Urinary excretion of 1-pyrenol in automotive repair workers

Summary The urinary excretion of a pyrene metabolite was evaluated in 65 automotive repair workers whose skin was exposed to used mineral oils, and in 41 controls. Pyrene contents were determined in oily material taken from cloths used to clean various types of engines (n = 8) and were found to vary (mean ± SD) from 2.8 ± 0.4 ppm for dirty matter obtained from diesel truck engines to 9.3 ± 8.2 ppm for that from petrol car engines. Tobacco smoking and polycyclic aromatic hydrocarbon (PAH)-rich diets were considered as confounding factors. At both the beginning and the end of the working week, the values of urinary 1-pyrenol were slightly higher in exposed subjects (0.178 ± 0.150 and 0.194 ± 0.135 mol/mol creatinine on Monday and Friday, respectively) than in controls (0.124 ± 0.090 mol/mol creatinine) (Mann-Whitney test, z = 2.741, P < 0.01). The urinary 1-pyrenol values were higher in both smoking and non-smoking subjects than in controls. The highest values were found in urinary samples of smokers exposed to used mineral oils (0.259 ±0.201 mol/mol creatinine). In non-smoking workers (n = 40), post-shift 1-pyrenol values were 0.154 ± 0.105 ol/mol creatinine, as against 0.083 ± 0.042 mol/mol creatinine for the 19 non-smoking controls (Mann-Whitney test, z = 2.765, P < 0.01). In automobile repair workers, urinary 1-pyrenol values before the beginning of the weekly workshift did not differ substantially from those measured at the end of the week, not being related to the subjective degree of dirty skin as stated by workers. Multiple regression analysis between urinary metabolite levels and the three independent variables turned out to be statistically significant (r ² = 0.295, 0.246; F-test = 14.2, 11.1; P both < 0.01) for Monday and Friday urinary metabolite values and revealed that tobacco smoking had a greater influence (contribution to r ² = 16.1% and 18.3% on Monday and Friday, respectively) than occupational exposure (3.8% and 6.6%, respectively) on urinary levels of 1-pyrenol; the influence of PAH-rich foods on urinary pyrene metabolite levels was only detectable when subjects returned to work after the weekend (5.5%).Comparison between urinary excretion of 1-pyrenol in this group of workers and that found in professionally exposed subjects indicates that exposure to PAHs through contamination of the skin with used engine oil during automotive repair work is very low.     

Biological monitoring of human exposure to coal tar

Summary Three methods for the biological monitoring of human exposure to coal tar were compared. Levels of 1-hydroxypyrene(1-OH PYR), polycyclic aromatic hydrocarbons (PAH) and mutagens (Ames plate incorporation assay using Salmonella typhimurium strain TA98 in the presence of S9 and -glucuronidase) were determined in urinary samples from psoriatic patients undergoing topical treatment with mineral coal tar. A single sample of urine with a high content of PAH was diluted with urine of non-exposed, non-smoking subjects in order to obtain nine samples with a decreasing content of PAH metabolites. Mutagenicity of the extracts was detectable down to the dilution corresponding to a content in 1-OH PYR of about 50 g/g creatinine and total PAH of 7 g/g creatinine. In a second phase the three indicators of exposure to PAH were compared in 16 urinary samples from four psoriatic patients. The total PAH levels determined by the acidic deconjugation/reduction method were confirmed to be nearly always lower than the corresponding levels of 1-OH PYR alone. Most of the extracts were mutagenic, however, some of the samples with a high content in PAH metabolites were not mutagenic. In all the urinary samples analyzed the excretion of 1-OH PYR was markedly greater than in control subjects. 1-OH PYR and urinary mutagenicity levels were well correlated. The present data suggest that both the determination of mutagenicity and 1-OH PYR in urine may be used to monitor occupational exposure to PAH, the latter method being cheaper and of greater specificity and sensitivity.     

