Biomedical subjects

G Brambilla

Publications and source records attributed to G Brambilla.

At least 37 records · Page 2Linked to original sources

PubMed2001

Determination of flumethasone in calf urine and serum by liquid chromatography-tandem mass spectrometry.

Corticosteroids can be illegally administered to cattle as growth promoting agents to improve meat production. We developed a liquid chromatography-atmospheric pressure ionization mass spectrometry-mass spectrometry (LC-MS-MS) method able to identify and quantify flumethasone, one of the most potent fluorinated synthetic corticosteroid, in serum and urine from treated calves. The analyte was purified from urine (conjugated and free, following enzymatic hydrolysis) and from serum by C18 solid-phase and liquid-liquid extractions, then analyzed by LC-MS-MS monitoring the product ions of an abundant precursor (SRM in negative ionization mode). Results on flumethasone residues in biological fluids in three calves treated at different levels are presented. This method allowed the detection of flumethasone in bovine urine and serum at the 30-pg/ml level.

Animal Husbandry↗

PubMed2001

Determination of monobromobimane derivatives of phenylmercapturic and benzylmercapturic acids in urine by high-performance liquid chromatography and fluorimetry.

A method was developed for the determination in human urine of S-phenylmercapturic (PMA) and S-benzylmercapturic (BMA) acids, metabolites respectively of benzene and toluene. PMA and BMA were determined, after alkaline hydrolysis, to give respectively thiophenol and benzylmercaptan, and coupling of the thiol-containing compounds with monobromobimane (MB), by reversed-phase HPLC on a diphenyl-silica bonded cartridge (100 x 4.6 mm I.D., 5 microm particle size) with fluorimetric detection. Wavelengths for excitation and emission were 375 and 480 nm, respectively. The recovery of PMA and BMA from spiked urines was >90% in the 10-500 microg/l range; the quantification limits were respectively 1 and 0.5 microg/l; day-to-day precision at 42 microg/l was C.V. <7%. The suitability of the proposed procedure for the biological monitoring of exposure to low-level airborne concentrations of benzene and toluene, was evaluated by analyzing the urinary excretion of PMA and BMA in subjects exposed to different sources of aromatic hydrocarbons, namely occupationally-unexposed referents (non-smokers, n=15; moderate smokers, n=8; mean number of cigarettes smoked per-day=17 cig/day) and non-smoker workers occupationally exposed to toluene in maintenance operations of rotogravure machines (non-smokers, n=17). Among referents, non-smokers showed values of PMA ranging from <1 to 4.6 microg/l and BMA from 1.0 to 10.4 microg/l; in smokers, PMA values ranging from 1.2 to 6.7 microg/l and BMA from 9.3 to 39.9 microg/l, were observed. In occupationally exposed non-smoker subjects, BMA median excretion value (23.6 microg/l) was higher than in non-smoker referents (3.5 microg/l) (P<0.001) and individual BMA values (y, microg/l) were associated and increased with airborne toluene concentration (x, mg/m3) according to the equation y=6.5+0.65x (r=0.69, P<0.01, n=17). The proposed analytical method appears to be a sensitive and specific tool for biological monitoring of low-level exposure to benzene and toluene mixtures in occupational and environmental toxicology laboratory.

Acetylcysteine↗

PubMed2001

Effects of mono-, di- and tri-hydroxybenzoic acids on the nitrosation of propranolol: structure-activity relationship.

Nitrosation of propranolol under standard conditions recommended by the World Health Organization (10mM propranolol hydrochloridre, 40mM sodium nitrite, pH 3.5) was performed in the absence and in the presence of benzoic acid and of twelve mono-, di- and tri-hydroxybenzoic acids, added to the nitrosation mixture in concentrations ranging from 2 to 40mM, in order to examine their effect on the nitrosation reaction. The yield of N-nitrosopropranol (NOP) was reduced by benzoic acid and, with potency decreasing in the following order, by 2,3,4-tri-hydroxybenzoic acid>/=3,4-tri-hydroxybenzoic acid>2,5-di-hydroxybenzoic acid>2,3-di-hydroxybenzoic acid>3-hydroxybenzoic acid>2-hydroxybenzoic acid>3,4,5-tri-hydroxybenzoic acid>4-hydroxybenzoic acid; their inhibiting effect was concentration-dependent. In contrast, 2,4-di-hydroxybenzoic acid, 2,6-di-hydroxybenzoic acid and 2,4,6-tri-hydroxybenzoic acid caused an increase in the yield of NOP that was inversely related to their concentration. 3,5-Di-hydroxybenzoic acid was substantially inactive. These findings indicate that, depending on the positions of carboxyl group and hydroxyl groups on the benzene ring, mono-, di- and tri-hydroxybenzoic acids may inhibit or hasten nitrosation reactions. As compared with benzenediols and benzenetriols [Mutat. Res. 398 (1998) 75], hydroxybenzoic acids inhibit the nitrosation of propranolol to a greater extent and have the advantage of being nonmutagenic and less toxic.

