Yucca schidigera, ext.

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2019-04-17 - 2019-06-21

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

under GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2019

Report date:

2019

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

Acute Oral Toxicity-Acute Toxic Class Method, OECD Guideline for Testing of Chemicals No 423, Adopted: 17th December 2001

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Slovak National Accreditation Service

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Yucca schidigera, ext.

EC Number:

607-033-5

Cas Number:

223749-05-1

IUPAC Name:

Yucca schidigera, ext.

Test material form:

solid: particulate/powder

Remarks:

fine beige

Details on test material:

Storage: Room Temperature (20 ± 5 °C)
Homogeneity: homogeneous

Specific details on test material used for the study:

Storage: Room temperature (20 ± 5 °C)

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Slovak Academy of Sciences Dobrá Voda, Slovak Republic
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8-9 weeks
- Weight at study initiation: 201 - 209 g
- Fasting period before study: Animals were fasted 10-12 h prior to dosing (food but not water was withheld over-night).
- Housing: The animals were housed in plastic cages suspended on stainless steel racks, 3 animals per cage in a room equipped with central air-conditioning. Bedding was Lignocel S3/4, Lufa - ITL GmbH, Germany
- Diet (e.g. ad libitum): The laboratory food ssniff (ssniff Spezialdiäten GmbH, Germany) was available ad libitum.
- Water (e.g. ad libitum): The animals received tap water for human consumption. Supply of drinking was unlimited. The quality of drinking water is periodically analysed and recorded.
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): The average room temperature was maintained within the range of 22.30 ± 0.12 °C.
- Humidity (%): Relative humidity was maintained within 55.03 ± 1.37 %.
- Air changes (per hr): Room equipped with central air-conditioning, changes not denoted.
- Photoperiod (hrs dark / hrs light): The light regimen was set to a 12-hour light /12-hour dark cycle.

IN-LIFE DATES: From: 2019-04-17 To: 2019-05-10

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

water for injection

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 400mg/ml
- Amount of vehicle (if gavage): 5 ml/kg

MAXIMUM DOSE VOLUME APPLIED: 5 ml/kg

DOSAGE PREPARATION (if unusual): The required amount of the test item (according to the body weight and dose) was dissolved in vehicle (water for injection) shortly before administration.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The starting dose could be selected from the fixed dose levels of 5, 50, 300, and 2000 mg/kg body weight. A limit dose of 2000 mg/kg body weight was used as a starting dose because available information indicated that the test item was likely to be non-toxic regarding acute toxicity.

Doses:

2000 mg/kg

No. of animals per sex per dose:

3 + 3

Control animals:

other: not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed individually immediately after administration of the test item and 0.5, 1, 2, and 4 hours later. Each animal was inspected daily for the next 14 days.
Observations included: changes in skin, fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity, and behavioural pattern. Particular attention was given to potential neurologic endpoints such as tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
Individual weights of animals were measured immediately prior to administration of the test item and weekly thereafter. Weight differences after first and second weeks after administration were calculated and recorded.
- Necropsy of survivors performed: yes
All test animals were subjected to gross necropsy and the results were recorded for each animal. Examinations included: external body surface and orifices, the appearance of tissues and organs in the thoracic cavity (trachea, esophagus, heart, aorta, lungs with main stem bronchi, thymus, tracheobronchial lymph node) and in the abdominal cavity (liver, spleen, adrenal glands, kidneys, ovaries, uterus including cervix, urinary bladder, small intestine, large intestine, pancreas, stomach, mesenteric lymph nodes).
- Other examinations performed: clinical signs, body weight

Statistics:

not required

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50 cut-off

Effect level:

5 000 mg/kg bw

Based on:

test mat.

Mortality:

All (6/6 females) animals survived the limit dose of 2000 mg/kg body weight.

Clinical signs:

No mortality was observed during the study. During the follow up period, no animals displayed signs of intoxication, change of health, nor any other adverse reactions.

Body weight:

The body weights of all animals increased during the study. No body weight losses were observed between the first and second week after administration.

Gross pathology:

All animals were necropsied. During necropsy, no macroscopic findings were observed.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

LD50 cut-off = 5000 mg/kg

Conclusions:

The study was conducted under GLP according to OECD guideline 423 on the registered substance itself. The method is to be considered scientifically reasonable with no deficiencies in documentation. Hence, the results can be considered as reliable to assess the acute oral toxicity in rats.
The test item Yucca schidigera, ext. administered to 6 females at a limit dose of 2000 mg/kg body weight did not cause death. No signs of toxicity were observed during the first 4 hours in females or the 14-day observation period thereafter. The LD50 of the test item “Yucca schidigera, ext.” is greater than 2000 mg/kg body weight after single oral administration to Wistar rats.
Based on Annex 2d Test Procedure with a Starting Dose of 2000 mg/kg body weight of OECD Guideline 423 it can be concluded that the test item “Yucca schidigera, ext.” is according to GHS criteria classified in Category 5 or Unclassified with a LD50 cut off value equal to or greater than 5000 mg/kg body weight, after single oral administration to Wistar rats.

Executive summary:

The purpose of the study was to evaluate the potential toxic effect of the test item “Yucca schidigera, ext.” when administered as a single oral dose to Wistar rats.

The procedure according to OECD Guideline 423 Acute Toxic Class (ATC) method was used under GLP.

A limit dose of 2000 mg/kg body weight was used as a starting dose. The test item administered to 6 females at a limit dose did not cause death. During the observation period, no animals displayed signs of intoxication, change of health, nor any other adverse reaction.The body weights of all animals increased during the study. No body weight losses were observed between the first and second week after administration.During necropsy, no macroscopic findings were observed.

The LD₅₀ of the test item “Yucca schidigera, ext.” is greater than 2000 mg/kg body weight after single oral administration to Wistar rats.

Based on Annex 2d Test Procedure with a Starting Dose of 2000 mg/kg body weight of OECD Guideline 423 it can be concluded that thetest item “Yucca schidigera, ext.” is according to GHS criteria classified in Category 5 or Unclassified with a LD₅₀ cutoff value equal to or greater than 5000 mg/kg body weight, after single oral administration to Wistar rats.