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At least 19 recordsLinked to original sources
PubMed1979

Studies of the biliary excretion and metabolites of the antioxidant ethoxyquin, 6-ethoxy-2,2,4-trimethyl-1,2-dihydroquinoline in the rat.

1. Biliary excretion and metabolites of ethoxyquin, and gastro-intestinal absorption of ethoxyquin were studied in rat. 2. An average of 28 and 36% of the dose of 14C following intragastric administration of [14C]ethoxyquin was recovered in the bile of bile-duct cannulated rats in 12 and 24 h, respectively. 3. By g.l.c.-mass spectrometry, 75 to 85% of the 14C excreted in the 12 h bile was identified as unchanged ethoxyquin, and the following metabolites were isolated and identified: 8-hydroxy-ethoxyquin, hydroxylated 8-hydroxy-ethoxyquin, 6-ethoxy-2,2,4-trimethyl-8-quinolone, hydroxylated 6-ethoxy-2,2,4-trimethyl-8-quinolone, 6-ethoxy-2,4-dimethylquinoline and 2,2,4-trimethyl-6-quinolone. 4. Three groups of rats were used in the biliary excretion experiments, and the effect of standardization of experimental conditions was demonstrated. Infusion of sodium taurocholate following bile-duct cannulation did not affect the biliary excretion kinetics of ethoxyquin. 5. Only about 3% of the radioactivity administered was absorbed from the gastrointestinal tract via the lymphatic pathway in thoracic-duct connulated rats within 24 h. It was concluded that ethoxyquin was absorbed primarily by the portal route.

Adsorption↗
PubMed1996

The effect of ethoxyquin on tissue peroxidation and immune status of single comb White Leghorn cockerels.

The responses to supplementing the diet of Single Comb White Leghorn (SCWL) cockerels with ethoxyquin were tested on two parameters: 1) tissue peroxidation and 2) immune response. In the first experiment, three concentrations of supplemental ethoxyquin (0, 500, and 1,000 ppm) were added to a basal diet and fed to SCWL cockerels for 6 wk. Tissue peroxidation was assessed by measuring the thiobarbituric acid reactive substances (TBARS) concentration in the liver, kidney, heart, and spleen. The TBARS concentration in response to 500 ppm dietary ethoxyquin was significantly lower in the liver and spleen tissues, whereas in the kidneys, 1,000 ppm ethoxyquin significantly lowered TBARS. In a second experiment, four concentrations of ethoxyquin (0, 125, 500, and 1,000 ppm) were added to a basal diet and fed to SCWL cockerels for 8 wk. The primary and secondary immune response were assessed by determining antibody titers to the Newcastle disease virus using hemagglutination inhibition (HI) and ELISA. The HI and ELISA titers for the primary and secondary immune response were not significantly different from the control. Analysis of body weight, feed conversion, and organ weight revealed no statistically significant differences between treatments, although in the second experiment the dietary treatment of 1,000 ppm ethoxyquin resulted in significantly higher relative liver weight.

Analysis of Variance↗
PubMed1992

Sequential study of the chronic nephrotoxicity induced by dietary administration of ethoxyquin in Fischer 344 rats.

Groups of 3-week-old male and female Fischer 344 rats were administered 0.5% ethoxyquin-containing diet for varying periods of time, ranging from 4 weeks up to 18 months, to assess renal histopathology. The primary lesion observed was renal papillary necrosis in the male rat, commencing as interstitial degeneration of the papillary tip by 4 weeks exposure, and reaching a complete form of papillary necrosis by 24 weeks. The papillary necrosis in male rats was consistently accompanied by active pyelonephritis affecting the cortex, and urothelial hyperplasia in the renal pelvis. A marked sex difference was evident in that female rats developed papillary change at a later stage than males and the lesion never progressed beyond interstitial degeneration. A further sex difference associated with ethoxyquin treatment was the increasing cellular accumulation of lipofuscin-related pigment involving proximal tubules in female rats. Spontaneous chronic progressive nephropathy (CPN) was exacerbated by ethoxyquin in both males and females, but more so in the former. Proximal tubule hyperplasia was most frequently observed in ethoxyquin-treated males at the later sampling times. In all cases, such proliferative lesions were associated either with pyelonephritis or with the most advanced stages of CPN. Contrary to a previous report, there was no evidence that ethoxyquin directly induced preneoplastic renal tubule hyperplasia.

