Registration Dossier

Administrative data

Description of key information

Acute toxicity: Oral LD50 (rat, m/f): > 2000 mg/kg bw (OECD 423, GLP) 
Acute toxicity: Dermal LD50 (rat, m/f): > 2000 mg/kg bw (OECD 402, GLP)
Acute toxicity: Inhalation LC50 (rat, m/f): > 5.1 mg/L air (OECD 403, read-across from structural analogue)

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The study is GLP compliant and has a Klimisch score 1.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
5 100 mg/m³
Quality of whole database:
The key study and the supporting study have a Klimisch score 2.

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The study is a GLP compliant and has a Klimisch score 1.

Additional information

Justification for read-across approach

In accordance with Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met. In particular for human toxicity, information shall be generated whenever possible by means other than vertebrate animal tests", which includes the use of information from structurally related substances (grouping or read-across).

Having regard to the general rules for grouping of substances and read-across approach laid down in Annex XI, Item 1.5, of Regulation (EC) No 1907/2006, whereby toxicological properties may be predicted from data for reference substance(s) by interpolation to other substances on the basis of structural similarity, the following substances are selected as reference substances for assessment of toxicological endpoints, for which information gaps are identified.

Therefore, the analogue approach endpoint information for

-         acute toxicity via inhalation for Fatty acids, C5-10, esters with pentaerythritol (CAS 68424-31-7) and Fatty acids, C5-9, mixed esters with dipentaerythritol and pentaerythritol (CAS 85536-35-2)

-         the subchronic oral repeated dose toxicity for pentanoic acid, mixed esters with pentaerythritol, isopentanoic and isononanoic acid (CAS No. 146289-36-3);

-         the genetic toxicity information for pentaerythritol tetravalerate (CAS 15834-04-5) and Fatty acids, C5-10, esters with pentaerythritol (CAS 68424-31-7)

-         and information for developmental toxicity for Fatty acids C8-10, mixed esteres with diPE, isooctanoic acid, PE and triPe (CAS 189200-42-8) and Trimethylolpropane Caprylate Caprate (CAS 11138-60-6)

are used to predict the same endpoints for dipentaerythritol ester of nC5/iC9 acids (CAS No. 647028-25-9). The analogue substances are considered to be similar on the basis of structural similarity and similar properties and/or activities.

The structural similarities are based on:

(1) common functional groups: The source (reference) and target substances are all characterised by ester bond(s) between a polyol and one or more carboxylic fatty acid chains. The polyol moiety of the source and target substances comprises structurally related molecules: pentaerythritol, di-pentaerythritol, tri-pentaerythritol and trimethylolpropane, all of which share a neopentane backbone as underlying common molecular structure. The fatty acid moieties comprise saturated linear and/or branched chains of 5 to 10 C-atoms length.

(2) common precursors and the likelihood of common breakdown products via biological processes, which result in structurally similar chemicals. The source and target substances are all UVCB substances, except pentaerythritol tetravalerate (CAS 15834-04-5) which is a monoconstituent, produced by esterification of the corresponding polyol and fatty acid mixtures. Ester bond formation is in principle a reversible reaction (hydrolysis). A slow stepwise hydrolysis of the ester bonds by gastrointestinal enzymes is identified as the biological process, by which the breakdown of the source and target substances results in structurally similar chemicals: the respective polyol and fatty acid moieties as stated above.

(3) a constant pattern in the changing of the potency of the properties between source and target substances: For the source and target substances, the constant pattern is characterised by similarities in the potency of properties. The available data on the target and the source substances show similarities in physico-chemical properties, in particular the high molecular weight of the substances. The molecular weight of Dipentaerythritol ester of nC5/iC9 acids ranges from 983 to 1096 g/mol and molecular weights of the target substances ranges from 472.62 to 1039.5 g/mol. In addition, the octanol/water partition coefficient of Dipentaerythritol ester of nC5/iC9 acids is > 6.2 (Lumsden, 2000) and available data on the calculated partition coefficients of the target substances are in the range of 6.74 to 13.59 (as published in respective dossiers on ECHA homepage). Furthermore, the target substance has a low water solubility (see toxicokinetics) and calculated water solubility of the source substances is considered to be low as well (Lumsden, 2000).

The available data on toxicological properties indicate that the source and target substances have a similar toxicokinetic behaviour; especially they are assumed to be slowly hydrolyses (see toxicokinetics). In addition, a low acute oral toxicity was seen for the source substance as well as for Trimethylolpropane Caprylate Caprate and Fatty acids, C5-10, esters with pentaerythritol (as published in respective dossiers on ECHA homepage). A low acute inhalation toxicity for Fatty acids, C5-9, mixed esters with dipentaerythritol and pentaerythritol and Fatty acids, C5-10, esters with pentaerythritol was observed as well (Parr-Dobranski, 1994a,b). Dipentaerythritol ester of nC5/iC9 acids is not skin or eye irritating and have not shown sensitising properties (Allen, 1999a,b,c) and the same is true for the source substances Fatty acids, C5-10, esters with pentaerythritol and Trimethylolpropane Caprylate Caprate (as published in respective dossiers on ECHA homepage). A low toxicity after repeated oral exposure (NOAEL > 1000 mg/kg bw/day) were observed for the source substance and for Fatty acids, C5-10, esters with pentaerythritol (Jones, 2000; Brammer, 1993) and for pentanoic acid, mixed esters with pentaerythritol, isopentanoic and isononanoic acid (NOAEL = 300 mg/kg bw/day; Müller, 1998). In addition, the available data on genotoxicity show that Dipentaerythritol ester of nC5/iC9 acids and the target substance Trimethylolpropane Caprylate Caprate are not genotoxic in the bacterial reverse mutation assay or clastogenic (Thompson, 1992; Wright, 2000; as published in respective dossier on ECHA homepage) and the source substance pentaerythritol tetravalerate did not show genotoxicity in a mammalian cell gene mutation assay (Verspeek-Rip, 2010). The target substance, Fatty acids, C5-10, esters with pentaerythritol did not show clastogenic properties in vivo as well (Griffiths, 1992) and no effect on intrauterine development was seen for Trimethylolpropane Caprylate Caprate and Fatty acids C8-10, mixed esteres with diPE, isooctanoic acid, PE and triPe.

