Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 12 September 2017 to 8 December 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 guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes

Test material

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: supplied by the sponsor, Batch/Lot Number: AC17F00560
- Expiration date of the lot/batch: February 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
The test item was administered as supplied in a single dose. Sufficient water was used to dampen the test material to ensure good contact with the skin.

Test animals

Species:
rat
Strain:
Wistar
Remarks:
Crl:WI Wistar rats
Sex:
male/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: Young adult rats
- Weight at study initiation: Between 216 g and 239 g
- Fasting period before study: not specified
- Housing: Type II. polypropylene/polycarbonate
- Diet (e.g. ad libitum): Animals received ssniff® SM R/M "Autoclavable complete diet for rats and mice – breeding and maintenance" produced by ssniff Spezialdiäten, 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: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.9–24.8°C
- Humidity (%): 30–66%
- Air changes (per hr): 15-20 air exchanges/hour
- Photoperiod (hrs dark / hrs light): 12 hours light (6.00 a.m. to 6.00 p.m.)

IN-LIFE DATES: From: 14 September 2017 To: 3 October 2017

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 5cm x 5cm (25cm²) on the back on the animals
- % coverage: approximately 10% area (and not less) of the total body surface
- Type of wrap if used: semi occlusive plastic wrap

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes
- Time after start of exposure: At the end of the exposure period, (after 24 hours of exposure period), the treated area of skin with the test item was washed with water at body temperature.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Concentration (if solution): not appliclble
- Constant volume or concentration used: no, adjusted to animal body weight
- For solids, paste formed: yes

VEHICLE
No vehicle was used. Only sufficient water was used to dampen the test material to ensure good contact with the skin
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 animals per sex per condition was used
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical observations were performed on the day of treatment at 1 and 5 hours after application of the test item and once each day for 14 days thereafter. Observations included the skin and fur, eyes and mucous membranes, the 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.
Adverse skin reactions at the site of application were recorded daily following the removal of the dressing.
The body weights were recorded on Day 0 (before the test item administration) and on Days 7 and 14 (before necropsy).
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
The test item did not cause mortality at the dose level of 2000 mg/kg bw.
Clinical signs:
other: other: There were no systemic clinical signs noted in any animal throughout the study. No adverse local dermal signs were observed after treatment with the test item or during the 14 days observation period.
Gross pathology:
There was no evidence of any gross macroscopic changes at a dose level of 2000 mg/kg bw.

Any other information on results incl. tables

TABLE1:            ClinicalObservations

 


DOSE LEVEL: 2000mg/kgbw        SEX:MALE

Cage No.

Animal No.

 

Observations

Observation days

 

Frequency

0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

1h

5h

1

1047

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

2

1048

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

3

1049

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

4

1050

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

5

1051

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16


DOSE LEVEL: 2000mg/kgbw                                                                                                             SEX: FEMALE

Cage No.

Animal No.

 

Observations

Observation days

 

Frequency

0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

1h

5h

6

1052

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

7

1053

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

8

1054

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

9

1055

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

10

1056

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

 

Remarks:

+ = present h = hour (s)

Treatment day = Day 0


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

 

TABLE2:     Body WeightData

 

DOSELEVEL: 2000mg/kgbw -  SEX MALE

 

Cage No.

Animal No.

Body weight (g)

Days

Body Weight Gain (g)

0

7

14

0-7

7-14

0-14

1

1047

233

299

363

66

64

130

2

1048

228

292

363

64

71

135

3

1049

224

275

344

51

69

120

4

1050

221

277

339

56

62

118

5

1051

239

303

372

64

69

133

Mean:

229.0

289.2

356.2

60.2

67.0

127.2

Standarddeviation:

7.2

12.7

14.0

6.4

3.8

7.7

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

DOSELEVEL: 2000mg/kgbw  - SEX: FEMALE             

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Cage No.

Animal No.

Body weight (g)

Days

Body Weight Gain (g)

0

7

14

0-7

7-14

0-14

6

1052

232

235

250

3

15

18

7

1053

216

229

242

13

13

26

8

1054

226

239

243

13

4

17

9

1055

234

247

258

13

11

24

10

1056

223

240

253

17

13

30

Mean:

226.2

238.0

249.2

11.8

11.2

23.0

Standard deviation:

7.2

6.6

6.8

5.2

4.3

5.5

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

TABLE3:            MacroscopicFindings

 

 

 

 

 

 

 

 

 

 

 DOSELEVEL: 2000mg/kgbw -SEX:MALE

 

Cage No.

Animal No.

Necropsy Date / Necropsy Day

External Observations

Internal Observations

Organ/ Tissue

1

1047

03 October 2017

Day 14

No external observations

No internal observations

Not applicable

2

1048

03 October 2017

Day 14

No external observations

No internal observations

Not applicable

3

1049

03 October 2017

Day 14

No external observations

No internal observations

Not applicable

4

1050

03 October 2017

Day 14

No external observations

No internal observations

Not applicable

5

1051

03 October 2017

Day 14

No external observations

No internal observations

Not applicable

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

DOSELEVEL: 2000mg/kgbw -SEX:FEMALE

Cage No.

Animal No.

Necropsy Date / Necropsy Day

External Observations

Internal Observations

Organ/ Tissue

6

1052

03 October 2017

Day 14

No external observations

No internal observations

Not applicable

7

1053

03 October 2017

Day 14

No external observations

No internal observations

Not applicable

8

1054

03 October 2017

Day 14

No external observations

No internal observations

Not applicable

9

1055

03 October 2017

Day 14

No external observations

No internal observations

Not applicable

10

1056

03 October 2017

Day 14

No external observations

No internal observations

Not applicable

 

 

 

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The acute dermal median lethal dose (LD50) of the test item Saccharomyces cerevisiae, lysate was found to be greater than 2000 mg/kg body weight in male and female Crl:WI rats.
According the GHS and the GHS-EU (CLP) criteria, classification of Saccharomyces cerevisiae, lysate can be ranked as "Not classified" for acute dermal exposure.
Executive summary:

The purpose of this GLP compliant study was to assess the potentiel acute dermal toxicity of the regiestered substance Saccharomyces cerevisiae, lysate on rats. This study was performed according to the OECD 402 guideline, limit dose test.

This study was performed with the test  item  Saccharomyces cerevisiae, lysate in male and female Crl:WI Wistar rats. A limit test was carried  out  at  2000 mg/kg  body weight  (bw)  in  both sexes  (5 rats/sex). The test item was applied as a single dermal 24-hour exposure followed by a 14-day observation period. Clinical observations were performed on all animals at 1 and 5 hours after dosing and daily for 14 days thereafter. Body weight was measured on Day 0 (prior to dosing) and on Days 7 and 14 (before necropsy). Gross macroscopic examination was performed on all animals at necropsy at the end of the 2-week observation period (Day 14).

Test item did not cause mortality at the dose level of 2000 mg/kg bw. There were no systemic clinical signs noted in any animal throughout the study. No adverse local dermal signs were observed after treatment with the test item or during the 14 days observation period. There were no treatment related effects on body weight or body weight gain during the observation period. There was no  evidence  of  any  macroscopic  changes  at  a  dose  level  of  2000 mg/kg bw.

The acute dermal median lethal dose (LD50) of the test item Saccharomyces cerevisiae, lysate was found to be greater than 2000 mg/kg body weight in male and female Crl:WI rats.

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