@article{rider_hartig_cardon_lambright_bobseine_guillette_gray_wilson_2010, title={Differences in sensitivity but not selectivity of xenoestrogen binding to alligator versus human estrogen receptor alpha}, volume={29}, number={9}, journal={Environmental Toxicology and Chemistry}, author={Rider, C. V. and Hartig, P. C. and Cardon, M. C. and Lambright, C. R. and Bobseine, K. L. and Guillette, L. J. and Gray, L. E. and Wilson, V. S.}, year={2010}, pages={2064–2071} }
 @article{rider_hartig_cardon_wilson_2009, title={COMPARISON OF CHEMICAL BINDING TO RECOMBINANT FATHEAD MINNOW AND HUMAN ESTROGEN RECEPTORS ALPHA IN WHOLE CELL AND CELL-FREE BINDING ASSAYS}, volume={28}, ISSN={["1552-8618"]}, DOI={10.1897/09-018.1}, abstractNote={Little evidence shows in vivo effects of phthalates on reproductive endpoints in fish. While most of the evidence is negative [ 24,25 ], a few studies report in vivo effects of phthalates on estrogen‐dependent endpoints. Christiansen et al. found that BBP, but not DBP, induced vitellogenin in rainbow trout at concentrations of 500 and 1,000 mg/kg administered via intraperitoneal injection [ 26 ]. Kim et al. found that DEHP elicited potentially antiestrogenic effects in female medaka, as evidenced by decreased vitellogenin levels, decreased gonadal‐somatic indices, and immature oocytes in DEHP‐treated females as compared to their control counter‐parts [ 27 ].}, number={10}, journal={ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY}, author={Rider, Cynthia V. and Hartig, Phillip C. and Cardon, Mary C. and Wilson, Vickie S.}, year={2009}, month={Oct}, pages={2175–2181} }
 @article{rider_wilson_howdeshell_hotchkiss_furr_lambright_gray_2009, title={Cumulative Effects of In Utero Administration of Mixtures of "Antiandrogens" on Male Rat Reproductive Development}, volume={37}, ISSN={["1533-1601"]}, DOI={10.1177/0192623308329478}, abstractNote={ Although risk assessments are typically conducted on a chemical-by-chemical basis, the 1996 Food Quality Protection Act (FQPA) required the Environmental Protection Agency (EPA) to consider cumulative risk of chemicals that act via a common mechanism of toxicity. To this end, we are conducting studies with mixtures to provide a framework for assessing the cumulative effects of “antiandrogenic” chemicals. Rats were dosed during pregnancy with antiandrogens singly or in pairs at dosage levels equivalent to about one half of the ED50 for hypospadias or epididymal agenesis. The pairs include: AR antagonists (vinclozolin plus procymidone), phthalate esters (DBP plus BBP and DEHP plus DBP), a phthalate ester plus an AR antagonist (DBP plus procymidone), and linuron plus BBP. We predicted that each chemical by itself would induce few malformations; however, by mixing any two chemicals together, about 50% of the males would be malformed. All binary combinations produced cumulative, dose-additive effects on the androgen-dependent tissues. We also conducted a mixture study combining seven “antiandrogens” together. These chemicals elicit antiandrogenic effects at two different sites in the androgen signaling pathway (i.e., AR antagonist or inhibition of androgen synthesis). In this study, the complex mixture behaved in a dose-additive manner. Our results indicate that compounds that act by disparate mechanisms of toxicity display cumulative, dose-additive effects when present in combination. }, number={1}, journal={TOXICOLOGIC PATHOLOGY}, author={Rider, Cynthia V. and Wilson, Vickie S. and Howdeshell, Kembra L. and Hotchkiss, Andrew K. and Furr, Johnathan R. and Lambright, Christy R. and Gray, L. Earl, Jr.}, year={2009}, month={Jan}, pages={100–113} }
