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., Draize Rabbit Eye Test [DRET]) . The Porcine Corneal Opacity Reversibility Assay (PorCORA), an ex vivo intact corneal tissue culture model, predicts the reversibility of damage by ocular irritants. Inclusion of the damage reversibility endpoint in the PorCORA supplements other alternative test methods for ocular irritation, by assessing induced eye damage and the ability of this damage to reverse (heal) without the use of live animals to distinguish between Globally Harmonised System of Classification and Labelling of Chemicals (GHS) ocular classifications. In this focused study, results of a Bovine Corneal Opacity and Permeability (BCOP) test of a laundry detergent, neat and 10% dilution, (product mixture from S.C. Johnson & Son, Inc. [SCJ]) classified the product into GHS Category 1; however, the BCOP test cannot assess the reversibility of ocular damage. The laundry detergent was evaluated using the PorCORA, where ocular damage induced by the detergent was fully reversed within seven days. Evaluation of the reversibility of ocular damage using the PorCORA in this focused study can add strength to the weight-of-evidence (WoE) analysis approach in ocular hazard assessment. This WoE approach strengthens the argument that the PorCORA can be used to supplement BCOP data, and that this laundry detergent is not an irreversible eye irritant.

Identifying a reference list of respiratory sensitizers for the evaluation of novel approaches to study respiratory sensitization.

The induction of immunological responses that trigger bio-physiological symptoms in the respiratory tract following repeated exposure to a substance, is known as respiratory sensitization. The inducing compound is known as a respiratory sensitizer. While respiratory sensitization by high molecular weight (HMW) materials is recognized and extensively studied, much less information is available regarding low molecular weight (LMW) materials as respiratory sensitizers. Variability of symptoms presented in humans from such exposures, limited availability of (and access to) documented reports, and the absence of standardized and validated test models, hinders the identification of true respiratory sensitizers. This review aims to sort suspected LMW respiratory sensitizers based on available compelling, reasonable, inadequate, or questionable evidence in humans from occupational exposures and use this information to compose a reference list of reported chemical respiratory sensitizers for scientific research purposes. A list of 97 reported respiratory sensitizers was generated from six sources, and 52 LMW organic chemicals were identified, reviewed, and assigned to the four evidence categories. Less than 10 chemicals were confirmed with compelling evidence for induction of respiratory sensitization in humans from occupational exposures. Here, we propose the reference list for developing novel research on respiratory sensitization.

Doing the locomotion: Insights and potential pitfalls associated with using locomotor activity as a readout of the circadian rhythm in larval zebrafish.

BACKGROUND: Zebrafish have been used as a model to study circadian rhythms (CRs) for over 20 years by analyzing various endpoints including locomotor activity. Such studies often utilize high-throughput analysis monitoring activity of larvae placed in well plates numbering >48 wells per plate. Although the CR can be influenced by numerous factors, it is not clear if such effects are permanent. Here, we investigated the variability of CRs of larvae analyzed in different types of well plates and determined the permanency of experimentally-induced aberrations in CRs. NEW METHOD: Utilized the tracking software Ethovision XT to investigate how different well plate sizes influence the CR. Re-tested subjects for recovery from long-term CR disruptions and evaluated CR patterns at the individual level. RESULTS: CR tracking using locomotion as a readout is best in 24 well plates. CR consistency is not maintained in larvae tracked in 48 or 96 well plates. A perturbed CR due to constant light recovered after just 3 days of a normal light/dark cycle. COMPARISON WITH EXISTING METHODS: Unlike other CR locomotor-based assays, our approach allowed for a medium-throughput analysis of individual CRs, minimized variability and allowed for the re-evaluation of larval CRs 4-5 days later. CONCLUSIONS: This medium-throughput locomotor CR analysis allows for a standardized, less variable approach whereby larvae can be re-tested to identify potential long-term changes after experimental manipulations. Long-term behavioral experiments in 48 or 96 well plates may impart stress on the larvae due to space constraints which could impact nervous system function and/or behavior.