1642 Disinfectants and Preservatives Preparations Profile Almyrol; Baccalin†; Bacillocid rasant†; Desoform†; Freka-Nol; Fugisept†; Gercid forte†; Gigasept Med†; Hexaquart L†; Hexaquart plus; Hexaquart Proprietary Preparations (details are given in Part 3) Dichlorobenzyl alcohol is an antiseptic used chiefly as an ingre- dient of lozenges in the treatment of minor infections of the S; Inova†; Kohrsolin FF; Korsolex Extra; Korsolex FF; Korsolex Plus; Lysofor- Multi-ingredient: Austria: Dermowund. min 3000; Lysoformin spezial; Meliseptol Rapid; Melsept SF; Melsitt; Quato- mouth and throat. hex; Teta Extra; Ital.: Melsept SF; Switz.: Desamon; Thai.: Deconex Preparations 53IN†; USA: Vi Rid-Ready. Dibrompropamidine Isetionate (BANM, rINNM) Proprietary Preparations (details are given in Part 3) Ital.: Neo Borocillina Collutorio; Neo Borocillina Spray. Dibromipropamidiinidi-isetionaatti; Dibromopropamidine Ise- Multi-ingredient: Austral.: Ayrton’s Antiseptic; Logicin Rapid Relief; 1,6-Dihydroxy-2,5-dioxahexane thionate; Dibromopropamidyny diizetionian; Dibrompropa- Sore Throat Chewing Gum†; Strepsils; Strepsils Plus; Austria: Coldangin; midindiisetionat; Dibrompropamidin-diisetionát; Dibrompropa- Neo-Angin; Sulgan 99; Belg.: Neofenox; Strepsils; Strepsils + Lidocaine; Ethylene Glycol Bis(semiformal); (Ethylenedioxy)dimethanol. midine Diisetionate; Dibrompropamidine, diisétionate de; Di- Strepsils Menthol; Strepsils Vit C; Canad.: Strepsils; Strepsils Cherry†; [1,2-Ethanediylbis(oxy)]bismethanol. Chile: Cornina†; Hansaplast Antimicotico; Cz.: Neo-Angin; Strepsils; brompropamidine, Isétionate de; Dibrompropamidini diisetio- Strepsils Menthol a Eucalyptus; Strepsils Plus; Strepsils Vitamin C; Denm.: C4H10O4 = 122.1. nas; Dibrompropamidini Isetionas; Isetionato de dibrompropa- Strepsils; Fin.: Bafucin; Strepsils; Strepsils Menthol; Fr.: Strepsils; Strepsils CAS — 3586-55-8. midina. 3,3′-Dibromo-4,4′-trimethylenedioxydibenzamidine bis(2- Lidocaine; Strepsils Miel-Citron; Strepsils Vitamine C; Strepsilspray Lido- caine; Ger.: Dobendan Synergie; Neo-Angin; Gr.: Strepsils; Hong Kong: hydroxyethanesulphonate). Logicin Rapid Relief; Strepsils; Strepsils Dual Action; Hung.: Neo-Angin; Дибромпропамидина Изетионат Strepsils; Strepsils Menthol and Eucalyptus; Strepsils Plus; Strepsils Vitamin C; India: Cofsils†; Irl.: Strepsils; Strepsils +Plus Anaesthetic; Strepsils Dual O OH C17H18Br2N4O2,2C2H6O4S = 722.4. Action; Strepsils Vitamin C; Israel: Strepsils; Strepsils Plus; Strepsils with HO O CAS — 496-00-4 (dibrompropamidine); 614-87-9 (di- Menthol and Eucalyptus; Strepsils with Vitamin C; Ital.: Arscolloid; Benagol; brompropamidine isetionate). Benagol Mentolo-Eucaliptolo; Benagol Vitamina C; Bio-Arscolloid; Corti- ATC — D08AC01; S01AX14. Arscolloid; Farmagola†; Neo Borocillina; Neo Borocillina Balsamica; Neo Profile 1,6-Dihydroxy-2,5,-dioxahexane is an aldehyde that slowly re- ATC Vet — QD08AC01; QS01AX14. Borocillina C; Neo Borocillina Tosse Compresse; Malaysia: Chericof; Strepsils; Strepsils Dual Action; Neth.: Strepsils; Strepsils Menthol en Euca- leases formaldehyde. It is used for the disinfection of surfaces lyptus; Strepsils Sinaasappel en Vitamine C; NZ: Strepsils; Strepsils Plus An- and of medical and surgical instruments. aesthetic; Strepsils with Vitamin C; Philipp.: Strepsils; Pol.: Neo-Angin; O O Strepsils; Port.: Benoral; Dropcina; Rus.: Astrasept (Астрасепт); Coldact Preparations Lorpils (Колдакт Лорпилс)†; Rinza Lorsept (Ринза Лорсепт); Strepsils (Стрепсилс); Strepsils Plus (Стрепсилс Плюс); Suprima-Lor (Суприма- Proprietary Preparations (details are given in Part 3) H2N NH2 Лор); S.Afr.: Strepsils; Strepsils Eucalyptus Menthol; Strepsils Orange-C; Br Br Strepsils Plus; Strepsils Soothing Honey & Lemon; Singapore: Strepsils; Multi-ingredient: Ger.: Bacillol; Kohrsolin; Korsolex basic; Korsolex Ex- Strepsils Dual Action; Spain: Strepsils; Strepsils con Vitamina C; Strepsils tra. NH NH Lidocaina; Swed.: Bafucin; Strepsils; Switz.: Anginazol; Hextriletten; Lida- zon; Neo-Angin au miel et citron; Neo-Angin avec vitamin C sans sucre; (dibrompropamidine) Neo-Angin sans sucre; Sulgan N; Thai.: Strepsils Butter Menthol Capsicum; Strepsils Plus Anaesthetic; Strepsils Plus Vit C; Strepsils Sugar Free; Throatsil; Turk.: Strepsils; Strepsils C; Strepsils Mentollu; UK: Strepsils; Strepsils with Dioctyldimethylammonium Chloride Pharmacopoeias. In Eur. (see p.vii). Vitamin C. Ph. Eur. 6.2 (Dibrompropamidine Diisetionate). A white or al- Dimethyldioctylammonium Chloride; Dioctyl Dimethyl Ammo- most white, crystalline powder. Freely soluble or soluble in wa- nium Chloride. N,N-Dimethyl-N-octyl-1-octanaminium chloride. ter; slightly soluble in alcohol; practically insoluble in dichlo- Диоктилдиметиламмония Хлорид romethane. A 5% solution in water has a pH of 5.0 to 6.0. Dichloroxylenol (BAN, rINN) C18H40ClN = 306.0. Profile DCMX; Dichlorometaxylenol; Dichloroxylénol; Dichloroxyleno- CAS — 5538-94-3. Dibrompropamidine isetionate is an aromatic diamidine antisep- lum; Dicloroxilenol. 2,4-Dichloro-3,5-xylenol; 2,4-Dichloro-3,5- tic similar to propamidine (p.1660). It is bactericidal against dimethylphenol. Gram-positive bacteria but is less active against Gram-negative Дихлороксиленол H C bacteria and spore-forming organisms. It also has antifungal 3 C8H8Cl2O = 191.1. properties. It is available as topical preparations for the local CAS — 133-53-9. treatment of minor eye and skin infections. Cl Preparations Proprietary Preparations (details are given in Part 3) H3C OH Austral.: Brolene; Brulidine; Irl.: Brolene; Norw.: Brulidine; NZ: Brolene; CH3 UK: Brolene; Brulidine; Golden Eye Ointment; Pickles Antiseptic Cream. N Multi-ingredient: UK: Healthy Feet; No-Sor Nose Balm; RBC; Swarm. Cl Cl CH3 CH3 Dichlordimethylhydantoin Profile Diclorodimetilhidantoína. 1,3-Dichloro-5,5-dimethylhydantoin; CH3 1,3-Dichloro-5,5-dimethylimidazolidine-2,4-dione. Dichloroxylenol is a chlorinated phenolic antiseptic. C5H6Cl2N2O2 = 197.0. Preparations CAS — 118-52-5. Profile Proprietary Preparations (details are given in Part 3) Dioctyldimethylammonium chloride is a quaternary ammonium Multi-ingredient: India: Fairgenol†; UAE: Radol. disinfectant used in preparations for disinfection of surfaces. Cl Preparations N Proprietary Preparations (details are given in Part 3) O O Didecyldimethylammonium Chloride Didecildimetilamonio, cloruro de; Didecyldimonium Chloride. Multi-ingredient: USA: Vi Rid-Ready. N N-Decyl-N,N-demethyl-l-decanaminium chloride. H3C Cl C22H48ClN = 362.1. H3C CAS — 7173-51-5. Dodeclonium Bromide (rINN) ATC — D08AJ06. Profile ATC Vet — QD08AJ06. Bromuro de dodeclonio; Dodeclonii Bromidum; Dodéclonium, Dichlordimethylhydantoin is a disinfectant used as a source of Bromure de; GR-412. [2-(p-Chlorophenoxy)ethyl]dodecyld- chlorine, for sterilising food and dairy equipment and as a bleach. imethylammonium bromide. It contains about 72% w/w of ‘available chlorine’ (see p.1638). HC Додеклония Бромид Bromochlorodimethylhydantoin (C5H6N2O2BrCl = 241.5) is a closely related bromine-releasing compound used for the disin- Cl C22H39BrClNO = 448.9. fection of swimming-pool water. CAS — 15687-13-5. CH

