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1.
Environ Res ; 259: 119586, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39002635

RESUMO

Exposure to 1-bromopropane (1-BP) is an emerging environmental and health concern due to its increasing environmental prevalence. Although the health effects of 1-BP exposure have been under-recognized, current evidence suggests the possibility of adverse pulmonary health effects due to 1-BP exposure. However, the association between 1-BP exposure and asthma prevalence remains unclear. Thus, we aimed to examine the association between 1-BP exposure and asthma prevalence in the general population. Using nationally representative data, we explored the potential impacts of indoor air quality (IAQ)-related behavioral factors on the level of 1-BP exposure. This study included 1506 adults from the 2020-2021 Korea National Health and Nutrition Examination Survey. The prevalence of asthma was based on self-reported physician-diagnosed asthma. Urinary N-acetyl-S-(n-propyl)-L-cysteine (BPMA) levels were measured as a biomarker of 1-BP exposure, using high-performance liquid chromatography-mass spectrometry. Multiple logistic regression models were performed to investigate the associations between urinary BPMA metabolite and asthma prevalence after adjusting for potential confounders. Log-linear multiple regression models were used to examine the association between IAQ-related behavior and urinary BPMA concentration. Forty-seven individuals with asthma and 1459 without asthma were included. Individuals in the highest quartile of urinary BPMA concentration had a 2.9 times higher risk of asthma than those in the lowest quartile (odds ratio [OR]: 2.85, 95% confidence interval [CI]: 1.02-7.98). The combination of natural and mechanical ventilation was associated with a reduced urinary BPMA concentration. Our findings suggest that 1-BP exposure is associated with the prevalence of asthma in adults and revealed higher urinary levels of BPMA in our study population compared to those in other countries. Given the emerging importance of IAQ, actively managing and modifying behavioral patterns to reduce 1-BP exposure in indoor environments could substantially attenuate the risk of asthma-related to 1-BP exposure.


Assuntos
Asma , Hidrocarbonetos Bromados , Inquéritos Nutricionais , Humanos , Asma/epidemiologia , Asma/urina , Asma/induzido quimicamente , República da Coreia/epidemiologia , Feminino , Masculino , Adulto , Prevalência , Pessoa de Meia-Idade , Hidrocarbonetos Bromados/urina , Poluição do Ar em Ambientes Fechados/efeitos adversos , Exposição Ambiental/efeitos adversos , Adulto Jovem , Poluentes Atmosféricos/urina , Poluentes Atmosféricos/análise , Idoso
2.
Anal Bioanal Chem ; 409(5): 1323-1332, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27838756

RESUMO

Polybrominated diphenyl ethers (PBDEs), produced as flame retardants worldwide, have been phased-out in many countries, and chlorinated and non-chlorinated organophosphates and non-PBDE brominated formulations (e.g., Firemaster 550 (FM550)) have entered the consumers' market. Recent studies show that components of organophosphate esters and FM550 are frequently detected in many products common to human environments. Therefore, urinary metabolites of these compounds can be used as human exposure biomarkers. We developed a method to quantify nine compounds in 0.4 mL urine: diphenyl phosphate (DPhP), bis(1,3-dichloro-2-propyl) phosphate (BDCPP), bis-(1-chloro-2-propyl) phosphate, bis-2-chloroethyl phosphate, di-p-cresylphosphate, di-o-cresylphosphate (DoCP), di-n-butyl phosphate, dibenzyl phosphate (DBzP), and 2,3,4,5-tetrabromobenzoic acid. The method relies on an enzymatic hydrolysis of urinary conjugates of the target analytes, automated off-line solid phase extraction, reversed phase high performance liquid chromatography separation, and isotope dilution-electrospray ionization tandem mass spectrometry detection. The method is high-throughput (96 samples/day) with detection limits ranging from 0.05 to 0.16 ng mL-1. Spiked recoveries were 90-113 %, and interday imprecision was 2-8 %. We assessed the suitability of the method by analyzing urine samples collected from a convenience sample of adults (n = 76) and from a group of firefighters (n = 146). DPhP (median, 0.89; range, 0.26-5.6 ng mL-1) and BDCPP (median, 0.69; range, 0.31-6.8 ng mL-1) were detected in all of the non-occupationally exposed adult samples and all of the firefighter samples (DPhP [median, 2.9; range, 0.24-28 ng mL-1], BDCPP [median, 3.4; range, 0.30-44 ng mL-1]); DBzP and DoCP were not detected in any samples.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Hidrocarbonetos Bromados/urina , Organofosfatos/urina , Espectrometria de Massas em Tandem/métodos , Automação , Humanos , Limite de Detecção , Reprodutibilidade dos Testes
3.
Arch Toxicol ; 90(3): 551-7, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25804200