Animals↗
PubMed1991

Ethoxyquin-induced resistance to aflatoxin B1 in the rat is associated with the expression of a novel alpha-class glutathione S-transferase subunit, Yc2, which possesses high catalytic activity for aflatoxin B1-8,9-epoxide.

A purification scheme has been devised for two ethoxyquin-inducible Alpha-class glutathione S-transferases (GSTs) which possess at least 25-fold greater activity towards aflatoxin B1 (AFB1)-8,9-epoxide than that exhibited by the GSTs (i.e. F, L, B and AA) that have been described previously. These two enzymes are both heterodimers and both contain a subunit of Mr 25,800. This subunit has been isolated from both of the GST isoenzymes and, after cleavage with CNBr, it has been subjected to automated amino acid sequencing. The primary structure of the Mr 25,800 subunit revealed that it forms part of a subfamily of Alpha-class GSTs which possess closest identity (about 92%) with the Yc subunit of apparent Mr 27,500, which is encoded by the recombinant cDNA clone pGTB42 [Telakowski-Hopkins, Rodkey, Bennett, Lu & Pickett (1985) J. Biol. Chem. 260, 5820-5825]. As these two GSTs possess less than 70% sequence identity with the Ya1 and Ya2 subunits, both of Mr 25,500, the constitutively expressed Yc subunit of Mr 27,500 has been renamed Yc1 and the ethoxyquin-inducible GST of Mr 25,800 has been designated Yc2. Using this nomenclature, the two GSTs with high activity for AFB1-8,9-epoxide are Ya1Yc2 and Yc1Yc2. Although evidence suggests that induction of Yc2 is responsible for the high detoxification capacity of livers from ethoxyquin-treated rats for AFB1-8,9-epoxide, resistance towards AFB1 may be multifactorial in this instance as dietary ethoxyquin also induces the Ya1, Ya2 and Yc1 subunits about 2.2-, 10.9- and 2.7-fold respectively. Besides the induction of GST by ethoxyquin, activity towards AFB1-8,9-epoxide is also elevated in the livers of neonatal rats and in livers that contain preneoplastic nodules. Western blotting experiments show that Yc2 is not present in hepatic cytosol from adult rats fed on normal diets but is expressed in neonatal rat livers and in the livers of adult rats that contain preneoplastic nodules that have arisen as a consequence of consuming diets contaminated with AFB1.

Aflatoxin B1↗
PubMed1995

The influence of dietary ethoxyquin on the vitamin E status in broilers.

In a feeding experiment with 48 male broiler chickens was the effect of dietary ethoxyquin and dl-alpha-tocopherol acetate on vitamin E status of chickens investigated. The experimental diets were offered the chickens from the first day of age until the end of the experiment at 42 days. Chickens were fed on diets containing 0, 75, or 150 mg ethoxyquin/kg feed, with (30 mg/kg feed) or without added dl-alpha-tocopherol acetate. The concentration of alpha-tocopherol in plasma of chickens on dl-alpha-tocopherol acetate supplemented diets were significantly higher than those of chickens fed on the nonsupplemented diets. Supplementation with alpha-tocopherol acetate reduced the haemolysis in vitro. Ethoxyquin seemed to have an increasing effect on the concentration of alpha-tocopherol in plasma, but not in the liver. Addition of ethoxyquin to diets without dl-tocopherol acetate reduced the concentration of gamma-tocopherol in plasma. Significant interactions between the addition of ethoxyquin and the addition of dl-alpha-tocopherol acetate to the feed were observed on the haemolysis in vitro and the activity of glutathione peroxidase in plasma. The results indicate that incorporation of ethoxyquin in the diets of chickens exert an improving effect on the vitamin E status of the organism.

Analysis of Variance↗
PubMed1988

Effects of ethoxyquin feed preservative and peroxide level on broiler performance.

