Selected Studies on the Toxicity of Thimerosal Published in Peer Reviewed Scientific and Medical Journals

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Selected Studies on the Toxicity of Thimerosal Published in Peer Reviewed Scientific and Medical Journals









(With Links to the National Library of Medicine for Complete Abstracts and to Order Copies of Complete Articles with Loansome Doc) TABLE OF CONTENTS A. Toxic Effects of Thimerosal on Vital Mammalian Enzymes B. Chromosomal Aberrations Induced by Thimerosal Exposure C. Disruption of Calcium Homeostasis by Thimerosal D. Allergic Responses to Thimerosal in Vaccines and Opthalmics A. Toxic Effects of Thimerosal on Vital Mammalian Enzymes and Enzyme Systems Rat brain (Na⁺-K⁺)ATPase: modulation of its oubain-sensitive K⁺-PNPPase activity by thimerosal. Lewis and Bowler (1983). Int. J. Biochem. 15:5-7. (6298022) Modified cation activation of the (Na⁺K⁺)-ATPase following treatment with thimerosal. Kaplan and Mone (1985). Arch. Biochem. Biophys. 237:386-395. (2983612) The effects of organic and inorganic mercuric salts on (Na⁺K⁺)ATPase in different cerebral fractions in control and intrauterine growth-retarded rats: alterations induced by serotonin. Chanez et al., (1989). Neurotoxicology 10:699-706. (2562765) Kinetics of merthiolate-induced aggregation of human platelets. Vrzheshch et al., (1992). Thromb. Res. 67:505-516. (1448785) The effects of thimerosal on calcium uptake and inositol 1,4,5-triphosphate-induced calcium release in cerebellar microsomes. Sayers et al., (1993). Biochem. J. 289:883-887. (8435083) Thimerosal interacts with the Ca²⁺ release channel ryanodine receptor from skeletal muscle sarcoplasmic reticulum. Abramson et al., (1995). J. Biol. Chem. 270:29644-29647. (8530347) Effect of thimerosal and other sulfhydryl reagents on calcium permeability in thymus lymphocytes. Pintado et al., (1995). Biochem. Pharmacol. 49:227-232. (7840800) Increased expression of procoagulant activity on the surface of human platelets exposed to heavy metal compounds. Goodwin et al., (1995). Biochem. J. 308:15-21. (7755558) Effects of thimerosal, an organic sulfhydryl modifying agent, on serotonin transport activity into rabbit blood platelets. Nishio et al., (1996). Neurochem. Int. 29:391-394. (8939447) Effects of thimerosal on the transient kinetics of inositol 1,4,5-triphosphate-induced Ca²⁺ release from cerebellar microsomes. Mezna and Michelangeli (1997). Biochem. J. 325:177-182. (9224644) Effects of thiol-modifying agents on a K(Ca²⁺) channel of intermediate conductance in bovine aortic endothelial cells. Cai and Sauve (1997). J. Membr. Biol. 158:147-158. (9230092) Thimerosal: a versatile sulfhydryl reagent, calcium mobilizer, and cell function-modulating agent. Elferink (1999). Gen. Pharmacol. 33:1-6. (10428009) Cardiac ryanodine receptor activity is altered by oxidizing reagents in either the luminal or cytoplasmic solution. Eager and Dulhunty (1999). J. Membr. Biol. 167:205-214. (9929372) Modulation of type 1, 2 and 3 inositol 1,4,5-triphosphate receptors by cyclic ADP-ribose and thimerosal. Vanlingen et al., (1999). Cell Calcium 25:107-114. (10326677) Thimerosal enhances agonist-specific differences between [Ca²⁺]_i oscillations induced by phenylephrine and ATP in single rat hepatocytes. Green et al., (1999). Cell Calcium 25:173-178. (10326684) B. Chromosomal Aberrations Induced by Thimerosal Exposure Analysis of nine known or suspected spindle poisons for mitotic chromosome malsegregation using Saccharomyces cerevisiae D61.M. Albertini S (1990). Mutagenesis 6:65-70. (2263203) Effects of 10 known or suspected spindle poisons in the in vitro porcine brain tubulin assembly assay. Brunner et al., (1991). Mutagenesis 6:65-70. (2038274) In vitro studies with nine known or suspected spindle poisons: results in tests for chromosome malsegregation in Aspergillus nidulans.Crebelli et al., (1991). Mutagenesis 6:131-136. (2056914)
	The detection and assessment of the aneugenic potential of environmental chemicals: the European Community Aneuploidy Project. Parry and Sors. (1993).Mutat Res 287:3-15. (7683383)
	Effects of potential anueploidy inducing agents on microtubule assembly in vitro. Wallin and Hartley-Asp (1993). Mutat. Res. 287:17-22. (7683380)
	An evaluation of the use of in vitro tubulin polymerization, fungal and wheat assays to detect the activity of potential chemical aneugens. Parry (1993). Mutat. Res. 287:23-28. (7683381)
	A comparison of two in vitro mammalian cell cytogenetic assays for the detection of mitotic aneuploidy using 10 known or suspected aneugens. Warr et al., (1993). Mutat. Res. 287:29-46. (7683382)
	Induction of mitotic aneuploidy using Chinese hamster primary embryonic cells. Test results of 10 chemicals. Natarajan et al., (1993). Mutat. Res. 287:47-56. (7683384)
	C-mitosis and numerical chromosome aberration analyses in human lymphocytes: 10 known or suspected spindle poisons. Sbrana et al., (1993). Mutat. Res. 287:57-70. (7683385)
	The cytochalasin-B micronucleus/kinetochore assay in vitro.: studies with 10 suspected aneugens. Lynch and Parry (1993). Mutat. Res. 287:71-86. (7683386)
	An overview of the results of testing of known or suspected aneugens using mammalian cells in vivo. Natarajan (1993).Mutat. Res. 287:113-118. (7683377)
	In vivo studies on chemically induced anueploidy in mouse somatic and germinal cells. Leopardi et al., (1993). Mutat. Res. 287:119-130. (7683378)
	Synopsis of the in vivo results obtained with the 10 known or suspected aneugens tested in the CEC collaborative study. Adler (1993). Mutat. Res. 287:131-137. (7683379)
	Micronucleus test and metaphase analyses in mice exposed to known and suspected spindle poisons. Marrazzini et al., (1994). Mutagenesis 9:505-515. (7854141)

