NON-TOXIC HEALTH CARE: SECOND EDITION (2019) Alternatives to Hazardous Chemicals in Medical Devices: Phthalates and Bisphenol A - Health Care ...

 
NON-TOXIC HEALTH CARE: SECOND EDITION (2019) Alternatives to Hazardous Chemicals in Medical Devices: Phthalates and Bisphenol A - Health Care ...
NON-
TOXIC
HEALTH
CARE:
Alternatives to Hazardous
Chemicals in Medical Devices:
Phthalates and Bisphenol A

SECOND EDITION (2019)
NON-TOXIC HEALTH CARE: SECOND EDITION (2019) Alternatives to Hazardous Chemicals in Medical Devices: Phthalates and Bisphenol A - Health Care ...
TABLE OF CONTENTS
                                                   Foreword												4

                                                   Executive Summary 											5

                                                   Introduction												6

                                                        Hazard of chemicals contained in medical devices   					6

                                                        Hazards for human health      								8

                                                        Exposure through medical devices 								8

                                                        Hazards for the environment									11

                                                        The European legal framework on hazardous chemicals in medical devices         		11

                                                        Why update this report now?									15

                                                   Chapter 1: Substituting hazardous chemicals in Medical Devices					                                          16

                                                        Governmental Initiatives 									17

                                                        Non-Governmental Initiatives 									17

                                                   Chapter 2: Alternatives to phthalates 								19

                                                   Chapter 3: Alternatives to BPA									20

                                                   Chapter 4: Best practices in European healthcare							21

                                                   Chapter 5: The health impact of plastics in healthcare						                                                 22

                                                        General background										22

                                                        Plastics in healthcare - Medical plastics 							28

                                                        Impacts of medical plastics   								29

                                                        Case studies of plastic waste management in European hospitals				32

                                                        Initiatives from the medical devices industry							32

                                                        The way forward / The urgency to act on plastics						34

                                                   Chapter 6: Conclusions and recommendations						                                                             36

                                                        Conclusions											36

                                                        HCWH Europe’s Recommendations								37

                                                   References												39

2   NON-TOXIC HEALTHCARE - SECOND EDITION (2019)                                                                 NON-TOXIC HEALTHCARE - SECOND EDITION (2019)    3
NON-TOXIC HEALTH CARE: SECOND EDITION (2019) Alternatives to Hazardous Chemicals in Medical Devices: Phthalates and Bisphenol A - Health Care ...
FOREWORD                                                                                                          EXECUTIVE SUMMARY

Modern healthcare makes use of a wide range of          HCWH Europe promotes the substitution of harm-            Medical devices play a critical role in healthcare but   Within this report, HCWH Europe examines the
plastic-based medical products to provide high          ful substances by demonstrating that many alter-          may contain hazardous substances in their com-           health impact of plastics in healthcare, and pre-
quality and effective treatment to patients. As a       natives with safer toxicological profiles are available   position that can leach into patients during their       sents a number of recommendations for policy
consequence high volumes of plastic single-use          on the market. We aim to accelerate the shift to-         use and compromise patient safety. Concerns have         makers, competent authorities, notified bodies and
products and complex plastic composites are rou-        wards substitution within the European healthcare         been raised by different societal groups including       healthcare providers, to move towards non-toxic
tinely used by the European health sector and it is     sector, supported by research, evidence, collabo-         governmental bodies, healthcare professionals,           healthcare and minimise the risk to patients wit-
becoming increasingly important to understand the       ration, and greater awareness. Progressive manu-          scientists and civil society organisations, regarding    hout compromising medical care:
impact these materials have on human health.            facturers, governments, health systems, hospitals,        the potential health impacts of chemical exposure
                                                                                                                                                                           l   European legislation must protect the most
We have known for decades that certain hazardous        and health practitioners are starting to come toge-       from medical devices, particularly for vulnerable
                                                                                                                                                                               vulnerable groups. Consistent technical imple-
chemicals leach out of medical devices, such as         ther to lead this change; many European healthca-         population groups.
                                                                                                                                                                               mentation of Annex I.II.10.4 of the MDR must
phthalates in plastic tubing. One of Health Care Wit-   re providers have already moved to eliminate PVC,         In 2017, the European Council adopted the Medical            therefore be ensured. The benefit-risk assess-
hout Harm (HCWH) Europe’s first campaigns focu-         DEHP, and BPA from healthcare practice. HCWH              Devices Regulation (MDR), fully applicable to medi-          ment of the presence of hazardous chemicals
sed on the elimination of DEHP, the most common-        Europe has highlighted a number of examples in            cal devices placed on the EU market as of 26 May             in certain medical devices should therefore be
ly used phthalate, in intravenous drips. Our work in    recent years, some of which are listed in this report.    2020. Importantly, some of the provisions within             subject to the most stringent conformity as-
this area has also highlighted the high exposure to     Importantly, the move towards substitution needs          this regulation have the potential to act as an en-          sessment procedures by a Notified Body
bisphenol A (BPA) of new-borns receiving medical        to be further encouraged and supported by strong          gine for substituting medical devices that contain
treatment using multiple devices.                       political and regulatory action, such as in France for    harmful chemicals with safer alternatives.               l   Devices should be subject to stringent com-
                                                        example, where tubes and pipes containing DEHP                                                                         pliance assessment of required labelling by a
The endocrine-disrupting properties of these che-                                                                 Phthalates and Bisphenol A (BPA) are substances of
                                                        are banned in paediatric, neonatal, and maternity                                                                      Competent Authority. Information labelled in
micals are now well established; we have seen an                                                                  particular concern that are often found in medical
                                                        departments in hospitals. The new Medical Devices                                                                      accordance with the MDR must be accessible
increase in endocrine-related diseases such as bre-                                                               devices. Phthalates are commonly used as plastic
                                                        Regulation introduces provisions that would help                                                                       to the public via the revamped European Data-
ast and testicular cancers, thyroid disorders, infer-                                                             softeners in PVC-based medical devices, whilst BPA
                                                        phase out endocrine disrupting chemicals, carcino-                                                                     base on Medical Devices (EUDAMED)
tility, and diabetes throughout Europe over the last                                                              is used to produce certain plastics such as polycar-
decades.                                                genic, mutagenic and reprotoxic substances, and           bonates and epoxy resins that have applications in       l   The market authorisation process for medical
                                                        particularly phthalates in medical devices, if safer      the medical device industry. A major concern sur-            devices needs increased transparency
This second edition of Non-toxic Healthcare forms
                                                        alternatives are available and technically feasible.      rounding these substances is that they are known
an important part of HCWH Europe’s work to rai-                                                                                                                            l   Sustainable procurement guidelines should
                                                        This is a positive step and one that HCWH Europe          endocrine disrupting chemicals (EDCs), which may
se awareness about the presence of hazardous                                                                                                                                   provide incentives for the substitution of ha-
                                                        will continue to follow and support through its im-       interfere with the normal functioning of the human
substances in medical devices and the consequent                                                                                                                               zardous chemicals in medical devices
                                                        plementation.                                             endocrine system and therefore present a hazard
risks to patients. This report also contains a new
                                                        Prevention is always better than cure, and this the-      to different physiological and developmental pro-        l   Funding for research and development of alter-
chapter specifically examining the health impact of
                                                        me is central to the recommendations laid out in          cesses. EDCs can impact upon the human body                  native substances and products and for clinical
plastics in healthcare.
                                                        this report. Opting for safer alternatives in health-     at very low concentrations and can combine with              and epidemiological projects that compare the
                                                        care to prevent patients (particularly children and       other endocrine disruptors to produce additive ef-           performance of these alternatives should be
                                                        other vulnerable groups), from being exposed to to-       fects. Despite difficulties to demonstrate a causal          prioritised.
                                                        xic chemicals will help prevent devastating lifelong      link, some associations between EDC exposure and
                                                        long-term health consequences in these groups. In         diseases are apparent: evidence shows that foetu-
                                                        doing the healthcare sector will be fulfilling its duty   ses, children, and pregnant women are the most
                                                        to first do no harm.                                      vulnerable groups.
                                                                                                                  Awareness of actions to eliminate harmful plastics
                                                        Will Clark, Executive Director -
                                                                                                                  must be increased within the healthcare sector,
                                                        Health Care Without Harm (HCWH) Europe
                                                                                                                  highlighting that a high level of patient care and
                                                                                                                  safety can be maintained. Furthermore, as some
                                                                                                                  of the most highly trusted community figures, he-
                                                                                                                  althcare professionals have the capacity and moral
                                                                                                                  obligation to educate the communities they serve
                                                                                                                  and help trigger widespread beneficial behaviour
                                                                                                                  changes in plastic use.

