Next Article in Journal
Revitalization of Total Petroleum Hydrocarbon Contaminated Soil Remediated by Landfarming
Next Article in Special Issue
Do Neighborhood Factors Modify the Effects of Lead Exposure on Child Behavior?
Previous Article in Journal
Characteristics of PM2.5 and Its Correlation with Feed, Manure and NH3 in a Pig-Fattening House
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Toxics
Volume 10
Issue 3
10.3390/toxics10030146
toxics-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Exposure to Endocrine Disrupting Chemicals in Canada: Population-Based Estimates of Disease Burden and Economic Costs

by
Julia Malits
1,*,
Mrudula Naidu
2 and
Leonardo Trasande
2,3,4,5,6
1
Harvard Medical School, Boston, MA 02115, USA
2
Department of Pediatrics, NYU School of Medicine, New York, NY 10016, USA
3
Department of Environmental Medicine, NYU School of Medicine, New York, NY 10016, USA
4
Department of Population Health, NYU School of Medicine, New York, NY 10016, USA
5
NYU Wagner School of Public Service, New York, NY 10012, USA
6
NYU School of Global Public Health, New York, NY 10003, USA
*
Author to whom correspondence should be addressed.
Toxics 2022, 10(3), 146; https://doi.org/10.3390/toxics10030146
Submission received: 25 January 2022 / Revised: 23 February 2022 / Accepted: 3 March 2022 / Published: 19 March 2022
(This article belongs to the Special Issue Interaction and Intersection: The Effects of Environmental Exposures on Children's Health)
Versions Notes

Abstract

:
Exposure to endocrine-disrupting chemicals (EDCs) contributes to substantial disease burden worldwide. We aim to quantify the disease burden and costs of EDC exposure in Canada and to compare these results with previously published findings in the European Union (EU) and United States (US). EDC biomonitoring data from the Canadian Health Measures Survey (2007–2011) was applied to 15 exposure–response relationships, and population and cost estimates were based on the 2010 general Canadian population. EDC exposure in Canada (CAD 24.6 billion) resulted in substantially lower costs than the US (USD 340 billion) and EU (USD 217 billion). Nonetheless, our findings suggest that EDC exposure contributes to substantial and costly disease burden in Canada, amounting to 1.25% of the annual Canadian gross domestic product. As in the US, exposure to polybrominated diphenyl ethers was the greatest contributor of costs (8.8 billion for 374,395 lost IQ points and 2.6 billion for 1610 cases of intellectual disability). In the EU, organophosphate pesticides were the largest contributor to costs (USD 121 billion). While the burden of EDC exposure is greater in the US and EU, there remains a similar need for stronger EDC regulatory action in Canada beyond the current framework of the Canadian Environmental Protection Act of 1999.

1. Introduction

In the past several decades, international efforts to improve our understanding of the adverse health outcomes of exposure to endocrine disrupting chemicals (EDCs) have markedly expanded [1]. A growing body of literature continues to document the varied and harmful effects that many widely used man-made chemicals have upon the endocrine system [2,3]. Even more so, low-income and marginalized communities are known to be disproportionately exposed to such chemicals [4,5].
In its first of two scientific statements, the Endocrine Society submitted that “from a physiological perspective, an endocrine-disrupting substance is a compound, either natural or synthetic, which, through environmental or inappropriate developmental exposures, alters the hormonal and homeostatic systems that enable the organism to communicate with and respond to its environment” [6]. EDCs encompass many substances, including polychlorinated biphenyls, polybrominated diphenyl ethers, dioxins, bisphenols, phthalates, among others. They are used for a range of purposes, such as industrial solvents and lubricants, plastics, plasticizers, pesticides and pharmaceutical agents. 6 Adverse health outcomes associated with exposure to EDCs include, but are not limited to, testicular and breast cancer, infertility, male and female reproductive dysfunction, birth defects, obesity, diabetes, cardiovascular and pulmonary disease, as well as neurobehavioral disorders [7]. Recent studies provide an overview of the mechanisms of action of EDCs, which include inhibitory or stimulatory binding to a hormone receptor, stimulation or inhibition of endogenous hormone production or hormone receptor expression or epigenetic effects, all of which may lead to a disruption in the endocrine system [3,8].
Previously published studies by our group have quantified the disease burden and economic costs associated with EDCs in the European Union (EU) and United States (US). The authors examined EDCs (polybrominated diphenyl ethers (PBDE), organophosphate pesticides (OP), dichlorodipheyldichloroethylene (DDE), bisphenol A (BPA), and phthalates) and associated health outcomes for which a steering committee of experts found robust toxicological and epidemiologic evidence [9]. Our group found that EDCs amounted to USD 217 billion (1.28% of gross domestic product, GDP) in the EU and USD 340 billion in the US (2.33% of GDP) [9,10]. In Canada, the epidemiologic literature evaluating the disease burden of environmental chemicals, including EDCs, is growing [11]. Eykelbosh and colleagues (2018) provide a systematic review of recent studies evaluating exposure to environmental chemicals in the general Canadian population using data from the Canadian Health Measures Survey (CHMS). For example, Do and colleagues (2017) applied the CHMS to demonstrate a positive association between bisphenol A (BPA) exposure and obesity in Canada, an association that has been widely corroborated by other studies [12,13]. However, there is limited evidence of the economic costs due to the EDC-attributable disease burden in Canada.
The principal regulatory framework for environmental substances, including EDCs, is the Canadian Environmental Protection Act (CEPA) of 1999, though there is no explicit mention of EDCs. To manage EDC exposure, both the US and Canada apply a risk-based approach. In contrast, the EU applies the precautionary principle in its approach to regulating EDCs and other environmental chemicals [4]. This analysis is the most comprehensive study to date documenting the disease burden and economic costs associated with exposure to multiple EDCs in the general Canadian population. The aim of this study is to quantify the disease burden and economic costs associated with exposure to EDCs in Canada, and to place our findings in the context of previously published studies in the US and EU.

2. Materials and Methods

2.1. Study Design

This study was designed in parallel to our previous publications investigating population-based estimates of EDC—attributable disease burden in the EU and US. We applied the ranges for probabilities of causation put forth by expert panels established by the Endocrine Society intended to assess the disease burden and economic costs attributable to exposure to EDCs in Europe [9]. The probabilities were determined based on available laboratory and epidemiological evidence, the strength of which was appraised using the Danish Environmental Protection Agency criteria and the GRADE Working Group criteria, respectively [14,15]. A scientific steering committee adapted the approach developed by the Intergovernmental Panel on Climate Change (IPCC, Geneva, Switzerland) to generate probabilities of causation based on the strength of the laboratory and epidemiological evidence [16].
The laboratory and toxicological evidence pertained to 15 exposure–response relationships between EDCs and various diseases. The EDCs evaluated were polybrominated diphenyl ethers (PBDE), organophosphate pesticides (OP), dichlorodipheyldichloroethylene (DDE), bisphenol A (BPA), phthalates (di-2-ethylhexylphthalate (DEHP), benzylphthalates, butylphthaltes) and combinations of these chemicals (see Supplementary Materials). The categories for health outcomes were neurodevelopmental dysfunction (loss of intelligence quotient points and resultant intellectual disability, attention deficit hyperactivity disorder, autism), metabolic disorders (adult and childhood obesity, adult diabetes), male reproductive disorders (cryptorchidism, testicular cancer, infertility, early cardiovascular mortality due to decreased testosterone levels) and female reproductive disorders (leiomyomas and endometriosis).
To estimate the cost of disease burden attributable to environmental exposures, we applied a model used by the Institute of Medicine [17], as we had in our EU and US studies. The model is as follows:
Attributable disease burden = increment in disease × attributable fraction × population size.
Attributable cost = increment in disease × attributable fraction × population size x cost per increment.
The attributable fraction (AF) of a risk factor is defined as the proportional decrease in the number of cases of morbidity or mortality resulting from a decrease in the risk factor [18]. The AF can be quantified by the equation:
Attributable   fraction = prevalence exposure × ( RR − 1 ) 1 + ( prevalence exposure × ( RR − 1 ) )
where relative risk (RR) is the relative risk of morbidity associated with a particular exposure.

