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A study was conducted to identify and characterise the toxic principle in Terminalia oblongata, commonly known as yellow-wood. Crude aqueous extracts of yellow-wood leaf were found to produce the same liver lesion in mice as has been reported in ruminants. The hepatotoxic fraction was isolated and identified as a hydrolysable vegetable tannin called punicalagin. When given orally, the dose required to produce toxicity was at least 20 times greater than when given intraperitoneally. Following a given dose of punicalagin, the onset and severity of liver necrosis was found to be related to the time interval after dosing. In addition to punicalagin, an unidentified nephrotoxic substance was found which was capable of producing avascular renal necrosis without liver necrosis.

Geeldikkop was induced in sheep by the oral administration of crude steroidal saponins from Tribulus terrestris. Two of the sheep developed typical lesions of geeldikkop, including birefringent crystalloid material in bile ducts and concentric periductal lamellar fibrosis. The clinical pathological changes in these sheep were also consistent with those of geeldikkop: aspartate transaminase and gamma-glutamyl transferase activities in the sera of both were elevated, and one had bilirubinaemia. A third sheep became photosensitive without typical lesions of geeldikkop in the liver or changes in the activities of liver enzymes before euthanasia. The findings of these trials are consistent with reports from abroad that ovine hepatogenous photosensitization, caused by Agave lechuguilla and Narthecium ossifragum, can be induced with crude saponins from the respective plants.

Horizontal flow-through coil planet centrifuge (CPC) and high-performance liquid chromatography (HPLC) techniques were used for separation of polar compounds from a crude ethanol extract of Oxytropis ochrocephala Bunge, a poisonous legume plant widely distributed in northwestern China. The performance of these two chromatographic methods was compared in terms of column efficiency, peak resolution, separation time, sample loading capacity, etc. The results indicated that two polar compounds in the crude extract were equally well separated by these two methods. HPLC gave comparable peak resolution in shorter separation time while its sample loading capacity was limited to the mg range. The CPC method required a long separation time, but yielded a higher purity of fractions with a much greater capacity.

A frequent cause of contact urticaria is skin exposure to the common stinging nettle (Urtica dioica). The urticaria is accompanied by a stinging sensation lasting longer than 12 h. Little is known of the cellular and molecular mechanism of stinging-nettle urticaria. After preliminary pharmacological analysis of pro-inflammatory activity in nettle stings, the cellular response of mononuclear cells, polymorphonuclear cells and mast cells was examined in six people 5 min and 12 h after nettle contact. Only mast cell numbers were significantly increased at 12 h. Ultrastructurally, some mast cells showed evidence of degranulation at 5 min and 12 h. At 12 h mast cells were closely associated with dermal dendritic cells and lymphocytes suggesting a functional unit. The mean histamine and serotonin contents of a nettle hair were found to be 6.1 ng and 33.25 pg, respectively. Nettle-sting extracts did not demonstrate histamine release from dispersed rat mast cells in vitro. These results suggest that part of the immediate reaction to nettle stings is due to histamine introduced by the nettle. However, the persistence of the stinging sensation might suggest the presence of substances in nettle fluid directly toxic to nerves or capable of secondary release of other mediators.

From the leaves of Melicope triphylla MERR., three new flavonoids (1-3) were isolated, together with nine known flavonoids, 4',5-dihydroxy-3,3',7- trimethoxyflavone (4), 5-hydroxy-3,3',4',7-tetramethoxyflavone (5), 3,3',4',5,7-pentamethoxyflavone (6), 7-hydroxy-3,3',4',5,8-pentamethoxyflavone (7), 3,3',4',5,7,8-hexamethoxyflavone (8), 5-hydroxy-3,7,8-trimethoxy-3',4'-methylenedioxyflavone (9), 7-hydroxy-3,5,8- trimethoxy-3',4'-methylenedioxyflavone (10), 3,5,7,8-tetramethoxy-3',4'-methylenedioxyflavone (11), and 5-hydroxy- 3,6,7,8-tetramethoxy-3',4'-methylenedioxyflavone (12). The structures of 1, 2, and 3 were established as 5-hydroxy-3,7-dimethoxy-3',4'-methylenedioxyflavone, 5-hydroxy-7-isopentenyloxy-3,8-dimethoxy-3',4'-methylenedioxyfl avone, and 4'-hydroxy-7-isopentenyloxy-3,3',5,8-tetramethoxyflavone by their respective chemical and spectral data. The 20 flavonoids isolated from this plant were examined for the piscicidal activities.

