Exposure Assessment, Biological Monitoring, and Liver Function Tests of Operating Room Personnel Exposed to Halothane in Hamedan Hospitals, West of Iran.

BACKGROUND: Occupational exposure to halogenated hydrocarbons has been associated with halothane hepatitis, an increase of liver enzymes, and congenital malformations. The objectives of this study were to investigate whether bromide, a urinary metabolite of halothane, could be used as a biological marker of exposure to this anesthetic gas and assessment of associated exposure to halothane with any significant changes in conventional parameters of liver function (serum aminotransferase activities). STUDY DESIGN: A cross-sectional study. METHODS: Seventy-five anesthesiologists, anesthesia nurses, operating room nurses, and surgeons (exposed group) and 75 matched unexposed individuals (reference group) were selected randomly from two public hospitals in Hamadan City, western Iran.  Atmospheric concentrations of halothane in the breathing zone of the exposed subjects and urinary bromide levels were measured by headspace gas chromatography. Similarly, serum activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured by the enzymatic method using an automatic Prestige instrument. RESULTS: Mean atmospheric concentrations of halothane and urinary bromide levels for exposed subjects were 1.49 ±1.36 ppm and 0.83 ±0.29 mM, respectively. A relatively good correlation was found between exposure to halothane and urinary bromide levels (r=0.38). The chi-squared test results showed that the proportions of the subjects with abnormal ALT and AST among the women exposed were significantly higher than those of reference individuals (P<0.05). CONCLUSIONS: Urinary bromide can be used as a potential biomarker of exposure to halothane, although additional studies are necessary to further validate these initial findings.

[Determination of total Bromine in urine by inductively coupled plasma mass spectrometry (ICP-MS)].

OBJECTIVE: To establish a method to determine total bromine in urine. METHOD: Diluted urine samples were directly introduced into ICP-MS then quantized by standard curve. RESULT: Total bromine in urine was linear within 1.0~50 mg/L with r > 0.999, When spiked at a concentration of 0.020 mg/L, 0.050 mg/L, 0.150 mg/L, the recovery was 95%~98%, intra-assay precision was 1.4% 3.2%, inter-assay precision was 3.4% to 5.0%. Urine could store in -20 °C refrigerator 3 months without any bromine loss. CONCLUSION: Using ICP-MS to determine the urinary total bromine, the method is fast, accurate, wide linear range of features, could meet with the requirement of Part 5 of occupational health standards guide: Method determination of chemical substances in biological materials (GBZ/T 210.5-2008), a strong competitive advantage in a wide range of survey, suitable for promotion.

The metabolism of 4-bromoaniline in the bile-cannulated rat: application of ICPMS ((79/81)Br), HPLC-ICPMS & HPLC-oaTOFMS.

1. An excretion balance study was performed following i.p. administration of 4-bromoaniline (50 mg kg(-1)) to bile-cannulated rats, using bromine-detected ((79/81)Br) ICPMS for quantification. Approximately 90% of the dose was recovered in urine (68.9 ± 3.6%) and bile (21.4 ± 1.4%) by 48 h post-administration. 2. HPLC-ICPMS ((79/81)Br) was used to selectively detect and profile the major urinary and biliary-excreted metabolites and determined that the 0-12 h urine contained at least 21 brominated metabolites with 19 bromine-containing peaks observed in the 6-12 h bile samples. 3. The urinary and biliary metabolites were subsequently profiled using HPLC-oaTOFMS. By exploiting the distinctive bromine isotope pattern ca. 60 brominated metabolites were detected in the urine in negative electrospray ionisation (ESI) mode while bile contained ca. 21. 4. While a large number of bromine-containing metabolites were detected, the profiles were dominated by a few major components with the bulk of the 4-bromoaniline-related material in urine accounted for by 4-bromoanaline O-sulfate (∼75% of the total by ICPMS, 84% by TOFMS). In bile a hydroxylated N-acetyl compound was the major metabolite detected, forming some ∼65% of the 4-bromoaniline-related material by ICPMS (37% by TOFMS).