C. Disruption of Calcium Homeostasis by Thimerosal

Modulation of inositol 1,4,5-trisphosphate binding to the various inositol 1,4,5-trisphosphate receptor isoforms by thimerosal and cyclic ADP-ribose. Vanlingen et al., (2001) Biochemical Pharmacology 61:803-809. (11274965)

Thimerosal: a versatile sulfhydryl reagent, calcium mobilizer, and cell function-modulating agent. Elferink JG (1999). Gen Pharmacol 33:1-6. (10428009)

Thimerosal enhances agonist-specific differences between [Ca²⁺]i oscillations induced by phenylephrine and ATP in single rat hepatocytes. Green AK, Cobbold PH, Dixon CJ (1999). Cell Calcium 25:173-8. (10326684)

Modulation of type 1, 2 and 3 inositol 1,4,5-trisphosphate receptors by cyclic ADP-ribose and thimerosal. Vanlingen S, Sipma H, Missiaen L, De Smedt H, De Smet P, Casteels R, Parys JB (1999). Cell Calcium 25:107-14. (10326677)

Effects of thimerosal on the transient kinetics of inositol 1,4,5-trisphosphate-induced Ca²⁺ release from cerebellar microsomes. Mezna M, Michelangeli F (1997). Biochem J 325:177-82. (9224644)

Effects of thimerosal, an organic sulfhydryl modifying agent, on serotonin transport activity into rabbit blood platelets. Nishio H, Nezasa K, Hirano J, Nakata Y (1996). Neurochem Int 29:391-6. (8939447)

Thimerosal-induced Ca²⁺ mobilization in isolated guinea pig cochlear outer hair cells. Chen L, Harada N, Yamashita T (1998). Acta Otolaryngol Suppl 539:28-33. (10095857)

D. Allergic Responses to Thimerosal in Vaccines and Opthalmics

Thiomersal allergy and vaccination reactions. Cox and Forsyth (1988). Contact Dermatitis 18:229-233. (3378430)

Multicenter survey related to the frequency of positive patch tests with mercury and thiomersal. Lachapelle et al., (1988). Ann. Dermatol. Venereol. 115:793-796. (2974266)

Thimerosal: a hidden allergen in opthalmology. Tosti and Tosti (1988). Contact Dermatitis 18:268-273. (3416589)

Toxic effects of opthalmic preservatives on cultured rabbit corneal epithelium. Simmons et al., (1988). Am. J. Optom. Physiol. Opt. 65:867-873. (3252733)

