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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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 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. Widely distribution within the water compartment of the body after systemic absorption is because of lipophilicity of the test substance not expected. However, the distribution into cells particularly in fatty tissues is likely. Based on its log Pow the test substance is not considered to accumulate. The test substance might be metabolized after absorption. Excretion predominantly via the urine is expected.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

In accordance with Annex VIII, Column 1, Item 8.8 of Regulation (EC) 1907/2006 and with Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance (ECHA, 2014), 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 colourless to yellowish liquid with a molecular weight of 204.29 g/mol and a water solubility of 1.6 g/L at 20 °C. The substance has a low vapour pressure of 6 Pa at 20 °C and the log Pow is 2.43 to 2.9 at 22.8 °C for the two isomers of the substance, respectively.



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, 2014).




In general, low molecular weight (MW≤500) and moderate lipophilicity (log Pow values of -1 to +4) are favourable for membrane penetration and thus absorption. The molecular weight of the test substance is relatively low with 204.29, favouring oral absorption of the compound. This is supported by the determined log Pow values of 2.43 to 2.9, being advantageous for oral absorption. In addition the good water solubility of 1.6 g/L leading to a ready dissolving of the compound in the gastrointestinal fluids favours oral absorption.

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 conducted with the test substance in rats marked signs of systemic toxicity were observed at 200 and 2000 mg/kg bw (2001). Two animals treated with 2000 mg/kg bw died within 3 days after administration and one animal was sacrificed in extremis one day after dosing. Signs of systemic toxicity noted at this dose level were hunched posture, lethargy, decreased respiratory rate, gasping, laboured and noisy respiration, ataxia, ptosis, dehydration, increased lachrymation, hypothermia, body tremors, prostration, chromodacryorrhea, loss of righting reflex, pilo-erection and splayed gait. No mortality was observed at 200 mg/kg bw. Signs of systemic toxicity noted at this dose level were hunched posture, lethargy, ataxia, decreased respiratory rate, laboured respiration, increased salivation and splayed gait. Abnormalities noted at necropsy of animals that died or were killed in extremis during the study were haemorrhagic lungs, dark liver or patchy pallor of the liver, dark kidneys, haemorrhage and sloughing of the gastric mucosa, sloughing of the non-glandular region of the stomach and haemorrhagic small intestine. No abnormalities were noted at necropsy of animals that were killed at the end of the study. In this acute oral toxicity study in rats a LD50 value of 300 - 500 mg/kg bw was found. Additionally, a repeated-dose oral toxicity study in rats was conducted with the test substance (2013). In a dose range-finding study, animals were treated at concentrations of 50, 150 and 500 mg/kg bw/day for 14 days. At 500 mg/kg bw/day two females were found dead on Day 4 and one male and female were found dead on Day 5. The remaining animals at this dose level were sacrificed on Day 5 of the treatment period due to ethical reasons. No mortality was noted at 50 and 150 mg/kg bw/day. No test substance-related macroscopical findings were observed at necropsy in males and females at any dose level. In the main study, animals were treated with test substance at concentrations of 10, 40 and 200 mg/kg bw/day. No mortality was observed due to the treatment with the test substance within the study period. Significant reduced food consumption was observed at 200 mg/kg bw/day. Based on available data from the acute oral and repeated dose toxicity study, oral toxicity was observed 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 Log P value of the test substance is optimal for dermal absorption. Also for dermal uptake sufficient water solubility is needed for the partitioning from the stratum corneum into the epidermis.

The dermal permeability constant Kp of the substance was estimated to be 0.00668 cm/h using DermwinTM(v.2.01) and taking into account an estimated log Pow of 2.67 and the molecular weight of 204.29. Thus the absorption of the test substance is anticipated to be moderate to high.

Data from an acute dermal toxicity study revealed no effects of the test substance up to the limit dose of 2000 mg/kg bw (Sanders, 2001). Against the background of the demonstrated toxic potency after oral exposure, the dermal toxicity seems to be of low magnitude, presumably due to lower dermal uptake in contrast to oral absorption.


Moderate log P values (between -1 and 4) are favourable for absorption directly across the respiratory tract epithelium by passive diffusion. However, the test substance has a low vapour pressure of 6 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 the 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, 2014).

Since the test substance is lipophilic (log Pow 2.43 to 2.9) 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. Substances with log P values of 3 or less would be unlikely to accumulate in adipose tissues with the repeated intermittent exposure patterns normally encountered in the workplace but may accumulate if exposures are continuous. Once exposure to the substance stops, the substance will be gradually eliminated at a rate dependent on the half-life of the substance.



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 (v3.3, 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. 12 hepatic and 12 dermal metabolites 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 63 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 and HPRT test and micronucleus test in mammalian cells in vitro) were negative, with and without metabolic activation (2001, 2015, 2014).



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) and the water solubility of the molecule are properties favouring excretion via urine. Thus the test substance is expected to be excreted predominantly via the urine.



ECHA (2014): Guidance on information requirements and chemical safety assessment – Chapter 7c: Endpoint specific guidance. European Chemicals Agency, Helsinki