2.2. Data Collection and Measurements

To create estimates comparable to those for our EU and US studies, we obtained nationally representative human biomonitoring data from the CHMS, which is jointly overseen by Statistics Canada, Health Canada and the Public Health Agency of Canada. CHMS has been continuously administered since 2007 in two-year cycles. Further information about CHMS has been documented extensively by Haines and colleagues (2017) [19]. When biomonitoring data for specific substances was not included in CHMS, we applied data from the National Health and Nutrition Examination Surveys (NHANES) to extrapolate the expected levels in the general Canadian population based on the appropriate ratios of chemicals. NHANES is a nationally representative, multicomponent survey of the non-institutionalized US population that is administered biennially by the National Centers for Health Statistics of the Centers for Disease Control and Prevention. Further, when specific percentiles were missing from the dataset, we interpolated the appropriate exposure level.
Data for PBDE, OP and DDE was extracted from the 2007–2009 survey cycles, and from the 2009–2011 survey cycles for BPA and phthalates. Values for all chemicals were separated into percentile ranges: 0–9th, 10th–24th, 25th–49th, 50th–75th, 75th–89th, and 90th–99th. The lowest quintile was assumed to have no exposure, and the remaining percentiles were assumed to have levels of exposure corresponding to their respective lowest extreme (i.e., 10th percentile of exposure for all individuals in the 10th–24th percentile grouping). Census data for the Canadian population, stratified by gender and age, was obtained from the Census Program, coordinated by Statistics Canada every five years [20]. We applied census data from 2010 with one exception (women married or living in common law in 2011 for phthalate-associated increases in assisted reproductive technology).

2.3. Exposure-Response Relationships

We considered four ERRs relating to neurobehavioral dysfunction (PBDE and intellectual quotient (IQ) point loss and intellectual disability (ID), OP and IQ point loss and ID, multiple exposures (OP and PBDE) and ADHD, phthalates and autism); five ERRs related to metabolic dysfunction (DDE and childhood obesity, DDE and adult diabetes, DEHP and adult obesity, DEHP and adult diabetes, BPA and childhood obesity); three ERRs related to male reproductive dysfunction (PBDE and testicular cancer, PBDE and cryptorchidism, phthalates and male infertility resulting in assisted reproductive technology (ART), phthalates and low testosterone resulting in increased early mortality); and two ERRs related to female reproductive dysfunction (DDE and leiomyomas, DEHP and endometriosis). Whenever possible, we applied exposure–response relationships identified by studies focused on EDC exposure levels of the general Canadian population in our base case estimate and sensitivity analysis. When Canadian studies were unavailable in the literature, we used the exposure–response relationships previously applied in the EU and US studies. Our methodological approach for each exposure–response relationship is discussed in detail in the Supplementary Materials.

2.4. Estimates of Economic Costs

We estimated total economic costs for each disease by applying a cost-of-illness approach for both direct costs and indirect costs [21]. Similar to our US study, we followed previously published guidelines by the Panel on Cost Effectiveness and Medicine [22]. We applied Canadian data sources and published cost estimates whenever possible for base case estimates, as well as low-end and high-end estimates, in our sensitivity analysis. When Canadian estimates were unavailable, we used data from NHANES and the cost estimates previously applied to our US study. Overall costs were generated by applying the disease incidence or prevalence and the size of the at-risk population. All economic costs were adjusted to the 2010 Canadian dollar year using the medical care consumer price index [23], and converted from the US to Canadian dollar using purchasing power parities (PPP) [24]. A detailed summary of the publications used for cost estimates may be found in the Supplementary Materials.

2.5. Statistical Analysis

We performed a descriptive analysis using Microsoft Excel and Stata 14.1. When biomonitoring data from NHANES was applied to extrapolate phthalate values in the Canadian general population, the appropriate environmental sample weights for subsamples were incorporated for the years 2009–2010.

3. Results

A summary of the disease burden and economic costs attributable to EDCs for each exposure–response relationship along with sensitivity analyses is presented in Table 1 and Table 2, respectively. Overall, our findings indicate that the disease burden arising from EDC exposure is substantially lower in the general Canadian population than in either the US or EU.
As in our US study, we found that the greatest burden of disease and economic costs associated with EDC exposure in Canada was neurobehavioral dysfunction resulting from PBDE exposure. Specifically, in utero PBDE exposure was associated with 374,395 lost IQ points and 1610 ID cases, and consequently, $8.8 billion CAD in lost IQ points and $2.6 billion CAD resulting from ID. The second largest contributor to EDC-attributable disease burden was phthalate exposure leading to endometriosis. Exposure to DEHP was associated with 10,151 cases of endometriosis, resulting in $5.7 billion CAD in direct and indirect costs.
Of the $24.6 billion CAD in total costs attributable to EDC exposure in Canada, $11.5 billion resulted from exposure to PBDE, $8.4 billion from phthalates, $4.3 billion from organophosphate pesticides, $391 million from DDE, and $59 million from BPA. Of all adverse health outcomes attributable to EDC exposure, neurobehavioral dysfunction accounted for $15.9 billion, metabolic disorders (diabetes and obesity) in children and adults accounted for $1.2 billion, male reproductive disorders (testicular cancer, cryptorchidism and infertility leading to use of assisted reproductive technology) accounted for $30.1 million, early mortality associated with decreased testosterone levels accounted for $1.8 billion, and female reproductive disorders (endometriosis and uterine fibroids) accounted for $5.7 billion.
A comparison of our findings in the US, EU and Canada is presented in Table 3. The most notable trend in Table 3 is that the disease burden and associated costs of EDC exposure are substantially more extensive in the US and EU than in Canada for all exposure–response relationships considered in this study. In our initial study evaluating EDC-attributable disease burden in the EU, we found that exposure to organophosphate pesticides resulted in the greatest number of cases and associated costs. In the US, however, our analysis revealed that exposure to PBDE played the largest role in EDC-attributable disease burden and associated costs.

