Fatty acids, C16-18, stearyl esters

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

Oral (OECD 422, read across): NOAEL rat, fertility≥1000 mg/kg bw/day

Oral (OECD 422, read across): NOAEL rat, systemic toxicity≥1000 mg/kg bw/day

Link to relevant study records

Reference

Endpoint:

screening for reproductive / 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 the 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:

reproduction

Effect level:

>= 1 000 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No adverse effects observed in the study

Remarks on result:

other:

Remarks:

Source: CAS 22393-85-7

Key result

Critical effects observed:

no

Key result

Dose descriptor:

NOAEL

Remarks:

developmental

Generation:

F1

Effect level:

>= 1 000 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No adverse effects observed in the study

Remarks on result:

other:

Remarks:

Source: CAS 22393-85-7

Key result

Critical effects observed:

no

Critical effects observed:

no

Reproductive effects observed:

no

A combined repeated dose toxicity study with reproduction/developmental toxicity study with the source substance tetradecyl oleate (CAS 22393-85-7) was selected as key result for reasons of structural similarity and data reliability.

Additionally, a combined repeated dose toxicity study with reproduction/developmental toxicity study with the source substance Docosyl docosanoate (CAS 17671-27-1) is given. Rats were administered with doses up to 1000 mg/kg bw/day via gavage. Males were exposed for 28-29 days, from two weeks before mating on test day one until after mating. Females were exposed for 54 days (during 2 weeks prior to mating, during mating, during post-coitum, and during 3 days of lactation). Based on the absence of toxicologically relevant effects, both the NOAEL for parental fertility and the developmental NOAEL for offspring was ≥1000 mg/kg bw/day.

Conclusions:

The read across approach is justified in the analogue justification. The target and source substances are considered unlikely to differ in their reproduction toxicity potential. Combined repeated dose toxicity studies with reproduction/developmental toxicity screening were performed with the two source substances Tetradecyl oleate (CAS 22393-85-7) and Docosyl docosanoate (CAS 17671-27-1) via the oral route of administration. In both studies the NOAEL for parental fertility and the developmental NOAEL was found to be ≥1000 mg/kg bw/day. Therefore, no hazard with regard to reproduction toxicity is expected for target substance Fatty acids, C16-18 (even numbered), stearyl esters (CAS 85536-04-5).

Effect on fertility: 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 1) 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. 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 fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

There are no data on the reproduction toxicity of the target substance Fatty acids, C16-18 (even numbered), stearyl esters (CAS 85536-04-5). The assessment was therefore based on studies conducted with analogue source 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).

Toxicity to reproduction

CAS 22393-85-7

A combined repeated dose toxicity study with a reproduction/developmental toxicity screening test was performed according to OECD Guideline 422 under GLP conditions (key study, 2014). 10 rats/sex/dose were administered 0, 100, 300 and 1000 mg/kg bw/day Tetradecyl oleate (CAS 22393-85-7) once daily, via oral gavage. Males were exposed for 28-29 days, from two weeks before mating on test day one until after mating. Females were exposed for 54 days (during 2 weeks prior to mating, during mating, during post-coitum, and during 3 days of lactation).

No treatment-related parental effects were seen on viability, clinical signs, body weight (gain), food consumption, haematological parameters, clinical chemistry parameters, during observational and neurological screening, and during macroscopic and microscopic examinations. Therefore the NOAEL for parental systemic toxicity was ≥ 1000 mg/kg bw/day.

In parental animals, no effects on reproductive function (qualitative sperm staging, oestrus cycle) or performance (male and female mating and fertility indices, conception index, pre-coital interval, and number of corpora luteae and implantation sites, gestation length) were observed, compared with the control animals. The testis weight, epididymis weight, and histological examination of the testes in males as well as the weight and histological examination of the uterus and ovaries in females did not reveal any substance-related effects in the parental animals. All the pregnant females gave birth to live pups with the exception of one high dose female which had a total litter loss on day 3 post-partum. This female and two females in the control group had unilateral implantation, which is not considered to be treatment-related.

Therefore, a NOAEL for parental fertility of≥ 1000 mg/kg bw/day was derived for male and female rats.

 

CAS 17671-27-1

A combined repeated dose toxicity study with a reproduction/developmental toxicity screening test was performed according to OECD guideline 422 under GLP conditions (supporting study, 2014). 10 rats/ sex/dose were administered 0, 100, 300 and 1000 mg/kg bw/day Docosyl docosanoate once daily, via gavage. Males were exposed for 28-29 days, from two weeks before mating on test day one until after mating. Females were exposed for 54 days (during 2 weeks prior to mating, during mating, during post-coitum, and during 3 days of lactation).

