The fate and effects of cytostatic (anticancer or antineoplastic) pharmaceuticals in the environment are largely unknown, but they can contaminate wastewater treatment effluents and consequently aquatic ecosystems. In this paper, we have focused on five cytostatic compounds used in high amounts (cyclophosphamide, cisplatin, 5-fluorouracil, doxorubicin, and etoposide), and we have investigated their ecotoxicity in bacterial Pseudomonas putida growth-inhibition test, algal Pseudokirchneriella subcapitata growth-inhibition test, and Dapnia magna acute immobilization test. Genotoxicity also was assessed with Escherichia coli SOS-chromotest (with and without metabolic activation) and the GreenScreen Assay using yeast S. cerevisiae. All tested compounds showed significant effects in most of the assays with lowest-observed-effect concentrations and concentrations causing 50% effects (EC50s) values ranging within microg/L to mg/L. The most toxic compound was 5-fluorouracil in the assays with P. putida (EC50 = 0.027 mg/L) and P. subcapitata (EC50 = 0.11 mg/L), although cisplatin and doxorubicin were the most toxic to D. magna (EC50 = 0.64 and 2.0 mg/L, respectively). These two chemicals were also the most genotoxic in the SOS-chromotest (minimum genotoxic concentrations [MGC] = 0.07-0.2 mg/L), and 5-fluorouracil was the most genotoxic in the eukaryotic yeast assay (MGC = 0.02 mg/L). Our investigation seems to indicate generally lower risks of acute effects at concentrations expected in the environment. However, some effective concentrations were relatively low and chronic toxicity of cytostatics (and/or their transformation products), as well as specific sources of human pharmaceuticals such as hospital effluents, require research attention.

Wound dressings with silver have been shown to be cytotoxic in vitro. However, the extrapolation of this cytotoxicity to clinical settings is unclear. We applied dressings with various forms of silver on porcine skin ex vivo and investigated silver penetration and DNA damage. We assessed antimicrobial efficacy, cytotoxicity to skin cells, and immune response induced by the dressings. All dressings elevated the DNA damage marker γ-H2AX and the expression of stress-related genes in explanted skin relative to control. This corresponded with the amount of silver in the skin. The dressings reduced viability, induced oxidative stress and DNA damage in skin cells, and induced the production of pro-inflammatory IL-6 by monocytes. The oxidative burst and viability of activated neutrophils decreased. The amount of silver released into the culture medium varied among the dressings and correlated with in vitro toxicity. However, antimicrobial efficiencies did not correlate strongly with the amount of silver released from the dressings. Antimicrobial efficiency and toxicity are driven by the form of silver and the construction of dressings and not only by the silver concentration. The damaging effects of silver dressings in ex vivo skin highlight the importance of thorough in vivo investigation of silver dressing toxicity.

The fate and effects of cytostatic (anticancer or antineoplastic) pharmaceuticals in the environment are largely unknown, but they can contaminate wastewater treatment effluents and consequently aquatic ecosystems. In this paper, we have focused on five cytostatic compounds used in high amounts (cyclophosphamide, cisplatin, 5‐fluorouracil, doxorubicin, and etoposide), and we have investigated their ecotoxicity in bacterial Pseudomonas putida growth‐inhibition test, algal Pseudokirchneriella subcapitata growth‐inhibition test, and Dapnia magna acute immobilization test. Genotoxicity also was assessed with Escherichia coli SOS‐chromotest (with and without metabolic activation) and the GreenScreen Assay using yeast S. cerevisiae. All tested compounds showed significant effects in most of the assays with lowest‐observed‐effect concentrations and concentrations causing 50% effects (EC50s) values ranging within μg/L to mg/L. The most toxic compound was 5‐fluorouracil in the assays with P. putida (EC50 = 0.027 mg/L) and P. subcapitata (EC50 = 0.11 mg/L), although cisplatin and doxorubicin were the most toxic to D. magna (EC50 = 0.64 and 2.0 mg/L, respectively). These two chemicals were also the most genotoxic in the SOS‐chromotest (minimum genotoxic concentrations [MGC] = 0.07–0.2 mg/L), and 5‐fluorouracil was the most genotoxic in the eukaryotic yeast assay (MGC = 0.02 mg/L). Our investigation seems to indicate generally lower risks of acute effects at concentrations expected in the environment. However, some effective concentrations were relatively low and chronic toxicity of cytostatics (and/or their transformation products), as well as specific sources of human pharmaceuticals such as hospital effluents, require research attention.

This study investigates the surface contamination levels of cyclophosphamide and platinum (a marker of platinum-containing drugs) in storage and preparation areas of hospital pharmacies and their relationship to working conditions surveyed by questionnaire. In total, 259 wipe samples were collected in 13 hospital pharmacies over 4 sampling campaigns. After sample extraction with acetate buffer, cyclophosphamide and platinum were determined using high-performance liquid chromatography-tandem mass spectroscopy (HPLC-MS/MS) and inductively coupled plasma mass spectrometry (ICP-MS). Depending on the sampling spot and campaign, median concentrations ranged from <2 to 61 pg/cm(2) and from <0.2 to 6.9 pg/cm(2) for cyclophosphamide and platinum, respectively. Statistical evaluation of monitoring data revealed that the contamination level was significantly influenced by laboratory throughput (expressed as number of chemotherapies prepared per week), personnel expertise (ie, participation of pharmacists with academic education in drug admixture activities), and surface material.

The measures implemented in the outpatient clinic were shown to reduce workplace contamination effectively. Therefore, they can be recommended also for other workplaces where antineoplastic drugs are administered. In contrast, measures implemented in the preparation room, where relatively strict regulations had already been adopted before the study, were less effective. To decrease the actual contamination of the preparation room, other protective measures (e.g. closed-system transfer devices) should be considered.

The main objective of the study was to evaluate the applicability of two solid sorbent media (Anasorb 708 and Strata X), the impinger filled with distilled water and PTFE filters for determination of airborne cyclophosphamide (CP) in the hospital working environment. For this purpose, air contamination of Masaryk Memorial Cancer Institute (Czech Republic) was monitored using the sampling apparatus containing the samplers described above. In addition, the surface contamination was also determined using the wipe sampling technique. During the monitoring, contamination of three different workplaces (storage room, preparation room and outpatient clinic) was studied. Using Strata X solid sorbent tubes, airborne CP was determined in all (n = 5) samples collected at the outpatient clinic over a 5 day monitoring period (concentration range: 0.3-4.3 ng m(-3)). Other samplers (including PTFE filters) did not collect any detectable amount of CP (the limit of detection, LOD ≤ 0.1 ng m(-3)). Negative results detected at filter samples indicate that CP determined at Strata X samples was most probably of gaseous origin. Surface contamination ranged from <2 to 19, <8 to 418 and 133-15,500 pg cm(-2) at the storage room, preparation room and outpatient clinic, respectively. The study showed that evaporation of antineoplastic drugs should not be neglected, albeit the concentrations determined in our study are relatively low. Therefore, proper monitoring of airborne contamination should involve simultaneous sampling of both particle-bonded and gaseous phases. In this way, Strata X sorbent tubes seem to be an effective tool for the sampling of gaseous CP in the indoor air.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.