The human use of sunscreens is now a wide-spread practice alleviating the damage incurred from over-exposure to solar radiation. In normal use, sunscreens contain relatively high concentrations of active chemical ingredients which are applied to large areas of skin. This thesis provides a critical review of the implications of current sunscreen use in humans. It is important is to ascertain the clinical significance of any perceived or reported toxicity. For instance, although skin reactions are uncommonly encountered, the reactivity of certain sunscreens necessitated their removal from marketed products. This fact is evidence that a quantity of sunscreen permeates the epidermis sufficient to elicit these effects. Yet skin permeation of sunscreens is commonly regarded as being low and clinically insignificant. However, the diverse range of chemicals used as sunscreens infers that variable skin permeation is likely between substances. On the basis of this review, the weight-of-evidence currently favours the continued use of sunscreens, with benefits exceeding all presently perceivable risks. Yet the lack of published safety profiles of sunscreens provides a basis for further research and scrutiny. A review of sunscreen use in Australia compared the regulatory status of sunscreens in the major markets of Europe, United States, and Japan. On reviewing all sunscreen products listed in Australia, the chemicals actually used were identified. The approved sunscreens comprise a wide range of chemical classes, with the common being ethylhexyl methoxycirmamate (77%), butyl methoxy dibenzoylmethane (46%) and oxybenzone (45%). Australia seemingly allows the use of the greatest number of individual substances, more than twice that of any other region. Fortunately, only a small number of approved sunscreens are actually used in Australian products. A critical revision of the Australian list of approved sunscreens would be prudent and should result in the removal of those substances which are not in contemporary use, have less than benchmark efficacy, or are without complete or adequate safety profiles. The list has since been updated and remains under review. Analytical methods were developed for the quantification and qualification of a wide variety of sunscreen chemicals in numerous matrices. These methods included high performance liquid chromatography with ultraviolet absorption detection, mass spectroscopy, and ultraviolet spectroscopy. A suitable in vitro method was investigated to assess the skin permeation of sunscreens from simple solutions and commercial products. Although in vivo skin permeation studies provide gold-standard data, they are expensive to perform and time consuming. Thus a suitable in vitro static (Franz-type) diffusion apparatus was used to expose excised human skin to sunscreens. Other synthetic films, semi-permeable, and porous membranes were also examined for suitability in this in vitro system. The "release" of sunscreens from vehicles was examined in an attempt to establish a method to predict solute-retention by different formulations. Commercial formulations were applied to human skin and amounts were measured within the epidermis and in a receptor solution bathing the inner surface of the excised tissue. Significant amounts of sunscreens were measured in the epidermis and some sunscreen was detected in the receptor solution. The physico-chemical differences between those sunscreens with high and limited percutaneous penetration appear related to lipophilicity. The highly lipophilic substances remain within the epidermis, however, greater permeation is observed for oxybenzone (which is less lipophilic). Further evidence of skin permeation in clinical studies was procured. A commercial formulation containing commonly used sunscreens was applied to the skin of human volunteers. The subjects collected their urine output for the following two days. On analysis of the urine for sunscreens, oxybenzone and its metabolites were measured. The urinary excretion as a reflection of the amount absorbed was variable between individuals, with the small heterogeneous group of subjects (male and female) with innate differences in skin permeability being the predominant cause. A clinical cutaneous microdialysis method was used in an attempt to recover sunscreens in dermis immediately below the site of application. As sunscreens are poorly water soluble and extensively associated with proteins in solution, the ability to "recover" these solutes in microdialysate is problematic. So limited skin absorption of sunscreens combined with low dialysate recovery allowed detection of only very minor amounts of oxybenzone by cutaneous microdialysis. The use of in vitro toxicity systems are a necessary alternative to animal testing. Although sunscreens have little to no irritancy to human skin, the relative cellular toxicity of sunscreens is rarely reported. To gain an insight into the potential cellular toxicity of sunscreens, selected substances were dosed to human epidermal keratinocytes in proliferating cultures. The common sunscreens had varying degrees of effects on cell proliferation, with altered morphology and cell death occurring at different levels for each substance. Altered cell proliferation is a non-specific end-point but it was demonstrated that sunscreens have measurable effects on human skin cells in culture. The application of this data is limited to clinical scenarios however, the methodology is a step towards further studies aimed at evaluating hypothesised UV-induced cellular toxicity by sunscreens, degradation products and metabolites. In conclusion, this thesis presents evidence that sunscreens are absorbed into and through human skin in vitro and in vivo to varying extents. The chemical properties of most sunscreens result in low skin permeation, but significant systemic distribution occurs for some substances. The toxicological implications of this skin permeation are unlikely to be clinically significant, but so far little attention has been placed on elucidating minor toxicological effects in humans. There is wide scope for further research on sunscreen pharmacology and toxicology, including aspects of photobiological effects, systemic distribution in humans, control of delivery to the epidermis and formulation product design.