National Toxicology Program

Selected toxicity information from HSDB, one of the National Library of Medicine's databases. ¹

Names (NTP)

• Quercetin
• 2-(3,4-DIHYDROXYPHENYL)-3,5,7-TRIHYDROXY-4H-1-BENZOPYRAN-4-ONE (9CI)

Human Toxicity Excerpts

• QUERCETIN INDUCED CHROMOSOME ABERRATIONS & SISTER CHROMATID EXCHANGE (SCE) IN HUMAN CELLS (FIBROBLASTS & LYMPHOCYTES) WITHOUT METABOLIC ACTIVATION. THE INCREMENT IN FREQUENCY OF SCE WAS DOSE-DEPENDENT & MAX FREQUENCY WAS 1.7-3.3-FOLD GREATER THAN THAT OF THE CONTROL VALUES. THE FREQUENCY OF CHROMOSOME ABERRATIONS WAS ELEVATED 1.7-7.8-FOLD COMPARED WITH CONTROLS. [YOSHIDA MA ET AL; CYTOGENETIC EFFECTS OF QUERCETIN ON CULTURED MAMMALIAN CELLS; PRC JPN ACAD, SER B 56(7) 443 (1980)]**PEER REVIEWED**
  

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Non-Human Toxicity Excerpts

• QUERCETIN...CAUSED CATARACT IN 50% OF THE RATS TO WHICH IT WAS ADMIN IN IMPURE COMMERCIAL FORM, BUT ONLY ONE EYE OF EACH RAT WAS AFFECTED, & PURIFIED QUERCETIN DID NOT PRODUCE CATARACTS. AN EXPLANATION HAS NOT YET BEEN FOUND. [Grant, W. M. Toxicology of the Eye. 2nd ed. Springfield, Illinois: Charles C. Thomas, 1974., p. 869]**PEER REVIEWED**
  
• QUERCETIN WAS MUTAGENIC TO V79 CHINESE HAMSTER CELLS IN THE ABSENCE OF RAT-LIVER (S-9) MIX...AND QUERCETIN...SHOWED UNEQUIVOCAL MUTAGENIC ACTIVITY IN SALMONELLA TYPHIMURIUM TA98 STRAIN; QUERCETIN.../WAS/ ACTIVE WITHOUT METABOLIC ACTIVATION. [The Royal Society of Chemistry. Foreign Compound Metabolism in Mammals. Volume 6: A Review of the Literature Published during 1978 and 1979. London: The Royal Society of Chemistry, 1981., p. 194]**PEER REVIEWED**
  
• PURIFIED QUERCETIN AS WELL AS DIETS CONTAINING 0.1% & 0.2% ARE MUTAGENIC TO SALMONELLA TYPHIMURIUM TA 100. RATS FED QUERCETIN DIETS FOR 64 WEEKS SHOWED NO CONSISTENT TISSUE LESIONS, CARCINOGENICITY OR REPRODUCTIVE PROBLEMS. [STOEWSAND GS ET AL; QUERCETIN: A MUTAGEN- NOT A CARCINOGEN IN FISCHER RATS; J TOXICOL ENVIRON HEALTH (IN PRESS) (1984)]**PEER REVIEWED**
  
• MICE GIVEN QUERCETIN ORALLY AT CONCENTRATIONS THAT WERE ABOUT 10+3 TIMES GREATER THAN THE ESTIMATED AVG HUMAN INTAKE OF TOTAL FLAVONOLS WERE TESTED FOR MUTAGENICITY WITH 2 COMPLEMENTARY IN VIVO MUTAGENICITY/CARCINOGENICITY SCREENING TESTS: THE MICRONUCLEUS TEST & THE HOST-MEDIATED ASSAY EMPLOYING THE AMES SALMONELLA TESTER STRAIN TA98. NO MUTAGENIC EFFECT WAS DETECTED WITH EITHER TEST. [AESCHBACHER HU ET AL; NONMUTAGENICITY IN VIVO OF THE FOOD FLAVONOL QUERCETIN; NUTR CANCER 4(2) 90 (1982)]**PEER REVIEWED**
  