RESUMO

The first withdrawal of certain polybrominated diphenyl ethers flame retardants from the US market occurred in 2004. Since then, use of brominated non-PBDE compounds such as bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (BEH-TEBP) and 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB) in commercial formulations has increased. Assessing human exposure to these chemicals requires identifying metabolites that can potentially serve as their biomarkers of exposure. We administered by gavage a dose of 500 mg/Kg bw of Uniplex FRP-45 (>95 % BEH-TEBP) to nine adult female Sprague-Dawley rats. Using authentic standards and mass spectrometry, we positively identified and quantified 2,3,4,5-tetrabromo benzoic acid (TBBA) and 2,3,4,5-tetrabromo phthalic acid (TBPA) in 24-h urine samples collected 1 day after dosing the rats and in serum at necropsy, 2 days post-exposure. Interestingly, TBBA and TBPA concentrations correlated well (R (2) = 0.92). The levels of TBBA, a known metabolite of EH-TBB, were much higher than the levels of TBPA both in urine and serum. Because Uniplex FRP-45 was technical grade and EH-TBB was present in the formulation, TBBA likely resulted from the metabolism of EH-TBB. Taken together, our data suggest that TBBA and TBPA may serve as biomarkers of exposure to non-PBDE brominated flame retardant mixtures. Additional research can provide useful information to better understand the composition and in vivo toxicokinetics of these commercial mixtures.


Assuntos
Retardadores de Chama/análise , Hidrocarbonetos Bromados/urina , Ácidos Ftálicos/farmacocinética , Ácidos Ftálicos/urina , Animais , Biomarcadores/sangue , Biomarcadores/urina , Exposição Ambiental/análise , Feminino , Retardadores de Chama/farmacocinética , Ácidos Ftálicos/sangue , Ácidos Ftálicos/toxicidade , Ratos Sprague-Dawley
4.
Toxicol Mech Methods ; 22(7): 526-32, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22519856

RESUMO

Three metabolites of 1-bromopropane (1-BP) were measured in urine samples collected from 30 workers exposed to 1-BP at two facilities making furniture seat cushions and evaluated for use as biomarkers of exposure. The mercapturic acid metabolite, N-acetyl-S-(n-propyl)-l-cysteine (AcPrCys), 3-bromopropionic acid (3-BPA), and bromide ion levels (Br(-)) were quantitated for this evaluation. The high exposure group consisted of 13 workers employed as adhesive sprayers who assembled foam cushions using 1-BP containing spray adhesives and the low exposure group consisted of 17 non-sprayers, who worked in various jobs without spraying adhesives. All workers' urine voids were collected over the same 48 h period at work, and at home before bedtime, and upon awakening. Urinary AcPrCys and Br(-) levels were elevated in the sprayers compared to that of non-sprayers. Following HPLC-MS/MS analysis of mercapturic acid metabolite levels, 50 urine samples having the highest levels of AcPrCys were analyzed for 3-BPA. No 3-BPA was detected in any of the samples. The data collected from this study demonstrate that AcPrCys and Br(-) are effective biomarkers of 1-BP exposure, but 3-BPA is not.


