Through the Act, Congress charged NIOSH with recommending occupational safety and health standards and describing exposure limits that are safe for various periods of employment. These limits include but are not limited to the exposures at which no worker will suffer diminished health, functional capacity, or life expectancy as a result of his or her work experience. By means of criteria documents, NIOSH communicates these recommended standards to regulatory agencies (including the Occupational Safety and Health Administration ), health professionals in academic institutions, industry, organized labor, public interest groups, and others in the occupational safety and health community. Criteria documents contain a critical review of the scientific and technical information about the prevalence of hazards, the existence of safety and health risks, and the adequacy of control methods.#
This criteria document is derived from reviews of information from human and animal studies of the toxicity of refractory ceramic fibers (RCFs) and is intended to describe the potential health effects of occupational exposure to airborne fibers of this material. RCFs are amorphous synthetic fibers produced by the melting and blowing or spinning of calcined kaolin clay or a combination of alumina, silica, and other oxides. RCFs belong to the class of synthetic vitreous fibers (SVFs)-materials that also include fibers of glass wool, rock wool, slag wool, and specialty glass. RCFs are used in commercial applications requiring lightweight, high-heat insulation (e.g., furnace and kiln insulation). Commercial production of RCFs began in the 1950s in the United States, and production increased dramatically in the 1970s. Domestic production of RCFs in 1997 totaled approximately 107.7 million lb. Currently, total U.S. production has been estimated at 80 million lb per year, which constitutes 1% to 2% of SVFs produced worldwide. In the United States, approximately 31,500 workers have the potential for occupational exposure to RCFs during distribution, handling, installation, and removal. More than 800 of these workers are employed directly in the manufacturing of RCFs and RCF products. With increasing production of RCFs, concerns about exposures to airborne fibers prompted animal inhalation studies that have indicated an increased incidence of mesotheliomas in hamsters and lung cancer in rats following exposure to RCFs. Studies of workers who manufacture RCFs have shown a positive association between increased exposure to RCFs and the development of pleural plaques, skin and eye irritation, and respiratory symptoms and conditions (including dyspnea, wheezing, and chronic cough). In addition, current and former RCF production workers have shown decrements in pulmonary function.
After evaluating this evidence, NIOSH proposes a recommended exposure limit (REL) for RCFs of 0.5 fiber per cubic centimeter (f/cm 3 ) of air as a time-weighted average (TWA) concentration for up to a 10-hr work shift during a 40-hr workweek. Limiting airborne RCF exposures to this concentration will minimize the risk for lung cancer and irritation of the eyes and upper respiratory system and is achievable based on a review of exposure monitoring data collected from RCF manufacturers and users. However, because a residual risk of cancer (lung cancer and pleural mesothelioma) may still exist at the REL, continued efforts should be made toward reducing exposures to less than 0.2 f/cm 3 . Engineering controls, appropriate respiratory protection programs, and other preventive measures should be implemented to minimize worker exposures to RCFs. NIOSH urges employers to disseminate this information to workers and customers. NIOSH also requests that professional and trade associations and labor organizations inform their members about the hazards of exposure to RCFs.
Executive Summary lung cancer. However, studies of worker populations with occupational exposure to airborne RCFs have shown an association between exposure and the formation of pleural plaques, increased prevalence of respiratory symptoms and conditions (dyspnea, wheezing, chronic cough), decreases in pulmonary function, and skin, eye, and upper respiratory tract irritation . Increased decrements in pulmonary function among workers exposed to RCFs who are current or former cigarette smokers indicate an apparent synergistic effect between smoking and RCF exposure . This finding is consistent with studies of other dustexposed populations. The implementation of improved engineering controls and work practices in RCF manufacturing processes and end uses have led to dramatic declines in airborne fiber exposure concentrations , which in turn have lowered the risk of symptoms and health effects for exposed workers.
In 2002, the Refractory Ceramic Fibers Coalition (RCFC) established the Product Stewardship Program (PSP), which was endorsed by the Occupational Safety and Health Administration (OSHA). Contained in the PSP were recommendations for an RCF exposure guideline of 0.5 fiber per cubic centimeter (f/cm 3 ) of air as a time-weighted average (TWA) based on the contention that exposures at this concentration could be achieved in most industries that manufactured or used RCFs. At this time, the available health data do not provide sufficient evidence for deriving a precise healthbased occupational exposure limit to protect The National Institute for Occupational Safety and Health (NIOSH) has reviewed data characterizing occupational exposure to airborne refractory ceramic fibers (RCFs) and information about potential health effects obtained from experimental and epidemiologic studies. From this review, NIOSH determined that occupational exposure to RCFs is associated with adverse respiratory effects as well as skin and eye irritation and may pose a carcinogenic risk based on the results of chronic animal inhalation studies.
In chronic animal inhalation studies, exposure to RCFs produced an increased incidence of mesotheliomas in hamsters  and lung cancer in rats . The potential role of nonfibrous particulates generated during inhalation exposures in the animal studies complicates the issue of determining the exact mechanisms and doses associated with the toxicity of RCFs in producing carcinogenic effects . The induction of mesotheliomas and sarcomas in rats and hamsters following intrapleural and intraperitoneal implantation of RCFs provided additional evidence for the carcinogenic potential of RCFs . Lung tumors have also been observed in rats exposed to RCFs by intratracheal instillation .
In contrast to the carcinogenic effects of RCFs observed in experimental animal studies, epidemiologic studies have found no association between occupational exposure to airborne RCFs and an excess rate of pulmonary fibrosis or The risk for mesothelioma at 0.5 f/cm 3 is not known but cannot be discounted. Evidence from epidemiologic studies showed that higher exposures in the past resulted in pleural plaques in workers, indicating that RCFs do reach pleural tissue. Both implantation studies in rats and inhalation studies in hamsters show that RCFs can cause mesothelioma. Because of limitations in the hamster data, the risk of mesothelioma cannot be quantified. However, the fact that no mesothelioma has been found in workers and that pleural plaques appear to be less likely in workers with lower exposures suggests a lower risk for mesothelioma at the REL.
Because residual risks of cancer (lung cancer and pleural mesothelioma) and irritation may still exist at the REL, NIOSH further recommends that all reasonable efforts be made to work toward reducing exposures to less than 0.2 f/cm 3 . At this concentration, the risks of lung cancer are estimated to be between 0.03/1,000 and 0.47/1,000 (based on extrapolations of risk models from Moolgavkar et al.  and Yu and Oberdorster ).
Maintaining airborne RCF concentrations below the REL requires a comprehensive safety and health program that includes provisions for the monitoring of worker exposures, installation and routine maintenance of engineering controls, and the training of workers in good work practices. Industry-led efforts have likewise promoted these actions by establishing the PSP. NIOSH believes that maintaining exposures below the REL is achievable at most manufacturing operations and many user applications, and that the incorporation of an action level (AL) of 0.25 f/cm 3 in the exposure monitoring strategy will help employers determine when workplace exposure concentrations are approaching the REL. The AL concept has been an integral element of occupational standards recommended in NIOSH criteria documents and in comprehensive standards promulgated by OSHA and the Mine Safety and Health Administration (MSHA).
NIOSH also recommends that employers implement additional measures under a comprehensive safety and health program, including hazard communication, respiratory protection programs, smoking cessation, and medical monitoring. These elements, in combination with efforts to maintain airborne RCF concentrations below the REL, will further protect the health of workers. xv Glossary FVC: Forced vital capacity or the maximum volume of air (in liters) that can be forcibly expired from the lungs following a maximal inspiration.

# High-efficiency particulate air (HEPA) filter:
A dry-type filter used to remove airborne particles with an efficiency equal to or greater than 99.97% for 0.3-m particles. The lowest filtering efficiency of 99.97% is associated with 0.3-m particles, which is approximately the most penetrating particle size for particulate filters.

# Inspirable dust:
The fraction of airborne particles that would be inspired through the mouth and nose of a worker.

# MAN:
A refractory ceramic fiber produced by the Johns Manville Company.

# Occupational medical monitoring (incorporating medical screening, surveillance):
The periodic medical evaluation of workers to identify potential health effects and symptoms related to occupational exposures or environmental conditions in the workplace. An occupational medical monitoring program is a secondary prevention method based on two processes, screening and surveillance.
Occupational medical screening focuses on early detection of health outcomes for individual workers. Screening may involve an occupational history assessment, medical examination, and medical tests to detect the presence of toxicants or early pathologic changes before the worker would normally seek clinical care for symptomatic disease. Occupational medical surveillance involves the ongoing evaluation of the health status of a group of workers through the collection and analysis of health data for the purpose of disease prevention and for evaluating the effectiveness of intervention programs.
Pleural plaques: Discrete areas of thickening that are generally on the parietal pleura and are most commonly located at the midcostal and posterior costal areas, the dome of the diaphragm, and the mediastinal pleura. Presence of plaques is an indication of exposure to a fibrous silicate, most frequently asbestos.

# Radiographic opacity:
A shadow on a chest X-ray film generally associated with a fibrogenic response to dust retained in the lungs . Opacities are classified by size, shape, location, and profusion according to guidelines established by the International Labor Office  www.ilo.org/public/english/support/publ/books.htm).

# Refractory ceramic fiber (RCF):
An amorphous, synthetic fiber (Chemical Abstracts Services No. 142844-00-6) produced by melting and blowing or spinning calcined kaolin clay or a combination of alumina (Al 2 O 3 ) and silicon dioxide (SiO 2 ). Oxides may be added such as zirconia, ferric oxide, titanium oxide, magnesium oxide, calcium oxide, and alkalies. The percentage (by weight) of components is as follows: alumina, 20% to 80%; silicon dioxide, 20% to 80%; and other oxides in smaller amounts.
Respirable-sized fiber: Particles >5 m long with an aspect ratio >3:1 and diameter 1.3 m.

# Shot:
Nonfibrous particulate that is generated during the production of RCFs from the original melt batch.
xvi

# Refractory Ceramic Fibers

# Glossary Standardized mortality ratio (SMR):
The ratio of the observed number of deaths (from a specified cause) to the expected number of deaths (from that same cause) that has been adjusted to account for demographic differences (e.g., age, sex, race) between the study population and the referent population.

# Synthetic vitreous fiber (SVF):
Any of a number of manufactured fibers produced by the melting and subsequent fiberization of kaolin clay, sand, rock, slag, etc. Fibrous glass, mineral wool, ceramic fibers, and alkaline earth silicate wools are the major types of SVF, also called man-made mineral fiber (MMMF) or man-made vitreous fiber (MMVF).
Thoracic-sized fiber: Particles >5 m long with aspect ratio >3:1 and a diameter <3 to 3.5 m.
Thoracic refers to particles penetrating to the thorax (50% cut at 10-m aerodynamic diameter).
Mineral and vitreous fibers with diameters 3 to 3.5 m have an aerodynamic diameter of approximately 10 m.
1 Recommendations for a Refractory Ceramic Fiber (RCF) Standard mesothelioma, and other adverse respiratory health effects (including irritation and compromised pulmonary function) associated with excessive RCF exposure in the workplace. Limiting exposures will also protect workers' eyes and skin from the mechanical irritation associated with exposure to RCFs. In most manufacturing operations, it is currently possible to limit airborne RCF concentrations to 0.5 f/cm 3 or less. Exceptions may occur during RCF finishing operations and during the installation and removal of RCF products, when the nature of job activities presents a challenge to meeting the REL. For these operations, additional protective measures are recommended. Engineering and administrative controls, respirator use, and other preventive measures should be implemented to minimize exposures for workers in RCF industry sectors where airborne RCF concentrations exceed the REL. NIOSH urges employers to disseminate this information to workers and customers, and RCF manufacturers should convey this information to downstream users. NIOSH also requests that professional and trade associations and labor organizations inform their members about the hazards of exposure to RCFs.

# Definitions and Characteristics

# Naturally Occurring Mineral Fibers
Many types of mineral fibers occur naturally. Asbestos is the most prominent of these fibers because of its industrial application. The
The National Institute for Occupational Safety and Health (NIOSH) recommends that exposure to airborne refractory ceramic fibers (RCFs) be controlled in the workplace by implementing the recommendations presented in this document. These recommendations are designed to protect the safety and health of workers for up to a 10-hr work shift during a 40-hr workweek over a 40-year working lifetime. Observance of these recommendations should prevent or greatly reduce the risks of eye and skin irritation and adverse respiratory health effects (including lung cancer) in workers with exposure to airborne RCFs. Preventive efforts are primarily focused on controlling and minimizing airborne fiber concentrations to which workers are exposed. Exposure monitoring, hazard communication, training, respiratory protection programs, and medical monitoring are also important elements of a comprehensive program to protect the health of workers exposed to RCFs. These elements are described briefly in this chapter and in greater detail in Chapter 9.

# Recommended Exposure Limit (REL)
NIOSH recommends that occupational exposures to airborne RCFs be limited to 0.5 fiber per cubic centimeter (f/cm 3 ) of air as a timeweighted average (TWA) concentration for up to a 10-hr work shift during a 40-hr workweek, measured according to NIOSH Method 7400 (B rules) .
This recommended exposure limit (REL) is intended to reduce the risk of lung cancer, asbestos minerals include both the serpentine asbestos (chrysotile) and the amphibole mineral fibers, including actinolite, amosite, anthophyllite, crocidolite, and tremolite . Since ancient times, mineral fibers have been mined and processed for use as insulation because of their high tensile strength, resistance to heat, durability in acids and other chemicals, and light weight. The predominant forms of asbestos mined and used today are chrysotile (~95%), crocidolite (<5%), and amosite (<1%).
For the purposes of this document, naturally occurring mineral fibers are distinguishable from synthetic vitreous fibers (SVFs) based on the crystalline structure of the mineral fibers. This property causes the mineral fibers to fracture longitudinally when subjected to mechanical stresses, thereby producing more fibers of decreasing diameter. By contrast, SVFs are amorphous and fracture transversely, resulting in more fibers of decreasing length until the segments are no longer of sufficient length to be considered fibers. Naturally occurring mineral fibers are generally more durable and less soluble than SVFs, a property that accounts for the biopersistence and toxicity of mineral fibers in vivo.

# RCFs
RCFs are a type of SVF; they are amorphous synthetic fibers produced from the melting and blowing or spinning of calcined kaolin clay or a combination of alumina (Al 2 O 3 ) and silicon dioxide (SiO 2 ). Oxides such as zirconia, ferric oxide, titanium oxide, magnesium oxide, calcium oxide, and alkalies may be added. The percentage of components (by weight) is as follows: alumina, 20% to 80%; silicon dioxide, 20% to 80%; and other oxides in smaller amounts. Like the naturally occurring mineral fibers, RCFs possess the desired qualities of heat resistance, tensile strength, durability, and light weight. On a continuum, however, RCFs are less durable (i.e., more soluble) than the least durable asbestos fiber (chrysotile) but more durable than most fibrous glass and other types of SVFs.

# SVFs
SVFs include a number of manmade (not naturally occurring) fibers that are produced by the melting and subsequent fiberization of kaolin clay, sand, rock, slag, and other materials. The major types of SVFs are fibrous glass, mineral wool (slag wool, rock wool), and ceramic fibers (including RCFs). SVFs are also frequently referred to as manmade mineral fibers (MMMFs) or manmade vitreous fibers (MMVFs).

# Sampling and Analysis
Employers shall perform air sampling and analysis to determine airborne concentrations of RCFs according to NIOSH Method 7400 (B rules) , provided in Appendix A of this document.

# Exposure Monitoring
Employers shall perform exposure monitoring as follows:
 Establish a workplace exposure monitoring program for worksites where RCFs or RCF products are manufactured, handled, used, installed, or removed.
 Include in this program routine area and personal monitoring of airborne fiber concentrations.
 Design a monitoring strategy that can be used to 1  Recommendations for a Refractory Ceramic Fiber Standard -evaluate a worker's exposure to RCFs, -assess the effectiveness of engineering controls, work practices, and other factors in controlling airborne fiber concentrations, and -identify work areas or job tasks in which worker exposures are routinely high and thus require additional efforts to reduce them.

# Sampling Surveys
Employers shall conduct exposure monitoring surveys to ensure that worker exposures (measured by full-shift samples) do not exceed the REL. Because adverse respiratory health effects may occur at the REL, it is desirable to achieve lower concentrations whenever possible. When workers are potentially exposed to airborne RCFs, employers shall conduct exposure monitoring surveys as follows:
 Collect representative personal samples over the entire work shift .
 Perform periodic sampling at least annually and whenever any major process change takes place or whenever another reason exists to suspect that exposure concentrations may have changed.
 Collect all routine personal samples in the breathing zones of the workers.
 If workers are exposed to concentrations above the REL, perform more frequent exposure monitoring as engineering changes are implemented and until at least two consecutive samples indicate that exposures no longer exceed the REL .
 Notify all workers of monitoring results and of any actions taken to reduce their exposures.
 When developing an exposure sampling strategy, consider variations in work and production schedules as well as the inherent variability in most area sampling .

# Focused sampling
When sampling to determine whether worker RCF exposures are below the REL, a focused sampling strategy may be more practical than a random sampling approach. A focused sampling strategy targets workers perceived to be exposed to the highest concentrations of a hazardous substance . This strategy is most efficient for identifying exposures above the REL if maximum-risk workers and time periods are accurately identified. Short tasks involving high concentrations of airborne fibers could result in elevated exposure over full work shifts.
Sampling strategies such as those used by Corn and Esmen , Rice et al. , and Maxim et al.  have been developed and used specifically in RCF manufacturing facilities to monitor airborne fiber concentration. In these strategies, representative workers are selected for sampling and are grouped according to dust zones, uniform job titles, or functional job categories. These approaches are intended to reduce the number of required samples and increase the confidence of identifying workers at similar risk.

# Area sampling
Area sampling may be useful in exposure monitoring to determine sources of airborne RCFs and to assess the effectiveness of engineering controls.

# Action Level
An action level (AL) at half the REL (0.25 f/cm 3 ) shall be used to determine when additional controls are needed or when administrative actions should be taken to reduce exposure to RCFs. The purpose of an AL is to indicate when worker exposures to hazardous substances may be approaching the REL. When air samples contain concentrations at or above the AL, the probability is high that worker exposures to the hazardous substance exceed the REL.
The AL is a statistically derived concept permitting the employer to have confidence (e.g., 95%) that if results from personal air samples are below the AL, the probability is small that worker exposures are above the REL. NIOSH has concluded that the use of an AL permits the employer to monitor hazardous workplace exposures without daily sampling. The AL concept has served as the basis for defining the elements of an occupational standard in NIOSH criteria documents and comprehensive standards promulgated by the Occupational Safety and Health Administration (OSHA) and the Mine Safety and Health Administration (MSHA).

# Hazard Communication
Employers shall take the following measures to inform workers about RCF hazards:
 Establish a safety and health training program for all workers who manufacture, use, handle, install, or remove RCF products or perform other activities that bring them into contact with RCFs.
 Inform employees and contract workers about hazardous substances in their work areas.
 Instruct workers about how to get information from material safety data sheets (MSDSs) for RCFs and other chemicals.
 Provide MSDSs onsite and make them easily accessible.
 Inform workers about adverse respiratory health effects associated with RCF exposures.
 In work involving the removal of refractory insulation materials, make workers aware of the potential for exposure to respirable crystalline silica, the health effects related to this exposure, and methods for reducing exposures.
 Make workers who smoke cigarettes or use other tobacco products aware of their increased risk of developing RCFinduced respiratory symptoms and conditions (see Sections 1.12 and 9.6 for recommendations about smoking cessation programs).

# Training
Employers shall provide the following training for workers exposed to RCFs:
 Train workers to detect hazardous situations.
 Inform workers about practices or operations that may generate high airborne fiber concentrations (e.g., cutting and sanding RCF boards and other RCF products).
 Train workers how to protect themselves by using proper work practices, engineering controls, and personal protective equipment (PPE).

# Product Formulation
One factor recognized as contributing to the toxicity of an inhaled fiber is its durability and resistance to degradation in the respiratory tract. Chemical characteristics place RCFs among the most durable SVFs. As a result, an 1  Recommendations for a Refractory Ceramic Fiber Standard inhaled RCF that is deposited in the alveolar region of the lung will persist longer in the lungs than a less durable fiber. Therefore, NIOSH recommends substituting a less durable fiber for RCFs or reformulating the chemistry of RCFs toward this end to reduce the hazard for exposed workers. As part of product stewardship efforts, several RCF producers within the Refractory Ceramic Fibers Coalition (RCFC) have developed new and less biopersistent fibers termed alkaline earth silicate wools . Newly developed fibers should undergo industry-sponsored testing before their selection and commercial use to exclude possible adverse health effects from exposure.

# Engineering Controls and Work Practices

# Engineering Controls
Employers shall use and maintain appropriate engineering controls to keep airborne concentrations of RCFs at or below the REL during the manufacture, use, handling, installation, and removal of RCF products. Engineering controls for controlling RCFs include the following:
 Local exhaust ventilation or dust collection systems at or near dust-generating systems -Band saws used in RCF manufacturing and finishing operations have been fitted with such engineering controls to capture fibers and dust during cutting operations, thereby reducing exposures for the band saw operator .
-Disc sanders fitted with similar local exhaust ventilation systems effectively reduce airborne RCF concentrations during the sanding of vacuum-formed RCF products .
 Enclosed processes used during manufacturing to keep airborne fibers contained and separated from workers  Water knives, which are high-pressure water jets that effectively cut and trim the edges of RCF blanket while suppressing dust and limiting the generation of airborne fibers

# Work Practices
Employers shall implement appropriate work practices to help keep worker exposures at or below the REL for RCFs. The following work practices are recommended to help reduce concentrations of airborne fibers:
 Limit the use of power tools unless they are equipped with local exhaust or dust collection systems.
-Be aware that manually powered hand tools generate less dust and fewer airborne fibers, but they often require additional physical effort and time and may increase the risk of musculoskeletal disorders.
-The additional physical effort required by hand tools may also increase the rate and depth of breathing and consequently affect the inhalation rate and deposition of fibers in the lungs.
 Use ergonomically correct tools and proper workstation design to reduce the risk of musculoskeletal disorders.
 Use high-efficiency particulate air-filtered (HEPA-filtered) vacuums.
 Use wet sweeping to suppress airborne fiber and dust concentrations during cleanup.
 When removing after-service RCF products, dampen insulation with a light water spray to prevent fibers and dust from becoming airborne. (However, use caution when dampening refractory linings during installation, since water can damage refractory-lined equipment, causing the generation of steam and possible explosion during heating.)
 Clean work areas regularly using a HEPAfiltered vacuum or wet sweeping to minimize accumulation of debris.
 Ensure that workers wear long-sleeved clothing, gloves, and eye protection when performing potentially dusty activities involving RCFs or RCF products. For some activities, disposable clothing or coveralls may be preferred.

# Respiratory Protection
Respirators shall be used while performing any task for which the exposure concentration is unknown or has been documented to be higher than the NIOSH REL of 0.5 f/cm 3 as a TWA. However, respirators shall not be used as the primary means of controlling worker exposures.
When possible, use other methods for minimizing worker exposures to RCFs:
 Product substitution  Engineering controls  Changes in work practices Use respirators when available engineering controls and work practices do not adequately control worker exposures below the REL for RCFs. NIOSH recognizes that controlling exposures to RCFs is a particular challenge during the finishing stages of RCF product manufacturing and during the installation and removal of refractory materials

# Respiratory Protection Program
When respiratory protection is needed, employers shall establish a comprehensive respiratory protection program as described in the OSHA respiratory protection standard . Elements of a respiratory protection program must be established and described in a written plan that is specific to the workplace. The plan must include the following elements: comply with the medical evaluation and cleaning, storing, and maintenance requirements of the standard  A designated program administrator who is qualified to administer the respiratory protection program
Employers shall update the written program as necessary to account for changes in the workplace that affect respirator use. In addition, employers are required to provide at no cost to workers all equipment, training, and medical evaluations required under the respiratory protection program.

# Respirator Selection
When conditions of exposure to airborne RCFs exceed the REL, proper respiratory protection shall be selected as follows:
 Select, at a minimum, a half-mask, airpurifying respirator equipped with a 100 series particulate filter. This respirator has an assigned protection factor (APF) of 10.
 Provide a higher level of protection and prevent facial or eye irritation from RCF exposure by using a full-facepiece, air-purifying respirator equipped with a 100-series filter; or use any powered, air-purifying respirator equipped with a tight-fitting facepiece (full-facepiece).
 Consider providing a supplied-air respirator with a full facepiece for workers who remove after-service RCF insulation (e.g., furnace insulation) and are therefore exposed to high and unpredictable concentrations of RCFs. These respirators provide a greater level of respiratory protection. Use them whenever the work task involves potentially high concentrations of airborne fibers.
 Always perform a comprehensive assessment of workplace exposures to determine the presence of other possible contaminants (such as silica) and to ensure that proper respiratory protection is used.
 Use only respirators approved by NIOSH and MSHA.

# Sanitation and Hygiene
Employers shall take the following measures to protect workers potentially exposed to RCFs:
 Do not permit smoking, eating, or drinking in areas where workers may contact RCFs.
 Provide showering and changing areas free from contamination where workers can store work clothes and change into street clothes before leaving the work site.
 Provide services for laundering work clothes so that workers do not take contaminated clothes home.
 Protect laundry workers handling RCFcontaminated clothes from airborne concentrations that are above the REL.
Workers shall take the following protective measures:
 Do not smoke, eat, or drink in areas potentially contaminated with RCFs.
 If fibers get on the skin, wash with warm water and mild soap.
 Apply skin-moisturizing cream or lotion as needed to avoid irritation caused by frequent washing.
 Wear long-sleeved clothing, gloves, and eye protection when performing potentially dusty activities involving RCFs.
 Vacuum this clothing with a HEPA-filtered vacuum before leaving the work area.
 Do not use compressed air to clean the work area or clothing and do not shake clothing to remove dust. These processes will create a greater respiratory hazard with airborne dust and fibers.
 Do not wear work clothes or protective equipment home. Change into clean clothes before leaving the work site.

# Medical Monitoring
Medical monitoring (in combination with resulting intervention strategies) represents secondary prevention and should not replace primary prevention efforts to control airborne fiber concentrations and worker exposures to RCFs. However, compliance with the REL for RCFs (0.5 f/cm 3 ) does not guarantee that all workers will be free from the risk of RCFinduced respiratory irritation or respiratory health effects. Therefore, medical monitoring is especially important, and employers shall establish a medical monitoring program as follows:
 Collect baseline data for all employees before they begin work with RCFs.
 Continue periodic medical screening throughout their lifetime.
 Use medical surveillance, which involves the aggregate collection and analysis of medical screening data, to identify occupations, activities, and work processes in need of additional primary prevention efforts.
 Include all workers potentially exposed to RCFs (in both manufacturing and end-use industries) in an occupational medical monitoring program.
 Provide workers with information about the purposes of medical monitoring, the health benefits of the program, and the procedures involved.
 Include the following workers (who could receive the greatest benefits from medical screening) in the medical monitoring program:
-Workers exposed to elevated fiber concentrations (e.g., all workers exposed to airborne fiber concentrations above the AL of 0.25 F/cm 3 , as described in Section 9.3)
-Workers in areas or in specific jobs and activities (regardless of airborne fiber concentration) in which one or more workers have symptoms or respiratory changes apparently related to RCF exposure -Workers who may have been previously exposed to asbestos or other recognized occupational respiratory hazards that place them at an increased risk of respiratory disease

# Elements of the Medical Monitoring Program
Include the following elements in a medical monitoring program for workers exposed to RCFs: (1) an initial medical examination, (2) periodic medical examinations at regularly scheduled intervals, (3) more frequent and detailed medical examinations as needed on the basis of the findings from these examinations, (4) worker training, (5) written reports of medical findings, (6) quality assurance, and (7) evaluation. These elements are described in the following subsections.

