Isooctadecanoic acid, monoester with glycerol

Endpoint summary

Description of key information

All the available subacute repeated dose toxicity studies resulted in a NOAEL ≥ 1000 mg/kg bw/day.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Analogue justification

Data on the repeated dose 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.

Repeated dose toxicity, oral, subacute

CAS No. 111-03-5

A GLP-compliant subacute oral toxicity study was performed with 2,3-dihydroxypropyl oleate at doses of 100, 300 and 1000 mg/kg bw/day, according to OECD 422 (Yamaguchi, 2005). Male and female Sprague Dawley rats (12 per sex and group, except for 1000 mg/kg bw/day: only 7 males in the main groups) received the test substance in corn oil once daily via gavage. A control group, consisting of 7 males and 12 females, was treated with the vehicle alone. The duration of treatment was 42 days (14 days prior to mating and 28 days thereafter) in males and 42-52 days (from 14 days before mating to day 4 of lactation) in females, respectively. Satellite groups for the control and 1000 mg/kg bw/day groups (5 animals per sex per group), were included to investigate the reversibility of effects during a 14-day post-exposure recovery period. No mortality occurred. No clinical signs and no neurobehavioural effects were observed during the study period. No adverse effects on body weight development were observed during the treatment and recovery period. The analysis of clinical, haematological and urinary parameters did not reveal any dose-dependent or toxicologically relevant changes in treated animals, compared with the controls. At 100 mg/kg bw/day, a significant decrease in the absolute weight of seminal vesicles in males and a significant decrease in the relative spleen weight in females were observed at necropsy. Since these effects did not follow a dose-dependent relationship and were not accompanied by any histopathological changes in the respective organs, they were not considered to be toxicologically relevant. A decrease in the relative weight of the pituitary gland in males and the thyroid in females was observed in the 1000 mg/kg bw/day satellite group. As no changes were reported for these organs in the main groups, the weight changes were not considered to be compound-related. No test substance-related changes were found at gross pathology. A low incidence of commonly found microscopic changes was evenly distributed between all groups and therefore considered to be incidental findings. One female showed a subcutaneous tumour of the mammary gland after 40 days exposure to 300 mg/kg bw/day. The benign fibroadenoma was considered to be generated naturally, as no effects were observed at the higher dose levels. Based on the overall effects observed in this subacute study, a NOAEL of 1000 mg/kg bw/day for male and female Sprague Dawley rats was derived.

CAS No. 91845-19-1

A GLP-conform study according to EU method B.7 was performed in Sprague Dawley rats with Glycerides, C16-18 and C18-hydroxy mono- and di-, at doses of 100, 500 and 1000 mg/kg bw/day (Potokar, 1985). The test substance in peanut oil or the vehicle alone was administered once daily to groups of 10 animals per sex via gavage for a period of 28 days. Satellite groups of 5 females and 5 males each were included in the 100 and 500 mg/kg bw/day groups to investigate the reversibility of effects during a 33-day post-exposure recovery period. No mortality and no clinical signs were observed during the whole study period. Following the ophthalmological examination no adverse effects were reported. The body weight gain and food consumption were comparable between the treated and control main and satellite groups. The haematology and clinical chemistry analysis did not reveal any treatment-related changes in the animals. During the macroscopic examination of the animals, no abnormal findings were observed. The histopathological examination of animals treated with 500 and 1000 mg/kg bw/day revealed non-inflammatory dilatation of lymph vessels in the small intestine as well as foreign body giant cells and vacuolization in Peyer Plaques. However, these findings were considered to be adaptive responses to the treatment, as triglycerides as resorped in the upper intestinal tract. Based on the study results, a NOAEL of ≥ 1000 mg/kg bw/day was set for male and female Sprague Dawley rats.

CAS No. 91052-13-0

The subacute oral toxicity of Glycerides, C8-18 and C18-unsatd. mono- and di-, acetates was investigated in Crl:WI (Han) rats according to OECD guideline 422 and GLP (Otterdijk, 2010). Dilutions of the test substance in polyethylene glycol were administered once daily to groups of 10 male and 5 female rats at doses of 100, 300 and 1000 mg/kg bw/day for 28 days via gavage. A control group with 10 males and 5 females received the vehicle only. In addition, satellite groups of 5 males and 5 females each for the control and high dose group were used to investigate the reversibility of any effects during a 14-day post-exposure recovery period. There were no substance-related mortalities. One female in the 1000 mg/kg bw/day group was killed in extremis on Day 17 post-coitum. Microscopic examination revealed a marked granuloma in the bronchus region containing macrophages surrounding food particles and with central areas of necrosis. These findings were indicative of a gavage accident. No substance-related clinical signs occurred during the study period. All the parameters assessed during the neurobehavioural examination were found to be normal and comparable to controls. The food consumption was similar between treated and control animals and no toxicologically relevant changes in body weights or body weight gain were noted up to and including 1000 mg/kg bw/day. Any statistically significant changes in clinical biochemistry and haematology parameters were considered to be of no toxicological relevance as these occurred in the absence of a clear treatment-related trend and remained within the range considered normal for rats of this age and strain. Any statistically significant changes in organ weights and organ to body weight ratios were considered to be of no toxicological relevance as these occurred in the absence of a clear treatment-related trend. Furthermore, the organ weight changes were within the range considered normal for rats of this age and strain and/or were present at the end of the recovery period only. At necropsy, the incidence of macroscopic and microscopic findings remained within the background range of findings that are encountered among rats of this age and strain. Since no dose-related trend was observed, these findings were considered to be of no toxicological relevance. Based on the results of this subacute toxicity study, the NOAEL for Crl:WI rats was considered to be ≥ 1000 mg/kg bw/day.

Overall conclusion for repeated dose toxicity

There are no available studies on the (sub)chronic toxicity of Glycerol monoisostearate. Therefore analogue read-across from source substances was applied.

The available data on the repeated dose oral toxicity of 3 suitable source substances are all subacute studies performed on rats. No toxicologically relevant effects were observed. In the available studies NOAEL values for repeated dose toxicity were at or above the currently applied limit dose value of 1000 mg/kg bw/day. No hazard after repeated oral exposure was identified.

Based on the available data and following the analogue approach, Glycerol monoisostearate is considered to have no long-term toxic effects via the oral route.

Justification for selection of repeated dose toxicity via oral route - systemic effects 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 repeated dose 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.