^17th Global Toxicology and Risk Assessment Conference October 22-24, 2018 Budapest, Hungary

Biography:

Yong Joo Chung has his education in Food Science and Toxicology and experience in allergen and chemical risk assessment. He involves in safety assessment for new or existing ingredients for human and for pets. While he works on safety assessment, he had an opportunity in developing a tool for managing contaminants in raw materials, which influences most of Nestle business. The model is based on global consumption, extensive analytical data, and HBGVs to protect consumers from chemical contaminants. This approach covers all food categories except infant foods and pet foods. He is currently focusing on contaminant management and alternative method development for risk assessment

Abstract:

Management of contaminants in food raw materials is a key for producing safe foods. Complying with Health based-guidance values makes sure consumers being protected from contaminants of concern. This presentation will introduce a globally valid chemical risk assessment tool that provides the user with a priority rating in terms of which chemicals are important to manage in raw materials based on global dietary information. The process involves the use of decision trees that enable the determination of risk (or “likelihood to cause harm”) and severity using objective and transparent selection criteria. Thereafter, severity and risk are positioned in an HACCP-like matrix, informing on the prioritization level of each combination of chemical hazard and raw material. The developed model is intended to be adequately protective for consumer's health, as it considers a conservative food intake scenario, as well as various sources of contaminant exposure. The model's design is flexible and can easily be adapted to the needs of different food product categories and scenarios. The model was tested using several examples, the results of which are consistent with existing data in the literature. Case studies including heavy metal and mycotoxin will be presented to illustrate the feasibility of the approach

Biography:

Rana Jaffer is an Emergency Medicine Consultant, working at Hamad Medical Corporation in Doha, Qatar. She has completed her Medical School from Aden University, Yemen, followed by Residency in Emergency Medicine from Arab Board of Medical Specialties. She is a Member of the Royal College of Emergency Medicine, UK. Further, she has completed her Post-graduate Diploma in Toxicology from Cardiff University, UK. She is an active Member of the Toxicology Team at her hospital besides being a Faculty Member at Emergency Medicine Residency Teaching program at Hamad Hospital and at Qatar University. Her professional focus has always been to teach Emergency Medicine and Toxicology to residency students and improve their skills for better patient care. She has special interest in talking about khat abuse (Catha edulis) which is a common practice in the Middle-East and North Africa. She thinks a conference is a good media for sharing knowledge and cultures from different parts of the world

Abstract:

Substance abuse is a tragedy every society and health system face in the world. Forms and patterns of abuse vary from one place to another. The khat (Catha edulis) shrub is cultivated in the Arabian Peninsula, and North Africa. The citizens of this region have been carrying the tradition of chewing khat leaves since 15^th century and this culture has been passed on from generation to generation. Khat sale is a source of income to these countries. But it has its own pros and cons on mankind, society and environment. The chemical structure of khat is made up of cathinones and cathine. On one hand Yemen, Ethiopia, Kenya, Somalia and Sudan are preoccupied in khat abuse, the western world has the synthetic cathinones (bath salts) hitting their markets with all sorts of exotic colors, shapes and shades. Though khat consumption and abuse might not be a common practice in the western countries but spreading and sharing knowledge would certainly enrich our skills as physicians for providing efficient patient care

Biography:

Dániel József Kócsó is a PhD student at Pécs University, Hungary. Since April 2015 has been a member of MTA-KE mycotoxins in the food chain research  team and he works as assistant research fellow

Abstract:

