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1.
J Trace Elem Med Biol ; 49: 113-118, 2018 Sep.
Article in English | MEDLINE | ID: mdl-29895359

ABSTRACT

The nutritional availability of selenium (Se) is highly dependent on its chemical form because chemical form affects absorption, distribution, metabolism, and excretion. We evaluated the effects of administration route and dose on the bioavailability of nine Se compounds found in biota, the so-called bioselenocompounds, such as selenite, selenate, selenocyanate (SeCN), Se-methylselenocysteine (MeSeCys), selenomethionine (SeMet), selenohomolanthionine (SeHLan), selenocystine (SeCys2), 1ß-methylseleno-N-acetyl-d-galactosamine (SeSug1), and trimethylselenonium ion (TMSe). We determined the bioavailability of bioselenocompounds recovered as urinary selenometabolites and serum selenoproteins from urine and serum of Se-deficient rats after the administration of bioselenocompounds by speciation analysis. Urinary Se was more easily recovered than serum selenoproteins, suggesting that the speciation of urinary Se is a better tool to indicate Se status in the body. The intravenous administration of bioselenocompounds showed different Se bioavailability from the oral administration. Intestinal microflora might be involved in the bioavailability of some bioselenocompounds, such as SeCN, MeSeCys, and SeSug1.


Subject(s)
Selenium Compounds/urine , Administration, Oral , Animals , Chromatography, Liquid , Cyanates/urine , Cystine/analogs & derivatives , Gastrointestinal Microbiome/physiology , Glutathione Peroxidase/metabolism , Male , Mass Spectrometry , Organoselenium Compounds/urine , Rats , Rats, Wistar , Selenocysteine/analogs & derivatives , Selenocysteine/urine , Selenomethionine/urine , Selenoproteins/urine
2.
Ann Occup Hyg ; 54(6): 678-91, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20530123

ABSTRACT

Urinary 1,6-hexamethylene diamine (HDA) may serve as a biomarker for systemic exposure to 1,6-hexamethylene diisocyanate (HDI) in occupationally exposed populations. However, the quantitative relationships between dermal and inhalation exposure to HDI and urine HDA levels have not been established. We measured acid-hydrolyzed urine HDA levels along with dermal and breathing-zone levels of HDI in 48 automotive spray painters. These measurements were conducted over the course of an entire workday for up to three separate workdays that were spaced approximately 1 month apart. One urine sample was collected before the start of work with HDI-containing paints and subsequent samples were collected during the workday. HDA levels varied throughout the day and ranged from nondetectable to 65.9 microg l(-1) with a geometric mean and geometric standard deviation of 0.10 microg l(-1) +/- 6.68. Dermal exposure and inhalation exposure levels, adjusted for the type of respirator worn, were both significant predictors of urine HDA levels in the linear mixed models. Creatinine was a significant covariate when used as an independent variable along with dermal and respirator-adjusted inhalation exposure. Consequently, exposure assessment models must account for the water content of a urine sample. These findings indicate that HDA exhibits a biphasic elimination pattern, with a half-life of 2.9 h for the fast elimination phase. Our results also indicate that urine HDA level is significantly associated with systemic HDI exposure through both the skin and the lungs. We conclude that urinary HDA may be used as a biomarker of exposure to HDI, but biological monitoring should be tailored to reliably capture the intermittent exposure pattern typical in this industry.


Subject(s)
Air Pollutants, Occupational/urine , Cyanates/urine , Diamines/urine , Occupational Exposure/statistics & numerical data , Adult , Air Pollutants, Occupational/analysis , Air Pollution, Indoor/analysis , Air Pollution, Indoor/statistics & numerical data , Automobiles , Biomarkers/urine , Creatinine/blood , Creatinine/urine , Cyanates/analysis , Diamines/analysis , Dose-Response Relationship, Drug , Environmental Monitoring , Half-Life , Humans , Hydrolysis , Inhalation Exposure/analysis , Inhalation Exposure/statistics & numerical data , Isocyanates , Linear Models , Male , Middle Aged , Occupational Exposure/analysis , Paint , Protective Clothing/statistics & numerical data , Respiratory Protective Devices , Skin Absorption , Workplace , Young Adult
3.
J Environ Monit ; 12(3): 591-9, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20445846

