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Update on dermal toxicity tests

Charles Miller rellim at tulane.edu
Thu Feb 1 12:29:50 EST 2001

Below is the abstract from a "Forum" paper on dermal toxicity and risk
assessment. New recommendations include the use of the local lymph node
assay and human testing to predict dermal reactions to chemicals. The paper
appears in the latest issue of Toxicological Sciences.

See http://toxsci.oupjournals.org/cgi/content/abstract/59/2/198 for more

Skin Sensitization Testing in Potency and Risk Assessment
I. Kimbera,1, D. A. Basketterb, K. Bertholdc, M. Butlerd, J.-L. Garriguee,
L. Leab, C. Newsomef, R. Roggebandg, W. Steilingh, G. Stroppi, S. Watermanj
and C. Wiemannk 

a Zeneca Central Toxicology Laboratory, Alderley Park, Macclesfield,
Cheshire SK10 4TJ, United Kingdom; b SEAC Toxicology Unit, Unilever
Research, Colworth, Beds MK44 1LQ, United Kingdom; c Asta Medica,
Kantstrasse 2, D-33790, Halle-Kuensebeck, Germany; d ECETOC, Avenue E Van
Nieuwenhuyse 4, B-1160 Brussels, Belgium; e L'Oreal Recherche, 1 Avenue
Eugene Schueller, F-93601 Aulnay-sous-Bois, France; f Union Carbide Benelux
n.v., Noorderlaan 147, B-2030, Antwerp, Belgium; g Procter and Gamble,
Temselaan 100, B-1853 Strombeek-Bever, Belgium; h Henkel KGaA, Henkelstrasse
67, D-40191, Duesseldorf, Germany; i Bayer AG, Friedrich Ebert Strasse
217­333, D-42096 Wuppertal, Germany; j Exxon Biomedical Sciences Inc.,
Mettlers Road CN 2350, East Millstone, New Jersey 08875­2350; and k BASF
Aktiengessellschaft, D-67056 Ludwigshafen, Germany

The purpose of this article is to review, and make recommendations for, the
use of relevant skin sensitization test methods, for the purposes of
determination of relative potency and the threshold dose necessary for the
induction of skin sensitization, and for risk assessment. In addressing the
first area, the utility of three guinea pig tests (the guinea pig
maximization test, the occluded patch test, and the open epicutaneous test)
of the local lymph node assay (LLNA) and of human volunteer testing for the
assessment of relative potency and identification of thresholds for
sensitization were considered. The following conclusions were drawn. (1)
Although attempts have been made to modify the guinea pig maximization test
for the purposes of deriving dose-response relationships, this method is
usually unsuitable for determination of relative sensitizing potency. (2)
Guinea pig methods that do not require the use of adjuvant and which employ
a relevant route of exposure (the occluded patch test and the open
epicutaneous test) are more appropriate for the assessment of relative
skin-sensitizing potency. (3) The LLNA is suitable for the determination of
relative skin sensitizing potency, and the adaptation of this method for
derivation of comparative criteria such as EC3 values (the estimated
concentration of test chemical required to induce a stimulation index of 3
in the LLNA) provides an effective and quantitative basis for such
measurements. (4) For all the methods identified above, potency is assessed
relative to other chemical allergens of known skin sensitizing potential.
The estimation of likely threshold concentrations is dependent upon the
availability of suitable benchmark chemicals of known potency for human
sensitization. (5) Human testing (and specifically, the Human Repeat Insult
Patch Test) can provide information of value in confirming the absence of
skin sensitizing activity of formulations and products under specific
conditions of use and exposure. Based on the above, the following
recommendations are made. (1) If results are already available from suitable
guinea pig tests, then judicious interpretation of the data may provide
information of value in assessing relative skin sensitizing potency. This
option should be explored before other analyses are conducted. (2) The LLNA
is the recommended method for new assessments of relative potency, and/or
for the investigation of the influence of vehicle or formulation on skin
sensitizing potency. (3) Whenever available, human skin sensitization data
should be incorporated into an assessment of relative potency. With respect
to risk assessment, the conclusion drawn is that all the available data on
skin-sensitizing activity in animals and man should be integrated into the
risk-assessment process. Appropriate interpretation of existing data from
suitable guinea pig studies can provide valuable information with respect to
potency, as the first step in the development of a risk assessment. However,
for de novo investigations, the LLNA is the method favored for providing
quantitative estimations of skin-sensitizing potency that are best suited to
the risk assessment process. Finally, human testing is of value in the risk
assessment process, but is performed only for the purposes of confirming
product safety. 

Key Words: skin sensitization; sensitization potency; risk assessment;
guinea pig tests; local lymph node assay; human sensitization.


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