Fatty acids C18-C22 (even numbered), tetraesters with pentaerythritol

Endpoint summary

Description of key information

Oral: LD50 m/f rat > 2000 mg/kg bw

Read-across from structural analogue source substance 2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate) (CAS 62125-22-8, key)

 

Inhalation: LC50 m/f rat > 5.5 mg/L

Read-across from structural analogue source substance fatty acids, C5-9 tetraesters with pentaerythritol (CAS 67762-53-2, key)

 

Dermal: LD50 m/f rat > 2000 mg/kg bw

Read-across from structural analogue source substance 2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate) (CAS 62125-22-8, key)

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:

refer to analogue justification provided in IUCLID 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

Reason / purpose for cross-reference:

read-across source

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, 1984, RL1

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), decanoic acid, mixed esters with heptanoic acid, octanoic acid, pentaerythritol and valeric acid (CAS 71010-76-9), pentaerytritol tetraoleate (CAS 19321-40-5) 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) No. 1272/2008

Conclusions:

The available data on suitable source substances did not show any toxic effects. Therefore, the target substance fatty acids C18-C22 (even numbered), tetraesters with pentaerythritol is not considered to be hazardous following acute exposure via the oral route.

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:

refer to analogue justification provided in IUCLID 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:

> 5.5 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: Source: CAS 67762-53-2, 1999, RL2

Further acute inhalation toxicity studies as supporting information with the source substances fatty acids, C5-9 tetraesters with pentaerythritol (CAS 67762-53-2) and fatty acids, C5-10, esters with pentaerythritol (CAS 68424-31-7) were available. In both studies, no mortality was observed and the LC50 values were found to be > 4.06 and > 5.1 mg/L air after 4 h of exposure (aerosol), respectively.

Interpretation of results:

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

Conclusions:

The available data on suitable source substances did not show any toxic effects. Therefore, the target substance fatty acids C18-C22 (even numbered), tetraesters with pentaerythritol is not considered to be hazardous following acute exposure by inhalation.

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 dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

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:

refer to analogue justification provided in IUCLID section 13

Reason / purpose for cross-reference:

read-across source

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, 1984, RL2

A further acute dermal toxicity study as supporting information is available with the source substance decanoic acid, mixed esters with heptanoic acid, octanoic acid, pentaerythritol and valeric acid (CAS 71010-76-9), which resulted in a LD50 > 2000 mg/kg bw.

Interpretation of results:

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

Conclusions:

The available data on suitable source substances did not show any toxic effects. Therefore, the target substance fatty acids C18-C22 (even numbered), tetraesters with pentaerythritol is not considered to be hazardous following acute exposure via the dermal route.

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.

Additional information

Justification for read-across

Data on acute oral, inhalation and dermal toxicity of fatty acids C18-C22 (even numbered), tetraesters with pentaerythritol are not available. The assessment of acute oral, inahaltion and dermal 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 oral toxicity

CAS 62125-22-8

2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate) (CAS 62125-22-8) was administered by gavage at a concentration of 5000 mg/kg bw to groups of five male and female Wistar rats according to OECD 401 and GLP (Notox, 1984). 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 found to be greater than 5000 mg/kg bw.

In a second study similar to OECD 401 2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate) (CAS 62125-22-8) was administered by gavage at a concentration of 10000 mg/kg bw to five female and male Wistar rats, respectively (Toxicol Laboratories, 1981). All the rats were hypoactive at the 4 h observation period. However, no further signs of toxicity were noted and no mortality occurred during the study period. The acute oral LD50 was found to be greater than 10000 mg/kg bw.

CAS 19321-40-5

Pentaerytritol tetraoleate (CAS 19321-40-5) was tested in an acute oral toxicity test conducted according to OECD 423 and GLP (Notox, 1997). A single dose of 2000 mg of the test substance per kg bw was administered to three male and female Wistar rats. 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 found to be greater than 2000 mg/kg bw.

