Long-lasting neurotoxicity of prenatal benzene acute exposure in rats

Benzene is a common element of environmental pollution. Although this substance is not recognized as a teratogenic agent, it is not known whether prenatal exposure to benzene may induce neurobehavioral changes in the progeny. Benzene 0.1mg/kg was injected subcutaneously (s.c.) acutely at day 15 of gestation into pregnant female rats of the Sprague-Dawley strain and neurotoxicity of the substance was studied in pups and male adult animals of the same progeny. No change was found in total number of neonates, body weight and eye opening time between benzene-exposed animals and controls. No malformations were observed. At birth, neonatal reflexes (cliff aversion, forelimb placing, bar holding, forelimb grasping, startle) were scored in benzene-exposed pups and their percent appearance was found to be anticipated (more benzene-exposed pups exhibited reflexes each day) in comparison to that of control animals. Also, the completion (maximum appearance, i.e. 100% of the brood was found to exhibit each reflex) of neonatal reflexes in benzene-exposed animals preceded that of controls. Starting 2 months after birth, cognitive and motor performance was assessed only in male animals of the prenatally benzene-exposed progeny. The overall evaluation of motor activity in benzene-exposed animals in the open-field test revealed reduced ambulation in these rats as compared to control animals. Acquisition of active avoidance responses in the shuttle-box test, as assessed by the number of conditioned avoidance responses and the percent of learners, was impaired in benzene-exposed rats as compared to control animals. Prenatal exposure to benzene was also followed by reduced retention latency in a step-through passive avoidance task in two retention tests. These results suggest that acute exposure to benzene during gestational organogenesis may cause long-lasting changes in motor behavior and cognitive processes. This may be relevant for the assessment of benzene toxic profile for the progeny of pregnant subjects, although teratogenic effects are not observed.     

空气中正己烷、苯系物同时测定的热解吸气相色谱法

目的建立工作场所空气中正己烷、苯、甲苯、二甲苯同时测定的热解吸气相色谱方法。方法按照《车间空气监测检验方法研究规范》的要求进行实验室实验及现场实验。结果正己烷、苯、甲苯、二甲苯方法的平均相对标准偏差在4．9％以内,方法的最低检测浓度均在2．4mg/m^3以内,热解吸效率均在80％以上,空气中正己烷、苯、甲苯、二甲苯等在该方法条件下可同时分别测定。结论该方法各项指标均达到《车间空气监测检验方法研究规范》的要求,适用于工作场所空气中正己烷、苯、甲苯、二甲苯的同时监测。     

Reproductive history, occupational exposures, and thyroid cancer risk among women textile workers in Shanghai, China

Objectives: Thyroid cancer risk has been previously associated with increased age at first pregnancy and history of miscarriage. Occupational risk factors for thyroid cancer, with the exception of radioactive iodine, have not been well investigated. We conducted a case-cohort study nested in a cohort of 267,400 female textile workers in Shanghai, China, who had been followed for cancer incidence during 1989–1998. Methods: The analysis included 130 incident thyroid cases and 3,187 subcohort non-cases. Reproductive history was determined by questionnaire at baseline. Historical exposures were reconstructed from work history and information on factory processes and exposures. Cox proportional hazards analysis was performed to estimate hazard ratios (HR) for reproductive factors and occupational exposures. Results: Associations were observed between thyroid cancer and employment in jobs with 10 or more years of benzene exposure (HR 6.43, 95% CI: 1.08, 38) and formaldehyde exposure (HR 8.33, 95% CI: 1.16, 60). Administration workers also had an increased risk (HR 1.56, 95% CI: 1.08, 2.25). No associations between examined reproductive factors and thyroid cancer were observed in this study. Conclusions: Despite statistically imprecise risk estimates, the findings suggest potential associations with some occupational chemical exposures in this cohort of textile workers.     

Effect of in vivo exposure to benzene on the characteristics of bone marrow adherent cells

The effect of benzene on the adherent cell population, cultured from the bone marrow of exposed mice was investigated in the presence and absence of hydrocortisone. The adherent CFUs from exposed animals did not differ either in numbers or self-replicate ability to those derived from shown exposed animals. Adherent layers from mice exposed to 100 or 400 pp-benzene were devoid of fat cells regardless of the presence or absence of hydrocortisone. Hydrocortisone was shown to influence the proportion of acid phosphatase-positive cells derived from benzene-exposed animals. Those results suggest that benzene exposure may influence the bone marrow stromal cells.     

