David A Basketter

BASF SE, Ludwigshafen, Rheinland-Pfalz, Germany

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Publications (472)1341.15 Total impact

  • D.A. Basketter · I. R. White · J. P. McFadden · I. Kimber
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    ABSTRACT: Skin sensitization associated with allergic contact dermatitis is a common health problem and is an important consideration for toxicologists in safety assessment. Historically, in vivo predictive tests have been used with good success to identify substances that have the potential to induce skin sensitization, and these tests formed the basis of safety evaluation. These original tests are now being replaced gradually either by in vitro assays or by further refinements of in vivo methods such as the local lymph node assay. Human data have also been available to inform classification decisions for some substances and have been used by risk managers to introduce measures for exposure reduction. However, humans encounter hazards in the context of exposure rather than in the form of intrinsic hazards per se, and so in this article, we have examined critically the extent to which human data have been used to refine classification decisions and safety evaluations. We have also evaluated information on the burden of human allergic skin disease and used this to address the question of whether, and to what extent, the identification and evaluation of skin sensitization hazards has led to an improvement of public and/or occupational health.
    No preview · Article · Dec 2015 · Human & Experimental Toxicology
  • David Basketter · Bob Safford
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    ABSTRACT: Toxicological risk assessment informs exposure limits, so the potential for adverse effects to human health are minimised or avoided. For skin sensitisers, the situation is complicated by asymptomatic induction of contact allergy, a necessary prerequisite for expression of the disease allergic contact dermatitis (ACD). For fragrance skin sensitisers, the development of quantitative risk assessment (QRA) arose from the need to improve the extent to which contact allergy occurred. However, the perceived impact has been less than anticipated. Accordingly, the science and assumptions upon which QRA was founded have been scrutinised and proposals for refinement have been made. In addition, areas of uncertainty have been made explicit, e.g. inter-individual variability and the impact of concomitant disease, clarifying where numerical safety assessment factors are based on expert judgement. Also, the relatively small contribution of factors eg. age, gender, ethnic origin, vehicle matrix and skin permeability are highlighted by reference to the (now controversial) human experiments carried out in the second half of the last century. Adoption and widespread implementation of the current recommendations for QRA, taken in concert with improved assessment of aggregate exposure from multiple sources, should ensure that the frequency of contact allergy will decrease over the coming years.
    No preview · Article · Nov 2015 · Regulatory Toxicology and Pharmacology
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    ABSTRACT: In the two years since the last workshop report, the environment surrounding the prediction of skin sensitisation hazards has experienced major change. Validated non-animal tests are now OECD Test Guidelines. Accordingly, the recent cross sector workshop focused on how to use in vitro data for regulatory decision-making. After a review of general approaches and six case studies, there was broad consensus that a simple, transparent stepwise process involving non-animal methods was an opportunity waiting to be seized. There was also strong feeling the approach should not be so rigidly defined that assay variations/additional tests are locked out. Neither should it preclude more complex integrated approaches being used for other purposes, e.g. potency estimation. All agreed the ultimate goal is a high level of protection of human health. Thus, experience in the population will be the final arbiter of whether toxicological predictions are fit for purpose. Central to this is the reflection that none of the existing animal assays is perfect; the non-animal methods should not be expected to be so either, but by integrated use of methods and all other relevant information, including clinical feedback, we have the opportunity to continue to improve toxicology whilst avoiding animal use.
    Full-text · Article · Oct 2015 · Regulatory Toxicology and Pharmacology
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    Full-text · Dataset · Sep 2015
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    ABSTRACT: Enzyme proteins have potential to cause occupational allergy/asthma. Consequently, as users of enzymes in formulated products, the detergents manufacturers have implemented a number of control measures to ensure that the hazard does not translate into health effects in the workforce. To that end, trade associations have developed best practice guidelines which emphasize occupational hygiene and medical monitoring as part of an effective risk management strategy. The need for businesses to recognize the utility of this guidance is reinforced by reports where factories which have failed to follow good industrial hygiene practices have given rise to incidences of occupational allergy. In this paper, an overview is provided of how the industry guidelines are actually implemented in practice and what experience is to be derived therefrom. Both medical surveillance and air monitoring practices associated with the implementation of industry guidelines at approximately 100 manufacturing facilities are examined. The data show that by using the approaches described for the limitation of exposure, for the provision of good occupational hygiene and for the active monitoring of health, the respiratory allergenic risk associated with enzyme proteins can been successfully managed. This therefore represents an approach that could be recommended to other industries contemplating working with enzymes.
