Dimethylformamide pharmacokinetics following inhalation exposure in monkeys. 1993

S G Hundley, and K T McCooey, and P H Lieder, and M E Hurtt, and G L Kennedy
E. I. du Pont de Nemours & Company, Inc., Haskell Laboratory for Toxicology and Industrial Medicine, Newark, Delaware 19714.

Male and female cynomolgus monkeys received whole-body inhalation exposures to dimethylformamide (DMF) at concentrations of 30, 100, and 500 ppm for 6 hours a day, 5 days a week over a 13-week period. Serial blood samples were drawn at the conclusion of the first day of exposure and following 15, 29, 57, and 85 days of testing. Area under the plasma concentration curve (AUC) values were determined for DMF and "NMF" [N-methylformamide (NMF) plus N-(hydroxymethyl)-N-methylformamide (DMF-OH)]. Urine samples were also collected and assayed for DMF, NMF and DMF-OH. The systemic exposure to DMF increased disproportionately as the airborne DMF concentrations increased. DMF AUC values increased 19- to 37-fold in male and 35- to 54-fold in female monkeys as the inhalation concentrations increased 5-fold (100 to 500 ppm). These data are consistent with saturation of DMF metabolism as inhaled DMF concentrations increased from 100 to 500 ppm. AUC values, peak plasma concentrations, and plasma half-lives were essentially unaltered over the duration of the study within each exposure concentration tested. Estimated plasma half-lives ranged from 1 to 2 hours and 4 to 15 hours for DMF and "NMF" respectively. DMF was rapidly converted to "NMF" following 30 ppm exposures, with "NMF" plasma concentrations higher than DMF plasma concentrations at the 0.5 hour time-point. In plasma samples simultaneously assayed for DMF-OH and NMF, the concentration of DMF-OH exceeded, was equal to, or was less than NMF concentrations depending upon the plasma sample. DMF-OH was always the main urinary metabolite (56 to 95 percent) regardless of exposure level or time on study.

UI MeSH Term Description Entries
D008252 Macaca fascicularis A species of the genus MACACA which typically lives near the coast in tidal creeks and mangrove swamps primarily on the islands of the Malay peninsula. Burmese Long-Tailed Macaque,Crab-Eating Monkey,Cynomolgus Monkey,M. f. aurea,M. fascicularis,Macaca fascicularis aurea,Monkey, Crab-Eating,Monkey, Cynomolgus,Crab-Eating Macaque,Burmese Long Tailed Macaque,Crab Eating Macaque,Crab Eating Monkey,Crab-Eating Macaques,Crab-Eating Monkeys,Cynomolgus Monkeys,Long-Tailed Macaque, Burmese,Macaque, Burmese Long-Tailed,Macaque, Crab-Eating,Monkey, Crab Eating
D008297 Male Males
D002849 Chromatography, Gas Fractionation of a vaporized sample as a consequence of partition between a mobile gaseous phase and a stationary phase held in a column. Two types are gas-solid chromatography, where the fixed phase is a solid, and gas-liquid, in which the stationary phase is a nonvolatile liquid supported on an inert solid matrix. Chromatography, Gas-Liquid,Gas Chromatography,Chromatographies, Gas,Chromatographies, Gas-Liquid,Chromatography, Gas Liquid,Gas Chromatographies,Gas-Liquid Chromatographies,Gas-Liquid Chromatography
D004126 Dimethylformamide A formamide in which the amino hydrogens are replaced by methyl groups. N,N-Dimethylformamide,N,N Dimethylformamide
D005260 Female Females
D006207 Half-Life The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. Halflife,Half Life,Half-Lifes,Halflifes
D000280 Administration, Inhalation The administration of drugs by the respiratory route. It includes insufflation into the respiratory tract. Drug Administration, Inhalation,Drug Administration, Respiratory,Drug Aerosol Therapy,Inhalation Drug Administration,Inhalation of Drugs,Respiratory Drug Administration,Aerosol Drug Therapy,Aerosol Therapy, Drug,Drug Therapy, Aerosol,Inhalation Administration,Administration, Inhalation Drug,Administration, Respiratory Drug,Therapy, Aerosol Drug,Therapy, Drug Aerosol
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001273 Atmosphere Exposure Chambers Experimental devices used in inhalation studies in which a person or animal is either partially or completely immersed in a chemically controlled atmosphere. Atmosphere Exposure Chamber,Chamber, Atmosphere Exposure,Chambers, Atmosphere Exposure,Exposure Chamber, Atmosphere,Exposure Chambers, Atmosphere
D012737 Sex Factors Maleness or femaleness as a constituent element or influence contributing to the production of a result. It may be applicable to the cause or effect of a circumstance. It is used with human or animal concepts but should be differentiated from SEX CHARACTERISTICS, anatomical or physiological manifestations of sex, and from SEX DISTRIBUTION, the number of males and females in given circumstances. Factor, Sex,Factors, Sex,Sex Factor

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