Cytotoxicity and mutagenicity of opthalmic solution preservatives and UVA radiation in L5178Y cells. Withrow et al., (1989). Photochem. Photobiol. 50:385-389. (2780830)

Reactions to thimerosal in hepatitis B vaccines. Rietschel and Adams (1990). Dermatol. Clin. 8:161-164. (2137393)

Patch and prick test study of 593 healthy subjects. Seidenari et al., (1990). Contact Dermatitis 23:162-167. (2282794)

A probable role for vaccines containing thimerosal in thimerosal hypersensitivity. Osawa et al., (1991). Contact Dermatitis 24:178-182. (1868700)

Cytotoxicity of opthalmic preservatives on human corneal epithelium. Tripathi et al., (1992). Lens Eye Toxic Res. 9:361-375. (1301792)

Ethylmercuric chloride: the responsible agent in thimerosal hypersensitivity. Pirker et al., (1993). Contact Dermatitis 29:152-154. (8222628)

Thimerosal induces toxic reaction in non-sensitized animals. Uchida et al., (1994). Int. Arch. Allergy Immunol. 104:296-301. (7518269)

Frequency of sensitization to 13 common preservatives in Switzerland. Swiss Contact Dermititis Research Group. Perrenoud et al., (1994). Contact Dermatitis 30:276-279. (8088140)

Sensitization to thimerosal (Merthiolate) is still present today. van 't Veen and van Joost (1994). Contact Dermatitis 31:293-298. (7867326)

Sensitization to thimerosal and previous vaccination. Schafer et al., (1995). Contact Dermatitis 32:114-116. (7758313)