# Initial (baseline) examination
Perform an initial (baseline) examination as near as possible to the date of beginning employment (within 3 months) and include the following:  
 A
 A standardized occupational history questionnaire that gathers information about all past jobs with (1) special emphasis on those with potential exposure to dust and mineral fibers, (2) a description of all duties and potential exposures for each job, and (3) a description of all protective equipment the worker has used

# Periodic examinations
Administer periodic examinations (including a physical examination of the respiratory system and the skin, spirometric testing, a respiratory symptom update questionnaire, and an occupational history update questionnaire) at regular intervals determined by the medical monitoring program director. Determine the frequency of the periodic medical examinations according to the following guidelines:
 For workers with fewer than 10 years since first exposure to RCFs, conduct periodic examinations at least once every 5 years.
 For workers with 10 or more years since first exposure to RCFs, conduct periodic examinations at least once every 2 years.
A chest X-ray and spirometric testing are important on initial examination and may also be appropriate medical screening tests during periodic examinations for detecting respiratory system changes, especially in workers with more than 10 years since first exposure to RCFs. A qualified health care provider should consult with the worker to determine whether the benefits of periodic chest X-rays warrant the additional exposure to radiation.

# More frequent evaluations
Workers may need to undergo more frequent and detailed medical evaluations if the attending physician determines that he or she has any of the following indications:
 New or worsening respiratory symptoms or findings (e.g., chronic cough, difficult breathing, wheezing, reduced lung function, or radiographic indications of pleural plaques or fibrosis) Findings, test results, or diagnoses that have no bearing on the worker=s ability to work with RCFs shall not be included in the report to the employer. Safeguards to protect the confidentiality of the worker=s medical records shall be enforced in accordance with all applicable regulations and guidelines.

# Quality assurance
Employers shall do the following to ensure the effective implementation of a medical monitoring program:
 Ensure that workers follow the qualified health care provider's recommended exposure restrictions for RCFs and other workplace hazards.
 Ensure that workers use appropriate PPE if they are exposed to RCF concentrations above the REL.
 Encourage workers to participate in the medical monitoring program and to report any symptoms promptly to the program director.
 Provide any medical evaluations that are part of the medical monitoring program at no cost to the workers.
 When implementing job reassignments recommended by the medical program director, ensure that workers do not lose wages, benefits, or seniority.
 Ensure that the medical monitoring program director communicates regularly with the employer's safety and health personnel (e.g., industrial hygienists) to identify work areas that may require control measures to minimize exposures to workplace hazards.

# Evaluation
Employers shall evaluate their medical monitoring programs as follows:
 Periodically have standardized medical screening data aggregated and evaluated by an epidemiologist or other knowledgeable person to identify patterns of worker health that may be linked to work activities and practices requiring additional primary preventive efforts.
 Combine routine aggregate assessments of medical screening data with evaluations of exposure monitoring data to identify needed changes in work areas or exposure conditions.

# Labeling and Posting
Employers shall post warning labels and signs as follows:  Establish smoking cessation programs to inform workers about the increased hazards of cigarette smoking and exposure to RCFs.
 Provide assistance and encouragement for workers who want to quit smoking.
 Prohibit smoking in the workplace.
 Disseminate information about health promotion and the harmful effects of smoking.
 Offer smoking cessation programs to workers at no cost to participants.
 Encourage activities that promote physical fitness and other healthy lifestyle practices affecting respiratory and cardiovascular health (e.g., through training programs, employee assistance programs, and health education campaigns).
NIOSH recommends that all workers who smoke and are potentially exposed to RCFs participate in smoking cessation programs.

# RESPIRATORY PROTECTION REQUIRED IN THIS AREA
 Print all labels and warning signs in both English and the predominant language of workers who do not read English.
 Verbally inform workers about the hazards and instructions printed on the labels and signs if they are unable to read them.

# Smoking Cessation
NIOSH recognizes a synergistic effect between exposure to RCFs and cigarette smoking. This effect increases the risk of adverse respiratory health effects induced by RCFs. In studies of workers exposed to various airborne contaminants, combined exposures to smoking and airborne dust have been shown to contribute to the increased risk of occupational respiratory diseases, including chronic bronchitis, emphysema, and lung cancer .

# Background
In 1977, NIOSH reviewed health effects data on occupational exposure to fibrous glass and determined the principal adverse health effects to be skin, eye, and upper respiratory tract irritation as well as the potential for nonmalignant respiratory disease. At that time NIOSH recommended the following:
Occupational exposure to fibrous glass shall be controlled so that no worker is exposed at an airborne concentration greater than 3,000,000 fibers per cubic meter of air (3 fibers per cubic centimeter of air); . . . airborne concentrations determined as total fibrous glass shall be limited to a TWA of 5 milligrams per cubic meter of air .
NIOSH also stated that until more information became available, this recommendation should be applied to other MMMFs, also called SVFs. Since then, additional data have become available from studies in animals and humans exposed to RCFs. The purpose of this report is to review and evaluate these studies and other information about RCFs. In contrast, the crystalline structure of mineral fibers such as asbestos causes the fibers to fracture along the longitudinal plane under mechanical stresses, resulting in more fibers with the same length but smaller diameters. These differences in morphology and cleavage patterns suggest that work with SVFs is less likely to generate high concentrations of airborne fibers than work with asbestos for comparable operations, since large-diameter fibers settle out in the air faster than small-diameter fibers . During the manufacturing of RCFs, approximately 50% of product (by weight) is generated as fiber, and 50% is a byproduct made up of nonfibrous particulate material called shot. Selected physical characteristics of RCFs are presented in  . The addition of stabilizers and binders alters the properties of durability and heat resistance for RCFs. Generally, three types of RCFs are manufactured, and a fourth after-service fiber (often recognized in the literature) is distinguished according to its unique chemistry and morphology. Table 2-2 presents the chemistries of the four fiber types, numbered RCF1 through RCF4. RCF1 is a kaolin fiber; RCF2 is an alumina/silica/zirconia fiber; RCF3 is a high-purity (alumina/silica) fiber; and RCF4 is an after-service fiber, characterized by devitrification (i.e., formation of the silica polymorph cristobalite), which occurs during product use over an extended period of time at temperatures exceeding 1,050 to 1,100 o C (>1,900 o F). Another fiber subcategory is RCF1a, prepared from commercial RCFs using a less aggressive method than that used to prepare RCF1 for animal inhalation studies . RCF1a is distinguished from RCF1 used in chronic animal inhalation studies, the former having a greater concentration of longer fibers and fewer nonfibrous particles. The lower ratio of respirable nonfibrous particles to fibers in RCF1a compared with RCF1 has been shown to affect lung deposition and clearance in animal inhalation studies . Chapter 5 presents additional discussion of animal studies and test fiber characteristics.

# Chemical and Physical

# Properties of RCFs

# Fiber Dimensions
Fibers of biological importance are those that become airborne and have dimensions within inhalable, thoracic, and respirable size ranges. Thoracic-sized fibers (<3 to 3.5 m in diameter) and respirable-sized fibers (<1.3 m in diameter) with lengths up to 200 m  are capable of reaching the portion of the respiratory system below the larynx. Respirablesized fibers are of biological concern because they are capable of reaching the lower airways and gas exchange regions of the lungs when inhaled. Longer or thicker airborne fibers generally settle out of suspension or, if inhaled, are generally filtered out in the nasal passage or deposited in the upper airways. Thoracic-sized fibers that are inhaled and deposited in the upper respiratory tract are generally cleared more readily from the lung, but they have the potential to cause irritation and produce respiratory symptoms. Fiber dimensions are a significant factor in determining their deposition within the lung, biopersistence, and toxicity.
RCFs and other SVFs are manufactured to meet specified nominal diameters according to the fiber type and intended use. RCFs are produced with nominal diameters of 1.2 to 3 m . Typical diameters for an individual RCF (as measured in   Mast et al. .
RCF-containing products) range from 0.1 to 20 m, with lengths ranging from 5 to 200 m . In bulk samples taken from three RCF blanket insulation products, more than 80% of the fibers counted by phase contrast optical microscopy (PCM) were <3 m in diameter . This result is consistent with those from another study of bulk samples of RCF insulation materials , which found the fibers to have geometric mean diameters (GM D ) ranging from 1.5 to 2.8 m (arithmetic mean  diameter range=2.3 to 3.9 m; median diameter range=1.6 to 3.3 m).
Studies of airborne fiber size distributions in RCF manufacturing operations indicate that these fibers meet the criteria for thoracic-and respirable-sized fibers. One early study of three domestic RCF production facilities found that approximately 90% of airborne fibers were 20 m, with 68% of fibers measuring 2.4 to 20 m long and 19% of the fibers >20 m long. On the basis of the results of TEM analysis of 3,357 RCFs observed on 98 air samples collected in RCF manufacturing sites, Allshouse  re-ported that 99.7% of the fibers had diameters 10 m. Measurements of airborne fibers in the European RCF manufacturing industry are comparable : Rood  reported that all fibers observed were in the thoracic and respirable size range (i.e., diameter <3 to 3.5 m), with median diameters ranging from 0.5 to 1.0 m and median lengths from 8 to 23 m. Cheng et al.  analyzed an air sample for fibers during removal of after-service RCF blanket insulation from a refinery furnace. Fiber diameters ranged from 0.5 to 6 m, with a median diameter of 1.6 m. The length of fibers ranged from 5 to 220 m. Of 100 fibers randomly selected and analyzed from the air sample, 87% were within the thoracic and respirable size range. Another study of exposures to airborne fibers in industrial furnaces during installation and removal of RCF materials found GM D values of 0.38 and 0.57 m, respectively .

# Fiber Durability
Fiber durability can affect the biologic activity of fibers inhaled and deposited in the respiratory system. Durable fibers are more biopersistent, thereby increasing the potential for causing a biological effect. Durability of a fiber is measured by the amount of time it takes for the fiber to fragment mechanically into shorter fibers or dissolve in biological fluids. RCFs tested in vitro with a solution of neutral pH (modified Gamble's solution) had a dissolution rate of 1 to 10 ng/cm 2 per hr . This test is biologically relevant because of the similarity of the solution to the conditions of the pulmonary interstitial fluid. By comparison, other SVFs (glass and slag wools) are more soluble, with dissolution rates in the 100s of ng/cm 2 per hr . Along a continuum of fiber durability determined in tests using simulated lung fluids at pH 7.4, the asbestos fiber crocidolite has a dissolution rate of <1 ng/cm 2 per hr, RCF1 and MMVF32 (E glass) have dissolution rates of 1 to 10 ng/cm 2 per hr, MMVF21 has a dissolution rate of 15 to 25 ng/cm 2 per hr, other fibrous glass and slag wools have dissolution rates in the range of 50 to 400 ng/cm 2 per hr, and the alkaline earth silicate wools have dissolution rates ranging from approximately 60 to 1,000 ng/cm 2 per hr .
Chrysotile, which is considered the most soluble form of asbestos, has a dissolution rate of <1 to 2 ng/cm 2 per hr.
RCFs dissolve more rapidly than chrysotile, even though RCFs have a thicker diameter (by an order of magnitude) than chrysotile. The rate of dissolution is an important fiber characteristic that affects the clearance time and biopersistence of the fiber in the lung. The significance of fiber dimension, clearance, and dissolution (i.e., breakage, solubility) is discussed in Chapter 6.

# RCF Production and Potential for
Worker Exposure

# Production
RCF production in the United States began in 1942 on an experimental basis, but RCFs were not commercially available until 1953. Sales of RCFs were modest initially, but they began to expand when the material gained acceptance as an economical alternative insulation for high-temperature kilns and furnaces. Commercial production of RCFs first reached significant levels in the 1970s as oil shortages necessitated reductions in energy consumption. The growing demand for RCFs has also been strongly influenced by the recognition of health effects associated with exposure to asbestos-containing materials and the increasingly stringent regulation of these products in the United States and many other countries.

# Potential for Worker Exposure
Approximately 31,500 workers in the United States are potentially exposed to RCFs during manufacturing, processing, or end use. A similar number of workers are potentially exposed to RCFs in Europe. Of these workers, about 800 (3%) are employed in the actual manufacturing of RCFs and RCF products .

# RCF Manufacturing Process
The manufacture of RCFs (Figure 3-1) begins by blending raw materials, which may include kaolin clay, alumina, silica, and zirconia in a batch house. The batch mix is then transferred either manually or automatically to a furnace to be melted at temperatures exceeding 1,600 o C. On reaching a specified temperature and viscosity in the furnace, the molten

#  RCF Production and Potential for Worker Exposure
Fibers are produced by blowing or spinning molten materials drained from furnace.
Bulk fiber is packaged.
Felt or blanket is cured in tempering oven.
Product is shipped, stored, or fabricated into specialty product. batch mixture drains from the furnace and is fiberized, either through exposure to pressurized air or by flowing through a series of spinning wheels . Fans are used to create a partial vacuum that pulls the fibers into a collection or settling chamber. RCFs may then be conveyed pneumatically to a bagging area for packaging as bulk fiber. Some bulk fiber may be used directly in this form, or it may be processed to form textiles, felts, boards, cements, and other specialty items. Other RCFs are formed into blankets as bulk fiber in the collection chamber settles onto a conveyor belt. The blanket passes through a needle felting machine that interlocks the fibers and compresses the blanket to a specified thickness. From the needler, the blanket is conveyed to a tempering oven to remove lubricants that were added in the settling chamber. The lubricants are burned off, and the blanket is cut to desired size and packaged. As with the bulk fiber, the RCF blanket may undergo additional fabrication to create other specialty products. Many of the processes are automated and are monitored by machine operators. Postproduction processes such as cutting, sanding, packaging, handling, and shipping are more labor intensive, but the potential exists for exposure to airborne fibers throughout production.

# RCF Products and Uses
RCFs may be used in bulk fiber form or as one of the RCF specialty products in the form of mats, paper, textiles, felts, and boards . Because of its ability to withstand temperatures exceeding 1,000 C, RCFs are used predominantly in industrial applications, including insulation, reinforcement, and thermal protection for furnaces and kilns. RCFs can also be found in automobile catalytic converters, in consumer products that operate at high temperatures (e.g., toasters, ovens, woodstoves), and in space shuttle tiles. RCFs have been formed into noise-control blankets  and used as a replacement for refractory bricks in industrial kilns and furnaces . RCFs have found increasing application as reinforcements in specialized metal matrix composites (MMC), especially in the automotive and aerospace industries . A summary of RCF products and applications are provided here.

# Examples of Products
 Blankets-high-temperature insulation produced from spun RCFs in the form of a mat or blanket  Boards-high-temperature insulation produced from bulk fibers in the form of a compressed rigid board (boards have a higher density than blankets and are used as core material or in sandwich assemblies)
 Bulk RCFs-fibers with qualities of hightemperature resistance to be used as feedstock in manufacturing processes or other applications for which product consistency is critical-typically in the manufacture of other ceramic-fiber-based products The conventional method used to assess the characteristics and concentrations of exposures to airborne fibers is to collect personal and environmental (area) air samples for laboratory analysis.
Personal samples are the preferred method for estimating the exposure characteristics of a worker performing specific tasks. For personal sampling, a worker is equipped with the air sampling equipment, and the collection medium is positioned within the worker's breathing zone. Area sampling is performed to evaluate exposure characteristics associated with an area or process. Sampling equipment for area sampling is stationary, in contrast to personal sampling, which allows for mobility by accompanying the worker throughout the sampling period.

# Sampling for Airborne Fibers
The two NIOSH methods for the sampling and analysis of airborne fibers of asbestos and other fibrous materials are as follows:
 Method 7400 describes air sampling and analysis by PCM  Method 7402 describes air sampling and analysis by TEM Both methods (listed in the NIOSH Manual of Analytical Methods  and provided in Appendix A) involve using an air sampling pump connected to a cassette. The cassette consists of a conductive cowl equipped with a 25-mm cellulose ester membrane filter (0.45-to 1.2-m pore size). The pump is used to draw air through the sampling cassette at a constant flow rate between 0.5 and 16 L/min. Airborne fibers and other particulates are trapped on the filter for analysis using microscopic methods. Methods 7400 and 7402 can be used to count the number of fibers (and therefore calculate concentration based on the volume of air sampled) and measure the fiber dimensions. Fiber concentration is reported as the number of fibers per cubic centimeter of air (f/cm 3 ). Although the two methods differ in preparation of the sampling media for analysis, the major distinction between them is the resolving capabilities of the microscope. With PCM, 0.25 m is approximately the diameter of the thinnest fibers that can be observed . TEM has a lower resolution limit well below the diameter of the smallest RCF (~0.02 to 0.05 m) . TEM also allows for qualitative analysis of fibers using an energy-dispersive X-ray analyzer (EDXA) to determine elemental composition and selected area electron diffraction (SAED) for comparing diffraction patterns with reference patterns for identification.

# NIOSH Fiber-Counting Rules
The appendix to NIOSH Method 7400 specifies two sets of fiber-counting rules that vary according to the parameters used to define a fiber. Under the A rules, any particle >5 m long with an aspect ratio (length to width) >3:1 is considered a fiber. No upper limit exists on the fiber diameter in the A counting rules. In the B rules, a fiber is defined as being >5 m long with an aspect ratio 5:1 and a diameter 3:1 aspect ratio also meet the 5:1 aspect ratio criterion and are <3 m in diameter.

# Sampling for Total or Respirable Airborne Particulates
Airborne exposures generated during work with RCFs may also be estimated by sampling for general dust concentrations. Sampling for particulates not otherwise regulated is described in NIOSH Method 0500 for total dust concentrations and in NIOSH Method 0600 for the respirable fraction . Both methods (also included in Appendix A) use a sampling pump to pull air through a filter that traps suspended particulates. NIOSH Method 0600 uses a size-selective sampling apparatus (cyclone) to separate the respirable fraction of airborne material from the nonrespirable fraction. The mass of airborne particulates on the filter is measured using gravimetric analysis, and airborne concentration is determined as the ratio of the particulate mass to the volume of air sampled, reported as mg/m 3 (or g/m 3 ). This method does not distinguish fibers from nonfibrous airborne particles. No NIOSH REL exists for either total or respirable particulates not otherwise regulated. The OSHA permissible exposure limit (PEL) for particulates not otherwise regulated is 15 mg/m 3 for total particulates and 5 mg/m 3 for respirable particulates as 8-hr TWA concentrations. The American Conference of Governmental Industrial Hygienists (ACGIH) threshold limit value (TLV) for particles (insoluble or poorly soluble) not otherwise specified is 10 mg/m 3 for inhalable particles and 3 mg/m 3 for respirable particles as 8-hr TWA concentrations .

# Sampling for Airborne Silica
Because silica is a major constituent of RCFs, the potential exists for exposure to silica during work with RCFs (e.g., in manufacturing or during removal of after-service RCF furnace insulation). As with sampling for respirable particulates, sampling for respirable silica involves using a pump to draw air through a cyclone before collecting respirable airborne particles on a filter. Qualitative and quantitative analysis of the sample for silica content can be performed using the following analytical methods:
 X-

# Industrial Hygiene Surveys and Exposure Assessments
Assessments of occupational exposures, including quantitative measurement of airborne fiber concentrations associated with manufacturing, handling, and using RCFs, have been performed using industrial hygiene surveys and air sampling techniques at multiple worksites. Sources of monitoring data that characterize occupational exposures to RCFs include the following:
 University of Pittsburgh studies of exposures at RCF manufacturing sites in the 1970s   International (Canadian, Swedish, Australian) industrial hygiene surveys of occupational exposures to RCFs   A study of end-user exposures to RCF insulation products by researchers at Johns Hopkins University   NIOSH Health Hazard Evaluations (HHEs) of occupational exposures to RCFs

# University of Pittsburgh Survey of Exposures During RCF Manufacturing
In the mid 1970s, researchers from the University of Pittsburgh conducted environmental monitoring to assess worker exposures to airborne fibers at domestic RCF manufacturing facilities. This research effort was one of the pioneering studies in the use of workplace exposure groupings or dust zones for establishing a sampling strategy .
In a series of industrial hygiene surveys, Esmen et al.  collected 215 full-shift air samples at three RCF manufacturing plants. of the airborne fibers measured were <4.0 m in diameter and <50 m long with a GM D of 0.7 m and a GM L of 13 m.

# University of Cincinnati Study of Exposures During RCF Manufacturing
In 1987, researchers from the University of Cincinnati initiated an industry-wide epidemiologic study of workers who manufacture RCFs.
One aim of the study was to characterize current and former exposures to RCFs and silica in U.S. RCF manufacturing facilities. Data from initial surveys conducted at five RCF manufacturing plants indicated airborne RCFs with a GM D ranging from 0.25 to 0.6 m and a GM L ranging from 3.8 to 11.0 m . The airborne TWA fiber concentrations for these five plants ranged from <0.01 to 1.57 f/cm 3 . After the first two rounds of quarterly sampling, Rice et al.  had collected data from 484 fiber count samples (382 samples with values greater than the analytic limit of detection , 39 overloaded samples, 36 samples with values below the LOD, and 27 samples voided because of tampering or pump failure). They also collected 35 samples from persons working with raw materials that were analyzed quantitatively and qualitatively for respirable mass and for silica polymorphs (quartz, tridymite, and cristobalite). A sampling strategy was developed by identifying more than 100 job functions across 5 facilities. These job functions were consolidated into industry job titles based on similarities of function, proximity to certain processes, and exposure characteristics within designated dust zones.  nett et al. 1989;Breysse et al. 1990], ranged from below the analytical LOD to 1.54 f/cm 3 . Of the 35 samples analyzed for the silica polymorphs, quantifiable silica was found in 5 samples: 4 of the samples contained cristobalite in concentrations ranging from 20 to 78 g/m 3 , and 1 of the samples contained 70 g/m 3 quartz. The measurable silica exposures occurred among workers employed as raw material handlers and furnace operators.
As the study progressed, approximately 1,820 work history interviews were conducted and evaluated to refine uniform job titles and to identify dust zones according to the method of Corn and Esmen . Four years of sampling data (1987)(1988)(1989)(1990)(1991) were merged with historic sampling data to construct exposure estimates for 81 job titles in 7 facilities for specified time periods . Overall exposures decreased. The maximum exposure estimated was 10 f/cm 3 in the 1950s for carding in a textile operation; subsequent changes in engineering, process, and ventilation reduced exposure estimates for all 20 job titles to near or below 1 f/cm 3 . The study reported that at more recent operations (1987)(1988)(1989)(1990)(1991), exposure estimates ranged from below the analytic LOD to 0.66 f/cm 3 .
Subsequently, Rice et al.  published the results from an analysis of exposure estimates for 10 years of follow-up sampling (19912001)  The study shows that exposures decreased for 25% of job titles, remained stable for 53%, and increased for 22%. Of the job titles with increased exposure estimates, 9 estimates were >0.1 f/cm 3 (range = 0.1 to 0.21 f/cm 3 ), and 19 estimates were <0.1 f/cm 3 . The exposure estimates for this study do not include adjustments for respirator use.

# RCFC/EPA Consent Agreement Monitoring Data
In 1993, the RCFC and the EPA entered into a negotiated 5-year consent agreement to determine the magnitude of RCF exposures in the primary RCF manufacturing industry and in secondary RCF-use industries . Another purpose of this consent agreement was to document changes in RCF exposures during the 5 years of the agreement (1993)(1994)(1995)(1996)(1997)(1998). The Quality Assurance Project Plan in the consent agreement contains the analytical protocols, statistical design, description of the program objectives, and timetables for meeting the objectives .
During each year of the consent agreement, a minimum of 720 personal air samples (measured as 8-hr TWAs) were collected according to a stratified random sampling plan. Of these, 320 samples were collected in RCF manufacturing and processing (primary) facilities. The remaining 400 samples were collected in RCF  Fibers were defined as having an aspect ratio of 5:1 and length >0.5 m if sized using transmission electron micoscopy. For scanning electron microscopy, fibers were defined with the same aspect ratio and length >5 m. I Fore is the area of the plant before the furnace. customer facilities referred to as end-use (secondary) facilities. The researchers collected a total of 4,576 samples. A number of end-use facilities were randomly selected from a list of known purchasers of RCF products. The remainder consisted of facilities that volunteered for sampling once they learned of the consent agreement. The strata from which the 720 samples were collected consist of eight functional job categories derived so that results could be aggregated for comparison across industries, facilities, and similar job functions . This categorization was based on the approach instituted by Corn and Esmen . Appendix B lists definitions and major work tasks for each functional job category. TWA and task-length average air sampling data were gathered according to NIOSH Method 7400 (B rules) and analyzed using PCM and TEM. Data on respirator use (by type) were also collected .
As background for the consent agreement monitoring plan, baseline (now referred to as historical) information about airborne fiber concentrations was obtained through personal sampling of workers at RCF manufacturing facilities from January 1989 to May 1993. Exposure monitoring strategies used during the baseline period (1989)(1990)(1991)(1992)(1993) provided the framework for the consent agreement (1993)(1994)(1995)(1996)(1997)(1998) monitoring protocol.  (1989)(1990)(1991)(1992)(1993) and consent agreement monitoring (1993)(1994)(1995)(1996)(1997)(1998) periods by manufacturing and end-use sectors.
A comparison of values from Tables 4-4, 4-5, and 4-6 with those in Table 4-3 indicates that average airborne concentrations for 1993-1998 were lower than those for the preceding baseline sampling period (1989)(1990)(1991)(1992)(1993). However, a comparison of values in Tables 4-5 and 4-6 shows that average concentrations for the entire 5-year consent agreement monitoring period (1993)(1994)(1995)(1996)(1997)(1998) are equal to those of year 5 (i.e., no change).
After the first 3 years (1993)(1994)(1995)(1996) of the consent agreement monitoring period, Maxim et al.  performed interim analyses of these data combined with historical data from the baseline monitoring period (1989)(1990)(1991)(1992)(1993). The following conclusions about RCF exposures were based on these analyses of data from 1,600 baseline samples and 3,200 consent agreement samples:  Airborne concentrations of RCFs are generally decreasing in the workplace.
 Ninety percent of airborne concentrations of RCFs in the workplace are below 1 f/cm 3 .
 RCF concentrations have an approximately log-normal distribution.
 Significant differences exist in workplace concentrations by facility.
 Workplace concentrations vary with functional job category.
 Respirator usage varies with the worker's functional job category and the associated average fiber concentration.
 Workplace samples have a lower ratio of respirable nonfibrous particles to fibers than samples used in initial animal inhalation studies .
Functional job categories with the highest average TWA fiber concentrations include removal (AM=1.2 f/cm 3 ), finishing (AM=0.8 f/cm 3 ), and  installation (AM=0.4 f/cm 3 ). The remainder of the functional job categories had average TWA concentrations near or below 0.3 f/cm 3 . Although different jobs and activities are associated with the three higher exposure functional job categories, similarities exist that contribute to exposure concentrations. First, removal and installation activities are performed at remote jobsites where implementing fixed engineering controls may be difficult or impractical for reducing airborne fiber concentrations. Removal requires more mechanical energy and may involve fracturing the structure of the RCF product, resulting in fiber release and higher concentrations of airborne fibers. Finishing activities are performed at fixed locations where it is possible to implement engineering controls, but they also involve mechanical energy to shape RCF products by drilling, sanding, and sawing. These processes also result in the dispersal of airborne fibers.
Regarding particle-to-fiber ratio, Maxim et al.  found average workplace values to be much lower (0.53; n=10; range not reported) than the average ratio (9.1; n=7) in the samples used in a series of animal inhalation toxicity studies with RCFs .
Monitoring performed during the baseline period (August 1989-May 1993 and the 5-year consent agreement period (June 1993-May 1998) provided data from nearly 6,200 air samples in the domestic RCF industry. Table 4-6 presents the summary statistics of workplace RCF exposure concentrations for the baseline (historical) and consent agreement monitoring data. The data suggest that (1) the AMs and GMs of RCF concentrations were higher for workers during the baseline period than during the more recent (consent monitoring data) period, and (2) AM and GM exposure concentrations were lower for workers in manufacturing facilities than at end-use sites.

