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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
Absorption rate - dermal (%):
Absorption rate - inhalation (%):

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 light yellowish liquid with a molecular weight of 206.28 g/mol and a moderate water solubility of 663 mg/L at 20 °C. The substance has a low vapour pressure of 10 Pa at 20 °C and the log Pow is 2.94 to 3.09 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 206.28 g/mol, favouring oral absorption of the compound. This is supported by the determined log Pow values of 2.94 to 3.09, being advantageous for oral absorption. Moreover, water-soluble substances will readily dissolve in the gastrointestinal fluids which favour oral absorption. One other mechanism, by which small water-soluble molecules (molecular weight up to around 200) can be absorbed in the GI tract include the passage through aqueous pores or carriage of such molecules across membranes with the bulk passage of water (Renwick, 1994). 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 (1979) signs of systemic toxicity were observed. In the 1.0 and 1.26 mL/kg bw dose groups 3 and 4 females died, respectively. In the 1.59 mL/kg bw group 4 males and 5 females were found dead within 4 days. Clinical signs were observed at all applied doses starting at 0.794 mL/kg bw and increased in severity up to 1.59 mL/kg bw. Coordination disorder, attitude and position anomaly, reduced or lack of the righting-reflex, grip reduction, hyperaemia, piloerection, decreased respiratory frequency and ptosis were detected 10 min after application and persisted partly longer than 24 hours. Reddening of the intestinal mucosa and the stomach lining was found in the moribund animals. Using Probit analysis, the LD50 for male and female rats was calculated to be 1.24 mL/kg bw (equivalent to 1265 mg/kg bw).

In a conducted 2-week repeated oral dose range-finding study, two males and five females were found moribund or dead at 600 mg/kg bw/day on Day 2. In the main study, a combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (2015) temporary loss of locomotor activity was observed in females at 300 mg/kg bw/day in the main and recovery group. Moreover, in the main group, increases in the absolute (+36%) and relative (+25%) organ weights of the liver were noted in males at 300 mg/kg bw/day. Relative increase in liver weight (+25%) was also observed in females at 300 mg/kg bw/day. Hepatocellular hypertrophy was observed in males at 100 mg/kg bw/day and in both sexes at 300 mg/kg bw/day in the main group, which was considered to be an adaptive response. Based on these results, the NOAEL for the test substance for systemic toxicity was considered to be 100 mg/kg bw/day for males and females due to the liver weight increases.

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 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 the molecular weight level of the test substance dermal uptake can be seen to be moderate. The log Pow value of the test substance is optimal for dermal absorption. For dermal uptake sufficient water solubility is needed for the partitioning from the stratum corneum into the epidermis. Therefore, if the water solubility is between 100 and 10000 mg/L the dermal absorption is anticipated to be moderate to high (ECHA, 2014).

The dermal permeability constant Kp of the substance was estimated to be 0.0098 – 0.0123 cm/h using DermwinTM(v.2.01) and taking into account the molecular weight of 206.29 g/mol and the log Pow of 2.94 and 3.09 for the two isomers, respectively. Thus taking also into account the water solubility of 663 mg/L, the absorption of the test substance is anticipated to be moderate to high. Data from an acute dermal toxicity limit test revealed piloerection 1 h after application in all male and 1 and 3 h after application in all female rats (1999). No mortality occurred and thus the dermal LD50 value was greater than 2000 mg/kg bw. Against the background of the demonstrated toxic potency after oral exposure, the dermal toxicity seems to be of no magnitude, presumably due to a lower dermal uptake in contrast to oral absorption.



Moderate log Pow 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 10 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 2.94 to 3.09) 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 (v3.4, OECD, 2016). 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. 17 hepatic and 4 dermal metabolites were predicted for the test substance, respectively. Primarily, hydroxylation of the substance occurs in the liver. In general, the hydroxyl groups make the substances more water-soluble and susceptible to metabolism by phase II-enzymes. Up to 65 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 (1999, 2015, 2015).



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, HelsinkiLiterature

Renwick,A.G. (1994) Toxicokinetics - pharmacokinetics in toxicology. In Hayes,A.W. (ed.) Principles and Methods of Toxicology. Raven Press, New York, p 103 as cited in ECHA 2014