1) AMOSITE
2) ANTHOPHYLLITE
3) CROCIDOLITE
4) TREMOLITE

a) In patients with asbestosis, severe pulmonary fibrosis and pulmonary hypertension secondary to increased resistance to pulmonary capillary blood flow can cause compensatory hypertrophy of the right heart (ATSDR, 1990).

a) Chronic constrictive pericarditis has been associated with asbestos exposure (Abejie et al, 2008; Fischbein et al, 1988; Davies et al, 1991).
b) CASE REPORT: Constrictive pericarditis was reported in a 59-year-old boiler operator following a 30-year history of occupational exposure to asbestos-containing material without respiratory protection. His past medical history included an episode of pneumonia and chronic bronchitis. He also had a 20 pack-year history of smoking, although he had quit smoking approximately 23 years prior to the diagnosis of constrictive pericarditis. Chest radiographs showed pleural and pericardial calcifications and cardiac catheterization revealed intermittent equalization of left and right ventricular end diastolic filling pressures, indicative of constrictive pericarditis. Pulmonary function tests also indicated mild obstruction and mildly decreased diffusion capacity (Abejie et al, 2008).

a) An association between pleural plaques and coronary disease has been suggested based on the observation that there has been an abnormal increase in the occurrence of these two diseases together. Further study is still required (Korhola et al, 2001).

a) In a comparison study of previously exposed workers to crocidolite and non-exposed individuals, radiographic findings of parenchymal or pleural disease were associated with the presence of chest pain, in particular anginal pain. More severe pain occurred among former workers, those with heavier exposure and in older subjects, which the authors suggested may be due to a dose-response effect of asbestos exposure. The results were based on a self-administered questionnaire (to assess quality of chest pain; further evaluation not performed) and chest radiography, which were graded independently by two examiners based on International Labor Organization standards (Mukherjee et al, 2000).

a) DEFINITION: Asbestosis is defined as an irreversible diffuse bilateral interstitial fibrosis primarily affecting the lower 2/3 of the lung (ATSDR, 1990; Newhouse, 1983). Either heavy exposure for a short time or lower-level exposure over a longer period may result in asbestosis; cases have resulted from intense exposure of one day's duration (ATSDR, 1990).
b) CLINICAL MANIFESTATIONS: Pleural asbestosis generally develops from chronic, low-level exposure; parenchymal asbestosis is related to higher-level exposures (ATSDR, 1990).
c) DIAGNOSIS: The diagnostic evidence is based on histopathology of the lesions (Craighead, 1982), and it relies on two criteria:
d) CLINICAL COURSE: Pleural thickening progresses at the greatest rate among crocidolite miners and millers who develop early thickening after exposure. This progression decreases with time so that no progression may be noted more than 15 years after onset (de Klerk et al, 1989).

a) DEFINITION: Pleural plaques are focal, irregular thickenings composed of dense bands of avascular collagen occurring predominantly in the submesothelial parietal pleura (Gefter & Conant, 1988).
b) SITES: Plaques may be bilateral and asymmetrical, and are usually located on the parietal pleura of the thorax, diaphragm, mediastinum, or pericardium (Dark & Pingleton, 1983; Mossman & Gee, 1989). Less often, they may occur on the visceral pleura within the interlobar fissure (Gefter & Conant, 1988).
c) CAUSES: Although plaques are the most common chest radiographic manifestation of asbestos exposure, no such exposure can be established for 22% of autopsy-proven cases (Gefter & Conant, 1988). While the overall incidence of plaques increases with dose, there is no linear correlation between plaque severity and total dust exposure (Gefter & Conant, 1988).
d) CLINICAL MANIFESTATIONS: Plaques by themselves are not symptomatic until they become calcified and large enough to restrict chest wall movements and thus affect vital capacity (ATSDR, 1995; (Dark & Pingleton, 1983; Dunn, 1989; Gefter & Conant, 1988; Mossman & Gee, 1989).
e) MALIGNANCY: Pleural plaques are not lung cancer precursors, although persons with pleural plaques have an increased incidence of lung cancer (ATSDR, 1990; Gefter & Conant, 1988; Mossman & Gee, 1989) and possibly malignant mesothelioma (Bianchi et al, 1997).