ABSTRACT

Urine amine levels used as biomarkers of diisocyanate exposure have usually been normalized with creatinine concentration. The suitability of using creatinine concentration or specific gravity for these biomarkers in exposure assessment has not been established. We investigated the effect of creatinine concentration and specific gravity on urine 1,6-hexamethylene diamine (HDA) levels in multiple mixed linear regression models using quantitative dermal and inhalation exposure data derived from a survey of automotive spray painters occupationally exposed to 1,6-hexamethylene diisocyanate (HDI). Painters' dermal and breathing-zone HDI exposure were monitored for an entire workday for up to three workdays spaced approximately one month apart. One urine sample was collected before the start of work with HDI-containing paints, and multiple samples were collected throughout the workday. Both creatinine concentration and specific gravity were highly significant predictors (p < 0.0001) of urine HDA levels. When these two were used together in the same model, creatinine remained highly significant (p < 0.0001), but specific gravity decreased in significance (p-values 0.10-0.17). We used different individual factors to determine which affected creatinine and specific gravity. Urine collection time was a highly significant predictor of specific gravity (p = 0.003) and creatinine concentration (p = 0.001). Smoker status was significant (p = 0.026) in the creatinine model. The findings indicate that creatinine concentration is more appropriate to account for urine water content than specific gravity and that creatinine is best used as an independent variable in HDI exposure assessment models instead of traditional urine normalization with creatinine concentration.


Subject(s)
Creatinine/urine , Diamines/urine , Occupational Exposure/analysis , Urine/chemistry , Adult , Cyanates/metabolism , Cyanates/urine , Humans , Isocyanates , Linear Models , Male , Middle Aged , Models, Biological , Specific Gravity , Young Adult
4.
Occup Environ Med ; 63(9): 624-31, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16728504

ABSTRACT

OBJECTIVES: To study inhalation and dermal exposure to hexamethylene diisocyanate (HDI) and its oligomers as well as personal protection equipment (PPE) use during task performance in conjunction with urinary hexamethylene diamine (HDA) in car body repair shop workers and industrial spray painters. METHODS: Personal task based inhalation samples (n = 95) were collected from six car body repair shops and five industrial painting companies using impingers with di-n-butylamine (DBA) in toluene. In parallel, dermal exposure was assessed using nitril rubber gloves. Gloves were submerged into DBA in toluene after sampling. Analysis for HDI and its oligomers was performed by LC-MS/MS. Urine samples were collected from 55 workers (n = 291) and analysed for HDA by GC-MS. RESULTS: Inhalation exposure was strongly associated with tasks during which aerosolisation occurs. Dermal exposure occurred during tasks that involve direct handling of paint. In car body repair shops associations were found between detectable dermal exposure and glove use (odds ratio (OR) 0.22, 95% confidence interval (CI) 0.09 to 0.57) and inhalation exposure level (OR 1.34, 95% CI 0.97 to 1.84 for a 10-fold increase). HDA in urine could be demonstrated in 36% and 10% of car body repair shop workers and industrial painting company workers respectively. In car body repair shops, the frequency of detectable HDA was significantly elevated at the end of the working day (OR 2.13, 95% CI 1.07 to 4.22 for 3-6 pm v 0-8 am). In both branches HDA was detected in urine of approximately 25% of the spray painters. In addition HDA was detected in urine of a large proportion of non-spray painters in car body repair shops. CONCLUSION: Although (spray) painting with lacquers containing isocyanate hardeners results in the highest external exposures to HDI and oligomers, workers that do not perform paint related tasks may also receive a considerable internal dose.


