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

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Justification for type of information:

A repeated dose toxicity study does not need to be conducted according to REACH Annex XI, 1.2, Weight of Evidence (WoE).

REACH Annex XI, 1.2. Weight of evidence states as follows:
“There may be sufficient weight of evidence from several independent sources of information leading to the assumption/conclusion that a substance has or has not a particular dangerous property, while the information from each single source alone is regarded insufficient to support this notion. (…)
Where sufficient weight of evidence for the presence or absence of a particular dangerous property is available:
— further testing on vertebrate animals for that property shall be omitted (…)”

There are no experimental data on mammalian toxicity available with the test item.

However, comprehensive data from structurally closely related substances is taken into account for assessment of the toxicological properties of the registered substance, according to REACH Annex XI, 1.5 (Read-Across). For respective read-across justification please refer to IUCLID Section 13.

Based on the available data with the read-across source substances, the target substance is considered to be of very low toxicity since no adverse effects were obtained in any of the toxicity studies conducted. None of the read-across substances require classification according to Regulation (EC) No 1272/2008 (CLP).
A QSAR Toolbox query (2019) with the three main components of the registered substance supports the above considerations. There were no structural alerts in regards to specific target organ toxicity, no categorization according to HESS and the Cramer class was predicted to be low (Class I).

Therefore, a risk assessment does not need to be conducted according to REACH Article 14(4) and DNEL derivation is not required.

Two pre-natal developmental toxicity studies are available with read-across substances. In both studies no adverse effects could be obtained up to the highest dose tested (i. e. 900 and 1000 mg/kg bw/d, respectively). Therefore, the NOAEL was determined to be the limit dose which is commonly applied for repeated dose toxicity, i. e. 1000 mg/kg bw/d. The treatment period in the pre-natal developmental toxicity study is shorter when compared to a subacute toxicity study (14 days vs. 28 days). However it should be taken into account that pregnant animals were administered being rather more susceptible to xenobiotics. Since no adverse effects were observed at all, it is considered very unlikely that a 14 days longer treatment period would lead to substantial adverse effects.

In addition to the hazard assessment the use profile of the registered substance should be taken in to account. The registered substance is only handled in controlled industrial settings making considerable exposure to humans unlikely. Assessment of toxicokinetic behaviour being based on physicochemical properties of the registered substance and toxicity data of the structural analogue substances concluded that the test items bioavailability will probably be very low, if not negligible. The registered substance is also applied in cosmetic products. Here, human health safety assessment of the final product is ensured under Cosmetics Regulation 1223/2009.

In conclusion and taking into account its low to negligible toxicity, the registered substance raises no concerns in regards to human health risk assessment that would justify a vertebrate repeated dose toxicity study. Neither as a hazard nor in regards to exposure considerations. Thus, conducting a repeated dose toxicity study in vertebrates is not justified. This is in line with REACH Article 25 (1) claiming that animal testing should always be the last resort.