Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
16 June 2010 to 30 June 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study has been performed according to OECD and/or EC guidelines and according to GLP principles.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000; including the most recent partial revisions.
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
Name of test material (as cited in study report): Saccharomyces cerevisiae, Extract (Springer 0207/0-MG-L)
- Substance type: Light beige powder
- Physical state: Solid.
- Analytical purity: Not indicated by the sponsor; treated as 100% pure
- Lot/batch No.: 071002230
- Expiration date of the lot/batch: 31 May 2013
- Stability under test conditions: Stable under storage conditions
- Storage condition of test material: At room temperature in the dark
- Hygroscopic Yes, store in well-sealed container
- pH: 7.0 at concentration of 8%
- Stability at higher temperatures:Breakdown temperature > 100°C
- Stability in vehicle:
Propylene glycol: Unknown
- Solubility in vehicle:
Propylene glycol: Not indicated

Test animals

Species:
rat
Strain:
other: Crl:WI (Han)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: At start treatment the animals were 10 weeks old.
- Fasting period before study: no
- Housing: Individually housed in labeled Macrolon cages (MIII type, height 18 cm.) containing sterilized sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom).
- Diet (e.g. ad libitum): Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water (e.g. ad libitum): Free access to tap water.
- Acclimation period: at least 5 days before start of treatment under laboratory conditions
- Health inspection: A health inspection was performed prior to commencement of treatment, to ensure that the animals were in a good state of health. Special attention was paid to the skin to be treated, which was intact and free from any abnormality.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.9 – 21.5ºC
- Humidity (%): 39 - 75%
Temporary deviations from the minimum and maximum level of relative humidity occurred in the animal room. Laboratory historical data do not indicate an effect of the deviations.
- Air changes (per hr): approximately 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial light and 12 hours darkness per day.

IN-LIFE DATES: From: 16 June 2010 to 30 June 2010

Administration / exposure

Type of coverage:
occlusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
The formulation was applied in an area of approx. 10% of the total body surface, i.e. approx. 25 cm² for males and 18 cm² for females. The formulation was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D)*, successively covered with aluminum foil and Coban elastic bandage*. A piece of Micropore tape* was additionally used for fixation of the bandages in females only.
*. Manufacturers: Laboratoires Stella s.a., Liege, Belgium (surgical gauze) and 3M, St. Paul, Minnesota, U.S.A. (Coban & Micropore).

REMOVAL OF TEST SUBSTANCE
After 24 hours of application, dressings were removed and the skin cleaned of residual test substance using tap water.

TEST MATERIAL
- Dose level (volume): 2000 mg/kg (10 mL/kg) body weight
Duration of exposure:
24 h
Doses:
Single dosage, on Day 1.
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days.
- Observations:
Mortality/Viability: Twice daily.
Body weights: Days 1 (pre-administration), 8 and 15.
Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15.
Necropsy: At the end of the observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.
Statistics:
A dermal LD50 value was derived.

The results were evaluated according to:
- Globally Harmonized System of Classification and Labeling of Chemicals (GHS) of the United Nations (2007),
- Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008 on classification, labeling and packaging of substances and mixtures.
- EC criteria for classification and labeling of dangerous substances and preparations (Council Directive 67/548/EEC and all adaptations to technical progress and amendments of this Directive published in the Official Journal of the European Union).

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
Two males and two females showed chromodacryorrhoea on Day 1. In addition one male showed hunched posture on Day 1.

Brown staining was seen in the treated skin-area of all animals during the observation period. Two females showed scales or focal erythema in the treated skin-area during the observation period.
Body weight:
The changes noted in body weight gain in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
The dermal LD50 value of Saccharomyces cerevisiae, Extract (Springer 0207/0-MG-L) in Wistar rats was established to exceed 2000 mg/kg body weight.

Based on these results, Saccharomyces cerevisiae, Extract (Springer 0207/0-MG-L) does not have to be classified and has no obligatory labeling requirement for acute dermal toxicity according to the:
- Globally Harmonized System of Classification and Labeling of Chemicals (GHS) of the United Nations (2007),
- Regulation (EC) No 1272/2008 on classification, labeling and packaging of substances and mixtures,
- EC criteria for classification and labeling of dangerous substances and preparations (Council Directive 67/548/EEC and all adaptations to technical progress and amendments of this Directive published in the Official Journal of the European Union).
Executive summary:

Saccharomyces cerevisiae, Extract (Springer 0207/0-MG-L) was administered to five Wistar rats of each sex by a single dermal application at 2000 mg/kg body weight for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15). No mortality occurred. Two males and two females showed chromodacryorrhoea on Day 1. In addition one male showed hunched posture on Day 1. Brown staining was seen in the treated skin-area of all animals during the observation period. Two females showed scales or focal erythema in the treated skin-area during the observation period. The changes noted in body weight gain in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity. No abnormalities were found at macroscopic post mortem examination of the animals. The dermal LD50 value of Saccharomyces cerevisiae, Extract (Springer 0207/0-MG-L) in Wistar rats was established to exceed 2000 mg/kg body weight.