Abstract
The inorganic mercurial thiomersal (merthiolate) has been used as an effective preservative in numerous medical and non-medical products since the early 1930s. Both the potential toxicity of thiomersal and sensitisation to thiomersal in relation to the application of thiomersal-containing vaccines and immunoglobulins, especially in children, have been debated in the literature.
The very low thiomersal concentrations in pharmacological and biological products are relatively non-toxic, but probably not in utero and during the first 6 months of life. The developing brain of the fetus is most susceptible to thiomersal and, therefore, women of childbearing age, in particular, should not receive thiomersal-containing products. Definitive data of doses at which developmental effects occur are not available. Moreover, revelation of subtle effects of toxicity needs long term observation of children.
The ethylmercury radical of the thiomersal molecule appears to be the prominent sensitiser. The prevalence of thiomersal hypersensitivity in mostly selected populations varies up to 18%, but higher figures have been reported. The overall exposure to thiomersal differs considerably between countries. In many cases a positive routine patch test to thiomersal should be considered an accidental finding without or, probably more accurately, with low clinical relevance.
In practice, some preventive measures can be taken with respect to thiomersal hypersensitivity. However, with regard to the debate on primary sensitisation during childhood and renewed attention for a reduction of children’s exposure to mercury from all sources, the use of thiomersal should preferably be eliminated or at least be reduced. In 1999 the manufacturers of vaccines and immunoglobulins in the US and Europe were approached with this in mind. The potential toxicity in children seems to be of much more concern to them than the hidden sensitising properties of thiomersal.
In The Netherlands, unlike many other countries, the exposure to thiomersal from pharmaceutical sources has already been reduced. Replacement of thiomersal in all products should have a high priority in all countries.
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References
Veen AJ van’t, Joost Th van. Sensitization to thiomersal (Merthiolate) is still present today. Contact Dermatitis 1994; 31: 293–8
Aberer W, Reiter E, Ziegler V, et al. The importance of including thimerosal, an increasingly frequent allergen in Europe, in standard screening series for allergic contact dermatitis. Am J Contact Dermat 1991; 2: 110–2
Committees on Infectious Diseases and Environmental Health, 1999–2000. Joint statement of the American Academy of Pediatrics (AAP) and United States Public Health Service (USPHS); thimerosal in vaccines: an interim report to clinicians. Pediatrics 1999; 104(3): 568–74
Parfitt K, editor. The extra pharmacopoeia. 31st ed. London: The Pharmaceutical Press, 1996: 1147–8
Axton JHM. Six cases of poisoning after a parenteral organic mercurial compound (Merthiolate). Postgrad Med J 1972; 48: 417–21
Amin-Zaki L, Elhassani S, Majeed MA, et al. Intra-uterine methylmercury poisoning in Iraq. Pediatrics 1974; 54: 587–95
Pfab R, Mückter H, Roider G, et al. Clinical course of severe poisoning with thiomersal. Clin Toxicol 1996; 34(4): 453–60
Lowell JA, Burgess S, Shenoy S, et al. Mercury poisoning associated with hepatitis-B immunoglobulin. Lancet 1996; 347: 480
Amin-Zaki L, Majeed MA, Elhassani S, et al. Prenatal methyl-mercury poisoning: clinical observations over five years. Am J Dis Child 1979; 133: 172–7
