Refinement of the acute inhalation limit test for inert, nano-sized dusts by an dosimetry-based evaluation: case study for the dissolution of a regulatory dilemma.

This case study aims to describe the dilemma faced when exposing rats to very high concentrations of fine, pulverulent materials for acute inhalation studies and to address the regulatory question of whether the effects seen here are relevant to humans and the subject of classification according to the Globally Harmonized System of Classification and Labeling of Chemicals (GHS). Many powders match the definition of nanomaterials in the EU; therefore, information on acute inhalation testing of powders up to the GHS cutoff of 5 mg/L is required. However, testing rats at such a high aerosol concentration can cause physical obstruction of the airways and even mortality by suffocation.

Possibilities to group nanomaterials across different substances - A case study on organic pigments.

Grouping concepts to reduce the testing of NFs have been developed for regulatory purposes for different forms of the same substance. Here we explore possibilities to group nanomaterials across different substances for non-regulatory applications, using the example of 16 organic pigments from six chemical classes. Organic pigments are particles consisting of low-molar-mass organic molecules, and rank by tonnage among the most important substances manufactured in nanoform (NF).

Classes of organic pigments meet tentative PSLT criteria and lack toxicity in short-term inhalation studies.

Here, we present a non-animal testing battery to identify PSLT (poorly soluble, low toxicity) substances based on their solubility in phagolysosomal lung fluid simulant, surface reactivity and effects on alveolar macrophages in vitro. This is exemplified by eleven organic pigments belonging to five chemical classes that cover a significant share of the European market. Three of the pigments were tested as both, nanoform and non-nanoform.

Indicators for lack of systemic availability of organic pigments.

Experimental data of all 143 organic pigments registered with the European Chemicals Agency, of which 88 were listed in a nanomaterial inventory, was retrieved from the registered substance fact sheets. Availability of the data was 93% for solubility, 82% for bacterial mutagenicity, 79% for acute oral toxicity, 75% for irritation, 59% for skin sensitisation, 36% for repeated dose toxicity and 34% for each clastogenicity and mutagenicity in mammalian cells and 23% for toxicity to reproduction. Pigments mostly had a water and octanol solubility of significantly below 0.

Pleiotropic role of Rac in mast cell activation revealed by a cell permeable Bordetella dermonecrotic fusion toxin.

To activate the GTPase Rac in rat basophilic leukemia (RBL) cells and mouse bone marrow-derived mast cells (BMMC) a TAT fusion toxin of Bordetella dermonecrotic toxin (DNT-TAT) was constructed. The fusion toxin activated Rac1 and RhoA in vitro but only Rac in RBL cells and BMMC. DNT-TAT caused an increase in inositol phosphate formation, calcium mobilization, ERK activation and degranulation of mast cells.