The number of workplace substances is uncountable, and technical progress enforces the adaptation of substances such as cutting fluids to the new demands. For that reason new substances can hardly be tested in in vivo studies. In vitro models are widely used to test the effects of barrier creams since they are simple, rapid and safe. Since no animal model could perfectly mimic human percutaneous absorption, these tests are particularly recommended as screening procedures for barrier cream candidates. A number of in vivo methods exist whereupon conventional, non-invasive bioengineering methods, along with clinical scoring, provide the most accurate, highly reproducible assessment of the inflammatory response to irritants and allergens. Nevertheless, no general accepted procedure for the evaluation of skin protection products exists. It is essential that all the products applied to the skin (protective creams inclusive) should be clinically tested in order to verify their propensity for causing cutaneous reactions. Safety testing is a stepwise approach, comprising various in vitro and in vivo test models. The nature of the plausible biological or even toxic reactions that might occur and the types of tests designed to determine the safety of the topical formulations in men are described in this chapter.