The metabolism of butylated hydroxyanisole in the rabbit

Dacre, Jack C.; Denz, F. A.; Kennedy, Traci M.

doi:10.1042/bj0640777

Cited by 43 publications

(17 citation statements)

References 11 publications

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“…As for the tert-butyl group, there are some reports on the metabolism of tert-butyl groups of butylated hydroxyanisole (BHA) (Astill et al 1960(Astill et al , 1962Akagi et al 1962;Aoki 1962;Daniel et al 1968). Hydroxylation at the tert-butyl group of BHA was not detectable in the rat, dog (Astill et al 1960(Astill et al , 1962 and rabbit (Dacre et al 1956). Hydroxylation at the tert-butyl group of butylated hydroxytoluene (BHT) was also not found in the rat and man (Dacre 1961;Akagi et al 1962).…”

Section: Discussionmentioning

confidence: 90%

Distribution, metabolism, and excretion of musk xylene in rats

et al. 1991

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Distribution, metabolism and excretion of musk xylene (MX) were investigated in male Wistar rats. Urinary and fecal excretion accounted for 10 and 75% of the dose (70 mg/kg), respectively, on day 7 after orally administration of 3H-MX to rats. Total residue of radioactivity in tissues on day 7 was less than 2.0% of the administered dose. The highest concentration was found in adipose tissue and the second was in liver. Some metabolites of MX were identified using GC-MS and NMR after purification by column or thin layer chromatography of feces, bile and urine extracts. MX, 2-NH2-MX, 2-Ac-MX, 2-NH2-3-CH2OH-MX, and 2-NH2-5-tert-BuOH-MX were found in feces, bile and urine. 4-NH2-MX and metabolite X were found in feces and urine. 4-NH2-3-CH2OH-MX was found in urine. HO-MX was found in bile. The major route of excretion for MX was the feces via bile. The reduction of the 2-nitro group of MX to the amino group was a key step in metabolism. Further metabolism of 2-NH2-MX may proceed by decreased steric hindrance of functional group.

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Section: Discussionmentioning

confidence: 90%

Distribution, metabolism, and excretion of musk xylene in rats

et al. 1991

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“…There were no abnormal histopathological changes associated with the increase in relative weight of the liver. Dacre et al (1956) and Dacre (1957) have shown tliat BHA and BHT are to some extent excreted as glucuronides and ethereal sulphates. It is probable that the detoxication of these phenols occurs in the liver, and that the hypoplasia of the liver represents an attempt on the part of this organ to meet the stresses placed upon it by the ingestion of these unphysiological substances.…”

Section: Discussionmentioning

confidence: 99%

“…Tlie localization of the loss of hair to the top of the head, except with a few animals on the top concentration of BHT, suggests an endocrine effect although Cunlia et al (1943) have shown that the loss of hair caused by inositol deficiency started in this position and tlien proceeded down the flanks. A possibility that cannot be excluded at this stage is that the loss of hair might be a secondary effect due to a partial sulphur deficiency caused by the excretion of ethereal sulphates, one of the products of detoxication of BHT (Dacre, 1957). The ethereal sulphate production might interfere with cystine metabolism which is of importance in tlie development of hair.…”

Section: Discussionmentioning

confidence: 99%

The Effect of the Level of Dietary Fat on the Toxicity of Phenolic Antioxidants

Brown

Johnson

O'Halloran

1959

Aust J Exp Biol Med

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SUMMARY A study was made of the effect of two antioxidants, butylated hydroxy anisole (BHA) and butylated hydroxy toluene (BHT), with variation in the type and quantity of dietary fat, on growth, food consumption, reproduction, mortality, organ weights and post‐mortem pathology of the rat. The normal cellular behaviour of experimental animals fed diets containing one hundred times the amount of the antioxidant normally expected to be present in human foods (normal testing dose, NTD), is the conventional yardstick of non‐toxicity. The NTD of BHA produced no apparent changes in any of the parameters measured. When BHT was fed at a dietary level of 0·1 p.c. (the NTD) in conjunction with a 20 p.c. lard supplement, it significantly reduced the initial growth rate and mature weight of male rats. No such significant effect was noted in female rats or in male rats with a 10 p.c. lard supplement. A paired feeding experiment showed that this inhibition of growth was a direct toxic effect of BHT and could not be explained by a reduction in the palatability of the diet. At the NTD, BHT produced a significant increase in the weight of the liver relative to the body weight. The mean absolute weight of the liver was also increased. A significant loss of hair on the top of the head occurred in animals whose diet contained the NTD of BHT. This effect was only noted in animals under conditions of increased stress and was enhanced by an increase in the lard content of the diet. Anophthalmia occurred in 10 p.c. of the litters born of parents fed BHT. Even when present in the diet at a concentration of 0·5 p.c., BHA and BHT had no effect on one reproductive cycle of the rat, or the histology of the spleen, kidney, liver, testes or skin, or the ratio to total body weight of the weight of the heart, spleen and kidney. If the conventional NTD be accepted, BHA fulfilled the requirements of non‐toxicity. BHT, at the NTD, on the other hand, produced deleterious deviations from normal cellular behaviour which cast doubt on the advisability of permitting this antioxidant in foodstuffs for human consumption.

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“…Tissue distribution, excretion, metabolism and pharmacokinetic evaluations of BHA have been reported in rat, rabbit, dog and man [9][10][11][12][13]. Urinary excretion of 3H-BHA following i.p.…”

Section: Introductionmentioning

confidence: 99%

Tissue distribution and pharmacokinetics of3H-butylated hydroxyanisole in female mice

1984

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Butylated hydroxyanisole (BHA), a commonly used food additive, is a phenolic antioxidant. While metabolism of BHA has been studied in dog, man, rabbit and rat, information on tissue distribution is limited to rat and dog. Time dependent distribution and elimination of 3H-BHA following a single oral dose of 50 mg/kg body weight in female Swiss-Webster mice were investigated. Animals were sacrificed at time intervals up to 168 h after dosing. Levels of 3H were determined by liquid scintillation counting in the following tissues: brain, blood, serum, fat, heart, kidney, liver, lung, skeletal muscle and spleen. In most tissues the decline of BHA (log) was nonlinear with respect to time; a biphasic, post-absorptive aspect was observed. The highest 3H activity was noted in kidney and liver 15 min after dosing. The lowest activity was in fat. In addition, a peak 3H activity was recorded at 3 and 10 h after dosing for the blood and brain, respectively. Distribution of the 3H-BHA in mouse organs is similar to that in rat.

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The metabolism of butylated hydroxyanisole in the rabbit

Cited by 43 publications

References 11 publications

Distribution, metabolism, and excretion of musk xylene in rats

Distribution, metabolism, and excretion of musk xylene in rats

The Effect of the Level of Dietary Fat on the Toxicity of Phenolic Antioxidants

Tissue distribution and pharmacokinetics of3H-butylated hydroxyanisole in female mice

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