| Biotransformation and Toxicokinetics of the Insect Repellent IR3535® in Male and Female Human Subjects after Dermal Exposure. | |
| | |
MedLine Citation:
|
PMID: 23402938 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
The absorption and excretion of the insect repellent IR3535(®) was studied in human subjects (five males and five females) after dermal application of approx. 3 grams of a formulation containing 20% IR3535(®), i.e. the total amount of IR3535(®) applied were between 1.94-3.4mmol/person (418 - 731mg/person). Blood and urinary concentrations of IR3535(®) and its only metabolite, IR3535(®)-free acid, were determined over time. In plasma, concentrations of the parent compound IR3535(®) were at or below the limit of quantification (0.037μmol/L). IR3535(®)-free acid peaked in plasma samples 2-6hours after dermal application. C(max) mean values were 5.7μmol/L in males, 3.0 μmol/L in females and 4.2μmol/L in all volunteers. Mean AUC values were 41.6, 24.5 and 33.9μmol x L(-1)x h in males, females and all subjects, respectively. In urine samples from all human subjects, both IR3535(®) and IR3535(®)-free acid were detectable, however, only very small amounts of IR3535(®) were found. Concentrations of IR3535(®)-free acid were several thousand-fold higher than the parent compound and peaked at the first two sampling points (4 h and 8 h after dermal application). Overall, IR3535(®) and IR3535(®)-free acid excreted with urine over 48h representing 13.3±3.05% of the dose applied. Since IR3535(®) is rapidly and extensively metabolized, and IR3535(®)-free acid has a low molecular weight and high water solubility, it is expected that urinary excretion of IR3535(®)-free acid and IR3535(®) represents the total extent of absorption of IR3535(®) in humans. Based on the results of this study, the skin penetration rate of IR3535(®) is 13.3% in humans after dermal application. |
| | |
Authors:
|
Thomas H Broschard; Anja M Bohlmann; Stefan Konietzny; Ute M D Schauer; Wolfgang Dekant |
Related Documents
:
|
15351028 - Meropenem decreases serum level of valproic acid. 23250808 - Evaluation of percutaneous absorption of esculetin: effect of chemical enhancers. 23537878 - Culture condition-dependent metabolite profiling of aspergillus fumigatus with antifun... 16332258 - Unilateral anterior uveitis complicating zoledronic acid therapy in breast cancer. 11745758 - A study of amorphous molecular dispersions of indomethacin and its sodium salt. 21875708 - Hierarchically structured meso-macroporous aluminosilicates with high tetrahedral alumi... |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2013-2-9 |
Journal Detail:
|
Title: Toxicology letters Volume: - ISSN: 1879-3169 ISO Abbreviation: Toxicol. Lett. Publication Date: 2013 Feb |
Date Detail:
|
Created Date: 2013-2-13 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 7709027 Medline TA: Toxicol Lett Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
|
Copyright © 2013. Published by Elsevier Ireland Ltd. |
Affiliation:
|
Non-Clinical Safety, Merck Serono, Merck KGaA, 64271 Darmstadt, Germany. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: In silico prediction of spleen tyrosine kinase inhibitors using machine learning approaches and an o...
Next Document: The effects of aflatoxin B1 on transporters and steroid metabolising enzymes in JEG-3 cells.