a) INCIDENCE of BENIGN ASBESTOS PLEURAL EFFUSIONS: The overall incidence of benign asbestos-related pleural effusions was 3.1%, with a 7% incidence in the heavily exposed group and a 0.2% incidence in the indirectly exposed group in one report (Gefter & Conant, 1988). Of all the asbestos-related diseases, it has the shortest latency period, with detection within the first 10 years after exposure (Dunn, 1989; Gefter & Conant, 1988).
b) CLINICAL MANIFESTATIONS: Acutely, fever, chest pain, leukocytosis, and an increased erythrocyte sedimentation rate (ESR) may be seen (Dark & Pingleton, 1983; Dunn, 1989).
c) DIAGNOSIS: Benign asbestos-related pleural effusion is a diagnosis of exclusion. The differential diagnosis includes mesothelioma, metastatic tumor, tuberculosis, and disease involving the superior vena cava, mediastinal nodes, thoracic duct, or pericardium (Gefter & Conant, 1988).
d) CLINICAL COURSE: Although termed "benign," asbestos-related effusions may precede the development of mesothelioma in a small number of patients, necessitating long-term follow-up (Gefter & Conant, 1988). Benign pleural effusions may also lead to functional respiratory impairment because of ensuing fibrosis and pleural thickening (Gefter & Conant, 1988).

a) DEFINITION: Diffuse pleural thickening is a uniform, homogenous, uninterrupted pleural density extending over at least 1/4 of the chest wall with or without accompanying costophrenic angle obliteration (Gefter & Conant, 1988).
b) CAUSES: In a series of 1,373 asbestos-exposed workers, 31.4% of the cases were related to asbestos exposure, 25.4% to confluent plaques, 33% to malignant effusion, trauma, infection, or a combination of these, and 10.3% were presumed extensions of parenchymal fibrosis (McLoud et al, 1985).
c) CLINICAL COURSE: Diffuse pleural thickening may develop as an acute, rapidly progressive process associated with chest pain, or it may assume an indolent, asymptomatic course (Gefter & Conant, 1988). Chronic cases may present with significant pulmonary insufficiency and may require surgical decortication (Gefter & Conant, 1988). Patients presenting with stable pleural plagues are at risk for diffuse pleural thickening and subsequent greater ventilatory impairment (Miller & Miller, 1993).

a) SMOKING: An apparent synergism exists between asbestos-related pulmonary diseases and smoking. The mechanism for this has yet to be established, although several theories have been postulated and tested (Blanc et al, 1988; deShazo et al, 1988; Hobson et al, 1988; Kronenberg, 1989; Mossman & Gee, 1989; Talcott & Antman, 1988) ATSDR, 1995).

a) FERRUGINOUS BODIES have been found in the sputum of asbestos workers (Stewart & Haddow, 1929).

a) Asbestos, as a component of industrial dust, may also produce chronic obstructive airways disease, but further study is required to confirm and understand this relationship (Zejda, 1996).

a) RISK FACTOR: Asbestosis patients with progression of small opacities on chest x-ray over several years are at higher risk of developing lung cancer (Oksa et al, 1998). Although smoking history is also a factor in lung cancer, progression of pulmonary fibrosis may be an independent risk factor.

a) CASE REPORT: Acute renal failure has been reported secondary to retroperitoneal fibrosis which developed in a man with diffuse asbestos-related pleural fibrosis (Maguire et al, 1991).

a) In a case-control study of 43 patients with retroperitoneal fibrosis, the disease was highly associated with occupational asbestos exposure. The age-standardized incidence was 0.10 per 100,000 person-years (Uibu et al, 2003).

a) CASE REPORT: Two men who worked in a shipyard for 40 years were diagnosed with acute myelocytic leukemia (Kishimoto et al, 1988).

a) ASBESTOS CORNS: Warts or areas of thickened skin surrounding implanted asbestos fibers do NOT lead to skin tumors and disappear on removal of the fibers (ILO, 1983).

a) COMPLEMENT ACTIVATION: Asbestos activates complement by an alternative pathway, resulting in leukocyte concentration and lysosomal enzyme release (Dark & Pingleton, 1983).
b) CELLULAR/HUMORAL IMMUNOLOGIC CHANGES: Reports of serum abnormalities have not been consistent (Nash et al, 1981). Despite some variability, most studies indicate that cell-mediated immunity can be depressed (ATSDR, 1995; (Weill & Hughes, 1988). Asbestos, especially chrysotile, can suppress natural killer cell activity and thus interfere with the recognition and destruction of malignant cells (Robinson, 1989).

a) PREDISPOSITION TO INFECTION: Bronchiectasis and unexplained (but commonly encountered) immunologic deficiencies can predispose an asbestotic patient to infections, including tuberculosis (Baris et al, 1988; (Finkel, 1983). Infection can cause further progressive fibrosis, which leads to cor pulmonale.

a) When administered in the drinking water, asbestos had no effect on embryo survival and was not teratogenic in rats (Schneider & Mauere, 1977). It has been reported to affect embryonic development in mice (Valerio, 1980). Chrysotile asbestos was not teratogenic in mice at an oral dose of 143 mcg (Shepards, 2001; (Schardein, 1993).

