Proposal for a Brazilian Centre on Alternative Test Methods

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Proposal for a Brazilian Centre on Alternative Test Methods

Chantra Eskes1*, Jadir Nunes2, Octavio Presgrave3, Dermeval de Carvalho4, Ekaterina Rivera5, Thomas Hartung6, Sandra Coecke7, Philippe Masson8, Joachim Kreysa7 and Vanessa de Moura Sá-Rocha9

1 Independent Consultant, Ispra, Italy; 2 Brazilian Association of Cosmetology, São Paulo (SP), Brazil; 3 National Institute of Quality Control in Health (INCQS), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro (RJ), Brazil; 4 Biotox, Ribeirão Preto, SP, Brazil; 5 Biological Science Institute, Federal University of Goiás, Brazil; 6 Johns Hopkins University, Baltimore, USA and University of Konstanz, Germany; 7 ECVAM, In Vitro Methods Unit, Institute for Health and Consumers Protection, European Commission Joint Research Centre, Ispra, Italy; 8 EVIC International, Paris, France; 9 Natura, Cajamar, SP, Brazil

Published: March 4, 2010
The following article is a condensed version of an article published in ALTEX: Eskes, C., Sá-Rocha, V., Nunes, J., Presgrave, O., de Carvalho, D., Masson, P., et al. (2009). Draft Proposal for a Brazilian Centre on Alternative Test Methods. ALTEX. 26, 295-298. Available here

About the Author(s)
Chantra Eskes, Ph.D. worked for many years at the European Center for the Validation of Alternative Methods (ECVAM) where she was responsible for the area of eye irritation, and served as scientific officer for the cosmetics and topical toxicity areas. She comes from a Dutch and Brazilian background, and obtained an Engineer and Master Degrees in Food Sciences and Technology in France, followed by a Ph.D. on in vitro neurotoxicology obtained at the faculty of medicine of Lausanne in Switzerland.

At ECVAM, her work consisted in the coordination and management of validation studies on alternative methods for eye and skin irritation, and on the regulatory issues related to the EU Cosmetics Directive. Her activities contributed to the evaluation of 15 alternatives to animal testing, the participation in four international validation studies, six alternative test methods being validated, one EU test guideline adopted on a replacement alternative test method to skin irritation testing, and two OECD test guidelines accepted as partial replacement alternatives for eye irritation testing. For her contributions, she has been awarded the European Commission Joint Research Center Excellence Award for the Support to EU Policy in 2009.

Currently Chantra acts as an independent consultant on in vitro toxicology for regulatory and industrial purposes. She’s editor, author, and co-author of a number of scientific monographs. She’s also on the Executive Board from the European Society of In Vitro Toxicology (ESTIV), and acts as reviewer for several scientific journals in the field of in vitro toxicology.

Dr. Chantra Eskes
Email: eskesch@yahoo.com
Jadir Nunes received a Bachelors degree in Pharmacy and Biochemistry and a Masters and Ph.D. in Pharmacotechnics / Cosmetic Sciences (USP), all from the University of São Paulo (USP). Post graduation Dr. Nunes studied Marketing – Latu Sensu (ESPM), as well as several short courses/seminars and training programs attended in Oxford (England), Dusseldorf (Germany), Cannes, Bordeaux (France), Brussels (Belgium) and North Carolina, New Jersey (USA). Dr. Nunes’ professional career developed in the areas of research, development, quality control and clinical evaluations of cosmetic, pharmaceutical products and ingredients, for national and multinational companies, such as Johnson & Johnson, Schering-Plough, Natura, Chemyunion, Evic Brasil and Arch Chemicals. Currently Dr. Nunes is Director of R&D Latin America of Stiefel/GSK Company, ABC Vice President – Brazilian Society of Cosmetic Sciences, and Presidium Member of the International Federation Societies of Cosmetic Chemists.

Dr. Jadir Nunes
Email: jnunes@stiefel.com

 

Dermeval de Carvalho is a pharmacist, retired Professor of Toxicology at the College of Pharmacy, Ribeirao Preto Campus, University of Sao Paulo, Brasil, and Scientific Director of Biotox Consultant (Brasil).

Dr. Dermaval de Carvalho
Email: biotox@biotox.com.br

 

Ekaterina Akimovna Botovchenco Rivera is a veterinarian, member of the ad hoc group on laboratory animal welfare OIE/OMSA(Organization Mondiale de la Santé Animale) in Paris, Director of Laboratory Animal House/University of Goiás-UFG (Brasil), and the Brazil representative to the International Council on Laboratory Animal Science. Dr. Rivera was a consultant for the Brazilian Environmental Agency (IBAMA) on laboratory animal tests (1997-2005).

