Acute toxicity testing of chemicals—Opportunities to avoid redundant testing and use alternative approaches

Abstract

Assessment of the acute systemic oral, dermal, and inhalation toxicities, skin and eye irritancy, and skin sensitisation potential of chemicals is required under regulatory schemes worldwide. In vivo studies conducted to assess these endpoints can sometimes be associated with substantial adverse effects in the test animals, and their use should always be scientifically justified. It has been argued that while information obtained from such acute tests provides data needed to meet classification and labelling regulations, it is of limited value for hazard and risk assessments. Inconsistent application of in vitro replacements, protocol requirements across regions, and bridging principles also contribute to unnecessary and redundant animal testing. Assessment of data from acute oral and dermal toxicity testing demonstrates that acute dermal testing rarely provides value for hazard assessment purposes when an acute oral study has been conducted. Options to waive requirements for acute oral and inhalation toxicity testing should be employed to avoid unnecessary in vivo studies. In vitro irritation models should receive wider adoption and be used to meet regulatory needs. Global requirements for sensitisation testing need continued harmonisation for both substance and mixture assessments. This paper highlights where alternative approaches or elimination of tests can reduce and refine animal use for acute toxicity requirements.

In VitroToxicity Evaluation of Engineered Cadmium-Coated Silica Nanoparticles on Human Pulmonary Cells

“…The identification of predictive in vitro toxicity assays is in line with the recommended attention that should be given to regulatory acceptance as means of promoting the use of alternative methods to animal testing in human safety assessment [27, 28]. …”

Contrast agent-free sonoporation: The use of an ultrasonic standing wave microfluidic system for the delivery of pharmaceutical agents

“…This may contribute, at least in some way, to the 3Rs philosophy (reduction, refinement, and replacement of animal experiments), 21 which is also in line with a national centred UK government-sponsored scientific organisation, NC3Rs. 22 Our experimental work aims to demonstrate the intracellular delivery of pharmaceutical agents to cardiac myoblasts by non-inertial CA-free sonoporation. An ultrasonic standing wave (USW) was generated within a biocompatible microfluidic device, which enables high cell viability to be maintained.…”

Working in partnership to advance the 3Rs in toxicity testing

“…The review pulls together the scientific rationale and opportunities for waiving data requirements; and highlights the current disparate regulatory approaches across various industry sectors that result in the potentially unnecessary use of animals (Creton et al, 2009b). Building on existing (but not universally accepted) information on redundancy, the review provides the global regulatory community with information with which to critically assess data requirements when considering the generation of acute toxicity data.…”