Although plants containing hydrolysable tannins can be hepatotoxic, such poisoning has not been reported in Indonesia despite the presence of these plants. In order to determine the hepatotoxic potential of Indonesian plants, goats were intoxicated experimentally with the Indonesian plant Climedia hirta (harendong), which contained 19% hydrolysable tannin. The prophylactic effect of Ca(OH)2 supplementation on the disease was also examined. Two groups of goats were fed for 28 days with grain-based pellets containing 50% harendong leaf or 50% harendong leaf + 8% Ca(OH)2. Two control groups were fed similar pellets containing 50% of the non-toxic elephant grass (Pennisetum purpureum) with and without 8% Ca(OH)2. Serum enzymes indicative of liver damage were monitored during the experiment and histopathological examination of selected tissues was done at the conclusion of the experiment. In goats given unsupplemented harendong pellets there was a significant increase in aspartate aminotransferase and glutamate dehydrogenase from 50.2 and 20.6 U l-1 to 219.6 and 63.3 U l-1, respectively. These changes were associated with moderate to severe nuclear plemorphism, vacuolation and megalocytosis of hepatocytes and deposits of brown pigment in the Kupffer cells. There was also nephrosis of the renal convoluted tubules and collecting ducts, abomasitis and enteritis. Biochemical and histological changes were reduced significantly in the harendong + Ca(OH)2 group and virtually absent from control groups. It is concluded that hydrolysable tannins in harendong leaf are hepato- and nephrotoxic and associated with gastroenteritis, but that poisoning may be ameliorated by Ca(OH)2 supplementation.

The mouse erythrocyte micronucleus assay has been traditionally carried out using one or two exposures to the test agent, followed by sampling at two or three postexposure times to obtain a sample near the time of the transient peak of micronucleated polychromatic erythrocytes (PCEs). We have demonstrated that frequencies of micronucleated RNA-positive (PCEs) and RNA-negative erythrocytes in blood and bone marrow come to steady state during "continuous" exposure via diet or drinking water, or during repeated daily exposures to test agents by ip injection, gavage, or inhalation. Under these exposure conditions, frequencies of micronucleated cells in peripheral blood approached steady state within 2-3 days in RNA-positive erythrocytes and in 5-6 weeks in RNA-negative erythrocytes. With exposure durations of 6 days (monocrotaline or Crotalaria seeds in diet), 10 days (triethylenemelamine, mitomycin C, 7,12-dimethylbenzanthracene, or colchicine, ip daily), 90 days (triethylenemelamine or urethan in drinking water or 1,3-butadiene via inhalation), or 2 years (benezene by daily gavage), frequencies of micronucleated cells attained and remained at steady state for prolonged periods. At steady state, frequencies of micronucleated RNA-positive cells in bone marrow samples were similar to those in RNA-positive and RNA-negative cells in peripheral blood (e.g., triethylenemelamine in drinking water at 4 micrograms/ml resulted in frequencies of micronucleated RNA-negative erythrocytes in peripheral blood of 27/1000 after 45 days of exposure and 24/1000 after 90 days, with a frequency of 28/1000 in bone marrow RNA-positive erythrocytes after 90 days). The data suggest that the efficiency of the assay would be markedly improved by using a repeated dose schedule with a single sample taken at steady state, rather than scoring multiple samples at various times after a single dose. This approach allows the frequency of micronucleated cells to be measured in a sample of bone marrow or blood obtained at almost any stage of routine toxicity testing.

