Antibody–drug conjugates (ADCs) represent a rapidly advancing class of biological drugs used for cancer treatment. The integration of monoclonal antibodies, connected via chemical linkers, ensures the targeting potential of small-molecule payloads with cytotoxic potency. The United States Food and Drug Administration (USFDA) has announced its plan to phase out in vivo tests for monoclonal antibodies and other drugs with replacement from New Approach methodologies (NAMs) data. NAMs can include in vitro (cell-line and organoid testing), in silico modeling or other innovative approaches that have the capacity to predict the toxicity of compounds including ADCs. Among these proposed NAMs, physiologically based pharmacokinetic (PBPK) modeling has the capacity to provide a mechanistic framework capable of integrating antibody disposition, linker deconjugation dynamics, and payload small-molecule pharmacokinetics (PK). This review provides details about ADC and the developing ADC PBPK model, covering the tissue architecture, two-pore vascular transport, model hierarchy from minimal to whole-body model, parameterization strategies, regulatory scenario, applications, limitations and their future prospects.
Per- and polyfluoroalkyl substances (PFASs) are a large group of synthetic chemicals widely used since the 1950s due to useful properties such as water resistance and durability. Their stability makes them persistent environmental contaminants, often called “forever chemicals.” Thousands of PFASs exist and many of them have been linked to adverse health effects. The increase in knowledge about PFASs has led to regulations on their production and use, at least to reduce their presence in the main sources of human exposure, like food and drinking water. Other sources and exposure routes have been less explored and deserve more attention for proper risk management. Indeed, many PFASs continue to be used in numerous categories of applications. Among those that have not yet received much attention in terms of consumer awareness are personal care products (PCPs) and cosmetics. Cosmetics and PCPs represent an underexplored but potentially important exposure pathway, especially through dermal contact. Studies show that PFASs are present in various products such as foundations, mascaras, sunscreens, and lotions, sometimes even when not listed as ingredients. Biomonitoring studies also indicate associations between cosmetic use and PFAS levels in human tissues. Research remains limited and inconsistent due to the diversity of PFASs, lack of standardized methods, and scarce toxicological data. This review aims to highlight our level of knowledge on the subject, as well as data gaps, to provide guidance for future studies.
Food additives (FAs) are intended to be used to improve the quality of food. Within the European Union, more than 300 FAs are currently authorized. Due to their intensive use, humans consume several different FAs daily. The amount and consumption of FAs themselves are influenced by their individual consumption patterns and brand loyalty. Although humans ingest mixtures of several FAs, the substances are still assessed on an individual basis. This study investigated potential cumulative health risks from FA mixtures using currently available toxicological, occurrence and food-consumption data. Forty-two relevant FAs and food additive groups were selected, as their estimated intake exceeded 50% of their corresponding acceptable daily intake (ADI) and they are authorized in relevant food categories. Toxicological data were screened for FAs, and their endpoints for liver, kidney, gastrointestinal, developmental toxicity, reproductive toxicity and hematotoxicity were identified. Based on the availability of toxicological and analytical data, a mixture of 18 FAs was considered. A potential health concern was identified for kidney toxicity (mRPI: 1.8–10.8, refined mRPI: 0.3–1.6) and developmental toxicity (mRPI: 13.6–56.1, refined mRPI: 0.9–3.1). The main risk drivers were steviol glycosides (E 960 a–d), contributing to 40% of nephrotoxicity risks and 18% of developmental toxicity risks, and glutamic acid—glutamates (E 620–625), contributing to 40% of developmental toxicity risks. The study demonstrates the applicability of the mRPI as a screening and prioritization tool for FA mixtures and highlights the need for improved occurrence and co-exposure data.
Pre-clinical toxicological evaluation is an essential component of ensuring the safety and compatibility of wearable devices with biological systems. Along with the local endpoints of cytotoxicity and irritation, skin sensitization is a core toxicological endpoint. Testing wearable devices, which are often solid and composed of multiple components, presents new challenges for New Approach Methods. In the current proof-of-concept study, we propose a strategy for conducting risk assessment of the individual components and the leachables from wearable devices. The GARDskin Dose-Response assay (OECD TGP 4.106) was used to predict the skin sensitization potency of three acrylate monomers, two acrylamide monomers, and one reactive dye. The GARDskin Medical Device (ISO 10993-10:2021, Annex C) was used to classify MED-2000 extracts spiked with isobornyl acrylate. All chemicals were classified as skin sensitizers. The quantitative potency predictions correlated well with available data from defined approaches and produced near-identical potency rankings. Available human and animal reference data were too sparse and heterogenous to substantiate agreement in potency. Finally, the GARDskin Medical Device assay correctly classified the spiked extract as skin sensitizing. In conclusion, the GARDskin assay and associated applications are well adapted to address the testing requirements for wearable devices.
The occurrence of azithromycin in aquatic environments highlights the need for effective remediation approaches. In this study, three boric acid−modified coconut husk biochars prepared using nominal H3BO3 precursor concentrations of 0.1%, 2%, and 5% were evaluated for azithromycin adsorption from aqueous solution. The materials exhibited different adsorption performances under the investigated conditions, with 5% B−CB showing the highest Langmuir−predicted maximum adsorption capacity (qmax) of 170.45 mg g−1, followed by 2% B−CB (158.84 mg g−1) and 0.1% B−CB (136.92 mg g−1). The equilibrium data were best statistically represented by the Langmuir model among the isotherm models evaluated. Kinetic analysis showed that the pseudo−second−order (PSO) model provided a better statistical description of the adsorption kinetics, with 5% B−CB showing the highest goodness−of−fit (R2 = 0.99), compared with 0.96 and 0.95 for 0.1% and 2% B−CB, respectively. The positive ΔH° values of 11.08, 6.74, and 6.19 kJ mol−1 for 0.1%, 2%, and 5% B−CB, respectively, indicated an endothermic adsorption process under the investigated conditions. FTIR analysis indicated qualitative changes in surface functionalities consistent with boric acid−modified coconut husk biochar following H3BO3−assisted modification; however, the actual boron content of the final biochars was not quantitatively determined. Furthermore, 5% B−CB retained measurable adsorption capacity over five adsorption–desorption cycles, and its fixed−bed performance was evaluated under the investigated operating conditions. Overall, the results indicate that azithromycin adsorption performance varied with the nominal H3BO3 precursor concentration, with 5% B−CB exhibiting the highest adsorption capacity among the materials investigated under the experimental conditions.
