Decanoic acid, mixed esters with octanoic acid and pentaerythritol

Endpoint summary

Description of key information

Oral (OECD 408, rat): NOAEL ≥ 1000 mg/kg bw/day

Inhalation (similar to OECD 413, rat): NOAEC = 0.5 mg/L

Dermal (similar to OECD 411, rat): NOAEL ≥ 2000 mg/kg bw/day

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

JUSTIFICATION OF THE READ-ACROSS ANALOGUE (RA-A) APPROACH

The target substance Tetraesters of 2,2-bis(hydroxymethyl)propane-1,3-diol and decanoic and octanoic acid (CAS No. 68441-68-9) is an ester of pentaerythritol and fatty acids of a chain length of C8 and C10. The analogue approach covers 10 source substances, all of them are polyol esters covering a variety of polyols (pentaerythritol, dipentaerythritol and trimethylolpropane) and fatty acid moieties (linear: C5-18; branched: C5, C8 and C9; unsaturated: C18:1, C18:2 and C18:3).

The available data allows for an accurate hazard and risk assessment of all source substances and the target substance. Therefore, the read-across analogue (RA-A) approach is applied for the assessment of human health hazards of the target substance. Potential human health effects of the target substance are predicted by using adequate and reliable data for source substances within the analogue approach in accordance with Annex XI, Item 1.5, of Regulation (EC) No 1907/2006. In particular, for each specific endpoint the source substance(s) structurally closest to the target substance is/are chosen for read-across, with due regard to the requirements of adequacy and reliability of the available data. Structural similarities and similarities in properties and/or activities of the source and target substance are the basis of read-across.

A detailed justification of the read-across is provided in IUCLID section 13.

Target and source substances covered by the RA-A approach:

ID	CAS No.	EC No.	Chemical name	Fatty acid chain length	Type of alcohol	Degree of esterification	Molecular Formula	MW [g/mol]
Target	68441-68-9	270-472-2	Decanoic acid, mixed esters with octanoic acid and pentaerythritol	C8, C10	PE	Tetra	C37H68O8; C45H84O8	640.93 - 753.14
Source 1	11138-60-6	234-392-1	Fatty acids, C8-10 (even numbered), di- and triesters with propylidynetrimethanol	C8, C10	TMP	Tri	C30H56O6; C36H68O6	512.78 - 596.94
Source 2	15834-04-5	239-937-7	2,2-bis[[(1-oxopentyl)oxy]methyl] propane-1,3-diyl divalerate	C5	PE	Tetra	C25H44O8	472.62
Source 3	71010-76-9	275-118-0	Decanoic acid, mixed esters with heptanoic acid, octanoic acid, pentaerythritol and valeric acid	C5, C5iso, C6, C7, C8, C9, C10	PE	Tetra	C25H44O8; C33H60O8; C45H84O8	472.62 - 753.14
Source 4	146289-36-3	--	Pentaerythritol ester of pentanoic acids and isononanoic acid	C5, C5iso, C9branched	PE	Tetra	C25H44O8; C41H76O8	472.62 – 697.04
Source 5	68424-31-7	270-291-9	Pentaerythritol tetraesters of n-decanoic, n-heptanoic, n-octanoic and n-valeric acids	C5, C7, C8, C10	PE	Tetra	C25H44O8; C45H84O8	472.62 – 753.14
Source 6	85536-35-2	287-517-7	Fatty acids, C5-9, mixed esters with dipentaerythritol and pentaerythritol	C5-9	PE and DiPE	Tetra and Hexa	C25H44O8; C41H76O8; C40H70O13; C60H110O13	472.62 - 1039.51
Source 7	68604-44-4	271-694-2	Fatty acids, C16-18 and C18-unsatd., tetraesters with pentaerythritol	C16, C17, C18, C18:1, C18:2, C18:3	PE	Tetra	C69H132O8; C77H148O8; C77H104O8	1089.78 - 1193.93
Source 8	189200-42-8	--	Fatty acids, C8-10 mixed esters with dipenaterythritol, isooctanoic acid, pentaerythritol and tripentaerythritol	C8-10, C8iso	PE and DiPE	Tetra	C37H68O8; C45H84O8; C41H76O8; C58H106O13; C70H130O13; C64H118O13	640.93 – 1179.77
Source 9	67762-53-2	267-022-2	Carboxylic acids, C5-9, tetraesters with pentaerythritol	C5-9	PE	Tetra	C25H44O8; C41H76O8	472.62 - 697.04
Source 10	85586-24-9	287-827-2	Fatty acids, C8-10, tetraesters with pentaerythritol	C8-10	PE	Tetra	C37H68O8; C45H84O8	640.93 - 753.14