Assuntos
Adesivos/farmacocinética , Poluentes Ocupacionais do Ar/urina , Exposição Ocupacional/análise , Adesivos/química , Adulto , Aerossóis , Poluentes Ocupacionais do Ar/química , Biomarcadores/urina , Biotransformação , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Hidrocarbonetos Bromados/química , Hidrocarbonetos Bromados/urina , Masculino , Manufaturas , Estrutura Molecular , Espectrometria de Massas em Tandem , Local de Trabalho/normas
7.
Int J Hyg Environ Health ; 220(2 Pt A): 113-122, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27692573

RESUMO

In this publication the challenges to cope for the aim to obtain innovative biomonitoring methods in our laboratory are visualized for di(2-propylheptyl)phthalate, 2-mercaptobenzothiazole, 3,5-di-tert-butyl-4-hydroxytoluene, 4-nonylphenol, 4-tert-octylphenol, 3-(4-methylbenzylidene)camphor, 4,4'-methylene diphenyl diisocyanate, and Hexabromocyclododecane. For these substances new specific markers were explored based on animal or human kinetic data with urine being the preferred matrix compared to blood. The determination of these markers was complex in all cases, because the sample preparation as well as the detection by high performance liquid chromatography, capillary gas chromatography coupled to tandem mass spectrometers or high resolution mass spectrometry should enable the lowest possible detection limit by use of minimal biological sample volumes. To get a first hint of a possible background level, the analytical methods were applied to urine samples of about 40 persons for each chemical. For Di(2-propylheptyl)phthalate and 2-Mercaptobenzothiazole first results are presented from population biomonitoring.


Assuntos
Monitoramento Ambiental/métodos , Benzotiazóis/urina , Cânfora/análogos & derivados , Cânfora/urina , Poluentes Ambientais/sangue , Poluentes Ambientais/urina , Humanos , Hidrocarbonetos Bromados/urina , Isocianatos/sangue , Fenóis/urina , Ácidos Ftálicos/urina
8.
Toxicol Sci ; 89(2): 380-5, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16280385

RESUMO

2,2',4,4'-Tetrabromodiphenyl ether (BDE 47) is the major polybrominated diphenyl ether (PBDE) found in environmental samples and human tissue despite its small contribution to global production and usage. Currently, three toxicokinetic studies are available investigating single-dose exposures; this is the first study to investigate toxicokinetic parameters following repeated exposure to BDE 47. The disposition and excretion of BDE 47 was monitored in adult female C57BL/6 mice for 5 days following ten consecutive 1.0-mg/kg oral doses and compared with results from our previous study. Results of the present study suggest greater retention of BDE 47 and nonlinear disposition patterns following repeated exposure to this dose in mice. No target tissues of sequestration or potential toxicity were determined; however, some tissues, such as the liver, demonstrated patterns of interest following repeated exposure that were not previously observed in acute toxicokinetic studies. Repeated exposure to BDE 47 results in higher concentrations remaining in adipose tissue, which demonstrates its potential for bioaccumulation. The data also suggest that excretion of BDE 47 may be decreased following repeated exposure. These results, in combination with evidence of its persistence and toxicity, underlie the need to further understand BDE 47 toxicokinetics across species at steady-state conditions.


Assuntos
Hidrocarbonetos Bromados/farmacocinética , Éteres Fenílicos/farmacocinética , Administração Oral , Animais , Citocromo P-450 CYP1A1/biossíntese , Citocromo P-450 CYP2B1/biossíntese , Indução Enzimática , Fezes/química , Feminino , Éteres Difenil Halogenados , Hidrocarbonetos Bromados/sangue , Hidrocarbonetos Bromados/urina , Inativação Metabólica , Camundongos , Camundongos Endogâmicos C57BL , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/enzimologia , Éteres Fenílicos/sangue , Éteres Fenílicos/urina , Bifenil Polibromatos , Distribuição Tecidual
9.
Toxicol Sci ; 90(2): 309-16, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16407092

