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A study protocol for the evaluation of occupational mutagenic/carcinogenic risks in subjects exposed to antineoplastic drugs: a multicentric project

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BMC Public Health. 2011; 11:195 (ISSN: 1471-2458)
Moretti M; Bonfiglioli R; Feretti D; Pavanello S; Mussi F; Grollino MG; Villarini M; Barbieri A; Ceretti E; Carrieri M; Buschini A; Appolloni M; Dominici L; Sabatini L; Gelatti U; Bartolucci GB; Poli P; Stronati L; Mastrangelo G; Monarca S Department of Medical-Surgical Specialties and Public Health, University of Perugia, Via del Giochetto, 06122 Perugia, Italy. BACKGROUND: Some industrial hygiene studies have assessed occupational exposure to antineoplastic drugs; other epidemiological investigations have detected various toxicological effects in exposure groups labeled with the job title. In no research has the same population been studied both environmentally and epidemiologically. The protocol of the epidemiological study presented here uses an integrated environmental and biological monitoring approach. The aim is to assess in hospital nurses preparing and/or administering therapy to cancer patients the current level of occupational exposure to antineoplastic drugs, DNA and chromosome damage as cancer predictive effects, and the association between the two. METHODS/DESIGN: About 80 healthy non-smoking female nurses, who job it is to prepare or handle antineoplastic drugs, and a reference group of about 80 healthy non-smoking female nurses not occupationally exposed to chemicals will be examined simultaneously in a cross-sectional study. All the workers will be recruited from five hospitals in northern and central Italy after their informed consent has been obtained.Evaluation of surface contamination and dermal exposure to antineoplastic drugs will be assessed by determining cyclophosphamide on selected surfaces (wipes) and on the exposed nurses' clothes (pads). The concentration of unmetabolized cyclophosphamide as a biomarker of internal dose will be measured in end-shift urine samples from exposed nurses. Biomarkers of effect and susceptibility will be assessed in exposed and unexposed nurses: urinary concentration of 8-hydroxy-2-deoxyguanosine; DNA damage detected using the single-cell microgel electrophoresis (comet) assay in peripheral white blood cells; micronuclei and chromosome aberrations in peripheral blood lymphocytes. Genetic polymorphisms for enzymes involved in metabolic detoxification (i.e. glutathione S-transferases) will also be analysed.Using standardized questionnaires, occupational exposure will be determined in exposed nurses only, whereas potential confounders (medicine consumption, lifestyle habits, diet and other non-occupational exposures) will be assessed in both groups of hospital workers.Statistical analysis will be performed to ascertain the association between occupational exposure to antineoplastic drugs and biomarkers of DNA and chromosome damage, after taking into account the effects of individual genetic susceptibility, and the presence of confounding exposures. DISCUSSION: The findings of the study will be useful in updating prevention procedures for handling antineoplastic drugs.

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CAS Registry / EC Numbers 0 (8-hydroxy-2'deoxyguanosine) 0 (Antineoplastic Agents) 0 (Biological Markers) 50-18-0 (Cyclophosphamide) 961-07-9 (Deoxyguanosine)

DNA Damage Nursing Staff, Hospital

Antineoplastic Agents [toxicity]  Biological Markers [urine] Chromosome Aberrations [chemically  induced]  Cross-Sectional Studies  Cyclophosphamide [analysis]  Deoxyguanosine [analogs & derivatives] [urine] Environmental Monitoring [methods] Female Humans Italy Neoplasms [chemically induced] Occupational Diseases [chemically induced] Occupational Exposure [analysis] Oncologic Nursing Risk

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PreMedline Identifier: 21450074

