Decanoic acid, mixed esters with octanoic acid and pentaerythritol

Endpoint summary

Description of key information

Skin, rabbit (OECD 404): not irritating

Eye, rabbit (OECD 405): not irritating

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

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

Skin irritation / corrosion

The following 3 investigations for skin irritation / corrosion of the target substance are available.

Decanoic acid, mixed esters with octanoic acid and pentaerythritol (CAS No. 68441-68-9) has been investigated for its skin irritation / corrosion potential in a study performed according to OECD TG 404 and under GLP conditions (key, 68441-68-9, 1989). 0.5 mL of the neat test substance was applied to the clipped skin of 3 New Zealand White rabbits and kept under semiocclusive conditions for an exposure duration of 4 h. The overall observation period was 72 h with readings for skin reaction after 1, 24, 48 and 72 h. At the 1-h reading a slight erythema formation was observed in all 3 animals (score 2 in 1 animal and score 1 in the other two animals), which was fully reversible within 48 h after test substance application in 2/3 animals. The third animal showed no signs of erythema at the 72 h reading. The 24/48/72 h erythema mean score values determined have been 0.33 for animal #1, 0 for animal #2 and 0.66 for animal #3. No edema reaction was observed at any time in any animal over the complete duration of the test. Therefore, the test substance was not considered to be irritating to the skin in this study.

A human patch test was conducted to assess the irritation potential of Decanoic acid, mixed esters with octanoic acid and pentaerythritol (CAS 68441-68-9) to the skin of 11 human volunteers from the general population (Stearinerie, 2004). Only limited details are reported. The test substance was applied under occlusive conditions to the upper back of human volunteers and the skin reactions were recorded. None of the human volunteers showed any skin reaction at the end of the study period and the primary skin irritation index was considered to be 0. Thus, the test material is not considered to be irritating to human skin.

Additionally, a primary dermal irritation study was performed according to OECD Guideline 404 and GLP (BASF, 1991). The shaved skin of three male Kleinrussen, Chbb:HM rabbits was exposed to 0.5 mL unchanged test material for 4 hours under semiocclusive conditions. Skin reactions were assessed 1, 24, 48 and 72 hours after removal of the test substance. At the 24 h reading, very slight erythema was observed in all 3 animals (score 1), which was fully reversed 48 h after test substance removal. All treated skin sites appeared normal at the 72 hour observation. The 24/48/72 h mean erythema score was 0.33 for all animals, while edema scores were zero in all animals after 24, 48 and 72 h treatment. The test material was not considered irritating to the skin in this study.

Eye irritation / severe eye damage

There are two in vitro eye irritation studies available for the target substance. For both studies only limited reporting is available and both studies are therefore not considered reliable enough to be used in the hazard assessment. The test substance was investigated for its eye corrosion potential in vitro in a HET-CAM assay (Stearinerie, 2004a). The chorioallantoic membranes of chicken eggs were exposed to the test substance. The irritation score was reported to be 0. Thus, the test material was not considered corrosive to the eyes in this test. No indication to the irritation potential was possible. The second study investigated the test substance for its cytotoxicity in fibroblasts (Stearinerie, 2004a). The Ocular Irritation Index in fibroblasts (IOeq) based on cytotoxicity was found to be 0.5. Since no data are given on interpreting this index the result is considered to be inconclusive.

In addition, further supporting information is read across from the relevant source substances Fatty acids C8-10, mixed esters with dipentaerythritol, isooctanoic acid, pentaerythritol and tridipentaerythritol (CAS 189200-42-8), Fatty acids, C5-10, esters with pentaerythritol (CAS 68424-31-7).

Fatty acids C8-10, mixed esters with dipentaerythritol, isooctanoic acid, pentaerythritol and tridipentaerythritol (CAS 189200-42-8) was tested for its acute eye irritation potential in a study performed comparable to OECD Guideline 405 under GLP conditions (ExxonMobil, 1995). The undiluted test material (0.1 mL) was applied into the conjunctival sac of 6 (5 male and 1 female) New Zealand White rabbits each. The animals were observed for 7 days and reactions were assessed 1, 24, 48, 72 hours and 7 days after instillation according to the Draize scoring system. One hour after instillation of the test substance, slight conjunctival redness and chemosis were observed in all animals. Scores for conjuntival redness at the 1-h reading were 3 in 1 animal, 2 in 4 animals and 1 in the last animal. Chemosis scores at the 1-h reading were 1 in 2 animals and 2 in the remaining 4 animals. Chemosis was reversible within 24 hours whereas conjunctival redness was reversible in all animals within 7 days. The mean 24/48/72 h conjuctival redness scores were as follows: 0.33 for animal #1, 0.66 for animals #2 and #5, 0 for animals #3 and #4, 1 for animal #6. The 24/48/72 h chemosis mean score of all animals was 0. No effects on the iris of any animal was observed at any time point throughout the entire experiment. Fluorescein staining of the cornea was observed in three animals at the 48 h reading time point. At the 72 h reading, no staining of the cornea was observed indicating that the corneal response was superficial and transient. Thus, the test material is not considered irritating to the eyes under the conditions of this study.

Fatty acids, C5-10, esters with pentaerythritol (CAS 68424-31-7) was tested for its acute eye irritation potential in a study performed comparable to OECD Guideline 405 (WoE, RA-A, 68424-31-7, 1991). The undiluted test material (0.1 mL) was applied into the conjunctival sac of three female New Zealand White rabbits each. The animals were observed for three days and reactions were assessed 1, 24, 48 and 72 hours after instillation according to the Draize scoring system. No corneal or iridial effects were observed. Conjunctival effects included slight redness (1 animal) and slight discharge (1 animal) and were transiently seen approximately 1 h after dosing. All 24/48/72 h mean scores for all animals were 0. Thus, the test material is not considered irritating to the eyes in this study.

CONCLUSION

The available data on either the target substance itself or suitable source substances did not show any skin or eye irritation effects. Therefore, the target substance is not predicted to be a skin irritant or an eye irritant.

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/source substances to the target substance. As a result, unnecessary animal testing is avoided. Therefore, based on data available for the target and analogue substances, the available data on skin and eye irritation do not meet the classification criteria according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.