1. ©FIOH, Riitta Jolanki 27-28.8.2003 Allergic contact dermatitis  the most common allergens Riitta Jolanki, D.Tech. (Chem.Eng.), Docent Senior Research Scientist, Dermatotoxicologist Finnish Institute of Occupational Health (FIOH) Department of Occupational Medicine Section of Dermatology riitta.jolanki@ttl.fi

2. ©FIOH, Riitta Jolanki 27-28.8.2003 Most common causes of allergic contact dermatitis l rubber chemicals, e.g. accelerators and antioxidants l plastic chemicals –epoxy and acrylic compounds, phenol-formaldehyde resins l metals and their compounds –nickel, cobalt, chromium compounds –gold, mercury l formaldehyde and other antimicrobials –formaldehyde, formaldehyde releasers –isothiazolinones, dibromo dicyanobutane –glutaraldehyde l colophony

3. ©FIOH, Riitta Jolanki 27-28.8.2003 Rubber and rubber chemicals

4. ©FIOH, Riitta Jolanki 27-28.8.2003 Occupational allergic contact dermatitis by cause in 1990-96 (N = 2 647 cases) Rubber chemicals 26% Plastic chemicals 21% Metals (Ni, Cr, Co, Hg, Au) 15% Antimicrobials10% Others 28%

5. ©FIOH, Riitta Jolanki 27-28.8.2003 Rubber l natural rubber latex –isoprene l synthetic rubber –isoprene –nitrile –neoprene or chloroprene –butyl –styrenebutadiene l accelerators –thiuram mix and mercapto mix component –thioureas, dithiocarbamates l antioxidants –PPD-mix components (IPPD, CPPD, DPPD) l vulcanizers l retarders l plasticizers l filling agents, dyes RUBBER CHEMICALSRUBBER POLYMER +

6. ©FIOH, Riitta Jolanki 27-28.8.2003 Exposure to rubber chemicals l Occupational –rubber manufacture –rubber gloves (> 80% of cases) –rubber boots, rubber grips of tools, cable materials, tires, etc. l Clothing –shoes, boots, socks, stockings, waistbands, etc. l Health care –tubes, bandages, catheters, etc. l Condoms

7. ©FIOH, Riitta Jolanki 27-28.8.2003 Allergic rubber dermatitis l 12% of all occupational dermatoses are caused by rubber and rubber chemicals l Allergic contact dermatitis (70% of occupational rubber dermatoses) –due to delayed allergic reaction –rubber chemicals in natural rubber and in synthetic rubber (nitrile, neoprene, etc.) l Contact urticaria / protein contact dermatitis (30% of occupational rubber dermatoses) –due to immediate allergic reaction –proteins in natural rubber latex (NRL)

8. ©FIOH, Riitta Jolanki 27-28.8.2003 Incidence rates of occupational contact urticaria caused by natural rubber latex (1991-1996, cases/100,000 worker years) l Dental assistants118 l Dentists 60 l Physicians 39 l Nurses 22 l Laboratory assistants 10 l Cleaners 5 l ALL OCCUPATIONS 2

9. ©FIOH, Riitta Jolanki 27-28.8.2003 Occupational contact urticaria caused by natural rubber latex (NRL) proteins l An occupational skin disease caused mostly by protective gloves used by health care workers l Dental assistants and dentists are at highest risk l The risk of cleaners is not very high despite frequent use of protective NRL gloves

10. ©FIOH, Riitta Jolanki 27-28.8.2003 Plastic chemicals

11. ©FIOH, Riitta Jolanki 27-28.8.2003 Occupational allergic contact dermatitis by cause in 1990-96 (N = 2 647 cases) rubber chemicals 26% plastic chemicals 21% metals (Ni, Cr, Co, Hg, Au) 15% antimicrobials10% others 28%

12. ©FIOH, Riitta Jolanki 27-28.8.2003 Finished plastic materials are mixtures l Polymer molecules (e.g. PVC) –may contain remnants of raw material (e.g., monomers) and additives used in polymerization process l Additives (e.g., phthalates)

13. ©FIOH, Riitta Jolanki 27-28.8.2003 Sensitizing plastic chemicals l Uncured plastic materials, and handling of resins or resin- based products, such as two-component paints and glues –raw materials (monomers) –synthetic resins (prepolymers), e.g., epoxy resins –hardeners –rective diluents –accelerators, catalysts, etc. l Finished plastic products –remnants of monomers, synthetic resins, hardeners, etc. –inert additives (plastisizers, dyes, etc.) –chemicals released during working the plastic material –chemicals released during decomposition by high temperature, moisture, etc.

