Reaction mass of Phenol, dodecyl-, sulfurized, calcium salts and benzene and butene and calcium carbonate and calcium dihydroxide and sulphur trioxide

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.

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Additional information

TEST MATERIAL

The substance is solid in it's pure form, however all testing has been conducted on a sample of the neat substance with refined mineral oil (approx 60% EC 903-161 -3 and 40% refined mineral oil). This was deemed the most appropriate sample to test as the material will be exclusively present in solvent oil during synthesis and handling.

TOXICOKINETICS ASSESSMENT

There were no toxicokinetic studies that directly addressed absorption, distribution, metabolism, or excretion of EC-903 -161 -3. However, information is available from existing toxicology studies and the physical chemical properties to infer potential toxicokinetic properties.

 

Significance of Route of Exposure

Dermal route: This is considered the principle route for occupational exposure. 

Oral route: This is not considered a relevant route for occupational exposure or the general population. Slight exposure may occur via accidental hand-to-mouth contact, but this isn’t expected to contribute significantly to exposure.

 Inhalation route: Under conditions of normal handling and use, the registered substance will not be aerosolized and, based on its physico-chemical properties, there is negligible potential for volatilisation and inhalation exposure.

 

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, it is expected the majority of components will be larger than 500 g/mole, which is the generally accepted limit for size exclusion by the skin.

EC 903-161-3 is very lipophilic, with a log K_ow>6.33. Maximum absorption is generally between log K_ow1 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 is approximately <0.5 mg/L. This indicates that the Registration substance is likely to have very low solubility in water, thus further decreasing the potential for complete penetration. The material is exclusively synthesised and handled in base oil, 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. 

An acute dermal study conducted on EC-903-161-3 did not show any evidence that the material was dermally absorbed as no signs of toxicity were seen in any aspect of the study. The Local Lymph Node Assay on material EC 903-161-3 was negative, but the results suggest that some test material or component may be getting absorbed through the skin.

Oral Route: The same physical and 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 registered substance are not favourable for GI absorption. However it is possible that a very small percentage of components of the UVCB registration material maybe of low enough molecular weight to favour absorption across the GI tract. Results obtained from acute animal toxicity tests in which the Registration substance was administered via oral gavage and in which acute toxicity was not observed (i.e., LD50s were greater than 2000 mg/kg) provide no evidence of significant absorption across the GI tract. A sub-acute study conducted on the Registration substance showed a low order of toxicity (i.e., minimal effects at 1000 mg/kg/day), again providing 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 903-161-3 is absorbed and whether it partitions into any specific tissues.

METABOLISM

The results of the sub-acute 28-day oral toxicity study 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 21% degradation occurred over 28 days in the ready biodegradation study, and this was attributed to both biotic and abiotic degradation. Therefore, no data exist to suggest that EC 903-161-3 is significantly metabolised within the body.

 

EXCRETION

There is no data to indicate the main route of excretion but poorly water soluble products 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.