Endocrine disruptors in the healthcare sector
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The document discusses the impact of endocrine disrupting chemicals (EDCs) on human health, particularly in healthcare settings, highlighting the risks associated with exposure to substances like PCBs and DEHP. It emphasizes that EDCs can interfere with hormone action and cognitive development, especially in vulnerable populations such as infants and children. The presentation calls for safer medical alternatives to reduce exposure to harmful chemicals present in medical devices and healthcare environments.
Endocrine disruptors in the healthcare sector
- 1. Health Care Without Harm Europe Endocrine Disruptors in the Health Care Sector Wednesday 24th September 15:30-16:30 CEST
- 2. What are EDCs & How does exposure affect human health? R. Thomas Zoeller Biology Department College of Natural Sciences
- 3. What is an Endocrine Disrupting Chemical?
- 4. What is an Endocrine Disrupting Chemical? “An ED is an exogenous chemical or mixture of chemicals that can interfere with any aspect of hormone action” – Endocrine Society “interfere” means to trigger or block hormone action “any aspect” means to interfere with the hormone receptor or with the delivery of the hormone to the receptor “hormone action” means “what the hormone does”
- 5. What is an Endocrine Disrupting Chemical? To test if a chemical interferes with hormone action, you have to know what the hormone does. The problem is that hormones do different things in different “places” at different times! So EDCs may interfere with a hormone’s action selectively…. Could be receptor isoform specific Could be “metabolism” specific Almost certain is differentially sensitive
- 6. Example: PCBs, Brain Development and Thyroid Hormone Action
- 7. Schantz SL, Widholm JJ, Rice DC. Environ Health Perspect. 2003 Mar;111(3):357-576. PCB exposure is associated with cognitive deficits
- 8. Thyroid hormone deficiency produces effects on cognitive function that are similar to that of PCB exposure Therefore, could PCB exposure be producing neurocognitive deficits by reducing thyroid hormone levels?
- 10. PCB exposure in animals almost uniformly causes a reduction in serum total and free (not shown) T4.
- 11. If PCB – induced reduction in serum T4 is predictive of “downstream” effects, then PCB exposure should reduce the expression of thyroid hormone responsive genes in the developing brain.
- 12. 25 30 35 40 45 50 55 60 RC3 mRNA in Dentate Gyrus (Density) * * RC3 Pseudocolor image of Autoradiogram following in situ hybridization for RC3 mRNA Cx DG 0 mg/kg 1 mg/kg 4 mg/kg 8 mg/kg A1254 Dose PCB effects on serum T4 were not consistent with PCB effect on TH- regulated genes
- 13. PCBs in in vitro and in vivo studies Non-ortho PCB congener Coplanar Dioxin-like Mono-ortho PCB congener Non-coplanar Di-ortho PCB congener Non-coplanar Gauger, KJ. et al, (2007); Envir. Health Pers. 115(11), 1623-1630 Are there TR agonists among PCB congeners?
- 14. PCBs in in vitro and in vivo studies Gauger, KJ. et al, (2007); Envir. Health Pers. 115(11), 1623-1630 Only the right mixture activated the TR
- 15. 4. Hypothesis PCBs in in vitro and in vivo studies CYP1A1 TH target genes TRTR TRE AHR XRE ARNT CYP1A1 coplanar PCB 126 non-coplanar PCB 105 PCB 138 PCB 153 PCB 118
- 16. Testing the hypothesis in humans If environmental chemicals (e.g., PCBs) can be “activated” by CYP1A1 to form TR agonists which then drive (±) TH-response genes independent of serum TH, then: CYP1A1 expression should be correlated with the expression of TH response genes?
- 17. CYP1A1 is Strongly Correlated
- 18. CYP1A1 not Correlated with T4
- 19. PL&GH-V in CYP±
- 20. Conclusions Animal studies demonstrate that some EDCs can interfere with thyroid hormone action in tissues (e.g., developing brain) in a manner that is not reflected in serum thyroid hormone levels. Human studies identify associations between toxicant exposures and measures of cognitive function (as well as other outcomes), but relationships with measures of thyroid function have been inconsistent. Capturing indices of hormone action in tissues will be essential to translate experimental studies to the human population.
