Registration Dossier

Administrative data

Description of key information

Oral: LD50 > 2000 mg/kg bw 
Inhalation: LC50 > 1.86 mg/L air (maximum attainable concentration of respirable particles)
Dermal: 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, 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 (Klimisch score 2 due to read-across) study 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 (refer to the 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 adverse effect observed
Quality of whole database:
The available information comprises an adequate, reliable (Klimisch score 2 due to read-across) study 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 (refer to the 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.

Additional information

Analogue justification

Data on the acute inhalation and dermal toxicity of 1,2,3-propanetriyl triisooctadecanoate (CAS No. 26942-95-0) are not available. The assessment was therefore based on studies conducted with analogue 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) and within Chapter 5.1 of the CSR.

Acute oral toxicity

CAS No. 26942-95-0

An acute oral toxicity study with 1,2,3-propanetriyl triisooctadecanoate was performed in Sprague Dawley CFY rats according to OECD guideline 401 and under GLP-conditions (Jones, 1987). The test substance was administered via gavage to 5 rats/sex at the limit dose of 2000 mg/kg bw. No mortality occurred during the study period and no signs of toxicity were noted up to the end of the 14-day observation period. No effect on body weight was noted and gross pathology did not reveal any abnormal findings related to treatment. Under the conditions of this study, the oral LD50 value for male and female Sprague Dawley CFY rats is considered to be > 2000 mg/kg bw.

In an acute oral toxicity study performed according to OECD guideline 401 and in compliance with GLP, 1,2,3-propanetriyl triisooctadecanoate was administered via gavage to groups of 5 Sprague-Dawley rats per sex at the limit dose of 2000 mg/kg bw (Saboureau, 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 Sprague Dawley rats is > 2000 mg/kg bw.

In an acute oral toxicity study performed similar to OECD guideline 401, 5 female Swiss mice were administered 2000 mg/kg bw 1,2,3-propanetriyl triisooctadecanoate by gavage (Bouffechoux, 1996). The study report contained limited data. The summary indicated that no mortality occurred during the 14-day observation period; no clinical signs were noted in the animals; the increase in body weight was within the expected range for this species and strain; and no treatment-related findings were reported during necropsy. Therefore, the oral LD50 value for female Swiss mice is > 2000 mg/kg bw.

 

Acute inhalation toxicity

CAS No. 73398-61-5

The acute inhalation toxicity of Triglycerides, mixed decanoyl and octanoyl was studied in rats according to OECD guideline 403 and in compliance with GLP (Reminghaus, 1976). Agroup of 10 male rats was exposed to a calculated concentration of 28.1 µL/L air for 6 h using a nose-only exposure system. The measured respirable test substance concentration was 1.97 µl/L (particles with a diameter below 10 µm), corresponding to an atmosphere concentration of the test aerosol of 1.86 mg/L. This was considered to be the maximum attainable concentration of respirable particles. 10 male control animals were sham-exposed. No mortality and no clinical signs of toxicity were observed in any of the animals during exposure, nor during the 14-day observation period. Body weight gain was not affected during the study. At necropsy, no abnormalities were noted. Microscopic examination did not reveal any abnormal findings in lungs or tracheae and no deposits of the oily test substance in the respiratory tissues were detected. Based on these results, the LC50 value for male rats is > 1.86 mg/L.

Acute dermal toxicity

CAS No. 555-43-1

In an acute dermal toxicity study, Glycerol tristearate was investigated in rats in accordance with OECD guideline 402 and in compliance with GLP (Krueger, 1998). Five rats/sex were dermally exposed to the test substance at a limit dose of 2000 mg/kg bw. The powdery test substance was suspended in corn oil at a concentration of 40 g/100 m³ and applied to the shaved skin of the test animals (5 cm³/kg bw) for 24 h under semi-occlusive conditions. After the exposure period, residual test substance was removed and the animals were observed for a period of 14 days. No treatment-related mortalities occurred and no signs of systemic toxicity were observed during the study. Male rats showed the expected gain in body weight throughout the study. Minimal body weight gain was recorded in 2/5 females, whereas 1/5 females showed no gain in body weight. However, this finding was not considered to be toxicologically relevant, as no other adverse effects were observed. During necropsy, macroscopic examination revealed no test substance-related abnormalities. Based on these results, the dermal LD50 value for male and female rats is > 2000 mg/kg bw.

Overall conclusion for acute toxicity

The acute oral toxicity of the target substance 1,2,3-propanetriyl triisooctadecanoate was assessed in 3 studies in the rat and the mouse. No mortality was observed, leading to an overall acute oral LD50 > 2000 mg/kg bw. No toxicologically relevant signs of systemic toxicity were reported.

Inhalation is not a relevant route of exposure for 1,2,3-propanetriyl triisooctadecanoate, given the very low vapour pressure. Exposure to aerosols, particles or droplets of inhalable size cannot be excluded for formulated products intended for use in spraying applications. An acute inhalation study with the source substance Triglycerides, mixed decanoyl and octanoyl (CAS No. 73398-61-5) resulted in an acute inhalation LC50 > 1.86 mg/L (maximum attainable concentration of respirable particles) and no toxic effects.

The source substance Glycerol tristearate (CAS No. 555-43-1) was tested for its potential for acute dermal toxicity. No mortality occurred, resulting in an acute dermal LD50 value > 2000 mg/kg bw. No toxicologically relevant signs of systemic toxicity were reported.

Based on the available data on the target and sources substances, and following the analogue approach, 1,2,3-propanetriyl triisooctadecanoate is considered to be not toxic after acute exposure by the oral, inhalation and dermal routes.


Justification for selection of acute toxicity – oral endpoint
The selected study is the most adequate and reliable study with the lowest dose descriptor.

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 most 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 a structural analogue. The selected study is most 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 1,2,3-propanetriyl triisooctadecanoate (CAS No. 26942-95-0), 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 toxicity do not meet the classification criteria according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.