# Exposures During Installation and Removal of RCF Furnace Insulation
To evaluate exposures to airborne dust associated with removing RCF furnace insulation, Gantner  conducted surveys with air sampling at five sites. The surveys were performed at sites where workers removed modules or blanket-type insulation manually using knives or trowels. During removal activities, workers wore disposable, single-use respirators, disposable protective clothing or their own personal clothing, and (in some cases) goggles or other protective eyewear. Personal sampling was performed for total dust concentration as well as respirable dust concentration using a cyclone. Area samples were collected in the center of work zones (industrial furnaces) at 9 ft above the floor, which was at the breathing zone level of the workers, who were on scaffolding. A total of 24 air samples were collected, including 14 personal samples (9 for respirable dust and 5 for total dust concentrations) and 10 area samples (3 for respirable dust and 7 for total dust concentrations).   Cheng et al.  studied exposures to RCFs during the installation and removal of RCF insulation in 13 furnaces at 6 refineries and 2 chemical plants. Air samples were collected and analyzed according to NIOSH Method 7400 (A rules); sampling times ranged from 15 to 300 min. Samples collected during minor maintenance and inspection tasks (n=27) showed GM concentrations of 0.08 to 0.39 f/cm 3 (range=0.02 to 17 f/cm 3 ). Sampling performed during installation of RCF insulation (n=59) revealed GM concentrations of 0.14 to 0.62 f/cm 3 (range=0.02 to 2.6 f/cm 3 ). The highest exposures were observed in samples collected during removal of RCF insulation (n=32), with GM concentrations of 0.02 to 1.3 f/cm 3 (range=<0.01 to 17 f/cm 3 ). Workers working outside of enclosed spaces (furnaces) were rarely exposed to more than 0.2 f/cm 3 . One sample of after-service RCF insulation was analyzed for fiber diameter and length: median diameter was reported as 1.6 m (range=0.5 to 6 m), and length ranged from 5 to 220 m. Of 100 fibers randomly selected and analyzed from the air sample, 87% were within the respirable size range. Four personal samples were collected during removal of after-service RCF modules and fire bricks and were analyzed for respirable crystalline silica (cristobalite). Samples revealed concentrations ranging from 0.03 mg/m 3 to 0.2 mg/m 3 (GM=0.06 mg/m 3 ).
At a Dutch oil refinery, van den Bergen et al.  performed personal air monitoring for airborne fibers to assess worker exposures during the removal of RCF insulation from expansion seams in a heat-treating furnace. The 8-hr TWA exposures for 5 workers sampled ranged from 9 to 50 f/cm 3 (GM=16 f/cm 3 ). Sweeney and Gilgrist  also monitored worker exposures to airborne RCFs and respirable silica during the removal of RCF materials from furnaces. Personal samples from two workers taken during the removal of after-service RCF insulation revealed exposures of 0.15 and 0.16 f/cm 3 . Exposures to total particulate (18.3 and 22.4 mg/m 3 as 8-hr TWAs) were above the OSHA PEL of 15 mg/m 3 . Exposure concentrations for respirable dust containing crystalline silica (2.4% and 4.3%) were also above the OSHA PEL. The elevated concentrations of respirable and total dust were associated with removal of conventional refractory lining using jackhammers, crowbars, and hammers. A worker performing routing to install new RCF insulation was exposed at 1.29 f/cm 3 (8-hr TWA). Personal samples from another worker using a bandsaw to cut new RCF insulation revealed concentrations of 1.02 f/cm 3 as an 8-hr TWA.
In the RCF industry, worker exposures to respirable crystalline silica (including quartz, cristobalite, and tridymite) may occur during the use of silica in manufacturing, removal of after-service insulation, and waste disposal. Focusing on exposures of workers who install, use, or remove RCF insulation, Maxim et al.  collected 158 personal air samples analyzed for respirable quartz, cristobalite, and tridymite over the RCFC/EPA 5-year consent agreement monitoring period (1993)(1994)(1995)(1996)(1997)(1998). A total of 42 removal projects were sampled. For small jobs, all workers engaged in insulation removal were sampled; for larger jobs, workers were selected at random for sampling. Air sampling and analysis were performed according to NIOSH Method 7500 for crystalline silica by X-ray diffraction; sampling times ranged from 37 to 588 min (AM=260 min, standard deviation =129 min). Short sampling times reflected the short duration of RCF insulation removal tasks (a benefit over time-intensive removal of conventional refractories). Removal of RCF blankets and modules is performed by using knives, pitchforks, rakes, and water lances, or by hand-peeling. The study noted that most (>90%) workers wear respirators (with protection factors from 10 to 50 or more) when removing insulation. Analysis of 158 samples found the following:  Fourteen samples had task-time respirable quartz concentrations ranging from 0.01 to 0.44 mg/m 3 (equivalent 8-hr TWA range=0.004 to 0.148 mg/m 3 ); the remainder of samples were below the LOD.
 Three samples had detectable concentrations of cristobalite that were below the NIOSH REL of 0.05 mg/m 3 .
 One sample contained tridymite (0.2 mg/m 3 ) at a concentration exceeding the NIOSH REL of 0.05 mg/m 3 .

# International (Canadian, Swedish, and Australian) Surveys of RCF Exposure
Perrault et al.  reported on the characteristics of fiber exposures that occurred during the use of synthetic fiber insulation materials on construction sites in Canada. Fiber dimensions were measured from bulk samples of insulation materials used at five construction sites. Area air samples were also collected during the installation of composite RCF and glass wool insulation, glass wool alone, rock wool (both blown and sprayed on), and RCFs alone.
Respirable fiber concentrations were highest during removal and installation of RCFs (0.39 to 3.51 f/cm 3 ) compared with concentrations measured during installation of rock wool (0.15 to 0.32 f/cm 3 ), composite RCF and glass wool (0.04 f/cm 3 ), and glass wool alone (0.01 f/cm 3 ). Diameters of fibers in bulk samples differed significantly from diameters in airborne fibers. RCFs had the smallest GM D of fibers in bulk samples (0.38 to 0.55 m) compared with glass wool (0.93 m) and rock wool (1.1 to 3.9 m). For airborne fibers, rock wool (sprayed on) had a GM D of 2.0 m, followed by RCFs (1.1 m), composite RCFs and glass wool (0.71 m), glass wool (0.5 m) and blown rock wool (0.5 m). Elemental analysis and comparison of bulk samples with air samples revealed a greater concentration of fibers with oxides of silicon and aluminum in air samples. For sites with either glass wool or rock wool insulation, airborne samples contained fewer fibers with silicon oxide as the sole constituent than bulk samples. The authors concluded that airborne fiber concentrations were affected by the type of fiber material used and the confinement of worksites. The authors also concluded that characterization of fibers in bulk samples is not a good representation of physical and chemical parameters of the airborne fibers.
A report by the Swedish National Institute for Occupational Health  describes exposure to RCFs in smelters and foundries based on industrial hygiene surveys and sampling at 4 facilities: a specialty steel foundry (2,500 workers), a metal smelting plant (1,500 workers), an aluminum foundry (450 workers), and an iron foundry (450 workers). RCF products were used in these plants in ladles, tapping spouts, holding furnaces, heat treatment furnaces, and spill protection mats. Workers and contractors were placed into three exposure categories, depending on their potential for exposure (as determined by distance from a fiber source). The highest exposures to airborne ceramic fibers (category 1) had median concentrations of 0.26 to 1.2 f/cm 3 and involved about 3% (n=160) of the workers at the plants surveyed. Secondary exposures (categories 2 and 3) involved another 33% (n=1,650) of the workers and had median concentrations of 0.03 to 0.24 f/cm 3 . During certain operations such as removal or demolition of RCF materials in enclosed spaces, concentrations of up to 210 f/cm 3 were measured. Total dust concentrations increased with fiber concentration and were as high as 600 mg/m 3 during demolition and 60 mg/m 3 during reinsulation. Median fiber diameters from bulk samples analyzed by electron microscopy ranged from 0.6 to 1.5 m, which was comparable to the diameters of airborne fibers. On the basis of air sampling data, fiber dose (assuming a working lifetime of 40 years ) was estimated for 8 occupations with category 1 exposures. Dose estimates ranged from 0.05 fiber-years/cm 3 for a cleaner to 85 fiber-years/cm 3 for a bricklayer or contractor. Dose estimates for the 6 other occupations ranged from 0.6 fiber-years/cm 3 to 3.1 fiber-years/cm 3 .
Researchers at the Australian National Occupational Health and Safety Commission established a technical working group to investigate typical exposures in SVF manufacturing and user industries . The RCF manufacturing industry is relatively small in Australia: 2 plants employing roughly 40 workers have been manufacturing RCFs since 1976 and 1977. Since the plants began manufacturing RCFs, 152 persons have been involved with production. Airborne fiber concentrations in both plants decreased over time as a result of (1) the introduction of a national exposure standard of 0.5 f/cm 3 for synthetic fibers and a secondary standard of 2 mg/m 3 for inspirable dust, (2) the use of various controls and handling technologies, and (3) increased awareness of dust suppression by the workforce. GM concentrations of airborne fibers before implementation of the synthetic fiber exposure standard (1983-1990) measured 0.52 f/cm 3 (geometric standard deviation =3.9) and 0.29 f/cm 3 (GSD=2.5) for plants 1 and 2, respectively. GM concentrations for the subsequent period (1991)(1992)(1993)(1994)(1995)(1996) dropped to 0.11 f/cm 3 (GSD=4.1) at plant 1 and 0.27 f/cm 3 (GSD=3.3) at plant 2.

# Johns Hopkins University Industrial Hygiene Surveys
A report of RCF end-user exposure data prepared for the Thermal Insulation Manufacturers Association (TIMA) showed that using blanket, bulk, and vacuum-formed RCFs during certain operations resulted in high fiber concentrations . For example, 25 personal air samples collected from workers installing RCF blanket modules had an AM, 8-hr TWA concentration of 1.36 f/cm 3 (SD=1.15). The fibers were collected and analyzed using NIOSH Method 7400 (B rules).
Seventeen vacuum formers had AM exposure concentrations of 0.71 f/cm 3 (SD=0.83) while using bulk RCF products. Twenty-eight workers with the job title vacuum-formed RCF cast finisher had AM exposures of 1.55 f/cm 3 (SD=1.51). Table 4-7 summarizes exposure data collected for the 17 occupations sampled during the study. Scanning electron microscopy (SEM) was used to measure dimensions of approximately 3,500 fibers from selected air samples of the 17 occupations. GM fiber diameters ranged from 0.9 to 1.5 m, and GM fiber lengths ranged from 20.4 to 36.1 m. Fiber aspect ratios based on these data ranged between 16:1 and 30:1.

# NIOSH HHEs and Additional Sources of RCF Exposure Data
NIOSH has conducted HHEs involving potential exposures to RCFs at the following work places: an RCF manufacturing facility , a steel foundry , a power plant , a foundry , and a railroad car wheel and axle production facility .

# Discussion
Recent and historical environmental monitoring data  indicate that airborne concentrations of RCFs include fibers in the thoracic and respirable size range (<3.5 m in diameter and <200 m long ). Workers are exposed to these concentrations during primary RCF manufacturing, secondary manufacturing or processing, and end-use activities such as RCF installation and removal. Sampling data from studies of domestic primary RCF manufacturing sites indicate that average airborne fiber concentrations have steadily declined by nearly 2 orders of magnitude over the past 2 decades. Rice et al.  report an estimated maximum airborne concentration of 10 f/cm 3 associated with an RCF manufacturing process in the 1950s. Esmen et al.  recognized average exposure concentrations ranging from 0.05 to 2.6 f/cm 3 in RCF manufacturing facilities in the mid-to late-1970s. During the late 1980s, Rice et al.  calculated average airborne concentrations in manufacturing facilities that ranged from <LOD to 0.66 f/cm 3 . Maxim et al. [1994Maxim et al. [ , 1997Maxim et al. [ , 2000a report that from the late 1980s through 1997, concentrations ranged from an AM of <0.3 to 0.6 f/cm 3 (GM0.2 f/cm 3 ).
For many RCF manufacturing processes, reductions in exposure concentrations have been realized through improved ventilation, engineering or process changes, and product stewardship programs . Several functional job categories continue to be associated with fiber concentrations that exceed the average; these include finishing operations during manufacturing, removal operations, and installation performed by end users. Activities in these three categories require additional mechanical energy in handling RCF products (e.g., sawing, drilling, cutting, sanding), which increases the generation of airborne fibers. Removal and installation activities are performed at remote sites where conventional engineering strategies and fixed controls are more difficult to implement. For certain operations in which airborne fiber concentrations are greater (such as removal of RCF products from furnaces), jobs are performed for short periods and almost universally with the use of respiratory protection .
One additional consideration during work involving RCF exposure is the potential for exposure to respirable silica in the forms of quartz, tridymite, and cristobalite. Although the potential for such exposure exists in primary manufacturing (because silica is a major component of RCFs), monitoring data indicate that these exposures are generally low . Maxim et al.  reported that many airborne silica samples collected to assess exposures during installation and removal of RCF products contain concentrations below the LOD, with average concentrations of respirable silica ranging from 0.01 to 0.44 mg/m 3 (equivalent 8-hr TWA range=0.004 to 0.148 mg/m 3 ). Other studies indicate a greater potential for exposure to respirable silica (especially in the form of cristobalite) during removal of after-service RCF materials .
Processes associated with high concentrations of airborne fibers generally generate high concentrations of total and respirable dust as well .

# Effects of Exposure
Animal studies report the concentration(s) to which the animals were exposed. The distinction between administered exposure concentration and received dose is important when analyzing these studies. The dose affecting the target tissues is known only when the amount of fiber present in the lung is measured and reported. To analyze the results of RCF studies, the number of fibers per exposure, their dimensions, durabilities, and the delivered dose should be considered for making comparisons and conclusions regarding potential and relative toxicity.

# Intrapleural, Intraperitoneal, and Intratracheal Studies
Instillation and implantation studies deliver fibers directly to the trachea, pleural cavity, or peritoneal cavity, bypassing some of the defense and clearance mechanisms that act on inhaled fibers. Implantation of fibers into either the pleural or abdominal cavities delivers fibers directly to the pleural or abdominal mesothelium, bypassing some or all of the normal defense and clearance mechanisms of the respiratory tract.
Intratracheal instillation delivers fibers directly to the trachea, bypassing the upper respiratory tract. These exposure methods do not mimic an occupational inhalation exposure of several hours per day for several days per week over an extended period. However, one advantage of these studies is that they allow the administration of a precise dose of fibers that can be replicated between animals. They also permit the administration of higher doses than may be obtainable by inhalation exposure.

# Health Effects in Animals (In Vivo Studies)
The health effects of RCF exposures have been evaluated in animal studies using intrapleural, intraperitoneal, intratracheal, and inhalation routes of exposure. All of these routes have demonstrated the carcinogenic potential of RCFs. Chronic inhalation studies provide information that is most relevant to the occupational route of exposure and human risk assessment. Mechanistic information about fiber toxicity may also be derived from other types of studies. Studies investigating the cellular effects of RCFs in vitro are reviewed in Section 5.2 and Appendix C.
When comparing the effects of a fiber dose in animal studies, it is possible to compare fibers on a gravimetric basis (effect per unit weight) or a fiber basis (effect per number of fibers).
The same gravimetric dose of different fiber types may contain vastly different numbers of fibers because of differences in their dimensions. RCF1 is a relatively thick fiber compared with many types of asbestos, such as chrysotile, a fiber commonly used as a positive control in pulmonary carcinogenesis experiments in animals (see Table 2-2 for descriptions of RCF1, RCF2, RCF3, and RCF4). A gravimetric dose of RCF1 usually contains far fewer fibers than the same gravimetric dose of chrysotile asbestos fibers, making a direct comparison of their effects difficult when the number of fibers per unit weight is not reported. Comparison on a perfiber basis rather than a weight basis provides information most applicable to occupational risk assessment.
Although the results of implantation and instillation studies may not be directly applicable to occupational exposure and human health effects, they provide important information about the potential toxicity of RCFs. Experiments that control fiber dimensions and other variables provide information about the physiological characteristics relevant to fiber toxicity. They provide a less expensive, quicker means to screen the potential toxicity of a fiber than inhalation studies.
Many of the implantation and instillation studies reviewed here report the administered fiber dose on a gravimetric basis rather than on a perfiber basis. Some studies assess the toxicity of both RCFs and asbestos independently, which allows for the comparison of these fibers on a gravimetric basis but not on a per-fiber basis.

# Intraperitoneal Implantation Studies
In intraperitoneal studies, fibers are implanted directly into the abdominal cavity, bypassing the respiratory system defense and clearance mechanisms that act on inhaled fibers. Although the implanted fibers act on some of the same target cell types as the fibers of an inhalation exposure (such as the mesothelium), the effects elicited in the abdominal mesothelium cannot be assumed to be identical to the response of the pleural mesothelium. Table 5-1 summarizes the results of three RCF intraperitoneal implantation studies . A brief description of these studies follows. Davis et al.  dosed Wistar rats with 25 mg ceramic aluminum silicate dust by intraperitoneal injection. Tumors were induced in 3 of 32 rats: 2 fibrosarcomas and 1 mesothelioma. Smith et al.  dosed Osborne Mendel (OM) rats and Syrian hamsters with 25 mg RCFs by intraperitoneal injection. Abdominal mesothelioma induction rates were 83%
(19/23) in OM rats and 13% (2/15) and 24%
(5/21) in two groups of male hamsters. Crocidolite asbestos at 25 mg induced abdominal mesotheliomas in 80% (20/25) of OM rats and 32% (8/25) of hamsters. The difference in tumor incidence reported by Davis et al.  and Smith et al.  may be explained in part by differences in fiber length. Eighty-three percent of RCF fibers used by Smith et al.  had a length >10 m; 86% had a diameter <2.0 m. Ninety percent of the ceramic aluminum silicate material used by Davis et al.  had a length <3 m and a diameter <0.3 m. Pott et al.  dosed female Wistar rats by intraperitoneal injection with 9 or 15 mg/week for 5 weeks with 2 ceramic (aluminum silicate) wool fibers, Fibrefrax (RCFs), and MAN (Manville RCFs); total doses of 45 and 75 mg were administered, respectively. Fifty percent of Fibrefrax fibers had a length <8.3 m and diameter <0.91 m. Exposure to Fibrefrax fibers induced abdominal tumors (sarcomas, mesotheliomas, or carcinomas) in 68% of the rats. Fifty percent of MAN fibers had a length <6.9 m and diameter <1.1 m. The number of fibers in different length categories was not reported. Exposure to MAN fibers induced abdominal tumors in 22% of the rats. Chrysotile (UICC/B) injected intraperitoneally at a single dose of 0.05, 0.25, or 1.00 mg induced abdominal tumors in 19%, 62%, or 86% of rats, respectively. Fifty percent of chrysotile fibers had a length <0.9 m and diameter <0.11 m. The number of fibers per dose was not reported for the ceramic fibers and asbestos. Saline induced tumors in 2% of rats.

# Intrapleural Implantation Studies
Intrapleural implantation studies permit the investigation of the effect of RCFs directly on the pleural mesothelium while controlling variables such as inhalation kinetics and translocation.  Table 5-2 summarizes the results of the intrapleural study of Wagner et al. . Intrapleural injection of 20 mg of ceramic fiber (unspecified type) or 20 mg for each of two samples of chrysotile produced mesotheliomas in 10% (3/31), 64% (23/36), and 66% (21/32) of Wistar rats, respectively. The mean ceramic fiber diameter was 0.5 to 1.0 m. The lengths of the chrysotile fibers were mostly <6 m. The chrysotile fiber diameter, RCF fiber length, and number of fibers per dose were not reported, making a direct comparison of the samples difficult.

# Intratracheal Instillation Studies
The technique of intratracheal instillation has the advantage of affecting the same target tissues (other than the upper respiratory tract) as an inhalation exposure. Other advantages, compared with inhalation exposure, include a simpler technique, lower cost, accurate dosing, and the ability to deliver materials (such as long fibers) that may not be respirable to rodents . The faster dose rate and bolus delivery of tracheal instillation may affect the response of the lung defense mechanisms, resulting in differences in clearance and biopersistence relative to an inhalation exposure. Intratracheal instillation may also produce a clumping of fibers with a resulting effect on fiber distribution and clearance . Intratracheal instillation results in a heavier, more centralized distribution pattern; inhalation exposure results in a more evenly and widely distributed pattern . Table 5-3 summarizes the results of two RCF intratracheal instillation studies . A brief description of these studies follows.
In the study by Smith et al. , Syrian golden hamsters and OM rats were dosed with 2 mg of RCFs suspended in saline (Fibrefrax) by intratracheal instillation once a week for 5 weeks (10 mg total). The animals were maintained for the rest of their lives. Approximately 50% of the RCFs were <20 m long with a mean fiber diameter of 1.8 m. No primary lung tumors developed in RCF-exposed animals. These animals did not have an increased incidence of pulmonary fibrosis or tumor production compared with controls; however, the rats had a statistically significant increase in bronchoalveolar metaplasia. The median lifespan was 479 days for hamsters and 736 days for rats. Hamsters (median lifespan 657 days) and rats (median lifespan 663 days) exposed to the same dosing schedule with 2 mg crocidolite asbestos had a statistically significant increase in bronchoalveolar lung tumors in 20 of 27 (74%) and 2 of 25 (8%) animals, respectively. The fiber numbers per dose were not reported.
Manville  reported a statistically significant increase in lung tumors in Fischer rats exposed intratracheally to 2 mg of RCF1, RCF2, RCF3, and RCF4 in saline . Animals were terminally sacrificed at 128 weeks with interim sacrifices at 13, 26, 52, 78, and 104 weeks. RCF1, RCF2, RCF3, and RCF4 exposure resulted in adenomas or adenocarcinomas in 6 of 109 (5.5%), 4 of 107 (3.7%), 4 of 109 (3.7%), and 7 of 108 (6.5%) rats, respectively. One mesothelioma was identified in a rat exposed to RCF2. Exposure to 0.66 mg chrysotile asbestos resulted in 8 primary lung tumors in 8 of 55 rats (14.5%). The fiber dimensions and numbers per dose were not reported.

# Chronic Inhalation Studies
In animal bioassays, administering RCFs by chronic inhalation most closely mimics the occupational route of exposure. Exposure to RCFs over a time period that approximates the lifespan of the animal provides the most accurate prediction of the potential pathogenicity and carcinogenicity of these fibers in animals. The sex ratio for all groups was approximately 2 male rats to 1 female rat.

# Tumor incidence
Manville  Fischer 344 rats 109, male 107, male 109, male 108, male 55, male 118, male 2 mg RCF1 (0.2 ml of a 10-mg/ml suspension) 2 mg RCF2 (0.2 ml of a 10-mg/ml suspension) 2 mg RCF3 (0.2 ml of a 10-mg/ml suspension) 2 mg RCF4 (0.2 ml of a 10-mg/ml suspension) 0.66 mg Canadian chrysotile (0.2 ml of a 3.3-g/ml suspension) 0.2 ml (vehicle not specified)  The effects seen in animals may be used to predict the effects of these fibers in humans, although interspecies differences exist in respiratory anatomy, physiology, and tissue sensitivity. Chronic inhalation studies provide the best means to predict the critical disease endpoints of cancer induction and nonmalignant respiratory disease that may occur in humans because of fiber exposure .
Five chronic RCF inhalation studies have been conducted on rats or hamsters . These studies are summarized in Tables 5-4 and 5-5 and are described below. Davis et al.  exposed Wistar rats by whole-body inhalation to 10 mg/m 3 (95 f/cm 3 ) ceramic (aluminum silicate glass) dust for 7 hr/day, 5 days/week for 12 months. Ninety percent of the exposure fibers were short (<3 m) and thin (<0.3 m). The particle ratio of nonfibrous particulate to fibers was 4:1. Eight of 48 exposed rats (17%) developed pulmonary neoplasms: 1 adenoma, 3 bronchial carcinomas, and 4 histiocytomas. Interstitial fibrosis was observed. No pulmonary tumors were observed in control animals. Smith et al.  exposed OM rats and Syrian golden hamsters by nose-only inhalation to 10.83.4 mg/m 3 (200 f/cm 3 ) ceramic fiber (Fibrefrax) for 6 hr/day, 5 days/week for 24 months. The ratio of nonfibrous particulate to fibers was 33:1. Exposure to RCFs did not induce pulmonary tumors in rats. One RCFexposed rat and one chamber control rat developed primary lung tumors. Rats exposed to RCFs had more severe pulmonary lesions than hamsters, and a greater percentage of rats had fibrosis than hamsters (22% versus 1%, respectively). Under similar conditions, exposure to 7 mg/cm 3 (3,000 f/cm 3 ) crocidolite asbestos produced pulmonary tumors in 3 of 57 rats, including 1 mesothelioma and 2 bronchoalveolar tumors. No pulmonary tumors were observed in crocidolite-exposed hamsters. Exposure to slag wool at 10 mg/m 3 (200 f/cm 3 ) and several fibrous glasses at similar gravimetric concentrations did not result in pulmonary neoplasms (not shown in Table 5-4). Mast et al.  exposed Fischer 344 rats by nose-only inhalation to 30 mg/m 3 (18753 WHO f/cm 3 RCF1, 22052 WHO f/cm 3 RCF2, 18266 WHO f/cm 3 RCF3, 15349 WHO f/cm 3 RCF4) of one of four types of RCFs for 6 hr/day, 5 days/week for 24 months and held until sacrifice at 30 months. Groups of 3 to 6 animals were sacrificed at 3, 6, 9, 12, 15, 18, and 24 months to examine lesions and determine fiber lung burdens. Other animals were removed from exposure at the same time points and held until sacrifice at 24 months. Positive control rats were exposed to 10 mg/m 3 (1.061.1410 4 WHO f/cm 3 ) chrysotile under similar exposure conditions. RCF fibers with a mean diameter of 1 m and mean length of 20 to 30 m were selected. A particle ratio of nonfibrous particulate to fiber of 1.02-1.88:1 was reported. Interstitial fibrosis was first observed at 6 months with RCF1, RCF2, and RCF3 and at 12 months with RCF4 exposure. Pleural fibrosis was first observed at 9 months with RCF1, RCF2, and RCF3 and at 12 months with RCF4 exposure. A progression in the severity of pleural fibrosis was seen in animals exposed to 30 mg/m 3 for 24 months and examined at 6 months post exposure. The incidence of total lung tumors was significantly increased from controls after exposure to RCF1, RCF2, and RCF3 but not RCF4. Neoplastic disease, including adenomas and carcinomas, was observed in all treatment groups: with RCF1, in 16 of 123 rats (13%); RCF2, 9 of 121 (7.4%); RCF3, 19 of 121(15.7%); RCF4, 4 of 118 (3.4%); and chrysotile, 13 of 69 (18.5%). Mesotheliomas were induced in some rats in all treatment groups: 2 with RCF1; 3 with RCF2; 2 with RCF3; 1 with     RCF4; and 1 in the chrysotile exposure group. All mesotheliomas were detected at or after 24 months of exposure. Most RCF fibers recovered in the lung were 5 to 10 m long regardless of exposure time and recovery time. An 80% reduction in fiber lung burden was seen in rats allowed to recover for 21 months following 3 months of RCF exposure. Mast et al.  exposed Fischer 344 rats by nose-only inhalation to 0 (air), 3, 9, or 16 mg/m 3 (0, 2612, 7535, or 12035 WHO f/cm 3 ) RCF1 for 6 hr/day, 5 days/week for 24 months and held them until sacrifice at 30 months. Fibers were selected by size as in Mast et al. .
A particle ratio of nonfibrous particulate to fibers of 0.9-1.5:1 was reported. Groups of 3 to 6 animals were sacrificed at 3, 6, 9, 12, 18, and 24 months to examine lesions and determine fiber lung burdens. Other animals were removed from exposure at the same time points and held until sacrifice at 24 months. Interstitial fibrosis was observed after 12 months of exposure in the 9-and 16-mg/m 3 exposure groups. Pulmonary fibrosis was first observed after 12 months with 16 mg/m 3 exposure and after 18 months with 9 mg/m 3 exposure. The mean Wagner grades of pulmonary cellular change and fibrosis in rats exposed to 0, 3, 9, 16, and 30 mg/m 3 of RCFs for 24 months were 1.0, 3.2, 4.0, 4.2, and 4.0, respectively. Rats exposed at the same range of doses for 24 months and allowed to recover for 6 months had mean Wagner grades of 1.0, 2.9, 3.8, 4.0, and 4.3. The severity of interstitial and pleural fibrosis was similar between those animals sacrificed at 24 months and those allowed 6 months of recovery following the 24 months of exposure. The incidence of pulmonary neoplasms was not statistically different from the controls in all exposure groups. One pleural mesothelioma was observed in the 9-mg/m 3 exposure group. A dose-related increase occurred in fiber lung burden. Fiber lengths of 5 to 10 m were most prevalent in the lung fibers recovered after 3 months of exposure followed by 21 months of recovery, after 12 months of exposure, and after 24 months of exposure to all doses of RCFs. Animals exposed for 3 or 6 months and then allowed to recover until sacrifice at 24 months had lung burdens reduced by 96% to 97% compared with animals not allowed recovery time.
McConnell et al.  exposed Syrian golden hamsters by nose-only inhalation to 30 mg/m 3 RCF1 (25658 WHO f/cm 3 ) for 6 hr/day, 5 days/week for 18 months and held them until sacrifice at 20 months. Positive control animals were exposed to 10 mg/m 3 (8.49.010 4 WHO f/cm 3 ) chrysotile asbestos. Groups of 3 to 6 animals were sacrificed at 3, 6, 9, 12, 15, and 18 months to examine lesions and determine fiber lung burdens. Other animals were removed from exposure at the same time points and held until sacrifice at 20 months. Interstitial and pleural fibrosis were first observed after 6 months of exposure in RCF-exposed hamsters. No pulmonary neoplasms developed. Forty-two of 102 (41.2%) RCF-exposed animals developed pleural mesotheliomas. Most mesotheliomas developed after 18 months of exposure. Animals exposed to chrysotile developed a more severe interstitial fibrosis and pleural fibrosis than those exposed to RCFs. No neoplasms were observed in the lungs or pleura of the chrysotile-exposed or air control animals. The greatest percentage of retained fibers had lengths of 5 to 10 m and diameters <5 m in the lungs after 6 months of exposure followed by 12 months of recovery.
McConnell et al.  conducted a multidose chronic study of the effects of amosite inhalation in hamsters. The data can be compared with the effects of RCF1. Syrian golden hamsters were exposed to 0.8 (3623 WHO f/cm 3 ), 3.7 (16561 WHO f/cm 3 ), or 7 mg/m 3 (26390 WHO f/cm 3 ) amosite asbestos. Pleural mesothelioma incidences of 3.6%, 25.9%, and 19.5%, respectively, were reported. The aerosol mean diameter of the amosite asbestos was 0.60 m 0.25; its aerosol mean length was 13.4 m 16.7. The dimensions of this asbestos fiber were more similar to those of the RCFs used in the chronic inhalation studies of McConnell et al.  than the chrysotile asbestos used as the positive control in that same study.
NIOSH  analyzed the hamster data from the RCF  and amosite studies . A doseresponse model was developed for amosite and was used to predict the amosite response at the one and only dose at which RCFs were tested in hamsters. The modeled amosite response was compared with the observed RCF response. These results are presented in Figures 5-1 and 5-2. Log-probit, log-logistic, multistage, and unrestricted Weibull models were analyzed.
The transformation for the log-probit and log-logistic models was log (fibers/cm 3 +1).
The dose metric of the multistage and Weibull models was fibers/cm 3 , as they did not require a log-transformation. Results of the log-probit model analysis of these data indicated RCF/ amosite relative potency estimates of 1.85 and 1.19, using WHO fibers and fibers >20 m as the dose metric, respectively. The model fits were poor when the amosite high-dose group and 20 m-fiber dose were included. Sensitivity analyses in which the high-dose amosite group was dropped suggest that the relative potency of RCFs to amosite could be as low as 0.66 based on the log-probit model. Results using the log-logistic, multistage, and Weibull models were similar to those using the log-probit model, with an overall range of RCF/amosite relative potency estimates from these models using all four amosite dose groups of 1.03 to 1.89. Although no clear toxicologic basis exists for disregarding the high-dose amosite data, sensitivity analyses based on excluding these data suggest that the potency of RCFs relative to amosite could be as low as 0.47, based on the multistage model. These models indicate that the plausible carcinogenic potency estimates for RCFs relative to amosite, based on hamster mesotheliomas, range from about half to nearly twice the carcinogenicity of amosite.

