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A summer pastime
SHORT REVIEWS
33
plete the cycle of spermatogenesis, exposure of the male to the compound must exceed this period in order to avoid the development of spermatozoa which have not been exposed to the test substance. Space does not permit a detailed report of papers on metabolism and chemical pharmacology in relation to toxicity studies, nor of the interesting report, presented by R. Wien, of the "Study Group on the Importance of the Strains and Species of Animals used in Toxicity Tests". Suffice it to say that a great many keert and able minds are at last being brought to bear on long-neglected problems--a comforting thought.
A SUMMER PASTIME Each Spring brings the massive issue of Federation Proceedings to test the sense of dedication of the toxicologist. At least it does have a Subject Index. Not so the Annual Report of the British Empire Cancer Campaign for 1962, which comes just when the sun is shining and the garden beckons. Nevertheless, industrious scanning of its 700 pages proves rewarding (page numbers are inserted in brackets).
Inorganic agents Elsewhere in this issue (p. 107) we refer to subcutaneous tumours produced by injections of cadmium (Cd) pigments. Cd sulphate has also produced malignant tumours at the injection site in rats, as well as atrophy and tumours of the testis (pp. 34-5). The quantitative aspects are instructive. In rats as little as 2.2 mg Cd/kg given as a single dose sufficed to induce complete testicular atrophy within a few days; with 1.1 mg Cd/kg atrophy was incomplete. Elsewhere in the Report (p. 657) there is a further description of the testicular changes, which were recorded by Parizek (J. Reprod. Fertil. 1960, 1, 294) in five species. This raises the question: to what extent is man susceptible? Analysis of human testes (p. 82) revealed a range of Cd content from 0.48-2.28 ~g]g. This represents an approximate total of 19.2-91.2 ~tg for a 70-kg man. In view of the importance of possible Cd-zinc (Zn) antagonisms it is useful to note (p. 253) the number of tissue enzymes either containing firmly bound Zn or more or less specifically dependent on available Zn for maximal activity. It would be interesting, for instance, to follow the effects of Cd on the isoenzymes of the various Zn-containing dehydrogenases in the testis. The carcinogenic action of powdered metals when injected into rat muscle is exemplified by nickel and cobalt (pp. 355-7; 531). Copper, iron, tantalum and arsenic do not induce tumours under these conditions.
Envh'onmental and other factors Soil (p. 397), lubricating oil (pp. 35-6; 33), printing ink black (p. 33) and various paraffin and microcrystalline waxes (p. 33) have been studied for carcinogenicity. Results were negative, except that the lubricating oil showed a weak tumour-promoting effect. The earlierreported findings on eggs (p. 66 of this issue) contrast with the outcome of an experiment (pp. 504-5) in which chickens were maintained, from hatching to a healthy ripe old age, on a diet made up entirely of boiled eggs salted with manganese sulphate. After 1-3.5 yr no tumours developed and further experiments on eggs and egg fractions look likely to yield equally negative results.
