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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Link to relevant study record(s)

Description of key information

No studies regarding toxicokinetics, metabolism and distribution in the mammalian body of the test substance are available. The molecular weight, physicochemical properties incl. water solubility and octanol-water partition coefficient of the substance suggest that oral, inhalative and dermal absorption occur. Wide distribution within the water compartment of the body after systemic absorption is not expected due to the lipophilicity of the test substance. However, the distribution into cells, particularly in fatty tissues is likely. Based on its log Pow the test substance is considered to accumulate. The test substance might be metabolized after absorption.

Key value for chemical safety assessment

Bioaccumulation potential:
high bioaccumulation potential

Additional information

In accordance with Annex VIII, Column 1, Item 8.8 of Regulation (EC) No 1907/2006 and with Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance (ECHA, 2017), assessment of the toxicokinetic behaviour of the test substance was conducted to the extent that can be derived from the relevant available information on physicochemical and toxicological characteristics. There are no studies available evaluating the toxicokinetic properties of the substance.

 The test substance is a clear colorless liquid with a molecular weight of 226.40 g/mol and a low water solubility of 2.00 mg/L at 20°C. The substance has a low vapour pressure of 0.01 hPa at 20°C and the log Pow is 5.66 at 25°C.



The major routes by which the test substance can enter the body are via the lung, the gastrointestinal tract, and the skin. To be absorbed, the test substances must transverse across biological membranes either by active transport mechanisms or - as being the case for most compounds - by passive diffusion. The latter is dependent on compound properties such as molecular weight, lipophilicity, or water solubility (ECHA, 2017).



Generally the smaller the molecule the more easily it may be taken up. The molecular weight of the test substance is relatively low with 226.40 g/mol, favouring oral absorption of the compound. However, the absorption of highly lipophilic substances (log Pow > 4) may be limited by the inability to dissolve into gastrointestinal fluids and hence make contact with the mucosal surface. Micellar solubilisation by bile salts may enhance absorption, a mechanism which is especially of importance for highly lipophilic substances with log Pow >4 and low water solubility (Aungst and Shen, 1986).

Moreover, the observation of systemic toxicity following exposure by any route is an indication for substance absorption; however, this will not provide any quantitative information.

In an acute oral toxicity study, a total dose of 20 mL/kg bw (corresponding to 18000 mg/kg bw based on a density of 0.9 g/cm³) of the test substance was administered to 10 male and 10 female rats by gavage (Key, 1977). No mortality occurred during the observation period. All animals exhibited disturbances in coordination, diarrhea and piloerection beginning within 3 h after dosage and persisting for 24 h. Macroscopic post mortem examination did not reveal any abnormalities. In this acute oral toxicity study in rats the LD50 value was determined to be > 20 mL/kg bw (corresponding to > 18000 mg/kg bw based on a density of 0.9 g/cm³).

Additionally, a repeated-dose oral toxicity study combined with a reproduction/developmental toxicity screening Test (OECD 422) in rats was conducted with the test substance (Key, 2017). Animals were treated via gavage at dose levels of 60, 200 and 600 mg/kg bw/day. No test substance related mortality was observed. Mucous stool was mainly observed in males and females at 600 mg/kg bw/day. Increase in liver weights and hepatocellular hypertrophy based on an adaptive response was observed in animals of both sexes at 600 mg/kg bw/day. Total litter size of pups was significantly decreased at 600 mg/kg bw/day. Based on the results of this study, the systemic NOAEL was considered to be 600 mg/kg bw/day. The NOAEL for fertility and developmental toxicity were considered to be 200 and 600 mg/kg bw/day, respectively.

Based on the data available from the acute oral and repeated dose toxicity study, adverse effects were observed after oral exposure with the test substance and thus absorption of the test substance via the gastrointestinal tract has evidently occurred.


The dermal uptake of liquids and substances in solution is generally expected to be higher than that of dry particles. Molecular weights below 100 g/mol favour dermal uptake, while for those above 500 g/mol the molecule may be too large. Thus, for this molecular weight level of the test substance dermal uptake can be seen to be moderate. The substance must be sufficiently soluble in water to partition from the stratum corneum into the epidermis. Therefore, if the water solubility is between 1-100 mg/L, dermal uptake is considered to be low to moderate. For substances with log Pow 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.

