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

Repeated dose toxicity: oral

Administrative data

Endpoint:

chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well documented publication, similar to guideline, a parallel satellite group was used in this combined chronic/carcinogenetic study to determine chronic effects.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 453 (Combined Chronic Toxicity / Carcinogenicity Studies)

Deviations:

no

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

α-d-Glucopyranoside, β-d-fructofuranosyl, octadecanoate

EC Number:

253-459-6

EC Name:

α-d-Glucopyranoside, β-d-fructofuranosyl, octadecanoate

Cas Number:

37318-31-3

Molecular formula:

C18 H36 O2 . x C12 H22 O11

Test animals

Species:

rat

Strain:

Fischer 344/DuCrj

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Japan Inc.
- Age at study initiation: 5 weeks old at the start of treatment
- Housing: Polycarbonate cages with hardwood chip bedding were used, and in each housed two animals.
- Diet: radiation-sterilized powder feed, CRF-1, Oriental Yeast Co., Ltd. ad libitum, replaced weekly, Feed mix was prepared twice during the study.
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature: 20-25 °C
- Humidity: 40-70 %
- Air changes: 12 changes/h
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: feed

Vehicle:

other: CRF-1

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS: Animals in groups of 14 rats/sex/group received the test item at 0, 1, 3 or 5 %.

DIET PREPARATION
- Rate of preparation of diet: The feed mix was prepared every 9 weeks.
- Storage temperature of food: Kept in a refrigerated storeroom.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Stability of the test substance in the mix was checked after 3, 10 and 18 weeks by gas chromatographic analysis.

Duration of treatment / exposure:

One year

Frequency of treatment:

Diet was replaced weekly

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 1, 3 or 5 % equivalent to 394, 1160, 1970 mg/kg bw/day (males) and 480, 1440 and 2440 mg/kg bw/day (females)
Basis:
nominal in diet

No. of animals per sex per dose:

Satellite group: 14 rats/sex/group were used

Control animals:

yes

Details on study design:

- Satellite group was used in this combined chronic/carcinogenetic study to determine chronic effects

Examinations

Observations and examinations performed and frequency:

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Checked daily

BODY WEIGHT: Yes
- Time schedule for examinations: once a week for the first 13 weeks and at least once every 4 weeks thereafter

FOOD CONSUMPTION AND COMPOUND INTAKE:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes

OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: Every 3 months and within 1 week before the end of treatment.
- Dose groups that were examined: In all animals before the administration, every 3 months and within 1 week before the end of treatment in the control and high-dose group.

HAEMATOLOGY: Yes
- Time schedule for collection of blood: every 3 month and at the scheduled time of sacrifice.
- Anaesthetic used for blood collection: No from the orbital venous plexus, Yes (sodium pentobarbital) from the inferior vena cava
- Animals fasted: Yes approximately 12 h

Sacrifice and pathology:

The following organs were weighed: liver, kidneys, adrenals, testes, ovaries, brain, heart, lungs, and spleen.
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes: brain, pituitary, thyroid (with parathyroids), thymus, trachea, lungs (including the bronchi), heart, aorta, salivary glands (submandibular and sublingual), liver, spleen, adrenals, pancreas, testes, epididymides, prostate gland, seminal vesicle, ovaries, uterus, vagina, skin (ventral region), tongue, esophagus, stomach (proventricular and glandular), duodenum, jejunum, ileum, cecum, colon, rectum, kidneys, bladder, lymph nodes (submandibular and mesenteric), mammary gland (female, ventral region), muscle (femoral muscle, either side), sciatic nerve (either side), femur (including the marrow, either side), sternum (including the marrow), eyes (including the optic nerves), Harderian glands (both), spinal cord (cervical, thoracic, and lumbar), and any other organs and tissues with macroscopic changes, nasal cavity, oviducts, auditory sebaceous gland, and extraorbital lacrimal gland.

Statistics:

Bartlett´s equal variance test
Analysis of variance (ANOVA)
Dunnett´s method
Scheffé´s method
Kruskal-Wallis H test
Amitage´s x^2 test
Fischer exact method

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

no effects observed

Haematological findings:

effects observed, treatment-related

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Gross pathological findings:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Details on results:

BODY WEIGHT AND WEIGHT GAIN: 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.

FOOD CONSUMPTION AND COMPOUND INTAKE: 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.

HAEMATOLOGY: Elevated MCV levels ( mean copuscular volume) relative to controls were observed in females in the satellite groups at 13 weeks (all dose groups) and 39 weeks (5 % group), 78 weeks (5%) and 104 weeks (5 %).

ORGAN WEIGHTS: The relative weight of lungs was increased in females from the high-dose group

GROSS PATHOLOGY: 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.

The effects described above were judged to be not based on compound related effects. The study demonstrated that the test substance was not toxic in Fischer rats.

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

2 440 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

female

Basis for effect level:

other: No adverse effects were observed

2

Dose descriptor:

NOAEL

Effect level:

1 970 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male

Basis for effect level:

other: No adverse effects were observed

Target system / organ toxicity

Critical effects observed:

not specified