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.     

慢性砷染毒对大鼠附睾上皮细胞凋亡的影响

目的探讨慢性砷染毒对大鼠附睾上皮细胞凋亡的影响。方法将40只健康清洁雄性SD大鼠随机分为4组,分别为对照(蒸馏水)组和2.4、12.0、60.0 mg/L亚砷酸钠染毒组,每组10只。采用自由饮用方式进行连续染毒6个月。采用TUNEL细胞凋亡染色法测定大鼠附睾上皮凋亡细胞的凋亡情况,采用Western blot法测定附睾组织内caspase-3、caspase-9蛋白的表达水平,并测定精子顶体完整率和精子畸形率。结果与对照组比较,各浓度砷染毒组大鼠附睾管的细胞凋亡率较高,差异均有统计学意义(P0.05);且随着砷染毒浓度的升高,大鼠附睾管的细胞凋亡程度加重。与对照组比较,各浓度砷染毒组大鼠附睾内caspase-3、caspase-9蛋白表达水平均较高,差异有统计学意义(P0.05);且随着砷染毒浓度的升高,大鼠附睾内caspase-3、caspase-9蛋白的表达水平呈上升趋势。与对照组比较,12.0、60.0 mg/L砷染毒组大鼠精子顶体完整率均较低,而精子畸形率均较高,差异均有统计学意义(P0.05);且随着砷染毒浓度的升高,大鼠精子顶体完整率呈下降趋势,而精子畸形率呈上升趋势。结论慢性砷染毒通过激活caspase-3或caspase-9等途径实现大鼠附睾组织的损伤及凋亡。     

DEHP亚慢性暴露对大鼠精子运动参数影响

目的观察邻苯二甲酸(2-乙基已基)酯(DEHP)染毒90 d对大鼠精子运动能力的毒性作用。方法将健康清洁级SD雄性大鼠40只随机分为对照组和3个DEHP染毒组(5、50、500 mg/kg),进行90 d经口染毒;取睾丸、附睾称重,并用扩散法收集大鼠附睾尾精子,应用计算机辅助精子分析系统(CASA)对精子的运动参数进行检测。结果 5 mg/kg DEHP组大鼠精子直线性(LIN)为(44.00±2.52)%,明显低于对照组(50.00±2.71)%(P0.05);500 mg/kg DEHP组大鼠精子鞭打频率(BCF)为(5.8±4.2)Hz,明显低于对照组(10.4±1.7)Hz(P0.05);与对照组比较,500 mg/kg DEHP组大鼠精子的平均路径速度(VAP)、直线运动速度(VSL)、曲线运动速度(VCL)、精子头侧摆幅度(ALH)、BCF明显下降,差异均有统计学意义(均P0.05);随着DEHP染毒浓度增加,大鼠精子各项运动参数逐渐降低,精子的运动能力下降。结论 DEHP对大鼠附睾精子的运动能力有直接毒性作用。     

锰对大鼠生精细胞凋亡及caspase-3表达的影响

[目的]研究染锰大鼠睾丸生精细胞凋亡和caspase-3表达的变化。[方法]雄性SD大鼠48只随机分为6组:空白对照组,15mg/kg、30mg/kgMnCl2组。8只/组。15mg/kg、30mg/kgMnCl2组分别染锰(MnCl2·4H2O)4周和6周,空白对照组给予等容生理盐水(NS),给锰及生理盐水途径均为腹腔注射,5d/周,1次/d,大鼠分别于第4周末和第6周末处死,取睾丸和附睾作以下检测:①检测精子数量;②应用末端脱氧核糖核酸转移酶介导的dUTP切口末端标记技术(terminal deoxynucleotidy transferase mediated dUTP nick end labeling,TUNEL)检测睾丸生精细胞凋亡指数(apoptosis index,AI);③免疫组组织化学链酶亲和素-生物素-过氧化物酶复合物(streptavidin-biotin-peroxidase complex,SABC)法检测生精细胞caspase-3表达。[结果]①与空白对照组比较,各染锰组精子数量均显著降低(P﹤0.05),生精细胞AI均升高(P﹤0.05),caspase-3阳性细胞率均显著升高(P﹤0.05)。②染锰剂量相同,染锰6周组与染锰4周组比较,精子数量均显著降低,生精细胞AI与caspase-3阳性细胞率均显著升高(P﹤0.05)。③染锰时间相同,30mg/kgMnCl2组与15mg/kgMnCl2组比较,精子数量均显著降低(P﹤0.05),生精细胞AI和caspase-3阳性细胞率均显著升高(P﹤0.05)。④各组大鼠精子数量和生精细胞AI呈负相关(r=-0.700,P﹤0.05),和生精细胞caspase-3阳性细胞率呈负相关(r=-0.870,P﹤0.05),生精细胞AI和caspase-3阳性细胞率呈正相关(r=0.855,P﹤0.05)。[结论]过量锰诱发大鼠生精细胞caspase-3高表达,从而导致凋亡增加,精子数量减少,这可能是大鼠生精障碍的主要机制。     