A simple analysis of 5 thinner components in human body fluids by headspace solid-phase microextraction (SPME)

A simple method for the extraction of 5 thinner components from human whole blood and urine, using the headspace solid-phase microextraction (SPME) method is presented. After heating a vial containing the samples with 5 compounds (toluene, benzene,n-butyl acetate,n-butanol andn-isoamyl acetate) at 80°C, a polydimethylsiloxane-coated SPME fiber was exposed to the headspace of the vial to allow adsorption of the compounds. The fiber needle was then injected into a capillary gas chromatography (GC) port. The headspace SPME-GC gave intense peaks for each compound and a low level of background noise was seen only for whole blood. Recovery rates o the 5 compounds by use of the headspace SPME-GC were 50–70%. Reproducibility for headspace SPME-GC data were excellent for both body fluids. The calibration curves showed linearity in the range 2–100 ng/0.5 ml whole blood or urine. The detection limits of each compound were 1.1–2.4 ng/0.5 ml sample. The present results on the analysis of 5 thinner components by headspace SPME-GC suggest its applicability to a number of other volatile compounds in forensic toxicology.     

The effect of occlusive and unocclusive exposure to xylene and benzene on skin irritation and molecular responses in hairless rats

Aromatic hydrocarbons readily penetrate the skin on dermal exposure, leading to irritation, inflammation and cytotoxicity. The effects of short-term occlusive and long-term unocclusive dermal exposure to benzene and xylene on the skin irritation response (transepidermal water loss (TEWL), skin moisture content and erythema) and cytokine/chemokine expression (interleukin-1 (IL-1), tumor necrosis factor- (TNF-) and monocyte chemoattractant protein-1 (MCP-1)) were investigated in hairless rats. Occlusive dermal exposure was carried out with 230 L of the chemicals for 1 h using Hill top chambers. In unocclusive dermal exposure, 15 L of the chemicals were applied to the skin every 2 h, for 8 h a day, for 4 days. The occlusive dermal exposure revealed a clear difference in the TEWL and erythema response of these chemicals (xylene>benzene) whereas unocclusive exposure revealed similar TEWL and erythema scores for both benzene and xylene. The expression of IL-1 was elevated 2.5- and 3.8-fold in response to occlusive and unocclusive exposure, respectively, vs control (P<0.01) for both the chemicals (benzene and xylene). Similarly, TNF- levels were elevated about 2.4- and 6.0-fold as a result of occlusive and unocclusive exposure, respectively, vs control (P<0.01). These results show that unocclusive exposure induced significantly higher TNF- expression than occlusive exposure (P<0.05). The MCP-1 expression in blood was slightly elevated compared with the control group, but this increase was not statistically significant (P>0.05). Similarly, MCP levels in skin were increased approximately 1.7- and 1.8-fold by occlusive and unocclusive exposure, respectively, compared with the control group (P<0.05). Our study demonstrates that the skin irritation profiles of benzene and xylene are similar and unocclusive long-term exposure to small amounts of these chemicals can induce more skin irritation and cytokine response than occlusive exposure.     

Metabolites of benzene are potent inhibitors of gap-junction intercellular communication

