The errors of vivisection part 2
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Animal-tested products can seriously damage your health |
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Please note this article is in two parts. A menu to return to Part 1 is in the above menu and at the end of this page.
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Note: Author's analysis of the following data is at the end of the section.
CONTINUED FROM PART 1
Zipeprol.
In 1984 a Milan poison control centre reported 32 patients suffering severe neurological side-effects following an overdose with zipeprol, a cough suppressant.[1] Symptoms included seizures and comas. Animal testing had given no warning of severe neurological problems despite higher doses being given to the animals that were used.[2]
[1] C. Moroni, et al, Lancet, 7 January 1984, p.45.
[2]D. Cosnier, et al, Drug Research, 1976, vol. 26, pp.848-854. G. Rispat, et al, Drug Research, 1976, vol. 26, pp.523-530.
Evicromil.
This was submitted for clinical (i.e., human) trials as an antiasthmatic after being tested on mice, rats, hamsters, rabbits, ferrets, squirrel monkeys, cynomolgus monkeys, stump- tail monkeys and baboons. Despite giving the animals doses many times greater than would be taken by humans, no harmful effects were noted, including the liver.[1] However, 20% of patients participating in the trial developed symptoms of liver damage, which prevented any further development of the drug.[2] Subsequent tests showed that liver toxicity could only be induced in dogs.[1,2]
[1]D. V. Parke, in Animals and Alternatives in Toxicity Testing, eds., M. Balls, et al (Academic Press, 1983).
[2]C. T. Easton, et al, Regulatory Toxicology and Pharmacology, 1990, vol.11 pp.288-307.
Fenclozic acid.
During clinical trials (i.e., on humans), ICI's anti-arthritic drug fenclozic acid produced jaundice in some patients. This was unexpected as testing which was undertaken on rats, mice, dogs and monkeys had given no hint of liver problems.[1] Not content with these results, there were further experiments with rabbits, guinea pigs, ferrets, cats, pigs, horses, neonatal rats and mice, along with a different strain of rat: yet again, no evidence of liver damage could be found.[1]
The ICI researcher commented: 'the quite unexpected onset of jaundice in a few patients caused withdrawal of the drug from humans and initiated a vast programme of experimental work. This search for hepatotoxicity [liver damage] in different species or any indication of its likelihood has so far been unrewarding [in other words, unsuccessful].
[1]S. J. Alcock, Proceedings of the European Society for the Study of Drug Toxicity, 1971, vol. 12, pp.184-190.
Ketoconazole.
In 1985, Britain's Committee on Safety of Medicines issued a warning about serious liver damage associated with the antifungal drug ketoconazole (Nizeral).[1] The Committee referred to 82 cases, with 5 deaths. The warnings followed a similar action by the American FDA in 1982.[2]
Despite this, no evidence of liver toxicity was found in the animal testing.[3]
[1]Lancet, 12 January 1985, p.121.
[2]C. B. M. Tester-Dalderup in Meyler's Side-Effects of Drugs, 11th edn, ed. M. N. G. Dukes (Elsevier, 1988).
[3]J. K. Heiberg and E. Svejgaard, British Medical Journal, 26 September 1981, p.825.
Nutrition.
During the early part of the previous century there was interest in the possibility that a lack of food during childhood might interfere with the development of the brain. Regrettably almost of the research was carried out on animals which showed that starving baby or adult rats had no effect on the brain. The issue was abandoned and not revived until the late 1950s when children with histories of undernutrition were found to persistently underachieve.[1]
Researchers then realized that the earlier animal testing had not taken 'brain growth spurt' into account, this being the time of fastest growth when the brain is most vunerable. Additionally, the timing varies between the different species, i.e., in human babies the brain growth spurt begins during the final period of pregnancy and lasts for about a year, whereas in guinea pigs, it occurs almost wholly during the foetal period, and yet in rats, it occurs during the first three weeks after being born.[2]
Despite the number of starving humans in the world today, there appears to be no shortage of funds for vivisectors who claim to be researching early life undernutrition in animals.
[1]J. Dobbing in Early Nuitrition and Later Behaviour, ed. J. Dobbing (Academic Press, 1987).
[2]J. Dobbing and J. L. Smart, British Medical Bulletin, 1974, vol. 30, pp.154-168.
Eraldin.
Eraldin (Practolol), marketed during the 1970s, was said to be 'particularly notable for the thoroughness with which its toxicity was studied in animals, to the satisfaction of the regulatory authorities'.[1]
In time, serious effects began to be noted, i.e., skin, eye and abdominal disorders. In some cases, patients suffered blindness; sclerosing peritonitis also occurred, resulting in 23 deaths being reported.[2] The manufacturers (ICI) paid compensation to over 1000 victims.[3]
The side-effects of the drug (for the treatment of heart conditions) were not predicted by the animal testing that was conducted. Moreover, subsequent to the drug being withdrawn from the market in 1976, it has not been possible to replicate the side- effects in laboratory animals.[1]
[1]M. Weatherall, Nature, 1 April 1982, pp.387-390.
[2]G. R. Venning, British Medical Journal, 15 January 1983, pp.199-202. 22 January 1983, pp.289-292.
[3]A Question of Balance, Office of Health Economics, 1980.
[4]F. H. Gross and W. H. Inman, Drug Monitoring (Academic Press, 1977).
Cortisone: the eye.
One of the principal side-effects of treating the eye with steroids is glaucoma (high pressure arises within the eye which can lead to loss of sight). And yet when corticosteroids were used in ophthalmology, the animal testing conducted indicated that cortisone did not affect the pressure within the eye.[1]
Later attempts to induce glaucoma in monkeys and rabbits were either difficult or impossible.[2] One group of researchers admitted to: 'the differing response of the eye of man and animals to repeated topical [surface] application of corticosteroids'. They added 'Such a procedure is without effect on tension of the eye of many experimental mammals, but increases tension in the human eye'.[3]
Another side-effect of using steroid treatment which is difficult to replicate in the laboratory animal is the cataract. While slight changes in the lens of the rabbit's eye have been produced - after repeated high doses - they do not mimic the severity of the condition as found in humans.[2]
[1]L. H. Leopold, et al, American Journal of Ophthalmology, 1951, vol. 34, pp.361-371.
[2]W. M. Grant, Toxicology of the Eye, 2nd edn (Charles Thomas, 1974).
[3]B. Ballantyne and D. W. Swanston in Current Approaches in Toxicology, ed. B. Ballantyne (Wright and Sons, 1977).
Talcum powder.
When experiments, using vast amounts of talcum powder, were conducted on animals, these suggested that using talcum powder presented no danger. In 1977 hamsters were exposed to high grade cosmetic talc at nearly two thousand times the amount that babies would encounter, and yet there was no damage to the lungs.[1] Another experiment in the same year involved rats being forced to breathe talc at doses nearly six thousand times the amount used in infant care; despite the amount used, there was only a slight effect on the lungs.[1]
However, subsequent to this time the medical profession had to issue warnings about using talc, e.g. in 1991 physicians at one hospital in Southern England warned that inhaling babies' talcum powder could be fatal.[2] Eight deaths were attributed to inhalation of talc.
[1]Lancet, 25 June 1977, pp.1348-1349.
[2]P. W. Pairaudean, et al, British Medical Journal, 18 May 1991, pp.1200-1201.
CS Gas.
Animal experimentation was responsible for providing incorrect and dangerous information about CS gas. When CR was applied to a rabbit's eye, only 'minor transient changes' occurred in respect of pressure in the eye. However, when a smaller amount was applied to a human eye, this resulted in a 40% increase in pressure in 5 minutes - while in rabbits, this only produced a 3% rise after 10 minutes.[1]
Tests found that human beings are 18 times more sensitive to CS than rabbits, and 90 times more sensitive to CR, another irritant.[2]
Tests involving application to the skin showed CR was a more potent irritant than CS and yet the very opposite was found when tested on rodents.[3] The research also determined that VAN, another sensory irritant, was less potent than CR which, once again, was the very opposite when tested on animals.
