Estimating rock and slag wool fiber dissolution rate from composition.

A method was tested for calculating the dissolution rate constant in the lung for a wide variety of synthetic vitreous silicate fibers from the oxide composition in weight percent. It is based upon expressing the logarithm of the dissolution rate as a linear function of the composition and using a different set of coefficients for different types of fibers. The method was applied to 29 fiber compositions including rock and slag fibers as well as refractory ceramic and special-purpose, thin E-glass fibers and borosilicate glass fibers for which in vivo measurements have been carried out. These fibers had dissolution rates that ranged over a factor of about 400, and the calculated dissolution rates agreed with the in vivo values typically within a factor of 4. The method presented here is similar to one developed previously for borosilicate glass fibers that was accurate to a factor of 1.25. The present coefficients work over a much broader range of composition than the borosilicate ones but with less accuracy. The dissolution rate constant of a fiber may be used to estimate whether disease would occur in animal inhalation or intraperitoneal injection studies of that fiber.

Estimation of dissolution rate from in vivo studies of synthetic vitreous fibers.

Although the dissolution rate of a fiber was originally defined by a measurement of dissolution in simulated lung fluid in vitro, it is feasible to determine it from animal studies as well. The dissolution rate constant for a fiber may be extracted from the decrease in long fiber diameter observed in certain intratracheal instillation experiments or from the observed long fiber retention in short-term biopersistence studies. These in vivo dissolution rates agree well with those measured in vitro for the same fibers. For those special types of fibers, the high-alumina rock wool fibers that could not be measured in vitro, the method provides a way of obtaining a chemical dissolution rate constant from an animal study. The inverse of the in vivo dissolution rate, the fiber dissolution time, correlates well with the weighted half life of long fibers in a biopersistence study, and the in vivo dissolution rate may be estimated accurately from this weighted half-life.

Estimating in vitro glass fiber dissolution rate from composition.

A method is presented for calculating the dissolution rate constant of a borosilicate glass fiber in the lung, as measured in vitro, from the oxide composition in weight percent. It is based upon expressing the logarithm of the dissolution rate as a linear function of the composition. It was found that the calculated dissolution rate constant agreed with the measured value within the variation of the measured data in a set of compositions in which the dissolution rate constant ranged over a factor of 100. The method was shown to provide a reasonable estimate of dissolution over a considerably wider range of composition than what was used to determine the parameters, such as a set of data in which the dissolution rate constant varied over a factor of 100,000. The dissolution rate constant may be used to estimate whether disease would ensue following animal inhalation or intraperitoneal studies.

Quantitative risk assessment for a glass fiber insulation product.

California Proposition 65 (Prop65) provides a mechanism by which the manufacturer may perform a quantitative risk assessment to be used in determining the need for cancer warning labels. This paper presents a risk assessment under this regulation for professional and do-it-yourself insulation installers. It determines the level of insulation glass fiber exposure (specifically Owens Corning's R-25 PinkPlus with Miraflex) that, assuming a working lifetime exposure, poses no significant cancer risk under Prop65's regulations. "No significant risk" is defined under Prop65 as a lifetime risk of no more than one additional cancer case per 100,000 exposed persons, and nonsignificant exposure is defined as a working lifetime exposure associated with "no significant risk." This determination can be carried out despite the fact that the relevant underlying studies (i.e., chronic inhalation bioassays) of comparable glass wool fibers do not show tumorigenic activity. Nonsignificant exposures are estimated from (1) the most recent RCC chronic inhalation bioassay of nondurable fiberglass in rats; (2) intraperitoneal fiberglass injection studies in rats; (3) a distributional, decision analysis approach applied to four chronic inhalation rat bioassays of conventional fiberglass; (4) an extrapolation from the RCC chronic rat inhalation bioassay of durable refractory ceramic fibers; and (5) an extrapolation from the IOM chronic rat inhalation bioassay of durable E glass microfibers. When the EPA linear nonthreshold model is used, central estimates of nonsignificant exposure range from 0.36 fibers/cc (for the RCC chronic inhalation bioassay of fiberglass) through 21 fibers/cc (for the i.p. fiberglass injection studies). Lower 95% confidence bounds on these estimates vary from 0.17 fibers/cc through 13 fibers/cc. Estimates derived from the distributional approach or from applying the EPA linear nonthreshold model to chronic bioassays of durable fibers such as refractory ceramic fiber or E glass microfibers are intermediate to the other approaches. Estimates based on the Weibull 1.5-hit nonthreshold and 2-hit threshold models exceed by at least a factor of 10 the corresponding EPA linear nonthreshold estimates. The lowest nonsignificant exposures derived in this assessment are at least a factor of two higher than field exposures measured for professionals installing the R-25 fiberglass insulation product and are orders of magnitude higher than the estimated lifetime exposures for do-it-yourselfers.

Comparison of biopersistence of experimental glass fibres in the lung and peritoneal cavity.

Thirty three female Fischer-344 rats were intra-peritoneally (IP) injected with 5 mg of an experimental glass fibre designated X7753. This fibre type had an in vitro dissolution rate of 600 ng cm-2h-1. Groups of three rats were killed at various times up to one year after injection. The diaphragm and any fibre nodules were removed from the carcass and separately digested using hypochlorite solution, to recover the fibres. The number and morphometry of the fibres was measured using phase contrast optical microscopy (PCOM) and semi-automatic image analysis. The data obtained were compared to the previous studies of the durability of the X7753 fibres in the lung.

The durability and distribution of glass fibres in the rat following intra-peritoneal injection.

