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The carrying out of clinical trials with a view to the marketing of drugs for human use is directly related to results of some animal studies. This workshop was devoted to evaluation of the quality and interest of these experimental models in reproductive toxicology. The predictive ability of preclinical trials to make extrapolations from animals to man decreases from foetotoxic to tetratogenic risks respectively and from the effects on fertility in both sexes to postnatal risks. As a result of this workshop, we propose the following improvements: (1) standardization and generalization of fertility test evaluations, especially the spermogram, in order to improve animal and human correlations; (2) development of knowledge and standardization of the follow up of the oestral cycle; (3) improvement of standardization, harmonization and diffusion of postnatal tests that prove relevant in animals; (4) increase in initiatives aimed at better mutual understanding of all drug partners; (5) creation of registers for new drugs, as soon as possible during clinical trials, to study their effects on the whole reproductive process; (6) recommendations for the creation of guidelines for International Conference on Harmonisation (ICH) to enable classification of observed effects in experimental models. This could lead to specific (potentially for each phase of the reproductive cycle) guidelines, precautions for use and/or contraindications which are listed in the summary of product characteristics.

Concerned with adapting the withdrawal time to real risks attributed to residues, the authors present a general schema of evaluation based on the metabolism-toxicity relationship. This schema takes into account: a) possible distinction between potentially toxic and atoxic metabolites for extractable residues, b) the more or less large biovailability of residues, c) the methodological evaluation difficulties of toxicity of bound residues. Without neglecting public health, this procedure leads to less constrained restrictions in use of veterinary drugs.

During the past years, many publications and reviews have described kidney and bone lesions observed after human chronic cadmium poisonings of food or occupational origin. In this experiment carried out in rat fed with normal diets or polydeprived of vitamin D3, calcium and proteins, with or without addition of cadmium, the bone lesions observed are as severe in all polydeprived animals, wether treated with cadmium or not.

The injection of alpha-chymotrypsin into the posterior chamber of the eye is known to produce an experimental ocular hypertension of long duration in animals. The present study reports the pathological changes which occur in the eye during the first nine months after the ocular injection of alpha-chymotrypsin in rabbits. Six weeks after treatment most of the eyes showed a buphthalmia and an intraocular pressure elevation which varied greatly from animal to animal. The anterior chamber angle of the treated eyes showed a progressive enlargement. Several days after the enzyme injection a transient increase in thickness of the cornea and Descemet membrane was noted. Cupping of the optic disc, characterized by a total disappearance of the optic nerve head fibers and an excavation beginning at margins of the retina appeared after four months and in most cases were present seven months after the treatment. More or less prominent retinal degeneration was also evidenced three months after enzyme injection. The results indicate alpha-chymotrypsin-induced occular hypertension in the rabbit leads after several months to pathological change in the eye analogous to that observed in human glaucoma.