Reaction mass of octadecyl heptanoate and octadecyl octanoate

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises an adequate and reliable study (Klimisch score 2 due to read-across) 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, ecotoxicological 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

Justification for read-across

There are no data on the reproduction toxicity of Reaction mass of octadecyl heptanoate and octadecyl octanoate (List No. 915-334-0). 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 structurally closest to the target substance is 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 analogue read-across approach is provided in the technical dossier (see IUCLID Section 13) and within Chapter 5.1 of the CSR.

Toxicity to reproduction

CAS 22393-85-7

A combined repeated dose toxicity and reproduction/developmental toxicity screening study was performed according to OECD guideline 422 under GLP conditions (Rossiello, 2014). 10 rats/sex/dose were administered 100, 300 and 1000 mg/kg bw/day Tetradecyl oleate (CAS 22393-85-7) 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, 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, precoital interval, and number of corpora lutea 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.

 

Overall conclusion for effects on fertility

There are no available studies on the toxicity to reproduction and fertility of Reaction mass of octadecyl heptanoate and octadecyl octanoate. Therefore read-across to a source substance was applied.

The potential for reproductive toxicity of the source substance Tetradecyl oleate (CAS 22393-85-7) was assessed in a reproductive/developmental screening study (OECD 422). The NOAEL value for fertility was defined to be higher than the currently applied limit dose value of 1000 mg/kg bw/day. Therefore, no hazard to reproduction was identified. Based on the available data and following the analogue approach, the target substance Reaction mass of octadecyl heptanoate and octadecyl octanoate is considered to not affect fertility.

Short description of key information:
Oral: OECD 422, rat, NOAEL fertility ≥ 1000 mg/kg bw/day
Oral: OECD 422, rat, NOAEL systemic ≥ 1000 mg/kg bw/day

Justification for selection of Effect on fertility 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).

Effects on developmental toxicity

Description of key information

Oral: OECD 422, rat, NOAEL development ≥ 1000 mg/kg bw/day
Oral: OECD 422, rat , NOAEL systemic ≥ 1000 mg/kg bw/day

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises an adequate and reliable study (Klimisch score 2 due to read-across) 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, ecotoxicological 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

Justification for read-across

Data on the reproduction toxicity of Reaction mass of octadecyl heptanoate and octadecyl octanoate (List No. 915-334-0) are not available. The assessment was therefore based on studies conducted with the analogue substance tetradecyl oleate (CAS 22393-85-7) 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 structurally closest to the target substance is 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 analogue read-across approach is provided in the technical dossier (see IUCLID Section 13) and within Chapter 5.1 of the CSR.

Developmental toxicity/teratogenicity

A combined repeated dose toxicity and reproduction/developmental toxicity screening study was performed according to OECD guideline 422 under GLP conditions (Rossiello, 2014). 10 rats/ sex/dose were administered 100, 300 and 1000 mg/kg bw/day Tetradecyl oleate (CAS 22393-85-7) 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).

The results of the offspring (viability) parameters pre-implantation loss, pre-birth loss, stillbirths, live births, cumulative pup loss on day 4 post-partum, litter size and pup weight were comparable between control and treatment group. Clinical signs of pups such as pallor, cold to touch, small and/or bruised muzzle, were observed in control and treatment groups and were therefore not considered to be of toxicological relevance. The number of male pups was significantly increased compared with the control group on Day 4 only. As the sex ratio (absolute percentage of males to females) was not significantly different from control, this is not considered to be a toxicologically relevant effect. The gross pathological examinations did not reveal any treatment-related effects. Based on the lack of effects, the NOAEL for developmental toxicity/teratogenicity is considered to be ≥ 1000 mg/kg bw/day.

Overall conclusion for developmental toxicity/teratogenicity

There are no available studies on the developmental toxicity and teratogenicity of Reaction mass of octadecyl heptanoate and octadecyl octanoate. Therefore read-across from a source substance was applied.

The potential for developmental toxicity and teratogenicity of the source substance Tetradecyl oleate (CAS 22393-85-7) was assessed in a reproductive/developmental screening study (OECD 422). The NOAEL value for developmental toxicity/teratogenicity was defined to be higher than the currently applied limit dose value of 1000 mg/kg bw/day. Therefore, no hazard to in utero development was identified. Based on the available data and following the analogue approach, the target substance Reaction mass of octadecyl heptanoate and octadecyl octanoate is considered to be not toxic to development.

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

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 Reaction mass of octadecyl heptanoate and octadecyl octanoate (List No. 915-334-0), data will be generated from data for a reference source substance 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 and development 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.

An OECD guideline 422 study will not provide evidence for definite claims of no reproduction/developmental effects. However, since no adverse effects on reproduction and development was noted up to and including the limit dose of 1000 mg/kg bw/day, the conclusion of no classification (conclusive but not sufficient for classification) is considered to be justified.