The importance of the Three Rs concept of Russell and Burch is discussed, and it is argued that, while reduction and refinement can offer significant gains in terms of animal welfare and the quality of the data obtained from animal experiments, only replacement can provide a satisfactory escape from the high fidelity fallacy which underlies the inadequacy of animal procedures, not only in fundamental research on human diseases, but in particular, in the testing of chemicals, drugs and other chemical products in support of the enhancement and protection of human health. Some reasons for encouragement are discussed, but some current causes for concern are also identified, notably those related to the introduction of the EU REACH system for "new" and "existing" chemicals.

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The veterinary profession requires that students are well trained in clinical skills and have a solid basis of theoretical knowledge. Furthermore, the guardians of patients - especially in small animal practice - and society as a whole, expect the veterinarian to treat patients with care and compassion. The concept of care as a central skill is not always emphasised in veterinary education, but a caring approach may better enable the veterinarian to diagnose and treat his patients. This presentation discusses the reasons to look upon care and compassion as essential clinical skills to be developed and prioritised within veterinary education. The different teaching tools and approaches that are, in the author's opinion, best suited to develop such skills are discussed, as well as teaching methods that may be counter-productive to these objectives. In particular, the role of animal experiments within education is challenged, and their role in potentially limiting the number of motivated students wanting to enter veterinary education and the profession is discussed.

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The time score for 50% cell viability (50% effective time; ET50) is used as the index of skin irritation evaluated by a three-dimensional human skin model, such as TESTSKINTM and Vitrolife-Skin^TM. ET50 is conventionally estimated by linear interpolation of measurements at two time points, which yields cell viabilities above and below 50%. This simple method is problematic in that biased estimates are occasionally obtained and confidence intervals cannot be appropriately constructed.
We compared four estimation methods including a logistic regression method, a log-time regression method, a linear regression method and a newly proposed two-stage method through a Monte-Carlo simulation study in small sample sizes due to the experimental restrictions. The logistic regression method provides almost unbiased estimates, although the confidence interval for ET50 is occasionally not obtained. The log-time regression method and the linear regression method provide positive biased estimates, although the confidence interval for ET50 is obtained in any case. The two-stage method is reasonable, in which the log-time regression method is adopted only if the logistic regression method cannot construct a confidence interval for ET50.

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The effects of dental biomaterials on the differentiation of embryonic stem cells of the mouse cell line D3 (ES-D3 cells) were examined using the embryonic stem cell test (EST). Three study parameters, the rate of differentiation into contracting cardiomyocytes, the 50% cell viability of ES-D3 and BALB/c 3T3 cells, and the clone A31 (3T3 cells), were used to determine the embryotoxicity. Of the eighteen dental monomers tested, Bis-GMA (6F) and MTYA were classified as weakly embryotoxic, and 2.0-EPDMA, 3.0-EPDMA, 4.0-EPDMA, 1.6-ADMA, 1.8-ADMA, 1.10-ADMA, 6-HHMA, MEPC, Phosmer M, BPE-1300, BSNa, EDMABA, GAM, GMR, PTSNa, and QTX were evaluated as nonembryotoxic. However, none of the monomers tested were found to be strongly embryotoxic.
Our results suggest that further intensive studies on the embryotoxicity of dental biomaterials are needed in addition to examination of conventional biological aspects from the perspective of biological safety.

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Björn Ekwall, MD, Ph.D., died on the 19th of August 2000 after a long illness. He was born in Uppsala in 1940. In 1960 he attended the Uppsala University Medical School and in 1969 he obtained his MD. After a short time as a G.P., he became lecturer at the Department of Anatomy at Uppsala University. Between 1970 and 1980 he worked for his Ph.D. in toxicology. His research consisted of large scale testing, or rather screening, of chemical toxicity for cultured cells in simple test systems. He made a first effort to evaluate the relevance of the cytotoxicity for human systemic toxicity. …

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