Reaction products resulting from esterification of sucrose with saturated C16-18 (even numbered) fatty acids

Carcinogenicity

Description of key information

The carcinogenetic potential of the test item was determined in a combined chronic and carcinogenetic oral study equivalent to OECD guideline 453. No substance related adverse effects were observed. The study demonstrated that the test substance was not carcinogenic in Fischer rats. According to this result the NOAEL of the carcinogenetic study was determined to be 1970 mg/kg bw/day.

Key value for chemical safety assessment

Carcinogenicity: via oral route

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:

Acceptable and well documented publication, similar to guideline

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

Dangerous Substance Directive (67/548/EEC)

The available study is considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is not considered to be classified for carcinogenicity under Directive 67/548/EEC, as amended for the 31st time in Directive 2009/2/EG.

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. As a result the substance is not considered to be classified for carcinogenicity under Regulation (EC) No 1272/2008, as amended for the sixth time in Regulation No 1297/2014.

Additional information

Chronic Toxicity and Carcinogenicity study in Fischer 344/DuCrj Rats 2000

The principal objective of this carcinogenetic testing study, of which the rat is the preferred test species, was to establish, under conditions of prolonged and repeated exposure, a general toxicological profile and assessment for the test substance (CAS 37318 -31 -3), permitting the determination of a maximum dose which produces no observed adverse effects through at least 24 months (NOAEL).

The substance was administered weekly in the feed of the Fischer rat (14 animals/sex/dietary level), at nominal dietary concentrations of 394, 1160 and 1970 mg/kg bw/day (males) and 480, 1440 and 2440 mg/kg bw/day (females). The feed mix was prepared twice during the study (1 week before the start of administration and 5 weeks later). Stability of the test item was checked after 3, 10 and 18 weeks by gas chromatographic analysis.

Body weight and food consumption determinations, as well as a detailed clinical examination of each animal, were conducted weekly throughout the study. Observations for moribundity and mortality were performed at least once daily. Physical examination was conducted weekly for signs of neoplasms.

Standard hematologic parameters were evaluated from blood from the orbital venous plexus every 6 months and from the inferior vena cava at the scheduled time of sacrifice.

Ophthalmologic exams were conducted on 10 male and female rats from each test group before initiation and on 10 rats of each sex from the control and the high-dose group before the end of treatment.

All animals placed on study were subject to a postmortem examination, which included (1) documenting and saving all gross lesions, (2) weighing designated organs, and (3) collecting representative tissue specimens for histopathologic evaluation. Animals scheduled for sacrifice at 52 or 104 weeks and moribund animals were exsanguinated from the abdominal aorta. All animals were necropsied completely.

Survival percentages for male animals in the control, low-medium- and high dose groups were 72, 68, 70 and 68 % (male) and 76, 70, 70 and 66 % (females).

Significant decrease in weight gain in male rats of the high-dose group relative to controls was observed in weeks 3 to 6 and weeks 8, 10 and 17 to 49 after administration.

The compound intake was clearly lower in the first week of administration in males of the high dose group and females of the medium and high dose groups relative to the respective controls.

Haematological examinations showed elevated MCV levels ( mean copuscular volume) relative to controls were observed in females 52 weeks (5 % group) 78 weeks (5%) and 104 weeks (5 %). In male groups elevated MCV and decreased MCHC (mean corpuscular hemoglobin conentration) were observed at 27 weeks (5%) 52 weeks (1, 3, 5%) and 78 weeks (MCV, 5%; MCHC, 1, 3 and 5%).

Absolute and relative spleen weights were higher than controls in males from the 3 and 5 % dose groups. The absolute heart weight was higher in the 5 % dose group. In females singnificant increases in absolute and relative spleen weight and absolute lung weight were observecd in the 3 % dose group but niot in the 5 % dose group.

In nonsurviving animals, approximately one-half of the animals in each group had large granular lymphocyte leukemia with associated macroscopic observations such as spleen enlargement and liver surface abnormalities.

Conclusion

The combined chronic/carcinogenetic (equivalent to OECD guideline 453) study demonstrated that the test substance was not carcinogenetic in Fischer rats. Differences in weight gain could be ascribed due to palatability. Hematology and clinical chemistry showed occasional statistical differences, but they were judged to be incidental. Leukemia and an associated increase in spleen weight were related to increased leukemia incidences in aging rats but not due to treatment. Based on this result the NOAEL was determined to be 1970 mg/kg bw/day.

Justification for selection of carcinogenicity via oral route endpoint:
Acceptable and well documented publication, similar to guideline