# Discussion of RCF Studies in Animals
The intrapleural, intraperitoneal, and intratracheal RCF studies have demonstrated the carcinogenicity of RCFs. Because of the nonphysiologic delivery of fibers by these methods, it is difficult to compare their results with those of an inhalation exposure. Although tracheal instillation may result in different distribution patterns than an inhalation exposure, this route of exposure is useful as a screening test for relative toxicity and to compare the toxicity of new materials with the toxicity of materials for which data already exist . Tracheal instillation also is useful when testing fibers respirable by humans but not rodents. Chronic inhalation studies provide the data most relevant to occupational exposure to RCFs.
The RCF chronic animal inhalation studies described above allow for the comparison of health effects of exposure to different doses of RCF1, different types of RCFs, and the interspecies susceptibility of the rat and hamster to RCF exposure.
Results of the multidose chronic inhalation testing of RCF1 in rats indicate the pathogenic potential of RCFs at high doses . The incidence of total lung tumors was significantly increased from controls after exposure to 30 mg/m 3 RCF1, RCF2, and RCF3 but not RCF4. A dose-response relationship was demonstrated for nonneoplastic pulmonary changes in rats exposed to 3, 9, and 16 mg/m 3 RCFs. The severity of interstitial and pleural fibrosis was similar between those animals sacrificed at 24 months and those allowed 6 months  .) of recovery following the 24-month exposure. Spontaneous primary pulmonary mesotheliomas are rare in rats . Therefore, the presence of any mesothelioma in treated animals is biologically significant and warrants caution.
Comparing the chronic effects of RCF1 with its positive control, chrysotile asbestos, in the hamster is difficult because of the differences in dose, dimensions, and durability of the two fibers tested . Differences in the physical characteristics and biopersistence of RCF1 and amosite asbestos must be considered before extrapolating these animal data to human risk.
Hamsters showed a greater susceptibility to mesothelioma induction after RCF1 exposure than did rats under similar exposure conditions . Chronic inhalation studies of amosite asbestos in hamsters showed no pulmonary neoplasms, but high incidences of mesothelioma occurred at doses of 125 and 250 f/cm 3 . Many of the mesotheliomas in the more recent hamster studies were identified only on microscopic examination [Mast et al. 1995a;McConnell et al. 1995McConnell et al. , 1999. Previous studies reporting mesotheliomas only by macroscopic identification may have underestimated the mesothelioma incidence. Recent, short-term inhalation studies indicate that hamster mesothelial cells may have a more pronounced inflammatory and proliferative response to RCF1 exposure than those of rats [Everitt 1997;Gelzleichter et al. 1996aGelzleichter et al. ,b, 1999. The reasons for this species difference in response to RCFs have not been explained. The results of these animal studies indicate the need for the inclusion of the hamster as a sensitive test species in those studies in which pleural mesothelioma is an endpoint of concern.
Results from Mast et al.  indicate that under the conditions studied, exposure to RCF4 may have a less pronounced effect on pulmonary pathology than exposure to RCF1, RCF2, and RCF3. Rats exposed to RCF4 did not have a significant increase in total lung tumors compared with controls; those exposed to RCF1, RCF2, and RCF3 did. Exposure to RCF4 produced a less severe fibrosis than was seen in the other RCF exposure groups. Differences in the dimensions or physical properties of RCF4 may explain its different respiratory effects from RCF1, RCF2, and RCF3. RCF4 was produced by heating RCF1 in a furnace at 2,400 o F for 24 hr. This Aafter-service@ fiber contained approximately 27% free crystalline silica. Silicotic nodules were observed in the RCF4-exposed animals. RCF4 fibers were shorter (~34% between 5 and 10 m ) and thicker (~35% <0.5 m) than those of RCF1, RCF2, and RCF3.
The particle content of the RCF test material may have been responsible for some of the respiratory pathology observed in these studies.
However, an analysis of the ratio of nonfibrous to fibrous particulates in the reviewed studies does not indicate a correlation between the particulate content and observed effects. Smith et al.  performed testing with the highest particulate to fiber ratio at 33:1 and did not report a high tumor incidence. Comparing studies based on the ratio of nonfibrous particulates to fibers is complicated by differences among the studies in fiber preparation, doses tested, fiber dimensions, and methods of fiber analysis. The techniques used to detect and measure nonfibrous particulates have improved over time so that the comparison of recent and older studies may reflect these inconsistencies.
These chronic RCF inhalation studies indicate the ability of RCFs to induce cancer in two laboratory species-mesotheliomas in hamsters and pulmonary tumors in rats. The late onset of tumors indicates the importance of chronic studies on the effects of RCF exposure. Shortterm intraperitoneal, intrapleural, intratracheal, and inhalation studies provide important information about the action of fibers, the fiber characteristics associated with toxicity, and potential toxicity. Currently it is only through lifespan toxicologic testing of animals that the respiratory and other chronic health effects of RCFs can be accurately assessed.

# Lung Overload Argument Regarding Inhalation Studies in Animals
Mast et al.  published a review interpreting the results of chronic inhalation studies of RCF1 in rats and hamsters . In the review, the authors suggest the possibility that the maximum tolerated dose (MTD) may have been exceeded and that lung overload may have compromised the pulmonary clearance mechanisms of test animals. Building on the concept of lung overload (first advanced by Bolton et al. ), Mast et al.  considered particulate coexposure (i.e., nonfibrous particulate or shot) to be a confounding factor that may have had a major effect on the observed chronic adverse effects. The authors propose that the MTD was exceeded at the highest exposure concentration of 30 mg/m 3 for RCF1 in the rat bioassay.
The concept of pulmonary overload in the Fischer 344 rats is based on the recognition that excessive particulate exposures (>1,500 g/rat, according to Bolton et al. ) eventually reduce the clearance effectiveness of the lungs, causing the normal linear clearance kinetics to follow a nonlinear pattern. On a cellular level, the overload conditions may result in alveolar macrophages becoming engorged with particulate, pulmonary and alveolar inflammation, increased translocation of particles to the interstitium and lymph, granuloma formation, pulmonary fibrosis, and lung tumors, depending on the time and severity of the overload . Ambiguity about the definition of MTD for chronic inhalation studies with animals was also a concern expressed by the authors. One reference  recognizes the MTD as that which causes "a significant functional impairment of lung clearance." At a National Toxicology Program (NTP) workshop on establishing exposure concentrations for inhalation studies in animals, it was concluded that the highest exposure concentration should produce only minimal changes in lung defense mechanisms as measured by clearance . At a similar workshop convened by the EPA, it was proposed that the MTD for fiber inhalation studies is equivalent to the lung dose produced at the maximum achievable concentration (MAC) . The MAC is calculated as the highest fiber concentration based on a 90-day study that results in significant changes in alveolar macrophage clearance rates, lung burden normalized to exposure concentration, cell proliferation, inflammation, lung weight, and other measures.
The methodology described for the RCF chronic inhalation studies involved procedures (i.e., wet cyclone separation technology) for removing the nonfibrous particulate fraction from the commercial fiber (RCF1) used for the inhalation exposures . This process resulted in an aerosol with a 9.1:1 particle-to-fiber ratio , compared with a study by Smith et al. , which reported 33 nonfibrous particles per fiber in airborne exposures. Results from Esmen et al.  indicate that despite a poor correlation between mass of total airborne dust and fiber concentration in RCFs measured in manufacturing, fibers generally constitute only a small portion of the total dust. This finding is consistent with other reported measures of occupational exposures to airborne RCFs . However, Maxim et al.  reported an average particle-to-fiber ratio of 0.53:1 (n=10, range not reported), or roughly 1 particle to 2 fibers in RCF manufacturing facilities. Muhle and Bellmann  conducted a 5-day inhalation study with Fischer 344 rats to measure the biopersistence of RCF1 (with the 9:1 particulate-to-fiber ratio) and RCF1a (RCF1 that is further processed to reduce particulate mass). The study showed a 1.5-fold longer time-weighted half-life for RCF1 (t 1/2 =78 days) compared with RCF1a (t 1/2 =54 days). That study also involved a 3-week inhalation experiment with Fischer 344 rats, in which the clearance of RCF1 (t 1/2 =103 days) was almost twice as long as that of RCF1a (t 1/2 =54 days).
In a follow-up study by Brown et al. , female Wistar rats were exposed to RCF1 and RCF1a by inhalation for 3 weeks and followed for 12 months to evaluate alveolar macrophage clearance and inflammation. The exposure concentrations were 130 fibers/ml >20 m for RCF1 and 125 fibers/ml >20 m for RCF1a. The nonfibrous content of RCF1 was approximately 25%, whereas the nonfibrous content of RCF1a was 2%. The mean diameter of the nonfibrous particles was 2 to 3 m. The aerosol exposure to RCF1 contained twice as many short fibers (<20 m) as RCF1a and twice the amount of dust (fibers and nonfibrous dust/ mg - m 3 ) as RCF1a (51 versus 25.8 mg/m 3 ). At the end of the inhalation period, animals exposed to RCF1a had a higher pulmonary concentration of long fibers but lower concentrations of short fibers and nonfibrous particles. The difference in particle content was enhanced in the lungs-15 times more particles were found in the lungs of the RCF1-exposed animals than in those exposed to RCF1a. In the aerosol exposure, only an eightfold difference was found in the number of particles between RCF1 and RCF1a.  Tran et al.  examined how overloading the alveolar macrophage defense system affects the clearance of fibers versus that of nonfibrous particles. Modeling was performed based on data for rats exposed by inhalation to titanium dioxide (TiO 2 ) at 1, 10, and 50 mg/m 3 or to glass wool (MMVF10) at 3, 16, and 30 mg/m 3 . Lung burdens and clearance kinetics during exposure (0 to 100 weeks) were compared with those at 3, 10, and 38 days post-exposure. The models showed that overloading of the lung by fibers or nonfibrous particles are similar when fibers are short (<15 m). This observation is plausible, as nonfibrous particles and short fibers smaller than the diameter of the alveolar macrophage are most readily engulfed and cleared via the macrophages. When this defense is overwhelmed (lung burden 10 mg), these particles are cleared less effectively. For fibers longer than 15 m, phagocytosis by alveolar macrophage is reduced. As fiber length increases, fibers tend to be cleared by dissolution and disintegration of long fibers into shorter fibers or fragments. Therefore, clearance of long fibers is not affected by the overloading of macrophage-mediated defenses with shorter fibers or nonfibrous particles.
The exposure concentrations for the RCF chronic inhalation bioassays were measured and reported as mass in mg/m 3 . Monitoring of exposures as performed by gravimetric analysis does not distinguish fibers from nonfibrous particulate, although fiber concentration and dimensions were also checked by phase contrast and electron microscopy . Consequently, the particulate fraction was included in the dose measurements. This fact does complicate efforts to compare the relative toxicity of fibers, nonfibrous particulate, and total combined particulate, especially regarding the lung overload hypothesis. During pro-duction of RCFs and RCF products, however, the nonfibrous particulate fraction is associated with the fiber, as shown in Table 2-1 (i.e., 20% to 50% of RCFs by weight is nonfibrous particulate). This suggests that occupational exposures to airborne RCFs necessarily involve coexposures to a fraction of nonfibrous particulate, a suggestion that has been supported by exposure assessment studies .

# Cellular and Molecular Effects of RCFs (In Vitro Studies)
The cellular and molecular effects of RCF exposures have been studied with two different objectives. One purpose of these in vitro studies is to provide a quicker, less expensive, and more controlled alternative to animal toxicity testing. These experiments are best interpreted by comparing their results with those of in vivo experiments. The second objective of in vitro studies is to provide data that may help to explain the pathogenesis and mechanisms of action of RCFs at the cellular and molecular levels. These cytotoxicity and genotoxicity studies are best interpreted by comparing the effects of RCFs with those of other SVFs and asbestos fibers. In vitro studies serve as screening tools and provide insights into the molecular mechanisms of fibers. They are an important complement to animal studies. Currently it is not possible to use these data to derive the NIOSH REL for RCFs. For this reason, a discussion of in vitro studies is included here, but the more comprehensive summaries of studies are included in Appendix C.
The toxicity of fibers has been attributed to their dose, dimensions, and durability. Any test system that is designed to assess the potential toxicity of fibers must address these factors. Durability is difficult to assess using in vitro studies because of their acute time course. However, in vitro studies provide an opportunity to study the effects of varying doses and dimensions of fibers in a quicker, more efficient method than animal testing. They do not currently provide data that can be extrapolated to occupational risk assessment.
The association between fiber dimension and toxicity has been documented and reviewed . RCFs may have different toxicities, depending on the fiber length relative to macrophage size. Longer fibers are more toxic. Fiber length has been correlated with the cytotoxicity of glass fibers . Manville code 100 (JM-100) fiber samples with average lengths of 3, 4, 7, 17, and 33 m were assessed for their effects on LDH activity and rat alveolar macrophage function. The greatest cytotoxicity was reported in the 17-and 33-m samples, indicating that length is an important factor in the toxicity of this fiber. Multiple macrophages were observed attached along the length of long fibers. Relatively short fibers (<20 m) were usually phagocytized by one rat alveolar macrophage . Longer fibers were phagocytized by two or more macrophages. Incomplete or frustrated phagocytosis may play a role in the increased toxicity of longer fibers. Long fibers (17 m average length) were a more potent inducer of tumor necrosis factor (TNF) production and transcription factor activation than shorter fibers (7 m average length) . These studies demonstrate the important role of length in fiber toxicity and suggest that the capacity for macrophage phagocytosis may be a critical factor in determining fiber toxicity.
Several of the in vitro RCF studies (summarized in Appendix C) reported a direct association between a longer fiber length and greater cytotoxicity. Hart et al.  reported the shortest fibers to be the least cytotoxic. Brown et al.  reported an association between length, but not diameter, and cytotoxic activity. Wright et al.  reported that cytotoxicity was correlated with fibers >8 m long. Yegles et al.  reported that the longest and thickest fibers were the most cytotoxic. The four most cytotoxic fibers had GM lengths 13 m and GM diameters >0.5 m. The production of abnormal anaphases and telophases was associated with Stanton fibers with a length >8 m and diameter <0.25 m. Hart et al.  reported that cytotoxicity increased with increasing average fiber lengths from 1.4 to 22 m, but did not increase with average lengths from 22 to 31 m.
Additional studies assessing the cytotoxicity of specific RCF fiber lengths are needed. Such studies will help to describe the association between fiber length and toxicity for RCFs and may allow determination of a threshold length above which toxicity increases significantly.
In addition to providing data on the correlation between fiber length and toxicity, in vitro studies have provided data on the relative toxicity of RCFs compared with other fibers, although some uncertainties remain in the interpretation of these studies because of differences in fiber doses, dimensions, and durabilities. RCFs have direct and indirect effects on cells and alter gene function in similar ways. They are capable of inducing enzyme release and cell hemolysis. They may decrease cell viability and inhibit proliferation. RCFs affect the production of TNF and reactive oxygen species (ROS) and affect cell viability and proliferation. They induce necrosis in rat pleural mesothelial cells. They may also induce free radicals, micronuclei, polynuclei, chromosomal breakage, and hyperdiploid cells in vitro.
In vitro studies provide an excellent opportunity for investigating the pathogenesis of RCFs. However, comparisons are difficult to make between in vitro studies based on differences in fiber doses, dimensions, preparations, and compositions. Important information such as fiber length distribution is not always determined. Even when comparable fibers are studied, the cell line or conditions under which they are tested may vary. Much of the research to date has been done in rodent cell lines and in cells that are not related to the primary target organ. In vitro studies using human pulmonary cell lines should provide pathogenesis data most relevant to human health risk assessment.
Short-term in vitro studies cannot take into account the influence of fiber dissolution and fiber compositional changes that may occur over time. In an in vivo exposure, fibers are continually modified physically, chemically, and structurally by components of the lung environment. This complex set of conditions is difficult to recreate in vitro. Just as it is unlikely that only one factor is an accurate predictor of fiber toxicity, it is unlikely that any one in vitro test is able to predict fiber toxicity.

# Health Effects in Humans

# Morbidity and Mortality Studies
Two major research efforts evaluated the morbidity of RCF-exposed workers-one conducted in U.S. plants and one in European plants.  . A followup cross-sectional study conducted in 1996 evaluated the same medical endpoints in workers from six of these seven European manufacturing plants (one plant had ceased operation) [Cowie et al. 1999[Cowie et al. , 2001. Current and former workers were included as study subjects in the followup study.
The studies of U.S. plants began in 1987 and involved evaluations of current workers at five RCF manufacturing plants and former workers at two RCF manufacturing plants [ Lemasters et al. 1994Lemasters et al. , 1998Lockey et al. 1993Lockey et al. , 1996Lockey et al. , 1998Lockey et al. , 2002.
In the United States, the earliest commercial production of RCFs and RCF products began in 1953; in Europe, RCF production began in 1968. The demographics of the U.S. and European populations were similar at the time they were studied, although the average age of U.S. workers was slightly higher than that of the workforce in the 1986 European studies because of the earlier development of this industry in the United States. The mean age for the European RCF workers was 37.7 in the 1986 study  and 42.0 for males and 39.4 for female workers in the 1996 study . In the U.S. RCF manufacturing industry, the average age is 40 for current workers and 45 for former workers . The mean duration of employment in the European cohort was 10.2 years (range 7.2 to 13.8 years) in 1986  and 13.0 years in 1996 . The U.S. study reports the mean duration of employment for 23 workers with pleural plaques as 13.6 years (9.8); the median is 11.2 years (range 1.4 to 32.7) .
The following text and  From a possible 708 current workers, 628 eligible participants were identified and 596 had chest X-ray examinations; 51 female workers and 13 unexplained others were excluded from analysis.
From a possible 708 current workers, 628 eligible participants were identified and 596 had chest X-ray examinations; 2 unreadable films and those of 51 female workers were excluded from the analysis.   Study included current workers at six ceramic fiber manufacturing plants in three European countries as well as leavers from the first three European studies [Burge et al. 1995;Rossiter et al. 1994;Trethowan et al. 1995 From a possible 868 eligible current and former workers at 2 plant sites, 148 were eliminated for lack of exposure characterization data and loss to followup. Of the remaining 720 workers, 68 did not agree to chest X-ray examinations.   
From a possible 963 eligible current workers at five plant sites, 209 female workers were excluded as well as 393 male workers with fewer than 5 PFT sessions.
mortality studies is also presented in Section 5.3.5 . Two HHEs of workplaces involving workers exposed to RCFs are also described in Section 5.3.6 .

# Radiographic Analyses
In both the European and U.S. studies cited in Table 5-6, the study populations included workers at multiple plants involved in the manufacture of RCFs or RCF products. As part of the investigation of potential effects of exposure to airborne RCFs, chest radiography was performed. In all studies, chest radiographs were read independently by three readers using the International Labour Office (ILO) 1980 International Classification of the Radiographs of Pneumoconioses . Identifiers on films were masked to ensure a blind review by readers, and quality control measures and tests of agreement were used to check consistency among the readers. For each type of abnormality analyzed, the median of the three readings for each film was used.

# Pleural abnormalities
In the 1986 study of European RCF workers, results of the chest radiography indicated a prevalence of 2.8% (15/543) for pleural abnormalities among male workers .
Of the 15 cases with pleural abnormalities, 4 had bilateral diffuse thickening (1 with calcification), 1 showed bilateral pleural calcification only, 7 presented with unilateral diffuse thickening, and 3 showed costophrenic angle blunting only. The possibility for confounding effects was recognized because of other exposures: 52% of workers reported previous employment in dusty jobs, including 4.5% with prior asbestos exposures and 7% with prior MMMF exposures. When female workers were included in the same population, Trethowan et al.  reported a prevalence of 2.7% (16/592) for pleural abnormalities. Two cases were known to have previous exposure to asbestos, and the possibility for exposure to other respiratory hazards was acknowledged for other persons with pleural abnormalities. Cowie et al. [1999Cowie et al. [ , 2001 reported pleural abnormalities in 10% (78/774) and     [Rice et al. 1994[Rice et al. , 1996.

# Exposure:
Controls and cases reinterviewed with additional questions regarding asbestos exposure (application, manipulation, and distance from exposure). Asbestos exposure categorized (rating index = high, medium, low) from interview data.

# Radiographic analyses
In the cohort study, 20 cases of pleural plaque were identified in the cohort: 18 production workers and 2 nonproduction workers.
In            Cowie et al. 1999Cowie et al. , 2001 (European study) Cowie et al. 1999Cowie et al. , 2001 Respiratory health assessment Groat et al. 1999 Exposure assessment

# Evaluation methods

# Results

# Comments
Cross-sectional study:  Rossiter et al.  reported an association with age . However, no attempt was made to assess whether an association existed between pleural abnormalities and RCF exposure. Trethowan et al.  also noted that pleural abnormalities were related to age but not independently to ceramic fiber exposures. Cowie et al.  found that pleural abnormalities were associated with time since first RCF exposure (RCF latency) after adjusting for duration of asbestos exposure and time since first asbestos exposure (odds ratio =2.9 . A latency validity review was also conducted, involving analysis of 205 historical chest radiographs available for workers with pleural changes. The purpose of the review was to confirm that for persons with pleural plaques, a biologically plausible latency period (5 years) existed between initial RCF exposure and appearance of a pleural plaque. Of 18 pleural plaque cases for which historical chest radiographs were available, only 1 had a latency period of <5 years from initial RCF production to recognition of a pleural plaque.
A subsequent analysis by Lockey et al.  included chest radiographs for 625 current workers obtained every 3 years at 5 RCF manufacturing sites and 383 former workers at 2 of the 5 sites. Pleural changes were seen in 27 workers (2.7%), of which 19 were bilateral plaques (70%) and 3 were unilateral plaques (11%). Cumulative RCF exposure (>135 fibermonths/cm 3 ) was significantly associated with pleural changes (OR = 6.0, 95% CI = 1.4, 31.0). The researchers noted an increasing but nonsignificant trend involving interstitial changes and RCF exposure duration in a production job and cumulative RCF exposure.

# Parenchymal Opacities
In the 1987 European study, Rossiter et al.  found that 7% (38/543) of the current male workers had small parenchymal opacities with median profusion of 1/0 or more. No large parenchymal opacities were observed. Both predominantly rounded (n=23, or 4.2%) and predominantly irregular (n=15, or 2.8%) small parenchymal opacities were identified. In a subsequent analysis of small opacities for both male and female workers, Trethowan et al.  noted that the prevalence of small opacities increased with age, smoking, and previous exposure to asbestos but not with cumulative RCF exposure. No description of the analysis was provided. Cowie et al.  reported that 10 of 51 (19.6%) men with RCF exposure before 1971 had small opacities of category 1/0 or greater. Eight of these 10 had been exposed to asbestos, and 9 were either current or ex-smokers. In the U.S. study, no analyses were performed to assess the relationship between small opacities and RCF exposure because of the small number of cases (n=4) identified by Lemasters et al. [1994.

