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Project Publications: Texas A&M University: Halogenated Aromatics

Superfund Research Program

Halogenated Aromatics

Project Leader: Stephen H. Safe
Grant Number: P42ES004917
Funding Period: 1995 - 2000
View this project in the NIH Research Portfolio Online Reporting Tools (RePORT)

Project-Specific Links



  • Barhoumi R, Mouneimne Y, Ramos KS, Safe SH, Phillips TD, Centonze VE, Ainley C, Gupta MS, Burghardt RC. 2000. Analysis of Benzo[a]pyrene partitioning and cellular homeostasis in a rat liver cell line. Toxicol Sci 53:264-270. PMID:10696774
  • Gaido KW, Maness SC, McDonnell DP, Dehal SS, Kupfer D, Safe SH. 2000. Interaction of methoxychlor and related compounds with estrogen receptor alpha and beta, and androgen receptor: structure-activity studies. Mol Pharmacol 58(4):852-858. PMID:10999957
  • Kester MH, Bulduk S, Tibboel D, Meinl W, Glatt H, Falany CN, Coughtrie MW, Bergman A, Safe SH, Kuipper GG, Schuur AG, Brouwer A, Visser TJ. 2000. Potent inhibition of estrogen sulfotransferase by hydroxylated PCB metabolites: a novel pathway explaining the estrogenic activity of PCBs. Endocrinology 141(5):1897-1900. doi:10.1210/endo.141.5.7530 PMID:10803601
  • Safe SH. 2000. Endocrine disruptors and human health - is there a problem: an update. Environ Health Perspect 108(6):487-493. PMID:10856020
  • Safe SH. 2000. Toxicology of persistent organic pollutants. European Journal of Lipid Science and Technology 102:52-53.
  • Safe SH. 2000. Xenoestrogens and human health. Is there a problem? The argument against. Progr. Environmental Science 21:21-30.
  • Yoon K, Pallaroni L, Ramamoorthy K, Gaido KW, Safe SH. 2000. Ligand structure-dependent differences in activation of estrogen receptor alpha in human HepG2 liver and U2 osteogenic cancer cell lines. Mol Cell Endocrinol 162(1-2):211-220. PMID:10854714
  • Aggett PJ, Kuiper HA, eds. 2000. Reproductive effects: endocrine disruption. In: Risk Assessment in the Food Chain of Children. Nestle Nutrition Workshop Series, Paediatric Programme, Nestec Ltd. Vevey/Lippincott Williams & Wilkins, Philadelphia, PA.


  • Gaido KW, Leonard LS, Maness SC, Hall JM, McDonnell DP, Saville B, Safe SH. 1999. Differential interaction of the methoxychlor metabolite 2,2-bis-(p-hydroxyphenyl)-1,1,1-trichloroethane with estrogen receptors alpha and beta. Endocrinology 140(12):5746-5753. doi:10.1210/endo.140.12.7191 PMID:10579340
  • Ramamoorthy K, Gupta MS, Sun G, McDougal A, Safe SH. 1999. 3,3',4,4'-Tetrachlorobiphenyl exhibits antiestrogenic and antitumorigenic activity in the rodent uterus and mammary and in human breast cancer cells. Carcinogenesis 20:115-123. PMID:9934858
  • Safe SH. 1999. Development and application of TEFs. Human and Ecological Risk Assessment: An International Journal 5:9-12.
  • Safe SH. 1999. Endocrine disruptors and human health - an update. Organohalogen Compounds 42:15-18.
  • Marquardt H, Schafer SG, Welsch F, eds. 1999. Toxic equivalency factors and their use in hazard and risk assessment. In: Toxicology. Academic Press, San Diego, CA. pp.1191-1197.


