Francesco Pasini

Breath and blood levels of benzene, toluene, cumene and styrene in non-occupational exposure

SummaryBenzene, toluene, cumene and styrene were measured in the breath and blood of two groups of individuals. The first group included individuals belonging to a hospital staff, the second group included chemical workers who were not exposed to the abovementioned chemicals. The chemical workers were examined in plant infirmaries on the morning before the start of the workshift, and the hospital staff in the hospital infirmaries. One environmental air sample was taken in the infirmaries for each individual at the moment of the biological samplings. The environmental concentrations of benzene and styrene were significantly higher in the infirmaries of the chemical plant than in the infirmaries of the hospital. On the other hand, the environmental concentrations of toluene and cumene were not significantly different in the plant infirmaries and in the hospital infirmaries. In the hospital staff the alveolar concentrations of benzene, toluene and styrene were significantly lower than those in the chemical workers. In the hospital staff the blood concentrations of benzene, toluene and styrene were not significantly different from those in the chemical workers. Only the blood cumene concentration was significantly higher in the chemical workers. In hospital staff, smokers showed alveolar and blood concentrations of benzene and toluene that were significantly higher than those measured in the non smoker hospital staff. With reference to chemical workers, only alveolar benzene concentration was significantly higher in smokers than in non smokers. A significant blood benzene difference was found between the non smoker hospital staff and the non smoker chemical workers. A correlation between alveolar and environmental concentrations was found for benzene, toluene and cumene, but not for styrene. In the two groups of individuals, correlations between blood and alveolar concentrations of the four compounds were also studied.

Ethylene oxide exposure

SummaryOccupational exposure to ethylene oxide (ETO) was studied in ten workers employed in a hospital sterilizer unit by testing environmental air, alveolar air and blood during and at the end of the workshift. Alveolar (Ca) and blood (Cb) ETO concentrations were correlated with each other (r = 0.744, na = 36, P < 0.001) and both with the environmental (Ci) concentrations (r = 0.947, n = 144, P < 0.001; r = 0.827, n = 36, P < 0.001). The alveolar retention of ETO (1-Ca/Ci) was equal to 75–80% of the inhaled ETO. In comparison with a blood/air partition coefficient equal in vitro to 90 (SD = 20), the mean Cb/Ca ratio found in the exposed workers was equal to 12–17. During work the blood ETO concentration was, on average, three times the environmental ETO concentration.

S-(acetamidomethyl)mercapturic acid (AMMA): A new biomarker for occupational exposure to N,N-dimethylacetamide

N,N-dimethylacetamide (DMA) is used in the textile and plastics industry as a solvent alternative to more toxic N,N-dimethylformamide. Here we studied toxicokinetics of two major urinary metabolites of DMA, namely, S-(acetamidomethyl)mercapturic acid (AMMA) and N-methylacetamide (NMA). Urine samples were collected from workers exposed to DMA in a factory manufacturing acrylic fibers. AMMA and NMA were determined by HPLC/MS and GC/MS, respectively. The working scheme in the factory consisted of periods of three consecutive working shifts alternated regularly with two days off work. In the first stage of the study, NMA and AMMA were determined in urine samples collected before, in the middle, and at the end of one working shift. In the second stage, urine was collected five times during three consecutive days after a two-day rest: before and at the end of the first and second working shifts and before the third shift. It was found that the end-of-shift NMA levels were several folds higher than the pre-shift levels of the same day and dropped significantly until the next shift. On the other hand, there were no significant differences in AMMA levels before and at the end of the same shift but a continuous rise during the three-day working period was observed. Median values of NMA concentrations at the end of working shifts were between 10.1 and 17.3 mg/g creatinine, median AMMA concentrations in the second or third day of the working period varied between 12.4 and 38.1 mg/g creatinine. The approximate half-lives of NMA and AMMA (means) in the exposed workers were about 9 and 29 h, respectively. Thus, while NMA in the end-of-shift urine samples remains a preferential biomarker of DMA exposure during that shift, AMMA determined at the end of a work-week reflects cumulative exposure over the last few days. Further studies are needed to determine AMMA concentrations corresponding to the threshold limit value of DMA.

11β-hydroxysteroid dehydrogenase type 2 polymorphisms and activity in a Chilean essential hypertensive and normotensive cohort.

BACKGROUND 11β-hydroxysteroid dehydrogenase type 2 enzyme (11β-HSD2) inactivates cortisol (F) to cortisone (E); its impairment is associated with hypertension. We reported that 15.7% of the Chilean essential hypertensives possessed a high F/E ratio suggesting a partial deficit in 11β-HSD2 activity. It has been reported that the G534A(Glu178/Glu) polymorphism in the HSD11B2 gene is associated with hypertension. Investigate the frequency of the G534A polymorphism and its correlation with the glucocorticoid profile in Chilean essential hypertensive and normotensive subjects. METHODS Essential hypertensive outpatients (n = 232) and normotensive subjects (n = 74) were recruited. A change in the AluI restriction enzyme digest pattern, caused by the presence of the G534A polymorphism, was utilized to screen DNA isolated from leukocytes within the cohort before confirmation by sequencing. Plasma renin activity (PRA), serum aldosterone, F, and E were measured by radioimmunoassay. Urinary tetrahydrocortisol (THF), 5α-tetrahydrocortisol (5α-THF), and tetrahydrocortisone (THE) were measured by gas chromatography-mass spectrometry. RESULTS G534A polymorphism frequency was similar between hypertensive patients (19 of 232; 8.2%) and normotensive subjects (7 of 74; 9.5%). When categorized by presence or absence of the G534A polymorphism, no significant differences in the serum F/E ratio or other measured biochemical variables were detected. Despite a previous report that the G534A polymorphism is associated with a neighboring C468A (Thr156/Thr) polymorphism, analysis within our cohort showed that only one patient in each group presented with this double polymorphism. CONCLUSIONS We report the frequency of the G534A polymorphism in the Spanish-Amerindian population. No correlation was detected between this polymorphism and the presence of hypertension and biochemical parameters in this Chilean cohort.