- 21. • Ingestion: food, dust, water • Inhalation: gases, air particles • Dermal absorption: personal care, dust • Breast Milk “We live in a chemical soup” Is there summation or synergy?
- 22. Most Vulnerable Time for Exposure All of the chemicals highlighted before are found in cord blood at birth. But, each baby has a total of about 100 chemicals “on board”. One study. 10 cord samples. 287 commercial chemicals, pesticides, and pollutants.
- 23. Health Care Without Harm Europe Endocrine Disruptors in the Health Care Sector Wednesday 24th September 15:30-16:30 CEST
- 24. Children are a product of their environment Gavin W. ten Tusscher, M.D., Ph.D., paediatrician Department of Paediatrics and Neonatology Westfriesgasthuis, Hoorn, Netherlands
- 25. Webinar, 24/09/2014 Gavin ten Tusscher 25 Overview – What’s the problem? – What’s the danger? – What’s the solution?
- 26. Webinar, 24/09/2014 Gavin ten Tusscher 26 Health care: a source, but not the primary source, of exposure to toxics Fetus in Womb / Child at Home Infant/Child in Hospital Child at Home Toxic Chemicals
- 27. Webinar, 24/09/2014 Gavin ten Tusscher 27 Sources of exposure to toxic chemicals in hospitals Mother -- Breast feeding Patient — Infant/Child Medical Devices -- IV administration -- Enteral nutrition -- Direct contact -- Inhalation -- Dermal Hospital Environment -- Inhalation (air quality) -- Water -- Food -- Dermal
- 28. Webinar, 24/09/2014 Gavin ten Tusscher 28 Most at risk – Foetus, prematurely born, small for gestational age, seriously ill child – Higher fat : water ratio but often less total body fat, long periods of exposure (in hospital) – Often life-long accumulative exposure – Organs (brain) still developing – Less effective blood-brain and blood-testis barrier
- 29. Webinar, 24/09/2014 Gavin ten Tusscher 29 DEHP – Softeners in plastic (PVC) – Known for 30 years that it leaks out of medical devices – Shown to leak from: • nasogastric tubes, respiratory tubes, endotracheal tubes, umbilical catheters, PVC blood bags, transfusion tubing systems, haemodialysis systems, cardiopulmonary bypass, continuous peritoneal dialysis, ECMO, infusion tubing – Suspected of teratogenicity and endocrine disruption
- 30. Webinar, 24/09/2014 Gavin ten Tusscher 30 DEHP and children – highly lipophilic (over placenta, in breast milk) – pancreatic lipase most important detoxifier – much lower levels of pancreatic lipase in neonates – greater absorption in children – vulnerable developmental windows
- 31. Webinar, 24/09/2014 Gavin ten Tusscher 31 NICU exposure to DEHP – 6 premature infants expected to have i.v. infusion for > 2 weeks included – 7 urine samples per infant – DEHP metabolites (mEHHP, mEOHP, mEHP) measured by CDC – 41 samples (1 sample no urine extractable) – 33 samples positive for all 3 metabolites Calafat et al. Pediatrics 2004;113(5):e429-3
- 32. Webinar, 24/09/2014 Gavin ten Tusscher 32 Cohort
- 33. Webinar, 24/09/2014 Gavin ten Tusscher 33 Results
- 34. Webinar, 24/09/2014 Gavin ten Tusscher 34 Discussion – geometric mean mEHP (100 ng/mL) prems • significantly higher than 19 toddlers 12 – 18 months (4.6 ng/mL) • 26 fold higher than US median for children 6 – 11 yrs – mEHHP and mEOHP 1-2 order of magnitude higher than US population (62 adults and children) – no correlation with specific procedure, GA, birth weight
- 35. Webinar, 24/09/2014 Gavin ten Tusscher 35 In utero exposure vs gestational age – Cord blood samples obtained in 84 consecutive newborns (82 singletons, 2 twins) – General practice hospital – 39 males, 45 females – 11 preterm, 3 VSGA, 4 SGA – No in vitro fertilisation – Sampling with glass devices Latini et al. Environ Health Perspect 2003;111(14):1783-5
