Christine Clark, BSc, MSc, PhD, FRPharmS, FCPP(Hon)
Occupational exposure of healthcare personnel to cytostatic agents is an issue of current concern in hospital practice. As gloves represent the first line of protection when handling cytostatic agent the permeability of gloves is a critical issue and current guidelines recommend that personnel preparing cytostatic injections should ‘double-glove’ if desired and change gloves every 30 minutes.
It is tempting to think that gloves are all broadly similar but, in fact, protective gloves are available in a range of different materials, which have different properties and permeability characteristics.
These are important factors to take into account when gloves are purchased. Recent work by Professor Pierre Wallemacq and colleagues at the Université Catholique de Louvain (UCL), Brussels, Belgium, has explored these issues and developed a method for permeability testing that could set a new standard in this field.
Most cytostatic agents are considered to be carcinogenic to humans according to the International Agency for Research on Cancer (IARC) and occupational exposure to cytostatic agents is now recognised to be a risk for healthcare personnel. Reported adverse effects include developmental and reproductive toxicity and, most recently, chromosomal changes typical of treatment-related myelodysplasia.
Pierre Wallemacq is well-placed to undertake this type of work. He is head of the Clinical Chemistry department in the Cliniques Universitaires St Luc, and therefore has overall responsibility for drug level measurement in addition to the routine clinical chemistry investigations. He is also Professor at the Université Catholique de Louvain, where he teaches toxicology, clinical pharmacokinetics and clinical biochemistry. His research is focused on the pharmacology of drugs used to prevent organ rejection and he supervises PhD studies in this field. His interest in the permeability of gloves to cytostatic agents was sparked when he was approached by the husband of one of his colleagues – a man who worked for a glove manufacturer and who was looking for permeability-testing expertise. Given that he had the tools, the knowledge about the drugs and an understanding of the way in which the product was used, it was a natural partnership, Professor Walllemacq says.
It is important to assess the permeability of glove material to cytostatic agents in order to protect all the healthcare professionals – that is nurses, doctors and pharmacists – who handle them. “Even with limited exposure a small amount of a cytostatic agent could pass through the skin and potentially be sufficient to have a carcinogenic effect. Although the drugs are used to kill tumour cells they could also cause mutations in normal cells”, says Professor Wallemacq. The issue here is that patients receive acute treatment in wellcontrolled situations but healthcare staff can be exposed to very small amounts of cytostatic agents over long periods, and this could put them at risk of mutations, some of which could have harmful consequences.
The factors that influence permeation rates of drugs through glove materials include:
- The physicochemical properties of the drug, in particular the hydrophobicity; the more hydrophobic the drug, generally, the more easily it will permeate the glove material
- Molecular weight; high molecular weight drugs permeate glove material less easily
- The thickness of the glove material
- The type of material from which the gloves are made – this can be natural rubber latex, vinyl, nitrile or neoprene. Vinyl is most permeable; nitrile, neoprene and natural rubber latex are least permeable
- Temperature; higher temperatures increase permeation
- Duration of exposure
- Drug concentration
- Alcohol; exposure to alcohol can affect the chemical structure of the surface of glove material and increase permeability.
Existing methods for permeability testing of glove materials were static – they involved exposing the glove material to fixed drug concentrations for a specified time and at a specified temperature. “Our purpose was to simulate the real-life situation, where gloves are subject to friction, rubbing and stretching – so we designed a system for dynamic measurement of permeability”, Professor Wallemacq says. He and his team designed a device that could provide standardised dynamic conditions for permeability testing.
Whereas previous test methods had put a known concentration of drug on the exterior surface of the glove and measured the amount that permeated the material after a given time, the new device also incorporated a mechanical stretching procedure to mimic the stretching that would occur in normal use. In each case the results are expressed as nanograms per cm2 per minute.
There were also other differences, Professor Wallemacq points out. For example, testing can be performed at 25°C, 37°C or 43°C. These temperatures are relevant because some types of colorectal surgery involve direct (intraperitoneal) infusion of oxaliplatin at 43°C (hyperthermic intraperitoneal chemotherapy, HIPEC). This approach delivers high peritoneal and tumour concentrations of the drug with limited systemic absorption. It is much more effective than oral or intravenous administration. However, the surgeon’s (gloved) hands can also be exposed to the drug solution, and therefore testing of glove permeability at this temperature is important, he explains.
Another aspect of the new assessment method is pre-treatment of the glove material with alcohol. Most practitioners will use an alcohol-based product at some stage in an aseptic procedure, usually for hard-surface disinfection or for skin sanitisation. Alcohol can denature the external layer of glove material and this could make it more permeable to cytostatic agents, says Professor Wallemacq. Thus, incorporating this step into the test process makes the conditions particularly stringent – but realistic.
In one study 13 different gloves, made from natural rubber latex, vinyl, nitrile and neoprene, were tested with 13 cytostatic agents.1 The results showed that vinyl gloves were the most permeable – after 15 minutes four of six test drugs had permeation rates greater than 10ng/(cm2.min).
In general, gloves made from the other three materials presented a more robust barrier. All materials showed “low but significant permeability” to at least one drug after 60 minutes. Different gloves made of the same material showed different permeabilities. Liposolubility of the drugs used also appeared to play an important role; for example, carmustine (highly liposoluble) permeated the widest variety of materials.
What this means in practice, according to Professor Wallemacq, is that it is critically important to know how gloves perform when making purchasing decisions – especially when a hospital is buying gloves to protect its personnel. “One glove is not necessarily the same as any other glove”, he emphasises. Moreover, these findings could be relevant to a number of other products that can be hazardous to personnel when exposure occurs on a continuous basis. Examples include antiviral agents, such as ganciclovir, which can penetrate the skin, and a number of dyes and other products that are used in molecular biology.
Finally, there are still unanswered questions in this field, Professor Wallemacq says. “We need a better understanding of the ideal frequency of glove changes – the current recommendations are not evidencebased. It could also be important to test the permeation of other non-drug chemicals through gloves.”
Professor Wallemacq concludes that now could be the time for a consensus view on a new standard for the permeability of gloves. “We have much more sensitive analytical methods than those that were available ten years ago and we can detect very small quantities of substances so we should probably demand a more rigorous standard”, he says. The method of glove permeation testing designed and developed by Professor Wallemacq has been adopted by glove manufacturers, Ansell as the Ansell cytostatic permeation programme (ACPP).
1. Wallemacq PE, Capron A, Vanbinst R, Boeckmans E, Gillard J, Favier B. Permeability of 13 different gloves to 13 cytotoxic agents under controlled dynamic conditions. Am J Health-Syst Pharm 2006; 63: 547-556