a) Uncoated chrysotile asbestos fibers were found in lung, liver, and/or placenta digests of 5 stillborn infants, suggesting transplacental transfer of asbestos (Haque et al, 1992).
b) Asbestos is believed to cross the mammalian placental barrier (HSDB , 2001; Lemesch, 1980).
c) Uncoated chrysotile asbestos fibers were found in lung, liver, and/or placenta digests of 5 stillborn infants, indicating transplacental transfer (Haque et al, 1992).
d) Asbestos fibers were found in tissues of stillborn infants at higher frequencies and concentrations than for normal deliveries. Maximum concentrations were seen in lungs, then in liver and placenta. Although placentas from stillbirths averaged 164,500 fibers/g (n = 4), no asbestos fibers were seen in the placentas from normal births. Presence of asbestos fibers was strongly correlated with working status of the mothers (Haque et al, 1996).

a) Listed as: Asbestos
b) Carcinogen Rating: 1

a) TYPES: Primary types of asbestos-related malignancies are bronchial carcinoma and mesothelioma of the pleura and peritoneum (Dunn, 1989; Talcott & Antman, 1988; ATSDR , 2001; Crosignani et al, 1995). There is considerable literature on the relationship between occupational exposure to asbestos and risk for cancer, including mesothelioma (cancer of the lining of the pleural cavity or peritoneum) and lung, laryngeal, ovarian and gastrointestinal cancers (Wu et al, 2015; Swiatkowska et al, 2015; Dunn, 1989; Talcott & Antman, 1988; (IARC, 1987); Sittig, 1991).
b) A positive link between asbestos exposure and mesothelioma has been established both epidemiologically and experimentally.

a) Asbestos fibers in order of toxicity are crocidolite, amosite, and chrysotile.
b) Respirable particles are generally between 0.5 and 5 microns in diameter, with a length-to-width ratio of 3:1. However, in the case of asbestos, some fibers as large as 10 microns in diameter may penetrate to the lower pulmonary regions (ATSDR, 1990).
c) Asbestos fibers were found in lymph nodes of 13 of 21 non-occupationally exposed individuals at appreciably higher levels than in the lung. The authors suggested that lymph nodes may be a better indicator of lifetime exposure to asbestos than lung tissue (Dodson et al, 2000).
d) Following tissue analysis in 20 individuals that died of malignant mesothelioma (17 cases were pleural; 3 were peritoneal), it was found that asbestos fibers could reach the omentum and mesentery. The likelihood of this occurrence could be predicted by the following: heavier inhaled exposures and total amphibole burden tended to favor the migration of amphibole fibers to other extrapulmonary sites. In this study, longer chrysotile fibers were more likely to be present in the extrapulmonary sites (Dodson et al, 2000a).

a) Smoking may impair the lung's ability to clear asbestos fibers and enhance asbestos-induced fibrogenesis (Mossman & Gee, 1989).
b) There has been some controversy as to the quantitative effects between asbestos and tobacco smoke in the occurrence of lung cancer. It was hypothesized that embedded asbestos fibers may provide an area for the deposition of carcinogens from tobacco smoke (Clayton & Clayton, 1993).
c) Although asbestosis and lung cancer are related, the risk for mesothelioma seems to be separate and not related to smoking (ATSDR , 2001; Berry et al, 1985).
d) Rat studies showed that asbestos potentiates physical transport of adherent molecules (including hydrocarbon carcinogens) into the lung where phagocytosis of asbestos fibers incorporates hydrocarbons into pulmonary macrophages (Talcott & Antman, 1988).

a) DOSE-RESPONSE: The chance of developing tumors is dose-related to asbestos exposure, but there is no "critical level" where the risk of cancer is zero (ATSDR, 1990). No known threshold for asbestos induced lung cancer has been established (ATSDR , 2001).
b) Although mesothelial tumors may have a long latency period of up to 68 years, these may occur with an exposure of less than 1 year (ATSDR, 1990; Mowe et al, 1984; Newhouse, 1983).