[1]B. Ballantyne, et al, in Current Approaches in Toxicology, ed. B. Ballantyne (Wright and Sons, 1977).
[2]D. W. Swanston in Animals and Alternatives in Toxicity Testing, eds. M. Balls, et al (Academic Press, 1983).
[3]R. W. Foster, et al, Pain, 1986, vol. 25, pp.269-278.
Fluoride.
Fluoridation of the water supply is considered to be a primary reason for the decline in dental decay. The adding of fluoride to the water supply does not appear to have caused any health problems.[1]
However, experimentation involving rats gave some indication that it might cause cancer,[2] and yet after an intensive study, the American DHHS (Dept. of Health and Human Services) reported that it had not found any evidence of fluoride causing cancer. Tests involving animals have also suggested other detrimental effects, but the DHHS reported that different species react divergently to fluoride and this made it difficult to apply to humans.[3]
[1]E.g., R. Peto and R. Doll, The Causes of Cancer (OUP, 1981).
[2]Journal of NIH Research, 1991, vol. 3, p.46.
[3]C. Anderson, Nature, 28 February 1991, p.732.
Coumarin.
Coumarin is obtained from the tonka bean, having been used for many years, in consumer items and as a therapeutic agent. However, in the 1950s, there were questions concerning its safety due to animal experimentation that resulted in liver damage in rats. Because of this, coumarin was prohibited as a food flavouring agent.[1]
Later research revealed there was a considerable variation in reactions by different species, e.g. although dogs suffered liver toxicity (as rats), there were only slight effects in baboons.[2] Furthermore those amounts which damaged the liver of rats were harmless to gerbils.[3] The nonsense of vivisection was further demonstrated when it was found that different strains of the same species reacted differently to coumarin.
Patients who receive coumarin, even in high doses, for therapeutic reasons, rarely experience liver toxicity,[1] and rats and dogs are therefore now viewed as unreliable models for testing the substance as they metabolize it in totally different ways.[1,2,3]
[1]J.H. Fentum, et al, Toxicology, 1992, vol. 71, pp.129- 136.
[2]J. G. Evans, et al, Food and Cosmetic Toxicology, 1979, vol. 17, pp.187-193.
[3]W. Endell and G. Seidsel, Agents and Actions, 1978, vol. 8, pp.299-302.
Formaldehyde.
Concern for those people who worked with formaldehyde arose after it was discovered that the substance caused cancer in rats.[1] Despite this, epidemiological studies did not give any indication of cancer arising in such people: additionally, monitoring of workers also found no evidence of this danger.
In fact the rats had been forced to breathe high doses - 7-15 times the amount that workers inhaled - resulting in formaldehyde causing tissue damage and cancers in them.
[1]P. Grasso, Journal of the Royal Society of Medicine, 1989, vol. 82, pp.470-473.
Epilepsy models.
Vivisectors have produced numerous methods of producing fits in laboratory animals; the reason for this is because no particular method is wholly trustworthy.[1]
After suggestions that high amounts of aspartame could cause seizures in some people, the London Institute of Psychiatry conducted experiments, sponsored by Nutrasweet Company and the Wellcome Trust, which involved flashing lights to produce fits in photosensitive baboons. In fact aspartame had no effect on the baboons although conflicting evidence has arisen in other animals. For example aspartame enhances chemically-induced convulsions in mice, but has no effect on electric-shock-induced or sound-induced seizures in these animals.[2]
Similar variations are found with different species. Although the drug THIP reduced convulsions in mice and baboons, it was ineffective when used with epileptic patients.[3]
[1]R. S. Fisher, Research Reviews, 1989, vol. 14, pp.245- 278.
[2]B. S. Meldrum, et al, Epilepsy Research, 1989, vol. 4, pp.107.
[3]Lancet, 26 January 1985, pp.198-200.
Glass Fibre.
Products made from glass wool were produced for decades with animal testing suggesting no health risk. Experiments involving rats, guinea pigs, rabbits and monkeys who were forced to breathe in glass wool fibres showed no damage to lungs.[1]
Subsequent tests during the 1980s confirmed 'an increase in lung tumours or mesothelioma has not been observed following long-term inhalation studies in several animal species including rats, hamsters, guinea pigs, mice, monkeys and baboons, exposed to glass fibres, glass wool or mineral wool'.[2]
Those experiments when rats developed cancer were dismissed as having no relevance for human health. This was due to the fibres being implanted into the membrane of the animal's lung which is in contrast to how humans become exposed, i.e., through breathing; additionally, rats are known to develop cancer when solid substances are implanted in their bodies.[1]
However, in 1991 the American Occupational Safety and Health administration declared that products made of glass fibre were a potential cancer risk.[3] This was after studies involving people working with glass fibre showed an increased risk of lung cancer. In Occupational Lung Disorders, Raymond Parkes notes that 'the production of malignant tumours in animals by direct implantation experiments is unlikely to have any relevance to human exposure'.
[1]Rep. in R. Parkes, Occupational Lung Disorders (Butterworths, 1982).
[2]C. S. Wheeler, Toxicology and Industrial Health, 1990, vol. 6, pp.293-307.
[3]Letter from G. F. Scannell, assistant secretary for OSH, Washington DC, to Richard Munson, Chairman of Victims of Fibreglass, 6 May 1991. The Guardian, 20 July 1991.
Depo-Provera.
In the 1960s, women who used the steroid Depo-Provera to deal with premature labour found that there was a delay in returning to fertility after their babies were born. Because of this, there was an investigation as to whether it could be used as a contraceptive.[1]
When tested on beagle dogs there was a range of serious side- effects including abnormal growths, breast cancer and death from pyometra (pus building up in the uterus), and yet none of these side-effects occurred in women who used Depo-Provera.[2] Researchers could only say that these side-effects were due to the physiological differences between human beings and dogs.[1]
In fact high doses of Depo-Provera can cause cancer in monkeys but the relevance of this is questioned as the tumours arise from a type of cell not found in women. Ironically, the type of cancer produced in monkeys is actually successfully treated by Depo- Provera in women.[1]
In 1991, the Lancet called for certain countries to 'reassess' their existing policies on Depo-Provera as they might be depriving women of a 'reliable, effective and safe method of contraception'.[2] Shortly afterwards, the American FDA then approved Depo-Provera as a long-acting contraceptive for women to use.
[1]Bulletin of the World Health Organisation, 1982, vol. 60, pp.199-210.
[2]Lancet, 5 October 1991, pp.856-857.
Silicosis.
During the late 1930s researchers discovered that the inhalation of metallic aluminium prevented silicosis in rabbits.[1] Consequently, this was used as a means of treating and preventing silicosis in workers,[2] who had to pass through an aluminium dusting chamber in which they inhaled the powder.
In the following decade, studies revealed the process did not work and the Industrial Pulmonary Disease Committee of Britain's Medical Research Council advised against this procedure being used.[3]
In fact the 'treatment' had considerable dangers. While large amounts of aluminium were found to be harmless to animals,[4], lung damage and cancer were reported amongst those working with aluminium.[5] Further studies have shown that Canadian workers who inhaled aluminium powder to prevent silicosis, have symptoms that agree with the idea that aluminium may produce Alzheimer's Disease.[6]
[1]J. J. Denny, et al, Canadian Medical Association Journal, 1939, vol. 40, p.213.
[2]W. R. Parkes, Occupational Lung Disorders, (Butterworths, 1982).
[3]M. C. S. Kennedy, British Journal of Industrial Medicine, 1956, vol. 13, pp.211-223.
[4]L. U. Gardner, et al, Journal of Industrial Hygiene and Toxicology, 1944, vol. 26, pp.211-223.
