Most cited article - PubMed ID 1399028
Absorption, metabolism and elimination of N,N-dimethylformamide in humans
The metabolism and toxicokinetics of cyclohexanone (CH-one), an important solvent and chemical intermediate, have been studied in volunteers during and after 8-h exposures to CH-one vapour at a concentration of 101, 207 and 406 mg.m-3. The pulmonary ventilation in these experiments was typically 11 l.min-1 and retention in the respiratory tract was 58%. After exposure to CH-one, 207 mg.m-3, the metabolic yields of cyclohexanol (CH-ol), 1,2- and 1,4-cyclohexanediol (CH-diol) as determined in urine by a gas chromatographic method involving hydrolysis of glucuronide conjugate were 1.0% +/- 0.3%, 39% +/- 5% and 18% +/- 2% (n = 8), respectively. Peak excretion of CH-ol was achieved at the end of the exposure period, after which it decayed rapidly. Elimination of 1,2- and 1,4-CH-diol reached maximum values a few hours following exposure, with subsequent elimination half-times of 16 +/- 2 and 18 +/- 4 h, respectively. Repeated exposure to CH-one vapour (around 200 mg.m-3) for five consecutive days (8 h/day) resulted in cumulative excretion of CH-diols. The permeation rate of CH-one liquid through the skin was 0.037-0.069 mg.cm-2.h-1 (n = 3), indicating that the contribution of percutaneous absorption to total CH-one occupational intake is of minor importance. CH-diols are recommended as biomarkers of exposure to CH-one.
- MeSH
- Administration, Inhalation MeSH
- Administration, Cutaneous MeSH
- Biomarkers MeSH
- Cyclohexanols metabolism MeSH
- Cyclohexanones metabolism pharmacokinetics urine MeSH
- Adult MeSH
- Respiration physiology MeSH
- Skin Absorption physiology MeSH
- Air Pollutants metabolism pharmacokinetics urine MeSH
- Middle Aged MeSH
- Humans MeSH
- Environmental Monitoring methods MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Biomarkers MeSH
- Cyclohexanols MeSH
- Cyclohexanones MeSH
- Air Pollutants MeSH
Skin penetration fo N,N-dimethylformamide (DMF) liquid or vapour was studied in volunteers. Exposure to liquid DMF was performed in two ways: in a "dipping experiment", one hand was dipped up to the wrist in DMF for 2-20 min, while in a "patch experiment", 2 mmol DMF was applied to the skin and allowed to be absorbed completely. The period of exposure to DMF vapour (50 mg.m-3) was 4 h. The DMF metabolites N-hydroxymethyl-N-methylformamide ("MF"), N-hydroxymethylformamide ("F"), and N-acetyl-S-(N-methylcarbamoyl)cysteine (AMCC) were monitored in the urine. Liquid DMF was absorbed through the skin at a rate of 9.4 mg.cm-2.h-1. Percutaneous absorption of DMF vapour depended strongly on ambient temperature and humidity and accounted for 13%-36% of totally excreted "MF". The results suggest that skin absorption of liquid DMF is likely to contribute to occupational exposure substantially more than penetration of DMF vapour. The yield of metabolites after transdermal DMF absorption was only half of that seen after pulmonary absorption. Elimination of "MF" and "F" but not that of AMCC was delayed, which supports the contention that AMCC should be used instead of "MF" as the most suitable biomarker of DMF in cases where percutaneous intake can occur.
- MeSH
- Acetylcysteine analogs & derivatives urine MeSH
- Dimethylformamide analogs & derivatives chemistry metabolism pharmacokinetics MeSH
- Adult MeSH
- Formamides metabolism MeSH
- Skin Absorption * MeSH
- Middle Aged MeSH
- Humans MeSH
- Gases MeSH
- Solvents chemistry metabolism pharmacokinetics MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Acetylcysteine MeSH
- Dimethylformamide MeSH
- Formamides MeSH
- N-acetyl-S-(N-methylcarbamoyl)cysteine MeSH Browser
- N-hydroxymethyl-N-methylformamide MeSH Browser
- N-hydroxymethylformamide MeSH Browser
- Gases MeSH
- Solvents MeSH