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Possible Association Between Dental Sealants and Urinary Bisphenol A Levels in Children Warrants Additional Biomonitoring and Safety Research
ETIOLOGY/OTHER
ARTICLE ANALYSIS & EVALUATION ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION Dental sealants and restorations and urinary bisphenol A concentrations in children in the 2003-2004 National Health and Nutrition Examination Survey. McKinney C, Rue T, Sathyanarayana S, Martin M, Seminario AL, DeRouen T. J Am Dent Assoc 2014;145(7):745-750.
REVIEWER Nancy Maserejian, ScD
PURPOSE/QUESTION Is there an association between dental sealants or restorations and urinary bisphenol A levels in schoolaged children in the United States?
SOURCE OF FUNDING None reported
TYPE OF STUDY/DESIGN Cross-sectional study
Possible Association Between Dental Sealants and Urinary Bisphenol A Levels in Children Warrants Additional Biomonitoring and Safety Research SUMMARY Subjects The data came from 1001 children age 6 to 19 years in the United States who participated in the National Health and Nutrition Examination Survey (NHANES) 2003–2004 survey. To be included in the analysis, children had to be part of the random subsample undergoing urinary bisphenol A (BPA) measurement and have data on the number of dental sealants or restorations present at the time of the survey. Children in this analysis were diverse in race/ethnicity (59% white, 19% Mexican-American, 9% black, 5% Hispanic, and 8% other race/ethnicity), sex (56% male, 44% female), and socioeconomic status.
Key Risk/Study Factor The key study factor was the number of occlusal-surface sealants observed at the dental examination. Children were grouped based on number of sealants present: 0, 1–3, 4–6, and 7–16 (the maximum observed). Sealants were present in 33.9% of the children, with 6.4% of all children having seven or more sealants present. The observed number of sealants was counted separately from the observed number of restorations used for caries treatment; 50.0% of the children had at least one restoration present, with 21.3% of all children having seven or more restorations. No data on the type of dental materials used (e.g., composite type, amalgam, or manufacturers) were available.
Main Outcome Measure LEVEL OF EVIDENCE Level 3: Other evidence
STRENGTH OF RECOMMENDATION GRADE Not applicable
J Evid Base Dent Pract 2014;14:200-202 1532-3382/$36.00 Ó 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jebdp.2014.10.009
The main outcome measure was urinary BPA levels (ng/mL), analyzed as part of the NHANES study. The authors categorized urinary BPA into quartiles, based on the distribution of values in the sample of 6- to 19-year-olds in the analysis. When analyzed as a continuous number, the authors used geometric means of log-transformed values of BPA level.
Main Results Compared to children with no sealants, children with 7 to 16 sealants had 25% higher mean urinary BPA levels (95% confidence interval: 14%, 82%; P = 0.23). The geometric means in the highest and lowest categories of sealants were 4.34 and 3.54 ng/mL, respectively. An increase of 10 sealants was associated with an increase in mean urinary BPA concentration of 11% (95% confidence interval: 18%, 52%). These findings were adjusted for the potential confounding variables of age, sex, body mass index, parental education level, race/ethnicity, urinary creatinine levels, and serum cotinine concentrations.
Conclusions Although not statistically significant, the direction of the association between sealants and urinary BPA was in line with the hypothesis, i.e.,
JOURNAL OF EVIDENCE-BASED DENTAL PRACTICE
indicating higher urinary BPA concentrations with greater number of sealants. The authors conclude that the study does not provide strong evidence either to refute or support the notion that composite dental materials lead to BPA exposure, and additional studies are necessary to examine the association over time.
