title: Biological monitoring of workers exposed to N,N-dimethylformamide in the synthetic fibre industry.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Institut und Poliklinik für Arbeits-, Sozial- und Umweltmedizin, Friedrich-Alexander Universität, Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: H U
authors.initials: HU
authors.lastname: Käfferlein
authors.forename: T
authors.initials: T
authors.lastname: Göen
authors.forename: J
authors.initials: J
authors.lastname: Müller
authors.forename: R
authors.initials: R
authors.lastname: Wrbitzky
authors.forename: J
authors.initials: J
authors.lastname: Angerer
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000633:toxicity; D015415:Biomarkers; D002617:Chemical Industry; D002849:Chromatography, Gas; D004126:Dimethylformamide / Q000009:adverse effects* / Q000032:analysis / Q000493:pharmacokinetics; D005559:Formamides / Q000493:pharmacokinetics / Q000633:toxicity; D006801:Humans; D008297:Male; D016273:Occupational Exposure; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; D005559:Formamides; C052469:N-acetyl-S-(N-methylcarbamoyl)cysteine; D004126:Dimethylformamide; D000111:Acetylcysteine; C002950:methylformamide