1'-하이드록시사프롤

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ 1'-hydroxysafrole ... produced a greater incidence of liver tumors in male infant mice than did equimolar concn of safrole; 4 sc injections were given on days 1, 7, 14 & 21 of life. In male rats given 5500 mg 1'-hydroxysafrole/kg of diet for 8.5-10 mo, incidence of liver tumors in rats killed at 12 or 16 mo was higher than that in rats receiving safrole; in addn, forestomach papillomas were produced by 1'-hydroxysafrole. when groups of 18 adult rats ... given twice weekly sc injections of 18.6 umol 1'-hydroxysafrole or 1'-acetoxysafrole for 10 wk, followed by observation for 17-18 mo, local tumors occurred in both groups. A high incidence (20/65) of interscapular sarcomas (mainly angiosarcomas)...observed in mice fed 1'-hydroxysafrole.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ The hepatocarcinogen 1'-hydroxysafrole (HOS) exhibited weak initiating activity and strong promoting activity for the induction of enzyme-altered foci and tumors in rat liver. Thus, administration of a single dose of HOS to rats 18 hr after a 70% hepatectomy, followed by administration of phenobarbital (PB) in the diet for 6 months, induced a low, but statistically significant, number of foci of enzyme-altered cells. This treatment did not result in gross liver tumors, even when the PB treatment was continued for 16 months. Large numbers of enzyme-altered foci developed when HOS was administered in the diet at levels of 0.05-0.25% to rats previously administered a single dose of N,N-diethylnitrosamine (DEN) 24 hr after a 70% hepatectomy. Similarly, rats given a single dose of DEN 24 hr after a partial hepatectomy and then fed 0.10 or 0.25% of HOS in the diet for 10 months developed a high incidence of hepatocellular carcinomas. In the absence of pretreatment with DEN, dietary administration for at least 4 months of 0.10 or 0.25% of HOS induced significant numbers of enzyme-altered foci; these data and liver tumor induction by continuous feeding of HOS, in the absence of pretreatment with DEN, provide additional evidence for an initiating, as well as a promoting, activity of HOS in rat liver. Concurrent administration of the hepatic sulfotransferase inhibitor pentachlorophenol with HOS in each of the above assays almost completely inhibited the initiating and promoting activities of HOS for the formation of enzyme-altered foci and tumors; these data strongly suggest that both the initiating and promoting activities are mediated by the sulfuric acid ester, 1'-sulfooxysafrole. HOS also exhibited initiating activity in adult mouse liver. Thus, dietary administration of 0.25% of HOS for only 1 month, followed by administration of the hepatic tumor promoter 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene resulted in a high incidence and multiplicity of hepatomas by 10 months. In the absence of the promoter, administration of HOS for only 1 month induced no hepatomas; 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene alone induced only a low incidence. In mice not given the promoter, continuous administration of HOS for 3-6 months was required for hepatoma development by 16 months.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Safrole and 1'-hydroxysafrole were fed in the diet to adult mice at final levels of 0.50 and 0.55%, respectively, for 12 months. The survivors were sacrificed at 17 months. A control group was included and the number of mice per sex per group ranged from 45 to 55. It was necessary to increase the dietary level of 1'-hydroxysafrole gradually because the 0.55% level was acutely toxic in uninitiated females. The acute toxicity was associated with marked liver toxicity. Both safrole and 1'-hydroxysafrole produced depression of weight gain and increased mortality by the end of 12 months of treatment. No liver tumors were observed in either the male or female controls. Eleven male and 25 female safrole- treated mice had liver tumors. No male mice and 30 female 1'-hydroxysafrole-treated mice had liver tumors. There were also five sc angiosarcomas in the female 1'-hydroxysafrole-treated mice.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ ... A total dose of 4.43 umol of 1'-hydroxysasfrole was administered sc to preweanling male mice. The dose was divided and administered on days 1, 8, 15 and 22 of age. The test groups contained 60 mice and the control group 66. The mice were sacrificed at 15 months of age. Six control mice had liver carcinomas; none were multiple. Thirty test mice had liver tumors; these tumors were multiple in 20 of the mice.

For more Non-Human Toxicity Excerpts (Complete) data for 1'-HYDROXYSAFROLE (11 total), please visit the HSDB record page.

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if necessary. 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 0.9% saline (NS) during transport ... . Administer activated charcoal ... . Do not use emetics. Cover skin burns with dry, sterile dressings after decontamination ... . Maintain body temperature. /Phenols and related compounds/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Monitor cardiac rhythm and treat arrhythmias if necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Consider vasopressors if patient is hypotensive with a normal fluid volume. Watch for signs of fluid overload ... . Administer 1% solution methylene blue if patient is symptomatic with severe hypoxia, cyanosis, and cardiac compromise not responding to oxygen. ... Treat seizures with diazepam or lorazepam. ... Use proparacaine hydrochloride to assist eye irrigation ... . /Phenols and related compounds/

When 1'-hydroxysafrole was given orally or by ip injection to male rats, about 40% was excreted unchanged; this was not affected by phenobarbital or 3-methylcholanthrene admin. No 1'-hydroxysafrole was excreted in the bile.

The urinary metabolites of 1'-hydroxysafrole included 3'-hydroxyisosafrole, 3,4-methylenedioxyphenyl vinyl ketone, the dimethylamino & piperidyl mannich bases, & 3,4-methylenedioxyhippuric acid ...

In men & rats, small oral doses of safrole were absorbed rapidly & then excreted almost entirely within 24 hr in the urine. 1'-hydroxysafrole, a proximate carcinogen of safrole, & 3'-hydroxyisosafrole were detected as conjugates in the urine of the rat; however, it was not possible to demonstrate their presence in man.

In the neutral extraction of urine from animals injected with 1'-hydroxysafrole, unmetabolized 1'-hydroxysafrole, 3'-hydroxyisosafrole, 3,4-methylenedioxyphenyl vinyl ketone & 2 unidentified metabolites (mol wt 180 & 226) were present. In the basic urine extraction, the dimethylamino & piperidyl mannich base metabolites were detected; the only acidic metabolite found was 3,4-methylenedioxyhippuric acid.

For more Metabolism/Metabolites (Complete) data for 1'-HYDROXYSAFROLE (8 total), please visit the HSDB record page.