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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

basic toxicokinetics
Type of information:
other: expert statement
Adequacy of study:
key study
Study period:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Theoretical assessment taking all currently available relevant information into account, based on the REACH Guidance: Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.7c Endpoint specific guidance. Since this is a theoretical assessment, the Klimisch value cannot be 1.
GLP compliance:
For risk assessment purposes, 100% is used for oral, dermal and inhalation absorption
A toxicokinetic assessment was performed based on the available data of 1,4-H6XDI. Based on the physical/chemical properties of 1,4-H6XDI, absorption factors are derived to be 100% (oral, inhalation and dermal) for risk assessment purposes. The bioaccumulation potential is expected to be low.

Description of key information

A toxicokinetic assessment was performed based on the available data of 1,4-H6XDI. Based on the physical/chemical properties of 1,4-H6XDI, absorption factors are derived to be 100% (oral, inhalation and dermal) for risk assessment purposes. The bioaccumulation potential is expected to be low.

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential
Absorption rate - oral (%):
Absorption rate - dermal (%):
Absorption rate - inhalation (%):

Additional information

After exposure, a substance can enter the body via the gastrointestinal tract, the lungs and the skin. Since different parameters are relevant depending on the route of exposure, the three routes will be addressed individually.

After oral administration, in general, a compound needs to be dissolved before it can be taken up from the gastrointestinal tract. In a hydrolysis study, 1,4-H6XDI was shown to rapidly disappear when dissolved in an aqueous solution. The speed at which this happens appears to be dependent on the pH, as at pH 4 the test item could only be detected at very low concentrations within the first 30 minutes, but was completely absent at later time points, while at pH 7 and pH 9 a gradual decrease was measured. At pH 7, the concentration of 1,4-H6XDI decreased to 25% of the start concentration after 3 hours, and became undetectable after 20 hours (no measurements in between), at pH 9 the concentration decreased below 10% after approximately 2,5 hours. These results indicate rapid hydrolysis. Since no stable degradation product was found, it is concluded that 1,4-H6XDI reacts with itself and/or hydrolysis/degradation products in all aquatic media, forming a complex mixture of numerous, high molecular weight products. As this process seems to take place more rapidly under acidic circumstance, it is highly likely that a similar process will take place in the stomach, where the pH is low. It is furthermore noted that this process is a highly random process, therefore it is not possible to predict which end products will be present after uptake. Furthermore, due to its reactivity after hydrolysis it cannot be excluded that the substance will react with other protein moieties present in the stomach. Since higher molecular complexes are formed, and it is known that larger sizes hamper uptake, the absorption of 1,4-H6XDI can be seen as a worst case and therefore the assessment will be performed on this molecule. 1,4-H6XDI has a limited size (molecular weight 194.23 g/mol) with a limited water solubility (calculated water solubility of 21.09 mg/L). The first parameter would indicate that the substance may pass through aqueous pores or be carried through the epithelial barrier by the bulk passage of water, albeit in a limited amount (low water solubility). The substance has a moderate partition coefficient (calculated log Pow = 3.92), which will also favour uptake via passive diffusion through lipid membranes. Therefore, for risk assessment purposes oral absorption of 1,4-H6XDI is set at 100%. The oral toxicity data does not provide reason to deviate from this conclusion.

1,4-H6XDI has a low vapour pressure (0.25 kPa at 100°C) and a boiling point above 150°C (255°C), which indicates that the substance is not very volatile and exposure to the substance as a vapour is unlikely. Since 1,4-H6XDI is a liquid, it is possible that aerosols are formed which can enter the lungs. The deposition pattern in the lung can be determined based on its distribution, although shape and electrostatic properties can influence this as well. Since aerosols are expected to be very small, they may reach the thoracic region and the alveolar region of the respiratory tract. Overall it is expected that the exposure via inhalation will be very limited. However, if the substance reaches the lung regions, 1,4-H6XDI is likely to react in the mucus lining of the respiratory tract to higher molecular forms (as described above). It is likely that due to its irritant properties the integrity of the lung epithelium is affected, which will lead to absorption of the substance. Based on this scenario, for risk assessment purposes the respiratory absorption of 1,4-H6XDI is set at 100%. The inhalation toxicity data does not provide reason to deviate from this conclusion. Dermal uptake of 1,4-H6XDI in an aqueous solution is facilitated by its liquid form. The dermal absorption is derived based on (calculated) physico-chemical properties of 1,4-H6XDI.

For this assessment any reactions the substance might undergo with itself, with breakdown products of itself, or with protein moieties of the skin, when exposed to air and surface moisture of the skin, were not taking into account. The main reason is that detailed information on the actual processes are missing. Furthermore, as described above, 1,4-H6XDI can be regarded as worst case for uptake.

For dermal absorption, the first layer of the skin, the stratum corneum, is a barrier for hydrophilic compounds. Based on its moderate log Pow (calculated log Pow = 3.92), crossing the first layer of the skin, the stratum corneum, is expected to take place. In order to partition from the stratum corneum into the epidermis, the substance must be sufficiently soluble in water. Since the calculated water solubility is low (21.09 mg/L), absorption is anticipated to be low to moderate. According to the guidance on dermal absorption, a default value of 100% skin absorption is generally used unless molecular mass is above 500 and log Powis outside the range [-1, 4]. Since the substance has a molecular weight of 194.23 and a calculated log Pow just below 4, it does not meet either criteria. In addition, the substance is corrosive to the skin, and is therefore expected to interfere with the integrity of the epidermal layer. Once the barrier function of the skin is compromised, dermal penetration is enhanced. Taking all aspects in consideration, the dermal adsorption for risk assessment purposes is set at 100%.

After oral absorption, 1,4-H6XDI might be metabolized in the gastro-intestinal tract. As the molecular weight of 1,4-H6XDI is relatively low, excretion of 1,4-H6XDI and its metabolites will occur via the bile (high molecular weight) or the urine (low molecular weight). Once absorbed, limited distribution of 1,4-H6XDI throughout the body is likely to take place based on its low water solubility and moderate molecular weight. Since hydrolysis and subsequent reactivity is anticipated, it can also be expected that high molecular weight molecules are formed, which are less likely to distribute systemically. Moreover, 1,4-H6XDI is considered to be highly reactive after hydrolysis, and also reactivity with protein moieties at site of contact are expected, which will further limit distribution. Overall, several scenarios are possible, which are likely to occur in parallel. Based on its moderate partition coefficient, 1,4-H6XDI is not expected to significantly accumulate in adipose tissue. Potential reaction products will have a high molecular size, which will also limit their accumulation in the organism. Overall, the bioaccumulation is expected to be low.