Biological monitoring of workers exposed to<Emphasis Type="Italic"> N</Emphasis>,<Emphasis Type="Italic">N</Emphasis>-dimethylformamide in synthetic leather manufacturing factories in Korea

Objectives To investigate the relationship between N,N-dimethylformamide (DMF) exposure and excretion of urinary N-acetyl-S-(N-methylcarbamoyl)cysteine (AMCC) and N-methylformamide (NMF) in workers at synthetic leather manufacturing factories in Korea, for the first time.Methods One-hundred forty-four male workers at nine synthetic leather manufacturing factories were surveyed. Exposure to DMF was evaluated through breathing zone air sampling followed by analysis via a gas chromatograph equipped with a flame ionization detector (GC-FID). The levels of NMF and AMCC were determined by a GC with a flame thermionic detector (GC-FTD). Urine samples were collected at the end of the workshift.Results and Conclusions Geometric mean of workplace air DMF and urinary NMF was 8.8 ppm and 47.5 mg/l, respectively, and the level of DMF and NMF was significantly correlated. The biological exposure limit for NMF (15 mg/ml) was exceeded in 89.5% of urine samples, and 37.9% of air samples exceeded the environmental DMF exposure limit (10 ppm), indicating a serious health risk to the employees of the synthetic leather industry in Korea. Exposure to 10 ppm DMF in the workplace air corresponded to a urinary NMF concentration of 53.4 mg/l. Alcohol intake the day before urine was sampled influenced NMF excretion into urine (40.5 mg/l NMF for the no-alcohol group and 94.6 mg/l for the group consuming more than 63.0 g alcohol/day). We could not find a significant relationship between air DMF and urinary AMCC concentration. Exposure to 10 ppm DMF corresponded to an AMCC concentration of 8.0 mg/l in the urine samples collected on the same day as the air was sampled.     

人造革厂工人二甲基甲酰胺经皮接触评估研究

目的 对人造革厂工人经皮肤接触二甲基甲酰胺(DMF)的水平进行评估。方法 采用洗手法和擦拭法对某人造革厂湿法配料、湿法涂台和三版印刷工人进行皮肤接触水平监测,同时对工人的吸入水平及尿中甲基甲酰胺(NMF)水平进行检测。结果 所有洗手液和擦拭液样品中均检测出DMF(洗手液：0.35～15.34 mg;擦拭液：29.58～110.45μg)。在洗手试验组中,洗手液中DMF总量与作业人员班末尿中NMF含量、累积接触水平与班末尿中NMF含量呈对数相关性;擦拭试验组中则各指标间无相关性。结论 洗手法是一种较好的研究DMF作业人员皮肤接触水平的方法,具有容易在现场实施以及结合生物监测结果等优点。     

二甲基甲酰胺生物接触限值的研究

目的研究我国职业接触二甲基甲酰胺(DMF)的生物限值。方法气相色谱法检测工作场所空气中二甲基甲酰胺浓度和作业工人班末尿中甲基甲酰胺(NMF)浓度,同时研究两者的相关性。结果 DMF接触者班末尿中NMF浓度与工作场所空气中DMF浓度有密切正相关(Y=0.3389X+3.0297,r=0.9986,P0.01)。根据作业场所空气中DMF的国家职业卫生标准,按回归方程推导出职业接触DMF的生物限值。结论 DMF接触者生物接触限值推荐值:班末尿中NMF为12.0 mg/gCr。     

Biological monitoring of workers exposed to N,N-dimethylformamide in the synthetic fibre industry

