苯接触与尿中反-反式黏糠酸和苯巯基尿酸关系研究

目的探讨职业苯接触与尿中反-反式黏糠酸(ttMA)和苯巯基尿酸(SPMA)的相关性,评定两接触标志物作为生物监测指标的适用性。方法对44名制鞋厂接苯工人进行个体苯暴露水平的作业环境监测,采集当日班前与班后尿样,分别用高效液相色谱和液质联谱测定尿中ttMA和SPMA含量。结果个体苯接触浓度为2.57~146.11 mg/m3,几何平均浓度为(27.91±3.29)mg/m3。班后尿中ttMA和SPMA含量均较班前增高,差异有统计学意义(P0.01),班后ttMA和SPMA与空气苯浓度的相关系数分别为0.905(P0.01)和0.537(P0.01),个体苯接触代谢转化为ttMA和SPMA的相对内暴露指数(RIE)随苯接触浓度的增高而下降。结论在中、高浓度的苯接触时,班后尿ttMA与空气苯浓度的相关性优于SPMA。     

职业接触二甲基乙酰胺工人尿中甲基乙酰胺生物限值研究

目的 研制我国职业接触二甲基乙酰胺(DMAC)工人尿中甲基乙酰胺(NMAC)的生物限值.方法 选择3家氨纶生产企业201名接触DMAC工人,应用个体采样器采集工作周末工作日的车间空气样品,用气相色谱法检测个体DMAC接触水平,同时收集当日工人班末尿样,应用气相色谱法测定尿中NMAC浓度以评价DMAC接触工人内暴露水平.通过内外剂量的回归方程、百分位数和相对内暴露(RIE)指数计算,推荐我国职业接触二甲基乙酰胺工人尿中NMAC生物接触限值.结果 201名DMAC接触工人中接触浓度符合我国DMAC接触限值133名,占66.2％,接触浓度范围在0.40～300.12mg/m3,几何平均浓度为19.4 mg/m3.工作周末班未尿中NMAC浓度范围为1.30～189.42 mg/g Cr,几何平均浓度为23.7 mg/g Cr.尿中NMAC浓度与个体DMAC外暴露浓度有相关性(F=188.872,R2=0.487,P＜0.001),回归方程为log(NMAC mg/g Cr)=0.685+0.455 log(DMAC mg/m3).以我国DMAC职业接触限值PC-TWA为20 mg/m3推算,尿中NMAC浓度为18.92 mg/g Cr.当工作场所空气中DMAC＜20 mg/m3时,90％的工人尿中NMAC水平为23.9 mg/g Cr.按RIE指数推算的尿中NMAC为19.0 mg/g Cr.结论 参考国外DMAC生物接触限值标准,建议我国DMAC生物接触限值为工作周末班未尿中NMAC 20 mg/g Cr.     

低浓度苯接触工人尿中代谢产物与苯暴露浓度相关性分析

目的 分析低浓度苯接触工人尿中代谢产物苯巯基尿酸（s-phenylmercapturic acid,SPMA）和反-反式黏糠酸（trans,trans-muconic acid,t,t-MA）与苯暴露浓度的相关性。方法 2018年9月—2021年9月选择山东省某鞋厂和篮球厂共117名苯接触工人作为接苯组,80名鞋厂和食品厂不接触苯的工人为对照组。通过被动个体采样方式进行工人苯暴露浓度监测,收集工人班后尿并检测尿中SPMA和t,t-MA浓度。分析内、外暴露指标的相关性及相对内暴露指数（relative internal exposure index,RIE index）随空气苯暴露浓度的变化趋势。结果 苯接触组工人空气苯浓度在1.00～107.40 mg/m3之间,M(P25,P75)为4.14(2.71,6.63)mg/m3,71%的苯接触组工人空气苯浓度低于我国工作场所空气中苯时间加权平均容许浓度限值（6.00 mg/m3）,对照组工人空气苯浓度低于检出限值。苯接触组工人尿中代谢产物SPMA浓度、t,t-MA浓度与对照组尿中相应苯代谢产物浓度的差异均有统计学意义（均P<0.05...     