Analysis of exposure biomarker relationships with the Johnson SBB distribution.

Application of the Johnson bivariate S(B) distribution, or alternatively the S(BB) distribution, is presented here as a tool for the analysis of concentration data and in particular for characterizing the relationship between exposures and biomarkers. Methods for fitting the marginal S(B) distributions are enhanced by maximizing the Shapiro-Wilk W statistic. The subsequent goodness of fit for the S(BB) distribution is evaluated with a multivariate Z statistic. Median regression results are extended here with methods for calculating the mean and standard deviation of the conditional array distributions. Application of these methods to the evaluation of the relationship between exposure to airborne bromopropane and the biomarker of serum bromide concentration suggests that the S(BB) distribution may be useful in stratifying workers by exposure based on using a biomarker. A comparison with the usual two-parameter log-normal approach shows that in some cases the S(BB) distribution may offer advantages.

Re-evaluation of the "week-end effect" data: possible role of urinary copper and phosphorus in the pathogenesis of renal calculi.

Early morning urinary concentrations of 10 elements which had demonstrated a "week-end effect" in a previous study, were subjected to a normalization procedure thereby allowing a re-assessment of their potential role in urolithiasis. After transformation of each concentration to a weighted proportion of the total concentration on each day, only Cu and P values were significantly different for kidney stone formers and healthy controls on all three days indicating that these elements may play a role in the pathogenesis of renal calculi. The results obtained in this study demonstrate that a more meaningful picture of the possible differences in the urinary concentrations of stone formers and normal controls might emerge if "proportional" rather than "raw" concentrations are compared.

Determination of iodine and bromine in plasma and urine by inductively coupled plasma mass spectrometry.

The simultaneous determination of iodine and bromine in plasma and urine by inductively coupled plasma mass spectrometry, using a Nermag prototype instrument, is described. The sample preparation involves only a 10-fold dilution with a diluent containing europium as an internal standard followed by direct nebulisation in the plasma. The iodine, bromine and europium ions are measured at m/z = 127, 79, and 153, respectively. The sensitivity of the method, with detection limits of 1.6 and 52 micrograms l-1 for iodine and bromine, respectively, is satisfactory for clinical applications. The calibration graphs were linear over the ranges 0-400 micrograms l-1 and 0-40 mg l-1 for iodine and bromine, respectively, which are wide enough for most assays. The recoveries were close to 100% with coefficients of variation of less than 3%. The within-day and between-day reproducibility was about 5%. The concentrations of iodine and bromine in the plasma of 26 healthy individuals were 58 +/- 12 micrograms l-1 and 4.1 +/- 0.9 mg l-1, respectively. The amounts of iodine and bromine eliminated in urine were 94 +/- 97 micrograms per 24 h (range 27-403 micrograms per 24 h) and 3.6 +/- 1.7 mg per 24 h, respectively. These results are in agreement with reported values.

[Determination of bromide ions in total blood, plasma and urine by ion chromatography with amperometric detection].

A direct injection method is described for the determination of bromide ions in plasma and urine by ion chromatography. After being diluted 10-20 times with eluent, the sample was directly injected into an ion chromatograph equipped with amperometric detection. Calibration curves were obtained in the range of 0.05 to 5 micrograms/ml of bromide ions. The coefficient of variation was calculated to be in the range of 1.3-9.4% for 10 repeated measurements and recovery was over 93%. The correlation between analytical results by the proposed method (Y) and those by a spectrophotometric method (X) of 169 urine samples in fumigators was expressed by the equation Y = 0.952 + 1.012X (correlation coefficient (r): 0.952). On the other hand, the correlation between analytical results by the proposed method (Y) and those by neutron activation analysis (X) of 47 total-blood samples in fumigators was expressed by the equation Y = 1.070 + 0.841 X (correlation coefficient (r): 0.931). The correlation between analytical results by the proposed method (Y) and those by neutron activation analysis (X) of 40 plasma samples in healthy workers was expressed by the equation Y = 0.633 + 0.871 X (correlation coefficient (r): 0.955). The proposed method is much more practical than other methods such as the spectrophotometric method and neutron activation analysis in epidemiological studies, because the proposed method is highly accurate and reproducible over longer periods. The proposed method is useful in biological fluid monitoring of bromide ions.

