Tributylethylammonium ethyl sulphate

Endpoint summary

Link to relevant study record(s)

Reference

Endpoint:

basic toxicokinetics, other

Remarks:

Theoretical assessment taking all currently available relevant information into account.

Type of information:

other: expert statement

Adequacy of study:

key study

Study period:

2018

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Theoretical assessment taking all currrently 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.

Qualifier:

according to guideline

Guideline:

other: Guidance for the implementation of REACH. Guidance on information requirements and chemical safety assessment. Chapter R.7c: Endpoint specific guidance. European Chemical Agency

Version / remarks:

June 2017

GLP compliance:

no

Type:

absorption

Results:

For risk assessment purposes, 50% is used for oral and dermal and 100% for inhalation absorption

Conclusions:

A toxicokinetic assessment was performed based on the available data of the substance. Based on the physical/chemical properties of the substance, absorption factors for this substance are derived to be 50% (oral), 100% (inhalation) and 50% (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 the substance. Based on the physical/chemical properties of the substance, absorption factors for this substance are derived to be 50% (oral), 100% (inhalation) and 50% (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 (%):

50

Absorption rate - dermal (%):

50

Absorption rate - inhalation (%):

100

Additional information

A toxicant can enter the body via the gastrointestinal tract, the lungs and the skin. In general, a compound needs to be dissolved before it can be taken up from the gastrointestinal tract after oral administration.¹ Tributylethylammonium ethylsulfate (TBEAES) is highly water soluble (>1 x 10³g/L) and will therefore readily dissolve into the gastrointestinal fluids and make contact with the mucosal surface. Also, the molecular weight of TBEAES (340) and the low Log P (0.0 and -1.7) are favorable for absorption. However, TBEAES is a salt and expected to dissociate into ions in aqueous solution. As it is generally assumed that ionized substances do not readily diffuse across biological membranes, absorption is considered to be limited.

Taken together, the water solubility, molecular weight and Log P of TBEAES favor absorption. On the other hand, absorption is expected to be limited because TBEAES can form ions in solution. For risk assessment purposes oral absorption of TBEAES is set at 50%.²

 

For inhaled substances the processes of deposition of the substance on the surface of the respiratory tract and the actual absorption have to be differentiated. The vapour pressure of TBEAES was found to be low (8.3 x 10^-4Pa at 25°C), which indicates that the substance is not available for inhalation as a vapour. As TBEAES is marketed in aqueous solution formation of aerosols needs to be considered, which may be inhaled and enter the respiratory tract. If TBEAES reaches the tracheobronchial region, it is likely to diffuse/dissolve into the mucus lining of the respiratory tract due to its high water solubility and subsequently get absorbed due to its neutral log P.

Based on the above data, for risk assessment purposes the inhalation absorption of TBEAES is set at 100%.²

 

Exposure to TBEAES will be considered in aqueous solution. According to the criteria given in the REACH Guidance², a default value of 100% dermal absorption should be used unless MW >500 and log Pow <-1 or >4, in which case a value of 10% skin absorption should be chosen.  The MW (340) and log P (≤0.0) of TBEAES indicate that the criteria for 10% absorption are not met, and 100% dermal absorption should be considered. However, as it is generally accepted that dermal absorption will not be higher than oral absorption, the dermal absorption for TBEAES is set at 50% for risk assessment purposes.²

 

Once absorbed, wide distribution of the test substance throughout the body is expected based on its water solubility (>1 x 10³g/L), molecular weight (340) and partition coefficient (0.0 and -1.7). Absorbed TBEAES is most likely excreted via urine based on its good water solubility and being at least partly ionized at the pH of urine.³ Based on its partition coefficient and high water solubility, TBEAES is not expected to accumulate significantly in adipose tissue.

References

1       Martinez MN, Amidon GL. Mechanistic approach to understanding the factors affecting drug absorption: a review of fundamentals. J Clin Pharmacol 2002; 42: 620-43.

2       Guidance for the implementation of REACH. Guidance on information requirements and chemical safety assessment. Chapter R.7c: Endpoint specific guidance. European Chemical Agency, Version 3.0 November 2017.

3       Parkinson A. In: Casarett and Doull’s Toxicology, The basic science of poisons. Sixth edition. Ed. C.D. Klaassen. Chapter 6: Biotransformation of xenobiotics. McGraw-Hill, New York, 2001.