• THE GENOTOXICITY OF SELECTED FLAVONOLS WAS STUDIED. CHROMOSOMAL ABERRATIONS, SISTER-CHROMATID EXCHANGE (SCE) & FORWARD MUTATION AT 4 GENE LOCI WERE MEASURED IN A SINGLE POPULATION OF CHINESE HAMSTER OVARY CELLS (CHO) EXPOSED TO QUERCETIN FOR 15 HR WITH & WITHOUT METABOLIC ACTIVATION. INCIDENCE OF CHROMOSOMAL ABERRATIONS WAS SIGNIFICANTLY INCREASED IN THE ABSENCE OF ACTIVATION. FLAVONOL TREATMENT AFFECTED SCE & MUTATION AT THE HGPRT, APRT, OR NA+/K+-ATPASE LOCI ONLY MARGINALLY, BUT SIGNIFICANTLY INCREASED MUTATION FREQUENCIES AT THE TK LOCUS. THE RESPONSE AT THE TK LOCUS SUGGESTS THAT THE CHO CELLS MAY BEHAVE SIMILARLY TO L5178Y CELLS, IN WHICH THE TK LOCUS IS THOUGHT TO REFLECT CHROMOSOMAL LESIONS IN ADDITION TO POINT MUTATION. THESE EXPERIMENTS INDICATE THAT, AT LEAST UNDER THESE CONDITIONS EXAMINED, FLAVONOLS INDUCE CHROMOSOMAL ABERRATIONS IN CHO CELLS, BUT HAVE LITTLE EFFECT ON POINT MUTATION OR SCE. [CARVER JH ET AL; GENETIC EFFECTS OF THE FLAVONOLS QUERCETIN, KAEMPFEROL, AND GALANGIN ON CHINESE HAMSTER OVARY CELLS IN VITRO; MUTAT RES 113(1) 45 (1983)]**PEER REVIEWED**
  
• RATS WERE MAINTAINED ON A DIET CONTAINING 1 0R 5% QUERCETIN FOR 540 DAYS, OR 10% FOR 850 DAYS. MOST TUMORS FOUND IN EXPERIMENTAL GROUPS WERE ALSO FOUND IN THE CONTROL GROUPS. THERE WAS NO SIGNIFICANT DIFFERENCE BETWEEN THE INCIDENCE OF TUMORS IN THE EXPERIMENTAL OR CONTROL GROUPS (P= 0.05). QUERCETIN WAS NOT CARCINOGENIC TO ACI RATS. [HIRONO I ET AL; CARCINOGENICITY EXAMINATION OF QUERCETIN AND RUTIN IN ACI RATS; CANCER LETT 13(1) 15 (1981)]**PEER REVIEWED**
  
• QUERCETIN WAS ACTIVE IN THE MOUSE LYMPHOMA TK+/- MUTATION ASSAY, INCREASING THE FREQUENCY OF TFT-RESISTANT COLONIES FROM A CONTROL VALUE OF 37/106 VIABLE CELLS TO 355/106 VIABLE CELLS AT 20 MUG/ML. WHEN S9 WAS PRESENT, THE ACTIVITY WAS DECREASED AT EACH CONCN USED. AS THE S9 CONCN EMPLOYED DECREASED, THE INDUCED MUTANT FREQUENCY INCREASED. DNA SINGLE-STRAND BREAKAGE WAS OBSERVED WITHOUT S9 AT 10 MUG/ML, USING THE ALKALINE ELUTION TECHNIQUE; A MAXIMAL RATE OF ELUTION WAS REACHED AT 20 MUG/L. IN THE BALB/C 3T3 CHEMICAL TRANSFORMATION EXPERIMENTS, TRANSFORMATION JUST AT THE LEVEL OF 0.05% (IF BOTH INTERMEDIATE & TYPICAL TRANSFORMED COLONIES WERE COMBINED) WAS OBSERVED. [MELTZ ML, MACGREGOR JT; ACTIVITY OF THE PLANT FLAVONOL QUERCETIN IN THE MOUSE LYMPHOMA L5178Y TK+/- MUTATION, DNA SINGLE-STRAND BREAK AND BALB/C 3T3 CHEMICAL TRANSFORMATION ASSAYS; MUTAT RES 88(3) 317 (1981)]**PEER REVIEWED**
  
