Simple Flow‐through Solubility Measurement Apparatus and its Effectiveness for Hazard Assessment of Particles/Fibers

Abstract

assessment, Biopersistence, Inhalation, Intratracheal instillation Biopersistence of respirable particles in the lung is an important indicator for estimating the effects of the particles on the lung 1) , and its relationship with physicochemical properties of particles has been studied 2‐4) . We previously reported that long and insoluble fibers persist in the lung for a long time 5‐7) . International Agency for Research on Cancer summarized that as the solubility per unit surface area of vitreous fibers decreases, the biopersistence of fibers longer than 20 ∝m increases, producing histopathological changes 8) . If the correlation between such physicochemical factors and the biopersistence in the lung is clarified quantitatively, the measurement of these factors is available as a preliminary screening test for the hazard level of new chemical substances prior to conducting animal experiments. Focusing on the solubility among these physicochemical factors, a measurement system for asbestos substitutes was previously proposed 9) , and it indicated a relationship between solubility of long fiber and lung injury. This system is very precise but requires much time and effort because of the simulation of physiological conditions. Respirable dusts needed to be investigated for their health effects in the working environment contain not only long fibers and also small particles and short fibers, therefore it is important to measure the solubility of these small dusts simply and rapidly and to investigate the relation between their solubility and lung injury. In this study, the solubility of 6 types of dust, two respirable particles and three short fibers (>20 ∝m, 20 ∝m, 30%), was determined using a simple apparatus devised by us, in which the solutions surrounding the samples change continuously. In addition, the relationship between the solubility determined in this experiment and the biopersistence in the lung and pathological changes in intratracheal injection and inhalation exposure in our previous rat studies was investigated, in order to determine whether or not solubility has potential as an indicator for estimating the effects of particles and fibers on the lung. Materials and Methods Four types of fibers and 2 types of particle were used as the samples. They were magnesium sulfate whisker (MW; UBE Industries, Japan), calcium silicate fiber (CF; UBE Industries, Japan), magnesium silicate fiber (MF; NICHIAS corporation, Japan), potassium octatitanate whisker (JFM standard reference sample named PT1; Japan Fibrous Materials Research Association (JFMRA)), crystalline silica (CS; US Silica company, USA) and limestone (LS) from a mine in Japan. Electron micrographs of the respective samples are shown in Fig. 1. The abbreviated names, chemical compositions and geometrical configurations of the respective substances are shown in Table 1. The geometric mean diameter and length (geometric standard deviation) of the fibers were determined from their electron micrographs and the geometric mean diameters (geometrical standard deviation) of the particles were determined using a particle size analyzer (Microtrac FRA, Nikkiso, Japan). The outline of the solubility measurement apparatus by the flow-through system is shown in Fig. 2. One milligram of sample was suspended in the solution between the 0.22-∝m membrane filter on the inlet side and the outlet side of a cassette of a 37-mm air sampler. Phosphate buffered saline (0.01 M, pH 7.2) flowed upward from the lower part of this cassette at a rate of 12 ml/h. The effluent passing through the cassette was collected from the upper part at different times to determine the pH and to quantify the ion concentrations of the main components of the sample. The main components in the effluent (magnesium for MW, silicon for CF, MF and CS, titanium for PT1 and calcium for LS) were determined using an Inductively Coupled Plasma Atomic Emission Spectrometer (ICP-AES, SPS-1500R, SII, Japan) and the dissolved amounts of the respective samples were calculated from the contents of the elements by percentage of the samples.