©fioh, riitta jolanki 27-28.8.2003 allergic contact dermatitis the most common allergens riitta...

©FIOH, Riitta Jolanki27-28.8.2003

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

[email protected]


Most common causes of allergic contact dermatitis

rubber chemicals, e.g. accelerators and antioxidants plastic chemicals

– epoxy and acrylic compounds, phenol-formaldehyde resins metals and their compounds

– nickel, cobalt, chromium compounds

– gold, mercury formaldehyde and other antimicrobials

– formaldehyde, formaldehyde releasers

– isothiazolinones, dibromo dicyanobutane

– glutaraldehyde colophony


Rubber and rubber chemicals


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%

Antimicrobials 10%

Others 28%


Rubber

natural rubber latex

– isoprene synthetic rubber

– isoprene

– nitrile

– neoprene or chloroprene

– butyl

– styrenebutadiene

accelerators

– thiuram mix and mercapto mix component

– thioureas, dithiocarbamates

antioxidants

– PPD-mix components (IPPD, CPPD, DPPD)

vulcanizers retarders plasticizers filling agents, dyes

RUBBER CHEMICALSRUBBER POLYMER +


Exposure to rubber chemicals

Occupational

– rubber manufacture

– rubber gloves (> 80% of cases)

– rubber boots, rubber grips of tools, cable materials, tires, etc.

Clothing

– shoes, boots, socks, stockings, waistbands, etc.

Health care

– tubes, bandages, catheters, etc. Condoms


Allergic rubber dermatitis

12% of all occupational dermatoses are caused by rubber and rubber chemicals 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.) Contact urticaria / protein contact dermatitis (30% of occupational rubber dermatoses)

– due to immediate allergic reaction

– proteins in natural rubber latex (NRL)


Incidence rates of occupational contact urticaria caused by natural rubber latex

(1991-1996, cases/100,000 worker years)

Dental assistants 118 Dentists 60 Physicians 39 Nurses 22

Laboratory assistants 10 Cleaners 5

ALL OCCUPATIONS 2


Occupational contact urticaria caused by natural rubber latex (NRL) proteins

An occupational skin disease caused mostly by protective gloves used by health care workers

Dental assistants and dentists are at highest risk

The risk of cleaners is not very high despite frequent use of protective NRL gloves


Plastic chemicals


Occupational allergic contactdermatitis by cause in 1990-96

(N = 2 647 cases)

rubber chemicals 26%

plastic chemicals 21%

metals (Ni, Cr, Co, Hg, Au) 15%

antimicrobials 10%

others 28%


Finished plastic materials are mixtures

Polymer molecules (e.g. PVC)

–may contain remnants of raw material (e.g., monomers) and additives used in polymerization process

Additives (e.g., phthalates)


Sensitizing plastic chemicals 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. 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.


Contact allergy caused by finished plastic products

Uncommon May develop after prolonged or

repeated skin contact (e.g., using of plastic gloves)


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 resins 109 cases

Other plastic chemicals 63 cases


Epoxy resin system

Epoxy resin Hardener Reactive diluents Other additives

epoxy resincompounds


Two-component epoxy resin products

•Hardener

(e.g. polyamines)

•Additives

•Epoxy resin

•Reactive diluents

•Additives


One-component epoxy resin products

•Epoxy resin

•Reactive diluent

•Additives

(e.g. phthalic anhydrides)

•Latent hardener + heat


DGEBA epoxy resin

About 75 % of the epoxy resins used worldwide are of DGEBA type

Reaction product of bisphenol-A and epichlorohydrin DGEBA (MW 340) and larger molecules (up to over MW 8000)

DGEBA (MW 340) is the strongest allergen

O

CHCH2Epoxy group


C

CH3

CH3

C

CH3

CH3n

O

OH

CH2CHCH2OOCH2 CH

O

CH2

DGEBA epoxy resin

CH CH2

O

CH2

2

epichlorohydrinbisphenol A

+ CH2Cl

O

CHCH2OH

CH3

CH3

CHO

O


Liquid epoxy resin

Contains mostly sensitizing DGEBA molecules (MW 340)

Solid epoxy resin Contains low amounts of sensitizing DGEBA

molecules (MW 340)


Properties possessed by epoxy resins

Easy cure High adhesive strength High electrical insulation Good resistance against water,

chemicals, corrosion, heat and abrasion

Low shrinkage Expensive


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


Occupational allergic contact dermatitis from epoxy resin

compounds at FIOHin 1974-95 (N = 182)

DGEBA epoxy resins 80%

non-DGEBA epoxy resins 9%

polyamine hardeners (PA) 23%

reactive diluents (RD) 16%

simultaneous contact allergy 30%


Epoxy resin compounds

Roughly 1% of the exposed workers in Finland annually develop allergic contact dermatitis


Patch testing

No single chemical alone (i.e. standard DGEBA epoxy resin) can screen for epoxy sensitization

Isolated or simultaneous contact allergies to other epoxy resin compound

– polyamine hardeners

– reactive diluents

– non-DGEBA epoxy resins New allergens in patients’ own materials



1990-96 (N = 557 cases)






Sensitizing acrylic compounds Methacrylates, e.g.,

– 2-HEMA (2-hydroxyethyl methacrylate)

– TEGDMA (triethylenegkycol dimethacrylate)

– MMA (methyl methacrylate)

– BIS-GMA (epoxy dimethacrylate) Acrylates, e.g.,

– EA (ethyl acrylate)

– BIS-GA (epoxy diacrylate) Cyanoacrylates

– ethylcyanoacrylate


Use of (meth)acrylates and cyanoacrylates

Dental composite restorative materials, dental sealants and dental coatings

Manufacture of dentures, bone cements, hearing aids

Anaerobic sealants (Loctite, screw-thread locking)

Instant glues (cyanoacrylates) UV-reactive inks, printing plates of

photoprepolymer type and coatings Manufacture of circuit board Nail cosmetics, etc.