The dermal permeability constant Kp of the substance was estimated to be 0.485 cm/h using DermwinTM (v.2.01) and taking into account a determined log Pow of 5.66 and the molecular weight of 226.4 g/mol. Thus the absorption of the test substance is anticipated to be moderate to low and assumed to be 50%.


Any highly lipophilic compound (logPow > 4) may be taken up by micellular solubilisation. However, the test substance has a low vapour pressure of 1 Pa at 20 °C. Therefore, under normal use and handling conditions, inhalation exposure and thus availability for respiratory absorption of the substance in the form of vapour can be considered negligible.


Distribution of a compound within the body depends on the physicochemical properties of the substance especially the molecular weight, the lipophilic character and the water solubility. In general, the smaller the molecule, the wider is its distribution. If the molecule is lipophilic, it is likely to distribute into cells and the intracellular concentration may be higher than extracellular concentration particularly in fatty tissues (ECHA, 2017).

Since the test substance is lipophilic (log Pow 5.66) the distribution into cells is likely and the intracellular concentration may be higher than extracellular concentration particularly in fatty tissues, if the substance is absorbed systemically. Lipophilic substances will tend to concentrate in adipose tissue and depending on the conditions of exposure may accumulate. If the interval between exposures is less than 4 times the whole body half-life of the substance then there is the potential for the substance to accumulate. It is generally the case that substances with high log P values have long biological half-lives. On this basis, daily exposure to a substance with a log P value of around 4 or higher could result in a buildup of that substance within the body. Once exposure to the substance stops, the substance will be gradually eliminated at a rate dependent on the half-life of the substance. If fat reserves are mobilized more rapidly than normal, e.g. if an individual or animal is under stress or during lactation, there is the potential for large quantities of the parent compound to be released into the blood (ECHA, 2017). Since no experimental data are available, a bioaccumulation potential is assumed.


No metabolism studies are available with the test substance itself. Prediction of compound metabolism based on physicochemical data is very difficult. Structure information gives some but no certain clue on reactions occurring in vivo. The potential metabolites following enzymatic metabolism were predicted using the QSAR OECD toolbox (v3.4, OECD, 2014). This QSAR tool predicts which metabolites may result from enzymatic activity in the liver and in the skin, and by intestinal bacteria in the gastrointestinal tract. 8 hepatic and 1 dermal metabolite were predicted for the test substance, respectively. Primarily, hydroxylation of the substance occurs in the liver and skin. In general, the hydroxyl groups make the substances more water-soluble and susceptible to metabolism by phase II-enzymes. Up to 66 metabolites were predicted to result from all kinds of microbiological metabolism for the test substance. Most of the metabolites were found to be a consequence of the degradation of the molecule. There was no evidence for differences in genotoxic potencies due to metabolic changes in in vitro genotoxicity tests. The studies performed on genotoxicity (Ames test, HPRT test and micronucleus test in mammalian cells in vitro) were negative, with and without metabolic activation (Key, 2006; Key, 2016; Key, 2016).


The major routes of excretion for substances from the systemic circulation are urine and/or faeces (via bile and directly from the GI mucosa). Only limited conclusions on excretion of a compound can be drawn based on physicochemical data. Due to metabolic changes, the finally excreted compound may have few or none of the physicochemical properties of the parent compound. In addition, conjugation of the substance may lead to very different molecular weights of the final product. The molecular weight (< 300 g/mol) of the molecule is a property favouring excretion via urine, while its low water solubility of 2.0 mg/mL is not. Thus, based on the available data no final conclusion on the excretion route is possible.



Aungst,B. and Shen,D.D. (1986) Gastrointestinal absorption of toxic agents. In Rozman,K.K. and Hanninen,O. (eds.) Gastrointestinal Toxicology. Elsevier, New York as cited in ECHA (2017), R.7c

ECHA (2017): Guidance on information requirements and chemical safety assessment – Chapter 7c: Endpoint specific guidance. European Chemicals Agency, Helsinki