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11 Screening and Monitoring
Pages 296-310

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From page 296...
... In vivo assays are often unsuitable for large-scale screening because of their relatively high cost, low sensitivity, and labor intensiveness. Moreover, in vivo assays that assess highly complex responses can be modulated through other mechanisms and, therefore, might not be selective for the substances of interest.
From page 297...
... The methods available to screen for HAAs include biologic and instrumental chemical analyses. The former category includes assays that can be used to screen for potential hormonal activity in individual compounds, formulations, or environmental extracts.
From page 298...
... (1998) evaluated the relative binding affinities of 60 estrogenic compounds to the two ER subtypes and found that only a few compounds exhibited major differences in binding affinity to ERa and ERp.
From page 299...
... 299 Cal Cq Cq ˘ .> _.
From page 300...
... This measurement can be done in vitro by using established cell lines derived from estrogen-responsive target organs, including rat pituitary cells and several human breast cancer cell lines, such as MCF7 and T47-D cells. MCF7 cells have been used extensively to screen for estrogen agonists and antagonists (Welshons et al.
From page 301...
... Most in vitro tests are based either on a cellular response, such as cell proliferation, or on gene expression. Historically, the understanding of steroid or thyroid hormonal function has been based on the genomic theory that hormones function through regulation of nuclear transcription complexes by intracellular steroid-binding proteins.
From page 302...
... For example, o,p'-DDT shows little binding to estrogen-binding plasma proteins (Skalsky and Guthrie 1978) , a factor that will increase the effective free fraction of o,p'-DDT in vivo relative to estradiol (Nagel et al.
From page 303...
... Measures of estrogenic activity include vaginal cornification, vaginal epithelial-cell proliferation and tetrazolium reduction, vaginal opening, vaginotrophic response, uterine fluid imbibition, uterotrophic response, uterine glycogen deposition, and uterine estrogen-withdrawal bleeding. In the vaginal-cornification assay (Allen and Doisy 1923)
From page 304...
... 304 lo' ca ca .~ Cal Cq Cq ˘ C)
From page 306...
... Functional biologic markers include population-level responses, changes in secondary-sex characteristics, changes in concentrations of plasma steroid hormones, ex vivo responses, changes in enzyme activity, histologic changes in endocrine-responsive tissues, vitellogenin response, and zona-radiata-protein response. Population-Level Responses and Secondary Sex Characteristics There is no specific end point or group of end points that can be used exclusively to monitor exposure to HAAs and the effects of HAAs.
From page 307...
... . Changes in secondary sexual characteristics occurred at exposures that also caused significant histologic effects but at concentrations that were less than those required to cause significant decreases in fecundity.
From page 308...
... Although exogenous estrogen agonists have minimal effects on plasma vitellogenin in female fish, male fish express low to nondetectable concentrations of the protein, which is readily induced by estrogenic compounds and secreted into plasma. Exposure to environmental estrogens has been shown to induce production of vitellogenin in the blood plasma of male fish (Jobling et al.
From page 309...
... In any case, it should always be recalled that a host of compounds with no hormonal activity can disrupt reproductive and other organismic functions.
From page 310...
... Studies of caged, pinioned, or telemetered animals could provide information about the location, duration, and magnitude of exposure, which could be used to interpret the results of field studies. Dose-response characteristics of recognized actions of various HAAs should be further investigated in in vitro and in vivo studies using concentrations found in the environment.


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