Phenol, paraalkylation products with C12-rich branched olefins derived from propene oligomerisation, reaction products with sulphur monochloride and decene, reaction products with Benzoic acid, 2-hydroxy-,C14-18 alkyl dervis., polybutenyl benzenesulphonic acid, carbon dioxide and calcium hydroxide

Endpoint summary

Description of key information

Short description of key information on bioaccumulation potential result:
An assessment of the toxicokinetic behaviour of the substance has been conducted to the extent that can be derived from relevant available information.

Additional information

Test Material

The Registration substance is solid in its pure form, however all testing has been conducted with the Registration substance in refined mineral oil (59.2% EC 903-162-9 and 40.8% refined mineral oil). This was appropriate as the Registration substance is exclusively synthesised and handled in solvent oil.

Toxicokinetic Assessment

There were no toxicokinetic studies that directly addressed absorption, distribution, metabolism or excretion of EC 903-162-9. However, information is available from existing toxicology studies and the physico-chemical properties to infer potential toxicokinetic properties.

 

Absorption

Dermal Route: According to ECETOC Monograph 20: Percutaneous Absorption, the physical chemical properties that influence dermal absorption are molecular weight, water and lipid solubility, and degree of ionization. The molecular weight of the substance is variable given that it is a UVCB; however, based on knowledge of the starting materials and reaction conditions combined with qualitative spectra and mass balance calculations, it is expected that the majority of the organic constituents will be larger than 500 g/mole, which is the generally accepted limit for size exclusion by the skin. It is likely that the registration substance will also contain a very small percentage of organic constituents that are of low enough molecular weight that dermal absorption would not be hindered by molecular size.   EC 903-162-9 is very lipophilic, with an experimentally measured log K_ow>6.33, and a notably higher true log Kow (>10) expected and supported by QSAR modelling (see IUCLID Section 4.7). Maximum absorption is generally between log K_ow 1 and 2 and therefore the substance is too lipophilic to be readily absorbed. This is because the penetrant has to be lipophilic enough to cross the lipophilic portion of the membrane, but hydrophilic enough to pass the hydrophilic portion. The water solubility of this substance has been experimentally measured as <0.5 mg/L and is likely to be much lower. The very low solubility in water further decreases the potential for complete systemic absorption. The material is exclusively synthesised and handled in base oil and it is considered the material will preferentially remain within this solvent and is unlikely to favour partitioning into the stratum corneum. Based on these physical chemical properties, this material is predicted to be absorbed very slowly and no significant systemic uptake is expected. A read-across acute dermal toxicity study conducted using an analogue material did not show any evidence that the material was dermally absorbed as no signs of toxicity were seen in any aspect of the study.

Oral Route: The same physical chemical factors that affect dermal absorption also affect absorption from the gastrointestinal (GI) tract. The difference being that log K_ow between 0 and 4 are optimal for GI absorption. The high lipophilicity, low water solubility, and large molecular weight of the Registration substance are not favourable for GI absorption. However, a very small percentage of the organic constituents may be of low enough molecular weight that absorption would not be hindered by molecular size and absorption may be favoured.

 

Results obtained from acute animal toxicity tests in which the Registration substance was administered via oral gavage and in which no toxicity was observed (i.e., LD50s were greater than 2000 mg/kg) provide no evidence of significant absorption across the GI tract. A sub-acute read-across study conducted on an analogue substance showed a low order of toxicity (i.e., minimal effects at 1000 mg/kg/day, which were predominantly GI tract related), again provided no evidence of significant absorption across the GI tract.

 

Distribution

 

Some of the factors that affect absorption will also affect the distribution of chemicals within the body. In general, the more lipophilic the substance, the more readily it will move into the tissues, especially fatty tissues and the more highly perfused tissues such as heart, liver and kidney. Plasma protein binding can influence the movement of chemicals from blood to tissue, however no information on the materials ability to bind to plasma proteins is available. No tissue effects were seen in any of the in vivo studies conducted therefore it is not clear whether EC 903-162-9 is absorbed and whether it partitions into any specific tissues

 

Bioaccumulation: No in vivo bioaccumulation data are available; however, QSAR modelling predicts the substance has a very low potential to bioaccumulate (see IUCLID section 5.3).

 

Metabolism

 

The results of the sub-acute oral toxicity study conducted on an analogue material show no evidence of an adaptive response in the livers of rats, which is normally associated with enhanced metabolism. The results of the in vitro genotoxicity assays do not show any evidence that addition of the S9 metabolising system either enhances or diminishes the activity of the substance and therefore does not give any indication as to whether the material is metabolised. It was not possible to ascertain the hydrolytic stability of the material as it is of very low water solubility. However, approximately 25% degradation occurred over 28 days in the ready biodegradation study, and this was attributed to both biotic and abiotic degradation. Therefore no data exists to suggest that EC 903-162-9 would be significantly metabolised if absorbed into the body.

 

Excretion

 

There is no data to indicate the main route of excretion but poorly water soluble materials with high molecular weight are unlikely to be excreted in the urine. Therefore, if material is absorbed and is not extensively metabolised, biliary excretion may be a significant route for this material. Any test material that is not absorbed will be excreted in the faeces.