The worldwide contamination of foods and feeds with mycotoxins is a significant problem. Different apoptotic and pathological changes attributable to the presence of mycotoxins trigger cytoprotective molecular processes associated with the increased production of heat shock proteins (Hsp’s). Their altered expression can be an early marker of cytotoxic effects confirmed by some former author in which among others on the basis of the Hsp expression depending on the type of mycotoxin different oxidative levels can be associated with. In our former establishing in vivo experiment rats were exposed to diet containing FB1 in a dose of 50 mg/kg for 5 days. Western blot analysis of the lungs and kidney demonstrated a substantial (1.4-fold and 1.8-fold, respectively) increase in Hsp70 expression referring to changes in the intracellular mechanisms. In the following to test the acute effects of combined, naturally co-occurring fusariotoxins, a 5-day rat study was performed.  Mycotoxin treatment was devised by intraperitoneal injection: FB1 (F): 9 µg/animal/day (approx. 30 µg/kg bw/day), DON (D): 16.5 µg/animal/day (approx. 55 µg/kg bw/day) and ZEN (Z): 12.75 µg/animal/day (approx. 42.5 µg/kg bw/day). From the examined organs the lungs and liver didn’t show any increase in the expression of Hsp70 rather it seems that the single and combined  treatments lowered the production of Hsp’s. Regarding the lungs alterations were significant in the FB1, DON, ZEA, FB1+DON, FB1+ZEA and DON+ZEA groups compared to the control while as for the kidneys a mild but not significant elevation was detected. It can  be concluded that the  decrease of Hsp’s may be due to the presence of different inhibiting agents modulating the actual cytoprotective mechanisms. Changes in the kidneys are attributable to the differing sensitivity and molecular processes to the exposure of mycotoxins. Our present results need further examinations for getting a brighter picture about the mode of actions

Biography:

MSc Karolina Zajda is a PhD student in Department of Physiology and Toxicology of Reproduction , Jagiellonian University in Krakow. She is specialized in cancerogenic action of endocrine disruptor in ovarian cancer. She has graduated from Jagiellonian University in Krakow, Poland. She has authored 3 peer-reviewed articles in leading journals such as Toxicology, Cancer Genomics and Proteomics and Reproductive Toxicology. Member of The Polish Society for Reproductive Biology. Research topics focusing on the effects of different single and mixture of endocrine compounds in hormone dependent cancer

Abstract:

STUDY QUESTION: Does, dependent on structural characteristics, PAH mixture acts as endocrine disruptors in human granulosa cell.

WHAT IS KNOWN ALREADY: Effects of PAHs in reproductive tissues could reflect their multiple modes of action, like activation of aryl hydrocarbon receptor (AhR)-dependent metabolism, as well as, activation of estradiol receptor (ER) in ER-sensitive cells. Antiestrogenic activity of PAHs was observed in a yeast assay system, while estrogenic activity was found in hormone dependent, breast cancer MCF-7 cells. 

STUDY DESIGN, SIZE, DURATION: The analysis of the concentrations of 16 PAHs identified as priority pollutants by both the US Environmental Protection Agency and the European Commission, in maternal and cord blood showed similar content of these compounds in both.   It points to cross through placenta and indicate that exposure to PAHs during fetal life may contribute to abnormal ovarian function in adult.

To explore the mechanism of PAHs action we used HGrC1 (human no luteinized granulosa cell line) originally derived from mural granulosa cells, possess the characteristics of granulosa cells in early stage follicles. The cells were exposed for 24 and 48h on 2 mixture: M1 composed of all 16 PAH and M2 composed of five not classified as human carcinogens (naphthalene, phenantrene, anthracene, fluoranthene and pyrene) observed at the highest levels in maternal and cord blood. At the end of the culture, we examined estradiol level in medium by ELISA. FSH, AhR, AR, ER, CYP19 protein expression was measured by Western blot and cell proliferation by AlamarBlue assay. Additionally, estradiol level and cell proliferation were evaluated after AhR, AR and ER gene silencing. 

MAIN RESUTS: Both PAH mixtures had no effect on FSH protein expression. However, differences in the action on AhR, ER and AR was pronounced.  Mix 1 increased AhR and ER expression and was without effect on AR expression, while M2 increased both AR and ER expression and had no effect on AhR expression. Both mixture  had inhibitory  effect on basal and FSH-stimulated estradiol secretion however without effect on aromatase activity. In basal condition AhR gene silencing had no effect on  estradiol secretion while ER and AR gene silencing caused increase estradiol secretion. In cells exposed for mixture siAhR reversed inhibitory action of both mixture on basal and FSH stimulated estradiol secretion. After ER and AR gene silencing  still inhibitory effect on  estradiol secretion was noted. 