2,4-D异辛酯对大鼠精子的影响及与热休克蛋白70的表达关系

目的　探讨 2 ,4 D异辛酯亚慢性染毒对大鼠附睾尾精子的影响及与睾丸组织热休克蛋白 70 (HSP70 )表达之间的关系。方法　健康成年大鼠 96只 ,随机分为 4组 ,雌雄各半 ,分别以每天6 0 .0、6 .0、0 .6mg kg的剂量染毒 3个月 ,对照组给予等量色拉油 ,用Westernblot方法测定大鼠睾丸组织HSP70水平 ,并检测附睾尾精子的变化。结果　各剂量组HSP70表达水平均明显高于对照组 ,低剂量组表达最明显 ,高、中剂量组次之。高剂量组附睾尾精子总数 (12 6 .4 4± 2 1.0 1)减少 ,与对照组(16 2 .5 2± 2 1.91)比较 ,差异有显著性 (P <0 .0 5 ) ;各剂量组精子存活率均比对照组低 ,仅高剂量组(6 .2 4 %± 1.15 % )与对照组 (19.0 1%± 11.82 % )的差异有显著性 (P <0 .0 1) ,各剂量组精子畸形率均比对照组高 ,但差异无显著性 (P >0 .0 5 )。结论　高剂量 2 ,4 D异辛酯亚慢性染毒对雄性大鼠生殖有明显影响 ,各剂量组睾丸组织HSP70水平均高于对照组 ,说明HSP70在抵抗 2 ,4 D异辛酯毒性和维护精子的正常形成中可能起到一定作用。     

维生素A缺乏对大鼠生精能力及睾丸标志酶活性的影响

目的　探讨维生素A缺乏对大鼠生精能力及睾丸标志酶活性的影响。方法　采用断乳期 2 1～ 2 3天Wistar雄性大鼠 ,体重 35～ 4 5g ,随机分为正常组 ,VA 缺乏组 ,分别饲喂正常饲料及无VA 的饲料 ,喂养 90天后 ,称重 ,乌拉坦麻醉 ,腹主动脉取血 ,采用荧光法测定血清VA 含量 ;摘取双侧睾丸和附睾。计算睾丸和附睾脏器系数 ,作精子相对计数及精子畸形率检测 ,测定睾丸中乳酸脱氢酶 (LDH)、碱性磷酸酶 (ALP)及γ -谷氨酰转肽酶 (GGT)活性 ,测定睾丸中总胆固醇 (CHOL)含量。结果　维生素A缺乏组雄鼠血清VA 含量明显低于正常组雄鼠 (t =4 1 5 1,P <0 0 1) ,睾丸、附睾的脏器系数下降 (t=12 12 ,3 83,P <0 0 1) ,精子数明显减少 (P <0 0 1) ,精子畸形率明显增高 (P <0 0 1)。睾丸中乳酸脱氢酶 (LDH)及γ -谷氨酶转肽酶 (GGT)活性明显降低 (t=3 2 2 ,3 0 7,P <0 0 1) ,碱性磷酸酶 (ALP)活性明显降低 (t′=2 83,P <0 0 5 ) ,睾丸中总胆固醇 (CHOL)含量明显降低 (t=3 37,P <0 0 1)。结论　维生素A缺乏影响雄性大鼠的生精能力、睾丸标志酶的活性及其胆固醇的含量     