Bromine levels in human serum, urine, hair. Short communication.

Much is known about the essentiality of the halogens fluorine (F), chlorine (Cl), and iodine (I), but very little has been discussed with respect to bromine (Br). As a member of the halogen family its chemical properties are comparable to those of other halogens, but its presence has been masked by the presence of I and Cl in chemical analyses. By virtue of new technology and a special computerized machine called the Kevex Model 0600 Energy Dispersive X-Ray Induced X-Ray Fluorescence Spectrometer (EDXRF), we can specifically identify bromine in different compartments and verify its concentration accurately. In order to establish standard values of Br concentrations and evaluate the nature of its presence in humans, samples of serum, urine, and hair were collected from ten healthy adult males and analyzed for bromine content. Our samples had normal distributions, with serum bromine levels ranging from 3.2 to 5.6 micrograms/mL, urine levels between 0.3 to 7.0 micrograms/mL, and hair levels determined from 1.1 to 49.0 micrograms/mL. These levels, especially those of serum bromine, have been encountered by other examiners whose samples also had normal distributions. These findings suggest to us that bromine may well be an essential trace element, as are its other halogen family members.

The rapid determination of total bromine and iodine in biological fluids by neutron activation.

Total bromine and iodine are instrumentally determined in 1 mL samples of body fluids by neutron activation under a boron shield at normal concentration levels. No sample treatment is necessary. Bromine is determined by its 80Br nuclide (617.0 keV; T1/2 = 18.0 min) and iodine by its 128I nuclide (442.7 keV;T1/2 = 25.0 min). The method is rapid; four bromine and two iodine determinations can be done in one hour. Bromine and iodine can be detected down to 14 micrograms/dL (1.75 mumol/L) and 2.9 micrograms/dL (0.23 mumol/L), respectively.

The fate of brominated soya oil in the animal body.

1. The bromine-containing material accumulated in tissues of rats dosed with brominated soya oil gradually decreased when the oil was no longer administered. 2. G.l.c. of the transesterified ether extracts of tissues from dosed animals showed 9,10-dibromostearic acid in extracts from fat, heart, kidney, liver and muscle with much smaller amounts of 9,10,12,13-tetrabromostearic acid in all extracts except that from liver. 3. An ether-soluble bromine-containing metabolite excreted by rats dosed with brominated soya oil was tentatively identified as 5,6-dibromosebacic acid. 4. The same metabolite was excreted by rabbits, rats and marmosets dosed with 9,10-dibromostearic acid.

[Structure of bromine containing metabolites of carbromal (author's transl)]. / Strukturnachweis von bromhaltigen Carbromalmetaboliten

Isolation of three bromine containing metabolites from human urine is described and their chemical structure is proved by comparison of their physical properties with those of synthetically prepared substances. 2-Bromo-2-ethyl-butyramide, a pharmacologically active product, is showed to be the most important bromine containing metabolite by volume. In 3-position hydroxylated metabolites of carbromal, 3-hydroxy-carbromal and 2-Bromo-2-ethyl-3-hydroxy-butyramide have same physical properties as the synthesized DL-threo--diastereomeres.

[Bromide vegetating skin diseases after treatment by a bromocalcic specialty]. / Bromides végétantes après traitement par une spécialité bromocalcique

The authors report on a case of vegetating bromoderma observed after therapy with bromocalcic speciality (Calcibronat). Repeated bromine determinations in body fluids enabled, while reconsidering the metabolism of this halogen, to monitor its elimination.