[Protective action of toxogonin and TMB-4 in experimental tabun poisoning].
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Animals↗
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[Trimethoxybenzene (TMB) test. Search for evaluation of hepatocytic metabolic function in clinical practice].
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Adult↗
Molecular analysis of a Saccharomyces cerevisiae mutant with improved ability to utilize xylose shows enhanced expression of proteins involved in transport, initial xylose metabolism, and the pentose phosphate pathway.
Differences between the recombinant xylose-utilizing Saccharomyces cerevisiae strain TMB 3399 and the mutant strain TMB 3400, derived from TMB 3399 and displaying improved ability to utilize xylose, were investigated by using genome-wide expression analysis, physiological characterization, and biochemical assays. Samples for analysis were withdrawn from chemostat cultures. The characteristics of S. cerevisiae TMB 3399 and TMB 3400 grown on glucose and on a mixture of glucose and xylose, as well as of S. cerevisiae TMB 3400 grown on only xylose, were investigated. The strains were cultivated under chemostat conditions at a dilution rate of 0.1 h(-1), with feeds consisting of a defined mineral medium supplemented with 10 g of glucose liter(-1), 10 g of glucose plus 10 g of xylose liter(-1) or, for S. cerevisiae TMB 3400, 20 g of xylose liter(-1). S. cerevisiae TMB 3400 consumed 31% more xylose of a feed containing both glucose and xylose than S. cerevisiae TMB 3399. The biomass yields for S. cerevisiae TMB 3400 were 0.46 g of biomass g of consumed carbohydrate(-1) on glucose and 0.43 g of biomass g of consumed carbohydrate(-1) on xylose. A K(s) value of 33 mM for xylose was obtained for S. cerevisiae TMB 3400. In general, the percentage error was <20% between duplicate microarray experiments originating from independent fermentation experiments. Microarray analysis showed higher expression in S. cerevisiae TMB 3400 than in S. cerevisiae TMB 3399 for (i) HXT5, encoding a hexose transporter; (ii) XKS1, encoding xylulokinase, an enzyme involved in one of the initial steps of xylose utilization; and (iii) SOL3, GND1, TAL1, and TKL1, encoding enzymes in the pentose phosphate pathway. In addition, the transcriptional regulators encoded by YCR020C, YBR083W, and YPR199C were expressed differently in the two strains. Xylose utilization was, however, not affected in strains in which YCR020C was overexpressed or deleted. The higher expression of XKS1 in S. cerevisiae TMB 3400 than in TMB 3399 correlated with higher specific xylulokinase activity in the cell extracts. The specific activity of xylose reductase and xylitol dehydrogenase was also higher for S. cerevisiae TMB 3400 than for TMB 3399, both on glucose and on the mixture of glucose and xylose.
Biological Transport↗
Biological monitoring of experimental human exposure to trimethylbenzene.
Trimethylbenzene (TMB) is a component of numerous commercial preparations of organic solvents (Farbasol, Solvesso, Shellsol) used in the chemical, plastics, printing and other industries. TMB is a mixture of three isomers (pseudocumene-1,2,4-TMB; mesitylene-1,3,5-TMB; hemimellitene-1,2,3-TMB). The proportion of individual isomers in the mixture differs. The aim of this study was to obtain toxicokinetic data on the absorption and elimination of trimethylbenzene and its metabolites in biological fluids and to investigate the relationship between the biological indices of exposure and the absorbed dose. Eight-hour inhalation tests were performed in a toxicological chamber, The subjects were eight volunteers aged 20-39 with no history of exposure to TMB. They were exposed to pseudocumene, mesitylene or hemimellitene at concentrations ranging from 5 to 150 mg/m3 air. Exhaled air, capillary blood and urine samples were collected before, during and after the exposure. The determinations of TMB or its metabolites were performed using gas chromatography (HP 5890 II Plus, MSD, FID). Pulmonary ventilation in the volunteers ranged from 0.56 to 1.0 m3/h. The retention of 1,2,4-TMB; 1,3,5-TMB; 1,2,3-TMB in the lungs was 68%, 67% and 71%, respectively. The elimination of TMB from capillary blood occurred in accordance with the open three-compartment model. Urinary excretion of dimethylbenzoic acids (DMBA) proceeded according to the open two-compartment model. Based on the toxicokinetic data, a simulation model of accretion and excretion of DMBA in urine during a 14-day period was developed. The highest rates of metabolite excretion and the highest quantities of DMBA in urine during 24-h intervals were observed on day 5 of exposure. The relationship between the levels of TMB or DMBA in biological material and TMB air concentration or absorbed dose were determined. To select the urine fraction suitable for determining occupational TMB exposure, linear regression analysis was performed. The biological exposure limit (BEL) for TMB has been proposed, with the current maximum allowable concentration (MAC) value of 100 mg/m3 (Polish standard) baseline value.
