Fatty acids, C16-18, stearyl esters

Endpoint summary

Description of key information

Oral (read across, similar to OECD 401): LD50 m/f rat > 5000 mg/kg bw

Inhalation (read across, OECD 436): LC50 m/f rat: >5.7 mg/L air

Dermal (read across, OECD 402): LD50 m/f 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:

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

Key result

Sex:

male/female

Dose descriptor:

LD50

Remarks:

rat

Effect level:

> 20 mL/kg bw

Based on:

test mat.

Remarks:

corresponding to 17400 mg/kg bw based on a relative density of 0.87 g/cm³

Remarks on result:

other: Source: CAS 90990-29-7

The acute oral toxicity study with the source substance Fatty acids, C16 and C18-22 - unsatd., C16-18 and C18 unsatd. alkyl ester (CAS 90990-29-7) was selected as key result for reasons of structural similarity and data reliability. Additional in vivo data on acute oral toxicity in rats and mice were available for the three source substance Hexadecanoic acid, -isooctadecyl ester (CAS 72576-80-8) and 2-octyldodecyl myristate (CAS 22766-83-2) and decyl oleate (CAS 3687-46-5). For all substances the acute oral LD50 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 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 was found to be ≥2000 mg/kg bw for the analogue source substances Fatty acids, C16 and C18-22 - unsatd., C16-18 and C18 unsatd. alkyl ester (CAS 90990-29-7), Hexadecanoic acid, -isooctadecyl ester (CAS 72576-80-8), 2-octyldodecyl myristate (CAS 22766-83-2) and decyl oleate (CAS 3687-46-5). Therefore, an acute oral LD50 value of >2000 mg/kg bw was considered for the hazard assessment and C&L purposes for the target substance Fatty acids, C16-18 (even numbered), stearyl esters (CAS 85536-04-5).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises adequate and reliable studies (Klimisch scores ≤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 studies are thus sufficient to fulfil the standard information requirements set out in Annex VIII-IX, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 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)

Adequacy of study:

key study

Justification for type of information:

Refer to the Analogue Approach Justification document provided in Section 13.

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male/female

Dose descriptor:

LC50

Remarks:

rat

Effect level:

> 5.7 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: No mortality occurred. Apart from hunched position observed in all rats on day 2 after exposure, no further signs of adverse toxicity were observed during the 14-day observation period.

Interpretation of results:

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

Conclusions:

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 be > 5.7 mg/L air for the source substance 2-ethylhexyl oleate (CAS 26399-02-0). Therefore, an acute LC50 value of >5 mg/L air was considered for the hazard assessment and C&L purposes for the target substance Fatty acids, C16-18 (even numbered), stearyl esters (CAS 85536-04-5).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises an adequate and reliable study (Klimisch scores 1). The selected studies are 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

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

Remarks:

rat

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Source: CAS 93803-87-3

In vivo acute dermal toxicity data from the source substance 2-octyldodecyl isooctadecanoate (CAS 93803-87-3) was selected as key result for reasons of structural similarity and data reliability. Additional in vivo acute dermal toxicity data was available for the source substance decyl oleate (CAS 3687-46-5), for which an acute dermal LD50 value of >2000 mg/kg bw was found in male and female rats.

Interpretation of results:

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

Conclusions:

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 dermal LD50 was found to be ≥2000 mg/kg bw for the analogue source substance 2-octyldodecyl isooctadecanoate (CAS 93803-87-3) and decyl oleate (CAS 3687-46-5). Therefore, an acute dermal LD50 value of 2000 mg/kg bw was considered for the hazard assessment and C&L purposes for the target substance Fatty acids, C16-18 (even numbered), stearyl esters (CAS 85536-04-5).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises adequate and reliable studies (Klimisch scores ≤2). The selected studies are 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 read-across

Data on the acute toxicity of Fatty acids, C16-18 (even numbered), stearyl esters (CAS 85536-04-5) 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 oral toxicity

CAS 90990-29-7

The potential acute oral toxicity of Fatty acids, C16 and C18-22 - unsatd., C16-18 and C18 unsatd. alkyl ester (CAS 90990-29-7) was assessed in a study performed according to a protocol similar to OECD 401 (key study, 1982). 5 rats/sex were administered 20 mL/kg bw (corresponding 17400 mg/kg bw based on a relative density of 0.87 g/cm³) of the test substance by gavage. No mortality occurred. No clinical signs were observed during the 14-day observation period and no effect on body weight was noted. No unusual findings were reported during the macroscopic examination. Based on the results of the conducted study, the oral LD50 value is considered to be > 20 mL/kg bw (corresponding to 17400 mg/kg bw based on a relative density of 0.87 g/cm³).