Dr. Ekaterina Rivera
Email: e.rivera@uol.com.br

 

Thomas Hartung, M.D., Ph.D. is the new Director of the Center for Alternatives to Animal Testing (CAAT) and the inaugural Doerenkamp-Zbinden Chair for Evidence-based Toxicology in the Department of Environmental Health Sciences at the Johns Hopkins University Bloomberg School of Public Health.

In 1991, Dr. Hartung received a Ph.D. in Biochemical Pharmacology from the University of Konstanz, Germany, and an M.D. in Toxicology in 1992 from the University of Tubingen. He completed his medical internship at the University of Freiburg in surgery at the hospital of Singen, Germany.

Dr. Hartung joined the faculty at University of Konstanz in 1994, where he served as an Assistant Professor of Biochemical Pharmacology until 1999, and then as an Associate Professor until 2002. He has been an honorary full professor of Pharmacology at Konstanz since 2003. From 1996 to 2002, Dr. Hartung also served as the CEO of the Steinbeis Technology Transfer Center for In Vitro Pharmacology and Toxicology (InPuT).

In 2002, Dr. Hartung became the Head of the European Centre for Alternative Methods (ECVAM) at the European Commission Joint Research Centre in Italy. As Head of ECVAM, he was integral in accelerating the alternative methods validation process, and in establishing a network of more than 400 experts from all stakeholder groups to facilitate global regulatory harmonization in toxicity testing.

Dr. Thomas Hartung
Johns Hopkins Center for Alternatives to Animal Testing
615 N Wolfe Street, W7032
Baltimore, MD 21205
Email: thartung@jhsph.edu
Sandra Coecke (F) is by training a University Engineer with specialisation in Biotechnology. She has a Ph.D. in Medicine and Pharmaceutical Sciences (Vrije Universiteit Brussels) exploring an in vitro approach to study hormonal regulation of the biotransformation enzymes flavin-containing monooxygenase and glutathione S-transferases in rat liver. She was responsible for the setting up of the In Vitro Toxicology Laboratory at Janssen Pharmaceutica, Belgium, in 1993. In 1994 she was awarded the International Prize from the Foundation for the Substitution of Animal Experimentation, in Luxembourg, based on her work in the field of metabolism and novel in vitro cell culture systems in general. In 1996 she joined the European Centre for the Validation of Alternative Methods, European Commission (EC), Joint Research Centre (JRC), Ispra, Italy. Currently, she is heading the JRC competence group on In-house Validation and Training at the EC JRC Institute for Health and Consumer Protection and is responsible for all validation studies carried out in-house. A Chemical Repository is hosted in her group. With over 20 years experience in in vitro toxicology and over 80 papers on in vitro toxicology, she acquired a strong research background in the fields of in vitro metabolism/xenobiotic biotransformation in hepatocyte cultures, in vitro neurotoxicity/developmental neurotoxicity and in vitro topical toxicity (eye and skin irritation) test models, new advanced technologies in in vitro toxicology testing systems, quality control and the management of ongoing large international collaborative European research projects (Acutetox-in vitro acute toxicity integrated testing strategy, Vitrocellomics-omics and stem cell-based technologies, and Artemis- in vitro neutral tissue system for replacement of transgenic animals with memory/learning deficiencies). She also has run several pre-validation and formal validation studies.

Dr. Sandra Coecke
EC-Joint Research Centre, Ispra site
Via Enrico Fermi 2749
I-21027 Ispra (VA), Italy
Email: sandra.coecke@jrc.ec.europa.eu
Joachim Kreysa, Ph.D., joined the European Commission in 1985, working for 10 years in research management. This was followed by 5 years as scientific secretary of the Scientific Steering Committee that advised the Commission on BSE and similar highly sensitive matters, including overseeing the validation of BSE tests. Thereafter he managed development projects, ran a competition task force, and helped set-up the European Chemicals Agency in Helsinki, the centre-piece of REACH, later joining the founding team as Director for Cooperation of ECHA, being responsible for setting up and running the REACH-Helpdesks and preparing guidance for industry, setting-up the Agency’s scientific committees, and creating the communication unit of ECHA. Since November, 2008 he heads the In Vitro Methods Unit of the Institute for Health and Consumer Protection IHCP of the Joint Research Center and is also responsible for ECVAM, which is now a Policy Support Action of the IHCP.

