Registration Dossier
Registration Dossier
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EC number: 244-599-9 | CAS number: 21829-50-5
Endpoint summary
Administrative data
Link to relevant study record(s)
Description of key information
Key value for chemical safety assessment
Additional information
No studies on toxicokinetic behavior of [tris(2 -hydroxymethyl)ammonium] citrate are available.
Tris[(2-hydroxymethyl)ammonium] citrate is a neutral salt of monoethanolamine and citric acid. It is expected that upon uptake by the body, in aqueous media, the substance will exhibit behaviour typical for ionic salts and will dissociate into the respective monoethanolammonium cation and citrate anion. It is therefore expected that the toxicological profile of tris[(2-hydroxyethyl)ammonium] citrate will be governed by the toxicological profiles of free monoethanolamine and citric acid.
Citric acid is an important intermediate of the Krebs cycle (also known as citric acid cycle), and therefore occurs naturally as a metabolite in virtually all living organisms. It is also used as a natural food preservative and a food additive. The average daily intake (ADI) is not limited according to the evaluation ofJoint FAO/WHO Expert Committee on Food Additives (1973), which concluded that the substance is non-hazardous to men. Therefore the toxicological behavior of tris[(2-hydroxyethyl)ammonium] citrate is expected to be governed primarily by the toxicity of monoethanolamine.
The liver is the primary site for the metabolism of monoethanolamine and metabolites of monoethanolamine are found in urine of treated laboratory animals. Monoethanolamine is a normal constituent of the body (animal and human) and following condensation to phosphatidylethamolamine or transformation into phosphatidyl choline can be incorporated into cellular membranes. It can be converted into amino acids such as glycine and serine and incorporated into proteins. The molecule can be deaminated, with the amine group eliminated from the body as nitrogenous waste (urea or uric acid depending on the species) and the remaining carbon skeleton can be used as an energy source and oxidized fully to carbon dioxide. Monoethanolamine can be eliminated "unchanged" in the urine, with experiments in rats indicating that it is a dose-dependent phenomenom. This may be due to the saturation of metabolic pathways and suggests that excess levels in the body are not accumulated but can be directly eliminated via the kidneys. Ethanolamine is a normal constituent of human urine and in a limited numbers of subjects observed there was wide inter-individual variation of urinary levels (1).
Tris[(2 -hydroxyethyl)ammonium] citrate is very well soluble in water (334.43 g/L) and has an (estimated) log Kow of -8.6. According to Chapter R7.C of REACH guidance on information requirements and chemical safety assessment water-soluble substances will readily dissolve into the gastrointestinal fluids. Absorption of very hydrophilic substances by passive diffusion may however be limited by the rate at which the substance partitions out of the gastrointestinal fluid. For inhalation absorption, generally, water-soluble solids would readily diffuse/dissolve into the mucus lining the respiratory tract. Very hydrophilic substances might however be retained in the mucus and transported out of the respiratory tract.
In the abscence of quantitative data on the absorption of the substance, the default values according to Chapter R.8 of REACH Guidance on information requirements and chemical safety assessment will be taken forward to DNEL derivation. Regarding dermal absorption, if water solubility is above 10,000 mg/l and the log P value below 0 the substance may be too hydrophilic to cross the lipid rich environment of the stratum corneum. Dermal uptake for these substances is likely to be low.
In the abscence of quantitative data on the absorption of the substance, the default values according to Chapter R.8 of REACH Guidance on information requirements and chemical safety assessment will be taken forward to DNEL derivation.
References
1. Binks SP, Glass DC et al., Smillie MV. Criteria document for ethanolamine. CEC. Occupational exposure limits. Vol. 14240 (1992).
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