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Many environmental contaminants disrupt the vertebrate endocrine system. Although they may be no more sensitive to endocrine-disrupting contaminants (EDCs) than other vertebrates, reptiles are good sentinels of exposure to EDCs due to the lability in their sex determination. This is exemplified by a study of alligators at Lake Apopka, Florida, showing that EDCs have altered the balance of reproductive hormones resulting in reproductive dysfunction. Such alterations may be activationally or organizationally induced. Much research emphasizes the former, but a complete understanding of the influence of EDCs in nature can be generated only after consideration of both activational and organizational alterations. The organizational model suggests that a small quantity of an EDC, administered during a specific period of embryonic development, can permanently modify the organization of the reproductive, immune, and nervous systems. Additionally, this model helps explain evolutionary adaptations to naturally occurring estrogenic compounds, such as phytoestrogens. -Environ Health Perspect 103(Suppl 7): 157-164 (1995)

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Many environmental cont ants aer the reproduction of animals by altering the development and function of the edocrine system. The ability of environmental contamints to alter the endocrn s of alligators was studied both in a descriptive study in which juvenile alligators from; a historicallycontaminated lake were compar to anima fro a control lk that aromatase activity is increased in prospective females during periods coinciding with thermosensitivity (11-13). Second, high doses (50-100 pg per egg) of testosterone cause feminization of T scripta at a male-producing temperature (8,14). Because testosterone is the precursor to E2, this phenomenon is thought to be mediated by the enzyme aromatase. Third, administration of an aromatase inhibitor induces male sex determination in both a female unisexual (parthenogenetic) lizard and a turtle with temperature-dependent sex determination (15). Collectively, these studies suggest that aromatase is an enzyme critical to thermosensitive sex determination and is capable of modification by extrinsic factors.In consideration of these studies, we propose that the endocrine-altering effects of some environmental contaminants may be mediated via changes in the expression or activity of the aromatase enzyme. Two studies, one descriptive and one experimental, were conducted to test this hypothesis. First, juvenile alligators from a control lake and a lake historically contaminated with a number of persistent organochlorines were analyzed for plasma steroid hormones and in vitro gonadal-adrenal aromatase activity. Second, embryos from a control lake were exposed to several known hormonal modifiers and two common herbicides, and

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A need is recognized for the development and evaluation of bioassays for detection of thyroid system-disrupting compounds. The issue of testing for thyroid disruption can be addressed by exploiting amphibian metamorphosis as a biological model. In the present study, a test protocol for a Xenopus metamorphosis assay (XEMA) was developed and its interlaboratory transferability was evaluated in an informal ring test with six laboratories participating. In the XEMA test, exposure of Xenopus laevis tadpoles was initiated at stages 48 to 50 and continued for 28 d. Development and growth of tadpoles were assessed by means of developmental stage and whole body length determinations, respectively. For initial test protocol evaluation, thyroxine (T4), and propylthiouracil (PTU) were used as positive controls for thyroid system-modulating activity, and ethylenethiourea (ETU) was used as a test compound. Exposure of tadpoles to 1 microg/L T4 produced a significant acceleration of metamorphosis whereas PTU concentrations of 75 and 100 mg/L completely inhibited metamorphosis. Five different ETU concentrations (5, 10, 25, 50, and 100 mg/L) were tested and a concentration-dependent inhibition of metamorphosis was observed. None of the compounds affected tadpole survival, and only PTU caused a slight retardation in tadpole growth. This study demonstrates that the XEMA test provides a sensitive, robust, and practical testing approach for detection of compounds with both agonistic and antagonistic effects on the thyroid system in Xenopus tadpoles.

Many environmental contaminants disrupt the vertebrate endocrine system. Although they may be no more sensitive to endocrine-disrupting contaminants (EDCs) than other vertebrates, reptiles are good sentinels of exposure to EDCs due to the lability in their sex determination. This is exemplified by a study of alligators at Lake Apopka, Florida, showing that EDCs have altered the balance of reproductive hormones resulting in reproductive dysfunction. Such alterations may be activationally or organizationally induced. Much research emphasizes the former, but a complete understanding of the influence of EDCs in nature can be generated only after consideration of both activational and organizational alterations. The organizational model suggests that a small quantity of an EDC, administered during a specific period of embryonic development, can permanently modify the organization of the reproductive, immune, and nervous systems. Additionally, this model helps explain evolutionary adaptations to naturally occurring estrogenic compounds, such as phytoestrogens.