Beryllium and lung cancer: A weight of evidence evaluation of the toxicological and epidemiological literature

Abstract

The potential carcinogenicity of beryllium has been a topic of study since the mid-1940s. Since then, numerous scientific and regulatory bodies have assigned beryllium to various categories with respect to its carcinogenicity. Past epidemiologic and animal studies, however, have been marked with notable methodological shortcomings. Because it has been about 16 yr since IARC evaluated beryllium and approximately 50 relevant papers on the topic have been published since that time, we conducted a weight-of-evidence analysis of the historical as well as recent animal and human literature. We also assessed whether recently published studies improved upon methodological shortcomings or shed light upon uncertainties in prior studies. Thirty-three animal studies, principally designed to evaluate the cancer hazard or related mechanisms, and seventeen epidemiologic studies were considered in this assessment. Based on this analysis, the evidence for carcinogenicity of beryllium is not as clear as suggested by previous evaluations, because of the inadequacy of the available smoking history information, the lack of well-characterized historical occupational exposures and shortcomings in the animal studies. We concluded that the increase in potential risk of lung cancer was observed among those exposed to very high levels of beryllium and that beryllium's carcinogenic potential in humans at exposure levels that exist in modern industrial settings should be considered either inadequate or marginally suggestive.

Beryllium Metal II. A Review of the Available Toxicity Data

“…This uncertainty was recently articulated in a review (Hollins et al , 2009) and also in the EU Commission manuscript ‘Information Notices on occupational Diseases: A guide to Diagnosis’ (European Commission, 2009). …”

“…The early epidemiological work had shortcomings in exposure reporting and confounding factors were not adequately addressed (Mancuso and El Attar, 1969; Mancuso et al , 1970, Mancuso, 1979, 1980; Infante et al , 1980; Wagoner et al , 1980; Steenland and Ward, 1991). They were recently reviewed in detail (Hollins et al , 2009). …”

Beryllium in urine by ICP-MS: a comparison of low level exposed workers and unexposed persons

“…Sensitised individuals can go on to develop chronic beryllium disease, a debilitating and potentially fatal lung disease characterised by lesions in the lungs known as granulomas (Brisson 2009;Maier et al 2006). High levels of beryllium exposure are also considered a potential lung cancer risk (Hollins et al 2009). Effects on the lymph nodes, skin and other target organs have also been reported with the majority of these presenting as contact dermatitis and skin lesions (Maier et al 2006;Goyer and Clarkson 2001).…”

Lung Cancer: Mechanisms of Carcinogenesis

“…Much of the human epidemiological data demonstrating increased lung cancer risk are associated with very high exposures which took place before the 1950s in plants involved in the extraction of beryllium hydroxide from beryl ore, ore refi ning, and beryllium processing including the production of beryllium oxide, pure beryllium metal, and beryllium copper alloy and the machining of beryllium-containing materials [ 135 ].…”