Can exposure limitations for well-known contact allergens be simplified? An analysis of dose-response patch test data.

BACKGROUND: Allergic contact dermatitis is triggered by chemicals in the environment. Primary prevention is aimed at minimizing the risk of induction, whereas secondary and tertiary prevention are aimed at reducing elicitation. OBJECTIVES: To identify the elicitation doses that will elicit an allergic reaction in 10% of allergic individuals under patch test conditions (ED(10) patch test) for different allergens, and to compare the results with those for different allergens and with animal data indicating sensitizing potency from the literature. MATERIALS AND METHODS: The literature was searched for patch test elicitation studies that fulfilled six selected criteria. The elicitation doses were calculated, and fitted dose-response curves were drawn. RESULTS: Sixteen studies with eight different allergens-methylchloroisothiazolinone/ methylisothiazolinone, formaldehyde, nickel, cobalt, chromium, isoeugenol, hydroxyiso hexyl 3-cyclohexene carboxaldehyde, and methyldibromo glutaronitrile-were selected. The median ED(10) value was 0.835 µg/cm(2). The ED(10) patch test values were all within a factor of 7 from the lowest to the highest value, leaving out three outliers. No obvious patterns between the sensitization and elicitation doses for the allergens were found. CONCLUSIONS: We found a rather small variation in the ED(10) patch test between the allergens, and no clear relationship between induction potency and elicitation threshold of a range of allergens. This knowledge may stimulate thoughts on introducing a generic approach for limitations in exposure to well-known allergens.

The dose-response relationship between the patch test and ROAT and the potential use for regulatory purposes.

BACKGROUND: Allergic contact dermatitis is common and can be prevented. The relationship between thresholds for patch tests and the repeated open application test (ROAT) is unclear. It would be desirable if patch test and ROAT data from already sensitized individuals could be used in prevention. OBJECTIVES: The aim was to develop an equation that could predict the response to an allergen in a ROAT based on the dose-response curve derived by patch testing. MATERIALS/METHODS: Results from two human experimental elicitation studies with non-volatile allergens, nickel and the preservative methyldibromo glutaronitrile (MDBGN), were analysed by logistic dose-response statistics. The relation for volatile compounds was investigated using the results from experiments with the fragrance chemicals hydroxyisohexyl 3-cyclohexene carboxaldehyde and isoeugenol. RESULTS: For non-volatile compounds, the outcome of a ROAT can be estimated from the patch test by: ED(xx)(ROAT) = 0.0296 ED(xx)(patch test). For volatile compounds, the equation predicts that the response in the ROAT is more severe than the patch test response, but it overestimates the response. CONCLUSIONS: This equation may be used for non-volatile compounds other than nickel and MDBGN, after further validation. The relationship between the patch test and the ROAT can be used for prevention, to set safe levels of allergen exposure based on patch test data.

Dose per unit area - a study of elicitation of nickel allergy.

BACKGROUND: Experimental sensitization depends upon the amount of allergen per unit skin area and is largely independent of the area size. OBJECTIVES: This study aimed at testing if this also applies for elicitation of nickel allergy. PATIENTS/METHODS: 20 nickel allergic individuals were tested with a patch test and a repeated open application test (ROAT). Nickel was applied on small and large areas. The varying parameters were area, total dose and dose per unit area. RESULTS: In the patch test, at a low concentration [15 microg nickel (microg Ni)/cm(2)], there were significantly higher scores on the large area with the same dose per area as the small area. At higher concentrations of nickel, no significant differences were found. In the ROAT at low concentration (6.64 microg Ni/cm(2)), it was found that the latency period until a reaction appeared was significantly shorter on the large area compared to the small area. It was also found that the ROAT threshold (per application) was lower than the patch test threshold. CONCLUSION: For elicitation of nickel allergy, the size of the exposed area and therefore the total amount of applied nickel, influence the elicitation reaction at some concentrations, even though the same dose per unit area is applied.

Experimental nickel elicitation thresholds--a review focusing on occluded nickel exposure.

Nickel (Ni) is the most frequent cause of contact allergy among the female population. This makes it interesting to examine thresholds for elicitation under different conditions. Even though Ni exposure may be open, occluded, penetrating or oral, most dose-response studies in the literature concern single occluded application. The aims of this study were to assess thresholds of response by making a statistical analysis of available dose-response studies with single occluded exposure and comparing the results to thresholds from other modes of exposure. 8 occluded Ni dose-response studies were selected based on statistical considerations. The statistical analysis showed that 5% of a sensitized population react to 0.44 microg Ni/cm2 and 10% react to 1.04 microg Ni/cm2. In another study with a single open application, 7.8% of sensitized persons responded to a dose x6 higher than the dose to which 10% reacted in occluded exposure. When combining the exposure to Ni with an irritant, divagating results were found, although the literature shows evidence of an augmented response when combining exposure to an allergen and an irritant. The thresholds of penetrating exposure were found to be lower than the thresholds of single occluded exposure. Comparisons of different kind of exposures across studies are difficult, because of differences in the studies, although a comparison could be made by a study that compares the different exposures within the same individuals at the same time.