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Acute bracken poisoning in homogastric and ruminant animals

Published online by Cambridge University Press:  05 December 2011

W. Charles Evans
Affiliation:
Department of Biochemistry and Soil Science, University College of North Wales, Bangor, Gwynedd LL57 2UW, Wales
M. C. Patel
Affiliation:
Department of Biochemistry and Soil Science, University College of North Wales, Bangor, Gwynedd LL57 2UW, Wales
Y. Koohy
Affiliation:
Department of Biochemistry and Soil Science, University College of North Wales, Bangor, Gwynedd LL57 2UW, Wales
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Synopsis

The toxicity of bracken fern (Pteridium aquilinum (L) Kuhn) is complicated because this plant elaborates more than one type of agent potentially harmful to livestock.

When simple-stomached animals are fed a diet containing some green fronds or rhizomes for a few weeks, they develop anorexia and inco-ordination symptoms; this polyneuritic syndrome shows all the characteristics of thiamine deficiency. Thiamine therapy is effective in curing the animal provided it is administered at the onset of clinical symptoms.

Bracken staggers in the horse and rhizome poisoning of pigs are diseases of this nature,i.e. an avitaminosis B1 has been induced. The causative agent in the fern is a steam-labile enzyme, thiaminase I, which destroys thiamine in such a way that it is no longer active in animal nutrition.

Acute cattle bracken poisoning occurs after frequent eating of the fern over a period of weeks.Haemorrhages and fever are the characteristic clinical symptoms, and the animal usually dies within a few days. The fundamental lesion is bone marrow aplasia resulting in a severe leucopenia and thrombocytopenia.Thiaminase I is not involved in this disease. Bracken contains an organic chemical(s) which poisons rapidly dividing cells in the bovine animal. Sheep are less sensitive to this toxic agent, although the condition has been described along with 'bright-blindness* in some parts of Britain (e.g. North York Moors).

Purification of the active principle causing cattle bracken poisoning from green fronds and rhizomes is far advanced; these methods are described, along with calf toxicity tests on each fraction. Chemical investigations are also under way to determine the nature of the components.

Whether the cattle factor, in small doses over an extended period of time (years), is also the agent causing tumours in livestock, is probable but not certain. Some bracken constituents shown to be carcinogenic in small animals, e.g. shikimic acid, quercetin or the tannin fraction, are not capable of producing acute cattle bracken poisoning; neither does safrole or 1-indanone.

Some of the sesquiterpene glycosides—the 'pterosides' and/or their aglycones, the 'pterosins', of which over 30 have been identified in bracken—are likely candidates. On the other hand, the active principle(s) may be something quite different; the search continues.

