Computer assisted recognition and quantitation of the effects of airborne chemicals acting at different areas of the respiratory tract in mice

The pattern and timing of a normal breath in unanesthetized mice was analyzed from measurement of inspiratory and expiratory airflows (V^.I and V^.E). Airflow was measured via a differential pressure transducer, attached to a pneumotachograph, which itself was attached to a body plethysmograph into which a mouse was placed. The analog voltage from the differential pressure transducer was digitized and stored for analysis on a microcomputer. Criteria were developed to classify each breath as normal (N) or belonging into one of seven abnormal categories. The abnormal categories were arrived at by computer analysis, recognizing specific modifications of the normal pattern into patterns of: sensory irritation of the upper respiratory tract (S), airflow limitation within the conducting airways of the lungs (A) or pulmonary irritation at the alveolar level (P). Combinations of these effects, i.e., S+A, P+A, P+S and P+S+A were also recognized. Computer analysis of each breath also permitted quantitative evaluation of the degree of S, A or P abnormalities. To induce each type of effect we used inhalation exposures to 2-chlorobenzylchloride, carbamylcholine or propranolol. We propose that this approach will permit rapid evaluation of the possible effects of airborne chemicals at three levels of the respiratory tract, with the classification of the type of effect easily obtained in an objective way using well defined criteria, followed by quantitation of the degree of each effect. Received: 16 December 1993 / Accepted: 11 April 1994     

Exposure to Bisphenol A prenatally or in adulthood promotes T(H)2 cytokine production associated with reduction of CD4CD25 regulatory T cells

BACKGROUND: Bisphenol A (BPA) is a widespread endocrine-disrupting chemical that can affect humans and animals. OBJECTIVES: We investigated the effects of adult or prenatal exposure to BPA on T-helper (T(H))1/T(H)2 immune responses and the mechanisms underlying these effects. METHODS: To evaluate the effects of exposure to BPA in adulthood, male Leishmania major-susceptible BALB/c and -resistant C57BL/6 mice were subcutaneously injected with 0.625, 1.25, 2.5, and 5 mumol BPA 1 week before being infected with L. major. To evaluate prenatal exposure, female mice were given BPA-containing drinking water at concentrations of 1, 10, and 100 nM for 2 weeks, then mated, and given BPA for another week. Male 10-week-old offspring were infected with L. major. Footpad swelling was assessed as a measure of the course of infection. RESULTS: Mice exposed to BPA prenatally or in adulthood showed a dose-dependent increase in footpad swelling after being infected with L. major. Exposure to BPA in adulthood significantly promoted antigen-stimulated production of interleukin (IL)-4, IL-10, and IL-13 but not interferon-gamma (IFN-gamma). However, mice prenatally exposed to BPA showed increased production of not only IL-4 but also IFN-gamma. The percentages of CD4(+)CD25(+) cells were decreased in mice exposed to BPA either prenatally or in adulthood. Effects of prenatal BPA exposure were far more pronounced than effects of exposure in adulthood. CONCLUSION: BPA promotes the development of T(H)2 cells in adulthood and both T(H)1 and T(H)2 cells in prenatal stages by reducing the number of regulatory T cells.     

某市自来水与原水中环境内分泌干扰物的调查

目的了解某市自来水以及原水中环境内分泌干扰物(endocrine disruptingchemicals,EDCs)污染的现状。方法于2006年4月至2007年2月,采集某市的自来水源水以及末梢水样品15件,每件20 L。水样经XAD-4树脂吸附处理后,用丙酮-二氯甲烷洗脱。洗脱液经浓缩后,采用气相色谱-质谱(GC-MS)联机检测。结果3个水厂的15件水样中共检测出78种有机污染物,主要包括邻苯二甲酸酯类、酚类、苯系物和烷烃类等。所有水样中均检出酞酸酯类化合物,其中双(2-乙基己基)邻苯二甲酸酯、邻苯二甲酸二丁酯和五氯酚为可疑EDCs,其浓度范围分别为0.004 75～4.50μg/L、0.002 25～2.39μg/L和0.727μg/L。结论该市的自来水原水和末梢水中存在较多的有机污染物,其中主要的EDCs为酞酸酯类和酚类化合物。该市饮用水中EDCs污染的变化趋势和健康效应需引起进一步关注。     

