Fertility Disorders and Teratogenicity Caused by Work Place Exposure, 1998

On February 9 and 10, 1998, the Central Federation of the German Accident Insurance Institutions organized the workshop in Hennef (F.R.G.). Fifty experts from basic medical science and related medical disciplines, from the chemical industry, from authorities and administration involved in work safety were invited to discuss this topic. The chair was held by Prof. Rüdiger, Vienna. He opened the meeting with general remarks on the field of reproductive toxicity. Firstly, toxic agents may impair fertility, lactation and the hormonal regulation. Secondly, agents may cause teratogen effects, and thirdly, genotoxicity may occur. However, no proper example for a substance causing genotoxicity is known. The follow-up of pregnancies of parents treated with cytotoxic drugs for a tumor disease did not reveal an increased incidence of neonatal malformations in more than 3,000 cases when compared to the normal population.

Six colleagues initiated the discussion by papers on basic aspects of reproduction, on the estimation of reproductive toxicity of certain compounds, and on the existing and future legal regulations for the classification of compounds as reproductive toxicants.

Holstein (Hamburg) started with a description of the "Organization and regulation of the maturation of gametes" in both sexes. He described the fundamental difference between the maturation of female and male gametes and indicated the different possibilities of damaging effects of toxic agents.
Nieschlag (Münster) summarized the assessment of male fertility and its disorders. He described the clinical investigations, the semen analysis and the assessment of endocrine parameters, and he pointed out that further insights in molecular genetics might improve our knowledge of the mechanisms of male infertility.
Stahlmann (Berlin) reported on the teratogenic effects of industrial compounds. He presented as a model the effects of toluol and related compounds in mice. He emphasized the use of sophisticated methods and comprehensive knowledge of the basic cytological and molecular mechanisms.

Straif (Münster) described the principles of epidemiologic studies in this field. He discussed the advantages and drawbacks of the different study types: prospective cohort studies of exposed and nonexposed person, and retrospective case-control studies. Some examples were presented. Hofmann (Darmstadt) reported on the scientific criteria for the classification of reproductive toxic agents. The compounds should be tested for teratogenicity, for damages to fertility and for genotoxicity in the second generation. Guidelines for the classification of compounds were published by the EC: category 1 comprises compounds with a proven negative influence on fertility, category 2 are compounds, which possibly influence fertility, and category 3 summarizes compounds, for which some evidence for their reproductive toxicity exist. Updating these categories depends on continuous evaluation by experts. The classification is hazard based on the intrinsic properties of the chemicals involving the consideration of reproductive effects seen in humans and effects shown in suitable animal tests. Risk is not taken into account into the classification process.

In the last presentation, Vater (Kassel) summarized the most important legal regulations for work safety. If compounds are classified as reproductive toxic agents according to the categories quoted above, their industrial safety has to be regulated by national regulations and those of the EC. Compounds suspected for reproductive toxicity must not be further used in the industry. They should be substituted by other compounds, or at least the hazard has to be specified.

The workshop closed with a stimulating and partly controversial roundtable discussion by the experts, including also the audience. As a conclusion, all participants agreed that workplace agents are in general not a severe cause of infertility. Since the cause of infertility is unknown in about 50% of the patients asking for help in reproductive medicine, efforts should be made to improve the knowledge in this field. All papers and the roundtable discussion will be published as a BIA report.

Walter Krause, Germany