职业接触可溶性铬盐个体暴露与尿铬水平的相关性研究

目的通过对职业接触可溶性铬盐个体暴露与尿铬水平的相关性研究,探讨并提出可溶性铬盐职业接触者尿铬生物限值,为铬盐职业接触人群健康监护和危险性评价提供依据。方法通过流行病学横断面调查,以不同剂量铬盐接触的83名劳动者为研究对象,10名非铬盐接触的农民为对照,两组人群在年龄、性别和吸烟状况等方面相匹配,进行了个体铬盐暴露与班末尿铬含量的研究,并对二者之间的关系进行了分析。同时复习了对可溶性铬盐职业接触者尿铬生物限值的相关文献。结果对照组8 h个体空气铬连续监测浓度在0.00~0.08μg/m3之间,尿铬浓度经肌酐校正后在0.40~1.02μg/g肌酐之间。铬盐接触劳动者8 h连续空气个体监测浓度在0.10~287.00μg/m3之间,尿铬浓度范围在1.14~79.07μg/g肌酐。职业接触铬盐工人班末的尿铬浓度随个体铬盐暴露水平的增加而增加,两者具有相关性。其回归方程为尿铬浓度(μg/g肌酐)=4.16+236.86×空气中铬的浓度(mg/m3),尿铬与空气铬的浓度相关系数r=0.976。通过文献复习,美国政府职业卫生工作者协会(ACG IH)推荐的职业接触可溶性铬盐在与我国相同的时间加权平均阈限值0.05mg/m3下,尿铬生物接触限值为65.1μmol/mol肌酐(30μg/g肌酐)。结论职业接触可溶性铬盐工人班末的尿铬含量可以用来评价作业场所铬盐的接触情况。依据美国ACG IH推荐的生物接触限值以及本调查结果,作者提出连续工作5个工作日的工作周末/班末尿铬的推荐值为65.1μmol/mol肌酐(30μg/g肌酐)。     

基于生物监测指标评估的低浓度苯暴露职业健康风险

目的通过流行病学调查资料和苯接触生物标志物的检测资料,初步建立基于生物监测指标的低浓度苯暴露致癌风险评价方法。方法根据苯的流行病学调查资料,基于多阶模型推导出低浓度苯职业暴露下的致癌风险模型。利用贝叶斯线性回归和马尔科夫链蒙特卡洛方法,采用R语言、JARG软件包和水晶球软件建立苯空气浓度与苯代谢物浓度函数关系并进行不确定性分析,并利用尿中苯巯基尿酸(S-phenylmercapturic acid,S-PMA)和反-反式黏糠酸(trans,trans-muconic acid,tt-MA)的浓度预测苯的致癌风险。结果考虑适用低浓度苯暴露的情况,建立了二项式的多阶模型用于表征致癌风险。基于建立的致癌风险模型,我国现行的职业接触限值[空气中苯的时间加权平均容许浓度6 mg/m^(3),工作班后尿S-PMA浓度100μg/g(以Cr校正),班后尿tt-MA浓度3.0 mg/g(以Cr校正)]下的致癌风险分别为5.64×10^(-4)、2.31×10^(-4)、1.52×10^(-4),均高于美国环境保护署(EPA)和疾病预防控制中心(CDC)提出的职业人群致癌风险可接受水平(10^(-4))。结论利用苯的代谢产物预测致癌风险,显示在空气中苯浓度低于职业接触限值的情况下,苯的致癌影响仍然存在。需要采取工程控制及个体防护等措施,尽可能降低苯的致癌风险。目前我国苯职业接触限值存在尽可能降低的必要性。     