Rancidity development in feeds and feed ingredients reduces the feeds' nutritive value and produces toxic peroxides. This investigation was conducted to determine the effects of different levels of peroxide on broiler performance and to determine the effectiveness of ethoxyquin in ameliorating the adverse effects of peroxides. Poultry fat was oxidized to contain 0, 50, 100, and 175 meq peroxide/kg and added to diets to provide 0, 2, 4, or 7 meq peroxide/kg feed, respectively. Liquid ethoxyquin was incorporated into the diets at 0, 62.5, and 125 ppm. Each of the 12 diets was fed to 8 replicate pens with 35 males and 35 females/pen. Body weights at 21 and 42 days of age were significantly lower in birds fed diets containing 4 or 7 meq peroxide/kg feed. At 49 days of age, the reduction in body weight was significant only at the 7 meq/kg level. Reductions in feed efficiency showed a similar pattern, but the depression was significant only at the highest peroxide level. Supplementation of 62.5 and 125 ppm ethoxyquin resulted in significantly heavier birds at 49 days of age but had no significant effect on feed efficiency. Beneficial effects of ethoxyquin supplementation were evident at higher peroxide levels. The study showed that at least 4 meq peroxide/kg feed was required to significantly affect bird performance, and that the addition of ethoxyquin could alleviate the deleterious effects of dietary peroxide.

Animal Feed↗
PubMed1986

Inhibitory effects of ethoxyquin, 4,4'-diaminodiphenylmethane and acetaminophen on rat hepatocarcinogenesis.

Four antioxidant species, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), ethoxyquin and alpha-tocopherol, and three other compounds, 4,4'-diaminodiphenylmethane (DDPM), acetaminophen and glutathione, were tested for inhibitory effect on hepatocarcinogenesis in male F344 rats. Rats were initially given a single ip injection of diethylnitrosamine (200 mg/kg body weight) and fed basal diet containing 0.02% 2-acetylaminofluorene from week 2 to week 8. Animals were subjected to partial hepatectomy at the end of week 3. From week 12 to week 36, they were given basal diet containing 2% BHA, 1% BHT, 0.8% ethoxyquin, 1% alpha-tocopherol, 0.1% DDPM, 1% acetaminophen, or 1% glutathione, then killed at week 40, 4 weeks after cessation of treatment with the test chemicals. The incidence of hepatocellular carcinoma (HCC) was significantly decreased in the groups given ethoxyquin or DDPM. Quantitative analysis of the number and area of HCC per unit liver area revealed a significant decrease in the area of HCC in the groups given ethoxyquin, DDPM or acetaminophen. The results suggest that ethoxyquin, DDPM and acetaminophen exerted an inhibitory effect on the development of HCC, while BHA, BHT, alpha-tocopherol and glutathione had no significant effect.

2-Acetylaminofluorene↗
PubMedDate not supplied

Ability of ethoxyquin and butylated hydroxytoluene to counteract deleterious effects of dietary aflatoxin in chicks.

The antioxidants ethoxyquin and butylated hydroxytoluene (BHT) were added to diets of chicks in concentrations three and eight times above that usually found in poultry feed beginning 15 days after hatch; the chicks had been placed on feed containing 1000 or 3000 ppb aflatoxin on the day of hatch. These diets were continued until chicks were 6 weeks of age. At that time, deleterious effects of aflatoxin on weight gain, feed efficiency, and organ weights (spleen, bursa) were evident. BHT alleviated these effects, but ethoxyquin did not. Pretreatment with ethoxyquin did not protect chicks either. Ethoxyquin was not able to induce the activities of chick liver enzymes that detoxify aflatoxin and other foreign compounds. Lack of effect of ethoxyquin on these enzymes may hinder ability of this antioxidant to protect chicks from aflatoxin.

Aflatoxins↗
PubMed1981

Effect of oxidized fish oil, DL-alpha-tocopheryl acetate and ethoxyquin supplementation on the vitamin E nutrition of rainbow trout (Salmo gairdneri) fed practical diets.

A factorial experiment was conducted using two degrees of oxidation of the 7.5% supplemental fish oil (peroxide values of 5 and 120 meq/kg oil), two levels of supplemental DL-apha-tocopheryl acetate (0 and 33 mg/kg diet) and two levels of ethoxyquin (0 and 125 mg/kg diet) supplementation. Dietary thiobarbituric acid number, weight percentage of polyunsaturated fatty acids and omega-three fatty acids in the total fatty acids were significantly (P less than 0.05) different between diets with fresh and highly oxidized oil. Dietary RRR-alpha-tocopherol was significantly (P less than 0.05) reduced by the addition of highly oxidized oil after 24 weeks storage of the feed while supplemental DL-alpha-tocopheryl acetate level was not changed. Fish fed the various diets showed no differences in growth, feed:gain ratio, carcass composition or plasma glutathione peroxidase activity. The mortality, percent red cells hemolyzed by hydrogen peroxide, plasma and liver RRR-alpha-tocopherol concentrations were significantly (P less than 0.05) affected by the addition of highly oxidized oil or DL-alpha-tocopheryl acetate but not by ethoxyquin except that mortality was reduced by supplementary ethoxyquin. The results of this study suggested that no vitamin E or ethoxyquin supplementation was needed to prevent a deficiency of vitamin E in rainbow trout fed a practical diet containing 7.5% of a good quality herring oil for 24 weeks.

