Oligomerisation products of 2,2'-[(1-methylethylidene)bis(4,1-phenyleneoxymethylene)]bisoxirane with acrylic acid and fatty acids, C18-unsatd., dimers and nonanoic acid

Endpoint summary

Description of key information

There were no studies available in which the toxicokinetic properties of the test substance were investigated. However, as per REACH guidance document R7. C (2014), information on absorption, distribution, metabolisation and excretion may be deduced from the physicochemical properties.

Based on the physchem properties and the available toxicological data, the absorption by oral and dermal route is expected.

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

There are no published data which could be identified on the toxicokinetics of the test substance. However, as per REACH guidance document R7. C (2014), information on absorption, distribution, metabolism and excretion may be deduced from the physicochemical properties including:

-       Water solubility

-       Partition coefficient

-       Vapour pressure

-       Molecular weight

The test substance is a UVCB type of substance having a molecular weight of ~530.6 g/mol (range [430-982]). It is a liquid with a tested water solubility between 10.2-29 mg/L. Volatility was determined to be very low (<1.3 E-8 Pa) and has a limited lipophilic character (log Kow of the major components corresponding to 3).

Based on the results of the described toxicity studies, an indication of oral and dermal uptake of the test substance is given. Therefore the bioavailablity can be considered to be existent.

Taking into account the log Kow (3.0) and the water solubility (10.2 mg/L), accumulation of the test substance is considered to be unlikely.

The expected toxicokinetic behaviour is derived from the physicochemical properties and the results from the available toxicological/toxicokinetic publication following the guide given in the REACH guidance document 7c (2014):

 

Oral and GI absorption: Given thewater solubility the substance, it is likely to be less soluble in GI fluid. It can then be expected that the substance can be at least partially absorbed in the gastrointestinal system, due to its log Kow and molecular weight. Systemic effects were observed at the doses equal or higher than 900 mg/kg bw/day in the oral 28-day study, confirming the oral absorption of the test substance.

In absence of actual data, the worst-case value of 50% has been considered for the oral absorption.

 

Inhalation absorption:Given the moderate log Kow and the indication for oral absorption, possible systemic uptake of the test substance afterinhalationexposure is possible, although this would occur only when aerosol or vapour is created under particular conditions (e.g. spraying, elevated temperature/pressure).The worst-case value of 100% has been considered for the inhalation absorption.

 

 

Dermal absorption:

Dermal absorption of the test substance is expected to be slow due to binding to skin of the acrylate group. According to REACH guidance document R7.C (May 2014), dermal absorption is maximal for substances with molecular weights below 500 and log Kow values ranging between 1 and 2. The constituents of test substance have average molecular weights of ~530 g/mol and log Kows of 3.0 for the major constituents. This suggests that the substance may not penetrate very easily through skin. However, test substance is a skin sensitizer which suggests some extent of dermal absorption.Therefore, a worst-case value of 50% has been considered for the human dermal absorption.

 

Distribution:The physico-chemical information (molecular weight, lipophilicity and water solubility) indicates that the test substance could be distributed to many tissues. This is confirmed in the oral 28-day repeated toxicity study.

 

Accumulative potential:Based on the physico-chemical information (log Kow, structure not containing ionisable elements and water solubility), it is concluded that the potential for bioaccumulation is low.

 

Metabolism: No specific information could be found on metabolism, but evidence from other types of acrylates suggests that hydrolysis of the ester bond is likely to occur, producing acrylic acid and the corresponding alcohol, which are subsequently metabolised through normal metabolic routes. This hydrolysis is mediated by the ubiquitous tissues and circulating carboxylesterases. Another potential route of metabolism and detoxification may involve conjugation of the vinyl group of the acrylate with the sulfhydryl group of glutathione/GSH (i.e., glutathionation), with excretion as mercapturates.

Moreover, similar metabolic pathways were predicted via different metabolism simulators of OECD QSAR Tool box. The two simulators of the OECD Toolbox, predict either ester hydrolysis or oxidative O-dealkylation as first metabolic reactions (see below Table). Since oxidative O-dealkylation mainly occurs in the liver via cytochrome P-450 while the gastrointestinal tract is rich of esterases, ester hydrolysis is very likely the first metabolic reaction to occur. Upon ester hydrolysis, the common constituents of target and source substances - BADGEDA, BADGE-TA and (BisA_MonoGE)2EpoxyDA - would give rise to the same type of metabolites, including acrylic acid (CAS No. 79-10-7). The additional constituents of the target substance, which represent the 21% of the target substance (i.e. BADGE-MA-monononanoate and BADGE-DA-monononanoate), are also predicted to give rise to the same metabolites as BADGEM(D)A as well as to nonanoic acid (CAS No. 112-05-0), upon ester hydrolysis.

 

Excretion:Based on the physico-chemical information (average molecular weight of ~530 g/mol), metabolic pathways main excretion of the test substance can be expected to be similar to BADGEDA i.e., via urine.