Download Webinar on EDCs in Health Care

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 Zoeller
Biology 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
PCB exposure
is associated
with cognitive
deficits
Schantz SL, Widholm
JJ, Rice DC. Environ
Health Perspect. 2003
Mar;111(3):357-576.
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.
PCB effects on serum T4 were not
consistent with PCB effect on THregulated genes
Cx
60
55
50
DG
RC3
RC3 mRNA in Dentate
Gyrus (Density)
*
*
45
40
35
30
25
Pseudocolor image of
Autoradiogram following in situ
hybridization for RC3 mRNA
0 mg/kg 1 mg/kg 4 mg/kg 8 mg/kg
A1254 Dose
Are there TR agonists among PCB
congeners?
Non-ortho PCB congener
Coplanar
Dioxin-like
Mono-ortho PCB congener
Non-coplanar
Di-ortho PCB congener
Non-coplanar
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
PCBs in in vitro and in vivo studies
Gauger, KJ. et al, (2007); Envir. Health Pers. 115(11), 1623-1630
4. Hypothesis
PCB 126
coplanar
AHR ARNT
XRE
CYP1A1
CYP1A1
TR TR
PCB 105
PCB 118
TRE
TH target genes
PCB 138
PCB 153
non-coplanar
PCBs in in vitro and in vivo studies
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?
CYP1A1 is Strongly Correlated
CYP1A1 not Correlated with T4
PL&GH-V in CYP±
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.
“We live in a chemical soup”
Is there summation or synergy?
• Ingestion: food, dust, water
• Inhalation: gases, air particles
• Dermal absorption: personal care, dust
• Breast Milk
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 their
environment
Gavin W. ten Tusscher, M.D., Ph.D., paediatrician
Department of Paediatrics and Neonatology
Westfriesgasthuis, Hoorn, Netherlands
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
Toxic Chemicals
Fetus in
Womb /
Child at
Home
Webinar,
24/09/2014
Infant/Child
in Hospital
Gavin ten Tusscher
Child at
Home
26
Sources of exposure to
toxic chemicals in hospitals
Medical Devices
-- IV administration
-- Enteral nutrition
-- Direct contact
-- Inhalation
-- Dermal
Patient —
Infant/Child
Mother
-- Breast
feeding
Webinar,
24/09/2014
Gavin ten Tusscher
Hospital
Environment
-- Inhalation
(air quality)
-- Water
-- Food
-- Dermal
27
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
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24/09/2014
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28
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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24/09/2014
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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
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24/09/2014
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30
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
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Cohort
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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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34
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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24/09/2014
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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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24/09/2014
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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
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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
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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(2ethylhexyl)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)
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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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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”
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24/09/2014
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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
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24/09/2014
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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,
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18/11/2011
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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!
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24/09/2014
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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