A further cohort study of workers employed at a factory manufacturing chemicals for the rubber industry, with special reference to the chemicals 2-mercaptobenzothiazole (MBT), aniline, phenyl-beta-naphthylamine and o-toluidine.
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OBJECTIVES: To investigate mortality and cancer morbidity in workers from a factory manufacturing chemicals for the rubber industry. METHODS: The mortality (1955-96) and cancer morbidity experience (1971-92) of a cohort of 2160 male production workers from a chemical factory in north Wales were investigated. All subjects had at least 6 months employment at the factory and some employment in the period 1955-84. Detailed job histories were abstracted from company computerised records and estimates of individual cumulative exposure to 2-mercaptobenzothiazole (MBT) and its derivatives were obtained, with a job exposure matrix derived by a former factory hygienist. Durations of employment in the aniline, phenyl-beta-naphthylamine (PBN) and o-toluidine departments were also calculated. Two analytical approaches were used, indirect standardisation and Poisson regression. RESULTS: Based on serial rates for the general population of England and Wales, observed mortality for the total cohort was close to expectation for all causes (observed (obs) deaths 1131, expected (exp) deaths 1114.5, standardised mortality ratio (SMR) 101), and for all cancers (obs 305, exp 300.2, SMR 102). There was a significant (p < 0.05) excess mortality from cancer of the bladder in the 605 study subjects potentially exposed to one or more of the four chemicals being investigated (obs 9, exp 3.25, SMR 277, 95% confidence interval (95% CI) 127 to 526). This excess was dependent primarily on deaths occurring > 20 years after first exposure in those who started employment before 1955 (obs 7, exp 1.25, SMR 560, 95% CI 225 to 1154, p < 0.001). There were 30 subjects in the total study cohort who, on the basis of death certificates or cancer registration particulars, had had malignant bladder cancer. In separate analyses of the four exposure history variables (after adjustment for age), Poisson regression showed significant positive trends for risk of notification of bladder cancer increasing with cumulative duration of employment in the PBN (p < 0.001) and o-toluidine departments (p < 0.01); similar findings were not obtained for cumulative exposure to MBT or for duration of employment in the aniline department. In a simultaneous analysis of all four chemical exposure variables, a significant positive trend remained for duration of employment with exposure to PBN (p < 0.05). Further analyses of all cases of bladder cancer (malignant and benign diagnoses) used employment histories lagged by 15 years; similar findings were obtained. CONCLUSIONS: It seems likely that some members of this cohort have had occupational bladder cancer. Confident interpretation is difficult because of small numbers in the exposed subcohorts, relatively crude measures of exposure assessment for the four chemicals under study, and presence of unconsidered potential chemical confounders. The simplest interpretation of the findings about bladder cancer may be that PBN (or a chemical reagent or chemical intermediate associated with its production at this factory in the 1930s and 1940s) is a bladder carcinogen. Priority should be given, however, to obtaining information on the cancer experience of other working populations exposed to PBN or to o-toluidine. (+info)
A liquid-stable reagent for lactic acid levels. Application to the Hitachi 911 and Beckman CX7.
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We evaluated the use of a new lactate oxidase-based reagent for the determination of serum and plasma lactic acid levels with the Hitachi 911 (Roche Diagnostics, Indianapolis, IN) and the Beckman CX7 (Beckman Instruments, Brea, CA). Evaluation studies demonstrated on-board stability of at least 3 months and a calibration stability of more than 5 months. Within- and between-day imprecision of this reagent was less than 2% for both applications. The reagent is free of the deleterious effects of triglyceride up to levels of 1,400 mg/dL (15.8 mmol/L), bilirubin to concentrations of 24.6 mg/dL (420 mumol/L), and hemoglobin, from lysed erythrocytes, to levels of more than 0.3 g/dL (3.0 g/L). When used on the Hitachi 911 for the determination of plasma lactate concentrations, the reagent correlates with the Dade aca III (Dade International, Deerfield, IL). When applied to the Beckman CX7 for the determination of serum lactate levels, the method correlates with the Beckman method. (+info)
A more complete evaluation of the color-coded antigen for the automated reagin test.