CONCLUSION: Independent on mixture composition both cross talk between AhR/ER and AhR/AR exist. We suggest that, in real life mixture, not only  compounds regarded as carcinogenic, but also till now not classified as cancerogenic, are responsible for the antiestrogenic  action of the mixture.

Biography:

Omeralfaroug Ali is a PhD Fellow at University of Kaposvar, Hungary. Since July 2017, he has been Member of MTA-KE Mycotoxins in the Food Chain Research Group and works on the assessment of fumonisin B1 exposure on the cellular membrane lipids

Abstract:

Due to the structural similarity between fumonisin B1 (FB1) and sphingolipids (essential substances for membrane composition), FB1 is able to disturb the sphingolipid metabolism. The aim of this study was to test the effects of oral administration of FB1 on the total fatty acid (FA) profile of phospholipids (PL) and triglycerides (TG) of weaned piglets. The 10 days in vivo experiment was performed on 14 animals (seven/group): control (FREE) and orally intoxicated (TOXIN) by 20 mg FB1/kg diet. Statistical differences were analyzed by SPSS using independent samples t-test with p-value < 0.1 as a level of significance. From results, the decrease in proportions of many saturated fatty acids (SFA) (C24:0 was the most apparent alteration) was a consequence of FB1 administration, as the total SFA of the kidney PL was low in TOXIN. Despite the decrement in proportions of omega-3 (ω-3) FAs (C22:6n3 was the most responsive FA), the total unsaturation (UFA) was high due to an increment in proportions of omega-6 (ω-6) FAs (C20:4n6 was the most responsive FA). Thus, has altered the overall ω-6: ω-3 ratio (increased), most clearly in the liver PL. However, total proportions of ω-6 and ω-3 of TG were not affected by the FB1 exposure but some of their classes were influenced. To assess the oxidative load, the MDA was measured. Interestingly, the MDA concentration was high in the liver of TOXIN. Thus, the liver was characterized by undergoing oxidative stress due to the FB1 exposure. It can be concluded that the 20 mg FB1/kg diet orally exposure for 10 days has altered the renal and hepatic lipid metabolism of piglets, especially the hepatic tissue and PL fraction (most alteration). Moreover, FB1 has induced lipid peroxidation in the liver but not in the kidney, at least under the exposure dose and period of this study

Biography:

Heon Kim has his expertise in Environmental Epidemiology and passion in finding new biological markers for environmental pollutants. He has performed environmental epidemic surveys on the health effects of chronic cadmium exposure in people who have been living near a closed copper refinery and have been following up those with high blood or urinary cadmium levels

Abstract:

Chronic exposure to cadmium (Cd) induces renal tubular damage and oxidative stress, but, limited data are available on the effect of copper (Cu) - zinc (Zn) imbalance on Cd induced toxicity. The purpose of this study was to assess the effects of environmental Cd exposure and Cu - Zn imbalance on renal tubular damage and oxidative stress in population living in a Cd polluted area. The subjects of this cross-sectional study were 979 adults, who were 30 years old or older, and had been living more than five years within 15 km of a closed copper refinery. We measured Cd concentrations in blood and urine and copper (Cu) and zinc (Zn) levels in serum. Urinary levels of β2-microglobulin (β2-MG) and N-acetyl-β-D-glucosaminidase (NAG) activity, as markers for renal tubule damage, and urinary concentration of Malondialdehyde (MDA), as an oxidative stress marker, were analyzed. The geometric mean concentrations of Cd in urine were 2.25 μg/g creatinine. Urinary Cd levels were positively correlated with urinary NAG activity, β2-MG and MDA levels, but not with serum Cu/Zn ratio (CZR). There was a significant correlation between serum Cu/Zn ratio and urinary MDA level. When stratified by urinary Cd level, urinary β2-MG level was strongly associated with serum CZR in low urinary Cd group (β=1.198, P=0.020), and with urinary Cd level in high urinary Cd group (β=1.061, P=0.001). After adjustment for covariates, serum Cu/Zn ratio was significantly associated with urinary MDA levels regardless of urinary Cd level. These findings indicate that imbalance in Cu and Zn is a determinant for oxidative stress and renal tubular damage in population chronically exposed to Cd, and that proper Zn supplementation is needed to prevent adverse health effects by Cd