Absorption↗
Local actions of trimebutine maleate in canine small intestine.
A study of the local actions of trimebutine (TMB) maleate and its N-diesmethyl metabolite (TMB-M) was carried out in the gastrointestinal tract of anesthetized dogs. In the unstimulated small intestine, but not in the stomach or colon, i.a. TMB and TMB-M caused activation of circular muscle. Like the activation by i.a. [Met5]-enkephalin, this was antagonized by naloxone. In field-stimulated segments of stomach and small intestine circular muscle, TMB or TMB-M, like dynorphin-1-13 or [Met5]-enkephalin, inhibited the phasic and tonic contractions which were mediated mostly by cholinergic, postganglionic nerves. However, the inhibitory effects of dynorphin-1-13 or [Met5]-enkephalin on small intestine were antagonized by naloxone whereas those of TMB sometimes or those of TMB-M usually were not. TMB or TMB-M did not affect responses to i.a. acetylcholine, but high doses reduced the contractile responses to subsequent field stimulation and excitatory responses to [Met5]-enkephalin. We concluded that the excitatory local actions of TMB or TMB-M on small intestine involved opioid receptors probably of the mu or delta types. Inhibitory local actions on nerve-mediated responses, however, may not have involved opioid receptors. Comparison of these data to results when TMB or TMB-M were given i.v. suggests that these agents also have peripheral actions to affect gastrointestinal motility at sites outside the gastrointestinal tract.
Animals↗
Biological monitoring for trimethylbenzene exposure: a human volunteer study and a practical example in the workplace.
This paper presents data from both a human volunteer study looking at exposure to 1,3,5-trimethylbenzene (TMB) and an occupational hygiene study of a printing firm using screen wash containing technical grade TMB. The biomarkers measured were TMB in blood and breath, and urinary dimethylbenzoic acids (DMBAs). The volunteer (N = 4) study showed that TMB was rapidly absorbed into the bloodstream reaching a mean level of 0.85 micromol l(-1) during a 4 h exposure to 25 p.p.m. TMB. There was little decline 1 h post-exposure possibly indicating storage of TMB in adipose tissue. Breath TMB levels peaked within an hour of exposure commencing and averaged 137 nmol l(-1) during exposure. Elimination of TMB in breath was biphasic with an initial half-life of 60 min. Peak excretion of urinary DMBA occurred 4-8 h after the end of exposure and averaged 40 mmol mol(-1) creatinine. Elimination of DMBA in urine was biphasic with half-lives of 13 and 60 h indicating that accumulation of body burden throughout the working week is likely if exposure is repeated. The occupational hygiene study demonstrated an excellent correlation between personal air TMB levels and post-shift urinary DMBA levels (r = 0.997) collected on the third working day. The regression equation from this study indicates that 8 h exposure to 25 p.p.m. TMB would result in a urinary DMBA level of 206 mmol mol(-1) creatinine. All workers showed pre-shift levels of DMBA from exposure to TMB on previous days. Both urinary DMBA and breath TMB levels can be used as biomarkers of TMB exposure. Urine samples should be taken post-shift towards the end of the working week as significant body burden accumulation throughout the working week can be expected. Breath sampling is more suited to task or single-shift monitoring.
