1-溴丙烷对两种雄性大鼠生殖毒性的研究

目的研究1-溴丙烷对两种雄性大鼠的生殖毒性。方法将18只Fischer344大鼠和18只Wistar大鼠分别随机分为两组,一组给予新鲜空气,一组给予1000ppm1-溴丙烷,每天8h,连续暴露4周。在显微镜下对附睾的精子活动率和形态进行评价;睾丸等生殖器官进行了病理学评价。结果1-溴丙烷的暴露可引起大鼠的体重及生殖器官重量的下降;附睾的精子数减少、活动率下降、形态异常的精子增多;睾丸病理切片观察到曲精小管的精子释放延迟以及附睾的病理变化。结论1-溴丙烷暴露对两种雄性大鼠的生殖系统产生毒性影响,提示1-溴丙烷也可能对男性工人生殖系统产生不良影响。     

1-溴丙烷吸入暴露对雄性大鼠生殖系统的影响

目的研究1-溴丙烷亚急性暴露对雄性大鼠的生殖毒性.方法将48只雄性大鼠分为对照组、1-溴丙烷1 000、2000、4000 mg/m3暴露组.暴露组给予7 d,每天8 h的吸入暴露.结果1-溴丙烷高浓度暴露组大鼠的体重、前列腺和精囊质量显著下降,附睾精子运动率降低,形态异常精子增多.血浆肌酸激酶活力和肌型肌酸激酶含量降低.睾丸病理切片观察到曲细精管的精子释放延迟.结论1-溴丙烷亚急性暴露对雄性大鼠的生殖系统产生毒性影响,附睾精子运动率的下降是本次实验的最敏感指标.     

溴丙烷两种同分异构体对大鼠肝脏毒性的影响

目的 了解溴丙烷(BP)2种同分异构体(1-BP和2-BP)对雄性大鼠肝脏的影响.方法 18只雄性大鼠随机分为对照组(玉米油)、1-BP组(1g/kg)和2-BP组(1g/kg),每组6只,每日1次腹腔注射,连续注射1周后进行肝组织病理学及细胞凋亡观察,并利用化学比色法测定谷胱甘肽(GSH)、谷胱甘肽还原酶(GSH-RD)、谷胱甘肽过氧化物酶(GSH-Px)和谷胱甘肽转移酶(GST)活力;检测肝脏的细胞凋亡和Caspas-3活力.结果 1-BP组大鼠体重(264.83±8.04)g,与对照组[(288.50±23.93)g]比E较,差异有统计学意义(P＜0.05);2个BP组大鼠肝组织均出现细胞核体积缩小且皱缩变形,且有不同程度的肝细胞空泡变性;各组GSH、GSH-RD、GSH-Px和GST活力比较,差异无统计学意义(P＞0.05).1-BP组阳性凋亡细胞数为(15.40±6.04),明显高于对照组和2-BP组,差异有统计学意义(P＜0.05);1-BP组大鼠肝细胞胞质巾可见Caspase-3阳性的棕褐色颗粒,对照组和2-BP组肝细胞胞质中较少见到Caspase-3阳性的棕褐色颗粒.结论 溴丙烷2种同分异构体的短期暴露均可引起大鼠肝脏病理变化,但肝细胞凋亡程度有差异.     