Biography:

Yong-Dae Kim has his expertise in Environmental Epidemiology and passion in finding new biological markers for cadmium exposure. He has taught on Preventive Medicine and Biostatistics in College of Medicine, Chungbuk National University, Republic of Korea

Abstract:

Cadmium (Cd) is the most potent nephrotoxic heavy metal and chronic exposure to Cd increases the risk for chronic renal disease. However, the relationship between urinary Cd and estimated glomerular filtration rate (eGFR) has been controversial. This study was performed to evaluate the relationship between urinary Cd concentration and renal disease markers, such as eGFR, in a relatively large general population sample. Among the 1,086 volunteers who were enrolled in this study, 856 healthy volunteers who did not have kidney disease were included the final analysis. Urinary Cd, malondialdehyde (MDA) and N-acetyl-β-D-glucosaminidase (NAG) concentrations were measured, the creatinine-based eGFR was calculated and the relationships between these markers were subsequently analyzed. We found that the urinary NAG and MDA levels were significantly higher and the eGFR was significantly lower in the low Cd group (<2 µg/L) than in the high Cd group (>2 µg/L) in both men and women. Urinary Cd concentration without adjustment for creatinine had a positive correlation with urinary MDA levels and a negative correlation with eGFR. This relationship was relatively stronger in women than in men. This study showed that urinary Cd level was associated with decreased glomerular filtration rate (GFR) in the general population and oxidative stress was likely to act as an intermediator in this process. These results suggest that eGFR can be a very good indicator of kidney damage caused by Cd exposure in the general population. Additionally, this study suggests that the use of urinary Cd concentration without adjustment for urinary creatinine rather than the adjusted value may be appropriate in studies evaluating renal function based on Cd exposure

Biography:

Abstract:

Background

Mentha mozaffarianii, an endemic species from the Labiatae family, is used in Iranian traditional medicine. This study evaluated the acute and repeated oral toxicity of the Mentha mozaffarianii essential oil (MMEO) in rats and mice.

Methods

To assess the toxicity profile of the MMEO, we administered the essential oil to 48 rats and mice of both sexes by gavage in acute and repeated models. In acute toxicity, the animals were administered the MMEO (2000 mg/kg) and were monitored for 14 days. In the repeated toxicity, the MMEO was administered (100 mg/kg) daily for 4 weeks. On the 28th day, all the animals were scarified and blood and tissue samples were prepared. All the clinical, biochemical, and histopathological changes were assessed and compared with those in the controls.

Statistical significance was determined by one- and two-way analyses of variance, followed by the Tukey test using GraphPad Prism 6.

Results

In the acute test, there was no mortality; therefore, the oral LD₅₀ value determined in the mice and rats of both sexes was greater than 2000 mg/kg. In the repeated test, the animals received the MMEO and there was no mortality. In the biochemical analysis, there were significant increases in blood glucose, cholesterol, ALT, AST, ALP, and TSH in the female rats and also in BUN in the male rats. The histopathological studies revealed evidence of microscopic lesions in the liver, kidney, stomach, and small intestine tissues of the MMEO group.