[5]M. J. Ellenhorn and D. G. Barceloux, Medical Toxicology (Elsevier, 1988).
[6]Lord Walton of Detchant, Journal of the Royal Society of Medicine, 1992, vol. 85, pp.69-70.
Diet and cancer.
Studies of people of different nationalities have revealed that the consumption of too much fat, particularly saturated fat, can lead to cancer of the colon. In contrast, animal experimentation, while confirming excessive fat can be dangerous, indicate that it is not saturated but polyunsaturated fat which is responsible.[1]
Clinical (i.e., human) studies have also shown that a high fibre diet is preferable for health but when tested on animals, there have been conflicting results: some tests have indicated a higher risk of cancer, whereas others suggest a lower risk.[2] Additionally, studies have shown diets which are high in animal protein are hazardous,[3] and yet animal testing indicates this protein is of no relevance.[2]
Human studies confirm that diets which include fruit and vegetables offer protection against colon cancer. However, the natural substances which fruit and vegetables have evolved to ensure protection against predators, actually produce cancer when administered to mice and rats.[4]
[1]J. L. Freudenheim and S. Graham, Epidemiologic Reviews, 1989, vol. 11, pp.229-235.
[2]D. Galloway, Cancer Surveys, 1989, vol. 8, pp.169- 188.
[3]B. Armstrong and R. Doll, International Journal of Cancer, 1975, vol. 15, pp.617-631.
[4]P. H. Abelson, Science, 21 September 1990, p.1357.
Prednisone.
Although Prednisone is a useful drug for treating leukaemia and other cancers which occur in human beings, it does not work in respect of animal tumours, and this includes two types of leukaemia in mice.[1]
Prednisone is even more effectual when used with other anti- cancer medications although yet again animal experimentation provided spurious results, i.e., of six combinations which showed an improvement in health, only one of these was predicted by animal testing.[1]
The background of Prednisone provides further examples of animal testing delaying effective medicine. When researchers claimed they could cure human cancer with adrenal gland extracts in the 1930s, the result was animal testing which was negative and the treatment was therefore jettisoned.[2] It was only later when researchers confirmed that adrenal extracts could be useful in combating some cancers that human trials led to such analogues as Prednisone.
[1]R. J. Johnson and A. Goldin, Cancer Treatment Reviews, 1975, vol. 2, pp.1-31.
[2]B. Reines, Cancer Research on Animals: Impact and Alternatives, (Chicago: NAVS, 1986).
Polio.
Despite the fanciful claims made by pro-vivisectionists that polio is an example of how vivisection can combat human illness, the reality is that animal experimentation delayed a proper insight of polio for many years.[1]
In 1908 there was the announcement that the polio virus had been discovered. Tissue from an infected human resulted in spinal cord disease when injected into monkeys; the animals died with one developing paralysis in both legs. However, negative results had arisen with rabbits, guinea pigs, and mice and it was little more than chance that the researchers had selected Old World monkeys which are susceptible to the disease: if they had used New World monkeys they would have had different results from the experimentation as these monkeys are resistant to the disease.
Believing that a replica of the human form was now available, researchers concentrated on artificially inducing the disease in monkeys; these experiments gave support for the view that the poliovirus entered the system through the nose and it only attacked the CNS (Central Nervous System].[1,2]
And yet in 1907, a study of human cases had revealed that poliomyelitis was not wholly a disease of the CNS, and the gastrointestinal tract was the most likely route of the infection[1]. By 1912, other studies confirmed the intestinal tract as the means by which infection entered the body.
Regrettably because animal experimentation dominated research, most researchers, up to 1937, rejected the view that polio was an intestinal disease. The fact of whether the virus entered the body through the mouth or the nose was of course of major importance as the route dictated the best action to prevent its spread. In 1937, a nasal spray which prevented infection in monkeys was produced; not surprisingly it failed, also sometimes having a lasting side-effect, when it was used by human beings.[1]
It was only after the idea of the nasal route of infection, based on animal testing, was rejected and it was recognized that the polio virus entered the mouth and first resided in the intestines that a vaccine, orally administered could be produced. A solution was further delayed when monkeys were then used in time-consuming and expensive testing for the presence of the virus; tissue was inoculated into monkeys who were then examined for spinal cord damage. Progress was made when in 1949, Enders, Weller and Robins showed that the polio virus could be grown in human tissue culture; in this environment changes in infected cells, produced by the virus, could be monitored by microscope. If this alternative had been adopted an at earlier stage, there can be no doubt that progress would have been quicker, and both animal and human suffering would have been far less. However, valuable time was wasted through vivisectors asserting that the virus could only grow in the CNS, and the 'monkey model' of polio delaying the tissue culture development which was crucial to discovering a vaccine.[1,3]
[1]J. R. Paul, A History of Poliomyelitis (Yale University Press, 1971).
[2]H. F. Dowling, Fighting Infection (Harvard University Press, 1977.
[3]A Critical Look at Animal Research (Medical Research Modernization Committee, New York, 1990).
Antibiotics.
Particular animals, i.e., guinea pigs and hamsters, are especially sensitive to the negative effects of anti-biotic treatment. Ampicillin, Amoxycillin and Oxytetracycline are anti- biotics widely used by human beings but they are deemed 'toxic' and therefore inappropriate for guinea pigs and hamsters.[1] In the case of the Erythromycin, the usual human dose will kill a hamster.[2]
In Drug Development: From Laboratory to Clinic, Dr Walter Sneader noted that if guinea pigs had been used when penicillin was first tested, this valuable treatment would have almost certainly been abandoned as these animals are hypersensitive to penicillin. Florey, one of the scientists who carried out animal testing after Fleming's discovery of penicillin , admitted: 'If we had used guinea pigs exclusively, we should have said that pencillin was toxic, and we probably should not have proceeded to try and overcome the difficulties of producing the substance for...man'.[3] Thus, this is yet another example of how different animals provide different results in testing, and once again shows that the use of animals can, and does, impede medical progress.
[1]A. A. Tuffery (ed.), Laboratory Animals - An Introduction for New Experimenters, (Wiley, 1987).
[2]A single minimum recommended dose of erythromycin is 250-500mg every 6 hours, i.e., 3.5-7.0 mg/kg for a 70kg person. The lethal dose for hamsters is 3.5mg/kg.
[3]H. Florey, Conquest, January 1953.
Cancer.
In the first decade of the last century, epidemiology had identified a number of causes of cancer.[1] One of the earliest observations was that of Potts, an English surgeon who in the eighteenth century identified soot as a carcinogen in chimney sweeps. However, attempts to replicate his findings in animals failed,[2] although in 1918 researchers in Japan announced that cancer could be produced - on the ear of a rabbit by continually painting it with tar.
Progress was delayed by a dependence upon animals: the British epidemiologist Sir Richard Doll observes that human observational data was often dismissed because it was felt that success would be found in the laboratory.[1] When studies correctly reported that people who consumed high large amounts of fruit and vegetable were less likely to develop cancer,[3] little attention was given.[1]
Due to the lack of human epidemiological data, erroneous ideas arising from animal experimentation abounded; although only 5% of Western cancers are connected to viral infections,[4], e.g., some scientists believed that most, possibly all cases, were caused by viruses, an idea which arose from animal testing. One animal researcher even claimed that women should not breast feed their babies because, as in mice, a virus caused breast cancer which could be acquired in the mother's milk.[5]
After the Second World War, there was a greater interest in epidemiology with the realization that smoking caused lung cancer. In the years following there has been a greater awareness that the vast majority of instances of cancer can be prevented. Noteworthy is the 1980 US Congress Office of Technology Assessment Report on the causes of cancer which relied more far more on epidemiology than laboratory testing as these 'cannot provide reliable risk assessment'.[4]
Sadly, the curse of cancer is still very much with us and is likely to continue as long as animal experimentation is used in attempts to find the solution.
