Romanian Society of Pharmaceutical Sciences
 

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DEVELOPMENTAL EXPOSURE TO REGULATORY PERMITTED DOSES OF GLYPHOSATE AND A GLYPHOSATE, DICAMBA, 2,4-D MIXTURE INDUCES HISTOPATHOLOGICAL ALTERATIONS IN TESTES AND PROSTATE OF MALE RATS

MOHAMAD ALAA HBOUS 1, LILIANA CERCELARU 2*, RADU MITRUT 3, ANTONIA BLENDEA 4, ROBIN MESNAGE 5,6, MICHAEL N ANTONIOU 5, ANCA OANA DOCEA 7

1 Doctoral School, University of Medicine and Pharmacy of Craiova, Romania
2 Department of Anatomy and Embryology, University of Medicine and Pharmacy of Craiova, Romania
3 Department of Cardiology, County Emergency Clinical Hospital of Craiova, Craiova, Romania
4 Department of Pharmaceutical Botany, University of Medicine and Pharmacy of Craiova, 200349, Craiova, Romania
5 King'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, United Kingdom
6 Buchinger Wilhelmi Clinic, Wilhelmi-Beck-Straße 27, 88662 Überlingen, Germany
7 Department of Toxicology, University of Medicine and Pharmacy of Craiova, Romania

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Glyphosate is the most widely used herbicide worldwide and is frequently applied in combination with dicamba and 2,4- dichlorophenoxyacetic acid (2,4-D) in agricultural settings. Although regulatory reference values have been established for these compounds, concerns persist regarding their potential reproductive effects, particularly following prolonged exposure during sensitive developmental periods. This study evaluated whether chronic developmental exposure to glyphosate at Eu- ropean Union (EU) regulatory reference doses, namely the acceptable daily intake (ADI) and the no-observed-adverse-effect level (NOAEL), as well as to a mixture of glyphosate, dicamba, and 2,4-D at their respective EU ADI levels, induces hormo- nal and histopathological alterations in male reproductive organs. Pregnant Wistar rats were exposed from gestational day 6 through lactation, and male offspring continued treatment after weaning until postnatal day 111. At the end of the exposure period, serum testosterone levels, relative testis weight, and histopathological changes in testes and prostate were assessed. The herbicide mixture significantly decreased serum testosterone and increased relative testis weight. Histological analysis revealed progressive testicular and prostatic lesions, suggesting that developmental exposure to this herbicide mixture may disrupt male reproductive structure and endocrine homeostasis.