Low level inhalation experiments with four different cadmium compounds in rats†

This long‐term inhalation study was designed to describe the toxicity and the carcinogenic risk from Cd compounds because it had been shown from former long‐term inhalation studies that cadmium choloride induced primary lung tumors in Wistar rats. It was therefore logical to examine whether other cadmium compounds to which human beings are more frequently exposed have also carcinogenic potency. In a long‐term inhalation study cadmium aerosols consisting of cadmium chloride (CdCl₂), cadmium oxide (CdO) as dusts and fumes, cadmium sulfate (CdSO₄), cadmium sulfide (CdS) and a combination of cadmium oxide/zinc oxide were used. Wistar rats were continuously exposed in inhalation chambers for 18 months 22 hrs a day or for 40 hrs a week. The studies will be terminated at the mean survival life time of the species. The aerosols were generated by several different systems. The particles of the cadmium aerosols have the average mass medium diameters in the range from 0.2 to 0.5 μm.     

镉致癌的分子机制研究进展

镉是一种无处不在的重金属环境污染物,广泛用于工业环境中。普通人主要通过摄食、吸烟及饮水等方式摄入镉。1993年国际肿瘤研究机构(IARC)就已将镉及其化合物列为第1类人致癌物,镉的致癌性被广泛研究,大量研究发现镉会提高肺癌、前列腺癌、乳腺癌、消化道肿瘤等肿瘤的患病风险。但至目前为止,镉的致癌分子机制尚不清楚。大量研究认为镉通过以下几方面致癌:氧化应激、抑制DNA损伤修复、DNA异常甲基化、抑制细胞凋亡、影响细胞周期调控、致多种基因异常表达、雌激素样效应、促进肿瘤干细胞生长、慢性炎症刺激。     

Metals in the indoor environment

There is a growing recognition that individual exposures to a broad spectrum of metal, inorganic and organic pollutants exceed those from ambient and in some cases from the vicinity of industry environments. The agents often found in indoor environments are mostly known to be hazardous in high concentrations, but the lower limit of their dose response relationships are poorly defined.

The major sources of metals in indoor environments are cigarette smoke (mainstream and side stream), fuel combustion, house dust and consumer products with arsenic, cadmium, lead and nickel being of primary toxicological potential (i.e. carcinogenic, genotoxic and reproductive development). Aspects of levels and duration of human exposure to these elements in relation to existing body burdens and subsequent bioavailability and interactions are generally poorly known from inhalation sources.

Although the magnitude of indoor health hazards to metallic constituents is not now known, mounting evidence suggests that both identification of agents and the measurement of indoor exposures are critical for a more realistic assessment of the effect of this aspect of air pollution on human health.     

Correlation of cadmium and aluminum in blood samples of kidney disorder patients with drinking water and tobacco smoking: related health risk

The combined exposure to aluminum (Al) and cadmium (Cd) causes more pronounced adverse health effects on humans. The kidneys are the main organs affected by internal exposure to Cd and Al via food and non-food items. The objective of present study was to measure the Al and Cd concentrations in cigarettes tobacco (branded and non-branded) and drinking water (domestic treated, ground and lake water) samples in southern part of Pakistan, to assess the risk due to ingestion of water and inhalation of cigarettes smoke containing high concentrations of both elements. The study population (kidney disorder and healthy) divided into two group based on consuming lake and ground water, while smoking non-branded cigarette as exposed, while drinking domestic treated water and smoking branded cigarette as non-exposed. Electrothermal atomic absorption spectrometry was used to determined Cd and Al concentrations in tobacco, drinking water and blood samples. The resulted data indicated that the levels of Al and Cd in lake and underground water were higher than the permissible limit in drinking water recommended by the World Health Organization. The biochemical parameters of exposed and referent patients, especially urinary N-acetyl-h-glucosaminidase, were used as a biomarkers of kidney disorder. Exposed kidney disorder patients have higher levels of Cd and Al than the exposed referents subjects, while difference was significant when compared to resulted data of non-exposed patients and referents (p = 0.01–0.001). The pearson correlation showed positive correlation between both toxic element concentrations in water, cigarettes versus blood samples of exposed subjects (r = 0.20–0.67 and 0.71–0.82), while lower values were observed for non-exposed subjects (r = 0.123–0.423 and 0.331–0.425), respectively.

