Pentaerythritol tetrastearate

Endpoint summary

Description of key information

Oral (Read-across, according to OECD 401): LD50 rat > 2000 mg/kg bw

Inhalation (Read-across, according to OECD 403): LC50 rat: >5.1 mg/L air

Dermal (Read-across, according to OECD 402): LD50 rat > 2000 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

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

Remarks:

Summary of available data used for the endpoint assessment of the target substance

Adequacy of study:

key study

Justification for type of information:

Please refer to the Analogue Approach Justification provided in Section 13.

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male/female

Dose descriptor:

LD50

Remarks:

rat

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Source: CAS 62125-22-8

The acute oral toxicity study with the analogue source substance 2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate) (CAS 62125-22-8) was selected as key result for reasons of structural similarity and data reliability. Supporting in vivo data on acute oral toxicity is given for the source substances Fatty acids, C5-10, esters with pentaerythritol (CAS 68424-31-7), Fatty acids, C8-10 mixed esters with dipentaerythritol, isooctanoic acid, pentaerythritol and tripentaerythritol (CAS 67762-53-2), and Pentanoic acid, mixed esters with PE, isopentanoic acid and isononanoic acid (CAS 146289-36-3). For all source substances the acute oral LD50 in rats was found to be >2000 mg/kg bw.

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) 1272/2008.

Executive summary:

The Read-across approach is justified in the analogue justification. The target and source substances are considered unlikely to differ in their acute toxicity potential. The acute oral LD50 in rats was found to be > 2000 mg/kg bw for the source substances 2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate) (CAS 62125-22-8), Fatty acids, C5-10, esters with pentaerythritol (CAS 68424-31-7), Fatty acids, C8-10 mixed esters with dipentaerythritol, isooctanoic acid, pentaerythritol and tripentaerythritol (CAS 67762-53-2), and Pentanoic acid, mixed esters with PE, isopentanoic acid and isononanoic acid (CAS 146289-36-3). Therefore, an acute oral LD50 value of >2000 mg/kg bw is considered for the hazard assessment and C&L purposes for the target substance Pentaerythritol tetrastearate (CAS 115-83-3).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises adequate and reliable studies (Klimisch scores 1 and 2) 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. The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) 1907/2006.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

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

Remarks:

Summary of available data used for the endpoint assessment of the target substance

Adequacy of study:

key study

Justification for type of information:

Please refer to the Analogue Approach Justification provided in Section 13.

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.1 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: Source: CAS 68424-31-7

The acute inhalation toxicity study with the analogue source substance Fatty acids, C5-10, esters with pentaerythritol (CAS 68424-31-7) was selected as key result for reasons of structural similarity and data reliability. Supporting in vivo data on acute inhalation toxicity is given for the source substance Fatty acids, C8-10 mixed esters with dipentaerythritol, isooctanoic acid, pentaerythritol and tripentaerythritol (CAS 67762-53-2). In two studies conducted similar to OECD guideline 403 the LC50 after an exposure duration of 4 hours was found to be > 4.06 mg/L air and 5.5 mg/L air in male and female rats.

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) 1272/2008.

Executive summary:

The read-across approach is justified in the analogue justification. The target and source substance are considered unlikely to differ in their acute toxicity potential. The acute inhalation LC50 was found to range from > 4.06 mg/L air (highest attainable concentration) to 5.5 mg/L air for the source substances Fatty acids, C5-10, esters with pentaerythritol (CAS 68424-31-7) and Fatty acids, C8-10 mixed esters with dipentaerythritol, isooctanoic acid, pentaerythritol and tripentaerythritol (CAS 67762-53-2). Therefore based on a weight of evidence approach, an acute LC50 value of >5 mg/L air was considered for the hazard assessment and C&L purposes for the target substance Pentaerythritol tetrastearate (115-83-3).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises adequate and reliable studies (Klimisch score 2) 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. The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) 1907/2006.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

Please refer to the Analogue Approach Justification provided in Section 13.

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Source: CAS 62125-22-8

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.

Conclusions:

The individual LD50 value determined are > 2000 mg/kg bw for male and female rats.

Executive summary:

The acute dermal toxicity of the target substance is estimated based on an adequate and reliable in vivo key study of the source substances 2,2 -bis[[(1 -oxoisooctadecyl)oxy]methyl]-1,3 -propanediyl bis(isooctadecanoate) (CAS 62125-22-8). The individual LD50 value was > 2000 mg/kg bw for male and female rats. Therefore, a LD50 value of > 2000 mg/kg bw for the target substance is considered for the hazard assessment and classification and labelling purposes. As explained in the analogue justification, the differences in molecular structure between the target and the source substances are unlikely to lead to differences in the acute dermal toxicity.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises an adequate and reliable study (Klimisch score 2) from a reference substance 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. The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) 1907/2006.

