title: Metabolism and disposition of [(14)C]dimethylamine borane in male Harlan Sprague Dawley rats following gavage administration, intravenous administration and dermal application.
abstract: 1. Dimethylamine borane (DMAB) is used as a reducing agent in the manufacturing of a variety of products and in chemical synthesis. National Toxicology Program is evaluating the toxicity of DMAB in rodents following dermal application. The objective of this study was to evaluate the metabolism and disposition of DMAB in male Harlan Sprague Dawley (HSD) rats. 2. Disposition of radioactivity was similar between gavage and intravenous administration of 1.5 mg/kg [(14)C] DMAB, with nearly 84%-89% of the administered radioactivity recovered in urine 24 h post dosing. At 72 h, only 1% or less was recovered in feces, 0.3% as CO2, and 0.5%-1.4% as volatiles and 0.3%-0.4 % in tissues. 3. The absorption of [(14)C]DMAB following dermal application was moderate; percent dose absorbed increased with the dose, with 23%, 32% and 46% of dose absorbed at 0.15, 1.5 and 15 mg/kg, respectively. Urinary and fecal excretion ranged from 18%-37% and 2%-4% of dose, respectively, and 0.1%-0.2% as CO2, and 1%-3% as volatiles. Tissue retention of the radiolabel was low ∼1%, but was higher than following the gavage or intravenous administration. 4. Following co-adminsitration of DMAB and sodium nitrite by gavage, N-nitrosodimethylamine was not detected in blood or urine above the limit of quantitation of the analytical method of 10 ng/mL. 5. Absorption of DMAB in fresh human skin in vitro was ∼41% of the applied dose: the analysis of the receptor fluid shows that the intact DMAB complex can be absorbed through the skin.
authors.affiliation: RTI International, Drug Metabolism and Pharmacokinetics , Research Triangle Park , USA , and.
authors.forename: James M
authors.initials: JM
authors.lastname: Mathews
authors.forename: Scott L
authors.initials: SL
authors.lastname: Watson
authors.forename: Purvi R
authors.initials: PR
authors.lastname: Patel
authors.forename: Sherry R
authors.initials: SR
authors.lastname: Black
authors.forename: Yan
authors.initials: Y
authors.lastname: Hong
authors.forename: Keith E
authors.initials: KE
authors.lastname: Levine
authors.forename: Glenn
authors.initials: G
authors.lastname: Ross
authors.forename: Dori R
authors.initials: DR
authors.lastname: Germolec
authors.forename: Sheetal A
authors.initials: SA
authors.lastname: Thakur
authors.forename: Suramya
authors.initials: S
authors.lastname: Waidyanatha
mesh_terms: D000279:Administration, Cutaneous; D061605:Administration, Intravenous; D000818:Animals; D001880:Boranes / Q000008:administration & dosage* / Q000378:metabolism* / Q000493:pharmacokinetics; D002250:Carbon Radioisotopes / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000652:urine; D004123:Dimethylamines / Q000008:administration & dosage* / Q000378:metabolism* / Q000493:pharmacokinetics; D004128:Dimethylnitrosamine / Q000097:blood / Q000652:urine; D005243:Feces / Q000737:chemistry; D006801:Humans; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012977:Sodium Nitrite / Q000008:administration & dosage
chemical_list: D001880:Boranes; D002250:Carbon Radioisotopes; D004123:Dimethylamines; C034516:dimethylamine; D012977:Sodium Nitrite; D004128:Dimethylnitrosamine