a) Risk estimates for bronchogenic cancer among workers with asbestosis or significant exposure to asbestos have not been consistently high. This variability can be due to methodological differences.
b) Although persons exposed to asbestos by inhalation have a twofold greater risk of colorectal cancer than unexposed individuals, data were conflicting and insufficient to clearly relate GI tumors or peritoneal mesotheliomas to the direct ingestion of asbestos fibers (Albin et al, 1990; ATSDR, 1990; Edelman, 1988; Weiss, 1990).
c) A 3.4-fold increase in mortality from malignancy (compared to expected rates) has been noted among workers in a factory where the average asbestos level was 80 particles/mL and where crocidolite-containing cigarette filters were manufactured (Talcott et al, 1989).
d) In one study of mesothelioma cases among miners and millers, amphibole (crocidolite and amosite), chrysotile, and tremolite were found in lung fibers and at the highest concentrations among workers with mesothelioma (Dufresne et al, 1995).
e) There is convincing evidence that a relationship exists between pleural malignant mesothelioma and occupational exposure to commercial brands of asbestos. However, many patients with malignant mesothelioma had no previous history of exposure to the fibers. Low-dose asbestos exposure has been related to household and non-occupational (environmental) circumstances. The former consisted of asbestos fibers being brought home by exposed workers in their own clothes, while the latter consisted of exposure that was normally a result of environmental contamination in urban areas near asbestos-producing mines, industries, or factories (living up to 3 miles away from the source may be a risk factor for acquiring asbestosis). Both situations have been responsible for localized outbreaks of pleural mesothelioma, although they are not considered of great relevance in national formal epidemiological studies (Magnani et al, 2000).
f) With respect to occupations involving exposure to asbestos, British construction workers had the highest death rates from peritoneal cancer (PMR=990), and a relatively low rate (PMR=160) for pleural cancer. Other occupations had higher risks of death from pleural tumors and no excess rates of peritoneal cancer. As a rule, the mortality risk for asbestosis followed that of peritoneal, rather than pleural, cancer (Coggon et al, 1995).
g) Very brief exposure to asbestos may be sufficient to increase the risk for cancer. Even a single high-level acute exposure might be enough to increase one's risk. IT IS NOT KNOWN IF THERE IS ANY SAFE ASBESTOS EXPOSURE DOSE ((IARC, 1987)), although one survey suggested a threshold of 25 to 100 fibers/cc years for lung cancer (Browne, 1986).

a) Reports of asbestosis and colorectal cancer showed temporality but not causality of association (Weiss, 1990).

a) Asbestos fibers have been identified within some human specimens of colorectal adenocarcinomas and in extrapulmonary tissues, including the tonsils, thoracic and abdominal lymph nodes, small intestines, pancreas, kidneys, and bone marrow (ATSDR, 1990; Finkel, 1983; Smith et al, 1989). This establishes only site-specific evidence of exposure, not causation (Weiss, 1990).
b) Lung cancer patients had significantly higher levels of ferruginous bodies in lung digests than did controls, even though only one cancer patient had any known exposure to asbestos (Warnock & Churg, 1975). This finding suggests that asbestos may be commonly involved in lung cancer.
c) Animal studies revealed that asbestos fibers can penetrate the GI tract (ATSDR, 1990). Tumorigenesis has also been noted in animal bioassays (Smith et al, 1989).

a) Prolonged exposure to low levels of ozone appears to impair clearance of asbestos from the lungs. In a study of rats exposed to low levels of ozone for 6 weeks and then exposed to aerosolized asbestos fibers for 5 hours, fiber mass and fiber number were significantly greater (P<0.05) than those of a control group of rats exposed only to aerosolized asbestos (Pinkerton et al, 1989).

a) In a Swedish study, mesothelioma was thought to be underreported as an occupational disease (Andersson & Toren, 1995).
b) A significant increase in the number of mesothelioma cases occurred between 1979 and 1993 in the Cappadocian region of Turkey and are considered closely related to environmental exposure to zeolite (a silicate-containing mineral fiber) (Greim, 1997).

a) A large unilateral pleural effusion is the most frequent presenting manifestation of malignant mesothelioma (Gefter & Conant, 1988). Mesothelioma may occasionally present as a solitary pleural mass.
b) A characteristic aching, nonpleuritic chest pain may precede the development of any radiographic findings (Gefter & Conant, 1988; Miller, 1990). In a Japanese study of 106 patients with malignant pleural mesothelioma, chest pain was the most common complaint reported (67 cases) (Kishimoto et al, 2004).
c) A small percentage of patients may present with repeated episodes of benign pleurisy with resolving effusions (Gefter & Conant, 1988).
d) Abdominal pain, a palpable mass, or increased abdominal girth are the usual presenting symptoms of peritoneal mesothelioma (Talcott & Antman, 1988).
e) Pericardial effusion and tamponade, brachial plexopathy, Horner's syndrome, dysphagia, and superior vena cava syndrome are less common presentations (Talcott & Antman, 1988).

a) The 3 remaining patients in this review presented with peritoneal mesothelioma. Two presented with weight loss, abdominal pain, and peritoneal masses on CT. The third patient presented with only ascites. Diagnosis was confirmed by laparotomy in the patients with peritoneal masses and by laparoscopy in the patient with ascites only.
b) The median time from first exposure to symptoms was 35.5 (range, 16 to 53) years. In this study, the overall prognosis was poor and treatment was palliative in most cases; median survival was 6 months(Chan et al, 2003)

a) A meta-analysis of 69 occupational cohorts concluded that asbestos exposure is linked with mesothelioma deaths in a dose-related manner (Goodman et al, 1999).
b) A study of residential proximity to asbestos in California reported that the odds of mesothelioma decreased by approximately 6.3% for every 10 km farther the residents lived from the nearest asbestos source (Pan et al, 2005).

