A5021821151- Effects and risks of endocrine disrupting chemicals
- Animal testing and alternatives
- Computational Drug Discovery Methods
- Carcinogens and Genotoxicity Assessment
- Genetically Modified Organisms Research
- Chemistry and Chemical Engineering
- Chemical Safety and Risk Management
- Environmental Toxicology and Ecotoxicology
- Risk and Safety Analysis
- Toxic Organic Pollutants Impact
- Pesticide Exposure and Toxicity
- Health, Environment, Cognitive Aging
- Immunotoxicology and immune responses
- Pesticide and Herbicide Environmental Studies
- Gene expression and cancer classification
- Agricultural safety and regulations
- Risk Perception and Management
- Flame retardant materials and properties
- Metabolomics and Mass Spectrometry Studies
- Health Systems, Economic Evaluations, Quality of Life
- Microplastics and Plastic Pollution
- Pharmaceutical Quality and Counterfeiting
- Biotechnology and Related Fields
- Insect Resistance and Genetics
- Radiation Dose and Imaging
Health Canada
2015-2025
AstraZeneca (United Kingdom)
2019
Novartis (Switzerland)
2019
PPG Industries (United States)
2019
ABS Consulting (United States)
2019
Government of Canada
2019
Systematic consideration of scientific support is a critical element in developing and, ultimately, using adverse outcome pathways (AOPs) for various regulatory applications. Though weight evidence (WoE) analysis has been proposed as basis assessment the maturity and level confidence an AOP, methodologies tools are still being formalized. The Organization Economic Co-operation Development (OECD) Users' Handbook Supplement to Guidance Document Developing Assessing AOPs (OECD 2014a; hereafter...
Abstract Use of high-throughput, in vitro bioactivity data setting a point-of-departure (POD) has the potential to accelerate pace human health safety evaluation by informing screening-level assessments. The primary objective this work was compare PODs based on high-throughput predictions bioactivity, exposure predictions, and traditional hazard information for 448 chemicals. derived from new approach methodologies (NAMs) were obtained comparison using 50th (PODNAM, 50) 95th 95) percentile...
There is increasing interest in the use of quantitative transcriptomic data to determine benchmark dose (BMD) and estimate a point departure (POD) for human health risk assessment. Although studies have shown that transcriptional PODs correlate with those derived from apical endpoint changes, there no consensus on process used derive POD. Specifically, subsets informative genes produce BMDs best approximate doses at which adverse effects occur not been defined. To way select predictive...
Next generation risk assessment (NGRA) is an exposure-led, hypothesis-driven approach that has the potential to support animal-free safety decision-making. However, significant effort needed develop and test in vitro silico (computational) approaches underpin NGRA enable confident application a regulatory context. A workshop was held Montreal 2019 discuss where needs be focussed agree on steps ensure decisions made cosmetic ingredients are robust protective. Workshop participants explored...
Use of molecular data in human and ecological health risk assessments industrial chemicals agrochemicals has been anticipated by the scientific community for many years; however, these are rarely used assessment. Here, a logic framework is proposed to explore feasibility future development transcriptomic methods refine replace current apical endpoint-based regulatory toxicity testing paradigm. Four foundational principles outlined discussed that would need be accepted stakeholders prior this...
The growing number of chemicals in the current consumer and industrial markets presents a major challenge for regulatory programs faced with need to assess potential risks they pose human ecological health. increasing demand hazard risk assessment currently exceeds capacity produce toxicity data necessary decision making, applied is commonly generated using traditional approaches animal models that have limited context terms relevance. This scenario provides opportunity implement novel, more...
In silico toxicology (IST) approaches to rapidly assess chemical hazard, and usage of such methods is increasing in all applications but especially for regulatory submissions, as assessing chemicals under REACH well the ICH M7 guideline drug impurities. There are a number obstacles performing an IST assessment, including uncertainty how assessment associated expert review should be performed or what fit purpose, lack confidence that results will accepted by colleagues, collaborators...
The replacement of regulated brominated flame retardants and plasticizers with organophosphate esters (OPEs) has led to their pervasive presence in the environment biological matrices. Further, there is evidence that exposure some these chemicals associated reproductive toxicity. Using a high-content imaging approach, we assessed effects 9 OPEs on cells related function: KGN human granulosa cells, MA-10 mouse Leydig C18-4 spermatogonial cells. were compared those 2,2',4,4'-tetrabromodiphenyl...
Computational toxicology models have been successfully implemented to prioritize and screen chemicals. There are numerous in silico (quantitative) structure–activity relationship ([Q]SAR) for the prediction of a range human-relevant toxicological endpoints, but given endpoint chemical, not all predictions identical due differences their training sets, algorithms, methodology. This poses an issue high-throughput screening large chemical inventory as it necessitates several cover diverse...
