Art Of Toxicology Research Articles

Hard Impact: Journal Impact Factor and JMT

Hard Impact: Journal Impact Factor and JMT

Recent developments in analytical toxicology: for better or for worse

When considering the state of the art in toxicology from an analytical perspective, the key developments relate to three major areas. (1) Forensic horizon: Today forensic analysis has broadened its scope dramatically, to include workplace toxicology, drug abuse testing, drugs and driving, doping, environmental and veterinary toxicology, etc. (2) Basic analytical issues, focusing on a strongly widening array of relevant substances and metabolites at ever decreasing levels in a large variety of matrices. (3) Validation and interpretation: Because forensic analyses may have severe, punitive consequences, validation of methods and approaches plus proficiency testing are of utmost importance. Also, interpretation of the analytical results must be done with prudence in view of chemical and biological diversity in society. This review discusses the various pros and cons in these developments.

Alternatives in Safety Testing: Progress or Uselessness?

Safety testing is a major responsibility of toxicologists. Toxicology is not only a science but also an art. The science of toxicology characterises the toxic potential of a given chemical entity, i.e. the intrinsic property which allows it to react with, and/or to be transformed by, a particular biological system. Based on such scientific data, the art of toxicology has to predict the risk, i.e. the probability that a particular adverse event will occur during a stated period of time or result from a particular challenge. Until now, the science of toxicology has relied almost exclusively on animal tests, the protocols of which are described in directives and regulations. As stated in an Editorial in ATLA (1) the question that toxicologists now have to tackle is, “can non-animal toxicity studies become genuine replacement alternatives …” for assessing risk adequately? Indeed, the science of toxicology has developed, and continues to develop, new approaches (alternatives) to characterise, in well-defined in vitro models (including, for the first time, human models), the toxic potential of chemicals, namely, cytotoxicity, organ-specific effects, modulation of metabolic functions, interference with cell-mediated processes, metabolic activation, etc. But the question remains, what about the art of toxicology? Is it realistic to predict that such new scientific data will, in time, be accepted by regulators for risk evaluation? If these data are to be accepted, we believe that, instead of the present trend towards a regulation-required “protocol toxicology”, toxicologists will have to impose a stepwise decision-tier approach based on the systematic and sequential progression of scientifically justified and rigorously performed investigations, the results of which will be thoroughly and realistically evaluated by experts. It has to be recognised that scientific knowledge has advanced far enough to permit a focus on mechanisms, so that alternatives are fully accepted, no longer as a supplement to a check-list approach, but as a full part of the scientific expertise.

Principles for a pragmatic approach to the regulatory acceptance of alternative tests

Toxicity studies are conducted with a view to identifying and assessing human or environmental hazards. Thus, the key issues are those of which, and how much, information is considered necessary to make a reliable and valid assessment, and to what extent alternative tests can contribute to this assessment. In this respect, the following fundamental aspects are of relevance. Toxicology as a science focuses on the identification and characterization of adverse effects following exposure to chemicals by integrating all available information, including physicochemical properties, all observed adverse effects in all studies, toxicokinetics and toxicodynamics, exposure conditions, and more. Most of this information is generated in tests conducted according to internationally accepted guidelines. Next, the art of toxicology is to evaluate and extrapolate the information acquired and then to assess human and environmental health hazards. Thus, the validity of any hazard prediction relies both on the collected data and on the craftsmanship of the assessor. Unfortunately, the experts involved in the science of toxicology are frequently not involved in the art of toxicology. As a consequence, the artist who is used to his set of fine tools, which he bought a long time ago and with which he always managed to create the ‘sculpture’ of hazard assessment, is now suddenly asked to use some new and rather different tools. It is understandable that this may bring about some opposition. In addition to these fundamental aspects, there are also political aspects to the issue of acceptance of alternative tests. These and other pitfalls have contributed to the author's opinion that progress in this respect can only be made by introducing the alternative tests without, at least for the time being, deleting the trusted existing ones.

The search for alternatives

Animal welfare and antivivisection groups have protested against animal research for the last 150 years. However, they have recently (ca. 20 years ago) injected a new element into the debate by pressing for the development and application of alternatives. By this, they mean the development of techniques which could replace or reduce the use of laboratory animals, or the refinement of existing techniques to reduce animal suffering. Animal welfare concerns have focused on toxicology testing in particular. Of course, the state of the art in toxicology has advanced considerably in the last 20 years and some of the changes have resulted in a reduction of the use of animals. Nevertheless, the animal welfare movement seeks a more specific program which will review testing guidelines and support the development of new techniques which will reduce or eliminate animal use. Carcinogen detection, Draize eye irritancy testing, and LD50 testing are three specific areas where the pressure for alternatives development has been strongest. The prospects for alternatives in each of these three are briefly discussed together with one or two comments about possible future trends.

The Search for Alternatives

Abstract Animal welfare and antivivisection groups have protested against animal research for the last 150 years. However, they have recently (ca. 20 years ago) injected a new element into the debate by pressing for the development and application of alternatives. By this, they mean the development of techniques which could replace or reduce the use of laboratory animals, or the refinement of existing techniques to reduce animal suffering. Animal welfare concerns have focused on toxicology testing in particular. Of course, the state of the art in toxicology has advanced considerably in the last 20 years and some of the changes have resulted in a reduction of the use of animals. Nevertheless, the animal welfare movement seeks a more specific program which will review testing guidelines and support the development of new techniques which will reduce or eliminate animal use. Carcinogen detection, Draize eye irritancy testing, and LD50 testing are three specific areas where the pressure for alternatives development has been strongest. The prospects for alternatives in each of these three are briefly discussed together with one or two comments about possible future trends.