Phthalates are a family of compounds used in a vast range of products. The global production and use of phthalates exceed 860 billion kilogrammes per year. Phthalates are classified into two distinct groups (based on molecular weight): 

When exposure to hazardous chemicals in medical devices can be avoided through careful selection of materials, not carrying out such substitution is both unprofessional and undesirable.

1. High molecular weight compound (e.g. di-2-ethylexyl phthalate [DEHP]), which are primarily used as plasticisers in the manufacture of flexible vinyl plastic present in flooring and wall covering as well as medical devices
2. Low molecular weight compounds (e.g. diethyl phthalate, dibutyl phthalate) are used in personal care products such as solvents for perfumes and fixatives for hair spray, and as solvents and plasticisers for cellulose acetate.

Health effects of phthalate exposure

Studies show that women, neonates and young children are at greatest risk of the effects of phthalate exposure. In this section we will focus on the effects of phthalates on children.

Most phthalates are ingestion via food. Some phthalates have been found at higher levels in fatty foods such as dairy products, fish, seafood and oils. Phthalates in a mother’s body can enter her breast milk. Ingestion of that breast milk and infant formula containing phthalates contribute to infant exposure.

Phthalates have been shown to cross the placenta. In a study of cord blood of 84 human babies, Latini et al found that 88% of the new-borns had detectable mean concentration of DEHP of 1.19µg/ml, while babies with monoethylhexyl phthalic acid (MEHP) in their cord blood, showed a significantly lower gestational age (27-42 weeks) in comparison to the MEHP negative infants (37-42 weeks).

Phthalates may also be present in dust, which can be ingested by infants and children through hand-to-mouth activities. Finally, infants and small children can be exposed to phthalates by sucking on toys and objects made with phthalate-containing plastics. Other minor routes of phthalate exposure include inhalation, drinking contaminated water, and absorption through the skin. Once consumed, phthalates are rapidly metabolised in the gut, liver, and blood by esterases and lipases.

Exposure to phthalates has the following health effects on children:

Neurodevelopment

Previous studies have reported inverse associations between maternal prenatal urinary phthalate metabolite concentrations and mental and motor development in pre-schoolers. Researchers at Columbia University (United States) took these studies one step further to evaluated whether these associations persist into school age.

Factor-Litvak et al found that children exposed during pregnancy to elevated levels of phthalates had an IQ score, which was on average, more than six points below children exposed at lower levels.

The past few years have seen an upsurge in the prevalence of children with attention-deficit hyperactivity disorder (ADHD), now described as one of the most ‘common’ neurodevelopmental disorders.

Verstraete et al assessed whether there is a link between circulating DEHP leaching from indwelling medical devices and the development of ADHD in children treated in paediatric intensive care units (PICUs). Follow-up was four years post-PICU stay. The authors found that phthalate exposure could explain up to 50% of ADHD in these post-PICU patients. They also found that these children’s motor skills were impaired.

Child growth and adiposity

Vafeiadi et al evaluated the association between phthalate exposure during gestation and childhood, and offspring obesity and cardiometabolic risk factors. They found that boys, exposed to phthalates had lower body mass index (BMI) z-scores, while girls had higher z-scores.

Each 10-fold increase in DEHP was associated with a change in waist circumference of −2.6cm in boys versus 2.14cm in girls and a change in waist-to-height ratio of −0.01 in boys versus 0.02 in girls.

Phthalate concentrations at age four were negatively associated with systolic and diastolic blood pressure (BP). Monoethyl phthalate was associated with lower systolic BP z-scores at four years, while mono-n-butyl phthalate and monobenzyl phthalate were associated with lower diastolic BP z-scores. A 10-fold increase in mono-isobutyl phthalate was associated with 4.4% higher total cholesterol levels. The researchers concluded that early life phthalate exposure may affect child growth and adiposity in a sex-specific manner and depends on the timing of exposure. They found no link between phthalate exposure and increased CVD risk.

Allergies

Jahreis et al looked at a possible link between prenatal and early postnatal exposures to phthalates and the increasing prevalence of asthma in young children. Using a murine transgenerational asthma model, they demonstrate a direct effect of butyl benzyl phthalate on asthma severity in offspring with persistently increases in airway inflammation in subsequent generations.

According to the authors, their findings provide strong evidence that maternal phthalate exposure increases the risk for allergic airway inflammation in offspring by modulating the expression of genes involved in TH2 differentiation through epigenetic alterations.

Precocious puberty

Precocious puberty can be defined as sex hormone production or exposure occurring earlier than the norms for gender and racial or ethnic background. Harley et al looked at the association of phthalates, parabens and phenols found in personal care products and pubertal timing in girls and boys.

