Fatty acids C16-18 (even numbered), mono and di esters with Sucrose

Endpoint summary

Description of key information

In the absence of data on repeated dose toxicity for the target substance Fatty acids C16 -18 (even numbered), mono and diesters with sucrose (no CAS) read-across approach was conducted on source substance Fatty acids C16 -18 (even numbered), mono, di and triesters with sucrose (no CAS) as explained in the analogue justification (see chapter 13) :

Oral (similar to OECD 408), rat, subchronic: NOAEL≥5% in diet (equivalent to 3240 mg/kg bw/day in males and 3430 g/kg bw/day in females)

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

sub-chronic toxicity: oral

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

Key result

Dose descriptor:

NOAEL

Effect level:

3 240 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male

Basis for effect level:

other: No adverse effects observed up to the highest dose tested.

Remarks on result:

other: Source: Sucrose ester MDT, Takeda, 1994, oral 13-weeks

Key result

Dose descriptor:

NOAEL

Effect level:

3 430 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

female

Basis for effect level:

other: No adverse effects observed up to the highest dose tested.

Remarks on result:

other: Source: Sucrose ester MDT, Takeda, 1994, oral 13-weeks

Key result

Critical effects observed:

no

Conclusions:

The NOAEL for the source substance was 5% in the diet (equivalent to 3240.0 and 3430.0 mg/kg bw/day in males and females, respectively). Therefore, the target substance is not expected to be toxic after subchronic exposure.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

3 240 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

The available information comprises an adequate and reliable study from a source 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 endpoint discussion for further details). The selected to study is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Data on the repeated dose toxicity ofFatty acids, C16-18 (even numbered), mono and diesters with sucrose (no CAS)are not available. The assessment was therefore based on studies conducted with an analogue substance Fatty acids, C16-18 (even numbered), mono di and triesters with sucrose (no CAS), 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).

Repeated dose toxicity, oral

Sub-chronic

Fatty acids, C16-18 (even numbered), mono di and triesters with sucrose

The oral toxicity of the test substance was determined in a 13-week feed study (Takeda, 1994) according to a protocol similar to OECD TG 408. The substance was added to the diet at 0, 1, 3, and 5%. Groups of 20 male and 20 female rats were tested at each dose level. After 13 weeks, the animals were sacrificed and necropsied. A slight mean increase in GPT activity of the medium and high dose males, and high dose females was noted. As all the observed values were within the control range, a longer term test would be needed to determine if this was treatment related. As there were no definitive treatment related effects, the NOAEL for both males and females was the highest dose, 5% of feed. For males, this was the equivalent of 3240 mg/kg bw/day, and for females 3430 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 toFatty acids, C16-18 (even numbered), mono and diesters with sucrose, data will be generated from data available for 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.

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