Saccharomyces cerevisiae, lysate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 10 August 2017 to 7 November 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

Ambiant temperature (25.6°C) were outside of the expected ranges (19-25°C). There is a minor deviation

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Saccharomyces cerevisiae, lysate

EC Number:

305-230-8

EC Name:

Saccharomyces cerevisiae, lysate

Cas Number:

94350-12-6

IUPAC Name:

Saccharomyces cerevisiae, lysate

Test material form:

solid: particulate/powder

Remarks:

light beige

Details on test material:

- Source and lot/batch No.of test material:
supplied by the sponsor, batch no. AC17F00560
- Expiration date of the lot/batch: February 2019
- Purity test date: 30 June 2017

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Autolysat D100 batch AC17F00560
- Expiration date of the lot/batch: 02/ 2019
- Purity test date:30 June 2017

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature (15-25°C, =<70% relative humidity)
- Stability under test conditions: not applicable
- Solubility and stability of the test substance in the solvent/vehicle: not applicable

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: The test item was freshly formulated of 200 mg/mL in the vehicle on the day of administration. The formulation container was magnetic stirred continuously up to the end of dose administration procedures.

FORM AS APPLIED IN THE TEST (if different from that of starting material)
In formulation with ditilled water

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Crl:WI Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 12 or 13 days
- Weight at study initiation: 186-222g
- Fasting period before study: not specified
- Housing: Type II Propylene/polycarbonate
- Diet (e.g. ad libitum): ssniff® SM R/M "Autoclavable complete diet for rats and mice, ad libitum
- Water (e.g. ad libitum): tap water from the municipal supply, as for human consumption from a 500 ml bottle, ad libitum.
- Acclimation period: 9 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.6-25.6°C
- Humidity (%): 35-69% Relative Humidity
- Air changes (per hr): 15-20 air exchanges/hour
- Photoperiod (hrs dark / hrs light): 12 hours light/ 12 hours dark

IN-LIFE DATES: From: 3 August 2017 To: 30 August 2017

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL of test item in vehicle
- Amount of vehicle (if gavage): 10mL/kg
- Justification for choice of vehicle: not specified
- Lot/batch no. (if required): 63352Y25-2 (B. Braun Pharmaceuticals SA)
- Purity: not specified

MAXIMUM DOSE VOLUME APPLIED: 10mL/kg

DOSAGE PREPARATION (if unusual): The test item was freshly formulated at a concentration of 200 mg/mL in the vehicle. The formulation container was magnetic stirred continuously up to the end of dose administration procedures.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The initial dose level was selected to be that which is most likely to produce mortality in some of the dosed animals. In the lack of any preliminary toxicological information, 2000 mg/kg bw was selected to be the starting dose.

Doses:

2000 mg/kg bw.

No. of animals per sex per dose:

3 per group, 2 groups were used

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical signs : Clinical observations were performed on all animals at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter.
Body weight : The body weight was recorded on the day before treatment (Day -1), on the day of the treatment (Day 0), weekly thereafter and at necropsy (Day 14).
- Necropsy of survivors performed: yes
- Other examinations performed: . Individual observations were performed on the skin, fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Saccharomyces cerevisiae, lysate did not cause mortality at a dose level of 2000 mg/kg bw in any animal.

Clinical signs:

other: other: All animals were symptom-free during the observation period at a dose level of 2000 mg/kg bw.

Gross pathology:

There was no evidence of the macroscopic changes at a dose level of 2000 mg/kg bw in any animal.

Any other information on results incl. tables

CLINICAL OBSERVATIONS

DOSELEVEL:2000mg/kg bw, TreatmentonDay0                                                                                                             SEX:FEMALE

Cage No.