COMMENTARY AND ANALYSIS BPA is used in the manufacture of many polycarbonate plastic products and epoxy resins, including resins such as bisGMA that are used in some dental composite materials.1,2 BPA is a known endocrine disruptor, and adverse biological effects have been observed with low doses in laboratory experiments.3 The adverse effects reach broadly, affecting reproductive health (e.g., reduced ovarian response, miscarriage, premature delivery, reduce male sexual function, reduced sperm quality), immune function, liver function, renal function, and cardiovascular disease parameters.2 Epidemiological studies suggest that chronic low-dose BPA exposure is associated with health problems in children and adults,2 but additional research is needed to test whether these associations are truly causal. In addition, more human biomonitoring studies are needed to increase knowledge on the safety of BPA at various exposure levels and from various exposure sources and to allow fully informed risk assessments.4 Rather than conduct a new biomonitoring study, McKinney and colleagues used available data, collected as part of the NHANES 2003–2004, to examine the association between dental sealants and urinary BPA in children. The directions of the observed associations were in accordance with the hypothesis that dental sealants and restorations are a source of BPA exposure, but the confidence intervals were wide and results were not statistically significant. Therefore it was appropriate that the authors did not make a strong conclusion from the findings and did not suggest changes to clinical practice based on these results. Important limitations of this study include the following: (1) data on type of dental material were not available and (2) the study was a cross-sectional ‘‘snapshot’’ of sealant or restoration status and urinary BPA level. Type of dental material is important because different materials are composed of different resins, some of which have no potential for BPA exposure.5 Furthermore, leaching of dental resins differs across manufacturers.5 For example, if there were truly a measurable association between only a particular sealant subtype and urinary BPA level, this association may be missed in this analysis because the analysis had to combine all dental sealants together. For restorations in particular, this is problematic, given the vast variety of materials used in the United States (e.g., amalgam, glass ionomers, and composites using various materials such as bisGMA, UDMA, ormocer, or silorane). If it were known that Volume 14, Number 4
certain geographic or socioeconomic subgroups are more likely to use traditional composite restorations, it would have been helpful to conduct additional analysis within those subgroups (e.g., stratify analysis by high or low socioeconomic status) to possibly minimize variation in restoration type and confounding by socioeconomic predictors of BPA level. In addition, because the study was cross-sectional, it is unknown if urinary BPA levels increased after the placement of dental restorations. Such information would help examine causality and the possibility that unmeasured confounders (e.g., dietary factors) affected the results. Despite the limitations, the results of the study add to a small, but growing, body of knowledge on BPA exposure from dental materials and potential related safety issues.1,5–16 A recent biomonitoring study in adults found that new placement of resin-based composite restorations was associated with increases of BPA and other related compounds in saliva within 1 hr after restoration placement and an increased concentration of BPA in urine 9–30 h after restoration placement.8,15 Regarding health outcomes, a randomized clinical trial of the safety of amalgam restorations in children found that higher treatment level with composite restorations containing bisGMA was associated with impaired psychosocial function and increased behavior problems,6,14 certain neuropsychological measures,13 and, possibly, certain immune function markers.11 However, no associations were observed between sealants or other flowable composite dental materials and psychosocial or neuropsychological health or physical development,12 and the study did not include biomonitoring for BPA exposure levels. Thus, it remains uncertain the extent to which dental materials lead to BPA exposure, and if so, whether this exposure has adverse health effects. Longitudinal studies are needed to examine children’s exposure to BPA before and after placement of dental sealants and composite restorations. As dental materials undergo normal wear and tear, repeated measures of BPA levels, over the life of the sealant or restoration, are important to obtain knowledge on the long-term leaching of components and children’s exposure levels. That information, together with high-quality studies of the longterm health effects of low-dose BPA in children and adults, is necessary to conduct an adequate safety and benefit-risk assessment. Thus, although the study by McKinney and colleagues does not provide conclusive evidence on this issue, dentists should be aware of research in this area and stay apprised as new evidence becomes available.
REFERENCES 1. Fleisch AF, Sheffield PE, Chinn C, Edelstein BL, Landrigan PJ. Bisphenol A and related compounds in dental materials. Pediatrics 2010;126(4):760-8.
201
JOURNAL OF EVIDENCE-BASED DENTAL PRACTICE 2. Rochester JR. Bisphenol A and human health: a review of the literature. Reprod Toxicol 2013;42:132-55. 3. Vandenberg LN, Colborn T, Hayes TB, et al. Hormones and endocrine-disrupting chemicals: low-dose effects and nonmonotonic dose responses. Endocr Rev 2012;33(3):378-455. 4. Vandenberg LN, Chahoud I, Padmanabhan V, Paumgartten FJ, Schoenfelder G. Biomonitoring studies should be used by regulatory agencies to assess human exposure levels and safety of bisphenol A. Environ Health Perspect 2010;118(8):1051-4. 5. Van Landuyt KL, Nawrot T, Geebelen B, et al. How much do resinbased dental materials release? A meta-analytical approach. Dent Mater 2011;27(8):723-47. 6. Bellinger DC, Trachtenberg F, Zhang A, Tavares M, Daniel D, McKinlay S. Dental amalgam and psychosocial status: the New England Children’s Amalgam Trial. J Dent Res 2008;87(5):470-4. 7. Joskow R, Barr DB, Barr JR, Calafat AM, Needham LL, Rubin C. Exposure to bisphenol A from bis-glycidyl dimethacrylate-based dental sealants. J Am Dent Assoc 2006;137(3):353-62. 8. Kingman A, Hyman J, Masten SA, et al. Bisphenol A and other compounds in human saliva and urine associated with the placement of composite restorations. J Am Dent Assoc 2012;143(12):1292-302. 9. Martin MD, Bajet D, Woods JS, Dills RL, Poulten EJ. Detection of dental composite and sealant resin components in urine. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2005;99(4):429. 10. Maserejian NN, Hauser R, Tavares M, Trachtenberg FL, Shrader P, McKinlay S. Dental composites and amalgam and physical development in children. J Dent Res 2012;91(11):1019-25.
