Xenobiotic-contaminated diets affect hepatic lipid metabolism: Implications for liver steatosis in Sparus aurata juveniles.

The metabolic effects induced by feed contaminated with a lower or a higher concentration of -nonylpnenol (NP), 4-tert-octylphenol (t-OP) or bisphenol A (BPA), three environmental endocrine disruptors, were assessed in juvenile sea bream liver. Histological analysis demonstrated that all these three xenobiotics induced hepatic lipid accumulation and steatosis. These findings prompted analysis of the expression of the major molecules involved in lipid metabolism: peroxisome proliferator activated receptors (which is encoded by ppars), fatty acid synthase (encoded by fas), lipoprotein lipase (encoded by lpl) and hormone-sensitive lipase (encoded by hsl). The enzymes encoded by ppars and fas are in fact responsible for lipid accumulation, whereas lpl- and hsl- encoded proteins play a pivotal role in fat mobilization. The three xenobiotics modulated ppar mRNA expression: pparα mRNA expression was induced by the higher dose of each contaminant; pparß mRNA expression was upregulated by the lower doses and in BPA2 fish ppary mRNA overexpression was induced by all pollutants. These data agreed with the lipid accumulation profiles documented by histology. Fas mRNA levels were modulated by the two NP doses and the higher BPA concentration. Lpl mRNA was significantly upregulated in all experimental groups except for BPA1 fish while hsl mRNA was significantly downregulated in all groups except for t-OP2 and BPA1 fish. The plasma concentrations of cortisol, the primary stress biomarker, were correlated with the levels of pepck mRNA level. This gene encodes phosphoenolpyruvate carboxykinase which is one of the key enzymes of gluconeogenesis. Pepck mRNA was significantly overexpressed in fish exposed to NP2 and both t-OP doses. Finally, the genes encoding cyclooxygenase 2 (cox2) and 5-lipoxygenase (5 lox), the products of which are involved in the inflammatory response, transcriptions were significantly upregulated in NP and BPA fish, whereas they were unchanged in t-OP specimens. The present findings suggest that dietary xenobiotic contamination can give rise to metabolic disorders also in fish and highlight the potential for their vertical transfer through the trophic levels and ultimately to humans.

Waste management health risk assessment: a case study of a solid waste landfill in South Italy.

An integrated risk assessment study has been performed in an area within 5 km from a landfill that accepts non hazardous waste. The risk assessment was based on measured emissions and maximum chronic population exposure, for both children and adults, to contaminated air, some foods and soil. The toxic effects assessed were limited to the main known carcinogenic compounds emitted from landfills coming both from landfill gas torch combustion (e.g., dioxins, furans and polycyclic aromatic hydrocarbons, PAHs) and from diffusive emissions (vinyl chloride monomer, VCM). Risk assessment has been performed both for carcinogenic and non-carcinogenic effects. Results indicate that cancer and non-cancer effects risk (hazard index, HI) are largely below the values accepted from the main international agencies (e.g., WHO, US EPA) and national legislation (D.Lgs. 152/2006 and D.Lgs. 4/2008).

Environmental exposure to polychlorinated biphenyls (PCBs) and breast cancer: a systematic review of the epidemiological evidence.

Some PCB congeners have shown oestrogenic effects, and this has raised concern that they may increase the risk of breast cancer. In this article we provide a quantitative review of the epidemiologic evidence on environmental exposure to PCBs and breast cancer risk. The vast majority of prospective and retrospective studies did not find any association between total PCB concentrations and breast cancer risk. No association was found for congeners in groups I (potentially oestrogenic) and III (biologically persistent phenobarbital-type cytochrome P450 inducers), according to the classification proposed by Wolff and Toniolo, while less consistent results were reported for group II (potentially anti-oestrogenic and immunotoxic, dioxin-like). Two studies found a threefold risk of postmenopausal breast cancer for women with an A2455G base change in exon 7 of the polymorphic CYP1A1 gene (a member of the cytochrome P450 family) and high PCB levels, compared with women with two wild-type alleles and low PCB, based however on very few cases. Thus, the epidemiological evidence does not support the hypothesis of an association of environmental exposure to PCBs in adulthood in the general population and risk of breast cancer, although uncertainties remain for selected subgroups of women or individual PCB congeners.

Occupational exposure to polychlorinated biphenyls and cancer risk.

