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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

Oral (OECD 408): 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
Quality of whole database:
The available information comprises adequate, reliable (Klimisch score 2 ) studies from reference substances with similar structure and intrinsic properties. Read-across is justified based on common functional group(s), common precursors/breakdown products and similarities in PC/ECO/TOX properties (refer to endpoint discussion for further details).
Taken together, the information from these independent sources is consistent and provides sufficient weight of evidence for hazard assessment leading to an endpoint conclusion in accordance with Annex XI, 1.2, of Regulation (EC) No 1907/2006. Therefore, the available information as a whole is sufficient to fulfil the standard information requirements set out in Annex VIII, 8.6, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

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

Justification for read-across

There are no data for repeated dose toxicity available for Fatty acids, C16-18, 2-hydroxyethyl esters (CAS 97281-23-7). In accordance with Regulation (EC) No 1907/2006, Annex XI, 1.5 read-across from appropriate substances is conducted to fulfill the standard information requirements set out in Regulation (EC) No 1907/2006, Annex VIII, 8.6.

According to 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) “to avoid the need to test every substance for every endpoint”.

  

Fatty acids, C16-18, 2-hydroxyethyl esters is an UVCB substance comprised of mainly mono- and diesters of ethylene glycol conjugated with C16 and C18 fatty acids. Thus, the test substance represents a glycol ester, which in general is known to be stepwise hydrolysed by gastrointestinal enzymes into the free fatty acid components and the respective alcohol (Long, 1958; Lehninger, 1970; Mattson and Volpenhein, 1972). Considering the common metabolism, the read-across approach is based on the presence of common precursors and the likelihood of common breakdown products via biological processes that result in structurally similar chemicals, and on common functional groups, structural similarities and similar physico-chemical, toxicological and toxicokinetic behaviour. For further details on the read-across approach, please refer to the analogue justification in section 13 of the technical dossier.

 

As no reliable data are available on repeated dose toxicity, read-across to the analogue substances Propylene glycol monostearate (CAS 1323-39-3) and Fatty acids, C18 and C18 unsatd. epoxidized, ester with ethylene glycol (CAS 151661-88-0) was conducted.

 

CAS 1323-39-3

Propylene glycol monostearate was tested in a subchronic study via the oral route following a protocol similar to OECD guideline 408 (Saatman, 1967). Stearic acid, monoester with propane-1,2-diol was administered to groups of 24 Sprague-Dawley rats per sex and dose at 1.5, 3.36 and 7.52% in the diet (calculated doses: 1158, 2571 and 5657 mg/kg bw/day (males) and 1461, 3214 and 7355 mg/kg bw/day (females)) for a period of 90 days. Furthermore, a group receiving an isocaloric control diet containing 7.52% mono-and diglycerides was included as control group. In all treatment groups, the total fat additive in the diet was equal to 7.52% by substitution with a control fat mono-and diglycerides.

No mortality occurred during the study period in any animal. A mild respiratory infection of the pleuro-pneumonia-like organism type was present in the weanling rats when they were assigned to the diets but the majority of the animals showed no observable signs of infection after the first few weeks on test. No significant difference in growth rate was observed in females. The mean body weight of male rats fed 1.5% of the test substance in the diet was significantly higher during Week 6 and 7. No effects on food efficiency were observed. A non-adverse increase in water consumption was seen in different groups during the study period without a dose-relationship. Blood chemical analyses, haematological determinations and urine analysis showed no finding in incidence or concentration considered to be substance-related. When organ to body weight or brain weight ratios for each experimental group of rats were compared separately with the control group, no biologically relevant differences were observed. During gross pathology, a very high incidence of demonstrable lung involvement was observed upon necropsy of the rats in this study. 163/192 rats showed gross lung pathology. These findings, mainly diffuse congestion and consolidation, were not related to any diet or sex but reflected a general condition of the entire group of rats. Histopathology revealed no substance-related adverse effects.

Based on the lack of adverse effects, a NOAEL of 7.52 % in the diet equivalent to the calculated doses of 7355 mg/kg bw/day (f) and 5657 mg/kg bw/day (m) was identified in this study.

 

CAS 151661-88-0

Repeated dose toxicity of Fatty acids, C18 and C18 unsatd. epoxidized, ester with ethylene glycol was tested similar to OECD guideline 408 and under GLP criteria (Pittermann, 1991). Groups of 10 rats per sex and dose were given 100, 300 and 1000 mg test substance/kg bw/day solved in peanut oil by gavage, 5 days/week for ca. 13.5 weeks. A concurrent negative control group receiving the vehicle only was included. Furthermore, additional satellite control and high-dose groups with 5 animals per sex and dose were included in the study for a 32-33-day recovery period. No mortality or clinical signs of toxicity occurred during the study period. The total body weight gain of all groups showed no deviation and was comparable to the control group. The mean food and water consumption in all treated groups was comparable to the control group. Relative and absolute organ weights showed no substance-related differences to the control group.

Haematological parameters showed few and slight differences to the control values and were considered incidental The biochemical examinations revealed dose-independent findings which were not considered to be substance-related. The opthalmoscopic examinations showed no compound-related effects. The absolute and relative organ weights in all groups showed no deviations and were comparable to the control. The macroscopical examination of the organs displayed some spontaneous observations like discolouration of the thymus but no compound-related macroscopical effects were observed. However, in the male and female animals of all groups (including the recovery and control groups) the livers, the heart and the mandibulary lymph node showed effects which were due to a bacteriosis of unknown etiology. The liver and the heart of the recovery groups (high-dose group and control group) showed the same signs of bacteriosis and therefore prove the persistence of the bacteriosis. The histopathologic examination revealed no compound-related effects.

Based on the lack of adverse effects, a NOAEL of 1000 mg/kg bw/day (m, f) was identified in this study.

 

Conclusion on repeated dose toxicity

The available data show that the analogue substances Propylene glycol monostearate (CAS 1323-39-3) and Fatty acids, C18 and C18 unsatd. epoxidized, ester with ethylene glycol (CAS 151661-88-0) do not possess intrinsic hazardous properties in regard to repeated dose toxicity. Therefore, based on common functional groups and structural similarities, the target substance Fatty acids, C16-18, 2-hydroxyethyl esters (CAS 97281-23-7) is considered to be non-hazardous after short- and long-term exposure.

 

References

A detailed reference list is provided in the technical dossier (see IUCLID, section 13) and within the CSR.


Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Hazard assessment is conducted by means of read-across from structural analogues. All available studies are adequate and reliable based on the identified similarities in structure and intrinsic properties between source and target substances and overall quality assessment (refer to the endpoint discussion for further details).

Justification for classification or non-classification

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, and are therefore conclusive but not sufficient for classification.