202
11. Maserejian NN, Shrader P, Brown OA, et al. Dental sealants and composite restorations and longitudinal changes in immune function markers in children. Int J Paediatr Dent 2014;24(3):215-25. 12. Maserejian NN, Shrader P, Trachtenberg FL, Hauser R, Bellinger DC, Tavares M. Dental sealants and flowable composite restorations and psychosocial, neuropsychological, and physical development in children. Pediatr Dent 2014;36(1):68-75. 13. Maserejian NN, Trachtenberg FL, Hauser R, McKinlay S, Shrader P, Bellinger DC. Dental composite restorations and neuropsychological development in children: treatment level analysis from a randomized clinical trial. Neurotoxicology 2012;33(5):1291-7. 14. Maserejian NN, Trachtenberg FL, Hauser R, et al. Dental composite restorations and psychosocial function in children. Pediatrics 2012;130(2):e328-38. 15. Akeroyd JM, Maserejian NN. Composite restorations may lead to increased concentrations of salivary and urinary BPA. J Evid Based Dent Pract 2013;13(2):64-6. 16. Trachtenberg FL, Shrader P, Barregard L, Maserejian NN. Dental composite materials and renal function in children. Br Dent J 2014;216(2):E4.
REVIEWER Nancy Maserejian, ScD Oral Health Policy and Epidemiology, Harvard School of Dental Medicine, 188 Longwood Ave., Boston, MA 02115, USA [email protected]
December 2014
ARTICLE ANALYSIS & EVALUATION ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION Dental sealants and restorations and urinary bisphenol A concentrations in children in the 2003-2004 National Health and Nutrition Examination Survey. McKinney C, Rue T, Sathyanarayana S, Martin M, Seminario AL, DeRouen T. J Am Dent Assoc 2014;145(7):745-750.
REVIEWER Nancy Maserejian, ScD
PURPOSE/QUESTION Is there an association between dental sealants or restorations and urinary bisphenol A levels in schoolaged children in the United States?
SOURCE OF FUNDING None reported
TYPE OF STUDY/DESIGN Cross-sectional study
Possible Association Between Dental Sealants and Urinary Bisphenol A Levels in Children Warrants Additional Biomonitoring and Safety Research SUMMARY Subjects The data came from 1001 children age 6 to 19 years in the United States who participated in the National Health and Nutrition Examination Survey (NHANES) 2003–2004 survey. To be included in the analysis, children had to be part of the random subsample undergoing urinary bisphenol A (BPA) measurement and have data on the number of dental sealants or restorations present at the time of the survey. Children in this analysis were diverse in race/ethnicity (59% white, 19% Mexican-American, 9% black, 5% Hispanic, and 8% other race/ethnicity), sex (56% male, 44% female), and socioeconomic status.
Key Risk/Study Factor The key study factor was the number of occlusal-surface sealants observed at the dental examination. Children were grouped based on number of sealants present: 0, 1–3, 4–6, and 7–16 (the maximum observed). Sealants were present in 33.9% of the children, with 6.4% of all children having seven or more sealants present. The observed number of sealants was counted separately from the observed number of restorations used for caries treatment; 50.0% of the children had at least one restoration present, with 21.3% of all children having seven or more restorations. No data on the type of dental materials used (e.g., composite type, amalgam, or manufacturers) were available.
