Hiroshi Kosaka

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.

Correlation between lead in plasma and other indicators of lead exposure among lead-exposed workers.

In order to clarify the bioavailability of lead in plasma (PbP), we performed a study on five workers in a Japanese factory manufacturing lead glass-based paints. Blood and urine samples were obtained over a period of 15 months, during which time the workers took it in turns to perform sifting work (with the highest level of lead exposure) for 1-month periods. A total of 75 sets of blood and urine samples were thus obtained. We determined whole blood lead (PbB), PbP, Urinary coproporphyrin (CPU), urinary δ-aminolevulinic acid (ALAU), urinary lead (PbU) and ALA in plasma (ALAP). In the 15 sets of samples obtained at the end of the period with a high level of lead exposure, PbP correlated significantly with ALAU, CPU, PbU and ALAP, but PbB correlated significantly only with PbU. In the 60 sets of samples obtained following a low level of lead exposure, correlation coefficients between the concentrations of PbP and of ALAU, CPU and PbU exceeded those between the concentrations of PbB and of ALAU, CPU and PbU. These findings indicate that PbP is a better dose indicator of lead biochemically available for heme synthesis and that PbU has a closer correlation with PbP than with PbB.

Load on the low back of teachers in nursery schools

In order to evaluate the load on the low back of teachers in nursery schools, basic activity, working posture, child-lifting, and desk-lifting were analyzed for eight nursery teachers using video recording. The trunk inclination angle (TIA) was also measured continuously during full workshifts for 20 nursery teachers using an inclination monitor. The nursery teachers in the 0–1 (year) age class more often adopted low working postures, “sitting on the floor” and “kneeling,” while teachers in the 4–5 age class more frequently adopted high working postures, “standing” and “sitting on a chair.” The mean of TIA among all subjects was 20°. The time spent at a TIA of more than 20° represented 43% of the workshift. The mean and time distribution of TIA did not differ between the age classes. The frequency of trunk-lifting from severe bending forward (TIA > 45°) was 86 times/hour on average. The frequency of trunk-lifting was highest in the 0–1 age class. The number of times of child-lifting was 46 in the 0–1 age class, while it was 1 in the 4–5 age class.

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.

Study on measurement of δ-aminolevulinic acid in plasma by high-performance liquid chromatography

A method for the determination of δ-aminolevulinic acid in plasma of lead-exposed workers by high-performance liquid chromatography with fluorescence detection of a fluorescent δ-aminolevulinic acid derivative (2-methylidineamino-3,5-diacetyl-4,6-dimethylpropionic acid) was established. The detection limit of δ-aminolevulinic acid in plasma was 0.01 μg/ml at a signal-to-noise ratio of 5:1. A linear correlation was obtained between the amounts of δ-aminolevulinic acid injected from 0.01 to 0.5 μg/ml (r = 0.999). The recovery of 0.05 and 0.1 μg/ml of δ-aminolevulinic acid added to plasma with various concentrations of δ-aminolevulinic acid in plasma ranged from 80.0 to 100.8%. This method, combined with the use of an automatic sampler, should facilitate the routine measurement of δ-aminolevulinic acid in plasma.

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.

Effects of Lead Exposure on Neurophysiological Parameters

To clarify the chronic effect of lead exposure on the central and peripheral nervous systems (CNS and PNS), we performed neurophysiological tests on 41 lead-exposed male workers. Unexposed workers (controls, N = 39) were examined for auditory brain stem response (ABR), and their ABR parameters were compared with those of 15 lead-exposed workers age-matched to the controls. Neurophysiological tests included those of motor and sensory nerve conduction velocity of the radial nerve (MCV, SCVwa and SCVfw), electroretinograms, pattern reversal visual evoked potential (VEP), ABR, and short-latency somatosensory evoked potentials (SLSEP). Neurophysiological parameters were analyzed by regression analysis [independent parameters: age, exposure duration, and current and time-weighted average lead concentration in whole blood (PbB and TWA-PbB)]. ABR parameters were also tested by Students t test. Significant negative correlations were found between radial MCV and TWA-PbB and SCVwa and PbB, while significant positive correlations were found between the latency of component N145 of VEP and exposure duration and between the latency of component N20 of SLSEP and PbB. The mean of interpeak latency between component III and V of ABR of 15 lead-exposed workers was significantly prolonged compared with that of the control group. These results suggested that lead exposure has a greater effect on the conduction function in the PNS than in that of the CNS in somatosensory and auditory pathways, and inversely in visual pathway.

Genotoxicity of synthetic dyes with umu test using Salmonella typhimurium TA1535/pSK1002. (II).

In the present study, SOS-inducing activity of 76 basic dyes was investigated by umu test using Salmonella typhimurium TA1535/pSK1002 under the condition of absence and presence of rat liver microsomal fraction. The test was carrid out with five doses of basic dyes (400, 120, 40, 12, and 4 μg/ml). The samples showing β-galactosidase activity more than 1.5-fold over the background level were reexamined and the dose-response curves were prepared at various doses. Thereafter, samples showing β-galactosidase activity unit more than 1.5-fold of the background level were defined as genotoxic. Among the basic dyes examined, 13 compounds induced umu gene expression. The potent genotoxic compounds without metabolic activation were Blue 40, Blue 47, Brown 14, Orange 30, Red 24, Violet 30, Violet 31, Yellow 13 (h), Yellow 19, Yellow 25, Yellow 67, and Yellow 73 and in the presence of S9, Orange 47 was judged as genotoxic in addition to the aforementioned dyes. An evident dose-response relationship between the doses of the dye and umu gene expression was observed in these 13 dyes.