毒理学基础(一)化学毒物的基本概念

1.化学毒物和毒理学的定义化学毒物是在生物组织中达到一定剂量,能对生物系统产生有害作用,如损伤生理功能或破坏生命的化学物。毒理学是研究化学毒物对生物体毒性作用的科学。随着工业的发展,化学物的种类迅速增加,药物、农药、环境污染物、工业化学物、食品添加剂等日益增多。为了人类的健康、保证安全,要预先估计化学物的毒性,评价其出现毒性的概率。研究毒物作用的性质和机理,有助于采取有效的预防和治疗措施。     

多溴联苯醚的环境污染状况及健康危害研究进展

多溴联苯醚(PBDEs)是一类新型的持久性有机污染物,具有环境持久性、迁移性、生物富集性和生物放大作用等特性,对生物体具有多种毒性效应。笔者综述了近年来PBDEs在各类环境介质和生物体中的检出情况及其对人体的健康危害,并对今后的研究方向进行了展望。     

全氟化合物暴露对骨健康影响的研究进展

全氟化合物（PFASs）是一类全球热点关注的持久性新型有机污染物。PFASs可通过饮水、食物、大气和土壤等环境介质暴露进入人体，在体内持久性蓄积从而引发多种毒性效应。目前，PFASs的骨毒性并未引起重视。研究认为，PFASs的暴露和蓄积对人体骨健康有重大影响，尤其是阻碍婴幼儿和青少年骨骼健康发育，加剧老年人骨丢失和骨折的发生。本文综述了PFASs的暴露浓度对人体骨密度影响的研究进展，探讨PFASs是对骨的毒性机制，以期为揭示PFASs暴露对骨骼健康的影响和毒性机制提供参考。     

全氟辛烷磺酸和全氟辛酸毒理学研究进展

全氟有机化合物,尤其是其代表性化合物全氟辛烷磺酸(PFOS)和全氟辛酸(PFOA)以及它们的盐类作为持久性有机环境污染物新成员,其所造成的全球性生态系统污染已成事实。本文以近年来国内外学者对PFOS和PFOA毒理学研究资料为依据,系统地阐述了PFOS和PFOA在实验动物和人体内的吸收、分布、排泄、代谢和毒物代谢动力学,以及它们对实验动物及人类可能造成的一般毒性、肝脏毒性、神经毒性、心血管毒性、胚胎发育与生殖毒性、遗传毒性与致癌性、免疫毒性等。同时指出,由于种属差异以及一些研究资料的尚不确定性,根据现有资料对PFOA和PFOS进行安全性评价的科学性值得商榷,进一步深入对PFOA和PFOS毒作用敏感指标及毒作用机制的探讨与研究,将成为今后环境科学和预防医学领域的研究重点。     

毒物的联合作用及其卫生标准

随着毒理学的进展,许多国家对多种毒物的毒性进行了研究,并制订了不少单个毒物的卫生标准。但是,环境中往往同时存在着多种毒物,因此必须对毒物的联合作用进行研究并制订混合毒物的卫生标准。在研究混合毒物的毒性之前,应先了解这些物质混合后所发生的理化反应及其对毒性的影响。混合毒物共存时如发生化学反应而产生     

多溴联苯醚健康效应的研究进展

多溴联苯醚是一种在消费品中广泛应用的溴系阻燃剂,由于其具有亲脂性、持久性、远距离迁移性和生物富集等特点,容易在环境和人体中聚积,对人产生健康危害,主要有肝脏毒性、内分泌干扰作用、生殖毒性、免疫毒性和神经毒性等.该文主要从实验研究和人群流行病学调查两方面对近年来国内外关于PBDEs健康效应研究进行综述.     

毒理蛋白质组学与人类健康危险度评价

人类生存环境中存在多种有毒物质,很多相互作用的因素都能对某种环境暴露下的人体健康造成影响.多数毒性反应都涉及到DNA、RNA、蛋白质、代谢产物及它们之间复杂的相互作用.为进行人类健康危险度评价,我们必须了解毒物毒性作用机制及作用方式.     

