An Analysis of the Use of Animal Models in Predicting Human Toxicology and Drug Safety

  title={An Analysis of the Use of Animal Models in Predicting Human Toxicology and Drug Safety},
  author={Jarrod Bailey and Michelle Thew and Michael Balls},
  journal={Alternatives to Laboratory Animals},
  pages={181 - 199}
Animal use continues to be central to preclinical drug development, in spite of a lack of its demonstrable validity. The current nadir of new drug approvals and the drying-up of pipelines may be a direct consequence of this. To estimate the evidential weight given by animal data to the probability that a new drug may be toxic to humans, we have calculated Likelihood Ratios (LRs) for an extensive data set of 2,366 drugs, for which both animal and human data are available, including tissue-level… 
Predicting Human Drug Toxicity and Safety via Animal Tests: Can Any One Species Predict Drug Toxicity in Any Other, and Do Monkeys Help?
Data is presented from analyses of other species pairs, including nonhuman primates (NHPs), which support the previous conclusions and show that test results inferring an absence of toxicity in one species provide no evidential weight with regard to toxicity in any other species, even when data from NHPs and humans are compared.
An analysis of the use of animals in predicting human toxicology and drug safety : a review
It is concluded that dogs, mice, rats and rabbits are highly unreliable at predicting toxicity outcomes.
Human-based Systems in Drug and Chemical Safety Testing — toward Replacement, the ‘Single R’
  • R. A. Coleman
  • Biology
    Alternatives to laboratory animals : ATLA
  • 2014
The present review outlines the current state-of-the-art regarding in vitro, in silico and in vivo technologies, identifying strengths, weaknesses and opportunities, and goes on to address the prospect of achieving a single R, with some suggestions as to how to progress toward this goal.
Safety Assessment of Pharmaceuticals
  • J. G. Kenna, R. Ram
  • Biology, Medicine
    The History of Alternative Test Methods in Toxicology
  • 2019
Limitations of Animal Studies for Predicting Toxicity in Clinical Trials
Recent efforts to elucidate the scientific validity of animal-based drug tests by the pharmaceutical industry, pro-testing lobby groups, and animal welfare organisations
The data in these recent studies, as well as in the own studies, support the contention that tests on rodents, dogs and monkeys provide next to no evidential weight to the probability of there being a lack of human toxicity, when there is no apparent toxicity in the animals.
Safety Profile Based on Concordance of Nonclinical Toxicity and Clinical Adverse Drug Reactions for Blood Cancer Drugs Approved in Japan
The results suggested that ADRs in clinical trials could be predicted based on toxicity data obtained in animal tests, especially for some drugs with a low quantitative safety profile.


An Analysis of the Use of Dogs in Predicting Human Toxicology and Drug Safety
Likelihood Ratios for an extensive dataset of 2,366 drugs with both animal and human data, including tissue-level effects and Medical Dictionary for Regulatory Activities Level 1–4 biomedical observations show that the absence of toxicity in dogs provides virtually no evidence that adverse drug reactions will also be absent in humans.
The evaluation of anticancer drugs in dogs and monkeys for the prediction of qualitative toxicities in man
The usefulness of dogs and monkeys in predicting potential qualitative drug toxicity in man was examined retrospectively for twenty‐five anticancer compounds of diverse chemical and functional
Concordance of the toxicity of pharmaceuticals in humans and in animals.
The survey results support the value of in vivo toxicology studies to predict for many significant HTs associated with pharmaceuticals and have helped to identify HT categories that may benefit from improved methods.
Predictive value of animal models for human cytochrome P450 (CYP)-mediated metabolism: A comparative study in vitro
If hepatic xenobiotic-metabolizing characteristics were to be the sole reason for the selection of animal species for toxicity studies, then the rat might not be the most appropriate model to mimic human CYP activity patterns.
Role of the cytochrome P450 enzyme system in veterinary pharmacokinetics: where are we now? Where are we going?
The current state of knowledge regarding the role of the cytochrome P450 superfamily of enzymes in determining the metabolic profile of compounds administered to companion animals and to food-producing animal species is described.
First dose of potential new medicines to humans: how animals help
The principles and the available, albeit limited, evidence that support the design and conduct of preclinical studies in a way that permits effective and safe first-dose studies of potential new medicines in humans are reviewed.
Developmental Toxicity Testing: Protecting Future Generations?
  • Jarrod Bailey
  • Environmental Science
    Alternatives to laboratory animals : ATLA
  • 2008
It is argued that animal tests in these scientific areas do not provide reliable data that are predictive for human responses and, even if they did, the tests are too expensive and time-consuming for application to the very large number of substances that need to be tested.
Cheminformatics analysis of assertions mined from literature that describe drug-induced liver injury in different species.
This is the first study for chemical toxicity prediction that applied QSAR modeling and other cheminformatics techniques to observational data generated by the means of automated text mining with limited manual curation, opening up new opportunities for generating and modeling chemical toxicology data.
Induction of hepatic cytochrome P450 enzymes: methods, mechanisms, recommendations, and in vitro–in vivo correlations
In this review, the authors’ current understanding of the mechanisms of enzyme induction and the in vitro methods for assessing the induction potential of new drugs will be discussed and relevant issues and considerations surrounding proper study design and the interpretation of in vitro results are discussed.
Challenges in exploring the cytochrome P450 system as a source of variation in canine drug pharmacokinetics
An overview of what is currently known about canine CYPs is provided with the hope that it will encourage further exploration into this important area of research.