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Link to relevant study record(s)

Reference
Endpoint:
basic toxicokinetics, other
Remarks:
Theoretical assessment
Type of information:
other: Theoretical assessment
Adequacy of study:
supporting study
Study period:
March 2018
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Theoretical assessment of toxicokinetic properties
Objective of study:
toxicokinetics
Qualifier:
no guideline followed
Principles of method if other than guideline:
This theoretical assessment was prepared, taking all currently available relevant information into account, based on the REACH Guidance: Guidance on Information Requirements and
Chemical Safety Assessment, Chapter R.7c Endpoint specific guidance.
GLP compliance:
no
Conclusions:
A toxicokinetic assessment was performed based on the available data of the substance. Based on the physical/chemical properties of the substance, absorption factors for this substance are derived to be 10% (oral and dermal) and negligible for inhalation absorption for risk assessment purposes. The bioaccumulation potential is expected to be low.
Executive summary:

Upon exposure, a substance can enter the body via the gastrointestinal tract, the lungs and the skin. Since different parameters are relevant for absorption via the different routes of exposure, the three routes were addressed individually. After oral administration, in general, a compound needs to be dissolved before it can be taken up from the gastrointestinal tract. The water solubility of epoxypropyl neodecanoate, oligomeric reaction products with cyclohexane-1,2-dicarboxylic anhydride and propylidenetrimethanol is limited with 0.0103 mg/L, therefore it is expected that only traces will dissolve in the gastrointestinal fluids. In addition, the molecular weight is high (approx. 1282), which means that uptake via passive diffusion (passage of small water-soluble molecules through aqueous pores or carriage across membranes with the bulk passage of water) will be highly restricted. Epoxypropyl neodecanoate, oligomeric reaction products with cyclohexane-1,2-dicarboxylic anhydride and propylidenetrimethanol has a high partition coefficient (log Pow = >7.99), which implies that this substance preferably dissolves in lipids. In general, this property will allow a substance to cross epithelia by passive diffusion, however based on its high molecular weight this is not expected to take place. It is however possible that its high lipophilicity leads to micellular solubilisation under the influence of salts, which enables uptake via the lymphatic system. Furthermore, small amounts of the substance may be transported into epithelial cells by pinocytosis or persorption (passage through gaps in membranes left when the tips of villi are sloughed off). Epoxypropyl neodecanoate, oligomeric reaction products with cyclohexane-1,2-dicarboxylic anhydride and propylidenetrimethanol has at two ionisable hydroxyl groups, and although no data are available on the dissociation constant(s) of the substance, it can be expected to be present in ionized form. Under physiological circumstances (in the stomach or intestinal tracts) low to neutral pH circumstances are present, therefore epoxypropyl neodecanoate, oligomeric reaction products with cyclohexane-1,2-dicarboxylic anhydride and propylidenetrimethanol can be expected to be present in the ionised form at certain parts, which is expected to further hamper absorption.

Taken all data together it can be conclude that the uptake of epoxypropyl neodecanoate, oligomeric reaction products with cyclohexane-1,2-dicarboxylic anhydride and propylidenetrimethanol after oral exposure is expected to be limited by its very low water solubility, its high molecular size, and its expected presence in ionized form along the intestinal tract. On the other hand, the substance is highly lipophilic and may be able to penetrate biological membranes, it may form micelles, or it can be taken up via pinocytosis. Therefore, for risk assessment purposes oral absorption of epoxypropyl neodecanoate, oligomeric reaction products with cyclohexane-1,2-dicarboxylic anhydride and propylidenetrimethanol is set at 10%. The oral toxicity data do not provide reason to deviate from the proposed oral absorption factor. Once absorbed, distribution of the test substance throughout the body is expected to be low based on its limited water solubility and high molecular weight. Absorbed epoxypropyl neodecanoate, oligomeric reaction products with cyclohexane-1,2-dicarboxylic anhydride and propylidenetrimethanol is expected to be metabolized3. In general, lipophilic substances can accumulate in adipose tissue, which would result in a long biological half-live (high bioconcentration factor, BCF). However, there is general agreement that the rectilinear correlation between log BCF and log Pow fails for very hydrophobic chemical (log Pow > 6 -7), and that the bioconcentration is lower than expected.

Description of key information

A theoretical assessment of the toxicokinetic properties of the submission substance is available.

Key value for chemical safety assessment

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

Additional information

A toxicokinetic assessment was performed based on the available data of the substance. Based on the physical/chemical properties of the substance, absorption factors for this substance are derived to be 10% (oral and dermal) and negligible for inhalation absorption for risk assessment purposes. The bioaccumulation potential is expected to be low.