Area Under Curve↗

PubMed2001

Evaluation of the oxidative stress in growing pigs by microplate assays.

The ability of pigs to neutralize the reactive oxygen species (ROS) plays a key role in their welfare. Two micromethods were developed to evaluate the oxidative stress and the anti-oxidative response in sera. We tested these methods for linearity, repeatability and reproducibility. A hydroxyl radicals (HR) test, based on the Fenton reaction, showed a linearity between 0.26 and 4.5 mM H2O2 (r = 0.997), with a coefficient of repeatability (CVr) of 1.9 and a coefficient of reproducibility (CVR) of 2.9. An anti-oxidant power (AOP) test, based on the capability of sera to neutralize a titred hypochlorous acid solution (HClO), showed a linearity between 55 and 880 microM HClO neutralized (r = 0.984), with CVr = 3.1 and CVR = 4.9. We assessed the applicability of such tests in field conditions on three different farms. Farm A recorded a positive anamnesis of Mulberry heart disease. Dietary Vitamin E supplementation was given at 50 p.p.m. in farms A and B and at 150 p.p.m. in farm C, respectively. The group from farm A showed HR sera levels higher than those of farm B and farm C (farm A, mean = 31.61 +/- 2.87 mM H2O2, n = 10; farm B, 28.53 +/- 2.30, n = 10; and farm C, 25.63 +/- 1.03, n = 10; P < 0.01). The AOP test was not able to discriminate between farms. The AOP levels found (mean = 472.50 microM HClO neutralized: n = 30) probably represent the maximum response of the organism to compensate the oxidative stress. HR and AOP are stable in sera stored at +4 degrees C. We discuss the application of such methods for the assessment of farmed animals' welfare.

Animals↗

PubMed2001

Measurement techniques for transport noise.

The noise front transport systems (roads, railways and aircraft) are increasing more and more both in space and in time and, therefore, they are still the major factor responsible for environmental noise pollution. The population exposed to transport noise is also increasing. and the corresponding health effects on people (i.e. annoyance and sleep disturbance) become more severe. Due to this current situation international and national legislation has been issued and implemented to reduce the harmful effects of such noise. This paper describes the techniques prescribed by recent Italian legislation to measure road, railway and aircraft noise.

Aircraft↗

PubMed2000

Comparison of micronuclei frequencies in mono-, bi- and poly-nucleated lymphocytes from subjects of a residential suburb and subjects living near a metallurgical plant.

Spontaneous baseline frequencies of micronuclei in mono-, bi- and poly-nucleated lymphocytes were analyzed, using the cytokinesis-block technique, in 103 subjects living in a residential suburb (Genova-Nervi), and in 203 subjects living in an urban industrialized area near a metallurgical plant and a coke factory (Genova-Cornigliano). Statistical analysis showed that the average frequency of micronucleated binucleated lymphocytes (MnBNL) was significantly higher (1.42-fold) in donors of Nervi than in donors of Cornigliano living in a contaminated environment. In contrast, the average frequency of micronucleated polynucleated lymphocytes (MnPNL) was significantly higher (1.66-fold) in donors of Cornigliano than in donors of Nervi. The existence in the whole population examined of a positive correlation between frequency of MnBNL and frequency of MnPNL and the absence of a positive correlation between frequency of bi- and poly-nucleated lymphocytes and frequency of MnPNL suggest that the formation of MnPNL is a consequence of genetic damage and not of mitotic errors arising during the division of bi- and poly-nucleated cells. In agreement with previous findings the frequency of MnBNL increased with age and was significantly higher in females than in males; unexpectedly it was higher in non-smokers/non-drinkers than in smokers/drinkers.

Environmental Exposure↗

PubMed2000

Clinical and pharmacological profile in a clenbuterol epidemic poisoning of contaminated beef meat in Italy.