Subject(s)
Air Pollutants, Occupational/toxicity , Cyanates/toxicity , Occupational Exposure/adverse effects , Paint/toxicity , Air Pollutants, Occupational/urine , Automobiles , Cyanates/urine , Environmental Monitoring/methods , Humans , Industry , Inhalation Exposure/adverse effects , Isocyanates , Occupational Exposure/analysis
5.
Proc Biol Sci ; 269(1493): 853-60, 2002 Apr 22.
Article in English | MEDLINE | ID: mdl-11958718

ABSTRACT

Elephants have extraordinary olfactory receptive equipment, yet this sensory system has been only minimally investigated in wild elephants. We present an in-depth study of urinary chemical signals emitted by individual, behaviourally characterized, wild male African elephants, investigating whether these compounds were the same, accentuated, or diminished in comparison with captive individuals. Remarkably, most emitted chemicals were similar in captive and wild elephants with an exception traced to drought-induced dietary cyanates among wild males. We observed developmental changes predominated by the transition from acids and esters emitted by young males to alcohols and ketones released by older males. We determined that the ketones (2-butanone, acetone and 2-pentanone, and 2-nonanone) were considerably elevated during early musth, musth and late musth, respectively, suggesting that males communicate their condition via these compounds. The similarity to compounds released during musth by Asian male elephants that evoke conspecific bioresponses suggests the existence of species-free 'musth' signals. Our innovative techniques, which allow the recognition of precise sexual and musth states of individual elephants, can be helpful to managers of both wild and captive elephants. Such sampling may allow the more accurate categorization of the social and reproductive status of individual male elephants.


Subject(s)
Elephants/physiology , Smell/physiology , Alcohols/urine , Animal Communication , Animals , Animals, Wild/physiology , Animals, Wild/urine , Animals, Zoo/physiology , Animals, Zoo/urine , Cyanates/urine , Elephants/urine , Isocyanates/urine , Ketones/urine , Male , Odorants , Reproduction/physiology , Urine/chemistry
6.
J Chromatogr B Biomed Sci Appl ; 709(1): 150-6, 1998 May 08.
Article in English | MEDLINE | ID: mdl-9653937

ABSTRACT

We established a high-performance liquid chromatographic method for separating and quantifying carbamylated dehydroascorbate derivative (CDA), a reaction product of cyanate with dehydroascorbate. The separation of CDA from interfering substances was achieved by anion-exchange HPLC using a TSK gel SAX (250x4.6 mm I.D.) column and 0.12 M NaCl eluent. The detection of CDA was achieved through two steps: (1) degradation of CDA to cyanate and amino compounds in alkaline solution, and (2) detection of these products by an indophenol reaction. For the processing of plasma and urine samples, anion-exchange solid-phase extraction was used. The detection limit for quantitative determination was 0.1 microM CDA (S/N=3). The linear range found applying the optimized conditions was 0.2 to 200 microM. The intra- and inter-day assay precision (R.S.D.) of CDA (10 microM) were 4.8 and 7.2% for rat plasma, and 4.0 and 4.9% for rat urine, respectively. The usefulness of the present method was proved by the application to plasma and urine samples. The study of the biokinetics of CDA in rats revealed that the elimination of CDA is due to urinary excretion.


Subject(s)
Chromatography, High Pressure Liquid/methods , Cyanates/chemistry , Dehydroascorbic Acid/chemistry , Animals , Cyanates/blood , Cyanates/urine , Dehydroascorbic Acid/blood , Dehydroascorbic Acid/urine , Male , Rats , Rats, Wistar
7.
Chem Res Toxicol ; 8(6): 891-9, 1995 Sep.
Article in English | MEDLINE | ID: mdl-7492739

ABSTRACT

Bioactivation of the formamide N-formylamphetamine (NFA) to 1-methyl-2-phenylethyl isocyanate (MPIC) was investigated in rats by screening bile and urine for conjugates subsequent to the phase I event. NFA was administered to rats as a mixture of protio- and pentadeuteriophenyl analogues to gain insight into the carbamoylating activity of MPIC when traced by electrospray liquid chromatography/mass spectrometry (LC/MS). An LC/MS contour generated by recording the summed mass spectrum as a function of chromatographic retention time allowed four biliary metabolites to be identified from four sets of doublets, with the peak of each doublet offset by 5 amu and ca. 0.07 min. Tandem mass spectrometry experiments allowed these metabolites to be attributed structurally to the glutathione, cysteinylglycine, cysteine, and N-acetylcysteine conjugates of the isocyanate MPIC. These assignments were subsequently validated by comparison of the LC/MS properties of the metabolites to synthetic reference compounds. Only the carbamoylated N-acetylcysteine conjugate was detected in urine. The observed excretion in bile of all metabolites of the mercapturate pathway is novel for formamide metabolism. NFA can thus be added to the short list of compounds that are eliminated in this fashion. Factors envisioned as contributory to this metabolic profile in bile include hepatorenal, enterohepatic, and biliary-hepatic cycling, in addition to possible equilibrium exchange of the isocyanate from thiocarbamate conjugates to endogenous free thiols during the course of biliary transit.