4. Discussion

In our analysis, the costs of exposure to EDCs among the general Canadian population amounted to $24.6 billion (CAD 2010). This amounts to 1.25% of the Canadian GDP in 2010 or $724 CAD per capita [26]. In contrast, EDC exposure was associated with $340 billion USD in the US (2.33% of US GDP) and $217 billion USD in the EU (1.28% of EU GDP). The main driver of costs associated with EDC exposure in Canada was PBDE-associated IQ loss and intellectual disability (ID), resulting in $11.5 billion CAD, or $276.5 USD per capita in Canada. This is three times lower than PBDE-associated IQ loss and ID in the US, which amounted to $266 billion USD or $860 USD per capita. PBDE-associated IQ loss and ID in the EU, with $12.6 billion USD in economic costs or $28.5 USD per capita, were much lower than in Canada.
Our findings must be understood within the current regulatory environment in Canada regarding EDCs. The differences likely relate to policy differences between North America and Europe, in which restrictions on PBDEs were greater in Europe, especially compared to the US where their use was essentially required to meet a California flammability standard which has since been revised [10]. As in the US, Canada approaches chemical regulation with a risk-based strategy under the Canadian Environmental Protection Act of 1999 [27]. Within CEPA 1999, there is no explicit regulation of EDCs; rather, a risk assessment similar to other synthetic compounds is performed. In comparison, the EU applies the precautionary principle, the more robust and prudent strategic approach [4].
We acknowledge several limitations in this study, some of which are similar to those outlined in our EU and US analyses. We closely followed the rigorous methodology of our prior studies to review and apply the toxicological and epidemiological evidence in this analysis [9,28]. However, we recognize that strong toxicologic and epidemiologic evidence supporting an association between EDC exposure and adverse health outcomes, as well as their underlying pathophysiologic mechanisms, far outweigh expert opinion. Nonetheless, the available literature to date is both robust [8] and speaks to the importance of urgently addressing the disease burden and costs associated with EDC exposure in Canada and globally. This analysis, moreover, excluded Monte Carlo simulations, as the central aim of our study was principally to compare the disease burden and associated costs across several countries. To account for uncertainty in our estimates, Canadian policymakers may multiply the aggregate costs by a factor of 0.8 for each exposure–response relationship.
Further, we recognize that our study focused on evaluating the effects of exposure to a multitude of chemicals individually, rather than the effects of combined exposure to EDCs. While this was not the aim of our study, we emphasize that it remains an important area of ongoing scientific inquiry [29]. Our study likely underestimates the true burden of disease and economic costs to society associated with EDC exposure for at least three reasons. First, our study assessed <5% of all EDCs for which there is adequately robust exposure, toxicological and epidemiological evidence to meet the criteria for inclusion in our analysis [30]. For similar reasons, we only assessed those EDC-associated health outcomes for which there is solid, convincing evidence for causation. There is likely a far larger constellation of diseases and economic costs associated with EDC exposure than is reflected in our study, which may very well underestimate the true economic costs and disease burden borne by the Canadian population [31]. Lastly, our economic estimates reflect both healthcare-associated and indirect (i.e., DALYs) costs that likely do not fully capture the economic toll borne by individuals suffering from the morbidity associated with EDC exposure, including intangible costs to quality of life.
Additionally, we based lifetime costs of chronic diseases on annual cost estimates in certain exposure–response relationships. While this approach is widely performed, we acknowledge that it is an imprecise estimate that would preferably be substituted with robust evidence of lifetime cost estimates if the data were available. Lastly, we recognize that the exposure data applied in this study dates to 2007–2011. While the most recent data would be more practical in guiding public health officials and policy makers in Canada, the timing of our data allows for a ready comparison of EDC exposure, disease burden and economic costs in Canada, the US and EU in the context of their regulatory environments based on our previously published studies. Lastly, it is likely that our analysis underestimates the disease burden and costs associated with more recent EDC exposure as the commercial applications of EDCs continue to rise globally [32].
The urgent public health threat of EDC exposure has been recognized by the Endocrine Society, the WHO and UNEP [7,33]. The gravity of this threat is underscored by evidence to suggest that EDCs have transgenerational effects on human health and well-being, and by extension, the economic health of society [34]. However, when considering alternatives to EDCs in commercial and industrial settings, it is critical to ensure that substitutions are validated to be safe and not simply a “regrettable substitution” [35].
To our knowledge, this study is the first to comprehensively examine multiple EDC exposures, disease burden and economic costs in Canada. Our findings underscore the urgent need to minimize EDC exposure among the general Canadian population to limit the substantial disease burden and economic costs to society, which amount to 1.25% the 2010 Canadian GDP.
We encourage more robust regulatory action that extends beyond CEPA 1999 to specifically and rigorously monitor and limit exposure to EDCs. In 2021, the Canadian federal government considered Bill C-28, which sought to modernize aspects of CEPA for the first time since its creation in 1999 [36]. In short, the bill aimed to modernize the Canadian government’s approach to promoting environmental health by recognizing every Canadian citizen’s right to a safe and healthy environment. The bill would have provided a regulatory framework for a more thorough reviewing of the toxicological and epidemiological evidence of various substances to act upon the available literature in a risk-based manner, and with a particular focus on identifying vulnerable populations. The bill further sought to amend the Food and Drugs Act to include a risk assessment of potentially toxic substances in food, drugs and personal care products—a critical regulatory step as these are substantial sources of human exposure to EDCs. While Bill C-28 stalled in the Fall 2021 parliamentary session, the need to modernize CEPA 1999 remains important. However, the bill did not make explicit mention of EDCs, an omission that we hope will be corrected in subsequent parliamentary sessions that reconsider Bill C-28 or introduce other bills to modernize CEPA 1999. If targeted regulatory steps are not taken, EDC exposure will continue to substantially contribute to disease burden and economic costs across the general Canadian population, especially among vulnerable communities.

Supplementary Materials

The supporting supplementary data can be downloaded at: www.mdpi.com/article/10.3390/toxics10030146/s1. References [37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103] is in the Supplementary Materials.

Author Contributions

Conceptualization, L.T.; methodology, L.T. and J.M.; formal analysis, L.T. and J.M.; investigation, L.T. and J.M.; resources, L.T. and J.M.; data curation, L.T.; writing—original draft preparation, J.M.; writing—review and editing, L.T., J.M. and M.N.; supervision, L.T.; project administration, M.N. and J.M. All authors have read and agreed to the published version of the manuscript.

Funding

Research reported in this publication was supported by the NIEHS of the National Institutes of Health: P2CES033423.

Institutional Review Board Statement

Approval by the Institutional Review Board was not required as this study contained de-identified human data. To document the human subject exemption, the corresponding author completed an attestation form designed by the New York University School of Medicine.

Informed Consent Statement

Not applicable.

Data Availability Statement

Data regarding EDC exposure was obtained from the publicly available Canadian Health Measures Survey.