- 36. Webinar, 24/09/2014 Gavin ten Tusscher 36 Results – Logistic regression: • Significant inverse relation mEHP & GA at birth (38.16 ± 2.34 vs 39.35 ± 1.35 wks) • OR 1.5 (CI 1.013-2.21) presence/absence mEHP
- 37. Webinar, 24/09/2014 Gavin ten Tusscher 37 Exposure – Endotracheal tubes show 6 – 12 % loss of DEHP during use most probably into the lungs Latini & Avery. Acta Paediatr 1999;88(10):1174-75 – Priming of ECMO circuits with saline increased circuit degradation Karle et al. Crit Care Med 1997;25(4):696-703 – DEHP negative infants showed 6.1 to 21.6 mcg/mL after a single exchange transfusion – DEHP found in lung tissue in preterms after mechanical ventilation Roth et al. Eur J Pediatr 1988;147(1):42-6
- 38. Webinar, 24/09/2014 Gavin ten Tusscher 38 DEHP – “normal” daily exposure 3-30 mcg/kg BW/day – NICU enteral nutrition 40-140 mcg/kg BW/day – NICU parental nutrition up to 2500 mcg/kg BW/day !! – Total daily intake in all children (< 19 yrs) > adults
- 39. Webinar, 24/09/2014 Gavin ten Tusscher 39 Bear in mind – DEHP toxicity shown in animal studies (long term toxicity & tissue deposition) – DEHP exposure is life-long, ubiquitous environmental contaminant – No longer in toys for children < 3 yrs (EU 1999/815/EG) – US FDA consider NICU patients at particular risk
- 40. Webinar, 24/09/2014 Gavin ten Tusscher 40 American Medical Association H-135.945 Encouraging Alternatives to PVC/DEHP Products in Healthcare AMA: (1) encourages hospitals and physicians to reduce and phase out polyvinyl chloride (PVC) medical device products, especially those containing Di(2- ethylhexyl)phthalate (DEHP), and urge adoption of safe, cost-effective, alternative products where available; and (2) urges expanded manufacturer development of safe, cost-effective alternative products to PVC medical device products, especially those containing DEHP. (BOT Action in response to referred for decision Res. 502, A-06)
- 41. Webinar, 24/09/2014 Gavin ten Tusscher 41 Summarising – Clear indications of DEHP exposure from medical devices – Animal studies show negative health effects – Exposure scenario in plastic laden environment – Increased exposure in infants
- 42. Webinar, 24/09/2014 Gavin ten Tusscher 42 Precautionary Principle – Safer alternatives for almost all products – We need to actively choose better alternatives – Choose PVC-free/DEHP-free – “When in doubt, throw it out”
- 43. Webinar, 24/09/2014 Gavin ten Tusscher 43 Database Glucose 3.75%-NaCl 0.225% IV bags PVC-Free Voluven IV bags PVC-Free NaCl 0.9% IV bags PVC-Free Glucose 20% IV bags Non-PVC Metronidazol 5mg/ml IV bags Non-PVC Gelofusine IV bags Ecobag® PVC-vrij Air Inlet Needle With Valve PVC-Free Infuus Medi-Cath 24G Intravenous Cannula BD Neoflon 24G Intravenous Cannula BD Vasculon 22G Intravenous Cannula Bioflow 24G Intravenous Cannula Microflex Infusion Set 27G
- 44. Not easy … London, 18/11/2011 Gavin ten Tusscher 44
- 45. Not easy … London, 18/11/2011 Gavin ten Tusscher 45
- 58. Webinar, 24/09/2014 Gavin ten Tusscher 58 Concluding – Our children are already being exposed to chemicals in concentrations that are too high – It is not wise to risk the health and development of our children
- 59. Webinar, 24/09/2014 Gavin ten Tusscher 59 Take home message – Let us learn from our mistakes and implement these lessons with other chemicals, especially when treating our patients – First do no harm !!! – Thank you for your attention!
- 60. To find PVC/phthalate-free alternatives: safermedicaldevices.org For more on EDCs: noharm-europe.org EDCs Free campaign page: edc-free-europe.org Global Green and Healthy Hospitals: greenhospitals.net
- 61. Health Care Without Harm Europe Endocrine Disruptors in the Health Care Sector Q&A