Registration Dossier

Administrative data

Description of key information

Acute oral toxicity: The acute oral toxicity of the liquid QUILLAJA EXTRACT QL AGRI, LOTE: 260208-0700 was investigated according to US EPA Guideline EPA OPPTS 870.1100. A group of 3 female Sprague Dawley rats were administered a liquid extract of Quillaja saponaria at a single dose of 5000 mg/kg bw by gavage.
No mortality and no clinical signs of toxicity were obeserved. No abnormalities were recorded durcing necropsies. Therefore the acute oral LD50 value was estimated as > 5000 mg/kg bw.
Acute toxicity by the inhalation route: The acute toxicity by the the inhalation route of Quillaja saponaria powder was examined according to OECD Guideline 403. A limit test with an exposition of 0.45 mg/L as a nominal concentration was performed due to the physical-chemical properties of the test substance. This was the highest technical achievable concentration. A group of 5 males and 5 females received nasal only exposure to aerosol concentrations of the test substance during 4 hours. No mortality and clinical sign of toxicity were observed. No abnormalities were recorded during necropsy. Therefore the acute LC50 value of Quillaja saponaria powder can be stated as > 0.45 mg/l.
Acute dermal toxicity: The acute dermal toxicity of a liquid Quillaja saponaria extract was investigated according to US EPA Guideline EPA OPPTS 870.1200 (Acute Dermal Toxicity).
The test item was applied as a single dose of 2000 mg/kg bw to the shaved dorsal area of the trunk of 5 male and 5 female Sprague Dawley rats. The coverage of the exposed area was removed after 24 hours. No mortolatity or clinical signs of toxicity was observed. No abnormalites were recorded durcing necropsy. Therefore the acute dermal LD50 was estimated as > 2000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2008-05-09 - 2008-07-07
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Data obtained from a guideline study according to EPA OPPTS 870.1100 (Acute Oral Toxicity) and therefore considered reliable without restrictions.
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
up-and-down procedure
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
Test system: Sprague Dawley rats
Origin: Charles River Laboratories
Source: Facultad de Ciencias Vetcrinarias, Universidad de Buenos Aires, Av. Chorroarin 280, C1427CWO - Buenos Aires, Argentina.
Number of the test animals: 3 Animals. The test was conducted using a single sex (females). Females used were nulliparous and non-pregnant.

Age and weight at the start of the test: Young-adult animals of age 8-12 weeks old, 200-300 g
Body weight: The weight variation in animals used in the test didn t exceed 20% per cent of the mean weight.
Identification: Marks on the tail with inerasable ink
Acclimatization: Animals were acclimatized to laboratory conditions for 10 days before to the start of the test. After acclimatization healthy animals were randomized and assigned to treatment group.

Housing and feeding
Animals were housed under standard laboratory conditions. The experimental animals' room was provided with conditioned air filtered by HEPA filters with 10-15 air changes per hour. The temperature of the animals room was between 22 ± 3°C and the relative humidity between 30-70 per cent, although the upper range for humidity may have exceeded during the cleaning of the room.
Animals were provided with photoperiods of 12 hours light- 12 hours dark and placed into individual cages made of steel with litter of wood shavings.
The following diet was provided ad libitum: Balanced food Rat-Mouse Ganave supplied by Distribuidora Horacio Izaguirre.
Tap water dechlorinated by passage through cartridge of activated charcoal was used ad libitum.
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
Food was withheld the night prior to the administration of the test compound. For the administration of the dose, rigid probes with rounded end were used. The administration volume was 1 ml/100 gr.
After the administration of the test substance, animals were kept unfed for a 3 hour period. Once the substance was administered, observations were made and recorded systematically and individually for each animal.
Doses:
Limit Test 5000 mg/kg bw.
No. of animals per sex per dose:
3
Control animals:
no
Sex:
female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
none
Clinical signs:
none
Body weight:
The body weight was within the range of physiological variability of the test animals.
Gross pathology:
No abnormalities
Other findings:
none
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral toxicity of the liquid QUILLAJA EXTRACT QL AGRI, LOTE: 260208-0700 was investigated according to US EPA Guideline EPA OPPTS 870.1100. A group of 3 female Sprague Dawley rats were administered a liquid extract of Quillaja saponaria at a single dose of 5000 mg/kg bw by gavage.
No mortality and no clinical signs of toxicity were obeserved. No abnormalities were recorded durcing necropsies. Therefore the acute oral LD50 value was estimated as > 5000 mg/kg bw.
Executive summary:

