Survey of the biological effects of refractory ceramic fibres: overload and its possible consequences.

This paper summarizes the biological effects of refractory ceramic fibres (RCFs). RCFs are aluminosilicate glass insulation wools with similar chemical properties to other synthetic vitreous fibres (SVFs) or 'man-made vitreous fibres' (MMVFs). There is concern that RCFs could be significantly more pathogenic than other SVFs. This paper critically reviews the data on which this perception is based. Morbidity studies on workers in RCF manufacturing indicated that, in the United states, RCF exposure was associated with an increased incidence of pleural plaques and in both the united states and Europe with statistically significant changes in some measures of lung function (though not at present exposure levels). No interstitial fibrosis was found. An ongoing mortality study of limited statistical power has failed to indicate any increased incidence of lung cancer or mesothelioma. Findings in several early animal studies led to a large series of inhalation studies where rats exposed to high levels of RCF developed fibrosis and tumours but not those exposed to other SVFs. Similarly hamsters exposed to one sample (RCF1) developed mesothelioma. Subsequent analyses of the data indicated that the RCF used in these experiments had a significantly greater proportion of non-fibrous particles than those present in the other types of SVFs tested or in workplace air. Short-term studies indicated that pulmonary overload occurred at the same as RCF tissue burdens as those in the long-term animal bioassay. When RCFs were prepared in the same way as the other SVFs, a sample resulted with a more representative ratio of particles to fibres; this sample did not produce overload in short-term tests. SVFs have various abilities to persist in the lung tissue and thus accumulate to varying degrees. It is suggested that biopersistence is a key property. While RCFs are among the more persistent they are similar to many other fibre types. The scientific and regulatory implications of these findings are examined.

Interspecies comparisons of the toxicity of asbestos and synthetic vitreous fibers: a weight-of-the-evidence approach.

This analysis reviews the available literature on interspecies comparisons of the toxicity of asbestos and synthetic vitreous fibers (SVFs). This topic is of substantial practical importance because most quantitative risk analyses on the effects of inhalation of SVFs are based upon extrapolation of data from rodent inhalation studies. Available information on interspecies comparisons for both dosimetry (the relation between exposure concentration and fiber lung burden) and potency (the relation between lung burden and disease) is summarized. Dosimetry models indicate that, on a normalized basis, fiber deposition and clearance rates are lower in humans than rats. Potency is less well understood than dosimetry, in part because the source of relevant human data is asbestos studies, which are adequate to demonstrate hazard, but are problematic in other regards. There are significant interspecies differences between the mouse, hamster, rat, and human. The available evidence suggests that the rat is preferable as a model for the human. Rats develop fibrosis at comparable lung burdens [10(6) long (> 20 microm length) fibers per gram of dry lung] to those in humans. This analysis concludes that, on a weight-of-evidence basis, there is no reason to conclude that humans are more sensitive to fibers than rats with respect to the development of lung cancer.

A review of the Food and Drug Administration risk analysis for polychlorinated biphenyls in fish.

This paper reviews the Food and Drug Administration (FDA) analysis of the risk to humans from consuming fish contaminated with polychlorinated biphenyls (PCBs). In brief, the FDA methodology employed "high" dose experiments on animals and extrapolated the observed rates of certain types of cancer at these elevated doses to the low doses found in human diets. These extrapolations were then used to define a recommended tolerance level of 5 ppm, and proposed reduction to 2 ppm, for fish sold in interstate commerce. Unfortunately, as is shown here, such a procedure is extremely sensitive to the basis for extrapolation. Important elements of the FDA analysis include the following: (i) FDA assumed a particular form of the dose-response model: the one-hit model. Many other models have been proposed and, on balance, appear equally plausible. These models estimate lower risks than does the one-hit model. (ii) FDA calculated 99% upper confidence bounds on these risks and, moreover, emphasized cases of fish eaters who consume greater amounts of PCB-contaminated fish than do 98.5% of the U.S. population. (iii) FDA based PCB ingestion computations on consumption of raw fish, whereas most fish are cooked before eating, and it is known that PCB levels in cooked fish are lower than PCB levels in raw fish. (iv) FDA based estimates of cancer risk on the assumption that PCB levels in fish would be constant over the nominal 70-year human life span used in the FDA "lifetime risk" computation. Recent data suggest that PCB levels have been declining in fish (particularly in sport fish) and humans as well. Such trends imply significantly lower cumulative lifetime PCB doses than were assumed in the FDA analysis. (v) FDA assumed that humans and test animals are equally sensitive to PCB ingestion when measured on a parts per million in diet basis. Extrapolations on an equivalent consumption per unit of body weight, thought appropriate by most researchers, result in much lower health risks. In short, when confronted with methodological choices, the FDA consistently selected "worst case" or conservative assumptions over other alternatives of at least equal plausibility. This philosophy of choice was explicitly acknowledged by the FDA. What was omitted from the FDA analysis, however, was the possible degree of overstatement of these risks. The results of replicate risk computations using alternative assumptions to examine the possible magnitude of overstatement of health risk are summarized in Table 12. As can be seen, this overstatement could easily account for a discrepancy of several orders of magnitude between actual and calculated risks.(ABSTRACT TRUNCATED AT 400 WORDS)

The random-effects model applied to refractory ceramic fiber data.

