A Cluster of Beryllium Sensitization Traced to the Presence of Beryllium in Concrete Dust.

BACKGROUND: Chronic beryllium disease (CBD), a granulomatous disease with similarities to sarcoidosis, arises only in individuals exposed to beryllium. Inhaled beryllium can elicit a T-cell-dominated alveolitis leading nonnecrotizing granulomata. CBD can be distinguished from sarcoidosis by demonstrating beryllium sensitization in a lymphocyte proliferation test. RESEARCH QUESTION: Beryllium exposure usually occurs in an occupational setting. Because of the diagnosis of CBD in a patient without evident beryllium exposure, we performed a beryllium-lymphocyte proliferation test (BeLPT) among his work colleagues. STUDY DESIGN AND METHODS: This field study investigated a cohort of work colleagues without obvious beryllium exposure. Twenty-one of 30 individuals were assessed in our outpatient clinic for beryllium sensitization. Therefore, BeLPT was performed with freshly collected peripheral blood mononuclear cells. Data were extracted from clinical charts, including geographical data. Beryllium content in dust samples collected at the workplace was measured by graphite-furnace atomic absorption spectroscopy and was compared with samples from different areas of Germany. RESULTS: For the initial patient, the diagnosis of sarcoidosis was reclassified as CBD based on two positive BeLPT results. Assessment of his workplace did not identify a source of beryllium. However, BeLPTs performed on his workmates demonstrated beryllium sensitization in 5 of 21 individuals, suggesting a local beryllium source. Concrete dust obtained from the building yard, the workplace of the index patient, contained high amounts of beryllium (1138 ± 162 µg/kg), whereas dust from other localities (control samples) showed much lower beryllium content (range, 147 ± 18-452 ± 206 µg/kg). Notably, the control dust collected from different places all over Germany exhibit different beryllium concentrations. INTERPRETATION: We describe a cluster of beryllium-sensitized workers from an industry not related to beryllium caused by environmental exposure to beryllium-containing concrete dust, which exhibited markedly elevated beryllium content. Importantly, analyses of dust samples collected from different localities showed that they contain markedly different amounts of beryllium. Thus, besides workplace-related exposure, environmental factors also are capable of eliciting a beryllium sensitization.

[Management of occupational health for adverse health effects of beryllium and its compounds in workplaces - Recent trends and issues in Japan].

OBJECTIVES: Beryllium is primarily used in its metallic form, in alloys, or in beryllium oxide ceramics. Its physical and mechanical properties make it useful for many applications across a range of industries. Because beryllium is recognized as a sensitizing and carcinogenic agent, the management of occupational health for workers who may be occupationally exposed to beryllium has long been an important issue in the world. Under these circumstances, the U.S. Occupational Safety and Health Administration (OSHA) had published a rule in January 2017, to prevent the development of chronic beryllium disease and lung cancer. This rule strengthens the regulations governing the use of beryllium and its compounds. With the announcement of the OSHA rule in January 2017, the purpose of this study is to gain insight into the health problems and industrial hygiene associated with the use of beryllium and share the issues related to the management of occupational health for persons working with beryllium in Japan. METHODS: We collected information regarding the beryllium industry, beryllium exposure, beryllium-induced health disorders, OSHA rule of January 2017, and regulations for beryllium use in Japan. After reviewing them, we discussed the issues concerning occupational health management of workers exposed to beryllium in Japan. RESULTS: It has been reconfirmed that in recent years, the most serious health problem due to beryllium exposure is chronic beryllium disease caused by beryllium sensitization. Management of occupational health that emphasizes reduction of beryllium sensitization and early detection of beryllium-sensitized workers is important. CONCLUSIONS: It was suggested that the following should be considered as the issues of management of occupational health of workers exposed to beryllium in Japan: (1) Collect epidemiologic data on health hazards from beryllium exposure in Japan. (2) Review the diagnostic items of special medical check-ups. (3) Review the definition of beryllium and its compounds in the Ordinance on Prevention of Hazards due to Specified Chemical Substances.

Chronic Beryllium Disease: Update on a Moving Target.

