Salicylaldehyde

Endpoint summary

Description of key information

After administration of a single oral dose of 400 mg/kg bw of 2-hydroxybenzaldehyde to a fasted rabbit, 75% of the dose was excreted as ether-soluble acids in urine within 24 hrs, indicating that this substance was well absorbed via gastrointestinal tract. Urine analysis revealed that 27% and 3% of the dose was excreted as glucuronic acid and sulphate conjugates, respectively.

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Additional information

There is no specific requirement to generate toxicokinetic information in REACH. Therefore, the toxicokinetic profile of 2-hydroxybenzaldehyde (i.e. absorption, distribution, metabolism and elimination) was derived from the relevant available information from the SIDS dossier.

 

Physico chemical properties:

2-hydroxybenzaldehyde is a mono-constituent substance, having a low molecular weight of 122 g/mol. 2-hydroxybenzaldehyde is a colourless oily liquid at standard temperature and pressure with almond like odour.  Melting point and boiling point are -7 °C and 197 °C respectively. Vapour pressure is 75 Pa at 25 °C and partition coefficient between octanol and water (log K_ow) is 1.66 at pH 6.2 – 6.3. Water solubility is 4.9 g/L at 25 °C. As a dissociation constant (pK_a) in water is 8.28, 2-hydroxybenzaldehyde is partially dissociated in environmental water. However, un-dissociated form is dominant between pH 6 and pH 8.

 

Absorption: 

After administration of a single oral dose of 400 mg/kg bw of 2-hydroxybenzaldehyde to a fasted rabbit, 75% of the dose was excreted as ether-soluble acids in urine collected over 24 hrs, indicating that this substance was well absorbed via gastrointestinal tract [Bray, H.G. et al., 1952, reliability=2]. An in situ perfusion experiment also demonstrates that 2-hydroxybenzaldehyde could be well absorbed from rat small intestine [Nogami, H. et al., 1968, reliability=2].

No reliable studies are available regarding a dermal absorption of 2-hydroxybenzenaldehyde. However, systemic symptom (tremor) was observed in a skin irritation study using guinea pig although the quality of this data is not robust. Therefore, percutaneous absorption of this substance was suggested [Eastman Kodak Co., 1991, reliability=4]. 

 

Distribution: 

Systemic distribution of 2-hydroxybenzenaldehyde can be predicted from its physical chemical characteristics. Considering that the substance is lipophilic (log Pow >1) and slightly water soluble, it is suggested that, upon systemic absorption, 2-hydroxybenzenaldehydemay be transported through the circulatory system in association with a carrier molecule such as a lipoprotein or other macromolecule. Afterwards, based on its lipophilic character, the substance will readily cross cellular barriers or will be distributed into fatty tissues with a low potential to accumulate. 

 

Metabolism and excretion: 

In the above-mentioned study using a fasted rabbit, urine analysis revealed that 27% and 3% of the dose was excreted as glucuronic acid and sulphate conjugates, respectively [Bray, H.G. et al., 1952]. Although there is no other reliable data regarding the metabolism of 2-hydroxybenzaldehyde, the secondary literature reported that when fed to rabbits, phenolic aldehydes cause an increased excretion of glucuronides usually of the ether type, and ethereal sulphates, and, besides being oxidized to the corresponding acids, are also excreted as conjugated aldehydes [Williams, R.T., 1959, reliability=4]. The glucuronides have been detected in the urine of rabbits receiving 2-hydroxybenzaldehyde, and some of the free aldehyde is also excreted by rabbits. On the other hand, it was reported that the main metabolite of 2-hydroxybenzaldehyde in the dog, cat and rabbit is 2-hydroxybenzoic acid in this secondary literature [Williams, R.T., 1959, reliability=4].

 

References: 

From SIDS Initial Assessment Report For SIAM 32. 2-Hydroxybenzaldehyde. Paris, France, 18–22 April, 2011:

- Nogami, H., Hanano, M and Yamada, H (1968) Studies on absorption and excretion of drugs. IX, Relation between chemical structure and absorption rate. 1. Effects of the number and position of OH-groups on the intestinal absorption rate of benzoyl derivatives. Chem. pharm. Bull., Tokyo 16.299

- Eastman Kodak Co., 1991 OTS0533438, Doc#: 86-920000075

- Bray, H.G., Brenda, Humphris, G., Thorpe, W.V., White. K. and Wood, P.B. (1952) Kinetic studies of the metabolism of foreign organic compounds. The formatin of phenols from certain precursors. Biochem. J., 52, 412-415.

- Bray, H.G., Thorpe, W.V. and White, K. (1952) Kinetic studies of the metabolism of foreign organic compounds. A mathematical model expressing the metabolic fate of phenols, benzoic acids and their precursors. Biochem. J., 52, 423-430.

- Williams, R.T. (1959) Detoxication Mechanisums. The Metabolism and Detoxication of Drugs, Toxic Substances and Other Organic Compounds. 2nd Ed. p. 333, Chapman & Hall Ltd. London.