Jin Yoshida

Use of a Closed System Device to Reduce Occupational Contamination and Exposure to Antineoplastic Drugs in the Hospital Work Environment

OBJECTIVES The aim of the preset study was to evaluate the applicability of a closed system device to protect against occupational contamination and exposure to antineoplastic drugs in the work environment of a hospital. METHODS We compared the contamination by and exposure to cyclophosphamide (CPA) between a conventional mixing method and a mixing method using a closed system device. Wipe samples in the preparation room, gloves samples and 24-h urine samples of pharmacists preparing antineoplastic drugs were collected. Working surfaces inside the biological safety cabinet (BSC), front side of the air grilles of the BSC, stainless steel trays, working table and floor were wiped. At first, sample collection was done on 5 days over an interval of 2 weeks using the conventional mixing method. After 2 weeks training for using the closed system device, sample collection was done 5 days over an interval of 2 weeks using the closed system device. RESULTS When pharmacists prepared antineoplastic drugs by the conventional method, CPA was detected from all wipe samples, and the mean and median concentrations of CPA were 1.0 and 0.16 ng cm(-2), respectively (range was from 0.0095 to 27 ng cm(-2)). When pharmacists prepared antineoplastic drugs with a closed system device, CPA was detected from 75% of the wipe samples at mean and median concentrations of 0.18 and 0.0013 ng cm(-2), respectively (the range was from lower than detection limit to 4.4 ng cm(-2)). Using the closed system device significantly reduced the surface contamination of CPA for all wipe sampling points in the preparation room (Mann-Whitneys U-test). The range of CPA of glove samples used in the conventional method and closed system device ranged from lower than detection limit to 3200 ng per glove-pair and from lower than detection limit to 740 ng per glove-pair, respectively. Using the closed system device significantly reduced the gloves contamination of CPA (Mann-Whitneys U-test). The range of urinary CPA of six pharmacists preparing the antineoplastic drugs with the conventional method and closed system device ranged from lower than detection limit to 170 ng day(-1) and from lower than detection limit to 15 ng day(-1), respectively. Using the closed system device significantly reduced the amount of urinary CPA in pharmacists preparing the antineoplastic drugs (Wilcoxons signed ranks test). CONCLUSIONS We concluded that a closed system device can reduce occupational contamination and exposure to antineoplastic drugs in the hospital work environment.

Association between occupational exposure levels of antineoplastic drugs and work environment in five hospitals in Japan

Purpose. The aim of the present study was to evaluate the measurement of contamination by antineoplastic drugs for safer handling of such drugs by medical workers. We investigated the relationship between the contamination level of antineoplastic drugs and the conditions of their handling. Methods. Air samples and wipe samples were collected from equipment in the preparation rooms of five hospitals (hospitals A—E). These samples were subjected to measurement of the amounts of cyclophosphamide (CPA), fluorouracil (5FU), gemcitabine (GEM), and platinum-containing drugs (Pt). Twenty-four-hour urine samples were collected from the pharmacists who handled or audited, the antineoplastic drugs were analyzed for CPA and Pt. Results. Pt was detected from air samples inside BSC in hospital B. Antineoplastic drugs were detected from wipe samples of the BSC in hospitals A, B, D, and E and of other equipment in the preparation rooms in hospitals A, B, C, and D. Cyclophosphamide and 5FU were detected from wipe samples of the air-conditioner filter in hospital A, and CPA was detected from that in hospital D. Cyclophosphamide was detected from urine samples of workers in hospitals B, D, and E. Conclusion. The contamination level of antineoplastic drugs was suggested to be related with the amount of drugs handled, cleaning methods of the equipment, and the skill level of the technique of maintaining negative pressure inside a vial. In order to reduce the contamination and exposure to antineoplastic drugs in the hospital work environment very close to zero, comprehensive safety precautions, including adequate mixing and cleaning methods was required in addition to BSC and closed system device.

