Abstract  1-Bromopropane was introduced as an alternative to ozone layer-depleting solvents such as chlorofluorocarbons and 1,1,1-trichloroethane. However, a dozen human cases have been reported with symptoms and signs of toxicity to 1-bromopropane including numbness, diminished vibration sense in the lower extremities as well as ataxic gait. An epidemiological study also demonstrated dose-dependent prolongation of distal latency and decrease in vibration sense in the lower extremities. The initial animal experiments helped to identify and analyze the initial human case of 1-bromopropane toxicity. However, animal data that can explain the central nervous system disorders in humans are limited. Nonetheless, animal data should be carefully interpreted especially in a high-order function of the central nervous system or neurological signs such as ataxia that is influenced by fundamental anatomical/physiological differences between humans and animals. Enzymatic activity in the liver may explain partly the difference in the susceptibility between humans and animals, but further studies are needed to clarify the biological factors that can explain the difference and commonality among the species.

Abstract  Occupational exposure to the solvent 1-Bromopropane (1-BP) used in degreasing, dry cleaning, spray adhesives, and aerosol solvents has been linked to neurological illnesses.

Abstract  1-Bromopropane (1-BP) is a solvent that is used in degreasing, dry cleaning, spray adhesives, and aerosol solvents. Occupational exposure to 1-BP has been linked to neurological illnesses. Animal studies show that 1-BP may also cause cancer and reproductive disorders. Controls and personal protective equipment are available to protect workers from 1-BP exposure. Exposure to 1-BP can cause irritation (for example, of the eyes, mucous membranes, upper airways and skin) and can damage the nervous system. Neurologic effects can appear as headaches, dizziness, loss of consciousness, slurred speech, confusion, difficulty walking, muscle twitching, and/or loss of feeling in arms and legs (Ichihara et al. 2012). These effects may continue among affected persons even after exposure to 1-BP has ended (Majersik et al. 2007). As with many other solvents, workers can be exposed to 1-BP by breathing in vapor or mists of spray. Workers might also be exposed if the chemical touches their skin because it can be absorbed (Hanley et al. 2006; Frasch et al. 2011). Additionally, the risk of health effects to workers increases the longer they work with or near 1-BP. Impacts on health have been seen in workers after exposures for as little as two days, although symptoms are more commonly associated with longer exposure (Ichihara et al. 2012). Federal OSHA does not currently have a specific exposure standard for 1-BP; however, employers are required by law to keep their workers safe from this recognized hazard. Degreasing, spray adhesive, aerosol solvent and dry cleaning operations expose workers to air concentrations of 1-BP greater than the limits set by the California Occupational Safety and Health Administration (Cal-OSHA) and the American Conference of Governmental Industrial Hygienists (ACGIH). California has adopted a 5 ppm (parts per million) time-weighted average PEL (permissible exposure limit) along with a skin notation which means that a worker's skin, eyes and mouth should be protected from any contact with 1-BP; this limit was based on reproductive and developmental toxicity (observed in animal studies) and technological feasibility assessments from industry (CA DIR 2009). ACGIH currently recommends a 10 ppm time-weighted average threshold limit value but has proposed lowering the value to 0.1 ppm (ACGIH 2013).

Abstract  Cytochromes P450 (CYPs) comprise a number of enzyme subfamilies responsible for the oxidative metabolism of a wide range of therapeutic agents, environmental toxicants, mutagens, and carcinogens. In particular, cytochrome P450 2E1 (CYP2E1) is implicated in the oxidative bioactivation of a variety of small hydrophobic chemicals including a number of epoxide-forming drugs and environmentally important toxicants including urethane, acrylamide, acrylonitrile, benzene, vinyl chloride, styrene, 1-bromopropane, trichloroethylene, dichloroethylene, acetaminophen, and butadiene. Until recently, chemical modulators (inducers and inhibitors) were used in order to characterize the enzymatic basis of xenobiotic metabolism and the relationships between CYP-mediated bioactivation and chemical-induced toxicity/carcinogenicity. With the advent of genetically engineered knockout mice, the ability to evaluate the roles of specific CYPs in the metabolism of xenobiotics has become more attainable. The main focus of the current review is to present studies that characterized the enzymatic, metabolic, and molecular mechanisms of toxicity, genotoxicity, and carcinogenicity of various xenobiotics using Cyp2e1-/- mice. Data presented in this review demonstrated that the most comprehensive studies using Cyp2e1-/- mice, encompassing the entire paradigm of metabolism to toxicity, genotoxicity, and carcinogenicity were possible when a substrate was primarily metabolized via CYP2E1 (e.g. urethane and acrylamide). In contrast, when multiple CYP enzymes were prevalent in the oxidation of a particular substrate (e.g.: trichloroethylene, methacrylonitrile, crotononitrile), investigating the relationships between oxidative metabolism and biological activity became more complicated and required the use of chemical modulators. In conclusion, the current review showed that Cyp2e1-/- mice are a valuable animal model for the investigation of the metabolic and molecular basis of toxicity, genotoxicity, and carcinogenicity of xenobiotics.