Regarding peripubertal biomarkers, they found earlier breast development, pubic hair development and menarche with methyl paraben, earlier menarche with propyl paraben and later pubic hair development with 2.5-dichlorophenol in girls. In boys, they observed no associations with prenatal urinary biomarker concentrations and only one association with peripubertal concentrations; namely earlier genital development with propyl paraben.

How can we minimise the risk?

Phthalates in the healthcare environment

Phthalates are commonly used as softeners in PVC-based medical devices. Exposure to hazardous chemicals through medical devices can be enteral (digestive tract), parenteral (intravenous), transcutaneous or through inhalation.

Phthalates are used disposable products such as opheresis circuits, blood bags and tubing, extracorporeal membrane oxygenation circuits, drainage and urinary collection bags, catheters, wound draining systems, enteral feeding sets, nasogastric tubes, gloves, a number of intravenous and dialysis therapy products.

They are also used in the packaging of medical products and devices and in a number of patient products such as ID bracelets, bed pans, cold and heat pacts, compression devices and inflatable splints.

In respiratory therapy products, phthalates are used in oxygen masks, endotracheal and tracheostomy tubes, humidifiers, water bags and resuscitator bags. They are also used in durable medical products, in office equipment and in furniture.

In short, phthalates are everywhere!

Exposure to phthalates can be minimised by adopting a precautionary approach and replacing medical devices with phthalate-free devices which can provide the same efficiency. Several manufacturers now offer products where phthalates/PVC has been replaced by alternative materials or substances. In the case of the phthalates, phthalate-free or PVC-free medical devices are available for nearly all product categories.

In 2014, Healthcare without Harm Europe proposed a number of specific recommendations to promote a move towards non-toxic healthcare. These included:

  • Legislation that protect the most vulnerable groups and create the conditions to rapidly reduce or eliminate human exposure to hazardous chemicals in medical devices. This can be done by creating a regulatory framework that requires the phase-out of hazardous chemicals, such as phthalates contained in medical devices, and protects the safety of patients and healthcare workers
  • Standards for pre-market evaluation of medical devices should include more data on chemicals used in medical devices and allow a performance comparison of individual substances
  • The market authorisation process for medical devices needs increased transparency to ensure that approved medical devices are both efficient and safe for patients
  • Sustainable procurement guidelines should provide incentives for the substitution of hazardous chemicals in medical devices eg the European Green Public Procurement policy
  • Labelling requirements for hazardous chemicals in medical devices should be expanded eg indicate hazardous substances in medical devices and develop harmonised environmental criteria for hazardous chemicals in medical devices
  • Funding for research and development of alternative substances and products and for clinical and epidemiological projects that compare the performance of these alternatives should be prioritised.

In Europe and elsewhere many hospitals have already made considerable progress in phasing-out phthalate products and substituting it for ones that are less harmful for patients. Examples include:

  • The Hospital of Southern Jutland (Denmark) started a substitution project in 2005 to replace medical devices containing PVC. The project focused on medical devices coming into contact with patients, primarily neonates and children
  • Karolinska University Hospital (Sweden) has started a substitution programme in 2006. By 2014, they had phased out more than 88% of phthalate-containing products and devices
  • Doctors and nurses at the Paediatrics and Neonatology Department in the Westfriesgasthuis (The Netherlands) have pushed for a procurement policy to phase out PVC medical devices used in these units. The policy covered all product categories used in the department and allows for substitution of a majority of the products (80%-100%). They found that some of the alternatives were cheaper than the PVC-containing ones
  • Neonatal Intensive Care Units of the Vienna Hospitals Association (Austria) also adopted a PVC-free policy in their units. The criteria cover invasive consumables and products that come into contact with the skin of babies.

Procurement practices can contribute to a quicker phase-out of certain hazardous chemicals in medical devices by driving manufacturers to develop alternatives to those chemicals/products and by assessing if the available alternatives are feasible. 

Cost-effectiveness of substitution

Although expense has been identified in the past as a reason for using disposable products, it is now becoming more cost-effective to switch to reusable alternatives, write North and Halten.

In fact, say the authors, substitution can potentially result in a 50% reduction of medical equipment costs. They cite a Californian Hospital (United States) as a case in point. This hospital switched from using blue polypropylene wrap for keeping surgical tools in the operating room sterile to using surgical hard cases for protection, resulting in a R720 000 annual savings.

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Conclusion

Phthalates are widely used in everyday products as well as healthcare devices and consumables. Exposure to phthalates has important health implications. Exposure risk can be minimised by phasing out phthalate-containing devices and consumables and substituting it with safer alternatives. Developing an effecting procurement plan to phase out these harmful devices and consumables can lead to cost savings in the long-term.