Registration Dossier

Administrative data

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
Additional information

In accordance with Regulation (EC) No 1907/2006, Annex VIII, 8.7.1 column 2, no test for reproductive toxicity is required as a pre-natal developmental toxicity study is available and included in the technical dossier.


Justification for selection of Effect on fertility via oral route:
In accordance with Regulation (EC) No 1907/2006, Annex VIII, Section 8.7.1 Column 2, no screening study for reproductive toxicity is required as a pre-natal developmental toxicity study is available and included in the technical dossier.

Effects on developmental toxicity

Description of key information
Oral (OECD 414), rat: 
NOAEL developmental toxicity: ≥ 900 mg/kg bw/day
NOAEL maternal toxicity: ≥ 900mg/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) from a reference substance with similar structure and intrinsic properties. Read-across is justified based on common functional group(s), common precursors/breakdown products and similarities in PC/ECO/TOX properties (refer to 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

There are no data for developmental toxicity available for Fatty acids, C16-18, 2-hydroxyethyl esters (CAS 97281-23-7). In accordance with Regulation (EC) No 1907/2006, Annex XI, 1.5 read-across from appropriate substances is conducted to fulfill the standard information requirements set out in Regulation (EC) No 1907/2006, Annex VIII, 8.7.

According to Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met”. In particular for human toxicity, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from structurally related substances (grouping or read-across) “to avoid the need to test every substance for every endpoint”.

 

Fatty acids, C16-18, 2-hydroxyethyl esters is an UVCB substance comprised of mainly mono- and diesters of ethylene glycol conjugated with C16 and C18 fatty acids. Thus, the test substance represents a glycol ester, which in general is known to be stepwise hydrolysed by gastrointestinal enzymes into the free fatty acid components and the respective alcohol (Long, 1958; Lehninger, 1970; Mattson and Volpenhein, 1972). Considering the common metabolism, the read-across approach is based on the presence of common precursors and the likelihood of common breakdown products via biological processes that result in structurally similar chemicals, and on common functional groups, structural similarities and similar physico-chemical, toxicological and toxicokinetic behaviour. For further details on the read-across approach, please refer to the analogue justification in section 13 of the technical dossier.

 

As no data are available on developmental toxicity, read-across to the analogue substance Fatty acids, C16-18, esters with ethylene glycol (CAS 91031-31-1) was conducted.

 

CAS 91031-31-1

Fatty acids, C16-18, esters with ethylene glycol was tested in an oral prenatal developmental toxicity studies according to OECD 414 in compliance with GLP (Pittermann, 1997).

Groups of 24 or 25 female rats per dose were dosed with the respective test compound via gavage from Day 6-15 post mating. Concurrent negative control groups receiving the vehicle alone were included.

Animals were dosed via gavage with 100, 300 and 900 mg/kg bw/day of Fatty acids, C16-18, esters with ethylene glycol. No mortalities in maternal animals and no compound-related symptoms were observed in the treatment groups. In addition, body weight and body weight gains were within the expected ranges. No compound-related differences were noted between the mean reproduction data of the test groups in comparison to the control group. At scheduled necropsy no macroscopic changes were noted in the dams of the treatment groups. Furthermore, pre-implantation loss, post-implantation loss, mean number of resorptions, embryonic deaths and total fetuses were not affected by treatment with the test substance. In addition, mean fetal placental and uterus weights were not affected. The fetal sex ratio was comparable in all groups and no treatment-related fetal abnormalities were found at necropsy. The examined fetuses showed no treatment-related malformations and the figures of visceral variations in the test groups were considered to be similar to the control group. The mean weight of live male and female fetuses in the mid-dose group was significantly increased, whereas the weights of live fetuses of the other treatment groups exhibited no significant differences. The figures of skeletal ossifications and variations showed no treatment-related deviations; thus various findings, all without dose-relationship, were considered to be incidental.

Based on the lack of adverse effects in this study, the NOAEL for maternal toxicity and developmental toxicity for rats was considered to be above 900 mg/kg bw/day.

 

Conclusion on developmental toxicity

The available data do not provide evidence that the source substance Fatty acids, C16-18, esters with ethylene glycol exhibits hazardous properties for in utero development. Therefore, no properties for developmental toxicity are expected for Fatty acids, C16-18, 2-hydroxyethyl esters (CAS 97281-23-7).

 

References

A detailed reference list is provided in the technical dossier (see IUCLID, section 13) and within the CSR.


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 (refer to the endpoint discussion for further details).

Justification for classification or non-classification

Based on the analogue read-across approach, the available data on developmental toxicity do not meet the classification criteria according to Regulation (EC) 1272/2008, and is therefore conclusive but not sufficient for classification.

No data for reproductive toxicity is required in accordance with Regulation (EC) No 1907/2006, Annex VIII, Section 8.7.1 Column 2.

Additional information