Influence of maternal toxicity on the outcome of developmental toxicity studies.
Paumgartten FJ. J Toxicol Environ Health A. 2010 Jan;73(13-14):944-51.
Laboratorio de Toxicologia Ambiental, Departamento de Ciencias Biologicas, Escola Nacional de Saude Publica, FIOCRUZ, Rio de Janeiro, Brasil. paum@ensp.fiocruz.br
Laboratorio de Toxicologia Ambiental, Departamento de Ciencias Biologicas, Escola Nacional de Saude Publica, FIOCRUZ, Rio de Janeiro, Brasil. paum@ensp.fiocruz.br
Abstract
The relevance of fetal abnormalities noted at maternally toxic doses is a long-standing issue regarding the interpretation of findings of segment II studies. A number of diseases and conditions during pregnancy are known to adversely affect embryo/fetal development, and along this line many scientists believe that any marked disturbance of maternal homeostasis produced by chemical exposure may eventually produce a teratogenic effect.
Although there is little doubt that developmental toxicity may be maternally mediated, the notion that, in principle, any maternal toxicity leads to birth defects is disputed. When embryotoxicity is noted only within the maternally toxic dose range, it is not possible to ascertain whether it is in fact maternally mediated or not (i.e., embryo development may have been impaired by a direct action of the chemical at doses that also adversely affect the mother; in these circumstances it would still be a selective developmental toxicant). However, currently, a chemical is not regarded as a "developmental toxicant" (or "teratogenic agent") if embryotoxicity is apparent only at doses that are also toxic to the mother. In the European Union, developmental hazard identification exerts a strong influence on the classification and labeling of chemicals.
In Brazil, registration of any pesticide that proved to be teratogenic in animal studies is strictly forbidden by law (Pesticide Law, Federal Law 7.802, 1989). Therefore, interpretation of findings from developmental toxicity studies in light of maternal toxicity is particularly relevant to regulatory agencies, and becomes even more important when labeling or cutoff decision-making criteria are adopted regarding teratogenicity.
PMID: 20563928 [PubMed - in process]
