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Inventory of the Spanish Institutions and Scientists Involved in Alternatives to the use of Laboratory Animals (Refinement, Reduction or Replacement)+

Inventory: 18f. Inventory of Institutions

Type of Institution: Industrial (pharmaceutical Laboratory)

Staff:

Carmen González Martín, Dra Ciencias Biológicas, Jefa de Toxicología, Responsable de Unidad, 50 % time devoted to altern. meth.
Montserrat Gozalo, Lda. Ciencias Biológicas, Técnico Ayudante de Toxicología, 20 % time devoted to altern. meth.
Eva María Archilla, Formación Profesional FP 2, Auxiliar de Toxicología, 100 % time devoted to altern. meth., duties related to altern. meth.: cell culture

Total staff involved in alternative methods is 3 people.

Activities / aims: This industrial (pharmaceutical laboratory) department is mainly involved in basic research, non-regulated applied research, method development and method validation; it performs toxicology testing (mechanisms of toxicity, basal cytotoxicity, acute systemic toxicity, nephrotoxicity, hepatotoxicity, chronic toxicity) on a routine basis. Pharmaceuticals are routinely evaluated; physical agents also being occasionally studied.

The main use of alternative methods is for screening, complementary and replacement tests.

Model systems: The model systems used are conventional animal models and in vitro methods -- cell lines culture (epithelioid (kidney, endothelial)).

The endpoints employed in vitro are morphology (HTD by optical and electronic microscopy), cell viability (neutral red uptake, MTT reduction, LDH), cytoskeleton/membranes/enzyme release (LDH release), cellular proliferation (CFA) and cell signalling (immunofluorescence).

Quality assurance / Validation programmes: A Quality Assurance Unit is operating inside the facility. The institution applies Good Laboratory Practices rules according to OECD

Type of Institution: Private / contract laboratory

Staff:

Elisabeth Carbonell Teruel, Email: elisabet.carbonell@blues.uab.es, Dra. Biología (Genética), Directora Unidad de Genotoxicidad, 100 % time devoted to altern. meth.
Fernando de Cuevillas Matozzi, Email: Fernan_cuevillas@hotmail.com, Dr Químicas, Ldo. Farmacia, Director Unidad Oncología Molecular, 50 % time devoted to altern. meth.
Carmen Montoriol Sabaté, Lda. Farmacia, Respon. Suplente Unidad Oncología Molecular, 50 % time devoted to altern. meth.

Total staff involved in alternative methods is 3 people.

Activities / aims: This private / contract laboratory department is mainly involved in non-regulated applied research, regulatory testing and method development; it performs molecular biology, toxicology testing (genotoxicity / mutagenicity), diagnostics, monitoring --chemical, biological-- and culture methodology studies on a routine basis. Pharmaceuticals, cosmetics, diverse chemical compounds, pesticides, medical devices and biomaterials are routinely evaluated; food additives, colourings and environmental pollutants also being occasionally studied.

The main use of alternative methods is for screening, complementary and replacement studies.

Model systems: The model systems used are in vitro methods - micro-organisms (Salmonella typhimurium, E. coli), primary culture of dispersed cells (human lymphocytes, breast, colon, lung cells, etc) and cell lines culture (solid tumours, L5178).

The endpoints employed are in vitro cell viability (dye uptake), cellular proliferation (flow cytometry), metabolic activity (P450, glutathione S-transferase), nucleic acids (gene mutation (p53), chromosomal breaks, reorganizations (AC, SCE, MN, SCGE)) and defence systems (glycoprotein P).

Experimental systems (examples):

1 Salmonella typhimurium, reversion of mutation, genotoxicity, complementary test
2 human peripheral lymphocytes, chromosomal breaks, genotoxicity, complementary test
3 human peripheral lymphocytes or tissues, BRCA1 gene sequence, diagnostics, screening
4 human peripheral lymphocytes, Philadelphia chromosome, diagnostics, screening

Work lines: Development and implementation of methods of clinical interest on solid and haematological tumours. Genotoxicity evaluation of chemicals. Biomonitoring of workers exposed to pollutants.

