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

Endpoint summary

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

Effects on developmental toxicity

Description of key information

Oral (read across, OECD 414, rat): NOAEL maternal systemic ≥ 1000 mg/kg bw/day

Oral (read across, OECD 414, rat): NOAEL development ≥ 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.

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

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: no adverse effects observed

Remarks on result:

other: Source CAS 85883-73-4

Key result

Abnormalities:

no effects observed

Key result

Dose descriptor:

NOAEL

Remarks:

embryotoxicity/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: no adverse effects observed

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 propylene glycol monocaprylate (CAS 85883-73-4) were selected as key results for reasons of structural similarity and data reliability.

Additional developmental toxicity data were available for the source substance Decanoic acids, mixed diesters with octanoic acid and propylenglycol (CAS 68583-51-7) and Fatty acids, C16-18; ester with ethylenglycol (CAS 91031-31-1). Both substances were tested according to OECD guideline 414 in rats. In both studies the highest tested dose 1000 mg/kg bw/day and 900 mg/kg bw/day were found to be the resulting developmental NOAEL.

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 three developmental toxicity studies in rats with a) Fatty acids, C6-12, esters with propylene glycol (CAS 85883-73-4), b) Decanoic acid, mixed esters with octanoic acid and propylene glycol (CAS 68583-51-7), and c) Fatty acids, C16-18, esters with ethylene glycol (CAS 91031-31-1) no developmental effects were observed. The NOAELS were greater than the highest doses tested (≥900 mg/kg/day). Therefore no developmental toxicity is expected for target substance isooctadecanoic acid, monoester with propane-1,2-diol (CAS 68171-38-0).

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, eco-toxicological 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, 8.7, 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

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.

 

Developmental toxicity/ teratogenicity

CAS 85883-73-4

A prenatal developmental toxicity GLP study (key study, 2007) was performed according to OECD guideline 414 with propylene glycol monocaprylate (CAS 85883-73-4). 25 female Sprague-Dawley rats/dose were dosed once daily by oral gavage during gestational days 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 was examined for gravid uterus weight, number of corpora lutea, number of implantations, number of early resorptions and number of late resorptions. Fetal examinations comprised external examinations, soft tissue examinations, skeletal examinations, and head examinations.

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

CAS 91031-31-1

A prenatal developmental toxicity GLP study (supporting study, 1997) was performed according to OECD guideline 414 with Fatty acids, C16-18; ester with ethylene glycol (CAS 91031-31-1). 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 900 mg/kg bw/day of the test substance in 0.5% sodium carboxymethylcellulose and 0.25% Cremophor in aqua dest. as vehicle. Maternal examinations comprised twice daily cage side observations and clinical observations, body weight on GD 0, 6, 16, and 20 and necropsy with macroscopic examinations on GD 20. The ovaries and uterine content was 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 toxicity, maternal developmental toxicity and foetuses the NOAEL for developmental toxicity/teratogenicity and for maternal developmental toxicity in rats was ≥ 900 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 the limit dose of 1000 mg/kg bw/day. Based on the available data and following the analogue approach, absence of adverse effects on fertility is expected for the target substance Isooctadecanoic acid, monoester with propane-1,2 -diol (CAS 68171 -38 -0).

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. 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 meet the classification criteria according to Regulation (EC) 1272/2008 and are therefore conclusive but not sufficient for classification.