Type
Research Article
Copyright
Copyright © Royal Society of Edinburgh 1982

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References

Almond, N. 1894. Fern poisoning.J. Comp. Path. 7, 165167.Google Scholar
Ambrose, A. M., Robbins., D. J. and DeEds, F. 1952. Comparative toxicities of Quercetin and Quercitrin. J. Am. Pharm. Ass. Sci. Edn 41, 119122.CrossRefGoogle Scholar
Ames, B. N., McCann, J. and Yamasaki, E. 1975. Methods for detecting carcinogens and mutagens with Salmonella/Mammalian-Microsome Mutagenicity Test. Mutation Res. 31, 347364.CrossRefGoogle ScholarPubMed
Barnhurst, J. D. and Hennessy, D. J. 1952. The action of fish tissue on Thiamine. Identification of the Pyrimidine Moiety of Icthiamin J. Am. Chem. Soc. 74, 356358.CrossRefGoogle Scholar
Boddie, G. F. 1947. Toxicological problems in veterinary practice. Vet. Rec. 59, 470479.Google ScholarPubMed
Berti, G. and Bottari, F. 1968. Constituents of ferns. In Progress in Phytochemislry, ed. Reinhold, L. and Liwschitz, Y. Vol. 1, pp. 589685. London, New York and Sydney: Interscience.Google Scholar
Brown, J. P., Dietrich, P. S. and Brown, R. J. 1977. Frameshift mutagenicity of certain naturally occurring phenolic compounds in the Salmonella/microsome test: Activation of anthraquinone and flavonol glycosides by gut bacterial enzymes. Biochem. Soc. Trans. 5, 14891491.CrossRefGoogle ScholarPubMed
Carpenter, K. J., Phillipson, A. T. and Thompson, W. 1950. Experiments with dried Bracken (Pteris aquilinum). Br. Vet. J. 106, 292308.CrossRefGoogle Scholar
Clark, I. A. and Dimmock, Corinne K. 1971. The toxicity of Cheilanthes sieberi to cattle and sheep. Aust. Vet. J. 47, 149152.CrossRefGoogle ScholarPubMed
Cooper-Driver, G. 1976. Chemotaxonomy and phytochemical ecology of bracken. Bot. J. Linn. Soc. 73, 3546.CrossRefGoogle Scholar
Dobereiner, J., Tokarnia, C. H. and Canella, F. C. 1967. Occurrence of enzootic haematuria and epidermoid carcinoma of the upper digestive tract of cattle in Brazil. Pesq. Agropec. Brazil 2, 489504.Google Scholar
Ebata, J. and Murata, K. 1961. The purification of thiaminase I produced by Bacillus thiaminolyticus. J. Vitam. 7, 115121.CrossRefGoogle ScholarPubMed
Edwin, E. E. and Jackman, R. 1970. Thiaminase I in the development of cerebrocortical necrosis in sheep and cattle. Nature, Lond. 228, 772774.CrossRefGoogle ScholarPubMed
Edwin, E. E. and Jackman, R. 1974. A rapid radioactive method for the determination of thiaminase activity and its use in the diagnosis of cerebrocortical necrosis in sheep and cattle. J. Sci. Fd Agric. 25, 357368.CrossRefGoogle ScholarPubMed
Edwin, E. E., Jackman, R., Machin, A. F. and Quick, M. P. 1976. The importance of Δ′-pyrroline in the aetiology of cerebrocortical necrosis. Biochem. Biophys. Res. Commun. 70, 11901197.CrossRefGoogle Scholar
Evans, C. A., Carlson, W. E. and Green, R. G. 1942. The pathology of Chastek paralysis in foxes. A counterpart of Wernicke's haemorrhagic polioencephalitis in man. Am. J. Path. 18, 7990.Google Scholar
Evans, E. T. R., Evans, W. C. and Hughes, L. E. 1951. Developments in the investigation into bracken poisoning in cattle. Vet. Rec. 63, 444.Google Scholar
Evans, I. A. 1968. The radiomimetic nature of bracken toxin. Cancer Res. 28, 22522261.Google ScholarPubMed
Evans, A. 1976. Relationship between bracken and cancer. Bot. J. Linn. Soc. 73, 105112.CrossRefGoogle Scholar
Evans, A. 1979. Bracken carcinogenecity. Res. Vet. Sci. 26, 339348.CrossRefGoogle Scholar
Evans, A. and Howell, R. M. 1962. Bovine bracken poisoning. Nature, Lond. 194, 584585.CrossRefGoogle ScholarPubMed
Evans, A., Humphreys, D. J., Goulden, L., Thomas, A. J. and Evans, W. C. 1963. Effects of bracken rhizomes on the pig. J. Comp. Path. 73, 229243.CrossRefGoogle ScholarPubMed
