DMF Exposure Research Articles

Chemometric analysis of N,N-dimethyl formamide-induced phytotoxicity in rice seedlings

Physiological responses of rice (Oryza sativa L. cv. XZX 45) seedlings to N,N-dimethyl formamide (DMF) were evaluated using chemometric modeling. Thirteen selected physiological parameters of the plants were monitored to evaluate the phytotoxicity from DMF exposure. The data matrix was further treated with cluster analysis and principal component analysis (PCA). Cluster analysis (CA) rendered two distinct clusters, suggesting different responses to DMF exposure between the root and shoot. PCA results suggested that relative growth rate (RGR), water use efficiency (WUE), malondialdehyde (MDA), soluble sugar (SS), proline, protein, Evan blue uptake (EBU), catalase (CAT), and peroxidase (POD) were dominant in root tissues, whereas carotenoids and total chlorophyll were most common in the shoot of DMF-treated rice seedlings. Additionally, analysis of red list index (RLI) was conducted to calculate the sensitivity index among all selected parameters in the shoots and roots at DMF EC10 and EC50 concentrations. The most sensitive parameter to DMF exposure in the shoots was proline and RGR at EC50 concentration, whereas it was EBU in root tissues. Superoxide dismutase (SOD) and CAT activities were the most sensitive parameters to DMF stress in the roots and shoots at EC10 concentration, respectively. Chemometric analysis suggested that DMF exposure caused phytotoxic stress to young rice seedlings, but plant tissues responded differently.

Effectiveness and Safety of Dimethyl Fumarate Treatment in Relapsing Multiple Sclerosis Patients: Real-World Evidence.

IntroductionDimethyl fumarate (DMF) has been recently approved as a disease-modifying therapy for the treatment of multiple sclerosis (MS). Post-marketing studies are important to confirm what was established in clinical trials.ObjectiveTo evaluate effectiveness and safety of DMF and to measure the occurrence of lymphopenia in a cohort of MS patients in a clinical setting.MethodsUsing the national MS registry, we prospectively assessed relapsing MS patients who had been prescribed DMF for at least 6 months. Primary outcome measure was the proportion of relapse-free patients at last follow-up visit. Secondary outcome measures were the mean change in expanded disability status scale (EDSS) and the proportion of patients with radiological activity (gadolinium-enhancing or new T2 lesions) at the last follow-up visit. Absolute lymphocyte count (ALC) was assessed at baseline (within 6 months prior to DMF initiation) and at one or more times during DMF treatment 3 months post-initiation.ResultsOf 134 patients identified, 119 were eligible and included in the analysis. Women represented 59.7% of the studied cohort. Mean age and mean disease duration were 33.5 ± 11.1 and 8.3 ± 7 years, respectively. A total of 75.6% of the patients received prior disease-modifying therapies. Mean duration of DMF exposure was 20.5 ± 9.5 months. The proportion of relapse-free patients increased significantly from 51.2% to 89.9% (p < 0.0001), while the mean EDSS score decreased from 2.8 ± 1.8 at baseline to 2.3 ± 1.7 (p < 0.058) at last follow-up visit. The proportion of patients with MRI activity decreased significantly from 61.1% to 15.1% (p < 0.0001). The mean ALCs decreased from 2170 to 1430 cells/μl (34% decrease). Lymphopenia was seen in 13 (10.9%) patients, of whom 3 (2.5%) patients had grade 3 lymphopenia necessitating discontinuation of DMF. Although no serious adverse events were reported, 19.3% of patients discontinued DMF.ConclusionIn clinical practice, DMF appeared to be effective in reducing disease activity and progression of disability throughout the observational period. DMF was well tolerated with no serious adverse events. ALC profiles in DMF-treated patients were generally stable throughout the observational period. The proportion of patients who developed severe lymphopenia was similar to figures in clinical trials.