Animal Nutritional Physiological Phenomena↗
PubMed1996

Comparative metabolism and disposition of ethoxyquin in rat and mouse. II. Metabolism.

1. The major pathways of ethoxyquin (EQ) metabolism in both the rat and mouse are O-deethylation and conjugation to endogenous substrates. 2. The two major EQ-derived metabolites excreted in rat urine were in the form of sulphate conjugates, 1,2-dihydro-6-hydroxy-2,2,4-trimethylquinoline sulphate, and 1,2,3,4-tetrahydro-3,6-dihydroxy-4-methylene-2,2-dimethylquinoline sulphate. The latter apparently arises from an intramolecular rearrangement of the 3,4-epoxide of ethoxyquin. 3. Mouse urine contained one major glucuronide, 1,2-dihydro-6-hydroxy-2,2,4-trimethylquinoline glucuronide as well as one major sulphate conjugate, 1,2-dihydro-6-hydroxy-2,2,4-trimethylquinoline sulphate. 4. EQ-derived radioactivity was excreted in rat bile, mainly as GSH conjugates, with little unchanged EQ present. Two of the biliary metabolites are glutathione conjugates of ethoxyquin 3,4-epoxide; the third appears to be a conjugate of either ethoxyquin 7,8-epoxide or 2,2,4-trimethylquinol-6-one.

Animals↗
PubMed1978

Influence of ethoxyquin on the utilization of selenium by the chick.

Experiments showed that commonly used concentrations of dietary ethoxyquin (6-ethoxy-2,2,4-trimethyl-1,2-dihydroxyquinoline) spare the selenium requirement of the vitamin E-deficient chick according to the following function: log Y = -0.0011X - 0.7741, where Y = Se requirement (ppm) and X = dietary ethoxyquin (ppm). The basis of the sparing effect appeared to be metabolic; (a) ethoxyquin was effective in alleviating exudative diathesis when fed (physiologically and chronologically) separately from selenium, and (b) ethoxyquin was effective in promoting increases in the plasma of the selenium-containing enzyme, glutathione peroxidase.

Animals↗
PubMed1983

Reverse phase high pressure liquid chromatography and fluorescence detection of ethoxyquin in milk.

A high pressure liquid chromatographic (HPLC) method has been developed for the determination of ethoxyquin (1,2-dihydro-6-ethoxy-2,2,4-trimethyl-quinoline) in milk. Milk solids are precipitated by adding acetonitrile, and the water-acetonitrile supernate is washed with hexane to remove fat. Addition of sodium chloride causes the water-acetonitrile solution to separate into an aqueous phase and an acetonitrile phase, thus separating ethoxyquin from most water-soluble impurities. A large volume of water is then added to the acetonitrile layer and ethoxyquin is partitioned into hexane, which is removed at reduced pressure. The residue is dissolved in the mobile phase and analyzed on a 4.6 mm id X 250 mm Ultrasphere ODS column using fluorescence detection (excitation 230 nm; 418 nm cutoff filter). Water-acetonitrile with a diethylamine-acetic acid buffer is the mobile phase. Recoveries from samples fortified at 1, 5, and 10 ppb averaged 78% with a coefficient of variation of 5.0%. Low levels (less than 1 ppb) of apparent ethoxyquin were found in commercial milk samples that were analyzed by using the method.

Animals↗
PubMed1984

Inhibitory effect of antioxidants ethoxyquin and 2(3)-tert-butyl-4-hydroxyanisole on hepatic tumorigenesis in rats fed ciprofibrate, a peroxisome proliferator.

