Registration Dossier

Administrative data

Link to relevant study record(s)

Description of key information

The physico-chemical properties of the substance, and extensive toxicity studies in animals provide strong support in determining the ADME profile for this substance, and therefore may substitute for the experimentation of in vivo effects.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
50
Absorption rate - dermal (%):
10
Absorption rate - inhalation (%):
100

Additional information

With respect to molecular weight (>1600), low water solubility (20 mg/l), and Log Kow (10.5), it is concluded that the test material is minimally absorbed in the gastro-intestinal tract after oral administration. This is supported by the absence of systemic toxicity in the acute oral study (LD50> 5000 mg/kg). Additionally, available subchronic toxicity data from similar materials in the Epoxidized Oils and Derivatives Chemical Category do not indicate a concern. The oral absorption rate is therefore considered to be 50%.

Absorption via skin is expected to be very low, since its high molecular weight impedes skin permeability [Guidance Document on Dermal Absorption, European Commission; Health and Consumer Protection Directorate-General.Sanco/222/2000 rev. 7, March 19, 2004]. This is supported by the absence of systemic toxicity in the acute dermal study (LD50 > 2000 mg/kg). The dermal absorption rate is therefore considered to be 10%.

 

Inhalative exposure is of no relevance due to the low vapor pressure (too low to measure analytically). The inhalation absorption rate is considered to be 100% as a worst-case scenario.

 

An assessment of distribution can not be assumed from subacute toxicological study as no effects were observed at doses up to 1000 mg/kg/day in the key study for the similar material CAS # 61789 -01 -3 Fatty acids, tall-oil, epoxidized, 2 -ethylhexyl esters. Increased liver weights were observed, however in the absence of histopathology correlates this was considered an adaptive response.

The test material is assumed to be subject to the same metabolic processes as other fats resulting in the release of fatty acids and lesser substituted alcohols or glycerides. From SIDS, 2006: Lipase is an enzyme that assists in the breakdown and digestion of fat in the body. Pancreatic lipase works at the oil/water interface since triglycerides are insoluble. During metabolism in the GI tract, pancreatic lipase preferentially hydrolyzes triglycerides to

release the free fatty acids from the SN-1 and SN-3 (terminal) positions of the glycerol backbone. Other products of metabolism are mono- and diglycerides. The monoglycerides, diglycerides, and fatty acids can be absorbed...Further hydrolysis can also occur via carboxylesterase activity.

 

It can be assumed that elimination of the substance is relevent. Based on its physicochemical properties, bioaccumulation in exposed organisms is not expected.

Discussion on bioaccumulation potential result:

This substance is slightly soluble in aqueous milieu (water solubility 20 mg/L), and has a high molecule weight (>1600) outside the optimal window for intestinal/dermal absorption. The lack of adverse findings following oral dosing (LD50 > 5000 mg/kg for acute toxicity; NOAEL 1000 mg/kg/d for repeat dose toxicity), or dermal dosing (LD50 > 2000 mg/kg) may be at least partially due to limited gastrointestinal/dermal absorption of the test substance after treatment, and/or a very low index of inherent toxicity for this substance, and/or its metabolite(s).