Isooctadecanoic acid, monoester with propane-1,2-diol

Endpoint summary

Description of key information

Oral (read across, OECD 408, rat) NOAEL: ≥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

Remarks:

rat, 90d

Effect level:

7 355 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

female

Basis for effect level:

other: absence of adverse toxic effects

Remarks on result:

other:

Remarks:

Source: CAS 1323-39-3

Key result

Dose descriptor:

NOAEL

Remarks:

rat, 90d

Effect level:

5 657 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male

Basis for effect level:

other: absence of adverse toxic effects

Remarks on result:

other:

Remarks:

Source: CAS 1323-39-3

Key result

Critical effects observed:

no

Data from the source substance Propylene glycol monostearate (CAS 1323-39-3) were selected as key results for reasons of structural similarity and data reliability.

Additional oral repeated dose toxicity data were available for the source substance Decanoic acids, mixed diesters with octanoic acid and propylenglycol (CAS 68583-51-7): In a 90-day (subchronic) oral toxicity study conducted according to OECD guideline 408 , the NOAEL for systemic toxicity for male and female Wistar rats was found to be the highest tested dose of 1000 mg/kg bw/day.

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. In a sub-chronic (90-day) oral repeated dose studies in rats with the source substance stearic acid, monoester with propane-1,2-diol / 2-hydroxypropyl stearate (CAS 1323-39-3) the NOAEL was found to be greater than 5000 mg/kg bw/day. In a sub-chronic (90-day) oral repeated dose studies in rats with the source substance Decanoic acids, mixed diesters with octanoic acid and propylene glycol (CAS 68583-51-7) the NOAEL was found to be greater than 1000 mg/kg bw/day. Therefore no systemic repeated dose toxicity is expected for target substance isooctadecanoic acid, monoester with propane-1,2-diol (CAS 68171-38-0).

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 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 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

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, subacute

CAS 1323-39-3

A repeated dose 90-day oral toxicity study was performed similar to OECD guideline 408 (key study, 1967) with Propylene glycol monostearate (CAS 1323-39-3). 24 rats/sex/dose were administered 1.5, 3.36, and 7.52% of test substance nominal in diet (w/w). As calculated from the reported mean body weights and feed consumption the highest dose was equivalent to 5657 mg/kg bw/day for male and 7355 mg/kg bw/day for female rats. The treatment period was 13 weeks.

Rats were observed daily for clinical abnormalities, body weights and feed consumption were measured weekly, water consumption was measured daily, haematology and clinical chemistry were assessed in week 1 and 13, urine was collected during week 1 and 12, gross pathology, histopathology and organ weights were determined after sacrifice at study termination. All of the 192 test animals survived until termination of the study and were sacrificed. A very high incidence of demonstrable lung involvement was observed upon necropsy. 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. Limited, scattered incidental gross findings were observed in groups of rats, male and female, fed the control or the test material diets. The incidence of such findings in the control rats as well as the rats on the test diets in this experiment negated any significance to a dose related response in the experimental animals. All effects were of minor clinical relevance and found to be non-adverse, and therefore of no toxicological relevance. Based on the absence of adverse toxic effects, the NOAEL for subchronic (90-day) systemic toxicity for male and female Sprague Dawley rats was greater than 5000 mg/kg bw/day.

 

CAS 68583-51-7

A repeated dose 90-day oral toxicity study was conducted according to OECD guideline 408 and under GLP conditions (supporting study, 1993) with Decanoic acids, mixed diesters with octanoic acid and propylene glycol (CAS 68583-51-7). 10 rats/sex/dose and 5 satellite control and high dose rats/sex were administered 0 (vehicle control), 100, 300, 1000 mg/kg bw/day 5 days per week by oral gavage over 90 days.

Rats were observed daily for clinical abnormalities. The body weight, and feed and water consumption were measured weekly; while haematology and clinical chemistry were assessed in week 6 and week 13. Opthalmoscopic examination, gross pathology, histopathology examinations were performed, and organ weights were determined after sacrifice at study termination. One female at 100 mg/kg bw/day died at the last investigation and blood collection; one male at 300 mg/kg bw/day died in week 7 at the intermediate investigation and blood collection and 1 female at 300 mg/kg bw/day died at the last investigation and blood collection. 1 female and 1 male at 1000 mg/kg bw/day died at the last investigation and blood collection. No substance-related mortality was observed and no toxicologically relevant effects were observed. Based on the absence of adverse toxic effects, the NOAEL for sub-chronic (90-day) systemic toxicity for male and female Wistar rats was 1000 mg/kg bw/day.

 

Overall conclusion for repeated dose toxicity

The data for the read-across analogue substance showed that no effects were observed up to and including the recommended limit values. Therefore, as the available data did not identify any hazard for repeated dose toxicity, Isooctadecanoic acid, monoester with propane-1,2-diol (CAS 68171-38-0) is not considered 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 Isooctadecanoic acid, monoester with propane-1,2-diol (CAS 68171-38-0), 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 repeated dose toxicity do not meet the classification criteria according to Regulation (EC) 1272/2008 and are therefore conclusive but not sufficient for classification.