Objectives: Monitoring of workplace air and biological monitoring of 23 workers exposed to N,N-dimethylformamide (DMF) in the polyacrylic fibre industry was carried out on 4 consecutive days. The main focus of the investigation was to study the relationship between external and internal exposure, the suitability of the metabolites of DMF for biological monitoring and their toxicokinetic behaviour in humans.Methods: Air samples were collected using personal air samplers. The limit of detection (LOD) for DMF using an analytical method recommended by the Deutsche Forschungsgemeinschaft (DFG) was 0.1 ppm. The urinary metabolites, N-hydroxymethyl-N-methylformamide (HMMF), N-methylformamide (NMF), and N-acetyl-S-(N-methylcarbamoyl)-cysteine (AMCC), were determined in one analytical run by gas chromatography with thermionic sensitive detection (GC/TSD). The total sum of HMMF and NMF was determined in the form of NMF. The LOD was 1.0 mg/l for NMF and 0.5 mg/l for AMCC. Results and conclusions: The external exposure to DMF vapour varied greatly depending on the workplace (median 1.74 ppm, range <0.1–159.77 ppm). Urinary NMF concentrations were highest in post-shift samples. They also covered a wide range (<1.0–108.7 mg/l). This variation was probably the result of different concentrations of DMF in the air at different workplaces, dermal absorption and differences in the protective measures implemented by each individual (gloves, gas masks etc.). The urinary NMF concentrations had decreased almost to zero by the beginning of the next shift. The median half-time for NMF was determined to be 5.1 h. The concentrations of AMCC in urine were determined to be in the range from <0.5 to 204.9 mg/l. Unlike the concentrations of NMF, the AMCC concentrations did not decrease during the intervals between the shifts. For the exposure situation investigated in our study, a steady state was found between the external exposure to DMF and the levels of AMCC excreted in urine about 2  days after the beginning of exposure. AMCC is therefore excreted more slowly than NMF. The half-time for AMCC is more than 16 h. Linear regression analysis for external exposure and urinary excretion of metabolites was carried out for a sub-group of 12 workers. External exposure to 10 ppm DMF in air (the current German MAK value) corresponds to an average NMF concentration of about 27.9 mg/l in post-shift urine from the same day and an average AMCC concentration of 69.2 mg/l in pre-shift urine from the following day. NMF in urine samples therefore represents an index of daily exposure to DMF, while AMCC represents an index of the average exposure over the preceding working days. AMCC is considered to be better suited for biomonitoring purposes because (1) it has a longer half-time than NMF and (2) its formation in humans is more closely related to DMF toxicity. Received: 25 June 1999 / Accepted: 2 October 1999     

Exposure to solvents in a synthetic leather manufacturing plant

The objective of this study was to evaluate the exposure of synthetic leather workers to dimethylformamide (DMF), epichlorohydrin (ECH) and toluene, in a manufacturing plant. The correlation between biological and environmental monitoring for DMF was also investigated. Environmental monitoring of the three solvents included personal and area sampling based on time of day (morning and afternoon). Urine samples were taken at the end of the shift and urinary N-methylformamide (NMF) was then used to biologically monitor DMF levels. Results for solvent concentrations based on air sampling were considerably higher in area than in personal sampling. Of 41 area samples, 15 (36.6%) and five (12.2%) exceeded permissible exposure levels for DMF and ECH, respectively, compared with 22 (28.6%) and three (3.9%) based on 77 personal samples. Overall, urinary NMF concentrations were lower than the Biological Exposure Index (BEI) suggested by the American Conference of Governmental Industrial Hygienists (ACGIH). A significant correlation (r=0.32; P < 0.05) was found between environmental and biological monitoring. Even though urinary NMF concentration was within permissible levels for Taiwan, the authors recommend that immediate measures be taken to decrease DMF and ECH concentrations in synthetic leather manufacturing plants. Received: 14 June 1999 / Accepted: 20 November 1999     

N,N- Dimethylformamide – influence of working conditions and skin penetration on the internal exposure of workers in synthetic textile production

