The Cost of Inaction

Costs related to human health and endocrine disrupting chemicals

Ing-Marie Olsson Ressner

Swedish Chemicals Agency

ing-marie.olsson@kemi.se

Publications

• ”The Cost of Inaction - A socioeconomic analysis of costs linked to effects of endocrine disrupting substances on male reproductive health” Report available at homepage of Nordic Council of Ministers : http://dx.doi.org/10.6027/TN2014-557

• ”Estimating Burden and Disease Costs of Exposure to Endcorine-Disrupting Chemicals in the European Union” Trasande et al. J Clin Endocrinol Metab 2015*

*) One of four publications based on an structured collaboration between scientists working according to the Intergovernmental Panel on Climate Change weight-of-evidence characterization for propbalility of causation. • Trasande et al 2015 – method description• Bellanger at el 2015 – neurobehavioral deficits and disease• Legler et al 2015 – metabolic disease• Hauser et al. 2015 – male reproductive disordersPublicerade i J Clin Endcrinol Metab http://www.endocrine.org/news-room/current-press-releases/estimated-costs-of-endocrine-disrupting-chemical-exposure-exceed-150-billion-annually-in-eu

Background and purpose

• Developing criteria for EDCs in the EU

• Impact assessment ongoing

• Potential benefits to society related to human health

• Contribution to the impact assessment

Nordic methodology - model

Endocrine distruptors

Intangible costs (Suffering and premature death)

Direct costs

Testicular cancer

  

Cost of treatment

Effect

Antiandrogens 

Oestrogens

Infertility due to low semen

quality

Hypospadias

Cryptorchidism

Indirect costs

 Cost of

production losses due

to disability or contact

with health care

Methodology cont’d

• Assumptions and uncertainties– Incidences and costs– Discounting (4%) – due to latency of effect– Assuming a causal link– Etiological fractions used:

• 2%, 20%, 40%• Communication with experts• Knowledge about genetic fractions (approx. 25%)

included• Variability, other ‘env. factors’ (diet, obesity,

smoking, alcohol)

Results the Nordic reportCost of effects on human male reproduction in EU28 due to endocrine disruptors at different levels of assumed etiological fractions (millions of Euro per year of exposure)

*The intangible costs of infertility are not quantified in this report

Results the Nordic report

Estimated costs of effects on human male reproduction in EU28 due to endocrine disruptors at different levels of assumed etiological fractions (millions of Euro per year of exposure)

Etiological fraction

Testicular cancer

Infertility Hypospadias Cryptorchidism Total

2% 25 7 9 18 59

20% 249 72 89 181 592

40% 499 145 178 363 1184

The Expert Panels

• Focus on non-banned chemicals – PBDE– organophosphate pesticides – DDE – BPA– phthalates

• Endpoints studied– Obesity/diabetes– Male reproductive health– Neurodevelopmental disability– Breast cancer– Female reproductive conditions

Method - Expert panel

• Epidemiological evidence• Toxicological evidence

Trasande et al JCEM 2015;adapted from http://www.ipcc.ch/meetings/ar4-workshops-express-meetings/uncertainty-guidance-note.pdf

Adapting IPCC criteria to integrate epidemiologic and toxicologic evidence

Method - Expert panel cont’d

• Biomonitoring/exposure data

• Attributable disease burden = Disease rate x Attributable fraction (AF) x Population size

• Attributable Costs = Disease rate x AF x Population size x Cost per case

Example PBDE – attributable cryptorchidism in Europe, 2010

Table 1. PBDE-Attributable Cryptorchidism in Europe, 2010        

Expert panel evaluation of epidemiological evidence Low

Expert panel evaluation of toxicological evidence Strong

Probability of causation, % 40-69

Percentile of exposure 0-9 10-24 25-49 50-74 75-89 >90

Percentile assumed 0 10 25 50 75 90

Estimated breast milk PBDE-47 (base case) <LOD <LOD <LOD 3.25 5.76 7.83

Estimated breast milk PBDE (lower bound) <LOD <LOD <LOD 1.78 2.98 4.07

Estimated breast milk PBDE-47 (higher bound) <LOD <LOD <LOD 6.02 10.66 14.51

Odds of cryptorchidism (base case) 1.00 1.00 1.00 1.00 1.53 1.93

Odds of cryptorchidism ( lower bound) 1.00 1.00 1.00 1.00 1.47 1.86

Attributable increment in cryptorchidism 4615 (4155-4615)

Attributable costs of cryptorchidism €130 million (€117-130 million)        

Abbreviation: LOD, Limit of detection

From: Male Reproductive Disorders, Diseases, and Costs of Exposure to Endocrine-Disrupting Chemiclas in the European UnionHauser et al. JCEM 2015

