Fatty acids, tall-oil, esters with ethylene glycol

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, embryotoxicity/teratogenicity ≥ 900 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

Key result

Dose descriptor:

NOAEL

Remarks:

maternal systemic toxicity rat

Effect level:

900 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 91031-31-1

Key result

Abnormalities:

no effects observed

Key result

Dose descriptor:

NOAEL

Remarks:

embryotoxicity/teratogenicity rat

Effect level:

900 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: Source: CAS 91031-31-1

Key result

Abnormalities:

no effects observed

Key result

Developmental effects observed:

no

Data from the source substance Fatty acids, C16-18, esters with ethylene glycol (CAS 91031-31-1) was selected as key results for reasons of structural similarity and data reliability. Additional data from the source substance Decanoic acid, mixed diesters with octanoic acid and propylene glycol (CAS 68583-51-7) is given. In a study conducted according to OECD guideline 414 the NOAEL for maternal systemic toxicity and the NOAEL for embryotoxicity/teratogenicity was found to be 1000 mg/kg bw/day.

Conclusions:

The read-across approach is justified in the analogue justification. The target and source substance are considered unlikely to differ in their reproduction toxicity potential. Developmental toxicity data was provided for two structural analogue source substances, Fatty acids, C16-18, esters with ethylene glycol (CAS 91031-31-1) and Decanoic acid, mixed diesters with octanoic acid and propylene glycol (CAS 68583-51-7). Both source substances were tested according to OECD guideline 414 in rats. In both studies the highest tested dose of 1000 mg/kg bw/day and 900 mg/kg bw/day were found to be the resulting developmental NOAEL. No relevant hazard with regard to developmental toxicity is therefore identified for the target substance and NOAEL values for maternal and developmental toxicity of ≥ 900 mg/kg bw/day are used for the target substance Fatty acids, tall-oil, esters with ethylene glycol (CAS 68187-85-9) in terms of hazard assessment and C&L.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

900 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 91031-31-1

A prenatal developmental toxicity GLP study (key 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 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. Mortality was recorded twice daily and the dams were observed for clinical signs 2 times per day. The Body weight was recorded on GD 0, 6, 16, and 20 and necropsy with macroscopic examinations was performed on GD 20 following sacrifice. The ovaries and uterine content was examined for gravid uterus weight, number of corpora luteae, number of implantations, number of early resorptions and number of late resorptions. The number of live foetuses and sex ratio was recorded. An external examination was performed on all foetuses while soft tissue examinations, skeletal examinations, and head examinations were performed in half of the offspring in each litter.

No maternal systemic toxicity was observed and no treatment-related effects on maternal reproductive parameters were noted, leading to a NOAEL for maternal developmental toxicity in rats of 900 mg/kg bw/day. Based on a lack of treatment-related effects in the foetal parameters the NOAEL for developmental toxicity/teratogenicity was 900 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. Mortality was recorded twice daily and the dams were observed for clinical signs 2 times per day. The body weight was recorded on GD 0, 6, 16, and 20 and necropsy with macroscopic examinations was performed on GD 20. The ovaries and uterine content was examined for gravid uterus weight, number of corpora luteae, number of implantations, number of early resorptions and number of late resorptions. The number of live foetuses and sex ratio was recorded. An external examination was performed on all foetuses while soft tissue examinations, skeletal examinations, and head examinations were performed in half of the offspring in each litter. Based on the absence of adverse effects on maternal toxicity and maternal developmental toxicity the NOAEL for maternal systemic and developmental toxicity in rats was 1000 mg/kg bw/day.

The skeletal and visceral malformations observed in the examined foetuses were found in similar numbers and severity the control and treatment groups and were considered to be incidental. The NOAEL for developmental toxicity/teratogenicity 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 ≥ 900 mg/kg bw/day (the highest dose tested) and no hazard for reproduction (development) was identified. Based on the available data and following the analogue approach, no hazard for reproduction (development) was identified for the target substance Fatty acids, tall-oil, esters with ethylene glycol (68187-85-9).

Mode of Action Analysis / Human Relevance Framework

Not applicable.

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". By applying the analogue concept to Fatty acids, tall-oil, esters with ethylene glycol (68187-85-9), data will be generated from 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 reproduction toxicity do not indicate a hazard for reproduction toxicity.