Objectives: This study examined the external and internal exposure to the solvent N,N-dimethylformamide (DMF) of 126 workers from a factory producing synthetic fibers. Methods: Air measurements were carried out using personal air samplers with diffusion tubes (Dräger, ORSA 5). For the purpose of biological monitoring the levels of N-methylformamide (NMF) in urine were measured in preshift and postshift samples. Determinations were carried out using gas chromatography. Anamnestic data were collected with standardized questionnaires, including personal data, working history and current working conditions, and former and current illness with regard to the effects of DMF. Skin diseases were documented by a dermatologist. Results: DMF concentrations measured in the air ranged between <0.1 and 37.9?ppm (median 1.2?ppm). Concentrations of NMF varied from 0.05 to 22.0?mg/l (preshift values) and from 0.9 to 100.0?mg/l (postshift values). The creatinine-related values (0.02–44.6?mg/g preshift; 0.4–62.3 postshift) were subject to less variation and therefore represented the level of exposure better than the values related to volume. Additional investigation of a subcollective (n?=?31) over a period of 4 days showed that NMF did not accumulate in the organism. The positive but relatively weak association observed between the DMF concentrations measured in the workplace air and the values recorded for internal exposure in this study can be explained by influencing factors such as dermal absorption or protective clothing. Interindividual differences in internal exposure were found for the specific work areas. The German BAT value (15?mg NMF/l urine) was exceeded in 36 persons (29%) despite the use of breathing protection and protective gloves, without increased values being measured in the air. Increased absorption without higher-level exposure could particularly also be observed in employees with eczema. Conclusions: From the point of view of the prevention of disease, biological monitoring is the best instrument for exposure assessment of workers exposed to DMF.     

Urinary determination of N-acetyl- S-( N-methylcarbamoyl)cysteine and N-methylformamide in workers exposed to N,N-dimethylformamide

OBJECTIVES: We conducted this biomonitoring study with the aim of evaluating the correlation between the excretion of N-methylformamide (NMF) (mainly from N-hydroxy- N-methylformamide) and N-acetyl- S-( N-methylcarbamoyl)cysteine (AMCC), and levels of exposure to N, N-dimethylformamide (DMF) among occupationally exposed subjects. METHODS: Exposure levels were determined by personal sampling: breathing zone air samples were collected by means of passive samplers. DMF collected by the charcoal in personal samplers was analysed after extraction with methanol by a gas chromatograph. For the purpose of biological monitoring the levels of NMF and AMCC were measured in pre-shift and post-shift samples. Determinations were carried out by, respectively, gas chromatography and high performance liquid chromatography (HPLC). RESULTS AND CONCLUSIONS: The mean time-weighted average (TWA) exposure was approximately half (13.5 mg/m(3)) of the current threshold limit value, the range of the values was from 0.4 to 75.2 mg/m(3). Environmental DMF concentrations exhibited a significant correlation with the specific mercapturic acid (AMCC) collected at the end of the working week (AMCC Friday morning mg/l=1.384xDMF (mg/m(3))+8.708; r(2)=0.47; P<0.008]; hence urinary AMCC represents an index of the average exposure during several preceding working days, making it possible to calculate the approximate relationship between DMF uptake and excretion of this metabolite. A significant correlation was found also between the daily excretion of NMF and the corresponding levels of DMF in air. The equation of the regression line was: NMF (mg/g creatinine)=0.936xDMF (mg/m(3))+7.306; r(2)=0.522 ( P<0.0001).     

Analysis of metabolites of <Emphasis Type="Italic">N,N</Emphasis>-dimethylformamide in urine samples

Aim To assess the suitability of different methods for biological monitoring of internal dose to N,N-dimethylformamide (DMF) in occupational settings.Methods The determination of urinary metabolites of DMF, N-hydroxymethyl-N-methylformamide (HMMF), N-methylformamide (NMF) and N-acetyl-S-(N-methylcarbamoyl) cysteine (AMCC) was carried out by four selected analytical procedures. Two methods solely measured total NMF (HMMF and NMF). The other two methods measured both total NMF and AMCC in one analytical run. All four methods were tested on 34 urine samples from workers exposed to DMF.Results Comparison of the four methods for determination of total NMF in urine showed that results were similar for three methods, while the remaining one provided NMF levels significantly lower (by 22%) than the other methods. Thus, all but one of the tested methods for the determination of total NMF can be considered to be suitable for biological monitoring of internal dose to DMF. The two tested methods for the determination of AMCC afforded results that showed high correlation but differed significantly (by 10%).Conclusion The choice of the biomonitoring method depends mainly on the purpose for which the measurement is conducted. For evaluation of acute exposures or to assess safety measures in the working area, an updated version of the traditional method of Kimmerle and Eben (1975a, b) for the determination of total NMF in urine is sufficient. For risk assessment after exposure to DMF, the determination of AMCC should be carried out, since AMCC, but not total NMF, is supposed to be related to the toxicity of DMF. However, there is still a need to develop an easier, more sensitive and more selective method for the determination of AMCC in urine until AMCC can be considered for regulatory purposes in occupational settings.     

