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Description of key information

Methyl benzoate is hydrolysed by enzymes in vivo when entering the body through the gastrointestinal tract, the skin and the lungs. Enzyme mediated hydrolysis is ongoing in blood and other body fluids and in most tissues of the body after uptake into the body. Hydrolysis of methyl benzoate leads to the formation of benzoic acid and methanol. Benzoic acid and its salt sodium benzoate are rapidly metabolised in vivo and excreted via urine within 24 hours. Benzoic acid is readily conjugated with glycine, primarily in the liver, and excreted as hippuric acid. When glycine is depleted, free benzoic acid may sequester acetyl coenzyme A or be excreted unchanged, or as the glucuronic acid conjugate.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

Methyl benzoate is likely to be rapidly transformed into benzoic acid and methanol via enzymatic clevage by non-specific esterases in the gastrointestinal tract and when absorbed through the skin. This enzyme mediated hydrolysis occurs also in the blood, other body fluids and most body tissues. Benzoic acid has a pKa of 4.2 (Harris 2010) and therefore it is available in the dissociated form in the blood (blood pH 7.4). Also sodium benzoate is dissociated to benzoate in the body and therefore considered as additional read-across substance.

Oral absorption and metabolism

Methyl benzoate is hydrolysed to yield benzyl alcohol that is subsequently oxidized to benzoic acid as a stable metabolite or end product. Methyl benzoate is rapidly absorbed through the gastrointestinal tract (FFHPVC, 2002). The intestinal absorption of methyl benzoate is relatively high (k = 1.43) compared to the other methyl benzoate derivatives containing OH groups in the aromatic ring: Methyl salicylate, k = 1.42; Methyl m-hydroxybenzoate, k = 0.91; Methyl p-hydroxybenzoate; k = 1.03 (Nogami et al, 1968). Methyl benzoate is metabolised primarily in the liver, and excreted in the urine either unchanged or as conjugates of benzoic acid derivatives. At high doses, conjugation pathways (e.g. glycine) may be saturated and free benzoic acid may be excreted unchanged (FFHPVC, 2002).

Dermal absorption and metabolism

A fraction of about 40% of the applied topical dose of the read-across substance benzoic acid is absorbed through human skin and excreted via urine over a period of five days (Feldmann and Maibach 1970). Methyl benzoate is absorbed more efficiently than benzoic acid in in vitro tests with excised guinea pig skin, or is metabolised under experimental conditions in vitro (porcine skin). Meanwhile, the skin permeability log (kp) was estimated with an empirical approach using refined Potts and Guy models in USEPA Supplemental Guidance for Dermal Risk Assessment and was -2.16 cm/h (Xia et al, 2007).

Distribution

Methyl benzoate is anticipated to be hydrolysed during passage through the gastrointestinal walls, the skin and in lung tissues, in blood and other body fluids due to the activity of unspecific esterases. Enzyme mediated hydrolysis yields benzoic acid, which is expected to be distributed within the organisms. Because of the high rate of excretion, accumulation of benzoic acid in organs and tissues is not to be expected.

Metabolism

Benzoic acid is metabolised by conjugation with glycine or glucuronic acid. The main metabolite of this conjugation reaction is hippuric acid. When glycine is depleted, free benzoic acid may sequester acetyl coenzyme A or be excreted unchanged, or as the glucuronic acid conjugate. The major site of the conjugation of benzoic acid is the liver followed by the kidneys.

Excretion

Conjugates of benzoic acid are rapidly excreted within 24 hours via urine after oral, intraperitoneal and subcutaneous administration. The fecal excretion is a minor route of excretion.

References:

FFHPVC: The Flavor and Fragrance High Production Volume Consortia. The Aromatic Consortium. Test Plan for Benzyl Derivatives. 3-Jan-2002.

Feldmann RJ, Maibach HI. Absorption of some organic compounds through the skin in man. The Journal of investigative Dermatology 54, 5, 1970: 399-404.

Harris D. Quantitative Chemical Analysis (8 ed). New York: Freeman WH and Company 2010. pp. AP12. ISBN 9781429254366.

Xia X-R, Baynes RE, Monteiro-Riviere NA, Riviere JE. An experimentally based approach for predicting skin permeability of chemicals and drugs using a membrane-coated fiber array. Toxicology and Applied Pharmacology 221, 2007: 320-328.