[1]R. Doll, Cancer, 1980, vol. 45, pp.2475-2485.
[2]W. H. Woglom, Archives of Pathology, 1926, vol. 2, pp.533-576.
[3]P. Stocks and M. N. Karn, Annals of Eugenics, 1933, vol. 5, pp.237-280.
[4]R. Peto and R. Doll, The Causes of Cancer (OUP, 1981).
[5]J. Furth, Bulletin of the New York Academy of Medicine, 1964, vol. 40, pp.421-431.
Opren.
Opren (Oraflex in America), to treat arthritis, was withdrawn in August 1982 after reports of deaths and serious liver damage after people had used the drug.[1] Since 1980, when it first appeared in the UK, there were some 3,500 reports of adverse effects with 61 deaths, mainly involving the elderly.[2]
Researchers declared Opren was a drug where the injuries could not be predicted from animal experimentation,[3] and Dista, which marketed Opren in Britain acknowledged that after Opren was studied for a year using rhesus monkeys, 'there were no apparent adverse effects on survival'.
[1]E. M. B. Sorensen, Toxicology Letters, 1986, vol. 34, pp.277-286.
[2]British Medical Journal, 14 August 1982, pp.459- 460.
[3]C. T. Eason, et al, Regulatory Toxicology and Pharmacology, 190, vol. 11, pp.288-307.
Stroke treatment.
Experimentation on rabbits, dogs, gerbils and monkeys suggested that the use of barbiturates could offer protection against the effects of a stroke,[1] and yet in humans, barbiturates were found to offer little or no protection.[2] In fact between 1978 and 1988, some 25 drugs which were found to be useful in treating animals with artificially-induced stokes did not come into general use.[2]
Some researchers have argued that an over-reliance on animal models may impede progress in treating the disease,[2] and Mayo Clinic researchers also acknowledged 'the answers to many of our questions regarding the underlying pathophysiology and treatment of stroke do not lie with continued attempt to model the human situation perfectly in animals, but rather with the development of techniques to enable the study of...living humans'.[2]
[1]Stroke, vol. 6, pp.28-33, 1974, vol. 5, pp.107, 1972, vol. 3, pp.726-732, Neurology, 1975, vol. 425, pp.870-874, Annals of Neurology, 1979, vol. 5, pp.59-64.
[2]D. O. Wiebers, et al, Stroke, 1990, vol. 21, pp.1-3.
Omeprazole.
A new test, developed by Glaxo, raised concerns about Omeprazole, an ulcer treatment produced by Astra, in respect of causing stomach cancer. The test involves dosing rats with a drug/substance and then removing tissue which is analysed for effects on the DNA. Interference with DNA is deemed to be a possible first step to cancer.
The test showed that Omeprazole damaged the DNA while it also showed that Ranitidine (Zantac), Glaxo's own anti-ulcer drug, did not.[1] Because of the test result, Glaxo ended the comparative trials of Ranititide and Omeprazole which the Lancet commented would almost certainly affect prescription.[2]
Astra responded by claiming that Glaxo's testing method was 'scientifically unsound' and the results had 'no clinical consequences'.[3] Astra went on to say that its own tests showed that after administering Omeprazole to rats for up to 2 years, to mice for 18 months, and to dogs for 12 months, there was 'no evidence for a direct carcinogenic potential in the stomach or elsewhere' - the very opposite of Glaxo's conclusion after its animal testing.
[1]B. Burlinson, et al, Lancet, 17 February 1990, p.419.
[2]Lancet, 17 February 1990, p.386.
[3]L. Ekman, et al, Lancet, 17 February 1990, pp.419- 420.
Encainide and Flecainide.
A study conducted in America discovered that two drugs which were designed to prevent irregular heart beats could cause certain types of patients to have heart attacks. CAST (Cardiac Arrhythmia Suppression Trial) commenced in 1987 but was concluded within two years after physicians discovered that more deaths occurred in those patients using encainide and flecainide than those who received a placebo (a dummy pill).[1]
These findings led to estimates that nationally, some 3000 people may have prematurely died after using these drugs,[2] and yet animal testing had indicated that encainide and flecainide were safe and effective.[3]
[1]CAST Investigators, New England Journal of Medicine, 10 August 1989, pp.406-412.
[2]Dr. J. Morganroth reported in Washingon Times, 26 July 1989.
[3]Flecainide: B. Holmes and R. C. Heel, Drugs, 1985, vol. 29, pp.1-33. Encainide: D. C. Harrison, et al, American Heart Journal, 1980, vol. 1090, pp.1046-1054, and J. E. Byrne et al, Journal of Pharmacology and Experimental Therapeutics, 1977, vol. 200, pp.147-154.
Olive Oil.
Olive oil has been used without any noticeable ill-effect on the human body for thousands of years.[1] And yet testing undertaken at New York University showed that olive oil had a harmful effect when it was applied to the skin of rats, e.g., swelling.[2]
[1]M. M. Rieger and G. W. Battista, Journal of the Society of Cosmetic chemists, 1964, vol. 15, pp.161-172.
[2]E. O. Butcher, Journal of Investigative Dermatology, 1951, vol. 16, pp.85-90.
Skin tests.
Rabbits and guinea-pigs are frequently used in respect of assessing irritancy; this is despite the fact that these animals do not provide accurate results. For example, animal experiments indicate that hypochlorite bleach is safe for human usage as it only results in 'slight visible irritation' in rabbits and guinea pigs.[1] In reality, in humans, it causes severe skin reactions.
[1]G. A. Nixon, et al, Toxicology and Applied Pharmacology, 1975, vol. 31, pp.481-490.
Cancer and smoking.
In 1954, the results of an investigation into smoking was published; this showed that the likelihood of developing lung cancer increased in accordance with the number of cigarettes which were smoked.[1] By this time, a number of other reports had also been published asserting much the same thing. However researchers continued to argue that claiming lung cancer and smoking were linked was unwarranted due to the disease not being produced in laboratory animals.[2]
In 1956, the British Empire Cancer Campaign (the forerunner to the Cancer Research Campaign) advised that during two years of experimentation with mice, rabbits and other animals which involved them being exposed to tobacco derivatives by inhalation, feeding, injection and skin painting, none had developed cancer.[3]
Consequently, due to the negative results of the animal experimentation, health warnings about the dangers of smoking were delayed for several years: further experimentation showed that it was either difficult or impossible to induce lung cancer in animals using the inhalation method.[4]
[1]R. Doll and A. B. Hill, British Medical Journal, 26 June 1954, pp.1451-1455.
[2]Reported in S. Peller, Quantitative Research in Human Biology (J. Wright and Sons, 1967).
[3]Reported in E. Northrup, Science Looks at Smoking (Conrad-McCann, 1957).
[4]Lancet, 25 June 1977, pp.1348-1349. See also F. T. Gross, et al, Health Physics, 1989, vol. 56, p.256.
Asbestosis.
In 1907, the lung disease asbestosis (caused by breathing in asbestos) was recognised. Although research into this condition, using animals, commenced in 1925, most of the results were contradictory. For example, in 1930 on the basis of the animal testing conducted, researchers designated the chrysotile, amosite and crocidolite forms of asbestos as harmless .[1] And yet others determined that while chrysotile caused lung damage in guinea pigs, it did not do so in rabbits.[2]
Researchers using animals then reported that injuries caused by asbestos began to heal when the animals were removed from the asbestos-dust environment.[2] This is in stark contrast to humans when asbestosis advances even after the person is no longer exposed. It was only later that animal researchers were able to mimic this feature in animals.[3]
Concern grew when it was announced that there was a link between asbestos and lung cancer, and yet attempts to induce cancer in animals were unsuccessful. Because of this, even though there was considerable evidence of the link from asbestos workers, there was doubt about the carcinogenic effect of asbestos until the 1960s.[4,5] It was only then that researchers could mimic the condition in animals.