Study on apoptosis mechanism of H9c2 cardiomyocytes induced by N, N-dimethylformamide

Objective: To observe the change levels of nuclear factor-kappa B (NF-κB) p65 protein in cytoplasm and nuclear, phosphorylation of inhibitor of kappa B (p-IκB) protein and cytochrome C (Cyt-c) , cleaved cysteinyl aspartate specific proteinase-3 (Cleaved caspase-3) , B-cell lymphoma/leukemia-2 (Bcl-2) in cytoplasm in the process of N, N-dimethylformamide (DMF) -induced apoptosis in H9c2 cardiomyocytes, and explore the tentative mechanism of apoptosis. Methods: H9c2 cardiomyocytes were exposed to 200 mmol/L DMF. Western blotting was used to detect the protein expression levels of p65 in cytoplasm and nuclear, p-IκB after exposure for 0, 2, 4, 6, 8, 12 h, and the protein expression levels of Cyt-c, Cleaved caspase-3, Bcl-2 in cytoplasm after exposure for 0, 2, 4, 8, 12, 24 h. Immunofluorescencecytochemistry (IFC) was used to observe the location of Cyt-c after 200 mmol/L DMF exposure for different times. Results: The levels of p65 in cytoplasm and nuclear and p-IκB among groups were statistically significant (F were 7.79, 33.11, 90.25, respectively, all P<0.01) . Compared with the control group, the levels of p65 in cytoplasm of 2, 4, 6 h group were significantly decreased (all P<0.01) ; the levels of p65 in nuclear of 2, 4, 6, 8 h were significantly increased (all P<0.01) ; the levels of p-IκB of 2, 4, 6 h group were significantly increased (all P<0.01) . The levels of Cyt-c, Cleaved caspase-3 and Bcl-2 among groups were statistically significant (F were 51.42, 503.68, 73.37, respectively, all P<0.01) . Compared with the control group, the levels of Cyt-c of 8, 12 h group were significantly increased (both P<0.01) ; the levels of Cleaved caspase-3 of 2, 4, 8, 12, 24 h were significantly increased (all P<0.01) ; the levels of Bcl-2 of 2, 4, 8, 12, 24 h group were significantly decreased (all P<0.01) . IFC showed that Cyt-c was released from the mitochondria to the cytoplasm gradually as the extension of the exposure time. Conclusion: NF-κB signaling pathway and mitochondrial pathway are involved in the mechanism of DMF-induced apoptosis in H9c2 cardiomyocytes.

Alteration of gut microbial community after N,N-Dimethylformamide exposure.

N,N-Dimethylformamide (DMF), a solvent commonly used in factories, can induce liver toxicities, including hepatitis, fibrosis, cirrhosis and hepatoma. It is well known that the gut microbial community plays a role in the metabolism of many toxic substance and in liver regeneration. However, the effect of DMF on rat gut microbial community is poorly understood. The gut microbiotas in control rats and rats exposed to DMF were characterized by high-throughput sequencing of the bacterial 16S rRNA gene. The levels of biochemical parameters in the serum of rats, including cholesterol, bile acid, alanine aminotransferase (ALT), and aspartate aminotransferase (AST), were evaluated. The weight was lower in the DMF exposure group than in the control group. DMF exposure led to changes in gut microbiotas that were reflected in a decreased abundance of Prevotellaceae, Lactobacillaceae, and increased abundance of S24-7, Baceroidaceae, Rikenellaceae and Peptostreptococcaceae. Compared with control group, the cholesterol level was substantially reduced in the DMF exposure group (p < 0.05), while the concentration of bile acid was significantly increased in the DMF exposure group (p < 0.05). The present data established that the gut microbiotasy were changed after DMF exposure, and it revealed the relationship between DMF and gut microbiotas for the first time.

Cross-sectional study on N,N-dimethylformamide (DMF); effects on liver and alcohol intolerance.