Long-acting beta adrenergic agonists, such as clenbuterol accumulate in the liver, but not meat of treated farm animals, and result in epidemic poisonings in consumers. We describe an outbreak of poisoning in 15 people, following the consumption of meat. Clinical symptoms (distal tremors, palpitations, headache, tachipnoea-dyspnoea, and also moderate hyperglycaemia, hypokalemia and leucocytosis) were seen in nine hospitalised patients, starting about 0.5-3 h after poisoning, and disappearing within 3-5 days later. Clenbuterol was found in the urine of all the symptomatic patients, at higher levels than pharmacokinetic computing (mean level 28 ng/ml, 36 h after ingestion), based on the levels found in the meat (1140-1480 ng/g edible tissue). Thus, epidemic poisoning can be produced following the consumption of contaminated meat. The need for a better definition of pharmaco- and toxico-kinetics, not only for drugs ingested as parent drug, but also when ingested as residues with animal tissues, is recommended.

Adrenergic beta-Agonists↗

PubMed2000

Comparison between blood and urinary toluene as biomarkers of exposure to toluene.

OBJECTIVES: To compare blood toluene (TOL-B) and urinary toluene (TOL-U) as biomarkers of occupational exposure to toluene, and to set a suitable procedure for collection and handling of specimens. METHOD: An assay based on headspace solid-phase microextraction (SPME) was used both for the determination of toluene urine/air partition coefficient (lambdaurine/air) and for the biological monitoring of exposure to toluene in 31 workers (group A) and in 116 non-occupationally exposed subjects (group B). Environmental toluene (TOL-A) was sampled during the work shift (group A) or during the 24 h before specimen collection (group B). Blood and urine specimens were collected at the end of the shift (group A) or in the morning (group B) and toluene was measured. RESULTS: Toluene lambdaurine/air was 3.3 +/- 0.9. Based on the specimen/air partition coefficient, it was calculated that the vial in which the sample is collected had to be filled up to 85% of its volume with urine and 50% with blood in order to limit the loss of toluene in the air above the specimen to less than 5%. Environmental and biological monitoring of workers showed that the median personal exposure to toluene (TOL-A) during the work-shift was 80 mg/m3, the corresponding TOL-B was 82 microg/l and TOL-U was 13 microg/l. Personal exposure to toluene in environmentally exposed subjects was 0.05 mg/m3, TOL-B was 0.36 microg/l and TOL-U was 0.20 microg/l. A significant correlation (P < 0.05) was observed between TOL-B or TOL-U and TOL-A (Pearson's r = 0.782 and 0.754) in workers, but not in controls. A significant correlation was found between TOL-U and TOL-B both in workers and in controls (r = 0.845 and 0.681). CONCLUSION: The comparative evaluation of TOL-B and TOL-U showed that they can be considered to be equivalent biomarkers as regards their capacity to distinguish workers and controls and to correlate with exposure. However, considering that TOL-U does not require an invasive specimen collection, it appears to be a more convenient tool for the biological monitoring of exposure to toluene.

Adult↗

PubMed2000

DNA damage induced by 3,3'-dimethoxybenzidine in liver and urinary bladder cells of rats and humans.

3,3'-Dimethoxybenzidine (DMB), a congener of benzidine used in the dye industry and previously found to be carcinogenic in rats, was evaluated for its genotoxic activity in primary cultures of rat and human hepatocytes and of cells from human urinary bladder mucosa, as well as in liver and bladder mucosa of intact rats. A similar modest dose-dependent frequency of DNA fragmentation was revealed by the alkaline elution technique in metabolically competent primary cultures of both rat and human hepatocytes exposed for 20 h to subtoxic DMB concentrations ranging from 56 to 180 microM. Replicating rat hepatocytes displayed a modest increase in the frequency of micronucleated cells after a 48-h exposure to 100 and 180 microM concentrations. In primary cultures of human urinary bladder mucosa cells exposed for 20 h to 100 and 180 microM DMB, the Comet assay revealed a clear-cut increase of DNA fragmentation. In rats given one-half LD50 of DMB as a single oral dose, the GSH level was reduced in both the liver and urinary bladder mucosa, whereas DNA fragmentation was detected only in the bladder mucosa. Taken as a whole, these results suggest that DMB should be considered a potentially genotoxic chemical in both rats and humans; the selective effect on the rat urinary bladder might be the consequence of pharmacokinetic behavior.

Administration, Oral↗

PubMed1999

Correlation between induction of DNA fragmentation and micronuclei formation in kidney cells from rats and humans and tissue-specific carcinogenic activity.

