Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
7-Mar-2003 - 19-Sep-2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2003
Report Date:
2003

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
French Republic, Prime Minister, Interministerial Group on Chemicals (GIPC)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Physical state: white powder
- Analytical purity: 99.6%
- Lot/batch No.: 4673 and 5464
- Storage condition of test material: at room temperature, protected from humidity and under nitrogen gas.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Breeder: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: approximately 9 weeks
- Weight at study initiation: 290 ± 7 g for the males and 228 ± 6 g for the females
- Water and food: ad libitum
- Acclimation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 30 to 70
- Ventilation: approximately 12 cycles/hour of filtered, non-recycled air.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
- Area of exposure: a dorsal area of the skin (approximately 5 cm x 6 cm for the females and 5 cm x 7 cm for the males)
- % coverage: approximately 10%
- Type of wrap if used: hydrophilic gauze pad held in contact with the skin by means of an adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage.
Duration of exposure:
24 h
Doses:
A single dose of 2000 mg/kg of the test item in its original form was placed on a hydrophilic gauze pad (pre-moistened with 2 mL of PEG 400) and then applied to the clipped area of the skin.
No. of animals per sex per dose:
5
Control animals:
yes, concurrent no treatment

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:
> 1 000 - <= 2 000 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 798 - <= 1 596 mg/kg bw
Based on:
act. ingr.
Mortality:
At the 2000 mg/kg dose-level, all females were found dead or died on day 2. No clinical signs were observed prior to death in four of them and the last one was in coma prior to death.
Clinical signs:
At the 2000 mg/kg dose-level, in males, no clinical signs were noted. Dryness of the skin was recorded in 3/5 animals on day 3; it persisted, together with crusts, in one of them until day 7.
At 1000 mg/kg, no clinical signs were recorded. A very slight or well-defined erythema (grade 1 or 2), together with dryness of the skin in 3/5 animals, was observed in all females from day 4 up to day 8; some of these reactions persisted in 3/5 animals until day 10, 11 or 13.
Body weight:
A reduced body weight gain was seen in 4/5 females receiving the test item at the dose-level of 1000 mg/kg between day 1 and day 8. The body weight gain of the other animals was similar to that of CIT historical control animals.
Gross pathology:
Macroscopic examination of the main organs of the animals revealed no apparent abnormalities.

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
Under the experimental conditions, the dermal LD50 of NaTG is higher than 2000 mg/kg in male rats and is between 1000 and 2000 mg/kg in female rats.
Executive summary:

The test item was applied to the skin of one group of ten Sprague-Dawley rats (five males and five females).

The application was performed with the test item in its original form at the dose-level of 2000 mg/kg. Water was used to moisten the gauze pad and ensure a good contact with the skin. The test site was then covered by a semi-occlusive dressing for 24 hours.

Clinical signs, mortality and body weight gain were checked for a period of 14 days following the single application of the test item.

At the 2000 mg/kg dose-level, all females were found dead or died on day 2. No clinical signs were observed prior to death in four of them and the last one was in coma prior to death.

In males, no clinical signs and no mortality occurred. Dryness of the skin was recorded in 3/5 animals on day 3; it persisted, together with crusts, in one of them until day 7.

At 1000 mg/kg, no clinical signs and no mortality occurred. A very slight or well-defined erythema, together with dryness of the skin in 3/5 animals, was observed in all females from day 4 up to day 8; some of these reactions persisted in 3/5 animals until day 10, 11 or 13.

A reduced body weight gain was seen in 4/5 females receiving the test item at the dose-level of 1000 mg/kg between day 1 and day 8. The body weight gain of the other animals was similar to that of CIT historical control animals.

All animals were subjected to necropsy, but no apparent abnormalities were observed in any animal.