二恶英类毒理学研究新进展

二恶英类的毒理学研究已有30多年的历史,在一系列二恶英类污染事件和国际公约的推动下,近年来二恶英类毒理学研究成为备受关注的热点.综述了近年来二恶英类毒理学研究的一些新的观点和发现,涵盖了分子毒性机理、致癌毒性、非致癌毒性和非致癌剂量-效应风险度评价方法等诸多领域,其中TCDD毒性效应的负反馈调节机制研究和对人体健康非致癌效应的影响引起了国内外广大毒理学研究工作者的关注.在总结前人研究的基础上对二恶英类毒理学研究今后的发展进行了展望.     

PCDDs and PCDFs in food samples from Catalonia, Spain. An assessment of dietary intake

Food samples from local markets and supermarkets of Tarragona (Catalonia, Spain) were analyzed for PCDD/F concentrations. On lipid basis, PCDD/F levels in meat, fish, eggs, and fats and oils were similar or lower than those found in other countries. By contrast, in general terms PCDD/F levels in milk, vegetables, and cereals showed higher levels than those previously reported. The total dietary PCDD/F intake by the population of Tarragona was estimated to be 210 pg I-TEQ/day. This value is higher than the dietary intake of PCDD/Fs found in a number of surveys from other countries. However, when total dietary intake of PCDD/Fs was calculated including only fish and seafood, meat, milk and dairy products, eggs, and fats and oils, a dietary intake of PCDD/Fs of 117 pg I-TEQ/day was obtained. This intake is in the same range than that reported for different regions and countries. The results of the present study show that food groups such as vegetables, fruits, and cereals should not be excluded to estimate the total dietary intake of PCDD/Fs by general populations, especially in those countries and/or regions in which their consumptions are notable.     

The constitutively active Ah receptor (CA-AhR) mouse as a model for dioxin exposure - effects in reproductive organs

The dioxin/aryl hydrocarbon receptor (AhR) mediates most toxic effects of dioxins. In utero/lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) impairs fetal/neonatal development and the developing male reproductive tract are among the most sensitive tissues. TCDD causes antiestrogenic responses in rodent mammary gland and uterus and in human breast cancer cell lines in the presence of estrogen. Also, more recently an estrogen-like effect of TCDD/AhR has been suggested in the absence of estrogen. A transgenic mouse expressing a constitutively active AhR (CA-AhR) was developed as a model mimicking a situation of constant exposure to AhR agonists. Male and female reproductive tissues of CA-AhR mice were characterized for some of the effects commonly seen after dioxin exposure. Sexually mature CA-AhR female mice showed decreased uterus weight, while an uterotrophic assay in immature CA-AhR mice resulted in increased uterus weight. In immature mice, both TCDD-exposure and CA-AhR increased the expression of the estrogen receptor target gene Cathepsin D. When co-treated with 17β-estradiol no increase in Cathepsin D levels occurred in either TCDD-exposed or CA-AhR mice. In sexually mature male CA-AhR mice the weights of testis and ventral prostate were decreased and the epididymal sperm reserve was reduced. The results of the present study are in accordance with previous studies on dioxin-exposed rodents in that an activated AhR (here CA-AhR) leads to antiestrogenic effects in the presence of estrogen, but to estrogenic effects in the absence of estrogen. These results suggest the CA-AhR mouse model as a useful tool for studies of continuous low activity of the AhR from early development, resembling the human exposure situation.     

Blood dioxin biomonitoring to assess local residents' exposure from a large urban remediation project

Background

A total of 265 000 m³ of dioxin contaminated soil and sediments from past industrial activity was treated on site in an urban setting in Sydney, Australia. To respond to local community concerns about potential dioxin exposure from fugitive emissions a human biomonitoring study was undertaken.

Objective

To determine whether local residents were exposed to significant amounts of dioxin from the remediation process.Methods: Blood samples were collected from local residents around the site and a representative metropolitan control group. They were pooled within age and sex strata and the change in dioxin concentrations over the remediation period and a summary of the mid point and post remediation dioxin concentrations were compared between groups. Information on dietary intake was collected to look for possible confounding.