Five chemicals, known to induce kidney tumors in rats, were assayed for their ability to induce DNA damage and formation of micronuclei in primary cultures of rat and human kidney cells and in the kidney of intact rats. Significant dose-dependent increases of DNA fragmentation, as measured by the Comet assay, and of micronuclei frequency were obtained in primary kidney cells from both rats and humans with the following concentrations of the five test compounds: lead acetate (not tested for micronuclei induction) and potassium bromate from 0.56 to 1.8 mM, phenacetin from 1 to 3.2 mM, and 1, 4-dichlorobenzene and nitrilotriacetic acid from 1.8 to 5.6 mM. In terms of DNA-damaging potency all the five chemicals were more active in rat than in human kidney cells, whereas the potencies in inducing micronuclei formation were similar in the two species with the exception of 1,4-dichlorobenzene, which was slightly more potent in human than in rat cells. Consistently with the results observed in vitro, statistically significant increases in the average frequency of both DNA breaks and micronucleated cells were detected in the kidney of rats given po a single (12 LD50) or three successive daily doses (13 LD50) of the five test compounds. 4, 4'-Methylenedianiline, a carcinogen which does not induce kidney tumors in rats, gave negative responses in both in vitro and in vivo assays. These findings give evidence that kidney carcinogens may be identified by short-term genotoxicity assays using as target kidney cells and show that the five chemicals tested produce in primary cultures of kidney cells from human donors effects similar to those observed in rats.

Adult↗

PubMed1999

Modulation of aerosol clouds produced by pressurised inhalation aerosols.

The inclusion of non-volatile components such as glycerol or polyethylene glycol in hydrofluoralkane (HFA) solution formulations for pressurised metered dose inhalers (pMDIs), greatly increases the particle size of the aerosol. Cloud characteristics can be further modulated by permuting this factor with the choice of propellant and the dimensions of the actuator, to give a chosen fine particle dose and particle diameter. This principle has been used to design solutions which closely match the performance of chlorofluorocarbon based suspension formulations containing beclomethasone dipropionate, budesonide and ipratropium bromide as assessed for pharmaceutical equivalence using the Andersen Cascade impactor.

Aerosols↗

PubMed1999

Gas chromatography-electron-capture detection of urinary methylhippuric acid isomers as biomarkers of environmental exposure to xylene.

Methylhippuric acid isomers (MHAs), urinary metabolites of xylenes, were determined, after clean-up by C18-SPE and esterification with hexafluoroisopropanol and diisopropylcarbodiimide, by GC with ECD detection, on an SPB-35 capillary column (30 m, 0.32 mm I.D., 0.25 microm film thickness, beta = 320). S-benzyl-mercapturic acid was used for internal standardization. Chromatographic conditions were: oven temperature 162 degrees C, for 14.2 min; ramp by 30 degrees C/min to 190 degrees C, for 3.5 min; ramp by 30 degrees C/min to 250 degrees C, for 4 min; helium flow rate: 1.7 ml/min; detector and injector temperature: 300 degrees C. The sample (1 microl) was injected with a split injection technique (split ratio 5:1). MHA recovery was >95% in the 0.5-20 micromol/l range; the limit of detection was <0.25 micromol/l; day-to-day precision, at 2 micromol/l, was Cv<10%. Urinary MHAs were determined in subjects exposed to different low-level sources of xylenes: (a) tobacco smoking habit and (b) BTX urban air pollution (airborne xylene ranging from 0.1 to 3.7 micromol/m3). Study (a) showed a significant difference between urinary MHA median excretion values of nonsmokers and smokers (4.6 micromol/l vs. 8.1 micromol/l, p<0.001). Study (b) revealed a significant difference between indoor workers and outdoor workers (4.3 micromol/l vs. 6.9 micromol/l, p<0.001), and evidenced a relationship between MHAs (y, micromol/mmol creatinine) and airborne xylene (x, micromol/m3) (y = 0.085+0.34x; r = 0.82, p<0.001, n = 56). Proposed biomarkers could represent reliable tools to study very low-level exposure to aromatic hydrocarbons such as those observed in the urban pollution due to vehicular traffic or in indoor air quality evaluation.

Air Pollution↗

PubMed1999

Genotoxicity testing of potassium canrenoate in cultured rat and human cells.