 @article{blystone_lambright_cardon_furr_rider_hartig_wilson_gray_2009, title={Cumulative and Antagonistic Effects of a Mixture of the Antiandrogens Vinclozolin and Iprodione in the Pubertal Male Rat}, volume={111}, ISSN={["1096-0929"]}, DOI={10.1093/toxsci/kfp137}, abstractNote={Vinclozolin and iprodione are dicarboximide fungicides that display antiandrogenic effects in the male rat, which suggests that a mixture would lead to cumulative effects on androgen-sensitive end points. Iprodione is a steroid synthesis inhibitor, but androgen receptor antagonist activity, which is displayed by vinclozolin, has not been fully evaluated. Here, we demonstrate that iprodione binds to the human androgen receptor (IC(50) = 86.0 microM), reduces androgen-dependent gene expression, and reduces androgen-sensitive tissue weights in castrated male rats (Hershberger assay). Since vinclozolin and iprodione affect common targets in the pubertal male rat, we tested the hypothesis that a mixture would have cumulative antiandrogenic effects. An iprodione dose, that does not significantly affect androgen-dependent morphological end points, was combined with vinclozolin doses (2 x 5 factorial design). Sprague-Dawley rats were dosed by gavage with vinclozolin at 0, 10, 30, 60, and 100 mg/kg/day with and without 50 mg iprodione/kg/day from postnatal day (PND) 23 to 55-57 (n = 8 per group). The age at puberty (preputial separation [PPS]), organ weights, serum hormones, and ex vivo testis steroid hormone production were measured. Vinclozolin delayed PPS, reduced androgen-sensitive organ weights, and increased serum testosterone. The addition of iprodione enhanced the vinclozolin inhibition of PPS (PND 47.5 vs.49.1; two-way ANOVA: iprodione main effect p = 0.0002). The dose response for several reproductive and nonreproductive organ weights was affected in a cumulative manner. In contrast, iprodione antagonized the vinclozolin-induced increase in serum testosterone. These results demonstrate that these fungicides interact on common targets in a tissue-specific manner when coadministered to the pubertal male rat.}, number={1}, journal={TOXICOLOGICAL SCIENCES}, author={Blystone, Chad R. and Lambright, Christy S. and Cardon, Mary C. and Furr, Johnathan and Rider, Cynthia V. and Hartig, Phillip C. and Wilson, Vickie S. and Gray, Leon E., Jr.}, year={2009}, month={Sep}, pages={179–188} }
 @article{rider_hartig_cardon_wilson_2009, title={Development of a competitive binding assay system with recombinant estrogen receptors from multiple species}, volume={184}, ISSN={["1879-3169"]}, DOI={10.1016/j.toxlet.2008.10.015}, abstractNote={In the current study, we developed a new system using full-length recombinant baculovirus-expressed estrogen receptors which allows for direct comparison of binding across species. Estrogen receptors representing five vertebrate classes were compared: human estrogen receptor alpha (hERalpha), quail estrogen receptor alpha (qERalpha), alligator estrogen receptor alpha (aERalpha), salamander estrogen receptor alpha (sERalpha), and fathead minnow estrogen receptor alpha (fhERalpha). Saturation binding analyses indicated 17beta-estradiol (E2) dissociation constants (Kd) were 0.22+/-0.02nM for hERalpha, 0.28+/-0.04nM for sERalpha, 0.44+/-0.04nM for aERalpha, 0.58+/-0.10nM for qERalpha, and 0.58+/-0.05nM for fhERalpha. Binding specificity to each of the receptors was evaluated using E2, dihydrotestosterone (DHT), corticosterone (C), and ethinylestradiol (EE). E2 and EE were strong binders in all species with IC50's ranging from 0.65nM with hERalpha to 1.01nM with sERalpha for E2 and from 0.68nM with sERalpha to 1.20nM with qERalpha for EE. DHT was a weak binder with IC50's ranging from 3.3microM with hERalpha to 39microM with fhERalpha, and C did not bind any of the receptors at concentrations up to 100microM. This system provides a convenient in vitro approach for directly comparing chemical binding to estrogen receptors across multiple species without the need to sacrifice animals.}, number={2}, journal={TOXICOLOGY LETTERS}, author={Rider, Cynthia V. and Hartig, Phillip C. and Cardon, Mary C. and Wilson, Vickie S.}, year={2009}, month={Jan}, pages={85–89} }
 @article{howdeshell_wilson_furr_lambright_rider_blystone_hotchkiss_gray_2008, title={A mixture of five phthalate esters inhibits fetal testicular testosterone production in the sprague-dawley rat in a cumulative, dose-additive manner}, volume={105}, ISSN={["1096-6080"]}, DOI={10.1093/toxsci/kfn077}, abstractNote={Phthalate diesters are chemicals to which humans are ubiquitously exposed. Exposure to certain phthalates during sexual differentiation causes reproductive tract malformations in male rats. In the fetal rat, exposure to the phthalates benzylbutyl phthalate (BBP), di(n)butyl phthalate (DBP), and diethylhexyl phthalate (DEHP) decreases testicular testosterone production and