There are still concerns regarding occupational exposure to hepatotoxic DMF. This study was designed to evaluate possible liver damaging effects of DMF under current workplace conditions in synthetic fibres industries. Among other laboratory parameters, liver function parameters (alkaline phosphatase (ALP), aspartate aminotransferase, alanine aminotransferase and gamma-glutamyltransferase), the mean corpuscular erythrocyte volume (MCV) and carbohydrate-deficient transferrin (CDT) of the workforce of two companies present at the days of study were investigated. Internal exposure to DMF was assessed via three different biomarkers [sum of N-methylformamide and N-hydroxymethyl-N-methylformamide, N-acetyl-S-(N-carbamoyl)cysteine (AMCC) and 3-methyl-5-isopropylhydantoin (MIH)]. Alcohol consumption was assessed by means of direct ethanol metabolites (ethylglucuronide and ethylsulfate). None of the tested liver enzyme activities showed a positive association with any of the three exposure markers, nor did CDT and MCV. CDT was negatively associated with AMCC and the ALP activity negatively with all three exposure markers. Changes in liver function are seen mainly in conjunction with ethanol consumption but also with increasing body weight and age. MCV was associated with smoking. Almost half of the workers stated to experience alcohol flush reaction. The present study indicates that long-term exposure to DMF, which was specified by median urinary AMCC levels of 4.84mg/g creatinine and DMF haemoglobin adduct levels of 60.5nmol/MIH/g globin, respectively, does not result in any adverse liver effects. In contrast, these DMF exposure levels still elicit certain alcohol intolerance reactions.

Inhibition of lymphocyte VLA-4 expression by DMF exposure in experimental autoimmune encephalomyelitis (EAE) (P2.188)

Inhibition of lymphocyte VLA-4 expression by DMF exposure in experimental autoimmune encephalomyelitis (EAE) (P2.188)

Toxicity of intragastrically administered N, N-dimethylformamide in female Wistar rats

To investigate the toxicity of intragastrically administered N, N-dimethylformamide (DMF) in female Wistar rats, and to provide experimental data for the overall evaluation of DMF toxicity under different ways of exposure. Forty female Wistar rats weighing 150∼180 g were randomly divided into four groups: control group (treated with water) and three DMF exposure groups with doses of 50 mg/kg, 100 mg/kg, and 200 mg/kg. After oral administration of DMF once a day for 14 consecutive days, the rats were weighed and sacrificed. The liver, kidney, brain, and uterus were weighed to calculate organ indices. The pathological changes in the liver were examined by HE staining. The protein expression of HSP70 in the liver, kidney, and brain was determined. Finally, peripheral lymphocytes were collected from the arteria cruralis to determine DNA damage by comet assay. Fourteen days after DMF exposure, the body weight and organ indices of the kidney, brain, and uterus showed no significant changes. However, the liver index showed concentration-dependent increase in all DMF exposed groups (3.52±0.21, 3.55±0.13, and 3.88±0.22 in the low-, medium-, and high-dose groups, respectively), as compared with the control group (3.24±0.28) (P < 0.05 or P < 0.01). The pathological damage in the liver also showed a concentration-dependent manner. Inflammatory cell infiltration and granular degeneration in centrilobular hepatocytes were observed in the high-dose group. No significant change in protein expression of HSP70 was observed in the liver, kidney, or brain of DMF-exposed rats (P > 0.05). DNA damage was induced by DMF, and the DNA percentage of lymphocyte comet tail, average tail length, and tail moment in exposed groups were all significantly increased as compared with the control group (P < 0.05 or P < 0.01). Gavaged DMF can induce liver injury and DNA damage in lymphocytes in rats 14 days after administration. There is no significant change in protein expression of HSP70 in the liver, brain, or kidney after DMF exposure.

Study of N-methylcarbamoylated hemoglobin in blood of being an exposure biomarker of N, N-dimethylformamide

To assess the value of blood N-methylcarbamoylated haemoglobin (NMHb) as a biomarker of N, N-dimethylformamide (DMF) exposure. Seventy-two DMF processing workers in a synthetic leather factory were included in the DMF exposure group, and 12 workers in a food factory without exposure to DMF were included in the control group. Long-time individual sampling in workplace was performed among 45 workers in the exposure group, accompanied by a questionnaire survey. Blood and urine were collected for the determination of urinary N-methylformamide (NMF), urinary creatinine, and blood NMHb. Air DMF and urinary NMF were determined by gas chromatography. NMHb in blood was degraded to 3-methyl-5-isopropylhydantoin by Edman degradation before it could be determined by gas chromatography/mass spectrometry. Air DMF in workplace and NMF in post-shift urine were both correlated with NMHb in blood, and the respective regression equations were LgNMHb (nmol/g globin) = 0.32×LgDMF (mg/m(3))+1.8 (r = 0.60, P < 0.005), and LgNMHb (nmol/g globin) = 0.47×LgNMF (mg/g Cr) + 1.4 (r = 0.56, P < 0.005). NMHb can be used as a biomarker of long-term exposure to DMF.

