(1984). Polychlorinated Biphenyls (PCBs) and Polybrominated Biphenyls (PBBs): Biochemistry, Toxicology, and Mechanism of Action. CRC Critical Reviews in Toxicology: Vol. 13, No. 4, pp. 319-395.

Polychlorinated biphenyls (PCBs) and polybrominated biphenyls (PBBs): biochemistry, toxicology, and mechanism of action

A review on human exposure to brominated flame retardants—particularly polybrominated diphenyl ethers

The type of lung disease caused by metal compounds depends on the nature of the offending agent, its physicochemical form, the dose, exposure conditions and host factors. The fumes or gaseous forms of several metals, e.g. cadmium (Cd), manganese (Mn), mercury (Hg), nickel carbonyl (Nl(CO)4, zinc chloride (ZnCl2), vanadium pentoxide (V2O5), may lead to acute chemical pneumonitis and pulmonary oedema or to acute tracheobronchitis. Metal fume fever, which may follow the inhalation of metal fumes e.g. zinc (Zn), copper (Cu) and many others, is a poorly understood influenza-like reaction, accompanied by an acute self-limiting neutrophil alveolitis. Chronic obstructive lung disease may result from occupational exposure to mineral dusts, including probably some metallic dusts, or from jobs involving the working of metal compounds, such as welding. Exposure to cadmium may lead to emphysema. Bronchial asthma may be caused by complex platinum salts, nickel, chromium or cobalt, presumably on the basis of allergic sensitization. The cause of asthma in aluminium workers is unknown. It is remarkable that asthma induced by nickel (Ni) or chromium (Cr) is apparently infrequent, considering their potency and frequent involvement as dermal sensitizers. Metallic dusts deposited in the lung may give rise to pulmonary fibrosis and functional impairment, depending on the fibrogenic potential of the agent and on poorly understood host factors. Inhalation of iron compounds causes siderosis, a pneumoconiosis with little or no fibrosis. Hard metal lung disease is a fibrosis characterized by desquamative and giant cell interstitial pneumonitis and is probably caused by cobalt, since a similar disease has been observed in workers exposed to cobalt in the absence of tungsten carbide. Chronic beryllium disease is a fibrosis with sarcoid-like epitheloid granulomas and is presumably due to a cell-mediated immune response to beryllium. Such a mechanism may be responsible for the pulmonary fibrosis occasionally found in subjects exposed to other metals e.g. aluminium (Al), titanium (Ti), rare earths. The proportion of lung cancer attributable to occupation is around 15%, with exposure to metals being frequently incriminated. Underground mining of e.g. uranium or iron is associated with a high incidence of lung cancer, as a result of exposure to radon. At least some forms of arsenic, chromium and nickel are well established lung carcinogens in humans. There is also evidence for increased lung cancer mortality in cadmium workers and in iron or steel workers.

https://erj.ersjournals.com/content/erj/3/2/202.full.pdf

Metal toxicity and the respiratory tract.

Fetal and early postnatal life represent critical periods in vertebrate immune system development. Disruption of such development by perinatal immunotoxic chemical exposure has been widely described in experimental animal models. The resultant inhibited postnatal immune responses in such animals are often more dramatic and persistent than those after exposure during adult life. Further, recent reports suggest that prenatal exposure to immunotoxicants may exacerbate postnatal aberrant immune responses (e.g., hypersensitivity disorders and autoimmune disease) in genetically predisposed rodents. Limited information is available regarding the possibility of inhibited postnatal immune capacity in humans as a result of developmental immunotoxicant exposure. The multifactorial nature of hypersensitivity and autoimmune responses will further complicate the elucidation of possible relationships between chemical exposure during ontogeny of the human immune system and immune-mediated disease later in life. Taken together, however, the available animal data suggest the potential for altered postnatal immune function in humans exposed to immunotoxicants (e.g., environmental chemicals and therapeutic agents) during fetal and/or early postnatal life.

Development of the murine and human immune system: differential effects of immunotoxicants depend on time of exposure

Most cast dental restorations are made from alloys or commercially pure titanium (cpTi). Many orthodontic appliances are also fabricated from metallic materials. It has been documented in vitro and in vivo that metallic dental devices release metal ions, mainly due to corrosion. Those metallic components may be locally and systemically distributed and could play a role in the etiology of oral and systemic pathological conditions. The quality and quantity of the released cations depend upon the type of alloy and various corrosion parameters. No general correlation has been observed between alloy nobility and corrosion. However, it has been documented that some Ni-based alloys, such as beryllium-containing Ni alloys, exhibit increased corrosion, specifically at low pH. Further, microparticles are abraded from metallic restorations due to wear. In sufficient quantities, released metal ions-particularly Cu, Ni, Be, and abraded microparticles-can also induce inflammation of the adjacent periodontal tissues and the oral mucosa. While there is also some in vitro evidence that the immune response can be altered by various metal ions, the role of these ions in oral inflammatory diseases such as gingivitis and periodontitis is unknown. Allergic reactions due to metallic dental restorations have been documented. Ni has especially been identified as being highly allergenic. Interestingly, from 34% to 65.5% of the patients who are allergic to Ni are also allergic to Pd. Further, Pd allergy always occurrs with Ni sensitivity. In contrast, no study has been published which supports the hypothesis that dental metallic materials are mutagenic/genotoxic or might be a carcinogenic hazard to man. Taken together, very contradictory data have been documented regarding the local and systemic effects of dental casting alloys and metallic ions released from them. Therefore, it is of critical importance to elucidate the release of cations from metallic dental restorations in the oral environment and to determine the biological interactions of released metal components with oral and systemic tissues.

