Toxicokinetic and toxicodynamic studies of beryllium

Stiefel, Th.; Schulze, K.; Zorn, H.; Tölg, G.

doi:10.1007/bf01270905

Cited by 48 publications

(18 citation statements)

References 16 publications

(12 reference statements)

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“…This concentration is lower than the values of 280-1000 pg ml −1 established for humans (Paschal et al, 1998;Stiefel et al, 1980) or 1580 and 830 pg ml −1 as respectively established by Horng et al (2002) for steel production workers and for controls. In comparison with the controls, all exposed groups have, as expected, signifi cantly higher Be concentration in urine as well as for blood and all tissues analysed in this study (lung, spleen, liver and kidney).…”

Section: −1mentioning

confidence: 56%

“…Levels ranging from 0.28 to 1 μg L −1 were established by Paschal et al (1998) and Stiefel et al (1980) while other studies reported mean urinary Be concentrations ranging from <0.03 to 0.4 μg L −1 (Apostoli and Schaller, 2001). Stiefel et al (1980) found increased levels in the urine of smokers (2 μg L −1 compared with 0.9 μg L −1 for non smokers). However, it seems obvious that suffi cient data are not currently available to be able to propose a biological exposure index (BEI) for urinary Be.…”

Section: Introductionmentioning

confidence: 92%

“…In rats and dogs, wholebody clearance of inhaled Be follows a single-phase exponential curve with a half-life of 300-400 days (Finch et al, 1990;Rhoads and Sanders, 1985). Absorbed Be is generally eliminated primarily in the urine (Stiefel et al, 1980), whereas excretion of unabsorbed Be is primarily via the fecal route shortly after mucociliary clearance from the respiratory tract (Finch et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

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Urinary levels, tissue concentrations and lung inflammation after nose‐only exposure to three different chemical forms of beryllium

Müller¹,

Mazer²,

Salehi³

et al. 2010

J of Applied Toxicology

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This study aimed to determine the toxicity and toxicokinetic of three Be chemical species A total of 120 mice (four groups of 30) were nose-only exposed. The first group was used as a control while the three others were exposed to 250 microg m(-3) of fine particles of three different Be species (Be metal, Be-F; Be oxide, BeO-F; Be aluminium, BeAl-F). Exposure lasted over three consecutive weeks, five days per week and 6 h per day. Blood and several tissues were collected one week after exposure. Urines were collected before the beginning of exposure, at the end of every week of exposure and one week after exposure. Results showed that urine concentrations were different from one Be species to another and that excretion continued after the end of exposure. Except for BeO-F, where Be urine concentrations were stable during the three weeks of exposure, concentrations of Be-F and BeAl-F reached a peak after the first week. According to particle size, BeO-F obtained the highest theoretical pulmonary deposition rate, which partially led to the highest Be lung concentration. This group also presented the lowest urine concentration but that did not lead to more severe lung inflammation. Moreover, even if BeAl-F obtained the lowest percentage theoretical pulmonary deposition, it showed the highest Be urinary concentration, the lowest Be lung concentration and the lowest lung toxicity. In this specific case, a high Be concentration in urine did not reflect a high exposure or a severe toxic effect.

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Section: −1mentioning

confidence: 56%

Section: Introductionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

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Urinary levels, tissue concentrations and lung inflammation after nose‐only exposure to three different chemical forms of beryllium

Müller¹,

Mazer²,

Salehi³

et al. 2010

J of Applied Toxicology

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“…CBD has been observed after beryllium exposure in compliance with the air standard of 2 µg/m 3 [63][64][65][66]. Characteristic symptoms of CBD are dyspnoea on exertion, weight loss, nonproductive cough, fatigue, chest pain, anorexia, and weakness [67][68][69].…”

Section: R Klein Et Almentioning

confidence: 99%

Diagnostic relevance of the lymphocyte transformation test for sensitization to beryllium and other metals (IUPAC Technical Report)