Subject(s)
Amphetamines/metabolism , Cyanates/metabolism , Isocyanates/metabolism , Mass Spectrometry/methods , Animals , Bile/chemistry , Biotransformation , Cyanates/urine , Gas Chromatography-Mass Spectrometry , Isocyanates/urine , Isotopes , Male , Rats , Rats, Sprague-Dawley
8.
J Egypt Public Health Assoc ; 70(1-2): 1-14, 1995.
Article in English | MEDLINE | ID: mdl-17214197

ABSTRACT

Mercury vapor exposed workers may show ocular changes, as well as other systems affection. A sample of 84 workers in preparing mercury fulminate were examined for conjunctival corneal and lenticular manifestation of long duration exposure, together with mercury urinary output. Lens changes were found in 50% of the involved workers while keratopathy as recorded in 34.5% of them. No statistically significant association was found between the occurrence of eye lesions and levels of urinary elimination of mercury. These results suggest local absorption of this element is most probably the underlying cause of ocular affection.


Subject(s)
Cyanates/adverse effects , Eye Diseases/chemically induced , Mercury/adverse effects , Occupational Exposure/adverse effects , Adult , Cyanates/urine , Eye Diseases/diagnosis , Eye Diseases/physiopathology , Humans , Male , Mercury/urine , Middle Aged
9.
Analyst ; 119(9): 2051-5, 1994 Sep.
Article in English | MEDLINE | ID: mdl-7978332

ABSTRACT

Hexamethylene-1,6-diamine (HDA) and isophoronediamine (IPDA) in hydrolysed human urine were studied as their perfluorofatty anhydride derivatives. Liquid chromatography and mass spectrometry with thermospray ionization were used. For quantitative analysis, the negative ions monitored were the m/z = 407 and 461, corresponding to the (M-1)- ions of the HDA-pentafluoropropionic anhydride (HDA-PFPA) and the IPDA-PFPA derivatives, respectively, and the m/z = 411 ions of the tetradeuterium-labelled HDA-PFPA (internal standard). Human urine was spiked with HDA and IPDA to six different concentrations in the range 2.5-20 micrograms l-1. Tetradeuterated HDA was used as the internal standard for the determination of both HDA and IPDA. The linear calibration curves obtained passed virtually through the origin, and the correlation coefficients were 0.998 for HDA and 0.973 for IPDA. The over-all precision for human urine spiked to a concentration of 5 micrograms l-1 of HDA and 25 micrograms l-1 of IPDA was found to be 5 and 14% (n = 5), respectively. The m/z = (M-1)- fragments, defined as twice the signal-to-noise ratio, were at the 0.5-1 pg level for the HDA and IPDA derivatives. The method presented made it possible to perform about 400 chromatographic runs during 24 h.


Subject(s)
Cyanates/urine , Cyclohexylamines/urine , Diamines/urine , Environmental Monitoring/methods , Isocyanates/urine , Chromatography, Liquid , Humans , Hydrolysis , Male , Mass Spectrometry , Monitoring, Physiologic
10.
J Chromatogr B Biomed Appl ; 656(2): 319-28, 1994 Jun 17.
Article in English | MEDLINE | ID: mdl-7987483

