Analysis of metabolites of N,N-dimethylformamide in urine samples

To assess the suitability of different methods for biological monitoring of internal dose to N,N-dimethylformamide (DMF) in occupational settings.

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.

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%).

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.