Urinary cortisol to cortisone metabolites ratio in prednisone-treated and spontaneously hypertensive patients

Objective and methods Prednisone and its active metabolite prednisolone, both substrates for 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), may represent a pharmacological challenge for the enzyme. The aim of the present work was to define the possible role of abnormal cortisol/cortisone handling, as revealed by an urinary tetrahydrocortisol + allotetrahydrocortisol (THFs)/tetrahydrocortisone (THE) ratio between 1.5 and 3.0, by measuring urinary cortisol and cortisone metabolites in: normotensive individuals (n = 100) who received 7–8 mg/day of oral prednisone and were then followed for development of hypertension; essential hypertensive (EH) participants from primary care (n = 103); and EH hypertensive patients referred to the Hypertension Unit (n = 141). Results About one-third (14 out of 47, 30%) of glucorticoid-treated patients who developed hypertension showed a THFs/THE ratio >1.5, which was seen in 3% (n = 3) and 14% (n = 19) of primary and tertiary care hypertensive patients, respectively. A THFs/THE ratio >1.5 was associated with a 3.8-fold incremental risk of hypertension after glucocorticoid therapy, regardless of duration and intensity of prednisone therapy. Conclusions A number of EH patients and glucocorticoid-treated participants shared a similar phenotype, characterized by both arterial hypertension and elevated urinary THFs/THE ratio. Such a phenotype is more common in severely, rather than in mildly, hypertensive patients.

Blood and Alveolar Toluene Concentrations in Workers during the Workshift and the Morning After

Abstract Occupational toluene exposures were studied in workers during the workshift and the morning after by testing toluene concentrations in environmental air, alveolar air and blood. During the workshift, the environmental toluene concentration was measured by means of continuous sampling over the 7-hour workshift and by instantaneous sampling at random times during and at the end of the workshift. Alveolar toluene concentration was measured by means of expired-air samples which were collected simultaneously with the instantaneous environmental air samples. Blood toluene concentration was measured in venous blood samples collected at the end of the workshift. The results showed that the blood toluene concentrations correlated better with the environmental toluene concentrations measured continuously during all the time of exposure than with the instantaneous environmental toluene concentrations measured at the end of the workshift. However, the aveolar toluene concentrations correlated better with the...

Inflammatory bowel disease and patterns of volatile organic compounds in the exhaled breath of children: A case-control study using Ion Molecule Reaction-Mass Spectrometry

Inflammatory bowel diseases (IBD) profoundly affect quality of life and have been gradually increasing in incidence, prevalence and severity in many areas of the world, and in children in particular. Patients with suspected IBD require careful history and clinical examination, while definitive diagnosis relies on endoscopic and histological findings. The aim of the present study was to investigate whether the alveolar air of pediatric patients with IBD presents a specific volatile organic compounds’ (VOCs) pattern when compared to controls. Patients 10–17 years of age, were divided into four groups: Crohn’s disease (CD), ulcerative colitis (UC), controls with gastrointestinal symptomatology, and surgical controls with no evidence of gastrointestinal problems. Alveolar breath was analyzed by ion molecule reaction mass spectrometry. Four models were built starting from 81 molecules plus the age of subjects as independent variables, adopting a penalizing LASSO logistic regression approach: 1) IBDs vs. controls, finally based on 18 VOCs plus age (sensitivity = 95%, specificity = 69%, AUC = 0.925); 2) CD vs. UC, finally based on 13 VOCs plus age (sensitivity = 94%, specificity = 76%, AUC = 0.934); 3) IBDs vs. gastroenterological controls, finally based on 15 VOCs plus age (sensitivity = 94%, specificity = 65%, AUC = 0.918); 4) IBDs vs. controls, built starting from the 21 directly or indirectly calibrated molecules only, and finally based on 12 VOCs plus age (sensitivity = 94%, specificity = 71%, AUC = 0.888). The molecules identified by the models were carefully studied in relation to the concerned outcomes. This study, with the creation of models based on VOCs profiles, precise instrumentation and advanced statistical methods, can contribute to the development of new non–invasive, fast and relatively inexpensive diagnostic tools, with high sensitivity and specificity. It also represents a crucial step towards gaining further insights on the etiology of IBD through the analysis of specific molecules which are the expression of the particular metabolism that characterizes these patients.