N Cl Dichlorobenzyl Alcohol CH - Alcohol diclorobencílico; 2,4-Dichlorbenzyl-alcoholum; Dichlo- Br CH3 rophenylcarbinol; 2,4-Diklooribentsyyli-alkoholi; 2,4-Diklorben- + H3C N sylalkohol; Diklorobenzil Alkol. 2,4-Dichlorobenzyl alcohol. CH O C7H6Cl2O = 177.0. H3C CAS — 1777-82-8. ATC — R02AA03. Profile ATC Vet — QR02AA03. Didecyldimethylammonium chloride is a quaternary ammonium Profile disinfectant used in preparations for disinfection of the skin and Dodeclonium bromide is an antiseptic that has been included in mucous membranes. It is also used to disinfect instruments and multi-ingredient preparations intended for the treatment of skin Cl surfaces. and anorectal disorders. Preparations Preparations Cl Proprietary Preparations (details are given in Part 3) Proprietary Preparations (details are given in Part 3) Ger.: Amosept; Fungisept; Ital.: Alfa; Farmasept; Thai.: Deconex 50FF†. Multi-ingredient: Belg.: Biogaze; Fr.: Sedorrhoide. HO Multi-ingredient: Fr.: Aniospray 29; Aniospray 41; Aniosyme; Bacterian- os D†; Chlorispray†; Hexanios G+R; Oxitou; Sanytol†; Surfanios; Ger.: Dibrompropamidine Isetionate/Ethylene Oxide 1643

Domiphen Bromide (BAN, USAN, rINN) burns, blistering, irritation, and dermatitis; percutane- peripheral and CNS dysfunction and one patient had signs of Bromuro de domifeno; Domifeenibromidi; Domifenbromid; ous absorption may lead to systemic effects. axonal injury. 1. Jay WM, et al. Possible relationship of ethylene oxide exposure Domiphène, Bromure de; Domipheni Bromidum; NSC-39415; Many materials including plastics and rubber adsorb to cataract formation. Am J Ophthalmol 1982; 93: 727–32. PDDB; Phenododecinium Bromide. Dodecyldimethyl-2-phe- ethylene oxide. If such materials are being sterilised 2. Brashear A, et al. Ethylene oxide neurotoxicity: a cluster of 12 noxyethylammonium bromide. nurses with peripheral and central nervous system toxicity. Neu- with ethylene oxide all traces of the gas must be re- rology 1996; 46: 992–8. Домифена Бромид moved before the materials can be used; removal may C22H40BrNO = 414.5. Hypersensitivity. Anaphylactoid reactions in dialysis patients CAS — 13900-14-6 (domiphen); 538-71-6 (domiphen be by ventilation or more active means. Hypersensitiv- have resulted from the use of dialysis equipment sterilised with bromide). ity reactions, including anaphylaxis, have been associ- ethylene oxide.1-3 There have also been reports of ATC — A01AB06. ated with ethylene oxide-contaminated materials. hypersensitivity4 and anaphylactoid5 reactions in plateletpher- ATC Vet — QA01AB06. Ethylene oxide may also react with materials being esis donors caused by residues of ethylene oxide in components of apheresis kits. The most common adverse reactions reported sterilised to produce substances such as ethylene have been dyspnoea, wheezing, urticaria, flushing, headache, chlorohydrin (with chloride) or ethylene glycol (with and hypotension, but acute severe bronchospasm, circulatory H3C water); these may contribute to any toxicity. collapse, cardiac arrest, and death have also occurred. It was (CH ) CH 6 O + 2 11 3 − Pharmaceutical manufacturers within the EU have noted that where severe, sometimes fatal, anaphylactoid reac- N Br tions have occurred at the beginning of dialysis, ethylene oxide been advised to use ethylene oxide