Study on the association between residential exposure to N, N-dimethylformamide and hospitalization for respiratory disease

Some studies have confirmed the adverse effects of N, N-dimethylformamide (DMF) on the different organs in occupational exposure workers. However, to the best of our knowledge, risk assessment in the general population has not been available. In this study, a time series analysis of the relationship between DMF exposure and respiratory hospitalization was performed in Longwan district of China in 2008. Generalized additive model (GAMs) reflected that a 101.0 μg m−3 (inter-quartile range) increase in the 1-day lag concentration of DMF resulted in a 1.17 (95% CI: 1.09–1.25) increased relative risk of hospitalization for respiratory problems. The dose–response curve representing the relationship between DMF and the logarithm of the number of hospitalization was adequately linear at 4–200 μg m−3. We proposed a risk on respiratory disease in non-occupational DMF exposure. More information is required to verify this observation and the other endpoints to general population should be investigated during long-term DMF exposure.

Effect of N,N-dimethylformamide on calcium homeostasis and the calpain gene expression in human hepatocytes

To investigate the effect of N,N-dimethylformamide (DMF) on calcium homeostasis and calpain I and II gene expression in human hepatocytes (HL-7702). HL-7702 cells were exposed to different concentrations of DMF (10, 25, 50, 100, or 200 mmol/L); other HL-7702 cells, which were used as a control group, were exposed to the equal volume of DMEM; the intracellular Ca(2+) concentration was monitored using the calcium fluorescent probe (fluo-3/AM). After 24-h exposure to DMF (10, 25, 50, 100, 150, or 200 mmol/L), the morphology of hepatocytes was observed under an inverted phase contrast microscope, and the cell viability was measured by MTT assay. After 24-h exposure to DMF (10, 25, 50, 100, or 150 mmol/L), the mRNA expression levels of calpain I and II in hepatocytes were measured by real-time quantitative PCR. There were significant differences in cell viability among different exposure groups (P < 0.01); the 50, 100, 150, and 200 mmol/L DMF exposure groups had a significantly lower cell viability than the control group (P < 0.05). Under the inverted phase contrast microscope, HL-7702 cells gradually lost the original shape, with swelling and shrinking, as the dose of DMF increased, and those treated with 150 mmol/L DMF even became round and floated. The fluorescence density of fluo-3 in hepatocytes increased as the dose of DMF rose, demonstrating a dose-response relationship, and there were significant differences among these exposure groups (P < 0.05). There were significant differences in mRNA expression levels of calpain I and II among these exposure groups (P < 0.01), and the expression increased as the dose of DMF rose; but DMF did not promote the mRNA expression of calpain I at a concentration of 150 mmol/L. DMF can cause damage to hepatocytes, which is related to intracellular calcium increase and calpain mRNA increase.

Clinical Outcomes of Occupational Exposure to N,N-Dimethylformamide: Perspectives from Experimental Toxicology

N,N-Dimethylformamide (DMF) is globally used as an organic solvent in the production of synthetic leather and resins because of its low volatility, making it an attractive industrial material. Despite its excellent property as a chemical solvent, utilization of DMF is somewhat controversial nowadays due to its hazardous effects on exposed workers in work places. Many toxification cases are being reported globally and the number of cases of liver damage is still increasing in developing countries. On account of this, a series of epidemiologic surveys are being conducted to understand the degrees of liver damage caused by DMF exposure. Furthermore, many investigations have been performed to clarify the mechanism of DMF-induced liver toxicity using both human and experimental animal models. This review summarizes the current occupational cases reported on liver damage from workers exposed to DMF in industrial work places and the research results that account for DMF-induced liver failure and possible carcinogenesis. The findings reviewed here show the synergistic toxicity of DMF exposure with other toxicants, which might occur through complicated but distinct mechanisms, which may extend our knowledge for establishing risk assessments of DMF exposure in industrial work places.

