Christine Austin1, Cardius Richardson2, Donald Smith3, Manish Arora4. 1. Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Institute of Dental Research, Westmead Millennium Institute, Westmead Hospital, and Oral Pathology and Oral Medicine, Faculty of Dentistry, University of Sydney, Sydney, NSW, Australia. 2. Microbiology and Environmental Toxicology, University of California, Santa Cruz, CA, USA. 3. Microbiology and Environmental Toxicology, University of California, Santa Cruz, CA, USA. Electronic address: drsmith@ucsc.edu. 4. Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: manish.arora@mssm.edu.
Abstract
BACKGROUND: Neonates and children are particularly vulnerable to the toxic effects of excess manganese (Mn), but studies of Mn exposure during these developmental periods are hampered by a lack of validated biomarkers. Deciduous teeth may be used to assess Mn exposure during these developmental periods but require further validation to determine the relationship between tooth Mn, Mn in target tissues, and exposure. OBJECTIVES: To determine the relationship of tooth Mn concentrations with: (i) exposure dose, (ii) the timing/duration of exposure, and (iii) with Mn concentrations in blood, brain and bone. METHODS: Rats in different treatment groups were orally exposed to 0, 25 or 50µg/g/day Mn either from postnatal day (PND) 1 - 21 and culled at PND 24, from PND 1 - 21 and culled as adults (>PND 290), or from PND 1 - throughout life and culled at >290 PND. Mn was measured in second molars, femurs, brain and blood by ICP-MS. RESULTS: Tooth Mn increased significantly with dose in rats exposed for 21 PND and culled at 24 PND (p<0.001). In rats culled at >290 PND, tooth Mn increased with exposure duration (p<0.001) and reflected exposure duration. A significant, positive association between tooth Mn and Mn levels in blood (Spearman's rho 0.69, p<0.01) brain (rho 0.59, p<0.05) and bone (rho 0.69, p<0.01) was observed in animals with lifelong exposure. Tooth Mn and Mn levels in bone were also significantly positively associated in animals exposed only early in life (rho 0.76, p<0.001). CONCLUSIONS: Teeth are a sensitive biomarker of active and past Mn exposure and Mn burden in tissues. Unlike blood, teeth retain information on exposure history over the short and long-term.
BACKGROUND: Neonates and children are particularly vulnerable to the toxic effects of excess manganese (Mn), but studies of Mn exposure during these developmental periods are hampered by a lack of validated biomarkers. Deciduous teeth may be used to assess Mn exposure during these developmental periods but require further validation to determine the relationship between tooth Mn, Mn in target tissues, and exposure. OBJECTIVES: To determine the relationship of tooth Mn concentrations with: (i) exposure dose, (ii) the timing/duration of exposure, and (iii) with Mn concentrations in blood, brain and bone. METHODS:Rats in different treatment groups were orally exposed to 0, 25 or 50µg/g/day Mn either from postnatal day (PND) 1 - 21 and culled at PND 24, from PND 1 - 21 and culled as adults (>PND 290), or from PND 1 - throughout life and culled at >290 PND. Mn was measured in second molars, femurs, brain and blood by ICP-MS. RESULTS: Tooth Mn increased significantly with dose in rats exposed for 21 PND and culled at 24 PND (p<0.001). In rats culled at >290 PND, tooth Mn increased with exposure duration (p<0.001) and reflected exposure duration. A significant, positive association between tooth Mn and Mn levels in blood (Spearman's rho 0.69, p<0.01) brain (rho 0.59, p<0.05) and bone (rho 0.69, p<0.01) was observed in animals with lifelong exposure. Tooth Mn and Mn levels in bone were also significantly positively associated in animals exposed only early in life (rho 0.76, p<0.001). CONCLUSIONS: Teeth are a sensitive biomarker of active and past Mn exposure and Mn burden in tissues. Unlike blood, teeth retain information on exposure history over the short and long-term.
