Registration Dossier

Administrative data

Description of key information

Acute toxicity: Oral LD50 (rat, m/f): > 2000 mg/kg bw (OECD 401, analogue approach)
Acute toxicity: Dermal LD50 (rat, m/f): > 2000 mg/kg bw (OECD 402, analogue approach)
Acute toxicity: Inhalation LC50 (rat, m/f): > 5.1 mg/L air (OECD 403, analogue approach)

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises adequate, reliable (Klimisch score 2) studies from reference substances with similar structure and intrinsic properties. Read-across is justified based on common origin, common precursors and breakdown products of hydrolysis and consistent trends in e toxicological profile (refer to endpoint discussion for further details).
Taken together, the information from these independent sources is consistent and provides sufficient weight of evidence for hazard assessment leading to an endpoint conclusion in accordance with Annex XI, 1.2, of Regulation (EC) No 1907/2006. Therefore, the available information as a whole is sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises adequate, reliable (Klimisch score 2) studies from reference substances with similar structure and intrinsic properties. Read-across is justified based on common origin, common precursors and breakdown products of hydrolysis and consistent trends in e toxicological profile (refer to endpoint discussion for further details).
Taken together, the information from these independent sources is consistent and provides sufficient weight of evidence for hazard assessment leading to an endpoint conclusion in accordance with Annex XI, 1.2, of Regulation (EC) No 1907/2006. Therefore, the available information as a whole is sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises adequate, reliable (Klimisch score 2) studies from reference substances with similar structure and intrinsic properties. Read-across is justified based on common origin, common precursors and breakdown products of hydrolysis and consistent trends in e toxicological profile (refer to endpoint discussion for further details).
Taken together, the information from these independent sources is consistent and provides sufficient weight of evidence for hazard assessment leading to an endpoint conclusion in accordance with Annex XI, 1.2, of Regulation (EC) No 1907/2006. Therefore, the available information as a whole is sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Additional information

There are no data available for the acute toxicity of Fatty acids, C16-18 and C18-unsatd., hexaesters with dipentaerythritol (CAS# 68604-38-6). In order to fulfil the standard information requirements set out in Annex VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from structurally related substances was conducted.

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 substances may be predicted as similar provided that their physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity.

Overview for acute toxicity

CAS

Acute toxicity oral

Acute toxicity inhalation

Acute toxicity dermal

CAS 68604-38-6 (a)

Target substance

RA: CAS 19321-40-5

RA: CAS 68424-31 -7

RA: CAS 647028 -25 -9

RA: CAS 68424-31-7

RA: CAS 62125-22-8 

RA: CAS 647028 -25 -9

CAS 68424-31-7 (b)

LD50 > 2000 mg/kg bw

LC50 > 5.1 mg/L air

--

CAS 62125-22-8

--

--

LD50 > 2000 mg/kg bw

CAS 647028-25-9

LD50 > 2000 mg/kg bw

 

LD50 > 2000 mg/kg bw

CAS 19321-40-5

LD50 > 2000 mg/kg bw

--

--

 (a) Substances subject to the REACh Phase-in registration deadline of 31 May 2013 are indicated in bold font. Only for this substance a full set of experimental results and/or read-across is given.

 (b) Substances that are either already registered under REACh or not subject to the REACh Phase-in registration deadline of 31 May 2013 are indicated in normal font. Lack of data for a given endpoint is indicated by “--“.

The above mentioned substances are considered to be similar on the basis of structural similarity resulting in similar properties and/or activities. The available endpoint information is used to predict the same endpoints for Fatty acids, C16-18 and C18-unsatd., hexaesters with dipentaerythritol (CAS# 68604-38-6)

A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

Discussion

CAS 68604-38-6

There are no studies available assessing the acute oral, inhalation or dermal toxicity of Fatty acids, C16-18 and C18-unsatd., hexaesters with dipentaerythritol (CAS# 68604-38-6). However, an analogue approach read-across, in accordance to Regulation (EC) No. 1907/2006 Annex XI, 1.5, was applied using Pentaerythritol tetraoleate (CAS# 19321-40-5), Fatty acids, C5-10, mixed esters with pentaerythritol (CAS# 68424-31-7), Dipentaerythritol with Fatty acids, C5 and C9iso (CAS# 647028-25-9) and,

2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate) (CAS# 62125-22-8

based on molecular structure similarities and similarities in physicochemical properties to make a statement regarding acute toxicity values.