    Preview · Article · Feb 2015 · Journal of Occupational and Environmental Hygiene
  • David A Basketter · Sylvie Lemoine · John P McFadden
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    ABSTRACT: The induction of contact allergy to fragrance ingredients and the consequent risk of allergic contact dermatitis (ACD) present a human health concern that cannot be ignored. The problem arises when exposure exceeds safe levels, but the source(s) of exposure which lead to induction often remain unclear. This contrasts with the elicitation of ACD, where the eczema frequently can be traced to specific source(s) of skin exposure. Cosmetic products are often implicated, both for induction and elicitation. However, other products contain fragrance ingredients, including household cleaning products. In this paper, the risk assessment concerning the ability of these products to induce fragrance contact allergy is considered and the clinical evidence for the induction and/or elicitation of ACD is reviewed. It can be concluded that the risk of the induction of fragrance contact allergy from household cleaning products is low. Especially where more potent fragrance allergens are used in higher exposure products, the aggregated exposure from such products can augment the risk for the elicitation of ACD. This supports the need to manage this risk via the provision of information to consumers.
    No preview · Article · Dec 2014 · European journal of dermatology: EJD
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    Anne Marie Api · David Basketter · Jon Lalko
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    ABSTRACT: Abstract Quantitative risk assessment for skin sensitization is directed towards the determination of levels of exposure to known sensitizing substances that will avoid the induction of contact allergy in humans. A key component of this work is the predictive identification of relative skin sensitizing potency, achieved normally by the measurement of the threshold (the "EC3" value) in the local lymph node assay (LLNA). In an extended series of studies, the accuracy of this murine induction threshold as the predictor of the absence of a sensitizing effect has been verified by conduct of a human repeated insult patch test (HRIPT). Murine and human thresholds for a diverse set of 57 fragrance chemicals spanning approximately four orders of magnitude variation in potency have been compared. The results confirm that there is a useful correlation, with the LLNA EC3 value helping particularly to identify stronger sensitizers. Good correlation (with half an order of magnitude) was seen with three-quarters of the dataset. The analysis also helps to identify potential outlier types of (fragrance) chemistry, exemplified by hexyl and benzyl salicylates (an over-prediction) and trans-2-hexenal (an under-prediction).
    Full-text · Article · Nov 2014 · Cutaneous and Ocular Toxicology
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    ABSTRACT: Integrated testing strategies (ITS), as opposed to single definitive tests or fixed batteries of tests, are expected to efficiently combine different information sources in a quantifiable fashion to satisfy an information need, in this case for regulatory safety assessments. With increasing awareness of the limitations of each individual tool and the development of highly targeted tests and predictions, the need for combining pieces of evidence increases. The discussions that took place during this workshop, which brought together a group of experts coming from different related areas, illustrate the current state of the art of ITS, as well as promising developments and identifiable challenges. The case of skin sensitization was taken as an example to understand how possible ITS can be constructed, optimized and validated. This will require embracing and developing new concepts such as adverse outcome pathways (AOP), advanced statistical learning algorithms and machine learning, mechanistic validation and "Good ITS Practices".