Occupations at risk - acrylic compound

Dental nurses Dentists Dental technicians Plumbers Machinists Machine and metal product

assemblers Electrical and teletechnical

equipment assemblers Printers Beauticians



1990-96 (N = 557 cases)






Formaldehyde-based resins 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)

Urea-formaldehyde resins (CA to formaldehyde)

– textile finishing resin

– chipboard glues

–wood glue industry


Non-occupational exposure to allergenic plastic materials

Two-component paints, lacquers and glues (epoxy compounds), and two-component cements (polyesters)

Contact adhesives (phenol-formaldehyde resin) and instat glues (cyanoacrylate)

Anaerobic acrylic sealants (methacrylates) Dental fillings and prosthesis (methacrylates) Clothing (textile resins; formaldehyde) Nail cosmetics (lacquers, sculptured nail materials and

artificial-tip glues; acrylic compounds) Plastic gloves and spectacle frames (plastisizers)


Metals and metal compounds



(N = 2 647 cases)




Antimicrobials 10%

Others 28%


Metals and metal compounds

Most common sensitizers

– nickel

– cobalt

– chromium compounds Uncommon sensitizers

– gold

–mercury


Statistics of the Finnish Institute of Occupational

Health (FIOH)

10–15% of all occupational skin diseases diagnosed in Finland


Skin diseases(FIOH, 1991-1999)

1893 patients examined 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


Occupational ACD caused by other metals (FIOH)

Gold (2 cases)

– dental nurse (gold sanding dust)

–metal worker (gold-plating solutions and metallic gold)

Mercury (2 cases)

– chemistry student (laboratory chemicals)

– dentist (metallic mercury from amalgam)


Chromium compounds

Chromium metal itself does not cause sensitizing Chrome-tanned leather (water-soluble chromium III

compounds)

– tanning work; leather gloves; shoes etc. 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

Chromate-coating solutions Wood material preserved with chrome salts Metal-working fluids being in use Printing inks, paints


Cobalt

Cobalt metal itself and its salts may cause sensitizing Minor element in nickel compounds Hard metal (2–39% Co), stellite (60% Co) and metal dusts Metal salts of electroplating Metal-working fluids Accelerator or catalyst of polyester or acrylate resin

systems Dryers in oil-based paints, lacquers, printing inks Cement and pottery clay Cobalt dyes Animal feed enriched with cobalt salts


Nickel Nickel metal itself and its salts may cause

sensitizing 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.

Stainless steels such as 18/8 (18% Ni) are generally safe at skin contact

Electrical equipment Machines Metal-working fluids


Nickel Directive

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)

The limit value for nickel release is 0.5 µg/cm² per week

Nickel is not restricted in other type of items


Nickel test

Dimethylglyoxime (DMG) test Simple to use 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


Occupational ACD from metals - concluding remarks

chromium

– chrome-tanned leather – cement-based products

nickel

– contact allergy from non-occupational exposure, and then dermatitis from occupational exposure

cobalt

– hard metals, stellite

– polyester resin accelerators occupational ACD from other metals

– uncommon


Occupations at risk - nickel, cobalt and chromium

Nickel

– platers

– electronic industry asseblers

– metalworkers

– hairdressers

– cashiers Cobalt

– metal smelting workers

– machinists Chromium

– construction workers

– leather tanners

– metal workers (chromate-plating)


Formaldehyde and other antimicrobials



(N = 2 647 cases)




Antimicrobials 10%

Others 28%


Most common sensitizing antimicrobials

Formaldehyde Formaldehyde releasers Methyl(chloro)isothiazolinones

– Methylchloroisothiazolinone (and) Methylisothiazolinone*

– Kathon CG

– Euxyl K 100 Dibromo dicyanobutane

– Methyldibromo Glutaronitrile*

– Euxyl K 400

– Tektamer 38) Glutaraldehyde

*INCI = International Nomenclature of Cosmetic Ingredients


Formaldehyde releasers in cosmetics

Chemical itself and released formaldehyde can cause sensitization

Imidazolidinyl urea* (Germall 115) Diazolidinyl urea* (Germall II) 2-Bromo-2-nitropropane-1,3-diol* (Bronopol) Chloroallylhexaminium chloride (Quaternium-15*,

Dowicil 200) DMDM hydantoin* Benzylhemiformal* (Akyposept B) Methenamine* Tris(hydroxymethyl)nitromethane*

*INCI = International Nomenclature of Cosmetic Ingredients


Formaldehyde and other antimicrobials - exposure

Formaldehyde-based resins

– urea, phenolic and melamine resins (manufacture, glues)

– chipboards (ureaformaldehyde resin)

– textile finishing (permanent press and waterproof fabrics) 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.


Colophony


Colophony Colophonium; rosin; gum, wood and pine rosin; tall oil rosin contain 80–90% rosin acids (e.g., abietic acid) Obtained from coniferous tree 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

©fioh, riitta jolanki 27-28.8.2003 allergic contact dermatitis the most common allergens riitta...

Documents

allergic rubber dermatitis

occupational rubber

cases rubber chemicals

cases rubber boots

natural rubber latex

synthetic rubber nitrile

natural rubber latex

rubber grips of tools