Abnormalities in cadmium fluoride kinetics in serum, bile, and urine after single intravenous administration of toxic doses to rats

Cadmium fluoride (CdF2, CdF for short) is the most lethal and hepatotoxic of all Cd-containing compounds. The toxic effects of CdF appear to depend on its detoxification and elimination. This study was designed to determine the early dynamics of the absorption, systemic distribution, and metabolism of CdF. The kinetics of cadmium and fluoride were investigated in the blood, bile, and urine of rats as a model of accidental occupational exposure to CdF. The serum concentration-time profiles measured after intravenous CdF (1.34, 2.67 or 4.01 mg/ per kg body weight) administration were analyzed by compartmental modeling using the WinNonlin program. Bile and urine were collected for 300 min after the administration. The kinetic profiles indicate that the clearance of Cd was diminished in the 2.67 and 4.01 mg/kg groups, leading to a persistently high serum Cd level. The mean total biliary excretions of Cd in the 2.67 and 4.01 mg/kg groups were significantly higher than that in the 1.34 mg/kg group. The abnormal kinetics of Cd was attributable to severe hepatic injury that diminished the capacity for Cd accumulation. The elimination of serum F was delayed in the 4.01 mg/kg group. The mean urinary F excretion amount was not significantly higher in the 4.01 mg/kg group than in the 2.67 mg/kg group. The abnormal kinetics of F was attributable to nephrotoxicity that diminished its elimination from the kidney.     

Acute lethal toxicity, hyperkalemia associated with renal injury and hepatic damage after intravenous administration of cadmium nitrate in rats

Cadmium nitrate Cd(NO(3))(2) (CdN) is commonly used in Ni-Cd battery factories. The possibility of accidental exposure to CdN is great. CdN is very soluble in water compared to other Cd compounds. Therefore, acute toxicity would be expected to be quick due to rapid absorption after exposure. However, the mechanisms of CdN toxicity have not been fully elucidated. We investigated the acute lethal toxicity and harmful systemic effects of acute exposure to large doses of CdN. The lethal dose and dose-response study of the liver and kidney were determined after intravenous administration of CdN in rats. The LD(50) of CdN was determined to be 5.5 mg/kg. Doses of 2.1, 4.2, 6.3 mg/kg were selected for the dose-response study. Liver injury was induced at doses greater than 4.2 mg/kg. Severe hepatic injury occurred in the 6.3 mg/kg group, which would have been caused by acute exposure to the high concentration of Cd that exceeded the critical concentration in hepatic tissue. A remarkable decrease in urine volume in the 6.3 mg/kg group indicated acute renal failure. A decrease in creatinine clearance suggested acute glomerular dysfunction at doses greater than 4.2 mg/kg. Increases in urinary N-acetyl-beta-D-glucosaminidase/creatinine, beta(2)-microglobulin and glucose in the 6.3 mg/kg group indicated proximal tubular injury. Secretion of K ion was also severely affected by proximal tubular injury and severe decreases in urine volume, and an increase in serum K ion was identified at doses greater than 4.2 mg/kg. Thus severe hyperkalemia might be associated with the cardiac-derived lethal toxicity of CdN.     

Harmful effects and acute lethal toxicity of intravenous administration of low concentrations of hydrofluoric acid in rats