     

Chemical characterization and health risk assessment of soil and airborne particulates metals and metalloids in populated semiarid region,Agra, India

Rapid industrialization and urbanization have contaminated air and soil by heavy metals and metalloids from biogenic, geogenic and anthropogenic sources in many areas of the world, either directly or indirectly. A case study was conducted in three different microenvironments, i.e., residential sites, official sites and official sites; for each sites, we choose two different locations to examine the elemental concentration in fine particulate matter and soil and health risk assessment. The concentration values of heavy metals and metalloid in the air and soil in the Agra region were measured using inductively coupled plasma-atomic emission spectrophotometry. The exposure factor and health risk assessment for carcinogenic and non-carcinogenic effects due to heavy metals and metalloid contaminants have been calculated for both children and adults by following the methodology prescribed by USEPA. For the elements As, Cr, Cd, Ni and Pb selected for the carcinogenic health risk assessment, the calculated results lie above the threshold ranges. We observed the lifetime exposure to heavy metals through mainly three pathways, ingestion, inhalation and dermal contact of soil and air from that particular area. Therefore, the overall hazard quotient (HQ) values for children are more than that of adults. The assessment of health risk signifies that there were mainly three exposure pathways for people: ingested, dermal contact and inhalation. The major exposure pathway of heavy metals to both children and adults is ingestion. The values of HQ are higher than the safe level (=1), indicating a high risk exists in present condition. Meanwhile, HQs value for children is higher than that for adults, indicating that children have higher potential health risk than adults in this region.

     

Plant extract reduces tobacco smoke harmful effects on alveolar macrophage immune responses

Tobacco smoke is a major factor responsible for lung cancer and chronic obstructive pulmonary disease. Although the best solution to reduce the incidence of these diseases is to quit smoking, there are still a large number of smokers. Thus, given the immunoregulatory properties of plant extracts, their capacity to reduce tobacco smoke harmful effects on alveolar macrophage (AM) functions was investigated. AM were treated with tobacco smoke extract and parenchymata tissue extract (PTE), or mesophyll cell extract (MCE) of Spinacia oleacea. The effects of tobacco smoke extract from PTE and MCE-treated cigarette filters were also investigated. AM production of tumor necrosis factor (TNF), interleukin-10 (IL-10) and macrophage chemoattractant protein-1 (MCP-1), and AM cytotoxicity were measured. Tobacco smoke extract significantly inhibited TNF, IL-10, and MCP-1 release, and AM cytotoxicity. The addition of PTE and MCE to tobacco smoke extract abrogated the inhibition of AM mediator release. However, only MCE restored AM cytotoxicity. Interestingly, tobacco smoke extract of PTE and MCE-treated cigarette filters showed reduced effects on AM functions. Tobacco smoke extract from MCE-treated (0.25%) cigarette filters did not inhibit TNF, IL-10, and MCP-1 release in contrast to tobacco smoke extract from buffer-treated cigarette filters. AM cytotoxic activity was not inhibited by the treatment with tobacco smoke extract from MCE-treated cigarette filters. Our data suggest that the presence of plant extract in cigarette filters reduces the inhibitory effects of cigarette smoke on AM functions. Thus, MCE-treated cigarette filters may help reducing lung diseases associated with smoking.     

Metal Interactions in carcinogenesis†

Mixed exposures to a number of metallic compounds may give rise to a carcinogenic response in humans.