insulin-like 3 hormone mRNA levels. We characterized the dose-response effects of six individual phthalates (BBP, DBP, DEHP, diethyl phthalate [DEP], diisobutyl phthalate [DiBP], and dipentyl phthalate [DPP]) on gestation day (GD) 18 testicular testosterone production following exposure of Sprague-Dawley rats on GD 8-18. BBP, DBP, DEHP, and DiBP were equipotent (ED50 of 440 +/- 16 mg/kg/day), DPP was about threefold more potent (ED50 = 130 mg/kg/day) and DEP had no effect on fetal testosterone production. We hypothesized that coadministration of these five antiandrogenic phthalates would reduce testosterone production in a dose-additive fashion because they act via a common mode of toxicity. In a second study, dams were dosed at 100, 80, 60, 40, 20, 10, 5, or 0% of the mixture. The top dose contained 1300 mg of total phthalates/kg/day including BBP, DBP, DEHP, DiBP (300 mg/kg/day per chemical), and DPP (100 mg DPP/kg/day). This mixture ratio was selected such that each phthalate would contribute equally to the reduction in testosterone. As hypothesized, testosterone production was reduced in a dose-additive manner. Several of the individual phthalates and the mixture also induced fetal mortality, due to pregnancy loss. These data demonstrate that individual phthalates with a similar mechanism of action can elicit cumulative, dose additive effects on fetal testosterone production and pregnancy when administered as a mixture.}, number={1}, journal={TOXICOLOGICAL SCIENCES}, author={Howdeshell, Kembra L. and Wilson, Vickie S. and Furr, Johnathan and Lambright, Christy R. and Rider, Cynthia V. and Blystone, Chad R. and Hotchkiss, Andrew K. and Gray, Leon Earl, Jr.}, year={2008}, month={Sep}, pages={153–165} }
 @article{rider_furr_wilson_gray_2008, title={A mixture of seven antiandrogens induces reproductive malformations in rats}, volume={31}, ISSN={["1365-2605"]}, DOI={10.1111/j.1365-2605.2007.00859.x}, abstractNote={Summary}, number={2}, journal={INTERNATIONAL JOURNAL OF ANDROLOGY}, author={Rider, Cynthia V. and Furr, Johnathan and Wilson, Vickie S. and Gray, L. Earl, Jr.}, year={2008}, month={Apr}, pages={249–262} }
 @article{wilson_blystone_hotchkiss_rider_gray_2008, title={Diverse mechanisms of anti-androgen action: impact on male rat reproductive tract development}, volume={31}, ISSN={["1365-2605"]}, DOI={10.1111/j.1365-2605.2007.00861.x}, abstractNote={Summary}, number={2}, journal={INTERNATIONAL JOURNAL OF ANDROLOGY}, author={Wilson, Vickie S. and Blystone, Chad R. and Hotchkiss, Andrew K. and Rider, Cynthia V. and Gray, L. Earl, Jr.}, year={2008}, month={Apr}, pages={178–185} }
 @inproceedings{howdeshell_rider_wilson_gray_2008, title={Mechanisms of action of phthalate esters, individually and in combination, to induce abnormal reproductive development in male laboratory rats}, volume={108}, number={2}, booktitle={Environmental Research (New York, N.Y.)}, author={Howdeshell, K. L. and Rider, C. V. and Wilson, V. S. and Gray, L. E.}, year={2008}, pages={168–176} }
 @article{howdeshell_furr_lambright_rider_wilson_gray_2007, title={Cumulative effects of dibutyl phthalate and diethylhexyl phthalate on male rat reproductive tract development: Altered fetal steroid hormones and genes}, volume={99}, ISSN={["1096-6080"]}, DOI={10.1093/toxsci/kfm069}, abstractNote={Exposure to plasticizers di(n-butyl) phthalate (DBP) and diethylhexyl phthalate (DEHP) during sexual differentiation causes male reproductive tract malformations in rats and rabbits. In the fetal male rat, these two phthalate esters decrease testosterone (T) production and insulin-like peptide 3 (insl3) gene expression, a hormone critical for gubernacular ligament development. We hypothesized that coadministered DBP and DEHP would act in a cumulative dose-additive fashion to induce reproductive malformations, inhibit fetal steroid hormone production, and suppress the expression of insl3 and genes responsible for steroid production. Pregnant Sprague Dawley rats were gavaged on gestation days (GD) 14-18 with vehicle control, 500 mg/kg DBP, 500 mg/kg DEHP, or a combination of DBP and DEHP (500 mg/kg each chemical; DBP+DEHP); the dose of each individual phthalate was one-half of the effective dose predicted to cause a 50% incidence of epididymal agenesis. In experiment