# Respiratory Conditions and Symptom Analyses
Using respiratory health questionnaires, the U.S. and European studies sought to identify respiratory conditions and symptoms that could be associated with exposure to RCFs. Lockey et al.  administered to 717 subjects a standardized respiratory symptoms questionnaire that included questions about the following symptoms and conditions: chronic cough, chronic phlegm, dyspnea grades 1 and 2 (described in the Definitions section of this document), wheezing, asthma, pleurisy, and pleuritic chest pain. Logistic regression analyses were adjusted for age, sex, smoking (pack years), duration of asbestos exposure, duration of production employment, duration of other hazardous occupational respiratory exposure, and time since last RCF employment. With the exception of asthma, for which self-selection out of production jobs may have occurred, adjusted ORs for respiratory symptoms were significantly elevated in production workers compared with nonproduction workers. Results of a subsequent analysis with 742 RCF workers by Lemasters et al.  indicated that the prevalence of respiratory symptoms and conditions (except for asthma) was approximately twofold to fivefold higher in production than in nonproduction workers. The most frequently reported symptom for male production workers was dyspnea grade 1 (15.7%, compared with 2.5% for nonproduction), followed by wheezing (10.3%, compared with 3.8% for nonproduction). Prevalence of one or more respiratory symptoms and conditions among female production workers was 40.7%, compared with 20.3% for nonproduction workers. Trethowan et al.  examined the relationship of dry cough, chronic bronchitis, dyspnea (two grades), wheeze, stuffy nose, eye irritation, and skin irritation to current and cumulative RCF exposure estimates among 628 workers. Current exposures were based on air sampling measurements taken in association with the respiratory health survey. The researchers noted eye and skin irritation were frequent in all plants and increased significantly, as did dyspnea and wheeze, with increasing current exposure concentrations (i.e., 0.2 to 0.6 and 0.6 f/cm 3 ) after controlling for age, sex, and smoking habits. The most frequent symptom, nasal stuffiness (in 55% of the group), showed no clear association with increasing current exposure. Chronic bronchitis, with a prevalence of 12% among all workers, also appeared unaffected by increasing current exposure concentration. Dry cough, eye irritation, and skin irritation all seemed to be associated with increasing exposure, especially at the highest exposure concentration (0.6 f/cm 3 ). Analyses of cumulative exposure to respirable fibers showed statistically significant associations with dyspnea but no apparent association with chronic bronchitis and wheeze. In a separate analysis of the same cohort,  investigated the relative importance of respirable RCF exposure versus inspirable dust exposure in predicting respiratory symptoms and conditions. The study found work-ers= current exposures to both inspirable dust and respirable fibers were related (P7 RCF production years, smoking status (pack years, current versus former smoker), weight, and plant location (categorical). The analysis found decreases in FVC and FEV 1 for workers employed >7 years in production compared with nonproduction workers. In longitudinal analyses of followup production years (i.e., from initial PFT to final PFT) and followup cumulative exposure (i.e., from initial PFT to final PFT), neither of these variables had an effect on FVC or FEV 1 . These results led the authors to conclude that more recent exposure concentrations during 1980-1994 had no adverse effect on the longitudinal trend of pulmonary function ]. Decrements in FVC and FEV 1 noted in initial cross-sectional analyses of PFT data were believed to be related to earlier higher exposure concentrations.

# Pulmonary Function Testing

# Mortality Studies
Table 5-8 presents findings from a cohort mortality study of two U.S. RCF production plants reported by Lockey et al. . The study is based on a cohort of 684 male workers at two RCF production plants who were employed for at least 1 year between January 1, 1950, and June 1, 1988. Five workers were lost to followup and 46 were deceased. Because this is a relatively new industry (40 years at the time of the study) that has experienced recent growth of the workforce at the plants studied, personyears at risk were limited at higher latencies (for example, only 126.37 person-years with >30 years since first RCF job). Using standardized mortality ratios (SMRs), the authors found The mortality was also lower than would be expected if RCFs had the potency of chrysotile, but the difference is not statistically significant.
For mesothelioma, the authors concluded the anticipated numbers of deaths under hypotheses of asbestos-like potency are too small to be rejected by the zero cases seen in the RCF cohorts . NIOSH researchers noted that this analysis by Walker et al. was not based on the most current update of the RCF cohort. In addition, the asbestos risk assessment models used by Walker et al.  were fitted to studies with longer followup periods than the cohort of RCF workers. Because these models do not specify length of followup, it is not possible to adjust for these differences. Consequently, it is likely that the RCF cohort has not been followed for a sufficient length of time to demonstrate the risks that were observed in the asbestos cohorts. NIOSH believes the mortality study by Lemasters et al.  and the risk analysis by Walker et al.  have insufficient power for detecting lung cancer risk based on what would be predicted for asbestos.

# NIOSH HHEs
As part of its mission as a public health agency, NIOSH performs HHEs at the request of workers, employers, or labor organizations to investigate occupational hazards associated with a workplace or work-related activity. One such HHE involved evaluating worker exposures to ceramic fibers at a company manufacturing steel forgings . At the facility, furnaces for heat-treating steel ingots were lined with RCF felt and batting, and this lining required regular maintenance and replacement. Among the workers interviewed were six bricklayers involved in furnace lining maintenance. Four of the bricklayers reported having experienced irritation of exposed skin areas and of the throat during the handling and installation of the RCF-containing insulation. On the basis of the reported symptoms and their consistency with known effects of RCFs, the symptoms of irritation were attributed to RCF exposure. No attempt was made to measure airborne fiber concentrations. Another NIOSH HHE  resulted from an OSHA inspection that identified 18 cases of occupational lung disease recorded in 1 year at a plant manufacturing fire bricks, ceramic fiber products, and other thermal insulation components from kaolin. About 600 workers were potentially exposed to respiratory hazards that included not only RCFs but also kaolin dust, crystalline silica dust, and (for maintenance workers) asbestos. A total of 38 workers had been referred to a pulmonary physician for evaluation based on 2 rounds of chest X-ray screening of the workforce in 1980 and 1986. Diagnoses were related to pleural thickening (n=10), pleural plaques (n=3), diffuse pulmonary fibrosis (n=21), mesothelioma (n=1), and other miscellaneous conditions. At least 20 of these cases were classified as work-related by the pulmonologist who evaluated the cases. The nonoccupational classification of some of the remaining 18 cases was questioned by a NIOSH physician who performed a retrospective record review. The 38 cases were reclassified on the basis of job histories into those who were likely to have been exposed to RCFs (n=19, including 4 with pleural abnormalities and 8 with diffuse fibrosis) and those unlikely to have been exposed to RCFs (n=19, including 9 with pleural abnormalities, 13 with fibrosis, and 1 with mesothelioma). However, no attempt was made to analyze further for an association of the cases with exposure to RCFs. The report implied that occupational exposure to kaolin dust and to asbestos caused many or all of the job-related conditions.

# Discussion
The radiographic analyses of the U.S. and 1996 European worker groups suggest an association between pleural abnormalities, including pleural plaques, and RCF exposure . From Rossiter et al.  it is less apparent whether such an association was investigated. Trethowan et al.  report that pleural abnormalities were not independently related to RCF exposure. Differences between the findings of the U.S. studies and those of the initial European studies may be related to the long latency before pleural abnormalities are detectable, in particular, pleural plaques following RCF exposure. Workers exposed to asbestos developed asbestos-associated pleural plaques after a latency period of more than 15 years after initial exposure  and in some cases, after 30 to 57 years  began to supplement these views with left and right 45 o oblique view films as a standard practice for radiographic surveillance. This methodology, known as a film triad, was evaluated against the posteroanterioronly view to determine reliability, sensitivity, and specificity of each method . The evaluation, involving 652 subjects in the RCF study, showed the film triad had considerably higher interreader reliability (=0.59) than the posteroanterior-only method (=0.44). The authors concluded that the film triad method provides an optimum approach.
The U.S. and 1986 European studies yielded little evidence of an association between radiographic parenchymal opacities and RCF exposure. In the U.S. study, small opacities were rare . Small opacities of profusion category 1/0 or greater were more frequent in the 1986 European study , but exposures to silica and other dusts were believed to account for many of these cases. The results of statistical analyses did not implicate RCF exposure  or yielded results only slightly suggestive of an RCF exposure effect .
In the 1996 evaluation of the European cohort, small opacities of category 1/0 or greater were positively associated with RCF exposures that occurred before 1971 . Ten of the 51 (19.6%) male workers exposed before 1971 developed category 1/0 or greater opaci-tiesC8 had also been exposed to asbestos and 9 were either current or ex-smokers.
Both the U.S.  and the European Burge et al. 1995;Cowie et al. 1999] studies found that occupational exposure to RCFs is associated with various reported respiratory symptoms and conditions, after adjusting for the effects of age, sex, and smoking. Exposure to RCF concentrations in the range of 0.2 to 0.6 f/cm 3 was associated with statistically significant increases in eye irritation (OR=2.16, 95% CI=1.32-3.54), stuffy nose (OR=2.06, 95% CI=1.25-3.39), and dry cough (OR=2.53, 95% CI=1.25-5.11) compared with exposure concentrations lower than 0.2 f/cm 3 . Increasing ORs were demonstrated for RCF exposure concentrations greater than 0.6 f/cm 3 compared with exposure concentrations 15 fiber-months/ cm 3 (that is, >1.25 fiber-years/cm 3 ) relative to exposure to 15 fiber months/cm 3 (dyspnea grade 1COR=2.1, 95% CI=1.3-3.3; dyspnea grade 2-OR=3.8, 95% CI=1.6-9.4). Lockey et al.  also found statistically significant associations between cumulative RCF exposure and chronic cough (OR=2.0, 95% CI=1.0-4.0) and pleurisy (OR=5.4, 95% CI=1.4-20.2). Lemasters et al.  also noted associations (P<0.05) between employment in an RCF production job and increased prevalence of dyspnea and the presence of at least one respiratory symptom or condition. Recurrent chest illness in the European cohort was associated with cumulative exposure to respirable fibers and was most strongly associated with cumulative exposure to respirable dust .
In cross-sectional analyses involving spirometric testing, both the U.S.  and 1986 European  studies found that cumulative RCF exposure was associated with pulmonary function decrements among current and former smokers. The 1996 European study demonstrated decrements in current smokers only . The observed decreased pulmonary function in the European workers remained significantly associated with cumulative RCF exposure, even after controlling for cumulative exposure to inspirable dust . A longitudinal analysis of data from multiple PFTs by Lockey et al.  led the researchers to conclude that exposures to RCFs between 1987 and 1994 were not associated with decreased pulmonary function. The findings from the U.S. and European studies suggest that decrements in pulmonary function observed in current and former smokers result from an interactive effect between smoking and RCF exposure.

# Carcinogenicity Risk Assessment Analyses
The literature contains three significant independent risk analyses of occupational exposure to RCFs and potential health effects. In each of these analyses, health effects data derived from multidose and MTD studies with rats were used with models to extrapolate risks to human populations. The modeling of effects observed in experimental animal studies was necessitated by the lack of adequate data on adverse health effects in humans with occupational exposures to RCFs. The three studies, described in detail below and in Table 5-9, include the following studies: Dutch Expert Committee on Occupational Standards (DE-COS) , Fayerweather et al. , and Moolgavkar et al. .

# DECOS 
In 1995, DECOS (a workgroup of the Health Council of the Netherlands) published a report evaluating the health effects of occupational exposure to SVFs. The purpose of the report was to establish health-based recommended occupational exposure limits for specific types of SVFs. As one of the criteria for determining the airborne exposure limits for six distinct types of SVFs, risk assessments were performed for each fiber type, including RCFs. The risk analysis for RCFs was based on the assumption that RCFs are a potential human carcinogen as indicated by the positive results of carcinogenicity testing with animals. A health-based recommended occupational exposure limit was determined using the following rationale:
1. If the carcinogenic potential of RCFs is caused by a nongenotoxic mechanism, an occupational exposure limit of 1 respirable f/cm 3 as an 8-hr TWA should be recommended based on an NOAEL of 25 f/cm 3 and a safety factor of 25.
2. If the carcinogenic potential of RCFs is linked to a genotoxic mechanism, a model assuming a linear relationship between dose and the response (cancer) should be used to establish the occupational exposure limit.
The model indicated that an excess cancer risk of 4 10 -3 is associated with a TWA exposure to 5.6 respirable f/cm 3 based on 40 years of occupational exposure. A cancer risk of 410 -5 is associated with exposure to 0.056 f/cm 3 , and a linear extrapolation indicated that occupational exposure to 1 respirable f/cm 3 as an 8-hr TWA for 40 years is associated with a cancer risk of 710 -4 .
The DECOS analysis relied on the data from a long-term multidose study with rats exposed to kaolin ceramic fibers . These data showed that exposure by inhalation to 25 f/cm 3 (3 mg/m 3 ) for 24 months produced a negligible amount of fibrosis (mean Wagner score of 3.2). Consequently, the Dutch committee viewed 25 f/cm 3 as the NOAEL for fibrosis. The report also notes that at the time of publication, no data existed from retrospective cohort mortality or morbidity and case-control studies of persons with occupational exposures to RCFs. The linear modeling approach in this analysis of the exposure-response relationship using the animal data does not take into consideration possible differences in dosimetry and lung burden between rats and humans.

# Fayerweather et al. 
Fayerweather et al.  conducted a study primarily focusing on the risk assessment of occupational exposures for glass fiber insulation installers. They performed risk analyses with several other types of SVFs, including RCFs. Only the analysis with RCFs is presented here. This analysis applied an EPA linearized multistage model (representing a linear nonthreshold dose-response) to data from rat multidose and MTD chronic inhalation bioassays  to determine exposures at which Ano significant risk@ occurs; i.e., no more than one additional cancer case per 100,000 exposed persons. Nonlinear models were also used for comparison: the Weibull 1.5-hit nonthreshold model (representing the nonlinear, nonthreshold dose-response curve) and Weibull 2-hit threshold model (representing the nonlinear, threshold dose-response curve). Fiber inhalation by rats was equated to humans by determining the fibers/daykg of body weight for the animals and using an exposure scenario of 4 hr/day (consistent with insulation installation workers= schedules), for 5 days/week and 50 weeks/year over 40 working years of a 70-year lifespan. RCFC interpreted the results of the analysis with the linearized multistage model to represent a risk of 3.810 -5 for developing lung cancer over the working lifetime at an exposure concentration of 1 f/cm 3 . Using the nonlinear models, estimates of nonsignificant exposures (i.e., a working lifetime exposure associated with no more than 1 additional cancer case/100,000 exposed persons) were 2 and 3 orders of magnitude higher. Conversely, the risk estimates for exposure to 1 f/cm 3 for a working lifetime were lower using the Weibull 1.5-hit nonthreshold and Weibull 2-hit threshold models.

# Moolgavkar et al. 
This report describes a quantitative assessment of the risk of lung cancer associated with occupational exposure to RCFs . A major premise underlying the risk assessment is that humans are equally susceptible to RCFs as rats, at the tissue level. The risk analysis was performed using data from two chronic inhalation bioassays of RCFs in male Fischer 344 rats . Dosimetry in the risk assessment was based on a fiber deposition and clearance model developed by Yu et al.  that was used to estimate the lung burdens of fibers in humans. The doseresponse model used for the risk assessment was the two-mutation clonal expansion model, commonly referred to as the Moolgavkar-Venzon-Knudson (MVK) model. The MVK model was fitted to the rat bioassay data to estimate the proportional increase in the rat lung tumor initiation rate in RCF-exposed rats, relative to the background initiation rate in nonexposed rats. An MVK model for human lung cancer was then created by fitting the model to the age-specific lung cancer incidence for either of two human cohorts. Finally, the human lung cancer rate for a given tissue dose was estimated by increasing the tumor initiation rate in the human model by the same proportional amount that an identical tissue dose would increase the initiation rate in the MVK model for rats. The assumption was made that, for any given tissue dose, the proportional increase in the lung tumor initiation rate (relative to the background rate) is the same in humans as in rats. The two human cohorts used for the human modeling were a nonsmoking American Cancer Society (ACS) cohort [Peto et al. 1992 The excess risk was also calculated for exposure concentrations of 0.75 f/cm 3 , 0.5 f/cm 3 , and 0.25 f/cm 3 . These risk estimates are presented in Table 5-10.
As shown in Table 5-10, the highest risk estimates at each of the three exposure concentrations are associated with the linear model, followed by the exponential model. The lowest risk estimates are associated with the quadratic model. At each exposure concentration, more conservative risk estimates are obtained for the ACS cohort than the Steel Industry cohort.
At the recommended exposure guideline established by the RCFC (0.5 f/cm 3 ), the highest risk estimate (linear model, Steel Industry cohort) is the MLE of 5.310 -4 or 5.3/10,000 (95% UCL=2.910 -3 ). At 0.5 f/cm 3 , the risk estimates for the steel industry cohort are roughly 1 order of magnitude (factor of 10) lower with the exponential model (MLE=7.310 -5 , 95% UCL= 9.110 -5 ), and 2 orders of magnitude lower using the quadratic model (MLE=3.510 -6 , 95% UCL=1.110 -5 ). At the lowest exposure concentration (0.25 f/cm 3 ), the highest risk estimate (Steel Industry cohort, linear model) was the MLE of 2.710 -4 (95% UCL=1.410 -3 ). Again, on average, the risk estimates from the 3 models using the steel industry cohort are 3 to 4 times higher than for corresponding model values with the ACS cohort.
The authors concluded that the risk estimates based on the two cohorts "represent bounds on risks likely to be seen in occupational cohorts." However, an occupational cohort is unlikely to share the nonsmoking status of the ACS cohort. Therefore, of the two human populations used for model fitting in the Moolgavkar et al.  risk assessment, the steel industry cohort may be the preferable cohort to use for estimating the risks from occupational exposures to RCFs.
The Moolgavkar et al.  report also indicates airborne fiber concentrations estimated to result in excess lifetime risk for cancer of 10 -4 (1 in 10,000) based on the approaches used by DECOS  and Fayerweather et al.  and using the MVK model for both the ACS cohort and the steel industry cohort. With the DECOS  linearized, nonthreshold model approach, an excess lifetime cancer risk of 10 -4 was calculated to result from a fiber concentration of 0.14 f/cm 3 . Using the linearized, multistage model approach described in Fayerweather et al. , a fiber concentration of 2.6 f/cm 3 was estimated to correspond to the excess lifetime cancer risk of 10 -4 . With the MVK exponential model, an excess lifetime cancer risk of 10 -4 was determined for fiber concentrations of 0.7 f/cm 3 for the Steel Industry cohort and 2.7 f/cm 3 for the ACS cohort .

# Discussion
The estimated lung fiber burden for dosimetry in the analysis by Moolgavkar et al.  is a methodological improvement over the risk assessment for RCFs by Fayerweather et al. , which was based solely on the inhaled fiber concentration. Modeling lung burden dosimetry should, in theory, compensate for the known differences between rats and humans in fiber deposition and clearance. Similarly, using an MVK model for dose-response estimation could compensate for differences in cell mutation and proliferation rates in rats and humans. However, some key parameter values in the MVK and lung dosimetry models are poorly known. For example, the dosimetry model for humans has been validated with only three human tissue samples taken from workers whose exposures to RCFs were not measured .
A review and comparison of risk modeling approaches for RCFs by Maxim et al.  describes the three models here as well as additional more sophisticated variations of quantitative risk analyses for RCFs. Using approaches such as benchmark dose modeling, Maxim et al.  produced RCF unit potency values ranging from 1.410 -4 to 7.210 -4 . A common weakness among all three of the risk analyses stems from uncertainty about possible differences in the sensitivity of human lungs to fibers, as compared with rat lungs. The possibility of such a difference is acknowledged in the report by Moolgavkar et al. , but the effect of this uncertainty on the risk estimates is not explored quantitatively. As an example, Pott et al.  estimated that in the case of asbestos fibers, humans are approximately 200-fold more sensitive than rats, on the basis of fiber concentration in air. Pott et al.  further noted that a crocidolite inhalation study that was negative in the rat resulted in a rat lung fiber concentration that was more than 1,000-fold greater than the fiber concentrations in the lungs of asbestos workers with mesotheliomas. In support of this analysis, results of a study by Rodelsperger and Woitowitz  led the authors to conclude that humans are at least 6,000 times more sensitive than rats to a given tissue concentration of amphibole fibers. Although amphibole asbestos fibers have physicochemical characteristics which differ from those of RCFs, these findings raise questions about using experimental animal data for predicting human health effects and assuming that target tissues in humans and rats are equally sensitive to RCF toxicity.
The lung cancer risk estimates for RCFs derived by Moolgavkar et al.  may also be underestimated for occupationally exposed workers because of several basic assumptions made in the lung tissue dosimetry. Tissue dosimetry modeling in the Moolgavkar et al.  risk assessment is based on the assumption that a worker is exposed to RCFs for 8 hr/day, 5 days/week, 52 weeks/year, from age 20 to 50 . An alternative analysis, in which the assumption was changed to 8 hr/day, 5 days/week, 50 weeks/year from age 20 to 60, was also described but not presented in detail. In both cases, the breathing rate for light work was assumed to be 13.5 liters/minute. Additional information might be gained from assuming an exposure period of 8 hr/day, 5 days/week, 50 weeks/year, from age 20 to 65, with a breathing rate matching the International Commission on Radiological Protection "Reference Man" value for light work, which is 20 liters/minute . In addition, the cumulative excess risk of lung cancer was calculated only through age 70 . This practice may underestimate the lifetime risk of lung cancer in the exposed cohort, since a substantial fraction of the cohort may be expected to survive beyond age 70. The excess risk might also be calculated in a competing-risks framework using actuarial methods until most or all of the cohort is presumed to have died because of competing risks (generally 85 years). Finally, risk estimates derived by Moolgavkar et al.  were based solely on data from studies with rats, ignoring data from studies of hamsters . Because 42% of the hamsters in these studies developed mesotheliomas, using this database for the risk assessment would produce higher estimates of risk than the analysis based on the rat data.
6 Discussion and Summary of Fiber Toxicity comparative measures of toxicity for different agents. RCFs implanted into the pleural and abdominal cavities of various strains of rats and hamsters have produced mesotheliomas, sarcomas, and carcinomas at the sites of fiber implantation . Similar tumorigenic responses have been observed following intratracheal instillation of RCFs . These data provide additional evidence of the carcinogenic effects of RCFs in exposed laboratory animals.
Epidemiological data have not associated occupational exposure to RCFs under current exposure conditions with increased incidence of pleural mesothelioma or lung cancer . However, in epidemiologic studies of workers in RCF manufacturing facilities , increased exposures to airborne fibers have been linked to pleural plaques, small radiographic parenchymal opacities, decreased pulmonary function, respiratory symptoms and conditions (pleurisy, dyspnea, cough), and skin and eye irritation.
Many of the respiratory effects showed a statistically significant association with RCF exposure after controlling or adjusting for potential confounders, including cigarette smoking and exposure to nonfibrous dust. Yet in PFTs, the interactive effect between smoking and RCF exposure was especially pronounced, based on the finding that RCF-associated decreases

# Significance of Studies with RCFs
Three major sources of data contributing to the literature on RCFs are (1) experimental studies with animals and in vitro bioassays, (2) epidemiologic studies of populations with occupational exposure to RCFs (primarily during manufacturing), and (3) exposure assessment studies that provide quantitative and qualitative measurements of exposures as well as the physical and chemical characteristics of airborne RCFs. Each of these sources of information is considered integral to this criteria document for providing a more comprehensive evaluation of occupational exposure to RCFs and their potential health consequences.
Data from inhalation studies with animals exposed to RCFs have demonstrated statistically significant increases in the induction of lung tumors in rats and mesotheliomas in hamsters .
Other inhalation studies with RCFs have shown pathobiologic inflammatory responses in lung and pleural tissues . Implantation and instillation methods have also been used in animal studies with RCFs to determine the potential effects of these fibers on target tissues. These studies have recognized limitations for interpreting results because the exposure techniques bypass the natural defense and clearance mechanisms associated with the normal route of exposure (i.e., inhalation). However, they are useful for demonstrating mechanisms of toxicity and in pulmonary function were limited to current and former smokers . The interactive effect between exposure to airborne fibers and cigarette smoke has been previously documented (e.g., Selikoff et al.  ). However, unlike male workers, nonsmoking female workers did show statistically significant decreases in PFT results associated with RCF exposure . Analyses of data from multiple PFT sessions  have led researchers to conclude that decreases in pulmonary function were more strongly influenced by the higher exposures to airborne RCFs that occurred in the past. This conclusion seems plausible, since historical air-sampling data indicate that airborne fiber concentrations were much higher in the first decades of RCF manufacturing and that former workers had potentially higher exposures.
Multiple studies have been performed to characterize the concentrations and characteristics of airborne exposures to RCFs in the workplace. Current and historical environmental monitoring data  indicate that airborne exposures to RCFs include fibers in the respirable size range (<3.5 m in diameter and <200 m long ). These exposures occur in primary RCF manufacturing as well as in secondary industries such as RCF installation and removal. Sampling data from studies of domestic, primary RCF manufacturing sites indicate that average airborne fiber concentrations have steadily declined by nearly 2 orders of magnitude over the past 2 decades. For example, Rice et al.  report a maximum exposure estimate of 10 f/cm 3 associated with an RCF manufacturing process in the 1950s, and Esmen et al.  measured average exposure concentrations ranging from 0.05 to 2.6 f/cm 3 in RCF facilities in the middle to late 1970s. Rice et al. .
Although the potential exists for exposure to respirable crystalline silica in the forms of quartz, tridymite, and cristobalite during work with RCFs, exposure monitoring data indicate that these exposures are generally low . Maxim et al.  report that many airborne samples of crystalline silica collected during the installation and removal of RCF products contain concentrations below the LOD, with average concentrations of respirable crystalline silica per measurable task ranging from 0.01 to 0.44 mg/m 3 (equivalent 8-hr TWA range=0.004 to 0.148 mg/m 3 ). Other studies have shown greater potential for exposure to respirable crystalline silica (especially in the form of cristobalite) during the removal of afterservice RCF materials . For processes associated with higher concentrations of airborne respirable fibers, there are also generally greater concentrations of total and respirable dusts .

# Factors Affecting Fiber Toxicity
To accurately interpret the results of experimental and epidemiologic studies with RCFs, it is important to consider recognized factors that contribute to fiber toxicity for RCFs and other SVFs in general. The major determinants of fiber toxicity have been identified as fiber dose (or its surrogate, airborne fiber exposure), fiber dimensions (length and diameter), and fiber durability (especially as it affects fiber biopersistence in the lungs) .

# Fiber Dose
The measurement of airborne fiber concentrations is frequently used as a surrogate for assessing dose and health risk to workers. Analyses of historical and current air sampling data indicate that occupational exposure concentrations of airborne RCFs have decreased dramatically in the manufacturing sector . In chronic inhalation studies of RCFs , both rats and hamsters were exposed to a range of size-separated RCF concentrations in a nose-only inhalation protocol. When airborne RCFs are generated, half or more of the aerosol is composed of respirable particles of unfiberized material that was formerly a component of the fiber . Because of the nature of this mixed exposure, it is difficult to determine the relative contributions of the airborne fibers and nonfibrous particulates to the adverse effects observed in humans and animals. It has been postulated that the nonfibrous particulates may have contributed to an overload effect in the Mast et al.  animal studies with RCFs . Burge et al.  have suggested that the health effects seen in RCF-exposed workers are a consequence of combined particulate and fiber exposure, but the decrements in lung function are more related to fiber exposure combined with smoking.
Other studies have shown that for processes associated with higher concentrations of airborne respirable fibers, there is also a greater concentration of total and respirable dust .

