Skin sensitization testing in potency and risk assessment

The purpose of this article is to review, and make recommendations for, the use of relevant skin sensitization test methods, for the purposes of deter mination of relative potency and the threshold dose necessary for the induc tion of skin sensitization, and for risk assessment, In addressing the firs t 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 ha ve been made to modify the guinea pig maximization test for the purposes of deriving dose-response relationships, this method is usually unsuitable fo r determination of relative sensitizing potency. (2) Guinea pig methods tha t do not require the use of adjuvant and which employ a relevant route of e xposure (the occluded patch test and the open epicutaneous test) are more a ppropriate for the assessment of relative skin-sensitizing potency. (3) The LLNA is suitable for the determination of relative skin sensitizing potenc y, 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 q uantitative basis for such measurements, (4) For all the methods identified above, potency is assessed relative to other chemical allergens of known s kin sensitizing potential. The estimation of likely threshold concentration s is dependent upon the availability of suitable benchmark chemicals of kno wn potency for human sensitization. (5) Human testing (and specifically, th e Human Repeat Insult Patch Test) can provide information of value in confi rming the absence of skin sensitizing activity of formulations and products under specific conditions of use and exposure. Based on the above, the fol lowing recommendations are made. (1) If results are already available from suitable guinea pig tests, then judicious interpretation of the data may pr ovide 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, an d/or for the investigation of the influence of vehicle or formulation on sk in sensitizing potency. (3) Whenever available, human skin sensitization da ta should be incorporated into an assessment of relative potency. With resp ect 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 fr om suitable guinea pig studies can provide valuable information with respec t to potency, as the first step in the development of a risk assessment. Ho wever, for de novo investigations, the LLNA is the method favored for provi ding quantitative estimations of skin-sensitizing potency that are best sui ted to the risk assessment process. Finally, human testing is of value in t he risk assessment process, but is performed only for the purposes of confi rming product safety.