During the past 20 years the EU legislation for the notification of chemicals has focussed on new chemicals and at the same time failed to cover the evaluation of existing chemicals in Europe. Therefore, in a new EU chemicals policy (REACH, Registration, Evaluation and Authorization of Chemicals) the European Commission proposes to evaluate 30,000 chemicals within a period of 15 years. We are providing estimates of the testing requirements based on our personal experiences during the past 20 years. A realistic scenario based on an in-depth discussion of potential toxicological developments and an optimised "tailor-made" testing strategy shows that to meet the goals of the REACH policy, animal numbers may be significantly reduced below 10 million if industry would use in-house data from toxicity testing, which are confidential, if non-animal tests would be used, and if information from quantitative structure activity relationships (QSARs) would be applied in substance-tailored testing schemes. The procedures for evaluating the reproductive toxicity of chemicals have the strongest impact on the total number of animals bred for testing under REACH. We are assuming both an active collaboration with our colleagues in industry and substantial funding of the development and validation of advanced non-animal methods by the EU Commission, specifically in reproductive and developmental toxicity.
Five pigeons were trained to perform a discrimination task allowing variability of reinforced response patterning. The task consisted of moving a stimulus light within an 4 X 4 matrix of lights from the top left position to the bottom right position by pecking on two keys in succession in order to obtain a reinforcement. A peck on one key moved the light one position to the right and a peck on the other key moved it one position down. After preliminary training on alternating fixed-ratio 3 schedules of reinforcement, the birds could peck on either key in any order, but more than three responses on a key resulted in a blackout followed by the return of the stimulus light to the start position. Results indicate that initially the birds used a wide variety of response patterns to obtain reinforcement, but with continued practice, response patterns became more stereotyped.
Uniform flood frequency guidelines in the United States currently recommend fitting a Pearson (P3) distribution to the logarithms of annual maximum flood flows. As a result, a plethora of procedures have been recommended for obtaining unbiased plotting positions and unbiased estimates of the skew coefficient and for inverting the cumulative distribution function of a P3 variate. These developments are precisely the ingredients required for the construction of P3 probability plots. Using Monte Carlo simulation, we develop a probability plot correlation coefficient (PPCC) hypothesis test for the P3 distribution. Power studies are performed to evaluate the ability of the test to discriminate among competing distributional alternatives and to enhance our understanding of why the P3 distribution often appears to provide such a good fit to observed flood flow data. A new estimator of the skew coefficient is presented which, unlike the biased and unbiased moment estimators, is unbounded and has significantly lower root mean square error than the moment estimators for highly skewed samples.
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