    Full-text · Article · Nov 2014
  • J. P. McFadden · J. P. Thyssen · D.A. Basketter · P. Puangpet · I. Kimber
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    ABSTRACT: During the last 50 years there has been a significant increase in Western societies of atopic disease and associated allergy. The balance between functional subpopulations of Th cells determines the quality of immune response provoked by antigen. One such subpopulation – Th2 cells – is associated with the production of IgE antibody and atopic allergy, whereas, Th1 cells antagonise IgE responses and the development of allergic disease. In seeking to provide a mechanistic basis for this increased prevalence of allergic disease one proposal has been the ‘hygiene hypothesis’ which argues that in westernised societies reduced exposure during early childhood to pathogenic microorganisms favours the development of atopic allergy.Pregnancy is normally associated with Th2 skewing, that persists for some months in the neonate before Th1/Th2 realignment occurs. In this review we consider the immunophysiology of Th2 immune skewing during pregnancy. In particular, we explore the possibility that altered and increased patterns of exposure to certain chemicals have served to accentuate this normal Th2 skewing and therefore promote further the persistence of a Th2 bias in neonates. Furthermore we propose that the more marked Th2 skewing observed in first pregnancy may, at least in part, explain he higher prevalence of atopic disease and allergy in the first born.This article is protected by copyright. All rights reserved.
    No preview · Article · Oct 2014 · British Journal of Dermatology
  • Ian Kimber · Rebecca J Dearman · David A Basketter
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    ABSTRACT: Sensitization of the respiratory tract by chemicals resulting in rhinitis and asthma is an important occupational health issue. Occupational asthma is associated with significant morbidity and can be fatal. Tests for the identification and characterization of chemicals with the potential to cause sensitization of the respiratory tract are lacking. In spite of sustained interest there are no validated or widely accepted methods available, and this presents toxicologists with a considerable challenge. One important constraint on the development of appropriate testing strategies has been uncertainty and controversy about the immunological mechanisms through which chemicals may induce sensitization of the respiratory tract. By analogy with protein respiratory allergy it is legitimate to consider that IgE antibody-dependent mechanisms may play a pivotal role. However, although many aspects of chemical respiratory allergy are consistent with reactions caused by IgE antibody, uncertainty remains because among patients with occupational asthma caused by chemical respiratory allergens there are commonly a proportion, and sometimes a significant proportion, of subjects that lack detectable IgE antibody. Here we consider the relevance of IgE antibody responses for the development of a chemical respiratory allergy to diisocyanates. A case is made that IgE antibody responses are, either directly or indirectly, closely associated with occupational asthma to the diisocyanates (and to other chemical respiratory allergens). As such the argument is advanced here that IgE antibody represents an appropriate readout for the characterization of chemical respiratory allergens, and that uncertainty about mode of action should no longer represent a hurdle in the development of suitable test methods. Copyright © 2014 John Wiley & Sons, Ltd.
    No preview · Article · Oct 2014 · Journal of Applied Toxicology
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    ABSTRACT: Since March 2013, animal use for cosmetics testing for the European market has been banned. This requires a renewed view on risk assessment in this field. However, in other fields as well, traditional animal experimentation does not always satisfy requirements in safety testing, as the need for human-relevant information is ever increasing. A general strategy for animal-free test approaches was outlined by the US National Research Council's vision document for Toxicity Testing in the 21st Century in 2007. It is now possible to provide a more defined roadmap on how to implement this vision for the four principal areas of systemic toxicity evaluation: repeat dose organ toxicity, carcinogenicity, reproductive toxicity and allergy induction (skin sensitization), as well as for the evaluation of toxicant metabolism (toxicokinetics) (Fig. 1). CAAT-Europe assembled experts from Europe, America and Asia to design a scientific roadmap for future risk assessment approaches and the outcome was then further discussed and refined in two consensus meetings with over 200 stakeholders. The key recommendations include: focusing on improving existing methods rather than favoring de novo design; combining hazard testing with toxicokinetics predictions; developing integrated test strategies; incorporating new high content endpoints to classical assays; evolving test validation procedures; promoting collaboration and data-sharing of different industrial sectors; integrating new disciplines, such as systems biology and high throughput screening; and involving regulators early on in the test development process. A focus on data quality, combined with increased attention to the scientific background of a test method, will be important drivers. Information from each test system should be mapped along adverse outcome pathways. Finally, quantitative information on all factors and key events will be fed into systems biology models that allow a probabilistic risk assessment with flexible adaptation to exposure scenarios and individual risk factors.