# Fiber Dimensions
Throughout the literature, studies support the theory that fiber toxicity is related to fiber dimensions . Initially, fiber dimensions (length and diameter) play a significant role in determining the deposition site of a fiber in the lungs. Longer and thicker (>3.5 m in diameter) fibers are preferentially deposited in the upper airways by the mechanisms of impaction  or interception. Timbrell  suggested that direct interception plays an important role in the deposition of fibers, as the fiber comes into contact with the airway wall and is deposited. Fibers being deposited in the larger ciliated airways are generally cleared via the mucociliary escalator. Thinner fibers tend to maneuver past airway bifurcations into smaller and smaller airways until their dimensions dictate deposition either by sedimentation or diffusion . Another factor that may enhance deposition is the electrostatic charge a fiber can accumulate during dust-generating processes in occupational settings . The fiber charge may affect its attraction to the lung surface, causing the fiber to be deposited by electrostatic precipitation.
Although the dimensional characteristics and geometry of a fiber influence its deposition in the respiratory tract, the fiber's length and chemical properties dictate its clearance and retention once it has been deposited within the alveolar region. For the fiber that traverses the respiratory airways and is deposited in the gas exchange region, possible fates include dissolution, clearance via phagocytic cells (alveolar macrophages) in the alveoli, or translocation through membranes into interstitial tissues. Both test animals and workers have been exposed to RCFs of similar length and diameter , and these exposures include fibers of respirable dimensions . Since rats and other rodents are obligate nasal breathers, fibers greater than about 1 m in diameter are too large for deposition in their alveoli . By comparison, humans can inhale and deposit fibers up to 3.5 m in diameter in the thoracic and gas exchange regions of the lung. This physiological difference prevents the evaluation of fibers with diameters of about 1 to 3.5 m (which would have human relevance) in rodent inhalation studies.
The role of fiber size in inducing biological effects is well documented and reviewed in the literature . Stanton et al.  hypothesized that glass fibers longer than 8 m with diameters thinner than 0.25 m had high carcinogenic potential. In a review of the significance of fiber size to mesothelioma etiology, Timbrell  concluded that the thinner fibers with an upper diameter limit of 0.1 m are more potent for producing diseases of the parietal pleura (e.g., mesothelioma and pleural plaques) than thicker fibers. That value for fiber diameter is cited by Lippmann  in his asbestos exposure indices for mesothelioma. Oberdorster  studied the effects of both long (>10-16 m) and short (<10 m) fibers on alveolar macrophage functions, concluding that both will lead to inflammatory reactions-although a distinct difference exists in the long-term effects because of differential clearance of fibers of different sizes. Alveolar macrophages constitute the first line of defense against particles deposited in the alveoli; they migrate to sites where fibers are deposited and phagocytize them. The engulfed fibers are then moved by the macrophages toward the mucociliary escalator and removed from the respiratory tract. The ability of the macrophages to clear fibers is size-dependent. Short fibers (<15 m long) can usually be phagocytized by one rat alveolar macrophage  have suggested that incomplete or frustrated phagocytosis may play a role in the increased toxicity of longer fibers. Fiber length has been correlated with the cytotoxicity of glass fibers , with greatest cytotoxicity for fibers 17 and 33 m long compared with shorter fiber samples. Long fibers (17 m average length) tend to be a more potent inducer of TNF production and transcription factor activation than short fibers (7 m average length) .
When comparing the dimensions of airborne fibers with those found in the lungs, it is important to consider the preferential clearance of shorter fibers as well as the effects of fiber dissolution and breakage. Yu et al.  evaluated these factors in a study that led to the development of a clearance model for RCFs in rat lungs. Results of that study confirmed that fibers 10 to 20 m long are cleared more slowly than those <10 m long because of the incomplete phagocytosis of long fibers by macrophages. The preferential clearance of shorter fibers has also been documented in studies with chrysotile asbestos and other mineral fibers, in which the average length of retained fibers increased during a discrete period following deposition . This increase might also be explained by the longitudinal cleavage pattern of asbestos fibers, which results in longer fibers of decreasing diameters . By contrast, any breakage of RCFs would occur perpendicular to the longitudinal plane, resulting in shorter fibers of the same diameter. For the clearance model developed by Yu et al. , the effect of fiber breakage was also assessed from experimental data and incorporated into the model. The authors concluded that the simultaneous effect of fiber breakage and differential clearance leads only to a small change in fiber size distribution in the lung. This result suggests that the dimensions of fibers in the lung are closely related to the dimensions of fibers measured in the airborne samples (adjusted for deposition); thus, most short fibers in the lungs originated as short fibers in airborne exposures.
The dimensions of airborne fibers have also been characterized for workers with occupational exposure to RCFs. One study of domestic RCF manufacturing facilities found that approximately 90% of airborne fibers were 10 m . Measurements of airborne fibers in the European RCF manufacturing industry are comparable: Rood  reported that all fibers observed were in the thoracic and respirable size range (i.e., diameter <3 m), with median diameters ranging 0.5 to 1.0 m and median lengths from 8 to 23 m. During removal of RCF products, Cheng et al.  found that 87% of airborne fibers were within the respirable size range, with fiber diameters ranging from 0.5 to 6 m (median diame-ter=1.6 m) and fiber lengths ranging from 5 to 220 m. Another study  of airborne fiber dimensions measured during installation and removal of RCF materials in industrial furnaces reported GM D values of 0.38 and 0.57 m, respectively.

# Fiber Durability
Biopersistence (and specifically the retention time of the fiber in the lungs) is considered to be an important predictor of fiber toxicity. Fiber solubility affects the biopersistence of fibers deposited within the lung and is a key determinant of fiber toxicity. Bender and Hadley  suggest that some of the important considerations of fiber durability include the following:
 Fiber size-particularly length as it relates to the dimensions of the alveolar macrophages  Fiber dissolution rate  Mechanical properties of the fibers, including partially dissolved and/or digested fibers  Overloading of the normal clearance mechanisms of the lung Bignon et al.  argue that fibers that are biopersistent in vivo and in vitro are more biologically active than less durable fibers.
The durability of RCFs  provides a basis for suggesting that these fibers might persist long enough to induce biological effects similar to those of asbestos. In vitro durability tests have shown RCFs to be highly resistant to dissolution in biologically relevant mixtures such as Gamble's solution . The persistence of RCFs in both the peritoneal cavity  and the lung  has been recognized in experimental studies. Hammad et al.  sacrificed rats exposed to either slag wool or ceramic fibers via inhalation at 5, 30, 90, 180, or 270 days after exposure. The lungs of the animals were ashed in a low-temperature asher, and the fiber content of the lungs was evaluated by PCM. The researchers found that 24% of the deposited RCFs persisted in the lungs of rats sacrificed 270 days following exposure. In the same study, the lungs of rats exposed to slag wool contained only 6% of the slag wool fibers 270 days after exposure compared with those sacrificed 5 days following inhalation. From these results, it was concluded that RCFs follow a clearance pattern of relatively durable fibers that persist, translocate, or are removed by some mechanism other than dissolution.
Similar results were obtained in the study by Mast et al. , which shows that RCFs are persistent in the lungs of rats exposed by inhalation. Specifically, compared with the fiber burden in the lungs of animals sacrificed 3 months after exposure (recovery), the lungs of animals sacrificed after 21 months of recovery contained approximately 20% of the deposited fibers. Of the retained fibers (measured with both SEM and TEM techniques) 54% to 75% had diameters <0.5 m, and more than 90% were 5 to 20 m long.
Researchers have suggested that fibers deposited in the gas exchange region with lengths less than the diameter of an alveolar macrophage are phagocytized and cleared via the mucociliary system or the lymph channels. Dissolution of fibers within the AlM occurs if the fibers are not resistant to the acidic intracellular conditions or a pH~5 . Fibers that are not engulfed by alveolar macrophages are subjected to a pH of 7.4 in the extracellular fluid of the lung. A study of SVF durability in rat alveolar macrophages reports that RCFs are much less soluble than glass wool and rock wool fibers based on the amounts of silicon (Si) and iron (Fe) dissolved from the fibers in vitro . RCFs in rat alveolar macrophage culture dissolved less than 10 mg Si/m 2 of fiber surface area and less than 1 mg Fe/m 2 of fiber surface area. Glass wool dissolved more than 50 mg Si/m 2 , and rock wool dissolved nearly 2 mg Fe/m 2 when measured over comparable time periods. However, degradation and dissolution of deposited RCFs may still occur, based on the findings of higher dissolution of aluminum (Al) from RCFs (0.8 to 2.4 mg Al/m 2 ) in alveolar macrophages than from the other SVFs . In another study, SEM analysis of fibers recovered from the lungs of rats 6 months after inhalation of RCFs revealed an eroded appearance, causing the researchers to conclude that dissolution of Si in the fibers is a plausible mechanism for long-term fiber clearance .
SVFs in general are less durable than asbestos fibers. RCFs are more durable than many other SVFs, with a dissolution rate somewhat higher than chrysotile asbestos. Under the extracellular conditions in the lung, chrysotile-the most soluble form of asbestos-has a dissolution rate of <1 to 2 ng/cm 2 /hr. RCFs have a similar dissolution rate of about 1 to 10 ng/cm 2 /hr under conditions experienced in pulmonary interstitial fluid. Other more soluble SVFs can be 10 to 1,000 times less durable . At the measured solubility rate, an RCF with a 1-m diameter would take more than 1,000 days to dissolve completely .

# Summary of RCF Toxicity and Exposure Data
In addition to the main determinants of fiber toxicity (dose, dimension, and durability), other factors such as elemental composition, surface area, and composition can also influence the toxicity of the fiber. Thus, it is difficult to predict a fiber's potential for human toxicity based solely on in vitro or in vivo tests. Based on consideration of these factors, the major findings from the RCF animal and human studies are as follows:
 Toxicologic evidence from experimental inhalation studies indicates that RCFs are capable of producing lung tumors in laboratory rats and mesotheliomas in hamsters . However, interpreting these studies with regard to RCF potency and its implication for occupationally exposed human populations is complicated by the issue of coexposure to fibers and nonfibrous respirable particulate.
 The durability of RCFs contributes to the biopersistence of these fibers both in vivo and in vitro .
 Cytotoxicity and genotoxicity studies indicate that RCFs -are capable of inducing enzyme release and cell hemolysis ,
-affect mediator release ,
-may decrease cell viability and inhibit proliferation ,
-affect cell viability and proliferation , and -may induce free radicals, micronuclei, polynuclei, chromosomal breakage, and hyperdiploid cells .
 Exposure monitoring results indicate that airborne fibers measured in both the manufacturing and end-use sectors of the RCF industry have dimensions that fall within the thoracic and respirable size ranges .
 Epidemiologic studies of workers in the RCF manufacturing industry report an association between increased exposures to airborne fibers and the occurrence of pleural plaques, other radiographic abnormalities, respiratory symptoms, decreased pulmonary function, and eye and skin irritation . Current occupational exposures to RCFs have not been linked to decreases in pulmonary function of workers .
 Worker exposure to airborne fiber in the RCF industry over the past 20 years or more have decreased substantially, reportedly as the result of increased hazard awareness and the design and implementation of engineering controls .
These observations warrant concern for the continued control and reduction of occupational exposures to airborne RCFs.

# Existing Standards and
Recommendations lengths 10 m for up to 10 hr/day during a 40-hr workweek. NIOSH also recommended that airborne concentrations determined as total fibrous glass be limited to a 5 mg/m 3 of air as a TWA. At that time, NIOSH concluded that exposure to glass fibers caused eye, skin, and respiratory irritation. NIOSH also stated that until more information became available, this recommendation should be applied to other SVFs.
The Agency for Toxic Substances and Disease Registry (ATSDR) calculated an inhalation minimal risk concentration of 0.03 f/cm 3 for humans based on extrapolation from animal studies . The Agency used macrophage aggregation, the most sensitive indicator of inflammation from RCFs, as the basis for this value. Calculation of this value is based on exposure assumptions for general public health that differ from those used in models for determining occupational exposure limits.
ACGIH proposed a TLV of 0.1 f/cm 3 as an 8-hr TWA for RCFs under its notice of intended changes to the 1998 TLVs . On further review, this concentration was revised to 0.2 f/cm 3 . ACGIH also classifies RCFs as a suspected human carcinogen (A2 designations) . On the basis of a weight-of-evidence carcinogenic risk assessment, the EPA  classified RCFs as a Group B2 carcinogen (probable human carcinogen based on sufficient animal data).
ACGIH and EPA designations are consistent with that of the International Agency for Research on Cancer (IARC), which classified Standards and guidelines for controlling worker exposures to RCFs vary in the United States.
Other governments and international agencies have also developed recommendations and occupational exposure limits that apply to RCFs. Table 7-1 presents a summary of occupational exposure limit standards and guidelines for RCFs.
Within the United States, the RCFC formally established a recommended exposure guideline of 0.5 f/cm 3 as an element of its product stewardship program known as PSP 2002, which was endorsed by OSHA as a 5-year voluntary program . As part of that program, the RCFC recommends that workers wear respirators whenever the workplace fiber concentration is unknown or when airborne concentrations exceed 0.5 f/cm 3 . This exposure guideline was established by the RCFC on October 31, 1997, and replaces the previous exposure guideline of 1 f/cm 3 set by the RCFC in 1991.
Before this agreement, the OSHA General Industry Standard was most applicable to RCFs, requiring that a worker's exposure to airborne dust containing <1% quartz and no asbestos be limited to an 8-hr PEL of 5 mg/m 3 for respirable dust and 15 mg/m 3 for total dust .
NIOSH has not previously commented on occupational exposure to RCFs. However, in addressing health hazards for another SVF (fibrous glass), NIOSH  recommended an exposure limit (REL) of 3 f/cm 3 as a TWA for glass fibers with diameters 3.5 m and ceramic fibers, including RCF, as "possibly carcinogenic to humans (Group 2B)"  determined that "RCFs may pose a carcinogenic risk for humans," and set a healthbased recommended occupational exposure limit of 1 f/cm 3 .
The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area published a review of fibrous dusts  classifying RCFs as category IIIA2, citing "positive results (for carcinogenicity) from inhalation studies (often supported by the results of other studies with intraperitoneal, intrapleural, or intratracheal administration)."
In the United Kingdom, the Health and Safety Commission of the Health and Safety Executive has established a maximum exposure limit for RCFs of 1.0 f/ml of air, with the additional advisory to reduce exposures to the lowest as reasonably practicable concentration based on the category 2 carcinogen classification for RCFs .
8 Basis for the Recommended Standard ditions (including dyspnea, wheezing, coughing, and pleurisy) observed in RCF workers to be adverse health effects associated with exposure to airborne RCFs .
An association between inhaling RCFs and fibrotic or carcinogenic effects has been documented in animals, but no evidence of such effects has been found in workers in the RCF manufacturing industry. The lack of such an association could be influenced by the small population of workers in this industry, the long latency period between initial exposure and development of measurable effects, the limited number of persons with extended exposure to elevated concentrations of airborne fibers, and declining occupational exposure concentrations. However, the evidence from animal studies suggests that RCFs should be considered a potential occupational carcinogen. This classification is consistent with the conclusions of ACGIH, EPA, DECOS, and IARC. (See discussion in Chapter 7.)
Given these considerations, the NIOSH objective in developing an REL for RCFs is to reduce the possible risk of lung cancer and mesothelioma. In addition, maintaining exposures below the REL will also help to prevent other adverse effects, including irritation of the skin, eyes, and respiratory tract in exposed workers. To establish an REL for RCFs, NIOSH took into account not only the animal and human health data but also exposure

# Background
In the Occupational Safety and Health Act of 1970 (Public Law 91-96), Congress mandated that NIOSH develop and recommend criteria for identifying and controlling workplace hazards that may result in occupational illness or injury. In fulfilling this mission, NIOSH continues to investigate the potential health effects of exposure to naturally occurring and synthetic airborne fibers. This interest stems from the results of research studies confirming asbestos fibers as human carcinogens. Significant increases in the production of RCFs during the 1970s and concerns about potential health effects led to experimental and epidemiological studies as well as worker exposure monitoring. Chronic animal inhalation studies demonstrated the carcinogenic potential of RCFs, with a statistically significant increase in the incidence of lung cancer or mesothelioma in two laboratory species-rats and hamsters . Evidence of pleural plaques observed in persons with occupational exposures to airborne RCFs is clinically similar to that observed in asbestos-exposed persons after the initial years of their occupational exposures to asbestos . NIOSH considers the discovery of pleural plaques in U.S. studies of RCF manufacturing workers to be a significant finding because the plaques were correlated with RCF exposure . In addition, NIOSH considers the respiratory symptoms and con-information describing the extent to which RCF exposures can be controlled at different workplaces. On the basis of this evaluation, NIOSH considers an REL of 0.5 f/cm 3 (as a TWA for up to 10 hr/day during a 40-hr workweek) to be achievable for most workplaces where RCFs or RCF products are manufactured, used, or handled. Maintaining exposures at the REL will minimize the risk for lung cancer and reduce the risk of irritation of the eyes and upper respiratory system. The residual risks of lung cancer at the REL are estimated to be 0.073 to 1.2 per 1,000 based on extrapolations of risk models from Moolgavkar et al.  and Yu and Oberdorster .
The risk for mesothelioma at the REL of 0.5 f/cm 3 is not known but cannot be discounted. Evidence from epidemiologic studies showed that higher exposures in the past resulted in pleural plaques in workers, indicating that RCFs do reach pleural tissue. Both implantation studies in rats and inhalation studies in hamsters have shown that RCF fibers can cause mesothelioma. Because of limitations in the hamster data, the risk of mesothelioma cannot be quantified. However, the fact that no mesothelioma has been found in workers and that pleural plaques appear to be less likely to occur in workers with lower exposures suggests a lower risk for mesothelioma at the REL.
Because residual risks of cancer (lung cancer and pleural mesothelioma) and irritation may exist at the REL, NIOSH further recommends that all reasonable efforts be made to work toward reducing exposures to less than 0.2 f/cm 3 . At this concentration, the risks of lung cancer are estimated to be 0.03 to 0.47 per 1,000 based on extrapolations of risk models from Sciences International , Moolgavkar et al. , and Yu and Oberdorster .
Maintaining airborne RCF concentrations at or below the REL requires the implementation of a comprehensive safety and health program that includes routine monitoring of worker exposures, installation and routine maintenance of engineering controls, and worker training in good work practices. To ensure that worker exposures are routinely maintained below the REL, NIOSH recommends that an AL of 0.25 f/cm 3 be part of the workplace exposure monitoring strategy to ensure that all exposure control efforts (e.g., engineering controls and work practices) are in place and working properly. The purpose of the AL is to indicate when worker exposures to RCFs may be approaching the REL. Exposure measurements at or above the AL indicate a high degree of certainty that concentrations of RCFs exceed the REL. The AL is a statistically derived concept permitting the employer to have confidence (e.g., 95%) that if exposure measurements are below the AL, only a small probability exists that the exposure concentrations are above the REL. When exposures exceed the AL, employers should take immediate action (e.g., determine the source of exposure, identify measures for controlling exposure) to ensure that exposures are maintained below the exposure limit. NIOSH has concluded that an AL allows for the periodic monitoring of worker exposures in the workplace so that resources do not need to be devoted to conducting daily exposure measurements. The AL concept has been an integral element of recommended occupational standards in NIOSH criteria documents and in comprehensive standards promulgated by OSHA and MSHA.

# Rationale for the REL
The recommendation to limit occupational exposures to airborne RCFs to a TWA of 0.5 f/cm 3 is based on data from animal and human studies, risk assessments, and the availability of methods to control RCF exposures at the REL in many workplaces. Establishing the REL for RCFs is consistent with the mission of NIOSH mandated in the Occupational Safety and Health Act of 1970. This Act states that NIOSH is obligated to "develop criteria dealing with toxic materials and harmful physical agents and substances which will describe exposure levels that are safe for various periods of employment, including but not limited to the exposure levels at which no employee will suffer impaired health or functional capacities or diminished life expectancy as a result of his work experience." The carcinogenicity findings from the chronic noseonly inhalation assays of RCF1 in rats and hamsters  warrant concern about possible health effects in workers exposed to RCFs. Although no increase in lung cancer or mesothelioma mortality has been observed in worker populations exposed to RCFs, radiographic analyses indicate an association between pleural changes (including pleural plaques) and RCF exposure  and the European [Trethowan et al. 1995;Burge et al. 1995;Cowie et al. 1999Cowie et al. , 2001 studies have found RCF-associated respiratory symptoms, pulmonary function reductions, and pleural abnormalities among RCF production workers.
Several independent evaluations have quantitatively estimated the risk of lung cancer for workers exposed to RCFs at various concentrations . NIOSH evaluated these studies to determine whether an appropriate qualitative or quantitative assessment of lung cancer risk could be achieved. In addition, exposure information was collected during the 5-year monitoring period covered under the consent agreement between RCFC and EPA . NIOSH used the exposure information to evaluate the feasibility of controlling workplace exposures at manufacturing and end-use facilities where RCFs and RCF products are handled.

# Carcinogenesis in Animal Studies
Chronic inhalation studies with RCFs demonstrate significant increases in the incidence of mesothelioma in hamsters and lung cancer in rats. Tables 8-1 through 8-4 present a synopsis of the major findings of these studies . Results from chronic animal inhalation studies with chrysotile and amosite are also presented (i.e., results for the positive control groups); these data provide a reference point for determining the relative toxicity of RCFs .
Chronic inhalation exposure to RCF1 at 30 mg/m 3 (187 WHO f/cm 3 ) induced a 13% (16/123) incidence of lung tumors in F344 rats . The incidence of lung cancer at lower doses did not show a statistically significant difference from the unexposed control group. Lung fiber burdens in the multidose chronic rat study revealed a dose-response relationship . In the rat, 16 mg/m 3 (120 WHO f/cm 3 ) appeared to be the NOAEL for lung cancer and 3 mg/m 3 (26 WHO f/cm 3 ) appeared to be the NOAEL for fibrosis. Although it has been suggested that fibrosis in animals is a precursor to carcinogenesis, a definite link has not been shown for RCFs or other fibers. No lung cancers were found in hamsters exposed to RCF1 .    Chronic inhalation exposure to RCF1 at 30 mg/m 3 induced a 41% (42/102) incidence of mesotheliomas in Syrian golden hamsters . Determining a dose-response relationship for inducing mesothelioma is not possible based on currently available data because of the single exposure dose tested in the hamster and because of the low, sporadic occurrence of mesothelioma in the exposed rats . Yet the occurrence of mesotheliomas in the rat and the high incidence in the hamster are biologically significant because the spontaneous incidence of mesotheliomas in rats and hamsters has historically been very low .
To assess the significance of the mesothelioma incidence observed in RCF-exposed hamsters, these results were compared with those obtained from hamsters that were exposed to chrysotile asbestos and were used as positive controls for the study  (see Tables 8-3 and 8-4). However, the chrysotileexposed hamsters failed to develop any tumors and therefore could not be considered true positive controls. Based on these results, a potency ranking could not be assigned for RCFs relative to chrysotile, since the carcinogenic response rate for the latter was zero in this study.
The two fibers tested also differed with regard to their dose and fiber dimension.
The McConnell et al.  study of hamsters exposed to amosite asbestos provides doseresponse data for comparison with the RCF1 data of McConnell et al.  (See Tables 8-3 and 8-4.). These separate studies examined the effects of RCF1 or amosite asbestos in hamsters using relatively similar exposure conditions, experimental conditions, and fiber dimensions . A concentration of 215 RCF1 WHO f/cm 3 induced mesotheliomas in 41% of hamsters . Interstitial and pleural fibrosis were first observed at 13 weeks following amosite asbestos exposure and at 6 months following RCF1 exposure. Although average fiber dimensions for the RCF1 and amosite asbestos samples were similar, the RCF1 sample contained a higher percentage of fibers longer than 20 m .
Results from a dose-response analysis using the mesothelioma data from the RCF and amosite asbestos hamster studies  (see Section 5.1.2). This analysis may not predict the mesothelioma risk in humans, since RCF1 contained a greater percentage of fibers longer than 20 m and because of differences in fiber durability. Amosite asbestos is a more durable fiber with a longer in vivo half-life than RCF1  (see Table 8-5). Yet RCFs are more durable and less soluble than many other types of SVFs that have not demonstrated carcinogenicity in experimental studies. This characteristic is significant, as the durability of asbestos and SVFs (including RCFs) may be linked to the risk of lung cancer in animals chronically exposed to these fibers . Because of the long latency period for the development of mesotheliomas in humans, Berry  hypothesized that fibers of sufficient durability are needed to cause this disease in humans. Extrapolation of the RCF dose-response data for lung cancer and mesothelioma in exposed rodents should take into account the durability of RCFs in humans. Some evidence indicates that rats are less sensitive than humans to the development of lung cancer and mesothelioma from exposure to asbestos and may therefore represent an inappropriate model for human risk assessment. Pott et al.  hypothesized that in chronic inhalation studies, rats may have a lower sensitivity to inorganic fiber toxicity than humans. The lung cancer risk from inhaling asbestos may be two orders of magnitude lower in rats than in humans, and the mesothelioma risk from inhaling asbestos may be three orders of magnitude lower for rats. Rodelsperger and Woitowitz  measured amphibole fiber concentration in the lung tissues of humans with mesothelioma and compared the results with fiber burdens reported in rats. A significantly increased OR (OR=4.8, 95%; CI=1.05-21.7) for mesothelioma was seen in humans with amphibole concentrations between 0.1 and 0.2 fiber/g of dried lung tissue. The lowest tissue concentration reported to produce a significant carcinogenic response in rat inhalation studies of amphiboles (specifically crocidolite) was 1,250 fibers/g of dried lung tissue. By comparing these results, Rodelsperger and Woitowitz  estimated that humans are at least 6,000 times more sensitive than rats to a given tissue concentration of amphibole fibers.
This work is refuted by other scientists who favor the rat as an appropriate model for evaluating the risk evaluation of lung cancer in humans . Limitations of the Rodelsperger and Woitowitz  and Pott  analyses (discussed earlier) include the lack of a dose-response analysis, analysis of only one epidemiologic study, inadequate comparisons of exposure duration, lack of accounting for the potentially multiplicative effect of smoking and asbestos exposure, lack of consideration of latency and clearance, and different fiber measurement techniques.
In summary, multiple factors affecting the comparability of different fiber types and animal models reported in the literature make it difficult to determine whether the carcinogenic potency of RCFs in animals is similar to that in humans. Extrapolation of the animal data to humans is further complicated by a limited understanding of the mechanisms of fiber toxicity. Consequently, any extrapolation of the cancer risk found in animals exposed to RCFs must account for differences between humans and rodents with regard to fiber deposition and clearance patterns, uncertainty about the role of RCF durability for potentiating an adverse effect, and possible species differences in sensitivity to fibers.

# Health Effects Studies of Workers Exposed to RCFs
Two major research efforts evaluated the morbidity of workers exposed to airborne fibers in the RCF manufacturing industry. One study was conducted in the United States and the other in Europe. The objective of each was to evaluate the relationship between occupational exposure to RCFs and potential adverse health effects. These studies contained multiple components including standardized respiratory and occupational history questionnaires, chest radiographs, pulmonary function tests of workers, and air sampling to estimate worker exposures. The first studies of European plants were conducted in 1986 and included current workers at seven RCF manufacturing plants . A followup cross-sectional study conducted in 1996 evaluated the same medical endpoints in workers from six of these seven European manufacturing plants (one plant had ceased operation) [Cowie et al. 1999[Cowie et al. , 2001. Current as well as former workers were included as study subjects in the followup study. The studies of U.S. plants began in 1987 and involved evaluations of current workers at five RCF manufacturing plants and former workers at two of the plants [Lemasters et al. 1994[Lemasters et al. , 1998[Lemasters et al. , 2003Lockey et al. 1993Lockey et al. , 1996Lockey et al. , 1998Lockey et al. , 2002. In the United States, the earliest commercial production of RCFs and RCF products began in 1953. In Europe, RCF production began in 1968. The demographics of the U.S. and European populations were similar at the time they were studied, but the average age and duration of employment for the U.S. workers were slightly higher than for the workforce in the 1986 European studies because of the earlier development of this industry in the United States.