职业接触二甲苯尿中甲基马尿酸生物限值的研究

选择不同暴露水平的二甲苯接触个体,检测个体二甲苯暴露浓度,同时采集当日工人班末尿样,对尿中二甲苯的代谢产物甲基马尿酸的含量进行测定,将二甲苯的外暴露空气浓度与体内甲基马尿酸代谢量进行回归分析,结合国外限值资料,提出适合我国职业卫生现状的甲基马尿酸生物限值的建议。接触工人在空气中二甲苯浓度为0～144.21 mg/m3时,班末尿中甲基马尿酸(MHA)与空气中二甲苯浓度之间存在良好相关性,肌酐校正回归方程为y(g/g肌酐)=0.0052x(mg/m3)+0.0112,r=0.731;比重校正回归方程为y(g/L)=0.0089x(mg/m3)-0.0259,r=0.793。将我国二甲苯职业接触限值50 mg/m3分别代入回归方程,推出工作班末尿中甲基马尿酸含量为0.271 g/g肌酐和0.419 g/L。依据我国二甲苯实际接触情况,参考国外相关标准和文献,建议我国职业接触二甲苯的代谢产物尿中甲基马尿酸的生物接触限值为班末尿0.3 g/g肌酐或0.4 g/L。     

锰职业接触工人生物标志物的研究

目的 探讨锰接触工人个体实际接触剂量与生物指标之间的关系,以寻找合适的早期生物学监测指标.方法 选择济南市某机车车辆厂电焊作业工人270名,收集其血液和尿液.原子吸收光谱法测定血锰、尿锰和个体锰接触剂量;高效液相色谱荧光法测定尿中高香草酸(HVA)和香草扁桃酸(VMA);对各指标进行相关性分析.结果 个体锰接触剂量(CTWA)为0.005 5～1.957 7mg/m3,平均浓度为(0.25±0.31)mg/m3;接锰工人尿锰浓度为0.011 2～2.447 2μg/mg Cr,平均(0.22±0.31)μg/mg Cr;血锰浓度为0.06～38.70 μg/ml,平均(3.94±6.66)μg/ml;尿HVA浓度为0.102～4.780 μg/mg Cr,平均(1.01±0.78)μg/mg Cr;VMA浓度为0.032～2.768 μg/mg Cr,平均(0.61±0.35)μg/mg Cr.个体锰接触剂量与血锰、尿锰、尿中VMA之间均无相关性(P＞0.05);个体锰接触剂量与尿中HVA呈负相关,差异有统计学意义(r=-0.168,P＜0.01).结论 血锰、尿锰、尿中VMA均不能作为评价锰接触的接触生物标志物;尿中HVA可以作为评价锰接触的效应生物标志物.     

职业性苯暴露反-反式粘糠酸生物接触限值研究

目的研究职业性苯暴露反．反式粘糠酸（t,t—MA）生物接触限值。方法实验室建立生产环境空气中苯浓度的气相色谱检测方法及作业工人尿中t,t—MA含量的高效液相色谱检测方法,并通过检测苯暴露现场工人8h苯暴露水平及班前、班后尿中t,t．MA含量,研究其相关性。结果苯暴露者班前、班后尿中t,t—MA含量与其苯暴露水平有明显的相关关系。班前y（mg／gCr）=0．924＋0．108X（me／m^3）,r=0．62,P〈0．01;班后y（mg／gCr）=2．103＋0．177X（mg／m^3）,r=0．791,P〈0．01。结论根据我国作业场所空气中苯的国家卫生标准,按回归方程推导出职业接触苯生物接触限值,推荐职业暴露苯的生物接触限值为工作班班后尿t,t．MA含量为3．0mg／gCr,下一班班前尿t,t．MA含量为1．5mg／gGr。     

职业接触汞生物限值的研制

对职业接触汞工人进行体检和尿汞检测,分析尿汞与工作场所空气中汞浓度及临床表现的关系,并参考国外职业接触汞的生物限值,提出我国职业接触汞的生物限值为尿总汞20μmol/mol Cr（35μg/g Cr）。     