An interaction between occupational exposure to arsenic and cigarette smoking has been documented epidemiologically. A multiplicative effect was indicated concerning the occurrence of lung cancer when both of the exposures were present. Several experimental studies have been reported in the literature concerning interactions between benzo(a)pyrene and Fe₂O₃ as well as some other metallic compounds like Ni₃S₂, PbO, MgO and TiO₂ in relation to respiratory carcinogenicity. There is also limited evidence of a positive interaction between arsenic trioxide and benzo(a)pyrene. Particles containing V and Ni were obtained from the flue gases of power plants burning heavy fuel oil. Such particles were not carcinogenic themselves but enhanced the carcinogenicity of benzo(a)pyrene even more efficiently than Fe₂O₃.

Increased dietary selenium intakes can decrease the carcinogenicity of several organic carcinogens in animals and dietary zinc can effectuate both enhancement and inhibition of carcinogenicity depending on dietary concentration.     

Human lung injury following exposure to humic substances and humic-like substances

Among the myriad particles the human respiratory tract is exposed to, a significant number are distinctive in that they include humic substances (HS) and humic-like substances (HULIS) as organic components. HS are heterogeneous, amorphous, organic materials which are ubiquitous occurring in all terrestrial and aqueous environments. HULIS are a complex class of organic, macromolecular compounds initially extracted from atmospheric aerosol particles which share some features with HS including an aromatic, polyacidic nature. As a result of having a variety of oxygen-containing functional groups, both HS and HULIS complex metal cations, especially iron. Following particle uptake by cells resident in the lung, host iron will be sequestered by HS- and HULIS-containing particles initiating pathways of inflammation and subsequent fibrosis. It is proposed that (1) human exposures to HS and HULIS of respirable size (<10 µm diameter) are associated with inflammatory and fibrotic lung disease and (2) following retention of particles which include HS and HULIS, the mechanism of cell and tissue injury involves complexation of host iron. Human inflammatory and fibrotic lung injuries following HS and HULIS exposures may include coal workers’ pneumoconiosis, sarcoidosis, and idiopathic pulmonary fibrosis as well as diseases associated with cigarette smoking and exposures to emission and ambient air pollution particles.     

Effects of cigarette and biomass smoke exposure on oxidant–antioxidant status in rabbits

To evaluate the effects of cigarette smoking and biomass (dried dung) smoke on the oxidant–antioxidant status, three groups each with 5 rabbits were used. Groups of rabbits were exposed to either cigarette smoke, dried dung smoke or dry air, 1?h daily for one month. Protein carbonyls, prostaglandin F_2α and malondialdehyde levels were significantly increased and protein sulfhydryls levels were significantly decreased in the cigarette smoke group compared with the control group. Only protein sulfhydryls levels were significantly decreased in dung group compared with the control group. Short course exposure to both cigarette smoke and biomass smoke decreased plasma antioxidant levels but only cigarette smoke increased plasma oxidant levels, whereas biomass smoke did not produce any change.     

电镀企业周边大气颗粒物PM_(2.5)、PM_(10)和TSP中重金属分布特征及健康风险评价

以东莞市5个镇区为研究对象,采集电镀企业周边大气样品,分析了样品中重金属(包括As、Co、Cd、Cr、Cu、Mn、Ni、Pb、Sb、V、Zn和Hg)的含量分布,使用富集因子(enrich factor)、地累积指数(index of geoaccumulation)、Hakanson法和美国国家环境保护局(US EPA)的人体暴露健康风险评价模型,对PM_(2.5)、PM_(10)、总悬浮颗粒物(TSP)中重金属进行人体健康风险评价。结果表明,PM_(2.5)、PM_(10)和TSP中As、Cd和Cr平均浓度皆超标。Cr、Ni和V元素在3种颗粒物中非富集,主要为自然源;As、Co、Cu、Pb和Zn,可能来源于自然源和叠加的工业污染。Cd、Hg和Sb浓度受人为污染影响严重。Cd、Sb、Cu、Zn、Pb为生物可利用元素(K>0.6),在环境中的可迁移性高且易于被生物体和人体吸收。Mn元素的非致癌风险值较其他重金属要高1~4个数量级,且儿童的非致癌暴露风险值HQ均高于成人的。3种颗粒物中重金属元素通过呼吸吸入途径产生的非致癌风险HI值均高于人体可接受的上限1.0,其主要贡献来源于Mn的影响,研究区非致癌风险较为严重。除PM_(10)中Co元素和TSP中Co、Cr的成人致癌风险CR值大于10-4之外,其余大部分重金属元素通过呼吸途径产生的致癌风险CR值均在可接受范围之内,此外,3种颗粒物中的成人的致癌暴露风险值CRT均高于儿童的CRT值,并且除了PM_(2.5)中儿童的重金属致癌暴露风险CRT值(4.70E-05)低于人体可接受范围的上限(10-4),其余CRT值均高于10-4,致癌风险较为严重。     

