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Acetaminophen, pesticide, and diethylhexyl phthalate metabolites, anandamide, and fatty acids in deciduous molars: potential biomarkers of perinatal exposure

Journal of Exposure Science & Environmental Epidemiology volume 23, pages 190–196 (2013)Cite this article

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Abstract

The developing fetus is particularly vulnerable to adverse effects from pharmaceutical and exogenous chemical exposure. Deciduous teeth primarily form over specific periods from the second trimester in utero through the months after birth. We hypothesized that organic chemicals or their metabolites circulating in the bloodstream may sorb into forming dental tissues and remain stored in the tooth thereafter. Our aims were to devise analytical and preparation methods for potentially toxic or beneficial organic chemicals or metabolites in deciduous teeth and to estimate their detection frequencies. The analgesic acetaminophen was stored at greater concentration in a child's second molar than a first molar, consistent with intake, suggesting that acetaminophen concentration in molars may be a biomarker of acetaminophen exposure during molar formation. Chemicals detected by liquid chromatography/tandem mass spectrometry in molars of 21 typically developing children include the endocannabinoid anandamide (86% of children), acetaminophen (43%), and specific metabolites mono-2-ethylhexyl phthalate (MEHP, of plasticizer di-2-ethylhexyl phthalate, 29%), 3,5,6-trichloro-2-pyridinol (TCPy, of organophosphate (OP) insecticide chlorpyrifos, 10%), and 2-isopropyl-6-methyl-4-pyrimidinol (IMPy, of OP insecticide diazinon, 10%). None of these chemicals has previously been detected in human teeth. Molars from the two oldest subjects contained the largest concentrations of MEHP, TCPy, and IMPy. Potentially protective fatty acids detected by gas chromatography/mass spectrometry after derivatization include docosahexaenoic (19%), arachidonic (100%), and linoleic (100%). Validation studies are necessary to verify that each detected chemical in molars provides a biomarker of perinatal exposure.

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References

  1. Perera F.P., Rauh V., Whyatt R.M., Tsai W.-Y., Tang D., Diaz D., et al. Effect of prenatal exposure to airborne polycyclic aromatic hydrocarbons on neurodevelopment in the first three years of life among inner-city children. Environ Health Perspect 2006: 114: 1287–1292.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Perera F.P., Li Z., Whyatt R., Hoepner L., Wang S., Camann D., and Rauh V. Prenatal polycyclic aromatic hydrocarbon exposure and child intelligence at age 5. Pediatrics 2009: 124: e195–e202.

    Article  PubMed  Google Scholar 

  3. Rauh V., Aurunajadai S., Horton M., Perera F., Hoepner L., Barr D., et al. Seven-year neurodevelopmental scores and prenatal exposure to chlorpyrifos, a common agricultural pesticide. Environ Health Perspect 2011: 119: 1196–1201.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Bouchard M.F., Chevrier J., Harley K.G., Kogut K., Vedar M., Calderon N., et al. Prenatal exposure to organophosphate pesticides and IQ in 7-year-old children. Environ Health Perspect 2011: 119 (8): 1189–1195.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Engel S.M., Wetmur J., Chen J., Zhu C., Barr D.B., Canfield R.L., and Wolff M.S. Prenatal exposure to organophosphates, paraoxonase 1, and cognitive development in childhood. Environ Health Perspect 2011: 119 (8): 1182–1188.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Horton M.K., Rundle A., Camann D.E., Barr D.B., Rauh V.A., and Whyatt R.M. Impact of prenatal exposure to piperonyl butoxide and permethrin on 36-month neurodevelopment. Pediatrics 2011: 127: e699–e706.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Herbstman J.B., Sjodin A., Kurzon M., Lederman S.A., Jones R.S., Rauh V., et al. Prenatal exposure to PBDEs and neurodevelopment. Environ Health Perspect 2010: 118 (5): 712–719.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Perzanowski M.S., Miller R.L., Tang D., Ali D., Garfinkel R.S., Chew G.L., et al. Prenatal acetaminophen exposure and risk of wheeze at age 5 years in an urban low-income cohort. Thorax 2010: 65: 118–123.

    Article  PubMed  Google Scholar 

  9. Schultz S.T., Klonoff-Cohen H.S., Wingard D.L., Akshoomoff N.A., Macera C.A., and Ming J. Acetaminophen (paracetamol) use, measles-mumps-rubella vaccination, and autistic disorder: the results of a parent survey. Autism 2008: 12 (3): 293–307.

    Article  PubMed  Google Scholar 

  10. Becker K.G., and Schultz S.T. Similarities in features of autism and asthma and a possible link to acetaminophen use. Medical Hypotheses 2010: 74 (1): 7–11.

    Article  CAS  PubMed  Google Scholar 

  11. Schultz S.T. Can autism be triggered by acetaminophen activation of the endocannabinoid system? Acta Neurobiol Exp (Wars) 2010: 70 (2): 227–231.

    Google Scholar 

  12. Gray Jr L.E., Ostby J., Furr J., Price M., Veeramachaneni D.N.R., and Parks L. Perinatal exposure to the phthalates DEHP, BBP, and DINP, but not DEP, DMP, or DOTP, alters sexual differentiation of the male rat. Toxicol Sci 2000: 58: 350–365.

    Article  CAS  PubMed  Google Scholar 

  13. Swan S.H., Liu F., Hines M., Kruse R.L., Wang C., Redmon J.B., et al. Prenatal phthalate exposure and reduced masculine play in boys. Int J Andol 2010: 33 (2): 259–269.

