Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
20 November 1986 to 04 December 1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987
Report date:
1987

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))
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Trisodium 7-(4-(4-fluoro-6-(2-(2-vinylsulfonylethoxy)ethylamino)-1,3,5-triazine- 2-ylamino)-2-ureidophenylazo)naphthalene-1,3,6-trisulfonate
EC Number:
402-170-5
EC Name:
Trisodium 7-(4-(4-fluoro-6-(2-(2-vinylsulfonylethoxy)ethylamino)-1,3,5-triazine- 2-ylamino)-2-ureidophenylazo)naphthalene-1,3,6-trisulfonate
Cas Number:
106359-91-5
Molecular formula:
Hill formula: C26 H23 F N9 O13 S4 Na3
IUPAC Name:
trisodium 7-(4-(4-fluoro-6-(2-(2-vinylsulfonylethoxy)ethylamino)-1,3,5-triazine- 2-ylamino)-2-ureidophenylazo)naphthalene-1,3,6-trisulfonate
Details on test material:
- Name of test material (as cited in study report): FAT 40'224/C
- Description: powder
- Lot/batch No.: Op. 1/86; Vers. 10/86
- Expiration date of the lot/batch: October 1991
- Stabilityof test article dilution: stable for at least 2 hours
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch number of test material: Op. 1/86; Vers. 10/86
- Expiration date of the lot/batch: October, 1991

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Stability under storage conditions: Stable
- Stability under test conditions: stable for at least 2 hours

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, CH 4414 Fuellinsdorf/Switzerland
- Age at study initiation: 9 to 11 weeks
- Weight at study initiation: Males: 200 - 228 g; Females: 182 - 201 g
- Housing: Individually in Makrolon type-2 cages with standard softwood bedding ("Lignocel", Schill AG, 4132 Muttenz/Switzerland).
- Diet (e.g. ad libitum): Pelleted standard Kliba 343, Batch 57/86 rat maintenance diet ("Kliba", Klingentalmuehle AG, 4303 Kaiseraugst/Switzerland)
ad libitum.
- Water (e.g. ad libitum): Community tap water from Itingen, ad libitum.
- Acclimation period: At least one week under laboratory conditions after veterinary examination.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): 40-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
occlusive
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
4% in distilled water
Details on dermal exposure:
Approximately 24 hours before treatment, the backs of the animals were shaved with an electric clipper, exposing an area of approximately 10 % of the total body surface. On test day 1 the test article was applied evenly on the skin with a syringe and covered with an occlusive dressing. The dressing was wrapped around the abdomen and fixed with an elastic adhesive bandage. Twenty-four hours after the application, the dressing was removed. The treated skin was washed with luke-warm tap water and dried with disposable paper towels.

Application Volume/kg body weight: 4 mL at 2000 mg/kg
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Mortality/viability were checked four times during test day 1 and daily during days 2 - 15.
- Body weights were measured on test day 1 (pre-administration), 8 and 15.
- All animals were necropsied.
- Each animal had an examination for changes in appearance and behavior four times during day 1, and daily during days 2-15. All abnormalities were recorded. The following symptoms were checked: General behavior, respiration, eye, nose, motility, body position, motor susceptibility, skin, loss of weight.
Statistics:
The LOGIT-Model could not be applied to the observed rates of death. The toxicity was estimated without use of a statistical model.

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 was observed.
Clinical signs:
The application area was discolored. Discoloration of the treated skin was observed until termination of observation.
Body weight:
Emaciation (females) was observed.
Gross pathology:
No macroscopic organ changes were observed in any animal.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The dermal toxicity of FAT 40224/C was estimated to be: greater than 2000 mg/kg bw.
Executive summary:

In a GLP compliant dermal toxicity study, performed according to OECD guideline 402, Wistar rats (5/sex) were administered FAT 40224/C (2000 mg/kg bw). The test substance was dissolved in 4 % CMC in distilled water and applied on the skin with a syringe and covered with an occlusive dressing for 24 hours. The treated skin was washed after 24 h and a 14-day observation period followed. No mortality was observed during this period. The following symptoms were observed: Emaciation (females) and the application area was discolored. Discoloration of the treated skin was observed until termination of observation.


Based on the study results, the dermal median lethal dose (LD50) of the test substance was estimated to be: greater than 2000 mg/kg bw.