Assessment and validation of US EPA's OncoLogic® expert system and analysis of its modulating factors for structural alerts.

OncoLogic® is a software program able to screen chemical compounds for toxicological effects. The software predicts the potential carcinogenicity of chemicals by applying rules of structure activity relationship (SAR) analysis. To validate the predictivity of OncoLogic® (Version 7.0), 123 compounds tested with the long-term carcinogenicity bioassay on rodents were extracted from the ISSCAN database and were analyzed. The concordance between the OncoLogic® SAR analysis and the bioassay results was high. To better understand the strength of the SAR science in OncoLogic®, we investigated the influence of a select group of modulating factors on the predictions by the structural alerts.

PCDD/F and PCB in human serum of differently exposed population groups of an Italian city.

A chemical plant located in Brescia, an industrial city in North-Western Italy, produced polychlorobiphenyls (PCBs) during a 30-50 year period, causing widespread pollution of the surrounding agricultural area. This area contains several small farms, which principally produce veal meat for private consumption of the farmers' families. The pollution went undiscovered for many years, during which period contaminated food was regularly consumed. This paper reports the polychlorodibenzodioxin (PCDD), polychlorodibenzofuran (PCDF) and PCB levels of a serum sample pooled from the consumers of contaminated food, compared to six population groups of the city of Brescia. Four of these groups were selected in order to represent, respectively, the local general population and the residents of three zones of the polluted area, while the last two groups represented, respectively, the present and the former workers of the plant. One human milk sample from one of the consumers of contaminated food was also analyzed. Results show that the consumers of the contaminated food and the former workers of the plant display considerably higher levels than all other groups. The levels of general population and of all other groups were generally similar both to each other and to the range of literature values for unexposed populations. The respective contribution of PCDDs, PCDFs, mono-ortho and non-ortho PCBs (dioxin-like PCBs) to (Toxicity Equivalents) TEQ of the population groups of this study were also compared to literature data: the two groups with a high contamination level, together with the human milk sample, displayed a higher incidence of mono-ortho PCBs and a lower contribution of PCDD, possibly correlated with the source of contamination.

A study on PCB, PCDD/PCDF industrial contamination in a mixed urban-agricultural area significantly affecting the food chain and the human exposure. Part I: soil and feed.

This study deals with a PCB, PCDD and PCDF contamination in Brescia, a city in the North-West of Italy, affecting an area with about 11000 inhabitants. The area is close to an industrial plant that produced, in total, some 31,000 ton of PCB. A relevant part of the polluted area is agricultural soil, where cattle were fed with polluted forage and farmers were consuming their own products, so that contamination led eventually to human exposure. Total levels of PCDD/Fs varied from 8 to 592 pgTE(WHO)/g for soil samples and when the dioxin-like PCBs (dl-PCBs) are included, the levels varied from 14.6 to 1033.7 pgTE(WHO)/g. In several cases, the legal limit was exceeded by more than one order of magnitude, with the highest contamination in some agricultural areas and in the surrounding zones. For the forage samples, total levels of PCDD/Fs varied from 0.29 to 2.04 pgTE(WHO)/g and, when dl-PCBs are included, this range increased from 2.04 to 4.75 pgTE(WHO)/g. PCB contamination of the forage through vapor condensation seemed to be relevant. The toxic contribution of dl-PCBs is always relevant and must be considered for risk management. The main component of the contamination source is probably a heavy PCB mixture, such as Aroclor 1262. The study dealt generally with the contamination transfer of PCBs, PCDDs and PCDFs from soil up to humans across the food chain. Results on soils and forages are shown, while measurements concerning the contamination of the animals fed with contaminated forage, and the exposure of the farmers (through human serum analyses), as compared to general population, will be reported in a dedicated paper.

PCB, PCDD and PCDF contamination of food of animal origin as the effect of soil pollution and the cause of human exposure in Brescia.

In Brescia a PCB production plant polluted soil and forage of the surrounding fields and caused a significant contamination of meat and milk of the cattle fed with local forage. This in turn induced elevated blood levels of PCDDs, PCDFs and PCBs in the consumers. The contamination levels and profiles measured in the perirenal fat, in the liver and in the milk of the overall 28 contaminated bovines are reported. TEQ levels varied from 30 to 81 pg WHO(2005)-TEQ g(-1) (38-103 pg WHO(1997)-TEQ) for perirenal fat, from 107 to 138 pg WHO(2005)-TEQ g(-1) fat (128-168 pg WHO(1997)-TEQ) for liver and from 45 to 50 pg WHO(2005)-TEQg(-1) fat (56-65pg WHO(1997)-TEQ) for milk; all these values are roughly tenfold higher than the European limits. Non-ortho dioxin-like (dl)PCBs are by far the largest contributors to TEQ and PCDF contribution also largely prevail over PCDD's; both these features are also present in both the contaminated forages and in the serum of consumers of contaminated food. The indicator PCB levels are in the following ranges: 226-664 ng g(-1) for perirenal fat; 929-1822 ng g(-1) fat for liver; 183-477 ng g(-1) fat for milk; their level is about 100 times higher than the regional background. The liver samples displayed an overall TEQ several times higher than the perirenal fat from either the same animal or the same pool of animals; the increase in liver concentration was significantly higher for PCDD and PCDF congeners than for dlPCBs, and it was maximum for OCCD.

TEQ(S) and body burden for PCDDs, PCDFs, and dioxin-like PCBs in human adipose tissue.

Polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), mono-ortho and non-ortho polychlorinated biphenyls (dioxin-like PCBs) were determined in samples of human fat tissue from nine Italian obese patients. The toxicity equivalent (TEQ) values ranged from 9 to 25 pg TEQ g(-1) lipid (WHO-TEF values, 2005 [Van den Berg, M., Birnbaum, L.S., Denison, M., De Vito, M., Farland, W., Feeley, M., Fiedler, H., Hakansson, H., Hanberg, A., Haws, L., Rose, M., Safe, S., Schrenk, D., Tohyama, C., Tritscher, A., Tuomisto, J., Tysklind, M., Walker, N., Peterson, R.E., 2006. The 2005 World Health Organization reevaluation of human and mammalian Toxic Equivalency Factors for dioxins and dioxin-like compounds. Toxicol. Sci. 93, 223-241]), the contribution of dioxin-like PCBs was more than 30% of the total TEQ values. The obese body burdens varied from 6 to 11 ng TEQ kg(-1) body weight (BW), exceeding the estimated steady-state body burden 5 ng TEQ kg(-1) BW, based on lipid adjusted serum concentrations from several populations in the mid-1990s, calculated in the risk assessment US EPA document.