1-Hydroxypyrene in human urine after exposure to coal tar and a coal tar derived product

Summary A method for isolating 1-hydroxypyrene from urine is described. The presence of 1-hydroxypyrene in urine was identified by fluorescence excitation and emission scanning after HPLC-separation. 1-Hydroxypyrene could be detected in the urine of rats following oral administration of as little as 0.5 g pyrene. The dose-dependence of 1-hydroxypyrene in urine was evident after a wide range of pyrene dosing. After therapeutical coal tar treatment of dermatological patients the enhanced excretion of 1-hydroxypyrene was highly significant. Employees of a creosote impregnating plant showed an excretion pattern of 1-hydroxypyrene which could be related to their work. 1-Hydroxypyrene in urine of non-exposed people was very low, but detectable. It is suggested that the method reported is suitable for the assessment of uptake of man to pyrene, a compound that is commonly present in work environments which are associated with pollution of polycyclic aromatic hydrocarbons.     

Biological exposure limit for occupational exposure to coal tar pitch volatiles at cokeovens

Summary Biological monitoring is an efficient tool in the evaluation of exposure to chemical agents. However, the dose-response of adverse health effects using biological exposure indices and biological limit values are rarely available. This paper presents an estimation of the occupational exposure limit value of 1-hydroxypyrene in urine, a biological exposure indicator of polycyclic aromatic hydrocarbons (PAH). A large-scale study of the exposure of cokeoven workers to PAH, in wich both air sampling (benzene soluble matter and individual PAH including benzo()pyrene) and biological monitoring (1-hydroxypyrene in urine) were applied, made it possible to establish an empirical mathematical relationship between the air sampling data and biological monitoring data. It was calculated that cokeoven workers with a urinary concentration of 1-hydroxypyrene of 2.3 mol/mol creatinine after a 3-day working period equals the airborne threshold limit value (TLV) of coal tar pitch volatiles (CTPV). Epidemiological studies have quantified the relative risk of lung cancer for topside and non-topside cokeoven workers. The published environmental exposure data of topside and non-topside cokeoven workers were used to determine the time-average exposure. The data of 1-hydroxypyrene in the urine of cokeoven workers and data of epidemiological studies from different coke plants were combined according to the concentrations of PAH in the air. Thus, it was possible to establish an indirect relationship between lung cancer mortality risk and the biological exposure indicator for cokeoven workers. Exposure at the level of the suggested tentative biological exposure limit (BEL) of 2.3 mol/ mol creatinine is estimated to be equal to a relative risk of lung cancer of approximately 1.3.     

Urinary 1-hydroxypyrene and 2-naphthol concentrations in male Koreans

Objective: Urinary 1-hydroxypyrene (1-OHP) has been used as a biological marker of exposure to polycyclic aromatic hydrocarbons (PAHs), and urinary 2-naphthol is suggested as a new marker for route-specific exposure to airborne PAHs. We analyzed urinary 1-OHP and 2-naphthol concentrations in 292 male Koreans (129 university students and 163 shipyard workers) to define the distribution pattern in Koreans with no or low occupational exposure to PAHs. Method: Histories of cigarette smoking and the eating of PAH-containing foods were obtained by a self-administered structured questionnaire. Urine samples were collected and urinary 1-OHP and 2-naphthol concentrations were measured using high-performance liquid chromatography (HPLC). Results: The arithmetic (geometric) means of urinary 1-OHP and 2-naphthol concentrations for all students, expressed as micromoles per mole of creatinine, were 0.04 (0.04) and 3.12 (2.22), for non-smokers 0.03 (0.03) and 1.78 (1.30) and for smokers 0.05 (0.03) and 4.36 (3.62), respectively. Among shipyard workers, the arithmetic (geometric) means of urinary 1-OHP and 2-naphthol concentrations were 0.69 (0.31) and 4.37 (2.62) for all, 0.27 (0.18) and 2.46 (1.16) for non-smokers, and 0.97 (0.44) and 5.60 (4.44) for smokers, respectively. Mean urinary 1-OHP and 2-naphthol concentrations differed significantly between non-smokers and smokers both in students and in shipyard workers. In smokers, some variables related to smoking habit were positively correlated with urinary 1-OHP and with 2-naphthol concentrations. The latter showed better correlations with the variables related to smoking amount than the former. None of the food-related factors was significantly correlated with urinary 1-OHP or 2-naphthol concentration. Conclusion: These results suggest that urinary 2-naphthol concentration is more sensitively affected by smoking status than urinary 1-OHP concentration and that urinary 2-naphthol is a sensitive marker for low-level inhalation of PAHs. Received: 6 March 2000 / Accepted: 26 July 2000     