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A comparative study, on 500 samples, of the toluidine red antigen, one of the low-cost, color-coded antigens for the Automated Reagin Test, shows a greater sensitivity than the rapid plasma reagin card antigen. (+info)
Comparative metabolism of chloroacetamide herbicides and selected metabolites in human and rat liver microsomes.
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Acetochlor [2-chloro-N-(ethoxymethyl)-N-(2-ethyl-6-methyl-phenyl)-acetamide], alachlor [N-(methoxymethyl)-2-chloro-N-(2, 6-diethyl-phenyl)acetamide], butachlor [N-(butoxymethyl)-2-chloro-N-(2,6-diethyl-phenyl)acetamide], and metolachlor [2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-1-methylethyl) acetamide] are pre-emergent herbicides used in the production of agricultural crops. These herbicides are carcinogenic in rats: acetochlor and alachlor cause tumors in the nasal turbinates, butachlor causes stomach tumors, and metolachlor causes liver tumors. It has been suggested that the carcinogenicity of these compounds involves a complex metabolic activation pathway leading to a DNA-reactive dialkylbenzoquinone imine. Important intermediates in this pathway are 2-chloro-N-(2,6-diethylphenyl)acetamide (CDEPA) produced from alachlor and butachlor and 2-chloro-N-(2-methyl-6-ethylphenyl)acetamide (CMEPA) produced from acetochlor and metolachlor. Subsequent metabolism of CDEPA and CMEPA produces 2,6-diethylaniline (DEA) and 2-methyl-6-ethylaniline (MEA), which are bioactivated through para-hydroxylation and subsequent oxidation to the proposed carcinogenic product dialkylbenzoquinone imine. The current study extends our earlier studies with alachlor and demonstrates that rat liver microsomes metabolize acetochlor and metolachlor to CMEPA (0.065 nmol/min/mg and 0.0133 nmol/min/mg, respectively), whereas human liver microsomes can metabolize only acetochlor to CMEPA (0.023 nmol/min/mg). Butachlor is metabolized to CDEPA to a much greater extent by rat liver microsomes (0.045 nmol/min/mg) than by human liver microsomes (< 0.001 nmol/min/mg). We have determined that both rat and human livers metabolize both CMEPA to MEA (0.308 nmol/min/mg and 0.541 nmol/min/mg, respectively) and CDEPA to DEA (0.350 nmol/min/mg and 0.841 nmol/min/mg, respectively). We have shown that both rat and human liver microsomes metabolize MEA (0.035 nmol/min/mg and 0.069 nmol/min/mg, respectively) and DEA (0.041 nmol/min/mg and 0.040 nmol/min/mg, respectively). We have also shown that the cytochrome P450 isoforms responsible for human metabolism of acetochlor, butachlor, and metolachlor are CYP3A4 and CYP2B6. (+info)
Study of resin-bonded calcia investment: Part 1. Setting time and compressive strength.
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This study was carried out to develop a new titanium casting investment consisting of calcia as the refractory material and a cold-curing resin system as the binder. The setting time of the investment was investigated under different N,N-dimethyl-p-toluidine (DMPT) contents in methyl methacrylate monomer (MMA) and benzoyl peroxide (BPO) contents in calcia without any sintering agent. The effects of the sintering agents, which were calcium fluoride (CaF2) and calcium chloride (CaCl2), on the compressive strength of the investments were investigated at room temperature before and after heating to two different temperatures. The shortest setting time (68 minutes) of the investment was obtained at 0.37 DMPT/BPO (1.5 vol% /1.0 mass%) ratio by mass. The highest strength (16.5 MPa) was obtained from the investment which contained 2 mass% CaF2 and was heated to 1,100 degrees C. It was found that the developed calcia investment containing 2 mass% CaF2 has a possibility for use in titanium castings. (+info)
Thermochemical determination of glucose in serum, plasma, and whole blood without prior deproteinization.