Quality assurance / Validation programmes: A Quality Assurance Unit is operating inside the facility. The institution applies Good Laboratory Practices rules according to OECD. The team have previously been involved in the following alternative method validation programmes: Programas Nacionales de Sanidad y de la CEE. They are available to participate in EU validation programmes (all types): in vitro micronuclei assay and comet assay

Sources of financing: "Determinación de la naturaleza del daño genético inducido por distintos agentes genotóxicos utilizando Drossophila y linfocitos humanos como sistema de bioensayo" CICYT, SAF94-0697, 1994-97; genotoxicidad en eucariotas: nuevos estudios sobre sus mecanismos y detección CICyT, SAF95-0813; Colaboración en el "Estudio del diagnóstico de tumores de mama y ovario hereditarios, por secuenciación del gene BRCA1"

Staff:

Lluis Simo I Castells, Ld Ciencias Biológicas, Director Unidad, 20 % time devoted to altern. meth.
Nuria Alvarez Genoher, Ld Ciencias Biológicas, Subdirector Unidad, 30 % time devoted to altern. meth.
Samuel Corcobado Moreno, Téc. Esp. Química, Técnico, 20 % time devoted to altern. meth.
Juan Rodríguez Ruíz, Téc. Esp. de Laboratorio, Técnico, 10 % time devoted to altern. meth.

Total staff involved in alternative methods is 4 people.

Activities / aims: This private / contract laboratory department is mainly involved in regulatory testing; it performs toxicology (acute systemic toxicity, ocular cytotoxicity, dermal irritation and corrosivity, genotoxicity / mutagenicity, ecotoxicity) testing on a routine basis. Pharmaceuticals, cosmetics, medical devices, biomaterials, wastes are routinely evaluated; vaccines, hormones, diverse chemical compounds, pesticides, toxins, food additives, colourings and food also being occasionally studied.

The main use of alternative methods is for screening, complementary and replacement studies.

Model systems: The model systems used are conventional animal models, in vitro methods -- micro-organisms (Photobacterium phosphoreum), culture of explants, reaggregates, reconstituted organs, (skintex, eyetex), primary culture of dispersed cells (rbc)-- and human volunteers (adaptation to the situation).

The endpoints employed are in vivo death, toxicity, irritation, temperature changes, sensibilization / allergy and in vitro morphology, cell viability and metabolic activity enzymes.

Experimental systems (examples):

1 rabbits, temperature, rectal probe, pyrogenicity
2 mice, death, abnormal toxicity (safety)
3 red blood cells, haemolysis, ocular irritation, replacement test
4 micro-organisms, luminescence, wastes, water, replacement test

Work lines: Alternative methods in toxicology

Quality assurance / Validation programmes: A Quality Assurance Unit is operating inside the facility. The institution applies Good Laboratory Practices rules according to OECD. The team are available to participate in EU validation programmes (all types).

Sources of financing: Self financing


Type of Institution: Private / contract laboratory

Staff:

J. Ramón Goya Ramos, Email: rgoya@recol.es, Dr Farmacia, Dr Laboratorio
Paloma Aberturas, Analista Clínico del Laboratorio. Encargada de los tests de esterilidad y pirógenos

Total staff involved in alternative methods is 2 people.

Activities / aims: This private / contract laboratory department is mainly involved in regulatory testing; it performs biochemistry, toxicology (mechanisms of toxicity, acute systemic toxicity, ocular cytotoxicity, dermal irritation, corrosivity, haematoxicity, integrated test strategies) and culture methodology studies on a routine basis. Pharmaceuticals and cosmetics are routinely evaluated, medical devices also being occasionally studied.

The main use of alternative methods is for complementary studies.

Model systems: The model systems used are animal models –conventional.

Work lines: This is a control laboratory authorized by the Ministry of Health for the control of cosmetics, medical equipment, etc. Therefore toxicity, primary irritation, sterility and pyrogens are the main tests carried out at the laboratory.

Quality assurance / Validation programmes: A Quality Assurance Unit is operating inside the facility. The institution applies Good Laboratory Practices rules according to the EU. The team are available to participate in EU validation programmes.

Sources of financing: Privates

Type of Institution: Industrial (pharmaceutical)

Staff:

Nuria Sales Aragones, Email: rd@uriach.com, D, 80 % time devoted to altern. meth.
Lourdes Conte Visús, Email: rd@uriach.com, Dr, 80 % time devoted to altern. meth.

Total staff involved in alternative methods is 2 people.

Activities / aims: This industrial (pharmaceutical) department is mainly involved in basic research and regulatory testing; it performs pharmacodynamics (in vitro metabolism) testing on a routine basis. Pharmaceuticals are routinely evaluated.

Model systems: The model systems used are in vitro methods: cell-free systems (microsomes and postmitochrondrial fractions).

The endpoint employed in vitro is metabolic activity.

Work lines: The main lines of work are: in vitro metabolism by hepatic rat, dog, monkey and human microsomes; Research of the CYP P-450 involved in the metabolism of different drugs; In vitro investigation of potential inhibitory effects of a drug on CYP P-450.

Quality assurance / Validation programmes: A Quality Assurance Unit is operating inside the facility. The institution applies Good Laboratory Practices rules. The team have previously been involved in the following alternative method validation programmes: Validation for HPLC. They are available to participate in EU validation programmes related to metabolism studies validation.

Type of Institution: Industrial (Cosmetic ingredients. Vegetable extracts)

Staff:

Lourdes Mayordomo, Email: provital@sumi.es, Ld Biología, Directora UTTEC, 100 % time devoted to altern. meth.
Ricardo Armengol, Ld Farmacia, Director Técnico, 10 % time devoted to altern. meth.
Aurora Benaiges, Ld Farmacia, Directora I+D , 30 % time devoted to altern. meth.
Antonia María Gómez, Dr Ciencias Químicas, Responsable de Cultivos Celulares, 70 % time devoted to altern. meth.
Desirée Pérez, Técnico Superior de Análisis Químico, Auxiliar de Laboratorio, 10 % time devoted to altern. meth.
Mónica Puigdellivol, Técnico Especialista, Auxiliar de Laboratorio, 30 % time devoted to altern. meth.

Total staff involved in alternative methods is 6 people.

Activities / aims: This industrial (cosmetic ingredients and vegetable extracts) department is mainly involved in regulatory testing; it performs toxicology (ocular cytotoxicity, dermal irritation and corrosivity) testing on a routine basis, and cell biology and biochemistry studies at a research level. Cosmetics and vegetable extracts are routinely evaluated.

The main use of alternative methods is for screening and replacement test.

Model systems: The model systems used are embryos (chick embryo chorioalantoid membrane assay (HET-CAM)), in vitro methods -- micro-organisms (Salmonella typhimurium), organ culture (bovine corneal opacity / permeability (BCOP)), cell lines culture (foreskin fibroblasts) and cell-free systems (hepatic mitochondria).

The endpoints employed are in vitro morphology (optical microscopy; lesions to blood vessels (CAM), cornea (BCOP)), metabolic activity (LDH, oxygen consumption) and nucleic acids (mutation reversion).

Experimental systems (examples):

1 chick embryo chorioallantoid membrane assay, blood vessel lesions, ocular irritation, replacement test
2 Salmonella typhimurium, mutation reversion, mutagenicity, screening, replacement test
3 hepatic mitochondria, oxygen consumption, metabolic alterations, screening
4 foreskin fibroblasts, LDH activity by spectrophotometry, cytotoxicity, screening, replacement test

Work lines: Provital manufactures ingredients for the cosmetic industry, mainly plant extracts. The aim of the studies is to obtain data on efficacy and safety in order to comply with present legislation. Plant extracts are not included in alternative method validation, and Provital is defining the methods most suited to these products.

Quality assurance / Validation programmes: The team have previously been involved in the following alternative method validation programme: the EC/HO international validation study on alternatives to the Draize eye test. They are available to participate in EU validation programmes.

Sources of financing: Self financing; Ayudas intercambio personal investigador entre industrias y centros públicos de investigación (B); Ayudas I+D para incorporación de doctores a empresas, para cultivos celulares.

Type of Institution: Distributor

Staff:

Jorge Puig Martín, Email: pmasoc@datalogic.es, Ingeniero Químico IQS, Director, 10 % time devoted to altern. meth.

Total staff involved in alternative methods is 1 person.

Activities / aims: This distributor department is mainly involved in commercialization of in vitro tests; it performs toxicology (dermal irritation and corrosivity, immunotoxicity and sensitisation, phototoxicity, hepatotoxicity), cosmetics testing on a routine basis. Cosmetics are routinely evaluated.