No treatment-related parental effects were seen on viability, clinical signs, body weight (gain), food consumption, clinical chemistry parameters, during observational screening, and during macroscopic and microscopic examinations. In females, an increase in bilirubin, cholesterol and triglyceride levels was recorded at 300 and 1000 mg/kg. As this was only observed in one sex and no other hepatic changes were observed, this is not considered to be toxicologically relevant. Lower locomotor activity was recorded in males at 100 mg/kg and in females at 300 and 1000 mg/kg. As no effects were noted on other neurological parameters, this is not considered to be toxicologically relevant. Therefore, the NOAEL for parental systemic toxicity was ≥ 1000 mg/kg bw/day.

In parental animals, no effects on reproductive function (qualitative sperm staging, oestrus cycle) or performance (male and female mating and fertility indices, conception index, precoital interval, and number of corpora lutea and implantation sites, gestation length) were observed, compared with the control animals. One female from the control group had a 100% postimplantation loss, which is considered to be incidental. The testis weight, epididymis weight, and histological examination of the testes in males as well as the weight and histological examination of the uterus and ovaries in females did not reveal any substance-related effects in the parental animals. Therefore, a NOAEL for parental fertility of ≥1000 mg/kg bw/day was derived for male and female rats.

 

Overall conclusion for effects on fertility

Analogue read-across from source substances was applied for reproduction toxicity. No effects on reproductive parameters/organs were observed in the available screening study. The NOAEL for reproduction 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 can be anticipated for the target substance Fatty acids, C16-18 (even numbered), stearyl esters (CAS 85536-04-5).

Effects on developmental toxicity

Description of key information

Oral (OECD 422, read across): NOAEL rat, developmental≥ 1000 mg/kg bw/day

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 1) 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. 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

There are no data on the developmental toxicity of the target substance Fatty acids, C16-18 (even numbered), stearyl esters (CAS 85536-04-5). The assessment was therefore based on studies conducted with analogue source 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).

CAS 22393-85-7

A combined repeated dose toxicity study with a reproduction/developmental toxicity screening test was performed according to OECD Guideline 422 under GLP conditions (key study, 2014) with Tetradecyl oleate (CAS 22393-85-7). No toxicologically relevant treatment related adverse effects were seen on viability, clinical signs, body weight, sex ratio, and gross pathology of F1 offspring. Based on these results, a developmental NOAEL of ≥ 1000 mg/kg was determined.

CAS 17671-27-1

A combined repeated dose toxicity study with a reproduction/developmental toxicity screening test was performed according to OECD guideline 422 under GLP conditions (supporting study, 2014) with Docosyl docosanoate (CAS 17671-27-1). No toxicologically relevant treatment related adverse effects were seen regarding viability, body weight, gross pathology, sex ratio, feeding, morphological examinations including behaviour observations of F1 offspring.Postural reflexes were determined on Day 1 postpartum in the pups. A significantly lower percentage of foetuses with positive response in the surface-righting reflex (righting reflex) at 1000 mg/kg bw was recorded compared to the control group. There were no treatment-related differences compared to the control animals at 100 or 300 mg/kg bw. The clinical relevance of this parameter remained unclear. Righting reflex was only assessed on Day 1 postpartum. The study report did not contain exact age matching of pups, nor considered biologically possible range of gestation length. No follow up behavioural testing at later time points during development of pups was done. Testing of righting reflex is not required following OECD GL 422.Therefore, a developmental NOAEL of ≥ 1000 mg/kg was determined based on the absence of toxicologically relevant effects.

Overall conclusion for effects on developmental toxicity

Analogue read-across from source substances was applied fordevelopmental toxicity.No toxicologically relevant effects on F1 offspring were observed in the available screening studies. The NOAEL for developmental toxicity was 1000 mg/kg bw/day.Based on the available data and following the analogue approach, absence of adverse effects on developmental toxicity can be expected for the target substance Fatty acids, C16-18 (even numbered), stearyl esters (CAS 85536-04-5).

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 Fatty acids, C16-18 (even numbered), stearyl esters (CAS 85536-04-5), 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 same results (no toxicity to reproduction and development) are expected for Fatty acids, C16-18 (even numbered), stearyl esters (CAS 85536-04-5). However, no final decision on classification for reproductive toxicity according to Regulation (EC) 1272/2008 can be made, as only information from a screening study is available.