    Full-text · Article · Jul 2014
  • David Basketter · Ian R White · John P McFadden · Ian Kimber
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    ABSTRACT: Abstract Background: Hexyl cinnamal (HCA) is a widely used fragrance chemical, the low skin-sensitizing potency of which has made it a common choice for the use as a positive control for predictive toxicology assays. However, HCA is commonly negative in current candidate in vitro alternatives test methods. Objective: To review the evidence that HCA is a classifiable skin sensitizer against the standards set by the Globally Harmonized Scheme (GHS), and determine whether it represents an appropriate choice for a positive control substance for predictive testing. Methods: Using the GHS criteria, mechanistic data, and in vitro, in vivo and human evidence relating to HCA and skin sensitization have been reviewed. Results: The chemistry of HCA is consistent with potential for skin sensitization and predictive in vivo test data support this conclusion. However, the human data are relatively sparse, consistent with HCA possessing a low capacity to induce skin sensitization under conditions of consumer exposures. Conclusions: Using GHS criteria (and applying a precautionary approach) HCA would classify as a weaker skin sensitizer than predicted by the local lymph node assay (LLNA). However, given the human experience, it is necessary to consider whether HCA is the most appropriate choice for use as a positive regulatory control.
    No preview · Article · Jul 2014 · Cutaneous and Ocular Toxicology
  • David Basketter · Ian Kimber
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    ABSTRACT: The identification, characterisation, risk assessment and risk management of materials that cause allergic sensitisation is an important requirement for human health protection. It has been proposed that for some chemical and protein allergens, and in particular for those that cause sensitisation of the respiratory tract (associated with occupational asthma), it may be appropriate to regard them as Substances of Very High Concern (SVHC) under the provisions of REACH (Registration, Evaluation, Authorisation and restriction of CHemicals). We have argued previously that categorisation of sensitising agents as SVHC should be used only in exceptional circumstances. In the present article, the subject of SVHC is addressed from another perspective. Here the information that would be required to provide a compelling case for categorisation of a skin sensitising substance as a SVHC is considered. Three skin sensitising chemicals have been identified to serve as working examples. These are chromate, a potent contact allergen, and the skin sensitisers formaldehyde and isoeugenol. The key criterion influencing the decision regarding a skin sensitiser being categorized as SVHC is the extent to which impacts on the quality of life are reversible. Consequently, SVHC categorisation for skin sensitising chemicals should be used only in exceptional circumstances.
    No preview · Article · May 2014 · Regulatory Toxicology and Pharmacology
  • Ian Kimber · David A Basketter
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    ABSTRACT: Characterisation of the relative sensitizing potency of protein and chemical allergens remains challenging, particularly for materials causing allergic sensitization of the respiratory tract. There nevertheless remains an appetite, for priority setting and risk management, to develop paradigms that distinguish between individual respiratory allergens according to perceptions of the hazards and risks posed to human health. One manifestation thereof is recent listing of certain respiratory allergens as Substances of Very High Concern (SVHC) under the provisions of REACH (Registration, Evaluation, Authorisation and restriction of CHemicals). Although priority setting is a laudable ambition, it is important the process is predicated on evidence-based criteria that are transparent, understood and owned. The danger is that in the absence of rigorous criteria unwanted precedents can be created, and confidence in the process is compromised. A default categorisation of sensitisers as SVHC requiring assessment under the authorisation process is not desirable. We therefore consider here the value and limitations of selective assignment of certain respiratory allergens as being SVHC. The difficulties of sustaining such designations in a sound and equitable way is discussed in the context of the challenges that exist with respect to assessment of potency, and information available regarding the effectiveness of exposure-based risk management.