Beryllium exposure remains an ongoing occupational health concern for workers worldwide. Since the initial Occupational Safety and Health Administration (OSHA) ruling on a permissible exposure limit (PEL) for beryllium in 1971, our understanding of the risks of beryllium sensitization and chronic beryllium disease (CBD) has evolved substantially. A new OSHA ruling released in early 2017 and implemented in late 2018 reduced the PEL for beryllium, increased requirements for medical screening and monitoring, and may ultimately enhance worker protection. This review highlights advances in our understanding of the pathway from beryllium exposure to sensitization and progression to CBD that guided the development of this OSHA ruling. Screening workers exposed to beryllium and management of CBD will also be discussed. Finally, we will discuss the role of beryllium as a cause of morbidity and mortality among exposed workers in this potentially preventable occupational lung disease.

Associations of Metrics of Peak Inhalation Exposure and Skin Exposure Indices With Beryllium Sensitization at a Beryllium Manufacturing Facility.

OBJECTIVES: Peak beryllium inhalation exposures and exposure to the skin may be relevant for developing beryllium sensitization (BeS). The objective of this study was to identify risk factors associated with BeS to inform the prevention of sensitization, and the development of chronic beryllium disease (CBD). METHODS: In a survey of short-term workers employed at a primary beryllium manufacturing facility between the years 1994-1999, 264 participants completed a questionnaire and were tested for BeS. A range of qualitative and quantitative peak inhalation metrics and skin exposure indices were created using: personal full-shift beryllium exposure measurements, 15 min to 24 h process-specific task and area exposure measurements, glove measurements as indicator of skin exposure, process-upset information gleaned from historical reports, and self-reported information on exposure events. Hierarchical clustering was conducted to systematically group participants based on similarity of patterns of 16 exposure variables. The associations of the exposure metrics with BeS and self-reported skin symptoms (in work areas processing beryllium salts as well as in other work areas) were evaluated using correlation analysis, log-binomial and logistic regression models with splines. RESULTS: Metrics of peak inhalation exposure, indices of skin exposure, and using material containing beryllium salts were significantly associated with skin symptoms and BeS; skin symptoms were a strong predictor of BeS. However, in this cohort, we could not tease apart the independent effects of skin exposure from inhalation exposure, as these exposures occurred simultaneously and were highly correlated. Hierarchical clustering identified groups of participants with unique patterns of exposure characteristics resulting in different prevalence of BeS and skin symptoms. A cluster with high skin exposure index and use of material containing beryllium salts had the highest prevalence of BeS and self-reported skin symptoms, followed by a cluster with high inhalation and skin exposure index and a very small fraction of jobs in which beryllium salts were used. A cluster with low inhalation and skin exposure and no workers using beryllium salts had no cases of BeS. CONCLUSION: Multiple pathways and types of exposure were associated with BeS and may be important for informing BeS prevention. Prevention efforts should focus on controlling airborne beryllium exposures with attention to peaks, use of process characteristics (e.g. the likelihood of upset conditions to design interventions) minimize skin exposure to beryllium particles, and in particular, eliminate skin contact with beryllium salts to interrupt potential exposure pathways for BeS risk.

Occupational Exposure to Beryllium. Final rule.

The Occupational Safety and Health Administration (OSHA) is amending its existing standards for occupational exposure to beryllium and beryllium compounds. OSHA has determined that employees exposed to beryllium at the previous permissible exposure limits face a significant risk of material impairment to their health. The evidence in the record for this rulemaking indicates that workers exposed to beryllium are at increased risk of developing chronic beryllium disease and lung cancer. This final rule establishes new permissible exposure limits of 0.2 micrograms of beryllium per cubic meter of air (0.2 [mu]g/m\3\) as an 8-hour time-weighted average and 2.0 [mu]g/m\3\ as a short-term exposure limit determined over a sampling period of 15 minutes. It also includes other provisions to protect employees, such as requirements for exposure assessment, methods for controlling exposure, respiratory protection, personal protective clothing and equipment, housekeeping, medical surveillance, hazard communication, and recordkeeping. OSHA is issuing three separate standards--for general industry, for shipyards, and for construction--in order to tailor requirements to the circumstances found in these sectors.

