Document Detail

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    
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.
Thomas H Broschard; Anja M Bohlmann; Stefan Konietzny; Ute M D Schauer; Wolfgang Dekant
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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.
Non-Clinical Safety, Merck Serono, Merck KGaA, 64271 Darmstadt, Germany.
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