Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

ABSORPTION:


Oral absorption


Based on physicochemical properties and available data:


According to REACH guidance document R7. C, oral absorption is maximal for substances with molecular weights below 500; molecular weights above 1,000 do not favour absorption. Also, absorption by passive diffusion is higher at moderate log Kow vales (between -1 and 4) whereas uptake via micellar solubilisation may be important at log Kow values > 4. If signs of systemic toxicity are seen after oral administration (other than those indicative of discomfort or lack of palatability of the test substance), then absorption has occurred.


Based on these R7.C based indicative criteria, oral uptake of the test substance is assessed as moderate to high. The test substance is a mono constituent with MW of 302.4 g/mol, it is a liquid with a moderate water solubility (2.73 g/L) and low lipophilicity (with log Kow 0.467). The systemic availability of the substance via the oral route is demonstrated by a range of significant effects seen in acute oral and repeat dose studies, above dose levels of 300 mg/kg/d.


Conclusion: The oral uptake of the test substance is high, therefore the default value of 100% has been considered for risk assessment.


 


Dermal absorption


Based on physicochemical properties:


According to REACH guidance document R7.C (ECHA, 2017), dermal absorption is maximal for substances having a MW below 100 together with log Kow values ranging between 2 and 3 and water solubility in the range of 100-10,000 mg/L. Substances with MW above 500 are considered to be too large to penetrate skin. Further, dermal uptake is likely to be low for substances with log P values <-1, as they are not likely to be sufficiently lipophilic to cross the stratum corneum (SC). Similarly, substances with water solubility below 1 mg/L are also likely to have low dermal uptake, as the substances must be sufficiently soluble in water to partition from the SC into the epidermis.


The test substance is a liquid with a molecular weight of 302.4 g/mol, low to moderate water solubility (2.73 g/L at 20 oC) and a log Kow of 0.467 at 20 oC. this suggests the test substance is likely to have a low to moderate penetration potential through the skin. However, the test substance was found corrosive to skin when tested in an in vivo skin irritation/corrosivity study in rabbits. Therefore, dermal penetration may be enhanced due to damage to the skin.


Conclusion: Overall, based on all the physico-chemical information, the test substance can be expected to have a low to moderate absorption potential through the dermal route which may be enhanced due to the corrosive nature of the test substance. Therefore, a default value of 100% (in line with the ECHA Guidance Chapter R.8) has been considered for the risk assessment.


 


Inhalation absorption


Based on physicochemical properties:


According to REACH guidance document R7.C (ECHA, 2017), the vapour pressure indicates if the a substance is available for inhalation as a vapour and substances with low volatility have a vapour pressure of less than 0.5 kPa or a boiling point above 150 °C. The test substance has a vapour pressure of 1.0 x 10-2 Pa at 25 °C and will not be available as vapours for inhalation under ambient conditions. Should there be inhalation exposure during normal handling and use conditions, only coarse droplets would be potentially available for exposure, resulting in a very low respiratory fraction. Of the inhalable fraction, due to the moderate water solubility, the test substance could be retained in the mucus which would be transported to the pharynx and swallowed via the ciliary-mucosal escalator. The absorption potential of this fraction of the test substance can be considered to be similar to the oral route.  


Conclusion: Based on the above information, if exposure occurs, the test substance can be expected to have low absorption through the inhalation route. However, given systemic toxicity is observed via the oral route, a conservative approach has been used for risk assessment and a default value of 100% (in line with the ECHA Guidance Chapter R.8) is used.


Metabolism


Currently no investigation regarding metabolism of test substance is available.


DISTRIBUTION     


Per REACH guidance document R7.C (ECHA, 2017), the smaller the molecule, the wider the distribution. Small water-soluble molecules and ions will diffuse through aqueous channels and pores, although the rate of diffusion for very hydrophilic molecules will be limited. Further, if the molecule is lipophilic (log P >0), it is likely to distribute into cells and the intracellular concentration may be higher than extracellular concentration particularly in fatty tissues. 


Given the molecular weight of the substance and moderate water solubility, as well as systemic toxicity seen on repeat dose studies, the test substance is assumed to be distributed throughout the body and could be distributed to highly perfused organs/tissues. However, no specific target organ effects were noted on acute or repeat dose studies.


The low log Kow (0.467) combined with the observation of very low levels of bioaccumulation demonstrated in fish exposed via the dietary route, suggests the potential for bioaccumulation is low.


Conclusion: Based on all the available weight of evidence information, the test substance is likely to be distributed if absorbed, but with a low bioaccumulation potential.  


EXCRETION:     


Based on physicochemical properties:   


According to REACH guidance document R7.C (ECHA, 2017), the characteristics favourable for urinary excretion are low molecular weight (below 300 in the rat), good water solubility, and ionization of the molecule at the pH of urine (4.5 to 8). 


The test substance has a molecular weight of just above 300 and may therefore be excreted via urine. Further, it has been found in the rat that substances with molecular weights around 300 do not tend to be excreted into the bile. There are species differences, and the exact nature of the substance also plays a role. Without further information on the metabolism of the test substance it must be assumed that both excretion via urine and faeces is possible.


Conclusion: Based on all the available weight of evidence information, the test substance is expected to be excreted via urine and faeces.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
100
Absorption rate - dermal (%):
100
Absorption rate - inhalation (%):
100

Additional information

Based on the available weight of evidence information, the test substance is expected to have a moderate absorption potential via the oral route as well as through the inhalation route; absorption potential through dermal route is not relevant given the corrosive properties of the substance.