Biopersistence of Synthetic Vitreous Fibers and Amosite Asbestos in the Rat Lung Following Inhalation

Hesterberg, Thomas W.; Chase, Gerald R.; Axten, Charles W.; Miller, Warner A.; Musselman, R.P.; Kamstrup, Ole; Hadley, John G.; Morscheidt, C.; Bernstein, David M.; Thévenaz, P.

doi:10.1006/taap.1998.8472

Cited by 165 publications

(58 citation statements)

References 20 publications

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“…These results motivated what were believed at the time to be state-of-the-art nose-only inhalation studies of rats and hamsters exposed to specially prepared, rat-respirable RCF and other SVFs conducted at the Research and Consulting Company (RCC) then located in Geneva. The results of the RCC experiments have been extensively reported (see, e.g., Bunn et al, 1993;Hesterberg et al, 1993Hesterberg et al, , 1995Hesterberg et al, , 1996Hesterberg et al, , 1998McConnell et al, 1994McConnell et al, , 1995McConnell et al, , 1999Mast et al, 1995aMast et al, , 1995bMast et al, , 2000aMast et al, , 2000bHesterberg and Hart, 2001). Exposure to RCF led to fibrosis and tumors in rats and hamsters.…”

Section: Chronic Bioassaysmentioning

confidence: 91%

“…Summary data are presented in various sources (see, e.g., Bernstein et al, 1996Bernstein et al, , 2001aBernstein et al, , 2001bHesterberg et al, 1996Hesterberg et al, , 1998Maxim et al, 2006). Because measured indices of biopersistence vary (among other things) with the exposure method, duration of exposure, and fiber dimensions (particularly length), it is important to compare fiber biopersistence measurements derived from similar protocols, using fibers of similar length, and analyzed using comparable models.…”

Section: Durability/biopersistencementioning

confidence: 99%

“…One common biopersistence index (see EC Directive 97/69/ EEC and ILSI, 2005) is the weighted halftime, T 1/2 , in days of long (≥20 μm) fibers derived from short-term (1-week) inhalation exposures. One series of measurements of various fibers using this index and protocol was published by Hesterberg et al (1998) days) for a series of SVFs and asbestos ranged from a low of 9 days for MMVF 22 (a slagwool) to a high of 817 days for crocidolite asbestos. These are plotted in Figure 3.…”

Section: Durability/biopersistencementioning

confidence: 99%

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Refractory ceramic fiber (RCF) toxicity and epidemiology: A review

Utell

Maxim²

2010

Inhalation Toxicology

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This paper provides a review of the relevant literature on refractory ceramic fibers (RCFs), summarizing relevant data and information on the manufacture, processing, applications, potential occupational exposure, toxicology, epidemiology, risk analysis, and risk management. RCFs are amorphous fibers used for high-temperature insulation applications. RCFs are less durable/biopersistent than amphibole asbestos, but more durable/biopersistent than many other synthetic vitreous fibers (SVFs). Moreover, as produced/used, some RCFs are respirable. Toxicology studies with rodents using various exposure methods have shown that RCFs can cause fibrosis, lung cancer, and mesothelioma. Interpretation of these animal studies is difficult for various reasons (e.g., overload in chronic inhalation bioassays). Epidemiological studies of occupationally exposed cohorts in Europe and the United States have demonstrated measurable effects (e.g., mild respiratory symptoms and pleural plaques) but no disease (i.e., no interstitial fibrosis, no excess lung cancer, and no mesothelioma) to date. The RCF industry, working cooperatively with various government agencies in the United States, has developed a comprehensive product stewardship program (PSP) to identify and control risks associated with occupational exposure. One provision of the PSP is the adoption of a voluntary recommended exposure guideline (REG) of 0.5 fibers/milliliter (f/ml). Selected on the basis of prudence and demonstrated feasibility, compliance with the REG should reduce risks to levels between 0.073/1000 and 1.2/1000, based on extrapolations from chronic animal inhalation studies.

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Section: Chronic Bioassaysmentioning

confidence: 91%

Section: Durability/biopersistencementioning

confidence: 99%

Section: Durability/biopersistencementioning

confidence: 99%

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Refractory ceramic fiber (RCF) toxicity and epidemiology: A review

Utell

Maxim²

2010

Inhalation Toxicology

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“…The ability of the fiber to remain in the lung, termed durability if measured in in vitro studies, or biopersistence if measured in in vivo studies has also been found to be a key determinant of fiber toxicity (ATSDR, 2004; Bernstein et al., 2001a,b; Eastes & Hadley, 1994; Eastes et al., 1996; Hesterberg et al., 1994, 1998; ILSI Working Group, 2005; McConnell, 2000; Maxim et al., 2006; Moolgavkar et al., 2000, 2001a,b,c; Oberdörster, 2000).