9,10-Dimethyl-1,2-benzanthracene↗
Beneficial effect of trimebutine and N-monodesmethyl trimebutine on trinitrobenzene sulfonic acid-induced colitis in rats.
The use of local anesthetics, such as lidocaine, has been proposed in the treatment of distal ulcerative colitis. Trimebutine maleate (TMB) displays a local anesthetic activity higher than that of lidocaine in rabbit corneal reflex. TMB and nor-TMB its main metabolite in human show similar affinity to that of bupivacaine toward sodium channel labeled by [3H]batrachotoxin and block sodium currents in sensory neurons from rat dorsal root ganglia. The aim of this study was to evaluate the effects of TMB and nor-TMB in comparison to lidocaine and bupivacaine in a rat model of acute colonic inflammation induced by trinitrobenzene sulfonic acid (TNBS). A single intracolonic instillation of TNBS (50 mg/kg dissolved in ethanol 30%) led to early plasma extravasation then macroscopic damage (hyperemia and necrosis), increased colonic weight and tissular MPO, a marker of neutrophilic infiltration. Local administration of TMB at dose of 3 to 60 mg/kg, 30 min before, 24 and 48 h after colitis induction, significantly reduced the severity of colitis. Nor-TMB (1, 3, 10, 30 mg/kg) as well as lidocaine (1, 3, 10 mg/kg) dose-dependently reduced colitis while bupivacaine at 10 mg/kg did not affect it significantly. In contrast systemic administration of TMB, nor-TMB and lidocaine at 10 mg/kg had no significant effect. Furthermore, local administration of TMB (30 mg/kg) and lidocaine (10 mg/kg) significantly reduced plasmatic extravasation. In conclusion, intracolonic treatment with TMB and nor-TMB improved acute experimental TNBS-induced colitis in rat and these effects could be explained by their local anesthetic activity.
Administration, Rectal↗
Pharmacological properties of trimebutine and N-monodesmethyltrimebutine.
Trimebutine [2-dimethylamino-2-phenylbutyl-3,4,5-trimethoxybenzoate hydrogen maleate (TMB)] has been demonstrated to be active for relieving abdominal pain in humans. To better understand its mechanism of action, we have tested TMB; nor-TMB, its main metabolite in humans; and their respective stereoisomers for their affinity toward sodium channels labeled by [3H]batrachotoxin, their effect on sodium, potassium, and calcium currents in rat dorsal root ganglia neurons, and their effect on veratridine-induced glutamate release from rat spinal cord slices. TMB has also been tested in an animal model of local anesthesia. TMB (Ki = 2.66 +/- 0.15 microM) and nor-TMB (Ki = 0.73 +/- 0.02 microM) displaced [3H]batrachotoxin from its binding site with affinities similar to that of bupivacaine (Ki = 7.1 +/- 0.9 microM). nor-TMB was found to block veratridine-induced glutamate release with an IC50 value of 8.5 microM, which is very similar to that of bupivacaine (IC50 = 8.2 microM); the effect of TMB was limited to 50% inhibition at 100 microM. TMB and nor-TMB blocked sodium currents in sensory neurons from rat dorsal root ganglia (IC50 = 0.83 +/- 0.09 and 1.23 +/- 0.19 microM, respectively), whereas no effect was observed on calcium currents at the same concentrations. A limited effect was observed on potassium currents (IC50 = 23 +/- 6 at 10 microM) for TMB. In vivo, when tested in the rabbit corneal reflex, TMB displayed a local anesthetic activity 17-fold more potent than that of lidocaine.
Animals↗
Transient monocular blindness and antiphospholipid antibodies in systemic lupus erythematosus.