RESUMO

Despite its minor contribution to global polybrominated diphenyl ether (PBDE) production and usage, 2,2',4,4'-tetrabromodiphenyl ether (BDE 47) is the dominant congener found in most biotic samples in North America. The majority of public health concern has focused on potential hazardous effects resulting from exposure of infants and young children to BDE 47 because of previous studies reporting adverse developmental effects in rodent studies, in combination with human exposure estimates suggesting that nursing infants and young children have the highest exposure to BDE 47. This study was designed with two objectives: (1) to investigate the disposition of BDE 47 in infantile mice reported to be susceptible to BDE 47 and (2) to investigate the disposition and excretion of BDE 47 at various developmental stages in an attempt to further identify the mechanism responsible for rapid urinary excretion. The disposition of (14)C-BDE 47 was monitored in C57BL/6 mice following a single oral dose of BDE 47 (1 mg/kg) at different stages of development. The results show that the toxicokinetics of BDE 47 are different in developing mice than in adult mice; whereas disposition patterns are similar, concentrations of BDE 47 are higher in pups because they have a reduced capacity to excrete BDE 47. These differences lead to higher concentrations of BDE 47 at target tissues during critical windows of development.


Assuntos
Animais Recém-Nascidos/metabolismo , Retardadores de Chama/farmacocinética , Hidrocarbonetos Bromados/farmacocinética , Éteres Fenílicos/farmacocinética , Animais , Poluentes Ambientais/sangue , Poluentes Ambientais/farmacocinética , Poluentes Ambientais/urina , Feminino , Éteres Difenil Halogenados , Hidrocarbonetos Bromados/sangue , Hidrocarbonetos Bromados/urina , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Éteres Fenílicos/sangue , Éteres Fenílicos/urina , Bifenil Polibromatos , Gravidez , Distribuição Tecidual
10.
Artigo em Inglês | MEDLINE | ID: mdl-15607724

RESUMO

A test procedure was developed for the detection and quantification of 1- and 2-bromopropane in human urine. 1-Bromopropane (1-BP) is a commonly used industrial solvent, and 2-bromopropane (2-BP) is often found as an impurity component in industrial grade 1-BP. Both compounds are a health concern for exposed workers due to their chronic toxicity. Bromopropanes have been associated with neurological disorders in both animals and humans. Sample preparation consisted of diluting urine with water and fortification with 1-bromobutane (1-BB), which was used as an internal standard; then each sample was sealed in a headspace vial. A static-headspace sampler (Teledyne-Tekmar Model 7000) was used to heat each sample at 75 degrees C for a 35-min equilibrium time. Quantification was by means of a gas chromatograph (GC) equipped with an electron capture detector (ECD) and a dimethylpolysiloxane (DB-1) capillary column. A recovery study using fortified urine samples at multiple concentrations (0.5-8 microg/ml) demonstrated full recovery; 104-121% recovery was obtained. Precision ranged from 5 to 17% for the 15-20 spiked samples used at each concentration, which were analyzed over multiple experimental trial days. The limit of detection (LOD) for this test procedure was approximately 2 ng/ml 1-BP and 7 ng/ml 2-BP in urine. A recovery study of 1- and 2-BP from fortified urine stored in vials appropriate for field collection was also completed. These results and other factors of the development and validation of this test procedure will be discussed.


Assuntos
Cromatografia Gasosa/métodos , Hidrocarbonetos Bromados/urina , Humanos , Padrões de Referência , Reprodutibilidade dos Testes
11.
Clin Toxicol (Phila) ; 53(8): 823-6, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26161839

RESUMO

BACKGROUND: 1-Bromopropane (1-BP) is an alternative to ozone-depleting solvent that is used in degreasing, dry cleaning, spray adhesives, and aerosol solvents. Occupational exposure to 1-BP is associated with adverse peripheral sensory, motor, and central nervous system (CNS) effects. We report our Health Hazard and Medical Evaluation of 6 patients with neurotoxicity associated with occupational exposure to 1-BP. Case series and environmental evaluation. Six workers, 1 male and 5 female, were exposed to high ambient 1-BP concentrations while employed in a golf club cleaning factory. 1-BP was identified in the bulk solvent sample used by the workers and confirmed the workers' daily occupational exposure to 1-BP for 3-10 months. The major presenting symptoms were tingling pain, soreness in lower extremities, and paresthesia. N-acetyl-S-(n-propyl)-L-cysteine (AcPrCys), a 1-BP metabolite, was identified by LC/MS/MS in the urine (0.171-1.74 mg/g-Cr) of these workers 5-26 days following 1-BP exposure. DISCUSSION AND CONCLUSION: An occupational outbreak of 1-BP poisoning occurred as a result of recurrent power outages, condenser, and exhaust fans malfunction, and inadequate personal protection. Occupational exposure to 1-BP may result in peripheral neuropathy as well as adverse CNS effects. Urine AcPrCys may be a specific biomarker for 1-BP exposure.