溴丙烷两种同分异构体对雄性大鼠生殖系统的影响

目的了解溴丙烷两种同分异构体对雄性大鼠的生殖毒性和初步的毒性机制。方法将18只SPF级SD大鼠随机分为对照组、1-溴丙烷组(1g/kg)和2-溴丙烷组(1g/kg),连续腹腔注射1周。对附睾的精子数量和形态进行评价;HE和PAS染色评价睾丸的病理变化;运用TUNEL染色法和caspase-3活性的免疫组化法评价睾丸的细胞凋亡损伤;利用化学比色法对谷胱甘肽(GSH)、丙二醛(MDA)和超氧化物歧化酶(SOD)等氧化应激指标进行测量。结果溴丙烷导致睾丸重量下降、精子数量减少和精子形态异常比例增加。与对照组比较,1-溴丙烷显著增加大鼠睾丸谷胱甘肽还原酶(GR)活性(7.42±2.98vs.4.25±1.18)、附睾的MDA含量(0.49±0.20vs.0.39±0.08)和SOD活性(91.87±3.93vs.80.59±9.92)(均P0.05);2-溴丙烷显著升高睾丸和附睾的MDA含量(0.42±0.07vs.0.24±0.11;0.48±0.08vs.0.39±0.08),降低GSH含量(6.35±1.86vs.10.89±3.69),以及附睾谷胱甘肽转移酶(GST)(53.21±9.60vs.61.98±10.41)及GR活性(2.48±1.21vs.7.75±8.56)(均P0.05)。1-溴丙烷的病理切片除观察到睾丸生精小管的精子释放延迟外,未见其他病理变化,而2-溴丙烷的暴露使生精小管出现萎缩和空泡,生殖细胞发生减少、坏死。伴随着2-溴丙烷引起的睾丸病理变化,TUNEL标记结果显示每小管睾丸凋亡细胞数、凋亡百分比和凋亡指数明显高于对照组(17.72±4.59vs.5.92±1.05,P0.05;0.34±0.14vs.0.10±0.02,P0.05;6.64±3.40vs.0.59±0.20,P0.01),与1-溴丙烷组相比,凋亡百分比(0.34±0.14vs.0.12±0.03)和凋亡指数(6.64±3.40vs.0.76±0.21)明显升高(P0.05)。2-溴丙烷暴露使caspase-3活性增强,与对照组和1-溴丙烷组相比,平均每生精小管的阳性细胞数和caspase-3阳性百分比有明显的升高(均P0.01)。结论溴丙烷的两种同分异构体对雄性大鼠有一定的毒性,两种同分异构体可能具有不同的毒性机制,2-溴丙烷的毒性可能高于1-溴丙烷。     

1—溴丙烷工厂工人健康状况调查及接触生物标记物的研究

目的 分析1-溴丙烷毒性并评价其危险度，探讨适宜的接触生物标记物，方法 对37名工人进行问卷调查。血液学指标和血生化指标的测定。包括垂体激素和性激素测定。以该工厂工人为接触组，食品厂工人为对照组，比较两组间的血浆，脶酸激酶（CK）活性和血浆肌酸激酶M亚基（CK-M）。尿中1-溴丙烷用气相色谱仪检测，个体暴露蓄积水平用个体采样器估测。结果 接触组工人出现眼，鼻，口腔，喉的粘膜刺激症状。部分工人出现眩晕，可能是神经系统的反应。结论 接触1-溴丙烷引起的主诉症状提示它能刺激上呼吸道粘膜，在约100mg/m^3浓度水平可影响中枢神经系统，尿1-溴丙烷浓度有望成为接触的生物标记物。     

1-溴丙烷神经毒性作用机制及生物标志研究进展

1-溴丙烷因其特有的化学性质成为可对臭氧层造成破坏的一类清洗剂的理想替代产品,广泛应用于精密仪器清洗等生产领域。1-溴丙烷具有神经毒性、生殖毒性和肝毒性,其中以神经毒性最为显著。本文从1-溴丙烷主要代谢酶、蛋白质组学技术和神经元损伤等几方面,分析了1-溴丙烷对神经系统毒性作用的可能机制及典型的生物标志。     

甜菜和洋白菜饲料对黄曲霉毒素B_1诱发大鼠血浆甲胎蛋白升高、致肝脏肿瘤和尿致突变作用的影响

作者用大鼠研究观察二种蔬菜(甜菜和洋白菜)饲料对黄曲霉毒素B_1(AFB_1)诱发大鼠肝癌的影响。将60只断乳雄性F344 Fischer大鼠分成基础、甜菜和洋白菜膳食组,各组再分为加和不加1 ppm AFB_1组,共6个组。甜菜和洋白菜组各加入25%(W/W)的冷冻干燥磨碎的食用甜菜或洋白菜,并加入酪蛋白和碳水化     

