Irritation Potential Of Chemicals Research Articles

Comparative analysis of respiratory, skin and eye irritation potential of chemicals using Japanese GHS classification

Comparative analysis of respiratory, skin and eye irritation potential of chemicals using Japanese GHS classification

A new alternative method to the Draize eye test for the assessment of the eye irritation potential of chemicals by using HCE-T cell

A new alternative method to the Draize eye test for the assessment of the eye irritation potential of chemicals by using HCE-T cell

Quantitative structure–property relationships modeling of skin irritation

Interest in developing procedures for estimating skin irritation potential of chemicals has been increasing as a result of concerns regarding animal welfare and costs involved in experimental irritation studies. In response to these concerns, a number of expert systems and quantitative structure-activity relationship (QSAR) models have been proposed for predicting the skin irritation potential of compounds. However, these models require as input independent estimates of several physiochemical properties. Hence, to predict skin irritation potential using these models often requires additional models capable of estimating the physiochemical properties of diverse structures; a requirement that most literature QSARs fail to meet. In the work reported here, we developed a skin irritation QSPR model based on rabbit Draize test data for 186 compounds, which included chemicals from diverse molecular classes. The effectiveness of using a combination of traditional, functional group and structural descriptors has been studied. Our non-linear QSPR model is capable of predicting the skin irritation potential of chemical compounds with an R2 of 0.78. Further, the final set of descriptors used to model skin irritation was analyzed to elucidate the effects of molecular size, reactivity and skin penetration on skin irritation.

Pre-validation of organotypic EpiVaginal™ tissue model to screen irritation potential of chemicals

Pre-validation of organotypic EpiVaginal™ tissue model to screen irritation potential of chemicals

Refinement of the Slug Mucosal Irritation test as an alternative screening test for eye irritation

The objective of this study was to limit the test procedure time of the Slug Mucosal Irritation test to one day and to determine whether it is a relevant and reliable method to predict the eye irritation potential of chemicals. The irritation potential of several eye reference chemicals can be estimated by the amount of mucus produced when tested at a 1% concentration (60 min). Since some in vivo irritating chemicals did not influence this endpoint the effect of increasing concentrations on membrane damage was investigated. This study revealed that when tested at a 3.5% concentration (60 min) the underestimated chemicals induced an increased protein and/or enzyme release. A two-step classification prediction model was developed that classified the chemicals first by the amount of mucus produced (1%, 60 min). Chemicals that did not affect this endpoint were classified based on the membrane damage induced by a second treatment (3.5%, 60 min). The results were compared with the corresponding EU classification (NI, R36 and R41) and 71% of the chemicals were correctly classified with a specificity and sensitivity of 75% and 94%, respectively. Repeated testing of the chemicals revealed a good intra-laboratory reproducibility. The test seems to be a promising method for screening the eye irritating potential of chemicals.

Interleukin-1α and Interleukin-8 Release by Human Keratinocyte Cell Culture Treated with Surfactants

The effects of four cosmetic surfactants on interleukin (IL)-1α and IL-8 release from human keratinocytes were studied to investigate the feasibility of using these effects for the prediction of the irritation potential of chemicals. After exposure of cells to surfactants, the amounts of IL-1α and IL-8 released into culture medium were measured by ELISA. Cytotoxicity was evaluated by using the neutral red uptake (NRU) cytotoxicity assay. Cytokine release was increased 7–15 times by sodium lauryl sulphate (SLS), laurtrimonium chloride, cocamidopropyl betaine (CPB) and Oleth-5 at cytotoxic concentrations. IL-8 release was increased 3–4 times by SLS, CPB and Oleth-5 at subcytotoxic concentrations. After exposure to SLS, IL-1α was released within 1 hour, suggesting that IL-1α release is associated with membrane damage, whereas IL-8 release continued for 24 hours, suggesting that IL-8 was produced within the cells. Cytotoxicity tests and IL-8 release assays were also performed on seven other surfactants. The results show that moderate irritants CPB and PEG-4 dioleate, which have weak cytotoxic effects, significantly increased IL-8 release from human keratinocytes. It is suggested that measurement of IL-8 release is useful for predicting the irritation potential of chemicals which cannot be detected by using the NRU cytotoxicity assay.

Surfactant Cytotoxicity Potential Evaluated with Primary Cultures of Ocular Tissues: a Method for the Culture of Rabbit Conjunctival Epithelial Cells and Initial Cytotoxicity Studies

Rabbit conjunctiva, cornea, and iris have been used to evaluate and rank the ocular irritation potential of chemicals in the Draize eye irritancy test by subjective criteria. In order to rank the irritancy potential of chemicals objectively and biochemically, a primary culture method for rabbit conjunctival epithelial cells has been developed in our laboratory as a potential in vitro method for ocular toxicity testing of xenobiotics. Conjunctival epithelial cells were dispersed by Dispase II, followed by trypsin treatment. Cells were cultured in serum-free medium of 1:1 ratio of Dulbecco's modified Eagle's medium (DMEM) and F-12 nutrient mixture plus various concentrations of growth factors. At a plating density of 85,000 cells/cm2, cells grew to confluency in 3-4 days. Conjunctival cells showed a positive anti-keratin antibody stain which demonstrated their epithelial nature. These cells also showed positive periodic acid-Schiff (PAS) staining which is consistent with their goblet cell-containing and muc...

In vitro Methods for the Assessment of Primary Local Effects of Topically Applied Preparations

Three 'alternative' methods for the screening of the primary irritation potentials of topically applied preparations and raw materials are presented as a test battery and their in vitro endpoints are compared with in vivo data. The first method is the intermediate test on the chorioallantoic membrane of hens' fertilized eggs, which is generally proposed for the prediction of the irritation potential of chemicals. Relevant test parameters, such as the time-dependent appearance of hemorrhages, vascular lysis and coagulation, are used to classify the test substances. Secondly, cytotoxicity tests with Balb/c 3T3 fibroblasts are used to characterize the influence of test materials on cellular homeostasis and viability, which is quantified by the dose-dependent uptake of Neutral red. As a second parameter changes in the cellular protein level can be easily measured by subsequent staining with Kenacid blue. Finally, the third approach to in vitro evaluation is presented in the form of the red blood cell assay, a rapid photometric assay which permits distinguishing basically between damage to the membrane and to proteins as endpoints which correlate with lesions observed on the conjunctiva, iris and cornea in the eye and the acute inflammatory responses evoked during epicutaneous irritancy testing. Changes in the optical behavior of oxyhemoglobin are used as the inherent indicator for monitoring both endpoints and their interrelations. These methods are proposed and can be used advantageously for testing newly developed topical preparations and their ingredients in view of their local irritation potential without further use of animal testing. Moreover, they can also be used for screening chemicals.