Correspondence/Rebuttal pubs.acs.org/est
Response to Comment on “New Look at BTEX: Are Ambient Levels a Problem?”
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response, internal validity, and consistency of the effect across different populations could not be completed. In the case of the preterm birth finding, the fact that this was the only study showing an association does not negate the existence of a possible relationship (as Lynch implies). Our search did not reveal negative studies that contradicted that finding, nor did a recent evaluation of the noncancer effects of benzene published in 2014.9 Of course, publication bias may be a factor but more than one study is needed to use statistical tools to assess publication bias. Further, with such a high profile chemical like benzene, we would expect that studies with null findings would be published, as was the case with several of the other end points referenced in our review.10−18 The central issue here is that the BTEX compounds have not been thoroughly studied in this context (i.e., at ambient levels and noncancer end points). In the absence of a consistent null effect, the potential for effects from low exposure concentrations, combined with a lack of controlled experiments reflecting BTEX exposure scenarios in the general population, our recommendations pointed to a need for future research. We used our analysis of study quality (i.e., risk of bias) of individual studies to point out specific areas that needed improvement. Recommendations included using better measures of exposure, exploring critical life stages, and determining the mechanistic basis for the observed effects. Research that addresses these weaknesses, and fills knowledge gaps with regards to specific end points identified in our review, would create the scenario necessary to conduct an SR. Further, a deeper understanding of the potential health effects posed by low level BTEX exposure, gained through well conducted research to drive evidence based conclusions, would assist policy-makers in their decisions regarding the public health risks of continued BTEX exposure.
n a comment submitted to Environmental Science and Technology, Lynch critiques an article we published in April 2015 presenting the epidemiological literature that evaluated the noncancer health impacts of nonoccupational exposure to benzene, toluene, ethylbenzene, and xylenes (BTEX).1,2 Lynch argues that a rigorous systematic review (SR) of the association between ambient level BTEX exposure and endocrine effects is needed, and we agree. In fact, knowing that the body of evidence for this broad topic (four individual chemicals and the mixture, and multiple end points) was sparse, the goal of our review was to identify areas where research was needed in order to be able to conduct such an assessment. Our paper was not an SR, which is an in-depth assessment of a single specific end point (e.g., birth weight or preterm birth) and requires enough studies to assess confidence in the body of evidence, to employ tools to thoroughly evaluate heterogeneity as needed, and to accurately estimate the effect size, especially if the magnitude of the effect is small yet practically or medically relevant.3−6 Our review was similar to a scoping review, which can be used to explore the breadth of research activity, summarize and convey research findings, identify research gaps, and determine the usefulness of undertaking an SR.7,8 Our assessment indicated that asthma was an end point that may be suitable for SR, due to having a sufficient number of studies on a single end point. However, while the measures of the disease appear to be similar (e.g., asthma vs exercise induced asthma) an expert evaluation might find them to be too disparate to combine in a single meta-analysis (MA). Further in some instances using techniques like meta-regression or other complex MA tools might not be feasible due to a low number of studies.3 Our evaluation also indicated that as a whole, the body of evidence suggested endocrine mechanisms potentially underlie many of the conditions connected to BTEX exposure. This is important because these compounds have typically only been evaluated as potential carcinogens and a targeted effort to fill these mechanistic research gaps would help in determining the relationship, if any, between BTEX exposure and health effects. These efforts would improve our understanding of the endocrine disrupting potential of BTEX and provide a body of evidence sufficient to conduct future SRs on endocrine relevant end points. Lynch also pointed out inconsistent results across the body of evidence assessing developmental effects from maternal exposure to benzene.2 It is true that these inconsistencies could be addressed by using MA. However, the small literature base (1−2 studies per specific end point) hinders the adequate reconciliation of results across studies and precludes an accurate estimate of the effect sizes. Additionally, because several different measures of development (e.g., biparietal diameter, birth weight, preterm birth, head circumference, and spina bifida) using different units of measure were evaluated, combining these in a single MA would not be appropriate or feasible. Similarly, other cumulative study features such as dose © XXXX American Chemical Society
Ashley L. Bolden* Carol F. Kwiatkowski
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The Endocrine Disruption Exchange (TEDX), Paonia, Colorado 81428, United States
AUTHOR INFORMATION
Corresponding Author
*Phone/fax: 970-527-4082; e-mail: ashley.bolden@colorado. edu. Notes
The authors declare no competing financial interest.
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REFERENCES
(1) Bolden, A. L.; Kwiatkowski, C. F.; Colborn, T. New Look at BTEX: Are Ambient Levels a Problem? Environ. Sci. Technol. 2015, 49 (9), 5261−5276.
