Lack of Predictivity of the Rat Lethality (LD50) Test for Ecological and Human Health Effects

Rosenkranz, Herbert S.; Cunningham, Albert R.

doi:10.1177/026119290503300104

Cited by 6 publications

(2 citation statements)

References 62 publications

(64 reference statements)

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“…To date, the only regulatory tests for acute toxicity involve the use of animals. Methods such as the LD50, Up-and-Down Procedure and Fixed Dose Procedure are widely recognised as having significant scientific flaws and low relevance to human toxicology (3,4). In addition, ethical concerns and public pressure have driven the demand for scientifically and ethically advanced replacements -a sentiment embodied in recent legislation.…”

Section: Introductionmentioning

confidence: 99%

Non-animal Replacements for Acute Toxicity Testing

et al. 2015

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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.

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Section: Introductionmentioning

confidence: 99%

Non-animal Replacements for Acute Toxicity Testing

et al. 2015

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“…The use of surrogate assays to predict toxicity in higher species by QAAR methods has been recognised as a primary source to fill the existing data gaps in toxicological databases (8)(9)(10). Compared to in vivo testing, in vitro surrogates are more economical and more rapid, allowing extrapolations to other species and broadening knowledge about mechanisms of toxic action (MOA).…”

Section: Introductionmentioning

confidence: 99%

Comparative Quantitative Structure–Activity–Activity Relationships for Toxicity to Tetrahymena pyriformis and Pimephales promelas

et al. 2007

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An approach for predicting acute aquatic toxicity, in the form of a quantitative structure–activity–activity relationship (QSAAR), is described. This study assessed relative toxic effects to a fish, Pimephales promelas, and a ciliate, Tetrahymena pyriformis, and attempted to form relationships between them. A good agreement between toxic potencies (R2 = 0.754) was found for a chemically diverse dataset of 364 compounds, when using toxicity to the ciliate as a surrogate to that for fish. This relationship was extended by adding three theoretical structural descriptors of the molecules. The inclusion of these descriptors improved the relationship further (R2 = 0.824). The structural features that were found to improve the extrapolation between the toxicity to the two different species were related to the electron distribution of the carbon skeleton of the toxicant, its hydrogen-bonding ability, and its relative nitrogen content. Such a QSAAR approach provides a potential tool for predicting the toxicities of chemicals for environmental risk assessment and thus for reducing animal tests.

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Acute Toxicology Testing

2007

Principles of Toxicology Testing

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Lack of Predictivity of the Rat Lethality (LD50) Test for Ecological and Human Health Effects

Cited by 6 publications

References 62 publications

Non-animal Replacements for Acute Toxicity Testing

Non-animal Replacements for Acute Toxicity Testing

Comparative Quantitative Structure–Activity–Activity Relationships for Toxicity to Tetrahymena pyriformis and Pimephales promelas

Acute Toxicology Testing

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