Neuro-reproductive toxicity and carcinogenicity of 1-bromopropane: studies for evidence-based preventive medicine.

Abstract

Bromopropane was introduced commercially as an alternative to ozone-depleting and global-warming solvents. The identification of 1-bromopropane neurotoxicity in animal experiments was followed by reports of human cases of 1-bromopropane toxicity. In humans, the most common clinical features of 1-bromopropane neurotoxicity are decreased sensation, weakness in extremities, and walking difficulties. Moreover, decreased cognition, abnormal findings on brain magnetic resonance imaging, urinary incontinence, and numbness in the perineal area have also been described in workers exposed to 1-bromopropane. Murine histological studies showed that exposure to 1-bromopropane reduced the density of brain noradrenergic axons. Furthermore, proteome studies demonstrated 1-bromopropane-induced changes in the expression of proteins in the hippocampus of rats, similar to the changes seen in mice exposed to acrylamide, suggesting a common mechanism of electrophile-induced neurotoxicity. In addition to its neurotoxicity, 1-bromopropane also induces male reproductive toxicity in rats, although the targeted areas in the reproductive system differ from those affected by 2-bromopropane. However, exposure to high levels of 1-bromopropane was reported to induce spermatogenic cell degeneration, similar to that caused by 2-bromopropane, suggesting common mechanism(s) underlying 1- and 2-bromopropane-induced male reproductive toxicity. Plural approaches, including human, animal, and mechanistic studies, are useful for identification of 1-bromopropane neurotoxicity. The International Agency for Research on Cancer summarized that 1-bromopropane as well as 2-bromopropane share several key characteristics of carcinogens. Plural approaches can establish evidence-based preventive medicine by modification of the conventional evidence-based medicine (EBM), which has been developed for therapeutic medicine and is represented by the EBM pyramid.