Acknowledgments

We thank the authors of seven previous studies that had assessed the economic costs of endocrine disrupting chemicals, on which we based this work.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. The International Panel on Chemical Pollution. Overview Report III: Existing National, Regional, and Global Regulatory Frameworks Addressing Endocrine Disrupting Chemicals (EDCs). 2017. Available online: https://wedocs.unep.org/bitstream/handle/20.500.11822/25636/edc_report3.pdf?sequence=1&isAllowed=y (accessed on 1 May 2021).
  2. Herbst, A.L.; Ulfelder, H.; Poskanzer, D.C. Adenocarcinoma of the vagina. Association of maternal stilbestrol therapy with tumor appearance in young women. N. Engl. J. Med. 1971, 284, 878–881. [Google Scholar] [CrossRef] [PubMed]
  3. Schug, T.T.; Janesick, A.; Blumberg, B.; Heindel, J.J. Endocrine Disrupting Chemicals and Disease Susceptibility. J. Steroid Biochem. Mol. Biol. 2011, 127, 204–215. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  4. Kassotis, C.D.; Vandenberg, L.N.; Demeneix, B.A.; Porta, M.; Slama, R.; Trasande, L. Endocrine-disrupting chemicals: Economic, regulatory, and policy implications. Lancet Diabetes Endocrinol. 2020, 8, 719–730. [Google Scholar] [CrossRef]
  5. Ruiz, D.; Becerra, M.; Jagai, J.S.; Ard, K.; Sargis, R.M. Disparities in Environmental Exposures to Endocrine-Disrupting Chemicals and Diabetes Risk in Vulnerable Populations. Diabetes Care 2018, 41, 193–205. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  6. Diamanti-Kandarakis, E.; Bourguignon, J.-P.; Giudice, L.C.; Hauser, R.; Prins, G.S.; Soto, A.M.; Zoeller, R.T.; Gore, A.C. Endocrine-disrupting chemicals: An Endocrine Society scientific statement. Endocr. Rev. 2009, 30, 293–342. [Google Scholar] [CrossRef]
  7. Gore, A.C.; Chappell, V.A.; Fenton, S.E.; Flaws, J.A.; Nadal, A.; Prins, G.S.; Toppari, J.; Zoeller, R.T. EDC-2: The Endocrine Society’s Second Scientific Statement on Endocrine-Disrupting Chemicals. Endocr. Rev. 2015, 36, E1–E150. [Google Scholar] [PubMed]
  8. Combarnous, Y.; Nguyen, T.M.D. Comparative Overview of the Mechanisms of Action of Hormones and Endocrine Disruptor Compounds. Toxics 2019, 7, 5. [Google Scholar] [CrossRef] [Green Version]
  9. Trasande, L.; Zoeller, R.T.; Hass, U.; Kortenkamp, A.; Grandjean, P.; Myers, J.P.; DiGangi, J.; Bellanger, M.; Hauser, R.; Legler, J.; et al. Estimating Burden and Disease Costs of Exposure to Endocrine-Disrupting Chemicals in the European Union. J. Clin. Endocrinol. Metab. 2015, 100, 1245–1255. [Google Scholar] [CrossRef]
  10. Attina, T.M.; Hauser, R.; Sathyanarayana, S.; Hunt, P.A.; Bourguignon, J.-P.; Myers, J.P.; DiGangi, J.; Zoeller, R.T.; Trasande, L. Exposure to endocrine-disrupting chemicals in the USA: A population-based disease burden and cost analysis. Lancet Diabetes Endocrinol. 2016, 4, 996–1003. [Google Scholar] [CrossRef]
  11. Eykelbosh, A.; Werry, K.; Kosatsky, T. Leveraging the Canadian Health Measures Survey for environmental health research. Environ. Int. 2018, 119, 536–543. [Google Scholar] [CrossRef]
  12. Do, M.T.; Chang, V.; Mendez, M.A.; De Groh, M. Urinary bisphenol A and obesity in adults: Results from the Canadian Health Measures Survey. Heal. Promot. Chronic Dis. Prev. Can. 2017, 37, 403–412. [Google Scholar] [CrossRef] [PubMed]
  13. Beausoleil, C.; Emond, C.; Cravedi, J.P.; Antignac, J.P.; Applanat, M.; Appenzeller, B.R.; Beaudouing, R.; Belzuncesh, L.P.; Canivenc-Lavieri, M.-C.; Chevalier, N.; et al. Regulatory identification of BPA as an endocrine disruptor: Context and methodology. Mol. Cell. Endocrinol. 2018, 475, 4–9. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  14. Hass, U.; Christiansen, S.; Axelstad, M.; Boberg, J. Evaluation of 22 SIN List 2.0 Substances according to the Danish Proposal on Criteria for Endocrine Disrupters. 2012. Available online: http://eng.mst.dk/media/mst/67169/SIN%20report%20and%20Annex.pdf (accessed on 1 May 2021).
  15. Schünemann, H.J.; Oxman, A.D.; Brozek, J.; Glasziou, P.; Jaeschke, R.; Vist, G.E.; Williams, J.W., Jr.; Kunz, R.; Craig, J.; Montori, V.M.; et al. Grading quality of evidence and strength of recommendations for diagnostic tests and strategies. BMJ 2008, 336, 1106–1110. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  16. Intergovernmental Panel on Climate Change. Guidance Notes for Lead Authors of the IPCC Fourth Assessment Report on Addressing Uncertainties. 2005. Available online: http://www.ipcc.ch/meetings/ar4-workshops-express-meetings/uncertainty-guidance-note.pdf (accessed on 1 May 2021).
  17. Institute of Medicine. Costs of Environment-Related Health Effects: A Plan for Continuing Study; National Academy Press: Washington, DC, USA, 1981. [Google Scholar]
  18. Smith, K.R.; Corvalán, C.F.; Kjellström, T. How much global ill health is attributable to environmental factors? Epidemiol. Camb. Mass 1999, 10, 573–584. [Google Scholar] [CrossRef] [Green Version]
  19. Haines, D.A.; Saravanabhavan, G.; Werry, K.; Khoury, C. An overview of human biomonitoring of environmental chemicals in the Canadian Health Measures Survey: 2007–2019. Int. J. Hyg. Environ. Health 2017, 220, 13–28. [Google Scholar] [CrossRef] [Green Version]
  20. Statistics Canada. Census Program. 2001. Available online: https://www12.statcan.gc.ca/census-recensement/index-eng.cfm?MM=1 (accessed on 1 May 2021).
  21. Hodgson, T.A.; Meiners, M.R. Cost-of-Illness Methodology: A Guide to Current Practices and Procedures. Milbank Mem. Fund Q. Health Soc. 1982, 60, 429. [Google Scholar] [CrossRef] [Green Version]
  22. Weinstein, M.C.; Siegel, J.E.; Gold, M.R.; Kamlet, M.S.; Russell, L.B. Recommendations of the Panel on Cost-effectiveness in Health and Medicine. JAMA 1996, 276, 1253–1258. [Google Scholar] [CrossRef]
  23. United States Department of Labor, Bureau of Labor Statistics. Consumer Price Index. Available online: http://www.bls.gov/cpi/ (accessed on 1 May 2021).
  24. OECD. OECD Data—Finance. Available online: https://data.oecd.org/searchresults/?hf=20&b=0&r=%2Bf%2Ftype%2Findicators&r=%2Bf%2Ftopics_en%2Ffinance&l=en&s=score (accessed on 1 May 2021).
  25. World Bank. World Bank Open Data. Available online: https://data.worldbank.org/?most_recent_year_desc=true (accessed on 1 May 2021).
  26. World Bank. GDP (Constant 2010 US$)—Canada. Available online: https://data.worldbank.org/indicator/NY.GDP.MKTP.KD?locations=CA (accessed on 1 May 2021).
  27. Chemicals Management Plan Science Committee. Committee Report: Advancing Consideration of Endocrine-Disrupting Chemicals under the Canadian Environmental Protection Act, 1999. 2018. Available online: https://www.canada.ca/en/health-canada/services/chemical-substances/chemicals-management-plan/science-committee/meeting-records-reports/committee-report-july-18-19-2018.html#a3 (accessed on 1 May 2021).