ABSTRACT

A GC method using a novel derivatization reagent, 2',2',2-trifluoroethyl chloroformate (TFECF), for the derivatization of primary and secondary aliphatic amines with the formation of carbamate esters is presented. The method is based on a derivatization procedure in a two-phase system, where the carbamate ester is formed. The method is applied to the determination of 1,6-hexamethylene diamine (HDA) in aqueous solutions and human urine, using capillary GC. Detection was performed using thermionic specific detection (TSD) and mass spectrometry (MS)-selective-ion monitoring (SIM) using electron-impact (EI) and chemical ionization (CI) with ammonia monitoring both positive (CI)+ and negative ions (CI)-. Quantitative measurements were made in the chemical ionization mode monitoring both positive and negative ions. Tetra-deuterium-labelled HDA (TDHDA; H2NC2H2(CH2)4C2H2NH2) was used as the internal standard for the GC-MS analysis. In CI+ the m/z 386 and the m/z 390 ions corresponding to the [M + 18]+ ions (M = molecular ion) of HDA-TFECF and TDHDA-TFECF were measured; in CI- the m/z 267 and the m/z 271 ions corresponding to the [M - 101]- ions. The overall recovery was found to be 97 +/- 5% for a HDA concentration of 1000 micrograms/l in urine. The minimal detectable concentration in urine was found to be less than 20 micrograms/l using GC-TSD and 0.5 micrograms/l using GC-SIM. The overall precision for the work-up procedure and GC analysis was ca. 3% (n = 5) for 1000 micrograms/l HDA-spiked urine, and ca. 4% (n = 5) for 100 micrograms/l. The precision using GC-SIM for urine samples spiked to a concentration of 5 micrograms/l was found to be 6.3% (n = 10).


Subject(s)
Cyanates/analysis , Diamines/analysis , Environmental Monitoring , Chromatography, Gas , Cyanates/urine , Diamines/urine , Humans , Hydrolysis , Indicators and Reagents , Isocyanates , Male , Mass Spectrometry
11.
Chem Res Toxicol ; 6(3): 335-40, 1993.
Article in English | MEDLINE | ID: mdl-8318655

ABSTRACT

Following administration to rats of a single ip dose (6.6 mg kg-1) of the investigational antitumor agent caracemide (N-acetyl-N,O-bis[methylcarbamoyl]hydroxylamine), the mercapturic acid derivative N-acetyl-S-(N-methylcarbamoyl)cysteine (AMCC) was identified in urine by thermospray LC-MS. Quantification of this conjugate was carried out by stable isotope dilution thermospray LC-MS, which indicated that the fraction of the caracemide dose recovered as AMCC in 24-h urine collections was 54.0 +/- 5.5% (n = 4). Since AMCC is known to represent a major urinary metabolite of methyl isocyanate (MIC) in the rat, the results of this study support the contention that caracemide yields MIC as a toxic intermediate in vivo. Furthermore, with the aid of a specifically deuterium-labeled analog of caracemide ([carbamoyloxy-C2H3]caracemide), it was shown that the methylcarbamoyl group of AMCC derived from both the O-methylcarbamoyl (72%) and N-methylcarbamoyl (28%) side chains of the drug. In view of these findings, it is concluded that caracemide acts as a latent form of MIC in vivo and that this reactive isocyanate (or labile S-linked conjugates thereof) may contribute to the antitumor properties and/or adverse side-effects of caracemide.


Subject(s)
Antineoplastic Agents/pharmacokinetics , Cyanates/pharmacokinetics , Hydroxyurea/analogs & derivatives , Isocyanates , Acetylcysteine/analogs & derivatives , Acetylcysteine/pharmacokinetics , Acetylcysteine/urine , Animals , Antineoplastic Agents/urine , Cyanates/toxicity , Cyanates/urine , Hydroxyurea/pharmacokinetics , Hydroxyurea/urine , Male , Rats , Rats, Sprague-Dawley
12.
J Rheumatol ; 20(2): 268-72, 1993 Feb.
Article in English | MEDLINE | ID: mdl-8474063

ABSTRACT

Gold based drugs and their metabolites have been characterized using reversed phase, ion pairing chromatography with an inductively coupled plasma mass spectrometer as an element specific detector. For a patient receiving gold sodium thiomalate the principal gold species in the urine is [Au(CN)2]-, which is also seen in a low molecular weight infiltrate of the blood. The same compound is also identified in the urine and blood of a patient taking auranofin and in patients taking solganol. This represents the first identification of a specific gold metabolite in biological fluids taken from patients undergoing gold therapy and the first evidence that different gold drugs have common metabolites.


