Inorganic bromide is widely distributed in nature. Its natural physiological role in animal life is unknown. More than a century ago bromide was introduced in medicine as an antiepileptic drug. Nowadays, man is primarily exposed to bromide via food as the result of use of bromide-containing fumigants in intensive horticulture and in the treatment of food stocks. In this review exposure of man to bromide is described, and the pharmacological and toxicological effects of bromide ion are discussed.

At present, we are unable to use much of the data derived from alternative (non-animal) tests for human health risk assessment. This brief Comment outlines why it is plausible that new paradigms could be developed to enable risk assessment to support consumer safety decisions, without the need to generate data in animal tests. The availability of technologies that did not exist 10 years ago makes this new approach possible. The approach is based on the concept that data and information derived from applying existing and new technologies to non-animal models can be interpreted in terms of harm and disease in man. A prerequisite is that similar data and information generated in a clinical setting are available to permit this “translation”. The incorporation of this additional translation step should make it possible to use data and information generated in non-animal models as inputs to risk assessment. The new technologies include genomics, transcriptomics, proteomics and metabonomics. Their application to in vitro and human “models” enables large amounts of data to be generated very quickly. The processing, interpretation and translation of these data need to be supported by powerful informatics capabilities and statistical tools. The use of integrated “systems biology” approaches will further support the interpretation by providing better understanding of the underlying biological complexity and mechanisms of toxicity. Clinical medicine is using the opportunities offered by the new ‘omics’ technologies to advance the understanding of disease. The application of these technologies in clinical medicine will generate massive amounts of data that will need processing and interpretation to allow clinicians to better diagnose disease and understand the patients’ responses to therapeutic interventions. Support from clinical epidemiology will be essential. If these data and information can be made generally accessible in an ethical and legal way, they should also permit the “translation” of experimental non-animal data, so that they can then be used in risk assessment.

1 In previous studies a rat inhalation model was developed to investigate the treatment of acute nitrogen dioxide (NO2) intoxication. 2 Biochemical parameters, which may be important for the evaluation of lung injury and repair, were reviewed and compared with the histology. 3 After exposure to high NO2 concentrations (75 ppm, 125 ppm or 175 for 10 min) 1 the lung injury observed by light microscope was most pronounced after 24 h and became worse with increasing concentration. 4 The most sensitive indicators for lung injury in the broncho-alveolar lavage fluid (BAL) were protein and albumin concentrations, angiotensin converting enzyme activity, β-glucuronidase activity and the presence of neutrophil leucocytes. The changes observed in these variables were dose-dependent. Following exposure to 175 ppm the protein and albumin concentrations and the angiotensin converting enzyme activity showed a 100-fold increase, while the β-glucuronidase activity showed a 10-fold increase. 5 Glucose-6-phosphate dehydrogenase and glutathione peroxidase in the supernatant of lung homogenate and gamma-glutamyl transferase activity in BAL are likely to be the most practical parameters for monitoring the phase of repair because their activities were maximal at the moment histological changes were reduced in intensity. 6 Repair was almost complete 7 d following exposure.

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1 The effects of exposure of the skin to high concentrations of methyl bromide were studied in 6 cases, who had been unintentionally exposed. 2 Exposure to high concentrations of methyl bromide (approximately 40 g/m3) for 40 min can lead to redness and blistering of the skin. This cannot be prevented by wearing standard protective clothing. 3 Skin lesions show a preference for relatively moist skin areas. 4 Plasma bromide levels were highest immediately following exposure (mean 9.0 ± 1.4 mg/l) and fell in subsequent hours (mean 6.8 ± 2.3 mg/l 12 h after the exposure), suggesting absorption of (methyl) bromide through the skin. 5 No systemic effects were noted in this series. 6 Fumigation with methyl bromide should not be done in such a way as to require the presence of workers inside closed areas, where methyl bromide is released.