This particularly applies (pursuant to Directive 86/609/EEC)(3) to animal experiments involving species which are closest to human beings.

However, to date, no particular malformative effect has been reported. No teratogenic effect has been observed in animal studies.

Animal studies as well as in vitro experiments with human hepatic microsomes indicated that ritonavir primarily underwent oxidative metabolism.

any restriction on the extent to which an experimental animal can satisfy its physiological and ethological needs shall be limited to the absolute minimum;

The recommended use in human subjects is based primarily on in vitro susceptibility and on animal experimental data together with limited human data.

for viruses and viroids test for infectivity carried out by bio assay or on a suitable cell culture at least seven days after administration to test animals

Data on photomutagenicity/ photocarcinogenicity show a weak photomutagenic or phototumorigenic effect of ciprofloxacin in-vitro and in animal experiments.

The validation of alternative methods for animal testing will increase in importance in support of the new testing programme of the new chemicals policy.

specific animal health requirements, for imports into the Community, and the nature and content of accompanying documents for animals intended for zoos, circuses, amusement parks or experimental laboratories, according to the species;

The test substance is orally administered daily in graduated doses to several groups of experimental animals, one dose level per group for a period of 28 days.

The Commission has proposed a Directive amending for the seventh time Directive 76/768/EEC in order to solve definitively the issue of experiments on animals in the cosmetic products sector.

'Furthermore, any reference to testing on animals must state clearly whether the tests carried out involved the finished product and/or its ingredients.';

In particular, Article 7 of that Directive requires that animal experiments be replaced by alternative methods, when such methods exist and are scientifically satisfactory.

5 No data on acute toxicity of Puregon in humans is available, but the acute toxicity of Puregon and of urinary gonadotrophin preparations in animal studies has been shown to be very low.

However, these provisions concern only alternative methods which do not use animals and they do not take account of alternative methods developed in order to reduce the number of animals used for experiments or to reduce their suffering.

No data on acute toxicity of Fertavid in humans is available, but the acute toxicity of Fertavid and of urinary gonadotrophin preparations in animal studies has been shown to be very low.

In accordance with the Amsterdam protocol on animal protection and welfare, animal experiments must be replaced with alternatives wherever possible.

Experimental animal studies are insufficient to assess the safety with respect to reproduction, development of the embryo or foetus, the course of gestation and peri- and postnatal development.

Experiments on animals indicate that there is a narrow margin between the behaviourally active and lethal dose of PMMA and therefore a high risk of acute toxicity exists.

An experiment shall not be performed if another scientifically satisfactory method of obtaining the result sought, not entailing the use of an animal, is reasonably and practicably available.

The Commission shall present an annual report to the European Parliament and the Council on progress in the development, validation and legal acceptance of alternative methods to those involving experiments on animals.

As far as possible attempts should be made to select laboratory animals which may be expected to metabolize the additive in a similar way to man.

If, however, systemic absorption is demonstrated during therapeutic experimentation, toxicity tests shall be carried out on animals, including where necessary, foetal toxicity tests.

Commission Directive 2000/41/EC of 19 June 2000 postponing for a second time the date after which animal tests are prohibited for ingredients or combinations of ingredients of cosmetic products

Whereas there exist between the national laws at present in force for the protection of animals used for certain experimental purposes disparities which may affect the functioning of the common market;

Bexarotene, in common with the majority of retinoids, was teratogenic and embryotoxic in an animal test species at systemic exposures that are achievable clinically in humans.

If practical experience shows the substances and preparations to be capable of inducing a sensitization reaction in a substantial number of persons by skin contact, or on the basis of a positive response in experimental animals.

Each batch of the feedingstuffs used in the experimental studies on animals must be analysed for the concentration of the relevant active substances using an appropriate method and a report of the analytical results must be provided.

However, in view of the complexities involved in these tests and the very large number of animals necessary, particularly for the specific locus test, a strong justification is needed before undertaking these studies.

Recalling that the aim of the Council of Europe is to achieve a greater unity between its members and that it wishes to cooperate with other States in the protection of live animals used for experimental and other scientific purposes;

The Committee expressed the opinion(8) that the effects of the substance detected in test animals on porphyrin levels are relevant for humans but saw no evidence that humans are more sensitive to the effect than animals.

NSAIDs Animal trials have shown that the concurrent administration of very high doses of fluoroquinolones and certain NSAIDs (but not acetylsalicylic acid) may provoke convulsions.

