| Background and Objective1-bromopropane(1-BP), with the characteristic of high volatility, difficult to burn and low ozone depletion potential, is widely available in the industries of electronic products,vehicles, aircrafts and household machines etc, currently. With the increasing production and use of 1-BP year by year, people who would access 1-BP are also increased. The main exposure route of 1-BP is inhaled through respiratory tract in the occupational activities or skin contact which would lead to chronic poisoning. There is no report that people get poisoning through ordinary contacts such as air, water and food by 1-BP. Since 1999 home and abroad have discovered several cases of occupational poisoning of 1-BP. Through experimental animals and occupational exposure of human cases study, the National Toxicology Program evaluated the chronic health effects of 1-BP, and 1-BP was listed as the Potential Carcinogenic.1-BP has toxicological effects on multiple systems of the body. And the toxicological effects of 1-BP on the nervous and reproductive systems are the most significant, but the toxicological effects on liver and blood system are also cannot be ignored. Current case reports and animal experimental studies have confirmed the neurotoxicity, reproductive toxicity and general toxicity of 1-BP, but research data is still not systematic enough. The toxicity mechanism of 1-BP mainly concentrates on the neurotoxicity and reproductive toxicity. But the toxicological effects and mechanisms of 1-BP on other organs, such as liver and blood, are still unclear. Although many studies have conducted on rats and mice,no study data or similar toxicological effects on rabbits is reported. Therefore, a study of1-BP on SD rats and New Zealand rabbits, with two different ways of exposure will contribute to reveal the further toxicological effects of 1-BP, which will provide a more comprehensive understanding on organisms and their mechanisms, and also the biological markers of 1-BP. The study data will provide a theoretical basis for the occupational health protection and occupational health monitoring of 1-BP, so as to protect the health of workers more effectively.Methods1. Study Methods1.1 Toxicity Study of 1-BP in Sprague Dawley(SD) Rats30 Specific Pathogen Free(SPF) SD male rats were randomly divided into three groups:a control, a test and an additional-test group. Each group was carried out with 10 male rats.Test and additional-test groups of rats were conducted by intraperitoneal injection with1-BP with a dose of 1000 mg/kg.b.w and the volume of 3.0 m L/kg, and were injected every two days and 3 times a week. Control group was carried out with corn oil by intraperitoneal injection at the volume 3.0 m L/kg. Except for the test substance(1-BP), the injection method and cycle of control group were the same with the study groups. During the study,all rats were needed to record their body weight, how much water and feed the rats consumed. All the rats were injected for consecutive 14 weeks. At medium and last of the study, all the rats were put into the metabolic cages to collect their urine and ICP-MS method were used to test the total bromine content of the urine. The next day after the rats were injected at last of the study, The rats of the test and control were taken to weight their bodies then were carried out with pentobarbital sodium anesthesia. Afterwards, the rats were killed with abdominal aortic blood collection to do haematology and biochemistry test.Then, the rats were anatomised and their main organs were weighted to calculate the organ coefficients. At the same time, their organs were conducted to do histopathological examinations. The additional-test group continued to be observed for 3 weeks after the rats stopped being injected with 1-BP, so that the reversibility, persistence and delay of the toxicity of 1-BP were observed.1.2 Toxicity Study of 1-BP in New Zealand Rabbits12 general female New Zealand rabbits were randomly divided into a control group and an test group according to their body weight. The control and test groups was carried out with 4 and 8 animals respectively. Test group rabbits were carried out by subcutaneous injections with 1-BP. with a dose of 500 mg/kg. b.w and the dose volume of 1.0 m L/kg for every two days and 3 times a week. Control group were subcutaneously injected with a volume of 1.0 m L/kg corn oil. Apart from the different test subject(1-BP), the injection method and time in control group were the same with test group. During the study, all rabbits were needed to record their body weight and the feed consumption of the rabbits.All the rabbits were injected for consecutive 15 weeks. At medium and last of the study, all the rabbits were conducted to collect their blood from ear marginal vein to do haematology and biochemistry test. ICP-MS method were used to test the total bromine content of serum too. The next day after the rabbits were injected at last of the study, they were taken to weight their bodies then were carried out with pentobarbital sodium anesthesia. Afterwards,the rabbits were killed with abdominal aortic blood collection. Then, the rabbits were anatomised and their main organs were weighted to calculate the organ coefficients. At the same time, their organs were conducted to do histopathological examinations.2. Statistical