二甲基甲酰胺作业工人皮肤污染量研究

目的 建立二甲基甲酰胺(DMF)接触工人皮肤污染量的测定方法,并对DMF接触工人皮肤污染情况进行研究.方法 选择不同岗位的37名DMF接触工人,随机分成异丙醇组(16人)和去离子水组(21人),分别以异丙醇和去离子水为擦拭溶剂,采用气相色谱法测定DMF的皮肤污染量,同时测定工人班末尿中甲基甲酰胺(NMF)含量,并对皮肤污染总量与尿中NMF进行相关分析.结果 异丙醇组均能检测出DMF含量,去离子水组均未检出DMF,样品图谱中其他杂峰与DMF峰能完全分离,无干扰.湿法岗位工人皮肤污染总量最高[(2.844±1.31)mg],后处理岗位[(2.50±0.95)mg]和干法岗位[(1.95±0.61)mg]次之,后处理三版印刷、干法配料和湿法配料岗位工人经呼吸道累积接触剂量分别为351.3、201.3、135.2 mg.3个岗位空气中DMF平均浓度为60.2、89.6、156.4 mg/m3,皮肤DMF污染总量与尿中NMF无明显相关,差异无统计学意义(r=0.176,P>0.05).结论 异丙醇是测定DMF皮肤污染较有效的擦拭溶剂;当工作场所空气中DMF浓度高于职业接触限值时,DMF以呼吸道吸收为丰要途径,但其皮肤吸收也不容忽视.     

Biological surveillance of workers exposed to dimethylformamide and the influence of skin protection on its percutaneous absorption

Summary Two studies were carried out among workers exposed to dimethylformamide (DMF) in an acrylic fiber factory. The first study involved 22 exposed workers and 28 control workers. Blood was examined at the beginning and at the end of a working week for the presence of biological signs of liver dysfunction. Pre- and post-shift urine samples were also collected during 1 week for determination of N-methylformamide (NMF) concentration. The airborne concentration of DMF was determined at different work places during the same period. On prevention of direct skin contact with DMF solution a significant correlation was found on a group basis between the concentration of DMF vapor and the NMF concentration in post-shift urine samples. When the concentration of NMF in post-shift urine samples from a group of workers does not exceed 30 mg/g creatinine, then their integrated exposure is probably below 60 mg/m³ × h (10 mg/m3 for 6 h). This exposure appears to be safe with regard to the risk of liver damage but does not necessarily preclude episodes of alcohol intolerance in some workers.During a second study, NMF concentrations in pre- and post-shift urine samples were followed-up in seven workers during three weeks when different personal protective devices were used. In an acrylic fiber factory, skin absorption was found to be more important than inhalation in the overall exposure to the solvent when no personal protective devices were used. The use of impermeable gloves with long sleeves appears to be the best method of preventing skin absorption of DMF. Silicone or glycerol barrier creams are less effective and should not be recommended.Part of this work was presented at the First International Congress on Toxicology in Toronto 1977     