A novel alternative to environmental monitoring to detect workers at risk for beryllium exposure-related health effects.

The purpose of this study was to describe a methodology for surveillance and monitoring of beryllium exposure using biological monitoring to complement environmental monitoring. Eighty-three Israeli dental technicians (mean age 41.6 ± 1.36 years) and 80 American nuclear machining workers (54.9 ± 1.21 years) were enrolled. Biological monitoring was carried out by analyzing particle size (laser technique) and shape (image analysis) in 131/163 (80.3%) induced sputum samples (Dipa Analyser, Donner Tech, Or Aquiva, Israel). Environmental monitoring was carried out only in the United States (Sioutas impactor, SKC, Inc., Eighty Four, Pa.). Pulmonary function testing performance and induced sputum retrieval were done by conventional methods. Sixty-three Israeli workers and 37 American workers were followed up for at least 2 years. Biological monitoring by induced sputum indicated that a >92% accumulation of <5 µm particles correlated significantly to a positive beryllium lymphocyte proliferation test result (OR 3.8, 95% CI 1.2-11.4, p = 0.015) among all participants. Environmental monitoring showed that beryllium particles were <1 µm, and this small fraction (0.1-1 µ) was significantly more highly accumulated in nuclear machining workers compared to dental technicians. The small fractions positively correlated with induced sputum macrophages (r = 0.21 p = 0.01) and negatively correlated with diffusion lung carbon monoxide single breath (DLCO-SB r = 0.180 p = 0.04) in all subjects. Years of exposure were positively correlated to the number of accumulated particles 2-3 µ in diameter (r = 0.2, p = 0.02) and negatively correlated to forced expiratory volume in one second/forced vital capacity findings (r = -0.18, p = 0.02). DLCO was decreased in both groups after two years of monitoring. Biological monitoring is more informative than environmental monitoring in the surveillance and monitoring of workers in beryllium industries. Induced sputum is a feasible and promising biomonitoring method that should be included in the surveillance of exposed workers.

Biological exposure metrics of beryllium-exposed dental technicians.

Beryllium is commonly used in the dental industry. This study investigates the association between particle size and shape in induced sputum (IS) with beryllium exposure and oxidative stress in 83 dental technicians. Particle size and shape were defined by laser and video, whereas beryllium exposure data came from self-reports and beryllium lymphocyte proliferation test (BeLPT) results. Heme oxygenase-1 (HO1) gene expression in IS was evaluated by quantitative polymerase chain reaction. A high content of particles (92%) in IS >5 µ in size is correlated to a positive BeLPT risk (odds ratio [OR] = 3.4, 95% confidence interval [CI]: 0.9-13). Use of masks, hoods, and type of exposure yielded differences in the transparency of IS particles (gray level) and modulate HO1 levels. These results indicate that parameters of size and shape of particles in IS are sensitive to workplace hygiene, affect the level of oxidative stress, and may be potential markers for monitoring hazardous dust exposures.

Developing effective health and safety training materials for workers in beryllium-using industries.

OBJECTIVE: Despite reduced workplace exposures, beryllium sensitization and chronic beryllium disease still occur. Effective health and safety training is needed. METHODS: Through an Occupational Safety and Health Administration (OSHA) Targeted Topic Training grant and company partners, we developed a training program. Evaluation and validation included knowledge and training reaction assessments and training impact survey. RESULTS: We describe herein the iterative, five-pronged approach: (1) needs assessment; (2) materials development; (3) pilot-testing, evaluation, and material revisions; (4) worker training; and (5) evaluation and validation. Mean posttraining test score increased 14% (82% to 96%; P < 0.005) and were unchanged at 90-day follow-up (94%; P = 0.744). In addition, 49% reported making changes in work practices. CONCLUSIONS: The use of a five-pronged training program was effective and well received and resulted in improved work practices. These materials are available on the OSHA Web site.

Implications of common and special variation for occupational health: examples from beryllium manufacturing.