  28. Trasande, L.; Zoeller, R.T.; Hass, U.; Kortenkamp, A.; Grandjean, P.; Myers, J.P.; DiGangi, J.; Hunt, P.M.; Rüdel, R.; Sathyanarayana, S.; et al. Burden of disease and costs of exposure to endocrine disrupting chemicals in the European Union: An updated analysis. Andrology 2016, 4, 565–572. [Google Scholar] [CrossRef] [Green Version]
  29. Bopp, S.K.; Barouki, R.; Brack, W.; Costa, S.D.; Dorne, J.-L.C.; Drakvik, P.E.; Faust, M.; Karjalainen, T.K.; Kephalopoulos, S.; van Klaveren, J.; et al. Current EU research activities on combined exposure to multiple chemicals. Environ. Int. 2018, 120, 544–562. [Google Scholar] [CrossRef] [PubMed]
  30. Trasande, L.; Vandenberg, L.N.; Bourguignon, J.-P.; Myers, J.P.; Slama, R.; Saal, F.V.; Zoeller, R.T. Peer-reviewed and unbiased research, rather than ‘sound science’, should be used to evaluate endocrine-disrupting chemicals. J. Epidemiol. Community Health 2016, 70, 1051–1056. [Google Scholar] [CrossRef] [Green Version]
  31. Karthikeyan, B.S.; Ravichandran, J.; Mohanraj, K.; Vivek-Ananth, R.; Samal, A. A curated knowledgebase on endocrine disrupting chemicals and their biological systems-level perturbations. Sci. Total Environ. 2019, 692, 281–296. [Google Scholar] [CrossRef] [PubMed]
  32. Shaffer, R.M.; Sellers, S.P.; Baker, M.G.; Kalman, R.D.B.; Frostad, J.; Suter, M.; Anenberg, S.C.; Balbus, J.; Basu, N.; Bellinger, D.C.; et al. Improving and Expanding Estimates of the Global Burden of Disease Due to Environmental Health Risk Factors. Environ. Health Perspect. 2019, 127, 105001. [Google Scholar] [CrossRef] [Green Version]
  33. Damstra, T.; Barlow, S.; Bergman, A.; Kavlock, R.; Kraak, G. Global Assessment of the State-of-Science of Endocrine Disruptors; International Programme on Chemical Safety; World Health Organization: Geneva, Switzerland, 2002. [Google Scholar]
  34. Rissman, E.F.; Adli, M. Minireview: Transgenerational epigenetic inheritance: Focus on endocrine disrupting compounds. Endocrinology 2014, 155, 2770–2780. [Google Scholar] [CrossRef] [PubMed]
  35. Rochester, J.R.; Bolden, A.L. Bisphenol S and F: A Systematic Review and Comparison of the Hormonal Activity of Bisphenol A Substitutes. Environ. Health Perspect. 2015, 123, 643–650. [Google Scholar] [CrossRef]
  36. Parliament of Canada. Bill C-28. 2021. Available online: https://parl.ca/DocumentViewer/en/43-2/bill/C-28/first-reading (accessed on 1 May 2021).
  37. Chen, A.; Yolton, K.; Rauch, S.; Webster, G.; Hornung, R.; Sjödin, A.; Dietrich, K.; Lanphear, B. Prenatal Polybrominated Diphenyl Ether Exposures and Neurodevelopment in U.S. Children through 5 Years of Age: The HOME Study. Environ. Health Perspect 2014, 122, 856–862. [Google Scholar] [CrossRef] [Green Version]
  38. Elise, G. Childhood lead poisoning: Conservative estimates of the social and economic benefits of lead hazard control. Environ. Health Perspect. 2009, 117, 1162–1167. [Google Scholar] [CrossRef]
  39. Honeycutt, A.; Dunlap, L.; Chen, H.; Homsi, G.; Grosse, S.; Schendel, D. Economic Costs of Mental Retardation, Cerebral Palsy, Hearing Loss, and Vision Impairment—United States, 2003. Res. Soc. Sci. Disabil. 2004, 53, 57–59. [Google Scholar]
  40. Bellinger, D.; Croft, C. A strategy for comparing the contributions of environmental chemicals and other risk factors to neurodevelopment of children. Environ. Health Perspect. 2012, 120, 501–507. [Google Scholar] [CrossRef]
  41. Engel, S.; Wetmur, J.; Chen, J.; Zhu, C.; Barr, D.; Canfield, R.; Wolff, M. Prenatal exposure to organophosphates, paraoxonase 1, and cognitive development in childhood. Environ. Health Perspect. 2011, 119, 1182–1188. [Google Scholar] [CrossRef] [Green Version]
  42. Bouchard, M.; Chevrier, J.; Harley, K.; Kogut, K.; Vedar, M.; Calderon, N.; Trujillo, C.; Johnson, C.; Bradman, A.; Barr, D.; et al. Prenatal exposure to organophosphate pesticides and IQ in 7-year-old children. Environ. Health Perspect. 2011, 119, 1189–1195. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  43. Miodovnik, A.; Engel, S.; Zhu, C.; Ye, X.; Soorya, L.; Silva, M.; Calafat, A.; Wolff, M. Endocrine disruptors and childhood social impairment. Neurotoxicology 2011, 32, 261–267. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  44. Ofner, M.; Coles, A.; Decou, M.L. Autism Spectrum Disorder among Children and Youth in Canada 2018: A Report of the National Autism Spectrum Disorder Surveillance System. 2018. Available online: https://www.deslibris.ca/ID/10096072 (accessed on 3 July 2020).
  45. Buescher, A.; Cidav, Z.; Knapp, M.; Mandell, D. Costs of autism spectrum disorders in the United Kingdom and the United States. JAMA Pediatr. 2014, 168, 721–728. [Google Scholar] [CrossRef]
  46. Levin, M. The occurrence of lung cancer in man. Acta Unio Int. Contra Cancrum 1953, 9, 531–541. [Google Scholar] [PubMed]
  47. Gascon, M.; Vrijheid, M.; Martínez, D.; Forns, J.; Grimalt, J.; Torrent, M.; Sunyer, J. Effects of pre and postnatal exposure to low levels of polybromodiphenyl ethers on neurodevelopment and thyroid hormone levels at 4 years of age. Environ. Int. 2011, 37, 605–611. [Google Scholar] [CrossRef] [PubMed]
  48. Vasiliadis, H.-M.; Diallo, F.B.; Rochette, L.; Smith, M.; Langille, D.; Lin, E.; Kisely, S.; Fombonne, E.; Thompson, A.H.; Renaud, J.; et al. Temporal Trends in the Prevalence and Incidence of Diagnosed ADHD in Children and Young Adults between 1999 and 2012 in Canada: A Data Linkage Study. Can. J. Psychiatry Rev. Can. Psychiatr. 2017, 62, 818–826. [Google Scholar] [CrossRef] [PubMed]
  49. Sikora, D.M.; Vora, P.; Coury, D.L.; Rosenberg, D. Attention-Deficit/Hyperactivity Disorder Symptoms, Adaptive Functioning, and Quality of Life in Children With Autism Spectrum Disorder. Pediatrics 2012, 130, S91–S97. [Google Scholar] [CrossRef] [Green Version]
  50. Pelham, W.E.; Foster, E.M.; Robb, J.A. The Economic Impact of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents. J. Pediatr. Psychol. 2007, 32, 711–727. [Google Scholar] [CrossRef]
  51. Wu, H.; Bertrand, K.A.; Choi, A.L.; Hu, F.B.; Laden, F.; Grandjean, P.; Sun, Q. Persistent organic pollutants and type 2 diabetes: A prospective analysis in the nurses’ health study and meta-analysis. Environ. Health Perspect. 2013, 121, 153–161. [Google Scholar] [CrossRef] [Green Version]
  52. Turyk, M.; Anderson, H.; Knobeloch, L.; Imm, P.; Persky, V. Organochlorine exposure and incidence of diabetes in a cohort of Great Lakes sport fish consumers. Environ. Health Perspect. 2009, 117, 1076–1082. [Google Scholar] [CrossRef] [Green Version]
