Reaction mass of 3-(octanoyloxy)propyl decanoate and propane-1,3-diyl didecanoate and propane-1,3-diyl dioctanoate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics, other

Remarks:

Expert Statement

Type of information:

other: Expert Statement

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Expert Statement, no study available

Data source

Reference

Reference Type:

other: Expert statement

Title:

Unnamed

Year:

2019

Report date:

2019

Materials and methods

Objective of study:

absorption

distribution

excretion

metabolism

Principles of method if other than guideline:

Expert statement

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of 3-(octanoyloxy)propyl decanoate and propane-1,3-diyl didecanoate and propane-1,3-diyl dioctanoate

EC Number:

684-597-9

Cas Number:

1072005-10-7

Molecular formula:

C19-23H36-44O4

IUPAC Name:

Reaction mass of 3-(octanoyloxy)propyl decanoate and propane-1,3-diyl didecanoate and propane-1,3-diyl dioctanoate

Test animals

Details on test animals or test system and environmental conditions:

not applicable

Administration / exposure

Duration and frequency of treatment / exposure:

not applicable

Positive control reference chemical:

not applicable

Details on study design:

not applicable

Details on dosing and sampling:

not applicable

Statistics:

not applicable

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

According to ECHA Guidance R.7c, the smaller the molecule the more easily it may be taken up via oral route (ECHA, 2014). Oral absorption is favoured for the test item as the molecular weight is below 500 g/mol. On the other hand, the low water solubility does not favour high absorption rates. Additionally, the test item is highly lipophilic (log Pow >4), therefore the uptake may be by micellular solubilisation. Taken together, the physiochemical properties indicate that the test item becomes sparsely bioavailable following the oral route. This assumption is supported by the results of the acute oral toxicity study in mice with the read across substance CAS 68583-51-7, where the highest concentration of 4600 mg/kg bw showed no effect.

The low water solubility of the substance does not favour high absorption rates. On the other hand, due to the good lipophilicity (log Pow values of 5.2 – 8.7) the uptake into the stratum corneum will be high, even if the rate of penetration may be limited by the rate of transfer between the stratum corneum and the epidermis. Besides that, dermal uptake is favoured for substances with a molecular weight < 100 g/mol. Therefore the molecular weight of the test item would not indicate absorption through skin. This is also supported by the results of the acute dermal toxicity study indicating no systemic signs up to 2000 mg/kg bw with the read across substance CAS 853947-59-8.


Due to the low volatility (vapour pressure <0.15 Pa and boiling point above 200°C) it is unlikely that the substance will be available as a vapour to a large extend, but if it is the case absorption via inhalation route is unlikely due to low water solubility and high log Pow value, disabling uptake directly across the respiratory tract epithelium by passive diffusion. The acute inhalation studies conducted with the read across substance CAS 68583-51-7 suggested a low potential for toxicity via inhalation (LC50 > 200ppm, equivalent to 5952 mg/m³).

Details on distribution in tissues:

In general, the smaller the molecule the wider the distribution. Based on the molecular weight (over 300 g/mol) and the liphophilicity (log Pow >4) it is assumed, that if absorbed, the test item is distributed into cells and not present in the blood.

Details on excretion:

According to the physicochemical properties of the substance, molecular weight, lipophilic characteristics and water solubility, urine excretion, breast milk, sweat and exfoliation are the main routes of elimination.

Metabolite characterisation studies

Details on metabolites:

During metabolism more polar substances are assumed to be formed to facilitate a more rapid excretion via urine. The main metabolism products are C8-10 and alcohols like 1,3 propanediol.

Applicant's summary and conclusion

Conclusions:

Bioaccumulation of the test substanceis not considered critical based on expert statement.

Executive summary:

Based on physicochemical characteristics, particularly water solubility and octanol-water partition coefficient, absorption by the oral and dermal route is expected. This assumption is further supported by the results of the oral and dermal acute toxicity studies, revealing no effects at very high doses. Absorption via inhalation route is unlikely, but can not be excluded. Bioaccumulation of the test item or its breakdown products will not occur.