Registration Dossier

Administrative data

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 tetradecyl stearate (CAS 17661-50-6). The assessment was therefore based on studies conducted with analogue 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 analogue read-across approach is provided in the technical dossier (see IUCLID Section 13) and within Chapter 5.1 of the CSR.

CAS 22393-85-7

A combined repeated dose toxicity study and reproduction/developmental toxicity screening test, performed according to OECD 422 and GLP, is available (Rossiello, 2014). 10 rats/sex/dose were administered 100, 300 and 1000 mg/kg bw/day of tetradecyl oleate, formulated in carboxymethylcellulose (0.5% in purified water), once daily for at least 28 to 29 days (males) and up to 54 days (females) via gavage. The application started two weeks before mating on test Day 1 and ended on the day of, or one day before sacrifice. Day of sacrifice was on test Day 28 to 29 for the male rats and on Day 4 post-partum for the female rats, except for one single female, which was killed the day after the occurrence of total litter loss. The dose levels in the main study are based on the results of the dose range-finding study, in which 3 rats/sex/dose were administered 0, 100, 300 and 1000 mg /kg bw/day tetradecyl oleate for 14 days.

In the parental animals, no test item-related signs of toxicity were observed during the observational and neurological screenings. No differences of toxicological significance were seen in terminal body weight, body weight gain and in food consumption. No relevant changes were recorded in parental animals on clinical pathology investigations (haematology and clinical chemistry). Macroscopic inspection at autopsy and histopathological examination revealed no test item-related changes. The mating performance including the pre-coital interval and the copulatory evidence did not show any differences between groups. The resulting copulatory and fertility indices were 100% in all groups. All females were pregnant and had a comparable length of gestation. No variations were found in the number of corpora lutea and implantations between groups. All 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 control females had unilateral implantation. This finding was considered incidental since it was observed also in two control females. The litter size at birth and on Day 4 post-partum, as well as the mean litter and pup weights, was also similar between groups. Statistically significant increased mean group sex ratio for males was seen in high dose group on Day 4. No relevant findings were found in the pups at daily clinical observation or at post-partum examination. On the basis of the results obtained in the study, the NOAEL for systemic toxicity was considered to be ≥1000 mg/kg bw/day for males and females. The NOAEL for toxicity to reproduction was considered to be ≥1000 mg/kg bw/day for males and females.

 

Overall conclusion for effects on fertility

There are no available studies on the toxicity to reproduction and fertility of tetradecyl stearate. Therefore analogue read-across from 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 at 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 tetradecyl stearate 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
Prenatal developmental toxicity study (OECD 414), rat, oral:
NOAEL teratogenicity (F1) ≥ 1000 mg/kg bw/day
Additional information

Justification for read-across

There are no data on the developmental toxicity of tetradecyl stearate (CAS 17661-50-6). The assessment was therefore based on studies conducted with analogue 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 analogue read-across approach is provided in the technical dossier (see IUCLID Section 13) and within Chapter 5.1 of the CSR.

CAS 91031-48-0

A prenatal developmental toxicity study was performed according to OECD guideline 414, using fatty acids, C16-18, 2-ethylhexyl esters (CAS 91031-48-0) (Pittermann, 1994). Groups of 24 female Sprague-Dawley rats were administered the test substance in peanut oil at dose levels of 100, 300 and 1000 mg/kg bw/day by gavage during gestation days 6 to 15. On Day 20 of gestation the animals were euthanized and examined for maternal and foetal effects. No systemic effects were noted. No treatment-related effects were seen on the number of corpora lutea, implantation sites, pre-implantation loss, post-implantation loss, embryonic deaths, embryonic resorptions, foetal resorptions, and live foetuses. The examination of foetus litter size and weights, sex ratio and abnormalities (external, head, soft tissue and skeletal abnormalities) showed no differences between the control group and treatment groups and no indications of teratogenic effects. The NOAEL for developmental toxicity and teratogenicity in rats for Fatty acids C16-18, 2-ethylhexyl esters was considered to be ≥ 1000 mg/kg bw/day.

Overall conclusion on developmental toxicity

There are no available studies on the developmental toxicity of tetradecyl stearate. Therefore analogue read-across from a source substance was applied. The potential for developmental toxicity of the source substance fatty acids, C16-18, 2-ethylhexyl esters (CAS 91031-48-0) was assessed in a prenatal developmental toxicity study (OECD 414). The NOAEL value for developmental and teratogenicity was at the currently applied limit dose value of 1000 mg/kg bw/day. Therefore, no hazard to intrauterine development was identified. Based on the available data and following the analogue approach, the target substance tetradecyl stearate is considered to not affect intrauterine development.

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 tetradecyl stearate (CAS 17661-50-6) 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 and developmental toxicity 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.

Additional information