1-溴丙烷引发雄性大鼠性腺基因表达谱的变化

目的研究1-溴丙烷(1-BP)诱发大鼠性腺基因表达谱的变化,探索1-BP雄性生殖毒性相关的mRNA改变。方法雄性F344/NSIc大鼠12只,随机分为2组,分别吸入新鲜空气或5030mg/m31-BP8h。染毒后16h处死大鼠取出睾丸,运用大鼠性腺cDNA微阵列和real-timePCR方法测定1-BP染毒后性腺相关基因表达谱的变化。结果在大鼠性腺芯片5087个cDNA微点阵中,有62个基因被1-BP显著下调,3个基因显著上调。其中包括性激素合成相关基因细胞色素P450芳香化酶(CYP19a),谷胱苷肽S-转移酶(GSTT1),肌酸激酶(Ckb),髓鞘和淋巴细胞蛋白(Mal)和S100的钙结合蛋白(S100a4)。归类分析结果显示绝大多数变化的基因与蛋白质/脂类代谢相关,其次与应激防御反应相关。实时定量PCR证实了1-BP可引起CYP19a、S100a4、GSTT1和Mal的下调。结论急性高剂量染毒1-BP可引起睾丸组织CYP19a、S100a4、GSTT1、Mal等基因的下调,提示其可能通过内分泌干扰和氧化应激效应而导致雄性生殖毒性。     

大蒜对酒精摄入致小鼠亚慢性肝毒性保护作用的探讨

[目的]研究大蒜对亚慢性酒精中毒肝毒性的保护作用及其可能机制。[方法]对60只清洁级ICR雄性小鼠随机分为6组:阴性对照组,酒精肝模型组,酒精 低、中、高剂量大蒜水提取液干预组和维生素E组。干预28天后,处死小鼠,测定相关指标。[结果]亚慢性酒精摄入可致小鼠血清ALT、AST的活力降低,肝匀浆γ-GGT活力受抑;提高肝脏组织MDA含量,抑制GSH-Px酶活力,消耗GSH,并降低SOD酶活力。中高剂量组可部分拮抗AST活力降低,恢复γ-GGT活力水平;抑制肝体系数的升高和肝细胞水肿、脂肪变及坏死;降低肝组织MDA含量,恢复GSH-Px和SOD酶活力,提高GSH含量和增强GST活力。维生素E仅能恢复γ-GGT活力,降低肝组织MDA含量,升高SOD酶活力。[结论]预先给予大蒜对亚慢性酒精摄入致肝毒性有良好拮抗作用,抗氧化作用是大蒜拮抗亚慢性酒精摄入所致肝脏损伤的重要机制,其中GSH解毒体系具有重要意义。     

铝氟暴露对大鼠血清脂质过氧化反应的影响

目的 探讨铝氟联合暴露对大鼠抗氧化酶活力和脂质过氧化代谢的影响及其动态改变。方法86只雄性SD大鼠按体质量随机分为9组,氯化铝按105、35和0mg/kg,氟化钠按18、3和0mg/kg剂量三水平交叉实验设计,于实验4、8和11周分别采用硫代巴比妥酸法（TBA法）测定血清丙二醛（MDA）含量;黄嘌噙氧化酶法测定越氧化物歧化酶（SOD）活力;二硫代二硝基苯甲酸法（DTNB）测定谷胱甘肽过氧化物酶（GSH-Px)的活力。结果 铝和氟暴露的确引起大鼠抗氧化酶活力和脂质过氧化产物含量的改变,表现为铝氟暴露引起x活力升高,且与铝,氟存在剂量-反应关系,动态观察结果提示SOD急性期（4周）反应强烈,活力处于高水平,亚急性或慢性期（8-11周）降低并趋于稳定。结论 铝氟暴露确能引起大鼠抗氧化酶活力改变和脂质过氧化代谢紊乱,脂质过氧化所致辞损伤可能是铝氟毒性重要机制。值得进一步探讨。     

Neuro-reproductive toxicities of 1-bromopropane and 2-bromopropane

2-Bromopropane was used as an alternative to chlorofluorocarbons in a Korean electronics factory and caused reproductive and hematopoietic disorders in male and female workers. This causality was revealed by animal studies, and target cells were identified in subsequent studies. After identification of 2-bromopropane toxicity, 1-bromopropane was introduced to the workplace as a new alternative to ozone-depleting solvents. 1-Bromopropane was considered less mutagenic than 2-bromopropane, but, in contrast, animal experiments revealed that 1-bromopropane is a potent neurotoxic compound compared with 2-bromopropane. It was also revealed that 1-bromopropane has reproductive toxicity, but the target cells are different from those of 2-bromopropane. Exposure to 1-bromopropane inhibits spermiation in male rats and disrupts the development of follicles in female rats, in contrast to 2-bromopropane, which targets spermatogonia and oocytes in primordial follicles. After the first animal study describing the neurotoxicity of 1-bromopropane, human cases were reported. Those cases showed decreased sensation of vibration and perception, paresthesia in the lower extremities, decreased sensation in the ventral aspects of the thighs and gluteal regions, stumbling and headache, as well as mucosal irritation, as the initial symptoms. The dose–response of bromopropanes in humans and mechanism(s) underlying the differences in the toxic effects of the two bromopropanes remain to be determined.     