14. ©FIOH, Riitta Jolanki 27-28.8.2003 Contact allergy caused by finished plastic products l Uncommon l May develop after prolonged or repeated skin contact (e.g., using of plastic gloves)

15. ©FIOH, Riitta Jolanki 27-28.8.2003 Occupational allergic contact dermatitis from plastic chemicals in 1990-96 (N = 557 cases) Epoxy resin compounds 250 cases Acrylates and methacrylates 135 cases Formaldehyde-based resins109 cases Other plastic chemicals 63 cases

16. ©FIOH, Riitta Jolanki 27-28.8.2003 Epoxy resin system l Epoxy resin l Hardener l Reactive diluents l Other additives epoxy resin compounds

17. ©FIOH, Riitta Jolanki 27-28.8.2003 Two-component epoxy resin products  Hardener (e.g. polyamines) Additives Epoxy resin Reactive diluents Additives

18. ©FIOH, Riitta Jolanki 27-28.8.2003 One-component epoxy resin products Epoxy resin Reactive diluent Additives (e.g. phthalic anhydrides) Latent hardener + heat

19. ©FIOH, Riitta Jolanki 27-28.8.2003 DGEBA epoxy resin l About 75 % of the epoxy resins used worldwide are of DGEBA type l Reaction product of bisphenol-A and epichlorohydrin  DGEBA (MW 340) and larger molecules (up to over MW 8000) l DGEBA (MW 340) is the strongest allergen O CHCH 2 Epoxy group

20. ©FIOH, Riitta Jolanki 27-28.8.2003

21. ©FIOH, Riitta Jolanki 27-28.8.2003 Liquid epoxy resin l Contains mostly sensitizing DGEBA molecules (MW 340) Solid epoxy resin l Contains low amounts of sensitizing DGEBA molecules (MW 340)

22. ©FIOH, Riitta Jolanki 27-28.8.2003 Properties possessed by epoxy resins l Easy cure l High adhesive strength l High electrical insulation l Good resistance against water, chemicals, corrosion, heat and abrasion l Low shrinkage l Expensive

23. ©FIOH, Riitta Jolanki 27-28.8.2003 Use of epoxy resins l Two-component paints and other coatings l Two-component glues l Electrical insulation materials l Manufacture of glass-fiber (sizing) l Manufacture of sporting goods, e.g. skis l Concrete injection resin (repairing) l Lamination work and prepreg-laminates l Powder paints l Microscopy immersion oil l Nail cosmetics l Medical devices

24. ©FIOH, Riitta Jolanki 27-28.8.2003 Occupational allergic contact dermatitis from epoxy resin compounds at FIOH in 1974-95 (N = 182) DGEBA epoxy resins 80% non-DGEBA epoxy resins 9% polyamine hardeners (PA)23% reactive diluents (RD)16% simultaneous contact allergy30%

25. ©FIOH, Riitta Jolanki 27-28.8.2003 Epoxy resin compounds l Roughly 1% of the exposed workers in Finland annually develop allergic contact dermatitis

26. ©FIOH, Riitta Jolanki 27-28.8.2003 Patch testing l No single chemical alone (i.e. standard DGEBA epoxy resin) can screen for epoxy sensitization l Isolated or simultaneous contact allergies to other epoxy resin compound –polyamine hardeners –reactive diluents –non-DGEBA epoxy resins l New allergens in patients’ own materials

27. ©FIOH, Riitta Jolanki 27-28.8.2003 Occupational allergic contact dermatitis from plastic chemicals in 1990-96 (N = 557 cases) Epoxy resin compounds 250 cases Acrylates and methacrylates 135 cases Formaldehyde-based resins109 cases Other plastic chemicals 63 cases

28. ©FIOH, Riitta Jolanki 27-28.8.2003 Sensitizing acrylic compounds l Methacrylates, e.g., –2-HEMA (2-hydroxyethyl methacrylate) –TEGDMA (triethylenegkycol dimethacrylate) –MMA (methyl methacrylate) –BIS-GMA (epoxy dimethacrylate) l Acrylates, e.g., –EA (ethyl acrylate) –BIS-GA (epoxy diacrylate) l Cyanoacrylates –ethylcyanoacrylate

29. ©FIOH, Riitta Jolanki 27-28.8.2003 Use of (meth)acrylates and cyanoacrylates l Dental composite restorative materials, dental sealants and dental coatings l Manufacture of dentures, bone cements, hearing aids l Anaerobic sealants (Loctite, screw-thread locking) l Instant glues (cyanoacrylates) l UV-reactive inks, printing plates of photoprepolymer type and coatings l Manufacture of circuit board l Nail cosmetics, etc.