34
SHORT REVIEWS
Organic compounds The work on lactones (pp. 158-9) is covered elsewhere in this Journal (p. 64). Further items of outstanding interest concern the metabolism of the bladder carcinogen, 2-naphthylamine (pp. 37--40) [which will be reported separately in the next issue of the Journal] and various approaches to the testing of compounds for potential carcinogenicity. Using the technique of implantation into the bladder of mice, pellets formed by compressing crushed paraffin wax with the test compound elicited more bladder carcinomas than control pellets (of wax alone) in the case of Ponceau 3R and l-phenylazo-2-anthrol. Ponceau 2R (MX) was inactive. Attention is drawn to the need to explain this difference between two such structurally similar food colourings (pp. 451--452). One has, however, only to compare 2-naphthylamine with the apparently harmless 1-naphthylamine (pp. 453-4) to find a parallel instance for which no clear explanation is forthcoming after decades of intensive effort. Further experiments aimed at speeding up tests for carcinogen icity (Cited in F.C.T. 1963, 1,.157 & 313) have been carried out with newborn mice and hamsters (pp. 42-3) as well as newborn rats and guinea-pigs (pp. 398-400). An extension of this approach would be the use of newborn mice in whom the thymus was removed surgically at birth (pp. 95-6) since it now appears that the thymus provides cells whose function it is to make possible the elimination of cancer cells as they arise in the body. In this way host resistance to natural or experimentally-induced cancer should be greatly reduced; so that if positive results are forthcoming with a test substance, they are more readily and consistently produced. The vexed question of the importance to be attached to mutagenic effects of compounds (Cited in F.C.T. 1963, 1, 312) comes to mind when one reads the work on macromolecules (pp. 97-8). After demonstrating that mutations could be induced in Drosophilia with biological macromolecules such as acidic and basic polypeptides, ionic synthetic polymers were tested especially strong enzyme irthibitors. Polymethacrylic acid of molecular weight about 106 proved the most potent mutagen among the macromolecules but regrettably we are not told the other polymers tested. These tests were carried out by injecting the material into fruit flies. Macromolecules can of course be taken up directly into cells, and the process has been demonstrated (pp. 112-3) with proteins entering various types of cells in tissue culture. What still remains undecided is whether macromolecules can be taken up in this way b), the cells of the intestinal epithelium; and if so, what the limiting dimensions prove to be. The barriers to diffusion of solutes into and through organs are a subject for the fruitful application of electron microscopy (pp. 103-4) and already suggestive observations are forthcoming.
WHO APPRAISAL OF ANTIBIOTICS IN FOOD Nowadays, antibiotics are applied directly to food to arrest microbiological spoilage, administered to animals for therapeutic purposes or to promote growth and used to combat plant disease. Each of these applications serve as a possible source of antibiotics in our food. In 1962, the Joint Committee of the Agricultural and Medical Research Councils of the United Kingdom could find no evidence suggesting that the presence of antibiotics in food or feeds was detrimental to public or animal health (Cited in F.C.T. 1963, 1, 42). In view of the undeniable economic advantages coupled with the negligible hazard to man, the WHO Expert Committee ("The Public Health Aspects of the Use of Antibiotics in Food and
33
plete the cycle of spermatogenesis, exposure of the male to the compound must exceed this period in order to avoid the development of spermatozoa which have not been exposed to the test substance. Space does not permit a detailed report of papers on metabolism and chemical pharmacology in relation to toxicity studies, nor of the interesting report, presented by R. Wien, of the "Study Group on the Importance of the Strains and Species of Animals used in Toxicity Tests". Suffice it to say that a great many keert and able minds are at last being brought to bear on long-neglected problems--a comforting thought.
A SUMMER PASTIME Each Spring brings the massive issue of Federation Proceedings to test the sense of dedication of the toxicologist. At least it does have a Subject Index. Not so the Annual Report of the British Empire Cancer Campaign for 1962, which comes just when the sun is shining and the garden beckons. Nevertheless, industrious scanning of its 700 pages proves rewarding (page numbers are inserted in brackets).
Inorganic agents Elsewhere in this issue (p. 107) we refer to subcutaneous tumours produced by injections of cadmium (Cd) pigments. Cd sulphate has also produced malignant tumours at the injection site in rats, as well as atrophy and tumours of the testis (pp. 34-5). The quantitative aspects are instructive. In rats as little as 2.2 mg Cd/kg given as a single dose sufficed to induce complete testicular atrophy within a few days; with 1.1 mg Cd/kg atrophy was incomplete. Elsewhere in the Report (p. 657) there is a further description of the testicular changes, which were recorded by Parizek (J. Reprod. Fertil. 1960, 1, 294) in five species. This raises the question: to what extent is man susceptible? Analysis of human testes (p. 82) revealed a range of Cd content from 0.48-2.28 ~g]g. This represents an approximate total of 19.2-91.2 ~tg for a 70-kg man. In view of the importance of possible Cd-zinc (Zn) antagonisms it is useful to note (p. 253) the number of tissue enzymes either containing firmly bound Zn or more or less specifically dependent on available Zn for maximal activity. It would be interesting, for instance, to follow the effects of Cd on the isoenzymes of the various Zn-containing dehydrogenases in the testis. The carcinogenic action of powdered metals when injected into rat muscle is exemplified by nickel and cobalt (pp. 355-7; 531). Copper, iron, tantalum and arsenic do not induce tumours under these conditions.