  53. Public Health Agency of Canada. Diabetes in Canada: Facts and Figures from a Public Health Perspective; Public Health Agency of Canada: Ottawa, ON, USA, 2012; Available online: http://ra.ocls.ca/ra/login.aspx?inst=centennial&url=https://www.deslibris.ca/ID/232351 (accessed on 3 April 2020).
  54. Rosella, L.C.; Lebenbaum, M.; Fitzpatrick, T.; O’Reilly, D.; Wang, J.; Booth, G.L.; Stukel, T.A.; Wodchis, W.P. Impact of diabetes on healthcare costs in a population-based cohort: A cost analysis. Diabet. Med. 2016, 33, 395–403. [Google Scholar] [CrossRef]
  55. Statistics Canada. The Consumer Price Index. Available online: https://www150.statcan.gc.ca/n1/en/catalogue/62-001-X (accessed on 31 March 2020).
  56. Iszatt, N.; Stigum, H.; Verner, M.-A.; White, R.A.; Govarts, E.; Murinova, L.P.; Schoeters, G.; Trnovec, T.; Legler, J.; Pelé, F.; et al. Prenatal and Postnatal Exposure to Persistent Organic Pollutants and Infant Growth: A Pooled Analysis of Seven European Birth Cohorts. Environ. Health Perspect. 2015, 123, 730–736. [Google Scholar] [CrossRef] [PubMed]
  57. Monteiro, P.O.A.; Victora, C.G. Rapid growth in infancy and childhood and obesity in later life—A systematic review. Obes. Rev. Off. J. Int. Assoc. Study Obes. 2005, 6, 143–154. [Google Scholar] [CrossRef] [PubMed]
  58. Ong, K.K.; Loos, R.J.F. Rapid infancy weight gain and subsequent obesity: Systematic reviews and hopeful suggestions. Acta Paediatr. 2006, 95, 904–908. [Google Scholar] [CrossRef] [PubMed]
  59. Rao, D.P.; Kropac, E.; Do, M.T.; Roberts, K.C.; Jayaraman, G.C. Childhood overweight and obesity trends in Canada. Health Promot. Chronic Dis. Prev. Can. Res. Policy Pract. 2016, 36, 194–198. [Google Scholar] [CrossRef] [Green Version]
  60. Valvi, D.; Mendez, M.; Martinez, D.; Grimalt, J.O.; Torrent, M.; Sunyer, J.; Vrijheid, M. Prenatal concentrations of polychlorinated biphenyls, DDE, and DDT and overweight in children: A prospective birth cohort study. Environ. Health Perspect. 2012, 120, 451–457. [Google Scholar] [CrossRef] [Green Version]
  61. Finkelstein, E.A.; Graham, W.C.K.; Malhotra, R. Lifetime Direct Medical Costs of Childhood Obesity. Pediatrics 2014, 133, 854–862. [Google Scholar] [CrossRef] [Green Version]
  62. Trasande, L.; Liu, Y.; Fryer, G.; Weitzman, M. Effects of childhood obesity on hospital care and costs, 1999–2005. Health Aff. Proj. HOPE 2009, 28, 751–760. [Google Scholar] [CrossRef]
  63. Trasande, L.; Chatterjee, S. The impact of obesity on health service utilization and costs in childhood. Obesity 2009, 17, 1749–1754. [Google Scholar] [CrossRef]
  64. Trasande, L. How Much Should We Invest In Preventing Childhood Obesity? Health Aff. 2010, 29, 372–378. [Google Scholar] [CrossRef] [Green Version]
  65. Trasande, L.; Elbel, B. The economic burden placed on healthcare systems by childhood obesity. Expert Rev. Pharmacoecon. Outcomes Res. 2012, 12, 39–45. [Google Scholar] [CrossRef]
  66. Song, Y.; Hauser, R.; Hu, F.B.; Franke, A.A.; Liu, S.; Sun, Q. Urinary concentrations of bisphenol A and phthalate metabolites and weight change: A prospective investigation in US women. Int. J. Obes. 2014, 38, 1532–1537. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  67. Morin, S.; Tsang, J.F.; Leslie, W.D. Weight and body mass index predict bone mineral density and fractures in women aged 40 to 59 years. Osteoporos. Int. 2009, 20, 363–370. [Google Scholar] [CrossRef] [PubMed]
  68. Statistics Canada. Mean Height, Weight, Body Mass Index (BMI) and Prevalence of Obesity, by Collection Method and Sex, Household Population Aged 18 to 79, Canada, 2008, 2007 to 2009, and 2005. 2015. Available online: https://www150.statcan.gc.ca/n1/pub/82-003-x/2011003/article/11533/tbl/tbl1-eng.htm (accessed on 2 April 2020).
  69. Janssen, I.; Lam, M.; Katzmarzyk, P.T. Influence of overweight and obesity on physician costs in adolescents and adults in Ontario, Canada. Obes. Rev. Off. J. Int. Assoc. Study Obes. 2009, 10, 51–57. [Google Scholar] [CrossRef] [PubMed]
  70. Muennig, P.; Lubetkin, E.; Jia, H.; Franks, P. Gender and the Burden of Disease Attributable to Obesity. Am. J. Public Health 2006, 96, 1662–1668. [Google Scholar] [CrossRef] [PubMed]
  71. Sun, Q.; Cornelis, M.C.; Townsend, M.K.; Tobias, D.; Eliassen, A.H.; Franke, A.A.; Hauser, R.; Hu, F. B Association of Urinary Concentrations of Bisphenol A and Phthalate Metabolites with Risk of Type 2 Diabetes: A Prospective Investigation in the Nurses’ Health Study (NHS) and NHSII Cohorts. Environ. Health Perspect. 2014, 122, 616–623. [Google Scholar] [CrossRef] [PubMed]
  72. Valvi, D.; Casas, M.; Mendez, M.A.; Ballesteros-Gmez, A.; Luque, N.; Rubio, S.; Sunyer, J.; Vrijheid, M. Prenatal bisphenol a urine concentrations and early rapid growth and overweight risk in the offspring. Epidemiol. Camb. Mass. 2013, 24, 791–799. [Google Scholar] [CrossRef]
  73. Ma, S.; Frick, K.D. A simulation of affordability and effectiveness of childhood obesity interventions. Acad. Pediatr. 2011, 11, 342–350. [Google Scholar] [CrossRef]
  74. Vafeiadi, M.; Roumeliotaki, T.; Myridakis, A.; Chalkiadaki, G.; Fthenou, E.; Dermitzaki, E.; Karachaliou, M.; Sarri, K.; Vassilaki, M.; Stephanou, E.; et al. Association of early life exposure to bisphenol A with obesity and cardiometabolic traits in childhood. Environ. Res. 2016, 146, 379–387. [Google Scholar] [CrossRef]
  75. Kuhle, S.; Kirk, S.; Ohinmaa, A.; Yasui, Y.; Allen, A.C.; Veugelers, P.J. Use and cost of health services among overweight and obese Canadian children. Int. J. Pediatr. Obes. 2011, 6, 142–148. [Google Scholar] [CrossRef]
  76. Tarride, J.-E.; Haq, M.; Taylor, V.H.; Sharma, A.M.; Nakhai-Pour, H.R.; O’Reilly, D.; Xie, F.; Dolovich, L.; Goeree, R. Health status, hospitalizations, day procedures, and physician costs associated with body mass index (BMI) levels in Ontario, Canada. Clin. Outcomes Res. CEOR 2012, 4, 21–30. [Google Scholar] [CrossRef] [Green Version]
  77. Hardell, L.; Bavel, B.; Lindström, G.; Eriksson, M.; Carlberg, M. In utero exposure to persistent organic pollutants in relation to testicular cancer risk. Int. J. Androl. 2006, 29, 228–234. [Google Scholar] [CrossRef] [PubMed]
  78. Canadian Cancer Society. Canadian Cancer Society’s Steering Committee: Canadian Cancer Statistics 2010; Canadian Cancer Society: Toronto, ON, Canada, 2010. Available online: https://www.cancer.ca/~/media/cancer.ca/CW/cancer%20information/cancer%20101/Canadian%20cancer%20statistics/Canadian-Cancer-Statistics-2010-EN.pdf?la=en (accessed on 25 September 2020).
  79. de Oliveira, C. Phase-specific and lifetime costs of cancer care in Ontario, Canada. BMC Cancer 2016, 16, 809. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  80. Kiviranta, H.; Main, K.M.; Vartiainen, T.; Skakkebaek, N.E.; Virtanen, H.E.; Toppari, J.; Tuomisto, J.T.; Sundqvist, E.; Tuomisto, J. Flame retardants in placenta and breast milk and cryptorchidism in newborn boys. Environ. Health Perspect. 2007, 115, 1519–1526. [Google Scholar] [CrossRef]