BACKGROUND AND OBJECTIVE: Among patients with systemic lupus erythematosus (SLE), the presence of antiphospholipid antibodies (APA), notably the lupus anticoagulant, and anticardiolipin antibodies (aCL) characterizes a subset of patients with a thrombotic tendency. During the regular follow-up care of patients with SLE, we noticed that many described transient visual disturbances. Because a hypercoagulable state may cause transient monocular blindness (TMB), we determined the frequency of TMB and studied its relation to the presence of APA in patients with SLE. METHODS: We asked 175 unselected patients with SLE whether they had transient visual disturbances and reviewed their medical charts. All patients were examined with specific attention to the presence of livedo reticularis. Blood was examined for APA. RESULTS: Visual disturbances were recorded for 136 (78%) patients. According to predefined criteria, the symptoms were diagnosed as TMB for 10 (6%) patients and as visual disturbances associated with migraine for 18 (10%) patients. Five of the 10 patients with TMB had attacks in either eye. The 175 patients with SLE accrued a maximum total of 6,349 patient years in their lifetime. From this, the incidence of TMB can be calculated to be at least 158 per 100,000 per year. Lupus anticoagulant was detected in 3 of 10 patients with TMB and 41 of 165 patients without TMB (odds ratio, 1.3; 95% CI, 0.2 to 6.0). aCLs were found in 5 of 10 patients with TMB and 91 of 165 patients without TMB (odds ratio, 0.8; 95% CI, 0.2 to 3.7). CONCLUSIONS: The frequency of TMB among patients with SLE is at least 158 per 100,000 compared with the normal population (14 per 100,000 per year). However, among patients with SLE, no significant relation could be shown between TMB and the presence of APA or livedo reticularis.
Acute Disease↗
Actions of 8-(N,N-diethylamino)-n-octyl-3,4,5-trimethoxybenzoate in vascular smooth muscle cell cultures.
AIM: To study the effects of 8-(N,N-diethylamino)-n-octyl-3,4,5-trimethoxybenzoate (TMB-8) on vascular smooth muscle (VSM) cells A7r5. METHODS: The effects of TMB-8 were investigated in A7r5 cell cultures with 45CaCl2. RESULTS: TMB-8 reduced the intracellular free Ca2+ concentration, [Ca2+]i in a Ca(2+)-free medium and blocked Ca2+ entry from the extracellular site in a regular Ca2+ medium. The equilibrated total cellular binding of Ca2+ was increased by TMB-8 whereas 45Ca2+ entry activated by both NE and KCl was inhibited. However, the NE-activated Ca2+ entry was not blocked by TMB-8 if TMB-8 was added together with 45Ca2+ at a later time instead of by pretreatment. Similar to actions of NE and KCl, depletion of Ca2+ from sarcoplasmic reticulum (SR) would also activate Ca2+ entry, which was blocked by TMB-8. When TMB-8 was rinsed out alone or together with NE after pretreatment with NE plus TMB-8 in VSM cells, the inhibitory effect of TMB-8 was not affected. CONCLUSION: TMB-8 not only blocks Ca2+ entry from the extracellular site, but also enhances Ca2+ uptake into SR which, indirectly inhibits Ca2+ entry from the extracellular site.
Animals↗
[Ferritin--a biocatalyst of aromatic amine oxidation].
The tetramethylbenzidine (TMB) oxidation kinetics dependent on spleen ferritin (FERR) has been studied in TMB-FERR-H2O2 (1) and TMB-FERR-O2 (2) systems at pH 4.2 and 6.0. At TMB concentrations below 6 mM, the dependencies of the initial rate for protein oxidation in system (1) on initial concentrations of TMB and H2O2 are described by the Michaelis-Menten kinetics. In terms of (kcat/K(m)), the maximum FERR efficiency during TMB oxidation is equal to 2.8-10(-1) s-1. Mannitol, urea, ethanol and sodium fluoride strongly inhibit TMB oxidation in system (1). Competitive type oxidation inhibition by urea is characterized by K(i) = 12.5 mM. At TMB concentrations above 6 mM in system (2) the autocatalytic oxidation of the amine is observed. In both systems the initial rate of TMB oxidation increases strongly with a decrease in pH from 9.3 down to 4.2. In system (1) the initiating role is played by Fe3+ ions interaction with H2O2, that in system (2)-by the interaction of the same ions with the amine proper. In both cases, TMB oxidation is a catalytic chain process including elementary ion radical stages. The main oxidizing agents in system (2) are HO radicals and Fe3+ ions. The TMB interaction with FERR may be the reason for the lipid peroxidation increase following administration of aromatic amines.