Potassium canrenoate (PC), a competitive aldosterone antagonist used as a diuretic and in the treatment of hypertension, was examined for its capacity to produce genotoxic effects in cultured rat and human cells. At subtoxic concentrations (10-90 microM) PC was found to induce a dose-dependent degree of DNA fragmentation, as detected by the Comet assay, and of DNA repair synthesis, as measured by quantitative autoradiography, in primary cultures of hepatocytes from rat and human donors of both genders. In rat hepatocytes both DNA fragmentation and DNA repair were more marked after 3 h than after 20 h exposure and in cultures from females than from males. In human hepatocytes from one male and two female donors, PC caused a similar effect in terms of DNA fragmentation, whereas DNA repair was detected in cultures from only two of the same three donors and was less marked than in rat hepatocytes. A modest but statistically significant increase in micronucleated cells was present in primary cultures of replicating rat hepatocytes exposed to 10 or 30 microM PC for 48 h, the response being, in this case also, more evident in females than in males. In contrast, PC did not induce micronucleus formation in human hepatocytes from two female donors. Any evidence of DNA fragmentation and micronucleus formation was absent in cultured human lymphocytes. Taken as a whole these findings support the hypothesis that hepatocytes activate PC to DNA-damaging reactive species. PC induced the observed genotoxic effects at concentrations close to those produced in humans by the administration of therapeutic doses, but these effects were as a whole more marked in rat than in human hepatocytes. Since PC shares the 17-hydroxy-3-oxopregna-4,6-diene structure with cyproterone acetate, chlormadinone acetate and megestrol acetate, previously found to be genotoxic to both rat and human hepatocytes, the potential carcinogenic hazard of this type of steroids cannot be neglected.

Adult↗

PubMed1998

Induction of micronuclei and of enzyme-altered foci in the liver of female rats exposed to progesterone and three synthetic progestins.

Progesterone (PG) and three structurally similar synthetic progestins-norethisterone (NE), allylestrenol (AE), and dydrogesterone (DG)-have been compared for their ability to induce the formation of micronuclei and of enzyme-altered foci in the liver of female rats. In the micronucleus assay, carried out in rats given a single p.o. dose of 100 mg kg-1 3 days before partial hepatectomy and sacrificed for cell sampling 2 days later, the frequency of micronucleated hepatocytes was 3.5-fold higher than in controls with PG, 2.8-fold with DG, 2.2-fold with NE and 2.1-fold with AE, but the increase was statistically significant only for PG. In the liver foci assay, performed to evaluate the tumor initiating activity of p. o. dosing with 100 mg kg-1 once a week for 6 successive weeks, the values of the number and area of gamma-glutamyltranspeptidase-positive foci were, as compared to controls, 15.9- and 100-fold higher with NE, and 13.9- and 52-fold higher with AE, but only the increase of area produced by NE was statistically significant; PG and DG did not display in this test any activities. Considered together with previous findings, these results suggest that NE might be biotransformed in the liver into reactive species and thus behave as a weak genotoxic agent.

Allylestrenol↗

PubMed1998

Evaluation of omeprazole genotoxicity in a battery of in vitro and in vivo assays.

Omeprazole, a proton pump inhibitor of wide use in the treatment of gastric acid-related disorders, was evaluated for its genotoxic effects in both rat and human cultured cells and in the intact rat. DNA repair synthesis, as revealed by autoradiography, was detected in primary cultures of metabolically competent rat hepatocytes exposed to concentrations ranging from 10 to 100 mg/l, but the responses cannot be considered as clearly positive. Under the same experimental conditions any significant evidence of DNA repair was absent in primary hepatocytes from two human donors. At the same concentrations a modest but dose-related increase of micronucleated cells, that reached the level of statistical significance at 33 mg/l, was present in primary rat hepatocytes and in one of two human donors. In human lymphocytes exposed to subtoxic concentrations ranging from 0.78 to 12.5 mg/l a reproducible concentration dependent clastogenic effect was absent. In partially hepatectomized female rats treated with a single p.o. dose of 1000 mg/kg, the frequency of micronucleated cells was 5.2-fold higher than in controls in the liver, but only 2.0-fold higher in polychromatic erythrocytes of the bone marrow. In rats of the same sex given azoxymethane as initiator of colon carcinogenesis the oral administration for 8 successive weeks of 10 mg/kg omeprazole on alternate days increased the response to azoxymethane, as indicated by the occurrence in colon mucosa of a modest but statistically significant increase in both the average number and size of aberrant crypt foci. Taken as a whole, our results suggest that omeprazole behaves as a weak genotoxic agent for the rat liver. Reliable information about the potential genotoxic risk to humans requires further studies on primary cells from a wide number of donors.

Adult↗

PubMed1998

Enoxaparin plus compression stockings compared with compression stockings alone in the prevention of venous thromboembolism after elective neurosurgery.