二甲基甲酰胺对作业工人肾损害和心血管系统的影响

目的探讨二甲基甲酰胺（DMF）对作业工人肾损害和心血管系统的影响。方法选择2010年某合成革企业直接接触DMF工人139人作为接触组,根据DMF接触浓度和工龄把接触组分为高、中、低浓度接触组和工龄〈5年、工龄≥5年接触组。另选98名不接触DMF和其他有害因素的食品加工企业人员作为对照组,对2组进行肾功能、尿中β2-微球蛋白（β2-MG）、甲基甲酰胺（NMF）及心电图等检查,并对DMF作业环境进行职业卫生调查。结果共采集6个作业点DMF空气样品150份,浓度范围为2.6～282.6 mg/m3。其中超标作业点4个,超标率66.7%;有随接触DMF浓度增高肾功能指标（BUN）浓度增高的趋势,但各组别之间差异均无统计学意义（P〉0.05）;尿β2-MG检出值高浓度组高于其他各组,差异有统计学意义（P〈0.05）,中、低浓度组与对照组比较,差异无统计学意义（P〉0.05）;DMF接触者班末尿中NMF浓度与作业场所DMF暴露水平呈显著的相关性;DMF作业工人心电图异常以窦性过缓、过速、窦性心律不齐为主,且中、高浓度组、≥5 a工龄组与对照组差异有统计学意义（P〈0.05）;其次异常为ST-T段改变、不完全性右束支传导阻滞、左心室高电压,虽然这3种心电图异常率随接触DMF浓度和时间而增加,但各组别之间差异均无统计学意义（P〉0.05）。结论 DMF接触浓度与肾功能指标（BUN、Cr）值呈正相关;尿β2-MG可考虑作为急性DMF中毒检测指标之一;尿中NMF含量可作为DMF作业工人的生物监测指标;DMF作业工人心脏功能受到不同程度的影响。     

Measurement of N-methylformamide in occupational exposure to N,N-dimethylformamide

N,N-dimethylformamide (DMF) is a solvent that is widely used in industry. The major occupational sources of exposure results from production of synthetic leather. The main metabolite formed in both man and animals is N-hydroxymethyl-N-methylformamide. Demethylation leads to N-methylformamide (NMF) and formamide and also to a small extent to hydroxy-methylformamide. All the metabolites are excreted in urine, as are very small amounts of the unchanged substance. N-acetyl-S-(N-methyl-carbamoyl)-cysteine can be determined in urine as a further metabolite. We conducted this biomonitoring study with the aim of evaluating the correlation between the excretion of N-methylformamide (mainly from N-hydroxymethylformamide) and levels of exposure to N,N-dimethylformamide among occupationally exposed people. The mean time-weighted average (TWA) exposure was about half (13.5 mg/m3) of the current threshold limit value, the range of the values varying from 0.4 to 75.2 mg/m3. A linear equation existed between urinary NMF concentration and DMF concentration in the environment. The findings show that the urinary NMF concentration can be used as an appropriate biological exposure index. The authors suggest for occupationally exposed subjects, a urinary NMF concentration corresponding to the time-weighted average of the threshold limit value of 39.9 mg/l (37.2 mg/g creatinine) and a 95% lower confidence limit (biological threshold) of 23.4 mg/l (22.2 mg/g creatinine).     

Biological monitoring of occupational exposure to N,N -dimethylformamide – the effects of co-exposure to toluene or dermal exposure

Objectives: The objective of this study is to assess the exposure and intake dose of N,N-dimethylformamide (DMF) and the correlation between them, according to the type of exposure for the workers in the DMF industry. Methods: We monitored 345 workers occupationally exposed to DMF, from 15 workshops in the synthetic fiber, fiber coating, synthetic leather and paint manufacturing industries. Ambient monitoring was carried out with personal samplers to monitor the external exposure. Biological monitoring was done to determine the internal dose by analyzing N-methylformamide (NMF) in end-shift urine. Work procedure and exposure type of each DMF workshop was carefully surveyed, to classify workers by exposure type according to work details. Workers were classified into three groups (Group A: continuous and direct exposure through inhalation and skin; Group B: intermittent and short-term exposure through inhalation and skin; Group C: continuous and indirect exposure mostly through inhalation). Results: Geometric mean of DMF concentration in air was 2.62 (GSD 5.30) ppm and that of NMF in urine was 14.50 (GSD 3.89) mg/l. In the case of continuous absorption through inhalation and dermal exposure (Group A), the value of NMF in urine corresponding to 10 ppm of DMF was 45.3 mg/l (r=0.524, n=178), 39.1 mg/g creatinine (r=0.424), while it was 37.7 mg/l (r=0.788, n=37), 24.2 mg/g creatinine (r=0.743) in the case of absorption mostly through inhalation (Group C). Creatinine correction reduced the correlation between two parameters. Conclusion: The NMF in urine corresponding to 10 ppm DMF, of the dermal and inhalation exposure group was 39.1 mg/g creatinine (r=0.424, n=178), while that of the inhalation exposure-only group was 24.2 mg/g creatinine (r=0.743, n=37). Co-exposure with toluene reduced the NMF excretion in urine. Received: 4 October 1999 / Accepted: 25 April 2000     