甲苯二异氰酸酯职业接触人群尿中代谢产物调查

为探讨职业环境中甲苯二异氰酸酯(TDI)水平和接触人群尿中甲苯二胺(TDA)水平的关系,为建立TDI职业接触的生物限值提供依据,选取深圳市2家企业61名作业工人作为接触组,另选取同企业的50名行政、后勤人员(不接触TDI)为对照组,采用气相色谱法测定车间空气中TDI水平以及2组人群尿中TDA水平,并对其相关关系进行分析。结果显示,接触组工人接触TDI浓度中位数为0.051 mg/m3,尿中TDA浓度中位数为0.563μmol/mol Cr;对照组人群接触TDI水平低于检出限(0.000 2 mg/m3),尿中TDA水平低于检出限(0.025μmol/mol Cr)。接触组人群班末尿中TDA的水平与工作场所空气中TDI水平呈正相关性[r=0.675,P0.05],尿中TDA水平(y赞,μmol/mol Cr)对工作场所空气中TDI浓度(x,mg/m3)的回归方程为:y赞=8.065 x+0.147(r=0.675,P0.05),按照我国现行的工作场所空气中TDI时间加权平均容许浓度(PCTWA=0.1 mg/m3)推算,接触工人班末尿中TDA水平为0.954μmol/mol Cr。提示本研究的职业接触甲苯二异氰酸酯生物标志物监测方法适用于评价作业环境接触人群的职业接触水平。     

Validity of new biomarkers of internal dose for use in the biological monitoring of occupational and environmental exposure to low concentrations of benzene and toluene

Objectives

This study analyzes the validity of new, more sensitive and specific urinary biomarkers of internal dose, namely, urinary benzene for benzene and urinary toluene and S-benzylmercapturic acid (SBMA) for toluene, to assess their efficacy when compared to traditional biomarkers for biological monitoring of occupational exposure to low concentrations of these two toxic substances.

Methods

Assessment was made of 41 workers occupationally exposed to benzene and toluene, 18 fuel tanker drivers and 23 filling-station attendants, as well as 31 subjects with no occupational exposure to these toxic substances (controls). Exposure to airborne benzene and toluene was measured using passive Radiello^® personal samplers worn throughout the work shift. In urine samples collected from all subjects at the end of the workday, both the traditional and the new internal dose biomarkers of benzene and toluene were assessed, as well as creatinine so as to apply suitable adjustments.

Results

Occupational exposure to benzene and toluene resulted significantly higher in the fuel tanker drivers than the filling-station attendants, and higher in the latter than in controls. Significantly higher concentrations of t,t-muconic acid (t,t-MA), S-phenylmercapturic acid (SPMA), urinary benzene, SBMA and urinary toluene were found in the drivers than the filling-station attendants or the controls. Instead, urinary phenol and hippuric acid were not different in the three groups. In the entire sample, airborne benzene and toluene values were significantly correlated, as were the respective urinary biomarkers, showing coefficients ranging from 0.36 to 0.98. Subdividing the subjects by smoking habit, higher coefficients were evident in non-smokers than in smokers; at multiple regression analysis t,t-MA, SPMA and urinary benzene and toluene were dependent on the number of cigarettes smoked daily and on airborne benzene and toluene, respectively. Instead, SBMA was dependent only on airborne toluene.

Conclusions

Our research confirmed the validity of t,t-MA and SPMA for use in the biological monitoring of exposure to low concentrations of benzene. Urinary benzene showed comparable validity to SPMA; both parameters are affected by smoking cigarettes in the hours before urine collection, so it is best to ask subjects to refrain from smoking for 2 h before urine collection. Urinary toluene was found to be a more specific biomarker than SBMA.     