one, adult male offspring were necropsied, and reproductive malformations and androgen-dependent organ weights were recorded. In experiment two, GD18 testes were incubated for T production and processed for gene expression by quantitative real-time PCR. The DBP+DEHP dose increased the incidence of many reproductive malformations by >or=50%, including epididymal agenesis, and reduced androgen-dependent organ weights in cumulative, dose-additive manner. Fetal T and expression of insl3 and cyp11a were cumulatively decreased by the DBP+DEHP dose. These data indicate that individual phthalates with a similar mechanism of action, but with different active metabolites (monobutyl phthalate versus monoethylhexyl phthalate), can elicit dose-additive effects when administered as a mixture.}, number={1}, journal={TOXICOLOGICAL SCIENCES}, author={Howdeshell, Kembra L. and Furr, Johnathan and Lambright, Christy R. and Rider, Cynthia V. and Wilson, Vickie S. and Gray, L. Earl, Jr.}, year={2007}, month={Sep}, pages={190–202} }
 @article{gorr_rider_wang_olmstead_leblanc_2006, title={A candidate juvenoid hormone receptor cis-element in the Daphnia magna hb2 hemoglobin gene promoter}, volume={247}, ISSN={["0303-7207"]}, DOI={10.1016/j.mce.2005.11.022}, abstractNote={Hemoglobin levels are significantly elevated in the crustacean Daphnia magna by juvenoid hormones. The present study was undertaken to identify the specific globin (hb) genes that are induced by juvenoids and to identify putative juvenoid response elements (JREs) that may mediate this induction. Gene product of globin 2 (hb2), but not globin 1 and globin 3, was robustly elevated following juvenoid treatment of daphnids. A candidate JRE, located in the promoter of hb2, bound activated factor(s) in response to juvenoid treatment of daphnids. This hormone-induced protein:JRE interaction was robust when daphnids were reared at high oxygen tension but was inhibited when daphnids were reared under low pO2, implying that hypoxia might act to disrupt juvenoid-mediated endocrine signaling. The candidate JRE consists of a steroid/retinoid-response element-like core adjacent to a 5′ AT-rich extension and thus bears resemblance to response elements that bind monomeric nuclear receptors. The induction of hb2 mRNA levels by juvenoid treatment occurred rapidly (within 4 h of exposure) and was not attenuated by treatment of daphnids with cycloheximide. In contrast, cycloheximide treatment did block hormone-mediated elevations in hemoglobin protein levels. Thus, induction of hb2 by juvenoids was not dependent upon the synthesis of secondary transcription factors that bound the JRE but was likely due to activation of the gene directly by the juvenoid-receptor complex. Affinity pull-down experiments with nuclear proteins extracted from juvenoid-treated daphnids using the JRE as bait yielded a 52 kDa candidate for a monomeric nuclear receptor in D. magna that may mediate the regulatory activity of juvenoids.}, number={1-2}, journal={MOLECULAR AND CELLULAR ENDOCRINOLOGY}, author={Gorr, TA and Rider, CV and Wang, HY and Olmstead, AW and LeBlanc, GA}, year={2006}, month={Mar}, pages={91–102} }
 @article{rider_leblanc_2006, title={Atrazine stimulates hemoglobin accumulation in Daphnia magna: Is it hormonal or hypoxic?}, volume={93}, ISSN={["1096-6080"]}, DOI={10.1093/toxsci/kfl067}, abstractNote={Hemoglobin accumulation in daphnids is an important adaptive response that is regulated by at least two distinct molecular pathways: an endocrine pathway stimulated by terpenoid hormones and an oxygen-sensing pathway involving the hypoxia-inducible factor. We found that the herbicide atrazine elevated hemoglobin levels in Daphnia magna and hypothesized that atrazine induced hemoglobin in daphnids through the hormonal regulatory pathway. This hypothesis was tested by modeling the combined effects of atrazine and the terpenoid hormone mimic pyriproxyfen on hemoglobin mRNA levels assuming the same mechanism of action (concentration addition model) and alternatively, assuming different mechanisms of action (response addition model). Model predictions were then compared to experimental assessments of the combined action of these two chemicals on hemoglobin mRNA levels. Changes in hemoglobin expression