Total-body Exposure to Metal Sensitizers: Inhalation, Ingestion, and Skin Contact

Abstract

O-30A6-4 Background/Aims: Exposures to sensitizing metals are a significant public and occupational health problem. Once sensitized, a person must avoid repeated exposures to specific metal(s) to prevent elicitation of adverse responses. Exposures may occur via inhalation, ingestion, and skin contact, with each pathway contributing to the total-body insult. The purpose of this study was to evaluate the solubility and absorption potential of 2 model metal allergens, cobalt, and beryllium, in the lung, gastrointestinal, and skin compartments. Methods: Solubility of cobalt and beryllium metal particles was evaluated using 1 or more biologically relevant artificial solvents: lung airway lining fluid, lung alveolar macrophage phagolysosomal fluid, gastrointestinal fluid, and skin sweat. Solubility tests provided estimates of bioaccessibility (amount available for absorption). Absorption across biological barriers was estimated using published human and animal toxicology literature. Results: Dissolution rates for cobalt metal particles, in units of g/(cm2 × day), were fastest in gastrointestinal fluid (3.7 ± 1.6 × 10 − 4) and slower in skin sweat (4.4 ± 0.4 × 10 − 5), lung alveolar macrophage phagolysosomal fluid (2.8 ± 0.8 × 10 − 5), and airway lining fluid (1.0 ± 0.3 × 10 − 5). For beryllium metal particles, dissolution rates were fastest in gastrointestinal fluid (4.1 ± 0.2 × 10 − 7) and slower in phagolysosomal fluid (1.1 ± 1.4 × 10 − 7), skin sweat (1.7 ± 0.6 × 10 − 8), and airway lining fluid (1.5 ± 0.8 × 10 − 9). Literature indicates the absorption of particulate cobalt compounds is 30% via inhalation, 3% to 50% via ingestion, and 0.024% and 3.6% via intact and abraded skin, respectively. Absorption of particulate beryllium compounds is <1% via ingestion. In the absence of inhalation and skin absorption values for particulate beryllium, levels were assumed to be similar to divalent cations such as cobalt. Conclusion: Cobalt and beryllium metal particles are soluble in biological fluids and may be absorbed via multiple exposure pathways. Based on the range of absorption values among biological compartments, systemic dose may be limited by dissolution rates.