Status,source identification,and health risks of potentially toxic element concentrations in road dust in a medium-sized city in a developing country

This study aims to determine the status of potentially toxic element concentrations of road dust in a medium-sized city (Rawang, Malaysia). This study adopts source identification via enrichment factor, Pearson correlation analysis, and Fourier spectral analysis to identify sources of potentially toxic element concentrations in road dust in Rawang City, Malaysia. Health risk assessment was conducted to determine potential health risks (carcinogenic and non-carcinogenic risks) among adults and children via multiple pathways (i.e., ingestion, dermal contact, and inhalation). Mean of potentially toxic element concentrations were found in the order of Pb > Zn > Cr(IV) > Cu > Ni > Cd > As > Co. Source identification revealed that Cu, Cd, Pb, Zn, Ni, and Cr(IV) are associated with anthropogenic sources in industrial and highly populated areas in northern and southern Rawang, cement factories in southern Rawang, as well as the rapid development and population growth in northwestern Rawang, which have resulted in high traffic congestion. Cobalt, Fe, and As are related to geological background and lithologies in Rawang. Pathway orders for both carcinogenic and non-carcinogenic risks are ingestion, dermal contact, and inhalation, involving adults and children. Non-carcinogenic health risks in adults were attributed to Cr(IV), Pb, and Cd, whereas Cu, Cd, Cr(IV), Pb, and Zn were found to have non-carcinogenic health risks for children. Cd, Cr(IV), Pb, and As may induce carcinogenic risks in adults and children, and the total lifetime cancer risk values exceeded incremental lifetime.     

Toxicity of cigarette smoke on isolated lung,heart, and brain mitochondria: induction of oxidative stress and cytochrome c release

Cigarette smoking is one of the main risk factors for premature human death which is associated with a variety of respiratory and vascular diseases, and cancer due to exposure to hundreds of toxicants. Rat mitochondria were obtained by differential ultracentrifugation and incubated with different concentrations (1%, 10%, or 100%) of standardized cigarette smoke extract (CSE). Our results showed that CSE induced a rise in mitochondrial reactive oxygen species (ROS) formation, lipid peroxidation, and mitochondrial membrane potential (MMP) collapse before mitochondrial swelling ensued in isolated pulmonary mitochondria. Disturbance in oxidative phosphorylation was also confirmed by decrease in ATP concentration in the CSE-treated mitochondria. In addition, collapse of MMP and mitochondrial swelling produced release of cytochrome c via outer membrane rupture or mitochondrial permeability transition (MPT) pore opening. Our results suggested that CSE-induced toxicity in lung tissue is the result of disruptive effect on mitochondrial respiratory chain that leads to ROS formation, lipid peroxidation, MMP decline, and cytochrome c expulsion which results in apoptosis signaling and cell loss.     

