WORKSHOP ON NICKEL DERMATITIS: FACTS, UNDERSTANDING, AND PREVENTION

Transcription

1 WORKSHOP ON NICKEL DERMATITIS: FACTS, UNDERSTANDING, AND PREVENTION Nickel Sensitization Process, Data Overview and Research Katherine Heim, PhD, DABT Regulatory Toxicologist, NiPERA Inc. /Nickel Institute Chicago, 23 June 2016

2 1. Mechanism of nickel sensitization 2. Potency of nickel as an allergen 3. Oral elicitation of nickel allergic dermatitis 4. Nickel in materials 5. Existing information 6. Ongoing research 79

3 NACD (Nickel Allergic Contact Dermatitis) Nickel is naturally-occurring, and is essential to all plants and some animals Approximately 12-15% of women and 1-2% of men are sensitized to nickel NACD is not life threatening, although it may cause pain and discomfort Nickel Institute believes that communication of information about nickel sensitization (nickel allergy) and NACD is important for understanding and prevention Nickel Institute s website contains freely available information on nickel sensitization and NACD Communication about nickel allergy and NACD will help prevent them 80

4 Sensitization Mechanism Nickel sensitization is the condition of being allergic to nickel Detected by patch testing NACD reactions occur in nickel-sensitized (or nickel allergic) individuals Determined by relevance data Nickel sensitization and NACD can be prevented by avoiding direct and prolonged contact with items that could potentially release a sufficient amount of nickel to cause sensitization or a NACD reaction. Three conditions must be true for NACD to occur: Direct contact Prolonged contact Sufficient amount of nickel ions released 81

5 Sensitization Mechanism- Direct Contact Direct contact with the skin by a nickel-releasing material is needed in order for the nickel ions to cross the skin barrier and cause an allergic reaction Nickel Sensitization is a Type IV Allergy: Induction phase primes and sensitizes the immune system for an allergic response above a threshold Creates memory of nickel as an allergen for future exposure Non-reversible effect (once allergic likely to continue to be allergic) o Low oral doses have been shown to increase amount needed for nickel allergy (threshold) Elicitation phase when this response is triggered Immune system recognizes nickel and causes NACD reaction Reversible reaction (allergic reaction heals after exposure stops) Both phases require nickel ions to cross the epidermis into the dermis to cause an immune reaction Does not cause anaphylactic shock like some other types of allergies (type I, II, or III) to common allergens (e.g. food allergens, wasp stings) Direct contact is needed for a NACD reaction 82

6 Sensitization Mechanism- Type IV Allergy Induction phase Elicitation phase 83

7 Sensitization Mechanism- Skin Anatomy 84

8 Sensitization Mechanism- Prolonged Contact For metallic articles, corrosion is needed for nickel ions to be released and induction of nickel sensitization or NACD to occur. Prolonged contact of the nickel-containing material with the skin is needed for sufficient nickel ions to be generated and penetrate skin (become bioavailable) to cause nickel sensitization or NACD: Corrosion requires a medium (e.g. sweat, water) for reaction to occur Time is needed for each of these steps: corrosion dissolving of corrosion products skin absorption of nickel ions Prolonged contact is needed for release of nickel ions 85

9 Sensitization Mechanism- Sufficient Nickel Ions Sufficient amount of nickel ions to be above the threshold (for induction or elicitation) is needed for nickel sensitization or NACD to occur Threshold is lower for elicitation phase than induction phase Less nickel ions needed to cause a dermatitis reaction in nickel-allergic individuals than for a non-nickel-allergic individuals to become nickelallergic Prevention of dermatitis in nickel-allergic individuals will protect nonnickel allergic individuals from becoming allergic to nickel [Ni 2+ ] > threshold = NACD Prolonged contact is needed for release of nickel ions. 86

10 Potency of Nickel as an Allergen Nickel is considered to be a weak sensitizer Threshold exposure to cause NACD reaction (induction or elicitation) is relatively weak compared to other allergens Prevalence of nickel allergy in general population is due to frequency and type of exposure to nickel-releasing materials (e.g. jewelry), not to the high strength of nickel as an allergen Potency of nickel as a skin allergen is weak. 87

11 Oral elicitation of nickel allergic dermatitis Small number of nickel-allergic individuals react to high levels of nickel when ingested orally (drink or food). 1% of nickel-allergic patients estimated to have a cutaneous reaction to 220 ug Ni/day Mean [nickel] in typical US diet = ug/d Low nickel diets have proved beneficial for these individuals Variety of diets exist Exclude nuts, oats, chocolate, coffee, and items containing nickel in levels higher than other foods Small number of nickel patients react to ingested nickel 88