Results

The mean dioxin Toxic Equivalent concentrations (TeQ) decreased among both the local resident and control groups over the remediation period by 1.9 and 2.1 pg gm⁻¹ lipid respectively. Modelled blood concentrations adjusting for age and sex did not detect a significant difference between groups for changes in either TeQ or 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8 TCDD). The summary measure approach did however demonstrate that the 2,3,7,8 TCDD concentrations among the local resident group was approximately 0.7 pg g⁻¹ lipid higher compared to the control group post remediation. There were no significant changes in dietary intake sources of dioxin.

Conclusion

Biomonitoring demonstrated that local residents were not exposed to significant quantities of dioxin. Large scale remediation of dioxin contaminated land can be safely undertaken in an urban setting.     

Colloid facilitated transport of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) to the groundwater at Ma Da Area, Vietnam

PCDD/Fs are hydrophobic organic substances and strongly sorbing to soil particles. Once adsorbed to soil particles they are believed to be virtually immobile. However, research in the last decades confirmed that strong sorbing contaminants may reach the groundwater via colloid-facilitated transport. This pathway has not been investigated before in Vietnam. Ma Da area, 100 km north of Ho Chi Minh City, was repeatedly sprayed during the Vietnam War (1962–1971) with herbicides like Agent Orange containing, beside others, the teratogenic contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). 11 surface soil samples and 12 water samples were collected in Ma Da area for analysis of PCDD/Fs in solids. Soil TCDD concentrations ranged from 1–41 ppt with a mean of 8.8 ppt and a mean I-TEQ of 9.7 ppt. Two surface water samples showed colloid bound TCDD (7 and 19 ppt). Groundwater samples showed elevated colloid bound PCDD concentrations (mean 770 ng/kg), mainly octachlorodibenzo-p-dioxin. Groundwater colloids separated by filtration did not show any TCDD. The results support that TCDD/Fs can be relocated from the top soil to the groundwater by colloidal pathway. They did not provide evidence that the dioxins bound to groundwater colloids are leftovers from the Second Indochinese War. However, this study reinforces that the colloidal transport pathway has to be included investigating the relocation of strong sorbing organic contaminants.     

Melting and incineration plants of municipal waste. Chemical and biochemical diagnosis of thermal processing samples (emission,residues)

Control of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs) in emissions and thermal residues from incinerators has been a cause of public concern for more than one decade. Recently, several studies showed that other persistent organic pollutants (POPs) such as coplanar polychlorinated biphenyls (co-PCBs) also have dioxin-like activity and are released from incinerators. Therefore, the present study was aimed at making a risk assessment about dioxin-like activity in extracts of thermal waste residues (e.g. combustion gas; fly ash, slag) from incineration and melting processes in Germany and Japan. For this purpose, polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs), coplanar polychlorinated biphenyls (co-PCBs), polychlorinated naphthalenes (PCNs) and polyaromatic hydrocarbons (PAHs) were analyzed by chemical analysis. Additionally, 2, 3, 7, 8-TCDD equivalents (EROD-TEQs) were determined by in vitro Micro-EROD bioassay using rat H4IIE hepatoma cells. EROD-TEQs could be correlated to I-TEQ values (from PCDD/Fs/co-PCBs) analyzed by chemical analysis resulting in a maximal sixfold higher estimate. Our study indicates minor influences of co-PCBs, PAHs and PCNs to the sum of dioxin-like toxicity in the extracts of thermal waste residues as determined here. Furthermore, we showed that the levels of dioxins and co-PCBs contained in slag from melting processes and bottom ashes from incineration processes were lower by 1-2 orders of magnitude than that in fly ash.     

