Ocular irritation reversibility assessment of a laundry detergent using the Porcine Corneal Opacity Reversibility Assay (PorCORA): a focused study.

Consumer product manufacturers utilise a spectrum of alternative ocular irritation assays, as these tests do not require the use of live animals. Despite their usefulness, no regulatory-accepted assay assesses the reversibility of ocular damage, a key criterion of GHS ocular classification, like the rabbit eye test (i.e.

Validation of the OptiSafe™ eye irritation test.

Purpose: OptiSafe is an test method that identifies potential eye irritants based on macromolecular damage following test chemical exposure. The OptiSafe protocol includes a prescreen assessment that identifies test chemicals that are outside the applicability domain of the test method and thus determines the optimal procedure. We assessed the usefulness and limitations of the OptiSafe test method for identifying chemicals not requiring classification for ocular irritation (i.

Guidance on assessing the methodological and reporting quality of toxicologically relevant studies: A scoping review.

Assessments of methodological and reporting quality are critical to adequately judging the credibility of a study's conclusions and to gauging its potential reproducibility. To aid those seeking to assess the methodological or reporting quality of studies relevant to toxicology, we conducted a scoping review of the available guidance with respect to four types of studies: in vivo and in vitro, (quantitative) structure-activity relationships ([Q]SARs), physico-chemical, and human observational studies. Our aims were to identify the available guidance in this diverse literature, briefly summarize each document, and distill the common elements of these documents for each study type.

An epidermal equivalent assay for identification and ranking potency of contact sensitizers.

The purpose of this study was to explore the possibility of combining the epidermal equivalent (EE) potency assay with the assay which assesses release of interleukin-18 (IL-18) to provide a single test for identification and classification of skin sensitizing chemicals, including chemicals of low water solubility or stability. A protocol was developed using different 3D-epidermal models including in house VUMC model, epiCS® (previously EST1000™), MatTek EpiDerm™ and SkinEthic™ RHE and also the impact of different vehicles (acetone:olive oil 4:1, 1% DMSO, ethanol, water) was investigated. Following topical exposure for 24h to 17 contact allergens and 13 non-sensitizers a robust increase in IL-18 release was observed only after exposure to contact allergens.

Porcine Corneal Ocular Reversibility Assay (PorCORA) predicts ocular damage and recovery for global regulatory agency hazard categories.

In this study, we examined the capacity of the Porcine Corneal Ocular Reversibility Assay (PorCORA) to classify the reversibility of ocular effects for 32 test compounds (20 reversible, 12 irreversible) from various chemical classes. PorCORA predicted 28 of 32 compounds correctly when compared to historical rabbit eye test data. The correlation coefficient for PorCORA versus historical rabbit test data was 0.

Novel cultured porcine corneal irritancy assay with reversibility endpoint.

Several alternative assays exist to assess ocular irritancy without the use of live animals. However, these assays cannot address ocular injury reversibility. Reversibility is an issue critical to regulatory authorities and manufactures of commercial products, as ocular irritation caused by misuse or accidental exposure to a product may cause irreversible eye damage.

28-day repeated dose oral toxicity of recombinant human holo-lactoferrin in rats.

Recombinant human holo-lactoferrin (holo-rhLF) was orally administered, via gavage, to Wistar rats at 1000, 500 and 100mg/kgbw/day for 28 days. The test article, holo-rhLF, was expressed in rice grain, extracted, purified and saturated with iron. During the 28-day period, animals were examined for evidence of toxicity.

28-Day repeated dose oral toxicity of recombinant human apo-lactoferrin or recombinant human lysozyme in rats.

Lactoferrin and lysozyme are important proteins of the human innate immune system. These proteins are found in breast milk and have been associated with improved infant health. Recombinant human apo-lactoferrin (apo-rhLF), 1800 and 180mg/kg bw/day, and recombinant human lysozyme (rhLZ), 360 and 36mg/kg bw/day, were orally administered to Wistar rats for 28 days.

Acetaminophen-induced proliferation of breast cancer cells involves estrogen receptors.

Previous studies have shown that acetaminophen, a common analgesic/antipyretic, induces proliferation of cultured breast cancer cells containing both estrogen and progesterone receptors (ER+/PR+). The main objective of this study was to evaluate the involvement of ERs in this effect. First, the effects of therapeutic acetaminophen concentrations were compared in breast cancer cells with high ERs and in T47Dco cells with lower ERs, to determine if acetaminophen-induced proliferation depends on ER levels.

Suppression of anti-microtubule agent-induced apoptosis by nitric oxide: possible mechanism of a new drug resistance.

The propensity of a cell to undergo apoptosis has been proposed to be a determinant of sensitivity to anti-microtubule agents. The anti-microtubule agents vincristine and paclitaxel induce key features of apoptosis, such as intranucleosomal DNA fragmentation and changes in nuclear morphology in the human neuroblastoma cell line, NB-39-nu. Nitric oxide (NO) generated from NO-releasing drugs prevented anti-microtubule agent-induced apoptosis in this cell line.

Role of nitric oxide in acetaminophen-induced hepatotoxicity in the rat.

Acetaminophen is a mild analgesic and antipyretic agent known to cause centrilobular hepatic necrosis at toxic doses. Although this may be due to a direct interaction of reactive acetaminophen metabolites with hepatocyte proteins, recent studies have suggested that cytotoxic mediators produced by parenchymal and nonparenchymal cells also contribute to the pathophysiological process. Nitric oxide is a highly reactive oxidant produced in the liver in response to inflammatory mediators.

Arginine metabolism in keratinocytes and macrophages during nitric oxide biosynthesis: multiple modes of action of nitric oxide synthase inhibitors.

Nitric oxide is an important cellular mediator produced in keratinocytes and macrophages from arginine by the enzyme nitric oxide synthase during inflammatory reactions in the skin. We found that gamma-interferon stimulated nitric oxide production and the expression of inducible nitric oxide synthase in both cell types. However, macrophages produced more nitric oxide and nitric oxide synthase protein, and at earlier times than keratinocytes.

5-Fluorouracil suppresses nitric oxide biosynthesis in colon carcinoma cells.

Nitric oxide is an important cellular mediator that plays a role in regulating cellular proliferation of both normal and tumor cells. In the present study, we characterized nitric oxide production by the human colon adenocarcinoma cell line DLD-1 and examined the effects of 5-fluorouracil (5-FUra), an antimetabolite effective against colon tumors, on nitric oxide production. IFN-gamma was found to be a potent inducer of nitric oxide production in DLD-1 cells.