OBJECTIVE: Common variation is a statistical process-control term for variability associated with usual operating conditions. Special variation occurs when usual operating conditions are disrupted. The objective was to explore the implications for preventive occupational medicine practice of common and special variation in air-level exposure. METHODS: Illustrations are derived from US and UK beryllium facility databases. RESULTS: Special variation may be missed in finite sampling sets, giving a very inaccurate indication of the highest air levels experienced on the job. Depending on the toxicologic model, failure to assess special variation influences the meaningfulness of aspects of occupational prevention, from medical surveillance through risk management. CONCLUSIONS: Jobs and tasks should be characterized for special variation in addition to traditional air sampling. Both special variation and common variation should be considered in occupational medicine preventive practice.

Long-term efficacy of a program to prevent beryllium disease.

BACKGROUND: In 2000, a manufacturer of beryllium materials and products introduced a comprehensive program to prevent beryllium sensitization and chronic beryllium disease (CBD). We assessed the program's efficacy in preventing sensitization 9 years after implementation. METHODS: Current and former workers hired since program implementation completed questionnaires and provided blood samples for the beryllium lymphocyte proliferation test (BeLPT). Using these data, as well as company medical surveillance data, we estimated beryllium sensitization prevalence. RESULTS: Cross-sectional prevalence of sensitization was 0.7% (2/298). Combining survey results with surveillance results, a total of seven were identified as sensitized (2.3%). Early Program workers were more likely to be sensitized than Late Program workers; one of the latter was newly identified. All sensitization was identified while participants were employed. One worker was diagnosed with CBD during employment. CONCLUSIONS: The combination of increased respiratory and dermal protection, enclosure and improved ventilation of high-risk processes, dust migration control, improved housekeeping, and worker and management education showed utility in reducing sensitization in the program's first 9 years. The low rate (0.6%, 1/175) among Late Program workers suggests that continuing refinements have provided additional protection against sensitization compared to the program's early years.

Considerations for the development of health-based surface dust cleanup criteria for beryllium.

The exposure-response patterns with beryllium sensitization (BeS), chronic beryllium disease (CBD) and lung cancer are influenced by a number of biological and physicochemical factors. Recent studies have suggested dermal exposure as a pathway for BeS. In light of the current non-health-based DOE Beryllium Rule surface criteria, the feasibility of deriving a human health-based surface dust cleanup criteria (SDCC) for beryllium was assessed based on toxicology and health risk factors via all potential routes of exposure. Beryllium-specific and general exposure factors were evaluated, including (1) beryllium physicochemical characteristics, bioavailability and influence on disease prevalence, and (2) chemical dissipation, resuspension and transfer. SDCC for non-cancer (SDCC) and cancer (SDCC) endpoints were derived from a combination of modern methods applied for occupational, residential and building reentry surface dust criteria. The most conservative SDCC estimates were derived for dermal exposure (5-379 µg/100 cm for 0.1-1% damaged skin and 17-3337 µg/100 cm for intact skin), whereas the SDCC for inhalation exposure ranged from 51 to 485 µg/100 cm. Considering this analysis, the lowest DOE surface criterion of 0.2 µg/100 cm is conservative for minimizing exposure and potential risks associated with beryllium-contaminated surfaces released for non-beryllium industrial or public sector use. Although methodological challenges exist with sampling and analysis procedures, data variability and interpretation of surface dust information in relation to anthropogenic and natural background concentrations, this evaluation should provide useful guidance with regard to cleanup of manufacturing equipment or remediation of property for transfer to the general public or non-beryllium industrial facilities.

Systematic review: Progression of beryllium sensitization to chronic beryllium disease.

BACKGROUND: The relevance of beryllium sensitization testing for occupational health practice and prevention is unclear. AIMS: To analyse the natural course of beryllium sensitization and clarify the prognosis following cessation of exposure among sensitized workers. METHODS: An electronic literature search was conducted in PubMed, Embase, Toxline and Cochrane databases supplemented by a manual search. Data abstraction and study quality assessment with adapted guideline checklists were performed independently by three reviewers. Seven studies met the eligibility criteria and were included in the systematic review; however, six of the seven studies were of low methodological quality. RESULTS: A substantial (although not specifically quantifiable) proportion of beryllium-sensitized employees will develop chronic beryllium disease (CBD). To date, it is unknown if cessation of exposure in sensitized workers reduces the progression rate to CBD. CONCLUSIONS: To determine the utility of regular assessments for beryllium sensitization among exposed workers, there is a need for prospective studies. This should include detailed and continuous exposure monitoring, regular tests for beryllium sensitization and a thorough diagnostic evaluation of sensitized workers to confirm or exclude CBD.