The acute toxicity of hydrofluoric acid (HFA) was investigated in a 24-h lethal dose study of intravenous infusion in rats. The lethal dose lowest (LDLo) and LD50 were 13.1 and 17.4 mg/kg, respectively. Harmful systemic effects were also studied 1 h after acute sublethal exposure to HFA. The maximum dose was set at 9.6 mg/kg (LD5). Rats were injected with HFA (1.6, 3.2, 6.4 or 9.6 mg/kg), saline, sodium fluoride (NaF) or HCl solution. NaF and HCl solution concentrations corresponded to the F- and H+ concentrations of 9.6 mg/kg HFA. Blood urea nitrogen (BUN) and Cr were significantly increased in response to HFA concentrations greater than 3.2mg/kg. Acute glomerular dysfunction also occurred at HFA concentrations greater than 3.2 mg/kg. HCO3- and base excess (BE) were significantly decreased in the 6.4 and 9.6 mg/kg groups. Ca2+ was significantly decreased, and K+ was increased in the 9.6 mg/kg group. BUN was significantly increased in the NaF and HFA groups and was increased in the HFA group compared with that in the NaF group. Cr was significantly increased in the HFA group only. HCO3- and BE were significantly decreased in the NaF and HFA groups and were increased in the HFA group compared with values in the NaF group. Ca2+ was significantly decreased in the NaF and HFA groups, and K+ was significantly increased in the NaF and HFA groups. F- exposure directly affected serum electrolytes. Mortality was thought to be due to cardiac arrhythmia resulting from hypocalcemia and hyperkalemia. Metabolic acidosis and renal failure were more severe in response to HFA exposure than in response to NaF exposure because of more free F-, which has strong cytotoxicity, in the HFA group than in the NaF group. Lethal effects of HFA are promoted by exposure routes such as inhalation that cause rapid absorption into the body. Even low exposure to HFA can cause acute renal dysfunction, electrolyte abnormalities and metabolic acidosis. These complications result in a poor prognosis.     

氟化钠对小鼠的急性毒性和致染色体突变作用研究

目的:研究氟化钠对小鼠的急性毒性及致染色体突变作用。方法:采用急性毒性试验和小鼠骨髓微核试验。设35.0 mg/kg、55.56 mg/kg8、8.18 mg/kg1、39.97 mg/kg2、22.18 mg/kg3、52.67 mg/kg5、59.79 mg/kg 7个剂量组NaF,观察氟化钠的急性毒性,计算经口半数致死量(LD50);另设高(34 mg/kg)、中(17 mg/kg)、低(8.5 mg/kg)3个剂量组NaF及环磷酰胺阳性对照组(50 mg/kg)、生理盐水空白对照组,观察小鼠骨髓细胞微核率的变化。结果:急性毒性实验各剂量组中毒小鼠均出现不同程度的抽搐、中枢神经系统先兴奋后抑制等表现,氟化钠经口LD50为168.34 mg/kg;氟化钠能诱变小鼠骨髓细胞微核率增高,中、高剂量组微核率均明显高于空白对照组(P<0.01),低剂量组微核率与空白对照组相比,差别无统计学意义(P>0.05)。结论:氟化钠属中等毒性,高浓度氟有致突变作用,能引起染色体损伤,具有潜在的遗传毒性效应。     

A comparison of the effects of single and repeated exposure to an organophosphate insecticide on acetylcholinesterase activity in mammals

Exposure to organophosphate (OP) pesticides can occur in free-living mammals in treated areas. Risk to nontarget animals from OPs usually is assessed with acute exposure data, but exposure of wild animals is likely to be intermittent and chronic. We compared the effects of single or repeated (hourly and daily) exposure to dimethoate on acetylcholinesterase (AChE) activity in laboratory mice to assess the suitability of standard laboratory tests for assessing risk. Mice were exposed either to a single dose (10 or 30 mg/kg) or to short-term repeated (three hourly doses of 10 mg/kg) intraperitoneal doses of dimethoate, and brain and serum AChE activity were measured. No significant difference was found in the degree of inhibition of AChE activity following acute and short-term repeated exposure. In a second experiment, mice were given three daily doses of 10 or 20 mg/kg of dimethoate, and both AChE activity and hepatic cytochrome P450 enzyme activity were measured. Daily exposure resulted in a dose-dependent decline in brain and serum AChE activity, and inhibition increased progressively with successively repeated exposures. However, this effect was relatively small compared to the effect of dose. Cytochrome P450 enzyme activity (CYP2B) was inhibited in the dimethoate-dosed mice. Our results indicate that acute dose-response toxicity studies are suitable models for predicting the likely occurrence of adverse effects from either short- or longer-term exposure of wild mammals to anticholinesterase compounds. Likely differences in exposure pattern between the laboratory and the natural environment are unlikely to bias the predictive power of these studies significantly.     