The objective of this study was to test the hypothesis that hepatocarcinogenesis by peroxisome proliferators, a novel class of chemical carcinogens, is mediated either directly by carcinogenic H2O2, generated by peroxisomal oxidase(s) or indirectly by free radicals produced from H2O2, and that antioxidants could retard or inhibit neoplasia by scavenging active oxygen (super-oxide radicals O(2), hydrogen peroxide, hydroxyl radicals HO, and singlet oxygen 1O2). Accordingly, the effect of synthetic antioxidants 2(3)-tert-butyl-14-hydroxyanisole and ethoxyquin on the peroxisome proliferator 2-[4-(2,2-dichlorocyclopropyl)phenoxy]2-methyl-propionic acid (ciprofibrate)-induced hepatic tumorigenesis has been examined in male Fischer 344 rats. Rats were fed either a 2(3)-tert-butyl-4-hydroxyanisole (0.5% w/w)- or ethoxyquin (0.5% w/w)-containing diet with or without ciprofibrate (10 mg/kg of body weight) for 60 weeks. Rats fed ciprofibrate (10 mg/kg of body weight) in the diet or fed a diet with no added chemicals served as controls. Results of this study demonstrated that ethoxyquin markedly inhibited the hepatic tumorigenic effect of ciprofibrate, as evidenced by a decreased incidence of tumors, a decreased number of tumors per liver, and a reduced tumor size. 2(3)-tert-Butyl-4-hydroxyanisole also caused a significant decrease in the incidence and number of hepatocellular carcinomas that were larger than 5 mm. The present data suggest that the inhibitory effect of antioxidants on ciprofibrate-induced hepatic tumorigenesis may be due to H2O2 and free radical-scavenging property of ethoxyquin and 2(3)-tert-butyl-4-hydroxyanisole, since these antioxidants do not prevent peroxisome proliferation and induction of H2O2-generating peroxisomal enzymes in livers of rats fed ciprofibrate. Whether the inhibitory effect of antioxidants is exercised on the presumptive H2O2 initiation process and/or on the postinitiation growth phase of foci and nodules in liver is, at present, unknown.

Animals↗
PubMed1981

High pressure liquid chromatographic determination of ethoxyquin in paprika and chili powder.

A method is described for the determination of ethoxyquin (1,2-dihydro-6-ethoxy-2,2,4-trimethylquinoline) in paprika and chili powder. Ethoxyquin is extracted from the spice with hexane and partitioned into 0.3N HCl. After adjusting the solution to pH 13-14, ethoxyquin is extracted into hexane, and the hexane layer is evaporated to dryness. An acetonitrile solution of the residue is then analyzed by reverse phase high pressure liquid chromatography with detection at 254 nm. The mobile phase is water-acetonitrile with ammonium acetate buffer. Recoveries from samples fortified at 50, 100, and 200 ppm averaged 92% with a coefficient of variation of 2.3%. The method was applied to a number of commercial samples of paprika and chili powder. Ethoxyquin was found in paprika samples at levels up to 63 ppm and in chili powder samples at levels up to 20 ppm.

Capsicum↗
PubMedDate not supplied

Determination of ethoxyquin in feeds by liquid chromatography: collaborative study.

Ethoxyquin is a chemical antioxidant used in feeds, ingredients, fats, and oils. A liquid chromatographic (LC) method for determination of ethoxyquin was developed. The method involves acetonitrile extraction of the sample and isocratic C18 reversed-phase chromatography with ammonium acetate buffer-acetonitrile as mobile phase and fluorescence detection. A collaborative study of the determination of ethoxyquin in various meals and extruded pet foods was conducted by The Iams Company Research Laboratory. Eleven laboratories analyzed 16 samples (including 2 blind duplicates) consisting of 7 meat meals and 9 extruded pet foods. Sample means ranged from 0.25 to 289 ppm. Repeatability standard deviations ranged from 0.08 to 3.2 ppm, and repeatability relative standard deviations ranged from 4.5 to 32%. Reproducibility standard deviations ranged from 0.12 to 13 ppm, and reproducibility relative standard deviations ranged from 4.5 to 55%. The LC method for determination of ethoxyquin in feeds has been adopted first action by AOAC INTERNATIONAL.

Acetonitriles↗
PubMed1995

Induction of phase I and phase II drug-metabolizing enzyme mRNA, protein, and activity by BHA, ethoxyquin, and oltipraz.