4   NON-TOXIC HEALTHCARE - SECOND EDITION (2019)                                                                                                                                         NON-TOXIC HEALTHCARE - SECOND EDITION (2019)   5
NON-TOXIC HEALTH CARE: SECOND EDITION (2019) Alternatives to Hazardous Chemicals in Medical Devices: Phthalates and Bisphenol A - Health Care ...
INTRODUCTION                                                                                                        ment procedures lack integration of endocrinolo-
                                                                                                                    gy concepts, the effects of EDCs in human health
                                                                                                                                                                             exposure can be harmful for patients as they will
                                                                                                                                                                             be primarily from the vulnerable populations and/
                                                                                                                    and the environment are mostly dismissed in the          or maybe rendered more susceptible to toxic insult
                                                                                                                    existing risk assessment framework. In particular,       through (critical) illness. A precautionary approach
                                                                                                                    effects from early life, chronic low-dose, and/or        and eliminating exposure to hazardous chemicals
                                                                                                                    multiple simultaneous exposures are not taken into       wherever possible is therefore appropriate in the
                                                                                                                    consideration. Increased incidence of diseases and       case of medical devices and recognised under the
Medical devices are an essential feature of modern       groups of vulnerable patients that undergo multip-
                                                                                                                    illnesses in humans from neonatal/infancy through
healthcare, playing an important role in prevention,     le medical interventions or are exposed chronically
                                                                                                                    to adulthood has been associated with exposure to
diagnosis, monitoring, and treatment of diseases         over extended periods, including infants in neona-
                                                                                                                    these substances.4 10 In 2015, the Endocrine Society
and disabilities. Hazardous chemicals are often          tal care or dialysis patients.
present in medical devices to improve plastic per-       Substances that are commonly found in medical
                                                                                                                    reviewed the latest science and declared that the
                                                                                                                    evidence for adverse reproductive effects is strong
                                                                                                                                                                                 BOX 2
formance e.g. plasticisers, flame-retardants, fillers,   devices and are of particular concern are phthala-         and mounting for effects in areas such as neuroen-           What are phthalates?
colourings, impact modifiers, and stabilisers. These     tes and Bisphenol A (BPA). These substances have           docrine, sexual development, obesity, metabolism,
harmful chemicals can represent a high percentage        been the subject of intense political debate in re-                                                                     Phthalates are a group of chemical substan-
                                                                                                                    thyroid systems, and insulin resistance. Further, the
of the final product (in some case up to 80%) and        cent years due to their widespread use in consu-                                                                        ces, primarily used as plasticisers (softeners) in
                                                                                                                    effects may also be transmitted to future generati-
can leach out of products and have adverse effects       mer products and the risks they pose to human                                                                           plastics to make them more flexible. Depen-
                                                                                                                    ons.11
on human health and the environment.                     health and the environment. The endocrine-dis-                                                                          ding on the number of carbon atoms in their
                                                                                                                    A European Parliament study reviewed the scienti-
Concerns regarding hazardous chemical exposure           rupting properties of these chemicals are also well                                                                     alkyl side-chains they are divided into:
                                                                                                                    fic evidence of endocrine disruption, the extent of
through medical devices are particularly relevant to     established.
                                                                                                                    EDC exposure, and the associated health effects              l    High-chain length - with more than six car-
                                                                                                                    and consequent costs of treatment. Published in                   bons (e.g. DINP, DIDP, DPHP, and DIUP)
                                                         Hazard of chemicals contained in medical                   May 2019, the study concluded that after several
                                                                                                                                                                                 l    Transitional-chain length - with three to six
BOX 1                                                    devices                                                    decades of multidisciplinary research in endocrino-
                                                                                                                    logy, ecotoxicology, toxicology, epidemiology, clini-
                                                                                                                                                                                      carbons (e.g. DEHP, DBP, DIBP and BBP)
                                                         Humans are exposed to environmental contami-               cal research, epigenetics, environmental sciences            l    Low-chain length - fewer than three car-
EU definition of a medical device                        nants from several sources and exposure pathways,          and other disciplines, endocrine disruption is now                bons. (e.g. DEP and DMP)
(Regulation 2017/745 on medical devices1)                including consumption of contaminated food and             an important and validated scientific concept.12 The         Phthalates are abundant in polyvinyl chloride
                                                         water, air and dust inhalation/ingestion, and dermal       evidence therefore justifies classifying EDCs as a
Any instrument, apparatus, appliance, software,                                                                                                                                  (PVC) medical devices such as blood bags, in-
                                                         absorption. Human biomonitoring studies have de-           specific class of hazard, equivalent to that of car-
implant, reagent, material, or other article inten-                                                                                                                              travenous bags, tubing, catheters, respiratory
                                                         tected hazardous chemicals like phthalates and             cinogenic, mutagenic, reprotoxic chemicals (CMRs).
ded by the manufacturer to be used, alone or in                                                                                                                                  masks, or disposable gloves - approximately
                                                         BPA in almost every individual analysed and in a va-
combination, for human beings for one or more                                                                       Researchers and healthcare practitioners are par-            40% of all plastic-based medical devices are
                                                         riety of human tissues and fluids such as placental
of the following specific medical purposes:                                                                         ticularly concerned that exposure to EDCs from               made from PVC.13
                                                         tissue, breast milk, amniotic fluid, urine, blood, cord
                                                                                                                    medical devices compounds adds to the existing               Di-2-ethylhexyl phthalate (DEHP) has for many
l    Diagnosis, prevention, monitoring, predic-          blood, sperm, and saliva.2 3 4 5 6 7 8 9 The majority of
                                                                                                                    exposure from other sources: EDCs are ubiquitous             years been the most commonly used phthala-
     tion, prognosis, treatment, or alleviation of       studies show widespread exposure to phthalates
                                                                                                                    and the entire population is already exposed. Furt-          te ester plasticiser in medical devices. A 2014
     disease                                             in unborn children and infants across Europe. The
                                                                                                                    hermore, vulnerable population groups such as                survey in the Danish Medical Device Industry
l    Diagnosis, monitoring, treatment, allevia-          new European Human Biomonitoring (HBM4EU)
                                                                                                                    neonates, infants, pregnant and breast-feeding wo-           found that 95% of products contained DEHP.14
     tion of, or compensation for, an injury or          Initiativei (2017-2021) aims to coordinate and ad-
                                                                                                                    men, and the elderly are not adequately protected            DEHP can contribute up to 40% of weight of
     disability                                          vance human biomonitoring in Europe. The project
                                                                                                                    from the risk of exposure to these chemicals. The            intravenous bags and up to 80% of weight in
                                                         represents a joint effort of Members States, the
l    Investigation, replacement or modifica-                                                                        most at risk groups comprises dialysis patients and          medical tubing.15 Leaching of DEHP from PVC
                                                         European Environment Agency, and the European
     tion of the anatomy or of a physiological                                                                      neonates in intensive care units, as they experien-          medical devices has been documented since
                                                         Commission. One of the objectives of HBM4EU is to
     or pathological process or state                                                                               ce frequent and intimate contact with a number of            the late 1960s.16 17 18 Use of PVC medical de-
                                                         generate scientific evidence on the causal relation-
                                                                                                                    medical devices containing EDCs. Premature babies            vices may lead to a higher exposure to DEHP
l    Providing information by means of in vitro          ships between exposure to prioritised chemicals
                                                                                                                    and infants are particularly sensitive to phthalate          than everyday sources affecting the general
     examination of specimens derived from               (including phthalates and bisphenols) and the ad-
                                                                                                                    effects, as their reproductive system is still develo-       population.19
     the human body, including organ, blood,             verse health effects and public health implications.
                                                                                                                    ping and they have much higher relative phthalates
     and tissue donations                                One of the major reasons for concern surrounding           intakes. In addition, the unborn and young children
This does not include devices/treatments that            phthalates and BPA is that they are known endo-            are not able to metabolise chemical substances in
achieve the principal intended action by phar-           crine disrupting chemicals (EDCs) that can mimic           the same way as adults, due to the on-going de-
macological, immunological or metabolic me-              or otherwise interfere with hormone production or          velopment of their organs and maturation of the
ans, in or on the human body, but a medical              function. EDCs can therefore interfere with organ          different systems (see Box 5).
device may be assisted in its function by such           formation and growth, sexual maturation, stress re-
                                                                                                                    Despite claims that exposure to hazardous chemi-
means.                                                   sponse, and behaviour.10 As traditional risk assess-
                                                                                                                    cals through medical devices represents a small
                                                                                                                    proportion of an individual’s overall exposure, this
                                                         i www.hbm4eu.eu