	Phosphatidylserine synthesis in glioma C6 cells is inhibited by Ca²⁺ depletion from the endoplasmic reticulum: effects of 2,5-di-tert-butylhydroquinone and thimerosal. Wiktorek M, Sabala P, Czarny M, Baranska J (1996). Biochem Biophys Res Commun 224:645-50. (8713102)
	Thimerosal interacts with the Ca²⁺ release channel ryanodine receptor from skeletal muscle sarcoplasmic reticulum. Abramson JJ, Zable AC, Favero TG, Salama G (1995). J Biol Chem 270:29644-7. (8530347)
	Thimerosal increases the responsiveness of the calcium receptor in human parathyroid and rMTC6-23 cells. Mihai R, Lai T, Schofield G, Farndon JR (1999). Cell Calcium 26:95-101. (10598273)
	Effect of thimerosal and other sulfhydryl reagents on calcium permeability in thymus lymphocytes. Pintado E, Baquero-Leonis D, Conde M, Sobrino F (1995). Biochem Pharmacol 49:227-32. (7840800)
	Effect of thimerosal on cytosolic calcium and phosphatidylserine synthesis in Jurkat T cells. Pelassy C, Breittmayer JP, Ticchioni M, Aussel C (1994). Int J Biochem 26:93-6. (8138053)
	Reversible blockade of the calcium-activated nonselective cation channel in brown fat cells by the sulfhydryl reagents mercury and thimerosal. Koivisto A, Siemen D, Nedergaard J (1993). Pflugers Arch 425:549-51. (7510880)
	Thimerosal induced changes of intracellular calcium in human endothelial cells. Gericke M, Droogmans G, Nilius B (1993). Cell Calcium 14:201-7. (8500136)
	The effects of thimerosal on calcium uptake and inositol 1,4,5-trisphosphate-induced calcium release in cerebellar microsomes. Sayers LG, Brown GR, Michell RH, Michelangeli F (1993). Biochem J 289:883-7 (8435083)
	The effects of thimerosal and cyclopiazonic acid on the Ca(²⁺)-pumps from rat cerebellum microsomes. Michelangeli F, DaSilva A, Sayers L, Brown G (1992). Biochem Soc Trans 20:205S. (1327911)
	The thiol reagent, thimerosal, evokes Ca²⁺ spikes in HeLa cells by sensitizing the inositol 1,4,5-trisphosphate receptor. Bootman MD, Taylor CW, Berridge MJ (1992). J Biol Chem 267:25113-9. (1334081)
	Cytosolic Ca²⁺ spikes evoked by the thiol reagent thimerosal in both intact and internally perfused single pancreatic acinar cells. Thorn P, Brady P, Llopis J, Gallacher DV, Petersen OH (1992). Pflugers Arch 422:173-8. (1336850)
	Effect of the sulfhydryl reagent thimerosal on cytosolic free Ca²⁺ and membrane potential of thymocytes. Gukovskaya AS, Trepakova ES, Zinchenko VP, Korystov YN, Bezuglov VV (1992). Biochim Biophys Acta 1111:65-74. (1390866)
	Thimerosal blocks stimulated but not basal release of endothelium-derived relaxing factor (EDRF) in dog isolated coronary artery. Crack P, Cocks T (1992). Br J Pharmacol 107:566-72. (1384915)
	Thimerosal induces calcium mobilization, fructose 2,6-bisphosphate synthesis and cytoplasmic alkalinization in rat thymus lymphocytes. Martin F, Gualberto A, Sobrino F, Pintado E (1991). Biochim Biophys Acta 1091:110-4. (1995061)
	Involvement of calcium in the thimerosal-stimulated formation of leukotriene by fMLP in human polymorphonuclear leukocytes. Hatzelmann A, Haurand M, Ullrich V (1990). Biochem Pharmacol 39:559-67. (2154987)
	The effect of thimerosal on neutrophil migration: a comparison with the effect on calcium mobilization and CD11b expression. Elferink JG, de Koster BM (1998). Biochem Pharmacol 55:305-12. (9484796)
	Enhancement of eicosanoid synthesis in mouse peritoneal macrophages by the organic mercury compound thimerosal. Kaever V, Goppelt-Strube M, Resch K (1988). Prostaglandins 35:885-902. (3141973)
	The sulfhydryl reagent thimerosal elicits human platelet aggregation by mobilization of intracellular calcium and secondary prostaglandin endoperoxide formation. Hecker M, Brune B, Decker K, Ullrich V (1989). Biochem Biophys Res Commun 159:961-8 (2495003)
	Platelet aggregation by thimerosal: role of ADP and SH groups. Leone G, Boni P, Vincenti A (1976). Thromb Haemost 35:249-57. (989191)
	Increased expression of procoagulant activity on the surface of human platelets exposed to heavy-metal compounds. Goodwin CA, Wheeler-Jones CP, Namiranian S, Bokkala S, Kakkar VV, Authi KS, Scully MF (1995) Biochem J 308:15-21. (7755558)
	Thimerosal modulates the agonist-specific cytosolic Ca²⁺ oscillatory patterns in single pancreatic acinar cells of mouse. Wu J, Takeo T, Kamimura N, Wada J, Suga S, Hoshina Y, Wakui M (1996). FEBS Lett 390:149-52. (8706847)
	The effects of thimerosal on the purified InsP3 receptor. Mezna M, Longland CL, Michelangeli F (1998). Biochem Soc Trans 26:S290. (9766009)
	Fertilisation and thimerosal stimulate similar calcium spiking patterns in mouse oocytes but by separate mechanisms. Cheek et al., (1993). Development 119:179-189. (8275854)
	The thiol reagent, thimerosal induces intracellular calcium oscillations in mature human oocytes. Herbert M, Murdoch AP, Gillespie JI (1995). Hum Reprod 10:2183-6. (8567870)
	Sperm, inositol trisphosphate, and thimerosal-induced intracellular Ca²⁺ elevations in rabbit eggs. Fissore RA, Robl JM (1993). Dev Biol 159:122-30. (8365556)
	The effects of thimerosal, a sulfhydryl reagent, on phasic myometrial contractions. Phillippe M (1995). Biochem Biophys Res Commun 211:1-6. (7539999)
	Effects of protein kinase C activation and inhibition on sperm-, thimerosal-, and ryanodine-induced calcium responses of human oocytes. Sousa M, Barros A, Mendoza C, Tesarik J (1996). Mol Hum Reprod 2:699-708. (9239685)

	Complete activation of porcine oocytes induced by the sulfhydryl reagent, thimerosal. Machaty Z, Wang WH, Day BN, Prather RS (1997). Biol Reprod 57:1123-7. (9369179)
	Calcium release and subsequent development induced by modification of sulfhydryl groups in porcine oocytes. Machaty Z, Wang WH, Day BN, Prather RS (1999). Biol Reprod 60:1384-91. (10330097)
	Time course of cortical and zona reactions of pig oocytes upon intracellular calcium increase induced by thimerosal. Wang WH, Machaty Z, Abeydeera LR, Prather RS, Day BN (1999). Zygote 7:79-86. (10216920)
	Intracellular calcium responses in bovine oocytes induced by spermatozoa and by reagents. Nakada K, Mizuno J (1998). Theriogenology 50:269-82. (10734495)