https://journals.sagepub.com/doi/pdf/10.1177/154411130201300108

Biocompatibility of Dental Casting Alloys

Michigan dairy farm residents ate farm products containing polybrominated biphenyls (PBB's) after the accidential contamination of animal feed with the chemical in that state in 1973. The circulating blood lymphocytes of these residents show significant changes. Abnormalities include decreases in the numbers and percentages of peripheral blood lymphocytes that form rosettes with either sheep erythrocytes alone or with sheep erythrocytes sensitized with antibody and complement, increases in lymphocytes with no detectable surface markers ("null" cells), and altered responses to tests designed to evaluate functional integrity of the cells. There appears to be no consistent correlation between the concentration of PBB's in the plasma and the altered lymphocytes. Studies showed that in Wisconsin dairy farm residents and healthy individuals in the New York area who were not exposed to PBB's there were no such abnormalities.

http://science.sciencemag.org/content/sci/199/4334/1207.full.pdf

Lymphocyte function of Michigan dairy farmers exposed to polybrominated biphenyls

One hundred and seventy-eight dental laboratory technicians and 69 non-exposed controls participated in an epidemiological respiratory study. Eight technicians who had a mean of 28 years' grinding nonprecious metal alloys were diagnosed as having a simple pneumoconiosis by chest radiograph. Mean values for per cent predicted FVC and FEV1 were reduced among male nonsmoker technicians compared to male nonsmoker controls; after controlling for age, there was also a reduction in spirometry with increasing work-years. An industrial hygiene survey was conducted in 13 laboratories randomly selected from 42 laboratories stratified by size and type of operation in the Salt Lake City, Utah metropolitan area. Personal exposures to beryllium and cobalt exceeded the Threshold Limit Values (TLVs) in one laboratory. Occupational exposures in dental laboratories need to be controlled to prevent beryllium-related lung disorders as well as simple pneumoconiosis.

https://ajph.aphapublications.org/doi/pdfplus/10.2105/AJPH.74.11.1252

Pneumoconiosis and exposures of dental laboratory technicians.

Chronic beryllium disease is a granulomatous and fibrotic pulmonary disorder with increased numbers and percentage of lymphocytes in bronchoalveolar lavage fluid similar to that found in hypersensitivity pneumonitis. Blastogenic lymphocyte transformation (LT) to beryllium salts has been described in lavage and blood lymphocytes in patients with chronic beryllium disease. We conducted a 3-yr prospective study to evaluate the relationship between LT and beryllium exposure and pulmonary changes consistent with chronic beryllium disease. There were 15.9% (13/82) positive LTs in 1979 and 8.2% (5/61) in 1982. Of 11 positive LTs in 1979, 8 were negative in 1982, concomitant with a significant reduction in exposure. A positive LT was not associated with reduced pulmonary function, and no radiographic changes consistent with beryllium disease were identified. We propose that LT in beryllium workers is related to exposure and is reversible when exposure levels are reduced through diligent industrial hygiene measures.

Reversible Beryllium Sensitization in a Prospective Study of Beryllium Workers

Diseases caused by exposure to asbestos are prime examples of environmentally-related illnesses. Asbestos produces asbestosis from large exposures over short latent periods; it acts as a carcinogen from small exposures over long latent periods; and it induces mesothelioma with minute exposures. Its presence as the magic mineral is ubiquitous in our modern society.

The spectrum of asbestos-related diseases.

A synthetic zeolite and four natural zeolites from the western United States were examined for fibers using a scanning electron microscope. The distributions of fiber sizes were compared to distributions of fiber sizes of erionite and fibrous glass to determine if the fiber sizes were similar to those associated with mesothelioma in humans and animals. Fibers were abundant in two samples of natural erionite, rare in two samples of natural mordenite, and not present in the sample of synthetic mordenite. Although the majority of the erionite fibers were short (less than 8 mu long) and thicker than the tumorigenic erionite (greater than 0.25 mu wide), 6% and 11% of the fibers corresponded to fiber size categories of fibrous glass that have correlated with pleural mesothelioma production in rats. Even a single species of zeolite (erionite) is not uniform in its distribution of fiber sizes. On the basis of fiber size, these natural zeolites should be evaluated because of their potential carcinogenic risk.

William N. Rom

Papers

Lymphocyte function of Michigan dairy farmers exposed to polybrominated biphenyls

Pneumoconiosis and exposures of dental laboratory technicians.

Reversible Beryllium Sensitization in a Prospective Study of Beryllium Workers

The spectrum of asbestos-related diseases.

Characterization of zeolite fiber sizes using scanning electron microscopy.