Endocrine disruptors in the healthcare sector
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Transcript of Endocrine disruptors in the healthcare sector
Health Care Without Harm Europe
Endocrine Disruptors in the Health Care Sector
Wednesday 24th September 15:30-16:30 CEST
What are EDCs&
How does exposure affect human health?
R. Thomas ZoellerBiology Department
College of Natural Sciences
What is an Endocrine Disrupting Chemical?
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”
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
Example:PCBs, Brain Development and Thyroid
Hormone Action
Schantz SL, Widholm JJ, Rice DC. Environ Health Perspect. 2003 Mar;111(3):357-576.
PCB exposure is associated
with cognitive deficits
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?
PCB exposure in animals almost uniformly causes
a reduction in serum total and free (not shown) T4.
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.
2530354045505560
RC3 mRNA in DentateGyrus (Density)
* *
RC3
Pseudocolor image of Autoradiogram following in situ
hybridization for RC3 mRNA
Cx
DG
0 mg/kg1 mg/kg4 mg/kg8 mg/kgA1254 Dose
PCB effects on serum T4 were not consistent with PCB effect on TH-regulated genes
PCBs in in vitro and in vivo studies
Non-ortho PCB congenerCoplanarDioxin-like
Mono-ortho PCB congenerNon-coplanar
Di-ortho PCB congenerNon-coplanar
Gauger, KJ. et al, (2007); Envir. Health Pers. 115(11), 1623-1630
Are there TR agonists among PCB congeners?
PCBs in in vitro and in vivo studiesGauger, KJ. et al, (2007); Envir. Health Pers. 115(11), 1623-1630
Only the right mixture activated the TR
4. Hypothesis
PCBs in in vitro and in vivo studies
CYP1A1
OHOH
TH target genes
TRTR
TRE
AHRXRE
ARNTCYP1A1
coplanarPCB 126
non-coplanar
PCB 105PCB 138
PCB 153PCB 118
Testing the hypothesis in humansIf 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?
CYP1A1 is Strongly Correlated
CYP1A1 not Correlated with T4
PL&GH-V in CYP±
ConclusionsAnimal 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.
• 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?
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.
Health Care Without Harm Europe
Endocrine Disruptors in the Health Care Sector
Wednesday 24th September 15:30-16:30 CEST
Children are a product of theirenvironment
Gavin W. ten Tusscher, M.D., Ph.D., paediatricianDepartment of Paediatrics and Neonatology
Westfriesgasthuis, Hoorn, Netherlands
Webinar, 24/09/2014
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Overview
– What’s the problem?
– What’s the danger?
– What’s the solution?
Webinar, 24/09/2014
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Health care: a source, but not the primary source, of exposure to toxics
Fetus inWomb /Child atHome
Infant/Childin Hospital
Child atHome
Toxic Chemicals
Webinar, 24/09/2014
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Sources of exposure to toxic chemicals in hospitals
Mother-- Breastfeeding
Patient —Infant/Child
Medical Devices-- IV administration-- Enteral nutrition-- Direct contact
-- Inhalation-- Dermal
HospitalEnvironment
-- Inhalation(air quality)
-- Water-- Food
-- Dermal
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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
Webinar, 24/09/2014
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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
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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
Webinar, 24/09/2014
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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
Webinar, 24/09/2014
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Cohort
Webinar, 24/09/2014
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Results
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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
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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
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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
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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
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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
Webinar, 24/09/2014
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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
Webinar, 24/09/2014
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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)
Webinar, 24/09/2014
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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
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PrecautionaryPrinciple
– Safer alternatives for almost all products
– We need to actively choose better alternatives
– Choose PVC-free/DEHP-free
– “When in doubt, throw it out”
Webinar, 24/09/2014
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DatabaseGlucose 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
Not easy …
London, 18/11/2011
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Not easy …
London, 18/11/2011
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London, 18/11/2011
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London, 18/11/2011
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London, 18/11/2011
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London, 18/11/2011
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London, 18/11/2011
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London, 18/11/2011
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London, 18/11/2011
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London, 18/11/2011
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London, 18/11/2011
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London, 18/11/2011
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London, 18/11/2011
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Webinar, 24/09/2014
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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
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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!
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
Health Care Without Harm Europe
Endocrine Disruptors in the Health Care Sector
Q&A