Main Outcome Measure LEVEL OF EVIDENCE Level 3: Other evidence
STRENGTH OF RECOMMENDATION GRADE Not applicable
J Evid Base Dent Pract 2014;14:200-202 1532-3382/$36.00 Ó 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jebdp.2014.10.009
The main outcome measure was urinary BPA levels (ng/mL), analyzed as part of the NHANES study. The authors categorized urinary BPA into quartiles, based on the distribution of values in the sample of 6- to 19-year-olds in the analysis. When analyzed as a continuous number, the authors used geometric means of log-transformed values of BPA level.
Main Results Compared to children with no sealants, children with 7 to 16 sealants had 25% higher mean urinary BPA levels (95% confidence interval: 14%, 82%; P = 0.23). The geometric means in the highest and lowest categories of sealants were 4.34 and 3.54 ng/mL, respectively. An increase of 10 sealants was associated with an increase in mean urinary BPA concentration of 11% (95% confidence interval: 18%, 52%). These findings were adjusted for the potential confounding variables of age, sex, body mass index, parental education level, race/ethnicity, urinary creatinine levels, and serum cotinine concentrations.
Conclusions Although not statistically significant, the direction of the association between sealants and urinary BPA was in line with the hypothesis, i.e.,
JOURNAL OF EVIDENCE-BASED DENTAL PRACTICE
indicating higher urinary BPA concentrations with greater number of sealants. The authors conclude that the study does not provide strong evidence either to refute or support the notion that composite dental materials lead to BPA exposure, and additional studies are necessary to examine the association over time.
COMMENTARY AND ANALYSIS BPA is used in the manufacture of many polycarbonate plastic products and epoxy resins, including resins such as bisGMA that are used in some dental composite materials.1,2 BPA is a known endocrine disruptor, and adverse biological effects have been observed with low doses in laboratory experiments.3 The adverse effects reach broadly, affecting reproductive health (e.g., reduced ovarian response, miscarriage, premature delivery, reduce male sexual function, reduced sperm quality), immune function, liver function, renal function, and cardiovascular disease parameters.2 Epidemiological studies suggest that chronic low-dose BPA exposure is associated with health problems in children and adults,2 but additional research is needed to test whether these associations are truly causal. In addition, more human biomonitoring studies are needed to increase knowledge on the safety of BPA at various exposure levels and from various exposure sources and to allow fully informed risk assessments.4 Rather than conduct a new biomonitoring study, McKinney and colleagues used available data, collected as part of the NHANES 2003–2004, to examine the association between dental sealants and urinary BPA in children. The directions of the observed associations were in accordance with the hypothesis that dental sealants and restorations are a source of BPA exposure, but the confidence intervals were wide and results were not statistically significant. Therefore it was appropriate that the authors did not make a strong conclusion from the findings and did not suggest changes to clinical practice based on these results. Important limitations of this study include the following: (1) data on type of dental material were not available and (2) the study was a cross-sectional ‘‘snapshot’’ of sealant or restoration status and urinary BPA level. Type of dental material is important because different materials are composed of different resins, some of which have no potential for BPA exposure.5 Furthermore, leaching of dental resins differs across manufacturers.5 For example, if there were truly a measurable association between only a particular sealant subtype and urinary BPA level, this association may be missed in this analysis because the analysis had to combine all dental sealants together. For restorations in particular, this is problematic, given the vast variety of materials used in the United States (e.g., amalgam, glass ionomers, and composites using various materials such as bisGMA, UDMA, ormocer, or silorane). If it were known that Volume 14, Number 4
certain geographic or socioeconomic subgroups are more likely to use traditional composite restorations, it would have been helpful to conduct additional analysis within those subgroups (e.g., stratify analysis by high or low socioeconomic status) to possibly minimize variation in restoration type and confounding by socioeconomic predictors of BPA level. In addition, because the study was cross-sectional, it is unknown if urinary BPA levels increased after the placement of dental restorations. Such information would help examine causality and the possibility that unmeasured confounders (e.g., dietary factors) affected the results. Despite the limitations, the results of the study add to a small, but growing, body of knowledge on BPA exposure from dental materials and potential related safety issues.1,5–16 A recent biomonitoring study in adults found that new placement of resin-based composite restorations was associated with increases of BPA and other related compounds in saliva within 1 hr after restoration placement and an increased concentration of BPA in urine 9–30 h after restoration placement.8,15 Regarding health outcomes, a randomized clinical trial of the safety of amalgam restorations in children found that higher treatment level with composite restorations containing bisGMA was associated with impaired psychosocial function and increased behavior problems,6,14 certain neuropsychological measures,13 and, possibly, certain immune function markers.11 However, no associations were observed between sealants or other flowable composite dental materials and psychosocial or neuropsychological health or physical development,12 and the study did not include biomonitoring for BPA exposure levels. Thus, it remains uncertain the extent to which dental materials lead to BPA exposure, and if so, whether this exposure has adverse health effects. Longitudinal studies are needed to examine children’s exposure to BPA before and after placement of dental sealants and composite restorations. As dental materials undergo normal wear and tear, repeated measures of BPA levels, over the life of the sealant or restoration, are important to obtain knowledge on the long-term leaching of components and children’s exposure levels. That information, together with high-quality studies of the longterm health effects of low-dose BPA in children and adults, is necessary to conduct an adequate safety and benefit-risk assessment. Thus, although the study by McKinney and colleagues does not provide conclusive evidence on this issue, dentists should be aware of research in this area and stay apprised as new evidence becomes available.
