(S)-5-エテニル-2-オキサゾリジンチオン

Goitrin is a potent goitrogen that has been shown to induce glutathione S-transferase (GST) activity and to increase aflatoxin detoxification.

goitrin --a naturally occurring compound in cruciferous vegetables and rape--could be easily nitrosated by treatment with nitrite under stomach conditions, yielding with loss of sulfur the N-nitroso- oxazolidone 4. This product has a mutagenicity pattern and potency similar to that of N-nitroso-N-methyl-N'- nitroguanidine (MNNG) in the Ames Salmonella/mammalian microsome test.

When rape cake was fed /to cows/ at 0.39, 1.9 and 3.9% resp. of the total feed this resulted in medium goitrin values of 37, 163 and 707 micrograms/l milk. These values correspond to a transfer of about 0.1% of the original progoitrin content in the feed. 12 h after the last rape feeding the amount of goitrin in the milk was below the detection limit of 7 ppb.

/LABORATORY ANIMALS: Acute Exposure/ Antithyroid activity of orally administered goitrin was assessed by parallel-line assay in chicks using four indices. The relative potency of goitrin in chicks was estimated to be approximately 0.31 times the potency of PTU in causing enlargement of thyroid gland, 0.06 times in effect on depression in plasma thyroid hormone, and 0.08 times in inhibitory effects on biosynthesis of thyroid hormone in the gland. It might be concluded that thyroid hormone synthesis is not so much suppressed to the degree expected from the enlargement of thyroid gland when goitrin is administered orally to the chick.

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Effects of dietary R-goitrin (200 ppm) ... on GST activity, binding of aflatoxin B1 (AFB1) to DNA, in vivo, and biliary excretion of thiol conjugates of AFB1 in rats were studied. Increases of GST activities (1.9-fold) were accompanied by reductions in AFB1-DNA binding (43%) and increases (1.7-fold) in biliary excretion of AFB1-thiol conjugates in R-goitrin ...groups... . Microsomal aflatoxin 8,9-epoxidase activities were not increased in either treatment group.

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ In male and female rats, R-goitrin treatment increased the relative liver weights; in some of the enlarged livers a high incidence of mitotic figures was observed. R-goitrin treatment increased the relative thyroid weight, more in male rats than in females. The thyroids of R-goitrin treated rats were either hyperplastic or had most follicles filled with pale-staining colloid and rarely follicles with normal, well-stained colloid. At certain doses, R-goitrin increased serum triglycerides, cholesterol, total protein, albumin and calcium, but it decreased serum thyroxine and urea. However, most of these changes in serum chemistry were small. R-goitrin caused a temporary increase in urinary ascorbic acid output in both sexes, but the liver ascorbic acid level was increased only in female rats. The duration of pentobarbital-induced sleep was significantly prolonged by R-goitrin pretreatment only in male rats.

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Diets containing 500 g high-glucosinolate rapeseed meal/kg or an equivalent amount of soybean meal as the only protein supplement were fed to layer-type chickens and two broiler strains from 1 to 56 days of age. Additional groups of the former were maintained on the diets until they were 16 and 28 days old. The rapeseed meal produced thyroid hypertrophy in all strains but reduced the growth rate of only one of the broiler strains. The livers of chickens fed on rapeseed meal were enlarged and DNA analysis indicated hyperplasia, but no macroscopic lesions were found. The activities of aspartate transaminase, lactate dehydrogenase and alkaline phosphatase in the plasma were increased by rapeseed meal, suggesting liver damage. In all strains, feeding rapeseed meal increased plasma total protein, albumin and cholesterol and decreased urate. Hyperglycemia accompanied by a decrease in plasma triglycerides occurred in the layer strain. Through its extra-thyroidal toxicity (-)5-vinyl-oxazolidine-2-thione (goitrin) was probably responsible for most of these changes./rapeseed/

For more Non-Human Toxicity Excerpts (Complete) data for GOITRIN (10 total), please visit the HSDB record page.

Basic treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poison A and B/

Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/

A wide variety of chemicals, drugs, and other xenobiotics affect the second step in thyroid hormone biosynthesis. The stepwise binding of iodide to the tyrosyl residues in thyroglobulin requires oxidation of inorganic iodide (I2) to molecular (reactive) iodine (I2) by the thyroid peroxidase present in the luminal aspect (microvillar membranes) of follicular cells and adjacent colloid. Classes of chemicals that inhibit the organification of thyroglobulin include ... the thionamides (such as ... goitrin)... .

A total of six cows, divided into 3 groups, were fed various amounts of rape cake containing 6 g of goitrin/kg over a period of 7 days. The cows were milked twice a day ... . When rape cake was fed at 0.39, 1.9 and 3.9% resp. of the total feed this resulted in medium goitrin values of 37, 163 and 707 ug/l milk. These values correspond to a transfer of about 0.1% of the original progoitrin content in the feed. 12 h after the last rape feeding the amount of goitrin in the milk was below the detection limit of 7 ppb.