• QUERCETIN WAS TESTED FOR CARCINOGENICITY IN NON-INBRED GOLDEN HAMSTERS. IN EXPERIMENT I, 10% QUERCETIN OR CONTROL DIET WAS ADMIN FOR 735 DAYS. TUMORS APPEARED MAINLY IN THE FORESTOMACH, BUT WAS NOT STATISTICALLY DIFFERENT AMONG THE GROUPS. IN EXPERIMENT II, ONE GROUP WAS ADMIN 4% FOR 709 DAYS. GROUP 2 WAS GIVEN 1% IN DIET FOR 351 DAYS & THEN THE BASAL DIET FOR 350 DAYS. GROUP 3 RECEIVED 1% QUERCETIN DIET & THE 1% CROTON OIL DIET & GROUP 4 WAS GIVEN BASAL DIET FOLLOWED BY 1% CROTON OIL, FOR SAME PERIODS AS GROUP 2. GROUP 5 WAS GIVEN BASAL DIET FOR 701 DAYS. THERE WAS NO STATISTICAL DIFFERENCES AMONG EXPERIMENTAL GROUPS & RESPECTIVE CONTROLS. [MORINO K ET AL; CARCINOGENICITY TEST OF QUERCETIN AND RUTIN IN GOLDEN HAMSTERS BY ORAL ADMINISTRATION; CARCINOGENESIS 3(1) 93 (1982)]**PEER REVIEWED**
  
• QUERCETIN (50, 100, OR 150 MG/KG, ORALLY) FAILED TO INDUCE MUTATION IN THE GERM CELLS OF MICE USING THE SPERM ABNORMALITY ASSAY. [NANDAN SD, RAO MS; LACK OF MUTAGENIC EFFECTS OF QUERCETIN IN THE GERM CELLS OF MICE; IRCS MED SCI COMPEND 11(3) 210 (1983)]**PEER REVIEWED**
  
• QUERCETIN WAS NEGATIVE IN BACILLUS SUBTILIS. [SACKS LE, MACGREGOR JT; THE B SUBTILIS MULTIGENE SPORULATION TEST FOR MUTAGENS: DETECTION OF MUTAGENS INACTIVE IN THE SALMONELLA HIS REVERSION TEST; MUTAT RES 95(2-3) 191 (1982)]**PEER REVIEWED**
  
• FOUR FLAVONOID COMPOUNDS, QUERCETIN, KAEMPFEROL, NEOHESPERIDIN DIHYDROCHALCONE, & RUTIN, WERE ADMINISTERED TO MALE MICE FOR DETECTION OF GROSS CHROMOSOMAL ANOMALIES BY THE MICRONUCLEUS TEST. THE FIRST 3 COMPOUNDS WERE POSITIVELY CLASTOGENIC TO DIFFERENT EXTENTS, WHEREAS THE 4TH WAS NEGATIVE. [SAHU RK ET AL; GENETIC TOXICOLOGICAL TESTING OF SOME PLANT FLAVONOIDS BY THE MICRONUCLEUS TEST; MUTAT RES 89(1) 69 (1981)]**PEER REVIEWED**
  
• GROUPS OF 38 MALE & 35 FEMALE DDY MICE, SIX-WEEKS OLD, WERE GIVEN PELLETS CONTAINING 2% QUERCETIN THROUGHOUT THEIR LIFE SPAN. AS CONTROLS, 16 MALES & 15 FEMALES WERE GIVEN BASAL DIET. ANIMALS IN THE EXPERIMENTAL & CONTROL GROUPS DEVELOPED LEUKEMIA & TUMORS OF THE LUNG, FORESTOMACH, MAMMARY GLAND, ADRENAL & SOFT PART TISSUES. IN ADDITION, SOME ANIMALS IN TREATED GROUPS DEVELOPED TUMORS OF THE HEART, LIVER, SALIVARY GLAND, OVARY, & UTERUS. THE INCIDENCES OF THESE TUMORS IN TEST & CONTROL GROUPS WERE NOT STATISTICALLY DIFFERENT. [SAITO D ET AL; TEST OF CARCINOGENICITY OF QUERCETIN, A WIDELY DISTRIBUTED MUTAGEN IN FOOD; TERATOGENESIS CARCINOG MUTAGEN 1(2) 213 (1980)]**PEER REVIEWED**
  