甲基汞急性暴露大鼠脑中汞蓄积及胆碱能神经递质改变的研究

目的 研究低剂量甲基汞短期暴露的神经毒性作用,为进一步探讨甲基汞早期神经毒性机制提供实验依据。方法 采用SD大鼠腹腔注射甲基汞,剂量分别为0．05、0．50及5．00mg／kg,并设对照组,分别暴露20min、1、4、24h时测定大鼠脑组织总汞含量、乙酰胆碱(ACh)含量及乙酰胆碱酯酶(AChE)活力。结果 除0．05mg／kg剂量组外,其余两组大鼠脑组织中汞含量在暴露20min就显著升高;0．05mg/kg组大鼠暴露4h后,脑汞含量也出现显著升高。各剂量组大鼠脑组织ACh及AChE都在暴露20min后就出现显著变化,并显示一定的剂量——效应和时间——效应关系。结论 甲基汞低剂量(0．05mg／kg)短时间暴露(20min)时脑组织ACh和AChE的改变表明此时可能启动了中枢神经系统某种调控机制。随暴露剂量和暴露时间增加,甲基汞蓄积于大鼠脑组织中,可引起脑组织ACh含量和AChE活力显著变化。     

轻稀土元素镧亚慢性暴露对大鼠钙、镁和铁代谢的影响

目的 探讨镧(lanthanum,La)亚慢性暴露对大鼠钙(Ca)、镁(Mg)和铁(Fe)代谢的影响.方法 将36只Wistar大鼠随机分为4组,每组9只,即对照组(0mg/kg)和三氯化镧(LaCl3)暴露组(0.1、2和40 mg/kg).分别以0.1、2和40 mg/kg的LaCl3给大鼠经口灌胃,每天1次,持续90 d,对照组则给予蒸馏水.暴露90 d后处死大鼠,取肝组织测定La、Ca、Mg和Fe水平;取血分离血清,测定Ca、P、Mg、Fe、总铁结合力(TIBC)、未饱和铁结合力(UIBC)水平.结果 与对照组(0 mg/kg)比较,各LaCl3暴露组(0.1、2和40 mg/kg)大鼠肝组织中La水平明显增高,差异均有统计学意义(均P＜0.001);中和高剂量组(2和40 mg/kg)大鼠肝组织中Ca水平明显降低,差异均有统计学意义(均P＜0.01);高剂量组(40 mg/kg)大鼠肝组织中Mg水平明显升高,差异有统计学意义(P＜0.01).与对照组(0 mg/kg)和40 mg/kg组比较,2mg/kg组大鼠血清Ca和Mg水平明显降低,差异有统计学意义(P＜0.05).高剂量组(40 mg/kg)大鼠血清UIBC水平明显高于对照组(0 mg/kg)和中剂量组(2 mg/kg),差异有统计学意义(P＜0.05).结论 中、高剂量(2和40 mg/kg)LaCl3亚慢性暴露对大鼠肝组织和血清中的Ca、Mg、Fe的水平和分布有一定的影响,这种变化可能是La生物学效应的机制之一.     

