Registration Dossier

Administrative data

Description of key information

Acute toxicity: Oral LD50 (rat, m/f): > 2000 mg/kg bw (OECD 401, GLP, analogue approach)
Acute toxicity: Dermal LD50 (rat, m/f): > 2000 mg/kg bw (OECD 402, GLP, analogue approach)
Acute toxicity: Inhalation LC50 (rat, m/f): > 5.0 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 environmental fate, ecotoxicological and 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 due to read across) 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 environmental fate, ecotoxicological and 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 an adequate, reliable study (Klimisch score 2 due to read-across) from a reference substance 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 environmental fate, ecotoxicological and 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

Justification for grouping of substances and read-across

There are no data available for the acute toxicity of 2,2-bis[[(1-oxoisononyl)oxy]methyl]-1,3-propanediyl diisononanoate (CAS# 93803-89-5). 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 acute toxicity

 

CAS

Acute toxicity oral

Acute toxicity inhalation

Acute toxicity dermal

CAS 93803-89-5(a)

RA: CAS 84418-63-3

RA: CAS 146289-36-3

RA: CAS 68424-31-7

RA: CAS 85536-35-2

RA: CAS 131459-39-7

CAS 84418-63-3 (b)

LD50 > 2000 mg/kg bw

--

--

CAS 68424-31-7

LD50 > 2000 mg/kg bw

LD50 > 5.1 mg/L air

--

CAS 131459-39-7

--

--

LD50 > 2000 mg/kg bw

CAS 146289-36-3

LD50 > 2000 mg/kg bw

--

--

CAS 85536-35-2

--

LD50 > 5 mg/L air

--

 (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 the structural and similar properties and/or activities. The available endpoint information is used to predict the same endpoints for 2,2-bis[[(1-oxoisononyl)oxy]methyl]-1,3-propanediyl diisononanoate (CAS# 93803-89-5).

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

Discussion

Acute oral toxicity

Acute toxicology: oral

Since no studies investigating the acute oral toxicity with 2,2-bis[[(1-oxoisononyl)oxy]methyl]-1,3-propanediyl diisononanoate (CAS# 93803-89-5) are available, in accordance to Regulation (EC) No. 1907/2006 Annex XI, 1.5 a read-across from the structurally related analogue substances Isononanoic acid, mixed esters with dipentaerythritol, heptanoic acid and pentaerythritol (CAS# 84418-63-3) and Pentaerythritol ester pentanoic acids and isononanoic acid (CAS# 146289-36-3) was conducted.

CAS 84418-63-3

An acute oral toxicity study (limit test) according to OECD TG 401 was conducted with Isononanoic acid, mixed esters with dipentaerythritol, heptanoic acid and pentaerythritol (CAS# 84418-63-3; McCall, 1991). Groups of 5 ALpk:AP male and female mouse received a dose of 2000 mg /kg bw of test substance by gavage. The animals were observed for 8 days. No mortality and significant signs of systemic toxicity were seen during the observational period. All animals lost weight initially due to a predose fast but all had exceeded their initial body weight by Day 3 and weight gain continued until the end of the study. With regard to the gross pathology analysis a small number of abnormalities were observed. However these effects were considered as a spectrum of known background changes in this specific rat strain were considered to be not treatment related. Thus, the acute oral LD 50 in rats was determined to be greater than 2000 mg/kg bw.

CAS 146289-36-3

In addition a limit test was conducted with Pentaerythritol ester of pentanoic acids and isononanoic acid (CAS# 146289-36-3) according to OECD 401 and GLP compliant (Sterzel, 1991). 5 male and female Wistar rats were administered with 2000 mg/kg bw test substance in arachidis oil via gavage. No mortality occurred during the 14 day observation period. At the same time no clinical signs of toxicity and effect on body weight were observed up to the end of the observation period. Necropsy and histopathological examination revealed no substance-related findings. On the basis of the test results the LD50 was determined to be greater than 2000 mg/kg bw.