Insertion polymorphism of CYP2E1 and urinary N -methylformamide after N,N - dimethylformamide exposure in Japanese workers

Objectives: This study examined whether consideration of the *1C/*1D CYP2E1 insertion polymorphism is important for interpreting the biological monitoring of exposure to N,N-dimethylformamide (DMF) in Japanese workers. Methods: The insertion genotype, airborne DMF exposure on the last day of a work week, and NMF in urine sampled just after the last workshift of the week were determined in 44 male and female Japanese workers. Results and conclusions: The allelic frequency of this CYP2E1 polymorphism was 0.261 in this Japanese population of workers. The CYP2E1 insertion polymorphism did not contribute to NMF levels even after consideration of BMI or alcohol intake. The results indicate that CYP2E1 insertion polymorphism does not appear to be an important determinant for the interpretation of biological exposure to DMF by the measurement of urinary NMF. Received: 26 September 2000 / Accepted: 7 May 2001     

Liver function alterations in synthetic leather workers exposed to dimethylformamide

A cross-sectional study of the prevalence of chronic liver function alterations was performed in 75 workers employed in a synthetic leather factory, exposed to dimethylformamide (DMF) air concentrations below threshold limit values (30 mg/m³). Biological monitoring among workers revealed acceptable urine levels of monomethylformamide (NMF) on average, but the very wide range indicated that occasional overexposure was possible. The worker survey showed a high percentage of disulfiram-like symptoms (50%) and liver function abnormalities (22.7%), compared with a demographically similar group of unexposed workers. Covariance analysis (ANCOVA) revealed that enzyme levels were significantly higher in exposed workers than in controls after data were corrected for age, alcohol consumption, body mass index, and cholesterol levels. The authors conclude that DMF can cause liver diseases even if air TLVs are respected, because accidental contact with liquid DMF can significantly increase DMF uptake. In this situation, air monitoring is no longer sufficient to evaluate worker exposure. Am. J. Ind. Med. 32:255-260, 1997. © 1997 Wiley-Liss, Inc.     

Biological monitoring and exposure to mercury

Occupational health professionals' interest in controlling mercury (Hg) exposure, and the use of biological monitoring in this context, has been ongoing for a number of years. Evidence from urinary Hg results in a number of UK firms who have undertaken some form of biological monitoring or occupational health surveillance suggest that exposure has decreased over the last 10-15 years. This decrease precedes the establishment in the UK of an advisory biological monitoring guidance value (HGV) for urinary Hg and the production of updated medical guidance from the Health & Safety Executive on Hg exposure (MS12 1996). This latter document recommends a urinary sampling interval for urinary Hg of between 1 and 3 months, which is consistent with the reported toxicokinetics of Hg excretion, but we highlight that urinary Hg represents integrated exposure over many previous months. Mercury is a recognized nephrotoxin and MS12 1996 mentions the use of regular dipstick protein estimations. We review our experience of investigating proteinuria and enzymuria in a large-scale cross-sectional occupational study. The incidence of Hg-induced renal disease is probably very rare at current exposure levels. Therefore acceptance of a high false-positive rate of proteinuria not related to Hg exposure needs to be considered in any urinary protein testing regime of Hg workers. The establishment of an HGV for urinary Hg has raised questions about the uncertainty associated with a urinary Hg result, including factors such as diurnal variation, whether urine correction by creatinine or specific gravity is preferable and the possibility of non-occupational sources of Hg contributing significantly towards breaching the HGV. Correction of urinary Hg results by creatinine or specific gravity and the use of a fixed sampling time, such as the beginning or end of the day, substantially reduce the uncertainty in a urinary Hg measurement. But even with good laboratory precision, an individual with a true urinary Hg excretion of 20 nmol/mmol creatinine could supply urine samples of between 14 and 26 nmol/mmol creatinine. The influence of dietary sources in the UK contributing to urinary Hg values approaching or exceeding the HGV is unlikely. The use of tribal or ethnic cosmetics and remedies needs to be considered if a urinary Hg result looks inappropriately high, as some such preparations have been found to contain Hg and can be absorbed through the skin. The ability of excessive chewers or teeth grinders who have a large number of dental amalgam fillings to breach the urinary HGV in the absence of substantial occupational Hg exposure has been reported in a few Scandanavian studies. We report here a likely case of this phenomenon. Since the establishment of the HGV, our biological monitoring Hg data from a number of industry sectors using inorganic or metallic Hg have suggested that a minority of samples (13%) are still greater than the HGV.     

