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    Primer towards an in vitro test for screening irritant potency of compounds

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    Authors
    Vandebriel RJ
    Machielsen A
    Bakker K
    van Loveren H
    Type
    Report
    Language
    en
    
    Metadata
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    Title
    Primer towards an in vitro test for screening irritant potency of compounds
    Translated Title
    Opstap naar een in vitro test voor het screenen van de irriterende potentie van stoffen
    Publiekssamenvatting
    Het vaststellen van de allergene potentie van stoffen wordt in het algemeen uitgevoerd met behulp van de 'Buehler occluded patch test' en de 'guinea pig maximization test', terwijl de auriculaire lymfkliertest gebruikt wordt voor screening. Deze testen hebben veel informatie opgeleverd over de allergene potentie van stoffen. Er is grote vooruitgang geboekt in het ophelderen van de mechanismen van huidsensitizatie, waaronder effecten op de productie van cytokinen en mediatoren alsmede expressie van adhesiemoleculen. Deze kennis zou mogelijk kunnen leiden tot het testen van allergene potentie in vitro. De rationale achter deze manier van testen is een terugdringing van het proefdiergebruik. Een mogelijk bijkomend voordeel van deze testmethode is de mogelijkheid om cellen van humane oorsprong te gebruiken. Er is gesuggereerd dat de irriterende capaciteit van allergenen een additionele risicofactor vormt in zoverre, dat irriterende allergenen sterkere allergenen zouden zijn dan niet-irriterende. In deze studie zijn hiertoe de irriterende potentie van oxazolone, een sterk sensitizerende verbinding, benzocaine, een zwak sensitizerende verbinding en glycerol, een niet-sensitizerende verbinding, onderzocht. Hoewel irriterende potentie werd gedetecteerd, konden we niet discrimineren tussen oxazolone en benzocaine. Te hoge blootstellingsconcentraties zijn hiervoor mogelijk verantwoordelijk. Glycerol kon wel worden onderscheiden van oxazolone en benzocaine.<br>
    Testing for allergenic potency of compounds is often performed using the Buehler occluded patch test and the guinea pig maximization test, while screening is performed using the auricular lymph node assay. Much information on allergenic potency has been obtained from these tests. Considerable progress has been made in unraveling the mechanisms of skin sensitization, including effects on the production of cytokines and mediators, and expression of adhesion molecules. This knowledge may open the way to in vitro testing for allergenic potency. Reduction of animal use is the rationale behind this way of testing. A possible additional advantage of this type of testing is the possibility to use cells from human origin. It has been suggested that irritant capacity of allergens may present an additional risk factor in that irritant allergens may be stronger allergens than non-irritant ones. Therefore, in the present study the irritant potency of oxazolone, a strong sensitizer, benzocaine, a weak sensitizer, and glycerol, a non-sensitizing compound, is investigated. Although we were able to detect irritant potency, we were unsuccessful in discriminating irritant potency between oxazolone and benzocaine. Too high exposure concentrations may be a cause for this result. Glycerol could be discriminated from oxazolone and benzocaine.<br>
    Publisher
    Rijksinstituut voor Volksgezondheid en Milieu RIVM
    Sponsors
    RIVM
    URI
    http://hdl.handle.net/10029/257652
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