# Pleural changes in humans
The radiographic analyses of the U.S. and 1996 European populations in RCF manufacturing detected an association between pleural changes and RCF exposure . In the initial European studies, Trethowan et al.  found pleural abnormalities in a small number of RCF workers who had other confounding exposures that did not include asbestos. Differences observed in pleural abnormalities between the U.S. and European worker populations may be related to the latency of exposure required to cause specific pleural changes , especially the formation of pleural plaques, which were first observed in studies of the U.S. RCF manufacturing industry, with its longer latency period. Historical air sampling data also indicate that airborne fiber concentrations were much higher in early U.S. RCF manufacturing. Therefore, in addition to their longer overall latency, RCF manufacturing workers in the United States probably had generally higher exposures in the early years of the industry than did their European counterparts. These factors might explain the appearance of RCF-associated pleural plaques in the U.S. studies before their detection in the European studies. The U.S. and 1986 European studies yielded little evidence of an association between radiographic parenchymal opacities and RCF exposure. In the U.S. study, small opacities were rare, with only three cases noted in one report  and only one case (with small rounded opacities of profusion category 3/2 attributable to prior kaolin mine work) noted in the other . Small opacities of profusion category 1/0 or greater were more frequent in the European study by Trethowan et al. , but confounding exposures were believed to account for many of these cases. The results of statistical analyses indicated either no association with RCF exposure  or an association slightly suggestive of an RCF exposure effect .
In a more comprehensive evaluation of the European study population, small opacities of category 1/0 or greater were positively associated with RCF exposures that occurred before 1971 .

# Respiratory symptoms, irritation, and other conditions in humans
In both the U.S.  and the European . Between the 0.2 to 0.6 f/cm 3 and >0.6 f/cm 3 RCF exposure groups, a statistically significant increase occurred in ORs for wheezing (P15 fiber-months/cm 3 (i.e., >1.25 fiber-year/cm 3 ) relative to cumulative exposure to 15 fiber-months/cm 3 (dyspnea grade 1-OR=2.1, 95% CI 1.3-3.3; dyspnea grade 2-OR=3.8, 95% CI 1.6-9.4) after adjusting for smoking and other potential confounders. Lockey et al.  also found a statistically significant association between cumulative RCF exposure and pleurisy (OR=5.4, 95% CI=1.4-20.2), and an elevated but nonsignificant association between cumulative RCF exposure and chronic cough (OR=2.0, 95% CI=1.0-4.0). Lemasters et al.  also noted associations (P<0.05) between employment in an RCF production job and increased prevalence of dyspnea and the presence of at least one respiratory symptom after adjusting the data for confounders. Recurrent chest illness in the European study population was associated with the estimated cumulative exposure to thoracic-sized fibers but was more strongly associated with estimated cumulative exposure to thoracic-sized dust [Cowie et al. 1999[Cowie et al. , 2001.
In cross-sectional analyses, both the U.S.  and the 1986 European  studies found that cumulative RCF exposure is associated with pulmonary function decrements among current and former smokers. Lemasters et al.  also found statistically significant deficits in pulmonary function measures for nonsmoking female workers. The decreased pulmonary function in the European study population remained significantly associated with cumulative RCF exposure, even after controlling for cumulative dust exposure . The 1996 European study found pulmonary function decrements only in current smokers  concluded that the more recent RCF concentrations occurring after 1987 were not associated with decreased pulmonary function; rather, decreases in pulmonary function were more closely related to typically higher concentrations that occurred before this time period. The U.S. and European studies suggest that decrements in pulmonary function observed primarily in current and former smokers are evidence of an interactive effect between smoking and RCF exposure. Moolgavkar et al.  derived risk estimates for lung cancer in humans on the basis of the results from the two chronic bioassays of RCFs in male Fischer 344 rats . Several models (linear, quadratic, exponential) were used to estimate and compare risks using reference populations comprised of either a nonsmoking ACS cohort or a cohort of steel workers not exposed to coke oven emissions (see Table 5-10 for risk estimates). The exponential model provided the best statistical fit of the data. The linear model provided the highest estimates of human lung cancer risks from exposure to RCFs when used with the referent steel workers cohort (considered to be most representative of workers exposed to RCFs because it includes blue collar workers who smoke). Lung cancer risk estimates were calculated using each model at exposure concentrations of 0.25 f/cm 3 , 0.5 f/cm 3 , 0.75 f/cm 3 , and 1.0 f/cm 3 . The RCF-related lung cancer risk determined from the linear model for the lowest concentration (0.25 f/cm 3 ) was 0.27/1,000 for the cohort of steel workers compared with 0.036/1,000 using the exponential model and 0.00088/1,000 for the quadratic model when using the same referent population.

# Carcinogenic Risk in Humans
The risk estimates incorporated multiple assumptions, including a human breathing rate of 13.5 L/min (considered light work) and multiple criteria for defining the length of time a worker could be exposed to RCFs over a working lifetime. Higher risk estimates could be expected if the assumptions more closely represented those used by NIOSH and OSHA:
(1) a human breathing rate of 20 L/min and (2) a worker exposure duration of 8 hr/day, 5 days/wk, 50 wk/yr, from age 20 to 65 with the risk calculated beyond age 70 (e.g., to age 85). Furthermore, the calculated risk estimates could be an underestimation of the lung cancer risk to humans because the models assumed that the tissue sensitivity to RCFs in the rat is equal to that in humans. Although the lung cancer risk estimates derived from the rat data are reason for concern, estimates of human risk for mesothelioma from the high incidence (41%) of mesothelioma in hamsters cannot be appropriately modeled since only a single exposure was administered in the study. Primarily on the basis of chronic animal inhalation studies , NIOSH concludes that RCFs are a potential occupational carcinogen. Furthermore, the evidence of pleural plaques Lockey et al. 1996] observed in persons with occupational exposures to airborne RCFs is clinically similar to that observed in asbestos-exposed persons after the initial years of their occupational asbestos exposures . NIOSH considers the discovery of pleural plaques in U.S. studies of RCF manufacturing workers to be a significant finding because the plaques were correlated with RCF exposure . In addition, NIOSH considers the respiratory symptoms and conditions (including dyspnea, wheeze, cough, and pleurisy)  in RCF workers to be adverse health effects that have been associated with exposure to airborne fibers of RCFs.
Insufficient evidence exists to document an association between fibrotic or carcinogenic effects and the inhalation of RCFs by workers in the RCF manufacturing industry though these effects have been demonstrated in animal studies. The lack of an observed association between RCF exposure and these effects among workers could be affected by one or more factors, including several relating to the study population: the relatively small cohort, the proportion of workers with short tenure relative to what might be expected (on the basis of an asbestos analogy) in terms of disease latency, and workers with limited cumulative exposures to RCFs.

# Controlling RCF Exposures in the Workplace
Table 8-6 summarizes exposure monitoring data collected by the RCFC under a consent agreement with the EPA . These data indicate that exposures to RCFs during 1993-1998 had an AM fiber concentration of about 0.3 f/cm 3 for manufacturing and nearly 0.6 f/cm 3 for end users. Maxim et al. [1997Maxim et al. [ , 1999a reported results for both manufacturing and end-use sectors in which airborne fiber concentrations through 1997 were reduced to an AM <0.3-0.6 f/cm 3 .
The exposure monitoring data collected as part of the RCFC/EPA consent agreement provide assurance that when appropriate engineering controls and work practices are used, airborne exposure to RCFs can be maintained for most functional job categories (FJCs) at the REL of 0.5 f/cm 3 . For many manufacturing processes, reductions in exposures have resulted from the improved ventilation, engineering or process changes, and product stewardship programs . These data provide the basis for the NIOSH determination that a REL of 0.5 f/cm 3 as a TWA can be achieved.
Although many RCF manufacturing and enduser job tasks have exposures to RCFs at concentrations below 0.5 f/cm 3 , exposure monitoring data also indicate that not all FJCs may be able to achieve these RCF concentrations consistently. FJCs that currently experience airborne AM fiber concentrations >0.5 f/cm 3 include finishing (manufacturing and end use) and removal (end use). Typical processing during finishing operations (e.g., sawing, drilling, cutting, sanding) often requires high-energy sources that tend to generate larger quantities of airborne dust and fibers. For RCF insulation removal, activities are performed at remote sites where conventional engineering controls and fixed ventilation systems are more difficult to implement. For some operations, such as removal of RCF insulation tiles from furnaces, the release of high airborne fiber concentrations can occur. However, removal of RCF insulation tiles is not routine and is generally accomplished in a short period of time. Workers almost universally wear PPE and respiratory protection during these job tasks .
NIOSH acknowledges that the frequent use of PPE, including respirators, may be required for some workers handling RCFs or RCF products. The frequent use of PPE may be required during job tasks for which (1) routinely high airborne concentrations of RCF (e.g., finishing, insulation removal) exist, (2) the airborne concentration of RCF is unknown or unpredictable, and (3) job tasks are associated with highly variable airborne concentrations because of environmental conditions or the manner in which the job task is performed. In all work environments where RCFs or RCF products are handled, control of exposure through the engineering controls should be the highest priority.

# Summary
The following summarize the relevant information used as the basis for the NIOSH assessment of occupational exposures to RCFs:
 Airborne concentrations of RCFs have been characterized as containing fibers of dimensions in the thoracic and respirable size ranges. RCFs are among the most durable types of SVFs. In tests of solubility, RCFs are nearly as durable as chrysotile asbestos but significantly less durable than amphibole asbestos fibers such as amosite.
 Chronic, nose-only inhalation studies with RCFs in animals show a statistically  Fiber concentrations were determined during monitoring performed over a 5-year period (1993)(1994)(1995)(1996)(1997)(1998) under the Refractory Ceramic Fibers Coalition/Environmental Protection Agency (RCFC/EPA) consent agreement. Concentrations were determined by NIOSH method 7400 "B" counting rules.
significant increased incidence of lung tumors in rats and pleural mesotheliomas in hamsters. These data support the NIOSH determination that RCFs are a potential occupational carcinogen.
 Epidemiologic studies of workers in the RCF manufacturing industry show an increased incidence of pleural plaques, respiratory symptoms (dyspnea and cough), skin and eye irritation, and decreased pulmonary function related to increasing exposures to airborne fibers. Some of these conditions are documented for exposure concentrations in a range as low as 0.2 to 0.6 f/cm 3 . Studies of workers exposed to airborne RCFs show no evidence of excess risk for lung cancer or mesothelioma. However, the inability to detect such an association could be because of (1) the low statistical power for detecting an effect, (2) the short latency period for most workers occupationally exposed, and (3) the historically low and decreasing fiber exposures that have occurred in this industry.
 Risk assessment analyses using data from chronic inhalation studies in rats indicate that the excess risk of developing lung cancer when exposed to RCFs at a TWA of 0.5 f/cm 3 for a working lifetime is 0.073 to 1.2/1,000. However, on the basis of the assumptions used in the risk analyses, NIOSH concludes that this risk estimate is more likely to underestimate than to overestimate the risk to RCFexposed workers. Reduction of the RCF TWA concentration to 0.2 f/cm 3 would reduce the risk for lung cancer to 0.03 to 0.47/1,000. OSHA attempts to set PELs for carcinogens that reflect an estimated risk of 1/1,000 but is limited by considerations of technologic and economic feasibility.
 RCF exposure data gathered under a consent agreement between RCFC and EPA, which included a 5-year comprehensive air monitoring program (1993)(1994)(1995)(1996)(1997)(1998), indicate that airborne exposure concentrations to RCFs have been decreasing. Monitoring results show that 75% to >95% of TWA exposure concentration measurements in all FJCs (with one exception) were below 1.0 f/cm 3 . In all but two of the eight FJCs, >70% of TWA measurements were below the RCFC recommended exposure guideline of 0.5 f/cm 3 . On the basis of the review of these data, NIOSH has concluded that the REL of 0.5 f/cm 3 can be achieved in most work places where RCFs or RCF products are manufactured or used.
 The combined effect of mixed exposures to fibers and nonfibrous particulates may contribute to increased irritation of the respiratory tract, skin, and eyes. Engineering controls and appropriate work practices used to keep airborne RCF concentrations below the REL should help to minimize airborne exposures to nonfibrous particulates as well. Because the ratio of fibers to nonfibrous particulate in airborne exposures may vary among job tasks, exposure monitoring should include efforts to characterize particulate composition and to control and minimize airborne fibers and nonfibrous particulate accordingly.
From the assessment described above and throughout this document, NIOSH concludes that on a continuum of fiber toxicity, RCFs relate more closely to asbestos than to fibrous glass and other SVFs and should be handled accordingly. NIOSH considers all asbestos types to be carcinogens and has established a REL of 0.1 f/cm 3 for airborne asbestos fibers. This value was determined on the basis of extensive human and animal health effects data and the recognized limits of analytical methods.
Recognizing that RCFs are carcinogens in animal studies and given the limitations in deriving an exposure value that reflects no excess risk of lung cancer or mesothelioma for humans, NIOSH recommends that every effort be made to keep exposures below the REL of 0.5 f/cm 3 as a TWA for up to 10 hr/day in a 40-hr workweek. These efforts will further reduce the risk for malignant respiratory disease and protect workers from conditions and symptoms deriving from irritation of the respiratory tract, skin, and eyes.
From the analysis of historical exposure data (see Chapter 4) and the exposure data collected as part of the RCFC/EPA consent agreement monitoring program (Table 8-6), NIOSH has determined that compliance with the REL for RCFs is achievable in most manufacturing and end-use job categories. Although routine attainment of TWA exposures below the REL may not currently occur at all job tasks, it does represent a reasonable objective that can be achieved through modification of the job task or the introduction or improvement of ventilation controls.
9 Guidelines for Protecting Worker Health  Establish procedures for reporting hazards and giving feedback about actions taken to correct them.
 Instruct workers about using safe work practices and appropriate PPE.
 Inform workers about practices or operations that may generate high concentrations of airborne fibers (such as cutting and sanding of RCF boards and other RCF products).
 Make workers who remove refractory insulation materials aware of the following:
-Their potential for exposure to respirable crystalline silica -Health effects related to this exposure -Methods for reducing their exposure -Types of PPE that may be required (including respirators)

# Labeling and Posting
Although workers should have received training about RCF exposure hazards and methods for protecting themselves, labels and signs serve as important reminders and provide warnings to workers who may not ordinarily work in the area. Employers should do the following:
 Post warning labels and signs about RCFassociated health risks at entrances and inside work areas where airborne concentrations of RCFs may exceed the REL.
The following guidelines for protecting worker health and minimizing worker exposures to RCFs are considered minimum precautions that should be adopted as a part of a site-specific safety and health plan to be developed and overseen by appropriate and qualified personnel.

# Informing Workers about Hazards

# Safety and Health Training Program
Employers should establish a safety and health training program for all workers who manufacture, use, handle, install, or remove RCF products or perform other activities that bring them into contact with RCFs. As part of this training program, employers should do the following:
 Inform all potentially exposed workers (including contract workers) about RCFassociated health risks such as skin, eye, and respiratory irritation and lung cancer.
 Provide MSDSs on site: -Make MSDSs readily available to workers.
-Instruct workers how to interpret information from MSDSs.
 Teach workers to recognize and report adverse respiratory effects associated with RCFs.
 Train workers to detect hazardous situations.
 State the need to wear appropriate respiratory protection and protective clothing in areas where airborne RCFs may exceed the REL.
 If respiratory protection is required, post the following statement:

# Engineering Controls
Engineering controls should be the principal method for minimizing exposure to RCFs in the workplace.

# Ventilation
Achieving reduced concentrations of airborne RCFs depends on adequate engineering controls such as local exhaust ventilation systems that are properly constructed and maintained. Local exhaust ventilation systems that employ hoods and ductwork to remove fibers from the workplace atmosphere have been used by RCF manufacturers. One example is a slotted-hood dust collection system placed over a mixing tank so that airborne fibers are captured and collected in a bag house with HEPA filters . Other types of local exhaust ventilation or dust collection systems may be used at or near dust-generating systems to capture airborne fibers. Band saws used in RCF manufacturing and finishing operations have been fitted with such engineering controls to capture fibers and dust during cutting operations and thereby reduce exposures for the band saw operator . Disc sanders fitted with similar local exhaust ventilation systems are effective in reducing airborne RCF concentrations during sanding of vacuum-formed RCF products . For quality control laboratories or laboratories where production samples are prepared for analyses, exhaust ventilation systems should be designed to capture and contain dust. For guidance in designing local exhaust ventilation systems, see Industrial Ventilation-A Manual of Recommended Practice, 25th edition , Recommended Industrial Ventilation Guidelines , and the OSHA ventilation standard .

# RESPIRATORS REQUIRED IN THIS AREA.
 Print all labels and warning signs in both English and the predominant language of workers who do not read English.
 If workers are unable to read the labels and signs, inform them verbally about the hazards and instructions printed on the labels and signs.

# Hazard Prevention and Control
Proper  Proper decontamination and waste disposal Additional engineering controls have been evaluated by the Bureau of Mines for minimizing airborne dust in underground mining operations and at industrial sand plants. These controls may also have applications for RCF finishing, installation, and removal operations. The use of air showers (also known as a canopy air curtain or an overhead air supply island) involves positioning an air supply over the head of a worker to provide a flow of clean, filtered air to the worker's breathing zone [Volkwein et al. 1982[Volkwein et al. , 1988. Proper design and evaluation are critical for ensuring that filtration is adequate to remove airborne fibers from the air supply. Also, selection of the air supply flow rate is important to make sure that the velocity delivered to the worker's breathing zone is sufficient to overcome cross drafts and maintain a clean air flow.

# Tool selection and modification
The RCFC has reported that using hand tools instead of powered tools can significantly reduce airborne concentrations of dust. However, hand tools often require additional physical effort and time, and they may increase the risk of musculoskeletal disorders. Employers should therefore use ergonomically correct tools and proper workstation design to avoid ergonomic hazards.
The additional physical effort required to use hand tools may also increase the rate and depth of breathing and may consequently affect the inhalation and deposition of fibers. For operations such as cutting, sawing, grinding, drilling, and sanding, the high level of mechanical energy applied to RCF products with power tools increases the potential for elevated concentrations of airborne fiber. Examples  of how airborne fiber concentrations are affected by the equipment used to process RCF products include the following:
 A test of hand sawing versus the use of a powered jigsaw showed an 81% reduction in concentrations of airborne dust generated.
 A comparison of hand sanding versus power sanding showed a 90% reduction in concentrations of airborne dust generated.
 When a light water mist is applied to the surface of a vacuum-formed board before sanding, airborne dust concentration is reduced by 89% for hand sanding and 88% for powered sanding.
 The use of a cork bore (core drill) versus an electric drill with a twist bit for cutting holes in RCF product forms reduces airborne dust concentrations by about 85%.

# Engineering controls for RCF finishing operations
Researchers at NIOSH have been working with industrial hygienists at RCFC member facilities to study the effectiveness of engineering controls designed and applied to RCF finishing operations. Because hand tools are not always a practical solution to manufacturing and enduse facilities requirements, engineering controls are being designed and evaluated for use with powered tools.
A joint project between NIOSH and RCFC was initiated in 1998 and involved investigating engineering controls for use with a pedestal belt/ disc sander [Dunn et al. 2000[Dunn et al. , 2004. These units are frequently used by the manufacturers as well as the customer facilities to produce vacuum-formed boards sized to the required dimensions. A continuous misting nozzle and simple local exhaust ventilation system were integrated for use on the pedestal sanding unit.
The mister consisted of a standard atomization nozzle that was set for a low-water flow rate to minimize part degradation. The local exhaust ventilation system used two hoods or pickup points with a total airflow of 700 ft 3 /min.
During production of vacuum-formed boards, these two controls reduced fiber concentrations in the breathing zone as follows:
% decrease in airborne fibers: These studies highlight the potential for significant reductions in worker exposure using well designed and maintained engineering controls, but their effectiveness needs to be validated in the field.
Disc

# Wet methods for dust suppression
Fiber counts are lower in more humid atmospheres. Examples of using water to suppress dust concentrations are described as follows:
 At one RCF textile facility, misters have been added above broad looms and tape looms to decrease fiber concentrations.
 Water knives are high-pressure water jets that are used to cut and trim edges of RCF blanket while suppressing dust and limiting the generation of airborne fibers.
 During the installation of RCF modules in a furnace, a procedure called tamping is typically performed. After modules are put in place on the furnace wall, the modules are compressed by placing a 1-ft length of 2-by 4-ft lumber against the modules and tapping it lightly with a hammer. The process helps ensure that the RCF modules are installed tightly in place. When a light water spray is applied to the surface of the modules before tamping, airborne fiber concentration is reduced by about 75% . The water is applied with a garden-type sprayer that is set on mist using about 1 gal of water/100 ft 2 of surface area. However, caution is advised regarding the dampening of refractory-linings during installation. The introduction of water can damage refractory-lined equipment during heating with explosive spalling from the generation of steam.
 After-service RCF insulation removed from furnaces may be wetted to reduce the release of fibers.

# Isolation
Some manufacturing processes may be enclosed to keep airborne fibers contained and separated from workers.
 When possible, isolate workers from direct contact with RCFs by using automated equipment operated from a closed control booth or room.
 Maintain the control room at greater air pressure than that surrounding the process equipment so that air flows out rather than in.
 Make sure workers take special precautions (such as using PPE) when they must enter the general work area to perform process checks, adjustments, maintenance, assembly-line tasks, and related operations.

# Product Reformulation
One factor that contributes to the toxicity of an inhaled fiber is the durability of the fiber and its resistance to degradation in the respiratory tract. The chemical characteristics of RCFs make them one of the most durable types of SVFs. As a result, an inhaled RCF of specific dimensions will persist longer in the lungs. Modifying the physical characteristics of RCFs or reformulating their chemistry to produce less durable fibers are recommended options for reducing the hazard for exposed workers. Such an approach has been taken by one RCF manufacturer in developing two more soluble types of SVF . However, caution is advised for developing and distributing such modified fibers. Possible adverse health effects of newly developed fibers should be evaluated before introducing them into commerce. Appropriate testing of these fibers should be performed to provide information about the fiber toxicology and potential adverse health effects associated with exposure to these fibers.

# Work Practices and Hygiene
Use good work practices to help reduce exposure to airborne fibers. These practices include the following:
 Limit the use of power tools unless they are equipped with local exhaust or dust collection systems. When possible, use hand tools, which generate less dust and fewer airborne particles.
 Use HEPA-filtered vacuums, wet sweeping, or a properly enclosed wet vacuum system for cleaning up dust containing RCFs.
 During removal of RCF products, dampen insulation with a light water spray to keep fibers and dust from becoming airborne.
 Clean work areas regularly with HEPAfiltered vacuums or with wet sweeping methods to minimize the accumulation of debris.
 Limit access to areas where workers may be exposed to airborne RCFs: permit only workers who are essential to the process or operation.
Use good hygiene and sanitation to protect workers as well as people outside the workplace who might be contaminated with takehome dust and fibers:
 Do not allow workers to smoke, eat, or drink in work areas where they contact RCFs.
 If RCFs get on the skin, wash with warm water and mild soap.
 Apply skin moisturizing cream as needed to avoid dryness or irritation from repeated washing.
 Vacuum contaminated clothes with a HEPA-filtered vacuum before leaving the work area.
-Do not use compressed air to clean the work area or clothing.
-Do not shake clothes to remove dust.
 Do not wear contaminated clothes outside the work area. Instead, take the following measures to prevent taking contaminants home:
-Change into street clothes before going home.
-Leave contaminated clothes at the workplace to be laundered by the employer.
-Store street clothes in separate areas of the workplace to keep from contaminating them.
 Provide workers with showers and have them shower before leaving work.
 Prohibit removal of contaminated clothes or other items from the workplace .

# Personal Protective Equipment
Wear long sleeves, gloves, and eye protection when performing dusty activities involving RCFs.

# Respiratory Protection
NIOSH recommends using a respirator for any task involving RCF exposures that are unknown or have been documented to be higher than the NIOSH REL of 0.5 f/cm 3 (TWA). Respirators should not be used as the primary means of controlling worker exposures. Instead, NIOSH recommends using other exposure-reduction methods, such as product substitution, engineering controls, and changes in work practices. However, respirators may be necessary when available engineering controls and work practices do not adequately control worker exposures below the REL for RCFs. NIOSH recognizes this control to be a particular challenge in the finishing stages of RCF product manufacturing as well as during the installation and removal of RCF insulation materials.
If respiratory protection is needed, the employer should establish a comprehensive respiratory protection program as described in the OSHA respiratory protection standard . Elements of a respiratory protection program should be established and described in a written plan that is specific to the workplace. This respirator program must include the following:  At a minimum, use a half-mask, airpurifying respirator equipped with a 100 series particulate filter (this respirator has an assigned protection factor (APF) of 10.
 For a higher level of protection and for prevention of facial or eye irritation, use a full-facepiece, air-purifying respirator (equipped with a 100 series filter) or any powered, air-purifying respirator equipped with a tight-fitting full facepiece.
 For greater respiratory protection when the work involves potentially high airborne fiber concentrations (such as removal of after-service RCF insulation such as furnace insulation), use a supplied-air respirator equipped with a full facepiece, since airborne exposure to RCFs can be high and unpredictable.
A comprehensive assessment of workplace exposures should always be performed to determine the presence of other possible contaminants (such as silica) and to ensure that the proper respiratory protection is used.  exposure to airborne RCFs, perform the exposure sampling survey as follows:
 Collect representative personal samples for the entire work shift using NIOSH Method 7400 (B rules) .
 Perform periodic sampling at least annually and whenever any major process change takes place or another reason exists to suspect that exposure concentrations may have changed.
 Collect all routine personal samples in the breathing zones of the workers.
 For workers exposed to concentrations above the REL, perform more frequent exposure monitoring until at least two consecutive samples indicate that the worker's exposures no longer exceed the REL.
 Notify all workers about monitoring results and any actions taken to reduce their exposures.
 Make sure that any sampling strategy considers variations in work and production schedules as well as the inherent exposure variability in most workplaces . Similar exposure monitoring strategies have been espoused by the American Industrial Hygiene Association, which recommends that if measured exposures are less than 10% of the designated exposure limit (for example, REL or PEL), there is a high degree of certainty that the exposure limit will not be exceeded.

# Action Level

# Sampling Strategies
When sampling to determine whether worker exposures are below the REL, a focused sampling strategy may be more practical than random sampling. A focused sampling strategy targets workers perceived to have the highest exposure concentrations . A focused strategy is most efficient for identifying exposures above the REL if maximum-risk workers and time periods are accurately identified. Focused sampling may help identify short-duration tasks involving high airborne fiber concentrations that could result in elevated exposures over a full work shift.
Sampling strategies such as those used by Corn and Esmen , Rice et al. , and Maxim et al.  have been derived and used in RCF manufacturing facilities to monitor airborne fiber concentrations by selecting representative workers for sampling. The representative workers are grouped according to dust zones, uniform job titles, or functional job categories. These approaches are intended to reduce the number of required samples while increasing the confidence of identifying workers at similar risk.
Area sampling may also be useful in exposure monitoring for determining sources of airborne RCF exposures and assessing the effectiveness of engineering controls.

# Medical Monitoring
NIOSH recommends periodic medical evaluation, or medical monitoring, of RCF-exposed workers to identify potential health effects and symptoms that may be related to contact with airborne fibers. The following sections describe the objectives of medical monitoring and the elements of a medical monitoring program for workers exposed to RCFs.
The primary goals of a workplace medical monitoring program are (1) early identification of adverse health effects that may be related to exposures at work and (2) possible health trends within groups of exposed workers. These goals are based on the premise that early detection, subsequent treatment, and workplace interventions will ensure the continued health of the affected workforce.

