Richard W. Mast

Chronic Inhalation Toxicity of a Kaolin-Based Refractory Ceramic Fiber in Syrian Golden Hamsters

AbstractKaolin-based refractory ceramic fiber (RCF) is a man-made vitreous fiber used primarily in industrial high-temperature applications, especially for insulation of furnaces and kilns. Because of its increasing use and potential for human exposure, a chronic toxicity/ carcinogenicity inhalation study was conducted in Syrian golden hamsters. Two groups of 140 weanling male hamsters were exposed via nose-only inhalation to either HEPA-filtered air (chamber controls) or 30 mg/m3 (-220 fibers/cm3) of “size-selected” RCF fibers (1 µm in diameter and -25 /jm in length) for 6 h/day, 5 dayslwk for 18 mo. They were then held unexposed until -20% survival (20 mo). A positive control group of 80 hamsters was exposed to 10 mg/m3 chrysotile asbestos (0.09 µm average diameter and 2.2 µm average length). Groups of 3 hamsters were sacrificed at 3, 6, 9, 12, 15, and 18 mo to follow the progression of lesions. Additional groups of 3 hamsters were removed from exposure at 3, 6, 9, and 12 mo and were held until 18 mo (r...

Safety assessment of DHA-rich microalgae from Schizochytrium sp. Part V: target animal safety/toxicity study in growing swine

The purpose of this study was to determine the potential toxicity of docosahexaenoic acid (DHA)-rich microalgae (DRM) from Schizochytrium sp., administered in the diet of growing swine. DRM was administered in the diet to groups of castrated male growing pigs (mixed commercial breeds, Landrace & Large White) reared from early weaned (weighing approximately 20 lbs) to approximately 250-270 lbs. Over the course of the 120 day study, animals were fed ad libitum four DRM treatment diets, each designed to optimize weight gain over the growing cycle, and a control diet. DRM was incorporated into the diet of the first treatment group at a level delivering 2.680 kg DRM per pig over the course of 120 days (a constant, whole-life exposure) equating to 598 g DHA per pig. DRM was incorporated into finisher diets only (administered over the last 42 days of the growing cycle) to treatment groups 2, 3, and 4 delivering 1.169, 3.391, and 5.746 kg DRM per pig (261, 756, and 1281 g DHA per pig). These levels represent approximately 1, 3, and 5 times the anticipated commercial dose and were delivered in a feeding strategy designed to mimic commercial use. Vitamin E was added to all diet groups to provide supplementary dietary antioxidant given the high content of polyunsaturated fat in DRM. There were no statistically significant treatment-related effects in clinical observations, body weights, food consumption, mortality, hematologic values, gross necropsy findings, organ weights or histopathology. The only DRM treatment-related changes were higher weight gain and feed conversion efficiency, anticipated results based on the increased fat content in the experimental DRM treatments. This study demonstrates that administration of DRM (at up to five times the anticipated commercial dose) did not produce any treatment-related adverse effects in commercial strains of swine.

REFRACTORY CERAMIC FIBER: Toxicology, Epidemiology, and Risk Analyses—A Review

Refractory ceramic fiber (RCF) is an energy-efficient, high-temperature insulation, used principally in industrial furnaces, heaters, and reactors. Prior to the 1980s, there were few publications dealing with the potential health effects of this material. However, with the advent of higher energy costs and the need for thermally efficient high-temperature insulating materials, production of RCF grew rapidly, as did interest in its potential health effects. This article provides a comprehensive and integrated review of the toxicology (in vitro and in vivo), epidemiology, and risk analysis literature of RCF. Based on the available literature, we conclude that an occupational exposure of 0.5 fibers per cubic centimeter (cm(3)) [8-h time-weighted average (8-h TWA)] results in an occupational health risk no greater than 9.1 x 10(-5).Refractory ceramic fiber (RCF) is an energy-efficient, high-temperature insulation, used principally in industrial furnaces, heaters, and reactors. Prior to the 1980s, there were few publications dealing with the potential health effects of this material. However, with the advent of higher energy costs and the need for thermally efficient high-temperature insulating materials, production of RCF grew rapidly, as did interest in its potential health effects. This article provides a comprehensive and integrated review of the toxicology (in vitro and in vivo), epidemiology, and risk analysis literature of RCF. Based on the available literature, we conclude that an occupational exposure of 0.5 fibers per cubic centimeter (cm3) [8-h time-weighted average (8-h TWA)] results in an occupational health risk no greater than 9.1 x 10-5.

Safety Assessment of DHA-Rich Microalgae from Schizochytrium sp.: IV. Mutagenicity Studies

The purpose of this study was to determine the potential toxicity of docosahexaenoic acid-rich microalgae from Schizochytrium sp. (DRM), administered in the diet to rats for at least 13 weeks. DRM was administered in the diet to groups of 20 male and 20 female Sprague-Dawley derived rats (Crl:CD(SD)BR) to provide dosages of 0, 400, 1500, and 4000 mg/kg/day for at least 13 weeks. DRM contained high levels of fat (approximately 41% w/w) of which long-chain highly unsaturated fatty acids (PUFAs) were a major component. Vitamin E acetate was added to DRM at manufacture to provide supplementary dietary antioxidant given the highly unsaturated fat content of DRM. Untreated controls received the basal diet only. An additional group of 20 males and 20 females received basal diet mixed with fish oil (Arista) to provide a target dosage of 1628 mg/kg/day, an amount of fat comparable to that received by rats administered the highest dose of DRM. Vitamin E acetate was also added to the fish oil to provide a comparable level of dietary antioxidant provided to high-dose DRM rats. There were no treatment-related effects in clinical observations, body weights or weight gains, food consumption, hematologic or urinalysis values, gross necropsy findings, or organ weights and there were no deaths. The only treatment-related changes in clinical chemistry parameters were decreases in high-density lipoproteins and cholesterol in the DRM and fish oil groups when compared to the untreated controls. These changes were expected based on the high PUFA content of DRM and fish oil. There were no microscopic findings suggestive of toxicity. Periportal hepatocellular fat vacuolation (accumulation of fat) was observed only in the livers of female rats in both the DRM (all dosages) and fish oil groups. This finding was expected given the higher fat content of both the DRM and the fish oil diets compared to the basal diet fed to the untreated controls. A slight increase in the incidence, but not severity, of cardiomyopathy was observed only in the 4000 mg/kg/day DRM males. This finding was not considered adverse because cardiomyopathy occurs spontaneously in rats and especially male rats of the Sprague-Dawley strain when fed high levels of fat. Since cardiomyopathy does not develop in other species including primates fed high-fat diets, its occurrence in rats is considered to have little relevance to human health. This study demonstrates that administration of DRM did not produce any treatment-related adverse effects in Sprague-Dawley rats of relevance to humans at dosages up to 4000 mg/kg/day for 13 weeks.

Deposition of Refractory Ceramic Fibers (RCF) in the Human Respiratory Tract and Comparison with Rodent Studies

A mathematical model has been developed to calculate the deposition of refractory ceramic fibers (RCF) in the human respiratory tract. For a typical size distribution of airborne RCF found in the work place, the fractional deposition and size distribution of deposited fibers in various regions of the respiratory tract are determined. These results are compared with those obtained earlier in rats and hamsters. The deposition fraction in the human lung is higher consisting of more coarse and long deposited fibers. This is caused by less efficient filtration of RCF in the human extrathoracic airways. Over the same exposure period however, total number of fibers deposited in the pulmonary region of the humans lung is about 5–10 times smaller per gram of lung or 1–2.5 times smaller per unit lung surface area than the rodents, depending upon the mode of breathing.