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Abstract. An increasing concern over the LDso study has become apparent over the years and even more so recently in Britain with the Home Office Publication on the subject and comments and opinions expressed in the National Press. Particularly with respect to the Pharmaceutical and Agrochemical Industries, the number of animals used depends on the number required to satisfy the Regulatory Authorities. Is there a scientific rationale for using the number of animals required? Data is presented justifying the use of smaller numbers of animals for establishing the acute toxicity of a chemical.

1 The potential effects of new drugs on the digestive system can be examined in a number of model systems of which intestinal motility in the mouse and/or gastric emptying in the rat are examples recommended for safety pharmacology evaluation. 2 Intestinal motility, assessed by the transit of carmine dye in the mouse and gastric motility, assessed by stomach weight in the rat, were examined using a range of clinical drugs or potent pharmacological agents known to affect gastrointestinal function. Assessment of both models in the guinea-pig was also evaluated. 3 Activity was demonstrated with codeine, diazepam, atropine and CCK-8 (all of which inhibited gastric function). However, neither model gave consistent and reliable results with the remaining reference compounds, namely metoclopramide, bethanechol, cisa-pride, deoxycholate, carbachol and domperidone. 4 In conclusion, this investigation questions the usefulness of simple models of gastrointestinal transport in the rodent as a means of detecting potential effects of a new drug on the digestive system. This finding should be of concern to the pharmaceutical industry as these simple models are routinely used as part of a regulatory safety pharmacology `package' of studies.

Summary1. An automatic method for doing assays on superfused isolated tissues has been developed using the Autoanalyser sample turntable. 2. Responses in the range used for assays are independent of the preceding responses when elicited at 1 min intervals. A longer interval was found to be necessary when using the conventional immersion method. 3. The index of precision was similar to that reported for other superfusion methods. 4. The assay method behaved as though it were assaying histamine selectively in two samples of material released by the anaphylactic reaction of passively sensitized guinea-pig lung. Responses to anaphylactically released material were also independent of the preceding response at 1 min intervals. 5. Some theoretical considerations are discussed concerning the arrangement of doses, and the interpolation of results, in 2 +1 dose assays. The object was to maximize speed while still allowing a valid estimate of the potency and its error.

assume that people in coastal retirement areas are automatically healthier than those in inner city areas. The current allocation of resources already provides extra money for inner cities. Here in the north west the district allocation to Blackpool for 1991-2 was C107m for a population of 321000, while central and north Manchester received ,C163m for a population of 260000. In a review of capitation funding Raftery noted a projected continuing population drift away from inner cities to coastal retirement areas.' I suggest that the capitation funding formula should remain as simple as possible, without any sociological tinkering. Charlton concluded, "redistribution of income and other resources has little to offer in improving the national health: it is merely robbing Peter to pay Paul."4 P J N HOWORTH Consultant chemical pathologist