Patch test results with serial dilutions of nickel sulfate (with and without detergent), palladium chloride, and nickel and palladium metal plates

Abstract

Clinical experience suggests the existence of different degrees of sensitivity in nickel-allergic patients. For quantification of this phenomenon, 462 consecutive patients with previously diagnosed or strongly suspected nickel allergy were tested with serial dilution patch tests with 5 ppm to 5% nickel sulfate in pet. (Ni), and 5 ppm to 1% nickel sulfate in pet. with 1% detergent (Ni/D). Additionally, nickel and palladium metal plates were tested in 103, and cobalt salts, dichromate and palladium chloride (PdCl2) in most patients. 332 patients reacted positively to Ni or Ni/D. The influence of a concomitantly administered detergent was not significant. A significant correlation was found between positive reactions to low concentrations of Ni (or Ni/D), i.e., 0.1% or less (N = 166), and concomitant reactions to nickel metal plates, cobalt salts and PdCl2 and a history of ear piercing with metal intolerance. The clinical relevance of reactions to PdCl2 is at present not clear. A subgroup of nickel-allergic patients with "high sensitivity" can be defined. In future studies further addressing the clinical relevance of high versus low sensitivity, patch testing with 0.01, 0.1, 1.0 and 5% nickel sulfate in pet. is recommended instead of routine tests with 5% only.

Proposal for a risk assessment methodology for skin sensitization based on sensitization potency data

“…Similar values of 0.018 and 0.035 nmol Ni/cm 2 are obtained on the basis of human data for nickel sulfate and nickel chloride, respectively, using considerably higher total EFs. The LLNA-based ANEAD is well supported by extensive human data on elicitation of nickel allergy: Several studies that used titration of nickel concentration on nickel-allergic subjects reported LOEL values between 21 and 0.90 nmol Ni/cm 2 (1.25 and 0.053 lg Ni/cm 2 ; see Table 7) (Allenby and Basketter, 1993;Hindsen et al, 1999;Menne, 1994;Uter et al, 1995). When patch testing was performed on detergent-compromised skin, i.e., forearm skin showing slight inflammation induced by repeated immersion of the arm into a commercial household detergent solution, a 10-fold lower LOEL of about 0.26 nmol Ni/cm 2 was observed (Allenby and Basketter, 1993).…”

“…, corresponding to an area dose of 165 lmol Ni/cm 2 Application of a total EF of 1000 results in ANSAD of 165 nmol Ni/cm 2 Derivation of ANSAD based HRIPT LOEL of 3.3% nickel sulfate a (Kligman, 1966), corresponding to an area dose of 2.6 lmol Ni/cm 2 Derivation of ANEAD based on LLNA EC3 of 2.5% (Ryan et al, 2002), corresponding to an area dose of 2400 nmol Ni/cm 2 Sensitization-elicitation EF 10^(0:84 Ã log(2.4) + 1.81) 135 Application of total EF of 40,500 results in ANEAD of 0.059 nmol Ni/cm 2 Derivation of ANEAD based on HRIPT LOEL of 25% nickel chloride (Vandenberg and Epstein, 1963), corresponding to an area dose of 165 lmol Ni/cm 2 Sensitization-elicitation EF 10^(0:84 Ã log(165) + 1.81) 4700 Derivation of ANEAD on based HRIPT LOEL of 1% nickel sulfate a (Kligman, 1966), corresponding to an area dose of 2.6 lmol Ni/cm 2 Sensitization-elicitation EF 10^(0:84 Ã log(2.6) + 1.81) 144 Application of total EF of 144,000 results in ANEAD of 0.018 nmol Ni/cm 2 Human experience (all studies used nickel sulfate) LOEL patch test (1.25 lg Ni/cm 2 ) (Menne, 1994) 21 nmol Ni/cm 2 LOEL patch test (0.21 lg Ni/cm 2 ) (Hindsen et al, 1999) (NOEL 0.07 lg/cm 2 ) 3.6 nmol Ni/cm 2 LOEL patch test (0.053 lg Ni/cm 2 ) (Uter et al, 1995) (NOEL 0.026 lg/cm 2 ) 0.90 nmol Ni/cm 2 LOEL patch test plus detergent b (0.026 lg Ni/cm 2 )(Uter et al, 1995) 0.44 nmol Ni/cm 2 LOEL patch test (0.15 lg Ni/cm 2 ) (Allenby and Basketter, 1993) (NOEL 0.05 lg/cm 2 ) 2.6 nmol Ni/cm 2 LOEL patch test on detergent-compromised skin c (0.015 lg Ni/cm 2 )(Allenby and Basketter, 1993) (NOEL 0.005 lg/cm 2 ) 0.26 nmol Ni/cm 2 LOEL patch test with nickel-containing alloys (stainless steel) d (0.002 lg Ni/cm 2 )(Menne et al, 1987) 0.034 nmol Ni/cm 2 EU nickel directive limits nickel-release from products, such as earrings, necklaces, bracelets, finger rings, wrist-watches, rivets and zippers to 0.5 lg/cm 2 /week(EU, 1994) 1.2 nmol Ni/cm 2 a SeeTable 2. b Test solution contained 1% of a commercial household detergent (aqueous solution of 25% alkyl benzenesulfonate and alkyl sulfonate plus 0.7% betaines).…”

Quantitative relationship between the local lymph node assay and human skin sensitization assays

“…Several reasons can be identified for ignoring potency considerations for sensitizers in current risk assessment frameworks. Despite clear scientific evidence for doseresponse relationships for both induction and elicitation of allergic skin reactions, effective doses vary substantially, due to considerable inter-individual differences in susceptibility (Jerschow et al, 2001;Robinson, 1999;Uter et al, 1995), and/or differences in exposure conditions, vehicle influences, and other factors modulating the severity of allergic symptoms (Felter et al, 2002). Furthermore, the guinea-pig models used for identifying skin sensitizers, i.e., the guinea-pig maximization test (GPMT) (Magnusson and Kligman, 1969) and the Buehler test (Buehler, 1965), are sensitive qualitative tests, well-established for decades, but do not allow for an objective measurement of potency.…”

Association of allergic contact dermatitis with a promoter polymorphism in the IL16 gene

“…2 For example, the concentrations of certain allergens needed to elicit contact allergic responses might differ between individuals by a factor of greater than 10,000. 3,4 The individual susceptibility has been attributed to genetic factors, such as carriage of certain HLA alleles. 5 However, the results of HLA allotype studies have remained largely inconclusive.…”