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Helsinki. 5. Anderson D Finnish Institute of Occupational Health. Major Subject Heading(s) Minor Subject Heading(s) CAS Registry / EC Numbers .g. and. programs for education and training for safe handling of anticancer drugs are crucial. pharmacies and drug manufacturing companies of most developed countries. a database of the U. Murata K Department of Basic Nursing.. 355(1-2):253-61 (ISSN: 0027-5107) Sorsa M. and 193 general hospitals with over 300 beds and at least five or more clinics in Japan. specific analytical methods).). 39% of the nurses took protective countermeasures against anticancer drugs. Therefore. (1988) Mutation Res. persons employed in the manufacture.. However. not doctors or pharmacists. Akita University. 52(8):727-35 (ISSN: 0546-1766) Ishii N. 36. (1994b) Arch. 57). Major Subject Heading(s)     Minor Subject Heading(s) CAS Registry / EC Numbers 0 (Antineoplastic Agents) Antineoplastic Agents  Health Personnel  Occupational Exposure  PreMedline Identifier: 8781586 Drug Industry  Environmental Monitoring [methods] Humans From MEDLINE®/PubMed®. [Safety awareness of anticancer drug handling among Japanese nurses]. Awareness of adverse effects was significantly related with precaution in anticancer drug handling. the use of biological exposure markers is appropriate for the monitoring of such exposure patterns. 13 cancer-special hospitals. Another study showed surface wipe samples with measurable cyclophosphamide even away from the handling site (McDevitt et al. but this might be an overestimate because of the sampling bias. urinary mutagenicity) or specific for a given compound (immunological methods for DNA adducts. mutagenic and teratogenic in experimental animals and in in vitro test systems. 1996. Many anticancer agents have been shown to be carcinogenic. Although 82% of the nurses were concerned about the potential health effects of occupational exposure. preparation and administration of the drugs to patients and in nursing patients may also be exposed. Epidemiological data on the association of second neoplasms with a specific chemotherapy treatment is available on some 30 agents. Env. for which 95% of the nurses stated a desire for special education and training. The exposure is typically to mixed compounds over long-term and to low exposure levels with accidental peaks. A total of 571 female nurses responded to the questionnaire. Sasaki M. Occup. Med. Since only small numbers of nurses take sufficient safety precaution. cytogenetic damage. Regarding safety. since the introduction of various general handling guidelines.S. 1987 and 1990). is now good practice in hospitals. Mutat Res. toxicokinetics of the agent(s) to be assessed and individual working practices should be carefully considered in any exposure assessment studies using human body fluid samples. 79. Also accidental spillage is never completely avoidable (Sorsa et al. Safe handling of anticancer drugs. Dakeishi M. RESULTS: About 40% of the nurses were not at all aware of the potential adverse effects of occupational exposure to anticancer drugs. Sessink et al. Nihon Koshu Eisei Zasshi. Finland. CONCLUSIONS: Approximately 60% of Japanese nurses are aware of the risk of occupational exposure to anticancer drugs.. National Library of Medicine. in most cases. (1994a) J. Studies have revealed minor amounts of cyclophosphamide in the urine of pharmacy technicians and nurses handling the drug even when taking special safety precautions (Sessink et al. and in the case of 10 compounds the overall evidence on human carcinogenicity has been evaluated to be conclusive (Group 1: IARC. Med.Monitoring of occupational exposure to cytostatic anticancer agents. Careless handling of cancer chemotherapeutic agents may lead to exposure of the personnel in amounts detectable with chemical or biological methods in the body fluids or cell samples of the subjects. Eighty-eight percent of the nurses prepared anticancer drugs in the hospital wards. The primary source of human exposure to anticancer drugs is from their use in therapy of cancer. transported and administered such drugs to cancer patients. 15% paid special attention to the handling environment. Occup. The biological markers/methods for exposure assessment are either non-specific (e. 465-479). only 7% took countermeasures with body fluids or linen handling of cancer patients. as well as their associations. 75% or over did not know whether the exposure might affect their future health or progeny. 10% had guidelines for the handling of anticancer drugs. 204. A properly performed study should also include dissemination of information to the workers to create a psychologically positive atmosphere for this important work. These studies strongly implicate the importance of skin absorption as an exposure route. 49. The potential confounders (smoking etc. 165).. Health. School of Health Sciences. point mutations or 32P-postlabelling adducts in peripheral blood lymphocytes. METHODS: A self-rating questionnaire was mailed to 939 nurses in 107 university hospitals. nurses. Environmental monitoring on indicator cytostatics should be combined into studies designed to identify potential occupational exposure situations to anticancer agents. 2005. (1993) J. OBJECTIVES: The purpose of this study was to investigate Japanese nurses' awareness of the adverse effects of occupational exposure to anticancer drugs and safe handling.

Murata K Department of Basic Nursing. A total of 571 female nurses responded to the questionnaire. 52(8):727-35 (ISSN: 0546-1766) Ishii N. and. transported and administered such drugs to cancer patients. 15% paid special attention to the handling environment. Sasaki M. nurses. Since only small numbers of nurses take sufficient safety precaution. Eighty-eight percent of the nurses prepared anticancer drugs in the hospital wards. 39% of the nurses took protective countermeasures against anticancer drugs. National Library of Medicine. CONCLUSIONS: Approximately 60% of Japanese nurses are aware of the risk of occupational exposure to anticancer drugs. School of Health Sciences. as well as their associations. 13 cancer-special hospitals. .S. 10% had guidelines for the handling of anticancer drugs. in most cases. METHODS: A self-rating questionnaire was mailed to 939 nurses in 107 university hospitals. and 193 general hospitals with over 300 beds and at least five or more clinics in Japan. [Safety awareness of anticancer drug handling among Japanese nurses]. OBJECTIVES: The purpose of this study was to investigate Japanese nurses' awareness of the adverse effects of occupational exposure to anticancer drugs and safe handling. 2005. programs for education and training for safe handling of anticancer drugs are crucial.   Awareness Oncologic Nursing Safety       Adult  0 (Antineoplastic Agents) Antineoplastic Agents [adverse effects] Female Humans Middle Aged Occupational Exposure [adverse effects]  PreMedline Identifier: 16218413 From MEDLINE®/PubMed®. Although 82% of the nurses were concerned about the potential health effects of occupational exposure. Awareness of adverse effects was significantly related with precaution in anticancer drug handling. Regarding safety.S. not doctors or pharmacists. but this might be an overestimate because of the sampling bias. Nihon Koshu Eisei Zasshi. a database of the U. Akita University. 75% or over did not know whether the exposure might affect their future health or progeny. only 7% took countermeasures with body fluids or linen handling of cancer patients. Major Subject Heading(s)    Minor Subject Heading(s) CAS Registry / EC Numbers Awareness Oncologic Nursing Safety       Adult  0 (Antineoplastic Agents) Antineoplastic Agents [adverse effects] Female Humans Middle Aged Occupational Exposure [adverse effects]  PreMedline Identifier: 16218413 From MEDLINE®/PubMed®. Dakeishi M. for which 95% of the nurses stated a desire for special education and training. National Library of Medicine. a database of the U. RESULTS: About 40% of the nurses were not at all aware of the potential adverse effects of occupational exposure to anticancer drugs.