Oligo

Carcinogenicity

Description of key information

Oral (similar to OECD 453, read across), rat: NOAEL ≥ 1970 mg/kg bw/day

Key value for chemical safety assessment

Carcinogenicity: via oral route

Link to relevant study records

Reference

Endpoint:

carcinogenicity: 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.

Reason / purpose for cross-reference:

read-across source

Key result

Dose descriptor:

NOAEL

Effect level:

>= 1 970 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Remarks on result:

other: no treatment-related neoplastic findings up to and including the highest tested dose level of 1970 mg/kg bw/day.

Key result

Critical effects observed:

no

Conclusions:

The read across approach is justified in the analogue justification. The target and source substances are considered unlikely to differ in their repeated dose toxicity potential. The toxicity of the target substance is estimated based on an adequate and reliable combined chronic oral toxicity and carcinogenicity study with a structural analogue source substance. In a 2-year chronic feeding study (similar to OECD guideline 453) in male and female rats with the source substance Fatty acids C16-18 (even numbered), mono, di and triesters with sucrose (no CAS) no treatment-related neoplastic findings were found, up to and including the highest tested dose level of 5% in diet, which corresponds to 1970 mg/kg bw/day for male rats and 2440 mg/kg bw/day for female rats. Therefore, a NOAEL for carcinogenicity of ≥ 1970 mg/kg bw was derived for the target substance Fatty acids C16-18(even numbered), oligoesters with sucrose (no CAS).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 970 mg/kg bw/day

Study duration:

chronic

Species:

rat

Quality of whole database:

The available information comprises adequate and reliable (Klimisch score 2) studies from an analogue 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, eco-toxicological and toxicological profile. The selected studies are thus sufficient to fulfil the standard information requirements set out in Annex X, 8.9, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Carcinogenicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Carcinogenicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

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 Fatty acids C16-18(even numbered), oligoesters with sucrose (no CAS), 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.

Therefore, based on the read-across approach no carcinogenic potential is expected for Fatty acids C16-18(even numbered), oligoesters with sucrose (no CAS). Therefore, CLP/EU GHS criteria are not met, no classification required according to Regulation (EC) No 1272/2008.

Additional information

Read across justification

There are no data on the repeated dose toxicity of Fatty acids C16-18(even numbered), oligoesters with sucrose (no CAS). 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 analogue read-across approach is provided in the technical dossier (see IUCLID Section 13).

Repeated dose toxicity/carcinogenicity, oral, chronic

A combined chronic oral toxicity (14 rats/sex/dose for 52 weeks) and carcinogenicity study (50 rats/sex/dose for 104 weeks) was performed in Fischer 344/Du Crj rats similar to OECD guideline 453. The rats were fed a diet containing the source substance Fatty acids C16-18 (even numbered), mono, di and triesters with sucrose (no CAS) at 0, 1%, 3% or 5% in the diet, corresponding to 394, 1160, or 1970 mg/kg bw/day in males and 480, 1440 or 2440 mg/kg bw/day in females. Adequate observations, physical and ophthalmological examinations, body weight and food consumption recordings as well as haematological and clinical chemistry examinations were carried out throughout the study. Gross necropsy was performed on all animals at termination and organ weights were recorded for liver, kidneys, adrenals, testes, ovaries, brain, heart, lungs and spleen. Histopathological examinations were carried out on 48 tissues and organs in all control and high-dose animals and in animal tissues showing macroscopic changes in the low- and mid-dose groups. Based on the absence of treatment-related neoplastic effects, the NOAEL was found to be 5% in the diet, equivalent to 1970 mg/kg bw/day in males and 2440 mg/kg bw/day in females.

Based on the available data and following the analogue read across approach, no carcinogenic potential is expected for the target substance Fatty acids C16-18(even numbered), oligoesters with sucrose (no CAS).