Two H2O-soluble toxic kaurene glycosides 3 and 4 responsible in part for the poisonous properties of the burr of Xanthium pungens have been isolated and identified. The structures of the compounds were elucidated using high resolution 2D nmr and mass spectral techniques.

A recent report indicated that an arrow poison used by the native Indians of Rondonia, Brazil, to kill small animals was associated with profuse bleeding. The arrow poison was prepared from the bark of a tree, known locally as Tike-Uba. We have obtained bark and sap specimens from this tree and have characterized a potent anticoagulant activity in both the crude bark and sap samples as well as in more highly purified preparations. An aqueous extract of the bark significantly prolongs both prothrombin times and activated partial thromboplastin times in plasma based assays. Further fractionation of the bark extract and sap by molecular weight indicated that all of the anticoagulant activity could be isolated in a molecular weight fraction of equal to or greater than 30,000 daltons. The anticoagulant activity was also further purified by C-18 reverse phase chromatography. When highly purified preparations of the anticoagulant activity from the Tike-Uba tree were examined in specific blood coagulation enzyme assays utilizing chromogenic substrates, the highest inhibitory potency was found versus thrombin, followed by factor Xa. These studies establish the presence of a compound(s) in a Brazilian arrow poison, which potently disrupts mammalian blood clotting, and which may account for some of the observed toxicities associated with the arrows.

Comparison by GC analysis of purified alkaloid extracts of Solanum species revealed no measurable free solasodine, other spirosolanes, or any non-spirosolane steroidal alkaloid aglycones in unhydrolyzed total alkaloid fractions of fruit of Solanum elaeagnifolium Cav. (silverleaf nightshade), Solanum sarrachoides (S. villosum Lam.--hairy nightshade), Solanum dulcamara L. (European bittersweet nightshade) or Solanum melongena L. (eggplant). All alkaloidal material was apparently present as glycoside. Conversely, sprouts of Solanum tuberosum L. (potato) contained 67% of its alkaloids as glycosides, which was freed only upon hydrolysis with the remaining 33% present as free solanidine. GC/MS analysis of hydrolysates of purified extracts of the test Solanum species revealed that solasodine was a principal or sole aglycone of the alkaloid glycosides in each of the test species except Solanum tuberosum. In the latter, solanidine was the sole aglycone. Among the test species, exclusive of S. tuberosum, only S. dulcamara contained aglycones other than solasodine. In addition to solasodine, S. dulcamara contained appreciable amounts of an unknown spirosolane, an aglycone provisionally identified as soladulcidine. The induction of congenital craniofacial malformations in hamsters by high oral doses of the four Solanum species that contained mainly solasodine glycosides--S. elaeagnifolium, S. dulcamara, S. sarrachoides and S. melongena was compared to inductions of malformations by Solanum tuberosum, that contained mainly solanidane glycosides. Compared to controls, Solanum elaeagnifolium and Solanum dulcamara fruit both induced a high percentage incidence of deformed litters (20.4 and 16.3, respectively) that was statistically significant (P less than 0.001 level) while percentage incidence of deformed litters induced by Solanum sarrachoides and Solanum melongena fruit (9.5 and 7.6 respectively) were both higher than controls (3.4%), in neither case was the incidence statistically significant (P less than .05). Deformed litter incidence induced by sprouts of Solanum tuberosum was 24.0%, (P less than 0.001).

In order to clarify the mechanisms of urtication after contact with stinging plants, nettle (Urtica urens) hair and whole-plant extracts were examined for the presence of leukotriene (LT) B4 and LTC4 by reverse phase high-pressure liquid chromatography (RP-HPLC) and radioimmunoassay (RIA) and for in vitro neutrophil chemotactic activity and histamine contents. Both hair and plant extracts contained high levels of LTB4 and LTC4 by RIA as well as histamine. The presence of LTB4 was supported by RP-HPLC elution profiles and by in vitro chemotaxis. Nettle hairs therefore resemble insect venoms and cutaneous mast cells with regard to their spectrum of mediators.