DISCUSSION

No data on repeated dose toxicity are available for the target substance Tetraesters of 2,2-bis(hydroxymethyl)propane-1,3-diol and decanoic and octanoic acid (CAS No. 68441-68-9). Therefore, inhalation and dermal repeated dose toxicity information was read-across from the source substance Carboxylic acids, C5-9, tetraesters with pentaerythritol (CAS 67762-53-2). The source substance Pentaerythritol ester of pentanoic acids and isononanoic acid (CAS 146289-36-3) has been used to derive appropriate data for the repeated dose toxicity via the oral route of exposure.

Repeated dose toxicity: oral

A reliable sub-chronic oral repeated dose toxicity study (90-day) with Pentaerythritol ester of pentanoic acids and isononanoic acid (CAS 146289‑36-3) was performed according to OECD TG 408 (Emery, 1998) in rats. The daily oral administration of the test substance was tolerated without any adverse effects up to and including the highest dose tested (1000 mg/kg bw/day). The observed increase in kidney weights in all male animals could be correlated to the formation of hyaline droplets a phenomenon widely accepted to be specific to male rats and as such considered to have no relevance to man. Thus, a 90-day oral NOAEL of 1000 mg/kg bw/day was derived in male and female rats.

Repeated dose toxicity: inhalation

A reliable sub-chronic inhalation repeated dose toxicity study (90-day) with Carboxylic acids, C5-9, tetraesters with pentaerythritol (CAS 67762-53-2) was performed equivalent or similar to OECD TG 413 (Exxon, 1992). Briefly, no substance-related adverse effects were observed for body weight, body weight gain, mortality, clinical biochemistry and haematological parameters. The lungs of the high dose animals revealed a minimal increase in weight which correlated with slightly increased numbers of macrophages in the pulmonary alveoli. Based on the results of the study and the absence of any toxicological relevant findings the sub-chronic NOAEC is considered to be 0.5 mg/L air for male and female rats.

Repeated dose toxicity: dermal

A reliable sub-chronic dermal repeated dose toxicity study (90-day) with Carboxylic acids, C5‑9, tetraesters with pentaerythritol (CAS 67762-53-2) was performed equivalent or similar to OECD TG 411 (Exxon, 1988). In summary, no adverse effects were found after dermal application of the test substance for 90 days on the parameters investigated. Both test groups (800 and 2000 mg/kg bw/day) exhibited minimal erythema and flaking of the skin during the dosing phase. At microscopic examination it was identified as very minor epidermal hyperplasia and chronic inflammation of the superficial dermis. Since no effects of systemic toxicity were identified up to the highest dose tested, the 90-day dermal NOAEL was found to be 2000 mg/kg bw/day in male and female rats.

CONCLUSION

Based on the available data on source substances, no hazard for oral, dermal and inhalation repeated dose toxicity is expected for the target substance.

Justification for classification or non-classification

According to Article 13 of Regulation (EC) No. 1907/2006, information on intrinsic properties of substances may be provided by means other than tests e.g. by transferring information of structurally related substances to a target substance,

provided that conditions set out in Annex XI are met. Annex XI, sec. 1.5, states that “Substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or ‘category’ of substances. (...) This avoids the need to test every substance for every endpoint".

Therefore, Article 13 and Annex XI of Regulation (EC) No. 1907/2006 define the read-across concepts:

(i) read-across based on grouping of substances (category approach) - RA-C approach

(ii) read-across from supporting substance (structural analogue or surrogate) - RA-A approach.

Here the RA-A approach is applied to fill data gaps by transferring data from structural analogues to the target substance. As a result, unnecessary animal testing is avoided. Therefore, based on the analogue read-across approach, the available data on repeated dose toxicity do not meet the classification criteria according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.