Elimination of 1-hydroxypyrene after human volunteer exposure to polycyclic aromatic hydrocarbons

The aim of this study was to estimate the kinetics of 1-hydroxypyrene (1-HP) elimination after inhalation exposure to polycyclic aromatic hydrocarbons (PAHs). Samples of inhaled and exhaled air were collected on glass fiber filters backed with tubes filled with Amberlit XAD-2 resin. The filters were extracted by cyclohexane and Amberlit – by acetonitrile. Extracts for the determination of pyrene and benzo[a]pyrene (B[a]P) concentrations were analyzed by high-performance liquid chromatography (HPLC). 1-Hydroxypyrene in urine was determined after its preconcentration on a C-18 column (solid phase extraction method) using the same analytical technique. Five male volunteers were exposed for 6 h (two times, with a 1-month interval) to a PAH mixture at an aluminium plant. The volunteers were breathing at rest through facial mask equipped with a 1000-ml compensation container which allows collection of the exhaled air. Inhaled air samples were collected in the breathing zone of each volunteer. Urine samples were collected until the 71st hour after the onset of exposure. The average respiratory retention of pyrene was found to be 61%. The 1-HP elimination process could be described by one-compartment model with the half-live of 9.8 hour (95% CI 7.9–11.7 h). The simulation of 1-HP elimination in urine during a working week (4 days) indicates that the balance between absorption and elimination is achieved at the end of the second day. Received: 29 July 1996 / Accepted: 21 February 1997     

Inhalation and dietary exposure to polycyclic aromatic hydrocarbons and urinary 1-hydroxypyrene in non-smoking university students

Objective To examine which exposure pathway, dietary or inhalation, contribute more to the exposure to, and/or internal dose of, polycyclic aromatic hydrocarbons (PAHs) of non-smoking Japanese. Methods Duplicated diet, personal air samples and 24-h urine were collected from14 non-smoking male university students without occupational exposure and the concentrations of PAHs in diet and air and that of 1-hydroxypyrene (1-OHP) in urine were measured with HPLC-fluorescence detector. Results Daily dietary exposure contributed more than 90% of the total (diet + inhalation) daily exposure level for pyrene (diet/inhalation: 757/1.2 ng/day), benzo[k]fluoranthene (25/1.7 ng/day) and benzo[a]pyrene (91/2.1 ng/day). Urinary excretion of 1-OHP (median: 37 ng/day) was statistically significantly correlated only with dietary PAHs exposure level but not with inhalation. Conclusion Countermeasures to lower PAHs levels in atmosphere has been successful in Japan and more attention should be directed to dietary exposure to PAHs for reducing cancer risk in general population.     