Assuntos
Golfe , Síndromes Neurotóxicas/etiologia , Doenças Profissionais/induzido quimicamente , Exposição Ocupacional/efeitos adversos , Solventes/efeitos adversos , Equipamentos Esportivos , Acetilcisteína/análogos & derivados , Acetilcisteína/urina , Adulto , Biomarcadores/urina , Biotransformação , Cromatografia Líquida , Monitoramento Ambiental/métodos , Feminino , Humanos , Hidrocarbonetos Bromados/efeitos adversos , Hidrocarbonetos Bromados/urina , Masculino , Síndromes Neurotóxicas/diagnóstico , Síndromes Neurotóxicas/urina , Doenças Profissionais/diagnóstico , Doenças Profissionais/urina , Saúde Ocupacional , Medição de Risco , Fatores de Risco , Solventes/metabolismo , Espectrometria de Massas em Tandem , Fatores de Tempo , Adulto Jovem
12.
J Chromatogr B Analyt Technol Biomed Life Sci ; 877(8-9): 827-32, 2009 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-19237326

RESUMO

An analytical procedure was developed for the detection and quantification of N-acetyl-S-(n-propyl)-l-cysteine (n-propylmercapturic acid, AcPrCys), a metabolite and biomarker for exposure to 1-bromopropane (1-BP). 1-BP is used as an industrial solvent and exposure is a health concern for industrial workers due to its toxicity. It has been associated with neurological disorders in both animals and humans. Urine sample preparation for the determination of AcPrCys consisted of solid phase extraction (SPE). Urine samples on preconditioned SPE (C18) columns were washed with 40% methanol/60% water solution prior to elution with acetone. Quantification was by means of a liquid chromatograph (LC) equipped with a mass spectrometer (MS) using an Aqua 3 microm C18 300A column and [d(7)]-AcPrCys was used as internal standard. Electrospray ionization (ESI) was used with the MS operated in the negative ion mode and selected ion monitoring (SIM) at m/z 204 for AcPrCys and m/z 211 for [d(7)]-AcPrCys. Demonstrated recovery of urine samples fortified at multiple levels (0.625-10 microg/ml) varied between 96 and 103% of theory with relative standard deviations (RSD) of 6.4% or less. The limit of detection (LOD) for the procedure was approximately 0.01 microg/ml AcPrCys in urine. These data will be discussed as well as other factors of the development of this test procedure.


Assuntos
Acetilcisteína/análogos & derivados , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas/métodos , Acetilcisteína/urina , Humanos , Hidrocarbonetos Bromados/urina
13.
Ann Acad Med Singap ; 38(8): 707-13, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19736576

RESUMO

INTRODUCTION: Methyl bromide is a toxic substance that has hazardous effects on human health with acute and chronic exposure. Our previous study showed that methyl bromide applicators frequently use large amounts of methyl bromide haphazardly in greenhouses in the prefectures of Narlidere and Balcova in the Aegean city of Izmir. This study aims to evaluate the health conditions of these workers. MATERIALS AND METHODS: Our previous study showed that there are 38 methyl bromide applicators in our study area. After the informed consent of methyl bromide applicators was obtained, a questionnaire was used for a survey of demography and symptoms. Each subject was examined before and after application of the compound. Blood and urine samples were collected and stored. Blood samples were analysed for methyl bromide and bromide ion, kidney and liver function tests and lipid profile. RESULTS: The age range of subjects was 19 to 53 years (mean age: 41 +/- 8.57). This study showed that methyl bromide applicators use large amounts of methyl bromide disregarding legal regulations and that some of them had nonspecific complaints. Subjects had been working as methyl bromide applicators for approximately 9.7 +/- 4.15 years. A total of 69.7% of methyl bromide applicators reported that they did not use protective equipment while 33.3% of them had a history of acute methyl bromide intoxication. A statistically significant relationship was found between the usage of protective equipment and the level of blood bromide ion in the blood (P <0.05). CONCLUSION: Usage of methyl bromide, training, screening and follow-up of applicators must be rigorously controlled in accordance with national legal arrangements and international protocols. Greater efforts are required in the implementation of controls to achieve the targets set by the legal regulations and to ensure continual improvement in the limitation of the risks of this environmental hazard.