Envh'onmental and other factors Soil (p. 397), lubricating oil (pp. 35-6; 33), printing ink black (p. 33) and various paraffin and microcrystalline waxes (p. 33) have been studied for carcinogenicity. Results were negative, except that the lubricating oil showed a weak tumour-promoting effect. The earlierreported findings on eggs (p. 66 of this issue) contrast with the outcome of an experiment (pp. 504-5) in which chickens were maintained, from hatching to a healthy ripe old age, on a diet made up entirely of boiled eggs salted with manganese sulphate. After 1-3.5 yr no tumours developed and further experiments on eggs and egg fractions look likely to yield equally negative results.
34
SHORT REVIEWS
Organic compounds The work on lactones (pp. 158-9) is covered elsewhere in this Journal (p. 64). Further items of outstanding interest concern the metabolism of the bladder carcinogen, 2-naphthylamine (pp. 37--40) [which will be reported separately in the next issue of the Journal] and various approaches to the testing of compounds for potential carcinogenicity. Using the technique of implantation into the bladder of mice, pellets formed by compressing crushed paraffin wax with the test compound elicited more bladder carcinomas than control pellets (of wax alone) in the case of Ponceau 3R and l-phenylazo-2-anthrol. Ponceau 2R (MX) was inactive. Attention is drawn to the need to explain this difference between two such structurally similar food colourings (pp. 451--452). One has, however, only to compare 2-naphthylamine with the apparently harmless 1-naphthylamine (pp. 453-4) to find a parallel instance for which no clear explanation is forthcoming after decades of intensive effort. Further experiments aimed at speeding up tests for carcinogen icity (Cited in F.C.T. 1963, 1,.157 & 313) have been carried out with newborn mice and hamsters (pp. 42-3) as well as newborn rats and guinea-pigs (pp. 398-400). An extension of this approach would be the use of newborn mice in whom the thymus was removed surgically at birth (pp. 95-6) since it now appears that the thymus provides cells whose function it is to make possible the elimination of cancer cells as they arise in the body. In this way host resistance to natural or experimentally-induced cancer should be greatly reduced; so that if positive results are forthcoming with a test substance, they are more readily and consistently produced. The vexed question of the importance to be attached to mutagenic effects of compounds (Cited in F.C.T. 1963, 1, 312) comes to mind when one reads the work on macromolecules (pp. 97-8). After demonstrating that mutations could be induced in Drosophilia with biological macromolecules such as acidic and basic polypeptides, ionic synthetic polymers were tested especially strong enzyme irthibitors. Polymethacrylic acid of molecular weight about 106 proved the most potent mutagen among the macromolecules but regrettably we are not told the other polymers tested. These tests were carried out by injecting the material into fruit flies. Macromolecules can of course be taken up directly into cells, and the process has been demonstrated (pp. 112-3) with proteins entering various types of cells in tissue culture. What still remains undecided is whether macromolecules can be taken up in this way b), the cells of the intestinal epithelium; and if so, what the limiting dimensions prove to be. The barriers to diffusion of solutes into and through organs are a subject for the fruitful application of electron microscopy (pp. 103-4) and already suggestive observations are forthcoming.
WHO APPRAISAL OF ANTIBIOTICS IN FOOD Nowadays, antibiotics are applied directly to food to arrest microbiological spoilage, administered to animals for therapeutic purposes or to promote growth and used to combat plant disease. Each of these applications serve as a possible source of antibiotics in our food. In 1962, the Joint Committee of the Agricultural and Medical Research Councils of the United Kingdom could find no evidence suggesting that the presence of antibiotics in food or feeds was detrimental to public or animal health (Cited in F.C.T. 1963, 1, 42). In view of the undeniable economic advantages coupled with the negligible hazard to man, the WHO Expert Committee ("The Public Health Aspects of the Use of Antibiotics in Food and