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Beryllium metal II. a review of the available toxicity data.

Strupp C - Ann Occup Hyg (2010)

Bottom Line: Testing performed under Organisation for Economic Co-Operation and Development guidelines and Good Laboratory Practice concluded that beryllium metal was neither a skin irritant, an eye irritant, a skin sensitizer nor evoked any clinical signs of acute oral toxicity; discrepancies between the current legal classification of beryllium metal in the European Union (EU) and the experimental results were identified.It was concluded that beryllium metal is unlikely to be a classical nonthreshold mutagen.Animal carcinogenicity studies deliver evidence of carcinogenicity in the rat; however, lung overload may be a species-specific confounding factor in the existing studies, and studies in other species do not give convincing evidence of carcinogenicity.

View Article: PubMed Central - PubMed

Affiliation: Harlan Laboratories Ltd, Zelgliweg, Switzerland. chr.strupp@web.de

ABSTRACT
Beryllium metal was classified in Europe collectively with beryllium compounds, e.g. soluble salts. Toxicological equivalence was assumed despite greatly differing physicochemical properties. Following introduction of the Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) regulation, beryllium metal was classified as individual substance and more investigational efforts to appropriately characterize beryllium metal as a specific substance apart from soluble beryllium compounds was required. A literature search on toxicity of beryllium metal was conducted, and the resulting literature compiled together with the results of a recently performed study package into a comprehensive data set. Testing performed under Organisation for Economic Co-Operation and Development guidelines and Good Laboratory Practice concluded that beryllium metal was neither a skin irritant, an eye irritant, a skin sensitizer nor evoked any clinical signs of acute oral toxicity; discrepancies between the current legal classification of beryllium metal in the European Union (EU) and the experimental results were identified. Furthermore, genotoxicity and carcinogenicity were discussed in the context of the literature data and the new experimental data. It was concluded that beryllium metal is unlikely to be a classical nonthreshold mutagen. Effects on DNA repair and morphological cell transformation were observed but need further investigation to evaluate their relevance in vivo. Animal carcinogenicity studies deliver evidence of carcinogenicity in the rat; however, lung overload may be a species-specific confounding factor in the existing studies, and studies in other species do not give convincing evidence of carcinogenicity. Epidemiology has been intensively discussed over the last years and has the problem that the studies base on the same US beryllium production population and do not distinguish between metal and soluble compounds. It is noted that the correlation between beryllium exposure and carcinogenicity, even including the soluble compounds, remains under discussion in the scientific community and active research is continuing.

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Related in: MedlinePlus

UDS in rat primary hepatocytes upon coincubation with 2-acetylaminofluorene and beryllium metal.
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fig2: UDS in rat primary hepatocytes upon coincubation with 2-acetylaminofluorene and beryllium metal.

Mentions: DNA repair synthesis, as an indirect marker of DNA damage, was investigated with beryllium metal extracts in primary rat hepatocytes in an UDS assay. No DNA repair synthesis (and thus no hints of preceding DNA damage) was observed upon beryllium metal exposure (Strupp, 2010). A reduction of the expression of messenger RNA (mRNA) coding for DNA repair proteins was observed upon incubation of a continuous human cell line with a soluble beryllium compound (Joseph et al., 2001) and was suspected to be a relevant mechanism for potential carcinogenicity of beryllium (Beyersmann and Hartwig, 2008). To investigate if this effect on the mRNA level translates into a final functional response of the cells and might be relevant for beryllium metal, the UDS assay was slightly modified. The DNA of rat primary hepatocytes was intentionally damaged by incubation with 2-acetylaminofluorene, a known DNA damaging agent, and coincubated with beryllium metal extracts (Strupp, 2010). DNA repair synthesis was reduced by coincubation with beryllium metal extract. However, it should be noted that this effect was only observed when the concurrent damage of the DNA was massive (>80% cells in repair), while no effects was observed in cells with lower damage to the DNA (Fig. 2).


