We think you have liked this presentation. If you wish to download it, please recommend it to your friends in any social system. Share buttons are a little bit lower. Thank you!
Presentation is loading. Please wait.
Published byPenelope Lacewell
Modified about 1 year ago
© FSANZ 2002
© FSANZ 2002 FUNCTIONS OF FSANZ FSANZ is a partnership between the Australian Commonwealth, State and Territory and New Zealand governments - an independent, expert body. Responsible for developing, varying and reviewing standards for food available in Australia and New Zealand and for a range of other functions including coordinating national food surveillance systems, assessing policies about imported food and developing codes of practice with industry.
© FSANZ 2002 Toxicology of acrylamide Dr Paul Brent/Dr Glenn Stanley FSANZ MARCH 2003
© FSANZ 2002 Acrylamide FSANZ is currently undertaking a review of the toxicology of acrylamide: 1.To determine whether acrylamide is a possible human carcinogen 2.To ascertain levels of acrylamide in food in Australia and New Zealand 3.If possible to establish a threshold for carcinogenicity 4.To establish risk management options for regulation of acrylamide in food if necessary
© FSANZ 2002 Acrylamide Toxicological studies available: Absorption, distribution, metabolism, excretion Acute and repeat dose Mutagenicity/genotoxicity Developmental and reproductive toxicity Carcinogenicity Epidemiological (human)
© FSANZ 2002 Toxicological profile ( Absorption, distribution, metabolism, excretion) Animals-Incomplete information available Rapid and complete absorption by oral, inhalation and dermal routes in a range of species Rapid distribution to a range of tissues and organs Accumulation in liver, kidney, testes, epididymis, skin and red blood cells Metabolised to glycidamide 60% dose excreted in urine in 24 h Information on bioavailability from foods as consumed needed
© FSANZ 2002 Toxicological profile ( Absorption, distribution, metabolism, excretion) Humans Limited information-mainly from accidental exposure Rapid and extensive absorption by oral route Haemoglobin adducts in blood samples via inhalation and dermal routes
© FSANZ 2002 Acute and repeat dose studies Oral LD 50 in rats, mice, guinea pigs and rabbits mg/kg bw Skin and eye irritant and skin sensitization Main effect non-lethal reversible neurotoxicity (peripheral nerves) Humans-acute poisoning at 375 mg/kg leading to hepatic effects and peripheral neuropathy PNS and CNS effects following repeated exposure in animals and humans. NOAELs and LOAELs established for animals from repeat-dose studies but difficult to characterise for humans
© FSANZ 2002 Developmental and reproduction studies Resorptions, decreased birth weights and bodyweight gain, decreased litter size, tibial and optic nerve degeneration in neonates. Parental effects-ataxia, abnormal gait, peripheral neuropathy, decreased litters/dam, increased pre- implantation loss, degeneration testicular epithelia, increased incidence sperm head abnormalities. A review of the available developmental toxicity data suggested that the LOEL was 20 mg/kg bw/day; no NOAEL could be established (Dearfield, 1998).
© FSANZ 2002 Genotoxicity In vitro Gene mutation assays-negative in bacterial assays (Ames test); however, metabolite glycidamide +ve; Mammalian and DNA tests generally negative or equivocal (CHO and mouse lymphoma cells-equivocal) but some positive (mouse lymphoma). Mutations in post-meiotic stages spermatogenesis. Chromosomal assays-aberrations and mitotic disruption in mammalian cell (in vitro CHO cells and lines), polyploidy and spindle disturbances. UDS negative for rat hepatocytes and +ve for human mammary cultures.