only when there is has almost universally been implicated, although exposure to cu- CH3 no alternative. Ethylene oxide has been shown to have prammonium cellulose (cuprophane) dialysis membranes may carcinogenic and mutagenic properties and there is also have been involved. It has been reported that there may be an increased risk of ethyl- Pharmacopoeias. In Br. Chin. includes the monohydrate. evidence of increased risk of neoplasms following oc- ene oxide-induced anaphylactic shock in children undergoing . Colourless or faintly yellow, cupational exposure. BP 2008 (Domiphen Bromide) surgery for spina bifida.7 Such children might be at increased risk crystalline flakes. Freely soluble in water and in alcohol; soluble ◊ Reviews. of sensitisation and anaphylaxis, and came into frequent contact in acetone. 1. WHO. Ethylene oxide. Environmental Health Criteria 55. Gene- with ethylene oxide through multiple operations and catheterisa- Incompatibility. Domiphen bromide is incompatible with va: WHO, 1985. Available at: http://www.inchem.org/ tions. soaps and other anionic surfactants. documents/ehc/ehc/ehc55.htm (accessed 15/03/06) Occupational asthma and contact dermatitis have been attributed 2. WHO. Ethylene oxide health and safety guide. IPCS Health and 8 Profile Safety Guide 16. Geneva: WHO, 1988. Available at: http:// to residual ethylene oxide in surgical gloves. Domiphen bromide is a quaternary ammonium antiseptic with www.inchem.org/documents/hsg/hsg/hsg016.htm (accessed 1. Bommer J, et al. Anaphylactoid reactions in dialysis patients: actions and uses similar to those of other cationic surfactants (see 15/03/06) role of ethylene-oxide. Lancet 1985; ii: 1382–5. 3. WHO. Ethylene oxide. Concise International Chemical Assess- 2. Rumpf KW, et al. Association of ethylene-oxide-induced IgE an- Cetrimide, p.1634). Preparations containing domiphen bromide tibodies with symptoms in dialysis patients. Lancet 1985; ii: are used in the treatment of minor infections of the mouth and ment Document 54 Geneva: WHO, 2003. Available at: http:// www.who.int/ipcs/publications/cicad/en/cicad54.pdf (accessed 1385–7. throat. 15/03/06) 3. Röckel A, et al. Ethylene oxide hypersensitivity in dialysis pa- Preparations tients. Lancet 1986; i: 382–3. Carcinogenicity. Exposure of workers to ethylene oxide has 4. Leitman SF, et al. Allergic reactions in healthy plateletpheresis Proprietary Preparations (details are given in Part 3) been associated with the development of lymphatic and haemato- donors caused by sensitization to ethylene oxide gas. N Engl J Canad.: Antiseptique Pastilles; Bronchodex Pastilles; Ital.: Bradoral; Ma- poietic cancer and there is concern that it may be linked to breast Med 1986; 315: 1192–6. laysia: Domidin; Port.: Neobradoral. cancer. In order to evaluate the carcinogenicity of ethylene oxide 5. Muylle L, et al. Anaphylactoid reaction in platelet-pheresis do- Multi-ingredient: Austria: Bepanthen; Bradosol; Canad.: Nupercainal; the National Institute for Occupational Safety and Health (NI- nor with IgE antibodies to ethylene oxide. Lancet 1986; ii: 1225. Chile: Oralfresh Menta; Fr.: Fluoselgine; Ital.: Inalar; Pol.: Viosept. OSH), in the mid 1980s, assembled a cohort of about 18 000 6. Nicholls A. Ethylene oxide and anaphylaxis during haemodialy- 1-3 sis. BMJ 1986; 292: 1221–2. workers exposed to ethylene oxide. Results of the initial cohort 7. Moneret-Vautrin DA, et al. High risk of anaphylactic shock dur- followed up to 1987 showed no overall excess of haematopoietic ing surgery for spina bifida. Lancet 1990; 335: 865–6. Ethoxyquin cancer, but did find a significant excess of non-Hodgkin’s lym- 8. Verraes S, Michel O. Occupational asthma induced by ethylene 1 Etoxiquina. 