• TWO OF THE FLAVONOLS FOUND IN FOODS, QUERCETIN & KAEMPFEROL, WERE MUTAGENIC AS MEASURED BY THE RECESSIVE SEX-LINKED LETHAL TEST. SINCE DROSOPHILA APPEARS TO POSSESS METABOLIZING CAPACITIES SIMILAR TO THOSE OF MAMMALS, THERE IS CLEARLY A POTENTIAL HAZARD THAT THESE FLAVONOLS MAY BE CARCINOGENIC TO MAN. [WATSON WA F; THE MUTAGENIC ACTIVITY OF QUERCETIN AND KAEMPFEROL IN DROSOPHILA MELANOGASTER; MUTAT RES 103(2) 145 (1982)]**PEER REVIEWED**
  
• SINGLE ORAL DOSE OF 2, 20, 200 OR 2000 MG QUERCETIN/KG WAS ADMIN TO RATS ON THE MORNING OF DAY 9 OF GESTATION. OTHER PREGNANT RATS RECEIVED SIMILAR DOSES DAILY, ON DAYS 6-15 OF GESTATION. SOME TREATED GROUPS SHOWED A SIGNIFICANT DECREASE IN AVG WEIGHT OF DAY-20 FETUSES COMPARED WITH CONTROLS. HOWEVER, STUDIES OF FETUSES RECOVERED ON DAY 20 OF GESTATION FAILED TO SHOW ANY REPRODUCIBLE DOSE-RELATED SYNDROME OF TERATOGENIC EFFECTS ATTRIBUTABLE TO QUERCETIN TREATMENT. [WILLHITE CC; TERATOGENIC POTENTIAL OF QUERCETIN IN THE RAT; FOOD CHEM TOXICOL 20(1) 75 (1982)]**PEER REVIEWED**
  
• QUERCETIN INDUCED CHROMOSOME ABERRATIONS & SISTER CHROMATID EXCHANGE (SCE) IN HAMSTER CELLS (FIBROBLASTS & LYMPHOCYTES) WITHOUT METABOLIC ACTIVATION. THE INCREMENT IN FREQUENCY OF SCE WAS DOSE-DEPENDENT & MAX FREQUENCY WAS 1.7-3.3-FOLD GREATER THAN THAT OF THE CONTROL VALUES. THE FREQUENCY OF CHROMOSOME ABERRATIONS WAS ELEVATED 1.7-7.8-FOLD COMPARED WITH CONTROLS. [YOSHIDA MA ET AL; CYTOGENETIC EFFECTS OF QUERCETIN ON CULTURED MAMMALIAN CELLS; PRC JPN ACAD, SER B 56(7) 443 (1980)]**PEER REVIEWED**
  
• .... Conclusions Under the conditions of these 2 year feed studies there was some evidence of carcinogenic activity of quercetin in male F344/N rats based on an increased incidence of renal tubule cell adenomas. There was no ev dence of carcinogenic activity of quercetin in female F344/N rats receiving 1,000, 10,000 or 40,000 ppm. [Toxicology & Carcinogenesis Studies of Quercetin in F344/N Rats (Feed Studies). Technical Report Series No. 409 (1992) NIH Publication No. 92-3140 U.S. Department of Health and Human Services, National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709]**QC REVIEWED**
  

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Human Toxicity Values

• None found

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Non-Human Toxicity Values

• None found

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Absorption, Distribution and Excretion

• WHEN (14)C-QUERCETIN WAS ADMIN ORALLY TO ACI RATS, ABOUT 20% OF THE ADMIN DOSE WAS ABSORBED FROM DIGESTIVE TRACT, MORE THAN 30% WAS DECOMPOSED TO YIELD (14)CO2 & ABOUT 30% WAS EXCRETED UNCHANGED IN FECES. [UENO K ET AL; METABOLIC FATE OF (14)C-QUERCETIN IN THE ACI RAT; JPN J EXP MED 53(1) 41 (1983)]**QC REVIEWED**
  