The acute oral toxicity of the liquid QUILLAJA EXTRACT QL AGRI, LOTE: 260208-0700 was investigated according to US EPA Guideline EPA OPPTS 870.1100. A group of 3 female Sprague Dawley rats were administered a liquid extract of Quillaja saponaria at a single dose of 5000 mg/kg bw by gavage. No mortality and no clinical signs of toxicity were obeserved. No abnormalities were recorded durcing necropsies. Therefore the acute oral LD50 value was estimated as > 5000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
5 000 mg/kg bw
Quality of whole database:
One reliable study is available.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2002-04-08 - 2002-05-17
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Data obtained from a guideline study according to OECD guideline 403 and therefore considered reliable without restrictions.
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
fixed concentration procedure
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Test system: Rat Sprague Dawley, strain Crl: CD®(SD) IGS-BR
Origin: Charles River Laboratories
Source: FUCAL (breeders' of laboratory animals merger). Access North km. 42,5. Del Viso
Number of test animals: 10, 5 males and 5 females. The females were nulliparous and non-pregnant.
Weight and age at the star of the test: young adult rats, weighting 200-300 gr. The weight range within the test animal population did not exceed ± 20 per cent of the mean weight.
Acclimatization: The animals were acclimatized to the laboratory conditions for at least 9 days prior to the test. After the acclimatization, the healthy animals were randomized and assigned to groups of 5 per cage. (the same dosage and the same sex per cage).
HOUSING AND FEEDING CONDITIONS: The animals were housed under standard laboratory conditions.
The experimental animal room was provided with air conditioning, filtered by HEPA filters, with 10 to 15 air changes per hour. The temperature of the animal room was 22  3°C and the relative humidity 30-70 per cent, though the higher relative humidity range can be exceeded during the cleansing of the room.
Animals were provided with photoperiods of 12 hours light- 12 hours dark and placed into individual cages made of steel with litter of disposable diaper of daily replacement. The following diet were provided ad libitum: Ratas y Ratones, supported by Horacio Omar Gilardoni. Av. 25 de Mayo 167. San
Vicente, Buenos Aires, Argentina.
Drinking water dechlorinated by passage though cartridge of activated charcoal was used ad libitum.
Route of administration:
other: suspension in Tween 80 at 2% w/v
Type of inhalation exposure:
nose only
Details on inhalation exposure:
The exposure was performed in a 50L nasal chamber built for that Objective. The mixture of air and test substance was generated by a Dysem professional ultrasonic nebulizer (Argentine industry) joined to the inhalation chamber by a plastic tubing, to get 12 air changes per hour.
The extracted air of the chamber, was underwent to a treatment system that consisted on making it bubble in an solution of Sodium Hydroxide at 40%.
Slight negative pressure was maintained inside the inhalation chamber throughout the exposure period, by a compressor of air to diaphragm ENE free of oil (Equipos Neumáticos Especializados). The temperature, and the relative humidity were controled during the exposure.
Volumen of chamber: 50 L
Air changes per hour: 12
Stabilization time (min): 31
Nominal concentration (mg/L): 0.45
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
4 h
Concentrations:
The size of the particles was determined by a laser counter (Hand-Held Airborne particle counter- ABACUS 301).
The total amount of test substance (in mg) was divided by the total volume of air that flowed through the chamber to calculate the
nominal concentration of the test substance. 0.45 mg/l was the highest technical achievable concentration.
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
A group of 5 males and 5 females received nasal only exposure to aerosol concentrations of the test substance during 4 hours. After exposure, the residual test substance was removed from the face of each animal. Then they were returned to their corresponding cages, and food and water were not withheld.
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 0.45 mg/L air (nominal)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
no
Clinical signs:
none
Body weight:
The body weight was within the range of physiological variability of the test system.
Gross pathology:
No abnormalities were observed during necropsy.
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute toxicity by the the inhalation route of Quillaja saponaria powder was examined according to OECD Guideline 403. A limit test with an exposition of 0.45 mg/L as a nominal concentration was performed due to the physical-chemical properties of the test substance. This was the highest technical achievable concentration.
A group of 5 males and 5 females received nasal only exposure to aerosol concentrations of the test substance during 4 hours. No mortality and clinical sign of toxicity were observed. No abnormalities were recorded during necropsy.
Therefore the acute LC50 value of Quillaja saponaria powder can be stated as > 0.45 mg/l.
Executive summary:

The acute toxicity by the the inhalation route of Quillaja saponaria powder was examined according to OECD Guideline 403. A limit test with an exposition of 0.45 mg/L as a nominal concentration was performed due to the physical-chemical properties of the test substance. This was the highest technical achievable concentration. A group of 5 males and 5 females received nasal only exposure to aerosol concentrations of the test substance during 4 hours. No mortality and clinical sign of toxicity were observed. No abnormalities were recorded during necropsy. Therefore the acute LC50 value of Quillaja saponaria powder can be stated as > 0.45 mg/l.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
450 mg/m³
Quality of whole database:
One reliable study is available.