    Article  CAS  Google Scholar 

  14. Schultz S., DeSilva M., Gu T.T., Qiang M., and Whang K. Effects of the analgesic acetaminophen (paracetamol) and its para-aminophenol metabolite on viability of mouse-cultured cortical neurons. Basic Clin Pharmacol Toxicol 2011; 110: 141–144.

    Article  PubMed  Google Scholar 

  15. Lauritzen L., Hansen H.S., Jorgensen M.H., and Michaelsen K.F. The essentiality of long chain n–3 fatty acids in relation to development and function of the brain and retina. Prog Lipid Res 2001: 40: 1–94.

    Article  CAS  PubMed  Google Scholar 

  16. Prout R., Odutuga A., and Tring F. Lipid analysis of rat enamel and dentine. Archs Oral Biol 1973: 18: 373–380.

    Article  CAS  Google Scholar 

  17. CDC. Fourth National Report on Human Exposure to Environmental Chemicals. Depatment of Health and Human Services, Centers for Disease Control and Prevention, Atlanta, GA, 2009, pp. 275–283. Available for download at http://www.cdc.gov/exposurereport/.

  18. Das S.K., and Harris R.S. Fatty acids in the tooth lipids of 16 animal species. J Dent Res 1970: 49: 119–125.

    Article  CAS  PubMed  Google Scholar 

  19. Cattaneo C., Gigli F., Lodi F., and Grandi M. The detection of morphine and codeine in human teeth: an aid in the identification and study of human skeletal remains. J Forensic Odontostomatol 2003: 21 (1): 1–5.

    CAS  PubMed  Google Scholar 

  20. Marchei E., Joya X., Garcia-Algar O., Vall O., Pacifici R., and Pichini S. Ultrasensitive detection of nicotine and cotinine in teeth by high-performance liquid chromatography/tandem mass spectrometry [letter]. Rapid Commun Mass Spectrom 2008: 22: 2609–2612.

    Article  CAS  PubMed  Google Scholar 

  21. Jan J., Milka V., Azra P., Dominik G., and Matjaz Z. Distribution of organochlorine pollutants in ovine dental tissues and bone. Environ Toxicol Pharmacol 2006: 21: 103–107.

    Article  CAS  PubMed  Google Scholar 

  22. Cadas H., di Tomaso E., and Piomelli D. Occurrence and biosynthesis of endogenous cannabinoid precursor, N-arachidonoyl phosphatidylethanolamine, in rat brain. J Neurosci 1997: 17 (4): 1226–1242.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Högestätt E.D., Jönsson B.A.G., Ermund A., Andersson D.A., Björk H., Alexander J.P., et al. Conversion of acetaminophen to the bioactive N-acylphenolamine AM404 via fatty acid amide hydrolase-dependent arachidonic acid conjugation in the nervous system. J Biol Chem 2005: 280 (36): 31405–31412.

    Article  PubMed  Google Scholar 

  24. Bertolini A., Ferrari A., Otanni A., Guerzoni S., Tacchi R., and Leone S. Paracetamol: new vistas of an old drug. CNS Drug Rev 2006: 12 (3–4): 250–275.

    Article  CAS  PubMed  Google Scholar 

  25. Mallet C., Daulhac L., Bonnefont J., Ledent C., Etienne M., Chapuy E., et al. Endocannabinoid and serotonergic systems are needed for acetaminophen-induced analgesia. Pain 2008: 139: 190–200.

    Article  CAS  PubMed  Google Scholar 

  26. Gulson B.L. Tooth analyses of sources and intensity of lead exposure in children. Environ Health Perspect 1996: 104 (3): 306–312.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. García-Godoy F., and Hicks M.J. Maintaining the integrity of the enamel surface: the role of dental biofilm, saliva and preventive agents in enamel demineralization and remineralization. J Am Dent Assoc 2008: 139 (Suppl): 25S–34S.

    Article  PubMed  Google Scholar 

  28. Nelson S.J., and Ash M.M. Wheeler's Dental Anatomy, Physiology and Occlusion. Saunders, St. Louis, MO, 2010.

    Google Scholar 

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Acknowledgements

We thank Hamed Edrisi and Chris Gourley, Southwest Research Institute, for technical support, the reviewers for constructive probing comments, and Manish Arora, Harvard University, for dental intake perspective. This work was funded primarily by Southwest Research Institute as an internal research project, with support from The Institute for Integration of Medicine and Science/Clinical and Translational Science Award (UL1RR025767) and initial support from Naval Medical Research Unit San Antonio.

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Authors and Affiliations

  1. Analytical and Environmental Chemistry Department, Southwest Research Institute, San Antonio, Texas, USA

    David E Camann, Alice Y Yau & Michelle M Zuniga

  2. Department of Family & Community Medicine, University of Texas Health Science Center, San Antonio, Texas, USA

    Stephen T Schultz, Lynne P Heilbrun, Raymond F Palmer & Claudia S Miller

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  1. David E Camann
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Correspondence to David E Camann.

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Camann, D., Schultz, S., Yau, A. et al. Acetaminophen, pesticide, and diethylhexyl phthalate metabolites, anandamide, and fatty acids in deciduous molars: potential biomarkers of perinatal exposure. J Expo Sci Environ Epidemiol 23, 190–196 (2013). https://doi.org/10.1038/jes.2012.71

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