Food Safety Screening:
Synthetic Glucocorticoids

Contract n°: QLK1-1999-00122
Total cost : 1,636,392
Co-Ordinator : Prof. Dr. Carlos Van Peteghem

The goal of this project is to develop and disseminate innovative methods for the detection of synthetic glucocorticoids in animal fluids and tissues.

Results and applications:

  1. a rapid, sensitive and high-throughput chemiluminescence immunoassay
  2. confirmatory and identification methods based on liquid chromatography coupled to mass spectrometry
  3. a reporter gene-based bioassay to replace animal testing for measuring the pharmacological potency of glucocorticoids and their metabolites or derivatives
  4. a proteome analysis assay to detect expression of endogenous glucocorticoid-responsive genes in liver or other tissues and identify markers for glucocorticoid exposure

Validation and standardisation of diagnostic PCR for the detection of food borne pathogens

Contract n°: QLK1-1999-00226
Total cost: 2,326,333
EC contribution: 1,607,220
Co-ordinator: Dr. Jeffrey Hoorfar

A project seeking to validate and standardise use of the polymerase chain reaction (PCR) to detect food-borne pathogens.

To facilitate its routine use for diagnostic purposes, participants in the new project are being asked to undertake a series of specific projects, including to construct a DNA sample library and primer databank, validate widely used thermocyclers and other automated equipment, and to develop uniform guidelines describing how tests should be conducted. Because much of the challenge in applying PCR to food-borne pathogens is technical, there is also a need to develop standardised training manuals and procedures for those who will conduct such tests.

Construction of miniaturised free flow electrophoresis (mFFE) systems incorporating dedicated sensors for real-time analysis of food contaminants

Contract n°: QLK1-1999-00343
Total cost: 1,192,111
EC contribution: 439,814
Co-ordinator: Dr. Pradip PATEL
Leatherhead International Ltd

It is the strategic objective of this project to test the practical feasibility of miniaturised free flow electrophoresis (mFFE) systems with downstream dedicated sensors for the real-time measurement of three selected analytes (e.g. aflatoxin, markers for recombinant bovine somatotrophin, rBST, and Listeria) as a tool to address selected problems of food safety.

Expected Results

Two (pre)prototype of miniaturised FFE (mFFE) systems; microfabricated and minifabricated FFE systems.

Measurement of the specified analytes using optical biosensor system from defined aqueous preparations and application data on real foodstuffs.

Development of (pre)prototype integrated mFFE-based sensor technology for estimation of at least one of the specified analytes from foodstuffs.

Comparative data between the new FFE-based measurement and the conventional techniques.

Cartridges with molecularly imprinted Recognition Elements for Antibiotic residues Monitoring in Milk (CREAM)

Contract n°: QLK1-1999-00902
Total cost: 1, 509, 577
EC contribution: 833, 217
Co-ordinator: Dr. Maria Kempe

To meet the need of alternative confirmatory methods and practical instrumentation for on-site monitoring and discrimination of b-lactam residues in milk, the main objective of this project is to develop and optimise a plug-in detection cartridge supporting a molecularly imprinted polymer assay.

Expected results

The concept of a cartridge supporting a molecularly imprinted polymer (MIA-cartridge) will be demonstrated. State-of-the-art replication techniques in plastics will ultimately be utilised to produce cheap and disposable cartridges. A portable instrumentation will be developed to enable screening tests to be performed at the farm and processing dairy with MIA-cartridge prototypes. Field trials will assess the validity of this analytical system.

Development, validation and application of stochastic modelling of human exposure to food chemicals and nutrients

Contract n°: QLK1-1999-00155
Total cost: 2,891,840
EC contribution:2,046,640
Co-ordinator: Professor Michael Gibney,

To develop a comprehensive set of mathematical algorithms, purpose built to take account of all the necessary components for stochastic modelling of a variety of food chemicals and to develop appropriate computer software.

Expected Results

The production of a software program purpose built for the stochastic modelling of food chemical intake.

The completion of a scientifically robust validation test of the software programme for its capacity to stochastically model food chemical intake.

The production of a set of practical guidelines for the appropriate use of stochastic modelling for food chemical intake studies.

Applications

The anticipated application of this new software and accompanying practical guidelines, is in the assessment of exposure to a range of food chemicals including food additives, pesticides and nutrients. This new technology is intended for use by regulatory authorities, industries, nutritionists and other research scientists.