Genotoxic Risks to Nurses from Contamination of the Work Environment with Antineoplastic Drugs in Japan

Genotoxic Risks to Nurses from Contamination of the Work Environment with Antineoplastic Drugs in Japan: Jin Yoshida, et al. Department of Environmental Health, Osaka Prefectural Institute of Public Health—The aims of the present study were to clarify the work environment contamination by antineoplastic drugs in a hospital ward and to assess the genotoxic risks to nurses who routinely handle antineoplastic drugs in Japan. The exposed group consisted of 19 female nurses who routinely handled antineoplastic drugs. The control group consisted of 18 female nurses who did not handle antineoplastic drugs in the same hospital as the exposed group. The genotoxicity of the 19 antineoplastic drugs used in the hospital ward and 8 wipe samples of the workbench after handling of antineoplastic drugs were measured using the umu assay. Lymphocyte DNA damage (tail length) was measured with alkaline methods of the single cell gel electrophoresis assay (comet assay). Of the 19 antineoplastic drugs, dacarbazine, bleomycin, daunorubicin, doxorubicin, pirarubicin, carboplatin, cisplatin and etoposide induced genotoxicity. Of the 8 sampling d, the umu activity of the wipe sample was positive on 3 d. Contamination of the workbench was found when the nurses handled more drugs than on other days. The medians of the tail length in the comet assay were 8.5 and 5.1 μm, respectively, for the exposed and control groups, with a significant difference (p=0.004 by Mann‐Whitneys U‐test). In the present study, the nurses of the exposed group were considered to have been exposed to antineoplastic drugs and lymphocyte DNA damage of the exposed group was suggested to be induced by antineoplastic drugs.

Association between Occupational Exposure and Control Measures for Antineoplastic Drugs in a Pharmacy of a Hospital

OBJECTIVES To investigate the association between occupational contamination and exposure levels to antineoplastic drugs and the application of control measures in a hospital work environment. METHODS Wipe samples of equipments were collected at a hospital in Osaka Prefecture, Japan, from 2007 to 2011. These samples were subjected to measurements of cyclophosphamide (CP), gemcitabine (GEM), platinum-containing drugs (Pt), and fluorouracil (5FU). Additionally, 24-h urine samples were collected from pharmacists who handled antineoplastic drugs, which were analyzed for CP and alpha-fluoro-beta-alanine (AFBA). The application of control measures was scored according to a checklist, which consisted of the following five items: safety equipment and maintenance, training and documentation, devices for safe handling, personal protective equipment, and emergency care. The aim was to obtain a score of 80%. RESULTS The median CP, GEM, and 5FU concentrations of all wipe samples were significantly lower during the period when the mean score was >80% (attainment period) versus when the mean score was ≤80% (nonattainment period; all P < 0.001, Mann-Whitneys U-test). Additionally, the median urinary CP and AFBA concentrations of pharmacists during the attainment period tended to be lower than that of those during the nonattainment period (P = 0.061 and 0.061, respectively, using Mann-Whitneys U-test). CONCLUSIONS Contamination and levels of exposure to antineoplastic drugs decreased with a score higher than 80%. The scores of the items on the checklist appeared to adequately reflect the condition of the control measures, as increases in all five items were associated with reductions in the contamination by and levels of exposure to all drugs.

Simultaneous analytical method for urinary metabolites of organophosphorus compounds and moth repellents in general population.

