[Study for the revision of analytical method for tris (2,3-dibromopropyl) phosphate with restriction in textiles].

The official analytical method for tris(2,3-dibromopropyl)phosphate (TDBPP), which is banned from use in textile products by the "Act on Control of Household Products Containing Harmful Substances", requires revision. This study examined an analytical method for TDBPP by GC/MS using a capillary column. Thermal decomposition of TDBPP was observed by GC/MS measurement using capillary column, unlike in the case of gas chromatography/flame photometric detector (GC/FPD) measurement based on a direct injection method using a capillary megabore column. A quadratic curve, Y=2572X(1.416), was obtained for the calibration curve of GC/FPD in the concentration range 2.0-100 µg/mL. The detection limit was 1.0 µg/mL under S/N=3. The reproducibility for repetitive injections was satisfactory. A pretreatment method was established using methanol extraction, followed by liquid-liquid partition and purification with a florisil cartridge column. The recovery rate of this method was ～100%. TDBPP was not detected in any of the five commercial products that this study analyzed. To understand the cause of TDBPP decomposition during GC/MS (electron ionization; EI) measurement using capillary column, GC/MS (chemical ionization; CI), GC/FPD, and gas chromatography/flame ionization detector (GC/FID) measurements were conducted. It was suggested that TDBPP might thermally decompose both during GC injection, especially through a splitless injection method, and in the column or ion sources. To attempt GC/MS measurement, an injection part comprising quartz liner was used and the column length was halved (15 m); thus, only one peak could be obtained.

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-Whitney's 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-Whitney's 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.

[Examination of analytical method for triphenyltin (TPT) and tributyltin (TBT) to revise the official methods based on "Act on the Control of Household Products Containing Harmful Substances"].

The use of triphenyltin (TPT) and tributyltin (TBT) in some household products is banned by "Act on the Control of Household Products Containing Harmful Substances" in Japan. To revise the official analytical method, the method for detecting these organotin compounds was examined in six laboratories using a textile product, water-based adhesive, oil-based paint, which contained known amounts of TPT and TBT (0.1, 1.0, 10 µg/g). TPT and TBT were measured by GC-MS after ethyl-derivation with sodium tetraethylborate. The TBT recoveries in the samples were 70-120%. The TPT recoveries in the water-based adhesive samples were 80-110%, while its concentrations in the textile product and oil-based paint samples decreased because of dephenylation during storage. However, the precision of the method examined was satisfactory because most coefficients of variation for TPT and TBT in the samples were less than 10%. Furthermore, the revised method was able to detect concentrations lower than the officially regulated value. However, the sample matrix and the condition of analytical instrument might affect the estimated TPT and TBT concentrations. Therefore, the revised method may not be suitable for quantitative tests; rather, it can be employed to judge the acceptable levels of these organotin compounds by comparing the values of control sample containing regulated amounts of TPT and TBT with those for an unknown sample, with deuterated TPT and TBT as surrogate substances. It is desirable that TPT in textile and oil-based paint samples are analyzed immediately after the samples obtained because of the decomposition of TPT.

Detection of Dechlorane Plus and brominated flame retardants in marketed fish in Japan.

Fish samples purchased from Japanese markets were analyzed for Dechlorane Plus (DP)(syn-, anti-), polybrominated diphenyl ether (PBDE), and hexabromocyclododecane (HBCD)(α, γ). Twenty fish were analyzed using gas chromatography-mass spectrometry for DP and PBDE, and using liquid chromatography-tandem mass spectrometry for HBCD. DP was detected in 18 samples and ∑DP concentrations were <0.2-14.2 pg g(-1)wet wt. Among the DP isomers, anti-DP was the dominant residue observed in this study. PBDE was detected in all samples. Concentrations of ∑PBDE ranged from 2.2 to 878 pg g(-1) wet wt. HBCD was detected in 18 samples, and ∑HBCD concentrations were <0.02-21.9 ng g(-1)wet wt. In fish landed near the East China Sea and the Sea of Japan, we detected relatively high concentrations of DP, PBDE, and HBCD. These results indicate that the seawaters around East Asia are contaminated with flame retardants. This study demonstrates the presence of DP in fish marketed in Japan for the first time.

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.

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.

Ortho-phthalaldehyde exposure levels among endoscope disinfection workers.