Efficacy of a program to prevent beryllium sensitization among new employees at a copper-beryllium alloy processing facility.

OBJECTIVES: In 2000, 7% of workers at a copper-beryllium facility were beryllium sensitized. Risk was associated with work near a wire annealing/pickling process. The facility then implemented a preventive program including particle migration control, respiratory and dermal protection, and process enclosure. We assessed the program's efficacy in preventing beryllium sensitization. METHODS: In 2000, the facility began testing new hires (program workers) with beryllium lymphocyte proliferation tests (BeLPTs) at hire and at intervals during employment. We compared sensitization incidence rates (IRs) and prevalence rates for workers hired before the program (legacy workers) with rates for program workers, including program worker subgroups. We also examined trends in BeLPTs from a single laboratory. RESULTS: In all, five of 43 legacy workers (IR = 3.8/1,000 person-months) and three of 82 program workers (IR = 1.9/1,000 person-months) were beryllium sensitized, for an incidence rate ratio (IRR) of 2.0 (95% confidence interval [CI] 0.5, 10.1). Two of 37 pre-enclosure program workers (IR = 2.4/1,000 person-months) and one of 45 post-enclosure program workers (IR = 1.4/1,000 person-months) were beryllium sensitized, for IRRs of 1.6 (95% CI 0.3, 11.9) and 2.8 (95% CI 0.4, 66.2), respectively, compared with legacy workers. Test for trend in prevalence rates was significant. Among 2,159 first-draw BeLPTs during 95 months, we identified seven months when high numbers of redraws were required, with one possible misclassification in this facility. CONCLUSIONS: Fewer workers became sensitized after implementation of the preventive program. However, low statistical power due to the facility's small workforce prevents a definitive conclusion about the program's efficacy. These findings have implications for other copper-beryllium facilities, where program components may merit application.

Progression from beryllium exposure to chronic beryllium disease: an analytic model.

BACKGROUND: Understanding the progression from beryllium exposure (BeE) to chronic beryllium disease (CBD) is essential for optimizing screening and early intervention to prevent CBD. METHODS: We developed an analytic markov model of progression to cbd that assigns annual probabilities for progression through three states: from BeE to beryllium sensitization and then to CBD. We used calculations of the number in each state over time to assess which of several alternative progression models are most consistent with the limited available empirical data on prevalence and incidence. We estimated cost-effectiveness of screening considering both incremental (cost/case) and cumulative program costs. RESULTS: No combination of parameters for a simple model in which risk of progression remains constant over time can meet the empirical constraints of relatively frequent early cases and continuing development of new cases with long latencies. Modeling shows that the risk of progression is initially high and then declines over time. Also, it is likely that there are at least two populations that differ significantly in risk. The cost-effectiveness of repetitive screening declines over time, although new cases will still be found with long latencies. However, screening will be particularly cost-effective when applied to persons with long latencies who have not been previously screened. CONCLUSIONS: To optimize use of resources, the intensity of screening should decrease over time. Estimation of lifetime cumulative CBD risk should consider the declining risk of progression over time.

Beryllium hypersensitivity and chronic beryllium lung disease.

PURPOSE OF REVIEW: This review aims to present the clinician with a synthesis of recent studies that have enhanced our understanding of the epidemiology and pathogenesis of beryllium hypersensitivity (BeH) and chronic beryllium disease (CBD). RECENT FINDINGS: Lower occupational limit levels to beryllium exposure and more stringent preventive measures can decrease the risk for development of BeH and CBD. Beryllium sensitization is determined by a positive beryllium lymphocyte proliferation test (BeLPT). Longitudinal data suggest that BeH progresses to CBD. Together with a comprehensive history the BeLPT may help identify berylliosis in patients erroneously diagnosed to have sarcoidosis. HLA-DPB1-Glu69 marker is associated with increased susceptibility to development of BeH and CBD but poor positive predictive value limits its use; other genetic markers are being investigated. Recent investigations augment our understanding on the role of T-lymphocytes and chemokines in the pathogenesis of beryllium-associated disease. However, the basis for treatment strategies remains scarce. SUMMARY: Our enhanced understanding of beryllium-associated lung disease potentially provides a window to unraveling other granulomatous diseases. However, even more questions beg to be elucidated and additional efforts are needed to translate this body of knowledge into better prevention and treatment.