An analytical method was developed for simultaneous measurement of urinary metabolites in the general population exposed to organophosphorus compounds (insecticides, flame retardants and plasticizers) and moth repellents used in Japanese households. Fifteen metabolites, dimethylphosphate, dimethylthiophosphate, diethylphosphate, diethylthiophosphate, di-n-butylphosphate, diphenylphosphate, bis(2-ethylhexyl)phosphate, 2-isopropyl-6-methyl-4-pyrimidinol, 3,5,6-trichloro-2-pyridinol, 3-methyl-4-(methylthio)phenol, 3-methyl-4-nitrophenol, 2,4-dichlorophenol, 2,5-dichlorophenol, 1-naphthol and 2-naphthol, were extracted from hydrolyzed urine by using a sorbent (hydroxylated polystyrene-divinylbenzene copolymers), and then desorbed with methylacetate and acetonitrile, concentrated, and after transformation to their tert-butyldimethylsilyl derivatives, analyzed by gas chromatography/mass spectrometry in the electron impact ionization mode. They could be determined accurately and precisely (quantification limits: 0.8-4 μg/l). The collected urine samples could be stored for up to 1 month at -20°C in a freezer.

Actual conditions of the mixing of antineoplastic drugs for injection in hospitals in Osaka Prefecture, Japan.

Actual Conditions of the Mixing of Antineoplastic Drugs for Injection in Hospitals in Osaka Prefecture, Japan: Jin Yoshida, et al. Department of Environmental Health, Osaka Prefectural Institute of Public Health—We conducted a questionnaire survey in order to grasp the actual conditions under which antineoplastic drugs are mixed for injection in hospitals. Questionnaires were sent to all 155 hospitals with 100 or more beds for general patients in Osaka Prefecture, Japan. The response rate was 69.0%. Mixing of antineoplastic drugs was done in 81.3% of the hospitals. The questionnaire was answered by doctors in 17.2% of the hospitals with antineoplastic drugs, nurses in 11.5%, and pharmacists in 70.1%. Mixing of antineoplastic drugs was done by doctors in 58.6% of the hospitals, nurses in 44.8%, and pharmacists in 63.2% (multiple answers). Occupational exposure to antineoplastic drugs was recognized in 97.7% of the hospitals. The mean frequency of the mixing operation was 8.8 d per month per worker. The mean number of antineoplastic drugs handled was 7.4 types. Guidelines for the safe handling of antineoplastic drugs were used in 52.8% of the hospitals and a biological safety cabinet was available in 57.4%. Gloves, mask, gown and goggles were used in 82.7, 69.0, 62.1 and 36.8% of the hospitals, respectively, but no personal protective equipment was used in 10.1%. The safety precautions of the hospitals in which the number of beds was small tended to be fewer than those of the hospitals in which the number of beds was large. Used vials and ampoules were disposed of as clinical, infectious or exclusive antineoplastic drug waste by 74.7% of the hospitals. Safety measures for handling the excrement of patients treated with antineoplastic drugs were performed in 8.0% of the hospitals. In 43.7% of the hospitals, the responders had experienced accidents during antineoplastic drug preparation, such as drugs adhering to hands or eyes, drug leakage, accidental injection and cutting by ampoules. Because of the adverse effects of antineoplastic drugs, all hospitals in which the healthcare workers handle them should promote safety precautions.

Effects of Dioxin on Metabolism of Estrogens in Waste Incinerator Workers

The authors measured the concentrations of serum dioxins and urinary estrogen metabolites in 57 male waste incinerator workers to determine whether dioxin influenced the metabolism of estrogens. Concentrations of serum dioxin levels and urinary estrogen metabolites, such as estrone, 17α-estradiol, 2-hydroxyestrone, 2-methoxyestrone, 2-hydroxyestradiol, 2-methoxyestradiol, 4-hydroxyestrone, 4-hydroxyestradiol, 4-methoxyestradiol, 16-hydroxyestrone, and estriol from the workers were measured. An analysis of covariance showed that mean estriol concentrations, adjusted for confounding factors among 3 serum dioxin levels, indicated a progressive increase with increasing serum dioxin level: 1.30, 1.41, and 2.02 nmol/mol creatinine at <30.3, 30.3-39.7, and >39.7 pg toxicity equivalent quantity/g lipid, respectively (F = 3.56, p = .036). This study showed that dioxin acts to metabolize estrogens to 16-hydroxyestrogens rather than to 2-or 4-hydroxyestrogens.