The Annals of the New York Academy of Sciences says that before this: 'a large literature on experimental studies has failed to furnish any definite evidence for induction of malignant tumours in animals exposed to various varieties and preparations of asbestos'.[6]
[1]Reported in L. U. Gardner, Journal of the American Medical Association, 19 November 1938, pp.1925-1936.
[2]J. C. Wagner, British Journal of Industrial Medicine, 1963, vol. 20, pp.1-12. [3]J. C. Wagner, et al, British Journal of Cancer, 1974, vol. 29,. pp.252-269.
[4]P. E. Enterline in Epidemiology and Health Risk Assessment, ed. L. Gordis (OUP, 1988).
[5]P. E. Enterline. American Review of Respiratory Diseases, 1978, vol. 118, pp.975-978.
[6]W. E. Smith, et al, Annals of the New York Academy of Sciences, 1965, vol. 132, pp.456-488.
Ibufenac.
This anti-inflammatory medication became available in Britain during the mid-1960s but had to be withdrawn within two years after deaths occurred; the primary cause being liver damage.
This happened despite 'extensive' animal testing in which mice, rats and dogs were used; these showed no indication of liver damage (apart from a slight effect in rats exposed to a lethal dose).[1]
Dr M. F. Cuthbert of the British Department of Health and Social Security's Medicine Division admitted: 'Evidence of liver damage is sometimes detected in animal studies of non-steroidal anti- inflammatory drugs, but usually no such evidence is forthcoming even in circumstances when a drug is eventually shown to be hepatotoxic [liver-damaging] to man'.[1]
[1]M. F. Cuthbert, Current Approaches in Toxicology, ed. B. Ballantyne (Wright and Sons, 1977).
Fialuridine (FIAU).
Trials at America's National Institutes of Health of a new drug to combat hepatitis B were halted in the Summer of 1993 after complications and deaths occurred among those involved in the trials. Although fialuridine was supposed to improve the condition of persons suffering from liver disease, many of those who had prolonged treatment experienced a deterioration in their health; some died from liver failure.[1]
And yet the drug was found to be safe in animal experiments,[1] reducing the amount of the virus in the preferred animal model used; tests for toxicity were also conducted in mice, rats and rhesus monkeys. Indeed one of the principal investigators asked: 'Why didn't the animal toxicity studies show any abnormality at all due to the drug?'.[2]
In fact the metabolism of anti-viral drugs is considered to be very different in animals and humans.[3].
[1]N. Touchette, The Journal of NIH Research, 1993. 5, pp.33-55.
[2]J. Hoofnagle, reported in [1].
[3]C. Macilwain, Nature, 22 July 1993, p.275.
Hytrin (Abbott Laboratories Ltd)
Containing terazosin as terazosin hydrochloride.
Use: Hytrin is indicated in the treatment of mild to moderate hypertension.
Contra-indications, warnings etc: Carcinogenicity: Hytrin has been shown to produce tumours in male rats when administered at a high dose over a long period of time. No such occurrences were seem in a similar study in mice. The relevance of these findings with respect to the clinical use of the drug in man is unknown.
Losec (Astra Pharmaceuticals Ltd)
Contains omeprazole as enteric-coated granules.
Use: Treatment of reflux oesophagitis. Treatment of duodenal and benign gastric ulcers including those complicating NSAID therapy.
Contra-indications, warnings, etc: Animal toxicology: Gastric ECL-cell hyperplasia and carcinoids, localised to the oxyntic mucosa, have been observed in life-long studies in rats. These changes have been related to sustained hypergastrinaemia secondary to acid inhibition, and not from a direct effect of any individual drug. No treatment related mucosal changes have been observed in patients treated continuously for periods up to 5 years.
Dtic-dome (Bayer plc)
Active ingredient: 5-(3,3-dimethyl-1-triazeno) imidazole-4-carboxamide prepared as the citrate salt (dacarbazine).
Use: metastatic malignant melanoma, sarcoma, Hodgkin's disease.
Contra-indications, warnings, etc: Studies have demonstrated this agent to have a carcinogenic and teratogenic effect when used on animals.
Ridaura Tiltab tablets (Bencard)
Containing 3 mg auranofin.
Use: In the management of adults with active progressive rheumatoid arthritis only when non-steroidal anti-inflammatory drugs have been found to be inadequate alone to control the disease, i.e. when second-line therapy is required.
Contra-indications, warnings, etc: Gold has been shown to be carcinogenic in rodents although there was no evidence of carcinogenicity in 7 year dog studies.
Bezalip (Boehringer Mannheim UK (Pharmaceuticals) Ltd)
Contains bezafibrate.
Use: In hyperlipidaemias of Type 11a, 11b, 111, 1V and V.
Contra-indications, warnings, etc: Warnings: The chronic administration of a high dose of bezafibrate to rats was associated with hepatic tumour formation in females. This dosage was in the order of 30 to 40 times the human dosage. No such effect was apparent at reduced intake levels approximating more closely to the lipid-lowering dosage in humans.
(Author's note: Drug companies often excuse animal results by claiming that the dosage used in animal tests was far higher than that used in human beings. If such studies are irrelevant because of the high dosage then why do them?)
Spiroctan (Boehringer Mannheim UK)
Contains spironolactone
Use: Spiroctan is recommended for the treatment of congestive cardiac failure, cirrhosis with ascites and oedema, malignant ascites, nephrotic syndrome and also for diagnosis and treatment of primary hyperaldosteronism.
Contra-indications, warnings, etc: Carcinogenicity: Spironolactone has been shown to produce tumours in rats when administered at high doses over a long period of time. The significance of these findings with respect to clinical use is not certain.
Bicnu (Bristol-Myers Pharmaceuticals)
Contains a 30 ml vial containing 100 mg carmustine and a 5 ml vial containing 3 ml sterile ethanol diluent.
Use: BiCNU is indicated as palliative therapy as a single agent or in established combination therapy with other approved chemotherapeutic agents in the following:
1. Brain tumours - Glioblastoma, brainstem glioma, medulloblastoma, astrocytoma, ependymoma, and metastatic brain tumours.
2. Multiple myeloma - in combination with prednisone.
3. Hodgkin's Disease - As secondary therapy in combination with other approved drugs in patients who relapse while being treated with primary therapy, or who fail to respond to primary therapy.
4. Non-Hodgkin's lymphomas - As secondary therapy as above.
Contra-indications, warnings, etc: BiCNU is carcinogenic in rats and mice, producing a marked increase in tumour incidence in doses approximating those employed clinically.
Apresoline (Ciba Laboratories)
Contains Hydralazine Hydrochloride.
Use: Hypertension
Contra-indications, warnings etc: Warnings: Hydralazine, in lifetime carcinogenicity studies, caused, towards the end of the experiments, small but statistically significant increases in lung tumours in mice and in hepatic and testicular tumours in rats. These tumours also occur spontaneously with fairly high frequency in aged rodents.
With due consideration of these animal and in-vitro toxicological findings, hydralazine in therapeutic doses does not appear to bear a risk that would necessitate a limitation of its administration. Many years of clinical experience have not suggested that human cancer is associated with hydralazine use.
Tolectin 200/400 Mg capsules (Cilag Ltd)
Contains tolmetin sodium dihydrate.
Use: Rheumatoid arthritis,; osteoarthritis; ankylosing spondylitis; peri-articular disorders such as fibrositis and bursitis.
Contra-indications, warnings, etc: Renal papillary necrosis has occurred in animals after long term administration although there has been no evidence of renal toxicity in clinical trials.
Chendol 125, and Chendol 250 (CP Pharmaceuticals)
Contains chenodeoxycholic acid.
