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Effect of repeated and prolonged exposure to low concentrations of Low Molecular Weight chemicals on local lymph node responses

Effect van herhaalde en langdurige blootstelling aan lage concentratie van laag moleculaire verbindingen op de lokale lymfklier reacties

Synopsis

The results of the local lymph node assay are not for all compounds useful as starting point for a quantitative risk assessment. This study describes the effects after repeated exposure of the skin to a concentration of a sensitizer below the threshold used in the local lymph node assay. Positive reactions were induced by three of the five investigated compounds (formaldehyde, 2-chloro-N-acetamide, quartenium-15) after long term exposure of the skin to concentrations below the threshold. For two other compounds (paraformaldehyde, hexamethylenetetramine) only a minor increase was observed when the response was compared to the short term exposure schedule. Compounds contacting the skin may induce allergic responses at dosages which do not induce responses in commonly used standard test assays. The local lymph node assay, which is now commonly used for the determination of sensitizing potency of chemicals, uses a threshold above which a compound is considered a contact sensitizer. Tests with doses below this threshold do not result in positive responses in this standard assay. However, there are compounds which induce sensitization after prolonged exposure of the skin to low doses. In order to develop an improved categorization than "yes/no" sensitizer, the question was raised whether the threshold used in the local lymph node assay could be used for the risk assessment of allergenic compounds similar to other test systems. This risk assessment might then result in the determination of safe exposure levels.
 

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