低苯暴露人群尿中t，t-MA及S-PMA的生物监测

目的分析职业低苯和环境低苯接触与人体尿液中t,t-MA和S-PMA浓度的相关性。方法选取广州市某制鞋厂钳帮和刷胶工人等苯职业接触人员作为职业低苯暴露人群（职业组）,选取非职业苯接触且家庭1年内装修过并已入住半年以上的人员作为环境低苯接触人群（环境组）。采用超高效液相串联质谱联用（UPLC—MS／MS）内标法测定尿中t,t-反式粘糠酸（t,t-MA）及苯巯基尿酸（S-PMA）含量,采用气相色谱法检测空气中苯浓度。结果职业组个体空气暴露的苯浓度（均值±标准差）为（0．16±0．06）mg／m^3,尿中t,t-MA及S-PMA含量分别为（42．7±39．2）和（0．28±0．19）μg／gCr;环境组个体空气暴露的苯浓度中位数（四分位间距）为0．01（0．02）mg／m^3,尿中t,t-MA及S-PMA含量的中位数（四分位间距）分别为20．5（16．2）和0．03（0．04）μg/gCr;经非参数Mann—WhitneyU—test检验分析发现：职业组的个体空气暴露苯浓度及尿中t,t-MA、S-PMA含量均高于环境组（均P〈0．01）。相关性分析结果显示,当空气中苯浓度为0．16mg／m^3时,尿中t,t—MA和S-PMA与空气中苯浓度存在良好的相关性（r=0．499、0．715）。结论t,t-MA及S-PMA可作为生物标记物用于职业低苯和环境低苯暴露的生物监测。     

Evaluation of urinary biomarkers of exposure to benzene: correlation with blood benzene and influence of confounding factors

Purpose   trans,trans-Muconic acid (t,t-MA) is generally considered as a useful biomarker of exposure to benzene. However, because of its lack of specificity, concerns about its value at low level of exposure have recently been raised. The aim of this study was (a) to compare t,t-MA, S-phenylmercapturic acid (SPMA) and benzene (B-U) as urinary biomarkers of exposure to low levels of benzene in petrochemical workers and, (b) to evaluate the influence of sorbic acid (SA) and genetic polymorphisms of biotransformation enzymes on the excretion of these biomarkers. Method  A total of 110 workers (including 24 smokers; 2–10 cigarettes/day) accepted to take part in the study. To assess external exposure to benzene, air samples were collected during the whole working period by a passive sampling device attached close to the breathing zone of 98 workers. Benzene was measured in blood (B-B) samples taken at the end of the shift, and was considered as the reference marker of internal dose. Urine was collected at the end of the shift for the determination of B-U, SPMA, t,t-MA, SA and creatinine (cr). B-U and B-B were determined by head-space/GC–MS, SPMA and SA by LC-MS, t,t-MA by HPLC-UV. Results  Most (89%) personal measurements of airborne benzene were below the limit of detection (0.1 ppm); B-B ranged from <0.10 to 13.58 μg/l (median 0.405 μg/l). The median (range) concentrations of the urinary biomarkers were as follows: B-U 0.27 μg/l (<0.10–5.35), t,t-MA 0.060 mg/l (<0.02–0.92), SPMA 1.40 μg/l (0.20–14.70). Urinary SA concentrations ranged between <3 and 2,211 μg/l (median 28.00). Benzene concentration in blood and in urine as well as SPMA, but not t,t-MA, were significantly higher in smokers than in non-smokers. The best correlation between B-B and urinary biomarkers of exposure were obtained with benzene in urine (μg/l r = 0.514, P < 0.001; μg/g cr r = 0.478, P < 0.001) and SPMA (μg/l r = 0.495, P < 0.001; μg/g cr r = 0.426, P < 0.001) followed by t,t-MA (mg/l r = 0.363, P < 0.001; mg/g cr r = 0.300, P = 0.002). SA and t,t-MA were highly correlated (r = 0.618, P < 0.001; corrected for cr r = 0.637). Multiple linear regression showed that the variation of t,t-MA was mostly explained by SA concentration in urine (30% of the explained variance) and by B-B (12%). Variations of SPMA and B-U were explained for 18 and 29%, respectively, by B-B. About 30% of the variance of B-U and SPMA were explained by B-B and smoking status. Genetic polymorphisms for biotransformation enzymes (CYP2E1, EPHX1, GSTM1, GSTT1, GSTP1) did not significantly influence the urinary concentration of any of the three urinary biomarkers at this low level of exposure. Conclusion  At low levels of benzene exposure (<0.1 ppm), (1) t,t-MA is definitely not a reliable biomarker of benzene exposure because of the clear influence of SA originating from food, (2) SPMA and B-U reflect the internal dose with almost similar accuracies, (3) genetically based inter-individual variability in urinary excretion of biomarkers seems negligible. It remains to assess which biomarker is the best predictor of health effects.     