Animals↗
Urinary excretion of dimethylhippuric acids in humans after exposure to trimethylbenzenes.
The aim of this study was to determine the urinary excretion of dimethylhippuric acids (DMHAs) in humans after experimental chamber exposure to trimethylbenzene (TMB) vapor. The DMHAs have been put forward as suitable biomarkers of exposure to products containing TMBs such as white spirit and petrol. Ten healthy male volunteers were exposed to TMB vapor in an exposure chamber for 2 h at a work load of 50 W. The subjects were exposed on four occasions, to 25 ppm of 1,2,4-TMB, 1,2,3-TMB, and 1,3,5-TMB, respectively, and 2 ppm of 1,2,4-TMB. Urine was collected from the onset of exposure until the following morning. All six possible DMHA isomers were analyzed by high-performance liquid chromatography. About 22% of the inhaled amount of 1,2,4-TMB was excreted as DMHAs within 24 h, mainly as 3,4-DMHA. The 24-h recovery of 1,2,3-TMB as DMHAs was 11%. Only 3% of the absorbed amount of 1,3,5-TMB was excreted as 3,5,-DMHA. The half-times of the different DMHA isomers ranged from 4 to 16 h. In addition to analysis of DMHAs, the excretion of unconjugated dimethylbenzoic acids in urine was estimated to account for approximately 3% of the dose of all TMBs. In conclusion, the urinary excretion of DMHA isomers may serve as a good indicator of TMB exposure. In this controlled short-term-exposure study the sum of excretion rate of several DMHA isomers reflected exposure more closely than did the excretion rate of any single DMHA.
Adult↗
Comprehensive genomic profiling and tumor mutational burden in parathyroid carcinoma: a nationwide real-world study from Japan.
PURPOSE: Parathyroid carcinoma (PC) is an extremely rare endocrine malignancy with limited treatment options for unresectable or recurrent cases. With the increasing use of comprehensive genomic profiling (CGP), treatment based on genomic findings is becoming more common. However, the frequency and clinical significance of elevated tumor mutational burden (TMB) in PC remain unclear because previous studies have been limited by small sample sizes. METHODS: We retrospectively analyzed genomic and clinical data of patients with PC registered in the Center for Cancer Genomics and Advanced Therapeutics database in Japan between June 2019 and March 2025. TMB values were obtained as reported by each CGP assay. TMB-H was defined as TMB ≥ 10 mut/Mb for descriptive analyses. We also assessed genomic alterations, microsatellite instability (MSI) status, and clinicogenomic characteristics. RESULTS: Twenty-five patients with PC were included. The median assay-reported TMB was 4.0 mut/Mb (range, 0-35). Seven tumors (28.0%) had assay-reported TMB values of ≥ 10 mut/Mb, including three (12.0%) with TMB ≥ 20 mut/Mb. The most frequently altered genes were CDC73 (40%), TP53 (32%), and MEN1 (24%). No co-alterations were observed between CDC73 and MEN1 or between CDC73 and TP53. One tumor was MSI-high and was included in the TMB-H group. POLE alterations were detected in three cases, including two tumors in the TMB-H group. CONCLUSION: This nationwide, real-world study demonstrated that a subset of PCs showed elevated assay-reported TMB values and genomic features potentially related to abnormalities in DNA replication or repair pathways. These findings support the clinical relevance of comprehensive genomic profiling in identifying the molecular heterogeneity and potential therapeutic opportunities for this rare malignancy.
Humans↗
Genotoxicity evaluation of trimethylbenzenes.