In summary, all available data on the source and target substances show that the constant pattern is characterised by a lack of potency of properties.

In order to avoid the need to test Dipentaerythritol ester of nC5/iC9 acids for every endpoint, the analogue concept (read-across approach) is applied for the assessment of human health hazards. Thus where applicable, human health effects are predicted from adequate and reliable data for the reference substances by interpolation to Dipentaerythritol ester of nC5/iC9 acids in accordance with Annex XI, Item 1.5 of Regulation (EC) No 1907/2006.

A detailed justification for the grouping of chemicals and read-across is provided in the technical dossier (see IUCLID Section 13) as well as in the Chemical Safety Report.

Oral

The acute oral toxicity of Dipentaerythritol ester of nC5/iC9 acids was evaluated in rats in accordance with OECD guideline 423 under GLP conditions (Allen, 1999).

A first group of 3 female Sprague-Dawley CD rats was initially dosed with 2000 mg/kg bw (2.06 mL/kg bw) of the test substance by gavage. The second group consisted of 3 male animals which were sequentially tested at the same dose level. The animals were observed for a period of 14 days following administration.

During the study period, no mortality and no clinical signs of toxicity occurred in any animal. No effect on body weight was noted. Necropsy revealed no substance-related findings. Therefore, the oral LD50 for male and female rats was considered to be greater than 2000 mg/kg bw (experimental value) and greater than 5000 mg/kg bw according to the cut-off value set in the OECD guideline 423.

Inhalation

No study investigating the acute toxicity via the inhalation route of Dipentaerythritol ester of nC5/iC9 acids is available. In order to fulfil the standard information requirements set out in Annex VII, 8.5, read-across from the reference substances Fatty acids, C5-10 (linear and branched and without 2-Ethylhexanoic acid), mixed esters with pentaerythritol (CAS 68424-31-7) and Fatty acids, C5-9, mixed esters with dipentaerythritol and pentaerythritol (CAS 85536-35-2) is conducted in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006 following an analogue approach.

A study with the analogue Fatty acids, C5-10 (linear and branched and without 2-Ethylhexanoic acid), was performed according to OECD 403 (Parr-Dobrzanski, 1994).

A group of 10 rats (5 males and 5 females) were exposed for 4 h to 5.1 mg/L aerosol of the test material. The animals were observed for a period of 14 days following administration. During the study period, no mortality and no systemic signs of toxicity occurred in any animal. Clinical signs included hunched posture, chromodacryorrhea, piloerection, stains around the nose and wet fur, which were all reversible. Body weight gain and lung weight were within normal ranges. Furthermore, no treatment related gross pathological findings were apparent in any animal. Therefore, the LC50 for male and female rats was considered to be greater than 5.1 mg/L air.

A study with Fatty acids, C5-9, mixed esters with dipentaerythritol and pentaerythritol, was performed according to OECD 403, as well (Parr-Dobrzanski, 1994).

A group of 10 rats (5 males and 5 females) were exposed for 4 h to 5 ± 0.22 mg/L air aerosol of the test material. The animals were observed for a period of 14 days following administration.

No mortality, no effects on body weight and no treatment related gross pathological findings were observed. Clinical signs were hunched posture, chromodacryorrhea, piloerection, stains around the nose and wet fur being reversible at the latest at Day 8. The LC50 for male and female rats was therefore considered to be greater than 5 mg/L air.

In conclusion, the LC50 for inhalation toxicity for male and female rats was considered to be greater than 5.1 mg/L air.

 

Dermal

The acute dermal toxicity of Dipentaerythritol ester of nC5/iC9 acids was evaluated in rats in accordance with OECD guideline 402 under GLP conditions (Allen, 1999).

A group of 10 Sprague-Dawley CD rats (5 per sex) was treated with 2000 mg/kg bw. The test substance was applied the clipped skin of the test animals covering 10% of the total body surface area for 24 h under semiocclusive conditions. The test animals were observed for a period of 14 days following application. No mortality occurred and no clinical signs of toxicity were apparent during the study period in any animal. No abnormal changes in body weight gains were observed in any animal. Necropsy revealed no substance-related findings and no signs of skin irritation were noted during the study period in any animal.

Therefore, the dermal LD50 for male and female rats was considered to be greater than 2000 mg/kg bw.


Justification for selection of acute toxicity – oral endpoint
Only one study available.

Justification for selection of acute toxicity – dermal endpoint
Only one study available.

Justification for classification or non-classification

The available data on the acute oral and dermal toxicity of Dipentaerythritol ester of nC5/iC9 acids does not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and the data are therefore conclusive but not sufficient for classification.
Based on read-across from the structurally similar substances Fatty acids, C5-10 (linear and branched and without 2-Ethylhexanoic acid), mixed esters with pentaerythritol and C5-9, mixed esters with dipentaerythritol and pentaerythritol, the available data on the acute toxicity via inhalation do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and the data are therefore conclusive but not sufficient for classification.