A new toxic neoanisatin-derivative (1) was isolated from the pericarps of Illicium majus. The structure of this compound was elucidated by spectroscopic data, including the 2D COSY NMR technique. The toxicity of compound 1 is also described.

Dried alcoholic extract of fresh Lantana camara leaves (LE), on oral administration to albino rats of both sexes, induced photodermatitis during exposure to clear sunlight for 1 hr. Its severity was related to the dose of LE and was maximal in rats exposed to sunlight from 4 to 14 hr after feeding LE and gradually declined over 40 hr. Wavelengths of light about 540 to 570 mu only were effective. In control study, the alcoholic extract of edible spinach leaves was only 1/3 in potency and its effect lasted for less than 20 hr. LE did not raise serum bilirubin, SGOT, SGPT or cause liver injury as assessed by light microscopy. However, like CCL4 but unlike spinach extract, LE impaired excretion of BSP by liver, proportionate to the dose and also maximal at 5.5 hr declining thereafter over 40 hr.

The most important grass species on the ovine white-liver disease (OWLD) pastures (S) were Poa spp., Agropyron repens and Lolium perenne, while the control pastures (H), where lambs grew well, consisted of Poa spp., Festuca rubra and Agrostis tenuis. The soil was more acidic on the H pastures as compared with the S pastures. OWLD grass (S grass) contained marginal to deficient amounts of cobalt during the first 2 months of grazing. During 2 years out of 3, the average Co content was slightly lower in the S grass as compared with the content in the H grass. The lowest average grass Co was, however, found during one year in the H grass, in spite of the fact that the H lambs also this year grew well, and were 13 kg heavier than the S lambs after 3 1/2 months on pasture. Results thus indicate that the H lambs some years were subclinically Co deficient, without developing clinical symptoms or OWLD, and that factors other than marginal/deficient grass Co are of importance as to whether OWLD will develop or not. S grass differed from H grass by having significantly lower copper, molybdenum, manganese and zinc content, lower protein N/amid N ratios and higher aluminium and iron contents. According to the results, marginal to deficient grass Co is essential for development of OWLD, but cofactors play a part.

Abrin A was purified from the seeds of the Abrus precatorius plant and its physical and biological properties were studied. The biological properties of abrin A were found to be similar to the better studied Abrus protein, abrin C, in that it is toxic to cell-free protein synthesis and binds D-galactose. Abrin A contains carbohydrate moieties including both neutral and amine sugars but no metals, similar to the other two Abrus proteins (abrin C and the Abrus agglutinin). Amino acid compositions of the subunits of abrin A indicated that it consists of two different subunits of comparable size. Furthermore, one of the subunits showed microheterogeneity suggesting that abrin A is a mixture of isolectins. A comparative study of abrin A and abrin C based on compositions and tryptic maps reveals them to be closely related. The evidence suggests that the two abrins may have the same mechanisms of toxic action. Far-ultraviolet circular dichroic studies of abrin A show it to contain 47% beta-pleated sheet and 10% alpha-helix, again similar to the other two Abrus proteins.

Euphorbia serrata latex has initially ingenol-3-palmitate, which by action of silica gel is converted to ingenol-20-palmitate. The former is responsible for the irritant and cocarcinogenic activity of the latex on mouse ear and on mice back skin.

An attempt to clarify the taxonomy, the biogeography and the ethnobotany of the fishing poisons of Guiana and adjacent countries is presented. Collections have been made for every drug and field-notes concerning all ethnic groups of Guiana. Data are compared with published sources, particularly those of the past centuries. Ichthyotoxic plants have been classified into three groups: rotenone-yielding plants (Lonchocarpus, Derris, Tephrosia), saponin-yielding plants (Sapindaceae), and the "kunami" group of plants (Compositae, Euphorbiaceae). For each drug the vernacular names, the synonyms still used, the most notable morphological characteristics are specified, as well as ethnological observations and active constituents when known. Drugs and fishing-related techniques were selected long ago by Amerindians then often diffused through Amazonian countries by mixed-blood populations.