Klein¹,

Schwenk²,

Heinrich‐Ramm³

et al. 2004

Pure and Applied Chemistry

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The lymphocyte transformation test (LTT) has been proven useful especially in the diagnosis of drug-induced allergic disorders. It is an in vitro test which is based on the fact that lymphocytes, which have been sensitized by a certain antigen, transform into blasts and proliferate when they are again exposed to this antigen. This proliferation is determined by measurement of the incorporation of [3H ]-thymidine or bromodeoxyuridine into replicating DNA. The test has the advantage over skin tests of avoiding re-exposure of individuals, and it was, therefore, hoped that it may also help to diagnose metal allergies and especially sensitization toward beryllium. However, the LTT measures only the sensitization of lymphocytes, but not the effector reaction, i.e., there may be positive results in exposed individuals even in the absence of clinical symptoms. There are several reports evaluating the LTT toward gold salts (Au), amalgam (Hg), nickel (Ni), beryllium (Be), and several other metals. With metals other than Be, the LTT appears to be of little use. In contrast, the LTT with Be may, indeed, define patients at risk of developing chronic beryllium disease (CBD), which affects mainly the respiratory tract and may even cause death. Beryllium sensitization progresses to CBD at a rate of 7-11 % per year. Since the Be-LTT can detect sensitization in workers who have not yet developed a disease it is an important diagnostic tool to detect individuals at risk. In conclusion, the LTT can detect a cell-mediated immunological response of an individual to metals. However, for most metals its usefulness is questionable, with the exception of Be; a positive Be-LTT can identify not only patients with CBD, but also persons at risk of developing CBD in later years.

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“…Beryllium can be measured in blood and urine, but it is not known to what extent the concentration of beryllium in these fluids relates to recent or past exposure. Observations on newly exposed workers suggest that beryllium in urine may be a reflection of the current exposure (27), but it has also been reported that the urinary excretion of beryllium may remain elevated several years after the end of exposure (28,29). In persons nonoccupationally exposed, the mean concentration of beryllium in urine and blood is around 1 ,ug/L (27).…”

Section: Berylliummentioning

confidence: 99%

Biomonitoring Exposure to Metal Compounds with Carcinogenic Properties

Léonard¹,

Bernard²

1993

Environmental Health Perspectives

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Several metals such as arsenic, beryllium, chromium and nickel are carcinogenic to man when they occur in certain well-defined physicochemical forms. The carcinogenic potential of these metals is linked to their mutagenic properties. The determination ofthe metal or possibly of its metabolites in biological media and the cytogenetic examination of somatic cells are two methods that can currently be used to monitor exposure of populations at risk. Due to the use of inappropriate methodology, the value of the positive cytogenetic results published so far appears questionable. By contrast, the concentrations of metals in blood, urine, or other biological materials can be determined with accurate and precise methods. Although it does not permit a direct assessment of the carcinogenic risk, this approach is currently the most suitable for monitoring exposed populations. Carcinogenicity and Mutagenicity of Metal SaltsThere is clear evidence that arsenic, beryllium, chromium, and nickel, when present in certain well defined physicochemical forms, represent a carcinogenic hazard to man. Earlier observations of cadmium carcinogenicity were not sustained by the recent updates of cohorts. To varying degrees, the epidemiological findings have been duplicated by positive results in laboratory animals but, if we except the case of arsenic, metal carcinogenesis is not a problem of environmental contamination at trace levels but is relevant to occupational medicine (1).From the results of the several hundreds short-term tests performed to assess the carcinogenic properties of metal salts on the basis of mutagenicity (2) significant reversion in the Ames test, although they produce forward mutations in mammalian somatic cells or in some bacteria, i.e., resistance to antibiotics or other detectable mutations that can be positively selected.As far as mechanisms are concerned, forward mutations may be caused by unrepaired or unrepairable insertions, deletions, rearrangements, or point mutations that are not detectable in the Ames test. In that respect, it is of interest to point out that the fluctuation assay is a more sensitive technique than the plate incorporation assay. This illustrates the importance of choosing a method appropriate for highly toxic substances. These assays have also demonstrated that the response obtained depends on the ability of the metal to penetrate the cell and to interact with DNA, the chemical speciation, the physical properties [oxidation state, e.g., Cr(VI) and Cr(III), As(V), and As(III); charge, solubility, crystal form, properties of ligands, complex stereochemistry] and the possible interactions with other xenobiotics are, in that respect, critical. Metals such as Ni(II) or Cd(II) may be precipitated as insoluble phosphate salts due to orthophosphate ions present in the normal bacteriological culture medium and, for this reason, may not be detected as mutagenic. Some of the variation observed in the results of the bioassays of different metal salts could, therefore, be due to differences in bioav...

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Toxicokinetic and toxicodynamic studies of beryllium

Cited by 48 publications

References 16 publications

Urinary levels, tissue concentrations and lung inflammation after nose‐only exposure to three different chemical forms of beryllium

Urinary levels, tissue concentrations and lung inflammation after nose‐only exposure to three different chemical forms of beryllium

Diagnostic relevance of the lymphocyte transformation test for sensitization to beryllium and other metals (IUPAC Technical Report)

Biomonitoring Exposure to Metal Compounds with Carcinogenic Properties

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