6   NON-TOXIC HEALTHCARE - SECOND EDITION (2019)                                                                                                                                           NON-TOXIC HEALTHCARE - SECOND EDITION (2019)   7
NON-TOXIC HEALTH CARE: SECOND EDITION (2019) Alternatives to Hazardous Chemicals in Medical Devices: Phthalates and Bisphenol A - Health Care ...
higher risk of male reproductive disorders after            the potential human health risks posed by DEHP in        multiple medical devices simultaneously, sequenti-
                                                       prenatal and postnatal exposure to phthalates.25 It         medical devices.                                         ally, or intermittently.50 51 Neonates in intensive care
BOX 3                                                  has been proven that phthalates can transfer from           According to the SCENIHR premature neonates in           are exposed to DEHP at much higher levels than
                                                       mothers to foetuses and neonates through placen-            neonatal intensive care units, infants subjected to      existing safe limits, which might contribute to com-
What is Bisphenol A?                                   ta and breast milk.26 Exposure to DEHP and DBP              repeated medical treatment using medical devices,        mon early and chronic complications of prematu-
                                                       has been linked with reproductive alteration inclu-         and patients undergoing haemodialysis are at risk        rity.52
Bisphenol A (4,4-dihydroxy-2,2-diphenylpropa-          ding low sperm concentration, shortened anogeni-            of DEHP-induced effects.19 Patients in a neonatal        Premature infants in neonatal intensive care units
ne or BPA) is a chemical substance used as a           tal distances (a measure of feminisation of exter-          intensive care unit (NICU) are exposed to phthalate      undergoing treatment were also found to have BPA
monomer in the production of polymers such             nal genitalia), endometriosis, hypospadias, shorter         mixtures through the complex materials used con-         levels 10 times higher than the general population,
as polycarbonate, epoxy resins, polysulfone,           pregnancy duration, changes in neurobehaviour in            currently in NICU care: respiratory circuits, intrave-   presumably from BPA leaching from medical devi-
and polyacrylate. BPA is also used as an an-           neonates, infants and children, cholestasis, derma-         nous equipment, enteral feeding supplies, and in-        ces.53 Infants in neonatal intensive care units using
tioxidant and inhibitor in the polymerisation          titis, heart disease and perturbations in inflamma-         cubators are likely vehicles of phthalate exposure.46    a large number of PVC-containing medical devices
of PVC and as a precursor for the synthesis of         tory responses.27 28 29 30 31 32 A recent comprehensive
                                                                                                                   Whilst evidence of BPA leaching into patients is         had also higher concentrations of urinary BPA (one
the flame retardant tetrabromobisphenol A              and critical review addressed the health hazards
                                                                                                                   more limited, dialysers, dental materials, circula-      order of magnitude higher than the median con-
(TBBPA). Up to 1 million tonnes of BPA is ma-          posed by phthalates on children and adolescents,
                                                                                                                   tion equipment, neonatal care medical devices,           centration of the general population in the US).54
nufactured and/or imported in the European             including reproductive toxicity in women and men,
Economic Area (EEA) annuallyiii, from which                                                                        and urinary catheters have demonstrated releases         Recent clinical studies provide information about
                                                       cancer, insulin resistance and type II diabetes, over-
over 95% of BPA is used in the production of                                                                       of BPA.23 Length of contact time (duration of expo-      the overall significant exposure to BPA during hae-
                                                       weight and obesity, allergy and asthma.6 Growing
polycarbonates and epoxy resins.20 21                                                                              sure), temperature and pH, among other parame-           modialysis treatment in patients suffering from
                                                       evidence suggests that prenatal phthalate exposu-
                                                                                                                   ters, has been shown to increase the release of BPA      end-stage renal disease (ESRD).55 A recent study de-
BPA has applications in medical devices that           res may have neurodevelopmental consequences33
                                                                                                                   from polycarbonate.23 The SCENIHR opinion on the         monstrated overexposure to BPA and its chlorina-
have both direct and indirect contact with pa-         34 35 36
                                                                and can affect IQ, attention, hyperactivity, and
                                                                                                                   safety of the use of Bisphenol A in medical devices      ted derivatives of patients with ESRD during online
tients including those made of polycarbonate,          social communication of children.37 38
                                                                                                                   concluded that there is a risk when BPA is directly      haemodiafiltration (OL-HDF) due to BPA leaching
polysulfone, and PVC such as medical tubing,           Exposures to BPA are associated with many health            available for systemic exposure after non-oral ex-       from different medical devices.56
catheters, haemodialysers, newborn incuba-             effects in humans, including reproductive effects           posure routes, especially for neonates in intensive      The materials used in medical devices are also an
tors, syringes and blood oxygenators. BPA has          (erectile dysfunction, miscarriage), cardiovascular         care units, infants undergoing prolonged medical         important factor. In one study, BPA concentrations
been shown to leach from medical devices               diseases, thyroid, immune and metabolic diseases            procedures, and for dialysis patients.23 The risk of     among infants in one healthcare unit were approxi-
into liquids.22 23 European PVC manufacturers          (diabetes), childhood obesity as well as general/ab-        adverse effects due to BPA may exist in patients un-     mately 17 times higher than another unit.54 Patients
informed the Scientific Committee on Emer-             dominal obesity and hypertension, neurodevelop-             dergoing dialysis treatment since BPA accumulates        undergoing regular continuous ambulatory peri-
ging and Newly Identified Health Risks (SCE-           ment impairments, respiratory conditions and                in systemic circulation due to reduced renal clea-       toneal dialysis using plasticiser-free devices had
NIHR) that they no longer use BPA as stabiliser        behaviour alterations (anxiousness, hyperactivity,          rance. Although the benefit of medical devices has       reduced levels of phthalates in urine and blood.57
or antioxidant in PVC production.23                    depression).39 40 41 42 43 BPA has recently also been       also to be considered, the SCENIHR recommends            Moreover, the level of cholestasis in neonates was
                                                       suggested to be an emerging threat to male infer-           that, where practical, medical devices that do not
ii https://echa.europa.eu/                                                                                                                                                  reduced from 50% to 13% in neonates fed through
                                                       tility.44                                                   leach BPA should be used.23 With the exception of        a DEHP-free catheter.58
                                                       Particularly worrying is the fact that exposure to          dialysis patients (for which treatment is repeated
                                                                                                                                                                            A growing number of studies suggest the link bet-
                                                       phthalates and Bisphenol A can lead to cumulative           over long time periods and can be considered si-
                                                                                                                                                                            ween exposure of patients to phthalates and/or
Hazard for human health                                adverse effects on future generations such as neu-          milar to chronic exposure), the exposure to BPA via
                                                                                                                                                                            BPA from medical devices and adverse effects in
                                                       ral and immune disorders, infertility, and late-onset       medical devices is generally of limited duration (re-
There is growing evidence that many phthalates                                                                                                                              exposed patients. There is emerging evidence that
                                                       complex diseases (cancers and diabetes).45                  presentative of acute to sub-chronic exposure in a
and BPA can present a hazard to human health and                                                                                                                            the use of medical devices containing DEHP is po-
                                                                                                                   toxicological context).
are recognised in the EU as endocrine-disrupting                                                                                                                            tentially harmful for the brain development and
                                                       Exposure through medical devices                            A number of observations from the scientific lite-       function of critically ill children. Belgian clinicians
compounds. Evidence comes from in vitro and ani-
                                                                                                                   rature are available, confirming the link between        identified a clear link between previously hospita-
mal studies as well as clinical and epidemiological
                                                       Exposure to hazardous chemicals through medi-               use of plastics in medical devices and exposure of       lised children’s long-term neurocognitive test re-
studies encompassing both prenatal and postnatal
                                                       cal devices can be enteral (via the digestive tract),       patients to phthalates and/or BPA. A strong asso-        sults and their individual exposure to the phthalate
exposures.
                                                       parenteral (intravenously), transcutaneous (via the         ciation was found between the use of DEHP-contai-        DEHP during their stay in intensive care.59 Critically
The effects of DEHP in animals has been thoroughly     skin), or through inhalation. Dietary exposure to           ning medical devices and urinary concentrations of       ill children had very high circulating levels of phtha-
reviewed by Scientific Committee on Emerging and       phthalates and BPA is expected to account for the           three DEHP metabolites in infants receiving care in      late metabolites, explained by leaching from medi-
Newly Identified Health Risks (SCENIHR)19 which        majority of human exposure. Several studies have            two neonatal intensive care units.47 DEHP leached        cal devices, and these levels were associated with
concluded that i) the testis toxicity of DEHP is age   described phthalates, (particularly DEHP), leaching         from endotracheal tubes immediately after use in         the significant attention-deficit observed four years
dependent, with immature animals being more            from medical devices and recorded levels in uri-            high-risk neonates.48 Premature neonates receiving       later.
susceptible to testicular toxicity by DEHP than ol-    ne and blood. The leaching of DEHP from medical             treatment through feeding tubes and endotracheal
der mature animals; ii) even low-level exposures to                                                                                                                         Another recent study highlighted the impact of acu-
                                                       plastic devices into body fluids and subsequent mi-         tubes had increased levels of DEHP in their urine.49
DEHP during pregnancy can affect male genital de-                                                                                                                           te mono-2-ethylhexyl phthalate (MEHP, the primary
                                                       gration into human tissues was first reported in the        Certain vulnerable patients groups such neonates
velopment.24                                                                                                                                                                metabolite of DEHP) exposure on cardiac electrop-
                                                       late 1960s.16 Nearly 60 years after this discovery,         / children are exposed during intense care to mul-       hysiology in the heart. It concluded that heightened
A review of human epidemiology studies found a         regulators are still struggling to define and manage        tiple invasive medical procedures and therefore to