Assuntos
Jardinagem , Hidrocarbonetos Bromados/toxicidade , Exposição por Inalação/efeitos adversos , Noxas/toxicidade , Doenças Profissionais/induzido quimicamente , Exposição Ocupacional/efeitos adversos , Roupa de Proteção , Adulto , Estudos de Casos e Controles , Feminino , Inquéritos Epidemiológicos , Humanos , Hidrocarbonetos Bromados/sangue , Hidrocarbonetos Bromados/urina , Masculino , Pessoa de Meia-Idade , Noxas/sangue , Noxas/urina , Doenças Profissionais/epidemiologia , Inquéritos e Questionários , Fatores de Tempo , Turquia/epidemiologia
14.
Sangyo Igaku ; 30(1): 54-60, 1988 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-3385989

RESUMO

Methyl bromide has been widely used in Japan to fumigate grains and wood. One death and 3 cases of hospitalization resulted from exposure to methyl bromide at place of residence. These 4 cases were not employed and were members of one family living above a warehouse, the ground level of this building was a warehouse where herbs were stored and the second floor was their living area. On the 13th of May 1978 at 7:00 p.m., the herbs were fumigated with methyl bromide gas. The fumigator used 15 kg of methyl bromide (2 cylinders), a quantity far greater than usual. It is assumed that the concentration in the warehouse was between 10,000-15,000 ppm. Early in the morning on the 16th of May (3 days later), one of the family members, a 12-year-old girl, developed severe convulsions, and later 2 others also had severe convulsions, while the other suffered from marked mental confusion. The serum or plasma bromide ion level ranged from 280 to 600 ppm. The results of the clinical laboratory test showed that GOT exceeded the normal level in 3 out of the 4 cases. Moreover, LDH activity was above the normal range in 3 cases and CPK activity was increased in all the cases.


Assuntos
Habitação , Hidrocarbonetos Bromados/intoxicação , Adulto , Idoso , Gasometria , Exposição Ambiental , Feminino , Humanos , Hidrocarbonetos Bromados/sangue , Hidrocarbonetos Bromados/urina , Masculino , Concentração Máxima Permitida , Pessoa de Meia-Idade , Diálise Renal
15.
J Environ Pathol Toxicol ; 1(5): 543-9, 1978.
Artigo em Inglês | MEDLINE | ID: mdl-722202

RESUMO

Surface tris-(2,3-dibromopropyl) phosphate (TRIS) was removed from flame-retarded polyester fabric by benzene-hexane extraction and replaced with 14C-TRIS. Sections of the radiolabeled fabric (10 X 12 cm) were placed in contact with the clipped skins of rabbits, and urine and feces were collected over a 96 hr period. The cloths were allowed to remain dry or were moistened with either urine or simulated sweat. A similar collection of urine and feces was performed following i.v. injection of 14C-TRIS. From the results of these experiments, it can be calculated that up to 17 percent of the radiolabel on the cloth penetrated rabbit skin over the 96 hr period of exposure. Most of the excreted radiolabel appeared in the urine, with the kidney being the organ of highest specific radioactivity. The highest absorption of radiolabel occurred in the urine-moistened cloth group. Moistening the cloth with simulated sweat produced no increase in absorption over that seen with dry cloth.