Liver and heart toxicity due to 90-day oral exposure of ICR mice to N,N-dimethylformamide

N,N-dimethylformamide (DMF) is a colorless liquid with a faint amine odor, which is widely used in the world. DMF exposure may induce adverse effects on liver, but few studies showed damage to heart after exposure to DMF. In the present study, DMF was administered to ICR mice with the doses of 0.32, 0.63 and 1.26 g/kg of body weight by gavage for 90 days. The increase in the relative liver weight is accompanied with the presence of the centrilobular hepatocellular hypertrophy as well as increased serum levels of aspartate transaminase (AST) and alanine transaminase (ALT). An increase of malondialdehyde (MDA) level was shown in liver homogenate, while superoxide dismutase (SOD) and glutathione (GSH) activities decreased. Heart damage was also shown in mice exposed to DMF for 90 days, although pathological examination showed only slight inflammatory cell infiltration. Increased levels of serum lactate dehydrogenase (LDH), isoenzymes of creatine kinase (CK-MB) and cardiac troponin I (cTnI) were shown. Increased level of MDA was also shown in heart homogenate, in contrast with the decreased activity of SOD. These data suggested that the administration of DMF could induce liver and heart injuries and oxidative stress was involved in the toxic effects.

Occupational Liver Injury Due to N,N-Dimethylformamide in the Synthetics Industry

N,N-dimethylformamide (DMF) is a solvent used extensively in the chemical industry. The main toxic effect reported after exposure to DMF is hepatotoxicity. We encountered four patients with liver injury due to DMF exposure; the severity of the liver injury was related to the exposure levels. After removal of exposure, all patients recovered without specific treatment. A careful evaluation of occupational history is necessary when liver dysfunction develops in industrial workers.

Combining novel strategy with kinetic approach in the determination of respective respiration and skin exposure to N, N-dimethylformamide vapor

Abstract N, N-dimethylformamide (DMF) could be readily absorbed via skin and inhalation routes. It is difficult, however, to separate the internal dose contribution from skin vapor and inhalation exposure. This study attempts to quantitatively determine the separate skin vapor and inhalation exposure contributions using a semi-actual exposure approach. Six volunteers were tailgated by DMF-exposed employees completely for two exposure scenarios: with and without wearing a respirator. Individual airborne DMF (A-DMF) exposure was evaluated by integrating real-time DMF monitoring and time-activity log. Urinary N-methylformamide (U-NMF) concentrations in 4-h and 8-h one urine sample plus 24-h consecutive urine sample were determined to evaluate the internal DMF exposure dose. The average A-DMF concentrations for all participants were 8.10 (2.75) and 9.52 (3.47) ppm, respectively, for with respirator and without respirator scenarios. Area under the curve of U-NMF throughout 24-h showed 71% and 29% contribution from skin and inhalation exposure, respectively, indicates that the absorbed dose of DMF via skin vapor exposure was much greater than inhalation. In conclusion, the semi-actual approach provides a novel measure to accurately determine the relative skin vapor and inhalation exposure contributions to the internal dose. The skin vapor exposure deserves more attention in the prevention of chemical hazards in the exposed environment.

Abnormal liver function associated with occupational exposure to N, N-dimethylformamide in synthetic leathers works

To investigate the hepatotoxic effects of N, N-dimethylformamide (DMF) in the workers of a synthetic leathers factory, and the effects on liver function of covariates such as alcohol consumption and other factors. The workers were classified into three groups (low, high and the control) by the concentration of DMF in workplace which was determined in the past two years. A questionnaire was drawn up for relevant demographic characteristics and other factors influencing liver function. The bloods were collected for laboratory test which included parameters especially relevant to the liver (ALT AST and gamma GT). Low and high-exposure groups were significantly associated with elevated ALT and gamma GT, and high-exposure group was significantly associated with elevated Liver index. Modeling by stepwise regression analysis demonstrated that high concentration of DMF and BMI were associated with and elevated ALT, gamma GT and Liver index, besides DMF and BMI, the elevation of ALT was also associated with high TRIG. AST was only associated with alcohol consumption. The AST/ALT ration < 1 was present in 86.7% of the exposure workers of liver function abnormal. DMF can cause liver function alternations even if air concentration of DMF was below PC-TWA. Besides the levels of DMF exposure, obesity (BMI) and alcohol consumption are covariates alternating liver function. Liver index can be a parameter for assessment liver function, and the AST/ALT ration < 1 may serve as markers of risk in health screening programs.