The toxic principle of Cnestis glabra, identified as methionine sulfoximine has been found as a permanent constituent of the soluble amino acid pool of this plant. In the roots the toxin concentration varies markedly according to the developmental stage of the plant. The poisonous principles of Cnestis polyphylla and Rourea orientalis, two other Connaraceae species, were purified to homogeneity. Similarity of their physiochemical and biological properties, their behaviour in thin-layer and gas chromatographies and their infrared spectra to those of the toxin of Cnestis glabra established their identity to methionine sulfoximine. This methionine derivative, never reported as a natural product, seems to be characteristic of toxic Connaraceae species.

Edible lupine seeds are being marketed in Edmonton. The cooking instructions are very elaborate and are intended to remove toxic alkaloids. No warning is given on the packing to indicate that the seeds are potentially poisonous if the cooking instructions are not followed. A complaint to Alberta's Poison Control Centre indicated that problems may arise if the cooking instructions are dismissed as rigmarole. The purpose of this report is to alert poison control centres and other toxicologists of the potential toxicity of "edible lupines" when cooking instructions are not followed.

Lathyrism, one of the oldest neurotoxic diseases known to Man, results from excessive consumption of the chickling pea, Lathyrus sativus, and certain related species. Once prevalent throughout Europe, N. Africa, Middle East and parts of the Far East, the disease is presently restricted to India, Bangladesh and Ethiopia. Lathyrism is a form of irreversible, non-progressive spastic paraparesis associated with poorly understood degenerative changes in spinal cord. Domestic animals, notably the horse, also develop hindlimb paralysis after prolonged feeding on lathyrus fodder. Experimental animal models of lathyrism have been reported but none has been satisfactorily investigated, and concurrence between these experimental diseases and the human condition is unproven. The culpable agent in lathyrus species that precipitates paralysis also is unknown. Current attention is focused on the glutamate analog, beta-(N)-oxalyl-amino-L-alanine acid (BOAA). While this compound is present in those lathyrus species that induce spastic paraparesis and, in large doses, reportedly causes neuropathological changes similar to glutamate neurotoxicity, there is little to compare these neuropathological changes with those found in human lathyrism. Chronic primate feeding studies utilizing BOAA need to be carried out to determine whether this agent is responsible for human lathyrism. Some species of lathyrus, notably Lathyrus odoratus, are unable to induce human lathyrism but contain a compound, beta-aminopropionitrile (BAPN), that induces pathological changes in bone ("osteolathyrism") and blood vessels ("angiolathyrism") of experimental animals without damaging the nervous system. However, related compounds, dimethylaminopropionitrile (DMAPN) and beta, beta'-iminodipropionitrile (IDPN), are chronic neurotoxins in humans and animals, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Furocoumarins from chloroform extraction of Heracleum laciniatum were separated by high pressure liquid chromatography (HPLC) with microparticulate silica gel column investigating different concentrations of acetonitrile and water, acetonitrile and methanol and acetonitrile, methanol and water for mobile phase. With a mixture of 42:43:15 of the latter for mobile phase optimal separation was obtained of the 6 furocoumarins from the plant. Removal of lipid fractions of plant extractions with hexane is recommended to avoid damage to the HPLC column.