REFERENCES 1. Fleisch AF, Sheffield PE, Chinn C, Edelstein BL, Landrigan PJ. Bisphenol A and related compounds in dental materials. Pediatrics 2010;126(4):760-8.
201
JOURNAL OF EVIDENCE-BASED DENTAL PRACTICE 2. Rochester JR. Bisphenol A and human health: a review of the literature. Reprod Toxicol 2013;42:132-55. 3. Vandenberg LN, Colborn T, Hayes TB, et al. Hormones and endocrine-disrupting chemicals: low-dose effects and nonmonotonic dose responses. Endocr Rev 2012;33(3):378-455. 4. Vandenberg LN, Chahoud I, Padmanabhan V, Paumgartten FJ, Schoenfelder G. Biomonitoring studies should be used by regulatory agencies to assess human exposure levels and safety of bisphenol A. Environ Health Perspect 2010;118(8):1051-4. 5. Van Landuyt KL, Nawrot T, Geebelen B, et al. How much do resinbased dental materials release? A meta-analytical approach. Dent Mater 2011;27(8):723-47. 6. Bellinger DC, Trachtenberg F, Zhang A, Tavares M, Daniel D, McKinlay S. Dental amalgam and psychosocial status: the New England Children’s Amalgam Trial. J Dent Res 2008;87(5):470-4. 7. Joskow R, Barr DB, Barr JR, Calafat AM, Needham LL, Rubin C. Exposure to bisphenol A from bis-glycidyl dimethacrylate-based dental sealants. J Am Dent Assoc 2006;137(3):353-62. 8. Kingman A, Hyman J, Masten SA, et al. Bisphenol A and other compounds in human saliva and urine associated with the placement of composite restorations. J Am Dent Assoc 2012;143(12):1292-302. 9. Martin MD, Bajet D, Woods JS, Dills RL, Poulten EJ. Detection of dental composite and sealant resin components in urine. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2005;99(4):429. 10. Maserejian NN, Hauser R, Tavares M, Trachtenberg FL, Shrader P, McKinlay S. Dental composites and amalgam and physical development in children. J Dent Res 2012;91(11):1019-25.
202
11. Maserejian NN, Shrader P, Brown OA, et al. Dental sealants and composite restorations and longitudinal changes in immune function markers in children. Int J Paediatr Dent 2014;24(3):215-25. 12. Maserejian NN, Shrader P, Trachtenberg FL, Hauser R, Bellinger DC, Tavares M. Dental sealants and flowable composite restorations and psychosocial, neuropsychological, and physical development in children. Pediatr Dent 2014;36(1):68-75. 13. Maserejian NN, Trachtenberg FL, Hauser R, McKinlay S, Shrader P, Bellinger DC. Dental composite restorations and neuropsychological development in children: treatment level analysis from a randomized clinical trial. Neurotoxicology 2012;33(5):1291-7. 14. Maserejian NN, Trachtenberg FL, Hauser R, et al. Dental composite restorations and psychosocial function in children. Pediatrics 2012;130(2):e328-38. 15. Akeroyd JM, Maserejian NN. Composite restorations may lead to increased concentrations of salivary and urinary BPA. J Evid Based Dent Pract 2013;13(2):64-6. 16. Trachtenberg FL, Shrader P, Barregard L, Maserejian NN. Dental composite materials and renal function in children. Br Dent J 2014;216(2):E4.
REVIEWER Nancy Maserejian, ScD Oral Health Policy and Epidemiology, Harvard School of Dental Medicine, 188 Longwood Ave., Boston, MA 02115, USA [email protected]
December 2014