30. ©FIOH, Riitta Jolanki 27-28.8.2003 Occupations at risk - acrylic compound l Dental nurses l Dentists l Dental technicians l Plumbers l Machinists l Machine and metal product assemblers l Electrical and teletechnical equipment assemblers l Printers l Beauticians

31. ©FIOH, Riitta Jolanki 27-28.8.2003 Occupational allergic contact dermatitis from plastic chemicals in 1990-96 (N = 557 cases) Epoxy resin compounds 250 cases Acrylates and methacrylates 135 cases Formaldehyde-based resins109 cases Other plastic chemicals 63 cases

32. ©FIOH, Riitta Jolanki 27-28.8.2003 Formaldehyde-based resins l Phenol-formaldehyde resins (CA to resin or formaldehyde) –plywood adhesives and glue films –mineral wool resin –mold core resins (metal industry) –neoprene contact adhesives (e.g., leather adhesives) l Urea-formaldehyde resins (CA to formaldehyde) –textile finishing resin –chipboard glues –wood glue industry

33. ©FIOH, Riitta Jolanki 27-28.8.2003 Non-occupational exposure to allergenic plastic materials l Two-component paints, lacquers and glues (epoxy compounds), and two-component cements (polyesters) l Contact adhesives (phenol-formaldehyde resin) and instat glues (cyanoacrylate) l Anaerobic acrylic sealants (methacrylates) l Dental fillings and prosthesis (methacrylates) l Clothing (textile resins; formaldehyde) l Nail cosmetics (lacquers, sculptured nail materials and artificial-tip glues; acrylic compounds) l Plastic gloves and spectacle frames (plastisizers)

34. ©FIOH, Riitta Jolanki 27-28.8.2003 Metals and metal compounds

35. ©FIOH, Riitta Jolanki 27-28.8.2003 Occupational allergic contact dermatitis by cause in 1990-96 (N = 2 647 cases) Rubber chemicals 26% Plastic chemicals 21% Metals (Ni, Cr, Co, Hg, Au) 15% Antimicrobials10% Others 28%

36. ©FIOH, Riitta Jolanki 27-28.8.2003 Metals and metal compounds l Most common sensitizers –nickel –cobalt –chromium compounds l Uncommon sensitizers –gold –mercury

37. ©FIOH, Riitta Jolanki 27-28.8.2003 Statistics of the Finnish Institute of Occupational Health (FIOH) l 10–15% of all occupational skin diseases diagnosed in Finland

38. ©FIOH, Riitta Jolanki 27-28.8.2003 Skin diseases (FIOH, 1991-1999) l 1893 patients examined l 558 patients diagnosed as having occupational ACD –78 cases (14.0%) from chromium, nickel and cobalt and their compounds –2 cases from gold –2 cases from mercury

39. ©FIOH, Riitta Jolanki 27-28.8.2003 Occupational ACD caused by other metals (FIOH) l Gold (2 cases) –dental nurse (gold sanding dust) –metal worker (gold-plating solutions and metallic gold) l Mercury (2 cases) –chemistry student (laboratory chemicals) –dentist (metallic mercury from amalgam)

40. ©FIOH, Riitta Jolanki 27-28.8.2003 Chromium compounds l Chromium metal itself does not cause sensitizing l Chrome-tanned leather (water-soluble chromium III compounds) –tanning work; leather gloves; shoes etc. l Cement-based products –in Finland since 1987 the amount of sensitizing hexavalent chromium compounds has been reduced by adding ferrous sulfate to the cement  insoluble non-sensitizing trivalent chromiumI compounds l Chromate-coating solutions l Wood material preserved with chrome salts l Metal-working fluids being in use l Printing inks, paints

41. ©FIOH, Riitta Jolanki 27-28.8.2003 Cobalt l Cobalt metal itself and its salts may cause sensitizing l Minor element in nickel compounds l Hard metal (2–39% Co), stellite (60% Co) and metal dusts l Metal salts of electroplating l Metal-working fluids l Accelerator or catalyst of polyester or acrylate resin systems l Dryers in oil-based paints, lacquers, printing inks l Cement and pottery clay l Cobalt dyes l Animal feed enriched with cobalt salts

