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LONG-TERM EFFECTS OF PRENATAL AND POSTNATAL EXPOSURE TO REGULATORY RELEVANT LEVELS OF GLYPHOSATE AND ITS MIXTURE WITH DICAMBA AND 2,4-D ON KIDNEY HEALTH

VIORICA DINCA 1, MOHAMAD ALAA HBOUS 1, LILIANA CERCELARU 2, CRISTINA MARGINEAN 3 ROBIN MESNAGE 4,5, ALEXANDER E. NOSYREV 6, ARISTIDIS TSATSAKIS 6, ANTONIA RADU 7, DRAGOS GEORGE POPA 8, RADU MITRUT 9, ANCA OANA DOCEA 10*, MICHAEL N. ANTONIOU 4, DANIELA CALINA 11

1Doctoral School, University of Medicine and Pharmacy of Craiova, 200349, Craiova, Romania
2Department of Anatomy and Embryology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
3Department of Internal Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
4King's College London, Gene Expression and Therapy Group, Department of Medical and Molecular Genetics, Faculty of Life Sciences and Medicine, Guy's Hospital, London, SE1 9RT, UK
5Buchinger Wilhelmi Clinic, Wilhelmi-Beck-Straße 27, 88662 Überlingen, Germany
6Center of Bioanalytical Research and Molecular Design, Sechenov First Moscow State Medical University, 119991 Moscow, Russian Federation
7Department of Pharmaceutical Botany, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
8Department of Plastic Surgery, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
9Department of Cardiology, University and Emergency Hospital, 050098 Bucharest, Romania
10Department of Toxicology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
11Department of Clinical Pharmacy, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania

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This study investigated the long-term effects of prenatal and postnatal exposure to regulatory-relevant levels of glyphosate and its mixture with dicamba and 2,4-D on kidney health in rats. Pregnant Wistar rats were exposed to glyphosate at acceptable daily intake (ADI) and no-observed-adverse-effect level (NOAEL) doses or a mixture of glyphosate, dicamba, and 2,4-D at their respective ADI doses from gestational day 6 through lactation and 13 weeks post-weaning. Results showed dose-dependent glomerular and tubular dysfunction in both male and female offspring, with the herbicide mixture producing effects similar to the glyphosate NOAEL dose. Histopathological changes and alterations in kidney injury biomarkers were observed in all treatment groups. The study highlights potential risks of low-dose, long-term exposure to these herbicides, particularly during critical developmental periods, and suggests a need to revise current chemical assessment methods to account for mixture effects and developmental toxicity.