Use: For dissolution of radiolucent cholesterol-rich gallstones in functioning gall bladders. It has a particular place where surgery is contra-indicated or those patients anxious to avoid surgery.
Contra-indications, warnings, etc: Precautions: Chenodeoxycholic acid, given in long term studies at doses of 600 mg/kg/day to rats and 1000 mg/kg/day to mice, induced malignant liver cell tumours in female rats and male mice. The clinical significance of these findings is not known.
Normax (Evans Medical Ltd)
Contains danthron docusate sodium.
Use: Constipation in geriatric practice. Analgesic-induced constipation in terminally ill patients of all ages. Constipation in cardiac failure and coronary thrombosis (conditions in which defaecation must be free of strain).
Contra-indications, warnings, etc: Precautions: In experimental animals, danthron has been associated with adenocarcinomas in the bowel and tumours in the liver.
Farlutal (Farmitalia Carlo Erba Ltd)
Contains medroxyprogesterone acetate.
Use: Palliative treatment of hormone-sensitive malignancies. Farlutal has been successfully used to produce regressions in breast, endometrial, prostatic and renal cell carcinoma.
Contra-indications, warnings, etc: Precautions: It should be noted that long term administration of medroxyprogesterone acetate to beagle dogs has resulted in the development of mammary nodules which were occasionally found to be malignant. The relevance of these findings to humans has, however, not been established.
Pharmorubicin rapid dissolution (Farmitalia Carlo Erba Ltd)
Contains epirubicin hydrochloride with lactose and hydroxybenzoate.
Use: Antimitotic and cytotoxic.
Contra-indications, warnings, etc: Like most other anticancer agents, epirubicin has shown mutagenic and carcinogenic properties in animals.
Zavedos (Farmitalia Carlo Erba Ltd)
Contains idarubicin hydrochloride with lactose.
Use: Antimitotic and cytotoxic agent.
Contra-indications, warnings, etc: Warnings: Like most other cytotoxic agents, idarubicin has mutagenic properties and it is carcinogenic in rats.
Tegretol (Geigy Pharmaceutical)
Active ingredient: Carbamazepine.
Use: Epilepsy generalised tonic-clonic and partial seizures.
Contra-indications, warnings, etc: Precautions: In rats treated with carbamazepine for two years, the incidence of tumours of the liver was found to be increased. There is, however, no evidence to indicate that this observation has any significant bearing on the therapeutic use of the drug.
Grisovin tablets (Glaxo Laboratories Ltd)
Contain griseofulvin.
Use: The treatment of fungal infections of the skin, scalp, hair or nails where topical therapy is considered inappropriate or has failed.
Contra-indications, warnings etc: Precautions: Long term administration of high doses of griseofulvin with food has been reported to induce hepatomas in mice and thyroid tumours in rats but not hamsters. The clinical significance of these findings is not known.
Lasilactone capsules (Hoechst)
Contain Frusemide and Spironolactone.
Use: In the treatment of resistant oedema where this is associated with secondary hyperaldosteronism; conditions include chronic congestive cardiac failure and hepatic cirrhosis.
Contra-indications, warnings, etc: Carcinogenicity: Spironolactone has been shown to produce tumours in rats when administered at high doses over a long period of time. The significance of these findings with respect to clinical use is not c
ertain.
Atromid (ICI Pharmaceuticals)
Contains Clofibrate.
Use: In the treatment of severe hyperlipoproteinaemia where full investigation has been performed to define the abnormality.
Contra-indications, warnings, etc: Clofibrate has been shown to produce liver tumours in rats and mice. The liver changes found in rodents have not been seen in other species, including sub-human primates and man. The relevance of this finding to man has not been established.
Nolvadex, Nolvadex - D, and Nolvadex - Forte tablets (ICI Pharmaceuticals)
Containing Tamoxifen Citrate.
Use: The treatment of breast cancer and the treatment of anovulatory infertility.
Contra-indications, warnings, etc: Gonadal tumours in mice and liver tumours in rats receiving tamoxifen have been reported in long-term studies. The clinical relevance of these findings has not been established.
Zoladex (ICI Pharmaceuticals)
Containing goserelin acetate.
Use:
1. Prostate cancer.
2. Advanced breast cancer in pre- and peri-menopausal women suitable for hormonal manipulation.
3. Endometriosis.
Contra-indications, warnings, etc: General: Following long-term repeated dosing with Zoladex, an increased incidence of benign pituitary tumours has been observed in male rats. Whilst this finding is similar to that previously noted in this species following surgical castration, any relevance to man has not been established.
In mice, long term repeated dosing with multiples of the human dose produced histological changes in some regions of the digestive system manifested by pancreatic islet cell hyperplasia and a benign proliferative condition in the pyloric region of the stomach, also reported as a spontaneous lesion in this species. The clinical relevance of these findings is unknown.
Novantrone injection (Lederle Laboratories)
Contains mitozantrone hydrochloride.
Use: For the treatment of advanced breast cancer, non-Hodgkin's lymphoma and adult acute non-lymphocytic leukaemia. Novantrone has also been used in the palliation of non-resectable primary hepatocellular carcinoma.
Contra-indications, warnings, etc: Warnings: Novantrone is mutagenic in vitro and in vivo in the rat. In the same species there was a possible association between administration of the drug and development of malignant neoplasia. The carcinogenic potential in man is unknown.
Prostap SR (Lederle Laboratories)
Contains leuprorelin acetate.
Use: In the treatment of advanced prostatic cancer and the management of endometriosis, including pain relief and reduction of endometriotic lesions.
Contra-indications, warnings, etc: Warnings: Men: Whilst the development pituitary adenomas has been noted in chronic toxicity studies at high doses in some animal species, this has not been observed in long term clinical studies with Prostap.
Thiotepa (Lederle Laboratories)
Contains Thiotepa (N,N',N'' triethylenethiophosphoramide)
Use: A polyfunctional alkylating agent used alone or in combination with other cytotoxic drugs, hormones, radiotherapy or surgery in the treatment of neoplastic diseases.
Contra-indications, warnings, etc: Thiotepa has been reported to possess mutagenic activity on the basis of bacterial, plant and mammalian mutagenicity tests. It has also been reported to be carcinogenic in mice and rats. These effects are consistent with its activity as an alkylating agent. The carcinogenic potential in humans has not been clearly established.
Celace (Eli Lilly and Co Ltd)
Contains pergolide base.
Use: Adjunctive treatment to levodopa in the management of the signs and symptoms of Parkinson's disease.
Contra-indications, warnings, etc: Carcinogenesis, mutagenesis and impairment of fertility: Two year carcinogenicity studies in mice and rats used doses up to 340 and 12 times the maximum human oral dose (6 mg or 6000 micrograms/day equivalent to 120 micrograms/kg/day). A low incidence of uterine neoplasms occurred in both rats and mice. Endometrial adenomas and carcinomas were observed in rats. Endometrial sarcomas were observed in mice. These occurrences are probably attributable to the high oestrogen/progesterone ratio, which would occur in rodents as a result of the prolactin-inhibiting action of pergolide mesylate.
These endocrine mechanisms are not present in humans. However, there are no human data with pergolide to substantiate this conclusion concerning the lack of potential for human risk.
Mutagenic potential was evaluated in a battery of tests. A weak response was noted in one test but the other 3 tests were negative. The relevance to humans is unknown.
Seconal Sodium (Eli Lilly and Co Ltd)
Contains Secobarbitone Sodium.
Use: For the short-term treatment of severe, intractable insomnia.
Contra-indications, warnings, etc Carcinogenesis: Animal data show that phenobarbitone can be carcinogenic after lifetime administration.
Sodium Amytal Injections (Eli Lilly and Co Ltd)
Contains Amylobarbitone Sodium.
Use: May be used parenterally to control status epilepticus, but it is not the barbiturate of choice in the routine treatment of grand mal epilepsy.