Evans, A.. and Mason, J. 1965. Carcinogenic activity of bracken. Nature, Lond. 208, 913—914.CrossRefGoogle ScholarPubMed
Evans, A. and Osman, M. A. 1974. Carcinogenecity of bracken and shikimic acid. Nature, Lond. 250, 348349.CrossRefGoogle Scholar
Evans, W. C. 1975. Thiaminases and their effects on animals. Vitams Horm. 33, 467504.CrossRefGoogle ScholarPubMed
Evans, W. C., Evans, E. T. C. and Hughes, L. E. 1954. Studies on bracken poisoning in cattle. Pts I, II and III. Br. Vet. J. 110, 295306; 365–380; 426–444.CrossRefGoogle Scholar
Evans, W. C. and Evans, E. T. R. 1949. The effects of the inclusion of bracken (Pteris aquilina) in the diet of rats, and the problem of bracken poisoning in farm animals. Br. Vet. J. 105, 175186.Google Scholar
Evans, W. C., Evans, E. T. R. and Roberts, H. E. 1951. Studies on bracken poisoning in the horse. Br. Vet. J. 107, 364371; 399–411.CrossRefGoogle Scholar
Evans, W. C. Evans, I. A., Axford, R. F. E., Threlfall, G., Humphreys, D. A. and Thomas, A. J. 1961. Studies of bracken poisoning in cattle. Part VII. The toxicity of bracken rhizomes. Vet. Rec. 73, 852853.Google Scholar
Evans, W. C., Evans, I. A., Chamberlain, A. G. and Thomas, A. J. 1959. Studies on bracken poisoning in cattle. Pt VI. Br. Vet. J. 115, 13.CrossRefGoogle Scholar
Evans, W. C., Evans, I. A., Humphreys, D. J., Lewin, B., Davies, W. J. and Axford, R. F. E. 1975. Induction of thiamine deficiency in sheep with lesions similar to those of cerebrocortical necrosis. J. Comp. Path. 85, 253267.CrossRefGoogle ScholarPubMed
Evans, W. C., Evans, I. A., Thomas, A. J., Watkin, J. E. and Chamberlain, A. T. 1958. Studies on bracken poisoning in cattle. Pt IV. Br. Vet. J. 114, 180267.CrossRefGoogle Scholar
Evans, W. C. and Jones, N. R. 1952. Plant Thiaminases. Biochem. J. 50, xxvii.Google Scholar
Evans, W. C., Jones, N. R. and Evans, R. A. 1950. The mechanism of the anti-aneurin activity of bracken (Pteris aquilina). Biochem. J. 46, xxxviii.Google Scholar
Evans, W. C., Widdop, B. and Harding, J. D. 1972. Experimental poisoning by bracken rhizomes in pigs. Vet. Rec. 90, 471–;475.CrossRefGoogle ScholarPubMed
Forenbacher, S. 1950. Equisetum poisoning of horses and the vitamin B complex. Vet. Arh. 20, 405471.Google Scholar
Fujita, A. 1954. Thiaminase. Adv. Enzymol. 15, 389421.Google ScholarPubMed
Fujita, A. 1972. Recollections of the background in the study of thiaminase and thermostable thiaminedecomposing factors in Japan. J. Vitam. 18, 67—72.CrossRefGoogle Scholar
Fukuoka, M., Kuroyanagi, M., Toyama, M., Yoshihira, K. and Natori, S. 1972. Pterosins J, K and L and six acylated pterosins from bracken Pteridium aquilinum var. latiusculum. Chem. Pharm. Bull., Tokyo 20, 22822285.Google Scholar
Fukuoka, M., Kuroyanagi, M., Yoshihira, K. and Natori, S. 1978. Chemical and toxicological studies on bracken fern, Pteridium aquilinum var. latiusculum. II. Structures of pterosins, sesquiterpenes having 1-indanone skeleton. Chem. Pharm. Bull., Tokyo 26, 2365—2385.CrossRefGoogle ScholarPubMed
Fukuoka, M., Kuroyanagi, M., Yoshihira, K., Natori, S., Nagao, M., Takahashi, Y. and Sugimura, T. 1978.Chemical and toxicological studies on bracken fern. Pteridium aquilinum var. latiusculum. IV. Surveys on bracken constituents by mutagen test. J. Pharm. Dyn. 1, 324331.CrossRefGoogle Scholar
Grimshaw, W. T. R. and Evans, I. A. 1980. The inter-relationship between bovine neoplasia and bracken fern (Pteridium aquilinum). Oncology Supplement. Scientific Foundations of Oncology, ed. SirSymington, T. and Carter, R. L., pp. 4960. London: Heinemann Medical Books.Google Scholar
Guilhon, J., Oloy, J. and Queinnec, G. 1955. Experimental bracken poisoning in young cattle in Brittany. Bull. Acad. Vét. Fr. 28, 457462.CrossRefGoogle Scholar