SAS probit analysis for cadmium mortality

In the quantitation of heavy metal effectiveness it is useful to compute the median lethal dose (LD₅₀) to the exposed population. The computerized Statistical Analysis System (SAS) of probit analysis is particularly useful in analyzing dose-response data because it is more accurate than the graphical methods currently in use and, in addition, provides fiducial limits with its estimates. Acute and chronic cadmium mortalities of young adult male and female Sprague-Dawley rats were determined by the SAS probit analysis. When male and female rats were administered comparable doses of cadmium chloride, based on individual body weights, males were more susceptible. A plausible explanation for this greater sensitivity of males to the heavy metal is testicular necrosis. The acute LD_{50 (30 days)} value for males was 5.99 mg Cd/kg body wt, with 95% fiducial limits of 4.71-7.54 mg Cd/kg body wt, as compared to 7.13 (5.18-8.85) mg Cd/kg body wt for females. When multiple (chronic doses of cadmium were injected, LD_{50 (30 days)} values were 4.25 (3.42-5.05) mg Cd/kg body wt and 5.14 (4.42-5.92) mg Cd/kg body wt for males and females, respectively. Values calculated 30 days after the last injection (at Day 60) were 3.38 (2.61-4.05) mg Cd/kg body wt and 4.65 (4.00–5.25) mg Cd/kg body wt for males and females, respectively. Chronic LD values indicate an increase in effectiveness of dose as time of injections was protracted.     

阿维菌素原药诱导大鼠肝组织热应激蛋白70基因表达的研究

目的研究阿维菌素原药诱导大鼠肝组织HSP70基因表达的变化,为阿维菌素原药环境污染早期监控及暴露人群的保护提供依据。方法将清洁级Wistar大鼠随机分成3个染毒组和1个对照组,每组12只,雌雄各半,3个染毒组每日经口灌胃不同浓度阿维菌素原药植物油稀释液,最终染毒剂量分别为2.5、1.25、0.625 mg/kg,连续染毒14 d,对照组给予等量花生油。观察大鼠一般状况,测定血清总蛋白(TP),并运用RT-PCR扩增技术观察肝组织HSP70 mRNA表达的变化。结果2.5 mg/kg剂量组雌性大鼠血清TP低于对照组(P<0.05);各染毒组动物肝组织HSP70 mRNA表达呈剂量-效应关系,2.5 mg/kg及1.25 mg/kg剂量组HSP70 mRNA表达明显增加(P<0.05)。结论阿维菌素原药能够敏感地诱导HSP70基因的表达,提示检测HSP70基因表达可作为阿维菌素原药早期监控的指标之一。     

饮水型SD大鼠氟斑牙模型的研制

目的建立饮水型大鼠氟斑牙模型,为深入研究氟性骨损伤发病机制提供科学依据。方法采用饮水加氟的方法复制大鼠氟斑牙模型,染氟剂量采用日测体重然后按体重(mg/kg)给予及尿氟、血氟监测的方法进行,尿氟、血氟采用微量氟法测定,血清中碱性磷酸酶(ALP)采用全自动生化分析仪测定,氟斑牙采用数码相机拍照,按照氟斑牙观测标准进行诊断及分度。结果 90 d末,高、中剂量组大鼠均出现明显氟斑牙,尿氟、血氟及血ALP含量与对照组相比均明显升高(P<0.05)。染氟剂量与尿氟水平显著相关(r=0.924,P=0.038);染氟剂量与血氟水平呈显著相关(r=0.948,P=0.026);高、中剂量组大鼠氟负荷水平明显高于对照组;氟斑牙发生率与染氟剂量呈正相关(r=0.983,P=0.017)。结论染氟剂量与氟斑牙的发生存在明显的剂量-反应关系:16 mg/kg和32 mg/kg的染氟剂量,14 d即可发生Ⅰ度氟斑牙,35 d即可发生典型氟斑牙。     

染氟大鼠血清中硬骨素表达水平及其在Wnt通路调控Runx2表达中作用的实验研究

目的观察染氟大鼠血清中硬骨素(SOST)、核心结合因子(Runx2)表达水平的变化,探讨SOST在经典Wnt通路调控Runx2表达中的作用。方法选取64只大鼠随机分为低剂量组(1.6mg/kgNaF)、中剂量组(16mg/kg NaF)、高剂量组(32mg/kg NaF)和对照组(0mg/kg NaF),每组16只,雌雄各半;采用微电极法进行尿氟、血氟测定;全自动生化分析仪测定血清中碱性磷酸酶(ALP)活力;ELISA试剂盒测定血清中SOST和Runx2。结果高剂量组在第35天时,SOST血清中浓度为(11.55±1.02)μg/L,表达开始下降;Runx2血清中浓度为(120.42±12.40)μg/L,表达开始升高;与对照组比较,差异有统计学意义(P<0.05)。第90天时,高、中剂量组SOST表达明显下降,Runx2表达明显升高,与对照组比较,差异均有统计学意义(P<0.01)。第90天时,大鼠体内SOST与Runx2表达水平呈负相关(r=-0.444,P<0.01)。结论高剂量的氟暴露可致大鼠体内SOST表达水平降低,Runx2表达水平升高;氟致骨损伤的发生可能与SOST的表达降低而对经典Wnt通路进行负调控,进而促进Runx2表达有关。     

