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1.
4,4'-Methylenebis (2-chloroaniline): an unregulated carcinogen   总被引:1,自引:0,他引:1  
4,4'-Methylenebis (2-chloroaniline) (MBOCA) is a confirmed animal carcinogen. It is used commercially as a curing agent for polymers containing isocyanate. There are no adequate studies documenting a carcinogenic risk for MBOCA in humans; however, studies in rats and dogs have shown that MBOCA is a carcinogen. Also, MBOCA is structurally similar to aromatic amines, which cause bladder cancer in workers with occupational exposure. Manufacture of MBOCA in the United States ceased in 1979. However, estimates of the number of workers potentially exposed range from 1,400 to 33,000 in the manufacture of MBOCA-cured products. Presently, there are no federal regulations limiting occupational exposure to MBOCA. An occupational standard for MBOCA proposed by the Occupational Safety and Health Administration was remanded by the Third Circuit Court of Appeals on procedural grounds in 1974. NIOSH recommended in 1978 that MBOCA be treated as a potential human carcinogen and that worker exposure be controlled so that it does not exceed 3 micrograms/m3 of air determined as a time-weighted average concentration for up to a 10-hour workshift (the lowest level that can be reliably measured). In this paper, we will review the literature in regard to MBOCA's carcinogenicity, describe industrial use and extent of worker exposure, and review MBOCA's status in relation to occupational regulations in the United States and abroad.  相似文献   

2.
A biological monitoring programme has been developed for assessing occupational exposure to 4,4'-methylenebis (2-chloroaniline) (MBOCA) in a factory which manufactures polyurethane elastomers. In a systematic programme of biological monitoring over a five year period urinary MBOCA concentrations have been used to provide evidence of absorption of MBOCA. Improvements in the handling and use of MBOCA have coincided with a steady reduction in the urinary MBOCA concentrations.  相似文献   

3.
A biological monitoring programme has been developed for assessing occupational exposure to 4,4'-methylenebis (2-chloroaniline) (MBOCA) in a factory which manufactures polyurethane elastomers. In a systematic programme of biological monitoring over a five year period urinary MBOCA concentrations have been used to provide evidence of absorption of MBOCA. Improvements in the handling and use of MBOCA have coincided with a steady reduction in the urinary MBOCA concentrations.  相似文献   

4.
4,4'-methylene-bis-ortho-chloro-aniline (MBOCA) is an aromatic amine and industrial chemical that has been shown to cause cancer of several different organs in rats and mice and bladder cancer in dogs. The purpose of this study was to determine the efficacy of using urinary concentrations of MBOCA as a means for evaluating extent of exposure. Male Sprague-Dawley rats were given MBOCA and [14C]MBOCA by either gavage or skin application. Concentrations and amounts of 14C were measured in urine, feces, skin and total carcasses, and parent MBOCA in urine at several intervals after application. The percentages of administered doses excreted and retained in the animals were calculated and comparisons made. Within 72 hr after gavage 16.5% of the administered compound was excreted in urine as 14C but only 0.25% as parent MBOCA. In the same interval after skin application a maximum of 2.54% of administered MBOCA was excreted as 14C but only 0.008% as parent MBOCA. Seventy-two hours after gavage 13.7% of the administered dose was retained in the tissues, and after skin absorption 5–13% was retained. With gavage the rate of excretion of 14C in urine and feces was very high in the first 24 hr (68.3%) but fell off rapidly (2.07%) by the third day. After skin absorption the rates of excretion of 14C were fairly constant over a 3-day period. Less MBOCA was absorbed from the skin if the skin was washed within 8 hr after application, as compared to waiting 24 hr or not washing at all. The amount of parent MBOCA detected in urine is a very small amount of that applied or absorbed. The percentage detected and the rates of excretion depend upon the route of administration, and the interval between exposure and sampling. For these reasons urinary analysis for MBOCA can be used only as very imprecise indicators of extent of recent exposure.  相似文献   