© FSANZ 2002 Genotoxicity In vivo Aberrations in bone marrow, spermatocytes, peripheral blood reticulocytes, spleen lymphocytes and spermatids UDS in rat and mouse spermatocytes +ve Dominant lethal +ve
© FSANZ 2002 Carcinogenicity Johnson et al (1986) 2-year study Fischer (F-344) rats receiving 0, 0.01, 0.1, 0.5 or 2 mg/kg bw/day. At doses of 2.0 mg/kg bw/day statistically increased incidences of mostly benign tumours of the mammary gland (fibroademonas), thyroid gland (adenomas), oral tissue (papilomas), clitoral gland (adenomas), pituitary gland (adenomas) and uterus (adenocarcinomas) in females. A non-statistical increase in incidence of CNS tumours (astrocytomas of the brain and spinal cord) were also reported in male and female rats at high dose. Statistically significant incidences of testicular mesotheliomas, at doses of 0.5 or 2.0 mg/kg bw/day and adrenal pheochromocytomas and thyroid adenomas in males at 2 mg/kg bw/day only) were observed.  Not statistically significant in females
© FSANZ 2002 Carcinogenicity (Continued) Friedman et al (1995)-male and female F-344 rats received doses of approximately 0, 0.1, 0.5 or 2.0 mg/kg bw/day and 0, 1.0 or 3.0 mg/kg bw/day acrylamide in drinking water, respectively. Study did not repeat some of the tumours noted in the earlier study (Johnson et al., 1986) (CNS glial neoplasms, papillomas of the oral cavity, adenomas of the clitoral gland, and uterine adenocarcinomas) at a similar dose range and in an identical rat species, although it did confirm mesotheliomas of the testis and benign tumours of the mammary and thyroid glands.
© FSANZ 2002 FSANZ evaluation of results of both carcinogenicity studies Mammary gland fibroadenomas incidence 28 to 38% at high dose (2-3 mg/kg bw/day) compared to historical control range of 2-44%; Testicular mesotheliomas incidence 16-18% compared to historical control range of 2-6% at high dose (2 mg/kg bw/day); Thyroid adenoma incidence 12-16% in males and 16% in females compared to historical control range of 0-5% males and 0-4% females at high dose (2-3 mg/kg bw/day); Uterine adenocarcinoma incidence of 8% at 2 mg/kg bw/day compared to historical control range of 0-2.5%. Adrenal pheochromocytoma incidences of 17% in males at 2 mg/kg bw/day compared to historical control range 1-14%.
© FSANZ 2002 Carcinogenicity (humans) 3 cohort studies (Sobel et al 1986; Collins et al, 1989; Marsh et al 1999) over years demonstrated no epidemiological evidence of a causal relationship between exposure to acrylamide and mortality Recent study (Mucci et al, 2003) assessed the diets of 987 cancer patients (591 with cancer of the large bowel, 263 with bladder and 133 with kidney cancer) and compared to 538 healthy control individuals. Found lack of association between acrylamide and cancer in those subjects consuming moderate ( g/kg) or high levels ( g/kg) of acrylamide in 14 different food types.
© FSANZ 2002 Conclusions to date from FSANZ review Mechanism (s) of carcinogenicity unresolved Genotoxicity tests suggest that acrylamide is a genotoxic carcinogen in vivo Carcinogenicity assays in animals suggest increased tumour incidence primarily in hormonal tissues such as adrenal, thyroid, mammary gland, uterus and testes. Majority of tumours benign
© FSANZ 2002 Conclusions to date from FSANZ review Anomalies: Lack of a dose-response relationship and NO time-to tumour data available; Only 2 tumours of significance to humans: Testicular mesotheliomas with an incidence level (16-18%) compared to historical control values for the Fischer rat strain (2-6%); Uterine adenocarcinoma incidences were increased in high-dose groups (Johnson et al, 1986), appear to be uncommon lesions in F-344 rats, not found in Freidman et al (1995) study and histological basis for these tumours is unknown.  This appears as a rare tumour in humans but is quite common in the Fischer strain of rat. 
© FSANZ 2002 Conclusions to date from FSANZ review The lack of consistency in reported tumours suggests that further studies are still needed to be performed in a different rat strain or different species such as the mouse or dog to help elucidate the significance of the tumours reported in the two studies to date. The epidemiological cohort studies done in humans previously exposed to acrylamide and tracked over a prolonged period failed to demonstrate any evidence of acrylamide-induced tumorigenicity or carcinogenicity. Most recent epidemiological study should be interpreted with caution due to: (1) Swedish group selected may not represent populations in other countries; (2) Limited range tumours selected; (3) Case-control study may not have enough power to assess cause and effect compared to cohort studies.
© FSANZ 2002 Copyright © Food Standards Australia New Zealand This work is copyright. You may download, display, print and reproduce this material in unaltered form only (retaining this notice) for your personal, non- commercial use or use within your organisation. Apart from any other use as permitted under the Copyright Act 1968, all other rights are reserved. Requests for further authorisation should be directed to
Incorporating Historical Control Data when Comparing Tumor Incidence Rates in Rodent Cancer Bioassay Shyamal D. Peddada Biostatistics Branch National Inst.