Hadwen, S. and Bruce, E. A. 1920. The experimental reproduction of bracken staggers in the horse. Br. Vet. J. 76, 98106.Google Scholar
Hasegawa, E. and Ueda, K. 1953. Studies on aneurinase. The base exchange products of thiamine. Seikagaku 25, 8190.Google Scholar
Haslam, E. 1966. Chemistry of Vegetable Tannins. London and New York: Academic Press.Google Scholar
Heath, G. B. S. and Wood, B. 1958. Bracken poisoning in cattle. J. Comp. Path. 68, 201212.CrossRefGoogle ScholarPubMed
Hirono, I., Ueno, I., Hosaka, S., Takanashi, H., Matsushima, T., Sugimura, T. and Natori, S. 1981. Carcinogenecity examination of Quercetin and Rutin in ACI rats. Cancer Lett. 13, 1521.CrossRefGoogle Scholar
Howell, R. M. and Evans, I. A. 1967. Chromatographic characteristics of fibrinogen and seromucoid in bovine bracken poisoning. J. Comp. Path. 77, 117128.CrossRefGoogle ScholarPubMed
Jarrett, W. F. H., McNeil, P. E., Grimshaw, W. T. R., Selman, I. E. and Mclntyre, W. I. M. 1978. High incidence of cattle cancer with a possible interaction between an environmental carcinogen and a papilloma virus. Nature. Lond. 274, 215217.CrossRefGoogle Scholar
Kaplanis, J. N., Thompson, M. J., Robbins, W. E. and Bryce, B. M. 1967. Insect hormones; α-ecdysone and 20-hydroxyecdysone in bracken fern. Science, N.Y. 157, 14361438.CrossRefGoogle ScholarPubMed
Kenten, R. H. 1957. The partial purification and properties of a Thiaminase from Bracken (Pteridium aquilinum (L) Kuhn.) Biochem. J. 67, 2533.CrossRefGoogle ScholarPubMed
Kimura, R. 1965. Thiamine decomposing bacteria. Review of Japanese literature on beri-beri and thiamine. Proceedings of the Vitamin B Research Committee of Japan, ed. Shimazono, N. and Katsura, E., pp. 255271. Tokyo: Igaku-Shoin.Google Scholar
Kuroyanagi, M., Fukuoka, M., Yoshihira, K. and Natori, S. 1979. Chemical and toxicological studies on bracken fern, Pteridium aquilinum var. latiusculum. III. Further characterization of pterosins and pterosides, sesquiterpenes and the glucosides having 1-indanone skeleton from the rhizomes. Chem. Pharm. Bull, Tokyo 27, 592601.CrossRefGoogle Scholar
Matsukawa, T., Misawa, H., Fujimiya, M., Kobayashi, H., Horikawa, Y. and Takato, T. 1954. Studies on thiamine deficiency due to bacterial thiaminase. I. Investigations on intestinal contents. J. Vitam. 1, 4360.CrossRefGoogle ScholarPubMed
McCleary, B. V. and Chick, B. F. 1977. The purification and properties of a Thiaminase I enzyme from Nardoo (Marsilea Drummondii) Phytochemistry 16, 207213.CrossRefGoogle Scholar
McCrea, C. T. and Head, K. W. 1978. Sheep tumours in North East Yorkshire. I. Br. Vet. J. 134, 454467;also 1981. II. Experimental Production of Tumours. Br. Vet. J. 137, 21–30.CrossRefGoogle ScholarPubMed
McKinney, L. L., Weakley, F. B., Eldridge, A. C., Campbell, R. E., Cowan, J. C., Picken, J. C. Jr. and Biester, H. E. 1957. S-(Dichlorovinyl)-L-Cysteine: An agent causing a fatal aplastic anaemia in calves. J. Am. Chem. Soc. 79, 39323933.CrossRefGoogle Scholar
Moon, F. E. and Raafat, M. A. 1951. The experimental production of ‘bracken poisoning’ in sheep. J. Comp. Path. 61, 88100.CrossRefGoogle ScholarPubMed
Morgan, K. T. and Lawson, G. H. K. 1974. Thiaminase type I—producing bacilli and ovine polioencephalomalacia. Vet. Rec. 95, 361363.CrossRefGoogle Scholar
Muller, H. 1897. Landwirtschaftliche Giftlehre (cited in Lander, 1926. Veterinary Toxicology. London: Bailliere, Tindall & Cox).Google Scholar
Murata, K. 1965. Beri-beri and Thiamine. In Proceedings of the Vitamin B Research Committee of Japan ed. Shimazono, N. and Katsura, E., p. 220. Tokyo: Igaku-Shoin.Google Scholar