Acute toxicity, histopathology, and coagulopathy in American kestrels (Falco sparverius) following administration of the rodenticide diphacinone

The acute oral toxicity of the anticoagulant rodenticide diphacinone was found to be over 20 times greater in American kestrels (Falco sparverius; median lethal dose 96.8 mg/kg body weight) compared with Northern bobwhite (Colinus virginianus) and mallards (Anas platyrhynchos). Modest evidence of internal bleeding was observed at necropsy, although histological examination of heart, liver, kidney, lung, intestine, and skeletal muscle revealed hemorrhage over a wide range of doses (35.1-675 mg/kg). Residue analysis suggests that the half-life of diphacinone in the liver of kestrels that survived was relatively short, with the majority of the dose cleared within 7 d of exposure. Several precise and sensitive clotting assays (prothrombin time, Russell's viper venom time, thrombin clotting time) were adapted for use in this species, and oral administration of diphacinone at 50 mg/kg increased prothrombin time and Russell's viper venom time at 48 and 96 h postdose compared with controls. Prolongation of in vitro clotting time reflects impaired coagulation complex activity, and generally corresponded with the onset of overt signs of toxicity and lethality. In view of the toxicity and risk evaluation data derived from American kestrels, the involvement of diphacinone in some raptor mortality events, and the paucity of threshold effects data following short-term dietary exposure for birds of prey, additional feeding trials with captive raptors are warranted to characterize more fully the risk of secondary poisoning.     

Lethal acute lung injury and hypoglycemia after subcutaneous administration of monochloroacetic acid

Hypoglycemia is suspected in the acute lethal toxicity induced by cutaneous exposure to monochloroacetic acid (MCA). Although it has been shown that hepato-renal dysfunction is involved, the mechanism and the target organs that directly affect mortality remain to be determined. We suspected respiratory failure as a main cause of death in some reported cases. We investigated dose-response effects, hypoglycemia, and lung injury in rats exposed to MCA. Serum glucose, blood gases, and parameters of alveolar injury in bronchoalveolar lavage fluid (BALF) were analysed 2 and 4 h after subcutaneous administration of MCA (108, 135 or 163 mg/kg). Apparent pulmonary injury and hypoglycemia were not identified 2 h after administration, but lactate dehydrogenase (LDH) and total cells in BALF were dose-dependently increased; and severe hypoglycemia was identified 4 h after administration. Blood gas analysis showed remarkable alveolar gas dysfunction as exchange in the 163 mg/kg group. Thus, hypoglycemia and lung injury appear to cause death in response to MCA exposure.     

Relative hepatotoxicity of some industrial solvents after intraperitoneal injection or inhalation exposure in rats

Intraperitoneal LD50 (lethal dose 50% kill) values and minimal liver toxic doses in female Sprague-Dawley rats were determined for the following industrial solvents: toluene, methylene chloride, carbon tetrachloride, 1,1,1-trichloroethane, 1,1,2-trichloroethane, trichloroethylene, ethanol, methyl ethyl ketone, and dioxane. For the following solvents LC50 values and minimal liver toxic air concentrations were also determined: xylene, styrene, chloroform, tetrachloroethylene, and dimethylformamide (DMF). The serum activity of the enzyme sorbitol dehydrogenase (SDH) was used as an indicator of liver damage. Carbon tetrachloride, chloroform, and DMF were hepatotoxic in low doses compared to LD50 values (TD50 (toxic dose 50%) values approximately 30, 90, and 50 mg/kg). Chloroform and DMF were hepatotoxic in comparatively low concentrations after a 4-hr inhalation exposure (TC50 (toxic concentration 50%) values approximately 590 and 740 mg/m3). Even relatively high doses of the other solvents did not raise the SDH activity. Significant direct (metabolite-mediated) hepatotoxicity seems to be an uncommon feature among commonly used industrial solvents.     

