Studies on acute dermal toxicity and dermal absorption of a nanoform zinc oxide (ZnO; NM-111) in rats

In two studies, the dermal toxicity (limit test following OECD TG 402) and toxicokinetics (with [⁶⁵Zn]-tagged ZnO following OECD TG 427) of a nanostructured ZnO particle were characterized. The overall aim was to assess the risk of its systemic availability. Wistar rats were dermally treated once with 2000 mg ZnO/kg b.w. (limit test). - Male rats were treated topically with 2 mg/cm^{2 65}ZnO for 6 h. Necropsy was done after the end of the exposure period (6 h) and after 24 and 72 h to investigate dermal absorption of ⁶⁵ZnO. ZnO showed no clinical signs of toxicity in the limit test. - ⁶⁵ZnO was not significantly absorbed following deposition: In the group means, 62-76 % of the dose applied were recovered in the not absorbed fraction. The amount of ⁶⁵ZnO in the stratum corneum was found to be approx. 15 %, 8 % and 4.6 % after 6, 24 and 72 h, respectively. The ⁶⁵ZnO content in the remaining skin at the application site (viable skin + remaining stratum corneum) accounted for approx. 10 %, 16 % and 16 % after 6, 24 and 72 h (total on/in the skin 25 %, 24 % and 20.6 % after 6, 24 and 72 h). No relevant radioactivity was found in faeces, urine, cage wash, organ or tissue samples. The acute dermal limit test with ZnO resulted in 'Unclassified' (globally harmonized system). - Radioactivity, representative of ⁶⁵ZnO, was not detected systemically after dermal application. Overall, the results indicate that ⁶⁵ZnO was not absorbed with subsequent translocation beyond the skin into the blood compartment.