Animal Number

Observations

Observation days

Frequency

0

1

2

3

4

5

6

7-14

30'

1h

2h

3h

4h

6h

1

386

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

20/20

387

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

20/20

388

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

20/20

2

389

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

20/20

390

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

20/20

391

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

20/20

 

Remarks +=present

h=hours

‘ = minutes

Frequency of observation = number of occurrence of observation / total number of observations

 

BODY WEIGHT DATA

DOSELEVEL:2000mg/kg bw, TreatmentonDay0                                                                                               SEX:FEMALE

Cage No.	AnimalNumber	Body weight (g) Days				Body Weight Gain (g)
		-1	0	7	14	-1-0	0-7	7- 14	-1 - 14
1	386	230 232 228	215 222 213	245 258 245	266 285 250	-15 -10 -15	30 36 32	21 27 5	36 53 22
	387
	388
2	389	200 229 223	186 222 212	210 242 241	221 248 259	-14 -7 -11	24 20 29	11 6 18	21 19 36
	390
	391
Mean:		223.7	211.7	240.2	254.8	-12.0	28.5	14.7	31.2
Standarddeviation:		12.0	13.3	16.0	21.3	3.2	5.7	8.8	13.1

 

NECROPSY FINDINGS

DOSELEVEL: 2000mg/kg bw, TreatmentonDay0                                                                                                                                  SEX:FEMALE

Cage No.	Animal Number	Necropsy Date/ Necropsy Day	External Observations	Internal Observations	Organ/Tissue
1	386	29 August 2017 Day 14	No external observations recorded	No internal observations recorded	Not applicable
	387	29 August 2017 Day 14	No external observations recorded	No internal observations recorded	Not applicable
	388	29 August 2017 Day 14	No external observations recorded	No internal observations recorded	Not applicable
2	389	30 August 2017 Day 14	No external observations recorded	No internal observations recorded	Not applicable
	390	30 August 2017 Day 14	No external observations recorded	No internal observations recorded	Not applicable
	391	30 August 2017 Day 14	No external observations recorded	No internal observations recorded	Not applicable

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study, the acute oral LD50 value of the test item Saccharomyces cerevisiae, lysate was found to be above 2000 mg/kg bw in female Crl:WI Wistar rats.
According the GHS and the GHS-EU (CLP) criteria, classification of Saccharomyces cerevisiae, lysate can be ranked as "Not classified" for acute oral exposure.

Executive summary:

This GLP compliant study was performed according to OECD guideline 423 (Acute Toxic Class Method) in order to determine the acute toxicity after oral gavage on rats of the registered substance Saccharomyces cerevisiae.

Two groups of three female Crl:WI rats were treated with the test item at a dose level of 2000 mg/kg body weight (bw) (Group 1 and Group 2).

A single oral treatment was carried out by gavage for each animal after an overnight food withdrawal. Food was made available again 3 hours after the treatment. The test item was administered at the dose level of 2000 mg/kg bw.

Initially, three females (Group 1) were treated at a dose level of 2000 mg/kg bw. As no mortality was observed, a confirmatory group (Group 2) was treated at the same dose level. No mortality was observed in the confirmatory group.

Clinical observations were performed at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter. Body weight was measured on Days -1, 0, 7 and before necropsy (Day 14). All animals were subjected to a necropsy and a macroscopic examination.

Saccharomyces cerevisiae, lysate did not cause mortality  at  a  dose  level  of  2000 mg/kg bw.

All animals were symptom-free during the observation period at a dose level of 2000 mg/kg bw.

There were no treatment related body weight changes. Body weights were within the range commonly recorded for this strain and age.

There  was  no  evidence  of  the  macroscopic  changes   at   a   dose   level   of 2000 mg/kg bw.

Under the conditions of this study, the acute oral LD50 value of the test item Saccharomyces cerevisiae, lysate was found to be above 2000 mg/kg bw in female Crl:WI Wistar rats.

According the GHS and the GHS-EU (CLP) criteria, classification of Saccharomyces cerevisiae, lysate can be ranked as "Not classified" for acute oral exposure.