Assuntos
Retardadores de Chama/metabolismo , Organofosfatos/metabolismo , Absorção Cutânea , Animais , Vestuário , Feminino , Hidrocarbonetos Bromados/metabolismo , Hidrocarbonetos Bromados/urina , Masculino , Organofosfatos/urina , Coelhos , Suor , Fatores de Tempo , Distribuição Tecidual
16.
Toxicol Appl Pharmacol ; 119(1): 23-33, 1993 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8470121

RESUMO

1,1,2,2-Tetrabromo[U-14C]ethane ([14C]TBE) was used to study the metabolism of TBE in rats. Three graded doses of TBE (1.17, 13.6, and 123 mg/kg; 1 microCi 14C/rat at each dose) were administered by gavage to three groups of four rats each. Excreta samples were collected at various time intervals up to 96 hr. Following euthanization, 14C activity was measured in the excreta, tissues, and carcass. The fraction of the dose exhaled as volatile metabolites of TBE, excluding 14CO2, was approximately 9-10% higher in rats given the high dose of TBE compared to that in rats given either the low or the medium dose. The fraction excreted in the urine decreased with increasing TBE dosage. 1,2-Dibromoethylene and tribromoethylene were identified as exhaled metabolites at the high dose. Three major urinary metabolites were identified: dibromoacetic acid, glyoxylic acid, and oxalic acid. The results of this study indicate that the metabolism of TBE was linear up to a dose of 13.6 mg/kg, but the contribution of various TBE metabolic pathways was different at a dose of 123 mg/kg.


Assuntos
Hidrocarbonetos Bromados/metabolismo , Acetatos , Administração Oral , Animais , Cloroacetatos , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Fezes/química , Cromatografia Gasosa-Espectrometria de Massas , Glioxilatos/urina , Hidrocarbonetos Bromados/administração & dosagem , Hidrocarbonetos Bromados/toxicidade , Hidrocarbonetos Bromados/urina , Masculino , Oxalatos/urina , Ácido Oxálico , Ratos , Ratos Endogâmicos F344 , Ácido Tricloroacético/urina
18.
Toxicol Appl Pharmacol ; 158(2): 103-14, 1999 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-10406925

RESUMO

Chloro, bromo, and mixed bromochloro haloacetates (HAs) are by-products of drinking water disinfection and are hepatocarcinogenic in rodents. We compared the toxicokinetics of a series of di-HAs, dichloro (DCA), bromochloro (BCA), dibromo (DBA) and tri-HAs: trichloro (TCA), bromodichloro (BDCA), chlorodibromo (CDBA), and tribromo (TBA) after iv and oral dosing (500 micrometer/kg) in male F344 rats. The blood concentrations of the HAs after iv injection declined in a bi-exponential manner with a short but pronounced distributive phase. The structural features that had the greatest influence on the disposition of HAs were substitution of a halogen for a hydrogen and the degree of bromine substitution. All di-HAs had blood elimination half-lives of less than 4 h (DCA > DBA, BCA) compared to the tri-HAs, which had half-lives that varied from 0.6 to 8.0 h (TCA > BDCA > CDBA > TBA). The urinary excretion of all di-HAs was low and accounted for less than 3% of the dose in contrast to the tri-HAs, where urinary excretion accounted for at least 30% of the dose. Toxicokinetic analysis indicated the steady-state apparent volume of distribution varied between 301 and 881 ml/kg among the HAs, but the variation was not statistically significant (P > 0.17). The blood concentration-time profiles for all di-HAs after oral dosing was complex and exhibited multiple peaks. This did not appear to be due to enterohepatic recirculation, as bile duct cannulated animals also displayed similar profiles. In contrast, the profiles for the tri-HAs did not exhibit multiple peaking after oral dosing and could be described using a one-compartment pharmacokinetic model. The oral bioavailability of the HAs varied between 30% (DBA) and 116% (TCA), depending on the number of halogen substituents and the degree of bromine substitution. In general, three patterns of elimination for the HAs can be broadly described: low metabolism with moderate renal clearance (TCA), high metabolism and renal clearance (BDCA, CDBA, TBA), and high metabolism, low renal clearance (DCA, BCA, DBA).