Fractal and multifractal approach to environmental pollution

A few case studies will be presented involving both radioactive and chemical pollution at small, medium, and large space-time scales. Reported are recent advances in the field of environmental pollution involving the use of fractals and multifractals. The mathematical tools proposed here may offer new perspectives for investigating many of the problems of nonlinear variability which commonly arise when dealing with pollutants, such as the presence of outliers and the sparseness of the sampling networks. They may also lead to a simplification of the models adopted for studying natural phenomena, thanks to a scaling approach. Finally, they may provide parameters whose values are directly related to the nonlinear dynamics involved in the pollutant distribution in the environment which, in turn, may be relevant for computer simulation and epidemiological or risk assessment purposes.     

Bioassay zur Bestimmung von TCDD-Toxizit?ts?quivalenten (TEQ) von Umweltproben und Reststoffen

Zusammenfassung  Polychlorierte aromatische Kohlenwasserstoffe (PHAK), z.B. 2,3,7,8-Tetrachlordibenzo-p-dioxin (TCDD), weisen eine Vielzahl von toxischen Wirkungen und biologischen Effekten auf. Die Substanzklasse der PHAK besitzt die Eigenschaft der Bindung an ein cytosolisches Rezeptor-Protein, gefolgt von der Synthese bestimmter Genprodukte, u.a. von Cytochrom P450 1A1 (CYP 1A1). In dieser Arbeit wird ein Bioassay beschrieben, der erlaubt, die Induktion von CYP 1A1 als Summenparameter für die biologische Wirksamkeit der kritischen, halogenierten Verbindungen in komplexen Umweltmatrizes zu bestimmen. Zur Abtrennung von Substanzen aus den Extrakten von Umweltproben (z. B. Naturstoffe und polyzyklische aromatische Kohlenwasserstoffe), die den Bioassay st?ren k?nnen, wurde ein Ein-S?ulen-Clean-up entwickelt. Die biologisch ermittelten TEQ-Werte stimmen gut mit den Resultaten der chemischen Analytik überein. Der Bioassay in Kombination mit dem Clean-up bietet eine zeitsparende und kostengünstige M?glichkeit zur Untersuchung von Umweltproben.      

Hepatoprotective and antioxidant effects of dietary Glycyrrhiza polysaccharide against TCDD-induced hepatic injury and RT-PCR quantification of AHR2, ARNT2, CYP1A mRNA in Jian Carp (Cyprinus carpio var. Jian)

To evaluate the protective effects of Glycyrrhiza polysaccharide (GPS) against 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced hepatotoxicity in Jian carp, the fish were fed diets containing GPS at doses of 0.1, 0.5 and 1.0 g/kg for 60 days before an intraperitoneal injection of 0.6 μg/kg TCDD at a volume of 0.05 mL/10 g body weight. At 72 hr post-injection, blood and liver samples were taken for biochemical analysis and the fish liver samples were used for the preparation of pathological slices. The results showed that increases in alanine aminotransferase (GPT), aspartate aminotransferase (GOT), lactate dehydrogenase (LDH), and alkaline phosphatase (AKP) in serum induced by TCDD were significantly inhibited by pre-treatment with 1.0 g/kg GPS. Following the 1.0 g/kg GPS pre-treatment, total protein (TP), albumin (Alb), catalase (CAT), glutathione peroxidase (GPx), total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) activities in liver tissue increased significantly, malondialdehyde (MDA) formation (P < 0.05 or P < 0.01) was significantly inhibited, and the expression of cytochrome P4501A (CYP1A), aryl hydrocarbon receptor 2 (AHR2) and aryl hydrocarbon receptor nuclear translocator 2 (ARNT2) mRNA (P < 0.05) was significantly enhanced. Histological observations on fish liver were obtained by preparing paraffin tissue sections via HE staining, and the results showed that histological changes were obviously reduced by 0.5 and 1.0 g/kg GPS. GPS significantly reduced liver tissue damage caused by TCDD. Overall, these results proved the hepatoprotective effect of GPS in protecting against fish liver injury induced by TCDD, and supported the use of GPS (1.0 g/kg) as a hepatoprotective and antioxidant agent in fish.