《有毒作业分级（GB12331-90）》修订的思考

国家技术监督局1990年4月颁布、1991年1月实施的中华人民共和国国家标准《有毒作业分级》（GB12331-90）（以下简称‘《分级》）是我国工作场所职业卫生管理的重要依据。《分级》是基于毒理学研究资料，在总结建国以来劳动安全工作的经验基础上制定的。有毒作业危害分级的三个基本要素是毒物危害程度级别、工人劳动时间和作业环境中毒物浓度超标倍数，是针对有毒有害作业环境进行的分级，最终目标是为了保护作业人员健康。     

The pathogenesis of inflammatory disease: Surgical shock and multiple system organ failure

Chronic inflammatory disease, embracing rheumatoid arthritis (RA), inflammatory bowel disease (IBD), hepatitis, asthma, atherosclerosis, multiple system organ failure (MSOF), etc., is mediated by reactive oxygen species (ROS). These ROS originate from activated neutrophils in infections and in immune and autoimmune reactions, from tissue deposits of ferritin, and from futile cycling of cytochrome P450 (CYP) following exposure to persistent chemicals, and may be perpetuated by the actions of complement, cytokines and eicosanoids. Acute inflammation is normally arrested by removal of ROS by tissue glutathione (GSH) and the antioxidant vitamins, A, C and E, all of which are regenerated by NADH and NADPH. Failure of this antioxidant defence system can lead to oxidative stress and to chronic inflammatory disease, including surgical shock and MSOF. The roles of oxidative stress and microcirculatory arrest in promoting MSOF, and of GSH, the antioxidant defence system, and fibronectin in preventing this, are reviewed in the light of recent experimental studies of surgical shock, including fasting, anaesthesia, hepatic ischaemia and reperfusion.     

Safety evaluation of the mixture of chemicals at a specific workplace: theoretical considerations and a suggested two-step procedure

Procedures for the selection of compounds with high health hazard potential are reviewed, and major aspects of the assessment of health risks associated with exposure to mixtures of chemicals are discussed. Examples are given of additivity and synergism of effects following exposure to mixtures. Using these data from the literature a two-step procedure for the safety evaluation of the mixture of chemicals occurring at a specific workplace is suggested. The first step consists of estimating the relative health risk associated with each chemical; the estimation is based on the ratio between exposure level and degree of toxicity. Those chemicals representing a high risk are then selected for further consideration. The second step comprises the risk assessment, focusing on prediction of the risk associated with exposure to the mixture of selected chemicals. To allow such prediction the (presumable) mode of action of the selected compounds should be considered. A practical way to find out whether exposure to chemicals at a specific workplace is of serious health concern, could be the conduct of both a 4-week toxicity study in rats and 2 different types of genotoxicity studies with the mixture of selected chemicals, using exposure concentrations related to those occurring in practice.     

The environmental chemical tributyltin chloride (TBT) shows both estrogenic and adipogenic activities in mice which might depend on the exposure dose

Exposure during early development to chemicals with hormonal action may be associated with weight gain during adulthood because of altered body homeostasis. It is known that organotins affect adipose mass when exposure occurs during fetal development, although no knowledge of effects are available for exposures after birth. Here we show that the environmental organotin tributyltin chloride (TBT) exerts adipogenic action when peripubertal and sexually mature mice are exposed to the chemical. The duration and extent of these effects depend on the sex and on the dose of the compound, and the effects are relevant at doses close to the estimated human intake (0.5 μg/kg). At higher doses (50-500 μg/kg), TBT also activated estrogen receptors (ERs) in adipose cells in vitro and in vivo, based on results from acute and longitudinal studies in ERE/luciferase reporter mice. In 3T3-L1 cells (which have no ERs), transiently transfected with the ERE-dependent reporter plus or minus ERα or ERβ, TBT (in a dose range of 1-100 nM) directly targets each ER subtype in a receptor-specific manner through a direct mechanism mediated by ERα in undifferentiated preadipocytic cells and by ERβ in differentiating adipocytes. The ER antagonist ICI-182,780 inhibits this effect. In summary, the results of this work suggest that TBT is adipogenic at all ages and in both sexes and that it might be an ER activator in fat cells. These findings might help to resolve the apparent paradox of an adipogenic chemical being also an estrogen receptor activator by showing that the two apparently opposite actions are separated by the different doses to which the organism is exposed.     

Quantification of Interactions between Serum Albumin and Endogenous Free Fatty Acids or Exogenous Chemicals by Stable Isotope-Coded Mass Spectrometry

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