BACKGROUND: Compression stockings are recommended for prophylaxis against venous thromboembolism in patients undergoing neurosurgery, but anticoagulant agents have not gained wide acceptance because of concern about intracranial bleeding. METHODS: In a multicenter, randomized, double-blind trial, we assessed the efficacy and safety of enoxaparin in conjunction with the use of compression stockings in the prevention of venous thromboembolism in patients undergoing elective neurosurgery. Enoxaparin (40 mg once daily) or placebo was given subcutaneously for not less than seven days beginning within 24 hours after the completion of surgery. The primary end point was symptomatic, objectively confirmed venous thromboembolism or deep-vein thrombosis assessed by bilateral venography, which was performed in all patients on day 8+/-1. Bleeding side effects were carefully assessed. RESULTS: Among the 307 patients assigned to treatment groups, 129 of the 154 patients receiving placebo (84 percent) and 130 of the 153 patients receiving enoxaparin (85 percent) had venographic studies adequate for analysis. An additional patient in the placebo group died before venography of autopsy-confirmed pulmonary embolism. In this analysis, 42 patients given placebo (32 percent) and 22 patients given enoxaparin (17 percent) had deep-vein thrombosis (relative risk in the enoxaparin group, 0.52; 95 percent confidence interval, 0.33 to 0.82; P=0.004). The rates of proximal deep-vein thrombosis were 13 percent in patients receiving placebo and 5 percent in patients receiving enoxaparin (relative risk in the enoxaparin group, 0.41; 95 percent confidence interval, 0.17 to 0.95; P=0.04). Two patients in the placebo group died of autopsy-confirmed pulmonary embolism on days 9 and 16. Major bleeding occurred in four patients receiving placebo (intracranial bleeding in all four) and four patients (intracranial bleeding in three) receiving enoxaparin (3 percent of each group). CONCLUSIONS: Enoxaparin combined with compression stockings is more effective than compression stockings alone for the prevention of venous thromboembolism after elective neurosurgery and does not cause excessive bleeding.

Adult↗

PubMed1998

Identification of main corticosteroids as illegal feed additives in milk replacers by liquid chromatography-atmospheric pressure chemical ionisation mass spectrometry.

Corticosteroids were proposed as growth promoting agents to improve commercial quality of meat. We developed a liquid chromatography-atmospheric pressure chemical ionisation mass spectrometry (LC-APCI-MS) method able to identify the presence in milk replacers, when given by mouth, of dexamethasone, betamethasone, flumethasone, triamcinolone, predinisotone, prednisolone, methylprednisolone, fludrocortisone and beclomethasone, at levels in the range of 20-100 ppb. C18 solid-phase extraction, LC-RP C8 column separation, data acquisition (positive ions) in the scan range m/z 200-550 allowed us to differentiate and identify compounds by protonated molecules, their methanolic adducts and fragmentation patterns.

Adrenal Cortex Hormones↗

PubMed1998

The effect of benzenediols and benzenetriols on the nitrosation of propranolol depends on the position of hydroxyl groups on the benzene ring.

Nitrosation of propranolol under the standard conditions recommended by the World Health Organization (10 mM propranolol hydrochloride, 40 mM sodium nitrite, pH 3.5) was carried out in the absence and in the presence of phenol, benzenediols and benzenetriols added to the nitrosation mixture in concentrations ranging from 2 to 40 mM. The yield of N-nitrosopropranolol (NOP) was reduced, with potency decreasing in the following order, by 1,2-benzenediol > 1,2,3-benzenetriol > 1,4-benzediol; their inhibiting effect was dose-dependent. 1,2,4-Benzenetriol displayed a significant inhibitory activity only at 20-40 mM concentrations. The maximum reduction of NOP formation (7% of the yield obtained under control conditions) was produced at 120 min by 40 mM 1,2-benzenediol. In contrast, the yield of NOP was increased by 1,3-benzenediol and 1,3,5-benzenetriol, but this effect was inversely related to the concentration. The effect of the various phenols on the time course of propranolol nitrosation was dependent on both the test phenol and its concentration. 1,2-Benzenediol and 1,3-benzenediol displayed on the nitrosation of proline effects qualitatively of the same type, but quantitatively different, as compared with those observed on the nitrosation of propranolol. Taken as a whole, the results of this study indicate that depending on the positions of hydroxyl groups on the benzene ring benzenediols and benzenetriols may inhibit or hasten nitrosation reactions.

Benzene Derivatives↗