Comparative assessment of 24 pigment dusts reveals analogue inhalation effects

A comparative analysis of 24 short-term inhalation studies with pigments revealed that while all pigments were well-tolerated without signs of systemic toxicity, most caused pulmonary inflammation and a slight to moderate increase in lung weight and neutrophil infiltration. The pathological and histopathological effects and changes observed were reversible at low and mid-level concentrations and declined within the 21 days recovery at the maximum concentration of 60 mg/m³. The slight to moderate epithelial hypertrophy and hyperplasia of the airways is considered being non-specific and adaptive. Benchmark calculations showed a 10 % lung weight increase and neutrophil infiltration at 5-20 mg/m³. Exposure levels above 30 mg/m³ ended up in lung overload and impaired alveolar macrophage mediated lung clearance. Pigment particles showed a consistent effect pattern of particle-related pulmonary inflammation after short-term exposure, which was transient in nature below lung overload causing concentrations. Sub-chronic inhalation studies for three of the pigments tested confirmed the identified effect-pattern and the absence of substance-specific or chemical class-related effects. Consequently, classification and labelling according to the regulatory guidance values and criteria in place is not considered meaningful. The establishment of clear definitions, criteria and human exposure limits for poorly soluble particles is considered a pragmatic approach.