Glyoxylic acid

Endpoint summary

Additional information

Absorption

Oral absorption:

The systemic effects seen after oral administration demonstrate that Glyoxylic Acid 50% is absorbed from the GI tract.

Due to the pKa value of 3.1 Glyoxylic Acid 50% will be mostly non-ionised at the low pH of the stomach, whereas it will be mostly ionized at the pH value of the small intestine. Even though non-ionised substances are better absorbed than ionised substances, absorption after oral exposure will mostly occur in the small intestine and only to a minimal extent in the stomach because absorption area as well as vascularisation is much less in the stomach in comparison to the small intestine.

The low molecular weight (74.04 g/mol) and log Pow (-0.7) of Glyoxylic Acid 50% favour the absorption via passive diffusion, e.g. by passage through aqueous pores or carriage through the epithelial barrier with the bulk passage of water. Under normal physiological conditions, pH values below the pKa value of Glyoxylic Acid 50% can not be achieved in the intestine, thus, quantitative absorption in the intestine will not occur.

Dermal absorption:

Glyoxylic Acid 50% has a molecular weight less than 100 Dalton. Even though such a low molecular weight favours dermal uptake in general, passage through the lipid rich environment of the stratum corneum will be very restricted due Glyoxylic Acid 50%’s very high water solubility (fully miscable with water, calculated water solubility of 1000 g/l), the log Pow value of – 0.7 and the fact that the substance will be largely ionized at the skin’s physiological pH. Therefore, dermal uptake of Glyoxylic Acid 50% will be significantly lower than oral absorption. This is also supported by the available acute toxicity data, where clinical signs and mortality were seen in rats after oral administration but not after dermal administration of 2000 mg/kg bw.

Respiratory absorption:

Due to the moderate vapour pressure 1.4 kPa (boiling point of 111 °C) and the general potential of aqueous products to form aerosols inhalation exposure to Glyoxylic Acid 50% is feasible. Vapours of hydrophilic substances such as Glyoxylic Acid 50% are effectively removed from the air in the upper respiratory tract, thus restricting the absorption through the gas exchange region. The rate of systemic uptake may be limited by the rate at which the substance partitions out of the aqueous fluids (mucus) lining the respiratory tract and into the blood. Due to the low molecular weight, absorption through aqueous pores is possible. Alternatively the substance may be retained in the mucus, transported out of the deposition region with the mucus and subsequently swallowed. It can be concluded that systemic absorption after inhalation exposure is limited and not higher than absorption after oral exposure.

Distribution

Glyoxylic Acid is a metabolic intermediate of ethylene glycol. In a case of ethylene glycol poisoning Garibotto et al. (1988) reported a basal blood level for Glyoxylic Acid of 62.9 µmol/L (after accidental intake of 500 ml of a window cleaner containing 12.5 % ethylene glycol), a value greatly exceeding both the levels reported in normal subjects in plasma (1 ± 1.5 µmol/L) and those found in whole blood of healthy volunteers (3.1 ± 2 µmol/L). Additionally, the incomplete dialysance of Glyoxylic Acid suggests, that Glyoxylic Acid binds to plasma proteins (Garibotto et al., 1988). Due to its low log Pow value, Glyoxylic Acid 50% has no accumulation potential.

Metabolism

Glyoxylic Acid is metabolised via a number of intermediate metabolic pathways. The major metabolic route in terms of toxicological importance is the conversion to oxalic acid either by the liver peroxisome-specific glycolate (L-2-hydroxyacid) oxidase A, which has a broad substrate specificity that includes glyoxylate, or by lactate dehydrogenase (LDH) in the cytosol and interstitial tissue fluids (Watts, 1997). Physiologically important pathways which do not lead to toxicologically relevant metabolites are the formation of glycine by alanine:glyoxylate aminotransferase (AGAT) (Watts, 1997) and the oxidation via formic acid to carbon dioxide and water.

Excretion

Glyoxylic Acid 50% is mainly excreted renally as parent compound or oxalic acid.

Hockaday et al. (1964) found that the excretion of Glyoxylic Acid by normal adults ranged from 2.2 to 6 mg/d. This agrees with the findings of Zarembski et al. (1965) who found 1.4 to 4.7 mg/d of Glyoxylic Acid in 10 human urine samples. In urinary specimens from 27 infants (2-14 years) Aksu et al. (1974) determined Glyoxylic Acid excretions of 1.45 ± 1.69 mg/d. Hockaday et al. (1965) reported lower values (0.8 ± 0.2 mg/d) in 5-11 year old infants. In humans the urinary excretion of Glyoxylic Acid is increased in hyperoxaluric adult patients, from 2.18 ± 1.64 µmol/24 hrs to 30.10 ± 18.50 µmol/24 hrs (Watts, 1997).

In a study with rats Carbon-14 (C-14) Glyoxylic Acid (0.06 mmol) was administered by intraperitoneal injection together with sodium-benzoate (Weinhouse et al., 1951). Doses totaling 1 mmol of sodium-benzoate with the labelled acid as the sodium salt were administered. The rate of oxidation as indicated by the appearance of C-14 activity in carbon-dioxide (CO2) was studied at 0.5 hour intervals for 5 hours. Rates of oxalic acid and hippuric acid formation were measured in urine for 24 hours. Glyoxylic Acid was excreted to 16 % in respiratory CO2, 27.1 % as oxalic acid and 22 % as hippuric acid in the urine.

References (not created automatically during CSR creation)

Aksu A, Morrow G, Barness LA (1974). Urinary Excretion of Non-Nitrogenous Organic acids by healthy Infants and children. Clin. Chem. 20/5: 603-605.

Garibotto G, Paoletti, E, Acquarone N (1988). Glyoxylic Acid in Ethylene Glycol Poisoning. Nephron; 48: 248-249.

Hockaday TDR et al. (1964). Primary Hyperoxaluria. Medicine (Baltimore). 43: 315-45.

Hockaday TDR, Clayton JE, Smith LH Jr. (1965). The metabolic error in primary hyperoxaluria. Arch Dis Child. 40: 485-491.

Zarembski PM, Hodgkinson A (1965). The fluorimetric microdetermination of glyoxylic acid in blood, urine and bacterial extracts. Biochem J., 96 (1): 218–223.