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Based on the current weight of evidence of all available data, the risk for humans from the use of nano-structured titanium dioxide (TiO(2)) or zinc oxide (ZnO) currently used in cosmetic preparations or sunscreens is considered negligible. There is a large body of information that when viewed in its entirety is considered as sufficient to demonstrate that these nano-structured ultraviolet (UV) filters, irrespective of various treatments (coatings) or crystalline structure, can be regarded as safe for use at concentrations up to 25% in cosmetic products to protect the skin from harmful effects of solar UV radiation. "Nano" TiO(2) and ZnO formulated in topically applied sunscreen products exist as aggregates of primary particles ranging from 30-150 nm in size. These aggregates are bonded such that the force of sunscreen product application onto the skin would have no impact on their structure or result in the release of primary particles. Multiple studies have shown that under exaggerated test conditions neither nano-structured TiO(2) nor ZnO penetrates beyond the stratum corneum of skin. Further, the distribution and persistence of these nano-structured metal oxides is the same compared to larger pigment-grade (i.e., >100 nm) particles, demonstrating equivalence in the recognition and elimination of such material from the body. Finally, the in vitro genotoxic and photogenotoxic profiles of these nano-structured metal oxides are of no consequence to human health. Whereas the most logical, straightforward conclusion based on data from internationally-recognized guideline studies and current 20+ year history of human use is that nano-structured TiO(2) and ZnO are safe, there will continue to be questions as "nano" conjures images of technology gone awry. Despite this rather sober view, the public health benefits of sunscreens containing nano TiO(2) and/or ZnO outweigh human safety concerns for these UV filters.

The use of sunscreen products has been advocated by many health care practitioners as a means to reduce skin damage produced by ultraviolet radiation (UVR) from sunlight. There is a need to better understand the efficacy and safety of sunscreen products given this ongoing campaign encouraging their use. The approach used to establish sunscreen efficacy, sun protection factor (SPF), is a useful assessment of primarily UVB (290-320 nm) filters. The SPF test, however, does not adequately assess the complete photoprotective profile of sunscreens specifically against long wavelength UVAI (340-400 nm). Moreover, to date, there is no singular, agreed upon method for evaluating UVA efficacy despite the immediate and seemingly urgent consumer need to develop sunscreen products that provide broad-spectrum UVB and UVA photoprotection. With regard to the safety of UVB and UVA filters, the current list of commonly used organic and inorganic sunscreens has favorable toxicological profiles based on acute, subchronic and chronic animal or human studies. Further, in most studies, sunscreens have been shown to prevent the damaging effects of UVR exposure. Thus, based on this review of currently available data, it is concluded that sunscreen ingredients or products do not pose a human health concern. Further, the regular use of appropriate broad-spectrum sunscreen products could have a significant and favorable impact on public health as part of an overall strategy to reduce UVR exposure.

In vivo microdialysis was used to determine whether the 3,4‐methylenedioxymethamphetamine (MDMA)‐induced release of serotonin (5‐HT) in vivo involves a carrier‐mediated process and to investigate further the state‐dependent interaction between 5‐HT and dopamine. MDMA produced a dose‐dependent increase in the extracellular concentration of 5‐HT in the striatum and prefrontal cortex that was attenuated by treatment with fluoxetine but not by tetrodotoxin. Suppression by fluoxetine of the MDMA‐induced release of 5‐HT was accompanied by a suppression of the MDMA‐induced release of dopamine. Administration of MDMA to rats treated with carbidopa and l‐5‐hydroxytryptophan resulted in a synergistic elevation of the extracellular concentration of 5‐HT that was much greater than that produced by either treatment alone. The MDMA‐induced release of dopamine by MDMA also was potentiated in 5‐hydroxytryptophan‐treated rats. These data are consistent with the view that MDMA increases the extracellular concentration of 5‐HT by facilitating carrier‐mediated 5‐HT release, which can be enhanced greatly under conditions in which 5‐HT synthesis is stimulated. Moreover, these data are supportive of a state‐dependent, stimulatory role of 5‐HT in the regulation of dopamine release.

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The factors that control the reactivities of aryl radicals toward hydrogen-atom donors were studied by using a dual-cell Fourier-transform ion cyclotron resonance mass spectrometer (FT – ICR). Hydrogen-atom abstraction reaction efficiencies for two substrates, cyclohexane and isopropanol, were measured for twenty-three structurally different, positively-charged aryl radicals, which included dehydrobenzenes, dehydronaphthalenes, dehydropyridines, and dehydro(iso)quinolines. A logarithmic correlation was found between the hydrogen-atom abstraction reaction efficiencies and the (calculated) vertical electron affinities (EA) of the aryl radicals. Transition state energies calculated for three of the aryl radicals with isopropanol were found to correlate linearly with their (calculated) EAs. No correlation was found between the hydrogen-atom abstraction reaction efficiencies and the (calculated) enthalpy changes for the reactions. Measurement of the reaction efficiencies for the reactions of several different hydrogen-atom donors with a few selected aryl radicals revealed a logarithmic correlation between the hydrogen-atom abstraction reaction efficiencies and the vertical ionization energies (IE) of the hydrogen-atom donors, but not the lowest homolytic X – H (X = heavy atom) bond dissociation energies of the hydrogen-atom donors. Examination of the hydrogen-atom abstraction reactions of twenty-nine different aryl radicals and eighteen different hydrogen-atom donors showed that the reaction efficiency increases (logarithmically) as the difference between the IE of the hydrogen-atom donor and the EA of the aryl radical decreases. This dependence is likely to result from the increasing polarization, and concomitant stabilization, of the transition state as the energy difference between the neutral and ionic reactants decreases. Thus, the hydrogen-atom abstraction reaction efficiency for an aryl radical can be “tuned” by structural changes that influence either the vertical EA of the aryl radical or the vertical IE of the hydrogen atom donor.

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