Perfluorooctanoic acid-induced immunomodulation in adult C57BL/6J or C57BL/6N female mice

BACKGROUND: Perfluorooctanoic acid (PFOA), an environmentally persistent compound of regulatory concern, has been reported to reduce antibody responses in mice at a single dose. OBJECTIVE: The aim of this study was to evaluate PFOA effects on humoral and cellular immunity using standard assays for assessing immune function, and to derive dose-response data. METHODS: C57BL/6J mice received 0 or 30 mg PFOA/kg/day for 10 days; half of the exposed groups were switched to vehicle and half continued on PFOA for five days. C57BL/6N mice received 0-30 mg/kg/day of PFOA in drinking water for 15 days. Mice were immunized with sheep red blood cells or sensitized to bovine serum albumin in Freund's complete adjuvant on day 10 of exposure; immune responses were determined 1 day post-exposure. RESULTS: We found that 30 mg PFOA/kg/day given for 10 or 15 days reduced IgM synthesis; serum collected 1 day postexposure contained 8.4 x 10(4) or 2.7 x 10(5) ng PFOA/mL, respectively. IgM synthesis was suppressed at exposures > or = 3.75 mg PFOA/kg/day in a dose-dependent manner, and IgG titers were elevated at 3.75 and 7.5 mg PFOA/kg/day. Serum PFOA at 3.75 mg/kg/day was 7.4 x 10(4) ng/mL 1 day postexposure, or 150-fold greater than the levels reported in individuals living near a PFOA production site. Using a second-degree polynomial model, we calculated a benchmark dose of 3 mg/kg/day, with a lower bound (95% confidence limit) of 1.75 mg/kg/day. Cell-mediated function was not affected. CONCLUSIONS: IgM antibodies were suppressed after PFOA exposure. The margin of exposure for reduced IgM antibody synthesis was approximately 150 for highly exposed human populations.     

菌核净对鲫鱼的雌激素效应研究

目的研究菌核净对鲫鱼的雌激素效应。方法每隔5d腹腔注射给予鲫鱼不同剂量菌核净（50mg/kg、100 mg/kg和200 mg/kg）诱导卵黄蛋白原（vitellogenin,VTG）的产生,同时设置阳性对照组17β-雌二醇（E2）和花生油对照组,2W后收集雄性鲫鱼血浆和肝脏进行VTG检测（ELISA法）,并测定血钙离子和血、肝总蛋白含量。结果100 mg/kg和200 mg/kg菌核净能诱导雄性鲫鱼血VTG产生,200 mg/kg菌核净能刺激雄性鲫鱼肝脏产生VTG,与阴性对照组相比,VTG含量均具有显著性差异;各剂量组菌核净对雄性鲫鱼血钙离子、血和肝总蛋白含量均无影响;但阳性对照E2能增高血钙离子水平,差异具有显著性。结论菌核净具有雌激素样作用。     

The acute toxicity and mutagenic potential of 3-methyl-2-benzothiazolinone hydrazone