Evaluation of current biological exposure index for occupational N, N-dimethylformamide exposure from synthetic leather workers

The aim of this study was (1) to investigate the correlation between external exposure to N, N-dimethylformamide (DMF) and urinary excretion of DMF and N-methylformamide; (2) to assess whether the correspondence between the current occupational exposure limit setting and recommended urinary biological exposure index is substantial; and (3) to evaluate whether coexposure to toluene, methyl ethyl ketone, and ethyl acetate has an effect on urinary excretion of DMF and N-methylformamide (NMF). Urinary DMF and NMF were significantly correlated (P < 0.01) with one another and also significantly correlated with airborne DMF (P < 0.01) over the range of 1.55 to 152.8 mg/m. Urinary DMF can be considered a complementary marker for short-term exposure. Urinary concentration of NMF and DMF, corresponding to the 8-hour exposure to airborne DMF at 30 mg/m, was estimated to 38.4 mg/L or 39.4 mg/g creatinine for NMF and to 0.92 mg/L or 0.96 mg/g creatinine for DMF.     

The effects of co-exposure to methyl ethyl ketone on the biological monitoring of occupational exposure to<Emphasis Type="Italic"> N,N</Emphasis>-dimethylformamide

OBJECTIVES: (1) To assess whether urinary N,N-dimethylformamide (U-DMF) is suitable as a biomarker when co-exposure to methyl ethyl ketone (MEK) exists, and to evaluate whether it is suitable as an exposure biomarker of DMF. (2) To examine whether the co-exposure to MEK affects the characteristics of U-NMF and U-DMF. (3) To investigate if the difference in creatinine-adjusted and non-adjusted measurements of urinary biomarkers of DMF exposure is substantial. METHODS: Personal exposure monitoring of N,N-dimethylformamide (DMF) and MEK on 11 synthetic-leather workers was performed for 5 consecutive days. Daily post-shift urine for each individual was collected and was analyzed for urinary N-methylformamide (U-NMF) and U-DMF levels on both non-adjusted and creatinine-adjusted bases. RESULTS: Both U-NMF and U-DMF showed significant associations with airborne DMF. Positive and significant associations between U-NMF and U-DMF on either a non-adjusted basis or a creatinine-adjusted basis were found. Satisfactory linear associations ( P<0.01) between all kinds of urinary biomarkers and DMF exposure were found. The co-exposure to MEK exerted more effect on the relationship of airborne DMF to U-DMF than to U-NMF. CONCLUSIONS: U-DMF is detectable when occupational DMF exposure is near or below the occupational exposure limit of 10 ppm. In view of the performance of sensitivity, specificity, and positive predictive value, U-NMF, in general, is superior to U-DMF. However, on a par with other findings in this and previous studies, U-DMF might be considered as a complimentary biomarker of exposure to DMF in addition to U-NMF. No distinction between creatinine-adjustment or non-adjustment for urine specimens was found in the biological monitoring of DMF exposure. Further exploration of the influence of co-exposure to MEK at higher exposure is warranted.     

The use of biomarkers of exposure of N,N-dimethylformamide in health risk assessment and occupational hygiene in the polyacrylic fibre industry

Background: N,N-dimethylformamide (DMF) was recently prioritised for field studies by the National Toxicology Program based on the potency of its reproductive toxic effects.