Contra-indications, warnings, etc: Carcinogenesis: Animal data show that phenobarbitone can be carcinogenic after lifetime administration.
Destolit (Marion Merrell Dow Ltd)
Contains ursodeoxycholic acid.
Use: For the dissolution of radiolucent (i.e. non-radio opaque) cholesterol gallstones in patients with a functioning gallbladder.
Contra-indications, warnings, etc: A product of this class has been found to be carcinogenic in animals. The relevance of these findings to the clinical use of ursodeoxycholic acid has not been established.
Sabril tablets (Marion Merrell Dow Ltd)
Contains vigabatrin.
Use: For the treatment of epilepsy which is not satisfactorily controlled by other antiepileptic drugs.
Contra-indications, warnings, etc: Warning: Animal safety studies indicate that vigabatrin causes intramyelinic oedema in the brain white matter tracts. Currently there is no evidence to suggest that this effect occurs in man.
Dolobid (Thomas Morson Pharmaceuticals)
Contains Diflunisal.
Use: For the relief of pain and also inflammation associated with osteoarthritis and rheumatoid arthritis.
Contra-indications, warnings, etc: Precautions: In rats and dogs, high oral doses of diflunisal (50-200 mg/kg/day) as with aspirin, produced similar pathological changes (gastro-intestinal ulceration and renal papillary oedema). These dosages are approximately 3 to 12 times the maximum dosages recommended in man.
Ortho dienoestrol cream (Ortho)
Contains Dienoestrol.
Use: Atrophic vaginitis and kraurosis vulvae in post menopausal women, and for the treatment of pruritus vulvae and dyspareunia when associated with the atrophic vaginal epithelium.
Contra-indications, warnings, etc: Long term continuous administration of natural and synthetic oestrogens in certain animal species increases the frequency of carcinomas of the breast, cervix, vagina and liver. There is now evidence that oestrogens increase the risk of carcinoma of the endometrium in humans.
At the present time there is no satisfactory evidence that oestrogens given to post-menopausal women increase the risk of cancer of the breast, although a recent long-term follow up of a single physician has raised this possibility. However, because of animal data there is a need for caution in prescribing oestrogens for women with a strong family history of breast cancer or who have breast nodules, fibrocystic disease, or abnormal mammograms.
(Author's Note: Do oestrogens only increase the risk of cancer in female animals who have a strong family history of breast cancer, or who have breast nodules, fibrocystic disease or abnormal mammograms?).
Retin-a Lotion, Gel, Cream (Ortho)
Contains Tretinoin.
Use: For topical application in the treatment of acne vulgaris in which comedones, papules and pustules predominate.
Contra-indications, warnings, etc: Recent studies in mice treated with the active ingredient (tretinoin) of Retin-A and exposed to artificial sunlight suggest that tretinoin may speed up the appearance of sunlight induced skin tumours. Laboratory mice treated with tretinoin but not exposed to sunlight did not develop skin tumours. The significance of these studies as related to human beings is unknown. High oral doses of tretinoin (retinoic acid), like Vitamin A, are teratogenic in animals.
Lopid (Parke-Davis Research Laboratories)
Contains gemfibrozil and polysorbate 80 PhEur.
Use: For the primary prevention of coronary heart disease in men between 40-55 years of age and with hyperlipidaemias who have not responded to diet and other appropriate measures.
Contra-indications, warnings, etc: Precautions: Long-term toxicity studies in rats and mice were carried out at one and ten times the human dose on a weight for weight basis. In male rats receiving ten times the human dose, there was a significant increase in incidence of benign liver nodules and liver carcinomas. Male rats receiving a dose equivalent to the human dose had no statistically significant increase in the incidence of liver carcinomas. At all dose levels, there were no statistically significant differences from controls in the incidence of liver tumours in female rats, or in mice of either sex.
Electron microscopy demonstrated a marked hepatic peroxisome proliferation following Lopid administration to the male rat. Similar changes have been sought but not found in the human liver at up to 27 months continuous gemfibrozil therapy. Male rats had a dose-related increase of benign Leydig cell tumours. Subcapsular bilateral cataracts occurred in 10%, and unilateral cataracts in 6.3% of the high dose males.
Mithracin (Pfizer Ltd)
Contains plicamycin, mannitol and disodium phosphate.
Use: For the treatment of refractory hypercalcaemia associated with a variety of neoplasms.
Contra-indications, warnings, etc: Warnings: Antineoplastic and cytotoxic agents have been shown to be mutagenic and carcinogenic in animals and possibly man.
Only limited animal and in vitro mutagenicity studies have been carried out with plicamycin; the possibility that plicamycin has similar effects to other antineoplastic cytotoxic agents should be borne in mind.
Calcitare (Rhone-Poulenc Rorer Ltd)
Contains Calcitonin (Pork).
Use: For short term treatment in:
i) Paget's disease of bone
ii) Hypercalcaemia.
Contra-indications, warnings, etc: A species and strain-specific dose-related increase of pituitary adenomas has been observed in long term toxicity studies in the rat. As the significance of these findings to man is uncertain, long term use is not recommended.
Calsynar (Rhone-Poulenc Rorer Ltd)
Contains synthetic Salmon Chloride. The solution also contains Sodium Chloride, Sodium Acetate, Acetic Acid and Phenol.
Use: For the short term treatment of:
a) Paget's disease of bone.
b) Advancing osteolytic hypercalcaemia of malignancy.
c) Pain associated with advanced metastatic bone cancer.
d) Postmenopausal osteoporosis.
Contra-indications, warnings, etc: Precautions: Rat carcinogenicity studies have shown a dose related excess of pituitary tumours. As the significance of this finding is uncertain, long term use is not recommended.
Roaccutane (Roche Products Ltd)
Contains isotretinoin.
Use: For the treatment of cystic and conglobate acne and severe acne which has failed to respond to an adequate course of a systemic antimicrobial agent.
Contra-indications, warnings, etc: Precautions: At the completion of a lifespan study in rats there was an increased incidence of phaeochromocytoma in animals given isotretinoin at dosages of 32 and 8 mg/kg/day, but not 2 mg/kg/day. Since rats are particularly prone to develop this tumour type, the significance of this finding for use of Roaccutane in man is uncertain; nevertheless, repeated courses of treatment are not normally recommended.
Negram (Sanofi Winthrop)
Contains Nalidixic Acid.
Use: For the treatment of acute or chronic infections.
Contra-indications, warnings, etc: Nalidixic acid has been shown to induce lesions in weight-bearing joints of young animals. The relevance of this to man is unknown.
Androcur (Schering Health Care)
Contains cyproterone acetate.
Use: Control of libido in severe hypersexuality and/or sexual deviation in the adult male.
Contra-indications, warnings, etc: Warnings/side-effects: Cyproterone acetate has been found to cause liver abnormalities in animals, including the development of tumours.
Cyprostat (Schering Health Care)
Contains cyproterone acetate.
Use: Palliative treatment of prostatic carcinoma.
Contra-indications, warnings, etc: Cyproterone acetate has been found to cause liver abnormalities in animals, including the development of tumours.
Dianette (Schering Health Care)
Contains anti-androgen cyproterone acetate and oestrogen ethinyloestradiol.
Use: In women only: (i)severe acne, refractory to prolonged oral antibiotic therapy and (ii)idiopathic hirsutism of mild to moderate degree.
Contra-indications, warnings, etc: Warnings: Like many other steroids, cyproterone acetate, when given in very high doses and for the majority of the animal's life-span, has been found to cause an increase in the incidence of tumours, including carcinoma, in the liver of rats. The relevance of this finding to humans is unknown. Dianette has been shown to have good liver tolerance in women given prolonged treatment.
Aldactide (Searle)
Contains Spironolactone and Hydroflumethiazide.
Use: Congestive cardiac failure.
