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?


“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”


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.



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

Gavin ten Tusscher 25

Overview

– What’s the problem?

– What’s the danger?

– What’s the solution?

Webinar, 24/09/2014


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


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

Webinar, 24/09/2014


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


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

Webinar, 24/09/2014


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


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


Cohort

Webinar, 24/09/2014


Results

Webinar, 24/09/2014


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

Webinar, 24/09/2014


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

Webinar, 24/09/2014


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

Webinar, 24/09/2014


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

Webinar, 24/09/2014


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


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


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


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

Webinar, 24/09/2014


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


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


Not easy …

London, 18/11/2011


London, 18/11/2011


London, 18/11/2011


London, 18/11/2011


London, 18/11/2011


London, 18/11/2011


London, 18/11/2011


London, 18/11/2011


London, 18/11/2011


London, 18/11/2011


London, 18/11/2011


London, 18/11/2011


London, 18/11/2011


Webinar, 24/09/2014


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

Webinar, 24/09/2014


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



Q&A

Date post:	12-Apr-2017
Category:	Health & Medicine
Upload:	des-daughter
View:	861 times
Download:	0 times

Endocrine disruptors in the healthcare sector

Health & Medicine