OBJECTIVES AND METHODS: Recently, the use of ortho-phthalaldehyde (OPA) has been increasing as an alternative to glutaraldehyde for endoscope disinfection. To better understand OPA exposure and its health effects among disinfection workers, we conducted environmental monitoring and administered a questionnaire in 17 endoscope disinfection rooms. There were 9 manual disinfection rooms using immersion vats for scope disinfection and 8 automatic rooms using automatic washers. RESULTS: OPA exposure concentration during the disinfection process of scope was significantly higher in the manual group (median: 1.43ppb, range: not detected (ND-5.37ppb) than in the automatic group (median: 0.35 ppb, range: ND-0.69 ppb). Similarly, during charging and discharging the antiseptic solution, OPA levels were significantly higher in the manual group (median: 2.58 ppb, range: 0.92-10.0 ppb) than in the automatic group (median: 0.46ppb, range: ND-1.35 ppb). Time-weighted averages of OPA exposure concentration during work shifts were 0.33 to 1.15 ppb (median 0.66 ppb) in the manual group and 0.13 to 1.28 ppb (median 0.33 ppb) in the automatic group, which suggests that manual workers are exposed to OPA at higher levels. Among 80 female disinfection workers who used only antiseptic solutions containing OPA, the incidence of disinfection-related complaints were 10% skin, 9% eye, and 16% respiratory symptoms. CONCLUSIONS: These findings suggest that it is desirable to introduce automatic washers to decrease OPA exposure levels among disinfection workers.

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-Whitney's 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-Whitney's 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 (Wilcoxon's 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.

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

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.

[Low back load and satisfaction rating of caregivers & care receivers in bathing assistance given in a nursing home for the elderly practicing individual care].

Since the public nursing care insurance system was enacted by the Japanese government, a transition from conventional group treatment to the individual care is required. In Japanese nursing homes for the elderly, bathing assistance methods have shifted from use of traditional mechanical bathtubs or a big bathtub to methods using small homestyle bathtubs, known as "individual bathing assistance". A study on the work load of caregivers with individual bathing assistance has never been conducted. Therefore, in a nursing home for the elderly practicing the individual bathing assistance method, we explored low back load using surface electromyography and trunk inclination angle measurement. Moreover, subjective evaluations by not only the caregivers but also the care receivers were investigated. The individual bathing assistance time per person was about 35 min. When caregiver used the mechanical lift equipment to assist getting into and out of the bathtub, trunk inclination angle and muscle load were lower than with manual handling. Mechanical lift equipment had the advantage of reducing low back load. When caregivers gave assistance with dressing and ablution of the lower limbs, and in setting wheelchair footrests, trunk inclination angle and muscle load showed high values. The satisfaction rating of using the mechanical lift equipment showed the best score, and ratings of perceived exertion were about the same. Thus, the importance of safe and comfortable care for both caregivers and care receivers should be stressed to make effective use of assistance products and care equipment.

Genotoxic risks to nurses from contamination of the work environment with antineoplastic drugs in Japan.

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 microm, respectively, for the exposed and control groups, with a significant difference (p=0.004 by Mann-Whitney's 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.

[Equipment at the special nursing homes for the elderly: a workplace survey of new nursing homes in Osaka Prefecture].

The number of those who need nursing care and the workers who provide it have been increasing year after year. In April 2000, the public nursing care insurance system was enacted by the Japanese government. After its enaction, care equipment came under scrutiny, but the situation regarding the installation of equipment is not fully understood. In order to understand the present state of care equipment in nursing facilities for the elderly, we conducted a workplace and interview survey. The surveyed facilities were 10 special nursing homes for the elderly in Osaka Prefecture which were established after April 2002. The average number of elderly residents was 79.0, the average value of degree of care was 3.52, and the average number of caregivers was 28.3 per facility. We found all facilities had installed some kinds of bathing equipment: stretcher type, 9 facilities; bath-chair type, 8 facilities. In the facilities with bath-chairs, 6 facilities had special bathtubs, and 6 facilities had general bathtubs. However, all facilities had the working principle that transfer should be done manually, and the equipment for transfer such as a lifts, a transfer and roller board were not be installed. In changing diapers, bed height adjustment was not possible. And the Japanese standard type of wheelchair has a non-detachable armrest, creating a structural barrier when transferring elderly people from a wheelchair to a toilet seat. At all facilities the basis of care was that caregivers should do it manually. In particular, all facilities had only a weak recognition of the risks of transfer. This investigation shows that facilities for the elderly should rethink elderly care based on a reduction of care load and most importantly protection of caregivers' health.