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Glucose can be determined by phosphorylation in the presence of hexokinase (EC 2.7.1.1) by using Mg2+/(ATP)2- as the phosphorylating agent. A novel instrumental quantitation method is described, direct injection enthalpimetry, whereby the heat of the enzymatically catalyzed reaction was measured. The reaction was allowed to proceed to virtual completion (99.5+%) in an adiabatic Dewar vessel at 25.00 plus or minus 0.01 degrees C (range). Samples were sequentially injected into a reaction mixture consisting of hexokinase, ATP, Mg2+, and a tris(hydroxymethyl)aminomethane buffer (pH 8). Single analyses required less than 2 min for 0-3 g/liter samples. The linear dynamic range was 0.3-10 g/liter, with zero intercept and a precision and accuracy of 2%. Electrical calibration in situ obviated the need for chemical standards, and because protein and color do not interfere, no sample pretreatment was necessary before analysis. (+info)
Histamine induces exocytosis and IL-6 production from human lung macrophages through interaction with H1 receptors.
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Increasing evidence suggests that a continuous release of histamine from mast cells occurs in the airways of asthmatic patients and that histamine may modulate functions of other inflammatory cells such as macrophages. In the present study histamine (10(-9)-10(-6) M) increased in a concentration-dependent fashion the basal release of beta-glucuronidase (EC(50) = 8.2 +/- 3.5 x 10(-9) M) and IL-6 (EC(50) = 9.3 +/- 2.9 x 10(-8) M) from human lung macrophages. Enhancement of beta-glucuronidase release induced by histamine was evident after 30 min and peaked at 90 min, whereas that of IL-6 required 2-6 h of incubation. These effects were reproduced by the H(1) agonist (6-[2-(4-imidazolyl)ethylamino]-N-(4-trifluoromethylphenyl)heptane carboxamide but not by the H(2) agonist dimaprit. Furthermore, histamine induced a concentration-dependent increase of intracellular Ca(2+) concentrations ([Ca(2+)](i)) that followed three types of response, one characterized by a rapid increase, a second in which [Ca(2+)](i) displays a slow but progressive increase, and a third characterized by an oscillatory pattern. Histamine-induced beta-glucuronidase and IL-6 release and [Ca(2+)](i) elevation were inhibited by the selective H(1) antagonist fexofenadine (10(-7)-10(-4) M), but not by the H(2) antagonist ranitidine. Inhibition of histamine-induced beta-glucuronidase and IL-6 release by fexofenadine was concentration dependent and displayed the characteristics of a competitive antagonism (K(d) = 89 nM). These data demonstrate that histamine induces exocytosis and IL-6 production from human macrophages by activating H(1) receptor and by increasing [Ca(2+)](i) and they suggest that histamine may play a relevant role in the long-term sustainment of allergic inflammation in the airways. (+info)
Enhanced tolerance of transgenic poplar plants overexpressing gamma-glutamylcysteine synthetase towards chloroacetanilide herbicides.
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A wild-type poplar hybrid and two transgenic clones overexpressing a bacterial gamma-glutamylcysteine synthetase in the cytosol or in the chloroplasts were exposed to the chloroacetanilide herbicides acetochlor and metolachlor dispersed in the soil. The transformed poplars contained higher gamma-glutamylcysteine and glutathione (GSH) levels than wild-type plants and therefore it was supposed that they would have an elevated tolerance towards these herbicides, which are detoxified in GSH-dependent reactions. Phenotypically, the transgenic and wild-type plants did not differ. The growth and the biomass of all poplar lines were markedly reduced by the two chloroacetanilide herbicides. However, the decrease of shoot and root fresh weights caused by the herbicides was significantly smaller in the transgenic than in wild-type plants. In addition, the growth rate of poplars transformed in the cytosol was reduced to a significantly lesser extent than that of wild-type plants following herbicide treatments. The effects of the two herbicides were similar. Herbicide exposures markedly increased the levels of gamma-glutamylcysteine and GSH in leaves of each poplar line. The increase in the foliar amounts of these thiols was stronger in the transgenic lines than in the wild type, particularly in the upper leaves. Considerable GST activities were detected in leaves of all poplar plants. Exposure of poplars to chloroacetanilide herbicides resulted in a marked induction of GST activity in upper leaf positions but not in middle and lower leaves. The extent of enzyme induction did not differ significantly between transgenic and wild-type poplars. Although the results show that the transgenic poplar lines are good candidates for phytoremediation purposes, the further improvement of their detoxification capacity, preferably by transformation using genes encoding herbicide-specific GST isoenzymes, seems to be the most promising way to obtain plants suitable for practical application. (+info)