Aims: To measure accurately exposure to DMF in occupational settings.

Methods: In 35 healthy workers employed in the polyacrylic fibre industry, N-methylformamide (NMF) and N-acetyl-S-(N-methylcarbamoyl)cysteine (AMCC) in urine, and N-methylcarbamoylated haemoglobin (NMHb) in blood were measured. Workplace documentation and questionnaire information were used to categorise workers in groups exposed to low, medium, and high concentrations of DMF.

Results: All three biomarkers can be used to identify occupational exposure to DMF. However, only the analysis of NMHb could accurately distinguish between workers exposed to different concentrations of DMF. The median concentrations were determined to be 55.1, 122.8, and 152.6 nmol/g globin in workers exposed to low, medium, and high concentrations of DMF, respectively. It was possible by the use of NMHb to identify all working tasks with increased exposure to DMF. While fibre crimpers were found to be least exposed to DMF, persons washing, dyeing, or towing the fibres were found to be highly exposed to DMF. In addition, NMHb measurements were capable of uncovering working tasks, which previously were not associated with increased exposure to DMF; for example, the person preparing the fibre forming solution.

Conclusions: Measurement of NMHb in blood is recommended rather than measurement of NMF and AMCC in urine to accurately assess exposure to DMF in health risk assessment. However, NMF and AMCC are useful biomarkers for occupational hygiene intervention. Further investigations regarding toxicity of DMF should focus on highly exposed persons in the polyacrylic fibre industry. Additional measurements in occupational settings other than the polyacrylic fibre industry are also recommended, since the population at risk and the production volume of DMF are high.

     

接触二甲基甲酰胺工人经皮暴露干预措施效果评价

目的 探讨聚氨酯合成革工人DMF经皮暴露的干预效果.方法 对聚氨酯合成革企业在职业卫生调查的基础上,选择3个工种5个岗位的26名接触二甲基甲酰胺(DMF)工人为观察对象,采取加强个人防护、工程防护及健康促进等干预措施,观察6个月,对工作场所空气中DMF浓度、手部漂洗液中DMF和工人班末尿中甲基甲酰胺(NMF)含量采用气相色谱法进行测定,比较干预前后指标的变化.结果 干预前,空气中DMF平均TWA为(63.27±52.67)mg/m3合格率为26.9%(7/26),尿中NMF平均浓度为(2.07±0.32)mg/g肌酐,手部漂洗法液中DMF平均含量为(0.88±0.40)mg.干预后,工作场所空气中DMF平均TWA为(29.95±23.79)mg/m3,合格率为53.8%(14/26),工作场所空气中DMF浓度下降了52.7%,与干预前比较,差异有统计学意义(P<0.01);尿中NMF平均浓度为(1.70±0.29)mg/g肌酐,尿中NMF含量下降了17.9%,与干预前比较,差异有统计学意义(P<0.04);手部漂洗法液中DMF平均含量为(0.41±0.81)mg,下降了53.4%,与干预前比较,差异有统计学意义(P<0.05).结论 对于合成革工人DMF经皮暴露采取工程控制、个体防护和健康促进的综合性干预措施,能达到有效控制的目的.

Abstract：

Objective To assess the effects of interventions on synthetic leather workers exposed to N,N-dimethylformamide (DMF) by skin.Methods Twenty-six workers exposed to DMF were recruited.The level of DMF in ambient or handwash solution and N-methylformamide (NMF) in end-shift urine samples were detected before interventions and after interventions for six months.Results After interventions the levels of DMF in ambient reduced 52.7 % from (63.27±52.67) mg/m3 to (29.95±23.79) mg/m3.The levels of NMF in urine samples reduced 17.9% from (2.07±0.32) mg/g Cr to (1.70±0.29) mg/g Cr (P<0.01).The mean level of DMF in handwash solution reduced 53.4% from 0.88±0.40 mg to 0.41±0.81 mg.Conclusion This study showed that the multi-intervention measures (engineering control,personal protection and health promotion) should be used for the synthetic leather workers occupationally exposed to DMF.