5.
Oxidative DNA damage may play an important role in the human carcinogenic process. Recently, we reported a case of bladder cancer among 4, 4'-methylenebis (2-chloroaniline) (MBOCA)-exposed workers. By measuring the plasma level of 8-hydroxydeoxyguanosine (8-OHdG), we investigated the association between oxidative DNA damage and MBOCA exposure. In addition, we examined the effects of different confounders on the plasma level of 8-OHdG. We undertook a cross-sectional survey at four MBOCA-producing factories in Taiwan (158 subjects). Plasma 8-OHdG levels and urinary MBOCA concentrations were measured by liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS). Personal characteristics were collected by questionnaire. The workers were classified according to their job titles as exposed (n=57) or unexposed (n=101) groups as well as classified according to urinary MBOCA levels as high urinary MBOCA (>20 microg/g creatinine) (n=45) or low urinary MBOCA (n=108) groups. Neither the MBOCA-exposed workers nor the high urinary MBOCA workers had a significant increase in the mean plasma 8-OHdG level, even after adjustment for potential confounders. Age and gender were significantly positively correlated with plasma 8-OHdG levels. Smokers among high urinary MBOCA workers also had significantly higher 8-OHdG levels than non-smokers among high urinary MBOCA workers. Our study provides evidence that smoking rather than MBOCA exposure induces elevation of plasma 8-OHdG levels among workers exposed to MBOCA, indicating that oxidative DNA damage does not play an important role in the carcinogenic processes of MBOCA.  相似文献   

6.
A 52-year-old male chemical worker was admitted to the hospital with a history of paroxysmal microscopic hematuria for about 2 years and nocturia with gross hematuria about five times per night for 2 months. He was a nonsmoker and denied a history of any other bladder carcinogen exposure except for occasional pesticide application during agricultural work. Intravenous urogram imaging showed a mass occupying half of the bladder capacity. Cystoscopy revealed a mass over the left dome of the bladder. Cystoscopic biopsy revealed a grade 3 invasive transitional cell carcinoma with marked necrosis. From 1987 until hospital admission in 2001, the patient had worked in a company that produced the 4,4 -methylenebis(2-chloroaniline) (MBOCA) curing agent. He did not wear any personal protective equipment during work. Ambient air MBOCA levels in the purification process area (0.23-0.41 mg/m3) exceeded the U.S. Occupational Safety and Health Administration's permissible exposure level. Urinary MBOCA levels (267.9-15701.1 microg/g creatinine) far exceeded the California Occupational Safety and Health Administration's reference value of 100 microg/L. This patient worked in the purification process with occupational exposure to MBOCA for 14 years. According to the environmental and biologic monitoring data and latency period, and excluding other potential bladder carcinogen exposure, this worker was diagnosed as having occupational bladder cancer due to high exposure to MBOCA through inhalation or dermal absorption in the purification area. This case finding supports that MBOCA is a potential human carcinogen. Safe use of skin-protective equipment and respirators is required to prevent workers from MBOCA exposure.  相似文献   

7.
Absorption of 4,4'-methylenebis (2-chloroaniline) (MBOCA) was assessed for five workers over one week in a polyurethane elastomer factory by measuring urinary MBOCA levels by high performance liquid chromatography (HPLC) using an electrochemical detector. Personal air exposure levels of MBOCA ranged from 0.2 to 8.9 micrograms/m3. The mean urinary MBOCA levels at the beginning and the end of the work shift were 3.1-81.5 and 2.4-96.6 micrograms/g creatinine, respectively. The differences between preshift and postshift urinary MBOCA values were not significant in all workers, according to the paired t-test. The urinary levels after a two-day holiday (on Monday morning) were almost equal to those of preshift levels on other weekdays. Urinary excretion of MBOCA was much higher than the estimated MBOCA levels from personal exposure measurements, suggesting that a significant amount of MBOCA is absorbed by routes other than inhalation. These results lend strong support for the need to monitor exposure control by urinary MBOCA measurement.  相似文献   

