An alternative vapor was explored to replace carbon tetrachloride (CCl4) for testing breakthrough times of cartridges and canisters of gas masks in the National Approval Test of Respirators. Cyclohexane was single out as a candidate for the alternative vapor out of six vapors: trichloroethylene, n-pentane, n-hexane, n-heptane, toluene and cyclohexane from the viewpoints of similarity of vapor pressure and water-solubility to CCl4, lower toxicity than CCl4, and technical feasibility in generating an airflow of 30 L/min containing the vapor ranging from 300 to 5000 ppm. Breakthrough times of cartridges and canisters were examined by generating cyclohexane vapor in a test airflow of 30 L/min in comparison with CCl4 vapor under various test conditions with different vapor concentrations and relative humidities (RH). As the results, the breakthrough times of the cartridges and canisters for cyclohexane were found to almost coincide with those for CCl4 under all examined range of concentrations and RH. By an increase of humidity from 50%RH to 80%RH, the cartridges showed significant shortening of breakthrough times for both of CCl4 and cyclohexane, but the susceptibility of the breakthrough time of cyclohexane to humidity was also similar to that of CCl4. It was, therefore, concluded that cyclohexane can be recommended as the alternative vapor of CCl4 for testing the breakthrough times of gas mask cartridges and canisters in the National Approval Test.
To clarify acute toxicity and histopathological changes in the lung after exposure to V2O5 powder, rats (SD, male, n=66) were observed for 4 weeks after an intratracheal administration of V2O5 powder (geometric mean diameter 0.31 μm, geomertic standard deviation σg=2.19) at three doses (0.88, 3.0, 13.0 mg/kg body weight). The histopathological lung lesions were developed dosedependently, and characterized by exudative inflammation, injury of alveolar macrophages, and swelling and mucous degeneration in the broncho-bronchiolar epithelia. Growth rate of the V2O5 powder-instilled rat was also retarded dose-dependently. The V2O5 powder used was composed of not coagulated but well dispersed particles consisting of vanadium pentoxide of more than 99.8% (w/w) with vanadium tetraoxide of less than 0.2%. The V2O5 powder was found to be 8 times more soluble in an artificial biological fluid “Gamble's solution” than in a pure water. From the present findings as well as those from the related literature, it was inferred that the histopathological lesions induced by the intratracheally instilled V2O5 powder are caused not only by the V2O5 particles per se but also by vanadium ions dissolved from the particles into the lung fluid.
The association of hematocrit with development of hypertension over 9 years was studied in 784 hypertension-free Japanese men aged 40 to 59 years. The age-adjusted relative risk for hypertension above the borderline level and definite hypertension increased in a dose-dependent manner as hematocrit level increased (P for trend: 0.007 and 0.001, respectively). After controls for other potential factors of hypertension, the test for trend across increasing categories of hematocrit level remained as statistical significance for definite hypertension (P=0.015). The multivariate-adjusted relative risk for definite hypertension compared with less than 43.8% of hematocrit level was 1.29 [95% confidence interval (CI): 0.62-2.67] for 43.8 to 45.2% hematocrit level, 1.35 (95% CI: 0.62-2.95) for 45.3 to 46.3% hematocrit level, 1.96 (95% CI: 0.97-3.97) for 46.4 to 48.1% hematocrit level, and 2.06 (95% CI: 1.02-4.15) for 48.2% or more hematocrit level. These results suggest that hematocrit is closely associated with development of hypertension in middle-aged Japanese men.