Dissolution rates are measured in in vitro studies in simulated lung fluid.

…”

Section: Other Relevant Fiber Propertiesmentioning

confidence: 99%

“…results reported in Bernstein et al., 1996, 2001a,b; Hesterberg et al., 1996, 1998; HVGB, 1998; Kudo & Aizawa, 2008; Musselman et al., 1994). Measured WT 1/2 values vary among the studies, with an arithmetic mean value of approximately 59 days.…”

Section: Biopersistencementioning

confidence: 99%

Perspectives on refractory ceramic fiber (RCF) carcinogenicity: comparisons with other fibers

Greim

Utell

Maxim³

et al. 2014

Inhalation Toxicology

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In 2011, SCOEL classified RCF as a secondary genotoxic carcinogen and supported a practical threshold. Inflammation was considered the predominant manifestation of RCF toxicity. Intrapleural and intraperitoneal implantation induced mesotheliomas and sarcomas in laboratory animals. Chronic nose-only inhalation bioassays indicated that RCF exposure in rats increased the incidence of lung cancer and similar exposures resulted in mesothelioma in hamsters, but these studies may have been compromised by overload. Epidemiological studies in the US and Europe showed an association between exposure and prevalence of respiratory symptoms and pleural plaques, but no interstitial fibrosis, mesotheliomas, or increased numbers of lung tumors were observed. As the latency of asbestos induced mesotheliomas can be up to 50 years, the relationship between RCF exposure and respiratory malignances has not been fully determined. Nonetheless, it is possible to offer useful perspectives. RCF and rock wool have similar airborne fiber dimensions and biopersistence. Therefore, it is likely that these fibers have similar toxicology. Traditional rock wool has been the subject of numerous cohort and case control studies. For rock wool, IARC (2002) concluded that the epidemiological studies did not provide evidence of carcinogenicity. Based on analogies with rock wool (read across), it is reasonable to believe that increases in lung cancer or any mesotheliomas are unlikely to be found in the RCF-exposed cohort. RCF producers have developed a product stewardship program to measure and control fiber concentrations and to further understand the health status of their workers.

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Asbestos, chromosomal deletions, and tumor suppressor gene alterations in human malignant mesothelioma

1999

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Exposure to the carcinogen asbestos is considered to be a major factor contributing to the development of most malignant mesotheliomas (MMs). We highlight the role of asbestos in MM and summarize cytogenetic and molecular genetic findings in this malignancy. The accumulation of numerous clonal chromosomal deletions in most MMs suggests a multistep process of tumorigenesis, characterized by the loss and/or inactivation of multiple tumor suppressor genes (TSGs). Cytogenetic and loss of heterozygosity (LOH) analyses of MMs have demonstrated frequent deletions of specific sites within chromosome arms 1p, 3p, 6q, 9p, 13q, 15q, and 22q. Furthermore, TSGs within two of these regions, i.e., p16/CDKN2A-p14ARF at 9p21 and NF2 at 22q12, are frequently altered in MMs. Homozygous deletion appears to be the major mechanism affecting p16/CDKN2A-p14ARF, whereas inactivating mutations coupled with allelic loss occur at the NF2 locus. Finally, recent studies have demonstrated the presence and expression of simian virus 40 (SV40) in many MMs. SV40 large T antigen has been shown to inactivate the TSG products Rb and p53, suggesting the possibility that asbestos and SV40 could act as cocarcinogens in MM. The frequent occurrence of homozygous deletions of p16/CDKN2A-p14ARF and the ability of SV40 Tag to bind TSG products suggest that perturbations of both Rb- and p53-dependent growth-regulatory pathways are critically involved in the pathogenesis of MM.

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Biopersistence of Synthetic Vitreous Fibers and Amosite Asbestos in the Rat Lung Following Inhalation

Cited by 165 publications

References 20 publications

Refractory ceramic fiber (RCF) toxicity and epidemiology: A review

Refractory ceramic fiber (RCF) toxicity and epidemiology: A review

Perspectives on refractory ceramic fiber (RCF) carcinogenicity: comparisons with other fibers

Asbestos, chromosomal deletions, and tumor suppressor gene alterations in human malignant mesothelioma

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