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Study Explores Impact of Early Bisphenol A Exposure on Rat Enamel

June 27, 2013

The July 2013 issue of the American Journal of Pathology includes a study that found hypomineralized enamel in month-old rats that were exposed daily, in utero and after birth, to bisphenol A (BPA).1 The study aimed to mimic human exposure to BPA by evaluating the possible effects on enamel development in laboratory rats, which were treated with BPA during the fetal and suckling periods when teeth develop. After 30 days, the BPA-treated rats exhibited enamel defects and changes in elemental composition of incisors. The effects were reportedly similar to those observed in human teeth diagnosed with molar incisor hypomineralization (MIH), a developmental defect that originates in the enamel maturation phase. The researchers suggested that chronic BPA exposure early in life may influence the development of MIH, and the study received online news coverage from The Dental Tribune2 and other news agencies.

In the study, researchers orally administered 5 μg/kg of BPA in corn oil daily to a group of pregnant rats, and dosing for the treated rat offspring continued from conception until sacrifice (after 30 or 100 days). A control group of rats received identical treatment, but was fed with only BPA-free corn oil. After sacrifice, enamel defects on the rats’ mandibular incisors were examined and scored. After 30 days, 75 percent of BPA-treated rat incisors showed enamel defects, whereas all incisors of rats in the control group were unaffected. Immunohistochemistry revealed that the enamelin (an enamel protein) and serum albumin content of BPA-treated incisors increased during the maturation stage compared to controls.

To evaluate the effects of BPA exposure on rat amelogenesis further, rat HAT-7ameloblastic cells were cultured and treated with BPA for 48 hours. The researchers identified an increased expression of enamelin, but decreased expression of kallikrein 4 (a proteinase associated with enamel mineralization).3 At 100 days of age, the BPA-treated rats had incisors that were indistinguishable from the control rats with regard to mRNA expression, phenotype, or organic content of enamel. Given this, the authors posit that rat amelogenesis (the developmental process of enamel formation) may only be susceptible to BPA in an early developmental stage, but any period of susceptibility to MIH does not continue indefinitely.

The research team also extracted 10 teeth from human patients diagnosed with MIH and ten control teeth and scored them using the same criteria as for the rat incisors. The MIH-diagnosed human teeth exhibited phenotypically similar enamel defects and a similarly abnormal accumulation of organic material as the BPA-treated rat teeth. MIH preferentially affects permanent incisors and first molars, which begin to mineralize between birth and five months of age. The study authors hypothesize that this is the period in which exposure to BPA may affect enamel maturation in humans, thus leading to the development of MIH.

MIH is a common clinical condition affecting approximately 18 percent of children between six and eight years of age, but its etiology remains unclear. The severity of the condition varies widely, but MIH molars are typically fragile, hypersensitive, and develop caries easily.4 The prevalence of MIH also appears to be increasing, and as attention to this disorder grows, so do calls for further research to clarify its etiology.5 Previously investigated potential risk factors in development of hypomineralized enamel include premature birth, childhood infections, and antibiotic use.6,7

The new study suggests possible molecular mechanisms by which BPA may affect enamel formation in rats. However, the method by which BPA may affect gene expression in rat ameloblasts remains unknown and requires further research. Additionally, whether BPA has the same mechanisms of action in human teeth as in rats remains unknown. The observed effect of BPA may be exaggerated in rat teeth compared to human teeth because humans metabolize BPA more quickly than rodents, and rat incisors grow continuously, unlike human teeth. No human epidemiological research has yet examined any association between MIH and BPA.

Any exposure from resin-based materials would also be short-lived and at a dose many times lower than the rats’ daily dose. Food and beverages account for the majority of human exposure to BPA, and dental sealants are considered to have little relevance in estimating exposure to BPA. Further, resinbased dental materials are generally not placed in human infants during the proposed period of susceptibility to BPA, so any risk of MIH associated with long-term exposure to restorative materials is unlikely.

The following resources on BPA are also available for more information:

1Jedeon K., De la Dure-Molla M., Brookes S, Loiodice S, Marciano C, Kirkham J, Canivenc-Lavier M., Boudalia S., Bergès R., Harada H., Berdal A, Babajko S. Enamel defects reflect perinatal exposure to bisphenol A. Am J Path 2013 Jul; 183(1):
2Early BPA exposure may adversely affect formation of tooth enamel. Dental Tribune. June 13, 2013. Accessed June 13, 2013.
3Smith C., Richardson A., Hu Y, Bartlett J., Hu J., Simmer J. Effect of kallikrein 4 on loss of enamel mineralization: comparison with mice lacking matrix metalloproteinase 20. J Biol Chem. 2011 May;
4Weerheijm K. Molar incisor hypomineralisation (MIH). Eur J Paediatr Dent. 2003 Sep; 4(3):114-20.
5Garg N., Jain A., Saha S., Singh J. Essentiality of early diagnosis of molar incisor hypomineralization in children and review of its clinical presentation, etiology and management. Int J Clin Pediatr Dent. 2012; 5(3):190-6.
6Alaluusua S. Aetiology of molar-incisor hypomineralisation: a systematic review. Eur Arch Paediatr Dent 2010; 11(2), 53-58.
7Crombie F, Manton D, Kilpatrick N. Aetiology of molar-incisor hypomineralization: a critical review. Int J Paediatr Dent 2009;19(2), 73-83.

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