Irritancy and Allergic Responses Induced by Topical Application of ortho-Phthalaldehyde

Abstract

Although ortho-phthalaldehyde (OPA) has been suggested as an alternative to glutaraldehyde for the sterilization and disinfection of hospital equipment, the toxicity has not been thoroughly investigated. The purpose of these studies was to evaluate the irritancy and sensitization potential of OPA. The EpiDerm Skin Irritation Test was used to evaluate in vitro irritancy potential of OPA and glutaraldehyde. Treatment with 0.4125 and 0.55% OPA induced irritation, while glutaraldehyde exposure at these concentrations did not. Consistent with the in vitro results, OPA induced irritancy, evaluated by ear swelling, when mice were treated with 0.75%. Initial evaluation of the sensitization potential was conducted using the local lymph node assay at concentrations ranging from 0.005 to 0.75%. A concentration-dependent increase in lymphocyte proliferation was observed with a calculated EC3 value of 0.051% compared to that of 0.089%, previously determined for glutaraldehyde. Immunoglobulin (Ig) E-inducing potential was evaluated by phenotypic analysis of draining lymph node (DLN) cells and measurement of total and specific serum IgE levels. The 0.1 and 0.75% exposed groups yielded significant increases in the IgE+B220+ cell population in the lymph nodes while the 0.75% treated group demonstrated significant increases in total IgE, OPA-specific IgE, and OPA-specific IgG(1). In addition, significant increases in interleukin-4 messenger RNA and protein expression in the DLNs were observed in OPA-treated groups. The results demonstrate the dermal irritancy and allergic potential of OPA and raise concern about the proposed/intended use of OPA as a safe alternative to glutaraldehyde.

Expression kinetics of miRNA involved in dermal toluene 2,4-diisocyanate sensitization

“…This strain was selected because these mice are good IgE producers and have historically been used in the laboratory to evaluate chemical sensitization (Anderson et al, 2010). Mice were housed at a maximum of five per cage in ventilated plastic shoebox cages with hardwood chip bedding, NIH-31 modified 6% irradiated rodent diet (Harlan Teklad), and filtered tap water (ad libitum).…”

“…Olive oil has poly-ols and therefore the stability of free diisocyanate in olive oil would be a concern. This vehicle control has also historically been used in our laboratory to evaluate chemical sensitization (Anderson et al, 2010;Franko et al, 2012).…”

“…Chemical sensitization was confirmed by expression of allergic cytokines (IL-4, IL-5, IL-13, and IFNg) protein expression and total serum IgE using methods previously described (Anderson et al, 2010;Franko et al, 2012).…”

Health hazard evaluation report: evaluation of ortho-phthalaldehyde in eight healthcare facilities.

“…Elicitation of irritant and allergic reactions in mice has been reported [Anderson et al 2010;Morinaga et al 2010]. More recently, other investigators have found that inhalation of OPA vapors in mice can trigger both respiratory and systemic sensitization.…”

“…We were not able from our PST and OPA-specific IgE results to determine if either method was an accurate measure of OPA sensitization. A laboratory study in mice showed that dermal OPA exposure resulted in dermal irritation and potential sensitization [Anderson 2010]. Topical application of OPA to mice also resulted in significant increases in total IgE, OPA-specific IgE, and OPA-specific IgG 1 [Anderson et al 2010].…”