Development of assays for the detection and prediction of co- and anti- mutagenic constituents in food with cells of human origin

Contract n°: QLK1-1999-00810

Total cost: 1,069,386

EC contribution: 898,019

Co-ordinator: Dr. Firouz Darroudi

The overall aim of the project is to investigate the effect of dietary constituents and contamination on the genotoxic effects of representatives of major groups of food derived carcinogens in cells of human origin. To obtain reliable information which of the food constituents may enhance or reduce the health risks of humans.

Techniques will be developed and applied using human derived liver cells that reflect the activation/ detoxification of genotoxic carcinogens better than other indicator cells that are currently being used. Therefore, have an increased predictive value for the identification of mutagens, co- and anti- mutagenic constituents of human foods.

Functional Food ingredients against Colon Cancer ó Development of a genomics and proteomics based screening assay

Contract n°: QLK1-1999-00706
Total cost: 2897119
EC contribution: 1587018
Co-ordinator: Dr. Ruud A. Woutersen

Two new technologies have recently become available which allow for a thorough assessment of changes in expression of all known genes (genomics) and proteins (proteomics) involved in (colorectal) carcinogenesis. The aim of the present project is to develop a bioassay, based on genomic and proteomic changes in colorectal cells, in order to identify food components specifically designed to prevent the development or progression of colorectal cancer.

Key action 4

Genetic mechanisms involving ultraviolet light in the development of cutaneous malignant melanoma

Contract no. QLK4-1999-01084
Co-ordinator: Prof. Robert Newbold

The principle measurable objectives of this project are:

  1. the isolation of key tumor suppressor genes involved in the various stages of human CMM ( cutaneous malignant melanoma) development and a detailed molecular description of their structural integrity in melanoma samples,
  2. development of animal models for CMM and their use to determine the relative efficacies of different wavelenghts of UV in melanomagenesis,
  3. development of human cell culture models for studying the cellular and genetic events involved in CMM induction,
  4. identification, in melanoma and premalignant naevi of molecular signatures of UV exposure in genes encoding elements of known tumor suppressive pathways,
  5. identification of heritable factors influencing melanoma susceptibility in a Syrian hamster model and in human population, and
  6. identification of molecular signatures of indirect (eg. oxygen radical) DNA damage by UV-A during the tumorigenic conversion of skin cells.

Risk assessment for occupational dermal exposure to chemicals

Contract no: QLK4-1999-01107
Co-ordinator: Dr Joop. J. Van Hemmen

Defects of the skin as barrier leads to increased uptake of chemicals that reach the skin by deposition or through contact with contaminated surfaces. Current methodologies for assessing these dermal exposures are, however, inadequate. The proposal aims to reduce acute and chronic ill–health through dermal contact with chemicals, developing two essential tools for management of dermal exposure and prevention of ill–health: a validated predictive model for estimating dermal exposure for use in risk assessment of single chemicals and a practical dermal exposure risk management tool for use by SMEs and others, for workplaces.

European prospective study of environment, allergy and the lung

Contract no : QLK4-1999-01237
Co-ordinator: Prof. Peter Burney

The proposed study is the nine year follow-up phase of a multicentre, prospective study of more than 10,000 young adults living in Europe. The proposed study has five overall objectives

  1. 1.To determine the incidence and prognosis of allergy, allergic disease and low lung function in adults living in Europe.
  2. To describe the distribution of exposure to known or suspected environmental risk factors associated with the incidence and prognosis of allergy, allergic disease and low lung function.
  3. To determine the risk attributable to chronic exposure to these environmental risk factors for the incidence and prognosis of allergy, allergic disease and low lung function.
  4. To identify subgroups within the population based on gender, prior disease status, bronchial responsiveness and genetic risk who may be more susceptible to these environmental risk factors and measure their excess risk.
  5. To establish a DNA bank taken from representative samples of the population that can be linked to health and environmental information.

Development of methods for predictive toxicity testing with reference to neurotoxic volatile chemicals

Contract no : QLK4-1999-01356
Co-ordinator : Ass. Prof. MD, PhD Sandra Ceccatelli

The project aims at developing in vitro models to improve predictive toxicity testing and mechanism- based risk assessment for volatile neurotoxic substances, with the ultimate goal of reducing, and possibly replacing, animal testing.

In contrast to other field of toxicology, the identification of end-points for neurotoxic effects has been progressing very slowly due to the complexity of the nervous system and the limited knowledge of the exact mechanism(s) of action of most neurotoxicants. This project should provide mechanism-based biomarkers that could improve risk assessment.