8.
OBJECTIVE--To conduct a field study to obtain information on the urinary concentrations of aluminium (Al) and fluoride (F-) depending on the different compounds exposed to in the aluminum industry. METHODS--16 workers from one plant that produced aluminium fluoride (AlF3), and from two plants that produced aluminium electrolytically by two different processes participated in the study for one working week. Pollutants were monitored by eight hour personal sampling every day, and urine samples were collected during the week. Al and F- were analysed in both atmospheric and urine samples by atomic absorption spectrometry and an ion selective electrode. RESULTS--The principal results show different characteristics of kinetic curves of Al and F- excretion in workers with different exposures. Some characteristics of excretory peaks were linked to specific exposures--for instance, after exposure to AlF3 there was one delayed Al peak associated with one delayed F- peak about eight hours after the end of the daily shift, and after mixed exposure to HF and AlF3, two F- peaks were noted, one fast peak at the end of the shift and another delayed peak at 10 hours synchronised with an Al peak. In one of the electrolysis plants, the exposure to Al and F- compounds led to the simultaneous excretion of Al and F- peaks, either as a single peak or two individual ones depending on the type of technology used on site (open or enclosed potlines). The average estimated half life of Al was 7.5 hours, and of F- about nine hours. Quantitative relations between excretion and exposure showed an association between the F- atmospheric limit value of 2.5 mg/m3 with a urinary F- concentration of 6.4 mg/g creatinine at the end of the shift, a peak of 7.4 mg/g creatinine, and 7.4 mg excreted a day. For Al, the exposure to 1.36 mg/m3 during the shift corresponded to a urinary concentration at the end of the shift of 200 microgram/g creatinine. Daily excretion of 200 micrograms corresponded to an exposure to 0.28 mg/m3. CONCLUSION--Particular differences in the behaviour of Al and F- in urine depended upon the original molecular form in the pollutant. These results reinforce the principle that, in biological monitoring, the sampling strategy and the choice of limit value should be dependent on kinetic data that take the exposure compound of the element in question into account.  相似文献   

9.
对32名职业接触甲苯、18名志愿受试者和77名非职业接触甲苯者的尿中马尿酸及邻甲酚的测定,发现在非接触者中,尿中马尿酸存在日间波动,邻甲酚排出量极少。工人和志愿者接触甲苯后,尿中马尿酸即开始上升,到脱离时达高峰,以后迅速下降,4小时左右降到正常本底水平,班末尿中马尿酸浓度与空气浓度相关(工人:r=0.64,志愿者:r=0.78)。尿中邻甲酚在低浓度接触者中,难以检出,但在高浓度接触时,班末尿中邻甲酚与空气浓度相关(工人;r=0.63,志愿者;r=0.65)。马尿酸和邻甲酚作为甲苯生物监测指标可结合使用。  相似文献   

10.
MBOCA (4,4′ methylenebis (2-chloroaniline) is a structural analogue of benzidine and is carcinogenic in mice, rats, and dogs. MBOCA has not yet been demonstrated to be carcinogenic in humans and is not regulated as an occupational carcinogen in the United States. We report two noninvasive papillary tumors of the bladder identified in a screening study of 540 workers exposed to MBOCA during its production at a Michigan chemical plant from 1968 to 1979. Both tumors occurred in men under 30 years old who had never smoked. Although the prevalence of grade 1-2 tumors among asymptomatic males in this age group is unknown, the incidence of clinically apparent tumors on U.S. males aged 25-29 is only 1 per 100,000 per year. The detection of the two tumors in young, nonsmoking males is consistent with the hypothesis that MBOCA induces bladder neoplasms in humans.  相似文献   

11.
Percutaneous (pc) absorption, disposition, and excretion of 14C-MBOCA (4,4'-methylenebis(2-chloroaniline) ) were investigated in male beagle-type dogs by HPLC and compared to intravenously (iv) administered controls. Following application of 115 muCi MBOCA to a 25 cm2 area of the skin, no measurable radioactivity was detected in blood for the subsequent 24-hr period, but 14C-MBOCA and metabolites were excreted in urine and bile. During the 24-hr collection period, a total of 1.3% of the administered dose was recovered in the urine (0.4% of which was unchanged MBOCA). At 24 hr 0.62% of the dose was recovered in gallbladder bile. Approximately 90% of the administered dose was recovered in skin at the application site. Liver, kidney, and fat were the tissues with highest radioactivity. After a bolus iv injection, MBOCA disappeared rapidly from blood (t 1/2 beta = 0.70 hr). In the 24 hr following iv injection, 46% of the administered dose was excreted in urine (0.54% of which was unchanged MBOCA). At 24 hr 32% of the dose was recovered in gallbladder bile. Tissue radioactivity was 10-20 X higher after iv than pc administration and highest in liver, kidney, fat, and lung. The results demonstrated in a canine model that skin absorption was a viable route of entry for MBOCA and that unmetabolized MBOCA was a small percentage (0.4-0.5%) of the total urinary excretion. MBOCA was rapidly and extensively metabolized and excreted in urine and bile following both iv and pc administration.  相似文献   

