In Tamoxifen’s case, a drug first developed as a potential contraceptive languished for many years before its present application was found. Furthermore, its propensity to cause liver tumours in rats, a toxicity problem that thankfully does not carry over into humans, was not detected until after the drug had been on the market for many years. If it had been found in preclinical testing, the drug would almost certainly have been withdrawn from the pipeline.
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... numerous chemicals have been found to have potential toxicity/carcinogenicity in rat or mouse, which, we are reasonably certain, have little or no potential hazard in man. The reason for this is again species differences, for the biological defence mechanism which protects against toxic chemicals is most highly evolved in man, who therefore generally has a higher resistance to chemical toxicity and carcinogenicity than have rodents and other species.
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Yes, I think it is very clear to all of us who are engaged in the business of assessing toxicity data that, when volumes of data are proudly presented to us after a carcinogenicity study, showing that there was a tumour in this organ or that, we look at it and we scratch our heads, and we wonder what on earth we can make of it. This is especially true when huge doses are given, with nothing to suggest what would be expected at low doses. I think very often the carcinogenicity studies are a waste of everybody's time and a fearful waste of animals. They are conducted partly because we are not sure what to do instead, and partly because they are a political gesture and a very miserable one at that.
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During a chronic study the problem may be complicated by the presence of concomitant diseases; it is in fact known that acute inflammation or the presence of a tumor may affect the kinetics of chemical, thus altering their potential toxicity.
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George The official toxicity limit for humans is between one and one and half grams of cocaine depending on body weight. I was averaging five grams a day, maybe more. I snorted ten grams in ten minutes once. I guess I had a high tolerance.
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