12 Nickel in Materials Some nickel-containing materials are safe for use in direct and prolonged contact with the skin. Nickel release (not content) is relevant for assessing potential to cause NACD Sensitization and NACD requires nickel ion release in a sufficient amount to exceed the threshold for sensitization or elicitation reactions Nickel containing materials may not release significant amounts of nickel (e.g. most stainless steels, some coated materials) Stainless steels containing 9-28% nickel are used for making high quality watches Recent study of chromium-plated nickel passed EN after wear test (EN12472:2005) Reason for change in Nickel Directive from nickel content to nickel release rate for piercing materials in Nickel-containing materials can be used safely. 89

13 Existing Information on NACD Most science of nickel sensitization and NACD is well established Unknown time needed for continuous contact with high nickelreleasing item to develop nickel allergic reaction (definition of prolonged contact) NiPERA research project ongoing to address this issue 90

14 Ongoing Research Definition of prolonged skin contact: NiPERA Scientific Research Project ECHA definition of prolonged skin contact based on currently available information- not sufficient to accurately determine definition of prolonged contact for NACD NiPERA initiated research with Dr. Rosemary Nixon (dermatologist) to determine the amount of time needed to elicit a dermal reaction in nickel-sensitized individuals. Phase 1 started in 2015 Draft report received Spring 2016 Results will be presented at ESCD 2016 meeting (Sept.) Phase 2 to start Summer 2016 Patch testing discs to be made of nickel-plated brass Testing of 25 nickel-sensitized individuals 91

15 Definition of prolonged skin contact research project- Phase 1 Methods: Nickel-sensitized subjects recruited from patch test database (Patchcams) Ages years old 3 men, 16 women NiSO4 patch test reactivity representative of whole database (n=1244) Patch testing for 48 hours of subjects NiSO4 patch tests Ni discs patch tests ( >99.9% Ni) Empty Finn chambers as controls Patch test times for nickel discs and Finn chamber controls One time for 30 minutes, 1 hour or 2 hours 3 times in 2 weeks for 10, 30, or 60 minutes Readings performed double-blind by a dermatologist EN1811:2011+A1:2015 testing: Tested for total patch test times + longer times 10 and 30 minutes; 1, 2, 8, 12, 24, 48, 120, 144, 168 hours 5 discs/time point DMG testing on 55 nickel discs 92

16 Definition of prolonged skin contact research project- Phase 1 Preliminary results: 48 hour patch testing All subjects were NiSO 4 patch test positive 14/18 subjects Ni disc patch test positive Only 1 subject had clear reaction to Ni discs +++ NiSO 4 patch test reaction Weak reaction (+) at 48 hours after 3 rd repetition of 30 minutes Reactions (+-+++) at 30 minutes, 60 minutes, and 2 hours single applications 2 subject had inconsistent reactions Weak reactions (+) after 2 nd repetition of 60 minutes No reactions to longer times 1 subject had equivocal reactions EN1811:2011+A1:2015 testing: Tested for total patch test times + longer times 10 and 30 minutes; 1, 2, 8, 12, 24, 48, 120, 144, 168 hours 5 discs/time point 10 minutes 3/5 compliant (meets Ni restriction limit) All other time points non-compliant (exceeds Ni restriction limit) DMG test on nickel discs 39/55 (71%) tested positive (16/55 = 29% negative) Final results to be shared with regulatory authorities (for consideration in the context of current definition of prolonged contact) and published in a peer-reviewed journal 93

17 NACD- Nickel Institute Communications Publications: Nickel Allergic Contact Dermatitis Fact Sheet available on NiPERA website AllergicContactDermatitis.aspx Detailed information on NACD Updated as needed Infographic on NACD available on Nickel Institute website Easy to read format with key information Available on NI website and will be distributed to relevant audiences Communication documents created to help understanding of nickel allergy 94

18 NACD- Infographic 95

19 Summary NACD causes discomfort but is not life-threatening Nickel allergy and NACD can be prevented through control of exposure to high nickel-releasing items Nickel release is the relevant measure to assess potential to cause nickel allergy and NACD Reduction of nickel allergy and management of NACD is possible by use of appropriate materials, e.g. low nickel-releasing articles for items in direct and prolonged contact with the skin NACD is preventable through selection of appropriate materials 96

20 Katherine Heim, PhD, DABT