Isononanoic acid, mixed esters with dipentaerythritol, heptanoic acid and pentaerythritol

Endpoint summary

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

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Basic data given

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

limited reporting, only 8 days observation

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: ALpk:AP

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: ICI Pharmaceuticlas, Alderley Park, Cheshire, UK
- Age at study initiation: approx. 6-10 weeks
- Weight at study initiation: 239 - 250 g (males); 184 - 202 g (females)
- Fasting period before study: 24 h
- Diet: ad libitum
- Water: ad libitum

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage): 10 mL/kg bw

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

other: not required

Details on study design:

- Duration of observation period following administration: 8 days
- Frequency of observations and weighing: prior to fasting, immediately prior dosing and at the end of the study
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

None of the animals died during the observation period of 8 days.

Clinical signs:

other: No significant signs of toxicity were observed.

Gross pathology:

There were a small number of gross abnormalities at post mortem (not further specified). These were part of a spectrum of known background changes seen in this rat strain and considered not to be treatment related.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified
DSD: not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises adequate, reliable (Klimisch score 2, partially 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 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 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 3,5,5 -trimethylanoic acid, mixed esters with dipentaerythritol . 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, the substances 3,5,5-trimethylhexanoic acid hexaester with dipentaerythritol (monoconstituent, CAS 844198-63-3), Pentaerythritol ester of pentanoic acids and isononanoic acid (CAS 146289-36-3), Fatty acids, C5-10, esters with pentaerythritol (CAS 68424-31-7), Fatty acids, C5-9, mixed esters with dipentaerythritol and pentaerythritol (CAS 85536-35-2), 3,5,5-trimethylhexanoic acid mixed tetraesters with pentaerythritol and valeric acid (CAS 131459-39-7) and Dipentaerythritol ester with fatty acids C5 and C9iso (CAS 647028-25-9) are selected as source for risk assessment. 

Acute toxicology: oral

Since no studies investigating the acute inhalation toxicity of 3,5,5 -trimethylhexanoic acid, mixed esters with dipentaerythritol (UVCB) are available, in accordance to Regulation (EC) No. 1907/2006 Annex XI, 1.5 a read-across to the structurally related analogue substance 3,5,5-trimethylhexanoic acid hexaester with dipentaerythritol (monoconstituent, CAS 844198-63-3), and pentaerythritol ester of pentanoic acids and isononanoic acid (CAS 146289-36-3) was conducted.

CAS 84418-63-3

One acute oral toxicity study is available for 3,5,5 -trimethylhexanoic acid, mixed esters with dipentaerythritol (monocostituent, CAS 84418-63-3). Although the study results were only given as a short summary, the results are considered adequate to assess the acute oral toxicity study of the test substance.

An acute oral toxicity study (limit test) according to OECD TG 401 was conducted with 3,5,5-trimethylhexanoic acid hexaester with dipentaerythritol (monoconstituent, CAS 84418-63-3; McCall, 1991). Groups of 5 ALpk:AP male and female rats 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 the predose fasting 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 LD50 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 LD 50 was determined to be greater than 2000 mg/kg bw.

 

Acute toxicology: inhalation

Since no studies investigating the acute inhalation toxicity of 3,5,5 -trimethylhexanoic acid, mixed esters with dipentaerythritol are available, in accordance to Regulation (EC) No. 1907/2006 Annex XI, 1.5 a read-across to 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 Fatty acids, C5-10, esters with pentaerythritol (CAS 68424-31-7) 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 pentaerythritol (CAS 85536-35-2) in 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 of 3,5,5 -trimethylhexanoic acid, mixed esters with dipentaerythritol are available, in accordance to Regulation (EC) No. 1907/2006 Annex XI, 1.5 a read-across to the structurally related analogue substance 3,5,5-trimethylhexanoic acid mixed tetraesters with PE and valeric acid (CAS 131459-39-7) and Dipentaerythritol ester of fatty acids C5 and C9iso (CAS 647028-25-9) 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 under GLP conditions. The back and flanks regions of five male and female Sprague-Dawley rats were treated with 2000 mg/kg bw test material under semiocclusive conditions. 24 h 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. Necropsy and histopathological examination revealed no substance-related findings. The test substance had no effect on body weight.

Thus, the dermal LD50 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.

CAS 647028-25-9

The acute dermal toxicity of Dipentaerythritol ester of fatty acids C5and C9iso (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, two studies are available for acute oral toxicity. It was conducted with the structurally similar substances 3,5,5-trimethylhexanoic acid hexaester with dipentaerythritol (monoconstituent, CAS 84418-63-3) and Pentaerythritol ester of pentanoic acids and isononanoic acid (CAS 146289-36-3) and resulted in oral LD50 values greater than 2000 mg/kg bw. For acute inhalation toxicity, two studies are available for 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). From these studies a LC50 value for male rats and female rat greater than 5.0 mg/L air was evaluated. Two acute dermal toxicity studies conducted with 3,5,5-trimethylhexanoic acid mixed tetraesters with pentaerythritol and valeric acid (CAS 131459-39-7), Dipentaerythritol ester of fatty acids C5and C9iso (CAS 647028-25-9) showed no effects at the limit dose 2000 mg/kg bw.

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

Justification for selection of acute toxicity – oral 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 – 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 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 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.