Volume 43, Issue 4 - August 2015

e cigarette paraphernaliaInnovative tobacco-related product testing.

See Comment by Robert D. Combes and Michael Balls


Editorial: Peer Review and the Three Rs: A Challenge to lntegrity?

Michael Balls

Peer review is undoubtedly an imperfect process, but there is no other acceptable way of attempting to ensure the highest standards in research and the publication of opinions and results.
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News and Views

ATLA Staff Writer

Cell Spheroids: Promising In Vitro Models
Alzheimer’s Disease Study with Human Volunteers
In Vitro Model of Developmental Toxicity
Crowdsourcing Toxicity Testing
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CAAT News and Views


A History of CAAT: The First 28 Years (1981–2009)
Katya Tsaioun to Replace Martin Stephens as Secretariat of the Evidence-based Toxicology Collaboration (EBTC)
The Silent Monkey Victims of the War on Terror
Meet Your Biotech SMEs (European Parliament)
Upcoming Events
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Summary and Analysis of the Currently Existing Literature Data on Metal-based Nanoparticles Published for Selected Aquatic Organisms: Applicability for Toxicity Prediction by (Q)SARs

Guangchao Chen, Martina G. Vijver and Willie J.G.M. Peijnenburg

This review establishes an inventory of existing toxicity data on nanoparticles (NPs) with the purpose of developing (Quantitative) Structure–Activity Relationships for NPs (nano-[Q]SARs), and also of maximising the use of scientific sources for NP risk assessment. From a data search carried out on 27 February 2014, a total of 910 publications were retrieved from the Web of Science™ Core Collection, and a database comprising 886 records of toxicity endpoints, based on these publications, was built. The test organisms mainly comprised bacteria, algae, yeast, protozoa, nematoda, crustacea and fish. The NPs consisted mostly of metals, metal oxides, nanocomposites and quantum dots. The data were analysed further, in order to: a) categorise each toxicity endpoint and the biological effects triggered by the NPs; b) survey the characterisation of the NPs used; and c) assess whether the data were suitable for nano-(Q)SAR development. Despite the efforts of numerous scientific programmes on nanomaterial safety and design, our study concluded that lack of data consistency prevents the use of experimental data in developing and validating nano-(Q)SARs. Finally, an outlook on the future of nano-(Q)SAR development is provided.

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More Noise Does Not Mean More Precision: A Review of Aldenberg and Rorije (2013)

David R. Fox

This paper provides a critical review of recently published work that suggests that the precision of hazardous concentration estimates from Species Sensitivity Distributions (SSDs) is improved when the uncertainty in the input data is taken into account. Our review confirms that this counter-intuitive result is indeed incorrect.

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A Critical Assessment of the Scientific Basis, and Implementation, of Regulations for the Safety Assessment and Marketing of Innovative Tobacco-related Products

Robert D. Combes and Michael Balls

Our scientific, logistical, ethical and animal welfare-related concerns about the latest US Food and Drug Administration (FDA) regulations for existing and so-called ‘new’ tobacco products, aimed at reducing harmful exposures, are explained. Such claims for sales in the USA now have to be based on a wide range of information, a key part of which will increasingly be data on safety and risk. One of the pathways to achieve marketing authorisation is to demonstrate substantial equivalence (SE) with benchmark products, called predicates. However, the regulations are insufficiently transparent with regard to: a) a rationale for the cut-off date for ‘old’ and ‘new’ products, and for exempting the former from regulation; b) the scientific validity and operation of SE; c) options for product labelling to circumvent SE; d) the experimental data required to support, and criteria to judge, a claim; and e) a strategy for risk assessment/management. Scientific problems related to the traditional animal methods used in respiratory disease and inhalation toxicology, and the use of quantitative comparators of toxicity, such as the No Observed Adverse Effect Level, are discussed. We review the advantages of relevant in vitro, mechanism based, target tissue-oriented technologies, which an advisory report of the Institute of Medicine of the US National Academy of Sciences largely overlooked. These benefits include: a) the availability, for every major site in the respiratory tract, of organotypic human cell-based tissue culture systems, many of which are already being used by the industry; b) the accurate determination of concentrations of test materials received by target cells; c) methods for exposure to particulate and vapour phases of smoke, separately or combined; d) the ability to study tissue-specific biotransformation; and e) the use of modern, humanfocused methodologies, unaffected by species differences. How data extrapolation, for risk assessment, from tissue culture to the whole animal, could be addressed, is also discussed. A cost (to animal welfare)–benefit (to society, including industry and consumers) analysis was conducted, taking into account the above information; the potential for animal suffering; the extensive data already available; the existence of other, less hazardous forms of nicotine delivery; the fact that much data will be generated solely for benchmarking; and that many smokers (especially nicotine-dependents) ignore health warnings. It is concluded that, in common with policies of several tobacco companies and countries, the use of laboratory animals for tobacco testing is very difficult, if not impossible, to justify. Instead, we propose and argue for an integrated testing scheme, starting with extensive chemical analysis of the ingredients and byproducts associated with the use of tobacco products and their toxicity, followed by use of in vitro systems and early clinical studies (involving specific biomarkers) with weight-of-evidence assessments at each stage. Appropriate adjustment factors could be developed to enable concentration–response data obtained in vitro, with the other information generated by the strategy, to enable the FDA to meet its objectives. It is hoped that our intentionally provocative ideas will stimulate further debate on this contentious area of regulatory testing and public safety.

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FRAME is the Fund for the Replacement of Animals in Medical Experiments. It publishes ATLA. It also promotes the replacement of animals in laboratories through better science. Visit FRAME website
PiLAS is Perspectives in Laboratory Animal Science. It improves the quality of discussion about animal experimentation by giving scientists in all fields a place to exchange views. Read PiLAS