Polychlorinated biphenyls (PCBs) are a class of chemicals characterized by a long-term persistence and diffusion in the environment, and by bioaccumulation through the food chain. The highest exposures occurred in occupational cohorts through inhalation or skin absorption in work environments. These cohorts can therefore provide important information on health risk from exposure to PCBs in the general population. To provide comprehensive evidence on cancer risk from PCB exposure, we have thus reviewed the epidemiological studies on workers occupationally exposed to PCBs. Overall, no excess for all cancer mortality was observed in the six studies providing information (573 cancer deaths versus 630.4 expected, corresponding to a standardized mortality ratio (SMR) of 91). Among neoplasms potentially related to PCB exposure, there were 12 deaths from liver cancer compared with 9.5 expected (SMR=126). No excess was found for cancers of the breast (40 observed versus 47.4 expected, SMR=84) and of the lymphatic and haematopoietic system (51 observed versus 53.2 expected, SMR=96). Therefore, studies on occupational exposure to PCBs do not show any excess in all cancer mortality, or in mortality for specific cancer sites of interest.

Persistent organic pollutants in food: public health implications.

Persistent organic pollutants are a heterogeneous group of chemicals sharing a number a common properties, including long term persistence and diffusion in the environment, and bioaccumulation through the food chain. Animal experiments and epidemiological studies suggest that the most sensitive adverse effects, such as disturbances on metabolism, development, and reproductive system, may occur in the range of current human exposure. Although the potential cancer risk of persistent organic pollutants remains undefined, the implementation of actions to reduce the exposure to these substances, which mainly occurs through the diet, is important.

Relative potency values derived from hepatic vitamin A reduction in male and female Sprague-Dawley rats following subchronic dietary exposure to individual polychlorinated dibenzo-p-dioxin and dibenzofuran congeners and a mixture thereof.

This study investigated the potency of individual polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) to reduce hepatic vitamin A in the rat. Dose-response relationships were determined following long-term dietary exposure to 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,4,7, 8-pentachlorodibenzofuran, 1,2,3,4,8-pentachlorodibenzofuran, 1,2,3, 7,8-pentachlorodibenzofuran, 1,2,3,6,7,8-hexachlorodibenzofuran, 1,2, 3,7,8-pentachlorodibenzo-p-dioxin, octachlorodibenzo-p-dioxin, octachlorodibenzofuran, or mixtures of some of these congeners. The aim was to estimate vitamin A-related relative potency (REP) values for each congener in relation to that of TCDD and to investigate if these values were in accordance with REP values estimated for the subchronic toxicity observed in the same study. An additional aim was to investigate if the effect on hepatic vitamin A levels was additive compared to the effect of the individual congeners. The obtained results demonstrate that hepatic vitamin A reduction occurs as a consequence of long-term low-level exposure to 2,3,7, 8-substituted but not to non-2,3,7,8-substituted congeners. Female rats were slightly more responsive to this effect as judged from the lower EC50 values for all the congeners in this sex. The vitamin A-related REP values were similar for female and male rats and were in good agreement with the estimated REP values for subchronic toxicity in the same animals. The vitamin A effect of the individual congeners in the mixture tended to be somewhat less than pure additive for male rats and very close to pure additive for female rats. In conclusion, the presented data show that reduction of hepatic vitamin A is a sensitive marker of an altered retinoid homeostasis following long-term low-dose exposure to dioxin-like compounds, which essentially conforms to their assumed additive mechanism of action.

Inter-laboratory validation of solid-phase microextraction for the determination of triazine herbicides and their degradation products at ng/l level in water samples.

The accuracy and precision of solid-phase microextraction (SPME) were validated in an inter-laboratory study including ten laboratories for the analysis of triazine herbicides and their metabolites at ng/l level in aqueous samples. The SPME conditions were optimised in order to obtain maximum sensitivity. Especially, salt addition and choice of the SPME fibre coated with Carbowax-divinylbenzene increased the sensitivity. The average detection limits were in the range from 4 to 24 ng/l for the triazine herbicides, and 20 and 40 ng/l for desisopropylatrazine and desethylatrazine, respectively. The average r2 values of the calibration curves were above 0.99 for all of the analytes. The statistical data treatment was performed in accordance with the International Standardisation Organisation (ISO) standard 5725. Relative repeatability standard deviations between 6 and 14% and relative reproducibility standard deviations between 10 and 17% were found. The determined concentrations of the reference sample compared well to the "true" values, thus proving the good accuracy of the method. It is concluded that SPME is a reliable technique for the quantitative analysis of water samples containing triazine herbicides in concentrations around the European limit of 100 ng/l for individual pesticides in drinking water.

Industrial pollutants in ground waters from northern Milan.

Ground water samples from an industrialised area near Milan were analysed by gas chromatography-mass spectrometry (GC-MS) to identify the main pollutants and to quantify two classes of chemicals: polychloro-1,3-butadienes (PCBD) and some aromatic amines. The water contained several halogenated aromatic and aliphatic compounds and heavy contamination due to PCBD, probably arising from contaminated land where a disused chemical plant is located. All the samples contained low levels of aromatic amines indicating a diffuse contamination probably arising from different sources.