title: Problems in testing and risk assessment of endocrine disrupting chemicals with regard to developmental toxicology.
abstract: Endocrine disrupting chemicals (EDCs) may affect mammalian development either indirectly (by impairing implantation, placental development, lactation, etc.) or directly, altering the maturation of target tissues. Current regulatory tests for reproductive/developmental toxicity should be carefully evaluated with regard to risk assessment of EDCs, considering hazard identification (are relevant endpoints being assessed?) and dose-response assessment (are sensitive NOEL/dose-response curves being provided?). Many in vitro and in vivo assays for sex steroid disruption are available; provided that the metabolic capacities of the assays are defined, they could be integrated in a sensitive battery for early detection of steroid-disrupting potentials. The screening battery should address further regulatory in vivo tests (e.g. what specific parameters have to be investigated). As regards dose-response, qualitative differences may be observed between lower and higher exposures, showing primary hormone-related effects and frank embryotoxicity, respectively. Other problems concern (a) the identification of critical developmental windows, according to hormone concentrations and/or receptor levels in the developing target tissues; (b) the potential for interactions between chemicals with common mechanism/target (e.g. xenoestrogens); (c) most important, besides sex steroids more attention should be given to other mechanisms of endocrine disruption, e.g., thyroid effects, which can be highly relevant to prenatal and postnatal development.
authors.affiliation: Laboratory of Comparative Toxicology and Ecotoxicology, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Mantovani
authors.forename: A V
authors.initials: AV
authors.lastname: Stazi
authors.forename: C
authors.initials: C
authors.lastname: Macrì
authors.forename: F
authors.initials: F
authors.lastname: Maranghi
authors.forename: C
authors.initials: C
authors.lastname: Ricciardi
mesh_terms: D000818:Animals; D015509:Developmental Biology; D004702:Endocrine Glands / Q000187:drug effects*; D004700:Endocrine System Diseases / Q000139:chemically induced* / Q000453:epidemiology*; D004784:Environmental Monitoring; D004785:Environmental Pollutants / Q000633:toxicity*; D062665:Epidemiological Monitoring; D005260:Female; D006801:Humans; D011247:Pregnancy; D018570:Risk Assessment; D013723:Teratogens / Q000633:toxicity*
chemical_list: D004785:Environmental Pollutants; D013723:Teratogens