Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

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
Additional information

No study is available investigating the toxicity to reproduction of Propanediol dicaprylate (CAS 56519-71-2).

In accordance with Regulation (EC) No 1907/2006, Annex VIII, 8.7.1., column 1, a Screening study for reproductive/developmental toxicity, one species (OECD 421 or 422) is required “if there is no evidence from available information on structurally related substances, from (Q)SAR estimates or from in vitro methods that the substance may be a developmental toxicant.”

In accordance with Regulation (EC) No 1907/2006, Annex VIII, 8.7.1., column 2 “this study does not need to be conducted if a pre-natal developmental toxicity study (Annex IX, 8.7.2) or a two-generation reproductive toxicity study (Annex IX, Section 8.7.3) is available.”

A pre-natal developmental toxicity study (Annex IX, 8.7.2) is available which was conducted with the structurally related source substance Decanoic acid, mixed diesters with octanoic acid and propylene glycol (CAS 68583-51-7) via the oral route, according to OECD guideline 414.

The results of the study showed that a repeated oral administration (days 6-15 post coitum) of the test material to pregnant rats caused no symptoms of cumulative toxicity up to a dose level of 1000 mg/kg bw/d. The test material was not cumulative toxic to pregnant rats and did not reveal any embryotoxic or teratogenic potential. Furthermore, there were no treatment-related effects in reproduction at dose levels up to 1000 mg/kg bw/d.

As a consequence, according to Regulation (EC) No 1907/2006, Annex VIII, 8.7.1., column 2, another Screening study for reproductive/developmental toxicity, one species (OECD 421 or 422) does not need to be conducted.

Additionally, there is one study available investigating the repeated dose toxicity from the source substance Decanoic acid, mixed diesters with octanoic acid and propylene glycol (CAS 68583-51-7). Based on the results of the histopathological analysis of the sexual organs (no adverse effects on reproductive organs were observed in a 90-day repeated dose toxicity study), the substance is unlikely to have any effect on the reproductive performance.


Short description of key information:
There is no study available.

Effects on developmental toxicity

Description of key information
NOAEL (P, F1) ≥1000 mg/kg bw/d (OECD 414)
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 an adequate and reliable study (Klimisch score 2) from a reference substance with similar structure and intrinsic properties. Read-across is justified based on common functional group(s), common precursors and breakdown products and similarities in PC/ECO/TOX properties (refer to endpoint discussion for further details). The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VIII-IX, 8.7, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.
Additional information

Justification for grouping of substances and read-across

There are no data available on the developmental toxicity of Propanediol dicaprylate (CAS 56519-71-2). In order to fulfill the standard information requirements set out in Annex VIII, 8.7, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from a structurally related substance was conducted.

In accordance with 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).

Having regard to the general rules for grouping of substances and read-across approach laid down in Annex XI, Item 1.5, of Regulation (EC) No 1907/2006 whereby substances may be predicted as similar provided that their physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity.

Overview of developmental toxicity

CAS

Chemical name

Molecular weight

Developmental toxicity

56519-71-2

Propanediol dicaprylate

328.49

RA: CAS 68583-51-7

68583-51-7

Decanoic acid, mixed diesters with octanoic acid and propylene glycol

328.49 - 384.59

Experimental result:
NOAEL (P, F1) ≥1000 mg/kg bw/day (OECD 414)

The above mentioned substances are considered to be similar on the basis of the structural similar properties and/or activities. The available endpoint information is used to predict the same endpoint for Propanediol dicaprylate (CAS 56519-71-2). A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

A developmental toxicity study is available which was conducted with the source substance Decanoic acid, mixed diesters with octanoic acid and propylene glycol (CAS 68583-51-7) in accordance with OECD guideline 414 and under GLP conditions to assess the effects on embryonic and fetal development in pregnant CD rats. The substance was tested at dose levels of 0 (control), 100, 300 and 1000 mg/kg bw/d. Each group consisted of 24 female rats. The test material was administered orally by gavage once daily from days 6 to 15 of gestation. A standard test volume of 5 mL/kg bw was used. Control animals were dosed with the vehicle alone (arachidis oil, DAB 10) over the period described. Clinical signs of toxicity and any reaction to treatment were recorded at least once daily. Body weights were recorded at days 0, 6, 16 and 20 of gestation. All surviving animals were sacrificed on day 20 of gestation and the fetuses were removed by cesarean section. At necropsy, the females were examined macroscopically and live fetuses were weighed, sexed and examined for visceral and skeletal abnormalities. The dams tolerated the applied doses up to 1000 mg/kg bw/d without lethality. No substance related symptoms were observed in all treatment groups. Maternal body weight gain was not affected by treatment. No treatment-related abnormalities were found at necropsy in all females. Apart from the control group (6 dead fetuses), all animals had viable fetuses. Pre- and post implantation loss, embryonic deaths, mean numbers of resorptions and total fetuses were not affected by treatment. Mean fetal placental and uterus weight were not affected by treatment. Fetal sex ratio was comparable in all groups. No treatment-related fetal abnormalities were found at necropsy. There were no treatment-related effects in reproduction. The examined fetuses showed no treatment-related malformations. The figures of skeletal variations in both the test groups and the control group were considered to be similar. For skeletal ossification some deviations were identified in the test groups 100 and 1000 mg/kg bw/d, respectively. They were noted as no treatment-related effects and considered to be within the normal range. Visceral variations in both the test groups and the controls were considered to be similar. The results of the study showed that a repeated oral administration (days 6-15 post coitum) of the test material to pregnant rats caused no symptoms of cumulative toxicity up to a dose level of 1000 mg/kg bw/d. According to the study described, the test material is not cumulative toxic to pregnant rats and does not reveal any embryotoxic or teratogenic potential at dose levels up to 1000 mg/kg bw/d.

Supportive information :

Expected metabolites of propanediol dicaprylate are octanoic acid and 1,3-propanediol. Octanoic acid is a short-chain fatty acid and as such part of the daily diet. It has the status of 'generally regarded as safe' (GRAS) in the US and is listed as a direct additive to food (US Code of Federal Regulations, 21(3), 21CFR184.1025).

A teratogenicity study was performed on 1,3-propanediol according to OECD guideline 414 and the principles of GLP (Leuschner, 1992). In this study, female rats were treated by oral gavage with 250 or 1000 mg/kg bw from day 6 to day 15 of gestation. All animals survived the treatment, and 250 mg/kg bw was identified as the no-observed effect level. At 1000 mg/kg bw, a slight decrease in body weight gain was noted. No findings in regard to pre-natal developmental toxicity were observed.

Thus, no toxicity for reproduction is expected for the likely metabolites of propanediol dicaprylate.


Justification for selection of Effect on developmental toxicity: via oral route:
Hazard assessment is conducted by means of read-across from a structural analogue. The selected study is the most adequate and reliable study based on the identified similarities in structure and intrinsic properties between source and target substance and overall assessment of quality, duration and dose descriptor level (refer to the endpoint discussion for further details).

Justification for classification or non-classification

Based on read-across from a structurally related substance and following an analogue approach, the available data on the toxicity to reproduction and the developmental toxicity do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC and are therefore conclusive but not sufficient for classification.