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Flavouring Group Evaluation 87, Revision 3 (FGE.87Rev3): Consideration of bicyclic secondary alcohols, ketones and related esters evaluated by JECFA (63rd meeting) structurally related to bicyclic secondary alcohols, ketones and related esters evaluated in FGE.47Rev1
Publication . EFSA Panel on Food Additives and Flavourings (FAF); Castle, Laurence; Andreassen, Monica; Aquilina, Gabriele; Bastos, Maria; Boon, Polly; Fallico, Biagio; FitzGerald, Rex; Frutos Fernández, María José; Grasl‐Kraupp, Bettina; Gundert‐Remy, Ursula; Gürtler, Rainer; Houdeau, Eric; Kurek, Marcin; Louro, Henriqueta; Morales, Patricia; Passamonti, Sabina; Benigni, Romualdo; Degen, Gisela; Engel, Karl‐Heinz; Carfí, Maria; Martino, Carla
The Panel on Food Additives and Flavourings (FAF) of the European Food Safety Authority was requested to consider evaluations of flavouring substances assessed since 2000 by the Joint FAO/WHO Expert Committee on Food Additives (the JECFA) and to decide whether further evaluation is necessary, as laid down in Commission Regulation (EC) No. 1565/2000. The present consideration concerns a group of 19 bicyclic secondary alcohols, ketones and related esters evaluated by JECFA at the 63rd meeting. This revision of FGE.87 is made due to new information on annual production volume, allowing the calculation of maximised survey‐derived daily intake (MSDI) for 4,4a,5,6‐tetrahydro‐7‐methylnaphthalen‐2(3H)‐one [FL‐no: 07.136]. In addition, new data on uses and use levels for the substances [FL‐no: 07.089, 07.0136, 07.153 and 07.159] have been provided and considered for the estimation of exposure (mTAMDI approach). For [FL‐no: 07.136], the Panel agrees with the Procedure as applied by JECFA and with JECFA conclusion: ‘No safety concern at estimated levels of intake as flavouring substance’, when based on the MSDI approach. For the other 18 substances considered in FGE.87Rev3, the same conclusion was already drawn in FGE.87Rev2. For [FL‐no: 07.136], the mTAMDI exposure estimate is below the TTC for structural class II substances. Accordingly, no further data are required in the context of the current evaluation programme. For [FL‐no: 07.089, 07.153, 07.159], mTAMDI exposure estimates are above the TTC for structural class II substances; therefore, more reliable data on uses and use levels should be provided in order to refine the exposure assessment and to finalise their safety evaluation. For the remaining 15 substances, use levels are needed to calculate the mTAMDIs in order to identify those flavouring substances that need more refined exposure assessments and to finalise the evaluation. Information on specifications for the materials of commerce is considered adequate for all 19 substances.
Safety evaluation of the modification of the food additive enzymatically produced steviol glycosides (E 960c)
Publication . EFSA Panel on Food Additives and Flavourings (FAF); Castle, Laurence; Andreassen, Monica; Aquilina, Gabriele; Bastos, Maria Lourdes; Boon, Polly; Fallico, Biagio; FitzGerald, Rex; Frutos Fernandez, Maria Jose; Grasl-Kraupp, Bettina; Gundert-Remy, Ursula; Gürtler, Rainer; Houdeau, Eric; Kurek, Marcin; Louro, Henriqueta; Morales, Patricia; Passamonti, Sabina; Barat Baviera, José Manuel; Degen, Gisela; Gott, David; Herman, Lieve; Leblanc, Jean-Charles; Moldeus, Peter; Waalkens-Berendsen, Ine; Wölfle, Detlef; Civitella, Consuelo; Dino, Borana; Lunardi, Simone; Mech, Agnieszka; Multari, Samuele; Ruggeri, Laura
The EFSA Panel on Food Additives and Flavourings (FAF Panel) provides a scientific opinion on the safety of a modified manufacturing process for the food additive enzymatically produced steviol glycosides (E 960c). The new process converts purified steviol glycosides extracted from Stevia rebaudiana leaves through enzymatic bioconversion catalysed by glucosyltransferase and sucrose synthase enzymes, both produced using three newly developed genetically modified strains of Escherichia coli (CDX‐044 W3110‐TKO, CDX‐045 W3110‐TKO and CDX‐047 W3110‐TKO). This modification of the manufacturing process yields two distinct preparations of steviol glycosides: SBP1, composed predominantly of rebaudioside M, and SBP2, composed predominantly of rebaudioside D. The modification leads to changes in the definition of the food additive, residual protein, residual solvents, microbiological criteria and particle size. The Panel concurred with the applicant's proposal to introduce two new entries in Commission Regulation (EU) No. 231/2012 corresponding to SBP1, predominantly rebaudioside M, and SBP2, predominantly rebaudioside D. The manufacturing process does not raise a safety concern since no viable cells nor DNA of the production strains remained in the final product; in addition, the food enzyme–total organic solid (TOS) are removed to at least 99%, and consequently, the exposure to the food enzyme–TOS via consumption of SPB1 and SPB2 can be considered negligible. The Panel considered that rebaudioside M and D produced by this new manufacturing process have the same physicochemical characteristics as the corresponding rebaudioside M and D present in E 960c(i), (ii) and (iii); therefore, the biological and toxicological data considered in previous evaluations will also apply to the safety assessment of SBP1 and SBP2. The Panel concluded that there is no safety concern with respect to the proposed modification of the food additive enzymatically produced steviol glycoside E 960c related to the use of the new genetically modified strains of E. coli in the production process of SBP1 and SBP2.
