Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2009-01-27 to 2009-02-11
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study reliable without restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report Date:
2009

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
, adopted 1987-02-24
Deviations:
yes
Remarks:
, - Solid test substance was applied as a solution; - Humidity range (animal housing): 20- 80 %
GLP compliance:
yes (incl. certificate)
Remarks:
signed 2008-04-17
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Natriumsulfit wasserfrei food grade (E221)/(PRD30042389)
- Physical state: Solid / white
- Analytical purity: 98.1 %
- Batch No.: 83704888Q0
- Storage stability: The stability of the test substance under storage conditions over the test period was guaranteed by the sponsor, and the sponosr holds this responsibility.
- Storage condition of test material: Room temperature; under N2; protect against humidity
- Homogeneity: The test substance is homogenous by visual inspection.
No further information on the test material was stated.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: Young adult animals (male animals approx. 8 weeks, female animals approx. 12 weeks)
- Weight at study initiation: Animals of comparable weight (+/- 20% of the mean weight); mean weights males: 255 g; mean weights females: 218 g
- Housing: The animals were housed individually. The animals were housed in fully air-conditioned rooms. Type of cage: Makrolon cage, type III. Bedding: H 15005-29; Ssniff, Spezialitäten GmbH (Experimental Animal Diets Inc., 59494 Soest, Germany).
- Diet: VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany.
- Water (ad libitum): Tap water
- Acclimation period: At least 5 days before the beginning of the experimental phase; during the acclimatization period, the animals were accustomed to the environmental conditions of the study and to the diet
- Enrichment: NGM E-022; ABEDD®LAB & VET Service GmbH, Hasnerstraße 84/6; 1160 Wien - Austria

ENVIRONMENTAL CONDITIONS
- Temperature: 22 – 26°C
- Relative humidity: 20 – 80%
- Photoperiod (hrs dark / hrs light): 12/12
No further information on the test animals was stated.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
- Area of exposure: About 24 hours before administration the fur was clipped. Then a single application to the clipped epidermis (dorsal and dorsolateral parts of the trunk) was applied.
- % coverage: At least 10 % of the body surface (about 40 cm^2)
- Type of wrap: Covering of the application site with a semi-occlusive dressing (the bandage consists of four layers absorbent gauze, Ph. Eur. Lohmann GmbH & Co. KG and Fixomull stretch (adhesive fleece), Beiersdorf AG) for 24 hours, afterwards removal of the dressing.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Rinsing of the application site with warm water.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 10 ml/kg (application volume)
- Concentration: 20 g/100 ml
- Constant volume or concentration used: yes, constant volume
- For solids, paste formed: No, a solution was used for application. The test substanc epreparation was produced for the application group shortly before application by stirring with a magnetic stirrer.
VEHICLE: Doubly distilled water
No further information on the dermal exposure was stated.
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 males / 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Body weight determination: Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation.
- Signs and symptoms: Recording of signs and symptoms several times on the day of application, at least once each workday for the individual animals.
- Scoring of skin findings: Individual readings 30 – 60 minutes after removal of the semi-occlusive dressing (day 1), as a rule weekly thereafter and on the last day of observation.
- Mortality: A check for any dead or moribund animal was made twice each workday and once on weekends and on public holidays, these records are archived by Bioassay.
- Pathology: Necropsy with gross-pathology examination on the last day of the observation period after sacrifice with CO2 in a chamber with increasing concentrations over time.
Assessment of skin reactions: The evaluation of skin reactions was performed according to Draize, J.H. (1959): Appraisal of the safety of chemicals in foods, drugs and cosmetics. The association of food and drug officials of the United States Austin, Texas. Descriptions of any dermal findings not covered by this scale were recorded.
No further information on the study design was stated.
Statistics:
The means and standard deviation were calculated by using MS Excel 2003.

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
No systemic clinical observations were observed during clinical examination. No local effects were observed.
Body weight:
The mean body weights of the male animals increased throughout the study period. Mean body weights of the female animals decreased during the first post-exposure observation week, probably due to the bandage procedure, but increased during the second week.
Gross pathology:
No macroscopic pathologic abnormalities were noted in the animals (5 males and 5 females) examined on the last day of observation.
Other findings:
No data

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study the acute dermal median lethal dose (LD50) of Natriumsulfit wasserfrei food grade (E221) / (PRD 30042389) after dermal application was found to be greater than 2000 mg/kg body weight in male and female rats.
According to the criteria specified by Directive 67/548/EEC and subsequent regulations, the test item is not classified as acute toxic via the dermal route.
According to the EC Regulation No. 1272/2008 and subsequent regulations, the test item is not classified as acute toxic via the dermal route.