Decanoic acid, mixed esters with octanoic acid and pentaerythritol

Endpoint summary

Description of key information

Oral: LD50 > 2000 mg/kg bw

Inhalation: LC50 > 4.06 mg/L

Dermal: LD50 > 2000 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via dermal route

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 acute toxicity are available for the target substance Decanoic acid, mixed esters with octanoic acid and pentaerythritol (CAS No. 68441-68-9). Therefore, oral and dermal acute toxicity was read-across from the source substance Decanoic acid, mixed esters with heptanoic acid, octanoic acid, pentaerythritol and valeric acid (CAS 71010-76-9). Read-across source substances Carboxylic acids, C5-9, tetraesters with pentaerythritol (CAS 67762-53-2) and Fatty acids, C5-9, mixed esters with dipentaerythritol and pentaerythritol (CAS 85536-35-2) have been used to derive appropriate data for the acute inhalation toxicity of the target substance.

Acute oral toxicity

An acute oral toxicity study with Decanoic acid, mixed esters with heptanoic acid, octanoic acid, pentaerythritol and valeric acid (CAS 71010-76-9) was performed according to OECD Guideline 425 (up and down procedure, limit test) and GLP (ExxonMobil, 2006). Decanoic acid, mixed esters with heptanoic acid, octanoic acid, pentaerythritol and valeric acid was administered by gavage to one female Sprague-Dawley rat at the starting dose of 2000 mg/kg bw. Since no mortality and no other toxic effects could be detected during the 14 day study period, 4 further female animals were equally dosed with 2000 mg/kg bw. No clinical signs of toxicity were observed up to the end of the 14-day observation period. No adverse effect on body weight was noted. Finally, necropsy revealed non substance-related findings. The oral LD50 value in female rats was found to exceed 2000 mg/kg bw.

Acute inhalation toxicity

The acute toxicity via the inhalation route of Fatty acids, C5-9 tetraesters with pentaerythritol (CAS 67762-53-2) has been investigated in rats in two studies. The first study was conducted comparable to OECD Guideline 403 and according to GLP. 10 male and female Sprague-Dawley rats were exposed for 4 hours to 0.48 or 4.06 mg/L test substance aerosol by whole body inhalation exposure (Exxon, 1990). No mortality, clinical signs, body weight changes or abnormalities in necropsy were observed during the 15-day study period in any group. The LC50 value was therefore found to be greater than 4.06 mg/L air.

In the second study 10 male and 5 female CD Sprague-Dawley rats were exposed for 4 hours to 5.5 mg/L test substance aerosol by nose/head only inhalation (Exxon, 1999). No mortalities occurred during the study period. Nasal discharge was noted as the only sign of clinical toxicity. The test group females (10/10) lost weight during the first week after the test material exposure, but gained weight during the second week after exposure. In 10/10 males no effect on body weight was noted. Necropsy examination revealed no substance-related findings. The LC50 value was therefore found to be greater than 5.50 mg/L air.

An acute inhalation toxicity study was performed with Fatty acids, C5-9, mixed esters with dipentaerythritol and pentaerythritol (CAS 85536-35-2) comparable to OECD Guideline 403. 5 male and female Alpk:APfSD rats were exposed for 4 hours to 5.0 mg/L test substance aerosol by nose only inhalation (WoE, RA-A, 85536-35-2, 1994). The test substance caused no mortality and no body weight changes during the 15 day study period. Clinical signs during and immediately after exposure included hunched posture, chromodacryorrhea, piloerection, stains around the nose and wet fur. In general, animals showed a rapid recovery from these effects by Day 2, although, hunched posture and piloerection persisted in few animals to Days 4 and 8, respectively. No effect on body weight was noted. Necropsy revealed non substance-findings. The LC50 value was therefore found to be greater than 5.0 mg/L air.

Acute dermal toxicity

An acute dermal toxicity study (limit test) was performed on Decanoic acid, mixed esters with heptanoic acid, octanoic acid, pentaerythritol and valeric acid (CAS 71010-76-9) comparable to OECD Guideline 402 and under GLP conditions (ExxonMobil, 2006a). 5 male and 5 female Sprague-Dawley rats were exposed to 2000 mg test substance/kg bodyweight for 24 hours on the back skin under semiocclusive conditions. The observation period was 14 days. No clinical signs of systemic toxicity were noted in any animal during the study period. Body weight gain was normal for this strain and age and necropsy at study termination revealed no abnormalities. Thus, the acute dermal LD50 value in rats for Decanoic acid, mixed esters with heptanoic acid, octanoic acid, pentaerythritol and valeric acid was found to exceed 2000 mg/kg bw.

CONCLUSION

The available data indicate a very low level of acute toxicity for the source substances and hence, no hazard for acute oral, inhalation and dermal toxicity is predicted 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/source substances to the target substance. As a result, unnecessary animal testing is avoided. Therefore, based on the analogue read-across approach, the available data on acute toxicity do not meet the classification criteria according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.