a) Domestic exposure from husbands, fathers, or sons who had direct contact with asbestos was reported in 11 out of 24 women diagnosed with mesothelioma. The epitheloid subtype of mesothelioma was reported in 18 of 24 women followed by biphasic (3 of 24) and sarcomatoid (2 of 24) subtypes (Langhoff et al, 2014).
b) Two genotypes have been identified with increased risk of mesothelioma: GSTM null and NAT2 (slow acetylator). Each confers a 2-fold increased risk, and individuals with both genotypes have a 4-fold higher risk; when combined with asbestos exposure, this risk increases to 7-fold compared to those with "beneficial" genotypes GSTM1 and NAT2 (fast acetylator) (Hirvonen et al, 1995).

a) Non-occupational exposure to asbestos has been associated with diffuse malignant pleural mesothelioma in persons living in areas with high environmental asbestos levels. In this study, the latent time for the development of mesothelioma was longer than with occupational exposure and independent of exposure duration (Metintas et al, 1999).
b) A few cases of mesothelioma have been reported in persons who washed asbestos-contaminated clothes. In one study, 13 of 262 total cases of pleural mesothelioma were thought to be due to such exposure (Dodoli et al, 1992). In another study, five fatal cases of mesothelioma were seen in the wives of asbestos-exposed workers who cleaned their husbands' contaminated clothes and shoes (Schneider et al, 1996).

a) Three cases of mesothelioma were reported in which exposure to asbestos was from drywall joint compound. In 2 of the cases, the men worked directly with drywall products in previous occupations. Patient 1 worked as an assembler and installer of kitchen cabinets for 2 years starting in 1968, when he applied and sanded joint compound as part of the installation of new cabinets. Later, in the 1970s, he worked with joint compound remodeling homes, which included mixing, applying, sanding, and sweeping of joint compound for approximately 5 years at 3 to 5 days/week. He never wore a mask or respirator. Approximately 30 years later, the man developed a benign pleural effusion. The following year, at age 75 years, he was diagnosed with mesothelioma after tissue was obtained from a thorascopic procedure. Special stains were positive for calretinin, CK7, and EMA but negative for CEA, CK20, and TTF1. He died shortly after refusing chemotherapy. Patient 2 was a maintenance worker at various apartment complexes for approximately 20 years from the 1950s until the 1970s, during which time he frequently worked with several drywall products. Not only did he demolish and replace drywall, he performed minor plumbing and electrical repairs. His use of and exposure to joint compound occurred in visibly dusty conditions, in which he sanded, mixed, and swept joint compound. In 1999, the man presented with a recurrent pleural effusion, shortness of breath, right-sided chest pain, and weight loss.In 2001, at age 75 years, he was diagnosed with mesothelioma. The calretinin and keratin 5/6 stains were positive, while the CEA and Leu MJ stains were negative. While the time from first presentation of the pleural effusion to diagnosis was 2 years, he died soon after being diagnosed and declining all therapy. Patient 3 experienced domestic exposure to asbestos from birth through most of his childhood years. His father worked in construction from 1968 to 1974, during which time he frequently used joint compound. Specifically, the father sanded the joint compound, creating a visible dust that settled on his clothes and skin that came home with him. The father also started making home renovations using joint compound when the patient was approximately 6 years old. Approximately 25 years later, he presented with chest pain and shortness of breath. A pleural effusion was revealed by imaging studies and a diagnosis of epithelioid mesothelioma (with a few spindle cells) was made following a biopsy at age 32 years. Stains were positive for calretinin and keratin AE1/AE3 but negative for CEA. The patient was treated with chemotherapy and debulking surgery; however, the tumor was very aggressive and he died. Asbestosis was not observed in these cases; no autopsies were performed. These cases highlight the need to obtain a complete history of exposure to asbestos-containing products, including joint compound used in the 1950s through the 1970s (Dahlgren & Peckham, 2012).

a) A retrospective study of 94 asbestos-related mesotheliomas found amosite asbestos in 81% of the cases. Amosite fibers accounted for 58% of all fibers 5 mcm or greater in length. Tremolite/actinolite/anthophyllite were found in 55% of all cases; chrysotile was found in 21% of all cases; and crocidolite was found in 16% of all cases. This suggests that crocidolite asbestos may not be responsible for most mesotheliomas in the USA (Roggli et al, 1993).
b) A case-referent analysis of asbestos miners from two mining areas in Quebec, Canada, one with high levels of tremolite asbestos and the other with low levels, revealed increased risks of mesothelioma in miners employed at mines producing asbestos with high tremolite concentrations compared to mines with low tremolite concentrations (McDonald et al, 1997).

