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Further investigations are recommended on the prevalence of isothiazolinone-induced allergic contact dermatitis and the allergenic potential of co-polymers/cross-polymers.

A literature study was performed to evaluate dose-response relationships and no-effect levels for sensitization and elicitation in skin- and respiratory allergy. With respect to the skin, dose-response relationships and no-effect levels were found for both intradermal and topical induction, as well as for intradermal and topical elicitation of allergenic responses in epidemiological, clinical, and animal studies. Skin damage or irritation may result in a significant reduction of the no-effect level for a specific compound. With respect to the respiratory tract, dose-response relationships and no-effect levels for induction were found in several human as well as animal studies. Although dose-response relationships for elicitation were found in some epidemiological studies, concentration-response relationships were present only in a limited number of animal studies. Reported results suggest that especially relatively high peak concentrations can induce sensitization, and that prevention of such concentrations will prevent workers from developing respiratory allergy. Moreover, induction of skin sensitization may result in subsequent heightened respiratory responsiveness following inhalation exposure. The threshold concentration for the elicitation of allergic airway reactions in sensitized subjects is generally lower than the threshold to induce sensitization. Therefore, it is important to consider the low threshold levels for elicitation for recommendation of health-based occupational exposure limits, and to avoid high peak concentrations. Notwithstanding the observation of dose-response relationships and no-effect levels, due to a number of uncertainties, no definite conclusions can be drawn about absolute threshold values for allergens with respect to sensitization of and elicitation reactions in the skin and respiratory tract. Most predictive tests are generally meant to detect the potential of a chemical to induce skin and/or respiratory allergy at relatively high doses. Consequently, these tests do not provide information of dose-response relationships at lower doses such as found in, for example, occupational situations. In addition, the observed dose-response relationships and threshold values have been obtained by a wide variety of test methods using different techniques, such as intradermal exposure versus topical or inhalation exposure at the workplace, or using different endpoints, which all appear important for the outcome of the test. Therefore, especially with regard to respiratory allergy, standardized and validated dose-response test methods are urgently required in order to be able to recommend safe exposure levels for allergens at the workplace.

Exposure to certain drugs and environmental chemicals can provoke the onset of autoimmune disease in susceptible individuals by releasing (self) epitopes for which tolerance has not been established, while simultaneously providing the necessary adjuvant activity. The resulting response type is influenced by the genotype of exposed individuals and relates to susceptibility to the adverse immune effects of the chemicals. Here, we assessed the modulatory role of the chemical compounds themselves. A single injection of streptozotocin (STZ) increased the number of CD8+ cells, macrophages, apoptotic cells, and IFN-gamma-producing T helper and T cytotoxic cells, whereas the number of CD4+ cells and B cells was reduced in the draining lymph node. Coinjection with the reporter antigen TNP-OVA resulted in primary and secondary production of TNP-specific antibodies that were predominantly of IgG2a and IgG2b isotype, whereas STZ did not enhance priming for delayed-type hypersensitivity (DTH) responses to TNP-OVA. Injection of HgCl2 on the other hand, reduced the number of IFN-gamma-producing cells, induced accumulation of B cells and CD4+ and CD8+ T cells, enhanced IgG1 and IgE production to TNP-OVA, and primed for secondary IgG1 and IgE production as well as for DTH reactions. Together these results indicate that a single injection of STZ stimulates type-1 responses, whereas HgCl2 enhanced mixed type-1 and -2 responses in BALB/c mice. These response types match the (auto)immune effects elicited to unknown (auto)antigens following multiple injections of these chemicals.