Grandjean P, Weihe P, White RF, et al. Cognitive deficit in 7-year-old children with prenatal exposure to methylmercury. Neurotoxicol Teratol 1997; 19: 417–28
Elferink JGR. Thimerosal: a versatile sulfhydryl reagent, calcium mobilizer, and cell function-modulating agent. Gen Pharmacol 1999; 33: 1–6
Rietschel RL, Fowler Jr JF, editors. Fisher’s contact dermatitis. 4th ed. Philadelphia (PA): Lea & Febiger, 1996
Hansson H, Möller H. Patch test reactions to merthiolate in healthy young subjects. Br J Dermatol 1970; 83: 349–56
Hansson H, Möller H. Cutaneous reactions to merthiolate and their relationship to vaccination with tetanus toxoid. Acta Allergol 1971; 26: 150–6
Möller H. Merthiolate allergy: A nationwide iatrogenic sensitization. Acta Derm Venereol 1977; 57: 509–17
Förström L, Hannuksela M, Kousa M, et al. Merthiolate hypersensitivity and vaccination. Contact Dermatitis 1980; 6: 241–5
Cox NH, Forsyth A. Thiomersal allergy and vaccination reactions. Contact Dermatitis 1988; 18: 229–33
Tosti A, Guerra L, Bardassi F. Hyposensitizing therapy with standard antigenic extracts: an important source of thimerosal sensitization. Contact Dermatitis 1989; 20: 173–6
Aberer W. Vaccination despite thimerosal sensitivity. Contact Dermatitis 1991; 24; 6–10
Lisi P, Perno P, Ottaviani M, et al. Minimum eliciting patch test concentration of thimerosal. Contact Dermatitis 1991; 24: 2–6
Seidenari S, Manzini BM, Danese P, et al. Patch and prick test study of 593 healthy subjects. Contact Dermatitis 1990; 23: 162–7
Osawa J, Kitamura K, Ikezawa Z, et al. A probable role for vaccines containing thimerosal in thimerosal hypersensitivity. Contact Dermatitis 1991; 24: 178–82
Wong WK, Tan C, Ng SK, et al. Thimerosal allergy and its relevance in Singapore. Contact Dermatitis 1992; 26: 195–6
Weston WL, Weston JA, Kinoshita J, et al. Prevelance of positive epicutaneous tests among infants, children and adolescents. Pediatrics 1986; 78: 1070–4
Storrs FJ, Rosenthal LE, Adams RM, et al. Prevalence and relevance of allergic reactions in patients patch tested in North America — 1984 to 1985. J Am Acad Dermatol 1989; 20: 1038–45
Barros MA, Batista A, Correia TM, et al. Patch testing in children: a study of 562 schoolchildren. Contact Dermatitis 1991; 25: 156–9
Manzini BM, Ferdani G, Simonetti V, et al. Contact sensitization in children. Pediatric Dermatol 1998; 15: 12–7
Rees S, Gibson J, Forsyth A, et al. Thiomersal sensitivity in health care workers. Br Dent J 1997; 183(11/12): 395
Schnuch A, Uter W, Geier J, et al. Contact allergies in healthcare workers. Results from the IVDK. Acta Derm Venereol 1998; 78: 358–63
Josephson JE, Caffery BE. Hydrogel lens solutions. Int Ophthalmol Clin 1981; 21: 163–71
Zenarola P, Gimma A, Lomuto M. Systemic contact dermatitis from thimerosal. Contact Dermatitis 1995; 32: 107–8
Zemtsov A, Bolton GG. Thimerosal-induced bullous contact dermatitis. Contact Dermatitis 1994; 30: 57
McKenna KE. Eczematous reaction to hepatitis B vaccine. Contact Dermatitis 1999; 40: 158–9
Wilson LA, McNatt J, Reitschel R. Delayed hypersensitivity to thimerosal in soft contact lens wearers. Ophthalmology 1981; 8: 804–9
Wright P, Mackie I. Preservative-related problems in soft contact lens wearers. Trans Ophthalmol Soc U K 1982; 102: 3–6
Zadnik K. Severe allergic reaction to saline preserved with thiomerosal. J Am Optom Assoc 1984; 7: 507–9
Tosti A, Tosti G. Thimerosal: a hidden allergen in ophthalmology. Contact Dermatitis 1988; 18: 268–73
Patrizi A, Rizzoli L, Vincenzi C, et al. Sensitization to thimerosal in atopic children. Contact Dermatitis 1999; 40: 94–7