a) A case-control study conducted in 8 Canadian provinces from 1994 to 1997 showed that occupational exposure to asbestos is associated with an increased risk of lung cancer. In this study, 1681 cases of lung cancer and 2053 controls were identified. Compared with those who were not exposed, workers who were ever exposed to asbestos had a 28% increased risk of lung cancer (odds ratio [OR], 1.28). A 2-fold increase in lung cancer risk occurred in those who had ever been exposed to medium or high levels of asbestos (OR, 2.16) compared with those who were exposed to low concentrations (OR, 1.17) or those unexposed. Duration of exposure to asbestos was found to be unrelated to lung cancer risk. The interaction between smoking and asbestos was multiplicative, with those who had 40 or more pack-years of smoking and were exposed to medium or high asbestos levels having the highest risk of lung cancer, nearly 38-fold higher (OR, 38.59) than those with less than 10 pack-years and no asbestos exposure. The calculated value of the synergy index was 2.1 and the multiplicativity index was 0.99 (Villeneuve et al, 2012).
b) A case-control study of 175 lung cancer patients and 176 controls showed a strong and significant association between asbestos exposure and small cell carcinoma (Relative Risk = 3) and a weaker, but equally significant, association with adenocarcinoma (RR = 2.2) (Kjuus et al, 1986).
c) Although an increased mortality and morbidity from respiratory cancer was noted in a cohort of asbestos cement workers compared to unexposed industrial workers, the overall risk for respiratory cancer (excluding mesothelioma) was not increased compared to the general population (Albin et al, 1990).
d) Deaths from lung cancer in asbestos cement workers were not significantly different after adjustments for age and smoking (standardized mortality ratio decreased from 1.7 to 1.04) (Neuberger & Kundi, 1990).
e) Necropsy studies of 339 amphibole asbestos miners stressed the significant association between asbestosis (and not merely asbestos exposure) and bronchial cancer (Sluis-Cremer & Bezuidenhout, 1989).
f) The risk for lung cancer was higher in persons with radiologic evidence of pulmonary fibrosis, but the risk was also elevated in persons with asbestos exposure and no fibrosis (Wilkinson et al, 1995).
g) A case control study failed to confirm asbestos exposure, but concluded that there was no association between lung cancer and the duration of employment in automotive parts factories (Finkelstein, 1989).
h) Excess risk for cancer of the lung (Relative Risk = 1.8; 95% Confidence Interval = 1.54 to 2.1), pleura (RR = 5.46, 95%; CI = 2.62 to 10.05), and mediastinum (RR = 5; 95% CI = 1.01 to 14.61) were found in a cohort study of 7,996 men and 584 women employed in the Danish asbestos cement industry where fiber levels were more than 0.5 to 2 fiber/mL (Raffn et al, 1989).
i) Danish men employed in the asbestos cement industry have been reported to be at increased risk for lung cancer. In one study, all Danish men with lung cancer from 1943 to 1984 were included, and cancers were stratified according to type. An increase in lung cancer incidence was confirmed, with the highest relative risk being for adenocarcinoma (3.31-fold). Risk was correlated with duration of employment and time since first employment (Raffn et al, 1993).
j) In studies of Finnish cancer patients, lung fiber concentrations of greater than one million per gram of dry tissue were associated with an increased risk for mesothelioma (Tuomi et al, 1991).
k) In a histological study of 414 consecutive cases of lung carcinoma, approximately 60% of the male cases could be attributed to asbestos (Bianchi et al, 1999).
l) Until 1954, most of the world’s chrysotile asbestos production came from 2 mining areas in Quebec, Canada. Non-occupational exposure to chrysotile asbestos and lung cancer risk in women in these two regions compared to 60 control regions was investigated. The number of deaths in women aged 30 or greater between 1970 and 1989 was used to derive age-standardized mortality ratios. An expert panel estimated past asbestos exposure in the asbestos manufacturing regions and the control areas. No excess risk of death from lung cancer from non-occupational asbestos exposure was found. A data analysis compared the observed relative risk of death to the EPA’s asbestos risk assessment model. The EPA model was shown to overestimate the risk of asbestos-induced lung cancer by at least a factor of 10 (Camus et al, 1998).