Dr. Joachim Kreysa
Directorate General JRC
B-1049 Brussels BELGIUM
Email: joachim.kreysa@ec.europa.eu
Vanessa de Moura Sá Rocha received a Bachelors degree in Veterinarian, a Masters in Pathology, and a Ph.D. in Sciences from the University of São Paulo, Brazil. She is responsible for coordination and implementation of studies on alternative methods at Natura, a cosmetic Brazilian Company.

Dr. Vanessa de Moura Sá Rocha
Email: vanessarocha@natura.net

Background

Several initiatives have taken place in Brazil to foster the creation of a center dedicated to alternatives to animal testing.

These initiatives include the following:

  • In 2005, a meeting on alternative test methods for regulatory use named EMALT (Encontro sobre Métodos Alternativos ao Uso de Animais para Fins Regulatórios) was organized by the Brazilian National Institute of Quality Control in Health (Instituto Nacional de Controle e Qualidade Sanitária or INCQS). It comprised around a hundred participants from the Brazilian authorities and major stakeholders in the field of toxicological testing including representatives from the European Centre for the Validation of Alternative Methods (ECVAM). The aim of this meeting was to initiate discussions on the processes of funding, developing, and validating alternative methods in Brazil (Presgrave and Bhogal, 2005).
  • In 2008, a new law was adopted in Brazil regarding the use of animals for scientific purposes (law n.º 11.794). It establishes amongst other provisions the task to monitor and evaluate the introduction of alternative methods. However, the promotion and dissemination of information on existing alternative methods to the large Brazilian scientific community are not foreseen within such legislation.
  • In August 2008, Dr. Vanessa Sá-Rocha from Natura, an important Brazilian cosmetics company, organized a meeting among Brazilian regulatory authorities and major stakeholders including ECVAM, to foster discussions again on funding, developing, and validating alternative methods for toxicity testing in Brazil.
  • In November-December 2008, Dr. Jadir Nunes from the Brazilian Association of Cosmetology, together with Prof. Dermeval de Carvalho, presented a proposal to the Brazilian National Agency of Health Surveillance (Agência Nacional de Vigilância Sanitária or ANVISA) for the creation of a Centre for the Validation of Alternative Methods.
  • In December 2008, Dr. Octavio Presgrave from the INCQS published a scientific article on “The need for the Establishment of a Brazilian Centre for the Validation of Alternative Methods” (Presgrave, 2008).
  • In order to streamline the different activities undertaken, Dr. Chantra Eskes acted as a facilitator by establishing a new joint proposal, together with the Brazilian stakeholders currently involved, with the view of setting up a Brazilian Centre on Alternative Test Methods (BCATM; Eskes, et al., 2009). The proposal aims at favoring the development, validating and defining the criteria of acceptance of alternative test methods to be used and/or adapted to the Brazilian regulatory framework. It was proposed as a basis for finding consensus and progressing the initiatives in Brazil.
  • In May 2009, the BCATM joint proposal was submitted together with the previous initiatives to the ANVISA Brazilian Authority, requesting BCATM’s creation. Additional support is also further being sought.
Need for a Brazilian Centre

Regulatory, commercial/industrial, scientific, ethical, national, and international needs would benefit from the creation in Brazil of a centre for the promotion of the 3Rs principles (replacement, reduction, and refinement), and for the validation of alternative test methods.

In the field of regulatory toxicological testing and hazard assessment, several alternatives to animal testing have already been adopted internationally within the Organisation for Economic Cooperation and Development (OECD) Test Guidelines program (e.g., OECD TG 430 to 432, 437, and 438). Several countries/regions have established bodies that focus on the promotion and validation of alternative methods to animal testing, such as ECVAM (Europe/EU), the Interagency Coordinating Committee on the Validation of Alternative Methods or ICCVAM (United States), and the Japanese Center for the Validation of Alternative Methods or JaCVAM (Japan). Other countries, including China, Korea, and India, are establishing similar bodies. The creation of a Brazilian Centre on Alternative Test Methods, and its presence in the national and international arena, represents a requisite to: 1) harmonizing Brazilian standards in the field of alternative methods to animal testing, and whenever applicable its accordance to the internationally agreed guidelines and principles; 2) promoting Brazilian regulatory and commercial requirements in the field of scientific and toxicological testing; and 3) fostering Brazilian communication with international bodies.