The latex of Euphorbia poissonii was found to contain irritant aromatic diterpene esters based upon resiniferonol, 12-deoxy-16-hydroxy-phorbol and 12-deoxyphorbol. Four resiniferonol esters, 9,13,14-ortho-phenylacetyl-resiniferonol-20-0-[p-hydroxy-phenylacetate]; 9,13,14-orthophenylacetyl-resiniferonol-20-0-[m-methoxy-m'-hydroxy-phenylacetate]; 9,13,14-orthophenylacetyl-resiniferonol-20-0-acetate and resiniferonol-14-0-phenylacetate-20-0-[m-methoxy-m'-hydroxy-phenylacetate], were identified. Two further esters were identified as 12-deoxy-16-0-[2-methylbutyroyl]-phorbol-13-0-phenylacetate-20-0-acetate and 12-deoxy-16-0-[2-methylbutyroyl]-phorbol-13-0-phenylacetate. These compounds represent the first aromatic esters of this parent diterpene to be obtained from natural sources. The third group of compounds were identified as 12-deoxyphorbol-13-0-[p-hydroxy-phenylacetate]-20-0-acetate; 12-deoxyphorbol-13-0-[p-acetoxy-phenylacetate]-20-0-acetate; 12-deoxyphorbol-13-0-phenylacetate-20-0-acetate and 12-deoxyphorbol-13-0-phenylacetate. The irritant potency of the ten pure compounds was obtained using a mouse ear method for assessment of the irritant dose 50%.

Cardiac glycoside poisoning from the ingestion of plants, particularly of oleanders, occurs with reasonable frequency in tropical and subtropical areas. We have assessed a variety of plant specimens for their cardiac glycoside content by means of radioimmunoassays with antibodies that differ in their specificity for cardiac glycosides. Significant amounts of immunoreactive cardiac glycoside were found to be present in the ornamental shrubs: yellow oleander (Thevetia peruviana); oleander (Nerium oleander); wintersweet (Carissa spectabilis); bushman's poison (Carissa acokanthera); sea-mango (Cerbera manghas); and frangipani (Plumeria rubra); and in the milkweeds: redheaded cotton-bush (Asclepias curassavica); balloon cotton (Asclepias fruiticosa); king's crown (Calotropis procera); and rubber vine (Cryptostegia grandifolia). The venom gland of the cane toad (Bufo marinus) also contained large quantities of cardiac glycosides. The competitive immunoassay method permits the rapid screening of specimens that are suspected to contain cardiac glycosides. Awareness of the existence of these plant and animal toxins and their dangers allows them to be avoided and poisoning prevented. The method is also useful for the confirmation of the presence of cardiac glycosides in serum in cases of poisoning.

The mangrove plant Heritiera littoralis has been utilized by natives of the Philippines as a fish poison. The petroleum ether extract of this plant has shown toxicity to fish (Tilapia nilotica). A new piscicide, which was assigned the name heritonin [1], has been identified as one of the compounds with ichthyotoxicity. The structure was elucidated by spectroscopic methods.

Hemlock water dropwort (Oenanthe crocata) is probably the most poisonous plant in the British Isles. The roots are the most toxic part of the plant and have been eaten in mistake for the roots of several other plant species with often fatal results. A recent nonfatal case of poisoning is reported and previous cases reviewed. Present evidence suggests that barbiturates, particularly short-acting agents are life saving and are the drugs of choice in the treatment of the convulsions.

X-band electron-paramagnetic-resonance spectroscopy at 4.2--77K combined with measurements of oxidation-reduction potential was used to identify iron--sulphur centres in Arum maculatum (cuckoo-pint) mitochondria. In the oxidized state a signal with a derivative maximum at g = 2.02 was assigned to succinate dehydrogenase centre S-3. Unreduced particles showed additional signals at g = 2.04 and 1.98 (at 9.2 GHz), which may be due to a spin-spin interaction. In the reduced state a prominent signal at g = 1.93 and 2.02 was resolved into at least three components that could be assigned to centres S-1 and S-2 of succinate dehydrogenase (midpoint potentials -7 and -240 mV respectively at pH 7.2) and a small amount of centre N-1b (e'o= -240 mV) of NADH-ubiquinone reductase. In addition, changes in line shape around -10 mV indicated the presence of a fourth component in this signal. The latter was more readily reduced by NADH than by succinate, suggesting that it might be associated with the external NADH dehydrogenase. The iron-sulphur centres of NADH-ubiquinone reductase were present in an unusually low concentration, indicating that the alternative, non-phosphorylating, NADH dehydrogenase containing a low number of iron-sulphur centres may be responsible for most of the high rate of oxidation of NADH.