  • Ake, Jr., Connor K, Ramamoorthy K, Moore M, Wang F, Mustain M, Chen I, Zacharewski TR, Gillesby B, Joyeux A, Belaguer P, Gaido KW, Leonard LS, Maness SC, McDonnell DP. 1998. Estrogenic activity of hydroxylated polychlorinated biphenyls (PCBs) and their interaction. In: Hormonal Toxicants in Food, Proceedings. John Wiley, pp.200-207.
  • Gaido KW, Dohme L, Wang F, Chen I, Blankvoort B, Ramamoorthy K, Safe SH. 1998. Comparative estrogenic activity of wine extracts and organochlorine pesticide residues in food. Environ Health Perspect 106S:1347-1351. PMID:9860891
  • Gould JC, Leonard LS, Maness SC, Wagner BL, Connor K, Zacharewski TR, Safe SH, McDonnell DP, Gaido KW. 1998. Bisphenol A interacts with the estrogen receptor α in a distinct manner from estradiol. Mol Cell Endocrinol 142:203-214. PMID:9783916
  • Gupta MS, Miggins J, Parrish AR, Womack J, Ramos KS, Rodriguez LV, Goldstein L, Holtzapple C, Stanker LH, Safe SH. 1998. Ah receptor-independent induction of CYP1A2 gene expression in genetically inbred mice. Environ Toxicol Pharmacol 5:205-213. PMID:21781866
  • Gupta MS, Ramamoorthy K, Safe SH. 1998. Antiestrogenic activity of 3,3',4,4'-tetrachlorobiphenyl and 3,3',4,4',5-pentachlorobiphenyl in T47D human breast cancer cells. Organohalogen Compounds 37:297-300.
  • Hoivik D, Safe SH. 1998. Polychlorinated biphenyls. In: Environmental and Occupational Medicine. Lippincott-Raven, Philadelphia, PA. pp.1205-1214.
  • Safe SH. 1998. Development validation and problems with the toxic equivalency factor approach for risk assessment of dioxins and related compounds. J Anim Sci 76:134-141. PMID:9464894
  • Safe SH. 1998. Hazard and risk assessment of chemical mixtures using the toxic equivalency factor approach. Environ Health Perspect 106(supp.4):1051-1058. PMID:9703492
  • Safe SH. 1998. Interactions between hormones and chemicals in breast cancer. Annu Rev Pharmacol Toxicol 38:121-158. PMID:9597151
  • Safe SH, Connor K, Gaido KW. 1998. Methods for xenoestrogen testing. Toxicol Lett 102/103:661-666. PMID:10022332
  • Safe SH, Gaido KW. 1998. Phytoestrogens and anthropogenic estrogenic compounds. Environ Toxicol Chem 17:119-126.
  • Safe SH, Wilson CL. 1998. Health effects and risk assessment of halogenated aromatic hydrocarbons. Cent Eur J Public Health 6:113-116.
  • Wilson CL, Safe SH. 1998. Mechanisms of ligand-induced aryl hydrocarbon receptor-mediated biochemical and toxic responses. Toxicol Pathol 26:657-671. PMID:9789953