The three trimethyl isomers of benzene (hemimellitene, 1,2,3-TMB; pseudocumene, 1,2,4-TMB and mesitylene, 1,3,5-TMB) were investigated for different genotoxicity endpoints: in vitro, in the Ames test with Salmonella typhimurium TA97a, TA98, TA100 and TA102 strains in the presence and absence of rat liver S9 metabolic activation; in vivo, in the micronucleus and sister chromatid exchange (SCE) tests with bone marrow cells of Imp:Balb/c mice. Only the isomer of benzene with the methyl-group at position 1, 2, 3 was found to have mutagenic effect on S. typhimurium cells. Increase in bacterial reversions was observed in four conventional strains used in this study, but most clearly in TA97a. The mutagenic responses of 1,2,3-TMB with the SalmonellaL tester strains were observed in the experiments performed in the absence of enzymatic activation. None of the compounds had an influence on the frequency of micronucleated polychromatic erythrocytes in bone marrow cells of mice. However, all the three compounds were observed to have a cytogenetic potential of increasing the SCE level in these cells. Significant responses in SCE induction, compared with the level of those changes in corresponding solvent-administered controls, were obtained at three test doses of 1,2,3-TMB (730, 1470, 2200 mg/kg) and 1,2,4-TMB (900, 1800, 2700 mg/kg) and at two doses of 1,3,5-TMB (1800, 2700 mg/kg). These data provided a limited evidence for the genotoxic activity of 1,2,3-TMB and inadequate evidence for genotoxic activity of 1,2,4-TMB and 1,3,5-TMB.
Animals↗
Prevention and reduction of neural damage in ischemic strokes by w-(N,N'-diethylamino)-n-alkyl-3,4,5-trimethoxybenzoate compounds.
Experimental ischemic stroke was induced by an occlusion of middle cerebral artery and common carotid artery of rats for 60 min. The occlusion was then released and the extent of neural damage was measured by the estimation of necrosis areas where the dead neurons lost their ability to take up triphenyl tetrazolium chloride. w-(N,N'-Diethylamino)-n-alkyl-3,4,5-trimethoxybenzoate (TMB) compounds are calcium antagonists capable of reducing intracellular free calcium through inhibition of calcium release from the sarcoplasmic reticulum. These compounds were found to prevent and/or reduce neural damage effectively. When the animals were pretreated with TMB-2, TMB-5 and TMB-8, 1 hr before ischemia, the areas of neural necrosis were reduced almost completely by 95%, 99% and 92%, respectively. When these TMB compounds were given at 0 time and 1 hr after ischemia, the prevention of necrosis was almost complete also. However, when TMB-2, TMB-5 and TMB-8 were administered 6 hr after ischemia, the necrosis areas were reduced less effectively by 83%, 78% and 91%, respectively. TMB compounds were also found to increase cAMP and to reduce intracellular free calcium concentration. These results indicate that TMB compounds are effective calcium antagonists to prevent/treat ischemic stroke by reducing the intracellular free calcium through reduction of calcium release from sarcoplasmic reticulum.
Animals↗
Modification of valinomycin-mediated bilayer membrane conductance by 4,5,6,7-tetrachloro-2-methylbenzimidazole.
The compound 4,5,6,7-tetrachloro-2-methylbenzimidazole (TMB), has been found to markedly modify the steady-state valinomycin-mediated conductance of potassium (K+) ions through lipid bilayer membranes. TMB alone does not contribute significantly to membrane conductance, being electrically neutral in solution. In one of two classes of experiments (I), valinomycin is first added to the aqueous phases, then changes of membrane conductance accompanying stepwise addition of TMB to the water are measured. In a second class of experiments (II), valinomycin is added to the membrane-forming solution, followed by TMB additions to the surrounding water. In both cases membrane conductance shows an initial increase with increasing TMB concentration which is more pronounced at lower K+ ion concentration. At TMB concentrations in excess of 10(-5) M, membrane conductance becomes independent of K+ ion concentration, in contrast to the linear dependence observed at TMB concentrations below 10(-7) M. This transition is accompanied by a change of high field current-voltage characteristics from superlinear (or weakly sublinear) to a strongly sublinear form. All of these observations may be correlated by the kinetic model for carrier-mediated transport proposed by Läuger and Stark (Biochim. Biophys. Acta 211:458, 1970) from which it may be concluded that valinomycin-mediated ion transport is limited by back diffusion of the uncomplexed carrier at high TMB concentrations. Experiments of class I reveal a sharp drop of conductance at high (greater than 10(-5) M) TMB concentration, not seen in class II experiments, which is attributed to blocked entry of uncomplexed carrier from the aqueous phases. Valinomycin initially in the membrane is removed by lateral diffusion to the surrounding torus. The time dependence of this removal has been studied in a separate series of experiments, leading to a measured coefficient of lateral diffusion for valinomycin of 5 x 10(-6) cm2/sec at 25 degrees C. This value is about two orders of magnitude larger than the corresponding coefficient for transmembrane carrier diffusion, and provides further evidence for localization of valinomycin in the membrane/solution interfaces.