Various natural and synthetic compounds are known to protect against cancer by elevating phase II detoxification enzymes. Generally classified as monofunctional, these inducers are believed to trigger cellular signal(s) that activate gene transcription through an antioxidant or electrophile response element (ARE/EpRE) in responsive genes. In contrast, the phase I enzymes of drug metabolism (cytochrome P450s) are not believed to be induced by monofunctional inducers and P450 genes have not been found to contain functional ARE/EpREs. In this study, rats were treated with the monofunctional inducers tert-butylated hydroxyanisole, ethoxyquin, and oltipraz to study the inducibility of individual glutathione S-transferase isozymes, NADP(H):quinone oxidoreductase, gamma-glutamylcysteine synthetase, UDP-glucuronosyl transferase, and cytochrome P450 enzymes. Hepatic mRNAs were analyzed on Northern blots using gene-specific oligonucleotide probes for GST Ya1, Ya2, Yc1, Yc2, Yb1, Yb2, and Yf, for UGT 1*06, and for P450 1A1, 1A2, 2B1, 2C11, 3A2, and 4A1. NADP(H):quinone oxidoreductase and gamma-glutamylcysteine synthetase mRNAs were detected using cDNA probes. All the phase II detoxification enzymes analyzed, except GST Yf, were induced by the three monofunctional inducers, suggesting that these genes may be regulated by a mechanism involving an ARE/EpRE element in their promoter region. Interestingly, it was found that ethoxyquin was a particularly good inducer for both members of the P450 2B family, 2B1 and 2B2, and both ethoxyquin and oltipraz were also capable of modestly inducing P450 1A2 and 3A2. Oltipraz was found to slightly induce P450 2B2, but not 2B1, at the dose and time analyzed. Induction of mRNA generally correlated well with induction of protein levels determined by Western blot and/or enzyme activity measurements for selected enzymes. The results of this study suggest that many phase II enzymes may contain ARE/EpRE elements in addition to those confirmed to be regulated by a mechanism involving ARE/EpRE elements. In addition, it was found that several P450 enzymes were induced by monofunctional inducers, suggesting a possibility that some phase I enzymes may also be regulated by a mechanism involving ARE/EpRE elements.

Animals↗
PubMed1984

Promotion by ascorbic acid, sodium erythorbate and ethoxyquin of neoplastic lesions in rats initiated with N-butyl-N-(4-hydroxybutyl) nitrosamine.

The promoting effects of ascorbic acid, sodium erythorbate and ethoxyquin on two-stage urinary bladder carcinogenesis in F344 rats initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) at a dose of 0.05% in the drinking water were examined. Administration of 5% sodium erythorbate in the diet significantly increased the incidences of preneoplastic lesions, papilloma and cancer of the urinary bladder, whereas administration of 5% ascorbic acid in the diet did not. Administration of 0.8% ethoxyquin also increased the incidence of neoplastic lesions. Administrations of 5% sodium L-ascorbate and 5% sodium erythorbate caused increases in the pH, the sodium content and crystals of MgNH4PO4 in the urine. These results show that sodium erythorbate and ethoxyquin promote urinary bladder carcinogenesis, while ascorbic acid does not.

Animals↗
PubMed1987

Dose-dependent effects of butylated hydroxyanisole, butylated hydroxytoluene and ethoxyquin for promotion of bladder carcinogenesis in N-butyl-N-(4-hydroxybutyl)nitrosamine-initiated, unilaterally ureter-ligated rats.

Dose-dependent effects of 3 antioxidants, butylated hydroxyanisole (BHA, 2.0, 1.0 and 0.5%), butylated hydroxytoluene (BHT, 1, 0.5 and 0.25%) and ethoxyquin (0.5, 0.25 and 0.125%) on the development of preneoplastic lesions in the bladder of N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-treated rats were investigated. Feeding of the antioxidants after pretreatment of 0.05% BBN commenced and unilateral ureteric ligation was combined at week 3 of the experiment. Surviving rats were killed at the end of week 24. BHA and BHT, but not ethoxyquin increased dose-dependently the incidence and number of preneoplastic lesions, papillary or nodular hyperplasia of the urinary bladder in rats treated with BBN. Particularly, the incidence and number of PN hyperplasia in rats treated with 2.0% BHA and 1.0% BHT were significantly higher than those of the control group. Thus, promoting activities of BHA and BHT, but not ethoxyquin for the urinary bladder were confirmed in this system of BBN-initiated, unilaterally ureter-ligated rats.

Animals↗