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5 Genotoxicity and Carcinogenicity
Pages 106-122

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From page 106... ... Beryllium chloride, beryllium nitrate, beryllium sulfate, and beryllium oxide have been shown to be nongenotoxic in the Ames plate incorporation assay and assays with Escherichia coli pol A, E coli WP-2 uvr A, and Saccharomyces cerevisiae (Table 5-1) Read the entire page →
From page 107... ... 1991 Eschericia coli WP-2 uvrA BeSO4 Negative Negative Dunkel et al. 1984 Rec assay Bacillus subtilis BeSO4 -- Positive Kada et al. Read the entire page →
From page 108... ... 1981 Human lymphocytes BeSO4 -- Negative Andersen 1983 Mouse macrophage P388D1 BeSO4 -- Negative Andersen 1983 cells DNA repair Rat hepatocytes BeSO4 -- Negative Williams et al. 1982, 1989 Transformation assay Syrian hamster embryo cells BeSO4 -- Positive DiPaolo and Casto 1979 Rat respiratory epithelial Rocket-exhaust -- Mixed Steele et al. Read the entire page →
From page 109... ... 2, beryllium nitrate; BeO, beryllium oxide; BeSO4, beryllium sulfate. Source: Adapted from ATSDR 2002. Read the entire page →
From page 110... ... . Positive genotoxic results have been reported with beryllium sulfate in the Bacillus subtilis rec assay (Kada et al. Read the entire page →
From page 111... ... It pointed out that the risk of lung cancer was consistently higher in plants in which there was excess mortality from nonmalignant respiratory disease. IARC also concluded that the association between lung-cancer risk and beryllium exposure did not appear to be confounded by smoking. Read the entire page →
From page 112... ... (2002) have reported that alternative adjustments and comparisons to address those issues left no statistical association between beryllium exposure in the workers and lung cancer. Read the entire page →
From page 113... ... The Schubauer-Berigan et al. reanalysis confirmed a significant association between beryllium exposure and lung-cancer risk, although the exposure metric and time lag that revealed the strongest evidence differed from those in the original study. Read the entire page →
From page 114... ... The mean particle size of the beryllium sulfate aerosol was 0.118 µm. Exposure lasted up to 72 weeks. Read the entire page →
From page 115... ... ; particle size, 1.4 µm (GSD, 1.9 µm) Short-term and subchronic exposure Vorwald and Reeves Rat Intratracheal 4.5 mg of Be as BeO, 0.1071 mg of Be as Lung tumors began to appear after 8 months; 1959 BeSO4 (three injections over 3 weeks) Read the entire page →
From page 116... ... ; particle size, developed lung tumors after 3 and 18 months, 0.21 µm (mean) respectively; at 3 months, older rats had fewer lung neoplasms than younger rats Wagner et al. Read the entire page →
From page 117... ... 1991 Rat hepatic In vitro 50 µM BeSO4 BeSO4 inhibited cell division during G1 phase of BL9L cells cell cycle, but expression of c-myc was maintained in serum-stimulated cells Nickell-Brady Rat Inhalation Be at 410, 500, 830, 980 mg/m3 (single Analysis of p53 and c-raf-1 genes in neoplasms et al. 1994 exposure; lung burdens, 40, 110, 360, 430 did not indicate genetic alterations; weak µg) Read the entire page →
From page 118... ... 2002 Mouse In vitro 1-5 nM BeF2 Phosphorylation increased kinases MEK1, peritoneal ERK1, p38 MAPK, JNK; increases also seen in macrophages NF-κB, CREB transcription factors, c-fos, c-myc Abbreviations: Al, aluminum; Be, beryllium; BeCl2, beryllium chloride; BeF2, beryllium fluoride; BeO, beryllium oxide; BeSO4, beryllium sulfate; Co, cobalt; Cr, chromium; Cu, copper; GSD, geometric standard deviation; Ni, nickel. Read the entire page →
From page 119... ... Malignant lung neoplasms developed in a dose-related manner after exposure to either beryllium oxide or beryllium chloride but were not found in the controls. The carcinogenicity of two beryllium ores, bertrandite and beryl, was evaluated in male squirrel monkeys (Saimiri sciurea) Read the entire page →
From page 120... ... classifies beryllium as a likely human carcinogen on the basis of epidemiologic studies that found increases in lung cancer and supporting evidence from animal studies that beryllium induces lung cancer in rats and monkeys. For carcinogens, EPA calculates an inhalation unit risk, which is the upper-bound excess lifetime cancer risk estimated to result from continuous exposure to an agent at a concentration of 1 µg/m3. Read the entire page →
From page 121... ... CONCLUSIONS AND RECOMMENDATIONS There is evidence from controlled studies that exposure to beryllium can cause lung cancer in both sexes of rats, and one study reported lung tumors in monkeys. Epidemiologic studies have reported increases in lung-cancer risk in two worker cohorts exposed to beryllium. Read the entire page →
From page 122... ... • Is cancer risk driven by peak exposures, by cumulative exposures, or by other dose metrics? • How have earlier and later exposures of beryllium workers to other lung carcinogens affected disease incidence? Read the entire page →

From page 106...

... Beryllium chloride, beryllium nitrate, beryllium sulfate, and beryllium oxide have been shown to be nongenotoxic in the Ames plate incorporation assay and assays with Escherichia coli pol A, E coli WP-2 uvr A, and Saccharomyces cerevisiae (Table 5-1)

5 Genotoxicity and Carcinogenicity Pages 106-122

5 Genotoxicity and Carcinogenicity
Pages 106-122