Pharmacokinetics and bioavailability of diisopropanolamine (DIPA) in rats following intravenous or dermal application

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• 作者：S.A. Saghir ; S.W. Frantz ; M.W. Spence ; R.J. Nolan ; E.R. Lowe ; D.L. Rick ; M.J. Bartels
• 关键词：Diisopropanolamine ; DIPA ; Phamacokinetics of DIPA in rats ; Fate of DIPA after dermal application to rats ; Fate of DIPA after intravenous administration to rats ; Implication to human exposure
• 刊名：Food and Chemical Toxicology
• 出版年：2007
• 期刊代码：20_02786915
• 类别：pha
• 出版时间：October 2007
• 卷：45
• 期：10
• 页码：2047-2056
• 文件大小：199 K

摘要

This study was conducted to determine the relative dermal bioavailability (absorption), distribution, metabolism, and excretion (ADME) of diisopropanolamine (DIPA), an alcohol amine used in a number of industrial and personal care products. Groups of 4 female Fischer 344 rats received either a single bolus i.v. dose of 19.0 mg/kg p>14p>C-DIPA in water or a dermal application of 19.5 mg/kg p>14p>C-DIPA in acetone to an area of 1 cmp>2p> on the back and covered with a bandage. Time-course blood and excreta were collected and radioactivity determined. Urine was analyzed for DIPA and monoisopropanolamine (MIPA). Following i.v. administration, DIPA was rapidly cleared from the plasma and excreted into urine in a biexponential manner (t_1/2α, 0.4 h; t_1/2β, 2.9 h). The levels of radioactivity in plasma dropped below the limit of detection 12 h post-dosing. A total of 97 ± 4%of the dose was actively excreted in urine by kidney, most (p://www.sciencedirect.com/scidirimg/entities/223c.gif" alt="not, vert, similar" border=0>71%) within 6 h of dosing, virtually all as parent compound; renal clearance exceeded the glomerular filtration rate. Following dermal application, p://www.sciencedirect.com/scidirimg/entities/223c.gif" alt="not, vert, similar" border=0>20%of the dose was absorbed in 48 h with the steady-state penetration rate of p://www.sciencedirect.com/scidirimg/entities/223c.gif" alt="not, vert, similar" border=0>0.2%/h. Most (14.4%) of the applied radioactivity was excreted in urine at a relatively constant rate due to the presence of large amount of the p>14p>C-DIPA at the application site. Fecal elimination was <0.2%of the dose. The absorbed DIPA did not accumulate in tissues; only p://www.sciencedirect.com/scidirimg/entities/223c.gif" alt="not, vert, similar" border=0>0.1%of the administered dose was found in liver and kidney. The absolute systemic dermal bioavailability (dose corrected AUC_dermal/AUC_i.v.) of p>14p>C-DIPA was 12%. The ADME of DIPA contrasts that of its diethanol analogue, diethanolamine, which displays a broad spectrum of toxicity in rats and mice. Toxicologically significant concentrations of DIPA are unlikely to be achieved in the systemic circulation and/or tissues as a result of repeated dermal application of products containing DIPA due to slow absorption from the skin, rapid unchanged elimination in urine, and majority of the products contain p://www.sciencedirect.com/scidirimg/entities/2a7d.gif" alt="less-than-or-equals, slant" border=0>1%DIPA.