  • Connor K, Ramamoorthy K, Moore M, Mustain M, Chen I, Safe SH, Zacharewski TR, Gillesby B, Joyeux A, Belaguer P. 1997. Hydroxylated polychlorinated biphenyls (PCBs) as estrogens and antiestrogens: structure-activity relationships. Toxicol Appl Pharmacol 145:111-123. PMID:9221830
  • Fielden MR, Chen I, Chittim B, Safe SH, Zacharewski TR. 1997. Examination of the estrogenicity of 2,4,6,2',6'-pentachlorobiphenyl (PCB 104), its hydroxylated metabolite 2,4,6,2',6'-pentachloro-4-biphenylol (HO-PCB 104), and a further chlorinated derivative, 2,4,6,2',4',6'-hexachlorobiphenyl (PCB 155). Environ Health Perspect 105(11):1238-1248. PMID:9370515 PMCID:PMC1470342
  • Moore M, Mustain M, Daniel KD, Chen I, Safe SH, Zacharewski TR, Gillesby B, Joyeux A, Belaguer P. 1997. Antiestrogenic activity of hydroxylated polychlorinated biphenyl congeners identified in human serum. Toxicol Appl Pharmacol 142:160-168. PMID:9007045
  • Ramamoorthy K, Vyhlidal C, Wang F, Chen I, Safe SH, McDonnell DP, Leonard LS, Gaido KW. 1997. Additive estrogenic activities of a binary mixture of 2',4',6'-trichloro- and 2',3',4',5'-tetrachloro-4-biphenylol. Toxicol Appl Pharmacol 147:93-100. PMID:9356311
  • Ramamoorthy K, Wang F, Chen I, Norris JD, McDonnell DP, Gaido KW, Bocchinfuso WP, Korach KS, Safe SH. 1997. Potency of combined estrogenic pesticides. Science 275:405. PMID:9005556
  • Ramamoorthy K, Wang F, Chen I, Norris JD, McDonnell DP, Leonard LS, Gaido KW, Bocchinfuso WP, Korach KS, Safe SH. 1997. Estrogenic activity of a dieldrin/toxaphene mixture in the mouse uterus, MCF-7 human breast cancer cells, and yeast-based estrogen receptor assays: no apparent synergism. Endocrinology 138:1520-1527. PMID:9075711
  • Safe SH. 1997. Limitations of the toxic equivalency factor approach for risk assessment of TCDD and related compounds. Teratog Carcinog Mutagen 17:285-304. PMID:9508738
  • Safe SH, Connor K, Ramamoorthy K, Gaido KW, Maness SC. 1997. Human exposure to endocrine-active chemicals: hazard assessment problems. Regul Toxicol Pharmacol 26:52-58. PMID:9339480
  • Wang W, Porter WW, Burghardt RC, Safe SH. 1997. Mechanism of inhibition of MDA-MB-468 cell growth by 2,3,7,8,-tetrachlorodibenzo-p-dioxin. Carcinogenesis 18:925-933. PMID:9163677
  • Wang W, Smith, III R, Burghardt RC, Safe SH. 1997. 17 beta-Estradiol-mediated growth inhibition of MDA-MB-468 cells stably transfected with the estrogen receptor: cell cycle effects. Mol Cell Endocrinol 133(1):49-62. PMID:9359472
  • Willett KL, Safe SH. 1997. Hydroxylated polychlorinated biphenyls identified in human serum as inducers and inhibitors of EROD activity in the H4IIE cell bioassay. Organohalogen Compounds 34:172-177.
  • Zacharewski TR, Sutter TR, Safe SH, Greenlee WF, Connolly RB. 1997. Concerns with the use of a toxic equivalency factor (TEF) approach for risk assessment of "dioxin-like" compounds. Organohalogen Compounds 34:91-94.
  • Zhao F, Mayura K, Kocurek N, Edwards JF, Kubena LF, Safe SH, Phillips TD. 1997. Inhibition of 3,3',4,4',5-pentachlorobiphenyl-induced chicken embryotoxicity by 2,2',4,4',5,5'-hexachlorobiphenyl. Fundam Appl Toxicol 35:1-8. PMID:9024668


  • Barhoumi R, Mouneimne Y, Phillips TD, Safe SH, Burghardt RC. 1996. Alteration of oxytocin-induced calcium oscillations in Clone 9 cells by toxin-exposure. Fundam Appl Toxicol 33:220-228. PMID:8921340
  • Bowes RC, Parrish AR, Steinberg MA, Willett KL, Zhao W, Savas U, Jefcoate CR, Safe SH, Ramos KS. 1996. Atypical cytochrome P450 profiles in glomerular mesangial cells at the mRNA and enzyme level. Evidence for CYP1A1 and CYP1B1 expression and their involvement in benzo(a)pyrene metabolism. Biochem Pharmacol 52(4):587-595. doi:10.1016/0006-2952(96)00310-3 PMID:8759031
  • Hanneman WH, Legare ME, Barhoumi R, Burghardt RC, Safe SH, Tiffany-Castiglioni E. 1996. Stimulation of calcium uptake in cultured rat hippocampal neurons by 2,3,7,8-tetrachlorodibenxo-p-dioxin (TCDD). Toxicology 112:19-28. PMID:8792845
  • Markiewicz KV, Howie LE, Safe SH, Donnelly KC. 1996. Mutagenic potential of binary and complex mixtures using different enzyme induction systems. J Toxicol Environ Health A 47:443-451. PMID:8614014
  • Washburn KS, Huebner HJ, Safe SH, Phillips TD, Donnelly KC. 1996. Development of an Instrumental Fractionation and Quantitation Scheme for Selected Polynuclear Aromatic Hydrocarbons Present in extracts from Wood-Preserving Waste. In: Proceedings of the Hazardous Substance Research Center (HSRC) / Waste-Management Education & Research Consortium Joint Conference on the Environment. pp.400-407.