12.
There are few studies on phenylisocyanate (PhI) exposure, although there are studies indicating that PhI is a very potent chemical sensitizer. The aim of this study was to evaluate aniline in urine and plasma as possible biomarkers of exposure to PhI. Occupational airborne exposure to PhI was measured during one day for 11 workers exposed to thermal degradation products from polyurethane with filters impregnated with 2-methoxyphenyl piperazine. A urine sample was collected from each worker on measurement day, and plasma samples were collected within the following 2 weeks. Urine and plasma samples also were collected from four unexposed subjects. The biological samples were hydrolyzed and analyzed with gas chromatography mass spectrometry. The time-weighted averages (TWA) for the workers were between 0.1 and 1.6 microg/m3. Aniline levels in urine were in the same range for the exposed and unexposed workers, but there was a significant correlation between air and urinary levels (Pearson's correlation coefficient r = 0.518; p = 0.05). All exposed workers had higher levels in the plasma samples than the highest control, and there was a significant correlation between the plasma levels and measured air levels (r = 0.675; p = 0.008). The conclusion is that aniline in hydrolyzed urine and plasma are possible biomarkers of exposure to PhI, and that the plasma biomarker is more sensitive, at least at this rather low exposure.  相似文献   

13.
The objectives of this research were to improve and standardize a relatively easy, highly sensitive and highly accurate method of measuring nicotine, cotinine and trans-3'-hydroxycotinine in the urine of non-smokers exposed to environmental tobacco smoke (ETS) and to clarify the reliability of this method. Blinded studies using this analytical method were conducted in two universities. Standard solutions of nicotine, cotinine and trans-3'-hydroxycotinine were prepared at one university, divided in two parts and sent to another two universities for analyses by gas chromatography-mass spectrometry (GC/MS) without revealing the concentrations. It was found that the assay lower limit was at a level that could be used in passive smoking surveys and good results were obtained in crosschecks of samples of unknown concentration between the two universities. Since this method was considered to be useful for analyzing these urinary substances, ETS exposure experiments were performed in three universities using urinary nicotine, cotinine and trans-3'-hydroxycotinine as specific biomarkers of the urine. Non-smokers were exposed to ETS in an exposure room in each university. It was found that the nicotine concentrations in the urine of the subjects exposed to ETS reached a peak at about 2 hours after the end of exposure, which was somewhat later than that in active smokers. Because cotinine and trans-3'-hydroxycotinine in the urine are metabolites of nicotine, it was evident that the quantities were lower and the increasing rates were also less than that of nicotine. When the deceases in nicotine/ creatinine, cotinine/creatinine and trans-3'-hydroxycotinine/creatinine ratios in the urine were calculated using theoretical curves, the half-life times were calculated to be 13.9, 20.0 and 63.0 hours, respectively.  相似文献   

14.
A two-year study of the occupational exposure of workers in a lumber mill to a wood preservative containing chlorophenol has been conducted. The methods were biological (urine) monitoring, industrial hygiene assessment and a questionnaire related to worker-perceived health effects. Approximately 40 workers exposed to the wood preservative and 40 unexposed controls working in other locations of the plant participated in the study. Evaluation of work conditions, assessment of urinary levels of tetra- and pentachlorophenol, and administration of a medical questionnaire were performed at a six-month intervals over a two-year period. Industrial hygiene ratings of exposures and adequacy of protection were evaluated in relation to the results of biological monitoring. Workers who came into contact with freshly treated and still wet wood had consistently higher urinary levels of tetrachlorophenol. Workers stationed adjacent to the spray applicator also had higher tetrachlorophenol levels. There was no statistically significant relationship between the subjective ratings by the industrial hygienist of exposure and adequacy of worker protection with the urinary levels of tetrachlorophenol. Nor was there a consistent pattern linking exposure ratings with adequacy of protection. The short half-life of tetrachlorophenol in the urine makes this a good indicator of only the most recent exposure. The differences in urinary levels between controls and exposed workers were large, with averages of 240.4 ppb for exposed workers and 14.6 for controls. Traditional industrial hygiene evaluation techniques, in conjunction with biological monitoring, proved to be the most effective method of assessing both exposure and work practices. Exposed workers reported a statistically significant increase of positive answers to known signs and symptoms of chlorophenol exposure compared with the controls. There was no statistically significant relationship between the number of these health problems reported and the mean urinary levels of tetra- or pentachlorophenol for the exposed group; however, for certain variables (heavy vs. light exposure, inadequate vs. adequate protection, greater than 100 ppb urinary tetrachlorophenol vs. less than 100 ppb), those with heavier exposure, inadequate protection or higher urinary tetrachlorophenol reported on the average more health problems over the two-year period. Firm statistical conclusions could not be drawn because of the small size of the study population.  相似文献   