Environmental exposure of small children to polycyclic aromatic hydrocarbons

Objectives: The aim of the study was to assess the intake (by various routes of exposure) of polycyclic aromatic hydrocarbons (PAH) by children living in a Czech city, and its effect on excretion of 1-hydroxypyrene (1-OHP) in summer and winter periods. Methods: Four groups of children (3–6 years old) were chosen: (1) two groups from a kindergarten situated in the city center with a higher traffic density (“polluted” area); (2) two groups from a kindergarten situated in a green zone of the same city (“non-polluted” area). Food consumption was recorded in all children and PAH intake from foodstuffs was estimated. Ambient air samples were collected from the playground and inside the kindergartens. Soil samples were collected too. Morning and evening urine samples were collected during sampling days. Results: In both seasons, the mean outdoor total PAH concentration (sum of 12 individual PAH) in the “polluted” area was approximately three-times higher than that in the “non-polluted” area. Indoor concentration in the “polluted” area was more than six-times higher than that in the “non-polluted” area in summer, and almost three-times higher in winter. The same trend was observed for pyrene and for the sum of carcinogenic PAH. The contribution to the total pyrene absorbed dose from food consumption was much more important than that from inhalation and from ingestion of soil dust. Significantly higher urinary concentrations of 1-OHP (evening samples) were found in children from the “polluted” kindergarten in both seasons. The number of significant relationships between 1-OHP and pyrene absorbed dose was weak. Conclusions: Food seems to be the main source of total pyrene and total PAH intake in small children, even under relatively higher air PAH exposure in the city. Estimated pyrene ingestion from soil had a negligible contribution to the total pyrene absorbed dose. Urinary 1-OHP seems to be an uncertain (non-sensitive) marker of the environmental inhalation exposure to pyrene (PAH) if the pollution of air by pyrene (PAH) is not excessive and the pyrene (PAH) dose by this route is much less than by ingestion. Usefulness of the urinary 1-OHP as an indicator of overall environmental exposure to PAH needs further investigation. Received: 18 September 2000 / Accepted: 20 February 2001     

Comparison of 1-hydroxypyrene exposure in the US population with that in occupational exposure studies

Urine samples collected in 1999 and 2000 as part of the National Health and Nutrition Examination Survey (NHANES) were analyzed for 14 monohydroxy polycyclic aromatic hydrocarbons (PAHs), and, for the first time, reference range values were calculated for these metabolites in the US population. Pyrene is a major component of most PAH mixtures and often is used as a surrogate for total PAH exposure. We detected 1-hydroxypyrene (1-OHpyrene), a metabolite of pyrene, in more than 99% of the samples. The overall geometric mean concentration for 1-OHpyrene in the USA was 79.8 ng/l, with a 95% confidence interval (CI) of 69.0–92.2 ng/l. The overall geometric mean creatinine-adjusted urinary 1-OHpyrene levels in the USA was 74.2 ng/g creatinine (0.039 mol/mol), with a 95% CI of 64.1–85.9 ng/g creatinine (0.034–0.046 mol/mol). There were no statistically significant differences among age, gender, or race/ethnicity groups. Adult smokers in the USA have urinary 1-OHpyrene levels three times higher than those of non-smokers. This difference was statistically significant. In this paper, we compare the reference range of urinary 1-OHpyrene levels with levels reported from various occupations by other researchers.     

1-Hydroxypyrene as a biomarker of PAH exposure among subjects living in two separate regions from a steel mill

Objective Steel mills are known to be a source of ambient polycyclic aromatic hydrocarbons (PAHs), and increased cancer risk has been reported among neighborhoods previously. In this study, we tried to assess the exposure to PAHs among residents nearby to a large steel mill in Korea by measuring urinary 1-hydroxypyrene (1-OHP). Methods Two separate areas at different distances from a steel mill but on the same wind direction were chosen to evaluate the environmental exposures to polycyclic aromatic hydrocarbons. Three-hundred and fifty children living in the vicinity of steel plant (“nearby” group) and 606 children residing much farther from the factory (“remote” group) participated. Urine was collected on three consecutive days, and questionnaires about exposure to passive smoking and food consumption as well as demographics were obtained. Routine monitoring data of ambient pollutants were obtained and particulate matter less than 10 μm (PM₁₀) was analyzed with multiple regressions to assess the associations with urinary 1-OHP. Results The geometric mean concentration of urinary 1-OHP among nearby group (0.048 ± 1.878 μmol/mol creatinine, GM ± GSD) was approximately 1.3 times higher than that among remote group (0.036 ± 2.425 μmol/mol creatinine, GM ± GSD), and using multiple regression techniques, the difference was significant (P < 0.0001) after adjusting for confounding variables. When different periods before the sampling of urine were examined, PM₁₀ averages over 2 days, 3 days, and 1 week prior to urine sampling showed significant associations with urinary 1-OHP levels. Conclusion Our findings are consistent with the interpretation that residents nearby to a steel mill are exposed to PAHs through ambient exposures.     

