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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
25 June 2008 - 09 July 2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study was conducted according to OECD and EC guidelines and according to GLP principles.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report date:
2008

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
Details on test material:
- Name of test material (as cited in study report): S-500
- Physical state: yellow powder
- Lot/batch No.: MF1456-2345
- Expiration date of the lot/batch: 18 August 2011
- Storage condition of test material: At room temperature in the dark
- Stability under storage conditions: Stable

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: approx. 9 weeks old
- Weight at study initiation: males 260-295 g; females 182-200 g
- Fasting period before study: no
- Housing: Individually housed in labeled Macrolon cages (MIII type, height 18 cm) containing sterilized sawdust as bedding material and paper as cage-enrichment
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: Acclimatization period was 28 days before start of treatment under laboratory conditions.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.5 - 21.7
- Humidity (%): 42 - 89. Cleaning procedures in the room might have caused the temporary fluctuations above the optimal maximum level of 70% for relative humidity. Based on laboratory historical data, these fluctuations were considered not to have affected the study integrity.
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12


Administration / exposure

Type of coverage:
occlusive
Vehicle:
propylene glycol
Details on dermal exposure:
TEST SITE
- Area of exposure: 10% (25 cm² for males and 18 cm² for females)
- % coverage: 100 % coverage of the exposure area
- Type of wrap if used: surgical gauze patch, 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.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): the skin was cleaned of residual test substance using tap water.
- Time after start of exposure: 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit):
- Concentration (if solution): 2000 mg/kg (10 mL/kg) body weight

Duration of exposure:
24 hrs
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing:
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 of survivors performed: yes
- Other examinations performed: macroscopic examinations
Statistics:
None.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortality occurred.
Clinical signs:
Chromodacryorrhoea was noted in two males and one female between Days 1 and/or 2.
This symptom is occasionally seen in dermal toxicity studies. Based on the mild nature and short duration, this symptom was considered to be of no toxicological relevance.

Yellow staining on treated skin and/or several body parts was noted in all animals during the observation period. Scales were seen in the treated skin-area of one male and three females 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.
The incidence of slight body weight loss between days 1 and 8 in one female was considered not indicative of toxicity, based on the absence of any corroborative findings in these animals.

Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The dermal LD50 value of S-500 in Wistar rats was established to exceed 2000 mg/kg body weight.

Based on these results S-500 does not have to be classified and has no obligatory labeling requirement for dermal toxicity according to the Globally Harmonized System of Classification and Labeling of Chemicals (GHS) of the United Nations (2004) and EC criteria for classification and labeling requirements for dangerous substance and preparations (Council Directive 67/548/EEC).