8   NON-TOXIC HEALTHCARE - SECOND EDITION (2019)                                                                                                                                           NON-TOXIC HEALTHCARE - SECOND EDITION (2019)   9
NON-TOXIC HEALTH CARE: SECOND EDITION (2019) Alternatives to Hazardous Chemicals in Medical Devices: Phthalates and Bisphenol A - Health Care ...
clinical exposure to plasticised medical products                                                                                                                    periments and in vitro studies show that exposure
might have cardiac safety implications.60 Several                                                                                                                    to environmentally relevant concentrations of BPA
clinical observations point to the possible involve-       BOX 4                                            BOX 5                                                    have shown detrimental effects in invertebrates
ment of BPA/DEHP exposure in dialysis patients in-                                                                                                                   and all vertebrate classes.63 Similarly, exposure to
creased cardiovascular (CV) mortality and sudden           Medical procedures with potential                Why neonates and children are more                       different phthalates and/or their metabolites has
cardiac death (SCD).61 As emphasised by the aut-           for high exposure to DEHP19 and BPA23            vulnerable                                               caused adverse effects at various endpoints in
hors, importantly, BPA/DEHP exposure may be a                                                                                                                        aquatic organisms at environmentally relevant ex-
modifiable risk factor for SCD in dialysis as alternati-   l    Exchange transfusion of blood in neon-      The levels of exposure to hazardous chemi-               posures.67 There are studies that indicate that BPA
ves to BPA and DEHP do exist and could potentially              ates                                        cals are of particular concern for unborn chil-          can especially affect development, reproduction,
be used as replacements for dialysis procedures.                                                            dren, neonates, and children. These groups               immune function and metabolism in aquatic speci-
                                                           l    Extracorporeal membrane oxygenation
Replacement of BPA- and DEHP-leaching plastics                                                              are being exposed to hazardous chemicals at              es.68 Besides the chemical contamination of a wide
                                                                (ECMO) treatment of neonates and of
may reduce morbidity and mortality of patients with                                                         a highly vulnerable moment when important                range of natural habitats, these compounds also
                                                                adults
ESRD undergoing dialysis and of other patients un-                                                          aspects of their development can be altered,             create a waste management problem. The disposal
dergoing invasive interventions with prolonged ex-         l    Total Parenteral Nutrition (TPN) in neon-   perhaps with lifelong consequences. Further-             of PVC medical waste can release dioxins and ot-
posure to plastics (e.g. cardiac surgery). Prospective          ates                                        more, their low body weight means the expo-              her persistent environmental pollutants, which can
clinical studies and randomised controlled trials are      l    Multiple procedures in sick neonates        sure can be relatively higher than for adults.           have a detrimental impact on human health and
needed to test this hypothesis.                                                                             Premature babies are subject to an even hig-             the environment.
                                                           l    Haemodialysis                               her risk due to their lower birth weight com-
These data strongly support SCENIHR’s recommen-
dation to use medical devices with low DEHP and            l    Enteral nutrition in neonates and adults    bined with the fact they require many medi-
                                                                                                                                                                     The European legal framework on hazar-
BPA release potential, whenever possible.                                                                   cal interventions. In addition, the unborn and
                                                           l    Heart transplantation or coronary artery                                                             dous chemicals in medical devices
                                                                                                            young are not able to metabolise chemical
                                                                bypass graft surgery                        substances in the same way as adults, due to             European medical devices manufacturers have to
                                                           l    Massive blood transfusion of red blood      the on-going development of their organs and             comply not only with the EU Medical Devices Re-
                                                                cells and plasma                            maturation of the different systems. For exam-           gulation 2017/745 but also with a number of che-
                                                                                                            ple, the glucuronidation mechanisms that are             mical regulations – the EU Regulation 1907/2006
                                                           l    Peritoneal dialysis
                                                                                                            responsible for the excretion of some phthala-           on the Registration, Evaluation, Authorisation and
                                                           Six scenarios considered as representative       te metabolites are not fully developed before            Restriction of Chemicals (REACH) and the EU Direc-
                                                           situations of release of BPA from medical de-    the age of 3 months.3 Finally, expected longer           tive 2011/65/EU on the Restriction of Hazardous
                                                           vices:                                           life spans could mean that this group will be            Substances in Electrical and Electronical Equipment
                                                           1.   External contact with a medical device      exposed for a longer time to these substan-              (RoHS II).
                                                                containing BPA                              ces. All these factors may put this group at an
                                                                                                            increased risk of suffering deleterious effects.
                                                           2.   Contact with oral/dental material and/or                                                             The REACH Regulation
                                                                orthodontic equipment
                                                                                                                                                                     The REACH regulation makes a distinction between
                                                           3.   Contact with implants such as valves,                                                                medical devices that are:
                                                                pacemakers and insulin dispensers made      Hazards for the environment
                                                                from polycarbonate                                                                                   l   Chemical substances, either on their own or
                                                                                                            Phthalates and BPA have been detected in aquatic
                                                                                                                                                                         as mixtures. Examples of mixtures include lu-
                                                           4.   Haemodialysis                               and marine environments, terrestrial ecosystems
                                                                                                                                                                         bricants, dental filling materials and bone ce-
                                                                                                            and in the atmosphere in concentrations that are
                                                           5.   Prolonged surgical procedures such as                                                                    ments.
                                                                                                            likely to adversely affect a number of species.62 63
                                                                bypass operations and transplantations                                                                   Articles (that is, objects with a function deter-
                                                                                                            These substances have also been shown to bioac-          l
                                                           6.   Prolonged exposure to different sources     cumulate in some species of molluscs and crusta-             mined by their shape, surface or design rather
                                                                of BPA in intensive care units.             ceans.64 Phthalates have been measured in a range            than their chemical composition (Article 3.3).
                                                                                                            of environmental matrices, including sludge, dust,           Examples include catheters, contact lenses
                                                                                                            soil, air, and water, and are ubiquitous contami-            and medical implants.
                                                                                                            nants in the environment. Phthalates and BPA can         In practice, most medical devices are likely to quali-
                                                                                                            reach the environment from industrial discharges,        fy as articles under REACH.
                                                                                                            sewage, landfill leachates and natural breakdown of
                                                                                                                                                                     A medical device that qualifies as a substance/
                                                                                                            plastics in the environment.
                                                                                                                                                                     mixture is subject to most of the requirements of
                                                                                                            DEHP (authorisation list)65 and BPA (candidate list)66   REACH, including registration. Pursuant to Articles
                                                                                                            are both classified by the European Commission as        60(2) and 62(6) of REACH, an application for aut-
                                                                                                            “toxic to aquatic life with long lasting effects” and    horisation is not required for a substance used in
                                                                                                            endocrine disrupting chemical for environment.           a medical device. Article 60(2) states that the Com-
                                                                                                            Data collected from wildlife studies, laboratory ex-     mission shall not consider the risks to human health

