monoesters of C16 and C18 (branched and linear) fatty acids with decan-1-ol

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

Oral (OECD 422, rat): NOAEL fertility 300 mg/kg/day for females and 1000 mg/kg/day for males (read-across)

Link to relevant study records

Reference

Endpoint:

screening for reproductive / developmental toxicity

Type of information:

read-across from supporting substance (structural analogue or surrogate)

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

Key result

Dose descriptor:

NOAEL

Remarks:

systemic

Effect level:

300 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

female

Basis for effect level:

body weight and weight gain

food consumption and compound intake

Remarks on result:

other: Source: CAS 59231-34-4

Key result

Dose descriptor:

NOAEL

Remarks:

systemic

Effect level:

>= 1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male

Basis for effect level:

other: No adverse and treatment-related effects were observed up to and inlcuding the highest tested dose level.

Remarks on result:

other: Source: CAS 59231-34-4

Key result

Dose descriptor:

NOAEL

Remarks:

reproduction

Effect level:

300 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

female

Basis for effect level:

reproductive performance

Remarks on result:

other: Source: CAS 59231-34-4

Key result

Dose descriptor:

NOAEL

Remarks:

reproduction

Effect level:

1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male

Basis for effect level:

reproductive function (sperm measures)

Remarks on result:

other: Source: CAS 59231-34-4

Key result

Dose descriptor:

NOAEL

Remarks:

developmental

Generation:

F1

Effect level:

300 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

viability

body weight and weight gain

Remarks on result:

other: Source: CAS 59231-34-4

Key result

Reproductive effects observed:

yes

Lowest effective dose / conc.:

1 000 mg/kg bw/day (nominal)

Treatment related:

yes

Relation to other toxic effects:

reproductive effects as a secondary non-specific consequence of other toxic effects

Dose response relationship:

no

Relevant for humans:

no

Conclusions:

The available data on a suitable source substance CAS 59231-34-4 did not show any toxic effect on systemic toxicity or reproduction in males, therefore the NOAEL for reproduction and for systemic toxicity was ≥ 1000 mg/kg bw/day. In females, an increase in post-implantation loss, a decrease in the birth index and a decrease in the live birth index were determined at 1000 mg/kg bw/day. However, these effects were regarded as secondary non-specific consequence of adverse effects on food consumption and body weight (gain) in maternal animals at 1000 mg/kg bw/day. The NOAEL for systemic and reproduction toxicity was therefore set at 300 mg/kg bw/day for females. As explained in the analogue justification, this result is considered to be valid also for the target substance.

Effect on fertility: via oral route

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

300 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

The available information comprises adequate and reliable (Klimisch score 1) study from a reference substance 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 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.

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

Read Across Justification

There are no data on the reproduction toxicity of the target substance Monoesters of C16 and C18 (branched and linear) fatty acids with decan-1-ol. The assessment was therefore based on a study conducted with an analogue substance 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 (fertility)

CAS 59231-34-4

A combined repeated dose toxicity and reproduction/developmental toxicity screening study was performed according to OECD guideline 422 under GLP conditions (LPT, 2013). 10 rats/sex/dose were administered 100, 300 and 1000 mg/kg bw/day 8-methylnonyl (9E)-octadec-9-enoate (CAS 59231-34-4) in corn oil once daily, via oral gavage. The control group was exposed to the vehicle. Males were exposed from two weeks before mating on test day one until 35 days after mating. Females were exposed for up to 56 days (starting 2 weeks prior to mating up to at least day 3 of lactation).

No treatment-related parental effects were seen on mortality, clinical signs. Reduction in body weight (-9.4%) and food intake (-21.7%) was seen in high dose females during gestation/lactation.

No effects on water consumption, ophthalmology, haematological parameters, clinical chemistry parameters, macroscopic and microscopic pathology were observed. The NOAEL for parental systemic toxicity was 300 mg/kg/day for females and 1000 mg/kg bw/day for males.

No effects on the reproductive function of males (qualitative sperm staging) were observed. A statistically significant increase in post implantation loss, non-statistically significant decrease in birth index, elevated number of stillbirths, leading to a statistically significant reduction in the live birth index was observed in dams of the highest dose group. These effects were regarded as secondary non-specific consequence of adverse effects on food consumption and body weight (gain) in maternal animals at 1000 mg/kg bw/day.

The NOAEL for parental fertility was 300 mg/kg bw /day for females and ≥ 1000 mg/kg bw/day for males.

Overall conclusion for effects on fertility

Analogue read-across from the source substance 8-methylnonyl (9E)-octadec-9-enoate (CAS 59231-34-4) was applied for toxicity to reproduction (fertility). Based on the available data and following the analogue approach, no hazard for reproduction toxicity was identified for the target substance Monoesters of C16 and C18 (branched and linear) fatty acids with decan-1-ol.

Effects on developmental toxicity

Effect on developmental toxicity: via oral route

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

300 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

The available information comprises adequate and reliable (Klimisch score 1) study from a reference substance 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 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.

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

Developmental toxicity/teratogenicity

CAS 59231-34-4

In a combined repeated dose toxicity and reproduction/developmental toxicity screening study performed with 8-methylnonyl (9E)-octadec-9-enoate (CAS 59231-34-4) according to OECD guideline 422, the NOAEL for developmental toxicity was found to be 300 mg/kg bw per day. This NOAEL was based on effects on the viability and litter weight of foetuses seen in the highest dose group at 1000 mg/kg bw per day. The effects were regarded as secondary non-specific consequences of adverse effects on food consumption and body weight (gain) in maternal animals at 1000 mg/kg bw/day.

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 Monoesters of C16 and C18 (branched and linear) fatty acids with decan-1-ol, 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) No. 1272/2008. However, as no prenatal developmental toxicity study is available, the conclusion for classification is ‘data lacking’.