Percutaneous embryotoxicity testing of chemicals

Abstract

The skin is an important interface between humans and the environment as well as animals and the environment. The skin is also an important portal of entry for various chemicals. The most common exposure of humans or animals to foreign chemicals of all types is by exposure through accidental or intentional contact of the chemical with the skin¹. The incidence of occupational skin disease as determined from workmen’s compensation statistics has ranged from 25 to 80% of all occupational diseases². It is reasonable to expect that at least trace amounts of the causative toxic agents are absorbed internally from the affected skin. Many chemicals have been found to be absorbed percutaneously in humans and animals^3–17. The incidence where significant amounts of toxic chemicals are absorbed internally from the skin of pregnant women is not known. Factors that determine the rate of percutaneous absorption of chemicals include: concentration and rate of application, pH, water/lipid solubility, solvents/vehicles, chemical structure, molecular size, state of ionization, temperature, number of hair follicles, thickness, state of hydration and other changes to the stratum corneum¹⁸. The mechanisms of various body defences against toxic chemicals are not well understood. Likewise, the specific body defence differences that exist in the major portals of entry (skin, oral and inhalation) are not well understood. It is for these reasons that a good toxicological test design should include exposure of experimental animals by routes where humans are most apt to be exposed.