Jose Vicente Tarazona

The expected cutaneous adverse effects (CAE) of oncology therapies can be disabling and even force the patient to discontinue treatment. The incorporation of cosmetics into skin care regimens (SCRs) as true therapeutic adjuvants can prevent, control, and avoid sequelae. However, cosmetics may also lead to adverse reactions in patients. The aim of our study was to assess the impact of the tolerability of cosmetics used in routine skin care on quality of life in this vulnerable population group through a survey. In addition, information was collected to improve the knowledge of the beneficial effects of cosmetics and the composition recommended. Hospital nurses guided the patients to fill in the surveys, which were done once. The main uses are related to daily hygiene care, photoprotection, and dermo-cosmetic treatment to prevent or at least reduce the skin’s adverse effects. More than 30% (36.36%) of patients perceived undesirable effects or discomfort with the use of cosmetics (27.27% in the facial area, 27.27% in the body and hands, and 22.73% in the scalp and hair). Intolerance was described for some soaps and creams used in the facial area. This study provides additional evidence on perceived tolerance supporting updates of clinical practice guidelines, highlights consolidated knowledge and evidence on the use of cosmetics, as well as new recommendations on the use and composition of cosmetics intended for oncological patients. There is a need for more knowledge about cosmetic ingredients and formulations, including ingredients of concern, such as endocrine disruptors.

New Approach Methodologies (NAMs) in Next-Generation Risk Assessment (NGRA), integrating toxicokinetics (TK) with toxicodynamics (TD), provides an accurate evaluation of combined chemical exposures. This study assesses pyrethroids, which pose regulatory challenges due to their widespread use and cumulative exposure risks. A tiered NGRA framework was compared with conventional risk assessment (RA) to evaluate regulatory applicability. In Tier 1, ToxCast data established gene and tissue bioactivity indicators, facilitating hypothesis-driven hazard identification. Tier 2 examined combined risk assessments, rejecting the hypothesis of the same mode of action and highlighting inconsistencies in in vitro data and NOAEL/ADI correlations. Tier 3 applied Margin of Exposure (MoE) analysis and TK modeling to realistic exposure estimations for risk assessment screening based on internal doses, identifying tissue-specific pathways as critical risk drivers. Tier 4 refined bioactivity indicators using TK approaches to improve the NAM-based effect assessment, including an in vitro vs. in vivo comparison, with coherent results based on interstitial concentrations, though intracellular estimations remained uncertain. Tier 5 confirmed that dietary exposure in healthy adults is close to but below levels of concern, with bioactivity MoE values remaining below concern thresholds, and in vivo MoEs within the standard safety factors. Nevertheless, the MoEs are insufficient for addressing the additional non-dietary exposure expected from other pyrethroid uses such as biocides or pharmaceuticals. Results demonstrate that NGRA with TK-NAM-based TD offers a nuanced, regulatory-relevant framework for risk assessment. The proposed approach integrates the information on individual pyrethroids using bioactivity indicators; and the re-assessment of regulatory toxicity studies to select organ-relevant NOAELs allowed an improved in vitro-in vivo comparison, demonstrating the capacity of bioactivity-based MoEs for combined exposure assessments. This tiered approach provides key insights for regulatory decision-making, establishing a robust model for evaluating pyrethroids and similar chemical classes.

Risk assessment for cosmetics in the European Union (EU) are triggered by a ban on animal testing and concerns of endocrine disruption (ED). The risk assessment focuses on healthy populations and, for potential ED, includes specific developmental stages as vulnerable due to specific concerns on endocrine effects. However, the assessment focuses on healthy individuals and does not consider that some pathologies may increase dermal absorption and even vulnerability to endocrine disruptors. Data from the EU risk assessment, human pharmacokinetic studies and ToxCast bioactivity were combined in a hypothesis-driven Next-Generation Risk Assessment to identify possible risk drivers for vulnerable populations including oncological patients and atopic dermatitis. In vitro effects are observed at concentration in the order of measured plasmatic levels under normal use patterns. The induction of hepatic enzymes is the most relevant bioactivity endpoint, in line with animal findings. The information on endocrine potential is inconclusive, and the possibility for skin effects and endocrine mechanism linked to tumor induction require further elucidation. The information on octocrylene (CAS number: 6197-30-4) bioactivity is limited, lacking information on the metabolites and the immunotoxicity potential, particularly relevant for oncological patients.