Validity and ethics of the human 4-h patch test as an alternative method to assess acute skin irritation potential.

For more than 50 years, the Draize rabbit skin irritation test has reigned supreme as the regulatory method of choice for the identification of skin irritant chemicals. To date no in vitro alternative test has been validated as an adequate replacement. However, one potential option, to test the endpoint of concern (skin irritation) in the species of concern (man) has been overlooked. The advent of predictive in vitro tools for the identification of substances corrosive to the skin has opened up the practical possibility of carrying out safe and ethical studies on small panels of humans. The human 4-h patch test has been developed to meet the needs of identifying chemical skin irritation potential, providing data which is inherently superior to that given by a surrogate model, such as the rabbit. This paper reviews in detail the present state of the human 4-h patch test, highlighting its advantages and noting its utility as the 'gold standard' on which to build future in vitro models.