    No preview · Article · Apr 2014 · Regulatory Toxicology and Pharmacology
  • Ian Kimber · Rebecca J. Dearman · David A. Basketter · Darrell R. Boverhof
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    ABSTRACT: Allergic sensitisation of the respiratory tract by chemicals is associated with rhinitis and asthma and remains an important occupational health issue. Although less than 80 chemicals have been confirmed as respiratory allergens the adverse health effects can be serious, and in rare instances can be fatal, and there are, in addition, related socioeconomic issues. The challenges that chemical respiratory allergy pose for toxicologists are substantial. No validated methods are available for hazard identification and characterisation, and this is due in large part to the fact that there remains considerable uncertainty and debate about the mechanisms through which sensitization of the respiratory tract is acquired. Despite that uncertainty, there is a need to establish some common understanding of the key events and processes that are involved in respiratory sensitisation to chemicals and that might in turn provide the foundations for novel approaches to safety assessment. In recent years the concept of Adverse Outcome Pathways (AOP) has gained some considerable interest among the toxicology community as a basis for outlining the key steps leading to an adverse health outcome, while also providing a framework for focusing future research, and for developing alternative paradigms for hazard characterisation. Here we explore application of the same general principles to an examination of the induction by chemicals of respiratory sensitization. In this instance, however, we have chosen to adopt a reverse engineering approach and to model a possible AOP for chemical respiratory allergy working backwards from the elicitation of adverse health effects to the cellular and molecular mechanisms that are implicated in the acquisition of sensitisation.
    No preview · Article · Apr 2014 · Toxicology
  • David A Basketter · G Frank Gerberick · Ian Kimber
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    ABSTRACT: Toxicology endeavors to predict the potential of materials to cause adverse health (and environmental) effects and to assess the risk(s) associated with exposure. For skin sensitizers, the local lymph node assay was the first method to be fully and independently validated, as well as the first to offer an objective end point with a quantitative measure of sensitizing potency (in addition to hazard identification). Fifteen years later, it serves as the primary standard for the development of in vitro/in chemico/in silico alternatives.
    No preview · Article · Mar 2014 · Dermatitis
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    ABSTRACT: The skin has a sophisticated and highly orchestrated immune system. The ability of proteins encountered at skin surfaces to access that immune system remains controversial, however. In this article the question considered is whether proteins encountered epicutaneously (on the skin) at abraded or tape-stripped skin surfaces, but also at sites where the skin is intact, can engage with the cutaneous immune system to provoke and regulate responses. The available evidence suggests that epicutaneous exposure to foreign proteins is able to elicit immune and allergic responses, and that encounter with protein via this route may favour the development of selective Th2 responses and allergic sensitisation. It is also clear that proteins can modify immunological function when delivered topically and that intact skin may provide an effective route of exposure for active immunotherapy of allergic disease. An appreciation that epicutaneously applied proteins can interact with the skin immune system, even when delivered at intact skin sites, opens up important opportunities for immunotherapy, local immune modulation and the treatment of inflammatory skin diseases. It also indicates that this route of exposure must be considered as part of the safety assessment and risk management of protein-induced allergic sensitisation.
    No preview · Article · Feb 2014
  • Marc Vocanson · Jean-Francois Nicolas · David Basketter
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    ABSTRACT: Allergic contact dermatitis is a disease that to a great extent can be limited or even avoided. Limitation of allergic contact dermatitis can be realized by the predictive identification of sensitizing chemicals (hazard identification), measurement of their relative sensitizing potency (hazard characterization) and subsequent use of proper risk assessment/management strategies in relation to the anticipated skin exposure. Several in vivo methods exist that are known to be reliable predictors of chemicals that can behave as skin sensitizers. One particular method, the local lymph node assay, also produces vital information on the relative potency of identified sensitizers. This potency information can be applied to quantitative risk assessment for skin sensitization, although the completion of quantitative risk assessment is dependent also on access to information on human skin exposure. However, the challenge in 2013 is how to obtain the same type of information on the potency of skin sensitising chemicals using only in vitro and in silico methods. With the impending elimination of in vivo tests, the in vitro test development focus has been on the essential mechanistic steps of sensitization induction, including hapten–peptide binding, dendritic cell migration/maturation and T-lymphocyte priming. Several in vitro methods appear close to successful validation for hazard identification. What has to be addressed is how information from such in vitro assays is integrated, together with data on epidermal bioavailability, to deliver hazard characterization in the form of assessment of sensitizer potency. More than a single protocol, a battery of different in vitro tests will be probably necessary to optimize the detection of skin sensitizers.