Authors: David J Bellis; Katherine M Hetter; Joseph Jones; Dula Amarasiriwardena; Patrick J Parsons Journal: Environ Res Date: 2007-07-20 Impact factor: 6.498
Authors: Jeffry D Schroeter; Andy Nong; Miyoung Yoon; Michael D Taylor; David C Dorman; Melvin E Andersen; Harvey J Clewell Journal: Toxicol Sci Date: 2010-12-27 Impact factor: 4.849
Authors: C Santos-Burgoa; C Rios; L A Mercado; R Arechiga-Serrano; F Cano-Valle; R A Eden-Wynter; J L Texcalac-Sangrador; J P Villa-Barragan; Y Rodriguez-Agudelo; S Montes Journal: Environ Res Date: 2001-02 Impact factor: 6.498
Authors: Manish Arora; Asa Bradman; Christine Austin; Michelle Vedar; Nina Holland; Brenda Eskenazi; Donald R Smith Journal: Environ Sci Technol Date: 2012-04-11 Impact factor: 9.028
Authors: Ami R Zota; Adrienne S Ettinger; Maryse Bouchard; Chitra J Amarasiriwardena; Joel Schwartz; Howard Hu; Robert O Wright Journal: Epidemiology Date: 2009-05 Impact factor: 4.822
Authors: Robert B Gunier; Ana Maria Mora; Donald Smith; Manish Arora; Christine Austin; Brenda Eskenazi; Asa Bradman Journal: Environ Sci Technol Date: 2014-11-21 Impact factor: 9.028
Authors: Donna J Coetzee; Patricia M McGovern; Raghavendra Rao; Lisa J Harnack; Michael K Georgieff; Irina Stepanov Journal: Environ Health Date: 2016-08-30 Impact factor: 5.984
Authors: Andrea E Cassidy-Bushrow; Alexandra R Sitarik; Suzanne Havstad; Sung Kyun Park; Lawrence F Bielak; Christine Austin; Christine Cole Johnson; Manish Arora Journal: Environ Int Date: 2017-09-05 Impact factor: 9.621
Authors: Julia Anglen Bauer; Roberta F White; Brent A Coull; Christine Austin; Manuela Oppini; Silvia Zoni; Chiara Fedrighi; Giuseppa Cagna; Donatella Placidi; Stefano Guazzetti; Qiong Yang; David C Bellinger; Thomas F Webster; Robert O Wright; Donald Smith; Megan Horton; Roberto G Lucchini; Manish Arora; Birgit Claus Henn Journal: Neurotoxicology Date: 2021-08-31 Impact factor: 4.294
Authors: Erik de Water; Demetrios M Papazaharias; Claudia Ambrosi; Lorella Mascaro; Emilia Iannilli; Roberto Gasparotti; Roberto G Lucchini; Christine Austin; Manish Arora; Cheuk Y Tang; Donald R Smith; Robert O Wright; Megan K Horton Journal: PLoS One Date: 2019-08-14 Impact factor: 3.752
Authors: Megan K Horton; Leon Hsu; Birgit Claus Henn; Amy Margolis; Christine Austin; Katherine Svensson; Lourdes Schnaas; Chris Gennings; Howard Hu; Robert Wright; Martha María Téllez Rojo; Manish Arora Journal: Environ Int Date: 2018-09-08 Impact factor: 13.352
Authors: Birgit Claus Henn; Christine Austin; Brent A Coull; Lourdes Schnaas; Chris Gennings; Megan K Horton; Mauricio Hernández-Ávila; Howard Hu; Martha Maria Téllez-Rojo; Robert O Wright; Manish Arora Journal: Environ Res Date: 2018-02 Impact factor: 8.431
Authors: Paul Curtin; Christine Austin; Austen Curtin; Chris Gennings; Claudia Figueroa-Romero; Kristen A Mikhail; Tatiana M Botero; Stephen A Goutman; Eva L Feldman; Manish Arora Journal: PLoS Comput Biol Date: 2020-04-15 Impact factor: 4.475