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EC number: 205-617-0 | CAS number: 144-15-0
In order to cross the skin, a compound must first penetrate into the stratum corneum and may subsequently reach the epidermis, the dermis and the vascular network. The stratum corneum provides its greatest barrier function against hydrophilic compounds, whereas the viable epidermis is most resistant to penetration by highly lipophilic compounds. Substances with a molecular weight (MG) below 100 are favourable for penetration of the skin and substances with a MG > 500 are normally not able to penetrate. The substance must be sufficiently soluble in water to partition from the stratum corneum into the epidermis. Therefore if the water solubility is below 1 mg/L, dermal uptake is likely to be low. Additionally LogPow values between 1 and 4 favour dermal absorption (values between 2 and 3 are optimal). Above 4, the rate of penetration may be limited by the rate of transfer between the stratum corneum and the epidermis, but uptake into the stratum corneum will be high. Above 6, the rate of transfer between the stratum corneum and the epidermis will be slow and will limit absorption across the skin. Uptake into the stratum corneum itself may be slow. Moreover vapours of substances with vapour pressures below 100 Pa are likely to be well absorbed and the amount absorbed dermally may be more than 10% of the amount that would be absorbed by inhalation. If the substance is a skin irritant or corrosive, damage to the skin surface may enhance penetration. During the whole absorption process into the skin, the compound may be subject to biotransformation.
In case of tris(2-ethylhexyl) 2-(acetyloxy)propane-1,2,3-tricarboxylate, the molecular weight is above 500, which indicates practically no potential to penetrate the skin. The very low water solubility will prevent significant uptake via the skin. The LogPow value for this substances is not optimal, its LogPow (5.7) does not favour dermal absorption. The systemic toxicity via the skin is assumed to be low and this has been proven with the results of the acute dermal toxicity study, which showed no mortality after dermal application of 2000 mg/kg bw in rats (tris(2-ethylhexyl) 2-(acetyloxy)propane-1,2,3-tricarboxylate).
In order to assess the toxicological behaviour of tris(2-ethylhexyl) 2-(acetyloxy)propane-1,2,3-tricarboxylate, the available experimental and predicted physico-chemical data have been evaluated. The unchanged substance is expected to be poorly absorbed after oral exposure (based on molecular weight, water solubility and LogPow value and experimentally derived data). This prediction for tris(2-ethylhexyl) 2-(acetyloxy)propane-1,2,3-tricarboxylate can not be reconsidered based on the acute toxicity data available for this substance, as the results do not clearly indicate that the rapid absorption noted is based on absorption of the unchanged compound. The absorption of any metabolite of the substances of interest is, however, fast and complete. Concerning the absorption after exposure via inhalation, as the chemical has a low vapour pressure, it is clear, that the substance is poorly available after inhalation. Tris(2-ethylhexyl) 2-(acetyloxy)propane-1,2,3-tricarboxylate is expected to be also poorly absorbed following dermal exposure into the stratum corneum and to a certain extent into the epidermis, due to its molecular weight of 570.8 g/mol and its LogPow of 5.7. In addition, the systemic toxicity via the skin is assumed to be low and this has been proven with the results of the acute dermal toxicity study with tris(2-ethylhexyl) 2-(acetyloxy)propane-1,2,3-tricarboxylate, which showed no mortality after dermal application of 2000 mg/kg bw in rats. Concerning the distribution in the body, tris(2-ethylhexyl) 2-(acetyloxy)propane-1,2,3-tricarboxylate is expected to be available in the circulatory system and to be distributed into the cells, since it is a lipophilic substance. The experimentally determined or calculated LogPow values, the water solubility and predicted behaviour concerning absorption show that the substance might have a potential for accumulation, but this is unlikely because of the extensive metabolism predicted and the limited absorption of unchanged tris(2-ethylhexyl) 2-(acetyloxy)propane-1,2,3-tricarboxylate. The substance is expected to be extensively metabolised by esterases and cytochrome P450 enzymes and break-down in the beta-oxidation or citric acid cycle or in cases subsequent glucuronidation. The substance is assumed to be excreted (if not metabolised completely in beta-oxidation and citric cycle) as metabolites (i.e. conjugates with glucuronic acid) via urine and to a lower extent via bile.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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