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Recently, we showed that the addition of physiological concentrations of ascorbic acid, a tear antioxidant, to the OptiSafe™ macromolecular eye irritation test reduced the false-positive (FP) rate for chemicals that had reactive chemistries, leading to the formation of reactive oxygen species (ROS) and molecular crosslinking. The purpose of the current study was to 1) increase the number of chemicals tested to comprehensibly determine whether the antioxidant-associated reduction in OD is specific to FP chemicals associated with ROS chemistries and 2) determine whether the addition of antioxidants interferes with the detection of true positive (TP) and true negative (TN) ocular irritants. We report that when ascorbic acid is added to the test reagents, retesting of FP chemicals with reactive chemistries show significantly reduced OD values (P < 0.05). Importantly, ascorbic acid had no significant effect on the OD values of TP or TN chemicals regardless of chemical reactivity. These findings suggest that supplementation of ascorbic acid in alternative ocular irritation tests may help improve the detection of TN for those commonly misclassified reactive chemicals.

Quantification of eye irritancy has been a problem for both the consumer product industry and ophthalmic researchers because of the need to predict the toxic potential of preparations that may come into contact with the ocular surface. The Draize rabbit eye test has been used for 60 years in attempts to predict human ocular irritancy based on topical instillation of the potential irritant and subjective scoring of ocular inflammation by direct visualization of the rabbit eye. The inadequacies of the Draize test have led to efforts in several laboratories to develop alternatives.

[Purpose] The aim of this study was to find new biocompatible surfactants and mixtures with low ocular irritant action for application in pharmaceutical formulations and to establish a relationship between their structure and their potential ocular irritant activity., [Methods] An alternative method to the Draize in vivo test, based on the adverse effects of surfactants on the cytoplasmic membrane of red blood cell, was used to evaluate the potential ocular irritation of the surfactants., [Results] It was found that the hemolytic activity of arginine-based gemini surfactants increased with the aliphatic alkyl chain lengths of the hydrophobic tail. The addition of the surfactant with an alkyl chain length of 10 carbon atoms to cocoamidopropilbetaina (TB), decylglucoside (APG), and Nagr-lauroyl-arginine ethyl ester (LAE) increases the hemolytic activity moderately for the mixtures with TB and LAE (1.1- and 1.5-fold, respectively) and strongly for APG (fivefold)., [Conclusions] The new arginine-based gemini surfactants constitute a suitable alternative to commercial surfactants because of their natural origins, which make them biocompatible and renewable products. Based on their hemolytic activity as an alternative to the Draize test, these new arginine-based gemini surfactants and their mixtures can be classified as mild irritants. This fact constitutes an advantage, especially for pharmaceutical and cosmetic applications.

[ES] El desarrollo de nuevos tensioactivos con pocos efectos tóxicos, constituye uno de los importantes objeti vos de la síntesis orgánica. Entre los tensioactivos, los deri vados de aminoácidos representan un grupo potencialmente poco tóxico. En este trabajo hemos estudiado la acción irritativa dérmica y ocular y el posible efecto tóxico tras administración intravenosa en ratones, de una serie de nuevos tensioactivos lipopeptídicos derivados de Usina, con longitudes de cadena diferente para conocer la relación estructura/toxicidad y su posible aplicación en la Industria Farmacéutica y/o Cosmética. Todos los productos estudiados resultaron no irritantes a las dosis ensayadas y fueron menos tóxicos que otros ten sioactivos conocidos., [EN] Toxicity of new surfactants. The development of new surfactants with few toxic effects is one of the important objectives of the organic synthesis. Among the surfactants, those derived from aminoacid represent a potential not much toxic group. In the present work we have studied the dermic and ocular irritative action and the toxic effect, after intravenous injection in mouse of a serie of new surfactants derived from lysine with different chain length in order to know the ratio structure/toxicity and their potential aplication in the Pharmaceutical and/or Cosmetic fields. All the products investigated were not irritant at the dose tested and were less toxic than other very used surfactants.