10   NON-TOXIC HEALTHCARE - SECOND EDITION (2019)                                                                                                                                 NON-TOXIC HEALTHCARE - SECOND EDITION (2019)   11
NON-TOXIC HEALTH CARE: SECOND EDITION (2019) Alternatives to Hazardous Chemicals in Medical Devices: Phthalates and Bisphenol A - Health Care ...
arising from the use of a substance in a medical de-                  European Parliament.                                    Phthalates in the Authorisation List65
vice regulated by the MDR. Nonetheless, suppliers,                    In the case of BPA, this has been classified as toxic
distributors or retailers of medical devices have the                 for reproduction, an EDC for human health and an
duty to communicate information about the pre-                        EDC for environment, and listed on the Candidate          Phthalate                            CAS number               Reason for inclusion
sence of Substances of Very High Concern – SVHCs                      List of SVHCs under REACH in 2017. However, Plas-
if requested by a consumer in 45 days (Article 33).                   ticsEuropeiiii (the leading pan-European industrial       DIPP: Diisopentyl phthalate          CAS 605-50-5             Toxic for reproduction
Several phthalates are classified as toxic for repro-                 association) brought a case to the EU court against
duction under the EU Regulation (EC) No 1272/2008                     BPA's classification as a SVHC and against the iden-
                                                                                                                                DIBP: Diisobutyl phthalate           CAS 84-69-5              Toxic for reproduction; Endocrine disrup-
on the classification, labelling and packaging of sub-                tification of BPA as an endocrine disruptor with im-
                                                                                                                                                                                              ting properties for human health
stances and mixtures (the CLP Regulation) and are                     pact on health. This year, the General Court of the
listed on the Candidate List of SVHCs under REACH                     EU dismissed both claims. PlasticsEurope also chal-
(see Table 1). Seven of those phthalates had subse-                   lenged the identification of BPA as an endocrine          BBP: Benzylbutyl phthalate           CAS 85-68-7              Toxic for reproduction; Endocrine disrup-
quently been added to the Authorisation List (An-                     disruptor with impact on the environment in a third                                                                     ting properties for human health
nex XIV of REACH) due to their classification as toxic                case (the judgment is expected in November 2019).
for reproduction (see Table 1).                                                                                                 DEHP: Bis(2-ethylhexyl) phtha-       CAS 117-81-7             Toxic for reproduction; Endocrine disrup-
The European Chemicals Agency (ECHA) has recent-                      iii https://www.plasticseurope.org/en                     late                                                          ting properties for human health; Endocri-
ly submitted a recommendation to the European                                                                                                                                                 ne disrupting properties for environment
Commission to amend Authorisation List entries
by adding the endocrine disrupting properties of                                                                                DBP: Dibutyl phthalate               CAS 84-74-2              Toxic for reproduction; Endocrine disrup-
DEHP, BBP, DBP, and DIBP.69 They were identified                                                                                                                                              ting properties for human health
as substances of very high concern (SVHCs) due to
endocrine disrupting properties with effects on hu-
man health. DEHP was also identified for its effects                                                                            PIPP: n-pentyl-isopentyl phtha-      CAS 776297-69-9          Toxic for reproduction
on the environment. One important impact of this                                                                                late
is that the REACH authorisation process will be able
to address – and work to phase out in the longer                                                                                DMEP: Bis(2-methoxyethyl)            CAS 117-82-8             Toxic for reproduction
term – the use of DEHP in medical devices. The aut-                                                                             phthalate
horisation process places significant emphasis on
the substitution of affected substances. The actual
amendment of the entries including the final deci-
sion on the dates, by which companies will need to
apply for authorisation to ECHA and on exemptions                                                                             RoHS II Directive                                        tion cycles for medical devices and monitoring and
of uses, will be made by the European Commission                                                                                                                                       control instruments were taken into account while
                                                                                                                              The RoHS II Directive (2011/65/EU) was adopted to        determining the transitional period. Consequently,
in collaboration with the Member States and the
                                                                                                                              limit the concentration of six hazardous substances      the restriction of the use of DEHP, BBP, DBP and
                                                                                                                              (including lead, mercury and toxic flame retardants)     DIBP applies to medical devices, including in vitro
TABLE 1                                                                                                                       in electrical and electronic equipment with a view       medical devices, and monitoring and control instru-
                                                                                                                              to contributing to the protection of human health        ments, including industrial monitoring and control
Phthalates in the Candidate List of Substances of Very High Concern (REACH)66                                                 and the environment. From July 2014, the RoHS II         instruments, from 22 July 2021.
                                                                                                                              Directive also applies to electrical and electronic
                                                                                                                              medical devices. In vitro medical devices are cove-
     Phthalate                                       CAS number                Reason for inclusion                           red from July 2016 and active implantable medical        The Medical Devices Regulation (MDR)
                                                                                                                              devices are exempted. Additional exemptions have
                                                                                                                                                                                       The new MDR aims to create a modernised and
     DCHP (Dicyclohexyl phthalate)                   84-61-7                   Toxic for reproduction; Endocrine disrup-      been added (Annex IV), specific to medical devices
                                                                                                                                                                                       more robust EU legislative framework to ensure
                                                                               ting properties for human health               and monitoring and control instruments for which
                                                                                                                                                                                       better protection of public health and patient safety
                                                                                                                              a reliable alternative was not available.
                                                                                                                                                                                       and include, among others, stronger rules on clini-
     DHP (Dihexyl phthalate)                         84-75-3                   Toxic for reproduction                         Directive (EU) 2015/863 (often referred to as "RoHS      cal and performance evaluation, reinforced desig-
                                                                                                                              3") amends Directive 2011/65/EU adding four sub-         nation and oversight processes of Notified Bodies,
                                                                                                                              stances to the original six restricted substances        establishment of a comprehensive EU database on
     DPP (Dipentyl phthalate)                        131-18-0                  Toxic for reproduction
                                                                                                                              – Bis(2-ethylhexyl) phthalate (DEHP), Butyl benzyl       medical devices (EUDAMED) to be made publicly
                                                                                                                              phthalate (BBP), Dibutyl phthalate (DBP) and Dii-        available, and stricter requirements related to the
     1,2-benzenedicarboxylic acid,                   CAS 84777-06-0            Toxic for reproduction                         sobutyl phthalate (DIBP) – in view of their negati-      use of hazardous substances. When the MDR takes
     dipentylester, branched and                                                                                              ve impact on recycling and on human health and           effect in May 2020, manufacturers will have to com-
     linear                                                                                                                   the environment during electrical and electronic         ply with new rules for almost every kind of product
                                                                                                                              waste management operations. The longer innova-