were evaluated using real-time RT PCR with primers specific to each of three D magna hemoglobin genes (dhb1, dhb2, and dhb3). Both atrazine and pyriproxyfen significantly elevated levels of the hb2 gene product, while having little effect on hb1 and hb3 gene products. Induction of dhb2 by combinations of atrazine and pyriproxyfen did not conform to the concentration addition predictions. Rather, dhb2 induction by these binary combinations was highly consistent with response addition model predictions. These results indicate that atrazine does not induce hemoglobin through the terpenoid hormone-signaling pathway. Results from this study demonstrate that mixtures modeling can be used to assess a chemical's mechanism of action and that atrazine likely stimulates hemoglobin accumulation through the oxygen-sensing pathway.}, number={2}, journal={TOXICOLOGICAL SCIENCES}, author={Rider, Cynthia V. and LeBlanc, Gerald A.}, year={2006}, month={Oct}, pages={443–449} }
 @article{rider_leblanc_2005, title={An integrated addition and interaction model for assessing toxicity of chemical mixtures}, volume={87}, ISSN={["1096-0929"]}, DOI={10.1093/toxsci/kfi247}, abstractNote={The high propensity for simultaneous exposure to multiple environmental chemicals necessitates the development and use of models that provide insight into the toxicity of chemical mixtures. In this study, we developed a mathematical model that combines concepts of concentration addition, response addition, and toxicokinetic chemical interaction to assess toxicity of chemical mixtures. A ternary mixture of acetylcholinesterase inhibiting organophosphates (malathion and parathion) and the P450 inhibitor piperonyl butoxide was used to model toxicity. Concentration-response curves were generated for individual chemicals as well as for mixtures of the chemicals using acute toxicity tests with Daphnia magna. The toxicity of binary combinations of malathion and parathion adhered to the principles of concentration addition. The contribution of piperonyl butoxide to mixture toxicity was integrated using a model for response addition. Piperonyl butoxide also modified the toxicity of the organophosphates by inhibiting their metabolic activation. The antagonistic effects of piperonyl butoxide towards the organophosphates were quantified as coefficients of interactions (K-functions) and incorporated into the mixture model. Finally, toxicity of the ternary mixture was modeled at 30 different mixture formulations using three additive models that assumed no interaction (concentration addition, response addition, and integrated addition) and using the integrated addition and interaction (IAI) model. Toxicity of the 30 mixtures was then experimentally determined and compared to model results. Only the IAI model accurately predicted the toxicity of the mixtures. The IAI model holds promise as a means for assessing hazard of complex chemical mixtures.}, number={2}, journal={TOXICOLOGICAL SCIENCES}, author={Rider, CV and LeBlanc, GA}, year={2005}, month={Oct}, pages={520–528} }
 @article{mu_rider_hwang_hoy_leblanc_2005, title={Covert signal disruption: Anti-ecdysteroidal activity of bisphenol a involves cross talk between signaling pathways}, volume={24}, ISSN={["1552-8618"]}, DOI={10.1897/04-063r.1}, abstractNote={Abstract}, number={1}, journal={ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY}, author={Mu, XY and Rider, CV and Hwang, GS and Hoy, H and LeBlanc, GA}, year={2005}, month={Jan}, pages={146–152} }
 @article{rider_gorr_olmstead_wasilak_leblanc_2005, title={Stress signaling: coregulation of hemoglobin and male sex determination through a terpenoid signaling pathway in a crustacean}, volume={208}, ISSN={["1477-9145"]}, DOI={10.1242/jeb.01343}, abstractNote={SUMMARY}, number={1}, journal={JOURNAL OF EXPERIMENTAL BIOLOGY}, author={Rider, CV and Gorr, TA and Olmstead, AW and Wasilak, BA and Leblanc, GA}, year={2005}, month={Jan}, pages={15–23} }
 @article{mu_rider_leblanc_2002, title={Abstracts from the Eleventh International Symposium on Pollutant Responses in Marine Organisms (PRIMO 11) - Endocrine disrupters}, volume={54}, number={3-5}, journal={Marine Environmental Research}, author={Mu, X. Y. and Rider, C. V. and Leblanc, G. A.}, year={2002}, pages={741–754} }