有机磷阻燃剂生物毒性及相关机制

随着溴化阻燃剂的环境持久性和生物累积毒性均得到进一步证实，其在全球范围内逐步被限制使用。有机磷阻燃剂由于其优良的性能成为溴化阻燃剂的替代品而被广泛应用，同时其对公共健康和生态系统的潜在风险也引起了广泛关注。本文主要总结了有机磷阻燃剂在环境介质中的分布及其暴露所引发的神经毒性、免疫毒性、内分泌干扰毒性、细胞毒性等及相关机制。     

噪声与化学毒物联合作用致听力损伤的研究进展

噪声暴露并非职业性听力损伤的唯一原因，工业化学物的耳毒性作用长期以来未引起重视，研究表明部分化学毒物单独暴露可造成听力系统的损伤，与噪声联合作用可能会产生协同效应，加重听力损伤程度。本文综述了近年国内外噪声、化学毒物致听力损害的机制及二者联合作用的实验室研究和人群流行病学调查资料，并由此提出开展噪声与化学毒物联合作用研究的建议。     

原代肾小管上皮细胞培养技术及其在金属毒理学研究中的应用

原代肾小管上皮细胞培养技术及其在金属毒理学研究中的应用湖南医科大学环境医学研究室谢红（综述）王翔朴（审阅）肾脏是许多金属毒物的主要靶器官和蓄积器官，近年来不断发展的肾小管上皮细胞培养技术为研究金属毒物的毒性、吸收代谢和毒作用机制提供了一种新的手段。由...     

Levels of persistent toxic substances in the general population in Italy

Human exposure to persistent toxic substances (PTS) occurs daily, mainly through diet. As a consequence of continuous exposure, and because of their biological persistence, PTS are virtually present in all individuals, stored in their fatty tissues. The exposure of the Italian general population to PTS is a fact of relevance from a public health perspective, because of the number of toxic effects associated to these compounds, possibly occurring even at the current background level of exposure. In spite of this, data on PTS concentrations in humans, considered the best dose metric to carry out an adequate risk assessment, are scarce, as shown by the overview of available information we hereafter present. The Convention of Stockholm on persistent organic pollutants (POP), a group of highly toxic PTS, has entered into force last May. This will oblige parties to develop national implementation plans, thus creating a new opportunity to develop more efficient policies to control POP and other PTS present in food, humans and the environment.     

Disaster Communication,Posttraumatic Stress,and Posttraumatic Growth following Hurricane Matthew

Disaster survivors may experience a range of mental health reactions that can include posttraumatic stress (PTS) and posttraumatic growth (PTG). The current study examines the associations between citizen disaster communication, PTS, and PTG among individuals in North Carolina communities impacted by Hurricane Matthew, approximately six weeks following the event. Participants who communicated more frequently following the hurricane exhibited more PTS and PTG. Communication activities focused on connecting with loved ones and cognitively restructuring the disaster experience were associated with PTS and PTG, whereas communication activities confirming disaster reports and assisting with disaster recovery were associated solely with PTG. Results illustrate the need for robust disaster communication ecologies to facilitate public disaster mental health response and coordination.     

Studies conducted in Spain on concentrations in humans of persistent toxic compounds

No systematic review is available on studies conducted in Spain on human concentrations of persistent toxic substances (PTS). The objectives were: to identify studies conducted in Spain in the past 30 years that determined concentrations in humans of dichlorodiphenyltrichloroethane (DDT), dichlorodiphenyldichloroethane (DDE), hexachlorobenzene (HCB), hexachlorocyclohexane (HCH) and polychlorinated biphenyls (PCBs); and to summarize the main characteristics and results of each study. Studies are highly heterogeneous and most lack population representativeness. Concentrations of DDT and DDE might have decreased moderately in the last 20 years. Numerous fluctuations are apparent in levels of HCB, HCHs and PCBs, in some instances compatible with some stagnation. There are enormous differences in levels detected across and within studies: PTS concentrations of some individuals may be over 200-fold higher than those of others. The actual magnitude of human contamination by PTS and their trends across Spain -as well as the geographic and social heterogeneity- remain largely unknown.     