Smoking and dietary intake of polycyclic aromatic hydrocarbons as sources of interindividual variability in the baseline excretion of 1-hydroxypyrene in urine

Summary Seventy-six male volunteers, who were not occupationally exposed to polycyclic aromatic hydrocarbons (PAHs), participated in a study on the effect of tobacco smoking, alcohol consumption, dietary PAH intake, age, and body fat content on the baseline excretion of 1-hydroxypyrene in urine. Major determinants of urinary 1-hydroxypyrene excretion were smoking, dietary PAH intake, and age. The mean 1-hydroxypyrene concentrations in the urine of the volunteers in this study ranged between 0.05 and 0.79 mol/mol creatinine. Smokers excreted on average 0.25 mol/mol creatinine (range: 0.10–0.79 mol/mol creatinine), and nonsmokers on average 0.12 mol/mol creatinine (range: 0.04–0.29 mol/mol creatinine). The average number of cigarettes smoked per day correlated well with urinary 1-hydroxypyrene concentrations (r _s = 0.67, P < 0.001). The consumption of PAH-containing food products and active smoking account for 99% of total pyrene intake. The effect of age on 1-hydroxypyrene excretion is probably caused by a lower creatinine excretion in the elderly. Passive smoking and fat content had a statistically significant, but negligible effect on urinary 1-hydroxypyrene excretion. Passive smoking and the inhalation of ambient air are relatively inimportant for total pyrene intake (both account for less than 1%). Neither the consumption of alcohol nor the inhalation of ambient air significantly affected urinary 1-hydroxypyrene excretion. It is concluded that when urinary 1-OH-pyrene excretion is used in the assessment of PAH exposure, one should particularly be aware of the interindividual variability of the baseline excretion of PAH metabolites due to tobacco smoking and dietary PAH intake.     

核仁区嗜银蛋白作为多环芳烃暴露效应标志的研究

目的研究焦炉工人外周血T淋巴细胞核仁区嗜银蛋白(AgNOR)是否可作为多环芳烃暴露的效应标志。方法选取52名焦化厂职工(按焦炉逸散物暴露水平分为高、中、低暴露组)和10名非职业多环芳烃暴露人员(对照组)作为研究对象。采集外周血,经培养、制片、银染,用核仁银染面积/细胞核面积(I/S)衡量T淋巴细胞AgNOR相对含量;同时检测尿1羟基芘的水平,作为接触多环芳烃的内暴露标志。结果高、中、低暴露组和对照组工人尿1羟基芘的平均浓度分别为(16.56±2.77)、(7.17±3.05)、(3.30±2.77)和(3.04±1.58)μmol/mol肌酐,高暴露组与低暴露组和对照组比较,差异有统计学意义;高、中、低暴露组和对照组工人T淋巴细胞AgNOR的I/S值分别为0.056±0.010、0.065±0.013、0.067±0.008和0.076±0.007,高暴露组与其他3组比较以及中、低暴露组与对照组比较,差异均有统计学意义。结论职业多环芳烃暴露可导致尿1羟基芘水平上升和外周血T淋巴细胞AgNOR相对含量下降,提示多环芳烃暴露可损伤T细胞免疫功能,AgNOR有可能作为多环芳烃暴露的效应标志。     

