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Up to 10 g of benzoate are excreted quantitatively (Barnes, 1959).

3-Hydroxy-isobutyrate

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No free benzoic acid was detected in the urine.

Aromatic esters can be expected to be hydrolysed by the catalytic activity of carboxylesterases or esterases (Heymann, 1980). B-Esterases, the most important of the group, are active in most mammalian tissue (Heymann, 1980; Anders, 1989) but predominate in hepatocytes (Heymann, 1980). Acetals hydrolyse uncatalysed in gastric juice and intestinal fluids to yield the corresponding aldehydes. , substituted benzyl esters and benzaldehyde acetals are hydrolysed to the corresponding alcohols, aldehydes, and carboxylic acids.

Flavouring agentBenzyl acetate is an organic compound with the molecular formula C9H10O2.

The elimination of benzyl acetate and metabolites was essentially complete by three days, as negligible residues were found in tissue, regardless of whether benzyl acetate was given pure or in corn oil.

Butyl-para-hydroxybenzoate (No. 870)

Benzyl alcohol was evaluated at the twenty-third meeting (Annex 1, reference 50).

Butyl--hydroxybenzoate was dissolved in soya bean oil at a concentration of 100 mg/0.5 ml and administered by oral intubation to rats for 13–15 weeks at concentrations calculated to result in a daily intake of 0, 0.25, or 50 mg/kg bw. Body weight, measured twice weekly, showed no significant difference from controls. Some animals were killed on a predetermined schedule for histological evaluation. There were no sporadic deaths and no significant histological differences from controls. The NOEL was 50 mg/kg bw per day (Ikeda & Yokoi, 1950).

Groups of 12 Wistar rats of each sex were fed a powdered mixture of butyl--hydroxybenzoate and dog chow providing a dose of 0, 2000, or 8000 mg/kg bw per day for 12 weeks. Body weight and food intake were measured every 2 weeks, and necropsy and histological examinations were performed at the end of the experiment. Animals found dead before the end of the study were necropsied and the appropriate tissues were fixed for histopathological evaluation. Although there were no effects at the low dose, all the males and many of the females at the high dose died within several weeks of the beginning of treatment. The body weights and motor activity of these animals were decreased, and they had a slower growth rate than controls. The NOEL was 2000 mg/kg bw per day (Matthews et al., 1956).

Butyl-para-hydroxybenzoate (No. 870)

Acute toxicity of benzyl acetate, benzyl alcohol, benzaldehyde, benzoic acid, benzoate salts, and benzyl benzoate Species Route LD50 Reference (mg/kg bw) Benzyl acetate Rat Oral 2490-3690 Jenner et al.( 1964); von Oettingen (1960) Rabbit Oral 640 von Oettingen (1960) Benzyl alcohol Mouse Intraperitoneal 650 (7 days) McCloskey et al.

Documented effects on the urea cycle, gluconeogenesis, fatty acid metabolism, carnitine status, and the tricarboxylic acid cycle were attributed to sequestering of coenzyme A by benzoate as a result of glycine depletion required for the formation of hippuric acid from benzoyl coenzyme A.

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  • para-Methoxybenzaldehyde (No. 878) and piperonal (No. 896)

    Benzaldehyde was evaluated at the eleventh meeting, when a monograph was prepared (Annex 1, references 14 and 15).

  • Methyl-ortho-methoxybenzoate (No. 880)

    Isobutyric acid

  • Butyl-para-hydroxybenzoate (No. 870)

    Benzyl acetate was readily hydrolysed in vitro by a pancreatin preparation (Grundschoser, 1977).

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2,4-Dihydroxybenzoic acid (No. 908)

Large oral doses of benzoic acid used therapeutically to alleviate the effects of inherited urea cycle disorders were studied with respect to their effect on intermediary metabolism.

(1971) Suspected benzoic acid poisoning in the cat.

(1954) Rat Intravenous (Na salt) 1714 ± 124 Spector (1956) Rat Oral (acid) 2000-2500 Ignat'ev (1965) Rabbit Oral (Na salt) 2000 Spector (1956) Rabbit Subcutaneous (Na salt) 2000 Spector (1956) Dog Oral (Na salt) 2000 Spector (1956) Benzyl acetate Groups of five B6C3F1 mice or Fischer 344 rats of each sex were administered single doses of benzyl acetate (purity, 96.0-101.3%) at doses of 250, 500, 1000, 2000, or 4000 mg/kg bw in corn oil by gavage and were observed for 15 days.

(1970) The fate of benzoic acid in various species.

Mice fed 3 g sodium benzoate daily for 10 days had a 10% reduction in creatine output, probably due to depletion of the glycine pool (Polonowski & Boy, 1941).

(1986) Studies on benzyl acetate.

A group of 10 male and 10 female weanling rats received a diet containing a mixture of eugenol (90 mg/kg bw), -methoxybenzaldehyde (7.3 mg/kg bw), and piperonal (16 mg/kg bw) at a concentration calculated to provide an average daily intake of 110 mg/kg bw for 90 days. Food intake and growth were measured each week. After 12 weeks on the test material, sugar, albumin, and haemoglobin concentrations were measured in the urine of three male and three female animals. No sugar was found; although the urine of male rats contained albumin, the authors considered the finding pathologically insignificant. All surviving animals were killed at 90 days and necropsied, and organs were weighed. Weekly measurements of body-weight gain, food intake, haematological and clinical chemical end-points, and gross and histological examinations showed no significant difference between test and control animals. The NOEL was 7.3 mg/kg bw per day for -methoxy-benzaldehyde (No. 878) and 16 mg/kg bw per day for piperonal (No. 896) (Trubeck Laboratories Inc., 1958).

(1987) Studies on benzyl acetate.

Groups of five male and five female 8-week-old rats were fed diets containing -methoxybenzaldehyde (No. 878) and piperonal (No. 896) at a concentration providing 500 mg/kg bw per day for 16 weeks, and groups of five male and five female 4-week-old rats were fed the same substances at 50 mg/kg bw per day for 28 weeks. One control group of 20 rats was used for each experiment. No gross pathological changes were seen in any group. The NOEL was 500 mg/kg bw per day for both -methoxybenzaldehyde and piperonal (Food & Drug Administration, 1954).

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