矢上 晶子

Cosmetic and quasi-drug ingredients intended for daily use require reliable skin irritation assessment. However, restrictions on animal testing, including the European Union marketing ban for cosmetics tested on animals, have prompted the adoption of reconstructed human epidermis (RhE) assays, such as Organization for Economic Co-operation and Development (OECD) Test Guideline 439 (TG439). Although TG439 identifies Globally Harmonized System of Classification and Labelling of Chemicals (GHS) Category 2 irritants and No Category (non-irritant) chemicals as an alternative to the 4-h rabbit skin irritation test, its ability to predict human responses to 24-h exposure and mild irritation remains limited. This study evaluated the reproducibility of TG439 across six laboratories using LabCyte EPI-MODEL24 and a standardized stepwise dilution design. TG439 was used to determine a "TG439 non-irritant concentration" for 17 test substances. Human 24-h closed patch tests were then performed using stepwise escalation to one-quarter and one-half of this concentration, with predefined stopping criteria to ensure subject safety. Inter-laboratory control results confirmed TG439 reproducibility. Most test substances exhibited Sugai's Irritation Index (S.I.I.) values within the "Safe" or "Acceptable" categories at both test concentrations. However, selected surfactants, cationic preservatives, and hair dye intermediates produced elevated S.I.I. values, requiring discontinuation of concentration escalation and highlighting the importance of predefined stopping criteria. These findings support TG439 as a practical starting point for human irritation testing when combined with a stepwise concentration approach and predefined safety criteria, enabling the ethical translation of in vitro findings to human testing and extending TG439-based evaluation beyond "harmless ingredients."

PURPOSE: To report our experience with two cases of acrylate allergy confirmed by patch testing, wherein acrylic intraocular lens (IOL) implantation was performed and followed up for 1 year. OBSERVATIONS: A 78-year-old woman with an allergy to acrylic resin consulted a general allergist because of suspected depigmented contact dermatitis. A patch test was positive for methyl methacrylate and 2-hydroxyethyl methacrylate (2-HEMA), which are acrylic resins. Before cataract surgery, patch tests for the IOL and other acrylic resin materials were performed, all of which tested negative. Case 2: A 49-year-old woman was allergic to several substances, including acrylic resin. A patch test was positive for 2-HEMA and ethylene glycol dimethacrylate. We consulted an anesthesiologist regarding immediate-type allergy and explained to the patient about the possibility of IOL removal for delayed-type allergy. Intra-or postoperative complications were not observed in either patient. Postoperative inflammation was similar to that observed after conventional cataract surgeries. During the 1-year follow-up period, worsening of inflammation in the anterior chamber or other symptoms indicative of delayed hypersensitivity were not observed. CONCLUSIONS AND IMPORTANCE: In two patients with cutaneous acrylate allergy, hydrophobic acrylic IOL implantation was uneventful through the 1-year follow-up period. Careful preoperative patch testing, allergist collaboration, informed consent about uncertain long-term risk, and close follow-up are advised.

PURPOSE: Increasing attention has been paid to individuals who report gastrointestinal symptoms following wheat consumption. In addition to wheat allergy and celiac disease, non-celiac gluten sensitivity (NCGS) has been proposed as a clinical entity. Despite persistent symptoms, many affected individuals continue to consume wheat-containing foods. We aimed to investigate the impact of replacing wheat-based foods with gluten-reduced foods, specifically yellow pea pasta (YPP), bread (YPB), and chips (YPC), on the abdominal symptoms, quality of life (QOL), and gut microbiota in healthy individuals who habitually consume wheat frequently. METHODS: Thirty men and women aged 18-64 years with habitual high wheat intake were enrolled and divided into two groups based on the presence or absence of abdominal symptoms. Participants followed a 4-week gluten-reduced diet intervention using YPP, YPB, and YPC. Abdominal symptoms, QOL, gut microbiota, and selected blood biomarkers were evaluated before and after the intervention. RESULTS: The intervention led to significant improvement in abdominal distension, abdominal pain or discomfort, feeling of incomplete evacuation, hard stools, and urgent need for defecation. Baseline QOL differences between groups were no longer evident. Analysis of gut microbiota revealed maintenance and/or an increase in short-chain fatty acid-producing bacteria, with significant correlations observed between specific bacterial shifts and symptom improvement. CONCLUSIONS: Yellow pea-based products (YPP, YPB, and YPC) may represent a promising dietary strategy for alleviating abdominal symptoms in individuals with high wheat consumption. This study was registered in the UMIN Clinical Trials Registry (UMIN Trial ID: UMIN000056466).