# Objectives of Medical Monitoring
Medical monitoring and resulting interventions represent secondary prevention and should not replace primary prevention efforts to minimize worker exposures to RCFs. In the case of RCFs, medical monitoring is especially important because achieving compliance with the REL of 0.5 f/cm 3 does not assure that all workers will be free from the risk of respiratory irritation or chronic respiratory disease caused by occupational exposure. Early identification of respiratory system changes and symptoms associated with RCF exposures (such as decreased pulmonary function, irritation, dyspnea, chronic cough, wheezing, and pleural plaques) may signal the need for more intensive medical monitoring and the assessment of existing controls to minimize the risk of longterm adverse health effects. An ongoing medical monitoring program also serves to inform workers of potential health risks and promotes an understanding of the need for and support of exposure control activities.
A medical monitoring program serves as an effective secondary prevention method on two levels-screening and surveillance. Medical screening in the workplace focuses on the early detection of health outcomes for individual workers and may involve an occupational history, medical examination, and application of specific medical tests to detect the presence of toxicants or early pathologic changes before the worker would normally seek clinical care for symptomatic disease. By contrast, medical surveillance (described in Section 9.5) involves the ongoing evaluation of the health status of a group of workers through the collection and aggregate analysis of health data for the purpose of preventing disease and evaluating the effectiveness of intervention programs.

# Criteria for Medical Screening
To determine whether tests or procedures for medical screening are appropriate and relevant to a given hazard (in this case, exposure to airborne RCFs), the following factors should be considered:

# Recommended Program Elements
Recommended elements of a medical monitoring program for workers exposed to RCFs include provisions for an initial medical examination and periodic medical examinations at regularly scheduled intervals. Depending on the findings from these examinations, more frequent and detailed medical examinations may be necessary. Worker education should also be included as a component of the medical monitoring program. Specific elements of the examinations and scheduling are described below and illustrated in the flow chart diagram in Figure 9-1.

# Initial medical examination
An initial (baseline) examination should be performed as near as possible to the date of beginning employment (within 3 months). The initial medical examination should include the following:   If time since first RCF exposure is <10 years, examinations should be conducted at least every 5 years.  If time since first RCF exposure is 10 years, then examinations should be conducted at least every 2 years.
 A
 For workers with 10 or more years since first exposure to RCFs, periodic examinations should be conducted at least once every 2 years.
A chest X-ray and spirometric testing are important upon initial examination and may also be appropriate medical screening tests during periodic examinations for detecting respiratory system changes-especially in workers with more than 10 years since first exposure to RCFs. The value of periodic chest X-rays in a medical monitoring program should be evaluated by a qualified health care provider in consultation with the worker to assess whether the benefits of testing warrant the additional exposure to radiation. As with the frequency of periodic examinations, the utility of the chest X-ray as a medical test becomes greater for workers with more than 10 years since first exposure to RCFs (based on the latency period between first exposure and appearance of noticeable respiratory system changes). Because persons with advanced fiber-related pleural changes experience difficulty in breathing as the parietal and visceral surfaces become adherent and lose flexibility, it may prove beneficial to detect fibrotic changes in the early stages so steps may be taken to prevent further lung damage. Similar recommendations have been made for asbestos-exposed workers diagnosed with pleural fibrosis or pleural plaques to prevent more serious types of respiratory disease .

# More frequent medical examinations
Any worker should undergo more frequent and detailed medical evaluation if he or she has any of the following indications:
 New or worsening respiratory symptoms or findings (for example, chronic cough, difficulty breathing, wheezing, reduced

# Employer Actions
The employer should assure that the qualified health care provider=s recommended restrictions of a worker=s exposure to RCFs or to other workplace hazards are followed and that the REL for RCFs is not exceeded without requiring the use of PPE. Efforts to encourage worker participation in the medical monitoring program and to report symptoms promptly to the program director are essential for the program=s success. Medical evaluations performed as part of the medical monitoring program should be provided by the employer at no cost to the participating workers. If the recommended restrictions determined by the medical program director include job reassignment, such reassignment should be implemented with the assurance of economic protection for the worker. When medical removal or job reassignment is indicated, the affected worker should not suffer loss of wages, benefits, or seniority.
The employer should ensure that the medical monitoring program director communicates regularly with the employer=s safety and health personnel (such as industrial hygienists), employee representatives, and safety and health committees to identify work areas that may require evaluation and implementation of control measures to minimize the risk from exposure to hazards.

# Surveillance of Health Outcomes
Standardized medical screening data should be periodically aggregated and evaluated by an epidemiologist or other knowledgeable person to identify patterns of worker health that may be linked to work activities and practices that require additional primary prevention efforts. Routine aggregate assessments of medical screening data should be used in combination with evaluations of exposure monitoring data to identify changes needed in work areas or exposure conditions.
One example of surveillance using analyses of medical screening data is the ongoing epidemiologic study of RCF workers described in the RCFC product stewardship plan referred to as PSP 2000. Elements of this plan may be adapted and modified by other employers to develop medical surveillance programs for workers who are potentially exposed to RCFs. The research strategy also considers the usefulness of integrating fiber data from various scientific disciplines (toxicology, epidemiology, industrial hygiene, occupational medicine) to elucidate the characteristics of fibers.

# Smoking Cessation
In addition, NIOSH recommends that the following steps be taken with regard to RCF research:
1. Conduct basic scientific investigations, including in vitro and in vivo animal studies, to delineate the mechanism of action for RCF toxicity.
2. Conduct comparable studies for other SVFs and natural fibers so that the mechanistic data can be compared. For instance, Coffin et al.  examined the ability of different synthetic and natural fibers to induce mesotheliomas. They suggested that in addition to fiber length and width, currently undefined intrinsic surface characteristics of the fibers are directly related to their mesothelioma induction potency.     human pulmonary cells. The human alveolar macrophage has a volume several times greater than that of the rat alveolar macrophage . Macrophage size and volume may affect (1) the size range of fibers that can be phagocytized, dissolved, and cleared by the lungs and (2) the resulting pathogenicity of the fiber. Even the use of a human lung cell line does not guarantee that in vitro results will be directly applicable to the intact human response. The in vivo integration of stimuli from the nervous, hormonal, and cardiovascular systems cannot be reproduced in vitro.
Another point to consider when reviewing these data is the number and definitions of variables used in different studies. Variables include differences in fiber type, fiber length, fiber dose, cell type, and length of exposure tested, among others. Disparate results between studies make strong conclusions from in vitro studies difficult. At the same time, these studies may provide important data regarding the mechanism of action of RCFs that would not be obtainable in other testing venues.
RCFs may exert their effects on pulmonary target cells via direct or indirect mechanisms. Direct mechanisms are the resultant effects when fibers come in direct physical contact with cells. Direct cytotoxic effects of RCFs include effects on cell viability, responses, and proliferation.
The cellular and molecular effects of RCF exposures have been studied with two different objectives. One purpose of these in vitro studies is to provide a quicker, less expensive, and more controlled alternative to animal toxicity testing. These experiments, which strive to act as screening tests or alternatives to animal studies, are best interpreted by comparing their results with those of in vivo experiments. The second objective of in vitro studies is to provide data that may help to explain the pathogenesis and mechanisms of action of RCFs at the cellular and molecular levels. These cytotoxicity and genotoxicity studies are best interpreted by comparing the effects of RCFs with those of other SVFs and asbestos fibers. In vitro studies serve as an important complement to animal studies and provide important tools for studying the molecular mechanisms of fibers. It is not yet possible to use these data in the derivation of an REL.
Drawing strong conclusions relevant to human health based on these in vitro studies is impossible. One point to consider when reviewing these data is the relevance of the cell types studied.
Many studies to date have examined the effects of RCFs on rodent cell lines. The cytotoxic effects of RCFs may vary with cell size, volume, and lineage. Effects observed in the cells from organs other than the lung or effects in species other than the human may not be similar to those elicited with Indirect cellular effects of RCFs involve the interaction of fibers with inflammatory cells that may be activated to produce inflammatory mediators. These mediators may affect target cells directly or may attract other cells that act on target cells. An inflammatory cell type often used in RCF in vitro studies is the pulmonary macrophage. Pulmonary macrophages are the first line of defense against inhaled material that deposits in the alveoli, and among functions, they attempt to phagocytize particles deposited in the lung. Effects of RCF exposure on macrophages and other inflammatory cells are assessed by the measurement of inflammatory mediator release in vitro.
Three important groups of inflammatory mediators are cytokines, ROS, and lipid mediators (prostaglandins and leukotrienes). Some of the cytokines that have been implicated in the inflammatory process include TNF and interleukins (ILs). TNF and many ILs stimulate the deposition of fibroblast collagen, an initial step in fibrosis, and prostaglandins (PG)s inhibit these effects. ROS include hydroxyl radicals, hydrogen peroxide, and superoxide anion radicals. Oxidative stress occurs when the ROS level in a cell exceeds its antioxidant level. Oxidative stress may result in damage to deoxyribo nucelic acid (DNA), lipids, and proteins.
Either direct or indirect effects of RCFs may result in genotoxic effects on pulmonary target cells. Changes in the genetic material may be important in tumor development . Genotoxic effects may be assessed through the analysis of chromosome changes or alterations in gene expression following exposure to RCFs.
The following summary of RCF in vitro studies examines their direct effects on cell proliferation and viability and indirect effects via release of TNF, ROS, and other inflammatory mediators. The genotoxic effects of RCFs are also examined and summarized.  Luoto et al.  evaluated the effects of RCFs, quartz, and several MMVFs on LDH levels in rat alveolar macrophages and hemolysis in sheep erythrocytes. RCF1, RCF2, RCF3, and RCF4 at 1.0 mg/ml induced a lower release of LDH (less than 20% of control) from rat alveolar macrophages compared with quartz (approximately 40% of control) . RCF1 stimulated the lowest amount of MMVF10 fibers in hamster tracheal epithelial cells at 24 hr; no necrosis was present at 72 hr.
RCF1, RCF2, RCF3, and RCF4 as well as asbestos and other fibers had a dose-dependent effect on cytotoxicity, as measured by cell detachment, in the human alveolar epithelial cell line A549 . Cell detachment is associated with epithelial damage, an important step in the inflammatory process. These cells are a primary target of inhaled fibers. When equivalent doses (10, 25, 50, and 100 g/ ml) were tested with various fibers, all RCFs had a less significant effect than both crocidolite and amosite asbestos. When the dose data were adjusted for the number of fibers, RCF1, RCF2, and RCF3 were more cytotoxic than RCF4 and crocidolite.
In an assay determining the ability of fibers to induce an increase in the diameter of human A549 cells, an elutriated ceramic fiber (unspecified type) had a midrange of activity when compared with 12 other fibers . It was more active than most varieties of amosite tested (but not UICC amosite) but less active than the chrysotile fibers. An association was found between increasing length and assay activity. When these same fiber samples were tested for colony inhibition in V79/4 Chinese hamster lung fibroblasts, the ceramic fiber had even less effect than the TiO 2 control. Analysis of all fibers upheld the association between increasing length and increased activity. In both assays, fiber diameter was not related to activity in most cases.
Chrysotile asbestos at 10 g/cm 2 and crocidolite asbestos at 5 g/cm 2 altered porcine aortic endothelial cell morphology and increased neutrophil adherence . RCF1 fibers at 10 g/cm 2 did not change cell morphology or increase neutrophil binding.
These studies suggest that RCFs may have some similar direct cytotoxic effects to asbestos. They are capable of inducing enzyme release and cell hemolysis. They may decrease cell viability and inhibit proliferation. In most studies, the effects of RCFs are much less pronounced than the effects of asbestos at similar gravimetric concentrations. Fiber length was demonstrated to be an important factor in determining the cell responses in many studies.

# C.2 Indirect Effects of RCFs: Effects on Inflammatory Cells
In addition to direct effects on target cells, RCFs may have indirect mechanisms of action by acting on inflammatory cells. Inflammatory cells, such as pulmonary macrophages, may respond to fiber exposure by releasing inflammatory mediators that initiate the process of pulmonary inflammation and fibrosis. Cytokines and ROS are among the inflammatory mediators released. Many studies, summarized below and in Table C-2, have investigated this link between fiber exposure and mediator release to try to elucidate the mechanism of action of RCFs. Cytokines are a class of proteins that are involved in regulating processes such as cell secretion, proliferation, and differentiation. One of the cytokines most commonly analyzed in RCF cytotoxicity studies is TNF. TNF has been implicated in silica-and asbestos-induced pulmonary fibrosis . TNF and many ILs are associated with collagen deposition (an initial stage of fibrosis), and PGs inhibit these effects. Experiments on the effects of RCF exposure on TNF production in various cell types have had differing results.
TNF secretion has been associated with exposure to asbestos both in vitro and in vivo  . In vitro incubation of human alveolar macrophages from normal volunteers with 25 g/ml chrysotile asbestos resulted in increased levels of TNF secretion. Alveolar macrophages from 6 human subjects occupationally exposed to asbestos for more than 10 years secreted increased amounts of the cytokines TNF, IL-6, PGE 2 , and IL-1 in vitro. Five human subjects occupationally exposed for less than 10 years did not show increases in these cytokines. The two exposure groups were matched for age, smoking history, and diagnosis. The increased TNF secretion in both in vitro and chronic in vivo asbestosexposed conditions suggests its importance in the response of the lung to fiber exposure, although the small exposure group sizes warrant caution in drawing strong conclusions.
When equal numbers (8.2  10 6 ) of various fiber types, including RCF1, RCF2, RCF3, and RCF4, were incubated separately with rat alveolar macrophages, silicon carbide whiskers, amosite, and crocidolite asbestos stimulated the highest TNF release . RCF1, RCF2, RCF3, and RCF4 showed no significant increase in TNF release compared with control.
In contrast, ceramic fibers (unspecified type) at 50 g/ml (1.72  10 5 f) significantly increased TNF release compared with controls in rat alveolar macrophages . Potassium octatitanate whisker, chrysotile, and crocidolite asbestos induced the greatest TNF release. Alveolar macrophages exposed to either 300 or 1,000 g/ml RCFs or 1,000 g/ml asbestos showed a significant increase in TNF production . At 300 g/ml RCFs, a significant elevation occurred in leukotriene B 4 . At 1,000 g/ml RCFs, significant elevations occurred in leukotriene B 4 and prostaglandin E 2 . Levels induced at lower doses were not different from controls. At equivalent doses, the effect on the levels of all mediators measured was greater after asbestos exposure than after RCF exposure.
Chrysotile A, chrysotile B, crocidolite, MMVF21, RCF1, and silicon carbide at 100 g/ml caused a significantly increased synthesis of TNF mRNA after 90 minutes of incubation with rat alveolar macrophages . After 4 hr of incubation, chrysotile A still had a significantly increased TNF mRNA production, and all other fibers were at baseline concentrations.
None of the fibers studied increased TNF release at 90 minutes. However, an increased TNF bioactivity occurred after 4 hr of incubation with chrysotile A, chrysotile B, crocidolite, or MMVF21. RCF1 at 100 g/ml did not increase TNF production under these conditions.
Chrysotile asbestos and alumina silicate ceramic fibers increased in vitro alveolar macrophage TNF production in rats exposed to cigarette smoke in vivo and in rats unexposed to smoke . Asbestos at 50 and 100 g/ml induced a significantly greater TNF release in rats exposed to cigarette smoke versus unexposed rats. No significant differences were found between groups at all doses of RCF fibers tested (25, 50 and 100 g/ml). RCF exposure, in contrast to chrysotile, did not have a significant synergistic effect with cigarette smoke exposure.
In addition to the cytokines such as TNF, another group of inflammatory mediators that has been studied in vitro are the ROS. These mediators, also referred to as reactive oxygen metabolites (ROMs) are normally produced during the process of cellular aerobic metabolism and in phagocytic cells in response to particle exposure. One molecular effect of asbestos exposure has been demonstrated to be the induction of ROS . Oxidative stress occurs when the ROS level in a cell exceeds the antioxidant level. ROS may result in damage to DNA, lipids and proteins and have been implicated in having a role in carcinogenesis . This research has suggested that free radical activity may be involved in the pathogenesis of fiber-induced lung disease.
The ability of RCFs to induce the release of free radicals has been studied in rodent alveolar macrophages. RF1 and RF2 (Japanese ceramic fibers) at 200 g/ml induced a significant production of superoxide anion and a significant increase in intracellular free calcium in guinea pig alveolar macrophages .
Both superoxide anion and increased intracellular calcium are associated with oxidative stress. Superoxide anions may generate hydrogen peroxide and hydroxyl radical, classified as ROS or free radicals. RF2 exposure resulted in a significant depletion of glutathione. Glutathione is a cellular antioxidant that protects cells against oxidative stress; depletion of glutathione is associated with oxidative stress. The RFs did not affect hydrogen peroxide production. In each test, the effects of chrysotile were significantly greater than those of the RFs.
RCF1, MMVF10, and amosite asbestos at 8.24  10 6 f/ml induced a significant depletion of intracellular glutathione in rat alveolar macrophages . RCF1 had similar effects to amosite asbestos, whereas MMVF10 caused the greatest depletion of glutathione.
RCF1, RCF2, and RCF3 induced a greater production of ROMs in human polymorphonuclear cell cultures than RCF4 and chrysotile . A dose-dependent production of ROMs was seen in all RCFs and other MMVFs tested from 25 to 500 g/ml. Quartz had a greater effect on ROM production than all fibers tested.
RCF1 had a high binding capacity for rat immunoglobulin (IgG), a normal component of lung lining fluid . At doses >100 g RCF1, fibers coated with IgG induced a significantly increased superoxide anion release. This supports the premise that lung lining fluid and other substances that fibers are exposed to in vivo may significantly alter the effect of fibers on cells. IgG-coated long fiber amosite asbestos, in spite of a poor binding affinity for IgG, induced a comparable superoxide anion release response to that of coated RCF1. Brown et al.  investigated the ability of RCF1, amosite asbestos, silicon carbide, MMVF10, Cole 100/475 glass fiber, and RCF4 to cause translocation of the transcription factor NF-B to the nucleus in A549 lung epithelial cells. RCF1, amosite asbestos, and silicon carbide produced a significant dose-dependent translocation of NF-B to the nucleus; the other fibers tested did not. Equal fiber numbers were tested.
These cytotoxicity studies indicate that RCFs may share some aspects of their mechanism of action with asbestos. They both affect the production of TNF and ROS as well as cell viability and proliferation. The effects of RCFs have usually been less pronounced than those of asbestos. Results of in vitro studies are difficult to compare, even within studies of different fiber types, because of different study designs, different fiber concentrations and characteristics, and different endpoints.

# C.3 Genotoxic Effects of RCFs
In addition to research assessing the cytotoxicity of RCFs, studies have also assessed the genotoxicity of RCFs. Most genotoxicity assays assess changes in or damage to genetic material. Methods that have been used to investigate the genotoxicity of fibers include cell-free or in vitro cell systems investigating DNA damage, studies of aneuploidy or polyploidy, studies of chromosome damage or mutation, gene mutation assays, and investigations of cell growth regulation . Several studies, described below and in Table C-3, have examined the ability of RCFs to produce genotoxic changes in comparison with asbestos.
Several fibers, including RCF1 and RCF4, were assayed for free radical generating activity using a DNA assay and a salicylate assay . The DNA plasmid assay showed only amosite asbestos to have free radical activity. The salicylate assay showed amosite as well as RCF1 to have free radical activity. Coating the fibers with lung surfactant decreased their hydroxyl radical generation. Differences in RCF1 results in the two assays were proposed to be a result of increased iron release from RCF1 in the salicylate assay. An iron chelator inhibited the RCF hydroxylation of salicylate. RCF4 showed no free radical activity.
When equal fiber numbers were compared, RCF1, RCF2, RCF3, and RCF4 had minimal free-radical-generating activity on plasmid DNA compared with crocidolite and amosite asbestos . RCFs and other MMVF produced a small but insignificant amount of DNA damage. This damage was mediated by hydroxyl radicals. No correlation was found between iron content and free radical generation. At 9.3  10 5 fibers per assay, amosite produced substantial free radical damage to plasmid DNA . Amosite significantly upregulated the transcription factors AP-1 and NFkB; RCF1 had a much smaller effect on AP-1 upregulation only.
SVFs, including ceramic fibers (unspecified), were reported to form hydroxyl radicals based on the formation of the DNA adduct 8-hydroxydeoxyguanosine (8-OH-dG) from 2-de-oxyguanosine (dG) in calf thymus DNA and solution . Ceramic and glasswool fibers had poor hydroxylating capabilities relative to rockwool and slag wool fibers ]. Hydroxyl radical scavengers, such as dimethyl sulfoxide, decreased the hydroxylation. Compounds that increase hydroxyl radical formation, such as hydrogen peroxide, increased hydroxylation. Rockwool in combination with cigarette smoke condensate caused a synergistic increase in 8-OH-dG formation; ceramic and glasswool fibers did not have synergistic effects with cigarette smoke ].
RCF1, RCF2, RCF3, and RCF4 induced nuclear abnormalities, including micronuclei and polynuclei, in Chinese hamster ovary cells . Micronuclei may form when chromosomes or fragments of chromosomes are separated during mitosis. Polynuclei may arise when cytokinesis fails after mitosis. The incidence of micronuclei and polynuclei after exposure to 20 g/cm 2 RCF was from 22% to 33%. At 5 g/cm 2 , chrysotile and crocidolite induced nuclear abnormalities of 49% and 28%, respectively. Amosite, chrysotile, and crocidolite asbestos, and ceramic fibers caused a significant increase in micronuclei in human amniotic fluid cells . The response was dosedependent with asbestos fiber exposure but not with ceramic fiber exposure. Significant increases in chromosomal breakage and hyperdiploid cells were noted after asbestos and ceramic fiber exposure.
RCF1, RCF3, and RCF4 did not induce anaphase aberrations in rat pleural mesothelial cells . Of all fibers tested, UICC chrysotile was the most genotoxic on the basis of weight, number of fibers with a length >4 m and number of fibers corresponding to Stanton=s and Pott=s criteria .
The effect of fibers on the mRNA levels of cfos and c-jun proto-oncogenes and ornithine decarboxylase (ODC) in hamster tracheal epithelial (HTE) cells and rodent pleural mesothelial (RPM) cells were examined . ODC is a rate-limiting enzyme in the synthesis of compounds involved in cell proliferation and tumor promotion, the polyamines.
In HTE cells, crocidolite induced a significant dose-dependent increase in levels of c-jun and ODC mRNA but not c-fos mRNA. RCF1 induced only small nondose-dependent increases in ODC mRNA levels. In RPM cells, crocidolite fibers at 2.5 g/cm 2 significantly elevated levels of c-fos and c-jun mRNA. RCF1 increased proto-oncogene expression at cytotoxic levels of 25 g/cm 2 ; no significant effect was seen at concentrations 5 g/cm 2 .
RCF1 fibers were nonmutagenic in the human-hamster hybrid cell line A L . Chrysotile was a significant inducer of mutations in the same system.
These studies demonstrate that RCFs may share some similar genotoxic mechanisms with asbestos including induction of free radicals, micronuclei, polynuclei, chromosomal breakage, and hyperdiploid cells. Other studies have demonstrated that, using certain methods and doses, RCFs did not induce anaphase aberrations and induced proto-oncogene expression only at cytotoxic concentrations. RCFs were nonmutagenic in human-hamster hybrid cells.

# C.4 Discussion of In Vitro Studies
The toxicity of fibers has been attributable to their dose, dimensions, and durability. Any test system that is designed to assess the potential toxicity of fibers must address these factors. Durability is difficult to assess using in vitro studies because of their acute time course. However, in vitro studies provide an opportunity to study the effects of varying doses and dimensions of fibers in a quicker, more efficient method than animal testing. Although they provide important information about mechanism of action, they do not currently provide data that can be extrapolated to occupational risk assessment.
The association between fiber dimension and toxicity has been documented and reviewed . Fiber length has been correlated with the cytotoxicity of glass fibers . Manville code 100 (JM-100) fiber samples of average lengths of 3, 4, 7, 17, and 33 m were assessed for their effects on LDH activity and rat alveolar macrophage function. The greatest cytotoxicity was reported in the 17 m and 33 m samples, indicating that length is an important factor in the toxicity of this fiber. Multiple macrophages were observed attached along the length of long fibers. Relatively short fibers, <20 m long, were usually phagocytized by one rat alveolar macrophage . Longer fibers were phagocytized by two or more macrophages. Incomplete, or frustrated, phagocytosis may play a role in the increased toxicity of longer fibers. Long fibers (17 m average length) were a more potent inducer of TNF production and transcription factor activation than shorter fibers (7 m average length) . These studies demonstrate the important role of length in fiber toxicity and suggest that the capacity for macrophage phagocytosis may be a critical factor in determining fiber toxicity. The toxicity of individual fibers of the same type of RCFs may differ according to their size in relation to alveolar macrophages.
Several RCF in vitro studies reported a direct association between a longer fiber length and greater cytotoxicity. Hart et al.  reported the shortest fibers to be the least cytotoxic. Brown et al.  reported an association between length and cytotoxic activity but not between diameter and activity. Wright et al.  reported that cytotoxicity was correlated with fibers >8 m length. Yegles et al.  reported that the longest and thickest fibers were the most cytotoxic. The four most cytotoxic fibers had GM lengths 13 m and GM diameters >0.5 m. The production of abnormal anaphases and telophases was associated with Stanton fibers with a length >8 m and diameter 0.25 m. Hart et al.  reported that cytotoxicity increased with fiber length up to 20 m. All of these studies demonstrate the importance of fiber dimensions on cytotoxicity.
Other studies have not reported the length distribution of fiber samples used. When studies are done with RCFs for which specific lengths are assessed for cytotoxicity (such as has been done with glass fibers) , it will be possible to determine the strength of the association between RCF fiber length and toxicity and determine whether a threshold length exists above which toxicity increases steeply.
In addition to providing data on the correlation between fiber length and toxicity, in vitro studies have provided data on the relative toxicity of RCFs compared with asbestos. Uncertainties exist in the interpretation of these studies because of differences in fiber doses, dimensions, and durabilities. RCFs do appear to share some similar mechanisms of action with asbestos. (See references in Tables C-1, C-2, and C-3.) They have similar direct and indirect effects on cells and alter gene function in similar ways. They are capable of inducing enzyme release and cell hemolysis. They may decrease cell viability and inhibit proliferation. They both affect the production of tumor necrosis factor and ROS, and affect cell viability and proliferation. They induce necrosis in rat pleural mesothelial cells. They also may induce free radicals, micronuclei, polynuclei, chromosomal breakage, and hyperdiploid cells in vitro.
In vitro studies also provide an excellent opportunity for investigating the pathogenesis of RCF. However, comparisons are difficult to make between in vitro studies because of differences in fiber doses, dimensions, preparations, and compositions. Important information, such as fiber length distribution, is not always determined.
Even when comparable fibers are studied, the cell line or conditions under which they are tested may vary. Much of the research to date has been done in rodent cell lines and in cells that are not related to the primary target organ. In vitro studies using human pulmonary cell lines should provide pathogenesis data most relevant to human health risk assessment.
Short-term in vitro studies cannot take into account the influence of fiber dissolution and fiber compositional changes that may occur over time. In an in vivo exposure, fibers are continually modified physically, chemically, and structurally by components of the lung environment. This complex set of conditions is difficult to recreate in vitro. Just as it is unlikely that only one factor will be an accurate predictor of fiber toxicity, it is much more unlikely that any one in vitro test will be able to predict fiber toxicity. Best results are obtained by toxicity assessment in several in vitro tests and in comparison with in vivo results. In vitro studies provide an excellent opportunity to investigate factors important to fiber toxicity such as dose, dimension, surface area, and physicochemical composition. They provide the ability to obtain information that is an important supplement to the data of chronic inhalation studies. They do not currently provide information that can be directly applied to human health risk assessment and the development of occupational exposure limits.