15.
Workers in plants producing carbon anodes for aluminium electrolysis are exposed to PAHs containing coal tar pitch volatiles, pitch and coke. The aim of this study was to evaluate the suitability of urinary 1-hydroxypyrene to characterize respiratory exposure to PAH, which is most relevant for assessing individual health risks. Six workers in a carbon anode plant volunteered to take part in a personal air sampling and a biological monitoring programme lasting five consecutive 8-h shifts to determine occupational exposure to airborne PAHs and urinary excretion of 1-hydroxypyrene. Exposure to total PAH for all worksites varied from 3.99 to 120.6 μg PAH m−3 and for benzo(a)pyrene (BaP) from 0.17 to 4.88 μg BaP m−3. The concentration of 1-hydroxypyrene in post- and pre-shift urine samples was in the range (0.5–61.8 μmol 1-OHP per mol creatinine) and depended on the worksite. The Spearman rank correlation test showed a low but significant (P < 0.05) correlation of urinary 1-hydroxypyrene in the post- and pre-shift samples with respiratory pyrene exposure. The quantitative aspects of biological monitoring for the evaluation of respiratory PAH exposure were tested with a pharmacokinetic model. On the basis of individual pyrene exposure, excretion of urinary 1-hydroxypyrene during the working week was calculated for each worker. The results presented in this investigation indicate that biological monitoring of the pyrene metabolite 1-hydroxypyrene is a useful indicator of a general PAH exposure, but cannot replace personal air sampling for assessing the lung cancer risk of individuals.  相似文献   

16.
Experimental study on the metabolism of triethylamine in man.   总被引:4,自引:3,他引:1       下载免费PDF全文
Five healthy volunteers were exposed by inhalation to triethylamine (TEA; four or eight hours at about 10, 20, 35, and 50 mg/m3), a compound widely used as a curing agent in polyurethane systems. Analysis of plasma and urine showed that an average of 24% of the TEA was biotransformed into triethylamine-N-oxide (TEAO) but with a wide interindividual variation (15-36%). The TEA and TEAO were quantitatively eliminated in the urine. The plasma and urinary concentrations of TEA and TEAO decreased rapidly after the end of exposure (average half time of TEA was 3.2 h). There was an excellent association between air levels of TEA and the urinary concentrations in samples obtained within two hours of the end of exposure. Thus the urinary level of TEA taken in this period is useful as a biological monitoring of exposure. An air concentration of 10 mg/m3 corresponds to an average urinary concentration of about 40 mmol/mol creatinine (at sedentary work).  相似文献   