Variation in reporting of heatstroke mortality: evidence from a multi-country study
Publication . Tobias, Aurelio; Honda, Yasushi; Madaniyazi, Lina; Alhamad, Barrak; Lavigne, Erik; Roye, Dominic; Tong, Shilu; de Sousa Zanotti Stagliorio Coelho, Micheline; Huber, Veronica; Urban, Ales; das Neves Pereira da Silva, Susana; Achilleos, Souzana; Parks, Robbie M.; Iñiguez, Carmen; Masselot, Pierre; Vicedo-Cabrera, Ana M.; Armstrong, Ben; Gasparrini, Antonio; Hashizume, Masahiro; Multi-City Multi-Country Collaborative Research Network
Background: Heatstroke represents the most severe manifestation of heat exposure. Heatstroke is rare and under-reported, resulting in limited empirical data on its global incidence and burden. This study aimed to examine geographical variations and temporal trends in reported heatstroke mortality across multiple countries.
Methods: We collected annual heatstroke mortality data from 34 countries participating in the Multi-Country Multi-City Collaborative Research Network between 2000 and 2022, using the ICD-10 code X30. Country-specific mortality rates were estimated using Poisson regression, alongside analyses of annual trends and associations with mean warm-season temperature. We also assessed the proportion of heatstroke deaths relative to both overall heat and extreme heat-attributable all-cause mortality.
Findings: Heatstroke mortality rates varied widely across countries, with Japan reporting the highest rate (5·81 per 1 million population; 95% CI 4·43-7·62), followed by Cyprus (2·51; 1·36-4·61), and China (2·42; 1·21-4·85). By contrast, most countries in Europe, South America, and southeast Asia reported rates of less than one death per 1 million population. Heatstroke mortality increased over time in several countries and was associated with warm-season temperatures in most regions. The proportion of heatstroke deaths relative to overall heat-attributable mortality ranged from less than 1% in many countries to as close to 24% in Japan. When analyses were restricted to deaths attributable to extreme heat, the proportion of heatstroke deaths increased substantially.
Interpretation: Our broad international assessment of heatstroke mortality highlights its distinct patterns compared with overall heat-attributable mortality. The observed variability likely reflects differences in recognition, reporting, and diagnostic practices, while climate exposure and health system capacity influence whether heat-related deaths are identified and recorded as heatstroke.
COVID-19 Vaccine Effectiveness among older adults
Publication . Laniece Delaunay, Charlotte; Mateo-Urdiales, Alberto; Pérez-Gimeno, Gloria; O'Reilly, Karen; Uras, Marina; Erdwiens, Annika; Mlinaric, Ivan; Túri, Gergo; Martínez-Baz, Iván; Meijer, Adam; Rodrigues, Ana Paula; Lazar, Mihaela; Latorre-Margalef, Neus; Lucaccioni, Héloïse; Verdasca, Nuno; Bella, Antonino; Rafael de la Cruz Lopez, Maria Angeles; Kelly, Eva; Enouf, Vincent; Tolksdorf, Kristin; Puzelli, Simona; Ibáñez Pérez, Ana Carmen; Fitzgerald, Margaret; Masse, Shirley; Oh, Djin-Ye; Kaczmarek, Marlena; Bacci, Sabrina; Kissling, Esther; VEBIS Primary Care Vaccine Effectiveness Group
Introduction: From September to November 2025, many European countries launched COVID-19 vaccination campaigns, when SARS-CoV-2 incidence was decreasing after a period of high circulation.1 These campaigns targeted specific groups, including older adults (ie, individuals aged at or above a minimum threshold that varied from age 60 to 70 years across countries). We estimated the effectiveness of COVID-19 vaccines administered during these seasonal vaccination campaigns in Europe against medically attended, symptomatic SARS-CoV-2 infection among older adults, from September 29, 2025, to January 10, 2026.