12    NON-TOXIC HEALTHCARE - SECOND EDITION (2019)                                                                                                                                                  NON-TOXIC HEALTHCARE - SECOND EDITION (2019)   13
NON-TOXIC HEALTH CARE: SECOND EDITION (2019) Alternatives to Hazardous Chemicals in Medical Devices: Phthalates and Bisphenol A - Health Care ...
in the medical device spectrum.                                                                                     cess will be extended. The database will not only be      Why update this report now?
According to the new EU Medical Devices Regula-                                                                     used by the Competent Authorities and the Euro-
tion, “Devices shall be designed and manufactured in           BOX 6                                                pean Commission, it will also be accessed by the          Many alternative substances and materials have
                                                                                                                                                                              appeared in recent years for many of the most
such a way as to reduce as far as possible the risks po-                                                            Medical Devices Coordination Group (MDCG), No-
                                                                                                                    tified Bodies, Economic Operators (manufacturers,         hazardous chemicals used in medical devices, in-
sed by substances or particles, including wear debris,         Regulation (EU) 2017/745, Annex
                                                                                                                    authorised representatives, importers, sponsors),         cluding for phthalates and BPA. There is a choice
degradation products and processing residues, that             I.II.10.4 (Substances: 10.4.1. Design
                                                                                                                    experts, and the public, including medical instituti-     now to be made between safer alternatives or ig-
may be released from the device.”                              and manufacture of devices):
                                                                                                                    ons.                                                      noring the potential dangers to patients. The new
Annex I.II.10.4 of the MDR introduces provisions               Devices, or those parts thereof, or those ma-                                                                  European legislation was long in the making, but
that would help phase out endocrine disrupting                                                                      Creating greater transparency will allow for a better
                                                               terials used therein that:                                                                                     with the MDR there is a real opportunity to accele-
chemicals (EDCs), carcinogenic, mutagenic and re-                                                                   understanding of what medical devices are placed
                                                                                                                                                                              rate the process of phasing-out phthalates and BPA
protoxic substances (CMRs), and phthalates in me-              l    Are invasive and come into direct contact       on the EU market and who is ultimately responsi-
                                                                                                                                                                              and minimise patients, and in particular vulnerable
dical devices if safer alternatives are available and               with the human body                             ble for them. The level of access, however, will differ
                                                                                                                                                                              groups, exposure to these harmful chemicals.
technically feasible. Manufacturers of medical de-                                                                  between the types of user.
                                                               l    (Re)administer medicines, body liquids                                                                    We are all exposed to endocrine disrupters from
vices are required to provide adequate justification                or other substances, including gases, to/       Theoretically, procurers (such as hospitals and Com-
                                                                                                                                                                              multiple sources, but healthcare should not be one
(benefit-risk assessment) to the Notified Body for                  from the body, or                               petent Authorities) will be able to access, search,
                                                                                                                                                                              of these. As Kambia and co-authors stated already
the presence of those substances if they are pre-                   transport or store such medicines, body         and filter the content of EUDAMED to identify safer
                                                                                                                                                                              more than fifteen years ago, when exposures to
sent above a certain concentration (see Box 6). The                 fluids or substances, including gases, to       medical devices for their procurement process.
                                                                                                                                                                              hazardous chemicals in medical devices can be
term “notified body” refers to the typically private                be (re)administered to the body                 Originally, the new database’s launch was suppo-          avoided through careful selection of materials,
companies charged with evaluating the quality and                                                                   sed to coincide with the date of application for the
                                                                Shall only contain the following substances                                                                   not doing it is both unprofessional and undesi-
safety of medical devices in the EU.                                                                                MDR in May 2020. However, in October 2019, the
                                                                in a concentration that is above 0,1 % w/w                                                                    rable.71
The Scientific Committee on Health, Environmen-                                                                     Commission announced that the launch would be
                                                                where justified:
tal and Emerging Risks (SCHEER) of the European                                                                     delayed by two years. The Commission plans to
Commission prepared the Guidelines on the benefit-             l    Category 1 Carcinogen, Mutagen, Repro-          have the new database ready when another piece
risk assessment of the presence of phthalates in certain            ductive Toxins (CMRs)                           of legislation — the in vitro diagnostics regulation —
medical devices covering phthalates, which are carci-          l    Endocrine disrupting chemicals                  comes into full effect in May 2022.
nogenic, mutagenic, and toxic to reproduction (CMR)
or have endocrine disrupting (ED) properties.70
Before a justification can be accepted as valid, seve-
ral steps need to be taken, including giving conside-      The presence of hazardous substances (subject to
ration to the possible use of alternative substances,      justification) will have to be indicated on the me-
materials, designs, and medical treatments. In ad-
dition, the risk in terms of hazards associated with
                                                           dical devices’ labelling (in accordance with provisi-
                                                           ons laid down in Annex I.II.10.4.5). It also specifies
                                                                                                                    BOX 7
such alternatives should be weighed against the            that, if such devices are intended to treat children
                                                           or pregnant or nursing women, the manufacturer           Regulation (EU) 2017/745, Annex
risk of the use of CMR 1A/1B and/or ED identified
                                                           should provide information on residual risks for         I.II.10.4 (Substances: 10.4.5. Labelling):
phthalates covered under MDR Annex I Chapter II
point 10.4.1. However, the risk by itself is not the       these patient groups and if applicable on appro-         Where devices, parts thereof or materials used
only parameter to consider; an evaluation must             priate precautionary measures (see Box 7).               therein as referred to in Section 10.4.1. con-
also be made of the impact of the possible alter-          Information labelled in accordance with this annex       tain substances referred to in points (a) or (b)
natives on the functionality, the performance and          is one of the mandatory Unique Device Identifiers        of Section 10.4.1. in a concentration above 0,1
the overall benefit-risk ratio of the medical device.      (UDI) data elements to be provided by the manu-          % weight by weight (w/w), the presence of tho-
These Guidelines are intended to be used by the            facturer to the UDI database. This information on        se substances shall be labelled on the device
relevant stakeholders, e.g. manufacturers, notified        the devices will be accessible to the public via the     itself and/or on the packaging for each unit
bodies and regulatory bodies. The approach taken           European Database on Medical Devices (EUDA-              or, where appropriate, on the sales packaging,
in these Guidelines may also be used for a benefit-        MED).                                                    with the list of such substances.
risk assessment of other CMR/ED substances pre-            EUDAMED’s purpose is to strengthen market sur-           If the intended use of such devices includes
sent in medical devices. As foreseen by the MDR,           veillance and transparency in the field of medical       treatment of children or treatment of preg-
adherence to these Guidelines will become man-             devices, by providing national Competent Authori-        nant or breastfeeding women or treatment of
datory.                                                    ties with fast access to information. EUDAMED in         other patient groups considered particularly
                                                           current form contains data on medical devices that       vulnerable to such substances and/or materi-
                                                           have been collected and entered by Competent             als, information on residual risks for those pa-
                                                           Authorities and the European Commission and is           tient groups and, if applicable, on appropriate
                                                           currently only accessible by these parties. The MDR,     precautionary measures shall be given in the
                                                           however, calls for EUDAMED to be revamped: the           instructions for use.
                                                           information will be more comprehensive and ac-