Assuntos
Acetatos/farmacocinética , Ácidos/farmacocinética , Hidrocarbonetos Bromados/farmacocinética , Hidrocarbonetos Clorados/farmacocinética , Acetatos/sangue , Acetatos/urina , Ácidos/sangue , Ácidos/urina , Administração Oral , Animais , Disponibilidade Biológica , Meia-Vida , Hidrocarbonetos Bromados/sangue , Hidrocarbonetos Bromados/urina , Hidrocarbonetos Clorados/sangue , Hidrocarbonetos Clorados/urina , Infusões Intravenosas , Masculino , Ligação Proteica , Ratos , Ratos Endogâmicos F344 , Relação Estrutura-Atividade , Distribuição Tecidual
19.
Toxicol Appl Pharmacol ; 78(2): 215-25, 1985 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-4035677

RESUMO

Methyl bromide is a widely used soil fumigant and poses potential inhalation hazard to workers. Uptake of methyl bromide and pathways for excretion of 14C were investigated in male Fischer-344 rats after nose-only inhalation of 50, 300, 5700, or 10,400 nmol (1.6 to 310 ppm) of [14C]methyl bromide/liter of air for 6 hr. Fractional uptake of methyl bromide decreased at the highest concentrations, 5700 and 10400 nmol/liter, with 37 and 27% of the inhaled methyl bromide absorbed, respectively, compared to 48% at the lower levels. This resulted in the same total amount of methyl bromide being absorbed at the two higher exposure concentrations (650 mumol/kg body wt). Total methyl bromide adsorbed was 9 or 40 mumol/kg body wt after exposure to 50 or 300 nmol/liter, respectively. Elimination of 14C was linearly related to the amount of methyl bromide absorbed as determined from urine, feces, expired CO2, and parent compound collected for 66 hr after the end of exposure. Exhaled 14CO2 was the dominant route of excretion, with from 1.2 to 110 mumol (50% of amount absorbed) exhaled, and was described by a two-component negative exponential function; 85% was exhaled with a t 1/2 of 4 hr, and the remaining 15% was exhaled with a t 1/2 of 17 hr. The rate of exhalation of 14CO2 was not affected by the amount of [14C]methyl bromide absorbed. From 0.4 to 54 mumol was excreted in urine (20% of amount absorbed). The half-time for excretion of 14C in urine was approximately 10 hr, and the rate of excretion was not dependent on the amount of [14C]methyl bromide absorbed. Little 14C was exhaled as methyl bromide (less than 4% of the dose) or excreted in feces (less than 2%). At the end of 66 hr, 25% of the 14C absorbed remained in the rats. Liver, kidneys, adrenals, lungs, thymus, and turbinates (maxilloturbinates, ethmoturbinates, and nasal epithelial membrane) contained the highest concentrations of 14C. Results indicated that uptake of inhaled methyl bromide could be saturated. Any [14C]methyl bromide equivalents absorbed, however, would be excreted by concentration-independent mechanisms.


Assuntos
Poluentes Ocupacionais do Ar/toxicidade , Hidrocarbonetos Bromados/metabolismo , Animais , Relação Dose-Resposta a Droga , Meia-Vida , Hidrocarbonetos Bromados/toxicidade , Hidrocarbonetos Bromados/urina , Cinética , Masculino , Modelos Biológicos , Ratos , Ratos Endogâmicos F344 , Respiração/efeitos dos fármacos , Sistema Respiratório/metabolismo , Distribuição Tecidual
20.
Bull Environ Contam Toxicol ; 15(2): 192-7, 1976 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-943192

RESUMO

An investigation was made of the possible migration of a flame retardant, tris (2,3-dibromopropyl) phosphate (TBPP), commercially used in childrens sleepwear, to the skin of rats and humans and subsequent absorption. When the pure chemical was applied directly to the shaved skin of a rat, the hydrolysis product, 2,3-dibromopropanol (DBP), appeared in the urine. The 10,000 X g supernatant fraction of rat liver hydrolyzed TBPP to DBP. When TBPP-finished fabrics were worn by a rat, an adult male and a 5-year-old boy for up to 9 days, DBP was not detected in the urine.


Assuntos
Vestuário , Organofosfatos/metabolismo , Animais , Pré-Escolar , Cromatografia Gasosa , Humanos , Hidrocarbonetos Bromados/metabolismo , Hidrocarbonetos Bromados/urina , Técnicas In Vitro , Masculino , Microssomos Hepáticos/metabolismo , Organofosfatos/urina , Ratos , Absorção Cutânea
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