Inhalation toxicity of 316L stainless steel powder in relation to bioaccessibility.

The Globally Harmonized System for Classification and Labelling of Chemicals (GHS) considers metallic alloys, such as nickel (Ni)-containing stainless steel (SS), as mixtures of substances, without considering that alloys behave differently compared to their constituent metals. This study presents an approach using metal release, explained by surface compositional data, for the prediction of inhalation toxicity of SS AISI 316L. The release of Ni into synthetic biological fluids is >1000-fold lower from the SS powder than from Ni metal, due to the chromium(III)-rich surface oxide of SS. Thus, it was hypothesized that the inhalation toxicity of SS is significantly lower than what could be predicted based on Ni metal content. A 28-day inhalation study with rats exposed to SS 316L powder (<4 µm, mass median aerodynamic diameter 2.5-3.0 µm) at concentrations up to 1.0 mg/L showed accumulation of metal particles in the lung lobes, but no signs of inflammation, although Ni metal caused lung toxicity in a similar published study at significantly lower concentrations. It was concluded that the bioaccessible (released) fraction, rather than the elemental nominal composition, predicts the toxicity of SS powder. The study provides a basis for an approach for future validation, standardization and risk assessment of metal alloys.

Effects of fumonisin B(1) on the expression of cytokines and chemokines in human dendritic cells.

Fumonisin B(1) (FB(1)) is a mycotoxin produced by the fungus Fusarium verticillioides, which commonly infects corn and other crops across the world. Exposure to FB(1) is known to have toxic and carcinogenic effects in animals, and to express toxicity in cells. In this study, we investigated mechanisms whereby FB(1) may induce immunotoxic effects in human dendritic cells (DC) differentiated from human peripheral blood mononuclear cells. mRNA and protein levels of a number of cytokines and chemokines were analyzed in DC, after exposure to 100 microM FB(1), 10 ng/ml LPS, or a combination of 100 microM FB(1) and 10 ng/ml LPS for 6h or 24h. Exposure to FB(1) resulted in an increase in the expression of IFNgamma and CXCL9. Moreover, FB(1) inhibited the LPS-induced expression of IL-6, IL-1beta, CCL3 and CCL5. The other cytokines studied (TNFalpha, IL-12, IL-18 and IL-23) were not affected by FB(1) in DC. The results of this study indicate that FB(1) has an impact on the expression of cytokines and chemokines in human DC, and in addition to its other toxic effects, FB(1) may also be potentially immunotoxic to humans.

A review of the toxic effects and mechanisms of action of fumonisin B1.

Fumonisin B(1) (FB(1)) is a mycotoxin produced by the fungus Fusarium verticillioides, which commonly infects corn and other agricultural products. Fusarium species can also be found in moisture-damaged buildings, and, therefore, exposure of humans to Fusarium mycotoxins including FB(1) may take place. FB(1) bears a clear structural similarity to the cellular sphingolipids, and this similarity has been shown to disturb the metabolism of sphingolipids by inhibiting the enzyme ceramide synthase leading to accumulation of sphinganine in cells and tissues. FB(1) is neurotoxic, hepatotoxic, and nephrotoxic in animals, and it has been classified as a possible carcinogen to humans. The cellular mechanisms behind FB(1)-induced toxicity include the induction of oxidative stress, apoptosis, and cytotoxicity, as well as alterations in cytokine expression. The effects of FB(1) on different parameters vary markedly depending on what types of cells are studied or what species they originate from. These aspects are important to consider when evaluating the toxic potential of FB(1).