Acute toxicology: inhalation

Since no studies investigating the acute inhalation toxicity of 2,2-bis[[(1-oxoisononyl)oxy]methyl]-1,3-propanediyl diisononanoate (CAS # 93803-89-5) are available, in accordance to Regulation (EC) No. 1907/2006 Annex XI, 1.5 a read-across from the structurally related analogue substances 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) was conducted.

CAS 68424-31-7

An acute inhalation toxicity study (limit test) was performed with Fatty acids, C5-10, esters with pentaerythritol (CAS# 68424-31-7) according to OECD guideline 403 (Parr-Dobrzanski, 1994). Five rats per sex were exposed (nose only) to an aerosol of the test material with an analytical concentration of 5.10 mg/L air (nominal concentration was 5.0 mg/L) for an exposure duration of four hours. No mortality occurred during the 14 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 No effect on body weight was noted. Finally necropsy and histopathological examination revealed no substance-related findings. Thus, the LC 50 after acute inhalation of Fatty acids, C5-10, esters with pentaerythritol in male and female rats was found to be greater than 5.1 mg/L air.

CAS 85536-35-2

An acute inhalation toxicity study (limit test) was performed with Fatty acids, C5-9, mixed esters with dipentaerythritol and pentaerythritol (CAS# 85536-35-2) according to OECD guideline 403 (Parr-Dobrzanski, 1994). Five rats per sex were exposed (nose only) to an aerosol of the test material with an analytical concentration of 5. 0 mg/L air for an exposure duration of four hours. No mortality occurred during the 14 day study period. Clinical signs were seen during and/or immediately after exposure were 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. Finally necropsy and histopathological examination revealed no substance-related findings. Thus, the LC 50 after acute inhalation of Fatty acids, C5-9, mixed esters with dipentaerythritol and pentaerythritolin male and female rats was found to be greater than 5.0 mg/L air.

 

Acute toxicology: dermal

Since no studies investigating the acute dermal toxicity with 2,2-bis[[(1-oxoisononyl)oxy]methyl]-1,3-propanediyl diisononanoate (CAS# 93803-89-5) are available, in accordance to Regulation (EC) No. 1907/2006 Annex XI, 1.5, a read-across from the structurally related analogue substance 3,5,5-trimethylhexanoic acid mixed tetraesters with pentaerythritol and valeric acid (CAS# 131459-39-7) was conducted.

CAS 131459-39-7

The acute dermal toxicity potential 3,5,5-trimethylhexanoic acid mixed tetraesters with pentaerythritol and valeric acid (CAS# 131459-39-7) was investigated in limit test performed according to OECD guideline 402 (Allen, 1999) and GLP compliant. The back and flanks regions of five male and female Sprague-Dawley rats was treated with 2000 mg/kg bw test material under semiocclusive conditions. 24 hours after the dosing the treated area of skin was cleaned with distilled water and cotton wool. No mortality occurred and no clinical signs of toxicity were observed in any of the animals during the 14-day observation period. With regard to the body weight: male rats and chieved satisfactory body weight gains throughout the study. Necropsy and histopathological examination revealed no substance-related findings. The test substance had no effect on body weight.

Thus, the dermal LC50 after treatment with 3,5,5-trimethylhexanoic acid mixed tetraesters with pentaerythritol and valeric acid in male and female rats was found to be greater than 2000 mg/kg bw.

 

Conclusion for acute toxicity

In summary, two studies, in accordance to Regulation (EC) No. 1907/2006 Annex XI, 1.5, are available for acute oral and inhalation toxicity respectively. The acute oral toxicity studies resulted in oral LD50 values greater than 2000 mg/kg bw. For acute inhalation toxicity a LC50 value for rats of 5.0 mg/L was evaluated. Acute dermal toxicity data from one structurally related analogue substance, in accordance to Regulation (EC) No. 1907/2006 Annex XI, 1.5, is used and no effects at the limit dose of 2000 mg/kg bw were observed.

Thus, the available data, indicate a very low level of acute toxicity for 2,2-bis[[(1-oxoisononyl)oxy]methyl]-1,3-propanediyl diisononanoate (CAS# 93803-89-5) 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 from a structural analogue. The selected study is the most adequate and reliable study based on the identified similarities in structure and intrinsic properties between source and target substance 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.