Chemical analysis of tobacco cigarette for organochlorine insecticides and heavy metal composition

The effects of cigarette smoking on smokers and the environment were investigated by analyzing some cigarette brands available to Nigerian smokers for the presence of some of the widely used organochlorine (OC) pesticides and heavy metals. OC pesticide residues were extracted from tobacco smoke, separated and identified using column chromatographic and thin layer chromatographic techniques respectively, while ashed and unashed commercial cigarettes were analyzed for heavy metals – Cr, Mn, Ni, Pb, Zn, Cd, Cu, and Co using atomic absorption spectrometry. TLC data indicated that dieldrin and p,p′-DDD were present in some of the cigarette brands. The results of heavy metal analysis showed that the levels of some toxic heavy metals and pollution index were higher in unashed cigarettes than corresponding ashes. Evidence suggests that significant amounts of these toxic metals are inhaled by the smoker and/or released into the environment in the process of cigarette smoking, thus confirming that cigarette smoking is harmful to the environment and human health.     

Mutagenic and carcinogenic effects of cadmium†

There is limited evidence to suggest that certain compounds of cadmium may be mildly mutagenic. Some compounds of cadmium have given rise to fibrosarcoma and rhabdomyosarcoma following subcutaneous or intramuscular injection in the rat and also to interstitial cell tumours of the testis as a sequel to cellular damage and testicular atrophy. Cadmium chloride aerosol inhalation has induced a high incidence of dose‐related lung cancer in the rat. Epidemiological observations suggest that mortality from prostatic and possibly from lung cancer has been increased in cadmium workers who had experienced the very high levels of cadmium, mainly as oxide dust or fume, which existed in the past. The more recent epidemiological studies have not added further evidence in support of the carcinogenic role of cadmium.     

甲苯二异氰酸酯(TDI)致癌性的综合评估

甲苯二异氰酸酯(TDI)被数家机构分类为可能的人类致癌物,其主要依据为动物实验发现对啮齿动物经灌胃暴露TDI后肿瘤发生率升高。基于研究结果的可靠性以及一致性,综合评估了现有研究数据是否支持这一分类。结果显示现有的流行病学数据不足以有力证明TDI为人类致癌物。动物实验研究表明,吸入接触TDI并不导致肿瘤发生。经灌胃暴露后观察到的肿瘤很可能是由于TDI转化为已知的啮齿动物致癌物甲苯二胺(TDA)所致。在TDI吸入暴露的体内实验中,当由TDI转化生成的TDA不能达到具有显著生物学效应的浓度时,TDI对啮齿动物或人类都没有遗传毒性。由于哺乳动物在生理性接触条件下TDI不能转变成TDA,所以对人类而言,TDI接触与致癌效应之间无直接的显著因果关系。因此虽然在如灌胃等非生理暴露的条件下,TDI可能的人类致癌物的分类是正确的,但本文对其致癌研究数据的合理评估和正确理解有助于将产品监管力度集中于与职业暴露更相关的有害健康效应上。     

空气中超细颗粒物检测方法的研究进展

颗粒物的健康损害效应已得到广泛的关注。尤其近年来,国内外学者们针对PM2.5等大颗粒开展了大量的人群流行病学和毒理学研究,健康损害效应的因果关系得到基本确认。然而比PM2.5粒径更小但数量更多的超细颗粒物(UFPs),其暴露特征及对健康影响的贡献值尚不清楚,缺乏统一的检测方法及策略是影响其健康评估的关键因素。因此,本文根据国内外文献,综述了目前超细颗粒物的检测方法、仪器及策略,总结了超细颗粒物评价方法的影响因素及其存在的不足,为超细颗粒物检测方法的进一步研究提供建议和帮助。     

Indoor and outdoor air pollution and lung cancer in New Hampshire and Vermont

Indoor and outdoor air pollution is known to contribute to increased lung cancer incidence. This study is the first to address the contribution of home heating fuel and geographical course particulate matter (PM₁₀) concentrations to lung cancer rates in New Hampshire, USA. First, Pearson correlation analysis and geographically weighted regression were used to investigate spatial relationships between outdoor PM₁₀ and lung cancer rates. While the aforementioned analyses did not indicate a significant contribution of PM₁₀ to lung cancer in the state, there was a trend towards a significant association in the northern and southwestern regions of the state. Second, case-control data were used to estimate the contributions of indoor pollution and secondhand smoke to the risk of lung cancer with adjustment for confounders. Increased risk was found among those who used wood or coal to heat their homes for more than 10 winters before the age of 18, with a significant increase in risk per winter. Resulting data suggest that further investigation of the relationship between heating-related air pollution levels and lung cancer risk is needed.     

