Isooctadecanoic acid, 1,1'-(2,2-dimethyl-1,3-propanediyl) ester

Endpoint summary

Description of key information

Oral (OECD 423): LD50 >5000 mg/kg bw 
Inhalation (OECD 436): LC50 >5.22 mg/L
Dermal: Waiving

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 an adequate and reliable study, and is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, 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 an adequate, reliable study (Klimisch score 2 due to read-across) from a reference substance with similar structure and intrinsic properties. Read-across is justified based on similar functional groups and similar precursors/breakdown products (refer to endpoint discussion for further details). 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) No 1907/2006.

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Justification for read-across

There are no data available for the acute inhalation toxicity of isooctadecanoic acid, 1,1'-(2,2-dimethyl-1,3-propanediyl) ester (CAS 109884-54-0). In accordance with Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met.” In particular for human toxicity, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from structurally related substances (grouping or read-across).

Having regard to the general rules for the read-across approach laid down in Annex XI, Item 1.5, of Regulation (EC) No 1907/2006 whereby substances may be predicted as similar provided that their physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a comparable pattern as a result of structural similarity, the substance heptanoic acid, ester with 2,2-dimethyl-1,3-propanediol (CAS 68855-18-5) is selected as source substance.

 

Acute toxicity: oral

CAS 109884-54-0

A key acute oral toxicity study performed with isooctadecanoic acid, 1,1'-(2,2-dimethyl-1,3-propanediyl) ester (CAS 109884-54-0) according to OECD TG 423 and in compliance with GLP is available (Latour, 2014a). In this study following the acute toxic class method two groups of three female fasted Wistar rats were administered a single dose of 2000 mg/kg bw of the test substance in a stepwise procedure via oral gavage. The animals were observed for 15 days after administration. No mortalities were observed during the study period but clinical signs such as hunched posture and/or piloerection were noted for all animals on Days 1 and/or 2. The body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain. No abnormalities were found at macroscopic post mortem examination of the animals. The acute oral LD50 value for females was considered to be greater than 2000 mg/kg bw. Moreover, in accordance with OECD TG 423, the oral LD50 cut-off of the test substance may be considered to be >5000 mg/kg bw.

Acute toxicity: inhalation

CAS 68855-18-5

An acute inhalation toxicity study was performed with Heptanoic acid, ester with 2,2-dimethyl-1,3-propanediol (CAS 68855-18-5) according to OECD guideline 436 (acute toxic class method) and under GLP conditions. Three RccHanTM:WIST rats/sex were exposed for 4 h to 5.22 mg/L (mean achieved concentration) test substance aerosol by nose only inhalation (Griffiths, 2012). The test concentration was chosen based on the outcome of a preliminary test with two rats at a dose of 2.14 mg/L. No mortality occurred throughout the study period. Signs of hunched posture and piloerection were commonly seen in animals for a short period after removal from the exposure chamber following exposure. Wet fur was commonly recorded both during and for a short period after exposure. These observations were considered to be associated with the restraint procedure and, in isolation, were not indicative of toxicity. In addition, an increased respiratory rate was noted in all animals. On removal from the chamber and 1 h post-exposure, all animals exhibited increased respiratory rate and ataxia. One day after exposure, all animals still showed increased respiratory rate, hunched posture as well as occasional instances of piloerection. All animals recovered to appear normal from Days 5 to 8 post-exposure. All animals showed the expected body weight gain during the study, except for one female that did not gain weight during the final week of the 14-day observation period. In addition, one male exhibited a slight loss in body weight on the first day of exposure. Necropsy revealed no treatment-related findings. The detailed macroscopic examination of the respiratory tract did not reveal signs of irritancy or local toxicity. The inhalation LC50 value in rats was determined to be > 5.22 mg/L.

 

Conclusion for acute toxicity

The reliable data available for the target and source substance indicate a very low level of acute toxicity following the oral and inhalation route, as LD50 and LC50 values were greater than the currently applied limit values. The dermal absorption rate for the target substance was predicted to be very low (see IUCLID section 7.1), thus, the dermal uptake can be expected to be negligible. In conclusion, as the available data did not identify any hazard for acute toxicity, isooctadecanoic acid, 1,1'-(2,2-dimethyl-1,3-propanediyl) ester is not considered to be hazardous following acute exposure. 

Justification for selection of acute toxicity – oral endpoint
The reliable GLP compliant OECD Guideline study was choosen.

Justification for selection of acute toxicity – inhalation endpoint
Hazard assessment is conducted by means of read-across from a structural analogue. The selected study is the most adequate and reliable study based on the identified similarities in structure and intrinsic properties between 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 isooctadecanoic acid, 1,1'-(2,2-dimethyl-1,3-propanediyl) ester, 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.