Inhalation of platinum, as soluble salts, is known to cause respiratory distress and severe dermatitis in workers. Platinum coordination complexes are widely used in the treatment of a variety of solid tumors. However, the clinical use of cisplatin (CDDP) (the most useful agent) is limited by the development of nephrotoxicity. High dose accidental exposure to soluble platinum in platinum refineries and pharmaceutical factories could induce occupational nephrotoxicity. Carboplatin (CBDCA), a second-generation platinum coordination complex, is highly effective against a variety of malignancies at doses five- to ten-times higher than CDDP. At therapeutic doses, CBDCA is less nephrotoxic than CDDP. Additionally, urinary citrate is freely filtered at the glomerulus, and its reabsorption in the proximal tubule is the major determinant of the rate of renal excretion. In our previous study, the preincubation of rat renal brush border membrane vesicles (BBMV) with 5 mM cisplatin for 4 and 8 hours significantly inhibited the citrate uptake compared with that of the control BBMV. In this study, we exposed BBMV to 100 mM carboplatin (twenty-times higher concentration than cisplatin) and examined the citrate uptake characteristics to clarify the toxic mechanism of platinum coordination complexes. The preincubation of BBMV with 100 mM carboplatin for 8 hours also significantly inhibited the citrate uptake compared with that of the control BBMV, but the alterations were not as severe as those with 5 mM cisplatin.
A 9-year longitudinal study was performed to prospectively examine the association falcohol consumption with development of aortic stiffness in 1121 aortic stiffness-free [aortic pulse wave velocity (PWV) of less than 8.0 m/sec] Japanese men aged 35 to 59 years without definite hypertension, hypercholesterolemia, or diabetes. 274 men developed aortic stiffness (aortic PWV of 8.0 m/sec or more) during 8872 person-years follow-up. After controlling for potential predictors of aortic stiffness, the relative risk for increased aortic stiffness compared with non-drinkers was 1.01 [95% confidence interval (CI): 0.62-1.64] for those who drank 0.1 to 22.9 g/day of ethanol, 1.71 (95% CI: 1.12-2.60) for those who drank 23.0 to 45.9 g/day of ethanol, 1.79 (95% CI: 1.18-2.71) for those who drank 46.0 to 68.9 g/day of ethanol, and 2.09 (95% CI: 1.35-3.26) for those who drank 69.0 or more g/day of ethanol (P for trend < 0.001). These results suggest that alcohol consumption is closely associated with development of aortic stiffness.
Human peripheral blood lymphocytes (PBLs) produce metallothioneins (MTs) in response to a variety of heavy metal ions. MTs could therefore be a candidate for a marker that represents the biological effect of heavy metals. Since it is practically difficult to measure MT protein levels in PBLs, we examined if MT-mRNA could serve as a biomarker of heavy metal exposure. It is difficult to obtain RNA from PBLs without degradation, but we found that intact RNA can be prepared by the acid guanidinium thiocyanate-phenol-chloroform extraction method which minimizes nuclease digestion of RNA during purification steps. By Northern blot analysis of RNA isolated by this method from PBLs cultured with or without CdSO4, we demonstrated that MT-mRNA is induced by 0.1 to 0.5 μM CdSO4 in a dose-dependent manner. The blood cadmium levels of exposed humans have been reported to be up to 0.5 μM. This suggests that our assay is able to detect quantitative changes in the PBL MT-mRNA level resulting from in vivo cadmium exposure. Thus, PBL MT-mRNA could be used as a sensitive biomarker reflecting exposure to cadmium, and probably to several other MTinducing heavy metals.
A 19-year-old man suffered hepatic dysfunction after 5 months of exposure to N, Ndimethylformamide (DMF) at his job in the synthetic resins industry. Laboratory data revealed elevated levels of AST (578 IU/l), ALT (1193 IU/l), and γ-GTP (107 IU/l), no viral infection with HAV, HBV, or HCV, and no history or evidence of hepatic injury, although he did have a slight abdominal abnormality and swelling which was detected by palpation. His urinary N-methylformamide level, as a biological exposure index of DMF, was 42.8 mg/l, indicating 10-30 ppm of DMF exposure. After 2 months he was reinstated in two workplaces, the former where he worked in the morning and the other in the afternoon where environmental DMF concentrations were less than those in the former workplace. On the 18th day after his reinstatement, his liver function became exasperated again. After the second period of medication and one month of rest from work, he had fully recovered and was reinstated, but to a workshop without DMF exposure.