Nanotechnology is a rapidly developing field in the 21(st) century, and the commercial use of nanomaterials for novel applications is increasing exponentially. To date, the scientific basis for the cytotoxicity and genotoxicity of most manufactured nanomaterials are not understood. The mechanisms underlying the toxicity of nanomaterials have recently been studied intensively. An important mechanism of nanotoxicity is the generation of reactive oxygen species (ROS). Overproduction of ROS can induce oxidative stress, resulting in cells failing to maintain normal physiological redox-regulated functions. This in turn leads to DNA damage, unregulated cell signaling, change in cell motility, cytotoxicity, apoptosis, and cancer initiation. There are critical determinants that can affect the generation of ROS. These critical determinants, discussed briefly here, include: size, shape, particle surface, surface positive charges, surface-containing groups, particle dissolution, metal ion release from nanometals and nanometal oxides, UV light activation, aggregation, mode of interaction with cells, inflammation, and pH of the medium.

Polycyclic aromatic hydrocarbons (PAHs) are a class of mutagenic and tumorigenic environmental contaminants. Although the mechanisms by which PAHs induce cancer in experimental animals have been extensively studied and the metabolic activation pathways have been determined, the environmental fate of PAHs and the phototoxicity exerted by PAHs, as well as their photoreaction products formed in the environment, have received much less attention. In this review, the formation of oxygenated PAHs, PAH quinones, nitro-PAHs, and halogenated PAHs from photoreaction of environmental PAHs are addressed. Upon light irradiation, PAHs and all PAH photoreaction products can absorb light energy to reach photo-excited states, which react with molecular oxygen, medium, and coexisting chemicals to produce reactive oxygen species (ROS) and other reactive intermediates, such as oxygenated PAHs and free radicals. These intermediates, including ROS, induce lipid peroxidation, and DNA damage including DNA strand breakage, oxidation to 8-oxo-2′-deoxyguanosine, and DNA-adducts. Since these toxicological endpoints are associated with age-related diseases, including cancer, environmental PAHs concomitantly exposed to sunlight may potentially promote human skin damage, leading to ageing and skin cancers. Thus, we suggest that (i) in addition to the widely recognized metabolic pathways, more attention must be paid to photoreaction as an important activation pathway for PAHs, (ii) risk assessment of environmental PAHs should take into consideration the complex photochemical reactions leading to mixtures of products that are also phototoxic; and (iii) the study of structure-toxicity relationships should be expanded to cover the complex photoreactions and extrinsic factors that affect phototoxicity endpoints.

Kava is a traditional beverage of various Pacific Basin countries. Kava has been introduced into the mainstream U.S. market principally as an anti-anxiety preparation. The effects of the long-term consumption of kava have not been documented adequately. Preliminary studies suggest possible serious organ system effects. The potential carcinogenicity of kava and its principal constituents are unknown. As such, kava extract was nominated for the chronic tumorigenicity bioassay conducted by the National Toxicology Program (NTP). At present toxicological evaluation of kava extract is being conducted by the NTP. The present review focuses on the recent findings on kava toxicity and the mechanisms by which kava induces hepatotoxicity.