Investigation of toxicity through human cases and animal experiments--study of bromopropanes

In 1995, workers in a Korean electronic factory exhibited oligospermia or amenorrhea. We investigated the toxicity of 2-bromopropane used as an alternative to chlorofluorocarbons in the factory in animal experiments, and clarified that exposure to 2-bromopropane depletes spermatogenic cells in male rats and oocytes in female rats. Subsequently, we investigated the neurotoxicity of 2-bromopropane on the basis of the reported neuropathy in the Korean workers exposed to 2-bromopropane. For comparison, we employed 1-bromopropane, which is now used as a new alternative to chlorofluorocarbons. The results showed that 1-bromopropane is more neurotoxic than 2-bromopropane, causing harm to reproductive organs by inhibiting spermiation in the testis and impairing follicular development in the ovary. Shortly after the initial investigation of 1-bromopropane in animals, human cases were reported in the United States. Neurologic abnormalities in Chinese workers exposed to 1-bromopropane were also reported, such as the elongation of distal latency and lowered sense of vibration in the lower limbs. Thus, these serial studies revealed that 1-bromopropane is neurotoxic, but its dose-response relationship in humans remains unknown. In the investigation of 2-bromopropane toxicity, initial animal studies were designed on the basis of human studies, while in research on 1-bromopropane, animal studies preceded human studies and contributed to the prediction of toxicity in humans. However, the use of animal model is limited in its ability to predict the toxicity of chemicals introduced depending on species differences. Further studies should focus more on the differences and commonality between animals and humans in response to toxic agents.     

Diffusive Sampling and Biological Monitoring of 2-Bromopropane

The possibilities to apply personal ambient air monitoring by diffusive sampling and biological exposure monitoring by urinalysis for 2-bromopropane or its metabolites were explored. The abilities of carbon cloth to adsorb 2-bromopropane was examined by experimental vapor exposure followed by solvent extraction and FID-GC. Urine from factory workers and rats exposed to 2-bromopropane were analyzed for 2-bromopropane, acetone and isopropyl alcohol by FID-GC, and for bromide ion by ECD-GC after chemical methylation. Carbon cloth adsorbed 2-bromopropane in a manner linearly related to exposures up to 1500 mg/m³ and to 8 h. The adsorption could quantitatively detect a 15 min peak exposure at 3,000 mg/m³. In rat experiments, analyses of urine samples collected over a 4-h period after termination of a 4-h exposure to 2-bromopropane at 500, 1,000 or 1,500 mg/m³ showed that acetone and bromide ion were excreted dose-dependently. Essentially, no 2-bromopropane or isopropyl alcohol was detected. When the analytical methods were applied to urine samples from 5 male workers exposed to 2-bromopropane at a low level (3 mg/m³ as a geometric mean), acetone and bromide ion levels were within respective normal ranges in four cases, but were higher than the upper limits of the normal ranges in the fifth case of a foreman who probably had the highest exposure. Thus, diffusive sampling is applicable to monitor exposure to 2-bromopropane. Urinalysis for acetone and bromide ion in combination appears to be a promising selective tool for biological monitoring of occupational exposure to 2-bromopropane. Received: 26 February 1996/Revised: 29 May 1996     

Neurotoxicity of 2-bromopropane and 1-bromopropane, alternative solvents for chlorofluorocarbons