17.
Objective This study was undertaken to estimate the absorbed doses of carbaryl and the associated health risks in a group of horticultural greenhouse workers in the Province of Quebec, Canada, using a toxicokinetic modeling approach. Methods A mathematical model was developed to relate the absorbed dose of carbaryl, the evolution of its body burden and that of its metabolites and the urinary excretion rate of biomarkers. The free parameters of this model were determined using published time course data in volunteers exposed to carbaryl under controlled conditions. The model was used to determine cumulative urinary amounts of 1-naphthol that would be excreted by a typical worker exposed to a pre-established no-observed-adverse-effect level (NOAEL) dose; this biomarker amount was then taken as a biological reference value below which the risks of health effects were considered negligible. As a measure of the applicability of this approach to practical situations, the model was used to estimate the dose of carbaryl absorbed by each greenhouse worker, starting from his/her cumulative urinary excretion time courses of 1-naphthol over a 24-h period following the onset of a work exposure. Their cumulative 1-naphthol levels were then compared to the biological reference value obtained from the model and the NOAEL dose. Results Following the onset of a work exposure to carbaryl, a clear increase in the urinary excretion rate of 1-naphthol was observed in most workers. The reconstructed absorbed doses were found to vary between 3.3 and 143 nmol/kg of body weight (bw) depending on the working conditions. Simulations of the observed cumulative urinary excretion time course of each worker also showed that exposure appeared to occur mainly (a) through inhalation for the applicators and individuals without direct contact with treated plants and (b) through the dermal route for individuals manipulating treated plants. Although the workers under study clearly appeared to have been exposed to carbaryl in the greenhouses, 24-h cumulative 1-naphthol levels ranged from 4.8 to 65.1% of the proposed biological reference value of 32 nmol/kg bw in 24-h urine collections following the onset of a work exposure. Conclusion This suggests that the workers under study probably did not incur a serious health risk under the normal exposure conditions prevailing during the study period.  相似文献   

18.
4,4-Methylene-bis-(2-chloroaniline), (MBOCA) is a suspected human carcinogen. Recently a massive contamination case by this compound was uncovered in Adrian, Michigan. By using two microbial strains,Bacillus megaterium and aNocardiopsis sp., it was determined that MBOCA is rapidly degraded. The major route of metabolism in these microorganisms is through Nacetylation and N-hydroxylation. The identities of the major metabolic products were established via mass spectroscopic analyses. These metabolites are also suspected mutagens.  相似文献   

19.
The validity of urinary nicotine and its metabolites as a biomarker of exposure to environmental tobacco smoke (ETS) has been investigated. After exposure to ETS, urine samples were collected from 10 subjects for the analyses of nicotine, cotinine and 3'-hydroxycotinine. The former two chemicals were detected in the urine of all subjects, and 3'-hydroxycotinine was detected in the urine of 9 subjects out of 10, indicating these three chemicals can be used as a biomarker of ETS exposure. 3'-Hydroxycotinine was not detected in the urine of one subject, suggesting that this subject may be a poor metabolizer of nicotine. In 9 subjects with 3'-hydroxycotinine excreted, the amounts of nicotine and cotinine started to increase after exposure, reached the peak at the end of the second exposure and decreased gradually. 3'-Hydroxycotinine started to be excreted into urine from 3 hours after exposure and kept the same level until 72 hours after exposure. In the urine of 72 hours after exposure, the amount of 3'-hydroxycotinine was the highest among these three chemicals.  相似文献   

20.
饮酒对尿2 -硫代噻唑烷-4-羧酸排泄的影响   总被引:1,自引:1,他引:0  
目的观察饮酒对二硫化碳(CS2)接触者及非接触者尿2-硫代噻唑烷4羧酸(TTCA)排泄的影响。方法(1)男性非接触CS2志愿者10人,一次饮用38。白酒150ml或250ml,高效液相色谱法观察其尿TTCA排泄动态;(2)CS2作业男工152人,非接触者60人,分别收集班末尿和晨尿进行TTCA测定并进行问卷调查;同时进行个体空气采样和CS2浓度气相色谱法测定。结果非接触者一次饮白酒150ml后3h尿TTCA水平达峰值,12h后降至饮前水平(餐前0.5h,饮酒后1、3、12h中位数分别为0.045、0.068、0.099、0.046mg/gCr,n=10);TTCA水平随饮白酒剂量的增加而增高,饮0、150、250ml白酒者TTCA水平(中位数)分别为0.036、0.064、0.609mg/gCr(n=5,饮后3h)。CS2浓度为≤10.0、10.1~50.0、>50.0mg/m3时,CS2接触者TTCA有随CS2浓度增高而上升的趋势;对照组中饮白酒和啤酒者TTCA水平似高于不饮者,而接触组TTCA水平则随饮酒指数的增加而呈降低趋势。结论大量饮酒可影响尿TTCA水平,在进行CS2生物监测时,应避免在大量饮酒后12h内采集尿样,以避免饮酒对监测结果的干扰作用。  相似文献   

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