6-Ethoxy-1,2-dihydro-2,2,4-trimethylquinoline. phoma among men. Based on limited clinical evidence from hu- oxide. Lancet 1995; 346: 1434–5. mans and from significant evidence in animal studies, the Inter- 1 C14H19NO = 217.3. Pregnancy. A study of female staff responsible for sterilising CAS — 91-53-2. national Agency for Research on Cancer concluded in 1994 that instruments was carried out in all general hospitals in Finland. there was sufficient evidence to classify ethylene oxide as a def- 4 3 The incidence of spontaneous abortion (analysed according to inite human carcinogen. A later evaluation of the NIOSH co- employment at the time of conception and corrected for maternal hort from 1987 to 1998 indicated that, despite 2852 deaths as age, parity, decade of pregnancy, smoking, and consumption of H CH3 N opposed to 1177 deaths in the earlier study, there was little evi- alcohol and coffee) was significantly increased in those exposed dence of cancer excesses for ethylene oxide exposed workers to ethylene oxide during pregnancy compared with those not so CH3 versus the general population, with the exception of bone cancer exposed. This study provoked criticism,2,3 and the authors con- (6 deaths), and no conclusion could be drawn from this small ceded that the study was not large enough to compare abortion 3C OH number. However, exposure-response analyses found statistical- rates and known ethylene oxide concentrations.4 A retrospective ly significant evidence of an association between increased ex- analysis5 of 32 dental assistants who had been exposed to ethyl- CH3 posure and some types of haematopoietic cancer (non-Hodgkin’s ene oxide during pregnancy suggested that, after adjusting for lymphoma and lymphocytic leukaemia), particularly for 2,3 age, the risk of spontaneous abortions and preterm or post-term Profile males. There was also some evidence for a positive exposure- births may have been more than doubled. Ethoxyquin has been used as an antoxidant for the prevention of response for breast cancer. Follow-up of a cohort of 2876 work- 5 1. Hemminki K, et al. Spontaneous abortions in hospital staff en- common scald of apples and pears during storage and as an ad- ers exposed to ethylene oxide in the UK found no statistically gaged in sterilising instruments with chemical agents. BMJ ditive to animal feeds. Concern has been expressed over the tox- significant increase in mortality from cancer overall, or from any 1982; 285: 1461–3. icity of ethoxyquin and its residues on foodstuffs and its use is specific category of tumour. A study6 of a cohort of 7576 female 2. Gordon JE, Meinhardt TJ. Spontaneous abortions in hospital limited or restricted in some countries. workers exposed to ethylene oxide suggested that ethylene oxide sterilising staff. BMJ 1983; 286: 1976. was associated with breast cancer. However, the authors indicat- 3. Austin SG. Spontaneous abortions in hospital sterilising staff. ed weaknesses in the study that could have influenced the find- BMJ 1983; 286: 1976. 