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DOSE-DEPENDENT TRANSITIONS IN MECHANISMS OF TOXICITY: ZINC CASE EXAMPLE
Citation:
ROGERS, J. M., G. P. DASTON, J. URIU-ADAMS, L. A. HANNA, AND C. L. KEEN. DOSE-DEPENDENT TRANSITIONS IN MECHANISMS OF TOXICITY: ZINC CASE EXAMPLE. Presented at European Toxicology Society (Eurotox), Cavtat / Dubrovnik, CROATIA, September 20 - 24, 2006.
Description:
Zinc (Zn) is an essential trace element. Maternal Zn deficiency can result in complications of pregnancy and inadequate supply of Zn to the conceptus can interfere with the development of numerous organ systems. Maternal dietary Zn deficiency has been shown to be teratogenic in all species tested. In utero Zn deficiency may result from inadequate maternal dietary Zn intake (primary Zn deficiency) or from disturbances in maternal Zn metabolism that decrease availability of Zn to the embryo/fetus (secondary Zn deficiency). Derangement of maternal Zn metabolism induced by chemical exposure is the topic of this presentation. Metallothionein (MT) is a metal-binding protein present in a number of tissues, particularly the liver. Hepatic MT can be induced by exposure to metals or a variety of organic molecules, and MT induction is part of the acute phase response to tissue damage, infection or severe stress. We have demonstrated that a variety of non-metal chemicals can induce a maternal acute phase response including hepatic MT induction. Induction of the acute phase response leads to sequestration of maternal circulating Zn to hepatic MT, reducing maternal serum Zn and therefore Zn availability to the conceptus. Thus, induced (secondary) in utero Zn deficiency can be a significant mode of action for chemicals in standard developmental toxicity bioassays, particularly agents given at or near maternally toxic levels, and may also be important for women with multiple chemical exposures, infections, and/or stress during pregnancy, particularly if their dietary Zn intake is marginal or inadequate. This abstract does not reflect EPA policy.