Mitochondrial DNA alterations in blood of the humans exposed to N,N-dimethylformamide

N,N-Dimethylformamide (DMF) has been widely used in industries because of its extensive miscibility with water and solvents. Its health effects include hepatotoxicity and male reproductoxicity, possibly linked with mitochondrial DNA (mtDNA) alterations including mtDNA common deletion (DeltamtDNA(4977)) and mtDNA copy number. The relationship between DMF exposure and mtDNA alterations, however, has not been postulated yet. The purposes of this study were to investigate whether the DMF exposure is associated with DeltamtDNA(4977) and mtDNA copy number and to evaluate the DMF-derived mtDNA alterations are more associated with exposure to the airborne DMF concentrations or to the levels of two urinary DMF biomarkers of N-methylformamide (NMF) and N-acetyl-S-(N-methylcarbamoryl) cysteine(AMCC). Thirteen DMF-exposed workers and 13 age and seniority-matched control workers in a synthetic leather factory were monitored on their airborne DMF, NMF and AMCC in the urine as well as DeltamtDNA(4977) and mtDNA copy number in blood cells. We found that the frequencies of relative DeltamtDNA(4977) in DMF-exposed group were significantly higher than those in the control group. Moreover, elevation in the proportion of DeltamtDNA(4977) of individuals with high urine AMCC (U-AMCC) and airborne DMF levels were significantly higher than those without. We conclude that long-term exposure to DMF is highly associated with the alterations of mtDNA in urine and blood cells. The DeltamtDNA(4977) was more significantly related to repeated exposure to DMF and mtDNA copy number was more closely related to short-term DMF exposure. We also confirmed that U-AMCC is more appropriate to serve as a toxicity biomarker for DMF exposure than U-NMF. Further study with a larger number of subjects is warranted.

Mitochondrial DNA Damage in Humans Occupationally Exposed to N,N-dimethylformamide

P-740 Abstract: N,N-dimethylformamide (DMF) has been widely used in many industries because of its extensive miscibility with water and most common solvents. Major documented health effects include hepatotoxicity and male reproductive impairment, possibly linked with mitochondrial DNA (mtDNA) defects including mtDNA 4,977-bp deletion (ΔmtDNA4977) and mtDNA copy number based on the findings of the recent studies. Two major DMF metabolites in urine, N-methylformamide (NMF) and N-acetyl-S-(N-methylcarbamoryl) cysteine (AMCC), have long been used as the biomarkers to reflect the DMF exposure for the humans occupationally exposed to DMF. The relationship between DMF exposure and mtDNA damage, however, has not been postulated yet. The purposes of this study were to investigate the relations of ΔmtDNA4977 and mtDNA copy number to DMF exposure and to evaluate which biomarker could be more relevant to DMF-derived toxicity. The blood samples from 13 DMF-exposed workers and 13 age-seniority-matched non-exposed workers (all male) were collected, and both ΔmtDNA4977 and mtDNA copy number analyses were achieved by real-time quantitative polymerase chain reaction (real-time qPCR). We found the frequencies of relative ΔmtDNA4977 in DMF-exposed group were significantly higher than those in the control group (p=0.01). Moreover, the frequencies of relative ΔmtDNA4977 for those airborne concentrations greater than permissible exposure limit (PEL) were significantly higher than those not. For the biomarker of AMCC, we found the frequencies of relative ΔmtDNA4977 for those with higher urinary AMCC concentrations were significantly greater than those with lower. No any significant findings were observed, however, for the biomarker of NMF. Similar trend was found for mtDNA copy number although no any significant differences were observed. We concluded that long-term exposure to DMF might cause the damage of mtDNA and the ΔmtDNA4977 could be more susceptible than mtDNA copy number with respect to DMF-derived toxicity. We also affirmed that AMCC could be more appropriate in serving as a toxicity biomarker for DMF exposure than NMF.

