Effect of simultaneous exposure to mixture of two skin sensitizers on skin sensitization response in guinea pigs and mice

Abstract

Skin sensitization resulting in allergic contact dermatitis is a common occupational health issue. In this study, the effect of mixing two skin sensitizers on the skin sensitization response was investigated. Skin sensitizers are generally classified into T helper type 1 (Th1) or T helper type 2 (Th2), depending on the induced cytokine profile. Dinitrochlorobenzene (DNCB) and oxazolone (Oxa) are Th1 skin sensitizers and phthalic anhydride (PA) and toluene diisocyanate (TDI) are Th2 skin sensitizers. We investigated the effect on skin sensitization response to mixtures of three pairs of these sensitizers: DNCB and Oxa, DNCB and PA, and PA and TDI, using guinea pig maximization test and mouse ear swelling test. In guinea pigs sensitized with the mixture of DNCB and Oxa or PA and TDI, there were changes of skin sensitization response to DNCB and Oxa, and that to PA. On the other hand, there was no mixture effect in guinea pigs sensitized with the mixture of DNCB and PA. The skin sensitization responses were decreased in mice sensitized with the mixtures of DNCB and Oxa or PA and TDI, whereas the mixture effect was not observed in mice sensitized with the mixture of DNCB and PA. The present findings revealed that mixture effect on the skin sensitization response was observed after simultaneous exposure to two skin sensitizers, and the effect was determined by combinations of mixed skin sensitizers.

Activation of aryl hydrocarbon receptor by benzo[a]pyrene increases interleukin 33 expression and eosinophil infiltration in a mouse model of allergic airway inflammation

“…Our present study also highlighted the effect of BaP exposure in a Th2‐driven respiratory disease model, which is generated by repetitive sensitization and challenging with a strong Th2‐type hapten TDI in female BALB/c mice. TDI is recognized as a Th2‐dependent hapten and TDI‐induced animal models have a similar effect as human atopic dermatitis and allergic asthma (Morimoto et al, 2014; Park et al, 2018). In actuality, a mouse model of TDI‐induced allergy is a high‐integrity mouse model, which has been widely used for detection of immunotoxicologic effects of environmental chemicals including estrogen disruptors and BaP (Tajiki‐Nishino et al, 2018b; Tajima et al, 2019; Watanabe et al, 2018; Watanabe et al, 2019).…”

“…TDI is recognized as a Th2-dependent hapten and TDI-induced animal models have a similar effect as human atopic dermatitis and allergic asthma (Morimoto et al, 2014;Park et al, 2018). In actuality, a mouse model of TDI-induced allergy is a high-integrity mouse model, which has been widely used for detection of immunotoxicologic effects of environmental chemicals including estrogen disruptors and BaP (Tajiki-Nishino et al, 2018b;Tajima et al, 2019;Watanabe et al, 2018;Watanabe et al, 2019).…”

Acidic conditions induce the suppression of CD86 and CD54 expression in THP-1 cells

“…In general, consumers are rarely exposed to a single isolated allergen, but are typically exposed to mixtures of allergens (Uter et al, 2013(Uter et al, , 2014. Accordingly, to accurately evaluate skin sensitization potential, additional studies are needed to examine mixtures containing multiple test chemicals (Bonefeld et al, 2017;Kienhuis et al, 2015;Lourenço et al, 2015;Morimoto et al, 2014). Moreover, further studies are required to evaluate and improve consumer safety and to clarify the mechanism by which CD86/CD54 suppression was induced by an acidic pH.…”

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“…The challenge phase begins upon elicitation by hapten and results in the clinical symptoms. Skin sensitizers are generally classified into T hepler type 1(Th1) or T hepler type 2 (Th2) depending on the induced cytokine profile [13]. On the other hand, exposure to volatile solvents like toluene, may be caused by an occupational exposure in industrial settings or a volatile substance abuse [14].…”

“…On the other hand, exposure to volatile solvents like toluene, may be caused by an occupational exposure in industrial settings or a volatile substance abuse [14]. Toluene diisocyanate (TDI) is a very toxic volatile substance that is an aromatic hydrocarbone [15], and it is also a Th2 skin sensitizer [13] and is a weak skin irritant [16]. There are many report about the effect of chemicals on skin sensitization response [17,18].…”