    No preview · Article · Jan 2014 · Expert Review of Dermatology
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    ABSTRACT: Although adoption of skin sensitization in vivo assays for hazard identification is likely to be successful in the next few years, this does not replace their use in potency prediction. Notably, measurement of potency of skin sensitizers in the local lymph node assay has been important. However, this local lymph node assay potency measure has not been formally assessed against a range of substances of known human sensitizing potential, because the latter is lacking. Accordingly, criteria for human data have been established that characterize 6 categories of human sensitizing potency, with 1 the most potent and 5 the least potent; category 6 represents true nonsensitizers. The literature has been searched, and 131 chemicals assigned into these categories according to their intrinsic potency judged only by the available human information. The criteria and data set generated provide a basis for examination of the capacity of nonanimal approaches for the determination of human sensitization potency.
    Full-text · Article · Jan 2014 · Dermatitis
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    David Basketter · Ian Kimber
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    ABSTRACT: The identification, characterisation, risk assessment and risk management of materials that cause allergic sensitisation is an important requirement for human health protection. It has been proposed that for some chemical and protein allergens, and in particular for those that cause sensitisation of the respiratory tract (associated with occupational asthma), it may be appropriate to regard them as Substances of Very High Concern (SVHC) under the provisions of REACH (Registration, Evaluation, Authorisation and restriction of CHemicals). We have argued previously that categorisation of sensitising agents as SVHC should be used only in exceptional circumstances. In the present article, the subject of SVHC is addressed from another perspective. Here the information that would be required to provide a compelling case for categorisation of a skin sensitising substance as a SVHC is considered. Three skin sensitising chemicals have been identified to serve as working examples. These are chromate, a potent contact allergen, and the skin sensitisers formaldehyde and isoeugenol. The key criterion influencing the decision regarding a skin sensitiser being categorized as SVHC is the extent to which impacts on the quality of life are reversible. Consequently, SVHC categorisation for skin sensitising chemicals should be used only in exceptional circumstances.
    Preview · Article · Jan 2014 · Regulatory Toxicology and Pharmacology

Publication Stats

15k Citations
1,341.15 Total Impact Points


  • 2011
    • BASF SE
      Ludwigshafen, Rheinland-Pfalz, Germany
  • 2010-2011
    • The University of Manchester
      • Faculty of Life Sciences
      Manchester, England, United Kingdom
  • 1988-2009
    • Unilever
      Londinium, England, United Kingdom
  • 2008
    • Technical University of Denmark
      • Division of Toxicology and Risk Assessment
      Lyngby, Capital Region, Denmark
  • 1999-2008
    • Procter & Gamble
      Cincinnati, Ohio, United States
  • 2007
    • Státní Zdravotní Ústav
      Praha, Praha, Czech Republic
  • 2005
    • St. Thomas University
      Fredericton, New Brunswick, Canada
  • 2003
    • Imperial College London
      • Division of Molecular Biosciences
      Londinium, England, United Kingdom
  • 2001
    • Pennsylvania State University
      University Park, Maryland, United States
  • 1997
    • Helsinki University Central Hospital
      Helsinki, Uusimaa, Finland
  • 1991-1995
    • European Centre for Ecotoxicology and Toxicology of Chemicals
      Bruxelles, Brussels Capital, Belgium
  • 1994
    • Liverpool John Moores University
      • School of Pharmacy and Biomolecular Sciences
      Liverpool, England, United Kingdom