Elicitation threshold of cobalt chloride: analysis of patch test dose-response studies.

BACKGROUND: Cobalt is a strong skin sensitizer (grade 5 of 5 in the guinea-pig maximization test) that is used in various industrial and consumer applications. To prevent sensitization to cobalt and elicitation of allergic cobalt dermatitis, information about the elicitation threshold level of cobalt is important. OBJECTIVE: To identify the dermatitis elicitation threshold levels in cobalt-allergic individuals. MATERIALS AND METHODS: Published patch test dose-response studies were reviewed to determine the elicitation dose (ED) levels in dermatitis patients with a previous positive patch test reaction to cobalt. A logistic dose-response model was applied to data collected from the published literature to estimate ED values. The 95% confidence interval (CI) for the ratio of mean doses that can elicit a reaction in 10% (ED(10)) of a population was calculated with Fieller's method. RESULTS: On the basis of five included studies, the ED10 values of aqueous cobalt chloride ranged between 0.0663 and 1.95 µg cobalt/cm(2), corresponding to 30.8-259 ppm. CONCLUSIONS: Our analysis provides an overview of the doses of cobalt that are required to elicit allergic cobalt contactdermatitis in sensitized individuals, and thereby the basis for future prevention of cobalt allergy.

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.