Non-animal Replacements for Acute Toxicity Testing.

Current approaches to predicting adverse effects in humans from acute toxic exposure to cosmetic ingredients still heavily necessitate the use of animals under EU legislation, particularly in the context of the REACH system, when cosmetic ingredients are also destined for use in other industries. These include the LD50 test, the Up-and-Down Procedure and the Fixed Dose Procedure, which are regarded as having notable scientific deficiencies and low transferability to humans. By expanding on previous in vitro tests, such as the animal cell-based 3T3 Neutral Red Uptake (NRU) assay, this project aims to develop a truly animal-free predictive test for the acute toxicity of cosmetic ingredients in humans, by using human-derived cells and a prediction model that does not rely on animal data. The project, funded by Innovate UK, will incorporate the NRU assay with human dermal fibroblasts in animal product-free culture, to generate an in vitro protocol that can be validated as an accepted replacement for the currently available in vivo tests. To date, the project has successfully completed an assessment of the robustness and reproducibility of the method, by using sodium lauryl sulphate (SLS) as a positive control, and displaying analogous results to those of the original studies with mouse 3T3 cells. Currently, the testing of five known ingredients from key groups (a surfactant, a preservative, a fragrance, a colour and an emulsifier) is under way. The testing consists of initial range-finding runs followed by three valid runs of a main experiment with the appropriate concentration ranges, to generate IC50 values. Expanded blind trials of 20 ingredients will follow. Early results indicate that this human cell-based test holds the potential to replace aspects of in vivo animal acute toxicity testing, particularly with reference to cosmetic ingredients.

SKOOL versus ZOOL: effects of orthographic and phonological long-term memory on nonword immediate serial recall.

In a now-classic study Besner and Davelaar (1982) reported an advantage of pseudohomophone (PSH) over nonword recall in a visual immediate serial recall (ISR) task, which remained under articulatory suppression (AS), and interpreted the findings as indicating PSH items obtain support from stored phonological long-term memory (LTM) representations even when phonological rehearsal is disrupted. However, one key question relating to this PSH effect remains: could the results have been contaminated by a potential confound of orthographic familiarity (i.e., PSH items often look like the word they sound like)? As a result, the present study examined the impact of orthography on PSH ISR. Our findings indicate that PSH accuracy was consistently higher for items that had an orthographic similarity to the parent word, and this effect did not interact with concurrent task. We therefore argue that PSH items in ISR obtain independent support from both orthographic and phonological LTM representations. The present study demonstrates the critical impact of orthographic LTM representations on visual nonword ISR, and we suggest that this may be a fruitful avenue for further research.

Orthography, phonology, short-term memory and the effects of concurrent articulation on rhyme and homophony judgements.

The role of phonological short-term memory (pSTM) in phonological judgement tasks of print has been widely explored using concurrent articulation (CA). A number of studies have examined the effects of CA on written word/nonword rhyme and homophone judgements but the findings have been mixed and few studies have examined both tasks within subjects. Also important is the influence of orthographic similarity on such tasks (i.e., items that share phonology often strongly overlap on orthography). Although there are reports of orthographic similarity effects (e.g., LOAD-TOAD vs. DIAL-MILE) on rhyme judgements, it is unknown whether (a) similar orthographic effects are present with homophone judgements, (b) the degree to which such orthographic effects interact with CA, and (c) the degree to which such orthographic effects interact with lexical status (words vs. nonwords). The present work re-examines these three issues in a within subject design. CA and orthographic similarity yielded subtle differences across tasks. CA impaired accuracy for both homophone and rhyme judgement, but only slowed RTs on the rhyme judgement task, and then only for words. Orthographic similarity yielded an increase in false positives for similar items and vice versa for dissimilar items, suggesting a general impact of an orthographically based 'bias' in choosing similar or dissimilar sounding items. This pattern was amplified under CA but only on the homophone judgement task. These results highlight important interactions between phonological and orthographic representations in phonological judgement tasks, and the findings are considered both with reference to earlier studies and several models of pSTM.