Additional information

Data on the acute toxicity of Pentaerythritol tetrastearate (CAS 115-83-3) 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) 1907/2006, Annex XI, 1.5. For each specific endpoint the source substances 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 oral toxicity

CAS 62125-22-8

The acute toxicity via the oral route of 2 2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate) (CAS 62125-22-8) has been investigated in rats in two studies. A reliable and adequate acute oral toxicity study (limit test) was performed according to OECD guideline 401 and following GLP provisions (key study, 1984). The test substance was administered by gavage at a dose of 5000 mg/kg bw to groups of five male and female rats. The animals were observed for 14 days following administration. No mortalities occurred. No clinical signs of toxicity, no changes in body weights and no differences at macroscopic examination were reported. The acute oral LD50 was therefore found to be greater than 5000 mg/kg bw.

In a second study, the acute oral toxicity was investigated in a limit test comparable to OECD guideline 401 (supporting study, 1981). The test substance was administered by gavage at a concentration of 10000 mg/kg bw (1.5 mL/100 g bw) to groups of five male and female rats. The animals were observed for 14 days following administration. No mortalities occurred. All the rats were hypoactive at the 4 h observation time point. No further signs of toxicity were noted during the study period. The acute oral LD50 was found to be greater than 10000 mg/kg bw.

CAS 68424-31-7

The study conducted with Fatty acids, C5-10, esters with pentraerythritol (CAS 68424-31-7) (supporting study,

1991) with limitations (reduced animal number), revealed no mortality and no other toxic effects, but an initial weight loss after treatment of rats with 2000 mg/kg bw. However this effect was completely reversible and the animals showed subsequently normal body weight gain. The oral LD50 value was therefore determined to exceed 2000 mg/kg bw.

CAS 67762-53-2

The acute oral toxicity of Fatty acids, C5-9 tetraesters with pentaerythritol (CAS 67762-53-2) has been investigated in two studies with rats. In the first study (supporting study, 1999), groups of 5 male and female fasted rats received single oral gavage doses of 2000 mg/kg bw. The animals were observed for 14 days following administration. No mortalities occurred. One animal showed alopecia extremities on snout which was not considered treatment related. No further clinical signs of toxicity were reported. No effect on body weight was noted. Terminal necropsy revealed no substance-related findings. Thus, the acute oral LD50 was found to be greater than 2000 mg/kg bw.

CAS 146289-36-3

A study performed according to OECD guideline 401 investigated the acute oral toxicity of Pentaerythritol ester of pentanoic acids, mixed esters with pentaerythritol, isopentanoic and isononanoic acid (CAS 146289-36-3) (supporting study, 1991). 5 male and 5 female rats were administered a single dose of 2000 mg/kg bw of the test substance by gavage. No mortality occurred during the study period. No clinical signs of toxicity were observed up to the end of the 14-day observation period and no effect on body weights was noted. Necropsy and histopathological examination revealed no substance-related findings. Therefore, the oral LD50 value in male and female rats was found to exceed 2000 mg/kg bw.

Acute inhalation toxicity

CAS 68424-31-7

An acute inhalation toxicity study was performed with Fatty acids, C5-10, esters with pentaerythritol (CAS 68424-31-7) comparable to OECD guideline 403. Five male and female rats were exposed for 4 hours to 5.0 mg/L air test substance aerosol by nose only inhalation (key study, 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.

CAS 67762-53-2

Two studies investigating the acute toxicity via the inhalation route of exposure are available for the source substance Fatty acids, C5-9 tetraesters with pentaerythritol (CAS 67762-53-2). The first study was conducted comparable to OECD Guideline 403 and according to GLP. Ten male and female rats were exposed for 4 hours to 0.48 or 4.06 mg/L test substance aerosol by whole body inhalation exposure (supporting study, 1990). No mortality, clinical signs, body weight changes or abnormalities in necropsy were observed during the 15 day study period in any group. The LC50 was therefore found to be greater than 4.06 mg/L.

CAS 67762-53-2

In the second study 10 male and 5 female rats were exposed for 4 hours to 5.5 mg/L test substance aerosol by nose/head only inhalation (supporting study, 1999). No mortalities occurred during the study period. Nasal discharge was noted as the only sign of clinical toxicity. 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 noted. Necropsy examination revealed no substance-related findings. The LC50 was therefore found to be greater than 5.50 mg/L.

Acute dermal toxicity

CAS 62125-22-8

An acute dermal toxicity test (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 under GLP conditions (key study, 1984). 5 male and 5 female rats were exposed to 2000 mg test substance / kg bw for 24 hours on the back skin under occlusive conditions. The observation period was 14 days. No mortality and 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 value in rats was found to exceed 2000 mg/kg bw.

Overall conclusion for acute toxicity

The reliable data available for the read-across analogue substances indicate a very low level of acute toxicity following exposure via the oral, inhalation and dermal route, as LD50 and LC50 values were greater than the administered limit values. Therefore, as the available data did not identify any acute toxicity, Pentaerythritol tetrastearate (CAS 115-83-3) is not considered to be hazardous following acute exposure via the oral, inhalation and dermal route.

Justification for classification or non-classification

According to Article 13 of Regulation (EC) 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 tetrastearate (CAS 115-83-3) 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 oral, inhalation and dermal toxicity do not meet the classification criteria according to Regulation (EC) 1272/2008 and are therefore conclusive but not sufficient for classification.