Conclusion

The results indicated that the acute toxicity of the MMEO in the mice and rats was of a low order and it revealed slight tissue damage to several organs when given subchronically at a dose of 100 mg/kg

Biography:

Zu-yue SUN is the research director of National Evaluation Centre for the Toxicology of Fertility Regulating Drug; a laboratory has acquired the GLP certificate of CFDA (China Food And Drug Administration). 258 study projects being carried out in his laboratory, he has published more than 312 theses in china and abroad reputed journals.

Abstract:

Objective: The objective of this study was to determine the toxicokinetic profile of curdione in pregnant SD rats as well as the transference of curdione into the fetus through the placental barrier system using LC-MS/MS.

Methods: A sensitive analytical method for determining the plasma concentration of curdione was developed and applied in the determination of curdione in pregnant SD rats as a simulated model. Thirteen pregnant SD rats were treated with 7, 21 and 63 mg/kg curdione once daily from GD₆ to GD₁₅. Blood samples were collected at different time points on GD₆ and GD₁₅. Maternal plasma, placental plasma, placenta tissue, amniotic fluid and fetal tissue were collected for concentration analysis after all the animals were sacrificed following one repeated dose.

Results: The results indicated that Cmax, AUC(0-t) and AUC(0-∞) increased in a dose-dependent manner both on GD₆ and GD15. At 7 mg/kg group, the total serum clearance value on GD₁₅ was reduced to approximately 16.4% of that on GD6, and the volume of distribution was also significantly decreased (p<0.05). Curdione could be detected in the maternal plasma, placental plasma, placenta tissue, amniotic fluid and fetal tissue, and its concentration in the fetal tissue reached saturation at 21 mg/kg. Conclusion: It presents with the risk of toxic accumulation in the concomitant toxicokinetics of reproductive toxicity studies in SD rats and may affect the fetus via transference through the placental barrier system.

Biography:

Luo Yongwei has completed his PhD at the Department of Pharmacy, Fu Dan University, 2018. He is now working as a study director in National Evaluation Centre for the Toxicology of Fertility Regulating Drug, Shanghai, China; a laboratory has acquired the GLP certificate of CDA (China Drug Administration). He has shown great expertise in the area of pre-clinical toxicity evaluation of new drugs for nearly 10years, and has published a number of articles in reputed international journals

Abstract:

Miscarriage is a common obstetric disease, occurring in 15%–40% women of reproductive age. Various traditional Chinese medicines treating miscarriage have been widely used throughout the pregnancy race, which were defined as one category of the complementary and alternative medicines by the National Center for Complementary and Alternative Medicine. Thereby, the long term toxicology of these medicines and their impacts on liver is more and more concerned by clinical physicians and infertility couples. Zishen Yutai pill (ZYP) is one of the most commonly used Chinese medicines for miscarriage. The objective of this 39-week study was to investigate the potential long-term toxicity and hepatotoxicity of ZYP administered to beagle dogs at dose levels of 1.5, 3.0 and 6.0 g/kg bw/day by oral gavage and to determine reversibility of any findings after the 4-week recovery period. Physiological saline was used as control respectively. Clinical observation, mortality, body weight, blood pressure and electrocardiogram, clinical pathology, organ weights, histopathology, hormones, and traditional and potential hepatotoxicity biomarkers were detected and recorded. There were no mortality or toxic clinical symptoms and abnormalities in both sexes of beagle dogs except for the expected exaggerated pharmacological effects typically associated with female reproductive organs, which typically induced on endometrial thickening, dilated lactiferous ducts in mammary gland and vigorous-growth oocytes in ovary. No obvious ZYP-related hepatotoxicity was observed after 13 and 39 weeks of ZYP treatment. Based on these results, the no-observed-adverse-effect-level (NOAEL) of ZYP in dogs is higher than 6.0 g/kg when administered orally for 39 consecutive weeks. Therefore，this study has suggested that no drug-related toxicity was induced by ZYP administered up to 6.0g/kg/day to beagle dogs for 9 months. Since this dose is approximately 24 times as much as the clinical dose, it indicates a good safety margin of this product