萘代谢产物-白蛋白加合物作为焦炉工接触生物标志物的初步探索

目的探讨萘代谢产物的白蛋白加合物作为焦炉工接触生物标志物的可行性。方法随机选取某焦化厂28名焦炉作业工人(接触组)和22名对照个体(对照组),工人在连续工作4d的班后采集静脉血和尿样,并使用调查表收集个人信息。采用气相色谱质谱联机方法测定血浆中白蛋白加合物。结果在接触组及对照组中均检测出1,2萘醌及1,4萘醌与白蛋白的加合物(1,2NPQAlb和1,4NPQAlb)。接触组1,2NPQAlb水平(766pmol/g)高于对照组(449pmol/g),差异有统计学意义;1,4NPQAlb水平在接触组(486pmol/g)和对照组(442pmol/g)间差异无统计学意义。接触组1,2NPQAlb水平(766pmol/g)高于1,4NPQAlb(486pmol/g),差异有显著性。尿中萘、1萘酚、2萘酚及1羟基芘浓度与1,2NPQAlb水平间呈显著相关性,而与1,4NPQAlb之间未见明显的相关关系。结论1,2NPQAlb可有效地反映个体中长期暴露于气态多环芳烃的内剂量水平,有可能作为生物标志物用于焦炉工的生物监测。     

尿中1-羟基芘作为焦炉工多环芳烃暴露生物监测指标的研究

目的探讨焦炉工外暴露等级与尿中1-羟基芘(1-OHPy)浓度的关系。方法以某焦化厂120名生产工人和30名非接触者为研究对象,收集班后6h尿,并收集个人信息,用高效液相法测定尿中1-羟基芘。结果尿中1-羟基芘浓度呈炉顶>炉侧>炉底>对照组的趋势。与外暴露呈显著相关性(r=0.653,P<0.01),同样外暴露条件下,吸烟者尿中1-羟基芘显著高于未吸烟者(P<0.05)。结论焦炉工尿中1-羟基芘水平与外暴露等级存在明显的相关性,可反映多环芳烃暴露个体的内剂量水平。     

Creatinine normalization in biological monitoring revisited: the case of 1-hydroxypyrene

Objectives To compare the apparent urinary excretion rates of both creatinine and 1-hydroxypyrene (1-OHP) and to assess the value of creatinine normalization for both toxicokinetic analysis and the routine examination of workers.Methods All urine samples were collected from individuals who had been exposed to polycyclic aromatic hydrocarbons (PAHs), occupationally and non-occupationally, for at least 24 consecutive hours. Urinary creatinine and 1-OHP were determined. 1-OHP excretion rates were expressed either as a function of creatinine excretion rate or as unadjusted values. Theoretical relationships between creatinine-normalized excretion of metabolites and body weight-adjusted inhaled dose were drawn for men with a constant body mass index.Results Creatinine excretion rate paralleled 1-OHP excretion rate. The plot of creatinine excretion rate–adjusted excretion rate of 1-OHP vs time led to smooth curves for determination of toxicokinetic parameters. Creatinine normalization was adequate, even for samples with a urinary creatinine concentration below 0.5 g/l or above 3 g/l. A theoretical analysis revealed that men weighing between 50 kg and 100 kg, exposed to a constant dose of a pollutant producing a urinary metabolite excreted by the same mechanism as creatinine, would exhibit a body weight-adjusted dose span of 2 with an accompanying creatinine-normalized metabolite excretion span of 2.23-fold.Conclusion The kinetics of creatinine excretion parallels that of 1-OHP, and a creatinine excretion rate–normalized excretion rate of 1-OHP appears to allow for a better determination of the toxicokinetic parameters of 1-OHP urinary excretion. At least in the case of 1-OHP, creatinine normalization seems valid, even for very dilute or very concentrated urine samples. Finally, because creatinine normalization not only compensates for variable diuresis but also correlates better with the body weight-adjusted dose of the parent compound, it should be used in biological monitoring of exposure to (PAHs) pyrene and to other substances whose urinary biomarker excretion kinetics parallel that of creatinine.     