Negative association between serum dioxin level and oxidative DNA damage markers in municipal waste incinerator workers.

OBJECTIVES: To investigate the effect of dioxin on the formation of oxidative DNA damage and urinary mutagenicity, we measured the concentrations of serum dioxins and lymphocytic 8-hydroxydeoxyguanosine (8-OH-dG) in 57 male waste incinerator workers, urinary 8-OH-dG and urinary mutagenicity in 29 male waste incinerator workers. METHODS: Information about the subjects was obtained from a questionnaire. Concentrations of polychlorinated dibenzo-p-dioxin (PCDD), polychlorinated dibenzofuran (PCDF), and coplanar-polychlorinated-biphenyl (Co-PCB) in serum samples from the workers were measured with a high-resolution gas chromatograph /high-resolution mass spectrometer. Lymphocytic and urinary 8-OH-dG levels were measured with a high-performance liquid chromatography-electrochemical detector system. The urinary mutagenicity was measured with umu assay. RESULTS: The lymphocytic 8-OH-dG level showed a negative association with the serum dioxin level (total value of TEQ-PCDD, PCDF, and Co-PCB). Urinary 8-OH-dG did not show correlation with serum dioxin level, but showed positive correlation with the smoking index. CONCLUSIONS: With respect to the subjects' serum dioxin level, dioxin did not increase the urinary 8-OH-dG level by oxidative DNA damage, but upregulation of the primary defenses with oxidative damage and/or DNA repair system activity might have occurred.

[Load on the low back of care workers in nursing homes for the elderly].

In order to evaluate the load on the low back of care workers in nursing homes for the elderly, basic activities and working postures were analyzed for six care workers using the 30-s snap reading method. The trunk inclination angle (TIA) was also measured continuously using an inclination monitor. The analysis of basic activities showed that 22.5% and 21.1% of the workshift were spent on 'bathing and ablution' and 'meal', respectively, and 9.3%, 8.7% and 8.3% were spent on 'assistance with elimination', 'assistance with moving and repositioning' and 'exchange of bed sheet', respectively. Total of the assistance activity was 43.7% of the workshift. The analysis of working posture showed that 'standing' and 'standing bent forward' accounted for 36.1% and 29.5%, respectively, of the workshift. Total of three postures loading the low back ('standing bent forward', 'squatting', 'kneeling') accounted for 39.0%. The time spent in TIA of 20 degrees or more was 45.7%. The postures loading the low back during 'bathing and ablution', 'exchange of bed sheet' and 'assistance with elimination' account for 68.3%, 58.2% and 49.6%, respectively, which suggests that these activities load the low back of the care workers considerably.

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, 17beta-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.

[Relationships between dioxin concentrations in deposited dust and those in serum of workers at municipal waste incineration plants].

Relationships between concentrations of polychlorodibenzo-p-dioxins (PCDDs) and polychlorodibenzofurans (PCDFs) in deposited dust and those in the serum of incinerator workers were examined at 13 municipal incineration plants. The following results were found. 1) Dust analysis showed that dominant constituents were octachlorodibenzo-p-dioxin (OCDD) and 1, 2, 3, 4, 6, 7, 8-heptachlorodibenzo-p-dioxin (HpCDD) among PCDDs, and 1, 2, 3, 4, 6, 7, 8-heptachlorodibenzofuran (HpCDF) and octachlorodibenzofuran (OCDF) among PCDFs. The toxicity equivalents (TEQs) of total PCDDs and PCDFs in the deposited dust were 0.54 to 33 ngTEQ/g, which were about 1,000 to 10,000 times as high as those in general soil. 2) The mean of serum TEQ of PCDDs, that of PCDFs and that of total PCDDs and PCDFs in the incinerator workers were 16, 12 and 28 pg TEQ/g lipid, respectively, for all the incinerator workers. Concentrations of hexachlorodibenzofurans (HxCDFs) and HpCDFs in the serum were significantly higher in the incinerator workers than the general population, which suggests that these workers had inhaled these chemicals during their work. 3) The concentration of 1, 2, 3, 4, 6, 7, 8-HpCDF and the TEQ value of PCDFs and in the serum were positively correlated with those in dust except for three plants where large-scale remodeling of the equipment was conducted within the past seven years. Consequently, deposited dust analysis may be useful for judging whether health examination containing blood dioxin measurement is necessary or not.