Chronic exposure to benzene has been shown to lead to bone marrow depression and the development of leukemia. The mechanism underlying the carcinogenicity of benzene is unknown, although a number of genetic changes including chromosomal aberrations have been associated with benzene toxicity. Metabolism of benzene is required for the induced toxicological effects. We have investigated the effect of trans,trans-muconaldehyde (MUC), hydroquinone (HQ), and four MUC metabolites on gap-junction intercellular communication (GJIC). Inhibition of GJIC has been considered a possible predictor of tumor promoters and non-genotoxic carcinogens, and shown to result in perturbation of hematopoiesis. MUC was found to be a strong inhibitor of GJIC (EC50=12 mol L^–1) in rat liver epithelial cells IAR20, with potency similar to that of chlordane (EC50=7 mol L^–1). HQ inhibited GJIC with an EC50 of 25 mol L^–1, and the metabolite OH/CHO with an EC50 of 58 mol L^–1. The other MUC metabolites tested, CHO/COOH and OH/COOH were weak inhibitors of GJIC whereas COOH/COOH had no effect. Benzene itself had no effect on GJIC when tested in concentrations up to 20 mmol L^–1. The relative potency observed for the metabolites on GJIC is similar to their hematotoxic effects. The effect of MUC on GJIC was observed to take place concordant with a dramatic loss of connexin 43 (Cx43) from the cells as visualized by Western blotting. Substances with the ability to inhibit Cx43-dependent GJIC have previously been observed to interfere with normal hematopoietic development. The ability of benzene metabolites to interfere with gap-junction functionality, and especially the dramatic loss of Cx43 induced by MUC, should therefore be considered as a possible mechanism for benzene-induced hematotoxicity and development of leukemia.     

苯对细胞增殖抑制率的影响及保护因素探讨

目的 探讨苯对骨髓单个核细胞增殖抑制率的影响,同时了解血清及氨磷汀能否作为保护因素减轻苯对细胞的影响.方法 实验分四组:空白对照组、(0.25、3.5、20μmol/L)苯组、(0.25、3.5、20μmol/L)苯+(2、10、50μg/mL)氨磷汀组、(0.25、3.5、20μmol/L)苯+血清组,通过细胞增殖检测(CCK-8法)并计算骨髓单个核细胞增殖抑制率.结果 高浓度苯组较低、中浓度苯组更能抑制细胞增殖(P＜0.01);(3.5、0.25μmol/L)苯+血清组细胞增殖抑制率均较相对应浓度的苯组减少(P＜0.05或P＜0.01);但20μmol/L苯+血清组与苯组间细胞增殖抑制率差异无统计学意义(P＞0.05).(0.25、3.5、20μmol/L)苯+(50、10、2μg/ml)氨磷汀,细胞增殖抑制率与相应浓度苯组比较,结果均具有显著性差异(P＜0.01或R＜0.05).结论 细胞增殖抑制率随苯剂浓度的增加而增加,苯毒性存在剂量依赖效应;血清及氨磷汀均能减轻苯对细胞的增殖毒性,可能可以作为苯中毒细胞的保护剂.     

间苯三酚联合米索前列醇在绝经后妇女取环中的应用

目的研究分析间苯三酚与米索前列醇联合用药在绝经后妇女取环患者的临床效果.方法选取我院于2011年3月至2012年3月收治的80例绝经后妇女取环患者的临床资料,将其按照随机分组的方式分为治疗组和对照组,治疗组42例患者采用药物联合治疗,即间苯三酚与米索前列醇治疗.对照组38例患者采用间苯三酚单独用药治疗,观察对比两组患者术中疼痛程度和宫颈松弛程度.结果两组患者术中疼痛程度,治疗组优于对照组,有统计学意义(P<0.05);两组患者宫颈松弛程度对比,治疗组软化有效率为97.62%,对照组软化有效率为78.95%,有统计学意义(P<0.05).结论绝经后妇女取环采用苯三酚与米索前列醇联合治疗,可以改善患者的临床症状且镇痛效果较好,安全有效,值得临床推广.     

常熟市皮件厂职业病危害状况调查

目的了解常熟市皮件厂苯、甲苯、二甲苯对工人健康状况的影响,为制定防治策略提供科学依据。方法采用现场调查及实验室检测相结合的方法,测定工作场所空气中苯、甲苯、二甲苯浓度,对苯接触组和对照组进行职业健康检查,检查外周血白细胞(WBC)、血红蛋白(Hb)、血小板(PLT)。结果 生产环境中个别作业点的苯和甲苯浓度超过国家卫生标准。职业健康检查中发现外周血WBC、Hb、PLT下降人数分别占23.3%、9.8%、5.5%。结论该市皮件厂作业工人血常规异常率较高,需要高度重视苯、甲苯、二甲苯对接触者的危害,加强职业卫生监督管理。