Bioavailability of tattoo inks by quantifying the marker substances 4-aminobenzoic acid, 2-phenoxyethanol and iodide in blood and urine after tattooing 24 male test persons with black or red color - Tat_BioV

开始日期2021-12-01

申办/合作机构

Bundesinstitut Fur Risikobewertung

100 项与 Bundesinstitut Fur Risikobewertung 相关的临床结果

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0 项与 Bundesinstitut Fur Risikobewertung 相关的专利（医药）

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3,217

项与 Bundesinstitut Fur Risikobewertung 相关的文献（医药）

2025-06-01·Toxicology

NAM-based analysis of contaminant short-term organ toxicity in HepaRG and RPTEC/TERT1 cells

Article

作者: Braeuning, Albert ; Marx-Stoelting, Philip ; Sommersdorf, Cornelia ; Poetz, Oliver ; Miccoli, Andrea ; Jochum, Kristina ; Tralau, Tewes

New Approach Methodologies (NAMs), including cell culture and multi-level omics analyses, are promising alternatives to animal testing. To become useable for risk assessment purposes, they have to be applicable for different substance groups. One important group of substances is food contaminants, including synthetic chemicals, such as perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA), and natural compounds, such as mycotoxins and pyrrolizidine alkaloids. We tested five known contaminants affecting the liver and/or the kidney - PFOS, PFOA, Aflatoxin B₁ (AB₁), lasiocarpine (Las), and cadmium chloride - using HepaRG and RPTEC/TERT1 cells at non-cytotoxic concentrations for 36 and 72 h. Our NAM-based testing protocol included marker protein analysis for cellular functions and targeted transcriptomics followed by bioinformatics pathway analysis. The effects observed were compared with established in vivo results. Protein analysis indicated various affected pathways in HepaRG cells, with generally fewer effects in RPTEC/TERT1 cells. The strongest transcriptional impact was noted for Las in HepaRG cells. This study demonstrated the test protocol's applicability across different substances, revealing significant differences between HepaRG and RPTEC/TERT1 cell lines. RPTEC/TERT1 cells, while expressing renal-specific CYP enzymes, were less suitable for detecting effects of substances requiring hepatic metabolic activation, like Las and AB₁. Our data supports the concept of specific pathway toxicity, with pathway analysis enabling the prediction of effects based on mechanism rather than target organ. Employing multiple omics techniques provided comprehensive insights into various compound effects, including steatosis, reactive oxygen species production and DNA damage, highlighting the potential of an extended omics approach for advancing toxicological assessments.

2025-06-01·Toxicology

Using new approach methodologies for the identification of a sensitizing co-formulant in a plant protection product

Article

作者: Bloch, Denise ; Seifert, Stefanie ; Martin, Sabine ; Curato, Caterina ; Sonnenburg, Anna ; Willenbockel, Christian Tobias ; Peiser, Matthias ; Siewert, Katherina ; Fritsch, Nele

According to Regulation (EC) No 1272/2008, plant protection products (PPPs) can be classified for skin sensitisation by either considering the full formulation or the individual components. For a fraction of PPPs, an application of both assessment strategies results in discrepant classification results. We here aimed to resolve this discrepancy for PPP 1, an exemplary product, which was classified as sensitizing by a positive local lymph node assay but scored negative by the component-based method. We collected further data, as suggested by the regulation, based on a combination of new approach methodologies (NAMs) covering several key events (KEs) in the adverse outcome pathway model for skin sensitisation. Precisely, we employed quantitative structure activity relationship (QSAR) analysis (KE 1), the human cell line activation test (h-CLAT) complemented by Interleukin-8 release measurements (KE 3) and a novel short-term T cell test that is based on the induced expression of activation markers (KE 4). We tested the complete product, individual co-formulants (CFs) or single substances. PPP 1 tested positive in all in vitro assays. QSAR analysis revealed two CFs containing sensitizing chemicals. Only CF 1 was tested positive in the h-CLAT at a minimal induction threshold of 1.5 mg/mL, being less potent than PPP 1. In the T cell assay, both PPP 1 and CF 1 were tested positive at around 0.1 mg/mL. In conclusion, our results propose a novel integrated NAM-based strategy that should be explored further for skin sensitisation hazard identification of complex mixtures, such as PPPs.

2025-05-01·Toxicology in Vitro

A group of novel polyfluoroether substances affects lipid metabolism in human hepatocyte HepaRG cells less than classic perfluoroalkyl compounds

Article

作者: Buhrke, Thorsten ; Braeuning, Albert ; Sprenger, Heike ; Sadrabadi, Faezeh ; Alker, Wiebke

Per- and polyfluoroalkyl substances (PFAS) are used for numerous industrial applications including the production of fluorosurfactants. Some prominent PFAS, e.g., perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS), are non-degradable and therefore persist in the environment. They display various toxic properties including dysregulation of hepatic lipid metabolism. At the molecular level, these effects are mainly based on a PFAS-mediated activation of the peroxisome proliferator-activated receptor alpha (PPARα). A group of novel, degradable polyfluoroether compounds has been designed as building blocks for the production of alternative, degradable fluorosurfactants. In the present study, we examined the capacity of four of these novel polyfluoroether compounds to induce PPARα activation, increase intracellular triglyceride accumulation, and produce a cytotoxic response. In contrast to some classic PFAS including PFOA and PFOS, the novel compounds neither activated PPARα in a transactivation assay, nor did they induce expression of selected PPARα-dependent target genes in differentiated HepaRG cells, a model for human hepatocytes. They also did not induce triglyceride accumulation in HepaRG cells. The in vitro data indicate that the polyfluoroether compounds tested in the present study are not PPARα agonists. Since PPARα agonist activity is often associated with toxic responses, it can be assumed that these substances are less toxic than classic PFAS such as PFOA and PFOS, at least with respect to PPARα-dependent toxicity mechanisms.

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100 项与 Bundesinstitut Fur Risikobewertung 相关的转化医学

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