Pentaerythritol, mixed esters with linear and branched fatty acids

Endpoint summary

Description of key information

Oral (WoE): LD50 > 2000 mg/kg bw
Inhalation (WoE): LC50 > 5.1 mg/L
Dermal (WoE): LD50 > 2000 mg/kg bw

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) and consistent studies from reference substances with similar structure and intrinsic properties. Read-across is justified based on common precursors and breakdown products of hydrolysis and consistent trends in environmental fate, ecotoxicological and toxicological profile (refer to the 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 iwth 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 VIII, 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) and consistent studies from reference substances with similar structure and intrinsic properties. Read-across is justified based on common precursors and breakdown products of hydrolysis and consistent trends in environmental fate, ecotoxicological and toxicological profile (refer to the 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 iwth 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 VIII, 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) and consistent studies from reference substances with similar structure and intrinsic properties. Read-across is justified based on common precursors and breakdown products of hydrolysis and consistent trends in environmental fate, ecotoxicological and toxicological profile (refer to the 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 iwth 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 VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Additional information

Justification for analogue read-across

Data on the acute oral, inhalation and dermal toxicity of Pentaerythritol, mixed esters with linear and branched fatty acids are not available. The assessment of acute toxicity was therefore based on studies conducted with analogue (source) substances as part of a read across approach, which is in accordance with Regulation (EC) No. 1907/2006, Annex XI, 1.5. 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 for the analogue read-across approach is provided in the technical dossier (see IUCLID Section 13).

 

Acute toxicity: oral

CAS 67762-53-2

An acute oral toxicity study (limit test) was performed with Fatty acids, C5-9 tetraesters with pentaerythritol according to OECD guideline 420 (fixed dose procedure) (Zolyniene, 1999). 5 male and 5 female CD Sprague-Dawley rats received single oral gavage doses of 2000 mg/kg bw. No mortality occurred during the 14-day observation period. One animal had alopecia on the snout (Day 9 -15), which was not considered to be treatment-related. No further clinical signs of toxicity were reported. No effects on body weight were noted and no macroscopic findings were reported at necropsy. The acute oral LD50 value was determined to be > 2000 mg/kg bw.

 

CAS 126-57-8

The acute toxicity of Trimethylolpropane Tripelargonate was investigated following a single oral administration to the Sprague Dawley rat followed by a 14-day observation period. A first group of 3 female animals was initially dosed at 2000 mg/kg (Step 1). No mortality occurred and no clinical signs were observed. A second group of 3 female animals was then dosed at the same dose level (Step 2). No death occurred and no clinical signs were noted. Body weight changes recorded during the study were within the expected range for this strain and age of animals. No abnormalities were observed at necropsy examination performed at the end of the observation period on animals of both groups. These results indicate that the test item Trimethylolpropane Tripelargonate did not induce toxic effects in the rat following oral administration of a single dose at a level of 2000 mg/kg.

 

Acute toxicity: inhalation

CAS 67762-53-2

An acute inhalation toxicity study performed equivalent or similar to OECD TG 403 and in compliance with GLP with Carboxylic acids, C5-9, tetraesters with pentaerythritol (CAS 67762-53-2) is available (Hoffman, 1999). In this limit test groups of 10 male and 5 female CD Sprague-Dawley rats were exposed to a single dose of 5.50 mg/L air (analytical concentration) test substance aerosol for 4 h via nose/head only inhalation. Five animals of each sex were observed for 14 days after test material exposure, whereas 5 males were sacrificed on Day 3. No mortality occurred during the entire study period and clinical signs of toxicity were limited to nasal discharge recorded in all animals of the test group. The test group females lost weight during the first week after the test material exposure, but gained weight during the second week after exposure. In all other animals no effect on body weight was observed. Necropsy examination revealed no substance-related findings. Thus, the acute inhalation LC50 value was considered to be greater than 5.50 mg/L air.

