Annals of Occupational Hygiene Advance Access originally published online on August 7, 2008
Annals of Occupational Hygiene 2008 52(8):747-756; doi:10.1093/annhyg/men051
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Comparison of Indices Proposed as Criteria for Assigning Skin Notation
1 Institute for Work and Health, University of Lausanne, Bugnon 19, Lausanne 1005, Switzerland
2 Institute for Work and Health, University of Geneva, Bugnon 19, Lausanne 1005, Switzerland
* Author to whom correspondence should be addressed. Tel: +41 (0)21 314 74 21; fax: +41 (0)21 31 47 20; e-mail: pierre-olivier.droz{at}hospvd.ch
Objectives: Skin notations are used as a hazard identification tool to flag chemicals associated with a potential risk related to transdermal penetration. The transparency and rigorousness of the skin notation assignment process have recently been questioned. We compared different approaches proposed as criteria for these notations as a starting point for improving and systematizing current practice.
Methods: In this study, skin notations, dermal acute lethal dose 50 in mammals (LD50s) and two dermal risk indices derived from previously published work were compared using the lists of Swiss maximum allowable concentrations (MACs) and threshold limit values (TLVs) from the American Conference of Governmental Industrial Hygienists (ACGIH). The indices were both based on quantitative structure–activity relationship (QSAR) estimation of transdermal fluxes. One index compared the cumulative dose received through skin given specific exposure surface and duration to that received through lungs following inhalation 8 h at the MAC or TLV. The other index estimated the blood level increase caused by adding skin exposure to the inhalation route at kinetic steady state. Dermal-to-other route ratios of LD50 were calculated as secondary indices of dermal penetrability.
Results: The working data set included 364 substances. Depending on the subdataset, agreement between the Swiss and ACGIH skin notations varied between 82 and 87%. Chemicals with a skin notation were more likely to have higher dermal risk indices and lower dermal LD50 than chemicals without a notation (probabilities between 60 and 70%). The risk indices, based on cumulative dose and kinetic steady state, respectively, appeared proportional up to a constant independent of chemical-specific properties. They agreed well with dermal LD50s (Spearman correlation coefficients –0.42 to –0.43). Dermal-to-other routes LD50 ratios were moderately associated with QSAR-based transdermal fluxes (Spearman correlation coefficients –0.2 to –0.3).
Conclusions: The plausible but variable relationship between current skin notations and the different approaches tested confirm the need to improve current skin notations. QSAR-based risk indices and dermal toxicity data might be successfully integrated in a systematic alternative to current skin notations for detecting chemicals associated with potential dermal risk in the workplace.
Keywords: percutaneous absorption • QSAR • risk analysis • skin notation
Received April 9, 2008; in final form June 27, 2008