3-Methyl-2-benzothiazolinone hydrazone (MBTH), widely used in analytical laboratories, was investigated for potential handling hazards. Tested as the hydrochloride, it was found to be of moderately high acute peroral toxicity with LD50 values in rabbits of 177 mg/kg (males) and 268 mg/kg (females), and in the rat 308 mg/kg (males) and 149 mg/kg (females). The major signs of toxicity, seen at peroral doses of 125 mg/kg and above, were convulsions. Although of low acute lethal percutaneous toxicity in rats (LD50 greater than 16 g/kg), rabbits were more sensitive with one of five males dying at an applied dose of 16 g/kg, and females having an LD50 of 12.3 g/kg; convulsions were seen in rabbits having applied cutaneous doses of 4 g/kg and above. There was no evidence for cutaneous inflammation after a 4 hour occluded contact with MBTH in rabbits, although following 24 hour occlusive contact in the acute percutaneous toxicity study there was erythema, edema, desquamation and, in a few animals, local necrosis. Ocular studies in rabbits indicated that, depending on the degree of contamination, MBTH produced mild to moderate eye irritation. In keeping with its low vapor pressure, there were no adverse effects from a 6 hour exposure of rats to an atmosphere saturated with any vapor produced from solid MBTH at ambient temperature. MBTH was positive in an Ames bacterial mutagenicity assay, particularly in the absence of metabolic activation. These studies indicate MBTH to be of moderately high acute peroral toxicity, of moderate percutaneous toxicity, a mild primary skin irritant, a mild to moderate eye irritant, and produced mutations in Salmonella. There is a need for skin and eye protection, and avoidance of swallowing, when handling MBTH.     

口服谷胱甘肽对氟所致大鼠脂质过氧化的影响

目的 探讨口服不同剂量的谷胱甘肽（GSH）对氟所致大鼠质过氧化的影响。方法 对事先饮用10天150mg/L氟化钠（NaF）的雄性Wistar大鼠分别给予60、300和600mg/kg GSH灌胃12周,同时设对照组（饮蒸馏 水）和单纯氟染毒组（150mg/LNaF ）,测定血清（全血）、肝、肾、心、睾丸和脑组织中超氧化物歧化酶（SOD） 活性和丙二醛（MDA）含量。结果 单纯氟染毒可使大鼠血清、肝、肾、脑MDA含量显著增加,全血、肝、肾、心、睾丸SOD活性显著降低;口服GSH后,血清、肝、肾、脑MDA的生成减少,肝、肾、心、睾丸和SOD活性显著上升,同是300mg/kgGSH可显著促进尿氟的排出。结论 氟可使大鼠脂质过氧化作用增强,抗氧化能力降低,口服GSH可拮抗氟致脂过氧化作用,增加抗氧化能力。     

总摄氟量与成人血清骨钙素的相关关系及其基准剂量

目的 探讨总摄氟量与血清骨钙素的剂量-效应关系及总摄氟量的基准剂量(benchmark dose,BMD),为氟骨症防治及总摄氟量标准的修订提供参考。方法 选择瓦庙村和新淮村为调查点,以家庭手压井饮水氟含量为依据,分别从瓦庙村和新淮村分层随机抽取103名和43名成年常住居民为被调查对象,调查内容包括家庭饮水和食物中氟含量,每日各种食物、饮水的摄入量,检测室内外空气中氟含量和血清骨钙素含量。计算每日总摄氟量,并根据每日总摄氟量将被调查对象分为四组:A组的总摄氟量为≤1.16 mg/(人·d)、B组>1.16 mg/(人·d)、C组>3.48 mg/(人·d)、D组>4.99 mg/(人·d),分别统计各组血清骨钙素含量及血清骨钙素的异常率。结果 瓦庙村居民的总摄氟量和血清骨钙素显著高于新淮村(P<0.01)。随着总摄氟量的增加,血清骨钙素含量逐渐增加,血清骨钙素的异常率也逐渐增加,总摄氟量与血清骨钙素及血清骨钙素异常率有显著的剂量-效应关系。依据血清骨钙素的异常率计算的总摄氟量的基准剂量和基准剂量下限(benchmark dose lower limitation,BMDL)分别为1.00 mg/(人·d)和0.67 mg/(人·d)。结论 骨钙素可能是氟接触人群骨损伤早期筛查的敏感指标;按照骨钙素计算的总摄氟量的BMDL显著低于国家总摄氟量标准。