Alternative test methods are generally used within industry for screening, efficacy testing, and/or preclinical testing purposes. Brazil is one of the world’s largest economies, and has vast natural resources for the potential discovery and exploitation of novel natural ingredients. Relevant alternative methods may be used to reduce the time needed for screening of new ingredients, decrease its costs as well as the number of animals required with the traditional tests. Alternative methods are already recognized as having the potential to be mechanistically more relevant for predicting some human health effects than traditional animal tests, given, for example, the species differences related to differences in metabolism or so-called biotransformation (Coecke, et al., 2006).

Furthermore, recent European legislation calls for the use of non-animal testing. The European Cosmetics Directive has established a marketing ban which entered into force in March 2009 on cosmetic products containing ingredients that have been tested on animals, and since 2004 on finished cosmetic products tested on animals. In addition, the European regulation on chemicals (REACH) requires toxicological information on around 30,000 existing chemicals. As a base-testing requirement for raw materials marketed in volumes greater than10 tonnes/year, information coming from non-animal testing is required. In order for Brazilian industries to strengthen their international market position and benefit from about 500 million European consumers, the promotion and validation of alternative methods will be essential.

The participation of Brazilian academic scientists and other researchers could lead to the development and validation of alternative methods to animal testing which are more readily accessible and less costly for Brazilian needs compared to methods coming from foreign countries. It could also lead to the development of a new market based on novel in vitro technologies, similarly to what is currently occurring in Europe and in the USA.
The Brazilian Centre on Alternative Test Methods would serve as a focal point for information, discussions, and training to the Brazilian scientific community coming from academia and industry, as well as to regulators, in order to favor a harmonized and common understanding of the principles of the 3Rs, of the validation of alternative test methods, and of the various applications alternative methods can have for basic research, industrial testing, and regulatory testing requirements. In addition, a Brazilian Centre would favor the development and validation of alternative test methods to be used and/or adapted to the Brazilian regulatory framework, as well as defining the criteria for their acceptance.

Proposed Activities of a Brazilian Centre

The role of the Brazilian Centre on Alternative Test Methods (BCATM) is to bridge the needs of different stakeholders in Brazil for alternative test methods by offering the following services:

  • Providing up-to-date information on alternatives to animal testing (the 3Rs principles, standards of internationally agreed requirements, and validated and available alternatives to animal testing) to Brazilian scientists and regulators through a centralized website, database, and publications;
  • Communicating and networking of interested parties through seminars and workshops;
  • Identifying current regulatory and non-regulatory needs of available alternatives;
  • Training and educating on the 3Rs principles, on the principles of validation, and on validated alternative methods;
  • Participating in and coordinating Brazilian and international validation of alternative methods.

The above proposed activities and a structure for the BCATM have been described in greater detail in the full ALTEX article (Eskes et al., 2009).

The Way Forward for Alternative Methods in Brazil

The creation of a Brazilian Centre on Alternative Test Methods as proposed here could widely benefit the scientific and regulatory applications of alternative methods in Brazil. The development of new industries around the cutting edge biotechnologies could enhance economic development. Having “local” alternative methods available could reduce the time and costs of required testing for new ingredients. Addressing international testing requirements such as recent EU legislation would promote Brazil’s participation in international commerce.

The BCATM would be a resource to Brazil scientists and regulators for harmonized education, training, information, consultation, and the coordination of national and international efforts.

Acknowledgement

The authors wish to acknowledge Dr. Sherry Ward for her support and editorial work.
©2010 Chantra Eskes, Jadir Nunes, Octavio Presgrave, Dermeval de Carvalho, Ekaterina Rivera, Thomas Hartung, Sandra Coecke, Philippe Masson, Joachim Kreysa, and Vanessa de Moura Sá-Rocha

References
Brazil. Law n.º 11.794, November 08, 2008.

Coecke, S., Ahr, H., Blaauboer, B.J., Bremer, S., Casati, S., Castell, J., et al. (2006). Metabolism: A Bottleneck in In Vitro Toxicological Test Development. ECVAM Workshop 54. Altern. Lab. Anim. 34, 49-84.

Eskes, C., Sá-Rocha, V., Nunes, J., Presgrave, O., de Carvalho, D., Masson, P., et al. (2009). Draft Proposal for a Brazilian Centre on Alternative Test Methods. ALTEX. 26, 295-298.

Presgrave, O.A. (2008). The Need for the Establishment of a Brazilian Centre for the Validation of Alternative Methods (BraCVAM). Altern. Lab. Anim. 36, 705-708.

Presgrave, O.A. & Bhogal, N. (2005). EMALT: A Brazilian Meeting on Alternative Methods to Animal Use for Regulatory Purposes. Altern. Lab. Anim. 33, 670-672.

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