A study on Rhesus-monkeys that were exposed to anthrax by inhalation revealed that 8/ 9 animals survived the experiment when these animals were treated from 1 day after anthrax exposure with ciprofloxacin twice daily for a period of 30 days.

Whereas in the conditions governing approval of bodies, institutes or centres, references should be made, if they keep animals intended for experimental laboratories, to Council Directive 86/609/EEC of 24 November 1986 on the approximation of laws, regulations and administrative provisions of the Member States regarding the protection of animals used for experimental and other scientific purposes (2), in order to align these conditions in the Community and for third countries;

Commission Directive 2000/41/EC of 19 June 2000 postponing for a second time the date after which animal tests are prohibited for ingredients or combinations of ingredients of cosmetic products (OJ L 145, 20.6.2000, p. 25)."

This applies especially for animal protection which requires that the number of experiments on animals be restricted in accordance with Council Directive 86/609/EEC of 24 November 1986 on the approximation of laws, regulations and administrative provisions of the Member States regarding the protection of animals used for experimental and other scientific purposes(5).

On the basis of requests for authorization and notifications received, and on the basis of the reports made, the authority in each Member State shall collect, and as far as possible periodically make publicly available, the statistical information on the use of animals in experiments in respect of:

Newly generated data from conventional toxicological and/or pathological experiments on laboratory animals are normally required unless the applicant can justify, on the basis of the previous information, that the use of the micro-organism, under the proposed conditions of use, does not have any harmful effects on human and animal health.

Commission Directive 2000/41/EC of 19 June 2000 postponing for a second time the date after which animal tests are prohibited for ingredients or combinations of ingredients of cosmetic products(3) is to incorporated into the Agreement,

whereas, therefore, this Directive makes use of the results of assessments of toxicological and ecotoxicological properties only when these are already known and entails no obligation to conduct further experiments on animals;

In accordance with Directive 86/609/EEC and with Directive 93/35/EEC, it is essential that the aim of abolishing animal experiments for testing cosmetic products be pursued and that the prohibition of such experiments becomes effective in the territory of the Member States.

The biological examinations mentioned under point 2.3.1 should be carried out preferably on asmall satellite group of animals (a group separated from and dependent upon the main group) atappropriate intervals throughout the experiment and on the surviving animals at the end of theexperiment.

whereas Article 7(2) of that Directive stipulates that an experiment shall not be performed if another scientifically satisfactory method of obtaining the results sought, not entailing the use of an animal, is reasonably and practically available;

Member States shall also ensure that all tests on animals are conducted in accordance with Council Directive 86/609/EEC of 24 November 1986 on the approximation of laws, regulation and administrative provisions of the Member States regarding the protection of animals for experimental and other scientific purposes(1).

Whereas assessment of the safety of use of the ingredients employed in cosmetics and of the final product should take account of the requirements of Directive 86/609/EEC (5), which concerns the protection of animals used for experimental and other scientific purposes, and in particular Article 7 (2) thereof;

A series of mouse bioassay procedures, differing in the test portion (hepatopancreas or whole body) and in the solvents used for the extraction and purification steps, can be used for detection of the toxins mentioned in Article 1.

Whereas resources devoted to the conduct of tests on vertebrate animals should not be dissipated as a result of the differences in the laws of the Member States and whereas considerations of public interest and Council Directive 86/609/EEC of 24 November 1986 on the approximation of laws, regulations and administrative provisions of the Member States regarding the protection of animals used for experimental and other scientific purposes (4) militate against needless repetition of tests on animals;

If the proposed experiments or tests referred to in paragraphs 1 and 2 are liable to have harmful effects on human or animal health or to have an unacceptable adverse influence on the environment, the Member State concerned may either prohibit them or only allow them subject to such conditions as it considers necessary to prevent those consequences.

whereas such harmonization should ensure that the number of animals used for experimental or other scientific purposes is reduced to a minimum, that such animals are adequately cared for, that no pain, suffering, distress or lasting harm are inflicted unnecessarily and ensure that, where unavoidable, these shall be kept to the minimum;

Member States shall also ensure that all tests on animals are conducted in accordance with Council Directive 86/609/EEC of 24 November 1986 on the approximation of laws, regulation and administrative provisions of the Member States regarding the protection of animals for experimental and other scientific purposes.