  81. Mannetje, A. ’t; Coakley, J.; Mueller, J.F.; Harden, F.; Toms, L.-M.; Douwes, J. Partitioning of persistent organic pollutants (POPs) between human serum and breast milk: A literature review. Chemosphere 2012, 89, 911–918. [Google Scholar] [CrossRef]
  82. Hsieh, M.H.; Roth, D.R.; Meng, M.V. Economic analysis of infant vs. postpubertal orchiopexy to prevent testicular cancer. Urology 2009, 73, 776–781. [Google Scholar] [CrossRef]
  83. Meeker, J.D.; Ferguson, K.K. Urinary Phthalate Metabolites Are Associated With Decreased Serum Testosterone in Men, Women, and Children From NHANES 2011–2012. J. Clin. Endocrinol. Metab. 2014, 99, 4346–4352. [Google Scholar] [CrossRef] [Green Version]
  84. Araujo, A.B.; Dixon, J.M.; Suarez, E.A.; Murad, M.H.; Guey, L.T.; Wittert, G.A. Clinical review: Endogenous testosterone and mortality in men: A systematic review and meta-analysis. J. Clin. Endocrinol. Metab. 2011, 96, 3007–3019. [Google Scholar] [CrossRef]
  85. Statistics Canada. Trends in Mortality Rates, 2000 to 2013. 7 February 2017. Available online: https://www150.statcan.gc.ca/n1/pub/82-625-x/2017001/article/14775-eng.htm (accessed on 20 September 2020).
  86. Max, W. Present Value of Lifetime Earnings, 2009; Unpublished Tables; Institute for Aging, University of California: San Francisco, CA, USA, 2013. [Google Scholar]
  87. Buck Louis, G.M.; Sundaram, R.; Sweeney, A.M.; Schisterman, E.F.; Maisog, J.; Kannan, K. Urinary bisphenol A, phthalates, and couple fecundity: The Longitudinal Investigation of Fertility and the Environment (LIFE) Study. Fertil. Steril. 2014, 101, 1359–1366. [Google Scholar] [CrossRef] [Green Version]
  88. Gunby, J. Assisted Reproductive Technologies (ART) in Canada: 2010 Results from the Canadian ART Register; IVF Directors Group of the Canadian Fertility and Andrology Society: Montreal, QC, Canada; Available online: https://cfas.ca/_Library/_documents/CARTR_2010.pdf (accessed on 25 September 2020).
  89. Bushnik, T.; Cook, J.L.; Yuzpe, A.A.; Tough, S.; Collins, J. Estimating the prevalence of infertility in Canada. Hum. Reprod. 2012, 27, 738–746. [Google Scholar] [CrossRef] [Green Version]
  90. Zhang, J.; Yu, K.F. What’s the Relative Risk?A Method of Correcting the Odds Ratio in Cohort Studies of Common Outcomes. JAMA 1998, 280, 1690–1691. [Google Scholar] [CrossRef] [Green Version]
  91. United Nations Population Division. World Contraceptive Use. 2014. Available online: http://data.un.org/DocumentData.aspx?id=356 (accessed on 25 September 2020).
  92. Statistics Canada, Marital Status (13), Age (16) and Sex (3) for the Population 15 Years and Over of Canada, Provinces and Territories and Census Metropolitan Areas, 1996 to 2016 Censuses—100% Data. 2019. Available online: https://www12.statcan.gc.ca/census-recensement/2016/dp-pd/dt-td/Rp-eng.cfm?LANG=E&APATH=3&DETAIL=0&DIM=0&FL=A&FREE=0&GC=0&GID=0&GK=0&GRP=1&PID=109650&PRID=10&PTYPE=109445&S=0&SHOWALL=0&SUB=0&Temporal=2016&THEME=117&VID=0&VNAMEE=&VNAMEF= (accessed on 20 September 2020).
  93. Chambers, G.M.; Sullivan, E.A.; Ishihara, O.; Chapman, M.G.; Adamson, G.D. The economic impact of assisted reproductive technology: A review of selected developed countries. Fertil. Steril. 2009, 91, 2281–2294. [Google Scholar] [CrossRef] [PubMed]
  94. Trabert, B.; Chen, Z.; Kannan, K.; Peterson, C.M.; Pollack, A.Z.; Sun, L.; Buck Louis, G.M. Persistent organic pollutants (POPs) and fibroids: Results from the ENDO study. J. Expo. Sci. Environ. Epidemiol. 2015, 25, 278–285. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  95. Marshall, L.M.; Spiegelman, D.; Barbieri, R.L.; Goldman, M.B.; Manson, J.E.; Colditz, G.A.; Willett, W.C.; Hunter, D.J. Variation in the incidence of uterine leiomyoma among premenopausal women by age and race. Obstet. Gynecol. 1997, 90, 967–973. [Google Scholar] [CrossRef]
  96. Zimmermann, A.; Bernuit, D.; Gerlinger, C.; Schaefers, M.; Geppert, K. Prevalence, symptoms and management of uterine fibroids: An international internet-based survey of 21,746 women. BMC Womens Health 2012, 12, 6. [Google Scholar] [CrossRef] [Green Version]
  97. Soliman, A.M.; Yang, H.; Du, E.X.; Kelkar, S.S.; Winkel, C. The direct and indirect costs of uterine fibroid tumors: A systematic review of the literature between 2000 and 2013. Am. J. Obstet. Gynecol. 2015, 213, 141–160. [Google Scholar] [CrossRef] [PubMed]
  98. Al-Fozan, H.; Dufort, J.; Kaplow, M.; Valenti, D.; Tulandi, T. Cost analysis of myomectomy, hysterectomy, and uterine artery embolization. Am. J. Obstet. Gynecol. 2002, 187, 1401–1404. [Google Scholar] [CrossRef]
  99. Louis, G.M.B.; Peterson, C.M.; Chen, Z.; Croughan, M.; Sundaram, R.; Stanford, J.; Varner, M.W.; Kennedy, A.; Giudice, L.; Fujimoto, V.Y.; et al. Bisphenol A and phthalates and endometriosis: The Endometriosis: Natural History, Diagnosis and Outcomes Study. Fertil. Steril. 2013, 100, 162–169. [Google Scholar] [CrossRef] [Green Version]
  100. Missmer, S.A.; Hankinson, S.E.; Spiegelman, D.; Barbieri, R.L.; Marshall, L.M.; Hunter, D.J. Incidence of laparoscopically confirmed endometriosis by demographic, anthropometric, and lifestyle factors. Am. J. Epidemiol. 2004, 160, 784–796. [Google Scholar] [CrossRef]
  101. Levy, A.R.; Osenenko, K.M.; Lozano-Ortega, G.; Sambrook, R.; Jeddi, M.; Bélisle, S.; Reid, R.L. Economic burden of surgically confirmed endometriosis in Canada. J. Obstet. Gynaecol. Can. JOGC J. Obstet. Gynecol. Can. JOGC 2011, 33, 830–837. [Google Scholar] [CrossRef]
  102. Murray, C.J.L.; Vos, T.; Lozano, R.; AlMazroa, M.A.; Memish, Z.A. Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990-2010: A systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012, 380, 2197–2223. [Google Scholar] [CrossRef]
  103. Constantino, J.; Gruber, C. Social Responsiveness Scale (SRS); Western Psychological Services: Torrance, CA, USA, 2005. [Google Scholar]
Table
Table 1. Attributable burden of disease for 15 exposure–response relationships in Canada.
Table 1. Attributable burden of disease for 15 exposure–response relationships in Canada.
Exposure Response RelationshipTarget PopulationBase Case EstimateSensitivity Analyses
Neurodevelopmental deficits
PBDE and IQ points loss and intellectual disabilityAll neonates374,395 IQ points lost; 1610 ID cases790,865–925,481 IQ points lost; 3674–4491 ID cases
OP and IQ points loss and intellectual disabilityAll neonates152,922 IQ points lost; 377 ID cases 50,014–201,497 IQ points lost; 111–522 ID cases
Multiple exposures and ADHDChildren aged 12 years180 cases (OPs)329 cases (PBDE)