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DOI: 10.1021/acs.est.5b06048 Environ. Sci. Technol. XXXX, XXX, XXX−XXX
Environmental Science & Technology
Correspondence/Rebuttal
(2) Lynch, A. M. Comment on “New Look at BTEX: Are Ambient Levels a Problem?” Environ. Sci. Technol. 2015, 10.1021/ acs.est.5b05286. (3) Borenstein, M.; Hedges, L. V.; Higgins, J. P. T.; Rothstein, H. R. Introduction to Meta-Analysis; Wiley: 2011. (4) Hedges, L. V.; Pigott, T. D. The power of statistical tests in metaanalysis. Psychological methods 2001, 6 (3), 203. (5) Rooney, A. A.; Boyles, A. L.; Wolfe, M. S.; Bucher, J. R.; Thayer, K. A. Systematic Review and Evidence Integration for Literature-Based Environmental Health Science Assessments. Environ. Health Perspect 2014, 122 (7), 711−718. (6) Handbook for Conducting a Literature-Based Health Assessment Using OHAT Approach for Systematic Review and Evidence Integration; Office of Health Assessment and Translation, 2015; https://ntp.niehs. nih.gov/ntp/ohat/pubs/handbookjan2015_508.pdf. (7) Arksey, H.; O’Malley, L. Scoping studies: towards a methodological framework. International journal of social research methodology 2005, 8 (1), 19−32. (8) Levac, D.; Colquhoun, H.; O’Brien, K. K. Scoping studies: advancing the methodology. Implement Sci. 2010, 5 (1), 1−9. (9) Bahadar, H.; Mostafalou, S.; Abdollahi, M. Current understandings and perspectives on non-cancer health effects of benzene: a global concern. Toxicol. Appl. Pharmacol. 2014, 276 (2), 83−94. (10) Estarlich, M.; Ballester, F.; Aguilera, I.; Fernandez-Somoano, A.; Lertxundi, A.; Llop, S.; Freire, C.; Tardon, A.; Basterrechea, M.; Sunyer, J.; Iniguez, C. Residential exposure to outdoor air pollution during pregnancy and anthropometric measures at birth in a multicenter cohort in Spain. Environ. Health Perspect 2011, 119 (9), 1333−1338. (11) Bentayeb, M.; Helmer, C.; Raherison, C.; Dartigues, J. F.; Tessier, J. F.; Annesi-Maesano, I. Bronchitis-like symptoms and proximity air pollution in French elderly. Respir Med. 2010, 104 (6), 880−888. (12) Billionnet, C.; Gay, E.; Kirchner, S.; Leynaert, B.; AnnesiMaesano, I. Quantitative assessments of indoor air pollution and respiratory health in a population-based sample of French dwellings. Environ. Res. 2011, 111 (3), 425−434. (13) Hirsch, T.; Weiland, S. K.; von Mutius, E.; Safeca, A. F.; Grafe, H.; Csaplovics, E.; Duhme, H.; Keil, U.; Leupold, W. Inner city air pollution and respiratory health and atopy in children. Eur. Respir. J. 1999, 14 (3), 669−677. (14) Hulin, M.; Caillaud, D.; Annesi-Maesano, I. Indoor air pollution and childhood asthma: variations between urban and rural areas. Indoor Air 2010, 20 (6), 502−514. (15) Gordian, M. E.; Stewart, A. W.; Morris, S. S. Evaporative gasoline emissions and asthma symptoms. Int. J. Environ. Res. Public Health 2010, 7 (8), 3051−3062. (16) Rive, S.; Hulin, M.; Baiz, N.; Hassani, Y.; Kigninlman, H.; Toloba, Y.; Caillaud, D.; Annesi-Maesano, I. Urinary S-PMA related to indoor benzene and asthma in children. Inhalation Toxicol. 2013, 25 (7), 373−382. (17) Smargiassi, A.; Goldberg, M. S.; Wheeler, A. J.; Plante, C.; Valois, M. F.; Mallach, G.; Kauri, L. M.; Shutt, R.; Bartlett, S.; Raphoz, M.; Liu, L. Associations between personal exposure to air pollutants and lung function tests and cardiovascular indices among children with asthma living near an industrial complex and petroleum refineries. Environ. Res. 2014, 132, 38−45. (18) Zhou, C.; Baiz, N.; Banerjee, S.; Charpin, D. A.; Caillaud, D.; de Blay, F.; Raherison, C.; Lavaud, F.; Annesi-Maesano, I. The relationships between ambient air pollutants and childhood asthma and eczema are modified by emotion and conduct problems. Ann. Epidemiol 2013, 23 (12), 778−783.
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DOI: 10.1021/acs.est.5b06048 Environ. Sci. Technol. XXXX, XXX, XXX−XXX