4. Hemminki K, et al. Spontaneous abortions in hospital sterilising ings. staff. BMJ 1983; 286: 1976–7. Ethylene Oxide 1. Steenland K, et al. Mortality among workers exposed to ethylene 5. Rowland AS, et al. Ethylene oxide exposure may increase the oxide. N Engl J Med 1991; 324: 1402–7. risk of spontaneous abortion, preterm birth, and postterm birth. Dimethylene oxide; Epoxietano; 1,2-Epoxyethane; Etylenu 2. Stayner L, et al. Exposure-response analysis of cancer mortality Epidemiology 1996; 7: 363–8. tlenek; Óxido de etileno; Oxirane; Oxirano; Oxirano. in a cohort of workers exposed to ethylene oxide. Am J Epidemi- ol 1993; 138: 787–98. Окись Этилена; Этиленоксид 3. Steenland K, et al. Mortality analyses in a cohort of 18 235 eth- Pharmacokinetics C2H4O = 44.05. ylene oxide exposed workers: follow up extended from 1987 to Ethylene oxide gas is rapidly absorbed through the CAS — 75-21-8. 1998. Occup Environ Med 2004; 61: 2–7. lungs and distributed throughout the body. Percutane- 4. IARC/WHO. Some industrial chemicals. IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans ous absorption can occur from aqueous solutions. It is volume 60 1994. Available at: http://monographs.iarc.fr/ENG/ rapidly metabolised by hydrolysis or conjugation with O Monographs/vol60/volume60.pdf (accessed 23/05/06) 5. Coggon D, et al. Mortality of workers exposed to ethylene oxide: glutathione. extended follow up of a British cohort. Occup Environ Med 2004; 61: 358–62. Uses Description. Ethylene oxide is a colourless flammable gas at 6. Steenland K, et al. Ethylene oxide and breast cancer incidence in Ethylene oxide is a bactericidal and fungicidal gaseous room temperature and atmospheric pressure. a cohort study of 7576 women (United States). Cancer Causes Control 2003; 14: 531–9. disinfectant that is effective against most micro-organ- Stability. Mixtures of ethylene oxide with oxygen or air are ex- isms, including viruses. It is also sporicidal. It is used plosive but the risk can be reduced by the addition of carbon di- Effects on the nervous system. Four men exposed to ethyl- oxide or fluorocarbons. ene oxide at a concentration of greater than 700 ppm developed for the gaseous sterilisation of heat-labile pharmaceuti- neurological disorders. One experienced headaches, nausea, cal and surgical materials that cannot be sterilised by vomiting, and lethargy followed by major motor seizures. The other means. Adverse Effects and Precautions others had headaches, limb numbness and weakness, increased Ethylene oxide irritates the eyes and respiratory tract fatigue, trouble with memory and thought processes, and slurred Ethylene oxide forms explosive mixtures with air; this and may also cause nausea and vomiting, diarrhoea, speech. Three also developed cataracts, and one required bilater- may be overcome by using mixtures containing 10% headache, vertigo, CNS depression, dyspnoea, and al cataract extractions.1 Rash, followed a few months later by ethylene oxide in carbon dioxide, or by removing at hand numbness and weakness, headaches, and cognitive impair- pulmonary oedema. Liver and kidney damage and ment, has been reported2 in a cluster of 12 surgical nurses and least 95% of the air from the apparatus before admit- haemolysis may occur. Fatalities have occurred. Ex- technicians after exposure for 5 months to ethylene oxide-con- ting either ethylene oxide or a mixture of 90% ethylene cessive exposure of the skin to liquid or solution causes taminated surgical gowns. Several patients showed signs of oxide in carbon dioxide. Alternatively, non-flammable The symbol † denotes a preparation no longer actively marketed The symbol ⊗ denotes a substance whose use may be restricted in certain sports (see p.vii)