Phthalates and autismChildren aged 8 years118 cases in males, 28 cases in females 47–236 cases in boys, 11–56 cases in girls
Metabolic disorders
DDE and childhood obesityChildren aged 10 years114 cases 318 cases
DDE and adult diabetesAdults aged 40–59 years3270 cases 36,209 cases
DEHP and adult obesityWomen aged 40–59 years2093 casesNA
DEHP and adult diabetesWomen aged 40–59 years225 casesNA
BPA and childhood obesityChildren aged 4 years1023 cases711 cases
Male reproductive disorders
PBDE and testicular cancerMen aged 20–79 years316 cases96–423 cases
PBDE and cryptorchidismAll male neonates567 casesNA
Phthalates and male infertility resulting in increased assisted reproductive technologyMen aged 20–39 years1395 casesNA
Phthalates and low testosterone resulting in increased early mortalityMen aged 60–79 years3385 casesNA
Female reproductive disorders
DDE and fibroidsWomen aged 15–54 years2254 casesNA
DEHP and endometriosisWomen aged 20–39 years10,151 cases NA
PBDE = polybrominated diphenyl ethers, OP = organophosphate pesticides, DDE = dichlorodiphenyldichloroethylene, DEHP = di-2-ethylhexylphthalate, IQ = intellectual quotient, NA = alternative inputs not available for sensitivity analyses, ADHD = attention deficit hyperactivity disorder.
Table
Table 2. Cost estimates (2010 CAD) for disorders associated with exposure to EDCs in Canada.
Table 2. Cost estimates (2010 CAD) for disorders associated with exposure to EDCs in Canada.
Exposure Response RelationshipBase Case EstimateSensitivity Analysis: Low-End EstimateSensitivity Analysis: High-End Estimate or Alternative Scenario
Neurodevelopmental deficits
PBDE and IQ points loss and intellectual disability$8.8 billion (IQ); $2.6 billion (ID)NA$21.8 billion (IQ); $7.4 billion (ID)
OP and IQ points loss and intellectual disability$3.6 billion (IQ); $619 million (ID)$1.2 billion (IQ); $182 million (ID)$4.7 billion (IQ); $858 million (ID)
Multiple exposures and ADHD$34.8 million$28.4 million$75.4 million
Multiple exposures and autism$188.2 million for boys, $44.7 million for girls $75.3 million for boys, $17.9 million for girls $376.5 million for boys, $89.5 million for girls
Metabolic disorders
DDE and childhood obesity$2.5 millionNA$6.9 million
DDE and adult diabetes$385.2 millionNA$4.3 billion
DEHP and adult obesity$684.8 millionNANA
DEHP and adult diabetes$25.8 millionNANA
BPA and childhood obesity$59 million$41 millionNA
Male reproductive disorders
PBDE and testicular cancer$7.3 million $2.2 million$9.8 million
PBDE and cryptorchidism$5.8 millionNANA
Phthalates and male infertility resulting in increased assisted reproductive technology$17.0 millionNANA
Phthalates and low testosterone resulting in increased early mortality$1.8 billionNANA
Female reproductive disorders
DDE and fibroids$4.2 millionNANA
DEHP and endometriosis$5.7 billion NANA
Total$24.6 billionNANA
All cost estimates are reported in the 2010 Canadian dollar.
Table
Table 3. Comparison of attributable disease burden and economic costs (base case estimates, 2010 USD) in the US, EU and Canada with 2010 population estimates.
Table 3. Comparison of attributable disease burden and economic costs (base case estimates, 2010 USD) in the US, EU and Canada with 2010 population estimates.
USAEUCanada
Exposure-Response RelationshipDisease BurdenEconomic Costs (USD)Disease BurdenEconomic Costs (USD)Disease BurdenEconomic Costs (USD)
Neurodevelopmental deficits
PBDE and IQ points loss and intellectual disability11 million IQ points lost; 43,000 ID cases$266 billion873,000 IQ points lost; 3290 ID cases$12.6 billion374,000 IQ points lost; 1610 ID cases $7.2 billion (IQ); $2.2 billion (ID)
OP and IQ points loss and intellectual disability1.8 million IQ points lost; 7500 ID cases$44.7 billion13 million IQ points lost; 59,300 ID cases$194.0 billion153,000 IQ points lost; 377 ID cases $3.0 billion (IQ); $507 million (ID)
Multiple exposures and ADHD4400 cases$698.0 million19,400–31,200 cases$2.3 billion180 cases$28.5 million
Multiple exposures and autism787 cases in boys, 754 cases in girls$1.0 billion in boys, $984.0 million in girls 316 cases$265.1 million118 cases in boys, 28 cases in girls $154.2 million for boys, $36.6 million for girls
Metabolic disorders
DDE and childhood obesity857 cases$29.6 million1555 cases$32.7 million114 cases $2.1 million
DDE and adult diabetes24,900 cases$1.8 billion28,200 cases$1.1 billion3270 cases $315.4 million
DEHP and adult obesity5900 cases$1.7 billion53,900 cases$20.8 billion2093 cases$560.9 million
DEHP and adult diabetes1300 cases$91.4 million20,500 cases$807.2 million225 cases$21.2 million
BPA and childhood obesity33,000 cases$2.4 billion42,400 cases$2.0 billion1023 cases$48.3 million
Male reproductive disorders
PBDE and testicular cancer3600 cases$81.5 million6830 cases$1.1 billion316 cases$6.0 million
PBDE and cryptorchidism4300 cases$35.7 million4615 cases$172.6 million567 cases$ 4.8 million
Phthalates and male infertility resulting in increased assisted reproductive technology240,100 cases$2.5 billion618,000 cases$6.3 billion1395 cases$13.9 million
Phthalates and low testosterone resulting in increased early mortality10,700 attributable deaths$8.8 billion24,800 attributable deaths $10.6 billion3385 attributable deaths $1.5 billion
Female reproductive disorders
DDE and fibroids37,000 cases$259.0 million56,700 cases$216.8 million2254 cases$3.5 million
DEHP and endometriosis86,000 cases$47.0 billion145,000 cases$1.7 billion 10,151 cases $4.6 billion
Exchange rate €1 = $1.33 USD; $1 USD = $1.221 CAD via PPP. Data for population estimates obtained from World Bank [25].
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Share and Cite

MDPI and ACS Style

Malits, J.; Naidu, M.; Trasande, L. Exposure to Endocrine Disrupting Chemicals in Canada: Population-Based Estimates of Disease Burden and Economic Costs. Toxics 2022, 10, 146. https://doi.org/10.3390/toxics10030146

AMA Style

Malits J, Naidu M, Trasande L. Exposure to Endocrine Disrupting Chemicals in Canada: Population-Based Estimates of Disease Burden and Economic Costs. Toxics. 2022; 10(3):146. https://doi.org/10.3390/toxics10030146

Chicago/Turabian Style

Malits, Julia, Mrudula Naidu, and Leonardo Trasande. 2022. "Exposure to Endocrine Disrupting Chemicals in Canada: Population-Based Estimates of Disease Burden and Economic Costs" Toxics 10, no. 3: 146. https://doi.org/10.3390/toxics10030146

APA Style

Malits, J., Naidu, M., & Trasande, L. (2022). Exposure to Endocrine Disrupting Chemicals in Canada: Population-Based Estimates of Disease Burden and Economic Costs. Toxics, 10(3), 146. https://doi.org/10.3390/toxics10030146

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop