WRITTEN QUESTION E-0316/03 by Chris Davies (ELDR) to the Commission. Validation studies of non-animal tests.
Date: 2003-02-10
Institutions: European Parliament, Provisional data
Subjects: Joint Research Centre, protection of animals, research method, scientific report, testing

7.11.2003

EN

Official Journal of the European Union

C 268 E/91

In conclusion, no report was overdue on the date of the Commission reply to the written question by the
Honourable Member as far as air quality and waste are concerned. The most important reports were
received for water-related issues.

(1) OJ L 229, 30.8.1980.
(2) OJ L 378, 31.12.1982.
(3) OJ L 87, 27.3.1985.
(4) OJ L 213, 22.8.1996.
(5) OJ L 296, 21.11.1996.
(6) OJ L 163, 29.6.1999.
(7) OJ L 319, 4.12.2001.
(8) OJ L 365, 31.12.1994.
(9) OJ L 67, 7.3.1998.
(10) OJ L 194, 25.7.1975.
(11) OJ L 78, 26.3.1991.
(12) OJ L 377, 31.12.1991.
(13) OJ L 194, 25.7.1975, as amended by Directive 87/101/EEC of 22 December 1986, OJ L 42, 12.2.1987.
(14) OJ L 181, 4.7.1986.
(15) OJ L 365, 31.12.1994.
(16) OJ L 129, 18.5.1976.
(17) OJ L 229, 30.8.1980.
(18) OJ L 31, 5.2.1976.
(19) OJ L 330, 5.12.1998.
(20) OJ L 327, 22.12.2000.

(2003/C 268 E/092)

WRITTEN QUESTION E-0316/03

by Chris Davies (ELDR) to the Commission

(10 February 2003)

Subject: Validation studies of non-animal tests

In July 2002, ECVAM (1) identified the 13 non-animal tests listed below as being technically ready to
complete prevalidation or validation studies by 2003:

(cid:1) Human skin reconstructed skin model;

(cid:1) Skin-integrity function test;

(cid:1) Eye irritation QSAR or ESR;

(cid:1) Acute systemic toxicity QSAR/DEREK;

(cid:1) Biokinetics in vitro screens for metabolism;

(cid:1) Biokinetics human liver cell sandwich culture;

(cid:1) Target organ/system toxicity (neurotoxicity) 3D brain cell cultures and neuroblastoma cell line;

(cid:1) Target organ/neurotocicity Glial and neuronal cell cultures;

(cid:1) Genotoxicity/genotoxic carcinogens in vitro micronucleus test;

(cid:1) Reproductive toxicity (male fertility) Leydig cell line test;

(cid:1) Endocrine disruption cell systems for receptor binding;

(cid:1) Endocrine disruption QSAR to predict receptor binding.

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Official Journal of the European Union

EN

7.11.2003

Can the Commission confirm that a pre-validation or validation study for each of these tests is now under
way? If this is not the case, can the Commission explain why particular studies are delayed and when they
can be expected to begin?

(1) European Centre for the Validation of Alternative Methods, in its report ‘Alternative (Non-animal) Methods for

Chemicals Testing: Current Status and Future Prospects’.

Answer given by Mr Busquin on behalf of the Commission

(27 February 2003)

In July 2002, ECVAM (1) identified the 13 non-animal tests listed below as being technically ready to
complete prevalidation or validation studies by 2003.

The current status is as follows:

(cid:1) human skin reconstructed skin model

(cid:1) skin-integrity function test

On-going validation of reconstructed human epidermis (Epiderm and Episkin). Assays and Skin
integrity function test (SIFT) for acute skin irritation; the project is delayed by the administrative
procedure (call for tender).

(cid:1) acute systemic toxicity other than QSAR/DEREK

In 2002 ECVAM started a joint validation study together with ICCVAM (American Interagency
Coordinating Committee on the Validation of Alternative Methods).

The primary goal of this study is to evaluate the relevance of two basal cytotoxicity assays named the
BALB/c 3T3 Neutral Red Uptake Cytotoxicity Assay and the Normal Human Keratinocyte Neutral Red
Uptake Cytotoxicity Assay for refining and reducing animal use for acute oral toxicity testing.

The study is scheduled to be completed by end 2003 beginning 2004.

(cid:1) Biokinetics in vitro screens for metabolism

Phase I Prevalidation studies using subcellular fractions from human hepatocytes or from genetically
engineered cell lines expressing human genes to determine metabolism-mediated effects are starting in
2003.

Phase II Prevalidation of in vitro models for evaluating the effects of enzyme polymorphism on
metabolism is completed.

(cid:1) Biokinetics human liver cell sandwich culture

Phase II Prevalidation of human liver sandwich cultures for evaluating induction of key biotrans-
formation enzymes is initiated in 2003.

(cid:1) Target organ/system toxicity (neurotoxicity) 3D-brain cell cultures and

Phase I Prevalidation studies using 3D-brain cell cultures (aggregates) are initiated in 2003. The model
has been established.

(cid:1) Neuroblastoma cell line

Currently the model
initiated in 2003.

is evaluated at ECVAM. Phase I Prevalidation of neuroblastoma cell

lines is

(cid:1) Target organ/neurotocicity Glial and neuronal cell cultures

Currently the model is evaluated at ECVAM. Phase I Prevalidation studies using mixed cultures of
neuronal and glial cells are initiated in 2003.

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Official Journal of the European Union

C 268 E/93

(cid:1) Genotoxicity/genotoxic carcinogens in vitro micronucleus test

The test has been extensively used by ECVAMs partners (University Autonoma Barcelone and
University of Pisa) in the context of the contract study on Cell Transformation Assay. The contract
ends this month and a final meeting with such partners will be held in ECVAM on 26 February 2003.
A possible validation will be discussed.

(cid:1) Reproductive toxicity (male fertility) Leydig cell line test

Contract negotiated could not be financed in 2002, foreseen for 2003. To be integrated in a planned
Integrated Project on Reproductive Toxicity managed by ECVAM.

(cid:1) Endocrine disruption cell systems for receptor binding

(cid:1) Endocrine disruption QSAR to predict receptor binding

ECVAM has joined a validation initiative of
Development (OECD), first meeting in March 2003.

the Organisation for Economic Co-operation and

(cid:1) Acute systemic toxicity QSAR/DEREK

(cid:1) Eye irritation QSAR or ESR

Through the joint efforts of the European Chemicals bureau (ECB) and ECVAM, the Joint Research
Centre (JRC) plans to initiate the validation of QSARs for certain endpoints later this year. However,
the detailed planning of QSAR validation studies is currently awaiting discussions at the OECD level
on internationally-recognised acceptability criteria for QSARs.
It is foreseen that there will be a
minimal set of criteria to judge the readiness of QSARs for validation (equivalent to ECVAM’s test
development criteria for the entry of in vitro tests into prevalidation), and a set of additional criteria
that are applied at the end of the QSAR validation process, to judge the scientific validity of QSARs.
Therefore, the QSARs selected for validation will need to take account of certain acceptability criteria.
For this reason,
it is likely that the time-frame for the validation of QSARs will be revised in
accordance with an in-depth evaluation of specific QSARs, which was not performed during the
preparation of the ECVAM report.

(1) European Centre for the Validation of Alternative Methods, in its report ‘Alternative (Non-animal) Methods for

Chemicals Testing: Current Status and Future Prospects’.

(2003/C 268 E/093)

WRITTEN QUESTION P-0322/03

by Karla Peijs (PPE-DE) to the Commission

(4 February 2003)

Subject: Guyana Shield Initiative

Is the Commission aware of the importance of the Guyana Shield for the conservation of the global
biodiversity, its importance as a global CO2 sink and as one of the major freshwater reservoirs in the
world, and its importance for the many indigenous peoples living in this area?

The EU is a party to the international environmental treaties like the Biodiversity Convention, the Climate
Change Treaty and the Desertification Convention and therefore bound to implement the objectives of
these conventions. Its Water Initiative has become a central element in the programme for sustainable
development. The Guyana Shield is one of the most important regions of the world with regard to these
objectives. Taking these objectives into account, what measures has the Commission taken to safeguard the
natural and environmental values of the Guyana Shield for posterity?

What are the objectives of the ACP and ALA development aid programmes for the Guyana Shield
countries and what activities with regard to safeguarding the natural and environmental values of these
countries are financed by these programmes?