Global Survey Of Genetic Testing Methods For Familial Hypercholesterolaemia: A Study And Recommendations From The European Atherosclerosis Society Familial Hypercholesterolaemia Studies Collaboration Registry
Publication . Chora, Joana Rita; Karungi, Irene; Elshorbagy, Amany; Stevens, Christophe A.T.; Vallejo-Vaz, Antonio J.; Dharmayat, Kanika I.; Abifadel, Marianne; Aguilar-Salinas, Carlos A.; Alhabib, Khalid F.; Almahmeed, Wael; Alnouri, Fahad; Alonso, Rodrigo; Al-Rasadi, Khalid; Al-Sarraf, Ahmad; Arca, Marcello; Ashaat, Engy A.; Ashavaid, Tester F.; Averna, Maurizio; Banach, Maciej; Becker, Marianne; Binder, Christoph J.; Brunham, Liam R.; Catapano, Alberico L.; Corral, Pablo; Descamps, Olivier S.; Drogari, Euridiki; Durst, Ronen; Ezhov, Marat; Groselj, Urh; Harada-Shiba, Mariko; Holven, Kirsten B.; Hovingh, G. Kees; Khovidhunkit, Weerapan; Lalic, Katarina; Latkovskis, Gustavs; Laufs, Ulrich; Liberopoulos, Evangelos; Lin, Jie; März, Winfried; Mata, Pedro; Matthias, Anne Thushara; Miserez, André R.; Mitchenko, Olena; Nawawi, Hapizah Mohd; Nordestgaard, Børge G.; Panayiotou, Andrie G.; Paragh, György; Petrulioniene, Zaneta; Postadzhiyan, Arman; Reyes, Ximena; Sadiq, Fouzia; Sahebkar, Amirhossein; Santos, Raul D.; Sawhney, J.P.S.; Schunkert, Heribert; Shah, Swarup A.V.; Shek, Aleksandr B.; Soran, Handrean; Su, Ta-Chen; Subramaniam, Tavintharan; Tilney, Myra; Tomlinson, Brian; Truong, Thanh Huong; Tybjærg-Hansen, Anne; Viigimaa, Margus; Vohnout, Branislav; Watts, Gerald F.; Yamashita, Shizuya; Ray, Kausik K.; Raal, Frederick J.; Humphries, Steve E.; Freiberger, Tomas; Bourbon, Mafalda; EAS FHSC
Background and aims: Familial hypercholesterolemia (FH), primarily caused by pathogenic LDLR, APOB, or PCSK9 variants, results in elevated LDL-C and increased cardiovascular risk. Genetic testing offers the definitive diagnosis, yet global approaches to FH genetic testing remain unstandardized. We investigate current testing practices worldwide and provide relevant recommendations.
Methods: A survey was distributed to national lead-investigators (NLIs) of 68 countries in the FH-Studies Collaboration, assessing referral criteria, assay methodologies, target genes, and pathogenicity interpretation methods.
Results: NLIs from centres in 55/68 countries (81%) responded, spanning Africa (N=2), Americas (N=6), Asia (N=20), Europe (N=26), and Oceania (N=1). DLCN scores were the most common reason for referral to genetic testing (adults:72%; children:57%). Simon Broome and MEDPED criteria were reported only by centres from high-income countries (adults: 7% and 2%; children: 12% and 2%). Methods for testing in index versus non-index cases were significantly different (p <0.001). Next-generation sequencing (NGS) was the predominant assay method for index cases (62%), while Sanger sequencing was favoured for non-index (71%). However, these testing techniques did not differ between centres from high- and non-high-income countries for index cases (p=0.74) and non-index cases (p=0.49). Copy-number variants (CNVs) were assessed by 65% of centres, with most integrating CNV analysis into NGS platforms (86%) and others (14%) using multiplex ligation-dependent probe-amplification (MLPA) or microarrays. Screening encompassed LDLR (100%), APOB (97%), PCSK9 (95%), and other genes. Most centres (96%) incorporated pathogenicity interpretation into their reports, adhering largely to American College of Medical Genetics and Genomics guidelines.
Conclusions: FH genetic testing practices vary widely across countries surveyed, emphasizing the need for global standardization to enhance accuracy and comparability of FH diagnoses worldwide. We suggest that genetic testing should include the three FH-causing genes and ideally the five associated/phenocopy genes.