Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Oral (Read-across, OECD 408): NOAEL sub-chronic, rat = 1000 mg/kg bw/day

The hazard assessment is based on the data currently available. New studies with the registered substance and/or other member substances of the glycol esters category will be conducted in the future. The finalised studies will be included in the technical dossier as soon as they become available and the hazard assessment will be re-evaluated accordingly.

For further details, please refer to the category concept document attached to the category object (linked under IUCLID section 0.2) showing an overview of the strategy for all substances within the glycol esters category.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
sub-chronic toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Remarks:
Summary of available data used for the endpoint assessment of the target substance
Adequacy of study:
key study
Justification for type of information:
Refer to analogue justification provided in IUCLID section 13.
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Key result
Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Remarks on result:
other: Source: CAS 151661-88-0
Key result
Critical effects observed:
no

The 90-day repeated oral dose toxicity study with the source substance Fatty acids, C18 and C18 unsatd., epoxidized, ester with ethylene glycol (CAS 151661-88-0) was selected as key result for reasons of structural similarity and data reliability. Additionally in vivo sub-chronic (90-day) oral toxicity data from a study with the source substance decanoic acid, mixed diesters with octanoic acid and propylene glycol (CAS 68583 -51 -7) resulted in an NOAEL of 1000 mg/kg bw/day in male and female rats.

Conclusions:
The read-across approach is justified in the analogue justification. The target and source substances are considered unlikely to differ in their repeated dose toxicity potential. The oral repeated dose toxicity of the target substance is estimated based on adequate and reliable sub-chronic (90 day) toxicity studies with structural analogue source substances conducted in rats. The NOAEL for sub-chronic (90 day) systemic toxicity was found to be 1000 mg/kg bw/day. Therefore, a NOAEL for repeated dose toxicity after oral exposure of 1000 mg/kg bw/day is considered for the target substance Reaction mass of 2-hydroxyethyl laurate and ethylene dilaurate (EC 908-917-6).
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
The available information comprises adequate and reliable (Klimisch score 2) studies from reference substances with a common mode of action. Read-across is justified based on different compounds having the same type of effect(s) as described in scenario 2 of the Read-Across Assessment Framework (Read-Across Assessment Framework (RAAF), European Chemicals Agency, Helsinki, Finland, 2017), (please refer to the Analogue Justification for further details provided in IUCLID section 13).The selected studies are thus sufficient to fulfil the standard information requirements set out in Annex VIII-IX, 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

Mode of Action Analysis / Human Relevance Framework

Not applicable

Additional information

The hazard assessment is based on the data currently available. New studies with the registered substance and/or other member substances of the glycol esters category will be conducted in the future. The finalised studies will be included in the technical dossier as soon as they become available and the hazard assessment will be re-evaluated accordingly.

For further details, please refer to the category concept document attached to the category object (linked under IUCLID section 0.2) showing an overview of the strategy for all substances within the glycol esters category.

Repeated dose toxicity, oral, sub-chronic

CAS 151661-88-0

A study with Fatty acids, C18 and C18 unsatd. epoxidized, ester with ethylene glycol was conducted similar to OECD guideline 408 (key study, 1991) under GLP conditions. Groups of 10 Wistar rats per sex and dose were given 100, 300 and 1000 mg/kg bw/day of the test material in peanut oil by gavage, 5 days/week for 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.

In males at 100 and 300 mg/kg bw/day a decrease of haematocrit was seen, which was considered as non-adverse effect. In males at 1000 mg/kg bw/day a decrease of erythrocytes, haemoglobin, haematocrit and lymphocytes and an increase of monocytes was seen, which was not considered as adverse effect. In females at 1000 mg/kg bw/day a decrease of white blood cells was seen, which was not considered as adverse effect. In blood of males at 1000 mg/kg bw/day an increase in protein, glucose, cholesterol, calcium and creatinine was found and in blood of males at 100 mg/kg bw/day an increase in calcium was found. These clinical chemistry findings were not considered as adverse effects.

The opthalmoscopic examinations showed no treatment- related effects. The absolute and relative organ weights in all treatment groups were comparable to the control. The macroscopic examination of the organs showed some spontaneous observations like discolouration of the thymus but no treatment -related macroscopic 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 mandibular lymph node showed effects which were due to a bacterial infection of unknown aetiology. The liver and the heart of the recovery groups (high-dose group and control group) showed the same signs of bacterial infection. The bacterial infection was judged not to affect the validity of the study. The histopathologic examination revealed no treatment -related effects.

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

 

CAS 68583-51-7

Decanoic acid, mixed diesters with octanoic acid and propylene glycol was tested for sub-chronic oral toxicity in a 90-day study performed according to OECD guideline 408 under GLP conditions (supporting study, 1993).

Groups of 10 Wistar rats per sex and dose were given 100, 300 and 1000 mg/kg bw/day of the test material in peanut oil by gavage, 5 days/week for 13 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 were included in the study to assess the reversibility of possible effects after a 34-day post-exposure recovery period. During the study period, 5 animals out of different groups died at blood collection time points, probably caused by manipulation during blood collection handling. No clinical signs or mortality occurred in relation to the test substance during the study period in any animal. No adverse effects on body weight or body weight gain were noted. Higher food consumption in the additional male high-dose group was observed due to higher body weight at start of the study. An increase in food consumption in the female high-dose group in Week 10, 12 and 13 was observed due to one animal caged individually. The water consumption of the male and female test groups showed no dose-related variations or reductions. Ophthalmoscopic examinations revealed no treatment-related findings. No treatment-related effects were noted on haematological and clinical parameters and organs weights. The macroscopic examination at autopsy and subsequent histopathological examination did not show any treatment-related changes in the mean groups or recovery groups.

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

 

Overall conclusion for repeated dose toxicity

The data for the source substances showed no toxicologically relevant effects up to and including the recommended limit values. Therefore, based on common functional groups and structural similarities, the test substance Reaction mass of 2-hydroxyethyl laurate and ethylene dilaurate is not expected to be hazardous following repeated exposure.

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 Reaction mass of 2-hydroxyethyl laurate and ethylene dilaurate 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.

The available data on repeated dose toxicity do not meet the classification criteria according to Regulation (EC) No. 1272/2008 and are therefore conclusive but not sufficient for classification.