Irritancy and allergic responses induced by topical application of ortho-phthalaldehyde.

Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505, USA.
Toxicological Sciences (Impact Factor: 4.48). 02/2010; 115(2):435-43. DOI: 10.1093/toxsci/kfq054
Source: PubMed

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.

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    ABSTRACT: Two independent sampling and analytical methods for ortho-phthalaldehyde (OPA) in air have been developed, evaluated and compared: (1) a reagent-coated solid sorbent HPLC-UV method and (2) an impinger-fluorescence method. In the first method, air sampling is conducted at 1.0 L min−1 with a sampler containing 350 mg of silica gel coated with 1 mg of acidified 2,4-dinitrophenylhydrazine (DNPH). After sampling, excess DNPH in ethyl acetate is added to the sampler prior to storage for 68 hours. The OPA-DNPH derivative is eluted with 4.0 mL of dimethyl sulfoxide (DMSO) for measurement by HPLC with a UV detector set at 385 nm. The estimated detection limit is 0.016 μg per sample or 0.067 μg m−3 (0.012 ppb) for a 240 L air sample. Recoveries of vapor spikes at levels of 1.2 to 6.2 μg were 96 to 101%. Recoveries of spikes as mixtures of vapor and condensation aerosols were 97 to 100%. In the second method, air sampling is conducted at 1.0 L min−1 with a midget impinger containing 10 mL of DMSO solution containing N-acetyl-L-cysteine and ethylenediamine. The fluorescence reading is taken 80 min after the completion of air sampling. Since the time of taking the fluorescence reading is critical, the reading is taken with a portable fluorometer. The estimated detection limit is 0.024 μg per sample or 0.1 μg m−3 (0.018 ppb) for a 240 L air sample. Recoveries of OPA vapor spikes at levels of 1.4 to 5.0 μg per sample were 97 to 105%. Recoveries of spikes as mixtures of vapors and condensation aerosols were 95 to 99%. The collection efficiency for a mixture of vapor and condensation aerosol was 99.4%. The two methods were compared side-by-side in a generation system constructed for producing controlled atmospheres of OPA vapor in air. Average air concentrations of OPA vapor found by both methods agreed within ±10%.
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    ABSTRACT: There are a large number of workers in the United States, spanning a variety of occupational industries and sectors, who are potentially exposed to chemicals that can be absorbed through the skin. Occupational skin exposures can result in numerous diseases that can adversely affect an individual's health and capacity to perform at work. In general, there are three types of chemical-skin interactions of concern: direct skin effects, immune-mediated skin effects, and systemic effects. While hundreds of chemicals (metals, epoxy and acrylic resins, rubber additives, and chemical intermediates) present in virtually every industry have been identified to cause direct and immune-mediated effects such as contact dermatitis or urticaria, less is known about the number and types of chemicals contributing to systemic effects. In an attempt to raise awareness, skin notation assignments communicate the potential for dermal absorption; however, there is a need for standardization among agencies to communicate an accurate description of occupational hazards. Studies have suggested that exposure to complex mixtures, excessive hand washing, use of hand sanitizers, high frequency of wet work, and environmental or other factors may enhance penetration and stimulate other biological responses altering the outcomes of dermal chemical exposure. Understanding the hazards of dermal exposure is essential for the proper implementation of protective measures to ensure worker safety and health.
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