Cardiac arrhythmogenic action of benzo(a)pyrene in the rabbit

Rabbits treated with benzo(a)pyrene developed cardiac arrhythmias when exposed by inhalation to 8100 ppm trichloroethylene or 15000 ppm halothane to a greater extent and at lower doses of epinephrine challenge than did controls. Benzo(a)pyrene and 3-methylcholanthrene both increased the metabolism of trichloroethylene, but 3-methylcholanthrene did not increase its cardiotoxic effect. The basis of the arrythmogenic action of benzo(a)pyrene appears to be unrelated to its ability to induce xenobiotic metabolism.     

三氯乙烯诱发SD大鼠产生免疫反应的模型研究

目的研究SD大鼠对三氯乙烯(trichloroethylene,TCE)免疫刺激的反应,拟建立大鼠对TCE免疫反应的模型.方法背部皮内注射体积分数为15%的TCE免疫SD大鼠,1周1次,免疫5次后于大鼠左后足跖膜下注射TCE攻击,6h称左右后足重量计算肿胀度.取TCE免疫大鼠心脏血,分离并培养单个核细胞.将培养的细胞与系列浓度的TCE共同培养2d后,检测细胞酸性磷酸酶的活性,据此判断细胞的活化增殖程度.结果 TCE免疫大鼠攻击足肿胀度与空白对照组大鼠的相比差异显著(P＜0.005).体积分数为3%的TCE可使培养的大鼠血单个核细胞的增殖达到峰值.结论重复皮内注射TCE可使SD大鼠产生某种免疫反应.SD大鼠的单个核细胞可被TCE刺激活化.     

三氯乙烯染毒小鼠免疫功能变化研究

目的观察三氯乙烯对NIH小鼠染毒后免疫功能的变化.方法给予NIH小鼠皮下三氯乙烯染毒后研究胸腺、脾、肝脏等脏器系数变化情况、进行足跖肿胀实验、脾细胞转化实验等.结果三氯乙烯染毒小鼠胸腺、脾脏器系数未见明显变化.24h、48h时小鼠足跖肿胀系数明显高于溶剂对照组.80 mg/L三氯乙烯可抑制溶剂对照组脾淋巴细胞的增殖,但可促进三氟乙烯染毒组脾淋巴细胞增殖.结论三氯乙烯可能诱导NIH小鼠产生迟发性变态反应.     

Response to Comments by Caldwell et al. on Article “Applying Mode-of-Action and Pharmacokinetic Considerations in Contemporary Cancer Risk Assessments: An Example with Trichloroethylene”

have criticized our article in this journal (), in which we attempted to demonstrate how mode-of-action and pharmacokinetic considerations could be applied in a cancer risk assessment for trichloroethylene. This short response provides us the opportunity to endorse, without reservations, our earlier conclusions about a mode of action-based cancer risk assessment approach for trichloroethylene. Our comments here also note the continuing reluctance of regulators to embrace widely-held scientific consensus positions on mode of action rather than to maintain a regulatory bias requiring proof that no other mode-of-action could be operative—an impossible hurdle in any assessment. We remain concerned that policy and precautionary decisions rather than any true regard for the body of scientific research are likely to drive the US EPA risk assessment for TCE, and perhaps for most other animal carcinogens, despite research to clarify mode of action and tissue dosimetry considerations.     

Medico legal investigations into sudden sniffing deaths linked with trichloroethylene

Sudden deaths attributed to sniffing trichloroethylene are caused by the abuse of this solvent which produces pleasant inebriating effects with rapid dissipation. In the event of repeated cycles of inhalation, a dangerous and uncontrolled systemic accumulation of trichloroethylene may occur, followed by central nervous system depression, coma and lethal cardiorespiratory arrest.Sometimes death occurs outside the hospital environment, without medical intervention or witnesses and without specific necroscopic signs.Medico legal investigations into sudden sniffing deaths associated with trichloroethylene demand careful analysis of the death scene and related circumstances, a detailed understanding of the deceased's medical history and background of substance abuse and an accurate evaluation of all autopsy and laboratory data, with close cooperation between the judiciary, coroners and toxicologists.     

The trichloroethylene metabolite S-(1,2-dichlorovinyl)-l-cysteine but not trichloroacetate inhibits pathogen-stimulated TNF-α in human extraplacental membranes in vitro

Extraplacental membranes define the gestational compartment and provide a barrier to infectious microorganisms ascending the gravid female reproductive tract. We tested the hypothesis that bioactive metabolites of trichloroethylene (TCE) decrease pathogen-stimulated innate immune response of extraplacental membranes. Extraplacental membranes were cultured for 4, 8, and 24 h with the TCE metabolites trichloroacetate (TCA) or S-(1,2-dichlorovinyl)-l-cysteine (DCVC) in the absence or presence of lipoteichoic acid (LTA) or lipopolysaccharide (LPS) to simulate infection. In addition, membranes were cocultured with DCVC and Group B Streptococcus (GBS). DCVC (5–50 μM) significantly inhibited LTA-, LPS-, and GBS-stimulated cytokine release from tissue cultures as early as 4 h (P ≤ 0.05). In contrast, TCA (up to 500 μM) did not inhibit LTA-stimulated cytokine release from tissue punches. Because cytokines are important mediators for host response to infectious microorganisms these findings suggest that TCE exposure could potentially modify susceptibility to infection during pregnancy.     