Intra-peritoneal (IP) injection is being recommended as a means of assessing potential carcinogenicity of MMF following inhalation. Little is known of the behaviour of fibres in the peritoneal cavity or its relevance to the lung. This study considered both the biopersistence and the distribution of dose following IP injection of fibres. Biopersistence of fibres in the peritoneal cavity has been compared with that observed previously in the lung. Marked differences were found, with long fibres (> 20 microns) being more durable in the peritoneal cavity than in the lung. Breakage could not account for this finding, whereas differences in dissolution could. The behaviour of fibres and powders and their distribution in the peritoneal cavity following injection of different masses is reported. Distribution of dose depended on injection mass, with masses of < 1.5 mg showing even uptake onto the surfaces of the peritoneal organs, and higher masses resulting in the development of nodules of injection material, free in the peritoneal cavity, or loosely bound to the peritoneum. With fine powder, some clearance was observed over the first 48 h after IP injection, but not with fibres. The findings on both durability and distribution of dose following IP injection have implications on the justification for the use of IP injections in assessment of potential carcinogenicity of fibres following inhalation.

Role of fiber dissolution in biological activity in rats.

This report deals with the role of dissolution in removing long fibers from the lung and with a mathematical model that predicts chronic effects in rats following inhalation or intraperitoneal (i.p.) injection of fibers. Results of intratracheal instillation studies and inhalation studies in rats demonstrate clearly that long vitreous fibers dissolve in vivo at about the same rate measured in vitro in fluid designed to stimulate the extracellular lung fluid. For the glass, rock, and slag wool fibers tested, dissolution removed most of the fibers longer than 20 microns inhaled into the rats' lungs within 6 months after both short-term (5 days) and long-term (1 to 2 years) exposures. A mathematical model was developed that is based on fiber dissolution and allows one to predict the development of chronic lung diseases in rats. The model predicted the incidence of fibrosis and lung tumors in a series of recent inhalation studies and tumors following ip injection to within about the error of the experiments. The model suggests that all fibers, regardless of their dissolution rate in lung fluid, can produce tumors after ip injection because the dose can be unlimited by this route. After inhalation, in contrast, dissolution of many types of long vitreous fibers occurs rapidly, and disease does not ensue for these fibers.

The behavior of glass fibers in the rat following intraperitoneal injection.

Potential carcinogenicity of fibers is believed to be determined by three factors: the dose, dimensions and durability of the fibers concerned. Currently there is considerable debate on the appropriateness of using results from intraperitoneal (i.p.) injection studies to predict the potential carcinogenicity of airborne fibers following inhalation. For ip results to have any significance to potential inhalation hazards, there should be some relation between the biopersistence, dose, and dose distribution of fibers in the serosal cavity and in the lung. Preliminary results on the durability of one experimental glass fiber in the peritoneal cavity suggest differences in dissolution when compared with durability in the lung. In the lung, the diameters of the long fibers (> 20 microns) were observed to decline at a rate consistent with their exposure to a neutral pH environment. The diameter of shorter fibers declined much more slowly, consistent with exposure to a more acidic environment such as is found in the phagolysosomes of alveolar macrophages. In the peritoneal cavity all fibers, regardless of length, dissolved at the same rate as short fibers in the lung. The effect of dose on the distribution of fibers in the peritoneal cavity was investigated using similar experimental glass fibers and compared with that of a powder made from ground fibers. For both materials at doses up to 1.5 mg, material was taken up by the peritoneal organs roughly in proportion to their surface area. This uptake was complete 1-2 days after injection. At higher doses, the majority of the material in excess of this 1.5 mg formed clumps of fibers (nodules) which were either free in the peritoneal cavity or loosely bound to peritoneal organs. These nodules displayed classic foreign body reactions with an associated granulomatous inflammatory response. The findings on both durability in the peritoneal cavity and the presence of two distinct populations of material following i.p. injection have implications for the justification of the use of i.p. injections to assess potential carcinogenicity of fibers following inhalation.

Biopersistences of man-made vitreous fibers and crocidolite fibers in rat lungs following short-term exposures.

Biopersistence of commercial man-made vitreous fibers (MMVF) and crocidolite were studied in Fischer 344 rats. MMVF used were size-selected to be rat-respirable, and rats were exposed nose-only 6 h/day for 5 days to gravimetric concentrations (30 mg/m3) of two fiber glass compositions--a rockwool, and a slagwool--or to 10 mg/m3 of long-fibered crocidolite, or to filtered air. Animals were sacrificed at 1 hr, 1, 5, 31, 90, 180, 270, 365, and 545 days after exposure stopped. Fibers were recovered from digested lung tissue to determine changes in concentrations (fibers/mg dry lung) and fiber retentions (expressed as percent of day 1 retention [PR]) for selected dimension categories. One-day average concentrations of lung-retained MMVF and crocidolite fibers, of diameter > or = 0.5 micron or > 20 microns in length, were nearly equal, permitting direct comparisons between MMVF and crocidolite. At 270 days average PR for MMVF > or = 0.5 micron in diameter were from 3 to 6 +/- 2% and 27 +/- 9% for crocidolite. For fibers > 20 microns, PR were 1 to 4 +/- 4% for MMVF and 37 +/- 20% for crocidolite. At 545 days, MMVF > 20 microns in length were at background level while concentration of crocidolite fibers > 20 microns in length remained at 2000 +/- 400 f/mg DL (dry lung), or 38 +/- 9% of day-1 retention. These results suggest strongly that MMVF dissolved or fractured in vivo whereas crocidolite fibers did not change.