Murata, K., Ebata, J., Somekawa, M. and Marukawa, S. 1968. The action of bacterial thiaminase I on thiamine. A decomposition product of thiamine, pyrimidinyl-nicotinic acid. J. Vitam. 14, 1220.CrossRefGoogle ScholarPubMed
Murata, K. and Hase, S. 1961. Pyrimidinyl-cysteine from thiamine by bacterial thiaminase I. Vitamins, Japan 23, 4956.Google Scholar
Naftalin, J. M. and Cushnie, G. H. 1951. Pathology of bracken poisoning Vet. Rec. 63, 332.CrossRefGoogle ScholarPubMed
Naftalin, J. M. and Cushnie, G. H. 1954. Experimental bracken poisoning in calves.Comp. Path. 64, 7586.CrossRefGoogle ScholarPubMed
Pamucku, A. M., Goksoy, S. K. and Price, J. M. 1967. Urinary bladder neoplasms induced by feeding bracken fern (Pteris aquilina) to cows. Cancer Res. 27, 917924.Google Scholar
Pamucku, A. M., Hatcher, J., Taguchi, H. and Bryan, G. T. 1980. Quercetin An intestinal and bladder carcinogen present in bracken fern. Proc. Am. Ass. Cancer Res. 21, 74.Google Scholar
Pamucku., A. M., Wang, C. Y., Hatcher, J. and Bryan, G. T. 1980. Oncogenecity of tannin from bracken fern. J. Natn Cancer Inst. 65, 131136.Google Scholar
Pamucku, A. M., Yalciner, S., Hatcher, J. F. and Bryan, G. T. 1980. Quercetin: a rat intestinal and bladder carcinogen present in bracken fern. Cancer Res. 40, 34663472.Google Scholar
Parker, W. H. and McCrea, C. T. 1965. Bracken (Pteris aquilina) poisoning of sheep in the North York Moors. Vet. Rec. 77, 861866.Google ScholarPubMed
Penberthy, J. 1893. Vegetable poisoning simulating anthrax in cattle. J. Comp. Path. 6, 266275.CrossRefGoogle Scholar
Peters, R. A. 1963. In Biochemical lesions and lethal synthesis, ed. Alexander, D. and Bacq, Z. N., pp. 639. Oxford: Pergamon Press.CrossRefGoogle Scholar
Peters, R. A. 1967. Ciba Fdn Study Grps 28, 18.Google Scholar
Pill, A. H. 1967. Evidence of thiamine deficiency in calves affected with cerebrocortical necrosis. Vet. Rec. 81, 178181.CrossRefGoogle ScholarPubMed
Pritchard, W. R., Rethfeld, C. E. and Sautter, J. H. 1952. Aplastic anemia of cattle associated with ingestion of Trichloroethylene extracted Soybean Oil Meal. (Stockman Disease, Duren Disease, Brabant Disease). J. Am. Vet. Med. Ass. 121, 110.Google ScholarPubMed
Roberts, H. E., Evans, E. T. R. and Evans, W. C. 1949. The production of ‘bracken staggers’ in the horse and its treatment with vitamin B1 therapy. Vet. Rec. 61, 549—550.Google Scholar
Robertson, J. A. and Evans, W. C. 1978. Mutagenecity of Bracken extracts using the Ames Salmonella strains: The activity of Quercelin and the effect of different activation systems. Report to the Agricultural Research Council and circulated to the Directors of ARC Research Institutes.Google Scholar
Robinson, W. G. 1947. In general discussion to Boddie's paper on ‘Toxicological problems in veterinary practice’. Vet. Rec. 59, 484.Google Scholar
Rosenberger, von. G., and Heeschen, W. 1960. Adlefarn (Pteris aquilina) die Ursache des sog. Stallroter der Rinder (Haematuria vesicalis bovis chronics). Dt Tierärztl. Wchschr 76, 201207.Google Scholar
Saito, M., Umeda, M., Enomoto, M., Hatahaka, Y., Natori, S., Yoshihira, K., Fukuoka, M. and Kuroyanagi, M. 1975. Cytotoxicity and carcinogenecity of pterosins and pterosides,l.indanone derivatives from bracken (Pteridium aquilinum). Experientia 31, 829831.CrossRefGoogle Scholar
Schofield, F. W. 1947. Leucopenia and agranulocytosis in some field cases of cattle bracken poisoning. Rep. Ont. Vet. Coll. p. 127.Google Scholar
Shearer, G. D. 1945. Some observations on the poisonous properties of bracken (P.A.).J. Comp. Path. 55, 301307.CrossRefGoogle Scholar
Somogyi, J. C. 1971. On antithiamine factors of fern. J. Vitam. 17, 165174.CrossRefGoogle ScholarPubMed