Follow-up of hearing thresholds among forge hammering workers

Hearing threshold was reexamined in a group of forge hammering workers investigated 8 years ago with consideration of the age effect and of auditory symptoms. Workers were exposed to impact noise that ranged from 112 to 139 dB(A)—at an irregular rate of 20 to 50 drop/minute—and a continuous background noise that ranged from 90 to 94 dB(A). Similar to what was observed 8 years ago, the present permanent threshold shift (PTS) showed a maximum notch at the frequency of 6 kHz and considerable elevations at the frequencies of 0.25–1 kHz. The age-corrected PTS and the postexposure hearing threshold were significantly higher than the corresponding previous values at the frequencies 0.25, 0.5, 1, and 8 kHz only. The rise was more evident at the low than at the high frequencies. Temporary threshold shift (TTS) values were significantly less than those 8 years ago. Contrary to the previous TTS, the present TTS were higher at low than at high frequencies. Although progression of PTS at the frequencies 0.25 and 0.5 kHz was continuous throughout the observed durations of exposure, progression at higher frequencies occurred essentially in the first 10 to 15 years of exposure. Thereafter, it followed a much slower rate. Tinnitus was significantly associated with difficulty in hearing the human voice and with elevation of PTS at all the tested frequencies, while acoustic after-image was significantly associated with increment of PTS at the frequencies 0.25–2 kHz. No relation between PTS and smoking was found. PTS at low frequencies may provide an indication of progression of hearing damage when the sensitivity at 6 and 4 kHz diminishes after prolonged years of exposure. Tinnitus and acoustic after-image are related to the auditory effect of forge hammering noise.     

A multispecies approach for monitoring persistent toxic substances in the Gulf of Gdańsk (Baltic sea)

Bivalve mussels are usually used for biomonitoring persistent toxic substances (PTS) in coastal ecosystems. Nevertheless, these organisms, which live attached on hard substrates, can be found along the sandy coasts only on human manufactured products. In this work different species collected in the Gulf of Gdańsk were compared to evaluate their suitability for monitoring PTS pollution at a local scale. The clam Mya arenaria seems to represent an excellent indicator of sediment pollution, mainly for organotin compounds which are selectively bioaccumulated. Organochlorine compounds are bioaccumulated in the different species mainly in function of their lipid body burden. Habitat conditions (salinity, substrate, pollution), however, strongly limited the occurrence of different species in the sampling sites; the most ubiquitous species, the common shrimp Crangon crangon, resulted therefore the most suitable to be used for the comparison of PTS pollution in this aquatic environment. Although the blue mussel (Mytilus trossulus) was confirmed to be a very useful sentinel species to compare pollution level inside and outside the Gulf of Gdańsk, we recommend the use of other species to give a more detailed picture of the pollution situation in coastal areas.     

Sodium 2-propenyl thiosulfate derived from garlic induces phase II detoxification enzymes in rat hepatoma H4IIE cells

There is evidence that onions and garlic protect against cancer in humans. It has been suggested that this effect is partly due to the organosulfur compounds in Allium vegetables and that these substances act through induction of phase II detoxification enzymes. Here, we hypothesized that alk(en)yl thiosulfates, sodium n-propyl thiosulfate (NPTS), and sodium 2-propenyl thiosulfate (2PTS), which were identified in onions and garlic, respectively, may induce phase II enzymes. Therefore, rat hepatoma cells (H4IIE) were cultured with 1 to 100 μmol/L of NPTS or 2PTS for 48 hours at 37°C; and the activities and messenger RNA (mRNA) expression levels of phase II enzymes in H4IIE cells were investigated. The effects of diallyl trisulfide and tert-butylhydroquinone, known as phase II inducers, were also examined as positive controls and compared with the responses of NPTS and 2PTS. Quinone reductase (QR) activity and mRNA expression levels of QR and epoxide hydrolase 1 were significantly increased by 2PTS (P < .05-.005). In particular, QR activity was increased at a relatively low concentration of 2PTS (10 μmol/L). However, glutathione S-transferase activity and mRNA expression levels of glutathione S-transferase A5 and uridine diphosphate glucuronosyl transferase 1A1 were not changed by 2PTS. In contrast, NPTS did not affect the activities and mRNA expression levels of these phase II enzymes. These results show that 2PTS can induce phase II enzymes, and its inductive effect is comparable or superior to that of diallyl trisulfide and tert-butylhydroquinone.     

