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

Abstract

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.

Toxicology and biochemistry of butylated hydroxyanisole and butylated hydroxytoluene

“…Other changes reported include diminished initial growth rate and loss of hair of rats fed BHT (11), increased electrolyte and aldosterene excretion in rabbits fed BHA or BHT (12), and an enlargement of the adrenals and increased ascorbic acid output of rats fed BHA or BHT (7,13). Other workers have failed to observe such changes in their studies (7).…”

“…The effects are virtually absent in both rodents and primates treated with 50 or less mg/kg body wt of BHA or BHT (8,14). Also long term chronic studies of BHA and BHT have shown little or no effects upon rats (11,(16)(17)(18), dogs (19,20), or monkeys (21).…”

Cell culture as a test system for toxicity

“…Extensive evidence supports the safety of BHT at appropriate dose levels (Gilbert & Goldberg, 1965;Ladomery, Ryan & Wright, 1967;Frawley, Kay & Calandra, 1965;Daniel, Gage & Jones, 1968;Clegg, 1965). A report by Johnson (1965) indicated that a dietary level of 0-5 % BHT (w/w) reduced the mean weight of offspring of mice, but disputes earlier work by Brown, Johnson & O'Halloran (1959) which suggested that BHT was teratogenic in mice.…”

Fatty Liver and Kidney Syndrome in Chicks II. Biochemical Role of Biotin

“…For example, Brown et al (1959) showed that hepatomegaly resulted from the feeding of antioxidant butylated hydroxytoluene (BHT) to rats. GllUnt et al (1965) confirmed these observations and showed that in addition the liver enzymes responsible for the detoxification of BHT and other drugs were hyperfunctional.…”