Biological monitoring of occupational exposure to polycyclic aromatic hydrocarbons (PAH) by determination of monohydroxylated metabolites of phenanthrene and pyrene in urine

Objectives The aim of our study was to assess individual polycyclic aromatic hydrocarbon (PAH) exposure of workers coming from three different industrial branches by several parameters of external and internal exposure. By analysing the relationships between those markers the suitability of individual parameters [e.g. monohydroxylated phenanthrene (Phe) metabolites] for exposure surveillance should be evaluated. Methods The total study population consisted of 255 male workers (age: 19-62, mean: 39.61 years), who were employed in coke production (n = 40), production of graphite electrodes and special carbon products (92), or production of refractory materials (123), respectively. For each worker external PAH exposure was determined by personal air sampling of 16 PAH, including Phe, pyrene (Pyr) and benzo[a]pyrene (BaP). For determination of internal PAH exposure the excretion of the PAH metabolites 1-, 2 + 9-, 3-, 4-hydroxyphenanthrene and 1-hydroxypyrene was measured in post-shift urine samples of all workers. Results In the total study population median total PAH exposure and exposure to BaP were 30.62 and 0.27 μg/m3, respectively. A calculation of PAH profiles resulted in substantial branch-related variations with Phe being a major component. Considering all branches the median excretions of 1-hydroxypyrene and hydroxyphenanthrenes (sum) were 6.68 and 11.22 μg/g creatinine. A correlation analysis yielded a good correlation between total ambient PAH exposure and excretion of hydroxyphenanthrenes in urine (r = 0.662; P < 0.01), but no significant correlation between Phe metabolites and the carcinogenic BaP. For 1-hydroxypyrene and BaP a weak but significant association was found (r = 0.235; P < 0.01). Conclusions Considering the results of the correlation analysis hydroxyphenanthrenes in urine should reflect an uptake of lowly condensed volatile PAH rather than an incorporation of highly condensed PAH like BaP which should be reflected better by 1-hydroxypyrene. Therefore, the determination of hydroxyphenanthrenes in addition to the well-established marker 1-hydroxypyrene could offer some further information about the exposure situation at a particular work place.     

孕期多环芳烃暴露对早产影响的研究进展

多环芳烃（PAH）是广泛存在于环境中的有毒污染物,可以通过呼吸道、消化道等多种方式进入人体。孕妇和新生儿是重要的敏感人群,相关的研究证据表明孕期PAH暴露可能是早产发生的重要原因,但具体的作用机制不是十分明确,可能与DNA损伤、氧化应激、全身炎症反应、内分泌干扰等有关。本文就孕期PAH暴露的影响因素和评价方法、孕期PAH暴露可增加早产的发生风险和可能的作用机制进行了综述。     

代谢酶基因多态性对孕期妇女尿中1-羟基芘水平的影响

目的 探讨代谢酶基因多态性对孕期妇女尿1-羟基芘(1-OHPy)水平的影响.方法 于2006年10月-2008年1月,在太原市两所二级甲等综合性医院中随机调查符合条件的孕期妇女347名,进行流行病学调查和生物样品的收集.采用高效液相色谱法测定尿样中1-羟基芘水平,应用多重PCR和限制性内切酶PCR(RFLP-PCR)技术分析四种代谢酶基因多态性(GSTM1,GSTT1,GSTP1,CYP1A1 Msp I).结果 校正年龄、教育水平等因素后,携带CYP1A1纯合突变基因型的孕期妇女其尿样1-OHPy水平(1.653 0 μmol/mol Cr)明显高于野生型(1.162 4 μmol/mol Cr),差异有统计学意义(P=0.047);携带GSTP1纯合突变基因型的孕期妇女尿样1-OHPy水平(1.1721μmol/mol Cr)明显高于野生型(0.8679μmol/mol Cr).差异有统计学意义(P=0.009);多基因模型中,CYP1A1和GSTP1对孕期妇女尿样1-OHPy浓度具有修饰作用(P=0.046,P=0.029),多基因模型的决定系数为0.262;基因-基因交互作用分析显示对尿中1-OHPy浓度有修饰作用的多态位点主要有CYP1A1和GSTM1.结论 代谢酶基因多态性在PAHs体内代谢中具有修饰作用,CYP1A1、GSTP1基因多态性对于孕期妇女体内芘代谢中可能起着重要作用,CYP1A1与GSTM1对芘的代谢具有交互作用.     

