Document Detail


New in vitro dermal absorption database and the prediction of dermal absorption under finite conditions for risk assessment purposes.
MedLine Citation:
PMID:  20178823     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Most QSARs for dermal absorption predict the permeability coefficient, K(p), of a molecule, which is valid for infinite dose conditions. In practice, dermal exposure mostly occurs under finite dose conditions. Therefore, a simple model to predict finite dose dermal absorption from infinite dose data (K(p) and lag time) and the stratum corneum/water partition coefficient (K(SC,W)) was developed. To test the model, a series of in vitro dermal absorption experiments was performed under both infinite and finite dose conditions using acetic acid, benzoic acid, bis(2-ethylhexyl)phthalate, butoxyethanol, cortisone, decanol, diazinone, 2,4-dichlorophenol, ethacrynic acid, linolenic acid, octylparaben, oleic acid, propylparaben, salicylic acid and testosterone. For six substances, the predicted relative dermal absorption was not statistically different from the measured value. For all other substances, measured absorption was overpredicted by the model, but most of the overpredictions were still below the European default absorption value. In conclusion, our finite dose prediction model provides a useful and cost-effective estimate of dermal absorption, to be used in risk assessment for non-volatile substances dissolved in water at non-irritating concentrations.
Authors:
Harrie E Buist; Johan A van Burgsteden; Andreas P Freidig; Wilfred J M Maas; Johannes J M van de Sandt
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-02-21
Journal Detail:
Title:  Regulatory toxicology and pharmacology : RTP     Volume:  57     ISSN:  1096-0295     ISO Abbreviation:  Regul. Toxicol. Pharmacol.     Publication Date:    2010 Jul-Aug
Date Detail:
Created Date:  2010-06-02     Completed Date:  2010-09-16     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8214983     Medline TA:  Regul Toxicol Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  200-9     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier Inc. All rights reserved.
Affiliation:
Department of Food & Chemical Risk Analysis, TNO Quality of Life, Zeist, The Netherlands. harrie.buist@tno.nl
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MeSH Terms
Descriptor/Qualifier:
Adult
Databases, Factual*
Dose-Response Relationship, Drug
Female
Hormones / chemistry,  pharmacokinetics
Humans
Lipids / chemistry,  pharmacokinetics
Middle Aged
Models, Biological*
Organic Chemicals / chemistry,  pharmacokinetics
Prognosis
Quantitative Structure-Activity Relationship
Risk Assessment
Skin / metabolism*
Skin Absorption / physiology*
Chemical
Reg. No./Substance:
0/Hormones; 0/Lipids; 0/Organic Chemicals

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