Enhancement of radon exposure in smoking areas

Radium-226 is a significant source of radon-222 which enters buildings through soil, construction materials or water supply. When cigarette smoke is present, the radon daughters attach to smoke particles. Thus, the alpha radiation to a smoker’s lungs from the natural radon daughters is increased because of smoking. To investigate whether the cigarette tobacco itself is a potential source of indoor radon, the α potential energy exposure level contents of radon (²²²Rn, 3.82d) and Thoron (²²⁰Rn, 55.60s) were measured in 10 different cigarette tobacco samples using CR-39 solid-state nuclear track detectors (SSNTDs). The results showed that the ^{222, 220}Rn concentrations in these samples ranged from 128 to 266 and 49 to 148 Bqm⁻³, respectively. The radon concentrations emerged from all investigated samples were significantly higher than the background level. Also, the annual equivalent doses from the samples were determined. The mean values of the equivalent dose were 3.51 (0.89) and 1.44 (0.08) mSvy⁻¹, respectively. Measurement of the average indoor radon concentrations in 20 café rooms was, significantly, higher than 20 smoking-free residential houses. The result refers to the dual (chemical and radioactive) effect of smoking as a risk factor for lung cancer.     

Inorganic arsenic compounds: are they carcinogenic,mutagenic, teratogenic?

This review examines and evaluates the literature on the ability of inorganic arsenic compounds to cause cancer in humans and laboratory animals. The epidemiological data that supports the position that inorganic arsenical derivatives are carcinogenic in humans is convincing and difficult to deny because of their consistency. These data are from studies of different occupational exposures such as smelter and pesticide workers, as well as from studies of drinking water, wines and medicinal tonics that contained or were contaminated with inorganic compounds of arsenic. Indeed, positive dose-response relationships between cancer incidence or mortality with many inorganic arsenical substances have been shown. Despite the presence of data which confuse the interpretation and evaluation of epidemiological data, associated neoplasms of the lungs, skin and gastrointestinal systems have been observed as a result of exposure to inorganic arsenic compounds.The mechanism of carcinogenicity of inorganic arsenical substances in humans is unknown. Inorganic arsenic compounds are not carcinogenic in laboratory animals by most routes of administration. However, further studies (subchronic, chronic, carcinogenic) using intratracheal and other conventional routes in other animal species would appear to be warranted. Moreso, especially since there is no evidence that organic arsenic compounds are carcinogenic in numerous mammalian species. Inorganic derivatives of arsenic are not mutagenic but may be teraiogenic. This latter conclusion is dependent on the method of administration and size of the dose, as well as on the species of animal used for the study.     

Cadmium and chromium in human lung tissue in relation to smoking and lung cancer

The pulmonary Cd and Cr content was determined from 53 lung cancer patients operated for cancer and from 39 patients who died of non‐malignant diseases. The results were correlated with smoking habits, pulmonary emphysema and occupational history. Both the pulmonary Cd and Cr increased with the amount of smoking. In ex‐smokers the Cr content in lung tissue did not diminish with the time since stopping smoking, but the Cd did follow the half‐life of about 9 years. The pulmonary Cd, compared with smoking habits, behaved similarly in both the lung cancer and control patients, whereas Cr in the lung cancer patients could not be explained solely by smoking, but some of the cancer patients may have been occupationally exposed to Cr. Speciation was not studied.