Use of proliferation tests to evaluate the effects of complexing agents on beryllium toxicity.

Occupational exposure to beryllium may cause chronic beryllium disease (CBD), a granulomatous interstitial pneumonitis caused by a cell-mediated immune response with delayed hypersensitivity initiated by an electrostatic interaction with the MHC class II human leukocyte antigen (HLA). Increased research efforts focus on the development of a CBD treatment by chelation therapy. This work presents an in vitro evaluation of the beneficial effects of beryllium chelation with different organic substrates. We have used a standard beryllium lymphocyte proliferation test (BeLPT) adapted for mouse splenocytes. Three complexing agents, 4,5-dihydroxy-1,3-benzenedisulfonic acid (tiron), nitrilotripropionic acid (NTP) and nitrilotriacetic acid (NTA), were tested using different protocols of the splenocyte proliferation test (SPT). We studied their corrective effect (beryllium pre-exposed splenocytes), their protective effect (ligand pre-exposed splenocytes) and their combined effects at fixed Be:L ratio of 1:2, at fixed Be concentration and at fixed L concentration. We also studied the effect of tiron in preventing splenocyte sensitization to beryllium. All three complexing agents showed a corrective effect and proved efficient in the combined effects, except NTA in the fixed Be:L ratio. Only NTP and tiron showed a significant protection at lower beryllium concentrations, while NTA was not significant. Splenocytes pre-exposed to chelated beryllium did not show sensitization while splenocytes pre-exposed to beryllium were sensitized. We observed a strong correlation between the efficiency of the complexing agent and its affinity towards beryllium. Both tiron and NTP showed a similar affinity towards the beryllium ion that is 10(7) higher than that of NTA.

Consenting to uncertainty: challenges for informed consent to disease screening--a case study.

This paper uses chronic beryllium disease as a case study to explore some of the challenges for decision-making and some of the problems for obtaining meaningful informed consent when the interpretation of screening results is complicated by their probabilistic nature and is clouded by empirical uncertainty. Although avoidance of further beryllium exposure might seem prudent for any individual whose test results suggest heightened disease risk, we will argue that such a clinical precautionary approach is likely to be a mistake. Instead, advice on the interpretation of screening results must focus not on risk per se, but on avoidable risk, and must be carefully tailored to the individual. These points are of importance for individual decision-making, for informed consent, and for occupational health.

Lung/skin connections in occupational lung disease.

PURPOSE OF REVIEW: Exposure to occupational and environmental agents can cause a spectrum of lung diseases that are predominantly immune-mediated. Research and prevention have focused primarily on the respiratory tract. Recent studies, however, suggest that the skin may also be an important route of exposure and site of sensitization. This article highlights key findings, focusing on isocyanate asthma and chronic beryllium disease. RECENT FINDINGS: Occupational lung diseases such as isocyanate asthma and chronic beryllium disease continue to occur despite reduced airborne exposures. Although challenging to quantify, recent studies have documented isocyanate and beryllium skin exposure, even with the use of personal protective clothing. Factors that impair skin barrier function, such as trauma, may promote sensitization to such agents. Animal studies demonstrate that skin exposure to isocyanates and protein allergens is highly effective at inducing sensitization, with subsequent inhalation challenge eliciting asthmatic responses. Limited clinical studies suggest a similar role for human skin exposure to certain sensitizing agents. SUMMARY: Recent findings support a greater focus on the role of skin exposure in the development of certain occupational and environmental lung diseases. Although further research is needed, it is prudent to reduce both skin and inhalation exposures.