analysisFor the test and control groups, their body weight, haematology, biochemistry, organ weight and other quantitative data were analysed with two independent samples of Jonckheere-Terpstra Test. Feed and water consumptions were analysed with randomized block design of variance, while the result of pathological changes of the viscera and other count data were analysed with chi-square test; the test level of a = 0.05. Graph Pad Prism 5software was used for study data mapping; LEICA DFC405 C was used for pathological Image analysis.Results1. The general toxicity effect of animals exposed to 1-BP1.1 The general symptoms of animals1.1.1 The rats of test group were observed having less activity, filthy clothing hair, poor spirit and getting body weight loss after the exposure of 1-BP.1.1.2 The rabbits of test group were observed having less activity, poor spirit and getting body weight loss after the exposure of 1-BP.1.2 The consumption of feed and water1.2.1 The average daily consumption of feed was significantly decreased in the test group of rats, compared with that of the control group(P<0.01).1.2.2 The average daily consumption of feed was significantly decreased in the test group of rabbits, from ninth weeks to the end of test, except for the twelfth week, compared with that of the control group(P<0.05 or P<0.01).1.3 Effects of body weight of animals exposed to 1-BP1.3.1 After they were exposed to 1-BP for 2 weeks, body weight of test group of rats was decreased, compared with that of the control group(P<0.05 or P<0.01).1.3.2 The average weekly body weight gain of test group of rats was significantly decreased,compared with that of the control group(P<0.01).1.3.3 After they were exposed to 1-BP for 7 weeks, body weight of test group of rabbits was decreased, compared with that of the control group(P<0.05 or P<0.01).1.3.4 The average weekly body weight gain of test group of rabbits was significantly decreased, compared with that of the control group(P<0.01).2. The organ examination of animals exposed to 1-BP2.1 Effects of organ weight of animals exposed to 1-BP2.1.1 The organ weight of brain, testis and epididymis of test group of rats was decreased,compared with that of the control group(P<0.05 or P<0.01).2.1.2 The organ weight of uterus of test group of rabbits was decreased, compared with that of the control group(P<0.05).2.2 Effects of organ coefficients of animals exposed to 1-BP2.2.1 The coefficients of brain, testis and epididymis of test group of rats were decreased,compared with that of the control group(P<0.05 or P<0.01).2.2.2 The coefficients of liver of test group of rats were significantly increased, compared with that of the control group(P<0.01).2.2.3 The coefficients of uterus of test group of rabbits were decreased, compared with that of the control group(P<0.05).2.2.4 The coefficients of liver of test group of rabbits were increased, compared with that of the control group(P<0.01).3. The results of hematologic test of animals exposed to 1-BP3.1 The results of haematology test of animals exposed to 1-BP3.1.1 The hematocrit(HTC) and hemoglobin concentrations(HGB) of test group of rats were decreased, compared with that of the control group(P<0.05).3.1.2 The platelet distribution width(PDW), platelet count(PLT), mean platelet volume(MPV) and plateletcrit(PCT) were increased, compared with that of the control group(P<0.05 or P<0.01).3.1.3 After 15 weeks of exposure to 1-BP, the thrombocytocrit(PCT) and platelet count(PLT) of test group of rabbits was increased, compared with that of the control group(P<0.05).3.2 The results of biochemistry test of animals exposed to 1-BP3.2.1 The creatine kinase(CK) of test group of rats were decreased, compared with that of the control group(P<0.01).3.2.2 After 8 weeks of exposure to 1-BP, the creatine kinase(CK) of test group of rabbits was increased, compared with that of the control group(P<0.01).4. The results of total bromine content of animals exposed to 1-BP4.1 The results of the total bromine content in rats urineAfter 7-week and 14-week periods of exposures to 1-BP respectively, total bromine content of rats urine of test group in both periods were significantly increased, compared with that of the control group(P<0.01).4.2 The results of the total bromine content in New Zealand rabbit serum4.2.1 After 8-week and 15-week periods of exposures to 1-BP respectively, total bromine content in rabbit serum of the test group in both periods were significantly increased,compared with that of the control group(P<0.01).4.2.2 Total bromine content of 15-weeks-exposur in rabbit serum of test group were significantly increased, compared with that of the 8-weeks-exposur(P<0.01).Conclusions1. Exposed to 1-BP could cause liver toxicity and reproductive. The liver, uterus and testis/epididymis were the important target organs of toxicological effects of 1-BP.Moreover, 1-BP had certain blood toxicity, which could cause anemia and blood coagulation dysfunction.2. The Four Parameters of Platelet(PDW, PLT, MPV, PCT) and the Creatine Kinase(CK)may be as toxicological biomarkers of 1-BP.3. Total bromine content of urine and serum was sensitive to the exposure of 1-BP, and they could be sensitive indicators, which could be used as initial screening biomarkers of1-BP exposure. |
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