Iceland lichen (Cetraria islandica) is sold in health food stores to prevent various disorders. In olden times it and sometimes also reindeer lichen (Cladonia sp.) have been used as emergency food. Lichen contains bitter and potentially toxic lichen acids and it also concentrates heavy metals. Therefore lichen toxicity was studied with traditional pretreatment methods (boiling, ash-soaking or both). Untreated and only shortly boiled lichens were lethally toxic to mice in 50 and 25% w/w mixtures in food, but when ash-soaking was added mice tolerated Cetraria (but not Cladonia) reasonably well for 3 weeks. In a 3 month test in rats 25% mixture of Cladonia was tolerated well and blood tests were normal at the end. However, urinary protein was increased, the autopsies revealed kidney changes corresponding to a mild heavy metal poisoning, as the lead concentrations in kidney and lichen were high.

The absorbance spectrum of tullidinol, a tullidora (Karwinskia humboldtiana) toxin, showed peaks at 260 and 410 nm when dissolved in ethanol; the second peak was linearly related to toxin concentration. Silica gel thin layer chromatograms of tullidinol solutions showed a single, yellow spot with an Rf of 0.76. A single dose of tullidora fruit homogenate was orally given to male Wistar rats; the absorbance spectrum of serum from tullidora-treated rats showed peaks at 300 nm and at 410 nm; the second peak was absent in serum from control rats. No spots were detected in chromatograms of normal serum, but a yellow spot with the same Rf as that of tullidinol was found in the serum of tullidora-treated rats. We conclude that tullidinol was detected in the serum of treated animals and that the methods we used for its detection may also help to diagnose accidental tullidora poisoning in cattle and human beings.

The toxicity of Thesium lineatum is confirmed in sheep. A toxic crystalline bufadienolide, with the suggested trivial name thesiuside, has been isolated from it. This is the first cardiac glycoside to be isolated from a member of the Santalaceae. The toxin appears to have no cumulative effect and the symptoms of intoxication and pathology in sheep are similar to that expected from acute cardiac glycoside intoxication.

1. Modeccin, the toxin of Adenia digitata (Modecca digitata), was purified from the roots of this plant by affinity chromatography on Sepharose 4B. 2. This toxin is a protein with mol.wt. 57000, which on treatment with 2-mercaptoethanol can be dissociated into two subunits of mol.wts. 25000 and 32000. 3. Modeccin inhibits protein synthesis in vitro in a lysate of rabbit reticulocytes and in Ehrlich ascites cells; the effect on cells is decreased in the presence of lactose. 4. Dissociation of modeccin into subunits decreases the toxicity to animals and the inhibition of protein synthesis in cells, but enhances the inhibition of protein synthesis in the lysate system.

A method is described for testing of diterpene esters for irritancy. The technique involves the application of acetone solutions of the toxins to the inside ears of female LACA mice. The number of mice responding per group and the log10 dose data were evaluated using probit analysis with the assistance of a computer program. This evaluation has the advantage that approximations inherent with an arithmetical evaluation were eliminated, and limits may be placed upon the standard deviation of the irritant dose 50% (ID50). In addition, the use of a chi2 test automatically eliminated results which were not attributed to random biological variation. Observations of the time to onset and the persistence of the inflammation have led to the suggestion that daphnane orthoester diterpenes may elicit their effect by means of a direct action at a receptor site in skin, whereas the tigliane O-acyl esters may in part act by causing more general tissue damage.

Perilla ketone, from the essential oil of Perilla frutescens, is a potent pulmonary edemagenic agent for laboratory animals and livestock. This finding would account for reported effects of the plant on grazing cattle. The use of perilla in oriental foods and medicinal preparations suggests possible hazards to human health as well.