title: Leukemia from dermal exposure to cyclophosphamide among nurses in The Netherlands: quantitative assessment of the risk.
abstract: Several studies showed that oncology nurses are exposed to antineoplastic drugs via the skin during daily activities. Several antineoplastic drugs (including cyclophosphamide) have been classified as carcinogenic to humans. This study aims to assess the leukemia risk of occupational exposure to cyclophosphamide. Average task frequencies from the population of oncology nurses in the Netherlands and task-based dermal exposure intensities were used to calculate oncology nurses' dermal exposure levels. A dermal absorption model in combination with a physiologically based pharmacokinetic model was used to assess the delivered dose of cyclophosphamide and its active metabolites in the bone marrow. This delivered dose was subsequently related to pharmacodynamic and epidemiological information from a longitudinal study with cyclophosphamide-treated patients to estimate the excess lifetime leukemia risk at age 80 for Dutch oncology nurses after 40 years of exposure to cyclophosphamide. The excess lifetime leukemia risk at age 80 of an exposed oncology nurse after 40 years of dermal exposure to cyclophosphamide was estimated to be 1.04 per million oncology nurses. This risk could potentially increase to a maximum of 154 per million if a nurse performs all cyclophosphamide-related tasks with the maximum frequency (as observed in this population) and is exposed to maximum exposure intensities for each task without using protective gloves for 40 years. This study indicates that the risk of an oncology nurse in a Dutch hospital with an average dermal exposure to cyclophosphamide is well below the maximum tolerable risk of one extra death from cancer per 250 deaths after 40 years of occupational exposure, and that this level is not exceeded in a worst-case scenario.
authors.affiliation: 1. Institute for Risk Assessment Sciences, Utrecht University, PO Box 80178, 3508 TD Utrecht, The Netherlands;
authors.forename: Wouter
authors.initials: W
authors.lastname: Fransman
authors.forename: Hans
authors.initials: H
authors.lastname: Kager
authors.forename: Tim
authors.initials: T
authors.lastname: Meijster
authors.forename: Dick
authors.initials: D
authors.lastname: Heederik
authors.forename: Hans
authors.initials: H
authors.lastname: Kromhout
authors.forename: Lützen
authors.initials: L
authors.lastname: Portengen
authors.forename: Bas J
authors.initials: BJ
authors.lastname: Blaauboer
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects* / Q000032:analysis / Q000493:pharmacokinetics; D003520:Cyclophosphamide / Q000009:adverse effects* / Q000032:analysis / Q000493:pharmacokinetics; D017575:Gloves, Protective; D006801:Humans; D007938:Leukemia / Q000139:chemically induced* / Q000453:epidemiology; D008137:Longitudinal Studies; D008452:Maximum Allowable Concentration; D009426:Netherlands / Q000453:epidemiology; D016273:Occupational Exposure / Q000009:adverse effects* / Q000032:analysis; D009859:Oncology Nursing; D018570:Risk Assessment; D012869:Skin Absorption
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003520:Cyclophosphamide
keywords: antineoplastic drugs; cyclophosphamide; leukemia; nurses; occupational dermal exposure; pharmacokinetic model