Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Repeated dose toxicity: oral

Currently viewing:

Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
Subacute Oral Toxicity of Polyglaycerol Ester
Author:
King, W.R., Michael, W.R., Coots, R.H.
Year:
1971
Bibliographic source:
Toxicology and Applied Pharmacology, 20, 327-333

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
Deviations:
yes
Remarks:
missing details on test material, no ophthalmologic or neurobehavioral examinations
GLP compliance:
no

Test material

Constituent 1
Reference substance name:
Decaoleic acid, decaester with decaglycerol
EC Number:
234-316-7
EC Name:
Decaoleic acid, decaester with decaglycerol
Cas Number:
11094-60-3
Molecular formula:
C210H382O31

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: mean: 72 g (males), 69 g (females)
- Housing: individually
- Diet (e.g. ad libitum): ad libitum (except for periods of urine collection)
- Water (e.g. ad libitum): ad libitum (except for periods of urine collection)


Administration / exposure

Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
continuously (except during urine collection)
Doses / concentrationsopen allclose all
Dose / conc.:
2.5 other: % in diet
Remarks:
approx. 950 mg/kg bw/d in males and 1300 mg/kg bw/d in females
Dose / conc.:
5 other: % in diet
Remarks:
approx. 1900 mg/kg bw/d in males and 2900 mg/kg bw/d in females
Dose / conc.:
10 other: % in diet
Remarks:
approx. 4100 mg/kg bw/d in males and 5200 mg/kg bw/d in females
No. of animals per sex per dose:
10
Control animals:
yes, sham-exposed

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: not specified

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: not specified

BODY WEIGHT: Yes
- Time schedule for examinations: weekly

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined: Yes

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time
-weighted averages from the consumption and body weight gain data: Yes

HAEMATOLOGY: Yes
- Time schedule for collection of blood: during fifth and eleventh week and from severed neck vessels at necropsy
- Anaesthetic used for blood collection: No data
- Animals fasted: No
- How many animals: all animals
- Parameters: Hemoglobin, Hematocrit, RBC count, WBC count, lymphocytes, neutrophils, monocytes, eosinophils

URINALYSIS: Yes
- Time schedule for collection of urine: during third and ninth week of the study
- Metabolism cages used for collection of urine: No data
- Animals fasted: Yes
- Parameters examined: total nitrogen, specific gravity and pH

NEUROBEHAVIOURAL EXAMINATION: Yes
- Dose groups that were examined: not specified

OTHER:
- collection of feces during fourth and tenth week for determination of total fatty acid (TFA) absorption
Sacrifice and pathology:
At the end of the 90-day period, each animal was killed by decapitation, a gross autopsy was performed and the testes or ovaries, adrenals, kidneys, spleen, liver, lung, heart, and brain were removed and weighed. Sections from these organs along with portions of the stomach, small intestine, urinary bladder, pancreas, esophagus, trachea, thyroid, mesenteric lymph node, and perirenal and epididymal fat were fixed in Bouin solution, mounted in paraffin, and stained with hematoxylin and eosin (H & E) for histologic examination.