Risk assessments are increasingly reliant on information from in vitro assays. The micronucleus test (MNvit) is a genotoxicity that detects chromosomal abnormalities, including chromosome breakage (clastogenicity) and/or whole loss (aneugenicity). In this study, MNvit datasets for 292 chemicals, generated by the US EPA's ToxCast program, were evaluated using decision tree-based pipeline hazard identification. Chemicals tested with 19 concentrations (n = 1) up to 200 µM, presence and absence...
Use of new approach methods (NAMs), including high-throughput, in vitro bioactivity data, setting a point-of-departure (POD) will accelerate the pace human health hazard assessments. Combining and exposure predictions into bioactivity: Exposure ratio (BER) for use risk-based prioritization utilizing NAM-based flags to indicate potential hazards interest further prediction or mechanism-based screening together comprise prospective management substances with limited traditional toxicity...
The European Partnership for Alternative Approaches to Animal Testing (EPAA) held the "New Approach Methodologies (NAMs) User Forum Kick-off Workshop", at Chemicals Agency (ECHA), Helsinki, Finland on 7-8 December 2023. aim of was gain insight into regulatory use NAMs, with a particular reference Next Generation Risk Assessment (NGRA), chemical safety assessment. To achieve this, presentations summarised learnings and experiences previous EPAA Skin Sensitisation Forums as well that...
Since initial regulatory action in 2010 Canada, bisphenol A (BPA) has been progressively replaced by structurally related alternative chemicals. Unfortunately, many of these chemicals are data-poor, limiting toxicological risk assessment. We used high-throughput transcriptomics to evaluate potential hazards and compare potencies BPA 15 cultured breast cancer cells. MCF-7 cells were exposed (0.0005-100 µM) for 48 h. TempO-Seq (BioSpyder Inc) was examine global transcriptomic changes estrogen...
In 2012, the Council of Canadian Academies published expert panel on integrated testing pesticide’s report titled: Integrating emerging technologies into chemical safety assessment. This was prepared for Government Canada in response to a request from Minister Health and behalf Pest Management Regulatory Agency. It examined scientific status use strategies regulatory health risk assessment pesticides while noting data-rich/poor dichotomy that exists when comparing pesticide formulations most...
Abstract Concerns about the potential adverse effects of bisphenol A (BPA) have led to an increase in use replacements, yet toxicity data for several these chemicals are limited. Using high-content imaging, we compared BPA, BPAF, BPF, BPS, BPM, and BPTMC germ (C18-4 spermatogonial) steroidogenic (MA-10 Leydig KGN granulosa) cell lines. Effects on viability phenotypic markers were analyzed determine benchmark concentrations (BMCs) estimate administered equivalent doses (AEDs). In all 3 lines,...
Read-across is an in silico method applied chemical risk assessment for data-poor chemicals. The read-across outcomes repeated-dose toxicity end points include the no-observed-adverse-effect level (NOAEL) and estimated uncertainty a particular category of effects. We have previously developed new paradigm estimating NOAELs based on chemoinformatics analysis experimental study qualities from selected analogues, not relying quantitative structure–activity relationships (QSARs) or rule-based...
Bisphenol A (BPA), a widely used chemical in the production of plastics and epoxy resins, has garnered significant attention due to its association with adverse health effects, particularly endocrine-disrupting properties. Regulatory measures aimed at reducing human exposure BPA have led proliferation alternative chemicals various consumer industrial products. While these alternatives serve reduce exposure, concerns arisen regarding their safety potential toxicity as regrettable substitutes....
Existing Quantitative Structure–Activity Relationship (QSAR) models have limited predictive capabilities for aromatic azo compounds. In this study, 2 new were built to predict Ames mutagenicity of class The first one made use descriptors based on simplified molecular input-line entry system (SMILES), calculated with the CORAL software. second model was k-nearest neighbors algorithm. statistical quality predictions from single satisfactory. performance further improved when these combined....
Current global efforts are aiming to increase use of mechanistic information in regulatory testing. In tiered testing paradigms, vitro, silico, and vivo studies employed progressively identify classify health hazards, which then compared against human equivalent doses. We used data from three companion papers on the brominated flame retardant hexabromocyclododecane (HBCD) conduct a case study included ToxCast™ vitro-in extrapolation (Tier 1), rat liver transcriptomic 2), conventional 3)...
Internationally, there are thousands of existing and newly introduced chemicals in commerce, highlighting the ongoing importance innovative approaches to identify emerging concern. For many chemicals, is a paucity hazard exposure data. Thus, crucial need for efficient robust address data gaps support risk-based prioritization. Several studies have demonstrated utility vitro bioactivity from ToxCast program deriving points departure (PODs). contains nearly 1,400 endpoints per chemical,...