Endocrine-active pesticides: risk to human health. Hans Muilerman, PAN Europe
Group 5: Historical control data Follow-up of 2005 IWGT where the use of historical control data in interpretation of in vitro results was identified as.
Fundamentals of Genetic Toxicology in the Pharmaceutical Industry Prepared by: David Amacher, Ph.D, DABT
BPA characteristics: used for polymerization to form polycarbonate plastic Diagram depicting hydrolysis of the ester bond linking BPA molecules to form.
Pesticides and endocrine disruption Hans Muilerman, PAN Europe
Fluoride Arwa Owais. Fluoride: Human Health and Caries Prevention Fluoride ranks as a primary influence in better oral health because it demonstrated.
Radiation Long Term Effects II. Substantial animal data are available to describe fairly completely the effects of relatively high doses of radiation.
FALSE SCIENCE. Plant breeding Traditional breeding is unpredictable. The genes are mixed in a random fashion. Genetic modification is a precise technique.
Briefing for Interagency Review June 4, 2012 Draft Proposal for the Particulate Matter (PM) National Ambient Air Quality Standards (NAAQS) Washington,
Investigation of an Epidemic PRESENTER- DR GAURIJ HOOD MODERATOR- DR RANJAN SOLANKI.
Pump head syndrome. The Heart Valves 1. What is the function of the heart? To pump blood around the body so the cells can receive oxygen and food and.
Fluoride and the Endocrine System 2nd Citizens Conference on Fluoride St. Lawrence University July 29, 2006 Kathleen M. Thiessen, Ph.D. SENES Oak Ridge,
Practical Laboratory Testing for the Presence of Neurotoxins with Evidence-Based Treatment Protocols - Mark Schauss, MBA, DB Copyright 2008 Crayhon Research.
Group 6 Follow-up of in vivo positive results Follow-up of 2005 IWGT and subsequent work done by HESI IVGT on follow-up of in vitro positive results. Takes.
ENDOCRINE DISRUPTION DOES THIS POSE SPECIAL DIFFICULTIES WHEN ASSESSING RISK? Sue Barlow Independent Consultant in Toxicology.
Copyright © by Holt, Rinehart and Winston. All rights reserved. ResourcesChapter menu To View the presentation as a slideshow with effects select “View”
Training Manual on Risk Assessment of Living Modified Organisms in the context of the Cartagena Protocol on Biosafety (aligned with the Roadmap for Risk.
What are you most scared of? Shark attack Motorcycling Snakebite Smoking Driving Airplane crash.
1 The Role of Bioavailability in Pharmaceutical Product Development Alwyn Pidgen November 2012.
1. Competency BT10.00 Analyze Biomedical Research. Objective BT10.01 Discuss Biomedical Research 2.
GM FOOD/FEED: GAPS IN RISK- ASSOCIATED RESEARCH THAT NEED TO BE FILLED ARPAD PUSZTAI and SUSAN BARDOCZ.
© Boardworks Ltd of 48. © Boardworks Ltd of 48.
Basic Principles of Pharmacology Prof. Suheil Zmeili Faculty of Medicine Department of Pharmacology University of Jordan.
Germs ( Microbes ) Viruses, Bacteria, and Fungi What is a germ? The term 'germ' actually refers to any micro organism, especially those micro organisms.
Volume C: Addiction Medications and Special Populations Volume C: Addiction Medications and Special Populations Treatnet Training Volume C: Module 1 –
AMINO ACID Amino acids are critical to life, and have many functions in metabolism. Amino acids are organic compounds that combine to form proteins. Our.
June 4, 2012 Human Reproductive Health NURS 330. Abortion Spontaneous abortion – aka miscarriage – Loss of baby before 20 weeks of pregnancy Induced abortion.
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlikeLicense. Your use of this material constitutes acceptance of that license.
Integrating the care of NCD into PHC ECOSOC/UNESCWA/WHO Doha, May 10 th 2009 Nabil M Kronfol MD, DrPH.
© 2016 SlidePlayer.com Inc. All rights reserved.