Abstract  The fact that a conference on neurotoxicity was held in China triggered the idea to provide an insight into occupational diseases, their development and the approaches to investigate them in Asian countries. A historical review, a meta-analysis, and studies on humans and animals provide impressions on past and current problems. The Korean example showed that each newly introduced industry is accompanied by its own problems as regards occupational diseases. Mercury and carbon disulfide were of importance in the beginning, whereas solvents and manganese became important later. Outbreaks of diseases were important reasons to guide both the public and the governmental attention to prevention and allowed within a relatively short time considerable progress. As the example on the replacement of 2-bromopropane by 1-bromopropane showed, also the introduction of chemicals that are more beneficial for the environment may result in additional occupational risks. A lower mutagenicity of 1-bromopopane was shown to be associated with a greater neurotoxicity in Japanese studies. Although occupational health and diseases are commonly related to adults, child workers exposed to solvents were examined in a Lebanese study. The study started outlining the health hazards in young workers because they might be at a much greater risk due to the not yet completed maturation of their nervous system. That some occupational diseases are not yet a focus of prevention was shown by the study on pesticides. If at all, the serious health consequences resulting from excessive exposure were investigated. Research enabling precautionary actions was not available from the international literature. Despite globalization the knowledge on occupational diseases is not yet "globalized" and each country obviously undergoes its own development triggered by local experiences. Economic development that requires a healthy workforce, but also public interest that challenges governmental regulations further efforts on the prevention of occupational diseases. The paper reflects a summary of the talks presented at the symposium "Occupational Neurotoxicities in Asian Countries" as part of the 11th International Symposium on Neurobehavioral Methods and Effects in Occupational and Environmental Health.

Abstract  We aimed to better understand the pathogenesis, clinical features, prognosis, and treatment of neonatal autoimmune blistering diseases (AIBDs). We searched Medline, Embase, PubMed, Latin American and Caribbean Health Sciences Literature, and reference lists of identified articles. Inclusion criteria were articles published from 1946 to December 2014 in any language. Exclusion criteria were age greater than 4 weeks and no confirmed AIBD diagnosis. We identified 51 cases of neonatal AIBDs: 34 cases of pemphigus (31 pemphigus vulgaris [PV], 3 pemphigus foliaceus [PF]) and 17 cases of pemphigoid diseases (9 bullous pemphigoid [BP], 5 linear immunoglobulin A bullous dermatosis [LABD], 1 BP and LABD, 1 epidermolysis bullosa acquisita, 1 bullous systemic lupus erythematosus). Pemphigoid diseases had a higher male predominance (male:female ratio 4.6:1) than pemphigus (male:female ratio 1:1.06) (p = 0.004). Pemphigus had a higher proportion presenting at birth (79.4%) than pemphigoid diseases (29.4%) (p = 0.008). The most common sites involved were the trunk (63.0%), followed by the head and neck (60.9%). The mucosal membranes were involved in 32.6% of cases (27.6% in pemphigus, 41.6% in pemphigoid diseases). Only 33.3% used systemic therapy, and 75.5% achieved control within 3 weeks. Most PV, PF, and BP cases, but not LABDs, reported maternal disease. In pemphigus cases, 75.0% of mothers had active disease and 25.0% were in control. Pregnant women with PV, PF, and PG of any severity can passively transfer autoantibodies leading to neonatal AIBD. Pemphigoid diseases are more likely to present after birth and may be more male predominant. The presentation of LABDs may be different from that of all other AIBDs.

Abstract  INTRODUCTION 1-Bromopropane (n-propyl bromide, CASRN 106-94-5) is a brominated hydrocarbon that is currently used as a solvent in a variety of industrial and commercial applications. Exposure to workers has been increasing in the past few years due to several new applications in which 1-bromopropane has been substituted for substances identified as suspect carcinogens or ozone-depleting chemicals. The available occupational exposure data indicate that workers can be exposed to high levels of 1-bromopropane. 1-Bromopropane was selected as a candidate substance for the Report on Carcinogens (RoC) due to the potential for substantial human exposure to 1-bromopropane in the United States, and an adequate database to evaluate its potential carcinogenicity. 1-Bromopropane has been tested for carcinogenicity in rodents in a 2-year inhalation study (NTP 2011a). In addition, 1-bromopropane causes toxicity in people and experimental animals. Structurally related haloalkanes are carcinogenic in experimental animals.