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Heavy Metal Index

Experimental systemic contact dermatitis from nickel: a dose-response study

Forty nickel-sensitive adults and 20 controls swallowed a single fasting dose of nickel sulfate hexahydrate at 0.3, 1.0, or 4.0 mg nickel, or a lactose placebo.

Forty nickel-sensitive adults and 20 controls swallowed a single fasting dose of nickel sulfate hexahydrate at 0.3, 1.0, or 4.0 mg nickel, or a lactose placebo. Skin reactions increased with dose among the nickel-sensitive group. Serum and urine were analysed before and one day after the dose. Many samples were below the printed detection limit of 0.12 mg/l. The authors report a dose-related rise after challenge, but the post-dose means are drawn in figures and are not printed as numbers.

Key numbers

Figures below are copied as printed. Units are not converted. Species are not merged.

AnalyteWhat was reportedValueUnitBasisWhere
Ni0.3, 1.0 or 4.0 mg nickel (given as nickel sulfate hexahydrate)0.3mg nickeloral dose, fasting, not a tissue concentrationOral exposures, p. 2
Ni1.0 mg nickel1.0mg nickeloral doseOral exposures, p. 2
Nioral exposure to 4.0 mg nickel4.0mg nickeloral doseAbstract, p. 1
Nijust lactose as placebo0mg nickel addedoralOral exposures, p. 2
Ni0.20, 0.066 and 0.022 mg cm-2 equivalent to 5, 1.66 and 0.55% nickel0.20mg/cm2occluded patch, 2 daysPatch testing, p. 2
Ni0.066 mg cm-2 equivalent to 1.66% nickel0.066mg/cm2occluded patchPatch testing, p. 2
Ni0.022 mg cm-2 equivalent to 0.55% nickel0.022mg/cm2occluded patchPatch testing, p. 2
Nidetection limit (<0.12 mg/l)<0.12mg/lserum and urine concentrationNickel analyses, p. 3
Niset at 1/3 of the detection limit (approximately 0.04 mg/l)0.04mg/limputed concentrationNickel analyses, p. 3
Ninickel content in 35 of 60 serum samples … taken before oral exposure was below the detection limit (<0.12 mg/l)35 of 60 below detectioncountserumAnalyses of nickel concentrations, p. 5
Ni46 of 60 urine samples taken before oral exposure was below the detection limit46 of 60 below detectioncounturine, creatinine also measuredAnalyses of nickel concentrations, p. 5
Nifor 6 of 10 nickel content in serum samples taken after exposure was below detection level6 of 10 below detectioncountserumtext, p. 5
Nibelow detection level in 8 of 10 samples from nickel-sensitive volunteers8 of 10 below detectioncounturinetext, p. 5
Ni5 of 10 samples from healthy controls5 of 10 below detectioncounturinetext, p. 5

Methods (brief)

Volunteers were also patch tested with three nickel sulfate hexahydrate loads, 0.20, 0.066, and 0.022 mg/cm2. Oral doses were given in the morning after a 12-hour fast. No dietary nickel control was used. Urine was morning urine, with creatinine measured. Concentrations below detection were replaced by about 0.04 mg/l for analysis.

Evidence fitness

These data support Oral nickel doses administered were 0.3, 1.0, and 4.0 mg nickel as nickel sulfate hexahydrate, plus lactose placebo; Cutaneous reactions in nickel-sensitive volunteers were 4 of 10 at 0.3 mg, 4 of 10 at 1.0 mg, 7 of 10 at 4.0 mg, and 1 of 10 on placebo. No healthy control reacted to 4.0 mg or placebo; Patch concentrations were 0.20, 0.066, and 0.022 mg/cm2, printed as equivalent to 5, 1.66, and 0.55% nickel; Serum and urine nickel before exposure were below <0.12 mg/l in 35 of 60 serum samples and 46 of 60 urine samples. The authors state that after challenge, serum and urine nickel were directly related to dose, without printing the post-dose means.

They do not support Does not measure nickel release from clothing or objects; Does not print numeric post-dose mean serum or urine concentrations; those are only in Figs. 2 and 3; Does not estimate dietary nickel intake in these volunteers; Fasting bolus doses of nickel sulfate are stated by the authors as not directly comparable to nickel in food.

Limitations

Post-dose serum and urine means cannot be read as numbers from the extract of Figs. 2 and 3, so they are not in the ledger. The detection limit is printed in mg/l while the figure axis is labeled µg/l and µg/g creatinine. Literature dietary ranges cited in the introduction (0.1 to 0.5 mg, maximum estimate 0.9 mg, and earlier challenge doses 0.6 to 5.6 mg) are other papers’ numbers and were not ledgered.

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