The main use of alternative methods is for replacement studies.

Model systems: The model systems used are in vitro methods: culture of explants, reaggregates, reconstituted organs, cell lines culture (hepatocytes, fibroblasts).

The endpoint employed in vitro is cell viability

Experimental systems (examples):

1 rabbit fibroblasts, neutral red uptake, ocular irritation, replacement test
2 human skin explants, dermal irritation, replacement test

Others: The company is the exclusive Spanish distributor of the firm BIOPREDIC (Rennes, France)

Type of Institution: Governmental service facility (diagnostic, control, monitoring)

Staff:

Tesifón Parrón Carreño, Dr Medicina.
Reyes Alvarez Osorio, Dr Medicina.
Rafael Durban, Ld Farmacia.
Jose Luis Serrano Ramirez, Ld Medicina y Cirugía.
Alberto González Ramón, Ld Veterinaria.

Total staff involved in alternative methods is 5 people.

Activities / aims: This governmental service facility department (diagnostic, control, monitoring) is mainly involved in basic research; it performs toxicology (chronic toxicity) testing on a routine basis. Pesticides are routinely evaluated.

The main use of alternative methods is for screening.

Model systems: The model systems used are human volunteers.

The endpoints employed in vivo are conventional analysis, cholinesterase, paranitrophenol, lithium and serotonine.

Work lines: Effects of long term exposure to pesticides in fumigation workers: case control studies. Mutagenesis in fumigation workers. Memory alteration in fumigation workers after acute and chronic exposure.

Type of institution: Industrial (Pharmaceutical)

Staff:

Emilio Díez, Email: emilio_diez@sbphrd.com, Dr Ciencias Químicas, Associate Director, 20 % time devoted to alternative methods.

Total staff involved in alternatives methods is about 15 persons: 9 doctors, 2 Lic, 4 technicians.

Activities / aims: This Industrial (Pharmaceutical) department is mainly involved in basic research, methods development and validation, search and identification of pharmaceutical from vegetal origen; it performs cell biology, biochemistry, biokinetics and biotransformation, and toxicology testing on a routine basis, and toxicology (basal cytotoxicity) studies at a research level. The materials routinely evaluated are pharmaceuticals, diverse chemical compounds, being also occasionally studied.

The main use of alternatives methods is for screening.

Model systems: The model systems used are in vitro methods -- micro-organisms (E. coli, S. aureus, C. albicans, etc), primary culture of dispersed cells (human lymphocytes, monocites, PMS, etc), cell lines culture (mouse, decens of human stable and receptor or enzyme transfected cell lines) and cell-free systems (plasmatic, isolated proteins, recombinant proteins).

The endpoints employed in vitro are cell viability (cellular dehydrogenases by photometry and esterases by fluorimetry), celular proliferation (Tyd uptake, filtration) and cell signalling (cAMP, IPS, intracellular calcium with Fluo3 and Fluo 4).

Experimental systems (examples):

1Bacteria subcellular fractions, lucipherase by luminiscence, identification of new antibiotics, screening
2 Mammal cells, cAMP by radioactivity and SPA scintillation proximity assays, identification of new pharmaceuticals, screening
3 Purified recombinant proteins, diverse enpoints determined by flourescence (TRF, HTRF, FLINT, FP), radiometry, luminiscence, photometry, identification of new pharmaceuticals, screening
4 Mammal cells, cell dehydrogenases by photometry and esterases by fluorimetry, cytotoxicity, screening

Work lines: High troughput screening of pharmaceuticals of vegetal origen.

Quality assurance / Validation programmes: A Quality Assurance Unit is operating inside the facility. The institution applies Good Laboratory Practices rules according to the EU.

Sources of financing: Own financing, CDTI, Becarios del Ministerio de Educación, Plan IDE (Incorporación de Doctores a Empresas) 

Fuente / Source: Guillermo Repetto, Ana del Peso, Manuel Salguero, Manuel Repetto (1999) Inventory of the Spanish Institutions and Scientists Involved in Alternatives to the use of Laboratory Animals (Refinement, Reduction or Replacement) Revista de Toxicología 16: 50-127.