Immunotoxicity of 3 chemical forms of beryllium following inhalation exposure.

The toxicity of 3 chemical forms of beryllium (Be) was compared in this study. A total of 160 mice equally divided into 4 groups were exposed by inhalation (nose only) for 3 consecutive weeks, 5 d/week, 6 h/d. One group was used as control, while the 3 others were exposed to fine particles of Be metal, Be oxide (BeO), or Be aluminum (BeAl). Except for the controls, the target level of exposure was 250 µg/m(3). In all, 35 mice/group were sacrificed 1 week postexposure and another 5 mice 3 weeks postexposure. The BeO group showed the highest lung Be concentration with higher interleukin 12 (IL-12) and interferon-γ (IFN-γ) levels, while the Be group produced the most severe lung inflammation and higher tumor necrosis factor-α (TNF-α) and CD4+ T cells levels. Data suggested that Be and BeO apparently produced more pulmonary toxicity than BeAl. However, this conclusion is not definitive, because of different confounding factors such as particle sizes, specific surface area, and solubility.

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

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.

Beryllium contamination and exposure monitoring in an inhalation laboratory setting.

Beryllium (Be) is used in several forms: pure metal, beryllium oxide, and as an alloy with copper, aluminum, or nickel. Beryllium oxide, beryllium metal, and beryllium alloys are the main forms present in the workplace, with inhalation being the primary route of exposure. Cases of workers with sensitization or chronic beryllium disease challenge the scientific community for a better understanding of Be toxicity. Therefore, a toxicological inhalation study using a murine model was performed in our laboratory in order to identify the toxic effects related to different particle sizes and chemical forms of Be. This article attempts to provide information regarding the relative effectiveness of the environmental monitoring and exposure protection program that was enacted to protect staff (students and researchers) in this controlled animal beryllium inhalation exposure experiment. This includes specific attention to particle migration control through intensive housekeeping and systematic airborne and surface monitoring. Results show that the protective measures applied during this research have been effective. The highest airborne Be concentration in the laboratory was less than one-tenth of the Quebec OEL (occupational exposure limit) of 0.15 microg/m(3). Considering the protection factor of 10(3) of the powered air-purifying respirator used in this research, the average exposure level would be 0.03 x 10(- 4) microg/m(3), which is extremely low. Moreover, with the exception of one value, all average Be concentrations on surfaces were below the Quebec Standard guideline level of 3 microg/100 cm(2) for Be contamination. Finally, all beryllium lymphocyte proliferation tests for the staff were not higher than controls.

Immunological responses in C3H/HeJ mice following nose-only inhalation exposure to different sizes of beryllium metal particles.

Beryllium is used in a wide variety of industries. Chronic beryllium disease is the most common occupational disease among workers following exposure to Be. The objective of this study was to determine the immunologic effects of two different particle sizes of Be metal, <2.5 microm (fine Be or Be-F) and <10 microm (inhalable Be or Be-I) on C3H/HeJ mice following 3 weeks of nose-only inhalation exposure at a target concentration of 250 microg m(-3). Mice were sacrificed either on day 28 or day 42 (Be-F group only) after exposure. The mass median aerodynamic diameter obtained in the inhalation chamber was 1.5 +/- 0.1 microm for Be-F and 4.1 +/- 0.6 microm for Be-I. Results showed peri-bronchial inflammation with early granulomatous changes in exposed mice. The extent of the inflammation appeared more severe for mice sacrificed at day 42. Splenocyte proliferation was higher for mice exposed to fine particles compared with Be-I and control animals. Flow-cytometric analysis indicated a significantly greater expression of CD4(+), CD8(+) and intracellular IFN-gamma expression for both Be particle sizes, particularly for fine particles. Cytokine assays of bronchoalveolar lavage revealed significantly greater levels of IL-12, TNF-alpha and IFN-gamma for mice exposed to fine particles. Our findings suggest that exposure to fine particles may induce more pronounced immunological effects than inhalable particles.