  • Bowes RC, Ramos KS. 1995. Renal mesangial cell proliferation is enhanced by sequential challenge with benzo(a)pyrene and 2,3,7,8-tetrachlorodibenzo-p-dioxin. Organohalogen Compounds 25:253-258.
  • Chaloupka K, Steinberg MA, Santostefano M, Rodriguez LV, Goldstein L, Safe SH. 1995. Induction of Cyp1a-1 and Cyp1a-2 gene expression by a reconstituted mixture of polynuclear aromatic hydrocarbons in B6C3F1 mice. Chem Biol Interact 96:207-221. PMID:7750161
  • Connor K, Harper N, Safe SH. 1995. Toxic equivalency factors for mono- and diortho-substituted PCB congeners in B6C3F1 mice. Organohalogen Compounds 25:319-322.
  • Connor K, Safe SH. 1995. Development and validation of toxic equivalency factors (TEFs) for PCBs in female Sprague-Dawley rats. Organohalogen Compounds 25:323-326.
  • Connor K, Safe SH, Jefcoate CR, Larsen M. 1995. Structure-dependent induction of CYP2B by polychlorinated biphenyl congeners in female Sprague-Dawley rats. Biochem Pharmacol 50:1913-1920. PMID:8615872
  • Connor K, Steinberg MA, Safe SH, Harper N. 1995. Immunosuppressive activity of polychlorinated biphenyl mixtures and congeners: non-additive (antagonistic) interactions. Fundam Appl Toxicol 27(1):131-139. doi:10.1006/faat.1995.1116 PMID:7589923
  • Dickerson R, Howie-Keller L, Safe SH. 1995. Alkyl polychlorinated dibenzofurans and related compounds as antiestrogens in the female rat uterus: Structure-Activity Studies. Toxicol Appl Pharmacol 135:287-298. PMID:8545839
  • Harper N, Steinberg MA, Thomsen J, Safe SH. 1995. Halogenated aromatic hydrocarbon-induced suppression of the plaque-forming cell response in B6C3F1 splenocytes cultured with allogenic mouse serum: Ah receptor structure activity relationships. Toxicology 99:199-206. PMID:7610466
  • Ou X, Ramos KS. 1995. Regulation of cytochrome P451A1 gene expression in vascular smooth muscle cells through aryl hydrocarbon receptor-mediated signal transduction requires a protein synthesis inhibitor. Arch Biochem Biophys 318:122-130. PMID:7840604
  • Safe SH. 1995. Human dietary intake of aryl hydrocarbon (Ah) receptor agonists: mass balance estimates of exodioxins and endodioxins and implications for health assessment. Organohalogen Compounds 26:7-13.
  • Safe SH, Rodriguez LV, Goldstein L. 1995. Toxic equivalency factor approach for risk assessment of combustion by-products. Toxicol Sci 49:181-191.
  • Safe SH, Washburn KS, Zacharewski TR, Phillips TD. 1995. Synthesis and characterization of hydroxylated polychlorinated biphenyls (PCBs) identified in human serum. Chemosphere 31(4):3017-3023. doi:10.1016/0045-6535(95)00162-2 PMID:7552046
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