人参三醇组皂苷对运动疲劳大鼠血糖、血乳酸、血尿素氮的影响

目的探讨不同剂量人参三醇组皂苷对运动疲劳大鼠血糖、血乳酸、血尿素氮的影响。方法成熟Wistar大鼠,训练前每日经口灌胃给予PTS高(100.0mg/kg bw)、中(50.0mg/kg bw)、低(25.0mg/kg bw)3个剂量,另设安静对照组、空白训练组(灌胃给予生理盐水)及甲基睾酮组(甲基睾酮水混悬液2.4 mg/kg bw灌胃)。游泳训练7w,观察人参三醇组皂苷对运动疲劳大鼠血糖、血乳酸、血尿素氮的影响。结果甲基睾酮组、人参三醇组皂苷高、中剂量组与空白训练组比较大鼠力竭游泳时间延长,血糖升高差异有统计学意义(均P<0.05);甲基睾酮组、人参三醇组皂苷高剂量组与空白训练组比较血乳酸、血尿素氮浓度降低差异有统计学意义(P<0.05)。结论 PTS对运动疲劳大鼠血糖、血乳酸、血尿素氮有一定影响,能延缓疲劳的产生。     

Exploring the Impact of Racism on Black Youth: A Multidimensional Examination of Discriminatory Experiences Across Place and Time

PurposeCommunity violence disproportionally impacts Black youth. Experiences of racism and discrimination may create additional challenges for youth recovering from violence exposure. This study used ecological momentary assessment to elucidate how perceptions of racism and social support influence health and safety outcomes among Black youth following violence exposure.MethodsTwenty-five Black youth (14–19 years old, 60% female) who had witnessed violence within the past three months completed a baseline survey that assessed discrimination experiences, social support, post-traumatic stress symptoms (PTS), and perceived safety. Youth completed ecological momentary assessments three times daily for two weeks about the place they were in, people they were with, their current emotional state, and in-the-moment racism perceptions. Multilevel models estimated the relationship between overall and time-varying perceptions of racism and social support, PTS symptoms, and perceived safety.ResultsOverall, 76% of youth reported at least one discrimination experience at baseline. Prior discrimination was associated with higher PTS (B = 1.86, p = .001) and depressive symptoms (B = 0.13, p = .013) at baseline. Youth who reported higher overall perceptions of racism in-the-moment reported higher PTS (B = 0.50, p = .002) and lower perceived safety (B = ?0.53, p = .001). In-the-moment perceptions of racism were associated with lower perceived safety in that place (B = ?0.09, p < .01). Emotional and instrumental support were associated with lower PTS and higher perceived safety (p < .05).DiscussionExperiences of racism and being in discriminatory places impacted youth’s depressive symptoms, PTS symptoms, and perceived safety. Interventions attuned to in-the-moment experiences of racism, and that leverage social support, are needed to support Black youth exposed to violence and discrimination.     

Deep vein thrombosis: validation of a patient-reported leg symptom index

Introduction  

Deep vein thrombosis (DVT) is a serious health problem that affects more than 2 million people annually in the United States. Many of these patients develop asymptomatic DVT, but months to years later may experience symptomatic post-thrombotic syndrome (PTS). It is not known how many cases of PTS can be traced to "asymptomatic" DVT because venography is no longer routinely done and ultrasonography (US) may miss some asymptomatic clots. As a result, a clinical tool in addition to US to detect symptom emergence or exacerbation in patients after DVT would be of value.     

Does Maternal Parenting Stress Mediate the Association Between Postpartum PTS Symptoms and Children’s Internalizing and Externalizing Problems? A Longitudinal Perspective

Background

The research carried out in the last years outlined that childbirth could be considered as a sufficient stressor for the insurgence of posttraumatic stress (PTS) symptoms with important consequences for the child care.

Objectives

In a longitudinal perspective, this study focused on PTS symptoms after childbirth to understand their impact on maternal parenting stress and children’s adjustment. First, we investigated whether childbirth-related PTS symptoms, at 87 h and 3 months postpartum, were associated with parenting stress and children’s adjustment at 18 months. Second, we explored, at 18 months, the predictive effects of postpartum PTS symptoms on children’s adjustment and verified the mediational effect of parenting stress this association.

Methods

Eighty-eight women participated and completed the following questionnaires: PPQ (for assessing maternal PTS symptoms at 87 h, 3 and 18 months postpartum), PSI-SF (for maternal parenting stress at 18 months) and CBCL (for children’s adjustment at 18 months).

Results

Findings outlined that more PTS symptoms at 3 months are associated with greater levels of parental distress and they predicted children’s adjustment at 18 months. Moreover, maternal parenting stress explained the predictive effects of childbirth-related PTS symptoms on children’s adjustment. More precisely parental distress partially mediated the association between PTS symptoms and children’s internalizing behaviors, while the perception of the difficult child fully mediated the effects of PTS symptoms on externalizing behaviors.

Conclusion

This study was consistent with the idea that women may experience childbirth-related chronic distress and child adjustment was connected to different sources of parenting stress.