14   NON-TOXIC HEALTHCARE - SECOND EDITION (2019)                                                                                                                                          NON-TOXIC HEALTHCARE - SECOND EDITION (2019)   15
NON-TOXIC HEALTH CARE: SECOND EDITION (2019) Alternatives to Hazardous Chemicals in Medical Devices: Phthalates and Bisphenol A - Health Care ...
CHAPTER 1

Substituting hazardous chemicals in medical devices

Exposure to phthalates or BPA can be minimised                                                                                                                        and maternity departments in hospitals in France.
by adopting a precautionary approach and repla-                                                                                                                       This law also paves the way for a future ban on
cing medical devices with phthalate-free and BPA-         BOX 8                                                                                                       DEHP and other phthalates in all medical devices
free devices, which can fulfil the same function. The                                                          Progress made by the industry                          if alternative materials are available and the equip-
precautionary principle is enshrined in Article 191       PVC-free Blood Bag project                                                                                  ment’s safety can be guaranteed.
of the Treaty on the Functioning of the European                                                               Eastman Chemical Company has teamed up
                                                                                                                                                                      The French National Agency for the Safety of Medi-
Union (EU) and aims to ensure a high level of en-         The PVC-free Blood Bag Project (www.pvcfree-         with BloodCenter of Wisconsin (BCW) on a cli-
                                                                                                                                                                      cines and Health Products (ANSM) tested medical
vironmental, consumer and human health protecti-          bloodbag.eu) was a Life+ collaborative initiati-     nical trial evaluating a new plasticiser for blood
                                                                                                                                                                      devices on the French market, targeting 3 thera-
on through preventive decision-making in the case         ve between industry and the healthcare sector        bags. The aim of the trial is to evaluate the
                                                                                                                                                                      peutic areas in which PVC devices were presented
of risk. Nevertheless, the decision whether or not        that aimed to demonstrate that it is possible        stability of red blood cells in di-2-ethylhexyl te-
                                                                                                                                                                      as DEHP-free: haemodialysis, enteral feeding and
to apply the precautionary principle appears to be        to produce a blood bag without using PVC.            rephthalate (DEHT) plasticised containers com-
                                                                                                                                                                      infusion.77 During market surveillance ANSM obser-
poorly defined, with ambiguities inherent in deter-       The project, which was completed in 2017, has        pared with standard di-2-ethylhexyl phthalate
                                                                                                                                                                      ved that a large number (around 70%) of these de-
mining what level of uncertainty and significance of      shown that it is possible to produce a comple-       (DEHP) plasticised containers. The trial expan-
                                                                                                                                                                      vices in which DEHP was not added as plasticiser,
hazard justifies invoking it.72 Decision makers prefer    tely PVC-free set of four bags, which can store      ded upon the use of DEHT as an alternative to
                                                                                                                                                                      actually contained residual quantities of DEHP, with
to wait until overwhelming scientific evidence is gat-    red blood cells and fulfil the requirement spe-      DEHP for bags to store red blood cells in AS-1
                                                                                                                                                                      however, concentrations lower than 1,000 ppm
hered, often taking a long time to achieve, and po-       cifications including a gap analysis for CE-mar-     and PAGGSM preservative solutions. The trial
                                                                                                                                                                      (0.1%) being observed for most of them.
tentially delaying action to a point where risks and      king.73                                              concluded that DEHT, a non-phthalate gene-
effects cannot be undone.                                                                                      ral-purpose plasticizer, is a viable alternative
                                                          The majority of Swedish healthcare providers
                                                                                                               to DEHP. Although structurally and functional-
On the European market, several manufacturers             and other organisations, including Health                                                                   Non-Governmental Initiatives
                                                                                                               ly similar to DEHP, DEHT (or Eastman 168 SG)
offer products where phthalates/PVC or BPA have           Care Without Harm Europe, supported this
                                                                                                               is metabolically distinct with a comprehensive         The Safer Medical Devices Database by
been replaced by alternative materials or substan-        Initiative, and Karolinska University Hospital
                                                                                                               and benign toxicology profile.74                       HCWH Europe
ces. In the case of the phthalates, phthalate-free or     is now working towards a PVC-free blood pro-
PVC-free medical devices are available for nearly all     cessing and storage system. Their objective is       “PVC blood bags without phthalates of concern
                                                                                                               are just around the corner” 75                         One of the issues that hospitals face when start-
product categories except blood bags (see Box 8).         to identify a partner with the ability to launch
                                                                                                                                                                      ing a phase-out programme for phthalates or BPA
Many hospitals have already made considerable             PVC-free blood bags on the European market.
                                                                                                                                                                      is knowing what alternatives are available and the
progress, having adopted phase-out policies and           Demonstrating widespread demand is critical
                                                                                                                                                                      impact and effectiveness of the alternative. Enga-
committing to using products that are less harmful        to achieving that goal and other European he-
                                                                                                                                                                      gement and communication with manufacturers is
                                                          althcare providers are invited to show support
for patients. However, most of these initiatives are
                                                          for this initiative by signing a Letter of Intent,
                                                                                                               Governmental Initiatives                               therefore essential. To enable healthcare procurers
only happening due to the commitment of indivi-                                                                                                                       to identify medical devices that do not contain PVC
duals and in spite of a lack of political or regulatory   available here:                                      Three European countries – Denmark, France and         and/or DEHP or BPA, and that are already available
impetus.                                                  (https://www.karolinska.se/en/karolinska-univer-     Germany – have taken legislative steps to reduce       on the European market, HCWH Europe launched
In a project for the European Commission’s Direc-         sity-hospital/about-karolinska/environment-and-      the use of phthalates and/or BPA. All three count-     in 2014 an online listing of DEHP-free, PVC-free or
torate General Environment, the Swedish Environ-          sustainability/pvc-free-blood-bag/).                 ries have addressed, to varying degrees, the issue     BPA-free medical products available in the Euro-
mental Management Council developed a set of EU                                                                of DEHP-containing medical devices and provide         pean market – the Safer Medical Devices Database
Green Public Procurement (GPP) criteria with re-                                                               political support to efforts to improve healthcare     (safermedicaldevices.org). Manufacturers, procurers
gards to electrical and electronic medical devices.                                                            in this regard. The Nordic Council of Ministers, the   and anyone else working in the healthcare sector
In 2014, the creation of Green Public Procurement                                                              official inter-governmental body for cooperation in    that would like to provide information about PVC-,
Criteria about electrical and electronic medical de-                                                           the Nordic Region also promotes the Swan Ecola-        DEHP- or BPA-free medical devices, are invited to
vices missed the opportunity to incorporate a crite-                                                           bel, which among other product categories also in-     do so.
rion on phasing out BPA due to insufficient scienti-                                                           cludes certain healthcare products.
fic evidence and supply chain transparency. Given                                                              As all cases were described in the previous edition
                                                                                                                                                                      The Swedish Substitution List by the
the growing amount of data and new tools available                                                             of Non-toxic Healthcare report76, and only new in-
                                                                                                                                                                      Substitution group on chemicals
to track the presence of substances, updating this                                                             formation has been included in 2019 edition.
policy tool would better support sustainable procu-                                                            Since 1 July 2015 tubing/pipes containing DEHP         The Swedish regions and counties and the Swedish
rement strategies aimed at phasing out hazardous                                                               have been banned for use in paediatric, neonatal,      Environmental Management Council, through the
chemicals.