 

Acute Oral Toxicity

An acute oral toxicity study with Pentaerythritol tetraoleate (CAS# 19321-40-5) was performed according to OECD Guideline 423 (acute toxic class method, limit test) and GLP (Pels Rijcken, 1997). Pentaerythritol tetraoleate was administered by oral gavage to three Wistar rats at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15). No treatment related abnormalities were observed. The oral LD50 value in rats was found to exceed 2000 mg/kg bw.

 

A second acute oral toxicity study with Fatty acids, C5-10, esters with pentaerythritol (CAS# 68424-31-7) was performed comparable to OECD Guideline 401 (limit test) (Robinson, 1991). Pentaerythritol tetraoleate was administered by oral gavage to only 2 male and female Alderley Park SPF albino rats at 2000 mg/kg body weight. Animals were subjected to daily observations and determination of body weight. Macroscopic examination was performed after terminal sacrifice however, time frame until sacrifice is not given. No treatment related abnormalities were observed. The oral LD50 value in rats was found to exceed 2000 mg/kg bw.

 

The acute oral toxicity of Dipentaerythritol ester of nC5/iC9 acids (CAS# 647028-25-9) 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.

 

In summary, the LD50 for Fatty acids, C16-18 and C18-unsatd., hexaesters with dipentaerythritol was assumed to exceed 2000 mg/kg.

 

Acute Inhalation Toxicity

An acute inhalation toxicity study was performed with Fatty acids, C5-10, esters with pentaerythritol (CAS# 68424-31-7) comparable to OECD Guideline 403.

5 male and female Alpk:APfSD rats were exposed for 4 hours to 5.1 mg/L air test substance aerosol by nose only inhalation (Parr-Dobrzanski, 1994). The test substance caused no mortality, body weight changes or abnormalities in necropsy during the 15 day study period. Some clinical signs were noticed, which consisted of hunched position, chromodacryorrhea, piloerection, staining around nose and wet fur. These signs however occurred during or just after exposure and were clearly consistent with the use of restraint for exposure. The LC50 was therefore found to be greater than 5.1 mg/L air.

Acute Dermal Toxicity

An acute dermal toxicity (limit test) was performed on 2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate) (CAS# 62125-22-8) according to OECD Guideline 402 and GLP (Debets, 1984). 5 male and female Wistar rats were exposed to 2000 mg test substance/kg bodyweight for 24 hours on the back skin under occlusive 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 and necropsy at study termination revealed no abnormalities. Thus, the acute dermal LD50 in rats for pentaerythritol tetraisostearate was found to exceed 2000 mg/kg bw.

The acute dermal toxicity of Dipentaerythritol ester of nC5/iC9 acids (CAS# 647028-25-9) was evaluated in rats in an acute toxicity dermal study 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.

 

Conclusion for acute toxicity

In summary, three studies are available investigating the acute oral toxicity of Pentaerythritol tetraoleate (CAS# 19321-40-5), Dipentaerythritol ester of nC5/iC9 acids (CAS# 647028-25-9), and Fatty acids, C5-10, esters with pentaerythritol (CAS# 68424-31-7) resulting in oral LD50 values greater than 2000 mg/kg bw. For acute inhalation toxicity one study is available Fatty acids, C5-10, esters with pentaerythritol (CAS# 68424-31-7) having a LC50 value for rats of greater than 5.1 mg/L air. Acute dermal toxicity data with 2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate) (CAS# 62125-22-8) and Dipentaerythritol ester of nC5/iC9 acids (CAS# 647028-25-9) showed no effects at the limit dose of 2000 mg/kg bw.

Thus, the available data indicate a very low level of acute toxicity for the test substance and thus, no hazard for acute oral, inhalative and dermal toxicity was identified.


Justification for selection of acute toxicity – oral endpoint
Hazard assessment is conducted by means of read-across from structural analogues. All available studies are adequate and reliable based on the identified similarities in structure and intrinsic properties between source and target substances and overall quality assessment (refer to the endpoint discussion for further details).

Justification for selection of acute toxicity – inhalation endpoint
Hazard assessment is conducted means of read-across based on structural analogues. All available studies are adequate and reliable based on the identified similarities in structure and intrinsic properties between source and target substances and overall quality assessment (refer to the endpoint discussion for further details).

Justification for selection of acute toxicity – dermal endpoint
Hazard assessment is conducted by means of read-across based on a category approach. All available studies are adequate and reliable based on the identified similarities in structure and intrinsic properties between source and target substances and overall quality assessment (refer to the endpoint discussion for further details).

Justification for classification or non-classification

Based on read-across from structurally similar substances, the available data on oral, inhalation and dermal toxicity do not meet the classification criteria according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.