Beryllium metal II. a review of the available toxicity data.

Strupp C - Ann Occup Hyg (2010)

UDS in rat primary hepatocytes upon coincubation with 2-acetylaminofluorene and beryllium metal.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3020676&req=5

fig2: UDS in rat primary hepatocytes upon coincubation with 2-acetylaminofluorene and beryllium metal.
Mentions: DNA repair synthesis, as an indirect marker of DNA damage, was investigated with beryllium metal extracts in primary rat hepatocytes in an UDS assay. No DNA repair synthesis (and thus no hints of preceding DNA damage) was observed upon beryllium metal exposure (Strupp, 2010). A reduction of the expression of messenger RNA (mRNA) coding for DNA repair proteins was observed upon incubation of a continuous human cell line with a soluble beryllium compound (Joseph et al., 2001) and was suspected to be a relevant mechanism for potential carcinogenicity of beryllium (Beyersmann and Hartwig, 2008). To investigate if this effect on the mRNA level translates into a final functional response of the cells and might be relevant for beryllium metal, the UDS assay was slightly modified. The DNA of rat primary hepatocytes was intentionally damaged by incubation with 2-acetylaminofluorene, a known DNA damaging agent, and coincubated with beryllium metal extracts (Strupp, 2010). DNA repair synthesis was reduced by coincubation with beryllium metal extract. However, it should be noted that this effect was only observed when the concurrent damage of the DNA was massive (>80% cells in repair), while no effects was observed in cells with lower damage to the DNA (Fig. 2).

Bottom Line: Testing performed under Organisation for Economic Co-Operation and Development guidelines and Good Laboratory Practice concluded that beryllium metal was neither a skin irritant, an eye irritant, a skin sensitizer nor evoked any clinical signs of acute oral toxicity; discrepancies between the current legal classification of beryllium metal in the European Union (EU) and the experimental results were identified.It was concluded that beryllium metal is unlikely to be a classical nonthreshold mutagen.Animal carcinogenicity studies deliver evidence of carcinogenicity in the rat; however, lung overload may be a species-specific confounding factor in the existing studies, and studies in other species do not give convincing evidence of carcinogenicity.

View Article: PubMed Central - PubMed

Affiliation: Harlan Laboratories Ltd, Zelgliweg, Switzerland. chr.strupp@web.de

ABSTRACT
Beryllium metal was classified in Europe collectively with beryllium compounds, e.g. soluble salts. Toxicological equivalence was assumed despite greatly differing physicochemical properties. Following introduction of the Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) regulation, beryllium metal was classified as individual substance and more investigational efforts to appropriately characterize beryllium metal as a specific substance apart from soluble beryllium compounds was required. A literature search on toxicity of beryllium metal was conducted, and the resulting literature compiled together with the results of a recently performed study package into a comprehensive data set. Testing performed under Organisation for Economic Co-Operation and Development guidelines and Good Laboratory Practice concluded that beryllium metal was neither a skin irritant, an eye irritant, a skin sensitizer nor evoked any clinical signs of acute oral toxicity; discrepancies between the current legal classification of beryllium metal in the European Union (EU) and the experimental results were identified. Furthermore, genotoxicity and carcinogenicity were discussed in the context of the literature data and the new experimental data. It was concluded that beryllium metal is unlikely to be a classical nonthreshold mutagen. Effects on DNA repair and morphological cell transformation were observed but need further investigation to evaluate their relevance in vivo. Animal carcinogenicity studies deliver evidence of carcinogenicity in the rat; however, lung overload may be a species-specific confounding factor in the existing studies, and studies in other species do not give convincing evidence of carcinogenicity. Epidemiology has been intensively discussed over the last years and has the problem that the studies base on the same US beryllium production population and do not distinguish between metal and soluble compounds. It is noted that the correlation between beryllium exposure and carcinogenicity, even including the soluble compounds, remains under discussion in the scientific community and active research is continuing.

Show MeSH
Related in: MedlinePlus