 

CAS 68424-31-7

An acute inhalation toxicity study performed equivalent or similar to OECD TG 403 with Pentaerythritol tetraesters of n-decanoic, n-heptanoic, n-octanoic and n-valeric acids (CAS 68424-31-7) is available (Parr-Dobrzanski, 1994). In this limit test groups of 5 male and 5 female Alpk:APfSD rats were exposed to a single dose of 5.10 mg/L air (analytical concentration) test substance aerosol for 4 h via nose-only inhalation. The animals were observed for 14 days after administration. No mortality occurred during the entire study period and clinical signs of toxicity were limited to 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 during the study period and gross pathology revealed no abnormalities in any animal. Thus, the acute inhalation LC50 value was considered to be greater than 5.10 mg/L air.

 

Acute toxicity: dermal

CAS 71010-76-9

An acute dermal toxicity study (limit test) was performed on Decanoic acid, mixed esters with heptanoic acid, octanoic acid, pentaerythritol and valeric acid according to OECD guideline 402 and under GLP conditions (Mallory, 2006). 5 Sprague-Dawley rats/sex were exposed to 2000 mg test substance/kg bw for 24 hours under occlusive conditions. No mortality occurred. No signs of systemic toxicity were noted during the 14-day observation period. The increase in body weight was within the normal range reported for animals of this strain and this study type. No findings were reported during the macroscopic examination. The acute dermal LD50 value was found to be > 2000 mg/kg bw.

 

CAS 126-57-8

The acute toxicity of Trimethylolpropane Tripelargonate was investigated following dermal administration of a single dose to the rat. A single dose of 2000 mg/kg was administered to a group of 5 male and 5 female animals for 24 hours. After 14 days, all animals were killed and subjected to necropsy examination. No mortality occurred and no signs of toxicity were observed in male or female animals during the observation period. The body weight changes observed during the study were within the expected range for this species and age of animals. No abnormalities were found at necropsy in the animals at termination of the study, nor at the treated site. These results indicate that the test item, Trimethylolpropane Tripelargonate, has no toxic effect on the rat following dermal exposure over a 24 hour period at a level of 2000 mg/kg. The lack of mortality demonstrates the LD50 to be greater than 2000 mg/kg

 

CAS 11138-60-6

An acute dermal toxicity (limit test) was performed using Fatty acids, 8-10 (even numbered), di- and triesters with propylidynetrimethanol, according to OECD guideline 402 and under GLP conditions (Blanset, 1997). 2000 mg test substance /kg bw was applied to the skin of 5 male and 5 female New Zealand White rabbits for 24 hours under semiocclusive conditions. The observation period was 14 days. No mortality occurred and no clinical signs were observed during the 14-day observation period. 4 male animals lost 0.1 kg body weight during the observation period, while the remaining animals showed no body weight change. Necropsy at study termination revealed no abnormalities. There was no local dermal irritation at the test site. The acute dermal LD50 value in rabbits for Fatty acids, 8-10 (even numbered), di- and triesters with propylidynetrimethanol was considered to be > 2000 mg/kg bw.

 

Conclusion for acute toxicity

The reliable data available for the source substances indicate a very low level of acute toxicity following the oral, inhalation and dermal route, as LD50 and LC50 values were greater than the currently applied limit values. Therefore, as the available data did not identify any hazard for acute toxicity, Pentaerythritol, mixed esters with linear and branched fatty acids is not expected to be hazardous following acute exposure.

 

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 the source and target substance and overall quality assessment (refer to the endpoint discussion for further details).

 

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

 

Justification for classification or non-classification

According to Article 13 of Regulation (EC) No. 1907/2006 "General Requirements for Generation of Information on Intrinsic Properties of substances", information on intrinsic properties of substances may be generated by means other than tests e.g. from information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI, "General rules for adaptation of this standard testing regime set out in Annexes VII to X” 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". Since the analogue concept is applied to Pentaerythritol, mixed esters with linear and branched fatty acids, data will be generated from data for reference source substance(s) to avoid unnecessary animal testing. Additionally, once the analogue read-across concept is applied, substances will be classified and labelled on this basis.

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.