Bis(2-ethylhexyl) carbonate

Endpoint summary

Description of key information

Experimental data are available for the percutaneous absorption of Bis(2-ethylhexyl) carbonate as well as for hydrolysis in gastric and intestinal fluids. 
Bis(2-ethylhexyl) carbonate is not expected to penetrate the human skin based on the available data. 
An in vitro hydrolysis study showed a hydrolysis of Bis(2-ethylhexyl) carbonate of about 65% within 4 hours in gastric-fluid simulant and a hydrolysis of about 15% within 4 hours in intestinal-fluid simulant. The branched-chain alcohol will be metabolised by omega- and omega-1-oxidation or conjugated with glucuronic acid and finally excreted via the urine.
No potential for bioaccumulation is to be expected.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

10

Additional information

The toxicokinetic assessment of Bis(2-ethylhexyl) carbonate is based on experimental data as well as on physicochemical properties. Experimental data are available for the percutaneous absorption of Bis(2-ethylhexyl) carbonate as well as for hydrolysis in gastric and intestinal fluids.

Absorption

Oral absorption

According to the “Guidance on information requirements and chemical safety assessment, Chapter R.7c: Endpoint specific guidance” (November 2012) “log P values between -1 and 4 are favourable for absorption. Nevertheless, a substance with such a log P value can be poorly soluble in lipids and hence not readily absorbed when its water solubility is very low.”

“The absorption of highly lipophilic substances (log P of 4 or above) may be limited by the inability of such substances to dissolve into GI fluids and hence make contact with the mucosal surface.”

The physicochemical properties of Bis(2-ethylhexyl) carbonate (log P = 4.1, poor water solubility of 0.03 mg/L) are not in a range suggestive of absorption from the gastro-intestinal tract subsequent to oral ingestion. However, the substance is hydrolysed in the gastrointestinal tract to 2-Ethylhexanol and Carbon dioxide. Thus, the physicochemical properties of the parent compound may no longer apply. For chemical safety assessment an oral absorption rate of 100% is assumed as a worst case value.

 

Dermal absorption

The percutaneous absorption of Bis(2-ethylhexyl) carbonate (99.9% a.i.) was assayed by using an in vitro method according to OECD Guideline 428, adopted 13. April. 2004. The penetration profile of the test item in human abdominal skin was analysed using anin vitroflow-through diffusion cell. A validated GC-MSD method was used to measure Bis(2-ethylhexyl) carbonate in cell culture medium (DMEM with 10% FCS). The results of the in-study validation data show that the used method is able to quantify the test item in cell culture medium with the respective precision and accuracy down to a concentration of 10.0 µg/mL, corresponding to a detection limit of 0.025%. No Bis(2-ethylhexyl) carbonate could be detected in the skin penetration samples up to a skin exposure time of 24h. Therefore, Bis(2-ethylhexyl) carbonate is not expected to penetrate the human skin.

For chemical safety assessment a dermal absorption rate of 10% is assumed as worst case value.

 

Inhalative absorption

Inhalation is not a relevant route of exposure to Bis(2-ethylhexyl) carbonate. Bis(2-ethylhexyl) carbonate is a liquid. Generation of inhalable vapour or aerosols is not to be expected. Vaporisation needs not to be considered due to the substance’s very low vapour pressure (1.0E-04 hPa at 20°C). Although the substance may be used in a spray application, the droplet size is > 50 µm and thus, the use will not result in inhalable fractions.

 

Distribution

As the primary metabolite 2 -Ethylhexanol is a small molecule, a wide distribution can be expected in general. No information on potential target organs is available.

 

Metabolism and elimination

The organic branched chain carbonate Bis(2-ethylhexyl)carbonate is expected to be acid labile and thus will break down to its carbonate and alcohol moieties at contact with the acidic gastric juice resulting in carbon dioxide and 2-Ethylhexanol.

The results of an in vitro hydrolysis study showed a hydrolysis of Bis(2-ethylhexyl) carbonate of about 65% within 4 hours in gastric-fluid simulant and a hydrolysis of about 15% within 4 hours in intestinal-fluid simulant. Enzymes capable of hydrolysing Bis(2-ethylhexyl) carbonate are present in the gastrointestinal tract, and thus Bis(2-ethylhexyl) carbonate will start to be metabolised prior to absorption.

2-Ethylhexanol as a branched-chain alcohol with a bulky side chain (ethyl substituent) is metabolised “by omega- and omega-1-oxidation to yield polar metabolites capable of excretion in the urine. At high-dose levels these oxidation pathways may be saturated, in which case, the corresponding acid may undergo conjugation with glucuronic acid.” (WHO FOOD ADDITIVES SERIES 40, 1998)

According to WHO FOOD ADDITIVES SERIES 32 (1993), 2-Ethylhexanol is rapidly excreted. Thus, bioaccumulation is unlikely to occur. 

 

References

WHO FOOD ADDITIVES SERIES 32 (1993)2-ETHYL-1-HEXANOL. Available online:

http://www.inchem.org/documents/jecfa/jecmono/v32je04.htm

WHO FOOD ADDITIVES SERIES 40 (1998)SATURATED ALIPHATIC ACYCLIC BRANCHED-CHAIN PRIMARY ALCOHOLS, ALDEHYDES, AND ACIDS.

Available online: http://www.inchem.org/documents/jecfa/jecmono/v040je11.htm