a) Under the condition of asbestos exposure with a relative risk (RR) of 2 for lung cancer, the estimated RR is 1.6 for laryngeal cancer with an estimated attributable fraction of approximately 37% for asbestos causation in the exposed population. Therefore, asbestos exposure should be considered a cause of laryngeal cancer in humans (Wolff et al, 2015).
b) A matched case-control interview study that corrected for potential confounding by cigarette smoking and alcohol consumption showed a nonsignificant but elevated risk (RR = 1.46) for laryngeal carcinoma among those with occupational asbestos exposure (i.e., boilermakers, sheetmetal workers, pipefitters/plumbers, and carpenters) (Brown et al, 1988).
c) A case control study failed to confirm asbestos exposure but concluded that there was no association between laryngeal cancer and employment duration in automotive parts factories (Finkelstein, 1989).
d) The cross-sectional and longitudinal data derived from personnel in a brake manufacturing plant did not support asbestos as an etiologic factor for laryngeal cancer, but an irritant effect of asbestos was suggested (Parnes, 1990).
e) An excess risk of laryngeal cancer (RR = 5.5) was found among a group of workers first employed in the Danish asbestos cement industry where fiber levels were more than 0.5 to 2 fiber/mL from 1928 to 1940 (Raffn et al, 1989).
f) After correcting for smoking and alcohol consumption, workers heavily exposed to asbestos (with lung cancer RR estimates of 4.06 and 3.28) also had high relative risk estimates for laryngeal cancer (RR = 1.91 and RR = 3.75, respectively) (Smith, 1990).
g) A case-control study was conducted to confirm an association between occupational exposure to asbestos and the risk of developing laryngeal cancer. The study involved 73 cases and 158 controls who reported asbestos exposure, either via job-specific questionnaires or a substance checklist. After adjusting for smoking and alcohol consumption, the odds ratio for laryngeal cancer was 1.2, suggesting there might be a slightly elevated risk of laryngeal cancer in workers with occupational exposure to asbestos, although the results were not statistically significant (Ramroth et al, 2011).

a) A review of published studies on independent cohorts of asbestos workers showed no consistently higher standardized mortality ratios (SMRs) among exposed compared to unexposed populations and no apparent dose-response relationship (Edelman, 1988).
b) A meta-analysis and review of published cohort data stratified cohorts by dose and showed that significant asbestos exposure (as indicated by a lung cancer SMRof at least 200) is associated with an elevated gastrointestinal cancer SMR (Frumkin & Berlin, 1988).
c) A case control study did not confirm asbestos exposure but concluded that there was no association between gastrointestinal cancer and duration of employment in automotive parts factories (Finkelstein, 1989).
d) Excess risk for gastric cancer (relative risk = 1.43) was found in a cohort study of 7996 men and 584 women employed in the Danish asbestos cement industry, where fiber levels were more than 0.5 to 2 fibers/mL (Raffn et al, 1989).
e) No overall excess risk from cancer of the upper and lower gastrointestinal tract was found in a cohort of asbestos cement workers compared to a local reference cohort of unexposed industrial workers (Albin et al, 1990). Another case-control study also failed to find an association between colon cancer and asbestos exposure (Garabrant et al, 1992).
f) Norwegian lighthouse keepers, who consumed cistern drinking water contaminated with asbestos from runoff from asbestos-cement roof tiles for 2 decades, had an excess risk of stomach cancer but not malignant mesothelioma (Andersen et al, 1993).
g) Colorectal cancer occurred with an estimated increase of 1.6% in the incidence density ratio for each fiber-year/mL of asbestos exposure, but no relationship was found between development of colorectal cancer and exposure duration (Albin et al, 1990). A two-fold increase in colon cancer was related to high-level asbestos exposure in one case-control study (Fredriksson et al, 1989).
h) A review of published data from 21 cohorts of asbestos-exposed workers found a 0.97 estimate of the summary standardized mortality or morbidity ratio for colorectal cancer and no dose-response relationship between asbestos exposure and colorectal cancer (Weiss, 1990).
i) Pooled standardized mortality ratio data for stomach cancer among asbestos-exposed men revealed a significantly increased risk of stomach cancer in men exposed to crocidolite or mixed asbestos. Pooled estimates were also significant for mortality. Working in the mining industry appeared to increase the risk of stomach cancer due to asbestos exposure, and a long study follow-up revealed a significantly excess risk of stomach cancer (Peng et al, 2015).
j) Under the condition of asbestos exposure associated with a relative risk (RR) of 2 for lung cancer, the estimated RR for colorectal cancer is 1.1, with the estimated attributable fraction (AF) of 9% for asbestos causation of colorectal cancer in the exposed population, and the estimated RR for stomach cancer is 1.2, with the estimated AF of 17% for asbestos causation of stomach cancer in the exposed population. Thus, the association between asbestos exposure and colorectal cancer is uncertain in humans; the same is true of the association between asbestos exposure and stomach cancer (Wolff et al, 2015).

a) PULMONARY FUNCTION TESTS: After correcting for smoking, age, and other confounders, a restrictive pattern of pulmonary dysfunction with preserved diffusing capacity is expected in patients with asbestosis, unless severity impairs diffusion as well (ATSDR, 1990; Demers et al, 1990; Jones et al, 1988; Kilburn & Warshaw, 1990) 1990a; (Mossman & Gee, 1989; Robins & Green, 1988; Schwartz et al, 1990) 1990a; (Siracusa et al, 1988).

