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Description of key information

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The published data are considered as reliable with restrictions.
Qualifier:
no guideline followed
Guideline:
other: no data
Deviations:
not specified
GLP compliance:
not specified
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Housing and feeding:
Temperature: 20°C
Route of administration:
oral: feed
Vehicle:
not specified
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
2 years
Remarks:
Doses / Concentrations:
0, 0.3, 1.0 or 3.0% in the diet
Basis:
nominal in diet
No. of animals per sex per dose:
48 male and 48 female animals
Control animals:
yes, concurrent vehicle
Observations and examinations performed and frequency:
Body weight: 2-monthly intervals
Food and water consumption: 24-hour period prior to body weight determination
Blood (tail veins): week 15, 25 and 52
Blood (aorta): week 108
Urin: week 13, 24, 78
Sacrifice and pathology:
complete autopsy including histological examinations of tissues and organs
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
Water consumption and compound intake (if drinking water study):
no effects observed
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Details on results:
Body weight: High-dose male female rats weighed 7-8% lower than controls after 106 weeks.
Food consumption: Food consumption was 1-10% lower in all treated groups.
No other treatment related effects were observed.
The incidence of benign tumors and carcinomas of the thyroid, pituitary and peritoneal cavity were not statistically different from controls or fell within the spontaneous incidence rate of the Wistar rat.
Dose descriptor:
NOAEL
Effect level:
1 175 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male
Dose descriptor:
NOAEL
Effect level:
1 500 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
female
Critical effects observed:
not specified
Conclusions:
Groups of 48 male and 48 female rats were fed a diet containing 0, 0.3, 1.0 or 3.0% Quillaja extract for 108 weeks. Haematological examinations were made at week 15, 25, 52 and 108. Urinanalysis were carried out at week 13, 24 and 78. At sacrifice a complete autopsy including histological examination was performed.
High-dose male female rats weighed 7-8% lower than controls after 106 weeks and food consumption was 1-10% lower in all treated groups.
No other treatment related effects were observed.
The incidence of benign tumors and carcinomas of the thyroid, pituitary and peritoneal cavity were not statistically different from controls or fell within the spontaneous incidence rate of the Wistar rat. The NOAEL was 1175 mg/kg bw for males and 1500 mg/kg bw for females.
Executive summary:

Groups of 48 male and 48 female rats were fed a diet containing 0, 0.3, 1.0 or 3.0% Quillaja extract for 108 weeks. Haematological examinations were made at week 15, 25, 52 and 108. Urinanalysis were carried out at week 13, 24 and 78. At sacrifice a complete autopsy including histological examination was performed. High-dose male female rats weighed 7-8% lower than controls after 106 weeks and food consumption was 1-10% lower in all treated groups. No other treatment related effects were observed. The incidence of benign tumors and carcinomas of the thyroid, pituitary and peritoneal cavity were not statistically different from controls or fell within the spontaneous incidence rate of the Wistar rat. The NOAEL was 1175 mg/kg bw for males and 1500 mg/kg bw for females.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 500 mg/kg bw/day
Study duration:
chronic
Species:
rat
Quality of whole database:
4 studies with reliability of 2 are available.

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 - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Available data:

In a repeated dose study 15 male and 15 female CFE rats were fed diets containing 0, 0.6, 2 and 4% quillaja extract for 13 weeks. No abnormalities of behaviour or condition were seen. Bodyweight gain was reduced in the group receiving 4%. Food and water consumption were reduced in animals of each sex at all dietary levels but at the end of the study the weights of treated rats did not differ significantly from those of the controls.The relative liver weights of male rats given 2 or 4% quillaja was reduced and the stomach weight was increased in both sex at the same dose levels.

No effects on haematological parameters and clinical were noted.

Histopathology revealed no abnormal changes. Therefore the No Observed Effect Level was estimated as 400 mg/kg in male and female rats.

15 male and 15 female CFE rats were fed diets containing 0, 360, 1180 or 2470 mg/kg bw quillaja extract for males and 0,440, 1370 or 3030 mg/kg bw for females for 13 weeks.

No treatment-related effects on mortality, clinical signd, haematology, clinical chemistry, uirinanalysis gross pathology or histologic pathology were seen.

High-dose males and mid- and high-doese females had statistically significant lower body weight than those of controls. Food and water consumption was decreased in high- and mid-dose rats of both sexes. Liver weights were decreased in males at the 2.0 and 4.0& level, but since this was not correlated with changes in clinical chemistry the effects are considered as not resulting from toxicity of the test material. In addition, no related histopathological abnormalities were observed.

Therefore the No Observed Effect Level was estimated as 2470 mg/kg bw in male and 3030 mg/kg bw female rats.

Groups of 48 male and 48 female rats were fed a diet containing 0, 0.3, 1.0 or 3.0% Quillaja extract for 108 weeks. Haematological examinations were made at week 15, 25, 52 and 108. Urinanalysis were carried out at week 13, 24 and 78. At sacrifice a complete autopsy including histological examination was performed. High-dose male female rats weighed 7-8% lower than controls after 106 weeks and food consumption was 1-10% lower in all treated groups. No other treatment related effects were observed. The incidence of benign tumors and carcinomas of the thyroid, pituitary and peritoneal cavity were not statistically different from controls or fell within the spontaneous incidence rate of the Wistar rat. The NOAEL was 1175 mg/kg bw for males and 1500 mg/kg bw for females.

Groups of 48 male and 48 female mice were fed a diet containing 0, 0.1, 0.5 or 1.5% Quillaja extract for 84 weeks. Abnormal behaviour and condition were observed regularly and the body weight was determined at intervals. After 24, 56 and 84 weeks haematological parameters were measured.

No effects on mortality or clinical signs were observed. The body weights of the high-dose male animals were reduced. No changes in haematology were detected. The detailed autopsy and histopathology revealed no treatment-related abnormalities.

The No Observed Adverse Effect Levels was 700 mg/kg bw.


Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
The published data are reliable with restrictions.

Justification for classification or non-classification

In conclusion, the results of the available data on repeated dose toxicity indicate that Quillaja saponaria ext. does not need to be classified for repeated dose toxicity according to the CLP-Regulation (Regulation 1272/2008/EC) and therefore labelling is not necessary.