Environmental contaminants and food safety

Transcription

1 Environmental contaminants and food safety Agneta Oskarsson Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala Sweden 26 th NKVet Symposium Environmental Contaminants and Animal Health, October 6-7, 2011, Helsinki

2 Food safety a topic of high concern (2009) Mats-Eric Nilsson: The Secret Cook, Genuin Stuff and Death in the Pot (2007, 2008, 2010)

3 Outline & acknowledgements Food risk perception Bisphenol A Mixtures Thanks to Åsa Ohlsson, Erik Ullerås, Christer Jansson, Nina Cedergreen

4 Risk perception in EU Eurobarometer 2005 and countries, persons Sweden persons Face-to-face interviews Link to report: (EU 168 pages)

5 Eurobarometer 2010

6 Eurobarometer 2010

7 Eurobarometer 2010

8 Sweden vs EU Eurobarometer 2010

9 Eurobarometer 2010

10 Eurobarometer 2010

11 Conclusion from EU barometer Public concerns about chemical residues in food is very high Lower concern about food poisoning and diet related diseases Sweden and Finland top concern is about animal welfare Risk communication from trusted person/organizations is needed

12 Bisphenol Bisphenol A High-production-volume chemical Used in polycarbonate plastics and epoxy resin liners in cans and water pipes Migration from food and beverage packaging Endocrine disruptor Effects on reproduction, central nervous system, cardiovascular diseases, diabetes, cancer Controversy about low-dose effects

13 Exposure from food packaging Study by Rudel et al, Environ Hlth Perspect, July 2011 BPA in urine was reduced by 66% when diet was changed into nonpackaged food

14 Maternal bisphenol A decreases attractiveness of male offspring PNAS July 12, 2011: Jasarevic et al ( ) Abstract: Both BPA-exposed and control females preferred control males to BPA-exposed males. Our demonstration that developmental exposure to BPA compromises cognitive abilities and behaviors essential for males to reproduce successfully has broad implications for other species, including our own. Thus, sexually selected traits might provide useful biomarkers to assess risk of environmental contamination in animal and human populations.

15 THE ADRENAL AS A TARGET OF TOXICITY Adrenal > testicle > thyroid > ovary > pancreas > pituitary > parathyroid (from regulatory toxicity studies) High blood flow High lipid content accumulation of lipophilic substances CYP enzymes metabolic activation Adrenotoxicants / Endocrine disruptors in vivo / in vitro Adrenal gland Capsule Zona glomerulosa Zona fasciculata Capillary Zona reticularis Cortex Medulla

16 Cholesterol StAR Steroidogenic pathways in adrenal cortex/h295r cells CYP11A1 Pregnenolone CYP17A1 a 17 -OH-Pregnenolone CYP17A1 b Dehydroepiandrosterone 3bHSD2 3bHSD2 3bHSD2 Progesterone CYP17A1 a 17 -OH-Progesterone Androstenedione CYP21A2 CYP21A2 CYP19 17bHSD 11-Deoxycorticosterone 11-Deoxycortisol Oestrone Testosterone CYP11B1/CY P11B2 CYP11B1 17bHSD CYP19 Corticosterone Cortisol Oestradiol CYP11B2 Aldosterone

17 Material & Methods Human adrenocortical cell line, H295R Cells were treated with BPA, mm, for 24 h Determination of cell proliferation Analysis of medium by multi-lc-ms/ms, ELISA and RIA Hormones Intermediate steroids Enzyme activities Analysis of steroidogenic gene expressions in cells by quantitative RT-PCR

18 Conclusions BPA BPA disrupts steroidogenesis with testosterone and cortisol as sensitive targets The effects are mediated by inhibition of CYP17 and CYP21 These effects, demonstrated in vitro, should be further investigated in vivo

19 Mixtures Chemical mixtures a great scientific challenge Food itself is a chemical mixture Plus contaminants Prediction models Concentration addition Independant action Tested in the H295R cell model

20 Cortisol secretion (in % of vehicle control) Results imidazoles - cortisol Dose-dependent inhibition of cortisol Similar individual EC 50 EC 50 of mixture similar to individual imidazoles Both CA and IA models excellently predicted the effect of the imidazole mixture Prochloraz Ketoconazole Imazalil Individual Mixture imidazole PKI PRO IA KETO CAIMAZ Concentration Imidazole (µm) (µm) Ohlsson et al, Toxicology, 275,21-28, 2010

21 Aldosterone secretion (in % of vehicle control) Results imidazoles - aldosterone Prochloraz Ketoconazole Imazalil Individual Mixture imidazole PKI PRO mia KETO mca IMAZ Biphasic patterns Prochloraz Ketoconazole Modification of CA and IA models needed Modified CA predicted the effect quite well Modified IA failed Concentration Imidazole (µm) (µm) Ohlsson et al, Toxicology, 275,21-28, 2010

22 Hormone secretion (in % of vehicle control) Hormone secretion (in % of vehicle control) Results flavonoids: daidzein, genistein and apigenin (A) (C) Cortisol Testosterone DGADAID 120 IA GENI CA API DGA IA CA DAID GENI API (B) Aldosterone (D) Oestradiol Single Total flavonoid (µm) DAID DGA GENI IA API CA Single Total flavonoid (µm) DGA IA CA DAID GENI API Ohlsson et al, Fd Chem Toxicol, 48, , 2010

23 Conclusion mixtures The H295R cell line is a good model for mixture effects on steroidogenesis Additive effects were demonstrated for imidazoles and flavonoids Mathematical prediction models are valuable tools in the assessment of mixture effects The modified concentration addition model require further assessment to evaluate its potential to predict biphasic effects

24 Thank you for your attention!