Genetic polymorphisms and biomonitoring of styrene

Contract no: QLK4-1999-01368
Co-ordinator: Dr Ari Hirvonen

The present project aims at the clarification of the potential role of the genetic polymorphisms in CYP2E1, EPHX, GSTM1, GSTP1 and GSTT1 genes in determining individual responses to styrene exposure. The blood samples of exposed subjects will be studied for adducts in DNA and blood proteins, and cytogenetic changes in peripheral lymphocytes. Cytogenetic alterations will be examined both by microscopic methods and new molecular genetic techniques. The exposure to styrene will also be assessed by personal air sampling and urine metabolite analysis.

Increasing incidence of human male reproductive health disorders in relation to environmental effects on growth- and sex-steroid induced alterations in programmed development

Contract no: QLK4-1999-01422
Co-ordinator: Prof. Dr med. Niels E. Skakkebaek

This proposal addresses the issues of declining male reproductive health and its causes. It will use standardised methods and a central European database :

Comprehensive risk analysis of dioxins: development of methodology to assess genetic susceptibility to developmental disturbances and cancer

Contract no: QLK4-1999-01446
Co-ordinator: Prof. Jouko Tuomisto

The objective is to set a scientifically defendable limit of safe exposure to dioxins, as to developmental effects and cancer. The exceptionally wide inter- and intraspecies differences in sensitivity to dioxins will be scrutinised to diminish this major uncertainty factor in risk assessment. To achieve this general objective, a number of specific objectives are set:

  1. To study the molecular mechanisms of dioxin toxicity in a multidisciplinary manner, utilising the mutated receptor causing a remarkable resistance towards dioxin toxicity
  2. To resolve in population studies the sensitivity of human being to developmental effects (tooth defect and cleft palate) cancer, and compare these outcomes to results in experimental animals.
  3. To perform an up-to-date dioxin risk assessment.

    4. Fragrance chemical allergy: a major environmental and consumer health problem in europe

    Contract no : QKL4-1999-01558
    Co-ordinator: Prof. Jean-Pierre Lepoittevin

    The main objective of the project is the prevention of fragrance chemical allergy in non sensitised (primary prevention) and in already sensitised (secondary prevention) individuals. The aim of the primary prevention part of the study is to create initiatives that regulate the exposure to fragrance chemicals so that the induction of allergic contact sensitisation does not take place. This includes identification and validation of fragrance sensitisers including new emerging ones (SAR methods) and insight to their sensitising potential through predictive studies and QSAR analysis. The secondary prevention part of the study will establish measures aiming to avoid the elicitation of the skin disease in already fragrance sensitised individuals. It will include standardisation of diagnostic methods to identify the individuals at risk, epidemiological clinical studies combined with exposure assessment, and cross- reactivity studies aiming at allergenic fragrance chemical substitution.

    The results of the different studies will be compiled in a risk assessment model providing the basis for preventive measures.

    Developmental neurotoxicity of polybrominated diphenylether: mechanisms and effects

    Contract no: QLK4-1999-01562
    Co-ordinator: Prof. Dr Herbert Wiegand

    The goal of the proposal is to elucidate the effects of developmental exposure of animals to flame retardants Polybrominated Diphenyl Ethers (PBDE) on CNS.

    Epidemiological studies indicate a marked increase of PBDE levels in breast milk. In contrast, effects of PBDEs on the developing CNS are largely unknown. Therefore, the aims of the proposal are:

    1. to assess several neurobehavioral endpoints after perinatal treatment of animals for characterisation of possible impairments;
    2. to relate neurobehavioral effects to electrophysiological effects in the different brain areas;
    3. to compare perinatal with adult exposure in order to examine if the developing CNS is particularly susceptible to PBDEs;
    4. to compare different animal species for generalisation of the findings;
    5. to characterise mechanisms of PBDE neural toxicity at cellular and molecular levels including neurotransmitters, receptors and intracellular signal transduction pathways
    6. to examine if exposure alters sexual differentiation of the brain.

    Different dose levels of PBDEs will be studied. PBDE exposure will be compared with PCB-induced effects to relate findings to a better examined substance group.

    New bio-markers of oxidative stress to humans: a role in developing new strategies for human protection against environmental (uva) damage to skin

    Contract no : QLK4-1999-01590
    Co-ordinator: Professor Rex Tyrrell

    The objective of this proposal is to develop new bio-markers based on changes in gene expression and mitochondrial damage which may be used to monitor exposure and susceptibility to oxidative stress from the environment and to validate this methodology using the model of acute and chronic skin exposure to the environmental oxidising carcinogen, ultraviolet A radiation. The major dietary antioxidant phenolic compounds and their metabolites will then be examined for a potential protective role in the skin against environmental stress.