Isooctadecanoic acid, monoester with glycerol

Endpoint summary

Description of key information

The available acute oral toxicity study performed with the target substance Glycerol monoisostearate resulted in an acute oral LD50 > 2000 mg/kg bw. 
The available acute dermal toxicity study performed with 2 source substances resulted in an acute dermal LD50 > 2000 mg/kg bw. 
The available acute inhalation toxicity study performed with a source substance resulted in an acute inhalation LC50 > 1.86 mg/L air (maximum attainable concentration of respirable particles).

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

Analogue justification

Data on the acute inhalation and dermal toxicity of Glycerol monoisostearate (CAS 66085-00-5) 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 grouping of chemicals and read-across is provided in the technical dossier (see IUCLID Section 13) and within Chapter 5.1 of the CSR.

Acute oral toxicity

CAS No. 66085-00 -5

In an acute oral toxicity study performed according to OECD guideline 401 and in compliance with GLP, Glycerol monoisostearate was administered via gavage to groups of 5 Sprague Dawley rats per sex at a limit dose of 2000 mg/kg bw (Saboureau, 1989). No mortalities and no clinical signs were observed in the animals up to the end of the 14-day observation 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.

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). A group 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. 91845-19-1

The acute dermal toxicity of Glycerides, C16-18 and C18-hydroxy mono- and di- was tested in accordance with EU method B.3 and in compliance with GLP (Potokar, 1985). The study was performed as a limit test in rats (5 males and 5 females) at a dose level of 2000 mg/kg bw. The test substance was applied unchanged to the clipped skin of the test animals for 24 h under occlusive conditions. After removal of the test substance, animals were observed for a period of 14 days. No mortalities and no local dermal effects were noted during the course of the study. No clinical signs of toxicity were observed. The body weight gain was within the normal range in males and females during the whole study period. Necropsy and histopathological examination revealed no substance-related findings. One (1) male and 2 female animals showed a reddening of the ileum mucosa, which was not considered to be treatment-related. Based on these results, the dermal LD50 value for male and female rats is > 2000 mg/kg bw.

CAS No. 91052-13-0

The acute dermal toxicity of Glycerides, C8-18 and C18-unsatd. mono- and di-, acetates was investigated in a limit test according to OECD guideline 402 and in compliance with GLP (Otterdijk, 2010). In this study, 5 male and 5 female rats were treated with the test substance at a dose of 2000 mg/kg bw. The test substance was dissolved in polyethylene glycol at a concentration of 200 mg/mL and applied onto the shaved skin of the test animals (10 mL/kg bw) for 24 h under occlusive conditions. After exposure, residual test substance was removed and animals were observed for a period of 14 days. No mortalities occurred and body weight gain of all animals was within the normal range during the whole study period. Flat posture was noted in all animals on Day 1. On the same day, chromodacryorrhoea was observed in 3/5 males and in 2/5 females. Ptosis was seen in 2/5 males and in 4/5 females, and 3/5 females showed restless behaviour on Day 1. Scales and scabs of the right flank and/or treated skin were observed among 3/5 males and 1/5 females between Days 4 and 15. At necropsy, no substance-related findings were noted. Therefore, the LD50 in male and female rats is > 2000 mg/kg bw.

Overall conclusion for acute toxicity

The acute oral toxicity of the target substance Glycerol monoisostearate was assessed in a study in which no mortality was observed, leading to an 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 Glycerol monoisostearate, 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.

Two source substances were tested for acute dermal toxicity. No mortality occurred in any of the available studies, resulting in acute dermal LD50 values > 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, Glycerol monoisostearate is considered to be not toxic after acute exposure by the oral, inhalation and dermal routes.

Justification for selection of acute toxicity – oral endpoint
There is only one study available.

Justification for selection of acute toxicity – inhalation endpoint
There is only one study available.

Justification for selection of acute toxicity – dermal endpoint
No study was selected, as a Weight of Evidence approach was applied.

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 Glycerol monoisostearate (CAS No. 66085-00-5), 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 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.