Exaggerated exposure irritation tests

Patch tests have been useful in detecting differences in the irritation potential of some materials however, in some cases predicted differences were not apparent when the materials are used by consumers. Exaggerated exposure tests have been developed to bridge the gap between responses occurring during product use and patch tests. 

One of the oldest nonpatch irritancy tests still in use is the arm immersion technique (Kooyman and Snyder 1942) in which the relative irritancy of two soap or detergent products is compared. Soap solutions of up to 8 % are prepared in troughs. Temperature is to be maintained at 105°F while subjects immerse one hand and arm to just above the elbow in one test solution and the other arm in a solution containing a second product. The period of exposure varied between 10 and 15 min 3 times each day for 5 days or until observable irritation is produced on both arms. 

Evaluation of skin condition before and after use in the home has also been used to compare the irritation potential of various products. These tests represent skin tolerance studies, as either irritation or allergy could be detected. 

Special emphasis should be placed on statistical design of clinical trials of this type to assure validity of the study, as discussed by Allen (1978). 

Allen AM (1978) Clinical trial design in dermatology Experimental design, part I. Int I Dermatol 17 42-51 Bannan EA (1975) Personal communication. 

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Normally, sufficient data will be available for point 1, but generally will not be of much value for the safety assessment, particularly since data from point 2 are rarely available. However, since the skin irritating effects of a formulation are a complex function of the ingredients,32 the most valuable information is derived from the other five points. Of most note are data from point 5, particularly exaggerated exposure studies where a test product is applied to a defined skin site many times a day and is compared to a marketed product known to have an extensive history of safe use. Valuable information often comes also from more extended consumer use tests, perhaps undertaken in a number of locations to allow for differences in use habits. Ultimately it is not possible to do predictive studies (clinical or in vitro) which will predict the market place perfectly, particularly low level complaint rates — which means that point 7, monitoring feedback from the market, is always of importance. 

In a 90-day repeated dose dermal study, rabbits developed skin irritation at each of three levels tested (14, 27, and 68 mg/kg/day tributyltin fluoride) (Sheldon 1975). Deaths occurred in 7 of 10 rabbits at a level of 68 mg/kg, but surviving animals eventually returned to normal a few days after compound was withdrawn. A level of 14 mg/kg (65 applications) was stated by the authors to be a NOAEL despite local irritation at the application sites. In view of the exaggerated daily contact with the rabbit skin, this value seems reasonable since such high levels of daily exposure would not be the case in humans. However, a detailed report of this study was not available for review. 

These are conducted to gain information on the cumulative irritancy of a product. This type of test is designed to mirror the intended use of the product, but exposure may also be exaggerated, to provide a greater margin of safety in the risk assessment on the product and also to provide information on problems that may be encountered should the product be misused. Some methods are designed to simulate the normal use of products, with controlled exposure. The skin irritation is monitored and comparisons made between the test and control product in the same panellist. The controls are... 

In use tests represent a very valuable tool in the assessment armory. Many personal care products are designed for frequent skin contact, often with very sensitive areas of skin (e.g., the face or underarm). Materials such as face creams and deodorants, etc. must therefore be evaluated for their irritation potential to ensure that they are safe for normal use. A use or exaggerated use test provides data on which a safety assessment can be made. A test material is compared with a control, usually a material of similar formulation that is already marketed, and has an acceptable market history. The frequency of exposure may be exaggerated to maximize the sensitivity of the test. For the duration of the test, panellists are provided with test and control materials and a treatment card to record the daily use of each material. The materials issued at the start of the test are weighed before and after the test, so that the amount of material used can be calculated. 

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