Refractory ceramic fiber (RCF) is a valuable, high-temperature, insulating material with a variety of industrial uses. Because some fibers are respirable by humans and RCF is relatively durable in simulated lung fluids, RCF may pose a health hazard in the workplace. The RCF industry has established a comprehensive product stewardship program (PSP) to identify, quantify, and manage risks. One key element of this PSP is a workplace monitoring program. This paper analyzes monitoring data collected as part of a Consent Agreement with the U.S. Environmental Protection Agency over the period from 1993 to 1998. More specifically, this paper applies the random-effects model (REM) to data collected at several Unifrax plants and applicable to several groups of workers. The REM fits the RCF data well. Depending upon the plant and the functional job category values of the variance of the log-transformed time-weighted average workplace concentrations range from slightly less than 0.5 to 1.0. The estimated intraclass correlations (ratio of the between-worker variance to the total variance) were less than 0.4, and most were less than 0.2. Implications of these findings are examined. Use of the REM in the development of a workplace respiratory policy is described. Finally, two possible criteria for measuring compliance with an occupational exposure limit are reviewed: an "overexposure" criterion developed by Rappaport and co-workers and a conventional "no exceedance" criterion reportedly used by regulatory agencies. The overexposure criterion is logically correct for potential toxicants with chronic effects. For representative values of statistical parameters for RCF from the plants considered, the overexposure criterion is less stringent.

A multiyear workplace-monitoring program for refractory ceramic fibers.

This paper summarizes interim results of a 5-year workplace monitoring program conducted by firms belonging to the Refractory Ceramic Fibers Coalition (RCFC) pursuant to a Consent Agreement with the U.S. EPA. The exposure monitoring program is part of a model Product Stewardship Program (PSP) developed by RCFC. This paper reviews the refractory ceramic fiber (RCF) industry, findings of animal bioassay and epidemiological investigations, and the regulatory approach used by EPA. The scope, protocols, sample collection budgets, and experimental design of the monitoring program are summarized. In brief, the program will gather 720 time-weighted average (TWA) workplace concentration measurements annually, partitioned among 8 functional job classifications, both from plants that manufacture and from those that process or use RCF. Statistical analyses reveal that: workplace airborne RCF concentration data are approximately log-normally distributed, 93% of workplace TWAs are beneath the industry's recommended exposure guideline of 1 fiber per cubic centimeter (f/cc), there are significant differences in average workplace RCF concentrations among job types, and PSP activities are effective in lowering workplace exposure. Results of this effort provide an interesting illustration of a successful cooperative effort between a responsible industry and regulatory agencies.

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).

A multiyear workplace-monitoring program for refractory ceramic fibers: findings and conclusions.

Results of a monitoring program carried out by members of the Refractory Ceramic Fibers Coalition as part of a Consent Agreement with the U.S. Environmental Protection Agency to measure workplace concentrations of refractory ceramic fiber (RCF) are presented. More than 700 personal monitoring samples were collected and analyzed annually from workers in RCF production and processing plants, as well as from those employed by customers/end users. The data indicate that (i) approximately 90% of time-weighted average (TWA) workplace concentrations are below the industry's recommended exposure guideline of 1 fiber per cubic centimeter TWA; (ii) workplace concentrations vary with functional job category; (iii) concentrations are approximately lognormally distributed; (iv) workplace concentrations are generally decreasing; (v) there are significant differences in workplace concentrations among plants operated by both RCF producers and customers; (vi) equations can be developed to interconvert data analyzed using different measurement techniques and counting rules; (vii) usage of respirators varies with the functional job category of the worker and the average fiber concentration; and (viii) workplace samples differ from those used in animal inhalation experiments in terms of the ratio of respirable particles to fibers.

The development and use of respirator response functions as part of a workplace exposure monitoring program for control of potential respiratory hazards.