Urinary carcinogenic 4–6 ring polycyclic aromatic hydrocarbons in coke oven workers and in subjects belonging to the general population: Role of occupational and environmental exposure

AimA new solid phase microextraction–gas chromatography–mass spectrometry method (SPME–GC–MS) to detect urinary unmetabolized 3-, 6-ring polycyclic aromatic hydrocarbons (PAHs) was applied to coke oven workers and general population subjects with the aim to assess exposure to carcinogenic PAHs, to evaluate the role of occupational and environmental variables on PAHs levels, and to compare present results with those previously obtained with a less sensitive method.MethodsA total of 104 coke oven workers (CW) from Poland [recruited in 2000 (CW-2000; n = 55) and 2006 (CW-2006; n = 49)], and 45 control subjects from the same area, provided urine spot samples for measurement of 10 PAHs (from phenanthrene to benzo[g,h,i]perylene). The comparison between the two methods was performed only on CW-2000 subjects. Information regarding personal characteristics and job variables was collected by a questionnaire.ResultsThe new method enables the quantification of 5-, 6-ring PAHs; precision and accuracy were in the 7.3–20.8% and 89.4–110% range, respectively; in CW-2000 samples results obtained with the new and the old method were highly correlated (Lin's concordance correlation coefficients: from 0.790 to 0.965); the mean difference between measured PAHS increased with the molecular weight of the analytes (from +5 to +27%). Urinary PAHs were above or equal to the quantification limit, depending on the compound, in 67–100% (min–max), 26–100% and 6–100% of samples from CW-2000, CW-2006 and controls, respectively. Chrysene and benz[a]anthracene were the most abundant carcinogenic PAHs with median levels of 43.4, 13.4, and 2.3 ng/L and 45.9, 14.9, and 0.7 ng/L in CW-2000, CW-2006, and controls, respectively, while benzo[a]pyrene levels were 6.5, 0.7 and <0.5 ng/L. The multiple linear regression model showed that the determinants of exposure were the use of wood and/or coke for house heating for controls, and job title or the plant for CW-2006.ConclusionsUrinary benzo[a]pyrene and other carcinogenic PAHs were, for the first time, quantified in urine samples from both occupationally and environmentally exposed subjects. These results show that urinary PAHs can discriminate exposure at different levels. Moreover, the simultaneous determination of several PAHs allows for the development of excretion profiles to assess exposure to specific compounds.     

石化企业周边中老年居民的多环芳烃内暴露水平研究

目的了解我国石化企业周边居民体内多种多环芳烃（PAHs）的内暴露水平与分布特征。方法于2012年7月选取我国南方某大型石化企业,采用系统抽样法在石化企业周边收集到当地≥45岁居民的尿样。采用快速液相色谱-三重四级杆串联质谱仪检测多环芳烃羟基代谢物（OH—PAHs）。结果本研究共调查165名≥45岁石化企业周边居民,男、女性分别为81、84人,以45～64岁居民为主,占62．82％（102／165）。职业构成主要以农民为主,占49．09％（81／165）。检出2-羟基萘（2-OHN）、1-羟基萘（1-OHN）、2-羟基芴＋3-羟基芴（2-＋3-OHF）、2-羟基菲（2-OHPhe）、3-羟基菲（3-OHPhe）、4-羟基菲（4-OHPhe）、1-羟基菲＋9-羟基菲（1-＋9-OHPhe）和1-羟基芘（1-OHP）10种OH-PAHs,其浓度的中位数分别为：1．83、1．34、0．51、0．14、0．21、0．07、0．69、0．25μmol／mol肌酐,除2-OHN和1-＋9-OHPhe之间无相关性,其他各OH-PAHs间均呈正相关关系（P〈0．05或P〈0．01）,相关系数在0．20～0．76之间。除OHPhes外,吸烟人群体内的其他OH-PAHs含量均高于不吸烟人群（P〈0．05或P〈0．01）。结论石化厂区域中老年居民尿液样本中以总羟基萘（1-OHN和2-OHN）为主,这与石化厂多环芳烃的污染主要是低环的化合物为主一致。