Benzimidazoles↗
Inhalation toxicokinetics of 1,2,4-trimethylbenzene in volunteers: comparison between exposure to white spirit and 1,2,4-trimethylbenzene alone.
The objective of this study was to compare the toxicokinetics of inhaled 1,2,4-trimethylbenzene (1,2,4-TMB) in man after exposure to white spirit with that observed after exposure to 1,2,4-TMB alone. TMBs occur mainly in petroleum products and the TMBs or their metabolites have been suggested as suitable biomarkers of exposure to white spirit and other distillation products. The toxicokinetics were studied in 9 male, healthy volunteers exposed to solvent vapours in an exposure chamber for 2 h during a work load of 50 W. The subjects were exposed to 11 mg/m3 of 1,2,4-TMB on two occasions; during exposure to 1,2,4-TMB vapour alone and during exposure to 300 mg/m3 of white spirit. The 1,2,4-TMB isomer was analyzed in blood and exhaled air by gas chromatography. In addition, a major urinary metabolite of 1,2,4-TMB, 3,4-dimethylhippuric acid (3,4-DMHA), was analyzed by high performance liquid chromatography. Further the occurrence of acute effects was studied by means of a questionnaire. Irritation and central nervous system symptoms were recorded by ratings on a 100-mm visual analogue scale. Blood levels of 1,2,4-TMB and excretion rates of 3,4-DMHA in urine were markedly elevated both during and after exposure to white spirit as compared to exposure to TMB alone. Thus, it appears that components in white spirit inhibit the metabolic elimination of 1,2,4-TMB. This should be considered in biological exposure monitoring as well as in risk assessment. No irritation or central nervous system effects were reported at these conditions.
Administration, Inhalation↗
Peroxidase-catalyzed co-oxidation of 3,3',5,5'-tetramethylbenzidine with 2-amino-4-nitrophenol, 4,4'-dihydroxydiphenylsulfone, and their polydisulfides in aqueous and micellar media.
The effects of different concentrations of 2-amino-4-nitrophenol (ANP) and of its polydisulfide (poly(ADSNP)) on peroxidase-catalyzed oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) were studied at 20 degrees C in reversed micelles of AOT (0.2 M) in heptane and in mixed reversed micelles of AOT (0.1 M)-Triton X-100 (0.1 M) in isooctane supplemented with 15% hexanol. The oxidation of TMB was activated nearly twofold in the presence of ANP and nearly fourfold in the presence of poly(ADSNP) in reversed micelles of AOT, whereas in the mixed micelles oxidation of the TMB-ANP pair was associated with inhibition of TMB conversion and poly(ADSNP) activated oxidation of TMB. The co-oxidation of TMB with 4,4'-dihydroxydiphenylsulfone (DDS) and with its polydisulfide (poly(DSDDS)) at different concentrations of phenol components was accompanied by activation of TMB conversion in 0.01 M phosphate buffer (pH 6.4) supplemented with 5% DMF and in reversed micelles of AOT in heptane. The effect of pH of the aqueous solution on the initial oxidation rate of the TMB-DDS and TMB-poly(DSDDS) pairs and also the effect of hydration degree of reversed micelles of AOT on conversion of the same pairs by peroxidase were studied. A scheme of peroxidase-dependent co-oxidation of "aromatic amine-phenol" pairs is proposed and discussed. A significant part of this scheme is a nonenzymatic exchange of phenoxyl radicals with amines and of aminyl radicals with phenols.
Benzidines↗