The traditional hierarchy of measures for control of potential respiratory hazards in the workplace includes (in order of preference) engineering controls, workplace practices, and use of respiratory protection. Although third in this hierarchy, respirators can be an important component of the control mix-particularly for difficult-to-control jobs, as an interim measure (pending implementation of other controls), and in cases where exposure is intermittent. One of the problems associated with the use of respirators as a control measure is that valid and adequate data on respirator usage are often not available. Absent these data it is difficult to determine the practical effectiveness of respirators and exposure calculations which include the protective effect of respirators are speculative. This paper presents models (and appropriate statistical fitting techniques) suitable for quantification of respirator usage and defines three potentially useful measures of effectiveness for a respirator program. These models are illustrated with monitoring data on refractory ceramic fiber (RCF) developed as part of a Consent Agreement between the RCF industry and the U.S. Environmental Protection Agency. For this substance there are extensive and comprehensive monitoring data available. The models and methods of analysis may prove applicable for other potential respiratory hazards in the workplace.

Workplace monitoring of refractory ceramic fiber in the United States.

This paper summarizes data from a comprehensive workplace exposure monitoring program for refractory ceramic fiber (RCF) conducted since 1990, including data collected under a 5-year consent agreement (1993-1998) between the U.S. Environmental Protection Agency and the Refractory Ceramic Fibers Coalition. It presents additional data and analyses, which complement an earlier article published in this journal (L. D. Maxim et al., 1997, Regul. Toxicol. Pharmacol. 26, 156-171). As part of this exposure monitoring program, data were collected at plants operated by RCF manufacturers and at customer facilities. Beginning in 1993, at least 720 samples (each sample consisting of one or more cassettes) were collected annually, distributed according to a stratified random sampling plan. The strata consisted of workers in eight functional job categories (FJCs) at manufacturing and customer plants. Time-weighted average (TWA) and task length average data were gathered and analyzed using phase contrast optical microscopy and (for a subset of samples) transmission electron microscopy methods. Data on respirator usage (by type) were also collected. Statistical analysis indicates that there are significant differences in TWA fiber concentrations (exposure) among FJCs (installation, finishing, and removal categories have the highest average concentrations), that workplace concentration data are approximately lognormally distributed, and that weighted average fiber concentrations decreased over the period from 1990 to 1998-although trend curves leveled out as exposures have decreased and further improvements became more difficult. Material differences exist in exposure between RCF manufacturers and their customers (largely because the mix of jobs differ), but these differences have narrowed over the years. Respirator usage varies with exposure. Respirator data are used to derive improved estimates of actual worker exposure. Alternative criteria for selecting FJCs for control efforts are defined and illustrated. Lessons learned for future monitoring efforts are summarized.

Retention modeling of refractory ceramic fibers (RCF) in humans.

A mathematical retention model has been developed to predict the lung burden and size distribution of kaolin refractory ceramic fibers (RCF) in the pulmonary region of the human lung during exposure. Fiber dissolution, breakage, and differential clearance are considered in this model; rates for these processes are obtained by extrapolation from available data on laboratory rats. The lung burden predicted by this model is in general agreement with fiber counts from three factory workers. An important prediction from this study is that clearance of RCF is not significantly impaired at a fiber concentration beneath 10 f/cm3 during occupational exposure.

Hazard assessment and risk analysis of two new synthetic vitreous fibers.

Isofrax and Insulfrax are two new synthetic vitreous fibers (SVFs) developed for high-temperature insulation (1800-2300 degrees F) applications. In an attempt to significantly reduce or eliminate the potential of adverse health effects, these two fibers were specifically designed to have high solubility and, thus, low in vivo biodurability. In this paper, we review the effects of chemical composition on biodurability, in vitro fiber dissolution rates (K(dis)), and the relevance and relationship of K(dis) to pulmonary fibrosis and lung tumors in chronic rat inhalation studies. We also examine the correlations between K(dis) and weighted in vivo half-life (t(0.5)) of long fibers (>20 microm) and their relation to pulmonary effects in chronic rat inhalation bioassays. Predictions for outcomes of inhalation bioassays and development of nonsignificant risk levels of exposure are provided. Additionally, justification for the use of inhalation versus noninhalation animal data is provided as is a brief review of human health effects of SVFs. We conclude, inter alia, that Isofrax and Insulfrax have low biodurability, would not be expected to produce either pulmonary fibrosis or lung tumors in a well-designed animal inhalation bioassay, have weighted half-lives beneath the threshold established by the European Union for classification as a carcinogen, and based on epidemiological data for SVFs would not be expected to result in incremental cancer in human cohorts. Finally, it is estimated that approximately 90% of workplace exposure concentrations of these materials would be beneath 1 f/cc. At a concentration of 1 f/cc, neither fiber would be expected to result in an incremental working lifetime cancer risk greater than 10(-5).