Subject(s)
Arthritis, Rheumatoid/drug therapy , Cyanates/pharmacokinetics , Gold/pharmacokinetics , Anions , Arthritis, Rheumatoid/blood , Arthritis, Rheumatoid/urine , Auranofin/blood , Auranofin/urine , Aurothioglucose/blood , Aurothioglucose/urine , Cyanates/blood , Cyanates/urine , Gold/blood , Gold/urine , Gold Sodium Thiomalate/blood , Gold Sodium Thiomalate/urine , Humans
13.
Drug Metab Dispos ; 21(1): 93-9, 1993.
Article in English | MEDLINE | ID: mdl-8095233

ABSTRACT

Urine is the major route of excretion of N'-(2-chloroethyl)-N-[2-(methylsulfinyl)ethyl]-N'-nitrosourea (CMSOEN2), N'-(2-chloroethyl)-N-[2-(methylsulfonyl)ethyl]-N'-nitrosourea (CMSO2EN2), and their metabolites in the rat. Labeling the two compounds with 14C in three different positions facilitated their metabolic study in animals. The 14C-ethyl species were chosen in order to investigate the presence of unchanged compounds and that of the denitrosated forms. With the same 14C label position, we showed that isolated metabolites derived from this part of the molecule were degradation products of alkylated glutathione and/or cysteine. They are common to both CMSOEN2 and CMSO2EN2, namely thiodiacetic acid and its sulfoxide, the sum of which represents about half of urinary radioactivity. N-acetyl carboxymethylcysteine and N-acetyl hydroxyethylcysteine, accounting for approximately 6% to 7% of the eliminated 14C radioactivity, were also characterized. However, four minor metabolites corresponding to less than 10% of the excreted radioactivity remained unidentified. With the [14C]cysteamine and [14C]carbonyl labels related to the isocyanate moiety behavior, we indirectly showed that more than 60% to 70% of the excreted metabolites were carbamoylation products of endogenous substrates. A small amount of free amines, 2-methylsulfinylethylamine and/or 2-methylsulfonylethylamine, representing 15%-16% of the eliminated radioactivity, was also detected. The total data confirm the predominant function of glutathione and/or cysteine in the detoxifying system of the chloroethyl moieties and reveal the unexpected but important role played by carbamoylation reactions in the metabolic fate of the drug isocyanate moieties.


Subject(s)
Antineoplastic Agents/urine , Cysteamine/analogs & derivatives , Cysteamine/urine , Nitrosourea Compounds/urine , Animals , Carbon Radioisotopes , Cyanates/urine , Rats , Rats, Wistar
14.
Chem Res Toxicol ; 4(5): 560-5, 1991.
Article in English | MEDLINE | ID: mdl-1793806

ABSTRACT

Benzyl selenocyanate (BSC), a synthetic organoselenium compound, has been shown to inhibit chemically induced tumors in several animal model systems. However, it is not known whether BSC or one of its metabolites is responsible for the chemopreventive effect. An initial approach to this question requires the structural elucidation of BSC metabolites in vitro and in vivo. To determine the structures of BSC metabolites in vitro, we studied the metabolism of [14C]BSC using Aroclor-induced rat liver 9000g supernatant. Under these conditions, BSC was partially converted to dibenzyl diselenide (DDS) and phenylmethaneseleninic acid. The metabolism of [14C]BSC (12.5 mg/kg body weight, 8 mCi/mmol, oral administration) in male F344 rats was also studied. Excretion was monitored by measurement of radioactivity as well as by selenium content using atomic absorption spectrophotometry (AAS). The results indicate that urine was the major route of excretion. Approximately 22% of the dose was excreted in the urine over the course of 35 days; however, a large portion (approximately 70%) of the dose remained in the body. Benzoic acid, hippuric acid, and their sulfate and glucuronide conjugates, accounting for 16% of the dose, were identified in the urine. The formation of these metabolites indicates that BSC is metabolized in part via bond cleavage between the benzyl moiety and the selenocyanate function. Additional support for this cleavage was obtained from fecal analysis; over the course of 23 days 9% of the selenium (AAS) but only less than 1% of the radioactivity was recovered in feces. No radioactivity was detected in the exhaled air. We also studied the metabolism of [14C]DDS (17.3 mg/kg body weight, 2.5 mCi/mmol) in male F344 rats.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Cyanates/metabolism , Organoselenium Compounds/metabolism , Amino Acids/chemistry , Animals , Benzyl Compounds/metabolism , Chromatography, High Pressure Liquid , Cyanates/chemistry , Cyanates/urine , Deoxyribonuclease I/chemistry , Endopeptidases/chemistry , Feces/chemistry , Glutathione Peroxidase/chemistry , Hemoglobins/chemistry , In Vitro Techniques , Liver/metabolism , Male , Mass Spectrometry , Organoselenium Compounds/chemistry , Organoselenium Compounds/urine , Rats , Rats, Inbred F344 , Ribonucleases/chemistry , Spectrophotometry, Atomic , Spectrophotometry, Ultraviolet
15.
Mutagenesis ; 6(3): 189-92, 1991 May.
Article in English | MEDLINE | ID: mdl-1881349

