs) with AAV-based gene therapy products via a variety of different dose routes in the period 2017-2021 showed results ranging from no study findings different from controls, or findings considered to be non-adverse, to actual toxicity, with changes highlighting careful monitoring in the clinic as discussed by the authors .

TL;DR: In this paper , the authors showed that cobalt substances predominantly induce pre-inflammatory biomarkers, resulting in a grouping of substances either predicted to cause inflammation following inhalation, or those with a different reactivity profile (poorly reactive).

TL;DR: In this article , a database of NAMs and in vivo (human and local lymph node assay) reference data was compiled, and 41 substances highly relevant for the cosmetic industry were tested in six NAM (Direct Peptide Reactivity Assay, KeratinoSens™, human Cell Line Activation Test, U-SENS™, SENS-IS, Peroxidase Peptides Reactivities Assay).

TL;DR: In this paper , the potential of nine cobalt substances to cause genotoxicity and oxidative stress using the ToxTracker assay, with an extension to measure biomarkers of hypoxia.

TL;DR: In this article , the authors proposed twelve criteria to assess the uncertainty associated with structural alerts, allowing for an assessment of confidence, based on the stated purpose, description of the chemistry, toxicology and mechanism, performance and coverage, as well as corroborating and supporting evidence of the alert.