Long-term exposure of mice to sodium fluoride and to a mixture of endocrine disruptors causes tooth enamel and retina abnormalities associated with changes in hepatic metabolism
Abstract
Exposure to environmental pollutants may contribute to various health disorders, often manifesting after a prolonged period of latency. The identification of early markers is, therefore, of paramount importance. To achieve this objective, realistic models of environmental exposure were set up. Whereas most studies consider one substance or mixture with one target organ, here, in addition to the liver, two easily accessible sensitive organs, the eyes and teeth, were analyzed as good potential candidates to be original markers of environmental exposures. C57BL/6J mice were exposed to either sodium fluoride or a mixture of 15 endocrine-disrupting substances, or both, in their drinking water from the time of conception until 1 or 10 months after birth. The doses of these substances were chosen to be close to the tolerable daily intake. All mice in test groups presented lower weight gain than controls with the most significant differences observed in females 30 days after birth. Alterations in the eye retina were detected as early as 1 month of age and considerably worsened by 10 months. Dental defects were observed in all test groups at the last time point. At that age, metabolic disruptions were identified through molecular metabolomic and RNAseq analyses, while histological analyses showed no significant defects in liver. This study shows that chronic exposure to widespread toxicants resulted in hepatic metabolic disorders. However, the most evident histological and clinical signs were observed in eyes and teeth. These easily accessible stigmata may be used as early markers of low-dose exposure to environmental toxicants.
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BibTeX
@article{picard2026longterm,
title = {{Long-term exposure of mice to sodium fluoride and to a mixture of endocrine disruptors causes tooth enamel and retina abnormalities associated with changes in hepatic metabolism}},
author = {Emilie Picard and Fatima Domenica Elisa de Palma and Sophia Loiodice and Vincent Carbonnier and Seiki Achiedo and Noor Mimoun and Diluxe Mutale and Sophie Doublier and Sylvère Durand and Mélanie Bourgin and Fanny Aprahamian and Pierre Cordier and Louise Gutter and Katia Jedeon and Marie-Christine Naud and Philippe Noirez and Jean-Marc Ricort and Lotfi Slimani and Guido Kroemer and Francine Behar-Cohen and Maria Chiara Maiuri and Sylvie Babajko},
journal = {Environment International},
year = {2026},
month = oct,
doi = {10.1016/j.envint.2025.109861},
url = {https://hal.science/hal-05804885v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Long-term exposure of mice to sodium fluoride and to a mixture of endocrine disruptors causes tooth enamel and retina abnormalities associated with changes in hepatic metabolism
AU - Emilie Picard
AU - Fatima Domenica Elisa de Palma
AU - Sophia Loiodice
AU - Vincent Carbonnier
AU - Seiki Achiedo
AU - Noor Mimoun
AU - Diluxe Mutale
AU - Sophie Doublier
AU - Sylvère Durand
AU - Mélanie Bourgin
AU - Fanny Aprahamian
AU - Pierre Cordier
AU - Louise Gutter
AU - Katia Jedeon
AU - Marie-Christine Naud
AU - Philippe Noirez
AU - Jean-Marc Ricort
AU - Lotfi Slimani
AU - Guido Kroemer
AU - Francine Behar-Cohen
AU - Maria Chiara Maiuri
AU - Sylvie Babajko
PY - 2026
DA - 2026/10/18
JO - Environment International
DO - 10.1016/j.envint.2025.109861
UR - https://hal.science/hal-05804885v1
AB - Exposure to environmental pollutants may contribute to various health disorders, often manifesting after a prolonged period of latency. The identification of early markers is, therefore, of paramount importance. To achieve this objective, realistic models of environmental exposure were set up. Whereas most studies consider one substance or mixture with one target organ, here, in addition to the liver, two easily accessible sensitive organs, the eyes and teeth, were analyzed as good potential candidates to be original markers of environmental exposures. C57BL/6J mice were exposed to either sodium fluoride or a mixture of 15 endocrine-disrupting substances, or both, in their drinking water from the time of conception until 1 or 10 months after birth. The doses of these substances were chosen to be close to the tolerable daily intake. All mice in test groups presented lower weight gain than controls with the most significant differences observed in females 30 days after birth. Alterations in the eye retina were detected as early as 1 month of age and considerably worsened by 10 months. Dental defects were observed in all test groups at the last time point. At that age, metabolic disruptions were identified through molecular metabolomic and RNAseq analyses, while histological analyses showed no significant defects in liver. This study shows that chronic exposure to widespread toxicants resulted in hepatic metabolic disorders. However, the most evident histological and clinical signs were observed in eyes and teeth. These easily accessible stigmata may be used as early markers of low-dose exposure to environmental toxicants.
SN - 0160-4120
ER -