ABSTRACT

This study was conducted to evaluate the cytogenetic effects in male workers exposed to mercury fulminate. A total of 29 male workers and 29 age- and sex-matched controls were examined. The mean mercury level in urine from the exposed workers was 123.2 +/- 54.1 micrograms/l compared with 39.2 +/- 11.1 micrograms/l in the control group. The difference was statistically significant (P less than 0.001). Metaphase chromosomes were studied. Micronucleated peripheral blood lymphocytes were also analyzed in cytochalasin B blocked binucleated lymphocytes. The percentage of metaphases with chromosomal aberrations was significantly higher (P less than 0.001) in the exposed group (6.1 +/- 2.3) compared to the control group (2.8 +/- 0.7). The chromosomal aberrations detected were in the form of gaps, breaks and fragments. A significant increase in the incidence of micronucleated lymphocytes was found among the exposed group (7.1 +/- 4.2) compared to the control group (5.4 +/- 2.2) (P less than 0.01). The detected chromosomal damage correlated neither with the duration of exposure nor with the urinary mercury level.


Subject(s)
Air Pollutants, Occupational/adverse effects , Chemical Industry , Chromosome Aberrations , Cyanates/adverse effects , Mercury/adverse effects , Spindle Apparatus/drug effects , Adult , Cells, Cultured , Cohort Studies , Cyanates/urine , Humans , Lymphocytes/drug effects , Lymphocytes/ultrastructure , Male , Mercury/urine , Micronucleus Tests , Middle Aged , Mutagenicity Tests , Occupational Exposure , Spindle Apparatus/ultrastructure , Time Factors
16.
Chem Res Toxicol ; 4(2): 157-61, 1991.
Article in English | MEDLINE | ID: mdl-1782345

ABSTRACT

S-(N-Methylcarbamoyl)-N-acetylcysteine (AMCC), a chemically labile mercapturic acid conjugate, was identified by liquid chromatography-mass spectrometry (LC-MS) in the urine of rats dosed intraperitoneally with methyl isocyanate (MIC; 45.2 mumol). The corresponding cysteine conjugate, however, was not detected in urine. Following methylation, urine extracts were analyzed by thermospray LC-MS and the AMCC methyl ester was quantified by means of a stable isotope dilution assay procedure which utilized S-(N-methylcarbamoyl)-N-[2H3]-acetylcysteine [( 2H3]AMCC) as internal standard. The results showed that the fraction of the injected dose of MIC which appeared in 24-h urine collections as AMCC was 24.8 +/- 1.9% (mean +/- SD, N = 4). Thus, conjugation of MIC with glutathione (GSH), followed by metabolism of the resulting adduct to AMCC, appears to represent a quantitatively important pathway of biotransformation of MIC in the rat. However, in view of the known carbamoylating properties and in vitro cytotoxicity of S-linked conjugates of MIC, it seems unlikely that the GSH pathway of metabolism fulfills a conventional detoxification role in the case of MIC. In contrast, it is proposed that carbamate thioester conjugates of MIC, which can revert spontaneously to free MIC under physiological conditions, may actually contribute to the multisystem adverse effects of this highly toxic isocyanate in vivo.


