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The aim of the present study is to investigate the "chronotoxicity"of seven metal compounds (Hg, Pb, Ni, Cr, Cu, Zn, or Fe) by assessing how their toxicity varies with circadian periodicity. Male ICR mice were injected with each metal compound intraperitoneally at 6 different time points over the course of a day (zeitgeber time [ZT]: ZT2, ZT6, ZT10, ZT14, ZT18 and ZT22). Mortality was then monitored until 14 days after the injection. Our investigation demonstrated that mice were tolerant against Ni toxicity during dark phase, on the other hand, they were tolerant against Cr toxicity during light phase. The chronotoxicity of Hg and Pb seemed to be biphasic. Further, mice were susceptible to toxicities against Cu and Zn in the time zone during which light and dark were reversed. Interestingly, no significant differences were observed for Fe exposure at any time of the day. Our results propose that the chronotoxicology may provide valuable information regarding the importance of injection timing for not only toxicity evaluation tests but also the reproducibility of animal experiments. Furthermore, our data suggests that chronotoxicology may be an important consideration when evaluating the quality of risk assessments for night shift workers who may be exposed to toxic substances at various times of the day. [ABSTRACT FROM AUTHOR]

Nano-sized titanium dioxide particles (TiO2) are widely used in cosmetics, sunscreens and food additives. We previously reported that topical application of non-coated rutile type TiO2 did not exhibit a promoting effect on ultraviolet B-initiated skin carcinogenesis in rats, and that this was likely due to lack of penetration of TiO2 into the epidermis. In the present study, we examined the promoting effect of silicone coated TiO2 (sTiO2) suspended in silicone oil and non-coated TiO2 (ncTiO2) suspended in Pentalan 408 on a two-stage skin chemical carcinogenesis model: sTiO2 suspended in silicon oil forms smaller particles than ncTiO2 suspended in Pentalan because of the smaller sizes of aggregates formed. The model used skin carcinogenesis-sensitive human c-Ha-ras proto-oncogene transgenic mice (rasH2) and rats (Hras128) and their wild-type counterparts and CD-1 mice to test the effects of topical application of TiO2. Animals were initially treated with a single dose of 7,12-dimethylbenz[a]anthracene (DMBA) and then with 0, 10, or 20 mg sTiO2 (mice) or 0, 50, or 100 mg ncTiO2 (rats). The incidence and multiplicity of skin tumors (squamous cell papilloma and carcinoma) did not increase over DMBA alone controls in skin carcinogenesis-sensitive mice or rats or wild-type animals. Analysis of rat skin indicated that sTiO2 and ncTiO2 did not penetrate though either healthy or damaged skin. Furthermore sTiO2 did not penetrate an in vitro human epidermis model. Our results indicate that treatment with sTiO2 or ncTiO2 did not promote skin carcinogenesis in mice or rats, probably due to lack of penetration through the epidermis. [ABSTRACT FROM AUTHOR]