甲醛和三氯乙烯联合染毒对小鼠行为功能的影响

目的研究甲醛和三氯乙烯联合染毒对小鼠神经行为的影响,为评价室内装修材料中甲醛和三氯乙烯对人体健康的危害提供科学依据。方法通过Morris水迷宫实验筛选健康清洁级昆明小鼠108只(雌雄各半),按照3×3析因的要求进行随机分组,采用静式吸入染毒,将小鼠暴露于不同浓度的甲醛、三氯乙烯及其二者的混合气体中,每天2 h,连续14 d。染毒结束后,采用Morris水迷宫实验和旷场实验对小鼠进行神经行为学测试。结果 Morris水迷宫实验结果显示,在定位导航实验中,单独及联合染毒组小鼠逃避潜伏期随着训练次数的增多均呈缩短趋势、且随着染毒剂量的增加小鼠逃避潜伏期延长,训练天数、甲醛和三氯乙烯对小鼠逃避潜伏期的影响差异均有统计学意义(P<0.01),同时甲醛和三氯乙烯对小鼠逃避潜伏期的影响存在交互作用(P<0.05)。在空间探索实验中,甲醛和三氯乙烯单独及联合染毒均可致小鼠第一次跨越原平台位置的时间延长。二者联合染毒对小鼠第一次跨越原平台位置的时间和原平台象限游泳距离占总距离百分比的影响存在交互作用(P<0.05),且表现为协同。旷场实验结果显示,甲醛和三氯乙烯染毒致小鼠在中央区活动时间延长,站立次数下降,中央区活动距离占总距离百分比增大,二者对小鼠在旷场实验中的中央区活动时间、直立次数以及中央区活动距离占总距离百分比的影响均有交互作用(P<0.01),且表现为协同。结论甲醛和三氯乙烯能降低小鼠的学习记忆能力,影响神经行为表现,二者联合染毒具有一定的协同作用。     

Modulation of trichloroethylene in vitro metabolism by different drugs in human

Toxicological interactions with drugs have the potential to modulate the toxicity of trichloroethylene (TCE). Our objective is to identify metabolic interactions between TCE and 14 widely used drugs in human suspended hepatocytes and characterize the strongest using microsomal assays. Changes in concentrations of TCE and its metabolites were measured by headspace GC–MS. Results with hepatocytes show that amoxicillin, cimetidine, ibuprofen, mefenamic acid and ranitidine caused no significant interactions. Naproxen and salicylic acid showed to increase both TCE metabolites levels, whereas acetaminophen, carbamazepine and erythromycin rather decreased them. Finally, diclofenac, gliclazide, sulphasalazine and valproic acid had an impact on the levels of only one metabolite. Among the 14 tested drugs, 5 presented the most potent interactions and were selected for confirmation with microsomes, namely naproxen, salicylic acid, acetaminophen, carbamazepine and valproic acid. Characterization in human microsomes confirmed interaction with naproxen by competitively inhibiting trichloroethanol (TCOH) glucuronidation (K_i = 2.329 mM). Inhibition of TCOH formation was also confirmed for carbamazepine (partial non-competitive with K_i = 70 μM). Interactions with human microsomes were not observed with salicylic acid and acetaminophen, similar to prior results in rat material. For valproic acid, interactions with microsomes were observed in rat but not in human. Inhibition patterns were shown to be similar in human and rat hepatocytes, but some differences in mechanisms were noted in microsomal material between species. Next research efforts will focus on determining the adequacy between in vitro observations and the in vivo situation.     

新型等离子体与光催化复合空气净化技术研究

目的 研究一种新型的等离子体-光催化复合空气净化技术.方法 采用三氯乙烯气体作为空气污染物对等离子体单元和光催化单元进行复合试验,选择等离子体加光催化或光催化加等离子体两种复合方式、改变两者之间的距离以及在其间放置网状物,检测其对三氯乙烯的净化效率.结果 等离子体加光催化复合方式具有明显协同效应,而且在两者的单独净化效率较低时更明显;两者间距在32.5 cm时净化效率可以达到90%以上;放置网状物对其净化效率都具有影响,放置不锈钢网时降解率为76.3%,放置无纺布时降解率为79.2%.结论 采用等离子体加光催化的复合方式、保持合适的间距,并放置适当材料的网,具有较显著的协同促进效应,可提高净化技术的复合效应.     

Trichloroethylene: Mechanistic,epidemiologic and other supporting evidence of carcinogenic hazard

The chlorinated solvent trichloroethylene (TCE) is a ubiquitous environmental pollutant. The carcinogenic hazard of TCE was the subject of a 2012 evaluation by a Working Group of the International Agency for Research on Cancer (IARC). Information on exposures, relevant data from epidemiologic studies, bioassays in experimental animals, and toxicity and mechanism of action studies was used to conclude that TCE is carcinogenic to humans (Group 1). This article summarizes the key evidence forming the scientific bases for the IARC classification. Exposure to TCE from environmental sources (including hazardous waste sites and contaminated water) is common throughout the world. While workplace use of TCE has been declining, occupational exposures remain of concern, especially in developing countries. The strongest human evidence is from studies of occupational TCE exposure and kidney cancer. Positive, although less consistent, associations were reported for liver cancer and non-Hodgkin lymphoma. TCE is carcinogenic at multiple sites in multiple species and strains of experimental animals. The mechanistic evidence includes extensive data on the toxicokinetics and genotoxicity of TCE and its metabolites. Together, available evidence provided a cohesive database supporting the human cancer hazard of TCE, particularly in the kidney. For other target sites of carcinogenicity, mechanistic and other data were found to be more limited. Important sources of susceptibility to TCE toxicity and carcinogenicity were also reviewed by the Working Group. In all, consideration of the multiple evidence streams presented herein informed the IARC conclusions regarding the carcinogenicity of TCE.