Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Link to relevant study records
Reference
Endpoint:
screening for reproductive / developmental toxicity
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because a pre-natal developmental toxicity study is available
Reason / purpose for cross-reference:
data waiving: supporting information
Effect on fertility: via oral route
Endpoint conclusion:
no study available
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available

Effects on developmental toxicity

Description of key information

Developmental toxicity/teratogenicity and maternal toxicity (Read-across, OECD 414) NOAEL rat: ≥2500 mg/kg bw/day

Link to relevant study records
Reference
Endpoint:
developmental 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:
maternal toxicity rat
Effect level:
>= 2 500 mg/kg bw/day (actual dose received)
Based on:
test mat.
Basis for effect level:
other: NOAEL corresponding to the highest dose tested
Remarks on result:
other: Source CAS 85883-73-4
Key result
Abnormalities:
no effects observed
Key result
Dose descriptor:
NOAEL
Remarks:
developmental toxicity / teratogenicity rat
Effect level:
>= 2 500 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: NOAEL corresponding to the highest dose tested
Remarks on result:
other:
Remarks:
Source: CAS 85883-73-4
Key result
Abnormalities:
no effects observed
Key result
Developmental 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 a developmental toxicity study 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 NOAEL for maternal and developmental/teratogenicity 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 developmental toxicity potential.
In a developmental toxicity oral gavage study (OECD 414) in rats with the analogue substance Fatty acids, C6-12, esters with propylene glycol (CAS 85883-73-4) the NOAEL for developmental toxicity/teratogenicity and maternal toxicity was found to be greater than 2500 mg/kg/day (highest dose tested).
In a developmental toxicity oral gavage study (OECD 414) in rats with the analogue substance Decanoic acid, mixed diesters with octanoic acid and propylene glycol (CAS 68583-51-7) the NOAEL for developmental toxicity/teratogenicity and maternal toxicity was found to be greater than 1000 mg/kg/day (highest dose tested).
Therefore, no hazard with regard to developmental toxicity / teratogenicity is expected for the target substance Propylene dinonanoate (41395-83-9).
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subacute
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 VIIII-IX, 8.7, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

Read-across justification

There are no data on the reproduction toxicity of Propylene dinonanoate (CAS 41395-83-9). The assessment was therefore based on repeated dose toxicity 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).

Developmental toxicity/ teratogenicity

CAS 85883-73-4

A pre-natal developmental toxicity GLP study (key study, 2007) was performed according to OECD guideline 414 with Fatty acids, C6-12, esters with propylene glycol (CAS 85883-73-4). 25 female Sprague-Dawley rats/dose were dosed once daily by oral gavage during gestational days (GD) 6-17 with 0 (water control), 500, 1500 and 2500 mg/kg bw/day of the neat test substance. Maternal examinations comprised twice daily cage side observations, daily clinical observations, body weight and feed consumption on GD 0, 6-18 (daily), and 20 and necropsy with macroscopic examinations on GD 20. The ovaries and uterine content were examined for gravid uterus weight, number of corpora lutea, number of implantations, number of early resorptions and number of late resorptions. Foetal examinations comprised external examinations, soft tissue examinations, skeletal examinations, and head examinations.

Based on the absence of adverse effects on maternal and developmental toxicity the NOAEL for developmental toxicity/teratogenicity and for maternal toxicity in rats was ≥ 2500 mg/kg bw/day.

CAS 68583-51-7

A prenatal developmental toxicity GLP study (supporting study, 1994) was performed according to OECD guideline 414 with Decanoic acids, mixed diesters with octanoic acid and propylenglycol (CAS 68583-51-7). 24 female Sprague-Dawley rats/dose were dosed once daily by oral gavage during gestational days 6-15 with 0 (vehicle control), 100, 300 and 1000 mg/kg bw/day of the test substance in arachis oil. Maternal examinations comprised twice daily clinical observations, body weight determination on GD 0, 6, 16, and 20 and necropsy with macroscopic examinations on GD 20. The ovaries and uterine content were examined for gravid uterus weight, number of corpora lutea, number of implantations, number of early resorptions and number of late resorptions. Foetal examinations comprised external examinations, soft tissue examinations, skeletal examinations, and head examinations.

Based on the absence of adverse effects on maternal and developmental toxicity, the NOAEL for developmental toxicity/teratogenicity and for maternal toxicity in rats was ≥1000 mg/kg bw/day.

Overall conclusion for developmental toxicity/teratogenicity

Analogue read-across from source substances was applied for the developmental toxicity /teratogenicity endpoint. No effects on reproductive parameters/organs were observed in the available prenatal developmental toxicity studies. The NOAEL for developmental toxicity was at 2500 mg/kg bw/day. Based on the available data and following the analogue approach, absence of adverse effects on developmental toxicity/teratogenicity is expected for the target substance Propylene dinonanoate (CAS 41395-83-9)

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. Based on the analogue read-across approach, the available data on toxicity to reproduction does not meet the classification criteria according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and is therefore conclusive but not sufficient for classification.

Therefore, based on the analogue read-across approach, the available data on reproduction toxicity do not indicate a hazard for reproduction toxicity.

Additional information