Overall Evaluations

Exposure OutcomeStrength of Human Evidence

Strength of ToxicologicEvidence

Probability of Causation

Polybrominated diphenyl ethers (PBDE)

IQ Loss and Intellectual Disability Moderate-to-high Strong 70-100%

Organophosphate pesticidesIQ Loss and Intellectual Disability Moderate-to-high Strong 70-100%

Dichlorodiphenytrichloroethane (DDE) Childhood obesity Moderate Moderate 40-69%Dichlorodiphenytrichloroethane (DDE) Adult diabetes Low Moderate 20-39%Di-2-ethylhexylphthalate (DEHP) Adult obesity Low Strong 40-69%Di-2-ethylhexylphthalate (DEHP) Adult diabetes Low Strong 40-69%Bisphenol A Childhood obesity Very low-to-low Strong 20-69%Polybrominateddiphenyl ethers (PBDE) Testicular cancer Very low-to-low Weak 0-19%Polybrominateddiphenyl ethers (PBDE) Cryptorchidism Low Strong 40-69%

Benzyl and butylphthalates

Male Infertility, Resulting in Increased Assisted Reproductive Technology Low Strong 40-69%

Phthalates Low testosterone, Resulting in Increased Early Mortality Low Strong 40-69%

Multiple exposures ADHD Low-to-moderate Strong 20-69%Multiple exposures Autism Low Moderate 20-39%

Trasande et al J Clin Endo Metab epub Mar 5 2015

Uncertainty and probability of causation - Monte Carlo Analysis

Trasande et al J Clin Endo Metab epub Mar 5 2015

http://www.kemikalieinspektionen.se/

Studies on costs

HEAL 2014• Total EU cost for

diseases related to EDC

• Etiological fraction (EF)2-5 %

• Direct costs only• No discounting• 13-31 billion/yr

– of these 0.5-0.7% related to human infertility, cryptorchidism and hypospadias. Testicular cancer not included

– With 2% EF 66-87 million/yr

Expert panel Hauser et al 2015

• Median estimate 157 billion/yr

• Epidemiological studies– PBDE –

cryptorchidism– Phthalate –

infertility– PBDE – testicular

cancer

• EU costs 5.7 billion/yr– Cryptorchidism 117-

130 million– Infertility

4.7 billion – Testicular cancer

313-848

Nordic 2014• Male reproductive

disorders– Cryptorchidism– Hypspadias– Testicular cancer– Infertility

• Etiological fraction (EF) 2, 20 or 40 %

• 59, 592 or 1184 million/yr– Cryptorchidism

18-363 million– Infertility 7-145

million– Testicular cancer

25-499 million

Conclusions and Perspectives

• Contribution to the EU impact assessment - substantial economic savings can likely be achieved by limiting exposure

• Growing demand to assess economic aspects • Present studies

– Underestimates – conservative apporaches– Environmental costs not included– Different approaches– Latency of effects

• Important to develop methodology– Extensive patient registers or human cases a prerequisite for

chemicals regulation? – How much do we need to know?

• In order to prevent – there is a need to base estimates on (eco)toxicity studies, in vitro, in silico and data modelling

Acknowledgement

Nordic colleagues• Marie Louise Holmer, Danish Environmental

Protection Agency• Ing-Marie Olsson, Swedish Chemicals Agency• Mattias Carlsson, Swedish Chemicals Agency• Christine Bjørge, Norwegian Environment Agency• Kenneth Birkeli, Norwegian Environment Agency• Helena Niëmela, Finnish Safety and Chemicals

Agency• Juha Lakso, Finnish Safety and Chemicals Agency

Consultant for the health economic part

Supported by Nordic Council of Ministers

Estimating burden and disease costs of exposure to EDCs in EU• Associate Professor Leonardo Trasande,

New York University (NYU) School of Medicine

• Steering committee: R. Thomas Zoeller, Andreas Kortenkamp, Philippe Grandjean, John Peterson Myers, Joe DiGangi, Martine Bellanger, Jerry Heindel

• Expert panel slead: Russ Hauser, Ana Soto, Paul A. Fowler, Patricia Hunt, Juliette Legler, Ruthann Rudel, Niels Skakkebaek

• Other participants: Barbara Cohn, Frederic Bois, Sheela Sathyanarayana, Jorma Toppari, Anders Juul, Ulla Hass, Bruce Blumberg, Miquel Porta, Eva Govarts, Barbara Demeneix

• Technical and logistical support: Charles Persoz, Robert Barouki, and Marion Le Gal of the French National Alliance for Life Sciences and Health and Lindsey Marshall, Bilal Mughal, and Bolaji Seffou of UMR7221 Paris

Funding• John Merck Fund, Broad Reach, Oak

Foundation

Thank you for your attention!