16   NON-TOXIC HEALTHCARE - SECOND EDITION (2019)                                                                                                                                  NON-TOXIC HEALTHCARE - SECOND EDITION (2019)   17
NON-TOXIC HEALTH CARE: SECOND EDITION (2019) Alternatives to Hazardous Chemicals in Medical Devices: Phthalates and Bisphenol A - Health Care ...
CHAPTER 2

national Substitution Group on chemicals, maintain     The ChemSec Marketplace                                    Alternatives to phthalates
and regularly update a Substitution List for hazar-
dous substances in the healthcare sector, available    The Marketplace (https://marketplace.chemsec.org/)         Alternative substances for replacing phthalates          European Pharmacopoeia since 2018. Today, ot-
online.78 The Substitution List compiles information   is a business to business website where buyers and         exist for a number of products, including the ma-        her plasticisers such as Di-isononyl cyclohexanoate
on products available in the Swedish market to help    sellers of alternatives to hazardous chemicals can         jority of applications in medical devices. Several       (DINCH), Tri-2-ethylhexyl trimellitate (TEHTM), and
healthcare procurers make healthier and more in-       interact. Not only does it provide a unique market         companies already manufacture DEHP-free medi-            Dioctyl Terephthalate (DOTP) are being proposed
formed choices. Products are organised by product      opportunity for producers of safer alternatives, but       cal devices, either by using PVC plasticisers other      in medical applications, such as medical tubing and
category (use), and possible alternatives of the ha-   also a one-stop shop for downstream user compa-            than DEHP or by avoiding the use of PVC material         blood bags.
zardous substances are listed for each product, in-    nies looking to substitute hazardous chemicals in          altogether.15                                            Tables summarising the applications, advantages,
cluding at least one supplier.                         their products.
                                                                                                                  A survey of the Denmark medical industry showed          disadvantages, toxicity and main knowledge gaps
                                                                                                                  that in 2014, 95% of the manufacturers still used        relating to known alternative plasticisers to phtha-
The Substitution Portal by Kooperations-               Chemicals substitution by INERIS                           DEHP.81 However, 60% of the companies had also           lates or known alternative polymers to PVC were in-
stelle Hamburg IFE GmbH and partners                                                                              products that do not contain phthalates, and 80%         cluded in the previous edition of Non-toxic Health-
                                                       This website (https://substitution.ineris.fr/en), set up   of those using phthalates believed that substitution     care report.76 These have been moved to the Safer
The Substitution Support Portal – SUBSPORT (http://    by the French National Institute for Industrial En-        should not be problematic over a period of 3-5 ye-       Medical Devices Database (safermedicaldevices.org)
www.subsport.eu) - is a multi-lingual collaborative    vironment and Risks (INERIS) provides support to           ars.81                                                   with the intention of keeping them updated as and
project coordinated by Kooperationsstelle Ham-         economic operators engaged in a substitution ap-                                                                    when appropriate evidence becomes available.
                                                                                                                  No clinical studies have systematically compared
burg IFE GmbH (a consultancy based in Germany),        proach in order to promote the dissemination and
                                                                                                                  the health outcomes of different substances used         A concern that has been raised by a study from
the International Chemical Secretariat – ChemSec       sharing of information. The website currently offers
                                                                                                                  in medical devices, particularly comparing DEHP          Genay et al. (2011).84 and by the French National
(a non-profit organisation based in Sweden), Gront-    information provided by companies on the alterna-
                                                                                                                  and other phthalates with alternatives. Nonethe-         Agency for the Safety of Medicines and Health Pro-
mij (a consultancy based in Denmark) and the Insti-    tives available for three families of substances: bis-
                                                                                                                  less, a number of studies from manufacturers,            ducts77 is that not all DEHP-free devices are in prac-
tuto Sindical de Trabajo, Ambiente y Salud - ISTAS     phenols, phthalates and alkylphenol ethoxylates.
                                                                                                                  regulatory agencies, researchers and NGOs have           tice DEHP-free, as DEHP was present in small quan-
(a technical body of one of the Spanish workers        They are illustrated by concrete applications and
                                                                                                                  looked into alternatives for phthalates or PVC in        tities (below 0.1% by weight). These results point to
unions). The project aims to provide useful informa-   include medical devices.
                                                                                                                  medical devices.19 82 83                                 the necessity for manufacturers to verify the purity
tion on substitution and provide resources to tho-
                                                                                                                  In 2014, the Danish Environmental Protection             of raw materials for all plastics used in the compo-
se interested in substituting hazardous chemicals
                                                                                                                  Agency published a report looking at alternative         sition of the various parts of a medical device and
in products. The Case Story database in the portal
                                                                                                                  plasticisers in medical devices to DEHP, BBP, DBP        not just PVC.
includes the assessment of alternative substances
for ten substances or groups of substances of high                                                                and DIBP. The overall purpose of the report was to
concern – including BPA – plus several case studies                                                               come up with a list of alternatives to help guide ma-
from hospitals.                                                                                                   nufacturers of medical devices to substitute these
                                                                                                                  plasticisers.14 The report screened available infor-
                                                                                                                  mation existing in the REACH registration dossiers
The GreenScreen® Chemicals Alternative                                                                            for a list of substances and found that the values of
Assessment and the Plastics Scorecard by                                                                          the “no effect level” (DNEL) for the general popula-
the Clean Production Action                                                                                       tion were all higher in comparison with DEHP, mea-
                                                                                                                  ning these substances would in principle be safer
The GreenScreen® for Safer Chemicals79, developed
                                                                                                                  than DEHP.14 In the Plastics Scorecard: Evaluating
by the non-profit organisation Clean Production Ac-
                                                                                                                  the Chemical Footprint of Plastics report, the plastic
tion80, employs an open, transparent methodology
                                                                                                                  footprint of polyolefin and PVC in IV bags was com-
to perform chemical hazard assessment. A wide
                                                                                                                  pared.83 The results of the comparison showed that
range of professionals, governmental and non-go-
                                                                                                                  the substitution of PVC bags by polyolefin-based
vernmental bodies and manufacturers use it to
                                                                                                                  polymers greatly reduced the chemical footprint of
assess the hazard of chemicals and their potential
                                                                                                                  the products.
effect on human health and the environment. The
goal is to push for the substitution of hazardous                                                                 The plasticisers industry has been investing and
chemicals by safer alternatives.                                                                                  developing alternatives to DEHP in medical devi-
                                                                                                                  ces. These alternatives have been included in the

18   NON-TOXIC HEALTHCARE - SECOND EDITION (2019)                                                                                                                                       NON-TOXIC HEALTHCARE - SECOND EDITION (2019)   19
You can also read