42. ©FIOH, Riitta Jolanki 27-28.8.2003 Nickel l Nickel metal itself and its salts may cause sensitizing l Nickel-containing metals (nickel-silver, copper- nickel, nickel-brass, some white gold alloys), and nickel-plated items –tools, scissors, keys, coins, pens, needles, musical instruments, etc. l Stainless steels such as 18/8 (18% Ni) are generally safe at skin contact l Electrical equipment l Machines l Metal-working fluids

43. ©FIOH, Riitta Jolanki 27-28.8.2003 Nickel Directive l From 2001, the EU Nickel Directive limits nickel in items intended for direct and prolonged contact with skin (e.g., jewelry, watches, buttons, and spectacle frames) l The limit value for nickel release is 0.5 µg/cm² per week l Nickel is not restricted in other type of items

44. ©FIOH, Riitta Jolanki 27-28.8.2003 Nickel test l Dimethylglyoxime (DMG) test l Simple to use l Release of nickel ions is indicated by red or pink color (positive DMG test) after rubbing the surface with cotton wool-tipped stick soaked with drop of DMG and ammonia

45. ©FIOH, Riitta Jolanki 27-28.8.2003 Occupational ACD from m etals - concluding remarks l chromium –chrome-tanned leather  –cement-based products  l nickel –contact allergy from non-occupational exposure, and then dermatitis from occupational exposure l cobalt –hard metals, stellite –polyester resin accelerators l occupational ACD from other metals –uncommon

46. ©FIOH, Riitta Jolanki 27-28.8.2003 Occupations at risk - nickel, cobalt and chromium l Nickel –platers –electronic industry asseblers –metalworkers –hairdressers –cashiers l Cobalt –metal smelting workers –machinists l Chromium –construction workers –leather tanners –metal workers (chromate-plating)

47. ©FIOH, Riitta Jolanki 27-28.8.2003 Formaldehyde and other antimicrobials

48. ©FIOH, Riitta Jolanki 27-28.8.2003 Occupational allergic contact dermatitis by cause in 1990-96 (N = 2 647 cases) Rubber chemicals 26% Plastic chemicals 21% Metals (Ni, Cr, Co, Hg, Au) 15% Antimicrobials10% Others 28%

49. ©FIOH, Riitta Jolanki 27-28.8.2003 Most common sensitizing antimicrobials l Formaldehyde l Formaldehyde releasers l Methyl(chloro)isothiazolinones –Methylchloroisothiazolinone (and) Methylisothiazolinone* –Kathon CG –Euxyl K 100 l Dibromo dicyanobutane –Methyldibromo Glutaronitrile* –Euxyl K 400 –Tektamer 38) l Glutaraldehyde *INCI = International Nomenclature of Cosmetic Ingredients

50. ©FIOH, Riitta Jolanki 27-28.8.2003 Formaldehyde releasers in cosmetics l Chemical itself and released formaldehyde can cause sensitization l Imidazolidinyl urea* (Germall 115) l Diazolidinyl urea* (Germall II) l 2-Bromo-2-nitropropane-1,3-diol* (Bronopol) l Chloroallylhexaminium chloride (Quaternium-15*, Dowicil 200) l DMDM hydantoin* l Benzylhemiformal* (Akyposept B) l Methenamine* l Tris(hydroxymethyl)nitromethane* *INCI = International Nomenclature of Cosmetic Ingredients

51. ©FIOH, Riitta Jolanki 27-28.8.2003 Formaldehyde and other antimicrobials - exposure l Formaldehyde-based resins –urea, phenolic and melamine resins (manufacture, glues) –chipboards (ureaformaldehyde resin) –textile finishing (permanent press and waterproof fabrics) l Formaldehyde, FA releasers or other antimicrobials –preservatives »cosmetics (e.g., creams, soaps, shampoos, skin cleansers) »barrier creams, massage lotions »cleaning agents, dishwashing liquids »slimicides in paper manufacture, offset printing, etc. »water-based industrial chemicals (e.g., paints, adhesives/glues, metal-working fluids) –disinfectants in medical field –photographic chemicals, etc.

52. ©FIOH, Riitta Jolanki 27-28.8.2003 Colophony

53. ©FIOH, Riitta Jolanki 27-28.8.2003 Colophony l Colophonium; rosin; gum, wood and pine rosin; tall oil rosin l contain 80–90% rosin acids (e.g., abietic acid) l Obtained from coniferous tree l Can be found in the following products –wood and gum from pine tree (forest work, sawmills) –adhesives, glues, and tapes; plaster and adhesive bandages –printing inks –some paints and lacquers; polishes –metal working fluids –soldering fluxes and tin (core) –cosmetics (mascara and depilatory waxes –some dental materials (Duraphat lacquer) –dancers’ and string players’ rosins