Registration Dossier

Administrative data

Description of key information

Oral (Read-across, OECD 407, rat) NOAEL: ≥2500 mg/kg bw/day

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
repeated dose toxicity: oral, other
Remarks:
Read across short term and subchronic oral toxicity
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, 28d
Effect level:
>= 2 500 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: absence of adverse toxic effects
Remarks on result:
other:
Remarks:
Source CAS 85883-73-4
Key result
Critical effects observed:
no

Data from the source substance Fatty acids, C6-12, esters with propylene glycol (CAS 85883-73-4) was selected as key results for reasons of structural similarity and data reliability.

Additional data from sub-chronic (90-day) oral toxicity testing is given for the source substance Decanoic acid, mixed diesters with octanoic acid and propylene glycol (CAS 68583-51-7. No adverse toxic effects were seen in this study at doses up to 1000 mg/kg bw/day. The systemic NOAEL was found to be≥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 short-term toxicity studies with structural analogue source substances. In a 28-day oral gavage study (OECD guideline 407) in male and female rats with the source substance Fatty acids, C6-12, esters with propylene glycol (CAS 85583-73-4) the NOAEL was found to be greater than 2500 mg/kg/day (highest dose tested). In a 90-day oral gavage study (OECD guideline 408) in male and female 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/day (highest dose tested). Therefore, a NOAEL for repeated dose toxicity after oral exposure of 2500 mg/kg bw/day is considered for the target substance Propylene dinonanoate (CAS 41395-83-9).
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
2 500 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 substance 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 study is 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

Read-across justification

There are no data on the repeated dose toxicity of Propylene dinonanoate (CAS 41395-83-9). 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 analogue read-across approach is provided in the technical dossier (see IUCLID Section 13).

Repeated dose toxicity, oral

CAS 85883-73-4 A 28-day sub-acute repeated oral dose toxicity study was conducted according to OECD guideline 407 under GLP conditions (key study, 2006) with Fatty acids, C6-12, esters with propylene glycol (CAS 85583-73-4). Ten rats/sex/dose were administered 0 (water control), 500, 1500, and 2500 mg/kg bw/day 7 days per week by oral gavage over 28 days. No treatment related adverse effects were observed regarding clinical signs, mortality, feed consumption, body weight, haematology, clinical chemistry, urine analysis, opthalmoscopic examination, gross pathology, organ weights and histopathology examinations. The NOAEL for sub-acute (28-day) systemic toxicity for male and female rats was 2500 mg/kg bw/day.

CAS 68583-51-7

A 90-day sub-chronic repeated oral dose 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, Propylene dinonanoate (CAS 41395-83-9) 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 Propylene dinonanoate (CAS 41395-83-9), 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.