CAS 68424-31-7

Fatty acids, C5-10, esters with pentaerythritol (CAS 68424-31-7) was tested at a dose level of 2000 mg/kg bw following oral administration in male and female albino rats similar to OECD 401 (ICI Central Toxicological Laboratory, 1991). Mortality was not observed and the oral LD50 value was found to be > 2000 mg/kg bw.

CAS 146289-36-3

Pentanoic acid, mixed esters with PE, isopentanoic acid and isononanoic acid (CAS 146289-36-3) was tested in an acute oral toxicity test conducted according to OECD 401 and GLP. 2000 mg of the test substance per kg bw was administered to three male and female Wistar rats (Henkel, 1991). 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 found to be greater than 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 425 (up and down procedure, limit test) and GLP (Calvert Laboratories, 2006). Decanoic acid, mixed esters with heptanoic acid, octanoic acid, pentaerythritol and valeric acid was administered by gavage to one female Sprague-Dawley rat at the starting dose of 2000 mg/kg bw. Since no mortality and no other toxic effects could be detected during the 14 day study period, 4 further female animals were equally dosed with 2000 mg/kg bw. No clinical signs of toxicity and no mortality were observed up to the end of the 14-day observation period. No effect on body weight was noted. Finally, necropsy revealed no substance-related findings. The oral LD50 value in female rats was found to exceed 2000 mg/kg bw.

CAS 67762-53-2

An acute oral toxicity study (limit test) was performed via the oral route of fatty acids, C5-9 tetraesters with pentaerythritol (CAS 67762-53-2) according to OECD 420 (fixed dose procedure) (Huntington Life Science, 1999). Groups of 5 males and females fasted CD Sprague-Dawley 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. Finally necropsy revealed no substance-related findings. Thus, the acute oral LD50 was found to be greater than 2000 mg/kg bw.

 

Acute inhalation toxicity

CAS 67762-53-2

The acute toxicity via the inhalation route of fatty acids, C5-9 tetraesters with pentaerythritol (CAS 67762-53-2) has been investigated in rats in two studies, which were conducted comparable to OECD 403 under GLP conditions.

In the key study 10 male and 5 female CD Sprague-Dawley rats were exposed for 4 hours to 5.5 mg/L test substance aerosol by nose/head only inhalation (Huntington Life Sciences, 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, the highest attainable dose with respect to testing.

In the supporting study 10 male and female Sprague-Dawley rats were exposed for 4 hours to 0.48 or 4.06 mg/L test substance aerosol by whole body inhalation exposure (MEHSL, 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 68424-31-7

An acute inhalation toxicity study was performed with fatty acids, C5-10, esters with pentraerythritol (CAS 68424-31-7) comparable to OECD 403 (Zeneca Central Toxicology Laboratory, 1994). 5 male and female Alpk:APfSD rats were exposed for 4 hours to 5.0 mg/L test substance aerosol by nose only inhalation. 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.

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 402 and GLP (Notox, 1984). 5 male and female Wistar rats each 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 in rats 2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate) was found to exceed 2000 mg/kg bw.

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 (CAS 71010-76-9) comparable to OECD 402 and GLP (Calvert Laboratories, 2006). 5 male and female Sprague-Dawley rats were exposed to 2000 mg test substance /kg bodyweight for 24 hours on the back skin under semiocclusive conditions. The observation period was 14 days. No clinical signs of systemic toxicity and no mortality 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 in rats for Decanoic acid, mixed esters with heptanoic acid, octanoic acid, pentaerythritol and valeric acid was found to exceed 2000 mg/kg bw.

 

Overall conclusion for acute toxicity

The reliable data available from analogue source substances considered for read-across indicate a very low level of acute toxicity following the oral, inhalation and dermal route. Therefore, the target substance fatty acids C18-C22 (even numbered), tetraesters with pentaerythritol 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) 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 fatty acids C18-C22 (even numbered), tetraesters with pentaerythritol 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.