CAS 72576-80-8

The potential acute oral toxicity of Hexadecanoic acid, -isooctadecyl ester (CAS 72575-80-8) was assessed in a study performed according to OECD 401 (supporting study, 1999). 5 rats/sex were administered 2000 mg/kg bw of the test substance by gavage. No mortality occurred. No clinical signs were observed during the 14-day observation period and the body weights were comparable between the control group and treatment group. A gross pathology examination was not performed. Based on the results of the conducted study, the oral LD50 is considered to be > 2000 mg/kg bw.

CAS 22766-83-2

In an acute oral toxicity study performed according to OECD guideline 401 and in compliance with GLP, 29.75 g 2-octyldodecyl myristate/kg bw was administered via gavage to 5 OFA.Sprague-Dawley (IOPS Caw) rats/sex (supporting study, 1989). No mortality occurred during the 14-day observation period. No clinical signs were observed in the animals during the study period. The increase in body weight was within the normal range reported for animals of this strain. Gross pathology did not reveal any substance-related findings in the treated animals. Therefore, the oral LD50 value for male and female rats is > 29.75 g/kg bw.

CAS 3687-46-5

In a non-guideline acute oral toxicity study, 5 female mice were administered 2000 mg/kg bw decyl oleate via the oral route (supporting study, 1994). The study report contained limited information on animal husbandry and no individual animal data. The summary indicated that no mortality occurred during the 6-day observation period, and that no clinical signs were noted in the animals. There were no effects on body weight. Therefore, the oral LD50 value for female mice is > 2000 mg/kg bw.

Acute inhalation toxicity

CAS 26399-02-0

The acute inhalation toxicity of 2-ethylhexyl oleate (CAS 26399-02-0) was assessed in a study performed according to OECD guideline 436 (key study, 2010). 3 rats/sex were administered 5.7 ± 0.4 mg/L (actual concentration) of the test substance as an aerosol via nose-only exposure for 4 h. The nominal concentration was 15.4 mg/L and the MMAD was 2.5-2.6 µm. No mortality occurred. The animals had a hunched posture on Day 2; no further clinical signs were observed during the 14-day observation period. The body weight gain was within the range that is normal for this strain and study type. No findings were reported during the macroscopic examination. The inhalation LC50 value is considered to be > 5.7 mg/L.

Acute dermal toxicity

CAS 93803-87-3

The dermal effects of 2-octyldodecyl isooctadecanoate were investigated in an acute dermal toxicity GLP study performed similar to OECD guideline 402 (key study, 1998). In a limit test 2000 mg/kg bw of the undiluted test substance was applied to the shaved skin of 5 rats/sex for 24 h under occlusive conditions. After the exposure period, residual test substance was removed and the animals were observed for a period of 14 days. No mortality occurred. Red staining of the fur was observed in 1/5 females on Day 8 – 13. As this is a known sign of stress in rats, it was not considered to be a toxicologically relevant effect. Male and female rats showed the expected gain in body weight throughout the study. The necropsy and histopathological examination did not reveal any substance-related findings. Based on these results, the dermal LD50 value for male and female rats is > 2000 mg/kg bw.

CAS 3687-46-5

An acute dermal toxicity study (limit test) was performed with decyl oleate (CAS 3687-46-5) according to OECD guideline 402 (supporting study, 2010). 2000 mg/kg bw of the test substance was applied to the skin of 5 Wistar rats/sex under an occlusive dressing for 24 hours. No mortality occurred. Clinical signs were observed in all males on Day 1 and/or 2; as piloerection (2/5 males) or chromodacryorrhoea (3/5 males). No clinical signs were noted in females. The body weight increases were within the range expected for rats used in this type of study and no treatment-related findings were reported during the necropsy and histopathological examination. Erythema (grade 1) was observed on the treated skin for up to 4 days during Day 3-7 in 4/5 females. Scales or scabs (grade 1) were noted on the treated skin area in 5/5 females and 3/5 males for up to 9 days during Day 7-15 of the observation period. The LD50 is considered to be > 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 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, Fatty acids, C16-18 (even numbered), stearyl esters (CAS 85536-04-5) 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, C16-18 (even numbered), stearyl esters (CAS 85536-04-5), 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.