Contra-indications, warnings, etc - Warnings: Carcinogenicity: Spironolactone has been shown to produce tumours in rats when administered at high doses over a long period of time. The significance of these findings with respect to clinical use is not certain.
Cytotec (Searle)
Contains misprostol
Use: for the healing of duodenal ulcer and gastric ulcer including those induced by non steroidal anti inflammatory drugs (NSAID) in arthritic patients at risk, whilst continuing their NSAID therapy.
Further information: Cytotec in multiples of the recommended therapeutic dose in animals has produced gastric mucosal hyperplasia. This characteristic response of E prostaglandins reverts to normal on discontinuation of the compound. In patients, histological examination of gastric biopsies taken before and after treatment with misoprostol after up to one year's duration have shown no adverse tissue response attributable to misoprostol.
Napratec (Searle)
Contains Naproxen and Cytotec (containing misoprostol)
Uses: Naproxen is indicated for the treatment of rheumatoid arthritis, osteoarthritis (degenerative arthritis) and ankylosing spondylitis. Cytotec is indicated for the prophylaxis of nonsteroidal anti-inflammatory drug induced gastroduodenal ulceration.
Further information: Cytotec in multiples of the recommended therapeutic dose in animals has produced gastric mucosal hyperplasia. This characteristic response of E prostaglandins reverts to normal on discontinuation of the compound. In patients, histological examination of gastric biopsies taken before and after treatment with misoprostol after up to one year's duration have shown no adverse tissue response attributable to misoprostol.
Dolmatil tablets (E. R. Squibb and Sons Ltd)
Contains sulpiride (and hydrated silica, lactose, magnesium stearate, methyl cellulose, potato starch, talc).
Use: Acute and chronic schizophrenia.
Contra-indications, warnings, etc: Warnings: In long term animal studies with neuroleptic drugs, including sulpiride, an increased incidence of various endocrine tumours (some of which have occasionally been malignant) has been seen in some but not all strains of rats and mice studied. The significance of these findings to man is not known; there is no evidence of an association between Dolmatil use and tumour risk in man.
Chenofalk (Thames Laboratories Ltd)
Contains chenodeoxycholic acid (CDCA). (And gluten).
Use: Dissolution of radiolucent gallstones measuring up to 15 mm diameter.
Contra-indications, warnings, etc: Warnings: Chenodeoxycholic acid given in long-term studies at doses of 600 mg/kg/day to rats and 1000 mg/kg/day to mice, induced malignant liver cell tumours in female rats and benign liver cell tumours in female rats and male mice. The clinical significance of these findings is not known.
Ursofalk (Thames Laboratories Ltd)
Contains ursodeoxycholic acid (UDCA) and gluten.
Use: Dissolution of radiolucent gallstones measuring up to 15 mm diameter.
Contra-indications, warnings, etc: A product of this class has been found to be carcinogenic in animals. The relevance of these findings to the clinical use of UDCA has not been established.
Sulpitil (Tillotts Laboratories)
Contains sulpiride.
Use: For the treatment of acute and chronic schizophrenia.
Contra-indications, warnings, etc: Warnings and precautions: In long term animal studies with neuroleptic drugs, including sulpiride, an increased incidence of various endocrine tumours, some of which have occasionally been malignant, has been seen in some, but not all, strains of rats and mice studied. The significance of these findings to man is not known. There is no current evidence of an association between neuroleptic use and tumour risk in man.
Depo-Provera (Upjohn Ltd)
Contains medroxyprogesterone acetate.
Use: Progestogen: for the treatment of endometriosis.
Contra-indications, warnings, etc: Warnings, precautions, side-effects: Endometrial tumours have developed in monkeys given fifty times the human contraceptive dose but the relevance of this to man has not been established.
Hemabate Sterile Solution (Upjohn Ltd)
Contains carboprost as the tromethamine salt.
Use: Treatment of post-partum haemorrhage due to uterine atony and refractory to conventional methods of treatment with oxytocic agents and ergometrine used either alone or in combination.
Contra-indications, warnings, etc: Precautions: Animal studies lasting several weeks at high doses have shown that prostaglandins of the E and F series can induce proliferation of bone.
Prostin E2 (Upjohn Ltd)
Contains dinoprostone.
Use: Oxytocic agent.
For the induction of labour when there are no foetal or maternal contra-indications.
Contra-indications, warnings, etc: Precautions: Animal studies lasting several weeks at high doses have shown that prostaglandins of the E and F series can induce proliferation of bone.
Myleran tablets (Wellcome Medical Division)
Contains Busulphan.
Use: For the palliative treatment of the chronic phase of chronic granulocytic leukaemia.
Contra-indications, warnings, etc: Precautions: Busulphan has been shown to be mutagenic in various systems, including bacteria, fungi, Drosophila and cultured mouse lymphoma cells. In vivo cytogenetic studies in rodents have shown an increased incidence of chromosome abberations in both germ cells and somatic cells after busulphan treatment.
NB. Busulphan interferes with spermatogenesis in experimental animals.
Retrovir capsules and syrup (Wellcome Medical Division)
Contains zidovudine.
Use: For the management of patients with advanced HIV disease.
Contra-indications, warnings, etc: Mutagenicity: Zidovudine was weakly mutagenic in a mouse lymphoma cell assay and was positive in an in vitro cell transformation assay. Clastogenic effects (chromosome damage) were observed in an in vitro study in human lymphocytes and in in- vivo oral repeat dose micronucleus studies in rats and mice. An in vivo cytogenetic study in rats did not show chromosomal damage. The clinical significance of these findings is unclear.
Carcinogenicity: Zidovudine was administered orally at three dosage levels to separate groups of mice and rats (60 females and 60 males in each group). Initial single daily doses were 30, 60 and 120 mg/kg/day and 80, 220 and 600 mg/kg/day in mice and rats respectively. The doses in mice were reduced to 20, 30 and 40 mg/kg/day after Day 90 because of treatment-related anaemia, whereas in rats only the high dose was reduced (to 450 and then 300 mg/kg/day on Days 91 and 279, respectively).
In mice, seven late-appearing (after 19 months) vaginal neoplasms (5 squamous cell carcinomas, one squamous cell papilloma and one squamous cell polyp) occurred at the highest dose. One late-appearing squamous cell papilloma occurred in the vagina of a middle-dose animal. No vaginal tumours were found at the lowest dose.
In rats, two late-appearing (after 20 months) vaginal squamous cell carcinomas occurred in animals given the highest dose. No vaginal tumours occurred at the middle or low doses in rats.
The predictive value of rodent carcinogenicity studies for humans is uncertain and thus the clinical significance of these findings is unclear.
Author's Comments:
In addition to the general warnings I have recorded above there are many drug companies which warn doctors not to give specific products to patients who are pregnant. These companies invariably report having performed experiments on pregnant animals but then often go on to admit (something like): 'the relevance of these studies to human beings is not known'. It is difficult to avoid asking the question: 'Why do the studies if the relevance is not known?' As can be seen from the above, a huge number of drug companies seem to be doing animal tests without knowing their relevance to human patients.
On other occasions drug companies report that animal experiments have shown that their drugs cause problems - but that human experience suggests that the drug is entirely safe so the animal experiments can be safely ignored! Animal experiments provide answers for all seasons. It is not surprising that drug companies love them.
In some of the examples which follow drug companies seem uncertain about the significance of the animal experiments which have been done. If the relevance of the animal experiments is not known or the experiments cannot be relied upon then why on earth does anyone do them? Just as puzzling are the many instances where drug companies state that animal experiments have not indicated that there will be any problems if their drugs are given to pregnant women - but still advise doctors against giving those drugs to pregnant women.
These short sections are intended only to illustrate the point I want to make and are not intended to provide useful information about the drugs concerned.
Dr Vernon Coleman.
SOURCE: http://vivisection-absurd.org.uk/errors2.html