Somogyi, J. C. and Beruter, J. 1967. 3,4-dihydroxycinnamic acid (caffeic acid), an antithiamine factor of fern. Experientia 23, 996997.Google Scholar
Spector, W. G. 1977. An Introduction to General Pathology. Edinburgh: Churchill Livingstone.Google Scholar
Stockman, S. 1922. Bracken Poisoning of Cattle in Great Britain. J. Comp. Path. 35, 273275.CrossRefGoogle Scholar
Storrar, D. N. 1893. Cases of vegetable poisoning in cattle. J. Comp. Path. 6, 276279.CrossRefGoogle Scholar
Sugimura, T., Nagao, M., Matsushima, T., Yahagi, T., Seino, Y., Shirai, A., Sawamura, M., Natori, S., Yoshihira, K., Fukuoka, M. and Kuroyanagi, M. 1977. Mutagenecity of Flavone Derivatives. Proc. Japan Acad. 53B, 194197.CrossRefGoogle Scholar
Takatori, K., Nakano, S., Okumura, K., Hirono, I. and Shimizu, M. 1972. Pterolactam, a new compound isolated from bracken. Chem. Pharm. Bull., Tokyo 20, 1087.CrossRefGoogle Scholar
Takemoto, T., Arihara, S. and Hikono, H. 1968a. Structure of ponasteroside A, a novel glycoside of insectmoulting substance from Pteridium aquilinum var. latiusculum. Tetrahedron Lett. 39, 41994202.CrossRefGoogle Scholar
Takemoto, T., Arihara, S., Hikono, Y. and Hikono, H. 1968b. Isolation of insect moulting substances from Pteridium aquilinum var. latiusculum. Chem. Pharm. Bull., Tokyo 16, 762.CrossRefGoogle Scholar
Thomas, B. and Walker, H. F. 1949. The inactivation of thiamine by bracken (Pteris aquilina). J. Soc. Chem. Ind. Lond. 68, 69.Google Scholar
Thomas, A. J., Watkin, J. E., Evans, I. A. and Evans, W. C. 1955. Identification of proline as a natural cofactor of bracken thiaminase. Biochem. J. 61, viii.Google Scholar
Thomas, A. J., Threlfall, G., Humphreys, D. J. and Evans, W. C. 1963. Inhibition of erythropoesis in the rat by extracts of bracken fern (Pteridium aquilinum). Biochem. J. 88, 60.Google Scholar
Wang, C. Y., Chiu, C. W., Pamucku, A. M. and Bryan, G. T. 1976. Identification of Carcinogenic Tannin isolated from Bracken. J. Natn Cancer Inst. 56, 3336.CrossRefGoogle ScholarPubMed
Wang, C. Y., Pamucku, A. M. and Bryan, G. T. 1976. Bracken fern as a naturally occurring carcinogen. In “Ecological Perspectives on Carcinogens and Cancer Control”, ed. Stock, C. C., Santamaria, L., Mariani, P. and Gorini, S. Med. Biol. Environ. 4, 565–572.Google Scholar
Watson, W. A., Barnett, K. C. and Terlecki, S. 1972. Progressive retinal degeneration (bright blindness) in sheep: a review. Vet. Rec. 91, 665670.CrossRefGoogle ScholarPubMed
Wells, H. E. 1949. Bracken Poisoning. J. Minist. Agric. 56, 204208.Google Scholar
Weswig, P. H., Freed, A. M. and Haag, J. R. 1946. Antithiamine Activity of Plant Materials. J. Biol. Chem. 165, 737738.CrossRefGoogle ScholarPubMed
Widdop, B. 1967. Separation and Characterisation of Various Toxicological Components of Bracken. Ph.D. Thesis, Univ. of Wales, Bangor.Google Scholar
Wislocki, P. G., Miller, E. C., Miller, J. A., McCoy, E. C. and RosenKranz, H. S. 1977. Carcinogenic and mutagenic activities of safrole, 1-hydroxy-safrole and some known or possible metabolites. Cancer Res. 37, 18831891.Google ScholarPubMed
Wittcliff, J. L. and Airth, R. L. 1970. Thiaminase I (thiamine:base 2-methyl-4-aminopyrimidine-5-methenyl transferase, EC 2.5.1.2) and Thiaminase II (thiamine hydrolase, EC 3.5.99.2). In Methods in Enzymology, ed. McCormack, D. B. and Wright, L. D. Vol. 18 (Part A), pp. 229238. New York: Academic Press.Google Scholar
Yoshihira, K., Fukuoka, M., Kuroyanagi, M., Natori, S., Umeda, M., Morohoshi, T., Enomoto, M. and Saito, M. 1978. Chemical and toxicological studies on bracken fern, Pteridium aquilinum var. latiusculum. I. Introduction, extraction and fractionation of constituents, and toxicological studies including carcinogenecity tests. Chem. Pharm. Bull., Tokyo, 26, 23462364.CrossRefGoogle Scholar