牛磺酸对青春前期大鼠睾丸缺血再灌注损伤的保护作用

目的探究牛磺酸注射液对青春前期大鼠睾丸扭转复位后缺血再灌注损伤的保护作用。方法将32只4w龄健康雄性SD大鼠,随机分为假手术组、生理盐水组、牛磺酸单次应用组和牛磺酸连续应用组,每组8只,建立左侧睾丸扭转复位动物模型(720°,2h)。于术后6 w处死大鼠,取左侧睾丸及附睾,计算睾丸系数和测定活动精子的百分率、精子活动率和精子计数,检测睾丸组织中总抗氧化能力(T-AOC)、超氧化物歧化酶(SOD)活性、一氧化氮合酶(NOS)活性、丙二醛(MDA)含量。常规制备病理切片,光镜下观察睾丸组织病理学改变。结果与生理盐水组相比,两应用组的睾丸系数、活动精子的百分率、精子活动率、精子计数、SOD、T-AOC、NOS活性均增加,MDA含量均降低(P0.05);与单次应用组相比,连续应用组和假手术组睾丸系数、精子的百分率、精子活动率、精子计数、SOD、T-AOC活性均增加(P0.05);与连续应用组相比,假手术组睾丸系数、精子活动率、精子计数增加(P0.05)。生理盐水组可见生精小管退变,间质出现水肿,两应用组使睾丸扭转复位诱发的组织学改变明显改善。结论牛磺酸注射液可以通过保护抗氧化酶活性和抑制脂质过氧化,提高精子活动率和精子计数,对青春前期大鼠睾丸缺血再灌注损伤有明显的保护作用,且连续应用明显优于单次应用。     

铁皮石斛花对亲代及子代大鼠睾丸组织和精子质量的影响

目的研究铁皮石斛花对亲代及子代雄性大鼠睾丸、附睾和精子数量、质量的影响,为评价铁皮石斛花安全性提供依据。方法设低、中、高3个剂量组和对照组,每组10只SD雄性大鼠,各剂量组以喂饲方式给予含2.0、4.0、6.4 g/kgbw铁皮石斛花的基础饲料。喂饲3个月后测定亲代(P)及子一代(F1)和子二代(F2)大鼠体重、睾丸、附睾脏器重并计算脏体比;显微镜下观察精子数量、活动率和畸形率;采用苏木精-伊红染色法观察睾丸、附睾组织的组织学形态。结果各组P、F1和F2雄性大鼠体重、睾丸重、睾丸体比、附睾重、附睾体比、精子数量和精子活动率比较,差异均无统计学意义(P0.05)。高剂量组P、F1、F2雄性大鼠精子畸形率比较,差异均无统计学意义(P0.05)。P、F1和F2雄性大鼠睾丸和附睾组织形态均无明显的改变。结论铁皮石斛花对亲代及子代雄性大鼠睾丸组织和精子数量、质量均未见明显不良影响。     

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.     

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。     

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.     

Cerebral excitability in pup rats prenatally exposed to 1-bromopropane is suppressed by bromide accumulated in the brain

Previously, we reported that prenatal exposure to 1-bromopropane (1-BP) causes the accumulation of bromide (Br^-) in the brain of rat pups. Here, we aimed to investigate the effects of Br^- accumulation in rat pups prenatally exposed to 1-BP vapor. Dam rats were exposed to 1-BP (400 or 700 ppm; 1-BP group) by inhalation, or to NaBr (20 mM; Br^- group) in drinking water during gestation days 1–20. We also analyzed pentylenetetrazole (PTZ, 60 mg/kg, ip)-induced behavioral changes in pups prenatally exposed to 1-BP or Br^- on postnatal day (PND) 14. PTZ-induced epileptic convulsions were inhibited in both 1-BP (700 ppm) and Br^- groups. The inhibition of neuronal excitability induced by Br^- was evaluated electrophysiologically using the hippocampal slices obtained from PND14–16 pups. PTZ (2 mM) failed to induce epileptiform discharge in the presence of 1.2 mM Br^- in the slices obtained from the control group. However, it induced epileptiform discharge following the removal of Br^-, by perfusing artificial cerebrospinal fluid into the slices obtained from the Br^- group. Our results indicate that Br^- accumulates in the brain of neonatal rat pups prenatally exposed to 1-BP vapor suppressed neuronal excitability.     