Using Sem-actual Exposure Approach to the Estimating Respective Contribution of N,N-dimethylformamide (DMF) Exposure via Inhalation and Skin Routes

P-768 Abstract: N,N-dimethylformamide (DMF) has been recommended by National Toxicology Program (NTP) as one of four chemicals with the highest priority for field study. Cumulative evidences have shown that the major exposure routes of DMF uptake for the humans in occupational settings are via inhalation and skin. It is difficult, however, to make a clear distinction of the separate contribution to the body burden between skin vapor exposure and liquid contact for dermal exposure. The purpose of this study was to quantitatively determine relative contribution of skin vapor and inhalation exposure, respectively, by using a semi-actual exposure approach in a synthetic leather factory. Six healthy volunteers were designated to simultaneously move with the actual DMF-exposed employees across a whole work shift for two exposure scenarios: with (skin vapor exposure only) and without (skin vapor plus respiratory exposure) wearing respiratory protection equipment. Airborne exposure assessment was conducted by integrating real-time DMF monitoring and time-activity pattern (TAP) for each individual. Biological monitoring was achieved to collect each participant's urine at pre- and post-shifts as well as 36 hours after exposure, respectively and urinary DMF and N-methylformamide (NMF) were determined as biological exposure markers for the determination of body burden of DMF exposure. We found the time-weighted average of airborne DMF concentrations among all participants by the integration of real-time monitor and TAP were 8.10 (2.75) and 9.52 (3.47) ppm (GM(GSD)), respectively, for skin vapor exposure only and skin vapor plus respiratory exposure. Area under curve (AUC) of urinary NMF throughout 36 hrs showed 47% and 53% of excretory NMF contributed to respiratory exposure and dermal exposure, respectively, indicating that the absorbed dose of DMF via dermal vapor exposure was even greater than that via respiratory exposure. We suggested that skin exposure protection should be enhanced for those who occupationally exposed to DMF in addition to the respiratory protection.

Environmental monitoring of occupational exposure to N,N-dimethylformamide: comparison between active and diffusive sampling

The objective of this study is to optimize the evaluation of the exposure to N,N-dimethylformamide (DMF) in synthetic leather factories by diffusive samplers. The DMF exposure was monitored in synthetic leather factories by two sampler types: active and diffusive. Air measurements were carried out using two different personal air samplers, a diffusive and an active one. The diffusive sampling method, TK200 with charcoal filters, was examined in comparison with pumping through NIOSH silica gel tubes workplace air as with the currently available "gold standard". The evaluation was carried out, in two different years but in the same season, for all the duration of the shift, i.e. 8 h on workers employed in five different factories in the district of Florence and Prato (Italy). The statistical and graphical analysis of data show a good correlation between active and passive samplers (r = 0.96, P < 0.001, n = 91), a good linear regression (DMF(diffusive )= 0.95 DMF(active) + 0.15, R (2) = 0.92), a not statistically significant difference between data (tested by paired t test and non-parametric Wilcoxon test). Moreover, all these results are confirmed for data lower and higher than TLV-TWA, in particular we found a significant Pearson correlation (r = 0.92, P < 0.001, n = 83; r = 0.92, P < 0.05, n = 8, respectively) and a significant linear regression (DMF(diffusive )= 0.88 DMF(active) + 0.73, R (2 )= 0.86; DMF(diffusive )= 0.90 DMF(active) + 3.76, R (2 )= 0.85). Besides, the analysis of graphical representations confirmed the previous evidences. Finally, we can not find a significant difference between different types of job. Due to the good agreement between the two groups of data, the TK200 samplers can be considered as a simpler approach than the pump for screening worker exposures to DMF.

Total body burden arising from a week’s repeated dermal exposure to N,N-dimethylformamide

Background: Hazardous chemicals and their metabolites may accumulate in the body following repeated airborne exposures and skin contact. Aims: To estimate the contribution of skin absorption to total body burden...