To clarify the neurotoxicity of 2-bromopropane (2-BP) in comparison with 1-bromopropane (1-BP), 36 Wistar strain male rats were divided into 4 groups of 9 and exposed daily to 100-ppm 2-BP, 1000-ppm 2-BP, 1000-ppm 1-BP, or fresh air for 8 h a day. Exposure to 1000 ppm of 1-BP was discontinued after 5 or 7 weeks' exposure because of the unexpected appearance of incomplete hindlimb paralysis followed by serious emaciation. The other groups were sacrificed at the end of 12 weeks' exposure. Exposure to 1000 ppm of 2-BP resulted in significant decreases in body weight and motor nerve conduction velocity (MCV) and elongation in distal latency (DL). A ball-like enlargement of myelin sheaths was observed. Significant reductions in the number of erythrocytes, platelets, and leukocytes, testicular germ cell loss, and seminiferous atrophy were also observed in this group, but not in 100-ppm 2-BP group. Exposure to 1000 ppm of 1-BP for 5 or 7 weeks caused a significant decrease in body weight and MCV and elongation in DL. Linearly arranged ovoid- or bubble-like debris of the axons and myelin sheaths in the teased tibial nerves and axonal swelling in gracilis nucleus were found in this group. No significant changes in hematological indices or histopathological findings of the testis were found in this group. In conclusion, 2-BP is neurotoxic to the peripheral nerves in addition to its toxic effects on the reproductive and hematopoietic systems at 1000 ppm. No noticeable changes were found in the rats exposed to 100 ppm of 2-BP. 1-BP is a potent neurotoxicant at 1000 ppm for 5 or 7 weeks, while testicular and hematopoietic toxicity was not found.     

A survey on exposure level, health status, and biomarkers in workers exposed to 1-bromopropane

BACKGROUND: The aim of this study was to evaluate the health effects of exposure mainly to 1-bromopropane, which is an alternative to ozone-depleting solvents, and to establish biomarkers for assessing 1-bromopropane exposure. METHODS: Twenty-four female and 13 male workers of a 1-bromopropane-factory were interviewed, and their urine and blood samples were collected. Measured parameters included 1-bromopropane levels in the factory, as well as individual exposure levels, urinary 1-bromopropane levels, enzymatic activity and M subunit's concentration of serum creatine kinase (CK). RESULTS: Frequent symptoms reported by workers exposed to 1-bromopropane were nose, throat, and eyes irritation or malaise and/or headache. Urinary 1-bromopropane levels correlated significantly with individual exposure levels, but enzymatic activity or CK-M subunit did not. CONCLUSIONS: The symptoms suggested irritation of the mucous membrane and possible adverse effects on the central nervous system. There were no severe chronic symptoms suggestive of neurological damage in workers exposed to less than 170 ppm. Urinary 1-bromopropane level may be a good indicator of exposure. Am. J. Ind. Med. 45:63-75, 2004.     

1-溴丙烷暴露对大鼠认知功能的影响

目的 观察1-溴丙烷(1-bromopropane,1-BP)对大鼠学习记忆功能及对胆碱能神经系统的影响.方法 雄性Wistar大鼠40只,随机分为4组:1-BP低剂量组(200mg/kg1-BP)、中剂量组(400mg/kg1-BP)、高剂量组(800mg/kg 1-BP)和对照组,每组10只.各组动物分别经灌胃给予相应受试物7 d后,采用Morris水迷宫定位航行试验和空间探索试验检测大鼠学习和记忆功能.水迷宫试验结束后次日断头处死大鼠,迅速剥离大鼠大脑和海马,冰浴中制备匀浆,取上清液,测定乙酰胆碱酯酶(AChE)、乙酰胆碱转移酶(ChAT)的活力.结果 定位航行试验中,1-BP染毒后,与对照组相比,中、高剂基组的逃避潜伏期、游泳路程明显延长,搜索效能降低,差异均有统计学意义(P＜0.05,P＜0.01).空间探索试验中,低、中、高剂量组穿越平台次数(分别为4.30±2.6、3.78±2.0、2.50±2.1)呈降低趋势,与对照组(7.20±2.8)比较,差异均有统计学意义(P＜0.05,P＜0.01),高剂量组的平台周边时间/总时间比值(0.55±0.14)明显低于对照组(0.76±0.15)和低剂量组(0.69±0.18),差异有统计学意义(P＜0.01).中、高剂量组大鼠大脑皮层AChE活力[分别为(1.246±0.423)、(1.397±0.503)U/mgpro]明显升高,与对照组[(0.918±0.276)U/mg pro]的差异有统计学意义(P＜0.05,P＜0.01),高剂量组海马组织中AChE活力[(0.583±0.118)U/mgpro]也明显高于对照组[(0.491±0.075)U/mgpro],差异有统计学意义(P＜0.05).1-BP染毒后,大脑皮层ChAT活力有降低趋势,但与对照组相比,差异无统计学意义(P＞0.05).结论 1-BP暴露能明显损伤大鼠学习记忆能力,可能与AChE活力升高相关.