Fräki JE, Kalimo K, Tuohimaa P, et al. Contact allergy to various components of topical preparations for treatment of external otitis. Acta Otolaryngol 1985; 100: 414–8
Honigman JL. Disinfectant ototoxicity. Pharm J 1975; 215: 523
Luka RE, Oppenheimer JJ, Miller N, et al. Delayed hypersensitivity to thiomersal in Rh (D) immunoglobulin. J Allergy Clin Immunol 1997; 100(1): 138–9
Lindemayr H, Drobil M, Ebner H. Impfreaktione nach Tetanus- und Frühsommermeningoenzephalitis-Schutzimpfungen durch Merthiolat (Thiomersal). Der Hautarzt 1984; 35: 192–6
Tosti A, Melino M, Bardazzi F. Systemic reactions due to thiomersal. Contact Dermatitis 1986; 15: 187–8
Maibach H. Acute laryngeal obstruction presumed secondary to thiomersal (merthiolate) delayed hyperensensitivity. Contact Dermatitis 1975; 1: 221–2
Pirker C, Möslinger T, Wantke T, et al. Ethylmercuric chloride: the responsible agent in thiomersal hypersensitivity. Contact Dermatitis 1993; 29: 152–4
Wantke F, Demmer CM, Götz M, et al. Contact dermatitis from thimerosal: 2 years’ experience with ethylmercuric chloride in patch testing thimerosal-sensitive patients. Contact Dermatitis 1994; 30: 115–7
Gonçalo M, Figueiredo A, Gonçalo S. Hypersensitivity to thimerosal: the sensitizing moiety. Contact Dermatitis 1996; 34: 201–3
Santucci B, Cannistraci C, Camera E, et al. Thimerosal positivities. Contact Dermatitis 1996; 35: 366–7
Santucci B, Cannistraci C, Cristaudo A, et al. Thimerosal positivities: the role of organomercury alkyl compounds. Contact Dermatitis 1998; 38: 325–8
Santucci B, Cannistraci C, Cristaudo A, et al. Thimerosal positivities: the role of SH-groups and divalent ions. Contact Dermatitis 1998; 39: 123–6
McKerrow KJ, Greig DB. Piroxicam-induced photosensitive dermatitis. J Am Acad Dermatol 1986; 15: 1237–41
Serrano G, Bonillo J, Aliaga A, et al. Piroxicam-induced photosensitivity and contact sensitivity to thiosalicylic acid. J Am Acad Dermatol 1990; 23: 479–83
Cirne de Castro JL, Freitas JP, Menezes Brandão T, et al. Sensitivity to thimerosal and photosensitivity to piroxicam. Contact Dermatitis 1991; 24: 187–92
Youn JI, Lee HG, Yeo UC, et al. Piroxicam photosensitivity associated with vesicular hand dermatitis. Clin Exp Dermatol 1993; 18: 52–4
Stingeni L, Lapomarda V, Lisi P. What risk of piroxicam photodermatitis in thimerosal-positive patients? Contact Dermatitis 1996; 34: 60–1
Chishiki M, Kawada A, Fujioka A, et al. Photosensitivity due to ampiroxicam. Dermatology 1997; 195: 409–10
Cox NH, Moss C, Forsyth A. Allergy to non-toxoid constituents of vaccines and implications for patch testing. Contact Dermatitis 1988; 18: 143–6
Jones HT. Danger of skin burns from thiomersal. BMJ 1972; II: 504–5
Cioletti RR. Determination of thimerosal content in contact lens polymers. Int Contact Lens Clin 1980; 13: 3–7
Binder PS, Rasmussen DM, Gordon M. Keratoconjunctivitis and soft lens solutions. Arch Ophthalmol 1981; 99: 87–90
Schilthuis HJ, Wijnen JH van. Thiomersal in gammaglobuline voor zwangere reizigers niet veilig voor de foetus. Ned Tijdschr Geneeskd 1999; 31(1622; 38): 1934–5
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The author thanks Mrs A.M. Geursen-Reitsma, Mrs W.M.B. Lokkerbol and Dr B. Tank for the helpful assistance.
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van ’t Veen, AJ. Vaccines Without Thiomersal. Drugs 61, 565–572 (2001). https://doi.org/10.2165/00003495-200161050-00002
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DOI: https://doi.org/10.2165/00003495-200161050-00002