Neurologic abnormalities in workers of a 1-bromopropane factory

We reported recently that 1-bromopropane (1-BP; n-propylbromide, CAS Registry no. 106-94-5), an alternative to ozone-depleting solvents, is neurotoxic and exhibits reproductive toxicity in rats. The four most recent case reports suggested possible neurotoxicity of 1-BP in workers. The aim of the present study was to establish the neurologic effects of 1-BP in workers and examine the relationship with exposure levels. We surveyed 27 female workers in a 1-BP production factory and compared 23 of them with 23 age-matched workers in a beer factory as controls. The workers were interviewed and examined by neurologic, electrophysiologic, hematologic, biochemical, neurobehavioral, and postural sway tests. 1-BP exposure levels were estimated with passive samplers. Tests with a tuning fork showed diminished vibration sensation of the foot in 15 workers exposed to 1-BP but in none of the controls. 1-BP factory workers showed significantly longer distal latency in the tibial nerve than did the controls but no significant changes in motor nerve conduction velocity. Workers also displayed lower values in sensory nerve conduction velocity in the sural nerve, backward recalled digits, Benton visual memory test scores, pursuit aiming test scores, and five items of the Profile of Mood States (POMS) test (tension, depression, anxiety, fatigue, and confusion) compared with controls matched for age and education. Workers hired after May 1999, who were exposed to 1-BP only (workers hired before 1999 could have also been exposed to 2-BP), showed similar changes in vibration sense, distal latency, Benton test scores, and depression and fatigue in the POMS test. Time-weighted average exposure levels in the workers were 0.34-49.19 ppm. Exposure to 1-BP could adversely affect peripheral nerves or/and the central nervous system.     

1-溴丙烷对两种雄性大鼠肝脏毒性的研究

目的研究1-溴丙烷对两种雄性大鼠的肝脏毒性及谷胱甘肽S-转移酶(GST)在肝脏解毒代谢中的作用。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。通过血浆的生化指标和病理切片对肝脏的功能和形态进行了评价。利用化学比色法和实时定量PCR法对肝脏中的GST的活力和基因表达水平进行测量。结果1-溴丙烷暴露可引起两种大鼠体重的下降及肝脏重量的上升;病理发现肝脏中央静脉周围的肝细胞出现空泡样改变,血浆中CK、ALT和TBIL和DBIL等指标上升明显;两种大鼠肝脏细胞胞浆的GST活力增强,Fischer344大鼠微粒体GST的活力也增强;肝脏组织的GSTmRNA表达水平升高。结论1-溴丙烷暴露对两种雄性大鼠具有肝脏毒性,GST在1-溴丙烷的肝脏解毒代谢中可能起到较重要作用。     

低浓度1-溴丙烷对接触者神经系统的影响

[目的]观察低浓度1-溴丙烷(1-BP)接触对人外周神经系统和中枢神经系统功能的影响。[方法]以25名1-BP接触工人为接触组(其中男性17人)和25名非接触工人为对照组(其中男性17人),使用问卷调查收集研究对象的年龄、性别和吸烟、饮酒状况及教育程度等信息,测定1-BP接触的时间加权平均浓度(TWA),进行神经传导速度和神经行为学检查。[结果]接触组女性和暴露组女性相比,一般情况中除年龄(接触组女性年龄低于对照组,P<0．05)外,其他方面差别均无显著性;接触组男性和暴露组男性一般情况差别均无显著性。1-BP接触浓度的TWA平均值80．4(2．0-384．9)mg/m3;男性接触组与其对照组相比,运动神经传导速度减慢,末端潜伏期延长,简明情绪量表(profile of mood states,PMOS)表中紧张焦虑项得分增高,视觉记忆项得分降低,差异有显著性(P<0．05);女性接触组与其对照组各项比较差别均未见统计学意义(P>0．05)。[结论]低浓度1-BP暴露能对男性接触者外周神经传导速度和神经行为产生影响。     

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.     

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.