Subject(s)
Cyanates/pharmacokinetics , Glutathione/metabolism , Isocyanates , Acetylcysteine/analogs & derivatives , Acetylcysteine/urine , Animals , Biotransformation , Chromatography, Liquid , Cyanates/metabolism , Cyanates/urine , Cysteine/analogs & derivatives , Cysteine/urine , Male , Mass Spectrometry , Rats , Rats, Inbred Strains
17.
J Chromatogr ; 516(2): 405-13, 1990 Sep 21.
Article in English | MEDLINE | ID: mdl-2079495

ABSTRACT

A capillary gas chromatographic (GC) method was developed for the determination of 1,6-hexamethylenediamine (HDA) in hydrolysed human urine. The method was based on a derivatization procedure with heptafluorobutyric anhydride. The amides formed were determined using capillary GC with selected ion monitoring in the chemical ionization mode with ammonia as reagent gas. The overall recovery was 34% for a concentration of 100 micrograms/l of HDA in urine. The minimum detectable concentration in urine was below 0.5 microgram/l. The precision of the method was 5% (n = 9). Deuterium-labelled HDA [H2NC2H2(CH2)4C2H2NH2] was used as the internal standard. A male subject was exposed to hexamethylene diisocyanate (HDI) for 7.5 h in a test chamber. The average air concentration of HDI was ca. 30 micrograms/m3, which corresponds to ca. 85% of the threshold limit value in Sweden (35 micrograms/m3). The half time of urinary levels of HDA was ca. 1.4 h and more than 90% of the urinary elimination was completed within 4 h after the exposure. The amount of HDA excreted in urine was ca. 10 micrograms, corresponding to ca. 10% of the estimated inhaled dose of HDI.


Subject(s)
Amines/urine , Chromatography, Gas/methods , Cyanates/urine , Cyanates/pharmacology , Diamines/urine , Humans , Isocyanates , Male , Mass Spectrometry , Reference Standards
18.
J Pharmacobiodyn ; 11(11): 730-5, 1988 Nov.
Article in English | MEDLINE | ID: mdl-3236205

ABSTRACT

Metabolic pathways of cyanate in rats were studied by means of measurements of cyanate, carbamyl phosphate and S-carbamyl group. Approximately 30-50% of cyanate administered to rats (0.5 mmol/kg body weight) was found in buffered gastric contents, and was also detected as ammonia liberated by acid hydrolysis. However, the gastric excretion of cyanate was a temporary phenomenon just after cyanate administration. Biliary and urinary excretion of cyanate and acid-soluble S-carbamyl group are minor metabolic pathways.


Subject(s)
Cyanates/pharmacokinetics , Animals , Bile/analysis , Carbamyl Phosphate/pharmacokinetics , Carbamyl Phosphate/urine , Cyanates/urine , Gastric Mucosa/metabolism , Hydrolysis , Liver/metabolism , Rats
19.
J Chromatogr ; 367(2): 385-92, 1986 Oct 03.
Article in English | MEDLINE | ID: mdl-3023414

ABSTRACT

Exposure of workers to toluene diisocyanate monomer in a factory producing flexible polyurethane was measured using impinger and reagent-impregnated filter sampling. These techniques yielded highly concordant results so that the facile filter techniques can be recommended. The personal exposures were compared with the individual excretion of amine metabolites from the parent toluene diisocyanates. The excretion was linearly related to the product of sampling time and concentration. The biological half-lives of the amines proved to be short so that urine should be sampled 2 h after the exposure. The percutaneous absorption of the monomers could also be controlled.


Subject(s)
Cyanates/urine , Occupational Diseases/chemically induced , Toluene 2,4-Diisocyanate/urine , Amines/urine , Gas Chromatography-Mass Spectrometry , Indicators and Reagents , Monitoring, Physiologic , Phenylenediamines/urine , Toluene 2,4-Diisocyanate/adverse effects
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