Biological monitoring of workers exposed to carbon disulfide (CS2) in a viscose rayon fibers factory

The exposure-excretion relationship to carbon disulfide (CS₂) vapor in 407 exposed workers was studied during the second half of the working week. Carbon disulfide concentrations were also determined in 50 nonexposed subjects. The geometric mean value for CS₂ in urine samples from the latter was: 0.23 μg/l (95% upper limit = 0.52 μg/l) when log-normal distribution was assumed. Among the exposed workers, the CS₂ level in urine samples collected after the first half shift exceeded the 95% upper limit of nonexposed subjects in every case. The time-weighted average intensity of exposure to CS₂ vapor was measured using personal diffusive samplers (in which carbon cloth served as an adsorbent). CS₂ concentrations in urine were determined in samples collected at the end of the first half shift from the 407 exposed cases as well as from 50 nonexposed controls. There was a significant correlation (p < 0.0001) between the exposure to CS₂ vapor at concentrations of up to 64 mg/m³ and the levels of CS₂ measured in the urine samples after four hours of exposure. The correlation indicated that a mean level of 15.5 μg CS₂/l urine (95% confidence range, 13.8–17.1 μg/l) was excreted following an exposure to CS₂ at 31 mg/m³ (the current occupational exposure limit). Am. J. Ind. Med. 33:478–484, 1998. © 1998 Wiley-Liss, Inc.     

职业接触苯乙烯的生物限值研究

目的：研究职业接触苯乙烯的生物限值。方法：高效液相色谱法测定苯乙烯作业工人班前、班后尿中苯乙醛酸（PGA）和苯乙醇酸（MA）的含量，监测工人8h苯乙烯的接触水平，同时研究两者的相关性。结果：尿中的PGA和MA浓度与苯乙烯的接触量有明显的剂量－反应关系。根据作业场所空气中苯乙烯的国家卫生标准，按回归方程推导出职业接触苯乙烯的生物限值。结论：对职业接触苯乙烯的生物限值提出的推荐值：工作班末MA为220mmol/mol肌酐或300mg/g肌酐，下一班前为88mmol/mol肌酐或120mg/g肌酐；PGA班末为7mmol/mol肌酐或100mg/g肌酐，下一班前为30mmol/mol肌酐或40mg/g肌酐。     

Evaluation of occupational exposure to benzene by urinalysis

Urinary phenol determinations have traditionally been used to monitor high levels of occupational benzene exposure. However, urinary phenol cannot be used to monitor low-level exposures. New biological indexes for exposure to low levels of benzene are thus needed. The aim of this study was to investigate the relations between exposure to benzene (Abenzene, ppm), as measured by personal air sampling, and the excretion of benzene (U-benzene, ng/l),trans,trans-muconic acid (MA, mg/g creatinine), andS-phenylmercapturic acid (PMA, g/g creatinine) in urine. The subjects of the study were 145 workers exposed to benzene in a chemical plant. The geometric mean exposure level was 0.1 ppm (geometric standard deviation = 4.16). After logarithmic transformation of the data the following linear regressions were found: log (U-benzene, ng/l) = 0.681 log (A-benzene ppm) + 4.018; log (MA, mg/g creatinine) = 0.429 log (A-benzen ppm) – 0.304; and log (PMA, g/g creatinine) = 0.712 log (A-benzene ppm) + 1.664. The correlation coefficients were, respectively, 0.66, 0.58, and 0.74. On the basis of the equations it was possible to establish tentative biological limit values corresponding to the respective occupational exposure limit values. In conclusion, the concentrations of benzene, mercapturic acid, and muconic acid in urine proved to be good parameters for monitoring low benzene exposure at the workplace.