Tetraesters of pentaerythritol with 2-ethylhexanoic acid and heptanoic acid and nonanoic acid

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 Tetraesters of pentaerythritol with 2-ethylhexanoic acid, heptanoic acid and nonanoic acid (EC 806-879-4) 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 71010-76-9

An acute oral toxicity study with Decanoic acid, mixed esters with heptanoic acid, octanoic acid, pentaerythritol and valeric acid (CAS 71010-76-9) was performed according to OECD guideline 425 (up and down procedure, limit test) and according to GLP (Mallory, 2006). A total of 5 female Sprague-Dawley rats were administered 2000 mg/kg bw. No mortality occurred, and no clinical signs of toxicity were observed during the 14-day observation period. The body weight gain was within the range that is normal for this animal strain and study type. No findings were reported during the macroscopic examination. The acute oral LD50 value in female rats was considered to be > 2000 mg/kg bw.

CAS 78-16-0

An acute oral study was performed according to EU Method B.1 (limit test) and under GLP conditions using 2-ethyl-2-[[(1-oxoheptyl)oxy]methyl]propane -1,3-diyl bisheptanoate (Reijnders, 1987). Only limited information about the test substance was reported. The test substance was administered by gavage to male and female Wistar rats. In a pilot study one animal per sex was administered 1800, 3200 and 5000 mg/kg bw. In the main study five males and females received 5000 mg/kg bw. No mortality occurred during the 14-day observation period. There were no treatment-related clinical signs and no effects on body weight were noted. No findings were reported during the macroscopic examination. The acute oral LD50 value in rats was > 5000 mg/kg bw.

CAS 68424-31-7

The potential acute oral toxicity of Fatty acids, C5-10, esters with pentraerythritol was assessed in a study conducted following a protocol similar to OECD guideline 401 (Robinson, 1991). 2 rats/sex/dose were administered 2000 mg/kg bw by gavage. There was no mortality during the study period. The male rats showed slight toxicity, but no details were reported. An initial weigh loss was ascribed to the pre-dosing fasting period and the rats gained weight during the study period. The gross pathological examination did not show substance-related findings. The acute oral LD50 value was considered to be > 2000 mg/kg bw.

Acute toxicity: inhalation

RA from CAS 67762-53-2

The acute toxicity via inhalation of Fatty acids, C5-9 tetraesters with pentaerythritol was investigated in a study performed according to OECD guideline 403 and under GLP conditions (Hoffman, 1999). 10 male and 5 female CD Sprague-Dawley rats were exposed for 4 hours to 5.5 mg/L (analytical concentration) aerosol by nose/head only inhalation. A control group with 10 rats/sex/dose were exposed to air only. No mortality occurred during the study period. Nasal discharge was noted as the only sign of clinical toxicity. The treatment females lost weight during the first week after exposure, but gained weight during the second week. No effect on body weight was noted in the treated males or control group. The gross pathology and histopathological examination did not show substance-related findings. The LC50 value was therefore considered to be > 5.50 mg/L (analytical concentration).

CAS 68424-31-7

An acute inhalation toxicity study was performed with Pentaerythritol tetraesters of n-decanoic, n-heptanoic, n-octanoic and n-valeric acids, similar to OECD guideline 403 (Parr-Dobrzanski, 1994). 5 Alpk:APfSD rats/sex were exposed for 4 hours to 5.10 mg/L test substance aerosol by nose only inhalation (analytical concentration). The test substance caused no mortality during the 15 day study period. The animals exhibited a hunched position, chromodacryorrhea, piloerection, staining around the nose and wet fur. These signs occurred during or just after the exposure and were clearly consistent with the use of restraints. The body weight gain was within the range that is normal for this animal strain and study type. No findings were reported during the macroscopic examination. The LC50 value was therefore found to be > 5.1 mg/L (analytical concentration).

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 78-16-0

The acute dermal toxicity of 2-ethyl-2-[[(1-oxoheptyl)oxy]methyl]propane -1,3-diyl bisheptanoate was assessed in a study conducted similar to the “16 CFR 1500.40” guideline (Morgareidge, 1974). The study report contained limited documentation. to 2000 mg test substance/kg bw was applied to the skin of 10 albino rabbits (5 with intact and 5 with abraded skin) for 24 hours. The type of coverage was not reported. No mortality occurred and no clinical signs were observed during the 14-day observation period. Therefore, the LD50 value was found to be > 2000 mg/kg bw.

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, Tetraesters of pentaerythritol with 2-ethylhexanoic acid, heptanoic acid and nonanoic acid (EC 806-879-4) 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 Tetraesters of pentaerythritol with 2-ethylhexanoic acid, heptanoic acid and nonanoic acid (EC 806-879-4), data will be generated from information on 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.