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Metabolism/Metabolites

• THE GLYCOSIDES ARE HYDROLYZED IN THE BODY TO CORRESPONDING AGLYCONES, WHICH ARE THEN FURTHER METABOLIZED BY SCISSION OF THE HETEROCYCLIC RING TO GIVE 3,4-DIHYDROXY-PHENYL-SUBSTITUTED ACIDS... THE SITE OF RING SCISSION DEPENDS ON STRUCTURE. ... WITH FLAVONOLS (QUERCETIN) SCISSION OCCURS AT THE 1,2 & 3,4 BONDS TO YIELD HOMOPROTOCATECHUIC ACID... THESE ACIDS ARE FURTHER METABOLIZED BY BETA-OXIDATION OF ACYL SIDE-CHAIN, O-METHYLATION & DEMETHYLATION, & AROMATIC DEHYDROXYLATION. [Parke, D. V. The Biochemistry of Foreign Compounds. Oxford: Pergamon Press, 1968., p. 151]**PEER REVIEWED**
  
• YIELDS DIHYDROQUERCETIN PROBABLY IN CICER: HOSEL W, BARZ W; BIOCHIM BIOPHYS ACTA; 261: 294 (1972); YIELDS 3,4-DIHYDROXYPHENYLHYDRACRYLIC ACID PROBABLY IN PIG: KALLIANOS AG ET AL; ARCHS BIOCHEM BIOPHYS 81: 430 (1959); YIELDS 3,4-DIHYDROXYPHENYLACETIC ACID IN RABBIT: MURRAY CW ET AL; J AM PHARM ASS 43: 361 (1950); YIELDS 3',7-DIMETHYLQUERCETIN IN ASPERGILLUS: HALUK JP, METCHE M; BULL SOC CHIM BIOL 52: 667 (1970); YIELDS M-HYDROXYPHENYLPROPIONIC ACID & M-HYDROXYPHENYLACETIC ACID IN MICROORGANISM: SCHELINE RR; ACTA PHARMAC TOX 26: 332 (1968); YIELDS ISORHAMNETIN IN PARSLEY: EBEL J ET AL; BIOCHIM BIOPHYS ACTA 269: 313 (1972); YIELDS PHLOROGLUCINOLCARBOXYLIC ACID IN RAT: KALLIANOS AG ET AL; ARCH S BIOCHEM BIOPHYS 81: 430 (1959); YIELDS PROTOCATECHUOYLPHLOROGLUCINOLCARBOXYLIC ACID IN ASPERGILLUS: OKA T ET AL; CAN J MICROBIOL 18: 493 (1972). /FROM TABLE/ [Goodwin, B.L. Handbook of Intermediary Metabolism of Aromatic Compounds. New York: Wiley, 1976., p. Q-1]**PEER REVIEWED**
  
• O-BETA-HYDROXYETHYLATED DERIVATIVES OF QUERCETIN WERE ISOLATED FROM URINE SAMPLES & SEPARATED BY HPLC. THE 5,7,3',4'-TETRA COMPD WAS SEPARATED FROM 3,7,3',4'-TETRA DERIVATIVE. THE 7,3',4'-TRI & 7'-MONO COMPOUNDS GAVE 1 COMMON PEAK, SEPARATED FROM THE PEAK FOR THE 7,4'-DI COMPD. [KUHNZ W ET AL; QUANTITATIVE DETERMINATION OF O-(BETA-HYDROXYETHYL)QUERCETINS IN URINE BY HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; STUD ORG CHEM (AMSTERDAM) 11(FLAVONOIDS BIOFLAVONOIDS) 293 (1982)]**PEER REVIEWED**
  
• AFTER ORAL ADMIN TO ACI RATS, THE ABSORBED (14)C-QUERCETIN WAS RAPIDLY EXCRETED INTO THE BILE & URINE WITHIN 48 HR AS THE GLUCURONIDE & SULFATE CONJUGATES OF (14)C-QUERCETIN, 3'-O-MONOMETHYL QUERCETIN & 4'-O-MONOMETHYL QUERCETIN. EFFICIENT METABOLISM AND ELIMINATION OF QUERCETIN MAY BE ONE REASON FOR THE LACK OF CARCINOGENICITY IN RATS [UENO K ET AL; METABOLIC FATE OF (14)C-QUERCETIN IN THE ACI RAT; JPN J EXP MED 53(1) 41 (1983)]**QC REVIEWED**
  

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TSCA Test Submissions

• None found

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Footnotes

¹ Source: the National Library of Medicine's Hazardous Substance Database, 10/28/2007.