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2008-05-09 - 2008-07-08
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Data obtained from a guideline study according to US EPA Guideline EPA OPPTS 870.1200 (Acute Dermal Toxicity) and therefore considered reliable without restrictions.
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Test system: Sprague Dawley rats
Origin: Charles River Laboratories
Source: Facultad de Ciencias Veterinarias, Universidad de Buenos Aires. Av. Chorroarin 280, C1427CWO - Buenos Aires, Argentina
Number of the test animals: 10, 5 animals of each gender at each dose level. Females were nulliparous and non-pregnant.
Age and weight at the start of the test: Young-adult animals of age 8-12 weeks, with close body weight range. The weight variation in animals used in the test won't exceed ± 20% per cent of the mean weight.
Identification: Marks on the tail with inerasable ink
Acclimatization: Animals were acclimatized to the laboratory conditions during 11 days before to the start of the test. After acclimatization healthy animals were randomized and assigned to treatment I animal per cage.

Housing and feeding:
Animals were housed under standard laboratory conditions. The experimental animals' room was provided with conditioned air by HEPA filters with 10-15 air changes per hour. The temperature of the animals room was between 22 + 3°C and the relative humidity 30- 70 per cent, although the upper range for humidity may have exceeded during the cleaning of the room.
Animals were provided with photoperiods of 12 hours light- 12 hours darkness and placed into individual cages made of steel with litter of wood shavings.
The following diet was provided ad libitum: Balanced food Rat-Mouse Ganave supplied by Distribuidora Horacio Izaguirre.
Drinking water dechlorinated by passage through cartridge of activated charcoal were used ad libitum.
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Approximately 24 hours before treatment, the dorsal area of the trunk of the test animals was shaved, but taking care not to abrade the skin, since it could alter the test. Only healthy animals with intact skin were used.
The test substance was applied uniformly on the shaved area (approximately 10% of the total body surface area) using the graduated syringe.
The dressing was wrapped around the abdomen and was retained in place with non-irritant adhesive tape. The exposure period was 24 hours. Animals were not entirely immobilized. After the exposure period, the residues of the test substance were removed with water.
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
no
Clinical signs:
none
Body weight:
The body weight was within the range of physiological variability of the test animals.
Gross pathology:
No abnormalities were observed.
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal toxicity of a liquid Quillaja saponaria extract was investigated according to US EPA Guideline EPA OPPTS 870.1200 (Acute Dermal Toxicity).
The test item was applied as a single dose of 2000 mg/kg bw to the shaved dorsal area of the trunk of 5 male and 5 female Sprague Dawley rats. The coverage of the exposed area was removed after 24 hours. No mortolatity or clinical signs of toxicity was observed. No abnormalites were recorded durcing necropsy. Therefore the acute dermal LD50 was estimated as > 2000 mg/kg bw.
Executive summary:

The acute dermal toxicity of a liquid Quillaja saponaria extract was investigated according to US EPA Guideline EPA OPPTS 870.1200 (Acute Dermal Toxicity).

The test item was applied as a single dose of 2000 mg/kg bw to the shaved dorsal area of the trunk of 5 male and 5 female Sprague Dawley rats. The coverage of the exposed area was removed after 24 hours. No mortolatity or clinical signs of toxicity was observed. No abnormalites were recorded durcing necropsy. Therefore the acute dermal LD50 was estimated as > 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
One reliable study is available.

Additional information

No data gaps were identified. The available data are adequate for risk assessment and classification and labelling purposes.


Justification for selection of acute toxicity – oral endpoint
The available study is GLP-compliant and therefore considered reliable without restrictions.

Justification for selection of acute toxicity – inhalation endpoint
The available study is GLP-compliant and therefore considered reliable without restrictions.

Justification for selection of acute toxicity – dermal endpoint
The available study is GLP-compliant and therefore considered reliable without restrictions.

Justification for classification or non-classification

Acute oral toxicity:

The respective criteria are not met.

The estimated LD50 of > 5000 mg/kg bw. is well above the treshold for hazard category 4 (2000 mg/kg bw). Quillaja saponaria ext. is therefore not classified for acute oral toxicity.

 

Acute toxicity via the the inhalation route:

The respective criteria are met. The estimated LC50 of > 0.45 mg/l as highest technical achievable concentration does not justify the classification of the test item.

 

Acute dermal toxicity:

The respective criteria are not met.

The estimated LD50 of > 2000 mg/kg bw. is above the treshold for hazard category 4 (2000 mg/kg bw). Quillaja saponaria ext. is therefore not classified for acute dermal toxicity.