a) LUNG BIOPSY: Open lung biopsy is the only definitive diagnostic test for asbestosis (ATSDR, 1990).
b) SPUTUM STUDIES: Sputum inspection for asbestos fibers or ferruginous bodies lacks sensitivity and specificity (ATSDR, 1990; McDonald et al, 1992). However, sputum cytology remains a useful diagnostic test for neoplasia and lung cancer (ATSDR, 1990). Election microscopy analysis of sputum may be effectively used to assess exposure to asbestos (Harber & Smitherman, 1991).
c) BRONCHOALVEOLAR LAVAGE: Bronchoalveolar lavage (BAL) has been recommended as an adjunct in the diagnosis of asbestos-related pulmonary diseases (Barbers & Abraham, 1989; Delclos et al, 1989; Hayes et al, 1989).
d) OTOLARYNGOLOGIC EXAMINATION: Asbestos workers with hoarseness, pain, or soreness of the throat should be referred for a detailed otolaryngologic examination of the upper respiratory tract looking for the presence of laryngeal cancer (HSDB , 1995).
e) SERUM OSTEOPONTIN: Serum osteopontin levels were used to discriminate between persons with asbestos exposure without early pleural mesothelioma and those with exposure to asbestos with pleural mesothelioma. Serum osteopontin levels were significantly higher for those with pleural mesothelioma, compared with those without pleural mesothelioma (Pass et al, 2005).
f) OSHA REQUIREMENTS: OSHA has specific clinical monitoring requirements for workers exposed to asbestos.

a) In Brazil, experimental work in rodents found positive results in diminishing lung fibrosis induced by paraquat (experimental model for lung fibrosis) when the animals were treated with thalidomide (an anti-mRNA TNF-alpha forming agent) in combination with montelukast (a cysteinyl leukotriene receptor blocker) and acetyl salicylic acid (a prostaglandin-forming inhibitor) (Caldas et al, 1999).

1) Classification: A, human carcinogen.

1) Asbestos, all forms

a) TWA:
b) STEL:
c) Ceiling:
d) Carcinogen Listing: (Ca) NIOSH considers this substance to be a potential occupational carcinogen (See Appendix A in the NIOSH Pocket Guide to Chemical Hazards).
e) Skin Designation: Not Listed
f) Note(s): See Appendix A; See Appendix C

a) A1 :Confirmed Human Carcinogen: The agent is carcinogenic to humans based on the weight of evidence from epidemiologic studies.

a) A : Human Carcinogen.

a) 1 : The agent (mixture) is carcinogenic to humans. The exposure circumstance entails exposures that are carcinogenic to humans. This category is used when there is sufficient evidence of carcinogenicity in humans. Exceptionally, an agent (mixture) may be placed in this category when evidence of carcinogenicity in humans is less than sufficient but there is sufficient evidence of carcinogenicity in experimental animals and strong evidence in exposed humans that the agent (mixture) acts through a relevant mechanism of carcinogenicity.

a) Ca : NIOSH considers this substance to be a potential occupational carcinogen (See Appendix A in the NIOSH Pocket Guide to Chemical Hazards).

a) Category 1 : Substances that cause cancer in man and can be assumed to make a significant contribution to cancer risk. Epidemiological studies provide adequate evidence of a positive correlation between the exposure of humans and the occurence of cancer. Limited epidemiological data can be substantiated by evidence that the substance causes cancer by a mode of action that is relevant to man.

a) K : KNOWN = Known to be a human carcinogen

a) 11 mg/m(3) for 2Y-intermittent -- carcinogenic by RTECS criteria; tumors associated with lung, thorax, or respiratory system

a) 11 mg/m(3) for 1Y-intermittent -- carcinogenic by RTECS criteria; tumors associated with lung, thorax, or respiratory system

a) 1.2 fb/cc for 19Y-continuous -- pulmonary effects

a) 2.8 fb/cc for 5Y -- effects on lung, thorax, or respiration including fibrosis, focal (pneumoconiosis), cough, and dyspnea
b) 400 mppcf for 1Y-continuous -- carcinogenic by RTECS criteria; effects to lung, thorax, or respiration such as fibrosis, focal (pneumoconiosis) and tumors

a) 11 mg/m(3) for 26W-intermittent -- carcinogenic by RTECS criteria; tumors associated with lung, thorax, or respiratory system
b) 8210 ug/m(3) for 6H/20D- intermittent -- fibrosis (interstitial)

a) 13600 ug/m(3) for 6H/5D -intermittent -- fibrosing alveolitis

a) 10 mg/m(3) for 6H/1Y-intermittent -- fibrosis (interstitial); fibrosing alveolitis
b) 7200 ug/m(3) for 6H/20D- intermittent -- fibrosis (interstitial)
c) 11 mg/m(3) for 1Y-intermittent -- carcinogenic by RTECS criteria; tumors associated with lung, thorax, or respiratory system