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
Males fed PGE at the high dietary level (10 %) consumed more food and had a poorer feed efficiency value than did male control animals. However, these animals consumed enough food to maintain normal growth in spite of the decreased feed efficiency.
Food efficiency:
effects observed, treatment-related
Description (incidence and severity):
Males fed PGE at the high dietary level (10 %) consumed more food and had a poorer feed efficiency value than did male control animals. However, these animals consumed enough food to maintain normal growth in spite of the decreased feed efficiency.
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Description (incidence and severity):
Values from each sampling period generally fell within normal ranges (Burns and DeLannoy, 1966, Altman and Ditmer, 1964), and there were no indications of any blood disorder. Some values were significantly different from the SBO controls (P < 0.05); however, the differences were usually quite small and in no case established any trend or pattern indicative of a dose-related effect. As in the previous study (King et al., 1971), total
leukocyte counts obtained from tail blood in all groups were appreciably higher than corresponding values obtained from blood taken at necropsy. These data confirm those of Quimby and Goff (1952) that peripheral blood contains an increased number of luekocytes as compared to heart blood of rats.
Clinical biochemistry findings:
not examined
Urinalysis findings:
effects observed, treatment-related
Description (incidence and severity):
higher nitrogen excretion in females fed 10 % PGE, but no changes during the histologic examination of the urinary tract were found
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Description (incidence and severity):
Organ weights (both absolute and as a percentage of the body weight) were not remarkable, and there were no statistically significant differences (P > 0.05) between the SBO control and experimental groups
Gross pathological findings:
no effects observed
Description (incidence and severity):
At necropsy, the only gross observation of significance was what appeared to be very mild, chronic murine pneumonia in 18 ‘4 of the animals. The affected animals were scattered throughout all groups and the condition was not related to the feeding of PGE.
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
no effects observed
Description (incidence and severity):
Microscopic examination of the various organs and tissues confirmed the pneumonitis observed grossly but did not reveal any histopathologic changes interpreted as evidence of toxicity.
Histopathological findings: neoplastic:
no effects observed
Details on results:
It may be seen that the percentage of dietary fatty acids absorbed decreased as the level of PGE in the diet was increased. In all cases, fat absorption by animals fed PGE at the 5 and 10% dietary levels was significantly less than corresponding SBO control values. Absorption in animals fed the lowest level of the test material (2.5 %) was also less than that observed in the soybean oil-fed controls, but the differences were not uniformly significant. Values from animals in the group fed free oleic acid and glycerol fell between those of the 5 % PGE and SBO control groups.
Gas-liquid chromatographic (GLC) analyses of fecal fatty acids showed that excretion of oleic acid increased in a dose-related fashion : the oleic acid content of fecal fatty acids from animals fed the SBO control diet was 23 % compared to 32,41, and 51% when PGE was fed at levels of 2.5, 5.0, and lo%, respectively. It should be remembered that oleic acid (C,,l=) was the major fatty acid constituent (56 %) of the PGE product (Table 1). The increased excretion of fatty acids in general, and oleic acid in particular, shows that absorption of dietary PGE was not complete. The fecal oleic acid may have resulted from the excretion of intact PGE or from hydrolyzed or partially hydrolyzed but unabsorbed material. The oleic acid content of fecal fatty acids from animals fed free oleic and glycerol was 41x, corresponding exactly to the 5 % PGE group.

Effect levels

open allclose all
Dose descriptor:
NOEL
Effect level:
ca. 950 mg/kg bw/day (nominal)
Based on:
act. ingr.
Sex:
male
Basis for effect level:
other: decreased total fat absorption at 5 and 10%
Remarks on result:
other: 2.5% in diet
Dose descriptor:
NOEL
Effect level:
1 300 mg/kg bw/day (nominal)
Based on:
act. ingr.
Sex:
female
Basis for effect level:
other: decreased total fat absorption at 5 and 10%
Remarks on result:
other: 2.5% in diet

Target system / organ toxicity

Critical effects observed:
no

Applicant's summary and conclusion

Conclusions:
Polyglycerol ester (deca-glycerol deca-oleate) was fed to rats at dietary levels of 2.5, 5.0, and 10 % for 90 days. All animals appeared to be in excellent health throughout the study, and no adverse effects were found
upon survival, growth, organ weights, organ : body weight ratios, and hematologic values. There were no significant gross or microscopic tissue changesw hich could be attributed to dietary treatment.
Total fat absorption, as measured by fecal fatty acids, decreasedin a dose-related response. This resulted in a decreased utilization of feed by males fed PGE at the 10 % dietary level. These data show that absorption of
PGE was not complete.
Excretion of nitrogen in the urine by females fed PGE at the 10% dietary level was significantly greater than the control value during both the third and ninth collection periods. The reason for this difference is not understood
at the time of this study.